DOCSLIB.ORG

Bio-Based Solvents for Organic Synthesis

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Bio-Based Solvents for Organic Synthesis Bio-Based Solvents for Organic Synthesis James Richard Sherwood Submitted for the degree of Doctor of Philosophy University of York Department of Chemistry July 2013 2 Abstract Scrutiny over solvent selection in the chemical industry has risen in recent decades, popularising research into neoteric solvent systems such as ionic liquids and supercritical fluids. More recently bio-based solvent products have been considered as replacements for conventional petroleum derived solvents. Because they bear a close resemblance to existing solvent products, bio-based solvents can be readily absorbed into the fine chemical industries. This work develops a methodology for identifying reactions of concern with respect to current solvent selection practice, and then implementing a high performance bio-based solvent substitute. In this thesis, kinetic studies of heteroatom alkylation, amidation, and esterification are documented, and the solvent effect dictating the rate of each reaction ascertained. With the ideal properties for the solvent known, bio-based solvent candidates were screened for suitability in each case study. This process, which employs computational tools, was also applied to model the productivity of the Biginelli reaction as a representative multi-component heterocycle synthesis. A strong case is made for limonene and p-cymene as bio-based solvents for all but heteroatom alkylation from the case studies listed above. Alkylations with nitrogen nucleophiles are instead suited to high polarity solvents, and to this end some bio-based amides were investigated. 3 4 Contents List of figures 9 List of schemes 17 List of tables 21 Acknowledgements 27 Declaration 29 1 Introduction: A critical analysis of green and renewable solvents 33 1.1 Modern solvent use 34 1.2 Properties of solvents 37 1.3 Solvent selection 51 1.4 Analysis of bio-based solvents 63 2 Nucleophilic substitution 77 2.1 Solvents and nucleophilic substitution 77 2.2 Nucleophilic substitution results and discussion 81 2.3 Heteroatom alkylation summary 111 3 Amidation 117 3.1 Solvents and amidation 117 3.2 Amidation results and discussion 127 3.3 Amidation summary 153 4 Uncatalysed esterification 157 4.1 Solvents and esterification 157 4.2 Uncatalysed esterification results and discussion 161 4.3 Esterification summary 175 5 5 Catalysed carbonyl addition 179 5.1 Bio-based acid catalysts for organic chemistry 179 5.2 Combined solvent and catalytic effects in carbonyl additions 191 5.3 Catalysed carbonyl addition summary 204 6 Heterocycle synthesis: The Biginelli reaction 209 6.1 Introduction to Pietro Biginelli and his reaction 209 6.2 Standard Biginelli reaction solvent effects 214 6.3 Modified Biginelli reaction solvent effects 237 6.4 Biginelli reaction summary 240 7 Conclusion 245 7.1 Case study recapitulation 245 7.2 The future of bio-based solvents 248 8 Appendices 255 8.1 Experimental procedures 255 8.2 Supplementary data 261 Abbreviations 285 References 295 6 7 8 List of figures Figure 1.1 Materials (by mass) required for the manufacture of a typical pharmaceutical product. Figure 1.2 A comparison between reaction class frequency in process chemistry and manufacturing plant chemistry within the pharmaceutical industry. Figure 1.3 An energy profile of 4-nitroaniline dissolving in acetic acid. Figure 1.4 A comparison between relative permittivity and the Hildebrand solubility parameter. Figure 1.5 Three dimensional Hansen plot based on the solubility of urea. Figure 1.6 The solvent effect influencing the light absorbance of Reichardt’s betaine dye. Figure 1.7 The solvent polarity scale derived from Reichardt’s dye. Figure 1.8 The solvatochromism of N,N-diethyl-4-nitroaniline. Figure 