ON THE COMPLEXATION OF SULFAMIDE DERIVATIVES WITH QUINONE

B. V. TRONOV, N. D. STRELNIKOVA, L. T. SHCHEGLOVA

In the study of the chemical properties of organic compounds, in particular in elucidating the regularities of the mutual influence of atoms in molecules, attention is now being directed toward determining the type of reactivity of substances. For this purpose it is most convenient to use reactions that proceed without deep restructuring of the molecule. Reactions of complex formation meet this requirement [1]. It is best to take complex-forming reagents with a strong predominance of some one type of activity—electron-donor or electron-acceptor. Among organic compounds, amines are strong electron donors, while simple ethers are weaker ones. Electron-acceptor reagents include acids and polynitro compounds of the benzene series, for example, m-dinitrobenzene and, to an even greater degree, 1,3,5-trinitrobenzene. Quinones are also known as strong complex-forming agents, convenient also in that their complex-formation processes are accompanied by a sharp change in color. However, up to now there has been no firmly established opinion on the type of reactivity of quinones. Some authors believe that, in complexes of the quinhydrone group, quinone plays the role of an electron donor, while phenol or hydroquinone act as electron acceptors, forming a hydrogen bond. The opinion is also expressed that quinhydrone and similar complexes have an ionic structure [2].

In one of the earlier works of Tomsk organic chemists it was noted that in certain complex-formation reactions, namely in interaction with carbonyl compounds and with alkali salts [3], quinone behaves like aromatic polynitro compounds, displaying even greater activity than dinitrobenzene. This indicates the predominance of electron-acceptor properties. Comparison of the activity of phenols with respect to quinone leads to the same conclusion [4]. Phenol or hydroquinone, having relatively weak acidic properties, form stable complexes with quinone. The quinone complexes of trichlorophenol and tribromophenol, where the activity of the hydroxyl hydrogen is increased, could be obtained only by a topochemical method [5], and these products readily lose quinone in air. Still more acidic phenols and dinitrophenols, as well as benzoic acid, do not add to p-benzoquinone at all. Picric acid again reacts.

The facts listed can be explained only by the fact that quinone exhibits predominantly electron-acceptor properties. It probably reacts at the carbonyl carbons, which have a rather large effective positive charge [6], owing to which the unshared electron pairs of phenolic oxygens can be attracted. In complex formation with very strong acids, to which picric acid belongs, quinone, one must suppose, reacts as an electron donor.

The understanding of the structure of most complexes of the quinhydrone type set forth here is also supported by the sharp deepening of the color in comparison with the components of these complexes. An analogous change in color also occurs upon complex formation of nitro compounds in those cases when the latter function as electron acceptors, for example with amines.

All that has been said compels us to classify quinones as reagents with rather strong electron-acceptor activity. As such a reagent, quinone can be used in determining the type of reactivity of other organic compounds.

In the present work we used p-benzoquinone in studying the complex formation of medicinal substances of the sulfamide group. Twelve sulfamide preparations were taken; their mixtures with quinone were studied colorimetrically. Ethyl alcohol and dioxane served as solvents. It was observed that the solvents themselves react with quinone on prolonged standing. In alcohol a noticeable change in color begins after 2 hours, in dioxane after 8 hours. Therefore we had to carry out measurements with freshly prepared solutions; the delay was no more than 1 hour. A serious inconvenience was the poor solubility of the preparations, which forced us to use solutions with concentrations not exceeding 1/4000, and sometimes 1/16000 mole. For comparison, experiments were performed with well-studied systems: aniline–nitrobenzene (weak interaction) and benzidine–m-dinitrobenzene (considerably stronger interaction). In the first system, for example, the formation of a complex becomes noticeable already at a concentration of 1/400 mole. Thus, under our conditions the presence of a positive result in the quinone–sulfamide preparation systems at concentrations of 1/16000 and even 1/32000 mole already indicates considerable activity of the components with respect to one another.

According to the results of our measurements, the greatest reactivity in interaction with quinone was shown by sulfanilacetamide (albucid), which gave a sharp maximum of optical density at a molecular composition of 1 M of sulfamide to 2 molecules of quinone, moreover in both solvents and at a concentration of 1/16000 mole. Sulfanilaminopyridine (sulfidine) reacted noticeably only in dioxane; 2-sulfanilamino-5-ethyl-3,4-thiodiazole (globucid) gave a positive result only in ethanol, as did sulfanyl-cyanamide; the latter, however, is almost insoluble in dioxane.

The simplest of the sulfanilamide preparations—white streptocide, 2-sulfanilaminothiazole (norsulfazole), 2-sulfanilaminomethyl-4-thiazole (sulfazole), 2-sulfanilamino-4,6-dimethylpyrimidine (sulfodimezine), sulfanilguanidine (sulgin), sulfanilurea (urosulfan), 2-phthalyl-sulfanilaminothiazole (phthalazole), 4-sulfanil-sulfanilamide (disulfan)—gave negative or excessively indistinct results.

The mechanism of formation of complexes with quinone, apparently, may be different for different sulfamide preparations. Thus, for sulfidine the attachment of quinone molecules to the nitrogen atoms of the amino group and of the pyridine ring is most probable; but of the two nitrogens of albucid, only that in the amino group can be expected to have electron-donor activity sufficient for complex formation. The amino group is situated between sulfur and a carbonyl and should have acidic properties, all the more since here transfer of hydrogen to one of the oxygen atoms is more probable. It is not excluded that one molecule of quinone attaches to the amino group according to the electron-acceptor type, and the second through formation of a hydrogen bond, i.e., as an electron donor. Sulfamide has a very

active cyano group. Two molecules of this substance can attach to different atoms of quinone—one to carbon, the other to oxygen—and it is possible for both to attach to the oxygen atoms. Sulfimide has such strong acidic properties that it reacts even with bicarbonates of alkali metals.

Experimental Part

For the work, sulfamide preparations recrystallized from ethyl alcohol were used. The purity of the substances taken was checked by melting point. Quinone was purified by sublimation; the purified quinone had m.p. 115.2°.

For the colorimetric study, solutions were prepared in 96% ethyl alcohol, methyl alcohol, and dioxane. Measurements were carried out more often at intervals of 10 mole percent, and in the more interesting regions of the diagrams at intervals of 5 and 2.5 mole percent. The total concentrations of the components were different; they depended on the solubility of the substances taken for study—from 1/200 to 1/3200 mole.

The experiments were conducted at a temperature of 20–21°. The optical density of the solutions was measured with an FEK-M photoelectric colorimeter in a 50 ml cuvette with a blue light filter. Each system was colorimetered three times. The measurement results are presented in Figs. 1 and 2.

Fig. 1. Optical density of the sulfamide–quinone system.
I. Albucid–quinone in dioxane, 1/600 M. II. Albucid–quinone in ethanol, 1/600 M. III. Albucid–quinone in dioxane, 1/600 M.

Fig. 2. Optical density of the sulfamide–quinone system.
I. Globucid–quinone in ethanol, 1/400 M. II. Globucid–quinone in dioxane, 1/400 M.
III. Sulcidimid–quinone in ethanol, 1/400 M.

Conclusions

1. The work provides a justification for the use of quinone as a sufficiently active complexing agent with predominantly electron-acceptor reactivity.

2. Twelve systems were studied colorimetrically, consisting of quinone and medicinal preparations of the sulfanilamide group. Chemical interaction was found in four systems.

3. Considerations are presented concerning the structure of the complexes found.

References

1. Tronov B. V. and Strelnikova N. D. Izvestiya TPI, 71, p. 63, Tomsk, 1952.

2. Gragerov I. P. and Mikhailukhin G. P. KhFKh, 24, p. 582, 1950.

3. Tronov B. V., Dyakonova-Shubina L. P. and Zvonova E. A. ZhRKhO, 59, p. 333, 1927.

4. Sokolovich V. B. Izvestiya TPI, 77, p. 164, Tomsk, 1953.

5. Tronov B. V. and Sokolovich V. B. Izvestiya TPI, 83, p. 91, Tomsk, 1956.

6. The State of the Theory of Chemical Structure in Organic Chemistry. Report of the Commission of the Division of Chemical Sciences of the Academy of Sciences of the USSR, 1954.

Corrections and Notes