Thio compounds having fungicidal activity

The invention relates to new thio compounds of the general formula ##STR1## wherein R is an alkyl group substituted or not substituted with halogen and having 1-12 carbon atoms, an alkenyl or alkynyl group having 2-4 carbon atoms, an alkadienyl group having 3 or 4 carbon atoms or a substituted or unsubstituted phenyl or phenyl(C.sub.1 -C.sub.4)alkyl group; PA0 R.sub.1 is a cyano group, a formyl group, an alkylcarbonyl or alkoxycarbonyl group substituted or unsubstituted with halogen and having 2-5 carbon atoms, a substituted or unsubstituted benzoyl group, or an alkylsulphonyl group having 1-4 carbon atoms; PA0 R.sub.2 is a hydrogen atom, a halogen atom, an amino group unsubstituted or substituted with one or two groups selected from C.sub.1 -C.sub.4 alkyl and C.sub.2 -C.sub.5 alkylcarbonyl, an amino group forming part of a heterocyclic ring which may comprise 1 or 2 additional heteroatoms selected from N, O and S, an alkyl or alkoxy group having 1-4 carbon atoms and optionally substituted with C.sub.2 -C.sub.5 alkylcarbonyl, or a substituted or unsubstituted phenyl, phenoxy or phenylthio group; or wherein PA0 R.sub.1 and R.sub.2, together with the vinylene group to which they are bound, constitute a substituted or unsubstituted phenyl group; PA0 X is a cyano group or a formyl group; PA0 n is 1 or 2; PA0 Y is an alkylthio group having 1-4 carbon atoms; and PA0 Z is a hydrogen atom, a halogen atom, a nitro group, or an alkyl or alkoxy group having 1-4 carbon atoms and optionally substituted with halogen; or wherein Y and Z together constitute a sulphur atom; with the proviso that, when Y and Z do not together constitute a sulphur atom, R.sub.1 and R.sub.2, together with the vinylene group to which they are bound, constitute a substituted or unsubstituted phenyl group. The new compounds show a fungicidal and/or bactericidal activity and may be used in particular against plantpathogenic seed fungi and soil fungi and/or bacteria.

The inventions will now be described in greater detail with reference to 
the following specific examples. 
EXAMPLE I 
Preparation of 2-methylsulphinyl-3-cyano-5-acetylthiophene (1). 
5.0 g of 83% m-chloroperbenzoic acid are gradually added while stirring at 
a temperature of 0.degree.-5.degree. C. in 45 minutes to a solution of 5.0 
g of 2-methylthio-3-cyano-5-acetylthiophene in 500 ml of methylene 
chloride. After stirring for another 30 minutes at 5.degree. C., a 
saturated solution of sodium bicarbonate in approximately 50 ml of water 
is added; the reaction mixture is then stirred for 60 minutes. The organic 
layer is separated, washed with water and dried. After distilling off the 
solvent, the desired product is obtained in a yield of 4.6 g; 
melting-point 150.degree. C. 
In a corresponding manner, in which, optionally, p-nitroperbenzoic acid is 
used as an oxidant and chloroform as a solvent, the following compounds 
are prepared: 
______________________________________ 
Melt. point .degree.C. 
Comp. (phys. char.) 
______________________________________ 
(2) 153 
(3) 148 
(4) 145 
(5) 94 
(6) 186-188 
(7) 130 
(8) 80 
(9) 109 
(10) 166 
(11) 192-195 
(12) 130 
(13) 100 
(14) 98 
(15) syrup; R.sub.f (CH.sub.2 Cl.sub.2) = 0.25 
(17) 130 
(19) syrup; R.sub.f (CH.sub.2 Cl.sub.2) = 0.30 
(20) 115-118 
(23) 74 
(24) 94 (decomp) 
(25) 120 
(26) 171-173 
(27) 156-158 
(28) 112-115 
(29) 167-169 
(30) 127,5-133,5 
(31) 91-97 
(32) 90-93 
(33) 104-105,5 
(34) 58 
(35) 169-171 
(36) oil: R.sub.f (CH.sub.2 Cl.sub.2) = 0.20 
(37) 77-79 
(38) 119 
(39) 70-71 
(40) 72-74 
(41) 70 
(42) 123-127 
(43) 78-79 
(44) 80-81 
(46) 143-146 
(47) 103-106 
(48) 170-172 
(49) 137-139 
(50) 82-87 
(51) 124-128 
(52) 136.5-138 
(53) oil; R.sub.f [(C.sub.2 H.sub.5).sub.2 O] = 0.30 
(54) syrup; R.sub.f (CH.sub.2 Cl.sub.2) = 0.22 
(55) 83 
(56) 76-78 
(57) 155-157 
(58) 143-145 
(59) 120 
(60) 146-151 
(61) 114-116 
(62) 46-48 
(63) 93-95 
(64) 86-88 
(65) 164-167 
(66) 174-177 
(67) 124-127 
(68) 127-128 
(69) 125-128 
(70) 140-142 
(71) 124-126 
(72) 109-111 
(73) 82-86 
(74) 79-84 
(75) 69-72 
(76) 151 (decomp) 
(77) 172-174 
(78) 149-151 
(79) 113-115 
(80) oil; R.sub.f (CH.sub.2 Cl.sub.2) = 0.18 
(81) oil; R.sub.f (CH.sub.2 Cl.sub.2) = 0.15 
(82) 132-135 
(83) 90-92 
(85) 99-101 
(86) 84-86 
(87) 117-119 
(88) 90-92 
(90) oil; R.sub.f (CH.sub.2 Cl.sub.2) = 0.14 
(91) 68-73 
(92) 110 
(93) 84-87 
(94) 94-96 
______________________________________ 
EXAMPLE II 
Preparation of 2-ethylsulphonyl 3,5-dicyanothiophene (16). 
