Stereoisomers - PDF

STEREOISOMERISM www.remixeducation.in  ISOMERISM isos meros Ethyl alcohol (CH3CH2OH) and Dimethyl ether (CH3OCH3) are isomers. www.remixeducation.in  Stereoisomers CONSTITUTIONAL ISOMERS Enantiomers...

STEREOISOMERISM www.remixeducation.in  ISOMERISM isos meros Ethyl alcohol (CH3CH2OH) and Dimethyl ether (CH3OCH3) are isomers. www.remixeducation.in  Stereoisomers CONSTITUTIONAL ISOMERS Enantiomers or Diastereomers Optical isomers Conformational Geometric Meso Epimers Ciss/trans Isomers compound www.remixeducation.in These differ from each other in the way their atoms are connected, i.e., in their structures. It’s six types signifying the main difference in the structural features of the isomers are: I. Chain/ Skeletal/ Nuclear Isomerism II. Position Isomerism III. Functional Isomerism IV. Metamerism V. Tautomerism VI. Ring Chain Isomerism www.remixeducation.in  These have same molecular formula but different arrangement of carbon chain within the molecule. CH3 H3C—CH2—CH2—CH3 C4H10 H3C—CH—CH3 n-Butane Same molecular 2-Methylpropane (Isobutane) (straight chain) formula (Branched chain) CH 3 CH 2 CH 2 CH 2 CH 3 n-Pentane CH 3 CH 3 H3 C C CH 3 C 5 H 12 H3 C CH CH 2 CH 3 Same 2-Methylbutane CH 3 molecular formula (Iso-pentane) 2, 2-Dimethylpropane (Neo-pentane) www.remixeducation.in differ in the position of attached atoms or groups or in position of multiple (double or triple) bonds. OH CH 3 CH 2 CH 2 OH CH 3 —CH—CH 3 Propan-1-ol (The OH group atC1) Propan-2-ol (The OH group atC2) 4 3 2 1 4 3 2 1 CH3CH2C CH CH3 C C CH3 But-1-yne (Triple bond at C1) But-2-yne (Triple bond at C2) www.remixeducation.in  different functional groups. CH 3 CH 2 OH CH 3 O CH 3 Dimethyl ether Ethanol O O CH3 C OH H C OCH3 Ethanoic acid Methyl methanoate O O and CH3 C CH3 CH3CH2 C H Propanone (Acetone) Propanal (Propionaldehyde) www.remixeducation.in  ( i. e., -O- , -S-, -NH-, - CO- etc.). Metamerism is shown by members of the same family, i.e., same functional groups. O O O CH3 CH3CH2—C—CH2CH3 is a metamer of CH3CH2CH2—C—CH3 or CH3—C—CHCH3 Pentan-3-one Pentan-2-one (Diethyl ketone) (Methyl n-propyl ketone) 3-Methylbutan-2-one (Isopropyl methyl ketone) CH3 CH3CH2—O—CH2CH3 is a metamer of CH3CH2CH2—O—CH3 or CH3CH2CH—O—CH3 Ethoxy ethane 1-Methoxy propane 2-Methoxypropane (Diethyl ether) (Methyl n-propyl ether) (Isopropyl methyl ether) www.remixeducation.in Structural or constitutional isomers existing in easy and rapid equilibrium by migration of an tautomers ( keto-enol tautomerism). www.remixeducation.in Open chain and cyclic compounds having the same molecular formula CH 3 CH CH 2 and Propene Cyclopropane CH 3 C CH and Propyne Cyclopropene www.remixeducation.in  formula but differ in the manner their atoms or groups are arranged in the space are called stereoisomers. It is of two types: I. Configurational Isomerism II. Conformational Isomerism www.remixeducation.in  interconverted unless a covalent bond is broken are called configurational isomers. These isomers can be separated under normal conditions. The configurational isomerism is again of two types: a) Optical Isomerism or Enantiomerism b) Geometrical Isomerism www.remixeducation.in  which are related to as an object and its non- superimposable mirror image are called optical isomers or enantiomers (Greek: enantion means opposite). The optical isomers can also rotate the plane of polarised light to an equal degree but in opposite direction. The property of rotating plane of polarised light is known as optical activity. The optical isomers have similar physical and chemical properties. www.remixeducation.in  Mirror COOH COOH H OH HO H CH3 CH3 ( -) - Lactic acid ( +) - Lactic acid (Rotates the plane of polarized (Rotates the plane of polarized light towards left hand side i.e. light towards right hand side i.e. anticlockwise) clockwise) www.remixeducation.in  www.remixeducation.in Geometric isomers These isomers are also called as cis- trans isomers. For example, molecular formula C 2H2Cl2 corresponds to two geometric isomers as follows:  can be interconverted rapidly at room temperature without breaking a covalent bond are called conformational isomers or conformers. Because such isomers can be readily interconverted, they cannot be separated under normal conditions. Two types of conformational isomers are: a) Conformational isomers