FIELD

The present disclosure relates to a new one-pot, stereospecific, process for the manufacture of (S)-2-chloropropionic acid alkyl ester starting from (L)-alkyl lactate using stoichiometric thionyl chloride and catalytic lewis base ionic liquid resulting in high overall yield with no epimerization and no ester hydrolysis.

BACKGROUND

(S)-2-chloropropionic acid methyl ester is a potential intermediate compound in the manufacture of the agrochemical phenoxy herbicide, mecoprop-p, which is the active (R)-enantiomer of the racemic herbicide mecoprop, 2-(4-chloro-2-methylphenoxy)propanoic acid.

A direct preparation of ethyl 2-chloropro-pionate by chlorinating ethyl lactate with thionyl chloride was first described by Frankland and Garner in J. Chem. Soc. (1914) v105, 1101-1115 in a two stage process. The first stage is the reaction of ethyl lactate with thionyl chloride to form a chlorosulphinate and the second stage is the thermal decomposition of the chlorosulphinate obtained above, by heating in the presence of pyridine hydrochloride as a catalyst, to give the desired ethyl 2-chloropropionate. This reference presented numerous difficulties: Firstly, there is vigorous uncontrolled evolution of HCl gas which is not amenable to industrial production due to safety concerns. Secondly, various side reactions occurred leading to the formation of undesirable byproducts which require distillation for purification which lowers the yield of the desired ethyl 2-chloropropionate. Thirdly, when applied to an isomerically pure starting material, (R) or (S)-ethyl lactate, the use of pyridine hydro-chloride as a catalyst caused partial racemisation of the ethyl 2-chloropropionate to below 80% ee, rendering it unusable for the production of enantiomerically pure agrochemicals, such as (R)-2-(4-chloro-2-methylphenoxy)propionic acid in accordance with the process de-scribed in French Pat. No. 1,479,271.

In 1979 Rhone Poulenc published an improvement on the above process for making (S)-2-chloropropionic acid methyl ester from L-methyl lactate (U.S. Pat. No. 4,334,083). According to the inventors, in their process, the evolution of hydrogen chloride gas was better controlled, byproduct production was reduced and racemization of the resultant (R) or (S)-2-chloropropionic acid methyl ester when starting with (S) or (R) methyl lactate respectively, was minimized. This was achieved by: (a). gradually adding a mixture of methyl lactate in thionyl chloride to a mixture of thionyl chloride and pyridine or dimethylformamide (organic base); (b). Using a small amount of pyridine (between 0.1 and 1.0 percent by weight) to minimize racemization; (c). using a temperature between 15 to 65° C. during the first stage (d). carrying out a slow addition (3 to 5) hours to add the thionyl chloride in the first stage; (e). using a lower temperature of less than 80° C. and a long total time of 4 to 10 hours in stage two.

Although this process improved on Frankland and Garner's earlier process, it had long reaction times, inconsistent racemization, and required distillation and its commercial utility was eclipsed by the use of enzymes to stereospecifically resolving racemic mixtures of 2-chloropropionic acid as described in EP0179603 and EP0257716 (1988) to give the desired (S)-2-chloropropionic acid and recycling the (R) acid isomer by epimerization to the racemic mixture for further resolution. However, the enzymatic process used commercially today, is multi-stepped with recycles of starting material required, is energy inefficient and requires large volume dilutions that are not consistent with environmentally sensitive green manufacture.

Consequently, there still exists a need to produce (S)-2-chloropropionic acid methyl ester, in high epimeric excess (ee) using a single step reaction, in a high yield and purity which does not require distillation, that has a low environmental impact and uses no solvents, for use as an intermediate in the production of agrochemicals.

BRIEF SUMMARY

The present invention describes a rapid, single step reaction of L-methyl lactate and thionyl chloride in the presence of a catalytic quantity of a lewis base ionic liquid.

In some embodiments, the lewis base ionic liquid is 1,1,3,3-tetramethylguanidinium acetate.

In some aspects, the reaction can be carried out by reacting one molar equivalent of thionyl chloride and L-methyl lactate in the presence of 0.1-1.0 percent, weight to weight of L-methyl lactate, of the lewis base ionic liquid, 1,1,3,3-tetramethylguanidinium acetate.

In some aspects, the total reaction is completed within 2 hours while still maintaining a controlled evolution of hydrochloric acid and sulfur dioxide.

In some aspects, the resultant (S)-chloropropionic acid methyl lactate requires no additional purification or fractional distillation prior to use as an intermediate in the production of (R)-2-(4-chloro-2-methylphenoxy)propionic (also known as mecoprop-p) herbicide.

