DOCSLIB.ORG

Resolutions of Racemates by Crystallization Additives and Attrition

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Resolutions of Racemates by Crystallization Additives and Attrition Resolutions of Racemates by Crystallization Additives and Attrition Michel S. Leeman The cover picture shows backlit quartz form Tequisquiapan, Queretaro, Mexico, downloaded from: http://www.sxc.hu/photo/702163. This research project, named Ultimate Chiral Technology (UCT), was financially supported by Syncom B.V., Samenwerkingsverband Noord-Nederland (Cooperation Northern Netherlands) and the European Fund for Regional Development (EFRO) RIJKSUNIVERSITEIT GRONINGEN Resolutions of Racemates by Crystallization Additives and Attrition Proefschrift ter verkrijging van het doctoraat in de Wiskunde en Natuurwetenschappen aan de Rijksuniversiteit Groningen op gezag van de Rector Magnificus, dr. F. Zwarts, in het openbaar te verdedigen op vrijdag 20 november 2009 om 16:15 uur door Michel Sebastiaan Leeman geboren op 9 augustus 1978 te Emmen Promotores Prof. dr. ir. A.J. Minnaard Prof. dr. R.M. Kellogg Beoordelingscommissie: Prof. dr. J.G. de Vries Prof. dr. E. Vlieg Prof. dr. G. Coquerel ISBN: 978-90-367-3843-9 (printed version) ISBN: 978-90-367-3842-2 (electronic version) The most exciting phrase to hear in science, the one that heralds new discoveries, is not 'Eureka!' but 'That's funny ...' Isaac Asimov (1920 - 1992) Opgedragen aan Anita Contents CHAPTER 1 INTRODUCTION ........................................................................................ 1 1.1 History .................................................................................................................... 2 1.2 Optically Pure Compounds in Our Daily Life ........................................................ 6 1.3 Calculations ............................................................................................................ 9 1.4 Methods for the Preparation of Optically Pure Compounds................................. 10 1.4.1 Chiral Pool ...................................................................................................... 10 1.4.2 Prochiral Substrates ........................................................................................ 12 1.4.2.1 Chiral Auxiliary .................................................................................................... 12 1.4.2.2 Biocatalysis ........................................................................................................... 12 1.4.2.3 Chemocatalysis ..................................................................................................... 13 1.4.3 Resolution of Racemates ................................................................................ 14 1.4.3.1 Chromatographic Resolution ................................................................................ 14 1.4.3.2 Kinetic Resolution ................................................................................................ 15 1.4.3.3 Direct Crystallization, ........................................................................................... 16 1.4.3.4 Resolution by Diastereomeric Salt Formation, ..................................................... 18 1.5 Dutch Resolution .................................................................................................. 20 1.6 Aim and Outline of This Thesis ........................................................................... 22 1.7 References ............................................................................................................ 23 CHAPTER 2 RESOLUTION BY CRYSTALLIZATION ............................................. 31 2.1 Introduction .......................................................................................................... 32 2.2 Crystal Growth from Solution .............................................................................. 32 2.2.1 Primary Nucleation ......................................................................................... 32 2.2.2 Polymorphism ................................................................................................. 34 2.2.2.1 (Dis)appearing Polymorphs .................................................................................. 36 2.2.2.2 Polymorphism in Chocolate .................................................................................. 36 2.2.3 Nucleation Inhibition ...................................................................................... 37 2.2.4 Crystal Growth and Habit Modifiers .............................................................. 39 2.3 Phase Diagrams: a Necessary Evil on the Path to Salvation/Solvation ................ 40 2.3.1 Construction of a Ternary Phase Diagram ...................................................... 41 2.3.2 Conglomerates, Racemic Compounds and Solid Solutionsc .......................... 43 2.3.2.1 Finding Conglomerates ......................................................................................... 44 2.3.3 Phase Diagrams and Diastereomers ................................................................ 45 2.3.4 End Solid Solutions, Solvates and Hydrates ................................................... 46 2.3.5 Binary versus Ternary Phase Diagrams, ......................................................... 47 2.4 References ............................................................................................................ 48 CHAPTER 3 RESOLUTION OF RACEMATES BY DIASTEREOMERIC SALT FORMATION WITH THE AID OF NUCLEATION INHIBITORS. .......................... 53 3.1 Introduction .......................................................................................................... 54 3.2 Resolution with Optically Pure Mandelic Acid .................................................... 