resulting from rotation about single bond b) Conformational isomers arising from amine inversion www.remixeducation.in containing single bonds have many interconvertible conformational isomers.e.g, 'boat' and 'chair' forms of cyclohexane. H H H H H H H H H H H H H H H H H H H H H H H Cyclohexane Cyclohexane H (Chair form) (Boat form) www.remixeducation.in  "inside out" amine inversion Walden inversion R3 R3 R1 R2 N R1 N N R1 R3 R2 R2 Transition state www.remixeducation.in Measured with polarimeter Rotation, in degrees, is [] Clockwise rotation is called dextrorotatory Anti-clockwise is levorotatory www.remixeducation.in 19 The angle between the entrance and exit planes is the optical rotation. www.remixeducation.in  specific rotation,[ ]D []D = obser ved rotation (pathlength x concentration) =  = degrees Specific rotation is that obser ved for 1 g/mL in solution in cell with a 10 cm path using light from sodium metal vapor (589 nm) www.remixeducation.in 21 Enantiomers are known to possess same physical and chemical properties but they differ in the way they interact with plane polarised light. Substances which can rotate the plane of polarised light are said to be optically active. Dextrorotatory (Latin: dextre means right) and is indicated by (+) sign. Laevorotatory (Latin: laeves mean left) and is indicated by (-) sign. Those substance which do not rotate the plane of polarised light are called optically inactive. www.remixeducation.in Angle of rotation ( is the angle (degrees) by which the analyser is rotated to get maximum intensity of light. It depends upon: (i) Nature of the substance; (ii) Concentration of the solution in g/ml; (iii) Length of the polarimeter tube; (iv)  of the incident monochromatic light (598nm). (v) Temperature of the sample. www.remixeducation.in  Enatiomerism depends on whether a molecule in not superimposable on its mirror image. If it is superimposable, the molecule is optically inactive otherwise is optically active. The most convenient method of inspecting superimposability is to determine whether the molecule has any of the following three elements of symmetry: 1.Plane of symmetry (s) 2. Centre of symmetry (i) 3.Simple or proper axis of symmetry (Cn) www.remixeducation.in  an imaginary plane which divides a molecule in such a way that one half is mirror image of the other half. A molecule with atleast a plane of symmetry can be superimposed on its mirror image and is achiral. A molecule that does not have a plane of symmetry is usually chiral; it cannot be superimposed upon its mirror image COOH A plan of symmetry H OH may pass through Plane of atoms, between symmetry H OH atoms or both. COOH meso-Tartaric acid www.remixeducation.in The plane has the same thing on both sides for the flask There isnomirror planefor a hand www.remixeducation.in 42  A molecule that has a plane of symmetr y is achiral. www.remixeducation.in  CHRIAL - ral) [Greek : Cheir 'Handedness'] and the property of non- superimposability is called chirality. Thus our hands are chiral. Similarly, alphabets R, F,J are chiral and A, M, O are achiral. www.remixeducation.in  RR Chiral objects A A M M O O (Achiral objects) Chiral objects - human hand, gloves, shoes, etc. Achiral objects - a sphere, a cube, a button, socks without thumb, etc. Chirality or molecular dissymmetry is the necessary and sufficient condition for a molecule to be optically active. www.remixeducation.in  achiral chiral Enantiomers: nonsuperimposable mirror images, different molecules. One enantiomeric form of limonene smells like oranges, while its mirror image smells like lemons. The one enantiome r of carvone is the essence of caraway, and the other, the essence of spearmint. Most molecules in the plant and animal world are chiral and usually only one form of then enantiomer is found. Nineteen of the twenty known amino acids are chiral, and all of them are classified as left handed. www.remixeducation.in D and L Conversation:- www.remixeducation.in ▪ The relative configuration of the compound were established by obtaining them by a series of reactions from either D (+) glyceraldehyde or L(-) glyceraldehyde. These do not involve the breaking of a bond on chiral atom, the configuration about the chiral atom is retained. For example ,;acetic acid obtained from L-glyceraldehyde by a series of step has L-configuration