Methyl m-chlorobenzoate

Methyl esters may be prepared by reaction of the aromatic carboxylic acid with diazomethane (cf. Section 4.2.25, p. 433) or, more conveniently, by reaction with a boron trifluoride-methanol reagent. The latter procedure is illustrated by the preparation of methyl m-chlorobenzoate and dimethyl terephthalate (Expt 6.164). t-Butyl esters may be prepared by conversion of the acid into an N-acylimidazole by reaction with N,N -carbonyldiimidazole, followed by reaction with t-butyl alcohol in the presence of DBU62 (Expt 6.165). 

Place 9.4 g (0.06 mol) of m-chlorobenzoic acid and 66 ml (0.12 mol) of boron trifluoride-methanol complex (14% w/v of BF3 Section 4.2.8, p. 421) in a 250-ml round-bottomed flask. Heat the mixture under reflux on an oil bath for 2 hours, cool and pour into about 250 ml of saturated sodium hydrogen carbonate solution. Extract the organic product with three 50 ml portions of ether, dry the ethereal extract over magnesium sulphate and evaporate on a rotary evaporator. Distil the residue under reduced pressure and collect the methyl m-chlorobenzoate as a colourless liquid of b.p. 63 °C/3mmHg the yield is 9.3 g (91%). 

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). 

The following couples were tested p-chlorobenzonitrile/p-chloro-acetophenone, p-chloroacetophenone/p-chlorodiphenyl, p-chlorodiphenyl /chlorobenzene, p-chlorodiphenyl/p-chlorofluorobenzene, chlorobenzene /p-chlorotoluene, chlorobenzene/p-chloroanisole, p-chloroacetophenone/ methyl ester of m-chlorobenzoic acid, chlorobenzene/m-chlorotoluene, p-chlorodiphenylether/p-chlorotoluene, m-chlorodiphenylether/chloroben-zene, m-chlorodiphenylether/p-chlorotoluene, chlorobenzene/methyl ester of m-chlorobenzoic acid, chlorobenzene/p-bromoanisole, p-bromoaceto-phenone / p-chlorobenzonitrile, p-bromobenzonitrile / p-chloroacetophe-none, bromobenzene/p-chlorodiphenyl, m-bromotoluene/chlorobenzene, and p-chlorodiphenyl/p-bromotoluene. 

Benzoic acid, 3-chlora-, methyl ester Benzoic acid, m-chloro-, methyl ester m-Chlorobenzoic acid methyl ester EINECS 220-814-1 HSDB 5465 Methyl 3-chlorobenzoate. 

Additional examples of this fascinating chemistry are listed in Table 1 [9, 10]. For Entries 1-3, the initially formed m-chlorobenzoate product is methanolized to the methyl ether (not shown). Entry 3 represents an attractive synthesis of pyrrolo[3,2-d]pyrimidines [11]. Water is the nucleophile in Entry 4, not m-chlorobenzoate, in a sequence that provides pyrrolo[3,2-c]coumarins [12]. Entry 5 describes the preparation of pyrrolo[3,2-c] [1] benzothi-opyran-4-ones, which is a new ring system and where water has captured the intermediate 3-methylene-2-hydroxy indoline [13]. Entry 6 features the synthesis of pyrrolo[3,2-c]pyrones [14]. Entry 7 describes a similar rearrangement of A-alkyl-A-allenylmethylanihnes with magnesium monoperoxyphthalate (MMPP) to afford 2-vinylindoles [15], This reaction presumably follows the one described earlier, although none of the presumed intermediates could be isolated. 

Hindered substrates, such as 2-chloro-m-xylene, can also be coupled efficiently, although the utihty of this Kumada cross-couphng process is Hmited by its relatively low functional-group tolerance. Thus, for example the reaction of methyl 4-chlorobenzoate results in the formation of significant amounts of undesired side products. 

