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Hydrothermal crystallization of organic compounds

Authors Shek, Lai Yung
Issue Date 2004
Summary The background of our studies in hydrothermal crystallization of organic compounds and in particular the ideas of organic crystal-engineering based on supramolecular principles is presented in Chapter 1. Chapter 2-5 then describe the application of hydrothermal conditions to the preparation of organic co-crystals of aromatic acids and bases. In general when comparing hydrothermal and ambient crystallization for these systems, hydrothermal conditions appear advantageous in producing higher yield, higher phase purity products, readily isolated and frequently with enhanced crystal size up to several mm in dimension. They also appear to more readily allow the thermodynamic control of co-crystal stoichiometry. This topic is commenced in Chapter 2, which describes the synthesis and structures of eleven new co-crystals of bipyridines with isopththalic and terephthalic acids. Through appropriate variations of conditions co-crystal of 1:1 or 1:2 stoichiometry can be formed for the isophthalic system. In the 1:1 adducts linear zig-zag chains are found though they can occur with different polymorphic forms, as found for each of the 1:1 co-crystals [Bipy] [IPA-H2] and [BPEA] [IPA-H2]. The 1:2 stoichiometry compounds involve association of the isophthalic acids with the pyridines through O-H...N hydrogen bonds and themselves through O-H...O H-bonding. By contrast in the terephthalic acid system the strong tendency to simple linear chain formation through O-H...N hydrogen bonding of the carboxylic acid and pyridines means that only 1:1 co-crystals are formed. Chapter 3 describes the related chemistry of the co-crystals formed between bipyridines (bipy), (BPEA) and (BPEE) and phthalic acid (PHA-H2). Once again crystal of 1:1 and 1:2 stoichiometry may be formed. The 1:1 compounds are neutral molecular adducts with O-H...N hydrogen bonding, and several polymorphic forms are found, for bipy, BPEA and BPEE. The 1:2 compounds are different in having proton transfer have bipyridinium dications and the hydrogen-phthalate mono-anions [Bipy-H2][PHA-H]2. Whist the phthalate anion is typically simple planar entity with intramolecular O-H...O hydrogen bond, one polymorph of [BPEA-H2] [PHA-H]2 has chains of hydrogen phthalate ions, which form supramolecular cavities for the BPEA-H2 ions. Chapter 4 describes the co-crystals of various bipyridines with hemi-mellitic acid [HEM-H3]. Again different stoichiometries co-crystals are found along with polymorphs. The hem-mellitates have strong tendency to segregate hydrophilic and hydrophobic segments. This has led to novel structures in which N-H...N bonded chains of monopyridinium [BPEE-H] ions have formed to separate out from the hemi-mellitate layers. Chapter 5 discusses the co-crystals of bipyridines with benzene-l,3,5-tricarboxylic acid, trimesic acid (TMA-H3) and compares with those from 3,5-pyridinedicarboxylic acid (PDA). These lead to a number of open 'chick-wire' hydrogen bond networks, with varying stoichiometry. In the bipy-PDA-H2 system three different stoichiometries are found along with 'molecular-slip' type poly-polymrphic forms. Finally in Chapter 6 we explore some other themes of organic hydrothermal crystallization through the results of a number of case studies, in which the technique can be applied to grow large organic crystals and examine issues of natural product and drug identification, stability and chiral resolution. The artemisinin familiy of anti-malarial compounds, hydrothermal crystallization of artemisinin itself can lead to large bar of 2mm dimension. In general though these organic peroxides are unstable in solution at temperature above 110°C and sub-hydrothermal condition 70-80°C have used to explore crystallization of compounds, high temperature polymorphs and examine the hydrolytic decomposition of some of these compounds. Other cases studies involve the case of optimal crystal growth and stoichiometric control found in the 4,4'-bipyridine-squaric acid system, the co-crystallization of a chiral salt of 1-tetrahydropalmatine through use of D-tartaric acid. Hydrothermal crystal growth up to 5mm allowed study by neutron diffraction of the single well N-H-O and N-D-O hydrogen bonds found in 3,5-pyridinedicarboxylic acid (PDA-H2 or dinicotinic acid) and its deuterated analogue which was crystallized hydrothermally using deuterium oxide as solvent.
Note Thesis (Ph.D.)--Hong Kong University of Science and Technology, 2004
Language English
Format Thesis
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