DE2246645C3 - 2-Amino-4-hydroxypyrimidine sulfamic acid ester - Google Patents

Description

N N

R ₁ R ₂

in which the radicals Ri to R4 are mentioned in claim 1 Have meaning with a sulfamic acid chloride of the general formula IU

Cl-SO ₂ -N

(III)

in which the radicals R5 and Ri, which in claim 1 have the meaning mentioned, implemented in a manner known per se.

5. Fungicidal agent, consisting of a compound according to claim 1 and customary auxiliary and Carriers.

British patent specification 11 85 039 describes pyrimine derivatives of the formula:

or salts of such derivatives, where in the formula Ri and R2 denotes hydrogen atoms or substituted or unsubstituted hydrocarbon groups, or together with the adjacent N atom form a heterocyclic ring, which one or more may contain additional heteroatoms; R) and R4 Hydrogen or halogen atoms, substituted or unsubstituted hydrocarbon groups or nitro groups mean; X is an oxygen or sulfur atom; and R5 is a carbonyl or sulfonyl group, which directly or via an oxygen or sulfur atom is a substituted or unsubstituted hydrocarbon group or carries a heterocyclic group. These compounds are useful as fungicides.

In the above British patent specification 85 039 there are therefore certain sulfonyl ester derivatives of pyrimidines disclosed. However, only one sulfamyl ester is specified in this patent, which is the Structure:

FI

55

N N

N (CH ₃ J ₂

OSO, · N

owns. It is true that these compounds have fungicidal activity against individual pests. You own however, no broad spectrum activity and often only act against individual pests Application in a relatively high concentration.

In British Patent 11 82 584 are fungicidal effective pyrimidine derivatives described which a

fts 6-hydroxy group (or a 6-metcaptoe: r group) and a 2-amino group on the pyrimidine ring. These pyrimidine derivatives are highly active fungicides.
None of the connections which in either of the two

aforementioned British patents are specifically disclosed, but has a high level of activity against all types of powdery mildew and especially against powdery powdery mildew of apples, Podosphaera leucotricha.

It has now been found that certain 2-amino-4-hydroxypyrimidine-sulfamic acid esters are fungicides with a particularly broad spectrum and have a higher degree of effectiveness against powdery types of mildew, in particular against powdery mildew
Apple trees, Podosphaera leucotricha.

The invention therefore relates to 2-amino-4-hydroxypyrimidine sulfamic acid esters of the general formula I.

NR ¹ R ²

Ethyl radical or together with the neighboring nitrogen atom mean a pyrrolidine ring.

A particularly preferred and highly effective compound is 2-ethylamino-4-hydΓOxy-5-butyl-6-methyl-pyrirnidine-N.N-dimethyl-sulfamic acid ester.

The 2-amino-4-hydroxypyrimidine sulfamic acid esters according to the invention are prepared by using a 4-hydroxypyrimidine of the general form! II

from ίο

(II)

in which the radicals Ri to R4 are mentioned in claim 1 Have meaning with a sulfamic acid chloride of the general formula III

in which either R ^{1 is} a hydrogen atom or a lower alkyl radical and R ^{2 is} a lower alkyl or allyl radical or R ¹ and R ² together with the nitrogen atom attached to these groups are a pyrrolidine ring, R ^{J is} a lower alkyl radical, R ^{4 is} a butyl , Allyl or propargyl radical and either R5 ■ and Re, independently of one another, each represent a lower alkyl or allyl radical or R ⁵ and R ⁶ together with the nitrogen atom bonded to these groups represent a pyrrolidine, morpholine or N-methylpiperazine ring.

Preferred pyrimidinesulfamic esters are those in which R ¹ and R ^{2 have} the meaning given above and R ^{J is} a methyl radical, R ^{4 is} a butyl radical and either R ⁵ and R ^{6 are} methyl or Cl-SO ₂ -N

(III)

in which the radicals R5 and Rö are mentioned in claim 1 Have meaning, implemented in a manner known per se.

