Diazotation sulfonamides

Of these dyes, Acid Yellow 151 (37) still has the greatest market among the yellows. As reported by USITC, production had increased to 1989 tons in 1985 from 706 tons in 1975. It is produced by coupling diazotized 2-amino-l-phenol-4-sulfonamide to acetoacetanilide followed by metallizing with cobalt to obtain a 1 2 cobalt complex. Acid Orange 24 (38), which is sulfanilic acid coupled to resorcinol to which diazotized mixed xyUdines have been coupled, is an unsymmetrical primary diasazo dye with a bihinctional coupling component. 

Amino groups bound to sulfur can be replaced by fluorine via diazotization. In contrast to carboxylic acid amides, fluorodediazoniation of aromatic sulfonamides IS readily accomplished to give sulfonyl fluorides in high yields [52, 7S (equation 16) Tetrazotization-fluorination of sulfanilamide can also be effected to give a 38% yield of p-fluorobenzenesulfonyl fluoride [52],... 

Diazotization of the primary amine [3, 17] followed by coupling with a-naphthol or N-(l-naphthyl)-ethylenediamine. Sulfonamides also react [18]. 

Amino-l,5-diphenyltriazole is deaminated by diazotization in ethanolic solution and warming. 1-Aminotriazoles are deaminated in high yield by treatment with nitrous acid. Removal of a toluene-p-sulfonamido group can be accomplished in two steps by acid hydrolysis followed by diazotization, or in one step by treatment of the 1-toluene-p-sulfonamide derivative with sodium in liquid ammonia. ... 

Chlorobenzenesulfonamide can be prepared from -chloroaniline by diazotization and treatment of the resulting diazonium salt with sulfur dioxide and hydrochloric acid in the presence of cuprous or cupric chloride to yield the sulfonyl chloride (Ref. 4) which is converted to the sulfonamide with ammonia. 

Co111 exhibits a greater tendency to form complexes with nitrogen-donor ligands than with oxygen-donor ligands. Thus the azo dye from diazotized 2-amino-1 -hydroxybenzene-5-sulfonamide and acetonylbenzthiazole affords the 1 2 cobalt... 

Reaction of chlorosulfonic acid with mono- [141] or disazo dyes [142] yields sulfonyl chlorides, which can then be transformed into cationically substituted sulfonamides by reaction with dialkylaminoalkylamines. The coupling product of diazotized 2-anisidine with 2-hydroxynaphthoic acid arylide upon such treatment dyes paper red, and the azo dye from tetrazotized dianisidine and l-phenyl-3-methyl-5 -pyrazolone gives yellowish orange shades. 

In the synthesis of the unsymmetrical 1 2 cobalt complex 18 [68928-31-4] [30], the 1 1 cobalt complex 17 and the azo dye made by coupling of 1-acetoacetyl-amino-2-ethylhexane with diazotized 2-aminophenol-4-sulfonamide are intro-... 

The simplest 1,3-dipolar cycloadditions of diazomethane were presented in Figure 12.33. Diazomethane is generated from sulfonamides or alkyl carbamates of A-nitrosomethylamine. The preparation shown in Figure 12.37 is based on the commercially available para-toluenesulfonylmethylnitrosamide (Diazald). In a basic medium, this amide forms a sulfonylated diazotate A by way of a [1,3]-shift, which then undergoes a base-mediated 1,3-elimination (cf. Section 4.1.1). 

Sulfonamides in pharmaceutical formulations have been determined by diazotization and coupling with m-aminophenol, a-naphthylamine and N- 1-naphthylethylenediamine dihydrochloride in sulfuric acid-trichloroacetic acid, and measuring the absorbance at 435, 520 and 545 nm, respectively. Absorbance is linear in the concentration... 

A colorimetric method for microdetermination of sulfonamides based on diazotization of the drug with sodium nitrite and hydrochloric acid has been reported (59). The diazonium salt is then coupled with 8-hydroxyquinoline in alkaline medium and the absorbance of the developed color measured at its maximum wavelength. A similar method involves diazotization and coupling of the sulfonamide with indole in alkaline solution to form an intense yellow azo dye which exhibits maximum absorption at 449 nm. Beer s law is obeyed over the concentration range 1-32 /ig/ml with a relative standard deviation of less than 2% (60). The reaction of sulfonamides with chloramine-T in sulfuric acid gives a yellow product which is suitable for the determination of sulfonamides in different formulations. It has an accuracy similar to that of the Bratton and Marshall method (61). 

Sianesi and co-workers39,40 utilized o-aminophenylacetonitrile (48) as starting material for a four-step synthesis of compounds related to 47. Thus, diazotization of aniline 48 and treatment of the diazonium salt with S02/Cu2Cl2 yielded the sulfonyl chloride 49 (Eq. 11). Treatment of 49 with primary amines produced the corresponding sulfonamides 50 which were cyclized by sulfuric acid to the 3-imino compounds 51. Finally, aqueous hydrolysis of the imine 51 produced the desired 1,2-benzothiazin-3 (2H)-one 1,1-dioxides (47) (R = H, Et, and Ph) (Eq. 11). 

The amino group is readily diazotized in aqueous solution, and this reaction forms a basis for the assay of sulfas. Aldehydes also react to form anils, and the yellow product formed with 4-(dimethylamino)benzaldehyde can be used for detection in thin-layer and paper chromatography. Chromatographic retention values have been determined in a number of thin layer systems, and have been used as an expression of the lipophilic character of sulfonamides (23). These values have corresponded well with Hansch lipophilic parameters determined in an isobutji alcohol—water system. 

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. 

El-Alfy, E. Mahmoud, F. Ibrahim, A. M. R. Hebeish, A. Synthesis and applications of new azo dyes. Part IV. Dye preparation by coupling of V-(m-hydroxyphenyl)-p-toluene sulfonamide with diazotized... 

A similar strategy which provides additional functionality already built into the pyrazole nucleus, results from condensation of a hydrazine imine 62 with ethyl(ethoxymethylene)cyanoacetate. Conversion of the amine to the sulfonamide 64 is accomplished by a similar diazotization. 

The polyvinylamine prepared by the Dynapol group has been functionalized with p-acetamidobenzene sulfonyl chloride and the sulfonamide adduct has been diazotized after deacetylation. 

A further example of pyrazolone dye is Acid Red 38. This dye is the chromium complex of the azo compound made by coupling diazotized 2-amino-5-nitrophenol with meta-(3-methyl-5-oxo-2-pyrazolin-l-yl)-benzene-sulfonamide. It is used as a dye for wool and nylon. Acid Red 38 has one advantage over dyes such as Mordant Black 17 in that the dyer does not have to form the chromium complex by a separate operation during the dyeing process. 

Scheme 13.9 Diazotization of aryl amines to access sulfonamides.

In summary, sulfonamides are most commonly prepared by the reaction of amines with sulfonyl halides. Aryl sulfonyl chlorides may be accessed from C-H bonds by chlorosulfonylation, from C-S bonds by oxidation, from C-N bonds by diazotization, or from C-X bonds by metalation. Approaches to all l sulfonamides are more limited as they are typically prepared by either oxidative chlorination of thiols or addition of organometallic nucleophiles to sulfur electrophiles. Traditional sulfonamide preparation has frequently necessitated harsh reagents and conditions, but the development of Pd-catalysed approaches and discovery of new sulfur dioxide sources allow for operationally simple sulfonamide synthesis under mild conditions. Future directions in sulfonamide synthesis will likely involve the direct C-H installation of sulfonamides without the use of hazardous reagents. 

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