CA1059520A - S-triazolo (5,1-b) benzothiazoles - Google Patents

Abstract

Abstract of the Disclosure Novel s-triazolo (5,1-B) benzolthiazoles are des-cribed herein which are useful for the control of fungi which attack the foliage of plants. These novel compounds are prepared by cyclizing of 3-amino-2-iminobenzothiazolines, 3-amino-2-acyliminobenzothiazolines or 3-acylamino-2-imino-benzothiazolines and have the structural formula I
wherein R is hydrogen, hydroxy or methyl and R1 is methyl, ethyl, chloro, fluoro or methoxy, with the methoxy R1 group occupying only the 5-position.

Description

~(~595ZO

s-TRIAZOLO~5,1-b~BENZOTHI~ZOLES
This invention relates to the field of agricul-tural chemistry, and provides to the art new compounds which control phytopathogens.
Agricultural chemistry has long attempted to improve on existing fungicides. Many classes of organic compounds have been used, and new compounds are constantly being made and evaluated. Some o~ the prior art which may be relevant to the present invention is discussed below.
Dreikorn, U.S. Patents 3,764,681 and 3,839,569, disclosed the fungicidal efficacy of tetrazolo[l,5-a3quino-lines and s-triazolo[4,3-a]quinolines. sel~ian Patent ~;
803,098 and West German Offenlegungsschrift 2,249,350 dis-closed that certain imidazoquinoxalines are also useful as agricultural fungicides.
Tamura et al., "Novel Syntheses of Thiazolo[3,2-b]-s-Triazoles, J. Hetero. Chem. X, 947-51 (1973), published February 16, 1974, disclosed a similar compound having no substituent on the phenyl ring.
Potts et al., "Synthesis of the Thiazolo[2,3-c]-s-Triazole and the Thiazolo[3,2-b~-s-Triazole Systems", J.
. Chem. 36, 10-13 (1971), and Japanese Patent 71 26,500, C.A. 75, 140863(~) (1971), disclosed thiazolo[3,2-b]-s-triazoles, which were said to be useful as bactericides and agricultural chemicals.
Mosby et al., U. S~ Patent 3,389,137, showed a tetrazolo[5,1-b]benzothiazole, which was described only as an intermediate to phosphene imide compounds.

X-4326 -2- ' ; ~ - . , , . . : :

lVS~ZO

The compounds of this invention are of the general formula R1 ~ R

wherein R is hydrogen, hydroxy or methyl; and Rl is methyl, e~hyl, chloro, fluoro, or methoxy; and provided that the methoxy Rl group occupies only the 5-position.
The compounds of formula (I) are prepared by reacting a compound of the general formula R'~

wherein Rl is defined as before, with a cyclizing agent.
The compounds of formula (I) are preferably pre-pared by reacting a compound of the general formula N C R~
, R ~ ll I (III) NH

wherein Rl is defined as before; and R2 is methyl, methoxy, or hydrogen, with a cyclizing agent.

' ~. . . .
., . : .
. . .
;. . - . .
.

l~S9SZO

Also, the isomer of formula IIII) can be reacted in a similar manner to provide the compounds of fo~mula (I).
This isomer has the general formula ~ \ / \
NI~ -r~ (IV) ~-/ O

wherein Rl and R2 are defined as before.
A preferred group of compounds comprises the compounds of formula (I) wherein R is hydrogen.
The preferred Rl substituents are methyl, chloro and fluoro, and the preferred location for the Rl substi-tuents is the 5-position.
The compounds below are typical of the compounds of formula (I).
6-chloro-s-triazolo[5,1-b]benzothiazole 7-fluoro-2-hydroxy-s-triazolo[5,1-b]benzothiazole . 6-ethyl-s-triazolo[5,1-b]benzothiazole : , 20 7-ethyl-2-hydroxy-s-triazolo[5,1-b]benzothiazole ' ~ 5-methoxy-2-hydroxy-s-triazolo[S,l-b]benzothia-.' zole . 7-chloro-s-triazolo[5,1-b~benæothiazole .:
8-fluoro-s-triazolo[5,1-b]benzothiazole 7-ethyl-2-methyl-s-triazolo~5,1-b]benzothiazole The preferred compounds of formula (I) are 5-` methyl-s-triazolo[5,1-b]benzothiazole, 5-fluoro-s-tria-zolo[5,1-b]benzothiazole, 5-chloro-s-triazolo[5,1-b]benzo-thiazole, 5-methoxy-s-triazolo[5,1-b]benzothiazole, and

2,5-dimethyl-s-triazolo[5,1-b]benzothiazole.

