RU2105771C1 - 2-alkoxy-2-thio-5-(n-phenylcarbamoyl) - Google Patents

Abstract

FIELD: agriculture, more particularly seed. SUBSTANCE: products: 2-alkoxy-2-thio-5-(N-phenylcarbamoyl-6-methyl- 1,4,2-oxathiaphosphines of formula I: CH₃ wherein R is C₂H₅, C₃H₇ or iso-

Description

где
R CH₃ (I), C₂H₅ (II), i-C₃H₇ (III)
Соединения I III обладают биологической активностью и могут быть использованы в сельском хозяйстве, преимущественно в качестве протравителей семян.2-alkoxy-2-thio-5- (N-phenylcarbamoyl) -6-methyl-1,4,2-oxathiaphosphorins
The invention relates to the chemistry of organophosphorus compounds, in particular to new phosphorus-containing heterocyclic compounds 2-alkoxy-2-thio-5- (N-phenylcarbamoyl) -6-methyl-1,4,2-oxathiaphosphorins of the general formula

Where
R CH ₃ (I), C ₂ H ₅ (II), iC ₃ H ₇ (III)
Compounds I III have biological activity and can be used in agriculture, mainly as seed dressers.

R имеет вышеуказанные значения.These compounds can be obtained from readily available dithiadiphosphetidine as a result of a series of successive transformations: alcoholysis, alkylation of the intermediate triethylamine salt of chloromethyl-0-ethyldithiophosphonic acid with an anilide of α-chloroacetoacetic acid, and subsequent cyclization under the action of a base of the obtained a - (0-ethylosylphthylmethyl) anilide acetoacetic acid, accompanied by 1,4-S, O migration of the phosphoryl group. The listed sequence of transformations is presented in the following diagram:

R has the above meanings.

 The structure of the obtained compounds was confirmed by elemental analysis and the data of PMR and NMR spectra.

 Biological activity was evaluated in the field experiments using the example of compound II, conditionally called "foscarboxin". Tests have shown that foscarboxin, in addition to the fungicidal effect on pathogens, has a positive effect on the development of the root system and the growth of the aerial part of the seedling. Young plants more intensively formed the root system. The length of the main root on barley in the variant with foscarboxin is 25-30% longer than in the variant with ethanol. This has contributed to better absorption of nutrients. The length of the seedlings when tested on barley was 50% higher compared to the standard. It was also found that the drug has a beneficial effect on growth factors that determine the yield, for example, the formation of side shoots and plant density. The plant standing density in the variant with foscarboxin was 24–50% higher than in the control (without seed treatment) and 9–40% higher than in the variants with standards. The tillering coefficient in barley crops was 2 times higher than in control and 1.5 times higher than in variants with standards.

 Foscarboxin at a rate of consumption of 1.0 and 1.5 kg of active substance per ton of seeds exceeded the standards in activity against smut smut by 20 23% against root rot by 30 40% and in yield increases by 4 5 c / ha.

Compounds I III are low toxic for warm-blooded animals: LD ₅₀ when tested in mice> 2000 mg / kg.

 The range of organophosphorus pesticides, including derivatives of thiophosphoric and thiophosphonic acids, possessing various types of activity, is extremely large. In this sense, it is appropriate to refer to one of the reviews, for example, V.K. Promonenkov et al. Published in the collection "Results of Science and Technology", series Organic Chemistry, vol. M.I. Kabachnik. - M. VINITI, 1989, p. 3, as well as the monograph by N. Melnikov. Pesticides -M. Chemistry, 1987, p. 400.

[1]
Известны фосфорсодержащие гетероциклические соединения, в том числе замещенные 1,3,2-оксатиафосфоринаны

где
R CH₃ и C₂H₅ и другие,
обладающие активностью против членистоногих и нематод [2]
В [3] описан замещенный 1,3,2-оксазафосфоринан

проявляющий активность против галловых нематод.As for heterocyclic phosphorus-containing compounds, among them also quite a lot of compounds with pesticidal activity are known, for example, the insecticide salition

[1]
Known phosphorus-containing heterocyclic compounds, including substituted 1,3,2-oxathiaphosphorinans

Where
R CH ₃ and C ₂ H ₅ and others,
possessing activity against arthropods and nematodes [2]
In [3], substituted 1,3,2-oxazaphosphorinan is described.

showing activity against gall nematodes.

где
R C₂H₅O, R'-H, R''-трет-C₄H₉;
R-(C₂H₅)₂N, R'-H, R''-2,4,5-Cl₃C₆H₂;
R-C₂H₅O, R'-COOC₂H₅, R''-CH₃,
и другие описаны в [4]
Проведенные биологические испытания не выявили, однако, среди них перспективных для дальнейшей разработки препаратов.The closest structural analogues, namely oxathiophosphorins having the formula

Where
RC ₂ H ₅ O, R'-H, R '' - t-C ₄ H ₉ ;
R- (C ₂ H ₅ ) ₂ N, R'-H, R '' - 2,4,5-Cl ₃ C ₆ H ₂ ;
RC ₂ H ₅ O, R'-COOC ₂ H ₅ , R '' - CH ₃ ,
and others are described in [4]
The conducted biological tests did not reveal, however, among them promising for further development of drugs.

 Another structural and at the same time functional analogue of the compounds designated as an object of the present invention is the well-known 2,3-dihydro-6-methyl-5-phenyl-1,4-oxathinine (carboxine) active ingredient of the drug Vitavax (Uniroyal) and a number of other drugs.

содержащий в цикле вместо фосфорорганического фрагмента углеводородный [1, с. 251]
По биологической активности соединения I III оказались близкими именно к карбоксину. Поэтому препараты на его основе были взяты в качестве эталонов. Как показали испытания, вновь синтезированные соединения имеют определенные преимущества по сравнению с известными, о чем уже было упомянуто выше.

containing in the cycle instead of organophosphorus fragment hydrocarbon [1, p. 251]
The biological activity of compounds I III turned out to be close to carboxin. Therefore, preparations based on it were taken as standards. As tests have shown, newly synthesized compounds have certain advantages over known ones, as was already mentioned above.

 Example 1. 2-Chloromethylethoxythiophosphonylthioacetoacetanilide.

To a suspension of 2.89 g (0.01 mol) of bis-chloromethyldithiodiphosphetidine in 10 ml of absolute benzene was added a solution of 2.02 g (0.02 mol) of triethylamine, 5 ml of ethyl alcohol in 10 ml of absolute benzene. The mixture was stirred for 30 min at 20 ^° C, and then 4.23 g (0.02 mol) of 2-chloroacetoacetanilide was added, the reaction mass was left overnight, the precipitate of triethylamine hydrochloride was filtered off, the solvent was removed in vacuo. The residue was purified by column chromatography on silica gel, solvent: petroleum ether-ethyl acetate, 8: 1. 4.2 g of 2-chloromethylethoxythiophosphonylthioacetoacetanilide were obtained. Yield 58% T _mp 70 ^° C.

Found, N 3.54; S 17.23;
C ₁₃ H ₁₇ ClNO ₃ O ₃ PS ₂ .

 Calculated, N 3.83; S 17.53.

 Example 2. 2-Ethoxy-2-thio-5- (N-phenylcarbamoyl) -6-methyl-1,4,2-oxathiaphosphorin (II).

To a suspension of 1.24 g (0.011 mol) of potassium tert-butylate in THF was added dropwise 4.05 g (0.011 mol) of 2-chloromethylethoxythiophosphonylthioacetoacetanilide in THF at 5 ^° C. and stirred for 5 hours at 20 ^° C., the precipitate was filtered off, the solvent was filtered. removed in vacuo. The residue was crystallized from hexane with ethyl acetate.

2.7 g of 2-ethoxy-2-thio-5- (N-phenylcarbamoyl) -6-methyl-1,4,2-oxathiophosphorin are obtained. Yield 75% T _pl 110 112 ^o C.

 Found C, 47.13; H 4.86; N 3.78; P 9.76.

C ₁₃ H ₁₆ NO ₃ PS ₂
Calculated, C 47.40; H 4.00; N, 4.25; P, 9.40.

 Similarly obtained compounds I and III.

2-Methoxy-2-thio-5- (N-phenylcarbamoyl) -6-methyl-1,4,2-oxathiaphosphorin (I). Yield 20% T _mp 119 120 ^o C.

 Found C 45.46; H 4.19; P, 9.70; S 20.32.

C ₁₂ H ₁₄ NO ₃ PS ₂ .

 Calculated, C 45.70; H 4.47; P 9.82; S 20.33.

2-Isopropoxy-2-thio-5- (N-phenylcarbamoyl) -6-methyl-1,4,2-oxathiaphosphorin (III). Yield 80% T _pl 82 84 ^o C.

 Found, N 3.85; P 9.35; S 19.17.

C ₁₄ H ₁₈ NO ₃ PS ₂ .

 Calculated N 4.08; P 9.02; S 18.67.

In the 1H NMR spectra of compounds I III, along with signals of protons of alkoxyl groups at the phosphorus atom, signals of protons of the methyl group were observed in the region of 2.15 ppm. in the region of 9.4 ppm there were signals of NH protons, and in the region of 7.1 7.7 ppm. aromatic protons. Nonequivalent methylene protons of the hetero ring appeared in the region of 3.30 3.53 ppm. as an ABX system (J _HH 14.8; J _PH 11.0; J _PH 2.2 Hz). In the ³¹ P NMR spectra in the region of 83.0 ppm characteristic of thiophosphonic acid esters, a singlet signal was observed, while for the initial dithiophosphonates it was located in a weaker field (δ _p 95 ppm).

 Example 3. The biological and economic effectiveness of foscarboxin as a seed dresser for cereals.

 Testing Methodology.

 Field experiments were conducted in the Moscow region on spring barley of the Moskovsky-3 variety against dust smut (Ustilago nuda, U. nigra) and root rot caused by fungi of the genus Helminthosporium (H. Sativum, H. teres) and Fusarium spp. The experiments were carried out according to the generally accepted methodology of the NIIKhSZR (methodical guide for conducting greenhouse-field tests of seed dressers, fungicides and bactericides, Cherkasy, 1996).

Foscarboxin was tested at a rate of consumption of 1.0 and 1.5 kg / t of seeds for the active substance (AI)
Vitavax (carboxin) and phenox (carboxin) were taken as ethanol at a rate of consumption of 1.5 kg / t of seeds according to AI Vitatiuram (carboxin + thiram) 1.6 kg / t seeds

Harvested by trial sheaf. In each variant, 5 sheaves with an area of 0.5 m ^{2 were} used for yield analysis.

Before etching, the seeds were analyzed for infection by pathogens of seed infection according to the generally accepted method. As a result, the following composition of the pathogenic complex was revealed,
Bipolaris spp. 14
Fusarium spp. 14
Penicillium spp. 5
Bacterioses 3.

 The test results are given in table. fourteen.

Claims (1)

2-alkoxy-2-thio-5- (N-phenylcarbamoyl) -6-methyl-1,4,2-oxathiaphosphorins of the general formula

where R CH ₃ (I); C ₂ H ₅ (II); i C ₃ H ₇ (III).

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