Biocidal compounds their preparation and use

A phenylazoxycyanide compound of formula I ##STR1## is useful as an antimicrobial and fungicidal composition. A method for using the antimicrobial and fungicidal compositions, and for manufacturing the compound is also disclosed.

This application claims priority from copending provisional application 
Ser. No. 60/019979 filed on Jun. 17, 1996. 
BACKGROUND OF THE INVENTION 
Plant cultivation in agriculture and in horticulture is often threatened 
and damaged by pests and disease, such as disease caused by a variety of 
phytopathogenic fungi. To shield foods, crops and ornamental plants from 
fungal disease and to control such disease, many types of fungicides have 
been suggested. Phytopathogenic fungi often develop resistance to certain 
fungicidal agents after several years of application. Therefore, there is 
a permanent demand for new highly effective fungicides. 
Various fungicidal compounds with considerable activity against 
phytopathogenic fungi have been found to cause phytotoxic damage when 
applied to the plants at disease control rates. 
The prior art includes amidosulphonylphenylazoxycyanides of formula (A) 
##STR2## 
wherein Q represents a hydrogen or halogen atom and each of R.sub.1 and 
R.sub.2 independently represents a hydrogen atom, an optionally 
substituted phenyl or alkyl group or together may represent an alkylene 
chain which is optionally interrupted by an oxygen atom. These compounds 
are effective against a broad spectrum of phytopathogenic fungi. However, 
they are not completely satisfactory as fungicidal agents because of 
phytotoxic properties which may appear in unfavourable circumstances. 
Therefore, it is an object of this invention to provide a method for 
controlling undesired fungi without causing phytotoxic injury. 
It is another object of this invention to provide a fungicidal composition 
with little or no phytotoxic properties. 
It is a further object of this invention to provide arylazoxycanide 
compounds useful as non-phytotoxic fungicidal compounds. 
These and other objects and features of the invention will become more 
apparent from the detailed description set forth hereinbelow. 
SUMMARY OF THE INVENTION 
The present invention provides highly effective fungicidal 
phenylazoxycyanides of formula I which do not cause phytotoxic damage to 
the host plants when applied at disease control rates. Said 
phenylazoxycyanides are compounds of formula (I) 
##STR3## 
wherein R.sub.1 represents a hydrogen atom or a C.sub.1 -C.sub.4 alkyl 
group; 
R.sub.2 represents a C.sub.3 -C.sub.8 cycloalkyl group, which may be 
substituted by one to three C.sub.1 -C.sub.6 alkyl groups or may be 
condensed with a benzene or a cyclohexane ring; and 
X represents a hydrogen, fluorine, chlorine or bromine atom or a C.sub.1 
-C.sub.6 alkyl group. Said formula I compounds show excellent 
antimicrobial, particularly fungicidal, activity combined with low, 
uncritical phytotoxicity. 
Also provided are methods and compositions useful for non-phytotoxic 
control of phytopathogenic fungi. 
Specific embodiments of the invention are as follows: 
1. A compound comprising formula (I): 
##STR4## 
wherein R.sub.1 represents a hydrogen atom or a C.sub.1 -C.sub.4 alkyl 
group; 
R.sub.2 represents a C.sub.3 -C.sub.8 cycloalkyl group, which may be 
substituted by one to three C.sub.1 -C.sub.6 alkyl groups or may be 
condensed with a benzene or a cyclohexane ring; and 
X represents a hydrogen, fluorine, chlorine or bromine atom or a C.sub.1 
-C.sub.6 alkyl group. 
2. The compound of embodiment 1, wherein X represents a hydrogen atom. 
3. The compound of embodiment 1, wherein R.sub.1 represents a hydrogen 
atom. 
4. The compound of embodiment 1, wherein R.sub.1 and X each represent a 
hydrogen atom. 
5. The compound of embodiment 4, selected from the group consisting of 
4-(N-cyclopropylamidosulphonyl)phenylazoxycyanide; 
4-(N-cyclobutylamidosulphonyl)phenylazoxycyanide; 
4-(N-cyclopentylamidosulphonyl)phenylazoxycyanide; 
4-(N-cyclohexylamidosulphonyl)phenylazoxycyanide; 
4-(N-cycloheptylamidosulphonyl)phenylazoxycyanide; 
4-(N-cyclooctylamidosulphonyl)phenylazoxycyanide; 
4-(N-4-methylcyclohexylamidosulphonyl)phenylazoxycyanide; 
4-(N-1-tetralineamidosulphonyl)phenylazoxycyanide; and 
4-(N-methyl-N-cyclohexylamidosulphonyl)phenylazoxycyanide. 
