Methylpyrrole formation

The first proton to be removed from iV-methylpyrrole by w-butyllithium is from an a-position a second deprotonation occurs to give a mixture of 2,4- and 2,5-dilithiated derivatives. The formation of a 2,4-dilithio derivative is noteworthy since in the case of both furan and thiophene initial abstraction of a proton at C-2 is followed by proton abstraction from C-5 (77JCS(P1)887). iV-Methylindole, benzo[6]furan and benzo[6]thiophene are also deprotonated at C-2. Selenophene and benzo[6]selenophene and tellurophene and benzo[6]tellurophene similarly yield 2-lithio derivatives (77AHC(21)119). 

Directive effects on lithiation have also been studied. The regiospecific /3-metallation of A-methylpyrrole derivatives and 2-substituted furans has been effected by employing the directive effect of the oxazolino group (82JCs(Pl)1343). 2-Substituted furans and thiophenes are metallated in the 5-position. The formation of 2-lithio-3-bromofuran on treatment of... 

The reactions of pyrroles with dimethyl acetylenedicarboxylate (DMAD) have been extensively investigated. In the presence of a proton donor the Michael adducts (125) and (126) are formed. However, under aprotic conditions the reversible formation of the 1 1 Diels-Alder adduct (127) is an important reaction. In the case of the adduct from 1-methylpyrrole, reaction with a further molecule of DMAD can occur to give a dihydroindole (Scheme 48) (82H(19)1915). 

In contrast, when the irradiation is performed on 2-cyanopyrrole, the isomeric products are observed. In fact, in this case, the corresponding Dewar pyrrole shows a lower energy than in the previous case, allowing the formation of the isomeric products (Fig. 6). When 2-methylpyrrole is used as substrate, the formation of the triplet state is favored, but this triplet state cannot evolve through the formation of the biradical intermediate. 

Cold, aqueous sodium hydroxide brings about the collapse of diethyl 2,7-dimelhyl-4//-azepine-3,6-dicarboxylate (3) to the 1-substituted pyrrole 4,29 whereas with aqueous ethanolic ammonia solution ring contraction is accompanied by loss of the butenoic acid side chain and formation of ethyl 2-methylpyrrole-3-carboxylate (94% mp 77-78cC). 

The presence of a 2-substitutent in 3-phenylazirines (17, R —H in Scheme 21) modifies the mode of reaction with molybdenum carbonyl.47 In contrast to pyrazine formation for (17, R =H see Section V,C,2), the alkenyl azirine (18, Scheme 22) is transformed in excellent yield into 2-phenyl-5-carboxy-methylpyrrole. This product probably arises by intramolecular cyclization within an intermediate dienylnitrene intermediate, and related reactions have been devised to synthesize isoxazoles (see Section IV,E,2) and pyrazoles (see Section IV,D,1).47 The molybdenum carbonyl-promoted formation of 2,5-disubstituted pyrroles47 has analogy in uncatalyzed thermal, but not photochemical decomposition of 3-phenyl-2//-azirine 2-acrylate.49... 

The formation of a small amount of naphthalene as a by-product of the reaction of benzyne with iV -methylpyrrole was noted by Wittig and Behnisch. Some related examples have recently been described. The tetrachloronaphthalen-l,4-imine (108) with benz5me gave N-methylcarbazole, which it is tempting to see as arising from the reaction of an intermediate zwitterion (compare 166) with another molecule of benzyne or, more likely, a benzyne precursor. The complementary product, 1,2,3,4-tetrachloronaphthalene, was not identified in this case. 

A -methylpyrrole. It was assumed that pyrolysis occurred at the inlet temperature and that ficine and isoficine consisted of chrysin substituted with M-methylpyr-role at positions 8 and 6, respectively. The presence of chrysin as part of the molecule was confirmed by its formation from 4 by alkaline hydrolysis. 

The positions of the 13C resonances for pyrrole and IV-methylpyrrole are solvent dependent (Table 13). Similar effects may be discerned in the two molecules, suggesting the formation of similar solvent association complexes. Solvent shifts of 13C resonances in pyrroles do not always parallel those of corresponding H resonances, an effect which does not appear to have been adequately explained and which merits further investigation. 

