Sulfamide1

(R = H)

[7803-58-9]  · H4N2O2S  · Sulfamide  · (MW 96.13) (R = Et)

[6104-21-8]  · C4H12N2O2S  · N,N-Diethylsulfamide  · (MW 152.25) (R = n-Pr)

[19757-10-9]  · C6H16N2O2S  · N,N-Dipropylsulfamide  · (MW 180.31) (R = t-Bu)

[13952-67-5]  · C8H20N2O2S  · N,N-Di-t-butylsulfamide  · (MW 208.37) (R = NO2C6H4)

[19757-13-2]  · C12H10N4O6S  · N,N-Bis(4-nitrophenyl)sulfamide  · (MW 338.33)

(useful for synthesis of substituted 1,2,6-thiadiazine 1,1-dioxides,3 1,2,5-thiadiazolidine 1,1-dioxides,7 sulfamoylamidines,11 and nitriles12)

Physical Data: R = H, mp 93 °C, dipole moment 3.9 D; R = Et, mp 67 °C; R = n-Pr, mp 118 °C; R = t-Bu, mp 140 °C; R = NO2C6H4, mp 197 °C.

Solubility: R = H, freely sol water, hot alcohol, acetone; more acidic than urea, and can act as a dibasic acid.

Preparative Methods: N,N-diethylsulfamide is prepared by addition of a solution of Sulfuryl Chloride (0.889 mol) in petroleum ether, at -30 °C, to a mixture of ethylamine (2.2 mol) and Pyridine (1.76 mol) in petroleum ether. Stirring at rt followed by acidic workup affords N,N-diethylsulfamide (45% yield). Large alkyl (C3 to C6) sulfamides are prepared by addition of a solution of an alkylamine (2.5 mol) in chloroform to a mixture of pyridine (4 mol) and sulfuryl chloride (1 mol) in chloroform at -5 °C. Similar workup as above gives N,N-dialkylsulfamides in 58-69% yield.1,2

Handling, Storage, and Precautions: use in a fume hood.

General Discussion.

Sulfamide reacts with 1,3-diketones (eq 1)3 and b-amino a,b-unsaturated ketones (eq 2)4 to provide substituted 2H-1,2,6-thiadiazine 1,1-dioxides. The reaction of sulfamide with Malononitrile (eq 3)5 or cyanogen (eq 4)6 under acid catalysis yields 3,5-diamino-4H-1,2,6-thiadiazine 1,1-dioxides or 3,4-diamino-1,2,5-thiadiazole 1,1-dioxide. 3-Imino-4-substituted 1,2,5-thiadiazolidines7 can be prepared from sulfamide, aldehydes, and metal cyanides (eq 5).

N,N-Cyclic sulfamides are synthesized by heating sulfamide with 1,2- or 1,3-diamines in pyridine or diglyme solvent (eqs 6 and 7).8,9 Reaction temperature is an important factor in this cyclization, because at lower temperature uncyclized products may be obtained (eq 6).8

Sulfamide can be used to form eight-membered heterocyclic compounds10 and the very toxic tetramethylenedisulfotetramine (eqs 8 and 9).11

N-Sulfamoylamidines,12 nitriles,13 and azoalkanes2 have been prepared by using sulfamide or substituted sulfamides (eqs 10-12).

Related Reagents.

Sulfuryl Chloride; N,N-Sulfuryldiimidazole.


1. Hantzsch, A.; Holl, A. CB 1901, 34, 3420.
2. Ohme, R.; Preuschhof, H; Heyne, H-U. OSC 1988, 6, 78.
3. Elguero, J.; Goya, P.; Martinez, A. H 1989, 29, 245.
4. Alberola, A.; Andres, J. M.; Gonzalez, A.; Pedrosa, R.; Vicente, M. S 1991, 355.
5. Alkorta, I.; Aran, V. J.; Bielsa, A. G.; Stud, M. JCS(P1) 1988, 1271.
6. Aran, V.; Ruiz, J. R.; Davila, E.; Alkorta, I.; Stud, M. LA 1988, 337.
7. Lee, C.-H.; Korp, J. D.; Kohn, H. JOC 1989, 54, 3077.
8. Takai, H.; Obase, H.; Nakamizo, N.; Teranishi, M.; Kubo, K.; Shuto, K.; Hashimoto, T. CPB 1985, 33, 1104.
9. Mignani, S.; Gueremy, C.; Malleron, J.-L.; Truchon, A.; Peyronel, J.-F.; Bastart, J.-P. H 1992, 34, 907.
10. Lee, C.-H.; Kohn, H. H 1988, 27, 2581.
11. Lee, C.-H.; Kohn, H. JOC 1990, 55, 6098.
12. Yanagisawa, I.; Hirata, Y.; Ishii, Y. JMC 1987, 30, 1787.
13. Kvita, V.; Sauter, H. HCA 1990, 73, 883.

Seung Hoon Cheon

Sandoz Research Institute, East Hanover, NJ, USA



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