6. A compound comprising formula Ia: 
##STR5## 
wherein R.sub.1 represents a hydrogen atom or a C.sub.1 -C.sub.4 alkyl 
group; and 
R.sub.2 represents a C.sub.3 -C.sub.8 cycloalkyl group, which may be 
substituted by one to three C.sub.1 -C.sub.6 alkyl groups or may be 
condensed with a benzene or a cyclohexane ring. 
7. An antimicrobial composition of embodiment 1, having an antimicrobially 
effective amount of the composition of formula I. 
8. The antimicrobial composition of embodiment 7, wherein X represents a 
hydrogen atom. 
9. A fungicidal composition of embodiment 1 having a fungicidally effective 
amount of the composition of formula I and an agriculturally acceptable 
carrier. 
10. The fungicidal composition of embodiment 9, wherein X represents a 
hydrogen atom. 
11. The fungicidal composition of embodiment 9, wherein R.sub.1 represents 
a hydrogen atom. 
12. The fungicidal composition of embodiment 9, wherein R.sub.1 and X each 
represent a hydrogen atom. 
13. The fungicidal composition of claim 12 selected from the group 
consisting of 
4-(N-cyclopropylamidosulphonyl)phenylazoxycyanide; 
4-(N-cyclobutylamidosulphonyl)phenylazoxycyanide; 
4-(N-cyclopentylamidosulphonyl)phenylazoxycyanide; 
4-(N-cyclohexylamidosulphonyl)phenylazoxycyanide; 
4-(N-cycloheptylamidosulphonyl)phenylazoxycyanide; 
4-(N-cyclooctylamidosulphonyl)phenylazoxycyanide; 
4-(N-4-methylcyclohexylamidosulphonyl)phenylazoxycyanide; 
4-(N-1-tetralineamidosulphonyl)phenylazoxycyanide; and 
4-(N-methyl-N-cyclohexylamidosulphonyl)phenylazoxycyanide. 
14. A fungicidal composition of embodiment 6 having a fungicidally 
effective amount of the compound of formula Ia. 
15. A method for combating an undesired microorganism, which comprises 
treating a locus infected therewith with the antimicrobial composition of 
embodiment 7. 
16. A method for combating a phytopathogenic fungi, which method comprises 
contacting the phytopathogenic fungi with a fungicidally effective amount 
of the composition of embodiment 9. 
17. The method according to embodiment 16 wherein R.sub.1 and X each 
represent a hydrogen atom. 
18. A process for the preparation of a compound of formula I 
##STR6## 
wherein R.sub.1 represents a hydrogen atom or a C.sub.1 -C.sub.4 alkyl 
group; R.sub.2 represents a C.sub.3 -C.sub.8 cycloalkyl group, which may 
be substituted by one to three C.sub.1 -C.sub.6 alkyl groups or may be 
condensed with a benzene or a cyclohexane ring; and X represents a 
hydrogen, fluorine, chlorine or bromine atom or a C.sub.1 -C.sub.6 alkyl 
group, the process comprising 
treating a nitroso compound of formula II 
##STR7## 
with N-bromosuccinimide and with sodium cyanamide. 
DETAILED DESCRIPTION OF THE INVENTION 
It has now been found that formula (I) phenylazoxycyanides 
##STR8## 
wherein R.sub.1 represents a hydrogen atom or a C.sub.1 -C.sub.4 alkyl 
group; 
R.sub.2 represents a C.sub.3 -C.sub.8 gcycloalkyl group, which may be 
substituted by one to three C.sub.1 -C.sub.6 alkyl groups or may be 
condensed with a benzene or a cyclohexane ring; and 
X represents a hydrogen, fluorine, chlorine or bromine atom or a C.sub.1 
-C.sub.6 alkyl group demonstrate an excellent antimicrobial, particularly 
fungicidal, activity combined with low, in practice, uncritical 
phytotoxicity. 
Within the above definitions, the alkyl groups may be straight or branched 
and the number of carbon atoms contained therein is preferably up to 4. 
The cycloalkyl groups represented by R.sub.2 may contain as substituents 
1, 2 or 3 alkyl groups, preferably methyl or ethyl groups. If two or more 
alkyl groups are present in a compound of formula I, the number of carbon 
atoms therein is independent from each other. 
X is preferably a hydrogen atom, a methyl or ethyl group or a fluorine or 
chlorine atom. Most preferred are compounds of formula I wherein X is a 
hydrogen atom. The amidosulphonyl group is preferably in the 4-position 
relative to the azoxycyanide moiety. 
The azoxycyanide group can exist in several isoelectronic forms; the 
formula for the azoxycyanide moiety used in the formulae in this 
application shall cover any such forms and the various formulae shall also 
cover any other types of isomers. 
A preferred group of compounds of formula I are those represented by 
formula Ia 
##STR9## 
wherein R.sub.1 and R.sub.2 are defined hereinabove for formula I. 
Typical compounds according to the invention include, but are not limited 
to: 
4-(N-cyclopropylamidosulphonyl)phenylazoxycyanide; 
4-(N-cyclobutylamidosulphonyl)phenylazoxycyanide; 
4-(N-cyclopentylamidosulphonyl)phenylazoxycyanide; 
4-(N-cyclohexylamidosulphonyl)phenylazoxycyanide; 
4-(N-cycloheptylamidosulphonyl)phenylazoxycyanide; 
4-(N-cyclooctylamidosulphonyl)phenylazoxycyanide; 
4-(N-4-methylcyclohexylamidosulphonyl)phenylazoxycyanide; 
4-(N-1-tetralineamidosulphonyl)phenylazoxycyanide; 
4-(N-methyl-N-cyclohexylamidosulphonyl)phenylazoxycyanide; and the like. 
Compounds of the invention may be prepared according to known methods such 
as those described in U.S. Pat. No. 5,475,093, which is incorporated 
herein by reference. Suitable starting materials are nitroso compounds of 
formula II 
##STR10## 
which may be converted to the corresponding azoxycyanide by reacting said 
formula II compound with N-bromosuccinimide in a polar solvent, such as 
dimethylformamide, preferably at ambient temperatures, subsequently 
treating the reaction mixture slowly with sodium cyanamide with stirring 
at ambient temperatures, diluting the resultant mixture with water, and 
isolating the desired azoxycyanide product by standard procedures such as 
extraction or filtration. 
The formula II nitroso compound starting material may be prepared according 
to known methods such as those described in published European patent 
application 411,720, which is incorporated herein by reference. For 
example, starting from the corresponding nitro compound the nitro group 
may be reduced by means of hydrazine hydrate in the presence of a catalyst 
such as rhodium/carbon and a solvent. The resultant hydroxylamine product 
may then be oxidised, e.g. with FeCl.sub.3, to give the nitroso compound 
of formula II. 
The phenylazoxcyanide compounds of the invention are particularly useful 
for combating or controlling a wide spectrum of phytopathogenic fungi, 
such as Plasmopara viticola, Botrytis cinerea, Alternaria solani, 
Phytophthora infestans, Venturia inaequalis, Leptosphaeria nodorum, and 
the like. Thus the compounds can be used for the treatment of plant 
diseases caused by said fungi in many plant cultures e.g. in vine, apples, 
tomatoes, potatoes, cereal crops, and the like. 
Therefore, there is provided a method of combating phytopathogenic fungi 
which comprises treating the fungi or the locus thereof with a 
fungicidally effective amount of a compound of formula I. The locus may be 
an agricultural or horticultural locus, for example plants, plant seeds or 
the medium in which said plants or seeds are growing or are to be grown or 
are stored. 
In actual practice, fungicidally effective amounts will vary according to 
the prevailing conditions such as the nature of the disease, degree of 
infection, plant species, plant size, mode of application, weather, soil 
and the like. A locus described above may suitably be treated with a 
compound of formula I at an application rate of about 0.04 kg/ha to 4.0 
kg/ha, preferably about 0.1 kg/ha to 1.0 kg/ha. 
The present invention further provides a biocidal, particularly fungicidal, 
composition which comprises a fungicidally effective amount of a compound 
of formula I or Ia as defined hereinabove and an agriculturally acceptable 
carrier. The composition of the invention may contain one or more 
compounds of formulae I or Ia. Preferably, at least one carrier in a 
composition according to the invention is a surface-active agent. For 
example, the composition may contain at least two carriers, at least one 
of which is a surface-active agent. 
The compounds according to formula I or Ia may also be applied directly as 
technical material, however, said compounds are preferably applied as a 
composition comprising, besides the formula I or Ia compounds, adjuvants 
and auxiliaries which are known for formulation purposes. Said 
compositions may be formulated as emulsion concentrates, trates, solutions 
which may be sprayed directly or diluted, luted, diluted emulsions, 
wettable powders, soluble powders, dusts, granulates, microencapsulates 
and the like. The form of application such as spraying, atomizing, 
dispersing, pouring, and the like may be chosen, like the compositions, 
according to the desired objectives and the given circumstances. 
