1,2-Dialkyl-3(or 3,5)-N-heterocyclic pyrazolium salts or derivatives thereof as fungicidal agents

There is provided a method for controlling fungi with a fungicidally effective amount of a 1,2-dialkyl-3(or 3,5)-N-heterocyclic pyrazolium salt. There is also provided a method for protecting living plants from attack by fungi through the application to the foliage of said plants of a fungicidally effective amount of such pyrazolium salt compounds.

The present invention relates to a method for controlling fungi with 
pyrazolium compounds which have a nitrogen containing heterocyclic group 
either in the 3 position, or in the 5 position or in the 3 and 5 positions 
of the pyrazolium ring and are represented by a formula: 
##STR1## 
wherein R.sub.3 is a member selected from the group consisting of 
hydrogen, methyl, hydroxy and phenyl; R.sub.4 represents a member selected 
from the group consisting of hydrogen or halogen; R.sub.5 represents a 
member selected from the group consisting of phenyl, cyclohexyl and 
##STR2## 
X represents an anion with a charge of 1 or 2 and preferably 1; n 
represents an integer selected from 4, 5 and 6; m represents an integer 
selected from 1 and 2; and HB represents an inorganic or organic acid. 
As employed in the present application the term "halogen" is intended to 
mean fluorine, chlorine, bromine and iodine; however, bromine is 
preferred. 
Illustrative of the anions, represented by X, which are suitable for use in 
the present invention are, for example, halides such as chloride, bromide 
or iodide; acetate; sulfate, hydroxide; hydrogen sulfate; methyl sulfate; 
benzene sulfonate; alkoxy (C.sub.1 -C.sub.4) benzene sulfonate: alkyl 
(C.sub.1 -C.sub.3) benzene sulfonate, such as, p-toluene sulfonate; 
nitrate; phosphate; tetrafluoroborate, (C.sub.6 H.sub.5).sub.4 B; iodate; 
alkane sulfonate (C.sub.1 -C.sub.4); perchlorate; Br.sub.3.sup.- and 
I.sub.3.sup.-. 
With regard to the pyrazolium salts of formula (I), it is to be understood 
that certain multivalent anions such as sulfate, phosphate, and the like 
may have associated with them a cation in addition to the pyrazolium, as 
for example a proton or an alkali metal or alkaline earth metal. For 
simplicity, such anions are characterized as being unionized, although 
they probably are further ionized in fact. Typical representations are: 
NaSO.sub.4.sup.-, KPO.sub.4.sup.=, MgPO.sub.4.sup.-, HSO.sub.4.sup.-, and 
NaHPO.sub.4.sup.-. 
Illustrative of the acid residue, identified in formula (II) above as 
.sup.. HB, which is suitable for use in the present invention are (a) 
inorganic acids, such as HCl, HI, HBr, HClO.sub.4, H.sub.2 SO.sub.4, 
HNO.sub.3 and H.sub.3 PO.sub.4 and (b) organic acids, such as CH.sub.3 
SO.sub.3 H, 
##STR3## 
ClCH.sub.2 COOH, and other organic acids of sufficient acid strength to 
form stable salts with 
##STR4## 
group. 
Preferred compounds useful for the practice of the method of this invention 
are represented by above-identified formulas (I) and (II), respectively, 
wherein R.sub.3 is hydrogen or methyl; R.sub.4 is hydrogen, R.sub.5 is 
phenyl, or cyclohexyl; n is 5; m is 1 or 2; and X is an anion with a 
charge of 1 or 2. 
Exemplary of the effective compounds useful in the present invention are: 
1,2-Dimethyl-3-phenyl-5-piperidinopyrazolium iodide, hydroiodide, 
1,2-Dimethyl-3-phenyl-5-piperidinopyrazolium perchlorate, perchloric acid 
salt, 
1,2-Dimethyl-3-phenyl-5-(1-pyrrolidinyl)pyrazolium methyl sulfate, 
3-(Hexahydro-1H-azepin-1-yl)-1,2-dimethyl-5-phenylpyrazolium iodide, 
1,2-Dimethyl-3-(4-methylpiperidino)-5-phenylpyrazolium iodide, 
1,2-Dimethyl-3-(2-methylpiperidino)-5-phenylpyrazolium iodide, 
1,2-Dimethyl-3-(3-methylpiperidino)-5-phenylpyrazolium iodide, 
4-Bromo-1,2-dimethyl-3,5-dipiperidinopyrazolium bromide, hydrobromide, 
4-Bromo-1,2-dimethyl-3,5-dipiperidinopyrazolium perchlorate, perchloric 
acid salt, 
1,2-Dimethyl-3,5-dipiperidinopyrazolium bromide, nitric acid salt, 
1,2-Dimethyl-3,5-dipiperidinopyrazolium perchlorate, 
1,2-Dimethyl-3-(3-methylpiperidino)-5-phenylpyrazolium perchlorate, 
1,2-Dimethyl-3-(3-methylpiperidino)-5-phenylpyrazolium bromide, 
1,2-Dimethyl-3-(3-methylpiperidino)-5-phenylpyrazolium methyl sulfate, 
1,2-Dimethyl-3-(3-piperidino)-5-phenylpyrazolium chloride, 
1,2-Dimethyl-3-(2-methylpiperidino)-5-phenylpyrazolium methyl sulfate, 
3-Cyclohexyl-1,2-dimethyl-5-(3-methylpiperidino)pyrazolium methyl sulfate 
(and chloride), 
1,2-Dimethyl-3-(2-methylpiperidino)-5-phenylpyrazolium perchlorate, 
1,2-Dimethyl-3-(2-methylpiperidino)-5-phenylpyrazolium chloride 
hydrochloride, 
3-Cyclohexyl-1,2-dimethyl-5-(3-methylpiperidino)pyrazolium iodide, 
3-Cyclohexyl-1,2-dimethyl-5-piperidinopyrazolium iodide, 
1,2-Dimethyl-3-(3-hydroxypiperidino)-5-phenylpyrazolium iodide, 
In accordance with the invention, compounds of formula (I) defined above 
can be synthesized from an intermediate (IV), defined below, by reaction 
of the intermediate 3-halopyrazolium compounds (IV) with a saturated 
azaheterocycle or a saturated N-containing heterocycle (III) 
herein-defined within a temperature range of from about 20.degree. C. to 
about 100.degree. C. In this reaction it is necessary to include either 
two moles of the azaheterocycle, one as a base acceptor, or to use one 
mole of azaheterocycle and one mole or an organic or inorganic base 
acceptor. In practice tertiary amines, such as trimethylamine, 
triethylamine, pyridine or quinoline as well as inorganic bases, such as 
sodium bicarbonate, sodium carbonate and the like can be employed. 
