| 98% |
With 1,3,5-trichloro-2,4,6-triazine; sodium carbonate at 50℃; for 0.166667h; Sonication; |
General Procedure
General procedure: The carboxylic acid (0.271 mmol), TCT (0.050 g, 0.271 mmol), PS-Ph3P (0.009 g, 0.027 mmol, loading 3.0 mmol/g), and Na2CO3 (0.057 g, 0.542 mmol) were added to MeOH (0.5 mL). Then the mixture was sonicated in an ultrasonic bath (Elmasonic S 30H) at 50°C for the specified time. After completion, the crude mixture was filtered through a short pad of silica to obtain the product after solvent evaporation. Whenever necessary, the product was further purified by flash chromatography. |
| 97% |
With thionyl chloride at 0 - 20℃; |
|
| 97% |
With sulfuric acid In water for 3h; Reflux; |
1.3 (3) Preparation of methyl 4-methylbenzoate (Intermediate 3):
Add 2.72g (20mmol) 4-methylbenzoic acid and 12mL methanol in a 50mL three-necked flask. After stirring to dissolve, slowly drop 1.2mL (22mmol) 98% concentrated sulfuric acid into the system. After the addition is complete, reflux and stir. About 3h. After the reaction was completed, the solvent was removed under reduced pressure, and then dispersed with 50 mL of water, and extracted with ethyl acetate (3×25 mL). The resulting ethyl acetate layer was washed with saturated NaCl aqueous solution and saturated NaHCO3 for 2 times, and then combined with ethyl acetate. The ester layer was dried with anhydrous sodium sulfate and the solvent was removed under reduced pressure to obtain an oily substance with a yield of 97%. |
| 95% |
With sulfuric acid for 18h; Heating; |
|
| 95% |
With potassium carbonate In ethyl acetate for 2h; Heating; |
|
| 95% |
With phosphotungstic acid for 4h; Reflux; |
|
| 95% |
With 1,3-dibromo-5,5-dimethylimidazolidine-2,4-dione at 50℃; for 4h; |
6 Example 6: Preparation of methyl 4-methylbenzoate
Add 10 mmol 4-methylbenzoic acid, 70 mmol methanol, and 1.5 mmol dibromohydantoin into a 50 mL three-necked flask, set up a reflux device, and stir for 4 hours at 50°C.After the methanol was recovered by rotary evaporation, it was transferred to a separatory funnel, and 20 mL of ethyl acetate was added, washed with 5% sodium carbonate solution, washed with water, dried with anhydrous sodium sulfate, and the solvent was removed under reduced pressure to obtain methyl 4-methylbenzoate. 95% rate, |
| 94% |
With sulfuric acid for 5h; Reflux; |
|
| 93% |
With thionyl chloride at 5℃; Heating / reflux; |
B.1; III
To a solution ofp-toluic acid (175g, 1. 28mol) in methanol (2L) was added dropwise thionylchloride (612g, 5. 14mol) under stirring at 5°C. The mixture was refluxed overnight, then the solvent evaporated. The residue obtained was treated with a 10% aqueous NaHC03 solution (pH No. 8). The product was extracted with ethyl acetate, washed with water and dried. The solvent was removed and the crude was purified by column chromatography (pet ether/ethyl acetate) to give methyl-p-toluate as colorless liquid (180g, 93%). |
| 93% |
With sulfuric acid for 24h; Reflux; |
3 4.1.2 General procedure for synthesis of 4-substituted methyl benzoate derivatives 2a-2c
General procedure: 4-substituted benzoic acid 1 (10 mmol) was refluxed in 10 mL MeOH catalyzed by sulfuric acid for 24 h. The solvent was concentrated in vacuo, and the crude product was purified by flash silica gel chromatography (petroleum ether/ethyl acetate = 10:1, v/v) to give the intermediates 2a-2c. |
| 92% |
With aluminum oxide; methanesulfonic acid at 80℃; for 0.0833333h; |
|
| 91.2% |
With sulfuric acid for 0.1h; Microwave irradiation; |
General procedure for synthesis of substituted benzoate:
General procedure: The methyl benzoates, 2a-h were prepared following reportedmethod27 (Table 1).Microwave method: The same procedure as stated abovewas adopted using 100 ml methanol following the other conditionsof microwave irradiated esterification in reactor at 350Watt (power) for 5-8 min. All the esters were recrystallizedusing rectified spirit except 2a, a fluoro compound which wasa liquid (Table 1). |