1.~5~520 The compounds of formula (I) are made from 2-aminobenzothiazoles, which are readily obtained. ~he Rl substituents of the compounds are provided by corresponding substituents on the starting ~-aminobenzothiazoles.
Various processes for the synthesis of the new compounds can be used. Tamura, cited above, taught a process which began with the preparation of 3-amino-2-iminobenzothiazoline, which he described as a 2,3-diamino compound, by the reaction of the 2-aminobenzothiazole compound with O-mesitylenesulfonylhydroxylamine at ice bath temperature in methylene dichloride. The amino-imino compound, produced as the mesitylene sulfonate salt, was refluxed with acetic anhydride to produce 2-methyl-s-triazolo[5,1-bJbenzothiazole in 80 percent yield.
The Tamura process is functional, but produces the - 2-acetylamino-3-acetylimino compound as a side product.
The best route for the preparation of the com-pounds of formula (I) wherein R is methyl proceeds by the cyclization with polyphosphoric acid of an intermediate 2-alkanoylimino-3-aminobenzothiazoline of formula (III).
The compounds named below are typical of the compounds of formula (III).
2-acetylimino-3-amino-6-chlorobenzothiazoline

3-amino-7-ethyl-2-methoxycarbonyliminobenzothia-zoline ~ X-4326 -5-`` ~QS9SZO

2-acetylimino-3-amino-4-methoxybenzothiazoline 2-acetylimino-3-amino-6-fluorobenzothiai~line 2-acetylimino 3-amino-S~chlorobenzothiazoline 3-amino-4-ethyl-~-methoxycarbonyliminobenzothia-zoline 2-acetylimino-3-amino-4-fluorobenzothiazoline 2-acetylimino-3-amino-6-ethylbenzothiazoline 3-amino-4-methoxy-2-methoxycarbonyliminobenzo-thiazoline The intermediate is prepared by the reaction with O-mesitylenesulfonylhydroxylamine of a 2-aminobenzothiazole, in an aromatic solvent or a halogenated solvent such as methylene dichloride at a temperature from the freezing point of the reaction mixture to room temperature, pre-ferably ice bath temperature, to produce a 3-amino-2-imino compound as the mesitylene sulfonate salt. The salt is converted to the free base by treatment with a strong base, and the free base reacted with acetyl halide to produce the acylated intermediate. The acylation is done at the same temperature as the amination step in an aromatic, alkane or halogenated solvent, or in an ether such as tetrahydrofuran, in the presence of an acid scavenger such as txiethylamine, or other tertiary amines, or a strong inorganic base such as an alkali metal carbonate.
The amination step described above, using O-mesitylenesulfonylhydroxylamine can also be done using one of the following amining agentsJchloramine, _-bromo-phenylsulfonylhydroxylamine, p-toluenesulfonylhydroxyl-amine, methanesulfonylhydroxylamine, and phenylsulfonyl-` 30 hydroxylamine.

~ . , . ~. , ., : .

l~:)S95'~0 The cyclization of the intermediate is carried outin neat polyphosphoric acid. rrhe reaction goes mo~ ef-ficiently at relatively high temperatures such as from 10~
to 120~C., at which temperatures the reaction goes in good yields in about 1 to 2 hours.
The compounds of formula (I) wherein R is hydro-gen are conveniently made by cyclizing an intermediate 3-amino-2-iminobenzothiazoline of formula (II) with tri-ethylorthoformate in an inert reaction solvent. Xylene is the preferred solvent, but other aromatic solvents are also useful. The mixture is heated slowly, and the ethanol released by the reaction should be removed by the use of a Dean-Stark trap or a similar device on the reaction flask.
Compounds having a 2-methyl qroup can be made in the same way by using triethylorthoacetate or a mixed anhydride in place of triethylorthoformate.
Compounds wherein R is hydrogen are also made by cyclizing the amino-imino salt intermediate with neat formic acid at reflux temperature for 12-24 hours.
The compounds wherein R is hydroxy are made by the cyclization of a 2-methoxycarbonylimino-3-aminobenzothia-zoline of formula (III). The intermediate is produced by acylating a 3-amino-2-imino compound with chloroformic acid methyl ester, in the usual fashion. The intermediate is cyclized either thermally, at the melting point neat, or by treatment with an alkali metal hydride in an inert solvent such as an ether, an alkane, or an aromatic solvent, pre-ferably tetrahydrofuran, at reflux temperature.

.

~)59~20 Another useful method of synthesis for the com-pounds of formula (I) begins with a l-acyl-2-phen~'hydra-zine, which is reacted with an alkali metal thiocyanate in an aromatic solvent at an elevatod temperature from 40C. to reflux temperature. The intermediate product is a 4-acyl-3-phenylthiosemicarbazide, which is cyclized with bromine in a halogenated solvent at a temperature from about 30C. to the reflux temperature of the reaction mixture to produce a 3-acylamino-2-iminobenzothiazoline as the HBr salt. The salt is reduced to the free base of formula (IV) by contact with a strong base as described above, and is cyclized by heating at the reflux temperature in acetic acid to produce the desired product. Other reagents which could be used in place of the acetic acid are sulfuric acid, heat, and acetic anhydride.
The following preparative examples illustrate the synthetic methods used in preparing the starting compounds of formulae II, III and IV.
Example A
A 7.2 g. portion of 2-amino-4-methoxybenzothiazole ,~
was slurried 1n methylene dichloride. The mixture was cooled in an ice bath, and an 11 g. portion of mesitylene-sulfonylhydroxylamine was added, as a methylene dichloride solution at ice kath temperature. The reaction mixture was ~ ;
allowed to warm gradually to room temperature over a three-hour period. The reaction mixture was then diluted with ethyl ether and filtered.
The solids were slurried in 100 ml. of chloroform.
A solution of 6 g. of KOH in 75 ml. of water was added over lOS9$20 a 30-minute period. The solid crude product was separated by filtration, and the chloroform layer was evapor~ted to dryness under vacuum to produce more product. The products were combined and recrystallized from ethyl acetate to produce 4.8 g. of 3-amino-2-imino-4-methoxybenzothiazoline, m.p. 131 32C., which was identified by nuclear magnetic resonance analysis.
Example s A 1.7 ~. portion of 3-amino-2 imino-4-methyl-benzothiazoline was dissolved in about S0 ml. of tetra-hydrofuran, and l.l g. of triethylamine was added. The reaction mixture was cooled in an ice bath, and l g. of acetyl chloride, dissolved in 2 ml. of tetrahydrofuran, was added dropwise while the mixture was stirred; After the addition was complete, the reaction mixture was stirred at ice bath temperature for about 8 hours, and was then diluted with an equal volume of water. The tetrahydrofuran was removed under vacuum, and the remaining aqueous mixture was ! filtered to recover the product. After recrystallization from ethanol, the yield of purified product was 2.0 g. of 3-amino-4-methyl-2-acetyliminobenzothiazoline, m.p. 154-5C. The product was identified by nuclear magnetic resonance and ultraviolet analysis and by elemental micro-analysis.
Theoretical Found C 54.28% 54.59 ! H 5.01 5.42 N 18.99 18.11 ' .
.

~055~20 Example C
A 1.8 g. portion of 3-amino-2-imino-4-m~thyl-ben~othiazoline was s~urried in about 50 ml. of tetra-hydrofuran, and 1.3 g. of triethylamine was added. The reaction ~ixture was then cooled in an ice bath, and 1.04 g. of chloroformic acid methyl ester was added dropwise.
The reaction mixture was stirred at ice bath temperature for about 4 hours after complet on of the addition, and the reaction mixture was then worked up as described in Example B. The product was identified as 3-amino-2-methoxycarbonylimino-4-methylbenzothiazoline by nuclear magnetic resonance and ultraviolet analysis, and by elemental microanalysis as follows:
Theoretical Found C50.26% 50.86 H 4.67 4.91 N 17.71 17.66 ;~
Example D
.
The reaction scheme of Example C was followed, 20 using 2.0 g. of 3-amino-4-chloro-2-iminobenzothiazoline in ,~
30 ml. of tetrahydrofuran in the presence of 1.1 g. of triethylamine~ The starting compound was acylated with 1.5 ;
g. of chloroformic acid methyl ester, and the reaction time , was only about 2 hours. The product was identified as ; , 3-amino-4-chloro-2-methoxycarbonyliminobenzothiazoline, m.p.
222-23C., by nuclear magentic resonance and ultraviolet analysis, mass spectroscopy and elemental microanalysis.

. , ~'~
X-43~6 -10-' .; ' . ' "

~Q5~:~5'20 Theoretical Found C41.95~ 41.92 1~3.13 3.16 N16.37 16.10 I'he following examples illustrate the prep-aration of the compounds of formula (I).
Example 1 A 9.2 g. portion of 3-amino-2-methoxycarbonyl-imino-4-methylbenzothiazoline, produced by the process of Example C, was heated in a flask in a Woods metal bath at approximately 220C. for approximately 1-1/2 hours. The flask was then allowed to cool, and the product was re-crysta~lized from dimethylforlllamide to produc:e 5.9 g. of 2-hydroxy-5-methyl-s-triazolol5,1-bJbenzothia;~ole, ~II.p.
higher than 300C., the elemental microanalysis of which was as follows.
Theoretical Found C52.67% 52.62%
H3.44 3.59 N20.47 20.33 Example 2 A 4 g. portion of 3-amino-4~chloro-2-iminobenzo-thia~oline was slurried in 50 ml. of xylene. To the mixture was added 3.7 c~. of triethylorthoformate dissolved in about 10 ml. of xylene. The mixture was then heated very slowly to the reflux temperature. The ethanol which distilled from the mixture was collected in a Dean-Stark trap. After about 1 hour, the mixture was allowed to cool. The cooled reac-tion mixture was filtered, and the solids were washed with : . ,.. . :
:

1~9S2~

benzene. The yield was 2.8 g. of 5-chloro-s-triazolo-~5,1-b]be~zothiazole, m.p. 203-05C., which was identified by nuclear magnetic resonance analysis and elemental micro-analysis.
Theoretical Found C45.83% 45.9~ ;
H1.92 1.99 N20.04 19.94 Example 3 A 15 g. portion of 1-acetyl-2-(2-methylphenyl)-hydrazine was mixed with 75 ml. of benzene, and 16.4 g. of sodium thiocyanate was added. The reaction mixture was heated to 45C., and 16 g. of trifluoroacetic acid was added. The mixture was then heated to reflux temperature, and stirred at that temperature for 3-1/2 hours. Excess benzene was then decanted, and the thick residue was poured into water. An equal volume of ethyl acetate was added, and the solids were separated from the mixture by filtration and washed wlth ethyl acetate to yield 4-acetyl-3-(2-methyl-phenyl)thiosemicarbazide.
The above intermediate product was slurried in 70 ! ~ ml. of ethylene dichloride, and 5.3 g. of bromine dissolved in 30 ml. of ethylene dichloride was added dropwise with stirring. The mixture was heated to reflux temperature and stirred at that temperature for 1-1/2 hours. The mixture was then allowed to cool to room temperature and stirr~d overnlght. Then the reaction mixture was diluted with an equal volume of ethyl ether, and the white solids were separated by filtration and washed with additional ethyl .

..

s9s~

ether. The product was identified as 3-acetylamino-2-imino-4-methylbenzothiazoline, HBr salt, by infrared ~nd nuclear magnetic resonance analysis.
The above product was slurried in 100 ml. of water. The mixture was made neutral with NH40H, and the product was recovered by filtration. The product was 3-acetylamino-2-imino-4-methylbenzothiazolin~.
One g. of the above product was dissolved in 50 ml. of acetic acid, and the solution was stirred at reflux temperature for 28 hours. Dioxane was then added, and most of the acetic acid was removed as an azeotrope by distil-lation. The remaining reaction mixture was poured into a large amount of water, and the aqueous mixture was neutra-lized with potassium bicarbonate. The mixture was then repeatedly extracted with ethyl acetate, and the ethyl acetate layers were combined and evaporated under vacuum to leave an oil, which partially solidified on standing. The residue was triturated in a 4:1 mixture of ethyl ether:
chloroform, and the mixture was filtered. The filtrate was chromatographed on a silica gel column, eluting with a 2:1 mixture of benzene:ethyl acetate. The product-containing fractions were combined and evaporated under vacuum, to produce 2,5-dimethyl-s-triazolo[5,1-b]benzothiazole, m.p. 121-23C.
Example 4 A 2.2 g. portion of the intermediate product made in Example B was slurried in 15 ml. of polyphosphoric acid. The mixture was heatQd to about 110C. for about X-43~6 -13- -. . .
, ~QS95'~0 1-1/2 hours. The mixture was then allowed to cool to room temperature, and was diluted with a large amollnt of water. The aqueous mixture was neutralized with NH4OH
and filtered to separate the crude product. After re-crystallizing there was obtained 2,5-dimethyl-s-triazolo-[5,1-b~benzothiazole, m.p. 121-23C.
The synthetic methods of examples 1-4 are used, with appropriate variations which can be supplied by an ordinarily skilled organic chemist, to produce all of the compounds of formula (I), such as the following examples.
Example 5 ~` 5-methyl-s-triazolo[5,1-b]benzothiazole, m.p. 134-35C.
Example 6 -- : .
2,5-dimethyl-s-triazolo[5,1-b]benzothiazole, m.p. 121-23C.

Example 7 ,:
i, 5-fluoro-s-triazolo[5,1-b]benzothiazole, m.p. 165-67C.

`~ Example 8 5-fluoro-2-methyl-s-triazolo[5,1-b]benzothiazole, m.p.

162 64C.
.:"
Example 9 ~, . ~ .
~ , 5-methoxy-s-triazolo[5,1-b]benzothiazole, m.p. 142-43C.
., .
- Example 10 ..
7-methyl-s-triazolo[5,1-b]benzothiazole, m.p. 156-58C.

Example 11 2,7-dimethyl-s-triazolo[5,1-b]benzothiazole, m.p. 118-19C.

Example 12 5-chloro-2-methyl-s-triazolo[5,1-b]benzothiazole, m.p.

263-64C.
. ...
::.
?~, ~ , -:~
-~ X-4326 -14-... .
.....
,:~
.
~, . .
'~

: ' . . `' ' . ' ': : .
' -~0S952Q
~xample 13 5-chloro-2-hydroxy-s-triazolol5,1-b]benzothiazole, m.p.
340-41C. dec.
Example 14 5-methoxy-2-methyl-s-triazolo[5,1-b]benzothiazole, m.p.
146-47C.
Example 15 5-ethyl-s-triazololS,l-b]benzothiazole, m. p . 93-96 C .

Examp l e 16 5-ethyl-2-methyl-s-triazolo[5,1-b]benzothiazole, m.p.
g5-96C.
The compounds of formula (I) have been shown in a number of in vivo tests to reduc~ the adverse e~ects of foliar fungi. The fir~t ~roup of examples below illustrate the tests in which the compounds have been evaluated against ; fungi.
The compounds of formula (I) were formulated for testing by dissolving or suspending about 3.5 weight percent of each compound in 50:50 acetone:ethanol containing about 10 g./100 ml. of a nonionic surfactant. The solution was then dispersed in deionized water in a quantity such that the water dispersion containéd the various compound concen-trations indicated in the tables below. Concentrations were measured in parts per million by weight. The compound dispersions were applied to the test plants by spraying them with an air atomizer, using sufficient dispersion to wet the plants thoroughly. Compounds were formulated and applied differently in the bean rust tests, as shown below.

;

~059S20 Untreated, infected controls and untreated, normal controls were included in each test. The results lre reported on a 1-5 rating scale where l indicates severe disease and 5 indicates complete control of the disease. An empty space in the tables shows that the indicated compound was not tested at the indicated rate. In some cases, more than one test was performed against a given phytopathogen, and the results in such cases are reported as averages.
Compounds are identified by the example numbers used above.
The following specific test methods were used.
Test l _ helminthosporium leaf spot of wheat Healthy wheat seed was planted in sterile green-; house soil. When the seedlings were 4-5 inches tall, they were sprayed with test compound dispersions. The day after treatment, the plants were inoculated with a spore sus-pension of Helminthosporium sativum which had been grown on potato dextrose agar. The plants were placed in a moist growth chamber for two days to start disease growth, and were then transferred to the greenhouse. About a week after treatment~ the plants were observed and the results were ! recorded.
Test 2 late blight of tomato Four-week-old tomato seedlings were sprayed with aqueous dispersions containing test compounds. The fo~-lowing day, the foliage was inoculated with an a~ueous suspension of propagules of Phytophthora infestans. The inoculum had been reared on infected wheat seed. The plants were held and observed as described above.

,. ~ , , . ~ .

~595~() 'I`est 3 ~_wdery mildew of bean .
The host plants were 10-day-old bean seedlings.
After aqueous dispersions containing test compounds had been sprayed on the foliage of the beans and allowed to dry, the plants were placed in the greenhouse and inoculated by storing them under other bean plants which were heavily infected with powdery mildew (Erys phe poly~ni). After about 10 days, the plants were observed and the results recorded as usual.
Test 4 _ anthracnose of cucumber ' Aqueous dispersions containing test compounds were applied to healthy cucumber seedlings grown in sterilized , greenhouse soil. The following day, the plants were in-, oculated with Colletotrichum lagenarium conidia as an aqueous suspension. The fungus had been grown on potato , .;
, dextrose agar in petri dishes. The plants were held in a moist chamber for two days and transferred to the green-, 20 house, and the disease was observed and rated approximately ; ' 12 days after application of the test compounds.
, Test 5 rice blast of rice . _ _ The test compound dispersions were applied to , healthy rice seedlir,~gs growing thickly in plastic pots. The plants were inoculated on the next day with Piricularia oryzae (grown on rice polish agar) and the plants were held in a moist char,nber for two days. The plants were then held ,-' in the greenhouse for 5-7 days and observed.
~ .

1.~5~3S20 Test 6 bean rust of bean ~ into bean seedlings were raised in plastic pots in the greenhouse. One week after the seeds were planted, 10 ml. of a 400 ppm. aqueous dispersion of the compound to be tested was added to the soil in which each treated plant was growing, providing a rate of 12.3 kg./ha. The following day, the plants were inoculated with spores of bean rust (Uromyces phaseoli var. typica) which were grown on pinto bean plants and applied to the test plants as an aqueous dispersion. The plants were held for two days in a moist chamber, transferred to the greenhouse, and observed about 10 days after inoculation with the phytopathogen.
Test 7 ; cercospora leaf spot of sugar beet Sugar beet seedlings were transplanted into square plastic pots and allowed to grow for three weeks. Aqueous dispersions containing the compounds to be tested were sprayed on the leaf surfaces. After the dispersions dried, but within 24 hours, the plants were inoculated with a conidial suspension of Cercospora beticola which had been grown on sugar beet leaf decoction agar. After the plants were held in a moist chamber for two days, they were trans-ferred to the greenhouse and observed 2-3 weeks later.
Test 8 .
botrytis of ~rape Sound grape berries were sterilized by immersion in diluted sodium hypochlorite and thoroughly rinsed. The berries were placed on wire screen shelves in compartmented " .

s9szo Pyrex plantes. The berries were then flamed and sprayed with test chemical dispersions. The following da~, the berries were inoculated hy spraying 5 ml. of a conidial sus-pension of Botrytis cinerea over each plate containing 12 berries. The inoculum had been grown on frozen lima bean agar. A small amount of water was added to each plate and a cover was sealed over each plate. After 48 hours at 25C., the berries were observed and disease ratings recorded.
Test 9 .
apple scab of apple Apple seedlings at the 4-6 leaf stage were sprayed with aqueous dispersions of the test compounds. The fol-lowing day, the plants were sprayed with a suspension of fresh conidia of Venturia inae~ualis obtained from infected apple seedlings kept as a source of inoculum. The plants ; were held for two days in a 20C. moist chamber to start disease growth and were then transferred to the greenhouse.
; About two weeks after application of the compounds, the plants were observed and the results were recorded.
Test 10 downy mildew of grape Young expanding grape leaves were detached from healthy vines on the day of the test. Leaves were placed individually in plastic petri dishes, bottom side up, on top of an expanded plastic mat. Water was added to each petri dish, and the petiole of each leaf was wrapped with a water-soaked wad of cotton. Each leaf was sprayed with an aqueous dispersion of the compound to be tested.

