前苏联专利SU1570648A3 Method of obtaining derivative of 1-heterocyclyl-1h-imidazole-5-carboxylic acid, its salt or stereoc

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专利摘要:
1-Benzoheterocyclyl-1H-imidazole -3-carboxylic acid derivs. of formula (I) and their salts and quat. derivs. and their N-oxides are new. In the formula R1 = H or SH; R2 = H, 1-7C alkyl, 3-7C alkenyl, 3-7C alkynyl, 3-7C cycloalkyl, (1-7C)alkoxy-(1-7C) alkyl or aryl-(1-5C)alkyl; n = 0, 1 or 2; Y = S(O)m-CH2, O-CH2, N(E)-CH2 or N=CH, the heteroatom being linked to the C atom of the benzene ring; m = 0, 1 or 2; E = H, 1-5C alkyl, 1-5C alkanoyl or p-MeC6H4SO2; R3-R6=H, 1-6C alkyl, mono- or di-aryl-(1-5C)alkyl, 1-6C alkoxy, halogen, 3-7C alkenyl 1-5C alkyl or 1-5C alkoxy each substd. with 1-3 halogens or aryl; or R3+R4 = residue of a fused benzene ring opt. substd. by 1 or 2 H, 1-5C alkyl, 1-5C alkoxy, halogen, 1-5C alkyl or 1-5C alkoxy both substd. by 1-3 halogens, NO2, NH2 or NH-CPG; or when R3+R4 are geminally substd. they form a 3-7C spirocyclic C ring; R7, R8 = H, 1-5C alkyl, 1-5C alkoxy, halogen, 1-5C alkyl or 1-5C alkoxy both substd. by 1-3 halogens, CN, NO2 NH2, mono-or di-(1-5C) alkylamino or NH-COG; G = 1-6C alkyl; aryl = Ph opt. substd. by 1-3 halogen, 1-5C alkyl or 1-5C alkoxy. R3-R6 may be present on any C atom of the Y-contg.part of the bicyclic ring, including the CH2 or CH gps. of the (CH2)n, S-CH2, 0-CH2, N(E)-CH2 or N=CH.
公开号:SU1570648A3
申请号:SU874202081
申请日:1987-02-26
公开日:1990-06-07
发明作者:Розалия Эжен Ван Ломмен Ги；Лутз Вильям；Франс Элизабета Ван Гестель Йозеф
申请人:Жансен Фармасетика Н.В.(Фирма)；
IPC主号:

专利说明:

bathe with an alkali metal isothiocyanate to form compound IV, which is reacted with sodium nitrite in the presence of nitric acid in water to isolate the desired product with RH, or transfer it (when R, -H or mercapto group) to the salt by treatment with acid or by base, or by isolation of the desired product in the form of its stereochemically isomeric form. Herbicide
activity in relation to the palmate, m tly, chicken millet, corn reaches 85%. The structure of compounds f-ly II, III and IV:
Ii) H-C (0) -ZH-SNg-C (o) -OK2;
Iii) H-C (0) -NK-C C (0) ORZ3 HC-0-Z;
lo iv) (0) (SH) -tiK,
where R, K cm, above; Z is an alkali metal atom. 13 tab.
