UNIT I AROMATICITY Localized and delocalized bond: If the bonding electrons shared by only two atoms, then the

bond is known as localized bond and the electrons are known as localized electrons. If the bonding electrons shared by more than two atoms, then bond is called delocalized bond and the electrons are called delocalized electrons. Delocalization of electrons causes the extra stability to the molecule by means of resonance. For example, all the six carbon atoms in benzene has one p orbital, the side over-lap causes the alternative double bonds. The double bonds are separated by a single bond then it is called conjugation. Conjugation relies on the partial overlap of p-orbitals on adjacent double or triple bonds. A common conjugated system involves 1,3dienes, such as 1,3-butadiene

in a conjugated system, overlap of p orbitals allows electrons to be delocalized over a larger portion of the molecule, thus lowering the energy of the molecule and making it more stable However, it is possible for two systems to be in cross-conjugation with each other, as in the example below (the two benzene rings are crossconjugated, NOT conjugated

Hyperconjugation The ability of the -bond electrons of an -C H bond to undergo conjugation with the adjacent -electrons is called hyperconjugation.

The ortho-and para-directing effect of methyl group in toluene is attributed to electron release by hyperconjugation. Aromaticity The name aromatic was originated from the characteristic odor or aroma of benzene-like compounds, chemists now have a completely different method of deciding whether a compound is aromatic or not. Based on the analysis of a number of compounds with unusual resonance stabilization energies, the following characteristics have been accepted as criteria for aromaticity.

1. The structure must be cyclic. 2. The ring must be planar. 3. Each of the rings must be SP2 hybridized (or occasionally SP hybridized) and have an unhybridized p-orbital. 4. The total number of electrons in the molecule or ion should be (4n +2) where N=0,1,2,3,...... 5. The unhybridized p-orbital must overlap to give a continuous ring of parallel orbital (the condition of planarity is for effective overlap). 6. This delocalization of electrons over the ring result in the lowering of the electronic energy Let us see some examples 1. Cycloheptatriene: Cycloheptatriene is not aromatic. Even it obeys the huckel rule(6 electrons where n=1) but the presence of sp3 hybridised carbon, the electrons circulation is not continuous

2. Cyclooctatetraene It is a non-aromatic. The non-aromatic character as it does not obey the Huckels rule. Molecules do not possess a closed shell planar configuration in the ground state. This is the reason for the instability or reactivity of these compounds. Monocyclic (4n) electrons molecules are less stable than acyclic. This decreased stability of 4n molecules has been attributed to antiaromaticity.

The metal acts as an electronic source, supplying two electrons to the cyclooctatetraene. The resulting dianion has ten electrons (a Huckels number) and by planar configuration becomes aromatic and therefore, more stable.

Heterocyclic compounds Heterocyclic compounds can also be aromatic since for the application of Huckels rule what one needs is a ring of atoms, all with unhybridized p orbital in a planar arrangement in order that the p orbital overlaps in a continuous ring. Thus the heterocyclic compounds are all aromatic.

Pyridine Both benzene and pyridine have a similar Kekule structure. Pyridine with resonance energy of 27KCal (113KJ ) per mole shows typical characters of aromatic compound. The nitrogen atom in pyridine is SP2 hybridized nitrogen donates one electron to the system and this along with one each from the five carbon atoms give pyridine a sextet of electrons similar to that in benzene.

The non-bonding electrons of nitrogen are in an SP2 orbital which lies in the plane of the ring and these electrons do not interact with the system of the ring. The unshared pair of non-bonding electrons confers on pyridine the properties of a weak base. Thus pyridine protonates to yield the pyridinium ion which retains its aromatic character since the process does not disturb the electrons of the aromatic sextet. Pyrrole, furan and thiophene in fact represent 1-hetero 2, 4-cyclopentadiene and a butadiene unit bridged by a hetero atom bearing lone pairs. In electronic structure these three compounds are similar to cyclopentadienyl anion.

Pyrrole In pyrrole only four electrons are contributed by the carbon atoms of the ring. To make an aromatic sextet the SP2 hybridized nitrogen then contributes two electrons. Pyrrole is far less basic than pyridine because these apparently unshared electrons are in the aromatic cloud. These are not readily available for bonding with proton (protonation). Furan and thiophene Both furan and thiophene have two pairs of electrons on the hetero atoms and therefore, combine the structural features of pyrrole and pyridine. One pair of electrons is in the sixelectron system and other lies in the plane of the ring. Annulenes Conjugated monocyclic polyenes, CnHn in which n =10 are usually called annulenes, The annulenes have n= 10, 12, 14, 16, 18, 20, 24, 30. Out of these only[10], [14], [18], [30] annulenes are (4n +2) electrons molecules, whereas the rest are 4n molecules. The criteria for aromaticity applied to higher annulenes as well. [10]-annulene can be

In [10]-annulene, there is considerable steric interaction between hydrogens at 1 and 6 positions. Further, a planar form (regular decagon) requires an angle of 144 between carbon atoms which is too large to accommodate in a sp2 framework. The system prefers a nonplanar conformation and is not aromatic. But Bridging C1 and C6 in [10]-annulene leads to the compound
o

VII which is reasonably planar with all the bond distances in the range of 1.37-1.42A and show aromaticity.
o

