Isothiazolylformamidine derivatives as herbicides

A new class of herbicidal compounds consisting of N'-(substituted-5-isothiazolyl)-N,N-dimethylformamidines in which the 3-substituent on the isothiazole moiety consists of alkyl, alkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, alkylamino and dialkylamino, and the 4-substituent on the isothiazole moiety consists of cyano, carbamoyl, and nitro, and in which the hydrogen of the dimethylformamidine moiety may be substituted by fluorine, chlorine, bromine, or carbonitrile, exhibits preemergence and postemergence herbicidal activity, controlling effectively the growth of a wide spectrum of grassy and broad-leaved plant species. The synthesis of members of this class is described in detail, and the utility of representative compounds is exemplified.

This invention describes novel herbicidal compounds, new herbicidal 
compositions, and new methods for preventing and destroying undesired 
plant growth by post-emergence and preemergence application of said new 
and useful herbicidal compositions to the locus where control is desired. 
Effective control of the growth of a variety of grassy and broad-leaved 
plant species is obtained. At herbicidally effective levels of 
application, some compounds of the invention show selectivity favorable to 
corn and related species. The herbicidal compositions may be applied and 
utilized by commonly accepted methods. 
Herbicidal (5-isothiazolyl)urea compounds having a cyano, carboxamide or 
alkoxycarbonyl group in the 4-position are described in the patent 
literature. See, for example, Belgian Pat. No. 817,903 and published 
French application 2,132,191 for compounds in which the 3-substituent of 
the isothiazole ring is alkyl. Copending applications Ser. No. 697,449, 
Ser. No. 697,457, and Ser. No. 697,458, filed of even date herewith, 
describe (5-isothiazolyl(ureas) where the 3-substituent on the isothiazole 
ring is substituted amino, alkoxy, substituted thio, sulfinyl or sulfonyl, 
and Ser. No. 697,455 describes (5-isothiazolyl)ureas where the 
4-substituent is nitro, also filed of even date herewith. It has now been 
found that excellent herbicidal activity is obtained by having present on 
the 5-position, instead of the urea moiety, a formamidine, 
haloformamidine, or cyanoformamidine moiety. Thus in one aspect of this 
invention, novel herbicidal compounds contain an isothiazole ring having 
the following classes of substituents: on the 3-position, an alkyl, 
alkoxy, substituted amino, alkylthio, alkylsulfinyl or alkylsulfonyl 
group; on the 4-position, a cyano, carboxamide, alkoxycarbonyl or nitro 
group; and on the 5-position, a formamidine or substituted formamidine 
group. 
One group of herbicidal compounds in accordance with this invention has the 
following structure (on which the numbering of the various positions of 
the isothiazole ring is also indicated): 
##STR1## 
wherein R.sub.1 and R.sub.2 are lower alkyl or taken together form a 
divalent radical which may also contain a hetero atom; 
M is cyano, carboxamide, alkoxycarbonyl or nitro; 
Y is alkyl, alkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, alkylamino, 
dialkylamino or a cyclic alkyleneimino group; and 
X is H, F, Cl, Br or CN. 
The alkyl, cycloalkyl and alkenyl groups preferably have less than 10 
carbon atoms. Examples of alkyl groups are methyl, ethyl, propyl, 
isopropyl, isobutyl, sec-butyl, tert-butyl, 2-pentyl, and so forth. The 
alkylene groups preferably contain a total of four or five catenated 
atoms, no more than one of which is oxygen, sulfur or nitrogen. In the 
most preferred compounds, R.sub.1 and R.sub.2 are methyl, M is cyano, Y is 
ethyl, isopropyl or tert-butyl, and X is chlorine, bromine, or hydrogen. 
The compounds of this invention may be prepared, for example, by the 
following reaction sequence: 
##STR2## 
where X is F, Br, or CN. 
In the descriptions which follow, all temperatures are in degrees 
centigrade. All reduced pressures not otherwise designated are pressures 
normally attainable using a water aspirator. 
SYNTHESIS OF INTERMEDIATES 
2-Cyano-3-hydroxy-4-methyl-2-pentenenitrile 
To a mixture of 132.1 g of malononitrile and 345.6 g of potassium carbonate 
in 2 liters of methylene chloride was slowly added during 2 hours 316.4 g 
of isobutyric anhydride. During the addition, the mixture reached the 
reflux temperature where it was maintained an additional 6.5 hours. The 
mixture was then stirred at ambient temperature for an additional 15 
hours, then chilled to -10.degree.. One liter of concentrated hydrochloric 
acid was carefully added to the cold mixture, maintaining the temperature 
below 10.degree. throughout the addition. The acidic mixture was filtered 
and the layers separated. The water layer was extracted with two 300 ml 
portions of methylene chloride; the extracts were combined, washed with 
saturated sodium chloride solution, dried, filtered and concentrated. The 
solid was collected, washed with pentane and dried to give 195.5 g of 
2-cyano-3-hydroxy-4-methyl- 2-pentenenitrile, mp 94.degree.-96.degree.. An 
additional 37 g (mp 87.degree.-90.degree.) was obtained by concentration 
of the filtrate and washings. 
