Sodium (S)-lactate

Chemical Properties

Uses

General Description

Flammability and Explosibility

Biochem/physiol Actions

Synthesis

923031-01-0

923031-02-1

2216-51-5

867-56-1

61597-98-6

The general procedure for the synthesis of L-menthol, sodium L-lactate and (S)-(1R,2S,5R)-2-isopropyl-5-methylcyclohexyl 2-hydroxypropionate from compound (CAS:923031-01-0) and compound (CAS:923031-02-1) is as follows: 1. Preparation of L-lactic acid L-menthyl ester (ML) by esterification reaction: - In a three-necked flask equipped with a Barrett trap, reflux condenser, thermocouple, heating jacket and magnetic stirrer, L-menthol (1440 g), L-(+)-lactic acid (2880 g, an aqueous solution of 88% lactic acid from Purac, HS-88 grade) and heptane (720 g) were added. - The mixture was stirred and refluxed and the resulting water was periodically drained from the trap. - After 32 hours, the reaction was stopped when 854 mL of the aqueous phase was collected and the temperature of the mixture rose to 128 °C. The reaction was stopped by a gas chromatograph. - After cooling to room temperature, the reaction mixture was analyzed by gas-liquid chromatography (GC), which showed the presence of 5.4% unreacted menthol, 67.7% ML, 0.6% propanedioate, 24.6% L-lactoyl-L-lactide (MLL), and 4-butyl L-lactoyl-L-lactoyl-L-lactic acid (MLLL). 2. Controlled hydrolysis: - Dilute the esterified product with water (4230 g) and heptane (960 g). - A 50% aqueous sodium hydroxide solution (809 g) was added dropwise over 30 minutes while stirring and cooling (cold water bath), keeping the temperature not exceeding 30 °C and pH not exceeding 12.9. - After the dropwise addition, stirring was continued for 20 min. the GC analysis showed almost complete conversion of MLL to ML. - The organic layer was separated and washed with 1.5% aqueous lactic acid (1000 g) and azeotroped to remove water. - The solvent (heptane) was evaporated and the residue was fractionated under vacuum to give three fractions: fraction 1 (100 g, 94.5% menthol and 2.0% ML), fraction 2 (111 g, 46.8% menthol and 51.8% ML), and fraction 3 (1860 g, 99.5% pure ML). - The overall yield of ML was 91% based on the initial menthol, and the yield of purified ML was 98% based on the reacted menthol. 3. Sulfuric acid-catalyzed esterification and controlled hydrolysis: - The esterification reaction was carried out using L-menthol (1000 g), L-(+)-lactic acid (1000 g), heptane (500 g) and concentrated sulfuric acid (6 g). - After 2 hours, 300mL of the aqueous phase was collected and the temperature of the mixture was raised to 119°C. - After cooling GC analysis showed the presence of 6.4% unreacted menthol, 57.6% ML, 0.4% propylenol, 32.2% MLL and 1.9% MLLL. - The controlled hydrolysis step was performed with water (800 g) and heptane (500 mL) to dilute the esterification product, and 50% aqueous sodium hydroxide (204 g) was added dropwise over 70 min, keeping the temperature to no more than 30 °C and the pH to no more than 13.1. - The organic layer was separated and further diluted with water (1350 g) and 50% aqueous sodium hydroxide solution (150 g) was added dropwise over 1 hour. - After stirring for 1 h, GC analysis showed almost complete conversion of MLL to ML. - The organic layers were separated, washed and combined, the solvents were evaporated, and vacuum fractionation yielded three fractions: fraction 1 (203 g, 87.1% menthol, 3.5% ML, and 6.2% menthol), fraction 2 (96.8 g, 57.2% menthol and 41.6% ML), and fraction 3 (2356 g, 99.4% pure ML). - The overall yield of ML was 81% based on the initial menthol, and the yield of purified ML was 91% based on the reacted menthol. 4. Controlled hydrolysis (normal addition mode): - In a 500-mL flask, crude ML (88.7 g) was mixed with water (89 g) and heptane (20 g) at a constant temperature to the test temperature. - Under stirring, 50% aqueous sodium hydroxide (35.5 g) was added gradually over 0.6-3.6 h. The pH was recorded periodically. - After the addition was completed, stirring was done until the GC peak of the MLL dropped below 1%. 5. Reverse addition: - A 50% aqueous sodium hydroxide solution (35.5 g) was added to a 500-mL flask and thermostated to the test temperature. - The esterification mixture was gradually added to the aqueous alkali solution with stirring and the pH change was recorded. - This method is not effective at pH 14 or above.

References