| 90% |
With sulfuric acid for 10h; Reflux; Sealed tube; |
|
| 90% |
With oxygen; potassium carbonate In hexane at 20℃; for 14h; Sonication; |
|
| 90% |
With 1,3-dibromo-5,5-dimethylimidazolidine-2,4-dione at 70℃; for 20h; |
3.2.1. General Procedure for the Esterification between Carboxylic Acids and Alcohols
General procedure: The mixture of carboxylic acid, alcohol, and 1,3-dibromo-5,5-dimethylhydantoin was stirredin a 25 mL reactor tube at 70 °C for 2-40 h. After reaction completion, the mixture was cooled toroom temperature and the alcohol was evaporated under reduced pressure. The isolation procedurewas as follows, except where noted dierently in the Supporting Information. The residue wasdissolved in 10 mL ethyl acetate and washed with a mixture of 1 mL saturated NaHCO3(aq), 1 mLsaturated Na2S2O3(aq), and 10 mL distilled water, and the water phase was extracted with ethyl acetate(2 10 mL). The organic layers were combined, dried over Na2SO4, and the solvent was evaporatedunder reduced pressure |
| 88% |
With Oxone In toluene at 60℃; for 48h; Green chemistry; |
|
| 86.6% |
With sulfuric acid Reflux; |
3.1 General procedure for the synthesis of compounds
General procedure: A mixture of organic acid (0.5 g) and methanol (100 ml) was heated under reflux in presence of sulphuric acid (0.8 ml) until the completion of the reaction which was checked by single spot TLC. Then, methanol was removed under reduced pressure a half and the solution was diluted with 20 ml of water. The product was extracted with ethyl acetate (30 ml). The organic phase was neutralized successively with NaHCO3 5%and water, dried over anhydrous Na2SO4, and filtered. The ethyl acetate phase was separated, which on evaporation yielded the ester derivatives |
| 85% |
With bromobenzene at 55 - 60℃; for 4h; Autoclave; |
General procedure for the esterification
General procedure: benzoic acid (Table 3, entry 1) (1.0 g,0.0081 mol), bromobenzene (0.125 g, 0.0081 mol), 10% palladium on carbon(50% wet) (0.2 g) and methanol (3 mL) were placed in autoclave vessel. Autoclave was pressurized with 1-2 bar of nitrogen followed by 1-2 bar of hydrogen gas and then put under the desired pressure of hydrogen (5-6 bar).The reaction mixtures are then warmed to 55-60 C temperature and stirredfor 4 h at 300 rpm. After reaction, the catalyst was filtered through celite bed.Filtrate was added with water (30 mL). The reaction mixture was extracted with isopropyl acetate (2 15 mL). The combined organic layers were washedwith 5% aqueous sodium bicarbonate solution (2 15 mL), dried over anhydrous Na2SO4 and filtered. The filtrate was evaporated under vacuum togive of methyl benzoate product |
| 84% |
With N-Bromosuccinimide at 70℃; for 20h; |
3.2.1. General Procedure for the Esterification between Carboxylic Acids and Alcohols
General procedure: The mixture of carboxylic acid, alcohol and N-bromosuccinimide was stirred in a 25 mL reactortube at 70 °C for 2-40 h. After the completion of the reaction, the mixture was cooled to roomtemperature and alcohol was evaporated under reduced pressure. The isolation procedure was as follows, except where noted differently in Section 3.2.6. The residue was dissolved in ethyl acetate andconsecutively washed with 10 mL of 10% Na2S2O3 (aq), 5 mL of saturated NaHCO3 (aq) and 10 mL ofdistilled water. The water phase was extracted with ethyl acetate (3Χ5 mL). The organic layers were combined, dried over Na2SO4 and the solvent was evaporated under reduced pressure. |
| 83% |
With sulfuric acid |
|
| 82% |
With sulfuric acid for 6h; Reflux; |
General procedure for the preparation of methyl esters(17a-j)
General procedure: A catalytic amount of concentrated H2SO4 wasadded to a solution of carboxylic acids 16(a-j) (1.0 mmol)in 50 mL of methanol, and the mixture was refluxed for 6 h. It was allowed to cool. The saturated solution ofNaHCO3 was added to the reaction mixture, and it wasextracted with EtOAc (2 X 50 mL). The combined organiclayer was dried Na2SO4 and concentrated to obtain puremethyl esters 17(a-j). |
