CATECHOL SULFATE 1
Catechol Sulfate 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-
O
cedures for sulfamide preparation employ strongly electrophilic
SO2
O agents such as SO2Cl2.10 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
[4074-55-9] C6H4O4S (MW 172.16)
amine which reacts with CS must be primary and thus tetrasubsti-
InChI = 1/C6H4O4S/c7-11(8)9-5-3-1-2-4-6(5)10-11/h1-4H
tuted products cannot be obtained directly. Sulfamides of the type
InChIKey = ORZMSMCZBZARKY-UHFFFAOYAJ
R1R2NSO2NH2 have been prepared by using a primary amine in
which the alkyl substituent is acid labile (e.g. 4-MeOPhCH2).14
(selective reagent for the conversion of amines to sulfamate
Exemplary of the two-step CS sulfamide methodology is the
salts4 and sulfamides;9 mild reagent for sulfonation of carbon
preparation of 4 (eq 2).
acids16)
Alternate Names: pyrocatechol cyclic sulfate; 1,3,2-benzo-
1. CS, Et3N, CH2Cl2
dioxathiole 2,2-dioxide.
0 °C, 1 h Et2N
ć% ć% SO2
89%
Physical Data: mp 35.5 36 C; bp 76 78 C/1.25 mmHg.4
(2)
BnNH2 2. HNEt2, dioxane
NHBn
Solubility: Sparingly sol water and hexane; sol most organic
100 °C, 2 h
(4)
solvents.
96%
Form Supplied in: white solid or colorless needles.
Preparative Method: reaction of catechol with SO2Cl2.4
Purification: distillation and recrystallization (hexane).
Conversion of Carbon Acids to Sulfonate Salts. Reaction
Handling, Storage, and Precautions: stable indefinitely at
of a carbanion with CS yields the catecholyl ester of a sulfonic
ambient temp; no information available on toxicity.
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
The reactivity of catechol sulfate (CS) with hydroxide ion is
may also be sulfonated by SO3 and various of its complexes.16
anomalous relative to other sulfuric acid diesters. Surprising is the
However, the yields are generally low and the desired products
very high rate of cleavage1 and that only S O fission is observed.2
difficult to obtain in pure form. Exemplary of CS sulfonation is
X-ray crystal data suggest this unusual reactivity to be due to ring-
the preparation of substituted methionic acid 5 (eq 3).15
strain effects and a distorted nonplanar conformation.3
RCOOK
HO
n-BuLi , CS
Conversion of Amines to Sulfamate Salts. Amines may
DMF
O
O O
be cleanly converted to catecholyl esters of sulfamic acids on
SO2 S 25 °C, 24 h
SO2 THF,  78 °C
40% O2
49%
reaction with CS.4 These readily isolable esters may be effi-
ciently hydrolyzed on mild alkaline treatment. This two-step pro-
KOH
HO
cess affords greater selectivity than possible with other reagents
H2O
(3)
such as ClSO3H and SO3 complexes,5 fuming H2SO4,6,7 and RCOO
O
RCOO
S
100 °C, 8 h
KO3S
SO3K
KO3S
SO2Cl2/SbCl5.8 As example of the selectivity observed with CS,
O2
60%
(5)
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 Me3N/SO3 gives 3 directly, it is formed as a minor com- O-²-D-Glu-2-O-²-D-Glu
ponent (15 20%) of a complex mixture. Ester 2 is then cleanly
converted to 3 by reaction with alkali.
R =
H
KOH
CS
O
H
Et3N, DMF
SO2 H2O
(1)
R-NH2 RNHSO3K
0 °C, 1 h NHR 100 °C, 1 h
OH
100% 89%
Related Reagents. Chlorosulfonic Acid; Sulfur Trioxide;
(3)
(1)(2)
Sulfuryl Chloride.
OMe
O OH
1. Kaiser, E. T.; Katz, I. R.; Wulfers, T. F., J. Am. Chem. Soc. 1965, 87,
OH
R =
3781.
2. Kaiser, E. T.; Zaborsky, O. R., J. Am. Chem. Soc. 1968, 90, 4626.
OH O
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.
The CS sulfamation procedure is limited to primary aliphatic
5. Gilbert, E. E. Sulfonation and Related Reactions; Interscience: New
amines. Aromatic amines react only slowly with CS and secondary York, 1965; Chapter 7.
amine/CS condensation products are not cleaved by alkali. 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. 14. Lee, C.-H.; Lee, M. S.; Lee, Y.-H.; Chung, B. Y., Bull. Korean Chem.
Soc. 1992, 13, 357.
8. Weiss, G.; Schulze, G., Justus Liebigs Ann. Chem. LA 1969, 729, 40.
15. DuBois, G. E.; Stephenson, R. A., J. Med. Chem. 1985, 28, 93.
9. DuBois, G. E., J. Org. Chem. 1980, 45, 5373.
16. Gilbert, E. E. Sulfonation and Related Reactions, Interscience: New
10. Dorlars, A., Methoden Org. Chem. (Honben-Weyl) 1958, XI/2, p 711.
York, 1965; p 33.
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. Grant E. DuBois
13. Gilbert, E. E. Sulfonation and Related Reactions, Interscience: New The Coca-Cola Company, Atlanta, GA, USA
York, 1965; Chapter 7.
A list of General Abbreviations appears on the front Endpapers