The reaction is graphically illustrated as "Method A" as follows: 
##STR5## 
where R.sub.3, R.sub.4, R.sub.5, m, n and X are each defined above. This 
reaction involves displacement of a halogen by a azahetero-cycle group. 
Additionally a variety of inert solvents such as methanol, ethanol, 
propanol, dimethylformamide (DMF), acetone, acetonitrile or the like can 
be utilized during reaction. 
A limitation to this procedure is reaction temperature and time. Heating 
the (IV) compound with an excess of azaheterocycle, especially at 
temperatures above 100.degree. C. over an extended time, causes increasing 
dealkylation of the pyrazolium compound (I) to the pyrazole. Thus, to 
prevent dealkylation, the preferred reaction temperature is 80.degree. C., 
or less, and preferably 40.degree. C. to 80.degree. C. 
The counter ion X employed in the Method A may be any of those listed, 
although methyl sulfate, iodide, bromide, chloride, perchlorate, and 
tetrafluoroborate are generally preferred. The product identified by 
formula (I) may be prepared with a particular anion X either by reacting 
compound IV containing the required anion X or by alternative procedures 
outlined below. For example, the anion of (I) may be replaced either by 
exchange chromatography (Method A) on an appropriately modified Dowex 1-X8 
base anion exchanged or in some cases by the addition of a concentrated 
solution of an acid salt (Method A salt) e.g. utilizing sodium iodide, 
sodium tetrafluoroborate, or sodium perchlorate [or 10% aqueous perchloric 
acid (Method A acid)], thereby causing the water insoluble salt to 
precipitate. When an acid is used as, for instance, perchloric acid, not 
only does ion exchange occur, but there also may occur the formation of a 
perchlorate salt of the azaheterocyclic group. 
Purification of a formula (I) compound above can be effected by dissolving 
said compound in water, excepting the water insoluble salts, such as 
perchlorate or iodide, and washing the aqueous layer with ether, 
discarding the ether layer, then extracting the same with chloroform or 
methylene chloride. Product (I) may then be precipitated from the 
chlorinated hydrocarbon by the addition of diethyl ether. 
The preparation of 3-halopyrazolium compound (IV) employed in Method A can 
be accomplished by the stepwise reactions involving: (1) a benzoyl acetic 
acid ester or a cycloalkanoyl acetic acid ester (V) defined more 
particularly hereinbelow with methyl hydrazine to yield a 3-pyrazolinones 
(VI), (2) halogenation of said pyrazolinone (VI) with phosphorus oxyhalide 
to yield the corresponding 3-halopyrazole (VII) and, (3) methylation of 
said 3-halopyrazole VII to yield a 3-halopyrazolium compound (IV). 
Conversion of the formula (IV) 3-halopyrazolum salt to the formula (I) 
pyrazolium salt containing, the 3-nitrogen heterocyclic group is readily 
achieved by reaction of the halopyrazolium salt with an azaheterocycle in 
the presence of base, as described above. 
The four reaction steps are graphically illustrated below with phosphorous 
oxychloride used to represent the oxyhalide employed as the halogenation 
reagent of the pyrazolinone (VI). 
##STR6## 
where R.sub.3, R.sub.4, R.sub.5, m and n are each as defined above. 
The methylation reaction in Step 3 above is preferably conducted in the 
presence of a solvent, such as xylene, toluene, benzene, 
1,2-dichloroethane or the like. Alternatively, it may be conducted to the 
exclusion of a solvent using solely the halopyrazole (VII) reactant and 
the alkylating agent. 
Illustrative methylation reagents include, methyl sulfate, methyl halides, 
methyl hydrogen sulfate, methyl toluene sulfonate and the like. 
In general, the halopyrazole and methylating reagent combine on an 
equimolar basis. However, it is a good practice to employ an excess of the 
methylating agent. Optimum reaction conditions for effecting the 
methylations will vary depending on the reactants employed. Reaction is 
effected by combining the methylating agent and an halopyrazole usually in 
the presence of a solvent. The reaction mixture is heated until the 
reaction occurs. Where the methylating reagents employed are volatile, 
such as methyl chloride, the reaction is preferably conducted in a sealed 
vessel under pressure, to avoid loss of the reactants. The quaternization 
of the formula (IV) 3-halopyrazolium compound is accomplished by utilizing 
a methylating agent, such as dimethylsulfate, methyl chloride, methyl 
iodide or other such agent, alone or admixed with a solvent. 
The preparation of formula (IV) 3-halopyrazolium compounds where R.sub.4 is 
halogen, can be accomplished by direct halogenation of the 
1-methyl-3-halopyrazole (VII) in acetic acid. 
Compounds containing 3,5-disubstituted azaheterocyclic substituents (IX) 
can be prepared by a process, hereinafter referred to as Method B. This 
method involves the reaction of a 3,5-dihalopyrazolium compound with an 
azaheterocycle; both 3 and 5-dihalogens react rapidly at ambient 
temperatures up to 80.degree. C. However, under these conditions, the 
substituent in the 4-position, even a 4-halogen, is unreactive to an 
azaheterocycle. The reaction is preferably conducted in the presence of a 
base and an aprotic solvent such as xylene, toluene, benzene or the like. 
This reaction "Method B" is graphically illustrated as follows: 
##STR7## 
where R.sub.3, R.sub.4, m and n are each as defined above. 
