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CAS No. : | 619-73-8 | MDL No. : | MFCD00007376 |
Formula : | C7H7NO3 | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | JKTYGPATCNUWKN-UHFFFAOYSA-N |
M.W : | 153.14 | Pubchem ID : | 69275 |
Synonyms : |
|
Num. heavy atoms : | 11 |
Num. arom. heavy atoms : | 6 |
Fraction Csp3 : | 0.14 |
Num. rotatable bonds : | 2 |
Num. H-bond acceptors : | 3.0 |
Num. H-bond donors : | 1.0 |
Molar Refractivity : | 41.39 |
TPSA : | 66.05 Ų |
GI absorption : | High |
BBB permeant : | No |
P-gp substrate : | No |
CYP1A2 inhibitor : | No |
CYP2C19 inhibitor : | No |
CYP2C9 inhibitor : | No |
CYP2D6 inhibitor : | No |
CYP3A4 inhibitor : | No |
Log Kp (skin permeation) : | -6.34 cm/s |
Log Po/w (iLOGP) : | 1.28 |
Log Po/w (XLOGP3) : | 1.26 |
Log Po/w (WLOGP) : | 0.94 |
Log Po/w (MLOGP) : | 0.34 |
Log Po/w (SILICOS-IT) : | -0.49 |
Consensus Log Po/w : | 0.67 |
Lipinski : | 0.0 |
Ghose : | None |
Veber : | 0.0 |
Egan : | 0.0 |
Muegge : | 1.0 |
Bioavailability Score : | 0.55 |
Log S (ESOL) : | -1.85 |
Solubility : | 2.14 mg/ml ; 0.014 mol/l |
Class : | Very soluble |
Log S (Ali) : | -2.25 |
Solubility : | 0.87 mg/ml ; 0.00568 mol/l |
Class : | Soluble |
Log S (SILICOS-IT) : | -1.59 |
Solubility : | 3.92 mg/ml ; 0.0256 mol/l |
Class : | Soluble |
PAINS : | 0.0 alert |
Brenk : | 2.0 alert |
Leadlikeness : | 1.0 |
Synthetic accessibility : | 1.42 |
Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P273 | UN#: | N/A |
Hazard Statements: | H302-H412 | Packing Group: | N/A |
GHS Pictogram: |
* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
83% | at 80℃; Inert atmosphere | To a flame dried 150 mL pressure tube under argon was added Meldrum’s acid (5.00 g, 34.7 mmol) and anhydrous MeCN (40 mL). To the resulting solution was added p-nitrobenzyl alcohol (5.58 g, 36.4 mmol), the tube was tightly capped, and refluxed overnight. The reaction was concentrated under reduced pressure and purified with column chromatography (55/45 hexanes/EtOAc) to give 16a (6.86 g, 27.1 mmol) as an off-white solid in 83percent yield. A small crop of this material (1.00 g) was recrystallized from t-butanol/hexanes to give 16a (225 mg, 0.889 mmol) as a white solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
59% | With malonic acid; toluene-4-sulfonic acid In toluene | a) Preparation of mono-p-nitrobenzyl malonate by esterification of malonic acid with p-nitrobenzyl alcohol: A mixture of 27.5 g of p-nitrobenzyl alcohol, 28.1 g of malonic acid, 0.4 g of p-toluene sulfonic acid and 180 ml of toluene was heated to reflux (from 100° to 115° C.) for 6 hours in a 300 ml flask. During this period, the water formed was separated as the toluene azeotrope. The reaction mixture was cooled to room temperature, and thus formed precipitates were collected by filtration, washed with toluene and dried to give 48 g of crude mono-p-nitrobenzyl malonate (crude yield: 59percent, purity: 52.9percent) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97% | With triethylamine In dichloromethane at 0 - 20℃; for 3 h; | 4-Nitrobenzyl alcohol (1.53 g, 10 mmol) was introduced into a round bottomedflask, and dichloromethane (10 mNo. ) was added thereto. After the solution was cooledusing an ice bath, diketene (1.26 g, 15 mmol) was slowly added, and triethyknine(0.14 m-6 , 1 mmol) was added. This solution was warmed to room temperature, stirredfor 3 hours, and water (10 m-6 ) was added. The organic kyer was dried over MgSOand distilled under reduced pressure to give 4-nitrobenzyl acetoacetate (2.30 g,Yield=97percent). The resulting 4-nitrobenzyl acetoacelate was reacted according to thesame procedure as Example 1 to give the title compound in the yield of 68percent (2.09 g).1 H NMR(CDC1): 5 8.25(d, 2H), 7.53(s, 1H), 7.5l(d, 2H), 6.57(s, 1H), 5.27(s,32H), 4.21(s, 2H), 2.54(s, 3H)MS(M+1): 308 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97% | With indium(III) chloride; dimethylmonochlorosilane; benzil In dichloromethane at 20℃; for 24h; | |
95% | With Ph3P(+)-N(CO2Et)-N(-)-CO2Et; N-methoxylamine hydrochloride In tetrahydrofuran at 0℃; for 0.0833333h; | |
95% | Stage #1: 4-nitrobenzyl chloride With diisopropyl-carbodiimide In tetrahydrofuran at 100℃; for 0.0833333h; microwave irradiation; Stage #2: With acetyl chloride In tetrahydrofuran at 150℃; for 0.0833333h; microwave irradiation; Further stages.; |
95% | With 1-methyl-pyrrolidin-2-one; benzenesulfonyl chloride In 1,2-dichloro-ethane at 80℃; for 1.5h; | General procedures for the synthesis of alkyl chlorides General procedure: In a round-bottom flask, benzylic alcohol 1a (10 mmol, 2.0 equiv.), benzenesulfonyl chloride 2a (13 mmol, 1.3 equiv.) and NMP (2.5 equiv.). Then, DCE (3 mL) were added. The mixture was stirred at 80 C for 1.5 h. After completion of the reaction (monitoredby TLC), water (10 mL) was added and the mixture was extracted with ethyl acetate (3*10 mL). The combined organic phase was dried over anhydrous Na2SO4, filtered, and evaporated under reduced pressure. The crude product was purified by flash chromatography on silica gel to give the desired alkyl chlorides 3. |
94% | With 1,2,3-Benzotriazole; thionyl chloride In dichloromethane at 20℃; | |
94% | With 1-pyrrolidinecarboxaldehyde; 1,3,5-trichloro-2,4,6-triazine In acetone at 40℃; for 20.5h; Sealed tube; Green chemistry; | |
94% | Stage #1: 4-nitrobenzyl chloride With N,N-dimethylthiourea In dichloromethane at 20℃; Stage #2: With N-chloro-succinimide In dichloromethane at 20℃; for 2h; Irradiation; | |
93% | With benzoyl chloride; N,N-dimethyl-formamide In 1,4-dioxane at 0 - 40℃; for 24h; Sealed tube; | 4.4.2.6 Synthesis of 4-Nitrobenzyl chloride (28) General procedure: Entry 2: According to general procedure II (chapter 2.1.2) 4-nitrobenzyl alcohol 18 (2.00 mmol,1.0 equiv), DMF (15.5 ilL, 14.6 mg, 0.20 mmol, 10 mol%), dioxane (1 mL, 2 M) and BzCI (352 ilL,426 mg, 3.00 mmol, 1.5 equiv) were combined and stirred for 24 h at 40 °C. Purification as describedabove (mass crude material/5i02 1:13) delivered the product 29 as a colorless solid (319 mg,1.86 mmol, 93%). |
92% | With 1-pyrrolidinecarboxaldehyde; phenyl chloroformate In tetrahydrofuran at 20℃; chemoselective reaction; | |
90% | With oxalyl dichloride; Tropone In dichloromethane at 20℃; for 0.25h; Inert atmosphere; | |
81% | With 1,8-diazabicyclo[5.4.0]undec-7-ene; p-toluenesulfonyl chloride In dichloromethane at 0 - 20℃; for 0.166667h; | |
74% | With N-chloro-succinimide; potassium hexamethylsilazane; (1,3,4)-triphenyl-4,5-dihydro-1H-1,2,4-triazol-5-ylidene In dichloromethane at 20℃; for 6h; Inert atmosphere; | |
58% | With tungsten(VI) chloride In dichloromethane for 3h; Heating; | |
52% | With dmap; triethylamine; p-toluenesulfonyl chloride In dichloromethane at 0 - 15℃; for 12.5h; | |
With hydrogenchloride; zinc(II) chloride | ||
15 %Spectr. | With ziconium(IV) oxychloride octahydrate; lithium chloride In ethanol; water at 90℃; for 2h; | |
100 %Spectr. | With pyridine; thionyl chloride In dichloromethane | |
99 %Spectr. | With hexachloroethane In dichloromethane at 20℃; for 0.25h; Inert atmosphere; | General procedure for the chlorination of alcohols General procedure: In a 10 cm3 flask, 50 mg of phosphine-polyphosphazene(0.094 mmol) was dissolved in 3 cm3 anhydrous CH2Cl2 under an argon atmosphere. The resulting solution was cooled to 0 °C and a solution of 0.384 mmol C2Cl6 In a 10 cm3 flask, 50 mg of phosphine-polyphosphazene(0.094 mmol) was dissolved in 3 cm3 anhydrous CH2Cl2 under an argon atmosphere. The resulting solution was cooled to 0 C° and a solution of 0.384 mmol C2Cl6 in 1 cm3 anhydrous CH2Cl2 was added followed by 0.094 mmol ofthe alcohol after 5 min. After further stirring for 15 min the solvent was removed, the residue was taken up in a minimum amount of CHCl3 and the oxidized polymer was precipitated in an appropriate solvent. The polymer was removed by filtration, and washed with the precipitation solvent. The combined filtrates were evaporated to dryness and dried under high vacuum to yield the corresponding alkyl orbenzyl chlorides. in 1 cm3 anhydrous CH2Cl2 was added followed by 0.094 mmol ofthe alcohol after 5 min. After further stirring for 15 min the solvent was removed, the residue was taken up in a minimum amount of CHCl3 and the oxidized polymer was precipitated in an appropriate solvent. The polymer was removed by filtration, and washed with the precipitation solvent. The combined filtrates were evaporated to dryness and dried under high vacuum to yield the corresponding alkyl orbenzyl chlorides. |
317 mg | With 1-pyrrolidinecarboxaldehyde; benzoyl chloride In tert-butyl methyl ether at 40℃; for 24h; | |
With thionyl chloride Reflux; | ||
With thionyl chloride In dichloromethane for 12h; Reflux; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97.2% | Stage #1: 1-methyl-4-nitrobenzene With 2,2'-azobis(isobutyronitrile); chlorine at 120 - 130℃; Stage #2: With sodium acetate In toluene at 75 - 80℃; for 4h; Stage #3: With potassium hydroxide In methanol at 15 - 25℃; for 3h; | 4 1) 757.6 g (5.524 mol) of p-nitrotoluene was placed in a 1 L three-necked flask, and the mixture was heated to 120-130 ° C to be melted. 1.0 g of azobisisobutyl nitrile was added, stirred and passed through a chlorine gas for 4-6 h.During the reaction, the STI5000 high performance liquid chromatography (HPLC) sampling control was used to detect the content of the p-nitrobenzyl chloride by-product in the reaction mixture.At 0.9% (by weight), the chlorine was stopped, and then the stirring was continued for 2 hours.After liquid chromatography, after the reaction, the flaskIt contained 60.2% p-nitrobenzyl chloride, 38.9% p-nitrotoluene, 0.9% dichloro by-product, and the final product mixture weighed 865.2 g. 2) In a 500 ml four-necked flask, 300 ml of toluene is charged, and 68.4 g of the product mixture of the above step 1) is taken (including0.240 mol of p-nitrobenzyl chloride),It was added to toluene together with 20.1 g (0.245 mol) of anhydrous sodium acetate, and dissolved by stirring.The solution was warmed to 75-80 ° C with stirring and incubated for 4 hours.During the reaction, the STI5000 high performance liquid chromatography (HPLC) sampling control was used, and when the residual content of p-nitrobenzyl chloride in the reaction mixture was found to be 0.53% by weight, the reaction was stopped.The reaction mixture was cooled to 40 ° C, suction filtered, and the filtered sodium chloride solid was removed, and the filtrate was concentrated under reduced pressure and recovered.The toluene was recycled to give 74.2 g of a product mixture (0.240 mol of a mixture of p-nitrobenzyl acetate and p-nitrotoluene). 3) In a 500 mL three-necked flask, 74.2 g of the product mixture of the above step 2) and 360 ml of methanol were added, stirred to dissolve, and cooled to 15 °C.26.82 g of potassium hydroxide (0.478 mol) was added in four portions.Each time 6.70 g, 30 minutes apart, the temperature of the reaction solution was controlled to not exceed 25 °C. After the addition, stir for 1 hour.During the reaction, the STI5000 high performance liquid chromatography (HPLC) sampling control was used, and when the residual content of p-nitrobenzyl acetate in the reaction mixture was detected to be 0.04% by weight,The reaction was stopped and 3.3 g of formic acid was added dropwise to pH 8.The reaction mixture is concentrated under reduced pressure to recover a methanol cycleuse. After concentration, 200 mL of toluene was added, stirred and cooled to 5 ° C, suction filtered, and the filter cake was rinsed with a small amount of toluene.The filtrate was concentrated under reduced pressure to recover toluene, and the remaining filtrate was 22.37 g of p-nitrotoluene (containing a small amount of dichlorobenzene), which was recyclable. Wash with 100mL of ice waterThe filter cake was suction filtered and dried to give 35.72 g of p-nitrobenzyl alcohol as a pale yellow solid with a molar yield of 97.2% and a purity of 99.8%. |
30% | With sulfuric acid; fluorosulphonic acid; lead dioxide 1.) -20 deg C, 6 h, 2.) -50 deg C to -40 deg C; | |
With sulfuric acid; water; acetic acid Electrolysis; |
With sulfuric acid; lead dioxide | ||
durch elektrolytische Oxydation; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 91% 2: 93% | Stage #1: 4-nitrobenzaldehdye With potassium hydroxide In water at 20℃; Stage #2: With hydrogenchloride In water | |
90% | With sodium hydroxide In water at 30℃; for 5h; | |
1: 87% 2: 87% | With aluminum (III) chloride; triethylamine In dichloromethane at 20℃; for 48h; | General experimental methods for AlCl3-catalyzedCannizzaro/Tishchenko reactions General procedure: A mixture of AlCl3(0.5 mmol), the aldehyde (10 mmol),and triethylamine (5 mmol) was added to 2 cm3of driedCH2Cl2and stirred for 2 days at room temperature underargon atmosphere until the aldehyde was completelyconsumed. The reaction progress was probed by TLCand GC/MS (Agilent 6890 (GC)/5972A (MS)). The reactionmixture was then filtered through Whatman filterpaper (grade 2), and treated with sodium bicarbonatesolution, followed by isolating the organic phase via aseparatory funnel. The aqueous phase washed severaltimes with CH2Cl2to make sure that all organic materialsextracted. Then, the organic phase was dried usingsodium sulfate and subsequently analyzed by GC/MSand 1H NMR, and validated using melting or boilingpoint of the product. |
85% | With TEA; magnesium bromide In dichloromethane at 20℃; for 24h; | |
1: 42% 2: 36% | With N,N,N',N'-tetramethylguanidine In water at 100℃; for 0.5h; | |
1: 11% 2: 33% | With sodium hydroxide; 1,3-dimethylbenzimidazolium Iodide In methanol for 1h; Heating; | |
1: 33% 2: 11% | With sodium hydroxide; 1,3-dimethylbenzimidazolium Iodide In methanol for 1h; Heating; | |
1: 30% 2: 27% | With N,N,N',N'-tetramethylguanidine In water at 20℃; for 10h; | |
With sodium hydroxide at 40℃; | ||
In ethanol for 0.166667h; bain a ultrasons; Yield given. Yields of byproduct given; | ||
1: 38 (unit not given) 2: 34 <unit not given> | With aluminum oxide; Al2O3-acidic supported Na2S In cyclohexane at 80℃; for 24h; | |
In ethanol for 0.166667h; bain a ultrasons; Yield given. Yields of byproduct given; | ||
Stage #1: 4-nitrobenzaldehdye With triethylamine; lithium bromide at 20℃; for 48h; Stage #2: With water at 20℃; for 2h; Further stages.; | ||
With rat brain voltage-dependent potassium channel; NADP at 37℃; aq. phosphate buffer; Enzymatic reaction; | ||
With water; dimethyl sulfoxide; potassium hydroxide | ||
With tetrabutylammomium bromide; sodium hydroxide In toluene at 35℃; for 0.583333h; | 2.2.5. The side reaction of aldehyde in PTC system General procedure: A solution of TBAB (0.5 mmol), aldehyde (10 mmol) in toluene (30 mL) was placed in a 100 mL flask and stirred at 1400 rpm. 20 g of 50% (m/m) NaOH aqueous solution or 40 mmol of solid NaOH was added at 35°C. After the completion of the reaction as indicated by TLC, the aqueous phase was separated and washed twice with 5 mL of toluene. The pH value of the aqueous phase was adjusted to 2 with HCl solution. The resulting precipitate was filtered and rinsed twice with 3% HCl solution. The organic layer was washed with three 5 mL-portions of 3% HCl solution. Theorganic phase was dried over MgSO4 and evaporated to dryness.The crude products were purified by recrystallization from ethanol. | |
With novozyme 435 In aq. phosphate buffer at 30℃; for 24h; Enzymatic reaction; | General procedure for Novozyme 435 catalyzedredox reaction of p-nitrobenzaldehyde Reactions were performed in 2 ml reaction vessels. A solution of p- nitrobenzaldehyde (1 mM) in 100 mM sodium phosphate buffer, pH7.0, was shaken with 20 mg lipase at 30 C and 200 rpm. Aliquots were taken atdifferent points of time and analyzed by HPLC. Retention times of the peakswere matched with those of commercially available compounds; p-nitrobenzaldehyde (t R=7.5min), p-nitrobenzyl alcohol (t R=5min), p-nitrobenzoic acid (t R =6min). Experiments were done in duplicateand were found to have ± 5% error. | |
Stage #1: 4-nitrobenzaldehdye In neat (no solvent) for 0.0333333h; Green chemistry; Stage #2: With 1,4-diaza-bicyclo[2.2.2]octane In neat (no solvent) at 40℃; for 0.00416667h; Microwave irradiation; Green chemistry; | General procedure: In a 50 mL beaker, aldehyde (1 mmol) was roughly mixed with 1 g montmorillonite. After 2 min of mechanical stirring, DABCO (10 mmol) was added and then mixture was submitted into a single mode focused microwave reactor with continuous rotation for the time described in Table 1 (optimized time) at 40 °C. After completing the reaction (TLC), water (30 mL) was added to the mixture ,the product was washed by CH2Cl2(2×10 mL), clay was filtered, and the solvent was evaporated to give the alcohol component. To obtain the acid component, the filtrate was acidified, extracted with CH2Cl2, and dried over magnesium sulphate. Then the solvent was evaporated to givethe acid component.The solid clay portion was washed with methanol and dried at 120 °C under a reduced pressure to be reused in the subsequent reactions which showed the gradual decrease in the activity (Table 1). The filtrate was dried over MgSO4, the organic solvent was evaporated, and aryl alcohol was obtained. Isolated products were characterized by melting points, 1HNMR and 13C NMR spectrometric data and were compared with the literature and/or with authentic samples. | |
1: 47 %Spectr. 2: 45 %Spectr. | With N-butylacrylamide; 1,8-diazabicyclo[5.4.0]undec-7-ene; 3-quinuclidinol In 1,4-dioxane; water |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | With potassium borohydrate; hafnium tetrachloride In tetrahydrofuran at 40℃; for 17.1h; Inert atmosphere; Cooling with ice; | |
97% | With zirconium(IV) borohydride In tetrahydrofuran at 25℃; for 1h; | |
97% | With zinc borohydride pyridine complex In tetrahydrofuran for 2.3h; Heating; |
