The reaction of 4-(3,4-dimethoxyphenyl)-5-aminopyrazoles 7A-D with aromatic and heterocyclic aldehydes in strong acidic media (trifluoroacetic or formic acid) has been studied. The initial azomethine derivatives 8 undergo cyclization similar to the Pictet-Spengler condensation to form the intermediate 4,5-dihydroisoquinolines 9 which readily dehydrogenate giving 5-aryl(heteroaryl)-pyrazolo[3,4-c]isoquinoline derivatives 10 as the final products. Whereas for benzaldehyde and its derivatives this one-pot synthesis presents a convenient general route to 5-aryl-pyrazolo[3,4-c]isoquinolines 10, in the case of heterocyclic aldehydes the product structure varies markedly with the structure of the aldehyde used: (i) 3-pyridyl-, 3-quinolyl-, 3-thienyl-, and 1,2,3-thiadiazolyl-5-carboxaldehydes give 5-heteroarylpyrazolo[3,4-c]isoquinolines; (ii) 1-methylbenzimidazolyl-2-carboxaldehyde gives only intermediate azomethine 8Dh, which does not cyclize; (iii) 1-R-3-indolylcarboxaldehydes (R = H, CH3, CH2Ph) eliminate the heteroaryl fragment resulting in 5-unsubstituted pyrazolo[3,4-c]isoquinolines 11. Thienyl-2-carboxaldehyde reacts by both pathways (i) and (iii) depending on the reaction conditions. The single crystal X-ray structures for 10Dj, 10Cd and 11D provide confirmation of the different types of products formed in these reactions. Mechanisms which explain these transformations are presented.
The convenient one pot synthesis of pyrazolo [3,4-c]isoquinolines 1 from 5-aminopyrazoles 2 and paraformaldehyde in formic or trifluoroacetic acids is described.J. Heterocyclic Chem., 38, 523 (2001).Pyrazolo [3,4-c]isoquinolines are a structurally rare but biologically promising class of heterocyclic compounds containing the pyrazolopyridine core. Closely related pyrazolopyridine derivatives have been extensively studied due to their wide ranging biological activity, such as anxyolitic [1] and antidepressant activities [2], and platelet aggregation inhibition [3]. Therefore, new convenient synthetic routes to similar systems are of considerable interest, and a one-pot transformation of 6-nitroquinoline into pyrazolo [3,4-f]quinolines by the action of aromatic hydrazones/NaH in N,N-dimethylformamide was recently reported [4].Earlier we described [5] the synthesis of 5-unsubstituted pyrazolo [5,4-c]isoquinolines 1 by reaction of 5-aminopyrazoles 2 with tris(morpholino)methane (TMM) in DMF resulting in amidines 3 which underwent cyclization in trifluoroacetic acid (Scheme 1).This method has been found to be very sensitive to the purity of starting compounds. We have also noted that the presence of traces of water in the azolylformamidines cyclization step (3 → 1) results in their facile hydrolysis to 2 which substantially decreases the yield and purity of the products 1. Moreover, this method (Scheme 1) is unsuitable for cyclization of 1-unsubstituted 5-aminopyrazole derivatives (2, R 2 = H): the final products in this case are tris(amino)methanes 4 which are stable in acidic conditions and do not undergo further cyclization [6].As a part of our contribution to poly(aza)heterocyclic systems with potential biological activity [5,7], we describe here a new, convenient, one pot method for the synthesis of 5-unsubstituted pyrazolo [3,4-c]
Treatment of N-phenyl-2-(1-R-indol-3-yl)succinirnides with acetyl perchlorate leads to acylation of the benzene ring of the indole substituent.In a previous publication was reported the synthesis and reactions of 2-oxo-5-alkyi-3-phenyl-7,8-dimethoxybenzo[c]-pyrrolo[3,2-e]pyrilium perchlorates which were obtained by acylation of N-phenyl-2-(3,4-dimethoxyphenyl)succinimide with alkanoyl perchlorates [1][2][3]. It was shown that reaction of the salts obtained with nitrogen containing mono-and binucleophiles gives high yields of functionally substituted hetero-and carbocyclic compounds (isoquinolines, benzo-2,3-diazepin-4(5H)-ones, and 1,3-aminoaphthols). Such a variety in the reactions of the benzo[c]pyrrolo[3,2-e]pyrilium salts and of derived products dictated our quest to prepare pyrrolo[3,2-e]pyrilium derivatives annelated along the c side with heterocyclic rings. In this work we present the results of the acylation of N-phenyl-2-(1-R-indol-3-yl)succinimides.The starting compounds Ia
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