In practice it has been found that formula (X) 
3,5-diazaheterocyclylaminopyrazolium compounds where R.sub.4 is hydrogen, 
can be most advantageously prepared from formula (IX) 
3,5-diazeheterocyclylamino-4-halopyrazolium compounds by a 
dehydrohalogenation process, hereinafter referred to as "Method C." The 
process involves the reaction of a 
3,5-diazaheterocyclylamino-4-halopyrazolium salt (XI) with hydrogen, in 
the presence of a strong base such as an alkali metal alkoxide (e.g. 
sodium methoxide, sodium ethoxide or potassium t-butoxide) and a catalyst 
such as palladium or platinum on carbon. The reaction is preferably 
conducted at a temperature between about 20.degree. C. and 40.degree. C. 
and may be illustrated as follows: 
##STR8## 
As noted above, the hereinabove recited compounds are effective for the 
control of fungi which infect many living plants. They are particularly 
effective for controlling powdery mildew, especially on grains such as 
barley, corn, sorghum and wheat, on vines such as cucumbers, grapes and 
pumpkin and on fruit and nut trees such as apples, pears and pecans. 
However, they are also effective for controlling fungi which are the 
causative agents for other diseases such as rice blast, and apple scab. 
In utilizing the above-identified pyrazolium salts for protecting plants 
from pathogenic fungi, it has been found most advantageous to apply the 
compounds herein foliage of the plant in the form of a liquid, preferably 
aqueous, spray. Solutions or suspensions containing from about 100 to 5600 
ppm, and preferably 100 to 1000 ppm of the pyrazolium salt, are generally 
highly effective for this use. 
For application as liquid sprays, said compounds are generally prepared as 
emulsifiable concentrates, wettable powders, or water miscible 
concentrates which are diluted with water or other suitable polar 
solvents, and then applied as a dilute spray. Generally such sprays are 
applied at the volume rate of about 938 liters to 1877 liters/hectare 
(l/ha) or about 100 to 200 gal per acre. It is, of course, obvious that 
smaller or larger volumes of liquid spray may be employed, eg., 400 to 
4000 l/ha may be used depending on a variety of factors including the type 
of crop, the plant spacing and the amount of foliage per plant being 
treated. 
Wettable powder formulations can be prepared by grinding together about 25% 
to 95% by weight of the pyrazolium salt and about 75% to 5% by weight of a 
solid diluent such as attapulgite, kaolin, bentonite, diatomaceous earth, 
silica, talc, fullers earth or the like. To this mixture is added about 1% 
to 5% by weight of a dispersing agent, such as the calcium salt of a 
polymerized alkyl aryl sulfonic acid, sodium lignosulfonate, or sodium 
salt of condensed naphthalene sulfonic acid, and about 1% to 5% by weight 
of a surfactant, such as polyoxyethylated vegetable oil, alkyl phenoxy 
polyoxyethylene ethanol, sodium alkyl naphthalene sulfonate, is also 
blended with the formulation. 
The water-miscible concentrates are prepared by dissolving from 15% to 70% 
by weight of the compound in 85% to 30% by weight of a water-miscible 
solvent, such as water itself or another polar water-miscible solvent, 
such as 2-methoxy ethanol, methanol, propylene glycol, diethylene glycol, 
diethylene glycol monoethyl ether, formamide, and methylformamide. 
Application of the material is made by adding a predetermined quantity of 
the water-miscible concentrate to a spray tank and applying as such or in 
combination with additional suitable diluent, such as a further quantity 
of water or one of the above polar solvents mentioned above. 
The performance of the production the above formulations, which are applied 
as liquid sprays, is improved by adding a surfactant or blend of 
surfactants thereto. Conventional nonionic surfactants are preferred and 
the surfactants are preferably added to the formulation or the spray tank 
at the rate of 0.1% to 5% by volume to provide good wetting of the spray 
solution on plant foliage. 
Suitable nonionic surfactants include alkyl polyoxyethylene ethers, 
polyoxyethylene (20) sorbitan monolaurate, polyoxyethylene (20) sorbitan 
monooleate, alkylarylpolyglcol ethers, alkyl phenol ethoxylates, trimethyl 
nonyl polyethylene glycol ethers, alkyl phenol ethylene oxide condensates, 
octyl phenoxy polyethoxy ethanols, nonylphenyl polyethylene glycol ethers, 
condensates of polyoxy ethylenes, polyoxy propylenes, aliphatic 
polyethers, aliphatic polyesters, alkylarly poloxyethylene glycols, and 
the like. Especially preferred nonionic surfactants having a 
hydrophilic-lipophilic balance (HLB) of from 11 to 16. This conventional 
surfactant classification test is described, for example, at page 232 et 
seq. of Emulsion Theory and Practice by Paul Becker, Rheinholt Publishing 
Corporation, second edtion (1965); also available as No. 162 in the 
American Chemical Society's Monograph Series. 
Generally, the plants which are to protected against attack from fungal 
organisms are sprayed to run off with solutions or suspensions of the 
above-identified compounds. In practice it has been found that solutions 
or suspensions containing from about 100 to 5600 ppm of the compounds 
herein and preferably 100 to 1000 ppm of such compounds afforded the 
desired protection. 
In order to facilitate a further understanding of the invention, the 
following examples are presented primarily for purposes of illustrating 
certain more specific details thereof. The invention is not to be deemed 
limited thereby except as defined in the claims. Unless otherwise noted, 
the parts are by weight.

EXAMPLE 1 
To determine the effectiveness of the 1,2-dialkyl-3(or 3,5)-mono(or 
di)heterocyclic pyrazolium salts as fungicidal agents, a variety of 
pathogenic fungi, host plants and acid salts are used in the following 
tests. Pathogens, host plants, the method of testing, the rating system 
used, and the data obtained are set forth below. 
Pathogens: 
Piricularia oryzae Cavara, the rice blast pathogen. 
Venturia inaequalis (Cke.) Wint. which causes apple scab. 
Erysiphe cichoracearum DC, the cause of powdery mildew on cucurbits. 
Podosphaera leucotricha (E. & E.) Salm., the cause of powdery mildew of 
apples and pears. 
