AU636240B2

AU636240B2 - Bisguanidines and fungicides containing them

Info

Publication number: AU636240B2
Application number: AU82607/91A
Authority: AU
Inventors: Eberhard Ammermann; Gisela Lorenz; Thomas Mueller; Matthias Zipplies
Original assignee: BASF SE
Current assignee: BASF SE
Priority date: 1990-08-20
Filing date: 1991-08-21
Publication date: 1993-04-22
Anticipated expiration: 2011-08-21
Also published as: DE4026273A1; AU8260791A

Description

P/00/011 281501 1 Regulation 3.2(2)

'AUSTRALIA

Patents Act 1990

ORIGINAL

COMPLETE SPECIFICATION STANDARD PATENT Application Number: Lodged: 000 06 *0 go BISGUANIDINES AND FUNGICIDES CONTAINING THEM Invention Title: em S.

4 *0 St S

S.

SO S The following statement is a full description of this invention, including the best method of performing it known to Us

S

555q5@ 0 S. S S SO 1 O.Z. 0050/41835 Biscuanidines and fungicides containing them The present invention relates to novel bisguanidines with a fungicidal action and to fungicides containing them.

GB 1,114,155 discloses the compound NH NH II II

H

2

N-C-NH-(CH

2 8

-NH-(CH

2 8

-NH-C-NH

2 and its fungicidal action.

Also known to have a fungicidal action are a,wbis(3,4-dichlorobenzylguanidino)alkanes McKay et al., J. Med. Chem. 6 (1963) 587).

NH NH C N(CH 2) n-NN C I CI H H H C Cl^

^C

n 10, 11, 1- Other guanidines are known from U.S. 3,468,898, *DE 39 22 232.2, EP 338,430, G.B. 935,614 and EP 406,699.

However, the action of these compounds is not always :satisfactory, especially at low application rates and concentrations.

We have now found that bisguanidine derivatives of the formula I .0 SS CS C, C. C

C

R -NH YNH-(CH 2)n-X-(CH 2)n-NH NH-R 1 R2-N

N-R

2 where

R

1 and R 2 are each, independently of one another, hydrogen, C 3

-C

10 -alkenyl, C 3 -C,,-alkynyl, Ci-Ca-alkoxy-C 2 -C.-alkyl, C 3 -Cl-haloalkenyl; or cycloalkyl which has 5 12 carbon atoms in the ring and can carry up to three of the following substituents: hydroxyl, Ci-Co 1 -alkyl, CI-C 10 alkoxy, Ci-Clo-haloalkyl and Ci-C 8 -alkoxy-Ci-C 8 alkyl; or benzyl which can be substituted up to three times by Ci-Co-alkyl or Ci-Co 1 -alkoxy, it being 2 possible for the cuostituent also to carry a hydroxyl or C 1 -C6-alkoxy group; or the benzyl is substituted by Ci-Clo-haloalkyl, with the proviso that only one of R1 and R2 can be hydrogen; or Ri and R2 are, together with the atoms which they substitute, a 5- to 11membered heterocyclic ring which can be substituted once to three times by Ci-Clo-alkyl or C 1 -Ca-alkoxy-C 1

-C

8 -alkyl; X is CH 2 O, a single bond, NH, N-(Ci-Clo-alkyl) or N-benzyl whose phenyl can be substituted once to three times by C 1 -Cio-alkyl, Ci-

C

l o -alkoxy, Ci-Clo-haloalkyl or halogen, and n is 5 to 8, and their plant-compatible acid addition salts and their metal complexes, have an excellent fungicidal action against phytopathogenic fungi.

If R1 or R2 is hydrogen, the compounds can exist in tautomeric forms which are covered by the invention.

With a view to their fungicidal action, the preferred compounds are those in which the substituents have the following meanings: R1, R2 hydrogen, with the proviso that not less than one of R1 and R2 is different from hydrogen; Cs-Clo-alkenyl or C 3 -Clo-alkynyl, especially allyl, dimethylallyl or2butynyl;

C

1 -Ca-alkoxy-C 2 -C-alkyl, especially methoxyethyl, tert.

butoxyethyl or methoxypropyl; C3-Clo-haloalkenyl, especially 3-bromo-2-propenyl, 2-bromo-2propenyl or 3-chloro-2-propenyl; cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl and cyclododecyl, it being possible for these to carry up to three of the following: hydroxyl;

C

1 -Clo-alkyl, especially methyl, ethyl, propyl, 3 O.Z. 0050/41835 isopropyl, butyl, isobutyl, sec.-butyl, tert.butyl, 1, 1-dimethyipropyl or 2,4, 4-trimethyl- 2-pentyl;

C

1 -Cl-alkoxy, especially methoxy, ethoxy, isopropoxy, n-butoxy, tert.-butoxyoroctyloxy; Cl-C 4 -haloalkyl, especially trifluoromethyl or pentafluoroethyl;

C

1

-C

8 -alkoxy-Cl-C.-alkyl, especially methoxymethyl, ethoxymethyl, methoxyethyl, tert. butoxymethyl or 1-methoxy-l-methylethyl; or benzyl, which can carry up to three of the following substituents: Cl-Cl.-alkyl, especially methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec.-butyl, tert.butyl, 1, 1-dimethylpropyl, 2, 3-dimethyipropyl, 1, 2 -trimethylpropyl, 2 -hydroxy- 2-propyl or 2 9....methoxy-2-propyl;

CC

10 aloy especially methoxy, ethoxy, isopropoxy, n-butoxy, tert.-butoxy or octyloxy; 64: 2 Cl-C-haloalkyl, especially trifluoromethyl or pentafluoroethyl; particularly preferred for R 1 and R 2 are hydrogen, with the proviso that not less than one of R 1 and R 2 is dif ferent. from hydrogen, cyclopentyl, cyclohexyl, cycloheptyl, 7 5 2-methylcyclohexyl, 3-methylcyclohexyl, 3-trifluoromethylcyclohexyl, 3, 3-dimethylcyclohexyl, 4-tert. -butylcyv lohexyl, 4-methylbenzyl, 4-ethylbenzyl, 4-isopropylbenzyl, 4-tert. -butylbenzyl, 4- 2-trimethyipropyl) benzyl, 2, 4-dimethylbenzyl, 4-methoxybenzyl, 4-tert. butoxybenzyl or 3,4-dimethoxybenzyl;

