Cristalización

Small Molecule Crystallization
Jessica K. Liang
Department of Chemical Engineering Illinois Institute of Technology ACS Summer School July 2003 Chicago IL

Overview
Ø Basic Crystal Science Ø Crystallization Process Ø Our Research Projects Ø Lab Tour

What is a Crystal?

New York Crystal

London Amorphous

Definition of Crystal
Ø Solid with short and long range order with atoms ormolecules in a fixed lattice arrangement Ø The distinction between a crystal and an amorphous solid is that between order and disorder over large distances Ø Internal structure of crystals accessible by x-ray diffraction analysis

Crystal Structure

Unit cell parameters: a, b, c, α, β, γ

Seven Crystal Systems

Space Groups
Ø 230 space groups Ø For organic molecules, statistics showsthat 95% of all compounds crystallize out in these 16 space groups
• P21/c monoclinic • P21 monoclinic • P21/m monoclinic • P2/c monoclinic • C2/c monoclinic • C2/m monoclinic • Cc monoclinic • C2 monoclinic • P-1 triclinic • P1 triclinic • P212121 orthorhombic • Pbca orthorhombic • Pnma orthorhombic • Pna21 orthorhombic • Pbcn orthorhombic • Pca21 orthorhombic • P21212 orthorhombic

X-RayDiffraction
Structure Determination Ø Need good quality single crystal Send to Crystallographer.
Ø They determine lattice type, parameters i.e. a, b, c, α, β, γ atom positions and space group Ø Space groups relate crystal symmetry on an atomic scale to possible arrangement of atom which possess that symmetry. Ø Given systems and space group you can calculate all possible arrangement of atoms whichmeet this symmetry.

Types of Crystals
Ø Ionic – Charged ions held in place on lattice by electrostatic forces (NaCl) Ø Covalent – Atoms connected by framework of covalent bonds (Diamond) Ø Molecular Crystals – Usually organic, composed of discrete molecules held together by weak attractive forces (Urea) Ø Metallic Crystals – Ordered arrays of identical cations (Copper)

Morphology and HabitØ Crystal morphology is defined as the general

appearance of crystals described by the Miller indices of the faces that show and give the crystals their characteristic shape Ø Crystal habit means the general shape of a crystal as given by the relative length of the various major axes. Ø Both morphology and habit depend on growth conditions and can vary under different process conditions.Morphology and Habit

Same morphological form but different habit

Different morphological form but same habit

Crystal Size Distribution
Ø CSD: the most widely applied quality test of a crystalline product Ø Many industrial processes demand a narrow range of particle size as this results in good filtering, drying and freeflow ability

Sizing Method

On-lined sizing

Polymorphism
ØThe phenomenon of a

chemical species having more than one possible crystal form e.g. Carbon (graphite: top and pencil and diamond: bottom) whilst remaining chemically identical Ø Different forms maybe significantly different in terms of both their structures and physical & chemical properties

5-Methyl-2-[(2-nitrophenyl)amino]-3-thiophenecarbonitrile

“ROY”

6 Polymorph Forms
Reference:Yu, L.; Stephenson, G. A.; Mitchell, C. A.; Bunnell, C. A.; Snorek, S. V.; Bowyer, J. J.; Borchardt, T. B.; Stowell, J. G; Byrn, S. R. J. Am. Chem. Soc. 2000, 122, 585.

McCrone’s Law
‘Every compound has different polymorphic forms, and that, in general,the number of forms known for a given compound is proportional to the time and money spent in research on that compound.’
McCrone, W.C.Polymorphism in Physics and Chemistry of the Organic Solid State, Ed. by Fox D, Labes MM, Weissberger A1965, Vol. II, pp. 726-767, Wiley Interscience New York.

Types of Polymorphism
Packing Polymorphism
Ø Packing and bonding arrangement of the structure in its different forms are significantly different

Conformational Polymorphism
Ø The existence of different conformers of the same molecule...