Trimethyl citrate

(i) Preparation of 3-hydroxy-3-methoxycarbonyl-pentanedioic acid dimethyl esterTo a stirred solution of citric acid (9.00 g, 46.8 mmol) in absolute methanol at 0Step 1. General procedure: The mixture of citric acid (11 mmol, 2.11 g), MeOH (20 mL) and N-bromosuccinimide (0.77 mmol, 0.138 g) was stirred in a 25 mL reactor tube at 70 C for 20 h. After the completion of the reaction, the mixture was cooled to room temperature and alcohol was evaporated under reduced pressure.The residue was dissolved in 50 mL of ethyl acetate, washed with the mixture of 10 mL of saturatedNaHCO3 (aq), 10 mL of 10percent Na2S2O3 (aq) and 25 mL of distilled water and the water phase was extractedwith ethyl acetate (2 25 mL). The organic layers were combined, dried with Na2SO4 and the solventwas evaporated under reduced pressure to furnish methyl citrate as a white solid.Yield: 2.55 g, 99percent.FIG. 4 shows examples of COGeneral procedure: 42 mg of citric acid monohydrate was dissolved in 2 mL of solvent; 4 molpercent of Pd/BaS0490 kg (370 1) of anhydrous methylene chloride are added to 1320 kg (753 1) of chlorosulphonic acid (the ratio of methylene chloride to chlorosulphonic acid is 0.5 : 1 by volume). The temperature of the mixture is adjusted to 10-15 oC, and 665.0 kg of citric acid monohydrate are added to it at a rate of 1.25 kg/minute, while the temperature of the reaction mixture is kept between 10 oC and 15 oC. When the addition has been completed the reaction mixture is stirred at a temperature between 10 oC and 15 oC until no more gas is liberated (at least 6 hours). The reaction mixture is then cooled to 3-5 oC and 640 kg (800 1) of anhydrous methanol are added to it at such a rate that the inner temperature does not exceed 25 oC. The reaction mixture is then warmed to 30-35 oC and stirred at the same temperature for 2 hours. The esterifying reaction is completed under this period. The reaction mixture is cooled to 10- 12 oC and 1300 1 of water are added to it at such a rate that the temperature does not exceed 15 oC. To the mixture 800 ml of methylene chloride are added and it is stirred for 15 minutes. The two-phase mixture is clarified for 30 minutes and the organic phase is separated. The aqueous layer is extracted three times with 400 ml each of methylene chloride. The organic phases are combined and washed first with 1000 1 of water, then with a solution of 75 kg of sodium hydrocarbonate in 1000 1 of water. The pH of the solution is adjusted to a value of about 7 by the addition of sodium hydrocarbonate. The organic phase is separated, washed twice with 750 ml each of water and evaporated in vacuo. Evaporation is carried out under a pressure of 3-5 kPa until the inner temperature rises at most to 75 oC. Thus 535 kg of dimethyl 3- OXOGLUTARATE are obtained, which can be used for the further reaction steps without purification. Qualification by gas chromatography: Purity by gas chromatography: Apparatus: gas chromatograph of HP-6850 type Method: Column : HP-1.25 m x 0. 32 MM, 0.17 URN of film thickness Carrier gas: hydrogen Program: 80 oC-5 MINUTES-10 oC/MINUTE-200 oC-8 minutes Detector: FID 280 oC Injector: 200 oC. Expected retention times: Methyl acetoacetate 1.18 minutes Dimethyl 3-oxoglutarate 5.77 minutes Enol ether 8.15 minutes Trimethyl aconitate 10. 00 minutes Trimethyl citrate 10. 42 minutes Isoftalic acid derivative 18.76 minutes Evaluation: by area normalization Result: Methyl acetoacetate: 0.31percent Dimethyl 3-oxoglutarate: 98.33percent Enol ether: 0. 81percent Trimethyl aconitate: 0. 28percent Trimethyl citrate : 0. 