c


c
c
 c

These comments summarize the two substitution mechanisms and the two elimination
mechanisms encountered for alkyl halides.

  
!.


Kinetics Rate = k [RX] [Nu ]. Both RX and Nu are involved in the rate
determining step.

Nucleophile 
"#$ 
 %&! ' #!(#)*!+,ÿ occasionally
neutral nucleophiles can be used. See examples at the end of Handout.

þeactivity of alkyl halides c -.-. due to steric effects that hinder backside
attack. . halides do not react. Allyl (CH2=CH CH2X) and benzyl (C6H5CH2X)
halides are unusually reactive (comparable to or more reactive than methyl).

itereochemistry c!(#"!!/ !/ '

! via pentacoordinate carbon
Transition State.

þearrangements!!! '

iolvents Wide variety can be used, but polar, aprotic solvents (see end of Handout)
are favored and usually cause 2° halides to react by this mechanism.

Transition itate

Examples The S 2 reaction is concerted, with all bonds being made and broken at the
N

same time.
  
!.


Kinetics Rate = k [RX]. Only RX is involved in the rate determining step.

Nucleophile '
#&*
+' #!(#)*!+,ÿ see examples at the end of
Handout.

þeactivity of alkyl halides 3° > 2° %'!#

"
,#!/
,!
!

/!&# ! // ). Methyl and 1° halides do not
react. Allyl and benzyl halides are unusually reactive due to the exceptional stabilities
of the allyl and benzyl carbocations (resonance effects).

itereochemistry 

#
0
! via intimate and solvent separated ion pairs.

þearrangements  '/
!
,#
,!
!
/!.

iolvents Wide variety can be used, but polar, protic solvents (see end of Handout) are
favored and usually cause 2° halides to react by this mechanism.

Transition itate
Examples The S 1 reaction occurs in several steps, with formation of the carbocation
N

being involved in the first, rate determining step (see Transition State section above).

c
,!
! are involved in this mechanism, with some features of carbocations
being
itability 3° > 2°. The more stable an intermediate is, the more easily it is
formedÿ hence the relative reactivities of and halides. Methyl and 1°
carbocations are seldom formed. Allyl and benzylcarbocations form readily
because of resonance stabilization of the positive charge.
þearrangements If possible, a carbocation may rearrange!
!
,#
! by an alkyl group shift or a hydride shift. The most common rearrangement
is from a 2° to 3° ion. Primary carbocations, if formed (and they seldom are),
could rearrange to either a 2° or 3° cation.

Example

c!(
!!/ 
%  
!
 
rom a practical standpoint, S 2 reactions are useful for introducing various functional
N

groups in place of halogen in 1° and 2° halides. Only one substitution product is

formed, and many different nucleophiles can be used. Optically active halides cleanly
invert their stereochemistry in a S 2 reaction.
N

S 1 reactions are considerably less useful for several reasons. Only a limited number
N

of nucleophiles may be used, possible carbocation rearrangement can lead to multiple

products and racemization of the optically active substrates.

c
 
!

Kinetics Rate = k [RX] [B ]. Both RX and B are involved in the slow, rate
determining step.

The base Strong bases, such as KOH/alcohol or NaOCH2CH3 (NaOEt), are required.

þeactivity of alkyl halides .-.-.. With a strong base, alkyl halides undergo
elimination by the E2 reaction.

þearrangements Do not occur

iolvents Reaction can occur in a variety of solvents. The use of a strong base is the
driving force for elimination to occur.

þeactants
1) Must have one or more hydrogens.
2) H and the leaving group must be anti to one another and must be in the same
plane as the two carbons to which they are attached.

Products If two or more alkenes are produced, the one having the greater or greatest
number of carbon containing substituents attached to the C=C bond is usually
the 
1! product. The reason for this trend is based upon the stabilities of various
alkenes, with the more or most stable alkene being formed more easily and thus is the
major product.

2sotope Effects Because breaking the C H bond is involved in the rate determining
step, the use of D in place of H results in different rates of reaction because it is more
difficult to break a C D bond than a C H bond. or example, CD3CH2Br undergoes
E2 elimination more slowly than CH3CH2Br.

Transition itate
Examples The E2 reaction is a ! %
!, with all bonds being made and
broken at the same time.


 
!

Kinetics Rate = k [RX]. # 2 is involved in the slow, rate determining step.

The base ‰
+#,
 ',
 , such as H2O, CH3OH, and CH3CH2OH can
cause elimination to occur by the E1 reaction.

Reactivity of alkyl halides .-.-. halides usually do not undergo E1

reaction.! If a strong base is present, E2 reaction occurs.

þearrangements If possible, a carbocation may rearrange !

!
,#! by
an alkyl group shift or a hydride shift. The most common rearrangement is from a 2°
to 3° ion. Primary carbocations, if formed (and they seldom are), could rearrange to
either a 2° or 3° cation.

Rearrangement occurs !

(%# than does the loss of a proton from a
carbocation, so rearrangement products ''
##(%!
.
iolvents Reaction is favored in (!#
(! !#".

þeactants:
1) Must have one or more hydrogens.
2) Unlike the E2 reaction, no special geometry is required.