It is contemplated, compounds of formula I or Ia may be formulated or 
applied, either alone or in combination, with one or more pesticides or 
plant growth regulants. Pesticides used in combination may be 
insecticides, acaricides or other fungicides or a combination thereof. 
When the formula I or Ia compounds are applied in combination with another 
pesticide or pesticides, they may be applied simultaneously or 
sequentially. Among the available fungicides which may be used in 
combination with the formula I compounds of the invention are 
4,6-dinitro-o-cresol, benalaxyl, benomyl, captafol, captan, carbendazim, 
chlorothalonil, copper, cymoxanil, dichlofluanid, dichlone, 
difenoconazole, dimethomorph, diniconzole, dinocap, dithianon, 
fenpiclonil, fenpropiomorph, hymaxazol, imazalil, iprodione, 
isoprothiolane, kasugamycin, mancozeb, mepronil, mercuric oxide, oxadixyl, 
oxolinic acid, penconazole, propineb, pyrifenox, thiabendazole, thiram, 
tolclofos-methyl, triadimefon, triflumizole, triforine validamycin A, 
vinclozolin, zineb, ziram, and the like. 
The fungicidal compositions of the invention may be prepared by 
well-established procedures, e.g. intensive mixing and/or grinding of the 
active ingredients with other substances, such as fillers, solvents, solid 
carriers, and optionally surface-active compounds (tensides). 
Solvents may be aromatic hydrocarbons, preferably the fractions C.sub.8 to 
C.sub.12, e.g. xylenes or xylene mixtures, substituted naphthalenes, 
phthalic acid esters, such as dibutyl or dioctyl phthalate, aliphatic 
hydrocarbons, e.g. cyclohexane or paraffins, alcohols and glycols as well 
as their ethers and esters, e.g. ethanol, ethyleneglycol mono- and 
dimethyl ether, ketones such as cyclohexanone, strongly polar solvents 
such as N-methyl 2-pyrrolidone, dimethyl sulphoxide, alkyl formamides, 
epoxidized vegetable oils, e.g. epoxidized coconut or soybean oil, water 
and the like. 
Solid carriers, which may be used for dusts or dispersible powders, may be 
mineral fillers, such as calcite, talc, kaolin, montmorillonite, 
attapulgite. The physical properties may be improved by addition of highly 
dispersed silica gel or highly dispersed polymers. 
Solid carriers for granulates may be porous material, e.g. pumice, broken 
brick, sepiolite, bentonite, non-sorptive carriers may be calcite or sand 
and the like. Additionally, a multitude of pre-granulated inorganic or 
organic materials may be used, such as dolomite or crushed plant residues. 
Suitable surface-active substances may be nonionogenic, anionic or cationic 
tensides with good dispersing, emulgating and wetting properties depending 
on the nature of the azoxycyanide compound to be formulated. Tensides may 
also mean mixtures of tensides. 
Suitable tensides may be so-called water-soluble soaps as well as 
water-soluble synthetic surface-active compounds. Soaps usually are 
alkali, earth alkali or optionally substituted ammonium salts of higher 
fatty acids (C.sub.10 -C.sub.20), e.g. the sodium or potassium salts of 
oleic or stearic acid or of mixtures of natural fatty acids which are 
prepared, for example, from coconut or tallow oil. Furthermore, 
methyl-taurine salts of fatty acids may be used. However, so-called 
synthetic tensides are preferably used, especially fatty sulphonates, 
fatty sulphates, sulphqnated benzimidazole derivatives or alkyl aryl 
sulphonates. The fatty sulphates or fatty sulphonates onates are normally 
used as alkali, earth alkali or optionally substituted ammonium salts and 
have an alkyl moiety of 8 to 22 carbon atoms, whereby alkyl also means the 
alkyl moiety of acyl residues, such as the sodium or calcium salt of 
lignin sulphonic acid, of sulphuric acid dodecylate or of a mixture of 
fatty alcohols prepared from natural fatty acids. This also includes the 
salts of sulphuric acid esters, sulphonic acids and adducts of fatty 
alcohols and ethylene oxide. The sulphonated benzimidazole derivatives 
preferably contain 2 sulphonic acid residues and a fatty acid residue with 
8 to 22 carbon atoms. Alkyl aryl sulphonates are, for example, the sodium, 
calcium or triethyl ammonium salts of dodecyl benzene sulphonic acid, 
dibutyl naphthalene sulphonic acid or of a condensate of naphthalene 
sulphonic acid and formaldehyde. Furthermore, phosphates, such as the 
salts of the phosphoric acid ester of a p-nonylphenol-(4-14)-ethylene 
oxide adduct or phospholipids, may be used. 
