http://www.public.asu.

edu/~iangould/ CHM 331/332 handout (page 1 of 3)

NUCLEOPHILICITY, BASICITY AND LEAVING GROUP ABILITY
____________________________________________________________
Nucleophilicity
Nucleophilicity Nucleophile Conjugate Acid Approx. pKa
I

HI -10
Very Good HS

H
2
S 7
RS

RSH 8
Br

HBr -9
Good HO

H
2
O 15
RO

ROH 18
CN

HCN 9
NH
3
NH
4
+
9
Fair Cl

HCl -7
F

HF 3
RCO
2

RCO
2
H 5
Poor H
2
O H
3
O
+
-2
ROH RO
+
H
2
-2
Very Poor RCO
2
H RCO
+
HOH -7
Note the poor relationship between nucleophilicity and basicity. Many other
factors control nucleophilicity such as physical size and polarizability.
The following trends can be noted:
1. Species with negative charges are stronger nucleophiles than
corresponding uncharged species

OH > H
2
O

SH > H
2
S

NH
2
> NH
3
2. Nucleophilicity decreases going to the right in the periodic table. More
electronegative elements tend to "hold" their electrons more tightly

OH >

F NH
3
> H
2
O R
3
P > R
3
S
3. Nucleophilicity increases going down the periodic table as polarizability
increases.

I >

Br

Cl >

SeH >

SH >

OH R
3
P > R
3
N
http://www.public.asu.edu/~iangould/ CHM 331/332 handout (page 2 of 3)
Basicity
Base Conjugate Acid Approx. pKa
RCC

(alkyne) RCCH 20
RO

ROH 18
HO

H
2
O 15
NH
3
NH
4
+
9
NC

HCN 9
RS

RSH 8
RCO
2

RCO
2
H 5
ArNH
2
ArNH
3
+
4
F

HF 3
ArSO
3

ArSO
3
H -7
Cl

HCl -7
I

HI -10
When a reagent reacts with an alkyl halide in an S
N
2 reaction, it is acting as a
nucleophile; when it reacts in an E2 reaction, it acts as a base. Here are data
which allow base strengths to be compared. Strong bases have weak conjugate
acids (their pKa's are large and positive), and weak bases have strong conjugate
acids (their pKa's are negative).
Although it is not possible to predict the rate at which a reagent will undergo an
S
N
2 reaction from this data (see the table on the previous page), it is clear that
the rate of any E2 reaction which might occur in competition with S
N
2 will be
determined by base strength. Thus, the reagents towards the bottom of the table
are less likely to undergo E2 in competition with S
N
2 simply because they are not
strong enough bases. The reagents towards the top of the Table are more likely
to undergo E2 in competition with S
N
2.
So, when a reagent from the top of the table is added to an alkyl halide, which
reaction will occur, S
N
2 or E2? This may be determined by the alkyl halide itself.
Remember, S
N
2 is fastest for 1
Y
halides so this is the most likely reaction in this
case. S
N
2 doesn't happen at all for 3
Y
halides, so E2 must occur. E2 also tends
to be fastest for 3
Y
and slowest for 1
Y
halides because of the stabilities of the
alkenes which are formed.
http://www.public.asu.edu/~iangould/ CHM 331/332 handout (page 3 of 3)
Leaving Group Ability
Leaving Group Approx. Relative Rate Conjugate Acid Approx. pKa
HO

very small H
2
O 15
F

0.00001 HF 3.5
Cl

1 HCl -7
Br

10 HBr -9
H
2
O 10 H
3
O
+
-1.7
I

100 HI -10
TsO

100,000 TsOH -2.8

CF
3
SO
2
O

100,000,000 CF
3
SO
3
H -6
Note that here there is a rough relationship between leaving group ability and
basicity. Very basic groups are poor leaving groups. Consider the reactions of
alcohols. Substitution does not take place for alcohols (HO

is too poor a leaving

group, the pKa of the conjugate acid, H
2
O, is approx. 15) unless the alcohol is
protonated, then the leaving group becomes H
2
O (pKa of the conjugate acid,
H
3
O
+
, is approx. -2).
A good leaving group should have the following properties:
1. It should polarize the bond which connects it to the carbon so that the
carbon has some positive charge, making it more reactive towards the
nucleophile; i.e., it should be electron withdrawing.
2. It should want to leave with a pair of electrons; i.e., it should be a stable
"anion" (not all leaving groups are anionic), which means it is unlikely to be a
strong base.
3. It should be polarizable to distribute charge in the transition state.