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Crystal structure of guaifenesin, 3-(2-methoxyphenoxy)-1,2-propanediol

Published online by Cambridge University Press:  06 March 2012

James A. Kaduk
James A. Kaduk*
Affiliation:
BP Chemicals, P.O. Box 3011 MC F-9, Naperville, Illinois 60566
*
a)Author to whom correspondence should be addressed; Electronic mail: kadukja@bp.com
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Abstract

The crystal structure of the common expectorant guaifenesin, 3-(2-methoxyphenoxy)-1, 2-propanediol (C10H14O4) was solved by applying Monte Carlo simulated annealing techniques to synchrotron powder data, and refined using the Rietveld method. Initial structure solutions yielded an unreasonable conformation, and an unacceptable refinement. Quantum chemical geometry optimizations were used to identify the correct conformation. Guaifenesin crystallizes in the orthorhombic space group P212121 (#19), with a=7.657 05(7), b=25.670 20(24), c=4.979 66(4) Å, V=978.79(2) Å3, and Z=4. Both hydroxyl groups act as hydrogen bond donors and acceptors, resulting in the formation of a two-dimensional network of strong hydrogen bonds in the ac plane. The solid state conformation is ∼4 kcal/mol higher in energy than the minimum-energy conformation of an isolated molecule, but the formation of the hydrogen bonds results in an energy gain of ∼100 kcal/mol. Knowledge of the crystal structure permits quantitative phase analysis of guaifenesin-containing pharmaceuticals (such as Duratuss GP 120-1200) by the Rietveld method.

Type
Technical Articles
Information
Powder Diffraction , Volume 19 , Issue 2 , June 2004 , pp. 127 - 132
Copyright
Copyright © Cambridge University Press 2004

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