Carboxylic acids oxidative decarboxylations

Anodic Oxidation of Carboxylic Acids Without Decarboxylation... 

Almotriptan has also been synthesized via decarboxylation of the carboxylic acid intermediate 65, but a detailed preparation of 65 was not provided in the patent literature (Scheme 22)." The patent indicates that the carboxy indole 65 was prepared according to the method of Gonzalez.°° Thus, (2-oxo-tetrahydro-3-furanyl)-glyoxylic acid ethyl ester (62) was heated in aqueous H2SO4 to give 2-oxo-5-hydroxypentanoic acid in situ, which was treated with hydrazine 59 to produce hydrazone 63. Fischer cyclization of 63 using HCl gas in DMF gave the lactone 64, which was converted to carboxylic acid 65. Decarboxylation of 65 was catalyzed by cuprous oxide in quinoline at 190 °C to afford almotriptan (5)." ... 

The persulfate ion S2OI-, with or without various transition metal ions, is a particularly effective oxidant, especially for the decarboxylation of carboxylic acids.535 In the presence of silver(I), persulfate oxidation to silver(II) readily occurs and for aliphatic carboxylic acids the decarboxylation mechanism given in Scheme 4 has been established. The aliphatic radicals produced may then disproportionate, abstract hydrogen or be further oxidized to an alcohol. In... 

Several other processes have been developed, however, to accomplish the oxidative decarboxylation of carboxylic acids oxidation by Pb(OAc)4, by iodosobenzene-diacetate, and by Ag(II) salt generated in situ in a catalytic cycle from a variety of peroxides (benzoyl peroxide, percarbonate, perborate) [2] other than the already mentioned peroxydisulfate. Representative examples are shown in Eqs (9)—(12) of Table 2. 

Furan carboxylic acids usually decarboxylate readily, and this method is often used in the laboratory for the preparation of furans. Furan itself can be obtained in good yield from 2-furoic acid in quinoline, with a copper catalyst, while industrial methods employ the catalytic decarbonylation of furfural. Copper powder, copper oxide or copper bronze, or heavy metal oxides,22 are the best catalysts, in combination with quinoline as solvent and weak base.23-28 Dann et al,2fl decarboxylated 2,5-dimethyl-3-furoic acid in 50% yield using barium hydroxide. 3-Furoic acid, which is difficult to obtain in large quantities, is best prepared by controlled decarboxylation of the easily prepared furan tetracarboxylic acid. 

Four methods have been published for the introduction of hydrogen into the 1,2,4-triazine ring, i.e. reduction of halo-1,2,4-triazines, oxidation of hydrazino-l,2,4-triazines, treatment of sul-fonylhydrazino-l,2,4-triazines with base, and decarboxylation of 1,2,4-triazinecarboxylic acids. Decarboxylation of l,2,4-triazine-3-carboxylic acid has been used for the synthesis of the parent 1,2,4-triazine (l) 2 120 this method was also used for the synthesis of other 1,2,4-triazines.270 l,2,4-Benzotriazine-3-carboxylic acid was decarboxylated to give the parent 1,2,4-ben-zotriazine (2).151 271... 

In the case of the reaction of a,P-unsaturated carboxylic acids, oxidation is followed by decarboxylation. Examples are given in Table 9.1. 

This implies that only the 2-methyl group is sufficiently active to undergo oxidation to a carboxylic acid intermediate that then undergoes rapid decarboxylation. 

Synthetic phenol capacity in the United States was reported to be ca 1.6 x 10 t/yr in 1989 (206), almost completely based on the cumene process (see Cumene Phenol). Some synthetic phenol [108-95-2] is made from toluene by a process developed by The Dow Chemical Company (2,299—301). Toluene [108-88-3] is oxidized to benzoic acid in a conventional LPO process. Liquid-phase oxidative decarboxylation with a copper-containing catalyst gives phenol in high yield (2,299—304). The phenoHc hydroxyl group is located ortho to the position previously occupied by the carboxyl group of benzoic acid (2,299,301,305). This provides a means to produce meta-substituted phenols otherwise difficult to make (2,306). VPOs for the oxidative decarboxylation of benzoic acid have also been reported (2,307—309). Although the mechanism appears to be similar to the LPO scheme (309), the VPO reaction is reported not to work for toluic acids (310). 