and that obtained from D-glyceraldehyde has D- configuration. www.remixeducation.in ▪ The relative lactic acid also produced from D-glyceraldehyde is the same but it is levo-rotatory, while glyceraldehyde it self is dextro rotatory, www.remixeducation.in ▪ It should be noted that the notations D and L refer to the relative configuration, while d or(+) and l of (-) refer to the sign of optical rotation. A compound with D- configuration can be dextrorotatory [D(+)] levorotatory [D(-)].similarly a compound with L-configuration can be either [L(+)] or [L(-)].Thus the sign of rotation is not an indication of D(+) glyceraldehyde. In fact there are large number of compounds which have similar configurations but different signs of rotation. ▪ In 1951 X-ray diffraction results were employed to ascertain the absolute configuration of the molecules, which gave the same configuration to D-glyceraldehyde ,as was assigned by Emil Fiscer. www.remixeducation.in To overcome the problem of D-L system, R.S. Cahn (England), Sir Christopher Ingold (England), and V. Prelog (Zürich) evolved a new and unambiguous system for assigning absolute configuration to chiral molecules. This system is named as CIP (Cahn, Ingold, Prelog) system after their names. It is called as R-S system as the prefixes R-and S-are used to designate the configuration at a particular chirality centre. A racemic mixture is named as (RS). This system is based on certain rules called as sequence rules and also as CIP rules. www.remixeducation.in Cahn, Ingold and Prelog helped in introducing a new system for assigning the configurational form to the molecule. The system replaced the DL system. This system, adopted by IUPAC, is called the RS convention or the sequence rule system. In the sequence rule system, the four atoms or groups directly attached to the asymmetric carbon atom, are to be ranked and to be placed in a priority order. Use of the following rules was made to decide the priority order of the groups attached to the asymmetric carbon atom. www.remixeducation.in ◦ Each atom bonded to the stereocenter is assigned a priority, based on atomic number. The higher the atomic number, the higher the priority. ◦ Of the four atoms directly attached to the asymmetric carbon atom, the atom with the highest atomic number was given the highest priority and the atom with the lowest atomic number the lowest priority. 1 6 7 8 16 17 35 53 H CH3 NH2 OH SH Cl Br I Increasing Priority www.remixeducation.in 61 ◦ If priority cannot be assigned on the basis of the atoms bonded to the stereocenter, look to the next set of atoms. Priority is assigned at the first point of difference. 1 6 7 8 CH2 H CH2 CH3 CH2 NH2 CH2 OH Increasing Priority www.remixeducation.in  www.remixeducation.in 2. In case, the molecule has more than one group, having the same atom through which the groups are attached to the asymmetric carbon atom, then to decide the priority order between the groups the next atoms attached to the first atom are taken into consideration. For example in 2- butanol, CH3CHOHC2H5, the four different groups attached are – CH3, -C2H5, -OH and H. The highest priority group would be –OH and the lowest priority group would be H. As both the groups –CH3 and –C2H5, are attached to the asymmetric carbon atom through carbon therefore to decide the priority between these two the next atoms attached in the groups are to be taken into consideration. In –CH3 the next atoms are hydrogen whereas in –C2H5 the next atoms are one carbon and two hydrogens; therefore the priority goes to the ethyl group. ◦ Atoms participating in a double or triple bond are considered to be bonded to an equivalent number of similar atoms by single bonds H H C O C O O C www.remixeducation.in 64 1. 