1.9 The UV-vis. spectrum of N,N-diethyl-4-nitroaniline in cyclohexane, 2-MeTHF, and DMSO. Figure 1.10 A comparison between aniline dye absorbance maxima in different solvents. Figure 1.11 Aprotic solvent polarity map. Figure 1.12 Protic solvent polarity map. Figure 1.13 A visual representation of the algorithmic solvent selection process. Figure 1.14 Rule D of the solvent selection algorithm. Figure 1.15 Rule C (R2a) of the revised solvent selection algorithm when the solvent is opted to be recycled. Figure 1.16 An arbitrary polarity map with rule G assignments from the revised solvent selection algorithm. Figure 1.17 A hypothetical comparison between methods for identifying the permissible toxicity limits of solvents when the user defined limit is log(LD50) = 3.5. 9 Figure 1.18 A linear free energy diagram showing the acidity of benzoic acids in different solvents. Figure 1.19 The rate of a Fischer esterification correlated to solvent polarity. Figure 1.20 Aprotic bio-based solvent polarity map. Figure 1.21 Protic bio-based solvent polarity map. Figure 2.1 The natural logarithms of rate constants (relative to methanol) for the Menschutkin reaction. Figure 2.2 The progression of the model Menschutkin reaction in DMSO as observed by 1H-NMR spectroscopy. Figure 2.3 The conversion to 1-decyl-2,3-dimethylimidazolium bromide with the Menschutkin reaction in DMSO and ethanol as determined by 1H-NMR spectroscopy. Figure 2.4 Integrated rate equations of Menschutkin reactions in DMSO and ethanol. Figure 2.5 The polarity of the model Menschutkin reaction solvent set. Figure 2.6 The SUS-HAS-ECO classifications of the model Menschutkin reaction solvent set. Figure 2.7 The LSER describing the rate constant of the model Menschutkin reaction as a function of solvent dipolarity only. Figure 2.8 A comparison between experimental and predicted SN2 ln(k) values based on a LSER incorporating both π* and α Figure 2.9 Predicted ln(k) values from the LSER featuring the ε modification to α compared to experimental Menschutkin reaction data. Figure 2.10 A systematic error check of experimental rate constants for the model Menschutkin reaction. Figure 2.11 A demonstration of the absence of a correlation between Reichardt’s parameter and ln(k) of the model Menschutkin reaction. Figure 2.12 The relationship between relative permittivity and experimental values of ln(k) of the model Menschutkin reaction. Figure 2.13 An arbitrary free energy diagram indicating Menschutkin reaction solvent effects in DMSO relative to chloroform and ethanol. 10 Figure 2.14 Menschutkin reaction solvent selection algorithm screenshot, step 1: Reaction components. Figure 2.15 Menschutkin reaction solvent selection algorithm screenshot, step 2: Solvent class inclusion. Figure 2.16 Menschutkin reaction solvent selection algorithm screenshot, step 3: Parameter input. Figure 2.17 Menschutkin reaction solvent selection algorithm screenshot: Polarity matching diagram for estimating the solubility of 1,2-dimethylimidizole. Figure 2.18 Menschutkin reaction solvent selection algorithm screenshot, step 4: Scoring system. Figure 2.19 Menschutkin reaction solvent selection algorithm screenshot, step 5: Solvent effects. Figure 2.20 Menschutkin reaction solvent selection algorithm screenshot, step 6: Solvent selection guide. Figure 2.21 Menschutkin reaction solvent selection algorithm screenshot, step 7: Results preview. Figure 2.22 Bio-based amide solvent yields. Figure 2.23 The polarity of highly dipolar aprotic solvents including bio-based amides. Figure 2.24 The performance of bio-based amide solvents and sulpholane in the Menschutkin reaction. Figure 3.1 A reproduction and simplification of the Pfizer reagent selection Venn diagram for amide coupling protocols. Figure 3.2 An example of a 1H-NMR spectrum showing the partially complete model amidation in toluene. Figure 3.3 Amidation reaction order determination in toluene. Figure 3.4 A polarity map of solvents included in the initial screening of the model amidation reaction. Figure 3.5 The environmental, health and safety of amidation solvents. Figure 3.6 The LSER correlating the rate of the model amidation reaction with the hydrogen bond accepting ability of the solvent. 11 Figure 3.7 A multi-solvent Eyring relationship for amidation including a predicted crossover point of reaction rates at an iso-kinetic temperature. Figure 3.8 The correlation between the enthalpy of activation and solvent hydrogen bond accepting ability (β). Figure 3.9 The correlation between the entropy of activation and solvent hydrogen bond accepting ability (β). Figure 3.10 The relationship between the activation parameters dictating the kinetics of the model amidation. Figure 3.11 The generalised variable enthalpy of amidation illustrated in toluene and DMSO. Figure 3.12 The toluene-DMSO binary solvent effect on the rate of amidation. Figure 3.13 Amidation reaction solvent selection algorithm screenshot, step 3: Parameter input. Figure 3.14 Amidation reaction solvent selection algorithm screenshot, step 6: Solvent selection guide. Figure 3.15 A LSER indicating the performance of limonene and p-cymene in amidation reactions. Figure 3.16 Estimated versus predicted ln(k) values of amidation. Figure 3.17 Systematic error check in the amidation rate constants. Figure 3.18 Isolated yields of N-benzyl-4-phenylbutanamide from different solvents. Figure 3.19 Associated metrics of amidation reactions between 4-phenylbutanoic acid and benzylamine unless otherwise stated. Figure 3.20 The comparison of PMI in different amidations. Figure 4.1 The manipulation of a fluorous multiphasic system to enhance esterification yields. Figure 4.2 A 1H-NMR spectrum of the uncatalysed model esterification occurring in chloroform. Figure 4.3 Polarity map of solvents used in the initial uncatalysed model esterification solvent set. Figure
Load more

Recommended publications
  • Development and Validation of Liquid Chromatography-Based Methods to Assess the Lipophilicity of Cytotoxic Platinum(IV) Complexes
    Article Development and Validation of Liquid Chromatography-Based Methods to Assess the Lipophilicity of Cytotoxic Platinum(IV) Complexes Matthias H. M. Klose 1,2, Sarah Theiner 3, Hristo P. Varbanov 1,4, Doris Hoefer 1, Verena Pichler 1,5, Markus Galanski 1, Samuel M. Meier-Menches 2,3,* and Bernhard K. Keppler 1,2,* 1 Institute of Inorganic Chemistry, University of Vienna, 1090 Vienna, Austria; [email protected] (M.H.M.K.); [email protected] (D.H.); [email protected] (M.G.) 2 Research Cluster ‘Translational Cancer Therapy Research’, University of Vienna, 1090 Vienna, Austria 3 Department of Analytical Chemistry, University of Vienna, 1090 Vienna, Austria; [email protected] 4 Institute of Chemistry—Inorganic Chemistry, University of Graz, 8010 Graz, Austria; [email protected] (H.P.V.) 5 Division of Nuclear Medicine, Department of Biomedical Imaging and Image-Guided Therapy, Medical University of Vienna, 1090 Vienna, Austria; [email protected] (V.P.) * Correspondence: [email protected] (S.M.M.-M.); [email protected] (B.K.K.); Tel.: +43-1-4277-52373 (S.M.M.-M.); +43-1-4277-52602 (B.K.K.) Received: 2 October 2018; Accepted: 29 November 2018; Published: 4 December 2018 Abstract: Lipophilicity is a crucial parameter for drug discovery, usually determined by the logarithmic partition coefficient (Log P) between octanol and water. However, the available detection methods have restricted the widespread use of the partition coefficient in inorganic medicinal chemistry, and recent investigations have shifted towards chromatographic lipophilicity parameters, frequently without a conversion to derive Log P.
