Optical purity of lactic acid

Table 1 summarises all the methods for the determination of the optical purity of lactic acid as well as their respective advantages and drawbacks. 

Table 1. Summary of the methods for determining the optical purity of lactic acid...

In order to meet market needs, Rhone-Poulenc has had to produce very high optical purity D-lactic acid on one hand and esterify it to isobutyl lactate on the other. This product is then transformed to the corresponding a-chloropropionate. The detection limit of the minority enantiomer in the three compounds must be as low as possible (0.1% for lactic acid and 0.5% for both esters). 

This technique played a big role in the synthesis of all possible isomeric forms of lactic acid in which the methyl contains all three hydrogen isotopes and the hydrogen at C-2 can be either H, 2H or 3H. Each of the three structures, CH3CHOHCOOH, CH3C2HOHCOOH and CH3C3HOHCOOH, contains two chiral centers when the methyl is CH2H3H. Each structure thus exists in four forms, for a total of 12 isomers. They can all be prepared in substantial amounts and with high optical purity [133]. 

Chiral methyl chiral lactic acid (5). This labeled molecule, useful for study of stereospecificity of enzymic reactions, has been prepared in a way that allows for synthesis of all 12 possible isomers. One key step is the stereospecific debromination of 1, accomplished by conversion to the vinyl-palladium cr-complex 2 followed by cleavage with CF3COOT to give the tritium-labeled 3. The next step is the catalytic deuteration of 3, accomplished with a rhodium(I) catalyst complexed with the ligands norbornadiene and (R)-l,2-bis(diphenylphosphino)propane. This reaction gives 4 with an optical purity of 81%. The product is hydolyzed to 5, which is obtained optically pure by cr3rstallization. 

Table 3. Recap of the methods for determination of the optical purity of methyl and isobutyl esters of lactic acid.

A sample of (5)-(+)-lactic acid was found to have an optical purity of 72%. How much R isomer is present in the sample ... 

Acetylthio)propionic acid (102) is obtained in 40% yield when a mixture of ( S)-lactic acid and thioacetic acid is added to the preformed DIAD/PhsP adduct in THF at 0 °C [36]. Unfortunately, the optical purity of the product is only 71%. The loss of optical integrity may be attributed to competitive formation of a-lactone 103 as a result of intramolecular Sn2 attack of the carboxyl on the activated hydroxyl. A second Sn2 reaction of thioacetic acid... 

Benzylation of lactic acid esters can be accomplished by two methods. Treatment of methyl or ethyl L-lactate with benzyl bromide and silver oxide provides the corresponding (5)-2-ben-zyloxypropionates 271 with high optical purity [92,93]. Use of standard basic conditions (NaH, DMF) results in considerable racemization (50-75% ee). 

Chirality transfer via an ene reaction is a useful method for preparing enantiomerically pure substances. This strategy is elegantly demonstrated by the use of lactic acid as the chiral source for adducts 415, which are obtained with high optical purity [128] (Scheme 57). 

Over the past several decades, polylactide - i.e. poly(lactic acid) (PLA) - and its copolymers have attracted significant attention in environmental, biomedical, and pharmaceutical applications as well as alternatives to petro-based polymers [1-18], Plant-derived carbohydrates such as glucose, which is derived from corn, are most frequently used as raw materials of PLA. Among their applications as alternatives to petro-based polymers, packaging applications are the primary ones. Poly(lactic acid)s can be synthesized either by direct polycondensation of lactic acid (lUPAC name 2-hydroxypropanoic acid) or by ring-opening polymerization (ROP) of lactide (LA) (lUPAC name 3,6-dimethyl-l,4-dioxane-2,5-dione). Lactic acid is optically active and has two enantiomeric forms, that is, L- and D- (S- and R-). Lactide is a cyclic dimer of lactic acid that has three possible stereoisomers (i) L-lactide (LLA), which is composed of two L-lactic acids, (ii) D-lactide (DLA), which is composed of two D-lactic acids, and (iii) meso-lactide (MLA), which is composed of an L-lactic acid and a D-lactic acid. Due to the two enantiomeric forms of lactic acids, their homopolymers are stereoisomeric and their crystallizability, physical properties, and processability depend on their tacticity, optical purity, and molecular weight the latter two are dominant factors. 

This chapter focuses on the microbial fermentation process for lactic acid production. The first commercial operation was set up by Avery in the USA in 1881. Microbes contain enzyme(s) called LDH which can convert pyruvic acid to lactic acid. Depending on the particular microbe and the specificity of its LDH, the lactic acid fermentation process can produce rather pure d-LA or l-LA with high optical purity, or a mixture of them with low optical purity. Genetic engineering tools can be used to knockout the d-LDH gene(s) in the production strain to improve the optical purity of its l-LA fermentation process. 

Di Lorenzo, M.L., Rubino, P., Luijkx, R., and Helou, M. (2014) Influence of chain structure on crystal polymorphism of poly(lactic acid). Part 1 effect of optical purity of the monomer. Colloid Polym. Sci., 292, 399 -409. 

Commercial PLA is a blend of PLLA and PDLA or copolymer PDLLA, obtained by the polymerization of LLA and DLLA, respectively [1]. Many important properties of PLA are controlled by the ratio of d- to L-enantiomers used and the sequence of arrangement of the enantiomers in the polymers. PLLA constitutes the main fraction of PLA derived from renewable sources since the majority of lactic acid obtained from biological sources exists as LLA. PLA with PLLA content higher than 90% tends to be crystalline while that with lower optical purity is amorphous. The melting temperature (Tm), glass transition temperature (Tg), and crystallinity of PLA decrease with decreasing amounts of PLLA [2-5]. 

