Ring cleavage decarboxylative

Ring cleavage of l-oxo-l,2,3,4-tetrahydro-jS-carboline derivatives (374) may be accomplished by base-catalyzed hydrolysis to yield tryptamine-2-carboxylic acids (375). In the case of the 1,9-dimethyl derivative decarboxylation accompanied acid-catalyzed ring-opening, and the corresponding tryptamine (376) was obtained directly. 

The mechanism for the conversion of the A -oxide (94) to the o-methylaminophenylquinoxaline (96) involves an initial protonation of the A -oxide function. This enhances the electrophilic reactivity of the a-carbon atom which then effects an intramolecular electrophilic substitution at an ortho position of the anilide ring to give the spiro-lactam (98). Hydrolytic ring cleavage of (98) gives the acid (99), which undergoes ready dehydration and decarboxylation to (96), the availability of the cyclic transition state facilitating these processes. ... 

The same metabolite, 11.123, is produced when a carboxy substituent is present at C(3) (i.e., 11.122, R = COOH) [147][148], The mechanism of this activation reaction is also concerted, but, in this case, more extended, with involvement of the carboxylate group and decarboxylation simultaneous with ring cleavage. In vivo in rats, this reaction was clearly slower than for the unsubstituted analogue, with plasma levels of both the prodrug and the metabolite 11.123 being maintained at comparable levels for 24 h. 

The coordination polymerisation of cyclic carbonates with a six-membered ring in the molecule, such as trimethylene carbonate (l,3-dioxan-2-one) and 2,2-dimethyltrimethylene carbonate (5,5-dimethyl-l,3-dioxan-2-one) [148-150], carried out in the presence of metal carboxylates e.g. zinc stearate, tin-based catalysts such as the di(w-butyl)stannic diiodide-triphenylphosphine system [151] or porphinatoaluminium compounds such as (tpp)AlOR [149] is not accompanied with decarboxylation and yields the respective polycarbonates (Table 9.2). The ring cleavage during the polymerisation of trimethylene carbonate and 2,2-dimethyltrimethylene carbonate in the presence of the above catalysts has been found [148,149,151] to occur at the C(0)-0 bond, resulting... 

An unusual reaction occurs when the pyrimido[5,4-c][l,2,5]oxadiazine (152) is allowed to react with a variety of carbon nucleophiles. Nucleophilic attack at a ring nitrogen atom is followed by ring cleavage, and then decarboxylation and recyclization onto the nucleophile residue. The result is a 6,7-disubstituted pteridine (Equation (12)) (153). Appropriate choice of nucleophile may lead to many different types of substituent on the pteridine <86JHC166l, 91H(32)79>. 

The dicarboxylic acid compounds are apt to undergo ring cleavage reactions, particularly in the presence of alkali boiling water converts furazandicarboxylic acid to cyano-oximinoacetic acid, presumably via initial decarboxylation to the monoacid. 

If care is taken to avoid ring cleavage, 5-aryl-l,3,4-oxadiazole-2-carboxylic acids will undergo typical reactions such as the formation of acid chlorides, amides and esters. Decarboxylation may occur on heating, for example with 5-amino-l,3,4-oxadiazole-2-carboxylic acids (77JHC1385), and an amide has been dehydrated to a nitrile (78GEP2808842). 

Derivatives of the 2-phenyl-1,3,4-oxadiazole-5-carboxylic acids give the usual reactions of acids on careful treatment.103 Thus the alcoholysis of the 5-acid chlorides with methanol or ethanol leads to the corresponding ester. Alkaline hydrolysis at 30° produces the carboxylic acid which on warming is decarboxylated to 2-phenyl-1,3,4-oxadiazole. Even a slight increase in the severity of the reaction conditions produces ring cleavage.103 The alkaline hydrolysis of 2-phenyl-5-(p-cyanophenyl)-1,3,4-oxadiazole with addition of H202 leads to 2-phenyl-5-(p-carboxamidophenyl)-1,3,4-oxadiazole.23... 

Although benzoate is generally metabolized by oxidative decarboxylation to catechol followed by ring cleavage, nonoxidative decarboxylation may also occur (1) strains of Bacillus megaterium transform vanillate to guaiacol by decarboxylation (Crawford and Olson 1978) and (2) a number of decarboxylations of aromatic carboxylic acids by facultatively anaerobic Enterobacteri-aceae have been noted in Chapter 4, Section 4.3.2. 

In aqueous solution indoxazene-3-carboxylic acid undergoes slow but quantitative decarboxylation and ring cleavage to o-cyanophenol (t1/2 at 30°C, 7 days).53 From a careful study of substituent and solvent effects on the rate of decarboxylation, and on tritium labeling studies, it is concluded that the reaction involves an intermediateless, concerted loss of carbon dioxide via a transition state conveniently represented as 38, rather than by a stepwise process through carbanion 39 (Scheme 3).8,53... 

Decarboxylation and ring cleavage, followed by cycloaddition of the nitrile oxide 118, probably account for the formation of adducts (119) from 4-methylfuroxan-3-carboxylic acid (117).361 Analogously, 4-phenylfuroxan forms an adduct (or adducts) with mesityl oxide, apparently derived via the nitrile oxide 120, which is produced from the furoxan under a variety of extremely mildly basic conditions.362... 

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