55 3.2.1 Screening for Possible Candidates .................................................................. 55 3.2.2 Nucleation Inhibitors Based on the Resolving Agent ..................................... 58 3.2.3 Nucleation Inhibitors Based on the Racemate ................................................ 62 3.2.4 Nucleation Inhibition in Ternary Phase Diagrams .......................................... 66 3.2.5 Upscaling of the Resolution ............................................................................ 69 3.3 Pope-Peachey and Nucleation Inhibitors .............................................................. 71 3.4 Experimental Section ........................................................................................... 74 3.5 References ............................................................................................................ 84 CHAPTER 4 THE EFFECT OF ADDITIVES ................................................................ 89 4.1 Introduction .......................................................................................................... 90 4.2 Resolution of (±)-PEA with DBTA ...................................................................... 90 4.3 Resolution of (±)-PEA with TA ........................................................................... 93 4.4 Dissolution by Abrasive Grinding ........................................................................ 97 4.4.1 Dissolution of Diastereomers in Saturated Mixtures ...................................... 97 4.4.2 Dissolution of Enantiomers in Saturated Mixtures ....................................... 102 4.5 Simultaneous Resolution with Cyclic Phosphoric Acids ................................... 103 4.5.1 Phencyphos ................................................................................................... 104 4.5.2 Anicyphos and Chlocyphos .......................................................................... 106 4.6 Experimental Section ......................................................................................... 108 4.7 References .......................................................................................................... 113 CHAPTER 5 DERACEMIZATION BY ABRASIVE GRINDING ............................. 117 5.1 Introduction ........................................................................................................ 118 5.2 Racemizable Conglomerate ................................................................................ 119 5.3 Deracemization by Abrasive Grinding ............................................................... 120 5.4 Deracemization by Sonication ............................................................................ 122 5.5 Deracemization by Crystallization ..................................................................... 122 5.6 Deracemization and Co-crystallization .............................................................. 126 5.6.1 Second Harmonic Generation ....................................................................... 128 5.6.2 Deracemization with Multiple Compounds .................................................. 129 5.7 Experimental Section ......................................................................................... 132 5.8 References .......................................................................................................... 139 CHAPTER 6 THE RESOLUTION OF PHENCYPHOS. ............................................ 143 6.1 Introduction ........................................................................................................ 144 6.2 Screening of Resolving Agents .......................................................................... 145 6.2.1 Diastereomeric Salt Formation with One Half Equivalent of Resolving Agent . .....................................................................................................................
Load more

Recommended publications
  • Improved Catalytic Performance of Carrier-Free Immobilized Lipase by Advanced Cross-Linked Enzyme Aggregates Technology
    Improved Catalytic Performance of Carrier-Free Immobilized Lipase by Advanced Cross-Linked Enzyme Aggregates Technology Xia Jiaojiao Jiangsu University of Science and Technology: Jiangsu University Yan Yan Jiangsu University Bin Zou ( [email protected] ) Jiangsu University https://orcid.org/0000-0003-3816-8776 Adesanya Idowu Onyinye Jiangsu University Research Article Keywords: lipase, carrier-free, immobilization, ionic liquid, stability Posted Date: May 24th, 2021 DOI: https://doi.org/10.21203/rs.3.rs-505612/v1 License: This work is licensed under a Creative Commons Attribution 4.0 International License. Read Full License Page 1/20 Abstract The cross-linked enzyme aggregates (CLEAs) are one of the technologies that quickly immobilize the enzyme without a carrier. This carrier-free immobilization method has the advantages of simple operation, high reusability and low cost. In this study, ionic liquid with amino group (1-aminopropyl-3- methylimidazole bromideIL) was used as the novel functional surface molecule to modify industrialized lipase (Candida rugosa lipase, CRL). The enzymatic properties of the prepared CRL-FIL-CLEAs were investigated. The activity of CRL-FIL-CLEAs (5.51 U/mg protein) was 1.9 times higher than that of CRL- CLEAs without surface modication (2.86 U/mg protein). After incubation at 60℃ for 50 min, CRL-FIL- CLEAs still maintained 61% of its initial activity, while the value for CRL-CLEAs was only 22%. After repeated use for ve times, compared with the 22% residual activity of CRL-CLEAs, the value of CRL-FIL- CLEAs was 51%. Further kinetic analysis indicated that the Km values for CRL-FIL-CLEAs and CRL-CLEAs were 4.80 mM and 8.06 mM, respectively, which was inferred that the anity to substrate was increased after modication.
    [Show full text]
  • From Synthetic Chemistry and Stereoselective Biotransformations
    PP Periodica Polytechnica From Synthetic Chemistry and Chemical Engineering Stereoselective Biotransformations to Enzyme Biochemistry – The Bioorganic Chemistry Group at the Budapest 59(1), pp. 59-71, 2015 University of Technology and Economics DOI: 10.3311/PPch.7390 Creative Commons Attribution b Zoltán BOROS1, Gábor HORNYÁNSZKY1, József NAGY1, László POPPE1 * research article Received 04 March 2014; accepted after revision 05 May 2014 Abstract 1 Introduction The activity of Bioorganic Chemistry Group (BCG) within 1.1 Scientific background of the Bioorganic Chemistry Department of Organic Chemistry and Technology at Budapest Research Group University of Technology and Economics is related to various The activity of Bioorganic Chemistry Group (BCG) of areas of synthetic chemistry, biotechnology and enzymology. Department of Organic Chemistry and Technology at Budapest This review gives an overview on the research activity of the University of Technology and Economics is related to various group covering development of synthetic organic chemistry areas of synthetic chemistry, selective biocatalysis [1] and methods; stereoselective biotransformations with lipases, enzymology with major emphasis on development of novel ammonia-lyases and further biocatalysts in batch and tools for stereoselective synthesis [2]. continuous-flow reactions; novel enzyme immobilization One of the main challenges facing organic chemistry is methods; and enzyme structural and mechanistic studies by the rational synthesis of an ever growing number of complex, experimental and computational techniques. optically active natural products and their analogues [3]. According to the regulation of FDA production of chiral Keywords drugs, agrochemicals, fine chemicals has been allowed in synthetic organic chemistry, stereoselective biotransformation, enantiomerically pure form, because it often happens that only continuous-flow reaction, lipase, ammonia-lyase, enzyme one of the two enantiomers shows the required therapeutical immobilization, enzyme structure, enzyme mechanism, QM/ effect [4].
    [Show full text]
  • Chiral Auxiliaries and Optical Resolving Agents
    Chiral Auxiliaries and Optical Resolving Agents Most bioactive substances are optically active. For instance, if This brochure introduces a variety of chiral auxiliaries and a substance is synthesized as a racemic compound, its optical resolving agents. We hope that it will be useful for your enantiomer may show no activity or even undesired bioactivity. research of the synthesis of optically active compounds. Thus, methods to gain enantiopure compounds have been Additionally, TCI has some brochures introducing chiral developed. When synthesizing enantiopure compounds, the compounds for the chiral pool method in “Chiral Building Blocks”, methods are roughly divided into three methods. “Terpenes”, “Amino Acids” and other brochures. Sugar derivatives are also introduced in a catalog, “Reagents for Glyco Chemistry Chiral pool method: & Biology”, and category pages of sugar chains. Furthermore, The method using an easily available chiral compound as a TCI has many kinds of catalysts for asymmetric synthesis and starting material like an amino acid or sugar. introduce them in brochures such as “Asymmetric Synthesis” and Asymmetric synthesis: “Asymmetric Organocatalysts”, and other contents. The method to introduce an asymmetric point to compounds You can search our information through “asymmetric synthesis” without an asymmetric point. Syntheses using achiral as a keyword. auxiliaries are included here. Optical resolution: The method to separate a racemic compound into two ● Reactions with Chiral Auxiliaries enantiomers. The direct method using a chiral column and One of the most famous named reactions using chiral auxiliaries1) the indirect method to separate two enantiomers using is the Evans aldol reaction.2) This reaction is quite useful because optical resolving agents to convert into diastereomers are this reaction can efficiently introduce two asymmetric carbons into examples.
    [Show full text]
  • Separation of the Mixtures of Chiral Compounds by Crystallization
    1 Separation of the Mixtures of Chiral Compounds by Crystallization Emese Pálovics2, Ferenc Faigl1,2 and Elemér Fogassy1* 1Department of Organic Chemistry and Technology, Budapest University of Technology and Economics, 2Research Group for Organic Chemical Technology, Hungarian Academy of Sciences, Budapest, Hungary 1. Introduction Reaction of a racemic acid or base with an optically active base or acid gives a pair of diastereomeric salts. Members of this pair exhibit different physicochemical properties (e.g., solubility, melting point, boiling point, adsorbtion, phase distribution) and can be separated owing to these differences. The most important method for the separation of enantiomers is the crystallization. This is the subject of this chapter. Preparation of enantiopure (ee~100%) compounds is one of the most important aims both for industrial practice and research. Actually, the resolution of racemic compounds (1:1 mixture of molecules having mirror-imagine relationship) still remains the most common method for producing pure enantiomers on a large scale. In these cases the enantiomeric mixtures or a sort of their derivatives are separated directly. This separation is based on the fact that the enantiomeric ratio in the crystallized phase differs from the initial composition. In this way, obtaining pure enantiomers requires one or more recrystallizations. (Figure 1). The results of these crystallizations (recrystallizations) of mixtures of chiral compounds differ from those observed at the achiral compounds. Expectedly, not only the stereoisomer in excess can be crystallized, because the mixture of enantiomers (with mirror image relationship) follows the regularities established from binary melting point phase diagrams, and ternary composition solubility diagrams, respectively, as a function of the starting enantiomer proportion.
    [Show full text]
  • II. Stereochemistry 5
    B.Sc.(H) Chemistry Semester - II Core Course - III (CC-III) Organic Chemistry - I II. Stereochemistry 5. Physical and Chemical Properties of Stereoisomers Dr. Rajeev Ranjan University Department of Chemistry Dr. Shyama Prasad Mukherjee University, Ranchi 1 Syllabus & Coverage Syllabus II Stereochemistry: Fischer Projection, Newmann and Sawhorse Projection formulae and their interconversions. Geometrical isomerism: cis–trans and syn-anti isomerism, E/Z notations with Cahn Ingold and Prelog (CIP) rules for determining absolute configuration. Optical Isomerism: Optical Activity, Specific Rotation, Chirality/Asymmetry, Enantiomers, Molecules with two or more chiral-centres, Distereoisomers, Meso structures, Racemic mixture. Resolution of Racemic mixtures. Relative and absolute configuration: D/L and R/S designations. Coverage: 1. Types of Isomers : Comparing Structures 2. Optical Activity 3. Racemic Mixtures : Separation of Racemic Mixtures 4. Enantiomeric Excess and Optical Purity 5. Relative and Absolute Configuration 6. Physical and Chemical Properties of Stereoisomers 2 Stereochemistry Types of Isomers Dr. Rajeev Ranjan 3 Stereochemistry Determining the Relationship Between Two Non-Identical Molecules Dr. Rajeev Ranjan 4 Stereochemistry Comparing Structures: Are the structures connected the same? yes no Are they mirror images? Constitutional Isomers yes no Enantiomers Enantiomers Is there a plane of symmetry? All chiral centers will be opposite between them. yes no Meso Diastereomers superimposable Dr. Rajeev Ranjan 5 Stereochemistry Optical Activity: • The chemical and physical properties of two enantiomers are identical except in their interaction with chiral substances. • The physical property that differs is the behavior when subjected to plane-polarized light ( this physical property is often called an optical property). • Plane-polarized (polarized) light is light that has an electric vector that oscillates in a single plane.
