Msc-Chemistry.Pdf

BHARATHIDASAN UNIVERSITY (Re-accredited with ‘A’ Grade by NAAC) CENTRE FOR DISTANCE EDUCATION PALKALAIPERUR, TIRUCHIRAPPALLI – 24

M.Sc., CHEMISTRY Major Paper -I Organic Chemistry - I

I - Year

Copy right reserved For Private Circulation only

Lesson Writter

Dr. T. Vimala, Associate Professor PG & Research Department of Chemistry Seethalakshmi Ramaswami College, Tiruchirappalli-620 002.

MAJOR PAPER I – ORGANIC CHEMISTRY UNIT – I Nomenclature, Reactive Intermediates, Methods of Determining Reaction Methods 1.1. Nomenclature of alicyclic, bicyclic and tricyclic compounds. Nomenclature of heterocycles having not more than two hetero atoms such as oxygen, nitrogen and sulphur. 1.2. Aromatic character: six-, five-, seven-, and eight-membered rings – Other systems with aromatic sextets Huckel’s theory of aromaticity, Concept of homoaromaticity and antiaromaticity, systems with 2,4,8 and 10 electrons, systems of more than 10 electrons, alternant and non-alternant hydrocarbons (azulene type). Bonding properties of systems with (4n + 2) electrons and 4n electrons, Heteraromatic molecules. Annulenes and sydnones and fullerenes. 1.3. Thermodynamic and kinetic aspects, Hammond’s postulate, isotope effects. Energy profile diagrams – Intermediate versus transition state, Product analysis and its importance, Crossover experiments, Kinetic methods, Stereochemical studies, Isotopic and substitutent effects. UNIT – II Stereochemistry 2.1 Fundamentals of Organic Stereochemistry: Principles of symmetry – Stereoisomerism – Optical isomerism – Definitions – Conventions used in stereochemistry: Newman, Sawhorse and Fischer notations and interconversions and representations. Nomenclature, correlation of configuration. Cahn – Ingold – Prelog rules for simple molecules. Optical activity and chirality – Types of molecules exhibiting optical activity – Fischer projection – Absolute configuration. Molecules with more than one chiral centre – Molecular chirality – Atropisomerism – Biphenyls,

allenes and spiranes. Methods of determining configuration. Enantiomerism of compounds containing chiral heteroatoms. 2.2 Geometrical Isomerism E & Z Nomenclature, Determination of configuration of geometrical isomers, Stereospecific and stereoselective synthesis – [Elementary examples]. 2.3 Basic concepts of conformational analysis – cyclohexane and decalins. UNIT-III Substitution Reactions 3.1 Aliphatic Nucleophilic substitution – Mechanisms – Effect of structure – Stereochemical factors – Neighbouring group participation, substitutions at allylic and vinylic carbons. Correlation of structure with reactivity – Solvent effects. 3.2 Aliphatic Electrophilic Substitution SE2, SEi and SE1 mechanisms, Diazonium coupling reactions. 3.3 Aromatic Nucleophilic substituion – SN1 SNAr, Benzyne mechanism – reactivity orientation. 3.4 Aromatic electrophilic substitution reaction – Orientaion, reactivity and mechanisms based on transition state theory with suitable reactions, - Origins of Hammett equation – Principles of Hammett correlation – Effect of structure ofn reaction mechanisms Hammett parameters;  and , modified forms of Hammett equation. Taft Equation.

UNIT-IV Addition and Elimination Reactions 4.1 Addition to carbon – carbon multiple bonds: Electrophilic, nucleophilic and free radical additions – Orientation of the addition – Stereochemical factors influencing the addition of bromine and hydrogen bromide, hydroxylation, hydroboration leading to formation of alcohols. Addition to carbonyl and conjugated carbonyl systems – Mechanism – Grignard

reagents – 1,2 and 1,4-additions (dimethyllithiumcuparate), Benzoin, Knovenagel, Stobbe and Darzen’sglycidic ester condensation and Reformatsky reactions. 4.2 Elimination Reactions: Mechanisms; E1, E2, E1cB – Stereochemistry of elimination, Hofmann and Saytzeff rules – Competition between elimination and substituion – Pyrolyticcis elimination, Chugaev reaction – Examples sucha as dehydration, dehydrohalogenatio, Hofmann degradation, Cope elimination – Bredt’s rule with examples.

UNIT-V Organic Photochemistry & Pericyclic Reactions 5.1 Organic Photochemistry – Fundamental concepts – Jablonski diagram – Energy transfer, characteristics of photoreactions, photoreduction and photoxidation, photoreactions of ketones and enones, Norrish Type I and II reactions. Photochemistry of alkenes, dienes and aromatic compounds, Photoadditions – Barton reaction – ParternoBuchi reaction. 5.2 Concerted reactions – stereochemistry-orbital symmetry and concerted symmetry and correlation diagram – Frontier molecular orbital approach – Woodward and Hoffmann rules – Electrocylcic reactions – cycloaddition reactions – sigmatropic rearrangements – selection rules and examples with simple molecules – 1,3 and 1,5 hydrogent shifts – cope and Claisen rearrangements. Other molecular rearrangements

References 1. J. March, Advanced Organic Chemistry: Reactions. Mechanisms and Structure, 5th ed., Wiley, 2000. 2. D. Nasipuri, Stereochemistry of organic compounds-Principles and applications,New Age International, 2nd Edition, 2002. 3 I.L. Finar, Organic Chemistry, Vol. II, 5th ed., ELBS 1975.

4. J.M. Coxon, B. Halton, Organic Photochemistry, Camb. Uni. Press, 2nd edition, 1987. 5. G.R. Chatwal, Organic Phtochemistry, Himalaya Publicaions house, 1st edition, 1998. 6. P.S. Kalsi, Stereochemistry, Wiley eastern limited, New Delhi, 1990. 7. S.H. Pine, J.B. Hendrickson, D.. Cram and G.S. Hammond, Organic chemistry, McGraw Hill, 4th ed., 1980. 8. T.H. Lowry and K.S. Richardson, Mechanism and Theroy in Organic Chemistry, Harper and Row, 1976. 9. F.A. Carey and R.J. Sundberg, Advanced Organic Chemistry, Parts A & B, Plenum, 2002.

CONTENT

UNIT TITLE PAGE NO

I. Nomenclature, Reactive intermediates, Methods of 1 Determining reaction Methods

II. Stereochemistry 49

III. Substitution Reactions 84

IV. Addition and Elimination Reactions 126

V. Organic Photochemistry & Pericyclic Reactions 167

Unit - I 1.1 Nomenclature Saturated and unsaturated monocyclic hydrocarbons are treated like their acyclic analogues but with the specifying prefix cyclo in front of the name. Monovalent substituent groups derived there from are again given the ending...yl, bivalent groups the ending...diyl (formerly...diyl) when different C atoms are involved and... ylidene or... 1,1-diyl when the free valences are at the same carbon atom. In numbering them, positions with free valences have precedence; only then are double and triple bonds together and thereafter double bonds given the lowest locants possible.

The designations benzene, phenyl and ,m,p-phenylene are retained as trivial names.

Monocyclic polyenes containing the maximum number of non-cumulative double bonds (for short called: mancude systems) and having the general composition CnHn or CnHn+1 (n > 6) can also be named as [n] annulenes.

Fused Polycyclic Hydrocarbons The nomenclature of these compounds in which at least two highly unsaturated rings are fused together through at least two common C-atoms is based on an extended series of trivial names. Systems comprising only benzene units and their substitution products are generally designated as arenes or, traditionally, aromatics. Fused hydrocarbon systems for which no trivial names are retained are systematically named as follows. That component that has the largest ring or/and that – if it is a trivial system according to Table-contains the largest number of rings is defined as parent (or base or primary or main) component. All other components are attached in the form of prefixes to the parent name by changing their ending... ene to ... eno. The following abbreviated prefix forms are retained. Acenaphtho from Naphtho From Acenaphthylene Naphthalene Antha from Anthracene Perylo from Perylene Benzo from Benzene Phenanthro from Phenanthrene With the exception of benzo, fusion prefixes for monocyclic systems are treated as exemplified for cyclopenta, cyclohepta etc. It should be noted here that for fused polycyclic systems the ending... ene always indicates the maximum number of non-cumulative double bonds, that is, a mancude system.

For the following compounds Chem. Abstr. Incomprehensibly uses the von Baeyer names bicyclo [4.2.0] octa-1,3,5,7-tetraene and 1H-bicyclo[4.1.0] hepta- 1.36-triene that totally disregard the aromatic character of these compounds.

Bridged Polycyclic Hydrocarbons Von Baeyar System Saturated cyclic hydrocarbons containing two or more rings in which at least two rings have at least two common C-atoms are specified as bi-, tri-, tetra-, etc. –cycoalkanes. The total number of rings present evidently equals the number of C-C cleavages necessary to obtain an open chain compound. The names of such compounds are constructed stepwise in the following manner. a) the actual tridimensional structure is transformed into an appropriate planar representation, b) That ring is selected as main ring which includes as many skeletal atoms as possible, c) The largest possible carbon chain that connects two C-atoms of the main ring (consisting itself of tow branches) is defined as the main bridge. The corresponding points of connection are called bridge-heads, d) To assemble the full name the numbers of C atoms of both branches of the main ring, the main bridge and the secondary bridges, if present, are cited in descending order, separated by full stops, and placed in square brackets after the term cyclo. e) The numbering begins at the first bridgehead, tracing first the largest branch of the main ring up to the second bridgehead and then the next largest branch back to the first bridgehead. Next comes the (longest possible) main bridge which should divide the main ring as symmetrically as possible and then the secondary bridges. The bridgeheads of the secondary bridges are specified by superscripts chosen as small as possible in the framework of the above rules.

For compounds containing intact benzenoid skeletons the nomenclature of fused polycycles or of parent structures substituted by side chains is much more reliable and recommendable.

Heterocyclic compounds containing two or more hetero – atoms Many heterocyclic systems have trivial names. The following is the systematic method of nomenclature.

(i) The names of monocyclic compounds are derived by a prefix (or prefixes) indicating the nature of the hetero-atoms present, and eliding the ‘a’ where necessary, e.g., oxygen, oxa; sulphur, thia; nitrogen, aza; silicon, sila; phosphorus, phospha. When two or more of the same hetero-atoms are present, the prefixes di, tri, etc. are used, e.g., dioxa, triaza. If the hetero-atoms are different, their order of citation starts with the hetero-atom of as high a group in the periodic table and as low an atomic number in that group. Thus, the order of naming will be O, S, N, P, Si, e.g., thiaza (S then N). (ii) The size of a monocyclic ring from 3 to 10 is indicated by a stem: 3, ir (tri); 4, et (tetra); 5, ol; 6, in; 7, ep (hepta); 8, oc (octa); 9, on (nona); 10, ec (deca). (iii) The state of hydrogenation is indicated in the suffix, or by the prefixes dihydro, tetrahydro, etc., or by prefixing the name of the parent unsaturated compound with the symbol H preceded by a number indicating the position of saturation. (iv) (a) In a monocyclic compound containing only one hetero-atom, numbering starts at this atom. (b) The ring is numbered to give substituents or other hetero-atoms the lowest numbers possible. If the hetero-atoms are different, then numbering starts at the atom cited first according to the rule in (i) and proceeds round the ring in order of precedence.

Fused heterocyclic systems. When one heterocyclic ring is present, this is chosen as the parent compound. If more than one heterocyclic ring is present, the order of preference is given to the nitrogen-containing component (nitrogen rings are the most common). For a component containing a herero-atom other than nitrogen, the order of preference is that in (i) above (O before S, etc.). For the purpose numbering, the structure is written with the greatest number of rings in a horizontal position and a maximum number of rings above and to the right of the horizontal row. Numbering is then carried out (usually) in a clockwise direction starting with the uppermost ring farthest to right and omitting atoms at ring junctions.

1.2 Aromaticity Concept of aromaticity Benzene and other organic compounds which resemble Benzene in certain characteristic properties are called aromatic compounds. These characteristic properties constitute what in commonly known as aromatic character or aromaticity. Such important properties are given below. (i) Unusual stalility Aromatic compounds are highly stable as shown by their low heats of combustion. For example, heat of hydrogenation of Benzene is only 49. kcal/mole as compared to that of the hypothetical cyclohexatriene (85.8 kcal/mole). Similarly, heat of combustion of benzene (789.1 kcal) is low as compared with that for cyclohexatriene (824.1 kcal). (ii) Substitution rather than addition Aromatic compounds although possess double bonds do not undergo addition reactions readily. On the other hand, they undergo electrophilic substitutions like nitration halogenation, sulphonation and Friedel-Crafts reactions.

(iii) Resistant to oxidation Aromatic compounds are resistant to oxidation. They are not oxidised by cold alk. KMnO4, HNO3 etc. (iv) Properties different from aliphatic compounds The properties of substituted benzenes are often different from those of analogous aliphatic compounds. Aniline is less basic than aliphatic amines, and it reacts with HNO2 in the presence of HCl to form benzene diazonium chloride. Phenol is a stronger acid than the alcohols. Halobenzenes are much less reactive than aliphatic halogen compounds. Molecular Orbital Theory and Huckel’s Rule Huckel’s rule: Cyclic, planar systems containing (4n+2)  electrons are aromatic where ‘n’ is any positive integer including zero. The rule predicts that rings of 2,6,10,14 etc. electrons will be aromatic while rings of 4,8,12 etc will not be. Huckel’s rule in based on molecular orbital calculations Molecular Orbital Diagram for Benzene In benzene, the carbon atoms are in the trigonal (SP2) state of hybridization formed by the hybridization of 2s, 2Px and 2Py orbitals. These hybrid orbitals, by overlapping with the hybrid orbitals of the neighbouring carbon atoms form the C-C  bonds. The remaining hybrid orbitals overlap with the 1s orbitals of the six hydrogen atoms to form the C-H bonds.

Each carbon atom has a 2pz orbital oriented perpendicular to the plane of the ring. These 2Pz orbitals interact laterally and forms six distinct molecular orbitals. The energies of these orbitals can be calculated using the expression  The energy levels of benzene are shown below.

 - 2  -  E  -  +   + 2 magnittude of  is negative. is the energy of the atomic orbital There are three bonding and three antibonding molecular orbitals. The six  electons occupey the three bonding molecular orbitals. Therefore, due to overlapping the energy of the system is reduced and so it is stable or aromatic. Craig’s Rule Craig has proposed an empirical rule which is applicable to compounds possessing C2 axis of symmetry. The structural formula is first labeled with symbols  and  as for as possible alternately. The molecule is rotated through C2 axis. For example

f = No. of  centers outside the C2 axis (Total number of  and  outside the C2 axis divided by 2) 44+ In the above compound f4== 2 g = Number of interconversions of  and  by rotation about the C2 axis. g in this compound is 0. f + g = 4 + 0 = 4. If f + g is even the molecule may be aromatic and if it is odd it may be nonaromatic.

f + g = 3 + 0 = 3 so nonaromatic According to craigs rule, pentalene is nonaromatic and it is so.

f + g = 5 + 0 = 5 so heptalene is noasomatic = 5 so heptalene is nonaromatic f + g = 4 so aromatic Example 5

66+ f= = 6 g = 2 2 f + g = 6 + 2 = 8 So aromatic Effect of Aromaticity on Bond Lengths The length of a carbon-carbon single bond is 1.54A and that of double bond is 1.34 A. In benzene bond alternation is not observed. All the bonds are equivalent with bond length 1.39 A. In all aromatic compounds bond length alernation is not observed even though there are some variation in bond length. For example

1,2 bonds are shorter than 2,3 bonds. This is due to partial bond fixation and is found in all fused aromatic system. Cyclopropenium cation (+) which contains 2 electrons is aromatic according to Huckel’s rule. X-ray diffraction study of triphenylcyclopropenium cation shows that all the carbon-carbon bonds in the three membered ring are equivalent. Cycloheptatrienium cation is aromatic. An important derivative of this compound is tropolene. X-ray crystallographic study of cupric tropolone shows the system is planar heptagon with C-C bond lengths of 1.40A.

In ferrocene all the C-C bonds are equivalent with bond length 1.40 A. In nonaromatic cyclooctatetraene bond length alternation is observed. The C-C single bonds are of length 1.50A and the double bond length 1.35 A.  Bond length alternation does not, in general, occur in aromatic compounds.

Resonance Energies According to valence bond theory the resonance energy is the difference between the calculated energy of the most stable canonical form and the true energy of the molecule. The resonance energy can be determined using heats of combustion. Substance Heat of combustion Resonance energy (k.cal.mol) Observed Calculated Eltylene 337.2 337.2 - 1,3-Butadiene 608.5 611.5 3.0 Benzene 789.1 825.1 36.0 Naphthalene 1249.7 1310.7 61.0 Anthracene 1712.1 1795.6 83.5

Electronic absorption spectrum The abesorption spectrum of benzene shows three band systems at 255, 205 and 183 nm in the ultraviolet absorption spectra of polyenes and benzene. Compound Grp I II III Colour Benzene 183 205 255 Colourless Naphthalene 221 285 311 Colourless Anthracene 251 374 - Colourless Naphthacene 274 471 - Orange Pentacene 303 582 - Violet

Induced Ring Current In aromatic molecules the -electrons are not confined to individual atoms or bonds. The diamagnetic currents are therefore not limited to atoms but involve an extended orbit around the ring. This induced ring current produces secondary magnetic field (induced magnetic field) which opposes the external magnetic field above and within the ring and reinforces outside the ring.

Protons outside the ring therefore resonate at lower field where as protons above or within the ring resonate at higher applied field strength The olefinic protons usually absorb in the range  4.9 to 5.7. The protons of nonaromatic cyclooctatetraene absorbs at  5.7. In benzene the protons are strongly deshielded due to induced magnetic field and absorb at  7.2. On the other hand, a proton present above or within the aromatic ring absorbs at higher field. In [10] paracyclophane the two central methylene groups are abnormally shielded and these protons absorb at higher field.

Some macrocyclic aromatic hydrocarbons possess protons not only outside the ring but also inside the ring. For Example

The external protons (12H) are deshielded and absorb at  8.9 where internal protons (6H) are highly shielded and absorb at  -1.8 In aromatic ions, the proton absorbs at -1.8 higher the electron density the greater the shielding. There fore the protons in cyclopentadienide anion absorbs at  5.3 and that of cycloheptatrienium cation absorbs at  9.1.

Aromaticity of Heterocycelic Compounds 5. Membered heterocyclic compounds In furan, pyrrole and thiophene, the four pz orbitals of the four carbon atom overlaps with the filled orbital containing the lone pair of the hetero atom.

This lateral overlap produces five molecular orbitals, three bonding and two antibonding. The three bonding orbitals contains the aromatic sextet. In pyrrole since the lone pair is involved in aromatic sextet, it is not available to form a bond with proton. So it is a weaker base. The aromatic character decreases in the order thiophene > pyrrole > furan due to increase in the electronegativity of the hetero atom. Six membered heterocyclic compounds Pyridine resembles benzene in its aromatic character. It is even more resistant to oxidation than benzene. The unshared pair (lone pair) of the nitrogen does not participate in the formation of aromatic sextet. Therefore, it is a strong base and the derivatives such as N-oxides or pyridinium ions are still aromatie. Six-membered heterocyclic compounds containing oxygen or sulphur is not aromatic because it is non-conjugated.

An aromatic sextet can only occur if the ring carries a positive charge.

Each carbon atom contributes one  electron and oxygen or sulphur contributes one  electron. Pyrones and thiapyrones are derived from the parent systems by replacement of the methylene group by a carbonyl group. The resonance structures for these compounds indicate a contribution from a pyrilium or thiapyrilium cation.

The carbonyl group of the pyrone does not give the usual carbonyl derivatives. Alternant and Non-Alternant Hydrocarbons Aromatic hydrocarbons can be divided into two types. Alternant and non alternant hydrocarbons. The carbon atoms are labeled alternately as  and . In alternant hydrocarbon the same letter will not be present in the adjacent carbon atoms. For example

In non-alternant aromatic hydrocarbon same letter will be present in adjacent carbon atoms.

In alternant hydrocarbons, the bonding orbital with an energy – E there is an antibonding orbital with energy + E. For example in benzene.

 - 2   -   +   + 2 Odd alternant hydrocarbons (which must be cation, anion or free radical) in addition to equal and opposite bonding and antibonding orbitals also have a nonbonding orbital of zero energy. For example in the benzyl system

The cation has an unoccupied nonbonding orbital, the free radical has one electron and the carbanion has two electrons in non-bonding orbital. For nonalternant hydrocarbons the energies of the bonding and antibonding orbitals are not equal and opposite. Non-Benzenoid Aromatic Compounds Systems with 2 Electrons The cyclopropenium cation according to Huckel’s rule (4n+2 = 2; n = 0) is the simplest possible aromatic system. It may be represented as a resonance hybrid of the following structures.

Hence the cyclopropenyl cation should be stable. In practical, several cyelopropenium salts have been prepared. The NMR spectrum of the cation shows that there in only one type of phenyl ring in the following compounds

The parent cyclopropenium cation itself has been prepared The NMR spectrum of cyclopro penium ion shows only one signal at  11.1. (very low field) confirming the aromatic character. Cyclopropenone Cyclopropenone and its derivatives can be considered as cyclopropenium ions. Diphenylcyclopropenone was found to have a dipole moment of 5.08 D which is much larger than those of other ketones. (Benzophenone 2.97 D; acetone 2.8D). It was found to be basic. The above observations can be accounted only by considering the structure as

Methylenecyclopropene (Triafulvene) Methylene cyclopropene and its derivatives are also of interest, as both classical and dipolar structures can be written. The dicyano derivative for example, has been found to have very high dipole moment (7.9 D) in agreement with this formulation. Cyclobutadienium Dication

The cyclobutadienium dication, a 2 electron system has not been prepared, but two substituted dications have been obtained. Systems of Four  Electrons - Antiaromaticity Cyclobutadiene, cyclopropenyl anion and cyclopentadienyl cation contain 4 electrons. They are not nonaromatic but antiaromatic. This antiaromatic character can be explained by molecular orbital theory. For example in butadiene the 4 Pz orbitals overlap laterally and produce 4 molecular orbitals. It will behave like a diradical. Here the system is destabilized due to conjugation and it is said to be antiaromatic. Planar cyclic conjucated 4n electron system is antiaromatic. Similarly in cyclopropenyl anion conjugation destabilisis the molecule. An evidence for

antiaromatic character is compound I (R=COPh) loses its proton by hydrogen exchange reaction about 6000 times more slowly than compound II when R = CN, the ratio is about 10,000. This indicates that compound I is much more reluctant to form carbanion (cyclopropenyl anion) than compound II, which forms ordinary carbanion. Cyclopentadienyl cation has also 4 electrons. The ion has been prepared and has been shown to be a diradical. Compound III on treatment AgClO4 undergoes solvolysis readily while compound IV does not which shows antiaromatic character of the intermediate cation.

Stable Cyclobutadienes Cyclobutadienes that are stable at room temperature fall into three classes. 1.cyclobutadienes which contain bulky substituents.

These compounds are relatively stable because dimerization is sterically hindered. The peak at  5.38 in the NMR spectrum of tri.t.bultylcyclobutadiene indicates that the compound is non aromatic. X-ray crystallographic study of thia compound showed that the central ring is a rectancular diene with single and double bond lengths of 1.600 and 1.344 Å respectively. photoelectron spectroscopy showed that it is not a diradical. 2. Cyclobutadiene with two electron donating and two electron-withdrawing groups and these compounds are stable in the presence of water. The stability is due to resonance called the push-pull effect or captodative effect.

3. Derivatives in which the cyclobutadiene system is fused to aromatic rings Annellation can result in an ‘empty’ central ring biphenylene (Annellation-In fused systems some rings give up part of their aromaticity ( e’s) to adjacent rings). The system is stable because the electron density is withdrawn from the ring by the metal and the system contains only aromatic duet(2e).

Systems with 6 Electrons Cyclobutadienide Dianion

The tetraethyl derivative has been investigated and it has been concluded that it has no special stability. On the other hand dibenzocyclobutadiene dianion is readily prepared by reaction of biphenylene with Na or K in THF and this has some stability. Cycloepntadienide Anion Cyclopentadiene is nonaromatic, undergoes self condensation (Diels-Alder reaction) rapidly to form dicyclopentadiene. The acidic nature of cyclopentadiene was recognized by thiele (1900), who prepared cyclopentadienide anion by the action of K in an insert solvent.

A satisfactory method is to use phLi indtead of K (Doering & Depuy, 1953). The aromaticity of the cyclorpentadienide anion is confirmed by the NMR spectrum which shows a peak at  5.34. This estabilishes the presence of a ring current in the negatively charged ring. The cyclopentadienide anion reacts readily with electrophiles.

During electrophilic substitution, dimeric dicyclopentadienes are formed. Reaction with p-toluenesulphonyl hydrazide gives the ylide diazocyclopentadiene. A variety of related ylides have been prepared. All these ylides have very large dipole moments (~7.OD) and are aromatic.

These compounds undergo electophilic substitution reaction in the cyclopentadienyl ring.

Ferrocene is aromatic. The IR spectrum shows only one type of C-H stretching mode. Ferrocene undergoes electrophilic substitution reactions. During nitration or bromination the iron atom is oxidised from ferrous to the ferric state.

Tropylium Cation The cycloheptariene molucule has one saturated carbon atom and cannot therefore be fully conjugated. It behaves as an olefin. On the other hand, the cycloheptatrienium cation (tropylium cation) has six -electrons and according to Huckel’s rule should posses aromaticity. Preparation

The aromatic character is confirmed by spectral studies. The NMR spectrum shows a singlet at  9.28, the position of the chemical shift being in good agreement with that calculated on the basis of the benzere ring current and 1/7 of a positive charge on each carbon atom. The uv absorption spectrum shows maxima at 247 and 275 nm. The tropylium cation reacts with a variety of nuclophiles.

Tropone Cycloheptatrienone (tropone) is a resonance hybrid of the classical structure and tropylium cation structure.

It does not react with 2,4-dinitrophenylhydrazine and reacts with hydroxylamine only one heating. The contribution of the ionic structure is confirmed by the dipole moment (4.17D) which is relatively high compared with that of benzophenone (2.97D) and acetone (2.8D). It is also confirmed by the fact that tropone readily adds a proton to give the hydroxytropylium cation.

The resonance energy of tropone, from heats of combustion is ~29 kcals/mole. The uv spectrum of tropone shows maxima at 225, 297 and 310 nm. The IR spectrum shows C-H stretching bands at 3060-3010 cm-1, similar to benzene, and C=O stretching band at 1638 cm-1, a lower wave number than for normal ketones.

Tropolone The tropolone ring system (2-hydroxytropone) occurs in several natural products. It possesses marked aromatic character. The proximity of the –OH group to the carbonyl group facilitiates intramolecular hydrogen bonding. This is conformed by a shift in the -OH absorption in the IR from the normal value (phenol, 3600 cm-1) to 3100 cm-1. Tropolone behaves like a phenol. It forms metallic salts, ethers and esters. It shows strong absorption in the ultraviolet, which changes from neutral to alkaline solution similar to phenol. In the IR the C=O stretching frequency is abnormally low (1615 cm-1). Tropolone undergoes a wide variety of electrophilic substitution reactions.

Eight  electron system. Cyclooctatetraene The molecule is not planar but tub shaped. Therefore,

the molecule will be neither aomotic nor antiaromatic, since both these conditions require overlap of parallel p orbitals. The reason for the lack of planarity is that a

regular octagon has bond angles of 135 while sp2 angles are 120. To avoid the strain, the molecule assumes a nonplanar shape (tub shaped) in which the orbital overlap is diminished. Single and double bond distances are 1.46 and 1.33Å as expected for a linear polyene. It is very reactive, undergoes catalytic hydrogenation, oxidised to aromatic compounds such as benzaldehyde, benzoic acid and phthalic acid, Cl2, Br2 & HBr react with cyclooctatetraene by addition. It undergoes Diels-Alder reaction. The resonance energy was found to be 2.4 kcal mol-1, UV spectrum shows a maximum at 282 nm and the NMR spectrum shows a peak at 5.69, confirming the absence of an induced ring current. It seems certain, there fore, that cyclooctatetraene is nonplanar and nonaromatic. Cyclooctadiendiyne & Benzocycloheptatrienyl Anion

These two compounds are planar, conjugated eight electron systems and so antiaromatic. System with 10 Electrons [10] Annulene There are three geometrically possible isomers of [10] annulene the all cis, the mono trans and the di trans.

In the all cis configuration the bond angle strain is high. For a regular decagon the angles would have to be 144, considerably larger than the 120 required for sp2 angles. Some of this strain is also present in mono trans. In di- trans there is no angle strain but the hydrogen atoms at 1&6 interfere Therefore, [10] annulene is unstable. One way of avoiding the interference between the two inner protons is bridging the 1 and 6 positions. Thus, 1,6-methano, 1,6-oxido and 1,6-imino [10]

annulenes have been prepared. They are stable compounds undergo electrophilic substitution and are diatropic.

For example in 1,6-methano[10] annulene the outer proton are found at  6.9-7.3 where the bridge proton are at -0.5. 1,6-Methano [10] annulene is a stable compound, insensitive to oxygen and heat. Azulene

Azulene may be regarded as a combination of cyclopentadienide anion and tropyliumcation. It possesses a dipole moment of 1.08 D. It is aromatic, confirmed by NMR bands in the region  7-8.2 and C-H stretching band at 3030 and 3086 cm-1 (cf. naphthalene 2994 and 3067 cm-1). The resonance energy is 46 K.Cals mol-1. It undergoes wide variety of electrophilic substitution reaction to give 1- substituted azulene. If 1-position is occupied electrophile attacks the 3-position and if both 1-and 3-are occupied the substitution occurs at 5 position. Reason for the attack at C-1 and not at C-2, is the stability of cannonical structure.

It does not undergo Diels-Alder reaction. It undergoes electrophilic substitution with Br2. Acylation occurs with (CH3CO)2 O & SnCl4 and nitration occurs. In all these cases, substitution occurs at 2-position and substitution takes place in the 7-membered ring. Synthesis

Systems with 14 Electrons [14] Annulene

The four inner protons may interfere as in [10] annulene but in lesser degree. The aromatic nature in confirmed by NMR spectrum with two bands one at 0.00 due to 4 inner hydrogens and the other at  7.6 due to 10 outer protons. The compound is destroyed by light and air. A number of stable bridged [14] annulenes have been prepared.

6-Dihydropyrene. It is a red, crystalline compound which is thermally stable. The NMR and the electronic spectra are in accord with the molecule being a delocalised aromatic system.

It is diatropic and the bridge protons are found far upfield in the NMR spectrum. All the bond distance are  1.38 to 1.40A.

Another way of eliminating the hydrogen interferences of [14] annulene is to introduce one or more triple bonds into he system as in dehydro [14] annulene

[18] Annulene

It is diatropic. The twelve outer protons are found at  8.9 and six inner protons at -1.8. X-ray crystallography shows that it is nearly planar, so that the interference

of the inner hydrogens is not important in annulenes this large. The C-C bond distance are not equal but they do not alternate. There are twelve inner bonds of length 1.38A and six outer bonds of length 1.42A. The resonance energy is 37 kcal mol-1 similar to that of benzene. Hetero-Substituted [18] Annulenes Many hetero-substituted [18] annulenes are possible in which the 6 inner hydrogens are replaced by heteroatoms of these system, the compounds with three bridging oxygen atoms or two bridging oxygen atoms and a sulphur atom have spectroscopic properties resembling [18] annulene. However, those with three bridging sulphus atoms or two bridging sulphur atoms and an oxygen atom, have spectroscopic properties resembling the constituent heterocyclic system. The molecule are non planar due to overcrowding.

Sydnones Mesoionic compounds cannot be satisfactorily represented by Lewis forms not involving charge separation. Nearly all known mesoionic compounds contain five membered rings. The most common are sydnones.

They are stable aromatic compounds undergo aromatic substitution when R is hydrogen. They have large dipole moments, 5-7D.

Synthesis

Homoaromaticity When cyclooctatetraene is dissolved in concentrated H2SO4, a proton adds to one of the double bonds to form the homotrophlium ion.

In this species an aromatic sextet is spread over seven carbon atoms. The eigth carbon is an sp3 carbon and so cannot take part in the aromatieity. NMR spectra show the presence of a diatropic ring current, Hb is found at -0.7; Ha at  5.1; H1 and H7 at  6.4 and H2 to H6 at  8.5. This ion is an example of a homoarmatic compound. It may be defined as a compound which contains one or mare sp3 hybridised carbon atoms in an otherwise conjugated cycle. In order for the orbitals to overlap most effectively, the sp3 atoms are forced to lie almost vertically above the plane of the aromatic atoms. Hb is directly above the aromatic sextet and so is shifted far upfield in the NMR. Homoaromatic compounds of 2 and 10 electrons are also known. Fullerene All of the carbon atoms in buckminsterfullerene are equivalent and are sp2- hybridized; each one simultaneously belongs to one five-membered ring and two benzene-like six-membered rings. The strain caused by distortion of the rings. The strain caused by distortion of the rings from coplanarity is equally distributed among all of the carbons.

Speculation about the stability of C60 centered on the extent to which the aromaticity associatd with its 20 benzene rings is degraded by their nonplanarity and the accompanying angle strain. It is now clear that C60 is a relatively reactive substance, reacting with many substances toward which benzene itself is inert. Many of these reactions are characterized by addition to buckminsterfullerene, converting sp2-hy-bridized carbons to sp3-hybridized ones and reducing the overall strain. 1.3 Essential Requirements of a Chemical Reaction Chemical reactions can not occur autometically. For a reaction to take place smoothly fulfilment of certain requirements (conditions) are essentil as noted below. (i) One of the important requirement that is to be fulfilled for smooth reaction is the presence of a reagent which may be either electrophilic or nucleophilic in nature. It may be mentioned that in polar reactions (which actually happens in majority of organic reactions) ions are not formed by autometic bond cleavage. It is in this context, reagent plays a vital role. Again during bond formation it is only the reagent which brings in the necessary ions-electrophilic or nucleophilic to yield the product. (ii) As we know the reaction is always associated with the cleavage and formation of chemical bonds. Again, breakage and formation of bonds are nothing but the breaking and forming of molecular orbitals. Bond formation involves overlapping of orbitals. Hence it is obvious that a reaction to occur, reacting orbitals must approach each other and overlap. It is known that orbitals and their mutual overlap have strong directional influence. So there must be geometrical factors by which reactants can come close together for a successful reaction. These geometrical factors are usually considered as stereoelectronic requirements for a reaction.

(iii) Another condition which may be considered as the most essential requirement for the reaction to occur is the thermodynamic requirement. According to thermodynamic point of view, every reaction, in principle, is a reversible process and always exists in an equilibrium constant K, as shown below.

A B++ P P 12

where A and B are the reactant and P1 and P2 are the products. The equilibrium constant K, is given by the expression PP  k = 12 ...(1) AB  where terms in the brackets indicates concentrations. From the above it is evident that the reaction, in order to go in the forward direction which means that reaction actually occurred, multiplication of the concentrations of the products must be greater that that of the reactants. But that is only possible if there is a decrease in free energy (G()) or in otherwords product (s) must be stabler than the reactant in the conditions under which the reaction is being carried out. The difference in energy content of the product and the reactant is known as free energy of the reaction (G()). The free energy of the reaction is related to the equilibrium constant as

G() = - 2.30 RT log K ...(2) It may be emphasised that no reaction can occur unless energy is supplied to the reactant(s). The reactant(s) on absorbing the supplied energy, usually termed as energy of activation (G*) get activated and the reaction starts. The activated reactants are normally known as activated complex or transition state of the reaction and the formation of such a transition state is a must for any reaction to occur. The formation of the product is solely dependent upon the stability of the transition state; more stable the transition state, more probable is the formation of the product and hence more is the probability of the reaction to take place. This is because in the transition state or in activated complex reactants have been forced together in such a manner there is no other alternative but to collapse into the products and the free energy change (G*) (energy of activation) has been found to have direct relation in regard to the ease of the reaction, like the overall system, reactants and the transition state remain in equilibrium indicated by the constant K* which is similarly related to free energy of activation as G* = -2.30 RT log K* ...(3) (i) One more significant and essential requirement for a reaction to take place is the kinetic measurement i.e. for smooth occurrence of a reaction there must be

appreciable change in the concentration of the reacting species at suitable intervals of time or in other words the reaction must occur at a measureable rate. Further, the rate of the reaction is related to the free energy of the reaction (G0) as well as to the free energy of activation. According to rate law, the rate of the reaction is either the rate of disappearance of the reactants or the rate of appearance of the product. Hence the equilibrium constant K in equation (I) is the rate of the reaction. Again, as the formation of transition state is the slowest process it should be the rate determining step. Hence K* and k should be equal according to transition state theory. Thus the relation (3) stand as G* = 2.30 RT log K ...(4) Energy Profile Diagrams The energy associated with the structures of the substrates, transition states and the product (s) of a reaction is generally represented by a plot of free energy against the progress of the reaction. This plot is know as energy profile diagram. Both single step and multi steps reactions may be represented by such energy profile diagrams as pictured below.

In the multisteps reaction, there is formation of intermediates. In these reactions, there are more than one transition states each with energy higher than that of intermediates. Such reactions may be looked upon as separate reactions like reactant → intermediate → product and so on. The stage with higher free energy of activation is usually the slower and is therefore rate determining step of the overall reaction. The intermediate must be less stable than the reactant as well as much more less stable than the product. The difference between the transition state and the intermediate is indicated by the depth of ‘well’ – deeper the well, the more stable is the intermediate.

If may be remembered that in multistep reaction there may be more than one transition states and hence more than one intermediates. In general, intermediates are unstable, however, in many cases they may be isolated. The Hammond Postulate, states that an endothermic reaction proceeds through a product-like transition state, while an exothermic reaction proceeds through a reactant-like transition state, suggesting that the transition states do very depending upon the rate of the reaction.

Inspite of such apparent contradictions and complexities, the fact remains that the Hammett plots are linear over a wide range of chemical reactivity (1 :106). The observes deviations are explicable on the basis of a change in reaction mechanism. Competitive reactions It is pertinent to discuss in this connection another class of reaction in which there are formation of more than one products. These reactions are known as competitive or parallel or concurrent reactions. The side reactions may also be included in this category. These reactions are explained on the basis of common intermediate reaction takes different paths having different quantity of energy of activation and yields different products. Among the different products which one would be the major that depends upon the overall nature of the reaction. In the case of irreversible reaction that product predominates which forms faster than the other i.e. in this case rate of the reaction (kinetic) become the controlling factor for predicting the major product. Thus, this type of reaction is termed as kinetically controlled reaction. Again the rate of a reaction depends upon energy of activation-lesser the quantity of energy of activation higher will be rate of the reaction and hence more is the formation of the product irrespective of its stability. Thus in kinetically controlled reaction activation energy (G*) is more important than free energy (G). But when the nature of the reaction is

reversible, after the formation of different products, an equilibrium is set and obviously the equilibrium is inclined towards more stable products. The reaction involving stable species as the major product is commonly termed as theremodynamically controlled reaction. In this reaction the product ratio is governed by free energy (G) not the activation energy (G*). However, it may be noted that the formation of thermodynamically controlled product is always preceded by formation of kinetically controlled product i.e. initially kinetically controlled products are formed which under the reaction condition forms an equilibrium. Therefore, it may be concluded that if the conditions of the reaction do not permit interconversion (equilibrium) among the products kinetically controlled product invariably becomes the major product. Generally, lower temperature favours (low activation energy) kinetically controlled product while thermodynamically controlled product is formed at higher temperature as it requires higher activation energy.

A common example may be cited in this connection. It is known that butadiene forms both 1,2 and 1,4 addition product with bromine. It has been found that during addition of bromine to butadiene a common intermediate is formed and at low temperature (-80 C) 1, 2 product predominates and so it is kinetically controlled product while at higher temperature (50 C) 1,4 product becomes the major hence it is thermodynamically controlled product. The positive charge is at two different carbon atoms in the common intermediate and hence from this intermediate both 1,2 and 1, 4 products are formed. Competitive reaction may also be represented by energy profile diagram as shown below.

Sometimes formation of common intermediate may not take place in competitive reaction. Different products may directly be obtained. Sulphonation of naphthalene may be considered as an example of such reaction. At low temperature -isomer is obtained which is kinetically controlled product while at higher temperature -isomer predominates. Thus,

The energy profile diagram of the reaction may be drawn as shown below.

It is evident form energy profile diagrams of different reactions that these diagrams provide a clear picture of stepwise changes (in terms of energy) taking place in the substrate by gradual absorption of energy supplied till the product is formed. Therefore, the energy profile diagram of any reaction serves as an useful basis for predicting the mechanistic pathway of a reaction which is usually defined as the description of detailed course of an overall reaction-its sequence of steps through which the reactants are converted into products. It may be noted that this decription includes (i) movement of electrons which leads to the breaking and making of chemical bonds and (ii) the spatial relation of atoms associated with the change. Methods of Determining Reaction Mechanism After the discussion on essential requirements and their mechanistic classification a pertinent question that may arise is how to specify the mechanistic path of a reaction. In order to specify a mechanism with reasonable certainity, we have to carry out several experiments because the result of one experiment although may rule out some of the possible alternatives yet may be consistent which more than one mechanisms. Some of the most valuable experiments that are usually undertaken are discussed in sequel. 1. Identification of products: Identification of products is an essential part for specifying the mechanism. The proposed mechanism must account for all the products including side products along with proportion. Incomplete knowledge regarding all the products may lead to incorrect mechanism. An important example in this regard is the Von Richter rearrangement in which nitro group is replaced by carboxylic group in presence of KCN. Initially formation of elemental nitrogen during the reaction as a major product was not realised and hence it was suggested that in this reaction there is simple case of replacement of intro group by cyanide which on hydrolysis yield carboxylic acid.

Subsequently elimination of elemental nitrogen during the reaction has been settled and correct mechanism has been proposed as

Similarly identification of very minor product may give a valuable clue regarding mechanism. Thus, when alky! halide is treated with alkali a small amount of olefin has been isolated along with the major product, alcohol. This suggests that the reaction proceeds through carbocation as intermediate.

2. Characterisation of Intermediates (a) Isolation of intermediates in most of the reactions are stable and hence can be isolated. Most familiar example that may be cited in this connection is the isolation of isocyanate in Hofmann bromamide degradation for the preparation of amines form amide.

Isolation and identification of isocyanate clearly establishes that this reaction proceeds by the migration of organic group (R) from carbon to nitrogen. On this basis mechanism of the reaction proposed as

Another example is the isolation of ketene in Wolf rearrangement- intermediate steps of Arndt Eistart synthesis of higher acid from its lower members. Isolation of ketene is a definite proof for the mechanism suggested. Thus,

Conversion of lower acid to higher homologue is Arndt-Eistart synthesis but the transformation of diazo alkyl ketone to ketene is Wolf-rearrangement. (b) In many reaction intermediates formed are so unstable that they can not be isolated. However they may be characterised by different means. (i) Detection: Carbocations, carbanions and free radicals may be detected by spectral measurements like electron spin resonance (ESR) and Raman spectroscopy. (ii) Trapping: It has been observed that in many cases unstable intermediate may form adduct with some special compound. Thus carbene can be trapped as cyclopropane derivative.

3. Cross-over Experiment: In order to settle between intra and intermolecular i.e. single and two step mechanism a very frequently employed and very useful technique is the cross-over experiment. Crossover experiment is carried with a mixture of similarly constituted but non identical substrate and after the reaction, the products formed are analysed. In the case of intermolecular (two step) reaction, initially there should be the cleavage of bonds with the formation of different reactive species. These reactive species at the final stage may form products containing fragments of both the substrates of the mixture. Most highly illustrative example is the Fries rearrangement. When crossover experiment is performed in most of the cases mixed products have been isolated. Thus,

Formation of mixed (cross) products (a) and (b) clearly suggests that the reaction is intermolecular i.e., two step as shown below.

4. Isotopic Labelling Experiment: Isotopic labelling experiment is one of the most important tools for settling the mechanistic path of reactions. In this experiment a particular atomic centre of special consideration in the substrate is substituted by an isotope and after the completion of the reaction the location of the isotope is traced in the products. An example where such technique has been employed is the Claisen rearrangement. In this rearrangement allyl ether of phenol on heating is transformed into ortho and para allyl ether i.e.,

This nearrangement when carried out with 14C labelled at -carbon atom and the product formed is subjected to ozonolysis there is no formation of active 14 * C O2 is the case of ortho product while active C O2 has been isolated in para product. From these results it is evident that in the case of formation of ortho product inversion in configuration of the allyl group takes place and formation of para isomer does not in configuration of the ally group takes place and formation of para isomer does not occur directly-it is formed through the ortho migration i.e., double inversion which amounts to no inversion occurs during the formation of para product as indicated below.

Another example in which an intriguing problem has been solved by labelling technique is the alkaline hydrolysis of ester. In ester hydroloysis either of the two bonds can undergo cleavage during hydrolysis. On carrying out the 18 hydrolysis with water enriched with H2O , it was observed that the resulting acid contains O18 but alcohol does not. Therefore, it is the acyl oxygen bond that actually undergoes cleavage.

5. Kinetic Isotope Effects: In isotopic labelling experiment it has been assumed that there is difference in the chemical behaviour of different isotopes and so chemical properties of the substrate remain unaltered if an atom is substituted by an isotope. However, in the case of rate of a reaction a certain degree of change has been noted. This change in the rate of the reaction due to the presence of change of isotope has been noted. This change in the rate of the reaction due to the presence of an isotope in place of an atom in the substrate is known as kinetic isotope effect or simply isotope effect. Two types of kinetic isotope effects have been recognised-one is primary and other one is secondary. In the case of primary isotopic effect the bond involving carbon and isotope (while has been replaced in place of hydrogen atom) undergoes cleavage and in secondary effect carbon- isotope bond does not undergo cleavage. In both the cases of isotope effects, rates are always changed than those observed with unlabelled (original) compound. This kinetic effect is a powerful tool in determining the mechanistic route of many reactions. Example of primary effect that may be cited is the formation of alkene form isopropyl bromide in presence of alkoxide. Thus, if hydrogen atoms of CH3

group of isopropyl bromide are replaced by deuterium the rate of formation of propene is substantially reduced.

This large isotope effect clearly indicates that the ratedetermining step of the reaction involves the cleavage of C-H bond and rejects the prevailing opinion that elimination occurs via the formation of carbonium ion i.e.

The correct mechanism of the reaction thus stands as noted below after kinetic isotope effect study.

The decrease in the rate of solvolysis of tertiary butyl halide in aqueous ethanol is a case of secondary kinetic isotopic effect. In this reaction, C-D bond does not undergo breakage but due to decreased hyper-conjugative effect stabilisation of carbocation is decreased causing the lowering in the rate. 6. Stereochemical Effect: The study of stereochemical course of the reaction serves a useful tool in determining the mechanism. Nucleophilic substitution 1 2 1 reaction primarily occurs either by SN or SN . The SN path proceeds through carbocation which is planer and hence chiral substrate produces racemic product while due to backside attack always inverted products are obtained when substitution takes palce through SN2 path. But when the following -bromohydrin

is subjected to alkaline hydrolysis there is retention in configuration in the diol, the product. Based on this observation, the hydroloysis has been explained on the basis of formation of an epoxide as an intermediate by the participation of neighbouring hydroxyl group at -position as depicted below.

Exercise 1. Write a note on (i) Huckel’s theory of aromaticity (ii) Homoaromaticity (iii) Aromaticity of fullerences (iv) Aromaticity of sydnones (v) Aromaticity of [10] annulenes (vi) Aromaticity of [14] annulenes (vii) Aromaticity of [18] annulenes (viii) Aromaticity of azulene (ix) Alternant and non-alternant hydrocarbons 2. Give an account of (i) Hammond’s postulate, (ii) Energy profile diagrams (iii) Intermediate versus transition state 3. Have are the following method usefull to estabilish the mechanism of reaction? (i) Product analysis (ii) Crossover experiments (iii) Kinetic methods (iv) Stereochemical studies (v) Kinetic isotopic effect (vi) Substituent effect 4. List out the rules for the nomenclature of (i) Alicyclic compounds (ii) Bicyclic and tricyclic compounds 5. Explain nomenclature of heterocycles with suitable example.

Unit - II 2.1 Stereochemistry Isomers with the same MF and also identical orders of attachment of atoms/groups within their molecules differ only in the relative positions of those atoms or groups in space, they are known as stereo isomers (the later phenomenon is known as stereoisomerism). Concept of Chirality An object that is not superimposable on its mirror image is called chiral (Greek: cheir, hand*). The property of an object that makes it nonsuperimposable on its mirror impage is known as chirlity. An object that lacks chirality, i.e. whose mirror image is superimposable on the original object is called actiral (“not chiral”).

An asymmetric carbon atom is the common example of a chirality centre. A stereocentre or a stereogenic atom is any atom that leads to chirality (and hence enantiomerism). So, a stereocentre or a stereogenic atom does not have to be a carbon atom always. It may be even N as in quaternary amonium salt with four different groups bonded to N. Even enantiomers of tetrahedral Si, P, Ge compounds have been isolated.

Principles of Symmetry Elements of symmetry. The geometric elements of the molecule generating symmetry operations are called symmetry elements. These may be a point, an axis or a plane through which the operations are performed. The complete information of the symmetry of the molecule can be described in terms of symmetry elements. For a single molecule, there are five symmetry elements correspond to symmetry operations. These are: (i)

Indentity E (ii) Rotationa axis or proper axis of symmetry (Cn) (iii) Plane of symmetry (iv) Centre of symmetry (v) Alternating axis of symmetry or Improper axis of symmetry. (i) Identity (E). In identity operation no change is made in the original molecule. We can say identity is the operation of not doing anything. When we do not do anything we leave the system unchanged and identical to the original system.

(ii) Rotation axis or proper axis of symmetry (Cn). If an imaginary axis can be constructed in a molecule around which the molecule can be rotated through an angle, say , to get an indistinguishable configuration, the molecule is said to possess a rotation axis. (iii) Plane of symmetry (). An imaginary plane that bisects molecule in such a way that the two parts are mirror images of each other. This element of symmetry is represented by symbol (). For example, (iv) Centre of symmetry (i). This is such a point through which if a line drawn meets identical atoms at equal distances from the point in two

opposite directions. The centre point is known as a centre of symmetry. The symbol used to indicate inversion centre is i. (v) Alternating axis of symmetry (Sn) or Improper axis of symmetry. When a molecule has a n-fold alternating axis of symmetry is rotated through an angle 360/n about this axis and then followed by the reflection in a plane perpendicular to this axis, the molecule is indistinguishable from the original structure. Optical Activity-Relation to Chirality and Symmetry Elements We have seen that asymmetric molecules lack all elements of symmetry except a trivial axis i.e., there is no simple axis of symmetry, plane of symmetry, alternating axis of symmetry and centre of symmetry. A dissymmetric molecule has simple or proper axis of symmetry but lacking alternative axis of symmetry. Optical Activity The light whose vibrations occur in only one plane is called plane polarized light. The substances which rotate the plane of polarized light are said to be optically active and this property is known as optical activity. The instrument used to measure the angle of rotation of plane polarized light caused by an optically active substance is called polarimeter. When the sample tupe (T) is filled with the solution of an optically active substance (enantiomer), the plane of the polarization of light has been rotated and observer will not detect any light. In order to detect maximum brightness of light, the observer will have to rotate the axis of analyzer (A) in either clockwise or anti-clockwise direction If the scale mounted on analyzer (A) is rotated in a clockwise direction, the rotation  measured in degrees is said to be (+) and if anticlockwise, the rotation is said to be (-). An optically active substance that rotates the plane of polarized light to clockwise direction is said to be dextrorotatory (Latin : dexter, right) and that rotates in anticlockwise is said to be laevorotatory (latin : laevus, left).

Diagram of polarimeter with sample tube containing an optically active substance

The specific rotation, []D, is given by following relationship:

[]D = Observed rotation() Length(l ) of the polarimeter tube in dmConc  gms per. (c) mlof the substance in

20  = D l c Enantiomers (i) isomers which are the non-superimposable mirror images of each other are enantiomers. (1) Enantiomers have identical physical properties like m.p., b.p., density, refractive index, etc., but they differ in their action on plane- polarized light. One of the enantiomers rotates the plane polarized light to the right (dextrorotatory) and the other enantiomer rotates the plane of polarized light to the left (laevorotatory). (2) Enantiomers have idetical chemical properties except their action towards optically active reagents. The Racemic Modification A mixture of equal parts of enantiomers is called a racemic modification or a racemic mixture. Such racemic modifications are optically inactive, because the rotation caused by molecules of one isomer is cancelled out by an equal and opposite rotation caused by an equal number of molecules of its enantiomer. When a chiral compound is synthesized from achiral reactants, the product is always of the racemic variety. Fisher Projection Formula

In this representation, the molecule is shown as a simple line drawing. The steric projection formula is first drawn vertically in such a way that the horizontal groups project towards the viewer. The entire molecule is then flattened on the plane of the paper in the form of a line drawing. To convert the Fisher projection formula into a steric projection formula, pull the horizontal groups above the plane of the paper and push the top and bottom groups below the plane of the paper. Fisher projection formulae are extensively used in carbohydrate chemistry.

Saw-Horse Representation In this representation, the molecule is viewed from an inclined angle as shown below. In structure, the C-C bond could be rotated around its bond axis by 180 to obtain a new conformation. Such saw-horse representations are extensively used to depict the orientation of atoms and groups in.

Newman Projection Formula If you rotate the saw-horse representation in such a way that the carbon at the front eclipses the carbon at the back, you get the Newman Projection Formula. This representation is very convenient to depict the relative orientation of groups across the C-C bond. Newman projections are ideally suited to describe conformational aspects across such  bonds. The angle sustained by one group on the front carbon to another group on the back carbon is called the dihedral angle (teta, ). The newman projection formulae are extensively used in spectroscopy and conformational analysis. Note that the saw-horse projection of is depicted in as newman projection formula. The trans orientation of the two bromine atoms is clearly seen in Newman projection. In addition, note the R1 groups lie together on one side and R2 groups lie on the other side. The developing  bond retains this relative orientation all along, as seen in the final structure of the product.

Interconversion of Fischer projection saw-horse and Newman projection formula The horizontal groups (b, c, x, z) are in front of and the vertical groups (a, y) are behind the plane of the paper. In order to convert them into the sawhorse formulae, the bottom chiral centre is written at the front and the top one at the rear while the substituents are placed in front (up) and behind (below) as implied in the fischer projection. The structures (IIIa) and (IVa) result which are direct translation of the structures (III) and (IV)

respectively. The front carbon is next rotated through 180 in each case in given the conventional staggered sawhorse formulae (IIIb) and (IVb). Conversion of the sawhorse formulae into the Newman projection formulae (IIIc) and (IVc) is easy. Direct translation of the fischer projection into a Newman projection can likewise be done through the intermediate eclipsed conformations (IIId) and (IVd) which are subsequently transformed into the usual staggered Newman projection formulae (IIIc) and (IVc) by rotating the front carbon.

Racemic Forms and Enantiomeric Excess (EE) If a sample of an optically active substance contains a single enantiomer is said to be enantiomerically pure or an enantiomeric excess of 100%. For example, an enantiomerically pure sample of (+)-Tartaric acid  20 shows a specfic rotation of +12.7 i.e.  D =+12.7 (H2O). On the other hand, if a sample of (+)-Tartaric acid shows a specific rotation less than +12.7 but greater than zero degree, such a sample is said to have an

enantiomeric excess less than 100%. Hence, enantiomeric exess (ee) may be defined as follows: Observedspecificrotation %Enantiomeric excess = 100  Specificrotation of pureenantiomer Configuration We have represented the two enantiomers of lactic acid as I and II. Arrangements of the atoms or groups in space for each enantiomer define their configurations. The actual arrangement in space of the atoms of a stereoisomer (i.e., absolute configuration) can now be determined by using Buhviet’s X-ray analysis, but it is not essential to determine the absolute configuration of every optically active compound. It is usually sufficient to know the configuration of a compound and relate it to that of an other compound. If a reaction does not involve the breaking of a bond at a chiral carbon, the configuration about that chiral carbon is retained. Relative Specification of Configuration ‘D’ and ‘L’ Notation Procedure for assigning D and L configuration. It involves following steps: (i) Orient the main carbon chain in a vertical line with priority group (according to IUPAC nonmenclature) at the top. (ii) Arrange the substituents at chiral carbon atom on horizontal line projecting towards the observer.

(iii) Now on examination if the main substituent (e.g., OH, NH2 etc) is on the right hand side of the observer (on horizontal line), the configuration is assigned D notation without indicating any sign of optical rotation and if on the left hand side L configuration is given. For example,

(iv) The D and L notation can also be extended to multiple asymmetric (chiral) carbon containing compounds (e.g., in carbohydrates). In such cases bottom chiral carbon containing structure is compared to corresponding D or L forms of glyceraldehyde. For example,

The compounds having D or L configurations are arbitarily classified as D and L family of chiral compounds. Limitation. D,L-nomenclature indicates configuration at only one chiral centre. It is therefore not satisfactory for assigning configuration for compounds containing more than one chiral centre. Specification of Configuration ‘R’ and ‘S’ Notation* Chan, Ingold and Prelog have proposed a procedure to specify a particular configuration in a simpler and more convenient way than by always drawing its picture. This procedure involves the following steps: Step 1. The four atoms or groups of atoms attached to the chiral carbon atom are assigned Priorities in accordance to the following sequence rules: (a) Sequence rule 1. when the four atoms attached to the chiral carbon atom are all different, priority depends on atomic number. The atom of higher atomic number gets the higher priority. Thus, the priority in the compound bromo-chloro-iodomethane (C H Cl Br I) is I, Br, Cl, H. When isotopes of the same element are attached to a chiral carbon, the isotopes with higher mass number gets priority. -Deuterio ethyl bromide [CH3CH(D)Br] for example, has the priority sequence of Br, CH3, D, H. In general, when the substituents are attached to chiral carbon, the decreasing order of priority is:

I > Br > Cl > SH > F > OH > NH3 > CH3 > D > H (b) Sequence rule 2. If rule-1 fails to decide the relative priority of two groups of atoms attached to a chiral carbon atom (e.g., the two groups may be –CH3 and –CH2CH3: carbon is attached directly, in either case, to the chiral carbon), the priority may be determined by comparing the next atom in the group. If it is still not possible to decide the priority of the two

groups, the comparison may be continued to the next atom, and so on.

CH2CH3

CH3CHCl Thus, the priority sequnece in sec-butyl chloride , is Cl, C2H5, CH3, H(C2H5 has priority over CH3 because the second atoms in C2H5 are C,H,H whereas in CH3 are H,H,H). Therefore, when two of the atoms directly attached to the chiral centre are identical, the priority is decided by considering the next closest H C 3 CH H3C atoms. For example, has higher priority than CH3CH2CH2-, CH3CH2- has higher priority than CH3- and CH3CH2O- has higher priority than HO-. (c) Sequence rule 3. A double or triply bonded atom is equivalent to two or three such atoms. H Thus between the groups, C O (O, O, H) and –CH2OH (O, H, H) the former (CH = O) will have priority in the compound glyceraldehyde,

OHCCH(OH)CH2OH. Step 2. When the priorities of the four atoms or groups attached to an aasymmetric or chiral carbon have been decided, the molecule is visualized so that the atom or group of the lowest priority is directed away from us. On looking at the arrangement of the remaining atoms or groups of atoms in decreasing order of priorities, if the eye travels in a clockwise direction the configuration is specified as R. If the eye travels in the anticlockwise directoin, the configuration is specified as S. The following examples will illustrate the above procedure of specifying R and S notation to compounds containing an asymmetric or chiral carbon atom.

(These structures are also called steering wheel projections) It may be pointed out that the direction or rotation of an optically active compound is independent of the (R)- or (S)- configuration of the compound. Thus, a complete description of an optically active compound must include both the configurations (R or S) and the direction of rotation (+ or -) prefixes. For example, R-(-)-sec-butyl chloride. Such structures can be constructed on Fischer projection formulae (Palanar structure) and equivalent structures can be constructed for R-S notation, if necessary. The prefix (RS) is used to denote a racemic modification. For example, (RS)-sec-butyl chloride. Problem 1. Designate R or S configuration to following compounds-

Answer. (i) The order of priorities is NH2 > COOC2H5 > COOH > H

(ii) The sequential order of priorities is Cl > H2C=CH->CH3CH2>H. The configuration of (ii) is, therefore, R.

(iii) The order of priority is Br > CH2Cl > CH(CH3)2 > CH3. The sequence of decreasing priority order is counter clockwise. Therefore, configuration of (iii) is S. Problem 2. Assign R and S configuration to following structures:

Answers:

(i) Priority order HO > COOH > CH3 > H, hence, it has R configuration. (ii) Priority order HO > CHO > CH2OH > H, hence, it has S configuration. (iii) Priority order HO > C2H5 > CH3 > H, hence, it has S configuration. Compounds with two Stereogenic Centre or two Asymmetric/Chiral Carbon The two chiral carbons (C*) may be dissimilar (when the atoms or groups attached to one chiral carbon atom are different from those attached to the other) or similar (when the atoms or groups attached to the two chiral carbon atoms are identical). For example, The stereochemisty of these two representative compounds is described below: 1. Stereochemistry of 3-chloro-2-butanol. It contains two dissimilar chiral carbon atoms (C*), as shown below:

(I) and (II) constitute a pair of enantiomers. Obviously, (III) and (I) are stereoisomers but not enantimoers. Similarly, (III) and (II) are also stereoisomers, but not enantiomers. steriosomers which are not mirror images are called diastereomers.

Distinction Between Diastereomers and Enantiomers The distinction between diastereomers and enantiomes is given Distinction between Diastereomers and Enantiomers S.No. Diastereomers Enantiomers 1. These do not have mirror image These are mirror images of each relationship. other. 2. Diastereomers have different Each enantiomeric pair has similar physical properties. physical properties. 3. Due to different physical Due to similar physical properties, properties, these can be separated these cannot be separated by physical by fractional distillation, methods like fractional distillation and fractional crystallization etc. 4. They may have rotation in the Enantiomers have rotation in same direction but to different opposite direction but to same extent. extent. 5. These may or may not be optically These are always optically active. active. Specifying R-S Configurations on Fischer Projection Consider the example of tartaric acid (I) to assign R-S notation at the two chiral carbons C-2 and C-3 on Fischer projection.

For configuration at C-3 in structure (I), fix upper half part and then rotate three substituents at chiral carbon C-3 to get stereochemically equivalent structure.

Hence, structure (I) has 2R 3R notation at chiral carbon C-2 and C-3 respectively. The steps involved in above operation or for any such compound are: (1) Draw Fischer projection (as per guidelines given earlier) in such a way that substituent of lowest priority is at the top or bottom of the vertical line. (2) Assign the order of priority to each substituent or group (as 1, 2, 3, 4) on chiral carbon atom as per Cahn, Ingold and Prelog sequence rules, given under sec. 6. 7. 2. (3) Observe the order of decreasing priority of other three substituents. If this is clockwise, the configuration is R (rectus), and if anticlockwise, it is S (sinister). Problem 3. Assign R-S notation to chiral carbon C-2, C-3 in the following structures:

Answer: (a) 2S, 3R (b) 2R, 3S (c) 2S, 3S (d) 2R, 3R Problem 4. Assign the configuration to the following structures of 2, 3-dibromobutane.

Answer: (i) 2S, 3S (ii) 2R, 3R (iii) 2S, 3R

Erythro and Threo Nomenclature (Notation) of Configurations Erythro- and threo- notations have been derived from the structural resemblance to two sugars, erythrose and threose, having following structures: On reviewing above structures we conclude that: (i) isomers having identical substituents or groups on opposite side are called threose forms.

Resolution The process used to separate a racemic modification into enantiomers is called resolution. Some important methods used to resolve a racemic modification into enantiomeric forms are: (a) Biochemical method. When certain micro-organisms are allowed to grow in racemic compounds, they prefer to take up one of the enantiomers. When penicillium glaucum, for example, is added to racemic tartaric acid, it consumes only (+)-tartaric acid for its growth leaving (-)- tartaric acid unused. Thus, (-) tartaric acid can be isolated in a pure state. Limitations. (i) It leads to the destruction of one of the enantiomers. (ii) The recovery of the enantiomer is often very laborious. (b) Mechanical separation. Sometimes, a racemic modification crystallises out from a solution to produce a well-defined mixture of

crystals of the (+)- and (-)-forms. These crystals, being enantiomeric, can be separated by “hand-picking” or forceps with the help of a lens. Pasteur, discovered enantiomerism through such a resolution of racemic sodium ammonium tartrate. Limitations. This method is also laborious and limited to only those cases in which the identification of two enantiomeric forms of crystals is possible by such means. (c) Chemical method. The underlying principle of this method is that the racemic modification is converted by an optically active reagent into a mixture of diastereomers which can then be separated. Suppose the racemic substance under examination is an acid A, consisting of an equimolecular mixture of (+)-A and (-)-A. It is made to react with an optically active base, say (-)-B. Two salts namely (+)-A (-)-B and (-)-A (-)- B will be formed. These salts, being diastereomers will difffer in physical properties such as solubility. These salts (+)-A (-)-B can, therefore, be separated from one anonther by fractional crystallisation and can be easily converted into (+)-A and (-)-A acids on treatment with strong mineral acids*. For example, ()-tartaric acid on treatment with the optically active base, (-)- cinchonidine** forms (+)-acid (-) –cinchonidine and (-)-acid (-)- cinchonidine salts. The two salts can be separated from one another by fractional crystallization. The (-)-acid (-)-cinchonidine salts, being less soluble, separates out first. These salts can be reconverted into the corresponding (+)-and (-)-acids by treatment with dilute sulphuric acid. A general scheme of separation is outlined below:

These diastereomers are separated from one another bhy fractional crystallisation. These salts can be reconverted into the corresponding (+) and (-) bases by treatment with strong base.

(d) Selective adsorption in chromatographic column. In this method resolution of the racemate is achieved by passing its solution over a column of finely powdered starch as adsorbent. The surface of the adso9rbent selectively absorbs one enantiomer and the solution comes out first if container is richer in one enatiomer. For example, () mandelic acid is separated by using starch as adsorbent in chromatographic column. Asymmetric (Stereogenic Centre) Synthesis Synthesis of dissymmetric or chiral compounds from non- dissymmetric or achiral reagents is called asymetric synthesis. Direct reduction of pyruvic acid gives the racemic modification of lactic acid, as expected. However, when pyruvic acid, pre-esterified with an optically active alcohol [say, (-)-menthol*], is reduced and the resulting alcohol hydrolysed, we get mainly (-)-lactic acid.

When benzaldehyde is treated with hydrogen cyanide in the presence of an optically active enzyme emulsin, the main product is (-)-mandelic acid.

Thus, we find that we have achieved the laboratory synthesis of optically active dissymmetric (chiral) compounds from optically inactive non-dissymmetric compounds under the influence of suitable optically active substances-(these, of course, get removed subsequently). The synthesis of the type described above is known as asymmetric synthesis as it leads to the formation of asymmetric or dissymmetric compound showing optical activity. Thus, asymmetric synthesis is the synthesis of an optically active dissymmetric ccompound from non-dissymmetric molecule, under the influence of some optically active substance. It is interesting to note here that most of the dissymmetric (chiral) compounds found in nature (e.g., amino acids, carbohydrates, proteings, alkaloids, etc.) exist in optically active forms. This is possibly due to the fact that they are synthesized in nature under the influence of other optically active species like enzymes. In other words, the biological syntheses are mostly asymmetric syntheses. Walden Inversion If an atom or a group of atoms directly attached to an asymmetric carbon atom is replaced by another atom or group of atoms, the configuration of the product is sometimes found to be different from that of the parent compound. This phenomenon, which involves the inversion of configuration during a reaction, is called Walden inversion after the name of Walden, the discoverer of this phenomenon. Occasionally, Walden 2 inversion is known as Optical inversion also. For example, SN substitution of (-)-2-bromo-ocatane with alkali.

It may be stressed here that the inversion of configuration may or may not lead to a change in the direction of rotation. Change, if any, is incidental only. Retention and Racemisation We have seen above how Walden inversion takes place when an alkyl halide containing an asymmetric/chiral carbon reacts with a nucleophile (say, a base) by the back-side attack. Consider now the reaction of a chiral alkyl halide [say, (S)-3-Bromo-2, 3-dimethylpentane] (I) with a mild base (say, solvent ehanol). We shall learn in due course that the reaction is a 2-step reaction involving the intermediate formation of a carbocation(IA), as shown below in the figure.

The carbocation (IA), which is planar and achiral, is susceptible to attack from both faces. If the attack takes place form the front side, the chiral product has the same configuration (S) as I, i.e., there is retention of configuration in going from I to II. However, when ethanol attacks IA from the backside or rear side, the product is III with configuration (R) opposite to that of I, i.e., there is inversion of configuration in going from I to III. Apparently, II and III are enantiomers. If, both II and III are in equal amounts, the product would naturally racemic. A process that gives both enanitomers of the product in equal amounts during the reaction of the chiral starting material is called racemisation. The retention of configuration is the formation of the product (in a stereochemical reaction) with the same configuration as that of the reractant. As diastereomers, geometric isomers have different physical properties*such as melting points, boiling points, solubilii\ties, dipole

moments, densities. refractive indices, etc. They differ in adsorption capacities also on materials commonly used in chromatography. Pairs of geometric isomers should, therefore, be capable of separation by techniques of fractional distillation, ftactional crystallization or chromatography. Assigning Configuration to Geometric Isomers It may be asked at this stage how we assign configurations to geometric isomers. In other words, how do we know, for example, whether maleic acid (m.p. 130C) is the cis- or trans-isomer. There are no hard and fast methods for assigning configurations to geometric isomers. We often make use of differences in their physical and chemical properties to assign configurations to geometric isomers, as illustrated below: (1) Chemical differences. Maleic acid (m.p. 130C) dehydrates, on heating, to maleic anhydride but fumaric acid (m.p. 287C) does not from the corresponding anhydride under similar condition. On this basis, maleic acid was assigned the cis-configuration and fumaric acid the trans- configuration, it being explained that the –COOH groups in fumaric acid (trans-) were too distant to undergo dehydration.

This difference in their chemical behaviour was thus used in assigning configurations to this pair of geometric isomers. (2) Dipole moment difference. 1, 2 – dichloroethene (b.p. 60C, m.P. - 80C) has the dipole moment, , equal to 1.85D, whereas 1, 2- dichloroehtene (b.P. 48C, m.p. -50C) has no dipole moment. On this basis, 1, 2-dichloroehene (b.p. 60C) was assigned the cis-configuraion, and 1, 2-dichloroethene (b.p., 48C) the trans-configuration. It was understndable also because dipole moment is a vector quantity. In the trans isomer the bond moments of C-Cl bonds cancel out but not in cis-isomer.

In general, cis-isomer always has higher dipole moment than the trans-isomer. This physical property is also used in assigning configuration to geometric isomers (where applicable). (3) Boiling point and Melting point differences. Cis-isomer, being more polar, should have the higher boiling point and it is so (the data given above for two-2-butenes and 1, 2-dichloroethgenes). Cis-isomer having lower symmetry would fit into the crystalline lattice more poorly. Consequently, the cis isomer should have lower melting point that the trans-isomer. This is actrually so, as evident from the data given above for different pairs of cis-trans isomerrs. Thus, the differences in the melting and boiling points can also be used for assigning configurations to geometric isomers. However, it must be pointed out that there are quite a few exceptions also to this generalisation, cis-1, 2-Di-iodoentene, for example, has a lower b.P. than the trans-isomer. E-Z System of Nomenclature for Cis-Trans Isomers Only disubstituted alkenes have so far been taken as examples of compounds showing geometric isomerism, but tri- and tetra substituted alkenes also show geometric isomerism provided each doubly-bonded carbon carries non-identical atoms or groups. In general (I) should show geometric isomerism when (i) a, b, c and d are all different or (ii) one of these is H, or (iii) two of these (one on each of the doubly bonded carbon) are H. The following tri- and tetra substitued alkenes (II to IV) for example, show geometric isomerism.

How do we name such geometric isomers? The prefixes cis and trans will not work here because it is difficult to find the reference points in such compounds. The following procedure is followed in naming such compounds: (1) Arrange the atoms or groups attached to each doubly bonded carbon in the Cahn-Ingold-Prelog priority sequence (mentioned earlier under R and S configurations), sec. 6. 7. 2. (2) Choose the atom or group with the higher priority on each doubly bonded carbon. If the atoms or groups of higher priority on each carbon are on the same side of the molecule, the letter Z (German zusamen, means together) is used to denote the configuration of such an isomer. When the atoms or groups of higher priority on each carbon are on the opposite sides of the molecule, the letter E (German entgegen, means opposite) is prefixed before the name to indicate configuration. The following examples illustrate this procedure of naming geometric isomers:

If the alkene has more than one double bond, the stereochemistry about each double bond should be specified, as illustrated in the naming of the following diene, 3, 7-dichloroocta-2, 5-diene.

Exercise. 3, 7-Dichloroocta-2, 5-diene is capable of existing in several geometric isomers. Only one geometric isomer has been named

above under the E-Z system. Draw the structures of the other possible geometric isomers and name them under the E-Z system. Note: It is always optional to use E-Z names rather than the names with cis-trans-notations. E-Z name is, however, required whenever a double bond is not clearly cis- or trans. Tri- and tetra substituted double bonds are better named under the E-Z system and not in the cis-trans system. Problem 1. Designate E, Z notation to each of the following:

Stereospectific Reaction Stereopecific reaction is a reaction in which each stereoisomeric reactant (diastereomer or enantiomer) leads to a different steroisomeric product (diastereomer or enantiomer) under identical conditions. For example, iodide-induced debromination of both diastereomeric 2, 3-dibromobutanes give different products. Meso-2,3-Dibromobutane gives trans-2-butene and d, 1-2,3- dibromobutane gives cis-2-butene, respectively.

Stereoselective reaction is the reaction in which a compound produces diasteromeric products in unequal amounts. It is interesting to note that bromination of trans-2-butene gives meso-dibromide and that bromination of cis-2-butene gives racemic modification (pair of enantiomers). This can also be explained by the addition of bromine on the cyclic intermediate bromonium ion. Thus, the reaction is stereoselective.

Optical Isomerism of Allenes Spiranes and Related Compounds (Axial Chirality) In the spatial arrangement of the cumulative double bonds of allene, the four subsituents of the allene grouping are situated at the apexes of an imaginary tetrahedron, elongated. The following points may be noted.

In an allene, the central carbon atom atom is sp hybridized and linear, and the two outer carbon atoms are sp2 hybridized and trigonal. The central, sp hybrid carbon atom must therefore, use different p orbitals to form the pi bonds with the two outer carbon atoms. The two unhybridized p orbitals on a sp hybrid carbon atom are perpendicular, so the two pi bonds must also be perpendicular (scheme 1.113).

In allene (I, 1,2-propadiene, symmetry group D2d) the C=C=C is apotential chiral axis. The planes defined by H(C1)H and H(C3)H are mutually perpendicular. Allene itself is achiral since it has two planes of symmetry. In order to generate chirality, the two planes of symmetry must be eliminated. When unlike substituents are added at each end of the C=C=C unit, the substituted allene becomes chiral. This is so in 2,3-pentadiene (scheme 1.113) substituent at one end (H and CH3 ; H  CH3) and the other end (H and CH3

; H  CH3). An allene with unlike substituents only at one end as in (scheme 1.113) leaves one symmetry plane and the allene is achiral. The allene (IV, scheme 1.113) with all the four end groups different (this is also so when three end groups are different) loses the C2 axis and becomes asymmetric belonging to C1 point group.

The replacement of the double bond in an allene by a ring gives alkylidenecycloalkanes (sometimes referred to an hemispiranes) does not alter the basic geometry of the system of allenes and suitably substituted compounds, therefore, exist in optically active form e.g., (I and II scheme

1.115). Related compounds in which sp2-carbon is replaced by nitrogen, e.g., compound (III, scheme 1.115) has also been obtained as enantiomers. The replacement of both double bonds in an allene by ring systems gives a spiran; appropriately substituted compounds have been obtained in optically active forms (IV and V scheme 1.155a).

Optical Isomerism in Biphenyls (Atropisomerism) In the crystal, both benzene rings of biphenyl lie in the same plane (I, Scheme 1.117). However, in solution and vapour phase the two rings are twisted with respect to each other by an angle of 45 due to steric interactions between the 2,2 and 6, 6 pairs of hydrogens (II, Scheme 1.117). These interaction effects are further enhanced by ortho substituents larger than hydrogen so that: The rotation about the bond linking the two phenyl rings does not occur due to steric hindrance between the bulky ortho substituents. The two rings lie in different planes which are perpendicular, to make it impossible for the molecule to achieve a conformation in which the two aromatic rings are coplanar and this conformation has a plane of symmetry and this rules out chirality. This is so in a symmetrical structure shown for example by the planar formula of O, O difluorodiphenic acid (see scheme 1.120). Resolvable (chiral) biphenyls must contain two different ortho substituents on each ring and these make each ring unsymmetrical (H is taken as a substituent) and two rings are held in perpendicular planes.

Each ring in a biphenyl individually represents a plane of symmetry irrespective of ortho substituents (and other groups). Consider the biphenyl which can be schematically represented (III scheme 1.117) depicting the rings in perpendicular planes with two bulky ortho substituents (A) and (B) on each ring (A  B). Such a biphenyl is chiral since nither of these planes can bisect the other into two equal halves. The bipheyl (III, scheme 1.117) has a mirror image (scheme 1.118) and can be resolved into its enantiomers and each enantiomer is stable indefinitely. The nitro and carboxylic groups are so bulky that they cannot pass by each other.

None of the rings should be symmetrically substituted, so that the molecule cannot have a plane of symmetry. Thus, the biphenyl (scheme 1.118) is chiral (A  B in either pair, COOH  NO2 of the ortho sustituents. The biphenyl (scheme 1.119) is, however, achiral. In this case e.g., ring (II) is symmetrically substituted (A = B = COOH). A plane drawn perpendicular to ring, (II, scheme 1.119) contains all the atoms and groups of ring (I) in it, hence it is a plane of symmetry and since it bisects the plane of ring B into two equal halves, thus the biphenyl (scheme 1.119) is achiral.

Atropisomerism The chirality in biphenyls is generated by restricted rotation around a single bond provided each ring has an appropriately substituent pattern. Isolable stereoismers resulting from restricted rotation about single bonds are called atropisomers while rotamers are stereoismers oobtained by rotation about a single bond. The term atropisomer is derived from the Greek “without turning.” Atropisomers may be configurationally stable at room temperature when the hindrance to rotation may be rather severs. Racemization can take place when the sizes of the ortho-substituents are such that these can slip past each other and the two rings become co-planar. Nomenclature of Compounds with (Stereoaxis) Axial Chirality The molecule can be viewed from either end of the steroaxis to give the same descriptor. The near groups are given priority over far groups. For better visualization it is always better to put the groups nearest the view direction on a thick line (horizontal or vertical). Thus in the projection formula of (S)-2, 3-pentadiene (scheme 1.128), the horizontally placed, (nearest the view direction) CH3 and H are to be numbered 1 and 2 and the remaining vertically placed (rear) ligands are simply assigned priorities according to sequence rules i.e. CH3 and H are numbered 3 and 4 respectively. The sequence 1 → 2 → 3 gives the configurational descriptor S (anticlockwise).

Spiranes and Alkylidene-Cycloalkanes These compounds possessing axial chirality are assigned configuration descriptors in the same way as discussed for allenes. As in allenes, the interchange of the two germinal groups in these molecules also leads to enantiomers (II compared to I, scheme 1.131).

Biphenyls In the case of biphenyls, however, it is important to note that the four ortho- carbons are sequenced properly according to CIP rules. Thus in the biphenyl (scheme 1.132) in the left ring the sequence is C-2> C-6> (OCH3 > C-H) while in the other ring C2 > C6 (N > C) and therefore, configuration is S when the biphenyl (scheme 1.132) is viewed from either direction.

When in a biphenyl the C2 and C6 in a ring are attached to identical atoms, the prioeity order of the ortho carbon atoms is then determined through exploration around the ring or side chain. Thus in the biphenyl (scheme 1.133) the 2-H adjacent to 3-Br precedes 6-H.

Conformations of Cyclohexane (Conformational Analysis) The importance of Baeyer strain was first appreciated in 1890 by Sasche, who pointed out that two non-planar models of cyclohexane could be constructed in which all the bond angles can be 109-28’, so that the systems were free of Baeyer strain. One of these was a fairly rigid form, shaped roughly like a chair and the other was a flexibel from whose most symmetrical form was shaped like a boat. (a) The Chair Conformation of Cyclohexane The following points may be noted. Cyclohexane molecule exists predominantly in a non-planar, puckered conformation the chair conformation. All bonds are staggered therefore, Pitzer strain is minimized. However, a gauche butane like interactions between neighboring methylene groups lead to steric strain.

The bond angles are not exactly 109.30’ but 111, a value close to that in acyclic alkanes. The dihedral angles  are not exactly 60, but these are around 56 causing a slight flattening of the ring. The Boat conformation of Cyclohexane The following points may be noted In the boat form of cyclohexane there is complete eclipsing of the hydrogens attached to the carbon atoms forming the “side” CH2-CH2 bonds (shown for one side in III), and the Newman projection shows two eclipsed butane units. Thus the two bonds labeled 0, 0 in (IV) are completely eclipsed. The “inside” hydrogens on C1 and C4 (“flagpole hydrogens”) interfere with each other sterically in transannular interaction (V) and there is a second factor which leads to instability for boat form in comparison to chair. The “flagpole” hydrogens lie only 1.83 A apart than their sum of van der Waals radii 2.5 A.

The Twist Boat Conformation of Cyclohexane The three forms of strain reflect largely on the energy of a conformation in a cycloalkane are bond angle, eclipsing (torsional) and transannular (across the ring) strain. The chair conformation is at the minimum energy possible for cyclohexane system being free from bond angle and eclipsing strain.

The only steric is due to gauche-butane like interactions between neighboring methylene groups. The boat conformation is a higher-energy conformation due to eclipsing on its “side”, carbons and due to transannular interaction between flagpole hydrogens. The boat conformation is somewhat stabilized by moving apart the flagpole hydrogens. The new conformation called “twist boat” which is realized has minimized transannular interactions between “flagpole” hydrogens and at the same time torsional strain between the pair of side carbons of the initial boat are also relieved (scheme 4.23). The symmetry of the twist boat is reduced and the molecule is chiral.

Conformational Analysis of Cyclohexane One chair conformation of cyclohexane can be easily converted into an alternate chair conformation.

Equatiorial and Axial Bonds in Chair Form of Cyclohexane The twelve C-H bonds in the chair form of cyclohexane are of two types. Six of these are parallel to the three-fold axis of symmetry of the

chair. These are represented by vertical lines in the plane of the paper and are designated as axial (I). The remaining six bonds are inclined at an angle of 109.28’ to the three-fold axis and are described as equatorial. Thus following points may be noted. Of the six axial bonds three are above (up) relative to the mean plane of the ring while three are down (below). Thus, the molecular model of cyclohexane can stand firmly on the table by the three upper or the three lower hydrogens (I). On each face of chair conformer of cyclohexane there are three axial hydrogens and their orientation (up or down) alternates form one carbon atom to the next (1).

At room temperature cyclohexane interconverts rapidly to a mirror image chair conformation. As one chair form converts to the other, often referred to as ring inversion or ring flip, all the equational hydrogen atoms become axial and all the axial hydrogens become equatorial without losing their identity as up or down (scheme 4.26).

Conformations of Methylcyclohexane

Two gauche butane interactions between the axial methyl group and the two ring C-C bonds (see arrows) destabilize the axial conformer while no such interactions exist when the methyl is equatorial. Larger groups Compete for Equatiorial Positions Bulky groups e.g., t-butyl have very strong interactions in the axial position and the energy difference in the two forms is particularly pronounced (around 5 kcal/mol) so that 99.9% of tert-butylcyclohexane is maintained in the equatorial form (II),

2) Disubstituted cyclohexane In the trans form, two methyl groups are present in the equatorial position. In Cis form, 1,3 interactions are possible. Therefore the trans form will be more stable than Cis-isomer (a-e form) Ex.: In 2-Methyl cyclohexanol, the trans form is more stable than cis form. The cis form is readily converted into the trans form when heated with sodium. In 1,2 disubstituted cis compounds one substituents must be axial and other equatorial. If the substituents differ in size, 1,3-interactions will be most powerful, when the larger group is axial. Thus the conformation

with lower energy will be the one in which the larger group is equatorial. This is the preferred form. Ex: In cis-2-methylcyclohexanol, the methyl group is larger than the hydroxyl and so the preferred form will be la- hydroxy-2e- methyl. In 1,3 compound the cis (e,e) from will be more stable than cis (a,a) and will also be more stable than the trans (e,a) conformation. The most stable conformation of 1,3-dimethylcyclohexane is cis-1,3 (e,e) form. In 1,4 Compounds the two cis forms are identical when two groups are identical. The trans-(e,e) from will be more stable than cis-(a,e) form. The following generalizations may be made 1) In cyclohexane systems, mono, di, tri and poly substituted derivatives always tend to take up the chair conformation whenever possible. 2) The chair conformation with the mazimum number of equatorial substituents will be the preferred conformation. It is satisfactory when the internal forces due to dipole interactions or hydrogen bonding are absent. When these are present, it is necessary to determine which forces predominate before a conformation can be assigned to the molecule.

If the energy of the system is less than its stability is more. Number of gauche butane interaction is more its energy is more. 1,2-dibromocyclohexane The dipole moment for the diaxial isomer is assumed to be zero. The calculated moment for either the diequatiorial or the equatorial-axial isomer is 3.09 D. The observed moments for the two known isomers are 3.12 D. and 2.11 D. The higher moment corresponds to the cis isomer. The diaxial form makes an appreciable contribution to the trans isomer to account the dipole moment value.

Fused-Rings: The Decalins The compound bicyclo [4,4,0] decane, better known as decalin, exists in two diasteroisomeric forms depending on the way in which the two cyclohexane rings are fused together. It is also readily determined from the models that cis and trans decalins are diastereomers as they cannot be interconverted by bond rotations. Decalin may be considered as a fusion of a four carbon chain i.e., - CH2 CH2 CH2 CH2-shown by arrows to the chair form of cyclohexane. Trans-decalin is fused with this four-carbon chain (equivalent to largest groups) in equatorial positions while the cis-decalin this fusion involves equatorial-axial positions. As a result in cis-decalin the two hydrogens attached at the point of fusion between two rings lie on the same side of the ring while in trans-decalin, they are on opposite sides. In fact, cis-decalin exists as an equilibrium between two enantiomeric all-chair conformations which are interconvertiable as a result of conformational flipping which is typical of monocyclic cyclohexanes. As a result, any substituent attached to the cis-decalin system is more or less free to adopt the equatorial orientation. cis-Decalin is dissymmetric in both conformations which are non-super imposable mirror images of each other.

Because of rapid ring flipping between these forms the compound is a non- resolvable dl-pair. On the other hand, trans-decalin has a unique and rigid conformation, inversion of which is not possible, as it would otherwise afford a highly strained system with one ring attached to the other by two axial bonds. As a result, a substituent is constrained to remain in a particular conformation which is dependent on its configuration. The rigid conformation of trans-decalin has been used in the same manner as t-butyl groups to study the relative rates of equatorial and axial substitution. The hindered approach to axial positions has been demonstrated trans-Decalin has a centre of symmetry and is therefore, optically inactive, It may be further noted that substituents located at the point of fusion between two rings (angular positions) in cis-decalins are axial with respect to one ring while equatorial with repect to the other. However in the case of trans- decalins these are axial with respect to both the rings. It may be remembered that simple rotation of groups about carbon-carbon bonds cannot bring about inter-conversion of cis-and trans-decalins. Therefore, in this respect decalins resemble the cis-and trans, 1,2-disubstituted cyclohexanes and as has already been said, in decalins the 1, 2-substituents are two ends of four carbon chain.trans-Decalin as a result is stabler by about 2.7 kcal/mole (11.3kJ/mole) as compared with cis-form.

Exercise 1. Discuss the Principles of symmetry 2. Define (i) Enantiomer (ii) Diastereomer (iii) Chiral centre (iv) Asymmetric molecule (v) Dissymetric molecule 3. Write note on Atropisomerism of (i) Biphenyls (ii) Allenes and spiranes 4. Give an account of (i) Newman, Sawhorse and fischer notations of stereoisomers (ii) Interconversions of Newman, Sawhorse and fischer notations 5. What is geometrical isomerism? give an account of Determination of configuration of geometrical isomers, 6. Write a note on Stereospecific and stereoselective synthesis 7. Describe conformational analysis of (i) Cyclohexane (ii) Decalins 8. Explain Cahn – Ingold – Prelog rules for assigning R.S configuration with suitable example. 9. Illustrat with example E & Z nomenclature.

Unit – III

3.1 Substitution reactions are those chemical reaction of organic compounds in which an atom or a group of atoms is replaced by another atom or by a group of atoms.

From the expression it is evident that in substitution reaction a sigma () bond is replaced by a new sigma bond. This reaction is also known as displacement or replacement reaction. Nucleophilic Substitution Reaction (SN): In this type of substitution reaction the incoming group is nucleophilic in nature and as a result of its attack the leaving group is eliminated as a nucleophile. Nucleofuge or Nucleofugal group: Nucleofuges are such type of leaving groups which leave the remainder of the substrates with bonding electron pair is substitution reaction. Some of the most common nucleofuges are halogens, hydroxyl (OH) , cyanide (C N ,) amino (-NH2) i.e., any nucleophilic groups. Aliphatic Nucleophilic Substitution Reactions The general nature of nuclephilic substitution reactions at saturated organic molecule may be pictured as

From the above representation it is evident that in this substitution process a nucleofuge (leaving group) is eliminated followed by the attachment of the incoming nucleophile (Nu). Mechanism of nucleophilic substitution reaction Mechanistically, nucleophilic substitution reaction of aliphatic compounds may take place in two distinct paths, viz, (i) stepwise path and (ii) simultaneous or concerted path. Step-wise path SN1

In this path substitution occurs in two steps Step 1: In the first step the departing nucleophile (nucleofuge) leaves the centre of the reaction with bonding electron pair resulting in the formation of carbocation as the reaction intermediate.

Generation of carbocation slowly occurs as shown below:

Thus, the formation of carbocation involves a transition state. Step 2: In the second step the incoming nucleophile with its pair of electrons is rapidly attached to the carbocation formed in step I, with the formation of the product.

Attachment of nucleophile is a fast process and may proceed through the slow formation of a transition state.

Of these two, the first step i.e., rate of tlic formation of a carbocation is the slowest and so from kinetic point of view this step is the rate-determining step (R.D.S). From above path in this rate-determining step concentration of only one molecular species is undergoing change. For this reason this mechanistic path is designated as unimolecular nucleophilic substitution reaction abbreviated as SN1. This path is a first order reaction as the concentration of one molecule of substrate

is involved. This path, as seen above involves two transition states, viz., (i) one for the formation of carbocation intermediate and (ii) other for yielding the product.

The overall path of SN1 reaction may be represented by the following energy profile diagram.

Simultaneous path SN2 In this path of substitution, departure of the leaving group and attack by the incoming nucleophile proceed simultaneously without the formation of any intermediate. Orbital description of the path

Kinetics of the reaction The overall path can be represented by the energy profile diagram as shown below:

This reaction follows a second order kinetics Factors Governing SN1 And SN2 Reactions

Whether a nucleophilic substitution proceeds through SN1 or SN2 path is controlled by some factors as discussed is sequel. Structural Factor

In general nucleophilic substitution reaction follows either SN1 or SN2 path. In SN1 path, substitution proceeds through the formation of carbocation. So it is logical to assume that any structure which favours the formation of stable carbocation favours SN1 path. Let us consider some structural features of the substrate which can favour the formation of stable carbocation and hence SN1 path. (a) In the series

The order of probability of SN1 is IV > III> II> I This is because the order of stability of respective carbocations is

On contrary the probability of SN2 increases with the decrease in the stability of carbocation. (b) The presence of -bond in the adjacent position of the reaction centre may 1 stabilise the carbocation that may be produced during the reaction and SN proceeds smoothly. Thus,

It may be pointed that in some cases presence of -bond at  position may not favour substitution as in the case of benzylic compound.

In this case, resonance stabilization makes the substrate less reactive. Further, the presence of -bond at -position like vinylhalide and halogenobenzene, resonance stabilises the substrate itself and no substitution occurs. i.e.

Due to resonance halogen atoms are strongly held and can not be readily replaced. In contrast, allenic halides can stabilise carbocation through resonance and so undergo normal SN1.

(iii) Steric effect: Steric effect can profoundly influence the course of nucleophilic substitution. (i) Neopentyl halide is very unreactive towards nucleophilic substitution. Its structure suggests that its path of nucleophilic substitution (say hydrolysis) is expected to be SN2 as the formation of less stable, carbocation (1) does not favour SN1. The transition state for SN2 is a pentaco-ordinated compound like

It is evident from the above representation that bulky substituents at carbon may create steric hindrance and in fact it has been found that the larger the size of subsistent greater becomes the strain at central carbon atom due to overcrowding and so SN2 (backside attack) does not operate. This is the situation with neopentyl halide.

Bulkier group attached to the reaction centre creates sufficient steric hindrance and backside attack by the incoming nucleophile is not favoured. Low Reactivity of Vinyl and Aryl Halides Halogen attached to a doubly bonded carbon or on aromatic nucleus is usually quite unreactive. The aryl halides show extremely low reactivity towards nucleophilic substitution reactions. They usually do not undergo nucleophilic substitution reactions unless electron-withdrawing groups are located ortho or para to the halogen on the aromatic ring. Similarly, vinyl halides are very much unreactive toward nucleophilic substitution reactions than their saturated counterparts. The low reactivity of alkyl and vinyl halides is because of that they contain shorter and stronger carbon-halogen bond. For example, in chlorobenzene and vinyl chloride the C-CI bond length is 1.69A, as compared with a bond length of 1.77-1.80 A in a large number of alkyl chlorides. This is attributed to the SP2 hybridization of the carbon atom holding halogen. Since, carbon atom having SP2 hybridization is more electronegative than sp3 hybridized carbon atom, therefore, the carbocation intermediates formed by the ionization of aryl and vinyl halides are thermodynamically less stable than alkyl carbocations. This prevents the SN1 mechanism from operating in aryl and vinyl halides. The other reason for this unreactivity is that the -orbital of the double bond overlaps with the p-orbitals of the halogen atom to form delocalized cloud of the -electrons with the result that C-X bond attains a partial double bond character. The partial double bond character of the C-X bond results in strengthening of the bond and hence it is difficult to break as compared to single bond. Both of these effects inhibit nuclophilic substitution reactions of either the SN1 or SN2 type, thus net reactivity of the molecule is considerably less than that of saturated alkyl halides.

High Reactivity of Allyl and Benzyl Halides On the other hand, allyl halides and benzyl halides are more reactive than saturated halides. Allyl and benzyl halides are especially reactive under SN1 conditions because of the resonance stabilization of the intermediate allyl and benzyl carbocations, respectively. The resonance stabilization of intermediate carbocations has an acceleration effect on the ionization of allyl and benzyl halides. For example, solvolysis of allyl iodide in water proceeds much faster than the solvolysis of propyl iodide. Allyl and benzyl halides not only react faster than simple halides in SN1 reaction, but they react much faster than simple halides in SN2 reaction as well. Allyl bromide, for example, is about 100 times more reactive towards simple SN2 reactions than is propyl bromide. The double bond stabilizes the SN2 transition state by conjugation with p orbital at the carbon atom under attack. Any stabilization of the transition state will, of course, accelerate the reaction by lowering the energy barrier.

Change of Mechanistic Path Due to Structural Effect (SET Mechanism) When triphenyl methyl halide is treated with potassium tert-butoxide, the expected substitution product is obtained during the attachment of attacking

nucleophile-tert-butoxide anion, path is changed from ionic to radical by the transfer of a single electron from tert-butoxide anion to triphenyl methyl carbocation with the generation of radicals of two species which ultimately collapse into product as shown below.

Supportive evidence for the formation of free radicals during the course of the nucleophilic substitution has been secured from ESR study. Role of Solvent (Solvent factor) In nucleophilic substitution reaction solvent used has immense role. In this reaction whether it proceeds through SN1 or SN2 path a carbon-leaving group bond must be broken, obviously, question arises where from the necessary energy for bond breaking comes? In SN2 reaction along with the cleavage of bond simultaneously there is formation of a new bond. It is known that the formation of bond is always associated with the release of energy. So it may be concluded that is SN2 necessary energy required for bond cleavage may be obtained from that released during bond formation. But in SN1 the scenario is different. There is no such simultaneous bond formation during the breakage of the bond. It has been observed that when a SN1 reaction is carried out in gas phase (i.e., in absence of any solvent) energy required for bond breaking is 150Kcal/mole. But if the same reaction is carried out in presence of a solvent under identical condition the energy required for bond breaking is only 20Kcal/mole. Therefore, it follows that the source of major share 1 of energy required for bond breaking in SN is solvent. Again, question arises in what way the solvent supplies the energy? It has been assumed that as the bond formation always occurs with the release of energy, solvent molecule most probably forms some sort of weak bond with the substrate molecule. Polar solvents particularly protic solvent can readily form H-bond with another atom which can donate electrons. In SN1, the leaving group is eliminated as a

nucleophile which means leaving group can act as electron donor. Thus, the course of SN1 reaction in polar protic solvent may be pictured as,

As a result of the H-bond formation, carbon-leaving group (C-X) bond is stretched and so the formation of carbocation which is essential for SN1 reaction is favoured. On the other hand, the leaving group (X) which is eliminated as nucleophile is stabilised through H-bond formation and the probability of reverse reaction is minimized to a large extent. Thus, the rate of SN1 reaction is increased if polar protic solvent is used in place of aprotic solvent. As SN2 path is a path of non-ionisation, it appears at first sight that the polarity of the solvent may not have any role in SN2. But it has been observed that the rate of SN2 is decreased if polar solvent is used instead of non-polar solvent or the reaction is conducted in the absence of any solvent. This phenomenon may be explained by considering that polar protic solvent forms H-bond with the attacking nucleophile and stabilises it. As a result nucleophile becomes less active as attacking reagent and so over all rate of SN2 decreases. Nature of the Leaving Group Less the basicity of leaving group more becomes its tendency to leave reaction and hence more is the probability of nucleophilic substitution reaction. The order of activity of members of halogen series as leaving group is − IBrClF because the order of their basicity is FClBrI. Nature of Attacking Nucleophilie Nucleophilicity of a reagent depends upon the easy availability of electrons in it as well as its capability of donating the same to an electron acceptor i.e., to an electrophile the reason for the order of nucleophilicity of the halogens as I Br  CI  F because their order of atomic size is I Br  CI  F. Stereochemical Implications of Nucleophilic Substitution Reactions Both SN1 and SN2 reactions have interesting stereochemical implications which may be summarised as depicted below.

Stereochemistry of SN1 Reaction It has been suggested that SN1 substitution reaction proceeds through the formation of carbocation in the rate determining step. The carbocation has planner configuration in which central carbon atom is in Sp2-hybridised state and the three groups are bonded to it through three sp2-hybrid orbitals. All the three bonds are in the same plane making an angle of 120 to each other. The remaining bond is a vacant p-orbital which is perpendicular to the plane of three bonds as shown in figure below.

When the HOMO of the attacking nucleophile approaches this carbocation interaction may involve either of two lobes of vacant p-orbital (acts as LUMO) with equal probability as a result of which incoming group may be attached to the central carbon in either directions forming two stereoisomers in equal amounts. Now if the central carbon atom of the substrate is an asymmetric one then these two stereoisomers are two opposite optical isomers or in other words in such situation the product is a mixture of two opposite optical isomers in equal amount i.e., a recemic mixture. Thus, it may be concluded that SN1 substitution reaction at chiral centre should proceed with the formation of racemic product.

Stereochemistry of SN2 Reaction In SN2 reaction the attacking nucleophile approaches the central carbon atom from the opposite side of the leaving group. It is therefore, highly expected 2 that SN -reaction occurring at chiral centre should always yield inverted product i.e.,

Thus, SN2 reaction is both sterospecific and stereoselective in nature. SN1 Reaction (retention in configuration) Substitution Nucleophilic Intramolecular Under normal condition nucleophilic substitution proceeds either through

SN1 or SN2 path. But retention in configuration in the product of chiral substrate does not occur in either of two paths. However, under certain circumstances configuration of the substrate is retained in the product. Most widely studied example is the replacement of alcoholic hydroxyl at chiral carbon by chlorine through the reaction with thionyl chloride. Thus,

The retention in configuration in this particular reaction has been explained on the basis of formation of an intermediate-chlorosulphite.

The intermediate chlorosulphite forms a cyclic transition state which then collapse into the product as indicated below:

From above path of the reaction it is evident that during the substitution the attacking nucleophile (CI) approaches the chiral carbon centre internally from the same direction in which the C-O bond (carbon-leaving group bond) is connected and so the configuration of the substrate remains unchanged in the

100

product. Since the attacking nucleophile attacks the reaction centre internally it is i known as internal nucleophilic substitution reaction usually expressesd as SN . Neighbouring Group Participitation Neighbouring group situated at appropriate position from the reaction centre has tremendous effects in controlling the course of reaction. Neighbouring substituents having readily available electron centre or an atom with lone pair of electrons generally participate during the course of the reaction. It has been observed that such substituents when situated at  or  position with respect to the reaction centre, the effect becomes maximum. Normally the neighbouring group approaches the central carbon atom from the opposits direction of the departing group yielding a cyclic intermediate with the expulsion of the departing group the nucleophilic substitution involving neighbouring group participation proceeds with retention of the configuration of the substrate in the product. The above path of the reaction may be expressed as. Step 1:

Step 2:

It has been observed that formation of the cyclic intermediate is the rate determination step and this step is an intramolecular reaction, its energy and activation is low and hence the rate is largely increases then the similar reaction where there is no participation of neighbouring group. This unexpected increase in

101

the rate of the reaction due to the participation of the neighbouring gorup is known as anchimeric assistance. Most commonly illustrated example of participation of neighbouring group in nucleophilic substitution is the hydrolysis of -halohydrin in dilute alkali

Similar retention in configuration is observed in the hydrolysis of - haloacids in dilute alkali

Another commonly used example that may be cited is the hydrolysis of - chlorosuphide in aqueous dioxan.

Presence of -bond in the proper position can also offer anchimeric assistance. Thus, anti-norbornenyl tosylate undergoes acetolysis very faster than expected.

102

It has also been observed that phenyl group situated at favourable position can be an effective neighbouring group participant. Thus, -(p-hydroxylphenyl)- ethyl chloride when treated with alkoxide yields ether at a very faster rate than expected.

Alkoxide ion may attack either  or  carbon and both isomers may be formed. 3.2 Aliphatic Electrophilic Substitution For aliphatic electrophilic substitution, we can distinguish at least four possible major mechanisms, which we call SE1, SE2 (front), SE2 (back), and SEi. The SE1 is unimolecular; the other three are bimolecular. Bimolecular Mechanisms. SE2 and SEi The bimolecular mechanisms for electrophilic aliphatic substitution are analogous to the SN2 mechanism When the attacking species is an electrophile, which brings to the substrate only a vacant orbital.

Both the SE2 (front) and SE2 (back) mechanisms are designated DE AE in the IUPAC system. With substrates in which we can distinguish the possiblity, the former mechanism should result in retention of configuration and the latter in inversion. A portion of the electrophile may assist in the removal of the leaving group, forming a bond with it at the same time that the new C-Y bond is formed.

103

This mechanism, which we call the SEi mechanism. The SE1 Mechanism The SE1 mechanism is analogous to the SN1. It involves two steps-a slow ionization and a fast combination. Step 1

Step 2 The IUPAC designation is DE + AE. S1 reactions do not proceed at bridgehead carbons in bicyclic systems (p.300) because planar carbocations cannot form at those carbons. If a carbanion is planer, recemization should occur. If it is pyramdal and can hold its structure, the result should be retention of configuration. What is found is almost always recemization. Aliphatic Diazonium Coupling

If a C-H bond is acidic enough, it couples with diazonium salts in the presence of a base, most often aqueous sodium, acetate. The reaction is commonly carried out on compounds of the form Z-CH2-Z, where Z and Z are as defined on p.464, e.g., -keto esters, -keto amides, malonic ester. The mechanism is probably of the simple SE1 type.

104

Aliphatic azo compounds in which the carbon containing the azo group is attached to a hydrogen are unstable and tautomerize to the isomeric hydrazones, which are therefore the products of the reaction. When the reaction is carried out on a compound of the form z-CH-z, so that the azo compound does not have a tautomerizable hydrogen, if at least one z is acyl or carboxyl, this group usually cleaves.

So the product in this case too is the hydrazone, and not the azo compound. In fact, compounds of the type 16 are seldom isolable from the reaction, though this has been accomplished. The cleavage step shown is an example of and, when a carboxyl group cleaves, of 2-40. The overall process in this case is called the Japp-Klingemann reaction and involves conversion of a ketone or a carboxylic acid to a hydrazone. When an acyl and a carbocyl group are both present, the leaving group order has been reported to be -MeCO > -COOH > PhCO-. When there is no acyl or carboxyl group present, the aliphatic azo compound is stable.

3.3 Aromatic Nucleophilic Substitution Reactions Nucleophilic substitution reaction are not very common in aromatic compounds. This is because of the fact that (i) nucleophilic substitution proceeds by the attack of the incoming nucleophile followed by the elimination of a departing nucleophile. Aromatic compounds are highly electron rich species due to the presence of a closed circuit of  electrons above and below the plane of the molecule, attack by nucleophile is not favoured due to electrostatic repulsions and (ii) leaving groups particularly electron releasing groups are tightly bound to the aromatic ring due to their participation in resonance with aromatic ring as shown below.

105

Due to this resonance, it is very difficult to replace such group form the aromatic ring by any incoming nucleophile. However, under certain conditions as well as with suitably substituted aromatic compounds nucleophilic substitution reaction can occur. As in aliphatic compounds nucleophilic substitution reactions in aromatic compounds may be of two types-SN1 and SN2. SN1-mechanism SN1-reactions are less common in aromatic compounds because the formation of carbocation which is essential for this type of mechanism is not favoured in aromatic compounds due to the lack of its (phenyl cation) stabilization by conjugation. This type of mechanism in aromatic compounds is only possible in the thermal decomposition of diazonium salts in aqueous non-basic solvents. During the decomposition of these salts there is formation of highly reactive phenyl cation in the rate determining step which in the second step combines with the attacking nucleophile. Thus,

where Y is incoming nucleophile. As revealed by this mechanistic path, rate of decomposition decreases when electron releasing groups are present at ortho and para positions because of their participation in resonance with the diazonium cations. The SNAR mechanism It is a bimolecular mechanistic path of nucleophilic substitution in aromatic compounds and is more general one. In this substitution, cleavage of an

106

old sigma bond and formation of a new sigma bond takes place by two-step mechanism an addition-elimination path. In the first step ipso addition (i.e., addition at the same carbon atom at which leaving group is attached) by the incoming nucleophile occurs. This is the slowest and the rate determining step. As a result of addition of incoming nucleophile a highly delocalised anion is formed which is considered to be an intermediate. In the second step, the leaving group is eliminated with the regeneration of aromatic ring. Step I: IPSO addition by the incoming nucleophile (Y)

Step II: Elimination of leaving group with the regeneration of aromatic ring

The mechanistic path which is usually denoted as SNAr (SN2) is only smoothly operates when electron withdrawing group(s) is present at ortho and para positions with respect to the leaving group. That is why chlorine in chlorobenzene is not readily replaced but chlorine in ortho-nitro or parn-nitro chlorobezene is readily replaced.

107

Aromatic Nucleophilic Substitution Reaction Through Benzyne Intermediate Nucleophilic substitution reaction in aromatic compounds is also observed either under drastic condition or by the use of strong base at a very low temperature. These reactions can not be explained by SN1 or SNAR mechanistic path. An interesting observation in these substitution reactions is that often along with the normal substitution (Ipso) product, ortho product is also obtained in equal amount. Another important observation noted is that aromatic compounds having substitution reaction under similar conditions. Thus,

Based on these observations, this type of substitution reactions in aromatic compounds has been interpreted by assuming the formation of a highly strained and reactive benzyne intermediate as depicted below.

108

Step 1:

Step 2:

Benzyne is symmetrical and attack by NH 2 can take place at either of the two positions resulting in the formation of normal and cine products. Step 3:

It may be mentioned that the product obtained at position other than that occupied by the leaving group in aromatic nucleophilic substitution is known as cine product. As the above mechanism involves elimination and addition paths it is also known as elimination-addition process.

109

 NH2 removes a proton from the ortho position to chlorine. This results in the

 simultaneous expulsion of Cl and formation of benzyne intermediate. Benzyne is exceedingly reactive and reacts with any nucleophile present, in this case the solvent liquid ammonia, to form an addition product.

The reaction is, therefore, an elimination-addition process. This is observed in chlorobenzene with labelled carbon ( 14 C) bearing the chlorine.

Thus, p-chlorotoluene on treatment with strong NaOH at 340C gives a mixture of o- and p-cresols. This cine-subsititution (aromatic nucleophilic substitution at a different position from the leaving group) supports the formation of benzyne intermediate. Further support of the mechanism comes from the observation that no reaction takes place when both the ortho positions are substituted. 3.4 Electrophilic (aromatic) substitution We know that benzene is a resonance hybrid which is a flat ring with a cyclic cloud of negative charge, above and below the plane of the ring.

110

Benzene ring therefore discourages nucleophilic attack and encourages electrophilic attack. Alkenes also encourage electrophilic attack resulting in addition while the electrophilic attack on benzene results in substitution since addition would involve loss of resonance stabilization of benzene.

Hence, the typical reactions of benzene and its derivations are electrophilic substitution. Aromatic electrophilic substitution includes a wide variety of reactions, e.g., nitration, sulphonation, halogenation, Friedel-Crafts reactions, etc. the reaction permits the indirect introduction of groups to the ring and their subsequent transformation to various other products.

H24 SO ArHHNOArNOH+→+ 322 O

AlCl3 ArHClArClHCl+→+2

SO3 ArHH+→+ SOArSO2432 HH O

AlCl3 ArHRClArRHCl+→+ Mechanism The various aromatic electrophilic substitutions follow the same mechanistic pattern which is generalised below. The reagent and the catalyst (Lewis acids or proton acids) undergo acid-base reaction to produce the attacking electrophile which then attacks the ring to form a carbocation ( complex) in the first slow step. In the second step the proton from the site of attack is rapidly removed by the base to complete the reaction. General mechanism of electrophilic substitutions

111

The energy gained in passing from the  complex to the product (regain of aromaticity) provides the energy for breaking the strong C – H bond. It may seem that the formation of  complex would involve high energy. This is, however, not so because the energy liberated by the formation of a C – E bond and the delocalization of the positive charge lowers the energy of the  complex. The rate of reaction does not involve the breaking of C – H bond. This has been established by isotope effect. The rates of reactions are the same on replacement of hydrogen by deuterium or tritium. Hence, the rate for the substitution reaction is determined by the slow attachment of the electrophile to the ring in the first step. Let us now consider some of the individual substitution reactions. (a) Nitration Nitration of benzene is effected with a mixture of concentrated nitric and sulphuric acids. In the absence of sulphuric acid the reaction is slow. It is suggested that H2SO4 acts as a strong acid and protonates HNO3 to generate  nitronium ion, NO2 . This has been confirmed by various methods.

 H24 SO HO−+−+++ NOH2242232 SOH O NOHSOH O NO2HSO44 

Overall reaction is HNO2H32423+++ SON O2HSOH O 4 . The nitronium ion then attacks the benzene ring to form a carbocation in the first step.

In the second step., a fast abstraction of hydrogen from the sit of attack by the  base HSO4 completes the reaction. 

112

The presence of appreciable amount of water in the acid mixtrue is not desirable since it reduces the nitronium ion; hence, the use of concentrated acid mixture.

HSO4 NOHOHNOHSOHNO222243++3 Phenol, which is highly reactive due to the mesomeric effect of the OH group, is nitrated even with dilute HNO3. A small amount of phenol is oxidized to produce  HNO2 which with HNO3 gives nitrosonium ion, NO. The latter nitrosates the reactive phenol to yield nitrosophenol which si rapidly oxidized to nitrophenol with HNO3 and nitrous acid is produced by reduction of HNO3. With the progress of the reaction more and more nitrous acid is produced and the reaction rate is increased.

(b) Sulphonation Benzene on heating with concentrated or better with fuming sulphuric acid gives benzene sulphonic acid, C6H5SO3H. Sulphonation can also be effected with ClSO3H.

C66246532 HH++ SOC H SO HH O

The reaction is slow with concentrated H2SO4 but rapid with oleum or SO3 in inert solvent. The electrophile is SO3 which is present in small amount in H2SO4. 

2H2 SO 4 SO 3++ HSO4 H 3 O

The electrophile, SO3, is neutral but has a powerful electrophilic sulphur which attacks the ring.

113

The rate-determining step involves the breaking of C-H bond since deuterated benzene is sulphonated more slowly (isotopic effect). The reaction is reversible.

On treatment with steam SO3H group is replaced by hydrogen. The reversibility of the reaction has practical utility. (c) Halogenation Free halogens can attack activated benzene rings but Lewis acid catalyst is required for benzene ring. It is suggested that probably benzene first forms a  complex with the halogen molecule, e.g., Br2. The Lewis acid (FeBr3) then polarizes the Br – Br bond and helps in the formation of a  complex between benzene carbon and the electrophilic end of the polarized bromine by removing the incipient bromide ion. Subsequent abstraction of hydrogen in the second step completes the reaction.

The order of reactivity of the halogens is F2>Cl2>Br2>l2. Fluorine is too reactive for practical use. Under ordinary condition, iodination fails. In the presence of  HNO3 direct iodination has been effected. The attacking electrophile I is produced by HNO3. (d) Friedel-Crafts reaction Alkylation and acylation of aromatic rings with alkyl halides and acid chlorides or anhydrides respectively in the presence of Lewis acids, eg., AlCl3, FeBr3, BF3, BCl3, etc., is known as Friedel-Crafts reaction.

114

(i) Alkylation-The function of the catalyst is to porovide a real or potential carbocation for the electrophilic attack. When the alkyl group can form a stable carbocation as in case of 3 halide the attacking species is the real carbocation which forms an ion pair (23).

In other cases, a polarized complex with a potential carbocation is the attacking species.

The intermediates (23) and (24) have been isolated in some cases. It has been observed that the same alkylhalide gives a rearranged and an unrearranged product with different Lewis acid catalysts.

AlCl 3 C HMe+→ C.CH ClC H CMe CH Me 66326522 Rearranged

FeCl3 C HMe+→ C.CH ClC H CH CMe 66326523 Unrearranged

Since AlCl3 is a stronger Lewis acid than FeCl3, it is presumed that the complex with AlCl3 is so strongly polarized than the alkyl group attains almost a free carbocation character to undergo rearrangement.. −−++

Me323223 C−→ CH ...... Cl...... A l Cl Me C.CH Me...... Cl....A l Cl The alkylating reagent besides alkyl halides may be aliphatic alcohols, alkenes, ethers, etc., in the presence of strong proton acids which generate the coarbocation for the electrophilic attack.

115

(ii) Acylation-Acylating reagents are acid chlorides or acid anhydrides in the presence of Lewis acid. The electrophilic species may be (a) acyl cation as an ion pair or (b) a polarized 1  1 complex. Probably both mechanisms operate depending on conditions.

In both cases, one mole of the catalyst remains complexed with the product, ketone. Hence, slightly more than one mole of Lewis acid is required for acylation. Acylation may be effected with acid anhydrides also. The attacking  species in this case may be a free R CO or RCOCI. Effect of substituents in aromatic rings In planning syntheses based on substitution of monosubstituted benzenes, it is necessary to have prior knowledge to predict which position of the ring is most likely to be substituted and how readily the substitution will occur. It has been observed that the group already present influences the orientation of substituion of the incoming group and the reactivity of the ring. Mono-substituted benzene on further substitution gives either m-isomer predominantly or a mixture of o- and p-isomers predominantly. Groups (substituents) which induce faster electrophilic attack than on benzene are called activating and in the reverse case (i.e., if slower) they are called deactivating. On the basis of the above, groups have been divided into two classes, ‘A’ and ‘B’.

Thus, activating groups are o-/ p orienting with activation, e.g., -NR2, -NH2, - OH, -OR, -NHCOR, -OCOR, etc. Deactivating group are m-orienting with deactivation, e.g.,  -NO2, -CHO, -CO2H, -SO3H, -CN, - NR3 , -CN, -CCl3 etc.

116

Let us now consider the electrophilic substituion in C6H5OR which has one activating group. Benzene derivatives containing activating group have in common an atom, adjacent to the ring, that has at least one electron pair. The electronic displacement by +M(mesomeric) effect of these groups increases the overall electron density of the ring. The electron density is more marked at o-and p-positions than at m-position.

Hence, these groups cause facile (fast reaction) electrophilic substitution at o- and p-positions. This effect of the group -OR on the rates of attack at o-, p- and m-positions can be explained on the basis of the stabilities of the transition states formed on attack at these positions. This, however, is usually not possible and hence the stabilities of the  complexes which closely resemble the transition states in energy and structure will be examined. Thus,

117

It is seen that the  complexes formed on attack at o- and p- positions are both stabilized by for canonical structrues relative to three for m-attack. The extra fourth structures (marked X1 and X2) are specially stable because all the atoms have complete octet. This factor overshadows the electron-withdrawing inductive effect of the electronegative oxygen atom. Thus, the unshared pair of electrons on oxygen atom helps in greater delocalization of the positive charge formed on attack at o- and p-positions. This gives added resonance stability to the respective carbocations. As the more stable carbocations are expected to be formed more rapidly, the substituion products are nearly completely o-/p-isomers. Substitution in chlorobenzene Chlorine is strongly electronegative. Its electron- withdrawing inductive effect deactivates the ring at all positions, yet chlorine aids o- and p-substitutions. On drawing all the possible canonical forms of the  complexes formed on attack at o-, p- and m- positions as for C6H5OR earlier, it will be seen that the extra foruth canonical forms (a) and (b) (cf X1 and X2 for C6H5OR) for the o- and p- complexes are specially stable since all the atoms in each have complete octet and the delocalization of the positive charge is beyond the ring.

Hence, these canonical forms make great contributions to the respective hybrids and strongly stabilize them relative to the  complex for the meta-attack.

Therefore, though C6H5Cl is less reactive than benzene, it undergoes. o-/p- substitution. Substitution in C6H5Cl is, however, more difficult than in benzene due to overall deactivation. (To draw the resonance forms of all the  complexes for C6H5Cl, substitute -Cl for -OR in the canonical forms given for C5H5OR.)

118

Substitution in toluene Although there is no unshared pair in CH3 group, toluene undergoes o-/p-substitution. This is due to the +1 effect in addition to hyperconjugative effect of the methyl group. As before let us examine all the resonance forms of the  complexes. It is seen that one of the resonance forms in each case of attack at o- and p-positions has a positive charge on a carbon adjacent to the CH3 group.

These forms are specially stable being 3 carbocations. Such form is absent in case of attack at m-position. This outweighs the stability of the  complexes formed on attack at m-position. Hence toluene undergoes o-/p-substitution. In case of phenyl group substituted in benzene, an electron pair of the substituent (phenyl) group may stablilize the canonical forms of the  complexes for o-and p- attacks.

Hence, biphenyl undergoes faster electrophilic attack than benzene at o- and p- positions. It should be rememebered that the effect of either activating or deactivating groups is reflected at ortho and para positions. Thus,

119

Substitution in benzene with deactivating substituents substituents Deactivating are strongly electron-withdrawing due to a positively charge or positively polaized atom adjacent to the ring.

Hence, these groups overall deactivate the ring by electron withdrawal. The deactivation is more marked at o- and p-positions than at m-position. This can be seen from the stabilities of the  complexes formed on attack at these positions, e.g., in C6H5NO2.

120

The canonical forms (Y1) and (Y2) on attack at o- and p-positions have each positive charges on adjacent carbon. These forms are of high energy and do not contribute to the hybrid. Consequently, the delocalization of the positive charge restricted in two canonical forms of the ring for o-/p-attack is less than for m- attack which no such destabilizing forms are present. Thus, the -NO2 group does not aid the attack at any position specially discourages the attack at o- and p- positions.

The attack at any position in C6H5NO2 is therefore slower than in benzene and it is specially slow o-/p- positions. Hence, C6H5NO2 undergoes m-substitution predominantly. From the above it is seen that the effect of either activating or deactivating groups is reflected at ortho and para positions while m-position remains practically unaffected. Hammett Equation Hammett studied the kinetics of larger number of organic reactions involving the aromatic ring. He found that the rates of any given chemical reaction within the series could be correlated using a simple equation, which latter on came to be known as the Hammett Equation. Let us have a close look at a simple ionization reaction – the ionization of substituted benzoic acids. When benzoic acid (X = H) is dissolved in water, it would undergo ionization as shown in wherein K is the equilibrium constant for this reaction. When the substituent X is a group other than hydrogen, the electronic effects of the substituent become operative and there would be a change in the value of K. Hammett assumed that for substituents at the p- and m-positions, contributions due to steric effects would

121

be unimportant in this ionization reaction. These rate constants could be correlated by means of a simple equation called the HAMMETT EQUATION. In this equation, the value Kx is the equilibrium constant for the Log (Kx/K0) = x reaction when the substituent is ‘X’ (a substituent other than ‘H’), K0 is the equilibrium constant for the reaction when the substituent is ‘H’, x (sigma x) is a substituent constant, which reflects the polar effects of the substituent X on the reaction and  (rho) is the reaction constant, which is independent of X but depends only on the reaction being studied and the reaction conditions such as solvent and temperature. Hammett chose this reaction as the reference reaction (because the values of the ionization constants were accurately known) and assigned unity (one) as the value of  for this reaction. Thus, for benzoic acids, the above equation could be rewritten as follows. Using this procedure Hammett obtained a Log(Kx/K0) = x series of x values for different X substituents, Once accurate value for x were known, these values were substituted in the Hammett Equation for several other reactions to obtain  value for those reactions.

For example, one could study the rate of alkaline hydrolysis of substituted ethyl benzoates. From the Hammett Equation one can get a numerical value for , which would be the reaction constant for that reaction at that temperature and in that particular solvent. In the same way, one could obtain the  values for other alkyl benzoates. Such studies enable chemists to quantitatively evaluate the effects of the leaving group-OR in these hydrolysis reactions. The same procedure was extended to several other reactions. In this way, a series of reaction constants ( values) were obtained from the Hammett Equation.

122

Hammett Plot

One could also obtain the  value through a graphical method. Hammett observed that a plot of log (Kx/K0) against x gave a straight line graph for several reactions. Such plots are now known as the Hammett plots. The  values for a given reaction could be obtained from the slope of such plots. In these discussion, the substituent constants () are considered to be independent of the nature of the reaction and the reaction conditions. They reflect only on the electronic (polar) effects of the substituents on any reaction. In the same way the reaction constants () are independent of the substituent effects and reflect only on the nature of the reactions. In other words, the  value reflects on the nature of the transition state of the reaction, which is influenced by the reaction conditions. Therefore, the  value is a quantitative measure of the polar nature of the transition state. In complex reaction mechanisms, such studies on reaction kinetics measure the rate of the slowest step. It could therefore be concluded that the  value gives a quantitative picture the polar nature of the slowest step in a given reaction mechanism. Some notable exceptions were also observes. In fact, Hammett ignored all those compounds, which did not fit into his linear plot. Attempts to understand these features have led to the development of a very useful technique for understanding of the polar nature of the transition states.

123

Through Conjugation Hammett observed that the p-substituents, which could conjugate with the site of the reaction and o-substituents, which could have significant steric influence, do not provide the expected straight-line graphs. In his studies, he set them aside. Later on, other workers studied these deviations. Hammett assumed that the effect of a substituent is same on both sides of the chemical equation. Let us have a close look at the ionization of p-nitroanilinium hydrochloide. Ionization of this acid gives p-nitroaniline and a proton. In p-nitroaniline, the lone pair of electrons on the amino-nitrogen could conjugate with the nitro group and provide additional canonical structures. On the other hand, such a conjugation is not available for the salt. Therefore, in such cases, the substituent effects are no longer same on both sides of the equation. In such reactions, the electron withdrawing substituents at the p-position showed deviations from the expected straight line graph. A correction was applied for such deviations to bring them back to the normal Hammett plot. The new sets of value thus obtained were called - values. This new constant holds good for those reactions that have increased electron density at the reaction site. Reactions that involve the development of anions as the rate-determining step of the reaction give linear plots with -.

124

Similarly, reactions that proceeded through electron deficient TSs also gave nonlinear Hammett plots. Solvolysis of substituted benzyl halides showed marked deviations from the normal Hammett plot for electron donating substituents. Corrections applied to these carbonium ion reactions gave + values, Thus, Hammett correlation with - values suggests that an electron rich transition state is occurring during the rate-determining step of the reaction. On the other hand, Hammett correlation with + values suggests that an electron deficient transition state is occurring during the rate-determining step of the reaction.

Significance of the Hammett Constants The Hammett constants ‘’ have different values for meta and para substituents indicating that the polar influences are not same at these positions. A

125

few values are presented below. Students are referred to the advanced texts for more detailed tables and comments. The following points are to be noted.

❖ + values denotes electron withdrawing nature of X, with - values denotes electron donation. ❖ Polar effects are more pronounces at the p-position than at the m-position (except for the halogens). ❖ Groups having + are m-directing and deactivating, while groups having -  are o/p directing and activating (except for the halogens).

❖ When the m and p values opposite signs, this indicated that the inductive and mesomeric effects are acting in opposite directions. This is seen well

in the case of –OH, -OCH3 and –OPh groups. In the case of –NO2 group, the lone pair on nitrogen is no longer available for mesomeric electron donation. Consequently the inductive and mesomeric contributions are electron withdrawing. ❖ In the case of halogens, the + values indicate that group is electron withdrawing and therefore deactivating, which is indeed the case.

However, p has a larger negative value than m. This suggests an overall

126

electron donating mesomeric effect at the para position and therefore the o-p directing effect.

❖ In the case of NH2 group, m is negative. One would have expected a positive value here. This reversal has been attributed to the strong basicity of the lone pair on nitrogen. The meta-amino group would increase the electron density at the ortho-position and thus make the o-carbon inductively electron donating. This effect is more pronounced in the case

of the phenolate ion. ❖ A nonlinear correlation with  and linear correlation with + or - indicate that there is ‘through conjugation’ operative in these molecules, at the transition state of the reaction under investigation. A correlation with + indicates electron deficient transition state and a correlation with -

indicates electron rich transition state. The sign of the  values indicate the nature of influence the substituent has on the rate determining TS. A positive sign indicates that the reaction is accelerated by electron withdrawing groups, while a negative sign indicates that the reaction is accelerated by electron donating groups. The numerical value indicated the extent to which the reaction is accelerated by electron donating groups. The numerical value indicated the extent to which the reaction could be influenced. Coupled with the information on the , + or - correlation, the nature of the TS could be assessed. These points are discussed below. The  values could also serve as a measure of the transmitting ability of ‘insulating’ carbon chains to polar effects. The following data demonstrates the point.

X-C6H4-COOH  = 1.00

X-C6H4-CH2-COOH  = 0.45

X-C6H6-CH2-CH2-COOH  = 0.21

X-C6H4-CH=CH-COOH  = 0.45 The above data suggest that a methylene group cuts the transmission of the polar effects of the X-Ar-group by 50%. Addition of one more methylene group to the chain cuts the transmission by 75%. A-CH2 group and a –CH = CH – group have identical effects effects on transmission. Linear Free Energy Relationship The Hammett Equation is a linear free energy relationship. The rate constant of a given reaction could be related to the free energy difference as shown below.

Gx = -RT In Kx

127

G0 = -RT In K0 (for unsubstituted (i.e., x = H))

log Kx – log K0 = x −G G x += 0 2.3RT2.3RT x

-G = x 2.3 RT -G0

Since, for a given reaction x, R. T and G0 are constant,  is linear with Gx Taft Equation Ester Hydrolysis is known to proceed through a tetrahedral TS. The acid and base catalysed reactions are expected to proceed through the following TSs.

Taft made two important assumptions. He suggested that the steric effects for the acid and base catalysed reactions are identical (this ignores the solvation spheres that are bound to be different for the differently polarized species). He also assumed that the resonance effects are identical at the two TSs. If these two assumptions are accepted, than any difference that could be observed has to come from the polar effects of the substituents only. Thus, Taft gave the following equation, now called the Taft Equation.

log(k/k0)B – log(k/k0)A = ** where k and k0 are the rate constant for the substituted and unsubstituted acetic acid (RCOOR’) and * is the substituent constant relating to the polar effects of R

= (CH2-X), relative to CH3. Taft gave a value * = 2.48 for this reaction. Later it was observed that these values could be related to the I values of 4-substituted [2,2,2] octanecarboxylic acids using the following realationship.

I (X) = 0.45 *(CH2X)

128

Steric Constants During his studies on the ester hydrolysis of m- and p- substituted benzoates, Taft noted that the substituent effects on the acid catalysed hydrolysis were very small. He therefore assumed that the polar effects are negligible in acid catalysed hydrolysis reactions for esters. It this were so for aliphatic esters as well, than any difference observed here has to arise form steric factors alone. Thus, he proposed the following equation for a steric constant Es. log(k/k0)A = E5

A large number of reactions fitted well into the realtionship log (k/k0) = * * suggesting that steric effects are minimal in these reactions. Wherever there was deviation, another realationship, encompassing the steric parameter was useful.

log(k/k0) = ** + Es In this equation  refers to the susceptibility of the reaction to steric effects.

129

Exercise 1. Explain the following mechanism of aliphatic electrophilic substitution (i) SE2 (ii) SEi (iii) SE1 2. Explain the following mechanism of aromatic nucleophilic substitution (i) SN1 (ii) SNAr (iii) Benzyne mechanism 3. Give an account of (i) Hammett equation and effect of structure on reaction mechanisms (ii) Hammett parameters  and , modified forms of Hammett equation (iii) Taft equation 4. Write note on general mechanism of aromatic electrophilic substitution of (i) Nitration (ii) Sulphonation (iii) Friedel – Crafts alkylation (iv) Friedel – Crafts acylation 5. What is meant by activating and deactivating groups in electrophilic substitution? Illustrate with examples. 6. Write note on (i) Neighbouring group participation in aliphatic nucleophilic substitution (ii) Substitutions at allylic and vinylic carbons. (iii) Solvent effects in aliphatic nucleophilc substitution (iv) Stereochemical factors in aliphatic nucleophilc substitution

130

Unit – IV 4.1 Addition Reactions A reaction in which the substrate and the reagent add up to form a product is called addition reaction. The reaction occurs at the site of unsaturation in a molecule. Thus, compounds having multiple bonds such as

Undergo addition reactions. The reactivity of these compounds is due to the more exposed and easily available  electrons to the electron-seeking (electrophilic) reagent. (i) Electrophilic addition reaction This is a characteristic reaction of unsaturated hydrocarbons, e.g.

Both the reactants add to form a single product. Mechanism The machanism of the reaction is based on the following observations. (i) When ethylene is brominated in aqueous solution in the presence of sodium chioride, the product in addition to ethylene dibromide contains 1-chloro-2- bromoethane.

This indicates that a carbocation formed in the first step is attacked by both Br   (From Br2) and Cl (present in solution) in the second step. (ii) On bromination trans-2-butene given meso-dibromide and cis-2-butene gives racemic (DL) modification. This indicates addition of bromine atoms to the  bond from opposite sides of the plane of the ethylene molecule i.e., trans-addition results. On the basis of the above observations, the following mechanism is suggested for addition of bromine. On the approach of the two reactants the Br – Br bond is polarized by the  electrons to form a  complex which breaks down to form a cyclic bromonium ion and the other bromine atom leaves with the bonding pair of electrons in the first step. In the second step the bromide ion attacks either

131

of the carbons (originally) double-bonded from the opposite side to complete the addition. This results in trans-addition.

On the basis of the formation of bromonium ion, the formation of meso-dibromide from trans-2-butene and racemic dibromide from cis-2-butene on bromination can now be explained.

132

The reaction is therefore stereoselective. Evidence for the formation of intermediate carbocation in the first step is provided by the formation of abnormal product (14) along with the expected product (15) when 3-methyl-1-butene is treated with halide. The abnormal product is due to the inherent characteristics of rearrangement of carbocations for stability.

Hence, the bromonium ion may be considered as a resonance hybrid of the following canonical forms, i.e., an alternative canonical form of the carbocation.

The first step of the reaction is slow due to polarisation of bonds, formation of  complex and bromonium ion or carbocation. In contrast, the second step is fast due to attraction between oppositely charged ions. Since the slowest step is initiated by electrophile and the overall reaction is addition, the reaction has been classed as ‘electrophilic addition’. Effect of substituents It is seen that a bormonium ion or a carbocation is formed in the rate- determining step. Elctron donating substituents enhance the rate of electrophilic attack and also aid to stabilize the carbocation. Thus, the activation energy for the formation of the carbocation is lowered so that the reaction becomes fast. The relative rates of addition of some substituted alkenes are.

133

Obviously, electron-withdrawing groups will have reverse effect. Markovnikov rule: In case of addition of unsymmetrical reagents (e.g., HX) to unsymmetrical alkenes, the negative moiety (i.e., nucleophile) of the addendum (reagent) attacks the more highly substituted carbon. This is know as Markovnikov rule. Thus, addition of HBr to propylene gives 2-bromopropane (16) and not 1- bromopropane (17).

Markovikov rule is explained on the basis of the stability of the first formed carbocation. Since 2 carbocation is more stable and hence formed more easily than 1 carbocation, the product is (16). Thus, when more than one carbocation formation is possible, the most stable of the carbocations will determine the orientation of the overall addition. This is seen in the addition of HCl to vinyl chloride when ethylidene chloride (18) and not ethylene chloride (19) obtained.

The rate of addition is, however, slower (about 30 times) than with ethane due to the electron-withdrawing effect of chlorine. Free Radical Addition In the presence of peroxide or under conditions of radical formation, anti- Markovnikov addition results. The peroxide breaks down to a free radical which generates a bromine-free radical from HBr. The bromine radical attacks the  electrons producing a 2 radical rather than a 1 radical for reasons of stability.

134

Free radical addition of HF, HI or HCl is energetically unfavourable. Addition to conjugated dienes: Conjugated dienes, e.g., 1,3-butadiene, undergo electrophilic addition in a similar stepwise process. However, more than one addition product is formed. This is due to the preferential formation of a resonance –stabilized allylic carbocation in the first step in which the positive charge resides of both C2 and C4 either of which can be attacked by the nucleophile in the second step to result in 1,2, and 1,4-addition product.

The 1,2-product predomination at lower temperature and 1,4-product predominating at higher temperature. This may be due to stabilization of 1,4- product by hyperconjugation. Addition to alkynes Electrophilic addition to alkynes resembles those of alkenes. For example, one molecule of bromine adds first to acetylene in two steps to give trans 1,2-dibromoethyllene and then another molecule of bromine adds to give 1,1,2,2-tetrabromoethane.

However, alkynes are less reactive than alkenes because the  electrons are more tightly held by the carbons due to their relative short distance between the carbons

135

(1.20 A for C  C and 1.34 A for C = C). This is reflected in the hydration of alkynes with sulphuric acid in which the aid of a catalyst (mercuric salt) is necessary (20).

Aromatic compounds (e.g., benzene) have  electrons which are tightly held by several nuclei. Aromatic compounds are therefore much less reactive and undergo a few addition reaction. It is more so because addition reaction is energetically unprofitable due to loss of resonance energy. (ii) Nucleophilic addition reaction We have seen that electron-releasing groups conjugated to carbon-carbon multiple bonds promote electrophilic addition. In the same way, conjugation of electron- withdrawing groups activate the carbon-carbon multiple bonds towards nucleophilic addition.

The substituents reduce the -electron density, thereby aid the attack of the nuclophile and stabilize the carbanion formed on attack by delocalization of the negative charge. Some common electron-withdrawing groups are.

Polar functional groups, e.g., > C = O, - CN, > C = N, > C = S, etc., also undergo nucleophilic addition. The hetero atoms, like the electron-withdrawing substituents, reduce the -electron density on the carbonyl carbon and stabilize the anion, formed on attack of the nucleophilic, by accommodating the-ve charge.

However, the addition product will be stable enough to be isolated provided the carbonyl group is not attached to a good leaving group such as OH, OR, Cl, NH2,

136

etc. Carboxylic acids and their derivatives, therefore, undergo substitution nather than addition on attack of nucleophiles. Nucleophilic addition to carbonyl group is, therefore, a characteristic reaction of aldehydes and ketones since H, R and Ar are not good leaving groups. Considering the steric and electronic factors (inductive effect) of the group attached to the carbonyl carbon, the reactivity of the carbonyl groups decreases in the order. H2C = O > RCHO > R2CO > ArCHO > Ar2CO. Hydroxylation Hydroxylation of alkenes to yield diol can be carried out with a large number of reagents of which Osmium tetroxide, OsO4 and alkaline potassium permangnate, KMnO4 solution are important. Both these hydroxylations are stereoselectively syn addition and the product in either case is a cis-diol which is evidenced from the following examples. In order to explain the stereoselectivity syn addition in both the cases, formation of cycle intermediates as depicted below has been suggested.

Osmium tetroxide reacts slowly but almost quantitatively and the cyclie intermediate has been isolated. This cyclic intermediate is decomposed with sodium bisulphite in ethanolic solution. The major drawback of this reagent is that it is expensive and toxic in nature and so it is used for small scale preparation.

However, this drawback may be avoided by using H2O2 as catalyst. H2O2 re- oxidises the reduced compound the osmic acid OsO2 (OH)2 to OsO4 minimising thereby the costing. In the case of permanganate there is also formation of cyclic intermediate which in presence of alkali undergoes cleavage forming glycol. But since KMnO4 is stronger oxidising agent than OsO4 it can oxidise the glycol

137

formed to yield ketone or carboxylic acid and it is quite difficult to stop the reaction at the diol stage i.e.,

The borane (BH3) exists as the gaseous dimer, diborane (B2H6). Diborane is commercially available in the form of complexes with THF and can be prepared from sodium borohydride and boron trifluoride.

3NaBHBF343426+⎯⎯→+ NaBF2BH Hydroboration of olefins Mechanism The addition of B-H unit to double bond involves a simple four center transition state. Boron being electron deficient begins to add to the double bonded carbon. The reaction unlike ordinary electrophilic addition, does not proceed to give a carbocation, because the carbon that is losing the -electrons, begins to take one of the hydrogen attached to boron, with its electron pair, Thus, in the transition state both the boron and hydrogen add to the double bonded carbons shown below.

Hydroboration unlike ordinary electrophilic addition, proceeds without skeletal rearrangement at normal temperature because carbocations are not formed as the intermediates. Thus, 3,3-dimethyl-1-butene (1) on hydroboration followed by its oxidants yields the expected 3,3-dimethyl-1-butanol (2) and not the rearranged product (3).

138

Grignard reagents The organomagnesium halides are known as Grignard reagents. The Grignard regents are represented as R-Mg-X, where R = alkyl, alkenyl, alkynyl or aryl group and X = Cl, Bro or I.

139

Nucleophilic Addition Reactions of carbonyl group The carbonyl group of aldehydes and ketones is a highly polar group. It may be represented as:

The positively charged carbon is readily attacked by electron-rich nuclophiles. The negatively charged oxygen is attacked by electron-deficient electrophiles.

Aldehydes and ketones undergo nucleophilic addition reactions by the following general mechanism. Step 1: The nucleophile (Nu:-) attacks the positively charged carbonyl carbon to form a new bond. As the new bond is formed, -bond between the carbon and oxygen is broken. The electron pair goes to oxygen, which acquires a negative charge.

140

Step 2. The electrophile (e.g., H+) attacks the negatively charged oxygen to form the addition product.

The nucleophilic addition reactions of carbonyl compounds may be catalyzed by acids or bases. Base-Catalyzed Addition. Bases convert a weak neutral nucleophile to a strong one by removing a proton. The strong nucleophile then adds to the carbonyl group as shown above.

Acid-Catalyzed Addition. The acid-catalyzed nucleophilic addition occurs by the following mechanism. Step 1: The hydrogen ion from the acid attacks the negatively charged carbonyl oxygen to give protonated carbonyl group. The protonated carbonyl group is resonance stabilized.

Step 2: The nucleophile attacks the protonated carbonyl group to form the addition product.

141

Notice that the addition product is the same whether the reaction is acid- catalyzed or base-catalyzed. The nucleophile always adds to the carbonyl carbon and the proton (electrophile), to the oxygen. Generally ketones are less reactive than aldehydes in nucleophilic addition reactios. 2. Reaction with carbonyl compounds (Nucleophilic addition reactions) The C-Mg bond in Grignard reagent is polar and generates a nucleophilic carbon (viz., C- -Mg+ - Br) compared to normal bond polarization of the C-Br bond which generates an electrophilic carbon (C+ - Br-). This ability to invert the polarity of a carbon atom allows the Grignard regents to function as a carbon nucleophile. In fact this is an example of reverse polarization (as in the phenomenon of Umpolung). The main use of the Grignard reagent is as a carbanion, usually in reactions with carbonyl compounds.

Being nucleophilic in nature, the Grignard reagents attack the carbonyl group of aldehydes, ketones, esters, anhydrides, acid chlorides, and amides. In this reaction the alkyl group having carbanionic character becomes attached to the carbonyl carbon and the magnesium halide to the oxygen of the carbonyl group to give a complex (addition product). These addition products on decomposition with water give the hydroxy compounds (alcohols). The reactions with various carbonyl compounds are given below. (i) Reaction with aldehydes Grignard reagents react with aldehydes to give addition products, which on hydrolysis give secondary alcohols.

142

However, formaldehyde (being an exception) given primary alcohol.

There are however, some instances where the reaction between an aldehyde and a Grignard reagent gives a keton and a primary alcohol, probably by a hydride transfer.

(ii) Reaction with ketones The ketones on reaction with Grignard reagents and subsequent hydrolysis give tertiary alcohols.

In case of cyclic ketones (e.g., cyclohexanone) the reaction take place as given below.

143

In the above reaction, the formed carbinol on treatment with H2SO4 looses a molecule of water to give the corresponding cyclohexene, which on reaction with per acid gives the epoxide.

This reaction takes place by a hydride transfer from alkyl group of the Grignard reagent involving a six-membered cyclic transition state.

The above reaction is similar to Meerwein-Ponndorf-Verley reduction.

144

(iii) Reaction with esters

(iv) Reaction with acid chlorides Acid chlorides react with Grignard reagent to give ketones, which may react with excess of the reagent to produce tert-alcohols.

(v) Reaction with acid anhydrides Grignard reagents react with acid anhydrides to give addition products which on hydrolysis give tertiary alcohols.

(vi) Reaction with amides The amides on treatment with Grignard reagent give addition products, which on hydrolysis give ketones.

145

Similarly, dimethylformamide and dimethylacetamide on reaction with a Grignard reagent give corresponding carbonyl compounds in excellent yield.

Addition of Grignard reagent to carbon-carbon double bond

In case of , -unsaturated aldehydes (e.g., crotonaldehyde) there is no hindrance at the C=O group and the product formed (major) is unsaturated alcohol.

146

Organocopper compounds The organocopper reagents that are particularly useful, are prepared by transmetallating the Grignard reagent or organolithiums.

The organocopper reagents with the general formula R2CuLi are called lithium organocuprates or lithium dialkylcuprates. These are prepared from alkyl halides (e.g, CH3CI) by first converting into alkyl lithium (CH3Li) followed by treatment with Cu(I) salts. Just as with Grignard reagent, the exact structure of R2 CuLi is not clear.

Organocopper reagents are less stable and are prepared in situ. Organocopper reagents are highly selective towards different functional groups and this selectivity is a major factor in determining their usefulness. The organocopper reagents are referred to as Gilman reagents. 1. Reaction with alkyl or aryl halides (Coupling reactions)

147

2. Reaction with epoxides Organocopper reagents react with the epoxides. The epoxide is attacked at the least substituted carbon atom giving the corresponding alcohol.

3. Reaction with acid chlorides The acid chlorides react with organocopper reagents to give the corresponding ketones.

ArCOCl + (CH3)2 CuLi → ArCOCH3 4. Reaction with , -unsaturated carbonyl compounds The lithium organocuprates react with , -unsaturated carbonyl compounds giving exclusively the 1,4-addition product (conjugate addition). The utility of organocopper compounds is also illustrated in the following reaction.

The utility of organocopper compounds is also illustrated in the following reaction

148

Benzoin condensation The self-condensation of aromatic aldehydes (with no -hydrogen) in presence of cyanide ions as a catalyst to -hydroxy ketone (benzoin) is called benzoin condensation. Benzoin belongs to a class of compounds called acyloins. The reaction is not successful with aliphatic aldehydes under these conditions.

Mechanism Cyanide ions attacks the carbonyl group to give (1). Cyanide group with its electron withdrawing nature makes aldehydic hydrogen more acidic. The conversion of (1) to (2) is favourable because the ion (2) is stabilised by both the benzene ring and the cyanide group. The anion (2) attacks another aldehyde carbonyl to form the link between the two molecules. The deprotonation- protonation steps give the alkoxide anion. (3). Finally, cyanide ion departs from (3) to give benzoin.

149

Applications Anisaldehyde and p-tolualdehyde give the corresponding -hydroxy ketons. Similarly furfural gives furoin.

Knoevenagel condensation The condensation of aldehydes or ketones, having no -hydrogen atom, with active methylene compounds (especially malonic ester) in presence of a very weak base like ammonia or amine (primary or secondary) is known as Knoevenagel condensation.

Mechanism The Knoevenagel reaction is reversible and normally the equilibrium lies towards left and the yield of the product is low. However, Cope introduced an important procedure for carrying out the reaction in benzene and removing the water formed as an azeotropic mixture in Dean Stark apparatus, thus shifting the equilibrium completely towards right. Such type of Knoevenagel reaction is known as Cope-Knoevenagel Reaction.

150

Applications This reaction is of great synthetic importance because a large number of , - unsaturated compounds can be synthesised by using this reaction. Some applications of Knoevenagel condensation are given below. Stobbe condensation This is a condensation between dialkyl succinates and aldehydes or ketones in presence of base like sodium hydride, potassium tert-butoxide or sodium ethoxide to form salts of ,-unsaturated half esters. Benzaldehyde condenses with diethyl succinate in the presence of base to produce the salt of ethyl -benzylidene ester of succinic acid. Mechanism

Application Some important applications are given below.

Darzens glycidic ester condensation When condensation of aldehydes or ketones with -haloester takes place in the presence of a base, ,-epoxy esters called glycidic esters are obtained. These glycidic esters are useful intermediates for the synthesis of aldehydes or ketones. The base used in this reaction is potassium tert-butoxide (a hindered

151

base) to avoid the SN2 displacement of the chloride. For example, ethyl chloroacetate on condensation with acetophenone in the presence of base produces ,-epoxy ester (1).

Mechanism The reaction involves the addition of the carbanion (2) to the carbonyl group of aldehyde or ketone to give an oxyanion (3). The displacement of the halide ion takes place by an internal SN2 reaction.

The glycidic ester obtained by above method on alkaline hydrolysis given glycidic acid, which undergoes decarboxylative rearrangement in presence of acid to give an aldehyde or a ketone.

Applications Some important applications are given below.

152

Reformatsky reaction The reaction of -haloesters (usually -bromoesters) with carbonyl compounds such as aldehydes and ketones in presence of zinc in an inert solvent (ether-benzene) to produce -hydroxyesters is known as Reformatsky reaction.

Dehydration can be achieved by distillating -hydroxy esters with a trace of iodine. Machanism The reaction involves the formation of an intermediate organzinc compound which then adds to the carbonyl group. The resulting complex is readily hydrolyzed to -hydroxy ester.

153

The zinc is preferred to magnesium since the organozinc reagent is generally less reactive than the corresponding organo magnesium reagent and later reacts with ester group. Propargyl bromide and -haloamides may be substituted for -halo esters in the Reformatsky reaction.

Applications Reformatsky reaction has important applications in organic synthesis.

4.2 Elimination Reactions When two groups or atoms from adjacent carbons are eliminated with the formation of unsaturated compounds (alkene or alkyne), the reaction is called elimination reaction. Most commonly a nucleophile (from the -carbon) and a proton from the -carbon are eliminated. Hence, the reaction is known as 1, 2-or , -elimination or simply -elimination.

Some familiar elimination reactions are: (i) Dehydrohalogenation of alkyl halides by base.

(ii) Dehydration of alcohols by acids.

154

(iii) Hofmann’s degradations of quarternary bases by heat.   RCHCHN−−−⎯⎯→−=++223232 ROHRCHCHR NH O The presence of at least one hydrogen on the -carbon is necessary for elimination. The driving forces for elimination are (a) stability of the olefin formed and (b) the relief form steric strain due to crowding in the substrate. Branching at the -carbon (as also at the -carbon) of the substrate produces substituted olefins stabilized by hyperconjugation and hence favours elimination.

Thus, Me3CCl gives only 16% olefin while Me2CH – CMe2Cl gives 62% olefin. Strain in the substrate due to crowding by the substituents can be relieved on the formation of olefin since the bond angles increase from 109.5 in the substrate (sp3-hybridized) to 120 in the product (sp2-hybridized). Hence 3 halides favour elimination most and 1 halides the least, i.e., the order of elimination in halides is 3 > 2 > 1. The elimination reactions like SN reactions may proceed by either unimolecular or bimolecular mechanisms. These elimination reactions have been designated E1 1 2 and E2 on their resmblance to SN mechanism and SN mechanism respectively. (a) E1 mechanism. The elimination reaction in which the rate of reaction is dependent on the concentration of the substrate only, i.e., kinetically of the first order, is designated E1. Since the rate of reaction is independent of the concentration of the reagent, it is interpreted, as in SN1, that the first step of the reaction is the slowest step involving ionization of the substrate. This is followed by the rapid removal of a proton from the -carbon by the reagent is the second step. This is illustrated below. (i) Dehydrohalogenation of alkyl halides-The rate of elimination of a haloacid from t-butyl bromide in basic medium is found to be proportional to [Me3CBr]. Therefore, the halide undergoes slow ionization in the first step. This is followed by a rapid extraction of a proton from the carbocation by the base or solvent in the second step.

155

It is seen that a carbocation is formed in the step in both E1 and SN1 reactions. Hence, the reagent can attack the carbon to give substitution product and also can accept a proton to give elimination product. In practice both alcohol (substitution product) and alkene (elimination product) are obtained on hydroysis of Me3CBr.

When more than one alkene can be formed, that alkene will predominate which has larger number of alkyl groups on the double-bonded carbons-this is Saytzev’s rule. This is understandable since the substituted alkyl groups will stabilize the alkene by hyperconjugation.

(ii) Dehydration of alcohols-Acid-catalysed dehydration of alcohols follows E1 mechanism. The dehydration is carried out at elevated temperature with sulphuric acid. Alcohol is first protonated which weakens the C-O bond. Hence, water is eliminated from the protonated alcohol with generation of a carbocation. The latter then expels a proton to form a stable alkene.

156

The concentration of acid depends upon how fast the carbocation is formed, i.e., on the stability of the carbocation. Primary alcohols generate unstable carbocations and hence require high temperature and high concetration of acid while 3 alcohols require lower temperature and lower concentration of acid for dehydration. Thus, CHCHOHCHCH⎯⎯⎯⎯→=concH24 SO 3222 170 C CH3 | CH C OH⎯⎯⎯⎯→20%H24 SO CH − = C CH ( 3)3 ( ) 90 C 3 2

E1 reaction is facilitated by i) branching at the -and -carbons of the substrate for stability of the olefin, ii) strong polar solvent to aid ionization. iii) low concentration of base the greater stability of the alkene over the carbocation makes the extraction of proton easy. (b) E2 mechanism. When the rate of elimination reaction is dependent on both the substrate and the reagent, i.e., rate  [substrate] [reagent], the reaction is kinetically of the second order or bimolecular. Such bimolecular elimination reaction is designated E2 on its similarity with SN2. The reaction occurs in one step in which both the groups (proton and the leaving group) depart simultaneously through the intermediate transition state. It is visualized that as the base abstracts a proton from the -carbon, simultaneous departure of the nucleophile takes place from the -carbon.

157

The energy of the transition state will be least when the two leaving groups, the -and -carbons and the attacking base are coplanar in the transition state. Also, the two leaving groups (H and X) should be trans to each other to effect  bond. The two leaving groups orient themselves in the trans position when a  bond exists between the -and -carbons. Thus, acetylene dicarboxylic acid is more easily formed from chlorofumaric acid (25) than from chloromaleic acid (26).

E2 reaction is facilitated by i) branching at -and -carbons-since more stable olefin is formed. ii) strong base of high concentration-since a strong C-H bond has to break, iii) solvent of low polarity-polar solvents from a strong solvent wall around the base restricting the attack. Hence DMF or DMSO are usually used as solvents. (c) E1 cB mechanism. It may be argued that second-order elimination reaction may as well proceed in two steps as in E1 reaction. The first step involves a fast and reversible removal of a proton from the -carbon with the formation of a carbanion which then loses the leaving group in the second slow rate-determining step.

The overall rate of this reaction is thus dependent on the concentration of the conjugate base of the substrate (carbanion). Hence, this mechanism has been designated as E1cB (Elimination, Unimolecular from conjugate base).

158

To distinguish between E2 and E1cB mechanisms, deuterium exchange experiment was performed. For this 2-phenylethyl bromide was treated with sodium ethoxide in EtOD. This substrate was selected because the Ph group is expected to increases the acidity of the -hydrogen and also to stabilize the carbanion to exist long enough for incorporation of deuterium in the starting material from the solvent EtOD.

The reaction was interrupted before completion and analysed for deuterium content. No deuterium incorporation was found either in the substrate or in the styrene. Hence, no reversible carbanion was formed. The reaction followed E2 path. However, the E1cB mechanism does operate in substrates having strong electron-withdrawing groups, e.g., chlorine on -carbon, and poor leaving groups, e.g., fluorine as in Cl2CH-CF3. Elimination vs substitution Elimination reactions are usually accompanied by substitution reactions. When the reagent is a good base, it accepts protons to yield elimination products (alkenes) and if it is a good nucleophile then it attacks the carbon to give substitution products. The proportion of elimination and substitution depends upon the following. (i) Structure of the substrate-In general, the proportion of elimination increases with increase in the branching of the carbon chain. In other words, the proportion of elimination increases from 1 → 2 → 3 substrates. The reason is that alkenes formed on elimination are stabilized by hyperconjugation. Also the steric strain due to crowding in the substrate (sp3-hybridized, bond angles 109) is relieved on the formation of alkene (sp2-hybridized, bond angles 120) whereas on substitution the strain is reintroduced. Suitably substituted groups, e.g., C = C and Ph, in the substrate that can stabilize the developing alkene favour elimination. Thus, ethyl bromide gives about 1% alkene while 2-phenylethyl bromide gives about 99% styrene. (ii) Nature of the base-Strong bases promote elimination over substitution in general, and in particular E2 over in non-polar solvents favours E2 over SN2.

159

Hence, alcoholic KOH favours elimination and aqueous KOH favours substitution. Strong nucleophiles but weak bases promote substitution over elimination whereas strong bases but weak nucleophiles promote elimination over substitution. Elimination increases with increase in the size of the nucleophile. (iii) Nature of solvent-For most reactions, increasing solvent polarity increases the rate of SN1 reactions and decreases SN2 reactions. Hence, the pathway can be changed with changing polarity of the solvent. A less polar solvent not only favours bimolecular reactions but also E2 over SN2. Change of hydroxylic solvents to aprotic solvents increases the base strength as the solvent layer around the base  by hydrogen bonding is absent. Thus, Cl ,OH, OR, etc., are very strong bases in DMF (dimethylformamide) or DMSO (dimethyl sulphoxide). The use of aprotic solvents may sometimes changes the pathway from E1 to E2. (iv) Effect of termperature-In elimination reaction a strong C-H bond has to break, hence a high-activation energy is required for elimination reaction rather than for substitution reaction. In general, the proportion of elimination increases on using a strong base of high concentration and a solvent of low polarity. On the other hand the proportion of substitution increases by using a weak base of low concentration and a solvent of high polarity. Competition between substitution reaction and elimination reaction Besides undergoing substitution reaction, another common reaction of substrate is an elimination reaction where nucleophile acts as a base to remove HX instead of adding to the substrate. Elimination can therefore, compete with substitution. Many factors influence the extent of this competition, including the nature of nucleophile, its strength, the solvent and the substrate. The strong bulky Bronsted bases favor E2 and strong nucleophiles favor SN2 process. For instance, - bulky tert-butoxide anion (Me3CO ) can abstract a proton from the periphery of the molecule but is hindered as a nucleophile. However, some anions such as thiol - anion (RS ) are less basic and more strongly nucleophilic. The E2 : SN2 ratio increased substitution by alkyl groups. Primary alkyl halides will usually undergo

SN2 substitution reaction in preference to E2 elimination reaction. As base strength increases, the rate of competitive elimination will increase, but substitution reactions compete when the base is also a good nucleophile. Polar aprotic solvents are used to maximize the yield of SN2 products and suppress side reactions such as elimination.

160

The E1 and SN1 involve the formation of the same intermediate, carbocation, by the same rate-controlling ionization step. However, the course of the reaction can often be controlled by specific reaction conditions. A high concetration of nonbasic nucleophiles in aqueous media favors the unimolecular substitution (SN1), whereas unimolecular elimination (E1) processes are favored with bases of weak to moderate strength that are also poor nucleophiles. In geeneral, unimoleular substitution is faster than unimoluecular elimination, since the cationic carbon is more strongly attracted to the electron-rich center.

Orientation in elimination reactions Substrates having alternative -hydrogens give a mixture of olefins on elimination.

To help in forecasting the major product of elimination (alkene), there are two empitical rules: (i) Saytzev rule and (ii) Hofmann rule. (i) Saytzev rule-The rule states that neutral substrates (alkyl halides, alkyl toluenesulphonates) lead predominantly to that alkene which is more highly substituted on the carbons of the double bond. In E1 mechanism the group is gone before the abstraction of proton. Hence the direction of elimination depends wholly on the relative stabilities of the olefins. Therefore, Saytzev rule governs the orientation of E1 reaction.

In suitable substrates the rearrangement of the carbocation before elimination may give different alkenes. For steric reasons the non-Saytzev product may be the major product in suitable substrates.

161

The olefin obtained through path (b) is minor due to steric hindrance. In E2, it is suggested that the incipient olefinic bond formation in the transition state is being stabilized by the inductive effect of the alkyl groups, thereby lowering the energy of the transition state. Therefore, with the increasing number of alkyl groups there will be increasing stability of the transition state with progressive lowering of energy of the transition state.

(ii) Hofmann rule-When a quaternary ammonium hydroxide is strongly heated (<125C) it decomposes to yield a tertiary amine water and alkene.

This is known as Hofmann elimination or -elimination. The reaction involves abstraction of a proton from -carbon with the simultaneous expulsion of the leaving group.

162

When there are alternative -hydrogens in the quaternary ammonium salts, a mixture of alkenes is formed. Thus, 2-butylquatermary ammonium hydroxide undergoes Hofmann elimination to give 1-butene as the major product.

To explain, it has been suggested that the strong electron-withdrawing

 effect of Me3 N group makes the hydrogens of the -carbons more acidic for facile abstraction by the base and stabilizes the incipient carbanion formation in the transition state on gradual stretching of the  C-H bond. In this particular compound with alternative -hydrogens, the -hydrogens are less acidic due to +l effect of the adjacent methyl group. Hence, ’-hydrogen which is relatively more acidic is removed to give predominantly l-butene. Hofmann product increases on increasing branching in the base. Steric effect due to crowing in the leaving group or in the substrate promotes Hofmann elimination. In general the proton acidity and for that matter the inductive effect is the more important factor for Hofmann elimination. Whatever be the conditions, that alkene is formed in which its double bond is conjugated with Ph or C = C groups, e.g.,

Hofmann elimination has been very useful in the degradation of nitrogeneous heterocyclics for structure determination. Thus,

163

Stereochemistry of E2 Elimination results in -bond formation. In E2 reaction the p orbitals which develop on the -and -carbons with the departure of the leaving groups should be parallel for maximum overlap. For this both the leaving groups should be parallel for maximum overlap. For this both the leaving groups and the carbons bearing them should be in one plane. When the two leaving groups are planar there can be two extreme conformations: (a) anti-periplanar (27), i.e., the two groups are in trans position and (b) syn-periplanar (28), i.e., the two groups are in cis position. The elimination then may proceed as given below.

From the Newman projections of the trans and cis conformation the elimination is expected to be more facile from the trans conformation (27a) than from the cis conformation (28a). This is because (i) in (27a) the attacking base approaches from the farthest side of the leaving group while in (28a) the attack is from the same side of the leaving group which causes repulsion, (ii) the developing charge on the -carbon displaces the leaving group with its bonding pair from the back side (as in SN2), a path of least energy, and what is most

164

important is (iii) the elimination occurs from the lower-energy staggered conformation (27a) than from the higher-energy eclipsed conformation (2a). Hence, the transition state and consequently the pathway for elimination is of lower energy when the leaving groups are trans (27) than when they are cis (28).

Therefore, most E2 reactions proceed faster when the leaving groups are trans (25) then they are cis (26). The -isomer of hexachlorocyclohexane has all the six chlorines in the equatiorial bonds so that they are all trans to each other and no hydrogen is available in the trans position. The result is that the eliminaton of HCI is slower by 7000-24000 times in -isomer than in other isomers.

Examples of E1-reactions (a) Dehydration of ethyl alcohol by concentrated sulphuric acid at a temperature of 180 yielding ethylene is an example of E1 reaction. This reaction takes place through the following steps.

That, it is really and E1 reaction is established from the fact that there is the formation of ethyl hydrogen sulphate as an intermediate. The formation of this intermediate is a clear indication that there is formation of the necessary carbocation required for its generation as shown below.

165

When this ethyl hydrogen sulphate is heated at a temperature of 180 desired ethylene is formed.

(b) Dehydrobromination of tert-butyl bromide by the action of strong solution of alcoholic potash constitutes another example of E1 example.

Example of E2 eliminations As stated above E2 elimination reactions are extremely common and most of the elimination reactions frequently encountered are E2 elimination reactions. Thus, (a) Formation of alkene by dehydrohalogenation is one of the most important example.

(b) Decomposition of quarternary ammonium compound by alkali is also an example of E2 reaction.

166

Cis (syn)-elimination reaction Although trans elimination is the most common elimination reaction yet under certain conditions cis (syn) elimination reactions have been found to occur. In such conditions necessary orbital overlapping requirement of E2 elimination may be fulfilled for cis elimination of the molecule is planar and 0 dihedral angle does not stand in the way of elimination reaction. The bridged head cyclic compounds like bornane compounds constitute the most significant examples of syn-elimination. Thus,

Pyrolytic elimination (cis-elimination) There are a few example of pyrolytic elimination which takes place through cis elimination of the departing groups (-H and nucleophile). The characteristic feature of this type of elimination is that these reactions are intramoleular in nature and is sometimes expressed as Ei. Some of the examples of pyrolytic cis (syn) elimination reaction are depioted below. (a) Chugaev reaction: Pyrolysis of xanthates and carboxylic esters results in the formation of alkene and is generally known as chugaev reaction. These reactions normally proceed through the formation of a planer six-membered cyclic transition states. Thus,

167

(b) The Cope reaction: In this reaction tertiary amine oxide is heated when alkene is formed. Thus,

This reaction has been suggested to occur through the formation of a planar five membered cyclic transition state. It may be mentioned that Cope reaction exhibits highest degree of syn stereo-selectivity among the pyrolytic elimination reactions.

Cope reaction is also a stereospecific reaction which is evident from the following reactions.

168

Pyrolysis of a quaternary ammonium hydroxide salts, derived from an amine having alkyl group that is larger than the methyl group, gives an olefin and a tertiary amine. This type of elimination reaction is known as the Hofmann elimination reaction.

Mechanism

Some other applications of Hofmann elimination are given below.

169

Bredt's rule The Bredt’s rule states that a bridged bicyclic compound cannot have a double bond at a bridgehead position unless one of the rings contains atleast eight carbon atoms. Norbornene is a stable compound, since the double bond is away from the bridgehead carbon, however, its isomer with a bridgehed double bond is unknown. When however, the number of ring atoms is larger in which the ring strain (the cause of non-formation of bridgehead double bonds) is lower, the presence of a bridgehead double bond is possible. During -eliminations in bicyclic systems, the bridgehead atoms are not involved, provided the ring bearing the incipient “trans” double bond has at least eight atoms.

170

Exercise

1. Write note on the mechanisms of (i) Benzoin condensation (ii) Knovenagel condensation (iii) Darzens glycidic ester condensation (iv) Reformatsky reaction (v) hydroxylation reaction (iv) hydroboration 2. List out the synthetic applications of (i) Grignard reagents (ii) Dimethyllithiumcuprate 3. Give an account of stereochemical factors influencing the addition of bromine and hydrogen bromide 4. Write note on (i) E1, E2, E1cB mechanisms (ii) Hofmann rule (iii) Saytzeff rule (iv) Hofmann degradation (v) Cope elimination (vi) Bredts rule (vii) Chugaev reaction (viii) Dehydrohalogenatio (ix) Pyrolyic elimination

171

Unit – V 5.1 Photochemistry Introduction In general, energy must be supplied to the reacting molecules to initiate a chemical reaction. This is true even though the reaction equilibrium lies completely in the forward direction. When such additional energy is provided by light, usually known as radiant energy, the reaction is termed as photochemical reaction. In these reactions, the energy is introduced in the reacting system by the absorption of electromagnetic radiation in the ultraviolet and visible region. But if the energy is supplied by heating the reactants i.e. by increasing the temperature of the reaction, the reaction is usually designated as thermal reaction. Difference between thermal and photochemical reactions The most basic difference between photochemical and thermal reaction lies in the fact that in thermally activated reactions, the reactants are at their ground electronic states and the energy entering into the system in the form of heat is distributed among all the molecules of the system according to the statistical principle. On the other hand, in photochemical reaction molecules are not in the ground electronic state. In this reaction individual molecules are promoted to highly excited forms without immediate effect on the surrounding molecules. This selective excitation of individual molecules imparts an unique character to photochemical reactions. The chemical nature of the exicited molecules is different from those in the ground state and so it is obvious that the course of the reaction may often be different for these two processes. Another important difference between these two kinds of reactions is that generally very high temperature is used during a thermally induced reaction. In these reactions, short lived free radicals or molecular fragments are generated while in photochemical reactions specific bond cleavage may be brought about at any desired initial temperature of the reactant molecules. As a rule, only those thermochemical reactions are possible which are associated with the decrease in free energy (negative G) but the photochemical reactions in many cases are accompanied with the increases in free-energy (positive G). Again, as with the rise in temperature, number of effective collisions increases, thermal reactions are affected by the change in temperature of the reactants. The rate of photochemical reaction is independent of the temperature-it only depends upon the intensity of light absorbed.

172

Principle of Photochemical Reaction Absorption of energy As mentioned earlier, in photochemical reactions a molecule becomes energy activated to an excited state by the absorption of electromagnetic radiation in visible and uv region. This process of absorption of energy is a quantised process and molecules absorb energy in terms of quantum of energy (photon) which is given by Planck’s expression, E= h  = h cc  = .  where E is the energy per quantum, h is the Planck’s constant = 6.631027erg. sec.  = frequency of radiation  = wavelength c = velocity of light = 31010 cm/sec. From the above expression it is evident that the frequency and wavelength are inversely related. The energy absorbed per mole at a specific wave length may be calculated from the following equation. E = Nh where N is Avogadro’s number = 6.021023 6.63 1erg.sec −272310  6.02 103 10. cm or Eh.N.==c sec  (nm) 2.8610 4 Kcal or E = mole (nm) The wave length range of visible and ultra violet region is 200-800 nm and the corresponding energy range is 35-150 Kcal/mole. This energy range is much higher than covalent bond dissociation energies and so they can induce chemical changes by exciting the molecules to higher electronic state. Electronic transition When a molecule absorbs light in the visible and ultra violet region electronic transition occurs. In organic molecules there may be three types of electrons. (i)  → * (ii)  → * (iii) n → * (iv) n → *

173

The energy level for different types of transition may be indicated by the following diagram.

Of these,  → * transition requires much more energy than available in visible and uv region and so normally this transition does not occur in these regions. Fate of molecules in excited states Most of the organic molecules have all electrons paired and molecular states with all electrons paired are called singlet states (S0). When excitation occurs, paired electrons become unpaired and two unpaired electrons exist in different orbitals due to promotion of one of the paired electrons to the antibonding orbiral. Absorption of light with correct required energy may occur without inversion of spin and so the electron spins remain as before i.e. paired in the excited state. This state is commonly termed as excited singlet state represented by S1, Sometimes, it may so happen that the electronic excitation is followed by spin inversion giving rise to a new excited state with two unpaired electrons. This excited state is known as excited triplet state (T1). It may be mentioned that direct excitation of the ground state (S0) to a triplet state (T1) is not possible and T1 is always occurs through S1. The terms singlet and triplet have been derived from the fact that the singlet states do not split in a magnetic field where as triplet states split into three different energy levels. The above processess may be indicated by the following diagram. Dissipation of energy (Jablonski’s Diagram) After absorption of energy following major events may take place a) The molecule may be excited to higher vibrational level S0 from S2

174

-11 b) The life time of S2 is less than 10 second and so rapidly decays to lower excited singlet state S1. This conversion of S2 to S1 (from higher excited to lower excited singlet states) is called internal conversion or vibrational cascade. -8 c) The life time of S1 is the longest of all excited states (10 sec). It loses energy in any one of the following manners. i) it may emit energy as a photon and drops to S0. This process is termed as fluorescence. ii) it may drop to S0 by a non-radiation process in which excess energy of the excited state is mixed with vibrational modes. iii) it may undergo chemical reaction and iv) it may drop to T1 (triplet state). It is a slow process. It may be mentioned that

T1 state is a stable state but S1 → T1 is a forbidden process as it involves the change in the multiplicity. This transition (S1 → T1) is known as intersystem crossing (ISC) and is an important event in photochemistry due to its long lifetime (10+3 sce to 1 sec). This transition becomes more efficient where energy gap between S1 and T1 is small. T1 may undergo changes in the following way. v) T1 may drop to S0 by emission of photon. This process is known as phosphorescence and has a life time of 103-10 sec. vi) it may return to S0 by radiationless decay. or (c) it may start the reaction.

175

All the transitions discussed above may be shown by the modified Jablonski’s diagram as shown above. Energy transfer and photosensitizer Energy transfer process is a secondary method of introducing excitation energy to reacting molecules which are in general, inactive towards direct absorption of light. This process involves the one step radiationless transfer of excitation energy from an electronically excited molecule (Doner) to the ground state of another molecule usually termed as acceptor and is generally used for producing triplet excited state. As the lifetime of singlet states (S1) is very short compared to that of triplet states (T1) the probability of transfer of energy through triplet triplet state is high. Under normal condition, the triplet energy transfer requires the triplet energy, of at least 3 Kcal/mole or more than that of triplet energy of the acceptor molecule. When this condition is satisfied triplet energy transfer takes place at every collision between the triplet excited donor molecule and ground state acceptor molecule. Mechanistically, the donor molecule is excited from S0 to S1 and subsequently converted to T1. The collision of T1 donor with ground state acceptor produces T1 acceptor and ground state donor i.e. D⎯⎯→h1 D D = Donor D1⎯⎯→ ISC D 3 A = acceptor 33Energy A+ D ⎯⎯⎯→transfer + D A = A acceptor A31⎯⎯→ products(sensitisation) D = singlet donor

D33⎯⎯→ Products(quenching) D = triplet donor A3 = triplet acceptor The above process of transfer of energy may be considered as a process of photosensitisation. The donor may be regarded as a photosensitiser. The photosensitiser must have the following characteristic features. (i) It must be excited by irradiation. (ii) It should be present in sufficient quantity. (iii) It must enable to transfer energy to the desired acceptor. A most widely used sensitiser is benzophenone. It has triplet energy 69 Kcal/mole and can transfer energy to acceptor, naphthalene. Thus,

176

Thus photochemical reaction can be carried out with a molecule which can not be excited by direct absorption of light with the help of photosensitiser. It may be mentioned in this context that when triplet excited donor (D3) is converted to products the process is termed as quenching and A is called quencher. Quantum yield Quantum yield or quantum efficiency is the measure of efficiency of a photochemical reaction. It is defined as No.of molecules reacting or formed in unit time Quantum yield( Q) = No.of quanta of radiation absorbedin unit time Its value ranges from zero to one and can be measured by actinometer. Quantum yield differs from yield in chemical reactions. The yield of chemical reaction is usually defined as the number of moles of product formed from one mole of the starting material. Photochemical Reactions – Characteristics Based on the principles presented in earlier sections it may be concluded that photochemical reactions may be either unimolecular or bimolecular in nature. In a unimolecular reaction an electronically excited state decays chemically without involving other molecules. Two common forms of unimolecular decay are known, viz., (i) photolysis in which molecule undergoes cleavage to form smaller parts such as ions or free radicals and (ii) molecular rearrangements. A unimolecular reaction of an excited state is essentially a non radiative decay process. In a bimolecular photoreaction an excited state usually reacts with a second molecule in its ground state. The second partner in the bimolecular photoreaction may be an unexcited form of reactive species or may be some other constituent.

177

Photo-reduction The excited triplet states of carbonyl compounds abstract hydrogen atom from the reacting substrate and forms free radicals which then undergo coupling and disproportionation to yield the products. Photo-reduction of benzophenone may be cited as an example. This reduction has been extensively studied. Normally this reduction is carried out by taking the solution of benzophenone in isopropyl alcohol and irradiating with a radiation of 345 nm. Isopropyl alcohol is inert at this radiation but n→* transition occurs in benzophenone. S1 state of benzophenone drops to T1 which abstracts hydrogen atom from isopropyl alcohol as indicated below to form ketyl radicals.

It may be mentioned that the hydrogen abstration reaction takes place smoothly in the n→* state of ketones than in the →* state. For this reason Michler’s ketone does not undergo photo-reduction on irradiation in isopropanol because conjugation of lone pair of electrons on nitrogen atom with the aromatic ring lowers the energy required for →* transition and →* transition occurs more easily than n→* transition.

178

Photolytic reactions of carbonyl compounds Norrish type I cleavage

(i) at room temperature two acetyl free radicals combine to form diacetyl.

(ii) at temperature above 100, the rate of loss of carbon monoxide becomes very fast and every acetone molecule decomposes to methyl radical.

(b) In the case of unsymmetrical carbonyls, generally that -bond undergoes cleavage which form relatively stable free radicals. Thus,

179

(iii) Suitably placed double bond or cyclopropane ring favours -cleavage.

(iv) Another interesting example is the photolysis of 3,5-cycloheptadienone.

(v) One more interesting example is

180

Norrish type II cleavage Ketones in n→* excited states, either singlet or triplet frequently undergo hydrogen transfer from a -carbon yielding 1,4-biradical. Ketones with low-lying →* states normally do not undergo such -hydrogen transfer. The biradical so formed may (i) revert to original ketone, (ii) form substituted butanol or (iii) can form olefin and enol of a ketone. The last process i.e. formation of olefin and enol of a ketone is known as Norrish type II cleavage traction. Thus,

Sometimes the product obtained correspond to Norrish type I and Norrish type II. Thus,

Photo-addition reaction Most of the photo-addition reaction is associated with the 1,1, adduct. The most excellent example of 1,1, photo-addition reaction is Paterno-Buchi reaction.

181

This reaction involves the addition of an excited ketone to an olefin forming an oxetane. Only ketones with low-lying n→* states react in this reaction. Thus,

Mechanistically radical-like oxygen atom of n→* ketone adds to olefin to form stable biradical intermediate which subsequently form the stable product.

An essential condition of Paterno-Buchi reaction is that the triplet energy of alkene must be either comparable or higher than that of carbonyl compound. If such condition is not satisfied the product will be a dimer of olefin instead of oxetane. Thus reaction of acctophenone and norbornene yields dimer of norbornene while reaction between benzophenone and norbornene affords oxetane.

182

Alkynes can be used in place of alkene in Paterno-Buchi reaction. Thus initial product may be oxetane but the final product is  unsaturated ketones.

Photochemical reaction of ketone and alkene with electron withdrawing substituents proceeds with the formation of oxetane but the reaction path does not involve biradical intermediate.

183

The addition occurs through nucleophilic addition path where (n, *)1 acts as nucleophile. Photochemistry of alkenes As alkenes have no ‘n’ electrons, they have no n→* excited state and so their photochemical activities are confined only with →* states. In alkenes, primarily singlet excited states are involved since intersystem crossing from S1 to T1 is negligible in many alkenes. (a) The frequently encountered photochemical transformation of alkenes involving

T1 states is the cis-trans isomerisation. Since * orbital is antibonding, the energy of the system may be reduced by twisting approximately 90 about carbon-carbon bond as a result of which distiction between cis and trans is lost and the twisted triplet state can return to either cis or trans alkene ground state. Twisting is also favourable in S1 and thus isomerisation can take place through singlet or triplet species. A few examples of cis-trans isomerisation are cited in the next page.

Many photoisomerism is carried out in presence of photosensitisers. Photoisomerism of stilbene in presence of benzophenone as sensitiser has been assumed to take place as indicated below.

184

Both the triplet states undergoes rotation around carbon-carbon single bond resulting in the isomerisation, i.e.

(b) Alkenes can also undergo photochemical dimerisation. The dimerisation takes place by the reaction of triplet alkene with ground state alkene. Thus,

185

(d) Conjugated alkenes: Photochemistry of conjugated alkenes is very much similar to conjugated ketones. 1,3-Butadiene, the simplest member of this family exists in solution as an equilibrium mixture of transoid and cisoid in the ratio 20:1, In excited states these two forms also exist. It has been assumed that the energies of cisoid S1 is much below that of transoid S1. Normally intersystem crossing does not occur. Thus when irradiated 1,3-butadiene undergoes changes through S1 state the products of such irradiation are cyclobutene and bicyclobutane. The proportion of these products depend upon the nature of the solvent used. Reaction occurs only in solution but not in vapour phase. Thus,

This reaction may by explained as

Irradiation of 1,3-butadiene is frequently encountered in organic compounds. Thus,

186

When concentrated solution is used dimerisation occurs. Thus,

The photochemistry of terpene, myrcene, provides an important example of photochemical reaction of 1,3-butadiene system.

Photochemistry of aromatic compounds Aromatic compounds undergo many photochemical transformations. The photochemical rearrangement of simple benzene derivatives provide direct routes to several highly strained molecules. Ex.: Irradiation of benzene gives benzvalene and fulvene. Fourthermore, alkyl benzenes undergo photochemical isomerization to other isomeric alkyl benzene.

187

Fourthmore, alkyl benzenes undergo photochemical isomerization to other isomeric alkyl benzene. Benzene derivatives also add to olefins and dienes. The addition to simple olefin involves rearrangement as well as addition. In the addition to the butadiene, there is a reason to believe that the double bond in that molecule derived from butadiene.

Barton reaction In the Barton reaction, a methyl group in the -position to an OH group is converted into an oxime group. This reaction provides an excellent synthetic route for the conversion of 18-methyl group to 18-substituted steroids. In a synthetic example, 3-acetoxy-5-pregnan-20-ol is converted to the oxime derivative.

Mechanism The alcohol on reaction with nitrosyl choride (NOCl) is first converted to the nitrite, which on photolysis undergoes homolytic cleavage to give alkoxy radical. Abstraction of hydrogen atom from a carbon atom in a -position to the

188

original hydroxyl group produces nitroso alcohol, which tautomerizes to the oxime. The transfer of hydrogen to alkoxy free radical takes place via a six- member transition state. Further, the oxime group can be hydrolyzed to aldehyde. Thus, in Barton reaction, methyl group -position to an OH group is converted into aldehyde functionality.

Applications Corticosterone acetate (1) on treatment with NOCl in dry pyridine gives corticosterone acetate-11-nitrite (2), which on irradiation in toluene gives aldosterone acetate oxime.

Another application of Barton reaction is given below.

Some important reactions in photochemistry In photochemical reaction, 1,2 addition to benzene ring takes place by the n-* excitation of malic anhydride. This is followed by a spontaneous 1,4 addition of Diel’s Alder type to the 1,3 diene. A strained cyclobutene ring formed undergoes a spontaneous eletrocyclic ring opening.

189

Photo oxidation are two types i. Formation of peroxy-compounds which inturn give ketone ii. Oxidative coupling of aromatic compounds. Oxidation of a secondary alcohol to give a hydroxy peroxide with benzophenone as the sensitizer. Alcohol is oxidised in presence of oxygen and sensitizer goes to triplet state which react with alcohol to give hydroxy hydro peroxide

190

5.2 Pericyclic Reactions The reactions discussed in different chapters have been shown to proceed through ionic or free radical mechanisms. There remained, however, a small group of apparently unrelated reactions of olefinic compounds that were rather poorly understood and could not be explained by either of these mechanisms. The following characteristic features of these reactions were of great concern to the organic chemists. 1. The reactions are insensitive towards solvents, catalysts, radical initiators or inhibitors and effected only under the influence of heat (thermal) or light (photochemical). All attempts to isolate, detect or trap intermediates were unsuccessful. 2. The reactions are stereospecific and the results obtained under thermal and photochemical conditions may be markedly different. 3. The reactions are reversible, though the equilibrium often lies to one side or the other, and proceed through a single concerted path involving cyclic transition state and either side of these reversible reactions may involve one or more components. These reactions, which proceed through cyclic transition state, have been termed pericyclic reactions and these pericyclic reactions generally undergo reversible cyclisation and ring opening in most of the cases.

191

Classification of Pericyclic Reactions On the basis of differences in the overall nature of the reaction and the number of participating molecules as well as from the number of sigma () bonds formed or broken, five sub classes of pericyclic reaction are recognized. These are 1. Cycloaddition: It is an adduct-forming pericyclic reaction (X+Y→X-Y). In this raction, one side of the reversible process has more than one pi () bonded molecule, which undergo cyclisation forming two new sigma () bonds. 2. Electrocyclic Reactions: These are reversible ring closure-ring opening pericyclic reactions with the formation of a new  or  bond. Only a single molecule lies on either side of the reversible process. 3. Sigma tropic Rearrangements: Molecular rearrangements in which a  bonded atom or group, flanked by one or more  electron systems, shifts to a new location with the corresponding reorganization of  bonds are sigma tropic rearrangements. 4. Cheletropic Reaction: Addition of a single atomic species to an olefin giving rise to a cyclic compound is known as cheletropic reaction 5. Group Transfer Reaction: As the name implied, in this type of pericyclic reactions an atom or a group is transferred from one centre to another. Phase and Symmetry of Orbitals The two phases of 2p atomic orbital, which has one nodal plane, may thus be conveniently shown either by marking the two lobes with (+) and (-) signs or by shading either of the lobes, say (+) lobe, by black colour.

Molecular orbitals are obtained by linear combination of atomic orbitals (LCAO) and the question of phase obviously arises. Linear combination of two p atomic orbitals in ethene (CH2 = CH2) gives rise to two molecular orbitals ( and *).

192

Molecular orbital has been found to possess two types of symmetries; mirror plane (m) symmetry and two-fold axis of symmetry (C2 symmetry). The following MO has mirror plane symmetry but no C2 symmetry.

Again the following molecular orbital has no mirror plane symmetry but possesses C2 symmetry.

Symmetry Elements of Sigma () Orbital

193

The sigma bond formation in carbon compounds normally involves co- axial overlapping of sp3, sp2 and sp hybrid orbitals. Among these, simplest sigma bond, as is observes in saturated carbon compounds, is formed by of sp3 orbitals. Due to greater contribution of ‘p’ orbital in the hybridisation and for the sake of simplicity, the character of ‘p’ orbital has been given importance in determining symmetry properties of sigma orbital. It has, therefore, been assumed that co-axial overlapping of two ‘p’ orbitals takes place during sigma bond formation. During such overlapping two molecular orbitals-one bonding () and one anti-bonding (*)-are formed.

Obritals Mirror plane (m) C2  Symmetric (S) Symmetric (S) * Anti-symmetric (A) Anti-symmetric (A)

An inspection of the above orbital picture clearly reveals that  orbital is symmetric both in respect of mirror plane and C2 axis of axis of symmetry, while * orbital is anti-symmetric. Symmetry Properties of pi () Orbitals Symmetry properties of  orbitals are determined on the basis of number of nodes present in a particular molecular orbital of a linearly conjugated 

194

system. This will be apparent from the molecular orbital diagrams and their wave representations shown below.

195

In a linearly conjugated p system, the wave function, u, will have n-1 nodes. It will be found that a molecular orbital (u) will be symmetric with respect to mirror plane and anti-symmetric with respect to C2 axis when (n-1) is zero or even number. If (n-1) is odd, the molecular orbital is anti-symmetric with respcet to mirror plane and symmetric with respect to C2 axis as tabulated below. Molecular Nodes (n-1) Mirror plane C2

(n) Zero or even S A Odd A S

Different Approaches to Interpretation of Pericyclic Reactions Since the initiation of investigation by Woodward and Hoffmann for the application of orbital symmetry analyses to pericyclic reactions, there main approaches have so far been developed and these are (i) Correlation diagram method, (ii) Frontier orbital method and (iii) Mobrius-Hückel method.

196

Historically, the first approach was due to Woodard and Hoffmann according to which the symmetry properties of the involved molecular orbitals of the reactants and products are correlated in a diagram, known as Correlation diagram. On the basis of such correlated in a diagram, a set of rules, known as Selection rules, were formulated for different pericyclic reactions. According to these rules, reaction paths of some concerted reactions were described as symmetry-allowed, while some others as symmetry-forbidden. The second approach and perhaps the most popular approach is the Frontier molecular orbital (F.M.O.) approach, developed by Woodward and Fukui and this is popularly known as HOMO-LUMO method. According to this approach, the symmetry properties of only Highest energy Occupied Molecular Orbital (HOMO) and Lowest energy Unoccupied Molecular Orbital (LUMO) are the guiding factors for the interpretation of these concerted reactions. Frontier Molecular Orbital Approach Arrangement of molecular otbitals in order of increasing energy permits separation of antibonding orbitals from the bonding ones by a line, which may be regarded as the Frontier. According to Frontier Orbital Approach, a pericyclic reaction is considered ‘allowed’, if the HOMO of one reactant and the LUMO of the other possess the same symmetry properties. This may be illustrated by cycloaddition of 1,3- butadiane and ethylene to give cyclohexene, a 2s + 4s cycloaddition. Cycloaddition reactions Cycloaddition reactions are concerted and sterespecific. These reactions can be either thermal or photo induced but not both. In these reactions two unsaturated molecules undergo addition to give a cyclic product. Thus, cycloadiation with uv light.

The above cycloaddition reaction of ethene is known as [2+2] cycloaddition reaction and in this case 2-electrons +2 electrons are involved.

197

However, the cycloaddition of butadiene (4-electrons) and ethene (2-electrons) is an example of [4+2] cycloaddition reaction.

A. Frontier orbital theory 9.3.1 [2+2] Cycloadditions As already stated the combination of two molecules of ethene to give cyclobutane is the simplest [2+2] cycloaddition reaction.

In this case, the orbitals of two molecules may overlap in two ways (Fig. 14). When the bond is formed between the two reactant molecules on the same side of the -orbital, the addition is known as superafacial. However, it is known as antarafacial if the bond is formed from the opposite side of the -orbital.

[2+2] Cycloaddition reaction takes place only photochemically but not thermally. According to frontier orbital theory, the cycloaddition can be explained by assuming that the flow of electrons takes place from the HOMO of one molecule to LUMO of the other molecule. Thus, the HOMO of one molecule must overlap withthe LUMO of the other molecule. According to FMO theory, a pericyclic reaction is allowed when the HOMO of one reactant has the same symmetry as the LUMO of the other.

198

We known that ethene has two -molecular orbitals  and * with wave functions, 1 and 2, respectively. In its ground state, , bonding orbital, is HOMO while *, antibonding orbital, is LUMO. (Fig. 15).

Under thermal conditions, when ethene is heated, the -electrons are not promoted and remain in the ground state. This is amply clear by examining the HOMO of ethene moleculed and LUMO of another ethene molecule. This explains that there is no reaction under thermal conditions. Thus, this reaction is symmetry forbidden, see Fig. 16.

The photochemical suprafacial mode of cycloaddition is symmetry- allowed. This is because irradiation of ethene promotes an electron to the antibonding orbital, * ( ⎯⎯→hv * ) , which now becomes HOMO. Since, the symmetry of HOMO (*) of one ehene corresponds with LUMO (*) of another ethene molecule, therefore, the eycloaddition is photochemically allowed, see Fig. 17.

199

Anothor example of [2 + 2] cycloaddition reaction is shown below.

[4+2] Cycloaddtions The most well known Diels-Alder reaction is the thermal [4+2] cycloaddition reaction. It proceeds stereospecifically and smoothly. In Diels-Alder reaction the diene must have an cisoid conformation. Thus, cisoid butadiene adds on to ethene in a cis or syn manner to give cyclohexene.

In cisoid-butadiene, cisoid refers to the geometry around the single bond, which determines the conformation. The two conformations of 1,3-butadiene are:

As already stated, the [4+2] cycloaddition of 1,3-butadiene is thermally allowed; such addition is not possible photochemically. Let us examine the

200

HOMO-LUMO interactions of the p-orbitals which is responsible for forming a new sigma bond in [4+2] cycloaddition. In the thermally included cycloaddition between 1,3-butadiene and ethene, one can visualise the -electrons folowing from HOMO, 2, of the diene to LUMO, 2, of the dienophile (ethene). This reaction is therefore symmetrically allowed but photochemically not allowed.

B. Correlation diagrams Cycloaddition reactions can also be explained using correlation diagrams. This is a theoretical device, developed by Woodward and Hoffmann to interpret pericyclic reactions. According to orbital symmetry theory the symmetry of the orbitals of the reactants must be conserved as they are transformed into the orbitals of the product.

201

Consider a simple example of cycloaddition reaction of two molecules of ethene to form cyclobutane

Let us classify all the molecular orbital of reactants and the products as symmetric (S) or anti-symmetric (A) with respect to symmetry plane. In a [2+2] cycloaddition reaction of the ethene molecules to form cyclobutane, it is assumed that ethene molecules attack each other in parallel planes (i.e., vertically). There are two symmetry planes (the mirror planes), one bisecting the -system of the molecules (plane 1, vertical and other between the interacting molecules (plane 2, horizontal) as shown in Fig. 20.

There are two -orbitals of each ethene molecule,  and * (bonding and antibonding, respectively). The ethene orbitals can interact with another ethene orbitals in four ways to give four -orbitals i.e. 1, 2, 3 and 4. The following figure shows the possible interactions of the orbitals of the two ethene with respect to two symmetry planes (1 and 2).

202

Let us consider the -orbitals of the cyclobutane (product) and analyse them with respect to same planes used for the ethene interaction.

After discussing symmetry properties of the orbitals of ethene and cyclobutane a correlation diagram can be constructed for the ethene-cyclobutane conversion, as shown in the figure. This is the central postulate of orbital symmetry theory orbitals in the reactants must transform into product orbitals that * have the same symmetry. Since the 1 orbital in the product is a high energy orbital, there must be a high activation energy for the formation of the product.

203

The correlation diagram clearly illustrates that [2 +2] cycloaddition reaction is thermally forbidden but photochemically allowed.

Electrocyclic reactions The electrocyclic reactions can take place either thermally or photochemically. Some of the example are:

204

The reverse reaction involving ring opening also proceeds by similar mechanism. The stereochemistry of the formed product is dependent on the whether the reaction is thermal or photo-induced. Thus,

Let us consider electrocyclic cyclisation of 4n systems and [4n+2] systems. Cyclisation of 4 systems The simplest example of a polyene with 4 electrons is 1,3-butadiene. It cyclises to give cyclobutene. The cyclisation takes place by the end-to-end overlap of its p-orbitals and is accompanied by rehybridisation of the carbon atoms involved in bond formation. The cyclisation can be either in phase or out of phase with each other as shown in the following figure.

For the cyclisation involving the formation of a new sigma bond, the existing C-C sigma bonds must rotate so that the p-orbital undergo end-to-end overlap; the energy required for rotation comes either by heat or by ultraviolet. The existing C-C sigma bonds can rotate (to bring the p-orbitals in phase for overlap) in two ways. - The two C-C sigma bonds can rotate in the same direction, either clock wise or anticlokwise. The type of rotation is called conrotatory. - The two sigma bonds can rotate in opposite directions. This type of rotation is called disrotatory.

205

The phases of p-orbitals of the starting diene depends on whether the molecule is in the ground state or in the excited state. Thus, 1,3-butadiene on heating cyclises from the ground state. In this case the electrons that are used for sigma bond formation are in the HOMO, 2. For the reaction to take place, only conrotatory motion is necessary. Disrotatory motion would not bring lobes of p-orbitals in phase for overlap.

The photocyclisation takes place in the excited state. In this case HOMO is

3 in which phases of p-orbitals are in phase and so the rotation of C-C sigma bond has to be disrrotatory for a symmetry allowed reaction to occur. Cyclisation of [4n +2] system A trpical example of electrocyclic reaction of [4n+2] system is the cyclisation of 1,3,5-hexatriene to 1,3-cyclohexadiene. The HOMO of 1,3,5-

206

hexatriene in the ground state is 3. The p-orbitals that form sigma bond are in phase and so thermal cyclisation would require disrotatory motion.

However, under photochemical conditions, the electrons are promoted to * 4, which now becomes the HOMO. In this case the p-orbitals are out of phase and so conrotatory motion is required for bond formation.

The correlation diagrams for the conrotatory process shows that there is a good correlation between the bonding orbitals, 1 and 2, of butadiene and  and -orbitals of cyclobutene. Thus the cyclisation of butadiene to cyclobutene or the reverse is thermally allowed and occurs by conrotatory process. The reaction proceeds with conservation of orbital symmetry. The photochemical conrotatory process in this case will be symmetry-forbidden.

207

Let us consider a disrotatory cyclisation of butadiene in which a mirror plane symmetry (m) is maintained. Irradiation of butadiene (photochemical reaction) promotes electrons from the ground state to the excited state (2 →3).

In this case 1, 2 and 3 orbitals of butadiene correlates with ,  and *-orbitals of cyclobutene. Thus, the first excited state of reactant correlates with the first excited state of product. Hence disrotatory ring-cyclisation of butadiene to cyclobutene and reverse reaction is photochemically a symmetry allowed reaction. However, ground state orbitals of reactant does not correlates with ground state orbitals of product. Thus, thermally disrotatory process is symmetry-forbidden.

After studying the correlation diagrams for both conrotatory and disrotatory processes, it is concluded that the interconversion of butadiene to cyclobutene thermally proceeds in a conrotatory way while photochemically proceeds in a disrotatory way. Working on similar lines, one can draw correlation diagrams for [4n+2] - electrons systems. A example of [4n+2] -electrons system is interconversion of hexatriene to cyclohexadiene. It is concluded from correlation diagrams that the interconversion of hexatriene to cyclohexadiene in a disrotatory mode is thermally

208

allowed (Fig. 35). Whereas, photochemically, the above reaction occurs in a conrotatory mode. In the disrotatory process, m symmetry is maintained. The correlation diagram for disrotatory process clearly indicates that the bonding orbitals of reactant correlates with the bonding orbitals of products  1,,,,  2  3 ⎯⎯⎯⎯→disrotatory 2 Hexatriene Cyclohexadiene Thus, this process is thermally allowed. On the other hand in a conrotatory process c2 axis of symmetry is maintained. The correlation diagram for this process indicates that this process is thermally not allowed as bonding orbitals (in ground state) of hexatriene do not correlate with bonding orbitals (in ground state) of cyclohexadiene

⎯⎯⎯⎯→1232,,,,   Hexatriene Conrotatory Cyclohexadiene  However on irradiation (i.e., photochemically) an electron is promoted from 3 to 4 in hexatriene. Now all the orbitals

209

of hexatrene (in excited state) correlates with orbitals (in excited state) of cyclohexadiene. Thus, conrotatory process for this reaction is photochemically allowed. hv ⎯⎯⎯⎯→1234123,,,,,& conrotatory  Thus, Woodward and Hoffmann selection rules for electrocyclic reactions of 4n and [4n+2] -electrons system is summed up in the form of table-2.

Sigmatropic Rearrangement It is another group of pericyclic reaction. In this rearrangement a sigma bonded atom or a group at the allylic position of a -bonded system migrates to the terminal of -bond. The -bonded system may be a simple ene or a cojugated polyene. Since in this rearrangement a sigma bonded group or atom is migrated, it is known as sigmatropic rearrangement. In this rearrangement the migration of the

210

group is associated with the shifting of the -bond. Some typical examples that may be cited in this connection are,

Classification Classification of sigmatropic rearrangement is based on two aspects. (a) Nature of migration (b) Stereochemical course of the reaction. (a) Nature of migration : Nature of the migration means range of tranfer i.e., from what position the allylic group (the group at allylic position) migrates to what position of the -bonded system. Normally, the -bonded group has two sides which are indicated by I, I and the position of -framework to which the group is migrated is indicated by J. In some cases only one side may migrate to a particular position say j of the -framework and other end may be connected to migrating group or the nature of the migrating group may be such (like H atom) that there is no question of migration of both ends. This type of migration is expressed as (I, j) shift sigmatropic rearrangemet. In some cases both the sides of the migrating group may migrate to the different positions of the -framework, one side may migrate to position, say, i, while other end may be connected to position, say, j of the -framework. Such type of rearrangement is termed as (i,j) shift sigmatropic rearrangement. Actual classification of sigma tropic rearrangement is based on the summation of (I+J) or (i+j). The nature of the summation may be such that these rearrangements has been grouped into two categories. (i) (I+j) or (i+j) may be expressed as 4n system and (ii) (I+j) or, (i+j) may be represented as (4n+2) system where, n=1,2,3,.... etc in both the cases. (b) Stereochemical aspects: As regard to sterochemical aspect the  bonded migrating group may migrate from the same direction of the -bonded terminal. When migration occurs from the same direction it is termed as suprafacial whlie transfer of  bonded group from the opposite direction of -bonded terminals is known as antarfacial rearrangement.

211

Interpretation The cyclic transition state involves has symmetry properties. Consequently, these rearrangement may be explained in terms of F.M.O. method based on the symetry nature of HOMO of the reacting system. For these purpose it has been imagined that in the initial stage, the  bonded group undergoes homolytic cleavage with the formation of two radicals namely one  radical and other one is -radical. It is these two radicals which ultimately interact to form a rearranged product. It may be pointed out that as the reaction is concerted, the migrating group never becomes detached from the migration origin. So, the migrating group maintains the bonding character both at the origin and at the terminus. In order to maintain such bonding character at both the centers, HOMO of both the raicals (, ) must involve in the formation of the rearrangement product. However, out of two HOMO’s, HOMO of -radical system plays the most imprtant role in predicting the course of the reaction as it is more electron rich. Selection rules On the basis of the above argument Woodward and Hoffmann proposed the following selection rules for sigmatropic rearrangement. (a) For 4n system of sigmatropic rearrangement thermally allowed rearrangement is antarafacial while photochemically allowed rearrangement is suprafacial. (b) For (4n+2) system, just the reverse of the 4n system occurs. These two rule may be tabulated as. System Allowed Forbidden 4n (i) Thermal (antara) (i) Thermal (supra) (ii) Photochemical (supra) (ii) Photo (antara) (4n+2) (i) Thermal (supra) (i) Thermal (antara) (ii) Photochemical (antara) (ii) Photo (supra) [1,3]-Shift, [1,5]-shift

212

Here the allylic radical is pentadienyl radical and its HOMO under thermal condition is 3. In [1,5]-shift thermal H migration is extremely facile. This is because this system has m-symmetry and the orbital picture of 3 clearly indicates that in this case suprafacial H migration is possible. The most common example that may be cited is the rearrangement of monosubstituted cyclopentadiene. The rearrangement is so fast that at room temperature only a singlet for methyl group is observed in PMR spectrum.

213

Cope rearrangement It is (3,3) shift sigmatropic rearrangement. It involves six carbon atoms with two double bonds forming two separate allylic systems as indicated below.

Explanation Since in this rearrangement six carbon atoms are involved, it has been assumed that cyclic transition state of this rearrangement bears a close similarity with cyclohexane. Hence this transition state may exist either in chair from or in boat form of conformation as shown below.

214

Out of these two forms of transition states, chair form is preferable as it is stabler than the boat form. The experimental evidence has also been obtained in favour of chair conforamtion. 3,4-Dimethyl-4,5-hexadiene can exist in racemic or in mesoform. The recemic form when heated at 225 it forms E,E product in 90% yield but E, Z product is formed only in small quantity (10%) while meso form yields exclusively E, Z isomer. The above observations can only be explained if transition state assumes chair like conformation as shown below.

But if transition state assumes boat like conformation, product would have been E, Z in the case of racemic form and E, E or Z, Z for meso isomer as indicated below.

However, there are some instances, where rearrangement takes place through boat like conformation. This is because the structure of the molecule is such that it does not allow the attainment of chair like conformation. Thus,

215

Claisen rearrangement Rearrangement of allyl aryl ethers to o- or p-allylphenols is an example of sigmatropic rearrangement, and known as Claisen rearrangement. The allyl group migrates from oxygen to the ring preferably at ortho-position.

Mechanism Claisen rearrangement is a [3,3]-sigmatropic rearrangement which leads to an intermediate, cyclohexadienone and proceeds via a cyclic transition state. The cyclohexadienone intermediate regains the aromatic nucleus via tautomerisation to yield rearranged products. Thus, Claisen rearrangement is concerted intramolecular rearrangement. This is illustrated by the rearrangement of allyl phenyl ether to o-allyl phenol.

Experiments with 14C labelling showed that the position of the 14C atom in the allyl group is inverted during migration to o-position.

216

Further evidence for this mechanism is that if 2-butenyl is present in a phenyl ether, the product phenol has a methyl branch on the side chain.

If both the o-positions are blocked, p-substituted phenol is obtained via two successive shifts of allyl group. Thus, there is double inversion of the position of the 14C label in the allyl group. For example, 2,6-dimethylally phenyl ether rearranges to 4-allyl-2,6-dimethylphenol.

The allyl group is never detached from the oxygen atom unless it is reattached to the aromatic ring. Application Claisen rearrangement can be illustrated in the following reactions.

217

218

Exercise

1. Explain (i) Jablonski diagram (ii) Characteristics of photoreactions (iii) Norrish Type I and II reactions (iv) Photochemistry of alkenes (v) Photochemistry aromatic compounds (vi) Photoadditions (vii) Barton reaction (viii) PartenoBuchi reaction (ix) Photoreduction (x) Photoxidation 2. Explain frontier molecular orbital approach of electrocylcic reactions with suitable example 3. Give an account of sigmatropic rearrangements 4. Draw correlation diagram for 2+2 cyclo addition reaction and predict the results. 5. How is pericyclic reactions classified? 6. Discuss the orbital symmetry of 1,3-butadiene 7. Explain woodward and hoffmann rules with suitable example for (i) Electrocyclic reaction (ii) Cycloaddition reaction (iii) Sigmatropic rearrangements

219