SYNTHESIS OF SOME DERIVATIVES OF 2′-FORMYLBIPHENYL-2-CARBOXYLIC ACID

I. L. KHALFINA, G. N. SHABALINA

(Presented by the scientific seminar of the departments and laboratories of organic synthesis)

2′-Formylbiphenyl-2-carboxylic acid (aldehydo acid) is of great interest as an intermediate product for obtaining biologically active compounds and other practically important substances [1, 2, 3]. On its basis we obtained a series of oximes of complex alkyl esters of 2′-formylbiphenyl-2-carboxylic acid of the general formula [4]

\[ \begin{array}{c} \text{[[structural formula: biphenyl system bearing } -\mathrm{C(=O)OR} \text{ and } -\mathrm{CH{=}N{-}OH}\text{ substituents]]} \end{array} \]

\[ \begin{aligned} R &= \mathrm{H},\quad \mathrm{CH_3},\quad \mathrm{C_2H_5},\quad \mathrm{H{-}C_3H_7},\\ &\quad I \qquad II \qquad III \qquad IV\\ &= i\text{-}\mathrm{C_3H_7},\quad \mathrm{H{-}C_4H_9},\quad i\text{-}\mathrm{C_4H_9},\quad i\text{-}\mathrm{C_5H_{11}}.\\ &\quad V \qquad VI \qquad VII \qquad VIII \end{aligned} \]

Compounds IV, VI, and VII, in their fungitoxicity, are not inferior to the known fungicide 2,3-dichloro-1,4-naphthoquinone (phyton), taken as a standard [Table 1]. A major advantage of the synthesized substances is their low toxicity for warm-blooded animals.

Table 1

In connection with the above, the aim of the present work was to investigate the synthesis of the oxime of the isobutyl ester of the aldehydo acid with the purpose

finding conditions under which it could be obtained in as high a yield as possible.

At the first stage of the work, a systematic study was carried out of the influence of the following factors on the yield of the isobutyl ester of the aldehyde acid: the temperature and duration of the reaction, and the type and amount of catalyst. The results of the experiments are given in Table 2.

Table 2

* Four different catalysts were tested; the best results were obtained when sulfuric acid was used.

The synthesis of the ester was carried out under conditions in which esterification, rather than acetalization, could proceed preferentially. Experiments were also performed under conditions in which the acetalization reaction could proceed preferentially. In this case, anhydrous copper sulfate and gaseous hydrogen chloride were used as the catalyst; the reaction mixture was heated for 40–50 h, and a 10-fold excess of alcohol relative to the starting acid was used. As shown by elemental analysis of the product obtained, the result of determination of the saponification number, and also the infrared spectrum, in all cases the isobutyl ester of the aldehyde acid was obtained (when copper sulfate was used, the starting aldehyde acid was isolated). It is possible that acetalization of diphenyl aldehydes proceeds with still greater difficulty than acetalization of benzene aldehydes [3]. The preferential course of the esterification reaction in the present case is in good agreement with current ideas concerning the mechanism of the acetalization and ether-formation reactions.

At the second stage of the work, the influence of reaction duration and of the ratios of the reagents taken on the yield of the oxime of the isobutyl ester of the aldehyde acid was studied. The results of the experiments are given in Table 3.

Table 3

Under the optimal conditions obtained, oximes of other esters of the aldehydo acid were synthesized; data on them are given in Table 4.

Table 4

Compounds of the general formula

$$ \begin{array}{c} \text{biphenyl skeleton bearing }-\mathrm{C(=O)OR}\text{ and }-\mathrm{C(=R')H} \end{array} $$

2′-Formylbiphenyl-2-carboxylic acid was obtained from the products of ozonolysis of phenanthrene and had m.p. 130–132°C [5].

Experimental Part

Isobutyl ester of the aldehydo acid. 5 g (0.022 g mol) of dry aldehydo acid, 41 ml (0.44 g mol) of isobutyl alcohol, and 0.143 ml (0.0027 g mol) of sulfuric acid (specific gravity 1.84) are heated for 6 h in an oil bath. The reaction mixture is then poured into water, treated with sodium carbonate solution, and washed with water. The product is purified by distillation under vacuum. The isobutyl ester of the aldehydo acid is a yellowish oily liquid with b.p. 230°C at 13 mm Hg. The yield is 94%.

Oxime of the isobutyl ester of the aldehydo acid. 2.82 g (0.01 g mol) of the isobutyl ester of the aldehydo acid, previously dissolved in alcohol, 2.085 g (0.03 g mol) of hydroxylamine hydrochloride, 10.8 ml of 10% sodium hydroxide solution, and 30 ml of ethanol are heated for three hours. After the reaction mixture is cooled and a small amount of hydrochloric acid is added, a yellowish oil precipitates; it is purified by distillation under vacuum. The pure oxime has b.p. 210°C at 3 mm Hg. The yield is 96%.

1. The influence of various factors on the synthesis of the isobutyl ester of the aldehydo acid and its oxime was studied.

2. Optimal conditions were found for the synthesis of certain derivatives of the aldehydo acid, making it possible to obtain them in high yields.

3. It was shown that, under the adopted conditions for the synthesis of the ester of the aldehydo acid, only the esterification reaction occurs, and not acetalization.

REFERENCES

1. Author’s Certificate No. B1468.
2. I. L. Khalfina. Journal of the All-Union Chemical Society named after D. I. Mendeleev, vol. 12, No. 6, 1967.
3. I. L. Khalfina. BAS, 1963.
4. A. G. Pechenkin, I. L. Khalfina. Journal of the All-Union Chemical Society named after D. I. Mendeleev, vol. 8, No. 6, 1963.
5. P. S. Beiley, J. Am. Chem. Soc., 78, 3811, 1956.