PHENYL AND NAPHTHYL ESTERS OF 4(5)-NITROIMIDAZOLE-5(4)-CARBOXYLIC ACID

L. P. Kulev, L. S. Nikonova

Derivatives of 4(5)-nitroimidazole-5(4)-carboxylic acid have been described only scantily in the literature.

Of the esters of this acid, chiefly the esters of aliphatic alcohols [1, 2] have been studied; in experiments outside the organism they showed comparatively low antimicrobial activity.

Considering that the introduction of phenyl radicals may have a substantial influence on the properties of the esters in the direction of increasing this activity, we obtained esters of the general formula

\[ \begin{array}{c} XROOC{-}C{-}NH \\ \quad\quad\;\;\| \quad\quad \diagdown \\ O_2N{-}C{-}N{=}CH \end{array} \]

where \(R = C_6H_5,\ C_{10}H_7;\ x = Cl,\ NO_2\).

Nitroimidazolecarboxylic acid was obtained by the method developed by one of us jointly with A. M. Rozhkov and improved with R. N. Gireva [3, 4].

All the compounds described below were obtained by the interaction of the acid chloride of nitroimidazolecarboxylic acid with the corresponding phenolates according to the scheme

\[ \begin{array}{ccc} \begin{array}{c} NH{-}C{-}C\!\left(=O\right)Cl \\ \quad\;\;\| \\ HC\diagdown \quad C{-}NO_2 \\ \;\;\diagdown N \end{array} & +\ \dfrac{ROK}{-HCl}\ \longrightarrow & \begin{array}{c} NH{-}C{-}COOR \\ \quad\;\;\| \\ HC\diagdown \quad C{-}NO_2 \\ \;\;\diagdown N \end{array} \end{array} \]

The acid chloride was obtained by the action of thionyl chloride on nitroimidazolecarboxylic acid.

The esters are crystalline substances, very readily soluble in acetone and considerably less soluble in other common organic solvents; they do not form salts or complex compounds with mineral or organic acids. The UV spectra (Fig. 1) were obtained on an SF-4 spectrophotometer in acetone.

Introduction of a nitro group into the benzene ring of the ester leads to a shift of the absorption maximum toward shorter wavelengths: for the ortho- and meta-nitrophenyl esters by 280 Å and 250 Å, respectively, and for the para-nitrophenyl ester by 40 Å (Table 1). The characteristic absorption bands and the corresponding molecular extinction coefficients are given in Table 1.

Fig. 1. Ultraviolet absorption spectra. I—phenyl ester, II—o-nitrophenyl, III—m-nitrophenyl, IV—p-nitrophenyl, V—1-naphthyl, VI—2-naphthyl, VII—m-methylphenyl.

Table 1

Esters

\[ \begin{array}{c} \mathrm{ROOC\!-\!C\!-\!NH}\\ \mathrm{\ \ \ \ \ \ \ \Vert \ \ \ \backslash}\\ \mathrm{O_2N\!-\!C\!-\!N{>}CH} \end{array} \]

Experimental Part

Phenyl ester of 4(5)-nitroimidazole-5(4)-carboxylic acid (I). To a solution of potassium phenolate, obtained by the action of a 25% aqueous KOH solution on 1.61 g of phenol, 3 g of 4(5)-nitroimidazole-5(4)-carboxylic acid chloride are added, the mixture is stirred well for one hour at 50°, and it is left to stand for 5–6 hours in a thermostat at the same temperature. A small amount of water is added, the mixture is stirred, decanted, filtered, and the precipitate is dried first in air and then in a vacuum desiccator. After recrystallization from alcohol, 1.69 g (42% of theory) of the ester is obtained in the form of white lustrous crystals with m.p. 189.5–191°. Found, %: N 18.27. $C_{10}H_7O_4N_3$. Calculated, %: N 18.02.

o-Nitrophenyl ester (II). Obtained analogously to (I) from potassium o-nitrophenolate (calculated for 2.38 g of o-nitrophenol) and 3 g of nitroimidazolecarboxylic acid chloride; from alcohol, m.p. 194–195°. Yield 1.33 g (30% of theory). Found, %: N 19.79. $C_{10}H_6O_6N_4$. Calculated, %: N 20.14.

m-Nitrophenyl ester (III). Obtained analogously to (II). White crystals from alcohol, m.p. 195–197° (with decomposition). Yield 2.03 g (59.3% of theory). Found, %: N 20.39. $C_{10}H_6O_6N_4$. Calculated, %: N 20.14.

p-Nitrophenyl ester (IV). Obtained analogously to (II). White crystals from alcohol, m.p. 195–197° (with decomposition). Yield 2.03 g (42.7% of theory). Found, %: N 20.42. $C_{10}H_6O_6N_4$. Calculated, %: N 20.14.

m-Methylphenyl ester (V). Obtained analogously to (I) from 1.85 g of m-cresol. White crystals from alcohol, m.p. 204–204.5°. Found, %: N 16.59. $C_{11}H_9O_4N_3$. Calculated, %: N 17.00.

1-Naphthyl ester (VI). Obtained analogously to (I) from 2.47 g of 1-naphthol. Golden lustrous needles with m.p. 237–238° (with decomposition). Yield 3.68 g (76% of theory). Found, %: N 15.21. $C_{14}H_9O_4N_3$. Calculated, %: N 14.84.

2-Naphthyl ester (VII). Obtained analogously to (I) from 2.47 g of 2-naphthol. Lustrous needles with m.p. 219–220° (with decomposition). Yield 3.65 g (75.3% of theory). Found, %: N 15.16. $C_{14}H_9O_4N_3$. Calculated, %: N 14.84.

Conclusions

Phenyl, o-, m-, p-nitrophenyl, m-methylphenyl, and 1,2-naphthyl esters of 4(5)-nitroimidazole-5(4)-carboxylic acid have been obtained; their analysis was carried out and their UV absorption spectra were recorded.

Literature

1. Wind aus, Langenlen, Ber. 56, 683, 1923.
2. L. P. Kulev and A. M. Rozhkov. ZhOKh, 27, 1389, 1957.
3. L. P. Kulev and A. M. Rozhkov. Author’s certificate No. 109033, 1955.
4. L. P. Kulev and R. N. Gireva. ZhPKh, 30, 118, 1957.