RU1786037C - N-substituted phosphamides showing juvenile-hormonal activity - Google Patents

Abstract

SUMMARY OF THE INVENTION: The product is N-substituted phosphamides of CEP3-X-C6H40CH2CH2NHP (OXOC2H5) 2, where X-O, f), NOCH3. BP C18H24N05P, C19H24N05P, C2oH24N20sP. Yield 34-63%. Reagent 1: CHsONa, reagent 2: CeHs-X-CeH-jOH, where the X value is indicated above. Reagent 3: N-2-chloroethylaminodiethylphosphate. Reaction conditions: KJ, alcohol, DMF at boiling. 7 tab.

Description

enoxycarb at a concentration of 1.0 g / l only in 59% of the larvae.

The purpose of the invention is the preparation of new compounds, M-ethylaminodiethylphosphates. possessing higher juvenile o-hormonal activity, low toxicity for warm-blooded animals of man.

The goal is achieved by the synthesis of new compounds 1a-1c:

The corresponding phenol is treated with sodium methylate and then in the solution, the form of mid (M- (2-chloroethylamino) ethyl ethyl phosphate is formed. The corresponding 1M- (2-aroxyethylamino) diethyl phosphates (la-lb) are formed. Ib) hydrochloric acid O-methylhydroxylamine gives oxime (Ic). The obtained compounds are viscous, non-distillable In high vacuum liquids, which are purified by chromatography on a column of silica gel. The compounds are characterized by R f values on Sllufol UV 254, eluent - chloroform-methanol in a ratio of 9: 1.

. The structure of the compounds was proved using NMR spectra and elemental analysis. ,; :. .-.

The purity and individuality of the compounds were established using high performance liquid chromatography (10 cm column with Separon Cie reverse phase sorbent), eluent - acetonitrile - water in a 5: 1 ratio.

The resulting compounds (la-lc), their juvenile hormonal activity and acute toxicity to warm-blooded animals are illustrated by the examples below.

Tables 1 and 2 show the physicochemical properties of the compounds (laHc).

PRI me R 1. (4-Phenoxyphenoxy) ethylamino diethyl phosphate (la).

2.00 g of 4-phenoxyphenol in 3 ml of methanol is treated with sodium methylate. The resulting solution is the dissolution of 0.3 g of sodium in 3 ml of methanol. The resulting sodium phenolate solution was evaporated in vacuo, the residue was dissolved in 10 ml of dimethylformamide, 2.0 g of M- (2-chloroethylamine) diethyl phosphate, 0.1-0.2 g of potassium iodide were added and the mixture was boiled for 5 hours. Then the mixture is cooled, poured into 50 ml of water, extracted with ethyl acetate, the extracts are washed with 5% potassium hydroxide solution, saturated sodium chloride solution, dried with sodium sulfate, the ethyl acetate is evaporated, the residue is chromatographed on a column, the carrier is SHIcagel L 100 / 160 t, eluent ethyl acetate. Yield 1.50 g. Similarly, compound (Ib) was obtained.

0-Methyl-4- 2- (diethoxyphosphorimidoyl) - ethoxy benzophenonoxime (Ic).

To 2.0 g of (4-benzenephenoxy) ethylamino diethyl phosphate (Ib) in 8 ml of methanol was added 0.85 g of 0-methylhydroxylamine hydrochloride and 0.80 ml of pyridine and the mixture was boiled

for 3.0 hours. The mixture was then cooled, the methanol was evaporated in vacuo, water was added to the residue and acidified with dilute hydrochloric acid to pH 1-2. It was extracted with ethyl acetate, the extract was washed with saturated sodium chloride solution, and dried with sodium sulfate. Ethyl acetate was evaporated, the residue was chromatographed on a column, the carrier was Sillcagel L 100/160 / g, and the eluent was ethyl acetate. Yield 1.70 g. Properties 1a-1c are given in table 5. 1 and 2.

Example 3. The effect of the compounds on the large flour hrushchak (laboratory experience).

The study of juvenile hormonal

0 act. In Petri dishes, 1 ml of solutions of compounds of a certain concentration are applied to filter paper. Larvae of the last flour hrushchak of the last age are placed in the cups before pupation in the amount of 10-15 pieces each. The repetition of the experiments is threefold. The prototype — phenoxycarb — serves as a reference; control — a variant of experience without the use of drugs.

0 Experimental cups are kept in a thermostat at an air temperature of 22-23 ° C and a relative humidity of 60%. Analysis of the experiment is carried out on the 21st day after the bookmark of the experiment, Juvenile hormonal activity

5 compounds are determined by the number of ugly adults and pest pupae and are expressed as a percentage relative to the control.

The experimental data are presented in table. 3.

0 It has been established / that the compounds (la-lc) have juvenile hormonal effects on large flour flies and the level of action is superior to the phenoxycarb prototype.

5 PRI me R 4, The effect of compounds on field crickets (laboratory experience).

The procedure for laying the experiment is similar to that described in Example 3. However, in this case, insects are treated topically. Solutions of compounds of a certain concentration are applied to the anterior back of larvae of the last age. Compounds (la-lc) were found to have juvenile hormonal effects and the phenoxycarb standard exceeded the level of 5.

The experimental data are presented in table 4. Example 5, The effect of compounds on. Colorado potato beetle (laboratory experience).

The methodology for laying the experience is similar to that described in example 3.

Table 1

 Compounds (la-lc) of the formula

I OCHjCHjNHP Hs

PMR and NMR 31 P spectra of compounds (la-lc) (d, ppm, J, Hz, CDCIa) of the general formula:

P

OSNgSN2MNR (OSgN5) g

List of abbreviations: t-triplet. m-multiplet.

Juvenile-hormonal action of compounds on the large mealworm

table 2

Table 3

Juveni - the hormone action of compounds on field crickets

Juvenile hormonal activity of compound (Ib) on a Colorado potato beetle

Juvenile hormonal effects of compounds on a cotton scoop

Table a

Table 5

Table 6

Juvenile hormonal effects of compounds on the American white butterfly

Table 7