Guerrero Sergio A, Ramírez Juan E, Palma Alirio, Cobo Justo, Glidewell Christopher
Laboratorio de Síntesis Orgánica, Escuela de Química, Universidad Industrial de Santander, AA 678, Bucaramanga, Colombia.
Departamento de Química Inorgánica y Orgánica, Universidad de Jaén, 23071 Jaén, Spain.
Acta Crystallogr C Struct Chem. 2019 Feb 1;75(Pt 2):168-177. doi: 10.1107/S2053229619000871. Epub 2019 Jan 25.
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 (2RS,4SR)-7-chloro-2,3,4,5-tetrahydro-1,4-epoxy-1-benzo[b]azepine-2-carboxylate, (II), to the key intermediate methyl (2RS,4SR)-7-chloro-4-hydroxy-2,3,4,5-tetrahydro-1H-benzo[b]azepine-2-carboxylate, (III). Chloroacetylation of (III) provided the two regioisomers methyl (2RS,4SR)-7-chloro-1-(2-chloroacetyl)-4-hydroxy-2,3,4,5-tetrahydro-1H-benzo[b]azepine-2-carboxylate, (IVa), and methyl (2RS,4SR)-7-chloro-4-(2-chloroacetoxy)-2,3,4,5-tetrahydro-1H-benzo[b]azepine-2-carboxylate, CHClNO, (IVb), as the major and minor products, respectively, and further reaction of (IVa) with aminoethanol gave the tricyclic target compound (4aRS,6SR)-9-chloro-6-hydroxy-3-(2-hydroxyethyl)-2,3,4a,5,6,7-hexahydrobenzo[f]pyrazino[1,2-a]azepine-1,4-dione, CHClNO, (V). Reaction of ester (III) with hydrazine hydrate gave the corresponding carbohydrazide (VI), which, with trimethoxymethane, gave a second tricyclic target product, (4aRS,6SR)-9-chloro-6-hydroxy-4a,5,6,7-tetrahydrobenzo[f][1,2,4]triazino[4,5-a]azepin-4(3H)-one, CHClNO, (VII). Full spectroscopic characterization (IR, H and C NMR, and mass spectrometry) is reported for each of compounds (I)-(III), (IVa), (IVb) and (V)-(VII), along with the molecular and supramolecular structures of (IVb), (V) and (VII). In each of (IVb), (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 (IVb), (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 (IVb), 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).
报道了一种从简单起始原料到带有[a]-稠合杂环单元的三环四氢-1-苯并氮杂卓的简洁、高效且通用的路线。因此，易于获得的2-[(2-烯丙基-4-氯苯基)氨基]乙酸甲酯（I），通过(2RS,4SR)-7-氯-2,3,4,5-四氢-1,4-环氧-1-苯并[b]氮杂卓-2-羧酸酯（II），转化为关键中间体(2RS,4SR)-7-氯-4-羟基-2,3,4,5-四氢-1H-苯并[b]氮杂卓-2-羧酸甲酯（III）。（III）的氯乙酰化反应分别提供了两种区域异构体，即主要产物(2RS,4SR)-7-氯-1-(2-氯乙酰基)-4-羟基-2,3,4,5-四氢-1H-苯并[b]氮杂卓-2-羧酸甲酯（IVa）和次要产物(2RS,4SR)-7-氯-4-(2-氯乙酰氧基)-2,3,4,5-四氢-1H-苯并[b]氮杂卓-2-羧酸甲酯（IVb），并且（IVa）与氨基乙醇的进一步反应得到了三环目标化合物(4aRS,6SR)-9-氯-6-羟基-3-(2-羟乙基)-2,3,4a,5,6,7-六氢苯并[f]吡嗪并[1,2-a]氮杂卓-1,4-二酮（V）。酯（III）与水合肼反应得到相应的碳酰肼（VI），其与三甲氧基甲烷反应得到了第二种三环目标产物(4aRS,6SR)-9-氯-6-羟基-4a,5,6,7-四氢苯并[f][1,2,4]三嗪并[4,5-a]氮杂卓-4(3H)-酮（VII）。报道了化合物（I）-（III）、（IVa）、（IVb）和（V）-（VII）各自的完整光谱表征（红外光谱、氢谱和碳谱以及质谱），以及（IVb）、（V）和（VII）的分子和超分子结构。在（IVb）、（V）和（VII）中的每一种中，氮杂卓环呈椅式构象且（V）和（VII）中的六元杂环呈近似船式构象。（IVb）、（V）和（VII）中的分子在每种情况下都连接成复杂氢键片层，但这些片层都包含不同范围的氢键类型：（IVb）中的N-H...O、C-H...O、C-H...N和C-H...π(芳烃)，（V）中的多个C-H...O氢键，以及（VII）中的N-H...N、O-H...O、C-H...N、C-H...O和C-H...π(芳烃)。