95% | With zinc borohydride pyridine complex In tetrahydrofuran for 2.2h; Heating; | |
94% | With chloro-trimethyl-silane; Benzyltriethylammonium borohydride In dichloromethane at 25℃; for 2.5h; | |
91% | Stage #1: 4-nitro-benzoic acid With 1-propanephosphonic acid cyclic anhydride; N-ethyl-N,N-diisopropylamine In ethyl acetate at 0℃; for 0.166667h; Stage #2: With sodium tetrahydridoborate In lithium hydroxide monohydrate; ethyl acetate at 0℃; for 0.416667h; | General procedure for the reduction of carboxylic acids to alcohols using T3P-NaBH4: General procedure: To a solution of carboxylic acid (10 mmol) in THF (10 mL), DIPEA (11 mmol, 1.42 mL) and 50% T3P in EtOAc (20 mmol, 6.36 mL) were added at 0 °C and the solution was stirred for about 10 min. Then aqueous solution of NaBH4 (10 mmol, 388 mg in 0.3 mL of H2O) was added to the reaction mixture at the same temperature and the reaction was allowed to stir till the completion of the reaction as indicated by TLC. After the completion of the reaction, the solvent was evaporated and the crude alcohol was extracted into EtOAc and the organic phase was washed with 5% citric acid (10 mL × 2), 5% Na2CO3 (10 mL × 2), water, and brine solution. The product was isolated after the evaporation of solvent under reduced pressure and dried over anhydrous Na2SO4. |
90% | With zinc(II) tetrahydroborate In tetrahydrofuran for 4h; Heating; | |
90% | Stage #1: 4-nitro-benzoic acid With sodium aminodiboranate In tetrahydrofuran at 20℃; Stage #2: With lithium hydroxide monohydrate | |
87% | With phenylsilane; C34H30CoO6; potassium mirror In tetrahydrofuran at 20℃; for 20h; Inert atmosphere; Schlenk technique; Glovebox; | |
82% | With diisopropoxytitanium(III) tetrahydroborate In dichloromethane for 4h; Ambient temperature; | |
79% | With tetra-N-butylammonium borohydride In dichloromethane Heating; | |
78% | With sodium tetrahydridoborate; Sodium sulfate [anhydrous]; dihydroxy(3,4,5-trifluorophenyl)borane In tetrahydrofuran at 20℃; for 10h; | |
73% | With whole cell cultures of dichomitus albidofuscus at 24℃; for 72h; Darkness; Microbiological reaction; | 2.5. general procedure for preparative biotransformation General procedure: The substrate (1 mmol) was added to submerged cultures of DAL on the 3rd culture day. The reaction mixture was incubated on an incubation shaker at 150 rmin 1 (deflection 25 mm) under exclusion of light at 24 °C for 4 days. 10 g of NaCl was added to media, and the mixture was stirred for 10 min at 800 rpm (magnetic stirrer). For extraction, 50 mL of Et2O was added, and the resulting mixture was stirred for 20 min at 800 rpm (magnetic stirrer), and centrifuged for 5 min at 3000 × g to separatethe organic layer. The extraction was repeated three times. The combined organic layers were washed with brine (1 × 30 mL) and water (1× 30 mL), dried over Na2SO4 and evaporated to dryness. The resulting reaction mixtures were analysed by GC/MS and NMR spectroscopy.Products were purified by column chromatography on silica gel (eluent(pentane/ether) changed gradually: 10/1, 7/3, 1/1) to isolate the majorcomponents. The respective fractions were combined, concentrated in vacuum, and the 1H and 13C NMR spectra of the residuals were compared with those of reference compounds. Every biotransformation was repeated three times to verify the reproducibility of the experiments. The detailed information about experimental data and yields is provided in the Electronic Supplementary Information. |
70% | Stage #1: 4-nitro-benzoic acid With 1,3,5-trichloro-2,4,6-triazine; potassium carbonate; triphenylphosphine In neat (no solvent) for 0.166667h; Green chemistry; Stage #2: With sodium tetrahydridoborate In neat (no solvent) for 0.0833333h; Green chemistry; | |
69% | With 4-methyl-morpholine; phenylsilane; Zinc acetate In toluene at 100℃; for 16h; Inert atmosphere; | |
65.5% | With potassium borohydrate; magnesium(II) chloride In tetrahydrofuran at 66℃; for 24h; | |
60% | Stage #1: 4-nitro-benzoic acid With benzotriazol-1-ol; N-[3-(N,N-dimethylamino)-propyl]-N'-ethyl-carbodiimide hydrochloride In dichloromethane at 20℃; for 0.5h; Stage #2: With sodium tetrahydridoborate; lithium hydroxide monohydrate In tetrahydrofuran at 0℃; for 0.5h; | |
With sodium tetrahydridoborate; diethylene glycol dimethyl ether; boron trifluoride diethyl ether complex | ||
With sodium tetrahydridoborate; aluminium(III) chloride; diethylene glycol dimethyl ether | ||
With sodium tetrahydridoborate; N,N-dimethylchloromethyleniminium chloride 1.) acetonitrile, THF, 0 deg C, 1 h; 2.) acetonitrile, THF, N,N-dimethylformamide, -78 deg C to -20 deg C, 2 h; Yield given. Multistep reaction; | ||
With zinc(II) tetrahydroborate; trifluoroacetic anhydride 1) 0-5 deg C, 15 min, 2) DME, rt, 48 h; Yield given. Multistep reaction; | ||
73 % Turnov. | With lithium aluminium hydride In diethyl ether at 0℃; for 1h; | |
Multi-step reaction with 2 steps 1: (C2H5)3N / tetrahydrofuran / 0.5 h / -7 °C 2: 83 percent / NaBH4, CH3OH / tetrahydrofuran / 1 h / 10 °C | ||
With sodium tetrahydridoborate In methanol at 0 - 20℃; for 2h; | ||
Multi-step reaction with 2 steps 1: neat (no solvent) / 30 °C / Inert atmosphere; Schlenk technique; Glovebox 2: mesoporous silica / methanol / 3 h / 60 °C / Inert atmosphere | ||
Multi-step reaction with 2 steps 1: sulfuric acid / 12 h / 25 - 70 °C 2: sodium tetrahydridoborate; lithium hydroxide monohydrate / ethanol / 1 h / 25 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97% | Stage #1: 4-nitrobenzyl chloride With 1,2,3-Benzotriazole; thionyl chloride In dichloromethane Stage #2: With potassium iodide In dichloromethane; N,N-dimethyl-formamide for 0.75h; | |
96% | With iodine In acetonitrile at 120℃; for 0.0666667h; Microwave irradiation; chemoselective reaction; | 4. 2. Typical Procedure for Iodinationof Alcohol General procedure: To a suspension of polymer-bound triphenylphosphine (1.2 mmol) in anhydrous acetonitrile (10 mL) were added iodine (1 mmol) and 1,6-hexanediol diol (1mmol). The reaction mixture was irradiated in microwave reactor at 120 °C for 3 min. The reaction mixture was filtered over a filter paper and washed with chloroform.The filtrate was extracted with aqueous sodium thiosulfate solution and dried with anhydrous sodium sulfate.The reafter, solvent was removed under reduced pressure to obtain 6-iodohexan-1-ol (30) in 93% |
96% | With iodine; triphenylphosphine In 4-(dicyanomethylene)-2-methyl-6-(p-dimethylaminostyryl)-4H-pyran at 20℃; for 2h; chemoselective reaction; | 2.2 General procedure for the iodination of alcohols General procedure: To a stirred solution of triphenylphosphine (1.5 mmol) in dry dichloromethane was added iodine (1.5 mmol)and polymer supported 4-DMAP (0.4 mmol, 40 mol%). Stirring was continued for 2 min; alcohol (1mmol) was then added. The reaction was monitored by TLC. After complete conversion of the alcohol (as indicated byTLC), the reaction was quenched with an aqueous solution of sodium thiosulfate (20 mL). The organic solventswere removed and the aqueous solution extracted with ethylacetate (50 mL). The combined organic layers weredried using sodium sulfate (anhydrous), filtered and concentrated. The residue was purified by column chromatography (2% EtOAc in hexane) to get the desired iodide product. |
93% | With polymethylhydrosiloxane; iodine In chloroform at 20℃; for 0.416667h; | |
91% | With boron trifluoride diethyl etherate; potassium iodide In 1,4-dioxane at 20℃; for 0.5h; | |
91% | With natural kaolinitic clay; sulfuric acid; potassium iodide for 0.1h; Irradiation; microwave; | |
89% | With Silphos; iodine In acetonitrile for 0.583333h; Heating; | |
85% | With boron trifluoride diethyl etherate; cesium iodide In acetonitrile at 20℃; for 0.5h; | |
85% | With toluene-4-sulfonic acid; potassium iodide for 0.0222222h; microwave irradiation; | |
85% | With aluminum(III) hydrogen sulfate; potassium iodide In hexane for 2h; Heating; | |
85% | With N-iodosaccharine; triphenylphosphine In acetonitrile for 1h; Heating; | |
80% | With iodine; triphenylphosphine for 0.0138889h; microwave irradiation; | |
80% | With phosphorus pentoxide; potassium iodide In acetonitrile at 20℃; for 2h; | General procedure for the iodination of alcohols using KI/P2O5 General procedure: To a mixture of alcohol (1.0 mmol) and KI (1.5 mmol, 0.25 g) in acetonitrile (5 mL), P2O5 (1.5 mmol, 0.23 g) was added and the reaction stirred at room temperature for the time specified in Table 2. After reaction completion (TLC or GC), the reaction mixture was filtered and the residue washed with ethyl acetate (3 × 8 mL). The combined organic layers were washed with an aqueous solution of Na2S2O3 (10%, 10 mL), water (10 mL), and dried over Na2SO4. The solvent was removed under reduced pressure to afford the corresponding product. If necessary, further purification was performed by column chromatography. |
78% | With 1H-imidazole; iodine; triphenylphosphine In toluene at 20℃; for 1h; | |
75% | With zirconium(IV) chloride; sodium iodide In acetonitrile at 20℃; for 1h; | |
73% | With potassium iodide In acetonitrile at 20℃; for 0.666667h; | |
69% | With cerium(III) chloride; sodium iodide In acetonitrile for 36h; Heating; | |
68% | With bis(1,5-cyclooctadiene)rhodium(I) trifluoromethanesulfonate; hydrogen; iodine; 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl In 1,2-dichloro-ethane at 20℃; Autoclave; Schlenk technique; | |
62% | With trimethylsilylphosphate; sodium iodide for 10h; Ambient temperature; | |
60% | With Amberlyst 15; sodium iodide In acetonitrile at 20℃; for 3.5h; | |
60% | With sulfuric acid; silica gel; potassium iodide In acetonitrile at 20℃; for 5h; | |
56% | With 1-methylimidazole hydrogen sulfate; sodium iodide at 20℃; for 0.583333h; Grinding; Neat (no solvent); chemoselective reaction; | |
50% | With KSF clay; sodium iodide at 60℃; for 5h; | |
50% | With triethylamine sulfate; potassium iodide for 0.0333333h; Microwave irradiation; Ionic liquid; | |
45% | With chloro-trimethyl-silane; sodium iodide In acetonitrile 0 deg C then up to r.t.; | |
45% | With dmap; triethylamine; p-toluenesulfonyl chloride; sodium iodide In dichloromethane | |
45% | With ziconium(IV) oxychloride octahydrate; sodium iodide In ethanol; water at 90℃; for 0.5h; | |
38% | Stage #1: 4-nitrobenzyl chloride With sodium tetrahydroborate In 1,4-dioxane at 80℃; for 0.5h; Inert atmosphere; Stage #2: With iodine In 1,4-dioxane at 60℃; for 24h; Inert atmosphere; Sealed tube; | 11 Example 11, 4-Nitrobenzyl iodide (R=NO2 in structural formula II) In a 25 mL reactor under nitrogen, add sodium borohydride (19.0 mg, 0.5 mmol), 4-nitrobenzyl alcohol (76.6 mg, 0.5 mmol) and 1,4-dioxane (1 mL) in sequence, Heat to 80°C, keep it for 0.5 hours and then cool to room temperature, add iodine granules (126.9mg, 0.5mmol), seal the reactor, and react at 60°C for 24 hours. After the reaction system was cooled to room temperature, 5 mL of water and 5 mL of ethyl acetate were added dropwise and stirred for 10 min, and then extracted twice with 10 mL of ethyl acetate, and the organic phases were combined. Dry with anhydrous sodium sulfate for 0.5 h, filter, and rotatory-evaporate the organic phase to obtain a crude product. Crude product is separated with petroleum ether: ethyl acetate = 5:1 as eluent, 200-300 mesh neutral silica gel column adsorption phase column chromatography to obtain a white solid product with purity greater than 99% 4-nitrobenzyl iodide 50.0mg , The isolated yield is 38%. |
With 1H-imidazole; iodine; triphenylphosphine In diethyl ether; acetonitrile for 1.5h; | ||
With dmap; iodine; triphenylphosphine In dichloromethane at 20℃; for 2h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With Zn(BH4)2(Ph3P)2 In tetrahydrofuran at 20℃; | |
100% | With N-methylpyrrolidine zinc borohydride In tetrahydrofuran at 20℃; for 0.583333h; | |
98% | With poly-η-(pyridine)zinc borohydride In diethyl ether for 6h; Ambient temperature; |
98% | With Zr(BH4)2Cl2(dabco)2 In tetrahydrofuran for 1.7h; Heating; | |
98% | With 1,3-propanediylbis(triphenylphosphonium) tetrahydroborate In acetonitrile at 20℃; for 0.0833333h; | 3.5. General experimental procedure for reduction of aldehydes, ketones and benzoyl chlorides to corresponding alcohols by III in acetonitrile General procedure: To the stirring solution of aldehyde (1 mmol) in CH 3 CN (5 mL) in a round-bottom flask (25 mL) the reducing agent III (1 mmol) was added. The resulting mixture was stirred at room temper- ature. Progress of the reaction was monitored by TLC (Eluent; n-hexane/ethyl acetate: 10:3). After completion of the reaction, CH 3 OH (3 mL) was added to the mixture and stirred for an addi- tional 1 h. The solvent was evaporated, and the crude product was purified by chromatography on a silica gel plate (TLC silica gel 60 G F 2 5 4 25 glass plates 20 ×20 cm). |
97% | With diisopropoxytitanium(III) tetrahydroborate In dichloromethane at -20℃; for 0.133333h; | |
95% | With 1-benzyl-1-azonia-4-azabicyclo[2.2.2]octane tetrahydroborate In acetonitrile for 2h; Heating; | |
93% | With zinc(II) tetrahydroborate; N,N,N,N,-tetramethylethylenediamine In tetrahydrofuran; diethyl ether at 0℃; for 0.25h; | |
93% | With zinc(II) tetrahydroborate; N,N,N,N,-tetramethylethylenediamine In tetrahydrofuran; diethyl ether at 0℃; for 0.25h; | |
93% | With butyltriphenylphosphonium tetrahydroborate In dichloromethane at 20℃; for 0.0833333h; | |
93% | With sodium tetrahydroborate; lithium perchlorate In acetonitrile for 0.5h; | |
91% | With methyltriphenylphosphonium tetrahydroborate In dichloromethane | |
90% | With Ν,Ν-dimethylethylamine alane In tetrahydrofuran; toluene at 0℃; for 0.5h; | |
With methanol; methyltriphenylphosphonium tetrahydroborate 1) CH2Cl2, room temperature, 2) 1.5 h; Yield given. Multistep reaction; | ||
With (1,4-diazabicyclo{2.2.2}-octane)zinc(II) tetrahydoborate In tetrahydrofuran for 20h; Heating; Yield given; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With bismuth(III) chloride for 1.25h; Heating; | |
98% | With K5<CoW12O40> for 0.75h; Heating; | |
97% | With potassium fluoride at 80℃; for 3h; |
96% | at 116℃; for 10h; | |
96% | With 1-methyl-3-butylimidazolium hydrogen sulfate-impregnated propylsulfonic acid-functionalized mesoporous silica SBA-15 at 25 - 30℃; for 40h; Neat (no solvent); | |
95% | With iron(III) chloride at 20℃; for 6h; | |
95% | With cobalt(II) chloride at 60℃; for 2.2h; | |
92% | With cerium(IV) trifluoromethanesulfonate at 20℃; for 0.1h; | |
90% | Stage #1: acetic acid With 2,2,4,4,6,6-hexachloro-1,3,5-triaza-2,4,6-triphosphorine In neat (no solvent) at 20℃; for 0.0166667h; Stage #2: 4-nitrobenzyl chloride In neat (no solvent) at 20℃; for 0.133333h; | Generalprocedure for the preparation of esters 3a-n General procedure: A mixture of carboxylic acid (1 mmol) and TAPC (0.5 mmol, 0.17 g) was prepared in a mortar. The mixturewas ground with a pestle for 1 min. Then alcohol (1 mmol) was added to thereaction mixture and grinding was continued at room temperature for appropriatereaction times indicated in Table 1. After completion of the reaction(monitored by TLC), H2O (10 mL) was added to the reaction mixture.The residue was then extracted with EtOAc (4 × 5 mL), and the combined extractswere dried over MgSO4. The filtrate was evaporated, and the esterwas obtained as the only product. |
86% | With alum doped nanopolyaniline at 100℃; for 8h; Green chemistry; | 2.3. General procedure for acylation of alcohols and amines General procedure: In a typical reaction procedure, substituted alcohols (1.5 mmol) oramines (1.5 mmol) with acetic acid (3 mmol) were taken in to 50 mLround bottom flask and 0.037 g (0.3 mol %) of NDPANI catalyst added tothe reaction mass. The reaction was maintained at 100 C with constantstirring. The progress of the reaction was monitored by TLC. Aftercompletion of the reaction, the catalyst was recovered from the reactionmixture by simple filtration and washed several times with ethyl acetate,then dried in the oven for reuse. To remove excess acetic acid, saturatedsolution of NaHCO3 was added to the reaction mixture. The product wasextracted with chloroform and the organic layer was dried by usinganhydrous Na2SO4 and evaporated under vacuum. In few cases thecrude product was then subjected to a short silica bed with hexane andethyl acetate (8:2) mixture to eluate the corresponding acetate/amideproducts in high purity. All the products were characterized by using 1HNMR and 13C NMR spectra. |
85% | With copper(II) nitrate for 8h; Heating; | |
80% | With ZrCl4-Mg(ClO4)2 composite In neat (no solvent) at 20℃; for 0.333333h; | Typical experimental procedure for the onepotsynthesis of benzyl acetate General procedure: A mixture of 4-methoxy benzyl alcohol (1b, 1 mmol),acetic acid (3 mmol), 2 mol% ZrCl4-Mg(ClO4)2 catalyst was stirred at room temperature for the time specified inTable 5. After completion of reaction (monitored by TLC),the solid or liquid product was filtered and washed with25 ml diethyl ether and water. The organic layer wassuccessively washed with saturated NaHCO3 solution. Theorganic layer was dried over anhydrous sodium sulfateand evaporated of the solvent under reduced pressure toprovide a residue which was passed through a short padof silica gel (60-120 mesh) using hexane as eluent to providethe analytically pure acylated product (please seeAppendix S1).Note that as we know that esterification is a reversiblereaction, to avoid this reversible we used every time activatedmolecular sieves as dehydrating agent/waterabsorbing agent. We have not mentioned it in our actualexperimental procedure. |
77% | With dmap; dicyclohexyl-carbodiimide In N,N-dimethyl-formamide at 0 - 25℃; | |
76% | With sulfonic acid-functionalized periodic mesoporous organosilicas with ethyl bridging group at 60℃; for 24h; | |
75% | With ethyl triphenylphosphonium tribromide for 0.416667h; Reflux; | |
With sodium tetrahydroborate 2) 85 deg C to 90 deg C, 3 h; Yield given. Multistep reaction; | ||
