Articles written in Proceedings – Section A
Volume 11 Issue 4 April 1940 pp 298-311
The synthesis and the chemotherapeutic effects in experimental
The realtionship of chemical constitution to chemotherapeutic action in this group of compounds has been outlined basing on a study of the therapeutic properties of about 500 compounds till now reported. While the substitution at the amino radical of sulphanilamide does not produce compounds of increased activity but only suppress the polyvalent action of the original compound, the substitution at the amide part of the molecule, especially by a heterocyclic ring, produces compounds of increased activity, particularly in infections in which sulphanilamide is very little effective. The highly active diaminodiphenylsulphone derivatives have to be properly modified to be used in practical therapy. There does appear to be a sort of specificity of the compounds towards different types of infections so that the new compounds produced should be tested in different types of infections also.
Volume 12 Issue 3 September 1940 pp 274-283
The synthesis of thirteen (N4) amino-substituted sulphanilamide compounds of thiozal and related derivatives is described. None of them showed any activity in experimental
Volume 13 Issue 5 May 1941 pp 386-389
In an attempt to assess the antibacterial effect of sulphanilamides with various heterocyclic rings introduced into the (N1)-sulphonamide radical, typical derivatives, of guanidine, thiodiazole, uracil, barbituric and pyrimidine have been synthesised and are reported here.
Volume 14 Issue 6 December 1941 pp 1- Erratum
Volume 14 Issue 6 December 1941 pp 630-635
In the course of the attempts to study the effects of the different types of substituents in the molecule of 2-N1-sulphanilamidothiazole, the synthesis of a series of 2-N1-sulphanilamido-5-alkyl- and 2-N1-sulphanilamido-4-methyl-5-alkyl- thiazoles, wherein the alkyl group varies from ethyl to hexyl, have been effected and these compounds are described.
Volume 15 Issue 6 June 1942 pp 432-436
With the object of studying the antibacterial effect of sulphanilamide derivatives with cyclic substituents at the sulphonamide radical, typical N1-sulphanilamido derivatives of diphenylether, phenanthrene, chrysene, dibenzofuran, carbazole, coumarin, acridine, tetrahydroquinoline and phenanthridine have been synthesised and are reported. Aminosulphonamide derivatives of naphthalene and diphenyl are also described.
Volume 16 Issue 2 August 1942 pp 115-125
Sulphanilylguanidine condensed with ethyl acetoacetate and its α-alkyl derivatives to yield 2-sulphanilamido-4-methylpyrimidone and 2-sulphanilamido-4-methyl-5-alkylpyrimidones respectively. Experiments have been recorded which support these structures and a number of intermediate compounds are described. Ethyl formylacetate condensed with sulphanilyl-guanidine to furnish 2-sulphanilamidopyrimidone. Hydroxymethyleneacetone and hydroxymethylene ethylbutylketone failed to condense with sulphanilylguanidine to yield the corresponding pyrimidines in appreciable yields. Mesityl oxide, on the other hand, has yielded two products which are represented provisionally as the two possible pyrimidine derivatives (XIV) and (XV).
Volume 16 Issue 2 August 1942 pp 126-128
A number of carboxylic acid derivatives of 2-sulphanilamidothiazole with the acid grouping attached directly or through alkyl radicals to the thiazole ring at the positions 4 or 5, are described.
Volume 18 Issue 6 December 1943 pp 355-359
The synthesis of various derivatives of sulphathiazole with alkyl and substituted alkyl substituents at the ring nitrogen of the thiazole nucleus has been described. Of these compounds only the methyl derivative showed good therapeutic activity in experimental streptococcal, pneumococal and plague infections in mice.
Volume 18 Issue 6 December 1943 pp 360-363
2-Aminothiazole condensed with acetsulphanilylchloride in aqueous solution or suspension in the presence of sodium bicarbonate, calcium carbonate or barium carbonate to yield 2-diacetsulphanilylamidothiazole m.p. 128–29°; the same product is also obtained by condensing 2-aminothiazole with two molecular equivalents of acetsulphanilylchloride in pyridine or by condensing 2-acetsulphanilamidothiazole with acetsulphanilylchloride in alkaline solution. This compound on boiling with alcohol isomerises into 2-acetsulphanilimido-3-sulphanilylthiazolone. These two products are hydrolysed by acid or alkali to sulphathiazole in good yield. A process of preparation of sulphathiazole is described.
Volume 21 Issue 1 January 1945 pp 34-40
Starting from 4-nitro-4′-aminodiphenylsulphone, by diazotisation and further transformation, the corresponding 4′-chloro, bromo, iodo and hydroxy compounds were obtained. For the preparation of the chloro and bromo compounds it was found to be advantageous to treat the diazonium salt with an aqueous solution of copper sulphate and sodium halide. Treatment of the diazo product with cuprous oxide or copper bronze in alcohol yielded 4-nitrodiphenylsulphone. The 4′-cyano-compound could not be prepared smoothly by the Sandmeyer’s reaction but only by fusing the 4′-halo derivative with cuprous cyanide. All the nitro-compounds were smoothly reduced to the amino derivatives by means of iron dust in acidified alcohol or-sodium hydrosulphite. Compounds of formula (III) to (VIII) have been prepared by treating 4-nitro-4′-aminodiphenylsulphone and 4-nitro-4′-aminodiphenylsulphide each with α-picoline, 2∶4-dimethylthiazole and 2-hydroxy-4-methylthiazole respectively in the presence of paraformaldehyde.
Volume 22 Issue 6 December 1945 pp 343-358
Volume 22 Issue 6 December 1945 pp 359-361
That chloracetonitrile condenses with thiourea to yield 2∶4-diaminothiazole hydrochloride has been confirmed. The diacetamino compound prepared from this by acetylation has been found to be identical with that prepared from ethyl 2-aminothiazole-4-carboxylate by the Curtius method. Chloracetonitrile reacted with other thioamide compounds but the products are found to be not 4-aminothiazole derivatives.
Ethyl 2-methylthiazole-4-carboxylate could not be converted into 2-methyl-acetaminothiazole.
Volume 22 Issue 6 December 1945 pp 362-378
Three methods of synthesising thiazole derivatives unsubstituted in position 2 of the thiazole ring have been investigated to ascertain their scope. The reactions involving the condensation of thioformamide with α-halogenoketones are best effected by treating the halogenoketones with a mixture of formamide and phosphorous pentasulphide; syntheses of 4-methylthiazole, 4∶5-dimethylthiazole, 4-methyl-5-acetylthiazole and ethyl 4-methylthiazole-5-carboxylate are described as examples. By this method thiazole and ethyl thiazole-4-carboxylate could not be prepared.
2-Aminothiazole, the 5-methyl and 5-ethyl derivatives have been converted into the corresponding 2-chloro and 2-bromo derivatives in good yields by diazotising the aminothiazoles in a mixture of phosphoric acid and nitric acid or about 45 per cent. sulphuric acid and treating the diazonium products with an aqueous solution of copper sulphate and sodium halide. Treatment of the diazonium solutions with cuprous oxide in alcohol or calcium hypophosphite yielded the deaminated products, the latter giving better yields than the former reagent. These reactions are not of universal applicability and their scope has been ascertained by studying them in a number of cases. 2-Chloro-5-nitrothiazole and 2-bromo-5-nitrothiazole have been prepared by diazotising 2-amino-5-nitrothiazole in dilute sulphuric acid containing copper-sulphate and the sodium halide.
The preparation of 2-hydroxythiazole derivatives by condensing α-halogenoketone with either the thiocyanates or ammonium thiocarbamate has been studied using chloracetone, dichloracetone, α-chloromethyl-ethylketone, chloracetylacetone and ethyl α-chloroacetoacetate. In the case of the chloroderivatives of β-ketonic ester and β-diketone, ammonium thiocarbamate yields the expected 2-hydroxy thiazole derivative while the product obtained using the thiocyanates is of doubtful constitution. The 2-hydroxythiazol compounds could be converted into the 2-chlorothiazole in good yields by treating with phosphorous oxychloride. Saturation of α-thiocyanomethylethylketone with hydrogen chloride furnished 2-chloro-4∶5-dimethylthiazole.
Volume 28 Issue 6 December 1948 pp 556-562
Condensation of 2-bromo-5-nitrothiazole with sulphanilamide yielded (i) in the presence of potassium carbonate and copper powder, 2-sulphaniamido-5-nitrothiazole and (ii) in alcoholic solution the isomeric N4-(5-nitro-2-thiazolyl)-sulphanilamide. 2-Hydroxy-4-methyl-5-aminothiazole and 2∶4-dimethyl-5-aminothiazole condensed with acetsulphanilylchloride to yield respectively 2-hydroxy-4-methyl-5-acetsulphanilamidothiazole and 2∶4-dimethyl-5-acetsulphanilamidothiazole. The latter, on hydrolysis, furnished 2∶4-dimethyl-5-sulphanilamidothiazole, which was about as active as sulphathiazole in experimental pneumococcal and
Volume 28 Issue 6 December 1948 pp 563-573
In the course of attempts to prepare quinoline derivatives with substituted diguanide side chains, the methods of syntheses of N1-
Volume 31 Issue 1 January 1950 pp 21-25
Twenty-three compounds have been synthesised as possible lipophilic chemotherapeuticals of the sulphonamide and sulphone series. Among such compounds are the hydnocarpic acid derivatives of N4-
Volume 33 Issue 6 June 1951 pp 364-367
To trace the antimalarial activity in the thiazole compounds, twenty-one thiazole derivatives of general formula I have been synthesised by the standard method of reacting the corresponding thiourea derivatives with chloracetal, chloracetone and ethyl
Volume 34 Issue 1 July 1951 pp 17-19
Nineteen diarylsulphones of general formulæ (I) and (II) listed in the table have been synthesised by the Hinsberg reaction, with a view to study them for their action against gram positive anaerobes.
Volume 34 Issue 1 July 1951 pp 43-48
Of the methods available for the synthesis of the 4-aminoquinoline derivatives, the best one was found to consist of passing ammonia into a mixture of 4-chloroquinolines and phenol maintained at 130 60. Accordingly 4-amino-7-chloroquinoline, 4-amino-6-methoxyquinaldine, 4-amino-8-methoxy quinaldine, and 4-amino-6-chloroquinaldine were prepared in good yields. Attempts to prepare the guanidine and biguanide derivatives of formula (I) and (II) failed. The amino group in position 4 of the quinolines showed properties of neither the aliphatic nor the aromatic amino group.
4-Chloroquinolines do not react with guanidine salts to yield the 4-guanidinoquinolines. Similarly 4-methoxyquinolines also do not react with guanidine salts.
Volume 34 Issue 1 July 1951 pp 54-60
Attempts made to evolve a general method for the synthesis of 4-(guanidylphenylamino) quinoline derivatives of formula (II) are described. By reacting 4-chloro-6-methoxyquinaldine, 4-chloro-8-methoxyquinaldine, 4:6-dichloroquinaldine and 4:7-dichloroquinoline individually with
The reaction of 4-(
Volume 34 Issue 3 September 1951 pp 178-182
Ten thiazolylaminoquinolines of formula (I) have been prepared by heating the 4-chloroquinolines with 2-aminothiazoles in phenol medium, at about 150–60°. In some cases, instead of the compounds of formula (I), only the 4-phenoxyquinolines could be isolated. The 2-chlorolepidines do not undergo this condensation at all. 4:7-Dichloroquinoline condensed with 2-amino-4-methylpyrimidine to yield the compound (II); but 2-aminopyrimidine and 2-amino-4-methyl-6-chloropyrimidine did not react with the chloroquinoline. Evidence has been presented to show that in the condensation of the chloroquinolines with amines in phenol medium, the phenoxyquinoline is not the intermediate as was supposed by some authors. A different mechanism seems to operate.
Volume 34 Issue 3 September 1951 pp 183-186
Twenty-one aryquinolylsulphones described in the table have been prepared by reacting the chloroquinolines with substituted arylsulphinic acids. The 4-chloroquinolines furnish the sulphones very readily and these sulphones are easily hydrolysed to the corresponding 4-hydroxyquinolines.
These compounds do not show any activity when tested for their prophylactic activity in mosquitoes against
Volume 37 Issue 5 May 1953 pp 643-651
Phenylenediguanidine derivatives of formula (I) have been synthesised to assess their antimalarial activity. The method consists in condensing phenylthiourea derivatives of formula (VI) with a series of isothiocyanates, to obtain the dithiourea derivatives (VII), the di-S-methyl derivatives of which reacted with ammonia to furnish the diguanidine derivatives (I). The other methods tried to prepare diguanidine derivatives are also described. Eleven
Volume 37 Issue 5 May 1953 pp 652-659
Twenty-two pteridines of formula (I) and twenty-one thiopteridines of formula (II) have been synthesised
Volume 37 Issue 6 June 1953 pp 758-764
In connection with the study of the orienting influences in the thiazole nucleus, 2-methylthiazole, 4-methylthiazole, 5-methylthiazole, 2-hydroxythiazole, 2-methoxythiazole, 5-acetamidothiazole and 5-acetamidothiazole-2-carboxylic acid have been nitrated and brominated and the results obtained have been presented. The significance of the results is discussed in the next part.
Volume 38 Issue 1 July 1953 pp 45-57
Volume 38 Issue 1 July 1953 pp 58-63
Chrysean has been isolated in two forms; whether they are stereosoimers or only dimorphic forms is discussed. A mechanism of formation of chrysean is suggested. With methyl iodide it gives readily the S-methyl derivative which reacts easily with aniline,