A-Chloro acids

The conversion of an aliphatic carboxylic acid into the a-bromo- (or a-chloro ) acid by treatment with bromine (or chlorine) in the presence of a catal3rtic amount of phosphorus tribromide (or trichloride) or of red phosphorus is known as the Hell-Volhard-Zelinsky reaction. The procedure probably involves the intermediate formation of the acyl halide, since it is known that halogens react more rapidly with acyl haUdes than with the acids themselves ... 

During a relatively long period, the condensation of rhodanines with aldehydes was developed, especially by Andreasch s group (78-87). Finally, Holmberg (88, 89) described the best method to obtain rhodanines the condensation of ammonium dithiocarbamate with a sodium or potassium salt of an a-chloro acid. 

Entry a-Chloro Acid Scale (mole) Temperature (°) Yield" (%)... 

One example of an a -chloro acid chloride conversion to a diazetidinone has been reported (Scheme 74) (63JCS674). Similarly, oxalyl chloride and di-f-butylhydrazine give 1,2-di-f-butyl-l,2-diazetidine-3,4-dione which is moderately stable in absence of air. The corresponding diisopropyl is much less stable (67JOC2360). 

Chlorohydnns, preparation from a-chloro acids, 66, 161 (S )-2-Chloro-3-methylbutan-l-ol, 66, 164... 

Lithium diisopropylamide, 163 Phenyl azide-Aluminum chloride, 240 Halo carbonyl compounds (see also Unsaturated carbonyl compounds) a-Chloro acids Sodium nitrite, 282 a-Halo aldehydes and ketones... 

Substituted thiazolidin-4-ones (449) are easily prepared by the reaction between chloracetic acid, or its derivatives (447), and a thiourea, a thiosemicarbazide, or a mono-or di-thiocarbamate (448 Scheme 255). The same a-chloro acid derivatives react with metallic thiocyanates yielding an intermediate (450), the cyclization of which gives a 2-iminothiazolidin-4-one (451). In these reactions a -chloracetic acid may be replaced by... 

Oxazolidinones are usually obtained by reaction between a hydroxylamine and a chloro acid chloride followed by cyclisatlon... 

For thermally induced [2 + 2] cycloadditions, the concerted mechanism is operative only in particular cases, such as in the reactions between an alkene or alkyne and a ketene. The ketene can be generated directly in the reaction mixture from the appropriate acid chloride with triethylamine. The cycloaddition reaction is stereospecific and occurs exclusively in a cis fashion. Although the intermolecular cycloaddition with ketene itself proceeds in poor yields due to the propensity of the unsubstituted ketene to undergo dimerization, it is quite an efficient reaction with ketenes containing electron-withdrawing substituents. Usually, a-chloro ketenes are employed as reagents formed in situ from the corresponding a-chloro acid chlorides. Typical examples are represented in the preparation of cycloadducts such as 378 and 379 (Scheme 2.127). The latter cycloadduct, prepared in modest yield (ca. 20%),... 

Diazo ketones give a-chloro ketones on treatment with hydrogen chloride (equation 9). Diazotiza-tion of a-amino acids in the presence of an excess of chloride gives a-chloro acids (Scheme 11). The configurational identity of the amino acids is lost with the achiral diazo intermediate. The reaction becomes useful in cases where the amino acid is easily available and the chloride is not. 

Another class of amphoteric are the N-alkyl amino propionates having the structure R-NHCH2CH2COOH. The NH group is reactive and can react with another acid molecule (e.g., acrylic) to form an amino dipropionate R-N(CH2CH2COOH)2. An alkyl imidazoline-based product can also be produced by reacting alkyl imidozo-line with a chloro acid, but the imidazoHne ring will break down during formation of the amphoteric. 

Finally, free a-chloro acids have been prepared in high enantiomeric excess by chlorination of silyl keteneacetals using D-(+)-glucose diacetonide as chiral auxiliary (refs. 13,14). The most outstanding features of this very efficient chiral auxiliary are the cheapness, and the easy hydrolysis of the final a-halo esters, that allows the removal of the chiral auxiliary under nonracemising conditions moreover, this compounds is non toxic and is commercially available. 

Acid chlorides up to C8 give good yields of a-chloro acid too great concentrations of chlorine decrease the yields.537... 

S02C12 does not chlorinate aliphatic acids or acid chlorides appreciably in the dark and in the absence of catalysts if, however, a halogen carrier is introduced, the a-chloro acids are formed. 

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