DOCSLIB.ORG

Two Chiral Centres (Diastereoisomers) Mirror O O Two Enantiomers N S R N OH HO Differ by Absolute Configuration

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Two Chiral Centres (Diastereoisomers) Mirror O O Two Enantiomers N S R N OH HO Differ by Absolute Configuration 1 Two chiral centres (diastereoisomers) Mirror O O Two enantiomers N S R N OH HO differ by absolute configuration HN NH2 NH2 NH • A molecule with 1 stereogenic centre exists as 2 stereoisomers or enantiomers • Enantiomers have identical physical properties in an achiral environment • A molecule with 2 stereogenic centres can exist as 4 stereoisomers • Enantiomers (mirror images) still have identical physical properties • Diastereoisomers (non-mirror images) have different properties O2N O2N CO2Me CO2Me O O diastereoisomers trans cis enantiomers epoxide enantiomers epoxide mp = 141°C mp = 98°C different mp O2N O2N CO2Me CO2Me O O 123.702 Organic Chemistry 2 Diastereoisomers NH2 NH2 NH2 NH2 NH2 NH2 diastereoisomers 2HCl 2HCl 2HCl chiral different solubility meso solubility 0.1g/100ml EtOH seperable solubility 3.3g/100ml EtOH • Enantiomers differ only by their absolute stereochemistry (R or S etc) • Diastereoisomers differ by their relative stereochemistry • Relative stereochemistry - defines configuration with respect to any other stereogeneic element within the molecule but does NOT differentiate enantiomers • In simple systems the two different relative stereochemistries are defined as below: OH OH Me Me NH2 NH2 syn anti same face different face • A molecule can only have one enantiomer but any number of diastereoisomers • The different physical properties of diastereoisomers allow us to purify them • The differences between diastereoisomers will be the basis for everything we do... 123.702 Organic Chemistry 3 Diastereoisomers II OH CHO HO OH OH (2R,3R,4R)-2,3,4,5-tetrahydroxypentanal ribose OH OH OH OH CHO CHO CHO CHO HO HO HO HO four diastereoisomers OH OH OH OH OH OH OH OH (2R,3R,4R)-ribose (2R,3R,4S)-arabinose (2R,3S,4R)-xylose (2R,3S,4S)-lyxose mirror plane OH OH OH OH CHO CHO CHO CHO HO HO HO HO and their 4 enantiomers OH OH OH OH OH OH OH OH (2S,3S,4S)-ribose (2S,3S,4R)-arabinose (2S,3R,4S)-xylose (2S,3R,4R)-lyxose • If a molecule has 3 stereogenic centres then it has potentially 8 stereoisomers (4 diastereoisomers & 4 enantiomers) • If a molecule has n stereogenic centres then it has potentially 2n stereoisomers • Problem is, the molecule will never have more than 2n stereoisomers but it might have less... 123.702 Organic Chemistry 4 Meso compounds OH HO2C CO2H OH tartaric acid OH OH OH HO2C HO2C HO2C CO2H CO2H CO2H H 2 OH OH O OH C H H O H 2 OO diastereoisomers C enantiomers identical H O C C H 2 H 2 O O O O OH OH H H 2 H O C 2 C O HO2C HO2C H CO2H CO2H H OH OH O • Tartaric acid has 2 stereogenic centres. But does it have 4 diastereoisomers? • 2 diastereoisomers with different relative stereochemistry • 2 mirror images with different relative stereochemistry • 1 is an enantiomer • The other is identical / same compound • Simple rotation shows that the two mirror images are superimposable 123.702 Organic Chemistry 5 Meso compounds II • Meso compounds - an achiral member of a set of diastereoisomers that also includes at least one chiral member • Simplistically - a molecule that contains at least one stereogenic centre but has a plane of symmetry and is thus achiral • Meso compounds have a plane of symmetry with (R) configuration on one side and (S) on the other HO2C OH HO OH HO CO2H HO2C CO2H rotate LHS plane of symmetry • Another example... H Cl H H Cl H Cl Cl chiral achiral no plane of symmetry plane of symmetry non-superimposable superimposable on on mirror image mirror image (but it is symmetric!) (meso) 123.702 Organic Chemistry 6 Chiral derivatising agents • Difference in diastereomers allows chiral derivatising agents to resolve enantiomers enantiomerically pure mixture of derivatising agent diastereoisomers R* R / S R–R* + S–R* racemic mixture diastereoisomers separable S–R* R* R R–R* pure cleave pure enantiomer