-1-
GENERAL ORGANIC MECHANISMS NOTES
Acids & Bases
Strengths of H-A are expressed on the pKa scale, where pKa = - log10 Ka. In order to
have a unified scale for H-A and B strength, the acid strength of BH+ rather than base
strength of B is usually listed. If required, the latter value is easily calculated from the
former.
As acid strength increases, Ka increases, pKa decreases. As the base strength of B
increases Kb increases and pKa (of BH+) increases.
Some pKa’s:
Acid pKa pKa of BH+
HCl -7
CCl3CO2H 0.9
ClCH2CO2H 2.8
PhCO2H 4.2
MeCO2H 4.8
O2N-Ph-CO2H 7.2
CH3COCH2COCH3 9
HCN 9.2
PhOH 10
CH2(CO2Et)2 13
Neutral
H2O 15.7
MeCHO 17
EtOH 18
Base
O2N-Ph-NH2 19 1.0
Me2CO 20
PhNH2 ~27 4.6
Pyridine 5.3
NH3 ~36 9.2
MeNH2 ~37 10.4
Piperidine 11.2
-
OH 15.7
CH4 ~50
Factors Determining Acidity:
1) Weak A-H bond.
2) Electronegativity of A-H bond.
3) Stability of anion after H+ lost (drives equilibrium to the right), e.g. inductive or
mesomeric stabilisation of the negative charge, or lower hybridisation. Also
stereoelectronic effects, e.g. bridgeheads can prevent the molecule becoming
planar.
4) Solvation effects.
These Notes are copyright Alex Moss 2003. They may be reproduced without need for permission.
www.alchemyst.f2o.org
, -2-
Nucleophilic Substitution
1o SN2 (+ some E2)
Yes 2o SN2 & E2
3o E2
Good Nucleophile?
1o E2
No 2o E2
Yes
3o E2
Strong Base?
No 1o SN2 (no E2)
Yes 2o SN2 (little E2)
3o slow E2, SN1 and E1
possible if ionising solvent
Good Nucleophile?
1o no reaction
Ionising Yes
No 2o slow SN1
solvent? 3o SN1, E1
No
No Reaction
Eliminations
Stereoelectronics of transition state:
E2 Reactions
Hoffmann / Saytzeff Ratio increases as:
(i) Strength of B increases.
(ii) Electron withdrawal of L increases.
(iii) L- becomes a poorer leaving group.
(iv) Size of B increases.
(v) Size of R or L increases.
These Notes are copyright Alex Moss 2003. They may be reproduced without need for permission.
www.alchemyst.f2o.org
GENERAL ORGANIC MECHANISMS NOTES
Acids & Bases
Strengths of H-A are expressed on the pKa scale, where pKa = - log10 Ka. In order to
have a unified scale for H-A and B strength, the acid strength of BH+ rather than base
strength of B is usually listed. If required, the latter value is easily calculated from the
former.
As acid strength increases, Ka increases, pKa decreases. As the base strength of B
increases Kb increases and pKa (of BH+) increases.
Some pKa’s:
Acid pKa pKa of BH+
HCl -7
CCl3CO2H 0.9
ClCH2CO2H 2.8
PhCO2H 4.2
MeCO2H 4.8
O2N-Ph-CO2H 7.2
CH3COCH2COCH3 9
HCN 9.2
PhOH 10
CH2(CO2Et)2 13
Neutral
H2O 15.7
MeCHO 17
EtOH 18
Base
O2N-Ph-NH2 19 1.0
Me2CO 20
PhNH2 ~27 4.6
Pyridine 5.3
NH3 ~36 9.2
MeNH2 ~37 10.4
Piperidine 11.2
-
OH 15.7
CH4 ~50
Factors Determining Acidity:
1) Weak A-H bond.
2) Electronegativity of A-H bond.
3) Stability of anion after H+ lost (drives equilibrium to the right), e.g. inductive or
mesomeric stabilisation of the negative charge, or lower hybridisation. Also
stereoelectronic effects, e.g. bridgeheads can prevent the molecule becoming
planar.
4) Solvation effects.
These Notes are copyright Alex Moss 2003. They may be reproduced without need for permission.
www.alchemyst.f2o.org
, -2-
Nucleophilic Substitution
1o SN2 (+ some E2)
Yes 2o SN2 & E2
3o E2
Good Nucleophile?
1o E2
No 2o E2
Yes
3o E2
Strong Base?
No 1o SN2 (no E2)
Yes 2o SN2 (little E2)
3o slow E2, SN1 and E1
possible if ionising solvent
Good Nucleophile?
1o no reaction
Ionising Yes
No 2o slow SN1
solvent? 3o SN1, E1
No
No Reaction
Eliminations
Stereoelectronics of transition state:
E2 Reactions
Hoffmann / Saytzeff Ratio increases as:
(i) Strength of B increases.
(ii) Electron withdrawal of L increases.
(iii) L- becomes a poorer leaving group.
(iv) Size of B increases.
(v) Size of R or L increases.
These Notes are copyright Alex Moss 2003. They may be reproduced without need for permission.
www.alchemyst.f2o.org