:R

1 and R 2 are, together with the atoms which they substitute, a 5- to il-membered heterocyclic ring, especially an imidazolinyl, tetrahydropyrimidyl, tetrahydro-1, 3-diazepinyl, hexahydro-1, 3diazocinyl or hexahydro-l,3-diazoninyl, it being possible for these to carry up to three of the following substituents: 4 O.Z. 0050/41835 Cl-Cl 0 -alkyl, especially methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec. butyl, tert. -butyl, 1, 1-dimethylpropyl or 2,4, 4-trimethyl-2-pentyl; C,-C-alkoxy-C-C.-alkyl, especially methoxymethyl, ethoxymethyl, methoxyethyl, tert. butoxymethyl or 1-methoxy- 1-methylethyl; particularly preferred for R 1 and R 2 are imidazolinyl, tetrahydropyrimidyl, 4,4dimethyltetrahydropyrimidyl, 5-tert. -butyltetrahydropyrimidyl or hydro-l, 3-diazocinyl X is CH 2 1 0, a single bond, NH, N-(Cl-Cl.-alkyl), especially N-methyl, N-ethyl, N-propyl, Nisopropyl, N-butyl, N-isobutyl, N-sec. -butyl, N-tert -butyl or N-i1, 1-dimethylpropyl, N-benzyl none* *whose phenyl can be substituted by Cl-C 1 0 -alkyl, especially methyl, ethyl, propyl, isopropyl, :butyl, isobutyl, sec.-butyl, tert.-butyl, 1,1- 20 dimethylethyl, 1,1-diniethylpropyl, 2,3so dimethylpropyl, 1, 1,2-trimethylpropyl,

C

1

-C

10 alkoxy, especially methoxy, ethoxy, isopropoxy, n-butoxy, tert.-butoxy or octyloxy, C 1 -Cl 0 loons:haloalkyl, especially trifluoromethyl or 4025 pentafluoroethyl, or halogen, especially fluozine, chlorine or bromine; particularly preferred for X are CH 2 1 NH, Nso methyl, N-ethyl, N-benzyl, N-4-tert. -butylbenzyl, 1,1, 2-trimethylpropyl)benzyl, Nloon: 304-methoxybenzyl, N-4-tert. -butoxybenzyl, N-4chlorobenzyl, N-4-fluorobenzyl or a single bond; Also preferred are compounds in which R1 and R 2 are, independently of each other, hydrogen or cycloalkyl, as defined above, and X is NH. Compounds in which RI and R 2 together denote imidazolinyl or tetrahydropyrimidinyl and X is NH or a single bond are also preferred.

suitable acid addition salts are the plant- 5 O.Z. 0050/41835 compatible salts of those acids which do not impair the fungicidal action of I, eg. iodides, chlorides, bromides, sulfates, dodecyl sulfates, nitrates, carbonates, phosphates, borates, formates, acetates, propionates, benzoates, oxalates, naphthalenesulfonates, dodecylbenzenesulfonates, lactates, citrates and the salts with the saccharin anion.

Suitable metal complexes are those of copper, zinc, tin, manganese, iron, cobalt or nickel. The complexes are preferably prepared from the free bases I and the salts with mineral acids, for example the chlorides or sulfates, of the metals.

The bisguanidines I can be prepared in a variety of ways, the following methods being preferred: 15 a) preparation from isothiuronium salts and diamines R1-NH S-R3 2 N Y II

R

2

H

I *HY, H2N-(CH 2 )nnX- n-H2 II In these formulae, R 3 is benzyl or C 1

-C

4 -alkyl, eg.

methyl or .thyl, and Y' is chloride, bromide, iodide, sulfate, methosulfate, methanesulfonate or tosylate.

The starting compounds II and III are known or can be obtained in a known manner (for the isothiuronium salts, see Houben-Weyl, Methoden der Organischen Chemie, 4th edition, Vol. IX, pp. 900 et seq.).

The reaction of isothiuronium salts with diamines 25 which is shown in the diagram and is known (eg.

A.V. Bogatskii et al., Khim.-Farm. Zh. 17 (1983) 308; CA 98 215574z) to give bisguanidine compounds I-HY' is preferably carried out in polar solvents such as alcohols, ketones, ethers, nitriles, dimethyl sulfoxide, Nmethylpyrrolidone, dimethylformamide or dimethylacetamide.

The reaction is generally carried out with from to 4.0 moles, particularly preferably 2.0 moles, of isothiuronium salt II per mole of diamine III. It is also 6 O.Z. 0050/41835 possible to have a tertiary amine such as triethylamine present as additional base. In this case, equimolar amounts of additional base and of isothiuronium salt are preferably employed.

The reaction can be carried out at from 20 0 C to the boiling point of the solvent, preferably from 60 to 130°C.

The reaction is preferably carried out under atmospheric pressure.

Anion exchange can be used to obtain salts with other anions or, by replacement by hydroxyl ions, the free bases I.

b) Preparation from aminoiminomethanesulfonic acids and diamines

R

1 -NH- SO 3

H

2 N H2N-(CH2)n-X-(CH2)n-NH 2

I

15 R2 S IV III *e The starting compounds IV are known or can be prepared from thiourea derivatives in a conventional manner (eg. C.A. Maryanoff et al., J. Org. Chem., 51 (1986) 1882).

.20 Suitable temperatures for the reaction are from 0 C leec..

to the boiling point of the solvent.

The ratios of amounts and the pressure are the same as for method a).

The solvents are the same as for method a) but acetonitrile is very particularly preferred.

c) Preparation from carbodiimides and diamines C. 2 R1-N=C=N-R2 V

H

2

N-(CH

2 )n-X-(CH 2 )n-NH2 III The starting compounds V are known or can be prepared by known processes (cf. eg. M. Mikolaiczyk, Tetrahedron 37 (1981) 233).

7 O.Z. 0050/41835 It is advisable to employ for the reaction 2 moles of carbodiimide V per mole of diamine III, but it is preferable to use a small excess of amine or carbodiimide, of up to about 10%, over the 1 2 ratio.

Suitable solvents for the reactions are hydrocarbons such as hexane or toluene, short-chain alcohols such as isopropanol or tert.-butanol, amides such as dimethylformamide or nitriles such as acetonitrile.

