SMARTER 4 HEMISTRY Inaddition to the methous piv ISOMERISM AND STEREOC! 107 ofthe distances between conay ove MOM C. Others c; *A certain atoms hy "T physical measurements such as the measurement may be of help for deciding the configura OF X-rays, measurement of absorption spectra cte., ation in Some cases, Optical isomerism isa type ot, CPTICAL IsomEnism # ciey have the ably to oa weseteotsamer tun, The outstanding fet activity. Polarized light. This property is « ure of opti cen referred to as opt aac tal Sleettic lami jtispassed through Nicol prismaney only one plane, and! is suid a ee + CaCO) oF polaroid Lense, light is found to vibrate in vibrations of ordinary and po sleet zed or simply polarized, The diagrams illustrate the a . rom 2 beam propagated perpendicularly to the plane of Solutions of some organie « nie com i ; These compounds are said to be out ve the ability to malate the plane of polarized light jing in many different planes, When Activity, ptically Active. This property of a compound is called Optical Optical activity ina compound pound is dk measured by means of a Polarimeter, Whee 4 sation ofa known concentration ofan optically sete ratetil placed in the polarimeter, the beam Grin ight Plane Polarized Light ofpolaized lights rotated troughacenainmumber "S*™Y 8 (Poleised ight) of degrees, either to the tight (clockwise) or to the left (anticlockwise). The Compound which rotates the plane of polarized lightto the right (clockwise) issaid to be Dextrorotatory, Itis indicated by the sign (+). The compound which rotates the plane of polarized light to the left (anticlockwise) is said to Levorotatory. Itis indicated by the sign (~). The magnitude: ‘of the rotation, in degrees, is referred to.as observed rotation, ct. Fig. 4.2 shows the parts of a polarimeter. Nicol Sample solution pais Rotated Ordinary |] Polarized polarized NY & light (Eaaag ight” “ight d 2 QO @® asi Fig. 4.2, A simple polarimeter in operation. Specific Rotation, Optically active compounds rotate the plane of polarized light. The degree of rotation depends upon the number of molecules of the compound encountered by lightalong its path, Lis, therefore, necessary to introduce some standard by which the rotating powers of different ‘compounds may be compared. Specific rotation is defined as the rotation produced by a solution of length 10 centimeters and ‘unit concentration (1 g/ml) for the given wavelength of light at the given temperature, Consider a system in which the plane of polarized light is rotated through 0: degrecs ata temperature of (°C and . if rotniion [Alf in gtven by [oi = LO where ti sing the sodium D-line as thesoures. The specific rotation [a], is given by [o}, = —™ where Lis meters; and isthe umber of grams per 100 of solution. The specific the length: deci length of the tube in deci wavelength of light and the temperature. Folation varies with both the4108 | ADVANCED ORGANIC CHEMISTRY Initial plane of Light polarization ee . Plane polarized light Angle st rotation of 1 Plane polarized ‘ator rotation af plane of polarization “« fant plana of polarization | 4, /> Unpotarired ght Potarizing ier alone filtor sontion of chim substance ’ ito Plann pinlarized EQN pi PLANE OF SYMMETRY sagtrica halves, isa tobe plane of symmetry oy lane which divides an object inta two sym 5 shoes lack a plane ae rug bas a pinne of symm (FB: 4.3)-A pors’s HANH Or OTs °% Plas af ca 4g objet lacking.a plane of symmetry iscalled Dissymmetric pronounced as symmet Ki-ral) Asymmetric object is referred toas Achiral. 