INTRODUCTION. Stereocherrstry helps to define the structure of a molecule and ofientation ofthe atoms ‘and functional groups present, in three dimensions. Stereoisomers possess the same ‘molecular and structural formulae and the same functional groups but dffer in the three- dimensional spatial orientation of these atoms or groups within the molecule. Due to the difference in orientation of the functional group and geometry of the molecule, stereoisomers differ in their physical, chemical, physicochemical and biochemical properties. Based on symmetry and energy criteria, stereoisomers are divided into three classes. (a) Geometrical isomers (©) Optical isomers (©) Conformational isomers. (0) Geometrical isomers (ct-trans isomerism): Malai acid (mp. 120°C) and furnace acid (mp. 287°C) have the same molecular formula but differ in the arrangement of functional groups around double bond. They have different physical ang, to some extent, chemical properties. This type of isomerism is known as geometrical isomerism. Hooe, pooH \gae/ / exe na coon Matec ts Fumarc ald (blondie 8) (vane bdnedil acd) The presence of a carbon-carbon double bond restricts the freedom of rotation about double bond. The designation cis (Latin word: same side), is used to denote the presence of like atoms or groups on the same side and trans (Latin word, across) is used when they are ‘on opposite sides. Isomerism seen in non-cyclic, open-chain compound due to the presence ‘of a double bond, is called a ® diastereoisomerism while when it occurs in a cyclic ‘skeleton lacking a double bond, itis termed as 6 diastereoisomerism. i jam ; Isomers which differ only in their behaviour towards plane potions ical isomers ner rotates the plane of polarised light towards right and the other towards left to the same extent. Such pair of isomers are called optical isomers and the Phenomenon is called optical activity. In order to understand the phenomenon of optical isomerism and optical activity, we Must know the following terms : a) Plane polarised light : An ordinary ray of light consists of electromagnetic ¢ tions of ition eaiaenn These radiations vibrate in all planes at right angles direction in which it travels. Monochromatic light consists of waves of a particular ( wavelength and these waves also vibrates in all planes. When monochromatic light is passed through a Nicol prism (prism made from a lar crystalline form of CaCO, known as calcite), the light coming out of the prism has tions in only one plane, So, plane polarised light is defined asa beam of light having vibra only in one plane. The Nicol prism used to obtain plane polarized light is called a polarizer. *&% -N — Ill Ordinary Light Necol Pasm Plano Polarised Lightb) Optical activity : The optical activity was discovered by the French Chemist, Louis) Pasteur in 1848. He studied that when a concentrated sodium ammonium tartrate solution was allowed to crystallize, two types of crystals separated out. Each type of crystals when dissolved in water rotated the plane of polarised light. This observation led to the discovery of optical activity. Substances which can rotate the plane of polarised light through a certain angle are called optically active substances and this property of a substance by virtue of which the organic substances rotate the plane polarised light is called! as optical activity. If the plane polarised light shows no change in angle it means that the substance is optically inactive. ‘The optically active compounds can rotate the plane polarised light either towards right hand side or left hand side. The compounds which can rotate the plane of polarised light towards right side (clockwise direction) are called dextro rotatory and is represented by prefix (+) or “d” whereas the compounds which can rotate the plane of polarised Tight 1 wards left side (anticlockwise direction) are called laevorotatory and is represented by pre fix) or 1”. © Angle of Rotation and Specific Rotation : The angle (in degrees) through which the plane polarized light is rotated by an optically active substance is called as angle of rotate Fis denoted by o The instrument