SU1496633A3 - Method of producing thiophene derivatives - Google Patents

Abstract

The invention relates to heterocyclic compounds, in particular to the preparation of thiophene derivatives SC (R ₁ ) = C (R ₂ ) -CX = C (S (O) _N (R)), where RC ₁ -C ₁₂ is alkyl, alkenyl or C ₂ -C ₄ - alkynyl phenyl or benzyl

R ₁ is cyano or formyl or alkylcarbonyl or C ₁ -C ₄ alkoxycarbonyl

R ₂ -H, halogen, unsubstituted or substituted by one or two C ₁ -C ₄ - alkyl groups and / or alkylcarbonyl group C ₂ - C ₅ amino group, or triazolyl, imidazolyl, C ₁ -C ₄ alkyl, unsubstituted or substituted C ₂ -C005 alkylcarbonyl C ₁ -C ₄ - alkoxy, or unsubstituted or substituted by halogen, phenoxy or phenylthio phenyl

or R ₁ and R ₂ , together with the carbon atoms to which they are bonded, means unsubstituted or halogen or nitro substituted phenyl

X-cyano or formyl group

n = 1 - 2, which have fungicidal and bactericidal activity. The purpose of the invention is to develop a method for the preparation of compounds having the indicated activity. The preparation of the target compounds is carried out by the oxidation of the corresponding thio compounds. 3 tab.

Description

This invention relates to a process for the preparation of new thiophene derivatives, which have fungicidal and bactericidal activity, and can be used in agriculture.

The purpose of the invention is to develop a process for the preparation of new thiophene derivatives, which are more highly effective than the known analogues.

Example 1. Preparation of 2-methylsulfinyl-3-diano-5-acetylthiophene (1)

5.0 g of 83% m-chlorobenzoic acid is gradually added, with stirring, over 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 a further 30 minutes at 5 ° C, a saturated solution of sodium bicarbonate is added in approximately 50 ml of water (then the reaction mixture is stirred for 60 minutes. Organic

with

O5 05 00 00

CN

1A

the layer is separated, washed with water and dried. After distilling off the solvent, the desired product is obtained with a yield of 4.6 g; m.p. 150 ° C.

In an appropriate way, optionally using p-nitrobenzoic acid as the oxidizing agent and chloroform as the solvent, compounds are obtained, the data for which are given in Tables 1 and 2.

And p and. measure 2. Preparation of 2-ethyl sulfonyl-3,5-dicyanothiophene (16).

2 ml of 35% hydrogen peroxide is added to a solution of 1.62 g of 2-ethylthio-3,5-dicyantiophene in 50 ml of acetic acid. After heating at a temperature of approximately 100 ° C for approximately 1 hour, another 1 ml of 35% hydrogen peroxide is added, followed by heating for another 1 hour at approximately 100 ° C. After cooling, the substance crystallizes, the crystals are drained, and after washing with ethanol The required compound with a yield of 1.49 rj i. 121-124.

The following compounds were prepared accordingly:

Connection WITH

18138-140

21 115-117

22140-143 45 189-191.

84216-218

89119-121

Table 3 shows the codes for all connections.

Receive the following tio compounds according to the proposed method according to

examples:

(1) 2-Methylsulfinyl-3-cyano-5-α-acetylthiophene

(2) 2-methylsulfinyl-5-cyano-4-chloro-5-acetylthiophene;

(3) 2-methylsulfinyl-3, 5-dicyano-4-chlorothiophene,

(4) 2-methylsulfinyl-3,5-dicyano thiophene,

(5) 2-ethylsulfinyl-3-cyano-4- - chloro-5-acetylthiophene

(6) 2-methylsulfinyl-3-diano-4- - (4-chlorophenyl) -5-acetylthiophene;

(7) 2-ethylsulfinyl-3,5-dI1-shano-4-chlorothiophene;

(8) 2-ethylsulfinyl, -3,5-dicyanothiophenol

(9) 2-methylsulfinyl-3-11, ianp-5-acetylthiophene;

(10) 2-ethylsulfinyl-3-cyano-4-amino-5-acetylthiophene;

(11) 2-methylsulfinyl-3-cyano-4-chlorobenzothiophene;

(12) 2-methylsulfinyl-3, 5-dicyan-4-methoxythiophene;

