CATECHOL SULFATE

1

Catechol Sulfate

O

SO

2

O

[4074-55-9]

C

6

H

4

O

4

S

(MW 172.16)

InChI = 1/C6H4O4S/c7-11(8)9-5-3-1-2-4-6(5)10-11/h1-4H
InChIKey = ORZMSMCZBZARKY-UHFFFAOYAJ

(selective reagent for the conversion of amines to sulfamate
salts

4

and sulfamides;

9

mild reagent for sulfonation of carbon

acids

16

)

Alternate Names:

pyrocatechol cyclic sulfate; 1,3,2-benzo-

dioxathiole 2,2-dioxide.

Physical Data:

mp 35.5–36

◦

C; bp 76–78

◦

C/1.25 mmHg.

4

Solubility:

Sparingly sol water and hexane; sol most organic

solvents.

Form Supplied in:

white solid or colorless needles.

Preparative Method:

reaction of catechol with SO

2

Cl

2

.

4

Purification:

distillation and recrystallization (hexane).

Handling, Storage, and Precautions:

stable indefinitely at

ambient temp; no information available on toxicity.

The reactivity of catechol sulfate (CS) with hydroxide ion is

anomalous relative to other sulfuric acid diesters. Surprising is the
very high rate of cleavage

1

and that only S–O fission is observed.

2

X-ray crystal data suggest this unusual reactivity to be due to ring-
strain effects and a distorted nonplanar conformation.

3

Conversion of Amines to Sulfamate Salts.

Amines may

be cleanly converted to catecholyl esters of sulfamic acids on
reaction with CS.

4

These readily isolable esters may be effi-

ciently hydrolyzed on mild alkaline treatment. This two-step pro-
cess affords greater selectivity than possible with other reagents
such as ClSO

3

H and SO

3

complexes,

5

fuming H

2

SO

4

,

6

,

7

and

SO

2

Cl

2

/SbCl

5

.

8

As example of the selectivity observed with CS,

amine 1 is quantitatively converted to ester 2 which is then cleanly
hydrolyzed to sulfamate salt 3 (eq 1). In contrast, while reaction
of 1 with Me

3

N/SO

3

gives 3 directly, it is formed as a minor com-

ponent (15–20%) of a complex mixture. Ester 2 is then cleanly
converted to 3 by reaction with alkali.

R-NH

2

OH

NHR

SO

2

O

OH

OH

O

OH

OMe

O

RNHSO

3

K

(1)

(2)

CS

Et

3

N, DMF

(3)

R =

(1)

0 °C, 1 h

100%

100 °C, 1 h

89%

KOH

H

2

O

The CS sulfamation procedure is limited to primary aliphatic

amines. Aromatic amines react only slowly with CS and secondary
amine/CS condensation products are not cleaved by alkali.

Conversion of Amines to Sulfamides. Catecholyl sulfamate

esters, which are available as described above, may be combined
with a second amine to provide sulfamides.

9

Other known pro-

cedures for sulfamide preparation employ strongly electrophilic
agents such as SO

2

Cl

2

.

10

–

13

The two-step CS procedure is ad-

vantaged in its selectivity and in that either symmetrical or un-
symmetrical sulfamides may be obtained. It is limited in that the
amine which reacts with CS must be primary and thus tetrasubsti-
tuted products cannot be obtained directly. Sulfamides of the type
R

1

R

2

NSO

2

NH

2

have been prepared by using a primary amine in

which the alkyl substituent is acid labile (e.g. 4-MeOPhCH

2

).

14

Exemplary of the two-step CS sulfamide methodology is the
preparation of 4 (eq 2).

1. CS, Et

3

N, CH

2

Cl

2

0 °C, 1 h

89%

(2)

(4)

NHBn

SO

2

Et

2

N

BnNH

2

2. HNEt

2

, dioxane

100 °C, 2 h

96%

Conversion of Carbon Acids to Sulfonate Salts. Reaction

of a carbanion with CS yields the catecholyl ester of a sulfonic
acid. The ester is easily hydrolyzed with alkali to give the desired
sulfonic acid salt.

15

This procedure is selective and the interme-

diate esters may easily be isolated in pure form. Carbon acids
may also be sulfonated by SO

3

and various of its complexes.

16

However, the yields are generally low and the desired products
difficult to obtain in pure form. Exemplary of CS sulfonation is
the preparation of substituted methionic acid 5 (eq 3).

15

O

SO

2

RCOO

KO

3

S

S
O

2

O

HO

O

SO

2

S
O

2

O

HO

O-

β-

D

-Glu-2-O-

β-

D

-Glu

H

H

RCOO

KO

3

S

SO

3

K

R =

(3)

(5)

n

-BuLi , CS

25 °C, 24 h

49%

THF, –78 °C

40%

100 °C, 8 h

60%

KOH

H

2

O

RCOOK

DMF

Related Reagents. Chlorosulfonic Acid; Sulfur Trioxide;

Sulfuryl Chloride.

1.

Kaiser, E. T.; Katz, I. R.; Wulfers, T. F., J. Am. Chem. Soc. 1965, 87,
3781.

2.

Kaiser, E. T.; Zaborsky, O. R., J. Am. Chem. Soc. 1968, 90, 4626.

3.

Boer, F. P.; Flynn, J. J., J. Am. Chem. Soc. 1969, 91, 6604.

4.

DuBois, G. E.; Stephenson, R. A., J. Org. Chem. 1980, 45, 5371.

5.

Gilbert, E. E. Sulfonation and Related Reactions; Interscience: New
York, 1965; Chapter 7.

6.

Bieber, T., J. Am. Chem. Soc. 1953, 75, 1405.

Avoid Skin Contact with All Reagents

2

CATECHOL SULFATE

7.

Bieber, T., J. Am. Chem. Soc. 1953, 75, 1409.

8.

Weiss, G.; Schulze, G., Justus Liebigs Ann. Chem. LA 1969, 729, 40.

9.

DuBois, G. E., J. Org. Chem. 1980, 45, 5373.

10.

Dorlars, A., Methoden Org. Chem. (Honben-Weyl) 1958, XI/2, p 711.

11.

Andersen, K. K. In Comprehensive Organic Chemistry, Barton, D. H.
R., Ollis, W. D., Eds.; Pergamon: New York, 1979; Vol. 3, p 363.

12.

Spillane, W. J., Int. J. Sulfur Chem., Part B 1973, 8, 469.

13.

Gilbert, E. E. Sulfonation and Related Reactions, Interscience: New
York, 1965; Chapter 7.

14.

Lee, C.-H.; Lee, M. S.; Lee, Y.-H.; Chung, B. Y., Bull. Korean Chem.
Soc. 1992

, 13, 357.

15.

DuBois, G. E.; Stephenson, R. A., J. Med. Chem. 1985, 28, 93.

16.

Gilbert, E. E. Sulfonation and Related Reactions, Interscience: New
York, 1965; p 33.

Grant E. DuBois

The Coca-Cola Company, Atlanta, GA, USA

A list of General Abbreviations appears on the front Endpapers