which is used for measuring the angle of rotation of the plane polarised light is known as Polarimeter. ; 'A Polarimeter contains a light source (sodium lamp), two Nicol prisms and a polarity eter tube, The first Nicol prism which is near to the source is called polarizer and the szzond | ‘Nicol prism is called the analyzer. The axis of polarizer is fixed while that of ee aol | changed. Polarimeter tube is placed between the polarizer and the analyzer, which con | the solution of optically active substance oad The arrangement of polarizer and analyzer with their axes perpendicular to each OFT is used fo stucly the effect of optically active compounds towards plane polarized light. Por example, the optically active compound is placed in polarimeter tube, if some light appears indicates that compound has rotated plane polarised light through certain angle.@-Q-m -Oo-Ne eter kathy — relay PoMITne Fear Naam ‘Schematic Representation of Polarimeter and Optical Activity The angle of rotation d angle fronton depends upon eros fates he lature of optically active substance 2) Nature of the solvent 3) Concentration of solution 4) Wavelength of monochromatic light used 5) Length of the polarimeter tube containing the sample 6) Temperature of the solution te spi activity i expressed in tens of pei rotation, Spi oto is defined of rotation of plane polarised light produced by on optically active compound specified temperature and wavelength. It is denoted by la, where tis the temperature and Dis the wavelength of light used. Generally D line of sodium vapour lamp having a wave- length of 5893" is used as the source of monochromatic light. reciente gig ire ake min fou) length of the polarimeter tube (dm) C= Concentration of optically active substance (gm/m) syed that the molecular structure of all the optically ‘ature. A molecule is chiral or dissymmetric .ge. This property of non-super imposiility ret which is superimposable on its mirror 0" and “A” are achiral @) Chirality of molecules : It is obser ‘active compounds is chiral (dissymmettic) in ns only if itis non super imposable on its mirror {sclled chirality. In contrast a molecule oF an obje ic for eg. the english alphabet image is called achiral or symmetr “p* js chiral in nature. while the alphabet ° © —_Achiral 7] tnor image is A biol | Suporeposabla Pp gO] pensar Miror© e) Chiral and Asymmetric Carbon : This concept arises from the Leaked mat i Vant's Hoff assume that a sane bon atom in various organic compounds. In 1873 Carbon forms four bonds which ae directed towards the four comers of tetrahedron the four toms attached to the carbon ae diferent then i will produces disymmety, yeh » carbon is known as chiral or disymmetric carbon. It can. be represented as “ABP see are different groups. The mirror image of such carbon is non superimpossable as thoy below : A f° f | c c c a” | Ss of | oats c, He | >» P Br Br Non-Superimpossable Mirror Images If two atoms attached to the carbon atom are similar, the chirality is lost and the ecule becomes symmetrical. As a simple rotation through 180" about its axis will make compound superimpossable on its mirror image. For e.g, 2-chloropropane is an achiral m ecule. A chiral carbon is denoted by (7) on the carbon atom. For e.g, lactic acid (CHC COOH), 23-dihydroxy propanal (CHOH-C*HOH-CHO), are chiral and are optically active, From the above examples it is clear that the necessary and sufficient conditions fora epmpaund to be optically active is the presence of one or more chiral carbon atoms and the chirality of the molecule as a whole. [13 DIASTERIOISOMERISM Saison ‘Stereoisomers with two or more asymmetric or chiral carbons (stereocenter) will diasterioiscmerism, The stereoisomers that are neither mirror images of one another nor are superimposable, are known as diesterioisomers.For example: ° Each stereocenter gives to two different configurations. It means if a molecule contains ‘two asymmetric carbons, there ate upto four possible conformations. When two diastereoisomers differ from each other at only one stereacenter they are known as epimers. eg, D-threase and D-enythrose are epimers of each other. Unlike enantiomers, diastereoisomers have different physical and chemical properties. ‘COOH 1 OOH oe H. OH | OH: ‘OH eHon | Gaon caw | yeree In case of 3-bromo-2-butano|, we have four possible combinations as SS, RR, SR and RS. Qut of these, two molecules SS and RR are enantiomers of each other while the configurations RS and SR are diastereomers of SS and RR configurations. cH cH, Enaniomers (28, 38)3 Bromo-?