Hostname: page-component-586b7cd67f-rcrh6 Total loading time: 0 Render date: 2024-11-23T17:33:45.394Z Has data issue: false hasContentIssue false
  • English
  • Français

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: [email protected]
Get access Rights & Permissions [Opens in a new window]

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

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Accelrys, Inc. (2001). Cerius 2, Ver. 4.6MS.Google Scholar
Accelrys, Inc. (2003). Materials Studio 2.2.Google Scholar
Allen, F. A. (2002). “The Cambridge Structural Database: A quarter of a million crystal structures and rising,” Acta Crystallogr., Sect. B: Struct. Sci. ASBSDK B58, 380–388. acl, ASBSDK CrossRefGoogle Scholar
Blanchard, F. (1990). “Pseudoephedrine hydrochloride,” ICDD Grant-in-Aid; PDF entry 41-1946.Google Scholar
Boultif, A.and Louër, D. (1991). “Indexing of powder diffraction patterns for low symmetry lattices by the successive dichotomy method,” J. Appl. Crystallogr. JACGAR 24, 987–993. acr, JACGAR CrossRefGoogle Scholar
Eli Lilly and Company (1984). “Guaifenesin” (private communication); PDF entry 35–1889.Google Scholar
Jeffrey, G. A. (1997). An Introduction to Hydrogen Bonding (Oxford University Press, New York).Google Scholar
Kaduk, J. A. (2002). “Use of the Inorganic Crystal Structure Database as a problem solving tool,” Acta Crystallogr., Sect. B: Struct. Sci. ASBSDK B58, 370–379 (AN0607). acl, ASBSDK CrossRefGoogle Scholar
Larson, A. C. and Von Dreele, R. B. (2000). “General Structure Analysis System (GSAS),” Los Alamos National Laboratory report No. LAUR 86–748.Google Scholar
Materials Data, Inc. (1999). SHADOW 4.2.Google Scholar
Mathew, M.and Palenik, G. J. (1977). “The crystal and molecular structures of (+)-pseudoephedrine and (+)-pseudoephedrine hydrochloride,” Acta Crystallogr., Sect. B: Struct. Crystallogr. Cryst. Chem. ACBCAR 33, 1016–1022. acb, ACBCAR CrossRefGoogle Scholar
Segall, M., Lindan, P. L. D., Probert, M. J., Pickard, C. J., Hasnip, P. J., Clark, S. J., and Payne, M. C. (2002). “First-principles simulation: ideas, illustrations, and the CASTEP code,” J. Phys.: Condens. Matter JCOMEL 14, 2717–2743. jcz, JCOMEL Google Scholar
Shervington, L. A.and Shervington, A. (1998). “Guaifenesin,” Analytical Profiles of Drug Substances and Excipients ZZZZZZ 25, 121–164.CrossRefGoogle Scholar
Wavefunction, Inc. (2003). Spartan’04 Windows.Google Scholar