Lactic esterification

Many of the physical properties are not affected by the optical composition, with the important exception of the melting poiat of the crystalline acid, which is estimated to be 52.7—52.8°C for either optically pure isomer, whereas the reported melting poiat of the racemic mixture ranges from 17 to 33°C (6). The boiling poiat of anhydrous lactic acid has been reported by several authors it was primarily obtained duriag fractionation of lactic acid from its self-esterification product, the dimer lactoyUactic acid [26811-96-1]. The difference between the boiling poiats of racemic and optically active isomers of lactic acid is probably very small (6). The uv spectra of lactic acid and dilactide [95-96-5] which is the cycHc anhydride from two lactic acid molecules, as expected show no chromophores at wavelengths above 250 nm, and lactic acid and dilactide have extinction coefficients of 28 and 111 at 215 nm and 225 nm, respectively (9,10). The iafrared spectra of lactic acid and its derivatives have been extensively studied and a summary is available (6). 

Reactions and Uses. The common reactions that a-hydroxy acids undergo such as self- or bimolecular esterification to oligomers or cycHc esters, hydrogenation, oxidation, etc, have been discussed in connection with lactic and hydroxyacetic acid. A reaction that is of value for the synthesis of higher aldehydes is decarbonylation under boiling sulfuric acid with loss of water. Since one carbon atom is lost in the process, the series of reactions may be used for stepwise degradation of a carbon chain. 

As a model esterification reaction, the formation of ethyl lactate has been studied and its complete kinetic and thermodynamic analysis has been performed. The formation rate of ethyl lactate has been examined as a function of temperature and catalyst loading. In early experiments, it was determined that lactic acid itself catalyzes esterification, so that there is significant conversion even without ion exchange resin present. The Arrhenius plot for both resin-catalyzed and uncatalyzed reactions indicates that the uncatalyzed... 

The equilibrium conversion of lactic acid was measured by allowing reaction to proceed until no further changes were observed. We then used the data to calculate the equilibrium constant for the esterification reaction as a function of temperature. The final form of the equilibrium constant is given by the following equation. 

Jso-propyl lactate has been prepared by heating iso-propyl alcohol and lactic acid in a sealed tube at 1700,1 2 and from silver lactate and iso-propyl iodide, together with the iso-propyl ester of a-iso-propoxy-propionic acid.3 Direct esterification of the acid with the alcohol, with sulfuric acid, has failed to give a yield greater than 20 per cent of the theoretical amount, and the product has been less pure. 

Two methods of prepn are listed in Ref 3 a)By esterification of lactic acid with ethanol and b)By combining acetaldehyde with hydrocyanic. acid to form acetaldehyde cyanohydrin, and this is treated wi th ethanol HC1 to ethyl lactate. Used as a solvent for cellulose acetate and nitrate, other cellulose esters, resins, lacquers, paints and enamels Refs l)Beil 3, 264, 267, 280,(102,109) ... 

Problem 5.9 Esterification of ( + )-lactic acid with methyl alcohol gives (-)-methyl lactate. Has the configuration changed ... 

Fruity flavor in dairy products is the result of ethyl ester formation, usually catalyzed by esterases from psychrotrophic or lactic acid bacteria. Ester formation by P. fragi involves liberation of butyric and ca-proic acids from the one and three positions of milk triglycerides and the subsequent enzymatic esterification of these fatty acids with ethanol (Hosono et al. 1974 Hosono and Elliott 1974). Consequently, among the esters formed, ethyl butyrate and ethyl hexanoate predominate. Pseudomonas-produced fruity flavor can occur in fluid milk, cottage cheese, and butter. 