(13) 2-ethylsulfonyl-3,5-didano-4-methoxythiophene,

(14) 2-methylsulfinyl-3,5-dicyano-4-ethoxythiophene,

(15) o6-cyano-B-methylsulfinyl-B- -methylthio-3,4-dichloro-styrene;

(16) 2-ethylsulfonyl-3,5-dicyano thiophene}

(17) 2-ethylsulfinyl-3-cyano-4- -Y-methylamino-5-acetylthiophene;

(18) 2-ethylsulfokyl-3-cyano-4-chloro-5-acetylthiophene;

(19) o (.- cyano- (3-methylsulfinyl-B-methylthyo-4-chlorostyrene)

(20) 2-methylsulfinyl-3-cyano-6-chlorobenzothiophene,

(21) 2-ethylsulfonyl-3-cyano-5-acetylthiophene,

(22) 2-ethylsulfonyl-3, 5-dicyano-4-chlorothiophene

(23) 2-ethylsulfinyl-3-cyano-4-methoxy. And 5-acetylthiophene i

(24) 2-propargylsulfinyl-3,5-β-dicyano-4-methoxythiophene,

(25) 2-methylsulfinyl-3-cyano-4-methoxy-5-acetylthiophene

(26) 2-methylsulfinyl-3-cyano-4- - (4-hporfensh1) -5-formylthiophene

(27) 2-ethylsulphinyl-3-cyano-6- -nitrbenzothiophene;

(28) 2-methylsulfonyl-3-cyano-5-α-formylthiophene;

(29) 2-methylsulfinyl-3-cyano-4-amino-5-ethoxycarbonylthiophene;

(30) 2-metshlsulfinil-3-cyano-5-benzoylthiophene

(31) 2-methylsulfinyl-3-cyano-4-chloro-5-benzoylthiophene

(32) 2-Phenylsulfinyl-3,5-dicyan thiophene

(33) 2-n-propylsulfinyl-3, 5-dicyano-4-5Sortiofen1

(34) 2-n-hexylsulfinyl-3,5-dicyano-4-chlorothiophene

(35) 2-methylsulfinyl-3, 5-dicyan -4- (4-chlorophenylphenyl) thiofen,

(36) 2-n-octylsulfinyl-3,5-dicyano-4-chlorothiophene;

(37) 2-ethylsulfinyl-3-cyano-4-chloro-5-ethoxycarbonylthiophene;

(38) 2-n-hexylsulfinyl-3,5-dicyano-4-aminothiophene.

(39) 2-n-butylsulfinyl 3-cyano-4-chloro-5-acetylthiophene,

(40) 2-n-propylsulfinyl-3, 5-di cyanothiophene,

(41) 2-n-butylsulfinyl-3, 5-dicyano-4-methoxynthisphene,

(42) 2-methylsulfinyl-3-cyano-4-chloro-5- (4-chlorobenzoyl) thiophene;

(43) 2-n-butylsulfinyl-3, 5-dicyano-4-chlorothiophene;

(44) 2-n-butylsulfinyl-3-cyano-5-acetylthiophene;

(45) 2-phenylsulfonyl-3, 5-dicyan thiophene,

(46) 2-ethylsulfinyl-3, 5-dicyano-4-aminothiophene;

(47) 2-ethylsulfinyl-3-cyano-5- (4-chlorobenzoyl) thiophene;

(48) 2-methylsulfinyl-3-cyano-4-amino-5-formylthiophene

(49) 2-ethylsulfinyl-3-11-iano-4-amino-3-formylthiophene;

(50) 2-ethylsulfinyl-3-cyano-4-chloro-5-formylthiophene;

(51) 2-methylsulfinyl-3-cyano-5- -benzoylthiophene

 (52) 2-methylsulfinyl-3-cyano-5- (4-chlorobenzoyl) thiophene

(53) o (, - cyano-B-ethylsulfinyl-6-ethylthio-4-chlorostyrene;

(54) 2-ethylsulfinyl-3, 5-dicyano-4- (P-acetyl-P-methylamino) thiophene,

(55) 2-n-propylsulfinyl-3, 5- -dicyano-4-methoxythiophene;

(56) 2-ethyl 1-sulfinyl-3-cyano-4-methsl-5-formylthiophene;

(57) 2-n-propylsulfinyl-Z-cyano -4-amino-5-acetylthiophene

(58) 2-n-butylsulfinyl-3-cyano-4-amino-5-acetylthiophene;