2 ml of 35% hydrogen peroxide are added to a solution of 1.62 g of 
2-ethylthio-3,5-dicyanothiophene in 50 ml of aetic acid. After heating at 
approximately 100.degree. C. for approximately 1 hour, another ml of 35% 
hydrogen peroxide is added, succeeded by heating for another hour at 
approximately 100.degree. C. Upon cooling the substance crystallises out 
and can be sucked off. After washing with ethanol the desired compound is 
obtained in a yield of 1.49 g; melting-point 121.degree.-124.degree. C. 
The following compounds are prepared in a corresponding manner: 
______________________________________ 
Compound Melting-point .degree.C. 
______________________________________ 
(18) 138-140 
(21) 115-117 
(22) 140-143 
(45) 189-191 
(84) 216-218 
(89) 119-121 
______________________________________ 
EXAMPLE III 
Preparation of 2-methylthio-3,5-dicyano-4-aminothiophene. 
A concentrated solution of 50 g of KOH in approximately 30 ml of water is 
slowly added dropwise to a solution of 26.5 g of malonic acid dinitrile in 
approximately 250 ml of dimethyl formamide to which 45 ml of carbon 
disulphide have been added. During the addition the mixture is stirred and 
kept at a temperature of 0.degree.-10.degree. C. by cooling. After 10 
minutes, 60.0 g of methyl iodide are slowly added dropwise while stirring 
and cooling and then, after 30 minutes, 30.5 g of chloroacetonitrile. The 
cooling bath is removed and 4.0 g of powdered KOH are added, the 
temperature of the reaction mixture rising to approximately 42.degree. C. 
After stirring for another hour at 30.degree.-35.degree..degree. C., 600 
ml of water and 100 ml of diethyl ether are added, after which the formed 
precipitate is sucked off, washed successively with water, isopropyl 
alcohol and diethyl ether, and dried. The desired product is obtained in a 
yield of 54.5 g and sublimates at 260.degree. C. 
The following compounds are prepared in a corresponding manner: 
2-ethylthio-3-cyano-4-amino-5-acetylthiophene, used for the preparation of 
compound (10) according to Example I. 
2-methylthio-3-cyano-4-amino-5-ethoxycarbonylthiophene, used for the 
preparation of compound (29) according to Example I; 
2-n-hexylthio-3,5-dicyano-4-aminothiophene, used for the preparation of 
compound (38) according to Example I; 
2-ethylthio-3,5-dicyano-4-aminothiophene, used for the preparation of 
compound (46) according to Example I; 
2-methylthio-3-cyano-4-amino-5-formylthiophene, used for the preparation of 
compound (48) according to Example I; 
2-ethylthio-3-cyano-4-amino-5-formylthiophene, used for the preparation of 
compound (49) according to Example I; 
2--n-propylthio-3-cyano-4-amino-5-acetylthiophene, used for the preparation 
of compound (57) according to Example I; 
2-n-butylthio-3-cyano-4-amino-5-acetylthiophene, used for the preparation 
of compound (58) according to Example I; 
2-ethylthio-3-cyano-4-amino-5-benzoylthiophene, used for the preparation of 
compound (65) according to Example I; 
2-ethylthio-3-cyano-4-amino-5-(4-chlorobenzoyl)thiophene, used for the 
preparation of compound (66) according to Example I; 
2-n-propylthio-3-cyano-4-amino-5-benzoylthiophene, used for the preparation 
of compound (67) according to Example I; 
2-n-butylthio-3-cyano-4-amino-5-benzoylthiophene, used for the preparation 
of compound (88) according to Example I; 
and furthermore: 
2-methylthio-3-cyano-4-amino-5-acetylthiophene; 
2-ethylthio-3,5-dicyano-4-aminothiophene; 
2-ethylthio-3-cyano-4-amino-5-formylthiophene; 
2-n-propylthio-3,5-dicyano-4-aminothiophene; 
2-methylthio-3-cyano-4-amino-5-formylthiophene; 
2-methylthio-3-cyano-4-amino-5-benzoylthiophene; 
2-n-octylthio-3,5-dicyano-4-aminothiophene; 
2-ethylthio-3-cyano-4-amino-5-ethoxycarbonylthiophene; 
2-methylthio-3-cyano-4-amino-5-(4-chlorobenzoyl)thiophene; 
2-n-butylthio-3,5-dicyano-4-aminothiophene; 
2-n-propylthio-3-cyano-4-amino-5-(4-chlorobenzoyl)thiophene; and 
2-benzylthio-3,5-dicyano-4-aminothiophene. 