| 74% |
With trifluoromethylsulfonic anhydride; triethylamine; Triphenylphosphine oxide In 1,2-dichloro-ethane at 25℃; for 0.25h; other carboxylic acids, other alcohols; |
|
| 74% |
With trifluoromethylsulfonic anhydride; triethylamine; Triphenylphosphine oxide In 1,2-dichloro-ethane at 25℃; for 0.25h; |
|
| 73% |
With sulfuric acid for 12h; Reflux; |
2 Procedure:
In a 20 mL round bottomed flask, 4-methylbenzoic acid (1.36 g, 0.01 mol), methanol (10 mL), and a catalytic amount of concentrated H2SO4 (~1 drop) were combined and stirred at reflux for 12 hours. Methanol was then removed under reduced pressure. The crude material was taken up in ethyl acetate and washed three times with deionized water. The organic layer was dried over sodium sulfate, the solvent was removed under reduced pressure, and the resulting crude material was purified via silica column chromatography eluting with a gradient from 0 to 10% ethyl acetate/hexanes solution. The product was the first compound to come off of the column. Removal of the solvent afforded a thin clear residue. Yield: 1.10 g (73%). 1H-NMR (300 MHz, CDCl3) δ ppm 7.87 (d, 2H), 7.17 (d, 2H), 3.83 (s, 3H), 2.34 (s, 3H). |
| 73% |
With sulfuric acid for 12h; Reflux; |
2.A A. Synthesis of methyl-4-methylbenzoate--small molecule analogue of PET
j00120j To identify the appropriate conditions for aminolysis of polyesters with primary amines, reactions were first studied using a small molecule analogue of PET. The products of the reaction between the small molecule analogue and a primary amine can be isolated and characterized using traditional analytical methods (NMR, IR, MS). Methyl-4- methylbenzoate was chosen as a suitable analogue for PET due to its similarity in structure to the ester in the PET repeat unit. Methyl-4-methylbenzoate was synthesized using FischerSpeier esterification in methanol with catalytic sulfuric acid.j00121j Procedure: In a 20 mL round bottomed flask, 4-methylbenzoic acid (1.36 g, 0.01 mol), methanol (10 mL), and a catalytic amount of concentrated H2504 (1 drop) were combined and stirred at reflux for 12 hours. Methanol was then removed under reduced pressure. The cmde material was taken up in ethyl acetate and washed three times with deionized water. The organic layer was dried over sodium sulfate, the solvent was removed under reduced pressure, and the resulting crude material was purified via silica column chromatography eluting with a gradient from 0 to 10% ethyl acetate/hexanes solution. The product was the first compound to come off of the column. Removal of the solvent afforded a thin clear residue. Yield: 1.10 g (73%). ‘H-NMR (300 MI-Tz, CDC13) ö ppm 7.87 (d, 2H), 7.17 (d, 2H), 3.83 (s, 3H), 2.34 (s, 3H). |
| 72% |
With <Ph3P(+)>2O*2SO3F(-); triethylamine In 1,2-dichloro-ethane for 0.25h; |
|
| 70.6% |
With sulfuric acid at 65℃; for 7h; |
2.1 (1) Preparation of methyl p-toluate
In a dry 100ml three-necked flask, add 8g of p-toluic acid and 50ml of dried methanol, add 0.4ml of concentrated sulfuric acid dropwise slowly while stirring, and react for 7h under reflux conditions at 65°C. During the reaction, TLC monitors the reaction (developing solvent: ethyl acetate: petroleum ether = 1:3), until the reaction progresses more than 90%, the reaction is terminated. Use a rotary evaporator to remove at least 80% methanol from the system, add 40ml of water to the remaining liquid, extract with ethyl acetate (3×20ml), and wash the organic phase with 10ml 10% NaHCO3 solution 2-3 times (TLC monitoring room The methylbenzoic acid point disappeared completely), and then the organic phase was washed once with 10 ml of water, and the obtained organic phase was dried with anhydrous MgSO4 overnight. Suction filtration and rotary evaporation yielded 6.5 g of product, which was colorless to pale yellow liquid, and the yield was 70.6%. |