(59) 2-methylsulfinyl-3-cyano-4- -acetylmethoxy-5-acetylthiophene;

(60) 2-methylsulfinyl-3-cyano-5-methylsulfonyl thiophene,

(61) 2-n-propylsulfinyl-Z-cyano-4-chloro-5-acetylthiophene,

(62) 2-n-propylsulfinyl-3-cyano-4-methyl-5-adylthiophene

(63) 2-ethylsulfinyl-3,5-dicyano-4-m e ty lithi of e n,

(64) 2-ethylsulfinyl-3-cyano-5-benzoylthiophene;

(65) 2-ethylsulfinyl-3-cyano-4-aa shno-5-benzoylthiophene;

(66) 2-ethylsulfinyl-3-cyano-4-amino-5- (4-chlorobenzoyl) thiophene,

(67) 2-n-propylsulfinyl-Z-cyano-4-amino-5-benzoylthiophene;

1496633

(68) 2-ztilsulfi1dal-3,5-dicyapo-. -4- (1,2,4-triazol-1-yl) thiophene;

(69) 2-ethylsulfinyl-3, 5-dicyano-g-4- (imidazol-1-yl) tis phen;

(70) 2-methylsulfinyl-3, 5-diformylthiophene {

(71) 2-ethylsulfinyl-3, 5-dicyano-4-phenylthiophene

0 (72) 2-ethylsulfinyl-3-cyano-4-chloro-5- (4-chlorobenzoyl) thiophene}

(73) 2-n-propylsulfinyl-3-cyano-5- (4-chlorobenzoyl) thiophene;

(74) 2-methylsulfinyl-3-cyano-4-5-methoxy-5-benzoylthiophene

(75) 2-n-propylsulfinyl-3-cyano-4-methoxy-5-benzoyl thiophene,

(76) 2-ethylsulfinyl-3-cyano-4-methoxy-5- (4-chlorobenzoyl) thiophene;

0 (77) 2-ethylsulfinyl-3-cyano-4-t-chloro-5-methylsulfonylthiophene

(78) 2-benzylsulfinyl-3, 5-dicyano-4-chlorothiophene;

(79) 2-n-butylsulfinyl-3, 5-di-5 cyano-4-bromothiophene,

(80) 2-n-butylsulfinyl-3, 5-dicyanothiophene;

(81) 2-n-othylsulfinyl-3, 5-dicyano thiophene,

O (82) 2-phenylsulfinyl-3,5-dicyano-4-chlorothiophene,

(83) 2-ethylsulfinyl-3, 5-diformyl-4-chlorothiophene;

(84) 2-ethylsulfonyl-3-cyano-4-chloro-5-methylsulfoNylthiophene

(85) 2-methylsulfins-3, 5-dicyano-4-phenylthiophene

(86) 2-n-butylsulfinyl-3-cyan-4-bromo-5-acetylthiophene;

(87) 2-ethylsulfinyl-3-cyano-4-phenyl-5-acetylthiophene;

(88) 2-n-Butylsulfinyl-3-cyano-4-amino-5-benzoylthiophene

(89) 2-n-butylsulfonyl-3,5-dicyano-4-bromothiophene;

(90) 2-n-butylsulfinyl-3-cyano-5-benzoylthiophene;

(91) 2-ethylsulfinyl-3-cyano-4-methyl-5-benzoylthiophene

0 (92) 2-ethylsulfinyl-3-cyano-4-chloro-5-benzoylthiophene,

(93) o6-cyano-L-methylsulfinyl- [3-methylmetiostirol, E-isomer;

(94) 2-ethylsulfinyl-3, 5-dicyano-4-phenoxythiophene. ,

five

0

five

five

Example 95. The study of the protection of seedlings from plant pathogenic fungi transmitted from seeds Example 96. The study of the protection of inputs from plant pathogenic fungi xc through the soil, namely Pythium spp, by treating the seeds.

Test compounds are processed in the composition by spraying

Unprocessed

72

Example 97. Toxicity to warm-blooded living beings.

Lethal dose.

 determined by oral administration of the test substance to male mice and determination of sudden death. Table 3 shows the LD mg / kg live weight.

Also known compound (b) was tested for comparison.

Table 3

49663310

Example99. In vitro activity test with respect to Pyrehoprop graminea.