Specific pyrimidine derivatives of the invention which have been found to be particularly useful are listed in Table 1 below. The positions of the radicals Ri to Re mentioned in this table result from the general formula I.

Table I. Compound R ¹ R ²

R ⁵

Melting point

CHj CHj CHj "C ₄ H, CHj CHj ClI ₃ HC ₄ II, CHj CHj CHj 11C ₄ H, H C ₂ H ₅ CHj MC ₄ ed

CHj

CIIj

- N

-N O

- N

oil
Oil

Dl

72 "C

5 H CHj CHj nt ■ 4II » nt '411, - N v_ nC JU Il C ₂ H ₅ C ₂ H ₅ 6th II C ₂ II ₅ CH, mC 41 U 0 7th Il C ₂ H ₅ cn., / K JU - n ' 0 K C ₁ H ₅ C ₂ H ₅ CH, nt II. 77

continuation

Connection R '

H nC ₄ H "

- Ν

CH, IfC ₄ H,

CH .. BC ₄ H,

CH, nC ₄ H,

- Ν

- ■ / Ί

- Ν

Melting point

56 C

60 C

88 C

12th II ISO-C ₃ H ₇ CH, nC ₄ H, --N -N CH, ^/ ISO-C ₄ H ₉ O -C ₂ H ₅ Oil 13th Ii CjH ₅ CH, IfC ₄ H, ISO-C ₄ H, CH, CH, cn, Oil 14th Il CjH ₅ CH .. IfC ₄ H, CH, -N CH, ISO-C ₁ H ₇ CH, Oil 15th H CjH, CH, rC ₄ U _v JSO-C ₁ H ₇ (H, hC, H ₇ CH, Oil 16 H CjH ₅ CH, IfC ₄ H, iiC, H ₇ -CH ₂ CH N-CH, CW ₁ CH ₂ (H- Oil 17th Ii C ₂ H ₅ CH, HC ₄ H, cn, H (Ji, Oil 18th Ii C ₂ H ₅ CH, nC ₄ H, CH, Oil 19th Ii C ₂ H ₅ CH, HC ₄ H, Sehmp. HB bib
104 C 20th H C ₂ Ii ₅ CH, HC ₄ H, Oil 21 H -CH ₂ CH = CH ₂ CH, ISO-C ₄ H, »Rc 22nd H -CH ₂ CH: CH ₂ CH, -CH ₂ C \ i: CH ₂ 82 C 23 II -CH ₂ CH = CH ₂ CH, - CH ₂ C = CH M.p. 62 to
64 C 24 H C ₂ H ₅ CH, IfC ₄ H, (H ₂ Ol 25th II C ₂ H ₅ "C ₁ II ₇ HC ₄ II, Oil

For compounds which are listed in Table I as "oils" 40: are shown, elemental analyzes were carried out. The results are as follows:

Ver Calculated H N Found Il N binding
No. C. 7.59 17.73 C. 6.96 17.82 1 49.35 7.26 15.64 49.18 7.41 15.25 3 50.30 8.14 16.28 49.95 7.97 16.11 7th 52.3 9.00 14.00 52.44 9.30 13.61 13th 57.00 7.6 17.7 56.92 7.37 17.5 14th 49.5 8.60 15.06 48.0 8.59 14.62 15th 54.80 8.60 15.06 54.94 8 60 14.5 16 54.5 8.38 15.64 55.02 8.41 15.89 18th 53.60 7.26 15.64 53.52 7.34 16.00 19th 50.30 7.88 16.98 51.10 7.69 16.70 20th 50.93 8.60 15.06 50.88 8.59 14.62 15th 54.80 7.37 17.06 54.94 7.08 16, V9 21 51.20 6.45 17.93 50.60 6.29 17.59 22nd 49.98 5.84 18.05 49.34 5.57 17.95 23 50.30 7.61 15.22 49.14 7.66 15.30 24 55.40 8.14 16.28 54.95 8.17 15.92 25th 52.3 9.00 14.00 52.55 8.91 13.57 26th 57.00 56.35

(10

Compounds of numbers 1, 2, 4, 7, 10 and 14 are particularly useful fungicides. The numbering of the pyrimidine ring is here

N 3

Il

IN

It should be noted that the 4 and 6 positions are equivalent are.