| 69% |
With 1-(4-Nitrophenyl)-1H-imidazole-3-ium trifluoromethanesulfonate at 80℃; for 12h; Sealed tube; Green chemistry; |
2.2. General procedure for the synthesis of biodiesel
General procedure: A magnetic stir bar placed in a sealed tube, Free Fatty Acids (FFAs), methanol, and ionic liquids were added. The esterification was then carried out for a length of time at a specific temperature with vigorous stirring. After the reaction was completed, the residue was cooled to room temperature and kept at the same temperature until phase separation. The reaction mixture was extracted with ether and water. The upper phase (volume) mainly containing the desired ester could be isolated simply by liquid/liquid phase separation, concentrated, and column chromatography; the bottom phase ionic liquid in water from the reaction could be reused after removal of water under reduced pressure. For several experiments separated organic phase was directly concentrated and the product was confirmed by NMR spectrometry/ mass spectrometry. |
|
With hydrogenchloride In water at 25℃; |
|
|
With sulfuric acid |
|
|
With hydrogenchloride |
|
| 96.5 % Spectr. |
With iron(III) sulfate; sulfuric acid for 2h; Heating; |
|
|
With thionyl chloride |
|
|
With sulfuric acid Heating; |
|
|
With sulfuric acid for 4h; Reflux; |
|
|
With sulfuric acid at 20℃; for 48h; |
|
|
Acidic conditions; Reflux; |
|
|
With sulfuric acid Reflux; |
|
|
With sulfuric acid Inert atmosphere; Reflux; |
|
|
With sulfuric acid at 100℃; for 24h; |
|
|
Reflux; Acidic conditions; |
|
|
With sulfuric acid for 4h; Reflux; |
4.1.1. General procedure for the synthesis of methyl esters (2a-o)
General procedure: Each substituted benzoic acid (1) (0.04 mol) was heated at reflux for 4 hours in 50.0 mL (1.23 mol) of anhydrous methanol and 1.0 mL (2.0 mmol) of sulfuric acid. The solvent was concentrated and the product obtained washed with cold water. In some cases, as for non-substituted compounds, the ester showed an oily aspect and, to promote its precipitation, the compound was cooled by immersion in dry ice-ethanol bath. |
|
With sulfuric acid |
2.2.2. Synthesis of p-substituted benzoic hydrazides
General procedure: Methyl benzoates were synthesized from their respective p-substituted benzoic acids, using excess dry methanol in the presence of H2SO4. para-Substituted benzoic hydrazides (2a-i) were prepared by reaction of the corresponding methyl benzoates (10 mmol) with hydrazine hydrate 99% (50 mmol) in methanol under reflux for 4-6 h. The excess solvent was removed under vacuum and the residue was filtered under suction, washed with water, and dried. The spectral and analytical data of benzoic hydrazide (2a) [26], 4-bromobenzoic hydrazide (2b) [27], 4-chlorobenzoic hydrazide (2c) [28], 4-fluorobenzoic hydrazide (2d) [26], 4-hydroxybenzoic hydrazide (2e) [29], 4-methoxybenzoic hydrazide (2f) [30], 4-methylbenzoic hydrazide (2g) [28], 4-nitrobenzoic hydrazide (2h) [28] and 4-aminobenzoic hydrazide (2i)[28] are in good agreement with literature values. |
|
With sulfuric acid |
2.2.2. Synthesis of p-substituted benzoic hydrazides 2a-i
General procedure: Methyl benzoates were synthesized from their respective p-substituted benzoic acids, using excess of dry methanol in presence of H2SO4. p-Substituted benzoic acid hydrazides (2a-i) were prepared by reaction of the corresponding methyl benzoates (10 mmol) with hydrazine hydrate 99% (50 mmol) in methanol under reflux for 4-6 h. The excess solvent was removed under vacuum and the residue was filtered under suction, washed with water and dried. The spectral and analytical data of benzoic hydrazide (2a) [35], 4-bromobenzoic hydrazide (2b) [36], 4-chlorobenzoic hydrazide (2c) [37], 4-fluorobenzoic hydrazide (2d) [35], 4-hydroxybenzoic hydrazide (2e) [38], 4-methoxybenzoic hydrazide (2f) [39], 4-methylbenzoic hydrazide (2g) [37], 4-nitrobenzoic hydrazide (2h) [37] and 4-aminobenzoic hydrazide (2i) [38] are in good agreement with literature values. |
|
With sulfuric acid |
|
|
With sulfuric acid for 6h; Reflux; |
|
|
With sulfuric acid Reflux; |
|
|
With sulfuric acid at 80℃; for 4h; |
|
|
Acidic conditions; Reflux; |
|
|
With sulfuric acid |
|
|
With sulfuric acid for 3h; Inert atmosphere; Schlenk technique; Reflux; |
|
|
With sulfuric acid for 4h; Reflux; |
4.1.1. General procedure for the synthesis of benzhydrazides (2a-j)
General procedure: Each substituted benzoic acid (1) (0.02 mol) was refluxed for 4 h in 20.0 mL (0.49 mol) of anhydrous methanol and 0.5 mL (0.01 mol) of sulphuric acid. The reaction mixture was cooled down to room temperature and the hydrazine hydrate 80% (v/v) (10.0 mL, 0.13 mol) was added. The system was maintained by vigorously stirring for more 30 min in reflux. In the case of compound with 4-nitro substituent group attached to the benzene moiety, after the addition of hydrazine hydrate 80% (v/v) at room temperature, the reaction mixture was cooled down in ice bath and maintained into stirring during 1 h. After this period, the mixture was maintained at low temperature to give 2.19,22 |
|
With sulfuric acid at 20℃; |
|
|
With thionyl chloride for 2h; Reflux; |
|
|
With sulfuric acid for 4h; Reflux; |
|
|
With sulfuric acid for 6h; Reflux; |
|
|
With sulfuric acid Reflux; |
5 4.2. General procedure for the synthesis of Isatin based Schiff basesderivatives (1-20)
General procedure: Isatin based Schiff bases (1-20) were synthesized in three steps,first an esterification carried out by reacting different carboxylicacid with methanol in sulphuric acid (2-3 ml) under reflux conditionfor 12-16 h. The completion of reaction was monitored byTLC. After completion of reaction, reaction mixture was extractedwith hexane to obtained pure esters. Then esters were refluxedwith hydrazine hydrate in methanol with few drops of glacial aceticacid for 3 h. After completion of reaction, reaction mixture waswashed with chloroform to obtained different hydrazides. Thesehydrazides (1mmole) each were than treated with different Isatin(1mmole) in methanol having catalytic amount of glacial acetic acidfor 2-4 h. Reaction completion was monitored through periodicTLC. After completion of reaction, reaction mixture was washedwith n-hexane to obtain our desired products (1-20). The structureof all compounds was established through EI-MS and 1H NMR. |
|
With thionyl chloride |
|
|
With sulfuric acid |
|
|
Acidic conditions; |
|
|
With sulfuric acid Reflux; |
|
|
With sulfuric acid Reflux; |
|
|
With glycerol-based sulfonic acid functionalized carbon catalyst for 6h; Reflux; Green chemistry; |
General Procedure for the Synthesis of Methyl Esters (2a-t)
General procedure: To a stirred solution of substituted aryl carboxylic acid 1 (0.15 mol) in methanol (0.75 mol) glycerol-based solid acid catalyst (28 wt% of aryl carboxylic acid) was added and heated to reflux for 6 h. After completion of the reaction as indicated by TLC, the reaction mixture was cooled to room temperature. The catalyst was separated by filtration and was washed with methanol for recycle. Methanol was then distilled off under reduced pressure to get the pure methyl ester 2. |
|
With sulfuric acid for 5h; Reflux; |
|
|
With sulfuric acid for 4h; Reflux; |
General procedure for the synthesis ofbenzohydrazides (3a-e)
General procedure: The substituted benzoic acid (2.46 m mol)was reuxed with methanol in sulphuric acid for 4h.The ester formed reacts with hydrazine and getsconverted to benzohydrazides by hydrozinolysis22. |
|
With sulfuric acid at 65 - 67℃; for 4h; |
|
|
With thionyl chloride |
1.1
First, p-methylbenzoic acid is mixed in an equimolar amount with methanol.The reaction was dehydrated to give methyl p-toluate (I). The product (1) was mixed with excess hydrazine hydrate and reacted in an oil bath at 80 °C. for 2 h to give p-methylbenzoyl hydrazide (II). |