 The test compound is treated in a culture medium consisting of 1 wt.% Glucose, 0.2 wt.% Yeast extract (marmite), 0.5 wt.% Protein (pentone), 2.5 wt.% Agar-10 agar and 95.8% by weight of water in Petri dishes at a concentration of 3 and 10 ppm Petri dishes are infected with pathogenic to plants Rughophosphora graminea fungi and then harvested 15 at. After 48 hours, the growth activity of the compounds is determined visually. Comparison test also known compound (b). The results are shown in table.5.

Example 98. Toxicity to warm-blooded living beings.

Mutagenism is defined by the so-called Ames test. The Ames test is carried out under the usual standard conditions on the Salmonella typimurium TA100 strain both with metabolic activation (+ S9) and without it (). The results are shown in table 4.

Also known compound (c) was tested for comparison.

Table 5

25

(2) (3) (4)

Continuation of table.5

Control

Example 100. The proposed compounds are tested on Fusarium culmorum in the same manner as described in Example 99. The following compounds cause at least 75% inhibition of the growth of fungi at a concentration of 30 ppm: (2), (3), (5) , (7), (11). (12), (14), (19), (22), (23), (27), (29), (31), (32), (38), (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), (90), (91), (92) and (93).

EXAMPLE 101 The proposed compounds were tested on Leprosphaeria nodorum in the same manner as described in Example 99. The following compounds cause at least 85% inhibition of fungal growth at a concentration of 30 ppm: (2) (3), (4), (5), (7) -, (9), (10), (12), (13), (14), (15), (19), (20), ( 23). (27), (33), (34), (35), (36), (41), (42), (43), (44), (51), (53), (58), (63 ), (67) i (71), (72), (73), (76), (85), (86), (87) i (92) and (94).

(31), (32),

(37), (40),

(45), (47),

. (64), (65),

(74), (75),

(88), (89),

Example 102: Proposed compounds were tested on Pythium splenensors in the same manner as described in Example 99. The following compounds cause at least 95% inhibition of fungal growth at a concentration of 10 MD: (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 103. The proposed compounds were tested for Rhigoctonia solani in the same manner as described in Example 99. The following compounds cause at least 75% inhibition of the growth of fungi at a concentration of 30 MD: (2), ( 3), (4), (15), (19), (27), (33), (34), (36), (39), (42), (43), (52), (80) and (85).

Table.6

131496633

Prolzheine table.6

Table 7

As can be seen from the above tests, the proposed compounds possess

15

higher activity than known.

Claims (1)

Invention Formula The method of obtaining the thiophene derivatives of the formula B2 B : S (0) n  R with 1-12 carbon atoms, where R is alkyl Yes, alkenyl or alkyne, with 2-4 carbon atoms, phenyl or benzyl, R is cyano or formyl, or alkylcarbonyl, or alkoxycarbonyl with 2-5 carbon atoms, unsubstituted or substituted with halogen benzoyl, or alkylsulfonyl with 1-4 carbon atoms; Editor S. Patrushev Compiled by T. Vlasov Tehred L. Oliynyk Proofreader; E.Lonchakova Order 4291/59 Circulation 352 VNIIPN State Committee for Inventions and Discoveries at the State Committee on Science and Technology of the USSR, 113035, Moscow, Zh-35, 4/5 Raushsk Nab. . „," .. -. ", - - - -. -. - - - -" ..... - - - .. - ". and - .. in .. ™ "- - ....-.-- --i-. ™ - -.v .--." .. Production and publishing plant Patent, Uzhgorod, st. Gagarin, 101 - 496633. sixteen Rj is hydrogen, halogen, unsubstituted or substituted by one or two alkyl groups with 1-4 atoms with a carbon and / or alkylcarbonyl group with 2-5 carbon atoms, an amino group, or triazolyl, imidazolyl, alkyl with 1-4 carbon atoms, unsubstituted or substituted alkylcarbonyl with 2-5 carbon atoms, alkoxyl with 1-4 carbon atoms, or unsubstituted or phenyl substituted by halogen, phenoxy or phenylthio, or R and, together with carbon atoms 15 (the genus to which they are bonded, means unsubstituted or substituted phenyl, or halogen or nitro, X, is a cyano or formyl group; n 1-2, 20 wherein the corresponding thio compound is subjected to oxidation. Subscription