The temperature and the pressure are the same as for method a).

d) Preparation from imidocarbonates and amines

+RI-NH

2 VIIa H 2

N-(CH

2 )n-X-(CH 2 )n-NH 2 Ill

R

4

HY'

IHY'

R

5 -Z Z-R 5

HY'

VI

+R2-NH 2 VIIb H 2

N-(CH

2 )n-X-(CH 2 )n-NH 2

III

When Z 0 in this formula, R 4 is cyano, benzoyl or methanesulfonyl, and R 5 is phenyl, and when Z S, R 4 is S. 15 cyano and R 5 is methyl.

The reaction of imidocarbonates with two amines is known (cf. eg. A. Buschauer, Arzneim.-Forsch./Drug. Res., 37 (1987) 1003, 1008; Arch. Pharm., 321 (1988) 281) and is carried out in two separate stages. The imidocarbonate is preferably reacted with the first amine in a chlorohydrocarbon such as dichloromethane, an ether such as diethyl ether or tetrahydrofuran, a short-chain alcohol such as methanol or isopropanol, a water/alcohol mixture such as water/methanol or a nitrile such as acetonitrile.

The reaction of the product with the second amine is then carried out in a polar solvent such as methanol, ethanol, S. isopropanol, tert.-butanol, pyridine or acetonitrile.

It is advisable to employ for the reactions 1.0 mole of amine VIIa or VIIb and 0.5 mole of diamine III per mole of imidocarbonate VI, but a small excess of amine, of up to about 10%, is preferably used.

The temperature and pressure are the same as for 8 O.Z. 0050/41835 method a).

The resulting compounds are hydrolyzed in a conventional manner, advantageously in a mineral acid or an organic carboxylic acid at, for example, 70 to 120 0

C.

Preferably used is 2 to 10 M hydrochloric acd or 50 to strength acetic acid.

The chlorides or acetates of the compounds I with R 1 or R 2 equal to hydrogen are obtained.

The free bases I are prepared as in method a).

e) Preparation from cyanogen bromide and amines +R1-NH 2 VIIa H2N-(CH2)n-X-(CH2)n-NH2-HY'

III.H/'

-NH-CN VIIIa- Br-CN I.gy Br N H2N- CH 2 n-X-(CH2)n-NH2'HY' III*HY'- 2 -NH-CN VIIIb +R2-NH 2 VIIb tee. 2 Br-CN *se H2N-(CH 2 )n-X-(CH 2 )n-NH 2

NC-NH-(CH

2 )n-X-(CH 2 )n-NH-CN III

IX

s +RI-NH 2 HY' VIIa*HY' OR.

IHY'

+R-NH

2 *HY' VIIb-HY' Y' in these formulae is preferably chloride.

The reaction of cyanogen bromide with amines, which is known from Houben-Weyl, Methoden der Org.

Chemie, 4th edition, Vol. E4, p. 981, to give N-substitnted cyanamides is preferably carried out in a two-phase system, eg. water/dichloromethane, or else anhydrous in inert solvents such as diethyl ether, tetrahydrofuran, dioxane, dichloromethane or toluene.

:20 The reactions are preferably carried out at from -20 to +10 0

C.

The ratios of amounts and the pressure are the same as for method d).

The reaction of the N-substituted cyanamides VIIIa, VIIIb and IX, which is known from Houben-Weyl, Methoden der Org. Chemie, 4th edition, Vol. E4, p. 609, 9 O.Z. 0050/41835 with the hydrochlorides of the amines III, VIIa and VIIb is preferably carried out without solvent at, for example, from 130 to 250 0

C.

The amounts, the pressure and the preparation of the free bases I are the same as for method d).

The compounds I with R 1 or R 2 equal to hydrogen are obtained.

The compounds of the formula I and the salts and metal complexes thereof are suitable as fungicides and are well tolerated by plants.

PREPARATION EXAMPLES EXAMPLE 1 Method a) (compound lla) 1,13-Bis(3,3-dimethylcyclohexylguanidino)-7-azatridecane dihydroiodide

H

e. NH, NH-(CH2)6-NH-(CH2)6-NH NN 2 HI Qe Q- N° 2 HI

CH

3

CH

3 CH 3

CH

3 A mixture of 16.4 g (0.050 mol) of 3,3-dimethylcyclohexyl-S-methylisothiuronium iodide, 5.3 g (0.025 mol) of 1,13-diamino-7-azatridecane, 5 g (0.050 mol) of triethylamine and 15 g of molecular sieves (4 A) in 200 ml 20 of anhydrous acetonitrile was refluxed under a nitrogen atmosphere for 48 hours, with elimination of methanethiol. The mixture was filtered hot and the compound was isolated from the solution.

Yields 93% of theory; melting point 120 0

C.

Precursor Al \3,3-Dimethylcyclchexyl-S-methylisothiuronium iodide QrF NHM-SMe I J lI HI X NH A solution of 63 g (0.339 mol) of 3,3-dimethylcyclohexylthiourea and 48.1 g (0.339 mol) of iodomethane 10 O.Z. 0050/41835 in 100 ml of methanol was refluxed for 1 hour. The solvent was distilled out under reduced pressure to leave a yellow resinous solid.

Yield: 58% of theory, melting point Precursor A2 3,3-Dimethylcyclohexylthiourea Qx NHH2 59 g (0.42 mol) of benzoyl chloride were added dropwise over the course of 10 minutes to a solution of 33 g (0.44 mol) of ammonium thiocyanate in 100 ml of absolute acetone. The mixture was refluxed for 10 minutes and then 50.8 g (0.40 mol) of 3,3-dimethylcyclohe..ylamine were added dropwise, and the mixture was refluxed for a S* further 20 minutes and then stirred into 500 ml of ice- 15 water. The precipitated solid was filtered off with suction, washed with water, dissolved in a hot mixture of 500 ml of 10% strength sodium hydroxide solution and 125 ml of ethanol and refluxed for 30 minutes. The reaction mixture was then diluted with ice-water, and the pH was initially adjusted to 1 with concentrated hydro- S" chloric acid and then to 9 with solid sodium bicarbonate.

The resulting precipitate was filtered off with suction, 6. washed with water and dried at 80*C under reduced pressure.

Yield: 85% of theory; melting point 153 0

C.

