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A concise, efficient and versatile synthesis of amino‐substituted benzo[b]pyrimido[5,4‐f]azepines is described: starting from a 5‐allyl‐4,6‐dichloropyrimidine, the synthesis involves base‐catalysed aminolysis followed by intramolecular Friedel–Crafts cyclization. Four new amino‐substituted benzo[b]pyrimido[5,4‐f]azepines are reported, and all the products and reaction intermediates have been fully characterized by IR, 1H and 13C NMR spectroscopy and mass spectrometry, and the molecular and supramolecular structures of three products and one intermediate have been determined. In each of N,2,6,11‐tetramethyl‐N‐phenyl‐6,11‐dihydro‐5H‐benzo[b]pyrimido[5,4‐f]azepin‐4‐amine, C22H24N5, (III), 4‐(1H‐benzo[d]imidazol‐1‐yl)‐6,11‐dimethyl‐6,11‐dihydro‐5H‐benzo[b]pyrimido[5,4‐f]azepine, which crystallizes as a 0.374‐hydrate, C21H19N5·0.374H2O, (VIIIa), and 6,7,9,11‐tetramethyl‐4‐(5‐methyl‐1H‐benzo[d]imidazol‐1‐yl)‐6,11‐dihydro‐5H‐benzo[b]pyrimido[5,4‐f]azepine, C24H25N5, (VIIIc), the azepine ring adopts a boat conformation, but with a different configuration at the stereogenic centre in (VIIIc), as compared with (III) and (VIIIa). In the intermediate 5‐allyl‐6‐(1H‐benzo[d]imidazol‐1‐yl)‐N‐methyl‐N‐(4‐methylphenyl)pyrimidin‐4‐amine, C22N21N5, (VIIb), the immediate precursor of 4‐(1H‐benzo[d]imidazol‐1‐yl)‐6,8,11‐trimethyl‐6,11‐dihydro‐5H‐benzo[b]pyrimido[5,4‐f]azepine, (VIIIb), the allyl group is disordered over two sets of atomic sites having occupancies of 0.688 (5) and 0.312 (5). The molecules of (III) are linked into chains by a C—H…π(pyrimidine) hydrogen bond, and those of (VIIb) are linked into complex sheets by three hydrogen bonds, one of the C—H…N type and two of C—H…π(arene) type. The molecules of the organic component in (VIIIa) are linked into a chain of rings by two C—H…π(arene) hydrogen bonds, and these chains are linked into sheets by the water components; a single weak C—H…N hydrogen bond links molecules of (VIIIc) into centrosymmetric R22(10) dimers. Comparisons are made with some related compounds. [ABSTRACT FROM AUTHOR]

Compounds containing the tricyclic dibenzo[b,e]azepine system have potential activity in the treatment of a number of diseases. Continuing with our studies on the synthesis of new small and potentially bioactive molecules, a synthetic route, involving acid-catalysed intramolecular Friedel-Crafts cyclization, to the readily separable diastereoisomers of 11-ethyl-6,11-dihydro-5H-dibenzo[b,e]azepine-6-carboxamide, a potentially useful precursor in the synthesis of analogues of some anti-allergenic, antidepressant and antihistaminic drugs currently in use, has been developed starting from 2-allylphenylamine and methyl 2-bromo-2-phenylacetate and proceeding via racemic methyl 2-[(2-allylphenyl)amino]-2-phenylacetate (A) and racemic 2-[(2-allylphenyl)amino]-2-phenylacetamide (B), to give the two diastereoisomers (I) and (II), C17H18N2O. Isomers (I) and (II), and their precursors (A) and (B), have all been fully characterized spectroscopically. Structure analysis of the minor isomer (I) shows that it has the (6RS,11RS) configuration, and that the azepine ring adopts a conformation intermediate between the boat and twist-boat forms, with the carboxamide and ethyl substituents both occupying quasi-equatorial sites. The molecules of (I) are linked by a combination of N-H…O, N-H…π(arene) and C-H…π(arene) hydrogen bonds to form complex sheets. Comparisons are made with the structures of some related compounds. [ABSTRACT FROM AUTHOR]

Tetrahydro-1-benzazepines have been described as potential antiparasitic drugs for the treatment of chagas disease and leishmaniasis, two of the most important so-called `forgotten tropical diseases' affecting South and Central America, caused by Trypanosoma cruzi and Leishmania chagasi parasites, respectively. Continuing our extensive work describing the structural characteristics of some related compounds with interesting biological properties, the crystallographic features of three epoxy-1-benzazepines, namely (2 SR,4 RS)-6,8-dimethyl-2-(naphthalen-1-yl)-2,3,4,5-tetrahydro-1 H-1,4-epoxy-1-benzazepine, (1), (2 SR,4 RS)-6,9-dimethyl-2-(naphthalen-1-yl)-2,3,4,5-tetrahydro-1 H-1,4-epoxy-1-benzazepine, (2), and (2 SR,4 RS)-8,9-dimethyl-2-(naphthalen-1-yl)-2,3,4,5-tetrahydro-1 H-1,4-epoxy-1-benzazepine, (3), all C22H21NO, and two 1-benzazepin-4-ols, namely 7-fluoro- cis-2-[( E)-styryl]-2,3,4,5-tetrahydro-1 H-1-benzazepin-4-ol, C18H18FNO, (4), and 7-fluoro- cis-2-[( E)-pent-1-enyl]-2,3,4,5-tetrahydro-1 H-1-benzazepin-4-ol, C15H20FNO, (5), are described. Some peculiarities in the crystallization behaviour were found, involving significant variations in the crystalline structures as a result of modest changes in the peripheral substituents in (1)-(3) and the occurrence of discrete disorder due to the molecular overlay of enantiomers with more than one conformation in (5). In particular, an interesting phase change on cooling was observed for compound (5), accompanied by an approximate fourfold increase of the unit-cell volume and a change of the Z′ value from 1 to 4. This transition is a consequence of the partial ordering of the pentenyl chains in half of the molecules breaking half of the symmetry axes observed in the room-temperature structure of (5). The structural assembly in all the title compounds is characterized by not only (N,O)-H...(O,N) hydrogen bonds, but also by unconventional C-H...O contacts, resulting in a wide diversity of packing. [ABSTRACT FROM AUTHOR]

A simple and effective two-step approach to tricyclic pyrimidine-fused benzazepines has been adapted to give the tetracyclic analogues. In ( RS)-8-chloro-6-methyl-1,2,6,7-tetrahydropyrimido[5′,4′:6,7]azepino[3,2,1- hi]indole, C15H14ClN3, (I), the five-membered ring adopts an envelope conformation, as does the reduced pyridine ring in ( RS)-9-chloro-7-methyl-2,3,7,8-tetrahydro-1 H-pyrimido[5′,4′:6,7]azepino[3,2,1- ij]quinoline, C16H16ClN3, (II). However, the seven-membered rings in (I) and (II) adopt very different conformations, with the result that the methyl substituent occupies a quasi-axial site in (I) but a quasi-equatorial site in (II). The molecules of (I) are linked by C-H...N hydrogen bonds to form C(5) chains and inversion-related pairs of chains are linked by a π-π stacking interaction. A combination of a C-H...π hydrogen bond and two C-Cl...π interactions links the molecules of (II) into complex sheets. Comparisons are made with some similar fused heterocyclic compounds. [ABSTRACT FROM AUTHOR]