Benzyl-pyrimidinylalkyl-ethers as plant growth regulators and fungicides, and corresponding pyrimidinyl-carbinols

Abstract

A benzyl-pyrimidinylalkyl-ether of the formula ##STR1## in which R is alkyl, optionally substituted cycloalkyl or optionally substituted phenyl, and

X¹, X² and X³ each independently is hydrogen, halogen, alkyl, cycloalkyl, alkoxy, alkylthio, halogenoalkyl, halogenoalkoxy, halogenoalkylthio, cyano, optionally substituted phenoxy, optionally substituted phenylalkyl or optionally substituted phenylalkoxy,

or an acid addition salt or metal salt complex thereof, which possesses fungicidal and plant growth-regulating properties. The corresponding pyrimidinyl-carbinols are also new.

Description

The present invention relates to certain new benzylpyrimidinylalkyl-ethers, to a process for their preparation and to their use as plant growth regulators and fungicides. The invention also relates to certain new pyrimidinylcarbinols which are used as intermediate products for the preparation of benzyl-pyrimidinylalkyl-ethers, and to a process for the preparation of the pyrimidinylcarbinols.

It has already been disclosed that hydroxypyrimidine derivatives, for example 2-chlorophenyl-4-fluorophenyl-pyrimidin-5-yl-methanol or 4-fluorophenyl-phenylpyrimidin-5-yl-methanol, have good pesticidal properties (see U.S. Pat. Nos. 3,818,009, 3,868,244, 3,869,456 and 3,887,708).

It has already been disclosed, in addition, that 3-substituted pyridine derivatives, for example 1-(2,4-dichlorophenoxy)-2-phenyl-1-pyridin-3-yl-1-(4-chloro-2-methoxypheno xy)-2-1-pyridin-2-ethanone or 3-yl-ethanone, have good fungicidal properties (see DE-OS (German Published Specification) No. 2,909,287). However, the action of all these compounds, particularly when small quantities and low concentrations are used, is not always completely satisfactory.

The present invention now provides, as new compounds, the benzyl-pyrimidinylalkyl-ethers of the general formula ##STR2## in which R represents alkyl, optionally substituted cycloalkyl or optionally substituted phenyl and

X¹, X² and X³ are selected independently and each represent hydrogen, halogen, alkyl, cycloalkyl, alkoxy, alkylthio, halogenalkyl, halogenoalkoxy, halogenoalkylthio, cyano, optionally substituted phenyl, optionally substituted phenoxy, optionally substituted phenylalkyl or optionally substituted phenyalkoxy,

and the acid-addition salts and metal-salt complexes thereof.

The compounds of the formula (I) have an asymmetric carbon atom; they can therefore occur as the two optical isomers or as the racemate. All of the isomers are comprehended by formula (I)

The present invention also provides a process for the preparation of a benzyl-pyrimidinylalkyl-ether of the formula (I), or an acid addition salt or metal salt complex thereof, in which a pyrimidinyl-carbinol of the general formula ##STR3## in which R has the meaning given above, is reacted with a benzyl halide of the general formula ##STR4## in which X¹, X² and X³ have the meanings given above and Hal represents halogen,

in the presence of a solvent and, if appropriate, in the presence of a strong base or, if appropriate, in the presence of an acid-binding agent, and, if required, an acid or a metal salt is added onto the resultant compound.

It has been found that the benzyl-pyrimidinyl-alkyl-ethers of the formula (I) and the acid addition salts and metal salt complexes thereof have powerful plant growth-regulating and fungicidal properties.

Surprisingly, the compounds of the formula (I) according to the invention show a better growth-regulating action than the known hydroxypyrimidine derivatives from the state of the art, and a better fungicidal action than the 3-substituted pyridine derivatives which are likewise known. The active compounds according to the invention thus represent an enrichment of the art.

Formula (I) gives a general definition of the benzyl-pyrimidinylalkyl-ethers according to the invention.