The polymeric pyrrolic autoxidation products probably result from the oxidized monomeric systems, which are analogous in structure to those isolated from photooxidation and peroxide oxidation reactions. Thus, for example, analysis of the products of the autoxidation of 1-methylpyrrole (Scheme 47) would suggest that 1 -methyl-A3-pyrrolin-2-one (153) is initially formed from a radical reaction of the pyrrole with triplet oxygen. This reaction sequence should be compared with that proposed for the oxidation of pyrroles with hydrogen peroxide (Scheme 50), which yields (181), (182) and (183) as the major isolable products. The acid-catalyzed reaction of a pyrrole with its oxidation product e.g. 153) also results in the formation of polymeric material and the formation of pyrrole black is probably a combination of oxidation and acid-catalyzed polymerization processes. 

The oxidation of indoles and pyrroles by Fe(III) ions is less predictable than other chemical oxidations. 2-Methyl- and 3-methyl-indoles, respectively, yield (187) and (188), and whilst pyrroles may form pyrrole black , the rate of oxidation of pyrrole and of 1-methylpyrrole appears to be relatively slow. C-Alkyl and electron-donating substituents enhance the formation of oligimers, e.g. (189) -> (190) and (191) -> (192), and although electron-withdrawing substituents reduce the susceptibility of the pyrrole ring to oxidation, acyl- and alkoxycarbonyl-pyrroles of the type (193) are readily oxidized to the thermochromic dimer (194), which is in equilibrium with the dimer (195) via the monomeric pyrrolyl radical (72BCJ3584). 

Pyrrole and 1-alkylpyrroles generally react with ir-deficient alkenes and alkynes to give Michael addition products (see Section 3.05.1.2.6), but Diels and Alder (3lLA(490)267) reported that 1-methylpyrrole also gave a 1 2 adduct with DM AD formulated as (229), which could be derived from a [w4+w2] cycloaddition of a second molecule of DM AD with the initially formed Michael adduct (cf. Section 3.05.2.3). Subsequent work, however, has shown structure (229) for the 1 2 adduct to be incorrect, the true structure being (230) (63AHC(i)i25, 78AHC(23)265). The formation of the dihydroindole (230) requires the initial... 

The formation of 3-pyrrolylcarbinols (280) from the photochemically induced reaction of pyrrole, or its 1-alkyl derivatives, with aliphatic aldehydes and ketones is thought to proceed via an oxetane intermediate (279) (79JOC2949). In contrast, the analogous reaction of 1 -phenylpyrrole with benzophenone leads to the formation of the diphenyl(2-pyrrolyl)car-binol, whilst the oxetane (281) has been isolated from the photoaddition of 1-benzoylpyrrole and benzophenone (76JHC1037, B-77MI30500). 2-Benzoyl-1-methylpyrrole undergoes a normal Paterno-Buchi photocyclization with 2,3-dimethylbut-2-ene, via the n -> v triplet... 

Decomposition of l-methyl-2-pyrrolidinone (67) was studied by vapor-phase photolysis (72JA8281). Irradiation (Hg sensitized) led, in addition to extensive polymer formation, to the following products carbon monoxide (31%), ethene (24%), water (24%), l,3,5-trimethyl-hexahydro-l,3,5-triazine (8%), 1-methylazetidine (6%), 1-methylpyrrole, and methane (<1%). The mechanism of formation of most of these products involves... 

The base peak of N-benzylpyrrole is attributable to the tropylium ion (56, mje 91) resulting from cleavage corresponding to that of route (a) for methylpyrrole (Scheme 2). The alternative cleavage involving the formation of the immonium ion and a phenyl radical occurs to a much lesser extent (9.7%). 

The reactions of t with pyrrole and 1-methylpyrrole have been investigated by Kubota and Sakurai (117,135). The formation of adducts 71 and 72 upon irradiation of t-1 in pyrrole solvent is proposed to occur via a nonfluorescent singlet ex-ciplex, which undergoes N-H atom transfer from pyrrole to t-1 to yield a radical pair (117). Radical pair combination occurs at C-2 or C-3 of the pyrrole radical to yield adducts 71 and 72, which isomerize to yield the isolated products, 73 and 74... 

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