diastereoisomer diastereoisomer • Remember a good chiral derivatising agent should: • Be enantiomerically pure (or it is pointless) • Coupling reaction of both enantiomers must reach 100% (if you are measuring ee) • Coupling conditions should not racemise stereogenic centre • Enantiomers must contain point of attachment • Above list probably influenced depending whether you are measuring %ee or preparatively separating enantiomers 123.702 Organic Chemistry 7 Chiral derivatising agents: Mosher’s acid OH F3C OMe DCC, DMAP F3C OMe H CH2Cl2, –10°C O Me + CO2H O N C R / S S N R–S & S–S DCC - dicyclohexylcarbodiimide • Popular derivatising agent for alcohols and amines is α-methoxy-α- trifluoromethylphenylacetic acid (MTPA) or Mosher’s acid • Difference in nmr signals between diastereoisomers (above): 1H nmr Δδ = 0.08 (Me) 19 .................................................................................................. F nmr Δδ = 0.17 (CF3) • Typical difference in chemical shifts in 1H nmr 0.15 ppm • 19F nmr gives one signal for each diastereoisomer • No α-hydrogen so configurationally stable • Diastereoisomers can frequently be separated • In many cases use of both enantiomers of MTPA can be used to determine the absolute configuration of a stereocentre (73JACS512, 73JOC2143 & 91JACS4092) 123.702 Organic Chemistry 8 Chiral derivatising agents: salts OTol HO2C O NH CO2H OTol O NH2 OTol OH OH O2C CO2H OTol R / S S diastereoisomer is insoluble so easily removed by filtration NaOH O NH OH (–)-propranolol β-blocker • No need to covalently attach chiral derivatising group can use diastereoisomeric ionic salts • Benefit - normally easier to recover and reuse reagent • Use of non-covalent interactions allows other methods of resolving enantiomers... 123.702 Organic Chemistry 9 Resolution of enantiomers: chiral chromatography • Resolution - the separation of enantiomers from either a racemic mixture or enantiomerically enriched mixture • Chiral chromatography - Normally HPLC or GC • A racemic solution is passed over a chiral stationary phase • Compound has rapid and reversible diastereotopic interaction with stationary phase • Hopefully, each complex has a different stability allowing separation ‘matched’ ‘matched’ enantiomer - more enantiomer stable (3 interactions) travels slowly ‘mis-matched’ ‘mis-matched’ enantiomer - less enantiomer stable (1 interaction) readily eluted racemic mixture chiral stationary in solution phase 123.702 Organic Chemistry 10 Chiral chromatography R/S inject mixture on to column R S R O O O Si O S Si O chiral column O H O O Si N prepared from a Si O Me Si O Si NO2 R suitable chiral O Me O stationary phase O (many different types) NO2 S silica chiral amine R chiral stationary phase • Measurements of ee by HPLC or GC are quick and accurate (±0.05%) • Chiral stationary phase may only work for limited types of compounds • Columns are expensive (>£1000) • Need both enantiomers to set-up an accurate method 123.702 Organic Chemistry 11 NMR spectroscopy: chiral shift reagents • Chiral paramagnetic lanthanide complexes can bind reversibly to certain chiral molecules via the metal centre • Process faster than nmr timescale and normally observe a downfield shift (higher ppm) • Two diastereomeric complexes are formed on coordination; these may have different nmr signals C3F7 O + substrate Eu(hfc)3•••substrate O EuL2 Eu(hfc)3 • Problems - as complexes are paramagnetic, line broadening is observed (especially on high field machines) • Compound must contain Lewis basic lone pair (OH, NH2, C=O, CO2H etc) • Accuracy is only ±2% 123.702 Organic Chemistry 12 Chiral shift reagents II O O 3+ O Sm O γ α CO2H O N N O β NH2 H O Me O L-valine • New reagents are being developed all that time that can overcome many of these problems • 1H NMR spectra (400 MHz) of valine (0.06 M, [D]/[L] = 1/2.85) in D2O at pH 9.4 123.702 Organic Chemistry 13 Enzymatic resolution lipase PS from Pseudomonas O cepacia, 0.05M phosphate buffer, O O pH 7, 0.1M NaOH, 5°C Bu Bu + Bu OEt OEt O Na 60% conversion F F F R / S R S >99% ee 69% ee soluble in soluble in organic phase aqueous phase • Enzymes are very useful for the resolution of certain compounds • Frequently they display very high selectivity • There can be limitations due to solubility, normally only one enantiomer exists and can be too substrate specific • Below is the rationale for the selectivity observed above... enzyme H N N H R O O Bu O O O Et his N diastereomeric interaction of enzyme H F H lone pair with σ* orbital of C–F of (S)- O enantiomer favoured over interaction ser with (R)-enantiomer 123.702 Organic Chemistry.
Load more

Recommended publications
  • 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]
  • Enantioselective Synthesis of the (1S,5R)-Enantiomer of Litseaverticillols a and B
    Biosci. Biotechnol. Biochem., 70 (10), 2564–2566, 2006 Note Enantioselective Synthesis of the (1S,5R)-Enantiomer of Litseaverticillols A and B y Akira MORITA, Hiromasa KIYOTA, and Shigefumi KUWAHARA Laboratory of Applied Bioorganic Chemistry, Graduate School of Agricultural Science, Tohoku University, Tsutsumidori-Amamiyamachi, Aoba-ku, Sendai 981-8555, Japan Received May 8, 2006; Accepted May 31, 2006; Online Publication, October 7, 2006 [doi:10.1271/bbb.60253] An enantioselective synthesis of the (1S,5R)-enan- which have recently culminated in the first enantiose- tiomer of litseaverticillols A and B was accomplished in lective total synthesis of (1R,5S)-(À)-1 and (1R,5S)-(À)- line with our previously reported synthetic pathway for 2.4) In this note, we describe the synthesis of their their (1R,5S)-enantiomer. The use of ‘‘EtSCeCl2’’ pre- enantiomers directed toward an evaluation of the differ- pared from EtSLi and CeCl3, instead of previously ence in biological activity between the enantiomers of employed EtSLi itself, for the formation of thiol ester litseaverticillols A and B. intermediates prevented any undesirable epimerization Our synthesis of (1S,5R)-1 and (1S,5R)-2 basically occurring in the process. followed our previous synthesis of their corresponding enantiomers, (1R,5S)-1 and (1R,5S)-2, respectively,4) Key words: litseaverticillol; enantioselective synthesis; except that (R)-4-benzyloxazolidin-2-one was employed sesquiterpenoid; anti-HIV as the source of chirality, instead of its (S)-form used in the previous synthesis. Homogeranic
    [Show full text]
  • Lecture 3: Stereochemistry and Drugs Key Objectives: 1
    Lecture 3: Stereochemistry and drugs Key objectives: 1. Be able to explain the role of stereochemistry in drug action or metabolism 2. Be able to identify a chiral center (or centers) in a drug 3. Be able to explain the difference between enantiomers and diastereomers Value of chirality and stereochemistry: Chirality as expressed through stereoisomers increases the specificity of molecule recognition and signaling. Like a key in a lock, or a hand in a glove. Some useful definitions: Chirality (and chiral centers): An object (such as a molecule) that is asymmetric and therefore not superimposable on its own image. Chiral centers are the most common features within molecules that give rise to chirality. Stereoisomer: A molecule that possesses at least one chiral center (or center of chirality). Enantiomers: A type of stereoisomer that exists in mirror image forms. See Figure 1. Diastereomers: A type of stereoisomer that possesses more than one chiral center. Stereospecific: A term used to describe a stereochemical property that one isomer possesses but the other does not. For example, the stereospecific metabolism of the S-enantiomer of a compound by an enzyme but the R-enantiomer is not metabolized by that enzyme. Stereoselective: A term used to describe a stereochemical property that is shared by both stereoisomers, but the property is greater in one isomer than the other. For example, the stereoselective binding of the R-enantiomer for a receptor indicates that the S-enantiomer also binds but not as avidly as the R-enantiomer. Enantiomers Figure 1: For enantiomers, many times we use the example of our left and right hands to demonstrate their asymmetry.
