MONOPEROXYSULFURIC ACID

1

Monoperoxysulfuric Acid

1

H

2

SO

5

[7722-86-3]

H

2

O

5

S

(MW 114.07)

InChI = 1/H2O5S/c1-5-6(2,3)4/h1H,(H,2,3,4)/f/h2H
InChIKey = FHHJDRFHHWUPDG-QEZKKOIZCO

(strong oxidizing agent for many functional groups;

1

can se-

lectively oxidize amines;

2

in alcohol solvent can directly con-

vert conjugated aldehydes to esters;

3

can effect regioselective

Baeyer–Villiger oxidations;

4

can promote regioselective oxida-

tive rearrangement of tertiary alcohols to ω-hydroxy ketones

5

)

Alternate Name:

Caro’s acid.

Physical Data:

mp 45

◦

C.

Solubility:

sol water (see also Potassium Monoperoxysulfate

(Oxone)).

1c,d

Analysis of Reagent Purity:

a spectrophotometric method is

available for analysis of the components of an H

2

SO

5

/H

2

S

2

O

8

/

H

2

O

2

mixture.

6

Preparative Methods:

prepared as needed from K

2

S

2

O

8

(see

Ammonium Peroxydisulfate), concentrated Sulfuric Acid, and
water;

1b,e,f

or Hydrogen Peroxide (60–90%) and concentrated

H

2

SO

4

.

3

Handling, Storage, and Precautions:

may react explosively with

acetone, and primary or secondary alcohols.

Selective Oxidations. Neutralized Caro’s acid can chemose-

lectively oxidize arylamines to nitroso compounds (eq 1);

1b,2a,7

a simpler procedure for this transformation uses Acetic Acid/
Hydrogen Peroxide 30%.

2b

An alternative pathway leading to

the formation of azoxybenzenes (eq 1);

7

or nitro compounds

(eq 2)

8

is also possible and depends upon substrate, solvent,

pH, and reaction conditions. Caro’s acid oxidation of polyhalodi-
azines is unfruitful, except for pyrazines. While chloropyrazines
and chloroquinoxalines react with 30% H

2

O

2

in glacial acetic

acid to give mono-N-oxides with selective N-4 oxidation,

9

Caro’s

acid affords mono-N-oxides with regioselective oxidation at N-1
(eq 3).

NO

2

AcHN

NH

2

NO

2

AcHN

NO

N

+

N

–

O

AcHN

NO

2

NHAc

NO

2

Caro's acid

K

2

CO

3

, pH 7

H

2

SO

5

H

2

SO

4

50%

(1)

dioxane

56%

N

+

NH

2

O

–

N

+

NO

2

O

–

(2)

25 °C, 96 h

54%

H

2

SO

5

(3)

K

2

S

2

O

8

30% H

2

O

2

N

N

Cl

N

N

+

Cl

N

+

N

Cl

O

–

O

–

H

2

SO

4

40%

AcOH

42%

Conjugated aldehydes can be oxidized directly to α,β-un-

saturated esters by Caro’s acid in alcoholic media (eq 4).

3

The

reaction probably proceeds through a hemiacetal and not the car-
boxylic acid.

(4)

CHO

CO

2

Me

(NH

4

)

2

S

2

O

8

85% H

2

SO

4

, MeOH

86%

Baeyer–Villiger Oxidation. Caro’s acid has proven useful in

the Baeyer–Villiger oxidation of cyclic ketones and steroids.

4

The

regioselective Baeyer–Villiger oxidation of isatins to 2,3-dioxo-
1,4-benzoxazines observed with Caro’s acid contrasts sharply with
formation of isatoic anhydrides using Peracetic Acid (eq 5).

4a

The

related buffered reagent Bis(trimethylsilyl) Monoperoxysulfate is
a strong Baeyer–Villiger oxidant. This aprotic reagent is soluble
in methylene chloride and generally gives higher yields and purer
product than Caro’s acid.

10

N
H

O

O

Cl

Cl

N
H

O

N
H

O

Cl

Cl

Cl

Cl

O

O

O

O

(5)

K

2

S

2

O

8

30% H

2

O

2

H

2

SO

4

95%

AcOH, H

2

SO

4

90%

Alkyl Hydroperoxide Synthesis and Rearrangement.

Caro’s acid oxidizes tertiary alcohols to hydroperoxides, which
rearrange in the acid medium. The procedure is useful for the
conversion of cycloalkanols to ω-hydroxy ketones (eq 6).

5

Cyclic

ω

-hydroxy ketones exist as oxonium ions in sulfuric acid and thus

are resistant to further Baeyer–Villiger oxidation.

OH

O

OH

K

2

S

2

O

8

(6)

H

2

SO

4

90%

1.

(a) Fieser & Fieser 1967, 1, 118. (b) Fieser & Fieser 1977, 6, 97.
(c) Kirk-Othmer Encyclopedia of Chemical Technology, 3rd ed.; Wiley:
New York, 1983; Vol. 17, p 14. (d) Kennedy, R. J.; Stock, A. M., J.
Org. Chem. 1960

, 25, 1901. (e) Langley, W. D., Org. Synth., Coll. Vol.

1955, 3, 334. (f) Nielsen, A. T.; Atkins, R. L.; Norris, W. P.; Coon, C.
L.; Sitzmann, M. E., J. Org. Chem. 1980, 45, 2341.

Avoid Skin Contact with All Reagents

2

MONOPEROXYSULFURIC ACID

2.

(a) Coombes, R. G. In Comprehensive Organic Chemistry; Barton, D.
H. R., Ed.; Pergamon: Oxford, 1979; Vol. 3, p 305. (b) Holmes, R. R.;
Bayer, R. P., J. Am. Chem. Soc. 1960, 82, 3454.

3.

Nishihara, A.; Kubota, I., J. Org. Chem. 1968, 33, 2525.

4.

(a) Reissenweber, G.; Mangold, D., Angew. Chem., Int. Ed. Engl. 1980,
19

, 222. (b) Krow, G. R., Org. React. 1993, 43, 251. (c) Hassall, C. H.,

Org. React. 1957

, 9, 73.

5.

Deno, N. C.; Billups, W. E.; Kramer, K. E.; Lastomirsky, R. R., J. Org.
Chem. 1970

, 35, 3080.

6.

Mariano, M. H., Anal. Chem. 1968, 40, 1662.

7.

Atkinson, C. M.; Brown, C. W.; McIntyre, J.; Simpson, J. C. E., J. Chem.
Soc. 1954

, 2023.

8.

Johnson, R. M., J. Chem. Soc. (B) 1966, 1058.

9.

Mixan, C. E.; Pews, R. G., J. Org. Chem. 1977, 42, 1869.

10.

Adam, W.; Rodriguez, A., J. Org. Chem. 1979, 44, 4969.

Grant R. Krow

Temple University, Philadelphia, PA, USA

A list of General Abbreviations appears on the front Endpapers