Pyrroles, alkylation hydrogenation

The dipole moment varies according to the solvent it is ca 5.14 x 10 ° Cm (ca 1.55 D) when pure and ca 6.0 x 10 ° Cm (ca 1.8 D) in a nonpolar solvent, such as benzene or cyclohexane (14,15). In solvents to which it can hydrogen bond, the dipole moment may be much higher. The dipole is directed toward the ring from a positive nitrogen atom, whereas the saturated nonaromatic analogue pyrroHdine [123-75-1] has a dipole moment of 5.24 X 10 ° C-m (1.57 D) and is oppositely directed. Pyrrole and its alkyl derivatives are TT-electron rich and form colored charge-transfer complexes with acceptor molecules, eg, iodine and tetracyanoethylene (16). 

Alternatively, Ballini devised a new strategy to synthesize tri-alkylated pyrroles from 2,5-dialkylfurans and nitroalkanes <00SL391>. This method involves initial oxidation of 2,5-dimethylfuran with magnesium monoperoxyphthalate to cA-3-hexen-2,5-dione (6). Conjugate addition of the nitronate anion derived from the nitro compound 7 to 6 followed by chemoselective hydrogenation of the C-C double bond of the resulting enones 8 (obtained by elimination of nitrous acid from the Michael adduct) completes the conversion to the alkylated y-diketones 9. Final cyclization to pyrroles 10 featured improved Paal-Knorr reaction conditions involving reaction of the diketones with primary amines in a bed of basic alumina in the absence of solvent. 

Many synthetic methods have been reported for the pyrrolidine alkaloids, including procedures based on the Hofmann-Loffler reaction 132,412), the metal hydride reduction of pyrrolines 413,414), the a-alkylation of N-nitro-sopyrrolidine 412,415), the catalytic hydrogenation of pyrroles 133), the reductive amination of 1,4-diketones 25,138), the direct alkylation of 1-methoxy-carbonyl-3-pyrroline 416), the versatile synthesis from the Lukes-Sorm dilac-... 

Catalytic hydrogenation of 2-alkyl-2,5-dihydro-l//-pyrrole with 5% rhodium on carbon gave 2-substituted pyrrolidines in 95-96% ee (Pirkle analysis42) without attendant racemization. 

To a 0.02 M soln of 2-alkyl-2,5-dihydro-l //-pyrrole (85-90% pure) in methanol is added with stirring 5% rhodium on carbon (catalyst/substrate 1 20). The mixture is pressurized (4.6 x 107 Torr) with hydrogen and is stirred at 25 °C for a minimum of 5 h. The catalyst is removed by vacuum filtration, the solution is concentrated under reduced pressure and the residue is purified by bulb-to-bulb distillation to give the product in 95% purity. 

Wang et al.122 have described methylation and alkylation of pyrrole and obtained mono-N-alkylation products with yields of 30-85%. An increase in the ratio of N- versus C-alkylation of pyrrole (and of other heterocyclic compounds bearing an acidic hydrogen atom) has been observed by Guida and Mathre,124 who carried out the reaction with t-BuOK, 18-crown-6 (10%), and diethyl ether. 

Catalytic reduction of the C-alkenyl and -alkynyl substituents over palladium or Raney nickel can be effected without concomitant hydrogenation of the heterocyclic system to give the corresponding alkyl-pyrroles and -indoles (72HC(25-2)65, B-77MI30504). 

CulI(HCor) show similar absorption spectra to those of the A-alkyl analogue, and the extra hydrogen atom is probably attached on the pyrrolic nitrogen.239 The X-ray structure of Cu(N21-MeCor) indicates the N-21 atom to be in an sp3 configuration and the pyrrole ring twisted out of the mean plane by 23°,240... 

Two alkyl radicals at position 4 make impossible pyrrolization of the dihydropyrroles 94, while with a hydrogen atom present in this position, the conversion to the corresponding pyrrole (95) happens with ease. A stable representative of these intermediates 4//-4,4-dimethyl-2-hydroxy-... 

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