09percent Isoftalic acid derivative :- Other contamination (higher than 0, 2 percent) Into a mixture of 100.0 g (58 ml) of chlorosulphonic acid and 30 ml of methylene chloride 50.0 g of citric acid monohydrate are added within 30 minutes at a temperature between 10 oC and 15 oC. The mixture is stirred at the same temperature for 5 hours, cooled to 3-5 oC and 60 ml of methanol are introduced to it within 15 minutes at such a rate that the temperature does not exceed 25 oC. It is then stirred for 2 hours at a temperature between 30 oC and 35 oC, cooled to 15 oC and 100 ml of water are added to it within 15 minutes. The thus-obtained mixture is extracted three times with 50 ml each of methylene chloride; the organic phases are combined, washed successively with 100 ml of saturated sodium hydrogen carbonate solution and 100 ml of water and evaporated in vacuo. Thus 40.8 g of dimethyl 3- OXOGLUTARATE are obtained. Yield: 98. 5 percent Apparatus : gas chromatograph of HP-6850 type Method : Column: HP-1.25 m x 0.32 mm, film thickness of 0. 17 Am Carrier gas: hydrogen Program: 80 oC-5 minutes-10 oC/MINUTE-200 oC-8 minutes Detector: FID 280 oC Injector: 200 oC. Expected retention times: Methyl acetoacetate 1.18 minutes Dimethyl 3-oxo- glutarate 5. 77 minutes Enol ether 8.15 minutes Trimethyl citrate 10.42 minutes Trimethyl aconitate 10.11 minutes Isoftalic acid derivative 18.76 minutes Evaluation: by area normalization Evaluation by gas chromatography (the method was carried out using the parameters specified in Example 1) : Result: Methyl acetoacetate: 0. 49percent Dimethyl 3-OXOGLUTARATE : 97. 62percent Enol ether: 0.98percent Trimethyl citrate: 0. 13percent Trimethyl aconitate: 0.29percent Isoftalic acid derivative: 0.07percent Other contamination (more than 0.2 percent) Example 3 (comparative example) of the Belgian patent specification No. 879, 537 A mixture of 212 ml of chlorosulphonic acid and 600 ml of methylene chloride is prepared (the ratio of methylene chloride to chlorosulphonic acid is 2.83 : 1 by volume). Then 200.0 g of citric acid are added to this mixture within 15-20 minutes, the addition rate of citric acid is 13.3 kg/minute, temperature = 20-22 oC. The reaction mixture is stirred at this temperature for 5 hours, cooled to a temperature between 3'C AND 5 C and 320 ml of methanol are added to it within 15 minutes at such a rate that the temperature remain below 25 oC. The reaction mixture is then stirred for 2 hours at a temperature between 30 oC and 35 oC, cooled to 15 oC, poured into 800 ml of water, stirred vigorously for 15 minutes, clarified for 15 minutes and the phases are separated. The aqueous phase is extracted three times with 150 ml each of methylene chloride. The organic phases are combined, washed once with 400 ml of saturated sodium hydrogen carbonate solution and twice with 200 ml each of water and evaporated in vacuo. Thus 158.2 g of dimethyl 3-oxoglutarate are obtained. Yield: 87. 3 percent. Evaluation by gas chromatography (the method was carried out using the parameters specified in Example 1) : Result: Methyl acetoacetate: 0.21percent Dimethyl 3-oxoglutarate: 91.07percent Enol ether: 4.78percent Trimethyl aconitate 0.46percent Trimethyl citrate : 2.27percent Isoftalic acid derivative: 0.53percent Other contamination (higher than 0. 2percent)

It can be used as the main burning agent for color flame candles, and its melting point and flammability fully meet the requirements of candle products. It is a stable intermediate in the synthesis of medicine and pesticide. It is the main raw material for the production of citrazine acid. It is the main raw material for synthetic hot melt adhesives. It can be used as a blowing agent for methyl methacrylate polymers, a stabilizer for acrylamide, an initiator for polyamide adhesives, and a plasticizer for polyvinyl chloride. Used as organic synthesis intermediates, daily chemical additives safety information

Molecular Weight:234.20
XLogP3:-1
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:7
Rotatable Bond Count:8
Exact Mass:234.07395278
Monoisotopic Mass:234.07395278
Topological Polar Surface Area:99.1
Heavy Atom Count:16
Complexity:266
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes