DE1193062B - Process for the preparation of 1-amino-3-trifluoromethylbenzene-4, 6-disulfamide - Google Patents

Description

FEDERAL REPUBLIC OF GERMANY

GERMAN

PATENT OFFICE

EDITORIAL

int. U .:

German class: 12 q- 6/03

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1193 062
O 6967IV b / 12 q
November 24, 1958
May 20, 1965

The invention relates to a method of manufacture of l-amino-S-trifluoromethylbenzene ^ o-disulfamide. This connection has not yet been described in the literature. The disulfamide which can be produced according to the invention is a physiologically active compound that can be used as a diuretic.

The process according to the invention for the preparation of l-amino-3-trifluoromethylbenzene-4,6-disulfamide is characterized in that l-amino-3-trifluoromethylbenzene with at least 2 equivalents of chlorosulfonic acid in the presence of an alkali chloride, such as Sodium chloride, and is preferably reacted at an elevated temperature. The obtained 1-amino-3-trifluoromethylbenzene-4,6-disulfonyl chloride is then converted into the corresponding disulfamide with aqueous ammonia by methods known per se. The ammonia is preferably used in an aqueous solution.

It is already known to prepare arylsulfonic acid chlorides from the corresponding sulfonic acids analogously to the preparation of the acid chlorides of carboxylic acids. Further procedures are being implemented of the sodium salts of arylsulfonic acids at high temperature with phosphorus pentachloride or phosphorus oxychloride. Another method for the preparation of aryl sulfonic acid chlorides, e.g. B. Benzenesulfonic acid chloride, consists in the reaction of at least 2 equivalents of chlorosulfonic acid with benzene. if the chlorosulfonic acid is not used in considerable excess, is formed as a by-product in significant amount of diphenyl sulfone. If the reaction with one equivalent of chlorosulfonic acid in an organic solvent, such as carbon tetrachloride, is carried out, the free Sulfonic acid. It is also already known to use m-chloroaniline at 150 ° C in the presence of sodium chloride to convert with chlorosulfonic acid into the l-amino-3-chloro-4,6-disulfonyl chloride. By treating the The sulfonamides are obtained from sulfonic acid chlorides with aqueous or concentrated ammonia.

The sulfonation of benzene and its derivatives with chlorosulfonic acid is just like nitration, Halogenation and Friedel-Crafts reaction called electrophilic aromatic substitution. at monosubstituted benzene derivatives, the place of entry of a second substituent is determined by the resonance and determines the field effect or inductive effect that the first substituent exerts on the benzene nucleus. A distinction is made between ortho-para-directing and meta-directing substituents. In the aniline is that Amino group per se is a strongly ortho-para-directing substituent. In acidic medium, e.g. B. at the Process for the preparation of 1-amino-3-trifluoromethylbenzene-4,6-disulfamide

Applicant:

Olin Mathieson Chemical Corporation,
New York, NY (V. St. A.)

Representative:

Dipl.-Chem. Dr. rer. nat. V. Vossius,
Patent attorney, Munich 27, Pienzenauer Str. 92

Named as inventor:

Harry L. YaIe,

Jack Bernstein, New Brunswick, N.J. (V. St. A.)

Claimed priority:
V. St. v. America November 25, 1957
(698 377)

By nitration or sulfonation, however, it is converted into an ammonium group, which has a strong meta-directing effect. The chlorine atom in chlorobenzene is also an ortho-para directing substituent. In trifluoromethylbenzene, on the other hand, the trifluoromethyl group directs the second substitution into the meta position. The trifluoromethyl group lowers the electron density of the benzene nucleus both by resonance and by induction (field effect). The nitration of trifluoromethylbenzene according to Fred. S warts, Chemisches Zentralblatt, 92, III, p. 32 (1921), in 99% yield m-Nitrotrifmormethylbenzol and only traces of the other two isomers. F. S warts' findings were confirmed by Eugen Wertyporoch, Liebigs Annalen der Chemie, Vol. 493, pp. 153-165. In the bromination of trifluoromethylbenzene with iron as a catalyst according to JH S im ο η s and EO R am 1 er, J. Americ. Chem. Soc, 65, pp 389-392 (1943), is obtained in the 52 ° / ₀ yield m-Bromtrifluormethylbenzol, traces of the 3,4-dibromo compound and unreacted starting compound.

