S-Methyl lactate

Figure 4. Side and top views of the energetically most favorable complexes formed between protonated cinchonidine and methyl pyruvate which would yield (R)-methyl lactate (left) and (S)-methyl lactate (right), respectively, upon hydrogenation. The complexes have been accomodated on a space filling model of platinum (111) surface in order to illustrate the space requirements of the adsorbed complexes. For the sake of clarity, in the side views the carbon atoms of the reactant are marked with a white square and the oxygen atoms with an o. Data taken from ref. [41].

For the Pt/cinchona catalysts only preliminary adsorption studies have been reported [30]. From the fact that in situ modification is possible and that under preparative conditions a constant optical yield is observed we conclude that in this case there is a dynamic equilibrium between cinchona molecules in solution and adsorbed modifier. This is supported by an interesting experiment by Margitfalvi [63] When cinchonine is added to the reaction solution of ethyl pyruvate and a catalyst pre-modified with cinchonidine, the enantiomeric excess changes within a few minutes from (R)- to (S)-methyl lactate, suggesting that the cinchonidine has been replaced on the platinum surface by the excess cinchonine. 

S -Methyl lactate gives a poor ee in hydroboration of acetophenone, but ZnCl2 raises it.322 A molecular orbital method has looked at the enantioselectivities associated with four oxazaborolidine catalysts acting on phenyl methyl ketone.323 0>... 

The hydroboration of acetophenone in the chiral solvent (S)-methyl lactate exhibits moderate enantioselectivities. A six-membered transition state (11) involving the ketone, the borane, and the lactate as the only chiral source is proposed. Molecular modeling explains the experimentally observed enantioselectivities.311... 

Figure 8. Inclusion compound of (S)-methyl lactate by 2. (a) Host-guest hydrogen bonding (A), (b) Sheet structure of dipeptide backbone, (c) Packing (CPK model) of the inclusion compound.

In contrast to dialkylphosphines, which are more difficult to prepare, the reaction of amino alcohols with chlorodialkylphosphines does not provide any problems. Thus, compounds such as Cps-ProNOP 65 are obtained directly from chlorodicyclopentylphosphine and prolinol67 amino alcohols not derived from amino acids have also been successfully used, e.g., (S)-l-(methylamino)-2-propanol [derived from (S)-methyl lactate by aminolysis with methylamine and reduction with lithium aluminum hydride69], which led to Cy-isoAlaNOP 67 by reaction with chlorodicycl ohexylphosphine67. 

Sutherland et al. developed the Template model based on a geometric explanation of enantioselectivity assuming adsorption of the cinchona alkaloid modifier and methyl pyruvate reactant on the surface of a Pt(III) facet such that the alkaloid mochfier is adsorbed by its quinoline ring in such a way that there is a place for adsorption of the pyruvate molecule to form an intermediate active complex which produces, after hydrogenation of the C=0 bond in pyruvate, either the (/ )-(-)-methyl lactate, in the case of using Cnd as modifier, or the (S)-(+)-methyl lactate using Cn as modifier (see the modifier structures in Scheme 5.20.). 

Figure 9 Comparison of the experimental and theoretical IR and VCD spectra of (S)-methyl lactate. The calculation was carried out using density-functional theory and the magnetic-field perturbation theory of VCD intensities. No adjustable parameters were used for the theoretical calculation other than choosing the bandshape for the vibrational transitions.

We ll see in Section 21.3 that carboxylic acids (RCO2H) react with alcohols (R OH) to form esters (RC02R )- Suppose that ( )-lactic acid reacts with CH3OH to form the ester, methyl lactate. What stereochemistry would you expect the product(s) to have What is the relationship of the products ... 

The results collected in Table 5 suggest that hydrocarbon residues, especially aromatic groups, in the solvent are strongly responsible for the interaction with cis-(1+4). The position of the largest hydrocarbon residue apparently determines whether P- or M-[6]-helicene will be formed in excess. Replacement of the methyl group in (S)-ethyl lactate (b) by a phenyl group giving (S)-ethyl mandelate (d), increases the optical yield fivefold. 

The discrimination factors a (a is the ratio of the two sorption equilibrium signals towards both enantiomers) of methyl lactate by R- and S-sensors and the a-1 values to demonstrate the inversion symmetry are shown in Fig. 6, right. The results are in complete accordance with gas chromatographic inves-... 

