D.H. Ripin, D.A.

Evans
Substrate

pKa's of Inorganic and Oxo-Acids

pKa H2O (DMSO)

H3O
H2S
HBr
HCl

15.7

(32)

-1.7

O
X

7.00
-9.00 (0.9)
-8.0

(1.8)
(15)

X= CH3
CH2NO2
CH2F
CH2Cl
CH2Br
CH2I
CHCl2
CCl3
CF3
H
HO

3.17

HOCl

7.5

HClO4

-10

HCN

9.4

(12.9)

HN3

4.72

(7.9)

HSCN

4.00

C6H5
o-O2NC6H4

H2SO3

1.9, 7.21

m-O2NC6H4

-3.0, 1.99

HNO3

2.12, 7.21,
12.32
-1.3

HNO2

3.29

H2CrO4

-0.98, 6.50

CH3SO3H

-2.6

(1.6)

CF3SO3H

-14

(0.3)

H3PO4

4.76 (12.3)
1.68
2.66
2.86
2.86
3.12
1.29
0.65
-0.25
3.77
3.6, 10.3
4.2 (11.1)

MeOH
i-PrOH

15.7 (31.2)
15.54 (27.9)
16.5 (29.3)

t-BuOH

17

c-hex3COH

24

CF3CH2OH

12.5 (23.5)

2.17
2.45

8.35

p-O2NC6H4OH

7.14 (10.8)

p-OMeC6H4OH

10.20 (19.1)

OH

-7.8
OH

-6.2
Ph

CH3
H
O+

Ph

H
Me

(17.1)

2.94

m-ClC6H4

3.83

p-ClC6H4

3.99

Ph

o-(CH3)3N C6H4 1.37

p-(CH3)3N+C6H4 3.43

N
O H

Ph

N
Ph

Me

OH

B(OH)3

4.25
3.02, 4.38

HOOH

11.6

cis-CO2H

1.92, 6.23

O+

-2.2

-1.8
Me

O
OH

8.88 (13.7)
(NH)

OH

(18.5)

N+ OH

0.79

SULFINIC & SULFONIC ACIDS

Me

O
Me

R= H
trans-CO2H

-2.05

Me

Ph

OH

9.23

O+ H
H

OH

PEROXIDES

9.24

-3.8
Me

11.3 (20.1)

NH4Cl

-6.5
Me

O+

OXIMES & HYDROXAMIC ACIDS

o-ClC6H4

4.47

OH

m-O2NC6H4OH

3.44

-12.4
OH

9.95 (18.0)

p-O2NC6H4

p-OMeC6H4

N+

Ph

Ph

C6H5OH

2-napthol

pKa H2O (DMSO)

(29.4)

(17.9)

(CF3)2CHOH

Substrate

PROTONATED SPECIES

ALCOHOLS

pKa H2O (DMSO)

Substrate

HOH
OH

HF

H2SO4

H2O (DMSO)

CARBOXYLIC ACIDS

INORGANIC ACIDS
H2O

pKa

Substrate

Chem 206

MeOOH

11.5

CH3CO3H

8.2

O
S

-2.6
OH

O
Ph

2.1
OH

*Values <0 for H2O and DMSO, and values >14 for water and >35 for DMSO were extrapolated using various methods.

D.H. Ripin, D.A. Evans

pKa H2O

Substrate

(DMSO) Substrate

PROTONATED NITROGEN
N+H4

9.2

EtN+H3

10.6

(10.5)

i-Pr2N H2

11.05

Et3N+H

10.75 (9.00)

PhN H3

4.6

(3.6)

PhN+(Me)2H

5.20

(2.50)

N+ H

Quinuclidine
Morpholine

11.0

Me
Me

(9.80)

H2N

NH
O

7.38

NO2
+

O2N

NH3

-9.3

NO2
N+ H

DABCO

N+

NH2 (urea)
OEt

6.90, 9.95

NH3
+NH

Proton Sponge

Et

+NH

-9.0, 12.0
(--, 7.50)

