UNIT 12 STEREOCHEMISTRY
Syllabus
· Stereoisomerism
· Geometrical and optical isomerism
· Specific rotation
· Chirality, Chiral objects, Chiral molecules
· Configuration and Fischer projections
· Asymmetric carbon
· Elements of symmetry
· Compounds containing one chiral centre
· Enatiomers
· Racemic form
· Racemisation
· Compounds containing two chiral centres
· Diastero isomers
· Meso form
· Resolution
· Importance of stereochemistry
Isomers are different structural arrangements of a molecule constituted from the same atoms. Stereoisomers are the molecules that have the same atomic connectivities but different disposition of atoms or groups in space. Thus in steroisomers , atoms are connected to each other in the same way, but they differ from each other with respect to their relative orientation in three -dimensional space. Stereochemistry is the study of spatial arrangements of atoms in molecules, i.e., how various atoms in a molecule are arranged relative to one another in three-dimensional space.
Stereoisomers are of two types: Conformational and configurational isomers. Conformational isomers differ from each other with respect to the relative positions of some of the atoms in the molecule in three-dimensional space due to rotation about sigma bonds. The inter-conversion of these isomers does not require breaking and re-making of covalent bonds. Configurational stereo isomers on the other hand are due to certain types of rigidity within the molecule, and these isomers can be inter-converted only by breaking and re-making of covalent bonds and not simply by rotation about sigma bonds.
There are two types of configurational isomers, geometrical and optical.
GEOMETRICAL ISOMERISM
Geometrical isomerism is shown by the compounds containing carbon-carbon double bonds. Two carbon atoms linked together by a double bond are incapable of rotation about the bond- axis. Due to restricted rotation of carbon atoms (involved in double bond formation) about the p-bond, the positions of atoms or groups attached to two carbon atoms get fixed and the molecule has a definite orientation of atoms or groups about the double bond. This gives rise to geometrical isomerism.
Geometrical isomerism is shown by the compounds of the type abC = Cab or axC = C ay , where a , b , x and y represent atoms or groups attached to carbon atoms. The compounds of this type may possess different arrangement of
atoms or groups about the double bond and may exist in two forms. In one form , called the cis form or cis-isomer , the similar groups are arranged on the same side of double bond, whereas in the other form called trans form or trans isomer, similar groups get arranged on opposite sides of the double bond as shown below.
Thus geometrical isomerism may be defined as follows.
When two compounds having the same molecular formula, similar chemical structures and a double bond possess different geometrical arrangements of the atoms or groups about the doubly bonded carbon atoms the phenomenon is known as geometrical isomerism and such compounds are called geometrical isomers. The isomer in which the similar groups are arranged on the same side of double bond is called cis- isomer whereas the isomer in which similar groups are arranged on opposite sides of double bond is called trans-isomer. The phenomenon is called cis-trans isomerism.
Geometrical isomers cannot be converted into one another under normal conditions due to the absence of free rotation about the double bond.
Examples of Geometrical isomerism
Some examples of compounds showing geometrical isomerism are given below.
(i) 2-butene (CH3CH=CHCH3)
(ii) 1,2-dibromoethene (CHBr=CHBr)
(iii) 2-butene -1,4-dioic acid (HOOCCH=CHCOOH)
(iv) 2-buteneoic acid (CH3CH=CHCOOH)
Conditions for geometrical isomerism The important properties of geometrical isomers are as follows :
(i) The molecule should must have a double bond.
(ii) The molecule should be of the type either abC=Cab or axC=Cay . Compounds of the type aaC=Cab are unable to exhibit geometrical isomerism. This is because the two possible configuration of such compounds are the same. Thus,
Examples of such compounds are propene and 1-butene. Inspite of the presence of double bond , they are unable to exhibit geometrical isomerism as shown below.
Cause of Geometrical isomerism
The restricted rotation of carbon atoms about a double bond is the main cause of geometrical isomerism. The C=C double bond consists of a sigma(s) and a p-bond. p-bond is formed by the side wise overlapping of unhybridised p-orbitals of the two carbon atoms as shown in Fig.
Formation of a C=C double bond
The carbon atoms involved in double bond formation can not be rotated about the double bond because an attempt to rotate the carbon atoms about the double bond would result in the breaking of p-bond. The breaking of p-bond involves the absorption of 251 kJ mol-1 energy which is not available under normal conditions. Hence the rotation about double bond is restricted or hindered. Due to restricted rotation, the relative spatial positions of atoms or groups attached to carbon atoms involved in double bond formation get fixed. If the groups attached to each of the carbon atoms are different, two different types of spatial arrangement of groups around the double bond as shown in Fig are possible.
(a) (b)
Spatial arrangement of groups around the double bond in (a) cis isomer (b) trans isomer
Fig (a) (above) represents a cis-isomer in which similar groups are arranged on the same side of the double bond whereas, Fig (b) represents a trans-isomer having similar groups arranged on the opposite sides of the double bond. Due to restricted rotation, cis and trans isomers are stable and cannot change into one another under normal conditions.
Properties of Geometrical isomers
The important properties of geometrical isomers are as follows.
i) Geometrical isomers possess different physical properties like melting points, dipole moments , tendency of being adsorbed etc. Therefore , they can be separated by ordinary techniques such as fractional distillation , chromatography etc.
ii) The geometrical isomers have similar but not identical chemical properties.
