Synthesis of dihydrates of biphenyl-2,2'-diglyoxal and 4-iodobiphenyl-2,2'-diglyoxal
Abstract Generated abstract
This paper reports the preparation of two previously undescribed glyoxal derivatives, biphenyl-2,2′-diglyoxal dihydrate and 4-iodobiphenyl-2,2′-diglyoxal dihydrate, as compounds intended for subsequent study of physiological properties. The noniodinated compound was synthesized by selenium dioxide oxidation of biphenyl-2,2′-diacetyl, while the iodinated analogue was obtained from 2-iodophenanthrenequinone through Grignard addition, oxidation to the diacetyl intermediate, and selenium dioxide oxidation followed by hydration. The authors provide experimental conditions, purification procedures, yields, melting points, and elemental analyses, supporting the identification of the isolated dihydrates.
Full Text
SYNTHESIS OF DIPHENYL-2,2′-DIGLYOXAL AND 4-IODODIPHENYL-2,2′-DIGLYOXAL DIHYDRATES
A. N. NOVIKOV, A. P. BELYAEVA
(Presented by the scientific seminar of the departments and laboratories of organic synthesis)
In recent years, with the aim of searching for antiviral compounds, numerous derivatives of glyoxal have been synthesized [1, 2, 3, 4, 5]. Some representatives of this series of substances have been recommended for use in the treatment of viral diseases, including influenza [6, 7].
To clarify the dependence of physiological action on the structure and composition of the substance, we have obtained diphenyl-2,2′-diglyoxal and 4-iododiphenyl-2,2′-diglyoxal, which have not been described in the literature.
Experimental Part
Synthesis of diphenyl-2,2′-diglyoxal dihydrate
\[ \text{[[chemical structure: biphenyl with adjacent } \mathrm{H_2O\cdot OHCOC} \text{ and } \mathrm{COCHO\cdot H_2O} \text{ substituents]]} \]
Diphenyl-2,2′-diacetyl, obtained from phenanthrenequinone by the known method [8], was oxidized with selenium dioxide to diphenyl-2,2′-diglyoxal. To a mixture of 6.5 g of selenium dioxide, 50 ml of dioxane, and 2 ml of water at a temperature of 70°C, 6.7 g of diacetyldiphenyl in 30 ml of dioxane was added dropwise. The mixture was then boiled for 5 hours. After completion of the reaction, the hot solution was filtered three times to remove selenium, left overnight, and the selenium was again filtered off. By diluting the solution with water, diphenylbisglyoxal dihydrate was isolated, which was purified by crystallization from water. Yield of the reaction product 15–20%, melting point 78–82°C. Found, %: C 62.53; H 4.75. Calculated, %: C 63.57; H 4.60.
Synthesis of 4-iododiphenyl-2,2′-bisglyoxal. First, 2-iodophenanthrenequinone was prepared from phenanthrenequinone by direct iodination. For this purpose, to a mixture of 0.02 g-mol of phenanthrenequinone, 0.02 g-at of iodine, 50 ml of glacial acetic acid, and 5 ml of concentrated sulfuric acid, 2 ml of nitric acid, \(d = 1.4\), was gradually added at 80–90°C. The synthesis was continued with stirring for 4 hours. After completion of the reaction, the mixture was diluted with water; the precipitate of 2-iodophenanthrenequinone was filtered off, washed with water, and purified by crystallization from glacial acetic acid. Yield 25%, melting point 225°C.
4-Iododiphenyl-2,2′-bisglyoxal was obtained from 2-iodophenanthrenequinone without isolation of intermediates according to the following transformation scheme:
\[ \begin{array}{ccccc} \text{I} & \xrightarrow{\ \mathrm{CH_3MgI}\ } & \text{II} & \xrightarrow{\ \mathrm{O}\ } & \text{III} \\ & \xrightarrow{\ \mathrm{SeO_2}\ } & \text{IV} & \xrightarrow{\ \mathrm{H_2O}\ } & \text{V} \end{array} \]
where
\[ \begin{aligned} \text{I} &: \text{4-iododiphenyl-2,2′-dicarbonyl compound},\\ \text{II} &: \text{corresponding diol, } -\mathrm{CH(OH)CH_3},-\mathrm{CH(OH)CH_3},\\ \text{III} &: \text{4-iododiphenyl-2,2′-diacetyl, } -\mathrm{COCH_3},-\mathrm{COCH_3},\\ \text{IV} &: \text{4-iododiphenyl-2,2′-bisglyoxal, } -\mathrm{COCHO},-\mathrm{COCHO},\\ \text{V} &: \text{4-iododiphenyl-2,2′-bisglyoxal dihydrate, } -\mathrm{COCHO\cdot H_2O},-\mathrm{COCHO\cdot H_2O}. \end{aligned} \]
6.5 g of 2-iodophenanthrenequinone in 75–80 ml of absolute ether was introduced into the Grignard reagent prepared from 3.5 g of magnesium and 9 ml of methyl iodide. Then 50 ml of absolute benzene was added and the mixture was boiled for two hours. After completion of the reaction, the mixture was decomposed with acidified ice water; the reaction product was extracted with ether, the ether extracts were dried, and after distillation of the ether 2.1 g of a resinous substance was obtained (crude II). II was dissolved in glacial acetic acid, and at a temperature of 70°C 1.8 g of chromic anhydride in 20 ml of water was added. Oxidation time: 20 minutes. On cooling, crude 4-iododiphenyl-2,2′-diacetyl (III) precipitated. III in dioxane solution (40 ml) was oxidized at 70–100°C with a solution of 6.5 g of selenium dioxide in 50 ml of dioxane containing 2 ml of water for five hours. After completion of the reaction, selenium was filtered off, the mixture was diluted with water, and the precipitate was separated and recrystallized from dilute acetic acid. The yield of 4-iododiphenyl-2,2′-bisglyoxal dihydrate was 10–15%; melting point 72–78°C. Found, %: C 45.76; H 3.20; I 30.00. Calculated, %: C 44.86; H 3.04; I 29.67.
Conclusions
For the study of physiological properties, diphenyl-2,2′-bisglyoxal and 4-iododiphenyl-2,2′-bisglyoxal, not described in the literature, were synthesized.
Literature
- M. Ya. Kraft. ZhVKhO im. D. I. Mendeleeva, 10, 630 (1965).
- Hungarian patent 150155, RZhKhim., 12N262P (1966).
- U.S. patent 3146259, RZhKhim., 9N272P (1966).
- U Kan-yu, Van Lin, Tszyan San-tszyun, Khuan Lyan, “Yaosyue syuebao, Acta pharmas. sinica,” 12, No. 4, 254 (1965). RZhKhim., 24Zh236 (1966).
- Cavallini G., Nardi D. Boll. chim. farmac., 103, No. 10, 700 (1964), RZhKhim., 24Zh239 (1966).
- U.S. patent 3157698 (1964), RZhKhim., 21N308P (1966).
- U.S. patent 3097138 (1963), RZhKhim., 2N177P (1965).
- Hall D. M., Ladbary J. F., Lesslie M. S., Turner E. E. J. Chem. Soc., 3475 (1956).