Chapter 2 Linear Free Energy Relationship

and Kinetic Isotope Effect

Substituent Effects

• Field effects

• Inductive effects

• Resonance effects

• Polarizability effects

• Steric effects

• Solvation effects

Hammett Plots-- a general method for examining changes in

charges during a reaction.

• Sigma values

CO2H CO2

+ H

X X

= log (KX/KH)

KX

Hammett Plots

• Rho values

• When >1< the reaction under study is more sensitive to substitents than benzoic acid, and negative charge is building during the reaction.

• When 0<<1, the reaction is less sensitive to substituents than benzoic acid, but negative charge is still building

• When is equal to or close to 0, the reaction shows no substituent effects.

• When is negative, the reaction is creating positive charge.

= log (KX/KH)

= log (kX/kH)

X

O NR

Ords

X

O- +C

O

N

OH

X

O NH

R

O

Path A

Path B

rds

OH

X

O NH

R

O OHX

O

H2O

HO NH

R

O

RNH2 + CO2

Competing hydrolysis mechanisms

X

O N

O

CO2H

CO2H

H

i

R

PN

CO2H

CO2H

H

O O

iiP. Jr. Wentworth, A. Datta, S. Smith, A. Marshall, L. J. Partridge, and G. M. Blackburn, J. Am. Chem. Soc., 1997, 119, 2315

LG

X

N3

Hsol

N3

X

Sol

X

+

J. P. Richard, and W. P. Jencks, J. Am. Chem. Soc., 1982, 104, 4689.

X

OCO2CH3

C6H4X

NaCH(CO2CH3)2X

CH(CO2CH3)2

W(CO)3

X

OCO2CH3

X

CH(CO2CH3)2

W(CO)2(bpy)(OMe)

+ 2,2'-bpy

NaCH(CO2CH3)2

Allylic alkylation

i

ii

iii

v

iv

J. Lehman, and G. C. Lloyd-Jones, Tetrahedron, 1995, 8863

Kinetic Isotope Effect

• Stretching vibration

• Bending vibration

C H

C H

∞

: reduced mass