The invention relates to a process for the preparation of new, with herbicide activity, derivatives of 1-heterocyclyl-H-imidazole-5-carboxylic acids of
The purpose of the invention is the synthesis of new compounds in their herbicidal activity superior to the structural analogue, also having herbicidal activity
Example 1 a) Mixture 220mae, h. 1 - (5-fluoro-2-hydroxy) ethane, 125. 3-methyl 2-butanone, 53 pyrrolidine and 396 May „h, methylbenzene is first stirred for three days at room temperature, and then heated for 4 hours with a reflux condenser using a water separator. After cooling, the reaction mixture is washed with a sodium hydroxide solution. The precipitated product is filtered off and set aside. From the filtrate, the organic layer is washed with a solution of hydrochloric acid, dried, filtered and evaporated. The residue and the precipitated product, which was set aside, are placed in methanol and activated carbon is added. The contents of the reaction vessel are filtered through reflux and the filtrate is evaporated. The residue is purified by silica gel column chromatography using trichloromethane as eluant. Pure fractions are collected and the eluent is evaporated. The residue is distilled and obtained 66 May. (20.5%) 6 fluoro-2, 3-dihydro-2-methyl-2- (1-methylethyl) -4H-1-b, benzopyran-4-one; t. Kip, 95-105 ° C at 35ZOP
b) To a stirred mixture of 66 mph. 6-fluoro-2EZ-dihydro 2-me0
five
0
five
0
five
Tyl-2 (1-methylethyl) -4H-1-benzopyran-4-one, 30 ma.ch, hydroxylamine hydrochloride, 128 wt.h. ethanol and 160 parts by weight of water were added 36 parts by weight. sodium carbonate at 60 ° C. The reaction mixture is stirred and refluxed for three days. Add 160 wt.h. water. After cooling, cichloromethane is added and the reaction mixture is filtered through diatomaceous earth. The organic layer is dried, filtered and evaporated. The residue is placed in methylbenzene, the latter is evaporated and 68 wt.h. (95.5%) oxide (E + g) -6-fluoro-2, 3-dihydro-2-methyl-2- (1-methylethyl) -4H-1-benzopyran-4-one.
c) A mixture of 68 parts by weight, oxime (E + Z) - -6-fluoro-2,3-dihydro-2-methyl-2- (1-methylethyl) -4I-1-benzopyran-4-one and 400 wt. . h. methanol, saturated with ammonia, hydrogenated at normal pressure and room temperature with 50 wt.h. Nickel catalyst Ren. After the calculated amount of hydrogen is taken up, the catalyst is filtered off and the filtrate is evaporated. The residue is taken up in dichloromethane to dissolve and activated charcoal is added. The mixture is filtered through diatomaceous earth. The organic layer is separated from the filtrate, dried, filtered and evaporated. The residue is dissolved in 1,1-hydroxy-bis-ethane and hydrogen chloride gas is bubbled through the solution. The precipitate is filtered off and dissolved in a mixture of water and dichloromethane. The contents of the reaction vessel are alkalinized with sodium hydroxide solution. The separated organic layer is dried, filtered and evaporated. Get
44 mach. (70.4%) (cis + trans) -6- -fluoro-2,3-dihydro-2-methyl-2- (1-methyl ethyl) -4H- -beneopyran-4-amine as a residue (compound 10 , 34)
d) Mixture 44 mac. (cis + trans) - -6-fluoro-2,3-dihydro-2-methyl-2- (1-methylethyl) -4H-1-benzopyran-4-amine,
19 ma.ch. methyl ester of chloroacetic acid, 21 wt.h. H, K-diethyl-ethanamine and 31.5 wt.h. The M, M-dimethylformamide is left under stirring overnight at room temperature. After adding 1,1-hydroxy-bis-ethane, the precipitate is filtered,
the filtrate is washed 4 times with water, dried, filtered and evaporated. The residue is purified by column chromatography on silica gel using trichloromethane as eluent.
Pure fractions are collected, the eluent is evaporated and receive 50 wt.h. (84.6%) methyl (cis + trans) -N-b-fluoro-2,3-di-hydro 2-methyl-2- (1-methylethyl) -4H-1-benzopyran-4-shG glycine in as a residue (compound 9.37).
d) A mixture of 50 wt.h. methyl (cis +
+ trans) -N-b-fluoro-2, 3-dihydro-2-methyl-2- (1-methylethyl) -4H-1-benoopyran-4-yl 1 glyiine, 9.6 wt.h. formic acid and 54 wt.h. The dimethyl benzene is stirred and heated under reflux for 5 hours using an aqueous separator (formic acid is added several times). After cooling, the reaction mixture was successively washed with a 20% solution of formic acid, soluble sodium carbonate and twice with a solution of sodium chloride, after which dichloromethane was added. The organic layer is dried, filtered and evaporated. The residue is crystallized from 2,2-oxy-bis-propane. The product is filtered off, dried in vacuum at 40 ° C and receive 30 wt.h. (54.6%) (cis-trans) -fluoro-2,3-dihydro-2-methyl-2- (1-methylethyl) -4H-1-benzopyra-n-4-ShO-1T- methyl ester - formylglycine, so pl. 115.4 ° C (comp. 8.37).