Erysiphe graminis f. sp. tritici the cause of powdery mildew on wheat. 
Erysiphe graminis f. sp. hordei the cause of powdery mildew on barley. 
Host Plants: 
Rice (Oryza sativa) Cv. Nato) 
Cucumber (Cucumis sativus) (Cv. Marketer) 
Apple (Malus sylvestris) (Seedling) 
Wheat (Triticum aestivum Cv. Bonanza) 
Barley (Hordeum vulgare Cv. Larker) 
Plants are individually grown in 5.08 cm peat squares and assembled in 7.62 
cm. .times. 25.4 pm. pressed fibre containers the week prior to spraying. 
With exception of rice, barley, and wheat, a single specimen of each 
species is used. A separate container is used for those plants in the 
mildew evaluation. The complete test system is shown below. 
______________________________________ 
Series 1 Series 2 
______________________________________ 
Rice: Rice Blast Apple: Powdery Mildew 
Apple: Apple Scab Cucumber: Powdery Mildew 
Wheat: Powdery Mildew 
Barley: Powdery Mildew 
______________________________________ 
Spray solutions are prepared at a final concentration of 100 ppm or 500 ppm 
in 50 ml of 50% aqueous acetone. Acetone is added to solubilize the test 
compound and solutions made to final volume with deionized water. 
Two containers, one each from Series 1 and 2 (see above), are sprayed 
simultaneously on a turntable with 50 ml of the test solution. Spray is 
provided by two fixed spraying nozzles mounted to deliver vertical and 
horizontal solid cone spray patterns. Immediately thereafter, all plants 
are returned to the greenhouse to permit the deposit to dry. Plants of 
Series 1 and 2 are separately inoculated. Plants in Series 1 are 
inoculated with conidial suspensions of the respective pathogens using a 
paint sprayer operated under 4-6 psig and, immediately, are transferred to 
a controlled temperature/humidity cabinet (ambient temperature, RH-95%). 
Plants in Series 2 are dusted with respective powdery mildew conidia and 
then removed to the controlled environment plant culture room (10 hours 
light, .about.22.degree. C., RH45%) to await disease development. Plants 
in Series 1 are held 4 days in the cabinet then transferred to the 
greenhouse to await disease expression. 
PERFORMANCE RATING 
All plants are rated for disease severity on a scale of 1 to 7 (clean to 
kill), as described below: 
______________________________________ 
Rating Description 
______________________________________ 
1 Clean 
2 Trace disease 
3 Slight disease 
4 Moderate disease 
5 Heavy disease 
6 Severe disease 
7 Kill 
______________________________________ 
In the tables hereinbelow presented, the numerical rating is used for 
clarity. Data obtained are reported in Tables I and II below. The ratings 
reported represent data obtained from one or more individual tests. Where 
more than one test has been conducted, the ratings are averaged and 
reported as a single value rating. For each table, there is also provided 
a rating value for the checks employed and a rating range for acceptable 
disease control. It is, of course, obvious that the lower the value, the 
more effective the disease control. 
Table I 
__________________________________________________________________________ 
Disease Severity of Plants Sprayed to Run-off 
with Indicated Rates (ppm) 
__________________________________________________________________________ 
Rice Blast 
Apple Scab 
Compound 500 
100 500 100 
__________________________________________________________________________ 
Acceptable Level of Control 
1-4 1-4 
Untreated Controls Average Rating 
5.1 5.4 
__________________________________________________________________________ 
1,2-Dimethyl-3-phenyl-5-piperidino- 
3.0 
pyrazolium iodide 
1,2-Dimethyl-3-phenyl-5-(1-pyrrolidinyl)- 
4.0 
pyrazolium methyl sulfate 
1,2-Dimethyl-3-(4-methylpiperidino)-5- 
4.0 
phenylprazolium iodide 
1,2-Dimethyl-3-(3-methylpiperidino)-5- 
4.0 
phenylpyrazolium bromide 
1,2-Dimethyl-3-(3-methylpiperidino)-5- 
3.5 
phenylpyrazolium perchlorate 
1,2-Dimethyl-3-(3-methylpiperidino)-5- 
4.0 
phenylpyrazolium methyl sulfate 
1,2-Dimethyl-3-(3-methylpiperidino)-5- 
3.0 4.0 
phenylpyrazolium chloride 
1,2-Dimethyl-3-(2-methylpiperidino)-5- 
4.0 
phenylpyrazolium perchlorate 
3-Cyclohexyl-1,2-dimethyl-5-(3-methyl- 
piperidino)pyrazolium methyl sulfate 
(and chloride) 
3-Cyclohexyl-1,2-dimethyl-5-(3-methyl- 
2.0 3.0 
piperidino)pyrazolium iodide 
3-Cyclohexyl-1,2-dimethyl-5-piperidino- 
4.0 2.0 3.0 
pyrazolium iodide 
4-Bromo-1,2-dimethyl-5-(3-methyl- 3.0 
piperidino)-3-phenylprazolium iodide 
4-Bromo-1,2-dimethyl-5-(4-methyl- 
2.0 3.0 
piperidino)-3-phenylpyrazolium iodide 
4-bromo-1,2-dimethyl-3-phenyl-5- 
4.0 4.0 
Piperidino-pyrazolium iodide 
4-Bromo-1,2-dimethyl-3-(2-methylpiperi- 
1.0 
dino)-5-phenylpyrazolium perchlorate 
3-(3-Hydroxypiperidino)-1,2-dimethyl-5- 
1.0 
phenylpyrazolium perchlorate 
__________________________________________________________________________ 
Table II 
__________________________________________________________________________ 
Disease Severity of Plants Sprayed to Run-off with Indicated Rates 