In the preparation of the compounds according to the invention, molar proportions are the reactants particularly preferred.

Examples of suitable salts of the pyrimidine derivatives according to the invention are the hydrochlorides mentioned. Other salts include the salts of the pyrimidine derivatives with organic acids, for example Acetates or picrates. These salts can easily be prepared in the usual way by adding the appropriate acid added to the pyrimidine sulfamate.

As mentioned above, the compounds of the invention are active fungicides, which are particularly are useful against the diseases:

Sphaerotheca fuliginea (powdery mildew) on cucumber
P ^ dosphaera leucotricha (powdery mildew) on apple
Uncinula necator (powdery mildew) on wine
Erysiphegraminis (powdery mildew) on barley
Erysiphe graminis (powdery mildew) on wheat

To combat fungal attack, the compounds can be used as such, but they will more conveniently formulated into mixtures for such use.

The invention therefore also relates to a fungicidal agent which consists of a pyrimidinesulfamic acid ester according to the invention and usual auxiliaries and carriers. Particularly preferred are agents as Pyrimidinesulfamic acid esters according to the invention contain a compound according to claim 2 or 3.

The active pyrimidinesulfamic acid derivatives according to the invention and the preparations according to the invention, which contain these can be used to control plant fungi in a variety of ways or to treat plants or seeds. So you can put them directly on the foliage of a plant raise which one is infected, or is likely to be infected. You can also see them on bushes or Trees, on seeds or other reproductive parts of plants or on the ground or a apply another medium in which plants, bushes or trees grow or are planted should. They can be sprayed on, dusted on or applied as a cream or paste preparation. Application can be to any part of the plant, bush or tree, for example on the foliage, stems, branches or roots. All of these types of application or application fall within the scope of the expression "treatment", as it is used here, and the word "plant" is intended to include saplings, bushes and trees include. As is further apparent from the foregoing, the invention encompasses contraceptive, protective, prophylactic and eradicating treatment.

The pyrimidine derivatives according to the invention are preferably used in the form of preparations and these preparations can be used for agricultural and horticultural purposes. The kind the preparation used in any case depends on the particular purpose for which it is used should be used.

The preparations can be in the form of dust powders or granules, with the active Component is mixed with a solid diluent or carrier. Suitable solid diluents or carriers can, for example, be kaolin, bentonite, kieselguhr, dolomite, calcium carbonate, talc, powdered Magnesia, fuller's earth, gypsum, Hewitt earth, diatomaceous earth or china clay. Mixtures or preparations for dressing seeds can for example have a means which the adhesion of the preparation supported on the seed, for example a mineral oil.

The preparations can also be in the form of dispersible ones Powders or granules are present which, in addition to the active ingredient, have a wetting agent in order to to facilitate the dispersion of the powder or grains in liquids. Such powders or grains may include fillers, suspending agents and the like.

The aqueous dispersions or emulsions can be prepared by adding the active ingredient or dissolves the constituents in an organic solvent that contains one or more wetting, Can contain dispersants or emulsifiers and then add the mixture thus obtained to water added, which contain one or more wetting, dispersing or emulsifying agents in a similar manner can. Suitable organic solvents are ethylene dichloride, isopropyl alcohol, propylene glycol, Diacetone alcohol, toluene, kerosene, methylnaphthalene, xylenes and trichlorethylene.

The mixtures that are to be used as sprays can also be in the form of aerosols, the preparation being placed in a container under pressure in the presence of a propellant such as fluorotrichloromethane or dichlorodifluoromethane is held.

By incorporating suitable additives, for example to improve the distribution, the Adhesion and the resistance to rain on treated surfaces can make the different preparations can be adapted to the different types of use.

The mixtures can also be in the form of liquid preparations, which are dipped or Jumps should be used and soft, generally aqueous dispersions or emulsions are that the active ingredient in the presence of one or more wetting agents, dispersants, emulsifiers or contain suspending agents.