    [Show full text]
  • The Role of Hydrogen Bonding in Paracetamol–Solvent and Paracetamol–Hydrogel Matrix Interactions
    materials Article The Role of Hydrogen Bonding in Paracetamol–Solvent and Paracetamol–Hydrogel Matrix Interactions Marta Miotke-Wasilczyk *, Marek Józefowicz * , Justyna Strankowska and Jerzy Kwela Insitute of Experimental Physics, Faculty of Mathematics, Physics and Informatics, University of Gda´nsk, Wita Stwosza 57, 80-308 Gda´nsk,Poland; [email protected] (J.S.); [email protected] (J.K.) * Correspondence: [email protected] (M.M.-W.); [email protected] (M.J.) Abstract: The photophysical and photochemical properties of antipyretic drug – paracetamol (PAR) and its two analogs with different substituents (acetanilide (ACT) and N-ethylaniline (NEA)) in 14 solvents of different polarity were investigated by the use of steady–state spectroscopic technique and quantum–chemical calculations. As expected, the results show that the spectroscopic behavior of PAR, ACT, and NEA is highly dependent on the nature of the solute–solvent interactions (non- specific (dipole-dipole) and specific (hydrogen bonding)). To characterize these interactions, the multiparameter regression analysis proposed by Catalán was used. In order to obtain a deeper insight into the electronic and optical properties of the studied molecules, the difference of the dipole moments of a molecule in the ground and excited state were determined using the theory proposed by Lippert, Mataga, McRae, Bakhshiev, Bilot, and Kawski. Additionally, the influence of the solute polarizability on the determined dipole moments was discussed. The results of the solvatochromic studies were related to the observations of the release kinetics of PAR, ACT, and NEA from polyurethane hydrogels. The release kinetics was analyzed using the Korsmayer-Peppas and Hopfenberg models.
    [Show full text]
  • Lipophilicity (Logd7.4) of N-Aryl Benzo Hydroxamic Acids
    Global Journal of Pharmacy & Pharmaceutical Sciences ISSN: 2573-2250 Mini Review Glob J Pharmaceu Sci Volume 4 Issue 5 - february 2018 Copyright © All rights are reserved by Ajita Dixit DOI: 10.19080/GJPPS.2018.04.555648 Lipophilicity (LogD7.4) of N-Aryl Benzo Hydroxamic Acids Ajita Dixit* Pandit Ravishankar Shukla University, India Submission: July 24, 2017; Published: February 21, 2018 *Corresponding author: Ajita Dixit, Pandit Ravishankar Shukla University, India, Email: Abstract Hydroxamic acids are polyfunctional molecules which show a wide spectrum of biological and medicinal activities. Lipophilicity is known to be important for absorption, permeability and in vivo distribution of organic compound. Lipophilicity is also a major structural factor that influences the pharmacokinetic and pharmacodynamic behaviour of compound. Introduction homogeneously but rather, a gradient is formed that varies Lipophilicity is known to be important for absorption, with the composition and geometry of membrane [7]. The high permeability and in vivo distribution of organic compound degree of ordering of solutes in a lipid bi layer compared with a [1]. Since about one century, it is recognized as a meaningful parameter in Structure-activity relationship studies and with and partitioning. Never the less good correlation between the epoch making contributions of Hansch et al. [2] has become bulk liquid phase also significantly changes the thermodynamic the single most informative and successful physico-chemical membrane /buffer and octanol/water two phase’s systems has the partition coefficient of various lipophilic compounds in been observed [8]. property in medicinal chemistry. Lipophilicity is defined for a lipophilic environment.” Lipophilicity is determined Material and Methods “Lipophilicity represents the affinity of a molecule or a moiety valid only for a single chemical species) or as distribution experimentally as partition coefficients (written as logP and In the present investigation partition coefficient or n-Octanol and buffer as solvent.
    [Show full text]
  • Lipophilicity As a Central Component of Drug-Like Properties of Chalchones and Flavonoid Derivatives
    molecules Article Lipophilicity as a Central Component of Drug-Like Properties of Chalchones and Flavonoid Derivatives Teodora Constantinescu 1, Claudiu Nicolae Lungu 2,* and Ildiko Lung 3 1 Department of Chemistry, Faculty of Pharmacy, Iuliu Hatieganu University, 400012 Cluj-Napoca, Romania; [email protected] 2 Department of Chemistry, Faculty of Chemistry and Chemical Engineering, Babes-Bolyai University, 400028 Cluj-Napoca, Romania 3 National Institute for Research & Development of Isotopic and Molecular Technologies 67-103 Donath street, 400293 Cluj-Napoca, Romania; [email protected] * Correspondence: [email protected]; Tel.: +40-(0)-742-255-099 Received: 11 March 2019; Accepted: 10 April 2019; Published: 17 April 2019 Abstract: Lipophilcity is an important physico-chemical parameter that influences membrane transport and binding ability to action. Migration distance following complete elution of compounds was used to calculate different lipophilicity-related parameters. The aim of this study is to show that lipophilicity is a central component of thiazole chalcones and flavonoid derivatives regarding their drug-like properties. Experimental and computational methods were used. This study considers 44 previously synthesized compounds (thiazole chalcones, flavanones, flavones, 3-hydroxyflavones, and their acetylated derivatives). The concerned compounds have shown antitumoral hallmarks and antibacterial activity in vitro. The experimental method used to determine compounds’ lipophilicity was the reverse-phase thin layer chromatography (RP-TLC). Lipophilicity related 0 parameters—isocratic retention factor (RM), relative lipophily (RM ), slope (b), chromatographic hydrophobic index ('0), scores of principal components (PC1/RM)—were determined based on reverse-phase chromatography results. Keywords: lipophilicity; retention factor; chalcones; QSAR; chromatography; drug design 1. Introduction Lipophilicity is an important feature of molecules in pharmaceutical, biochemical, and medical chemistry fields.
    [Show full text]
  • Solvent Effect Modelling of Isocyanuric Products Synthesis by Chemometric Methods
    Journal of Automated Methods & Management in Chemistry Vol. 24, No. 4 (July–August 2002) pp. 111–119 Solvent e´ ect modelling of isocyanuric products synthesis by chemometric methods Jean-Louis Havet, Myriam Billiau-Loreau, electric constant) or by empirical parameters (Dimroth± Catherine Porte* and Alain Delacroix Reichardt constant, Kosower constant). These data can Laboratoire de Chimie Industrielle et Geè nie des Proceè deè s, Conservatoire National be considered as good but partial indicators of polarity. des Arts et Meè tiers, 2 rue Conteè , F-75003 Paris, France Furthermore, the accumulation of empirical values shows that none of these de® nitions is totally convenient. The Chemometric tools were used to generate the modelling of solvent use of several parameters that are not independent in N e¡ects on the -alkylation of an isocyanuric acid salt. The method multiparametric equations allows one to improve the proceeded from a central composite design applied on the Carlson quanti® cation of polarity, but it remains insuæ cient to solvent classi¢cation using principal components analysis. The have a general classi® cation of solvents [3]. selectivity of the reaction was studied from the production of di¡erent substituted isocyanuric derivatives. Response graphs were The most ambitious approach for a general classi® cation obtained for each compound and used to devise a strategy for of solvents uses multivariate statistical methods [4, 5]. solvent selection. The prediction models were validated and used to The compilation of the physicochemical constants of search for the best selectivity for the reaction system. The solvent solvents allows one to take diå erent properties simulta- most often selected as the best for the reaction is the N,N- neously into account.
    [Show full text]
  • Solvent Dependent Absorption and Fluorescence Ofaketocyanine Dye
    Indian Journal of Chemistry Vol. 34A, February 1995, pp. 94-101 Solvent dependent absorption and fluorescence of a ketocyanine dye in neat and binary mixed solvents Debashis Banerjee, Ashis Kumar Laha & Sanjib Bagchi" Department of Chemistry, Burdwan University, Burdwan 713 104, India Received 11 March 1994; revised and accepted 23 September 1994 The environmental effect on the ground and excited state properties of a ketocyanine dye has been studied by monitoring its absorption and fluorescence characteristics in various pure and bi- nary mixed solvents. The spectroscopic transition leading to the longest wavelength absorption or fluorescence has been found to involve considerable intramolecular charge transfer as evidenced by semiempirical MO calculations at the AMI level. Ground state complexation is indicated in protic solvents, aromatic hydrocarbons and cyclic ethers. The fluorescence maximum, E (F), shows a corre- lation with ET (30) scale of solvent polarity. A multiple linear correlation of E(F) with Kamlet-Taft parameter representing solvent dipolarity (n*) and hydrogen bonding ability (a and (3) suggests that apart from dipolar interactions specific solute-solvent interactions are important in determining flu- orescence maxima. Study of E (F) in mixed binary solvents points to a preferential solvation of the solute in the S 1 state. The polarity probes have found extensive applic- nine dye in pure and mixed binary solvents by ations during the last couple of years, especially monitoring its longest wavelength absorption and for the evaluation of various microenvironrnental fluorescence band. The dye chosen for the pre- properties 1-5. Although a large number of miCTOP- sent study is (1-1 ),(9-1)-di-l ,9-di-(2,3-dihydroindo- olarity reporters involving solvatochromic spectral lyl)- 4,6-dimethylene- nona-l,3,6,8-tetraene-5-one transition are known, e.g., 4-methoxycarbonylpyri- (Fig.
    [Show full text]
  • Acid Dissociation Constant - Wikipedia, the Free Encyclopedia Page 1
    Acid dissociation constant - Wikipedia, the free encyclopedia Page 1 Help us provide free content to the world by donating today ! Acid dissociation constant From Wikipedia, the free encyclopedia An acid dissociation constant (aka acidity constant, acid-ionization constant) is an equilibrium constant for the dissociation of an acid. It is denoted by Ka. For an equilibrium between a generic acid, HA, and − its conjugate base, A , The weak acid acetic acid donates a proton to water in an equilibrium reaction to give the acetate ion and − + HA A + H the hydronium ion. Key: Hydrogen is white, oxygen is red, carbon is gray. Lines are chemical bonds. K is defined, subject to certain conditions, as a where [HA], [A−] and [H+] are equilibrium concentrations of the reactants. The term acid dissociation constant is also used for pKa, which is equal to −log 10 Ka. The term pKb is used in relation to bases, though pKb has faded from modern use due to the easy relationship available between the strength of an acid and the strength of its conjugate base. Though discussions of this topic typically assume water as the solvent, particularly at introductory levels, the Brønsted–Lowry acid-base theory is versatile enough that acidic behavior can now be characterized even in non-aqueous solutions. The value of pK indicates the strength of an acid: the larger the value the weaker the acid. In aqueous a solution, simple acids are partially dissociated to an appreciable extent in in the pH range pK ± 2. The a actual extent of the dissociation can be calculated if the acid concentration and pH are known.
    [Show full text]
  • AP42 Chapter 9 Reference
    Background Report Reference AP-42 Section Number: 9.2.2 Background Chapter: 4 Reference Number: 22 Title: "Critical Review of Henry's Law Constants fro Pesticides" in Reviews of Environmental Contamination and Toxicology L.R. Suntio 1988 AP-42 Section 9! Reference Report Sect. 3c L2% Critical Review of Henry's Law Constants Reference for Pesticides L.R. Sunti0,'W.Y. Shiu,* D. Mackay,* J.N. Seiber,** and D. Glotfelty*** Contents ......... ........... ........... ............. IV. Data Analysis ........ ........... ......... I V. Discussion .......... ........... .......... 41 ............. so .......... ............ I. Introduction Pesticides play an important role in maintaining agricultural productivity, but they may also be causes of contamination of air, water, soil, and food, with possible adverse effects on human and animal health. The proper use of pesticide chemicals must be based on an understanding of the behavior of the chemicals as they interact with air, water, soil, and biota, react or degrade, and migrate. This behavior is strongly influenced by the chemicals' physical- chemical properties of solubility in water, vapor pressure or volatility, and tendency to sorb to organic and mineral matter in the soil. Reviews of such physical-chemical properties have been compiled by Kenaga (1980), Kenaga and Goring (1980), Briggs (1981), and Bowman and Sans (1983) for aqueous solubility, octanol-water partition coefficient, bio- accumulation, and soil sorption; Spencer and Cliath (1970, 1973. 1983). and Spencer (1976) for vapor pressure and volatilization from soil. In this chapter we compile and discuss data for Henry's Law constant H (which is the ratio of solute partial pressure in the air to the equilibrium water concentration and thus has units of Pa m3/mol) or the air-water partition 'Department ofchemical Engineering and Applied Chemistry.
    [Show full text]
  • Fundamental Insights Into the Dissolution and Precipitation of Cellulosic Biomass from Ionic Liquid Mixtures
    Fundamental Insights into the Dissolution and Precipitation of Cellulosic Biomass from Ionic Liquid Mixtures By David L. Minnick Submitted to the graduate degree program in Chemical and Petroleum Engineering and the Graduate Faculty of the University of Kansas in partial fulfillment of the requirements for the degree of Doctor of Philosophy. ________________________________ Chairperson: Aaron M. Scurto ________________________________ Bala Subramaniam ________________________________ Raghunath V. Chaudhari ________________________________ Laurence Weatherley ________________________________ Belinda Sturm Date Defended: July, 14th 2016 The Dissertation Committee for David L. Minnick certifies that this is the approved version of the following dissertation: Fundamental Insights into the Dissolution and Precipitation of Cellulosic Biomass from Ionic Liquid Mixtures ________________________________ Chairperson: Aaron M. Scurto Date approved: July, 22nd 2016 ii Abstract Ionic liquids (ILs) are a unique class of molecular salts that melt at temperatures below 100oC. The ionic functionality of ILs provide this class of molecules numerous advantages for applications in reactions, separations, and materials processing due to their molecular flexibility through cation/anion selection. Additionally, ionic liquids possess negligible vapor pressures and may lead to more sustainable or “green” processes by eliminating solvent-based air pollution. For these reasons ionic liquids are being targeted for implementation in a range of industrial processes as sustainable solvent technologies. The primary objective of this dissertation targets the application of ionic liquids to cellulosic biomass processing. For instance, chemical processing of biomass remains a challenge as the rigid inter- and intra- molecular hydrogen bonding network of cellulose renders it insoluble in nearly all aqueous and organic solvents. Alternatively, select ionic liquids (ILs) are capable of dissolving significant quantities.
    [Show full text]
  • The Effect of Lipophilicity on the Antibacterial Activity
    J. Serb. Chem. Soc. 73 (10) 967–978 (2008) UDC 577.15:547.53:615.281–188 JSCS–3778 Original scientific paper The effect of lipophilicity on the antibacterial activity of some 1-benzylbenzimidazole derivatives S. O. PODUNAVAC-KUZMANOVIĆ1*#, D. D. CVETKOVIĆ1 and D. J. BARNA2 1Faculty of Technology, Bulevar Cara Lazara 1, 21000 Novi Sad and 2Institute of Public Health, Zmaj Jovina 30, 24000 Subotica, Serbia (Received 27 February, revised 13 May 2008) Abstract: In the present paper, the antibacterial activity of some 1-benzylbenz- imidazole derivatives were evaluated against the Gram-negative bacteria Esche- richia coli. The minimum inhibitory concentration was determined for all the compounds. Quantitative structure–activity relationship (QSAR) was employed to study the effect of the lipophilicity parameters (log P) on the inhibitory ac- tivity. Log P values for the target compounds were experimentally determined by the “shake-flask” method and calculated by using eight different software products. Multiple linear regression was used to correlate the log P values and antibacterial activity of the studied benzimidazole derivatives. The results are dis- cussed based on statistical data. The most acceptable QSAR models for the pre- diction of the antibacterial activity of the investigated series of benzimidazoles were developed. High agreement between the experimental and predicted inhi- bitory values was obtained. The results of this study indicate that the lipophi- licity parameter has a significant effect on the antibacterial activity of this class of compounds, which simplifies the design of new biologically active molecules. Keywords: benzimidazole derivatives; lipophilicity; quantitative structure–acti- vity relationship; antibacterial; in vitro studies.
    [Show full text]
  • The Pennsylvania State University the Graduate School Department
    The Pennsylvania State University The Graduate School Department of Chemistry STUDY OF SOLVATION EFFECTS IN POLAR-PROTIC SOLVENTS USING COMPUTER SIMULATIONS A Thesis in Chemistry by Scot Richard Mente Submitted in Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy May 1999 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. UMI Number: 9938021 UMI Microform 9938021 Copyright 1999, by UMI Company. All rights reserved. This microform edition is protected against unauthorized copying under Title 17, United States Code. UMI 300 North Zeeb Road Ann Arbor, MI 48103 Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. We approve the thesis of Scot Richard Mente. Date of Signature Mark Maroncelli Professor of Chemistry Thesis Advisor Chair of Committee Professor of Vy/v Desjarlais Assistant Professor of Chemistry z/'+n 1 tong-Qing Associate Professor of Materials Science and Engineering f o si tin Peter C. Jurs( Professor of Chemistry Acting Head of the Department of Chemistry Reproduced with permission of the copyright owner. Further reproduction prohibited without permission. ABSTRACT Computational chemistry techniques are used to study various aspects of solvation and solvent effects in polar-protic systems. A variety of methods have been utilized, including Monte Carlo and molecular dynamics simulations, as well as semi-empirical and ab initio calculations. The first part of this thesis examines the solvent catalyzed proton transfer reaction in 7-Azaindole and 1 -Azacarbazole. In Chapter 2 classical Monte Carlo and molecular dynamics simulations are used to examine the structure and dynamics of solvation of aza- aromatic solutes in alcohol and water solvents in an effort to determine whether the existing interpretations of the solvent participation in these reactions are reasonable.
    [Show full text]
  • Photochemical Processes Induced by the Irradiation of 4-Hydroxybenzophenone in Cite This: Photochem
    Photochemical & Photobiological Sciences PAPER Photochemical processes induced by the irradiation of 4-hydroxybenzophenone in Cite this: Photochem. Photobiol. Sci., 2015, 14, 2087 different solvents† Francesco Barsotti,a Marcello Brigante,*b Mohamed Sarakha,b Valter Maurino,a Claudio Mineroa and Davide Vione*a,c The singlet and triplet excited states of 4-hydroxybenzophenone (4BPOH) undergo deprotonation in the presence of water to produce the anionic ground-state, causing fluorescence quenching and photoactiv- ity inhibition. The same process does not take place in an aprotic solvent such as acetonitrile. In aceto- nitrile, 4BPOH is fluorescent (interestingly, one of its fluorescence peaks overlaps with peak C of humic substances), it yields singlet oxygen upon irradiation and induces the triplet-sensitised transformation of phenol (with a rate constant of (6.6 ± 0.3) × 107 M−1 s−1 (μ ± σ) between phenol itself and a triplet 4BPOH). The 4BPOH shows an intermediate behaviour in a partially protic solvent such as 2-propanol, where some deprotonation of the excited states is observed. In acetonitrile/2-propanol mixtures (at least up to 50% of 2-propanol) there is also some evidence of alcohol oxidation by the 4BPOH triplet state, Received 25th May 2015, while the experimental data are silent concerning such a possibility in pure 2-propanol. Considering that Accepted 23rd September 2015 benzophenones are important components of chromophoric dissolved organic matter (CDOM) in surface DOI: 10.1039/c5pp00214a waters, the present findings could have significance for the photoactivity of the hydrophilic surface layers www.rsc.org/pps vs. the hydrophobic cores of CDOM. 5 Introduction T1, which triggers important triplet-sensitised processes.
    [Show full text]