Carboxylates, "/-bromo

Cleavage Gem-dihalides and monohalides have been dehalogenated to chiral monohalides in the presence of alkaloids [397, 398]. l,l-Diphenyl-2-bromo-2-carboxyl (bromo or methyl carboxylate) cyclopropanes are cathodically debromi-nated in the presence of alkaloid cations with enantioselectivities up to 45% ee. A mechanism is proposed whereby the alkaloid is adsorbed at the Hg cathode, which protonates face selectively the carbanion generated by 2e reduction from the bromide [399]. 

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 ... 

Another useful route to cyciopentanes is the ring contraction of 2-bromo-cydohexanones by a Favorskii rearrangement to give csrdopcntanecarboxylic acids. If a 0 dibromoketones are used, ring opening of the intermediate cydopropanone leads selectively to, y-unsaturated carboxylic acids (S.A, Achmad, 1963, 1965 J. Wolinsky, 1965). 

There are also palladium-catalysed procedures for allylation. Ethyl 3-bromo-l-(4-methylphenylsulfonyl)indole-2-carboxylate is allylated at C3 upon reaction with allyl acetate and hexabutylditin[27], Ihe reaction presumably Involves a ir-allyl-Pd intermediate formed from the allyl acetate, oxidative addition, transmetallation and cross coupling. 

A standard method for the preparation of an a ammo acid uses a bromo carboxylic acids as the substrate and aqueous ammonia as the nucleophile... 

Substitutions that displace electrons toward the carboxyl group of aromatic acids diminish the rate of the reaction (16). The substitution of fluoromethoxy or ethoxy groups in the ortho position has an accelerating action, whereas iodo, bromo, nitro, or methyl groups produce retardation. The influence of groups in the meta and para positions is not nearly so marked (17). 

Primary synthesis has limited application in making pyrimidine-carboxylic acids or even their esters. However, some pyrimidine-4(and 5)-carboxylic acids can be effectively so made. For example, bromomucic acid (785) reacts as an aidehydo ketone with S-methyl-thiourea to give 5-bromo-2-methylthiopyrimidine-4-carboxylic acid (786) directly (53JCS3129) while the Whitehead synthesis (Section 2.13.3.1.2<7) can give, for instance, 3-methylcytosine-5-carboxylic acid (787) (55MI21300). 

The base-promoted ring contraction of 3-bromo-2-pyrones to 2-furoic acids cf. Scheme llOd) is a well exemplified reaction 01CB1992,69JCS(C)1950,73JCS(P1)1130> which has also been applied to the obtention of benzofuran-2-carboxylic acids frorn 3-bromocoumarins 08CB830,70KGS(S2)166), Similar base treatment of 3-amino-2-pyrones provides pyrrole-2-carboxylic acids (Scheme IlOe) 75JHC129). 

Grignard reagents can be successfully prepared from 4-iodoisoxazoles and these react with CO2 and ketones to give carboxylic acids and methanols, respectively. 3-Bromo- or... 

Furan-2-carboxylic acid, 5-bromo-, methyl ester UV, 4, 588 <57JOC323>... 

Azetidine, 7V-bromo-, 7, 240 Azetidine, AT-r-butyl- N NMR, 7, 11 Azetidine, AT-t-butyl-3-chloro-transannular nucleophilic attack, 7, 25 Azetidine, 3-chloro-isomerization, 7, 42 Azetidine, AT-chloro-, 7, 240 dehydrohalogenation, 7, 275 Azetidine, 7V-chloro-2-methyl-inversion, 7, 7 Azetidine, 3-halo-synthesis, 7, 246 Azetidine, AT-halo-synthesis, 7, 246 Azetidine, AT-hydroxy-synthesis, 7, 271 Azetidine, 2-imino-stability, 7, 256 Azetidine, 2-methoxy-synthesis, 7, 246 Azetidine, 2-methyl-circular dichroism, 7, 239 optical rotatory dispersion, 7, 239 Azetidine, AT-nitroso-deoxygenation, 7, 241 oxidation, 7, 240 synthesis, 7, 246 Azetidine, thioacyl-ring expansion, 7, 241 Azetidine-4-carboxylic acid, 2-oxo-oxidative decarboxylation, 7, 251 Azetidine-2-carboxylic acids absolute configuration, 7, 239 azetidin-2-ones from, 7, 263 synthesis, 7, 246... 

Benzo[b]thiophene-2-carboxylic acid, 3-bromo-synthesis, 4, 890... 

Furan-2-carbonyl chloride, 5-alkyl-3,4-dichloro-synthesis, 4, 690 Furancarboxamides rotational isomerism, 4, 543 Furan-2-carboxylic acid, 5-acetylamino-ethyl ester reactions, 4, 647 Furan-2-carboxylic acid, amino-properties, 4, 708 Furan-2-carboxylic acid, 5-bromo-nitration, 4, 603, 711 Furan-2-carboxylic acid, 3-methyl-methyl ester bromination, 4, 604 Furan-2-carboxylic acid, 5-methyl-nitration, 4, 602... 