Wetting agents, dispersants and emulsifiers can be cationic, anionic or nonionic. to suitable cationic agents include, for example, quaternary ammonium compounds, e.g. B. Cetyltrimethylammonium bromide. Suitable anionic agents include, for example, soaps and salts of aliphatic monoesters sulfuric acid, e.g. B. sodium lauryl sulfate, salts of sulfonated aromatic compounds, e.g. B. Sodium Dodecylbenzenesulfonate, Sodium, calcium or ammonium lignosulfonate, butyl naphthalene sulfonate, and a Mixture of the sodium salts of diisopropyl and triisopropyl naphtha sulfonic acids. To suitable Nonionic agents include, for example, the condensation products of ethylene oxide with skin alcohols such as oleyl alcohol or cetyl alcohol or with alkyl phenols such as octylphenol, nonylphenol and octyl cresol. Other nonionic agents are the partial esters, which The condensation products of these partial esters are derived from long-chain fatty acids and hexitol anhydrides with ethylene oxide and the lecithins.

Suitable suspending agents are, for example, hydrophilic colloids, e.g. B. polyvinylpyrrolidone and sodium carboxymethyl cellulose, and the vegetable gums, e.g. Gum acacia and gum tragacanth.

The preparations which are used in the form of aqueous dispersions or emulsions are usually supplied in the form of a concentrate which is high in active Contains ingredient, this concentrate must be diluted with water before use. This Concentrates are often required to withstand storage for extended periods of time and after to be capable of such storage of dilution with water to form aqueous preparations, which remain homogeneous for a sufficient time to be applied by conventional spray equipment to be able to. The concentrates can conveniently contain about 10 to 85% by weight of the active ingredient, preferably about 25 to 60% by weight of the active ingredient. Are such preparations for Formation of diluted aqueous preparations, so they can contain different amounts of the active ingredient included, depending on the purpose for which they are to be used, but generally will an aqueous preparation used, which between 0.001 and 0.01 wt .-% up to about 10 wt .-% contains active ingredient

The production of the compound according to the invention

gen is illustrated by the following working examples.

example 1

This example illustrates the preparation of S-n-butyl-1-dimethylamino-1-hydroxy-e-methyl-pyrimidinyl-1-pyrrolidine sulfonic acid ester Formula:

C ₄ H ₉ (/,)

N N

NHC ₃ H ₇ Oi)

(Compound No. 10 of Table I)

Example 4

This example illustrates the preparation of the compound of formula

N (CH ₃ ),

(Compound No. 2 of Table I)

392.1 g of 5-n-butyl-2-dimethylamino-4-hydroxy-6-methylpyrimidine are added to a solution of sodium ethylate, which was prepared by dissolving 43.3 g of sodium in 1340 cm ^{3 of ethanol.} The ethanol is then removed by distillation and replaced by dry ethyl acetate, some of which is distilled off in order to remove the last traces of ethanol. 300 g of 1-pyrrolidine sulfomyl chloride are added to the resulting mixture and the mixture is refluxed for a few hours. After cooling and filtering off the insoluble part, the filtrate is washed with 5% sodium hydroxide solution and then with water until neutral wash water is obtained. After drying over anhydrous sodium sulfate, the volatile fraction is removed by evaporation under reduced pressure, the last traces of the solvent being removed by heating to 80 ° C. under high vacuum. The remaining undistillable oil is 5-n-butyl-2-dimethylamino-4-hydroxy-6-methyl-pyrimidinyl-1-pyrrolidinesulfonic acid ester.