e) To a stirred mixture of 28 wt.h. methyl- (cis + trans) -N-b-fluoro-2,3-di-hydro-2-methyl-2- (1-methylethyl) -4H-1-benzopyran-4-yl -H-formylglycine
and 216 wt.h. tetrahydrofuran, 4.2 parts by weight, was added portion wise. 50% dispersion of sodium hydride, followed by the addition of 16.5 wt.h. methyl ester-.
formic acid. Stirring is continued for one day at reflux (add several parts of methanol). The reaction mixture is evaporated. The residue is dissolved in a mixture of 1,1-oxy-bis-ethane and water. The aqueous phase is acidified with hydrochloric acid and extracted with dichloromethane. The organic layer is dried, filtered and evaporated. 68 parts by weight are added to the residue. 22.8 w / w methanol concentrated hydrochloric acid, 35 wt.h. water
g and 1-3.1 wt.h. potassium thiocyanate in 15 wt.h. water. The mixture is left at. stirring overnight at 60 ° C. The product is extracted with dichloromethane. The extract is dried (activated charcoal),
Q is filtered and evaporated. The residue is purified by column chromatography on silica gel using a mixture of trichloromethane and methanol (99: 1 by volume) as a mobile
5 phases. Pure fractions are collected and the eluent is evaporated. Get 28 wt.h. (88.3%) methyl- (cis + trans) -1-b-fluoro--2,3-dihydro-2-methyl-2- (1-methylethyl) -4H-1-benzopyran-4-yl - 2-mercapto H-imidazole-5-carboxylic acid in
as a residue (compound 1.58).
i
A mixture of 28 wt.h. methyl- (cis + trans) -1 -1-b-fluoro-2,3-dihydro-2-methyl-2- (1-methylethyl) -4H-1-benzopyran-45 -shH -2-mercapto-1 H- imidazole-5-kap-carboxylic acid, 75 wt.h. water, 30 wt.h. nitric acid and 0.1 wt.h. sodium nitrate is stirred for 2.5 hours at room temperature. Re-
Q stock mixture is poured into water and dichloromethane. The contents of the reaction vessel are made alkaline with sodium hydroxide solution in an ice bath. The mixture is filtered through diatomaceous earth and
5, the organic layer from the filtrate is dried, filtered and evaporated. The residue was purified by column chromatography on silica gel using a mixture of trichloromethane and methanol (99: 1 by volume) as eluent. Pure fractions are collected and the eluent is evaporated. The residue is further purified by column chromatography (high performance liquid chromatography) on silica.
55
gel using a mixture of methyl benzene and ethanol (in the ratio 97: 3 by volume) as eluent. Chis- The fractions are collected and the mobile phase is evaporated. The residue is converted to the salt of nitric acid in. 2-propane, 1,1-oxy-bis-ethane and 2,2-oxy-bis
-propane The salt is filtered off and dried in vacuo at 55 ° C. 14.4 parts by weight are obtained. (47.3%) methyl- (cis + trans) -1 - Јb-fluoro-2,3-dihydro-2-methyl-2- (1-methylethyl) -4H-1-ben zopyran-4-yl mononitrate -1 H-imidazole-5-carbonic acid, m.p. 124.6tfC (compound 1 .26),
Example 2. Methyl- (trans) -1- (2,3-dihydro-2-methyl-4H-1-benzopyran-4-yl) -1H-imidazole-5-carboxylic acid hemihydrate is also prepared, t. square 139 C (compound 1.73) and methyl- (cis) - (2,3-dihydro-2-methyl-4H-1-benzopyran-4-yl) -H-imidazole-5-carboxylic acid mononitrate, m.p. . 147.3 ° C (compound 1.76). These pure isomers are separated by separating a mixture of (trans) -Sh- (2,3-dihydro-2-methyl-4H-1-benzopyran-4-yl) glycine methyl ester and methyl- (cis) -P- ( 2,3-dihydro-2-me-TIL-4N-1-benzopyran-4-tl) glycine by silica gel column chromatography using a mixture of trichloromethane and methanol (in the ratio 99; 1 by volume) as the mobile phase and further purification of residues by column chromatography (high performance liquid chromatography) on silica gel using a mixture of dichloromethane and 2-propanol (in the ratio of 97.5; 2
as eluent and condensation of both isomers obtained by the method described in example 1
Example 3. 33.0 MAH. ammonium carbonate is added at room temperature to a solution of 19.3 wt.h. methyl 2- (2,3-dihydro-2 2, b-trimethyl-1-benzopyran-4-yl) formylamino-3-oxopropionic acid in 260 parts per hour. dimethylbenzene. The mixture is heated for 1 hour, then the temperature is raised to 120 ° C for 3 hours. Methyl-1- (2,3-dihydro-2,2,6-tri methyl-4H-1-benzopyran-4-yl) -1H- imidazole-5-carboxylic acid precipitates from solution, so pl. 100-101 ° C (compound 1.13).
