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CAS No. : | 2672-58-4 | MDL No. : | MFCD00008434 |
Formula : | C12H12O6 | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | RGCHNYAILFZUPL-UHFFFAOYSA-N |
M.W : | 252.22 | Pubchem ID : | 75881 |
Synonyms : |
|
Num. heavy atoms : | 18 |
Num. arom. heavy atoms : | 6 |
Fraction Csp3 : | 0.25 |
Num. rotatable bonds : | 6 |
Num. H-bond acceptors : | 6.0 |
Num. H-bond donors : | 0.0 |
Molar Refractivity : | 60.28 |
TPSA : | 78.9 Ų |
GI absorption : | High |
BBB permeant : | No |
P-gp substrate : | No |
CYP1A2 inhibitor : | Yes |
CYP2C19 inhibitor : | No |
CYP2C9 inhibitor : | No |
CYP2D6 inhibitor : | No |
CYP3A4 inhibitor : | No |
Log Kp (skin permeation) : | -6.79 cm/s |
Log Po/w (iLOGP) : | 2.63 |
Log Po/w (XLOGP3) : | 1.48 |
Log Po/w (WLOGP) : | 1.05 |
Log Po/w (MLOGP) : | 1.74 |
Log Po/w (SILICOS-IT) : | 1.64 |
Consensus Log Po/w : | 1.71 |
Lipinski : | 0.0 |
Ghose : | None |
Veber : | 0.0 |
Egan : | 0.0 |
Muegge : | 0.0 |
Bioavailability Score : | 0.55 |
Log S (ESOL) : | -2.19 |
Solubility : | 1.64 mg/ml ; 0.0065 mol/l |
Class : | Soluble |
Log S (Ali) : | -2.74 |
Solubility : | 0.455 mg/ml ; 0.0018 mol/l |
Class : | Soluble |
Log S (SILICOS-IT) : | -2.63 |
Solubility : | 0.589 mg/ml ; 0.00233 mol/l |
Class : | Soluble |
PAINS : | 0.0 alert |
Brenk : | 1.0 alert |
Leadlikeness : | 0.0 |
Synthetic accessibility : | 1.7 |
Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P280-P305+P351+P338 | UN#: | N/A |
Hazard Statements: | H302 | Packing Group: | N/A |
GHS Pictogram: |
* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
83% | With water; sodium hydroxide In methanol for 8 h; | The trimethyl benzene-1,3,5-tricarboxylate (62 g, 246 mmol) was dissolved in MeOH (800 mL), aq. sodium hydroxide (221 mL, 221 mmol)-(1N) was slowly added. The suspension was stirred vigorously and slowly dissolved during 8 hours. The reaction was left stirred at room temperature for 18 hours, then the solvent was removed in vacuo. (1044) DCM (600 mL) was added to the solid and the organic phase was washed with sat. NaHCO3 (3×500 mL) 3 layers in the separation funnel—solution was filtered and solid on the funnel was rinsed with DCM. The LC-MS of the crude confirmed that MW was of the desired product (MW:238; 48.8 g; yield 83percent). The LC-MS analysis of material from the organic layer showed a mixture of the desired product as well as over-hydrolyzed product (MW: 224; 9 g), and analysis of material from the aqueous layer showed start material. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With sulfuric acid | |
100% | With sulfuric acid at 72℃; | 1 Benzene-1,3,5-tricarboxylic acid (50 g, 238 mmol) was dissolved in MeOH, and then conc. sulfuric acid (12.68 mL, 238 mmol) was slowly added. The solution became clear after 30 minutes of reflux and was left stirring at 72° C. for overnight. Solvent was removed under reduced pressure, the residue was dissolved in chloroform (2×800 mL) and washed with NaHCO3, then the organic solvent was removed in vacuo. (60 g, 100% yield). |
99% | With sulfuric acid for 24h; Heating; |
99% | With sulfuric acid for 24h; Reflux; | |
98% | With sulfuric acid Heating; | |
98% | Acidic conditions; | 2; 3; 10; 12.a Branched malonate molecules 1 and 2 were produced according to the schemes shown in FIGS. 9-10. EXAMPLE 3 The synthesis of a tripodal trismalonate tether (5) is shown in FIG. 12. Triol 4 was synthesized starting from benzene-1,3,5-tricarboxylic acid according to a literature procedure. Treatment of 4 with methyl 3-chloro-3-oxopropionate in the presence of pyridine in CH2Cl2, followed by flash column chromatographic purification, afforded pure 5 in 72% yield. |
98% | With sulfuric acid for 12h; Reflux; | |
98.6% | With sulfuric acid for 24h; Reflux; | |
97% | With sulfuric acid for 18h; Heating; | |
97% | With sulfuric acid at 70℃; for 6h; | |
96% | With sulfuric acid In tetrachloromethane Heating; | |
96% | With sulfuric acid at 80℃; for 24h; | |
96% | With sulfuric acid In water at 73℃; for 24h; | 20.00 g of trimesic acid was dissolved in 350 mL of methanol, 5 mL of 18 mol / L concentrated sulfuric acid catalyst was added slowly and refluxed at 73 oC for 24 h.The solvent was evaporated under reduced pressure, 60 mL of chloroform was added until just dissolved, and 130 mL of a 100 g / L saturated sodium bicarbonate solution was added until the pH was neutral.The organic phase was separated and the solvent was evaporated under reduced pressure and dried under vacuum at 80 ° C to give 23.03 gTrimellitic acid methyl ester(96% yield). |
96% | With sulfuric acid for 12h; Reflux; | |
95% | With sulfuric acid for 24h; Heating; | |
95% | With sulfuric acid for 24h; Reflux; | |
94% | With sulfuric acid for 20h; Reflux; | |
94% | With sulfuric acid at 60℃; | |
93% | With sulfuric acid for 6h; Reflux; | |
93% | With sulfuric acid for 24h; Reflux; | 1,3,5-Tris(methoxycarbonyl)benzene (1) 1,3,5-Benzenetricarboxylic acid (2 g, 9.52 mmol), methanol(40 mL), and concentrated sulfuric acid (0.5 mL) were mixed and then refluxed for 24 h. The solvent was evaporated, and the residue was dissolved in chloroform(50 mL) and then washed with a saturated solution of potassium carbonate (40 mL). The solvent was removed under reduced pressure to afford 1 as a white powder(2.23 g, 93 % yield). 1H NMR (300 MHz, CDCl3):d = 8.84 (s, 3H), 3.97 (s, 9H) ppm. 13C NMR (75.4 MHz,CDCl3): d = 165.36, 134.54, 131.17, 52.58 ppm. MS (GC/MS): m/z = 252 [M], 221 [M-OCH3]. The analytical data are consistent with the literature [13]. |
92% | With sulfuric acid for 24h; Heating; | |
92% | With sulfuric acid for 24h; Reflux; | |
91% | With sulfuric acid at 58℃; for 16h; Microwave irradiation; Reflux; | |
90% | With sulfuric acid at 120℃; for 24h; | |
90% | With sulfuric acid at 85℃; for 24h; | |
88% | With hydrogenchloride for 1h; y; | |
88% | With sulfuric acid for 24h; Reflux; | |
87% | With sulfuric acid Heating / reflux; | 3 In a flask equipped with a condenser and a drying tube 1,3,5- s benzenetricarboxylic acid 49 (22.12 g, 0.1 mol) was suspended in methanol (250 ml), concentrated sulphuric acid (25 ml) was added, and the mixture was refluxed over night.After cooling to 0°C the white precipitate was filtered off, washed with cold water, dissolved in CHCl3, and dried over MgSO4. Removal of the solvent gave the desired product (22.05 g,87%) as a white powder; mp 142-144°C (lit. 144-144.5°C); 1H NMR (300 MHz, CDCl3) δ o 3.99 (s, 3H, CH3), 8.85 (s, IH, aromat. H). |
With hydrogenchloride | ||
With sulfuric acid | ||
With sulfuric acid | ||
With sulfuric acid | ||
5.72 g | With sulfuric acid for 6h; Reflux; | Synthesis of 1,3,5-tris(hydroxyl methyl) benzene Trimesic acid (5 g, 23.8 mmol) was suspended in methanol (15 mL) and heated to reflux. When a clear solution obtained,1.6 mL of con.H2SO4 was added slowly and the mixture was refluxed for 6 h. After 3 h, white solid get precipitated from the solution. The mixture was cooled to room temperature, slowly neutralized with saturated NaHCO3 solution, filtered and washed with excess water until the aqueous layer turned neutral. It was then dried to yield a white solid of trimethyl-1,3,5-benzenetricarboxylate (5.72 g). LiAlH4 tablets (2.5 g, 66 mmol) were suspended and refluxed in dry THF (50 mL) under an inert N2 atmosphere. Trimethyl-1,3,5-benzenetricarboxylate (5 g, 20 mmol) was dissolved in 100 mL dry THF and added to the suspension in 1 h. The solution was then refluxed for 24 h, cooled to 0 C and acidified with 1MHCl. THFwas removed under reduced pressure and the aqueous suspension (100 mL) thus obtained was extracted with ethyl acetate for 48 h in a liquideliquid extractor to yield 1,3,5-trimethylolbenzene which appeared as colorless crystals in room temperature. The mother liquor was concentrated to yield second fraction. Both the fractions were NMR pure and the combined yield was 4.96 g. |
With sulfuric acid for 6h; Reflux; | Synthesis of dendron units (a) Trimethyl-1,3,5-benzenetricarboxylate: Trimesic acid (10 g, 47.5 mmol) was suspended in MeOH (30 mL) and heated to reflux. When a clear solution was obtained, 1.6 mL of conc. H2SO4 was added drop wise and the mixture was allowed to reflux for 6 h. After 3 h, white solid got precipitated from the solution. The mixture was further cooled to RT, slowly neutralized with sat. NaHCO3 solution filtered and washed with excess water until the aqueous layer turned neutral. It was then dried to yield a white solid. | |
With sulfuric acid | ||
With sulfuric acid | ||
With sulfuric acid for 9h; Reflux; | 1.1.a Example 1(1) 3,5-Dicarboxylic acid-1-Synthesis of methyl benzoate To a thermometer, stirrer,Condensate tube and water separator in the four bottles in order to accurately weigh benzeneTricarboxylic acid,Excess of methanol as solvent, then add concentrated H2SO4, which are benzeneTerephthalic acid and methanol mass ratio of 1: 2, trimesic acid and concentrated H2SO4 molar ratio of 1: 0.04, reflux 9h, plus Na2CO3 to neutral,Ethyl acetate, dried over MgSO4, filtered to remove the solvent,Preparation of bothTrimethyl trimellitate. | |
2 g | With toluene-4-sulfonic acid for 48h; Inert atmosphere; Reflux; | |
With sulfuric acid at 80℃; for 24h; | ||
In toluene Reflux; Dean-Stark; | ||
With sulfuric acid at 80℃; for 24h; Inert atmosphere; | ||
With sulfuric acid for 6h; Reflux; | ||
With sulfuric acid Reflux; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | In tetrahydrofuran; methanol; | EXAMPLE 5 STR20 1,3,5-tris(hydroxymethyl)benzene To a stirring solution of trimethyl 1,3,5-benzenetricarboxylate (10.45 g, 41.4 mmol) in 70 ml of anhydrous THF is added at room temperature a 10M solution of borane-methyl sulfide complex (25 ml, 248 mmol) and the solution is heated to reflux for 3 h. The mixture is then added slowly to 50 ml of MeOH and the resulting mixture is heated at 70 C. for 10 min to remove the methyl sulfide. Evaporation of solvent, washing twice with 50 ml of MeOH and evaporation of MeOH gives 1,3,5-tris(hydroxymethyl)benzene (6.96 g, 100%). 1 H NMR (D2 O): delta 4.52 (6H, s), 7.15 (3H, s). |
100% | In tetrahydrofuran; methanol; | EXAMPLE 5 1,3,5-tris(hydroxymethyl)benzene To a stirring solution of trimethyl 1,3,5-benzenetricarboxylate (10.45 g, 41.4 mmol) in 70 ml of anhydrous THF is added at room temperature a 10M solution of borane-methyl sulfide complex (25 ml, 248 mmol) and the solution is heated to reflux for 3h. The mixture is then added slowly to 50 ml of MeOH and the resulting mixture is heated at 70C for 10 min to remove the methyl sulfide. Evaporation of solvent, washing twice with 50 ml of MeOH and evaporation of MeOH gives 1,3,5-tris(hydroxymethyl)benzene (6.96 g, 100%). 1H NMR (D2O): delta 4.52 (6H, s), 7.15 (3H, s). |
