Session : 2012-13
ORGANIC CHEMISTRY
TOPIC : HALOALKANES & HALOARENES
CONTENTS :
1 Nucleophile
2. Leaving Group
3. Nucleophilic substitution (SN1) of RX. ROH, ROR
(i)
(ii)
1.1 NUCLEOPHILICITY :
The tendency to give e pair to an electron deficient carbon atom is defined as nucleophilicity.
In a group, nucleophilicity increases from top to bottom due to increases in size of donor atom, but
basicity decreases from top to bottom.
Acid strength : HI > HBr > HCl > HF
Basic strength : F > Cl > Br > I
Nucleophilicity : F < Cl < Br < I
(iv) The effect of the solvent In polar protic solvent large nucleophiles are good, and the halide ions
show the following order
Page # 2
This effect is related to the strength of the interaction between nucleophile and solvent molecules of polar
protic solvent forms hydrogen bond to nucleophiles in the following manner :
2. SiH3 > PH2 > SH > Cl SiH3 > PH2 > SH > Cl
,,
5. RO < RS RO > RS
,,
8. > Same
Page # 3
2. LEAVING GROUP ABILITY
(e) The leaving group should have lower bond energy with carbon.
3. SH > OH
4. >
Page # 4
2.1. Types of solvents
(a) Non polar
(b) Polar (These solvents are of two type - polar protic and polar aprotic)
Solvents Polar Protic Aprotic
1. H2O
2. CH3OH
3. CH3CH2OH
4. HCOOH
5. CH3COOH
6. NH3
7.
11.
12.
13. CCCCCC
Page # 5
3. NUCLEOPHILIC SUBSTITUTION REACTION
Ionisation of
alkyl halide
Slow step (rds)
H
(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 greatly
increase the rate of ionization of an alkyl halide in any SN1 reaction. It does this because solvation
stabilizes the transition state leading to the intermediate carbocation and halide ion more than it does
the reactant, thus the energy of activation is lower.
R X (Solvolysis)
Solvated ions
(v) The nature of the leaving group In the SN1 reaction the leaving group begins to acquire a negative
charge as the transition state is reached stabilisation of this developing negative charge at the leaving
group stabilizes the transition state and ; this lowers the free energy of activation and thereby increases
the rate of reaction.
Examples :
1. H2 O acetone
+ HBr (3 alkyl halide hence no SN2 reaction)
2. H O / Ag + AgI
2
3. CH OH / Ag
3 (carbocation rearrangement)
Page # 7
4.
6 Br2 / h AgF / H2 O
7. 2 H O acetone H shift
8.
9.
10.
11.
12. MeOH / Ag
Page # 8
13.
Q.1 Give the solvolysis products when each compound is heated in ethanol
Q.2 Predict the compound in each pair that will undergo solvolysis (in aqueous ethanol) more rapidly.
(A) (B)
(C) (D)
Ans. A>B>D>C
Page # 9
SN1 ( - Prime)
The substitution of alkylic system under SN1 conditions proceeds with rearrangement.
X
RCH=CHCH2X R CH=CH C H2 R C H CH=CH2
RCH=CHCH2Y
Protonation converts the hydroxy group to a good leaving group, but ionization to a primary carbocation
is unfavourable. The protonated unbranched primary alcohol is well suited for the SN2 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 ZnCl2, 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 based
upon 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. The
corresponding alkyl chlorides are insoluble.
Page # 10
(iv) Formation of a chloride from an alcohol is indicated by the cloudiness that appears when the chloride
separates from the solution hence, the time required for cloudiness to appear is a measure of the
reactivity of the alcohol.
(v) A tertiary alcohol reacts immediately with the Lucas reagent, a secondary alcohol reacts within five
minutes and a primary alcohol does not react appreciably at room temperature.
CH3 CHCH3
e.g. CH3 CHCH3 |
| Br
OH Isopropyl bromide
Isopropyl alcohol
CH3 CH3
| |
e.g. CH3 C CH2 OH CH3 C CH2 CH3
| |
CH3 Br
Example :
Ex.1
Ex.2
Page # 11
Ex.3 CH3 CH = CH CH2OH
Ex.4 HBr
Ex.5 HI
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 on
the oxygen atom. This provides a better leaving group for the reaction than H2O.
Ex.7 Make distinction between following pairs of substances by using Lucas reagent
Page # 12
are good nucleophiles for the substitution.
If R or R is 3 then mechanism will be SN1 otherwise SN2 .
Mechanism :
X
R O R` (3) R` X
ROH
HCl
e.g. (CH3)3COC(CH3)3 (CH3 )3 C O C(CH3 )3
|
H
(CH3 )3 C + (CH3)3COH
(CH3)3CCl
HBr (1eq.)
e.g.
HBr (1eq.)
e.g.
H
ROR` e.g.
H O
3
H O
e.g. 3
Page # 13
LECTURE NOTES
Session - 2009-10
ORGANIC CHEMISTRY
TOPIC : REACTION MECHANISM
CONTENTS :
4. Nucleophilic substitution (SN2) /RX. ROH, ROR
5. Elimination Reaction (E1)/ RX. ROH, ROR
6. Elimination Reaction (E2)/ RX. ROH, ROR
7. Elimination Reaction (E1cB)
Mechanism :
# No intermediates are formed in the SN2 reaction, the reaction proceeds through the formation of
an 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
Inversion
Table :
(iii) The effect of the solvent: Polar aprotic solvent have crowded positive centre, so they do not solvate
the anion appreciably therefore the rate of SN2 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 always
stabilize the transition state and lowers its free energy of activation and thereby increases the rate of
the reaction. Order of leaving ability of halide ion F < Cl < Br < I
Examples :
aq.KOH
Ex.1 CH3Cl
CH3OH + Cl
(:OH ) strong nucleophil e
KOH
Ex.4 (CH3)2CHCH2CH2 Br
(CH3)2CHCH2CH2 OH
H2O
Ex.6
Page # 16
KOH DMSO
Ex.7.
KOH DMSO
Ex.8.
KCN
Ex.9.
CH3 CH3
Ex.10. H I + NaI* I H + NaI
C6H13 C6H13
(reactant) Transition state (product)
[] = x [] = x
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 backward
reaction.
(3) In this reaction the optically pure reactant loses its optical activity and net result is a racemic
mixture.
(4) Since Nu:- and LG are same species, so the reactant and product are enantiomers. Although it is
an SN2 reaction, but racemisation shows there is complete inversion of configuration in forward reaction.
Page # 17
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
KOH
Q.3. + CH3I ?
1 eq.
Sol.
Q.4. + Ph CH2Cl
Sol. is present in excess and is stronger nucleophile than so product is Ph CH2 OEt
Na CH3 CH2 I
Q.5. CH3 C CH X Y
Q.6. + salt
Sol.
Page # 18
Q.9. Draw a fischer projection for the product of the following SN2 reaction
(i) NaOH
Na
(ii)
ether
(Wurtz reaction)
int ramolecula r
S 2 reaction
N
(iii) Na
(iv) Na
(v) Mg / ether
(vi) Write mechanisms that account for the product of the following reactions :
Sol.
Page # 19
SN2 Mechanism
Nucleophilic 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 like
mechanism called the SN2 mechanism.
Conditions for SN2
(1) A nucleophilic attack on the -carbon
(2) A Concerted movement of three e pair occurs.
OH
Ex.
Ex. SH
The SN21 mechanism has also been demonstrated in propargyl systems, which results in an allene.
PhCCCH2OTs + CH3MgBr .
1. Energetic
6. Nature of R X Me X > R CH2 X > R2 CH X > R3CX R3CX > R2CHX > RCH2X > CH3X
Page # 20
Example :
1.
2.
3.
4.
Page # 21
(B) Reaction with phosphorus trihalides
Several phosphorus halides are useful for converting alcohols to alkyl halides. PBr3, PCl3, & PCl5 work
well and are commercially available.
Phosphorus halides produce good yields of most primary and secondary alkyl halides, but none works
well with tertiary. alcohols. The two phosphorus halides used most often are PBr3 and the P4/I2 combi-
nation.
3R OH + PX3 3R X + H3PO3
Mechanism :
Step : 1
CH3 CH3
| PBr |
e.g. CH3 CH2 CH CH2 OH 3
CH3 CH2 CH CH2 Br
2 Methyl 1 bu tan ol 2 Methyl 1 bromobutane
e.g.
e.g.
Mechanism :
..
H .. .. O:
R O + HCl
.. S
Cl
Chlorosulphite ester
R Cl + SO2
In the first step, the nonbonding electrons of the hydroxy oxygen atom attack the electrophilic sulphur
atom of thionyl chloride. A chloride ion is expelled a proton and gives test of chloro sulphite ester.
Second step is an SN2 mechanism
Page # 22
SOCl 2
e.g.
Py
R Cl + SO2
H Cl
C
e.g. CH3(CH2)4CH2 CH3
(R)
2-Chlorooctane
84%
HX
+ X R + X R + X R
alkyl halide
HBr
e.g. (i) CH3CH2OCH2CH3 2CH3 CH2Br
excess
Mech.
Br
|
CH3 C H +
|
H
ethyl bromide
CH3CH2Br
Page # 23
Ex.3
CH3 CH3
HBr
2
Ex.4 CH3 C O CH2 CH3 CH3 C OH + CH3 CH2 Br (S N )
H H major
Me Me Me Me Me
HBr
Ex.5 Ph O H OH H + Ph Br + Br Ph
1
(SN )
Et D D Et Et
(Retention) (Racemisation)
2 3 2 4
HI
Ex.6 1 3 OH
1
1
O
4 (S N ) I
e.g.
(b) In acidic medium mechanism is SN1 type. Nucleophilic attacks on more substituted carbon.
Mechanism :
Nu
|
H
R CH CH2
|
OH
H O18
e.g. 2
H
e.g.
Page # 24
5. ELIMINATION REACTIONS
In an elimination reaction two atoms or groups (YZ) are removed from the substrate and generally
resulting into formation of bond.
| |
E lim ination
CC
YZ
| |
Y Z
-elimination : When two groups are lost from the same carbon atom to give a carbene (or nitrene).
This is also called 11 elimination.
CC:
XY
-elimination : When two groups are lost from adjacent atoms so that a bond is formed. This is also
called 12 elimination.
C=C
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
+ B H
# In the second step, a base abstracts a proton from the carbon atom adjacent to the carbocation, and
forms 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 # 25
Energetics
The free energy diagram for the E1 reaction is similar to that for the SN1 reaction.
Reactivity Order :
# Similar to SN1 becuase Carbocation Intermediate is formed in the rds step.
SN1 vs E1 :
In case of alkyl halide SN1 product is always more than E1 product
Example :
CH3
|
Ex.1 CH3 CH2 C CH3
|
Br
Ex.2 + and
CH OH,
3 + + +
Sol. CH OH
3
or
Page # 26
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, SN1 is major and E1 minor so, alkenes are not prepared by this method. water or
MeOH do not cause E1 (very weak base)
Y (d/) mixture of
and
Step 1 :
Step 2 : +
Step 3 +
Page # 27
Remarks
In first step, an acid-base reaction a proton is rapidly transferred from the acid to one of the unshared
electon 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 formation
of a hydronium ion and an alkene.
Reactivity of ROH : 3 > 2 > 1
Examples
CH2
CH2OH
Conc.H2SO 4
Ex.1 +
(I)
Minor
Ex.2
Ex.3
Ex.4
Ex.5 + +
Ex.6
Ex.7
Ex.8
Ex.9 H SO , Ex.10
2
4
Page # 28
Pinacol-Pinacolone rearrangement
Mechanism
Examples :
H SO / H SO /
Ex.1 2
4
Ex.2 2
4
Ex.3 + Ex.4
e.g. Conc.H 2 SO 4 /
Ethers dissolve in concentrated solutions of strong inorganic acids to from oxonium salts, i.e. ether behave
as bronsted Lowry bases.
+ -
R2O + H2SO4 (R O R) HSO4 R OH + R O SO 2 OH
| alkyl hydrogen
H sulphate
H
Ex.1 CH3 CH2 O CH2 CH3
2 3
H SO
Ex.2 2
4
1 4
O
Page # 29
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 an
alkene. Dehydrohalogenation can take place by E1 and E2 mechanism.
Reagents : -
(i) Hot alcoholic solution of KOH or EtO / EtOH (ii) NaNH2 (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 product
with 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 # 30
Examples :
e.g. +
CH3
|
e.g. CH3 C Br + + H2 O +
|
CH3
Formation of the Hoffmann product
Bulky bases can also accomplish dehydrohalogenations that do not follow the saytzeff rule. Due to
steric hindrance, a bulky base abstracts a less hindered proton, often the one that leads to formation
of the least substituted product, called the Hoffmann product.
H CH3
| |
CH3 C C CH2 +
| | |
H Br H
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)
6. Stereospecific reaction means the one stereoisomer gives one stereoisomer as a product
CH3 Ph
H CH3
Br H Br
CH3
Ph H
Ph Ph
Trans
CH3 Ph
H
Examples : Page # 31
Ex.1
Ex.2
Ex.3 Alc.KOH
No. reaction
Ex.4 +
Ex.7 Alc.KOH
Ex.8
H
Ex.9
Page # 32
Ex.10
Promoting factors E1 E2
(i) Base W eak base Strong base required
Characteristics
(i) Kinetics K [R X] Ist order K [R X] [Base] IIst order
(ii) Orientation Saytzeff alkene Saytzeff alkene
No special geometry transition state
(iii) Stereochemistry
is required must be co-planar
X: H
E1:
1 rds
RCH=CH
2
2
E2:
1 RCH=CH2
Ex.1
Ex.2
Page # 33
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
H
| |
CC X (Conjugate base)
| |
Step - II : Carbanion looses a leaving group to form alkene
C C
| |
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 time
interval, 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
Ex.1
Page # 34
Ex.2
Ex. 3 R2C=O
Ex.4
Note :
1. CH I excess
Ex.6 3
2. AgOH /
1. CH I excess
Ex.7 3
2. AgOH /
Ex. 8
Ex.9
Page # 35
Faculty Remark
Your suggessions / deficiencies are invite regarding this lecture note in detail.
please submit to the R & D coordinator (Organic chemistry)
S.No.
1.
2.
3.
4.
5.
Page # 36