    [Show full text]
  • Cross-Linked Protein Crystal Technology in Bioseparation and Biocatalytic Applications
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Aaltodoc Helsinki University of Technology, Department of Chemical Technology Technical Biochemistry Report 1/2004 Espoo 2004 TKK-BE-8 CROSS-LINKED PROTEIN CRYSTAL TECHNOLOGY IN BIOSEPARATION AND BIOCATALYTIC APPLICATIONS Antti Vuolanto Dissertation for the degree of Doctor in Science in Technology to be presented with due permission of the Department of Chemical Technology for public examination and debate in Auditorium KE 2 (Komppa Auditorium) at Helsinki University of Technology (Espoo, Finland) on the 20th of August, 2004, at 12 noon. Helsinki University of Technology Department of Chemical Technology Laboratory of Bioprocess Engineering Teknillinen korkeakoulu Kemian osasto Bioprosessitekniikan laboratorio Distribution: Helsinki University of Technology Laboratory of Bioprocess Engineering P.O. Box 6100 FIN-02015 HUT Tel. +358-9-4512541 Fax. +358-9-462373 E-mail: [email protected] ©Antti Vuolanto ISBN 951-22-7176-1 (printed) ISBN 951-22-7177-X (pdf) ISSN 0359-6621 Espoo 2004 Vuolanto, Antti. Cross-linked protein crystal technology in bioseparation and biocatalytic applications. Espoo 2004, Helsinki University of Technology. Abstract Chemical cross-linking of protein crystals form an insoluble and active protein matrix. Cross-linked protein crystals (CLPCs) have many excellent properties including high volumetric activity and stability. In this thesis CLPC technology was studied in bioseparation and biocatalytic applications. A novel immunoaffinity separation material, cross-linked antibody crystals (CLAC), was developed in this thesis for enantiospecific separation of a chiral drug, finrozole. Previously, the preparation of an antibody Fab fragment ENA5His capable of enantiospecific affinity separation of the chiral drug has been described.
    [Show full text]
  • Diastereomers Diastereomers
    Diastereomers Diastereomers: Stereoisomers that are not mirror images. enantiomer (R) (S) (S) (R) diastereomers diastereomer diastereomer enantiomer (R) (S) (R) (S) Diastereomers Diastereomers: Stereoisomers that are not mirror images. (R) enantiomer (S) (S) (R) diastereomer To draw the enantiomer of a molecule with chiral centers, invert stereochemistry at all chiral centers. (R) To draw a diastereomer of a molecule (R) with chiral centers, invert stereochemistry at only some chiral centers. Meso Compounds Meso: A molecule that contains chiral centers, but is achiral. 3 Are these molecules chiral? (R) (S) (These are diff eren t f rom th e 3 molecules I just showed; they have 2 -Cl’s, rather than 1 -Cl & 1 -OH. enantiomer (R) (S) (R) (S) These molecules are chiral mirror images of one another. (R,R) and (S,S) are not the same. Meso Compounds Meso: A molecule that contains chiral centers, but is achiral. 3 enantiomer ? (R) (S) (S) (R) no! 3 same molecule! enantiomer (R) (S) (R) (S) Meso Compounds Meso: A molecule that contains chiral centers, but is achiral. 3 enantiomer ? (R) (S) (S) (R) no! 3 same molecule! If a molecule • contains the same number of (R) and (S) stereocenters, and • those stereocenters have identical groups attached, then the molecule is achiral and meso. Meso Compounds Meso: A molecule that contains chiral centers, but is achiral. 3 same molecule (R) (S) (S) (R) 3 meso diastereomers meso diastereomer diastereomer enantiomer (R) (S) (R) (S) chiral chiral Properties of Enantiomers Most physical properties of enantiomers are identical. diethyl-(R,R)-tartrate diethyl-(S,S)-tartrate boiling point 280 °C 280 °C melting point 19 °C 19 °C density 1.204 g/mL 1.204 g/mL refractive index 1.447 1.447 i.e., chirality does not affect most physical properties.