The compounds of numbers 3, 4, 8, 9, 10. 11, 17 and 19 are produced in an analogous manner, whereby one the appropriate respondents are used

30th

35

Example 2

In a similar experiment to that illustrated in Example 1 but using of the corresponding hydroxypyrimidine and using toluene to support the Removing the last traces of ethanol before adding the ethyl acetate, one obtains 5-n-ButyI-4-hydroxy-e-methyl ^ -n-propylamino-pyrirnidinyl-1 -pyrrolidinsulfonsäureester of the formula:

OSO ₂ -N

N N

(Compound No. 11 in Table I)

ί, 15 g of sodium are dissolved in 100 cm ^{3 of} ethanol, 11.77 g (0.05 mol) of 2-pyrrolidino-4-methyl-5-n-butyl-6-hydroxypyrimidine are added and it is allowed to dissolve . The solution is then evaporated to dryness. The resulting solid is suspended in benzene and 8.48 g (0.05 mol!) Of 1-pyrrolidine sulfonyl chloride are added. The mixture is then refluxed for 2½ hours, allowed to cool and filtered. The filtrate is washed with water, 10% sodium hydroxide solution and again with water until the washing liquids give a neutral reaction. The product is dried over magnesium sulfate, the magnesium sulfate is filtered off and the solution is evaporated to dryness. Yield of product 10.79 g (58.6%), melting point 88 ^° C.

Example 5

This example illustrates the preparation of the compound of the formula:

/ 1C ₄ H ₉

40

45

(Compound No. 14 in Table I)

32.1 g (0.11 mol) of 2-ethylamino-4-methyl-5-n-butyl-6-hydroxypyrimidine and 4.0 g (0.1 mol) of sodium hydroxide are mixed in 300 cm ^{3 of} toluene and heated reflux the mixture to remove the water formed during the preparation of the sodium salt of 6-hydroxypyrimidine.

1435 g (0.1 mol) of dimethyl sulfamoyl chloride in 40 cm ^{3 of} toluene are added and the entire mixture is refluxed for 3 1/2 hours, after which it is cooled. The solution is washed three times with sodium hydroxide solution (200 cm ³ of 10% strength Solution) and then twice with water (200 to ³ ). The solution is then dried with anhydrous magnesium sulfate and the toluene is distilled off. A dark brown oil results in a yield of 22.15 g (70%). Refractive index / ι 2Ί, 5146.

The connections with the numbers 1,6,7,13,14,15, 16, 18 and 20 in Table I can be used in an analogous manner

be prepared, taking the appropriate substituted pyrimidine and the corresponding substituted sulfamoyl chloride used

12th

Fungicidal effect

The compounds of the invention are tested against a number of leaf diseases, which caused by fungi. The technique used consists in that one does not see the foliage diseased plants were sprayed with a solution of the test compound. All solutions for spraying contain 100, 25, 10, 5 and 1 parts by weight of test compound per million parts by weight of solution. the Plants are then infected with the diseases that it is desired to control and after one The period of days, which depends on the particular disease, becomes the extent of the disease visually assessed. The results are given in Tables HA and HB below, where the Extent of the disease is given in the form of the following classification.

Connection no.
(Table I)

classification

Percentage extent of the disease

61 to 100

26 to 60

6 to 25

0 to 5

illness and plant time Disease interval Code letter (Days) (Table HA)

Uncinula necator 10 Share each A. (Wine) Erysiphe graminis 7th B. (Wheat) Podosphaera leucotricha 10 C. (Apple) Sphaerotheca fuliginea 7th D. (Cucumber) Compound No. Table HA (Table I) (100 Million [ppm])

In Table II the disease is given in the first column and the second column is the time indicated what elapsed between infecting the plants and assessing the extent of the disease.

Table II

"rank code letter

1
2
3
4th
5
6th
7th
8th
9
10
Ii

3 3 3 3 3 3 3 3 3 0 3 3 3 3 3 3 3 2 3 3 0 - 3 3 - 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3

Table HA

(100 parts per million [ppm])

Disease Code Letter

3 3 3 3 3 0 3 3 2 - 3 3 1 - 3 3 3 - 3 3 0 - 1 3 2 - 3 3 3 - 3 3 3 - 3 3 1 - 3 3 3 3

12 13 14 15 16 17 18 19 20 24 25 "-" means not checked.

The above results clearly show that the compounds of the invention against various Types of powdery mildew are effective.

The following table HB shows the fungicidal action of the compounds according to the invention compared to those known compounds from GB-PS 82 584, with even lower concentrations of active ingredient in parts per million (ppm).