96% | With lithium aluminium tetrahydride; In tetrahydrofuran; at 70℃; for 24h;Cooling with ice; Inert atmosphere; | Take 8.00 g of trimesic acid methyl ester 35 oC dissolved in 80 mL of anhydrous tetrahydrofuran,Under nitrogen protection by a constant pressure funnel was slowly added dropwise to 3.00 g of lithium aluminum hydride and 300 mL of anhydrous tetrahydrofuran mixture,The dropwise addition was carried out in ice-salt bath, and the temperature was restored to room temperature after the addition was completed. The mixture was stirred at reflux for 70 oC for 24 h,The reaction was carried out under magnetically stirred ice bath-reflux integrated nitrogen protection. After the reaction, the reaction was quenched with about 100 mL of distilled water, the mixture was suction filtered, the filter cake was washed three times with 100 mL of methanol, and the filtrate was distilled under reduced pressure ,80 oC vacuum drying, 5.12 g are tribenzyl alcohol(96% yield). |
83% | With LiAlH4; In tetrahydrofuran; | Synthesis of 1,3,5-Tris(hydroxymethyl)benzene (50)(Y. Yamaqiwa, Y. Koreishi. S. Kivozumi, M. Kobavashi, T. Kamikawa, M. Tsukino, H. Goi M. Yamamaoto, M. Munakata. Bull. Chem. Soc. Jpn. 1996, 69, 3317-3323; J. Houk, G. Whitesides. J. Am. Chem. Soc. 1987, 109, 6825-6836) A solution of 1,3,5-tris(methoxycarbonyl)benzene (10.09 g, 40 mmol) in dry THF (400 ml) was added over a period of 3h to a suspension of LiAlH4 (4.03 g, 0.1 mol) in dry THF (300 ml) under N2. After stirring over night at room temperature, the reaction mixture was cooled to 0 C., hydrolyzed with water (4 ml), 2M NaOH (4 ml) and water (12 ml), filtered, and the filter cake washed thoroughly with THF. The combined filtrates were concentrated and the crude product was recrystallized from hot (not boiling) ethanol to afford 50(5.59 g, 83%) as white needles; mp 76-77 C. (lit. 77-78 C.) 1H NMR (300 MHz, DMSO-d6) delta4.49 (d, 3H, J4.8 Hz, CH2), 5.30 (t, 1H, J5.4 Hz, OH), 7.14 (s, 1H, aromat. H). |
83% | A solution of l,3,5-tris(methoxycarbonyl)benzene (10.09 g, 40 mmol) in dry THF (400 ml) was added over a period of 3h to a suspension of LiAlH4 (4.03 g, 0.1 mol) in dry THF (300 ml) under N2. After stirring over night at room temperature, the reaction mixture was cooled to 0C, hydrolysed with water (4 ml), 2M NaOH (4 ml) and water (12 0 ml), filtered, and the filter cake washed thoroughly with THF. The combined filtrates were concentrated and the crude product was recrystallized from hot (not boiling) ethanol to afford 50 (5.59 g, 83%) as white needles; mp 76-770C (lit. 77-78C) 1H NMR (300 MHz, DMSO- d6) delta 4.49 (d, 3H, J 4.8 Hz, CH2), 5.30 (t, IH, J 5.4 Hz, OH), 7.14 (s, IH, aromat. H). | |
78% | With lithium aluminium tetrahydride; In tetrahydrofuran; | Branched malonate molecules 1 and 2 were produced according to the schemes shown in FIGS. 9-10. EXAMPLE 3 The synthesis of a tripodal trismalonate tether (5) is shown in FIG. 12. Triol 4 was synthesized starting from benzene-1,3,5-tricarboxylic acid according to a literature procedure. Treatment of 4 with methyl 3-chloro-3-oxopropionate in the presence of pyridine in CH2Cl2, followed by flash column chromatographic purification, afforded pure 5 in 72% yield. |
73% | Trimethyl-1 ,3,5- benzenetricarboxylate 14 (1.98 g, 7.83 mmol) in dry THF (30 mL) was added through a pressure-equalized addition funnel into a stirring suspension of LiAIH4 (0.95 g, 24.9 mmol) in dry THF (65 mL) at O0C under an argon atmosphere. The mixture was allowed to warm to rt and stirred for 4 hours. 1H NMR (CDCI3) was used to monitor the reaction. After determining a large amount of starting material remained, additional LiAIH4 (0.50 g, 13.1 mmol) was added to the reaction mixture and the reaction was allowed to proceed at RT for an additional 4 hours. 1H NMR (CDCI3) was used to determine if reaction was complete. After the reaction was complete, MeOH (25 mL) was used to quench the reaction. The suspension was filtered using Celite and the Celite was washed with MeOH (100 mL). The filtrate was concentrated under reduced pressure. The residue was stirred in THF (30 mL), KHSO4 (3.53g, 26 mmol) and Celite (1.53 g, 25.4 mmol) for 30 minutes. The suspension was filtered and washed with MeOH (50 mL). Solvents were removed under reduced pressure. The resulting solid was dissolved in hot ethyl acetate and filtered. The solid that remained at the filter was collected, dried and to yield triol 15 (0.954 g, 5.68 mmol, 73%). 1H NMR (DMSO): delta 7.22 (s, 3H), 5,17 (br s, 3H), 4.48 (s, 6H). | |
In tetrahydrofuran; | Preparation 1 1,3,5-Tris(hydroxymethyl)benzene A solution of trimethyl 1,3,5-benzenetricarboxylate (8.83 g, 0.035 M; Aldrich) in THF (125 mL) is added dropwise over a period of 45 minutes to a stirred mixture of lithium aluminum hydride (3.98 g, 0.105 M) and dry THF (150 mL) under a nitrogen atmosphere. The initial phase of the addition results in vigorous reaction and consequently the addition is very slow at first. As the ester solution is added, an orange mass forms when the drops came in contact with the LiAlH4 mixture. A yellowish-green mixture results and is stirred at room temperature. The excess LiAlH4 is quenched carefully by the addition of ethyl acetate and the resulting mixture is acidified with aqueous 2N HCl solution until the pH is <3 and aluminum salts have dissolved. The layers are separated and the aqueous layer is extracted 3 times with additional ethyl acetate and then with methylene chloride. The organic extract layers are dried (sodium sulfate), filtered, and concentrated under reduced pressure to give a white solid (2.98 g, 51%). Recrystallization from acetonitrile-methylene chloride gives the title compound as white crystals (1.13 g) which appear to be hygroscopic when collected by suction filtration. The crystals are dried several days over P2 O5 in a vacuum desiccator after which they have amp of 76.5-78 C. | |
With lithium aluminium tetrahydride; In tetrahydrofuran; | a solution of triphenylphosphine (577 mg, 2.2 mmol) in anhydrous THF (5 mL) was added diethyl azodicarboxylate (2.2 M in toluene, 791 muL, 1.7 mmol) dropwise at 0C. After stirred at 0C for 50 minutes, a solution of 1,3,5-tri(hydroxymethyl)benzene (269 mg, 1.6 mmol, prepared by reduction of trimethyl 1,3,5-benzenetricarboxylate with lithium aluminum hydride in THF, co-evaporated with dry benzene and dried on high vacuum for couple hours before use) and thioacetic acid (108 muL, 1.45 mmol) in dry THF (4 mL) was added dropwise. After 1 hour, the ice/water bath was removed and the reaction was stirred at room temperature for 15 hours. The solvents were removed by rotary evaporation in vacuo. The residue was purified by flash chromatography to give 5-acetylthiomethyl-1,3-bis(hydroxymethyl)-benzene as colorless solid (110 mg). 1H NMR (400 Hz, CDCl3): delta 7.13-6.99 (m, 3H), 4.45 (apt, J = 20.4 Hz, 4H), 3.98 (apt, J = 20.4 Hz, 4H), 3.73 (bs, 2H), 2.24 (apt, J = 20.4 Hz, 3H); MS (ESI): m/z 249.0 (M + Na)+. | |
4.96 g | Trimesic acid (5 g, 23.8 mmol) was suspended in methanol (15 mL) and heated to reflux. When a clear solution obtained, 1.6 mL of con.H2SO4 was added slowly and the mixture was refluxed for 6 h. After 3 h, white solid get precipitated from the solution. The mixture was cooled to room temperature, slowly neutralized with saturated NaHCO3 solution, filtered and washed with excess water until the aqueous layer turned neutral. It was then dried to yield a white solid of trimethyl-1,3,5-benzenetricarboxylate (5.72 g). LiAlH4 tablets (2.5 g, 66 mmol) were suspended and refluxed in dry THF (50 mL) under an inert N2 atmosphere. Trimethyl-1,3,5-benzenetricarboxylate (5 g, 20 mmol) was dissolved in 100 mL dry THF and added to the suspension in 1 h. The solution was then refluxed for 24 h, cooled to 0 C and acidified with 1 M HCl. THF was removed under reduced pressure and the aqueous suspension (100 mL) thus obtained was extracted with ethyl acetate for 48 h in a liquid-liquid extractor to yield 1,3,5-trimethylolbenzene which appeared as colorless crystals in room temperature. The mother liquor was concentrated to yield second fraction. Both the fractions were NMR pure and the combined yield was 4.96 g. The formation of ligand was confirmed via 1H NMR. 1H NMR (300 MHz, DMSO-d6, 25 C): delta = 7.096 (s, 3 H), 5.21 (t, J(H,H) = 5.6 Hz, 3 H), 4.45 (d, J = 5.6 Hz, 6 H). | |
With lithium aluminium tetrahydride; In tetrahydrofuran; for 24h;Inert atmosphere; Reflux; | A lithium aluminum hydride (0.45 g, 11.88 mmol) was added to 20 mL of dry THF. Then solution of 1 (0.5 g,1.98 mmol) in 20 mL of dry THF was added dropwise at room temperature under stirring and an atmosphere of Argon. After dropwise addition was completed, the mixture was heated to reflux for 24 h. The excess of reducing agent was destroyed by slow addition of water (5 mL) and the solvent was evaporated. Then 15 mL of a 48 % HBr solution and 25 mL of toluene were added and heated to reflex for 24 h. The organic layer was separated and theaqueous portion was extracted several times with diethylether (3 9 50 mL). The organic layers were combined and removed under reduced pressure. The crude material was purified through a column chromatography of silica gel with a 1:1 mixture of n-hexane: toluene as an eluent. The solvents were evaporated under high vacuum to afford 0.66 g (94 % yield) of 2. 1H NMR (300 MHz, CDCl3):d = 7.35 (s, 3H), 4.46 (s, 6H) ppm. 13C NMR (75.4 MHz,CDCl3): d = 139.06, 129.57, 32.16 ppm. MS (CG/MS): m/z = 356 [M], 277 [M-Br], 196 [M-2Br], 115 [M-3Br]. The analytical data are consistent with those in the literature[13]. | |
5.1 g | With lithium aluminium tetrahydride; In tetrahydrofuran; for 24h;Inert atmosphere; Reflux; | (b) 1,3,5-Tris(hydroxymethyl)benzene: LiAlH4 tablets (5 g, 132 mmol) were suspended and refluxed in dry THF (100 mL) under inert atmosphere of N2 gas. To this suspension, (10 g, 40 mmol) dissolved in 100 mL dry THF was added slowly over 1 h. The solution was then refluxed for 24 h, cooled to 0 C and acidified with 1 M HCl. THF was removed under reduced pressure and the aqueous suspension (100 mL) thus obtained was extracted with ethyl acetate for 48 h in a liquid e liquid extractor to yield 1,3,5-tri(methylol)benzene which appeared as colorless crystals at room temperature. The mother liquor was concentrated to yield second fraction of same product. Both the fractions were NMR pure and the combined yield obtained was 5.1 g. The formation of ligand was confirmed by 1H and 13C NMR analysis. 1H NMR (300 MHz, DMSO-d6,25C) :d 7.096 (s, 3H), 5.21 (t ,J(H,H)5.6Hz, 3H), 4.45 (d,J5.6 Hz, 6H); 13C NMR (63 MHz, DMSO-d6, 25C):d142.9,123.8, 63.9 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