EXAMPLE IV 
(a) The thiophenes unsubstituted in the 4-position and used for the 
preparation of the compounds (1), (4), (8), (9), (16), (21), (28), (30), 
(40), (44), (47), (51), (52), (64), (73), (80), (81) and (90), mentioned 
in Examples I and II, are prepared as follows from the corresponding 
4-aminothiophenes obtained according to Example III: 
Preparation of 2-methylthio-3,5-dicyanothiophene. 
20.0 g of 2-methylthio-3,5-dicyano-4-aminothiophene obtained according to 
Example III are added portion-wise to a solution of 20.0 g of 
isoamylnitrite in 300 ml of dimethyl formamide at 62.degree. C. while 
stirring. At a temperature of 65.degree.-70.degree. C. stirring is 
continued for another 30 minutes and the reaction mixture is then 
evaporated to approximately 100 ml. After the addition of 400 ml of water, 
the formed precipitate is sucked off, washed successively with water, 
isopropanol and petroleum ether, taken up in approximately 300 ml of 
methylene chloride and dried. The solution is filtered over silica gel and 
decolorized with charcoal. After the addition of isopropanol and 
evaporating methylene chloride, the crystalline product is sucked off, 
washed successively with isopropanol and petroleum ether, and dried. The 
desired compound is obtained in a yield of 14.0; melting-point 117.degree. 
C. 
(b) The 4-halothiophenes used for the preparation of the compounds (2), 
(3), (5), (7), (18), (22), (31), (33), (34), (36), (37), (39), (42), (43), 
(50), (61), (72), (78), (79), (86), (89) and (92), mentioned in Examples I 
and II, are prepared as follows from the corresponding 4-aminothiophenes 
obtained according to Example III. 
Preparation of 2-ethylthio-3,5-dicyano-4-chlorothiophene. 
Cupric chloride (CuCl.sub.2.2H.sub.2 O) in an amount of 100 g is dissolved 
in 300 ml of conc. hydrochloric acid. After addition of 2 l of 
acetonitrile, simultaneously a conc. solution of 60 g of sodium nitrite in 
water and 121.2 g of 2-ethylthio-3,5-dicyano-4-aminothiophene, obtained 
according to Example III, in portions are added while cooling at 
-5.degree. C. After stirring for an hour without external cooling the 
formed precipitate is sucked off and washed with acetonitrile. After 
evaporating the filtrate the residue is dissolved in methylene chloride 
and washed with water, dried, filtered and evaporated. The desired 
2-ethylthio-3 5-dicyano-4-chlorothiophene can be purified by dissolving in 
methylene chloride and chromatographing over silica. The product can be 
recrystallized by evaporating methylene chloride and adding diisopropyl 
ether. Yield 52.66 g; melting point 93.degree.-96.degree. C. 
Alternatively the 4-halothiophenes can be prepared as follows: 
Preparation of 2-n-butylthio-3-cyano-4-chloro-5-benzoylthiophene. 
Isoamyl nitrite in an amount of 15 ml is added to a mixture of 10.1 g of 
anhydrous CuCl.sub.2 in 100 ml of dry acetonitrile, kept at a temperature 
of 65.degree.-70.degree.. While stirring a solution of 15.8 g 
2-n-butylthio-3-cyano-4-amino-5-benzoylthiophene, obtained according to 
Example III, in 200 ml of dry acetonitrile, is added while maintaining the 
reaction temperature at ca. 65.degree. C. After stirring for half an hour 
at 65.degree.-70.degree. C. and cooling down to room temperature the 
reaction mixture is evaporated. The residue is dissolved in methylene 
chloride, after which 6N hydrochloric acid is added. The methylene 
chloride layer is separated, washed with 6N hydrochloric acid. dried, 
filtered and after suppletion of isopropanol, partially evaporated The 
desired 2-n-butylthio-3-cyano-4-chloro-5-benzoylthiophene crystallizes out 
and is sucked off and dried; yield 11.85 g; melting point 
78.degree.-80.degree. C. 
(c) 2-Ethylthio-3-cyano-4-N-methylamino-5-acetylthiophene used for the 
preparation of compound (17) mentioned in Example I is prepared as follows 
from the corresponding 4-aminothiophene obtained according to Example III: 
1.2 g of 55% sodium hydride are added portion-wise, while stirring, to a 
solution of 5.4 g of 2-ethylthio-3-cyano-4-amino-5-acetylthiophene in 100 
ml of dimethyl sulphoxide. The mixture is stirred for 45 minutes, after 
which 2.5 ml of dimethyl sulphate are slowly added. After stirring for 
another hour, the reaction mixture is poured into 400 ml of water. The 
formed precipitate is filtered off and washed successively with water, 
petroleum ether, little isopropanol and again petroleum ether. After 
recrystallisation from isopropanol, 
2-ethylthio-3-cyano-4-N-merhylamino-5-acetylthiophene is obtained in a 
yield of 2.73 g. 