Example 4. A mixture of 19.3 mah.h methyl-2-p2,3-dihydro-2, 2,6-trimeti-4H-1-benzopyran-4-yl) formylamino-3-oxopropionic acid, 65.0 May ammonium acetate and 100 parts of acetic acid are heated with a reverse

0
0
g
8 hours. Then an additional 50 mas is added. ammonium acetate and reflux continue for another 4 hours. The solution is diluted with 300 May "h. water and extracted twice 90 MAH. methyl benzene each time. The organic phases are combined, concentrated and separated by chromatography on silica gel. By concentrating the mobile phase, methyl 1- (2,3-dihydro-2,2,6-trimethyl 4H1-benzopyran-4-yl) -1H- -imidazole-5-carboxylic acid is obtained having a mp. 100-101 C (compound 1 about 1 3).
Example 5. A mixture consisting of 16 May. including 2-Q 2,3-dihydro-2, 2,6-trimethyl-4H1-benzopyran-4-yl) forylamine L-3-oxopropionic acid, 58 May, h. formamide and 12 math. hydrochloric acid, heated to 140 ° C in 8 hours. After cooling to room temperature, the reaction
"G
25 the mixture is extracted with a mixture consisting of
0
g
lot with t. pl
0
five
0
from May 100 waters and 70 may. including 1,1 - oxy-bis-ethane. The ether phase is separated and the aqueous phase is extracted twice with 70 m.h. 1,1-oxy-bis-ethane each time. The combined organic phases are dried over sodium sulfate and concentrated to dryness. The residue is crystallized and pure methyl 1- (2,3-dihydro-2.25 6-trimethyl-4H-1-benzopyran-4-yl) -1H-imidazole-5-carboxylic acid 100-101 ° C is obtained ( connection 1 .13).
Example 6. A solution containing 31 MAH. methyl 1- - (8-chloro-2,3-dihydro-4H-1-benzopyran-4-yl) -1Nimidazole-5-carboxylic acid mononitrate in 260 parts by weight, 60% nitric acid solution is stirred 45 min at room temperature (exothermic reaction). The reaction mixture is poured into crushed ice and the contents of the reactor are alkalinized. The product is extracted with trichloromethane. The insoluble product is filtered off (the trichloromethane layer is left) and dried. Methyl-1- (8-chloro-2,3-dihydro-6-nitro-4H-1-benzopyran-4-yl) -1H-imidazole-5-carbonose acid mononitrate is obtained. The trichloromethane layer obtained previously was washed with water, dried, filtered and evaporated. The residue is converted to a salt of nitric acid. The product is filtered, dried and get the second
91
fraction of 21 ma.h. (60.2%) Methyl 1- (8-chloro-2,3-dihydro-6-nitro-4H-1-benzopyran-4-yl) -1H-imidazole-5-carboxylic acid mononitrate.
Methyl-1- (8-chloro-2,3-dihydro-6-nitro-4H-1-benzopyran-4-yl) -1H-imidazole-5-carboxylic acid mononitrate mononitrate (compound 1.62) 28 ma.ch. (80.2%).