    [Show full text]
  • The Racemate-To-Homochiral Approach to Crystal Engineering Via Chiral Symmetry-Breaking
    CrystEngComm The Racemate -to -Homochiral Approach to Crystal Engineering via Chiral Symmetry-Breaking Journal: CrystEngComm Manuscript ID: CE-HIG-02-2015-000402.R1 Article Type: Highlight Date Submitted by the Author: 04-Apr-2015 Complete List of Authors: An, Guanghui; Heilongjiang University, School of Chemistry and Materials Science Yan, Pengfei; Heilongjiang University, School of Chemistry and Materials Science Sun, Jingwen; Heilongjiang University, School of Chemistry and Materials Science Li, Yuxin; School of Chemsitry and Materials Science of Heilongjiang University, Yao, Xu; Heilongjiang University, School of Chemistry and Materials Science Li, Guangming; School of Chemsitry and Materials Science of Heilongjiang University, Page 1 of 12Journal Name CrystEngComm Dynamic Article Links ► Cite this: DOI: 10.1039/c0xx00000x www.rsc.org/xxxxxx ARTICLE TYPE The Racemate-to-Homochiral Approach to Crystal Engineering via Chiral Symmetry-Breaking Guanghui An, a Pengfei Yan, a Jingwen Sun, a Yuxin Li, a Xu Yao, a Guangming Li,* a Received (in XXX, XXX) Xth XXXXXXXXX 20XX, Accepted Xth XXXXXXXXX 20XX 5 DOI: 10.1039/b000000x The racemate-to-homochiral approach is to transform or separate the racemic mixture into homo chiral compounds. This protocol, if without an external chiral source, is categorized into chiral symmetry- breaking. The resolution processes without chiral induction are highly important for the investigation on the origin of homochirality in life, pharmaceutical synthesis, chemical industrial and material science. 10 Besides the study on the models and mechanisms to explain the racemate-to-homochiral approach which may give the probable origin of homochirality in life, the recent developments in this field have been plotted towards the separation of enantiomers for the synthesis of pharmaceuticals, chiral chemicals.
    [Show full text]
  • Lectures 2014
    Selective Organic Synthesis KD 2390 (9 hp) Christina Moberg The advent of organic chemistry shaped the world • Biology is dependent on organic synthesis • Organic synthesis is the foundation for biotechnology, nanotechnology, pharmaceutical industry, and material industry About the course: • Disposition: lectures, exercises, lab, workshop • Course book: Clayden, Greeves and Warren Organic Chemistry, Oxford University Press, 2012 (ISBN 978-0-19-927029-3) [or Clayden, Greeves, Warren and Wothers: Organic Chemistry, Oxford University Press, 2001 (ISBN 0 19 850346 6)] and distributed material • Examination: oral exam, lab work (lab and workshop compulsory) After the course the student should be able to:" " • Describe basic stereochemical concepts • Describe principles for stereoselective synthesis, in particular for enantioselective synthesis • Explain the stereochemistry observed in chemical reactions • Suggest methods for stereoselective synthesis of simple organic compounds containing stereogenic elements • Identify suitable reagents for stereoselective transformations • Use retrosynthetic analysis for the construction of synthetic routes for simple organic compounds • Prepare organic compounds using advanced synthetic methodology Contents • Fundamental stereochemical concepts • Synthetic strategy and principles for stereoselective, in particular enantioselective, chemical transformations • Transition metal catalysis • Applications of frontier orbital theory • Retrosynthetic analysis • Advanced organic synthesis Marcellin Pierre Eugène Berthelot (1827 - 1907) " "La Chimie crée ses objets" “This is an important point: neither biology nor chemistry would be served best by a development in which all organic chemists would simply become biological such that, as a consequence, research at the core of organic chemistry and, therefore, progress in understanding the reactivity of organic molecules, would dry out. Progress at its core in understanding and reasoning in not only essential for organic chemistry itself, but for life sciences as a whole.
    [Show full text]
  • Practical Aspects on How to Deracemize Atropizomers by Means of Crystallization Ryusei Oketani
    Practical aspects on how to deracemize atropizomers by means of crystallization Ryusei Oketani To cite this version: Ryusei Oketani. Practical aspects on how to deracemize atropizomers by means of crystallization. Organic chemistry. Normandie Université, 2019. English. NNT : 2019NORMR109. tel-02502796 HAL Id: tel-02502796 https://tel.archives-ouvertes.fr/tel-02502796 Submitted on 9 Mar 2020 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. THÈSE Pour obtenir le diplôme de doctorat Spécialité Chimie Préparée au sein de l’Université de Rouen Normandie Practical aspects on how to deracemize atropisomers by means of crystallization (Aspects pratiques de la déracémisation d'atropisomères par cristallisation) Présentée et soutenue par Ryusei OKETANI Thèse soutenue publiquement le 06 Décembre 2019 devant le jury composé de M. Alexander BREDIKHIN Pr FRC Kazan Scientific Center of RAS Rapporteur M. Joop Ter HORST Pr University of Strathclyde Rapporteur M. Gérard COQUEREL Pr Université de Rouen Normandie Président Mme. Sylvie FERLAY-CHARITAT Pr Université de Strasbourg Examinateur M. Pascal CARDINAEL Pr Université de Rouen Normandie Directeur de thèse Thèse dirigée par Pascal CARDINAEL professeur des universités et Co-encadrée par le Dr. Clément BRANDEL au laboratoire Sciences et Méthodes Séparatives (EA3233 SMS) Contents Contents Contents .........................................................................................................................
    [Show full text]
  • Chapter 4: Stereochemistry Introduction to Stereochemistry
    Chapter 4: Stereochemistry Introduction To Stereochemistry Consider two of the compounds we produced while finding all the isomers of C7H16: CH3 CH3 2-methylhexane 3-methylhexane Me Me Me C Me H Bu Bu Me Me 2-methylhexane H H mirror Me rotate Bu Me H 2-methylhexame is superimposable with its mirror image Introduction To Stereochemistry Consider two of the compounds we produced while finding all the isomers of C7H16: CH3 CH3 2-methylhexane 3-methylhexane H C Et Et Me Pr Pr 3-methylhexane Me Me H H mirror Et rotate H Me Pr 2-methylhexame is superimposable with its mirror image Introduction To Stereochemistry Consider two of the compounds we produced while finding all the isomers of C7H16: CH3 CH3 2-methylhexane 3-methylhexane .Compounds that are not superimposable with their mirror image are called chiral (in Greek, chiral means "handed") 3-methylhexane is a chiral molecule. .Compounds that are superimposable with their mirror image are called achiral. 2-methylhexane is an achiral molecule. .An atom (usually carbon) with 4 different substituents is called a stereogenic center or stereocenter. Enantiomers Et Et Pr Pr Me CH3 Me H H 3-methylhexane mirror enantiomers Et Et Pr Pr Me Me Me H H Me H H Two compounds that are non-superimposable mirror images (the two "hands") are called enantiomers. Introduction To Stereochemistry Structural (constitutional) Isomers - Compounds of the same molecular formula with different connectivity (structure, constitution) 2-methylpentane 3-methylpentane Conformational Isomers - Compounds of the same structure that differ in rotation around one or more single bonds Me Me H H H Me H H H H Me H Configurational Isomers or Stereoisomers - Compounds of the same structure that differ in one or more aspects of stereochemistry (how groups are oriented in space - enantiomers or diastereomers) We need a a way to describe the stereochemistry! Me H H Me 3-methylhexane 3-methylhexane The CIP System Revisited 1.
    [Show full text]
  • Module No. 20: Methods of Resolution Subject
    Subject Chemistry Paper No and Title 1; Organic Chemistry-I (Nature of bonding and Stereochemistry) Module No and 21: Methods of Resolution Title Module Tag CHE_P1_M21 CHEMISTRY Paper No. 1: Organic Chemistry-I (Nature of bonding and Stereochemistry) Module No. 20: Methods of Resolution TABLE OF CONTENTS 1. Learning Outcomes 2. Introduction 3. Methods of Resolution 3.1 Resolution by mechanical Separation of Crystals 3.2 Resolution by formation of Diastereoisomers 3.3 Resolution by Formation of molecular Complexes 3.4 Resolution by Chromatography 3.5 Resolution Through Equilibrium Asymmetric Transformation 3.6 Resolution Through Asymmetric Transformation 3.7 Resolution by Biochemical Transformation 3.8 Resolution Through inclusion Compounds 3.9 Methods Based on NMR Spectroscopy 3.9.1 Use of Diastereomers 3.9.2 Use of Shift Reagents 3.9.3 Use of Chiral Solvating Agents 4. Summary CHEMISTRY Paper No. 1: Organic Chemistry-I (Nature of bonding and Stereochemistry) Module No. 20: Methods of Resolution 1. Learning Outcomes After studying this module, you shall be able to Know that pure form of isomers can be obtained from a racemic mixture. Understand the process of resolution. Learn about the different methods of resolution. Analyse the efficacy of various methods of resolution. 2. Introduction In the previous modules we have discussed in detail various types of isomers, viz., enantiomers, diastereomers, erythro and threo isomers etc. When an enantiomer is converted into a racemic mixture or a racemic modification (usually through chemical reactions), this process is known as racemisation. Conversely, when a racemic modification is separated into its constituent enantiomers, the process is known as resolution.
    [Show full text]