SU1292667A3 - Method of producing substituted tetrazines - Google Patents

Abstract

The invention relates to substituted tetrazines, in particular compounds of the general formula R, C N-N CRj-NR, -NR4 (I), where R is cyclo-C H ,, or phenyl monosubstituted with a halogen or a lower alkyl; R is 2-halo-phenyl; K and R are the same or different, H, C.-C, is alkyl or R and R are a simple bond that exhibits acancidal activity and can be used for prophylaxis and tick infestation by eggs or larvae, as well as by infection of plants, animals or soil. To detect the activity of compounds among substituted tetrazines, new G were obtained. Their synthesis is carried out from hydrazine substituted by R HR, which have the indicated meanings, and substituted by R, and R by dichlorazine, where R and R are indicated above, at 30-100 & ° C in a solvent, for example ethanol, followed by, if necessary, treatment of 1,2-dihydrotetrazine with an oxidizing agent — NaNO ,, HNO ,, bromine or hydrogen peroxide, in a solvent — CH 2 С (0) HE, chloroform or ethanol . Tests show that they exhibit acaricidal activity better than dicofol or amatraz. Also active against Persian aphids. 1 tab. § (W sn

Description

obtaining new substituted general formula

N-is

Un.

Yazch.

Ik

and

R ,, that can be one

2

where r

common or different - hydrogen, an alkyl residue containing -3 am carbon,

or R, and R together is a simple bond; a cyclohexyl group or pheny substituted by one halogen atom or lower alkyl; K is a phenyl group, substituted in the second position with halogen, possessing acaricidal activity.

The purpose of the invention is to develop a method for obtaining new tetrazine derivatives having a new type of activity in this class of chemical compounds, namely, acaricidal activity.

Example 1. Get 3,6-bis (2-chl Lrphenyl) -1,2-DIGIDRS-1-methyl- -152, 4,5-tetrazine,

a.N, N -bis (2-chlorobenzoyl) hydrazine,

A solution of hydrazine hydrate (25 g) in water (300 ml) is treated with stirring dropwise simultaneously with a solution of sodium hydroxide (43.6 g) in water (150 ml) and 2-chlorobenzoyl chloride (180.25 g) “After this mixture is further stirred at room temperature for 2 hours. The precipitate is filtered, washed with acetone / water: 1 and recrystallized from acetic acid. Output 97.5 g, so pl. 217-219 p.

b.bis (on, 2-dichlorobenzoylidene) hydrazine.

P-chloride phosphorus (443.5 g) is heated to 110 ° C in 1,2-d-chlorobenzene (850 ml). N, N -bis (2-chlorobenzoyl) hydrazine (164.7 g) is added in portions to the stirred solution. After this, the mixture is additionally stirred for 1 hour at 110 ° C: After that, excess phosphorus pentachloride and 1,2-dichlorobenzene are distilled off. under reduced pressure to form a hardening oil, which is recrystallized from methanol,

ten

25

thirty

i5 0

33

40

45

50

55

(uL, 2-dichles; rbsnzilden) of hydrazine in the form of a cris1-allic powder, m.p. 05-107 C,

c, 3 i, 6-bis (2-chlorophenyl) -I, 2-di-hydro-1-methyl-1,2,4,5-tetrazine.

Methylhydrazine (31.0 g) in ethanol (550 ml) is heated under reflux to 78 ° C and treated in portions of bis; (vol, 2-dichloro-13-ylidene) hydrazine (fi8.0 g). Thereafter, the mixture is further refluxed for 1/2 hour.

The ethanol is evaporated in vacuo and the precipitate is washed with water. Recrystallization of the precipitate from the water-ethanol mixture yields 37.0 g of product with a mp. 116-118 ° C.

Example s 2-4. The following compounds are modified according to example 1, but when using the corresponding orthohalobenzoyl chlorides at stage Q and the corresponding hydrazines or substituted hydrazines at stage b, the processing temperatures are 30, 70 and 100 ° C, and the solvent is methanol , ethanol, tetrahydrofuran, acetonitrile, toluene, dioxa, and petroleum ether:

2 „3,6-bis (chlorophenyl) -, 2-dihydro-152,4,5-tetrazine, so pl. 168-9 ° C;

3. 3, 6-bis (2-sperphenyl) -1, 2-di-1, ido-1 -methyl-1., 2,4,5-tetrazine, m.p. 93-94 ° C;

4 „3,6-bis (2-fluorophenyl) -, 2-di-hydro-i, 2,4,5-tetrazine, m.p. 145-1484.

