Three closely related dibenzazepine carboxylic acids: hydrogen-bonded aggregation in one, two and three dimensions

Sanabria, Carlos M.; Palma, Alirio; Cobo, Justo; Glidewell, Christopher

doi:10.1107/s2053229614003568

Cited by 4 publications

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References 37 publications

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“…The boat conformation found here for the azepine ring in (I)-(V) has been similarly observed in a series of dibenzo- (Yousuf et al, 2012;Abdoh et al, 2013;Manjunath, Vinay Kumar et al, 2013;, although the azepine conformation in a series of dibenzo[b,e]azepine derivatives was found to be intermediate between the boat and twist-boat forms (Sanabría et al, 2014).…”

Section: Figuresupporting

confidence: 75%

Five closely related 4-chloro-6,11-dihydro-5H-benzo[b]pyrimido[5,4-f]azepines: similar molecular structures but different supramolecular assemblies

et al. 2015

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Dibenz[b,f]azepine (DBA) is a privileged 6-7-6 tricyclic ring system of importance in both organic and medicinal chemistry. Benzo[b]pyrimido[5,4-f]azepines (BPAs), which also contain a privileged 6-7-6 ring system, are less well investigated, probably because of a lack of straightforward and versatile methods for their synthesis. A simple and versatile synthetic approach to BPAs based on intramolecular Friedel-Crafts alkylation has been developed. A group of closely-related benzo[b]pyrimido[5,4-f]azepine derivatives, namely (6RS)-4-chloro-6,11-dimethyl-6,11-dihydro-5H-benzo[b]pyrimido[5,4-f]azepine, C14H14ClN3, (I), (6RS)-4-chloro-8-hydroxy-6,11-dimethyl-6,11-dihydro-5H-benzo[b]pyrimido[5,4-f]azepine, C14H14ClN3O, (II), (6RS)-4-chloro-8-methoxy-6,11-dimethyl-6,11-dihydro-5H-benzo[b]pyrimido[5,4-f]azepine, C15H16ClN3O, (III), and (6RS)-4-chloro-8-methoxy-6,11-dimethyl-2-phenyl-6,11-dihydro-5H-benzo[b]pyrimido[5,4-f]azepine, C21H20ClN3O, (IV), has been prepared and their structures compared with the recently published structure [Acosta-Quintero et al. (2015). Eur. J. Org. Chem. pp. 5360-5369] of (6RS)-4-chloro-2,6,8,11-tetramethyl-6,11-dihydro-5H-benzo[b]pyrimido[5,4-f]azepine, (V). All five compounds crystallize as racemic mixtures and they have very similar molecular conformations, with the azepine ring adopting a boat-type conformation in each case, although the orientation of the methoxy substituent in each of (III) and (IV) is different. The supramolecular assemblies in (II) and (IV) depend upon hydrogen bonds of the O-H...N and C-H...π(arene) types, respectively, those in (I) and (V) depend upon π-π stacking interactions involving pairs of pyrimidine rings, and that in (III) depends upon a π-π stacking interaction involving pairs of phenyl rings. Short C-Cl...π(pyrimidine) contacts are present in (I), (II) and (IV) but not in (III) or (V).

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Section: Figuresupporting

confidence: 75%

Five closely related 4-chloro-6,11-dihydro-5H-benzo[b]pyrimido[5,4-f]azepines: similar molecular structures but different supramolecular assemblies

et al. 2015

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“…For the seven-membered ring in each of (I), (II) and the major form of (III), the ring conformations are dominated by the twist-boat sin form 2 (Evans & Boeyens, 1989). By contrast, the most common conformation of the seven-membered ring in tricyclic dibenzazepines is one intermediate between the boat and twistboat forms (Sanabría et al, 2014), while the most common form in benzopyrimidoazepines is the boat form (cos form 2) .…”

Section: Resultsmentioning

confidence: 99%

Three tetracyclic dibenzoazepine derivatives exhibiting different molecular conformations, different patterns of intermolecular hydrogen bonding and different modes of supramolecular aggregation

et al. 2017

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The biological potential of compounds of the tricyclic dibenzo[b,e]azepine system has resulted in considerable synthetic efforts to develop efficient methods for the synthesis of new derivatives of this kind. (9RS,15RS)-9-Ethyl-11-methyl-9,13b-dihydrodibenzo[c,f]thiazolo[3,2-a]azepin-3(2H)-one, CHNOS, (I), crystallizes as a kryptoracemate with Z' = 2 in the space group P2, with one molecule each of the (9R,15R) and (9S,15S) configurations in the asymmetric unit, while (9RS,15RS)-9-ethyl-7,12-dimethyl-9,13b-dihydrodibenzo[c,f]thiazolo[3,2-a]azepin-3(2H)-one, CHNOS, (II), crystallizes with Z' = 1 in the space group C2/c. Ethyl (13RS)-2-chloro-13-ethyl-4-oxo-8,13-dihydro-4H-benzo[5,6]azepino[3,2,1-ij]quinoline-5-carboxylate, CHClNO, (III), exhibits enantiomeric disorder in the space group P-1 such that the reference site is occupied by the 13R and 13S enantiomers, with occupancies of 0.900 (6) and 0.100 (6). In each of the two independent molecules in (I), the five-membered ring adopts an envelope conformation, but the corresponding ring in (II) adopts a half-chair conformation, while the six-membered ring in the major form of (III) adopts a twist-boat conformation. The conformation of the seven-membered ring in each of (I), (II) and the major form of (III) approximates to the twist-boat form. The molecules of compound (I) are linked by two C-H...O hydrogen bonds to form two independent antiparallel C(5) chains, with each type containing only one enantiomer. These chains are linked into sheets by two C-H...π(arene) hydrogen bonds, in which the two donors are both provided by the (9R,15R) enantiomer and the two acceptor arene rings form part of a molecule of (9S,15S) configuration, precluding any additional crystallographic symmetry. The molecules of compound (II) are linked by inversion-related C-H...π(arene) hydrogen bonds to form isolated cyclic centrosymmetric dimers. The molecules of compound (III) are linked into cyclic centrosymmetric dimers by C-H...O hydrogen bonds and these dimers are linked into chains by a π-π stacking interaction. Comparisons are made with some related structures.

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“…In contrast to the chair conformations reported here, we note that in 12 variously substituted examples of the tricyclic benzo[b]pyrimido[5,4-f]azepine system, the azepine ring always adopts a boat conformation (Acosta et al, 2015;Acosta Quintero et al, 2016a,b, 2018, as does the azepine ring in a dibenzo[b,e]azepine-6-carboxamide. On the other hand, in three closely related dibenzo[b,e]azepine-6-carboxylic acids, the azepine rings adopt conformations intermediate between boat and twist-boat forms (Sanabría et al, 2014).…”

Section: Figurementioning

confidence: 99%

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

et al. 2019

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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, C14H15Cl2NO4, (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, C15H17ClN2O4, (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, C12H12ClN3O2, (VII). Full spectroscopic characterization (IR, 1H and 13C 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).

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Three closely related dibenzazepine carboxylic acids: hydrogen-bonded aggregation in one, two and three dimensions

Cited by 4 publications

References 37 publications

Five closely related 4-chloro-6,11-dihydro-5H-benzo[b]pyrimido[5,4-f]azepines: similar molecular structures but different supramolecular assemblies

Five closely related 4-chloro-6,11-dihydro-5H-benzo[b]pyrimido[5,4-f]azepines: similar molecular structures but different supramolecular assemblies

Three tetracyclic dibenzoazepine derivatives exhibiting different molecular conformations, different patterns of intermolecular hydrogen bonding and different modes of supramolecular aggregation

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

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