EXAMPLE 2 (Compound 18a) 1,17-Biscyclohexylguanidino-9-azaheptadecane triacetate ~a NHINH-(CH 2 8

-NH-(CH

2 8-NHNH Q3 CH 3

COOH

NH

11 O.Z. 0050/41835 10.2 g (0.011 mol) of 1,17-biscyclohexylguanidino-9-azaheptadecane dihydroiodide in 150 ml of methanol/water (1 1) were filtered through a column containing 250 g of ion exchanger (OH- form). The free guanidine base obtained after working up was dissolved in methanol and converted into the triacetate with excess glacial acetic acid.

EXAMPLE 3 Method a) (compound 16a) 1,17-Biscyclohexylguanidino-9-azaheptadecane dihydroiodide 2 NHrNH-(CH2)8-NH-(CH2)8-NH NH-C .2 HI NH NH A mixture of 30.0 g (0.10 mol) of cyclohexyl-S- *e.o methylisothiuronium iodide, 13.6 g (0.05 mol) of 1,17diamino-9-azaheptadecane, 10.0 g (0.10 mol) of triethylamine and 20 g of molecular sieves (4 A) in 300 ml of anhydrous acetonitrile was refluxed under a nitrogen atmosphere for 5 days, methanethiol being eliminated. The mixture was filtered hot and worked up as usual.

Yield: 43% of theory; melting point 170"C.

Precursor B1 Cyclohexyl-S-methylisothiuronium iodide Ia N.-SMe HI

NH

h eA solution of 62.0 g (0.392 mol) of cyclohexyl- *'25 thiourea and 55.7 g (0.392 mol) of iodomethane in 300 ml of methanol was refluxed for hour. After cooling to room temperature, the product w, precipitated by adding methyl tert.-butyl ether, filtered off with suction, washed with methyl tert.-butyl ether and hexane and finally dried at 50"C under reduced pressure.

12 O.Z. 0050/41835 Yield: 68% of theory; melting point 115 120"C.

Precursor B2 Cyclohexylthiourea

H

NH

2 295.5 g (2.1 mol) of benzoyl chloride were added dropwise over the course of 10 minutes to a solution of 165.0 g (2.2 mol) of ammonium thiocyanate in 500 ml of absolute acetone. After refluxing for 10 minutes, 198.9 g mol) of cyclohexylamine were added dropwise, and the mixture was refluxed for a further 20 minutes. It was then stirred into 4 1 of ice-water, and the water was decanted off the oily product. The residue was dissolved in a hot mixture of 2 1 of 10% strength sodium hydroxide solution and 500 ml of ethanol and refluxed for :15 minutes. The reaction mixture was then diluted with icewater, and the pH was adjusted initially to 1 with econcentrated hydrochloric acid and then to 9 with solid sodium bicarbonate. The resulting precipitate was filtered off with suction, washed with water and dried at 80"C under reduced pressure.

Yield: 78% of theory; melting point 135"C.

EXAMPLE 4 Method c) (compound 14a) S1,13-Bis(N,N'-dicyclohexylguanidino)-7-azatridecane trihydrochlorida (NH-(CH2)6-NH-(CH2)6-NH NH*3

HCI

A mixture of 49.4 g (0.24 mol) of dicyclohexylcarbodiimide, 21.5 g (0.10 mol) of 1,13-diamino-7-azatridecane and 400 ml of anhydrous tert.-butanol was refluxed 13 O.Z. 0050/41835 for 12 hours. The isolated oily product was mixed with methanolic hydrochloric acid and the solvent was removed by distillation under reduced pressure, leaving a colorless solid.

Yield: 26% of theory; melting point 140 0

C.

EXAMPLE (Compound 1,12-Bis(2-amino-3,4,5,6-tetrahydropyrimidyl)dodecane diacetate H H NH-(CH2)12-NH N 2 CH 3

COOH

30.0 g (0.048 mol) of l,12-bis(2-amino-3,4,5,6tetrahydropyrimidyl)dodecane dihydroiodide in 300 ml of methanol/water (1 1) were filtered through a column containing 250 g of ion exchanger (OH' form). The free guanidine base obtained after working up was dissolved in methanol and converted into the diacetate with excess glacial acetic acid.

EXAMPLE 6 Method a) (compound 34b) 1,12-Bis(2-amino-3,4,5,6-tetrahydropyrimidyl)dodecane dihydroiodide 4 H

H

NH-(CH2)12-NH N 2 HI 9 A mixture of 103.3 g (0.4 mol) of 2-S-methyl- 3,4,5,6-tztrahydropyrimidinium iodide, 40.0 g (0.2 mol) 25 of 1,12-diaminododecane, 20.2 g (0.2 mol) of triethylamine and 60 g of molecular sieves (4 K) in 1 1 of anhydrous acetonitrile was refluxed under a nitrogen atmosphere for 16 hours, with elimination of methanethiol. The mixture was filtered hot and then worked up as usual.

Yield: 81% of theory of a brown oil 14 O.Z. 0050/41835 IR (film): 3217, 2925, 2853, 1642, 1315 cm'1 Precursor D1 2-S-IMethyl-3, 4,5, 6-tetrahydropyrirnidyl isothiuroni~um iodide N-y- SMe HI

CNC

A solution of 50.0 g (0.431 mol) of perhydropyrimidinethione and 61.2 g (0.431 mol) of lodomethane in 200 ml of methanol was ref luxed for 1 hour. After cooling to room temperature, the product was precipitated by adding methyl tert.-butyl ether, filtered off with suction, washed with methyl tert. -butyl ether and dried.

Yield: 94% of theory; melting point 135*C *Got 6.6.

00000: a. SW 4 4 .4 6 0 4 4 q 0 r.a *.e 0 4 L 4 A 4 40 ae S 6 @6 S 0 6 6 40, 0 40 9 400 0644 60 0 4 .9 S 6 4 0 0 09000 00 44440 480 d~ 4 TABLE 1 R 2

N,

Comp. No. X n HY m.p./IR(film) [clif'] la 2a 3a 4a 6a 7a 8a 9a lla 12a 1.3a Cyclohexyl Cyc lohexyl Cyclohexyl Cyc lohexyl Cyclopentyl Cyclooctyl Cyclododecyl 4-tert. -Butylcyclohexyl 4-Isopropylcyclohexyl 3-Trifluoromethylcyclohexyl 3, 3-Diiethylcyclohexyl Cyc lohexyl Cyc lohexyl

H

CylHey Cyc lohexyl HC1

CH

3

COOH

C

2

H

2 0 4 125 0

C

100oac 140 0

C

HI 120 0

C

2926, 2851, 1639, 1448,

CH

3 COOH 3205, 3085, 2930, 2855, 1612, 1573, 1450, 1400, 1366, 1246 0 0 0 U .0 0 C a a

S

tag ow.

a t~ a p 0' 0 a ow a am a a o ow 00Y 40 a we -4 0 or a 6 6 .aa Comp. No.

