N-acetonylbenzamides and their use as fungicides

Novel N-acetonylbenzamides and their use in controlling phytopathogenic fungi.

BACKGROUND 
The present invention relates to certain N-acetonyl-substituted benzamides 
and their use in controlling fungi, particularly phytopathogenic fungi. 
It is known that benzamides of the class of 
N-(1,1-dialkyl-3-chloroacetonyl)substituted benzamides exhibit fungicidal 
activity, see, e.g. U.S. Pat. Nos. 3,661,991 and 3,751,239. The practical 
value of such compounds in the treatment of fungal infections of plants is 
limited by the substantial phytotoxicity also exhibited by the compounds. 
It has been recognized that the phytotoxicity of such N-acetonyl 
substituted benzamides can be reduced by altering the substituents on the 
terminal carbon to other than only hydrogen or chlorine, see, e.g. U.S. 
Pat. Nos. 4,822,902 and 4,863,940. 
DESCRIPTION OF THE INVENTION 
Phytopathogenic fungi are controlled by application of a fungicidally 
effective amount of compounds of the formula (1): 
##STR1## 
wherein: R.sub.1 and R.sub.3 are each independently halo or (C.sub.1 
-C.sub.4)alkyl; 
R.sub.2 is (C.sub.1 -C.sub.4)alkyl, (C.sub.2 -C.sub.4)alkenyl, (C.sub.2 
-C.sub.6)alkynyl, (C.sub.1 -C.sub.4)alkoxy or cyano; 
R.sub.4 and R.sub.5 are independently H or (C.sub.1 -C.sub.4)alkyl, 
provided that at least one of R.sub.4, R.sub.5 is (C.sub.2 -C.sub.4)alkyl; 
and 
X is halo, thiocyano or isothiocyano; or an agronomically acceptable salt 
thereof. 
(C.sub.1 -C.sub.4)alkyl is a straight or branched alkyl group having one to 
four carbon atoms per group and includes methyl, ethyl, n-propyl, 
iso-propyl, n-butyl, isobutyl, sec-butyl and tert-butyl. 
(C.sub.2 -C.sub.4)alkenyl is a straight or branched alkenyl group having 
two to four carbon atoms per group and includes, e.g., ethenyl, 
2-propenyl, 2-butenyl, 1-methylethenyl, 2-methyl-2-propenyl. 
(C.sub.2 -C.sub.6)alkynyl is a straight or branched alkynyl group having 
from two to six carbons per group and includes, e.g., ethynyl, 2-propynyl, 
2-butynyl. 
Halo includes chloro, fluoro, bromo and iodo. 
(C.sub.1 -C.sub.4)alkoxy is a straight or branched alkoxy group having one 
to four carbon atoms per group and includes, e.g., methoxy, ethoxy, 
propoxy, isopropoxy, butoxy, isobutoxy, sec-butoxy and tert-butoxy. 
Agronomically acceptable salts include, e.g., metal salts such as sodium, 
potassium, calcium and magnesium salts, ammonium salts such as isopropyl 
ammonium salts and trialkylsulfonium salts such as triethylsulfonium 
salts. 
In a preferred embodiment, R.sub.1 and R.sub.3 are each independently 
chloro, fluoro, or bromo, R.sub.2 is (C.sub.1 -C.sub.4)alkyl, (C.sub.1 
-C.sub.4)alkoxy or cyano and X is chloro. 
In a highly preferred embodiment, R.sub.1 and R.sub.2 are each chloro, 
R.sub.2 is (C.sub.1 -C.sub.4)alkyl, (C.sub.1 -C.sub.4)alkoxy or cyano, 
R.sub.4 is ethyl, R.sub.5 is methyl and X is chloro. 
The compounds of the present invention are useful in controlling 
phytopathogenic fungi, particularly fungi of the class Oomycetes, and 
exhibit high fungicidal activity and relatively low phytotoxicity. 
Important genera of the Oomycetes include Phytophthora, Plasmopara, 
Peronospora and Pseudoperonospora which cause diseases such as potato and 
tomato late blight, and downy mildew in grapes and other crops. 
The compounds of the present invention can be applied as fungicidal sprays 
by methods commonly employed, such as conventional high-gallonage 
hydraulic sprays, low-gallonage sprays, air-blast, aerial sprays and 
dusts. The dilution and rate of application will depend upon the type of 
equipment employed, the method and frequency of application desired and 
diseases to be controlled, the effective amount is typically from about 
0.01 kilogram (kg) compound per hectare to about 20 kg compound per 
hectare, preferably from about 0.1 kg compound per hectare to about 5 kg 
compound per hectare and more preferably from about 0.125 kg compound per 
hectare to about 0.5 kg compound per hectare. 
