Hammett Correlations and Their Applications in

Elucidating Reaction Mechanism

Stoltz Group Literature Seminar

Eric Ferreira
July 17, 2003 at 12pm

Ph Ph

OH2 NH2
N H HN
k1 k2 O
Yn
Yn Yn Ph H

3.3

3.2 m-OMe

unsub p-Cl
3.1
m-Cl
3

p-Me m-Me
log kob s 2.9

2.8 m-NO2

2.7
p-OMe
2.6

2.5
-0.4 -0.2 0 0.2 0.4 0.6 0.8
!

Outline & References

Outline:
- The development of the Hammett equation

- Significance of ! and "

- Cationic and anionic cases

- Substantial deviations from correlations

- More sophisticated models for quantitative analysis

- Mechanism of organometallic reactions

Key References:
Isaacs, N. Physical Organic Chemistry; Wiley: New York, 1995; Ch. 4.

Hansch, C.; Leo, A.; Taft, R. W. Chem. Rev. 1991, 91, 165. (tons of values)

Jaffe, H. H. Chem. Rev. 1953, 53, 191.

Lowry, T. H.; Schuller Richardson, K. Mechanism and Theory in Organic Chemistry; Harper and Row: New York, 1987;
pp 143-159.

Exner, O. The Hammett Equation. In Advances in Linear Free Energy Relationships; Chapman, N. B. and Shorter, J.,
Eds.; Plenum Press: London, 1972; Ch. 1.

March, J. Advanced Organic Chemistry; Wiley: New York, 2001; pp 368-375.

2
 The First Designation of Substituent Constants
O O
H H
KA
O O H H
O O
H 25 °C
Y H
Y
electrophile nucleophile

Y KA pKA log KA !

NO2 3.55 x 10-4 3.45 -3.45 0.75

CN 2.75 x 10-4 3.56 -3.56 0.64 ! = log (KY /K0 )

= log KY - log K0
Cl 1.00 x 10-4 4.00 -4.00 0.20

H 6.31 x 10-5 4.20 -4.20 0.00 KY : substituted acid

K0 : unsubstituted acid
Me 4.27 x 10-5 4.37 -4.37 -0.17

OMe 3.39 x 10-5 4.47 -4.47 -0.27

- Numbers tabulated for a variety of meta (!m ) and para (!p ) substituted benzoic acids

- Positive ! values describe electron-withdrawing groups (weakens OH bond) Hammett, L . P.

Chem. Rev.
1935, 17, 125.
- Negative ! values describe electron-donating groups (strengthens OH bond)

The Hammett Equation

Key principle: All reactions that correlate to the Hammett equation

will use the same set of substituent constants. That is, a structural
modification will produce a proportional change in reaction rate
based on the " values.
Hammett Equation:

kY Changes in structure produce proportional changes in !G‡ .

log = !"
k0
This is necessary because -!G = RT ln k = 2.303RT log k

kY : rate of reaction for substituted benzene ring Therefore, this is a LINEAR FREE ENERGY RELATIONSHIP.

k0: rate of reaction for unsubstituted benzene ring

!: reaction constant Remember: !G‡ = !H‡ - T!S‡

": substituent constant Since the relationship between free energy and !" is linear (for all
reactions run at constant T), !H‡ and !S‡ cannot be independent.
(One consequence: ortho-substitution cannot obey the Hammett
equation due to highly variable entropies from reaction to reaction.)

" !
- Measurement of capacity to perturb electronic - Measurement of sensitivity of reaction to electronic
environment perturbation

- First values described by Hammett - Individual for each reaction

- Referenced to hydrogen substituent (0.00) - Referenced to equilibrium of benzoic acids in water

at 25 °C (1.00)
- Over the next 20 years, values averaged over several
series of reactions to give good correlations for all - Magnitude and sign can be diagnostic of reaction
mechanism

3
 A Simple Example: Basic Hydrolysis of Esters

O O
-
OEt OH , k O EtOH

Y Y

Y ! k (M-1 s-1 )
2.5

NO 2 0.78 32.9 p-NO2

2
" = 2.54
p-CN
CN 0.71 15.7
1.5

Cl 0.24 2.10 kY 1
log p-Cl
kH
H 0.00 0.289 0.5

Me -0.14 0.172 0 unsub

p-OMe
p-Me
OMe -0.27 0.143 -0.5
-0.4 -0.2 0 0.2 0.4 0.6 0.8 1
!
(! values readjusted to more recent average
relative to benzoic acid equilibria) Value of " (>1) tells that reaction is more susceptible to
electronic perturbation

Consistent with mechanism of hydroxide ion attack at

Hammett, L. P. Chem. Rev. 1935, 17, 125. carbonyl center

Some Basic Math

m: slope
y = mx + b
b: y-intercept
16

Logarithm Rules: 14

log (xy) = log x + log y 12

log x = log x - log y 10

y
8

4 y = 2x + 3
2
(m = 2, b = 3)
0
0 1 2 3 4 5 6 7

In the context of the Hammett Equation...

": x-variable
kY Most people will plot " vs. log (kY /k0).
log = !"
k0 log kY : y-variable
Therefore, the y-intercept is meaningless,
= log kY - log k0 log k0 : y-intercept and only the slope of the line will give
information.
log kY = !" + log k0 !: slope

4
 What Contributes to !?

Resonance effects Inductive effects

Classical inductive
effect (through-bond)
"#

"+ NMe3

""+
"#
MeO O MeO O
Field effect
"# (through-space)

Through-bond evidence:

OMe (CH2)n NMe3

O n 0 1 2 3

cannot be stabilized !m 1.04 0.4 0.16 0.06

by resonance
!p 0.88 0.44 0.13 0.02

Through-space evidence:

Me2 N NMe2
Electron-withdrawing groups: +! deuterates
(H2C)2 (CH2)2 105 slower
Electron-donating groups: #! than

Sign of " can be Diagnostic of Mechanism

O O
H , H2 O
OR OH
Yn Yn ROH

AA1 mechanism AAc mechanism

O O
Ar Electrons going toward Ar Electrons going away
O aromatic ring from aromatic ring
O
H H
Increased by EWG (+!) Increased by EDG (-!)

R = Me
R = i-Pr 65 °C in 100% H2 SO4
0 °C in 98.7% H2SO 4 with H[B(HSO4 )4 ]
0 -2

" = 1.99 4-Cl,3-NO2 -2.2 " = -0.825

-0.5 3-NO2 -2.4
4-NO2 4-NO2
-2.6
3-Me,4-NO2 3-NO2
-1
4-Me,3-NO2 -2.8
4-Cl,3-NO2
log k log k -3
3,4-NO2
-1.5 -3.2
3,5-NO2
-3.4
4-Cl
-2 -3.6
unsub
-3.8

-2.5 -4
0 0.2 0.4 0.6 0.8 1 0 0.2 0.4 0.6 0.8 1 1.2 1.4 1.6
! !
Hopkinson, A. C. J. Chem. Soc. B 1969, 203.

5
 Magnitude of ! Value can be Important

5
! = 1.26
p-NO2
O O 4.5

NaOH, H2 O
OMe OH 4 p-Br
125 °C
Y Y log k125° 3.5

p-NH2 unsub
3 p-Me

2.5

2
-1 -0.5 0 0.5 1

Recall:
"
Hypothesis:
O O
O
OH
OEt OH
O OH
Y Y
! = 2.54 Y
Smaller ! value, therefore electronic effect
consistent with: O is more removed from benzene ring.

OEt 18
O studies confirmed mechanism

Y
(Note ortho-substitution--ok for comparison
OH
purposes only!)

Goering, H. L.; Rubin, T.; Newman, M. S. J. Am. Chem. Soc. 1954, 76, 787.

Magnitude of ! can be Important (other cases)

O O
!
KA water, 25 °C 1.00
OH O
Yn H2O Yn H3O 50% aq. EtOH 1.52

sensitive to rxn conditions

(solvent, temperature, etc.)

Ionization of acids in water at 25 °C:

O O
OH
OH Yn OH
Yn O Yn

! = 1.00 ! = 0.562 ! = 0.212

O O

OH OH
Yn Yn

! = 0.466 ! = 0.256
(transmission thru (transmission thru 2
"-system better) pathways better than 1)

6
 Magnitude of ! can be Important (other cases-compensating effects)

O O

NH2 H H2O OH NH3 ! = 0.12

Yn Yn

Pre-equlibrium protonation makes negative contribution to !, but nucleophilic attack makes a

positive contribution. Two effects cancel each other out.

Br OH
Yn OH Yn Br ! = -0.33

Attack of hydroxide facilitated by EWG, but bromide leaving facilitated by EDG. Effects cancel,
leaving a small reaction constant.

I
Yn EtO Yn EtOH I ! = 2.07

Deprotonation assisted by EWG, but iodide leaving assisted by EDG. However, compensating
effect of halide release is small due to more remote positioning.

Initial Hammett Values Inadequate for Some Reactions

Cl 90% aq. acetone OH

Yn H2O Yn HCl
25 °C

via:
Correlations are not that good,
Yn especially with para substitution

meta-substitution para-substitution
-3 0
OMe
-3.5 Me
-1 SMe
unsub
t-Bu SMe
-4
-2
Me
-4.5 OMe
-3 t-Bu F
-5
log k CO2Me
log k -4
unsub
-5.5 F Cl
Cl Br -5 Br
-6
CN -6
-6.5 CF3
NO2 CO2Me CN
-7 -7 CF3 NO2
-7.5 -8
-0.2 0 0.2 0.4 0.6 0.8 -0.4 -0.2 0 0.2 0.4 0.6 0.8 1
! !

Stock, L. M.; Brown, H. C. Adv. Phys. Org. Chem. 1963, 1, 35.

7
 Brown Introduces !+

Cl 90% aq. acetone OH

Yn H2O Yn HCl
25 °C

Brown's modification of Applied to reactions where a cation or near-cation is developed

the Hammett Equation:
Meta values relatively close to Hammett ! values
kY
log = " +! +
k0 Para values for EDG differ greatly from Hammett ! values
due to resonance stabilization

meta-substitution " + = -4.54 para-substitution

-3 0
OMe
-3.5 Me t-Bu -1 SMe
unsub
-4 OMe -2 Me
-4.5 SMe
-3 t-Bu F
-5 unsub
log k -4 Cl
-5.5 CO2Me log k Br
F Br -5
-6 Cl CF 3
CN CO2Me
-6
-6.5 CF3
NO2 CN
-7 -7
NO2
-7.5 -8
-0.2 0 0.2 0.4 0.6 0.8 -1 -0.5 0 0.5 1
!m + !p +
Values are calculated from this reaction, but several reactions correlate well with these numbers.
Brown, H. C.; Okamoto, Y. J. Am. Chem. Soc. 1957, 79, 1913.
Stock, L. M.; Brown, H. C. Adv. Phys. Org. Chem. 1963, 1, 35.

!+ Applications

O
Benzylic alcohol oxidation:
S NHCl
O
O
OH CAB, HClO 4
Yn H Chloramine B (CAB)
Yn
50% aq. AcOH
25 °C

correlation with ! correlation with !+

0 0
-0.5 -0.5 " + = -2.14
-1 p-OMe -1 p-OMe
-1.5 -1.5
-2 -2
log k -2.5 -2.5
log k
-3 -3
-3.5 -3.5
-4 -4
-4.5 -4.5
-5 -5
-0.4 -0.2 0 0.2 0.4 0.6 0.8 1 -1 -0.5 0 0.5 1
! !+
Mechanism thus proposed involves cationic intermediate:

OH
slow OH OH
Ar H Cl NHSO2 Ph
H Ar Ar H

Mukherjee, J.; Banerji, K. K. J. Chem. Soc., Perkin Trans. 2 1980, 676.

8
 !+ Applications

O
H dimethylketene,
AlCl3
Yn CHMe2 " + = -6.6
Yn

Dramatic effects and high correlations can be seen when reaction center is on ring.

HBR2 BR2
Yn " + = -0.49
Yn

EDG will accelerate attack on boron, while EWG will facilitate hydride addition at the benzylic carbon. Effects
will cancel each other out.

N
N N N
N3
N3 Yn " + = 3.7
Yn

Positive reaction constant due to cationic intermediate in the reactant rather than the product.

What About Anions?

NH2
Analogous modification of
the Hammett Equation for H -H
+
N
anionic centers: S
kY Yn O2 + H+
log = !- "-
k0
NH2

N
Values determined based on several S
reactions involving phenols and Yn O2
anilines (anionic in transition state).

Correlation with " Correlation with "-

-5 -5

-5.5 -5.5

-6 -6

-6.5 -6.5
p-NO2
-7 -7
p-SO2NH2 p-CN
log -7.5
log -7.5
KNH p-COMe KNH
-8 -8
-8.5 -8.5
-9 -9

-9.5 -9.5
-10 -10
-0.4 -0.2 0 0.2 0.4 0.6 0.8 1 -0.5 0 0.5 1 1.5
" "-
+
Values much closer to " values than " is to ". Only noticeable difference is in highly EWG in para positions.

Yoshioka, M.; Hamamoto, K.; Kubota, T. Bull. Chem. Soc. Jpn. 1962, 35, 1723.

9
 Reconciliation Between !, !+ , and !-: The Yukawa-Tsuno Equation

For all practical purposes, the three parameters (!, !+, and !-) are satisfactory for correlating reactions.

Attempts have been made, however, to quantify the contributions between "normal" and "enhanced" resonance effects.

The constant r expresses the degree of enhanced resonance

Yukawa-Tsuno Equation
r = 0.00 for benzoic acid hydrolysis
kY
log = "(! + r(!+ # !)) r = 1.00 for cumyl chloride hydrolysis (how !+ was defined)
kH

Analogous !- equation applied to anionic-type reactions

3
O
2

H 1
Yn Yn
log krel
H2O 0

-1
r = 0.81: value indicates a largely-developed cation
as the intermediate -2

-3
-0.8 -0.6 -0.4 -0.2 0 0.2 0.4 0.6
! + 0.81(!+ # !)

Yukawa, Y.; Tsuno, Y. Bull. Chem. Soc. Jpn. 1959, 32, 971.

Deviations from Hammett Correlations: Concave Up

Br Br
acetone N
Yn Yn
N

Two possibilites:
0.25
1) Gradual change in transition state
structure 0.2

0.15
vs. Ar N
Ar Br 0.1
kY
log 0.05
reagent-like product-like
ts ts k0
0

2) Complete change in mechanism -0.05

(e.g. SN 1 to SN 2)
-0.1
py
Ar py -0.15
Ar Br Ar
-0.2 0 0.2 0.4 0.6 0.8 1
!
solid circles: meta substituents
Br hollow circles: para substituents

Ar Ar py Note: meta and para substituents should be divided

in these situations due to their differing inductive
py and resonance contributions to reactivities.
Swain, C. G.; Langsdorf, W. P. J. Am. Chem. Soc. 1951, 73, 2813.

10
 Deviations from Hammett Correlations-Concave Down

Ph Ph

H OH2 NH2
N HN
k1 k2 O
Yn
Yn Yn Ph H

3.3

3.2 m-OMe
A concave down Hammett curve is indicative
of a change in rate determining step. unsub p-Cl
3.1
m-Cl
3

p-Me m-Me
Electron-rich groups will assist in step 1, log kob s 2.9
making step 2 rate-limiting.
2.8 m-NO2

Alternatively, electron-withdrawing groups 2.7

will ultimately increase the rate of step 2, p-OMe
making step 1 rate-determining. 2.6

2.5
-0.4 -0.2 0 0.2 0.4 0.6 0.8
!
Hoffmann, J.; Klicnar, J.; Sterba, V.; Vecera, M. Coll. Czech. Chem. Commun. 1970, 35, 1387.

Deviations from Hammett Correlations-Concave Down

Y OH k1 k2
Y OH2 Y k3
k-1 k-2 Y
X X X
X Z
Z Z Z
visible by UV visible by UV

80% aq. AcOH w/ 4% H2SO 4 at 25 °C

X,Y,Z variously substituted--! and !+ values 1
determined by simple summation of individual
values 0.5

0
Right side of plot: Ionization to carbocation
is rate limiting. Not surprising, since EWG
-0.5
cannot stabilize this structure.
log kob s
-1
Left side of plot: EDG can stabilize the
carbocation through induction and/or -1.5
resonance.
-2
Positive " + since the cation is the reactant k2 : rds
k3 : rds
(as in the aryldiazo-azide case) -2.5
-2 -1.5 -1 -0.5 0 0.5 1
!+ !

Hart, H.; Sedor, E. A. J. Am. Chem. Soc. 1967, 89, 2342.

11
 New Models for Quantitative Analysis of Substitution Patterns

Relatively unused by experimental chemists--either poor correlations across reactions or too complex to be practical

However, physical organic chemists sought to solidly divide substituents into separate resonance and inductive
components

The Taft-Ingold Equation:

kY #": substiuent constant (almost of complete inductive nature)
log = !"#"( + !s E s )
kMe Es : steric constant

O H2O O - Based on aliphatic systems

EtOH
Y Y
OEt OH - Resonance contribution essentially negligible

Wells, P. R.; Ehrenson, S.; Taft, R. W. Prog. Phys. Org. Chem. 1968, 6, 147.