14a 16a 17a 18a 19a 21la 22a 23a 24a 26a 27a 28a 29a Cyc lohexyl Cyc lohexyl Cyc lohexyl Cyc lohexyl Cyc lohexyl Cyclohexyl Cyc lopentyl TABLE 1 Continuation Rz X n HY in.p./IR(film) [cm'1] Cyclohexyl NH 6 HC1 140 0

C

H NH 8 3279, 3185, 2929, 2854, 1652 H NH 8 HI 170 172*C H NH 8 IHC1 110 0

C

H NH 8 CH 3 COOH 98 -100-C H NH B C 2

H

2 0 4 165 -167 0

C

H NH 8 Cyclooctyl Cyc lododecyl 4-tert. -Butylcyclohexyl 4- Isopropylcyclohexyl 3-Tn fluoromethylcyc lohexyl 3, 3-Dimethylcyclohexyl Cyc lohexyl Cyc lohexyl

H

Cyclohexyl

H

NH

single bond single bond Cyc lopentyl

S

f 0S S 4 a 9 See See S U a a S CC B C S S C S 9 C *5 eeC 0* 00 bee C0 SOS :0 *s 009 s CB BC TABLE 1 (Continuation) R 2 x Comp. No.

n HY m.p./IR(film)[cmf'] 3la.

32a 33a 34a 36a 37a 38a 39a 41Ia 42a 4 3a 44a 46a 47a 48a Cyc looctyl Cyclododecyl 4-tert. -Butylcyclohexyl 4 -Isopropylcyclohexyl 3 -Trifluoromethylcyclohexyl 3, 3-Dimethylcyclohexyl cyc lohexyl Cyc lohexyl Cyc lopentyl Cyclooctyl Cyc lododecyl 4-tert. -Butylcyclohexyl 4-Is oprcopylcyc lohexyl 3-Trifluoromethylcyc lohexyl 3, 3-Dimethylcyclohexy1 Cyc lohexyl Cyclohexyl Cyc lopentyl Cyc looctyl

H

Cyc lohexyl

H

Cyc lohexyl

H

single bond single bond single bond single bond single bond single bond single bond

CH

2

CH

2

CH

2

CH

2

CH

2

CH

2

CH

2

CH

2

CH

2 single bond single bond single bond S 5 0 CS 0 0 S S ~0 see C SS Comp. No. R X n HlY m.p./IR(film) [cmf 1 49a Cyclododecyl H single bond 6 4-tert.-Butylcyclohexyl H single bond 6 51a 4-Isopropylcyclohexyl H single bond 6 52a 3-Trifluoromethylcyclohexyl H single bond 6 53a 3,3-Dimethylcyclohexyl H single bond 6 54a Cyclohexyl Cyclohexyl single bond 6 p-tert.-Butylbenzyl H NH 6 56a p-tert.-Butylbenzyl Butyl NH 6 57a p-tert.-Butylbenzyl Cyclohexyl NH 6 co 58a p-(1,1,2-Trimethylpropyl)benzyl H NH 6 59a p-(1,l,2-Trimethylpropyl)- Cyclooctyl NH 6 benzyl p-tert. -Butoxybenzyl H NH 6 61a p-tert. -Butoxybenzyl Cyclohexyl NH 6 -0 62a p-tert.-Butylbenzyl H NH 8 63a p-tert.-Butylbenzyl Cyclohexyl NH 8 64a p-tert.-Butylbenzyl Cyclooctyl NH 8 0n p-Isopropylbenzyl H NH 8 66a p-Isopropylbenzyl 1,3-Dimethyl- NH 8 butane

C

0 00 0

C

S

.00 00.

C

C C *0 0 0 5 00 S *0 S S 00 05.

C SC S see SO 0 S .0 C C S S 0 C CO C C C S *s 5 0 TABLE 1 (Continuation) Comp. No. R R 2 X n HY m.p./IR(film) [cm- 1 67a 68a 69a 7Ua 71la 72a 7 3a 74a 76a 77a 78a 79a 8Bia 82a p-lMethoxybenzyl p-Methoxybenzyl p-tert. -Butylbenzyl p-tert. -Butylbenzyl p-Ethoxybenzyl p-Ethoxybenzyl p-tert. -Butylbenzyl p-tert.-Butylbenzyl p-tert Butylbenzyl p- 2-Trimethyipropyl) benzyl p- 2-Trimethyipropyl) benzyl p-tert. -Butoxybenzyl p-tert Butoxybenzyl p-tert. -Butylbenzyl p-tert. -Butylbenzyl p-tert.-Butylbenzyl

H

Propyl

H

Cyc lohexyl

H

Isopropyl

H

Cyc lohexyl Cyc looctyl

H

Cyclooctyl

H

NH

single bond single bond single bond single bond

CH

2

CH

2

CH

2

CH

2

CH

2

CH

2 1,2-Dimethyl- CH 2 propyl H single bond Butyl single bond Cyclohexyl single bond 0 *S :0 0 se D% .0 :0 0.0 TABLE 1 (Continuation) Comp. No. RR 2 X n HY m.p./IR(film) [cmf 1 83a p-tert.-Butoxybenzyl H single bond 6 84a p-tert.-Butoxybenzyl Cyclohexyl single bond 6 Cyclohtexyl H NMe 6 86a Cyclohexyl H N-CH 2 Ph 8 87a p-tert. -Butylbenzyl H N-Me 6 88a p-tert. -Butylbenzyl H 8 0 C0 In

C)

In 0 0 0 6 0 00 S S S S S S 6S *50

S..

*o *o @0 5. 6 6 6 0 5 0S 0 @6 @0 e 0 6 6 0 0 6 TABLE 2 fRI-N NH-CH)-X-(CH)n-NH -Rl'l

R

2 -N N-Ri,

HY

Comp No.

lb

R

2

-N

S.

x

NH-

m.p./IR(film) [cnf')1 I 95 0

C

N-k N) N 6 CH- 3 C001- 3165 3051, 2933, 2858, 1679, 1560, 1471, 1402, 1286

IOO

0

C

2

H

2 0 3225, 2930, 1643, 1316

H

~N

S

a q0 0

S

*SS S..