Example 7. A mixture consisting of 48 wt.h. methyl 1- (8-chloro-2,3-6-. -nitro-4H-1-benzopyran-4-yl) -1H-imidazole-5-carboxylic acid, 8 May, h. calcium oxide and 400 ma.ch. methanol, subjected to hydrogenation at room temperature and normal pressure in the presence of 2 May. 5% catalyst - palladium on coal. After uptake of the calculated amount of hydrogen, the catalyst is filtered off and the filtrate is evaporated. The residue is poured into trichloromethane. The organic layer is washed with water and evaporated. The residue is purified by column chromatography through silica gel using a mixture of trichloromethane and methyl (in a ratio of 90:10 by volume) as the mobile phase. Pure fractions are collected and the eluate is evaporated, the residue is converted to hydrochloride; the native salt in a mixture of 2-propanol and 2,2-hydroxy-bis-propane. The salt is filtered and left overnight to dry in vacuum at 80 ° C. Get 18.3 mah.h. (35.3%) 2-propanol monohydrochloride (1: 1) methyl-1 - (- 6-amino-2,3-dihydro-4H-1-benzopyran-4-yl) -1H-imidazole -5-carboxylic acid, TO pl. 146.0 C (compound 1 .135).
Example 8. To a stirred solution containing 2.8 May. H. methyl 1 - (b-amino-2,3-dihydro-4H-1-benzopyran-4-yl) 1H-imidazole-5-carbonic acid in 50 parts by weight. acetic acid, add 4 wt.h. acetic anhydride. The contents of the reaction vessel are left overnight with stirring at room temperature. After evaporation in vacuo, the residue is dissolved in trichloromethane. The resulting solution is washed with a 5% sodium hydroxide solution. The organic layer is evaporated, and the residue is converted to a salt of nitric acid in 2-propanone. The salt is filtered off and dried in vacuo to give 3.4 wt. Parts. (44.9%) mononitrate IU
7064810
tyl-1-Ј6- (acetylamino) -2,3-dihydro-4H-1-beneopyran-4-shG} -1 H-imidazol-5-carboxylic acid, so pl. 159.3 С
, (compound 1.136).
PRI me R 9. A mixture consisting
from 4.4 ma.ch. Methyl-1 - (6-amino-2,3-dihydro-4H-1-benzopyran-4-yl) -1H-imidazol-5-carbono) 0 monohydrochloride, acid, May 4. polyoxymethylene, 2 wt% h. potassium acetate, and 200 ma.ch. methanol, is subjected to hydrogenation at normal pressure and at 50 ° C with 2 mash. 10%
15 catalyst - palladium on coal.
After uptake of the calculated amount of hydrogen, the catalyst is filtered off and the filtrate is evaporated. The residue is dissolved in trichloromethane. The organic layer is washed with a solution of acid sodium carbonate and water,
dried, filtered and evaporated. The residue is converted to the hydrochloride salt in 2-propanol. The salt is filtered out, dried out in vacuum at 70 ° C and 3.3 m.ch. (73.4%) methyl 1- 6- (dimethylamino) -2,3-dihydro-4H-1-benzopyran-4-yl -1 -1-imidazole-5-carboxylic acid dichlorohydrate,
30 t. Pl. 136.5 ° C (compound 1.137). Example 10. To a stirred solution containing 6.0 May "h. Methyl-1- 3,4-dihydrospiro- (2H-1-benzopyran-2,1-cyclopentane) -4-cl -1H-imidazole-5-carboxylic acid mononitrate 135 mo.h about methanol, to - Bavl 3.2 mph. bromine. The mixture is stirred for 1 h at room temperature. The reaction mixture is poured.
4Q in water and the contents of the reaction co-, the vessels are alkalinized. The product is extracted with 1,11-oxy-bis-ethane. The extract is dried, filtered and evaporated. The residue is converted to a salt of nitric acid
45 in a mixture of 16 ma.h.
2-propanone and 40 ma.ch. 2,2-Oxy-α-bis-propane, Salt is filtered off, dried in vacuum and get 4,4 wt.h. (48.4%) methyl 1-1b-bromo50 mononitrate 3,4-dihydrospiro- (2P-1-benzopyran-2, 1-cyclopentane) -4 kg-1H-imidazole-5-carboxylic acid, t. square 162.3 ° C (compound 1.63).
Example 11. To solution, with ,,. holding 32 ma.h. methyl 1- (6-bromo-2, -3-dihydro-4H-1-benzopyran-4-yl) - j -1H-imidazole-5-carboxylic acid in 90 wt.h. , i-dimethylformamide, is added 8.6 wt.h. copper cyanide U). The contents of the reaction vessel were left overnight with stirring and refluxing. The reaction mixture is poured into 350 mAh., 10% sodium cyanide solution in the form and the whole is stirred for 1 hour at 60 ° C, the resulting product is extracted with methylbeneol, the extract is dried, the filter is collected, and the eluent is evaporated. Remain and evaporate. The residue is purified and the crystalline residue is crystallized from hexane. Semi-chromatography (high performance liquid chromatography) on silica gel using a mixture of hexane and acetic acid methyl ester (in the ratio 85:15 by volume) as the carrier. Pure fractions are collected and the eluent is evaporated. The residue is converted to a salt of nitric acid in 2-propanol and 2,2-oxy bis-propane. The salt is filtered off, dried and prepared on May 7th. (20S2%) methyl-1- (b-cyano-283 di-hydro-4H-1-benzopyran-4-yl) -1H-imidazole-5-carboxylic acid mononitrate, so pl. 169.6 ° C. (compound 1.147).
Example 12. A solution containing 80 wt.h. Methyl- -1- (2,3-dihydro-25 2-dimethyl-4H mononitrate) 1 The filtered product is filtered off and dried, and 2.36 parts by weight (63.5%) of ethyl-1 (2.3 dihydro-2 , 2-dimethyl-4H-5 -1-benzopyran-4-yl) -1H-imidazole-5-carboxylic acid, mp 80.9 C (compound -1138).
Example 14. 3.3 mach. 1-20 - (2,3-dihydro-2,2-dimethyl-4H-1-benzopyran-4-yl) -1H-imidazole-5-carboxylic acid is dissolved in 45 wt.h. heated 1 ", and dimethylformamide. After cooling to room temperature, 25 may be added. H. 1, l-carbonyl bis (1H-imidazole) and the contents of the reaction vessel are stirred .1 h at room temperature, then the contents are heated to ± 80 ° C and do35
-benzopyran-4-yl) -1H-imidazol-5-carbamide is a mixture consisting of 0.1 wt. h. side of the acid and 80 wt.h, 50% sodium hydroxide solution in 200 wt.h of water, stirred for 2 hours at reflux. After cooling, the reaction mixture is neutralized with acetic acid and the product is left to crystallize. The crystallized product is filtered off, washed twice with water and dried in vacuum at-80 ° C. Get 52 wt.h. (82%) 1- (2,3 dihydro-2,2-dimethyl-4H 1-benzopyran-4-yl) -imidazole-5-carboxylic acid, tG pl. 245.5 ° C (compound 1.132).
solution of sodium salt of cyclohexanol and 3 wt.h, cyclohexanol. After stirring for 5 days at i80 ° C, the mixture is evaporated. The residue is purified by column chromatography on silica gel using trichloromethane as the mobile phase. Pure fractions are collected and the eluent is evaporated. The residue is crystallized from. hexane. The resulting product is filtered and dried. 0.91 wt.h, (20.5%) of 1- - (2,3-dihydro-2,2-dimethyl-4H-1-benzopyran-4-yl) -1H-imidazol-5 cyclohexyl ester is obtained. -carbono Example 13. A solution containing 45 tons of t "pl- 128.1 ° C (connecting 3.3 parts by weight of 1- (2,3-dihydro-2,2-dimethyl-4H-1-benzopyranyl -4-yl) -1H-imidazole-5-carboxylic acid in 45 parts by weight of preheated K, AND-dimethylformamide, cooled to room temperature and then 2 parts by weight of 1.1 (carbonyl- bis-1H-imidazole. The contents of the reaction vessel are stirred at room temperature until the evolution of carbon dioxide stops (, 30 minutes). The mixture is heated to l dissolved 2.4 parts of ethanol and 0.1 parts of sodium ethoxide. Stirring was continued
ny 1139).
