General Organic Chemistry-Part I 1 General Concepts in Organic Chemistry

(A) Types of Organic Reactions: There six common types of organic reactions for the purpose of a beginner. (a) Substitution (b) Addition (c) Elimination (d) Oxidation (e) Reduction (f) Molecular Rearrangement

Substitution Reactions: One group or atom is substituted by another group or atom. heat/ R H ++ Br R Br HBr 2 light

R Br ++ KOH R OH KBr

In the first example, H atom has been substituted by Br atom, so that an alkane is converted to alkyl bromide. In the second example, a Br atomm is substituted by OH group, so that an alkyl bromide has been converted to an alcohol. Addition Reactions: A double bond or a triple bond in a molecule gets added up with another molecule(addendum). Hence the unsaturation in the molecule is vanished or reduced.

Br Br

CH2 CH2 + Br2 CH2 CH2

Cl

CH CH + HCl CH2 CH

In the first example, an alkene(ethene) adds with a Br2 molecule, each carbon atom joins with one Br atom to give 1,2-dibromoethane. Thus the unsaturation is vanished. In the second example, alkyne(ethyne) adds onto one HCl molecule, one carbon joins with H atom and the other with Cl atom to give ethenyl chloride(vinyl chloride). Thus degree of unsaturation is reduced. Note that other conditions of the reactions are not given here. It is just an introduction. Elimination Reactions: One molecule is eliminated from the organic molecule to increase the degree of unsaturation. A saturated compound gives an alkene and an alkene gives an alkyne. Two groups or atoms leave from the adjacent carbon atoms so as to produce a π bond in between them.In fact, this is called β-elimination. We shall know about other eliminations later.

H Cl KOH(alcholic) CH2 CH2 CH2 CH2 + KCl + H2O

H Cl NaNH CH CH 2 CH CH + NaCl + NH 3 Dr. S. S. Tripathy 2 General Organic Chemistry-Part I In the first example, ethyl chloride undergoes β-elimination in which one carbon loses H atom and the the other loses Cl atom to give ethene. In the second example, same thing happens with vinyl chloride to form a triple bond(ethyne).

Oxidation Reactions:

OH O O + K2Cr2O7/H O CH3 CH2 CH C H CH3 C OH O 3 Ethyl alcohol is first oxidised to ethanal(acetaldehyde) and then to ethanoic acid(acetic acid). So an organic molecule existing in the reduced state can be oxided by an oxidising agent to its oxidised state. Reduction Reactions:

O OH

LiAlH4 CH3 C CH3 + 2 [H] CH3 CH CH3

Propanone is reduced to propan-2-ol by a reducing agent such as LiAlH4. The organic molecule in its oxidised state can be reduced by a suitable reducing agent to its reduced state.

Molecular Rearrangement: These reactions are rare and of not important for beginners like you. An organic molecule can undergo total reshuffling of bonds within itself by the action of heat or light or suitable catalyst to form a new product(isomeric).

heat

3,4-dimethylhexa-1,5-diene octa-2,6-diene By mere heating 3,4-dimethylhexa-1,5-diene we get octa-2,6-diene. This is molecular rearragement. An isomeric product is formed from the reactant by intramolecular reorganisation of bonds.

Types of Bond Cleavages: (a) Homolytic Cleavage(Homolysis): A single bond is broken with a one-electron shift to the respective atoms, so that each atom gets back its own electron. Such cleavage is shown by a fish-hook arrow mark( ). Such a cleavage results two free radicals(species having one one unpaired electron).

XY X + Y Br Br 2 Br

The homolytic cleavage of a X–Y bond in the molecule X–Y results two free radicals. A bromine molecule cleaves to two bromine free radicals. The single dot over the atom represents an unpaired electron(free radical). Heterolytic Cleavage(Heterolysis): When a covalent bond(single bond) is broken with a two-electron shift to the more electronegative atom or group, we get a positive and a negative ion. This is shown by a normal arrow mark( ).

Dr. S. S. Tripathy General Organic Chemistry-Part I 3

XY X + Y The heterolytic cleavage of X–Y bond has resulted X+ and Y– ions. Here Y is taken as the more electronegative atom or group.

(B) Reactants in Organic Reactions (a) Substrate: The main organic compound undergoing chemical change is called the substrate. (b) Reagent: The reactant which is responsible for the chemical change of the substrate is called the reagent. Reagent is mostly an inorganic compound. However, it can also be organic(we shall see later).

CH3 CH2 Br + KCN CH3 CH2 CN + KBr Substrate Reagent Ethyl bromide is the substrate and KCN is the reagent.

(C) Reactive Species from Reagents : 1. Electrophiles 2. Nucleophiles 3. Free Radicals

Electrophiles: (Electron Seeking) These are themselves electron deficient species which seek electrons(–ve charge). These are called Lewis acids. These are of the following types. + + + + + + (a) All positive ions (E ): Cl , NO2 , H , (SO3H) , R ( alkyl carbocations), RCO+(acyl carbocations) etc. We shall discuss about carbocations later.

(b) All electron deficient neutral molecules having incomplete octet: like BF3,

AlCl3, BeCl2, carbenes(to be discussed later).

(c) Neutral molecules having vacant d-orbitals such as PCl5, SF6, IF7, SiCl4 etc.

(d) Acidic oxides such as SO3, CO2, P2O5 etc.

Nucleophiles: (Nucleus Seeking): These carry electron pair and hence seek +ve charge. They are of the following types. – – – – – (a) All negative ions: Cl , CN , Br , OH , CH3COO etc.

(b) Neutral molecules having a lone pair: H2O, NH3, PH3, ROH, R–O–R, RNH2 etc. (c) Akenes, alkynes, benzene and other compounds having multiple bonds. (d) Ambidentate Nucleophile: Such nucleophiles have two alternative donor atoms such as CN–(cyanide: donor atom is C) and NC–(isocyanide: doonor atom is N), similiarly SCN– – – (thiocyanate: donor atom is S) and NCS (isothiocyanate: donor atom is N), NO2 (nitro: donor atom is N) and ONO–(nitrito: donor atom is O) etc. Free Radicals: These are species containing unpaired electrons, formed by homolytic fission of sigma bonds(discussed before) catalysed by light(photolysis) or heat(pyrolysis) or by both.

heat/ Br Br 2 Br heat light HO OH 2 OH

OH + H Br H2O + Br Dr. S. S. Tripathy 4 General Organic Chemistry-Part I In the third case, a hydroxyl free radical takes out a H atom from HBr to produce bromine free radical and water molecule. Free radicals produced from reagents often bring about homolysis in organic substrates to form carbon free radicals(see later). Therefore, they are often called radical initiators. Organic peroxides like benzoyl peroxide(BPO) or di tert-butyl peroxide(DBPO) or azobisisobutyronitrile(AIBN) are excellent radical initiators. On heating, they easily produce primary free radicals which intiate the formation of carbon free radicals.

O O O heat - CO Ph C OOCPh 2 Ph C O 2 Ph phenyl Benzoyl peroxide benzoyloxy radical radical Benzoyl peroxide gives both benzoyloxy and phenyl radicals, latter being a carbon free radical.

CH 3 CH3 CH3 heat CH3 C NNCCH3 2 CH3 C + N2 CN CN CN isobutyronitrile radical AIBN AIBN on heating gives the isobutyronitrile radical, which is carbon free radical can can futher initiate formation of other carbon radicals(we shall see later).

(D) Reactive Intermediates From Organic Substrates: Most reactions proceed via the formation of intermediates from the substrates. These intermediates are highly reactive and react further with active species from reagent to form the product. We discuss below five types of such intermediates.

Carbocations: Positive ion in which charge is lying on carbon atom is called a carbocation( earlier called carboniunum ion). These are of two types. + (a) carbenium ions (trivalent: bonded to three atoms/groups) eg. CH3 (methenium ion or methyl carbocation). Carbon is sp2 hybridised(planar) with a vacant p-orbital.

C (sp2 hybridised)

Types of carbenium ions: 0 + + + 1 (primary) : R–CH2 (CH3 , CH3–CH2 etc.) 0 + + 2 (secondary) : R2CH [ (CH3)2CH ] 0 + + 3 (tertiary) : R3C [ (CH3)3C ] (b) carbonium ions:(penta or hexavalent: bonded to 5 or 6 atoms) eg. + + CH5 (methanium ion, also called hypervalent methenium ion), C2H7 (ethanium ion). These are very uncommon.

H H H C H H Dr. S. S. Tripathy General Organic Chemistry-Part I 5

+ + CH5 is the simplest carbonium ion(methanium ion) in which carbon atom is pentavalent. A CH3 structure is bonded with a H2 molecule with a 2e-3c( two electron three centred) bond. The two hydrogen atoms in the H2 molecule can continuously exchange positions with the three hydrogen + atoms in the CH3 ion. Formation of trivalent carbocations(carbenium ions): Carbocations(carbenium ions) can be formed in many ways, two of which are given below. (i) Heterolytic cleavage of C–Y bond in which is Y is more electronegative atom or group like a halogen atom(–Cl/–Br/–I).

+ - CY C + Y

(ii) Addition of an electrophile(E+) to a C-C double or triple bond.

CH2 CH2 + H CH2 CH3 nucleophile electrophile ethyl carbocation (ethenium ion) Reactions carbocations: (i) Addtion with a Nucleophile: Carbocations are electrophiles and hence react with nucleophiles to form the product.

C + OH COH nucleophile

H H C + O CO H H nucleophile (ii) Eliniation of proton :It can lose a proton from the adjacent carbon atom to form C=C (β-elimination)

H B C C CC + BH

alkene A base (B–) abstracts a proton from the adjacent carbon atom and thus a C=C is formed. (iii) Rearragement of carbocations: We shall know later that the stability of carbocations is in the order 30 > 20 > 10 Carbocations swiftly rearrage to equally stable and more stable carbocation by hydride ion or a carbanion shift from adjacent position. The details will be disucussed later.

H H- shift CH3 CH CH2 CH3 CH CH3 n-propyl carbocation isopropyl carbocation (20) (10) Dr. S. S. Tripathy 6 General Organic Chemistry-Part I

H

CH3 CH CH CH2 CH3 CH3 CH2 CH CH2 CH3 sec-pentyl (2-yl) sec-pentyl(3-yl)

CH3 Me shift CH3 C CH2 CH3 C CH2 CH3

CH3 CH3 10 carbocation 30 carbocation In the first case, a less stable 10 carbocation rearranges to a more stable 20 carbocation. In the second case, a 20 carbocation is rearranged to nearly equally stable another 20 carbocation. These two occured by hydride ion shift from adjacent carbon atom. In the third case, the least stable 10 carbocation rearranges to the most stable 30 carbocation by a Me– ion shift. All these happen very fast with rate constants exceeding 109 s–1. Hence all possible products from the rearranged carbocations are formed, with one often being the major product. Hang on for some more time, till we get back onto a threadbare discussion on this subject again. (iv) Addition onto another organic substrate as electrophile: First formed carbocation can add onto a neutral unsaturated substrate to form another bulkier carbocation. Dimerisation of alkenes or the addition of alcohols to alkenes in presence of mineral acid like H2SO4 are examples. CH CH3 3

CH3 CCH2 + CH3 C CH3 C CH2 C CH3

CH3 CH3 CH3 CH3 Tert-butyl carbocation adds onto isobutene to form a bigger 30 carbocation. Readers to note that we are just introducing the types of reactions that carbocations can have. The details of the processes involving this will be taken up later. Also note that here the carbocation acts as electrophile and alkene as nucleophile.

Stability of carbocations: Any charged species becomes stabilised if the charge is dispersed or delocalised by some internal mechanism. If some electron pushing or donating group( +I /+M groups) remains near the +ve charge of the carbocation, it neutralises the +ve charge to some extent. In other words, the +ve charge is partly dispersed or delocalised. We can put it in another way. If the electron deficient nature(sextet) nature of the carbocation is overcome, then it is a stabilising effect. +I(positive inductive effect) or +R (resonance effect) or +H(hyperconjugation effect) effects stabilise carbocation. All these will be discussed in due course. (a) Stabilisation by +I Effect(Electron pushing Effect): The stability of alkyl carbocations can be explained by this. Note that R–(alkyl group) is a electron pushing(+I) group. More the number of alkyl groups bonded to the sp2 carbon more is the stability of the carbocation. Conversely an electron withdrawing group(–I) group destabilises a carbocation.

CH CH3 3

CH3 C > CH3 CH >>CH3 CH2 CH3

CH3 30 20 10 10 0 Maximum charge delocalisation occurs in 3 carbocation as it has three CH3– groups to push 0 electron towards the +ve charge. In 2 carbocation, there are two CH3– groups, and so electron Dr. S. S. Tripathy General Organic Chemistry-Part I 7 pushing effect is less. In ethyl, there is only one CH3–group and in methyl there is none. We shall discuss the stabilisation of alkyl carbocations by another effect called Hyperconjugation, a little later. But below we shall see an example where the carbocation is destabilised by –I effect(presence of an electron-withdrawing group).

O2NCH2 <

+ + CH CH CH CH2 CH CH2 CH2 CH CH2 2 2 Allyl carbocation is stabilised by resonance (two equivalent RSs). Benzyl carbocation is still more stabilised by more number of nearly equivalent RSs (four nearly equivalent RSs) N.B: The number of Resonance structures(RSs) is equal to the number of conjugating units. In allyl there are two conjugating units ie a π-bond and +ve charge(vacant p-orbital) 30 allyl > 20 allyl > 10 allyl

CH3 CH3

CH2 CH C > CH2 CH CH > CH2 CH CH2 30 allyl 20 allyl 10 allyl CH3 30 and 20 allyl stabilised both by resonance and +I effects(also hyperconjugation to be discussed later).

CH2 CH2 CH2 CH2

+ + + CH2

+ In benzyl carbocation, there are four conjugating units( 3 π-bonds and one +ve charge) and hence it has four RSs. Hence the stability order Benzyl Carbocation > Ally carbocation More the number of benzene rings attached to the carbon bearing +ve charge, more is the number of RSs and hence more is the stability.

> C CH > CH2

In triphenylmethyl carbocation, there are 10 RSs, in diphenyl methyl thereDr. S.are S. 7 Tripathy and in benzyl carbocation there are 4 RSs. 8 General Organic Chemistry-Part I Resonance also makes the acyl carbocation highly stable.

RCO RC O I II Hence acyl carbocations are highly stable. Aromatic carbocations like tropylium ion(cycloheptatrienyl carbocation) is highly stable due to aromatic ring resonance. You will know more about it in Huckel rule of aromaticity later.

H H H H (aromatic carbocation) H H H tropyliium ion Resonance stabilisation by an adjacent hetero atom (small size) like O, N, F will make the carbocation more stable.

CH3 OCH2 CH3 OCH2 III

CH3 OCH2 > CH3 CH2 CH2 Due to the resonance effect, methoxymethyl carbocation is more stable than n-propyl carbocation. (c) Hybridisation of C atom carrying +ve charge : (EN of C atom) More is the % of s-character in the bond, more is the electronegativity of carbon atom. Hence a +ve charge will be less stabilised if it remains on a more electronegative atom.

CH3 CH2 > CH2 CH > CH C Existing Hybridisation sp2 sp pure 's'

(d) Bent-bond Stabilisation: Cyclopropyl methyl carbocations are much more stable than expected of its electron pushing nature. Cyclopropane has bent-bonds (banana bonds) with high angle strain. In cyclopropyl methyl carbocation, the vacant p-orbital of carbocation and the cyclopropane ring lie in one plane. This make very effective overlapping between the empty orbital and the bent-bonds on all sides. This is the the cause of its unusual stability.

C C > CH > CH2 H

For the same reason, more the numbe of cyclopropyl rings attached to sp2- carbon more is the stability. See the above order. Unstable Carbocations: Carbocations at bridgehead in bicyclic compounds, vinyl carbocation, phenyl carbocation, ethynyl carbocations are unstable. In fact, such compounds where a leaving Dr. S. S. Tripathy General Organic Chemistry-Part I 9 group like –X lie in the bridgehead or the sp hybrid carbon does not undergo substitution reactions easily. We shall learn later, that in vinyl chloride, the substutution is difficult because greater bond order of the C–Cl bond due to R-effect.

CH2 CH CH C

Relative Stability Order among Carbocations:

O CH3 CH3  CH C > CH  CH CH CH RC 3 2 2 2  CH3 CH

CH3

 > CH3 CH2 > CH3 > CH2 CH > CH C

Here we have put 30 alkyl ahead of benzyl, which you may find the opposite in many texts. But i do not agree with that. I stick to the above order. Benzyl, allyl and 20-alkyl have comparable stabilities, though we have said before that benzyl is more stable than allyl. Similary vinyl and phenyl have comparable stabilities. These have been determined from the kinetic study of several reactions, most important amont them is the SN1 reactions. So theoretical prediction does not always match with actual stability order. Note that we have not put 20, 30 allyl or 20, 30 benzyl carbocations, in the above order which are more stable than their 10 counterparts. Similarly we have not put cyclopropyl methyl carbocation, which is more stable than even benzyl. Their 20 and 30 counterparts + are still more stable. Aromatic carbocations like tropylium ion(C7H7 ) are as much stable as benzyl. Note that unlike carbanions whose relative stabilites can be known from the measured pKA values of their conjugate acids(carbon acids), stability of carbocations cannot be compared so convincingly from any single data source. Hence the orders your find in different sources do not often match. Do not take these conflicts seriously.

Carbanions: Negative ion in which carbon atom carries a negative charge(a lone pair) is called a carbanion. Formation of carbanion: Heterolytic cleavage of C–H bond :

B CH C + BH

carbanion A base (B–) abstracts a H+ ion from a carbon atom and the electron pair is transferred to carbon atom due to the heterolytic cleavage. Thus a negative ion is formed on the carbon atom. Types according to hybridisation: (a) sp3 hybrid: If three atoms are bonded to the carbon carrying the lone pair, as – 0 – 0 – 0 shown in the above figure. R–CH2 (1 ) ,(CH3)2CH (2 ) ,(CH3)3C (3 ) i.e alkyl carbanions. Like carbocations, we have primary(10), secondary(20) and tertiary(30) carbanions, whose stability order is opposite to carbocations. We shall discuss its reason later. It is pyramidal in shape. The lone pair occupies a hybrid orbital. Dr. S. S. Tripathy 10 General Organic Chemistry-Part I

0 0 0 – 3 < 2 < 1 < CH3 (alkyl carbanion stability order)

C

pyramidal (b) sp2 hybrid: If two atoms are bonded to the carbon carrying the lone pair, it is planar in shape. But the p-orbital(unhybridised) takes part in pi-bonding. Phenyl, vinyl carbon are examples of this type.

(phenyl carbanion) CH2 CH (vinyl carbanion)

In all these, the lone pair is present in a hybrid orbital. (c) sp- hybrid: If only one atom is bonded to the carbon atom carrying the lone pair, it will be linear in shape. The lone pair occupies a hybrid orbital. Ethynide or any alkynide ion belongs to this category.

CH C (ethynide carbanion) RC C (alkynide carbanion)

Carbanions are conjugate bases of their Carbon Acids: (BL acid-base concept) A C–H bond can undergo heterolytic cleavage in presence of a strong base and produce its conjugate base, which are nothing but carbanions. Alkanes(R–H), alkenes, alkynes, arenes(aromatic hydrocarbons), ketones, aldehydes and all other compounds having C–H bonds in their structures are carbon acids which can produce their conjugate bases(carbanions) under specified conditions. Carboxylic acids, alcohols, phenols are not carbon acids as their conjugate bases are not carbanions. They are RCOO–, RO– and PhO– ions respectively.

H O O O B RCHCH RCHCH RCHCH (-BH) Resonance stabilised carbanion α A C–H bond adjacent( ) to a electron withdrawing group like –CHO, –CO–, –CN, –NO2 etc. is more acidic than a C–H bond which has no such group in the α position. This is because the carbanion(conjugate base) is stabilised by resonance. Charge delocalisation by resonance is a powerful stabilising effect, as you know, right from the chapter ‘chemical bond’. Active Methylene Group:

If a CH2 group is flanked between two electron withdrawing groups, then that is called active methylene group. Such H atoms are more acidic than the other C–H discussed before i.e having one electron withdrawing group on adjacent position. β-dikeones, β-keto esters(acetoacetic ester) and malonic ester, cyanoacetic esters are examples of this type. active methylene

O O O RC CH C R CH3 C CH2 COOEt 2 ethyl acetoacetate -diketones

EtOOC CH COOEt 2 NC CH2 COOEt diethyl malonate ethyl cyanoacetate Dr. S. S. Tripathy General Organic Chemistry-Part I 11 The carbanion at the active position is stabilised more by resonance delocalisation on both sides.

O O O O O O

RC CH C R RC CH C R RC CH C R

You know that the acid strength is known from the KA or the pKA data. Less the pKA, more is the acid strength. Excepting strong acids (seven acids discussed in ionic equilibrium chapter) which have –ve pKA values, other organic compounds including non-carbonn acids have mostly

+ve pKA values, that means they are weak acids(exception: sulfonic acids). More stable the conjugate bases(carbanions) produced from them, more is the acid strength and less the pKA value. Also remember that if the acid strength is more, its conjugate base(carbanion) strength is less. So indirectly we can compare the base strengths among the carbanions and hence its stability. Greater the pKA of the carbon acids, greater is the base strengths of the respective carbanions and hence less is their stabilities. Conversely, less the pKA values of carbon acids, less is the base strengths of their carbanions, but more is their stabilities. Below given the pKA values of few carbon acids in aqueous solvents. Note that this data will be different if taken in

DMSO(an polar aprotic solvent). Values of H2O and CH3COOH, which are non-carbon acids, are given only for comparision. Carbon acids:

Name pKA Name pKA (aq.) (aq.)

(CH3)3CH53

CH3CH2CH3 51 CH3-CN 25

CH2=CH2 44 CH3COOEt 25

CH4 48 CH3COCH2COCH3 9

CH3–CH3 50

cyclopropane 46 CH3CH2-CO-Et 19-20

CH2=CHCH3 43 CH3–COO-t-Bu 24.5

PhH 43 CH3COCH2COOEt 11

PhCH3 41 Ph-SO2-CH3 29

H2 36

Ph2CH2 33.5

Ph3CH 31.5 CH CH 24

Ph CCH 23 Cyclopentadiene 15

H2O 15.7

CH3COOH 4.74

Analysis:

Acid Strength: CH3COCH2COCH3 > CH3COCH2COOEt > CH CH > Ph3H > Ph2CH2

> PhCH3 > PhH > CH4 > CH2=CH2

You find in the table that pKA values are increasing in the above order, hence acid strength is decreasing. Stabilities of their conjugate bases(carbanions) are in the same decreasing order. However the base strength of these carbanions are in reverse order.

Dr. S. S. Tripathy 12 General Organic Chemistry-Part I Carbanion Stability:

O O O O

CH3 C CH C CH3 > CH3 C CH C OEt > CH C > Ph3C > Ph2CH (I) (II) (III) (IV) (V)

> PhCH2 >>Ph CH3 >CH2 CH (VI) (VII) (VIII) (IX) You can now locate the reason of the stability carbanions (I), (II), (IV), (V) and (VI). These carbanions are stabilised by resonance. Note that more stable a base is, less is its base strength. – – Ph3C is more stable than Ph2CH as the former has more number of resonance structures. Hence – – Ph3C is a weaker BL base than Ph2CH . Base strength of the above carbanions follow reverse order. Vinly carbanion(IX) is most basic while carbanion (I) is least basic. General Discussion on Stability of Carbanions: (a) Resonance Stabilisation: Greater the resonance delocalisation of –ve charge, greater is the stability of carbanions. Allyl and benzyl carbanions are stabilised by resonace, the latter to a greater degree.

- - CH2 CH CH2 CH2 CH CH2 CH2 CH CH2

CH2 CH2 CH2 CH2

- - - CH2 -

Aromatic carbanions like cyclopentadienyl carbanion is highly stable due to aromatic ring resonance. You will study more about this in Huckel Rule of aromaticity later. But can you write the three RSs of this by using arrow marks ?

(aromatic carbanion) cyclopentadienyl carbanion In all these(allyl, benzyl, cyclopentadienyl ion), we have to consider the carbon bearing the lone pair(–ve charge) is sp2 hybridised in stead of sp3. We cannot apply here VSEPR theory and merely count the Steric Number(SN) to predict hybridisation. Here hybridisation is changed to meet the necessity. Here one of the unhybridised p- orbital(say pz) carries the lone pair to be part of the conjgated system(lateral overlap of paralle p-orbitals is possible).

Dr. S. S. Tripathy General Organic Chemistry-Part I 13 (b) Stabilisation by Inductive Effect: –I effect: The presence of an electron withdrawing or –I group delocalises or disperses the –ve charge through sigma bonds. Conversely, the presence of a +I group(electron pushing group) destabilises a carbanion by localising the –ve charge in stead of its dispersal.

O2NCH2 > Cl CH2 > CH3 In contrast to stability of carbocations, nitromethyl carbanion is most stable due to maximum charge dolocalisation of –ve charge by the greater –I effect of NO2– group. Both chloromethyl and nitromethyl carbanions are more stable than methyl carbanion. +I Effect: Relative stability of alkyl carbanions:

CH3 CH3

CH3 > CH3 CH2 > CH3 CH > CH3 C

CH3 10 10 20 30 0 3 carbanion is least stable as the +I effect is maximum(due to three CH3- group) while methyl carbanion is least unstable(most stable) as there is no such +I effect to destabilise it. (c) Hybridisation of Carbon: Greater the s-character of the carbanionic carbon, greater is its electronegavity and hence greater is the –I effect. The –ve charge will be more stable if it will lie on a more electronegative atom. Hence the stability order decreases in the order sp > sp2 > sp3

CH C > CH2 CH > CH3 CH2 sp sp2 sp3 Cyanide ion(CN–) also is highly stable carbanion, as the carbon is sp-hyrbidised and is the conjugate of HCN, which is relatively strong acid than acetylene. All these can be evidenced from the pKA data of carbon acids given before.

HCN CH CH CH2=CH2 CH3–CH3 pKA 9.1 25 44 50 Next to cyanide ion(which is not regarded as a carbanion of organic franternity), ethynyl carbanion is most stable followed by vinyl and ethyl carbanions.

Conclusion: More the stability of the carbanion, less is its base strength and less is the pKA of its conjguate acid(carbon acid). From the pKA table of the carbon acids and from the discussion on stability already made, you can be able fix the stability order for carbanions. Refer always the pKA data of the carbon acids given. That is the real clue to answer the question.

SAQ: Arrange in decreasing order in stability: , , , , Ph– CH C (CH3)3C CH2 CH

Solution: > > Ph– > > CH C CH2 CH (CH3)3C

pKA 15 24 43 44 53 N.B: Cyclopentadienyl carbocation is aromatic like benzene. Dr. S. S. Tripathy 14 General Organic Chemistry-Part I Reactions of Carbanions: Since carbanions are nucleophiles, they react with electrophiles and molecules having electrophilic centres.

C + H CH Electrophile

- O O + C + C CC Electrophilic centre

+ - C + CY CC + Y Electrophilic centre We shall discuss more on reactions of carbanions later. For introduction, it is enough.

Carbon Free Radicals: These are formed by the photolysis(catalysed by uv/visible light), pyrolysis(catalysed by heat) or inititated by other primary radical intiators. This takes place by the homolysis of C–H, C–C, C–Br, C–Cl, C–I or C–O bonds. A few examples are given below. Free radicals can also be formed by the addition of primary free radicals onto C-C multiple bonds.

R H + Br R + HBr (initiated by Bromine free radical)

O h (intiated by uv light: photolysis) CH3 C CH3 CO + 2 CH3

Br (initiated by primary free radicals) RCHCH2 + Br RCHCH2 (N.B: For homolytic cleavage of a sigma bond, customarily only one fish-hook arrow mark is shown for a better clarity. The other fish-hook arrow in each case has been dropped to avoid clumsiness in the diagram.) Structure of carbon free radicals: Carbon free radicals mostly are sp2 hybridised having both trigonal planar and pyramidal(sounds strange, but true) shape. The unpaired electron is present in the unhybridised p-orbital, analogous to carbocations. In acyclic structures the pyramidal structure underoges rapid flipping, while in some sterically hindered cycloalkanes, the flipping is frozen. The former catetory showing rapid pyramidal inversion, gives inseparable racemic product(planar radicals are achiral, as such) and the latter give product with separable d/l pair. Bulkier alkyl radical like tert-butyl radical show pyramidal geometry, while small methyl radical show trigonal planar geometry. Radicals with adjacent heteroatom like O, F etc.( CH3 OCH2 ) which can donate electron assume pyramidal geometry.

Dr. S. S. Tripathy General Organic Chemistry-Part I 15

2pz C C C (trigonal planar) pyramidal inversion Stability of Carbon Free Radicals: Since carbon free radicals are electron deficient species. The factors which stabilise the carbocations also hold good here. The factors are (a) Electron pushing groups(+I groups) stabilise the carbon free radicals. Hence the order of stability among alkyl free radicals is : (Inductive or I effects are discussed later)

CH CH3 3 > CH CH CH3 C 3 >>CH3 CH2 CH3

CH3 30 20 10 10 But this can be better explained by Hyperconjugation effect(see later). (b) Resonance stabilises a free radical.

CH2 CH CH2 CH2 CH CH2 Allyl free radical is stabilised by resonance delocalisation. So also benzyl free radical is stabilised more due greater degree of delocalisation.

CH CH CH2 2 2

CH2

benzyl radical > allyl radical > alkyl radicals N.B: Customarily, the hybrid is not shown in this case, as it looks really akward to give δ. i,e fractional unpaired electron at the specified locations. Some authors give the hybrid structure with fractional radical sign. Resonance with a adjacent heteroatom like O, N, F can stabilise a free radical like a carbocation.

CH3 OCH2 CH3 OCH2 III

CH3 OCH2 > CH3 CH2 CH2 That is why, methoxymethyl radical is more stable than n-propyl radical. Resonance with Electron withdrawing Group(–M) group: This is unique to free radicals. Carbocations are destabilised by the presence of any –M group, while free radicals are stabilised. See the resonance. Dr. S. S. Tripathy 16 General Organic Chemistry-Part I

CCO CCO

Note that radical adjacent to a –M group like -CO-, -CHO, -CN etc. get stabilised by resonance,while a +ve charge(carbocation) adjacent to such group are destabilised by the –I effect. Resonace does not operate in such cases. Capto-dative stabilisation: If the radical is flanked between one –M group and a heteroatom(+M group), it will be still more stable due to resonance on either side. That is called capto-dative stabilisation.

NMe2

O CH3 Ph C CH N

CH3 NMe2 (Wruster's salt)

+ In the second case, the resonance opertates between radical centre and =NMe2 at the para position as well as the adjacent –NMe2 group. Wruster’s salt is a radical cation, which is stable.

(c) % of s-character in carbon atom(Electronegativity): Like carbocations, free radicals produced from sp3 hybrid carbon is most stable and that produced from sp hybridised carbon is least stable.

CH3 CH2 > CH2 CH > CH C 3 produced from: sp sp2 sp (d) In a period (electronegativity) With increase in electronegativity, stability of free radical decreases.

CH3 > NH2 > OH > F Electron deficient p-orbital will more destabilised on a more electronegative atom. (e) Down the group increases: This is nothing to do with carbon free radicals.

F < Cl < Br < I As size increases, the unpaired electron is more dispersed(diffused) in a larger size p-orbital to stabilise itself. N.B: The last two points do not speak anything about carbon free radicals. In the previous point, only methyl free radical belongs to the category. We discussed them under general category.

Relative Stabilities of Free Radicals: triphenylmethyl > diphenylmethyl > 30 allyl > benzyl = 20 allyl > allyl > 30 alkyl > 20 alkyl > 10 alkyl > vinyl > phenyl

Dr. S. S. Tripathy General Organic Chemistry-Part I 17 Reactions of Free Radicals: Carbon free radicals are neither electrophiles nor nucleophiles. They are highly reactive intermediates. Their reactions are non-ionic in nature and can be studied by applying Frontier MO approach(not to be discussed here). Most reactions are non-stereospecific that means all possible products will be formed with varying relative abundance. Sometimes a less stable free radicals undergo rearrangement to a more stable free radical by a shift of atoms like halogen. The most common reactions of free radicals, in general, are (a) Substitution (b) addition (c) mutual combination (d) Disproportionation (e) intramolecular rearragement (f) Autooxidation (g) radical polymerisation We shall see a few cases below. (a) Substitution:

H

CH3 CH CH3 + Br CH3 CH CH3 + HBr propane more stable 20 radical Here we showed the substitution of a primary free radical to form a more stable carbon free radicals. (b) Addition of Br radical to alkenes

CH3 B r

CH3 C CH2 + Br CH3 C CH2

isobutene CH3 more stable 30 radical Br radical combines with an unsymmetrical alkene to form a more stable 30 carbon free radical. (c) Combination: Two free radicals can combine by forming a sigma bond between them.

R + R RR R + Br RBr (d) Disproportionation Reaction:

H

CH3 CH2 + CH2 CH2 CH3 CH3 + CH2 CH2 A H radical (H atom) is transferred from one ethyl radical to the other to form an alkane(ethane) and alkene(ethene) molecule. This is called disporoportionation in organic reactions. Carbanions also can undergo disproportionation reaction. We shall see sometime later. We avoid talking about other reactions of radicals. Whenever required, we shall return back to free radicals in future. Distinction between Carbocations and Carbon Free Radicals: 1. Carbocations are sextet and have positive charge. They are hence less stable. Carbon free radicals contains 7 electrons do not carry any charge. They are relatively less unstable. Therefore simple alkyl radicals like methyl, ethyl have existences while such carbocations have not. 2. Both are stabilised by +I and +M groups. Carbocations are destabilised by –I and –M groups while carbon free radicals are stabilised by –M groups. 3. The rearrangement of carbocations is a very common occurence, while free radicals do not undego rearragement readily. Dr. S. S. Tripathy 18 General Organic Chemistry-Part I Stable Living Free Radicals: Some free radicals are so stable that they always remain alive at equilbrium with their resective products. Moses Gomberg, in 1900, in USA prepared triphenyl methyl radical living in equilibrium with the products by reaction of triphenylmethyl chloride(trityl chloride) with silver metal.

C Cl Ag C + AgCl

living radical

Ph3C + CPh3 Ph3CCPh3 The product(hexaphenylethane) remain in equilibrium with 2% of living trityl free radicals. The trityl radical also reacts with oxygen gas to form triphenyl acetic acid as another minor product. We have also discussed about capto-dative stabilisation to make Wruster’s salt stable.

Carbenes: Carbenes are species in which carbon is divalent and carries two non-bonding electrons and is an electron sextet in the valence shell. Types: (a) Singlet Carbene: C- is sp2 hybridised. One of the hybrid orbitals contains a lone pair. it is diamagnetic. One p orbital is empty. It has a bent shape. The bond angle lies between 100 – 1100. Methylene carbene has the BA of 1040.

Triplet Carbene Singlet Carbene

(b) Triplet Carbene: C -is also sp2 hybridised. It is a diradical having two unpaired electrons and hence is paramagnetic. One electron is present in each of a hybrid orbital and the unhybridised p-orbital. It is also bent having greater bond angle than singlet carbene. The bond angle triplet carbene varies between 130 – 1500. Methylene carbene has a BA of 1360.

Relative Stabilities: (1) In general triplet carbene is more stable(Hund’s rule of maximum multiplicity) than singlet state. Note that this is the ground state triplet(as against the usual triplet state in organic photochemistry which is the excited state triplet). Singlet state is less stable than the triplet state by 8 Kcals/mole. This is the case when carbenes are made up of only C and H atoms. Dr. S. S. Tripathy General Organic Chemistry-Part I 19

Examples: H2C (methylene); CH3 CH(methyl methylene carbene);

Ph CH (phenylmethylene); (Ph)2C (diphenylmethylene); HC C C H (propargylene) Since triplet is more stable, it is less reactive and hence more selective. Singlet carbene often transforms to triplet state by transfer of energy to other intert gas molecules like N2, Ar by collision. Hence triplet state is more likely to exist in gaseous state while singlet state is more likely to exist in liquid state(aqueous medium). Both singlet and triplet carbenes undergo reactions but in different manner(discussed later). (2) When there is a heteroatom like N, O, X(halogen) bonded to the sextet carbon, the lower energy state(more stable) is singlet carbene. Triplet carbene is less stable.

Examples: CH3 OCH(methoxymethylene), Cl CH (chloromethylene)

Cl2C (dichloromethylene); Ph C Cl (phenylchloromethylene)

Generation of Carbenes: (1) By photolysis or pyorolysis of diazo compounds: Diazoalkanes are compounds having following RSs.

RCNN RCNN R R

By the action of light or heat it decomposes to form carbene and N2. Carbene further reacts with another reactant to form the product. The 2nd RS is taken to show the decomposition.

h RCNN or heat RC+ N2 R R

Diazomethane (CH2N2) is a very common compound which is used in reactions to generate methylene carbene as shown above. (2) Photolysis or pyrolysis of Ketenes:

R R h RCCO RC+ CO or heat Ketene A ketene loses a CO molecule to give a carbene. (3) α-elimination of trihaloalkanes by a strong base:

Br Br H Br t-BuO K - Br C C C Br (-t-BuOH) Br Br Br Br

Dr. S. S. Tripathy 20 General Organic Chemistry-Part I On treatment with a strong base like t-BuOK, a trihaloalkane gives a dihalocarbenene in two steps as shown above. A H+ ion is eliminated in the first step by the base (t-BuO–) and then a X– is eliminated in the second step. Chloroform gives dichlorocarbene.

Carbenoids: Compounds that react like carbenes but are not true divalent electron deficient species like carbenes are called carbenoids. They react in same manner as carbene does. Zn-Cu CH I ICH Zn I 2 2 ether 2 (Simmon-Smith Reagent) carbenoid

Other carbenoids are RCH(X)Li, RCX2Li etc. They produce singlet carbene during the reaction and the reactions are often stereospecific(see later).

Reactions of Carbenes: (1) Insertion with a σ-bond: Carbene is inserted between a C–H or a C–C bond increasing the MM by 14 units. X-H > C–H > C–C ( X= heteroatom lke O, N, or halogen)

(C–H : 30 > 20 > 10)

H CH3

C + CH2 C

H CH3 CH2N2 CH CH CH CH CH CH + CH CH CH CH 3 3 h 3 2 3 2 2 3 major minor

CH N CH COOH 2 2 CH COOCH 3 h 3 3 The carbene is inserted with the O–H bond most preferentially. (2) Addition to C=C: Singlet carbene reacts with alkene( or alkyne) in one step process via a TS(concerted reaction) to form cyclopropane(cyclopropene) derivative. The reaction is stereospecific. Cis alkene gives Cis-cyclopropane derivative while trans alkene give trans product. This is called cheletropic reaction under the broad head of pericyclic reactions. Here the singlet carbene acts as an electrophile

CH2

H H CH2N2 H H CC h CH CH CH3 3 CH3 3 Cis-1,2-dimethylcyclopropane Cis(Z)-but-2-ene

CH2

H CH 3 CH2N2 H CH3 CC h CH3 H CH3 H Trans-1,2-dimethylcyclopropane Trans(E)-but-2-ene Dr. S. S. Tripathy General Organic Chemistry-Part I 21 Triplet carbene, which itself is a diradical, reacts with alkene in a two-step process with the formation of another intermediate diradical. The intermediate has a chance to undergo rotation about the C–C. Hence it is not a stereospecific reaction. Each of the Cis and Trans but-2-ene gives a mixture of cis and trans 1,2-dimethylcyclopropane. Here the carbene can act as a nucleophile as well as a electrophile. This happens when either Cis or Trans but-2-ene is allowed to react with diazomethane in presence of an inert gas like Ar or N2 in gaseous phase. The singlet carbene transfers energy due to collision with gas molecules and assumes triplet state before reaction.

H H CH3 CH3 Cis CH2 CH2

H H CH2N2 CC H H CH h 3 CH3 (N2 or Ar) CH3 CH3 diradical Cis(Z)-but-2-ene CH 1800 rotation 2

H CH3

CH3 H

H CH3 CH3 H Trans

In the same manner, Trans(E) but-2-ene under an intert atmosphere will also give a mixtrue of both cis and trans 1,2-dimethylcyclopropane.

By using a carbenoid ICH2ZnI(iodomethylzinciodide: called Simmon Smith reagent), we can carry out this reaction, and in this case the reaction will be stereospecific, as explained before. (3) Dimerisation of Carbenes:

Carbenes can undergo mutual combination to form a dimer joined by a C=C.

C + C CC

OCH CH3O OCH3 CH3O 3 C + C C C

CH3O OCH3 CH3O OCH3 Chlorodimethoxymethane on treatment with t-BuOK, produce the dimethoxymethylene carbene by α-elimination of HCl, and the carbene undergoes dimerisation with itself to form tetramethoxyethene.

Dr. S. S. Tripathy 22 General Organic Chemistry-Part I (4) Intramolecular Rearragement: Carbene can undergo intramolecular 1,2- hydride or alkyl or aryl shift to form stable compounds. See these examples.

hydride shift CH2 CH CH2 CH2 ethene H methylmethylene In this case, a hydirde(H–) ion transfer occurs from the adjacent carbon atom consequent upon the migration of lone pair from the sextet carbon to form a pi bond. This is called 1,2- shift.This reaction takes place when diazoethane (CH3CHN2) is subjected to photolysis. Similarly when α-diazo ketone is heated we get rearragned ketene. See below.

O O Ph Ph C Ph Ph- shift C Ph heat C C CO C Ph (benzene) Ph N (ketene) diphenylethenon N (2-diazo-1,2-diphenylethan-1-one) This is called Wolf rearrangement. We shall see numerous reactions of carbenes, important among them is Reimer-Tiemann reaction in phenol which makes use of dichlorocarbene as electrophile to form salicylaldehyde and Arndt-Eistert Synthesis of a higher carboxylic acid(next higher homologue) by reaction of diazo ketone with Ag2O follwed by hydrolysis. This takes place via Wolf rearragement as shown above. The ketene formed is hydrolysed by H2O to form carboxylic acid. We shall see all these in future. Stability of Carbenes: Since carbenes are electron deficient like carbocations and carbon free radicals. electron donating groups can stabilise them. Particularly when a small size hetero atom like F, O, N is adjacent to the carbene, resonance stabilisation does occur.

CH3OC H CH3 OCH

CH3OCH2 and F2C carbenes are highly stable and least reactive.

N.B: Carbenes have been isolated or trapped in the solid state by matrix isolation method in the crystalline matrix of solid xenon.

NITRENES: Nitrenes are nitrogen analogues of carbenes. The species in which N is monovalent and is an electron sextet is called a nitrene. Like carbenes, nitrenes are mostly electrophiles.

N N HN imidogen Singlet Triplet Dr. S. S. Tripathy General Organic Chemistry-Part I 23 Types: (a) Singlet nitrene N-atom is sp2 hybridised. Two lone pairs occupy the two hybrid orbitals. One p-orbital is empty. (b) Triplet nitrene: N-atom is sp hybridised. One lone pair occupies a hybrid orbital. The two unpaired electrons occupy the two unhybridised degenerate p-orbitals. Triplet nitrene is more stable than singlet nitrene.

The simplest nitrene is imidogen(HN) as shown above formed by the photolysis of HN3(hydrazoic acid).

Generation of Nitrenes: (1) Photolysis or pyrolysis alkyl or aryl azides:

RNNN RNNN R = alkyl, aryl or H

h RNNN RN+ N or heat 2 nitrene

Azides on treatment with light or heat loses a molecule of N2 to give a nitrene intermediate. This is similar to the decomposion of diazo compounds to give carbenes. Reactions of nitrenes: (1) Cycloaddition reaction: Like carbenes, singlet nitrene reacts with alkene with high degree of stereospecificity while in presence of inert ga,s triplet nitrene reacts with total loss of stereospecificity.

Et N Et N H H RN H H CC 3 CH3 h CH3 CH3 CH3 Cis- aziridine product (major)

Similarly, trans alkene gives trans aziridine product predominantly. In present of inert gas like

N2 or Ar, a mixture of cis and trans aziridine products is obtained from either cis or trans alkene. Obviously the triplet nitrene(a diradical) reacts in two steps like tripet carbene to give two products. (2) Insertion Reaction: Like carbenes, nitrenes get inserted to C–H bond with more selectivity. 30 > 20 >10

H NH Ph Ph N CH3 C CH3 CH3 C CH3

CH3 CH3

Dr. S. S. Tripathy 24 General Organic Chemistry-Part I Alkyl/Aryl nitrenes form 20 amines when inserted with a C–H bond. Here the major and exclusive product is formed by insertion in a 30 C–H bond.

NH Et EtN CH3 CH2 CH3 CH3 CH CH3 + CH3 CH2 CH2 NH Et (major)

(3) Intramolecular Rearrangement:

LIke carbenes, nitrenes too undergo intramolecular rearrangement with 1,2-shift of alkyl or aryl carbanions to form isocyanates(like ketenes in case of carbenes). This is nitrene analogue of Wolf rearrangement of carbenes. One such case found in Curtius rearrangements, in which acyl azides on heating produces alkyl isocyantes. But recent research has revealed that nitrene is not formed during the thermal decomposition of acyl azide to isocyanate. It is a concerted(one step) reaction in which, the loss of N2 and the 1,2-shift(rearrangement) take place simultaneously. Earlier it was believed that a nitrene is formed as the intermediate before the 1,2-shift(two step process). However, photochemical decomposition of acyl azide goes via nitrene formation. The is proved by the formation appreciable quantity of the unwanted nitrene insertion product with solvent molecule alongwith isocynate. Phtochemical Reaction:

O O h 1,2-shift Ph CNNN Ph CN Ar N C O cyclohexane alky l isocynat

O NH C Ph

N-cyclohexylbenzamide (nitrene insertion product)

In the above photolysis reaction, nitrene is formed which is evidenced by the formation of the nitrene insertion product with cyclohexane solvent. Thermal reaction(Curtius rearrangement):

O heat Ph CNNN RN CO+ N2

In thermal process, one step reaction occurs without formation of nitrenes.

Dr. S. S. Tripathy General Organic Chemistry-Part I 25 (E) Electronic Effects: How the presence of on atom or group influences the whole structure and hence many physical properties such as bond order, bond length, acid/base strength, stability of intermediates and host of others, all these can be explained by electron displacement or delocalisation within the species by the following electronic effects. (a) Inductive or I - Effect (b) Resonance(R)/Mesomeric(M)/Conjugation Effect: (c) Hyperconjugation or H-effect (d) Electromeric or E-effect

The first three are permanent effects in neutral molecules while last one is temporary. Many things you already know, i.e we have discussed on R-effect(in our chemical bond program) and I-effect just before we came onto electronic effects. However, we have not discussed anything about H- and E- effects. In any case, we shall formally and systematically study each effect once again. INDUCTIVE OR I- Effect: I-effect works through sigma bonds over a short distance from the orignal I-group producing the effect. It is a feeble effect as it works through sigma bonds and hence can be dominated by other electronic effects(R or H effect) which are more pronounced than this. Types: (a) +I effect (Electron pushing/donating effect) (b) –I effect (Electron withdrawing effect) I-effect is the pushing and pulling of electron pair in sigma bonds. –I Effect: (Electron Withdrawing Effect) The presence of an electronegative atom or group(X) produces polarity in the C–X bond and this polarity develops a smaller polarity in the adjacent sigma bond and this induction persists upto a few adjacent sigma bonds and thereafter the effect completely vanishes. The group X is called a –I group or a EWG (EWG : electron withdrawing group)

+ + + + - CCCCCX

-I group Few –I groups with their relative order(decreasing order) of electron withdrawing effect is given below.

+ –NR3 > –NO2 > CCH> –CN > –SO3H > –CHO > –CO > –F > –COOH > –COCl > ≥ –CONH2 > –Cl > –Br > –I > –OR > -OH > –NH2 > –C6H5 –CH=CH2 > –H

Relative to H, all others have higher –I effect. The authenticity of this order will be verified when we discuss about the application of the effect. +I Effect (Electron Pushing/Donating Effect):

The group producing +I effect (say Y) will produce a negative pole on the adjacent carbon atom which in turn will induce -ve pole in adjacent carbon atoms with decreasing magnitudes and after a few bonds, it will die out completely. These groups(Y) are called +I groups or EDG (electron donating groups).

+ - - - YCCCC

+I group Dr. S. S. Tripathy 26 General Organic Chemistry-Part I +I groups have lesser electron withdrawing capacity than H atom, hence they, in stead produce electron donating effect. A few +I groups with decreasing order of electron donating effect: –O– > –COO– > –R

Note that –OH group is a –I group but alkoxide ion (–O–) is a +I group. Similarly –COOH is a –I group but –COO–(carboxylate ion) is a +I group. All alkyl groups have lower electron withdrawing power than H atom and hence they are considered as +I groups. Among alkyl group, the +I effect increases with increase in length(upto 3 carbon atoms) and increase in degree of branching. < CH3 < CH3 CH2 CH3 CH2 CH2 = ......

CH3 CH3 CH C >> 3 CH3 CH RCH2 > CH3

CH3 10 10 30 20

Application of I-Effects: Relative Strength of Acids:

(a) Greater the –I effect, greater is the ease of the dissociaton of O–H bond in oxo acids and greater is the acid strength. We can explain in a reverse way too. Greater the –I effect, greater is the stability of the conjugate base of the acid by charge delocalisation. Hence greater is the acid strength. You already know that greater the acid strength, less is the pKA value.

O O

XCH2 C OH XCH2 C O + H (favouring acid dissociation) O

XCH2 C O (conjugate base)

(b) Greater the +I effect, greater the difficulty in the dissociation of O–H bond in acids and hence less the acid strength. The conjugate base is also destabilised by +I effect, hence the acid is of less strength. We can explain in either of the ways.

O O

YCOH YCO + H (disfavouring dissociation) O

YCO (conjugate base) Dr. S. S. Tripathy General Organic Chemistry-Part I 27 Conclusion: –I effect increases acid strength while +I effect reduces acid strength. Examples: 1.

O2N CH2 COOH > NC CH2 COOH > Cl CH2 COOH > CH3 COOH pKA 1.48 2.47 2.87 4.74

Since the –I effect decreases in the order –NO2 > –CN > -Cl, the acid strength also decreases. No such effect is present in acetic acid. Hence all others are stronger than it. 2.

F CH2 COOH > Cl CH2 COOH > Br CH2 COOH >>I CH2 COOH CH3COOH pKA 2.57 2.87 2.90 3.16 4.74 As –I effect decreases among halogen atoms, the acid strength decreases. But all haloacetic acids are stronger than acetic acid, as the latter does not experience –I effect. 3.

Cl Cl

Cl C COOH >>>ClCH COOH ClCH2 COOH CH3COOH Cl 2.87 4.74 pKA0.65 1.25 More the number of halogen atom of a particular type, more is the cumulative –I effect and hence greater is the acid strength. Trichloroacetic acid is the strongest among chloroacetic acids. All of them are stronger than acetic acid. 4.

Cl Cl Cl

CH3 CH2 CH COOH > CH3 CH CH2 COOH > CH2 CH2 CH COOH pKA 2.86 4.05 4.52

> CH3 CH2 CH2 COOH 4.82

As the distance of the –I group decreases w.r.t the –COOH group, its effect increases, and hence acid strength increases. All the chlorobutanoic acids are stronger than butanoic acid as the latter has no –I effect to its credit. 4.

O O O > HCOH CH3 C OH> CH3 CH2 C OH pKA 3.77 4.76 4.88

Dr. S. S. Tripathy 28 General Organic Chemistry-Part I Formic acid is stronger than acetic acid, which in turn, is stronger than propionic acid. After that i.e butanoic acid onwards, the acid strength is more or less same. There is the +I effect of a methyl group(CH3–) in acetic acid, which disfavours the ionisation. There is no such effect in formic acid. In propionic acid, the ethyl group(Et–) group produces more +I effect to further decrease the strength. But longer n-alkyl groups than ethyl have no additional +I effect for which acid strength levels off after propionic acid. Butanoic acid has a pKA of 4.82, pentanoic acid has 4.86 which are more less comparable with propionic acid. The other way to explain this is the relative stabilisation of their conjugate bases(RCOO–). More the +I effect, more is the destabilisation and hence less is the corresponding acid strength. 5.

CH3 COOH > (CH3)2CHCOOH > (CH3)3CCOOH 4.74 4.86 5.3 pKA As the +I effect increases with degree of branching the acid strength decreses. Pivalic acid(2,2- dimethylpropanoic acid) is the weakest.

6.

CH3 CH3

CH3 OH >>CH3 CH2 OH CH3 CH OH > CH3 C OH

CH3 pK 15.5 15.9 A 16.5 18.0

Though alcohols are not acids for general purpose, they have acidic H atoms and are very weak acids having very high pKA values, slightly greater than KA/KD of water(15.7). Hence the acid strength of alchols varies in the order MeOH > other 10 alcohol > 20 alcohol > 30 alcohol In essence, more the digree of branching in alcohol, less is the acid strength. This can be explained in three ways. (a) The order of increasing +I effect between the R-groups from Me– to t-Bu– reduces acid strength. (b) The conjugate bases i.e their alkoxide ions are destablised by greater +I effect. (c) Due greater steric crowding(to be discussed later), the stabilsation of the alkoxide ion due to solvation will be decreased as the degree of branching increases from 10 to 30. This is called Steric Inhibition of Solvation.

(Note that methanol and H2O have nearly same KA values. In fact MeOH has bit lower value. We cannot make any argument on their relative values. Sometimes we are tight leaped while we compare the data. We might question the credibility of data measurement or unable to know the actual cause. It is better to remain silent on such occasions than to cook a reason, which, guys like you, will surely not appreciate) 7. Halo group enhances acid strength in ethanol. See the following.

CH3CH2OH <

Dr. S. S. Tripathy General Organic Chemistry-Part I 29 (c) Hybridisation of C- bonded to acid function: Greater the % of s-character, greater is the –I effect and hence greater is the acid strength.

COOH 2 sp sp sp3 HC C COOH > = CH2 CH COOH > CH3 CH2 COOH 4.9 pKA 1.8 4.2 4.2 propargylic acid acrylic acid propionic acid (propiolic acid) benzoic acid

Prop-2-ynoic acid(propiolic/propargylic acid) is the strongest while propanoic acid is the weakest. Benzoic acid and acrylic acid have same acid strength as both have sp2 hybrid carbon atom bonded to –COOH group. N.B: Benzoic acid is stronger than aliphatic carboxylic acids like acetic acid, propinonic acid and higher acids. because of the above reason.

FORMIC ACID Vs. BENZOIC ACID:

Interestingly benzoic acid(pKA = 4.2) is convincing weaker than formic acid(pKA = 3.77). This can be explained by using R-effect. Let me explain this, lest i might forget. Formic acid does not have any C-atom to link to –COOH function, so +I/–I issues are not to be raised. On the contrary, in benzoic acid there is a permanent –M effect produced by –COOH onto the benzene ring, and hence there is some amount of electron pushing towards the –COOH by the Ph– group although this is countered by the R effect that is inerent between –OH and -CO- parts of COOH. Since in formic acid there is no R– group to complicate, the net result is that the dissociation in benzoic acid is less compared to formic acid. To put it ia another way, phenyl group produces a mild +I effect(due to resonance) on the –COOH group for which dissociation is bit hindered. ( I know, that this explanation is not highly convincing to me even. But somehow we have to rationalise it like this). (d) –I vs. +I Effect: Phenol is more acididc than alochol. Without bringing R-effect for phenol, this can be explained only by using I-effects. In phenol, Ph– group produces –I effect which enhances acid strength, while in alcohols (R–OH), there is +I effect of R– group which reduces the acid strength. -I group +I group

OH >>CH3OH CH3CH2OH

pKA 10 15.5 15.9 Later, we can make use of R-effect to explain the stability of PhO– ion and hence greater acid strength of phenol relative to alchols. Note that ealier i said that Ph-group produces +I effect(in benzoic acid) and now in phenol i said it is producing –I effect. Yes, that was due to resoance and here that si no such resonance. Note also that we cannot explain why phenols are weaker acids than carboxylic acids(RCOOH) by using I-effects. For that we have to use R-effect(to be discussed later). The R-effect in benzoic aicid is different from that in phenol, as they work in opposite diretions. We shall see to it later.

Dr. S. S. Tripathy 30 General Organic Chemistry-Part I Relative Strength of Bases:

Broadly speaking, in the light of BL theory, all negative ions and neutral molecules having a lone pair in their central atoms are bases. But for common purpose, we consider, organic compounds containg N atoms like amines(aliphatic, aromatic) as bases.

Note that more is the stability of the base by electron delocalisation, less is the base strength.

This is known from the lower pKA value of the corresponding conjugate acids. Let us only apply I- effect to explain base strength.

Presence of a +I group near to the lone pair, will make the base less stable and hence more basic. The lone pair is more available for donation. Presence of a –I group near to the lone pair, will make the base more stable due to delocalisation, and hence it will be less basic. The lone pair is less available for donation.

YCH2 NH XCH2 NH2 less stable more stable (lone pair localised (lone pair delocalised (more basic) (less basic) Conclusion: +I effect increases base strength while –I effect decreases the base strength. Examples: 1.

CH3

CH3 NH > CH3 NH2 > NH3 pKA (of conjugate acids) 10.71 10.64 9.26

Alkyl amines are stronger bases than ammonia(NH3), because alkyl group produces +I effect to enhance the availability of lone pair on N atom(reduce its stability). Hence the pKA values of their conjugate acids are greater.

Note that we shall continue to compare the strengths of bases from pKA values of their conjugate bases. Greater the pKA value, greater is the base strength. We could have given their pKB values for comparison. However, we have uniformly used pKA values for comparing relative acid strength(inversely related) and base strengths(directly related).

2.

Cl CH2 NH2 < CH3 NH2 Chloromethyl amine is a weaker base than methyl amine because of –I effect fo Cl atom.

3.

pKA CH3OH << CH3NH2 (of conjugate acids) -1.5 10.64

If we compare an alochol with an amine as bases, then alcohols(derived from H2O) are much weaker bases than amines(derived from NH3). The lone pair on N- atom is less tightly bound to the N- nucleus as it is less electronegative than O-atom. Hence the lone pair is more available.

Dr. S. S. Tripathy General Organic Chemistry-Part I 31 4. – – NH2 >> OH

pKA 38 15.7 (of conjugate acids)

Since as acid NH3 is much weaker (pKA = 38) than H2O (pKA = 15.7), their conjugate bases have opposite strength. Similarly, note that alkoxide ions are stronger bases than their respective alochols and amines, though neutral amines are stronger bases than neutral alcohols.

– CH3O > CH3-NH2 > CH3–OH

pKA 15.5 10.64 –1.5 (of conjugate acids) So in general, the base strength is in the order – RO > R–NH2 > R–OH

Basicity of Aliphatic Amines: (1) Methyl amines:

CH3 CH3

CH3 NH >>CH3 NH2 CH3 N > NH3 CH3 (Aq. Medium) pKA (conjugate acids) 10.73 10.62 9.8 9.26 We can explain this in any one of the following two ways. (a) Steric Hindrance to Electron Donation: Though there is maximum +I effect in trimethyl amine(30 amine), its capacity of donation of electron pair is greatly hindered by high steric crowding of three methyl groups around the lone pair. Just like you are are a billionare, but your home is inaccessible to the needy persons wanting monetary help(here it is H+) from you, as you are living in a highly crowded area. Trimethyl amine loses more due to steric crowding than it gains due to greatest +I effect. The net result is it is third in the list, even weaker than methyl amine. In dimethyl amine(20 amine), the steric crowding due to two methyl groups is not as much severe as in trimethyl amine. Hence it gains much more due to +I effect of two methyl groups than it loses due to steric crowding. Just like you are millionare (not billionare like trimethyl amine), and since your home is not much crowded as there is road for the needy persons to access you, you are known to be the virtual richest man to the public i.e it is most basic among the three. Methyl amine has the minimum +I effect though steric crowding is also the least. Hence its position becomes second. Just like you are man of lakh (lakhpati in Indian language) but highly accessible to needy persons. So you appear richer than billionare(trimethyl amine) but less rich than dimethyl amine.

Note that NH3 is weaker than all the alkyl amines, as the latter is not supported by an +I effect. (b) Steric Inhibition to Solvation of Conjugate acids: More the stability of the conjugate acids of these amines, more is the base strength of bases. The conjugate acids (ammonium ions) of the three amines and NH3 are shown below.

CH3 CH3

CH3 NH CH3 NH2 CH3 NH3 NH4 CH3 Dr. S. S. Tripathy 32 General Organic Chemistry-Part I These ions are stabilised both by +I effect of Me– groups and by hydration(solvation) of the ion by water molecules through ion-dipole inertaction(H-bonding). Due to greatest steric crowding in trimethyl ammonium ion, the hydration is minimum. This is called Steric Inhibition to Solvation(SIS). Trimethyl amine loses more due to SIS than it gains by the +I effect of three Me– groups. Hence it becomes least basic among the methyl amines. Dimethyl amine gains more due to +I effect than it loses by SIS. Hence it is the most basic. Thus + methyl amine is left out to occupy the 2nd position. NH4 ion does not gain anything from +I effect. So it is least basic even though SIS is minimum. Gas phase base strength: In gas phase, steric crowding is not an issue as there is enough empty space in gas. Also since there is no solvent to stabilise the conjugate acids, the order follows only from the + I effect for all amines. 0 0 0 3 amine > 2 amine > 1 amine > NH3 IMP: If no mention of any phase is there in any question, you presume the base as well as acid strengths are to be analysed in aqueous medium.

(2) Ethyl amines: The replacement of Et- group in place of Me- group makes the following change in the order.

Et Et

Et NH >>Et N Et NH2 >NH3 Et pKA (conjugate acids) 11.09 10.8 10.7 9.26 In this case, diethyl amine is most basic followed by triethyl amine and least basic is ethyl amine. Here the gain due to +I effect in 30 amine compensates the loss due to steric crowding so as to slightly exceeding the basicity of ethyl amine.

Note that EtNH2 has nearly the same basicity as Me3N. (3) Isopropyl amines:

iPr iPr

iPr N >>iPr NH2 iPr NH >NH3 iPr pKA (conjugate acids) 10.75 10.63 10.57 9.26 In this case 30 amine is most basic and 20 amine is least. But triisopropyl amine has nearly same 0 basicity as EtNH2. If you compare between isopropyl amine and ethyl amine(both 1 amine), the latter is more basic. Steric effect plays an important role in deciding the relative base strength among amines in aqueous medium. Comparision between 10 amines:

If we look to the pKA data for MeNH2(10.62), EtNH2(10.7), n-PrNH2(10.54), i-PrNH2(10.63), n-BuNH2(10.6), s-BuNH2(10.56) and t-BuNH2(10.68), we do not feel like comparing between them. The data sources are so scattered and the values are so close, i refrain myself giving any trend for you for examination purpose. In stead , i shall dare say that the primary aliphatic amines have nearly same basicity.

Conclusion: We do not find any aliphatic amine which is weaker than NH3.

Dr. S. S. Tripathy General Organic Chemistry-Part I 33

RESONANCE(R) / MESOMERIC(M) / CONJUGATION EFFECT:

If you really have not studied about resonance before, then please read the introductory part of resonance in the chapter ‘Chemical Bond” before you read further. Let me remind out the salient points on R- or M-effect. (1) Resonance is the delocalisation of π-electron in a conjugated system. (2) More the number of equivalent Resonance Structures(RSs), more is the extent of electron delocalisation and hence more is the stability of the species, hence more is the resonance energy(RE). (3) Resonance changes the bond order and bond length in molecules and ions. Also the heat of hydrogenation or combustion of a R-stablised compound is numerically less than the calculated value from any RS. (4) Number of resonatng structures = Number of conjugating units +1

Type of Conjugating Units: Only when the two conjugating units are separated by one single bond, then resonance/conjugation/mesomerism operates. (a) a π-bond with another π-bond

CCCC CCCC (b) a π-bond with an empty p-orbital(+ve charge)

CCC

(c) a π-bond with a filled p-orbital (–ve charge or neutral)

CCC CCX (d) a π-bond with with a p-orbital containing an unpair electron(free radical)

CCZ In these cases, p-electrons are delocalised by resonance. We can draw two RSs for each case and the actual structure of the species is hybrid of the contributing/cannonical/resonance structures. The RSs are interconvertible by arrow marks as explained before in ‘chemical bond’. If more number of conjugating units extend the conjugation, then number of RSs will be equally more and the delocalisation and stability will be hence more.

Application of R-Effect: (a) Stability of allyl, benzyl and acyl carbocations: (Explained before) (b) Stability of allyl and benzyl carbanions (Explained before) (c) Stability of ally and benzyl free radicals (Explained before) (d) Relative acid/base strength: Examples: 1. Carboxylic acids versus Phenols and Alcohols:

H–COOH > R–COOH > Ph-OH > R-OH We explained before why phenols are more acidic than alchols by using I-effects and also why other carboxylic acids are weaker than formic acid by using +I effect. But why carboxylic acids Dr. S. S. Tripathy 34 General Organic Chemistry-Part I are stronger than phenols, can only be explained by R-effect in their conjugate bases. RCOO–(carboxylate ion) is more stablised by resonance delocalisation. It has two equivalent RSs and the extent of delocalisation is 50%. PhO–(phenoxide) ion although have four RSs, three of them in which C-atom carries –ve charge are less stable and less contributing to the hybrid. Hence the extent of charge delocalisation is smaller, although the numbr of RSs is greater. In case of RO–(alkoxide ion), +I effect of R– group destabilises the ion and hence alcohols are least acidic.

- 1 2 O O O

RC RC RC 1 - 2 O O O

- O O O O O - -

-

Due to greater extent of delocalisation in RCOO– ion than in PhO– ion, PhOH is a weaker acid than RCOOH. RO– is destabilised by +I effect of R– group and hence it is the weakest among them. (N.B: Do not confuse with the symbol ‘R’, sometimes used for resonance effect and some other times used to represent alkyl group.) (e) Change of Bond Order(BO) and Bond Length(BL):

Buta-1,3-diene:

1.33A 1.48A 1.33A 1.54A 1.33A CH2 CH CH CH2 H3CCH3 CH2 CH2 butadiene ethane ethene (conjugated diene) A pure C–C in ethane has a bond length of 1.54Å while a pure C=C has bond in ethene is 1.33Å, while in buta-1,3-diene, the terminal C–C lengths are nearly the same 1.34Å(read 1.34Å in the above structure, in stead of 1.33) while the middle C–C is convincingly less than a single bond length. It is 1.48Å in stead of 1.54Å. This is possible due to conjugation or resonance. We can draw three RSs for butadiene, including the non-ionic structure. Because of its symmetrical structure, an additional RS has come up here, otherwise there should have been two RSs for the two conjugating units.

CH2 CH CH CH2 CH2 CH CH CH2 CH2 CH CH CH2 IIIIII CH2 CH CH CH2

Dr. S. S. Tripathy General Organic Chemistry-Part I 35 RS III is obtained just by polarising the electron pairs in the anticlockwise direction(not shown). But RS (II) and RS (III) together contribute very less because they are ionic while RS-I is non- ionic. But due to contribution of both II and III, the net polarity in the hybrid is zero at each terminal carbon atom. The molecule is non-polar(s-trans). But because of some contribution of two such ionic structures the middle C–C aquires partial double bond character and its bond length is 1.48Å, in stead of 1.54Å. But due to dominant contribution of RS-1, the terminal C=C character is almost retained. The bond length remains nearly the same. Here bond order is not the exact arithmetic average from the RSs, as the the latter two RSs contribute very less. If the RSs would have been equivalent like the case of RCOO–, then BO and BL would have been the exact average. You can look at the oribtal diagram where you can see a partial overlap of the internal p-orbital to give partial π-bonding to the middle C–C. s-trans conformation(which is stable) is shown below. Because of partial double bond character, there is appreciable barrier to rotation, for which s-trans cannot easilty convert ot s-cis conformation.(s-trans means the two C=C are trans w.r.t to the middle single bond)

π π Below you can have a look to the four MOs( 1 – 4) formed by the combination of the four p- π π orbials carrying the four electrons. The lower two ( 1, 2)) are BMOs and the higher two π π π ( 3 – 4) are ABMOs. In the ground state two electrons are in 1 having no node and another π two in 2 having one node. Have a look below. π π 2- is called HOMO(Highest Occupied MO), while 3 is called LUMO(Lowest Unoccupied MO) or LVMO(Lowest Vacant MO). Concerted reactions like Diel’s Alder reaction takes place from HOMO while in some others it takes place from LUMO( diradical). No further discussion will π π be made on this. 3 has 2 nodes while 4 has 3 nodes.

Heat of Hydrogenation: Ethylene has a heat of hydrogenation of –32.5 kcals/mole(–136 kJ/mole). Hence for two C=C, present in buta-1,3-diene the calculated value is 2 × 32.5 = – 65 kcal/mole, Can you guess what is the actual value of heat of hydrogenation of butadiene ? It is –57 kcals/mol. Hence this decrease in the value is due to stabilisation by resonance. Dr. S. S. Tripathy 36 General Organic Chemistry-Part I Penta-1,3-diene:

1 2 3 4 5 1 2 3 45 CH2 CH CH CH CH3 CH2 CH CH2 CH CH2 penta-1,3-diene penta-1,4-diene (conjugated) (unconjugated)

Peta-1,3-diene is conjugated and resonance operates there. Due to that, C2–C3 bond length will be about 1.48Å, in stead of 1.54Å. This exists as E and Z-isomers, in which the former is more stable. C4-C5 has length close to 1.54Å , indicating that it does not belong to the conjugated system. Each of the Z and E isomers is polar and has dipolome moments 0.68 and 0.50D respectively. We can draw two RSs like buta-1,3-diene for it.

CH2 CH CH CH CH3 CH2 CH CH CH CH3 - + CH2 CH CH CH CH3 The other ionic RS with reversal of poles is possible, but that will contribute still less. Since

CH3– group is electron donating group(+I), the second RS is more significant than the other not drawn. Due to its contribution to the hybrid, the compound is polar and has a net dipole moment. However cis and trans have different values of the moment.

H2C CH H2C CH H CH3 CC CC H CH3 H H E-penta-1,3-diene Z-penta-1,3-diene =0.5D  = 0.68D Each of them is in its s-trans conformation(more stable). About s-cis, we have discussed in our ‘stereoisomerism’ chapter. The E-penta-1,3-diene has a heat of hydrogenation of –54.1 kcals/mole, which is numerically less than even buta-1-3-diene. We shall know the reason for it later, when we study hyperconjugation for which additional stability is gained by penta-1,3-diene. The value for Z- penta-1,3-diene would be numerically slighter greater than E-isomer. I do not have its data.

Penta-1,4-diene is unconjgated and has no geometrical isomers. It is symmetrical molecule and hence is non-polar(dipole moment= 0D). It has two pure C=C and two pure C–C bonds. So no change in the bond orders and lengths are noticed in such compound. The heat of hydrogenation is –60.8 kcals/mole, which is numerically greater than penta-1,3-diene, in which there is resonance. Note that it is numerically less than the double of the value for ethylene(65 kcals/mole) as it has more stabilisation than ethylene due to hypercojugation(to be discussed later) Conjugated polyenes: Greater the extent of conugation, greater is the extent of delocalisation. For example, in hexa- 1,3,5-triene there will be 6 MOs formed by the LCAO of six p-oribitals, out of which 3 will be BMOs and 3 will be ABMOs. Similarly in conjugated tetraene, there will be 8 MOs and so on. More the extent of conjugation, the number of MOs and hence the energy required for the excitation of electron from HOMO(higest occupied molecular orbital) to LUMO(lowest unoccupied MO) in the MO set-up, will be decreased and will fall in the visible range. This π−π* transition(HOMO to LUMO) gives rise to different colours to different compounds, depending on the absorption of radiations and their complimentary colours for our observation. The compound β-carotene which is present in carrot is orange in colour due to this extended conjugation. It has 11 conjugated double bonds !!!!!! Dr. S. S. Tripathy General Organic Chemistry-Part I 37

(β-carotene)

In all other compounds where there is resonance, BO and BL get changed. Before we go to few other examples, let us introduce two types of groups which produce R- effect. Types of R-(M-) groups: (a) +R/+M Group: Those produce electron donating effect through resonance. Such groups contain a heteroatom having at least one lone pair.

,, ,OCOR , X (halo) NH2 OH OR , –NHCOR, –NHR, –NR2 etc. Note that all these groups in terms of I effect are electron withdrawing (–I groups) in nature. So they have opposite electron delocalisation effects in Inductive and Resonance. When heteroatom’s size is small eg. N, O, F, the +R effect dominates over –I. However for larger size heteroatom like S, Cl, Br,I, etc. –I is the dominant effect. The overlpap p-oribitals become effective only when size of the heteroatom is small and in such case the +R effect in the conjugated system takes over the –I effect working via sigma bonds. (b) –R( -M) groups: Those produce electron withdrawing effect through resonance. Such groups are called –R/–M groups. Such groups must have a multiple bond(double or triple bond) with at least one heteroatom like, O or N. Moreover there should not be any lone pair on the first atom of the group.

+ –NO2, –CN, –COOH, –COOR, –SO3H, –CHO, –COR, –NR3 etc.

Note thal all –R groups are also –I in nature. The two effects support each other unlike the +R groups, which is opposed by –I effect. Between –M and –I, no doubt the former effect is more pronounced than the latter.

N.B: The use of +R/M and –R/–M groups is mostly done in benzene and related aromatic compounds. However, i felt like introducing these terms now. See these examples. Examples: (1) Vinyl chlorde:

CH2 CH Cl CH2 CH Cl III - + CH2 CH Cl –Cl group produces +M effect onto the rest part of the molecule. Since it is a large size atom, the resonance is a minor effect. Moreover RS-II is less stable and less contributing because it is ionic and +ve charge lies on a more electronegative Cl atom. But due to some resonance, the bond orders get changed. C–Cl bond aquires a partial double bond character, hence it is stronger than C–Cl bond in ethyl chloride.

Dr. S. S. Tripathy 38 General Organic Chemistry-Part I

C–Cl BL in CH3–CH2–Cl = 1.789Å

C–Cl BL in CH2=CH–Cl = 1.736Å You clearly find the decrease in bond length of C–Cl bond in vinyl chloride due to +M effect of Cl atom. But the decrease is very small as the resonance effect is small. Dipole Moment: +M + - + - CH2 CH Cl CH3 CH2 Cl -I -I  = 1.44D  = 2.06D Since the dominant effect is –I in this case(Cl is large size atom), there is dipole moment from C to Cl atom. In vinyl cloride this dipole due to –I effect is decreased by some +M effect working in opposite direction. Hence its net dipole moment is much less. In ethyl chloride there no +M effect to oppose and hence its dipole moment is much greater. (2) Prop-2-enal(acraldehyde) vs. Propanal:

CH2 CH CH O CH2 CH CH O I + - II CH2 CH CH O In this case, -CH=O group produces –M effect onto the rest of the molecule. RS-II is less stable because carbon is a sextet and it is an ionic RS. But due to some contribution of RS-II acraldehyde δ has a partial double bond character in C1–C2 bond. Because of that also, the electrophilicity(+ ) character of the carbonyl carbon is greatly reduced. + - CH3 CH2 CH O (propanal) more electrophili In propanal, there is no resonance and hence BO/BL are not changed. Moreover, the carbonyl carbon is more electrophilic as +δ charge is more.

Stability of carbocation by +M effect of alkoxy group:

CH3 OCHCH2 CH3 CH3 OCHCH2 CH3 I II

Here CH3–O-(methoxy) group produces +M effect on the carbocation. RS-II is more stable and more contributing. We have discussed this before. Since –O– is a small size atom, here +M effect is more dominating than –I effect. Here we cannot talk about dipole moment and compare like we did for vinyl chloride as it is a reactive intermediate, and not a stable species.

SAQ: Draw RSs for the compounds CH3–O–CH=CH2(methyl vinyl ether) and CH2=CH-NH2(vinyl amine). Comment on the BOs for those changed due to R-effect. Indicate the type of R effect

(+ or –) shown by the MeO– and NH2– respectively. Solution:

CH2 CH O CH3 CH2 CH O CH3 I II

- + CH2 CH O CH3 Dr. S. S. Tripathy General Organic Chemistry-Part I 39

CH3O– group shows +M effect and for that the bond length of C–O bond on the vinyl side is shortened. C–O bond length in dimethyl ether is 142 pm. In methyl vinyl ether, one C–O(on the Me side), the bond length is same but on the vinyl side it is slightly shortened due increase in bond order(data not given). You can also this shortening of bond length without invoking R- effect. You can say that due to sp2 hybidisation in the vinylic carbon, the bond pair is more closely bound and hence bond length is shortened.

CH2 CH NH2 CH2 CH NH2

Due to +M effect of –NH2 group, the bond length of the C–N bond is shortened compared to ethyl amine. You can also explain this to be due to sp2 hybridisation of carbon without bringing in R-effect.

Acidic Nature of α-H atom w.r.t a –M group: We have already discussed that α- H w.r.t an electron withdrawing group is acidic in nature. Now we shall express the same thing bit differently. α-H atom w.r.t to a –M group is acidic in nature as the its conjugate base(carbanion) is resonance stabilised.

H O O O B CH2 N CH2 N CH2 N - (BH) O O O nitromethane

SAQ: Draw the RSs of the conjugate bases(carbanions) of the following compounds.

(a) CH3CH2CN (b) CH3CH2CH2CHO (You look for the α-carbon for making a carbanion and then draw the RSs.

SAQ: Between vinyl choride and chlorobenzene, which has a shorter C–Cl bond length and why ? Solution:

Cl 1.69 A

CH2 CH Cl 1.73A

The C–Cl bond in chlorobenzene is shorter than that in vinyl choride. In terms of hybridisation of carbon atoms, both have the same status(sp2). Then we have to either say here Ph– group is showing more –I effect than vinyl for which the electron deloclaisation is more in chlorobenzene. Or, we can say the resonance delocalisation in chlorobenzene is more, as we can draw four RSs like we did for phenoxide ion before. But you know already that in this case, the resonance effect is subsided by prominent –I effect. Nevertheless,when the question of comparision comes, we can use relative R-effect to explain the shortening of C–Cl bond length. Note that due to this it is more difficult for chlorobenzene to undergo nucleophilc substituion than vinyl chloride. Of course, alkyl chloride is the best candidate for such reaction, as the C–Cl bond is the longest(weakest). We shall discuss about this in details later. Dr. S. S. Tripathy 40 General Organic Chemistry-Part I Basicity of Aromatic N-bases:

Aniline: Aniline is less basic than ammonia and hence all aliphatic amine. How to explain this. Here we can confidently bring in +M effect of –NH2 group for a pronounced electron delocalisation. Due to this, the lone pair is less available on N- atom.

NH2 NH2 NH2 NH2

+ NH2

- - ( pKA =4.58 NH3= 9.26)

-

Although the three ionic RSs are less contributing to the hybird, +M effect of –NH2 group is responsible to delocalise the lone pair on N-atom into the benzene ring. Here you cannot explain 2 the basicity by taking the sp hybridisation of carbon atom bonded to –NH2 group as you could do it in chlorobenzene to show shortening of bonds.

While NH3 has a pKA of 9.24, aniline has the corresponding value of 4.58. Can you feel the remarkable difference in basicity. Aniline is a much weaker base than ammonia and all aliphatic amines. This is precisely due to resonance delocalisation. For that reason, there is –δ charge created on the two ortho positions( position 2 on either side of C-1) and para position(position 4). We shall be returning to this later.

Pyrindine:

pKA = 5.23

N N sp2 hybrid N N Pyridine is an aromatic nitrogen base, which is more basic than aniline but less basic than ammonia and aliphatic amines. Why ? The lone pair on N-atom occupies a sp2 hybrid orbital which is not a part of conjugated system i.e not counted for the aromaticity of having (4n+2) π-electrons(to be discussed later). So it is not delocalised like aniline, for which it is more available and hence more basic. But since it is located in a sp2 hybrid orbital, it is relatively less available than ammonia and aliphatic amines, in which the lone pair is present in a sp3 hybrid orbital. Pyridine has two RSss like benzene.

Dr. S. S. Tripathy General Organic Chemistry-Part I 41 Pyrrole:

NH NH NH

NH NH

- -

pKA= - 0.27 - - + NH Pyrrole is aromatic as the lone pair on N- atom is a part of the (4n+2) conjugated pi- electrons. It is a hybrid of the above five RSs and hence the lone pair is more extensively delocalised. In 3 aniline, the –NH2 was not a part of aromatic ring and the lone pair is present in a sp hybrid orbital as against pyrrole in which the lone pair is present in an unhybridised p-orbital and N- is sp2 hybridised like that in pyridine. But the difference between pyrrole and pyridine is that the lone pair is present in a unybridised p-orbital to be a part of conjugated system in pyrrole, while in pyridine the lone pair occupies a hybrid orbital to remain located and not take part in the conjugation.

Basicity: Pyrrole is far less basic than aniline. The corresponding pKA value is –0.27(Some literature gives it ‘0’). This unusually low basicity is due to greater resonance delocalisation of lone pair being part of the ring system. Conclusion:

NH2

> RNH2 > NH3 > > N NH pKA 9.26 5.23 4.58 - 0.27

Some other nitrogen bases:

N O

NH NH NH CH3 N CH3 NH piperidine pyrrolidine imidazole e pKA 2,6-dimethylpyridine morpholin (conjugate acids) 11.0 11.2 7.0 6.7 8.3

(CH3)2N N(CH3)2 NH NH CH N diphenyl amine aziridine 3 N N(CH3)2 pKA heptamethylisobiguanide (conjugate acids) 0.8 8.0 17.0 Dr. S. S. Tripathy 42 General Organic Chemistry-Part I

O

RCN RN O alkyl cyanides nitroalkanes pKA (conjugate acids) - 10.0 - 12.0

NH2 O O

H2NOH H2NNH2 H2N C NH H2NCNH2 RCNH2 hydroxyl amine hydrazine amides pKA guanidine urea (conjugate acids) 5.9 8.0 13.6 0.1 - 0.5

Analysis: 1. Why piperidine and pyrrolidine are so highly basic compared to their aromatic counterpart pyridine and pyrrole ? They are even stronger than many aliphatic amines. First of all N- is sp3 hybridised and there is no aromaticity, secondly the cyclic nature of the compound with restricted rotation gives more +I effect than aliphatic amines. (2) Why imidazole is much more basic than pyrrole, both being aromatic ? It because the lone pair on 2nd N atom is not a part of conjugated system(like pyridine) and is responsible for the greater base strength. (3) Why morpholine has lower basicity than piperidine ? That is because of –I effect of -O- atom.

(4) 2,6-dimethylpyridine is more basic than pyridine is due to +I effect shown by the two CH3 group. (5) Diphenyl amine is much less basic than aniline because the lone pair on N atom is much more delocalised by two benzene rings. The number of RSs is 7(in stead of 4 four aniline).

(6) Aziridine is less basic than NH3 because of ring strain. 3-membered ring has high angle strain for which percentage of s-character becomes more, hence less basic.

(7) Hydroxyl amine is less basic than NH3 because of –I effect of -OH group.

(8) Why hyrazine is weaker base than NH3 ? Its an interesting question. Let me answer it on the relative stability of their conjugate acids.

H2NNH3 NH4 - I effect less stable

The conjugate acid of hydrazine cannot be stabilised by +M effect the other -NH2 group, as it

(ammoinum N) cannot expand its octet. Hence the intrinsic –I effect of –NH2 group destabilises + it. No such destabilising effect is present in NH4 . Hence hydrazine is a weaker base. (9) Why urea is so less basic ? Its because, the lone pair is delocalised by the –M effect of -CO- group, thus not very much available. (10) Why aliphatic amides are so less basic ? In fact they are neutral compounds. This is because the lone pair is delocalised by the resonance effect. (11) Guanidine is so highly basic because of two sp3 hybrid N atoms despite a bit of resonance existing in the molecule. (12) Hepatamethylisobiguanide is so highly basic, because of so many sp3 N atoms. (13) Alkyl cyanide’s basicity is really laughable !!!! Its because N- is sp hybridised. Nitroalkanes or nitrobenzene is still less basic. In fact, in this case, N-does not carry any lone pair. It is for O-atoms basicity can be thought of. Dr. S. S. Tripathy General Organic Chemistry-Part I 43 Some neutral Oxygen bases:

I really shy away from the discussion on neutral oxygen bases like H2O, ROH, ROR, aldehydes, ketones etc. Most of them have either acidic H or are far too less basic, to be branded as neutral bases. The lone pair is bound to a more electronegative O atom and is less available for accepting a H+. So discussion on their basic property appears bit superfluous. However, in certain organic reactions, compounds like ketone, aldehyde, alochol are protonatd. So the relative base strengths of these neutral compounds may be required at certain time. So let us discuss more on it. I would now like to take you to some physical chemistry area involving calculation. This, i remember, has not been included in the ‘ionic equilibrium’ chapter. I shall sometime, append this there, while making revision.

+ SAQ: Caluclate the pKA for H3O and how strong acid is hydronium ion compared to other acids. Solution: Approach 1:

pKA and pKB of H2O is each 15.26. Let us take the acid/base dissociation of H2O.

H2O + H2O H3O + OH

    [H 3O ][OH ] [H3O ][OH ] KW KC   KC [H 2O]   [H 2O][H 2O] [H 2O] 55.5

1014  K (H O)  K (H O)   pK (H O)  pK (H O) 15.26 A 2 B 2 55.5 A 2 B 2

+ Acid dissociation of H3O :

H3O + H2O H2O + H3O Acid Conjugate base pKA = - 1.74 pKB= 15.26

Since the product of KA of an acid and KB of its conjugate base is KW.

K A (Acid) K B (conj.base)  KW  pK A (Acid)  pKB (conj.base) 14 + So H3O is strong acid as its pKA is –ve. But it is less strong than HCl(pKA = –7), HNO3, H2SO4 and other known strong acids as their pKA values are still more –ve.

2nd Approach:

H3O + H2O H2O + H3O

  [H 2O][H3O ] [H 2O][H 3O ] KC   KC [H 2O]   55.5    K A  55.55 [H3O ][H 2O] [H3O ]

 pK A  log(55.55)  1.74 – SAQ: Find the pKB of OH . – Solution: Since pKA of H2O is 15.26, pKB of its conjugate base i.e OH is –1.74.

+ – N.B: In this case you found that pKA[H3O ] = pKB[OH ] = – 1.74. It is not true in every case.

Dr. S. S. Tripathy 44 General Organic Chemistry-Part I

+ – SAQ: Given that pKA (NH3) = 38, Find the pKA of NH4 and pKB of NH2 . Are they same like the case of H2O ? Solution:

NH3 + H2O NH2 + H3O

– – pKA(NH3) = 38 (given); Hence pKB( NH2 ) = 14 – 38 = – 24. So NH2 is a very strong baase.

NH4 + H2O NH3 + H3O

+ Since pKB(NH3) = 4.74 (we know it before), then pKA(NH4 ) = 14 – 4.74 = 9.26 + – So what you found ? Like the case of H2O, pKA(H3O ) = pKB(OH ), here we do not find the same – + – for NH3. While pKB(NH2 ) is –24, pKA(NH4 ) is + 9.26. This means NH2 is a very strong base, + + while NH4 is a weak acid.(much weaker tha H3O ).

ACID-BASE Reaction:

A stronger acid (lower pKA value) can displace a weakr acid(higher pKA value) in an acid-base reaction. The acid-base both should be of BL type.

Similarly a stronger base(lower pKB balue or higher pKA of its conjugate base) can displace a weaker base(higher pKB value or lower pKA of its conjugate acid). + Acids which are stronger than H3O like HCl, HNO3 etc. are almost completely ionised in water.

The equilbrium constant for an acid-base reaction is obtained by taking the ratio of the two KA values from LHS to RSH ( Not RHS to LHS, as is normally used to determine Keq) For any BL acid - BL base reaction, you can find whether it is a highly forward driven reaction or backward driven reaction by comparing the KA values between LHS acid and RHS acid , or

KB value of LHS base and RHS base. I shall be using KA values for analysis.

The equilibrium constant(KC) of a acid-base reaction is obtained as follows.

K A[ACID]LHS KC  K A[ACID]RHS

Note that this ratio is not the conventional method of finding KC . For that we take the ratio of RHS to LHS. But that makes use of concentrations,. In this case, we are using two dissociation constants. Hence the ratio LHS to RHS.

If KC >>>1 then, it is forward driven i.e product favoured reaction. If KC <1, it is backward driven reaction or reactant favoured reaction.

Same conclusion, we shall get by comparing the KB values of the LHS and RHS bases.

Examples: 1.

HCl + H2O Cl + H3O pKA-7 - 1.74 K 7 1.74 A 10 10

7 K A[LHS) 10 5.26 KC   1.74 10 , K A[RHS] 10

Since KC of the above reacion is so high, the equilibrium lies almost entirely towards the right. So it is nearly 100% ionised. Dr. S. S. Tripathy General Organic Chemistry-Part I 45 2.

CH3COO + H OEt CH3COOH + EtO 15.9 4.74 Can the above acid-base reaction happen ? Is it a forward driven reaction? The answer, from the first sight, is NO. A weaker acid (EtOH) cannot displace a stronger acid(CH3COOH). We can find the KC value for the reaction. 1015.9 K  1011.16 C 104.74

So the reaction is not feasible as KC is so small. An alcohol cannot protonate a carboxylate ion to obtain neutral carboxylic acid. For that to happen, we have to use a streong acid having pKA value less than 4.74. 3.

CH3COOH + NH3 CH3COO + NH4 4.74 9.26 + Prima facie evidence suggests that a stronger acid(CH3COOH) can displace a weaker acid(NH4 ). 104.74 K  104.52 C 109.26

Since KC value is large, this is product driven reaction. Hence ammonium acetate salt will be formed when acetic acid reacts with ammonia.

+ + SAQ: Determine the pKA value of CH3OH2 ( or of any RCH2OH2 ) i.e conjgate of ROH. Given pKA of CH3OH = 15.5. Solution:

Like in case of H2O, in ROH too, the pKA value of protonated alcohol can be obtained by substracting the pKA of ROH(in fact it is same as pKB of ROH) from 14. This is because like water, alcohols have also their pKA and pKB values are same. One is protonating H2O(When ROH acts as acid) and the other is protonating ROH(when it acts as base) involves nearly the same free energy change. The case of NH3 is different. NH3 as a base, is much sronger(pKB =

4.74) but as an acid is much weaker(pKA = 38). + pKA (CH3OH2 ) = 14 – 15.5 = – 1.5

CH3OH + H2O CH3OH2 + OH

pKB(CH 3 OH) = 15.5 pKA (CH 3 OH 2 ) = - 1.5

– This is the same as the pKB of CH3O ( –1.5)

+ – SAQ: What is pKB value of H3O and pKA value of OH ?

2- O (s) + H2O (l) 2 OH (aq), (equilibrium lies to right) pK = - 22 B pKA(OH ) = 36

Dr. S. S. Tripathy 46 General Organic Chemistry-Part I

2+ + H3O + HSbF6 H4O + SbF6 super acid (eq. lies to the left) KC < < << 1 + Although virtually protonation of H3O does not occur, this reaction has been found to proceed + to some extent in sulfolane (tetrahydrothiophene-1,1-dioxide) solution. So pKB of H3O is highly positive. ______4.

O

RCR' ROR' ROH O pKA - 3.6 - 2 10 (conjugate acids) - 7.3 (approx. values) Excepting phenoxide ion which is farely a strong base, though weaker than OH–. Alcohols are still stronger bases(relatively) than ethers. We stop further discussion on this and switch on to Hyperconjugation effect.

HYPERCONJUGATION(NO BOND RESONANCE): H-Effect.

When a C–H sigma bond remains in conjugation with (a) a vacant p-orbital(unhybridised) on a sp2 hybrid carbon( alkyl carbocation) OR (b) a π- bond of C=C (alkenes) OR (c) an unpaired electron in a p-orbital(unhybridised) on a sp2 hybrid carbon (free radical), electron delocalisation does take place but to a smaller extent compared to a π- bond conjugating with above units. Hyperconjugation is a case of σ-p conjugation while resonance is a case of π-p conjugation. So H-effect is applicable mostly to (a) carbocations (b) alkenes (c) carbon free radicals.

H H H

(a) CH2 CH (b) CH2 CH CH2 (c) CH2 CH2

It is also called NO BOND RESONANCE as each contributing structure(other than the oringinal one) contains one NO BOND strutcure. Electron delocalisation will occur via this σ-p conjugation which will stabilse the species and alter the BO and BL. It is less pronounced effect than R- effect, but more pronounced than I-effect.

Requirment for H-effect: (i) The species should have a sp2 hybrid carbon carrying unhybridised p-orbital(carbocation, alkene C=C and carbon free radical) (ii) There must be one α-H atom in a sp3 hybrid carbon with respecto to +ve charge(carbocation), C=C(alkene) or radical centre(free radical). Dr. S. S. Tripathy General Organic Chemistry-Part I 47

-bond vacant p-orbita

-H atom CC

Due to rotation of C–C single bond, the C–H sigma bonds alternately comes to a near parallel conformation(remain coplanar however) with the p-orbital of th sp2 hybrid carbon. At this position, overlapphing of the sigma bonding orbital happens with the vacant orbital thereby bringing about delocalisation of electron. While drawing the contributing structures, one α-H atom has to be delinked from C–H bond to form form C=C and a H+ ion with NO BOND beteween H+ and α- carbon.

No. of Hyperconjugation(HC) structures = no. of α- H atoms + 1

Each α- H atom will be involved in the delocalisation process and contribute one structure. More the number of α-H atoms, more is the number of HC structures, and hence more is stability of the species. Isotope Effect: Since the bond energy amond sigma bonds is in the order C–T > C–D > C–H the extent of hyperconjugation varies in the reverse order. C– H > C–D > C–T (hyperconjugation order) Concluding defintion: Hyperconjugation is the interaction of electron in a sigma bond(C–H or C–C) with an adjacent vacant or paritally filled p-orbital (carbocation and carbon free radical respectively) or antibonding π MO(in case of alkene), antibonding σ-MO or filled π-MO.

(i) Relative Stability of Alkyl Carbocations:

H a Ha Ha Ha

H C CH2 H C CH b 2 H C CH2 HCHC 2 b b b H c H H c H c c 4 HC /contributing structures In the ethyl carbocation shown above, there are 3 α-H atoms, so we could draw four (3+1=4) hyperconjguation structures. Some authors term it as Resonance Structures(RSs). But i would prefer to use a different term i.e HC structure, as σ-p conjugation is less pronounced than a π- p conjugation. The contributions are much smaller compared to π-p conjgation. However, this effect is more powerful than I- effect(delocalisation through σ-bonds only). But we shall see its effect in alkenes, how it changes the BO/BL. In carbocations, we can compare the relative stabilities of alkyl carbocations by using HC effect(we can call here +H effect of CH3 group).

Dr. S. S. Tripathy 48 General Organic Chemistry-Part I Relative Stabilites of Alkyl Carbocations:

  CH 3 CH3    > > CH3 C CH3 CH CH3 CH2 > CH3

CH3 13 HC strs 7 HC strs 4 HC strs NO HC 30 20 1010 There are 12 α-H atoms in tert-butyl carbocations(30 carbocation), and 6 α-H atoms in isopropyl 0 α 0 α carbocation(2 ) and 3 -H atoms in ethyl(1 ) carbocation and no -H atom in CH3 carbocation(also 10). So the number of contributing structures is one more than these numbers respectively. So the most stable is the 30 carbocation having maximum HC effect and least stable is methyl carbocation as it has no HC stabilisation. Note that we have explained the stability of carbocations by using +I effect. Now we explain this by using +H effect, which is more pronounced that +I effect. The carbocation’s stability is primarily due to hyperconjugation, which is supported by +I effect to provide additional stability. Note that the unusual stability of tert-butyl carbocations over many other carbocations stabilised by resonance effect like allyl carbocation, is not merely due to +I effect. It is primarily due to +H effect. (ii) Relative Stability of Akenes: Alkenes containing α-H w.r.t C=C, on either side of it are stabilised by electron delocalisation through hyperconjgation. This σ-bonding orbital of C–H bond can interact with π* anitbonding vacant MO of C=C or filled π BMO of C=C.

Ha Ha

H C CH CH H C CH CH b 2 b 2

Hc Hc

Ha Ha

H C CH CH H CCHCH2 b 2 b H Hc c 4 HC structures

Though a σ-bond conjugating with a π-bond or p-orbial sounds unacceptable, as σ-bond is a stronger but it does happen, which is evidenced in the change in BL in alkenes, also the different heats of hydrogenation that each produces. Before giving experimental data, we take up the following. Relative Stability of Substituted Alkenes:

Tetrasubstituted > trisubstituted > disubstituted > monosubstituted > CH2=CH2

   CH3 CH3 CH3       CH3 C C CH3 > CH3 CH C CH3 > CH3 CH CH CH3 > IIIIII 13 HC structures 10 HC structures 7 HC structures

 CH3 CH CH2 > CH2 CH2 IV V 4 HC structures No HC Dr. S. S. Tripathy General Organic Chemistry-Part I 49 Each of the five alkenes given before, contains one C=C, but their stabilites are different, the BL of C=C and C–C are different. If BO of C=C in ethene (V) is 2, all the rest have BO less than 2 because of hyperconjugation. Similarly BO of C–C in all the cases except ethene(which has no C–C), becomes >1. More the number of α-H atoms, more is the number of HC structures and hence more is the stability of alkene and less is the BO of C=C. and more the BO of C–C. Stability order : I > II > III > IV > V BO of C=C : I < II < III < IV < V BL of C=C: I > II > III > IV > V BO of C–C : I > II > III > IV BL of C–C : I < I < II < III

This can be compared the actual BL data with a pure C–C : 1.54Å and pure C=C : 1.33Å. I do not have the BL data for all these, but for sure the C=C BL in I would be the greatest (BO least) which would be less than 1.54Å and least(BO greatest) in propene, which will be little more than 1.33Å. Simiilary the C–C single bond length will be less 1.54Å in all cases(except ethene, which does not have a C–C). I have the data for propene. Have a look.

H H 1.506A C1 H 1.344A 1.106A C C 2 H 3 H H

You see that C1=C2 length has been 1.344Å, which is slightly greater than 1.33Å in ethene.

Similarly C2–C3 length has been 1.506 which is slightly smaller than 1.54Å.

Stability of Substituted Alkenes (Taking cis and trans isomers of alkens and other structural isomers):

H CH3 (CH3)2CC(CH3)2 > CH3CH C(CH3)2 > CC > CH2 C(CH3)2 H3C H 119 H.H(-ve) 111 113 115 isobutylene KJ/mole trans-but-2-ene H3C CH3 > CC > CH3CH CH2 > CH2 CH2 H 126 120 H 137 cis-but-2-ene

The numerical values heat of hydrogenation has been given below each structure. Propene is more stable than ethene by 11 kJ/mole. Tetramethylethylene(compound I) is more stable than ethene by 26 kJ/mole and so on. Cis-but-2-ene is less stable than trans-but-2-ene by 5 kJ/mole because there is steric strain in cis- but-2-ene as the two methyl groups lie on the same side as against in trans isomer in which they lie on the opposite sides. Note that isobutylene(2-methylprop-1-ene) and cis- but-2-ene have the same number of HC structures, but they are equally stable and both are less stable than trans-but-2-ene. If you compare the heat of hydrogenation data, isobutylene will be found to be little more stable than cis-but-2-ene. Dr. S. S. Tripathy 50 General Organic Chemistry-Part I (More the sability less is the numberical value of heat of hydrogenation and heat of combustion. Also the heat of formation will be greater than sum of all the bond dissociation energy of the compound) Hyperconjugation of σ-bond with π-bonds in other compounds:

H H H O H C CCH H C CN H C N 1.46A H H H O propyne methyl cyanide nitromethane We already know the α-carbon w.r.t a –M group is acidic as the conjugate base(carbanion) at that position is resonance stabilised. But in the absence of a base, i.e in the neutral compounds also the BO/BL are altered. Even in propyne, C–C BL is 1.46Å which is less than 1.54Å. In buta- 1,3-diene too, the middle C–C BL is 1.46Å. But that is explained by resonance. But in propyne,we cannot have any resonance, in stead there is hyperconjguation. Of course you can explain this by saying that one of the C- atoms in this bond is sp hybridised and hence there is a decrease in bond length. OK fine. But what about poloarity i.e dipole moement ? Same is the case with other two compounds shown.

Dipole Moment: 1. Alkenes and Alkynes: The actual dipole moments of propene is 0.49287D, which is greater than the calculated dipole moment of propene, without considering the polar HC contributions discussed before. Similarly the dipole moments of propyne, nitromethane, methyl cyanide and similar compounds are found to be greater than their expected calculated values. This proves the existence of hyperconjugation.

(iii) Relative Stability of Alkyl Free Radicals: Although we had already explained the order stability (30 > 20 > 10 > Me) on the basis of +I effect analogous to carbocations, as carbon free radicals also is incomplete octet, their relative stabilities can be best understood by HC effect. See below.

Ha Ha Ha H a

H C CH2 H C CH H C CH H CCH b b 2 b 2 b 2 Hc H H c c Hc

Ethyl free radical has 3 α-H atoms and we can draw 4 HC structrues as shown above. Hence it is more stable than methyl free radical as there is no HC effect (no α-H atom).

  CH3 CH3    > CH CH > CH3 C 3 CH3 CH2 > CH3  CH3 10 HC strs 7 HC strs 4 HC strs NO HC 30 20 10 10

Dr. S. S. Tripathy General Organic Chemistry-Part I 51 In tert-butyl(30) there are 9 α-H atoms, in isopropyl(20), there are 6 and in ethyl(10) 3 and in methyl no α- H atoms. MO theory for HC effect: LCAO of σ-bonding MO of α-C–H with π* of C=C occurs to give a lower energy BMO in which two electrons occupy. This lowering of energy stabilises the species. ABMO of this combination remains vacant.

Reverse HC effect ( –H effect) If the hyperconjugation due to C–H bond of an alkyl group will be called +H effect(or simply hyperconjugation), for C–Cl bond it will be called reverse hyperconjugation or –H effect.

Cl Cl

CH2 CH CH2 CH2 CH CH2

Due to reverse H- effect, the bond length of C–C bond is changed in allyl chloride compared to propene. This effect will be more prominently found in benzene ring attached with –CCl3 group which we shall see later.

(Note that application of H-effect in aromatic compounds will be taken up later)

Summary of consequences of Hyperconjugation Effect: 1. Change in BO/BL in alkenes, alkynes and other compounds containg α-H atoms to a – M group. 2. Change in dipole moment: Increase in dipole moment in the above mentioned compounds 3. Stability of alkenes 4. Stability of carbocations 5. Stability of alkyl free radicals 6 Orientation in benzene ring by Alkyl group and -CCl3 group (to be discussed later) 7. Anomeric Effect: In carbohydrate chemistry we shall know that glucosides(methyl glycoside from glucopyranose structure) has two anomers σ and β. α-glucoside is more stable than β, because in α- form the the lone pair p-orbital on O-atom (HOMO: highest occupied MO) overlaps with the antibnding orbital of C–O sigma bond(LUMO: Lowest unoccupied MO) effectively if the

–OCH3 group remains in axial position(antiperiplanar condition). This is hyperconjugation between β a lone pair and a sigma bond. In -anomer, OCH3 group occupies in the equatorial position(not antiperiplanar)

Dr. S. S. Tripathy 52 General Organic Chemistry-Part I

(Note that hyperconjugation effect, now, has been extended in many other compounds like CH2=C– C(–R)=O, where C–R bond enters in hyperconugation with C=C, so as to compete with resonance. Even the staggered conformation of ethane can be explained by the hyperconjugation of one sigma bond with another sigma bond. All these, we do not discuss here). Complete Definition: Hyperconjugation is the stabilising interaction that results from the interaction of the electrons in a σ-bond (usually C-H or C-C) with an adjacent empty or partially filled p-orbital or filled p-orbital to give an extended molecular orbital that decreases the energy of the system and thereby increases the stability of the system. The orbitals used for giving MO is usually HOMO(BMO) of sigma bond with LUMO(ABMO) of the π-system. The reverse is also possible as in the case of anomeric effect shown above.

SAQ: Give the reason for the following stability order among carbocations.

CH3 CH3

CH3 C CH CH3 <

Electromeric Effect (E- effect): Unlike I, M and H effects discussed before, electromeric effect is a temperorary electron delocalisation in a species carrying multiple bond, effected by the approach of a charged species i.e nucleophile or electrophile. The π-bond gets polarized to produce an ion in the substrate. But this process can be reversed by adding another species which will remove the added ion, thereby the original π-bond is restored. – E Effect:

- O O

R C + R' + CN RC R'

substrate nucleophile CN Dr. S. S. Tripathy General Organic Chemistry-Part I 53 In this case a nucleiphile (CN–) attacks a carbonyl carbon(electrophilc centre) of the substrate and the C–O pi-bond gets polarized onto oxygen atom, thereby an oxide ion intermediate is formed. We shall shortly, study that this is the first step in the mechanism of nucleophilic addition reactions. But we can reverse the process by suitable method(to be discussed later) so as as to get back the original carbonyl compound. When the delocalisation of electron takes place away from the attacking species, it is called –E effect. All nucleophilic attacks onto electrophilic centres(+δ) of the substrates come under this category. +E Effect: All electrophilic additions to a multiple bond comes under this category.

H

RCHCHR'+ H RCHCHR nucleophilic substrate electrophile

As the π-bond of the C=C gets polarized and adds onto E+(electrophile), a carbocation intermediate is formed. This process can be reversed by addition a suitable reagent(to be discussed later). Since the electron delocalisation takes place towards the attacking species, it is called +E effect. N.B: In all electrophilic and nucleophilic additions E-effect takes place. But this term will be rarely used in our future discussion. So we do not like to make further discussion on this aspect.

Inductomeric Effect: Like electromeric effect, inductomeric effect is also temporary. When polarization is induced in the sigma bond by the approach of an external charged species, then it is inductormeric effect. This effect is very scantily discussed. We shall not talk about it in future.

OH + - + - CCl CCl

When a nucleophile like OH– approaches an alkyl chloride, the polarity fo C–Cl bond is increased further as the nucleophile comes closer. When it is taken away, the effect is reduced. This is similar to E-effect, but the difference is, in E effect, there is poloarisation of pi bond while in Inductomeric effect, it is polarisation of sigma bond. Both are temporary. (N.B: Guys, you just forget about these two temporary effects for ever !!!!!!)

Steric Effects:

We have already discussed about steric strain – the repulsion between the electron clouds of two neighbouring groups in space produces steric strain or Van der Waals strain in the species and thereby increasing its instability. Eclipsed conformation of butane in which Me- groups are eclipsed is most unstable conformation as the the steric strain is maximum, while the anti- conformation in which the two Me-groups are opposite(anti) to each other is most stable as the steric strain is minimum. So when the two groups come close to each other, the steric strain increases. More the bulk of the group, more is the steric strain. t-Bu– > i-Pr– > Et– > Me– We shall discuss steric effects on the following two heads. (a) Steric Inhibition of Resonance(SIR) (b) Steric Effect in chemical reactions Dr. S. S. Tripathy 54 General Organic Chemistry-Part I (A) Steric Inhibition of Resonance (SIR): When there is severe steric strain in certain part of the molecule, that part goes out of planarity w.r.t the rest part of the molecule. Thus free delocalisation of pi-electron in a conjugated system is decreased. Due to this, the property of the molecule e.g acid and basic strengths are altered. This is called SIR. Don’t be carried away by the term ‘inhibition’. Its truly a misnomer here. Resonance is not often stopped as the literary meaning of inhibition can claim. Rather the extent of resonance is decreased. Yes, of course, in some extreme case, it can be stopped. SIR is often observed in aromatic compounds. I shall be giving just two examples, not more now. We shall be frequently using this term in our future discussions. (1)

COOH COOH

<

NO 2 NO2 3,5-ditert-butyl-4-nitrobenzoic acid 2,6-ditert-butyl-4-nitrobenzoic acid (I) (II) (II) is more acidic than (I). Because in (I) there is SIR. In fact, the presence of –NO group at δ 2 the para position w.r.t the –COOH group produces + charge on the ipso carbon(C1) (i.e para to the –NO2 group) which produces a strong –I effect to stabilise the conjugate base of the acid i.e Ar–COO–. Note that there is no resonance between benzene ring and –COO– group as, the latter is a strong electron donating group and moreover it is not lying in the same plane as of the benzene ring. The stabilisation is due to the indirect –M effect of –NO at the para-position δ 2 which produces + charge at C1. This, in turn, makes the p-nitrophenyl group a stronger –I group. Let me remind you that a –M group produces +δ charge at the two ortho positions and one para positions(three positions) w.r.t to that group, while a +M group produces –δ charge on the above δ mentioned positions. Had the –NO2 group been in the meta position w.r.t –COOH group, the + – charge would not have appeared on C1, in stead appeared on C2, C4 and C6 with respect to COO – i.e ortho/para to the –NO2 group occupying meta w.r.t COO . Thus, only –I effect of –NO2 would have come to force to make the m-nitrophenyl a less –I group than p-nitrophenyl group which δ – produces a clear-cut + charge on C1, which is adjacent to –COO . I think, this much will enough for your understanding.

But due to presence of two bulky tert-butyl groups at the ortho positions w.r.t –NO2 group in (I), the planarity at that portion is destroyed. That decreases the extent of resonance(–M effect of δ –NO2 group) and hence the magnitude of + charge on C1 becomes less. Thus thus the stabilisation to the –COO– becomes less. Let me give the RSs for a better clarity. I thought to give it later while dealing with aromatics, but i changed my mind to give now.

O O O O O O O O C C C C

N N O N N O O O O O O O

O O C +

+ +

- N O O Dr. S. S. Tripathy General Organic Chemistry-Part I 55

In (II) –NO2 group is free of SIR, as the bulky t-Bu groups are away from it. Their presence ortho to COO– has no impact on resonance, as benzene ring is not in resonance with COO–. Its presence ortho to –NO2 group would cause SIR as resonance is caused by –NO2 group and not by –COO–. 2.

NH 2 NH2

H3C CH3 > CH H3C 3 NO 2 NO2 3,5-dimethyl-4-nitroaniline 2,6-dimethyl-4-nitroaniline (I) (II) pKA 2.49 0.95

Electron withdrawing groups like –NO2, –CN, –CHO etc. at the ortho and para positions w.r.t a +M group like –NH2, –OH, –OR extends the conjugation. Thus the lone pair on N-atom is futher delocalised beyond the ring into the -NO2 group and thus reduces basicity further. Had the

–NO2 group lie in the meta position w.r.t –NH2 group, it would have delocalised the lone pair of N atom of –NH2 group by mere –I effect, which is less pronounced than –M effect produced at the o- and p- positions. We are deviating from the moot issue i.e SIR.

SIR is present in both (I) and (II). Since –NO2 is a bulkier group than –NH2 group, SIR is more pronounced in I. Thus the extent of electron delocalisation is decreased in (I) due to more pronounced SIR and thus the lone pair is more available on N atom of –NH2 group in (I). Thus (II) is much weaker compared to (I).

NH2 NH2 NH2 NH2

N N N O O N O O O O O O

+ NH2

- -

- N O O

Actually, the number of RSs should be 5 (five conujgating units including –NO2 group), i have shown four. The RS in which -ve charge will lie on para position w.r.t to –NH2 has not been shown. Just i have missed it and have no mood to redraw. Please do it for me. The delocalisation of lone pair is extended to –NO2 group and hence less available on NH2 group. Hence p- nitroaniline(pKA = 1.02) is less basic than aniline(pKA = 4.58). (Don’t poke your nose now to know why (II) is less basic than p-nitroaniline, although you can justify why (I) is more basic than p-nitroaniline by +I effects of Me– groups. Let us forget the the cause for the former for time being. I wish, i should not have given pKA value of p-nitroaniline !!!). Dr. S. S. Tripathy 56 General Organic Chemistry-Part I (3) Basicity of N-substituted anilines can also be explained by SIR.

Me Me Et Me Et Et tBu NH2 NH N NH N NH

pKA 4.58 4.85 5.06 5.11 6.56 7.1 If we take increase in +I effect of alkyl groups from left to right, then that would enhance +M effect of amino function and thus would reduce the basicity. In reality, it is just the opposite. This can be explained by SIR. The increase in the bulk of the alkyl group around the N-atom produces more SIR and hence the lone pair is less delocalised and so more available.

(B) Steric Effects in Chemical Reactions: Steric strain in a molecule or steric strain caused in the transition state(TS) in a reaction can very much affect both rate as well as course of reaction. Since we shall be discussing the mechanism of organic reactions in some details a bit later, we cannot now take up adequate examples to demonstrate this effect. (i) Steric Hindrance to Attaking species:

fast (I) CH3 CH2 Br + EtOH CH3 CH2 OEt + HBr

slow (II) CH3 CH CH2 Br + EtOH CH3 CH CH2 OEt + HBr

CH3 CH3

Ethyl bromide is solvolysed by EtOH much faster than isobutyl bromide. This because of steric hindrace offered by the i-Pr group at the site of nucleophilic attack in (II) compared to Me– group in (I). We shall later know that both are 10 alkyl halide and the substitution mechanism is

SN2(bimolecular nucleophilic substitution). For that the nucleophile has to attack from the rear side of the leaving group (–Br) and the reaction takes place in one step. Bulkier group will offer steric hindrance to the approach of the nucleophile in (II) and hence react slowly. More on this will be taken up later. (ii) Relief of Steric Strain in the Substrate Molecule:

(I) slower Me3C Cl + H2O Me3C OH + HCl

faster (II) Et3C Cl + H2O Et3C OH + HCl

0 Both are tert-(3 ) alkyl halides. But steric strain is more in Et3C–Cl than Me3C–Cl. Hence the former react faster to relieve of the strain. Just like you are more hungry than your friend and hence you will eat faster. In the same manner, the molecule having greater steric strain will like to relieve the strain faster than the one having lesser strain. We shall know later, that here the mechanism is SN1 which goes via the formation of carbocation intermediate, which are planar. But the substrate is tetrahedral and hence is at strain, but the intermediate carbocations are having much lesser steric strain. Hence the difference. (C) Stereoelectronic Effects in Chemical Reactions: Here, the steric factor is coupled with electronic factor, hence the name stereoelectronic effect. To demonstrate this, we shall take now only one example. It might be hard for you at this stage.

Dr. S. S. Tripathy General Organic Chemistry-Part I 57 But never mind. Read it.

Cl

H t-BuO ++t-BuOH Cl H fast H cis-4-tert-butyl-1-chlorocyclohexane 4-tert-butylcyclohexene

H H flipping t-BuO Cl (SLOW) H 4-tert-butylcyclohexene H Cl trans-4-tert-butyl-1-chlorocyclohexane (Unstable) + (1,3-diaxial interaction) + t-BuOH Cl

This elimination of HCl by use of a strong base t-BuO– (t-BuOK). The elimination mechanism + – is called E2, which demands that the two leaving groups (H and Cl in this case) should remain anti(dihedral angle of 1800) to each other in the TS for the elimination. This is called antiperiplanarity condition for the E2 mechanism(we shall study in some time). In the cis-isomer H and Cl are in the axial positions and hence the antiperiplanarity condition is met. For this reason, it eliminates in much faster rate to form the cyclohexene dertivative. However the trans isomer has to flip to the most unfavourable diaxial conformation to meet the antiperiplanarity condition. Since t-Bu group is very bulky and will produce huge 1,3-diaxial repulsion, if occupies axial position. Due to very high energy TS of this diaxial conformation, the trans isomer reacts with a much slower rate than the cis isomer. Note that both steric effect and electronic effect(electron displacement through bonds) are involved in this case. Hence it is called stereoelectronic effect. (Have i succeeded to convince you much ahead of its schedule in this e-book ???? )

FIELD EFFECTS:

Inductive Effect(I-effect) is always associated with Field Effect and the two effects are inseparable. However, for many molecules, when the polarity is small, contribution of Field effect is negligible. Lets now know what is Field Effect ? The polarisation of electron pair by permanent dipole or charge in space or through solvent molecules by electrostatic interactions is called Field Effect. If this polarization is induced through relaying effect n sigma bonds, it is called I-effect. I-effect is not dependent on the spatial distance of one pole(or dipole) on the other, it only counts the inervening sigma bonds between the –I group and the the group or atom to which the effect is expected to be observed. Just like, I -effect dies down after a few sigma bonds, Field effect also works in short distance in space and dies down at longer distances. So Field effect is a through-space effect while Inductive effect is through-bond effect. But the same I group produces both the effects. See the following example. Dr. S. S. Tripathy 58 General Organic Chemistry-Part I

- Field effect O + C CH3 other molecules H3N(CH2)n -I group + δ –NH3 grou; is a –I group, which produces greater electrophilicity(+ ) on the carbonyl carbon by a through-bond effect(–I effect). But the same group can produce a through-space effect on the carbonyl oxygen(electrostatic attraction), which also favours polarisation of the pi-bond of the carbonyl group. So both –I effect and Field effect are observed simultaneously and one compliments the other. In case, there is a full charge(not a fractional charge in neutral molecules) like the one given above, the Field effect is also appreciable to enhance the overall effect of polarization. Example: K A1 Look only to the K of the dicarboxylic acids given in the following table. A2

KA1 pKA 1 pKA2 ratio KA2

HOOC COOH 1.27 4.26 989 oxlaic acid 5.7 692 HOOC CH2 COOH 2.86 malonic acid 26.9 HOOC CH2 CH2 COOH 4.21 5.64 succninic acid 8.51 HOOC CH2 CH2 CH2 COOH 4.34 5.27 glutaric acid 4.41 5.28 7.41 HOOC (CH2)4 COOH adipic acid

K < K is always the case. To remove a second H+ ion from a –ve charged carboxylate ion A2 A1 is difficult and hence 2nd dissociation constant is always less than 1st dissociation constant. But K A1 as the chain is short eg oxalic acid, the K ratio is very high(989). To understand this see the A2 following acid dissociation equilibria.

+ Field effect - H O O KA1 HOOC (CH2)n COOH O C (CH2)n C O -H +I group KA2 -H

OOC (CH2)n COO Dr. S. S. Tripathy General Organic Chemistry-Part I 59 The first formed carboxylate ion (COO–) produces both +I effect and Field effect to make the dissocation more difficult. The attraction of –COO– to the H pole of the other –COOH makes it more difficult to be lost as free ion. So 2nd dissociation constant is much less than the 1st.

Only +I effect cannot explain the unexpectedly large ratio of the KA values in oxalic acid. As chain length increases, both +I and Field effects diminish and hence the ratio decreases drastically after succinic acid. Note that Field effect can operate both in presence of solvent(say water) or in empty space(in gaseou state).

Field Effect Cyclic compounds: In acyclic compounds, we have seen that I– and Field effects go hand in hand. For neutral molecules like R–X, the field effect may be insignificant, while in charged ions, the Field effect contributes appreciably. In certain cyclic compounds, certain property can only be explained through Field effect in isolation. Though I-effect is coexisting, but it is only through Field effect the difference can be explained. See the following example.

H Cl Cl H H Cl Cl H

COOH COOH

pKA = 5.67 pKA = 6.07

In the first acid, the two Cl- atoms are colser (cis isomer) to –COOH group and hence there is greater through-space electrostatic attraction between -δ of Cl atoms and +δ of H atom of

COOH. This reduces the ease of dissociation and hence the cis- acid is weaker(higer pKA value) than the trans- acid(given in the 2nd structure). I- effect wise, the number of sigma bond separation is same in both. So it is only by Field effect, we can explain the difference.

Dr. S. S. Tripathy