Alcohols : Dehydration reaction, reaction with phosphorus halides, ZnCl2/conc HCl,
Ethers : Preparation by Williamson�s Synthesis;
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Page # 2
1. NUCLEOPHILE & NUCLEOPHILICITY
1. NUCLEOPHILE : It is the e� rich species having atleast one lone pair of electrons. It can be neutralor �vely charged it is always a lewis base.
BASICITY : It is the tendency to donate e� pair to ion.All bases are nucleophiles, but all nucleophlies are not base all the time.
(i)
(ii)
1.1 NUCLEOPHILICITY :The tendency to give e� pair to an electron deficient carbon atom is defined as nucleophilicity.
(i) Criteria for Nucleophilicity :1. The factors which increases e� density at �donor atom increases nucleophilicity�.
2. The more polarisable donar atom is a better nucleophile. Therefore, large size of donor atomincreases nucleophilicity.
(ii) Periodicity :Nucleophilicity decreases from left to right in a period.
In a group, nucleophilicity increases from top to bottom due to increases in size of donor atom, butbasicity decreases from top to bottom.Acid strength : HI > HBr > HCl > HFBasic strength : F¯ > Cl� > Br� > I�
Nucleophilicity : F¯ < Cl� < Br� < I�
(iii) Steric effects on nucleophilicity
Stronger base, yet weakernucleophile cannot approachthe carbon atom so easily.
(iv) The effect of the solvent In polar protic solvent large nucleophiles are good, and the halide ionsshow the following order
In DMSO, the relative order of reactivity of halide ions is
> > >
Page # 3
This effect is related to the strength of the interaction between nucleophile and solvent molecules of polarprotic solvent forms hydrogen bond to nucleophiles in the following manner :
(v) Relative nucleophilicity in polar protic solvent
> > > > > > > H2O
(vi) Comparative chart
Nucleophilicity Basicity Remarks
1. CH3¯ > NH
2¯ > OH¯ > F¯ CH
3¯ > NH
2¯ > OH¯ > F¯ If donor atomis belong to
same period, nuclephilicityand basicity order is same
2. SiH3¯ > PH
2¯ > SH¯ > Cl¯ SiH
3¯ > PH
2¯ > SH¯ > Cl¯
3. F¯< Cl¯ < Br¯ < I¯ F¯> Cl¯ > Br¯ > I¯ In a group nucleophilicityincreases while basicitydecreases. on moving top tobottom.
4. OH¯ < SH¯ OH¯ > SH¯ , ,
5. RO¯ < RS¯ RO¯ > RS¯ , ,
6. RO¯ > HO¯ Same If donor atom is same,nucleophilicity and basicityhave same order
2. Leaving group Ability/Nucleofugality :The best leaving groups are those that become the most stable ion after they leave, because leaving groupgenerally leave as a negative ion, so those leaving group are good, which stabilise negative charge mosteffectively and weak base do this best, so weaker bases are always good leaving groups. A goodleaving group always stabilize the transition state and lowers its free energy of activation and there byincreases the rate of the reaction.(a) Order of leaving ability of halide ion
> > >
(b) Other good leaving groups are
(c) Strongly basic ions rarely act as leaving group
(strong base / poor leaving group)
(It is not a leaving group)
(d) The weaker bases are better leaving groups.
(e) The leaving group should have lower bond energy with carbon.
(f) Negative charge should be more stable either by dispersal or declocalization.
(g) Leaving group ability :
1. CH3¯ < NH
2¯ < OH¯ < F¯
2. R�COO¯ > PhO¯ > HO¯ > RO¯
3. SH¯ > OH¯
4. >
Page # 5
2.1. Types of solvents
(a) Non polar
(b) Polar (These solvents are of two type - polar protic and polar aprotic)
Nucleophilic substitution which involves two step process(a) First step : - Slow step involves ionisation (to form carbocation)
R�g R+ + g �
(b) Second step : - Fast attack of nucleophile on carbocation to result into product .R+ + Nu
� R�Nu
3.1 SN1 Reaction of alkyl halide
Mechanism :
)rds(stepSlow
halidealkylofIonisation
# Carbocation intermediate is formed so rearrangement is possible in SN
1 reaction.
Kinetics: Rate [Alkyl halide]# It is unimolecular, two step process.# It is first order reaction.# Rate of S
N1 reaction is independent of the concentration and reactivity of nucleophile.
Energetics of the SN1 :
Figure : Free energy diagram for the SN
1 reaction.
Stereochemistry of SN1 reactions :
In the SN
1 mechanism, the carbocation intermediate is sp2 hybridized and planar, A nucleophile canattack on the carbocation from either face, if reactant is chiral than after attack of nucleophile from bothfaces gives both enantiomers as the product, which is called racemization.
Mechanism of racemization (SN1
Ion-pair concept : - % inversion > % retentionSo 100 % racemisation is not occur
Page # 7
Factor's affecting the rates of SN1 / Reactivity order :
(i) The structure of the substrate : The Rds of the SN
1 reaction is ionization step, a carbocation is formin this step. This ionisation is strongly endothermic process, rate of S
N1 reaction depends strongly on
carbocation stability because carbocation is the intermediate of SN
1 reaction which determines theenergy of activation of the reaction.
SN1 reactivity : 3° > 2° > 1° > CH3 � X
(ii) Concentration and reactivity of the nucleophile The rate of SN
1 reactions are unaffected by theconcentration and nature of the nucleophile
(iii) Nature of nucleophile:- Weak, neutral, protic solvents# In S
N1 reaction, mostly the solvent functions as nucleophile with oxygen & nitrogen as donor atom. So
SN
1 reaction are termed as solvolysis reaction.H
2O hydrolysis
C2H
5OH ethanolysis
CH3COOH acetolysis
NH3 ammonolysis
SN
1 reaction is disfavoured by strong, anionic nucleophiles which attacks faster before ionisation takesplace leading to S
N2 mechanism.
R � X + H2O + OH2+ OH2+ OH2+ OH2+ OH2+ OH2+ OH2+ OH2+ OH2+ OH2+ OH2R+ OH2+ OH2+ OH2+ OH2 R � O � H
�
H
+R � O � H
�
H
+R � O � H
�
H
+R � O � H
�
H
+R � O � H
�
H
+R � O � H
�
H
+R � O � H
�
H
+R � O � H
�
H
+R � O � H
�
H
+R � O � H
�
H
+R � O � H
�
H
+R � O � H
�
H
+R � O � H
�
H
+R � O � H
�
H
+R � O � H
�
H
+ H�
R � OH + HX
(iv) Effect of the solvent : the ionizing ability of the solvent :Because to solvate cations and anions so effectively the use of a polar protic solvent will greatlyincrease the rate of ionization of an alkyl halide in any S
N1 reaction. It does this because solvation
stabilizes the transition state leading to the intermediate carbocation and halide ion more than it doesthe reactant, thus the energy of activation is lower.
R � X (Solvolysis)
Solvated ions
(v) The nature of the leaving group In the SN
1 reaction the leaving group begins to acquire a negativecharge as the transition state is reached stabilisation of this developing negative charge at the leavinggroup stabilizes the transition state and ; this lowers the free energy of activation and thereby increasesthe rate of reaction.
Note : Only AgF is soluble among all silver halides To prepare alkyl flouride
6 h/Br2
OH/AgF 2
7. acetoneOH2
shiftH
8.
9.
10.
11.
12. Ag/MeOH
[Diastereomers](Not recemic mix [] 0)
Page # 9
13.
Q.1 Give the solvolysis products when each compound is heated in ethanol
(a) (b) (c) (d)
Sol. (a) (b) (c) (d)
Q.2 Predict the compound in each pair that will undergo solvolysis (in aqueous ethanol) more rapidly.
Sol. (a) II > I (b) II > I (c) I > II(d) II > I (e) II > I
Q.3 The rate of SN1 reaction is fastest with
(A) (B)
(C) (D)
Ans. A > B > D > C
Page # 10
SN1� (� - Prime)
The substitution of alkylic system under SN1 conditions proceeds with rearrangement.
R�CH=CH�CH2�X
�X� R �CH=CH� 2HC
R� HC
�CH=CH2
R�CH=CH�CH2�Y
3.2 SN1 Reaction of Alcohols(A) Reaction with hydrogen halides
A common method is to treat the alcohol with a hydrohalic acid, usually HI or HBr. These acids areused to convert alcohols to the corresponding alkyl halides.
(i) In acidic solution, an alcohol is in equilibrium with its protonated form. Protonation converts the
hydroxy group from a poor leaving group to a good leaving group (H2O). If the alcohol is
protonated all the usual substitution and elimination reactions are feasible, depending on the struc-ture (1°, 2°, 3°) of the alcohol.
(ii) Halides are anions of strong acids, so they are weak bases. Solutions of HBr and HI contain
nucleophilic and ions.
(iii) Concentrated hydrobromic acid rapidly converts t-Butyl alcohol to t-Butyl bromide. The strong acidprotonates the hydroxyl group, converting it to a good leaving group. The hindered tertiary carbonatom cannot undergo S
N2 displacement, but it can ionise to a tertiary carbocation. Attack by
bromide ion gives the alkyl bromide. The mechanism is similar to other SN1 mechanism.
(iv) 1-Butanol reacts with sodium bromide in concentrated sulfuric acid to give 1-Bromobutane by an SN2
displacement.
oltanbu1OHCH)CH(CH 2223
42SOH,NaBr
%)90(etanbromobu1
BrCH)CH(CH 2223
Protonation converts the hydroxy group to a good leaving group, but ionization to a primary carbocationis unfavourable. The protonated unbranched primary alcohol is well suited for the S
N2 displacement.
(v) Secondary alcohols also react with HBr to form alkyl bromides usually by the SN1 mechanism.
e.g. HBr
(vi) HCl (Hydrochloric acid) reacts with alcohols in much the same way that as the hydrobromic acid.
(vii) Chloride ion is a weaker nucleophlile than bromide ion because it is smaller and less polarizable.Lewis acid, such as ZnCl
2, is sometimes necessary to promote the reaction of HCl with primary and
secondary alcohols.
Lucas Reagent
(i) A mixture of concentrated hydrochloric acid and anhydrous zinc chloride is called the Lucas reagent.
(ii) Whether an alcohol is primary, secondary or tertiary i.e. identify by the Lucas test, which is basedupon the difference in reactivity of the three classes of alcohol towards hydrogen halides.
(iii) Alcohol (of not more than six carbons in their molecule) are soluble in the Lucas reagent. Thecorresponding alkyl chlorides are insoluble.
Page # 11
(iv) Formation of a chloride from an alcohol is indicated by the cloudiness that appears when the chlorideseparates from the solution hence, the time required for cloudiness to appear is a measure of thereactivity of the alcohol.
(v) A tertiary alcohol reacts immediately with the Lucas reagent, a secondary alcohol reacts within fiveminutes and a primary alcohol does not react appreciably at room temperature.
e.g.
OH|
CHCHCHCHCH 3223 HCl/ZnCl.anhy 2
entaChloropen3Cl|
CHCHCHCHCH 3223
Mechanism :
R �OH 2HOR
OH� 2
R R � X
Reactivity of HX : HI > HBr > HCl
Reactivity of ROH : allyl benzyl > 3° > 2° > 1°
e.g.
alcoholIsopropylOH|CHCHCH 33
bromideIsopropylBr|CHCHCH 33
e.g.
3
23
3
CH|
OH�CHCCH|
CH
Br|
CH�CHCCH|
CH
323
3
Example :
Ex.1
Ex.2
Page # 12
Ex.3 CH3 � CH = CH � CH
2OH
Ex.4 HBr
Ex.5 IH
Ex.6 Why is ZnCl2 (Lewis acid) required with HCl in its reaction with 1° and 2° alcohol. Where as reaction with HBr
proceeds without any Lewis acid.
Sol. Because the chloride ion is a weaker nucleophile than bromide or iodide ions. HCl does not react with 1° or
2° alcohols unless zinc chloride or some similar Lewis acid is added to the reaction mixture as well. ZnCl2
is a good Lewis acid, forms a complex with alcohol through association with an unshared pair of electrons onthe oxygen atom. This provides a better leaving group for the reaction than H
2O.
Ex.7 Make distinction between following pairs of substances by using Lucas reagent
Ans. (a) II > I (b) II > I (c) II > I
3.3 SN1 Reactions of Ethers(A) Reaction with HX
Ethers are unreactive towards most bases, but they can react under acidic conditions. A protonatedether can undergo substitution or elimination with the expulsion of an alcohol. Ethers react with conc.
HBr and HI because these reagents are sufficiently acidic to protonate the ether, while bromide iodide
Page # 13
are good nucleophiles for the substitution.If R or R� is 3º then mechanism will be SN1 otherwise SN2 .
Alcohols : Dehydration reaction, reaction with phosphorus halides, ZnCl2/conc HCl,
Ethers : Preparation by Williamson�s Synthesis;
Page # 15
4. NUCLEOPHILIC SUBSTITUTION REACTION (SN2)
4.1 SN2 Reaction of alkyl halide :
Mechanism :
+
# No intermediates are formed in the SN
2 reaction, the reaction proceeds through the formation ofan unstable arrangment of atoms or group called transition state.
Kinetics :rate [alkyl halide] [nucleophile]rate = k[alkyl halide] [nucleophile]# It is bimolecular, one step concerted process# It is second order reaction because in the RDS both species are involved
Energetics of the reaction :
Figure : A free energy diagrams for SN
2 reaction
Stereochemistry of SN2 reactions :
As we seen earlier, in an SN
2 mechanism the nucleophile attacks from the back side, that is from the
side directly opposite to the leaving group. This mode of attack causes an inversion of configurationat the carbon atom. This inversion is also known as Walden inversion.
Inversion
Factor's affecting the rate of SN2 reaction/Reactivity order
(i) Effect of the structure of the substrate Order of reactivity in S
N2 reaction : � CH
3 > 1° > 2° >> 3° (unreactive)
The important reason behind this order of reactivity is a steric effect. Very large and bulky groups canoften hinder the formation of the required transition state and crowding raises the energy of the transitionstate and slows down reaction.(ii) Concentration and reactivity of the nucleophile
As nucleophilicity of nucleophile increases rate of SN
2 increases.� Anionic nucleophiles mostly give S
N2 reaction
Page # 16
� A stronger nucleophile attacks upon -carbon with faster rate than the rate of departing of leavinggroup. R� > NH
2� > OH� > F�
RO� > ROHNaOH > H
2O
NH3 > H
2O
Table :
(iii) The effect of the solvent: Polar aprotic solvent have crowded positive centre, so they do not solvatethe anion appreciably therefore the rate of S
N2 reactions increased when they are carried out in polar
aprotic solvent.(iv) The nature of the leaving group Weaker bases are good leaving groups. A good leaving group alwaysstabilize the transition state and lowers its free energy of activation and thereby increases the rate ofthe reaction. Order of leaving ability of halide ion F¯ < Cl¯ < Br¯ < I¯
Examples :
Ex.1 CH3�Cl
enucleophilstrong)OH(:
KOH.aq
CH3�OH + Cl�
Ex.2 CH3�CH�Cl
DMSOKOH CH3�CH
2�OH + Cl�
Ex.3 CH3�CH
2�CH
2�Br
DMFNaOH CH3�CH
2�CH
2�OH + Br�
Ex.4 (CH3)
2CHCH
2CH
2 � Br
OHKOH
2
(CH3)
2CHCH
2CH
2 � OH
Ex.5 MeOH Na
BrPhCH2 CH � O � CH2 3
Benzylmethyl ether
Ex.6
Page # 17
Ex.7. DMSOKOH
2° RX, [D] 2° ROH, [L]
[] 0° = x° (Assumed) [] 0 �x° (optically pure only one enantiomer is obtained)
Ex.8. DMSOKOH
Ex.9. KCN
Only one optically active product (Walden inversion at carbon 2)Replace nucleophile with halogen directly and make any 1 (only1) change on the -chiral carbon.
General reaction R � Cl + NaI Acetone R � I + NaCl ppt in acetone
R � Br + NaI Acetone R � I + NaBr ppt in acetone
Note: In acetone, NaI is soluble / ionised but NaCl/NaBr are insoluble
For I � exchange NaI/acetone is used so that chlorides and bromides get precipitate out
Ex.10.
C H(reactant)[ ] = xº
6 13
CH3
IH + NaI*
Transition stateC H
(product)[ ] = �xº
6 13
CH3
H + NaII
Polarimeter can detect difference between H and D, but not isotopes of higher elements.For polarimeter reactants and products are mirror image in the above example.
(1) In this reaction, the nucleophile and the LG are the same species (I�).
(2) The reaction is an equilibrium reaction and at equilibrium rate of forward reaction = rate of backwardreaction.
(3) In this reaction the optically pure reactant loses its optical activity and net result is a racemicmixture.
(4) Since -Nu:-Nu:-Nu:-Nu:-Nu:-Nu:-Nu:-Nu:-Nu:-Nu:-Nu:-Nu:-Nu:-Nu:-Nu: and LG are same species, so the reactant and product are enantiomers. Although it isan S
N2 reaction, but racemisation shows there is complete inversion of configuration in forward reaction.
Page # 18
Q.1 What will be the retationship between rate of I* exchange and rate of racemisation.Sol. 2 × Rate of I* exchange = Rate of racemisation
or, Rate of Racemisation = 2 × Rate of reaction.
Q.2 Complete the following reactions with mechanism
?
Sol. Na
Q.3. + CH3I .eq1
KOH ?
Sol.
Q.4. + Ph � CH2Cl
Sol. is present in excess and is stronger nucleophile than so product is Ph � CH2 � OEt
Q.5. CH3 � C CH
Na X I23 CHCH
Y
Sol.
Y
CHCHCCCH 323
Q.6. + salt
Sol.
Q.7. In the given reaction, CH3CH
2 � X + CH
3SNa
The fastest reaction occurs when �X� is -
(A) � OH (B) � F (C) � OCOCF3
(D) OCOCH3
Ans. CQ.8. Correct decreasing order of reactivity towards S
(A) IV > I > II > III (B) III > II > I > IV (C) IV > I > III > II (D) II > I > IV > IIIAns. B
Page # 19
Q.9. Draw a fischer projection for the product of the following SN
2 reaction
(a) Acetone/NaI (b)
Sol. (a) (b)
Intramolecular SN2 reactions
rate of intramolecular reaction > intermolecular reaction
(i) NaOH
(ii) ether
Na (Wurtz reaction)
reactionS
rramoleculaint
2N
(iii) Na
(iv) Na
(v) ether/Mg
(vi) Write mechanisms that account for the product of the following reactions :
NH2 � CH
2 � CH
2 � CH
2 � CH
2 � Br
Sol.
Page # 20
SN2 MechanismNucleophilic substitution on allylic system may proceed also via SN2 mechanism, in which the rearrange-ment does not take place. By the same concepts allylic rearrangement may proceed via an SN2 likemechanism called the SN2� mechanism.
Conditions for SN2�(1) A nucleophilic attack on the -carbon(2) A Concerted movement of three e� pair occurs.
The reaction is particularly susceptible to steric hinderance especially at the -C.Substrates with C=C�CH
2�X shows a strong preference for SN2 while sustrates of the type
�C=C�CR2�X favours SN2� mechanism.
Ex. OH
Ex. SH
The SN21 mechanism has also been demonstrated in propargyl systems, which results in an allene.
Ph�CC�CH2�OTs + CH
3MgBr .
Comparision between SN1 / SN
2 reaction :
Characteristics SN2 SN
1
1. Energetic
2. Kinetics r [RX] [NU:] r [RX]
3. Stereochemistry inversion racemisation
4. Rearrangement not possible possible
5. Activation energy 2NSEa > 1N
SEa less
6. Nature of R � X Me � X > R CH2 X > R2 CH X > R3CX R3CX > R2CHX > RCH2X > CH3X
7. Nucleophile strong anionic Weak neutral
R� > NH2� > OR� > OH� H
2O > MeOH > EtOH > NH
3
8. Leaving group � > Br� > Cl� > F� (same)
9. Solvent Polar aprotic Polar protic
10. Temperature High Low
Page # 21
Example :
1.
+
2.
3.
4.
4.2 SN2 Reaction of Alcohol(A) Reaction with HX : The protonated unbranched primary alcohol is well suited for the S
N2 reaction.
Mechanism :
R �OH 2HOR
X
R � X + H2O
e.galcoholPentyln
OHCHCHCHCHCH 22223
chloridePentyln
ClCHCHCHCHCH 22223
Page # 22
(B) Reaction with phosphorus trihalidesSeveral phosphorus halides are useful for converting alcohols to alkyl halides. PBr
3, PCl
3, & PCl
5 work
well and are commercially available.Phosphorus halides produce good yields of most primary and secondary alkyl halides, but none workswell with tertiary. alcohols. The two phosphorus halides used most often are PBr
3 and the P4/I2 combi-
nation.
3R � OH + PX3 3R � X + H
3PO
3
Mechanism :
Step : 1
Step : 2 RCH2X+ HOPX
2
e.g.oltanbu1Methyl2
OH�CH�CH�CH�CH|
CH
223
3
3PBr etanbromobu1Methyl2
Br�CH�CH�CH�CH|
CH
223
3
e.g.alcoholEthyl
OHCHCH 23 2P I
iodideEthylCHCH 23 I
e.g.
e.g.
(C) Reaction with thionyl chloride in presence of pyridineThionyl chloride (SOCl
2) is often the best reagent for converting an alcohol to an alkyl chloride. The by
products (gaseous SO2 and HCl) leave the reaction mixture and ensure that there can be no reverse
reaction.
R � OH + ClSCl||O
Pyridine
Heat R � Cl + SO
2 + HCl
Mechanism :
H�
R � O � SO
Cl
:..
.. ..
..
Chlorosulphite ester
+ HCl
R � Cl + SO2
In the first step, the nonbonding electrons of the hydroxy oxygen atom attack the electrophilic sulphuratom of thionyl chloride. A chloride ion is expelled a proton and gives test of chloro sulphite ester.Second step is an S
N2 mechanism
Page # 23
e.g. Py
SOCl2
(D) Reaction with thionyl chlorideROH + SOCl
2 RCl + SO
2 + HCl
In this mechanism an internal nucleophile attacks from the same side of leaving group , means retensionof configuration . It is an S
Ni mechanism , where i means internal
Mechanism :
H�
R � O � SO
Cl
:..
.. ..
..
Chlorosulphite ester
+ HCl
R � Cl + SO2
e.g. C
ClH
CH (CH ) CH3 2 4 2 CH3
2-Chlorooctane 84%
(R)
4.3 SN2 Reaction of Ether(A) Reaction with HX
Ethers are unreactive toward most bases, but they can react under acidic conditions. A protonated ethercan undergo substitution reaction. Ether react with conc. HBr and HI because these reagents aresufficiently acidic to protonate the ether. If R or R� is 3º then mechanism will be S
N1 otherwise S
N2.
Mechanism :
+ halidealkylRX +
HX X � R + X � R
e.g. (i) CH3CH
2OCH
2CH
3
excess
HBr 2CH
3 � CH
2Br
Mech.
bromideethylH|
HCCH|Br
3 +
CH3CH
2Br
Ex.1 CH3CH
2 � O � CH
3
H
Ex.2 HBrexcess
Page # 24
Ex.3
Ex.4 CH3 �
��
CH3
HC �
CH3
HC �
CH3
HC �
CH3
HC �
CH3
HC �
CH3
HC �
CH3
HC �
CH3
HC �
CH3
HC �
CH3
HC �
CH3
HC �
CH3
HC �
CH3
HC �
CH3
HC �
CH3
HC � O � CH
2 � CH
3
HBrCH
3 �
��
CH3
HC �
CH3
HC �
CH3
HC �
CH3
HC �
CH3
HC �
CH3
HC �
CH3
HC �
CH3
HC �
CH3
HC �
CH3
HC �
CH3
HC �
CH3
HC �
CH3
HC �
CH3
HC �
CH3
HC � OH + CH
3 � CH
2 � Br
major)S( 2
N
Ex.5 Ph HO
Me
DEt
Me
)S(
HBr1
N
HOH
Me
D(Retention)
+ Ph
Et(Racemisation)
Me
Br + Ph
Et
Me
Br
Ex.6 1
2 3
4OOOOOOOOOOOOOOO )S(
H1
N
I
1
2
3
4
OHIIIIIIIIIIIIIII
4.4 SN Reaction of EpoxideEpoxides are much more reactive than ether because of angle strain in three membered ring thereforeepoxide readily undergo nucleophilic substitution reaction.
(a) In basic medium mechanism is SN2. Nucleophile atacks on less hindered carbon.
Mechanism :
O|
CH�CH�R|Nu
2 H
OH|
CH�CH�R|Nu
2
e.g.
(b) In acidic medium mechanism is SN1 type. Nucleophilic attacks on more substituted carbon.
Mechanism :
H
OH|CH�CH�R
|Nu
2
e.g.
H
OH 182
e.g.
Page # 25
5. ELIMINATION REACTIONSIn an elimination reaction two atoms or groups (YZ) are removed from the substrate and generallyresulting into formation of bond.
ZY||CC||
YZinationlimE
-elimination : When two groups are lost from the same carbon atom to give a carbene (or nitrene).This is also called 1�1 elimination.
XY� C�C:
-elimination : When two groups are lost from adjacent atoms so that a bond is formed. This is alsocalled 1�2 elimination.
C=C
�elimination : It is also called 1�3 elimination, In this a three membered ring is formed.
E1 Reaction :Proton and leaving group depart in two different step.
(a) First step : - Slow step involves ionisation to form carbocation(b) Second step : Abstraction of proton
5.1 E1 Reaction of alkyl halide : Mechanism :
Step 1 : Formation of the carbocation (RDS)
Step 2 : Base ( ) abstracts a proton (fast)
+ B � H
# In the second step, a base abstracts a proton from the carbon atom adjacent to the carbocation, andforms alkene.# Reaction intermediate is carbocation, so rearrangment is possible
Kinetics Rate [Alkylhalide]Rate = k [Alkylhalide]# It is unimolecular, two step process.
# It is a first order reaction.
Page # 26
Energetics The free energy diagram for the E1 reaction is similar to that for the S
N1 reaction.
Reactivity Order :# Similar to S
N1 becuase Carbocation Intermediate is formed in the rds step.
SN1 vs E1 :In case of alkyl halide S
N1
product is always more than E1 product
Example :
Ex.1
Br|
CHCCHCH|CH
323
3
Ex.2 + and
% yield I > II > III [JEE 2000]
Note : The minor product formed before the carbocation rearrangement is not consider.
Ex.3 Propose mechanisms to account for the four products shown below
,OHCH3 + + +
Sol. OHCH3
or
Page # 27
In the above example : SN1 > E1
# Et � OH is not a stronge base, not strong enough to break C-H bond and hence attack at positive
charge site.# In such reactions, S
N1 is major and E1 minor so, alkenes are not prepared by this method. water or
MeOH do not cause E1 (very weak base)
Ex.4 (X) + (Y) (W) + (Z)
+ve iodoform test given by both W & Z.
Sol. Rearranged Carbocation :
Y (d/) mixture of
X
and
5.2 E1 Reaction of AlcoholDehydration requires an acidic catalyst to protonate the hydroxyl group of the alcohol and convert it toa good leaving group. Loss of water, followed by loss of proton, gives the alkene. An equilibrium isestablished between reactants and products. For E1 mechanism reagents are (i) H
3PO
4/
(ii) H2SO
4 / 160º
OHH||CC||
acid CC
|| + H
2O (Rearrangement may occur)
Mechanism :
Step 1 :
Step 2 : +
Step 3 +
Page # 28
RemarksIn first step, an acid-base reaction a proton is rapidly transferred from the acid to one of the unsharedelecton pairs of the alcohol.In second step the carbon oxygen bond breaks. The leaving group is a water molecule :Finally,in third step the carbocation transfers a proton to a molecule of water. The result is the formationof a hydronium ion and an alkene.
Reactivity of ROH : 3° > 2° > 1°
Examples
Ex.1
CH OH2
42SOH.Conc
CH2
( )IMinor
+
Ex.2
Ex.3
Ex.4
Ex.5 + +
Ex.6
Ex.7
Ex.8
Ex.9 ,42SOH Ex.10
Page # 29
Pinacol-Pinacolone rearrangement
Mechanism
Examples :
Ex.1 /SOH 42
Ex.2 /SOH 42
Ex.3 + Ex.4
5.3 E1 Reaction of Ether :Elimination is not a favourable reaction for ether, but however few reactions have been observed.E1 Elimination takes place via formation of stable carbocation.Ether undergoes dehydration reaction in the presence of conc. H
2SO
4 /
e.g.
/SOH.Conc 42
Ethers dissolve in concentrated solutions of strong inorganic acids to from oxonium salts, i.e. ether behaveas bronsted Lowry bases.
R2O + H
2SO
4
-(R � O � R)
|H
+HSO4
R � OH +
sulphatehydrogenalkyl
OHSOOR 2
Ex.1 3223 CHCH�O�CHCH H
Ex.2 1
2 3
4OOOOOOOOOOOOOOO
42SOH
Page # 30
6. ELIMINATION REACTION (E2)
6.1 E2 Reaction of alkyl halide :Dehydrohalogenation is the elimination of a hydrogen and a halogen from an alkyl halide to form analkene. Dehydrohalogenation can take place by E1
and E2 mechanism.
Reagents : -(i) Hot alcoholic solution of KOH or EtO¯ / EtOH (ii) NaNH
2(iii) t-BuO¯
K in t-BuOH
Mechanism :
+ BH
Kinetics :
Rate [R � X] [Base] ; Rate = k [R � X] [ ]# This is a single step, bimolecular reaction
# It is a second order reaction
# Rearrangment is not possible
# For the lower energy of activation, transition state must be stable
# E2 follows a concerted mechanism
# The orientation of proton & leaving group should be antiperiplanar.# Here � H is eliminated by base hence called elimination
Saytzeff rule (Positional orientation of elimination) : In most E1 and E2 eliminations where there are two or more possible elimination products, the productwith the most highly substituted double bond will predominate. This is called the saytzeff or zaitsev rule.
Energetics : P.E. diagram for dehydrohalogenation of 2-bromo-2-methylbutane.
Reactivity order:R � I > R � Br > R � Cl > R � F
Page # 31
Examples :
e.g. +
e.g.
3
3
3
CH|
BrCCH|
CH
+ + H2O +
Formation of the Hoffmann productBulky bases can also accomplish dehydrohalogenations that do not follow the saytzeff rule. Due tosteric hindrance, a bulky base abstracts a less hindered proton, often the one that leads to formationof the least substituted product, called the Hoffmann product.
HBrH|||CHCCCH
||CHH
23
3
+
+
Stereochemistry of E2 Reaction :
1. It is a stereospecific reaction.
2. In the T.S., the L.G. and hydrogen are anti-parallel (or, anti-periplanar) to each other.
3. In the anti conformation, the T.S. is most stable due to minimum electronic repulsion.
4. So the product alkene of E2 reaction has one of the two possible orientations (i.e., either cis or trans)
5. Stereospecificity is observed only when one stereoisomer of reactant R � X is used.
6. Stereospecific reaction means the one stereoisomer gives one stereoisomer as a product
7. In the T.S., 5 atoms lie in the same plane ( , � H, � C, -C, g.)
Plane containing 5 atoms. T.S. (E2 reaction)
HCH3H
Br
PhPh
H
CH3
H
Br
Ph
Ph
Base
Ph H
PhCH3
Ph Ph
CH3
H
Trans
Examples :
Page # 32
Ex.1
Ex.2
Ex.3 KOH.Alc No. reaction
Ex.4 +
Ex.5 Ex.6 KOH.Alc
Ex.7 KOH.Alc
Ex.8
H
Ex.9
Page # 33
Ex.10
Comparison of E1 and E2 elimination:
Promoting factors E1 E2
(i) Base Weak base Strong base required
(ii) Solvent Good ionizing solvent Wide variety of solvent
(iii) Substrate 3° > 2° 3° > 2° > 1°
(iii) Leaving group Better one required Better one required
Characteristics
(i) Kinetics K [R � X] Ist order K [R � X] [Base] IIst order
(ii) Orientation Saytzeff alkene Saytzeff alkene
(iii) StereochemistryNo special geometryis required
transition statemust be co-planar
E1: rds1
:X
2
H
R�CH=CH2
E2: 1
R�CH=CH2
6.2 Elimination of alcohol :Reagent : Al
2O
3, P
2O
5, ThO
2
Cyclic Transition state is formed and rearrangement is not possible
Ex.1
Ex.2
Page # 34
7. E1cB Reaction
E1cB Reaction (Unimolecular conjugate base reaction)
In the E1cB, H leaves first and then the X. This is a two step process, the intermediate is a carbanion.
Mechanism :
Step - I : The removal of a proton
)H( by a base, generating a carbanion
||XCC
||H
(Conjugate base)
Step - II : Carbanion looses a leaving group to form alkene
||�CC�
Remark :(i) The strong base abstracts B � H (Significantly acidic) in 1st fast rev. step. As a result a carbanion intermediate (cb) is formed.(ii) In the 2nd slow step the leaving group is eliminated.
(iii) molecularity = 1, order = 1.(iv) Elcb is unimol . 1st order wrt. cb.Overall order = 2
Kinetics :
Rate
Evidence :
A : When the rxn is conducted in and a sample of rxn mixture is tested after some timeinterval, D - exchange is observed at � c.
(C � D is found)
R : It indicates that a carbanion intermediate is formed and first step is rev.
Factor which make � H significantly acidic
(a) When the leaving group is strongly electronegative (i.e. exerts strong - effect on � H)
F,
(b) Presence of EWG (� m) at � c
(c) poor l.g. favours E1cB
Note: if EWG is attached to � c,
then X can be Cl, Br, I, F, OH, OR, 3RN
, 2RS
Regioselectivity in E1cB (Hofmann elimination)
Ex.1
Page # 35
Ex.2
Ex. 3 R2C=O
Ex.4
Note :
Hofmann Elimination in Quaternary Ammonium Salts :
In Hoffmann degradation of quaternary ammonium salts, Hofmann alkene [less substiuted alkene] is formedas major product
Ex.5 CH2 = CH
2 + CH
3
Ex.6
/AgOH.2
CH.1 3 excessI
Ex.7
/AgOH.2
CH.1 3 excessI
Ex. 8
Ex.9
Page # 36
Faculty Remark
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