Carboxylic acids by carboxylation with

Carboxylic acids by carboxylation with formic acid, 46, 74 Catalyst, palladium (Lindlar), 46, 89 Chloramine, 46, 18... 

Adamantane, prepared according to Schleyer and supplied by Aldrich Chemical Co., can be converted into the 1 -carboxylic acid by carboxylation with formic acid, (-butanol, and 96% sulfuric acid,2 orfrom 1-bromoadamantane, formic acid, and 96% sulfuric acid.3... 

Carboxylic acids by carboxylation with formic acid, 46, 74... 

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 ... 

Acyl chlorides are readily available They are prepared from carboxylic acids by reaction with thionyl chloride... 

The carboxylic acid produced m the greatest amounts is 1 4 benzenedicarboxylic acid (terephthahc acid) About 5 X 10 Ib/year is produced m the United States as a starting material for the preparation of polyester fibers One important process converts p xylene to terephthahc acid by oxidation with nitric acid... 

Pyridazine aldehydes and ketones with the carbonyl group at the ring or in a side chain react in the usual manner. They form hydrazones, semicarbazides, oximes, etc. Side-chain aldehydes can be easily oxidized to pyridazinecarboxylic acids with silver nitrate and side-chain ketones are oxidized to carboxylic acids by treatment with potassium permanganate or hydrogen peroxide. 

The dianions derived from furan- and thiophene-carboxylic acids by deprotonation with LDA have been reacted with various electrophiles (Scheme 64). The oxygen dianions reacted efficiently with aldehydes and ketones but not so efficiently with alkyl halides or epoxides. The sulfur dianions reacted with allyl bromide, a reaction which failed in the case of the dianions derived from furancarboxylic acids, and are therefore judged to be the softer nucleophiles (81JCS(Pl)1125,80TL505l). 

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). ... 

Acetylisoxazoles are converted to carboxylic acids by boiling with dilute nitric acid. This method allowed the development of a one-stage preparative method for 5-methylisoxazole-3-carboxylic acid (191) starting with acetonylacetone (190). ... 

The a-bromo or a-chloro carboxylic acids 2 are versatile intermediates for further synthetic transformations. For example they can be converted into a-hydroxy carboxylic acids by reaction with water by reaction with cyanide a-cyanocarboxylic acids 7 are obtained, which can be further converted to... 

Acid chlorides are prepared from carboxylic acids by reaction with thionyl chloride (SOCl2), as we saw in the previous section. Similar reaction of a carboxylic acid with phosphorus tribromide (PB ) yields the acid bromide. 

The reaction is a free-radical alkylation in which radicals are derived from a carboxylic acid by decarboxylation with Ag+/S20a-. If has the advantage that the reaction medium can be adjusted so that the monoalkylatcd product precipitates as it is formed, whereby di- or polyalkylation5 is suppressed. 

An OH and a COOH group can be eliminated from P-hydroxy carboxylic acids by refluxing with excess DMF dimethyl acetal. Mono-, di-, tri-, and tetrasubstituted... 

In addition to acyl halides and acid anhydrides, there are a number of milder and more selective acylating agents that can be readily prepared from carboxylic acids. Imidazolides, the (V-acyl derivatives of imidazole, are examples.115 Imidazolides are isolable substances and can be prepared directly from the carboxylic acid by reaction with carbonyldiimidazole. 

Methyl ketones are degraded to the next lower carboxylic acid by reaction with hypochlorite or hypobromite ions. The initial step in these reactions involves base-catalyzed halogenation. The a-haloketones are more reactive than their precursors, and rapid halogenation to the trihalo compound results. Trihalomethyl ketones are susceptible to alkaline cleavage because of the inductive stabilization provided by the halogen atoms. 

Phenacyl esters, easily prepared from carboxylic salts and phenacyl bromide nnder phase transfer catalysis, regenerate the original carboxylic acid by treatment with sodinm hydrogen telluride in DMF. ... 

Wynberg and Feijen studied thieno[3,4-6]thiophene (3) formylation and found that both positions 4 and 6 are attacked. This is in accordance with theoretical predictions. The reaction produces a mixture (7 3) of 4-formyl- (194) and 6-formylthieno[3,4-6]thiophene (195) in 56% total yield after separation and purification. The formyl derivatives obtained were oxidized to the corresponding carboxylic acids 196 and 197, which were converted into 3-ethylpentanoic 198 and 4-methylhexanoic (199) acids by desulfurization with Raney nickel [Scheme 15]. 

The present procedure is based on the method published by Fu, Birnbaum and Greenstein. The yields are increased by the very slow addition of an aqueous solution of sodium nitrite to the reaction mixture as well as by a nwdified work-up procedure, i.e, careful removal of nitrogen oxides and the final decomposition of their adducts with carboxylic acids by buffering with sodium carbonate. 

In the von Pechmann synthesis, originally used to prepare pyran-2-one-5-carboxylic acid (coumalic acid), 2-hydroxybutane-l,4-dioic acid is converted into 3-oxopropanoic acid by treatment with oleum (sulfur trioxide and cone, sulfuric acid), and this product then self-condenses in the acidic medium to give pyran-2-one-5-carboxylic acid (Scheme 4,8a). Pyran-2-one is obtained by decarboxylating coumalic acid by heating it over copper at 650 °C. 

The reaction of a-haloketones (chloro, bromo or iodo) with alkoxide ions to give rearranged esters is called Favorskii rearrangement. For example, 2-chlorocyclohexanone is converted to the methyl ester of cyclopentane carboxylic acid by treatment with sodium methoxide in ether. 

Problem 22.53 A monosaccharide is treated with HCN, the product hydrolyzed and reduced to a carboxylic acid by heating with HI and P. What carboxylic acid is formed if the monosaceharide is (a) o-glucose, (6) D-mannose, (c) D-fructose, (d) o-arabinose, (c) o-erythrose ... 

Cyclobutanecarboxylic acid azides react in a similar manner. The azides were either made from the acid chloride and sodium azide44,45 or directly from the acid by reaction with diphenylphos-phoryl azide.37,46,47 The carboxylic acid azides rearrange via the isocyanates. An example is the reaction of (+ )-ra-2-acetoxycyclobutanecarboxylic acid with diphenylphosphoryl azide to give 4 in quantitative yield.37... 

Niacin is relatively stable to most food-processing operations. It is stable to exposure to air and resistant to autoclaving (and is therefore stable to pasteurization and UHT treatments). The amide linkage of nicotinamide can be hydrolysed to the free carboxylic acid (nicotinic acid) by treament with acid but the vitamin activity is unaffected. Like other water-soluble vitamins, niacin can be lost by leaching. 

Allylic carboxylation. Diethyl oxomalonate (1) undergoes a thermal ene reaction with mono-, di-, and trisubstituted alkenes at 145 180°. The reaction is also subject to catalysis with Lewis acids, which can lead to a different ene product. The products are a-hydroxymalonic esters. The corresponding malonic acids are converted to carboxylic acids by bisdecarboxylation with NaI04 and a trace of pyridine- or with ceric ammonium nitrate (CAN). Diethyl oxomalonate then functions as an cnophilic equivalent of C02. 

Unsubstituted amides can be converted under very mild conditions into the corresponding carboxylic acids by treatment with nitrous acid. This reaction is useful when the usual hydrolysis conditions would affect other functions present, such as hemiacetals,214 as... 

N 14.63% yel cryst powd mp ca 260 with decompn prepd from j6-azoxyben2ene-4-carboxylic acid by treatment with HNO ... 

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