On the Relationship between the Structure and Insecticidal Activity of Certain Azo Derivatives of Salicylic and α-Oxynaphthoic Acids

L. P. Kulev, N. A. Mukhina

Among the large number of organic compounds tested as insecticides, azo derivatives have shown high toxicity toward certain species of insects. Thus, azobenzene proved active against phytophagous mites that are not affected by other insecticides [1, 2].

As intestinal insecticides, p-aminoazobenzene—especially in the form of the hydrochloride—and p-bromo- and p-iodo-substituted azobenzenes have shown good results [3, 4]. According to the patent literature [5, 6, 7], other azo compounds, including those with an azo group bonded to the nitrogen of a heterocycle, also possess high insecticidal activity.

However, information on the mechanism of the insecticidal action of azo derivatives is absent from the literature.

Of all organic insecticides, DDT and certain phosphorus-containing compounds are the most thoroughly studied in this respect. The insecticidal activity of DDT is associated with sorption phenomena and with the suppression of enzymatic oxidative processes in the insect organism [8]. It is believed that the activity of organophosphorus compounds is due to the fact that the insecticide suppresses the action of the enzyme cholinesterase, binding firmly to it through forces of intermolecular interaction [9].

Taking into account that the hemoglobin and enzyme systems of insects contain metals—above all iron—it may be assumed that the insecticidal activity of organic compounds is connected with their ability to interact with these metals, for example as a result of complex formation. Hence the insecticidal activity of azo derivatives should increase if their molecules contain strong complex-forming groups capable of firmly binding the metal of the insect enzyme in the form of an inner-complex salt. Such groups may be the hydroxyl and carboxyl groups, situated in the ortho position with respect to one another.

On the basis of these considerations, our aim was to obtain a series of azo derivatives of salicylic and α-oxynaphthoic acids of the type

\[ \mathrm{HOOC}\ \ \mathrm{HO}\ \ \text{(benzene ring)}\ \mathrm{N{=}N{-}ArX} \]

\[ \mathrm{HOOC}\ \ \mathrm{HO}\ \ \text{(naphthalene ring)}\ \mathrm{N{=}N{-}ArX} \]

and to compare them with one another with respect to insecticidal activity.

The indicated azo dyes were obtained by the usual methods, by coupling diazotized amines with salicylic and $\alpha$-hydroxynaphthoic acids.

Preliminary tests to determine relative insecticidal activity were carried out under the direction of A. V. Kovalenok, docent of the Department of Invertebrate Zoology of Tomsk State University. The tests were performed on grasshoppers of the genus Chorthippus according to standard methods for intestinal insecticides.

Azo derivatives of salicylic acid proved to be somewhat more active than the analogous derivatives of $\alpha$-hydroxynaphthoic acid. Replacement of the benzene ring in the diazo component of benzeneazo-$\alpha$-hydroxynaphthoic acid by a naphthalene ring ($\alpha$-position), and also the introduction of a halogen into the para position of the diazo component, leads to a certain increase in insecticidal activity. Introduction of alkyl radicals and of the nitro group into the meta or para position of the diazo component of azo derivatives of $\alpha$-hydroxynaphthoic acid almost does not change the activity of the preparation. With the introduction of an amino group or a complex ether grouping into the para position of the diazo component, however, the activity of the preparation is markedly reduced.

It should be noted that azo derivatives of phenol and naphthol (Table, Nos. 28, 29), which are not capable of forming inner-complex salts, proved to be much less active than the corresponding azo derivatives of salicylic and $\alpha$-hydroxynaphthoic acids.

These data confirm the idea we expressed regarding the dependence between toxicity and the ability of azo derivatives of the above-mentioned type to form inner-complex compounds.

Experimental Part

p-Iodobenzeneazosalicylic acid (I)

Obtained analogously to p-nitrobenzeneazosalicylic acid [10, 11] from 20 g of p-iodoaniline and 12 g of salicylic acid. Yield of the Na salt 24.2 g (72%). The free acid is a light-brown powder. M.p. 233–234° (with decomp.). Soluble, like all the compounds described below, in alcohol, acetone, and glacial acetic acid.

p-Bromobenzeneazosalicylic acid (II)

Obtained analogously to (I) from 5 g of p-bromoaniline and 3.9 g of salicylic acid. Yield of the Na salt 6.06 g (65%).

The free acid forms light-brown needles. M.p. 234–236° (with decomp.).

p-Bromobenzeneazo-$\alpha$-hydroxynaphthoic acid (III)

Obtained analogously to (I) from 3 g of p-bromoaniline and 3.27 g of $\alpha$-hydroxynaphthoic acid. Yield of the Na salt 4.08 g (63%). The free acid is a red-brown powder. M.p. 222° (with decomp.).

p-Chlorobenzeneazo-$\alpha$-hydroxynaphthoic acid (IV)

Obtained analogously to (I) from 10 g of p-chloroaniline and 14 g of $\alpha$-hydroxynaphthoic acid. Yield of the Na salt 23.7 g (84%). The free acid forms small green crystals. M.p. 201–203° (with decomp.).

p-Iodobenzeneazo—α-hydroxynaphthoic acid (V)

Obtained analogously to (I) from 10 g of p-iodoaniline and 8.5 g of α-hydroxynaphthoic acid. Yield of the Na salt 17.5 g (87.5%). The free acid—dark-green crystals. M.p. 208° (with decomp.).

Ethyl ester of p-carboxybenzeneazosalicylic acid (VI)

Obtained analogously to p-ethoxybenzeneazosalicylic acid [12] from 10 g of anesthesin and 8.3 g of salicylic acid. Yield of the Na salt 13.8 g (72.5%). The free acid—yellow needles. M.p. 208–209° (with decomp.).

o-Methyl (VII), m-methyl (VIII), p-methyl (IX)—benzeneazo-α-hydroxynaphthoic acids

Obtained analogously to (VI) from 10 g of the corresponding toluidine and 17.5 g of α-hydroxynaphthoic acid. Yields of the Na salts, respectively: 28 g (98%), 26.7 g (84%), 28.4 g (90%). M.p. 184–185°, 193–194°, 209° (with decomp.). VII—brown; VIII and IX—greenish crystals.

Ethyl ester of p-carboxybenzeneazo—α-hydroxynaphthoic acid (X)

Obtained analogously to (VI) from 10 g of anesthesin and 11.2 g of α-hydroxynaphthoic acid. Yield of the Na salt 9.9 g (45%). The free acid—dark-brown powder. M.p. 208° (with decomp.).

β-Naphthylazosalicylic acid (XI)

Obtained analogously to (VI) from 10 g of β-naphthylamine and 9.6 g of salicylic acid. Yield of the Na salt 10 g (43%). The free acid—gray powder. M.p. 230° (with decomp.).

β-Naphthylazo—α-hydroxynaphthoic acid (XII)

Obtained from 10 g of β-naphthylamine and 13.1 g of α-hydroxynaphthoic acid. Yield of the Na salt 21.75 g (84%). The free acid—dark-brown powder. M.p. 209° (with decomp.).

p-Aminobenzeneazo—α-hydroxynaphthoic acid (XIII)

Obtained by reduction with sodium sulfide of 10 g of p-nitrobenzeneazo—α-hydroxynaphthoic acid, analogously to the reduction of azo dyes containing a nitro group (13). Yield of the Na salt 7 g (76%). The free acid—black powder. M.p. 263° (with decomp.).

Conclusions

1. Thirteen azo derivatives of salicylic and α-hydroxynaphthoic acids not previously described in the literature have been obtained; they have been analyzed and their comparative insecticidal activity has been determined.

2. Azo derivatives of salicylic acid are somewhat more active than the corresponding derivatives of α-hydroxynaphthoic acid. Introduction of substituents, especially halogens or fatty hydrocarbon radicals, into the benzene ring of the diazo component promotes an increase in the insecticidal activity of the azo compounds; the most toxic to insects in this series proved to be p-bromobenzeneazosalicylic acid.

Table

Comparative insecticidal activity of azo derivatives of salicylic and α-hydroxynaphthoic acids

1. It has been shown that azo dyes containing a hydroxyl and a carboxyl group in the azo component are considerably more active than the corresponding azo dyes having only one hydroxyl group (azo derivatives of phenol and naphthol), i.e., those incapable of forming intracomplex salts.

LITERATURE

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