NUCLEOPHILIC SUBSTITUTION

THE GENERAL REACTION AND TERMINOLOGY

SUBSTITUTION REACTIONS
One group takes the place of another.

Y +

Y +

Y Y

takes the place of displaces

( Substitution )

NUCLEOPHILIC SUBSTITUTION
NUCLEOPHILIC DISPLACEMENT substrate leaving group

Nu: - +
nucleophile

R Nu +
product

:X-

The nucleophile displaces the leaving group.

This is a substitution reaction : Nu substitutes for X (takes its place).

IMPORTANT:
This is a reaction at sp3 (tetrahedral) carbon atoms.
sp3 sp2 sp
C C X X C C X

yes

no

Compounds that have sp2 or sp carbons generally do not give nucleophilic substitution reactions.
.. of course there are a few special cases that do react, but we wont discuss them in this chapter.

EXAMPLES

EXAMPLE 1

NaI + CH3 Br

acetone

CH3 I

+ NaBr (s)

soluble

insoluble

iodide displaces bromide at carbon

* NaI is soluble in acetone, NaCl and NaBr are not

EXAMPLE 2

CH3 H3C C Cl + 2 H2O CH3

CH3 H3C C OH + H3O + + ClCH3

COMPARE THESE SUBSTITUTIONS

DISPLACEMENT AT CARBON

Nu: - +
nucleophile

R Nu +
product

:Xleaving group

substrate

DISPLACEMENT AT HYDROGEN

B:

:X

base

acid

conjugate conjugate acid base

THESE REACTIONS HAVE A WIDE RANGE OF SUBSTRATES

COMMON SUBSTRATES
( Leaving group varies )
alcohols
+ R OH R O H H
alcohols require acid and then H2O leaves see Table 10-3

alkyl halides

R Cl R Br R I

tosylates
O R O S O CH3

ABBREVIATION

R O

Ts

alkyl p-toluenesulfonate

THERE IS ALSO A WIDE RANGE OF NUCLEOPHILES

A WIDE VARIETY OF COMPOUNDS CAN BE MADE

NUCLEOPHILES
R-Y + Nu R-Nu + Y

see Table 10-4

A WIDE SELECTION OF NUCLEOPHILES MAKES POSSIBLE THE SYNTHESIS OF MANY TYPES OF ORGANIC COMPOUNDS:

Nucleophile
Cl ,Br ,I
OH
-

Product
R X

Class
alkyl halides

- -

R OH R O R R C N O
R' C O R

alcohols ethers
nitriles

RO

C N -

O R' C O-

esters
alkynes thiols

R' C C:SH
-

R' C C R R SH

THE NUCLEOPHILE DOES NOT HAVE TO BE CHARGED

H O H + R Br H O R + Br H O H H H O R + H3O + + B r
-

Under some circumstances water will react.

Nucleophile
H O H R O H

Product
R O H
R R O

Class alcohols ethers amines amines

NH3
R' NH2

R NH2
R' NH R

LOOK-ALIKE REACTIONS
RBr + NaOH ROH + NaBr

Two reactions follow.... Both appear to be identical and follow the general pattern shown above. However, they are different !

TWO LOOK-ALIKE REACTIONS

RBr + NaOH ROH + NaBr
80% ethanol 20% water 55oC

1)

CH3 Br + NaOH

CH3 OH + Br

rate = k2 [RBr] [NaOH] 2)

high conc. NaOH

CH3 H3C C Br + NaOH CH3

rate = k1 [RBr]
80% ethanol 20% water 55oC

CH3
Br H3C C OH +

( + some alkene by E1,E2 )

CH3

low conc. NaOH

Notice that substrate in reaction 1 has no b-hydrogens .. why not?

REACTION 1 THE SN2 REACTION

CH3 Br + NaOH

80% ethanol 20% water 55oC

CH3 OH + Br

rate = k2 [RBr] [NaOH]

k2 = 0.022 liter/mole-sec

H O

CH 3 Br
80% ethanol 20% water

CH3 OH + Br

bimolecular concerted

SN2

substitution nucleophilic bimolecular

Concerted (one step) reaction

transition state TS

E N E R G Y

SN2

Ea

starting material

DH product

REACTION 2 THE SN1 REACTION

CH3 H3C C Br + NaOH CH3

80% ethanol 20% water 55oC

CH3
H3C C OH + Br

rate = k1 [RBr]

CH3
k1 = 0.010 liter/mole-sec

CH3 H3C C Br + NaOH CH3

80% ethanol 20% water

CH3 H3C C OH + Br CH3

-

unimolecular two steps

slow
O H CH3 H 3C C + CH3 + Br
-

fast
also

SN1
substitution nucleophilic unimolecular

alkene (via E1)

TWO STEP REACTION

TS1 carbocation intermediate TS2 Ea2 Ea1

SN1

E N E R G Y

starting material

step 1

step 2

DH product

TWO STEP REACTION

carbocation intermediate TS2

E N E R G Y starting material

TS1

SN1

Ea1

Ea2 DH

step 1

step 2

product