-butanol_(2R, 3R}+-Bromo-2butanol Diestereomer Diastereomer cH, cH, Enaniomers (28, 3R|-3-Biomo-2-butanol _(2R, 38) 3-B;omo.2-butanal Thus in diastereoisomers, the chemical formula and atom connectivity remain the same bbut the three dimensional orientation or shape of the molecule is different eg., 2-bromo-3- chloro ethane.Cla ‘The molecules ate different in the configuration of chlorine atoms but same with the bromine atoms hence they are diastereomers. Similarly in cydic compound 3-ethyl1- chlorocyclohexane, ethyl groups have same configuration but the chlorine atoms have ‘opposite configuration. Hence, these molecules are diastereomers. Configurations differ at some stereocenters but not at others can not create mirror images. So they are not enantiomers, but are diastereomers. TR] <_Dissereomers ne Enantioner Enantiomer Diastereomers Diastecoomers Enastioner enantiomer sr |- __-[es Diasiereomers The diydrotestosterone molecule contains seven stereocentes. Applying 2" rue, gives 128 possible configurations. Out of these, only one is enantiomeric pair while rest are diastereomers. [1.4 MESO COMPOUNDS ‘When multiple stereocenters present in a molecule create an internal plane of symmetry, it leads to meso compounds. Tartaric acd contains two asymmetric centers which give rise to four configurations. But there are really only three stereoisomers of tartaric acid: a pair of chiral molecules (enantionmers of each other) and the achiral meso compound. In meso compound, we have internal mirror plane that splits the molecule into two symmetrical sides, the stereochemistry of both left and right side should be opposite to each other. This leads to auto cancellation of stereo actvity of each other resulting into optical inactivity. Hence, meso compounds can not be assigned with either dextrorotatory (+) oF levorotatory (©) designation. The internal mirror plane is simply a line of symmetry that bisects the ‘molecule. Each half is a mirror image of the other half. Each half must contain a stereocenter in order to be a meso compound. These stereocenters must also have different absoluteconfigurations Due to internal symmetry, they meso molecule is achiral. Hence, this configuration is not optically active. The meso form is also a type of diastereomer. The ‘remaining two isomers are enantiomeric pair (D-and L-form). ~ ; =“ 00H Ho- coon | Hoo” ou t cook LO) tartaric acl | 0) tartaric aed Meso form (Enentiomers) of tanarie sid The melting point of both enantiomers of tartaric acid is about 170°C while the meso- tartaric acid has the melting point of 145°C. A meso compound is ‘superimposable’ on its ‘mirror image. Examples in cyclic meso compounds include. In summary a meso compound should have two or more stereocenters, an internal ‘symmetry plane and the stereachemistry should be R and S ‘Table 1.1: Difference between enantiomer and diasteromers Sr. No. Parameter Enantiomer Diastereomer 1. | Number of stereocenters ‘One Two or more 2. | Mircor images Yes No 3. | Superimposition No No 4. | Physical properties Same Different 5. | Chemical properties Same Different Difference Between Diastereomers and Enantiomers Enantiomers Diastereomers They have a mirror image relationship. | 1. They do not have mirror image relationship. 2. They have similar physical properties _| 2. They have different physical properties like like melting point, boiling point etc. melting point, boiling point, solubility ee 3. They have identical chemical properties | 3. They have similar but not identical chemist except rate of reaction with chiral reagents} properties. is different ‘ jot 4 They cannot be separated by 4, They can be separated by fractional distilatos crystallisation, chromatography etc chromatography etc . 