2. Assign a priority to each substituent from 1 (highest) to 4 (lowest) 3. Orient the molecule so that the group of lowest  priority (4) is directed away from you 4. Read the three groups projecting toward you in order from highest (1) to lowest priority (3) 5. If reading is clockwise, configuration is R (from the Latin rectus). If it is counterclockwise, configuration is S (from the Latin sinister). www.remixeducation.in 65 clockwise 1 2 2 counter 1 clockwise C C 4 4 3 3 view with substituent of lowest priority in back R (rectus) S (sinister) www.remixeducation.in  I1 I1 F C C 4 4F Br Cl Cl 2 Br 3 3 2 R Enantiomers S www.remixeducation.in 67 1. -OH HO H COOH HOOC H OH C 2. -COOH C 3. -CH3 CH3 CH3 4. -H (R)-(-)-lactic acid (S)-(+)-lactic acid www.remixeducation.in 68  3 2 4 F COOH H 2 1 Br 3H C 1 1 2 Cl 3 OH Br Cl H4 4 F3 H R-configuration R-configuration S-configuration Lowest priority 4 on horizontal li 3 2 CH3 CHO 4 1 4 1 H OH H OH 2 CH2CH3 3 CH2OH R-configuration S-configuration www.remixeducation.in  CHO CHO CHO H HO H H OH HO H H OH HO H HO CH2OH CH2OH CH2OH L-Erythrose D-Threose L-Threose (2S, 3S) (2S, 3R) (2R, 3S) www.remixeducation.in  A 50:50 mixture of two chiral or enantiomers compounds that are mirror images does not rotate light – called a racemic mixture (named for “racemic acid” that was the double salt of (+) and (-) tartaric acid The pure compounds need to be separated or resolved from the mixture (called a racemate) To separate components of a racemate (reversibly) we make a derivative of each with a chiral substance that is free of its enantiomer (resolving agent) This gives diastereomers that are separated by their differing solubility The resolving agent is then removed www.remixeducation.in Racemic mixture, also called racemate, a mixture of equal quantities of two enantiomers, or substances that have dissymmetric molecular structures that are mirror images of one another. Each enantiomer rotates the plane of polarization of plane-polarized light through a characteristic angle, but, because the rotatory effect of each component exactly cancels that of the other, the racemic mixture is optically inactive. The name is derived from racemic acid. Racemic acid, or, more properly, racemic tartaric acid, is a mixture of equal amounts of dextrorotatory and levorotatory tartaric acids; it is customarily designated D- or L-, or (+)- or (–)-, respectively, tartaric acid. www.remixeducation.in  1. Physical methods: - Spontaneous resolution - Inclusion compounds - Chromatography 2. Chemical methods: - Diastereomeric salt formation 3. Biochemical methods: - Enzymatic decomposition www.remixeducation.in  Usual methods of separation such as fractional distillation, fractional crystallization or adsorption techniques cannot be used for the separation of enantiomers. Therefore, some special procedures are needed for resolution of racemic mixtures. Some of the more important methods are: 1 Preferential Crystallization 2 Biochemical Method 3 Resolution through the formation of diastereomers: The Chemical Method Chromatographic Method www.remixeducation.in  crystallization is closely related to mechanical separation of crystals. A supersaturated solution of the racemic mixture is inoculated with a crystal of one of the enantiomers or an isomorphous crystal of another chiral compound. For example, when the saturated solution of (±) sodium ammonium tartarate is seeded with the crystal of one of the pure enantiomer or a crystal of (–) asparagine, (–) sodium ammonium tartarate crystalises out first. This method is also called as entrainment and the seed cystal is called entrainer. www.remixeducation.in  Microorganisms or enzymes are highly stereoselective. Fermentation of (±) tartaric acid in presence of yeast or a mold, e.g., Pencillium glaucum. The (+) tartaric acid is completely consumed leaving behind (–) tartaric acid. (±) Amino acids can be separated using hog- kidney acylase until half of acetyl groups are hydrolysed away, only acetyl derivative of L- amino acid is hydrolysed leaving behind acetyl derivative of D-amino acid. Limitations: (i)) These reactions are to be carried out in dilute solutions, so isolation of products becomes difficult. (ii)) There is loss of one enantiomer which is consumed by the microorganism. Hence only half of the compound is isolat d ( partially destructive method). www.remixeducation.in Basic Principle Step 1. optically pure reagent (+) or (–)-B to give amixture of two products which are diastereomers. The reagent (+) or (–)-B is called the resolving agent. (±) - A + (+)-B ,(+)A(+)B + (-)A(+)B Step 2. The mixture of diastereomers obtained above can be separated using the methods of Fractional distillation, fractional crystallization, etc. Step 3. The pure diastereomers are then decomposed each into the corresponding enantiomer and the original optically active reagent, which are then separated. www.remixeducation.in  (±) - Tartaric acid + ()-Cinchonidine (Racemic modification) (Resolving agent) (+) - Tartaric acid - () - cinchonidine Diastereomers + () - Tartaric acid - () - cinchonidine (separable) Separated by crystallization (+) - Tartaric acid - () - cinchonidine () - Tartaric acid - () - cinchonidin Dil.H 2 SO 4 Dil.H2 SO4 (+) - Tartaric acid () - Tartaric acid (crystallizes out) (crystallizes out) Similarly resolution of a (±) base with an optically active acid. HO (+) - base (+) - (+) - salt (+) - base + (+) - acid HO () - base () - (+) - salt () - base Diastereom ers Racemic (separable) www.remixeducation.in m odification  widely used both the enantiomers are obtained. successful if the following conditions are fulfilled: (i) The resolving agent should be optically pure. (ii) The substrate (racemic mixture) and the resolvingagent should have suitable functional groups for reaction to occur. (iii) The resolving agent should be cheap and be capable of regeneration and recycling. (iv) The resolving agent should be such which produces easily crysta llizable diastereomeric products.  Asymetric synthesis: ▪ Whenever the achiral compound is treated with an achiral reagent it results in the formation of racemic mixture. This is due to the reason that there are equal probabilities for the formation of the two enantiomers. For example when pyruvic acid is reacted with hydrogen and nickel the product is racemic lactic acid. This is due to the fact carbonyl group is planar and the addition of hydrogen from either side of the carbonyl group is equally possible, As a result, we get 1:1 mixture of enantiomers and hence racemic mixture is obtained. www.remixeducation.in ▪ However, if pyruvic acid is first esterified with an optically active alcohol such as (-) methyl alcohol and the optically active thus obtained is first reduced and then hydrolysed, we get predominantly (-) lactic acid. This is due to the fact that the direction of attack by the reagent is determined both the chiral centre already present in the molecule. www.remixeducation.in ▪ Thus, a method of directly preparing an optically active isomer from an achiral molecule under the influence of some other optically active substance is called asymmetric synthesis. ▪ It may be mentioned here that even in asymmetric synthesis both (+) and (-) enantiomers are formed but one of these is obtained in predominating amounts so that the product exhibits a net optical rotation. www.remixeducation.in 1. Retention : Bond at chiral carbon do not break : Configuration of substrate and product remains same 2. Inversion : Follows SN2 Mechanism. Isomer gets converted to other form 3. Racemisation : Second chiral center forms Diasteromer (SS , RS) www.remixeducation.in Stereoisomers - Compounds that have the same molecular formula and the same connectivity, but different arrangement of the atoms in 3- dimensional space. Stereoisomers cannot be converted into each other without breaking bonds. Stereoisomers can be subdivided into two general categories: enantiomers and diastereomers. Enantiomers are Stereoisomers whose molecules are non super imposable mirror images of each other. Diastereomers - Stereoisomers which are not enantiomers (or mirror images). Chiral or asymmetric carbon - A tetrahedral carbon atom bearing four different substituents. Chirality centers, or stereocenters - Asymmetrically substituted atoms in a molecular structure. www.remixeducation.in Meso compounds, or meso forms - Symmetric, or achiral molecules that contain stereocenters. Meso compounds and their mirror images are not stereoisomers, since they are identical. Optical activity - The ability of chiral substances to rotate the plane of polarized light by a specific angle. Dextrorotatory - Ability of chiral substances to rotate the plane of polarized light to the right. Levorotatory - Ability of chiral substances to rotate the plane of polarized light to the left. Specific rotation - The measured angle of rotation of polarized light by a pure chiral sample under specified standard conditions. Racemic mixture, racemic modification, or racemate - A mixture consisting of equal amounts of enantiomers. A racemic mixture exhibits no optical activity because the activities of the individual enantiomers are equal and opposite in value, therby canceling each other out. www.remixeducation.in www.remixeducation.in