Ethyl lactate, hydrolysis

One of the standard methods for construction of the basic heterocyclic ring was elaborated not long after the turn of the century. Thus, condensation of ethyl lactate with guanidine leads to the imine of the desired ring system (47), possibly by a reaction scheme such as that outlined below. Hydrolysis affords the oxazolidinedione (48). Methylation in the presence of base gives 49. 

Enantiomerically enriched a-hydroxy acetals are interesting synthons and can be transformed to a variety of chiral building blocks such as 1,2-diols, a-hydroxy acids, or 1,2-amino alcohols (Scheme 18.4). Whereas the oxidation to (f )-ethyl lactate was rather difficult and required the protection of the OH group, the reduction could be easily accomplished after hydrolysis of the acetal. No significant racemization was observed. With a boronic acid derivative and a secondary amine as described by Petasis and Zavialov,24 it was also possible to synthesize an amino alcohol with high diastereoselectivity. 

H) Rate of Hydrolysis of Esters. Place 5 ml of water and 5 drops of universal indicator in each of five test tubes. To separate tubes add 10 drops of the ester to be tested, shake and note any change in the pH of the solution. Test ethyl formate, ethyl acetate, ethyl benzoate, ethyl lactate. Immerse in water and heat to 50 . Note the change after ten minutes. Add one drop of 1A sodium hydroxide, note the pH, and again heat for 10 minutes. Tabulate the results. 

The major reaction is oxidative dehydrogenation at the secondary hydroxyl site of lactic acid, but the product pyruvic acid in its free-acid form is unstable to decompose. Thus the substrate was supplied as ethyl ester to protect the carboxyl moiety. Esterification is also of benefit to vapor-phase flow operation in making acids more volatile. Hydrolysis of ethyl lactate gives free pyruvic acid with further decarboxylation to actaldehyde. Ethanol, which is another fragment of ester hydrolysis, eould be either oxidized to acetaldehyde or dehydrated to ethylene at higher temperature above 350°G. The reaction network is summerized in Scheme 1. 

While the reactions ofketenes with enantiopure alcohols usually give modest selectivities [769], the use of (ethyl lactate (isopropyl lactate (/ )-2.1 (R = Me, R = i-Pr) or (R)-pantolactone 1.16 as proton donors has allowed the highly enantioselective formation of 2-arylpropionic esters. A mild hydrolysis (AcOH/HCl or LiOH) leads to the corresponding adds, which are anti-inflammatory drugs [554,923] (Figure 4.8). This method has been extended by Durst and Koh [861, 999] to the synthesis of enantioenriched a-halogenated esters, which are precursors of aminoacids (Figure 4.8). 

Pete and coworkers [1000, 1001] have irradiated a,P-ethylenic esters of enantiopure alcohols, and the intermediate dienols that form are protonated either with AyV-dimethylethanol at -35°C in hexane [1001] or with i-PrOH or terf-BuOH [1000], The chiral auxiliaries are diacetoneglucose 1.48 or (S)-ethyl lactate 2.1 (R = Me, R = Et), or better yet the corresponding add (Figure 4.9). The cleavage of the chiral auxiliary is accomplished by treatment with PhCH20H/Ti(0/-Pr)4 or by mild hydrolysis. After the subsequent reaction with diazomethane, nonracemic benzyl or methyl a-alkylated-P.y-unsaturated esters are obtained with high enantiomeric excesses (Figure 4.9). 

It is clear that a restricted orientation of the dienophile is crucial to the success of the asymmetric Diels-Alder reaction. A good method to lock the conformation is to use an auxiliary containing a carbonyl group, such that the two carbonyl groups of the dienophile can chelate to a Lewis acid. Thus, high levels of diastereofacial selectivity can be achieved in Diels-Alder reactions of the acrylates of ethyl lactate or of pantolactone, in the presence of the Lewis acid TICU (3.91). The adduct 124 is formed almost exclusively (93 7 ratio of diastereomers) using butadiene and the acrylate of (/f)-pantolactone and can be purified easily by crystallization. Simple hydrolysis gives enantiomerically pure carboxylic acid 125. In such chelated systems, the metal is co-ordinated anti to the alkene of the dienophile and the acrylate therefore adopts the s-cis conformation 126. 

Regarding other uses reported, ethyl lactate is being currently explored as green reaction medium for chemical synthesis and used as a route to produce 1,2-propanediol, chemical compound mainly used for the production of unsaturated polyester resins, which is actually produced from non-renewable sources on industrial scale. Moreover, as already pointed out, ethyl lactate production and subsequent hydrolysis can be used to obtain high-purity lactic acid. ... 

Active methylene groups undergo Mitsunobu reactions with alcohols. Thus, when ethyl cyanoacetate is reacted with ethyl L-lactate, diethyl 2-cyano-3-methylsuccinate (113) is formed in 61% yield [42]. Acidic hydrolysis furnishes (5)-( — )-methylsuccinic acid (114) in 29% yield with an optical purity of 99% [43]. 

Tosyl lactates 120 are readily prepared by treating the corresponding L-lactic acid ester with />-toluenesulfonyl chloride in the presence of either pyridine [45] or triethylamine [30]. Ethyl ester 120b has been prepared on a multi-kilogram scale in nearly 97% yield [46]. Careful hydrolysis of the ester furnishes ( S)-( — )-2-tosyloxypropionic acid 121. 

The asymmetric center of 120b can be inverted with carbon nucleophiles, as demonstrated by the synthesis of 1-ethyl ( S)-( — )-2-methylsuccinate (145) [52]. The reaction of 120b with sodium di- r -butylmalonate gives triester 144 with total inversion of configuration. Hydrolysis and decarboxylation furnishes the monoacid 145 (99% ee) in 54% overall yield from ethyl L-lactate. 

The synthesis of all three sugars proceeds through a common intermediate, L-/yxo-1,4-lactone (393). Lactates 377 or 391 are converted to the lithio derivative 389 by alkaline hydrolysis with lithium hydroxide. The carboxyl ate is then activated with DPP A and reacted with the sodium salt of ethyl isocyanoacetate to give oxazole 390 (Scheme 53). 

Hydrolysis reaction of ethyl d- and L-lactates (EtLa)s catalyzed by protease were studied EtLLa was consumed a little faster than EtDLa. The mechanism of the protease-catalyzed oligomerization was similar to that of lipase (as seen in Figs. 3 and 4), but in an L-selective manner the enantioselection is governed by the deacylation step. 

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