Summary
Methods are described for the laboratory-scale crystallization of “small” organic compounds. The process of crystallization from solution can be used as a purification step in its own right, or to produce crystals for molecular structure determination by single-crystal or powder X-ray diffraction. Both aspects are discussed, with particular emphasis on growing crystals for structure determination in natural product chemistry. The processes detailed for the slow growth of diffraction-quality crystals include solvent selection and solution supersaturation by evaporation, cooling, liquid/vapor diffusion, and thermal gradient methods. Common problems and solutions, including solid-state polymorphism and solvate formation, are highlighted and modern approaches to parallel crystallization and crystal structure determination from X-ray powder diffraction data are also introduced.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Mullin, J. W. (1972) Crystallization techniques, in Crystallization, 2 ed., Butterworths, London, pp. 233–257.
Trease, G. E. and Evans, W. C. (1996) Cell differentiation and ergastic cell contents, in Pharmacognosy, 14 ed., W B Saunders Company Ltd., London, pp. 554–567.
Trease, G. E. and Evans, W. C. (1996) Volatile oils and resins, in Pharmacognosy, 14 ed., W B Saunders Company Ltd., London, pp. 255–292.
Jacques, J., Collet, A., and Wilen, S. H. (1981) Formation and separation of diastereomers, in Enantiomers, Racemates and Resolutions. John Wiley & Sons, New York, pp. 251–368.
Polonsky, J., Prange, T., Pascard, C., Jacquemin, H., and Fournet, A. (1984) Structure (X-ray analysis) of manicoline B, a mixture of two diastereoisomers of a new alkaloid from Dulacia guianensis (Olacaceae). Tetrahedron Lett. 25, 2359–2362.
Ghisalberti, E. L., Jefferies, P. R., Skelton, B. W., White, A. H., and Williams, R. S. F. (1989) A new stereochemical class of bicyclic sesquiter-penes from Eremophila virgata W. V. Fitzg. (Myoporaceae). Tetrahedron 45, 6297–6308.
VanHook, A. (1961) Crystallization in the laboratory and in the plant, in Crystallization Theory and Practice. Reinhold Publishing Corporation, New York, pp. 192–237.
Jacques, J., Collet, A., and Wilen, S. H. (1981) Solution properties of enantiomers and their mixtures, in Enantiomers, Racemates and Resolutions. John Wiley & Sons, New York, pp. 167–213.
Jacques, J., Collet A., and Wilen, S. H. (1981) Resolution by direct crystallization, in Enantiomers, Racemates and Resolutions. John Wiley & Sons, New York, pp. 217–250.
Threlfall, T. L. (1995) Analysis of organic polymorphs. Analyst 120, 2435–2460.
Glusker, J. P., Lewis, M., and Rossi, M. (1994) Crystals, in Crystal Structure Analysis for Chemists and Biologists. VCH Publishers Inc., New York, pp. 33–72.
Stout, G. H. and Jensen, L. H. (1989) Crystals and their properties, in X-ray Structure Determination. A Practical Guide. John Wiley & Sons, New York, pp. 74–92.
Glusker, J. P. and Trueblood, K. N. (1985) Crystals, in Crystal Structure Analysis. A Primer. Oxford University Press, New York, pp. 8–19.
Watkin, D. J. (1972) A simple small-scale recrystallization apparatus. J. Appl. Crystallogr. 5, 250.
van der Sluis, P., Hezemans, A. M. F., and Kroon, J. (1989) Crystallization of low-molecular-weight organic compounds for X-ray crystallography. J. Appl. Crystallogr. 22, 340–344.
Mullin, J. W. (1972) The crystalline state, in Crystallization, 2 ed., Butter-worths, London, pp. 1–27.
Seigler, D. S. and Brinker, A. M. (1993) Characterisation of cyanogenic glycosides, cyanolipids, nitroglycosides, organic nitro compounds and nitrile glucosides from plants, in Methods in Plant Biochemistry, vol. 8, Alkaloids and Sulphur Compounds (Waterman, P. G., ed., Dey, P. M. and Harborne, J. B. series eds.), Academic Press, London, pp. 51–131.
Trease, G. E. and Evans, W. C. (1996) Introduction and general methods, in Pharmacognosy, 14 ed., W B Saunders Company Ltd., London, pp. 119–130.
Mullin, J. W. (1972) Crystallization kinetics, in Crystallization, 2 ed., Butterworths, London, pp. 174–232.
VanHook, A. (1961) Historical review, in Crystallization Theory and Practice. Reinhold Publishing Corporation, New York, pp. 1–44.
Shankland, K. and David, W. I. F. (2002) Global optimization strategies, in Structure Determination from Powder Diffraction Data (David, W. I. F., Shankland, K., McCusker, L., and Baerlocher, Ch. eds.), Oxford University Presss, Oxford, pp. 252–285.
Harborne, J. B. (1984) Methods of plant analysis, in Phytochemical Methods, 2 ed., Chapman and Hall, London, pp. 1–36.
Harborne, J. B. (1984) Nitrogen Compounds, in Phytochemical Methods, 2 ed., Chapman and Hall, London, pp. 176–221.
Harborne, J. B. (1984) Sugars and their derivatives, in Phytochemical Methods, 2 ed., Chapman and Hall, London, pp. 222–242.
Harborne, J. B. (1973) Nitrogen compounds, in Phytochemical Methods, 1 ed., Chapman and Hall, London, pp. 166–211.
Harborne, J. B. (1984) The terpenoids, in Phytochemical methods, 2 ed., Chapman and Hall, London, pp. 100–141.
Trease, G. E. and Evans, W. C. (1996) Phenols and phenolic glycosides, in Pharmacognosy, 14 ed., W B Saunders Company Ltd., London, pp. 218–254.
Harborne, J. B. (1984) Organic acids, lipids and related compounds, in Phytochemical Methods, 2 ed., Chapman and Hall, London, pp. 142–175.
Trease, G. E. and Evans, W. C. (1996) Vitamins and hormones, in Pharmacognosy, 14 ed., W B Saunders Company Ltd., London, pp. 441–450.
Trease, G. E. and Evans, W. C. (1996) Hydrocarbons and derivatives, in Pharmacognosy, 14 ed., W B Saunders Company Ltd., London, pp. 172–190.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2006 Humana Press Inc., Totowa,NJ
About this protocol
Cite this protocol
Florence, A.J., Shankland, N., Johnston, A. (2006). Crystallization in Final Stages of Purification. In: Sarker, S.D., Latif, Z., Gray, A.I. (eds) Natural Products Isolation. Methods in Biotechnology, vol 20. Humana Press. https://doi.org/10.1385/1-59259-955-9:275
Download citation
DOI: https://doi.org/10.1385/1-59259-955-9:275
Publisher Name: Humana Press
Print ISBN: 978-1-58829-447-0
Online ISBN: 978-1-59259-955-4
eBook Packages: Springer Protocols