Pyrroles heterocyclic derivatives

The halogenoacetyl derivatives of pyrrole and indole undergo normal nucleophilic substitution reactions and with bifunctional nucleophiles they yield the expected heterocyclic derivatives, as, for example, in the formation of the thiazolylindole from the reaction of 3-(chloroacetyl)indole with thioacetamide (77IJC(B)473>. 

Bicyclic systems. The benzo-fused pyrrole heterocycles 13-15 are analogues of naphthalene with carba-zole 16 having an electronic relationship to phenanthrene. The systematic names show the position of the benzenoid ring but the common names indolizine 13, indole 14, isoindole 15, and carbazole 16 (Figure 1) are still widely used. The benzo derivatives of furan and thiophene are named in a similar manner, but their common names have largely fallen into disuse. For the benzo[7>] systems 17 and 20, the [b is commonly omitted. 

Five-membered heterocycles Most papers dealing with the synthesis of cyclic compounds with 10 report on the formation of six-membered or condensed heterocyclic systems. Nevertheless, a number of new five-membered heterocyclic derivatives have been described. So furane, thiophene and pyrrole derivatives were prepared by ring enlargement when oxiranes, thiirane and A -tosylhydrazide, respectively, were reacted with 10 at -10 Various other ways to prepare pyrrole derivatives include cyclization of amino... 

C.i.d. Heck Reaction. 7r-Deflcient chloropyrazines can be Heck-coupled into 1,3-azoles (Scheme 50). It will be recalled that the same methodology was used to couple into the TT-excessive furan, thiophene, and pyrrole heterocycles and their benzo derivatives (vide supra). The Heck reaction in oxazole and thiazole proceeds in a regiospeciflc manner. The new carbon-carbon bond is formed in the 5-position 117 next to the ether heteroatom as commonly observed in vinyl ethers and strongly favored in furan and thiophene. In benzoxazole and benzothiazole the only vacant position is between the two heteroatoms, and the Heck coupling results in substitution into the 2-position 118. " ... 

Pyrrole containing heterocyclic derivatives have been reported as having important biological activities such as COX-1/COX-2 inhibitors and cytotoxic activity against a variety of marine and human tximor models (Figure 4) [84]. 

Laviron, Person, and Fournari [87] confirmed this form of reduction for the oximes of neutral aromatic and heterocyclic derivatives (furan, pyrrole), whereas basic heterocyclic derivatives (pyridine) only gave a two-electron wave for the unprotonated compound. Four-... 

Cyclic compounds that contain at least one atom other than carbon within their ring are called heterocyclic compounds, and those that possess aromatic stability are called het erocyclic aromatic compounds Some representative heterocyclic aromatic compounds are pyridine pyrrole furan and thiophene The structures and the lUPAC numbering system used m naming their derivatives are shown In their stability and chemical behav lor all these compounds resemble benzene more than they resemble alkenes... 

Furan and thiophene undergo addition reactions with carbenes. Thus cyclopropane derivatives are obtained from these heterocycles on copper(I) bromide-catalyzed reaction with diazomethane and light-promoted reaction with diazoacetic acid ester (Scheme 41). The copper-catalyzed reaction of pyrrole with diazoacetic acid ester, however, gives a 2-substituted product (Scheme 42). 

The methods outlined, of course, are readily applicable to a wide variety of substituted heterocycles like the carboxyl, hydroxy and mercapto derivatives of pyridines, pyridine 1-oxides, pyrroles, etc. The application to amines and to diaza compounds such as pyrimidine, where the two centers are basic, is obvious except that now 23 takes the role of the neutral compound, 21 and 22 the roles of the tautomeric first conjugate bases, and 20 the role of the second conjugate base. Extensions to molecules with more than two acidic or basic centers, such as aminonicotinic acid, pyrimidinecarboxylic acids, etc., are obvious although they tend to become algebraically cumbersome, involving (for three centers) three measurable Kg s, four Ay s, and fifteen ideal dissociation constants (A ), a total of twenty-two constants of which seven are independent. 

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