The compounds of the present invention are useful for the control of 
phytopathogenic fungi on crops and may be used as seed protectants, soil 
fungicides and/or foliar fungicides. As a seed protectant, a compound of 
the present invention is coated on seed at a dosage rate of about 10 grams 
(g) compound per 50 kg seed to about 20 g compound per 50 kg seed. As a 
soil fungicide, a compound of the present invention can be incorporated in 
the soil or applied to the surface of the soil at a dosage rate of about 
0.5 kg compound per hectare to about 20 kg compound per hectare and 
preferably at a rate of about 1 kg compound per hectare to about 5 kg 
compound per hectare. As a foliar fungicide, a compound of the present 
invention is applied to growing plants at a dosage rate of about 0.1 kg 
compound per hectare to about 5 kg compound per hectare and preferably at 
a rate of about 0.125 kg compound per hectare to about 0.5 kg compound per 
hectare. 
For the above disclosed purposes these compounds can be used in the 
technical or pure form as prepared, as solutions or as formulations. The 
compounds are usually taken up in a carrier or are formulated so as to 
render them suitable for subsequent use as fungicides. For example, the 
compounds can be formulated as wettable powders, dry powders, emulsifiable 
concentrates, dusts, granular formulations, aerosols, or flowable emulsion 
concentrates. In such formulations, the compounds are extended with a 
liquid or solid carrier and, when dried, suitable surfactants are 
incorporated. 
It is usually desirable, particularly in the case of foliar spray 
formulations, to include adjuvants, such as wetting agents, spreading 
agents, dispersing agents, stickers, adhesives and the like in accordance 
with agricultural practices. Such adjuvants commonly used in the art can 
be found in McCutcheon's Emulsifiers and Detergents, McCutcheon's 
Emulsifiers and Detergents/Functional Materials and McCutcheon's 
Functional Materials all published annually by McCutcheon Division of MC 
Publishing Company (New Jersey). 
In general, the compounds utilized in this invention can be dissolved in 
appropriate solvents such as acetone, methanol, ethanol, dimethylformamide 
or dimethyl sulfoxide and such solutions extended with water. The 
concentrations of the solution can vary from 1% to 90% with a preferred 
range being 5% to 50%. 
For the preparation of emulsifiable concentrates, the compounds used in the 
invention can be dissolved in suitable organic solvents or a mixture of 
solvents, together with an emulsifying agent which permits dispersion of 
the fungicide in water. The concentration of the active ingredient in 
emulsifiable concentrates is usually 10% to 90% and in flowable emulsion 
concentrates, this can be as high as 75%. Wettable powders suitable for 
spraying, can be prepared by admixing the compound with a finely divided 
solid, such as clays, inorganic silicates and carbonates, and silicas and 
incorporating wetting agents, sticking agents, and/or dispersing agents in 
such mixtures. The concentration of active ingredients in such 
formulations is usually in the range of 20% to 98%, preferably 40% to 75%. 
Dusts are prepared by mixing the compounds of the present invention salts 
and complexes thereof with finely divided inert solids which can be 
organic or inorganic in nature. Inert materials useful for this purpose 
include botanical flours, silicas, silicates, carbonates and clays. One 
convenient method of preparing a dust is to dilute a wettable powder with 
a finely divided carrier. Dust concentrations containing 20% to 80% of the 
active ingredient are commonly made and are subsequently diluted to 1% to 
10% use concentration. 