In a similar manner were prepared 2-cyano-3-hydroxy- 2-hexenenitrile, 
liquid purified by distillation on molecular still at 100.degree./9 mm; 
2-cyano-3-hydroxy-4,4-dimethyl- 2-pentenenitrile, mp 
159.degree.-162.degree.; 2-cyano-3-hydroxy-4,4 -dimethyl-2-heptenenitrile, 
mp 92.degree.-93.degree. (ether-toluene reaction solvent); 
2-cyano-3-hydroxy- 5-methyl-2-hexenenitrile, liquid purified by molecular 
distillation at 120.degree./9 mm; and 2-cyano-3-hydroxy- 2-pentenenitrile, 
liquid purified by molecular distillation at 110.degree./10-15 mm. 
3-Chloro-2-cyano-4,4-dimethyl-2-pentenenitrile 
To a solution of 69.6 g of 2-cyano-3-hydroxy-4,4-dimethyl- 2-pentenenitrile 
in 600 ml of methylene chloride was added in small portions 104.1 g of 
phosphorus pentachloride. The mixture was stirred for 22 hours at room 
temperature. Sulfur dioxide was passed through the mixture for 20 minutes 
and the mixture stirred for an additional hour. The mixture was 
concentrated and poured into 500 ml of ice. After stirring for 1 hour, the 
cold mixture was filtered, the solid was washed with cold water and dried 
in a vacuum oven at room temperature for 60 hours to give 68.8 g of 
3-chloro-2-cyano-4,4-dimethyl- 2-pentenenitrile, mp 52.degree.-53.degree.. 
In the same manner were prepared 3-chloro-2-cyano- 2-hexenenitrile, bp 
73.degree./1.2 mm; 3-chloro-2-cyano-4-methyl- 2-pentenenitrile, bp 
52.degree.-58.degree./0.3 mm; 3-chloro-2-cyano-5-methyl- 2-hexenenitrile 
(used without isolation); 3-chloro-2-cyano-4,4-dimethyl-2-heptenenitrile, 
an orange-brown liquid used as an intermediate without characterization; 
and 3-chloro-2-cyano-2-pentenenitrile, bp 57.degree.-62.degree./0.9-2.0 
mm. 
3-Amino-2-cyano-4-methyl-2-pentenenitrile 
A solution of 191.3 g of 3-chloro-2-cyano-4-methyl- 2-pentenenitrile in 300 
ml of ethanol was added slowly, maintaining the temperature below 
40.degree., during 1.3 hours, to a mixture of 800 ml of concentrated 
ammonium hydroxide and 1000 ml of ethanol. The mixture was stirred for 3 
hours, then poured over 2000 ml of ice. The solid was collected, washed 
with water and dried to obtain 122.0 g of 
3-amino-2-cyano-4-methyl-2-pentenenitrile, mp 186.degree.-188.degree.. 
In the same manner were prepared 3-amino-2-cyano-2-hexenenitrile, mp 
133.degree.-135.degree.; 3-amino-2-cyano-4,4-dimethyl-2-pentenenitrile, mp 
163.degree.-164.degree.; 3-amino-2-cyano-5-methyl-2-hexenenitrile, mp 
113.degree.-116.degree.; 3-amino-2-cyano-4,4-dimethyl- 2-heptenenitrile, 
mp 145.degree.-146.degree.; and 3-amino-2-cyano- 2-pentenenitrile, mp 
165.degree.-167.degree.. 
3-Amino-2-cyano-3-propoxypropenenitrile 
To a stirred mixture of 129.2 g of potassium tricyanomethanide, 600 g of 
propanol and 750 ml of dimethoxyethane was added dropwise 96.1 g of 
methanesulfonic acid during 45 minutes. The exothermic reaction caused the 
reaction mixture temperature to rise slightly. The volatile materials were 
removed under reduced pressure and 800 ml of hot water was added to the 
residue. The solution was treated with charcoal and filtered. The filtrate 
was evaporated to dryness under reduced pressure. When the residue was 
allowed to stand at ambient temperature, the product crystallized. The 
mother liquor from above was diluted with two volumes of ice, to give 
additional product. The total yield of 
3-amino-2-cyano-3-propoxypropenenitrile was 139 g. 
3-Amino-2-cyano-4-methyl-2-pentenethioamide 
While maintaining the temperature below 45.degree., hydrogen sulfide gas 
was passed for 2 hours into a stirred solution of 122.0 g of 
3-amino-2-cyano-4-methyl-2-pentenenitrile and 91.5 g of triethylamino in 
122 ml of pyridine. The mixture was stirred for 1 hour at room 
temperature, then was poured over 2 liters of ice. Th solid was collected, 
washed with water, dried and recrystallized from ethanol-water to give 
128.3 g 3-amino-2-cyano-4-methyl-2-pentenethioamide, mp 
112.degree.-114.degree.. 
In the same manner were prepared 3-amino-2-cyano- 
4,4-dimethyl-2-pentenethioamide, mp 129.degree.-131.degree.; 3-amino- 
2-cyano-2-hexenethioamide, mp 133.degree.-135.degree.; 3-amino-2-cyano- 
5-methyl-2-hexenethioamide (used as an intermediate without 
characterization); 3-amino-2-cyano-4,4-dimethyl- 2-heptenethioamide, mp 
132.degree.-134.degree.; and 3-amino- 2-cyano-2-pentenethioamide, mp 
104.degree.-107.degree.. 