F. Matsuoka, K. Hashimoto, Poly(lactic acid)-type conjugate staple fibers with good biodegradabihty and heat-bonding properties consisting of two types of lactic acid polymers with different optical purity and nonwoven fabrics therefrom and manufacture thereof, JP 2001049533,2001, CAN 134 179858. 

The commercial forms of PLA are the homopolymer poly(L-Lactide) (L-PLA or PLLA) and the copolymer poly(D,L-Lactide) (D,L-PLA or PDLLA), which are produced from L-lactide and D,L-lactide, respectively. The L-isomer constitutes the main fraction of PLA derived from renewable sources, since the majority of lactic acid from biological sources exists in this form [43]. Polylactides (PLAs) exhibit different properties depending on the D/L unit radio and sequence distribution. Generally, the crystallinity of PLLA and PDLA decreases with increasing racemic content. PLA polymers with an L-content >90% tend to be semicrystalline, while those with a lower optical purity are generally amorphous [43-45]. 

Chemical synthesis of lactic acid from lactonitrile is the major alternative process for manufacture in competition with fermentation lactic add. In 1995, synthetic lactic acid accounted for about 50 % of the total world lactic acid production (Litchfield 1996). The advantage of the chemical synthesis route is the ease of obtaining a highly purified lactic acid which is required for many industrial products. The synthetic lactic acid is a racemic mixture (DL), whereas fermentation lactic acid may be selectively D(—) or L(-t) or DL depending on the organism catalyzing the conversion. Controlled optical purity as well as... 

Poly-/-lactic acid has been extensively studied. By cationic polymerization of Mactide, a highly crystalline isotactic polymer can be obtained with Fridel-Craft initiators, or better with zinc or lead oxide ones [130]. The basicity of the catalyst seems to have a substantial effect on the optical purity of the polymer obtained. A stereochemical study is reported by Schultz and Schwaad [131] on a poly-5-lactic acid (LII). 

The other bottleneck for lactic acid production is the operating cost. For example, sterilization is necessary for fermentative production. Hence, microorganisms have an optimal fermentation temperature between 30 2°C (John et al., 2007). Therefore it is difficult to avoid contamination if the medium is not sterilized. Qin et al. (2009) have reported the use of a newly isolated thermophilic strain. Bacillus sp. strain 2 to 6, for the unsterilized fermentative production of L-lactic acid. A high yield (97.3%), productivity (4.37g/L/h), and optical purity of L-lactic acid (99.4%) were obtained in batch and fed-batch open fermentations (Qin et al., 2009). This will help to reduce energy consumption and lower labor costs. Moreover, because of the inhibitory effects of a low pH on cell growth and lactic acid production, CaCOs must be added to maintain a constant pH as a consequence, the regeneration of precipitated calcium lactate is observed (Datta and Henry, 2006). To solve this problem, a sodium lactate-tolerant strain. Bacillus sp. Na-2, was obtained by ion-beam implantation and applied during an L-lactic acid production process (Qin et al., 2010). On the other hand, new processes can be applied to prevent the production of calcium lactate, for example, reverse osmosis, ultrafiltration, electrodialysis, and solvent extraction (Datta and Henry, 2006). 

Chirality is a necessary, but not sufficient, condition for optical activity to be measured. If a solution contains equal numbers of right-handed and left-handed molecules, they rotate the plane-polarized light to an equal and opposite extent, so that no net rotation is observed. This mixture is called a racemate, or racemic mixture (Latin, racemus, a bunch of grapes, because Pasteur first isolated racemic tartaric acid from wine), and is sometimes designated ( ) to indicate that there are equal amounts of (+) and (-) material. Between an equal mixture and a pure enantiomer, every other mixture is also possible. We therefore define the term optical purity or enantiomer excess (ee, 7.2). If we have a mixture of 75 % of the (+)-enantiomer and 25 % of the (-)-enantiomer, we say that the optical purity is 50 %. Although the physical properties, other than optical rotation, of the two enantiomers are identical, it is not invariably the case that a racemate has exactly the same physical properties as a pure enantiomer. For example, either pure enantiomer of lactic acid melts at 53 °C but a racemic mixture melts at 16.4 °C. 

What is interesting, however, is some of the chemistry that is not present. For example, the petrochemical industry does not have a basic feedstock in the five-carbon area and thus we see few products derived from or based on five-carbon chemistry. Optical active compounds are also missing from the petrochemical-derived product list. For example, lactic acid is now made exclusively from glucose, with the reason being that the fermentation route provides stereochemical purity that is difficult to achieve from petrochemical building blocks. 

The use of these asymmetric hydrogenation catalysts gives the C-2 chiral center in about 80% optical purity. The same value would apply also to the chiral methyl. For further purification, a crystallization process was used. The optically impure lactic acid (an oil) was dissolved in an approximately equal volume of boiling diethylether diisopropyl ether, 1 1 on standing at 5°C large, colorless, crystals of optically pure chiral methyl chiral lactic acid, 162, were deposited. The recovery of the purified material was 60%. Because of the inherent relationship between the two chiral centers, optical purity at C-2 guarantees optical purity at C-3. 

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