2-Hydroxy-5-chlorobenzoic acid

Alkyl-1,4-dihydropyridines on reaction with peracids undergo either extensive decomposition or biomimetic oxidation to A-alkylpyridinum salts (98JOC10001). However, A-methoxycarbonyl derivatives of 1,4- and 1,2-dihydro-pyridines (74) and (8a) react with m-CPBA to give the methyl tmns-2- 2>-chlorobenzoyloxy)-3-hydroxy-1,2,3,4-tetrahydropyridine-l-carboxylate (75) and methyl rran.s-2-(3-chlorobenzoyloxy)-3-hydroxy-l,2,3,6-tetrahydropyridine-l-carboxylate (76) in 65% and 66% yield, respectively (nonbiomimetic oxidation). The reaction is related to the interaction of peracids with enol ethers and involves the initial formation of an aminoepoxide, which is opened in situ by m-chlorobenzoic acid regio- and stereoselectively (57JA3234, 93JA7593). 

Other suitable alternate aromatic carboxylic substrates include 3-chlorobenzoic acid, 4-chlorobenzoic and 3-(4-hydroxy-3-methoxyphenyl)-propenoic acid. 

Biological. Reported degradation products by the microorganism Alcaligenes BM-2 for a mixture of polychlorinated biphenyls include monohydroxychlorobiphenyl, 2-hydroxy-6-oxochlorophenylhexa-2,4-dieonic acid, chlorobenzoic acid, chlorobenzoylpropionic acid, chlorophenylacetic acid, and 3-chlorophenyl-2-chloropropenic acid (Yagi and Sudo, 1980). When PCB-1016 was statically incubated in the dark at 25 °C with yeast extract and settled domestic wastewater inoculum, no significant biodegradation was observed. At a concentration of 5 mg/L, percent losses after 7, 14, 21, and 28-d incubation periods were 44, 47, 46, and 48, respectively. At a concentration of 10 mg/L, only 22, 46, 20, and 13% losses were observed after the 7, 14, 21, and 28-d incubation periods, respectively (Tabak et al., 1981). 

Biological. Reported degradation products by the microorganism Alcaligenes BM-2 for a mixture of polychlorinated biphenyls include monohydroxychlorobiphenyl, 2-hydroxy-6-oxochlorophenyl-hexa-2,4-dieonic acid, chlorobenzoic acid, chlorobenzoylpropionic acid, chlorophenylacetic acid, and 3-chlorophenyl-2-chloropropenic acid (Yagi and Sudo, 1980). 

The major by-product in the double hydroxylation reaction is the a-hydroxy ketone F which forms presumably by protiodesilylation of the transient, intermediate epoxide B. In order to exclude tree m-chlorobenzoic acid that might cause this side reaction, MCPBA is purified and added very slowly to the substrate in the presence of excess, finely powdered potassium bicarbonate. In the case of the example presented above, the mechanism presumably is as follows ... 

The oxidation of dienyl enolsilanes to the corresponding a-hydroxy ketones has also been developed and explored by Rubottom.19 For example, diene 37 was cleanly converted to ketone 38 under standard conditions. As expected, high selectivity for oxidation of the more electron-rich double bond was observed. As illustrated by the conversion of 37 to 39, acylation of the crude alcohols was achieved in high yields after removal of w-chlorobenzoic acid and the hexane solvent employed for the oxidation. 

A range of simple analogs of benzoic acid and phenylalanine, easily obtainable from standard chemical suppliers, were chosen as substrates. These included a large number of hydroxy- and dihydroxybenzoic acids, aminoben-zoic acids, nitrobenzoic acids, fluoro-, difluoro-, trifluoro-, tetrafluoro- and pentafluorobenzoic acids, chlorobenzoic acids, iodobenzoic acids, and methoxybenzoic acids. A number of structures other than those with a six-mem-bered aromatic ring were also tried, including pyridinecarboxaldehydes, alicy-clic carboxylic acids, naphthalenecarboxylic acids, furancarboxylic acids, thiophenecarboxylic acids, nitro-, bromo-, and chlorothiophenecarboxyhc acids. 

Treatment of / -methoxyheptachlorostyrene with oleum affords / -hydroxy-heptachlorostyrene. The hydrolysis of a,/ -dimethoxyhexachlorostyrene by means of concentrated sulphuric acid gives a//-/ -ethoxyhexachloroaceto-phenone (Ballester et al., 1980e) total hydrolysis can be accomplished with oleum. It is noteworthy that hydrolytic oxidation results from the direct treatment of dimethoxyhexachlorostyrene with oleum, 4-methoxytetra-chlorobenzoic acid being the product (79). 

Hydroxy-5-chlorobenzoic acid (5-chlorosalicylic acid) (C HcO-Cl) (Values on Vol.3, p.l88)... 

Butanoic acid 2-[l-[(2-hydroxy-4-nitrophenyl)azo]-2-naphthalenyl] hydrazide, B-00605 4-Chlorobenzoic acid [(2-bromo-6-hydroxyphenyl)methylene]hydrazide, C-00068... 

Oxidation oi S-fluoro-t,3-dimethyluraciI by m-chloroperoxybenzoic acid leads to 4-hydroxy-l,3-dimethylimidazoledione m-chlorobenzoate [80] (equadon 72). 

Preparation by reaction of o-chlorobenzoic with 2 -chloro-2-hydroxy-4-methylbenzo-phenone in the presence of phosphoric acid and phosphorous pentoxide at 70° for 20 h (76%) [1089]. 

In 1993 Bedeschi et al.[i2] published the synthesis of the dihydrobenzofurancarboxylic acid 1 using a palladiiun catalysed coupling of trimethylsilylacetylene with methyl 4-(acetylamino)-3-iodo-2-hydroxy-5-chlorobenzoate. Most of the alternatives we investigated were performed prior to this publication and moreover trimethylsilylacetylene is not a reagent of choice to introduce in a production plant due to it s high price and low atom efficiency. 

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