For example, maleic acid and fumaric acid are geometrical isomers. Maleic acid (cis-isomer) forms an anhydride on heating, whereas fumaric acid (trans-isomer) does not give anhydride on heating.
iii) The stability of two isomers are different. This is because bulky groups present on the same side of double bond in the cis-isomers. This is because bulky groups present on the same side of double bond in the cis-isomer give rise to steric repulsion making it less stable as compared to the trans-isomer.
Geometrical isomerism in Compounds containing C = N and N = N double bonds
Geometrical isomerism is not only restricted to compounds containing carbon-carbon double bonds. Compounds containing carbon-nitrogen and nitrogen-nitrogen double bonds also exhibit this type of isomerism.
The aldoximes and ketoximes contain a carbon-nitrogen double bond and exhibit geometrical isomerism. In aldoximes, the isomer having –H and –OH groups on the same side of C=N bond (analogous to cis-isomer) is referred to as syn , whereas the isomer having –H and –OH groups on the opposite sides of C=N bond (analogous to trans-isomer) are called anti. For example , the geometrical isomers of benzaldoxime are as follows.
Azobenzene contains a nitrogen-nitrogen double bond and shows geometrical isomerism. Its syn and anti forms can be represented as shown below.
PLANE-POLARISED LIGHT AND OPTICAL ACTIVITY
Ordinary light can be considered as electromagnetic wave, which has oscillations in all directions perpendicular to the path of propagation. Under certain conditions, light can be made to have all its oscillations in the same plane and is called plane-polarised light. The plane polarised light can be produced by passing ordinary light through a nicol prism. A nicol prism is made from calcite , a special crystalline form of calcium carbonate.
Fig 1 Change of ordinary light into plane polarised light
There are certain substances which can rotate the path of the plane polarised light either to the left or to the right, when passed through the solutions of these. Such substances capable of rotating the path of the plane polarised light are called optically active substances.
Rotation of the plane of plane polarized light by a solution
The property of an optically active substance as a result of which it rotates the path of the plane polarised light is known as optical activity. The angle of rotation by which the plane-polarised light is rotated can be measured by using an instrument called polarimeter. A schematic diagram of a polarimeter is shown in Fig.
Schematic representation of a polarimeter showing measurement of optical activity.
Unpolarised light emitted by a sodium lamp (the sodium D-line 58.9 nm) passes through a polariser. This plane-polarised light on passing through the polarimeter tube containing an optically active sample emerges with its plane of polarisation rotated from its original position. A second polariser , placed behind the sample, can be rotated by certain angle to compensate for the rotation of plane of the plane-polarised light by optically active sample. If the substance rotates light to the right, i.e., in the clockwise direction, it is called dextrorotatory or the d-form and it is indicated by placing a positive(+) sign before the degrees of rotation. If light is rotated towards left, i.e., in anticlockwise direction, the substance is said to be laevorotatory or ℓ - form and a negative sign(-) sign is placed before the degrees of rotation. Currently, dextro and laevo rotations are represented by algebraic signs of (+) for dextro and (-) for laevo (instead d and ℓ)
The extent of experimentally observed angle of rotation (optical rotation, symbolised as aobs) of a substance depends on the wavelength of light and the number of optically active molecules
in the path of light beam (which depends upon the concentration of the sample and the length of the sample tube). Other factors that influence aobs are the solvent used and the temperature at which the measurement is made. The optical rotation of any optically active compound is expressed in terms of specific rotation [a]
While reporting [a], the wavelength of light used is given as a substript and the temperature (in degrees celsius) as a superscript . It is also customary to designate the solvent and concentration. Thus [a]25D = - 2.25°(c. 0.50 ethanol) means that a was measured at 25°C using sodium D line and the sample concentration was 0.50 g/mL in ethanol.
Problems
1. Calculate the specific rotation of an organic compound if its solution containing 0.75 g / 10 mL and placed in one dm tube gives a rotation of 1.2° at 25°C(D line).
2. (a) Find the observed rotation of a solution of sucrose containing 0.5 g/mL measured in a 5.0 cm tube (D line) if specific rotation of sucrose [a]D is 66.5.
(b) What is the observed rotation if (i) the concentration is doubled (ii) length of the tube is doubled.
MOLECULAR ASYMMETRY , CHIRALITY AND ENANTIOMERS
The foundation for modern stereochemistry was laid when Louis Pasteur 1848 observed that crystals with mirror images of each other exist. He demonstrated that the aqueous solutions of both types of the crystals showed optical rotation, that was equal in magnitude (for solutions of equal concentration) but opposite in direction. Pasteur believed that this difference in optical activity was associated with the three-dimensional arrangement of atoms in the two types of crystals. In 1874 J. van’t Hoff and C. Le Bel independently proposed that all the four valencies of carbon are directed towards the four corners of a regular tetrahedron, and if all the four substituents attached to such a carbon are different, the resulting molecule would lack symmetry. Such molecule is referred to as asymmetric molecule and asymmetry of the molecule is responsible for optical activity in such organic compounds.
The symmetry and asymmetry are also observed in many day-to-day objects. A sphere, a cube and a tetrahedron are identical to their mirror images and thus can be superimposed. Such objects whose projections are superimposable on their mirror images are symmetrical objects. Many objects are , however, non-superimposable on their mirror images. For example, your left hand looks similar to right hand. But if you put your left hand on your right hand, these do not coincide.
Non-superimposable right and left hands
They are non-superimposable mirror images of one another. The general property of handedness is called chirality. Objects which are non-superimposable on their mirror images are said to be chiral, while the objects which are superimposable on their mirror images are achiral.
Let us extend the concept of non-superimposability to organic molecules. Consider 2-chloropropane and 2-chlorobutane and examine them by overlap procedure whether they are chiral or achiral.
The two mirror image forms of 2-chloropropane are A and A1 (Fig).
Fig 4 Projections of 2-chloropropane
Let us reorient A1 to see if it can be superimposed on A. We do it by mentally picking up A1 and rotating it by 180° so that C-Cl bonds in the two images project in the same direction. A2 is obtained by so rotating A1. Now mentally place A2 over A. It is seen that A and A2 are superimposable. Hence 2-chloropropane is achiral.
Consider 2-Chlorobutane. It contains a carbon attached to H, Cl, CH3 and C2H5. The mirror image of B is B1 ( Fig b).
Projections of 2-chlorobutane
Let us reorient B1 to get B2 and find whether it can be superimposed on B. It is noted that B and B2 do not match. The central carbon , the H and Cl atoms can be superimposed but the spatial orientations of CH3 and C2H5 groups are different in B and B2. In B , ethyl group is pointing towards the observer while in B2 , it is pointing away. Thus B and B2 are non-superimposable and 2-chlorobutane is a chiral molecule. The most common indicator of chirality is the presence of a carbon bonded to four different substituents. The molecule CABCD where A, B, C and D are the four different substituents covalently linked to carbon is an asymmetric molecule e.g. lactic acid (Fig). A chiral centre is also known as stereogenic centre.
Non-superimposable mirror images of chiral molecules
If we draw a three dimensional wedge and dash for this molecule and hold it in front of a mirror, we will get mirror image of the molecule as illustrated in the above Fig. These two molecules are stereoisomers.
When a molecule contains one asymmetric carbon, it is always chiral. Common examples of chiral molecules are 2,3-dihydroxypropanal,OHC-CHOH-CH2OH, glyceraldehyde,OHCCH(OH)CH2OH, 2-hydroxypropanoic acid, CH3-CHOH-COOH, lactic acid , bromochloroiodomethane (BrClCHI) etc. These are asymmetric molecules.
The necessary condition for chirality is not just the presence of asymmetric carbon atoms but the asymmetry of the molecule as a whole.
CONDITIONS FOR OPTICAL ACTIVITY OR OPTICAL ISOMERISM
The presence of a chiral centre or stereogenic centre in a given molecule leads to two non-superimposable mirror image structures which are optically active. This is true only in the case of molecules having one such centre. There are certain examples in which molecules with two chiral centres will be optically inactive. Similarly there are certain compounds which are capable of exhibiting optical activity even in absence of any chiral centre or chiral carbon atom.
There are two ways to decide whether a given molecule is optically active or not. Firstly, if a non-superimposable mirror image for a structural formula of the compound can be built, then it is optically active. The second way is to look at certain elements of symmetry.
ELEMENTS OF SYMMETRY
A molecule as a whole is asymmetric if does not possess any elements of symmetry such as : (i) plane of symmetry (ii) centre of symmetry (iii) axis of symmetry and (iv) alternating axis of symmetry.
Plane of symmetry
The plane of symmetry of a molecule represents a plane bisecting the molecule such that each half of the molecule is the mirror image of the other half. The plane of symmetry is called a sigma(s) plane or a mirror plane.
Centre of Symmetry
The centre of symmetry is defined as that point(atom) in a molecule from which if a straight line is drawn from any part of the molecule through that point (atom) and extended to an equal distance by a straight line on the other side, a like point(atom) is encountered. It is symbolised as Ci and is also called the centre of inversion.
Axis of symmetry
The axis of symmetry is an axis through which rotation of the molecule , by certain angle, will result in an arrangement indistinguishable or identical with initial molecule.
Alternating axis of symmetry
The alternating axis of symmetry is an axis through which the molecule is rotated by a certain angle and then reflected across a plane at right angles to the axis, another identical structure is obtained. One fold alternating axis corresponds to plane of symmetry and the two-fold axis to center of symmetry.
Symmetrical objects like books, animals, eggs etc., have a plane of symmetry. sp, sp2 hybridised carbon atoms and sp3 carbons (having at least two identical substituents) too have a plane of symmetry. The sign of swasthika (
) does not have a plane of symmetry but has a center of symmetry. Some of the molecules having a plane of symmetry , center of symmetry or alternating axis of symmetry are shown below:
) does not have a plane of symmetry but has a center of symmetry. Some of the molecules having a plane of symmetry , center of symmetry or alternating axis of symmetry are shown below:
Molecules having two fold alternating axis of symmetry.
a) Line passing through the center, 3,4-dichloro-3,4-dimethylhexane.
b) Same as initial compound
c) Reflection obtained in a plane perpendicular to the line passing through the center.
A molecule with no elements of symmetry of any kind is asymmetric. Objects like hand, tree etc., are asymmetric. A tetrahedral or sp3 hybridised carbon attached to four different groups is asymmetric and is known as asymmetric carbon atom. A molecule with no plane of symmetry is known as dissymmetric. Disymmetric molecules may have an axis of symmetry but the main criterion for dissymmetry is that a given molecule should not be superimposable on its mirror image, Thus all the asymmetric molecules are dissymmetric but all dissymmetric molecules are not necessarily asymmetric. Non-dissymmetric molecules are superimposable upon their mirror images.
An object or a molecule which cannot be superimposed on its mirror image must be asymmetric. Such a pair of molecules related to each other as an object to its mirror image are known as enantiomorphs or enantiomers.
The tems chiral and achiral are also used to designate dissymmetric and non-dissymmetric molecules respectively. A chiral (Cheir meaning hand) molecule is not superimpossable on its mirror image while achiral molecule is superimposable on its mirror image. The chirality of molecules in most cases is due to the presence of a single chiral (asymmetric) atom. A chiral atom is any tetrahedral atom with four different groups attached to it and is also known as chiral center. Enantiomorphs exists only in the case of chiral molecules. Therefore the ultimate test of chirality is that the molecule should be non-superimposable on its mirror image. Thus the molecule will not be chiral if it possesses (a) a plane of symmetry (b) a center of symmetry or (c) an alternating axis of symmetry.
The stereoisomers related to each other as non-superimposable mirror images are called enantiomers. For example, the two structures shown in Fig 6 are enantiomers as they bear non-superimposable mirror image relationship. Enantiomers possess identical physical properties viz., melting point, boiling point, solubility, refractive index etc. They differ only with respect to the sign of the specific rotation. One of the enantiomer will be dextrorotatory while the other laevorotatory. A mixture containing the two enantiomers (dextro and laevo) in equal proportions will have zero optical rotation as the rotation due to one enantiomer cancels the rotation due to the other. Such mixture is known as racemic mixture or racemic modification.
A racemic mixture is represented by prefixing dℓ or (±) before the name, such as (±) butan-2-ol. The process of conversion of an enantiomer into a racemic mixture is known as racemisation.
Problems
03. Which of the following objects are chiral ?
(i) shoe (ii) human body (iii) spoon (iv) screw driver
04. Which of the following molecules are chiral ?
(i) 2,3-pentadiene (ii) 2-hydroxybutanoic acid (iii) s-butyl alcohol
05. Identify chiral and achiral molecules in each of the following pair of compounds.
06. Which of the following are optically active compounds ? Show the chiral carbon with asterisk.
(i) Butan-1-ol (ii) Butan-2-ol (iii) 2-Bromo-2-methylbutane
(iv) 1-chloro-1-phenylpropane (v) 1-Bromo-1-chloroethane
(vi) 2-chloropropanal
ENANTIOMERS
The pair of molecules which are non-superimposable mirror images of each other are known as enantiomers and the phenomenon is known as enantiomerism.
The fact that butan-2-ol molecule and its mirror image cannot be superimposed shows that these are two different molecules. These non-superimposable mirror images are called enantiomers. Thus, the two butan-2-ol molecules are enantiomers. It may be noted that enantiomers must not only be mirror images, they must also be non-superimposable.
Similarly, 2-chlorobutane, lactic acid, 3-methylhexane , etc form non-superimposable mirror images and exist as enantiomers.
Characteristics of Enantiomers
The important properties of the enantiomers are as follows :
(i) Enantiomers are optically active in nature and they rotate the path of the plane polarised light to the same extent but in opposite directions.
(ii) All other physical properties of enantiomers such as melting points, boiling points, density , refractive index, solubility etc are same.
(iii) The enantiomers have identical chemical properties. However, they differ in the rates of reactions towards the optically active substances, but not towards optically inactive substances. For example, (+) lactic acid and (-) lactic acid react with ethanol (optically inactive) at the same rate but they react at different rates with secondary butylalcohol (CH3C*HOHC2H5) which is optically active.
(iv) Enantiomers have different biological properties. For example the sugar (+) glucose plays an important role in animal metabolism and is also the basis of fermentation industry. But (-) glucose is neither metabolised by animals nor fermented by yeasts.
Prochiral carbon and prochiral molecule
A carbon atom is said to be prochiral if the replacement of one of its hydrogen atoms by a substituent atom or group form a chiral centre. The molecule with prochiral carbon is also called prochiral molecule. For example, propanoic acid is prochiral and it leads to enantiomers of lactic acid as follows :
CONFIGURATIONS AND FISCHER PROJECTIONS
The arrangement of atoms that characterizes a particular stereoisomer is called configuration. It is very difficult to draw three dimensional arrangement of atoms or configuration of a molecule on a paper (two dimensional) . Therefore various graphic methods have been proposed. The simplest method is the wedge formula. In this representation, a tetrahedral molecule with four atoms or groups a, b, c and d bonded to it can be represented by wedge formula. A solid wedge (or a heavy line) represents a bond projecting above the plane of the paper(i.e., bonds pointing towards you) and a dashed wedge ( or a dashed line) represents a bond below the plane (i.e., pointing away from you). Solid lines (or continuous lines) represent bonds in the plane of the paper. These representations are shown below :
A simplification of wedge formula is Fischer projection. This method was suggested by Emil Fischer in 1891. He proposed a method for showing the spatial arrangement of groups around a tetrahedral carbon atom on a two dimensional paper. These projection formula for representing especially carbohydrate and amino acid molecules are now used as standard method for depicting sterochemistry.
In Fischer projection, a tetrahedral carbon atom is represented by two crossed lines. The horizontal lines represents bonds coming out of the page(directed towards the viewer) and the vertical lines represent bonds going into the page(away from the viewer). For example the molecule Cabcd may be represented as :
A Fisher projection formula for bromochlorofluoromethane that contains one chiral carbon is shown in Fig (a). For molecules containing several carbons, it is customary to orient the molecule in such a way so that the carbon chain is vertical as illustrated by drawing the Fischer projection formula for glyceraldehyde in Fig (b) from its 3D wedge and dash formula. Although the Fischer projections are planar structures, these can be rotated end-for-end in the plane of the paper only in multiples of 180 degrees , but not 90 degrees at a time. Also Fischer projection formula may not be taken out of the plane of the paper and flipped over.
Representing 3D structural molecules using 2D Fischer projection formula
Problem
07. Draw Fischer projection formulas for following molecules.
ABSOLUTE CONFIGURATION
The three-dimensional structure of a molecule that has one or more centres of chirality is referred to as its absolute configuration. The absolute stereochemistry refers to unambiguous specification of all spatial positions about the centre of chirality. In a compound containing a centre of chirality, there are two stereoisomers. These configurationally different compounds (enantiomers) must be properly designated for their stereochemical identity. Two such conventions for configurational designations are described below.
THE R , S CONVENTION OF CONFIGURATIONAL DESIGNATION
For specifying absolute stereochemistry, a method (accepted by IUPAC) using prefixes R( R stands for rectus i.e., right) and S ( stands for sinister i.e., left) have been developed by R.S Cahn , C.K. Ingold and V.Prelog. The absolute configurations are based on sequence rules. These are briefly discussed as follows :
Step I : The four different atoms or groups attached to the chiral carbon atom are assigned priorities with the help of following sequence rules.
Rule I : Higher priority is assigned to the atom of higher atomic number. For example, the order of priority of H, Cl, Br and I in a descending order is : I > Br > Cl > H.
Rule II : In case isotopes of the same element are attached, the isotope with higher mass number is given priority. For example, deuterium (D) is given higher priority compared with hydrogen (H).
Rule III : In groups, the order of priority or precedence is decided on the basis of atomic number of the first atom of these groups attached to the chiral carbon atom. For example, the order of priority of groups Cl, OH, NH2, CH3 is : Cl > OH >NH2 > CH3.
If the first atoms of two or more groups happen to be same, then the relative priorities may be determined by comparing the second or even third atoms in these groups. For example, in CH3 and C2H5 groups, the first atom carbon is same in both the cases. The next atoms in CH3 group are H, H, H while in C2H5 group are C, H, H. Therefore , C2H5 group has a higher priority than the CH3 group.
Rule IV : If in a group, attached to the chiral carbon, a particular atom is linked by double or triple bond, it is considered to be equivalent to two or three such atoms respectively. If in another group, two or three such atoms are linked separately through single bonds, then the latter will get higher priority. For example,
priority than the the former group.
Step II : When the priorities or preferences of the different atoms or groups attached to the chiral carbon have been decided, the molecule is then oriented in space in such a way that the atom or group of lowest priority is directed away from us. The arrangement of the remaining atoms or groups is then viewed in the order of decreasing priority , i.e., (1) ® (2) ® (3). In doing so, if the eye moves in the clockwise direction, then the optical isomer is assigned configuration R and in case, it is in anticlockwise direction, then the isomer is given configuration S.
Illustration
Designation of R and S configuration employing Cahn-Ingold-Prelog rules
R and S Notations for the optical isomers represented by Fischer Projections
( by planar formulae)
In this case , the step I which decides the priorities of the various atoms or groups remains the same. But step II is different. Four different cases can arise.
Case I : When the atom or group of lowest priority is at the bottom . Simply rotate the eye in the decreasing order of priority and find the configuration of the chiral carbon. For example,
Case II : When the atom or group of lowest priority is at the top. Rotate the entire molecule through an angle of 180° so that the atom or group of lowest priority is at the bottom. For example,
Case III : When the atom or group of lowest priority is on the left hand side. Without changing the position at the top, rotate the molecule in the anti-clockwise direction so that the atom or group of lowest priority comes to the bottom. For example,
Case IV : When the atom or group of lowest priority is on the right hand side of the horizontal line. Without changing the position at the top, rotate the molecule in the clockwise direction so that the atom or group of minimum priority comes to the bottom. For example,
Problems
08. Assign R and S configuration of each of the following :
09. Assign the R and S configuration to the enantiomers of 2-chlorobutane.
THE D, L SYSTEM OF CONFIGURATIONAL DESIGNATION
The notation D and L are absolute stereochemical descriptors that relate substituents disposition at the centre of chirality to that in D- and L-glyceraldehyde.(Relative stereochemistry gives specification of the stereochemical relation between two molecules). The D- and L-nomenclature to glyceraldehyde (2,3-dihydroxypropanal) was arbitrarily given by Fischer who first introduced this system. The stereochemical descriptor D refers to an arrangement about a centre of chirality that is identical to the three-dimensional arrangement in D-(+)- glyceraldehyde in which the –OH group on the chiral centre is on the right in its Fischer projection. Similarly, the other enantiomer of glyceraldehyde, which has –OH group on the chiral centre to the left is given by L configuration (Fig a) .
Three-dimensional and Fischer projections of D- and L-glyceraldehydes.
All the molecules , which could chemically related to D-glyceraldehyde are assigned the D-configuration and those related to L-glyceraldehyde are designated L-configuration as illustrated in Fig (b). It may be noted that there is no direct relation between D,L configurations with d and ℓ or (+) or (-) notations.
Chiral compounds having D and L –configuration relative to glyceraldehyde.
In drawing the Fischer projections while assigning D, L configuration, The Fischer projection of the molecule is drawn in such a way that the main longest chain becomes vertical with carbon-1, the most highly oxidised carbon, at the top. The D,L system is commonly used in assigning stereochemistry to carbohydrates and amino acids. For a-amino acids, the configurational arrangement of –NH2, -COOH, -R and H groups at Ca atom is related to that of –OH, -CHO, -CH2OH and H groups, respectively of glyceraldehyde (2,3-dihydroxypropanal). Thus, (L)-glyceraldehyde, (L)- a-amino acids are said to have the same relative configurations.
Problem
10. Specify the configuration of the following compounds in D or L.
11. Designate the following compounds as R or S :
COMPOUNDS CONTAINING MORE THAN ONE CHIRAL CENTRES- DIASTEREOMERS AND MESO COMPOUNDS
There will be two stereoisomers ( i.e., the R and S enantiomers) for a molecule that contains one centre of chirality. For a molecule containing two chiral centres, we can expect a maximum of four stereoisomers. In general , for a molecule with n chiral centres, there are 2n possible stereoisomers. Let us consider 3-chlorobutan-2-ol, which has two centres of chirality.
Now we write the structures for all the four (22 = 4) stereoisomers of this compound (Fig)
Four stereoisomers of 3-chloro-2-butan-2-ol ; showing enantiomeric and diastereomeric relationships.
Structures II and IV are the mirror images of structures I and III and III and IV are non-superimposable, they are enantiomers. Thus structure I – IV represent the four stereoisomers of compound, 3-chlorobutan-2-ol.
The structures I and III or II and IV are not mirror images of each other. These pairs of stereoisomers are diastereoisomers.
These are the pair of molecules with two or more chiral carbon atoms which are neither identical nor non-superimposable mirror images of each other. However, each one of them is optically active. Diastereoisomers have different physical properties.
A compound with two chiral centres does not always have four stereoisomers. Consider 2,3-dichlorobutane as an example. Now let us write the structural formula of one stereoisomer and its mirror image.
Structures I and II are non-superimposable and thus represent a pair of enantiomers (Fig a). Now we write the structure III and its mirror image IV (fig b).
(a) Enantiomers of 2,3-dichlorobutane.
(b) Achiral 2,3-dichlorobutane
We find that the structures III and IV are superimposable. Thus III and IV represent two different orientations of the same stereoisomer. I, II and III are only isomers of 2,3-dichlorobutane. I and II are optically active while III is optically inactive. The molecules represented by III and IV (Fig b) are achiral even though they contain chiral carbon atoms. Also, the structure III has a plane of symmetry (V). Such stereoisomers as (III and IV) are called meso compounds.
Meso compound has a plane of symmetry which bisects the molecule into two equal and identical halves. When plane polarised light is passed through the aqueous solution of this compound, the rotation due to the upper half cancels with the rotation due to the lower half. As such the compound is optically inactive inspite of the presence of two chiral carbon atoms. This is known as internal compensation since it occurs within the molecule and renders it optically inactive.
Mesotartaric acid is optically inactive inspite of the presence of two chiral carbon atoms. In general , meso isomers may be defined as : the compounds with two or more similar chiral carbon atoms and are optically inactive due to the presence of plane of symmetry.
Characteristics of diastereomers
The important characteristics of diastereomers are as follows :
i) A pair of diastereomers have similar chemical properties since they are members of the same family. Their chemical properties are not identical and they react with a given reagent at different rates.
ii) A pair of diastereomers differ from one another in their physical properties. They have different melting points, boiling points, refractive indices, solubilities and densties etc. They also differ in specific rotation ; they may have the same or opposite sign of rotation.
iii) As a result of their differences in boiling points and in solubility , they can be separated from each other either by fractional distillation or fractional crystallization. Due to their different molecular shapes and polarity , they differ in adsorption, and can be separated by chromatography.
Distinction between diastereomers and enantiomers
Diastereomer | Enantiomer | |
1 | These are stereoisomers that do not have a mirror image relationship. | These are stereoisomers that have a mirror image relationsip. |
2 | These have different physical properties | These have similar physical properties |
3 | These can be separated by physical methods like fractional distillation, fractional crystallization etc. | These cannot be separated by physical methods like fractional distillation, fractional crystallization etc. |
4 | Diasteromers may have rotation in the same direction, but to different extent. They may have rotation in opposite direction in some cases. | Enantiomers have rotation in opposite direction but to the same extent. |
Problem
12. Find out the number of stereoisomers and indicate the relationship between them as enantiomers, diastereoisomers or as meso compounds for the following molecules.
ERYTHRO AND THREO ISOMERS
The prefix Erythro and Threo are used to distinguish enantiomers containing two chiral carbon atoms when two atoms (or groups) attached to each chiral carbon are the same while the third are different. The stereoisomer in which these are present on the same side of the Fischer projection formula , is called erythro isomer while the isomer in which these are present on opposite sides, is known as threo isomer. For example, let us consider the formula CH3C*HOHC*HBrCH3 (3-bromobutan-2-ol). The erythro and threo isomers are represented as follows:
RACEMIC MIXTURE OR RACEMIC MODIFICATION
When two enantiomers of a substance i.e., dextro(+) and laevo (-) are mixed in equal amounts, the resulting mixture will be optically inactive. It is called racemic mixture or racemic modification and this phenomenon is known as racemisation. It is denoted by the prefix (±) or dℓ before the name of the substance. For example, when equal amounts of (+) lactic acid and and (-) lactic acid are mixed, racemic (±) lactic acid is formed.
The racemic mixture is optically inactive because when plane polarised light is passed through solution of racemic mixture, the rotation due to one enantiomer cancels with rotation due to other enantiomer. The path of the plane polarised light remains undeviated. The loss of optical activity in this case is because of external compensation and not of internal compensation which takes place in meso molecules.
RESOLUTION OF RACEMIC MIXTURE
The process of the separation of the racemic mixture into the enantiomers is called resolution. A number of methods can be used to effect the resolution.
1. Mechanical method : This method was introduced by Louis Paster(1848) and is applicable only if the two enantiomers are crystalline in nature and the crystals differ in their shapes. The separation can be effected with the help of magnifying glass and a pair of tweezers. Pasteur separated the enantiomers from racemic sodium ammonium tartrate.
Limitations
(i) The enantiomers must of crystalline nature.
(ii) The crystals must have distinct different shapes.
2. Biological method : In this method certain bacteria, yeast or mould are allowed to grow in a dilute solution of the racemic modification. It consumes one of the enantiomers for its growth , while the other is left behind. For example, when pencillium glaucum is allowed to grow in racemic ammonium tartrate, it consumes (+) ammonium tartrate while (-) ammonium tartrate is obtained as the product.
Limitations
(i) Only one enantiomer is recovered from the racemic mixture, while the other form gets destroyed.
(ii) The yield of the isomer which is recovered is very poor as the micro-organisms can grow only in dilute solutions.
3. Chemical methods : This is probably the best method available for resolution. The racemic mixture is converted into a mixture of two diasteremers by treating with suitable optically active compound. Diastereomers have different melting and boiling points and solubilities. Hence the separation of these diastereomers can be done easily by physical methods such as fractional crystallisation, fractional distillation, chromatography etc. Each diastereomer obtained in this manner is treated with a suitable reagent to give the enantiomer of the original racemic mixture.
4. Chromatographic method : A racemic mixture can also be resolved with the help of column chromatography. The solution of racemic mixture prepared in a suitable solvent is passed through a column packed with a suitable adsorbent. One of the enantiomers is selectively adsorbed on the surface of the adsorbent. It is then eluted suitably and the solution is collected at the bottom of the column is richer in that enantiomer. This results in the separation of the racemic mixture.
CHEMICAL REACTIONS AND STEREOCHEMISTRY
Stereochemical considerations are very important in chemical reactivity. When a chemical reaction involves only achiral reactants, solvents and reagents, the products of the reaction are achiral or racemic mixtures. For example, free-radical monochlorination of n-butane gives achiral 1-chlorobutane and a racemic mixture of 2-chlorobutane.
Enantiomers show equal reactivity towards achiral reagents, but with chiral reagents their reactivity differs. Reactions of the type in which one of the several possible diastereomeric products predominate are called stereoselective reactions. A reaction is stereospecific when a particular stereoisomeric form of the starting material reacts in such a way that it gives a stereoisomeric form of the product. Bromine addition to alkenes is an example of stereospecific reaction. Addition of halogens to alkenes produces diastereomers. Thus, (E)-alkene gives the meso compound while (Z)-alkene gives a racemic mixture. However, if a reaction is carried out using a chiral optically active reagent, only one of the enantiomers or an excess of one enantiomer can be formed. The induction of chirality or asymmetry in this fashion is an interesting feature of such reactions and is referred to asymmetric induction. Asymmetric induction is the use of a chiral reagent or catalyst to convert an achiral reactant to a chiral product having an excess of one of the enantiomers. It is a general principle that optically active products cannot be formed when optically inactive substrates react with optically inactive reagents. Optically inactive starting materials, however, can give optically active products if they are treated with an optically active reagent or if the reaction is catalysed by an optically active substance.
THE IMPORTANCE OF STEREOCHEMISTRY
Stereochemistry is an important aspect of carbon compounds. It is prevalent in the whole of universe. The human body is structurally chiral with heart lying to the left and the liver to the right in the body. Many plants show chirality in the way that they wind around supporting structures. Most of the molecules found in plants and animals are chiral and usually only one form of chiral molecules occur in a species. All but one of the twenty naturally occuuring amino acids that make up proteins have L-configuration. The synthesised D-proteins made from D-amino acids are somewhat resistant to breakdown by protein digesting enzymes because they do not have the chirality to fit in the active sites of these enzymes.
All naturally occuring sugars including the sugars that occur in DNA are of D-configuration. The enzyme, yeast can specifically ferment D-glucose and not its L-enantiomer.
Stereochemistry also plays an important role in deciding the physiological properties of compounds. (-)-Nicotine is much more toxic than(+)-nicotine, (+)-adrinaline is very active in constriction of blood vessels than (-)-adrinaline.
Chirality is crucial for the effect of drugs as well. In a majority of cases, only one enantiomer is found to have the desired effect while the other isomer may be totally inactive or has an opposite effect. For example, the (S)-enantiomer of ibuprofen that has the pain relieving action. (-)-Thyroxin , an amino acid of thyroid gland speeds up metabolic processes and causes nervousness and loss of weight. Its enantiomer, (+)-thyroxine, has none of this effects but is used to lower the cholestrol levels.
Problems
13. Classify the following pairs of compounds as structural , geometrical, conformational or as same compounds :
14. What would be the aobs , if (i) concentration of a sample and (ii) length of the polarimeter tube is doubled ? Will specific rotation also change if the concentration of the sample and length of the polarimeter tube are changed ?
15. Identify and indicate the presence of centre of chirality, if any in the following molecules. How many stereoisomers are possible for those containing chiral centre ?
(i) 2-aminobutane (ii) 1,3-dichloropropane
(iii) 3-bromo-pent-1-ene
16. Draw the wedge and dash formula of the simplest chiral alkane, alkene and akyne.
17. Employing Cahn-Ingold-Prelog rules, indicate priority sequence for : -CH3, -CH2CH3, -CH(CH3)2, -C(CH3)3
18. Assign each of the following compounds an (R) or (S) configuration.
19. Draw three-dimensional representation of (R)- and (S)-2-butanol
20. For each of the following pairs of structures, identify the relation between them. Are they structural isomers, enantiomers or diastereomers ?
21. Which of the following molecules will show optical activity ? Justify your answer.
22. Convert the following :
(i) Wedge–and –dash formula to Fischer projection formula.
(ii) Fischer projection formula to wedge and dash formula.
23. Explain why the following pairs of compounds do not show optical activity ?
24. Draw the structures of optically active unsaturated compound having molecular formula C5H9Br, that after addition of H2 becomes either optically inactive or shows optical activity.
QUESTIONS
1. What is the difference between conformation and configuration in open-chain molecules ?
2. How do structural isomers differ from stereoisomers ?
3. Explain the terms (i) plane polarised light (ii) optical activity (iii) mirror plane (iv) centre of inversion (v) asymmetric molecule (vi) super-imposable mirror images (vii) R and S notations.
4. Point out the difference between (i) aobs and [a]D (ii) Chirality and chiral centre (iii) enantiomers and diastereomers (iv) racemic modification and meso compound.
5. Alkynes do not show any geometrical isomerism. Why ?
6. Write all the isomeric cyclic structures for the molecular formula C7H8.
7. What is the major condition for a compound to be optically active ?
8. In what way does a racemic mixture differ from chiral compound ?
9. Name the alkene with least number of carbon atoms of exhibiting chirality. Draw the structures of possible enantiomers.
10. What is a chiral molecule ?
11. Define specific rotation.
12. Why is a racemic mixture optically inactive ?
13. What happens to a beam of light when it is passed through nicol prism ?
14. Define optical activity.
15. Define asymmetric synthesis.
16. Name one chiral molecule and one achiral molecule.
17. Define diastereomers.
18. Give an example of a molecule having two chiral centres.
19. Write meso form of tartaric acid.
20. Define racemic mixture.
21. What is the essential condition for a compound to be optical active in nature ?
22. How many stereomers are possible for 2,3-dichlorobutane ?
23. Write the formula of D-glyceraldehyde.
24. A carboxylic acid of the formula C3H5O2Br is optically active. What is its structure ?
25. Name a molecule which exhibits enantiomerism but does not contain chiral atom.
26. What is maximum number of stereomers possible for a compound having three chiral centres ?
27. What is the change in specific rotation if the concentration or length of the tube is doubled ?
28. What are enantiomers ? How are they identified ?
29. Explain racemic mixture and resolution of racemic mixture.
30. What are Fischer projections ? Explain with an example.
31. Draw and discuss the stereoisomers of tartaric acid.
32. What is meant by D- and L-configuration ?Explain with one example.
33. Draw the R and S configurations of (i) lactic acid (ii) malic acid
34. Explain the following : (i) diastereomers (ii) mesomers
35. Give examples of chiral and achiral objects.