Salt Forms of Amides: Protonation and Polymorphism of Carbamazepine and Cytenamide

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• 作者：Amanda R. Buist ; Alan R. Kennedy ; Kenneth Shankland ; Norman Shankland ; Mark J. Spillman
• 刊名：Crystal Growth & Design
• 出版年：2013
• 出版时间：November 6, 2013
• 年：2013
• 卷：13
• 期：11
• 页码：5121-5127
• 全文大小：371K
• 年卷期：v.13,no.11(November 6, 2013)
• ISSN：1528-7505

文摘

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路H₂O. A similar hydronium chloride species is the only product isolated after reaction of the carbamazepine analogue cytenamide with HCl generated in methanol.