at 130℃; for 0.0166667h; microwave irradiation; | ||
98 %Chromat. | With silver nanoparticle embedded mesoporous polyaniline nanocomposite at 100℃; for 3h; | |
85 %Chromat. | With 4,4'‑trimethylene‑N,N‑dipiperidinium sulfate In cyclohexane at 75℃; for 4h; | Typical Esterification Procedure General procedure: Glacial acetic acid (0.600 g, 0.572 mL, 10 mmol), n-butanol (9.694 g, 11.968 mL, 13 mmol), [TMDPH2][SO4] (0.308 g,1.0 mmol), and cyclohexane (1.157 g, 15 mL) were taken into a 25mL three necked flask. The flask was equipped with a manifold and a condenser. After an appropriate reaction time (4 h), a liquid bi-phase formed in the flask. The liquid phase containing the ester was isolated by separating funnel and was analysed by GC-MS. [TMDPH2][SO4] was isolated after removing theproduct and water by separating funnel and drying in a vacuumoven at 508 C overnight before being tested for reusability. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With triethylamine In dichloromethane at 0℃; for 1h; Inert atmosphere; | 4-Nitrobenzyl methanesulfonate 23. To a flask containing a solution of 4-Nitrobenzyl alcohol (0.613 g, 4.00 mmol) in CH2C12 (16 mL) at 0 °C were added methanesulfonyl chloride (0.325 mL, 4.20 mmol) and Et3N (0.665 mL, 4.80 mmol). The reaction was stirred for 1 h at 0 °C, and water (20 mL) was added. The reaction mixture was extracted with CH2C12 (3 χ 20 mL), and the combined organic layer was washed with brine, dried over Na2S04, filtered, and concentrated under reduced pressure to afford desired mesylate 23 (0.829 g, 3.59 mmol, 90% yield) as a yellow solid. [000223] NMR (600 MHz, CDC13) 6 8.28 (2H, d, J= 8.8 Hz), 7.60 (2H, d, J = 8.8 Hz), 5.33 (2H, s), 3.07 (3H, s) [000224] l3C NMR (150 MHz, CDC13) δ 148.3, 140.7, 129.0, 124.1 , 69.1 , 38.3. |
88% | With triethylamine In tetrahydrofuran at 15℃; for 0.5h; Cooling with ice; | |
87% | at 0 - 5℃; for 60h; |
74% | With triethylamine In dichloromethane at 0 - 80℃; for 4h; | 5.1 Step 1: To a stirred solution of (4-nitrophenyl)methanol (299 mg, 1.952 mmol) in dichloromethane were added triethylamine (0.3 mL, 2.147 mmol). Methanesulfonyl chloride (0.18 mL, 2.343 mmol) is added dropwise at 0° C. The reaction mixture was heated to 80° C. and stirred for 4 h, then cooled to room temperature and diluted with dichloromethane. The mixture was washed with water. The organic layer was dried over magnesium sulfate and filtered. The filtrate removed in vacuo. The crude was purified by column chromatography. 4-Nitrobenzyl methanesulfonate (333 mg, 74%) was obtained. |
74% | With triethylamine In dichloromethane at 0 - 80℃; for 4h; | B28.1 Step 1 : To a stirred solution of 1 (299 mg, 1 .952 mmol) in dichloromethane was added triethylamine (0.3 ml, 2.147 mmol). Methanesulfonyl chloride (0.18 ml, 2.343 mmol) is added dropwise at Ο °C. The reaction mixture was heated to 80 °C and stirred for 4 hours, then cooled to room temperature, and diluted with dichloromethane. The mixture was washed with water. The organic layer was dried (MgSO4) and filtered. The solvent was removed in vacuo. The crude was purified by column chromatography. 2 (333 mg) was obtained in 74 % yield. |
72% | In toluene at 20 - 80℃; for 4h; | 2.1 Step 1 Step 1: To a solution of No.52 (4-nitrophenyl)methanol (2 g, 13.06 mmol) in No.53 toluene (10 mL) was slowly added No.47 methane sulfonylchloride (1.21 mL, 15.67 mmol) at room temperature. The reaction mixture was heated to 80° C. for 4 h. TLC showed complete consumption of starting material. The reaction mixture was cooled to room temperature. The mixture was extracted with ethyl acetate and washed with water and brine. The extract was dried over magnesium sulfate and concentrated under reduced pressure. The crude was purified by column chromatography to give No.54 4-nitrobenzyl methanesulfonate (2.2 g, 72%).Step 2: A solution of No.54 4-nitrobenzyl methanesulfonate (2.2 g, 9.51 mmol) in No.56 dimethylformamide (10 mL) was added No.57 potassium phthalimide (1.9 g, 10.5 mmol) and stirred at room temperature for overnight. TLC showed complete consumption of starting material. The mixture was extracted with ethyl acetate and washed with water and brine. The extract was dried over magnesium sulfate and concentrated under reduced pressure. The crude was purified by crystallization to give No.58 2-(4-nitrobenzyl)isoindoline-1,3-dione (1.6 g, 60%).Step 3: No.58 2-(4-Nitrobenzyl)isoindoline-1,3-dione (1.4 g, 4.96 mmol) was dissolved in No.27 tetrahydrofuran (8 mL). To the solution No.60 hydrazine monohydrate (1.48 mL, 19.84 mmol) and No.61 p-toluenesulfonic acid monohydrate (94 mg, 0.5 mmol) was added. It was refluxed for 6 h. TLC showed complete consumption of starting material. The mixture was extracted with ethyl acetate and washed with water and brine. The extract was dried over magnesium sulfate and concentrated under reduced pressure. The crude was purified by column chromatography to give No.62 (4-nitrophenyl)methanamine (651 mg, 86%).Step 4: No.62 (4-Nitrophenyl)methanamine (651 mg, 4.28 mmol) was dissolved in No.64 pyridine (4 mL).The reaction mixture was added No.65 methane sulfonyl chloride (0.43 mL, 5.56 mmol) and stirred for 1 h at room temperature. TLC showed complete consumption of starting material. The mixture was diluted with 1N HCl and extracted with ethyl acetate. The extract was dried over magnesium sulfate and concentrated under reduced pressure. The crude was purified by column chromatography to give No.66 N-(4-nitrobenzyl)methanesulfonamide (881 mg, 89%).Step 5: No.66 N-(4-Nitrobenzyl)methanesulfonamide (881 mg, 3.83 mmol) was dissolved in No.22 methanol/No.27 tetrahydrofuran (1:1, 35 mL). 10% No.68 Pd/C (264 mg, 3 eq) was added to it. The resulting mixture was stirred at room temperature for overnight under H2. TLC showed complete consumption of starting material. The mixture was filtered through celite bed and the filterate was concentrated under reduced pressure. The crude was purified by column chromatography to give No.69 N-(4-aminobenzyl)methanesulfonamide (352 mg, 46%).Step 6: No.69 N-(4-Aminobenzyl)methanesulfonamide (352 mg, 1.76 mmol) was dissolved in No.71 acetonitrile (3 mL) and No.27 tetrahydrofuran (4 mL). The reaction mixture was added No.64 pyridine (0.17 mL, 2.11 mmol) and No.72 phenyl chloroformate (0.23 mL, 1.85 mmol) and stirred at room temperature for 3 h under nitrogen atmosphere. TLC showed complete consumption of starting material. The reaction mixture was diluted with water and extracted with ethyl acetate. The organic part was washed with water and brine. The organic layer was dried over magnesium sulfate and concentrated under reduced pressure. The crude was purified by column chromatography to give No.73 phenyl 4-(methylsulfonamidomethyl)phenylcarbamate (438 mg, 78%).Step 7: To a solution of phenyl 4-(methylsulfonamidomethyl)phenylcarbamate (59 mg, 0.18 mmol) acetonitrile (3 mL) was added 4-dimethylaminopyridine (23 mg, 0.18 mmol) and (2-m-tolyl-6-(trifluoromethyl)pyridin-3-yl)methanamine (49 mg, 0.18 mmol) at room temperature. The reaction mixture was heated to 50° C. for 16 h. TLC showed complete consumption of starting material. The reaction mixture was diluted with water and extracted with ethyl acetate. The organic part was washed with water and brine. The organic layer was dried over magnesium sulfate and concentrated under reduced pressure. The crude was purified by column chromatography to N-(4-(3-((2-m-tolyl-6-(trifluoromethyl)pyridin-3-yl)methyl)ureido)benzyl)methanesulfonamide (example 2) (57 mg, 63%).1H NMR (300 MHz, CD3OD) δ 8.10 (d, 1H, J=7.50 Hz, Ar-H), 7.77 (d, 1H, J=8.07 Hz, Ar-H), 7.25-7.43 (m, 8H, Ar-H), 4.45 (s, 2H, Ar-CH2), 4.17 (s, 2H, Ar-CH3), 2.81 (s, 3H, Ms-CH3), 2.43 (s, 4H, Ar-CH3. |
72% | In toluene at 20 - 80℃; for 4h; | 82.1 Step 1 Step 1: To a solution of (4-nitrophenyl)methanol (2 g, 13.06 mmol) in toluene (10 mL) was slowly added methane sulfonylchloride (1.21 mL, 15.67 mmol) at room temperature. The reaction mixture was heated to 80° C. for 4 h. TLC showed complete consumption of starting material. The reaction mixture was cooled to room temperature. The mixture was extracted with ethyl acetate and washed with water and brine. The extract was dried over magnesium sulfate and concentrated under reduced pressure. The crude was purified by column chromatography to 4-nitrobenzyl methanesulfonate (2.2 g, 72%).[0509]Step 2: A solution of 4-nitrobenzyl methanesulfonate (2.2 g, 9.51 mmol) in dimethylformamide (10 mL) was added potassium phthalimide (1.9 g, 10.50 mmol) and stirred at room temperature for overnight. TLC showed complete consumption of starting material. The mixture was extracted with ethyl acetate and washed with water and brine. The extract was dried over magnesium sulfate and concentrated under reduced pressure. The crude was purified by crystallization to 2-(4-nitrobenzyl)isoindoline-1,3-dione (1.6 g, 60%).[0510]Step 3: No.58 2-(4-Nitrobenzyl)isoindoline-1,3-dione (1.6 g, 5.67 mmol) was dissolved in No.27 tetrahydrofuran (8 mL). To the solution No.60 hydrazine monohydrate (1.7 mL, 22.675 mmol) and No.61 p-toluenesulfonic acid monohydrate (108 mg, 0.57 mmol) was added. It was refluxed for 6 h. TLC showed complete consumption of starting material. The mixture was extracted with ethyl acetate and washed with water and brine. The extract was dried over magnesium sulfate and concentrated under reduced pressure. The crude was purified by column chromatography to give No.62 (4-nitrophenyl)methanamine (715 mg, 83%).[0511]Step 4: No.62 (4-Nitrophenyl)methanamine (715 mg, 4.7 mmol) was dissolved in No.64 pyridine (4 mL). The reaction mixture was added No.266 ethane sulfonyl chloride (0.58 mL, 6.11 mmol) and stirred for 1 h at room temperature. TLC showed complete consumption of starting material. The mixture was diluted with 1N HCl and extracted with ethyl acetate. The extract was dried over magnesium sulfate and concentrated under reduced pressure. The crude was purified by column chromatography to give No.267 N-(4-nitrobenzyl)ethanesulfonamide (776 mg, 68%).[0512]Step 5: No.267 N-(4-Nitrobenzyl)ethanesulfonamide (776 mg, 3.18 mmol) was dissolved in No.22 methanol and No.27 tetrahydrofuran (1:1, 35 mL). 10% No.68 Pd/C (264 mg, 3 equiv) was added to it. The resulting mixture was stirred at room temperature for overnight under H2. TLC showed complete consumption of starting material. The mixture was filtered through celite bed and the filterate was concentrated under reduced pressure. The crude was purified by column chromatography to give No.269 N-(4-aminobenzyl)ethanesulfonamide (504 mg, 74%).[0513]Step 6: No.269 N-(4-Aminobenzyl)ethanesulfonamide (504 mg, 2.35 mmol) was dissolved in No.71 acetonitrile (3 mL) and No.27 tetrahydrofuran (4 mL). The reaction mixture was added No.64 pyridine (0.23 mL, 2.78 mmol) and No.72 phenyl chloroformate (0.31 mL, 2.43 mmol) and stirred at room temperature for 3 h under nitrogen atmosphere. TLC showed complete consumption of starting material. The reaction mixture was diluted with water and extracted with ethyl acetate. The organic part was washed with water and brine. The organic layer was dried over magnesium sulfate and concentrated under reduced pressure. The crude was purified by column chromatography to give No.271 phenyl 4-(ethylsulfonamidomethyl)phenylcarbamate (697 mg, 87%).[0514]Step 7: To a solution of No.271 phenyl 4-(ethylsulfonamidomethyl)phenylcarbamate (74 mg, 0.22 mmol) in No.71 acetonitrile (3 mL) was added No.191 4-dimethylaminopyridine (27 mg, 0.22 mmol) and No.36 (2-m-tolyl-6-(trifluoromethyl)pyridin-3-yl)methanamine (59 mg, 0.22 mmol) at room temperature. The reaction mixture was heated to 50° C. for 15 h. TLC showed complete consumption of starting material. The reaction mixture was diluted with water and extracted with ethylacetate. The organic part was washed with water and brine. The organic layer was dried over magnesium sulfate and concentrated under reduced pressure. The crude was purified by column chromatography to give No.273 N-(4-(3-((2-m-tolyl-6-(trifluoromethyl)pyridin-3-yl)methyl)ureido)benzyl)ethanesulfonamide (example 82) (50 mg, 45%).[0515]1H NMR (300 MHz, CD3OD) δ 8.10 (d, 1H, J=8.07 Hz, Ar-H), 7.78 (d, 1H, J=8.22 Hz, Ar-H), 7.24-7.43 (m, 8H, Ar-H), 4.45 (s, 2H, Ar-CH2), 4.15 (s, 2H, CH3), 2.87-2.94 (q, 2H, J=7.32 Hz, CH2), 2.43 (s, 3H, Ar-CH3), 2.23 (t, 3H, J=7.32 Hz, CH3) |
72% | In toluene at 20 - 80℃; for 4h; | 2.1 Step 1 : To a solution of (4-nitrophenyl)methanol (2 g, 13.06 mmol) in toluene (10 ml_) was slowly added methane sulfonylchloride (1 .21 ml_, 15.67 mmol) at room temperature. The reaction mixture was heated to 80 °C for 4 h. TLC showed complete consumption of starting material. The reaction mixture was cooled to room temperature. The mixture was extracted with ethyl acetate and washed with water and brine. The extract was dried over magnesium sulfate and concentrated under reduced pressure. The crude was purified by column chromatography to give 4-nitrobenzyl methanesulfonate (2.2 g, 72 %). |
72% | In toluene at 20 - 80℃; for 4h; | 4.1 Step 1 : To a solution of (4-nitrophenyl)methanol (2 g, 13.06 mmol) in toluene (10 mL) was slowly added methane sulfonylchloride (1 .21 mL, 15.67 mmol) at room temperature. The reaction mixture was heated to 80 °C for 4 h. TLC showed complete consumption of starting material. The reaction mixture was cooled to room temperature. The mixture was extracted with ethyl acetate and washed with water and brine. The extract was dried over magnesium sulfate and concentrated under reduced pressure. The crude was purified by column chromatography to give 4-nitrobenzyl methanesulfonate (2.2 g, 72 %). |
With pyridine at -10℃; for 0.5h; | ||
With triethylamine In tetrahydrofuran at -10℃; for 0.5h; | ||
With triethylamine In toluene at 0℃; | ||
With triethylamine In dichloromethane at -50℃; | ||
With triethylamine In dichloromethane for 12h; Cooling with ice; | 5.1.5. Benzyl methanesulfonate (11a) General procedure: To a solution of compound 8a (1.08 g, 10 mmol) and Et3N (1.52g, 15 mmol) in anhydrous DCM (100 mL) was added dropwisemethanesulfonyl chloride (1.36 g, 12 mmol) in anhydrous DCM(20 mL). The mixture was stirred for 12 h while being cooled withan ice-water bath. DCM was evaporated under vacuum. The residuewas dissolved in EtOAc (100 mL) and washed with 10% HCl(3 100 mL), saturated NaHCO3 (3 100 mL) and brine (3 100mL), and then dried over MgSO4 overnight. EtOAc was evaporatedto give 11a as yellow oil (1.77 g, yield: 95%). ESI-MS m/z 187.4 [M+H]+. The crude product was used directly in the next reactionwithout further purification.Compounds 11b-11w, 11aa-11ff and 23a-23h were preparedusing the same procedure described above. | |
With triethylamine In dichloromethane at -50℃; Inert atmosphere; | Synthesis of benzyl methanesulfonate (2a) General procedure: Benzyl alcohol (1.08 g, 10.0 mmol) and anhydrousdichloromethane (DCM, 20 mL) were added to a 50 mLround-bottom flask under nitrogen atmosphere. The mixturewas cooled to -50 °C and then triethylamine (2.78 mL,20.0 mmol) was added, followed by slow addition ofmethanesulfonyl chloride (Ms-Cl, 1.20 mL, 15.0 mmol).The progress of the reaction was monitored by TLC. Afterits completion, 20 mL of water were added. The layerswere separated and the organic layer was washed with1% m/v HCl aqueous solution (3 × 15 mL), followed byNaHCO3 saturated aqueous solution (3 × 5 mL), dried overMgSO4, and concentrated under reduced pressure. Thecompound 2a was obtained in 87% yield (1.63 g, 8.76 mmol)and it was not submitted to any further purificationprocedure. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | Stage #1: benzoic acid With 2,2,4,4,6,6-hexachloro-1,3,5-triaza-2,4,6-triphosphorine In neat (no solvent) at 20℃; for 0.0166667h; Stage #2: 4-nitrobenzyl chloride In neat (no solvent) at 20℃; for 0.116667h; | Generalprocedure for the preparation of esters 3a-n General procedure: A mixture of carboxylic acid (1 mmol) and TAPC (0.5 mmol, 0.17 g) was prepared in a mortar. The mixturewas ground with a pestle for 1 min. Then alcohol (1 mmol) was added to thereaction mixture and grinding was continued at room temperature for appropriatereaction times indicated in Table 1. After completion of the reaction(monitored by TLC), H2O (10 mL) was added to the reaction mixture.The residue was then extracted with EtOAc (4 × 5 mL), and the combined extractswere dried over MgSO4. The filtrate was evaporated, and the esterwas obtained as the only product. |
84% | With graphene oxide In 1,2-dichloro-ethane at 100℃; for 24h; | General procedure for the synthesis of esters from acids and alcohols General procedure: A mixture of acid (0.2 mmol), alcohol (0.6 mmol) and GO (50 wt%, calculated with the mass of acid) in ethyl alcohol or DCE (1 mL) was placed in a test tube equipped with a magnetic stirring bar. The mixture was stirred at 100 °C for 24 h. After the reaction was finished, filtered the GO, solvent was removed, and the residue was separated by column chromatography to give the pure sample. |
82% | With TEA; diphenyl (2,3-dihydro-2-thioxo-3-benzoxazolyl)phosphonate In various solvent(s) for 2h; Ambient temperature; |
71% | With 1-methyl-pyrrolidin-2-one; 3,3'-(phenylphosphinylidene)bis<2(3H)-benzothiazolone; triethylamine for 3h; Ambient temperature; | |
70% | With TEA; 1,2-benzisoxazol-3-yl diphenyl phosphate In various solvent(s) for 3h; Ambient temperature; | |
42% | With dmap; dicyclohexyl-carbodiimide In N,N-dimethyl-formamide at 0 - 25℃; | |