52.8% | With lithium tetrahydridoborate In tetrahydrofuran at 80℃; for 3h; | Compound13-2 Compound13-1(4.5 g, 17.84 mmol) was added toa suspension ofLiBH4(583mg, 26.77 mmol) in anhydrous THF (70 mL) at room temperature. The reaction mixture was heated to reflux for 3 hrs before cooled to room temperature and quenched with saturated ammonium chloride aqueous solution (30 mL). The layers were separated and the aqueous layer was extracted with ethyl acetate(3 × 50 mL). The combined organic layerswerewashed with saturated brine, dried over anhydrous Na2SO4, and concentrated under reduced pressure. The residue was purifiedon silica gel column elution (30-70% EtOAc in hexanes) afforded compound13-2(1.85 g, 52.8% yield) as a whitesolid.1H NMR (400 MHz, CDCl3) δ 7.96 (s, 2H), 7.61 (s, 1H), 4.79 (m, 4H), 3.96 (s, 3H), 1.96 (t,J= 5.6Hz, 2H). |
52.8% | With lithium tetrahydridoborate In tetrahydrofuran at 80℃; for 3h; | Compound13-2 Compound13-1(4.5 g, 17.84 mmol) was added toa suspension ofLiBH4(583mg, 26.77 mmol) in anhydrous THF (70 mL) at room temperature. The reaction mixture was heated to reflux for 3 hrs before cooled to room temperature and quenched with saturated ammonium chloride aqueous solution (30 mL). The layers were separated and the aqueous layer was extracted with ethyl acetate(3 × 50 mL). The combined organic layerswerewashed with saturated brine, dried over anhydrous Na2SO4, and concentrated under reduced pressure. The residue was purifiedon silica gel column elution (30-70% EtOAc in hexanes) afforded compound13-2(1.85 g, 52.8% yield) as a whitesolid.1H NMR (400 MHz, CDCl3) δ 7.96 (s, 2H), 7.61 (s, 1H), 4.79 (m, 4H), 3.96 (s, 3H), 1.96 (t,J= 5.6Hz, 2H). |
43.1% | Stage #1: 1,3,5-tris-(methoxycarbonyl)benzene With lithium aluminium hydride In tetrahydrofuran at 0 - 20℃; for 3h; Stage #2: With sodium hydroxide In tetrahydrofuran; water monomer | 6-24.10.1 Benzene-1,3, 5-tricarboxylic acid trimethylester (1.010 g, 4.003 mmol) was dissolved in tetrahydrofuran (15ml). Thereafter, the temperature was lowered into OC, and therein lithium aluminium hydride (0.160 g, 4.003 mmol) was slowly added, and the reaction mixture was stirred at room temperature for 3 hours. Water (0.15 ml) and 15% NAOH aqueous solution (0.15 ml) were slowly added to quench the reaction. Aqueous solution (0.45 ml) was added again. Solvent was concentrated under reduced pressure. The residue was purified by column chromatography (hexane: ethyl acetate = 1 : 2), to give 0.34 g (yield: 43. 1%, colorless liquid) of the target compound. IH NMR (400MHZ, CD30D) : 53. 91 (s, 3H), 4.66 (s, 4H), 7.59 (s, 1H), 7.93 (s, 2H) |
With lithium aluminium hydride; diethyl ether | ||
2.1 g | With lithium aluminium hydride In tetrahydrofuran at 20℃; Inert atmosphere; Cooling with ice; | 47-1 Methyl 3,5-bis(hydroxymethyl)benzoate Methyl 3,5-bis(hydroxymethyl)benzoate [0562] A tetrahydrofuran solution (49 mL) of trimethyl 1,3,5-benzenetricarboxylate (5.0 g) was added to a tetrahydrofuran solution (50 mL) of lithium aluminium hydride (751 mg) under an argon atmosphere under ice-cooling, and then the mixture was stirred at room temperature for 1 hour. Water (0.8 mL), a 15% sodium hydroxide aqueous solution (0.8 mL), and water (2.3 mL) were added to the reaction solution and the suspension thus obtained was filtered off by Celite. The solvent was evaporated to obtain a title compound as a colorless powder (2.1 g). 1H-NMR (400 MHz, CDCl3) δ 1.78 (2H, t, J = 6.1 Hz), 3.93 (3H, s), 4.77 (4H, d, J = 6.1 Hz), 7.61 (1H, s), 7.96 (2H, s) |
Multi-step reaction with 2 steps 1: water monomer; sodium hydroxide / methanol / 3 h / Reflux; Inert atmosphere 2: dimethylsulfide borane complex / tetrahydrofuran / 0 - 25 °C / Inert atmosphere | ||
Multi-step reaction with 2 steps 1: sodium hydroxide; water monomer / methanol / 20 °C 2: BH3 / tetrahydrofuran / 25 h / 0 - 20 °C / Inert atmosphere | ||
Multi-step reaction with 2 steps 1: water monomer; sodium hydroxide / methanol / 3 h / Inert atmosphere; Reflux 2: dimethylsulfide borane complex / tetrahydrofuran / 0 - 20 °C / Inert atmosphere | ||
Multi-step reaction with 2 steps 1: sodium hydroxide / methanol; water monomer 2: dimethylsulfide borane complex / tetrahydrofuran / 0 °C / Inert atmosphere |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
69% | With sodium tetrahydroborate In tetrahydrofuran; methanol for 1.33333h; Inert atmosphere; Reflux; | |
63% | Stage #1: 1,3,5-tris-(methoxycarbonyl)benzene With lithium borohydride In tetrahydrofuran; acetic acid methyl ester at 50℃; for 3h; Stage #2: With water; acetic acid In tetrahydrofuran; acetic acid methyl ester | Synthesis of dimethyl-(5-hydroxymethyl)isophthalate QOAH-2 was accomplished according to the following synthesis scheme (0.1 mol) of trimethyl 1,3,5 benzenetricarboxylate was dissolved in 85 mL of methyl acetate at 50° C. 40.5 ml (0.08 mol) lithiumborohydride 2.0 M in THF was added drop wise and the mixture was stirred during 3 hour at 50° C. After this period 5.3 gram acetic acid (0.088 mol) and 3 mL water were added. The methyl acetate and THF were evaporated, 50 ml water and 50 ml n-hexane were added. The product QAOH-2 was filtered and washed with a small volume water and n-hexane. The yield was 63%. |
61% | With methanol; sodium tetrahydroborate In tetrahydrofuran for 0.5h; Inert atmosphere; Reflux; | 4 Preparation of dimethyl 5-hydroxymethylisophthalate (32) Preparation of dimethyl 5-hydroxymethylisophthalate (32) Trimethyl 1,3,5-benzenetricarboxylate (5.02 g, 19.9 mmol) was dissolved in THF (15 mL). The air was evacuated from the reaction system, and then Ar was charged therein. To the solution were added NaBH4 (901 mg, 23.8 mmol), and then a mixed solution of THF:MeOH (12.5 mL:3.7 mL) slowly dropwise. The reaction mixture was refluxed for 30 minutes. TLC was used to confirm the progress of the reaction. Then, the reaction was quenched with HCl (1N, 20 mL). The mixture was extracted with EtOAc. The organic layer was washed with a saturated sodium chloride aqueous solution, dried over anhydrous sodium sulfate, and evaporated under reduced pressure to remove the solvent. The residue was purified by neutral silica gel column chromatography (hexane:EtOAc =4:1 to 3:1) to isolate dimethyl 5-hydroxymethylisophthalate (32) (2.73 g, 61%) as white crystals. 1H-NMR (CDCl3, 400 MHz) δ = 8.60 (1H, s, Ar-H), 8.24 (2H, s, Ar-H), 4.82 (2H, d, J = 6.3 Hz, CH2O), 3.95 (6H, s, CH3CO2), 1.98 (1H, t, J= 6.3 Hz, OH) 13C-NMR (CDCl3, 100 MHz) δ = 166.2, 142.0, 131.9, 130.7, 129.7, 64.05, 52.37 |
57% | With sodium tetrahydroborate In tetrahydrofuran; methanol for 0.5h; Inert atmosphere; Reflux; | |
55% | With lithium borohydride In tetrahydrofuran at 0℃; Inert atmosphere; Reflux; | 13 Preparation of compound AMA-5a A homogeneous solution of trimethyl-1, 3, 5 -benzenetri carboxyl ate (34.28 g, 135.91 mmol) in dry THF at 0 °C under N2 atmosphere was treated with 4M L1BH4 in THF (16.99 mL, 67.95 mmol) and heated to reflux overnight. After the reaction was cooled to room temperature, the mixture was acidified with 4N HC1 (pH 2) and quenched with H2O (800 mL). The mixture was extracted with EA (800 mL X 2). The organic layer was dried over anhydrous Na2S04, filtered, and concentrated in vacuo. The residue was purified by flash chromatography (EA : HEX = 1 : 5 to 1 : 2) to give title compound AMA-5a (16.75 g, 55 %, 6.07 g Sm recovered) as a white solid. NMR (400 MHz, CDCh) S 8.59 (s, 1H), 8.23 (s, 2H), 4.81 (d, J= 6 Hz, 2H), 3.95 (s, 6H), 1.97 (t, J= 5.6 Hz, 1H). |
53.2% | With methanol; sodium tetrahydroborate In tetrahydrofuran for 0.5h; Reflux; | 1 Step 1. Preparation of dimethyl 5-(hydroxymethyl)isophthalate 59 Trimethyl benzene-1,3,5-tricarboxylate (58) (40 g, 159 mmol) and NaBH4 were stirred in THF at RT. MeOH (30 ml) in THF (120 ml) was added dropwise slowly. After complete addition the reaction was refluxed for 30 mins. After cooling the reaction was quenched with 1M HCl and extracted into EtOAc. The organics were washed sequentially with 1M HCl, NaHCO3, water and brine, dried (Na2SO4) and concentrated in-vacuo. The residue was purified by automated flash chromatography (50/50 EtOAc/hex) to give dimethyl 5-(hydroxymethyl)isophthalate (59) (20.5 g, 53.2%).1H NMR (400 MHz, CDCl3) d 8.59 (s, 1H), 8.23 (s, 2H), 4.81 (s, 2H), 3.95 (s, 6H). Product confirmed by MS (ESI +ve). |
53.2% | With methanol; sodium tetrahydroborate In tetrahydrofuran at 20℃; for 0.5h; Reflux; | 27.1 Step 1. Preparation of dimethyl 5-(hydroxymethyl)isophthalate 659 Trimethyl benzene-1,3,5-tricarboxylate (658) (40 g, 159 mmol) and NaBH4 were stirred in THF at RT. MeOH (30 ml) in THF (120 ml) was added dropwise slowly. After complete addition the reaction was refluxed for 30 mins. After cooling the reaction was quenched with 1M HCl and extracted into EtOAc. The organics were washed sequentially with 1M HCl, NaHCO3, water and brine, dried (Na2SO4) and concentrated in-vacuo. The residue was purified by automated flash chromatography (50/50 EtOAc/hex) to give dimethyl 5- (hydroxymethyl)isophthalate (659) (20.5 g, 53.2%).1H NMR (400 MHz, CDCl3) d 8.59 (s, 1H), 8.23 (s, 2H), 4.81 (s, 2H), 3.95 (s, 6H). Product confirmed by MS (ESI +ve). |
With lithium aluminium tetrahydride; diethyl ether | ||
Multi-step reaction with 2 steps 1: 76 percent / 0.1 M aq. NaOH / methanol / 18 h 2: 88 percent / borane-methyl sulfide / tetrahydrofuran / 24 h / 27 °C | ||
Multi-step reaction with 2 steps 1: sodium hydroxide / methanol 2: dimethyl sulfide borane / tetrahydrofuran / 20 °C | ||
Multi-step reaction with 2 steps 1: sodium hydroxide; water 2: dimethylsulfide borane complex | ||
Multi-step reaction with 2 steps 1: sodium hydroxide; water / methanol / 8 h 2: borane-THF / tetrahydrofuran / 24 h / 20 °C / Cooling with ice | ||
Multi-step reaction with 2 steps 1: sodium hydroxide / water; methanol / 18 h / 20 °C 2: dimethylsulfide borane complex / tetrahydrofuran / 24 h / 20 °C | ||