N
H

PhCN H

(21.6)

Ph

NH2

R= Me
Ph

(17.9)

PROTONATED HETEROCYCLES

(17.3)
(15.0)

DBU

MeSO2NH2

(17.5)

PhSO2NH2

(16.1)
6.3

MeSO2NHPh

(12.9)

GUANIDINIUM,
HYRDAZONES,- IDES, & -INES

Me2N

NMe2

NNH2

N
H

DMAP
+

Me2N

(21.6)

NH
HN

R= H (PPTS)
t-Bu
Me
Cl, H

5.21
4.95
6.75
0.72

(3.4)
(0.90)
(4.46)

HETEROCYCLES
H
N

NHNH2

(20.95)

PhSO2NHNH2

(17.2)

PhNHNHPh

(26.1)
NH

HYDROXAMIC ACID

(23.0)

N
HN

(18.6)

1,2,3 triazole

8.88 (13.7)
(NH)

(17.0) N
N
O
N
-10
Bn
H
*Values <0 for H2O and DMSO, and values >14 for water and >35 for DMSO were extrapolated using various methods.
Ph

6.95

(18.9)

NH

9.2

NH

O
Ph

NH

Me

Ph

(12) (estimate)
+

(9.7)

12 (20.5)
O

(14.7)

SULFONAMIDE

(24.1)
NH

(23.5)
15.1 (25.5)
(23.3)
(17.2)
(26.9)
(24.8)

O
+

NH

(13.6)

NH2

R= H
CH3
Ph
CF3

H
H3N+

NSO2Ph

N+H2

2.97, 8.82
(2.97, 8.93)

AMIDINES

Ac2NH

N-Me morpholine

8.30

pKa H2O (DMSO)

Substrate

CF3SO2NH2
(26.5)

AMIDES & CARBAMATES

N+H2 8.36

(37)

NH

TMP

(44)

Me
Me

5.96

HON H3

(7.9)
(41)

38
(36 THF))
26(THF) (30)
(30.6)
(25.0)
(16.9)

NH

8.12

H2NN H3

pKa H2O (DMSO)

Substrate

IMIDES

4.7

HN3
NH3
i-Pr2NH
TMS2NH
PhNH2
Ph2NH
NCNH2

4.16

2-napthal-N H3

H2O (DMSO)

pKa

AMINES

0.78

Ph2N H2

Chem 206

pKa's of Nitrogen Acids

N
H

OH

NH

(13.9)

D.H. Ripin, D.A. Evans

pKa H2O (DMSO)

Substrate

pKa H2O (DMSO)

Substrate

HYDROCARBONS
O

53

(Me)2CH2

51

CH2=CH2

50

CH4

48
46

(56)

43

(44)

t-BuO

Me

EtO
O

PhH

43

PhCH3

41

(43)

33.5 (32.2)

Ph3CH

31.5 (30.6)
24
(28.8)
23

PhCCH
XC6H4CH3
X= p-CN

(20.0)

(20.4)

MeO

(15.7)

15

Et
O

i-Pr

O i-Pr

(20.9)

t-Bu O

Me

Ph

i-Pr

LiO

Ph

(26.6)
Ph

Me2N

O
SPh

(25.9)

O
N+Me3

(24.9)

O
CN

(17.2)

(18.2)

(18.0)
Me2N

Me

~36

(25.7)
Me2N

Me

19-20 (27.1)

(28.3)

n
n=

[30.2 (THF)]

Ph

X=

(26.3)

Et2N

(20.1)

Et

(26.5)
(19.8)
(18.7)
(13.3)
(15.1)

(27.7)

H2

13

(26.1)

20

(14.2)

OMe

Me2N

Me

X= H
Ph
SPh
COCH3
SO2Ph

(26.9)
Me

Me

11

MeO

(30.8)

p-COPh

Me

N+Me3

AMIDES

p-NO2

Me

(23.6)

