Nucleophilic aliphatic substitution

1. Homolytic and heterolytic chemistry

Chemical change: The conversion of one molecule

into another.

Old bond must be broken

New bond must be formed

The breaking of a covalent bond can take place in

two fundamentally different ways, depending upon

what happens to the two electrons making up the

bonding pair.

Nucleophilic aliphatic substitution

In homolysis, one electron goes to each fragment.

In heterolysis, both electrons go to the same

fragment.

Homolytic reactions: Those reactions in which the electrons

of the bonding pair are taken away or provided singly.

Whether bonds are being broken or formed or simultaneously

broken and formed, each of the atoms being separated takes

one of the bonding electrons and each of atoms being joined

together provides one of the bonding electrons.

A : B A B (Bond broken)

A B A : B (Bond formed)

A : BC C:A (Simultaneously bond broken and formed)B

Nucleophilic aliphatic substitution

Heterolytic reactions: Those reactions in which

the bonding electrons are taken away or

provided in pairs. Whether bonds are being broken or

formed or simultaneously broken and formed, each of the

atoms being separated takes both bonding electrons and one

of the atoms being joined together provides both electrons.

Homolytic chemistry: The chemistry of odd electron.

Heterolytic Chemistry: The chemistry of the electron pairs.

Homolytic chemistry deals the neutral particles called free

radicals.

Heterolytic chemistry deals with positive and negative

charges, with cations and anions.

Nucleophilic aliphatic substitutionA : B A :B (Bond broken)

A :B A : B (Bond formed)

A : BC: C:A :B (Simultaneously bond broken and formed)

Nucleophilic aliphatic substitution

Homolyric reactions are are typically

carried out in the gas phase or in solvents

whose principal function is to provide an

inert medium in which the reacting

molecules can move about.

Heterolytic reactions are typically

carried out in solutions and the solvents

exerts powerful effects.

The large part of the chemistry is

heterolytic and it is the kind that will take

up most of our time.

Nucleophilic aliphatic substitution

2. Relative rates of competing

reactions :

In a reaction vessel there is a collection

of molecules colliding with one another.

In principle, a number of reactions can

conceivably undergo. Which of these

reactions actually takes place is the one

that goes fastest. Chemical behavior

thus come down to a matter of relative

rates of competing reactions.

Chemical behaviors depends on the

molecular structure.

Nucleophilic aliphatic substitution

In our study of nucleophilic

substitution, we shall have much to do

with competition between reaction

pathways; competition between

different mechanisms for

substitution itself (SN1 and SN2) and

competition between substitution

and elimination (Elimination won’t

be discussed).

Nucleophilic aliphatic substitutionReactions of alkyl halides : Nucleophilic aliphatic substitution :

CH3:Br :OH CH:OH :Br

Methyl bromide

Hdroxide ion

Methanol Bromide ion

It is one of the example of heterolytic

nucleophilic alipahtic substitution.

Nucleophilic substitution is characteristic

of alkyl halides.

Nucleophilic aliphatic substitution

Nucleophilic substitution is

characteristic of alkyl halides -

explain why this is so.

A halide ion is an extremely weak base

( their hydrogen halides are strong acids).

In an alkyl halide, halogen is attached to

carbon; and, just as halide readily

releases a proton, so it readily releases

carbon – again, to other bases. These

bases poses an unshared pair of electrons

and are seeking a relatively positive site,

that is, are seeking a nucleus with which

to share their electron pairs.

Nucleophilic aliphatic substitution

Nucleophile :

Electron-rich reagents that tend to attack the

nucleus of carbon are called nucleophilic reagents

or simply nucleophiles.

Nucleophilic substitution :

When the attack results in substitution, the

reaction is called nucleophilic substitution.

Substrate :

The carbon compound on which substitution takes

place is called the substrate.

Leaving group :

The group that becomes displaced from carbon

and taking the electron pair with it, is called the

leaving group.

Nucleophilic aliphatic substitution

In general,

Note :

1)The nucleophile, :Z can be negatively

charged or neutral [for example, OH¯, CN¯,

(negatively charged) H2O, NH3 (neutral)

etc]. An unshared pair of electrons is

their characteristic feature.

2)The product R:W will then be neutral or

positively charged.

3)The leaving group, :W¯ will then be

negatively charged or neutral.

R W R WZ Z

Substrate Nucleophile Product Leaving group

Nucleophilic aliphatic substitution

Nucleophilic aliphatic is one of the four

most useful classes of organic reactions.

1.Nucleophilic addition (characteristic of

aldehydes and ketone)

2.Nucleophilic alipatic substitution

(characteristic of alkyl halides) and

nucleophilic acyl substitution

(functional derivatives of carboxylic acids).