S S S S *S S S S 0 S S S S S ag 0* 0 9. 0.

*5* 50 4 I A S S S

S

TABLE 2 (Continuation) Comp No.

H

R2N

H

>CN

H

UN

m.p./IR(film) [cm- 1 3218, 2926, 2854, 1643, 1316

N

3308, 3236, 3160, 3057, 2812 1654 1634 1314 2929, 2853,

I

C

eei S SC C I 0 S C a S. S Ce S CCC IC Se C C C S SC C 6 5 C S C *5 C CS. 00059 CI. C C C TABLE 2 (Continuation) x n HY Comp. No M.P./IR(film) [cm- 1 R 2-N

H

C

8 CH- 3

COOH-

8 C 2 1i 2 0 4 3227, 3160, 2927, 2854, 1667, 1567, 1441, 1398, 1318 140 0

C

H

Ny

>,N

a a.

a a a a.a a a a sq a 5 6 a a. a a a .5 *64 a S 535 a. a 0 *m a S a a a a a a *o a a a a TABLE 2 (Continuation) x n HY Comp.No.

1 7b R2Nf

N,

m.p./IR(film) [cmuf']

H

>,N

single bond single bond single bond single bond

R

C S S C

S

*RU 5CR C C S S C S SC C C C 90 5 C 4 5 @5 C CC C See S C C C C St C 0 50 5 U S S S S C S C CO S S S S S Se, 5 5 9 Comp. No.

H TABLE 2 (Continuation)

RI-N

1 yX n 1W R -N m.p./IR(film) [cinf 1

N

single bond I

H-

N

B

0 00

B

0 *00 BBS 4 500 B BE S B 90 B B B S B *B *BS 5 OB BBB BOB 0 BE 0 0 B BB B 0 0 B B S B 0 B BO 000 BOB 00 0.0 B 0 Comp No.

27b HlN~ TABLE 2 (Continuation) x n HY m.p./IR(film) [cm- 1

H

Fi single bond single bond single bond 3284, 2916, 2849, 1637, 1612, 1556, 1470, 1262 197 0

C

3290, 3142, 3063, 3001, 2984, 2926, 2862, 2853, 1674, 1590 2926, 2854, 1677, 1560, 1396, 1285

H

6 CH 3 CQOisingle bond a.

a a a .4t *.e S S a a a *a a a a- a. a a E a a. a..

a *0 *aa aa a a S a a. a a S S S S a a a a a a a a a q TABLE 2 (Continuation) Comp. No.

H

R 2

-N

m.p./IR(film) [cm- 1

H

N

H

Nr or

C-IN

single bond single bond single bond 156 158 0

C

HCI

HI

3214, 3067, 2926, 2854, 1646, 1317 3217, 2925, 2853, 1642, 1315 single bond single bond single bond 6 CH 3

COOH-

6 C 2

H-

2 0 4 3231, 2928, 2855, 1660, 1558, 1275 140 142 0

C

U

UO

0

S

U

*0S *g* a S 55 a S US U S 0 .5 *5U 0 US.

S S U U i 0 S 06 5 9 0 US S 05004 S S US 065 U gUS S S U Comp. No.

TABLE 2 (Continuation) H1N~ x n HfY

R-N

In.P./IR(film) [cm- 1

H

N

single bond single bond N-Me N-CH-0 -6 29 O.Z. 0050/41835 The compounds are suitable as fungicides.

The fungicidal compounds and the agents containing them can be applied, for example, in the form of directly sprayable solutions, powders, suspensions, including concentrated aqueous, oily or other suspensions or dispersions, emulsions, oily dispersions, pastes, dusts, broadcasting agents or granules by spraying, atomizing, dusting, broadcasting or watering. The modes of application depend on the purposes for which they are used; they should ensure in all cases the finest possible dispersion of the active ingredients according to the invention.

The plants are normally sprayed or dusted with the active ingredients or the seeds of the plants are treated with the active ingredients.

The formulations are prepared in a conventional manner, for example by diluting the active ingredient with solvents and/or carriers, if desired using emulsifiers and dispersants, it being possible when water is used as diluent also to add organic solvents as cosolvents. Auxiliaries suitable for this purpose are S* essentially: solvents such as aromatic compounds (eg.

xyleni), chlorinated aromatic compounds (eg. chlorobenzenes), paraffins (eg. petroleum fractions), alcohols (eg. methanol, btanol), ketones (eg. cyclohexanone), amines (eg. ethanolamine, dimethylformamide) and water; carriers such as natural rock meals (eg. kaolins, S-aluminas, talc, chalk) and synthetic rock meals (eg.

highly €isperse silica, silicates); emulsifiers such as nonionic and anionic emulsifiers (eg. polyoxyethylene fatty alcohol ethers, alkylsulfonates and arylsulfonates) and dispersants such as lignin sulfite waste liquors and methylcellulose.

Suit ale surfactants are alkali metal, alkaline earth metal and ammonium salts of aromatic sulfonic acids, eg. lignin-, phenol-, naphthalene- and dibutylnaphthalenesulfonic acid, and of fatty acids, alkyl- and 30 O.Z. 0050/41835 alkylarylsulfonates, alkyl, lauryl ether and fatty alcohol sulfates, and salts of sulfated hexa-, hepta- and octadecanols, and of fatty alcohol glycol ethers, products of the condensation of sulfonated naphthalene and its derivatives with formaldehyde, of naphthalene or of naphtaalenesulfonic acids with phenol and formaldehyde, polyoxyethylene octylphenol ethers, ethoxylated isooctyl-, octyl- or nonylphenol, alkylphenol and tributylphenyl polyglycol ethers, alkylaryl polyether alcohols, isotridecyl alcohol, fatty alcohol/ethylene oxide condensates, ethoxylated castor oil, polyoxyethylene alkyl ethers or polyoxypropylene, lauryl alcohol polyglycol ether acetate, sorbitol esters, lignin sulfite waste liquors or methylcellulose.

Powders, dusts and broadcasting agents can be prepared by mixing or milling together the active substances with a solid carrier.

Granules, eg. coated, impregnated or homogeneous granules, can be prepared by binding the active ingredi- 20 ents to solid carriers. Solid carriers are mineral earths such as silica gel, silicic acids, silicates, talc, 0* kaolin, limestone, lime, chalk, bole, loess, clay, dolomite, diatomaceous earth, calcium and magnesium sulfate, magnesium oxide, milled synthetic materials, fertilizers such as ammonium sulfate, ammonium phosphate, ammonium nitrate, urea and vegetable products such as cereals meal, bark, wood and nutshell meals, cellulose powder or other solid carriers.

SExamples of such formulations are: 30 I. a solution of 90 parts by weight of compound No.

12a and 10 parts by weight of N-methyl-a-pyrrolidone, which is suitable for use in the form of very small droplets; II. a mixture of 20 parts by weight of compound No.

14a, 80 parts by weight of xylene, 10 parts by weight of the adduct of 8 to 10 moles of ethylene oxide and 1 mole of oleic acid N-monoethanol- 31 O.Z. 0050/41835 *do* 6 asg.

.20

C

SdSSr C. S 5

C.

S.

amide, 5 parts by weight of calcium dodecylbenzenesulfonate, 5 parts by weight of the adduct of 40 moles of ethylene oxide and 1 mole of castor oil; the solution is finely dispersed in water; III. an aqueous dispersion of 20 parts by weight of compound No. 30b, 40 parts by weight of cyclohexanone, 30 parts by weight of isobutanol, parts by weight of the adduct of 40 moles of ethylene oxide and 1 mole of castor oil; IV. an aqueous dispersiei of 20 parts by weight of compound No. 31b, 25 parts by weight of cyclohexanol, 65 parts by weight of a mineral oil fraction of boiling point 210 to 280°C and parts by weight of the adduct of 40 moles of ethylene oxide and 1 mole of castor oil; V. a mixture, milled in a hammer mill, of 80 parts by weight of compound No. 35b, 3 parts by weight of sodium diisobutylnaphthalene-a-sulfonate, parts by weight of the sodium salt of a ligninsulfonic acid from a sulfite waste liquor and 7 parts by weight of powdered silica gel; the mixture is finely dispersed in water to give a sprayable composition; VI. an intimate mixture of 3 parts by weight of compound No. 31b and 97 parts by weight of finely divided kaolin; this dust contains 3% by weight of active ingredient; VII. an intimate mixture of 30 parts by weight of compound No. 12a, 92 parts by weight of powdered silica gel and 8 parts by weight of liquid paraffin which has been sprayed onto the surface of this silica gel; this preparation confers good adhesion on the active ingredient; VIII. a stable aqueous dispersion of 40 parts by weight of compound No. 14a, 10 parts by weight of the sodium salt of a phenolsulfonic C o

OS

0 32 O.Z. 0050/41835 acid/urea/formaldehyde condensate, 2 parts by weight of silica gel and 48 parts by weight of water, which can be further diluted; IX. a stable oily dispersion of 20 parts by weight of compound No. 14a, 2 parts by weight of calcium dodecylbenzenesulfonate, 8 parts by weight of fatty alcohol polyglycol ether, 20 parts by weight of the sodium salt of a phenolsulfonic acid/urea/formaldehyde condensate and 68 parts by weight of a paraffin mineral oil.

The compounds have excellent activity against a wide spectrum of phytopathogenic fungi, especially from the Ascomycetes and Basidiomycetes classes. Some of them have systemic activity and can be employed as leaf and soil fungicides.

They have particular importance for controlling a large number of fungi on various crop plants such as wheat, rye, barley, oats, rice, corn, grass, cotton, soybean, coffee, sugar cane, grapevines, fruit and S. 20 ornamental plants and vegetable crops such as cucumbers, beans and gourds, as well as the seeds of these plants.

The compounds are applied by treating the fungi or the seeds, plants, materials or soil to be protected from fungal attack with a fungicidally effective amount of the active ingredients. Application takes place before or after infection of the materials, plants or seeds by •the fungi.

The compounds are suitable for controlling the following specific plant diseases: 00 30 Erysiphe graminis (powdery mildew) on cereals, Erysiphe cichoracearum and Sphaerotheca fuliginea on gourds, Podosphaera leucotricha on apples, Uncinula necator on grapevines, Puccinia species on cereals, Rhizoctonia species on cotton and lawns, Ustilago species on cereals and sugar cane, 33 O.Z. 0050/41835 Venturia inaequal~ (scab) on apples, Helminthosporium species on cereals, Septoria nodorum on wheat, Botrytis cinerea (gray mold) on strawberries and grapevines, Cercospora arachidicola on peanuts, Pseudocercosporella herpotrichoides on wheat and barley, Pyricularia oryzae on rice, Phytophthora infestans on potatoes and tomatoes, Fusarium and Verticillium species on various crops, Plasmopara viticola on grapevines, Alternaria species on vegetables and fruit.

The novel compounds can also be used to protect materials (wood), eg. against Paecilomyces variotii.

The fungicidal agents generally contain from 0.1 to 95, preferably from 0.5 to 90, by weight of active ingredient.

The application rates depend on the nature of the

O*

desired effect and are from 0.02 to 3 kg of active 20 ingredient per ha.

Generally required for treating seeds is from 0.001 to 50 g, preferably 0.01 to 10 g, of active ingredient per kilogram of seeds.

The fungicidal agents according to the invention can contain other active ingredients, eg. herbicides, insecticides, growth regulators, fungicides or fertilizers. Mixing with fungicides in many cases results in an extension of the range of fungicidal activity.

Use Example Used for comparison was the active ingredient guazatine triacetate disclosed in GB 1 114 155.

Activity on downy mildew of grapevines o Leaves of pot grapevines of the MUller Thurgau variety were sprayed with an aqueous sprayable composition which contained 80% of active ingredient and 20% of emulsifier in dry matter. In order to be able to assess the duration of action of the active ingredients, the 34 O.Z. 0050/41835 plants were placed in'a greenhouse for 8 days after the spray deposit had dried. Only then were the leaves infected with a suspension of zoo spores of Plasmopara viticola (downy mildew of grapevines). The grapevines were then placed initially in a chamber saturated with water vapor at 24°C for 48 hours and then in a greenhouse at from 20 to 30°C for 5 days. After this time, the plants were placed in the humid chamber for a further 16 hours to increase the rate of sporangiophore discharge.