Non-ionic tensides are preferably polyglycolether derivatives of aliphatic 
or cycloaliphatic alcohols, saturated or non-saturated fatty acids and 
alkylphenols, which have 3 to 10 glycol ether groups and 8 to 20 carbon 
atoms in the (aliphatic) hydrocarbon residue and 6 to 18 carbon atoms in 
the alkyl residue of the alkyl phenols. Other suitable non-ionic tensides 
are the water-soluble, 20 to 250 ethylene glycol ether groups containing 
polyadducts of ethylene oxide and polypropylene glycol, ethylene diamino 
polypropylene glycol and alkyl polypropylene glycol with 1 to 10 carbon 
atoms in the alkyl moiety, the substances normally contain 1 to 5 ethylene 
glycol units per propylene glycol unit. Examples of non-ionic tensides are 
nonylphenol polyethoxy ethanols, castor oil polyglycol ether, polyadducts 
of ethylene oxide and polypropylene, tributyl phenoxy polyethoxy ethanol, 
polyethylene glycol, octyl phenoxy polyethoxy ethanol. Furthermore, fatty 
acid esters of polyoxy ethylene sorbitan, such as polyoxy ethylene 
sorbitan trioleate may be used. 
Cationic tensides preferably are quaternary ammonium salts, which have at 
least one alkyl residue with 8 to 22 carbon atoms and, furthermore, low, 
optionally-halogenated alkyl, benzyl or hydroxyalkyl residues. The salts 
are preferably halides, methyl sulphates or alkyl sulphates, e.g. stearyl 
trimethyl ammonium chloride or benzyl bis(2-chloroethyl) ethyl ammonium 
bromide. 
The tensides generally used for compositions of the invention are disclosed 
in publications such as: 
"McCutheon's Detergents and Emulsifiers Annual", MC Publishing Corp., 
Ridgewood, N.J., USA 1981; 
H. Stache, "Tensid-Taschenbuch", 2nd ed., C. Hanser, Munich, Vienna, 1981; 
M. and J. Ash, "Encyclopedia of Surfactants", vol. I-III, 
Chemical Publishing Co., New York, NY, USA 1980-1981. 
The pesticidal compositions of the invention may comprise 0.1% to 95%, 
preferably 0.1% to 80% of at least one compound of formula I or Ia, 1% to 
99.9% of a solid or liquid adjuvant and 0% to 25%, preferably 0.1% to 25%, 
of a tenside. 
Examples of the compositions of the invention are: 
Emulsion Concentrates: 
Active ingredient: 1% to 20%, preferably 5% to 10% Surface-active 
substance: 5% to 30%, preferably 10% to 20% 
Liquid carrier: 50% to 94%, preferably 70% to 85% 
Suspension-Concentrates: 
Active ingredient: 5% to 75%, preferably 10% to 50% 
Water: 94% to 24%, preferably 88% to 30% 
Surface-active substance: 1% to 40%, preferably 2% to 30% 
Wettable Powder: 
Active ingredient: 0.5% to 90%, preferably 1% to 80% 
Surface-active substance: 0.5% to 20%, preferably 1% to 15% 
Solid carrier: 5% to 95%, preferably 15% to 90% 
Dusts: 
Active ingredient: 0.1% to 10%, preferably 0.1% to 1% 
Solid carrier: 99.9% to 90%, preferably 99.9% to 99% 
Granulates: 
Active ingredient: 0.5% to 30%, preferably 3% to 15% 
Solid carrier: 99.5% to 70%, preferably 97% to 85% 
As commodities the inventive fungicidal compositions may preferably be in a 
concentrated form whereas the end-user generally employs diluted 
compositions. Said compositions may be diluted to a concentration of 
0.001% of active ingredient (a.i.). The doses usually are in the range of 
about 0.01 to 10 kg a.i./ha. 
Said compositions may also comprise other auxiliaries such as stabilizers, 
defoamer, viscosity controlling agents, thickeners, adhesives, fertilisers 
or other active ingredients to obtain special effects. 
For a more clear understanding of the invention, the following specific 
examples are set forth below. These examples are merely illustrations and 
are not to be understood as limiting the scope and underlying principles 
of the invention in any way. Indeed, various modifications of the 
invention in addition to those shown and described herein will become 
apparent to those skilled in the art from the following examples and 
foregoing description. Such modifications are also intended to fall within 
the scope of the appended claims. The term 1H-NMR as used in the examples 
hereinbelow designates proton nuclear magnetic resonance.