4- Chlorohexanoic acid

Homolytic cleavage of oxaziridines by ferrous salts, already described by Emmons, is a useful source of alkyl radicals. From oxaziridine 28, easily accessible from cyclohexanone and Af-chloromethylamine, on the action of ferrous salt, reaction products of radical 29 are obtained In the presence of FeCl2 oj-chlorohexanoic acid methylamide (30) is formed quantitatively in the absence of reaction partners, dimerization occurs to 31. As shown in a very careful investigation by Hawkins in the case of the N-cyclohexyl compound, the dicarboxylic acid derivative is accompanied by appreciable quantities of branched-acid derivatives, formed by a radical rearrangement 29 -> 32. The radical 29 adds to pyridine and gives rise, after rearomatization, to the formation of 70-80% of 2- and 4-substituted pyridine (33). ... 

Benzoylamino)-2-chlorohexanoic acid 539 6-(Benzoylamino)hexanoic acid (35.3 g, 0.15 mole) and finely powdered iodine (0.5 g) are dissolved in S02C12 (70 ml) and heated at 60-65° in a water-bath until the gas evolution slackens. The mixture is then brought slowly (60-90 min) to the b.p., after which the excess of S02C12 is distilled off and the residual crude 6-(benzoylamino)-2-chlorohexanoic acid is washed with water. This material (yield 96-97.5 %) can be used without further purification for the preparation of lysine. 

Another way to statin side chains, via the intermediate syn-(i K,5,S )-6-chloro-hexanoate, employs regioselective and (K)-specific reduction with alcohol dehydrogenase (ADH) from Lactobacillus brevis to yield the intermediate (5S)-6-chloro-3-ketohexanoate from the 3,5-diketo acid (Wolberg, 2001) (Figure 13.16). Further reduction of (5S)-6-chloro-3-ketohexanoate to syn-(3R,5S)-6-chlorohexanoate is afforded chemically with NaBH4/B(OMe)Et2. 

Interestingly ketones can be carbonylated. Reaction of cyclohexanone with CO in MeOH using PdCh and CuCb as catalysts under mild conditions afforded dimethyl pimelate (474) and methyl 6-chlorohexanoate (475) in good yields. Mechanism of the carbonylation is not clear. Dimethyl pimelate (474) is formed by methanolysis (retro-Dieckmann reaction) of methyl cyclohexanonecarboxylate (478) promoted by CuCF and acid. Methyl cyclohexanonecarboxylate (478) may be formed by methoxypalladation of the enolate 476 to form Pd enolate 477, followed by CO insertion. Chlorination of cyclohexanone with CuCl2 gives 2-chlorocyclohexanone 480 which is converted to 475 [197]. 

Halogenated PHAs. Several halogenated PHAs were obtained when certain bacterial species (P. oleovorans, P. putida) were cultured in media containing chlorinated, brominated or fluorinated compounds. A copolyester containing (R)-3-hydroxyoctanoate, (P)-3-hydroxy-8-chlorooctanoate, (P)-3-hydroxyhexanoate and (/ )-3-hydroxy-6-chlorohexanoate was synthesized when a culture of P. oleovorans was fed with octane and 1-chlorooctane as carbon sources (Doi and Abe 1990). Additionally, PHAs containing brominated monomers were produced by P. oleovorans when it was cultured in media containing mixtures of n-alkanoic acids (octanoic and nonanoic acids) and co-bromoalkanoic acids (Kim et al. 1992). 

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