.

~s~s~
After the test compound dispersions had dried, the leaves were inoculated by atomizing a conidial sus~)ension of Plasmopara viticola (grown on infected leaf tissue) evenly over the leaf surface. The plates were then covered and were stored in a growth room at about 18C. and 100~ rela-tive humidity where they were exposed to 8 hours a day of artificial light. After about a week of storage, all the .
leaves were observed and the signs of disease were evalu- ~
ated. ;
The following table reports results of testing ~ typical compounds of formula (I) by the above methods.

:

i i , ~' '" ' , ' ' .

.

, . . .

' .

,., . . . ~ . ..
.. . . . .

~o~9~z~

~?~O(~SO~

Mapl l w l ~

~; , .
qe~s 3Idd~

~unl~ods -ou~u~ aH ~
la I

a~e~
, ~sn~ *
uea~
~1 .

~sel~ u~ r a ~ i3sou~ u~

, :
~: : ~aPlFW r~
aP~o O o o ~ ~ o o In ~D
o o o t~ o o ~

~3 X Z ~
~', ;............. , ~ '` ~ :

~(~595;20 .
e~odsoala;~ ¦
., ~PI IW ,~ ,., ~u~oa .: ~ ~r ~ qe~s ¦
aldd~ I

umF~ods I
_o~uFull aH
. , ~
F I
; . a~ e~
: ~.
~ ~ ~sn~ ¦
: :~ o ura~ t ,-, S~O~ I ~
.~ O
,4 ~SeT~ I
,; , E~ a::~F~ ~ u~
~ _I _I ~r ~ N ~ ~ ~1 ~
asou~e~u~

:: ` M~3PT 1~ , pMO'a ~ ~ , .

. ! ~

Q O O ~1 0 0 ~ O O ~ O
O

X Z

~59~20 e~odso~a~

Mapl lW I
i~UM

qeo aldd~

umF~ods _ou,~u~ 3H ¦

~FI~I

:~sn~
uea~ *

SF~ O~ ¦

E~ ~ S e aSou:~e~U~ ¦ u u~

.` M~pl F~ u~
apM
.,,' ,¢ p~; ~ o o u~ ~D o O O

~a ~:: a o Q~
- ~ ~ æ
~' ~ ,, ~Q595'2~

Tvpical compounds of formula ~I) hav~ also been tested in a syst~m which evaluated the compoun~s' -Ihility to control rice blast systemically. The compounds were applied either to the soil in which rice plants were grown, or to rice seed, and the extent to which the compound controlled artificially inoculated rice blast was observed.
Test 11 seed soak test -Test compound dispersions were prepared as described above, except that ethanol was used in place of acetone:ethanol, and the final aqueous dispersions always contained 0.5 ~ercent of ethanol regardless of the concen-tration of the active compound. Compound concentrations of 250, 500 and 1000 ppm. were used.
Rice seed was treated by shaking 20 ml. of Nato rice and 20 ml. of a compound dispersion for 48 hours in a stoppered flask. After the shaking period, the rice seed was drained and thoroughly rinsed with tap water. The seed was planted, and the seedlings were inoculated with P.
_~y~ae by spraying the foliage with a P. oryzae culture.
The inoculated plants were held for 2 days in a moist chamber and observed.
Test 12 soil surface-applied test The compounds were formulated as described at the beginning of the test method discussion, and were applied to the soil surface of pots in which 10-cm. xice seedlings were growing. The volume of test compound dispersions was always 75 ml., and rates from 28 kg./ha. to 1.4 kg./ha. were used.

:i . . . .
, ' , ' ~

~)S~5'ZO

Two days after application of the compounds, the plants were inoculated and held for observation as described in the test method immediately above.
Test 13 soil-incorporated test Sterile greenhouse soil was treated with the proper amounts of test compounds, dis~olved in ethanol, to provide treatment rates from 1.4 to 28 kg./ha. The com-pounds were thoroughly mixed with the soil in a rotating drum mixer. Rice seed was planted in the treated soil, and the emerged rice seedlings were inoculated and observed as described above.
Seed Soak Treatment Compound of ~pln.
I~xamplel~atc ~iscasc No. ppm. Rating , 2 1000 4.3 500 4.3 :
1000 3.3 250 2.7 6 1000 1.3 500 1.3 250 1.3 500 1.3 ', ~595~0 Seed Soak Treatment Compound of A~ln.
ExampleRate Disease No. ~pm. Ratin~

500 1.3 250 1.7 ; 15 1000 2.3 . 10 250 2.3 Soil Surface Treatment : Compound of Appln.
Example Rate Disease . No. pp-m.- Rating . .~ .
~ . 2 5.6 4 r 2.8 3.7

4 3 28 4~3 :
~;~ 1 4 4 7 4~3 .. 1 , .
: ~ 2 0 5 ~ 6 4 ~ 3 , - 2.8 3.7 1~4 2 .
. .
. . .
.