Products If two or more alkenes are produced, the one having the greater or greatest
number of carbon containing substituents attached to the C=C bond is usually
the 
1!(!%' . The reason for this trend is based upon the stabilities of various
alkenes, with the more or most stable alkene being formed more easily and thus is the
major product.

2sotope Effects !. The rate determining step doesn't involve breaking a C H or a

C D bond. or example, (CH3)3CBr undergoes E1 elimination at the same rate as
(CD3)3CBr.

Transition itate

Examples The E1 reaction ! '"

#(, with formation of the carbocation
being involved in the first, rate determining step (see Transition State section above).
 c!(
!!/

%
 
!

rom a practical standpoint, E2 reactions are useful for converting alkyl halides into
alkenes, even when a mixture of alkenes is formed. E2 reactions can be carried out on
any class of alkyl halide.

E1 reactions are considerably less useful for converting alkyl halides into alkenes. In
addition to formation of the mixture of alkenes, more elimination products yet can be
formed if a carbocation rearrangement is possible.

c!(!* 
%
 
!


Unlike the S 2 and E2 reactions that occur by different mechanisms, the S 1 and E1
N N

reactions have one thing in common both involve the initial formation of
a
,!
!%
 resulting from the solvent assisted ionization of the C X
bond. Once formed, the carbocation may undergo several type of reactions

1. react with a nucleophile to give products

2. lose a proton from the carbon(s) to give one or more alkenes
3. rearrange to a more stable carbocation that undergoes reactions 1) and 2)

E1 and S 1 reactions occur with 2° and 3° halides but not with 1° halides. They occur
N

with neutral, weakly basic nucleophiles such as H2O and ROH. Both mechanisms
compete to give substitution and elimination. With any 2° halide, always consider
possible carbocation rearrangements.
In the examples that follow, pay particular attention to the class of alkyl halide and the
solvent if specified. These features indicate if both substitution and elimination occur.
You should be able to identify the type of mechanism (E1 or S 1) and identify the
N

major alkene formed in elimination.<

c!(!*

%
 
!.

S 2 and E2 reactions compete to give substitution and elimination. This competition

N

exists when alkyl halide is 1° or 2°ÿ with 3° halides, elimination is the only reaction of
importance. Primary halides generally undergo substitution much more readily than
elimination,'#,
"! 
%,'#+

Nucleophiles that are basic, such as OH , result in competition. A limited number of

nucleophiles, such as , are*
+#,
 (soft bases) and hence cause only substitution
to occur without any elimination.

In the examples that follow, pay particular attention to #

!/
#+#
#%
%

'!/' #!(#&*
+!! ,
), and the solvent if specified.
These features dictate the type of mechanism(s) and whether substitution and/or
elimination occurs. You should write mechanisms for each example. You should be
able to identify the type of mechanism (E2 or S 2) and identify the major alkene
N

formed in elimination.
Ë !*!
#0!,#

To properly determine the correct or most plausible mechanism(s) for substitution

and/or elimination, consider the following factors. This is precisely the analysis that
was done in the examples given above.

c#
/
#%&...)
%%/' #!(#. Is the latter negatively
charged or neutral? Is it a soft or a hard base?


3

 

#
%/ "(!%' 
a) If the nucleophile is on a different carbon than the leaving group or if the
carbon skeleton has changed, consider SN1 and carbocations for substitution,
and E1 for elimination.
b) If the nucleophile is on the same carbon as the leaving group and there is no
change in the structure of the carbon skeleton, consider SN2 and for
substitution, and E2 for elimination.
 
% ' #!(#4,

a) If it is negatively charged and a 
%,
, consider iN2 and for
substitution, and E2 for elimination.
b) If it is negatively charged and a !/,
, consider iN2 (there will be no
substitution if halide is 3° and no elimination unless the solvent is polar,
protic). If it is '
#, consider iN1 and E1.
ù%/ #
!/
#+#
#%
a) If primary, consider iN2 and/or E2.
b) If secondary, consider iN2 or E2 (in aprotic solvent) or iN1 or E1 (in polar,
protic solvent).
 c) If tertiary, consider iN1 or E1 only.

r.
#%

,! !,
!!/
!
. The
mechanism is often dictated by the solvent. Aprotic polar solvents favor SN2/E2 and
polar, protic SN1/E1.

5/
.
,!
!/!%
#*
 !%(!,#

 !

!
,#.
,!
!&c
,!
! !
,!").

c
 


‰
+ 
 % nucleophiles (soft bases) (avor SN2).

OH , CN , I , RS

2. ‰
+'
# nucleophiles (soft bases) (avor SN1 and E1)

ROH, H2O, RSH, R3P

3. ! ' #!(# (hard bases) (avor SN2 and E2)

Cl , RNH2, RCO2 (mainly SN2)

 , RO , HO /alcohol, NH3, CO32 (mainly E2)

6


1.!#
(! solvents (good H-bonding donors and acceptors) (avor SN1 and
E1).

ROH, H2O, RNH2, liq. NH3, CH3CO2H

2. !#

(! solvents (no H-bonding, but good dipoles) (avor SN2 and E2).

A. Wingrove

L. Ryzhkov
August, 1996