Example 5 "3- (4-methylphenyl) -6- (2-chlorophenyl) -1,2-dihydro-1-methyl-1,2,4,5-tetrazine is obtained,

a, N- (2-chlorobenzosh1) -N - 4- / methylbenzoyl. 1. hydrazine.

2-Chlorobenzhydrazide (38.8 g) is dissolved in caustic soda solution (9.18 g) in a syde (125 ml). 4-methylbenzoyl chloride (35.2 g) is added dropwise to the solution while stirring. The mixture is then stirred for 2 hours, the precipitated precipitate is filtered off, washed with water and recrystallized from ethanol to form 30.0 g of the desired product, m.p., 204-206 ° C,

in, 3 (4-1ethylphenyl) -6- (2-chloro-FtHj:) -, 2-DIHYDRO - 1-methyl-, 2,4,5-tetrazine.

As described in example 1 (stages b and s) 5, the desired product is used when using the product of stage a of the present example, t, pl. 152-154 ° C.

Examples 6-12. As described in Example 5, the following compounds are obtained using methanol, ethanol, tetrahydrofuran, acetonitrile, toluene, dioxane, and petroleum ether as the solvent in the last step:

6.3- (A-methylphenyl) -6- (2-chlorophenyl) -1,2-dihydro-1,2,4,5-tetrazine, m.p. 194-197 ° C;

7.3-tert-butsh-6- (2-chlorophenyl) -1,2-dihydro-1,2,4,5-tetrazine, m.p. 172-174 ° C;

8.3-tert-butsh-1-6- (2-chlorophenyl) -1,2-dihydro-1 (or 2) -methyl-1,2,4,5 tetrazine, m.p. 105-120 ° C;

9. З-phenyl-6- (2-chlorophenyl) -1,2- -dihydro-1,2,4,5-tetrazine, mp, 206-210 ° C;

10.3- (2-fluorophenyl) -6- (2-chlorophenyl) -, 2-dihydro-1 (or 2) -methyl -1,2,4,5-tetrazine, m.p. 95-97 ° C;

11.3- (3-methylphenyl) -6- (2-chlorophenyl) -1,2-dihydro- (or 2) -g1methyl -1 -1, 2,4,5-tetrazine, m.p. 163-165 seconds;

12.3- (2-Bromophenyl) -6- (2-chlorophenyl) -1, 2-dihydro-1 (or 2) -methyl -1,2,4,5-tetrazine, m.p. 102-104 ° C.

Example 13. Get 3,6- -bis (2-chlorophenyl) -I, 2,4,5-tetrazine.

Dihydrotetrazine, prepared in Example 2 (0.8 g), was dissolved in glacial acetic acid (50 ml) and a solution of 2.0 g of sodium nitrate in 10 ml of water was added dropwise with stirring. After that, the mixture is poured into water and the solid precipitate is removed from the filter. After recrystallization from ethyl acetate, a product is obtained with m.p. 179-182 ° C.

Examples 14-17.In accordance with example 13, the following compounds are obtained (using nitric acid, bromine and hydrogen peroxide as the oxidizing agent, and acetic acid, carbon tetrachloride and ethanol as the solvent) of the corresponding 1,2-dihydrotetrazines :

14.3-tert-butyl-6- (2-chlorofensh1) - -I, 2,4,5-tetrazine, so pl. 86-90 ° C;

15. 3-phenyl-6- (2-chlorophenyl) -,. -1,2,4,5-tetrazine, m.p. 120-122 ° C;

16.3- (2-bromophenyl) -6- (2-chlorophenyl) -1, 2,4,5-tetrazii, mp.1 66-168 С

O

five

0

five

0

five

0

five

0

five

17.3- (4-methylphenyl) -6- (2-chlorophenyl) -, 2,4,5-tetrazine, m.p. 129-132 C.

Examples 18-25. In accordance with the procedures of Examples 1-17, the following compounds are prepared:

18. 3-cyclohexyl-6- (2-chlorophenyl) -1,2-dihydro-1 (or 2) -methyl-1,2,4,5-tetrazine, m.p. 130-132 ° C;

19. H-cyclohexyl-6- (2-chlorofensh1) - -1,2,4,5-tetrazine, m.p. 90-91 C;

, 20. 3- (2-iodophenyl) -6- (2-chlorophenyl) -1 (or 2) -methyl-1,2-dihydro-1, 2, -4,5-tetrazine, m.p. . 153 С;

21.3- (2-iodophenyl) -6- (2-chlorophenyl) -1,2,4,5-tetrazine, m.p. 145 C;

22.3-cyclohexyl-6- (2-bromophenyl) -1,2,2-dihydro-1 (or 2) -metx1-1,2,4,5-tetrazine, m.p. 08 C;

23.Z-cyclohexyl-6- (2-bromophenyl) -1, 2,4,5-tetrazine, m.p. 89-91 ° C;

24. 3-cyclohexyl-6- (2-fluorophenyl) -1,2-dihydro-1 (or 2) methyl-1,2,4,5-tetrazine. m.p.

25.Z-cyclohexyl-6- (2-fluorophenyl) -1, 2,4,5-tetrazine, m.p. 53-56 ° C.

The tetrazines of formula (I) are used as acaricides and / or ovicides to combat eggs and tick larvae, especially the red spider mite. Tetran-ychus cinnabarinus, as well as against the eggs and larvae of other species of mites, for example, Tetranychus urtiae, Panonychus ulmi, Phyclocoptrasta oleivora, butetranychus banksi, Panonychus citri and Tetranychus medan.

They are used in compounded formulations, which are prepared as formulations containing 0.5-99 (usually 10- 5gO)% by weight of the active substances, if necessary, the compositions are diluted before application to the treated area so that the concentration of the active ingredient in the composition was 0.05-5 wt.%.

Substituted Tetrazines of formula (I) are usually insoluble in water and can be incorporated into compositions by any of the methods adopted for insoluble substances. They can be dissolved in a water-immiscible solvent, such as a high-boiling hydrocarbon (e.g., xylene), as a carrier containing dissolved emulsifying agents, so that the composition behaves as a self-emulsifying oil when water is added.

Substituted tetrazines can, for example, be mixed with a moisturizing agent and with or without a solid carrier to form a wettable powder 5 dissolved or dispersed in water, or it can be mixed with a solid carrier to form a solid.

The aqueous suspension concentrate can be obtained by rubbing compounds with water, a wetting agent, and a suspending agent (for example, xanthan gum),

Nonionic, anionic or cationic surfactants can be used as surfactants.

Preferred surface-active agents include ethoxylated fatty alcohol sulfates, j lignin sulfonates, alkyl arylics; silat

A compound of the formula (J can be applied in any case by the presence of tick-borne infection by their eggs or larvae, or in the case of the possibility of infection on plants, animals or soil.

Plants that can be processed include agricultural and ornamental crops, such as cotton, tobacco, rice, fruit trees, and cereals, such as blocks, pears, apricots, wheat, barley, beans, sugar beet, potatoes, carrots, or greenhouse plants, such as peppers, tomatoes, cucumbers, melons, or strawberries.

For different cases, the compounds of formula (.1) can be used in different amounts. So, for example, when treating plants for inhibiting,; - yi and the amount of pests on plants, the substances are used in an amount of about 0.25-16 ounces per acre (1120 g / ha) or in a concentration from 1 to 2000 ppm. respectively, 5 preferably from 100 to 1000 m, dn or O ,, 5-ounces per acre (35-280 g / ha). Usually, the compounds are applied to the leaves of the plant; however, systematic

,

s

0

0

Chesha activity when applied to the soil around the plant roots.

Although the compounds of formula (1) are precursors of common acaricides used to combat a wide variety of diseases, they are selective, they are selective for various types of ticks. So 5 it was found that these compounds in general and 3 5 6 -bis (, 2-chlorophenyl) -1 S 2- -dihydro-methyl-1,2; 4,5-tetrazine infect mites fed on plants: effective against predatory mites.

In addition to the activity of protic acaricides, the compounds of formula (1) are also active against aphids. The growth of aphid specimens Aphis fabae (pusca), Megoura viciae (tl wiki), Sitobion avenae (grains of tl) and Myxus persicae (peach tl) is held back especially well,

Preparation of anti pest formulations

EXAMPLE 26 S The powder composition of the compound according to 1; Example 1 is prepared from the following compounds, by weight,%; Connection: from

example - 50 45 L (ligninj based on wetting agent for dispersing agent) 5

Polyfon H (sulphonated Kraft Ignin sodium salt) 2

Neosyl (precipitated silica) 10 Chinese Clay 33 Similar compositions are also prepared using as the active ingredient the compounds of Examples 13 and 16,

Example 27 The 50% wettable powder of each of the compounds of examples 1, 13 and 16 is prepared from the following ingredients jBec,%; Compounds from

examples50

Reax 45 L5

Chinese clay45

Example 28 Compositions analogous to those described in examples 26.27 are prepared with the content of each of the compounds of examples 1 to 1 7 in concentration; x 0.5; five; iO; 20; 50 and

85% by weight with appropriate variations of carrier and surfactant used in these formulations. Various carriers are used, including sand, talc, mica and solid fertilizers, various surface active agents, lignin sulfonates, alkyl-aryl sulfonates, salts. sulfonated naphthalene-formaldehyde condensates, sodium N-methyl otaate, dialkyl sulfosuccinates, alkyl phenol ethoxylates and fatty alcohol ethoxylates.

Example 29 Water-suspended concentrated formulations are prepared with the content of each of the compounds of examples 1-17 in an amount of 10, 20 and 50 weight,% by rubbing the compounds with water, xanthan gum (0.2-3% by weight of the composition) and surface active agents mentioned in Example 26 (5% by weight of the composition). The formulation is easily diluted with water to a content of the active ingredient in the range of 0.05-5 wt.%, Suitable for use.

Example 30: Emulsifiable concentrated formulations are prepared with 5, 10, 1 and 20 wt.% Each of the compounds of Examples 1-23 by dissolving the required amount of the starting compound in xylene as a carrier along with surface active agents. specified in example 26 (with a content of 1.2 or 5% by weight of the composition). The composition is readily dispersible in water to an active ingredient content of 0.05-5% by weight, suitable for use.

PRI me R A. Compositions, including water-acetone solutions containing 1000, 300, 100, 10 and 3 ppm respectively, each of these compounds together with 500 ppm wet The Lissapol NX agent (nonylphenol and ethylene oxide condensate) is used on 2 cm disc sections of leaves of a French legume plant phaseolus vulgaris infected with 50-100 eggs of a greenhouse red clove spider Tetranychus telarius. The treated leaf discs and mite eggs, together with control leaves treated with only wetting agents, are kept for 5 days at 25 ° C on wet filter paper. The percentage of mortality of its mites ticks is then calculated and op

LCjQ concentration is determined. Depending on the concentration of the drug indicate its value in the scale of 0-6:

W

15

p-20

th

25

thirty

35

40

SS1z

Cyhexatin

(CX) s SnOH

55

Amitraz5

CHjH-K CH-N-) -CI1 CH3 CH 3 CH 3

Additional tests are performed under conditions of example A, but on other types of ticks.

13

Dikofol Amitrae

Control leaf discs in water-treated and CMaMHBareniHN agent showed a mortality rate of less than 5% over the same period.

Claims (1)

Example B: French bean plants with two fully-dissolved seedlings are sprayed with water-acetone solutions of the compounds of Examples 1-13, respectively, with the ends of the active ingredient at 1000 m, d by weight per volume of solution and 500. Lissa-pol NX. After 24 hours and beyond; every seven days, up to 35 days, 2 cm discs are cut from the treated leaves, placed on wet fixing paper, and each is infected with 10 Zzeolo female Titera nychus cinnabarinus mites. After 26 hours, the ticks were removed, during which time they laid about 00 eggs on each dis. Mortality among these eggs was measured on day 6. On examination, it was found that on each disk the mortality rate is more than 95%. Formula invented The method of obtaining substituted tetrazine General formula 1 Editor S.Pekar Compiled by And ,, Korsakov Tehred At Kravchuk Proofreader A.Ilyin Order 292/60 Circulation 372 VNIIPI USSR State Committee for inventions and discoveries 113035, Moscow, Zh-ZB, Raushsk nab; d., 4/5 Polygraphic production,  N.-1 ;; Rrf y - I I ya r where R and R, which may be the same and P. are different, are hydrogen, an alkyl residue, contain 1 to 3 carbon atoms, or R, and R together is a simple bond; R is a cyclohexyl group or phenyl, substituted by one halogen atom or lower alkyl; R is a phenyl group, substituted in the second position by halogen, characterized in that the hydrazine of the general formula: II R, -NH-NH-R where R 7 is the indicated value, it is reacted with a substituted azin of the general formula III. , 25 Nz- | Ь1-1М () - С1 С1 where R and R /, have the indicated values at 30-100 ° C in an organic solvent medium followed by, if necessary, treating 15.2-dihydrotetrazine of general formula I with an oxidizing agent such as sodium nitrate, nitric acid, bromine, water peroxide - prey, in the environment of inert organic solvent, such as ice on acetic acid, carbon tetrachloride: ethanol. Subscription Uzhgorod, st. Project, 4