The extent of fungal attack was then assessed on the undersides of the leaves.

The result shows that active ingredients 12a, 14a, 30b and 31b when applied as a 0.025% strength (by weight) sprayable composition have a better fungicidal action than the known active ingredient A

I*

*I C

C.

I

*0

Claims

1. A substituted bisguanidine of the formula I R t-NH. 1 .(NH-(CH 2 n-X.-(CH 2) n-NH,- H-Rt R 2-N NIR 2 i V V V V V. V V V where R 1 and R 2 are each, independently of one another, hydro- gen.C 3 -C 1 0 -alkeflyl, C 3 -C 1 0 -alkynyl, C,-C 8 -alkoxy-C 2 C 8 -alkyl, C.-Cl.-haloalkenyl; or cycloalky. which has 5 12 carbon atoms in the ring and can carry up to three of the following substituents: hydroxyl, Cl-C 1 0 -alkyl, C 1 -Cl 0 alkoxcy, C-C 1 -haloalkyl and C 1 -C,-alkoxy-Cj-C.- alkyl; or benzyl which can be substituted up to three times by Cl-C 1 0 -alkyl or C 1 -Cl 0 -alkoxy, it being possible for the substituent also to carry a hydroxyl or Cl-C.-alkoxy group; or the benzyl is substituted by C,-C-haloalkyl, with the proviso that only one of R1 and R can be hydrogen; or Ri and R 2 are, together with the atoms which they substi- tute, a 5- to li-membered heterocyclic ring which can be substituted once to three times by C,-C 1 0 -alkyl or CI-Ce-alkoxy-C,-C.-alkyl; x is CH 2 0, a single bond, NH, N-(C 1 Cl 0 -alkyl) or N-benzyl whose phenyl. can be substituted once to three times by C,-C 1 -alkyl, Cl-C 1 -alkoxy, C,- C 1 0 -haloalkyl or halogen, and n is 5to 8, and its plant-compatible acid addition salts and its metal complexes.

2. A fungicide containing an effective amount of a bisguanidine of the formula I R I-NY H(CH 2 n-X- (CHz) n-NHN1+-R I R1-14 N1.R 2 N 0.Z. 0050/41835 SQ a.. a a Sea. *5 i a E ~.SS ~S S S iC a I, a a. ha a h a S S. as 9* I a a C a go 5*5* a a a eon *5 a 55 5' where RI and R 2 are each, independently of one another, hydro- ge i C 3 -C 1 -alkenyl, C 3 -Cia-alkynyl, C 1 ,-C-alkoxy-C,-C-alkyl, C 3 -C 1 -haloalkenyl; or cycloalkyl which has 5 12 carbon atoms in the ring and can carry up to three of the following substituents: hydroxyl, C, 1 -Cl.-alkyl, C 1 -C 10 alkoxy, C-C-haloalkyl and C,-C-alkoxy-C,-C 8 alkyl; or benzyl which can be substituted up to three times by C 1 -C 1 0 -alkyl o~r Cl-Cl 0 -alko-y, it being possible for the substituent also to carry a hydroxyl or C,,-C.-alkoxy group; or the benzyl is substituted by C,-C 1 0 -haloalkyl, with the proviso that only one of R' and R 2 can be hydrogen; or R1 and R 2 are, together with the atoms which they substi- tute, a 5- to il-membered heterocyclic ring which can be substituted once to three times by Cl-C 1 0 -alkyl or Cj-C.-alkoxy-C,-C 8 -alkyl; X is CH 2 0, a single bond, N1H, N-(Cl-CI 0 -alkyl) or N-benzyl whose phenyl can be substituted once to three times by C 1 -Cl 0 -alkyl, C,-C,.,-alkoxy, C 1 C 1 -haloalkyl or halogen, and n is 5to 8, or its plant-compatible salt or its metal complex and a liquid or solid carrier.

3. A process for controlling fungi, which comprises allowing an effective amount of a bisguanidine of the formula I R -NI NH-( CH 2 CH 2 n-NH- 1 .(NH-RI R2-,N N-R Z where R1 and Rz arr sach, independently of one another, hydro- ge., Pii. C3-C 1 0 -alkenyl, C 3 -Cl.-alkynyl, -o 0! ~VT oS' 0.Z. 0050/41835 Cl-C-alkoxy-C 2 -C-alkyl, C 3 -Cl 0 -ha loalkenyl; or cycloalkyl which has 5 12 carbon atoms in the ring and can carry up to three of the following substituents: hydroxyl, C 1 -C 10 -al kyl, C1-C 10 alkoxy, C,-C 1 0 -haloalkyl and Cl-C.-alkoxy-Cl-C.- alkyl; or benzyl which can be substituted up to three times by Cl-C 1 -alkyl or Cl-C 1 -alkoxy, it being possible for the substituent also to carry a hydroxyl or Cl-C 6 -alkoxy group; or the benzyl is subF tituted by C-C-haloalkyif with the proviso that only one of R1 and R 2 can be hydrogen; or R 1 and R 2 are, together with the atoms which they substi- tute, a 5- to li-membered heterocyclic ring which can be substituted once to three times by Cl-Cl-alkyl or C,-C-alkoxy-C-C-alkyl; X is CH 2 0, a single bond, NH, N-(Cl-Cl-alkyl) or N-benzyl whose phenyl can be substituted once to three times by Cl-C-alkyl, Cl-Cl.-alkoxy, Cj- C 1 -haloalkyl or halogen, and toevn is 5to 8, or its salt or metal complex to act on fungi, plants at risk of fungal attack, their habitat or t-heir seed, or on materials.

4. 1,13-Bis(3,3-dimethylcyclohexylguanidino)-7- azatridecane dihydroiodide. 1, 17-Bis cyclohexylguanidino-9-azaheptadecane see triacetate.

6. 1,13-Bis(N,N'-dicyclohexylguanidino)-7-azatri- &case:decane trihycirochloride.

7. 1, 12-Bis(2-axnino-3,4,5,6-tetrahydropyrimidyl) dodecane diacetate. DATED THIS 20th day of August, 1991 BASF AKTIENGESELLSCHAFT' WATEEM4ARK PATENT TRADEMARK ATTORNEYS, 2nd Floor, The Atrium, 290 Burwood Road, HAWTHORN. VICTORIA 3122.