31295-34-8Relevant articles and documents
Transforming aspirin into novel molecular salts of salicylic acid
Andre, Vania,Martins, Ines,Quaresma, Silvia,Martins, Marta,Duarte, M. Teresa
, p. 707 - 714 (2014/06/09)
Aspirin is one of the most widely used analgesic, antipyretic, and anti-inflammatory drugs. Herein we disclose a way to transform aspirin into novel multicomponent crystal forms of salicylic acid, also a long-known analgesic with anti-inflammatory properties, among others, covering a broad spectrum of applications, including skin care products. A salicylic acid:salicylate ammonium salt and a salicylate:2-methyl-4-oxopentan-2-aminium molecular salt are concomitantly formed in acetone/ammonia solutions, resulting from aspirin decomposition. Furthermore the 2-methyl-4-oxopentan-2-aminium cation results from a sequence of in situ reactions: (i) imine formation, in which acetone is known to undergo under basic pH conditions; (ii) nucleophilic attack of α-carbon of the deprotonated acetone to the imine yielding 4-amino-4-methylpentan-2-one; and (iii) protonation of 4-amino-4-methylpentan-2- one. In the structures obtained for the novel multicomponent crystal forms, the strong charge-assisted N+-H···O/O- hydrogen bonds between the drug molecule and the co-former play a key function in the supramolecular arrangement. The typical R22(8) carboxylic···carboxylic homosynthon observed in salicylic acid was inhibited by the salt formation. These results are in agreement with the results of a careful survey on the Cambridge Structural Database. Graphical abstract: [Figure not available: see fulltext.]