1 r 1 ( i t r 1 i i Plane of symmetry Fig. 4.3. Planés of Symmetry. Adissymmetri¢ abject cannot be superimposed on its mirror image, Aleft hand, for example, does not possess a plane of symmetry, and its mirror image is not another left hand but a right hand (Fig. 44), The two are not identical, because they cannot be superimposed. If we were to lay one hand on top of the other, the fingers and the thumbs would clash, Plane of symmetry relationship of the left and right ha ae ‘ @ lett c and Fe that ght hand is the mitror image of the iat hanCHAPTER ob ISOMERISM AND STEREOCHEMISTRY 109, Chiral objets PSYEN Mette Cathe ane den 1 Nang ‘Achiral objects notecule haa a plane of symmetry An a CHIRAL CARBON ATOM A carbon atom which is bonded ta four different groups is called a Chiral (or Asymmetric) Carbon Atom. For example, Chiral carbon, CH,CHs Chir carbon, G0,4 ! I Chee GH GH CH, Hc—oH 1 Br CH,OH ‘The term chiral (Greek handedness; pronounced kalral) carbon atom means th is bonded to four different groups and that a molecule of this type lacks a plane of symmetry. Such Molecule is also called Dissymmetele or Asymmetric. OPTICAL ISOMERISM ‘An optically active compound cun exist in two isomeric forms which rotate the plane-polarized light in opposite directions. These are culled Optleal Isomers and the phenomenon is Known as Optical Isomerism, ‘The isomer which rotates the plane of polarized lightto the right (clockwise direction) is known ag Dextrorotatory Isomer or (+}isomer. The isomer which rotates the plane of polarized light tothe left (anticlockwise direction) is known as the Levorotatory Isomer or (~)-isomet. The optical rotatory Powers of two isomers are equal in magnitude but opposite in sign, An equimolar mixture of the two isomers, therefore, will not rotate the plane of polarized light at all and is said tobe Raceniie Mixture, Optical isomers have the same physical properties melting point, boiling point, density, etc, ‘They have the same specific rotation but with opposite signs.110 | ADVANCED ORGANIC CHEMISTRY MERISM OF LACTIC ACID : ‘ gat aE een eee acidyisan cxample of acompound which shows optical isomerism, Tt contains one chiral carbon atom, mu Lie ai Ton CH= CcooH Eaton i at i Two three dimensional structures are passible for Lactic a bh ch other. One is idemtic ¢ they can not be superimposed on cach of ti ce stnctres are no identical hecause they can not be sup 1 , Faia MeO Suich nonsupe more minor Image forms re optical Somers nda Called Enantiomers Thus three fms of ate acid are knoven Twoare optically activeandthe tg is optically inactive / seucetiretion en |, (Lactic Acid, [rotates the plane of polarized light to the right (clockwise: aris called dextrorotatory. 26 ictic Acid. rotates the plane of polarized light to the left (assent direction) ang iscalled levorotatory, (~}-Lactic acid is the mirror image of (+}-lactic acid and vice versa 3. (}Lactie Actd. Itdoes not rotate the plane of polarized light. Th is optically inactive, ‘TLis an equimolar mixture of (+)-and (—}-forms (racemic mixture), OH y Po ed | Ny H ‘COOH CH : CHs Mircor cooH i COOH Equimotar mixture of i (+) and (-}forms HOEK H—~C—OH (racemic mixture) CH, CHy (+)Acid (hacia (@}-Acid mp = 26°C mp = 26°C mp = 18°C Optically active Fig. 4.5, Isomers of Lactic acid, Structures are shown. In the lower |i given, The vertical lines represent b and horizontal lines represent bon Optically inactive In the upper line two three-dimensional ine a commonly used Fischer projection is onds going away {rom the observor/reader ds Coming toward the observer, CONDITION FOR OPTICAL ISOMERISM The necessary condition for 4 molecule to exhibit Optical isomerism is that it should be 4dissymmetric, That is, the molecule should 1 not be superimposable on its mirror image. In simple molecules, the dissymmetry (also called Chirality) results from the presence ofa chiral carbon s0"- Recall that a chiral carbon is one which is bonded to four differene groups. Consider a chiral molecule Cage, Fig. 4,6shows iva three dimensional models for this molecuCHAPTER 4. ISOMERISM AND STEREOCHEMISTRY | 117 (ph a Fig. 4.6. The two forms (I and Il) of Caggp te