Preferably, in this formula,

R represents straight-chain or branched alkyl having 1 to 8 carbon atoms; cycloalkyl which has 3 to 7 carbon atoms and which is optionally substituted by alkyl having 1 to 4 carbon atoms; or optionally substituted phenyl, preferred substituents being halogen, alkyl and alkoxy, each having 1 to 4 carbon atoms, and halogenoalkyl having 1 to 2 carbon atoms and 1 to 5 identical or different halogen atoms (especially fluorine atoms and chlorine atoms),

X¹ represents hydrogen, halogen, straight-chain or branched alkyl having 1 to 4 carbon atoms, cycloalkyl having 3 to 7 carbon atoms, alkoxy or alkylthio, each having 1 to 4 carbon atoms, halogenoalkyl, halogenoalkoxy or halogenoalkylthio, each having 1 to 4 carbon atoms and 1 to 5 identical or different halogen atoms (especially fluorine atoms and chlorine atoms), cyano or optionally substituted phenyl, phenoxy, phenylalkyl having 1 to 4 carbon atoms in the alkyl part or phenylalkoxy having 1 to 4 carbon atoms in the alkoxy part, preferred substituents in each case being halogen and/or alkyl having 1 to 4 carbon atoms,

X² represents hydrogen, halogen, straight-chain or branched alkyl having 1 to 4 inventina as such, in the form of their formulations or as the use forms prepared therefrom, such as ready-to-use solutions, emulsifiable concentrates, emulsions, foams, suspensions, wettable powders, pastes, soluble powders, dusting agents and granules. They may be used in the customary manner, for example by watering, spraying, atomising, scattering, dusting, foaming, coating and the like. Furthermore, it is possible to apply the active compounds in accordance with the ultra-low volume process or to inject the active compound preparation or the active compound itself into the soil. It is also possible to treat the seeds of plants.

When the compounds according to the invention are employed as plant growth regulators, the use quantities can be varied within a relatively wide range. In general 0.01 to 50 kg. preferably 0.05 to 10 kg, are used per hectare of soil area.

According to the type of application, the use quantity can be varied within a relatively wide range also when the substances according to the invention are employed as fungicides. Thus, especially in the treatment of parts of plants, the active compound concentrations in the use forms are, in general, between 1 and 0.0001% by weight, preferably between 0.5 and 0.001% by weight. For the treatment of seeds, quantities of active compound of generally 0.001 to 50 g, preferably 0.01 to 10 g, are employed per kg of seed. For the treatment of soil, active compound concentrations, at the point of action, of generally 0.00001 to 0.1% by weight, preferably of 0.0001 to 0.02%, are employed.

The present invention also provides a plant growth regulating or fungicidal composition containing as active ingredient a compound of the present invention in admixture with a solid or liquefied gaseous diluent or carrier or in admixture with a liquid diluent or carrier containing a surface-active agent. The present invention also provides a method of combating fungi which comprises applying to the fungi, or to a habitat thereof, a compound of the present invention alone or in the form of a composition containing as active ingredient a compound of the present invention in admixture with a diluent or carrier.

The present invention also provides a method of regulating the growth of plants which comprises applying to the plants, or to a habitat thereof, a compound of the present invention alone or in the form of a composition containing as active ingredient a compound of the present invention in admixture with a diluent or carrier.

The present invention further provides crops protected from damage by fungi by being grown in areas in which immediately prior to and/or during the time of the growing a compound of the present invention was applied alone or in admixture with a diluent or carrier.

The present invention further provides plants, the growth of which has been regulated by their being grown in areas in which immediately prior to and/or during the time of the growing a compound of the present invention was applied alone or in admixture with a diluent or carrier.

It will be seen that the usual methods of providing a harvested crop may be improved by the present invention.

PREPARATIVE EXAMPLES

PAC Example 1

Preparation of the starting material ##STR24##

225 g of 5-bromopyrimidine were dissolved in 1.5 liters of absolute tetrahydrofuran/1,000 ml of absolute ether, and the solution was cooled to -120°C 250 ml of 50% strength n-butyl-lithium (in n-hexane) were added dropwise to the solution, during the course of 2 hours, at an internal temperature of -105° to -115°C The mixture was further stirred for 1 hours at this temperature. 309 ml of trimethylacetaldehyde was then added dropwise during the course of 2 hours. The reaction mixture was then further stirred for 4 hours at this temperature. The reaction mixture was allowed to warm up to room temperature overnight, and 83 g of ammonium chloride, dissolved in a minimum quantity of water, were then added to it. The aqueous phase was separated off, and the organic phase was washed twice with saturated aqueous sodium chloride solution, dried over sodium sulphate and concentrated. 155 g (56% of theory) of 5-(1-hydroxy-2,2-dimethylpropyl)pyrimidine of melting point 94°-96°C were obtained after recrystallization of the residue from acetonitrile.

The following starting materials of the formula (II) were obtained by analogous methods:

TABLE 2
______________________________________
##STR25##                    (II)
Starting
Material
No.        R            Physical constants
______________________________________
II-2       CH(CH3)2
boiling point:
80-82°C/0.02 mm Hg
II-3
##STR26##   melting point: 85-87°C
II-4
##STR27##
II-5       (CH2)4 CH3
boiling point:
118-25°C/0.005 mbar
______________________________________
##STR28##                     (1)
##STR29##                     (1)

200 ml of 33% strength aqueous sodium hydroxide solution were added to a solution of 16.6 g of 5-(1-hydroxy-2,2-dimethylpropyl)-pyrimidine, 32.2 g of 4-chlorobenzyl chloride and 6 g of tetrabutylammonium bromide in 200 ml of toluene. The reaction mixture was stirred vigorously at room temperature for 18 hours.

The aqueous phase was separated off, and the toluene phase was diluted with toluene, washed four times with water and once with saturated aqueous sodium chloride solution, dried over sodium sulphate and concentrated. The oleaginous residue was dissolved in ether/hexane, and the solution was treated with hydrogen chloride gas. The resulting crystalline precipitate was filtered off under suction and rinsed with ether, and ethyl acetate/1N sodium hydroxide solution was added to it, the free base again being formed.

20.3 g (70% of theory) of 5-[1-(4-chlorobenzyloxy)-2,2-dimethylpropyl]-pyrimidine of melting point 77°-78.5°C were obtained after recrystallization from hexane. ##STR30##

3.3 g of sodium hydride (80% strength in paraffin oil) were added to a solution of 16.6 of 5-(1-hydroxy-2,2-dimethylpropyl)-pyrimidine in 150 ml of absolute dimethylsulphoxide, while stirring at room temperature. After 1 hour, a solution of 17.3 g of 4-methoxybenzyl chloride in 50 of absolute dimethylsulphoxide was added dropwise to the mixture. The reaction mixture was then further stirred for 3 days at room temperature.

The dimethylsulphoxide solution was concentrated, and the residue was taken up in ethyl acetate, washed once with water and once with saturated aqueous sodium chloride solution, dried over sodium sulphate and concentrated. The residue was dissolved in ether/hexane and the solution was treated with hydrogen chloride gas. The resulting crystalline precipitate was filtered off under suction and rinsed with ether, and ethyl acetate/1N 1N sodium hydroxide solution was added to it, the free base being formed. 25.4 g (89% of theory) of 5-[1-(4-methoxybenzyloxy)-2,2-dimethylpropyl]-pyrimidine were obtained as a pale yellow oil with a reractive index n_D²0 : 1.5388.

The following compounds of the general formula (I) were obtained in a corresponding manner:

TABLE 3
______________________________________
##STR31##                     (I)
Com-                               Melting point (°C.)
pound                              or refractive index
No.   X1  X2
X3
R        (nD20)
______________________________________
3     2-Cl     6-F    H   C(CH3)3
63-64
4     4-CH3
H      H   C(CH3)3
39-44
5     4-F      H      H   C(CH3)3
1,5230
6     2-Cl     4-Cl   H   C(CH3)3
59-61
7     3-Cl     4-Cl   H   C(CH3)3
63-66
##STR32##
H      H   C(CH3)3
95-97
9     4-Cl     H      H   CH(CH3)2
1.5478
10    4-F      H      H   CH(CH3)2
1.5242
11    4-CF3
H      H   C(CH3 )3
1.4986
12    4-OCF3
H      H   C(CH3)3
1.4949
13    4-OCH3
H      H
##STR33##
1.5511
14    4-Cl     H      H
##STR34##
1.5602
15    4-F      H      H
##STR35##
1.5391
16    3-Cl     4-Cl   H
##STR36##
1.5622
17    2-Cl     4-Cl   H
##STR37##
1.5687
18    H        H      H   C(CH3)3
1.5345
19    4-Cl     H      H   C(CH3)3
140-142
(× HCl)
20    4-OCH3
H      H   (CH2)4 CH3
1.5320
21    4-Cl     H      H   (CH2)4 CH3
1.5348
22    2-Cl     4-Cl   H   (CH2)4 CH3
1.5459
23    3-Cl     4-Cl   H   (CH2)4 CH3
1.5402
24    4-F      H      H   (CH2)4 CH3
1.5155
25    2-Cl     4-Cl   H   CH(CH3)2
1.5592
______________________________________

USE EXAMPLES

The plant-growth regulating and fungicidal activity of the compounds of this invention is illustrated by the following examples wherein the compounds according to the present invention are each identified by the number (given in brackets) from the preparative examples and Table 3 hereinabove.

The known comparison compounds are identified as follows: ##STR38##

EXAMPLE 3

PAC Inhibition of growth of grass (Festuca pratensis)

Solvent: 30 parts by weight of dimethylformamide.

Emulsifier: 1 part by weight of polyoxyethylene sorbitan monolaurate.

To produce a suitable preparation of active compound, 1 part by weight of active compound was mixed with the stated amounts of solvent and emulsifier and the mixture was made up to the desired concentration with water.

Grass (Festuca pratensis) was grown in a greenhouse up to a height in growth of 5 cm. In this stage, the plants were sprayed with the preparations of active compound until dripping wet. After 3 weeks, the additional growth was measured and the inhibition of growth in percent of the additional growth of the control plants was calculated. 100% inhibition of growth meant that growth had stopped and 0% denoted a growth corresponding to that of the control plants.

In this test, the compounds (1), (5), (6), (7) (9) and (10) showed a better inhibition of growth than the compounds (A) and (B) known from the state of the art.

EXAMPLE 4

PAC Inhibition of growth of barley

Solvent: 30 parts by weight of dimethylformamide.

Emulsifier: 1 part by weight of polyoxyethylene sorbitan monoalaurate.

To produce a suitable preparation of active compound, 1 part by weight of active compound was mixed with the stated amounts of solvent and emulsifier and the mixture was made up to the desired concentration with water.

Barley plants were grown in a greenhouse to the 2-leaf stage. In this stage, the plants were sprayed with the preparations of active compound until dripping wet. After 3 weeks the additional growth was measured on all of the plants and the inhibition of growth in percent of the additional growth of the control plants was calculated. 100% inhibition of growth meant that growth had stopped and 0% denoted a growth corresponding to that of the control plants.

In this test, the compounds (6), (18), (9) and (10) showed a better inhibition of growth than the compounds (A) and (B) known from the state of the art.

EXAMPLE 5

PAC Inhibition of growth of cotton

Solvent: 30 parts by weight of dimethylformamide.

Emulsifier: 1 part by weight of polyoxyethylene sorbitan monolaurate.

To produce a suitable preparation of active compound, 1 part by weight of active compound was mixed with the stated amounts of solvent and emulsifier and the mixture was made up to the desired concentration with water.

Cotton plants were grown in a greenhouse until the 5th secondary leaf had unfolded completely. In this stage, the plants were sprayed with the preparations of active compound until dripping wet. After 3 weeks, the additional growth in percent of the additional growth of the control plants was calculated. 100% inhibition of growth means that growth had stopped and 0% denoted a growth corresponding to that of the control plants.

In this test, the compounds (1), 3), (5), (6), (7), (8), (14), (15), (17), (9) and (10) showed a better inhibition of growth than the compound (A) known from the state of the art.

EXAMPLE 6

PAC Inhibition of growth of soybeans

Solvent: 10 parts by weight of methanol.

Emulsifier: 2 parts by weight of polyoxyethylene sorbitan monolaurate.

To produce a suitable preparation of active compound, 1 part by weight of active compound was mixed with the stated amounts of solvent and emulsifier and the mixture was made up to the desired concentration with water.

Young soybean plants, in the stage at which the first secondary leaves had unfolded, were sprayed with the preparations of active compound until dripping wet. After 2 weeks, the additional growth was measured and the inhibition of growth in % of the additional growth of the control plants was calculated. 100% meant that growth had stopped and 0% denoted a growth corresponding to that of the control plants.

In this test, the compounds (1), (3), (4), (5), (6), (7), (14), (12), (11), (17), (18), (9), (10) and (2) showed a better inhibition of growth than the compound (A) known from the state of the art.

EXAMPLE 7

PAC Inhibition of growth of sugar beet

Solvent: 30 parts by weight of dimethylformamide.

Emulsifier: 1 part by weight of polyoxyethylene sorbitan monolaurate.

To produce a suitable preparation of active compound, 1 part by weight of active compound was mixed with the stated amounts of solvent and emulsifier and the mixture was made up to the desired concentration with water.

Sugar beet was grown in a greenhouse until formation of the cotyledons was complete. In this stage, the plants were sprayed with the preparation of active compound until dripping wet. After 14 days, the additional growth of the plants was measured and the inhibition of growth in percent of the additional growth of the control plants as was calculated. 0% inhibition of growth denoted a growth which corresponded to that of the control plants. 100% inhibition of growth meant that growth had stopped.

In this test, the compounds (1), (3), (4), (5), (6), (7), (14), (12), (11), (17), (13), (18), (9), (10), (2) and (8) showed a better inhibition of growth than the compounds (A) and (B) known from the state of the art.

EXAMPLE 8

PAC Erysiphe test (barley)/protective/

Solvent: 100 parts by weight of dimethylformamide.

Emulsifier: 0.25 part by weight of alkyl aryl polyglycol ether.

To produce a suitable preparaton of active compound, 1 part by weight of active compound was mixed with the stated amounts of solvent and emulsifier, and the concentrate was diluted with water to the desired concentration.

To test for protective activity, young plants were sprayed with the preparation of active compound until dew-moist. After the spray coating had dried on, the plants were dusted with spores of Erysiphe graminis f.sp. hordei.

The plants were placed in a greenhouse at a temperature of about 20° C. and a relative atmospheric humidity of about 80%, in order to promote the development of powdery mildew pustules.

Evaluation was carried out 7 days after the inoculation.

In this test, a significant superiority in activity, compared with the compounds (C) and (D) known from the state of the art, was shown, for example, by the compounds (1), (3), (4), (5), (6), (7) and (8).

EXAMPLE 9

PAC Increase of the photosynthesis in soybeans

It has been found that the compounds (14) and (16) cause a significant increase of photosynthesis in soybeans.

It will be appreciated that the instant specification and examples are set forth by way of illustration and not limitation, and that various modifications and changes may be made without departing from the spirit and scope of the present invention.

Claims

1. A benzyl-pyrimidinylalkyl-ether of the formula ##STR39## in which R is alkyl having 1 to 8 carbon atoms; cycloalkyl which has 3 to 7 carbon atoms and which is optionally substituted by alkyl having 1 to 4 carbon atoms; or phenyl which is optionally substituted by halogen, alkyl having 1 to 4 carbon atoms, alkoxy having 1 to 4 carbon atoms and/or halogenoalkyl having 1 to or 2 carbon atoms and 1 to 5 halogen atoms, having 1 to 2 carbon atoms and 1 to 5 halogen atoms,

X¹ is hydrogen, halogen, alkyl having 1 to 4 carbon atoms, cycloalkyl having 3 to 7 carbon atoms, alkoxy having 1 to 4 carbon atoms, alkylthio having 1 to 4 carbon atoms, halogenoalkyl having 1 to 4 carbon atoms and 1 to 5 halogen atoms, halogenoalkoxy having 1 to 4 carbon atoms and 1 to 5 halogen atoms, halogenoalkylthio having 1 to 4 carbon atoms and 1 to 5 halogen atoms, phenyl which is optionally sustituted by halogen and/or by alkyl having 1 to 4 carbon atoms, phenoxy which is optionally substituted by halogen and/or by alkyl having 1 to 4 carbon atoms, phenylalkyl which has 1 to 4 carbon atoms in the alkyl part and which is optionally substituted in the phenyl part by halogen and/or by alkyl having 1 to 4 carbon atoms, or phenylalkoxy which has 1 to 4 carbon atoms in the alkoxy part and which is optionally substituted in the phenyl part by halogen and/or by alkyl having 1 to 4 carbon atoms, and

X² and X³ each independently is hydrogen, halogen, alkyl having 1 to 4 carbon atoms, cycloalkyl having 3 to 7 carbon atoms, alkoxy having 1 to 4 carbon atoms, alkylthio having 1 to 4 carbon atoms or halogenoalkyl, halogenoalkoxy or halogenoalkylthio each having 1 to 4 carbon atoms and 1 to 5 halogen atoms,

or an acid addition salt or metal salt complex thereof.