Me
O

Ph2CH2

HCCH

Ph

EtO

O
Me

pKa H2O (DMSO)

Substrate

KETONES

24.5 (30.3)

t-BuO
O

pKa H2O (DMSO)

Substrate

ESTERS

(Me)3CH

CH2=CHCH3

Chem 206

pKa's of CH bonds in Hydrocarbons and Carbonyl Compounds

X= H
CH3
Ph
COCH3
COPh
CO2Et
CN
F
OMe
OPh
SPh
SePh
NPh2
N+Me3
NO2
SO2Ph

(24.7)
(24.4)
(17.7)
(12.7)
(13.3)
(22.7)
(10.2)
(21.6)
(22.85)
(21.1)
(16.9)
(18.6)
(20.3)
(14.6)
(7.7)
(11.4)

H
OMe
NMe2
Br
CN

(24.7)
(25.7)
(27.5)
(23.8)
(22.0)

4
5
6
7
8

(25.1)
(25.8)
(26.4)
(27.7)
(27.4)

(28.1)

(29.0)

(25.5)

(32.4)
Me

Me

*Values <0 for H2O and DMSO, and values >14 for water and >35 for DMSO were extrapolated using various methods.

pKa's of CH bonds at Nitrile, Heteroaromatic, and Sulfur Substituted Carbon

D.H. Ripin, D.A. Evans

pKa H2O (DMSO)

Substrate

X=

H
CH3
Ph
COPh
CONR2
CO2Et
CN
OPh
N+Me3
SPh
SO2Ph

(31.3)
(32.5)
(21.9)
(10.2)

11

(17.1)
(13.1)
(11.1)
(28.1)
(20.6)
(20.8)
(12.0)

MeSCH2SO2Ph

(23.4)

PhSCHPh2

(26.7)

(PhS)3CH

(22.8)

(PrS)3CH

(31.3)

Ph

Ph

(28.2)

Ph

N+
O

Ph

(26.7)

(25.2)

Ph

(30.2)

O
Ph
S

(30.0)

Ph

X= H
Ph
SOPh

(33)
(27.2)
(18.2)

O
Ph

(24.5)

CHPh2

SULFONIUM
Me3S+=O
Ph

S+

(23.0)

(18.2)
(16.3)

CH2Ph

Ph

Ph
CO2Me
CN
RSCH2CN
R= Me
Et
i-Pr
t-Bu

(30.7)
(20.8)
(19.1)
(24.3)
(24.0)
(23.6)
(22.9)

PhSCH=CHCH2SPh
(26.3)
BuSH
10-11 (17.0)
(10.3)
PhSH
7

Ph
O
Ph
O
Ph
O
Ph

O
Ph

(27.6)
(30.7)

Me

(22.3)
CHPh2
O

(24.5)

CF3

S
O

NTs
S

Me
NMe

(33)
Me
N+Me2

(14.4)

(18.8)
Me
O

(21.8)
i-Pr
O

CF3

Et

(31.1)
Me
O

(20.7)
CH2Cl

CF3

Me
NTs

(29.0)
(31.0)
(31.2)
(23.4)
(22.5)
(20.2)
(22.1)
(17.8)
(11.4)
(12.5)
(27.9)
(19.4)
(12.0)
(7.1)
(23.5)
(20.5)
(12.2)
(20.2)

O
S

O
R

R= Me
i-Pr
O

X= H
CH3
t-Bu
Ph
CH=CH2
CH=CHPh
CCH
CCPh
COPh
COMe
OPh
N+Me3
CN
NO2
SMe
SPh
SO2Ph
PPh2

SULFIMIDES & SULFOXIMINES

NTs

O
S

Ph

(35.1)
(29.0)
(29.0)

X= H
Ph
SPh

X=

(PhS)2CHPh
(30.1)

Me

S
N

Me

Me

(30.5)
S
H

SULFONES

(30.8)
(20.8)
(18.7)
(16.9)
(11.8)
(30.8)
(20.3)
(11.0)
(24.9)

Substrate pKa H2O (DMSO)

SULFOXIDES

PhSCH2X
X= Ph
CN
COCH3
COPh
NO2
SPh
SO2Ph
SO2CF3
POPh2

HETERO-AROMATICS

pKa H2O (DMSO)

Substrate

SULFIDES

NITRILES
NC

pKa H2O (DMSO)

Substrate

Chem 206

(26.6)

O
S

(32.8)
Et

(PhSO2)2CH2Me

*Values <0 for H2O and DMSO, and values >14 for water and >35 for DMSO were extrapolated using various methods.

(14.3)

D. H. Ripin, D. A. Evans

pKa's of CH bonds at Heteroatom Substituted Carbon & References

pKa H2O (DMSO)

Substrate

ETHERS
(49)

MeOCH2SO2Ph

(30.7)

PhOCH2SO2Ph

(27.9)

PhOCH2CN

(28.1)

(21.1)
Ph

-14

RNO2

MeP+H3

2.7

R= CH3
CH2Me
CHMe2
CH2Ph
CH2Bn

Et3P H
Ph3P+CH3
Ph3P+i-Pr
Ph3P+CH2COPh

9.1
(22.4)
(21.2)
(6.2)

Ph3P+CH2CN

(7.0)

PHOSPONATES &
PHOSPHINE OXIDES
(18.6)

Ph

PhSeCHPh2

(27.5)

(PhSe)2CH2

(31.3)

PhSeCH2Ph

(31.0)

PhSeCH=CHCH2SePh

(27.2)
O
Ph2P

AMMONIUM

X=
Me3N+CH2X
X= CN
SO2Ph
COPh
CO2Et
CONEt2

(17.2)
(16.7)
(16.9)
(12.2)
(16.2)
(11.8)
(7.1)
(7.7)

O2N

Ph

(27.6)

CN
CO2Et

(16.4)

Cl
SiMe3

n=

(18.6)
(26.2)
(28.8)

(26.9)

(17.8)

5
6

(16.0)
(17.9)
(15.8)

SPh
CN

IMINES
(24.9)
(16.9)

(20.6)
(19.4)
(14.6)

10

(EtO)2P

X=

DMSO:

CH2SPh
CH2SO2Ph
CH2COPh

REFERENCES

NITRO

P+H4

SELENIDES

PhSe

pKa H2O (DMSO)

Substrate

PHOSPHONIUM

CH3OPh

MeO

pKa H2O (DMSO)

Substrate

Chem 206

PHOSPHINES

(20.6)

Ph2PCH2PPh2

(29.9)

(24.9)

Ph2PCH2SO2Ph

(20.3)

Water:

Ph

(24.3)
Ph

JACS 97, 7007 (1975)

JACS 97, 7160 (1975)
JACS 97, 442 (1975)
JACS 105, 6188 (1983)
JOC 41, 1883 (1976)
JOC 41, 1885 (1976)
JOC 41, 2786 (1976)
JOC 41, 2508 (1976)
JOC 42, 1817 (1977)
JOC 42, 321 (1977)
JOC 42, 326 (1977)
JOC 43, 3113 (1978)
JOC 43, 3095 (1978)
JOC 43, 1764 (1978)
JOC 45, 3325 (1980)
JOC 45, 3305 (1980)
JOC 45, 3884 (1980)
JOC 46, 4327 (1981)
JOC 46, 632 (1981)
JOC 47, 3224 (1982)
JOC 47, 2504 (1982)
Acc. Chem. Res. 21, 456 (1988)
Unpublished results of F. Bordwell

Ph

Oxime ethers are ~ 10 pka units less

acidic than their ketone counterparts
Streitwieser, JOC 1991, 56, 1989

Advanced Org. Chem., 3rd Ed.

J. March (1985)
Unpublished results of W. P. Jencks
THF:
JACS 110, 5705 (1988)

*Values <0 for H2O and DMSO, and values >14 for water and >35 for DMSO were extrapolated using various methods.