Preparation 3-4 A 12 / flask was equipped with a mechanical stirrer, thermometer, N2 inlet, drying tube outlet, and addition funnels. Tetrahy-drofuran and p-xylene were charged to the flask. The catalyst tetrabutyl ammonium m-chlorobenzoate, as solution in acetonitrile, was then added. Then the initiator, l-methoxy-l-trimethylsiloxy-2-methyl propene was injected. 2-Dimethylaminoethyl methacrylate was added during 45 min. Then, butyl methacrylate, was added during 30 min. Some time afterwards dry methanol was added to the solution and distillation started to remove the solvent. After completion of the distillation, isopropanol was added. 

A mixture of m-chloroperbenzoic acid (MCPBA, 55% purity in 10% m-chlorobenzoic acid and 35% water, from Merck, 0.32 g), methyl oleate (Aldrich, 0.2 g, 0.68 mmol) and deionized water (25 mL) was placed in a water-cooled glass cell. Sonication was carried out using a 20-kHz (53W cm"2) ultrasound horn (Sonoreactor, Undatim Ultrasonics, Louvain la Neuve, Belgium), in a water-cooled jacketed glass cell (40 mm i.d., 80 mm length). The tip of the ultrasonic probe was submersed to 5 mm below the surface of the reaction mixture and the system was sonicated for 15 min with the temperature maintained at about 20°C by water circulating through the jacket. 

A soln. of m-chloroperoxybenzoic acid in chloroform added to an ice-cooled soln. of 6-methyl-6-hepten-2-one in the same solvent, allowed to stand overnight in a refrigerator, and the resulting crude epoxy ketone containing a small amount of m-chlorobenzoic acid distilled in vacuo ( )-frontalin. Y 58.5%. K. Mori, S. Kobayashi, and M. Matsui, Agri. Biol. Chem. (Tokyo) 39, 1889 (1975) review of 6,8-dioxabicyclo[3.2.1]octanes s. B. P. Mundy, K. B. Lipkowitz, and G. W. Dirks, Heterocycles 6, 51 (1977). 

Preparation by Fries rearrangement of 4-chloro-2-methyl-phenyl m-chlorobenzoate with aluminium Cl chloride at 180° for 10 min [1074],... 

Chlorobenzoic acid [535-80-8] M 156.6, m 154-156°, 158°, dj 1.496, pK 3.82 (5.25 in 50% dimethylacetamide). Crystd successively from glacial acetic acid, aqueous EtOH and pet ether (b 60-80°). It also recrysts from CgH6 or Et20-hexane, and sublimes at 55° in a vacuum. [Anal Chem 26 726 1954] The methyl ester has m 21°, b 231°/atm. The S-benzyl thiouronium salt has m 164-165° (from EtOH) [Acta Chem Scand 9 1425 1955 J Chem Soc 1318 I960],... 

Benzoic m-Toluic (Benzoic acid, 3-methyl-] p-Toluic [Benzoic acid, 4-methyl-J 3,5-Dimcthylbcnzoic [Benzoic acid, 3,5-dimcthyl-] p-Chlorobenzoic [Benzoic acid, 4-chloro-] p-Bromobenzoic [Benzoic acid, 4-bromo-J Phthalic [ 1,2-Bcnzcncdicarboxylic acid] Toluene [Benzene, methyl-] (78) m-Xylene [Benzene, 1,3-dimethyl-] (82) />-Xylene [Benzene, 1,4-dimethyl-] (74) Mesitylene [Benzene, 1,3,5-trimethyl-] (82) p-Chlorotolueno [Benzene, l-ehloro-4-methyl-] (94) p-Bromotolucnc [Benzene, l-bromo-4-methyl-] (94) o-Xylene [Benzene, 1,2-dimethyl-] (64)... 

Flak and Schaber (5,62) used reverse-phase HPLC for the quantitative and simultaneous determination of benzoic acid and sorbic acid, as well as 4-hydroxybenzoic acid, salicylic, 5-nitrofurylacrylic, and p-chlorobenzoic acid and the EsHBA (methyl, ethyl, propyl) in wines and beverages. The first five compounds can be determined by isocratic elution from a Clg column using 0.12 M acetate, pH 3.8 acetonitrile (85 15), and all may be separated with gradient elution (increasing acetonitrile from 10 to 60%, with a simultaneous decrease of the pH of the acetate buffer from 3.9 initially to 3.3). 

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