Sulphonamides acetyl derivatives

Sulphonamides upon heating with acetyl chloride are converted into the A -acetyl derivatives or sulphonacetamides ... 

Disposition in the Body. Sulfametopyrazine is a long-acting sulphonamide and is readily absorbed after oral administration. It is acetylated in the body, 5 to 10% of the sulfametopyrazine in the blood being in the form of the A -acetyl derivative which is inactive. It is slowly excreted in the urine, about 70% of the excreted material being the acetyl derivative and about 14 to 20% being unchanged drug. 

A further type of conjugation reactions concerns the reactions serving to remove aromatic amines and sulphonamides as well as aromatic amino acids bound to acetic acids. The products obtained are named acetyl derivatives and they are catalysed by acetyl transferases. The process is referred to as acetylation and the amino group of a given chemical substance always reacts with acetic acid. 

The acetyl derivative of a primary sulphonamide is addic and its neutralization equivalent may be determined by titration of an alcoholic solution of the derivative with standard sodium hydroxide using phenolphthalein as indicator. 

Acetyl derivative. When treated as described above for simple sulphonamides, sulphonamides of the type R.SO2NHR yield acetyl derivatives which differ from those of simple sulphonamides in that they are not acidic hence, determination of a neutralization equivalent (see 1(6) on page ISO) is not applicable. 

The most cautionary examples of selective metabolisms are those in which man behaves differently from most other mammals, for herein lies one of the dangers in transferring results from laboratory animals to man. Here are some examples. The only animals that dehydrogenate quinic acid to benzoic acid are man and the Old World primates, for not even the New World primates do so. The antibacterial sulphonamide sulpha-dimethoxine is excreted by man and the primates as the N -glucuronide, whereas the common laboratory animals excrete it as the AT-acetyl-derivative (Adamson, Bridges and Williams, 1966). Other aromatic amines such as aniline and sulphanilamide are acetylated in man, and many other mammals, as well as in most species of birds, amphibia, reptiles, and fish nevertheless dogs, frogs and turtles do not perform acetylation. Further examples of different metabolic paths followed by man on the one hand and mammals on the other have been traced for amphetamine, phenylacetic acid, and 6-propylthiopurine in Section 3.4 (p. 82). 

The procedure is not usually applicable to aminosulphonic acids owing to the interaction between the amino group and the phosphorus pentachloride. If, however, the chlorosulphonic acid is prepared by diazotisation and treatment with a solution of cuprous chloride in hydrochloric acid, the crystalline chloro-sulphonamide and chlorosulphonanilide may be obtained in the usual way. With some compounds, the amino group may be protected by acetylation. Sul-phonic acids derived from a phenol or naphthol cannot be converted into the sulphonyl chlorides by the phosphorus pentachloride method. 

Chlorosulphonation of 4 -chloro-o-acetotoluidine yields the eorresponding sulphonyl chloride derivative whieh on amination forms the sulphonamide derivative. Oxidation of the methyl moiety gives the respeetive anthranilamide derivative whieh on hydrolysis eliminates the acetyl group to yield the substituted anthranilic acid. Fusion of this amino acid with propionamide first gives rise to an intermediate by the loss of a mole of water and ultimately helps in the closure of the ring to generate the quinazoline ring system. Catalytic reduction of this finally produces the official compound. 

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