Multi-step reaction with 2 steps 1: sodium hydroxide; water / methanol / 22 h / 20 °C 2: dimethylsulfide borane complex / tetrahydrofuran / 25 h / 20 °C / Inert atmosphere | ||
0.6% | With sodium tetrahydroborate In tetrahydrofuran for 0.5h; Inert atmosphere; Reflux; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89.3% | With chloro-trimethyl-silane In butan-1-ol; benzene at 40℃; for 8h; regioselective reaction; | |
84% | With potassium hexafluorophosphate In acetonitrile at 60℃; for 69h; | |
75% | With piperazine; LACTIC ACID In N,N-dimethyl-formamide at 90℃; for 12h; |
52% | With germaniumtetrachloride; triethylamine In hexane for 2h; Heating; | |
21% | In dichloromethane | |
With [Ru(CO)4(η2-ethylene)] 1.) hexane, room temp., 2.) 160 - 180 deg C; Yield given; | ||
With ferric hydroxamate uptake protein component: A In tetrahydrofuran-d8; water-d2 at 60℃; for 72h; Inert atmosphere; regioselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | With trimethylamine In chloroform Heating; | |
64.5% | With triethylamine for 2h; ice bath; | |
2.4 g | With triethylamine In dichloromethane at 0℃; Inert atmosphere; | General Procedure of Derivatization General procedure: To a 50 mL round bottom flask with Et3N 12 mmol (1.21 g), CH3OH 1.2 equimolar (The amount of CH3OH depends on the number of acyl chloride groups contained in the substrate, 0.38 g CH3OH per acyl chloride group), CH2Cl2 10mL was added at 0°C. The acyl chloride 10 mmol was dissolved in CH2Cl2 5 mL and slowly added dropwise to the round bottom flask under N2 atmosphere through a syringe, the reaction mixture was maintained at -0°C, after completion of the reaction monitored by TLC, removed excess solvent, washed the residue with water 20 mL to obtain the crude product. The crude product was further purified by silica gel column chromatography (200-300 mesh), and n-hexane and ethyl acetate were used as eluents. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
83% | With sodium hydroxide In methanol; water at 50℃; for 0.25h; Microwave irradiation; | |
81% | With sodium hydroxide In methanol for 12h; Reflux; | |
80% | With sodium hydroxide In methanol for 12h; Reflux; |
79% | Stage #1: 1,3,5-tris-(methoxycarbonyl)benzene With water; sodium hydroxide In methanol for 18h; Stage #2: With hydrogenchloride In water | |
79% | Stage #1: 1,3,5-tris-(methoxycarbonyl)benzene With sodium hydroxide Stage #2: With hydrogenchloride | 5 The acid chloride (43) was prepared as follows. Trimethyl-1 ,3,5-benzenetricarboxylate (46) was converted to the mono-acid diester (47) according to literature procedures (Dimick, et al. "On the Meaning of Affinity: Cluster Glycoside Effects and Concanavalin A" J. Am. Chem. Soc. 1999, 121 , 10286- 10296), and compound 47 was refluxed in excess thionyl chloride to give acid chloride 43 (Scheme 5). |
79% | With water; sodium hydroxide In methanol at 20℃; for 22h; | Synthesis of 17 To a solution of Trimethyl 1,3,5-Benzenetricarboxylate (1.1 g, 4.36 mmol) in MeOH (100 mL) wasadded 1 M NaOH aq. (3.95 mL, 3.95 mmol). The solution was stirred for 22 h at rt. After removal ofthe solvent by evaporation, the mixture was washed with CH2Cl2. The aqueous layer was acidified with 6 M HCl to pH 2 and then extracted with AcOEt. The organic layer was dried over Na2SO4 andthe solution was concentrated by evaporation to give 17 (849 mg, 79%) as a white solid. |
78% | With sodium hydroxide In methanol for 12h; Reflux; | |
76% | With sodium hydroxide In methanol for 18h; | |
76% | With sodium hydroxide In methanol; water at 20℃; | |
75% | With sodium hydroxide In methanol; water at 20℃; for 18h; | |
73% | With sodium hydroxide In methanol; water for 16h; Reflux; | |
70% | With sodium hydroxide | |
70% | Stage #1: 1,3,5-tris-(methoxycarbonyl)benzene With sodium hydroxide In methanol; water for 36h; Stage #2: With sodium hydrogencarbonate In water at 50℃; for 2h; Stage #3: With hydrogenchloride In water | |
70% | With sodium hydroxide In methanol at 85℃; | |
69% | With sodium hydroxide In methanol for 12h; Heating; | |
60% | With sodium hydroxide In ethanol; water | |
55% | With sodium hydroxide In methanol | |
49% | With lithium hydroxide In tetrahydrofuran; water at 20℃; for 2.5h; | |
49.6% | With sodium hydroxide In methanol at 20℃; for 48h; | |
With hydrogenchloride; sodium hydroxide 1.) MeOH, rt., 1 h, 2.) pH=7-8, 16 h; Yield given. Multistep reaction; | ||
With sodium hydroxide In methanol; water | ||
With sodium hydroxide | ||
With water; sodium hydroxide | ||
With sodium hydroxide | ||
With sodium hydroxide In methanol for 12h; Reflux; | 1 Synthesis of product 1 3.7515 g of trimethyl 1,3,5-benzenetrihydroxy acid ester and 0.5798 g of NaOH were dissolved in 110 ml of methanol, and the temperature was slowly raised to reflux temperature for 12 hours, and the solvent was removed by rotary evaporation.The product was dissolved in dichloromethane and the product was extracted with saturated sodium bicarbonate. The extracted aqueous phase was washed twice with dichloromethane, then HCl was adjusted to pH = 1 and a precipitate was produced.The precipitate was washed with water until neutral and the product was dried in a vacuum oven to give product 1. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With hydrogen; acetic acid at 25℃; for 3.5h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
67% | With lithium aluminium deuteride In tetrahydrofuran for 10h; Heating; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With potassium <i>tert</i>-butylate; 4,4,5,5-tetramethyl-[1,3,2]-dioxaboralane; cobalt(II) iodide In acetonitrile at 30℃; for 12h; Glovebox; Inert atmosphere; regioselective reaction; | |
1: 90.2% 2: 6.3% | With C54H47NNiOP2 In toluene at 20℃; for 16h; Glovebox; Inert atmosphere; | |
1: 54% 2: 31% | In methanol; water at 75℃; for 0.5h; |
1: 29% 2: 48% | With tris-(dibenzylideneacetone)dipalladium(0); 2-{2-[(tert-butoxycarbonyl)amino]phenyl}buta-2,3-dien-1-yl ethyl carbonate In toluene at 120℃; Inert atmosphere; | |
1: 47% 2: 20% | With (((3-hydroxypropyl)carbonylcyclopentadienyl)cobalt)-η4-cyclooctadiene In methanol; water | |
With heterobimetallic heptamethylindenyl complex of Cr0 and Rh1 In cyclohexane at 50℃; for 1h; var. catalysts; | ||
1: 66 % Chromat. 2: 34 % Chromat. | With |
|
With (((3-hydroxypropyl)carbonylcyclopentadienyl)cobalt)-η4-cyclooctadiene In methanol; water other substituted alkynes; | ||
In benzene at 80℃; | ||
With ammonium tetrafluoroborate; [η5-C5H5RuCl(μ2SMe)2Ruη5-C5H5Cl] In methanol at 60℃; Yield given; Yields of byproduct given. Title compound not separated from byproducts; | ||
With [1,2-[C5(CH3)5]Rh}2B3H7] In tetrahydrofuran at 22℃; for 48h; Title compound not separated from byproducts; | ||
With phenylpropynoic acid methyl ester; 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl In toluene at 80℃; for 3h; Title compound not separated from byproducts; | ||
With N,N'-dicyclohexylethylenediimine; zinc(II) iodide; zinc In acetonitrile at 20℃; for 0.25h; Title compound not separated from byproducts; | ||
With [1,2-bis(4-methoxyphenylthio)ethane]cobalt dibromide; zinc(II) iodide; zinc In dichloromethane at 20℃; for 0.5h; Inert atmosphere; regioselective reaction; | ||
With di[(2,4-bis-tert-butyl-1-methoxy-3-neopentylcyclopentadienyl)dichlororuthenium(III)] In dichloromethane-d2 at 20℃; for 0.166667h; regioselective reaction; | ||
With cobalt(II) chloride; zinc(II) iodide; N,N''-bis(2,6-diisopropylphenyl)-N'-2,6-diisopropylphenylguanidine; zinc In acetonitrile at 23℃; for 2h; Inert atmosphere; regioselective reaction; | ||
With chloro-trimethyl-silane In butan-1-ol; benzene at 40℃; for 8h; regioselective reaction; | ||
With BF4(1-)*C18H27ClRu(1+); N-benzyl-N,N,N-triethylammonium chloride; 2,2-dimethyl-5,5-di(prop-2-ynyl)-1,3-dioxane-4,6-dione In dichloromethane at 20℃; | ||
With nido-[(η5-C5Me5Rh)2B6H10] In toluene at 70℃; for 24h; Inert atmosphere; Overall yield = 80 %Spectr.; | General procedure for catalytic process General procedure: Catalytic data for the alkyne cyclotrimerization was shown in Tables 1 and 2. All the alkynes were purchased from Sigma Aldrich and used as received. In a typical reaction, 1 (0.02 g) was dissolved in toluene (15 ml) and alkynes were added to that solution. The resulting reaction mixture was stirred at a temperature range 50-80 °C for 24-60 h (see Tables 1 and 2). The solvent was evaporated in vacuo; residue was extracted into hexane and passed through Celite. After removal of solvent from the filtrate, the residue was subjected to chromatographic work using silica gel TLC plates. Elution with hexane:CH2Cl2 yielded the corresponding benzene derivatives. Note that the formation of cyclotrimerized products and the ratios of the isomers were confirmed by 1H, and 13C NMR and mass spectrometry. The yield of the cyclotrimerized products was determined by 1H NMR spectroscopy employing a reference compound of known weight. | |
With CpCo(S<SUB>2</SUB>C<SUB>2</SUB>B<SUB>10</SUB>H<SUB>8</SUB>)(CH=CHCO<SUB>2</SUB>Me)<SUB>2</SUB> In toluene at 110℃; for 12h; Schlenk technique; Inert atmosphere; Overall yield = 59 %; | General procedures for the alkyne cyclotrimerization General procedure: The corresponding alkyne, the catalyst 1 and toluene (10 mL) were introduced in a schlenk tube and the reaction mixture was stirred at 70 °C or 110 °C for the indicated time (see Table 1 and Scheme 4). The reaction was monitored by regular sampling and analysis by gas chromatography. The resulting arenes were isolated by TLC and confirmed by NMR and mass spectroscopy. | |
With C8H6B2O8Re2(1-) In hexane at 30℃; for 2h; Overall yield = 85 %; regioselective reaction; | ||
With C30H42Br2N2Ni; zinc In acetonitrile at 50℃; for 9h; Schlenk technique; Inert atmosphere; Overall yield = 80 %; regioselective reaction; | ||
With C24H28CoNO5 In tetrahydrofuran-d8; water-d2 at 60℃; for 24h; Inert atmosphere; regioselective reaction; | ||
With [Rh(PhB(CH2PPh2)3-)(methyl propiolate)] In [D3]acetonitrile at 80℃; for 0.216667h; Inert atmosphere; Schlenk technique; regioselective reaction; | ||
With bis(1,3-dimesityl-1H-imidazol-2(3H)-ylidene)nickel(0) In benzene-d6 at 60℃; for 4h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 20.1% 2: 23% | With lithium aluminium tetrahydride In tetrahydrofuran at 1 - 30℃; for 0.166667h; | |
With lithium aluminium tetrahydride |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | In methanol at 4℃; for 24h; | |
98% | In methanol at 25℃; for 12h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72% | at 100℃; for 12h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