3-Amino-2-cyano-3-propoxypropenethioamide 
A stirred mixture of 141 g of 3-amino-2-cyano-3-propoxypropenenitrile and 
94.4 g of triethylamine in 250 ml of pyridine was heated at 80.degree. for 
4 hours while hydrogen sulfide gas was continually passed through the 
mixture. Thin-layer chromatography indicated reaction to be complete. The 
reaction mixture was diluted to 2 liters with water and the pale yellow 
precipitate was collected by filtration. The precipitate was 
recrystallized from ethanol to give 114 g of 3-amino- 
2-cyano-3-propoxypropenethioamide, mp 174.degree.. 
5-Amino-4-cyano-3-isopropylisothiazole 
While maintaining the temperature below 50.degree., 86.1 g of 30% hydrogen 
peroxide was added dropwise to a solution of 128.3 g of 
3-amino-2-cyano-4-methyl- 2-pentenethioamide in 600 ml of absolute 
ethanol. The mixture was stirred at room temperature for 19 hours, 
filtered and concentrated to about half volume. Water was added to cloud 
point and the solid allowed to separate. The solid was collected and dried 
to give 123.0 g of 5-amino-4-cyano-3-isopropylisothiazole, mp 
133.degree.-135.degree.. 
In a similar manner were prepared 5-amino-4-cyano- 3-propylisothiazole, mp 
85.degree.-88.degree., 5amino-3-tert-butyl- 4-cyanoisothiazole, mp 
133.degree.-134.degree., 5-amino- 4-cyano-3-isobutylisothiazole, mp 
151.degree.-152.degree., 5-amino- 
4-cyano-3-(1,1-dimethylbutyl)isothiazole, mp 128.degree.-129.degree., 
5-amino-4-cyano-3-propoxyisothiazole, mp 122.degree.-125.degree.; and 
5-amino-4-cyano-3-ethylisothiazole, mp 148.degree.-150.degree..

EXAMPLE I 
N'-(4-Cyano-3-isobutyl-5-isothiazolyl)-N,N-dimethylchloroformamidine 
A mixture of 5.4 g of 5-amino-4-cyano-5-isobutylisothiazole and 4.9 g 
N-(dichloromethylene)-N,N-dimethylammonium chloride in 50 ml of 
chlorobenzene was placed in a flask equipped with a stirrer. A slow stream 
of nitrogen was passed through the mixture and into an absorber equipped 
to measure hydrogen chloride evolution. The mixture was heated at 
80.degree. for one hour during which time the theoretical amount of 
hydrogen chloride was evolved. The mixture was allowed to stand under 
nitrogen atmosphere at ambient temperature for 64 hours, then heated under 
nitrogen at 80.degree. for 0.5 hours. Thin-layer chromatographic analysis 
showed two sports, neither corresponding to starting material. 
The mixture was cooled to room temperature and concentrated under reduced 
pressure. The residue was triturated with pentane whereupon a solid 
formed. Both the solid and the pentane solution were found by thin-layer 
chromatography to contain both components observed in the product. The 
pentane was removed under reduced pressure and the residue dissolved in 
cyclohexane. The cyclohexane solution was subjected to chromatographic 
separation using a 1.25.times. 18 inch column containing 100 g of silica 
gel. Using an eluting solvent containing progressively higher proportion 
of ethyl acetate, fifty-six 40-ml fractions of eluate were collected. 
Cuts 1-10 showed no spot in thin-layer chromatography; cuts 11-13 showed 
one spot; cuts 14-25 showed two spots; cuts 26-35 showed only one spot. 
The product from cuts 11-13 was found by mass spectrographic analysis to 
correspond closely to a dimer of 
4-cyano-5-[(dimethylamino)-methyleneamino] -3-isobutylisothiazole. The 
product, 1.4 g, from cuts 26-35 was found by elemental analysis and ir and 
nmr spectral analysis to be the desired N'-( 
4-cyano-3-isobutyl-5-isothiazolyl)-N,N-dimethylchloroformamidine, m.p. 
79.degree.-80.degree.. 
Analysis: Calc'd for C.sub.11 H.sub.15 ClN.sub.4 S: C, 48.79; H, 5.58; Cl, 
13.09; N, 20.69; S, 11,84; Found: C, 48.88; H, 5.70; Cl, 13.15; N, 20.99; 
S, 12.57. 
EXAMPLE II 
N'-(4-Cyano-3-isopropyl-5-isothiazolyl)-N,N-dimethylformamidine 
To a solution of 6.7 g of 5-amino-4-cyano-3-isopropylisothiazole in 30 ml 
of dimethylformamide was slowly added 10.4 ml of thionyl chloride and the 
mixture was heated under reflux for 3 hours. The mixture was poured into 
300 ml of water and the water-dimethylformamide was removed under reduced 
pressure. The residue was dissolved in ethanol. The solution was treated 
with decolorizing charcoal, then was diluted with 300 ml of water. The 
small amount of solid which separated was removed by filtration and was 
discarded. As the solution stood undisturbed, tan solid separated which 
was collected and recrystallized from methylcyclohexane to give 3.0 g of 
N'-(4-cyano-3-isopropyl-5-isothiazolyl)-N,N-dimethylformamidine, m.p. 
95.degree.-97.degree.. A small amount was sublimed at 120.degree. under 
0.03 mm without change in melting point. The nmr spectrum was consistent 
with the assigned structure. 
Analysis: Calc'd for C.sub.10 H.sub.14 N.sub.4 S: C, 54.03; H, 6.35; N, 
25.20; S, 14.42; Found: C, 54.25; H, 6.56; N, 25.25; S, 14.59. 
EXAMPLE III 
N'-(4-Cyano-3-propoxy-5-isothiazolyl)-N,N-dimethylformamidine 
A mixture of 13.7 g of methanesulfonyl chloride in 25 ml of 
dimethylformamide was stirred at room temperature for about 16 hours. Into 
the mixture was stirred 11 g of 5-amino-4-cyano-3-propoxyisothiazole which 
addition caused an exothermic reaction. The mixture was concentrated under 
reduced pressure and the residue was recrystallized from ethanol to give 
2.7 g of crystalline 
N'-(4-cyano-3-propoxy-5-isothiazolyl)-N,N-dimethylformamidine, m.p. 
117.degree.-118.degree.. The nmr spectrum was consistent with the assigned 
structure. 
Analysis: Calc'd for C.sub.10 H.sub.14 N.sub.4 OS: C, 50.40; H, 5.92; N, 
23.51; Found: C, 50.66; H, 6.09; N, 23.45. 
EXAMPLE IV 
N'-(4-Cyano-3-(1,1-dimethylbutyl)-5-isothiazolyl)-N,N-dimethylformamidine 
A solution of 25 g of 5-amino-4-cyano-3-(1,1-dimethylbutyl)isothiazole and 
35.6 g of triethyl orthoformate in 200 ml of dioxane was heated under 
reflux for two hours. To the solution was added 24.5 g of acetic anhydride 
and the mixture was heated under reflux an additional 20 hours. The 
mixture wss concentrated under reduced pressure and the residue was 
distilled in a short path still at 120.degree. under 0.1 mm Hg to give 
31.8 g of 4-cyano-3-(1,1-dimethylbutyl)-5-[N-(ethoxymethylene)amino] 
isothiazole which was dissolved in 125 ml of ethanol, without further 
purification. The ethanolic solution was placed in a flask equipped with a 
gas inlet tube and one outlet of which was closed by a small rubber 
balloon. Dimethylamine gas was passed into the solution until the balloon 
remained inflated; during the introduction of dimethylamine, the 
temperature of the mixture increased to 60.degree.. The reaction mixture 
was concentrated under reduced pressure. The residue was recrystallized 
from a mixture of diethyl ether (90 parts) and pentane (10 parts) at low 
temperature to give 26.5 g of 
N'-[4-cyano-3-(1,1-dimethylbutyl)-5-isothiazolyl]-N,N-dimethylformamidine, 
m.p. 65.degree.-67.degree.. The nmr spectrum was consistent with the 
assigned structure. 
Analysis: Calc'd for C.sub.13 H.sub.20 N.sub.4 S: C, 59.06; H, 7.63; N, 
21.19; S, 12.13; Found: C, 59.06; H, 7,87; N, 21.06; S, 12.40. 
EXAMPLE V 
N'-(4-Cyano-3-propoxy-5-isothiazolyl)-N,N-dimethylchloroformamidine 
A mixture of 11 g of 5-amino-4-cyano-3-propoxyisothiazole and 9.8 g of 
N-(dichloromethylene)-N,N-dimethylammonium chloride in 80 ml of 
dischloromethane was heated under reflux for about 18 hours. The mixture 
was concentrated under reduced pressure and the residue was slurried with 
aqueous sodium bicarbonate solution. The solid was recrystallized from 
ethanol, then from methylcyclohexane to give 11.3 g of 
N'-(4-cyano-3propoxy-5-isothiazolyl)-N,N-dimethylchloroformamidine, m.p. 
98.degree.-108.degree.. The nmr spectrum was consistent with the assigned 
structure. 
Analysis: Calc'd for C.sub.10 H.sub.13 ClN.sub.4 OS: C, 44.04; H, 4.80; Cl, 
13.00; N, 20.54; S. 11.75; Found: C, 45.16; H, 4.78; Cl, 13.01; N, 21.10; 
S, 11.88. 
