Disulfonyl chloride

Until the mid-1960s, phenylenediamines were used primarily for oxidative purposes the para isomer was of major importance. Since then, the use of phenylenediamines to manufacture polymers has far exceeded their use for oxidative purposes. The y -phenylenediamines, (2,4 and 2,6)-toluenediamine, are widely used for the manufacture of polyurethanes. Phenylenediamines are dihinctional and react with other dihinctional compounds, such as dianhydrides, diacyl chlorides, dicarboxyHc acids, and disulfonyl chlorides to give polyamides. Phenylenediamines also give polymers with epoxides, diols, diacetals. 

The sulfonation of 2-acetamidomcthylthiophene and of 2-acetami-dothiophene attracted considerable interest in connection with work on potential thiophene chemotherapeutics, although from this point of view these investigations have given little reward. Sulfonation of 2-acetamidomethylthiophene with chlorosulfonic acid occurs in the 5-position. At room temperature 100% sulfuric acid yields 80% 5-acetamido-2-thiophcnesulfonic acid. With chlorosulfonic acid sulfonation cannot be stopped at the monosubstitution stage and 2-acetamido-3,5-thiophene disulfonyl chloride is obtained. - In recent Russian work the isolation of a monosulfonated product is claimed, however. With the activating -f-M-substituents, disubstitution, which is easily achieved, always leads exclusively to 3,5-disub-... 

Aj Preparation of 5-Trifluoromethylaniline-2,4-Disulfonylchloride— H ml of chlorosulfonic acid Is cooled in an ice bath, and to the acid is added dropwise while stirring 26.6 grams of a,a,a-trifluoro-m-toluidine. 105 grams of sodium chloride is added during 1-2 hours, whereafter the temperature of the reaction mixture is raised slowly to 150°-160°C which temperature is maintained for three hours. After cooling the mixture, ice-cooled water is added, whereby 5-trifluoromethylaniline-2,4-disulfonyl chloride separates out from the mixture. 

B) Preparation of S-Trifluoromethyl-2,4-Disulfamylaniline—The 5-trifluoromethylaniline-2,4-disulfonyl chloride obtained in step (A) is taken up in ether and the ether solution dried with magnesium sulfate. The ether is removed from the solution by distillation, the residue is cooled to 0°C, and 60 ml of ice-cooled, concentrated ammonia water is added while stirring. The solution is then heated for one hour on a steam bath and evaporated... 

After removal of ether on the steam bath, the residual 5-chloroaniline-2,4-disulfonyl chloride, which may be crystallized from benzene-hexane MP 130° to 132°C, was cooled in an ice bath and treated with 150 ml of 2B% ammonium hydroxide in a 2-liter Erlenmeyer flask. The mixture was heated on the steam bath for 1 hour, cooled and the product collected on the filter, washed with water and dried. Upon crystallization from dilute alcohol 5-chloro-2,4-disulfamylaniline was obtained as colorless needles, MP 251° to 252°C. 

A product consisting largely of 5-chloro-4-hydroxybenzene-1,3-disulfonyl chloride separates as a gum which solidifies on standing for about 1 hour. The solid product is collected on a Buchner funnel, washed with water and thoroughly dried in air at room temperature. 

A mixture of this crude product (approximately 302 grams, 0.92 mol) and 480 grams (2.3 mols) of phosphorus pentachloride is heated for 1 hour at 120°-140°C in a 2 liter round-bottomed flask. The resulting clear solution is poured on ice. 4,5-Dichlorobenzene-1,3-disulfonyl chloride separates immediately as a solid. It is collected by filtration and washed with water. While still moist, it is added in portions during about 20 minutes to 1 liter of concentrated ammonia water contained in a 3 liter beaker surrounded by a cold water bath. The reaction mixture is then allowed to stand for 1 hour without cooling after which it is heated on a steam bath for about 30 minutes while air is bubbled through it, in order to remove some of the excess ammonia. It is then filtered, acidified with concentrated hydrochloric acid and chilled. 

Chilled 3-trifluoromethylaniline (32.2 g) is added dropwise over a 45-minute period to 150 ml of chlorosulfonic acid with stirring and cooling. The ice bath is removed and 140 g of sodium chloride is added over 3 hours. The mixture is heated on a water bath for 30 minutes, then gradually up to 160°C over 6 hours. The cooled reaction mixture is diluted with 500 ml of an ice water slurry and taken into ether. The ether is dried and evaporated to leave 5-triflu oromethylamine-2A-disulfonyl chloride. 