~.l . .
: ~ , .
'''~
', :i .~ .

.~ .

S'ZO

Soil Surface Treatment .
Compound of A~E~ln.
Ex(lmple Rat~ Dis~as~
No. ~n. Ratir~
_ 14 1.3 7 1.3

5.6 5 ~: 2-8 4.3 - 1.4 3 7 ::
7 2 8 5 ~ .
14 5 :

. 9 28 1.3 :
14 1.7 7 1.3 28 2 . 7 ~ . .
~ ' ;'''. ' i' .. . .

::
.' ~ ~-.

~ X-4326 -27-.

., ~ ..... . ... . . . .

1.C~55~5ZO

So _ Incorç~ration Treatment Compound of Appln.
Example Rate Disease No. _ ~./ha. Ratin~_ 2 5.6 4 2.8 1.4 5.6 3 2.8 1.7 1.4 1.3 7 5.6 4.3 2.8 3.7 1.4 2 9 28 1.3 . 7 1.3 7 1.3 .. .. ..

.. . . . . .
' ~- . . " . . ~ . ' , :

~(~59S20 The method of reducing the adverse effects of plan~ foliage-attacking ~un(3i is carried out accor(~ing to the methods and principles which are well knowl~ in agri-cultural chemistry. Detai le~ discussion ~f the m~thod will be provided to assure that agricultural chemists can gain the best advantage from the use of the compounds of formula (I) described herein.
The present method of reducing the adverse effects of plant foliage-attacking fungi comprises contacting the fungi with an effective fungus-inhibiting amount of one of the new compounds of formula (I). The preferred use of the method is in reducing the adverse effects of _. oryzae on rice. 'l'he compounds with which the l!lethod is preferably carried out are 5-chloro-s-triazolo[5,1-bJbenzothiazole, 5-methyl-s-triazololS,l-nJbenzothiazole, 5-fluoro-s-tria-zolo[5,1-b]benzothiazole, and 2,5-dimethyl-s-triazolo-[5,1-b]benzothiazole.
Practice of the mPthod need not necessarily kill ; ~ all of the contacted fungi in order to confer its benefit on ! 20 the treated plants. Proper use of the method kills part of the fungi, and inhibits another part of the fungi by in-juring, or slowing growth of, the organisms. As the data above show, application of a sufficient amount of a compound to inhibit the fungi reduces the adverse effects of the disease, whether all of the fungus population is killed by the compound or not.
As is usual in the plant protection art, best results are obtained by applying the compound several times .

1(~5~5ZO

during the growing season at intervals of from 1 to a few weeks, depending on the weather and the severity ~ the disease. The methods of formulating the compounds and pre-yaring dispersions of the formulations, and the methods of applying dispersions of the compounds to the plants to be protected, are entirely conventional in the plant protection art. Some explanation of the methods of application will be given merely to assure that those skilled in the art can carry out the invention without undue experimentation.
The compounds of formula (I) can be used for the control of foliage-attacking fungi by either applying the compound to the foliage of the plants, where they directly contact the fungi, or by applying the compounds to the soil, where they are absorbed by the roots of the plants and carried through the plant's tissues to the foliage where they contact the fungi and reduce their adverse effects.
Both methods of application are regularly in use in the plant protection art.
It is usual in describing foliar applications of plant protectants to measure the application rate by the concentration of the dispersion in which it is applied. The application rate is measured in this way because it is customary to apply a sufficient amount of the dispersion to , cover the foliage with a thin film. The amount of dis-persion applied is thus dependent on the foliar area of the plant, and the quantity of plant protecting compound is , dependent upon its concentration in the dispersion.
Compound concentration in the range of from about 25 to about 1500 parts of compound per million parts by .1 -.

.
:- .... . . :

weight o~ the dispersion are used in the practice of the antifunyal method of this il~vention, when the funq are contact~d by applying the compound to the foliage. Of course, from time to time, higher or lower concentrations will be useful, depending on the severity of the infection and the characteristics of the specific compound in use.
The named range, however, encloses the usual optimum con-centrations of the compounds.
When the method is carried out by applying the compound to the soil in which the plants grow, it is most meaningful to describe the application rate in terms of the amount of compound applied per unit area of soil. Compound application rates in the range of from about 1 to about 50 kg./ha. are used in the practice of this invention to reduce the adverse effects of foliage-attacking fungi. As pre-viously described, application rates higher and lower than the named-range will at times be useful.
The dispersions in which the compounds are appliecd , to foliage are most often aqueous suspensions or emulsions prepared from concentrated formulations of the compounds.
Such water-suspendible or emulsifiable formulations are either solids usually known as wettable powders or liguids usually known as emulsifiable concentrates. Wettable powders comprise an intimate mixture of the active compound, an inert carried and surfactants. The concentration of the active compound is usually from about 10 percent to about 90 percent by weight. The inert carrier is usually chosen from among the attapulgite clays, the montmorillonite clays, the ~(~5~S'~O

diatomaceous earths, or the purified silicates. Effective surfactants, comprising from about 0.5 percent to ~bou~ 10 percent of the wettable powder, are found among the sul-fonated lignins, the condensed naphthalenesulfonates, the naphthalenesulfonates, the alkylbenzenesulfonates, the alkyl sulfates, and nonionic surfactants such as ethylene oxide ; adducts of alkyl phenol.
Typical emulsifiable concentrates of the compounds comprise a convenient concentration of the compound, such as from about 100 to about 500 g. per liter of liquid, dis-solved in an inert carrier which is a mixtùre of water-immiscible organic solvent and emulsifiers. Useful organic solvents include the aromatics, especially the xylenes, and the petroleum fractions, especially the high-boiling naphthalenic and olefinic portions of petroleum such as heavy aromatic naphtha. Other organic solvents may also be used, such as the terpenic solvents including rosin deriva-tives, and complex alcohols such as 2-ethoxyethanol. Suit-able emulsifiers for emulsifiable concentrates are chosen from the same types of surfactants used for wettable powders.
Adjuvants are frequently used to improve the ability of the aqueous dispersion to coat and adhere to - foliage. Such adjuvants as gums, emulsified polybutenes, cationic surfactants and lignin derivatives can often increase the potency of the method in a specific use.
Less frequently, the compounds are applied in the form of dusts. Agricultural chemical dusts typically com-prise the compound in a finely powdered form, dispersed in a ,, .

1059S~0 powdered inert carrier. Most often, the carrier is a powdered clay, such as pyrophyllite, bentonite, a volcani~
deposit, or montmorillonite. Dusts are usually prepared to contain concentrations of the compound at the highest part of the concentration range, such as 1500 ppm., and may contain even more active ingredient.
Dispersions of the compounds are applied to foliage in the usual manners. Low-pressure sprayers, high-pressure sprayers and low-volume air blast equipment are all effective for the application of water-dispersed compounds of formula (I). Dust dispersions are readily applied by means of the usual equipment which blows the dust into intimate contact with the foliage.
The same types of dispersions used for application to plant foliage can also be applied to the soil. In addition, the compounds can economically and conveniently be applied to the soil in the form of granular formulations.
'~ Such formulations, well known to the agricultural chemical art, are prepared by dispersing the compound on an inert carrier of controlled granular character. Most often, the carrier is a coarsely ground clay, such as attapulgite or kaolin clay, having a particle size in the range of from 0.5 ; to 3 mm. Such granular formulations are easily applied to the soil with applicators which are specially designed to apply accurately çontrolled amounts of the granular products to the soil.

, . . .. . .

Claims (5)

The embodiments of the invention in which an exclu-sive property or privilege is claimed are defined as follows:

1. A compound of the general formula (I) wherein R is hydrogen, hydroxy or methyl; and' R1 is methyl, ethyl, chloro, fluoro, or methoxy; and provided that the methoxy R1 group occupies only the 5-position.

2. A compound according to Claim 1 wherein R
is hydrogen and R1 is methyl, chloro or fluoro.

3. Any one of the following compounds:
2-hydroxy-5-methyl-s-triazolo[5,1-b]benzothiazole 5-chloro-s-triazolo[5,1-b]benzothiazole 5-fluoro-2-methyl-s-triazolo[5,1-b]benzothiazole 5-methyl-s-triazolo[5,1-b]benzothiazole 2,5-dimethyl-s-triazolo[5,1-b]benzothiazole 5-fluoro-s-triazolo[5,1-b]benzothiazole 5-methoxy-s-triazolo[5,1-b]benzothiazole 7-methyl-s-triazolo[5,1-b]benzothiazole 2,7-dimethyl-s-triazolo[5,1-b]benzothiazole 5-chloro-2-methyl-s-triazolo[5,1-b]benzothiazole 5-chloro-2-hydroxy-s-triazolo[5,1-b]benzothiazole 5-methoxy-2-methyl-s-triazolo[5,1-b]benzothiazole 5-ethyl-s-triazolo[5,1-b]benzothiazole 5-ethyl-2-methyl-s-triazolo[5,1-b]benzothiazole.

4. A process for the preparation of a compound of the general formula I
wherein R is hydrogen , hydroxy, or methyl; and R1 is methyl, ethyl, chloro, fluoro, or methoxy; and provided that the methoxy R1 occupies only the 5-position, which comprises reacting a compound of the general formula II
wherein R1 is defined as before, and R2 is NH or , wherein R3 is methyl, methoxy, or hydrogen, or its isomer (enol form) when R2 is , with a cyclizing agent.

5. A method of reducing the adverse effects of foliage-attacking fungi which comprises contacting the fungi with an effective fungus-inhibiting amount of a compound of claim 1, 2 or 3.