|
With sulfuric acid for 12h; Reflux; |
5.3. Representative Procedure for the Synthesis of Hydrazones(8a-e and 12a-e).
General procedure: A mixture of 2-fluorobenzoic acid (5a)(1 g, 7.13mmol) in MeOH (20 mL) was stirred for a fewminutes. Concentrated H2SO4 (1 mL) was added, and themixture was refluxed for 12 h. The reaction was monitoredby TLC using -hexane, with ethyl acetate as a developingsystem.CH2Cl2 (30 mL) was then added, and the mixture wasextracted with distilled H2O (3 × 20 mL).The organic phasewas separated, dried on anhydrous Na2SO4, and evaporatedunder vacuum to afford corresponding ester 6a in almostquantitative yield in oil form (1.09 g). |
|
With thionyl chloride |
1 The first step: see Figure 1, the synthesis of anisic aldehyde - [5-(p-methylphenyl) -1,3,4thiadiazole-2-mercapto]-acetyl hydrazine
First, p-toluic acid and methanol are mixed in an equimolar ratio to dehydrate the reaction.This gave methyl p-toluate (I). |
|
With sulfuric acid Reflux; |
|
|
With thionyl chloride |
1.1 first step:
First, p-toluic acid and methanol are mixed in an equimolar manner, and the reaction is dehydrated to obtain methyl p-toluate (I).The product (I) was mixed with excess hydrazine hydrate and reacted in an oil bath at 80° C. for 2 h to give p-methylbenzoyl hydrazide (II). |
|
With sulfuric acid Reflux; |
General procedure for synthesis of hydrazides (5a-l)1
General procedure: Carboxylic acids (10 mmol) were refluxed for 1-2 h in methanol (5 mL) in presence of conc. H2SO4 (catalytic amount) with continuous stirring. The reaction was monitored by TLC till the acids were fully converted to the corresponding esters [Eluent: EtOAc/Hexanes (1:4)]. The reaction mixture was allowed to cool down to room temperature and hydrazine monohydrate 80% (40 mmol, 1.91 mL) was added slowly in an ice bath. The reaction was then warmed to room temperature and refluxed for another 1-2 h and followed by TLC till formation of hydrazide. The reaction mixture was kept at refrigerator till the product precipitated. All hydrazides were isolated in quantitative yields and in a pure form. There melting points were in full agreement with the literature melting points of the same compounds. |
|
With sulfuric acid at 85℃; |
|
|
With thionyl chloride at 45℃; for 5h; |
5.3.1. typical procedure for the synthesis of 1,3,4-oxadiazol-2(3H)-oneintermediates (18)
General procedure: The substituted benzoic acid 15 (6 mmol) was dissolved in 20 mL MeOH, SOCl2 (1.4 g, 12 mmol) was added slowly in ice-bath, then themixture was heated at 45 °C for 5 h. Upon completion, the mixture was concentrated, the residue was re-dissolved in EtOAc and washed with NaHCO3 and brine. The organic layer was dried with Na2SO4 and concentrated to give the desired ester intermediate 16, which was used in the next step without further purification.The above ester 16 was dissolved in 15 mL MeOH, hydrazine hydrate(2 mL, 32 mmol), then the mixture was heated at 45 °C for 5 h.Upon completion, the mixture was concentrated, the residue was redissolved in EtOAc and washed with brine. The organic layer was concentrated and purified by silica gel affording the desired acylhydrazine intermediate 17 as a white solid in good yield.Add benzhydrazide 17 (2 mmol), CH2Cl2 (20 mL) and DIPEA(0.52 g, 4 mmol) to a round bottomed flask under N2 protection.Triphosgene (0.3 g, 1 mmol) dissolved in DCM (4 mL) Using a syringe,the triphosgene/DCM solution was added dropwise to the stirred solutionof hydrazide, and stirred at room temperature for 1 h. The reactionmixture was concentrated by rotary evaporation, the crudeproduct was purified by chromatography on silica (DCM/MeOH=100:1) affording the desired products 18 as white solid (about70% yield for three steps). Example 18-D3, 1H NMR (600 MHz,DMSO-d6) δ 12.66 (s, 1H), 7.80 (d, J=8.6 Hz, 2H), 7.62 (d, J=8.6 Hz,2H). ESI-MS calcd for C8H4ClN2O2 [M-H]-, 195.0, found 195.2. |