EXAMPLE VI 
N'-(4-Cyano-3-isopropyl-5-isothiazolyl)-N,N-dimethylchloroformamidine 
A stirred mixture of 16.7 g of 5-amino-4-cyano-3-isopropylisothiazole and 
16.2 g of N-(dichloromethylene)-N,N-dimethylammonium chloride in 100 ml of 
dichloromethane was heated under reflux during 20 hours. Thin-layer 
chromatographic analysis of the reaction mixture indicated that reaction 
was complete. The dichloromethane solvent was evaporated under reduced 
pressure. To the residue was added 100 ml of saturated sodium bicarbonate 
solution and 50 ml of ethanol. This mixture was extracted with three 60 ml 
portions of dichloromethane. The combined extracts were dried over a 
mixture of anhydrous sodium sulfate and anhydrous magnesium sulfate. The 
mixture was filtered and the filtrate was evaported under reduced 
pressure. The residue was washed with 90 ml of diethyl ether followed by a 
wash with 10 ml of pentane. The precipitate, mp 70.degree.-72.degree., was 
collected by filtration. Diethyl ether:pentane (1:1) was added to the 
filtrate. The filtrate was dried with magnesium sulfate. The mixture was 
filtered, and the filtrate cooled in an external dry-ice acetone bath, to 
yield a second crop of solid mp 65.degree.-67.degree.. The combined 
solids were recrystallized from hexane to yield 13.3 g of 
N'-(4-cyano-3-isopropyl-5-isothiazolyl)-N,N-dimethylchloroformamidine, mp 
72.degree.-75.degree.. The nmr and ir spectra were consistent with the 
assigned structure. 
Analysis: Calc'd for C.sub.10 H.sub.13 N.sub.4 ClS: C, 46.78; H, 5.10; N, 
21.82; Found: C, 46.73; H, 5.25; N, 21.86. 
In this manner, subsequent runs produced 38.2 g, 133.7 g and 176 g 
respectively of the chloroformamidine. 
EXAMPLE VII 
N'-(4-Cyano-3-isopropyl-5-isothiazolyl)-N,N-dimethylfluoroformamidine 
A mixture of 12.8 g of 
N'-(4-cyano-3-isopropyl-5-isothiazolyl)-N,N-dimethylchloroformamidine, 2.9 
g of potassium fluoride and a catalytic amount of 2,3,11,12 
-dibenzo-1,4,7,10,13,16-hexaoxacyclooctadeca-2,11-diene, in 60 ml of 
acetonitrile was stirred at ambient temperature for 12 hours. The reaction 
mixture was filtered and the filtrate was evaporated under reduced 
pressure. The residue was recrystallized from diethyl ether to give 2.5 
grams of 
N'-(4-cyano-3-isopropyl-5-isothiazolyl)-N,N-dimethylfluoroformamidine, mp 
100.degree.-102.degree.. The nmr and ir spectra were consistent with the 
assigned structure. 
Analysis: Calc'd for C.sub.10 H.sub.13 N.sub.4 FS: C, 49.98; H, 5.45; N, 
23.32; Found: C, 50.15; H, 5.51; N, 23.29. 
EXAMPLE VIII 
N'-(4Cyano-3-isopropyl-5-isothiazolyl)-N,N-dimethylcyanoformamidine 
In the manner of Example VII, 7 g of N'-(4-cyano- 
3-isopropyl-5-isothiazolyl)-N,N-dimethylchloroformamidine, 3.6 g of 
anhydrous potassium cyanide, and a catalytic amount of 
2,3,11,12-dibenzo-1,4,7,10,13,16-hexaoxacycloocta- 2,11-diene in 200 ml of 
dry aceto-nitrile were allowed to react for several days. After solvents 
were removed under reduced pressure, the residue was recrystallized from 
methylcyclohexane to yield 4.3 g of 
N'-(4-cyano-3-isopropyl-5-isothiazolyl)-N,N-dimethylcyanoformamidine, mp 
78.degree.-79.degree.. The ir and nmr spectra were consistent with the 
assigned structure. 
Analysis: Calc'd for C.sub.11 H.sub.13 N.sub.5 S: C, 53.42; H, 5.30; N, 
28.32; S, 12.96; Found: C, 52.99; H, 5.39; N, 27.92; S, 12.58. 
EXAMPLE IX 
N'-(4-Cyano-3-propyl-5-isothiazolyl)-N,N-dimethylchloroformamidine 
In the manner of Example VI, a solution of 8.4 g of 
5-amino-4-cyano-3-propylisothiazole in 50 ml of dichloromethane was 
treated with 9.8 g of N-(dichloromethylene)-N,N-dimethylammonium chloride. 
After removal of the volatile materials under reduced pressure, the 
residue was recrystallized from 90:10 hexane:benzene to yield 6.5 g of 
N'-(4-cyano-3-propyl-5-isothiazolyl)-N,N-dimethylchloroformamidine, mp 
108.degree.-109.degree.. The ir and nmr spectra were consistent with the 
assigned structure. 
Analysis Calc'd for: C.sub.10 H.sub.13 ClN.sub.4 S: C, 46.78; H, 5.10; Cl, 
13.81; N, 21.82; S, 12.49; Found: C, 46.92; H, 5.26; Cl, 13.59; N, 21.59; 
S, 12.22. 
EXAMPLE X 
N'-(3-tert-Butyl-4-cyano-5-isothiazolyl)-N,N-dimethylchloroformamidine 
In the manner of Example VI, 9.1 g of 5-amino-3-tert-butyl- 
4-cyanoisothiazole and 9.8 g of N-(dichloromethylene)-N,N-dimethylammonium 
chloride were allowed to react in 50 ml of dichloromethane. The volatile 
materials were evaporated under reduced pressure. The residue was 
recrystallized from hexane to give 9.2 g of N'-(3-tert-butyl-4 
-cyano-5-isothiazolyl)-N,N-dimethylchloroformamidine, mp 
94.degree.-100.degree.. The ir and nmr spectra were consistent with the 
assigned structures. 
Analysis Calc'd for: C.sub.11 H.sub.15 ClN.sub.4 S: C, 48.79; H, 5.58; Cl, 
13.09; N, 20.69; S, 11.84; Found: C, 49.05; H, 5.66; Cl, 12.90; N, 20.92; 
S, 11.78. 
EXAMPLE XI 
N'-(4-Cyano-3-isopropyl-5-isothiazolyl)-N,N-dimethylbromoformamidine 
To a solution of 22.8 g of N'-(4-cyano-3-isopropyl- 
5-isothiazolyl)-N,N-dimethylurea in 300 ml of benzene was added 83.3 g of 
phosphorous oxybromide. The solution was cooled to 0.degree. and 14 ml 
(9.7 g) of triethylamine was added. The ice-bath was removed and the 
reaction mixture was heated under reflux overnight. The following day the 
reaction mixture was filtered through sintered glass. The filtrate was 
washed with two 200 ml portions of cold water and two 200 ml portions of 
saturated sodium bicarbonate solution. Two hundred milliliters of 
chloroform was added to aid in separation of the organic phase from the 
final wash. The separated organic phase was dried, then concentrated under 
reduced pressure. The residue was passed over a column of 300 grams of 
silica gel with chloroform as the eluant. The first ten 250 ml fractions 
were evaporated to produce a yellow solid, mp 93.degree.-97.degree.. The 
combined residues were recrystallized from 175 ml of cyclohexane to yield 
13.8 g of N'-(4 
-cyano-3-isopropyl-5-isothiazolyl)-N,N-dimethylbromoformamidine mp 
92.degree.-96.degree.. The ir and nmr spectra were consistent with the 
assigned structure. 
Analysis Calc'd for: C.sub.10 H.sub.13 BrN.sub.4 S: C, 39.87; H, 4.35; Br, 
26.53; N, 18.60; S, 10.64; Found: C, 39.62; H, 4.40; Br, 26.37; N, 18.53; 
S, 10.68. 
EXAMPLE XII 
N'-(4-Cyano-3-ethyl-5-isothiazolyl)-N,N-dimethylchloroformamidine 
In the manner of Example VI, 7.6 g of 5-amino-4 -cyano-3-ethylisothiazole 
and 8.1 g of N-(dichloromethylene) -N,N-dimethylammonium chloride were 
allowed to react in 100 ml of dichloromethane. The volatile materials were 
evaporated under reduced pressure. The residue was recrystallized twice 
from cyclohexane to give 2.0 g of 
N'-(4-cyano-3-ethyl-5-isothiazolyl)-N,N-dimethylchloroformamidine, mp 
95.degree.-97.degree.. The nmr spectrum was consistent with the assigned 
structure. 
Analysis Calc'd for: 
C.sub.9 H.sub.11 N.sub.4 ClS: C, 44.53; H, 4.57; Cl, 14.61; N, 23.08; S, 
13.21; Found: C, 44.59; H, 4.48; Cl, 14.69; N, 23.06; S, 13.03. 
The herbicidal activities of the compounds of this invention were 
demonstrated as follows. In preemergence tests, rows of seeds of lima 
beans (Phaseolus lunatus), corn (Zea mays), wild oats (Avena fatua), 
lettuce (Lactuca sativa), mustard (Brassica juncea) and crabgrass 
(Digitaria sanguinalis) were planted in shallow flat-bed trys (20 
cm.times. 15 cm.times. 7.5 cm) containing 5 cm to 7.5 cm of sandy loam 
soil. Within 24 hours after planting, an aqueous acetone solution of the 
compound (using sufficient acetone to obtain solution) was sprayed on the 
soil at a rate equivalent to 8.96 kilograms per hectare, 4.48 kg, 2.24 kg, 
0.56 kg, and 0.28 kg/hectare, using a total volume equivalent to 760 
liters per hectare. The trays were maintained under normal growing 
conditions in the greenhouse for about 3 weeks, after which the herbicidal 
efficacy of the compound was assessed. Individual plant species were 
examined in comparison with untreated plants. Table 1 lists data collected 
in preemergence tests with compounds of the present invention. 
In postemergence tests, rows of seeds were planted as for preemergence 
tests and the untreated flats were maintained in the greenhouse until the 
first trifoliate leaves of the bean plants were unfolding. The test plants 
were then sprayed with an aqueous acetone solution of the compound as for 
preemergence tests. The plants were returned to the greenhouse and held 
under normal growing conditions for about 3 more weeks, after which the 
herbicidal efficacy of the compound was assessed. Table 2 lists data 
collected in postemergence tests with compounds of the present invention. 
An evaluation of the preemergence herbicidal activity of the compound of 
Example VI was carried out employing a broader range of plants. The 
techniques utilized were as described for the preemergence tests above. 
Results are collected in Table 3. 
Table 1 
______________________________________ 
Preemergence Herbicidal Activity 
of Isothiazolylformamidines 
(expressed as % kill at indicated rate in kg/hectare) 
Compound 
of Lima Wild Mus- Crab- 
Example Rate Beans Corn Oats Lettuce 
tard grass 
______________________________________ 
I 2.24 100 0 50 100 100 100 
1.12 100 0 30 100 100 80 
0.56 0 0 0 70 80 30 
0.28 0 0 0 50 70 0 
II 8.96 100 0 10 100 100 30 
4.48 100 0 70 100 100 0 
2.24 100 0 30 100 80 0 
1.12 100 0 60 100 100 0 
0.56 100 0 40 100 50 50 
0.28 100 0 30 100 20 0 
III 8.96 0 0 0 30 0 0 
4.48 0 0 0 0 0 0 
2.24 0 0 0 0 0 0 
1.12 0 0 0 0 0 0 
0.56 0 0 0 0 0 0 
0.28 0 0 0 0 0 0 
IV 8.96 0 0 50 0 50 0 
4.48 0 0 0 0 0 0 
2.24 0 0 0 0 0 0 
1.12 0 0 0 0 0 0 
0.56 0 0 0 0 0 0 
0.28 0 0 0 0 0 0 
V 8.96 100 0 0 100 100 0 
4.48 75 0 0 30 0 0 
2.24 0 0 0 0 0 0 
1.12 0 0 0 0 0 0 
0.56 0 0 0 0 0 0 
0.28 0 0 0 0 0 0 
VI 8.96 100 100 100 100 100 100 
4.48 100 100 80* 100 100 100 
2.24 100 0 80 100 100 30 
1.12 100 0 70 100 100 10 
0.56 100 0 50 90* 100 0 
0.28 100 0 30 90* 100 0 
VII 8.96 100 30 90* 100 100 90* 
4.48 100 0 25 100 100 90* 
2.24 100 0 50 100 100 80 
1.12 100 0 0 75 90* 20 
0.56 0 0 0 0 0 0 
0.28 -- -- -- -- -- -- 
VIII 8.96 100 0 100 100 100 95* 
4.48 100 0 100 100 100 20 
2.24 90* 0 30 100 100 20 
1.12 90* 0 20 100 100 0 
0.56 20 0 0 90* 80 0 
0.28 0 0 0 40 75 0 
IX 8.96 100 100 100 100 100 95* 
4.48 100 90* 100 100 100 95* 
2.24 100 0 100 100 100 95* 
1.12 95* 0 95* 100 100 95* 
0.56 100 0 95* 100 95* 0 
0.28 40 0 0 90* 0 0 
X 8.96 100 100 100 100 100 95* 
4.48 100 95* 100 100 100 95* 
2.24 100 30* 100 100 100 95* 
1.12 100 0 100 100 100 50 
0.56 100 0 30 100 100 0 
0.28 100 0 0 40 95* 0 
XI 8.96 100 70 100 100 100 100 
4.48 100 0 100 100 100 100 
2.24 100 0 100 100 100 100 
1.12 100 0 70 100 100 100 
0.56 100 0 20 100 50 100 
0.28 75 0 0 100 100 50 
XII 8.96 100 70* 100 100 100 100 
4.48 100 30* 100 100 100 100 
2.24 100 0 100 100 100 100 
1.12 100 0 100 100 100 80 
0.56 100 0 70 100 100 50 
0.28 100 0 50 100 100 100 
______________________________________ 
*Plants not dead were severely damaged and not expected to live. 
Table 2 
______________________________________ 
Postemergence Herbicidal Activity 
of Isothiazolylformamidines 
(expressed as % kill at 8.96 kg/hectare) 
Compound of 
Lima Wild Crab- 
Example Beans Corn Oats Lettuce 
Mustard 
grass 
______________________________________ 
I 100 30 100 100 100 100 
II 100 0 10 100 100 10 
III 0 0 0 0 0 0 
IV 0 0 0 100 100 0 
V 50 0 0 100 50 0 
VI 100 100 100 100 100 100 
VII 100 75 100 100 100 90* 
VIII 100 0 100 100 100 90* 
IX 100 60* 100 100 100 95* 
X 100 0* 100 100 100 95* 
XI 100 100 100 100 100 100 
XII 100 100 100 100 100 100 
______________________________________ 
*Plants not dead were severely damaged and not expected to live. 
Table 3 
______________________________________ 
Preemergence Herbicidal Activity 
of Isothiazolylformamidine of Example VI 
(expressed as % kill at indicated rate 
in kg/hectare) 
0.28 0.56 1.12 2.24 4.48 
______________________________________ 
Corn 0 0 0 70 100 
Morning Glory 
90* 100 100 100 100 
Morning Glory 
100 50* 60* 50* 50* 
Giant Foxtail 
0 20 100 100 100 
Giant Foxtail 
40 70 100 100 100 
Crabgrass 0 30 70* 100 100 
Crabgrass 0 100 100 100 100 
Barnyardgrass 
50 80 90* 95* 90* 
Barnyardgrass 
30 80* 100 100 100 
Soybean 100 100 100 100 100 
Wheat 30 50 100 100 100 
Barley 30 50 100 100 100 
Prickly Sida 
-- 50 100 100 100 
Sugar Beet 
70 100 100 100 100 
Flax 0 0 70 100 100 
Peanut 0 0 100 100 100 
Sicklepod 30 70 100 100 100 
Downy Brome 
50 50 90* 100 100 
Coffeeweed 
100 100 100 100 100 
Tomato 0 0 100 100 100 
Sorghum 0 0 30 70* 100 
Oats 70* 100 100 100 100 
Rice 100 100 100 100 100 
Cotton 75 100 100 100 100 
Purple Nutsedge 
0 0 0 0 25 
______________________________________ 
*Plants not dead were severely damaged and not expected to live. 
For herbicidal application, the compounds of this invention may be utilized 
in diverse formulations including the agricultural adjuvants and 
agricultural carriers, i.e. those materials normally employed to 
facilitate the dispersion of active ingredients in agricultural 
applications, recognizing the fact that the formulation and mode of 
application of a toxicant may affect the activity of the material in a 
given application. Thus, a compound of this invention may be formulated as 
a granule of relatively large particle size, as a wettable powder, as an 
emulsifiable concentrate, as a solution, or as any of several other known 
types of formulations, depending on the desired mode of application. 
Granular formulations are particularly useful for aerial distribution or 
for penetration of a canopy of foiliage. Useful granular formulations may 
be of several types. Impregnated granules are those wherein the active 
ingredient is applied to large particles of an absorbent carrier, such as 
an attapulgite or kaolin clay, corncobs, expanded mica, and so forth, 
normally in the form of a solution is a solvent. Surface-coated granules 
may be produced by spraying the molten active ingredient onto the surface 
of a generally non-absorbent particle or by spraying on a solution of 
active ingredient in a solvent. The core may be water-soluble such as a 
prilled fertilizer, or insoluble such as sand, marble chips or coarse 
talc. Particularly useful is a granule wherein a wettable powder is 
applied as a surface coating to a sand or other insoluble particle such 
that the wettable powder may be dispersed on contact of the granule with 
moisture. Granules may be produced by agglomeration of dusts of powders by 
compaction rollers, by extrusion through a die or by use of a granulating 
disc. Granular formulations may vary widely in concentration, with useful 
formulations containing as little as 0.5% or as much as 95% of active 
ingredient. 
Wettable powders, also useful formulations for both pre- and postemergence 
herbicides, are in the form of finely divided particles which disperse 
readily in water or other dispersants. The wettable powder is ultimately 
applied to the soil or to the undesired plant growth either as a finely 
divided dry material or as an emulsion in water or other liquid. Typical 
carriers for wettable powders include fuller's earth, kaolin clays, 
silicas and other highly absorbent, readily wet inorganic diluents. 
Wettable powders normally are prepared to contain about 5% to 80% of 
active ingredient, depending on the absorbency of the carrier, and usually 
also contain a small amount of a wetting, dispersing or emulsifying agent 
of factilitate dispersion. For example, a useful wettable powder 
formulation contains 80.8 parts of N'-(4-cyano-3-isopropyl-5-isothiazolyl) 
-N,N-dimethylformamidine, 17.9 parts of palmetto clay, and 1.0 part of 
sodium lignosulfonate and 0.3 part of sulfonated aliphatic polyester as 
wetting agents. 
Other useful formulations for herbicidal applications are the emulsifiable 
concentrates, which are homogeneous liquid or paste compositions 
dispersible in water or other dispersant, and may consist entirely of a 
compound of this invention with a liquid or solid emulsifying agent, or 
may also contain an agriculturally acceptable liquid carrier, such as 
xylene, heavy aromatic naphthas, isophorone and other nonvolatile organic 
solvents. 
Typical wetting, dispersing or emulsifying agents used in agricultural 
formulations include, for example, the alkyl and alkylaryl sulfonates and 
sulfates and their sodium salts; polyethylene oxides; sulfonated oils; 
fatty acid esters of polyhydric alcohols; and other types of 
surface-active agents, many of which are available in commerce. The 
surface-active agent, when used, normally comprises from 1% to 15% by 
weight of the herbicidal composition. 
These formulations may be applied without further dilution or as dilute 
solutions, emulsions or suspensions in water or other suitable diluent. 
The compositions may be applied to the area wherein control is desired by 
spraying onto the undesired vegetation or onto the surface of the soil in 
the case of liquid compositions or by distribution from mechanical 
equipment in the case of solids. The surface-applied material may also be 
blended into the upper layer of soil by cultivation, or left as applied, 
as is appropriate to gain the optimum results with the particular 
treatment. 
The active herbicidal compounds of this invention may be formulated and/or 
applied with insecticides, fungicides, nematicides, plant regulators, 
fertilizers, and other agricultural chemicals. In applying the active 
compounds of this invention, whether formulated alone or with other 
agricultural chemicals, an effective amount and concentration of 
isothiazolyl compound is of course employed. 
It is apparent that various modifications may be made in the formulation 
and application of the novel compounds of this invention, without 
departing from the inventive concept herein, as defined in the following 
claims: