Salt forms of amides: protonation and polymorphism of carbamazepine and cytenamide

Amanda Buist, Alan Kennedy, Kenneth Shankland, Norman Shankland, Mark J. Spillman

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

In situ generation of HCl or HBr in alcohol leads to O-protonation of the
amide group of carbamazepine. Six salt phases have been produced using this method and their crystal structures determined by single crystal diffraction. A new polymorph of carbamazepine hydrochloride is described as are two polymorphs of carbamazepine hydrobromide. All are protonated at the amide O atom to give RC(OH)NH2 cations. Prolonged exposure to air results in addition of water to the solid salt forms. Such hydration of carbamazepine hydrobromide simply gives a monohydrated phase, but similar treatment of the equivalent hydrochloride results in partial loss of HCl and the transfer of the remaining proton from the amide group to water to give [carbamazepine][H3O]0.5[Cl]0.5·H2O. A similar hydronium chloride species is the only
product isolated after reaction of the carbamazepine analogue cytenamide with HCl generated in methanol.
LanguageEnglish
Pages5121-5127
Number of pages7
JournalCrystal Growth and Design
Volume13
Issue number11
Early online date7 Oct 2013
DOIs
Publication statusPublished - 2013

Fingerprint

hydrobromides
Protonation
polymorphism
Carbamazepine
hydrochlorides
Polymorphism
Amides
amides
Salts
salts
Hydration
water
hydration
Water
Protons
Methanol
alcohols
Alcohols
methyl alcohol
Diffraction

Cite this

Buist, Amanda ; Kennedy, Alan ; Shankland, Kenneth ; Shankland, Norman ; Spillman, Mark J. / Salt forms of amides : protonation and polymorphism of carbamazepine and cytenamide. In: Crystal Growth and Design. 2013 ; Vol. 13, No. 11. pp. 5121-5127.
@article{358b488e1b4f47f7b0902e50d5cd9493,
title = "Salt forms of amides: protonation and polymorphism of carbamazepine and cytenamide",
abstract = "In situ generation of HCl or HBr in alcohol leads to O-protonation of theamide group of carbamazepine. Six salt phases have been produced using this method and their crystal structures determined by single crystal diffraction. A new polymorph of carbamazepine hydrochloride is described as are two polymorphs of carbamazepine hydrobromide. All are protonated at the amide O atom to give RC(OH)NH2 cations. Prolonged exposure to air results in addition of water to the solid salt forms. Such hydration of carbamazepine hydrobromide simply gives a monohydrated phase, but similar treatment of the equivalent hydrochloride results in partial loss of HCl and the transfer of the remaining proton from the amide group to water to give [carbamazepine][H3O]0.5[Cl]0.5·H2O. A similar hydronium chloride species is the onlyproduct isolated after reaction of the carbamazepine analogue cytenamide with HCl generated in methanol.",
author = "Amanda Buist and Alan Kennedy and Kenneth Shankland and Norman Shankland and Spillman, {Mark J.}",
year = "2013",
doi = "10.1021/cg401341y",
language = "English",
volume = "13",
pages = "5121--5127",
journal = "Crystal Growth and Design",
issn = "1528-7483",
publisher = "American Chemical Society",
number = "11",

}

Salt forms of amides : protonation and polymorphism of carbamazepine and cytenamide. / Buist, Amanda; Kennedy, Alan; Shankland, Kenneth; Shankland, Norman; Spillman, Mark J.

In: Crystal Growth and Design, Vol. 13, No. 11, 2013, p. 5121-5127.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Salt forms of amides

T2 - Crystal Growth and Design

AU - Buist, Amanda

AU - Kennedy, Alan

AU - Shankland, Kenneth

AU - Shankland, Norman

AU - Spillman, Mark J.

PY - 2013

Y1 - 2013

N2 - In situ generation of HCl or HBr in alcohol leads to O-protonation of theamide group of carbamazepine. Six salt phases have been produced using this method and their crystal structures determined by single crystal diffraction. A new polymorph of carbamazepine hydrochloride is described as are two polymorphs of carbamazepine hydrobromide. All are protonated at the amide O atom to give RC(OH)NH2 cations. Prolonged exposure to air results in addition of water to the solid salt forms. Such hydration of carbamazepine hydrobromide simply gives a monohydrated phase, but similar treatment of the equivalent hydrochloride results in partial loss of HCl and the transfer of the remaining proton from the amide group to water to give [carbamazepine][H3O]0.5[Cl]0.5·H2O. A similar hydronium chloride species is the onlyproduct isolated after reaction of the carbamazepine analogue cytenamide with HCl generated in methanol.

AB - In situ generation of HCl or HBr in alcohol leads to O-protonation of theamide group of carbamazepine. Six salt phases have been produced using this method and their crystal structures determined by single crystal diffraction. A new polymorph of carbamazepine hydrochloride is described as are two polymorphs of carbamazepine hydrobromide. All are protonated at the amide O atom to give RC(OH)NH2 cations. Prolonged exposure to air results in addition of water to the solid salt forms. Such hydration of carbamazepine hydrobromide simply gives a monohydrated phase, but similar treatment of the equivalent hydrochloride results in partial loss of HCl and the transfer of the remaining proton from the amide group to water to give [carbamazepine][H3O]0.5[Cl]0.5·H2O. A similar hydronium chloride species is the onlyproduct isolated after reaction of the carbamazepine analogue cytenamide with HCl generated in methanol.

UR - http://www.scopus.com/inward/record.url?scp=84887723780&partnerID=8YFLogxK

UR - http://pubs.acs.org/journal/cgdefu

U2 - 10.1021/cg401341y

DO - 10.1021/cg401341y

M3 - Article

VL - 13

SP - 5121

EP - 5127

JO - Crystal Growth and Design

JF - Crystal Growth and Design

SN - 1528-7483

IS - 11

ER -