nonsuperimposable. ‘The form (II) is the mirror image of (1) and the two cannot be superimposed. IF you try to superimpose the four groups attached toa chiral carbon atom in form (1) and form (Il), only two of the four groups coincide, while the other two are in conflict. This shows that the two forms represent different compounds. ‘The nonsuperimposable mirror image forms of a chiral molecule are called Enantiomers (Greek, enantio = opposite). They represent two optical isomers : (+) and (—). Their opposite rotatary powers are due to the opposite arrangements of groups around the chiral carbon atom. Itis true that most of the compounds which contain chiral carbon atoms show optical isomerism. But it is not always so. There are some compounds (such as meso-tartaric acid) which have chiral carbons but being achiraf, do not show optical isomerism. On the other hand, there are certain compounds (such as substituted allenes and biphenyls) which have no chiral carbons but being dissymmetric, show optical isomerism. OPTICAL ISOMERISM OF TARTARIC ACID Tartaric acid (2,3-Dihydroxybutanedioic acid) contains two chiral carbon atoms. OH H—c* COOH Tartaric acid. The two chiral carbons are H—C*cOOH shown by asterisks. I OH Four forms of tartaric acid are known (Fig. 4.7). Two of them are optically active and two are optically inactive. The optically active forms aze related to each other as an object to its misror image, That is, they are enantionters. ‘Scanned with GamScanner112 | ADVANCED ORGANIC CHEMISTRY Hiro i (OOH coon} Goon & Equimolar mixture of i i —G—OM —“(+}-and (-)forms H-c-on | HO-G-H nr (Racemic mixture wo-¢—4 | Amc =oH H-G-0H coon cooH com tyAdd (ymod I (-)Aeid mena —— mp= 205" mp= 170° f mp = 170°C me 53 aim Optically inactive — Optically inact ee 5. Weomens Tati nc Le} Tartare Actd. Itrotates the plane of polarized light tothe right (clockwise direction) ang is called dextrorotatory. Se di (-}-Tartarie Acid, I rotates the plane of polarized light to the left (anticlockwise direction) and is called levorotatory, (~)-Tartaric acid is the mirror image of (+)-tartaric acid and vicg ws versa, ; 1. meso~ rit | Tepossesses a plane of symmetry and is consequently ‘optically inactive. ; This: ea nee tn is wid to be dnternally compensated (Optical rotation of one chiral carbon is cancelled by that of the other). | 4 (+)-Tartarie Acid. [1 does not rotate the plane of polarized light. That i inactive. [tis an equimolar mixture of (+)- and ()-forms (racemic mixture). TERMS USED TO DESCRIBE OPTICAL ISOMERS Achiral molecule. An achiral molecule is one that can be superimposed over its mirror image; a achiral molecule is identical to its mirror image, Achiral molecules do not rotate plane-polarized light, Chiral center, Typically, for a molecule t be chiral it must have at least one chiral center-9 carbon with four nonequivalent groups. Any molecule that contains a chiral center will be chiral, unless the molecule has.a plane of symmetry, in which case the molecule is achiral (and meso). Chiral molecules, A chiral molecule is one that eannot be superimposed over its mirror image, Chiral molecules rotate pline-polarized light, Diastercomers, Diastereomers are stereoisomers that are not mirror images of each other, For’ molecule to have a diastereomer, il must lypically have more than one chiral center, Enantlomers. Molecules that are mirror images of each other are called enantiomers, Meso compounds, A meso compound is a molecule that contains a chiral center, butis achiral as aresull of having a plane of : ‘symmetry inthe molecule, Optleally active, An optically active compound (such asa pure solution of asingle enantionet ofa molecule) has he ability torotute plane-polarized light, Racemic mixtures, A racemic mixture not rotate plane-polurized |i: ight. PROPERTIES OF ENANTIOMERS ; Optical isomers that