    [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]
  • Enantiomers & Diastereomers
    Chapter 5 Stereochemistry Chiral Molecules Ch. 5 - 1 1. Chirality & Stereochemistry An object is achiral (not chiral) if the object and its mirror image are identical Ch. 5 - 2 A chiral object is one that cannot be superposed on its mirror image Ch. 5 - 3 1A. The Biological Significance of Chirality Chiral molecules are molecules that cannot be superimposable with their mirror images O O ● One enantiomer NH causes birth defects, N O the other cures morning sickness O Thalidomide Ch. 5 - 4 HO NH HO OMe Tretoquinol OMe OMe ● One enantiomer is a bronchodilator, the other inhibits platelet aggregation Ch. 5 - 5 66% of all drugs in development are chiral, 51% are being studied as a single enantiomer Of the $475 billion in world-wide sales of formulated pharmaceutical products in 2008, $205 billion was attributable to single enantiomer drugs Ch. 5 - 6 2. Isomerisom: Constitutional Isomers & Stereoisomers 2A. Constitutional Isomers Isomers: different compounds that have the same molecular formula ● Constitutional isomers: isomers that have the same molecular formula but different connectivity – their atoms are connected in a different order Ch. 5 - 7 Examples Molecular Constitutional Formula Isomers C4H10 and Butane 2-Methylpropane Cl Cl C3H7Cl and 1-Chloropropane 2-Chloropropane Ch. 5 - 8 Examples Molecular Constitutional Formula Isomers CH O CH C H O OH and 3 3 2 6 Ethanol Methoxymethane O OCH and 3 C H O OH 4 8 2 O Butanoic acid Methyl propanoate Ch. 5 - 9 2B. Stereoisomers Stereoisomers are NOT constitutional isomers Stereoisomers have their atoms connected in the same sequence but they differ in the arrangement of their atoms in space.
    [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]
  • Preferential Crystallization of a Racemic Compound Via Its Conglomerate Co-Crystals
    Preferential crystallization of a racemic compound via its conglomerate co-crystals Master Thesis Oscar F. Villamil R August 24th 2016 Faculty of 3ME Department: Process & Energy Section: Intensified Reaction & Separation Systems Graduation Committee Ir. W. Li PDeng Dr. ir. H.J.M Kramer Dr. ir. H.W.Nugteren Dr. ir. A. van der Heijden 1 Abstract Preferential crystallization, as a powerful chiral resolution technique, is intrinsically limited to chiral molecules that crystallize as conglomerates. Many studies have been conducted on using chemical reactions to convert the target molecules, which originally form racemic compounds, into conglomerate-forming derivatives salts or by creating solvate, for the application of preferential crystallization. Up to this date conglomerate co-crystals of racemic compounds have never been applied as the intermediate for chiral resolution. In this study, preferential crystallization of the model compound Ibuprofen (IBU), originally a racemic compound, was carried out via its conglomerate co-crystal with 2,4-bipyridine ethylene (BPE) in heptane. Suitable operation conditions were selected based on pseudo- binary phase diagram of the model compound system constructed under different IBU-BPE ratio. A unique measurement method combining polarimeter and Nuclear Magnetic Resonance (NMR) measurements was developed to identify the enantiopurity and the yield of the final product, which was a mixture of racemic IBU and IBU-BPE co-crystals, a likely result from this complex system. With respect to the results, preferential crystallization of IBU was successfully performed by slowly cooling down a saturated solution of racemic IBU-BPE, initially at T=57.5°C, after seeding it with S-IBU/BPE crystals to T=53°C with a cooling rate of 0.3°C/min.
