Pyrrole-2,4-dicarboxylic acid, 5-methyl

To 5a] In view of the behaviour of esters of pyrrole-dicarboxylic acids, already reported, it is interesting to notice that methyl pyrrole-2-carboxy-late undergoes alkaline hydrolysis considerably faster than the 3-isomer [10 A 2 (1. mole i sec ) (25°), 231, 4 1 and 0 59, for ethyl pyrrole-1-, and methyl pyrrole-2- and -3-carboxylate, respectively, in 56 per cent aqueous acetone]. The effect is attributed to intramolecular hydrogen bonding in the transition state (109)374 (cf. to c above). 

Pyrrole-2,3-dialdehyde, 1-methyl-pyrrolopyridazine synthesis from, 4, 517 Pyrrole-2,5-dicarboxylic acid, 3,4-dihydroxy-l-phenyl-diethyl ester... 

Pyrrole-3,5-dicarboxylic acid, 2-dichloromethyl-4-methyl-diethyl ester... 

Pyrrole- and indole-carboxylic acid chlorides react with dialkyl- and diaryl-cadmium to yield the ketones and it is noteworthy that the reaction of the anhydride of indole-2,3-dicarboxylic acid with diphenylcadmium produces 3-benzoylindole-2-carboxylic acid and not its isomer (53JCS1889). The ability of l-methylindole-2-carboxylic acid to react with nucleophiles is enhanced by conversion into the mixed anhydride with methanesulfonic acid. The mixed anhydride reacts with carbanions derived from diethyl malonate and from methyl acetate to yield the indolyl (3- keto esters (80TL1957). 

TABLE 1.78 2-ACYL-I-METHYL-5-SUBSTITUTED PYRROLE-3,4-DICARBOXYLIC ACID DIMETHYL ESTERS FROM 2,5-DISUBSTITUTED OXAZOLES, METHYLTRIFLATE, AND DMAD, 243... 

Methyl-4-nitro-1,3-benzenediol, M-70097 l/7-Pyrrole-3,4-dicarboxylic acid Me ester, in P-70183 C7H7NO4S... 

Only the trifluoromethyl group has been subjected to reduction in this class of compound. Although not reduced by zinc in acetic acid or by sodium in ethanol, diethyl 2-methyl-4-(tri-fluoromethyl)-1//-pyrrole-3,5-dicarboxylate (1) is reduced at the trifluoromethyl group with an excess of lithium aluminum hydride to give the corresponding tetramethyl derivative 2 sodium borohydridc in ethanol is quite inefficient.104... 

The nitrovinyl system has been found to be a better diene than the corresponding vinyl analogs. Condensation of l-methyl-2-(2-nitrovi-nyl)pyrrole 117 with maleic acid yielded ALmethylindole-4,5-dicarboxylic anhydride 118. Failure to isolate the expected diacid 183 is probably due to cyclization to the anhydride in the acidic medium created by the elimination of nitrous acid during the condensation. This process is believed to follow the normal Diels-Alder [4-I-2]-cycloaddition pathway with subsequent loss of nitrous acid [73JCS(P1)2450]. 

Diels-Alder addition product, from 1-methylpyrrole and maleic anhydride 2 is a further example of this sort of reaction. 2-Methylpyrrole behaves similarly, but the initial product (10) from pyrrole is obtained in small yield because it reacts further (p. 88). Pyrroles such as 2-methyl-, 1,2-dimethyl-and 2,4-dimethyl-pyrrole undergo similar Michael additions with methyl acetylenedicarboxylate s, 254 jn the third instance two molecules of the pyrrole reacting to form (11). 1-Methoxycarbonylpyrrole reacts at the 2-position with acetylene dicarboxylic acid254 as well as giving a Diels-Alder type of product (p. 82). With the same acid, ethyl 3,5-dimethylpyrrole-2-carboxylate undergoes Michael addition at the vacant jS-position giving (12). Other examples of reactions with dienophiles are discussed below... 

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