A concise and versatile route to tetrahydro-1-benzazepines carrying [a]-fused heterocyclic units: synthetic sequence and spectroscopic characterization, and the molecular and supramolecular structures of one intermediate and two products

A concise, efficient and versatile route from simple starting materials to tricyclic tetrahydro-1-benzazepines carrying [ a ]-fused heterocyclic units is reported. Thus, the easily accessible methyl 2-[(2-allyl-4-chlorophenyl)amino]acetate, (I), was converted, via (2 RS ,4 SR )-7-chloro-2,3,4,5-tetrahydro-1,4-epoxy-1-benzo[ b ]azepine-2-carboxylate, (II), to the key intermediate methyl (2 RS ,4 SR )-7-chloro-4-hydroxy-2,3,4,5-tetrahydro-1 H -benzo[ b ]azepine-2-carboxylate, (III). Chloroacetylation of (III) provided the two regioisomers methyl (2 RS ,4 SR )-7-chloro-1-(2-chloroacetyl)-4-hydroxy-2,3,4,5-tetrahydro-1 H -benzo[ b ]azepine-2-carboxylate, (IV a ), and methyl (2 RS ,4 SR )-7-chloro-4-(2-chloroacetoxy)-2,3,4,5-tetrahydro-1 H -benzo[ b ]azepine-2-carboxylate, C 14 H 15 Cl 2 NO 4 , (IV b ), as the major and minor products, respectively, and further reaction of (IV a ) with aminoethanol gave the tricyclic target compound (4a RS ,6 SR )-9-chloro-6-hydroxy-3-(2-hydroxyethyl)-2,3,4a,5,6,7-hexahydrobenzo[ f ]pyrazino[1,2- a ]azepine-1,4-dione, C 15 H 17 ClN 2 O 4 , (V). Reaction of ester (III) with hydrazine hydrate gave the corresponding carbohydrazide (VI), which, with trimethoxymethane, gave a second tricyclic target product, (4a RS ,6 SR )-9-chloro-6-hydroxy-4a,5,6,7-tetrahydrobenzo[ f ][1,2,4]triazino[4,5- a ]azepin-4(3 H )-one, C 12 H 12 ClN 3 O 2 , (VII). Full spectroscopic characterization (IR, 1 H and 13 C NMR, and mass spectrometry) is reported for each of compounds (I)–(III), (IV a ), (IV b ) and (V)–(VII), along with the molecular and supramolecular structures of (IV b ), (V) and (VII). In each of (IV b ), (V) and (VII), the azepine ring adopts a chair conformation and the six-membered heterocyclic rings in (V) and (VII) adopt approximate boat forms. The molecules in (IV b ), (V) and (VII) are linked, in each case, into complex hydrogen-bonded sheets, but these sheets all contain a different range of hydrogen-bond types: N—H...O, C—H...O, C—H...N and C—H...π(arene) in (IV b ), multiple C—H...O hydrogen bonds in (V), and N—H...N, O—H...O, C—H...N, C—H...O and C—H...π(arene) in (VII).