Indole-2-carboxylic acid, 5-bromo-l-hydroxy-tautomerism, 4, 197-198 Indolecarboxylic acid chloride synthesis, 4, 288... 

Claisen condensation, 6, 156 reactions, S, 92 IsothiazoIe-3-carboxyIic acids decarboxylation, 6, 156 Isothiazole-4-carboxylic acids decarboxylation, 6, 156 Isothiazole-5-carboxylic acids decarboxylation, S, 92 6, 156 IR spectroscopy, 6, 142 Isothiazole-3-diazonium borofluoride decomposition, 6, 158 IsothiazoIe-4-diazonium chloride, 3-methyl-reactions with thiourea, 6, 158 Isothiazole-5-diazonium chloride, 4-bromo-3-methyl-halogen exchange, 6, 163 Isothiazole-5-diazonium chloride, 3-methyl-reactions... 

Pyrimidine-4-carboxylic acid, 5-bromo-2-methyl-synthesis, 3, 126... 

Pyrrole-3-carboxylic acid, l-benzoyl-5-bromo-2,4-dimethyl-ethyl ester chlorination, 4, 271... 

Thiophene-4-carboxylic acid, 3-bromo-debromination, 4, 78 Thiophenecarboxylic acids acidity, 4, 71... 

The methyl ester (100, R = CH3), derived from this A-nor acid by treatment with diazomethane, is different from the ester (102) obtained either by Favorskii rearrangement of 2a-bromo-5a-cholestan-3-one (101) or by the action of cyanogen azide on 3-methoxy-5a-cholest-2-ene (103) followed by hydrolysis on alumina. The ketene intermediate involved in photolysis of (99) is expected to be hydrated from the less hindered a-side of the molecule to give the 2j -carboxylic acid. The reactions which afford (102) would be expected to afford the 2a-epimer. These configurational assignments are confirmed by deuteriochloroform-benzene solvent shifts in the NMR spectra of esters (100) and (102). ... 

Finally, certain 3-substituted compounds can be prepared by utilizing the - meta) directing powet (cf. Section IV,B) of some groups in the 2-position which afterward can be removed. 3-Nitrothiophene is prepared by nitration of 2-thiophenesulfonyl chloride and by removal of the sulfonic acid group of the 4-nitro-2-sulfonyl chloride formed with superheated steam. Another approach to 3-nitrothio-phene is to nitrate 2-cyanothiophene, separate the 4-nitro-2-cyano-thiophene from the 5-isomer, hydrolyze, and decarboxylate. A final method of preparation of 3-nitrothiophene is by simultaneous de-bromination and decarboxylation of 5-bromo-4-nitro-2-thiophene-carboxylic acid obtained through the nitration of methyl 5-bromo-2-thiophenecarboxylate. 

Carboxyl groups are easily removed during nitration especially at higher temperatures. A detailed study on the nitration of 5-bromo-2-thiophenecarboxylic acid showed that the proportion of 2,4-dinitro-5-bromothiophene increased with the concentration of sulfuric and nitric acid. The mechanism of this decarboxylative nitration... 

Isothiazole-3-carboxylic acid and its 4-bromo derivative have been obtained by oxidation of the corresponding aldehydes with silver oxide. They form acid chlorides, esters, and amides. The amides may be dehydrated to give the corresponding nitriles. ... 

Reaction of 2 equiv of 2-aminopyridines with 2-hydropolyfluoroalk-2-anoates 351 in MeCN in the presence of NEts at 90 °C for 50 h afforded a mixture of the isomeric 2-oxo-2H- and 4-oxo-4//-pyrido[l,2-n]pyrimidines 110 and 111. Reaction of 3 equiv of 2-amino-pyridines and 2-hydropoly-fluoroalk-2-enoates 351 in MeCN in the presence K2CO3 could be accelerated by ultrasonic irradiation (125W). 2-Amino-6-methylpyridine yielded only 2-substituted 6-methyl-4//-pyrido[l,2-n]pyrimidin-4-ones 111 (R = 6-Me), whereas 2-amino-5-bromopyridine gave a mixture of 7-bromo-4//-pyrido[l,2-n]pyrimidin-4-one (111, R = 7-Br, R = CF2C1) and 2-(chlor-o,difluoromethyl)-6-bromoimidazo[l, 2-n]pyrimidine-3-carboxylate in 44 and 8% yields, respectively (97JCS(P 1)981). Reactions in the presence of K2CO3 in MeCN at 90°C for 60h afforded only imidazo[l,2-n]pyrimidine-3-carboxylates. 

Cyclocondensation of 2-chloronicotinic acid with 2-amino-5-iodobenzoic acid and methyl 2-amino-4-bromobenzoate in boiling EtOH in the presence of cone. HCl for 18 h gave the 2-iodo and 3-bromo derivatives of 11-0X0-1 l/f-pyrido[2,l-6]quinazoline-6-carboxylic acid (98MIP1, 98MIP2, 99USP5908840, 99USP5914327). 

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