2. A compound according to claim 1, in which

R is alkyl with 1 to 8 carbon atoms, cycloalkyl with 3 to 7 carbon atoms or phenyl,

X¹ is hydrogen, halogen, alkyl with 1 to 4 carbon atoms, alkoxy with 1 to 4 carbon atoms, halogenoalkyl with 1 to 4 carbon atoms and 1 to 5 halogen atoms, halogenoalkoxy with 1 to 4 carbon atoms and 1 to 5 halogen atoms or phenyl,

X² is hydrogen or halogen, and

X³ is hydrogen

or a hydrochloric acid addition salt thereof.

3. A compound according to claim 1 in which

R is isopropyl, isobutyl, tert.-butyl, n-pentyl, n-hexyl, optionally methyl-substituted cyclopentyl or cyclohexyl, or phenyl which is optionally substituted by fluorine, chlorine, methyl, methoxy or trifluoromethyl,

X¹ is hydrogen, fluorine, chlorine, methyl, tert.-butyl, cyclohexyl, methoxy, methylthio, trifluoromethyl, trifluoromethoxy, trifluoromethylthio, cyano, or phenyl, phenoxy, benzyl or benzyloxy, each of which is optionally substituted by fluorine, chlorine or methyl,

X² is hydrogen, fluorine, chlorine, methyl, tert.-butyl, cyclohexyl, methoxy, methylthio, trifluoromethyl, trifluoromethoxy or trifluoromethylthio, and

X³ is hydrogen, fluorine, chlorine, methyl, methoxy, methyl or trifluoromethyl,

or an addition salt thereof with a hydrohalic acid, phosphoric acid, nitric acid, sulphuric acid, a sulphonic acid or a monofunctional or bifunctional carboxylic or hydroxycarboxylic acid, or a complex thereof with a salt, the metal of the salt being copper, zinc, manganese, magnesium, tin, iron or nickel and the anion of the salt being halide, phosphate or sulphate.

4. A compound according to claim 1, wherein such compound is 5-[1-(4-chlorobenzyloxy)-2,2-dimethylpropyl]-pyrimidine of the formula ##STR40##

5. A compound according to claim 1, wherein such compound is 5-[1-(4-methoxybenzyloxy)-2,2-dimethylpropyl]-pyrimidine of the formula ##STR41##

6. A compound according to claim 1, wherein such compound is 5-[1-(2-chloro-6-fluorobenzyloxy)-2,2-dimethylpropyl]-pyrimidine of the formula ##STR42##

7. A compound according to claim 1, wherein such compound is 5-[1-(4-fluorobenzyloxy)-2,2-dimethylpropyl]-pyrimidine of the formula ##STR43##

8. A compound according to claim 1, wherein such compound is 5-[1-(2,4-dichlorobenzyloxy)-2,2-dimethylpropyl]-pyrimidine of the formula ##STR44##

9. A compound of the formula ##STR45## wherein R is benzyl; benzyl substituted on the aryl ring with 1 to 3 of the same or different halo, lower alkoxy, lower alkyl, or lower alkyl substituted with 1 to 5 of the same or different halogens; phenylbenzyl; or phenylbenzyl substituted in the benzene rings with halo or lower alkyl;

R¹ is alkyl having 1 to 8 carbon atoms, phenyl or phenyl substituted with substituents selected from halo, C₁-4 -alkoxy or C₁-2 -alkyl substituted with the same or different halogens.

10. A compound of the formula described in claim 9 wherein R¹ is phenyl or phenyl substituted with substituents selected from halo, C₁-4 -alkoxy or C₁-2 -alkyl substituted with the same or different halogens. 11. A compound of the formula described in claim 10 werein R is benzyl or benzyl substituted on the aromatic ring with 1 to 5 of the same or different substituents selected from halo, lower alkoxy, lower alkyl or lower alkyl substituted with 1 to

5 of the same or different halogens. 12. A compound of the formula described in claim 10 wherein R¹ is chlorophenyl. 13. A compound of the formula described in claim 12 wherein R is 2,4-dichlorobenzyl. 14. A compound of the formula described in claim 12 wherein R is trifluoromethylbenzyl.