Fig. 6 Discrimination factors of methyl lactate obtained by five different R- and S-sensors. For the S-sensors, the a values are also shown to demonstrate the inversion symmetry [18]...

The enantiomeric composition of methyl lactate ester mixtures was measured by an array of S- and it-sensors and the data were evaluated by chemo-metric tools (multiple line regression, partial component analysis and principal component regression). The ability to distinguish the enantiomeric composition of various mixtures of N-TFA-Ala-OMe or lactates quantitatively with octyl-Chirasil-Val was demonstrated [18]. 

By crystallization of a mixture of the dipeptide (2) and racemic methyl lactate from methanol, asymmetric recognition occurred to give an inclusion compound that contains the (S)-form of methyl lactate in 89 % ee [20], X-ray crystallographic study of the inclusion compound was able to elucidate that the dipeptide molecules... 

In 2001, Chisholm s group reported a (3-diiminate (BDI) gallium-OSiMe3 complex which was unreactive for LA ROP the authors cited substrate binding as the limiting step [76]. Recently, a gallium alkoxide initiator (11) has been reported as an efficient polymerization initiator [72]. The dimeric complex was formed by reaction of GaMe3 with (A)-methyl lactate (Fig. 15). 

Fig. 9 Comparison of VCD spectra for the S form of (a) propylene oxide, (b) glycidol, (c) lactic acid, and (d) methyl lactate in aqueous solutions. The chirality transfer spectral windows are indicated with dotted lines. Adapted with permission from [132]. Copyright (2009) American Institute of Physics...

A variety of alcohols, for example, 2-octanol (182,183), (-)-2-butanol (184), (+)-3-methyl-2-butanol (185), (-)-menthol (186), (S)-ethyl lactate (187), (R)-l-phenylethanol (188), etc., have been used. Several different sets... 

Figure 1.13 GC analysis of organic acid methyl esters in a) standard solution, b) Chardonnay wine, c) Asti sparkling wine. 1. methyl lactate, 2. dimethyl succinate, 3. dimethyl maleate (i.s.), 4. dimethyl malate, 5. dimethyl tartrate, 6. trimethyl citrate. Chromatographic conditions poly(ethylene) glycol fused silica capillary column (30m x 0,25mm 0.25 xm), injector and detector temperature 250°C, flame ionization detector. Oven program 2min at 50 °C, from 50 to 200 °C at rate 4°C/min, 200°C isotherm for lOmin (Di Stefano and Bruno, 1983)...

In some examples, the stereochemistry of radical reactions was controlled by chiral carbohydrate auxiliaries. As a radical counterpart to the ionic conjugate additions discussed above, Garner et al. [169] prepared carbohydrate linked radicals that were reacted with a,P-unsaturated esters. The radical precursor, the carboxylic acid 256, generated by the addition of ( Sj-methyl lactate to tri-O-benzyl-D-glucal and subsequent ester hydrolysis, was decarboxylated by Barton s procedure (Scheme 10.84) [170]. Trapping of the chiral radical 258 with methyl acrylate furnished the saturated ester 259 in 61% yield and with high diastereoselectivity (11 1). The auxiliary caused a preferential addition to the si-facQ of radical 258, probably due to entropic effects. The ester 259 was transformed in acceptable yield to the y-butyrolactone 261 by reductive removal of the thiopyridyl group followed by acid hydrolysis. 

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). 

This method of preparation is suitable for producing primary alkyl lactates but is unsatisfactory for S-methallyl lactate because the strong mineral acid catalyzes the rearrangement of methallyl alcohol to isobutyraldehyde. Methyl lactate can be made conveniently (80-85% yield) by heating 1 mole of lactic acid condensation polymer with 2.5-5 moles of methanol and a small quantity of sulfuric acid at 100° for 1-4 hours in a heavy-walled bottle, such as is used for catalytic hydrogenation with a platinum catalyst. 

Krishna G., Rangaiah, G.R and Lakshminarayanan, S. (2013) Modehng and Optimization of Reactive HiGee Stripper-Membrane Process for Methyl Lactate Hydrolysis. Ind. Eng. Chem. Res., 52,7795-7802. 

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