84% | With potassium carbonate In N,N-dimethyl-formamide at 40℃; for 14h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
25% | Stage #1: 2-(N,N-diphenylamino)thiophene With n-butyllithium In 1,4-dioxane; hexane at -15 - 0℃; Stage #2: 1,3,5-tris-(methoxycarbonyl)benzene With perchloric acid In 1,4-dioxane; hexane for 8h; Heating; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
31% | Stage #1: 4-(2-thiophenyl)morpholine With n-butyllithium In 1,4-dioxane; hexane at -15 - 0℃; Stage #2: 1,3,5-tris-(methoxycarbonyl)benzene With perchloric acid In 1,4-dioxane; hexane for 8h; Heating; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
76% | Stage #1: 2-propynyl 2,3:4,6-di-O-isopropylidene-α-D-mannopyranoside With n-butyllithium In tetrahydrofuran; hexane at 0℃; for 1h; Stage #2: 1,3,5-tris-(methoxycarbonyl)benzene In tetrahydrofuran; hexane at 20℃; for 24h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | With zirconium(IV) tert-butoxide; benzotriazol-1-ol In toluene at 100℃; for 2h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 64% 2: 25% | Stage #1: 1,3,5-tris-(methoxycarbonyl)benzene With sodium hydroxide In methanol for 18h; Heating; Stage #2: (S)-(-)-3,7-dimethyloctylamine With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In chloroform at 20℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 83% 2: 9 g | With water; sodium hydroxide In methanol for 8h; | 2 The trimethyl benzene-1,3,5-tricarboxylate (62 g, 246 mmol) was dissolved in MeOH (800 mL), aq. sodium hydroxide (221 mL, 221 mmol)-(1N) was slowly added. The suspension was stirred vigorously and slowly dissolved during 8 hours. The reaction was left stirred at room temperature for 18 hours, then the solvent was removed in vacuo. (1044) DCM (600 mL) was added to the solid and the organic phase was washed with sat. NaHCO3 (3×500 mL) 3 layers in the separation funnel-solution was filtered and solid on the funnel was rinsed with DCM. The LC-MS of the crude confirmed that MW was of the desired product (MW:238; 48.8 g; yield 83%). The LC-MS analysis of material from the organic layer showed a mixture of the desired product as well as over-hydrolyzed product (MW: 224; 9 g), and analysis of material from the aqueous layer showed start material. |
1: 33% 2: 7% | With silica gel In acetone at 200 - 220℃; for 2.3h; | |
With sodium hydroxide In methanol for 18h; Heating; Title compound not separated from byproducts; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | With N-Bromosuccinimide; sodium hydride In methanol at 120℃; for 0.5h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With oxygen In N,N-dimethyl-formamide |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With oxygen In N,N-dimethyl-formamide |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
65.4% | With oxygen In N,N-dimethyl-formamide at 50℃; for 24h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 72.1 % Chromat. 2: 21.6 % Chromat. | With carbon dioxide; oxygen at 80℃; for 15h; | |
1: 69.3 % Chromat. 2: 10.0 % Chromat. | With carbon dioxide; oxygen at 120℃; for 32h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: LiAlH4 / tetrahydrofuran / 24 h / Heating 2: 19.12 g / aq. HBr / toluene / 24 h / Heating | ||
Multi-step reaction with 2 steps 1: 99 percent / LiAlH4 / tetrahydrofuran / 6 h / Heating 2: 69 percent / HBr / H2O / 4 h / Heating | ||
Multi-step reaction with 2 steps 1: 95 percent / LAH / tetrahydrofuran / 5 h / Heating 2: 90 percent / aq. HBr / acetic acid / 1 h / 20 °C |
Multi-step reaction with 2 steps 1: LiAlH4 / tetrahydrofuran 2: PBr3 / diethyl ether | ||
Multi-step reaction with 2 steps 1: lithium aluminium hydride / tetrahydrofuran / Heating 2: 97 percent / 35 percent HBr / acetic acid | ||
Multi-step reaction with 2 steps 1: LiAlH4 / diethyl ether / 1 h / Heating 2: HBr / -30 - 20 °C | ||
Multi-step reaction with 2 steps 1: 100 percent / LiAlH4 / tetrahydrofuran / 1.5 h / Ambient temperature 2: 92 percent / 30percent HBr/AcOH / 1 h / Heating | ||
Multi-step reaction with 2 steps 1: 50 percent / LiAlH4 / tetrahydrofuran 2: PBr3 / diethyl ether | ||
Multi-step reaction with 2 steps 1: LiAlH4 / diethyl ether / 1 h / Heating 2: HBr / diethyl ether / 1.) -30 deg C, 5 min; 2.) room temp., 70 h | ||
Multi-step reaction with 2 steps 1: LiAlH4 / diethyl ether 2: PBr3 / diethyl ether | ||
Multi-step reaction with 2 steps 1: lithium aluminium tetrahydride / tetrahydrofuran / 16 h / 20 °C / Inert atmosphere 2: phosphorus tribromide / diethyl ether / 16 h | ||
Multi-step reaction with 2 steps 1: lithium aluminium tetrahydride / tetrahydrofuran / 24 h / Inert atmosphere; Reflux 2: hydrogen bromide / toluene / 24 h / Reflux | ||
Multi-step reaction with 2 steps 1: lithium aluminium tetrahydride / tetrahydrofuran / 18.5 h / 0 °C / Inert atmosphere; Reflux 2: phosphorus tribromide / diethyl ether / 24 h / 0 - 20 °C / Inert atmosphere |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 4 steps 1: LiAlH4 / tetrahydrofuran / 24 h / Heating 2: 19.12 g / aq. HBr / toluene / 24 h / Heating 3: 19 percent / Cs2CO3 / acetonitrile / 36 h / Heating 4: 50 percent / aq. HBr; phenol / 72 h / Heating |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1: LiAlH4 / tetrahydrofuran / 24 h / Heating 2: 19.12 g / aq. HBr / toluene / 24 h / Heating 3: 19 percent / Cs2CO3 / acetonitrile / 36 h / Heating |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: 69 percent / NaOH / methanol / 12 h / Heating 2: 91 percent / tetrahydrofuran / 96 h / Heating |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1: 69 percent / NaOH / methanol / 12 h / Heating 2: 91 percent / tetrahydrofuran / 96 h / Heating 3: 90 percent / diisopropylethylamine; benzotriazol-10-yloxy-tripyrrolidinophosphonium*PF6 / CH2Cl2; tetrahydrofuran / 12 h / 22 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: 49 percent / LiOH / tetrahydrofuran; H2O / 2.5 h / 20 °C 2: SOCl2; DMF / Heating | ||
Multi-step reaction with 2 steps 1: sodium hydroxide 2: thionyl chloride | ||
Multi-step reaction with 2 steps 1.1: sodium hydroxide / methanol; water / 36 h 1.2: 2 h / 50 °C 1.3: pH 1 2.1: thionyl chloride / N,N-dimethyl-formamide / 2 h / 90 °C / Inert atmosphere |
Multi-step reaction with 2 steps 1: sodium hydroxide / methanol; water / 16 h / Reflux 2: thionyl chloride; N,N-dimethyl-formamide / 2 h / 90 °C / Inert atmosphere | ||
Multi-step reaction with 2 steps 1: sodium hydroxide / methanol / 12 h / Reflux 2: thionyl chloride / 20 h / Reflux | ||
Multi-step reaction with 2 steps 1: sodium hydroxide / methanol / 85 °C 2: N,N-dimethyl-formamide; oxalyl dichloride / chloroform / 1.5 h |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1: 76 percent / 0.1 M aq. NaOH / methanol / 18 h 2: 88 percent / borane-methyl sulfide / tetrahydrofuran / 24 h / 27 °C 3: 93 percent / SOCl2 / 1 h / Heating | ||
Multi-step reaction with 3 steps 1: sodium hydroxide; water 2: dimethylsulfide borane complex 3: thionyl chloride / Reflux | ||
Multi-step reaction with 3 steps 1: sodium hydroxide / water; methanol / 18 h / 20 °C 2: dimethylsulfide borane complex / tetrahydrofuran / 24 h / 20 °C 3: thionyl chloride / 1.5 h / Inert atmosphere; Reflux |
Multi-step reaction with 2 steps 1: sodium tetrahydroborate; methanol / tetrahydrofuran / 0.5 h / Reflux 2: thionyl chloride / 1.5 h / Reflux | ||
Multi-step reaction with 2 steps 1: methanol; sodium tetrahydroborate / tetrahydrofuran / 0.5 h / 20 °C / Reflux 2: thionyl chloride / 1.5 h / Reflux |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 6 steps 1: 76 percent / 0.1 M aq. NaOH / methanol / 18 h 2: 88 percent / borane-methyl sulfide / tetrahydrofuran / 24 h / 27 °C 3: 93 percent / SOCl2 / 1 h / Heating 4: 97 percent / NaN3 / acetone; H2O / 16 h / Heating 5: 99 percent / 1 M aq. KOH / methanol / 1 h / Heating 6: 100 percent / SOCl2 / 1 h / Heating | ||
Multi-step reaction with 6 steps 1: sodium hydroxide; water 2: dimethylsulfide borane complex 3: thionyl chloride / Reflux 4: sodium azide 5: sodium hydroxide; water 6: thionyl chloride / Reflux |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 4 steps 1: 76 percent / 0.1 M aq. NaOH / methanol / 18 h 2: 88 percent / borane-methyl sulfide / tetrahydrofuran / 24 h / 27 °C 3: 93 percent / SOCl2 / 1 h / Heating 4: 97 percent / NaN3 / acetone; H2O / 16 h / Heating | ||
Multi-step reaction with 4 steps 1: sodium hydroxide; water 2: dimethylsulfide borane complex 3: thionyl chloride / Reflux 4: sodium azide | ||
Multi-step reaction with 4 steps 1: sodium hydroxide / water; methanol / 18 h / 20 °C 2: dimethylsulfide borane complex / tetrahydrofuran / 24 h / 20 °C 3: thionyl chloride / 1.5 h / Inert atmosphere; Reflux 4: sodium azide / water; acetone / Reflux |
Multi-step reaction with 3 steps 1: sodium tetrahydroborate; methanol / tetrahydrofuran / 0.5 h / Reflux 2: thionyl chloride / 1.5 h / Reflux 3: sodium azide / water; acetonitrile / 16 h / Reflux | ||
Multi-step reaction with 3 steps 1: methanol; sodium tetrahydroborate / tetrahydrofuran / 0.5 h / 20 °C / Reflux 2: thionyl chloride / 1.5 h / Reflux 3: sodium azide / water; acetone / 16 h / Reflux |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 5 steps 1: 76 percent / 0.1 M aq. NaOH / methanol / 18 h 2: 88 percent / borane-methyl sulfide / tetrahydrofuran / 24 h / 27 °C 3: 93 percent / SOCl2 / 1 h / Heating 4: 97 percent / NaN3 / acetone; H2O / 16 h / Heating 5: 99 percent / 1 M aq. KOH / methanol / 1 h / Heating | ||
Multi-step reaction with 5 steps 1: sodium hydroxide; water 2: dimethylsulfide borane complex 3: thionyl chloride / Reflux 4: sodium azide 5: sodium hydroxide; water | ||
Multi-step reaction with 4 steps 1: sodium tetrahydroborate; methanol / tetrahydrofuran / 0.5 h / Reflux 2: thionyl chloride / 1.5 h / Reflux 3: sodium azide / water; acetonitrile / 16 h / Reflux 4: water; lithium hydroxide / methanol; tetrahydrofuran / 48 h / 20 °C |
