Thesis (Ph. D.)--University of Texas at Austin, 1998. / Vita. Includes bibliographical references (leaves 140-149). Available also in a digital version from Dissertation Abstracts.

Thesis (MTech (Chemistry))--Cape Peninsula University of Technology, 2012. / Chirality is very important to the pharmaceutical industry as enantiomers have the same macroproperties except for their optical and pharmacological activity. Industrial research has thus focused to find the most effective resolution technique. However, our aim was to obtain more information regarding the discrimination process. In this project the structures of the hydrates of diquininium L-malate, (2QUIN+)(L-MA2-)·2H20 and the di-quininium O-malate, (2QUIN+)(D-MA2-)·2H20 have been investigated. (-)-Quinine (QUIN) did not show selectivity between the 0 and L malic acid and the structure of (2QUIN+)(DL-MA2-)·2H20 was obtained. Effect of solvents was demonstrated in the study and the structure of (QUIN+)(D-MA-)·H20) was reported. The relationship between C-O bonds of the carboxylate and carboxylic moieties and L'lpKa was explored in salt and co-crystal formation. Kinetics of absorption was conducted for the reaction of (+)-deoxycholic acid (DCA) with npropylamine and DCA with racemic sec-butylamine. The rate constants of the reactions were determined. Kinetics of desolvation was performed on the powder samples of mixtures of DCA and sec-butylamine and DCA with di-n-butylamine. Non-isothermal methods were used where a series of TG analyses was carried out at different heating rates (2, 4, 10, 32 K rnin'). The structures of DCA with n-propylamine and di-n-butylamine were elucidated. The selectivity of DCA was investigated. The host compound was found to be able to successfully resolve racemic sec-butylamine (2-BUAM) and 2-amino-3-methylbutane (MeBUAM). The structures of DCA with enantiomers of these guests are reported in the study. The structures of RBUAM and S-BUAM were solved in different space groups while R-MeBUAM and S-MeBUAM crystallized in the same space group.

The work presented in this thesis is aimed to design efficient reactive crystallization operations that could potentially be implemented in the manufacture of enantiomerically pure compounds and β-lactam antibiotics. Multiple aspects of solution thermodynamics, reaction engineering and crystallization from complex solutions are involved and will be discussed in detail through the following chapters. The first piece of this work utilizes reactive crystallization for the manufacture of enantiomerically pure amino acids. Chemo-enzymatic stereoiversion reactions are used to enrich saturated or supersaturated solutions to favor the selection of a desired enantiomer. L-Methionine and L-Phenylalanine were resolve successfully from racemic mixtures by cyclic stereoinversion. r D-amino acids were oxidized by D-amino acid oxidase (D-AAO) and the resulting ketoacid was subsequently reduced by ammonia borane producing a racemic-mixture After the necessary enantiomeric enrichment was reached, system conditions were changed to induce supersaturation and promote crystal formation. In each case crystals with chemical and enantiomeric purities greater than 99% wt. were recovered. experimental information about reaction and crystallization kinetics was used to developed models. Such models were used to design model-based optimizations in which the productivity of the operation was enhanced by selecting an optimal temperature profile. The second example is a reactive crystallization towards the manufacture of β-lactam antibiotics. One of the major drawbacks of the utilization of enzymes towards the manufacture of β-lactam antibiotics is the fact that the same enzyme that catalyzes the synthesis of the antibiotic also catalyzes its hydrolysis and thus, its degradation. The reaction scheme is a kinetically controlled synthesis in which the desired product is an intermediate within the network. Hence, the focus of this work is to design an efficient reactive crystallization in which the product is crystallized before it is consumed by hydrolysis. In order to accomplish this goal we have study solution equilibria, reaction kinetics, and crystallization kinetics. Even though crystallization kinetics of ampicillin has been previously reported; the reported models are not applicable to a reactive crystallization scheme for a variety of reasons. In this work, we have developed a robust model that can be applied to multiple crystallization protocols that are consistent with the conditions at which the enzymatic reaction can be performed. Finally, a reactive-crystallization scheme in which ampicillin was successfully recovered from solution was developed. In this work, crystal seeds were used to promote crystallization of the desired product from the complex media. The results indicated that is possible to perform the reaction and crystallization in parallel, and still recover crystals with high purity. This work is the first example in which ampicillin was produced and recovered with high purity in a single stage. Previous work on reaction crystallization of antibiotics reported ampicillin crystallization; however, this was accompanied by precipitation of by-products which greatly reduces the applicability of the operation as product purification is required after the reaction.

by Qian Wang. / Thesis (Ph.D.)--Chinese University of Hong Kong, 1992. / Includes bibliographical references (leaves 107-111). / Acknowledgements --- p.i / Contents --- p.ii / Abstract --- p.iv / Chapter I. --- Introduction --- p.1 / Chapter II. --- Results and Discussion --- p.23 / Chapter II-1. --- "Stereoselective Synthesis of Chiral Liquid Crystalline Compounds Containing a 1,4-Disubstituted Cyclohexene Ring" --- p.23 / Chapter II-1-1. --- "Synthesis of (S)-(-)- and (R)-(+)-4'-(4""-Cyanobiphenyl) 4-Pentyl-3-cyclohexene-1-carboxylate (1 and 3) and (S)-(-)-4'-(4""-Octoxybiphenyl) 4-Pentyl-3-cyclohexene-1-carboxylate (2)" --- p.23 / Chapter II-1-2. --- "Synthesis of (S)-(-)-4'-(4""-Cyanobiphenyl) 4-Butoxymethyl-3-cyclohexene-1-carboxylate (4)" --- p.35 / Chapter II-1-3. --- "Synthesis of (S)-(-)- and (R)-(+)-4'-(4""-Heptoxybiphenyl) 4-(2-Propenyl)-1-cyclohexene-1-carboxylate (5 and 7) and (S)-(-)- and (R)-(+)-4'-(4""-Octoxybiphenyl) 4-(2-Propenyl)-1-cyclohexene-1-carboxylate (6 and 8)" --- p.37 / Chapter II-2. --- "Synthesis of Chiral Liquid Crystalline Compound Containing a trans-2,5-Disusbstituted Cyclohexanone Ring´ؤ(1S,4S)-4'-(4""-Heptoxybiphenyl) 4-Penyl-3-cyclohexanone-1-carboxylate (9)" --- p.42 / Chapter II-3. --- "Determination of Enantiomeric Purities of (S)-(-)- and (R)-(+)-Perillalcohols (17 and 28), (S)-(-)- and (R)-(+)-1-Pentyl-4-hydroxymethyl-l-cyclohexenes(35 and 36), and (2S,5S)-2-Pentyl-5-hydroxymethyl-l-cyclohexanone (64)" --- p.58 / Chapter II-3-1. --- Determination of Enantiomeric Purities of (S)-(-)- and (R)-(+)-Perillalcohols (17 and 28) --- p.58 / Chapter II-3-2. --- Determination of Enantiomeric Purities of (S)-(-)- and (R)-(+)-1-Pentyl-4-hydroxymethyl-1-cyclohexenes (35 and36) --- p.64 / Chapter II-3-3. --- "Determination of Enantiomeric Purity of (2S,5S)-2-Pentyl-5-hydroxymethyl-1 -cyclohexanone (64)." --- p.67 / Chapter II-4. --- "Mesomorphic Phases and Transition Temperatures of Chiral Liquid Crystalline Compounds 2, 3, 5, 6, 7, 8 and 9" --- p.72 / Chapter III. --- Conclusion --- p.77 / Chapter IV. --- Experimental --- p.78 / Chapter V. --- References --- p.107 / List of Spectra --- p.112 / Spectra --- p.116