Alkyl radicals produced by oxidative decarboxylation of carboxylic acids are nucleophilic and attack protonated azoles at the most electron-deficient sites. Thus imidazole and 1-alkylimidazoles are alkylated exclusively at the 2-position (80AHC(27)241). Similarly, thiazoles are attacked in acidic media by methyl and propyl radicals to give 2-substituted derivatives in moderate yields, with smaller amounts of 5-substitution. These reactions have been reviewed (74AHC(i6)123) the mechanism involves an intermediate cr-complex. 

Other interactions of /3-lactams with electrophiles include the oxidative decarboxylation of the azetidin-2-one-4-carboxylic acid (85) on treatment with LTA and pyridine (81M867), and the reaction of the azetidin-2-one-4-sulfinic acid (86) with positive halogen reagents. This affords a mixture of cis- and trans-4-halogeno-/3-lactams (87), the latter undergoing cyclization to give the bicyclic /3-lactam (88) (8UOC3568). 

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... 

Triazole has been prepared by the oxidation of substituted 1,2,4-triazoles, by the treatment of urazole with phosphorus pentasulfide, by heating equimolar quantities of formyl-hydrazine and formamide, by removal of the amino function of 4-amino-l,2,4-triazole, by oxidation of l,2,4-triazole-3(5)-thiol with hydrogen peroxide, by decarboxylation of 1,2,4-triazole-3(5)-carboxylic acid, by heating hydrazine salts with form-amide,by rapidly distilling hydrazine hydrate mixed with two molar equivalents of formamide, i by heating N,N -diformyl-hydrazine with excess ammonia in an autoclave at 200° for 24 hours, and by the reaction of 1,3,5-triazine and hydrazine monohydrochloride. ... 

One-electron oxidation of carboxylate ions generates acyloxy radicals, which undergo decarboxylation. Such electron-transfer reactions can be effected by strong one-electron oxidants, such as Mn(HI), Ag(II), Ce(IV), and Pb(IV) These metal ions are also capable of oxidizing the radical intermediate, so the products are those expected from carbocations. The oxidative decarboxylation by Pb(IV) in the presence of halide salts leads to alkyl halides. For example, oxidation of pentanoic acid with lead tetraacetate in the presence of lithium chloride gives 1-chlorobutane in 71% yield ... 

The decarboxylation reactions of fluonnated carboxylic acids are similar to those of their nonfluonnated counterparts, but predictably many exceptions exist The oxidation of the potassium salts of perfluoro acids with potassium persulfate leads to decarboxylation and coupling [93] (equation 59)... 

The quindoline 224 may be prepared by the condensation of indoxyl-2-carboxylic acid with 6-aminopiperonaldehyde in the presence of hydrochloric acid, when decarboxylation and cyclization take place. Nitric acid oxidation of 224 gave an unstable nitrodicarboxylic acid which decarboxylated readily to a nitromonocarboxylic acid formulated as 8-nitro-8-carboline-3-carboxylic acid (225). ... 

A cursory inspection of key intermediate 8 (see Scheme 1) reveals that it possesses both vicinal and remote stereochemical relationships. To cope with the stereochemical challenge posed by this intermediate and to enhance overall efficiency, a convergent approach featuring the union of optically active intermediates 18 and 19 was adopted. Scheme 5a illustrates the synthesis of intermediate 18. Thus, oxidative cleavage of the trisubstituted olefin of (/ )-citronellic acid benzyl ester (28) with ozone, followed by oxidative workup with Jones reagent, affords a carboxylic acid which can be oxidatively decarboxylated to 29 with lead tetraacetate and copper(n) acetate. Saponification of the benzyl ester in 29 with potassium hydroxide provides an unsaturated carboxylic acid which undergoes smooth conversion to trans iodolactone 30 on treatment with iodine in acetonitrile at -15 °C (89% yield from 29).24 The diastereoselectivity of the thermodynamically controlled iodolacto-nization reaction is approximately 20 1 in favor of the more stable trans iodolactone 30. 

The reaction fails if the decarboxylation produces a radical that is easily oxidized, such as an a-hydroxyalkyl radical.2 In intermediate cases, such as tert-alkyl or a-alkoxyalkyl radicals,2 the yield based on the parent quinono is usually improved by using an excess of persulfate and carboxylic acid to compensate for the loss of radicals due to oxidation (footnote b, Table I). 

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