Multi-step reaction with 4 steps 1: methanol; sodium tetrahydroborate / tetrahydrofuran / 0.5 h / 20 °C / Reflux 2: thionyl chloride / 1.5 h / Reflux 3: sodium azide / water; acetone / 16 h / Reflux 4: lithium hydroxide; water / tetrahydrofuran; methanol / 48 h / 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 8 steps 1: 76 percent / 0.1 M aq. NaOH / methanol / 18 h 2: 88 percent / borane-methyl sulfide / tetrahydrofuran / 24 h / 27 °C 3: 93 percent / SOCl2 / 1 h / Heating 4: 97 percent / NaN3 / acetone; H2O / 16 h / Heating 5: 99 percent / 1 M aq. KOH / methanol / 1 h / Heating 6: 100 percent / SOCl2 / 1 h / Heating 7: 53 percent / Et3N / tetrahydrofuran / 16 h / 25 °C 8: 79 percent / 0.1 M NaOMe / 2 h / 25 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 8 steps 1: 76 percent / 0.1 M aq. NaOH / methanol / 18 h 2: 88 percent / borane-methyl sulfide / tetrahydrofuran / 24 h / 27 °C 3: 93 percent / SOCl2 / 1 h / Heating 4: 97 percent / NaN3 / acetone; H2O / 16 h / Heating 5: 99 percent / 1 M aq. KOH / methanol / 1 h / Heating 6: 100 percent / SOCl2 / 1 h / Heating 7: 53 percent / Et3N / tetrahydrofuran / 16 h / 25 °C 8: H2 / Pd/C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 7 steps 1: 76 percent / 0.1 M aq. NaOH / methanol / 18 h 2: 88 percent / borane-methyl sulfide / tetrahydrofuran / 24 h / 27 °C 3: 93 percent / SOCl2 / 1 h / Heating 4: 97 percent / NaN3 / acetone; H2O / 16 h / Heating 5: 99 percent / 1 M aq. KOH / methanol / 1 h / Heating 6: 100 percent / SOCl2 / 1 h / Heating 7: 53 percent / Et3N / tetrahydrofuran / 16 h / 25 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: 70 percent / NaOH 2: 49 percent / 1 M lithium triethylborohydride / tetrahydrofuran | ||
Multi-step reaction with 2 steps 1: 23 percent / LiAlH4 / tetrahydrofuran / 0.17 h / 1 - 30 °C 2: KOH / methanol | ||
Multi-step reaction with 2 steps 1: 1.) 0.95 N sodium hydroxide, 2.) 5 percent HCl / 1.) MeOH, rt., 1 h, 2.) pH=7-8, 16 h 2: 71 percent / 1.0 M lithium triethylborohydride / tetrahydrofuran / Ambient temperature |
Multi-step reaction with 2 steps 1: lithium tetrahydridoborate / tetrahydrofuran / 3 h / 80 °C 2: sodium hydroxide / methanol; water monomer / 16 h / 25 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1: 50 percent / LiAlH4 / tetrahydrofuran 2: PBr3 / diethyl ether 3: 1.) thiourea |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: 95 percent / H2, acetic acid / platinum oxide / 3.5 h / 25 °C / 1034.3 - 2585.7 Torr 2: 57 percent / lithium aluminum hydride / diethyl ether / 16 h / Heating |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1: 95 percent / H2, acetic acid / platinum oxide / 3.5 h / 25 °C / 1034.3 - 2585.7 Torr 2: 57 percent / lithium aluminum hydride / diethyl ether / 16 h / Heating 3: 70 percent / dimethyl sulfoxide, oxalyl chloride / CH2Cl2 / 2.25 h / -55 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 4 steps 1: 95 percent / H2, acetic acid / platinum oxide / 3.5 h / 25 °C / 1034.3 - 2585.7 Torr 2: 57 percent / lithium aluminum hydride / diethyl ether / 16 h / Heating 3: 70 percent / dimethyl sulfoxide, oxalyl chloride / CH2Cl2 / 2.25 h / -55 °C 4: 99 percent / diethyl ether; tetrahydrofuran / 96 h / 25 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 4 steps 1: 95 percent / H2, acetic acid / platinum oxide / 3.5 h / 25 °C / 1034.3 - 2585.7 Torr 2: 57 percent / lithium aluminum hydride / diethyl ether / 16 h / Heating 3: 70 percent / dimethyl sulfoxide, oxalyl chloride / CH2Cl2 / 2.25 h / -55 °C 4: 88 percent / diethyl ether; tetrahydrofuran / 17 h / 25 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 5 steps 1: 95 percent / H2, acetic acid / platinum oxide / 3.5 h / 25 °C / 1034.3 - 2585.7 Torr 2: 57 percent / lithium aluminum hydride / diethyl ether / 16 h / Heating 3: 70 percent / dimethyl sulfoxide, oxalyl chloride / CH2Cl2 / 2.25 h / -55 °C 4: 99 percent / diethyl ether; tetrahydrofuran / 96 h / 25 °C 5: manganese dioxide / CHCl3 / 11.5 h / 25 °C | ||
Multi-step reaction with 4 steps 1: 95 percent / H2, acetic acid / platinum oxide / 3.5 h / 25 °C / 1034.3 - 2585.7 Torr 2: 57 percent / lithium aluminum hydride / diethyl ether / 16 h / Heating 3: 70 percent / dimethyl sulfoxide, oxalyl chloride / CH2Cl2 / 2.25 h / -55 °C 4: acetic acid / ethanol / 18.5 h / Heating |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 4 steps 1: 95 percent / H2, acetic acid / platinum oxide / 3.5 h / 25 °C / 1034.3 - 2585.7 Torr 2: 57 percent / lithium aluminum hydride / diethyl ether / 16 h / Heating 3: 70 percent / dimethyl sulfoxide, oxalyl chloride / CH2Cl2 / 2.25 h / -55 °C 4: diethyl ether; tetrahydrofuran / 96 h / 25 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 4 steps 1: 95 percent / H2, acetic acid / platinum oxide / 3.5 h / 25 °C / 1034.3 - 2585.7 Torr 2: 57 percent / lithium aluminum hydride / diethyl ether / 16 h / Heating 3: 70 percent / dimethyl sulfoxide, oxalyl chloride / CH2Cl2 / 2.25 h / -55 °C 4: diethyl ether; tetrahydrofuran / 17 h / 25 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 4 steps 1: 95 percent / H2, acetic acid / platinum oxide / 3.5 h / 25 °C / 1034.3 - 2585.7 Torr 2: 57 percent / lithium aluminum hydride / diethyl ether / 16 h / Heating 3: 70 percent / dimethyl sulfoxide, oxalyl chloride / CH2Cl2 / 2.25 h / -55 °C 4: hydrazine / tetrahydrofuran; diethyl ether / 19 h / 25 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 4 steps 1: 95 percent / H2, acetic acid / platinum oxide / 3.5 h / 25 °C / 1034.3 - 2585.7 Torr 2: 57 percent / lithium aluminum hydride / diethyl ether / 16 h / Heating 3: 70 percent / dimethyl sulfoxide, oxalyl chloride / CH2Cl2 / 2.25 h / -55 °C 4: 100 percent / tetrahydrofuran; diethyl ether / 16 h / 25 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | In methanol Reflux; | |
91% | With sulfuric acid In methanol Reflux; | |
Multi-step reaction with 2 steps 1: 71 percent / thionyl chloride, pyridine / 336 h / Heating 2: 64.5 percent / triethylamine / 2 h / ice bath |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | In methanol; chloroform | Synthesis of 1,3,5-Tris(methoxycarbonyl)benzene (S. M. Dimick, S. C. Powell, S. A. McMahon, D. N. Moothoo, J. H. Naismith. E. J. Toone, J. Am. Chem. Soc. 1999. 121 10286-10296) Synthesis of 1,3,5-Tris(methoxycarbonyl)benzene (S. M. Dimick, S. C. Powell, S. A. McMahon, D. N. Moothoo, J. H. Naismith. E. J. Toone, J. Am. Chem. Soc. 1999. 121 10286-10296) In a flask equipped with a condenser and a drying tube 1,3,5-benzenetricarboxylic acid 49(22.12 g, 0.1 mol) was suspended in methanol (250 ml), concentrated sulphuric acid (25 ml) was added, and the mixture was refluxed over night. After cooling to 0° C. the white precipitate was filtered off, washed with cold water, dissolved in CHCl3, and dried over MgSO4. Removal of the solvent gave the desired product (22.05 g, 87%) as a white powder; mp 142-144° C. (lit. 144-144.5° C.); 1H NMR (300 MHz, CDCl3) δ3.99 (s, 3H, CH3), 8.85 (s, 1H, aromat. H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With n-butyllithium In tetrahydrofuran; hexane | 15 2-[3,5-bis-(Methoxycarbonyl)-benzoyl]-6-[(1E)-(3RS)-3-hydroxy-1-undecenyl]-pyridine EXAMPLE 15 2-[3,5-bis-(Methoxycarbonyl)-benzoyl]-6-[(1E)-(3RS)-3-hydroxy-1-undecenyl]-pyridine Under the conditions of example 1B, 1 g of 2-bromo-6-[(1E)(3RS)-3-hydroxy-1-undecenyl)-pyridine in 10 ml of tetrahydrofuran is mixed with 4.26 ml of n-butyllithium (1.6 molar in hexane) and 807 mg of 1,3,5-benzenetricarboxylic acid trimethylester in 6 ml of tetrahydrofuran, worked up and chromatographed on silica gel with hexane/ethyl acetate=95/5 to 75/25. 203 mg of oily crude product is obtained, which is subjected to complete purification of the high-pressure liquid chromatography on silanized silica gel (RP 18 material) with methanol/H2 O=9:1. 74 mg of the title compound is thus obtained as colorless oil. IR (Film): 3560-3160, 2920, 2850, 1730, 1670, 1590, 1450, 1345, 875, 850, 820 cm-1. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
81.2% | With hydrazine hydrate; In ethanol; at 80.0℃; for 24.0h; | In a 250mL round-bottomed flask, 100ml of ethanol and 1,3,5-tricarboxylic acid tricresyl ester (1.39g, 5mmol) were added, and then 8ml of hydrazine hydrate was added dropwise, and the reaction was stirred and refluxed at 80C for 24h. After the completion of the reaction, the reaction solution was cooled to room temperature, and a large amount of solid was precipitated and filtered under reduced pressure. The filter cake was washed 3 times with ethanol and dried to obtain pure target compound (3) (1,2,3,5-trihydrazide). Yield 81.2%, |
With hydrazine hydrate; In ethanol; for 8.0h;Reflux; | Synthesis of intermediate product: Weighing Trimethyl benzenetricarboxylate (5.0 g, 0.02 mol), hydrazine hydrate (85%, 3.79 g, 0.065 mol), Add to a 250 mL flask containing 150 mL of ethanol, reflux under magnetic stirring for 8 h, and disperse heat into a beaker containing a large amount of water. Filtration and recrystallization from ethanol, drying to obtain an intermediate product, to be used; Synthesis of Al3+ probe compounds: The intermediate product (5.0 g, 0.02 mol), salicylaldehyde (7.3 g, 0.06 mol) was weighed and added to a 250 mL flask containing 100 mL of DMF.The reaction was stirred magnetically at 90 C for 8 h, and the heat was dispersed into a beaker containing a large amount of water. Filtered and washed three times with ethanol at 0.06 MPa, Drying under vacuum at 60 C gave a white powdery pure Al3+ probe compound. The calculated yield was 96%. | |
With ethanol; hydrazine hydrate; at 20.0℃; for 8.0h; | (1) The trimesic acidTrimethyl ester (5.0g, 0.02mol) and hydrazine hydrate (85%, 3.79g, 0.065mol) were added to a 250mL flask containing 150mL of ethanol, refluxed for 8h under magnetic stirring at room temperature, and dispersed until it was heated to a large amount of water In the beaker, suction filtered and recrystallized with ethanol,After drying, the product trimesic hydrazide is obtained; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
79% | Stage #1: 1,3,5-tris-(methoxycarbonyl)benzene With sodium hydroxide In methanol; water monomer at 20℃; for 15h; Stage #2: With hydrogenchloride; water monomer chemoselective reaction; | To a suspension of 1,3,5-benzenetricarboxylic acid trimethyl ester (1) (2.2 g, 8.8 mmol) in MeOH (100 mL), aq NaOH (22.8 mL, 0.8 M, 2.07 equiv) was added. The resulting cloudy mixture was stirred vigorously (rt) and slowly formed a solution over 5 h. After 15 h, MeOH was removed in vacuo. H2O (50 mL) was added and the solution acidified (pH 2.0) with 6 M HCl, yielding a white dispersion. The organic material was extracted with EtOAc (50 mL). The solvent was removed to give 2 (impure with 7-8% of 1,3,5-benzenetricarboxylic acid dimethyl ester, according to NMR) as a white powder. Crystallization from EtOAc provided pure monoester 2 (1.6 g, 79%): mp 220-221 °C; 1H NMR (200 MHz, CD3OD/CDCl3 1:1) δ = 3.95 (s, 3H), 8.81 [d, 4J(H,H) = 1.6 Hz, 2H], 8.83 [t, 4J(H,H) = 1.6 Hz, 1H] ppm. 13C NMR (50 MHz, CD3OD/CDCl3 1:1) δ = 53.01 (CH3), 131.8 (Ar), 132.6 [2C, (Ar)], 134.9 [2C, (ipso Ar)], 135.4 (ipso Ar), 166.4 (CO), 167.4 [2C, (CO)] ppm. |
78% | With water monomer; sodium hydroxide In methanol for 3h; Reflux; Inert atmosphere; | 7.3 Step 3 NaOH (1.665 g, 41.6 mmol) was added to a stirred solution of trimethyl benzene-1,3,5-tricarboxylate compound 53 (5 g, 19.82 mmol) in MeOH (66.1 mL) and water (13.22 mL). The reaction mixture was refuxed under Ar for 3 h. Lots of white precipitate had formed. The solution was cooled to rt and was diluted with H2O until all solids were dissolved. The mixture was acidified to pH 2-3 with aqueous 5 N HCl, extracted with EtOAc (3×), dried over Na2SO4, filtered and concentrated. The crude product was dissolved in hot EtOAc (50 mL) and was cooled to rt slowly. The precipitate was filtered (precipitate was by-product and not product). The mother liquor was concentrated to obtain compound 54 as a white solid (3.45 g, 78% yield). 1H NMR (400 MHz, DMSO-d6): δ 13.62 (bs, 2H), 8.65 (s, 3H), 3.93 (s, 3H). LCMS=3.209 min (8 min method). Mass observed (ESI+): 244.90 (M+H). |
78% | With water monomer; sodium hydroxide In methanol for 3h; Inert atmosphere; Reflux; |
72% | With sodium hydroxide In methanol at 85℃; for 21h; | |
72% | With sodium hydroxide In methanol; water monomer | |
65% | With sodium hydroxide In methanol for 12h; Reflux; | |
62% | Stage #1: 1,3,5-tris-(methoxycarbonyl)benzene With sodium hydroxide In methanol; water monomer at 20℃; Stage #2: With hydrogenchloride In water monomer | 2 Methyl 1,3,5-benzenetricarboxylate S2. Trimethyl 1,3,5-benzenetricarboxylate (22.0 g, 87.2 mmol) was dissolved in MeOH (700 mL). NaOH aq (6.97 g, 174.3 mmol NaOH in 100 mL water) was added dropwise with stirring. Stirring was continued at room temperature overnight, then the solvent was removed and the crude white solid was dissolved in saturated NaHC03 aq (600 mL). The pH of the solution was adjusted to 5.5 by adding HC1 aq (1 M), and the aqueous solution was extracted with EtOAc (250 mL χ 3) to remove dimethyl 1,3,5-benzenetricarboxylate. The pH of the aqueous solution was then further adjusted to 4.4 and extracted with EtOAc (250 mL χ 3). The organic phases were combined, washed with brine, dried over MgS04 and concentrated in vacuo to afford S2 as a white solid (Rf = 0.5, EtOAc : MeOH : H20 = 80:20: 1). Yield 62 % (12.2 g, 54.5 mmol). NMR (400MHz, (CD3)2CO) δ = 8.86 (t, J= 1.7 Hz, 1H), 8.82 (d, J = 1.7, 2H), 3.98 (s, 3H). 13C NMR (100MHz, (CD3)2CO) δ = 166.1, 165.9, 135.3, 135.0, 132.8, 132.8, 132.4, 53.1. This material was used without further purification. |
62% | Stage #1: 1,3,5-tris-(methoxycarbonyl)benzene With water monomer; sodium hydroxide In methanol at 20℃; Stage #2: With hydrogenchloride In water monomer | 2 Methyl 1,3,5-benzenetricarboxylate S2. Trimethyl 1,3,5-benzenetricarboxylate (22.0 g, 87.2 mmol) was dissolved in MeOH (700 mL). NaOH aq (6.97 g, 174.3 mmol NaOH in 100 mL water) was added dropwise with stirring. Stirring was continued at room temperature overnight, then the solvent was removed and the crude white solid was dissolved in saturated NaHCO3 aq (600 mL). The pH of the solution was adjusted to 5.5 by adding HCl aq (1 M), and the aqueous solution was extracted with EtOAc (250 mL×3) to remove dimethyl 1,3,5-benzenetricarboxylate. The pH of the aqueous solution was then further adjusted to 4.4 and extracted with EtOAc (250 mL×3). The organic phases were combined, washed with brine, dried over MgSO4 and concentrated in vacuo to afford S2 as a white solid (Rf=0.5, EtOAc:MeOH:H2O=80:20:1). Yield 62% (12.2 g, 54.5 mmol). 1H NMR (400 MHz, (CD3)2CO) δ=8.86 (t, J=1.7 Hz, 1H), 8.82 (d, J=1.7, 2H), 3.98 (s, 3H). 13C NMR (100 MHz, (CD3)2CO) δ=166.1, 165.9, 135.3, 135.0, 132.8, 132.8, 132.4, 53.1. This material was used without further purification. |
60% | With sodium hydroxide In methanol at 85℃; for 24h; | |
40% | With sodium hydroxide In methanol at 85℃; for 12h; | |
With methanol; potassium hydroxide at 0 - 25℃; for 2h; | 1.1.b Will be bothTrimethyl trimellitateSoluble in methanol, trimethyl t-trimellitate and methanol to the mass ratio of 1:25,The molar ratio of trimethyl terephthalate to KOH was 1: 2,0 stirring 2h,Natural warming to 25 ,(4 × 10ml), dried over MgSO4, and the chloroform was removed by filtration to give 3,5-dichlorophenol, which was washed with water and concentrated in water. Dibutyric acid-1-benzoate.. | |
With methanol; sodium hydroxide for 12h; Reflux; | ||
With water monomer; sodium hydroxide In methanol at 20℃; | 1.3.5-Benzene tricarboxylate monomethyl ester (9p). 1.8M Aqueous NaOH (9.1 mL, 16.4 mmoles, ~2 eqs.) was added dropwise to a vigorously stirred suspension of 1.3.5-benzene tricarboxylate trimethyl ester (2.0 g, 8.0 mmoles, 1 eq.) in MeOH (64 mL) at r.t.. Stirring at r.t. was continued for 5 hrs, obtaining a clear solution. After solvent evaporation at reduced pressure, water (25 mL) was added and the pH was brought to2.0 by dropwise addition of aqueous 6N HC1. The resulting suspension was extracted with EtOAc (2 x 25 mL). After washing with water (2 x 10 mL) and brine (2 x 10 mL), the combined organic phase was concentrated at reduced pressure. The crude 1,3,5-benzene tricarboxylate monomethyl ester 9p (1.5 g) was used in the next reaction step without further purification. MS (ESI+): m/z 225.22 [M+H+] Calculated MS, CioHsOe: 224.17. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
46% | With potassium hydrogenfluoride; trifluorormethanesulfonic acid; (trifluoromethyl)trimethylsilane In N,N-dimethyl-formamide; acetonitrile at 20℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium hydride In tetrahydrofuran at 60℃; for 24h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1: sodium hydroxide / methanol 2: dimethyl sulfide borane / tetrahydrofuran / 20 °C 3: pyridinium chlorochromate / dichloromethane | ||
Multi-step reaction with 2 steps 1: lithium borohydride / tetrahydrofuran / 0.5 h / Inert atmosphere; Reflux 2: pyridinium chlorochromate / dichloromethane / 15 h / Reflux | ||
Multi-step reaction with 2 steps 1: lithium borohydride / tetrahydrofuran / 0 °C / Inert atmosphere; Reflux 2: dicyclohexyl-carbodiimide / dichloromethane / Inert atmosphere; Reflux |
Multi-step reaction with 2 steps 1: sodium tetrahydroborate / tetrahydrofuran / 0.5 h / Inert atmosphere; Reflux 2: pyridinium chlorochromate / dichloromethane / 24 h / Reflux |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 5 steps 1.1: lithium borohydride / tetrahydrofuran / 0.5 h / Inert atmosphere; Reflux 2.1: pyridinium chlorochromate / dichloromethane / 15 h / Reflux 3.1: trifluoroacetic acid / dichloromethane / 20 °C / Inert atmosphere 4.1: boron trifluoride diethyl etherate / chloroform / 3 h / 20 °C / Molecular sieve; Inert atmosphere; Darkness 4.2: 0.5 h / 20 °C / Molecular sieve; Inert atmosphere; Darkness 4.3: 0.5 h / 20 °C / Molecular sieve; Darkness; Inert atmosphere 5.1: 48 h / 85 °C / Sealed tube |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1: lithium borohydride / tetrahydrofuran / 0.5 h / Inert atmosphere; Reflux 2: pyridinium chlorochromate / dichloromethane / 15 h / Reflux 3: trifluoroacetic acid / dichloromethane / 20 °C / Inert atmosphere |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1: lithium borohydride / tetrahydrofuran / 0.5 h / Inert atmosphere; Reflux 2: pyridinium chlorochromate / dichloromethane / 15 h / Reflux 3: trifluoroacetic acid / dichloromethane / 20 °C / Inert atmosphere |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 4 steps 1.1: lithium borohydride / tetrahydrofuran / 0.5 h / Inert atmosphere; Reflux 2.1: pyridinium chlorochromate / dichloromethane / 15 h / Reflux 3.1: trifluoroacetic acid / dichloromethane / 20 °C / Inert atmosphere 4.1: boron trifluoride diethyl etherate / chloroform / 3 h / 20 °C / Molecular sieve; Inert atmosphere; Darkness 4.2: 0.5 h / 20 °C / Molecular sieve; Inert atmosphere; Darkness 4.3: 0.5 h / 20 °C / Molecular sieve; Darkness; Inert atmosphere |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 5 steps 1.1: lithium borohydride / tetrahydrofuran / 0.5 h / Inert atmosphere; Reflux 2.1: pyridinium chlorochromate / dichloromethane / 15 h / Reflux 3.1: trifluoroacetic acid / dichloromethane / 20 °C / Inert atmosphere 4.1: boron trifluoride diethyl etherate / chloroform / 3 h / 20 °C / Molecular sieve; Inert atmosphere; Darkness 4.2: 0.5 h / 20 °C / Molecular sieve; Inert atmosphere; Darkness 4.3: 0.5 h / 20 °C / Molecular sieve; Darkness; Inert atmosphere 5.1: potassium hydroxide / tetrahydrofuran; ethanol; water / Reflux 5.2: pH 2 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | Stage #1: 1-bromo-4-methoxy-benzene With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 1h; Inert atmosphere; Stage #2: 1,3,5-tris-(methoxycarbonyl)benzene In tetrahydrofuran; hexane at -78 - 20℃; for 19h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | In tetrahydrofuran at -78 - 20℃; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 31% 2: 15% | Stage #1: vinyl magnesium bromide With CuN(1-)*Cu(1+) In tetrahydrofuran at -50 - -45℃; for 1h; Inert atmosphere; Stage #2: 1,3,5-tris-(methoxycarbonyl)benzene In tetrahydrofuran for 18h; Inert atmosphere; Cooling with ice; | 4.1.1 1-[4,6-Di-(pent-4-enoyl)phenyl]pent-4-en-1-one (7) A magnetic stirrer bar and CuCN (2.9 g, 0.387 mmol) were placed in a 3-neck round bottom flask, flame dried briefly under a stream of argon, allowed to cool to room temperature, suspended in 10 mL of THF, cooled to -50 °C, treated with a freshly prepared solution of vinylmagnesium bromide in THF (1.3 M, 680 mL, 884 mmol) and stirred for 1 h maintaining the temperature between -45 and -50 °C. The resulting mixture was treated with a solution of trimethyl 1,3,5-benzene tricarboxylate (6, 8.13 g, 32.23 mmol) in THF (30 mL) over 15 min. The cooling bath was replaced with an ice bath and stirring was continued for 18 h. The dark slurry was poured onto an ice-chilled, rapidly stirred biphasic solution of 1 M NaH2PO4 (800 mL) and Et2O (800 mL). The phases were separated and the aqueous phase was extracted with Et2O (3×800 mL). The pooled extracts were washed with 1 M NaHCO3 (800 mL) and brine (800 mL), dried (MgSO4), filtered and the volatiles were evaporated to give a residue, which was purified by chromatography over silica gel eluting with 20% ethyl acetate in dichloromethane. First to elute was 1-[4,6-di-(pent-4-enoyl) phenyl]pent-4-en-1-one 7 as yellow oil (1.618 g, 31%): Rf 0.36 (15% ethyl acetate in hexane). 1H NMR (400 MHz, CDCl3) δ 2.51 (q, J1=7.0, J2=7.0 Hz, 6H), 3.15 (t, J=7.3 Hz, 6H), 5.03 (dd, J1=1.4, J2=17.1 Hz, 3H), 5.13 (d, J=10.2 Hz, 3H), 5.85 (m, 3H), 8.70 (s, 3H). 13C NMR (100 MHz, acetone-d6) δ 27.7, 37.9, 115.5, 130.9, 136.6, 137.5, 197.7. HRMS (ESI) calcd for C21H25O3 [M+H+] 325.1798, found 325.1808. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
55% | Stage #1: 2,2’-dibromodiphenylmethane With magnesium In tetrahydrofuran at 20℃; for 12h; Inert atmosphere; Reflux; Stage #2: 1,3,5-tris-(methoxycarbonyl)benzene In tetrahydrofuran at 20℃; for 4h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | In methanol at 40℃; for 72h; | 4.5. Synthesis of compound 6 4-Nitro-N-(2-aminoethyl)-1,8-naphthalimide (0.855 g, 0.003 mol) was reacted with trimethyl-1,3,5-benzenetricarboxylate (0.05 g. 0.001 mol) in 30 ml of methanol for 72 h at 40 °C. After that the methanol solution was evaporated and 100 ml of water were added. The solid precipitate was filtered off, washed with methanol and water, and dried in vacuum at 40 °C. Yield: 96%. IR (cm-1): 3080, 2935, 2876, 1701, 1674, 1654, 1622, 1522, 1435, 1350, 1327, 1231, 765, 760, 1H NMR (DMSO-d6, ppm): δ 3.92 (m, 6H, (OC)2NCH2CH2NHCO), 4.29 (t, 6H, (OC)2NCH2CH2NHCO), 6.76 (d, J=8.8 Hz, 3H), 7.36 (d, J=7.89 Hz, 3H), 8.22 (d, J=8.8 Hz, 3H), 8.32 (d, J=7.8 Hz, 3H), 8.59 (m, 3H+3NH); 13C NMR (DMSO-d6, ppm): 167.3, 164.6, 163.9, 145.1, 140.2, 131.4, 130.2, 128.6, 128.0, 127.1, 125.3, 114.5, 103.8, 103.8, 99.2, 33.1, 28.2; API-ES-MS (positive) m/z: calcd: 1011.2; found: 1012.5 ([M+H]+), 1013.4 ([M+2H]+); Analysis: C51H33N9O15 (1011.2 g mol-1) Calculated (%): C 60.52, H 3.26, N 12.46; Found (%): C 60.39, H 3.31, N 12.38. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: methanol; potassium hydroxide / 2 h / 0 - 25 °C 2: toluene / 12 h / 120 °C | ||
Multi-step reaction with 4 steps 1: sodium hydroxide / methanol / 12 h / Reflux 2: thionyl chloride / 20 h / Reflux 3: triethylamine / dichloromethane / 18 h / 20 °C 4: potassium hydroxide / methanol; water / 2 h / Reflux | ||
Multi-step reaction with 4 steps 1: sodium hydroxide / methanol / 85 °C 2: N,N-dimethyl-formamide; oxalyl dichloride / chloroform / 1.5 h 3: triethylamine / dichloromethane / 24 h / 0 - 20 °C / Inert atmosphere 4: sodium hydroxide / methanol / 24 h / 85 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | In methanol at 0 - 20℃; for 24.5h; Inert atmosphere; | 4.3.1. N,N′,N′′-tris(2-aminoethyl)benzene-1,3,5-tricarboxamide The title compound was prepared by a method similar tothat reported by Xu et al. (17) Under an argon atmosphere,ethylenediamine (20 mL) was added to a flask. Trimethylbenzene-1,3,5-tricarboxylate (0.51 g, 2.02 mmol) was dissolvedin methanol (20 mL) and added dropwise to thesolution of ethylenediamine (EDA) under an argon atmosphereat 0 °C. The solution was stirred at 0 °C for 30 minand then at room temperature for 24 h. The excess ethylenediaminewas removed in vacuo, and the residue wasdissolved in a mixture of toluene/methanol (10:1) and thesolvent was again removed under vacuum to remove theresidual ethylenediamine. This process was repeated threetimes and the product was obtained as a sticky yellowsolid. Yield: 0.67 g (98%); δH(400 MHz, DMSO-d6) δ = 8.61(t, J = 5.6 Hz, 3H, H4), 8.39 (s, 3H, H5), 3.29 (q, J = 6.2 Hz,overlapping with water peak, H3), 2.70 (t, J = 6.5 Hz, 6H, H2);δC (101 MHz, DMSO-d6) δ = 165.7, 135.1, 128.4, 43.2, 41.3;m/z (ESI+) 337.1989 ([M + H]+, calculated for C15H25N6O3+337.1983; νmax (ATR, cm-1) 3278m, 3064m, 2932m, 2870m,1639 s, 1589m, 1534s, 1430m, 1387m, 1287s, 1186m,1108m, 1071m, 1035m, 913m, 852m, 821m, 703s. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
43% | With tridodecylmethylammonium chloride In hexane; toluene at 69℃; for 3h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
14% | Stage #1: 1,3,5-tris-(methoxycarbonyl)benzene; 1-[4-(1,2,2-triphenylethenyl)phenyl]ethan-1-one With sodium hydride In tetrahydrofuran at 60℃; for 24h; Inert atmosphere; Stage #2: boron trifluoride diethyl etherate In dichloromethane for 2h; Reflux; Inert atmosphere; | 3 2.2.1. 2,2-Difluoro-6-phenyl-4-(4-(1,2,2-triphenylvinyl)phenyl)-2H-1,3,2-dioxaborinin-1-ium-2-uide (TPEB) General procedure: 1-(4-(1,2,2-triphenylvinyl)phenyl)ethanone (2 g, 5 mmol) andmethyl benzenecarboxylate (0.82 g, 6 mmol) were dissolved in dryTHF (50 mL) under an atmosphere of nitrogen. Then, NaH (0.4 g,10 mmol) was added. The mixture was stirred at 60° C for 24 h,followed by poured into ice water (300 mL). HCl (6 M, 10 mL) wasadded to neutralize excess NaH. The mixture was extracted withCH2Cl2 for three times, and the organic phase was combined anddried over magnesium sulfate. After removal of solvent, the residuewas used directly in the next step without purification. Then, thesolution of the ligand of the b-diketone ligand in dry dichloromethane(50 mL) was heated to reflux under an atmosphere ofnitrogen, and excess BF3Et2O (1.35 mL) was added. The mixturewas refluxed for 2 h. After the solvent was removed, the residuewas purified by column chromatography (silica) using petroleumether/CH2Cl2 (v/v 3/2) as eluent, followed by recrystallizationtwice from the mixed solvents of CH2Cl2 and light petroleum toafford TPEB (1.12 g, 43%) as bright orange solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1.24 g | In ethanol; water at 140℃; for 1h; Microwave irradiation; | 1 Example 1 Example 1 [Cu3(btc)2] was prepared in accordance with the following procedure as a PCP for Example 1. 57.6 mL of a 50%-by-volume ethanol aqueous solution was added to 2.11 g of copper (II) nitrate trihydrate and 1.01 g of 1,3,5-benzenetri(methyl carboxylate) to be stirred for 10 minutes and a microwave was applied to this mixture to react this mixture at 140° C. for 60 minutes. A solid was collected by suction filtration and ethanol was added thereto to conduct ultrasonic washing. After the washing, the solid collected by the suction filtration was dried in a vacuum to obtain 1.24 g of the PCP for Example 1. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
4% | Stage #1: 1-(4-dodecyloxy-phenyl)-ethanone With sodium hydride In tetrahydrofuran for 0.333333h; Reflux; Inert atmosphere; Stage #2: 1,3,5-tris-(methoxycarbonyl)benzene In tetrahydrofuran Inert atmosphere; | 3 2.2.6. Synthesis of tri-bdk In a two-necked flask, 4-dodecyloxyacetophenone (1.003 g,3.3 mmol) and NaH (198 mg, 4.95 mmol) were dissolved in THF(20 mL). After stirring for 20 min under N2, the mixture solution was gently heated to refluxing and stirred, until the color of solution turned deep red. A solution of trimethyl benzene-1,3,5-tricarboxylate (252 mg,1 mmol) dissolved in THF (10 mL) was added dropwise, and the reaction was monitored by TLC. After cooling to room temperature, thereaction mixture was quenched carefully with HCl (1 N) until pH < 7. The solid was filtered off, and washed with EA. After recrystallization from THF/acetone, the product was obtained as a pale yellow powder(42 mg, 4%). m.p. 135.5-136.5 °C. 1H NMR (CDC13, 400 MHz): δ 17.11(s, 3H, OH), 8.67 (s, 3H, ArH), 8.03 (d, J=8.2 Hz, 6H, ArH), 7.00 (d,J=8.2 Hz, 6H, ArH), 6.94 (s, 3H, CH), 4.05 (t, J=6.2 Hz, 6H, CH2),1.83 (m, 6H, CH2), 1.47 (m, 6H, CH2), 1.27 (m, 48H, CH2), 0.88 (t,J=6.2 Hz, 9H, CH3). 13C NMR (CDCl3, 100 MHz): δ 186.4, 182.4,163.3, 136.8, 129.6, 128.4, 127.3, 114.54, 92.8, 68.4, 32.0, 29.7, 29.7,29.6, 29.6, 29.4, 29.4, 29.2, 26.0, 22.7, 14.2. HRMS (GCT -TOF, m/z):[M + H]+ C69H97O9, calculated: 1069.7127, found: 1069.7133. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With hydrogenchloride at 35℃; for 1h; Cooling with ice; | 1.2 (2) cyclization reaction Slowly increase the temperature to 35 ° C, and control the temperature at 35 ° C to continue the reaction for 3 h, the intermediate state obtained in step (1) to generate reaction solution A, the reaction solution A was added to 200 L of ice water, adjusted to pH = 6.52 with hydrochloric acid (tune with a pH meter), Continue to stir for 1 h,The white flocculent solid completely precipitated.Filtration and drying give trimethyl 1,3,5-benzenetricarboxylate.See Figure 1 to Figure 6 for the relevant test data. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With hydrogenchloride at 35℃; for 1h; Cooling with ice; | 2.2 (2) cyclization reaction Slowly increase the temperature to 35 ° C, and control the temperature at 35 ° C to continue the reaction for 3 h, the intermediate state obtained in step (1) to generate reaction solution A, the reaction solution A was added to 200 L of ice water, adjusted to pH = 6.52 with hydrochloric acid (tune with a pH meter), Continue to stir for 1 h,The white flocculent solid completely precipitated.Filtration and drying give trimethyl 1,3,5-benzenetricarboxylate. See Figure 1 to Figure 6 for the relevant test data. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1: sodium tetrahydroborate / tetrahydrofuran / 0.5 h / Inert atmosphere; Reflux 2: pyridinium chlorochromate / dichloromethane / 24 h / Reflux 3: trifluoroacetic acid / 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
60% | With oxygen; triethylamine at 20℃; for 30h; Electrochemical reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 63% 2: 19% 3: 8% | With morpholine; ammonium acetate; acetic acid In water monomer at 100℃; for 2h; | Synthesis of 1 and 3 (from Ammonium Acetate and MethylPropiolate in the Presence of Morpholine Acetic Acid Salt) Methyl propiolate (136 mg, 1.62 mmol) and ammonium acetate(248 mg, 3.24 mmol) were dissolved in water (2 mL). To thissolution were added morpholine (48 mg, 0.54 mmol) and aceticacid (32 mg, 0.54 mmol). The reaction mixture was heated at100 °C for 2 h. After cooling, the mixture was extracted withAcOEt (15 mL) and sat. NaHCO3 aq (10 mL). The organiclayer was washed with water (10 mL). The organic layer wasdried over MgSO4 and concentrated in vacuo. Purificationof the crude product by silica gel column chromatography(AcOEt : n-hexane = 1 : 1) gave 92 mg (63%) of 1, 26 mg (19%)of 3, and 8 mg (8%) of 2 |
1: 21% 2: 11% 3: 12% | With ammonium acetate In water monomer at 100℃; for 2h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 46% 2: 25% | With morpholine; acetic acid In water monomer at 100℃; for 2h; | |
1: 21% 2: 32% | In water monomer at 100℃; for 4h; |
Tags: 2672-58-4 synthesis path| 2672-58-4 SDS| 2672-58-4 COA| 2672-58-4 purity| 2672-58-4 application| 2672-58-4 NMR| 2672-58-4 COA| 2672-58-4 structure
[ 713-57-5 ]
4-(Ethoxycarbonyl)benzoic acid
Similarity: 0.95
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