title: Salt forms of the pharmaceutical amide dihydrocarbamazepine.
abstract: Carbamazepine (CBZ) is well known as a model active pharmaceutical ingredient used in the study of polymorphism and the generation and comparison of cocrystal forms. The pharmaceutical amide dihydrocarbamazepine (DCBZ) is a less well known material and is largely of interest here as a structural congener of CBZ. Reaction of DCBZ with strong acids results in protonation of the amide functionality at the O atom and gives the salt forms dihydrocarbamazepine hydrochloride {systematic name: [(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)(hydroxy)methylidene]azanium chloride, C15H15N2O(+)·Cl(-)}, dihydrocarbamazepine hydrochloride monohydrate {systematic name: [(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)(hydroxy)methylidene]azanium chloride monohydrate, C15H15N2O(+)·Cl(-)·H2O} and dihydrocarbamazepine hydrobromide monohydrate {systematic name: [(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)(hydroxy)methylidene]azanium bromide monohydrate, C15H15N2O(+)·Br(-)·H2O}. The anhydrous hydrochloride has a structure with two crystallographically independent ion pairs (Z' = 2), wherein both cations adopt syn conformations, whilst the two hydrated species are mutually isostructural and have cations with anti conformations. Compared to neutral dihydrocarbamazepine structures, protonation of the amide group is shown to cause changes to both the molecular (C=O bond lengthening and C-N bond shortening) and the supramolecular structures. The amide-to-amide and dimeric hydrogen-bonding motifs seen for neutral polymorphs and cocrystalline species are replaced here by one-dimensional polymeric constructs with no direct amide-to-amide bonds. The structures are also compared with, and shown to be closely related to, those of the salt forms of the structurally similar pharmaceutical carbamazepine.
authors: Westchem, Department of Pure & Applied Chemistry, University of Strathclyde, 295 Cathedral Street, Glasgow G1 1XL, Scotland.
authors: Amanda R
authors: AR
authors: Buist
authors: Westchem, Department of Pure & Applied Chemistry, University of Strathclyde, 295 Cathedral Street, Glasgow G1 1XL, Scotland.
authors: Alan R
authors: AR
authors: Kennedy
mesh_terms: D000577:Amides / Q000737:chemistry*; D001381:Azepines / Q000737:chemistry*; D002220:Carbamazepine / Q000737:chemistry* / Q000494:pharmacology; D003460:Crystallization; D018360:Crystallography, X-Ray; D006860:Hydrogen Bonding; D015394:Molecular Structure
chemical_list: C000608672:((10,11-dihydro-5H-dibenzo(b,f)azepin-5-yl)(hydroxy)methylidene)azanium chloride; D000577:Amides; D001381:Azepines; D002220:Carbamazepine
keywords: active pharmaceutical ingredients; crystal structure; dihydrocarbamazepine; pharmaceutical chemistry; protonated amide; resonance forms; salt selection