A-Chloro carboxylic acids

Nitroethane may be similarly obtained from sodium a chloropropionate. This is a general reaction for a chloro carboxylic acids, but in practice only monochloroacetic acid and a chloropropionic acid are readily available. 

The a-bromo or a-chloro carboxylic acids 2 are versatile intermediates for further synthetic transformations. For example they can be converted into a-hydroxy carboxylic acids by reaction with water by reaction with cyanide a-cyanocarboxylic acids 7 are obtained, which can be further converted to... 

The presence of the carboxyl group (—CO2H) in this molecule means that the compound is a carboxylic acid. As well, a Cl atom has replaced one H atom. This compound is a chloroalkane. The compound is a chloro carboxylic acid. 

The synthetic application of the a-chloro aldehydes has been demonstrated by the preparation of a variety of important chiral building blocks (Scheme 2.35) [26b]. The a-chloro aldehydes could be reduced to the corresponding optically active a-chloro alcohols in more than 90% yield, maintaining the enantiomeric excess by using NaBFU. It was also shown that optically active 2-aminobutanol - a key intermediate in the synthesis of the tuberculostatic, ethambutol - could be obtained in high yields by standard transformations from 2-chlorobutanol. Furthermore, the synthesis of an optically active terminal epoxide was demonstrated. The 2-chloro aldehydes could also be oxidized to a-chloro carboxylic acids in high yields without loss of optical purity, and further transformations were also presented. 

Note Most of the available examples in this subcategory involve the somewhat specialized condensation of a-aminonitriles (as four-atom synthons)with oxalyl chloride, operating not as a dihalogenoethane derivative (as exemplified previously) but as an a-chloro carboxylic acid derivative. 

B. Alkylation of (LIX) with halo carboxylic acids or esters (preferably chloroformic acid or a-chloro carboxylic acids) followed by treatment of the intermediate (LXVII) with alkali which causes a mercapto carboxylic acid to be split off. The 2-(hydroxyalkyl) isothiocyanate (LXVI) formed cyclizes into (LXI) 314, 328). 

Pyridine-N-oxide [1, 966]. a-Bromo and a-chloro carboxylic acids are oxidatively decarboxylated by treatment with pyridine-N-oxide (4 equiv.) in refluxing benzene or toluene.3 Cohen et at. note that, since pivalic acid is completely inert to pyridine-N-oxide, an u-hydrogen atom appears to be essential, for example in the reaction of phenylacetic acid. They suggest that an a-pyridinium ion is an intermediate ... 

An alternative method for the formation of enantioenriched a-chloroesters, using A-heterocyclic carbene catalysts, was reported by Reynolds and Rovis (Scheme 13.14) [34]. In a similar mechanism to that presented in Scheme 13.12, initial attack of the carbene to the aldehyde and loss of HCl generated a chiral enolate. Asymmetric protonation of this enolate followed by displacement of the azolium species by a phenol produced enantiopure a-chloroesters. In contrast to the approach to chiral a-chloroesters presented in Scheme 13.13, a variety of aryl esters can be incorporated into the product by using different aryl alcohols (ArOH). Additionally, a carbon-chlorine bond is not formed in this reaction. Rather the introduction of a stereocenter in the chlorinated products is achieved via asymmetric protonation. This method was elaborated to use water as the proton/alcohol source to produce chiral a-chloro carboxylic acids (i.e., as in Scheme 13.12) [28]. Moreover, the use of D2O generated chiral a-chloro-a-deutero carboxylic acids. 

Rovis and coworkers used a-halo aldehydes to generate the formal redox ester products in the presence of an N-Ph triazolium salt [77]. This methodology was later extended to the enantioselective formation of phenyl a-chloroesters 96 [78] and a-chloro-carboxylic acids [79] from a,a-dichloro-aldehydes 94 using chiral triazolium salt 95 (Scheme 18.16). Consistent with the simultaneous observations by Bode and coworkers, a nucleophilic co-catalyst was necessary for the formation of amides [80]. An a-chloroamide could be synthesized in good enantioselectivity (80% ee) by the use of chiral triazolium salt 95. 

Type A (S—C—N + C—C) Syntheses.—A further variety of 2-iminothiazolidin-4-ones has been prepared, mainly by Indian workers, by the well-established procedure of allowing an a-chloro-carboxylic acid (usually chloroacetic acid) to react with a iV-mono- or AA -di-substituted thiourea. > Condensation of... 

Chloro-8-nitroquinoline stirred 24 hrs. at 25° with excess 99%-hydrazine hydrate and dimethyl sulfoxide 7-hydrazinoquinoline. Y 49% 53% as the hydrochloride. A. x lbert and G. Catterall, Soc. (C) 1967, 1533 -bydrazino- from a-chloro-carboxylic acids, in methanol, inversion of configuration, s. M. Sletzin-ger et al., J. Med. Chem. 11, 261 (1968). 

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