Roberts-Moreland work: Swain-Lupton extension:

Defined R as the resonance substituent constant and
fit several reactions to the equation:
Measured acid dissociation kY
Y log =f F + rR
constants of structures
where resonance could not kMe
contribute: Interestingly:
HOOC
+
#m = 0.57 F + 0.14 R # = 0.34 F + 0.54 R
Defined an inductive substiuent constant: F
#p = 0.49 F + 0.30 R #- = 0.46 F + 0.66 R

Roberts, J. D.; Moreland, J. Swain, C. G.; Lupton, E. C.

J. Am. Chem. Soc. 1953, 75, 2167. J. Am. Chem. Soc. 1968, 90, 4328.

New Models for Quantitative Analysis of Substitution Patterns

The approach to developing modern "I and "R scales:

COOH
Y Y

N - All compounds should have

HOOC H KY minimal resonance contributions
Y
log = !" I
COOH KH - Found ! for each ionization
O
- Averaged to find "I
Y
OH
CH2 Y

"R P " R(BA) P O "R+ "R -

Fit reactions to equation: P

kY
log = #I "I + #R "R
kH

with one of four types of " R Y Y Y Y

where reaction occurs at
center P
No direct Weak Strong Strong
resonance interaction acceptor donor

Note: even though this equation has two variable parameters, the correlation can be displayed in a linear graph
via linear combinations.
The dual-parameter approach has been moderately effective in correlations involving ortho substituents, and
reactions through heterocyclic, olefinic, and aliphatic cores.

Refs available in Isaacs, N. Physical Organic Chemistry ; Wiley: New York, 1995; pp 175-180.

12
 Mechanistic Studies of Oxidative Addition
Previously reported:

Pd(PPh3 )4
Ph3 P Proceeds with 95%
Br Br Pd inversion
H H
Me Ph3 P Me

Lau, K. S. Y.; Wong, P. K.; Stille, J. K. J. Am. Chem. Soc. 1976, 98, 5832.

What about oxidative addition of C sp2 -X bonds with palladium catalysts?

R "nonionic"
M
X
Path 1

RX M0 R MII X

Path 2

RX MI R , MIX
"ionic"
Not to be ignored...

M
X M X
X

Nucleophilic aromatic substitution considered an "ionic" pathway, like Path 2.

At the very least, presence of charged intermediates separates it from the concerted mechanism.
Amatore, C.; Pfluger, F. Organometallics 1990, 9, 2276.

Mechanistic Studies of Oxidative Addition

Consider the equilibria:

Because K1 and K2 are equilbria
(PPh3 )4 Pd (PPh3 )3 Pd PPh3 K1 >> 1 (fast) between neutral species, they
should be relatively independent
of solvent polarity.
(PPh3 )3 Pd (PPh3 )2 Pd PPh3 K2 << 1 (slow)
As a consequence, any variation of
k activation parameters between
(PPh3 )2 Pd ArI (PPh3 )2 Pd(Ar)I
solvents is directly attributable to
the oxidative addition step.

Pd(PPh 3)4 and ArI in toluene, rt

Variations of r between solvents would be indicative of 0.8

changes in the activation parameters. (Remember LFER) " = 2.3 p-Br

0.6

" value for this reaction is nearly identical in THF. 0.4 p-Cl

This indicates that solvation of charged intermediates is 0.2

not involved in the oxidative addition step.
log krel 0
unsub
It is most consistent, therefore, with a concerted,
"nonionic" mechanism where charges are not developed -0.2 p-Me
(Path 1).
-0.4
Amatore, C.; Pfluger, F. Organometallics 1990, 9, 2276. p-OMe
-0.6
-0.3 -0.2 -0.1 0 0.1 0.2 0.3
!
Compare with an electron transfer process:
k kTHF Tsou, T. T.; Kochi, J. K.
L nNi0 ArX L nNiII (Ar)X = 8.8 J. Am. Chem. Soc.
solvent ktolu ene 1979, 101, 6319.

13
 Attempts to Explain Better Heck Catalysts via Hammett Correlations

Heck reaction mechanism for oxidative addition to anionic palladium species:

Ar2
(o-tol)3 P + OAc (o-tol)3 P reduction P
O O
Pd Pd Pd Pd
(o-tol)3 P - P(o-tol)3 AcO + H-
P O O
+ e- Ar2
catalyst 1
+ ArBr catalyst 3

(o-tol)3 P Ar (o-tol)3 P Br Ar
+ OAc
Pd Pd Pd
AcO Br Ar Br P(o-tol)3
catalyst 2

Br 2 mol % [Pd] CO2 Bu ! - for cat. 1 = 1.01

CO 2 Bu ! - for cat. 2 = 1.00
NaOAc -
R DMF, 130 °C R ! for cat. 3 = 1.58

Hypothesis:

Pd
is the intermediate doing oxidative addition. The Pd-C bond is not broken.
P
Ar2

Bohm, V. P. W.; Herrmann, W. A. Chem. Eur. J. 2001, 7, 4191.

An Atypical Ruthenium Oxidation Pathway Derived from Hammett Correlations

OH O 2+ O N N
(TMC)Ru (BF 4 )2 TMC:
Xn Yn O Xn Yn N N
CH3 CN, 40 °C
! = -1.44 1,4,8,11-tetramethyl-
1,4,8,11-tetraazacyclotetradecane

Did not correlate well with "+ values, unlike most other oxidations. Therefore, a more concerted process that
doesn't invoke an #-carbocation is likely involved.

Proposed rate-determining steps:

NOT:
2+ 2+
O O OH
HO [2+2]
(TMC)Ru CAr2 2+
(TMC)Ru CAr2 O
HO
O H
OH (TMC)Ru CAr2
or O H

2+
O 2+ O
HO
(TMC)Ru CAr2 (TMC)Ru O CHAr2
O H O H
OH +
2+ OH
O (TMC)Ru
CAr2
(TMC)Ru O CHAr2 O
OH
Wang, Z.; Chandler, W. D.; Lee, D. G. Can. J. Chem. 1998, 76, 919.

14
 Hammett Plots in the Oxidative Kinetic Resolution

O
1.7 mol % (sparteine)PdCl 2
OH 50 mol % sparteine H
Yn Yn
DCE, 1 atm O2 , 50 °C

(At high sparteine concentration, #-hydride elimination was found to be rate limiting.)
0.5 0.5
" = -1.41 ± 0.15 " + = -1.00 ± 0.13
0 0
p-OMe p-OMe
-0.5 unsub -0.5 p-Me unsub
p-Me
log kob s -1 log kob s -1
p-CF3 p-CF3
m-OMe m-OMe
-1.5 -1.5
m-F m-F
p-NO2 p-NO2
-2 -2

-2.5 -2.5
-0.4 -0.2 0 0.2 0.4 0.6 0.8 1 -1 -0.5 0 0.5 1
! !+

"The calculated " and " + values...indicate that substituents influence the rate of both induction and resonance. The
negative " value signifies a positive charge buildup in the transition state consistent with #-hydride elimination
being rate limiting at high [sparteine]. The negative " + value specifies that direct resonance donation stabilizes
the positive charge buildup at the benzylic center during rate-limiting #-hydride elimination at high [sparteine]."

Mueller, J. A.; Sigman, M. S. J. Am. Chem. Soc. 2003, 125, 7005.

Hammett Plots in the Oxidative Kinetic Resolution

Sigman's analysis is flawed! 0.5

" = -1.41 ± 0.15
0
Hammett plots should be correlated to one set p-OMe
of parameters (i.e., ! or !+), not both sets. -0.5 unsub
p-Me
Both sets account inductive and resonance effects log kob s -1
in varying degrees. p-CF3
m-OMe
-1.5
m-F
In fact, a conclusion cannot be drawn based on this p-NO2
data, because only two substituents have notably -2

different ! and !+ values.

-2.5
-0.4 -0.2 0 0.2 0.4 0.6 0.8 1
Substituent ! !+ !

p -OMe -0.27 -0.78 0.5

" + = -1.00 ± 0.13
p -Me -0.17 -0.31 0
p-OMe

-0.5 p-Me unsub

unsub 0 0

m-OMe 0.12 0.10 log kob s -1

m-OMe p-CF3

m-F 0.34 0.34 -1.5

m-F
p-NO2
p -CF3 -2
0.54 0.53
-2.5
p -NO2 0.78 0.79 -1 -0.5 0 0.5 1
!+
More data points, better accuracy, and perhaps a Yukawa-Tsuno analysis would be more appropriate.

15