Imidazolinones represent a new class of herbicides with low mammalian toxicity that can be used at low application rates, either pre- or post-emergence for the control of a wide range of weeds in broadleaf and cereal crops, and non-crop situations. All imidazolinone herbicides are chiral, containing two enantiomers that derive from the chiral centre of the imidazolinone ring. The inhibitory activity of the R(+) enantiomer is nearly eight times greater than that of the S(-) enantiomer. The use of imidazolinone herbicides has increased in recent years in Australia owing to increased popularity of pulses and the introduction of imidazolinone-tolerant canola and wheat. Concerns have been raised about the potential carry over damage to the subsequent crops grown in rotation with legumes and herbicide tolerant crops. Furthermore, the presence of alkaline soils in some regions of Australia may lead to the repellence of imidazolinone herbicides, which are chiefly present in anionic form at high pH values. Thus leaching and potential contamination of ground water may occurr when these herbicides are applied on alkaline soils in certain agroclimatic zones. There is some information in the literature on the degradation, sorption and leaching behaviour of these herbicides in the environment. However, there is little information about the behaviour of these herbicides in alkaline soils found in some areas of Australia. Until now there has been no investigation of enantioselectivity in the degradation of imidazolinone herbicides in soils. Therefore, this study was undertaken to determine the behaviour of three imidazolinone herbicides in solution and Australian soils including enantioselectivity in the degradation of these herbicides in Australian soils. Analytical method for these herbicides needed to be developed/improved to cater for specific experimental conditions for this study, namely the matrices containing higher levels of organic carbon and to analyse the two enantiomers of these herbicides. The extraction of imazapyr, imazethapyr and imazaquin was investigated using solid-phase extraction (SPE) procedure. The evaluation of different aqueous solutions (0.1 KCl, 0.5 M NaOH, 0.01M NaOH and 0.5M MeOH:NaOH, (80:20)) showed that the recovery of all three herbicides was greater than 70%. However, the highest level of herbicide recovery was obtained with 0.5M NaOH as the extraction solution. Evaluation of different solid phase extraction cartridges showed that PPL cartridge is most appropriate for the isolation and subsequent quantification of these herbicides in water and humic-amended solutions when used at pH 2. When used with soil extracts, SPE cartridges C[subscript]18 + SCX allowed removal of co-extracting substances, resulting in high levels of herbicide recovery and accurate quantification with HPLC. These improved protocols were used in subsequent studies. The abiotic degradation of the imidazolinone herbicides imazapyr, imazethapyr and imazaquin was investigated under controlled laboratory conditions. Hydrolysis, where it occurred, and photodegradation both followed first order kinetics for all herbicides. There was no hydrolysis of any of the herbicides in buffer solutions at pH 3 or pH 7; however, slow hydrolysis occurred at pH 9. Degradation of the herbicides in the light was considerably more rapid than in the dark with half lives for the three herbicides of 1.8, 9.8 and 9.1 days for imazaquin, imazethapyr and imazapyr, respectively. The presence of humic acids in the solution reduced the rate of photodegradation for all three herbicides, with higher concentrations of humic acids generally having greater effect. The enantioselectivity of photodegradation was investigated using imazaquin, with photodegradation occurring at the same rate for both enantiomers. Abiotic degradation of imidazolinone herbicides on the soil surface only occurred in the presence of light. The rate of degradation for all three herbicides on the soil surface was slower than in solution, with half-lives of 15.3, 24.6 and 30.9 days for imazaquin, imazethapyr and imazapyr, respectively. Sterilizing the soil significantly (p < 0.05) decreased the degradation rate of both enantiomers of imidazolinone herbicides, with 81.5 to 89.5% of each enantiomer of the two herbicides remaining unchanged. However, in non-sterilized soils, the degradation of imazapyr and imazethapyr showed enantioselectivity with faster degradation of R(+) enantiomer compared with S(-) enantiomer. There were also some differences in enantioselectivity between different soils, which could be related to variation in microbial populations and enzymes present in different soils. Soil pH had a significant effect on enantioselectivity, which could be due to the effect of this soil property on herbicide sorption and ease of its availability for microbial degradation. This aspect however needs further investigations. Results from studies on soils receiving organic amendment (lupin residue) showed that degradation of the S(-) and R(+) enantiomers of imazethapyr and imazaquin followed firstorder reaction with half-life values of 45.9 to 105 days in non-sterilized soils for S(-) and R(+) enantiomers, respectively. Irrespective of the organic amendment, the degradation rate of the S(-) and R(+) enantiomers of the two herbicides was greater in the Roseworthy (pH 8.2) soil compared with the Clare soil (pH 5.2). Addition of lupin residue as organic amendment (2% w/w) increased degradation rates of both the S(-) and R(+) enantiomers of imazethapyr and imazaquin and significantly (p < 0.05) decreased their half-lives in the Clare soil. However, this amendment produced no significant change in degradation of enantiomers of either of the two herbicides in Roseworthy soil. The enantiomer fraction (EF) values of both herbicides increased over time, which suggested selective degradation of one enantiomer in preference to the other depending on the type of soil and amendment treatment. In the Clare soil, organic amendment increased the EF value at the end of incubation period from 0.61 to 0.76 for imazethapyr and from 0.56 to 0.66 for imazaquin, indicating enantioselective degradation of these herbicides. There was no significant increase in EF values for both herbicides in Roseworthy soil as the result of organic amendment. In conclusion, photodegradation of imidazolinone herbicides was found to have a major impact on the behaviour of these herbicides in aqueous and soil matrices. The degradation of imidazolinone herbicides in the soil was enantioselective, however, the enantioselectivity tended to be compound-specific and was related to soil types. The findings of this study are expected to be useful for the manufacturers to decrease the amount of chemical load in the environment. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1331166 / Thesis (Ph.D.) -- University of Adelaide, School of Agriculture, Food and Wine, 2008

Thesis (Ph. D.)--University of Texas at Austin, 1999. / Vita. Includes bibliographical references (leaves 140-153). Available also in a digital version from Dissertation Abstracts.

No description available.

Thesis (Ph.D.) -- University of Adelaide, School of Agriculture, Food and Wine, Discipline of Plant and Food Science, 2008. / Includes bibliography (leaves 151-177) Also available in print form.

Thesis (Ph.D.)--Michigan State University. Dept of Chemistry, 2006. / Title from PDF t.p. (viewed on June 19, 2009) Includes bibliographical references. Also issued in print.

Thesis (doctoral)--Lund University, 1997. / Added t.p. with thesis statement inserted. Includes bibliographical references.