33% | With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; for 3h; | To an ice cold solution of 4-nitrobenzyl alcohol (0.652mmol), benzoic acid (0.979mmol) and 4-dimethylaminopyridine (DMAP, 1.30mmol) in dry DCM (10mL), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC.HCl, 1.30mmol) was added. The reaction was stirred at room temperature for 3h.The reaction mixture was diluted with water (25mL) and the resulting aqueous mixture was extracted with DCM (3×10mL). The combined organic layer was washed with brine, dried over anhydrous Na2SO4, filtered and the filtrate was evaporated to give crude product. Silica gel chromatography (10% ethyl acetate: pet ether) of the resulting crude gave 5b (33%) as a white solid. Analytical data for 5b: 1H NMR (CDCl3, 400MHz) δ: 8.23 (d, J=8.7Hz, 2H), 8.07 (d, J=8.6Hz, 2H), 7.57-7.60 (m, 3H), 7.45 (t, J=7.4Hz, 2H), 5.44 (s, 2H); 13C NMR (CDCl3, 100MHz) δ: 166.0, 147.6, 143.3, 133.4, 129.7, 128.5, 128.3, 123.8, 65.1. See: Ohno, O.; Ye, M.; Koyama, T.; Yazawa, K.; Mura, E.; Matsumoto, H.; Ichino, T.; Yamada, K.; Nakamura, K.; Ohno, T.; Yamaguchi, K.; Ishida, J.; Fukamizu, A.; Uemura, D. Bioorg. Med. Chem.2008, 16, 7843. |
31% | With alumina sulfuric acid at 110℃; for 5h; | |
With pyridine; C15H12N2O3; triethylamine 1.) N-methyl-2-pyrrolidone (NMP), 50 deg C, 1 h, 2.) N-methyl-2-pyrrolidone (NMP), RT, 3 d; Yield given. Multistep reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With 1,8-diazabicyclo[5.4.0]undec-7-ene In dichloromethane at 20℃; for 7h; Inert atmosphere; | |
97% | With 1,8-diazabicyclo[5.4.0]undec-7-ene In dichloromethane at 0℃; Inert atmosphere; | |
96% | Stage #1: 4-nitrobenzyl chloride With 1,8-diazabicyclo[5.4.0]undec-7-ene In dichloromethane at 20℃; for 0.25h; Inert atmosphere; Stage #2: trichloroacetonitrile In dichloromethane at 0 - 20℃; for 18h; Inert atmosphere; | General procedure A (for the synthesis of trichloroacetimidates from the alcohol) General procedure: DBU (0.1 equiv) was added to a solution of the alcohol (1.0 equiv) in 0.3M anhydrous DCMunder argon. The mixture was stirred at room temperature for 15 min and then cooled to 0 °C.Trichloroacetonitrile (1.2 equiv) was then added, and the reaction mixture was allowed to warmto room temperature and stirred for 18 h. The reaction mixture was then concentrated and theresidue purified by silica gel chromatography (using the listed solvent system) to give thetrichloroacetimidate. |
95% | With sodium hydride In tetrahydrofuran | |
92% | With 1,8-diazabicyclo[5.4.0]undec-7-ene In dichloromethane at 20℃; for 3.5h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97% | With sulfur monochloride; triethylamine In dichloromethane at 0℃; for 3h; | |
93% | With disulfur dichloride; triethylamine In dichloromethane at 0 - 20℃; for 5.33333h; Inert atmosphere; | Bis(4-nitrobenzyloxy) disulfide (1) General procedure: p-Nitrobenzyl alcohol (0.25 g, 1.63 mmol) was dissolved in anhydrous CH2Cl2 under N2. Triethylamine (0.227 mL, 1.63 mmol) was added and the resulting solution was cooled to 0 °C. S2Cl2 (65.3 μL, 0.82 mmol) was added dropwise over 20 min. The solution was stirred at 0 °C for 2 h before being allowed to equilibrate to room temperature for 3 h. The reaction was quenched with dH20, washed with 2 × 20 mL aliquots of brine. The aqueous phase was extracted with CH2Cl2 (2 × 10 mL), and the combined organic was dried over MgSO4, filtered, and concentrated under reduced pressure. Column chromatography with a 2.5:1 ratio of hexanes:ethyl acetate afforded: |
93% | With disulfur dichloride; triethylamine In dichloromethane at 0 - 20℃; for 5.33333h; Inert atmosphere; | Bis(4-Nitrobenzyloxy) disulfide p-Nitrobenzyl alcohol (0.25 g, 1.63 mmol) was dissolved in anhydrous CH2Cl2 under N2. Triethylamine (0.227 mL, 1.63 mmol) was added and the resulting solution was cooled to 0 °C. S2Cl2 (65.3 μL, 0.82 mmol) was added dropwise over twenty minutes. The solution was stirred at 0 °C for two hours before being allowed to equilibrate to room temperature for three hours. The reaction was quenched with dH2O, washed with 2 x 20 mL aliquots of brine. The aqueous phase was extracted with CH2Cl2 (2 x 10 mL), and the combined organic phase was dried over MgSO4, filtered, and concentrated under reduced pressure. Column chromatography with a 2.5:1 ratio of hexanes:ethyl acetate afforded the below compounds. [Note: Bis(p-nitrobenzyloxy) disulfide, bis(4-methoxybenzyloxy) disulfide, bis(4-tertbutylbenzyloxy) disulfide, and bis(4-benzyloxy) disulfide have been previously synthesized in another laboratory with reported spectra in Ref. [13]. With the exception of bis(4-benzyloxy) disulfide, all spectra reported was almost identical to those reported below. For bis(4-benzyloxy) disulfide, Ref. [13] incorrectly assigned the aromatic signals as d 7.39 (m, 15H) instead of our d 7.17 (m, 10H). In addition, bis(p-nitrobenzyloxy) disulfide, bis(4-methoxybenzyloxy) disulfide, bis(4-methylbenzyloxy) disulfide, bis(4-benzyloxy) disulfide, and bis(4-chlorobenzyloxy) disulfide were also reported in Ref. [4]. The mp. and NMR matched our samples. Bis(4-phenylbenzyloxy) disulfide was first synthesized and fully characterized in our laboratory in Ref. [16]. Bis(4-phenoxybenzyloxy) disulfide, bis(4-cyanobenzyloxy) disulfide, and bis(4-cyanobenzyloxy) disulfide all were previously synthesized and fully characterized from our laboratory and reportedin Ref. [18]. |
90% | With disulfur dichloride; triethylamine | |
90% | With disulfur dichloride In triethylamine | |
With disulfur dichloride; triethylamine In dichloromethane at 0℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With bismuth(lll) trifluoromethanesulfonate In methanol at 20℃; for 0.0666667h; | |
99% | With methanol; 1,3-disulfonic acid imidazolium hydrogen sulfate at 20℃; for 0.116667h; Green chemistry; | General procedure for the deprotection of trimethylsilyl ethers General procedure: A mixture of the substrate (1 mmol), ionic liquid [Dsim]HSO4 (6.5 mg, ∼0.02 mmol) in methanol (2 mL) was stirred at room temperature. After completion of the reaction (monitored by TLC), solvent was evaporated, water (1 mL) was added to the mixture, and stirred vigorously. Decantation of the mixture gave almost pure product(s). The products were characterized by comparison of their IR and NMR data. The ionic liquid was dried at 65 ◦C under vacuum to remove moisture, and then reused. |
97% | With Oxone In methanol for 0.25h; Heating; |
96% | With water; boric acid at 20℃; for 1h; | |
96% | With poly (ethylene glycol)-sulfonated sodium montmorillonite nanocomposite In methanol at 20℃; for 0.0333333h; | General procedure for deprotection of silyl ethers General procedure: A mixture of the substrate (1 mmol) and the PEG-SANMnanocomposite (8 mg) in methanol (2 mL) was stirred at roomtemperature. After completion of the reaction (monitored byTLC), the catalyst was filtered off and the solvent was evaporatedunder reduced pressure. The crude product was purifiedby column chromatography on silica gel to yield pure alcoholsand phenols. |
96% | With 1,4-diazabicyclo[2.2.2]octane tribromide supported on magnetic Fe3O4 nanoparticles In methanol at 20℃; for 0.0833333h; | |
95% | With silica triflate In methanol for 0.0666667h; Heating; | |
95% | With benzyltriphenylphosphonium tribromide In methanol at 20℃; for 0.05h; | |
94% | With rice husk ash supported on anatase-phase titania nanoparticles nanocomposite In methanol at 20℃; for 0.0833333h; | |
94% | With Nanoporous Na+-Montmorillonite Perchloric Acid In ethanol at 20℃; for 0.0333333h; | 2.5. General Procedure for Deprotection ofTrimethylsilyl Ethers General procedure: A mixture of the substrate (1 mmol) and MMT-HClO4(10 mg) in ethanol (2 mL) was stirred at room temperature.The progress of the reaction was monitored by TLC, ethylacetate: n-hexane (3:7). After completion of the reactionthe catalyst was filtered off and the solvent was evaporatedunder reduced pressure. The crude product was purifiedby column chromatography on silica gel (EtOAc:hexane=1:4) to gave the pure alcohol and/or phenol derivative ingood to high yields. |
90% | With 1-benzyl-1-azonia-4-azabicyclo[2.2.2]octane tetrahydroborate In <i>tert</i>-butyl alcohol for 1.25h; Heating; | |
90% | With Nafion-H(R); silica gel In hexane at 20℃; for 0.5h; | |
90% | With 1-butyl-3-methylimidazolium chloride at 20℃; for 2h; | |
90% | With aminosulfonic acid; water at 20℃; for 1.5h; | |
90% | With silicaphosphite (silphos), [PCl3-n(SiO2)n] In acetonitrile at 20℃; for 0.0333333h; | |
89% | With tris[trinitratocerium(IV)] paraperiodate at 20℃; for 0.0166667h; | |
85% | With trinitratocerium(IV) bromate at 20℃; for 0.0833333h; | |
85% | With methanol at 20℃; for 0.05h; | 2.5. General procedure for deprotection of trimethylsilyl ethers General procedure: A mixture of the substrate (1 mmol) and TiO2-HClO4 (5 mg) in methanol (1 mL) was stirred at room temperature. After completion of the reaction (indicated by TLC), the catalyst was filtered off and the solvent was evaporated under reduced pressure. The crude product was purified by column chromatography on silica gel to afford pure alcohols and phenols (Table 2). |
85% | With nano magnetic sulfated zirconia (Fe3O4 at ZrO2/SO42-) In neat (no solvent) at 20℃; for 0.333333h; Green chemistry; | General procedure for the deprotection of trimethylsilylethers (removal of TMS groups) using Fe3O4 at ZrO2/SO42- General procedure: To a mixture of trimethylsilyl ether (1.0 mmol), 80.0 mgFe3O4ZrO2/SO42-was added and the mixture was stirredat room temperature for an appropriate time (Table 3). Aftercompletion of the reaction, as indicated by thin-layer chromatography (TLC), 10.0 mL CCl4 was added to the reactionmixture, the catalyst was separated by an external magnet,and the product was obtained by evaporation of the volatileportion under reduced pressure. All compounds are known and were characterized on the basis of their spectroscopic data(IR,1H NMR) and by comparison with those reported in theliterature. |
100 % Chromat. | With K5<CoW12O40> In acetonitrile at 20℃; for 0.25h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With silica-supported NaHSO4 In methanol at 20℃; for 0.166667h; | |
96% | With bismuth(lll) trifluoromethanesulfonate In methanol for 0.0833333h; Heating; | |
95% | With silica triflate In methanol for 0.133333h; Heating; |
94% | With Oxone In methanol for 1h; Heating; | |
94% | With sulfuric acid; silica gel In methanol at 20℃; for 0.5h; | |
92% | With trichloroisocyanuric acid In methanol at 20℃; for 6h; | |
91% | In methanol for 0.0666667h; microwave irradiation; | |
91% | With iron(III) p-toluenesulfonate hexahydrate In methanol at 20℃; for 2.41667h; | Representative procedures General procedure: Method A: A solution of the THP ether of cinnamyl alcohol (entry 5) (1.00 g, 4.58 mmol) in CH3OH (10 mL) was stirred at room temperature as Fe(OTs)3·6H2O (0.0621 g, 0.0916 mmol, 2.0 mol %) was added. The reaction progress was monitored by TLC (EtOAc/heptane, 30/70). After 4 h 30 min, water (15 mL) was added and methanol was removed on a rotary evaporator. The resulting mixture was extracted with EtOAc (2 × 20 mL). The organic layer was washed with saturated aqueous NaHCO3 (15 mL), saturated aqueous NaCl (15 mL), dried (Na2SO4), and concentrated on a rotary evaporator to yield 0.59 g of the crude product. The crude product was purified by flash chromatography (35 g silica gel, EtOAc/heptane, 30/70) to yield 0.49 g (80%) of a white solid that was identified to be cinnamyl alcohol. The purity was estimated to be >98% by 1H and 13C NMR spectroscopy, and GC analysis. Method B: A solution of the THP ether of 1-ethynyl-1-cyclohexanol (entry 10) (0.50 g, 2.40 mmol) in CH3OH (5 mL) was stirred at room temperature as Fe(OTs)3·6H2O (0.0325 g, 0.0480 mmol, 2.0 mol %) was added. The reaction progress was monitored by TLC (EtOAc/heptane, 30/70). After 2 h, CH3OH was removed on a rotary evaporator and the residue was purified by flash chromatography (35 g silica gel, EtOAc/pentane, 30/70) to yield 0.23 g (77%) of a colorless liquid that was identified to be 1-ethynyl-1-cyclohexanol. The purity was estimated to be >98% by 1H and 13C NMR spectroscopy, and GC analysis. |
90% | With silicaphosphite (silphos), [PCl3-n(SiO2)n] In acetonitrile for 1.5h; Reflux; | |
90% | With zinc(II) trifluoromethanesulfonate In methanol at 20℃; for 0.583333h; | |
90% | With methanol at 20℃; for 2.66667h; | General procedure for the deprotection of THP-ethers into correspondingalcohols or phenols General procedure: A mixture of THP-ethers (1 mmol) and MNPs-PSA (20 mg, 3.8 mol%) was stirred at room temperature in CH3OH (2 mL), and the progress of the reaction was monitored by TLC. After completion of the reaction, catalyst was separated by an external magnet and washed with CH2Cl2. Then, the solvent was removed under reduced pressure, and the product was purified through a short column of silica gel to obtain the pure alcohol or phenol. |
89% | With carbon tetrabromide In methanol at 65℃; for 1h; Heating; | |
89% | With bismuth(lll) trifluoromethanesulfonate In methanol; N,N-dimethyl-formamide at 110℃; for 6h; | |
88% | With sulfuric acid In methanol for 0.166667h; Heating; | |
87% | In water; acetonitrile for 11h; Heating; | |
80% | In water; acetonitrile at 20℃; for 4h; | |
79% | With lithium borohydride In methanol at 20℃; for 5.5h; | |
76% | With 1,4-diazabicyclo[2.2.2]octane tribromide supported on magnetic Fe3O4 nanoparticles In methanol at 20℃; | |
75% | With cerium(III) chloride In methanol at 20℃; for 4h; | |
98 % Chromat. | With H14[NaP5W30O110] In methanol for 2h; Heating; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With 1H-imidazole In N,N-dimethyl-formamide at 20℃; for 2.5h; | |
100% | With 1H-imidazole In N,N-dimethyl-formamide at 20℃; for 1.5h; | |
99% | With triethylamine In tetrahydrofuran at 20℃; for 95h; | 2.1; 3.1 Step 1: Preparation of tert-butyldimethyl((4-nitrobenzyl)oxy)silane 4-nitrobenzyl alcohol (300 mg, 1.96 mmol) was dissolved in tetrahydrofuran (THF, 4 ml),Stir at room temperature.TEA (0.82 ml, 5.88 mmol) and tert-butyldimethylsilyl chloride (TBDMSCl, 1 M in THF solution, 4.8 ml, 4.80 mmol) were added to the reaction solution, followed by stirring at the same temperature for 95 hours.next,Add EA to the reaction solution and dilute it.Washed several times with distilled water,The extracted organic layer was dried with MgSO 4 and filtered under reduced pressure.The filtrate was concentrated under reduced pressure and purified by silica gel column chromatography to obtain the title compound.520 mg of colorless oil (99% yield); |
98% | With 1H-imidazole In N,N-dimethyl-formamide at 20℃; for 2h; | |
98% | With 1H-imidazole In N,N-dimethyl-formamide at 0 - 20℃; for 3h; | |
98% | With 1H-imidazole In dichloromethane at 20℃; | General Procedure General procedure: To a round bottom flask equipped with a stir bar was added the alcohol substrate (1.0 equiv.),TBS-Cl (1.05 equiv.) and DCM (0.164 M in the alcohol). Imidazole (1.1 equiv.) was added andthe solution was allowed to stir at room temperature overnight. The reaction was then quenchedwith pentane (0.819 M in the alcohol). After quenching, the crude mixture was poured atop amedium filter funnel filled with approximately 1 inch of silica gel previously wet with hexanes.The product was then eluted with approximately 300 mL of a 95:5 by volume hexane to ethylacetate mixture. The eluent was dried with Na2SO4 and the solvent was removed in vacuo byrotary evaporation to give the pure product |
95% | With 1H-imidazole In DMF (N,N-dimethyl-formamide) at 20℃; for 72h; | i Synthesis of protecting group precursors: (i) 2- [3- (4-HYDROXYMETHYL-PHENYL) ureido] -pentanedioic acid diallyl ester (35) TERT-BUTYL-DIMETHYL- (4-NITRO-BENZYLOXY)-SILANE (32); A solution of t-butyldimethylsilyl chloride (8.53 g, 56.3 mmol, 1.3 EQ), imidazole (7.38 g, 108.3 mmol, 2.5 eq) and 4-nitro- benzyl alcohol (6.64 g, 43.3 mmol, 1 eq) in anhydrous DMF (25 mL) was stirred at room temperature under a N atmosphere for 72 h. The reaction mixture was diluted with H2O (500 mL) and extracted with Etoac (4 x 100 mL). The combined organic extracts were washed with H2O (100 ML), satd NACLFAQ, (100 ML), dried (MGSO4) and evaporated in vacuo. The residue was triturated with n-hexane and filtered. The filtrate was evaporated in vacuo to give the product as a yellow oil which crystallised (11.02 g, 95%). 1H NMR (CDC13) 5 8.2 (d, J = 8.25 Hz, 2H), 7. 47 (d, J = 8. 02 Hz, 2H), 4.8 (s, 2H), 0.96 (s, 9H), 0.12 (s, 6H). IR (neat) 2955,2930, 1605 and 1522 cm-1. HRMS M/Z calcd for C13H22NO3 SI 268.1369 (M + H), found 268.1376 |
95% | With ferric hydrogen sulphate; triethylamine at 20℃; for 3h; Inert atmosphere; chemoselective reaction; | |
95% | With 1H-imidazole In N,N-dimethyl-formamide at 20℃; for 3h; | |
93% | With 1H-imidazole at 20℃; | |
90% | With triethylamine at 20℃; for 0.0833333h; Inert atmosphere; | |
90% | With 1H-imidazole In N,N-dimethyl-formamide at 20℃; for 4h; | 1.2 2) Synthesis of compound 3: Combine TBSCl (4.2 g, 28 mmol), 4-nitrobenzyl alcohol (3.06 g, 20 mmol) andImidazole (2.72 g, 40 mmol) was dissolved in anhydrous DMF solution (25 mL),After stirring for 4 hours at room temperature, the mixture was diluted with ethyl acetate (100 mL),Wash with water (3×100mL), dry with anhydrous Na2SO4, evaporate under reduced pressure to remove solvent,Column purification (petroleum ether/ethyl acetate=15/1) gave compound 3 with a yield of 90%. |
86% | With 1H-imidazole In dichloromethane at 20℃; for 18h; | |
79% | With 1H-imidazole In dichloromethane at 0 - 20℃; for 1.08333h; Inert atmosphere; | 15.1 Procedure 1: ((5-bromo-1,3-phenylene)bis(oxy))bis(tert-butyldimethylsilane) (2) To a stirring solution of compound (1) (1.00 g, 5.29 mmol) and imidazole (1.08 g, 15.9 mmol) in CH2CI2(25 mL) at rt under Ar was added tert-butyldimethylsilyl chloride (TBDMS-C1) (2.39 g, 15.9 mmol) in one lot. The resulting mixture was stirred at this temperature overnight. The reaction mixture was filtered to remove precipitated imidazole hydrochloride, and the filtrate was concentrated in vacuo to give a pale yellow oil. The crude material was purified over silica gel, eluting with hexane to afford compound (2) (1.75 g, 79%) as a colorless oil.1H NMR (300 MHz, CDCI3) δ ppm: 6.65 (d, J = 2.2 Hz, 2H), 6.27 (t, J= 2.1 Hz, 1H), 0.99 (s, 18H), 0.22 (s, 12H). |
With 1H-imidazole In N,N-dimethyl-formamide at 20℃; | ||
In N,N-dimethyl-formamide | 15 prepared from the corresponding p-nitrobenzyl alcohol and TBDMSC1 in DMF; followed by reduction using Zn/NH4C1 | |
With 1H-imidazole In N,N-dimethyl-formamide at 20℃; | ||
4.22 g | With 1H-imidazole In N,N-dimethyl-formamide at 0 - 20℃; | 21.1 Step 1: synthesis of tert-butyldimethyl((4-nitrobenzyl)oxy)silane (LB35-A) p-Nitrobenzyl alcohol (2.52 g, 16.46 mmol), imidazole (1.41 g, 20.58 mmol) and DMF (15 mL) were added to a 100 mL single necked flask, cooled to 0 °C, added dropwise with TBSCl (2.98 g, 19.75 mmol) and warmed to room temperature, and the reaction was monitored by LC-MS. The system was added with water (80 mL) and EA (20 mL), shaken and sepatated. The aqueous phase was extracted with EA (20 mL 2). The combined organic phase was washed with water (20 mL 3) and brine (40 mL), dried over anhydrous NaSO4 and filtered with suction. The filtrate was concentrated to obtain 4.22 g of the target compound, which was not further purified. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
83% | In acetonitrile; at 80℃;Inert atmosphere; | To a flame dried 150 mL pressure tube under argon was added Meldrum?s acid (5.00 g, 34.7 mmol) and anhydrous MeCN (40 mL). To the resulting solution was added p-nitrobenzyl alcohol (5.58 g, 36.4 mmol), the tube was tightly capped, and refluxed overnight. The reaction was concentrated under reduced pressure and purified with column chromatography (55/45 hexanes/EtOAc) to give 16a (6.86 g, 27.1 mmol) as an off-white solid in 83% yield. A small crop of this material (1.00 g) was recrystallized from t-butanol/hexanes to give 16a (225 mg, 0.889 mmol) as a white solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86% | With collidine In dichloromethane at 0 - 20℃; for 24h; | 5.g The synthesis of [Step g] 4-nitrobenzyl 2-bromoacetate(Compound 26) 4nitrobenzylalcohol (3.06 g, 20 mmol) andcollidine (2.9 mL, 22 mmol) was dissolved in dichloromethane (100mL), 0 ° C under was added bromoacetyl bromide (1.81mL, 20 mmol), and reacted for 24 hours at room temperature. The solvent was evaporated under reduced pressure, diethylether was added to the residue was removed by filtration of the precipitated crystals. After concentrating the filtrate, theresidue was purified by silica gel column chromatography (hexane / ethyl acetate) to give compound 26 (4.73 g, 86% yield). |
With pyridine In dichloromethane at 0℃; | ||
In diethyl ether; di-isopropyl ether; <i>N</i>,<i>N</i>-dimethyl-aniline | 93.1 Preparation 93 (1) To a mixture of p-nitrobenzyl alcohol (45 g) and N,N-dimethylaniline (37.2 ml) in a mixture of diisopropyl ether and diethyl ether (300 ml) was added dropwise bromoacetyl bromide (25 ml) at 30° to 35° C., and the reaction mixture was stirred at the same temperature for an hour. After the reaction mixture was poured into ice-water, the separated organic layer was washed with 5% aqueous sodium bicarbonate. The solution was evaporated under reduced pressure to give p-nitrobenzyl bromoacetate. |
With dmap; triethylamine In dichloromethane at 0 - 20℃; for 3h; | ||
With sodium hydrogencarbonate In acetonitrile at 0 - 4℃; for 0.75h; | General procedure for synthesis of benzyl 2-bromoacetates/1,4-phenylenebis(methylene) bis(2-bromoacetate) (2a-2e)/(5) General procedure: For synthesis of benzyl 2-bromooacetates/1,4-phenylene bis(methylene) bis(2-bromoacetate) (2a-2e)/(5), 1,4-phenylenedimethanol/benzyl alcohols (1.0 mmol) were taken in acetonitrile in round bottom flask. To this, sodium bicarbonate (1.5 mmol/3.0 mmol) was added as base followed by slow addition of bromoacetylbromide (1.2 mmol/2.4 mmol). The mixture was stirred with aid of magnetic stirrer at 0-4 °C for 45 min. Upon completion of reaction, product extracted with dichloromethane (3 × 30 mL) and evaporation of solvent in vacuum furnished product in good yield. | |
With sodium hydrogencarbonate In acetonitrile at 0 - 4℃; for 0.75h; | General procedure for synthesis of thioether-ester linked1-4 disubstituted 1,2,3-triazoles (5a-5y) General procedure: Thioether linked terminal alkynes i.e., aryl(prop-2-yn-1-yl)sulfanes (Kaushik et al. 2017) (2a-2e) were synthesized byreaction of aromatic thiols (1a-1e) (1.0 mmol) and propargylbromide (1.0 mmol) with potassium carbonate (3.0mmol) as base using N,N-dimethylformamide as solvent at10-25 °C temperature with constant stirring for 5-6 h.Reaction was monitored by TLC. Upon completion ofreaction, dilute hydrochloric acid was added to reactionmixture and compound was extracted with ethyl acetate(3 × 30 mL). Organic layer was removed by evaporationunder reduced pressure to get desired terminal alkynes(2a-2e).Synthesis of benzyl 2-bromoacetates (4a-4e) were carriedout by dropwise addition of bromoacetyl bromide (1.2mmol) in the stirred solution of benzyl alcohols (3a-3e)(1.0 mmol) in acetonitrile in the presence of sodium bicarbonate(1.5 mmol) as base at 0-4 °C and continued stirringfor 45 min. When the reaction was completed, reactionmixture was extracted with dichloromethane (3 × 30 mL).Organic layer was evaporated under vaccum to obtainproducts (4a-4e) in good yield.For the synthesis of triazole derivatives (5a-5y), benzyl2-bromoacetates (1.0 mmol) (4a-4e) were dissolved in N,Ndimethylformamidein round bottom flask and aqueoussodium azide (3.0 mmol) was added at 25-40 °C understirring which was continued for 1 h. Afterwards, aryl(prop-2-yn-1-yl)sulfanes (2a-2e) were added followed by aqueouscopper sulfate pentahydrate (0.1 mmol) and sodiumascorbate (0.4 mmol), to above reaction mixture which wasallowed to stirred for 8-18 h at same temperature. After thecompletion of reaction, ice cold water was added to thereaction contents and products were extracted with ethylacetate (3 × 30 mL), followed by washing with aqueousammonia solution and then with saturated brine solution.Thereafter, organic layer was dried over anhydrous sodiumsulfate, filtered and concentrated under reduced pressure toobtain crude solid which was further recrystallized fromchloroform to furnish pure compounds (5a-5y) in goodyields. | |
With sodium hydrogencarbonate In acetonitrile at 0℃; for 0.166667h; | ||
With sodium hydrogencarbonate In acetonitrile at 0 - 4℃; for 0.75h; | ||
With sodium hydrogencarbonate In acetonitrile at 0℃; for 0.5h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | Stage #1: 4-nitrobenzyl chloride With 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; iodine In dichloromethane at 20℃; for 2h; Inert atmosphere; Stage #2: With ammonia; iodine In dichloromethane; water at 20℃; for 2h; Inert atmosphere; | |
99% | Stage #1: 4-nitrobenzyl chloride With 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; iodine In dichloromethane at 20℃; for 2h; Stage #2: With ammonium hydroxide In dichloromethane at 20℃; for 2h; | 16 General procedure: With respect to 2 mmol of each alcohol represented by the general formula (1), 4 ml of CH 2 Cl 2 as a solvent, 0.05 equivalent of TEMPO as an N-nitrosyl compound, (A) t-BuOCl, (B) I 2 or (C ) N, N'-diiodo-5,5-dimethylhydantoin (DIH) were mixed in a predetermined amount and stirred for a predetermined time at room temperature.Next, 1.5 equivalents of I 2 and 4 ml of aqueous ammonia were added, and the mixture was stirred at room temperature for 2 hours. |
99% | With ammonium hydroxide; oxygen In tert-Amyl alcohol for 16h; Green chemistry; | 10 4- nitrobenzyl alcohol converted to 4-nitrobenzonitrile Sequentially capturing meso-Co-N / C (800) (35mg, 0.5mol% Co), 4- nitrobenzyl alcohol (77mg, 0.5mmol), a concentration of 28 mass% aqueous ammonia (280 L) was added to the reaction flask of 10ml, 1ml was then added as solvent tert-amyl alcohol, placed in a reaction vessel, the oxygen charged to 0.5Mpa, placed in an oil bath of 130 and then detecting the extent of reaction by GC-MS.After completion of the reaction, the biphenyl internal standard was added, the yield of product was analyzed quantitatively by GC.The reaction 16h, 4- nitrobenzonitrile in 99% yield, selectivity of greater than 99%. |
97% | With ammonium hydroxide; oxygen at 90℃; for 5h; | |
96% | With 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; [hydroxy(tosyloxy)iodo]benzene; ammonium acetate In water; acetonitrile at 80℃; for 3h; | |
95% | With ammonium acetate; iodine at 100℃; for 2h; | |
95% | With ammonia; oxygen In tert-Amyl alcohol; water at 130℃; for 24h; | |
92% | With 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; ammonia; oxygen; copper(II) nitrate In water; dimethyl sulfoxide at 80℃; for 5h; | |
92% | With Iron(III) nitrate nonahydrate; ammonium hydroxide; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical In acetonitrile at 20℃; for 12h; | |
92% | With ammonium hydroxide; copper(l) iodide; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; N-Phenylglycine In methanol at 50℃; for 24h; Cooling with ice; | 8 General procedure: Reactants used were p-methylbenzyl alcohol (122.03g, 1000mmol, i.e., of formula (I) wherein R is methyl, n = 1, m = 0 , X = C),cuprous iodide (9.50 g of , 50mmol), N- phenylglycine (7.51g, 50mmol), TEMPO ( 7.80g, 50mmol),sodium hydroxide (4.00g, 100mmol), aqueous ammonia (300mL, 25 ~ 28%) ,ethanol, 800mL, in an ice bath under the condition, with oxygen round bottom flask is evacuated of air ventilation 3 times, and then the system was stirred at 25 , 24h, after completion of the reaction, the reaction solution was cooled to room temperature, rotary evaporated to remove the solvent, the residue was washed with water filtered and dried The product was 107.64g, yield 92%. The reaction was used for the methanol nitrobenzene (30.60g, 200mmol, i.e., of formula (I) wherein R is nitro, X = C, n = 1 , m = 0), the experimental methods and procedures described in Example 2, except that: copper iodide (11.41g, 60mmol), N- phenylglycine (9.00g, 60mmol), TEMPO ( 1.56g, 10mmol), aqueous ammonia (60mL, 25 ~ 28%) , 160mL methanol , at 50 stirred at 24h, to give the final product was 28.15 g, yield 92%. |
92% | With 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; copper(II) nitrate; ammonium hydroxide at 100℃; for 24h; | 8 Example 8: The reaction used was 1.0 mmol (153.1 mg) of p-nitrobenzyl alcohol (i.e., R1 in position of formula (I))The experimental procedure and procedure were the same as in Example 1, aqueous ammonia (1.6 mol / L) 5.0 mL, catalyst copper nitrate was used in an amount of 5 mol%(9.38 mg), TEMPO was used in an amount of 8 mol% (12.5 mg) at a reaction temperature of 100 ° C and a reaction time of 24 h.Chromatography (petroleum ether: ethyl acetate = 5: 1) gave the pure title product, yielding 136.3 mg yield 92%. |
92% | With ammonium hydroxide; copper(l) iodide; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical In water for 24h; Reflux; Green chemistry; | |
90% | With 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; [bis(acetoxy)iodo]benzene; ammonium acetate In water; acetonitrile at 20℃; for 10h; | Oxidative Conversion of Alcohols into Nitriles; GeneralProcedure: General procedure: To a solution of alcohol (1 mmol) in MeCN-H2O (9:1, 3 mL) were successively added TEMPO (7.8 mg,5 mol%), NH4OAc (0.308 g, 4 equiv), and PhI(OAc)2 (0.708g, 2.2 equiv). The suspension was stirred at roomtemperature (progress of the reaction was monitored byTLC) for the reaction time indicated in Table 2. The resultantclear two-phase reaction mixture was concentrated, dilutedwith H2O and Et2O, and the organic layer was dried (Na2SO4), filtered, and evaporated under reduced pressure.The residue was purified by flash column chromatography(PE-Et2O or PE-CH2Cl2) to give 2. |
90% | With 1,4-diaza-bicyclo[2.2.2]octane; TEMPOL; ammonia; copper(l) chloride In water; acetonitrile at 20℃; for 24h; | General procedure for the synthesis nitriles in Table 2 General procedure: To a 25-mL Schlenk tube equipped with a magnetic stirrer, CuCl (0.05 mol, 5 mol%), DABCO (0.10 mol, 10 mol%), 4-HO-TEMPO (0.05 mmol, 5 mol%) were added. Substrates 1 (1 mmol) and NH3 (aq, 25-28%, 3 mmol, 3.0 equiv) in CH3CN (2 mL) were added subsequently. Then the reaction mixture was stirred at room temperature for 24 h in the presence of an air balloon. The progress of the reaction was monitored by TLC. After completion, the reaction mixture was diluted with water and extracted with ethyl acetate. The organic layer was dried over anhydrous MgSO4. Subsequently, the combined organic layer was concentrated under reduced pressure and the crude product was purified by column chromatography to afford the corresponding products |
90% | With ammonia; oxygen In 1,4-dioxane for 2.5h; Reflux; | |
90% | With ammonia; oxygen In ethanol; water for 2.5h; Reflux; | |
89% | With potassium hydroxide; ammonium bicarbonate; (Bu4N)2S2O8 In isopropyl alcohol at 25℃; for 1.5h; | |
89% | With ammonium hydroxide; 1,3-Diiodo-5,5-dimethyl-2,4-imidazolidinedione at 60℃; for 12h; | |
89% | With ammonium hydroxide; 1,3-Diiodo-5,5-dimethyl-2,4-imidazolidinedione at 60℃; for 12h; | |
88% | With ammonium hydroxide; oxygen In tert-Amyl alcohol at 130℃; for 24h; | |
86% | With ammonium hydroxide; trans-3,5-dihydroperoxy-3,5-dimethyl-1,2-dioxolane; ammonium bromide at 20℃; for 1.33333h; Green chemistry; | |
84% | With ammonium hydroxide; sodium periodate; potassium iodide at 60℃; for 3h; | |
81% | With manganese(IV) oxide; ammonia; magnesium sulfate In tetrahydrofuran; isopropyl alcohol at 20℃; for 18h; | |
81% | With ammonium hydroxide; dihydrogen peroxide In water; acetonitrile at 30℃; for 4h; | General procedure for the catalytic oxidation General procedure: In a typical experiment, alcohol (10 mmol), aqueous NH3*H2O (30 mmol), FeCl4-IL-SiO2 (0.5 g), and CH3CN (10 mL) were added to a round-bottomed flask. Then, aqueous 30 % H2O2 (21 mmol) was gradually added into the reactor at room temperature. The obtained mixture was stirred at 30 °C for appropriate time (Table 4). The reaction was monitored by TLC and GC. After completion of the reaction, the catalyst was recovered by filtration. Evaporation of the solvent under reduced pressure gave the crude product. Further purification was achieved by flash column chromatography on a silica gel (petroleum ether/ethyl acetate, 5:1) to give the desired product. Fresh substrates were then recharged to the recovered catalyst and then recycled under identical reaction conditions. |
80% | Stage #1: 4-nitrobenzyl chloride With sodium azide; (4s,6s)-2,4,5,6-tetra(9H-carbazol-9-yl)isophthalonitrile; zinc trifluoromethanesulfonate In acetonitrile at 25℃; Irradiation; Stage #2: With trifluorormethanesulfonic acid In acetonitrile for 1h; | |
79% | With copper(II) choride dihydrate; ammonium formate; potassium carbonate In neat (no solvent) at 135℃; for 24h; Sealed tube; Schlenk technique; Green chemistry; | |
76% | With copper(II) perchlorate hexahydrate; trimethylsilylazide; 2,3-dicyano-5,6-dichloro-p-benzoquinone In 1,2-dichloro-ethane at 60℃; for 48h; | |
74% | With 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; ammonium acetate; oxygen; nitric acid; acetic acid at 50℃; for 12h; Sealed tube; | 2.1 Experimental procedure for the aerobic conversion of benzyl alcohols to aromatic nitriles General procedure: 0.5 mmol substrate, 1.5 mmol NH4OAc, 0.15 mmol TEMPO, 2 mL AcOH and 0.15 mmol HNO3 weresuccessively added to a dried 45 mL tube filled with 1atm oxygen. Then the reaction tube was sealed andplaced in a constant-temperature oil bath to perform the reaction for 12 h. Once the reaction time wasreached, the mixture was cooled to room temperature. Then the mixture was alkalized to pH 7-8 with sodiumhydroxide aqueous solution. GC analysis of organic phase provided the GC yields of the products.Subsequently, the crude product from another parallel experiment was purified by column chromatography,and identified by 1H-NMR, 1C-NMR or GC-MS |
70% | With tert.-butylhydroperoxide; ammonia; potassium iodide In water at 20℃; for 15h; | |
45% | With ammonium hydroxide; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; [{(MeOH)Cu(OAc)}(μ-k2:k1-2-(3-(pyridin-2-yl)-1H-pyrazol-1-yl)acetic acid(-H))]2*0.5H2O; tetraethylammonium iodide; oxygen; potassium carbonate In water at 80℃; for 24h; | |
With ammonia; oxygen In tetrahydrofuran at 120℃; for 6h; | ||
> 99 %Chromat. | With ammonium hydroxide; oxygen In tert-Amyl alcohol at 130℃; for 18h; | |
With 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; copper(II) nitrate trihydrate; ammonia; oxygen In water; dimethyl sulfoxide at 80℃; for 8h; Sealed tube; | Cu(NO3)2-catalysed one-pot synthesis of 5-phenyl-1H-tetrazole directly from benzylic alcohols; general procedure General procedure: Cu(NO3)2·3H2O (0.10 mmol), TEMPO (0.10 mmol), the benzylicalcohol 3 (1.0 mmol) and DMSO (1 mL) were added to a 100 mLround-bottomed flask equipped with a magnetic stirrer. The vesselwas flushed with O2 and aqueous NH3 (25-28%, 3.0 mmol) was added.The vessel was sealed and the reaction mixture was stirred in an oil bath at 80 °C for 8 h. After cooling to room temperature, the stopper wasremoved and NaN3 (2.0 mmol) was added. Stirring was continued in anoil bath at 120 °C for 16 h. After completion of the reaction, the reactionwas acidified HCl (3 M, pH 1.0). Ethyl acetate (~30 mL) was added,and the mixture was stirred until no solid was present. The organiclayer was separated, and the aqueous layer was extracted with ethylacetate twice. The combined organic layers were washed with saturatedbrine, and concentrated in vacuo. The residue was purified by columnchromatography (silica gel, EtOAc-PE) to afford the product 2. | |
Multi-step reaction with 3 steps 1: potassium carbonate; fluorosulfonyl fluoride; dimethyl sulfoxide / 12 h / 20 °C 2: hydroxylamine hydrochloride; potassium carbonate / 20 °C 3: potassium carbonate; fluorosulfonyl fluoride / 12 h / 20 °C | ||
70 %Chromat. | With ammonium hydroxide; periodic acid; potassium iodide at 60℃; for 131490h; Green chemistry; Sealed tube; | |
100 %Chromat. | With ammonium hydroxide; oxygen In tert-Amyl alcohol at 120℃; for 20h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With 1H-imidazole; iodine; chloro-diphenylphosphine In dichloromethane for 5.5h; Reflux; | |
88% | With [Cp*Ir(NH3)3][I2] In water for 14h; Under air; Reflux; | |
86% | With potassium carbonate In toluene at 110℃; for 40h; |
84% | With sodium hydrogencarbonate In toluene at 110℃; for 17h; | |
80% | With bis(3,5-di-(tert-butyl)-2-hydroxyazobenzolato)nickel(II); potassium <i>tert</i>-butylate In toluene at 130℃; for 36h; | |
78% | With Fe3O4/FeO In water at 40℃; for 1h; Green chemistry; | General procedure for the N-alkylation reaction General procedure: In a typical reaction, a suspension of amine (1.0 mmol) and alcohol (1.0 mmol) was added to a mixture of magnetic catalyst (0.04 g) with 1.5 ml distilled water. The resulting mixture was heated to 40 °C for an appropriate time under aerobic conditions. In the case of exposure by EMF, the resulting mixture was transferred to a Helmholtz cylinder permanent magnet and exposed with 362 μT intensity for an appropriate time. Progress of the reaction was monitored by TLC. After completion of the reaction, the mixture was cooled to room temperature, and the catalyst was separated from the product solution using an external magnet, washed with deoxygenated distilled water, dried in a desiccator at room temperature, and used for the next reaction cycle without any pre-treatment. Solvent of the reaction mixture was evaporated to generate the crude product. The product was concentrated and purifiedby column chromatography on silica-gel using EtOAc/heptane (1:4) as eluent. |
77% | With potassium <i>tert</i>-butylate In toluene at 140℃; | |
68% | With 1,2-bis(5-methylisoxazol-3-yl)hydrazine; triphenylphosphine In acetonitrile for 8.5h; Reflux; | |
With nanosized zeolite Beta at 135℃; Inert atmosphere; Green chemistry; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With potassium fluoride; sulfur(VI) fluoride; triethylamine In acetonitrile at 20℃; for 8h; | 1 Example 1: Preparation of 4-nitrobenzyl fluoride In a 100ml single-necked flask, 3.06g (20mmol) of 4-nitrobenzyl alcohol (formula I, R=4-NO 2 ), 1.16g (20 mmol) of potassium fluoride, 0.66g (6.5 mmol) of triethylamine were successively added and 40ml of acetonitrile were stirred at 20°C for 8h in a sulfonyl fluoride atmosphere. After the reaction was completed, 50ml of water was added to dilute it, and then 50ml of ethyl acetate was added for extraction three times. The organic phases were combined, washed with saturated brine, and anhydrous sulfuric acid. Dry over sodium, filter with suction, and concentrate to obtain 2.84 g of 4-nitrobenzyl fluoride with a purity of 98% and a yield of 90%. |
85% | With alkylfluor; caesium fluoride In toluene at 23℃; for 16h; Inert atmosphere; Schlenk technique; Sealed tube; | |
85% | With caesium fluoride; BRI; 1,3-bis(2,4,6-trimethylphenyl)-4,5-dihydroimidazol-2-ylidene In dichloromethane-d2 at 20℃; for 0.5h; Inert atmosphere; UV-irradiation; |
83% | With Nonafluorobutanesulfonyl fluoride; triethylamine In acetonitrile at 25℃; for 24h; | 2-2. Equation (b) in Scheme 2. The procedure for the reaction of 4-nitrobenzyl alcohol (1a) with n-C4F9SO2F to synthesize 4-nitrobenzyl fluoride (8) At 25 °C, n-C4F9SO2F (1.82 g, 6.0 mmol, 2.0 equiv.) was slowly dropped via a syringe into a solution of 4-nitrobenzyl alcohol (1a, 0.46 g, 3.0 mmol) and Et3N (0.60 g, 6.0 mmol, 2.0 equiv.) in 10 mL of CH3CN within 5 min. The solvent was kept to stir at 25 °C for 24 h. The solvent was evaporated to remove volatile ingredients under reduced pressure. The resulting residue was dissolved in 30 mL of EtOAc and washed with water (2×10 mL) and brine (10 mL). The organic layer was dried over anhydrous Na2SO4. Filtration and concentration in vacuo provided residue which was purified through silica gel flash column chromatography using Hexane/EtOAc (50:1, v/v) as eluent generating 0.38 g of 8, colorless oil, yielding 83% p-nitrobenzyl fluoride (8): 83% yield, colorless oil. 1H NMR (400 MHz, CDCl3) δ 8.19 (d, J = 8.4 Hz, 2H, ArH), 7.49 (d, J = 8.0 Hz, 2H, ArH), 5.48 (d, 1JF-H = 46.8 Hz, 2H, ArCH2F); 13C NMR (101 MHz, CDCl3) δ 147.81, 143.45 (d, 2JC-F = 18.0 Hz), 127.03 (d, 3JC-F = 7.0 Hz), 123.74, 82.88 (d, 1JC-F = 170.0 Hz). |
82% | With 2-tert-butyl-1,1,3,3-tetramethylguanidine; 4-(methylsulfonyl)phenyl sulfurofluoridate In toluene at 20℃; for 20h; | |
77% | Stage #1: 4-Nitrobenzyl alcohol With copper chloride (I); diisopropyl-carbodiimide at 60℃; for 1h; Microwave irradiation; Sealed tube; Stage #2: With copper difluoride In water monomer at 100℃; for 24h; Microwave irradiation; | |
71% | With 1,2-Diiodoethane; triphenylphosphine; caesium fluoride In N,N-dimethyl-formamide at 100℃; for 2h; Sealed tube; Inert atmosphere; | |
70% | With diethylamino-sulfur trifluoride In dichloromethane at 70℃; for 0.266667h; | |
63% | Stage #1: 4-Nitrobenzyl alcohol With 1,2,3-Benzotriazole; thionyl chloride In dichloromethane Stage #2: With potassium fluoride In dichloromethane; N,N-dimethyl-formamide for 11h; | |
45% | With pyridine-2-sulfonyl fluoride; 1,3,4,6,7,8-hexahydro-1-methyl-2H-pyrimido[1,2-a]pyrimidine In toluene at 20℃; for 48h; | |
Multi-step reaction with 2 steps 1: triphenylphosphine; bromine / dichloromethane / 1.5 h / 21 °C 2: n-tetrabutylammonium fluoride trihydrate / acetonitrile / 18 h / 20 °C | ||
With diethylamino-sulfur trifluoride In dichloromethane at -78 - 20℃; for 1h; | ||
Multi-step reaction with 2 steps 1: triphenylphosphine; bromine / dichloromethane / 18 h / -78 - 20 °C / Inert atmosphere 2: n-tetrabutylammonium fluoride trihydrate / acetonitrile / 18 h / Inert atmosphere |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
79% | In toluene; for 3h;Heating / reflux; | Example 4 Preparation of (2S,3aS,7a5)-octahydroindole-2-carboxylic acid p-nitrobenzylic ester p-toluenesulfonate In a 1 L flask with mechanical stirring and equipped with a Dean-Stark apparatus were mixed 40 g of (2S,3aS,7aS)-octahydroindole-2-carboxylic acid (0.236 mmole), 40 g of p-nitrobenzyl alcohol (~1.1 mol. eq.), 54 g of p-toluenesulfonic acid (1.2 mol. eq.) and 400 mL of toluene. The reaction was heated under reflux for 3 hours while water was removed by azeotropic distillation with a Dean-Stark apparatus. The reaction was cooled to room temperature then 400 ml of isopropanol were added and the solution was stirred at 0-5C for 1 hour. The solid was removed by filtration, rinsed with isopropanol and dried at 50C in vacuo for one night to give 89 g of ester (79%). NMR-1H: 8.28 (d, J = 8.6, 2H arom. APTS), 7.71 (d, J = 8, 2H arom. Bn), 7.68 (c, J = 8.6, 2H arom. APTS), 7.24 (d, J = 8, 2H arom. Bn), 5.44 (m, CH2 Bn), 4.59 (bt, J = 8.4, H), 3.73 (m, 1H), 2.53-2.45 (m, 2H), 2.37 (s, CH3 APTS), 2.28-2.17 (m, 1 H), 1.98-1.90 (m, 1 H), 1.76-1.36 (m, 7H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | With tert.-butylhydroperoxide; ammonia; oxygen In water monomer; N,N-dimethyl-formamide at 80℃; for 5h; Green chemistry; | |
95% | With hydroxyamino hydrochloride; dihydrogen peroxide; potassium carbonate In water monomer at 80℃; for 20h; | |
95% | With hydroxyamino hydrochloride; dihydrogen peroxide; potassium carbonate In water monomer at 80℃; Green chemistry; |
90% | With tert.-butylhydroperoxide; ammonium hydroxide In water monomer at 100℃; for 16h; | |
88% | With tert.-butylhydroperoxide; 1-(3-sulfopropyl)pyridinium phosphotungstate; ammonia In water monomer at 90℃; for 1h; Microwave irradiation; Green chemistry; | 21 4.3. Typical procedure for the synthesis of amides by HPAIL scatalyzed tandem oxidative amidation General procedure: [PyPS]3PW12O40 (0.14 g, 0.04 mmol) and TBHP (0.78 g, 3.0 equiv., 70% aqueous solution) were added to a mixture of alcohol (2 mmol) and amine (2.4 mmol) in a 15 mL a glass pressure tube. After the pressure tube was closed, the reaction mixture was stirred at 90 °C under MW (700 W). The progress of the reaction was monitored by TLC. After the reaction is completed, the aqueous reaction mixture was concentrated under reduced pressure, the remaining mixture was diluted with ethyl acetate (20 mL) with stirring for 30 min. The insoluble catalyst was recovered by filtration or centrifugation. The filtrate was evaporated and the residue was directly purified by recrystallization or column chromatography to give amide product. |
81% | With ferric(III) chloride; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; hydroxyamino hydrochloride; iodine; potassium carbonate In 1,2-dichloro-ethane at 90℃; for 24h; | |
70% | Stage #1: 4-Nitrobenzyl alcohol With ammonia; iodine In water monomer at 60℃; for 3h; Stage #2: With ammonia; dihydrogen peroxide In water monomer at 0 - 20℃; | |
Multi-step reaction with 2 steps 1: cesium carbonate; styrene / iridium pentamethylcyclopentadienyl dichloride dimer / toluene / 36 h / 111 °C 2: 80 mg / hydroxylamine hydrochloride / iridium pentamethylcyclopentadienyl dichloride dimer / toluene / 16 h / 111 °C | ||
99 %Chromat. | With ammonium hydroxide; cryptomelane; oxygen In 1,4-dioxane at 130℃; for 3h; Autoclave; Green chemistry; | |
With oxygen; urea In <i>tert</i>-butyl alcohol at 140℃; for 6h; Autoclave; Sealed tube; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97% | With triethylamine; In dichloromethane; at 0 - 20℃; for 3.0h; | 4-Nitrobenzyl alcohol (1.53 g, 10 mmol) was introduced into a round bottomedflask, and dichloromethane (10 mNo. ) was added thereto. After the solution was cooledusing an ice bath, diketene (1.26 g, 15 mmol) was slowly added, and triethyknine(0.14 m-6 , 1 mmol) was added. This solution was warmed to room temperature, stirredfor 3 hours, and water (10 m-6 ) was added. The organic kyer was dried over MgSOand distilled under reduced pressure to give 4-nitrobenzyl acetoacetate (2.30 g,Yield=97%). The resulting 4-nitrobenzyl acetoacelate was reacted according to thesame procedure as Example 1 to give the title compound in the yield of 68% (2.09 g).1 H NMR(CDC1): 5 8.25(d, 2H), 7.53(s, 1H), 7.5l(d, 2H), 6.57(s, 1H), 5.27(s,32H), 4.21(s, 2H), 2.54(s, 3H)MS(M+1): 308 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In dichloromethane; acetonitrile; | Second step Preparation of mono-p-nitrobenzylmalonate A solution of 48 g of Meldrum's acid (0.333 moles) and 48 g of p-nitrobenzyl alcohol (0.314 moles) in 200 ml of acetonitrile is heated for 15 hours in a 500-ml flask kept in an oil bath at 100 C. The solvent is then evaporated in vacuo and the residue is dissolved in methylene chloride (50 ml) and tert-butylmethyl ether (500 ml). After concentrating to 300 ml, the solution is stored in the refrigerator for 6 hours; the resulting solid is collected under vacuum filtration, washed with cold t-butyl methyl ether (50 ml) and air dried (50.46 g; 67%; m.p. 97-98 C.). Concentration of the mother liquor to 100 ml affords after one night in the refrigerator a second crop (10.9 g, 14.5%; m.p. 97-99 C.). The mother liquor is extracted with 10% potassium bicarbonate (100 ml), and after filtration on celite the aqueous phase is acidified to pH 3 with 8% hydrochloric acid. The resulting solid is filtered under vacuum, washed with a liberal amount of cold water and air dried. This third crop consists of 10.37 g (13.8%); M.p. 99-100 C. Total yield 71.73 g, 95 %. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
59% | With malonic acid; toluene-4-sulfonic acid; In toluene; | a) Preparation of mono-p-nitrobenzyl malonate by esterification of malonic acid with p-nitrobenzyl alcohol: A mixture of 27.5 g of p-nitrobenzyl alcohol, 28.1 g of malonic acid, 0.4 g of p-toluene sulfonic acid and 180 ml of toluene was heated to reflux (from 100 to 115 C.) for 6 hours in a 300 ml flask. During this period, the water formed was separated as the toluene azeotrope. The reaction mixture was cooled to room temperature, and thus formed precipitates were collected by filtration, washed with toluene and dried to give 48 g of crude mono-p-nitrobenzyl malonate (crude yield: 59%, purity: 52.9%) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
0.95 g (52%) | 4-Nitrobenzyl 5-amino-4-oxopentanoate Hydrochloride [Compound 11] From 4-nitrobenzyl alcohol (5.0 g; 33 mmol) and <strong>[5451-09-2]5-amino-4-oxopentanoic acid hydrochloride</strong> (1.0 g; 6.0 mmol). The reaction was complete after 15 min at 135 C. The yield was 0.95 g (52%). 1H NMR (200 MHz; DMSO-d6): delta 2.72 (2H, t, J=5.8 Hz), 2.91 (2H, t, J=6.2 Hz), 4.02 (2H, br s), 5.28 (2H, s), 7.67 (2H, d, J=8.0 Hz), 8.25 (2H, d, J=9.1 Hz), 8.58 (3H, br s). 13C NMR (50 MHz; DMSO-d6): delta 27.1, 34.3, 46.5, 64.4, 123.5, 128.3, 143.9, 146.9, 171.8, 202.5. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | With air; Fe3O4 fabricated ZnO doped WO3 nanoparticle In ethanol at 20℃; for 2.5h; Irradiation; Green chemistry; | |
98% | With coomassie brilliant blue (CBB) coated on n-propylamine functionalized W-ZnO nanoparticles In ethanol at 25℃; for 2h; UV-irradiation; Green chemistry; | |
94% | With [2,2]bipyridinyl; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; copper chloride (I) In neat (no solvent) at 20℃; for 11h; Green chemistry; |
93% | With Ni0.5Co0.5Fe2O4 supported on arginine-grafted graphene oxide nanocomposite; air In acetonitrile at 80℃; | |
91% | In neat (no solvent) at 150℃; for 24h; Green chemistry; | General procedure General procedure: Reactions were performed in a magnetically stirred round bottomed flask fitted with acondenser and placed in a temperature controlled oil bath. 1,2-Diamine (2 mmol)was added to alcohol (3 mmol) and the reaction mixture was allowed to stir at 135°C in an open (air) atmosphere. After disappearance of the diamine (reaction was monitored by TLC)or after the appropriate time, the reaction mixture was cooled to roomtemperature. The crude residue was further purified by column chromatography using silica gel (100-200 mesh) to afford pure products. All the products wereidentified on the basis of NMR and mass spectral data |
90% | Stage #1: 4-Nitrobenzyl alcohol With iodine; potassium carbonate In <i>tert</i>-butyl alcohol at 50℃; for 2h; Stage #2: 1,2-diamino-benzene In <i>tert</i>-butyl alcohol at 70℃; for 3h; Further stages.; | |
90% | With copper(II) bis(2,4-pentanedionate) In dimethyl sulfoxide at 20℃; for 6h; | 6 Example 6: Add o-phenylenediamine (1.0 mmol), 4-nitrobenzyl alcohol (1.2 mmol), Cu (acac) 2 (0.02 mmol) in sequence to the reaction tube, and then add 2 mL of solvent DMSO,The reaction was carried out at room temperature for 6 hours. After the reaction was completed, the reaction solution was concentrated.The corresponding product was obtained by column chromatography and the separation yield was 90%. |
88.2% | With N-hydroxyphthalimide; oxygen; 1,8-diazabicyclo[5.4.0]undec-7-ene at 100℃; for 10h; Green chemistry; | |
86% | With Fe2(SO4)3; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical In neat (no solvent) at 110℃; for 20h; Green chemistry; | Typical procedure for aerobic oxidative synthesisof benzimidazoles, benzoxazoles, or benzothiazoles General procedure: A mixture of 6 mmol of the alcohol or the amine and5 mmol o-phenylenediamine, o-aminophenol or o-aminothiophenol,10 mol % Fe2(SO4)3, 10 mol % TEMPO wasprepared in a 10 ml three-necked flask, and then stirred inopen air at 110 °C for several hours, The reaction progresswas monitored by TLC. When the final reaction mixturecooled to room temperature, the crude products was directlypurified by column chromatography on silica gel using hexane/ethyl acetate (7:3) as eluent to afford the pure product. |
86% | With bis(3,5-di-(tert-butyl)-2-hydroxyazobenzolato)nickel(II); potassium-t-butoxide; oxygen In toluene at 80℃; for 10h; | |
85% | With copper(II)-manganese(II) bimetallic complex immobilized on magnetite nanoparticles; air In neat (no solvent) at 70℃; for 4h; Green chemistry; | 2.5 General Procedure for Domino One-Pot Preparation of Benzimidazole and Biginelli Derivatives Catalyzed by Fe3O4(at)Cu-Mn General procedure: The one-pot synthesis of benzimidazole carried out in around-bottom flask with benzyl alcohol (1.2mmol) and ortho phenylenediamine (1.0mmol) using Fe3O4Cu-Mn catalyst (0.008g, 0.280mol% Cu, 0.078mol% Mn), under solvent-free and aerobic conditions at 70°C. The reaction mixture was monitored with TLC. Upon reaction completion, the catalyst was magnetically separated, then the product was extracted to dichloromethane (3 × 5mL).The organic layers were combined, dried over Na2SO4 and purified by silica-gel column chromatography (n-hexane:EtOAc = 10: 5). |
85% | In acetonitrile Irradiation; Inert atmosphere; | 2.3 Catalytic reactions The photocatalytic synthesis of benzimidazole was investigaded by using Co-TiO2 catalyst under solar light irradiation. In a typical experiment, orthophenylene diamine (0.226g, 1.66mmol) was dissolved (5ml solution of benzyl alcohol (0.213g, 1.75mmol) in acetonitrile (5ml), and 50mg of photocatalyst was added to 100ml quartz photo reactor. Prior to photoirradiation, the suspensions were magnetically stirred while the reactor was purged with nitrogen gas for 20min to generate inert atmosphere in the photo reactor. The photocatalytic reaction was carried out under solar light irradiation and the reaction mixture was magnetically stirred during the entire period (8h) of experiment. The progress of the reaction was monitored with TLC. After completion of the reaction, the photocatalyst was separated by centrifugation. The mixture was treated with ethyl acetate and then concentrated in vacuo. The residue was purified by silica-gel column chromatography with ethyl acetate/hexane (1:4) to afford the product. |
85% | With oxygen In N,N-dimethyl-formamide at 120℃; for 8h; | |
81% | With anhydrous sodium carbonate In neat (no solvent) at 120℃; Green chemistry; | Catalyst Usage for the dehydrogenative coupling General procedure: Typically, o-phenylenediamine (1.3 mmol) or 2-aminothiophenol (1 mmol), benzyl alcohols (1 mmol), Na2CO3 (20 mol%), and Pd-NPs/Cu2(BDC)2(DABCO) (20 mg, 0.01 mol%) were added to a round-bottom flask. The reaction mixture was heated to 120 °Cand stirred at for the appropriate time in air (TLC monitoring). Ethyl acetate was added to the reaction mixture and catalyst was filtered. For the purification of impure products, chromatography on silica gel was performed (EtOAc:Hep. (1:6)). The entire products characterized by melting point, CHN, 1H-NMR and13C-NMR spectroscopy. |
68% | Stage #1: 4-Nitrobenzyl alcohol With N-hydroxyphthalimide; Mo72V30; oxygen In ethyl acetate at 70℃; for 8h; Stage #2: 1,2-diamino-benzene In ethyl acetate | |
67% | With cobalt sulphate heptahydrate; lithium perchlorate; trifluoroacetic acid In water monomer; acetonitrile at 50℃; for 6h; Electrochemical reaction; | |
With C89H124Cl3IrN2P2Ru; sodium hydroxide In 1,4-dioxane at 110℃; for 18h; Inert atmosphere; Schlenk technique; | 19 Embodiment 19 2 - nitro phenyl -1HSynthesis of benzimidazole -: in an inert gas (such as high-pure nitrogen) under the protection, to 10 ml of the reaction tubes to join Schlek 0.04mmol ruthenium iridiumdifferent nuclear ring metal compound 21, 1.0mmol O-phenylendiamine, 1.7mmol P-nitro benzyl alcohol, 0.7mmol sodium hydroxide and 3 ml of dioxane, replace the nitrogen reaction tube 3 times, then in the oil bath for magnetic stirring under heating to 110 °C, reaction reflux 18 hours. To remove the oil bath, water bath to room temperature; to responds fluid Canada 3 ml water, for 5 ml of dichloromethane extraction three times, and the combined organic phase with anhydrous MgSO4Drying 30 minutes, filtered; the filtrate using a rotary evaporator concentrated, petroleum ether/ethyl acetate to residual liquid as developing agent, silica gel thin layer chromatography separation, to obtain the pure product 2 - nitro phenyl -1H- Benzimidazole, yield 81%. | |
With N-hydroxyphthalimide at 70℃; for 3h; | 2.2.1 General Procedure for Synthesis of Benzimidazole from Benzyl Alcohols and o-Phenylenediamines General procedure: To a mixture of benzyl alcohol (1.2mmol), 1,2-phenylenediamine(1mmol) and NHPI (5mol%) in a glass test tube(10cm tall × 1cm diameter) was added TiO2/AA/Co nanocatalyst(0.06mol%) and the reaction mixture was heatedat 70°C under air, visible light and solvent free conditions.The reaction progress was monitored by TLC. After 3h,ethanol (5mL) was added to the mixture and then TiO2/AA/Co nanocatalyst (solid phase) was separated by centrifugingfollowed by decantation (3 × 5mL ethanol). Desired product(liquid phase) was extracted by plate chromatography elutedwith n-hexane/EtOAc (10/2). Assignments of products weremade by 1H NMR spectral data in comparison with authenticsamples. | |
54.1 %Chromat. | With oxygen In acetonitrile at 27.8℃; for 24h; Irradiation; Green chemistry; | |
With porous borocarbonitride In N,N-dimethyl-formamide for 48h; Inert atmosphere; Irradiation; Green chemistry; chemoselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With Au/Zn0.02Al2O3 In toluene at 60℃; for 7h; | 2.2. Catalytic reaction General procedure: Oxidative coupling of alcohols and amines was performed in aWP-TEC-1020HC parallel reactor provided by WATTCASTM (WATTECSLAB EQUIPMENT CO., LTD.). In a typical protocol, 0.5 mmolbenzyl alcohol, 0.75 mmol aniline, 5 mL toluene and 40 mg catalystwere added successively. And then the reaction mixture was stirred (900 rpm) at 60 C under air (1 atm) for 8 h. The tube wasimmediately cooled in ice water and the reaction mixture wasanalysed using a Thermo Scientific TRACE 1310 gas chromatograph(GC) equipped with a flame ionization detector (FID) and a TR-5column (30 m 0.32 mm 0.25 lm). The quantification was carriedout using the external standard method. A series of toluenesolutions in different concentrations of benzyl alcohol, benzaldehydeor benzylideneaniline were used as external standard, respectively.Each reaction was at least repeated twice to guarantee areproducible result. The conversion of benzyl alcohol, the selectivityto alkylamines and the yield of imine were calculated, on thebasis of a carbon balance. For the reusability test, the catalystwas separated by centrifugation (8000 rpm for 10 min), washedthree times in turn with ethanol (100 mL) and water (100 mL),dried at 50 C for 24 h under vacuum, and was used for the nextrun. |
99% | With cerium(IV) oxide In toluene at 60℃; for 4h; | |
98% | With oxygen In toluene at 80℃; for 24h; Schlenk technique; | 11 Catalyst preparation As described in Example 1,The Schlenk flask was charged with 1 mmol4-nitrobenzyl alcohol and 1 mmol of aniline,0.125 g MnOx / HAP,2mL toluene as solvent,The air ball is an oxygen source,The reaction was stirred at 80 & lt; 0 & gt; C24h,To give the corresponding imine,The conversion was 99%The yield was 98%. |
97% | With tetreamethyl ammonium hydroxide In lithium hydroxide monohydrate; toluene at 80℃; for 12h; | |
95% | With C30H24AgBr4N8(1+)*AgBr2(1-); N,N,N-trimethylbenzenemethanaminium hydroxide In toluene at 20℃; for 12h; Molecular sieve; Schlenk technique; | |
92% | With nanosized zeolite Beta; air at 135℃; for 21h; Green chemistry; | |
92% | With CeO2 nanorods anchored on mesoporous carbon; air In toluene at 80℃; for 2h; | |
90% | With Cu/Al2O3 In para-xylene at 140℃; for 24h; Inert atmosphere; | 5 Example 5 General procedure: 0.5 mmol of the alcohol of the structure shown in the following table and 0.5 mmol of the amine of the structure shown in the following table were added to the reaction flask.The Cu/Al2O3 (20 mol%) obtained in Example 1 and 5 ml of p-xylene were prepared.Under the condition of nitrogen protection, the temperature is raised to 140 ° C, and the sample is detected. The detection method is the GC method with twelve n-hexane as the internal standard. After the reaction is finished, the reaction solution is filtered.The filter cake was washed with toluene (3×5 mL), and washed with K 2 CO 3 (3×5 mL).The filtrate was concentrated and purified by column to give the desired product. The experimental results are as follows: |
85.6% | With air; Mg-Al acid-base bifunctional oxide catalyst In toluene for 12h; | 2.3. Catalyst screening General procedure: Catalytic screening for the oxidative coupling of alcohols andamines was carried out as follows: a 50-mL two-neck flask wascharged with toluene (10 mL), catalyst (0.3 g), 1.0 mmol benzylalcohol and 2.0 mmol aniline. The flask was placed in an 80 °Coil bath and connected with a balloon full of air. The productswere extracted with a sampling pipe equipped with a filter, andthe analyses were performed on a gas-chromatographequipped with an HP-5 column and FID detector. The correspondingalcohols and amines and imines were used as standards. |
65% | Stage #1: 4-Nitrobenzyl alcohol With tert.-butylhydroperoxide; Cu<SUB>2</SUB>(bbda)<SUB>0.5</SUB>(Hbbda)<SUB>1.5</SUB>(OAc)<SUB>1.5</SUB>.8H<SUB>2</SUB>O In neat (no solvent) at 40℃; Stage #2: aniline In neat (no solvent) at 20℃; | |
63% | With 3-(6-(3,5-dimethyl-1H-pyrazol-1-yl)pyridin-2-yl)-1-(2-((1-oxyl-2,2,6,6-tetramethylpiperidin-4-yl)oxy)-2-oxoethyl)-1H-imidazol-3-ium iodide; oxygen; anhydrous sodium carbonate; copper(II) bromide at 100℃; for 24h; Ionic liquid; | |
62% | With iron (ΙΙΙ) nitrate nonahydrate; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; potassium hydroxide In toluene at 80℃; for 36h; Green chemistry; | |
58% | With CdS-SnS2 composite In toluene at 20℃; for 6h; Irradiation; | 2.4. Photocatalytic performance General procedure: The photocatalytic cross-coupling of alcohol and amine was performedas model reaction in a 25 mL round-bottomed flask. Generally,alcohol (0.1 mmol), amine (0.1 mmol) and catalyst (50 mg) wereintroduced into the flask with 1.0 mL of n-hexane as reaction solvent.The mixture was stirred in the dark for 15 min to establish adsorptiondesorptionequilibrium before visible light irradiation. Then, irradiationfor 6 h was executed using a 300 W Xe lamp with a 420 nm cut offfilter (PLS-SXE 300 C). The reaction is maintained at room temperatureand the photon flux inside the reactor was measured to be 0.119 Wcm-2.After reaction, the photocatalyst was resolved through centrifugationand the remaining mixture was analyzed by a Shimadzu GC-2010Pluschromatograph fitted with a capillary SH-Rtx-1701 column. |
6% | With Pd nanoparticles encapsulated inside a MIL100(Fe) cavity In acetonitrile for 24h; Sealed tube; Irradiation; Inert atmosphere; | 2.3. Catalytic reactions General procedure: The Nalkylation reaction was performed in a sealed reactiontube under visible light irradiation. The catalyst (10 mg), amine(0.1 mmol), and alcohol (3 mmol) were suspended in acetonitrile(CH3CN, 2 mL) and the resultant mixture was degassed and saturatedwith N2 to remove any dissolved O2 before the reaction.The reaction was performed under irradiation by a 300W Xe lampequipped with a UVcut filter to remove all irradiation with wavelengths less than 420 nm and an IR-cut filter to remove all irradiationwith wavelengths greater than 800 nm. After the reaction, thereaction mixture was filtered through a porous membrane (20 lmin diameter) and the products were analyzed by GC-MS and GC-FID(Shimadzu GC-2014) equipped with an HP-5 capillary column. |
With Au/HAP; oxygen In toluene at 60℃; for 12h; chemoselective reaction; | ||
98 %Chromat. | With oxygen In toluene at 80℃; for 24h; Green chemistry; | |
With Aluminium grafted mesoporous silica (Al-MCM-41) In neat (no solvent) at 180 - 200℃; for 17h; Green chemistry; | General procedure: General procedure for N-alkylation of amines with alcoholsusing Al-MS | |
With cerium(IV) dioxide; oxygen In para-xylene at 60℃; for 12h; | 2.4. General procedure for the synthesis of imines from alcohols and amines General procedure: In a typical reaction, the catalyst was weighed into a screw-capped glass pressure vessel containing a stir bar. The required amounts of alcohol (0.5 mmol) and amine (0.6 mmol), pre-dissolved in solvent (2 mL), were added and the vessel was filled with oxygen, sealed, and heated to the desired temperature in an oil bath with stirring. The products of the reaction were analyzed by gas chromatography (GC, Agilent 7890A) and GC-mass spectrometry (MS, Agilent 7890A/5975C). | |
With cerium(IV) dioxide In para-xylene at 60℃; for 12h; | 19 In a 15 mL pressure bottle, add 2 mL p-xylene, 5 mmol p-nitrobenzyl alcohol and 6 mmol aniline,0. 1g CeO2, stirring reaction at 60 ° C for 12 h, after the end of the reaction, centrifugal separation, chromatography products, the conversion and selectivity in Table 1. | |
49 %Chromat. | With potassium hydroxide In toluene at 110℃; for 30h; | |
> 99 %Chromat. | With oxygen In toluene at 60℃; for 22h; Green chemistry; | |
With air; Fe2O3 modified CeO2 catalyst In toluene at 60℃; for 9h; | ||
With Cs2CO3 In hexane at 30℃; for 10h; Irradiation; | 2.3. Photocatalytic activity test General procedure: In this experiment, the reaction substrate was 1 mmol of benzylalcohol and 1 mmol of aniline, 1.4 mmol of weakly basic cesium carbonate(Cs2CO3), 50 mg of catalyst, and 6 ml of solvent in a circularbottom flask under an air atmosphere. The substrate was stirred, andthe light reaction was conducted for 10 h. The reaction temperature was30 ± 3°C. | |
With Mg-Al mixed oxide; air at 180℃; for 24h; | ||
With Cs2CO3 In cyclohexane at 15℃; for 10h; Irradiation; | ||
In neat (no solvent) at 60℃; for 12h; Green chemistry; | ||
With MnZr0.5O(y) In toluene at 80℃; for 3h; Green chemistry; | ||
With 3.3 wt% niobium oxide supported on cubic spinel cobalt oxide In neat (no solvent) at 140℃; for 20h; Sealed tube; | 2.3 Catalytic Reactions General procedure: A dehydrogenative coupling reaction was carried out in a35 mL screw-cap Borosil glass test tube. Typically, 1 mmolof alcohol, 3 mmol of aniline, and 25 mg freshly preparedcatalyst were added and tightly screw-capped. The reactiontube was heated to the desired reaction temperaturethrough the oil bath. The reaction mixture was stirredby using a magnetic stirrer. The progress of the reactionwas monitored periodically by withdrawing samples and quantified by Gas Chromatography (Agilent-7890B) andGC-MS (Shimadzu QP-2010, Japan) with HP-5 column,which consists of 5% diphenyl and 95% dimethyl polysiloxanecapillary column and FID as a detector). After thereaction, the solid catalyst was collected by centrifuge,washed with methanol and dried in an oven at 70 °C overnightand reuse for the further cycle. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
40% | 1,4-cubanedicarboxylic acid (2.20 g, 100 mMol) is dissolved in 150 ml oxalyl chloride (Aldrich) containing 20 ing of t-butyl perbenzoate (Aldrich) as an initiator. This is photolyzed for 12 hr with a 250 W low pressure hanovia lamp contained in a quartz immersion well. The temperature is maintained at ca. 5 0C with the aid of a recirculating chiller. The reaction mixture is placed on a rotary evaporator and the oxalyl chloride removed, followed by successive portions of isopropyl acetate to azeotrope away any remaining oxalyl chloride. The bath temperature is maintained below 500C. Cold (0 0C) ethyl acetate (50 ml) contøing p-nitrobeniylTlel>lω^^ mixture is allowed to remain overnight. Solvent (1 L) is removed and the yellow oil is purified by column chromatography on silica gel using Hexane/EtOH ( 6:1) to yield 2.31 g (40% yield) of the pure (one spot on TLQmaterial. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
79.9% | With tetrabutylammomium bromide; potassium iodide at 165℃; for 8.5h; | 11 example 11 A mixture of 7.65 g (0.05 mol) of p-nitrobenzyl alcohol,1.61 g (5.0 mmol) of tetrabutylammonium bromide and 0.17 g (1.0 mmol) of KI were added to a three-necked flask, and the mixture was stirred at 165 ° C for 4 hours. Of triethyl phosphite was added and the reaction was continued at 165 & lt; 0 & gt; C for 4.5 h. After cooling to room temperature, the mixture was extracted with a 1: 3 by volume mixture of ethyl acetate and petroleum ether, and concentrated under reduced pressure to give 16.35 g of product. The yield of p-nitrobenzylphosphonic acid diethyl ester was 79.9%. |
15% | With zinc(II) iodide In tetrahydrofuran for 12h; Inert atmosphere; Reflux; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | With oxygen In dimethyl sulfoxide at 120℃; for 12h; Schlenk technique; Sealed tube; Green chemistry; | General procedure for the synthesis of N-heterocyclic compounds General procedure: A 25 mL Schlenk-type tube equipped with a magnetic stir bar was charged with o-substituted aniline 1a-1f. The reaction tube was evacuated and back-filled with O2. Under oxygen atmospheres, ethers or alcohols 2a-2n and DMSO were added at room temperature, then the reaction mixture was stirred at 120 C for 12 h. The reaction was monitored by TLC. After completion of the reaction, the resulting solution was cooled to room temperature, and neutralized with saturated NaHCO3 aqueous solution. The product was extracted with EtOAc or CHCl3, dried over anhydrous Na2SO4 and concentrated in vacuum. The crude product was purified by flash column chromatography on silica gel to give N-heterocyclic compounds 3. |
83% | With iodine; sodium hydroxide In water at 20℃; for 6h; Electrochemical reaction; Green chemistry; | |
78% | With dipotassium peroxodisulfate In water; acetonitrile at 20℃; for 5h; Electrochemical reaction; Green chemistry; |
75% | With potassium hydroxide In toluene at 90℃; for 24h; | Typical procedure of synthesis of 4(3H)-quinazolinones General procedure: To an oven-dried 20 cm3 test tube with a ground-in stopperequipped with a stir bar were added anthranilamide (1.0 mmol), benzyl alcohol (1.0 mmol), KOH (2.0 mmol),and 4 cm3 toluene. The test tube was put in an oil bath potpreheated at 90 C and the mixture was stirred for 20 h at90 C. After cooling to room temperature, the reactionmixture was added about 5 g silica gel and directly condensedon a rotator under vacuum. The resulting residualwas transferred to a silica gel chromatography column andeluted with a solution of petroleum ether and ethyl acetate[4/1 (v/v)] to give a white solid 2-phenyl-4(3H)-quinazolinone.For some products (3f, 3g, 3n, and 3t) onlysparingly soluble in ethyl acetate, the reaction mixtureswere condensed in vacuo on a rotary evaporator. Theresiduals were washed three times with water and oncewith ethyl acetate, and then dried in an infrared oven togive the desired products pure enough for NMR analysis. |
72% | With Iron(III) nitrate nonahydrate; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; oxygen; potassium hydroxide In toluene at 100℃; for 12h; | |
68% | With tert.-butylhydroperoxide; iron(III) 1,3,5-benzenetricarboxylate In dimethyl sulfoxide at 60℃; for 14h; | |
63% | With potassium <i>tert</i>-butylate; C37H30N3OPPd In toluene at 110℃; for 24h; | |
60% | With potassium hydroxide In para-xylene at 80℃; for 6h; | General procedure for the preparation of 2-(substituted)quinazolin-4(3H)-ones General procedure: In a two-necked flask, a mixture of o-aminobenzamide(1 mmol, 0.14 g), benzyl alcohol (1 mmol) in the presenceof catalyst: 0.05 g (3.10 mol%) for Fe3O4bagasse; 0.05 g(7.90 mol%) for MnO2bagasse; or 0.05 g for MnO2-Fe3O4bagasse, KOH (0.028 g, 0.5 mmol), and p-xylene (5 mL) wereheated for 6 h under stirring conditions and air blowing at80 °C. The progress of the reaction was monitored by TLC.After completion, the catalyst was separated by an externalmagnet and washed with water. After removing the organicsolvents, and crude product was separated to give final product. |
55% | With potassium <i>tert</i>-butylate; Zn(2-((4-chlorophenyl)diazenyl)-1,10-phenanthroline)Cl<SUB>2</SUB>; zinc In toluene at 100℃; for 16h; | |
52% | With C18H11Cl3CuN4; sodium hydroxide In toluene at 90℃; for 36h; | |
50% | With bis[dichloro(pentamethylcyclopentadienyl)iridium(III)] In 5,5-dimethyl-1,3-cyclohexadiene for 120h; Inert atmosphere; Reflux; | |
50% | With (6,8,15,17-tetramethyl-7H,16H-5,9,14,18-tetraaza-dibenzo[b,i]-cyclotetradecenato(2-)-k(4)-N,N',N'',N''')nickel(II); sodium t-butanolate In 5,5-dimethyl-1,3-cyclohexadiene at 100℃; for 36h; Inert atmosphere; Schlenk technique; | |
14% | With oxygen In dimethyl sulfoxide at 160℃; for 7h; | Synthesis of 2-substituted-4(3H)-quinazolinones: 3a-k General procedure: 2-aminobenzamide (1a) (0.5 mmol) and alcohol (2) (2 mmol) were added to an oven-dried glassware with DMSO (1 mL). Then the system was degassed and filled with oxygen. The reaction mixture was stirred and heated to 140°C. Progress of the reactionwas monitored by TLC. After completion of the reaction,the resulting solution was cooled to room temperature, and diluted with dichloromethane, washed with water and brine, dried over anhydrous Na2SO4 and concentrated with the aid of a rotary evaporator. The residue was purified by column chromatography on silica gel using petroleum ether/tetrahydrofuran (5:1 to 2:1) as eluent to provide the desired product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90%; 86% | With per-rhenic acid; In toluene; for 17h;Reflux; | General procedure: In a typical experiment, to a solution of HReO4 (5.0 mol %) in toluene (3 mL) was added the 4-methylphenyl sulfoxide (1.0 mmol) and the alcohol (1.0 mmol). The reaction mixture was heated at reflux temperature under air atmosphere (the reaction times are indicated in the Tables 1-3) and the progress of the reactions was monitored by TLC or 1H NMR. Upon completion, the reaction mixture was evaporated and purified by silica gel column chromatography with n-hexane to afford the carbonyl compounds and 4-methylphenyl sulfide, which are all known compounds. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triphenylphosphine; diethylazodicarboxylate; In tetrahydrofuran; toluene; at 0 - 20℃; | General procedure: Diethyl azodicarboxylate (40percent in toluene, 3.74 g, 8.58 mmol) was slowly added to a stirring solution of cyclohexane ethanol (1.0 g, 7.80 mmol), <strong>[56962-11-9]2-chloro-4-hydroxybenzaldehyde</strong> (1.22 g, 7.80 mmol) and triphenylphosphine (2.25 g, 8.58 mmol) in THF (20 mL) over 10 min. at 0 °C. The mixture was then stirred at room temperature until all of the starting materials dissolved (TLC analysis). The resulting solution was concentrated under reduced pressure and purified by column chromatography over silica gel (elution with hexane/ethyl acetate) to produce 1.80 g of intermediate, 2-chloro-4-(2-cyclohexylethoxy)benzaldehyde (1.64 g, 87percent) as yellow oil. A mixture of 2-chloro-4-(2-cyclohexylethoxy)benzaldehyde (1.0 g, 4.06 mmol), 2,4-thiazolidinedione (475 mg, 4.06 mmol), piperidine (0.20 mL, 2.03 mmol) and acetic acid (0.13 mL, 2.03 mmol) in toluene (20 mL) was then added to a round bottom flask fitted with a Dean?Stark water trap and stirred under reflux for overnight. After cooling to room temperature, the precipitate was washed with hexane and dried to produce compound 1. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | With [2,2]bipyridinyl; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; copper(l) chloride In neat (no solvent) at 20℃; for 12h; Green chemistry; | |
81% | With iron(III) sulfate; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical In neat (no solvent) at 110℃; for 26h; Green chemistry; | Typical procedure for aerobic oxidative synthesisof benzimidazoles, benzoxazoles, or benzothiazoles General procedure: A mixture of 6 mmol of the alcohol or the amine and5 mmol o-phenylenediamine, o-aminophenol or o-aminothiophenol,10 mol % Fe2(SO4)3, 10 mol % TEMPO wasprepared in a 10 ml three-necked flask, and then stirred inopen air at 110 °C for several hours, The reaction progresswas monitored by TLC. When the final reaction mixturecooled to room temperature, the crude products was directlypurified by column chromatography on silica gel using hexane/ethyl acetate (7:3) as eluent to afford the pure product. |
80% | With sodium carbonate In neat (no solvent) at 120℃; Green chemistry; | Catalyst Usage for the dehydrogenative coupling General procedure: Typically, o-phenylenediamine (1.3 mmol) or 2-aminothiophenol (1 mmol), benzyl alcohols (1 mmol), Na2CO3 (20 mol%), and Pd-NPs/Cu2(BDC)2(DABCO) (20 mg, 0.01 mol%) were added to a round-bottom flask. The reaction mixture was heated to 120 °Cand stirred at for the appropriate time in air (TLC monitoring). Ethyl acetate was added to the reaction mixture and catalyst was filtered. For the purification of impure products, chromatography on silica gel was performed (EtOAc:Hep. (1:6)). The entire products characterized by melting point, CHN, 1H-NMR and13C-NMR spectroscopy. |
80% | With di-tert-butyl peroxide In diphenylether at 120℃; for 6h; | 2.2 Catalytic Reactions General procedure: In a representative catalytic experiment, benzyl alcohol(0.135g, 1mmol), 2-aminophenol (0.204mL, 2mmol),and diphenyl ether (0.1mL) as an internal standard weredissolved in xylene (4mL). The solution was added intoa round bottom flask. The Fe-MOF catalyst with pre-calculatedquantity was then introduced to the reactor. Thecatalyst amount was worked out regarding the iron/ benzylalcohol molar ratio. The reaction mixture was stirred undermagnetic stirring for 5min to dispense the catalyst in the liquidphase. Subsequently, di-tert-butyl peroxide (tBuOOtBu,0.63mL, 3mmol) was added dropwise to the reactor. Themixture was magnetically stirred at 120°C for 360min.Samples were taken at different time periods, quenched withNaCl solution (5% w/w, 1mL). The organic ingredients wereafterwards extracted into ethyl acetate phase (3mL), driedwith Na2SO4,and analyzed by GC concerning the internalstandard. The desired product, 2-phenylbenzo[d]oxazole,was isolated by silica gel column chromatography. 1HNMR, 13C NMR, and GC-MS experiments were performedto verify the product structure. To explore the recyclability,the iron-based framework was collected by centrifugation,washed thoroughly with methanol to remove product andexcess reagents, heated under vacuum on a Shlenkline at120°C for 3h, and reutilized for new catalytic experiment. |
75% | With bis(3,5-di-(tert-butyl)-2-hydroxyazobenzolato)nickel(II); potassium <i>tert</i>-butylate; oxygen In toluene at 80℃; for 10h; | |
70% | With cobalt(II) sulphate heptahydrate; lithium perchlorate; trifluoroacetic acid In water; acetonitrile at 50℃; for 6h; Electrochemical reaction; | |
With oxygen In acetonitrile for 10h; Schlenk technique; Sealed tube; Irradiation; Green chemistry; | 2.3. Light-induced reactions General procedure: The synthesis of 2-substituted benzothiazoles from oaminothiophenols and alcohols was performed in a sealed Schlenk tube under visible light irradiation. Typically, a mixture of oaminothiophenol(0.1 mmol) and alcohol (0.3 mmol) in acetonitrile(CH3CN, 2 mL) was saturated with O2 before the mixture wastransferred into a 10 mL tube containing 10 mg of MOFs. The suspensionwas irradiated with a 300WXe lamp equipped with a UVcutfilter to remove all irradiations with wavelengths less than420 nm and an IR-cut filter to remove all irradiations with wavelengthsgreater than 800 nm. After the reaction, the suspensionwas filtered through a porous membrane (diameter 20 μm) andthe products were analyzed by GC-MS and GC-FID (ShimadzuGC-2014) with an HP-5 capillary column. The reaction, scaled upby 10 times, was conducted under similar conditions in a homemadereactor. A mixture of o-aminothiophenol (1 mmol) and benzylalcohol (3 mmol) in CH3CN (20 ml) saturated with O2 wastransferred to the homemade reactor containing 100 mg of MIL-100(Fe). The reactor was irradiated with a 300W Xe lampequipped with both a UV-cut filter and an IR-cut filter. | |
With porous borocarbonitride In N,N-dimethyl-formamide for 48h; Inert atmosphere; Irradiation; Green chemistry; chemoselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97% | With 1,3-dimethylbarbituric acid; potassium hydroxide; In acetonitrile; at 80℃; | General procedure: A mixture of benzyl alcohol (2.50 mmol) with mentioned catalytic systems in the acetonitrile (3 mL) was stirred under air blowing at 80C. The solution of 2-amino pyridine (0.10 g, 1.00 mmol) and cyclohexyl isocyanide (0.11 g, 1.00 mmol) in acetonitrile (2 mL) were added to the reaction mixture and followed by stirring at 80C. The progress of the reaction was monitored by TLC. After the compellation of the reaction, the catalyst was separated by filtering and the solvent was evaporated. The solid residue was washed with deionized water and crystalized in ethanol. |
68% | General procedure: To a solution of (het)aryl methyl alcohol (4.6 mmol) in DMSO (2 mL), T3P (5.5 mmol, 50%solution in ethyl acetate) was added at 0 C followed by triethylamine (9.2 mmol) undernitrogen atmosphere. The mixture was stirred at room temperature for 1.5 h. After completionof the reaction (monitored by TLC), KOH (69.0-92.0 mmol) in water-ethanol (1:1::v;v) mixture (3mL) was added drop wise to the reaction mixture at 0 C and stirred for 5 min followed byTosMIC (5.0 mmol) addition. The reaction was monitored by TLC and evaporated the ethanolfrom reaction mixture under reduced pressure, followed by dilution with ethyl acetate (2 x 25mL). The organic layer was washed with water (2 x 20 mL) and brine solution (2 x 20 mL). Then,the organic layer was dried over anhydrous sodium sulphate and concentrated in vacuum toafford crude product. The crude was purified by column chromatography over silica gel (60-120mesh) using appropriate ratios (8:2) of hexane:ethyl acetate mixture as an eluent. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With iron(III) chloride; TEMPOL; L-valine; oxygen; In toluene; at 60℃; under 760.051 Torr; for 24h;Molecular sieve; Schlenk technique; | General procedure: The preparation of these N-sulfinylimines was performed with 0.4 mmol (±)-sulfinamide and the 1.5 equimolar amount corresponding aromatic alcohol, L-valine(0.04 mmol), FeCl3 (0.04 mmol), 4-OH-TEMPO (0.08 mmol), toluene (2.5 mL), 4AMS (0.7000 g) were added to a 100 mL schlenk tube. Then the resulting mixture wasvigorously stirred under O2 at 60 C for 24 h. After the reaction, the residue wasfiltered off, and the solvent was removed under vacuum to give the crude product,which was purified by column chromatography on silica gel to give the pure product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With Fe3O4/FeO; In water; at 40℃; for 1.5h;Green chemistry; | General procedure: In a typical reaction, a suspension of amine (1.0 mmol) and alcohol (1.0 mmol) was added to a mixture of magnetic catalyst (0.04 g) with 1.5 ml distilled water. The resulting mixture was heated to 40 C for an appropriate time under aerobic conditions. In the case of exposure by EMF, the resulting mixture was transferred to a Helmholtz cylinder permanent magnet and exposed with 362 muT intensity for an appropriate time. Progress of the reaction was monitored by TLC. After completion of the reaction, the mixture was cooled to room temperature, and the catalyst was separated from the product solution using an external magnet, washed with deoxygenated distilled water, dried in a desiccator at room temperature, and used for the next reaction cycle without any pre-treatment. Solvent of the reaction mixture was evaporated to generate the crude product. The product was concentrated and purifiedby column chromatography on silica-gel using EtOAc/heptane (1:4) as eluent. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
81.6% | With triethylamine; In N,N-dimethyl acetamide; at 100℃; for 24h;Cooling with ice; Inert atmosphere; | 18.376 g (0.12 mol) of 4-nitrobenzyl alcohol was added to a 500 ml three-necked flask, 200 ml of N, N-dimethylacetamide and 40 ml of triethylamine and and Reaction (1) <strong>[2351-36-2]naphthalene-2,6-dicarbonyl dichloride</strong> was added slowly under ice bath, magnetic stirring and argon gas, heated to 100C reaction 24h. The reaction solution was poured into a solution of 1000 ml of methanol and water of 1: 1, and a large amount of precipitate was precipitated.The resulting solid was recrystallized from N, N-dimethylformamideand the white solid was collected and dried in a vacuum oven at 50 C for 10 h to give 19.851 g of a white solid in81.6%yield,The intermediate structure is as follows: |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With [2,2]bipyridinyl; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; sodium hydroxide; copper(ll) bromide; In formamide; acetonitrile; at 65℃; for 24h;Schlenk technique; | General procedure: Alcohol (1 mmol), phosphonium salt (1.1 mmol), NaOH (1.1 mmol),CuBr2 (5 mol%), 2,2?-bipy (5 mol%), and TEMPO (5 mol%) were mixed in MeCN and HCONH2 (1:1, 2 mL) in a 100-mL Schlenk tube with an air balloon, and the mixture was stirred at 65 C for 24 h (monitoring by TLC and/or GC-MS). After completion, product was purified by column chromatography (EtOAc and petroleum ether). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With toluene-4-sulfonic acid; In toluene; at 110 - 112℃;Large scale; | In a 1000 L reactor, 84.3 kg of malonic acid, 82.5 kg of p-nitrobenzyl alcohol and 1.2 kg of p-toluenesulfonic acid were charged, and 540 L of toluene was withdrawn.Stirring was started, and the temperature was raised to 110-112 C to reflux, and the generated water was separated by a water separator during the reaction.When no water was produced, the sample was neutralized by liquid chromatography, and the remaining content of p-nitrobenzyl alcohol was detected to be 0.35% by weight, which was less than 0.5% by weight, and the reaction was terminated. The reaction mixture was cooled to 25 C, the mixture was suction filtered, and the filter cake was rinsed with a small amount of toluene and dried.122.42 kg of a mono-p-nitrobenzyl malonate was obtained as a white solid with a molar yield of 95.0% and a purity of 99.2%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With di-isopropyl azodicarboxylate; triphenylphosphine; In tetrahydrofuran; at 0 - 20℃; for 12.5h;Inert atmosphere; | General procedure: To a mixture of triphenylphosphine (18.5 g, 70.4 mmol), 3-nitrobenzylalcohol (7.2 g, 46.9 mmol) and 18b (5.0 g, 23.5 mmol) in THF (300 mL) was added diisopropyl azodicarboxylate (14.2 g, 70.4 mmol) at 0 C. The reaction mixture was stirred at this temperature for 0.5 h under argon. After that, the reaction mixture was allowed to warm to room temperature with stirring for 12 h. The resulting mixture was then concentrated to afford the crude product, which was purified by silica gel column chromatography (eluting with 0-10% MeOH in DCM) to provide 3-bromo-1-(3-nitrobenzyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine as a white solid (6.1 g, 75%). Then to the solid in MeOH (50 mL) was added 0.6 g Pd/C. The reaction mixture was stirred at room temperature for 24 h under hydrogen. After complete conversion of the starting material, the reaction mixture was then filtered by vacuum through celite pad. Solvent was evaporated under vacuum. The resulted product was purified by silica gel column chromatography (eluting with0-10% MeOH in DCM) to provide 9a as a yellow solid (4.3 g, 78%). MS(ESI) m/z: 319.0 [M+H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
54%; 32% | General procedure: 4-methoxybenzyl alcohol 1 (0.27g, 2.00mmol) and TBHP(0.40g, 4.00mmol) were added to mixture of acetonitrile(3.00mL) and CuCl2(0.007g, 0.05mmol). The reactionmixture was stirred for 6h at 70C. Next, TosMIC (0.20g,1.00mmol) and piperidine (0.09g, 1mmol) were pouredinto the reaction flask and stirred for 15min, and then aceticacid (0.06g, 1mmol) was added. After that, this mixturewas heated to 70C for more 6h. At the end of reaction,monitored by thin layer chromatography (TLC), the reactionmixture was diluted with water (5.00mL) and extracted withethyl acetate (3 × 2mL), the resulting solution was purifiedby fash chromatography (ethyl acetate: n-hexane, 1:10). 3a: Colorless liquid. 1H NMR (CDCl3, 300 MHz,delta, ppm): H 1.63 (9H, s, C(CH3)3), 3.90 (3H, s, OCH3),6.93-7.00 (2H, m, Ar), 7.93-7.98 (2H, m, Ar); 13C NMR(CDCl3, 125MHz, delta, ppm): C 28.1, 55.5, 55.6, 84.4, 114.2,131.2, 132.4, 164.1, 164.8, 185.5. MS for C14H17NO5+:calcd.[M]+ 279.1, found 279.1. Elemental Analysis: calcd.C, 60.21, H, 6.14, N, 5.02, found C, 60.21, H, 6.15, N, 5.03. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
48% | General procedure: To a solution of 4-nitrobenzylic acid (1 g, 6.53 mmol) in anhydrous THF (10 mL) was added dropwise lithiumbis(trimethylsilyl)amide (1 M in THF, 7.18 mL, 7.18 mmol) at-78 C under an inert atmosphere. The reaction mixture was stirredaround 5 min at -78 C, and a solution of bis(2-chloroethyl)phosphoramidicdichloride (1) (1.84 g, 7.12 mmol) in anhydrous THF(20 mL) previously cooled at -78 C, was added all at once at the sametemperature (T0). The reaction mixture was stirred at -78 C for30 min, and a solution of 3-(N,N-dimethylamino)propylamine (2 eq.)was added. The reaction was completed after an additional 40 min.These reaction times were determined by 31P NMR monitoring for eachcompound. The reaction was stopped by the addition of water (40 mL)and the reaction mixture was slowly warmed to rt. The aqueous layerwas extracted three times with ethyl acetate (3 × 40 mL). The organiclayers were combined, dried over magnesium sulfate, filtrated andevaporated under reduced pressure. The crude product was purified bysilica gel column chromatography (EtOAc/EtOH, 50/50, v/v + 2%NH4OH) to afford compound 2a (1.64 g, 3.72 mmol) as a yellow-orangeoil. |
Tags: 619-73-8 synthesis path| 619-73-8 SDS| 619-73-8 COA| 619-73-8 purity| 619-73-8 application| 619-73-8 NMR| 619-73-8 COA| 619-73-8 structure
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