Fruity flavor in Cheddar cheese is also associated with high levels of ethyl butyrate and ethyl hexanoate (Bills et al. 1965). However, this defect is usually caused by esterase activity from lactic acid bacteria, especially S. lactis and S. lactis subsp. diacetylactis (Vedamuthu et al. 1966). Fruity-flavored cheeses tend to have abnormally high levels of ethanol, which is available for esterification (Bills et al. 1965). Streptococcal esterase activity in cheese is affected by the level of glutathione, which suggests a dependence on free sulfhydral groups for activity (Harper et al. 1980). 

In addition to the more or less popular methods of depsipeptide synthesis discussed vide supra, there are also a limited number of complementary and effective synthetic procedures that have been described for this purpose. Among these, the well-known method of symmetric anhydrides from N-protected amino acids has to be considered. This method has found successful use in the esterification of hydroxy acids in the presence of some catalyst additives. Initially, the addition of pyridine11091 or 1-hydroxybenzotriazole in pyridine1 101 to a symmetric anhydride was utilized for ester bond formation. As an example, Katakai has prepared a number of didepsipeptides in 85-96% yield by means of a 2-nitrophenylsulfenyl /V-carboxy anhydride with lactic acid derivatives in the presence of pyridine.1 09 ... 

If we convert (+)-lactic acid into its methyl ester, we can be reasonably certain that the ester will be related in configuration to the acid, because esterification should not affect the configuration about the chiral carbon atom. It happens that the methyl ester so obtained is levorotatory, so we know that (+)-lactic acid and (—)-methyl lactate have the same relative configuration at the asymmetric carbon, even if they possess opposite signs of optical rotation. However, we still do not know the absolute configuration that is, we are unable to tell which of the two possible configurations of lactic acid, 2a or 2b,... 

Medium Boiling Esters. Esterification of ethyl and propyl alcohols, ethylene glycol, and glycerol with various acids, eg, chloro- or bromoacetic, or pyruvic, by the use of a third component such as benzene, toluene, hexane, cyclohexane, or carbon tetrachloride to remove the water produced is quite common. Benzene has been used as a co-solvent in the preparation of methyl pyruvate from pyruvic acid (101). The preparation of ethyl lactate is described as an example of the general procedure (102). A mixture of 1 mol 80% lactic acid and 2.3 mol 95% ethyl alcohol is added to a volume of benzene equal to half that of the alcohol (ca 43 mL), and the resulting mixture is refluxed for several hours. When distilled, the overhead condensate separates into layers. The lower layer is extracted to recover the benzene and alcohol, and the water is discarded. The upper layer is returned to the column for reflux. After all the water is removed from the reaction mixture, the excess of alcohol and benzene is removed by distillation, and the ester is fractionated to isolate the pure ester. 

Esterification—Continued by azeotropic distillation with benzene, 22, 38 by nitric acid, 22, 65 of desoxycholic acid, 24, 41 of lactic acid, 26, 4 of linoleic acid, 22, 77 of linolenic acid, 22, 83 of pyruvic acid with use of methyl ester column, 24, 72 Ester interchange, 26, 5, 19 between polylactic acid and allyl alcohol, 26, 5... 

The second method is azeotropic condensation polymerization of lactic acid, which produces high-molecular weight PLA without using chain-extenders or esterification-promoting adjuvants. This type of polymerization needs high reaction rates and thus uses catalysts however, due to the use of catalysts, the PLA produced by this method is not suitable for some applications, such as medical, since any residual catalyst offers toxicity within the polymer, which is harmful for medical applications. In addition to toxicity, residual catalyst degrades PLA in further processing (39). On the other hand, the level of residual catalyst can be reduced with the use of sulphuric acid (55,56). 

Lactic acid is produced chemically from acetaldehyde, by hydrocyanation, followed by acid hydrolysis of the cyanohydrin (Fig. 8.6 a). The cmde lactic acid is purified via esterification with methanol, distillation of the ester and hydrolysis with recycling of the methanol [34]. Major drawbacks are the production of an equivalent of ammonium sulfate and the cumbersome purification procedure that is required to obtain food-grade lactic acid. 

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