(d) 2--Ethylthio-3,5-dicyano-4-(N-acetyl-N-methylamino)thiophene, used for 
the preparation of compound (54) mentioned in Example I, is prepared as 
follows from the corresponding 4-aminothiophene obtained according to 
Example III: 
To a suspension of 21 g of 2-ethylthio-3,5-dicyano-4-aminothiophene, 3 g of 
4-(N,N-dimethylamino)pyridine and 20 ml of triethylamine in 300 ml of 
acetonitrile, stirred at 50.degree. C., is added dropwise 18 g of acetic 
acid anhydride. After evaporation and taking up the residue in 
diethylether, containing 5% acetic acid, the precipitate is sucked off, 
washed successively with water, isopropanol, diethylether, toluene and 
diethylether again, and dried. The 4-N-acetylamino compound is obtained in 
a quantity of 16 g. To a mixture of 16 g of the last-mentioned compound 
and 12 g of K.sub.2 CO.sub.3 in 300 ml of acetonitrile is added 20 g of 
methyl iodide. The reaction mixture is stirred and refluxed for 5 hours, 
during which period 3 portions of approx. 12 g of methyl iodide are added. 
The liquid is decanted and the solid is washed with acetonitrile and 
methylene chloride successively. The total filtrate is evaporated to 
dryness and taken up into methylene chloride. After the addition of 
isopropanol, decolorizing with charcoal and evaporating methylene 
chloride, 2-ethylthio-3,5-dicyano-4-(N-acetyl-N-methylamino)thiophene is 
obtained in a yield of 9 g; melting point 68.degree. C. 
EXAMPLE V 
2-Methylthio-3,5-diformylthiophene, used for the preparation of compound 
(70) mentioned in Example I, is prepared as follows: 
To a suspension of 7.20 g of 2-methylthio-3,5-dicyanothiophene, obtained 
according to Example IV (a), in 120 ml of dry toluene is added, while 
stirring and under a nitrogen blanket, 75 ml of a 20% solution of 
diisobutyl aluminumhydride in toluene. The reaction mixture is stirred for 
two hours, after which 12 ml of methanol is added under cooling in ice. 
The reaction mixture is stirred in ice plus conc. sulphuric acid till a 
clear solution. The toluene phase is separated and the water phase washed 
twice with toluene. The combined organic phase is washed with water, 
dried, filtered and evaporated. The residue is recrystallized from ethanol 
yielding 2-methylthio-3,5-diformylthiophene in a quantity of 3.0 g; 
melting point 135.degree.-137.degree. C. 
In a corresponding way 2-ethylthio-3,5-diformyl-4-chlorothiophene, used for 
the preparation of compound (83) mentioned in Example I, is prepared from 
2-ethylthio-3,5-dicyano-4-chlorothiophene, obtained according to Example 
IV (b). 
EXAMPLE VI 
(a) Preparation of 2-methylthio-3,5-dicyano-4-hydroxythiophene. 
A cold, highly concentrated solution of 25 g of KOH in approximately 15 ml 
of water is slowly added dropwise to a solution of 20.0 g of cyanoacetic 
acid methyl ester and 18.0 g of carbon disulphide in approximately 300 ml 
of dimethyl formamide while stirring and cooling to below approximately 
0.degree. C. After stirring for another 20 minutes, a solution of 15.5 g 
of chloroacetonitrile in 10 ml of acetonitrile is added dropwise to the 
reaction mixture at -5.degree. C. to 0.degree. C. After stirring for 
another 30 minutes, a highly concentrated solution of 13 g of KOH in water 
is added and stirred for 30 minutes at 40.degree. C. Then 29 g of methyl 
iodide are added dropwise and, after 30 minutes, 25 ml of concentrated 
hydrochloric acid. After concentration of the reaction mixture under 
reduced pressure to approximately 300 ml, approximately 600 ml of water 
are added. The resulting precipitate is sucked off, washed successively 
with water, little isopropanol and di-isopropyl ether, and dried. The 
desired product is obtained in a yield of 19.0 g; the substance decomposes 
above 200.degree. C. 
The following compounds are prepared in a corresponding manner: 
2-ethylthio-3,5-dicyano-4-hydroxythiophene, 
2-ethylthio-3-cyano-4-hydroxy-5-acetylthiophene, 
2-propargylthio-3,5-dicyano-4-hydroxythiophene, 
2-methylthio-3-cyano-4-hydroxy-5-acetylthiophene. 
2-n-butylthio-3,5-dicyano-4-hydroxythiophene, 
2-n-propylthio-3,5-dicyano-4-hydroxythiophene, 
2-methylthio-3-cyano-4-hydroxy-5-benzoylthiophene, 
2-n-propylthio-3-cyano-4-hydroxy-5-benzoylthiophene, and 
2-ethylthio-3-cyano-4-hydroxy-5-(4-chlorobenzoyl)thiophene. 
(b) From the compounds obtained according to Example VI (a), the 
4-alkoxythiophenes used for the preparation of compounds (12), (13), (14), 
(23), (24), (25), (41), (55), (59), (74), (75) and (76),mentioned in 
Example I, are prepared as follows: 
Preparation of 2-methylthio-3,5-dicyano-4-methoxythiophene. 
6 g of 2-methylthio-3,5-dicyano-4-hydroxythiophene 10 ml of methyl iodide, 
10 g of potassium carbonate, and 3 ml of triethylamine are refluxed in 300 
ml of acetonitrile while stirring. After 2 hours the reaction mixture is 
filtered warm and evaporated to dryness. The residue is taken up in 200 ml 
of methylene chloride and washed successively with a solution of potassium 
carbonate in water and with water. The methylene chloride solution is then 
dried and evaporated to dryness. After recrystallisation of the residue 
from isopropanol, the desired product is obtained in a yield of 4.0 g; 
melting-point 132.degree. C. 
EXAMPLE VII 
Preparation of 2-ethylthio-3-cyano-4-methyl-5-acetylthiophene. 
To a suspension of 10.5 g of sodium salt of cyanoacetone in 200 ml of 
dimethylformamide 9.0 ml of carbon disulphide are gradually added while 
stirring cooling in ice and keeping under nitrogen, succeeded by 4.5 g of 
sodium hydride dispersion. After stirring for an hour with cooling, 8.4 ml 
of chloroacetone are added dropwise under the same reaction conditions. 
After stirring for another hour, 0.4 g of powdered NaOH are added and 
finally, after again stirring for another 0.5 hour, 8.0 ml of ethyl iodide 
under the same conditions. After stirring, the reaction mixture for again 
another hour and leaving to stand overnight it is poured 1 l of ice water 
and extracted with diethyl ether. The organic phase is washed with water 
three times, dried, treated with charcoal, filtered and evaporated. After 
recrystallisation from isopropanol, the residue yields the desired product 
in a yield of 9.54 g; melting-point 51.degree.-52.degree. C. 
In a corresponding way other 4-alkyl substituted thiophenes are prepared, 
starting substances for the preparation of compounds (56), (62), (63) and 
(91) according to Example I. 
2-Methylthio-3-cyano-4-(4-chlorophenyl)-5-acetylthiophene, starting 
substance for the preparation of compound (6) according to Example I, is 
prepared in a corresponding way, in which, however, in the first reaction 
step dimethyl sulphoxide is used instead of dimethyl formamide as a 
solvent. 
In a corresponding way other 4-aryl substituted thiophenes are prepared. 
starting substances for the preparation of compounds (26), (35), (71) and 
(87) according to Example I. 
EXAMPLE VIII 
Preparation of 2-ethylthio-3-cyano-6-chlorobenzothiophene, starting 
substance for the preparation of compound (20) according to Example I. 
3.62 ml of carbon disulphide are added while stirring, cooling in cold 
water and keeping under nitrogen to a solution of 7.44 g of 
2.4-dichlorophenyl acetonitrile in 80 ml of dry dimethyl formamide, 
succeeded by the gradual addition of 3.6 g of a sodium hydride dispersion. 
After stirring for an hour, 3.20 ml of ethyl iodide are added dropwise 
under the same reaction conditions. The reaction mixture is stirred for 
another hour at room temperature and then 24 hours at 100.degree. C. After 
cooling and pouring into ice water, the formed precipitate is sucked off, 
washed successively with water and petroleum ether, and recrystallised 
from ethanol. The desired product is obtained in a yield of 3.89 g; 
melting-point 91.degree.-93.degree. C. 
The following compounds are prepared in a corresponding manner: 
2-methylthio-3-cyano-4-chlorobenzothiophene. starting substance for the 
preparation of compound (11) according to Example I, and 
2-ethylthio-3-cyano-6-nitrobenzothiophene, starting substance for the 
preparation of compound (27) according to Example I. 
EXAMPLE IX 
The preparation of 
.alpha.-cyano-.beta.,.beta.-bis(methylthio)-3,4-dichlorostyrene, starting 
substance for the preparation of compound (15) according to Example I, and 
.alpha.-cyano-.beta.,.beta.-bis(methylthio)-4-chlorostyrene, starting 
substance for the preparation of compound (19) according to Example I, as 
well as the starting substances for the preparation of compounds (53) and 
(93) according to Example I, is carried out as described by Chauhan et al. 
in Tetrahedron 1976, 32 (14), p. 1779. 
EXAMPLE X 
Preparation of 2-phenylthio-3,5-dicyanothiophene, starting substance for 
the preparation of compound (32) according to Example I and of compound 
(45) according to Example II. 
4.4 ml of thiophenol and 5.0 ml of triethylamine are added, while stirring, 
to a solution of 8.9 g of 2-ethylsulphinyl-3,5-dicyanothiophene, obtained 
according to Example I, in 100 ml of acetonitrile. After leaving to stand 
overnight, the reaction mixture is refluxed for 8 hours. After evaporating 
the solvent, the residue is taken up in methylene chloride and 
chromatographed over a 1 l dry silica gel column. The desired product is 
obtained in a yield of 9.07 g; melting-point 68.degree.-71.degree. C. 
Optionally, any 2-alkylsulphinyl compound may be used as the starting 
substance. 
The following compound is prepared in a corresponding manner: 
2-phenylthio-3,5-dicyano-4-chlorothiophene, starting substance for the 
preparation of compound (82) according to Example I. 
EXAMPLE XI 
Preparation of 2-methylthio-3-cyano-5-methylsulphonylthiophene, starting 
substance for the preparation of compound (60) according to Example I. 