B) Preparation of 4-Amino-2-Chloro-5-(Methylsulfamyl)Benzenesulfonamide The 5-sub-stituted-2,4-dlsulfamyl anilines may be prepared by procedures described in the literature, for example, the general procedures in Monatsch. Chem. vol. 48, p 87 (1927), which involves the treatment of a m-substituted aniline with from 10 to 20 parts by weight of chlorosulfonic acid followed by the gradual addition of from about 90 to 170 parts by weight of sodium chloride. The resultant mixture is heated at approximately 150°C for about 2 hours after which the reaction mixture is poured into water and the resultant 5-substituted aniline-2,4-disulfonyl chloride is filtered and is then treated with concentrated ammonium hydroxide or suitable amine by standard procedures to obtain the corresponding disulfonamide. 

The 3,7-disulfonyl chloride of dibenzothiophene 5,5-dioxide has been isolated from the reaction of biphenyl with chlorosulfonic acid. The reaction proceeds via the 2,4,4 -trisulfonyl chloride of biphenyl. This reaction has now been extended to give sulfonic acid derivatives of 3-phenyl- and 3-biphenylyldibenzothiophene 5,5-dioxide. Treatment of p-terphenyl with oleum or chlorosulfonic acid at 100° yields (141a) (46%), and similarly p-quaterphenyl yields 141b (47%). A later... 

More reliable reagents for the preparation of sulfinic acids are zinc [694, 695], sodium sulfide [249] and sodium sulfite [2S2. These reagents not only stop the reduction at the stage of the sulfinic acids (in the form of their salts) but do not reduce other functions present in the molecules. In the reduction of anthraquinone-l,5-disulfonyl chloride with sodium sulfide below 40° anthraquinone-l,5-disulfinic acid was obtained in 83.5% yield [249], and p-cyanobenzenesulfonyl chloride was reduced to p-cyanobenzenesulfinic acid in 87.4% yield [252]. 

After sufficient chloroform has been evaporated to give a solution volume approximating 250 ml., the solution is cooled in an ice bath and the crystalline product collected on a filter. By further concentration of the mother liquor, an additional quantity of naphthalene-1,5-disulfonyl chloride is obtained. A total yield of 85-115 g. (65-88%) of recrystallized material results m.p. 181-183°. 

Naphthalene-1,5-disulfonyl chloride has been prepared by the reaction of naphthalene with chlorosulfonic acid.2 3 5 However, the yields are generally poor and the conditions difficult to reproduce. 

Synthetically useful routes to dibenzo[c,e J[l,2]dithiins are normally based on cyclizations of biphenyI-2,2 -disulfonyl chlorides. A method applied successfully to the parent compound reduces the precursor with zinc in acetic acid to generate the bis thiol, which is then gently oxidized to the dithiin using iron(II) chloride (66HC(21-2)952). An alternative one-step reductive cyclization, which has been applied to the preparation of the 2,9- and 3,8-dinitro derivatives, involves reduction of the appropriate bis sulfonyl chlorides with hydriodic acid in acetic acid (68MI22600). Yet another reductive cyclization uses sodium sulfite followed by acidification, and these conditions lead to dibenzo[c,e][1,2]dithiin 5,5-dioxide. The first step of the reaction is reduction to the disodium salt of biphenyl-2,2 -disulfinic acid which, on acidification, forms the anhydride, i.e. dibenzo[c,e][l,2]dithiin 5,5,6-trioxide. This is not isolated, but is reduced by the medium to the 5,5-dioxide (77JOC3265). Derivatives of dibenzo[c,e] [1,2]dithiin in oxidation states other than those mentioned here are obtainable by appropriate oxidation or reduction reactions (see Section 2.26.3.1.4). 

Very recently it has been reported that the Friedel-Crafts condensation of aromatic disulfonyl chlorides with aromatic ethers has been successfully effected to yield high molecular weight polymers (20)... 

Aldehydes are still used to prepare diuretics (82USP4338435) and antihypertensives (87USP4634689), e.g., when 106 is heated with 6-bromohexanal, thiadiazine 107 (X = Br) results. Substituted sulfonamide 106 can apparently be made from the corresponding disulfonyl chloride by sequential amidation with methylamine and then benzylamine. The presence of the bromine moiety in 107 allows 107 [X = PO-(OH)CH2COOH] to be made by reaction with diethyl carboethoxy-methylphosphonite [(EtO)2PCH2COOEt] and subsequent saponification of the phosphinate and acetate groups. Hence, condensation in trifluo-... 

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