CHEM 331

Problem Set #3: Substituent Effects and LFERs

Submit answers to even numbered questions only. Due Monday, Mar. 21st

1. The structure of the herbicide sulcotrion has is shown below and is found to have a pKa of 3.13. Draw the
structure of the conjugate base and explain the unusual acidity of this ‘carbon acid’.

O O Cl

O
O S
O
sulcotrion

Solution:

The hydrogen atom α- to the three carbonyl groups is the most acidic due to the extensive resonance stabilization of the
negative charge in the conjugate base (enolate ion).

O O Cl O O Cl
H
-
(-H+)

O SO2CH3 O SO2CH3

-
O O Cl O O Cl O O Cl
-

O SO2CH3 O SO2CH3 O SO2CH3

-

There are also additional inductive and resonance stabilizing effects resulting from the ortho chlorine and para sulfone, σp =
0.72.

PS 3 2016 Solutions
2. Answer each of the following with reference to the corresponding substituent constants considering both
inductive and resonance electronic contributions (σI and σR). Illustrate your answer showing resonance structures
for substituted benzoic acids, where appropriate.

a) The σmeta and σpara values for the –CO2CH3 group are both positive with σpara > σmeta.

b) The values of σmeta for the methoxy substituent (–OCH3) is positive, whereas the values for σpara is
negative.

c) The picryl (2,4,6-trinitrophenyl) substituent, -C6H2(NO2)3 is relatively large with the ortho nitro groups
sterically interfering with atoms in the ortho positions on an adjacent aromatic ring. Predict the sign and
relative magnitude of σmeta and σpara for the picryl substituent.

Solution:
In the meta position, electronic effects are governed largely by inductive effects (differences in electronegativities), i.e., σmeta ~
σI. In the para position however both inductive and resonance contributions manifest and hence σpara ~ σI + σR.

a) The σmeta and σpara values for the –CO2CH3 group are 0.33 and 0.45, respectively. This carbomethoxy group is therefore
electron withdrawing by both inductive and resonance effects. The carbonyl carbon (C=O) is bears a slightly positive charge as
a result of the more electronegative oxygen atoms it is bonded to, giving rise to an inductive withdrawing effect. We can
roughly say that σI ~ 0.33 and σR ~ 0.12.

Moreover, the carbonyl carbon is sp2 hybridized and can therefore participate in resonance when bonded to an aromatic ring.
The extra resonance structure in which the negative charge resides on the carbonyl oxygen contributes to the withdrawing
ability of this substituent as depicted below.

b) The σmeta and σpara values for the –OCH3 group are 0.12 and -0.27, respectively. This means that the methoxy group is
electron withdrawing by induction and electron donating by resonance. In the meta position, the electronic effect is governed
by the fact that the oxygen of the methoxy group bonded to an aromatic carbon is more electronegative and σI ~ 0.12.
However, in the para position we have additional resonance effects as a result of the lone pair electrons on oxygen being
donated back into the aromatic ring (depicted below). The observed σpara value is the sum of both effects and is net donating.
We can therefore estimate that σR ~ -0.39.

c) The picryl substituent is electron withdrawing due to the inductive effect of the three nitro groups pulling electron density
from the aromatic ring. There is no appreciable resonance contribution when picryl is in the para position as can be seen by
the fact that σmeta ~ σpara (0.42). This lack of resonance contribution can be understood by considering the large steric
interactions that result in a significant twist angle between the two aromatic rings. The extent of conjugation drops off steeply
with the dihedral angle between adjacent p-orbitals. Hence σR ~ 0 in this case.

PS 3 2016 Solutions
3. Using the information in Table 1 and 2 (attached), estimate the pKa values of the following compounds at 25°C
and sketch a plot of the fractional abundance of each acid and conjugate base over a pH range of 0 – 14.

a) 3,4-dinitrophenol

b) 2,4-dichlorophenoxy acetic acid

c) the conjugate acid of para-methylaniline

Solution:

Rearranging the Hammett equation, we can estimate the pKa of acidic compounds provided we know the pKa of the parent
system under the same conditions (solvent, temperature etc) and the appropriate substituent constants.

⎛ K (X) ⎞
log⎜⎜ a ⎟ = ρ Σσ
⎟
⎝ K a (H) ⎠
∴ pKa(X) = pKa(H) – ρ Σ σx

a) 3,4-dinitrophenol

pKa(phenol) = 9.92, ρ = 2.25

pKa(3,4-DNP) = 9.92 – 2.25 ((1.25) + (0.71)) = 5.49

(note the use of σ for the 4-NO2 substituent)

−

b) 2,4-dichlorophenoxy acetic acid

pKa (2-chlorophenoxy acetic acid) = 3.05, ρ = 0.30

pKa(2,4-DCP) = 3.05 – 0.30 (0.23)) = 2.98

c) the conjugate acid of para-methylaniline

pKa (aniline) = 4.63, ρ = 2.89

pKa(4-MA) = 4.63 – 2.89 (-0.17) = 5.12

PS 3 2016 Solutions
4. The pKa values of m- and p-monosubstituted benzoic acids in 50% aqueous ethanol correlate with σ, and have a
ρ value of 1.60. The pKa of benzoic acid in this system is 5.71. The pKa values of some 4-X-3,5-dimethylbenzoic
acids in this solvent system are given below. Use these results to examine and comment on the applicability of
additivity of σ values.

X N(CH3)2 NH2 Cl Br CN COOCH3 NO2

pKa 6.23 6.88 5.59 5.55 4.90 5.44 4.91

Solution:

We can calculate the pKa for each of the trisubstituted benzoic acids using the Hammett equation and a ρ value of 1.60, a
pKa(H) = 5.71 and the sum of the three substituent constants. In so doing, we are making the assumption that each substituent
will have the same electronic effects in 3,4,5-trisubstituted benzoic acids as they would if they were present by themselves. In
general, this will be true provided that there are not overriding factors that influence their degree of contribution. Since in the
present case, we are looking at the effect of placing a group in the 4-position between two other substituents, we should
consider the possibility of steric hinderence on resonance contributions.
⎛ K (X) ⎞
log⎜ ⎟ = ρ Σσ
⎜K ⎟
⎝ (H) ⎠
∴ pKa = 5.71 – 1.60(σx -0.14)

X N(CH3)2 NH2 Cl Br CN CO2CH3 NO2

Expt’l pKa 6.23 6.88 5.59 5.55 4.90 5.44 4.91
Calc pKa 7.26 6.99 5.57 5.57 4.88 5.21 4.69
Difference 1.03 0.11 0.02 0.02 0.02 0.23 0.22

Although there is good agreement between the experimental pKa’s and those calculated based on adding the substituent effects,
there are some significant differences. In general, the agreement is best for relatively small substituents with relatively small
resonance components (σR) such as Cl and Br. The larger groups, such as N(CH3)2, CO2CH3 and NO2 show the greatest
deviation. If we assume that N(CH3)2 has no resonance contribution and use the σI ~ σm, we calculate a pKa of 6.01, which
improves the agreement. Larger groups in the 4-position will experience greater steric interactions with the methyl groups and
will be twisted out of the plane of the aromatic ring. This dramatically reduces the orbital overlap between 2p orbitals on the
substituent with the pi-system of the aromatic and consequently reduces σR.

CO2- CO2-

H3C CH3 H3C CH3

N +
N
H3C CH3 H3C CH3
Note that the agreement is better for NH2 than N(CH3)2 since it is smaller in size and the out of plane twist is not as dramatic
such that much of it’s resonance contribution is retained.

PS 3 2016 Solutions
Another approach to this question involves graphing the experimental pKa values against the sum of sigma substituent
constants to analyze the fit.
log
σ exp. pKa(X) Ka(X)/Ka(H)
4-X 3,5-diMe Σσ
N(CH3)2 -0.83 -0.14 -0.97 6.23 -0.9500
NH2 -0.66 -0.14 -0.80 6.88 -0.3000
Cl 0.23 -0.14 0.09 5.59 0.3400
Br 0.23 -0.14 0.09 5.55 0.3800
CN 0.66 -0.14 0.52 4.90 1.0300
CO2CH3 0.45 -0.14 0.31 5.44 0.4900
NO2 0.78 -0.14 0.64 4.91 1.0200

Comparing the two Hammett plots below, we see that removal of the dimethylamino substituent dramatically improves the fit
as measured by the value of R2.

