PEROXYMALEIC ACID

1

Peroxymaleic Acid

1

O

O

O

H

CO

2

H

[3851-95-4]

C

4

H

4

O

5

(MW 132.08)

InChI = 1/C4H4O5/c5-3(6)1-2-4(7)9-8/h1-2,8H,(H,5,6)/b2-1-/f/

h5H

InChIKey = KFHHPVVJLXPHJL-MTLNHKJBDJ

(electrophilic reagent capable of reacting with many functional

groups; delivers oxygen to alkenes and amines

2

)

Alternate Names:

permaleic acid; PMA.

Solubility:

sol CH

2

Cl

2

, CHCl

3

and water.

Form Supplied in:

not available commercially.

Analysis of Reagent Purity:

assay using iodometry.

3

Preparative Methods:

(a) to a cooled (0

◦

C) and stirred

mixture of 90% Hydrogen Peroxide (caution!) (11.6 g,
0.34 mol) and CH

2

Cl

2

(150 mL) is added in one batch

39.2 g (0.4 mol) of freshly crushed (Maleic anhy-
dride)bis(triphenylphosphine)palladium. When the major por-
tion of the anhydride has reacted, the reaction mixture is heated
to reflux.

2

(b) 0.1 mol of 88% H

2

O

2

, 0.13 mol of maleic anhy-

dride, CHCl

3

(19.5 mL), and DMF (0.5 mL) are stirred at 20

◦

C

for 1.5 h to give the reagent, essentially free from H

2

O

2

.

4

Handling, Storage, and Precautions:

reasonably stable in

CH

2

Cl

2

solution, decomposing to the extent of 5% in 6 h at

rt. Since peroxy acids are potentially explosive, care is required
while carrying out the reactions; during workup, test for perox-
ides before solvent removal. This reagent should be handled in
a fume hood.

Baeyer–Villiger Reaction. Simple acyclic ketones and cyclic

ketones having seven or more carbon atoms in the ring do not
undergo facile Baeyer–Villiger reaction with normal peroxy acids
like m-Chloroperbenzoic Acid; only PMA and Trifluoroperacetic
Acid (TFPAA) are useful for this reaction. Although PMA is not as
powerful an oxidizing agent as TFPAA, its reactivity is adequate.
When TFPAA is used, an inorganic buffer reagent has to be added;
when PMA is used there is no need for such a buffer reagent.

2

Baeyer–Villiger reaction of the ketone (1) furnishes the ester

(2) (eq 1).

2

Oxidation of the diketone (3) furnishes the lactone

(4) in 77% yield; the reaction was performed on a 1.0 mol scale.

5

Baeyer–Villiger reaction of the ketone (5) furnished in 93% yield
the acetate (6)

6

Ketone (7) gave the acetate (8) in 90% yield;

7

this

oxidation cannot be carried out with m-CPBA.

Cyclododecanone has been oxidized to the lactone (9) (eq 2).

8

The reaction has been carried out on the 250 g scale. In this case,
PMA satisfactory for the Baeyer–Villiger reaction was prepared
with 30% H

2

O

2

by using enough Acetic Anhydride to react with

the water present.

It has been observed that reaction of maleic anhydride with 86%

H

2

O

2

in CH

2

Cl

2

is incomplete even at reflux temperature. PMA

prepared by method (b) above reacted rapidly (15–30 min) with a
slight excess of cyclohexanone at 35–40

◦

C to provide hexanolide

in 90–100% yield.

4

i

-Pr

O

O

O

i

-Pr

(1)

(2)

PMA, CH

2

Cl

2

reflux, 3 h

(1)

72%

O

O

O

O

O

(3)

(4)

(5) R = COMe

(6) R = OCOMe

R

CO

2

Me

(8) R = OCOMe

R

(7) R = COMe

O

O

O

11

30% H

2

O

2

, Ac

2

O

maleic anhydride

CH

2

Cl

2

(2)

(9)

(CH

2

)

11

77%

Oxidation of Nitrogen-containing Compounds. Aromatic

primary amines (10) and (12) have been oxidized by PMA to
the nitro compounds (11)

2

and (13)

9

in yields of 40% and 61%,

respectively. The nitro compound (11) cannot be prepared from
(10) using TFPAA.

2

R

(10) R = NH

2

(11) R = NO

2

R

(12) R = NH

2

(13) R = NO

2

Other Applications. Alkenes which are not electron rich can

be epoxidized by PMA; 1-octene and methyl methacrylate have
been epoxidized in 80% and 74% yields.

2

Adenine 1-oxide nu-

cleotides have been prepared by oxidation of natural compounds
in 75–80% yields with PMA in aqueous solution at neutral pH.

10

1.

(a) Swern, D. In Organic Peroxides; Swern, D., Ed.; Wiley: New York,
1971; 2, Chapter 5. (b) Plesnicar, B. Organic Chemistry; Academic: New
York, 1978; 5C, p 211.

2.

White, R. W.; Emmons, W. D., Tetrahedron 1962, 17, 31.

3.

Ogata, Y.; Sawaki, Y., Tetrahedron 1967, 23, 3327.

4.

Hawkins, E. G. E., J. Chem. Soc. (C) 1969, 2691.

5.

Johnson, P. Y.; Yee, J., J. Org. Chem. 1972, 37, 1058.

6.

Gopichand, Y.; Khanra, A. S.; Mitra, R. B.; Chakravarti, K. K., Indian
J. Chem. 1975

, 13, 433.

7.

Brook, P. R.; Brophy, B. V., J. Chem. Soc., Perkin Trans. 1 1985, 2509.

8.

Bidd, I.; Kelly, D. J.; Ottley, P. M.; Paynter, O. I.; Simmonds, D. J.;
Whiting, M. C., J. Chem. Soc., Perkin Trans. 1 1983, 1369.

9.

Yost, Y.; Gutmann, H. R., J. Chem. Soc. (C) 1969, 345.

10.

Mantsch, H. H.; Goia, I.; Kezdi, M.; Barzu, O.; Dansoreanu, M.;
Jebeleanu, G.; Ty, N. G., Biochemistry 1975, 14, 5593.

A. Somasekar Rao & H. Rama Mohan

Indian Institute of Chemical Technology, Hyderabad, India

Avoid Skin Contact with All Reagents