| dc.description.abstract | The present thesis consists of three parts, all of them dealing generally with synthetic drugs consisting of N?-substituted sulphanilamide derivatives of S-alkyl-isothioureas and S-alkyl-isothiosemicarbazides.
Part I
This part deals with the synthesis of N?-substituted sulphanilamide derivatives derived from S-alkyl-isothioureas only. Nine such alkyl-isothioureas, viz. ethyl, propyl, butyl, allyl, isoamyl, benzyl, p-nitrobenzyl, p-methoxybenzyl, and ethylene bis, have been prepared specially for this work and condensed with p-acetaminobenzenesulphochloride to form the corresponding acet-sulphanilyl derivatives. The acet-compounds were further hydrolysed by suitable methods to the free bases, and these have been isolated and characterised.
It is interesting to note that an attempt to condense S-acetylisothiourea with p-acetaminobenzenesulphochloride did not prove successful as the acetyl derivative was too weakly basic to react. The new isothioureas made in the course of this work are butyl and p-methoxybenzyl derivatives, and they have been characterised by their picrates. The acetyl sulphanilyl derivatives are all new compounds, as also the free bases obtained from them by acid hydrolysis, except the free base of the S-ethylisothiourea derivative, a paper on which by Roblin (J. Amer. Chem. Soc., 1942, 64, 1682) and Mayer (Rev. Med. France, Nov.–Dec. 1941, 3–19) appeared and were available to the author only after this work was completed.
The structure of these sulphanilyl-isothioureas has been concluded to be of the following type:
H?N–C?H?–SO?–N:C(S-alkyl)–NH? (VIII),
in preference to the alternative formula:
H?N–C?H?–SO?–NH–C(S-alkyl)=NH (IX).
Part II
This part of the thesis deals with N?-substituted sulphanilamide derivatives derived from N-aryl-S-alkyl-isothioureas. Such disubstituted (N and S) isothioureas that have been prepared for these condensations are six N-phenyl-S-alkyl-isothioureas, the alkyl radicals being ethyl, propyl, butyl, allyl, benzyl, p-nitrobenzyl, respectively, and three other N-aryl-S-ethyl-isothioureas, the other aryl radicals being p-tolyl, p-anisyl, and p-naphthyl, respectively. Each of these has been condensed with p-acetaminobenzenesulphochloride to form the N?-acet-sulphanilyl di-substituted (N and S) isothiourea derivatives. The free bases corresponding to these have been obtained by hydrolysis with 10% aqueous hydrochloric acid.
Of the nine isothioureas enumerated above, excepting the S-ethyl-, S-propyl-, and S-benzyl-N-phenylisothioureas, all the remaining six have been synthesised for the first time and have been characterised by their picrates. All the acet-condensation products have been synthesised for the first time, and so also the free bases derived from them by hydrolysis with dilute hydrochloric acid.
The general structure of these compounds has been concluded to be of the following type:
H?N–C?H?–SO?–N:C(S-alkyl)–NH–aryl,
in preference to the alternative formula:
H?N–C?H?–SO?–NH–C(S-alkyl)=N–aryl.
Part III
This part of the thesis deals firstly with N?-substituted acet-sulphanilamide derivatives derived from six S-alkyl-1-phenyl-isothiosemicarbazides, the alkyl radicals being ethyl, propyl, butyl, allyl, benzyl, and p-nitrobenzyl. All these isothiosemicarbazides are quite new and have been prepared for the first time; and these have been characterised by their picrates.
Secondly, acet-sulphanilamide derivatives of two S-alkyl-acetone-thiosemicarbazones, the alkyls being ethyl and propyl, and of S-ethyl-benzaldehyde-thiosemicarbazone have been synthesised for the first time.
The general structure of all these condensation products has been proved to be of the following type, illustrated in the case of the 1-phenyl derivative:
AcHN–C?H?–SO?–N:C(S-alkyl)–NH–NH–C?H? (IV),
in preference to the alternative formulae:
HN=C(S-alkyl)–N(SO?–C?H?–NHAc)–NH–C?H? (III) and
AcHN–C?H?–SO?–NH–C(S-alkyl)=N–NH–C?H? (?).
This was established by a careful analysis of the main product of the acid hydrolysis of one of these compounds, viz. acet-sulphanilyl-S-ethyl-1-phenyl-isothiosemicarbazide, and proving its non-identity with a specially prepared specimen of the N?-sulphanilyl phenylhydrazide. This phenyl hydrazide was specially prepared for the purpose by treating pure phenyl hydrazine with p-acetaminobenzenesulphochloride and hydrolysing the resultant acetyl compound with alcoholic hydrochloric acid. Further confirmation was obtained by identifying sulphanilamide as the main product of the hydrolysis of the above compound, viz. acet-sulphanilyl-S-ethyl-1-phenyl-isothiosemicarbazide. | |
