Halopropionic acids

Other Syntheses. Acryhc acid and other unsaturated compounds can also be made by a number of classical elimination reactions. Acrylates have been obtained from the thermal dehydration of hydracryhc acid (3-hydroxypropanoic acid [503-66-2]) (84), from the dehydrohalogenation of 3-halopropionic acid derivatives (85), and from the reduction of dihalopropionates (2). These studies, together with the related characterization and chemical investigations, contributed significantly to the development of commercial organic chemistry. 

Oxo-3,4-dihydro-2//-pyrido[l,2-ci]pyrimidines (142) and their hydrogen halide salts can be prepared by reacting 2-aminopyridine or methyl-substituted 2-aminopyridines with alkyl 3-halopropionates,20,196-200 3-halopropionic acids,200-203 or alkyl acrylates18,20 197,204 205... 

Halopropionic acid derivatives are readily accessible from lactic acid via its mesylate. Thus, treatment of 156a with AICI3 affords methyl (i )-2-chloropropionate (162) with 88% ee [59]. Reaction of 156a with KF in formamide produces methyl (R)-2-fluoropropionate (163) (96% ee). The use of formamide as solvent not only increases the reaction rate but also favors Sn2 reaction due to its high polarizability. The ti ji is approximately 30 min, and reaction is complete in 3 h [57]. (R)-2-Fluoropropionic acid is prepared from 163 by transesterification with formic acid. Amberlyst A-26 (F ) can be used as an alternate fluoride source in the conversion of mesyl lactates to chiral a-fluoroesters. This polymer-supported reagent produces clean Sn2 reactions [60]. 

The synthesis of phenoxypropionate herbicides form 2-halopropionic acids, based on the specific esterification of S-isomers with butanol catalyzed by porcine pancreatic lipase (Hasan et al. 2006)... 

Additions. Halogens, hydrogen haUdes, and hydrogen cyanide readily add to acryUc acid to give the 2,3-dihalopropionate, 3-halopropionate, and 3-cyanopropionate, respectively (21). 

Azetidones (p-lactams) are generally obtained in high yield from (3-halopropion-amides (Table 5.18) and the low yield from the reaction of N-phenyl (3-chloropropi-onamide can be reconciled with the isolation of A-phenyl acrylamide in 58% yield [34]. The unwanted elimination reaction can be obviated by conducting the cyclization in a soliddiquid system under high dilution [35, 36]. Azetidones are also formed by a predominant intramolecular cyclization of intermolecular dimerization to yield piperazine-2,5-diones, or intramolecular alkylation to yield aziridones. Aone-pot formation of azetidones in 45-58% yield from the amine and P-bromocarboxylic acid chloride has also been reported [38]. 

An interesting pyrolysis product of 3-chloro-2,2-bis (chloromethyl) propionic acid at 200-220 °C is 1,1-bis (chloromethyl)ethene153. This reaction may well be associated with the five-membered dehydrochlorination process of a-halopropionic acids146,147. In this respect, the HC1 elimination may be considered to proceed through a mechanism involving a six-membered transition state as described in equation 69. 

Aiyl esters such as those of a-halopropionic and a-halobutyric acids undergo cycloalkylation reactions, probably via preliminary Fries rearrangement to 3-halohydroxy ketones, giving the corresponding substituted indanones (equation 98). ... 

It has been published and patented that mPEG-propionic acid can be obtained by nucleophilic displacement reaction of mPEG-alkoxide with ethyl 3-bromopropionate or with halogenated 3-halopropionate substrates [78,79]. However, it was later indicated that the first method does not afford the required acid but the elimination product, due to the acid-base reaction of the hydrogen in the position a- to the carboxylic group [74]. 

---