are mirror images are called Enantiom: pairs. For example, there are two optical isomers of lactic acid (Fi; ‘Amage of (B). They are 4 pair ofenantiomers, it is opticaly 4s. 450:50 mixture of two enantiomers, Racemic mixtures & ers. These always exist as diserel® ig. 4,8), Notice that (A) is the mito"CHAPTER 4; ISOMERISM AND STEREOCHEMISTRY | 113 Maro coon | COOH Hom GH i Hog OH CHy ' oH “ ' (6) Fig. 4.8. Two isomer of Laetic: ariel Enantiomers are stable, soluble compounds thal dliffer from one another in three-dimensional me arrangements. Enantiomers cannot be intereonverted under ordinary conditions, Enantiomers have identical properties in all reypects except in their interaction with plane of polarized light. Enantiomers have the same melting point, density, solubility, color, and reactivity toward acids and bases. They differ, however, in the direction in which they rotate the plane of polarized light, Both rotate the plane of polarized light to exactly the same extent (same angle) but one rolates the plane to the right (clockwise ; called dextrorotatory), while the other rotates the plane to the left (anticlockwise; called levorotatory), ‘A mixture of equal amounts of two enantiomers is called a Racemic Mixture. Such a mixture is optically inactive (does not rotate the plane of polarized light) because the two components rotate the plane of polarized light equally in opposite directions and cancel one another. PROPERTIES OF DIASTEREOMERS In general, each chiral carbon atom in a molecule doubles the number of theoretically possible isomers. Hence, molecule with » chiral carbon atoms should have 2" stereoisomers. Fig. 4.9 shows the four isomers of 3-bromo-2-butanol, which has rwo chiral carbon atoms. Mirror Mirror CHy GHs Hs 1 GH H-G—OH | HO—¢—H A=t—oH \ Ho-e—H ar—C—H | HG Bo Ager | a cH ft CHs CHy i CHy (A) 1 (8) (©) ‘ (0) Fig. 4.9. Four isomers of 3-Bromo-2-butanol Notice that (A)is the mirror image of (B) ;(C)is the mirror image of (D). Thus the four isomers are (Wo pairs of enantionters, Now compare (A) with (C), They are neither superimposable nor are they mirror images. They are called diastereomers, (A) and (D) are also diastereomers, as are (B) and (C), and (B) and (D). Stereoisomers that are not mirror images of each other are called Dinstereomers. Diastereomers have different properties. Two diastereomers will have different melting boiling points, and solubilities, They will have different chemical reactivities toward! most reagents. PROPERTIES OF MESO COMPOUNDS ; Acompound with two or more chiral carbon atoms but also having a plane of symmetry (a mirror plane) is called the Meso Compound. Fig. 4.10 shows two meso compounds. These molecules have planes of symmetry dividing them midway between the two chiral carbons in each. Notice that one- half of the molecule is the mirror image of the other, Both molecules are optically inactive, even though each has two chiral centers. Neither will rotate the plane polarized light,114 | ADVANCED ORGANIC CHEMISTRY q H gon 40—-6—08 H—C—OH Planeot __ ne | nanan symmetry H,;SC—C—OH H=G-0H 4 GOH 3 meso-2,2-Dihydroxybulane —_moso-Tartaric acid Fig. 4.10, Examples of meso compounds. OPTICAL ACTIVITY WITHOUT ASYMMETRIC CARBONS Compounds containing achiral carbon can exist in optically active forms. However, compoundg Which do not possess a chiral carbon atom can also exist in optically active forms provided that the molecule is dissymmetric, For example, () Allene Derivatives Some derivatives of allene (CHj=C=CH;) exhibit optical isomerism. Example js 1.3-diphenypropadiene. In allenes, the central carbon is sp hybridized, and the terminal carbons are sp” hybridized. The central carbon forms two sp-sp? @ bonds. The central carbon also has two Pp orbitals which are mutually perpendicular. These form x bonds with the p orbitals on the other carbon