[14]-annulene Bond lengths in [14]-annulene range from 1.35-1.41A but do not show the alternating pattern of localized polyenes. It is aromatic (except for the isomers that are not planar). NMR shows that it is in conformational equilibrium as shown below.
o

The steric interactions associated with internal hydrogens can be minimized if C3, C6, C10 and C13 positions are locked using suitable bridging units. Thus trans-15,16-dimethyldihydropyrene and its diethyl and dipropyl homologs are aromatic with C-C bond distances between 1.39-1.40 A . Conformational flexibility in [14]-annulene can be restricted by inserting triple bond in place of one of the more double bonds. Here, the triple bond contributes only two electrons for delocalization leaving the other two localized. [18]-annulene The cavity in [18]-annulene is sufficiently large and hence the steric interaction involving internal hydrogens is at minimum. The molecule is free of any significant angle strain, nearly planar, and show aromaticity. Its estimated resonance energy is 37 kcal/mol, which is in the range as that of benzene.
o

The planarity and extent of delocalization in [18]-annulene can be improved by constructing its periphery around a saturated core as in following Figure

This compound shows significantly improved delocalization and aromaticity (2 times) compared to [18]-annulene Homoaromaticity If a stabilized cyclic conjugated system (4n+2) electrons can be formed by bypassing one saturated atom, that lead to homoaromaticity. Compared to true aromatic systems, the net stabilization here may be low due to poorer overlap of orbitals. Cyclooctatrienyl cation (homotropylium ion) formed when cyclooctatetraene is dissolved in concentrated sulfuric acid is the best example to demonstrate homoaromaticity. Here, six electrons are spread over seven carbon atoms as in Tropylium cation. Electron delocalization in this case is pictorially represented below

Azulenes Azulene is one of the few completely conjugated non-benzenoid

hydrocarbons that appear to have appreciable aromatic stabilization. Azulene may be regarded as a combination of aromatic cyclopentadienyl anion and aromatic cycloheptatrienyl cation. The structure of azulene itself has been determined by both X-ray and electron-diffraction measurements. The peripheral bond lengths are in the aromatic range and show no regular alteration. The bond shared by the two rings is significantly longer, indicating dominant single-bond character.

ANTIAROMATIC A conjugated cyclic system with 4n electrons is called anti aromatic since in it electron delocalization results in increase in energy (destabilization).

Cyclobutadiene is thus an antiaromatic compound. Since the delocalization of the electrons results in an increase in the electronic energy. Cyclobutadiene is less stable than its open chain counterpart (1, 3, butadiene).

Cyclobutadienyl dication 2 electrons (4n+2; n = 0); the delocalization of 2 electrons is possible through the empty p orbitals hence Aromatic.

Fullerenes These are an exciting new classification of aromatic organic molecules that consist of pure carbon. The formula for Fullerenes are either C60 or C70. The shape of these remarkable allotropic forms of pure carbon are shaped like soccer balls or icosahedrons. They are also called Buckministerfullerenes named after an architect, Buckminister Fuller, who developed the geodesic dome like structures as a viable architectural structure. This structure is a network of hexagons and pentagon. Regardless of the number of carbon atoms in the Fullerene molecule, there must always be 12 five membered faces with a varied number of six membered faces. Each carbon atom in the molecule is sp2 hybridized. Since each carbon has four valence electrons, three of them are in the three sp2 hybrid orbitals with the fourth electron in the unhybridized "p" orbital and delocalized. The Fullerenes possess facinating

properties because of their unusually high electron affinity. They readily accept electrons from metals such as Potassium to form fulleride salts like K3C60. These salts have the Potassium cations attached to the exterior of the Buckey Balls, but recent research has shown that the metal cations can be encapsulated within the geodesic structure. Apparently, these salts become superconductors below 18 Kelvin.

Tautomerism Tautomerism refers to the dynamic equilibrium between two compounds with same molecular formula. It is also called as desmotropism or kryptotropism or prototropy or allelotropism. It is most often a special case of functional group isomerism. In general, the tautomers have different functional groups and exist in dynamic equilibrium with each other due to a rapid interconversion from one form to another. It is very important to note that the tautomers are not the resonance structures of same compound. 1) Keto-enol tautomerism: The carbonyl compounds containing at least one -hydrogen atom exhibit keto-enol tautomerism. The carbonyl group can be converted to enol form due to transfer of one of the -hydrogen onto the oxygen atom. The % composition of keto enol tautomeric mixture depends on the relative stabilities of these two forms. In general the keto form is the low energy form and is more stable than the enol form. However the enol form is also stable in certain cases due to other stability factors. The dynamic equilibrium between a keto form and an enol form exhibited by acetone is shown below. The tautomers are formed due to complete transfer

of hydrogen. However the relatively stable keto form exists in higher percentage (about 99%).

However enol form is also appreciably stable in case of 1,3-dicarbonyl compounds like acetoacetic ester (ethyl aceto acetic ester) as depicted below.

The enol form is more stable than the keto form in case of phenols due to resonance stabilization of aromatic ring.

2) The nitro-aci tautomerism: It is exhibited by nitro compounds containing atleast one -hydrogen. In this case also, the hydrogen atom is transferred completely from one atom to another during the conversion of nitro form to aci form and vice versa. E.g. The nitro-aci tautomerism exhibited by nitromethane is shown below.

Nitroso-Oxime Tautomerism

This equilibrium lies far to the right, and as a rule nitroso compounds arestable only when there is no -hydrogen.

Imine-enamine Tautomerism

Enamines are normally stable only when there is no hydrogen on the nitrogen (such as R2C = CR NR2). Otherwise, the imine from predominates.

UNIT IV CONFORMATIONAL ANALYSIS The rotational symmetry of a bond (a carboncarbon single bond) allows the atoms or groups of atoms connected rotate about it. As a result of this kind of rotation, many molecules assume several different three-dimensional shapes. Chemists call these different shapes conformations. Some conformations of a particular molecule are more stable than others are. Knowing this will help you understand how many chemical reactions proceed. Conformational analysis is the examination of the positions a molecule takes and the energy changes it undergoes as it converts among its different conformations. Because each of the various conformations of a molecule has different properties, the conformation the molecule normally adopts has a profound influence on its physical and chemical properties. Organic chemists use conformational analysis to understand the behavior of molecules in chemical reactions. Biochemists and molecular biologists also use conformational analysis to study the ways molecules interact with each other in living systems. CONFORMATIONS OF ETHANE Consider the ethane molecule, CH3-CH3 and imagine that one methyl group is rotated about C-C bond as axis with other methyl group at rest. The following diagram represents the change in potential energy of thane in the course of one complete rotation about C-C bond. Potential energy is plotted on Y-axis and the angle of torsion (or dihedral angle) ( ) is plotted on X axis.

In the case of ethane, there are six conformations three are called eclipsed conformations (Ia, Ib and Ic) corresponding to energy maxima for which 0, 120 or 240 and other three called staggered conformations (IIa,IIb and IIc) which correspond to energy minima for which 60, 180 and 300. These conformations are represented in saw-horse and Newman projections

The energy profile diagram shows that the Ethane exists in 6 conformations. Three of which are staggered conformations and the three eclipsed conformations and all energy minimia (stable conformers) and maxima (unstable) are identical. Among the various conformations of ethane, the one with the least energy is the most stable. The energy profile diagram indicates that the staggered conformations are 2.9 kcal/mole lower in energy than the eclipsed conformations. A staggered conformation of ethane is more stable than an eclipsed conformation because the staggered conformation maximizes the separation of the electron pairs in the molecular orbitals of the CH bonds. In the eclipsed conformation, the hydrogens are closer; thus, the repulsions of the electron pairs are greater. Chemists call this increase of energy associated with eclipsed bonds on adjacent atoms torsional strain. Following Figure illustrates the change in distance between the CH bonds in the staggered and eclipsed conformations of ethane.

Conformations of Butane: For the conformational analysis of the butane, Butane is considered as derivate of ethane i.e the two CH3 groups as substituent on the each carbon atom of ethane respectively. Consider only the conformations related to the rotation about the C2C3 bond.

The

structure

of

butane

has

two

distinctly

different

staggered

conformations. In one, the two methyl groups have a gauche conformation. In the other, the two methyl groups have an anti conformation. In the gauche conformation, the torsional angle between the two methyl groups is 60o. For the anti conformation, the two methyl groups have a torsional angle of 180o

The anti and gauche conformations of butane have an energy difference of 0.8 kcal/mole. The anti conformation is more stable than the gauche conformation because the two methyl groups are farther apart in the anti conformation. Thus, the anti conformation has less van-der Waals strain than the gauche conformation. The van-der Waals radius of a hydrogen atom is 120 pm, and that of a methyl group is 200 pmnearly twice as large as a hydrogen. Because the methyl groups of butane are closer in the gauche conformation than they are in the anti, the compound has greater van-der Waals strain in the gauche conformation.

Similarly Butane has two distinct eclipsed conformations about its C2C3 bond. In one, the two methyl groups eclipse each other. In the second, each methyl group eclipses with a hydrogen atom. Both conformations have the same number of eclipsed bonds and the same amount of torsional strain. However, the methylmethyl eclipsed conformation has significantly more van-der Waals strain than does the methylhydrogen eclipsed conformation. The greater strain arises from the larger methyl groups that take up more space, and thus have more electron repulsion, than the hydrogens.

Following Figure shows the energy diagram for the different conformations of butane. As in the case of ethane, the staggered conformations of butane are more stable than the eclipsed ones.

From the energy profile diagram, it is observed that the staggered conformations and of butane does not have the same energy level, and all the eclipsed conformations does not have the same energy level. The conformation with the greatest energy is the one with the methyl groups eclipsed; the conformation with the least energy is the one with the methyl groups anti. The energy difference of 6.1 kcal/mole between that maximum and minimum is the energy barrier for rotation about the C2C3 bond in butane. It is higher than the 2.9 kcal/mole rotational energy of ethane because of the addition of the van der Waals strain to the torsional strain. Although rotation about the C2C3 bond of butane is still a rapid process, it is much slower than the rotation about the CC bond in ethane.

CONFORMATIONS OF 1,2DIHALOGENOETHANES In gaseous state at 22 C,1,2-dichloro and 1,2-dibromoethane exist predominantly in anti conformation (Ia) (73% and 83%) like n-butane (67%). However, the greater stability of anti form (Ia) in case of 1, 2 dihalogenoethanes compared with n-butane is due to the combined electronic (dipole-dipole) and steric effects. In polar solvents and in liquid state the dipole-dipole repulsion decreases due to high dielectric constant of the solvent and the proportion of the gauche conformations (Ib & Ic) increases

Conformation of 1,2-dihalogenoethanes As the number of halogen substituents increases as in 1,1,2,2-

tetrahalogenoethenes, the gauche conformations (IIIb & IIIc) become stabe forms over anti (IIIa) which is attributed to the widening of X-C-X bond and stablies the gauche over anti Conformation of polyhalogenoalkanes

Conformations of 1,2 diol:

CONFORMATIONS OF CYCLOHEXANE Through a process called ring inversion, or chair-boat-chair interconversion, one chair form of cyclohexane converts to another chair form of cyclohexane. That is, the back rotates down to become the footrest and the footrest opposite it on the ring rotates up to become the back.

Rotate C1, the back, down; then rotate C4, the footrest opposite it, up. In this process of ring flipping, the equatorial substituents become axial, and the axial substituents become equatorial. Also, all carbons in the back position move down to the footrest position, and all carbons that were in the footrest position move up to the back position. As you can see, when you rotate one of the CC bonds in the ring, that rotation affects the relative positions of all the constituent atoms of that molecule. The process of ring inversion takes cyclohexane through a conformation called the half-chair conformation. The half-chair conformation exists at the point in the inversion process when the footrest carbon, C4, has rotated up to form a plane with carbons C2, C3, C5, and C6.

The position of C1, the back of the chair, is still, at this point, unchanged. This conformation is the transitional state between the chair and the twist boat forms. At room temperature, this process of inversion goes on constantly. The halflife of a particular chair conformation of cyclohexane is approximately 105 seconds. That is, every 105 seconds half of the molecules in a given sample of cyclohexane undergo a ring flip. The energy diagram illustrates each step of ring flipping from one chair form to the other chair form and shows the variation in energy that accompanies the ring inversion.

Conformational Analysis of Monosubstituted Cyclohexanes The ring inversion, or ring flipping, that occurs in a molecule of cyclohexane takes place between two equivalent conformations. Thus, when a cyclohexane molecule flips between chair forms, the energy level for both forms is the same. However, if there is a substituent on the ring, the

number of molecules in each conformation is different because the conformations are no longer equivalent. For example, if a hydrogen of cyclohexane is replaced with a methyl group to form methylcyclohexane, the two chair forms are different. In one the methyl group is equatorial, and in the other, it is axial.

The two chair forms are not present in equal amounts. Experimental evidence shows that at room temperature approximately 95% of the methyl groups are equatorial. This can be explained as follows: Methylcyclohexane has the methyl group in an axial position on C1. As you see, an axial methyl group is quite close to the axial hydrogens on C3 and C5. When they are at their closest position, the hydrogens on the methyl group are less than 200 pm away from these axial hydrogens. Following Figure illustrates the structure of methylcyclohexane.

This distance is less than the sum of the van der Waals radii for two hydrogens (240 pm), so the axial conformation of methylcyclohexane is destabilized by the strain of the van der Waals repulsive forces. The van der Waals repulsive forces arise when the electron clouds surrounding the atoms get close enough to repel one another. This is called 1,3- diaxial interactions. Now rotate the methyl group to the equatorial position. Here all the hydrogens are in the axial positions, and the distance between them is about 400 pm, much greater than the combined van der Waals radii. The stability of cyclohexanes having other axial substituents depends on the size of the substituent. For example, for fluorocyclohexane, about 40% of the molecules have fluorine in the axial position. When the substituent is an isopropyl group, about 3% of the molecules have the substituent in the axial position. Conformational Analysis of Disubstituted Cyclohexanes Consider a cyclohexane ring bears two substituents, the substituents are on the same side of the ringone in the equatorial position and the other in the axial position.

Because both substituents are on the same side of the ring, they are cis to each other. Flip molecular model of cis-1,2-dimethylcyclohexane into the other chair conformation. Note that the methyl group on C1 is now in the axial position, and the methyl group on C2 is in the equatorial position (e,a or a,e)

Now take the other molecular model of cyclohexane. Locate one of the carbons, call it C1, and replace the equatorial hydrogen with a methyl group. Move to C2, and replace the equatorial hydrogen there with another methyl group. Note that both methyl groups are equatorial but on opposite sides of the ring, or in the trans conformation(ee).

Flip your model of trans-1,2-dimethylcyclohexane into the other chair conformation. Note that both substituents are now in the axial positions

The Stereoisomers have different stabilities. To understand the relationship between stereoisomerism and stability, look again at the cis and trans isomers of 1,2-dimethylcyclohexane in the chair conformations. The two conformations of cis-1,2-dimethylcyclohexane are equivalentno matter which conformation you look at, each has one axial and one equatorial methyl group: 1,3-dimethylcyclohexane This also has two stereo-isomers i.e cis and trans that are shown as follows:

For ease of comparison, rotate both stereoisomers so that C1 is in the back position of the chair conformation. Remember that for a cis stereoisomer of a dimethylcyclohexane both substituents either point up or point down, and for a trans stereoisomer, when one points up, the other points down. Now flip the two stereoisomers between their two chair conformations. The cis stereoisomer of 1,3-dimethylcyclohexane has one chair conformation in which both methyl groups are equatorial and another in which both methyl groups are axial. The trans stereoisomer has two equivalent chair forms, with one axial and one equatorial methyl group in each. Following the rule that equatorial groups are more stable than axial groups, the cis stereoisomer is more stable than the trans stereoisomer. 1,4-dimethylcyclohexane In cis-1,4-dimethylcyclohexane one methyl group is axial and the other is equatorial in either of the two conformations. Thus, they have the same energy level.

for the chair conformations of trans-1,4-dimethylcyclohexane both methyl groups are equatorial, and in the other both methyl groups are axial. The conformation in which the two methyl groups are equatorial is much more stable than the one in which they are both axial.

The trans isomer is more stable because in one conformation, both methyl groups are equatorial. Both cis conformations have an axial methyl group and thus are less stable. The difference in energy is about 1.7 kcal/mole.

Decalin A fused ring system is one in which adjacent rings have two atoms in common. By for the most important fused ring system is the decalin which exists in two diastereoisomeric forms, the cis and the trans. If cyclohexane ring system were to be planar as suggested by Baeyer, only one form of decalin with ring system junction hydrogens projecting on the same side of the molecule should exist. On the other hand, Sachse Mohr concept of puckered rings permits the existence of two isomeric forms of decalin. In fact, Mohr predicted that two isomeric forms of decalin molecule should exist before W.Huckel succeeded in preparing them. Both isomeric forms of decalin occur in petroleum ether.

The cyclohexane rings in both cis and trans-decalins exist in chair conformation. Cis-decalin is formed when both cyclohexane rings are joined through axial-equatorial bonds,

whereas, the trans-decalin is produced by joining the two cyclohexane rings through equatorial bonds only.

Trans-decalin has rigid geometry and cannot undergo ring inversion which would lead to a highly strained ring system with diaxial fusion. In contrast, cis decalin in which two cyclohexane rings are fused through axialequatorial bonds can readily undergo ring inversion by exchanging a,e bonds at ring junction. The two interconvertible chair conformations similar to cis-1,2-dimethylcyclohexane are equienergetic and so equally populated at room temperature. The ring inversion converts one conformer into its mirror image; cis-decalin is therefore, a non-resolvable racemate( )

The difference in enthalpy between cis- and trans-decalins can be determined by counting the number of gauche-butane interactions. In trans-decalin, since each ring is fused through the equatorial bonds, no gauche- butane interactions exist. In cis-decalin, there are three such interactions and the difference in enthalpy is therefore amounts to 10.5 KJ/mol (33.3 KJ/mol).Therefore, trans-decalin is more stable than cis.

UNIT II REACTION INTERMEDIATES AND HETERO CYCLIC COMPOUNDS

Free radicals A covalent bond may get cleaved homolytically to form fragments carrying odd electrons which are called free radicals. Free radical intermediates are generally involved in reactions which are carried out either at high temperature or under the influence of light. Some reactions may proceed even at room temperature via free radical mechanism, particularly in the presence of non-polar solvents and in the presence of compounds like peroxides which produce free radicals. Free radicals may be electrically charged ions or non-charged species. STRUCTURE AND GEOMETRY Simple alkyl radicals have a planar structure (i.e.) these have SP2 bonding with the odd electron in a p-orbital. The pyramidal structure is another possibility when the bonding may be SP3 and the odd electron is in an SP3 orbital. The planar structure is in keeping with loss of activity when a free radical is generated at a stereo centre. On adding HBr to 2-methyl-1-butane in the presence of peroxide, the product has a single stereo centre. However, equal amount of the R and S enantiomers are obtained. The product is a racemic mixture.

The carbon atom in the radical intermediate that bears the unpaired electron is planar and SP2 hybridized. This means that the three substituents bonded to it are all in the same plane. R and S enantiomers are obtained in equal amounts because HBr has equal access to both sides of the achiral radical.

STABILITY As in the case of carbocations, the stability of free radicals is tertiary > secondary > primary and primary and is explained on the basis of hyperconjugation. The stabilizing effects in allylic radicals and benzyl radical are due to resonance structures. The triphenyl methyl type radicals are no doubt stabilized by resonance the major cause of their stability is the steric hindrance to dimerization

Carbenes Carbenes are neutral intermediates having bivalent carbon, in which a carbon atom is covalently bonded to two other groups and has two valence electrons distributed between two non bonding orbital. When the two electrons are spin paired the carbons is a singlet, if the spins of the electrons are parallel it is a triplet.

STRUCTURE A singlet carbene is thought to possess a bent SP2 hybrid structure in which the paired electrons occupy the vacant SP2 orbital. A triplet carbene can be either bent SP2 hybrid with an electron in each unoccupied orbital or a linear SP hybrid with an electron in each of the unoccupied P-orbital. The singlet and triplet state of a carbene display different chemical behavior. Thus addition of singlet carbene to olefinic double bonds to form cyclopropane derivatives is much more stereo selective than addition of triplet carbenes. GENERATION Carbenes are obtained by thermal or photochemical decomposition of diazoalkanes. These can also be obtained by -elimination of a hydrogen halide from a halo form with base, or of a halogen from a gem dihalide with a metal.

REACTIONS These add to carbon double bonds and also to aromatic system and later case the initial product rearranges to give ring enlargement products.

When a carbene is generated in a three membered ring allenes are formed by rearrangement.

NITRENES STRUCTURE The nitrenes represent the nitrogen analogs of carbenes and may be generated in the singlet

GENERATION A nitrene can be generated via elimination or by the thermal decomposition of oxides

In the chemical behavior, the nitrenes are similar to carbenes; nitrenes get inserted into

some bonds e.g., C-H bond to give an amide. Aziridines are formed when nitrenes add to C=C bonds.

Rearrangements: Alkyl nitrenes do not generally give either of two proceeding reaction because the rearrangement is more rapid.

UNIT III STREOCHEMISTRY Stereochemistry is the branch of chemistry that deals with the study of the special structure of molecules and of influence of their structure on physical and chemical properties of compounds. In other words, stereochemistry deals with the study of physical and chemical properties of stereoisomers.

Isomers are different compounds with different properties that have the same molecular formula. This phenomenon is known as isomerism. Isomers that differ in the order in which their atoms are bonded are known as structural isomers or constitutional isomers. The order of atomic connections that defines a molecule is termed its constitution and two compounds are said to be constitutionally isomeric if they have same molecular formula but differ in the order in which their atoms are connected. Stereoisomerism is exhibited by isomers having the same structure but different configurations. That is, stereoisomers have the same constitution but differ only in the spatial orientation of their atoms. Optical isomerism is characterized by the compounds having the same structure but different configurations and because of their molecular asymmetry (Chirality) they are optically active. Geometrical isomerism or cis-trans-isomerism is characterized by compounds having the same structure but different configurations and because of their non-chiral (non-dissymmetric) nature they are not optically active, unless they happen to carry groups that contain asymmetric carbon atoms. This type of isomerism is exhibited by compounds that contain double bonds and certain ring compounds in which at least two ring atoms

contain unequal substituents. Geometrical isomerism is a special case of diastereoisomerism OPTICAL ACTIVITY Stereochemistry starts with the phenomenon of optical activity. The ability of a substance to rotate the plane of polarized light is known as optical activity. If a substance rotates the plane of polarized light, it is called optically active. On the other hand if a substance does not rotate the plane of polarized light, it is said to be optically inactive. Optical activity is detected and measured by an instrument called polarimeter. If a substance rotates the plane of polarized light in clockwise direction (right), it is called dextrorotatory and is designated as (+)-isomer. If the substance rotates the plane of polarized light in anticlockwise direction (left), it is known as laevorotatory and is designated as (-)-isomer. OPTICAL ACTIVITY AND CHIRALITY It is found that if a pure compound is optically active, the molecule is nonsuperimposable on its mirror image. The property of nonsuperimposability of a molecule on its mirror image is known as Chirality. If a molecule is not superimposable on its mirror image, it is chiral. If it is superimposable on its mirror image then it is achiral. Thus Chirality is a necessary and sufficient condition for optical activity. Thus if a molecule is chiral, it is non-superimposable on its mirror image and exhibits optical activity. On the other hand, if the molecule is achiral, it is superimposable on its mirror image and is optically inactive. ASYMMETRIC CARBON (Chiral carbon atom or Stereogenic centre) When a molecule contains just one asymmetric carbon atom, it is always chiral and hence optically active. Asymmetric carbon atom also called chiral carbon (or stereogenic carbon atom) is defined as a carbon atom attached to four different groups, no matter how slight the differences among the four groups. For example, optical activity is present in the following compound and optical activity has been detected even in such cases as 1-butanol-1-d, where one group is hydrogen and another is deuterium.

Although, molecules with one asymmetric carbon atom are always optically active, the presence of an asymmetric carbon is neither a necessary nor a sufficient condition for optical activity, since optical activity is present in molecules with no asymmetric carbon atoms (eg: biphenyls, allenes, ansa

compounds etc.) and some molecules with two or more asymmetric carbon atoms are superimposable on their mirror images and hence optically inactive (eg. meso-tartaric acid). PROJECTION FORMULAE black-board for drawing chemical structures is two dimensional. Hence, it is difficult to represent the three dimensional molecules on a two dimensional paper in their three dimensional reality. For this reason, a number of two dimensional projections have been introduced. WEDGE PROJECTION This projection is convenient to represent molecules with one and two asymmetric carbon atoms. This projection is constructed as follows: of the four groups attached to the tetrahedral carbon atom, two groups and the central carbon atom are placed in the plane of the paper such that, of the two remaining groups one lies above the plane and the other below the plane of the paper. The group which is above the plane of the paper is drawn with a bold or thick wedge and the one below the plane of the paper is drawn with a dotted wedge. The enantiomers of glyceraldehydes are represented below by the wedge projection. It is often convenient to place the longest carbon chain in the plane of the paper

FISCHER PROJECTION The wedge projection is convenient to represent three dimensional molecules with one and two asymmetric carbon atoms, wedge projections become increasingly complicated with increasing number of carbon atoms. For this reason, Emil Fischer introduced a projection in 1891 which is still in use. This projection is constructed as follows. The wedge projection or the three dimensional model of the molecule, is so rotated that two groups attached to the asymmetric carbon atom are above the plane of the paper and the two groups are below the plane of the paper. The molecule is then represented by two lines intersecting at right angles to each other. The asymmetric

carbon atom is at the point of intersection which is usually not shown. Then, the groups which are above the plane of the paper are attached to the horizontal line and those groups which are below the plane are attached to the vertical line. It is convenient to place the longest carbon chain vertically. The construction of Fischer projection is illustrated with glyceraldehydes as an example.

R AND S NOMENCLATURE A self-consistent and unambiguous system of configurational nomenclature based on the three-dimensional structures of molecules was first introduced by Cahn and Ingold (1951) and subsequently elaborated by Cahn, Ingold, and Prelog (1955,1966).The system is known as CIP nomenclature after the names of the authors. According to this system, the configuration of a molecule is specified uniquely either as R (from rectus, Latin for right) or as S (from sinister,Latin for left) which is independent of nomenclature and numbering.

The following sequence rules summarize the Cahn-Ingold-Prelog notational system. 1. Identify the four different atoms or groups attached to the stereogenic center. 2. Rank the atoms or groups based on the priority rules (see the list following this one). 3. Orient a projection of the molecule in space so that the group or atom of lowest rank is eclipsed by the stereogenic center. 4. Determine the ranking of the remaining visible atoms or groups. 5. If the ranking declines in a clockwise direction, the configuration is R; if the ranking declines in a counterclockwise direction, the configuration is S. The priority rules rank atoms and groups based on atomic mass. The following list summarizes these rules. 1. For the four atoms directly attached to the stereogenic center, the higher the atomic mass, the higher the rank. 2. If two or more atoms directly attached to the stereogenic center have the same mass, work outward along the chains of the groups they are in, atom by atom, until a point of difference is reached. The rank is assigned at this point of difference, based on the difference in atomic mass. 3. If a group contains multiple bonds, the doubly or triply bonded atoms are counted as two or three of those atoms, respectively. Thus the carbonyl group is considered to have two carbon-oxygen bonds, one actual and one theoretical.

A cyano group is considered to have three carbon-nitrogen bonds, one actual and two theoretical. For comparison purposes, an actual bond ranks higher than a theoretical bond of the same type. For example, when ranking the cyano group against

the displayed group takes priority, due to its three actual carbon-nitrogen bonds. The sequence rules can be illustrated by applying them to lactic acid.

1. The four atoms or groups around the stereogenic carbon are CH3, H, COOH, and OH. 2. The ranking based on atomic weights is oxygen > carbon > hydrogen. The ranking of the carbon-containing groups is COOH > CH3. 3. The overall priority is thus OH > COOH > CH3 > H. Viewing the molecule in such a way that the lowest ranked atom is eclipsed by the stereogenic center reveals that the remaining groups decline in rank in a clockwise direction. Thus, the stereogenic carbon has an R configuration. Gaining the proper perspective for eclipsing the lowest ranked atom or group by the stereogenic carbon can be difficult. Try using an eclipsed downward sawhorse projection of the molecule. This projection allows rotation of the sawhorse axis so the atom or group of lowest rank can be placed at the bottom, thus allowing the point of view to be always from the top, or front, of the projection. Such a sawhorse projection must be drawn directly from a Fischer projection without any rotation. An eclipsed downward sawhorse projection of ( R)-lactic acid can be drawn this way.

The projection can be abbreviated in this manner.

Rotation on the carbon-carbon bond to put the hydrogen atom at the bottom of the projection looks like this.

Viewing from the top eclipses the hydrogen atom.

The clockwise direction of the ranking is then easily seen. RS notation can also be generated from Fischer projections; however, because Fischer projections are strictly two-dimensional representations of three-dimensional molecules, only certain manipulations are allowed. One such manipulation is the interchange of any two pairs of substituents. An interchange converts an enantiomer to its mirror image. Interchanging two pairs of substituents produces the original projection. Here is an example using a Fischer projection of (R)-lactic acid.

Verify its R or S configuration by using the following general steps (diagrams follow). 1. Interchange the atom or group of lowest rank with the atom or group at the bottom of the Fischer projection. 2. Interchange the atoms or groups on the remaining positions until rank order is established. 3. Determine whether the ranking defines a clockwise or counterclockwise direction. If clockwise, the projection is an R configuration; if counterclockwise, it is an S configuration. 4. The configuration of the original structure is determined by counting the number of interchanges made in step 2. If an odd number were made, the original configuration is opposite that of the projection. If an even number of interchanges were made, the original configuration and the projection are the same.

GEOMETRICAL ISOMERISM The geometrical isomerism arises when atoms or groups are arranged differently in space due to restricted rotation of a bond or bonds in a molecule.

E.g. 1) Two different spatial arrangements of methyl groups about a double bond in 2-butene give rise to the following geometrical isomers. i.e., cis-2-butene and trans-2-butene

Above two forms are not inter convertible due to restricted rotation of double bond. In the cis isomer, the two methyl groups are arranged on the same side of a double bond. Whereas in the trans isomer, they are on the opposite side. 2) There are two geometrical isomers (cis & trans) possible in case of 1,4 dimethylcyclohexane as shown below:

In the above geometrical isomers, the methyl groups are arranged differently about the plane of the cyclohexane ring. These isomers are not inter convertible since it is not possible to rotate the bonds in the cyclohexane ring. * The geometrical isomers often show different physical and chemical properties. The difference in their physical properties is more significant when there is more difference in their polarity. * Usually the dipole moment of cis-isomers is greater than that of trans isomers. Hence the cis isomers usually have more solubility in polar solvents.

* In general, the trans isomers are more stable than cis isomers.

E-Z NOTATION The simple convention of denoting the geometrical isomers by cis/trans descriptors is not sufficient when there are more than two different substituents on a double bond. To differentiate the stereochemistry in them, a new system of nomenclature known as the E-Z notation method is to be adopted. According to this method, if the groups with higher priorities are present on the opposite sides of the double bond, that isomer is denoted by E. Where E = Entgegen ( the German word for 'opposite') However, if the groups with higher priorities are on the same side of the double bond, that isomer is denoted by Z. Where Z = Zusammen (the German word for 'together') The letters E and Z are represented within parentheses and are separated from the rest of the name with a hyphen.

Step by step procedure to determine the E-Z configuration: The following procedure is to be adopted to denote the geometrical isomers by E & Z descriptors. First determine the higher priority group on each end of the double bond. If the higher priority groups are on the opposite sides of double bond, the isomer is denoted by the descriptor, E. Otherwise if they are on the same side of double bond, the Z descriptor must be used.

The priorities are assigned by following Cahn-Ingold-Prelog sequence rules (CAN rules) described below. Rank the atoms directly attached to the olefinic carbon according to their atomic number. High priority is given to the atom with higher atomic number. 1. If isotopes of same element are present, the higher priority is given to the isotope with higher atomic mass. E.g. The Deuterium isotope (H2 or D) has more priority than protium (H1 or H).The C13 isotope has more priority than C12. 2. If the atoms are still identical, examine the next atoms along the chain until a first point of difference is found. This is done by making a list of atoms linked directly to the first atom. Each list is arranged in order of decreasing atomic number. Then the higher priority is given to the list which contain atom with higher atomic number at first point of difference. E.g. Examine the lists of atoms directly linked to the highlighted carbons in the following compound, (2Z)-2-tert-Butyl-3-methylpent-2-en-1-ol.

The (C,H,H) list has more priority over (H,H,H). Whereas, the (O,H,H) has more priority over (C,C,C). Since the groups with highest priorities are on the same side of the double bond, the descriptor, Z is used to represent the stereochemistry of groups at double bond. 3. The multiple bonds are counted as multiples of that same atom i.e., each bond is treated as if it were another bond to that type of atom. E.g.

Illustrations: 1) The cis and trans 2-butenes can also be represented as Z and E isomers respectively.

Since the double bond is at 2nd carbon of the butene, the number 2 is used before the descriptors i.e., '2Z' or '2E' . 2) There are four geometrical isomers possible with 3-methylhexa-2,4diene as shown below. The geometries at each double bond are clearly mentioned by the numbers: 2 and 4.

3) If the double bond has two similar groups on the same carbon, then there is no need of descriptor. For example, in the following compound, 2,3,4-trimethylhexa-2,4-diene, the double bond on 1st carbon has two methyl groups. Hence there is no need of the descriptor for this double bond.

GEOMETRICAL ISOMERISM IN OXIMES The oximes are formed when carbonyl compounds are treated with hydroxyl amine. These are represented as:

Where R & R1 are hydrogens; or alkyl or aryl groups. The oximes are of two types: 1) Aldoximes: These are derived from aldehydes. In this case, at least either R or R1 is hydrogen. 2) Ketoximes: These are derived from ketones. In this case, both R or R1are alkyl or aryl groups only.

The oximes show geometrical isomerism due to restricted rotation of C=N bond. Two geometrical forms are possible for the oximes as shown below.

The descriptors, syn and anti are used to distinguish them.

* In case of aldoximes, the syn form is the one in which both the hydrogen and the hydroxyl (-OH) group are on the same side of the C=N. Whereas in the anti form, they are on the opposite side. E.g. The syn and anti forms of acetaldoxime are shown below.

* However with ketoximes, the syn and anti descriptors indicate the spatial relationship between the first group cited in the name and the hydroxyl group. For example, the following ketoxime of butanone can be named as either syn methyl ethyl ketoxime or anti ethyl methyl ketoxime.

E-Z notation of oximes: The geometrical isomers are better differentiated by using E-Z notations. The Z oxime has hydroxyl group and the group with higher priority on the same side of C=N. However in the E oxime, they are arranged on the opposite sides of the C=N. E.g. The syn acetaldoxime is named as (E)-acetaldoxime, since the hydroxy group and the group with higher priority i.e., methyl group are on the different sides of the C=N. Whereas the anti form is named as (Z)acetaldoxime.

IUPAC SYSTEM OF NOMENCLATURE OF OXIMES: * In the IUPAC system of nomenclature, the oximes are named as: Nhydroxyalkanimines, where the C=N group is represented by the suffix, imine and the -OH group on nitrogen is represented by the prefix, Nhydroxy. E.g. The syn and anti forms of acetaldoxime are named as follows: