Chloropropionate

Batchwise operated multipurpose plants are per defmitionem the vehicle for the production of fine chemicals. There are, however, a few examples of fine chemicals produced ia dedicated, coatiauous plants. These can be advantageous if the raw materials or products are gaseous or Hquid rather than soHd, if the reaction is strongly exothermic or endothermic or otherwise hazardous, and if the requirement for the product warrants a continued capacity utilization. Some fine chemicals produced by continuous processes are methyl 4-chloroacetoacetate [32807-28-6] C H CIO [32807-28-6], and malononittile [109-77-3] C2H2N2, made by Lonza dimethyl acetonedicarboxylate [1830-54-2] made by Ube and L-2-chloropropionic acid [107-94-8] C2H C102, produced by Zeneca. 

Among other mercaptocarboxyhc acids, the mercaptopropionic acids have undergone a promising development. Thiolactic acid or 2-mercaptopropionic acid [79 2-5] HSCH(CH2)COOH, is manufactured by usiag 2-chloropropionic acid [598-78-7]. 3-Mercaptopropionic acid [107-96-0] HSCH2CH2COOH, competes with thioglycohc acid ia plastic additives or as modifiers ia various polymers. Mercaptopropionic acid is... 

Alkyl 2-chloropropionates react v/ith nltroaromadc compounds on treatment v/ith base to give alkyl 2-f4-nitroaryl propionates in good yield fEq 9 26 ... 

The resolution of racemic ethyl 2-chloropropionate with aliphatic and aromatic amines using Candida cylindracea lipase (CCL) [28] was one of the first examples that showed the possibilities of this kind of processes for the resolution of racemic esters or the preparation of chiral amides in benign conditions. Normally, in these enzymatic aminolysis reactions the enzyme is selective toward the (S)-isomer of the ester. Recently, the resolution ofthis ester has been carried out through a dynamic kinetic resolution (DKR) via aminolysis catalyzed by encapsulated CCL in the presence of triphenylphosphonium chloride immobilized on Merrifield resin (Scheme 7.13). This process has allowed the preparation of (S)-amides with high isolated yields and good enantiomeric excesses [29]. 

Ue 7.13 Dynamic kinetic resolution of 2-Chloropropionate by enzymatic aminolysis. 

The reductase from Burkholderia sp. strain WS produces (5)-2-chloropropionate from 2-chloroacrylate (Kurata et al. 2005). 

The degradation of 2- and 3-chloroacrylate displays novel features. The degradation of 2-chloro-acrylate by Burkholderia sp. strain WS is initiated by a 2-haloacrylate reductase with the formation of (5)-2-chloropropionate that undergoes dehalogenation to (J )-lactate (Kurata et al. 2005). The degradation of 1,3-dichloropropene by Pseudomonas pavonaceae (cichorii) strain 170 involves a series of steps by which tra 5 -3-chloroacrylate is formed (Poelarends et al. 1998). This was degraded... 

CjHgO Dimethyl ether CaHgCtOj 2-Chloropropionic acid... 

The selective inclusion properties of 40 (Table 6) offer several possibilities of compound separation which are of interest in analytics and for preparation purposes37). The separation of methanol from a mixture with ethanol, or of propionic aldehyde from propionic acid, or of 2-chloropropionic acid from propionic acid or lactic acid, etc., are a few examples. 

Alkyl 2-chloropropionates react with nitroaromatic compounds on treatment with base to give alkyl 2-(4-nitroaryl)propionates in good yield (Eq. 9.26).40... 

Recently, the VNS intermediates have been used for further introducing electrophiles. For example, reaction of the enolate of ethyl 2-chloropropionate with nitrobenzene followed by subsequent reaction with an alkylating agent gives a series of esters bearing a quaternary center (Eq. 9.36).63... 

EBrIB ethyl-2-bromoisobutyrate. PEBr l-(bromoethyl) benzene, PECl l-(chloroethyl) benzene, BzBr benzyl bromine, MBrP Methyl-2-bromopro-pionate, MCIP methyl 2-chloropropionate, MClAc methyl chloroacetate... 

It is of interest that reaction of methyl, benzyl, and p-nitrophenyl 2-acetamido-4,6-0-benzylidene-2-deoxy-/3-D-glucopyranosides, and also the corresponding methyl a-D-glucopyranoside derivative, with ( )-2-chloropropionic acid gave, in preponderant yields, the respective 3-0-(D-l-carboxyethyl) derivatives257 only from the last-mentioned reaction was a significant amount of the 3-0-(L-l-carboxy-ethyl) derivative isolated. 

In a comparable system, (I ,S)-ibuprofen can be separated by a membrane reactor [83], see Fig. 13.10. The technique comprises a stereo-specific hydrolysis by an enzyme. Subsequently, the enantiomeric ester is extracted into the organic phase on the other side of the membrane. In the system developed by Sepracor Inc., (i )-ibuprofen is selectively hydrolyzed by proteases in a hollow-fiber unit and the (S)-ibuprofen ester can be isolated at 100% yield. This configuration also applies for enantioseparation of other acids such as naproxen and 2-chloropropionic acid. 

To bracket the N1 site of thymine, we will use dichloroacetic acid (Hjcid = 328.4 kcal/mol), difluoroacetic acid (331.0), hydrochloric acid (333.3), pyruvic acid (333.5), 2-bromo-butyric acid (336.8), 2-chloropropionic acid (337.0), and trifluoro-m-cresol (339.3). These acids have acidities in the range that should allow us to bracket the acidity... 

The compound f -2-chloropropionic acid is an important building block for herbicides. Suppose two enzymatic reactions are available for its production ... 

In conclusion, the first reaction yields much more (S)-2-chloropropionic acid, although the enantiomeric ratio of this reaction is much lower. 

Houpis, I.N., Patterson, L.E., Alt, C.A., Rizzo, J.R., Zhang, T.Y. and Haurez, M. S3mthesis of PPAR Agonist via Asymmetric Hydrogenation of a Cinnamic Acid derivative and Stereo-specific Displacement of (S)-2-Chloropropionic Acid. Org. Lett. 2005, 7, 1947-1950. 

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