atoms, As a result, the substituents at one end of the molecule are in a plane which is perpendicular to that of the substituents at the other end, so that the compound exists in two forms which are non- superimposable mirror images and are optically active. Mirror Mirror 4,3-Diphenylprapadiene 2) Biphenyl Derivatives Substituted biphenyls show optical isomerism when substituents in the 2-positions are large enough to prevent rotation about the bond joining the two benzene tings. For example, biphenyl-2,2 disulfonic acid exists in two forms. These two forms are hon-superimposable mirror images, They do not interconvert at room temperature because the energy required to twist one Ting through 180° relative to the other is too high. This in turn is because, during the twisting process, the two-SO3H groups must come into very close proximity when the wo benzene rings become coplanar and strong repulsive forces 2 introduced,CHAPTER 4°; ISOMERISM AND STEREOCHEMISTRY | 115 Mirror SOsH (\-<> SO3H SOzH <>) HO;S Biphenyl-2,2“disulfonic acid (a Biphenyl)ane ; . ON PAPER TIONS : REPRESENTING 3-D STRUCTURES : PROJEC is one chiral center is with Fisch, ving that represents a three, so that (WO substituent, poner en sions & convenient Way OF View ing: molecules with more Ua ischer projection isu conyentent Qvo-dimensionul dr seule, To make a Fischer prajection, you view a chi Y ene » going, back into the plane nt vo thc Pane a YOU (lo hug you), aa two substitucits are gory ba into the plane, out ) SO on Ewe ae shows. Then the chiral center becomes a ciuss an the Fischer projection. Every cross oq ction is achiral center ai ine jist DIE w Ww W why a> fy x 15. Writing @ Fischer projection formula. The horizontal bonds are ming Out of plane of the paper towards you. The vertical bonds are extending into the plane of the paper. {ules for using fischer projections. Fischer projections are convenient for comparing the whemistries of molecules that have many chiral centers, But these projections have their seis of rules and conventions for how you can rotate and move them. The two main ways joule a Fischer projection are as follows : fuel. You can rotate a Fischer projection 180° and retain the stereochemical cos nfiguration, but you cannot rotate a Fischer projection 90°, w x 2. y 180° Rotation’ 5 Y Y Allowed x w Ww Y x ‘\ 90° Rotation Zz Y xP UW x \ A! ¥ Not allowed x z You can rot s ate any three substi ‘substituent fixed and retain the st WwW tuents ona Fischer Projection while holding one lereochemical configuration, Zz Ae > t Y Allowed Y WwOCHEMISTRY 4 IGOMERISM AND STFREOC cuanto 119 LES ASSIGNING CONFIGURATIONS TO CHIRAL MOLECU! ccule is called its absotyy jal molecule ¢ The actual 3-dimensional arrangement af youps in a ell j uystem, The R-S system ig gs Res aystom H configuration. We can specity the configuration hy ists toa neni) called Cahn-Ingold-Pretog system or CH? ayatenn (anied il 7 aha ean in deressing oder chad tothe cl tem, We arrange the four props attached ira carbon with the loves then view the chi priority (1, 2,3. re rules given helow, We then vi fan Gina priorities re priority group (4) on the side opposite the abserver (geomp prioriti “A(N) YA) / \ t v C Y CQ) } (2B ee el So (3) B(2) Anliclockwise As seen by the observer : ; ighest priority (1) ; B has the next highest (2) ; ihe the nen (4). We now go from high to low priority (19233). To . ey i di ind therefore we assign to this structure the $ configuration (S = sinister (1)A Ss A(t) | Inthe above example, A has the: hi and D has the lowest priority an anticlockwise direction, ar =lefi). c 82) oc” NY B(2) ES Clockwiso = R Right tun = As seen by the observer In the structure given above, we go from highest to lowe: direction. We therefore assign to this structure the R configurati To establish the group priorities we use the following Rule 1. Each atom bonded to chiral carbon is assigned a Priority. Priority is based on atomic ‘number; the higher the atomic number, the higher the Priority. Following are several substituents arranged in order of decreasing priority, The atomic number of the atom determining priority is shown in parentheses : priority by moving in a clockwise lon (R = rectus = right). Sequence (63) 65) 17) (16) ay ) (6) a) Highest —!>—Br>—Ci>—sH. —OH > —NH, > —CHg > —H Priority eee Rule 2, For isotopes, forexample, has a higher Lowest Prionty, the higher the atomic mass, the higher the priority. Deuteri Priority than protium (Hyd ea Irogen- 1), WO S705 19 5 Me. 19, Highest > Drei tea > Priority mn (Iydrogen-2) "O> Hs 2H iy - » Lowest ; Priority Rute 3.If priority cannot be assigned on the basiy monly the first atom of a group, then look at the next set signed. Priority is assigned at the first point of diffe of atomic n of atoms Fence, Fol umber oF atom and continue w owing nic Mass considering ntil a priority can be te aseries of proups, arranged120 | ADVANCED ORGANIC CHesusigy inowlerof decreasing priority, Ay 5a i bad Shown is the atomic numberof the atom on which the assigning um ww 7 ay a” (6) @ a HCI = CHOW s —CHLNH, » —CHCHy > —CH2D > —CHeH > Prony oMy CH oye > CHy—CH— > CH\CH,— > CHy— < chy ony : 7 Rule 4. Inthe case of double and Uriple bonds, atoms participating in the double or triple bond are svasidered fo be bonded to an equivalent number of similar atoms by single bonds, that is, atom op doable and triple bonds are replated, Forexample, HOH BNomech yd! wees Boe a fg oC c-c ci > -ets = td oh cc CH CH ©- >HOEC— >CHy—G— > CH=CH > CHy—CH > CHyCH CHa Lowes Pry The R and S notations can be used as part of the IUPAC name of an asymmetric molecule © Provide a complete structural description, including configuration. The (R) and (S) designations Prevede the remainder of the name, separated from it with a hyphen. Ready reference. The priority sequence for the most common groups and atoms is given below ql (High Priority) —1, —er, —Cl, —SH, —F, -O—C—R, —or, —OH, —NOz, 9 9 ll ll I ql TNH-C—R, —NRa, —NHR, —NH2, —CCl, —C—Cl, —C—or, —C—OH. 9 ° I ll {I TC=NHp, —C—R, —C—H, —CN, —CHOH, CéHs—, —CR, —CHR,, —CHsB —CHs, —D, —H (Low Priority) Ordinarily you are given a Fischer projection formula and asked to specify configurationby R Snotation. Iti easy to do so if you follow the following step-by-step method. Consider the follovilS ampleHis, | CHAPTER. 4. gonERIgM AND STEREOCHEMISTRY | 494 )CHy ie a“ B-—Brn cl cia) Order of Priority () Q) @ (4) H (atomic number 1) (Lowest) Step 1. Determine the priority of groups attached to the chiral carbon ator. Apply the sequence rules carefully. In the above example, the order of priority #6 Br 5 Cl > CH, > H step2. Position the lowest priority group (inthis case H) down and away from the observer. This is done by interchanging groups bonded to the asymmetric carbon. Remember that interchanging any pair of groups in a Fischer projection inverts the configuration. Interchanging two pairs of groups retains the original eonfiguration. Thus, theinterchange operation must always be done in pairs or twice chiral to avaid a configuration change. Inthe above example, a dotted line has been used to highlight a bond between the asymmetric carbon and the lowest priority group (H). The interchange operations have been shown by double-headed curved arrows. Step3. Specify the direction of decreasing priority of the three groups (1-22-93). Ignore the lowe: priority group. Ifthe groups 1,2, and 3 arearranged in clockwise fashion, the configuration is R. If the groups occur in anticlockwise fashion, the configuration is S. Inthe above example, the configuration is S because the groups 1, 2, and 3 are arranged in anticlockwise fashion (shown by circular arc). The configuration of compounds with more than one chiral center can also be specified by the R-S system, The configuration of each chiral carbons determined individually, using the same rules as for compounds with one chiral center. The configuration of afl chiral centers dre then specified before the name of the compound, identifying each chiral carbon by a number before the symbol Ror S. For example, 1CHO Both C-2 and ‘lon C3 are chiral i CH.OH Configuration for carbon 2: (0. OH OHM HON, oe H—¢—OH HOCH, —GH—_G}- CHOW) ci @ CHOH Hm 1 CH,OH Scanned with CamScanneeCHAPTER 4 ISOMERISM AND STEREOCHEMISTRY | 494 CH, fee 4) H—-C— ) H—G—Br(t) mm coon gas S conliguration ci) rn fanticloekwise) Order of Priority (1) Br(atomic number 79,9) (Highest) @_Cl(atomic number 35.5) Q) CH; (C. atomic number 12) (@)_H (atomic number 1) (Lowes) Step 1. ee eee of groups attached to the chiral carbon atom. Apply the sequence rules carefully. In the above example, the order of priority is : Br Cl 5 CHy > H Step2._ Position the lowest priority group (in this case H) down and away from the observer. Thisis done by interchanging groups bonded to the asymmetric carbon Remember that interchanging any pair of groups ina Fischer projection inverts the configuration. Interchanging two pairs of groups retains the original configuration. Thus, theinterchange operation must always be done in pairs or twice chiral to avoid a configuration change. Inthe above example, a dotted lin has been used to highlight a bond between the asymmetric ighlig carbon and the lowest priority group (H). The interchange operations have been shown by double-headed curved arrows. Step3. Specify the direction of decreasing priority of the three groups (1-223). Tenors the lowest priority group. Ifthe groups 1,2, and 3 are arranged in clockwise fashion, the configuration is R. If the groups occur in anticlockwise fashion, the configuration is S. In the above example, the configuration is $ because the groups 1, 2, and 3 are arranged in anticlockwise fashion (shown by circular arc). ‘The configuration of compounds with more than one chiral center can also be specified by the R-S system. The configuration of each chiral carbon i determined individually, using the same rules 1s for compounds with one chiral center. The configuration of afl chiral centers are then specified before the name of the compound, identifying cach chiral nrbon by a number before the symbol R or S.Forexample, 1CHO eS HOH Both o-2 and C3 are chiral pepe 4 CH,OH Configuration for carbon 2: CHO. HH OHM ts oO ipsa H—-G—OH = HOCH, —GH-EG}-CHO) 1 ® \bhon Ha) I CH,OH Seanned with CamScanner2 ADVANCED ORGANIC CHEMISTRY Onder of priority ts oH —OH > —CHO > —CH—CH,OH > =H Conhpuravon al 266 (22) Configuration for carbon 3: CHO CHOW rey H—C—OH = @)HOHC | CH,OH Order of priority is : in —OH > —CH-CHO > —CH,0H > —H Configuration at C-3 is (GR) compound is therefore (2R,3R)-2,3,4-trihydroxybutanal. Note that The name of the above und two chiral centers in one molecule. jentheses refer to the configurations aro\Resolution of Racemic Mixture Pure enantiomers of optically active compounds are often obtained by isolation from biological sources. Most optically active molecules are found as only one enantiomer in living organisms, For example, pure (+) -tartaric acid can be isolated from the precipitate formed by yeast during the fermentation of ethyl alcohol. When a chiral compound is synthesized from achiral reagents, a racemic mixture of enantiomers is obtained. For example, reduction of 2-butanone (an achiral compound), gives a racemic mixture of 2-butanol (a chiral compound). °o Hy 1H, I Hy Pt CH3— C —CH,—CH, —* OH + HO. H 2-butanone CH,CH, CH,CH, Racemic mixture of 2-butanol A pure enantiomer of 2-butanol, is obtained by ing i " i tanol, separating it from the other enantiomer. The separation of enantiomers from a racemic mixture is called