IV-methylpyrrole

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). 

Competitive metallation experiments with IV-methylpyrrole and thiophene and with IV-methylindole and benzo[6]thiophene indicate that the sulfur-containing heterocycles react more rapidly with H-butyllithium in ether. The comparative reactivity of thiophene and furan with butyllithium depends on the metallation conditions. In hexane, furan reacts more rapidly than thiophene but in ether, in the presence of tetramethylethylenediamine (TMEDA), the order of reactivity is reversed (77JCS(P1)887). Competitive metallation experiments have established that dibenzofuran is more easily lithiated than dibenzothiophene, which in turn is more easily lithiated than A-ethylcarbazole. These compounds lose the proton bound to carbon 4 in dibenzofuran and dibenzothiophene and the equivalent proton (bound to carbon 1) in the carbazole (64JOM(2)304). 

The carbonyl reactivity of pyrrole-, furan-, thiophene- and selenophene-2- and -3-carbaldehydes is very similar to that of benzaldehyde. A quantitative study of the reaction of iV-methylpyrrole-2-carbaldehyde, furan-2-carbaldehyde and thiophene-2-carbaldehyde with hydroxide ions showed that the difference in reactivity between furan- and thiophene-2-carbaldehydes was small but that both of these aldehydes were considerably more reactive... 

While the hydrolytic alkamines, aconine and delphonine, cannot be hydrogenated and have therefore been regarded as saturated, their ultra-violet absorption spectra as bases in solution and in common with those of heteratisine and tetrahydroatisine, show a strong absorption within the range 2,200 to 2,600 A, indicating unsaturation. With the bases in acid solution there is a reduction in intensity and a shift in the position of the absorption. It is assumed that these results arise from association of points of unsaturation with the nitrogen atom, A similar range of absorption is shown by iV-methylpyrrole, as base in solution, but in this case there is no shift in position on acidification. 

The copper-catalyzed decomposition of diazoacetic ester in the presence of pyrrole was first described in 1899 and later investigated in more detail by Nenitzescu and Solomonica. Ethyl pyrrole-2-acetate (13), the normal product of electrophilic substitution, was obtained in 50% yield and was degraded to 2-methylpyrrole. Similarly iV -methylpyrrole with two moles of diazoacetic ester gave, after hydrolysis, the 2,5-diacetic acid (14) while 2,3,5-trimethylpyrrole gave, after degradation, 2,3,4,5-tetramethylpyrrole by substitution of ethoxycarbonylcarbene at the less favored )3-position. Nenitzescu and Solomonica also successfully treated pyrroles with phenyl-... 

IV-Methylpyrrole with (Cp IrH3)2 and 3,3-dimethyl-1-butene gives a couple of unique organometallic products, 86 and 87 (990M134). In 86, the C—H bond in position 2 is activated and a rare tiVC) ti (C=C) coordination mode is realized. Species 87 is a zwitterionic compound containing a triple bond between the iridium atoms. 

Pyrolysis of the methylamine salt (produced by neutralising mucic acid with aqueous methylamine) in the presence of glycerol yields IV-methylpyrrole ... 

Krapcho and Vivelo have described a new formal total synthesis of tropinone (124) and ( )-cocaine (98) (94). Cycloaddition of IV-methylpyrrole (182) and acetylenedicarboxylic acid leads to 183, which is hydrogenated to 184. The diacid mixture 184 is refluxed in MeOH/HCl to yield the diester mixture 185. Addition of this to an excess of metallic sodium in liquid ammonia at — 78°C leads to the N-methylpyrrolidine derivative 186 (cf. 95), whose diethyl analog 147 has earlier been converted to tropinone (124) and (+)-cocaine (98) (78-80) (Scheme 13). 

The reaction of tetrafluorobenzyne with iV-methylpyrrole leads to a good yield of the adduct (106), and with thiophen to tetrafluoro-naphtha-ene 56>. That this latter reaction was the first example of a Diels-Alder reaction of thiophen was shown by following the reaction by XH n.m.r. spectroscopy. Evidence for the intermediacy of the episulphide (107) was obtained. 

New electrophilic substitution reaction methods for the preparation of dipyrromethanes have been reported. The condensation of IV-methylpyrrole with benzaldehyde leading to the corresponding dipyrromethane was promoted by the addition of the organic catalyst, pyrrolidinium tetrafluoroborate <06T12375>. The reaction between pyrrole and N-tosyl imines promoted by metal triflates gave dipyrromethanes whereas tripyrromethane byproducts were not observed <06T10130>. 

Bailey described the first application of the Stille coupling to pyrroles, and one of the earliest examples of any such reaction involving heterocycles [66]. Lithiation of IV-methylpyrrole and quenching with trimethylstannyl chloride gives 2-(trimethylstannyl)pyrrole (76), and palladium-catalyzed coupling with iodobenzene affords l-methyl-2-phenylpyrrole (46) in good yield. 

