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CAS No. : | 89-78-1 | MDL No. : | MFCD00062983 |
Formula : | C10H20O | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | - |
M.W : | 156.27 | Pubchem ID : | - |
Synonyms : |
Racementhol;(±)-Menthol;CCRIS 375;NSC 2603
|
Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P273-P301+P312+P330-P302+P352-P305+P351+P338 | UN#: | N/A |
Hazard Statements: | H302-H315-H319-H335-H413 | 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 |
---|---|---|
99% | With chromium(VI) oxide; potassium chloride; tetrabutyl-ammonium chloride for 0.333333h; | |
98% | With dihydrogen peroxide In water at 65℃; for 2.75h; Green chemistry; chemoselective reaction; | |
97% | With tert.-butylhydroperoxide; dimesityl diselenide In benzene for 17h; Heating; |
97% | With dihydrogen peroxide; 1-butyl-3-methylimidazolium Tetrafluoroborate for 2h; Heating; | |
97% | With pyridine; 1‐methyl‐2‐azaadamantane‐N‐oxyl; 1-chloro-1λ3-benzo[d][1,2]iodaoxol-3(1H)-one In ethyl acetate at 20℃; for 5h; | |
96% | With trichloroisocyanuric acid; silica gel; potassium bromide In dichloromethane at 20℃; for 3h; | |
95% | With 3,5-dimethylpyrazolium fluorochromate(VI) at 20℃; for 0.0333333h; | |
95% | With 1-hydroxy-3H-benz[d][1,2]iodoxole-1,3-dione In ethyl acetate at 80℃; | |
94% | With aluminum oxide; pyridinium chlorochromate In hexane for 5h; Ambient temperature; | |
94.4% | With ruthenium(IV) oxide; tetrabutylammomium bromide; tetra(n-butyl)ammonium hydroxide In water; acetonitrile electrooxidation on Pt electrodes; | |
93% | With pyridine; oxygen In toluene at 80℃; for 2h; | |
93% | With 1-hydroxy-3H-benz[d][1,2]iodoxole-1,3-dione In ethyl acetate for 6h; Heating; | |
93% | With pyridine; 2,2,6,6-tetramethyl-piperidine-N-oxyl; 1,2-Dichloro-3-iodobenzene In chloroform at 50℃; for 0.75h; | |
92% | With peracetic acid; sodium bromide In ethyl acetate at 29.9℃; for 2h; | |
92% | With bis(quinuclidine)bromine(I) bromide In dichloromethane; water for 7h; Ambient temperature; | |
92% | With PFC In dichloromethane at 25℃; for 6h; | |
92% | With air In toluene at 110℃; for 4h; atmospheric pressure; | |
91% | With peracetic acid In tetrachloromethane; dichloromethane at 0℃; for 1h; | |
91% | With imidazolium fluorochromate In acetonitrile at 20℃; for 3h; | |
90% | In various solvent(s) at 100℃; for 28h; | |
90% | With IrH5(P-(i-Pr)3)2 In various solvent(s) at 100℃; for 28h; | |
90% | With Me-IBX In acetone at 20℃; for 1.5h; | |
89% | With dihydrogen peroxide; tetra(n-butyl)ammonium hydrogensulfate In <i>tert</i>-butyl alcohol at 90℃; for 0.5h; | |
89% | With N-Bromosuccinimide; fipronilβ-cyclodextrin In methanol; water; acetone at 20℃; for 12h; | |
89% | With pivaloyl chloride; dimethyl sulfoxide; triethylamine In dichloromethane at -78 - 20℃; for 1h; | |
89% | With oxygen; sodium carbonate In water for 2.66667h; Reflux; | General procedure: A mixture of alcohol (1 mmol), Na2CO3(2 mmol), and Fe3O4SiO2/CuO nanocatalyst (0.04 g) in water was stirred under oxygen at reflux condition. After reaction completion, the catalyst was separated from the reaction mixture by external magnetic field, washed with hot EtOAc (2 × 5 mL), and dried for consecutive reaction runs. Then, the filtrate was cooled to room temperature, quenched with 2 MHCl aqueous solution, filtered, and extracted with dichloromethane. The solvent was evaporated and the organic layer dried over anhydrous Na2SO4. Evaporation of the solvent followed by column chromatography on silica gel (n-hexane/ethyl acetate 9:1 as v/v%) afforded the pure products. |
88% | With oxygen; caesium carbonate In water for 3h; Reflux; | General procedure General procedure: All reactions were performed in a glass flask slurry reactor connected to an O2 tube for atmosphere control and a condenser for reflux condition. A mixture of alcohol (1mmol), Cs2CO3 (0.5mmol) and 2Au/1CuO-ZnO (0.05g) in water was stirred under oxygen atmosphere in a slurry reactor at total reflux condition. Then the catalyst was recovered by filtration, washed two times with 5ml hot EtOAc, and dried for consecutive reaction runs. The filtrate was quenched with 2M HCl aqueous solution, extracted with EtOAc three times and dried over anhydrous MgSO4. Evaporation of the solvent followed by column chromatography on silica gel afforded the pure products (Table3). |
87% | With sodium hydroxide; potassium perrhuthenate for 1h; | |
87% | With aluminium trichloride; benzyltriphenylphosphonium periodate In acetonitrile for 8h; Heating; | |
87% | With N-Bromosuccinimide In methanol; water at 20℃; for 6h; Green chemistry; | General Procedure for Oxidation of Alcohols General procedure: Aromatic alcohol (1-2 mmol) was dissolved in methanol (or acetone in somecases, 2-4 mL) at room temperature, followed by addition of the aqueous solutionof N-bromosuccinimide (1.5 eq.=alcohol) with continuous stirring. GMP-b-CD (3,100mg=mmol of alcohol) were added in the reaction mixture and stirring was continued.Progress of the reaction was monitored by TLC until the reaction was completed(4-6 h). GMP was separated by filtration after completion of the reaction. Thereaction mixture was extracted with ethyl acetate (45 mL), combined organiclayers were dried over Na2SO4, and solvent was removed under reduced pressure.The product was further purified by flash column chromatography and analyzedby NMR spectroscopy. |
86.5% | With acetone at 115℃; | |
86% | With sodium bromite In acetic acid for 5h; Ambient temperature; | |
86% | With fipronilβ-cyclodextrin; 1-hydroxy-3H-benz[d][1,2]iodoxole-1,3-dione In water; acetone at 20℃; for 12h; | |
86% | With copper phthalocyanine; tetra-n-butylammonium hydrogen monopersulfate In water at 85℃; Green chemistry; | |
85% | With potassium chlorochromate In acetone for 3h; | |
85% | With 4-methylmorpholine N-oxide In dichloromethane for 1h; Ambient temperature; | |
85% | With dihydrogen peroxide In benzene at 70℃; for 3h; | |
85% | With oxygen In water at 120℃; for 3h; | |
85% | With bis(chlorine)-1,4-diazabicyclo[2.2.2]octane at 180℃; for 0.0833333h; microwave irradiation; | |
85% | With tert.-butylhydroperoxide; CrO3(3-)*La(3+) at 90℃; for 1h; neat (no solvent); | |
84% | With palladium diacetate; potassium carbonate; triphenylphosphine In toluene for 15h; Heating; | |
84% | With silica gel; bis(trimethylsilyl)chromate for 0.05h; Irradiation; | |
82% | With pyridine; trichloroisocyanuric acid In acetone for 0.333333h; | |
80% | With zinc(II) chlorosulphate In dichloromethane for 2.5h; Ambient temperature; | |
80% | With pyridine; methyl-phenyl-thioether; N,N,N,N-tetraethylammonium tetrafluoroborate In acetonitrile electrochemical reaction: Pt-anode, Pt-cathode, undivided cells, 3F/mol of electrity, 100 mA; | |
80% | With 1-butyl-3-methylimidazolium chloride; 1-hydroxy-3H-benz[d][1,2]iodoxole-1,3-dione at 20℃; for 8h; | |
80% | With N-Bromosuccinimide; ammonium chloride In water; acetonitrile at 80℃; for 2.5h; | |
80% | With air; bis(salicylideniminato-3-propyl)methylamino-cobalt(III); 2,6-dimethoxy-p-quinone In toluene at 100℃; for 2h; | |
79% | With aluminum oxide; sodium bromite In dichloromethane for 24h; Ambient temperature; | |
78% | With 3-carboxypyridinium trifluoroacetochromate In dichloromethane at 20℃; for 1.5h; | |
78% | With 2-chloro-1,3-dimethylimidazolinium chloride; dimethyl sulfoxide; triethylamine In dichloromethane at 20℃; for 24h; | |
76% | With oxygen; isobutyraldehyde In acetonitrile for 3h; Ambient temperature; | |
76% | With <bis(salicylidene-N-methyl 3-hydroxypropionate)>cobalt; oxygen; isobutyraldehyde In acetonitrile | |
75% | With 1-[4-(diacetoxyiodo)benzyl]-3-methylimidazolium BF4; 1-ethyl-3-methylimidazolium tetrafluoroborate In acetonitrile at 30℃; for 18h; | |
75% | With 1,1,3,3-tetramethylguanidinium fluorochromate In dichloromethane for 0.00277778h; Microwave irradiation; | 2.4. General Procedure for the Oxidation under Microwave Irradiation General procedure: The substrate (1mmol) and 1.5-2 mmol oxidant were mixed. To this mixture 0.5 mL CH2Cl2 was added. The mixture was subjected to microwave irradiation (1000 W). Upon completion of the reaction, extraction with ether (3 × 25mL) and evaporation of the solvent gave the corresponding carbonyl compounds. The products formed were analyzed by their 2,4-dinitrophenylhydrazone derivatives.The precipitated 2,4-DNP was filtered off, weighed, and recrystallized from ethanol. |
74% | With HMTAB; silica gel In water at 20℃; for 0.0833333h; | |
74% | With aluminum oxide; quinolinium monofluorochromate(VI) In hexane for 2.5h; Ambient temperature; | |
72% | With oxygen; 2-ethoxycarbonyl-1-cyclopentanone In acetonitrile at 60 - 70℃; | |
71% | With oxygen; sodium acetate In water; dimethyl sulfoxide at 80℃; for 4h; | |
70% | With tetrabutyl-ammonium chloride; dihydrogen peroxide; potassium carbonate In tetrahydrofuran for 120h; Ambient temperature; | |
70% | With quinolinium monofluorochromate(VI) In dichloromethane for 4h; Heating; | |
70% | With hexamethylenetetrammonium fluorochromate In N,N-dimethyl-formamide at 20℃; for 4h; | |
70% | With iodine; potassium carbonate; potassium iodide at 90℃; for 0.75h; | |
69% | With 2,6-dimethylpyridine; methyl octyl sulfide; tetraethylammonium bromide In benzonitrile | |
69% | With 1-hydroxytetraphenylcyclopentadienyl(tetraphenyl-2,4-cyclopentadien-1-one)-μ-hydrotetracarbonyldiruthenium(II) In 1,3,5-trimethyl-benzene at 165℃; for 36h; Inert atmosphere; | |
68% | With [MnIII(2-((2-(2-(2-(2-hydroxybenzylideneamino)phenylamino)propylamino)phenylimino)methyl)phenolato)]Cl; dihydrogen peroxide In acetonitrile for 4h; Reflux; | |
66% | With potassium chlorochromate on alumina In dichloromethane for 73h; Ambient temperature; | |
65% | With 3,5-dimethylpyrazolium fluorochromate(VI) In dichloromethane at 20℃; for 2h; | |
60% | With oxygen; benzaldehyde In 1,2-dichloro-ethane at 80℃; for 36h; | |
58% | With pyridine; N-hydroxyphthalimide; sodium perchlorate In acetonitrile electrolytical oxidation, anode potential 0.85 V; | |
54% | With (carbonyl)(chloro)(hydrido)tris(triphenylphosphine)ruthenium(II); oxygen In toluene at 90℃; for 18h; Molecular sieve; Sealed tube; | |
52% | With tert.-butylhydroperoxide In benzene at 60℃; for 12h; | |
50% | With oxygen; nitrosonium tetrafluoroborate In dichloromethane at 20℃; for 16h; | |
48% | With tetra-N-butylammonium tribromide In acetonitrile at 20℃; for 72h; Irradiation; | 2.2 General experimental procedure for the photocatalytic oxidation of alcohol General procedure: In a 50ml Pyrex round-bottom flask, a mixture of alcohol (1mmol), TBATB (10-20mg, 0.02-0.04mmol) in 10ml of CH3CN was exposed to blue or violet light LED irradiation at room temperature under an air atmosphere with stirring. The progress of the photocatalytic oxidation reaction was monitored by TLC on silica gel plates. The reaction mixture externally irradiated until the alcohol was completely consumed. |
45% | With [(C18H37)2(CH3)2N]3[SiO4H(WO5)3]; dihydrogen peroxide In water; ethyl acetate at 79.84℃; for 10h; | |
33.9% | With tert.-butylhydroperoxide at 70℃; for 5.5h; | |
28% | With tert.-butylhydroperoxide In hexane; water at 50℃; for 16.5h; | |
26% | With tert.-butylhydroperoxide; C14H30Cl2FeN4(1+)*F6P(1-) In [D3]acetonitrile; water; water-d2 at 27℃; for 18h; Inert atmosphere; Schlenk technique; Green chemistry; | |
20% | With dihydrogen peroxide In toluene at 75℃; for 7h; | |
