Sulfanilamide production

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. 

It is often advantageous to proceed to a desired product through two nucleophilic displacements rather than directly when one can exploit a difference in the reactivity of two leaving groups. An example is the conversion of 4-chloro-2,6-dimethoxypyrimidine (109) (not satisfactorily reactive with sulfanilamide anion) by means of trimethylamine into the more reactive trimethylammonio derivative 110. Conversion of chloro-quinohnes and -pyrimi-dines into nitriles is best accomplished by conversion (with sulfite) into the sulfonic acids before reaction with cyanide. 

Our results on the reaction of 2,4-dichloropyrimidine with another anion should be pointed out in connection with the fallacy of considering sole product (isolated) to mean absolute selectivity. From the reaction of 2,4-dichloropyrimidine with sulfanilamide anion in molten acetamide (65°, 1 hr), the major product, 2-chloro-4-sulfanilamidopyrimidine, is isolated in good yield paper chromato-... 

A sulfanilamide drug of prolonged action, 2-p-aminobenzenesulfamido-4-methylpyiimidine (sulfomerazine 162), first prepared by Japanese chemists from acetacetic aldehyde in 82% yield (49JPJ447), ranks among practically valuable 2-amino-4-methylpyrimidine derivatives. Later, a synthesis of this product directly from l-methoxybut-l-en-3-yne (100°C, AcONa, AcOH, 3 h) in 64% yield has been developed (76MI1). 

Similar selectivity in displacement reactions is shown by 3,6-dichloropyridazine (153) (available by halogenation of the product from maleic anhydride and hydrazine). Thus, reaction of the dihalide with the sodium salt from sulfanilamide (93) affords fiulfachloropyridazine (104). Reaction of this last with sodium methoxide under somewhat more drastic conditions results in displacement of the remaining chlorine to give sulfamethoxypyrida-zine (105). ... 

Systematic modification of the sulfanilamide molecule in order to maximize the hypoglycemic activity led to the observation that the sulfonamide is best replaced by a sulfonylurea function. Modification on both the aromatic ring and the substituent on the terminal nitrogen modulates the activity of the products. ... 

Possibly the most significant discovery in the metabolism of aromatic azo compounds had implications that heralded the age of modem chemotherapy. It was shown that the bactericidal effect of the azo dye Prontosil in vivo was in fact due to the action of its transformation product, sulfanilamide, which is an antagonist of 4-aminobenzoate that is required for the synthesis of the vitamin folic acid. Indeed, this reduction is the typical reaction involved in the first stage of the biodegradation of aromatic azo compounds. 

Solution of sulfanilamide is more readily obtained in this way than by treating the amide at once with 6 N acid for, in the latter case, the salt precipitates at first and redissolves only slowly. If acid stronger than 6 N is used, a larger volume is required to dissolve the sulfanilamide hydrochloride, and the product is partly held in solution as dichlorosulfanilamidc hydrochloride unless the solution is diluted. If 4 A acid is used, the reaction is much slower without any worthwhile decrease in the color of the product. 

Dibromoaniline has been prepared many times 3"5 6 n by bromination of sulfanilic acid and desulfonation of the product or its salts. Fuchs12 brominated sulfanilamide with free bromine and desulfonamidated it in the usual manner. Reduction of the corresponding nitro compound13 and other methods 14 also have been employed. 

CASRN 3337-71-1 molecular formula C8H10N2O4S FW 230.24 Soil Asulum is not persistent in soils because its half-life is approximately 6-14 d (Hartley and Kidd, 1987). The short persistence time is affected by soil temperature and moisture content. The half-life of asulam in a heavy clay soil having a moisture content of 34% and maintained at 20 °C was 7 d (Smith and Walker, 1977). In soil, sulfanilamide was reported as a product of hydrolysis. In nonsterile soils, this compound degraded to unidentifiable products (Smith, 1988) which may include substituted anilines (Bartha, 1971). 

The performance of the activated sludge process for the treatment of wastewater from a synthetic drug factory, has been reported [14,15,45]. One of the biggest plants of its kind in Asia, M/S Indian Drugs and Pharmaceutical Ltd., Hyderabad, went into production in 1966 to make sulfa drugs such as sulfanilamides antipyretics (phenacetin), B-group vitamins, antimbercular drugs (isonicotinic acid hydrazide) and antihelminthics, and so on. 

Sulfisoxazole Sulfisoxazole, ATi-(3,4-dimethyl-5-isoxazolyl)sulfanilamide (33.1.19), is synthesized by reacting 4-acetylaminobenzenesulfonyl chloride with 5-amino-3, 4-dimethylisoxazol (33.1.17), which is in turn synthesized by heterocyclization of 2-methy-lacetylacetonitrile with hydroxylamine, and subsequent acidic hydrolysis (hydrochloric add) of the protective acetyl group in the resulting product (33.1.18) [18,19]. 

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