Methyl cation affinities of benzene and some substituted benzenes have been calculated. These follow a simple additivity rule and the value for benzene shows good agreement with the experimental estimate. Conclusive evidence is presented that these values are linearly related to the corresponding proton affinities. The competition between deuteriation and alkylation in the reaction of radiolytically formed perdeuterio ethyl cations with iV-methylpyrrole and with thiophene has been studied. Deuteriation, the Brpnsted acid pathway, predominates and intramolecular selectivities have been determined for each reaction. ... 

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. 

Different heterocycles, such as furan, 2,3-dihydrofuran, iV-methylpyrrole, thiophene, iV-methylindol or 5-methyl-l,3-triazole, were deprotonated at the a-position with lithium and a catalytic amount of naphthalene or anthracene (1-7%) in THF at room temperature to give, after trapping with methyl iodide, the corresponding methylated products in 56-93%242. 

The benzyne adducts prepared from IV-methylpyrrole (and /V-methylisoindole) are deaminated conveniently by dichlorocarbene generated under phase-transfer conditions (81JOC1025) to give a convenient route to substituted naphthalenes (236) (and anthracenes) (Scheme 51). 

N-, 0-, and S-heterocyclic ligands also form [Os(NH3)5 t)2-(C,C)-L ]2+ complexes [L = 2,6-lutidine, 2,6-lutidinium, pyridinium, N-methylpyridinium, and lV-methyl-4-picolinium (85, 167), NJV -dimethylimidazolium (90), pyrrole (90, 179), IV-methylpyrrole (90, 179), thiophene (90,179), furan (90,179), and 1,3-dimethyluracil (72, 73)]. On oxidation to Os(III), arene ligands are rapidly lost from the coordination sphere, or in the case of the substituted arene ligands with good a donors, rapid linkage isomerization reactions occur (Section V,D). 

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. 

Following the discovery of the unique electronic properties of polypyrrole, numerous polymers of pyrrole have been crafted. A copolymer of pyrrole and pyrrole-3-carboxylic acid is used in a glucose biosensor, and a copolymer of pyrrole and iV-methylpyrrole operates as a redox switching device. Self-doping, low-band gap, and photorefractive pyrrole polymers have been synthesized, and some examples are illustrated [1, 5],... 

Photoreaction of 2-, 3- and 4-iodoquinolines with five-membered heterocycles (pyrrole, iV-methylpyrrole, furan and thiophene) affords the corresponding -(2-heteroaryl)quino-lines (n = 2, 3,4) in appreciable yields526. 3-Halo-1-methylquinolin-2-ones can be converted into 3-aryl-l-methylquinolin-2-ones by photochemical coupling with various aromatic or heteroaromatic compounds527,528. 

A comparison of the relative basicities of pyrrole, furan and thiophene may be made by comparing the pKa values of their 2,5-di-f-butyl derivatives, which were found to be —1.01, -10.01 and -10.16, respectively. In each case protonation was shown by NMR to occur at position 2. The base-strengthening effect of alkyl substitution is clearly apparent by comparison of pyrrole and its alkyl derivatives, e.g. iV-methylpyrrole has a pKa for a-protonation of -2.9 and 2,3,4,5-tetramethylpyrrole has a pKa of +3.7. In general, protonation of a-alkylpyrroles occurs at the a -position whereas /3-alkylpyrroles are protonated at the adjacent a-position. As expected, electron-withdrawing groups are base-weakening thus N-phenylpyrrole is reported to have a pKa of -5.8. The IR spectrum of the hydrochloride of 2-formylpyrrole indicates that protonation occurs mainly at the carbonyl oxygen atom and only to a limited extent at C-5. 

Directive effects on lithiation have also been studied. Regiospecific -metallation of iV-methylpyrrole derivatives and 2-substituted furans can be effected by employing the on o-directing effect of, for example, an oxazolino group 2-lithio-3-bromofuran is the result of treatment of 3-bromofuran with lithium diisopropylamide (LDA) at 80C in THF. 

Several (bis)carbene nickel complexes were tested as catalysts for the dimerisation of propene or 1-butene (Scheme 8.3). IS While the activity of these complexes was very poor in the dimerisation of 1-butene when toluene was used as solvent, turnover frequencies as high as 7,000 mol mol h 1 were observed at ambient temperature with C4Ciim]Cl-AlCL-iV-methylpyrrole (0.45 0.55 0.10) as solvent. With propene as substrate, TOFs of 75,000 mol-moL -lf1 were achieved. Compared to NiCl2(PCy3)2, the activity of the carbene complexes is considerably higher, but selectivity towards the desired, highly branched propene dimer is low. 

As shown in Equation (11), a similar approach was used to prepare IV-methylpyrrole-fused borepin 56 from stannepin 55 <1995CC1249>. 

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