The place of entry of a third and optionally fourth substituent in disubstituted benzene derivatives generally depends on the substituent whose influence is greatest. In agreement

509 570/413

Claims (1)

3 4 One gets mood with the theory z. B. heated from the steam bath. After cooling, m-chloroaniline is, as already discussed above, the l-amino-3-trifluoromethylbenzenesulphonic acid which has crystallized out with chlorine and l-ammo-3-cMor-4 ₃ 6- & sulphonyl chloride. 4,6-disulfamide filtered off. The compound melts Both the chlorine atom and the amino group after recrystallization from water at 236 to 238 ° C. Benzene nucleus are ortho-para-directing substituents. 5 Yield about 8 g. Mp. Pure 246 to 247 ° C.
In the sulfonation of m-trifluoromethylaniline with. . _T
Chlorosulfonic acid should be expected that as a result of the B e ι s ρ ι el 2
strongly negative resonance and field effect of the tri- (a) A mixture of 208 g of m-trifluoromethylaniline fluoromethyl group and the conversion of the amino and 1600 ml of tetrachloroethane is stirred in the strongly acidic reaction medium in the amino at a temperature below 50 ° C with 165 g of chloromonium group, the meta-substitution of sulfonic acid has now been added. Then the mixture of 84 g is preferred in terms of speed. However, this is sodium chloride added and 1 hour to 144 to surprisingly not the case, because after the 146 ⁰ C heated. The mixture is heated to 25 to 35 ⁰ C but inventive method is obtained in good cooled. By distilling off the tetrachloroethane yield of the l-amino-3-trifluoromethylbenzene-4,6-di-15 and unconverted chlorosulfonic acid under verminsulfonyl chloride, that is, the entry of the third and that pressure can result in the 4-trinuomethylvated substituents in the benzene nucleus in 2- aminobenzenesulfonic acid can be isolated.
ortho-para position to the amino group as to the tri- (b) The solution of (a) is then at a tempefluoromethyl group. It is also surprising that 90 ml of tetrachloroethane dilute the reactive fluorine atoms of trifluoromethyl 20 with 90 ml of tetrachloroethane, cooled and, with stirring, 1766 g of chlorine group under the vigorous and strongly acidic reactsulfonic acid and 853 g of sodium chloride are added. Dation conditions are not split off hydrolytically, the mixture is heated for 1 hour to 80 to 90 ° C (cf. JH Simons and EO Ramler, and then for 3 hours to 140 to 146 ° C J. Americ. Chem. Soc, 65, p . 389 to 392 [1943]). heated. After cooling down, the reaction The examples explain the mixture according to the invention slowly stirred into ice and water. travel. After 30 minutes the lower layer is separated, Example 1 which the resulting l-amino-3-trifluoromethyl- contains benzene-4,6-disulfonyl chloride. (G 176, 1.5 moles) to 100 ml of 99 ⁰ / "strength chlorosulfonic (c) The lower layer of (b) is carried out at 0 to 10 ° C acid are slowly added dropwise 20 g of 30 to 11 concentrated aqueous ammonia solution at room temperature (0.125MoI) 1-amino-3-trifluoromethylbenzene added. (28% NH ₃ ) stirred in; then the mixture This mixture is then heated to 80 to 90 ° C. for 1 hour with stirring, cooled and with gradually a total of 90 g (1.5 mol) of sodium 3200 ml of concentrated aqueous ammonia solution chloride entered within an hour. That relieves. Two layers are formed. The lower one The viscous reaction mixture that has stood is then separated into a 35 layer and applied to tetrachloroethane. an oil bath heated to 180 ° C and worked for 2 hours. kept this temperature. During this time the upper aqueous layer will be treated with excess the reaction mixture solidifies, and the stirring is heated to hydrochloric acid. It crystallizes on cooling ends. The reaction mixture is then dissolved in a 1-amino-3-trifluoromethylbenzene-4,6-disulfamide Ice bath cooled and after cooling quickly with 40 and is filtered off and dried. Yield 267 g, Dilute 500 ml of ice water and stir until a fine m.p. 240 to 242 ° C. yellow crystal suspension has formed. The crystals _n , are filtered off, dried and dissolved in 600 ml of ether. stirred in. The yellow ether solution is given by a process for the production of l-amino-3-tri- if any insoluble matter is present, decanted with 45 fluoromethylbenzene-4,6-disulfamide, thereby Washed with water, dried over magnesium sulfate, characterized in that l-amino-3-tri- and concentrated on the steam bath to about 50 ml. fluoromethylbenzene with at least 2 equivalents The ether solution contains the l-amino-3-trifluoromethyl chlorosulfonic acid in the presence of an alkali benzene-4,6-disulfonyl chloride, which reacts as crystalline sub-chloride and the resulting l-amino-3-tri- punch can be separated. 50 fluoromethylbenzene-4,6-disulfonyl chloride with aqueous For conversion into the corresponding 4,6-disulfonous ammonia in a manner known per se into the amide, the ethereal solution is cooled in an ice bath and transferred to the corresponding disulfamide. and slowly with 50 ml of concentrated aqueous Ammonia added. A violent reaction sets in. Considered publications: Finally, the reaction mixture is 55 journ for 1 hour. At the. Chem. Soc, 79 (1957), pp. 2028-2029. When the registration was announced, a test report (one page) was displayed. 509 570/413 5.65 © Bundesdruckerei Berlin