To a solution of 4.36 g of 2-methylthio-3-cyano-5-ethoxycarbonylthiophene, 
obtained according to Example IV (a), in 40 ml of dioxane, is added while 
stirring 40 ml of 2N NaOH. After stirring for two hours the reaction 
mixture is acidified with 45 ml 2N Hcl. The precipitated 
5-carboxythiophene compound is sucked off, washed with water and 
recrystallized from acetonitrile; yield 3.01 g; melting point 
230.degree.-234.degree. C. This 5-carboxythiophene compound in an amount 
of 1.99 g together with 4 ml of quinoline and 0.4 g of Cu-powder is heated 
on 200.degree. C. during approx. 15 minutes. After cooling down, 
diethylether, water and 20 ml 2N Hcl are added. The ether phase is 
separated off, washed with water, dried, decolorized with charcoal, 
filtered and evaporated. 2-Methylthio-3-cyanothiophene is obtained in a 
yield of 0.92 g as an oil; R.sub.f (CH.sub.2 Cl.sub.2)=0.45. The reaction 
is repeated with larger quantities. The last product in an amount of 6.98 
g is added dropwise to a mixture of 7.1 ml of ClSO.sub.3 H and 8.9 g of 
Pcl.sub.5 under stirring and cooling to below 20.degree. C. After stirring 
for half an hour at room temperature, the mixture is poured on ice. The 
formed precipitate is sucked off, washed with water and dissolved in 
methylene chloride. After drying, decolorizing with charcoal, filtration, 
adding diisopropylether and evaporating methylene chloride, the desired 
2-methylthio-3-cyano-5-chlorosulphonylthiophene precipitates in an amount 
of 7.60 g; melting point 112.degree.-115.degree. C. The above 
chlorosulphonyl compound is converted to the corresponding methylsulphonyl 
compound via the corresponding sodium sulphinate by adding 7.50 g to 7.6 g 
of Na.sub.2 SO.sub.3 and 10.1 g of NaHCO.sub.3 in 60 ml of water. While 
stirring the reaction mixture is warmed slowly up to 70.degree. C. and 
stirred at 70.degree. C. for half an hour. To the solution obtained 3.75 
ml of methyl iodide is added; reflux for 5 hours. After evaporating the 
volatile components in vacuo, the formed precipitate is sucked off, washed 
with water and recrystallized from methanol. 
2-Methylthio-3-cyano-5-methylsulphonylthiophene is obtained in a yield of 
2.88 g; melting point 126.degree.-128.degree. C. 
In a corresponding way is prepared 
2-ethylthio-3-cyano-4-chloro-5-methylsulphonylthiophene, starting compound 
for the preparation of compound (77) according to Example I and of 
compound (84) according to Example II. 
EXAMPLE XII 
Preparation of 2-ethylthio-3,5-dicyano-4-phenoxythiophene, starting 
substance for the preparation of compound (94) according to Example I. 
Phenol in an amount of 2.82 g is dissolved in 30 ml of methanol comprising 
0.69 g of sodium. After adding 50 ml of dimethylformamide the methanol is 
evaporated. The residual solution is added while stirring to a solution of 
6.86 g of 2-ethylthio-3,5-dicyano 4 -chlorothiophene, obtained according 
to Example IV (b), in 40 ml of dimethylformamide. After stirring for one 
hour, the reaction mixture is poured on 0.5 l of ice water. The formed 
precipitate is sucked off, washed with water and dissolved in methylene 
chloride. The solution is washed with a bicarbonate solution, dried, 
filtered, supplied with diisopropylether and evaporated partially. The 
crystallized 2-ethylthio-3,5-dicyano-4-phenoxythiophene is sucked off; 
yield 5.78 g; melting point 111.degree.-112.degree. C. 
In a corresponding way 2-methylthio-3,5-dicyano-4-phenylthio-thiophene, 
starting substance for the preparation of compound (85) according to 
Example I, is prepared. 
EXAMPLE XIII 
Preparation of 2-ethylthio-3,5-dicyano-4-(1,2,4-triazol-1-yl)thiophene, 
starting substance for the preparation of compound (68) according to 
Example I. 
Sodium in an amount of 0.69 g is dissolved in 30 ml of methanol. After 
adding 30 ml of dimethylformamide the methanol is evaporated and 2.07 g of 
1,2,4-triazole in 30 ml of dimethylformamide is added. Under stirring and 
flushing with nitrogen the mixture is refluxed for 1.5 hours. After 
cooling in ice/acetone a solution of 6.86 g of 
2-ethylthio-3,5-dicyano-4-chlorothiophene, obtained according to Example 
IV (b), in 40 ml of dimethylformamide is added and the reaction mixture is 
stirred overnight. After pouring out in 0.5 1 of ice-water the formed 
precipitate is sucked off washed with water and dissolved in methylene 
chloride. The organic phase is dried, decolorized with charcoal, filtered, 
partially evaporated and supplied with diisopropyl ether. The desired 
2-ethylthio-3,5-dicyano-4-(1,2,4-triazol-1-yl)thiophene precipitate is 
sucked off, washed with diisopropyl ether and dried; yield 4.30 g; melting 
point 148.degree.-151.degree. C. 
In a corresponding way 2-ethylthio-3,5-dicyano-4-(imidazol-1-yl)thiophene, 
starting substance for the preparation of compound (69) according to 
Example I, is prepared. 
EXAMPLE XVI 
(a) Preparation of a solution of an active substance, viz. 
2-methylsulphinyl-3-cyano-5-acetylthiophene (1), in a water-miscible 
liquid ("liquid"). 
10 g of the above active substance are dissolved in a mixture of 10 ml of 
isophorone and approx. 70 ml of dimethylformamide, after which 
polyoxyethylene glycol ricinyl ether as an emulsifier is added in a 
quantity of 10 g. 
The other active substances are processed in a corresponding manner to 10 
or 20% "liquids". 
In a corresponding manner, "liquids" are obtained in N-methyl pyrrolidone, 
dimethyl formamide, and a mixture of N-methyl pyrrolidone and isophorone 
as solvents. 
(b) Preparation of a solution of the active substance in an organic 
solvent. 
200 mg of the active substance to be investigated are dissolved in 1,000 ml 
of acetone in the presence of 1.6 g of nonylphenol polyoxyethylene. After 
pouring in water, this solution can be used as a spraying liquid. 
(c) Preparation of an emulsifiable concentrate of the active substance. 
10 g of the active substance to be investigated are dissolved in a mixture 
of 15 ml of isophorone and 70 ml of xylene; 5 g of a mixture of a 
polyoxyethylene sorbitan ester and an alkylbenzene sulphonate are added to 
this solution as an emulsifier. 
(d) Preparation of a dispersible powder (W.P.) of the active substance. 
25 g of the active substance to be investigated are mixed with 68 g of 
kaolin in the presence of 2 g of sodium butyl naphthalene sulphonate and 5 
g of lignine sulphonate. 
(e) Preparation of a suspension concentrate (flowable) of the active 
substance. 
A mixture of 10 g of active substance, 2 g of lignine sulphonate, and 0.8 g 
of sodium alkyl sulphate is supplied with water to a total quantity of 100 
ml. 
(f) Preparation of a granule of the active substance. 
7.5 g of active substance, 5 g of sulphite lye, and 87.5 g of ground 
dolomite are mixed, after which the resulting mixture is processed to a 
granular composition by means of the so-called compacting method. 
EXAMPLE XV 
Test with respect to the protection of seedlings against a plant pathogenic 
seed fungus, namely Fusarium culmorum, by means of a seed treatment. 
Wheat seed, infested with Fusarium culmorum, is treated with the substance 
to be tested in the form of a composi tion in a quantity of 3 g per kg of 
seed. The composition is obtained by pulverising the substance to be 
tested and then intimately mixing with kaolin in a concentration of 10% by 
weight. The seed thus treated is sown in a tray containing soil which is 
placed in a Wisconsin tank with a bottom temperature of 
8.degree.-12.degree. C. After three weeks the number of emerged and 
healthy plants is determined. The emergence of healthy plants from 
untreated seed serves as control. For comparison, the known substances 
2-methylsulphinyl-4-methyl-5-nitrothiazole (a), 
2-methylsulphinyl-3-nitrothiophene (b) and 
2-ethylsulphinyl-3-nitro-5-acetylthiophene (c) mentioned hereinbefore are 
also tested. The results are recorded in Table A below. In the examples, 
the numbers of the compounds refer to the specification. 
TABLE A 
______________________________________ 
Percentage of emerged, 
Compound No. healthy plants 
______________________________________ 
(1) 91 
(2) 87 
(3) 91 
(4) 90 
(5) 85 
(7) 98 
(8) 92 
(9) 85 
(10) 98 
(12) 93 
(13) 90 
(14) 87 
(27) 96 
(a), known 68 
(b), known 75 
(c), known 74 
untreated 67 
______________________________________ 
EXAMPLE XVI 
Test with respect to the protection of seedlings against a plant-pathogenic 
soil fungus, namely Pythium spp., by means of a seed treatment. 
The compounds to be tested are processed to compositions by pulverising 
them and then mixing them intimately with kaolin in the desired 
concentration (see Table B). Beet seed is treated with these compositions 
in a quantity of 6 g of composition per kg of seed and then sown in trays 
with soil which was seriously infested with Pythium spp. After 3 weeks in 
a glass-house at 18.degree.-22.degree. C. and a relative humidity of 
70-100%, the percentage of non-emerged and diseased seedlings 
(damping-off) is determined. The results are recorded in Table B. For 
comparison, the known substance 2-methylsulphinyl-4-methyl-5-nitrothiazole 
(a) is also tested. 
TABLE B 
______________________________________ 
Dosage in mg of 
active substance 
percentage 
Compound No. per kg of seed 
damping-off 
______________________________________ 
(1) 600 8 
1200 7 
(2) 600 7 
1200 6 
(3) 600 6 
1200 5 
(4) 600 10 
1200 9 
(5) 600 21 
1200 17 
(7) 600 17 
1200 17 
(8) 600 16 
1200 12 
(9) 600 15 
1200 11 
(10) 600 10 
1200 9 
(12) 600 0 
1200 0 
(13) 600 3 
1200 1 
(14) 600 23 
1200 20 
(27) 600 4 
1200 2 
(a), known 600 57 
1200 45 
untreated -- 72 
______________________________________ 
EXAMPLE XVII 
Toxicity with respect to warm-blooded living beings. 
Lethal dose 
The LD.sub.50 is determined by orally administering the substance to be 
tested to male mice and determining the acute mortality. In Table C below, 
the LD.sub.50 is recorded in mg/kg of body weight. 
