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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
Author(s) -
Guerrero Sergio A.,
Ramírez Juan E.,
Palma Alirio,
Cobo Justo,
Glidewell Christopher
Publication year - 2019
Publication title -
acta crystallographica section c
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.304
H-Index - 17
ISSN - 2053-2296
DOI - 10.1107/s2053229619000871
Subject(s) - azepine , chemistry , stereochemistry , supramolecular chemistry , aldol reaction , carboxylate , molecule , organic chemistry , catalysis
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).