resolution of racenric mixttre. Resolution of racemic mixture is not Possible by usual physical separation techniques. Following special methods have bee i enantiomers from a racemic mixture. ™ used for the separation of (a) Mechanical method: In 1848, Louis Pasteur noticed that racemi ic aci ee ; tarta id crystallizes into two types of crystals which are mizzor images OE ac sites ie mechanically separated the two types of crystals using a microscope and a pair of tweezers. He found that solutions made from the left-handed, crystals rotated the plane SSuuinensauy oe of polarized light in one direction, and sol rotated polarized light in the opposite direct crystallize a8 separate enantiomers. 01 of racemic mixtures, This mechanic; important, {b) Biological method: This method makes one of the two enantiomers, consume it, le example, Pemieilfinm sheucuan destrays (¥)-1 unaffected. Thus racemic mixture of tartirie (tartaric acid és obtained! at method is also not vory satisfactory, ns made from the right-handed crystals Unfortunately, few racemic compounds methods are, therefore, required for resolution ‘al method of resolution is, however, historically ¢ Of, special types of bacteria which attack ing, Wehind the other, unaffected, For ic acid and leaves the (-)-tartaric acid cld can be resalved! by this method. Since ost of (4) ~tarlaric acid, which is destroyed, biological (¢ Chemical method: The most common method for resolving a racemic mixture into its enantiomers is to use a pure enantiomer, called the resolving agent that reacts with the compound to be resolved, When the two enantiomers of the racemic mixture react with the pure enantiomeric resolving agent a pair of diastereomers is obtained, The diastereomers are separated easily by fractional crystallization, and then the resolving, agent is removed from the separated enantiomers. To illustrate we take the example of (2) -tartaric acid. To resolve this acid we need a naturally pure base, The alkaloid bases commonly used for this purpose are (-)-brucine and (-) cinchonine, On treatment with (-)-base, (+)-tartaric acid gives a mixture of two diastereomeric salts: (+)-tartarate of (-)-base and (-)-tartarate of (-)-base, These diastereomeric salts have different solubilities and can be separated by fractional crystallization. After the separation and purification of diastereomeric salts, each is treated with dilute sulphurie acid which decomposes the salt into the (+)- and (-)-tartaric acid. The base remains in solution as its soluble sulphate. The same procedure may be adopted for the resolution of a (+)-base with an optically active acid like (-)-malic acid. (4) base | eacid = 9 (4) = (-) salt oe (4) tae (base on racemic mixture 1 (-)- {-) salt ——> (-) base + diastereomers fractionally crystalizable Aracemic alcohol is resolved as follows: (+) -alcohol ()-aleoho! racemic mixture fe epeacid 0) =) ester (9) alec OH’ L__5 (-)- (-) ester —> (-} -alcohol * diastereoisomers The chemical method of resolution is widely used and ioe cyanea ha both the enantiomers are obtained. ‘Compounds other sn se ines me nd alcohols can also; be resolved. Although the particular cl emistry may Principle remains the same:we! 1 (d) Chromatographic method: More recently chromatographic method has been used for the resolution of racemic mixtures. The basis of chromatographic separation of a racemic mixture involves passing the mixture through a column consisting of a chiral substance. The two enantiomers move along the column at different speeds, because of their different interaction with the active material of the column, and hence are separated, This has been successfully accomplished with paper, column, thin layer, and gas liquid chromatography. For example racemic mandelic acid has been almost completely resolved by column chromatography on a starch column.