|
With sulfuric acid Reflux; |
Synthesis of esters (2) from aromatic carboxylic acids (1)
General procedure: The mixture of corresponding carboxylic acid (2 mmol),methanol (15 ml) in the presence of concentration sulfuricacid (2 mmol) were refluxed until monitoring by TLCindicated the end of the reaction. The excess of alcohol wasdistilled off under reduced pressure. The reaction mixture issolidified by cooling to room temperature. After filtering offthe crystal and washing with distilled water to remove thesulfuric acid, the residue was recrystallized from ethanoland distilled water. |
|
With sulfuric acid Reflux; |
|
|
With sulfuric acid for 2h; Reflux; |
4.1.1. General procedure for the preparation of hydrazides 8
General procedure: Carboxylic acids 1a-g (5 mmol) were heated under reflux in methanol(5 mL) for 2 h in presence of conc. H2SO4 (catalytic amount)with continuous stirring. The reaction was monitored by TLC till theacids were fully converted to the corresponding esters [Eluent: EtOAc/Hexanes (1:4)]. The reaction mixture was allowed to cool down to roomtemperature and hydrazine monohydrate 80% (20 mmol, 0.96 mL) wasadded slowly in an ice bath. The reaction was then warmed to roomtemperature and heated under reflux for another 1-2 h and followed byTLC till formation of hydrazide. The reaction mixture was kept at refrigeratortill the product precipitated. All hydrazides were isolated inquantitative yields and in a pure form. Their melting points were in fullagreement with the literature melting points of the same compounds. |
|
With sulfuric acid for 8h; Reflux; |
4.2 General procedure for the synthesis of compounds 2a-2q
General procedure: The substituted benzoic acid 11q (1 eq.) in methanol was refluxed for 8h. The reactions were completed monitored by TLC (PE/EA=3:1). Then cooling to rt, the solution was adjusted to pH=7 with NaOH. The mixture was extracted with ethyl acetate and washed with brine to give the crude product. |
|
With sulfuric acid at 80℃; for 8h; |
In one embodiment, the esterification reaction includes: adding 136 grams (1 mol) of p-toluic acid and 400 mL of methanol to the reaction flask, adding 5.2 grams (0.05 mol) of concentrated sulfuric acid dropwise, and heating at 80°C. The reaction was refluxed for 8 hours, then methanol was distilled off under reduced pressure, 400mL of water was added to the reaction flask, 1,2-dichloroethane (200mL×3 times) was extracted to remove impurities, and the organic layer was washed once with saturated brine (200mL) The organic layer was separated to obtain methyl 4-methylbenzoate, which was then directly put into the next bromination reaction. |
|
With thionyl chloride at 20℃; for 3h; Reflux; |
|
|
With sulfuric acid for 12h; Reflux; |
|
|
With sulfuric acid for 3h; Reflux; |
Substituted methyl benzoates 2a-2d (generalprocedure).
General procedure: Substituted benzoic acid 1a-1d (0.01 mol)was dissolved in 20 mL of anhydrous methanol,3.0 mL of concentrated sulfuric acid was added, andthe mixture was refluxed for 3 h. After completion ofthe reaction (TLC, ethyl acetate-hexane, 30:70), themixture was poured into a 500-mL separatory funnel, 100 mL of distilled water and 10% aqueous NaHCO3were added to remove unreacted carboxylic acid. Themixture was extracted with 100 mL of diethyl ether,and the extract was evaporated. |
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