__________________________________________________________________________ 
(ppm) 
Cucumber 
Wheat Apple Barley 
Powdery 
Powdery 
Powdery 
Powdery 
Compound 500 
100 500 
100 500 
100 500 
100 
__________________________________________________________________________ 
Acceptable Level of Control 
1-4 1-3 1-3 1-4 
Untreated Controls Average Rating 
6.0 5.9 5.6 5.4 
__________________________________________________________________________ 
1,2-Dimethyl-3-phenyl-5-piperidino- 
4.0 2.3 
3.0 3.3 
3.5 4.0 
4.0 
pyrazolium iodide 
3-(Hexahydro-1H-azepin-1-yl)-1,2- 
4.0 3.0 4.0 
dimethyl-5-phenylpyrazolium iodide 
1,2-Dimethyl-3-(4-methylpiperidino)- 
1.0 2.0 3.0 
5-phenylpyrazolium iodide 
1,2-Dimethyl-3-(2-methylpiperidino)- 
2.8 3.3 
4.3 
5-phenylpyrazolium iodide 
1,2-Dimethyl-3-(3-methylpiperidino)- 
1.0 
4.0 3.0 1.0 
3.0 
5-phenylpyrazolium iodide 
1,2-Dimethyl-3-(3-methylpiperidino)- 
2.7 2.0 
2.5 3.3 
2.5 2.5 
4.0 
5-phenylpyrazolium bromide 
1,2-Dimethyl-3-(3-methylpiperidino)- 
4.3 2.3 4.3 3.5 
5-phenylpyrazolium perchlorate 
1,2-Dimethyl-3-(3-methylpiperidino)- 
3.0 4.0 
5-phenylpyrazolium methyl sulfate 
1,2-Dimethyl-3-(3-methylpiperidino)- 
1.0 1.0 
5-phenylpyrazolium chloride 
1,2-Dimethyl-3-(2-methylpiperidino)- 
3.3 4.0 3.5 
5-phenylpyrazolium chloride hydro- 
chloride 
1,2-Dimethyl-3-(2-methylpiperidino)- 
4.0 4.0 
5-phenylpyrazolium perchlorate 
1,2-Dimethyl-3-(2-methylpiperidino)- 
4.0 
5-phenylpyrazolium methyl sulfate 
3-Cyclohexyl-1,2-dimethyl-5-(3- 
4.0 1.0 
3.0 3.0 2.0 
4.0 
methylpiperidino)pyrazolium methyl 
sulfate and chloride 
3-Cyclohexyl-1,2-dimethyl-5-(3- 
1.0 
4.0 2.0 
4.0 4.0 3.0 
4.0 
methylpiperidino)pyrazolium iodide 
3-Cyclohexyl-1,2-dimetyl-5-piper- 
1.0 2.0 
4.0 
idinopyrazolium iodide 
4-Bromo-1,2-dimethyl-5-(3-methyl- 
2.0 
3.0 2.0 
3.0 
piperidino)-3-phenylpyrazolium 
iodide 
4-Bromo-1,2-dimethyl-3-phenyl-5- 
3.0 
4.0 4.0 4.0 
piperidinopyrazolium iodide 
__________________________________________________________________________ 
EXAMPLE 2 
The fungicidal activity of the compounds of the present invention is 
demonstrated in the following tests. 
Wheat plants are individually grown in 5.08 cm peat squares and assembled 
in containers the week prior to spraying. 
Spray solutions are prepared at a final concentration of 500 ppm in 50%/50% 
water/acetone mixtures. The plants are placed on a turntable and sprayed 
with 50 ml of test solution. Immediately thereafter they are placed on 
greenhouse benches and permitted to dry. After drying, said treated plants 
are dusted with powdery mildew spores and the dusted plants are then 
placed in a constant temperature room (22.degree. C. 10 hours light and 
45% RH) for from 7 days to 9 days to await disease expression. At the end 
of the holding period, all plants are examined and rated according to the 
performance rating system provided below. 
PERFORMANCE RATING 
All plants were rated for disease severity on a scale of 1-7 (clean-kill), 
as described in Example I above. 
Data obtained are reported in Table III below. 
Table III 
______________________________________ 
Control of Powdery Mildew on Wheat 
______________________________________ 
Rate Disease 
Compound ppm Severity 
______________________________________ 
1,2-Dimethyl-3-(3-methylpiperidino)- 
500 1-Clean 
5-phenylprazolium chloride 
1,2-Dimethyl-3-(3-methylpiperidino)- 
500 1-Clean 
5-phenylpyrazolium perchlorate 
1,2-Dimethyl-3-(3-methylpiperidino)- 
500 1-Clean 
5-phenylpyrazolium iodide 
1,2-Dimethyl-3-(4-methylpiperidio)- 
500 2-Trace 
5-phenylpyrazolium iodide 
1,2-Dimethyl-3-(2-methylpiperidio)- 
500 2-Trace 
5-phenylpyrazolium iodide 
3-(Hexahydro-1H-azepin-1-yl)-1,2- 
500 3-Slight 
dimethyl-5-phenylprazolium iodide 
1,2-Dimethyl-3-phenyl-5-piperidino- 
500 3-Slight 
pyrazolium iodide 
______________________________________ 
From these data it is apparent that 1,2-dimethyl-3-(2,3 or 
4-methylpiperidino)-5-phenylpyrazolium salts are preferred fungicidal 
agents effective for the control of powdery mildew on wheat. 
The following examples illustrate the preparation of the compounds employed 
as fungicides herein. 
EXAMPLE 3 
Preparation of 1-methyl-3-phenyl-2-pyrazolin-5-one 
Ethyl benzoylacetate (1,538 g. 8 moles) dissolved in isopropanol (6l) is 
placed in a 12 l flask under an atmosphere of nitrogen. Methylhydrazine 
(410 g, 8.7 moles, 98%) in isopropanol (800 ml) is added with stirring in 
a dropwise manner to the ethyl benzoylacetate solution prewarmed to about 
80.degree. C. During the addition the external heating is removed. Seeding 
of the reaction mixture with the product at the point of one-third 
addition of methylhydrazine causes a copious precipitate of product. This 
procedure eliminates a large exotherm from occurring at a later stage. 
After the addition is complete, the reaction mixture is held at about 
80.degree. C. for 2 hours. Cooling the slurry to 20.degree. C. and 
filtering off the solid, a yield of 1,131 g (81%) of product after drying 
with a melting point equal to 211.degree. C. is obtained. 
EXAMPLE 4 
Preparation of 5-chloro-1-methyl-3-phenylpyrazole 
To a solution of phosphorous oxychloride (2,015 g, 19 moles) is added solid 
1-methyl-3-phenylpyrazolin-5-one (2,073 g, 11.9 moles) with stirring and 
warming. At 100.degree. C. the mixture becomes homogeneous. The reflux 
temperature rises from 119.degree. C. to 143.degree. C. over a period of 
30 hours. After cooling, the mixture is poured into ice and water (8 l) 
with stirring. After 4 hours the slurry is filtered and the filter cake 
added to 4 l of water containing 1.5 l of 10% sodium hydroxide solution 
with stirring. Removal of the solid by filtration followed by a 
recrystallization from hexane yields 1,523 g of product, having a melting 
point ranging fromm 61.degree. C. to 62.degree. C. 
EXAMPLE 5 
Preparation of 3-chloro-1,2-dimethyl-5-phenylpyrazolium methyl sulfate, 
utilizing one of two methods 
METHOD (A) 
Dimethyl sulfate (30 g, 0.22 mole) is added to a stirred solution of 
5-chloro-1-methyl-5-phenylpyrazole (39.5 g, 0.2 mole) in dry xylene (350 
ml) and the reaction mixture is warmed to 105.degree. C. to 115.degree. C. 
for 18 hours. A brown syrup separates out, the reaction is cooled and the 
xylene is decanted off. Dry acetone (300 ml) is added and after stirring a 
white precipitate separates out and is filtered off, mp 100.degree. C. to 
102.degree. C. 33.8 g, (55%). Recrystallization from dry acetone-toluene 
(1.1) gives white needles mp 102.degree. C. to 104.degree. C. 
Analysis calculated for C.sub.12 H.sub.15 N.sub.2 CISO.sub.4 : C, 45.22; H, 
4.74; N, 8.79; Cl, 11.13. Found: C, 45.31; H, 4.81; N, 8.93; Cl, 11.24. 
METHOD (B) 
To a solution of dimethyl sulfate (1,596 g, 12.66 moles) at 70.degree. C. 
to 74.degree. C. is added 5-chloro-1-methyl-3-phenylpyrazole (1,523 g, 
7.912 moles). During the exothermic addition the heat source is removed. 
After the exothermic reaction has ceased the reaction mixture is 
maintained at 80.degree. C. by external heating for 2 hours and then is 
poured into toluene. Toluene is decanted off, leaving a residual syrup, 
which is treated with additional toluene and decanted off as above. The 
syrup is dissolved in chloroform, filtered, and the filtrate evaporated to 
an oil, which crystallizes from acetone to yield 1.52 kg, (60.3%) mp 
95.degree. C. to 96.degree. C. 
EXAMPLE 6 
Preparation of 3-chloro 1,2-dimethyl-5-phenylpyrazolium iodide 
To an aqueous solution of 1,2-dimethyl-3-chloro-5-phenylpyrazolium methyl 
sulfate is added a saturated aqueous solution of sodium iodide at 
5.degree. C. A copious precipitate is formed and filtered off. The solid 
is dissolved in methylene chloride and precipitated with diethyl ether to 
yield almost white crystals mp 162.degree. C. to 164.degree. C. 
Analysis calculated for C.sub.11 H.sub.12 N.sub.2 Cll: C, 39.49; H, 3.62; 
N, 8.38; Cl, 10.64; I, 37.93. Found: C, 39.46; H, 3.61; N, 8.44; Cl, 
10.47; I, 37.85. 
EXAMPLE 7 
Preparation of 3-cyclohexyl-1-methyl-2-pyrazolin-5-one 
To ethyl 3-oxo-cyclohexanepropionic acid (4.4 g, 0.234 mole) in n-propanol 
(500 ml) is added dropwise with stirring under nitrogen at 80.degree. C. 
methylhydrazine (13.8 g, 0.3 mole). After heating at reflux during 5 
hours, the reaction is cooled and evaporated to a residual oil. 
Crystallization from ethylacetate gives a white powder mp 170.5.degree. C. 
to 172.degree. C. 
Analysis calculated for C.sub.10 H.sub.10 N.sub.20 ; C, 66.63 H, 8.95; N, 
15.54. Found: C, 66.59; H, 9.07; N, 15.69. 
EXAMPLE 8 
Preparation of 5-chloro-3-cyclohexyl-1-methylpyrazole 
Phosphorus oxychloride (15.3 g, 0.1 mole) is added to 
3-cyclohexyl-1-methyl-2-pyrazolin-5-one and the mixture stirred and heated 
at 120.degree. C. to 135.degree. C. for 8 hours. The cooled reaction 
mixture is then poured into ice-water, made alkaline with 1% aqueous 
sodium hydroxide and extracted with methylene chloride. Removal of solvent 
under reduced pressure, then in vacuo at 70.degree. C. affords an oil, 8 
g, (93.8%). 
Analysis calculated for C.sub.10 H.sub.15 N.sub.2 Cl; C, 60.45; H, 7.61; N, 
14.10; Cl, 17.85. Found: C, 60.28; H, 7.55; N, 14.20; Cl, 17.79. 
EXAMPLE 9 
Preparation of 3-chloro-5-cyclohexyl-1,2-dimethylpyrazolium methyl sulfate 
[and hydrogen sulfate (1:1)] 
A mixture of 5-chloro-3-cyclohexyl-1-methylpyrazole (7 g, .0352 mole) and 
dimethyl sulfate (8.82 g, 0.07 mole) is heated to 80.degree. C. and the 
heating source then removed. The reaction temperature rises to 88.degree. 
C. and then, after the exotherm, the temperature is maintained at 
80.degree. C. by external heating for 6 hours. Toluene (100 ml) is added 
to the cooled reaction and the mixture is set aside overnight at room 
temperture and then a waxy solid is filtered off. Crystallization from 
methylene chloride-ether affords a granular product, mp 70.degree. C. to 
73.5.degree. C., 11.2 g (100%). NMR and infrared spectra indicate a 
mixture of CH.sub.3 SO.sub.4 and HSO.sub.4 anions. 