    [Show full text]
  • A Review on Chiral Chromatography and Its Application to the Pharmaceutical Industry
    Chemsearch Journal 2(1): 8 - 11 Publication of Chemical Society of Nigeria, Kano Chapter CHIRAL CHROMATOGRAPHY AND ITS APPLICATION TO THE PHARMACEUTICAL INDUSTRY: A REVIEW Mudi, S. Y. and *Muhammad, A. Department of Pure and Industrial Chemistry, Bayero University, PMB 3011, Kano. *Correspondence author: [email protected] ABSTRACT Chiral chromatographic enantioseparation has been in practice by researchers. There has been a considerable interest in the synthesis and separation of enantiomers of organic compounds especially because of their importance in the biochemical and pharmaceutical industries. Often, these compounds are purified rather than being produced by chiral-specific synthesis. We herein present a general discussion that focuses on the chromatographic enantioseparation, which we hope will be useful to chromatographic and pharmaceutical industries. Keywords: Chiral chromatography, enantioseparation, pharmaceutical industry. INTRODUCTION giving differing affinities between the analytes Chromatography is the collective term for a set of (Schreier et al., 1995). laboratory techniques for the separation of mixtures. It The main goal of this review is to provide a brief involves passing a mixture dissolved in a "mobile overview of chiral separations to researchers who phase" through a “stationary phase”, which separates are versed in the area of analytical separations but the analyte from other compounds in the mixture unfamiliar with chiral separations. This review based on differential partitioning between the mobile highlights significant issues of the chiral and stationary phases. Subtle differences in a separations and provides salient examples from compound's partition coefficient result in differential specific classes of chiral selectors where retention on the stationary phase and thus effecting appropriate. the separation (Laurence and Christopher, 1989; Pascal et al., 2000).
    [Show full text]
  • Distinction of Enantiomers by NMR
    REVIEWS Disinction of enantiomers by NMR spectroscopy using chiral orienting media Burkhard Luy Abstract | NMR spectroscopy is a very important analytical tool in modern organic and inorganic chemistry. Next to the identification of molecules and their structure determination, it is also used for the distinction of enantiomers and the measurement of enantiomeric purity. This article gives a brief review of the techniques being developed for enantiomeric differentiation by virtue of chiral alignment media and their induction of enantiomerically dependent anisotropic NMR parameters like residual dipolar couplings. An overview of existing chiral alignment media, a brief introduction into the basic theory and measurement of the various anisotropic parameters, and several example applications are given. 1. Introduction valuable compounds one doesn’t necessarily want to NMR spectroscopy is one of the most important irreversibly modify the substance. analytical tools in modern organic and inorganic Another possibility for the distinction of chemistry as it is the only tool that allows the enantiomers is the orientation of the molecule of determination of molecular structures at atomic interest in a so-called chiral alignment medium. resolution in solution. It is used to identify the In this case, the molecule is partially aligned constitution, conformation and configuration and anisotropic NMR parameters like residual of countless molecules every day. However, the quadrupolar couplings, residual dipolar couplings magnetic field used for the induction of the Zeeman and residual chemical shift anisotropy can be splitting is per se achiral so that enantiomers measured2–4. As the orientation in a chiral have identical properties and therefore identical alignment medium is different for the two NMR spectra.
    [Show full text]