3.Electrophilic addition ( Alkenes and

alkynes)

4.Electrophilic aromatic substitution

(arenes and their derivatives)

Nucleophilic aliphatic substitution3. Reactions of alkyl halidesA large number of nucleophilic substitutions are listed below to give an idea of the versatility of alkyl halides. R X R XZ Z

R X OH R OH X

H2O R OH

OR' R OR'

C CR' R C CR'

R'-M R R'

I R I

Alcohol

Ether

Alkyne

Alkane

Alkyl iodide

Nucleophilic aliphatic substitutionR X R XZ

R CN

R'COO

R

R NHR'

R NR'R"

CH2NH2

R'COO R

NH3 NH2

NH2R'

NR'R"

P(C6H5)3 R P(C6H5)3

SH R SH

SR' R SR'

Z

Nitrile

Ester

1˚ amine

2˚ amine

3˚ amine

Phosphonium salt

Thiol (mercaptan(

(Thioether (sulphide)

Nucleophilic aliphatic substitution

4. Nucleophiles and leaving group

The components required for nucleophilic

substitutions are :

1)Substrate ( substrate consists of two

parts : (i) alkyl group and (ii)leaving

group.

2)Nucleophiles

3)Solvents

R W R WZ Z

Substrate Nucleophile Product Leaving group

Alkyl group Leaving group

Solvent

Nucleophilic aliphatic substitution

We came to know that the reactivity of

nucleophile aliphatic substitution affected

by mainly four factors :

1)The effect of alkyl groups

2)The effect of leaving groups

3)The effect of nucleophiles

4)The effect of solvents

Nucleophilic aliphatic substitution

Nucleophiles and leaving groups :

Basicity plays an important role in

understanding of nucleophiles and

leaving groups.

Nucleophiles are characterized by being

bases and leaving groups are being

characterized by being weak bases.

The stronger of two bases is often the

more powerful nucleophiles and the

weaker of two bases is often the better

leaving group.

Fundamental differences between

basicity and nucleophilic power or

leaving ability:

1)Basicity is a matter of equilibrium;

nucleophilic power and leaving ability are

matters of rate.

Of two bases, one is said to be the stronger

because at equilibrium it holds a greater

proportion of the acid.

Of two nucleophiles, one is said to be the

more powerful because it attacks carbon faster.

Of two leaving groups, one is said to be the

better because it leaves carbon faster.

Nucleophilic aliphatic substitution

Nucleophilic aliphatic substitution

2) Basicity (in the Lowry-Bronsted

sense) involves interaction with

proton; nucleophilic power and

leaving ability involve interactions

with carbon.So far we have used alkyl halides as our chief

examples of substrate .But these reactions take

place in exactly the same way with a variety of

other substrate: compounds which, like alkyl

alkyl halides, contain good leaving group. Of

these other substrate, alkyl esters of

sulphonic acids, ArSO2OR, are most

commonly used in place of alkyl halides.

Sulphonates are good leaving group. ArSO2O-R

+ :Z → R-Z + ArSO3¯

Nucleophilic aliphatic substitution

H3C S Br S

O

O O

O

S

O

O

H3C S

O

O

F3C

Tosyl or Ts Brosyl or Bs

M esyl or M s Trif yl or Tf

Most commonly used are esters of p-toluenesulphonic acid : the p-toluenesulphonates.

Nucleophilic aliphatic substitution

5. Rate of reaction : effect of

concentration – kinetics

The rate of a chemical reaction can be

expressed as a product of three factors :

rate = collision frequency x energy factor

x probability factor

The field of chemistry that deals with

rates of reaction, and in particular with

dependence of rates on

concentration, is called kinetics.

Nucleophilic aliphatic substitution

6. Kinetics of nucleophilic aliphatic

substitution : Second – order and

first – order reactions

Let us take a specific example;

CH3Br + OH¯→ CH3OH + Br¯

If the reaction results from collision between a

hydroxide ion and a methyl bromide molecule,

we would expect the rate to depend upon the

concentration of both these reactants. If either

OH¯ concentration, [OH¯], or CH3Br

concentration, [CH3Br], is doubled, the collision

frequency should be duobled and the reaction

rate doubled. If either concentration is cut in

half, the collision frequency, and consequently

the rate, should be halved.

Nucleophilic aliphatic substitution

Therefore, the rate of reaction depends

upon both [OH¯] and [CH3Br] and we

indicate this by the expression

rate = k[CH3Br][OH¯] ( k is rate constant)

At a given temperature and for a given

solvent, k always has the same value and

is characteristic of this reaction,

Now let us look at the corresponding

reaction between tert-butyl bromide and

hydroxide ion:

H3C C Br

CH3

CH3

OH H3C C OH

CH3

CH3

Br

Nucleophilic aliphatic substitution

As before, if we double [RBr], the rate

doubles; if we cut [RBr] in half, the rate is

halved. Bt if we double [OH¯], or if we cut

[OH¯] in half, there is no change in the

rate. The rate of reaction is independent

of [OH¯].

Therefore, the rate of reaction is

indicated by this by the expression

rate = k[CH3Br]

The first reaction is reffered toas second

– order kinetics and the second

reaction is said to be first – order

kinetics.