Sulfathiazole sulfa drugs

Fig.4.24. Separation of 12 sulfa drugs (see text for details). Peaks 1 = phthalyl sulfathiazole 2 = sulfaquinoxaline 3 = sulfabenzamide 4 = sulfisoxazole S = sulfachlorpyridazine 6 = sulfadimethoxine ...

Suggest a synthesis of sulfathiazole. a sulfa drug, from the indicated starting material ... 

Most of the sulfa drugs possess the general structure (17), and many of the most useful compounds contain a heterocyclic nucleus. Important examples include sulfapyridine (18), sulfadiazine (19), sulfathiazole (20) and sulfamethoxazole (21) (Figure 3). Sulfapyridine... 

Over the years, however, the sulfa drugs used in medicine have not remained static, as one might have predicted in the early forties. Three of the most widely used sulfa drugs today have been developed rather recently sulfi-soxazole, sulfadimethoxine, and sulfamethoxypyridazine. Sulfanilamide, itself, sulfathiazole, and sulfapyridine have been displaced largely by these drugs in human therapy. This illustrates drug obsolescence. 

In the early twentieth century, one of the first commercial synthetic drugs containing thiazole was sulfathiazole, a short-acting sulfa drug. ... 

In addition to the substances described, several other compounds have been described as lipase inhibitors. Thus pancreatic lipase is inhibited by thiourea, chloroethanol, formaldehyde (351), by quinine and atoxyl (352), by chaulmoogric acid (353), by cinnamate and ricinoleate (354), by several fatty acids (355), by vitamin C (356), by chlortetracycline (357), by isoamyl alcohol, isoamyl isobutyrate, and other esters (358), and by several sulfa drugs, such as sulfadiazine or sulfathiazole (340, 359, 360). Pancreatic lipase is unaffected by diisopropyl fluorophosphate (DFP) but is inhibited by diethyl-p-nitro-phenyl phosphate (349, 361). Milk lipase, however, is stated to be inhibited by DFP (362). 

A spectrophotometric method for some sulfa drugs starts with the formation of an orange yellow colored azo product by the diazotization of sulfonamides and is followed by a coupling reaction with 3-aminophenol in aqueous medium. The absorbance of the resulting orange yellow azo product is measured at 460 nm and the product is stable for 6 days at 27°C. The method is successfully used for the determination in various pharmaceutical preparations of the sulfonamides dapsone, sulfathiazole, sulfadiazine. 

Another method for the determination of sulfa drugs is based on the formation of a violet-colored azo product by the diazotization of sulfonamides, followed by a coupling reaction with iminodibenzyl in alcohol medium. Absorbance of the resulting violet azo product is measured at 570-580 nm and is stable for 24 h at 27°C. Beer s law is obeyed in the concentration range of 0.05-6.0 ppm at the wavelength of maximum absorption. The method is successfully employed for the determination of sulfathiazole, sulfadiazine, sulfacetamide, sulfamethoxazole, sulfamerazine, sulfaguanidine, and sulfadimidine. The proposed reaction mechanism for the formation of the violet azo dye is shown in Figure 3. 

Outline a synthesis for the sulfa drug, sulfathiazole, starting from benzene. The primary aminothiazole ring system is available ... 

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