5. They are always optically active in 5. They can be optically active or optically nature. aoe ‘ inactive. sag wo or mo 6. This mostly present in compounds 6. IL is present in compounds having two ot having one chiral centre. dissimilar stereogenic centre.[1.6 NOMENCLATURE OF OPTICAL ISOMERS ‘The d/l system was developed by Fischer and Rosanoff in around 1900. Totally arbitrary, (+) glyceraldehyde was defined as being D because the OH group attached to the C is on the right hand side of the molecule. While (-) glyceraldehyde was defined as L because the (OH group is on the left hand side. won fon (A) The d/l system (named after Latin dexter and laevus, right and left) names the ‘molecule by relating them to the molecule glyceraldehyde. This system of nomenclature represents an older system for distinguishing enantiomers of amino acide and arbonydrates. This atbitrary type of configuration (d/l system) is known as Relative Configuration, (2) To name complex amino acids and carbohydrates in Fischer projection, take ‘carbonyl group (aldehyde, ketone or carboxylic acid) on the top and CH:OH on the bottom. (b) The D descriptor is used when the -OH or -NHy on the 2° carbon ([rom bottom) Points to the right and L is used when the -OH or -NH, points to the left. Thus, from stereochemistry of only one stereocenter (i.e. 2 carbon from bottom) the stereochemistry of all other stereocenters in the molecule is defined. (c) The dl nomenclature does not indicate which enantiomer is destrorotatory and Which is levoratatory Itust says that the compound's stereochemistry is related to that of dextro oF levo ~ enantiomer of glyceraldehyde. For example, d-fructose is levorotatory. Hence, it is stated that all natural amino acids are L while natural ‘carbohydrates are D. Thus, (+) glucose has the D-configuration and (+) ribose has the L-configuration, Ho Ho ution won Hot HoH HOH cHoH D(+)-alucose Di+)sibose4.8.1 The Gahn Ingold Prelog (CIP) Sequence Rule ‘An absolute configuration refers to the spatial arrangement of the atoms of the chiral ‘molecules and its stereochemical description using terms (R) or (8). Cahn, Ingold and Pretog introduce Sequence Rules to assign an order of priority to the atoms or the groups directly attached to a stereacenter. The absolute configuration of a given stereocenter is defined as either ) o*(S) by applying these rules Rule 1: Atom of higher atomic number is given priority over these of lower atomic number eg. I> 8r>Cl>F>0>N> CoH Rule 2: Isotope of higher atomic weight takes precedence. eg, °H (tritium) > 2H (deuterium) >*H (hydrogen) Rule 3: When two or more atoms directly attached to a stereocenter are same, the order of pricrity depends on the next atom along the chain. eg, ~CO;CHs > -CO,H > CONH, > COCHs > CHO > CH:OH fle fan sts ble boned ott som tes wr Say one tw ftw som, aa sp bogs ater som vents awe diay bord tre of ees tie Cometh ett gp nl Sched ote sere oud doce eo es hie 28 so ey fe BS cece OH mene bP on Apphng owe Sere nls asin te mbes he facta gous pe cea pay e's gnats wens coe ars mee ot Seti ath nes poy soo toe mas ooy ce A cen Sree nd le eein eo ceoSecede eB, Clockwise =(R) 1 Anti-clockwise = (S) ramps 1 2oHo 2 >) ‘As per sequence rule, the order ° As pe sauce we Agno BY) ae ea n7 You ' (r)olyeeraldenyde Clockwise =) (rrraicoraenyae 2 don ‘As per sequence tule, the order wren hy ()Serne (SH-) serine Rule 5: A longer group may not necessarily have a higher priority over another smaller ‘group. e.g. ~CH,CI has a higher priority than ~CH,CH:CH:CH. Rule 6: If a lowest priority group is in the front of the plane of the molecule then the assignment is reversed. ie, clockwise is S and anticlockwise is R.‘ chy ay <- boon ro NG joey oi 2 onan) ON chai = (8) Ibutn ‘Si tomatn Rule 7: If there are multiple chiral carbons in a molecule, the configuration of entire molecule cen be defined by using number that specifies the location of the ‘stereocenter preceding configuration eg, (IR, 45). €g., He, ony HG, cH, 1a ols R ss, st wr] oH 4 Br uZ Ya ‘ec Es af 7 (2R, 3R}-23-citromebutane (28, 38}-2,3eibromobutane _ mese-2,3ibromobutane