The compounds of the present invention can also be utilized in combination 
with other fungicides such as: 
(a) dithiocarbamates and derivatives such as: ferric 
dimethyldithiocarbamate (ferbam), zinc dimethyldithiocarbamate (ziram), 
manganese ethylenebisdithiocarbamate (maneb) and its coordination product 
with zinc ion (mancozeb), zinc ethylenebisdithiocarbamate (zineb), zinc 
propylenebisdithiocarbamate (propineb), sodium methyldithiocarbamate 
(metham), tetramethylthiuram disulfide (thiram), the complex of zineb and 
polyethylene thiuram disulfide, 
3,5-dimethyl-1,3,5-2H-tetrahydrothiadiazine-2-thione (dazomet); and 
mixtures of these and mixtures with copper salts; 
(b) nitrophenol derivatives such as: dinitro-(1-methylheptyl) phenyl 
crotonate (dinocap), 2-sec-butyl-4,6-dinitrophenyl-3,3-dimethylacrylate 
(binapacryl), and 2-sec-butyl-4,6-dinitrophenyl isopropyl carbonate; 
(c) heterocyclic structures such as: 
N-trichloromethylthiotetrahydrophthalimide (captan), 
N-trichloromethylthiophthalimide (folpet), 2-heptadecyl-2-imidazole 
acetate (glyodine), 
2-octylisothiazolone-3,2,4-dichloro-6-(o-chloroanilino)s-triazine, diethyl 
phthalimidophosphorothioate, 4-butyl-1,2,4-triazole, 
5-amino-1-[bis(dimethylamino)phosphinyl]-3-phenyl-1,2,4-triazole, 
5-ethoxy-3-trichloromethyl-1,2,4-thiadiazole, 
2,3-dicyano-1,4-dithiaanthraquinone (dithianon), 
1,3-dithiolo-[4,5-b]quinoxaline-2-thione (thioquinox), ethyl 
1-(butylcarbamoyl)-2-benzimidazole carbamate (benomyl), 2-4'-(thiazolyl) 
benzimidazole (thiabendazole), 
4-(2-chlorophenylhydrazono)-3-methyl-5-isoxazolone, 
3-(3,5-dichlorophenyl)-5-ethenyl-5-methyl-2,4-oxazolidinedione 
(vinolozolin); 
3-(3,5-dichlorophenyl)-N-(1-methylethyl)-2,4-dioxo-1-imidazolidinecarboxam 
ide (iprodione); 
N-(3,5-dichlorophenyl)-1,2-dimethylcyclopropane-1,2-dicarboximide 
(procymidone); 
beta-(4-dichlorophenoxy)-alpha-(1,1-dimethylethyl)-1H-1,2,4-triazole-1-eth 
anol (triadimenol); 
1-(4-chlorophenoxy)-3,3-dimethyl-1-(1H-1,2,4-triazol-1-yl)-2-butanone 
(triadimefon); 
beta-[1,1'-biphenyl)-4-yloxyl]-alpha-(1,1-dimethylethyl)-1H-1,2,4-triazole 
-1-ethanol (bitertanol); 2,3-dichloro-N-(4-fluorophenyl)maleimide 
(fluoroimide); 
1-[2-(2,4-dichlorophenyl)-4-propyl-1,3-dioxolan-2-ylmethyl]-1H-1,2,4-triaz 
ole; pyridine-2-thiol-1-oxide, 8-hydroxyquinoline sulfate and metal salts 
thereof; 2,3-dihydro-5-carboxanilido-6-methyl-1,4-oxathiin-4,4-dioxide, 
2,3-dihydro-5-carboxanilido-6-methyl-1,4-oxathiin, 
alpha(phenyl)-alpha-(2,4-dichlorophenyl)-5-pyrimidinylmethanol 
(triarimol), cis-N-[1,1,2,2-tetrachloroethyl)thio]-4-cyclohexene-1,2-dicar 
boximide, 3-[2-(3,5-dimethyl-2-oxycyclohexyl)-2-hydroxy]glutarimide 
(cycloheximide), dehydroacetic acid, 
N-(1,1,2,2-tetrachloroethylthio)-3a,4,7,7a-tetrahydrophthalimide 
(captafol), butyl-2-ethylamino-4-hydroxy-6-methylpyrimidine (ethirimol), 
acetate of 4-cyclodecyl-2,6-dimethyl-morpholine (dodemorph), 
4-[3-(4-chlorophenyl)-3-(3,4-dimethoxyphenyl)acryloyl]morpholine 
(dimethomorph) and 6-methyl-2-oxo-1,3-dithiolo[4,5-b]-quinoxaline 
(quinomethionate). 
