| 51.71% |
With sodium hydroxide; water In n-heptane at 15 - 60℃; for 0.6 - 3.6 h; |
Preparation of l-Menthyl Lactate by Esterification and Controlled HydrolysisEsterification: A three-neck flask equipped with a Barrett trap, reflux condenser, thermocouple, heating mantle, and magnetic stirrer is charged with l-menthol (1440 g), L-(+)-lactic acid (2880 g of grade HS-88 from Purac, 88percent lactic acid in water), and heptane (720 g). The stirred mixture is brought to reflux and water is periodically drained from the trap as it forms. The temperature of the mixture increases gradually to 128° C. after 32 h and after 854 mL of aqueous phase has been removed. The mixture is cooled to ambient temperature and analyzed by gas-liquid chromatography (GC). It contains: 5.4percent of unreacted menthol, 67.7percent of l-menthyl L-lactate (ML), 0.6percent of lactide (cyclic dimer of lactic acid), 24.6percent of l-menthyl L-lactoyl-L-lactate (MLL), and 0.4percent of l-menthyl L-lactoyl-L-lactoyl-L-lactate (MLLL).Controlled hydrolysis: The esterified product is diluted with water (4230 g) and heptane (960 g). Aqueous sodium hydroxide (809 g of 50percent NaOH) is then added dropwise over 30 min. while the mixture is stirred and cooled (cold water bath) so that the temperature does not exceed 30° C. and the pH does not exceed 12.9. After the base addition, the mixture stirs for another 20 min. GC analysis shows practically complete conversion of MLL into ML. The layers are separated. The organic layer is washed with 1.5percent aqueous lactic acid (1000 g) and then cohobated to remove moisture. The solvent (heptane) is stripped, and the residue is fractionally distilled under vacuum with the following results:Fraction 1, 100 g, 94.5percent menthol and 2.0percent of ML.Fraction 2, 111 g, 46.8percent menthol, 51.8percent ML.Fraction 3, 1860 g, 99.5percent pure ML.Yield of ML contained in all three fractions based on charged menthol: 91percent. Yield of purified ML based on reacted menthol: 98percent; Preparation of l-Menthyl Lactate by Sulfuric Acid-Catalyzed Esterification and Controlled HydrolysisEsterification: The procedure of Example 1 is generally followed using 1000 g of l-menthol, 1000 g of L-(+)-lactic acid, 500 g of heptane, and 6 g of concentrated sulfuric acid. The temperature of the mixture increases gradually to 119° C. after 2 h and after 300 mL of aqueous phase has been removed. The mixture is cooled and analyzed by GC. It contains: 6.4percent of unreacted menthol, 57.6percent of ML, 0.4percent of lactide, 32.2percent of MLL, and 1.9percent of MLLL.Controlled hydrolysis: The esterified product is diluted with water (800 g) and heptane (500 mL). Aqueous sodium hydroxide (204 g of 50percent NaOH) is then added dropwise over 70 min. while the mixture is stirred and cooled (cold water bath) so that the temperature does not exceed 30° C. and the pH does not exceed 13.1. The layers are separated. The organic layer is diluted with water (1350 g) and treated with more 50percent aq. sodium hydroxide (150 g), which is added dropwise over 1 h in the manner described above. After the base addition, the mixture stirs for about 1 h. GC analysis shows practically complete conversion of MLL into ML. The layers are separated. The organic layer is washed with water.The entire procedure of esterification and controlled hydrolysis is repeated. The washed organic layers are combined, the solvent (heptane) is stripped, and the residue is fractionally distilled under vacuum with the following results:Fraction 1, 203 g, 87.1percent menthol, 3.5percent ML, and 6.2percent menthenes.Fraction 2, 96.8 g, 57.2percent menthol, 41.6percent ML.Fraction 3, 2356 g, 99.4percent pure ML.Yield of ML contained in all three fractions based on charged menthol: 81percent. Yield of purified ML based on reacted menthol: 91percent; Controlled Hydrolysis: Normal Mode of AdditionThese examples illustrate that desirable results are obtained by addition of the aqueous base to the esterification mixture at various temperatures at pH below 14.General procedure. In a 500-mL flask equipped with a magnetic stirrer, thermocouple, and pH probe, crude ML (88.7 g, obtained as described above in Example 3) is mixed with water (89 g) and heptane (20 g). The mixture is brought to the test temperature using a thermostat. While stirring, 50percent aq. NaOH (35.5 g) is then pumped gradually (0.6-3.6 hours) into the thermostatted flask, and pH is recorded periodically. After base addition, the mixture is agitated for several minutes until the GC peak corresponding to MLL drops below 1percent. Results appear in Table 1; Reverse AdditionThese examples illustrate that less desirable results are obtained when the esterification mixture is added to the aqueous base (i.e., reverse addition), with pH reaching or exceeding 14.General Procedure. Aqueous NaOH (35.5 g of 50percent solution) is charged to a 500-mL flask equipped with a magnetic stirrer, thermocouple, and pH probe. The stirred mixture is brought to the test temperature using a thermostat. In a separate flask, crude ML (88.7 g, obtained as described in Example 3) is mixed with water (89 g) and heptane (20 g). The stirred mixture is pumped over 0.6-3.6 hours into the thermostatted flask containing aqueous base. Results appear in Table 2; This example illustrates that too much aqueous base gives a less desirable result even with normal addition.The procedure of Example 7 is followed, except that 50 g of aqueous 50percent NaOH is used instead of 35.5 g. The composition of the reaction mixture (GC) is as follows: 44.81percent of l-menthol, 55.05percent ML, and 0.14percent of MLL. |
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