Hammett Plot for 4-X-3,5-dimethylbenzoic Hammett Plot for 4-X-3,5-dimethylbenzoic acids

acids (-N(CH3)2 removed)
(all experimental pKa values)

log {K(X)/K(H)}
log {K(X)/K(H)}

y = 1.0504x + 0.3051 y = 1.4009x + 0.1865

R² = 0.86716 R² = 0.98475

Σ sigma 4-X Σ sigma 4-X

PS 3 2016 Solutions
5. For each of the following mechanisms, indicate if the build up of charge at reaction centre is in direct resonance
communication with substituents in the para position and specify which σ values would be used (σ, σ+, σ , or −

σorthophenols) in obtaining the susceptibility constant. Illustrate your answer with an example.
a) hydrolysis of substituted benzyl chlorides; ρ = −4.45
Cl OH
+
H2O

slow
X X X
b) addition of cyanide ion to substituted benzaldehydes; ρ = 2.55
-
O H O H HO H
CN CN
CN-
slow
X X X

Solution:

a) The reaction constant has a large negative value consistent with a substantial decrease in electron density at the transition
state, which is stabilized by electron donating groups. The magnitude of the reaction constant suggests a late transition state
with a structure similar to the carbocation intermediate. Because the positive charge is located on a benzylic carbon, it can be
resonance stabilized by substituents in the para positions. Therefore, σ+ values should be used in place of σp for those
substituents capable of electron donation by resonance. See for example, the para-methoxy substituted benzyl chloride below.

b) The reaction constant is > 0, which indicates that there is an increase in electron density in the transition state leading to the
tetrahedral intermediate. The reaction constant is reasonable large suggesting a mid- to late transition state structure. Because
the negative charge on the tetrahedral intermediate cannot be resonance stabilized onto an electron withdrawing group in the
para position, the unmodified σp values should be used in this case.

PS 3 2016 Solutions
6. a) The solvolysis of substituted diphenylcarbinyl chlorides was studied in ethanol at 25°C. A plot of log k versus
σ+ was linear with a slope of −5.1. Suggest a mechanism consistent with this observation and provide an
explanation of the ρ value in terms of the Hammond postulate.
Cl OEt

EtOH
+ HCl

X X

b) The hydrolysis of a series of ethyl benzoates by hydroxide ion in 85% aqueous ethanol has been investigated. A
Hammett plot of the second order rate constants (kB) gave a reaction constant ρ = 2.56. Calculate how much faster
ethyl 4-nitrobenzoate will undergo base catalyzed hydrolysis compared to ethyl benzoate under similar conditions.
O O

O O

O2N
X

Solution:
The Hammond postulate states that the structure of the transition state will be closest to the chemical species in an elementary
process to which it is closest in energy.

a) This is a nucleophilic substitution reaction in which ethanol is acting as a nucleophile and displacing the chloride leaving
group. The large negative ρ value (-5.51) suggests a significant decrease in electron density (build up of positive charge) at the
reaction centre of the transition state. The correlation with σ+ further indicates that the developing positive charge is in direct
conjugation with substituents in the para position. This is consistent with an SN1 type reaction mechanism in which we have a
late transition state that both structurally and energetically resembles the carbocation intermediate (Hammond postulate).

Cl
+
slow

CH3O CH3O CH3O

+

carbocation intermediate
EtOH fast

pdts

H
δ−
δ+
Cl
Ar
Ar

'late' transition state

b)
⎧ k ( NO2 ) ⎫
log ⎨ B ⎬ = ρΣσ i = 2.56(0.78) = 2.00
⎩ kB ( H ) ⎭
Therefore, kB(NO2)/kB(H) = 102.00 = 100.

In other words, the ethyl p-nitrobenzoate reacts 100. times faster than ethyl benzoate under base enhanced hydrolysis.

PS 3 2016 Solutions
7. The neutral hydrolysis of 2,4-dinitrophenyl acetate (2,4-DNPA) has a measured pseudo first order rate constant
of 4.4 x 10-5 s-1 at 22.5 oC.
a) If the reaction constant for a series of substituted phenyl acetates is determined to be ρ = 0.87, what is rate
constant for the neutral hydrolysis of the unsubstituted phenyl acetate at this temperature.
b) Suggest a substituted phenyl acetate that will have a hydrolysis half-life greater than one week.

Solution:

a) kN = 4.4 x 10-5 s-1, ρ = 0.87

⎛ k (X) ⎞
log ⎜ N(H) ⎟ = ρ Σ σ
⎝ kN ⎠

∴ log kN(H) = log kN(X) - ρ Σ σ = log (4.4 x 10-5 s-1) – 0.87 (0.78 + 1.24) = -4.36 – 1.76 = -6.12

Therefore, kN(H) = 10-6.12 = 7.6 x 10-7 s-1

b) For first order processes, t1/2 = ln 2/k, where k is a first order or pseudo first order rate constant.

So if t1/2 = 1 week = 6.05 x 105 s

Therefore,

ln 2 0.693
𝑘 < !
= = 1.1𝑥10!! 𝑠 !!
6.05𝑥10 𝑠 6.05𝑥10! 𝑠

And since,

⎛ k (X) ⎞
log ⎜ N(H) ⎟ = 0.87 Σ σ
⎝ kN ⎠

Σ σ = log (kX/kH)/0.87 = 0.18

and possible substituents include chloromethyl (-CH2Cl) and iodo (-I)

PS 3 2016 Solutions
8. The base catalyzed hydrolysis of phenyl N-phenyl carbamates occurs by the elimination of PhO- group as the
rate determining step. Estimate the second order rate constant, kB for 3,4,5-trichlorophenyl N-phenyl carbamate at
25oC using the kB values given in the Table below for other substituted phenyl N-phenyl carbamates and the
Hammett relation.
H -O
N O NH2
kB
+ OH- + CO2 +
O
X X

X kB (M-1 s-1) X kB (M-1 s-1)

p-CH3 3.0 x 101 m-Cl 1.8 x 103
p-OCH3 2.5 x 101 m-NO2 1.3 x 104
p-Cl 4.2 x 102 p-NO2 2.7 x 105

Solution:
In this question, we want to estimate the second order rate constant (kB) for hydrolysis of the trichlorocarbamate compound
below from the given data. We approach this problem by constructing a Hammett plot to determine the reaction constant (ρ)
and then the Hammett equation to calculate the rate constant assuming the substituent constants are additive (which seems to be
a good assumption in this case, see question 4 above).

N O Cl

O
Cl
Cl

⎛ k (X) ⎞
log⎜⎜ B (H) ⎟ = ρ Σσ
⎟
⎝ kB ⎠
∴ log kB(X) = ρ Σ σ + log kB(H)

So a plot of log log kB(X) versus σ, will yield a slope of ρ and an y-intercept = log kB(H).
Recognizing that the substituents are on a phenoxy group with a developing negative charge which can be delocalized onto
para-substituents, we will use σ- values where applicable (i.e., for p-OCH3 and p-NO2).

-1 -1
σ/σ − kB (M s ) log kB
p-CH3 -0.17 30 1.48
p-OCH3 -0.12 25 1.40
p-Cl 0.23 420 2.62
m-Cl 0.37 1800 3.26
m-NO2 0.71 13000 4.11
p-NO2 1.25 270000 5.43

From the plot we see that ρ= 2.90 and the Σ σ (3,4,5-trichloro) = (2(0.37) + (0.23)) = 0.97.

PS 3 2016 Solutions
 Hammett Plot for phenyl N-phenyl carbamates

6.0

5.0

4.0
log kB

3.0 y = 2.8982x + 1.9533

2.0 R2 = 0.9896

1.0

0.0
-0.5 0 0.5 1 1.5
sigma

So, log kB(H) = 1.95

and

ρ Σ σ = 2.90 (0.97) = 2.81

Therefore log kB(3,4,5-TCP) = 4.76

and

kB(3,4,5-TCP) = 5.79 x 104 M-1 s-1

PS 3 2016 Solutions
Table 1: Hammett constants for some common substituents
Substituent σ meta σ para σ- σ+ σ ophenols
CH3 -0.07 -0.17 -0.31 -0.13
Ph (C6H5) 0.06 0.01
Cl 0.37 0.23 0.11 0.68
Br 0.39 0.23 0.26 0.15 0.70
I 0.35 0.18 0.13 0.63
OH 0.10 -0.37 -0.92
OCH3 0.12 -0.27 -0.12 -0.78 0.0
NO2 0.71 0.78 1.25 0.79 1.24
CN 0.56 0.66 0.89 0.66
CO2CH3 0.33 0.45 0.66
OCOCH3 0.36 0.31
NH2 -0.16 -0.66 -1.3
N(CH3)2 -0.15 -0.83
Note: σ- and σ + apply to para substituted groups only

Table 2: Reaction and acidity constants for aromatic acids in water at 25oC
Acid ρ pKaH
Benzoic acid 1.00 4.19
Phenol 2.25 9.92
Phenoxy acetic acid 0.30 3.17
2-chlorophenoxy acetic acid 0.30 3.05
Conjugate acid of aniline 2.89 4.63

PS 3 2016 Solutions