(d) miscellaneous halogenated fungicides such as: 
tetrachloro-p-benzoquinone (chloranil), 2-3-dichoro-1,4-napththoquinone 
(dichlone), 1,4-dichloro-2,5-dimethoxybenzene (chloroneb), 
3,5,6-trichloro-o-anisic acid (tricamba), 
2,4,5,6-tetrachloroisophthalonitril (TCPN), 2,6-dichloro-4-nitroaniline 
(dichloran), 2-chloro-1-nitropropane, polychloronitrobenzenes such as 
pentachloronitrobenzene (PCNB) and tetrafluorodichloroacetone; 
(e) fungicidal antibiotics such as: griseofulvin, kasugamycin and 
streptomycin; 
(f) copper-based fungicides such as: copper hydroxide, cuprous oxide, basic 
cupric chloride, basic copper carbonate, copper terphthalate, copper 
naphthenate and Bordeaux mixture; and 
(g) miscellaneous fungicides such as: diphenyl, sulfone, dodecylguanidine 
acetate (dodine), aluminum tris-o-ethyl phosphonate(fosetyl-al), 
N-(2,6-dimethylphenyl)-N-(methoxyacetyl)alanine methyl ester(methoxyl) and 
other alkaline fungicides, phenylmercuric acetate, 
N-ethylmercuri-1,2,3,6-tetrahydro-3,6-endomethano-3,4,5,6,7,7-hexachloroph 
thalimide, phenylmercuric monoethanol ammonium lactate, 
p-dimethylaminobenzene sodium sulfonate, methyl isothiocyanate, 
1-thiocyano-2,4-dinitrobenzene, 1-phenylthiosemicarbazide, 
nickel-containing compounds, calcium cyanamide, lime sulfur, 
1,2-bis(3,-methoxycarbony-2-thioureido) benzene (thiophanate-methyl), and 
2-cyano-N-(ethylamino)carbonyl)-2-(methoxyimine)acetamide (cymoxanil). 
The benzamide compounds of the present invention can be prepared using 
conventional synthesis techniques, as shown in scheme A. For example, 
compounds of formula (I) can be prepared by treating acetylenic amides 
(II) with a halogen or a halogen source at a temperature of -20.degree. C. 
in the presence of a solvent such as methylene chloride, to give an 
intermediate oxazoline (III) which is readily hydrolyzed under acidic 
conditions using hydrochloric acid and methanol or tetrahydrofuran as 
solvent at a temperature of 40.degree. C. to 50.degree. C. The starting 
acetylenic amides can be prepared by reaction of the corresponding 
aromatic acyl chloride (IV) and an acetylenic amine (V) in the presence of 
a base such as sodium hydroxide, triethylamine or pyridine using water, 
methylene chloride or ethyl ether as a solvent at room temperature. 
##STR2## 
The acetylenic amine (V) can be prepared from the corresponding 
commercially available acetylenic alcohol (VI), as shown in Scheme B. 
##STR3## 
Synthesis techniques for making exemplary benzoyl chloride starting 
materials (IV) are outlined below in Schemes C and D. 
##STR4##

EXAMPLE 1: 
N-[3'-(1'-chloro-3'-methyl-2'-oxopentan]-3,5-dichloro-4-methylbenzamide 
Step a) Preparation of 3,5-dichloro-4-methylbenzoic acid: 
To a solution of p-toluic acid (95.0 g,0.698 mole) in methylene chloride (1 
liter), was added aluminum chloride (260.0 g,1.948 mole), portionwise, 
while keeping the reaction temperature below 10.degree. C. When the 
addition was completed, chlorine gas was bubbled in at such a rate as to 
keep the temperature below 10.degree. C. The reaction was followed by GLC. 
After about 4 hours most of the starting material had been converted to 
the expected compound. The resulting mixture was poured into ice and 
concentrated hydrochloric acid, and then extracted with ethyl acetate 
several times. The combined organic layers were washed with water and then 
dried over anhydrous sodium sulfate. Removing the solvent in the rotavap 
yielded the crude product as a white solid. Recrystalization from 
acetone/water yielded 3,5-dichloro-4-methylbenzoic acid with minor 
impurities 115.4 g (81% yield of product). 
Step b) Preparation of 3,5-dichloro-4-methylbenzoyl chloride: 
A mixture of 3,5-dichloro-4-methylbenzoic acid (230 g, 1.12 moles), thionyl 
chloride (204 g, 1.71 moles), and dimethylformamide (30 milliliters(ml), 
in toluene (1 liter) was slowly warmed to 70.degree. C. and stirred at 
that temperature for 2 hours. The toluene was eliminated in the rotavap to 
yield 276 g of 3,5-dichloro-4-methylbenzoyl chloride, used in the next 
step as such. 
Step c) Preparation of 3-methyl-1-pentyn-3-amine 
In a 2000 ml, four-necked, round-bottomed flask fitted with a thermometer 
in a side-armed adapter connected to a scrubbing system, a mechanical 
stirrer, a 500 ml addition funnel and a bubbling tube connected to a 
lecture bottle of hydrogen chloride gas, were placed 350 ml of 
concentrated hydrochloric acid. This solution was cooled to 5.degree. C., 
and hydrogen chloride gas was bubbled in until the size of the bubbles 
were constant. To this the alcohol was added at such a rate as to keep the 
temperature below 0.degree. C., while simultaneously bubbling hydrogen 
chloride gas through the reaction mixture. The addition took between 2 to 
2.5 hours. After the addition of the alcohol was complete the resulting 
mixture was stirred at -5.degree. C. for an additional 30 to 45 minutes. 
The resulting layers were separated and the organic layer was washed with 
ice-water until the pH of washing liquids was 7. The resulting light 
yellow mobile oil was used in the following step without further 
purification. 
Step d) Preparation of 3-amino-3-methyl-1-pentyne. 
In a 3000 ml, four-necked, round-bottomed flask fitted with a thermometer 
in a side-armed adapter connected to a scrubbing system, a mechanical 
stirrer, a 500 ml addition funnel and a bubbling tube connected to a 
lecture bottle of NH.sub.3 gas, was placed 1000 ml of concentrated 
ammonium hydroxide. This solution was cooled to -5.degree. C., and 
NH.sub.3 gas was bubbled in until the size of the bubbles was constant. To 
this the chloride (600 g) and the 50% NaOH were charged in the addition 
funnels and added to the ammonia solution at such a rate that equal 
stoichiometric amounts of each compound were introduced into the reaction 
flask and that the temperature was kept below 0.degree. C. The addition 
took 2 to 3 hours. After the addition was complete, the reaction mixture 
was stirred 1 hour at -5.degree. C. The phases were separated and the 
organic phase was washed once with ice-water. The light yellow oil 
obtained was codistilled with water at atmospheric pressure. Four 
fractions were separated: 
Fraction 1 (bp 71.degree. to 79.degree. C.) included amine plus low boiling 
olefins. 
Fraction 2 and 3 (bp 80.degree. to 85.degree. C. and 85.degree. to 
89.degree. C.) were pure amine by 1H-NMR (total 220 g). 
Fraction 4 (bp 90.degree. to 99.degree. C.) was a mixture of the amine and 
the starting alcohol. 
Fractions 1 and 4 were combined and dissolved in dry ether, with hydrogen 
chloride gas bubbled in while cooling. In this way 90 g of the pure amine 
hydrochloride was obtained. Total yield from the alcohol was 57%. 
Step e) Preparation of 
N-[3'-(3'-methyl-1'-pentynyl)]-3,5-dichloro-4-methylbenzamide: 
In a 2 liter, three-necked, round-bottomed flask fitted with a mechanical 
stirrer, nitrogen inlet and thermometer were placed 142 g of 
3-methyl-1-pentyn-3-amine hydrochloride, 300 ml of tetrahydrofuran and 350 
ml of dimethylformamide. To the resulting well stirred mixture was added 
slowly 212 ml of triethylamine, keeping the temperature between 5.degree. 
to 10.degree. C. To the resulting mixture was added 221 g of the preceding 
acyl chloride at such a rate to keep the reaction temperature at 5.degree. 
to 10.degree. C. After the addition was complete, the reaction mixture was 
stirred at room temperature for 3 hours, poured into 2 liters of water and 
extracted with ethyl acetate (3.times.400 ml). The combined organic layers 
were washed with water (1.times.300 ml), then with 5% aqueous hydrochloric 
acid (2.times.300 ml), then with water (1.times.300 ml), then with 5% 
aqueous sodium carbonate (2.times.300 ml) and then again with water ( 
2.times.300 ml), then dried over anhydrous sodium sulfate. The solvent was 
removed in the rotavap yielding 266 g of 
N-[3'-(3'-methyl-1'-pentynyl)]-3,5-dichloro-4-methylbenzamide. 
Step f) Preparation of 
2-(3,5-dichloro-4-methylphenyl)-4-methyl-4-ethyl-5-chloromethylenyloxazoli 
ne 
In a 3 liter, three-necked, round-bottomed flask fitted with a mechanical 
stirrer, a thermometer and a 100 ml addition funnel was dissolved 143 g, 
0.503 mole of 
N-[3'-(3'-methyl-1'-pentynyl)]-3,5-dichloro-4-methylbenzamide in 750 ml of 
methylene chloride. The resulting mixture was cooled down to -50.degree. 
C. and a cold chlorine solution in methylene chloride (800 ml, 0.528M) was 
added very slowly. When the addition was completed, the reaction mixture 
was stirred at -65.degree. C. for 30 minutes. The crude reaction mixture 
was evaporated in the rotavap yielding 168.5 g of 
2-(3,5-dichloro-4-methylphenyl)-4-methyl-4-ethyl-5-chloromethylenyloxazoli 
ne as a light yellow solid which was used as such in the next step. 
