Sulfonyl chlorides reaction with ammonia

The reaction gives a mixture of the ortho- 53 and para- 54 products. The ortho -compound is converted into saccharine by reaction with ammonia and oxidation and the para-compound toluene-p-sulfonyl chloride 54, or tosyl chloride, is sold as a reagent for converting alcohols into leaving groups. 

Sulfonamides can in general be obtained very smoothly by treating sulfonyl chlorides with ammonia694 or dry, powdered ammonium carbonate.217,695 The reaction with ammonia is carried out in aqueous solution or better in an inert organic solvent in the cold it is advisable to use an excess of ammonia so as to avoid hydrolysis to the ammonium sulfonate or formation of the disulfonylamide, (RSC NH. 

Marshall et al (4) reported a method of synthesis of acetohexamide which Involves the reaction of the diazonlum salt from p-ami noacetophenone with sulfur dioxide to afford the sulfonyl chloride which Is then converted to the sulfonamide by reaction with ammonia. Elaboration via the carbeunate with cyclohexylamine affords acetohexamide. Another reported method (16) uses p-chloroacetophenone as the starting material. Both methods are outlined In Scheme 2. 

What acids might be present in the crude sulfonyl chloride that would cause an exothermic reaction with ammonia ... 

Based on the results of this experiment, which is more nucleophilic hydroxide ion (HO ) or ammonia (NH3) Explain. 7-59. Outline a suitable mechanism to account for the conversion of the sulfonyl chloride group to the sulfonamide group by reaction with ammonia. 

Chloro-3-(dunethylamino)-2,4-(l/f,3//)-quinazolinedione 50 by heating with excess chlorosulfonic acid at 100 °C afforded the 6-sulfonyl chloride 51, which on subsequent reaction with ammonia gave the sulfonamide 52 (Equation 12). Some of the substituted derivatives of type 52 showed diuretic properties. ... 

An iV-acylamino acid (1) is reacted with thionyl chloride yielding the oxazolone (2), which by treatment with an aroyl chloride gave (3). The latter compound was hydrolysed and decarboxylated to yield (4), which reacted with chlorosulfonic acid-thionyl chloride to give the sulfonyl chloride, and subsequent reaction with ammonia afforded the sulfonamide (5) (Scheme 1). 

N -Heterocyclic Sulfanilamides. The parent sulfanilamide is manufactured by the reaction of A/-acetylsulfanilyl chloride with excess concentrated aqueous ammonia, and hydrolysis of the product. Most heterocycHc amines are less reactive, and the condensation with the sulfonyl chloride is usually done in anhydrous media in the presence of an acid-binding agent. Use of anhydrous conditions avoids hydrolytic destmction of the sulfonyl chloride. The solvent and acid-binding functions are commonly filled by pyridine, or by mixtures of pyridine and acetone. Tertiary amines, such as triethylamine, may be substituted for pyridine. The majority of A/ -heterocycHc sulfanilamides are made by simple condensation with A/-acetylsulfanilyl chloride and hydrolysis. 

Thiophenethiols are prepared by reduction of the sulfonyl chlorides or, more conveniently, by the reaction of Grignard rea-gents or thienyllithium compounds with sulfur. They have also been obtained by cleavage or thienyl alkyl sulfides with sodium in liquid ammonia. 3-Thiophenethiol is a by-product in the commercial thiophene synthesis. Thiophenethiols have recently also been prepared by a synthesis involving Friedel-Crafts reaction of 2,4-dinitrobenzenesulfenyl chloride with thiophenes, followed by basic cleavage of the resulting sulfide. ... 

Then, as described in U.S. Patent 2,55416, the 2-acetylamido-5-mercapto-1,3,4-thiadiazole is converted to the sulfonyl chloride by passing chlorine gas into a cooled (5°-10°C) solution in 33% acetic acid (66 parts to 4 parts of mercapto compound) used as a reaction medium. Chlorine treatment is continued for two hours. The crude product can be dried and purified by recrystallization from ethylene chloride. The pure compound is a white crystalline solid, MP l94°C,with decomposition, when heated rapidly. The crude damp sulfonyl chloride is converted to the sulfonamide by addition to a large excess of liquid ammonia. The product is purified by recrystallization from water. The pure compound is a white, crystalline solid, MP 259°C, with decomposition. The yield of sulfonamide was 85% of theory based on mercapto compound. 

The treatment of sulfonyl chlorides with ammonia or amines is the usual way of preparing sulfonamides. Primary amines give N-alkyl sulfonamides, and secondary amines give N,N-dialkyl sulfonamides. The reaction is the basis of the Hinsberg test for distinguishing between primary, secondary, and tertiary amines. N-Alkyl sulfonamides, having an acidic hydrogen, are soluble in alkali, while N,N-dialkyl sulfon-... 

Reactions with sulfonyl chloride in the presence of ammonia yield sulfonic acid hydrazides ... 

As expected, the reaction of a sulfonyl chloride with ammonia produces a sulfonamide. This reaction is used in the preparation of sulfanilamide, a sulfa drug that was one of the first antibacterial agents ... 

Sulfinic acids and sulfoxides are not particularly common, being readily oxidized to the sulfonic acids and sulfones, respectively. Sulfonic acids have high melting points and probably exist as zwitterions. They are amphoteric, but mainly display the characteristics of weak acids. The sulfonic acid group activates an adjacent halogen to nucleophilic displacement, and may itself be displaced, e.g. reaction of alkylamines with benzimidazole-2-sulfonic acid. Imidazolesulfonic acids resist esterification and acid chloride formation, and are only hydrolyzed by concentrated hydrochloric acid at 170 °C the 2-isomers are more resistant than the 4- or 5-isomers. Aqueous alkali converts the free acids into hydroxy derivatives. Sulfonyl chlorides are accessible via the thiols (Section 4.07.3.6.1) which react with ammonia to form sulfonamides, or are reduced by tin(II) chloride to thiols (77JHC889). 

Sulfonyl chlorides as well as esters and amides of sulfonic acids can be hydrolyzed to the corresponding acids. Sulfonyl chlorides can by hydrolyzed with water or with an alcohol in the absence of acid or base. Basic catalysis is also used, though of course the salt is the product obtained. Esters are readily hydrolyzed, many with water or dilute alkali. This is the same reaction as 10-4, and usually involves R —O cleavage, except when R is aryl. However, in some cases retention of configuration has been shown at alkyl R, indicating S—O cleavage in these cases. Sulfonamides are generally not hydrolyzed by alkaline treatment, not even with hot concentrated alkali. Acids, however, do hydrolyze sulfonamides, but less readily than they do sulfonyl halides or sulfonic esters. Of course, ammonia or the amine appears as the salt. However, sulfonamides can be hydrolyzed with base if the solvent is HMPA. ... 

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