Table HB

Ver on illness of the binding
No bring-
rate powdery mildew cucumber Apple wine (ppm)

25th

10

25th

10

25th

10

25th

10

25th

10

25th

10

25th

10

3 3 3 0 1 0 3 3 3 3 3 1 3 3 3 3 1 1 3 1 3 3 3 3 3 3 3 2 3 0 2 0 2 0 3 3 3 0 3

3 3 3

3 3 3

3 3 3

2 3

3 2 3 3 2

3 3 3

AuI- 13th 22 46 - 3 cucumber 645 14th Apple wine cucumber (ppm) Other toxicity data bring-
rate - On- sickness 25 25 3 - - Effect on skin and eyes of Ver - Toxicity data for compounds in the table 3 bond
No rate 10 3 - - Rabbits binding
No. (ppm) illness powdery flour of the - Connection no. - 5 0 - - 25th Apple wine - 1 2.5 1 Slight skin irritation. Moderate eyes 10 - or trade name 3 Dimethiri- 25 2 0 3 irritation 3 5 3 3 of the product - mo! *) 10 - 3 No skin irritation. Mild eye irritation 25th - 1 - 5 10 3 Slight skin irritation. Mild eyes 10 3 1 1 3 1 0-1 irritation Π 5 3 0 1 '5 Elhirimol *) 25 3 0 3 No skin irritation. No eyes 25th 2 _ 4th 1 10 0 0 2 irritation 10 1 0 7th 3 5 0 0 2 No skin irritation. No eyes 14th 5 3 1 _ 1 0-1 irritation 25th - 0 10 0 *) Dimethirimol and Kthirimol are compounds no.4 Not toxic to honey bees 10 3 3 3 and 30 of Table 1 of GB-PS 1 182 584. 16 5 3 - 14th 1 25th
10 _ 0 3 The above results clearly show that the inven 1 U
5 1 Dimethirimol compounds according to the invention have a broader effect 18th 25th 3 2 1 spectrum and partially lower application 10 1 - mation rates need good than those already recognized 19th 5 3 2 3 effective pyrimidine fungicides of GB-PS 1182 584. - - The following Table III shows that the toxicities of the 25th 0 - 0, ο Compounds according to the invention in the same size 10 2-3 order of magnitude like that of the well-known 20th 5 3 1 Dimethirimols. 25th - 0 10 2 1 compared with dimethirimol 24 5 3 LD ₅₀ values (female rats); 3 oral administration 1 - in mg of compound per kg Table HI Body weight > 500 > 500 > 500. > 500 > 500 2350 mg / kg

Claims (4)

Patent claims: 1. 2-Amino-4-hydroxy-pyrimidine suifamic acid ester of the general formula 1 OSO, NR ⁵ R ⁶ (D in which either R ^{1 is} a hydrogen atom or a lower alkyl radical and R ^{2 is} a lower alkyl or allyl radical or R ¹ and R ² together with the nitrogen atom attached to these groups are a pyrrolidine ring, R ^{3 is} a lower alkyl radical, R ^{4 is} a butyl , Allyl or propargyl _{radical and either R 5} and R ₆ independently of one another each represent a lower alkyl or allyl radical or R ⁵ and R ⁶ together with the nitrogen atom bonded to these groups represent a pyrrolidine, morpholine or N-methylpiperazine ring. 2. Pyrimidinesulfamic acid ester according to claim 1, characterized in that R ¹ and R ^{2 have} the meaning given in claim 1, R ^{3 is} a methyl radical, R ^{4 is} a butyl radical and either R ⁵ and R ^{b are} a methyl or ethyl radical or together with the neighboring Nitrogen atom mean a pyrrolidino ring. 3. 2-Ethylamino-4-hydroxy-5-butyl-6-methyl-pyrimidine-N.N-dimethyl-sulfamic acid ester. 35 4. Process for the preparation of the compounds according to claim 1, characterized in that one a 4-hydroxypyrimidine of the general formula II