Step g) Preparation of 
N-[3'-(1'-chloro-3'-methyl-2'-oxopentan)]-3,5-dichloro-4-methylbenzamide: 
168 g, 0.473 moles, of 
2-(3,5-dichloro-4-methylphenyl)-4-methyl-4-ethyl-5-chloromethylenyloxazoli 
ne prepared in the preceding step was dissolved in 1.6 liters of 
tetrahydrofuran, 250 ml of water, and 60 ml of concentrated hydrochloric 
acid, warmed to 55.degree. C. and stirred at that temperature for four 
hours. The crude reaction mixture was cooled down and poured into a 
mixture of ice and water and then extracted with methylene chloride 
(4.times.400 ml). The combined organic layers were washed with brine, and 
then dried. The solvent was evaporated in the rotavap yielding the 
N-[3'-(1'-chloro-3'-methyl-2'-oxopentan)]-3,5-dichloro-4-methylbenzamide. 
EXAMPLE 2 
N-[3'-(1'-chloro-3'-methyl-2'-oxopentan]-3,5-dichloro-4-ethylbenzamide 
This compound was prepared by the method set forth above in Example 1 
starting with 4-ethylbenzoic acid. 
EXAMPLE 3 
N-[3'-(1'-chloro-3'-methyl-2'-oxopentan]-3,5-dichloro-4-ethoxybenzamide, 
and 
EXAMPLE 4 
N-[3'-(1'-chloro-3'-methyl-2'-oxopentan]-3,5-dichloro-4-methoxybenzamide 
The compounds of Examples 3 and 4 were prepared by the method set forth 
above in Example 1 starting with 3,5-dichloro-4-hydroxybenzoic acid, from 
which the ethyl and methyl ether derivatives were made. 
EXAMPLE 5 
N-[3'-(1'-chloro-3'-methyl-2'-oxopentan)]-4-cyano-3,5-dichlorobenzamide 
Step a) Preparation of 4-cyano-3,5-dichlorobenzoic acid 
In a 100 ml round-bottomed flask was placed 25 ml of concentrated sulfuric 
acid, cooled down to 5.degree. C. To this well stirred liquid was added 
3.82 g (0.055 mole) of sodium nitrite. The resulting mixture was warmed to 
50.degree. C. until a solution was obtained (approx 30 minutes). The 
resulting solution was cooled down to 0.degree. C. (ice-bath). 10.0 g 
(0.049 mole) of 4-amino-3,5-dichlorobenzoic acid were added to the 
solution portion-wise, over a 45 minute period, with vigorous stirring, 
all the while keeping the temperature between 3.degree. to 5.degree. C. 
After the addition was complete, the resulting mixture was allowed to warm 
up to 15.degree. C. and was then stirred at that temperature for 90 
minutes. The mixture was then poured into a mixture of 17.3 g (0.26 mol) 
potassium cyanide in 50 ml of water at 15.degree. C. with vigorous 
stirring. The resulting mixture was warmed up to 35.degree.-40.degree. C. 
for 40 minutes, then cooled to room temperature and then extracted with 
ethyl acetate. The combined organic layers were washed with water, and 
then dried over anhydrous magnesium sulfate. The solvent was then removed 
in the rotavap, yielding 4.07 g of 
N-[3'-(1'-chloro-3'-methyl-2'-oxopentan)]-4-cyano-3,5-dichlorobenzamide. 
This compound was used as such in the next step. 
Step b) 4-cyano-3,5-dichlorobenzoyl chloride 
To 4-cyano-3,5-dichlorobenzoic acid (4.07 g, 0.019 mol) dissolved in 100 ml 
of dry toluene were added thionyl chloride (1.4 ml, 0.019 mol) and 
dimethylformamide (2 drops). The resulting mixture was refluxed during 3 
hours, cooled down to room temperature and the solvent eliminated in the 
rotavap. The residue was dried under vacuum and used as such in the 
following step. 
Step c) N-[3'-methyl-1'-pentynyl)]-4-cyano-3,5-dichlorobenzamide 
To a well stirred mixture of 4-cyano-3,5-dichlorobenzoyl chloride (4.0 g, 
0.017 mol) and water (100 ml) at 0.degree. C. (ice-water bath) were added 
3-amino-3-methyl-1-pentyne hydrochloride and 50 weight percent aqueous 
sodium hydroxide (10 ml). The resulting mixture was stirred 1 hour at 
0.degree. C., warmed up to room temperature and extracted with ethyl 
acetate (3.times.50 ml), the combined organic layers were washed with 
water (3.times.50 ml), and then dried over anhydrous sodium sulfate. The 
solvent was then eliminated in the rotavap, yielding the crude product as 
a yellow oil (2.79 g). The crude product was purified by Michel-Miller 
chromatographic column packed with Merck (grade 60) silica gel using ethyl 
acetate as solvent, yielding 0.75 g of 
N-[3'-methyl-1'-pentynyl)]-4-cyano-3,5-dichlorobenzamide. 
Step d) Preparation of 
2-(4-cyano-3,5-dichlorophenyl)-4-methyl-4-ethyl-5-chloromethylenyloxazolin 
e 
In a 50 ml, three-necked, round-bottomed flask fitted with a magnetic 
stirrer, a thermometer and a 10 ml addition funnel were dissolved 0.5 g 
(1.7 millimoles) of 
N-[3'-(3'-methyl-1'-pentynyl)]-4-cyano-3,5-dichlorobenzamide in 25 ml 
methylene chloride. The resulting mixture was cooled down to -50.degree. 
C. and a cold chlorine solution in methylene chloride (1.7 ml, 1.0M) was 
added very slowly. When the addition was completed, the reaction mixture 
was stirred at -65.degree. C. for 30 minutes. The solvent was evaporated 
from the crude reaction mixture in the rotavap yielding 
2-(4-cyano-3,5-dichlorophenyl)-4-methyl-4-ethyl-5-chloro-methylenyloxazoli 
ne as a light yellow solid which was used as such in the next step. 
Step e) Preparation of 
N-[3'-(1'-chloro-3'-methyl-2'-oxopentan)]-4-cyano-3,5-dichlorobenzamide 
The crude product from the preceding step was dissolved in a 50 mL of 
methanol, 2 ml of water, and 3 ml of concentrated hydrochloric acid, 
warmed up to 55.degree. C. and stirred at that temperature during four 
hours. The crude reaction mixture was cooled down and poured into a 
mixture of ice and water, then neutralized with saturated aqueous sodium 
bicarbonate and then extracted with methylene chloride (4.times.50 ml). 
The combined organic layers were washed with brine and then dried. The 
solvent was evaporated in the rotavap, yielding the crude product, which 
was purified by column chromatography yielding 120 mg of 
N-[3'-(1'-chloro-3'-methyl-2'-oxopentan)]-4-cyano-3,5-dichlorobenzamide. 
Exemplary compounds of the present invention are set forth in Table 1. 
TABLE 1 
______________________________________ 
N-acetonylbenzamides of the structural formula: 
##STR5## 
Ex. No. R.sub.1 
R.sub.2 R.sub.3 
R.sub.4 R.sub.5 
X 
______________________________________ 
1 Cl CH.sub.3 Cl CH.sub.2 CH.sub.3 
CH.sub.3 
Cl 
2 Cl CH.sub.2 CH.sub.3 
Cl CH.sub.2 CH.sub.3 
CH.sub.3 
Cl 
3 Cl OCH.sub.2 CH.sub.3 
Cl CH.sub.2 CH.sub.3 
CH.sub.3 
Cl 
4 Cl OCH.sub.3 Cl CH.sub.2 CH.sub.3 
CH.sub.3 
Cl 
5 Cl CN Cl CH.sub.2 CH.sub.3 
CH.sub.3 
Cl 
______________________________________ 
Characterization of each of the compounds of Examples 1-5 with respect to 
their NMR spectra is provided below in Table 2. 
TABLE 2 
______________________________________ 
200 MHz, delta scale in ppm, 
Tetramethylsilane (TMS) standard, solvent 
Example Number 
CDl.sub.3 
______________________________________ 
1. 7.70(2, s), 6.80(1, s), 4.40(2, d), 2.50(3, s), 1.65 
(2, s), 1.60(3, s), 0.90(3, t) 
2. 7.70(2, s), 6.75(1, bs), 4.35(2, c), 2.95(2, c), 
2.40-2.10(1, m), 2.10-1.80(1, m), 1.65(3, s), 
1.20(3, t), 0.85(3, t) 
3. 7.70(2, s), 6.90(1, bs), 4.40(2, c), 4.15(2, c), 
2.40-2.10(1, m), 2.10-1.80(1, m), 1.60(3, s), 
1.45(3, t), 0.90(3, t) 
4. 7.75(2, s), 6.90(1, bs), 4.40(2, c), 3.95(3, s), 
2.40-2.10(1, m), 2.10-1.80(1, m), 1.65(3, s), 
0.90(3, t) 
5. 7.85(1, s), 7.15(1, bs), 4.40(2, c), 2.50-2.30 
2.00-1.80(1, m), 1.70(3, s), 0.90(3, t) 
______________________________________ 
EXAMPLE 6 
The compounds of Examples 1-5 were tested for fungicidal activity and 
phytoxicity and compared to results obtained with the compounds of 
Comparative Examples C1-C4 set forth below in Table 3. 
TABLE 3 
______________________________________ 
N-acetonylbenzamides of the structural formula: 
##STR6## 
Ex. No. R.sub.1 R.sub.2 
R.sub.3 
R.sub.4 R.sub.5 
X 
______________________________________ 
C1 Cl OH Cl CH.sub.3 
CH.sub.3 
Cl 
C2 Cl CH.sub.3 
Cl CH.sub.3 
CH.sub.3 
Cl 
C3 Cl H Cl CH.sub.2 CH.sub.3 
CH.sub.3 
Cl 
C4 Cl Cl Cl CH.sub.2 CH.sub.3 
CH.sub.3 
Cl 
______________________________________ 
Fungitoxicity Assay against Pythium Ultimum 
Dilution series of the compounds of Examples 1-5 and Comparative Examples 
C1-C4 were prepared in dimethylsulfoxide, and 0.1 ml of each dilution was 
added to 19.9 ml of a liquid asparagine-sucrose medium (see, Erwin, D. C. 
and Katznelson, K., 1971, Can. J. Microbiol. 7, 15) in 9 cm diameter petri 
dishes to give the desired concentrations of test compound. Each plate was 
inoculated with a mycelial plug, 7 mm diameter, taken from the growing 
edge of a culture of Pythium ultimum grown on potato dextrose agar. Two 
replicate plates were used for each treatment. The increase in mycelial 
dry weight was determined after growth for 48 hours at 25.degree. C. with 
shaking on a gyrotary shaker at 60 revolutions per minute. Pythium EC50 
values were calculated from dose response curves. As used herein, the 
terminology "EC50" means the concentration of test compound required to 
inhibit growth by 50% as compared to a control lacking the test compound. 
Phytotoxicity Assay 
Dilution series of the compounds of Examples 1-5 and C1-C4 were prepared in 
dimethylsulfoxide and 20 microliters (.mu.l) of each dilution was added to 
20 ml of molten nutrient medium, consisting of Murashige and Skoog salt 
base, 2% sucrose and 1% agar, to give the desired concentrations of test 
compound. The mixtures were poured immediately into 9 cm diameter petri 
dishes. Surface-sterilized tobacco seeds were placed on each plate (20 
seeds per plate) and the plates incubated in a vertical position in a 
27.degree. C. incubator with a 16 hour photoperiod. After 7 days the mean 
root lengths were calculated. Tobacco EC50 values were determined from 
dose response curves. 
The ratio of Pythium EC50 value to tobacco EC50 value was calculated for 
each compound to provide an index of the fungicidal activity relative to 
the phytotoxicity for each compound. 
Results of the fungitoxicity and phytotoxicity assays are set forth in 
Table 4 as "Pythium EC50" and "Tobacco EC50", each in units of micrograms 
per milliliter (.mu.g/ml) and "(Pythium EC50/Tobacco EC50)", i.e. the 
ratio of the Pythium EC50 value to the Tobacco EC50 value, obtained for 
each compound. 
TABLE 4 
______________________________________ 
Example Pythium EC50 
Tobacco EC50 
(Pythium EC50/ 
No. (.mu.g/ml) (.mu.g/ml) Tobacco EC50) 
______________________________________ 
1 0.02 0.05 0.4 
2 0.12 0.22 0.55 
3 0.49 1.58 0.31 
4 0.14 0.25 0.56 
5 0.11 0.48 0.23 
C1 10.7 &gt;20 &lt;0.53 
C2 0.09 0.03 3 
C3 0.011 0.004 2.75 
C4 0.08 0.05 1.6 
______________________________________ 
The compounds of Examples 1-5 provide a combination of high fungicidal 
activity and relatively low phytotoxicity while compounds of Comparative 
Examples C1-C4 each provide either a combination of low phototoxicity and 
low fungicidal activity, e.g. Comparative Example C1, or a combination 
high fungicidal activity and relatively high phytotoxicity, e.g. 
Comparative Example C4.