For comparison, the known compound (b) (see EXAMPLE XV) is also tested. 
TABLE C 
______________________________________ 
Compound No. LD.sub.50 (mg/kg) 
______________________________________ 
(7) 400 
(8) 119 
(10) 141 
(13) 130 
(33) 246 
(43) 246 
(b), known 31.6 
______________________________________ 
EXAMPLE XVIII 
Toxicity with respect to warm-blooded living beings. 
The mutagenity is determined by means of the so-called Ames test. The Ames 
test is carried out under the conventional standard conditions on the 
Salmonella typhimurium strain TA 100, both without metabolic activation 
(-S9) and with metabolic activation (+S9). The results are recorded in 
Table D. For comparison, the known compound (c) (see EXAMPLE XV) is also 
tested. 
TABLE D 
______________________________________ 
Ames Test 
Compound No. -S9 +S9 
______________________________________ 
(5) - - 
(7) - - 
(8) - - 
(9) - - 
(10) - - 
(12) - - 
(13) - - 
(23) - - 
(40) - - 
(44) - - 
(c), known + + 
______________________________________ 
EXAMPLE XIX 
In vitro test on activity against Pyrenophora graminea. 
The compound to be tested is processed in a culture medium consisting of 1% 
by weight of glucose, 0.2% by weight of a yeast extract (marmite), 0.5% by 
weight of a protein (pepton), 2.5% by weight of agar-agar, and 95.8% by 
weight of water, in petri dishes in concentrations of 3 and 10 ppm. The 
petri dishes are inoculated with the plant-pathogenic fungus Pyrenophora 
graminea and then kept at a temperature of 20.degree. C. After 48 hours 
the growth-inhibiting activity of the compounds is determined visually. 
For comparison, the known substance (b) (see EXAMPLE XV) is also tested. 
The results are recorded in Table E. 
TABLE E 
______________________________________ 
Concentration 
% growth inhibition 
Compound No. in ppm of the fungus 
______________________________________ 
(2) 3 64 
10 79 
(3) 3 57 
10 80 
(4) 3 66 
10 84 
(5) 3 54 
10 89 
(6) 3 54 
10 77 
(7) 3 59 
10 83 
(8) 3 49 
10 72 
(31) 10 77 
(33) 10 83 
(35) 10 76 
(39) 10 81 
(43) 10 72 
(47) 10 74 
(51) 10 71 
(52) 10 71 
(53) 10 83 
(66) 10 84 
(72) 10 70 
(78) 10 86 
(79) 10 80 
(82) 10 80 
(85) 10 73 
(86) 10 76 
(94) 10 70 
(b), known 3 0 
10 37 
control -- 0 
______________________________________ 
EXAMPLE XX 
Compounds according to the invention are tested on Fusarium culmorum in the 
same manner as described in EXAMPLE XIX. The following compounds cause at 
least 75% growth inhibition of the fungus in a concentration of 30 ppm: 
(2), (3), (5), (7), (11), (12), (13), (14), (19), (22), (23), (27), (29), 
(31), (32), (33), (34), (35), (36), (37), (38), (39), (40), (41), (42), 
(43), (44), (45), (47), (51), (52), (53), (55), (57), (58), (61), (62), 
(64), (65), (67), (71), (72), (73), (74), (75), (78), (79), (80), (81), 
(82), (85), (86), (87), (88), (89), (90), (91), (92), and (93). 
EXAMPLE XXI 
Compounds according to the invention are tested on i Leptosphaeria nodorum 
in the same manner as described in EXAMPLE XIX. The following compounds 
cause at least 85% growth inhibition of the fungus in a concentration of 
30 ppm: (2), (3), (4), (5), (7), (9), (10), (12), (13), (14), (15), (17), 
(19), (20), (23), (27), (31), (32), (33), (34), (35), (36) (37) (40), 
(41), (42), (43), (44), (45), (47), (51), (53), (58), (63), (64), (65), 
(67), (71), (72), (73), (74), (75) (76), (85), (86), (87), (88), (89), 
(92) and (94). 
EXAMPLE XXII 
Compounds according to the invention are tested on Pythium splendens in the 
same manner as described in EXAMPLE XIX. The following compounds cause at 
least 95% growth inhibition of the fungus in a concentration of 10 ppm: 
(1). (2), (3), (4), (5), (6), (7), (8), (9), (10), (12), (13), (14), (15), 
(16), {17), (18), (19), (21), (22), (25), (26). (27), (28), (30), (31), 
(32), (33), (34), (35), (36), (39), (40), (41), (42), (43), (45), (46), 
(47), (48), (49), (50), (51), (52), (54), (55), (56), (57), (58), (59), 
(60), (61 ). (66), (67), (68), (69), (70), (72), (74), (77), (78), (79). 
(80), (82), (83), (84), (85), (86), (89), (93) and (94). 
EXAMPLE XXIII 
Compounds according to the invention are tested on Rhizoctonia solani in 
the same manner as described in EXAMPLE XIX. The following compounds cause 
at least 75% growth inhibition of the fungus in a concentration of 30 ppm: 
(2), (3), (4), (15), (19), (27), (33), (34), (36), (39), (42), (43), (52), 
(80) and (85),