19.2% | With acetone In benzene at 80℃; for 8h; other temperature; | |
19% | With tetrabutylammomium bromide; 1-hydroxy-3H-benz[d][1,2]iodoxole-1,3-dione In dichloromethane; water at 20℃; for 4h; | |
19% | With dipyridinium dichromate; adogen 464; dihydrogen peroxide; sodium carbonate In various solvent(s) for 24h; Heating; | |
With chromium(VI) oxide; acetic acid at 0℃; inactive p-menthanone-(3) from thymomenthol; | ||
With chromic acid l-menthone; | ||
82 % Chromat. | With N-iodo-succinimide; tetra-(n-butyl)ammonium iodide In dichloromethane for 3h; Ambient temperature; | |
With crosslinked poly-4-vinylpyridine hydrobromide In acetonitrile at 50℃; for 21.5h; electric current, 60mA, 10-30V; Yield given; | ||
With phosphorus pentoxide; dimethyl sulfoxide; triethylamine 1.) CH2Cl2, from 0 deg C to RT, 30 min, 2.) CH2Cl2, 0 deg C, 30 min; Yield given. Multistep reaction; | ||
97 % Chromat. | With <MoO(O2)2C5H4N(O)COO>Bu4N In 1,2-dichloro-ethane at 50℃; for 9h; | |
With chromic acid | ||
With ruthenium trichloride; pinane hydroperoxide; <i>tert</i>-butyl alcohol In chlorobenzene for 24h; Ambient temperature; Yield given; | ||
92 % Chromat. | With tert.-butylhydroperoxide In dichloromethane; 1,2-dichloro-ethane at 40℃; for 12h; | |
With aluminum oxide; bromine In dichloromethane for 1h; | ||
With SiW11Zn; dihydrogen peroxide In water at 89.85℃; for 9h; | ||
80 % Chromat. | With CrO3/silica gel In various solvent(s) at 40℃; for 4h; | |
With quinoxalinium fluorochromate In dichloromethane for 0.00416667h; Microwave irradiation; | ||
89 % Chromat. | With chromium(VI) oxide for 0.05h; microwave irradiation; | |
With polystyrene-supported hypervalent iodine(V) reagnet In 1,2-dichloro-ethane at 85℃; for 1h; | ||
90 % Chromat. | With Oxone; sodium chloride In water; ethyl acetate at 20℃; for 1.5h; | |
82 % Chromat. | With Oxone; 2-Iodobenzoic acid; tetra(n-butyl)ammonium hydrogensulfate In ethyl acetate at 70℃; for 6h; | |
With 1,3,5-trichloro-2,4,6-triazine; dimethyl sulfoxide; triethylamine In tetrahydrofuran at -30 - 20℃; for 1.5h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | 3 EXAMPLE 3 EXAMPLE 3 Example 1 was repeated, replacing 2-octanol by (-)-menthol (7.8 g; 50 mmol), increasing the reaction time to 2 hours, and eluding the residue of the organic phase over a column of alumina (instead of silica); 6.78 g (44 mmol) of (-)-menthone were obtained (GLC purity>99%), which corresponds to a 88% yield. | |
88% | 3 EXAMPLE 3 EXAMPLE 3 Example 1 was repeated, replacing 2-octanol by (-)-menthol (7.8 g; 50 mmol), increasing the reaction time to 2 hours, and eluding the residue of the organic phase over a column of alumina (instead of silica); 6.78 g (44 mmol) of (-)-menthone were obtained (GLC purity > 99%), what corresponds to a 88% yield. | |
79.7% | Stage #1: (-)-menthol With pyridine; dichloro-acetic acid; dimethyl sulfoxide In toluene at 25℃; for 0.166667h; Stage #2: In toluene at 23 - 25℃; for 5h; Stage #3: With acetic acid In water; toluene | 7 Example 7 In a reactor equipped with a stirrer, a cooling condenser, a dropping funnel and a thermometer, L-menthol (15.6 g, 0.10 mol), dimethyl sulfoxide (117.2 g, 1.50 mol) and toluene (40 g) were added, and the resulting reaction solution was stirred at a temperature of 20 to 23° C. To this reaction solution, pyridine (7.9 g, 0.10 mol) was added dropwise, followed by dichloroacetic acid (6.4 g, 0.05 mol). The resulting mixture was maintained at a temperature of 25° C. or lower and was stirred for 10 minutes. After stirring, Carbodilite V-03 (manufactured by Nisshinbo Chemical Inc., 431.1 g/mol) (86.2 g, 0.20 mol) was added dropwise to the reaction liquid, while the reaction liquid was maintained at 25° C. or below. After the dropwise addition, the reaction liquid was stirred for 5 hours at 23 to 25° C., and the reaction was terminated with a 1.0% aqueous solution of acetic acid (16 g). After the reaction was terminated, a urea compound precipitated from the reaction liquid was separated by filtration. The filtrate was partitioned to remove the aqueous phase, and then the organic phase was washed with an aqueous sodium chloride solution.The resulting organic layer was treated such that the solvent was removed under reduced pressure, and the residue was distilled under reduced pressure. Thus, menthone (bp: 82 to 85° C./1.33 kPa, 12.3 g, 0.08 mol) was obtained (yield 79.7%). The ketone compound thus obtained was confirmed by using NMR, mass spectrometry and IR spectroscopy. |
Reaktion ueber mehrere Stufen; l-menthone; | ||
at 300℃; beim Leiten ueber Kupfer; l-menthone; | ||
at 300℃; beim Leiten ueber Kupfer; | ||
With styrene; aluminum oxide; copper In toluene at 89.85℃; for 48h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Behandeln der Schmelze mit HCl; <l-menthyl>-chloroacetate; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
48% | With dmap; triethylamine In 1,4-dioxane | |
With dmap; triethylamine In 1,4-dioxane | ||
With N-ethyl-N,N-diisopropylamine In dichloromethane |
With pyridine at 80℃; for 3h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | In toluene Heating; | |
41% | With sodium hydride In 1,4-dioxane for 4h; Heating; | |
18% | Stage #1: (-)-menthol With sodium hydride; potassium iodide In tetrahydrofuran at 0℃; for 0.666667h; Inert atmosphere; Stage #2: chloroacetic acid In tetrahydrofuran at 0℃; for 16h; Reflux; Inert atmosphere; |
10% | Stage #1: (-)-menthol With lithium In tetrahydrofuran for 4h; Reflux; Inert atmosphere; Stage #2: chloroacetic acid In tetrahydrofuran for 20h; Reflux; | |
(i) NaH, DMF, (ii) /BRN= 605438/; Multistep reaction; | ||
(i) Li, (ii) /BRN= 605438/; Multistep reaction; | ||
With sodium 1.) toluene, reflux, 2.) toluene, reflux 2 d; Multistep reaction; | ||
Stage #1: (-)-menthol With sodium In toluene Stage #2: chloroacetic acid |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | With poly(4-vinylpyridine) supported copper(II) oxide nanoparticles; In dichloromethane; at 20℃; for 0.333333h; | General procedure: A mixture of the substrate (1 mmol), 3,4-dihydro-2H-pyran (1 mmol) and PC-NPs (12 mg) in CH2Cl2 (3 drops) was stirred at room temperature. The progress of the reaction was monitored by TLC (EtOAc: n-hexane; 1:1). After completion of the reaction, the mixture was filtered to separate the solid catalyst. Then, the solution was filtered through a silica gel pad and washed with CH2Cl2 (2 × 5 mL). Evaporation of the solvent gave the desired product in high yields. |
60% | In dichloromethane; at 20℃; for 3.0h; | General procedure: A mixture of alcohol or phenol (1 mmol), DHP (1.2-1.4 mmol), and MNPs-PSA (5 mg, 0.95 mol%) was stirred at room temperature in dry CH2Cl2 (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 pure product was isolated by passing of the reaction mixture through a short column using n-hexane and ethyl acetate (9:1) as eluent. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With water 1.) diethyl ether, pyridine, 8-10 degC, 30 min; 2.) diethyl ether, pyridine, allowed to warm to 20 degC; Yield given. Multistep reaction. Yields of byproduct given. Title compound not separated from byproducts; | ||
With water 1.) diethyl ether, pyridine, 8-10 degC, 30 min; 2.) diethyl ether, pyridine, allowed to warm to 20 degC; Yield given. Multistep reaction. Yields of byproduct given; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | at 20℃; for 0.0166667h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With triethylamine In N,N-dimethyl-formamide for 1h; Ambient temperature; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | With sodium hydride In tetrahydrofuran; dimethyl sulfoxide at 25℃; for 12h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With hydrogen Ambient temperature; centrosymmetric crystalline substrate; solid catalyst; conversion rate; other reaction time; other catalyst; | ||
With palladium on activated carbon; hydrogen In methyl cyclohexane at 80℃; for 0.333333h; Flow reactor; Green chemistry; Overall yield = 84 percentChromat.; chemoselective reaction; | H2-FB-slug flow method: General procedure: To a 500 mL Duran bottle was added a solution of phenol derivatives 3 (4.0 mmol)in methylcyclohexane (400 mL). The reactor in which Pd/C (0.95 g, 0.40 mmol) and activated carbon (0.95 g)were charged was placed into the column oven at 80°C. The solution was delivered at a flow rate of 0.7mL/min (residence time in the reactor = 70 s), and H2 gas was delivered at a flow rate of 0.3 mL/min (2 eq).The pressure in front of the reactor was set at approximately 4 MPa to generate FBs. After 30 min of operationunder 0.8 MPa at 80°C, the reaction mixture was collected for 20 min and analyzed by GC-FID withoutpurification. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | With cobalt(II) chloride In acetonitrile at 80℃; for 2h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With [Ru(2-(methylthio)-N-[(pyridin-2-yl)methyl]ethan-1-amine)(triphenylphosphine)Cl2]; potassium <i>tert</i>-butylate; hydrogen In toluene at 80℃; for 3h; | |
95% | With ytterbium(III) triflate In isopropyl alcohol for 74h; Heating; | |
95% | With sodium hydroxide In methanol; dichloromethane at 20℃; for 0.75h; | General experimental procedure. General procedure: To a solution of the ester (1 mmol) in CH2Cl2 (9 mL) was added a methanolicsolution of 3 N NaOH (1 mL, 3 mmol), with the final concentration of the alkali being 0.3 N, and the solventmixture CH2Cl2/CH3OH (9:1, v/v, 10 mL). Esters bearing more than one ester moiety needed more equivalentsof NaOH (Table 1). After stirring, the solution became cloudy and the sodium salt of the carboxylic acid beganto precipitate. The progress of the reaction was monitored by thin layer chromatography (TLC). The mixturewas stirred until the ester was consumed (Table 1), the solvents were then removed under vacuum, theresidue was diluted with water (10 mL) and extracted with ethyl acetate or diethyl ether (2x20 mL) to isolatethe water-insoluble alcohol, and/or to remove unreacted ester. The aqueous phase was cooled, acidified to pH~2 with dilute HCl and extracted with AcOEt (2x20 mL). The combined organic layers were dried (Na2SO4) andthe solvent removed to afford the acid. Alternatively, the RCOONa precipitated during the reaction can beisolated by filtration, washed with CH2Cl2 (10 mL), dried and weighed (Yields: 80-96%). |
91% | With methanol; potassium permanganate at 25℃; chemoselective reaction; | |
90% | With methanol; potassium permanganate; trimethylsulphonium iodide at 25℃; chemoselective reaction; | |
88% | With C15H29MnNO3P2(1+)*Br(1-); potassium <i>tert</i>-butylate; hydrogen In 1,4-dioxane at 120℃; for 48h; Inert atmosphere; Autoclave; | |
63% | With bis(tri-n-butyltin)oxide In toluene at 110℃; for 24h; | |
63% | With bis(tri-n-butyltin)oxide In toluene at 110℃; for 24h; | |
With potassium hydroxide In methanol at 20℃; | ||
50 %Chromat. | With [bis({2‐[bis(propan‐2‐yl)phosphanyl]ethyl})amine](borohydride)(carbonyl)(hydride)iron(II); hydrogen In tetrahydrofuran at 120℃; for 19h; Autoclave; | |
62 %Chromat. | With dichlorido-bis[(2-diphenylphosphino)ethyl]amine-cobalt(II); hydrogen; sodium methylate In 1,4-dioxane at 120℃; for 24h; Autoclave; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | With C15H18BF3; hydrogen; tert-butylimino-tri(pyrrolidino)phosphorane In tetrahydrofuran at 75℃; for 24h; Glovebox; | |
78% | With hydrogen at 80℃; | |
With tri-tert-butoxyaluminum hydride In tetrahydrofuran at 9.9℃; var. temp., ΔG(excit.), ΔH(excit.), ΔS(excit.); |
With isopropyl alcohol for 70h; Heating; Yield given; | ||
With hydrogen In n-heptane at 90℃; for 1.5h; | ||
With [OsCl2(dppb)(Pyme)]; sodium isopropylate; isopropyl alcohol at 82℃; for 0.5h; Inert atmosphere; | ||
93 %Chromat. | With isopropyl alcohol; sodium hydroxide at 80℃; for 26h; | |
With isopropyl alcohol at 150℃; for 5h; Autoclave; High pressure; Inert atmosphere; chemoselective reaction; | The reactions were carried out at 82 °C (the boiling point of PriOH) in standard laboratory glassware or at 150 °C in 300 ml autoclave with magnetic stirring for 5 h under argon atmosphere. The temperature of 150 °C was reasoned by low reactivity of monoterpenoids in the TH reaction.13,16 Monoterpene compound (0.3-0.5 g, 3.2 mmol) dissolved inPriOH (120 ml, 1.5 mol) was mixed with Raney nickel catalyst (0.250 g,~3.8 mmol of nickel) freshly prepared by well-known method based on leaching with aq. NaOH at 50 °C from Raney alloy (Al : Ni = 50 : 50).18 Physicochemical properties of prepared Raney nickel were in goodagreement with reported data.18 BET surface area of the catalyst was50-70 m2 g-1 and did not change dramatically during the reactions. Thus,despite the high nickel-to-substrate molar ratio (1.2 : 1), only about 5% ofall Ni atoms were located on the surface of the catalyst. According to XPS method, the residual aluminum content in the catalyst was 10.3%.X-ray powder diffraction demonstrated the phase of metallic nickel formedfrom Al3Ni and Al3Ni2 intermetallics of initial alloy. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | In neat (no solvent) at 60℃; for 1h; direct acetylation of phenols and alcohols, catalyst reusable without activity loss; | |
100% | In neat (no solvent) at 60℃; for 1h; | |
100% | With polystyrene-bound tetrafluorophenylbis(triflyl)methane |
100% | In nitromethane at 20℃; for 0.25h; | |
100% | With magnesium(II) perchlorate at 20℃; for 0.5h; | |
100% | With N-ethyl-N,N-diisopropylamine In acetonitrile at 20℃; for 3h; | |
100% | With methanesulfonic acid In neat (no solvent) at 30 - 35℃; for 0.166667h; Green chemistry; | |
99% | With Celite; polystyrene-bound super Broensted acid In acetonitrile at 20℃; flow system; | |
99% | With magnesium(II) perchlorate at 20℃; for 1.5h; | |
99% | at 20℃; for 0.5h; | |
99% | With dmap; N-ethyl-N,N-diisopropylamine In acetonitrile at 20℃; for 3.5h; Inert atmosphere; | |
99% | With 2,3-dihydro-5,7-bismethyl-1,4-diazepine monohydroperchlorate In neat (no solvent) at 40℃; for 0.5h; | |
99% | With bis(trifluoromethane)sulfonimide lithium at 35℃; for 48h; | |
99% | With phosphoric acid In acetonitrile at 50℃; for 7h; | |
98% | With aluminum triflate at 20℃; for 0.00555556h; | |
98% | With zinc trifluoromethanesulfonate at 20℃; | General procedure: In a typical experimental procedure, to a mixture of alcohol/phenol (1mmol) and acetic anhydride (1.0mmol) or acyl chloride (1.0mmol) in dichloromethane solvent (2vol) or without solvent, Zn(OTf)2 (0.1mol%) was added. The reaction mixture was stirred at room temperature for the specified time. Completion of reaction was monitored by TLC, after quenching with a saturated solution of NaHCO3 and the products were extracted in to dichloromethane (3×10mL). The combined organic layer was washed with water, dried over anhydrous Na2SO4, and concentrated in vacuum to obtain the product. |
98% | With 4-(dimethylamino)pyridine hydrochloride In toluene at 60℃; for 4h; | |
98% | With zinc trifluoromethanesulfonate In dichloromethane at 25℃; for 0.00277778h; | General procedure for Acetylation General procedure: In a typical experimentalprocedure, to a mixture of alcohol/phenol (1 mmol) and acetic anhydride (1.0mmol) in dichloromethane solvent (2 vol)/without solvent, Zn(OTf)2(0.01-0.1 mol %) was added. The reaction mixture was stirred at roomtemperature for the appropriate amount of time. Completion of reaction wasmonitored by TLC after quenching with a saturated solution of NaHCO3and the products were extracted in to dichloromethane (3 X 10.0 mL). Thecombined organic layer was washed with water, dried over anhydrous Na2SO4and concentrated under reduced pressure. All products were characterized bycomparison of their spectral data and physical prosperities with those ofauthentic samples. |
97% | With bismuth oxide perchlorate at 20℃; for 1h; | |
97% | With 4-N,N-dimethylaminopyridinium saccharinate at 25℃; Inert atmosphere; Neat (no solvent); | |
97% | With 4-N,N-dimethylaminopyridinium saccharinate In neat (no solvent) at 25℃; for 8h; | 4.7. General procedure for the salt-catalyzed esterification General procedure: The alcohol (2mmol) and the anhydride (2.2mmol) were mixed in a 10mL test tube and 1mol% of salt A (0.02mmol) was added. The tube was then capped (or under N2 purge) and the reaction mixture was stirred at room temperature (except for 1-methylcyclopentanol at 60°C). After a couple of hours the acid effluent was evaporated in vacuum. The residue was then allowed to cool to room temperature and the salt was precipitated by adding 2mL hexane (or toluene). After filtration, salt was recovered, and then evaporating solvent from the filtrate afforded the crude ester product. The recovered salt was charged with the substrates, and the reaction mixture was then proceeded to the next run. The products were quantified with GC analysis by comparison to NMP as an internal standard. The products from the 1st run were further purified by column chromatography, and the isolated yields were compared with the GC/MS yields. They were all in good agreement. |
96% | With chloro-trimethyl-silane In acetonitrile for 2h; | |
96% | With trimethylsilyl trifluoromethanesulfonate In dichloromethane at 0℃; for 0.0833333h; | |
96% | In acetonitrile for 6h; Heating; | |
95% | With In(OSO2CF3)3 In acetonitrile at 20℃; for 0.5h; | |
95% | With bismuth(lll) trifluoromethanesulfonate In acetonitrile at 20℃; for 0.333333h; | |
95% | at 20℃; for 0.183333h; | |
95% | at 20℃; for 0.5h; | |
95% | With o-benzenedisulfonimide at 20℃; for 0.166667h; | |
94% | In acetonitrile at 20℃; for 1.25h; | |
94% | With acetonyltriphenylphosphonium bromide at 20℃; for 0.583333h; | |
93% | In hexane at 20℃; for 0.2h; | |
93% | With iron(III) p-toluenesulfonate hexahydrate In acetonitrile at 20℃; for 1.83333h; | Method B (synthesis of an acetate in solvent) General procedure: A suspension of p-nitrobenzyl alcohol (0.486 g, 3.18 mmol) and acetic anhydride (0.421 g, 0.390 mL, 4.13 mmol) in CH3CN (5 mL) was stirred at room temperature as Fe(OTs)3·6H2O (43.1 mg, 0.0636 mmol, 2.0 mol %) was added. The progress of the reaction was followed by gas chromatography. After 45 min, CH3CN was removed on a rotary evaporator, and then aqueous 10% Na2CO3 (5 mL) was added to the residue and stirred for 10 min. The reaction mixture was extracted with ethyl acetate (2 × 20 mL). The combined organic layers were washed with saturated NaCl (15 mL), dried (Na2SO4) and concentrated on a rotary evaporator to yield 0.61 g (98%) of a yellow solid that was identified as p-nitrobenzyl acetate and was determined to be 97% pure by GC, 1H NMR, and 13C spectroscopy. |
93% | With silica-sulfuric acid nanoparticles In neat (no solvent) at 20℃; for 0.25h; | |
92% | With magnesium bis(trifluoromethane solfonyl)imide at 20℃; for 0.5h; | |
92% | With C7H10N2*C8HF15O2 at 25℃; for 17h; neat (no solvent); | |
91% | Stage #1: acetic anhydride With dimethyl-N-(1-trimethylsilyloxy-1-methylmethylidene)ammonium trifluoromethanesulfonate In dichloromethane at 20℃; for 0.5h; Stage #2: (-)-menthol In dichloromethane at 20℃; for 0.5h; | |
91% | With 4-imidazol-1-ylbutane-1-sulfonic acid at 50℃; for 0.166667h; | Typical procedure for acetylation of alcohols, phenols,amines, and thiols General procedure: In a 25-mL round bottom flask, a mixture of the substrate(2.0 mmol), acetic anhydride (4.0 mmol), and ImBuSO3H (2mL) was stirred at 50 C for an appropriate time. After completionof the reaction (monitored by TLC), the mixture wasextracted with Et2O (5 5 mL) and the supernatant etherealsolution was decanted off. The dual solvent-catalystImBuSO3H was allowed to remain in the flask and freshreagents could be added and the reaction could be run again.The combined ethereal solution were concentrated in vacuoto give the acetylated product identical (IR, 1H and 13CNMR and GC-MS) to an authentic sample. |
90% | With zirconium(IV) chloride at 20℃; for 0.5h; | |
90% | With perchloric acid at 20℃; for 0.0833333h; | |
89% | In acetonitrile at 80℃; for 2h; | |
89% | With H-Y zeolite at 60℃; for 2h; | |
89% | With manganese(II) chloride tetrahydrate In neat (no solvent) at 25℃; for 5h; | General procedure for acetylation General procedure: To a stirred mixture of alcohol/phenol/thiohenol/amine (1 mmol) and acetic anhydride(1.1 mmol), 0.01 mmol of MnCl24H2O was added at room temperature. The reaction mixture was stirred until alcohol/phenol/thiohenol/amine was consumed, the progress of the reaction was monitored by TLC. The reaction mixture was quenched with saturated aq. NaHCO3 and extracted with ethyl acetate (10mL 3). The organic layer was dried over anhydrous Na2SO4 and concentrated under reduced pressure. The crude was passed through a small pad of silica gel (eluent: hexane: ethyl acetate) to obtain pure acetates (acetamides were precipitated out/crystallized direct from the reaction mixture) and characterized by 1H NMR and IR spectroscopy. The data was found to be in accord with previously reported acetates. Characterization data and 1H NMR spectra can be found via the “SupplementaryContent” section of this article’s webpage. |
89% | With C81H157N3; triethylamine In toluene at 20℃; for 3h; | |
88% | for 1.5h; Heating; | |
88% | With rice-husk-supported FeCl3 nano particles In neat (no solvent) at 80℃; for 1.75h; | |
88% | With pyridine at 20℃; for 12h; | |
87% | In acetonitrile at 20℃; for 0.75h; | |
86% | With tetrachlorosilane In hexane at 20℃; for 0.166667h; | |
86% | With poly(N-vinylimidazole) In neat (no solvent) at 20℃; for 0.416667h; Green chemistry; | |
86% | With succinimide-N-sulfonic acid In neat (no solvent) at 20℃; for 0.25h; | 2.3. Acetylation of alcohols, phenols, thiols, and amines with different substrates General procedure: A mixture of 1 mmol substrate, 2-3 mmol acetic anhydride, and 5 mg SuSA (0.028 mmol) was stirred at room temperature in the absence of a solvent. The progress of the reaction was monitored by TLC. After completion of the reaction, the mixture was diluted with 15 ml ethyl acetate and filtered. Then the solid residue was washed with 5 ml ethyl acetate, then 5 ml acetone and then dried. The recovered catalyst could be used for three more reaction runs. The organic layer was washed with 5 ml of a saturated solution of NaHCO3, 20 ml brine and 20 ml water, and dried over MgSO4. Evaporation of the solvent followed by column chromatography on silica gel followed by evaporation of the solvent gave the desired product in good to high yields. |
84% | at 20℃; for 9h; | |
83% | at 20℃; for 6h; | |
82% | In acetonitrile at 20℃; for 2h; | |
82% | With ruthenium(III) 2,4-pentanedionate at 25℃; for 6.5h; | |
80% | at 50℃; for 2h; | |
74% | With pyridine; dmap at 20℃; for 1h; | |
54% | With potassium tropolonato In acetonitrile at 70℃; for 4h; | |
With 4-pyrrolidin-1-ylpyridine; triethylamine In dichloromethane other reagents; relative rates; | ||
98 % Chromat. | With K5<CoW12O40> at 20℃; for 0.116667h; | |
98 % Chromat. | In water at 225℃; for 0.00275h; | |
at 20℃; for 0.1h; | ||
With pyridine at 20℃; for 12h; | ||
With magnesium bromide at 50℃; for 3h; | 68-76 Preparation of a stock solution of menthol and methacrylic anhydride 37.8 g (0.17 mol) of natural menthol and 161.9 g (0.1785 mol) of acetic acid anhydride were combined. The obtained mixture was gently heated in the absence of any catalyst and a clear stock solution was obtained. General Procedure for Examples 68-76 7 g samples of the stock solution were placed in a 15 mL pressure tube with a Teflon plug and a magnetic agitator. To this solution, 0.1 mol% (unless indicated otherwise), based on the menthol, of the first catalyst were added and the pressure tube was tightly closed. Subsequently, the pressure tubes were placed for 3 h in an oil bath at 50 °C (unless indicated otherwise) with an integrated magnetic stirrer and stirredAfter 3 hours, the contents of acetic acid, acetic acid anhydride, menthol and of the product were determined by gas chromatography (area-%). Based on these data, the reaction conversion, based on the acetic acid anhydride and on the menthol was calculated.The results of Examples 68-76 are summarised in Table 2 below: | |
99 %Spectr. | With sulfonated biochar at 20.1℃; for 4h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
69% | In toluene at 110℃; for 8h; | |
69% | With zeolite Hβ In toluene for 8h; Heating; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With methanesulfonic acid at 30 - 35℃; for 2h; | |
98% | With copper(II) nitrate for 3.5h; Heating; | |
98% | at 116℃; for 10h; |
98% | With bismuth(lll) trifluoromethanesulfonate at 20℃; for 0.5h; | |
98.3% | at 131.84℃; for 6h; Green chemistry; | |
97% | With perchloric acid; silica gel at 80℃; for 6h; | |
96% | Stage #1: acetic acid With magnesium(II) chloride hexahydrate In ethyl acetate for 0.333333h; Green chemistry; Stage #2: (-)-menthol With sulfuric acid; sodium sulfate In ethyl acetate at 76℃; for 18h; Green chemistry; | 2 [Example 2] Preparation of Menthyl acetate 1. Add 300 mL of EA and 8 mL of AcOH to a 1000 mL round-bottom flask, dissolve and then add 72 g of MgCl2-6H2O.2. After stirring for 20 minutes, add 20 g of Menthol (unrefined raw material extracted from natural substances) and 497 g of Na2SO4, and then slowly add 433 mL of H2SO.3. Keep the temperature at 76°C and stir for 18 hours.4. The reaction mixture is cooled to room temperature, filtered, and then concentrated.5. Add 100 mL of EA to dissolve, and then wash the organic layer with saturated NaHCO 3 aqueous solution once.6. Remove water with Na2SO4, filter and concentrate to obtain a yellow oil of Menthyl acetate (17g, 96%). |
95% | at 65℃; for 24h; | |
95% | With potassium fluoride at 80℃; for 7h; | |
92% | With cerium(IV) trifluoromethanesulfonate for 1.5h; Heating; | |
91% | With cobalt(II) chloride at 60℃; for 23h; | |
90% | With iron(III) chloride at 20℃; for 3h; | |
85% | With sulfonic acid-functionalized periodic mesoporous organosilicas with ethyl bridging group at 60℃; for 24h; | |
80% | With zirconium hydrogen sulfate In hexane at 20℃; for 3h; | |
78% | With iodine at 85℃; for 7h; | |
70% | With K5<CoW12O40> for 4h; Heating; | |
68% | With 1H,4H-piperazine-N,N'-diium hydrogensulfate at 80℃; for 4h; | |
67% | With pyridine; diethyl chlorophosphate at 70℃; for 3h; Inert atmosphere; Neat (no solvent); | 4.2.1. General procedure for ester syntheses Table 2 (a) Typical procedure for the synthesis of l-menthol-4-chloro cinnamate, 8d: to a mixture of 4-chlorocinnamic acid (0.365 g, 2.00 mmol) and l-menthol (0.312 g, 2.00 mmol) in pyridine (3.0 mL) was added diethyl chlorophosphate (0.320 mL, 2.10 mmol) slowly at rt in an atmosphere of argon, and the reaction mixture was stirred at rt for about 30 min. The heterogenous mixture was heated at 70 °C under argon atmosphere for 3 h, during which the reaction mixture became homogeneous. Pyridine was removed in vacuo, and the residue partitioned between ethyl acetate (15.0 mL) and saturated sodium bicarbonate (5.0 mL). After stirring well (10 min), the organic layer was separated, dried over anhyd Na2SO4 and the solvent evaporated in vacuo to yield the crude product. In all cases, crude products were >95% pure by 1H NMR. Purification of 8d over silica-gel (5% ethyl acetate in hexane) afforded 0.552 g, 86% yield of pure product 8d. |
With molecular sieve at 120℃; for 8h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With lanthanum (III) nitrate * water; 1,1,1-trioctyl-1-methylphosphonium methylcarbonate for 1h; Molecular sieve; Reflux; | |
92% | for 12h; Heating; | |
89% | With iodine for 4h; Reflux; chemoselective reaction; | 2. Typical procedure for alcohol acetylation General procedure: To a solution of benzyl alcohol (0.108 g, 1 mmol) in ethyl acetate (2 mL), iodine (0.1 mmol)was added and the mixture was heated at reflux for 2 h. When the reaction was complete(monitored by TLC), it was cooled and a saturated sodium thiosulfate solution (5 mL) was added. The reaction mixture was extracted with ethyl acetate (3x10 mL). The combined organiclayers were washed with brine, dried over anhydrous sodium sulphate and concentrated invacuo. The crude was then purified by column chromatography to give 1a in 97% yield (145mg, 0.97 mmol). |
88% | With cerium(IV) trifluoromethanesulfonate for 3h; Heating; | |
83% | With 8Na(1+)*12C4H10NO(1-)*2HO(1-)*2Nd(3+) In hexane at 60℃; for 16h; Molecular sieve; Inert atmosphere; Schlenk technique; | |
35% | With K5<CoW12O40> for 8h; Heating; | |
26% | at 65 - 70℃; for 2h; | |
4.5% | With carbon tetrabromide; triphenylphosphine Ambient temperature; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | With methanol; at 20℃; for 3.5h; | 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. |
84% | With chloral hydrate; In hexane; at 0 - 5℃; for 6.0h;Inert atmosphere; | General procedure: To a stirred solution of the THP ether (4, 2.6 mmol) in sodium-dried hexane (5 ml) under nitrogen at 0-5 C was added 1 (0.65 g, 3.9 mmol). The mixture was stirred for 0.5 h and treated with water. The reaction mixture was extracted with dichloromethane (10 ml), and the organic layer was washed with brine solution,dried (Na2SO4), and concentrated in vacuo. The resulting residue was purified by column chromatography on neutral alumina (50-325 mesh, eluent: 10:90 ethyl acetate-hexane). The purity of the resulting product (5) was estimated to be >98%by 1H and 13C NMR spectroscopic analysis. |
With cerium (IV) sulfate tetrahydrate; In methanol; at 130℃; for 0.333333h;Microwave irradiation; | General procedure: A 10-mL reaction vessel was charged with a magnetic stir bar, 0.4 mmol of THP ether and 20 mol % Ce(SO4)24H2O in 2mL of MeOH. A septum cap was affixed; the vessel was placed in the microwave cavity of an Anton-Paar microwave equipment. The stirring reaction mixture was irradiated at 130 C for 20 min. After cooling to room temperature, TLC indicated the disappearance of starting material. The solid cerium sulfate was filtered off and the solvent was removed under reduced pressure. Column chromatography afforded pure alcohol. All products were spectrally identical with authentic alcohols. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | With copper(ll) sulfate pentahydrate; In methanol; at 100℃; for 0.25h;Microwave irradiation; | General procedure: A 10 mL reaction vessel was charged with amagnetic stir bar, 0.4 mmol of TBDMS ether, and 20 mol % CuSO45H2O in 2mLof MeOH. A septum cap was affixed; the vessel was placed in the microwavecavity of an Anton-Paar microwave equipment. The stirring reaction mixturewas irradiated at 100 C for 15 min. After cooling to room temperature, TLCindicated the disappearance of starting material. The solid cupric sulfate wasfiltered off and the solvent was removed under reduced pressure. Columnchromatography afforded the pure alcohol. All products were spectrallyidentical with authentic alcohols. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With methanol; 1,3-disulfonic acid imidazolium hydrogen sulfate; at 20℃; for 0.08333330000000001h;Green chemistry; | 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. |
94% | With poly (ethylene glycol)-sulfonated sodium montmorillonite nanocomposite; In methanol; at 20℃; for 0.333333h; | 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. |
88% | With Nanoporous Na+-Montmorillonite Perchloric Acid; In ethanol; at 20℃; for 0.5h; | 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. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With poly (ethylene glycol)-sulfonated sodium montmorillonite nanocomposite; In acetonitrile; at 20℃; for 0.416667h; | General procedure: HMDS (0.5 mmol) was added to a stirring mixture of the substrate(1 mmol), and the PEG-SANM nanocomposite (8 mg)in CH3CN (2 mL) at room temperature. The progress of thereaction was monitored by TLC. After completion of the reaction,the mixture was filtered and the recovered catalyst waswashed with acetonitrile and acetone, dried at 80C and reusedfor the same reaction. Evaporation of the solvent gave almostpure product. Further purification proceeded by recrystallizationto yield pure silyl ether. |
92% | With 1,3-disulfonic acid imidazolium hydrogen sulfate; In neat (no solvent); at 20℃; for 0.0666667h;Green chemistry; | General procedure: Ionic liquid [Dsim]HSO4 (6.5 mg, ?0.02 mmol) was added to a stirred mixture of alcohol, phenol or naphthol (1.0 mmol) and HMDS (80 mg, 0.5 mmol) at room temperature under solvent free conditions. After completion of the reaction (monitored by TLC, It should be noted that when addition of HMDS is finished stirring of the mixture is stopped after 1 min. TLC showed that in most of the cases the reaction is completed immediately after the addition of HMDS), the product was extracted with Et2O and the ionic liquid was recovered and was dried at 65 ?C under vacuum to remove moisture, and then reused. Evaporation of the solvent under reduced pressure gave the highly pure product without further purification. The desired pure products were characterized by comparison of their IR, NMR and MS data as well as boiling poin twith those of known compounds |
90% | With Nanoporous Na+-Montmorillonite Perchloric Acid; In acetonitrile; at 20℃; for 0.5h; | General procedure: To a stirring mixture of the substrate (1 mmol) and MMTHClO4(7 mg) in CH3CN (3 mL), HMDS (0.75 mmol)was added at room temperature. After completion of thereaction, indicated by TLC, ethyl acetate: n-hexane (3:7),the mixture was filtered to separate the catalyst. The filtratewas washed with acetonitrile (5 mL). Removal of the solvent under reduced pressure gave almost pure productin good to high yields. Further purification was carriedout by column chromatography on silica gel (eluting withEtOAc:hexane = 1:4), if necessary. |
81% | With rice husk ash; In acetonitrile; at 20℃; for 0.5h;Green chemistry; | General procedure: To a stirring mixture of the substrate (1 mmol) and RiHA (0.08 g) in CH3CN (3 mL),HMDS (0.75 mmol, 0.120 g) was added at room temperature. The progress of the reaction was monitored by TLC. After completion of the reaction, the mixture was filtered and the residue was washed with acetonitrile (5 mL). Evaporation of the solvent gave almost pure product(s). Further purification was carried out by bulb-to-bulb distillation under reduced pressure or recrystallization to afford pure silyl ether(s). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | With aluminum oxide at 25℃; for 0.166667h; | |
89% | With ZnAl2O4 nanoparticles at 20℃; for 0.5h; Neat (no solvent); | |
86% | With zinc(II) oxide at 20℃; for 0.333333h; |
83% | With Fe/SWCNTs at 20℃; for 0.333333h; | |
82% | Stage #1: (-)-menthol With sodium hydride In tetrahydrofuran at 0℃; for 1h; Stage #2: acetyl chloride In tetrahydrofuran at 0℃; for 5.5h; | |
58.5% | With pyridine In tetrahydrofuran Reflux; | |
With pyridine In chloroform at 25℃; for 1h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 39% 2: 88 % ee | With Candida cylindracea lipase; quinidine In tert-butyl methyl ether at 20℃; for 48h; Resolution of racemate; Enzymatic reaction; | Enzymatic acylation with enol esters To 1 mmol of racemic alcohol (1), 3 mmol of the appropriate enol ester (isopropenyl acetate or vinyl acetate) and a catalytic amount of lipase were dissolved in 2 mL of organic solvent. The suspension was stirred at room temperature for the indicated time. The reaction mixture was filtered on Celite and concentrated in vacuum. The remaining alcohol and the produced acetate were separated by chromatography on silica gel (petroleum ether/ethyl acetate: 95/5) and analyzed by chiral GC. The same procedure was followed for the reactions in the presence of 30 mol% of additives. |
With Pseudomonas cepacia lipase In various solvent(s) at 20℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | With hydrogenchloride In 1,4-dioxane; chloroform at 20℃; for 4h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | With poly(4-vinylpyridine) supported copper(II) oxide nanoparticles; In neat (no solvent); at 20℃; for 0.08333330000000001h; | General procedure: A mixture of the substrate (1 mmol), dimethoxymethane(DMM) (4 mmol) and PC-NPs (12 mg) was stirred at room temperature for the appropriate time. The progress of the reaction was monitored by TLC (EtOAc: n-hexane; 1:1). After completion of the reaction, the mixture was filtered,and the solid residue was washed with Et2O (5 mL). The filtrate was washed with a saturated solution of NaHCO3 and H2O and dried over MgSO4. Evaporation of the solvent afforded the requested methoxymethyl (MOM) ether in high purity. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With thionyl chloride In pyridine; Petroleum ether; benzene | 6 EXAMPLE 6 EXAMPLE 6 Preparation of (-) menthyl 4-n-decyloxybiphenyl -4'-carboxylate. 4-n-Decyloxybiphenyl-4'-carboxylic acid (2 g; 0.0056 m), which had been prepared by hydrolysis of 4-cyano-4'-n-decyloxybiphenyl (supplied by BDH, Poole, Dorset), was heated under reflux for 3 hours with thionyl chloride (30 ml). The thionyl chloride was then removed on a rotary evaporator; residual thionyl chloride was next evaporated off by azeotropic distillation using dry benzene. The acid chloride was dissolved in dry pyridine (30 ml) and cooled in an ice bath. (-)Menthol (0.94 g; 0.006 m) [[α]D16 =-44°] was dissolved in the minimum volume of dry pyridine and added to the acid chloride solution over a period of 15 minutes. The reagents were stirred for 1 hour in the ice bath, then overnight at room temperature, and finally for 2 hours at 60° C. After cooling, the mixture was poured into dilute hydrochloric (100 ml), and the product extracted with dichloromethane (100 ml). The dichloromethane layer was washed with dilute hydrochloric acid solution (100 ml) a further five times, and then with water (100 ml) and finally with a dilute solution of sodim bicarbonate (100 ml). After drying the dichloromethane solution with magnesium sulphate, it was rotary evaporated to leave a low melting point solid. This was purified by column chromatography on silica gel (70-130 mesh) using 1 part dichloromethane to 2 parts petroleum ether (b.p. 40°-60° C.) as eluent. The isolated solid was crystallized from I.M.S. to constant melting point and single spot purity by thin layer chromoatography. The melting point of the final product was 26° C., and evidence that it was indeed an ester was provided by the presence of an infra-red absorption peak at 1710 cm-1 corresponding to the C=O stretching vibration frequency. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With hydrogenchloride; sodium; chloroacetic acid In water; toluene | 1 Preparation of d-Isomenthoxyacetic Acid EXAMPLE 1 Preparation of d-Isomenthoxyacetic Acid To a 5 l. flask equipped with a mechanical stirrer, condenser, and addition funnel was added dry toluene (1 l.), d-isomenthol (2.56 moles), and sodium metal (2.6 gram-atoms). The reaction mixture was refluxed with stirring under nitrogen until all the sodium was reacted. Chloroacetic acid (1.0 moles) in toluene then was added slowly to the cooled reaction mixture. The reaction was exothermic and after the addition was complete, the reaction was refluxed for 48 hours. To the cooled solution was carefully added water (1 l.) and the organic layer was washed with two further portions of water. Separation of the toluene allowed the recovery of d-isomenthol which can be recycled. Acidification of the aqueous layer with HCl followed by extraction with diethyl ether (or methylene chloride) and evaporation of the dried organic extracts gave crude d-isomenthoxyacetic acid (0.58 moles) which can be further purified by distillation. b.p.=127°-130°/0.5 mm; [α]D =+23.85°(C=20.8)EtOH. Found: C, 67.47; H, 10.34; Calc. for C12 H22 O 3; C, 67.25; H, 10.35%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
64% | With 4 A molecular sieve In hexane at 80℃; for 24h; | |
17% | With Rasta resin-(1,5,7-triazabicyclo[4.4.0]dec-5-ene)[RR-TBD] In tetrahydrofuran at 20 - 60℃; | General Procedure for the Reaction of Various Alcoholswith Vinyl Acetate General procedure: Alcohol 24 (1.0 mmol), vinyl acetate (25) (0.103 g, 1.20mmol), 1 (0.080 g, 0.10 mmol), and THF(1.0 mL) were added to a 3-mL vial. The vial was immersed in an oil bath regulated at 60 °C for 16 h.The reaction mixture was cooled to rt and then filtered. The beads collected on funnel were furtherwashed with THF (5 mL). Combined filtrate was concentrated under reduced pressure. The residue ofconcentrated filtrate afforded essentially pure products as analyzed by 1H and 13C NMR spectroscopy forsubstrates in Table 1, entries 1-4. In cases the reactions were incomplete under the given conditions, theproducts were purified using silica gel column chromatography with hexane as the eluent. |
With lipoprotein lipase from Chromobacterium viscosum In toluene at 30℃; Enzymatic reaction; |
57 %Chromat. | With steapsin lipase In hexane at 55℃; for 72h; Enzymatic reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
on heating;; | ||
In not given | ||
In not given |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
25% | Stage #1: (-)-menthol; Dichlorophenylphosphine With pyridine In hexane at 0℃; for 12h; Inert atmosphere; Stage #2: With water In hexane at 0℃; Inert atmosphere; | |
With pyridine; water In diethyl ether at 0 - 20℃; Inert atmosphere; | ||
Stage #1: (-)-menthol; Dichlorophenylphosphine With pyridine In diethyl ether at 0 - 23℃; Stage #2: With water In diethyl ether Overall yield = 58 %; Overall yield = 5.2 g; Optical yield = 23.077 %de; |
66 % de | Stage #1: (-)-menthol; Dichlorophenylphosphine With pyridine In diethyl ether at 20℃; for 4.5h; Cooling with ice; Inert atmosphere; Stage #2: With water In diethyl ether at -80℃; for 4h; Inert atmosphere; | |
Stage #1: (-)-menthol; Dichlorophenylphosphine With pyridine In diethyl ether at 0 - 20℃; Inert atmosphere; Schlenk technique; Stage #2: With water In diethyl ether at -78 - 20℃; for 6h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80.8% | With triethylamine In dichloromethane; chloroform at -10℃; for 6h; | |
With triethylamine In chloroform at -10℃; for 6h; | General procedure for synthesis of S-(+)-ibuprofenspacer-antioxidant hybrids General procedure: In a 250ml two neck flask, a mixture of antioxidant[thymol (2), guaiacol (3), eugenol (4) and menthol (5)(0.01mol)], TEA (1.01g, 1.4ml, 0.01mol) in CHCl3 (25ml)was cooled in an ice salt mixture to -10°C. To this reactionmixture, chloroacetyl chloride (1.12g, 0.8ml, 0.01mol) inCHCl3 (25ml) was added drop wise with constant stirringover a period of 1h, maintaining the temperature constant.The reaction mixture was stirred further 5h, washed withHCl (5%, 3x50ml) sodium hydroxide (5%, 3x50ml) and finallywith brine solution (2x25ml). The organic layer wasdried over anhydrous sodium sulphate, filtered and the solventwas removed under reduced pressure to obtain antioxidantchloroacetate (2a, 3a, 4a and 5a). In a 250ml two neckflask, a mixture of antioxidant chloroacetate (2a, 3a, 4a and5a) (0.01mol), ibuprofen (1) (2.06g, 0.01mol), TEA (1.01g,1.4ml, 0.01mol) and sodium iodide (1.5g, 0.01mol) in DMF(25ml) was heated at 80-90°C for 6h, with constant stirring.The reaction mixture was cooled under tap water, pouredinto finely crushed ice with stirring and extracted with ethylacetate (4x25ml). The combined organic layer was washedwith sodium thiosulphate (2%, 3x50ml), HCl (5%, 3x50ml),sodium hydroxide (5%, 3x50ml) and finally with brine solution(2x25ml). The organic layer was dried over anhydroussodium sulphate, filtered and the solvent was removed underreduced pressure to obtain semisolid residue, which waschromatographed on silica gel column using CHCl3 : ethylacetate (9.5 : 0.5) mixture as eluent. The fractions were combinedand the solvent was removed under reduced pressureto yield respective S-(+)-ibuprofen-spacer-antioxidant hybrids(10-13). | |
With triethylamine In chloroform at -10 - 20℃; for 8h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
46% | Stage #1: (-)-menthol; Dichlorophenylphosphine With pyridine In diethyl ether at 0 - 20℃; Inert atmosphere; Stage #2: With water In diethyl ether Inert atmosphere; | |
23% | With pyridine In diethyl ether at 0 - 20℃; Inert atmosphere; | |
19% | Stage #1: (-)-menthol; Dichlorophenylphosphine With pyridine In hexane at 0 - 20℃; for 12h; Stage #2: With water In hexane for 0.5h; diastereoselective reaction; |
Stage #1: (-)-menthol; Dichlorophenylphosphine With pyridine at 0℃; Inert atmosphere; Stage #2: With water Inert atmosphere; | ||
Stage #1: (-)-menthol; Dichlorophenylphosphine With pyridine at 0℃; Inert atmosphere; Stage #2: With water | ||
With pyridine In diethyl ether at 0℃; | 1-9 Example 1 At room temperature, 5 mmol of dichlorophenylphosphine was added to 40 ml of ether, and 80 ml of a solution of 5 mmol of menthol and 5 mmol of pyridine was slowly added dropwise at 0 ° C overnight; recrystallization at -30 ° C gave the chiral phosphonate.Extract 11 mmol from the methylmagnesium bromide reagent bottle, and slowly add dropwise to -80 ° C into a solution of 5 mmol phosphonate in ether, overnight; after the reaction is completed, add saturated ammonium chloride solution, extract and spin through the column to obtain an oily product ;The product was dissolved in tetrahydrofuran, and equimolar sodium bis(trimethylsilyl)amide was slowly added dropwise at room temperature overnight. After the reaction was completed, the product was washed with petroleum ether. Final product: white powder, yield: 93%, ee value: 97%. | |
With pyridine In tetrahydrofuran at 0 - 20℃; Inert atmosphere; | ||
Stage #1: (-)-menthol; Dichlorophenylphosphine With triethylamine In diethyl ether at -50℃; Schlenk technique; Stage #2: With water In diethyl ether at -50℃; Schlenk technique; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With Pseudomonas fluorescens lipase (Amano AK) In n-heptane at 40℃; Enzymatic reaction; optical yield given as %ee; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With lipoprotein lipase from Pseudomonas cepacia In n-heptane at 40℃; for 24h; Enzymatic reaction; optical yield given as %ee; enantioselective reaction; | ||
With nano-SnO2-immobilized Rhizopus delemar lipase In hexane at 25℃; for 20h; Resolution of racemate; Ionic liquid; | 2.8 Kinetic resolution of menthol General procedure: In a typical experiment, 4mmol of (±)-menthol and 5U biocatalyst were added to 1mL hexane in a screw-capped vial. The reaction was initiated by adding 4mmol acylating reagent (vinyl acetate). The reaction mixture was magnetically stirred (200rpm) at 25°C for 20h. The initial water activity of the reaction mixture was maintained at 0.33 by using saturated solution of magnesium chloride [36], and then maintained using molecular sieve 3. Control experiments without enzyme were performed. To determine the temperature effect on the efficiency and enantioselectivity of both studied biocatalysts, the reactions of acylation of (±)-menthol with vinylacetate were performed in the temperature range from 20°C to 40°C. To determine the effect of ionic liquids on the enantioselectivity of nano-SnO2-RhD and NH2-nano-SnO2-RhD, 1mmol of IL were added to the reaction mixtures. (0027) Aliquots (100μL) from the reaction mixture were withdrawn periodically, extracted with 500μL of hexane/5%NaHCO3 (1:1), and the hexane layer was analyzed by gas chromatography. The analyses were performed on a Shimadzu GC-17A instrument equipped with CycloSil-B (Agilent) column (0.25μm×0.25mm×30m) and fitted with a flame ionization detector. The column was maintained at 90°C for 10min, and then the temperature was increased first to 150°C at 3°C/min, and after that to 165°C at 5°C/min, and finally the temperature was maintained at 165°C for 5min. The temperature of the injector was 220°C and that of the detector -250°C. Nitrogen was used as a gas carrier. The retention times were 24.3min for (+)-menthol, 25.1min for (-)-menthol, 33.5min for (-)-menthyl acetate, and 34.1min for (+)-menthyl acetate. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With hydrogen In hexane at 100℃; | 2.2 Hydrogenation experiments General procedure: The supported ionic liquid catalysts were used in the hydrogenation of citral (Aldrich, 95%). Hydrogenation experiments were performed in a semi-batch reactor (Parr Instrument Company). The total volume of the reactor was 600 ml whereas the effective liquid volume was 250 ml. The temperature and stirring rate were controlled by a Parr 4843 control unit (Watlow control series 982). All experiments were performed at a constant pressure and temperature. Approximately 3 g of citral (0.02 mol) was dissolved in 250 ml of n-hexane (Merck, >99%). In the beginning of each experiment, the reactor was heated to a desired temperature and, at the same time, the hydrogen pressure was also adjusted to desired level. After the citral solution was injected to the reactor, the stirring was commenced and this was considered as the starting point for the reaction. (0006) Citral hydrogenation products were identified by means of gas chromatography (Hewlett Packard 6890 GC with FI detector). In addition, a gas chromatograph coupled to a mass-spectrometer (Agilent 6980N GC with Agilent 5973 MS detector) was used to identify the peaks of citral hydrogenation products. The peaks in the chromatogram were identified with the following reference substances: (±)-citronellal (Fluka, 80-90%), nerol (Fluka, >90%), geraniol (Alfa Aesar, 97%), (+)-neomenthol (Fluka, 98.5%), (-)-isopulegol (Aldrich, 99%), tetrahydrogeraniol (Aldrich, 99%), menthol (Aldrich, 99%), (+)-isomenthol (Fluka, >99%), and (±)-β-citronellol (90-95%, Fluka). The progress of citral hydrogenation reaction was monitored by taking samples from the reactor and analyzing them by means of gas chromatography. In the case of standard samples and samples taken from reactor, 500 μl of internal standard (0.02 M cyclohexanone in cyclohexane) was added into a 500 μl of sample. The GC column used was an Agilent DB-5 with a length of 60 m, inner diameter of 0.32 mm and a film thickness of 1 μm. The following temperature program was applied: 10 min at 100 °C, then raised 5 °C/min to 160 °C. Temperature was then held 10 min at 160 °C. At the end the temperature was increased 13 °C/min to 200 °C and kept constant for 1 min. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 88% 2: 8% | With bromine; triphenylphosphine In acetonitrile at 20℃; for 5h; | Typical procedure for the conversion of 3-phenylpropanol into 3-phenylpropyl acetate using Ph3P/Br2/NH4OAc General procedure: To a solution of Ph3P(OAc)2, was added 3-phenylpropanol (1 mmol, 0.137 mL). The progress of the reaction was monitored by TLC (Table 3, entry 2). After completion of the reaction (0.3 h) the reaction mixture was filtered to remove the precipitated NH4Br followed by evaporation of the solvent. Column chromatography of the crude mixture on silica gel using n-hexane/EtOAc (3:1) as the eluent gave 3-phenylpropyl acetate in 90% yield (0.159 g). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: pyridine / diethyl ether / 0 - 20 °C / Inert atmosphere 2: triethylamine / tetrachloromethane / 20 °C / Inert atmosphere | ||
Multi-step reaction with 2 steps 1.1: pyridine / diethyl ether / 0 - 20 °C / Inert atmosphere 1.2: Inert atmosphere 2.1: triethylamine / tetrachloromethane / 20 °C / Inert atmosphere |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: pyridine / diethyl ether / 0 - 20 °C / Inert atmosphere 2: triethylamine / tetrachloromethane / 20 °C / Inert atmosphere |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: pyridine / diethyl ether / 0 - 20 °C / Inert atmosphere 2: triethylamine / tetrachloromethane / 20 °C / Inert atmosphere | ||
Multi-step reaction with 2 steps 1.1: pyridine / diethyl ether / 0 - 20 °C / Inert atmosphere 1.2: Inert atmosphere 2.1: triethylamine / tetrachloromethane / 20 °C / Inert atmosphere |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: pyridine / diethyl ether / 0 - 20 °C / Inert atmosphere 2: triethylamine / tetrachloromethane / 20 °C / Inert atmosphere | ||
Multi-step reaction with 2 steps 1.1: pyridine / diethyl ether / 0 - 20 °C / Inert atmosphere 1.2: Inert atmosphere 2.1: triethylamine / tetrachloromethane / 20 °C / Inert atmosphere |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: pyridine / diethyl ether / 0 - 20 °C / Inert atmosphere 2: triethylamine / tetrachloromethane / 20 °C / Inert atmosphere | ||
Multi-step reaction with 2 steps 1.1: pyridine / diethyl ether / 0 - 20 °C / Inert atmosphere 1.2: Inert atmosphere 2.1: triethylamine / tetrachloromethane / 20 °C / Inert atmosphere |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1.1: phosphinic acid / water / 24 h / 75 °C 1.2: 24 h / 20 °C / Reflux; Inert atmosphere; Dean-Stark 2.1: palladium diacetate; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene; N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide; 1,2-dimethoxyethane / 24 h / 115 °C / Inert atmosphere |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With dodecacarbonyl-triangulo-triruthenium; 4,5-bis((diisopropylphosphanyl)methyl)acridine; ammonia In tert-Amyl alcohol at 170℃; for 21h; Inert atmosphere; Schlenk technique; Autoclave; | ||
With dodecacarbonyl-triangulo-triruthenium; 4,5-bis((diisopropylphosphanyl)methyl)acridine; ammonia In tert-Amyl alcohol at 150℃; for 63h; Inert atmosphere; Schlenk technique; Autoclave; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
26% | Stage #1: (-)-menthol; phenylphosphinic acid In toluene for 24h; Reflux; Inert atmosphere; Dean-Stark; Stage #2: formaldehyd In toluene for 24h; Reflux; Inert atmosphere; Dean-Stark; | (Sp)-Menthyl(hydroxymethyl)phenylphosphinate 5 To a solution of phenylphosphinic acid (42.6 g, 300 mmol, 1 equiv) in toluene (300 mL) was added L-menthol (46.9 g, 300 mmol, 1 equiv). The reaction mixture was then stirred at reflux for 24 h under N2 and in a flask equipped with a Dean-stark trap. After cooling down the reaction to rt, paraformaldehyde (9.01 g, 300 mmol, 1 equiv) was added and the reaction mixture was stirred at reflux for 24 h under N2. The solvent was then removed under vacuum and the crude obtained was recrystallized at rt in diethyl ether (200 mL) to afford the product as colorless crystals (24.2 g, 26%, de=95%). Mp=138-139° C.; 31P NMR (121.47 MHz, CDCl3): H=37.2 (s); 1H NMR (300 MHz, CDCl3): □=7.77-7.87 (m, 2H), 7.52-7.60 (m, 1H), 7.42-7.51 (m, 2H), 4.29-4.43 (m, 2H), 3.93-4.10 (m, 2H), 2.26 (dquint., J=2.6 and 7.0 Hz, 1H), 1.80-1.91 (m, 1H), 1.57-1.73 (m, 2H), 1.26-1.47 (m, 2H), 0.96 (d, J=7.1 Hz, 3H), 0.74-1.13 (m, 3H), 0.89 (d, J=7.0 Hz, 3H), 0.78 (d, J=6.4 Hz, 3H); 13C NMR (75.46 MHz, CDCl3): □□=132.3 (d, JPCCCC=2.8 Hz), 131.7 (d, JPCCC=9.9 Hz, 2C), 130.6 (d, JPC=123 Hz), 128.3 (d, JPCC=12.1 Hz, 2C), 77.1 (d, JPOC=8.3 Hz), 60.2 (d, JPC=117 Hz), 48.7 (d, JPOCC=6.1 Hz), 43.2, 34.0, 31.4, 25.5, 22.8, 21.9, 21.1, 15.7; HRMS (EI+) m/z calcd for C16H28O3P ([M+H]+) 311.1776. found 311.1766; [α]D=-46.74°. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With nano-SnO2-immobilized Rhizopus delemar lipase In hexane at 25℃; for 20h; Resolution of racemate; | 2.8 Kinetic resolution of menthol General procedure: In a typical experiment, 4mmol of (±)-menthol and 5U biocatalyst were added to 1mL hexane in a screw-capped vial. The reaction was initiated by adding 4mmol acylating reagent (vinyl acetate). The reaction mixture was magnetically stirred (200rpm) at 25°C for 20h. The initial water activity of the reaction mixture was maintained at 0.33 by using saturated solution of magnesium chloride [36], and then maintained using molecular sieve 3. Control experiments without enzyme were performed. To determine the temperature effect on the efficiency and enantioselectivity of both studied biocatalysts, the reactions of acylation of (±)-menthol with vinylacetate were performed in the temperature range from 20°C to 40°C. To determine the effect of ionic liquids on the enantioselectivity of nano-SnO2-RhD and NH2-nano-SnO2-RhD, 1mmol of IL were added to the reaction mixtures. (0027) Aliquots (100μL) from the reaction mixture were withdrawn periodically, extracted with 500μL of hexane/5%NaHCO3 (1:1), and the hexane layer was analyzed by gas chromatography. The analyses were performed on a Shimadzu GC-17A instrument equipped with CycloSil-B (Agilent) column (0.25μm×0.25mm×30m) and fitted with a flame ionization detector. The column was maintained at 90°C for 10min, and then the temperature was increased first to 150°C at 3°C/min, and after that to 165°C at 5°C/min, and finally the temperature was maintained at 165°C for 5min. The temperature of the injector was 220°C and that of the detector -250°C. Nitrogen was used as a gas carrier. The retention times were 24.3min for (+)-menthol, 25.1min for (-)-menthol, 33.5min for (-)-menthyl acetate, and 34.1min for (+)-menthyl acetate. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With nano-SnO2-immobilized Rhizopus delemar lipase In hexane at 25℃; for 20h; Resolution of racemate; | 2.8 Kinetic resolution of menthol General procedure: In a typical experiment, 4mmol of (±)-menthol and 5U biocatalyst were added to 1mL hexane in a screw-capped vial. The reaction was initiated by adding 4mmol acylating reagent (vinyl acetate). The reaction mixture was magnetically stirred (200rpm) at 25°C for 20h. The initial water activity of the reaction mixture was maintained at 0.33 by using saturated solution of magnesium chloride [36], and then maintained using molecular sieve 3. Control experiments without enzyme were performed. To determine the temperature effect on the efficiency and enantioselectivity of both studied biocatalysts, the reactions of acylation of (±)-menthol with vinylacetate were performed in the temperature range from 20°C to 40°C. To determine the effect of ionic liquids on the enantioselectivity of nano-SnO2-RhD and NH2-nano-SnO2-RhD, 1mmol of IL were added to the reaction mixtures. (0027) Aliquots (100μL) from the reaction mixture were withdrawn periodically, extracted with 500μL of hexane/5%NaHCO3 (1:1), and the hexane layer was analyzed by gas chromatography. The analyses were performed on a Shimadzu GC-17A instrument equipped with CycloSil-B (Agilent) column (0.25μm×0.25mm×30m) and fitted with a flame ionization detector. The column was maintained at 90°C for 10min, and then the temperature was increased first to 150°C at 3°C/min, and after that to 165°C at 5°C/min, and finally the temperature was maintained at 165°C for 5min. The temperature of the injector was 220°C and that of the detector -250°C. Nitrogen was used as a gas carrier. The retention times were 24.3min for (+)-menthol, 25.1min for (-)-menthol, 33.5min for (-)-menthyl acetate, and 34.1min for (+)-menthyl acetate. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With hydrogen In cyclohexane at 120℃; for 3h; | 3 Hydrogenation of Menthone to Menthol [0085] The menthone formed in Example 1 sample L3 was separated off by distillation at a bottom temperature of 133° C. and hydrogenated to menthol at 120° C. and 30 bar. The catalyst used was 5% Ru/Alox reduced from Alfa Aesar. The reaction was carried out in the solvent cyclohexane. [0086] Menthone had reacted completely after a good 3 h. Neomenthol and menthol were formed in approximately equal fraction. The fraction of the undesired products iso- and neoisomenthol is negligibly small. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1.1: pyridine / diethyl ether / 0 - 20 °C / Inert atmosphere 1.2: Inert atmosphere 2.1: triethylamine / tetrachloromethane / 20 °C / Inert atmosphere 3.1: diisopropylamine; n-butyllithium / tetrahydrofuran / 1 h / -78 °C / Inert atmosphere |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1.1: pyridine / diethyl ether / 0 - 20 °C / Inert atmosphere 1.2: Inert atmosphere 2.1: triethylamine / tetrachloromethane / 20 °C / Inert atmosphere 3.1: diisopropylamine; n-butyllithium / tetrahydrofuran / 1 h / -78 °C / Inert atmosphere |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1.1: pyridine / diethyl ether / 0 - 20 °C / Inert atmosphere 1.2: Inert atmosphere 2.1: triethylamine / tetrachloromethane / 20 °C / Inert atmosphere 3.1: diisopropylamine; n-butyllithium / tetrahydrofuran / 1 h / -78 °C / Inert atmosphere |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1.1: pyridine / diethyl ether / 0 - 20 °C / Inert atmosphere 1.2: Inert atmosphere 2.1: triethylamine / tetrachloromethane / 20 °C / Inert atmosphere 3.1: diisopropylamine; n-butyllithium / tetrahydrofuran / 1 h / -78 °C / Inert atmosphere |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1.1: pyridine / diethyl ether / 0 - 20 °C / Inert atmosphere 1.2: Inert atmosphere 2.1: triethylamine / tetrachloromethane / 20 °C / Inert atmosphere 3.1: diisopropylamine; n-butyllithium / tetrahydrofuran / 1 h / -78 °C / Inert atmosphere |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1.1: pyridine / diethyl ether / 0 - 20 °C / Inert atmosphere 1.2: Inert atmosphere 2.1: triethylamine / tetrachloromethane / 20 °C / Inert atmosphere 3.1: diisopropylamine; n-butyllithium / tetrahydrofuran / 1 h / -78 °C / Inert atmosphere |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1.1: pyridine / diethyl ether / 0 - 20 °C / Inert atmosphere 1.2: Inert atmosphere 2.1: triethylamine / tetrachloromethane / 20 °C / Inert atmosphere 3.1: diisopropylamine; n-butyllithium / tetrahydrofuran / 1 h / -78 °C / Inert atmosphere |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1.1: pyridine / diethyl ether / 0 - 20 °C / Inert atmosphere 1.2: Inert atmosphere 2.1: triethylamine / tetrachloromethane / 20 °C / Inert atmosphere 3.1: diisopropylamine; n-butyllithium / tetrahydrofuran / 1 h / -78 °C / Inert atmosphere |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1.1: pyridine / diethyl ether / 0 - 20 °C / Inert atmosphere 1.2: Inert atmosphere 2.1: triethylamine / tetrachloromethane / 20 °C / Inert atmosphere 3.1: diisopropylamine; n-butyllithium / tetrahydrofuran / 1 h / -78 °C / Inert atmosphere |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1.1: pyridine / diethyl ether / 0 - 20 °C / Inert atmosphere 1.2: Inert atmosphere 2.1: triethylamine / tetrachloromethane / 20 °C / Inert atmosphere 3.1: diisopropylamine; n-butyllithium / tetrahydrofuran / 1 h / -78 °C / Inert atmosphere |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1.1: pyridine / diethyl ether / 0 - 20 °C / Inert atmosphere 1.2: Inert atmosphere 2.1: triethylamine / tetrachloromethane / 20 °C / Inert atmosphere 3.1: diisopropylamine; n-butyllithium / tetrahydrofuran / 1 h / -78 °C / Inert atmosphere |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1.1: pyridine / diethyl ether / 0 - 20 °C / Inert atmosphere 1.2: Inert atmosphere 2.1: triethylamine / tetrachloromethane / 20 °C / Inert atmosphere 3.1: diisopropylamine; n-butyllithium / tetrahydrofuran / 1 h / -78 °C / Inert atmosphere |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | Stage #1: (-)-menthol With sodium hydride In tetrahydrofuran at 20℃; for 0.5h; Inert atmosphere; Stage #2: (4S,4'S)-2,2'-bis(o-fluorophenyl)-4,4',5,5'-tetrahydro-4,4'-bi(1,3-oxazole) In tetrahydrofuran Reflux; | Synthesis of (4S,4'S)-2-(2-((1R,2S,5R)-2-isopropyl-5-methylcyclohexyloxy) phenyl)-2'-(2-((1S,2R,5S)-2-isopropyl-5-methylcyclohexyloxy)phenyl)-4,4',5,5'-tetrahydro-4,4'-bioxazoleL5 500mg (12 mmol) of 60% NaH (in Paraffin wax) was charged with flame dried two neck roundbottom flask and the paraffin was removed by dry hexane wash then 20 mL of dry THF wasadded followed by the solution of 1.42g (9 mmol) of (L)-menthol (in 5 mL THF) was added dropwise. The resulting mixture was stirred an additional 30min under argon atm at ambienttemperature then the dissolution of 2,2'-bis(2-fluorophenyl)-4,4',5,5'-tetrahydro-4,4'-bioxazole (1g (3 mmol) in 5 mL dry THF)was added to the stirred solution of reaction mixture. The finalreaction mixture was refluxed overnight; after completion ofreaction it was quenched by crushed ice and taken extract withethyl acetate twice. The organic fractions were combined, driedover anhydrous Na2SO4 and the filtered solution was concentratedthrough rotary evaporator. The resulting crude bi(oxazoline) L5 was subsequently purified byflash column chromatography using 100-200 mesh silica gel with 30:70 ethylacetate:hexaneelution. 16g (2.67 mmol, 88% yield) of the purified ligand L5 was isolated as white solid. M.p.142-146 °C, 1H NMR (500 MHz, CDCl3): δ 7.64 (dd, J = 6.5, 1.5 Hz, 1H), 7.38 (td, J = 7, 2 Hz,1H), 6.98 (d, J = 8.5 Hz, 1H), 6.92 (t, J = 7.5 Hz, 1H), 4.89-4.85 (m, 1H), 4.38-4.30 (m, 2H),4.15-4.10 (m, 1H), 2.33-2.28 (m, 1H), 2.21-2.18 (m, 1H), 1.76-1.36 (m, 2H), 1.62-1.58 (m, 1H),1.50-1.47 (m, 1H), 1.17-1.08 (m, 2H), 0.95-0.93 (m, 6H), 0.75 (d, J = 7.5 Hz, 3H). 13C NMR(125 MHz, CDCl3): 165.2, 157.2, 131.9, 131.2, 119.7, 118.4, 113.4, 78.2, 68.7, 68.1, 48.0, 40.1,34.4, 31.4, 25.7, 23.5, 22.1, 20.8, 16.4. IR (ν, cm-1): 3127, 3105, 3030, 2980, 1648, 1635, 1530,1374, 1283, 1210, 1124, 1031, 839, 858, 784; HRMS (ESI) C38H53N2O4 [M+H]+ calc for601.4000, found 601.4007. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
40% | With triphenylphosphine In chloroform for 12h; Reflux; Inert atmosphere; | General Procedure B: Synthesis of acetates 12 General procedure: Into a conical flask was added the alcohol (1 eq), DCM or CHCl3 (0.5 mL) and triphenylphosphine (1.1 eq).To this was added (diacetoxyiodo)benzene 5 (1.1 eq) and the reaction mixture was stirred at either roomtemperature or reflux. The crude reaction mixtures were concentrated by rotary evaporation and purified bycolumn chromatography. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With hafnium tetrakis(trifluoromethanesulfonate) In neat (no solvent) at 150℃; for 3h; Overall yield = 82 %; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 32% 2: 66 % ee | With Candida cylindracea lipase In diethyl ether at 20℃; for 48h; Resolution of racemate; Enzymatic reaction; | Enzymatic acylation with enol esters To 1 mmol of racemic alcohol (1), 3 mmol of the appropriate enol ester (isopropenyl acetate or vinyl acetate) and a catalytic amount of lipase were dissolved in 2 mL of organic solvent. The suspension was stirred at room temperature for the indicated time. The reaction mixture was filtered on Celite and concentrated in vacuum. The remaining alcohol and the produced acetate were separated by chromatography on silica gel (petroleum ether/ethyl acetate: 95/5) and analyzed by chiral GC. The same procedure was followed for the reactions in the presence of 30 mol% of additives. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 9 % ee 2: 27 % ee | With Candida cylindracea lipase; quinidine In n-heptane at 20℃; for 48h; Resolution of racemate; Enzymatic reaction; | Enzymatic acylation with enol esters To 1 mmol of racemic alcohol (1), 3 mmol of the appropriate enol ester (isopropenyl acetate or vinyl acetate) and a catalytic amount of lipase were dissolved in 2 mL of organic solvent. The suspension was stirred at room temperature for the indicated time. The reaction mixture was filtered on Celite and concentrated in vacuum. The remaining alcohol and the produced acetate were separated by chromatography on silica gel (petroleum ether/ethyl acetate: 95/5) and analyzed by chiral GC. The same procedure was followed for the reactions in the presence of 30 mol% of additives. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 75 % ee 2: 42% | With Candida cylindracea lipase; quinidine In diethyl ether at 20℃; for 48h; Resolution of racemate; Enzymatic reaction; | Enzymatic acylation with enol esters To 1 mmol of racemic alcohol (1), 3 mmol of the appropriate enol ester (isopropenyl acetate or vinyl acetate) and a catalytic amount of lipase were dissolved in 2 mL of organic solvent. The suspension was stirred at room temperature for the indicated time. The reaction mixture was filtered on Celite and concentrated in vacuum. The remaining alcohol and the produced acetate were separated by chromatography on silica gel (petroleum ether/ethyl acetate: 95/5) and analyzed by chiral GC. The same procedure was followed for the reactions in the presence of 30 mol% of additives. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With dmap In toluene at 125℃; | 5.1; 5.2; 5.3 (1)Batching process: using menthol and glutaric anhydride as raw materials,Using toluene as a solvent and DMAP as a catalyst,Weigh 85g of glutaric anhydride, add 1.5L of toluene, add 250g of menthol,The catalyst DMAP is 20g, menthol, glutaric anhydride,Toluene and DMAP are mixed in a reaction vessel to form a reactant system mixture;(2)The menthol esterification reaction is carried out in a reaction vessel, and the reaction temperature of the reactant system mixture in the step (1) is controlled to be 125 ° C above the boiling point of the solvent.Heating and refluxing with water, the reaction time is 10h;The menthol esterification reaction of the present embodiment is carried out in a solution;(3)After the end of the esterification reaction, the precipitate is removed by filtration.The filtrate is washed twice with a 10% by mass Na2CO3 solution and a saturated brine, and then the washed organic layer product is dried with anhydrous Na2SO4 to obtain a crude product by concentration; then the crude product is subjected to column chromatography. Separate,Obtaining 270 g of white solid glutaric acid dimenthyl ester,The yield was 90%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With toluene-4-sulfonic acid In cyclohexane at 85 - 130℃; for 5h; | 2.1; 2.2; 2.3 (1)Ingredient process: using menthol and malic acid as raw materials, using cyclohexane as solvent and p-toluenesulfonic acid as catalyst, respectively, weigh 60g of malic acid,Cyclohexane 2L, p-toluenesulfonic acid 2.4g and 156g menthol, p-toluenesulfonic acid,Malic acid and cyclohexane were added to the reactor and stirred to 130 ° C.After the solid is completely melted,Add menthol 156 to a temperature of about 85 ° C.Forming a mixture of reactant systems;(2)The menthol esterification reaction is carried out in a reaction kettle,Controlling the reaction temperature of the reactant system mixture in the step (1) is 120 ° C, heating the reflux water, the reaction time is 5h;The menthol esterification reaction of the present embodiment is carried out in a solution;(3)After the end of the esterification reaction, the reaction product was cooled to room temperature and washed with saturated NaHCO3 until no bubbles.After completely dissolving the solid matter in the aqueous phase with diethyl ether,Wash with neutral NaCl solution until neutral, take the upper organic phase and evaporate the ether and recrystallize with ethanol.Obtained 170 g of a white solid.The yield was 90%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99.8% | With ruthenium trichloride; C22H32FeP2 In toluene at 150℃; for 10h; Inert atmosphere; Autoclave; | 1; 5; 6; 7; 8; 9; 10; 11; 12; 13; 14; 15 Example 1 41.4 mg (0.1 mmol) of a bisphosphine ligand (chiral phosphine ligand compound (1)),20.7 mg (0.1 mmol) of RuCl3 was dissolved in 15 mL of toluene and transferred to a 50 mL reaction kettle to give 30.44 g (0.2 mol) of racemic isopulegol(ee = 0%, L-isopulegol / D-isopulegol = 1:1 (mol)) was injected into the reaction vessel, and the pressure was adjusted to 1 bar after replacing the gas in the autoclave three times with nitrogen.After stirring, the reaction was carried out at 150 ° C for 10 h, and the conversion of L-isopulegol was 99.9% by gas chromatography.D-isopulegol was not converted, the product was L-menthone, and the optical purity was 99ee%.The formation of isomenthone was 99.8% in terms of L-isomenthol in the starting material. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
61% | With rhodium(III) chloride trihydrate; copper diacetate; In N,N-dimethyl-formamide; at 90℃; under 760.051 Torr; for 10h;Sealed tube; | AddN-pyrimidinylpurine 1a (0.2 mmol), RhCl3•3H2O (0.004 mmol), Cu(OAc)2(0.4 mmol) and2-isopropyl-5-methylcyclohexanol 2r (1.0 mmol) to 2.0 mL DMF, in a Young tube setafter the change of carbon monoxide three times, charged with carbon monoxide (1 atm), the reaction and after 90 deg.] C oil bath for 10 hours, the reaction was stopped, to be antisolution was cooled to room temperature, ethyl acetate and saturated The saline is washed and extracted several times.The organic phase was dried over anhydrous sodium sulfateand filtered.The solvent was evaporated to dryness, and ethyl acetate / petroleum ether (1:10to 1:1).The product was a white solid with a yield of 61%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88.7% | With tetrabutoxytitanium; In toluene; at 110℃; for 33h;Green chemistry; | General procedure: 0.25 mol of menthol, 0.1 mol of glutaric acid and toluene as a solvent are mixed and used as a catalyst. titanium butoxide1 mol% / acid the reaction was carried out at 110 C. for about 33 hours.After the reaction was completed, ether and saturated sodium bicarbonate solution were added,Separation extraction using an acid-base reaction was performed.After repeated extraction, the organic layer is washed with water,Dry with MgSO 4.After filtering through the filtration process,The ether was removed through a vacuum rotary evaporator,By removing the unreacted menthol through vacuum distillation, the compound represented by [Formula 1-1] was finally obtained in a yield of 78.1%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
69.6% | With tetrabutoxytitanium In toluene at 110℃; for 33h; Green chemistry; | 1.1-2 General procedure: 0.25 mol of menthol, 0.1 mol of glutaric acid and toluene as a solvent are mixed and used as a catalyst. titanium butoxide1 mol% / acid the reaction was carried out at 110 ° C. for about 33 hours.After the reaction was completed, ether and saturated sodium bicarbonate solution were added,Separation extraction using an acid-base reaction was performed.After repeated extraction, the organic layer is washed with water,Dry with MgSO 4.After filtering through the filtration process,The ether was removed through a vacuum rotary evaporator,By removing the unreacted menthol through vacuum distillation, the compound represented by [Formula 1-1] was finally obtained in a yield of 78.1%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
71.4% | With tetrabutoxytitanium In toluene at 110℃; for 33h; Green chemistry; | 1.1-2 General procedure: 0.25 mol of menthol, 0.1 mol of glutaric acid and toluene as a solvent are mixed and used as a catalyst. titanium butoxide1 mol% / acid the reaction was carried out at 110 ° C. for about 33 hours.After the reaction was completed, ether and saturated sodium bicarbonate solution were added,Separation extraction using an acid-base reaction was performed.After repeated extraction, the organic layer is washed with water,Dry with MgSO 4.After filtering through the filtration process,The ether was removed through a vacuum rotary evaporator,By removing the unreacted menthol through vacuum distillation, the compound represented by [Formula 1-1] was finally obtained in a yield of 78.1%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90.7% | With tetrabutoxytitanium In toluene at 110℃; for 33h; Green chemistry; | 1.1-2 General procedure: 0.25 mol of menthol, 0.1 mol of glutaric acid and toluene as a solvent are mixed and used as a catalyst. titanium butoxide1 mol% / acid the reaction was carried out at 110 ° C. for about 33 hours.After the reaction was completed, ether and saturated sodium bicarbonate solution were added,Separation extraction using an acid-base reaction was performed.After repeated extraction, the organic layer is washed with water,Dry with MgSO 4.After filtering through the filtration process,The ether was removed through a vacuum rotary evaporator,By removing the unreacted menthol through vacuum distillation, the compound represented by [Formula 1-1] was finally obtained in a yield of 78.1%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
81.5% | With tetrabutoxytitanium In toluene at 110℃; for 33h; Green chemistry; | 1.1-2 General procedure: 0.25 mol of menthol, 0.1 mol of glutaric acid and toluene as a solvent are mixed and used as a catalyst. titanium butoxide1 mol% / acid the reaction was carried out at 110 ° C. for about 33 hours.After the reaction was completed, ether and saturated sodium bicarbonate solution were added,Separation extraction using an acid-base reaction was performed.After repeated extraction, the organic layer is washed with water,Dry with MgSO 4.After filtering through the filtration process,The ether was removed through a vacuum rotary evaporator,By removing the unreacted menthol through vacuum distillation, the compound represented by [Formula 1-1] was finally obtained in a yield of 78.1%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | With hydroxide solution at 15℃; for 5h; | 2.3.4 4) Add the above compound D to 100mL 25% potassium hydroxide solution,The reaction was stirred at 15 ° C for 5h, then extracted twice with ether, and the ether layers were combined,After washing three times with water, drying with anhydrous sodium sulfate and distillation under reduced pressure to obtain L-menthol, the yield is 96%, ee% = 98%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With [Ru(PnOct3)4(H)2] In o-xylene at 130℃; for 12h; Inert atmosphere; Autoclave; | 1 Comparative Example 1 (CN 104603095 Preparation Example 4) Under inert conditions, 404 mg of [Ru (PnOct3) 4 (H) 2],3.6g of isopulegol and 10ml of o-xylene (anhydrous) were weighed into a 50ml glass autoclave.The reaction mixture was then stirred at an oil bath temperature of 130 ° C under autogenous pressure (0.5 bar positive pressure) for 12 hours.After the reaction, the conversion and yield (area%) of menthone (sum of isomers) were determined by gas chromatography.The conversion of isopulegol was 64.5%, and the selectivity of menthol (65.8% (-)-menthol, 34.2% (+)-isomenthol isomer mixture) was 46.3%.Selectivity of secondary components: menthol 30.2%, isopupleone 14.4%, total selectivity (menthol + menthol + isopupleone) 90.9%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With pyridine In dichloromethane at -10℃; for 4h; | 1-3 Example 3 Add 20ml of dichloromethane to the reactor, place the instrument in a cold well and set the temperature to -10°C, and turn on the stirring blade, then add 3.12g (0.02mol) L-menthol, 2.376g (0.008mol) triphosgene, After stirring to complete dissolution, add 1.921 g (0.024 mol) of pyridine and 40 ml of dichloromethane into the dropping funnel and mix them evenly. The solution is slowly added dropwise to the reactor, and the dropping rate is controlled at 1 drop per second. Stir After 4 hours of reaction, TLC detection is used to confirm that the reaction is complete and ready to start the second step of the reaction. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
63% | Stage #1: menthol With sodium hydride In N,N-dimethyl-formamide at 0℃; for 0.5h; Inert atmosphere; Stage #2: 7-bromohept-1-yne In N,N-dimethyl-formamide at 0 - 20℃; for 12h; Inert atmosphere; |
Tags: 89-78-1 synthesis path| 89-78-1 SDS| 89-78-1 COA| 89-78-1 purity| 89-78-1 application| 89-78-1 NMR| 89-78-1 COA| 89-78-1 structure
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H411 | Toxic to aquatic life with long-lasting effects |
H412 | Harmful to aquatic life with long-lasting effects |
H413 | May cause long-lasting harmful effects to aquatic life |
H420 | Harms public health and the environment by destroying ozone in the upper atmosphere |
Sorry,this product has been discontinued.
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