Analysis calculated for C.sub.12 H.sub.21 N.sub.2 ClSO.sub.4 (as CH.sub.3 
SO.sub.4): C,44.36; H, 6.57; N, 8.63; S, 9.87; Cl, 10.92. Found C, 41.34; 
H, 6.24; N, 8.14; S, 9.12; Cl, 10.31. 
A portion of the above compound is readily converted to the perchlorate 
whose melting point ranges from 216.degree. C. to 218.degree. C. 
EXAMPLE 10 
Preparation of 3,4,5-Tribromo-1-methylpyrazole 
To 3,4,5-tribromopyrazole (4.5 g, 0.15 mole) in 3N aqueous sodium hydroxide 
(6 g, 0.15 mole) is added at room temperature with stirring dimethyl 
sulfate (19 g, 0.15 mole). After 10 minutes a solid separates out. An 
additional gram of dimethyl sulfate is added and the mixture is stirred 
for 3 days, filtered and the precipitate water washed and air dried to 
yield 33 g (73%), mp 85.degree. C. to 86.degree. C. Crystallization from 
cyclohexane yields desired solid product whose melting point ranges from 
about 90.degree. C. to 91.degree. C. 
Analysis calculated for C.sub.4 H.sub.3 N.sub.2 Br.sub.3 : C, 15.07; H, 
0.95; N, 8.79; Br, 75.21. Found: C, 15.16; H, 0.82; N, 8.7; Br 75.36. 
EXAMPLE 11 
Preparation of 3,4,5-tribromo-1,2-dimethylpyrazolium methyl sulfate (and 
perchlorate) 
A stirred suspension of 1-methyl-3,4,5-tribromopyrazole (19.3 g, 0.06 mole) 
in dimethyl sulfate (80 ml) is stirred and heated at 130.degree. C. to 
135.degree. C. for 6 hours. On cooling and setting aside overnight, a 
solid is obtained and filtered off, benzene washed and air dried to yield 
18.7 g, (70%) whose melting point ranges from 199.degree. C. to 
203.degree. C. 
Analysis calculated for C.sub.6 H.sub.9 N.sub.2 Br.sub.3 SO.sub.4 : C, 
16.19; H, 2.04; N, 6.29; Br, 53.88; S, 7.20. Found: C, 16.19; H, 1.99; N, 
6.38; Br, 53.98; S, 7.31. 
Treatment of the above methyl sulfate compound with aqueous perchloric acid 
affords the perchlorate whose melting point ranges from 300.degree. C. to 
300.5.degree. C. 
EXAMPLE 12 
Preparation of 1,2-dimethyl-3-phenyl-5-piperidinopyrazolium iodide and 
perchlorate 
Piperidine (2.56 g, 0.03 mole) is added to 1,2-dimethy 
3-chloro-5-phenylpyrazolium methyl sulfate (4.77 g, 0.015 mole) in 
absolute ethanol (30 ml) and the mixture stirred with a bar magnet and 
heated under reflux for 4 hours. After cooling, the reaction mixture is 
evaporated under reduced pressure to a brown oil, and then dissolved in 50 
ml of aqueous saturated sodium bicarbonate solution. The aqueous layer is 
extracted with ether and this organic layer discarded, then with 
chloroform (3.times.100 ml). Evaporation of the chloroform layer affords 
1,2-dimethyl-3-phenyl-5-piperidinopyrazolium methyl sulfate as a viscous 
oil. The oil is redissolved in water and saturated aqueous potassium 
iodide solution is added. (Sodium iodide is also equally effective). An 
immediate copious white precipitate of 
1,2-dimethyl-3-phenyl-5-piperidinopyrazolium iodide is formed, then 
filtered and washed with ice cold water to give 3.37 g, (56%) of product 
mp 179.degree. C. to 180.degree. C. The melting point is unchanged by 
dissolving in chloroform, filtering and reprecipitating with diethyl ether 
and filtering off the solid. For analysis see Table I, compound 1. 
Treatment of a portion of the iodide dissolved in warm water with 10% 
aqueous perchloric acid gives a white solid which after cooling to 
10.degree. C. is filtered off, mp 137.degree. C. to 138.degree. C.; see 
compound 2, Table I. This material is also obtained directly by treating 
an aqueous solution of the methyl sulfate (above) with 10% sodium 
perchlorate and filtering off the product. 
EXAMPLE 13 
Preparation of 1,2-Dimethyl-3,5-dipiperidinopyrazolium bromide 
4-Bromo-1,2-dimethyl-3,5-dipiperidinopyrazolium bromide (6.3 g, 0.015 mole) 
is dissolved in methanol (150 ml) and sodium hydroxide (1.2 g, 0.3 mole) 
and treated with 10% palladium on carbon. The mixture is hydrogenated at 
25.degree. C. and absorbs hydrogen (290 ml) uncorrected (86%) in 25 
minutes. The catalyst is filtered off, washed with ethanol and aqueous 
hydrogen bromide (10 ml) is added. The mixture is evaporated in vacuo to 
an oil, which is dissolved in chloroform and precipitated with diethyl 
ether to give a white powder on filtration mp 211.degree. C. to 
212.degree. C., 3.4 g, (69%). Analysis see compound 10, Table IV. 
A small amount of the bromide is dissolved in water and converted with 10% 
perchloric acid in quantitative yield to the perchlorate mp 171.degree. C. 
to 172.degree. C., compound 11, Table IV. 
EXAMPLE 14 
Following the procedure of Method A or Method B above, there are obtained 
the compounds identified in Table IV in good yields and purity. 
Table IV 
__________________________________________________________________________ 
##STR9## 
No. 
##STR10## 
X R.sub.4 
R.sub.3 
Method (%) Yield 
(.degree. C) 
Analysis Calculated 
% 
__________________________________________________________________________ 
Found 
1 
##STR11## 
1.sup.- 
H 
##STR12## 
A A salt(Nal on intermediate (CH.sub.3 SO.sub.4) 
56 179-180 
C H N 
30.14 5.80 10.96 
C H N 
49.74 5.61 
10.91 
2 
##STR13## 
ClO.sub.4.sup.- 
H 
##STR14## 
A A acid(HClO.sub.4 on intermediate (CH.sub.3 
SO.sub.4) 95 137-138 
C H N 
54.01 6.23 11.80 
C H N 
53.80 6.07 
11.71 
3 
##STR15## 
CH.sub.3 SO.sub.4.sup.- 
H 
##STR16## 
A 63 112-114 
C H N 
55.57 6.86 11.44 
C H N 
55.14 6.70 
12.17 
4 
##STR17## 
1.sup.- 
H 
##STR18## 
A 75 122-124.5 
C H N 
51.40 6.09 10.58 
C H N 
51.39 6.23 
10.38 
5 
##STR19## 
1.sup.- 
H 
##STR20## 
A 45 184.5-185 
C H N 
51.40 6.09 
C H N 
51.30 6.07 
10.55 
6 
##STR21## 
1.sup.- 
H 
##STR22## 
A 51 151-152 
C H N 
51.40 6.09 10.56 
C H N 
51.07 6.13 
10.74 
7 
##STR23## 
1.sup.- 
H 
##STR24## 
A 51 143-144.5 
C H N 
51.40 6.09 10.58 
C H N 
50.38 6.08 
10.54 
8 
##STR25## 
Br.sup.- 
Br 
##STR26## 
B 88 170-170.5 
C H N Br 
42.67 6.21 13.27 
37.85 
C H N Br 
42.77 45.98 
13.28 37.93 
9 
##STR27## 
ClO.sub.4.sup.- 
Br 
##STR28## 
B Acid(HClO.sub.4 on Br.sup.-) 
-- 154-155 
C H N Br 
40.77 6.93 12.68 
18.09 
C H N Br 
40.79 6.01 
12.77 18.14 
10 
##STR29## 
Br.sup.- 
H 
##STR30## 
B Hydrogenration Pd/C/H.sub.1 /NaOH 
69 211-212 
C H N Br 
52.48 7.93 16.32 
23.28 
C H N Br 
52.33 7.66 
16.04 22.64 
11 
##STR31## 
ClO.sub.4.sup.- 
H 
##STR32## 
B HClO.sub.4 on compound 10 
95 170-171 
C H N 
49.64 7.50 15.44 
C H N 
49.38 7.68 
15.08 
12 
##STR33## 
ClO.sub.4.sup.- 
H 
##STR34## 
A Acid(HClO.sub.4 on compund 14 the CH.sub.2 
SO.sub.4.sup.-) 
54 110-112 
C H N 
55.21 6.54 11.36 
C H N 
54.01 6.51 
10.92 
13 
##STR35## 
Br.sup.- 
H 
##STR36## 
A Acid(HBr on compound 14 the CH.sub.3 SO.sub.4.s 
up.-) 60 144-146 
C H N 
58.28 6.91 11.99 
C H N 
57.92 6.77 
11.89 
14 
##STR37## 
CH.sub.2 SO.sub.4.sup.- 
H 
##STR38## 
A 67 glass C H N 
56.68 7.14 11.02 
C H N 
50.39 7.15 
11.20 
15 
##STR39## 
Cl.sup.- 2H.sub.2 O 
H 
##STR40## 
Ion exchange on Dowex 1-X8-Cl anion, using 
compound 14 CH.sub.3 SO.sub.4.sup.- 
13 47 70.5-72 
C H N Cl 
59.90 8.6 11.67 
11.61 
C H N Cl 
60.64 8.1 
12.58 10.21 
16 
##STR41## 
CH.sub.2 SO.sub.4.sup.- 
H 
##STR42## 
A 67 glass C H N 
56.66 7.14 11.02 
C H N 
55.07 7.09 
10.60 
17 
##STR43## 
Cl.sup.- 
H 
##STR44## 
Ion exchange on Dowex 1-X8-Cl anion using 
compound 16 
60 oil N Cl 
12.27 20.72 
N Cl 
11.70 19.92 
18 
##STR45## 
ClO.sub.4.sup.- 
H 
##STR46## 
A Salt NaClO.sub.4 on compound 
-- 94-95 C H N 
55.21 6.54 11.36 
C H N 
54.94 6.48 
11.38 
19 
##STR47## 
CH.sub.3 SO.sub.4.sup.- Cl.sup.- (75:25) 
H 
##STR48## 
A 98 glass C* H* N* 5* Cl 
55.78 8.58 10.84 
8.27 C H N S Cl 
51.91 8.16 
10.38 6.83 
2.56 
20 
##STR49## 
1.sup.- 
H 
##STR50## 
A Salt Nal on compound 19 
-- glass C H N I 
50.62 7.50 10.42 
31.47 
C H N I 
50.59 7.89 
10.42 30.60 
21 
##STR51## 
1.sup.- 
H 
##STR52## 
A Salt Nal on CH.sub.3 SO.sub.4.sup.- salt 
-- 99-100 C H N H 
49.39 7.25 10.80 
32.60 
C H N I 
47.99 7.24 
10.42 31.61 
22 
##STR53## 
I.sup.- 
Br 
##STR54## 
A 75 193-194 
C H N Br I 
42.87 4.87 8.82 
16.78 26.65 
C H N Br I 
42.81 4.33 
8.82 16.90 
26.68 
23 
##STR55## 
I.sup.- 
Br 
##STR56## 
A 63 211-213 
C H N Br I 
42.87 4.87 8.82 
16.78 26.65 
C H N Br I 
42.58 5.00 
8.78 16.89 
26.56 
24 
##STR57## 
ClO.sub.4.sup.- 
Br 
##STR58## 
A 6 197-199 
N 9.20 
N 8.91 
25 
##STR59## 
I.sup.- 
Br 
##STR60## 
A 16 201-202 
C H N Br 
41.58 4.58 9.09 
17.29 
C H N Br 
39.15 4.38 
8.66 16.30 
__________________________________________________________________________ 
*[as CH.sub.2 SO.sub.4 ]-