Example 15. A solution containing 4.2 wt.h. methyl trans-1- - (2,3-dihydro-2-methyl-4H-1-benzopide ran-4-yl) -1H-imidazole-5-carboxylic acid and 12 wt.h. iodomethane 65 wt.h. dichloromethane, stirred for 20 h at room temperature. The reaction mixture is evaporated, and the residue is recrystallized twice from 2, 2-hydroxy-bis-propane. The resulting product is filtered off, dried and trans-1- (2,3-dihydro-2 methyl-4H-1-benzopyran-4-yl) iodide is obtained. 55
They are kept for three days at. After evaporation, the residue is dissolved in water and trichlorometak. The organic layer is washed with water, dried, filtered and evaporated. The residue is purified by column chromatography on silica gel using trichloromethane as the mobile phase. Pure fractions
The resulting product is filtered off and dried, and 2.36 parts by weight are obtained. (63.5%) ethyl-1 (2,3 dihydro-2,2-dimethyl-4H-1-benzopyran-4-yl) -1H-imidazol-5-carboxylic acid, so pl. 80.9 ° C (compound 1 .138).
Example 14. 3.3 mach. 1- - (2,3-dihydro-2,2-dimethyl-4H-1-benzopyran-4-yl) -1H-imidazole-5-carboxylic acid is dissolved in 45 wt.h. heated 1 ", and dimethylformamide. After cooling to room temperature, is added on 2 May. H. 1, l-carbonyl bis (1H-imidazole) and the contents of the reaction vessel are stirred .1 h at room temperature, then the contents are heated to ± 80 ° C and up to 5
0 Add a mixture consisting of 0.1 mash.
solution of sodium salt of cyclohexanol and 3 wt.h, cyclohexanol. After stirring for 5 days at i80 ° C, the mixture is evaporated. The residue is purified by column chromatography on silica gel using trichloromethane as the mobile phase. Pure fractions are collected and the eluent is evaporated. The residue is crystallized from. hexane. The resulting product is filtered and dried. 0.91 wt.h, (20.5%) of 1- - (2,3-dihydro-2,2-dimethyl-4H-1-benzopyran-4-yl) -1H-imidazol-5 cyclohexyl ester is obtained. -carboxylic acid t "PL- 128.1 ° C (compound 1 .139).
Example 15. A solution containing 4.2 wt.h. methyl trans-1- - (2,3-dihydro-2-methyl-4H-1-benzopiran-4-yl) -1H-imidazole-5-carboxylic acid and 12 wt.h. iodomethane 65 wt.h. dichloromethane, stirred for 20 h at room temperature. The reaction mixture is evaporated, and the residue is recrystallized twice from 2, 2-hydroxy-bis-propane. The product obtained is filtered off and dried and trans-1- (2,3-dihydro-2 methyl-4H-1-benzopyran-4-yl) iodide is obtained.
-5- (methoxycarbonyl) -3-methyl-1H-imidazolium (compound 7.04).
Example 16. For a solution of 5.4 mAh stirred and cooled to 0 ° C. methyl trans-1- (2,3-dihydro-2-methyl-4H-1-benzopyran-4-yl) -1H-imidazole-5-carboxylic acid in 130 parts by weight. dichloromethane. add 3.4 wt.h. 3-chlorobenzene dicarboxylic acid. After stirring for 24 hours at room temperature, the reaction mixture is washed until 100 May. an aqueous solution of sodium hydrogen carbonate (0.03 M) and water, dried, filtered, evaporated at a temperature below 30 ° C. The residue is purified by column chromatography on silica gel using a mixture of trichloromethane and methanol saturated with ammonia (in the ratio 95: 5 by volume) as the mobile phase. Pure fractions are collected and the eluent is evaporated. The residue is crystallized from hexane. The product is filtered off and dried to give N-oxide methyl trans-1- (2,3-dihydro 2-methyl-4H-1-benzopyran-4- -yl) -1H-imidazole-5-carboxylic acid (compound 7.101) .
All other compounds and intermediates shown in Table. 1 - 8, can be obtained by similar methods of synthesis.
Example 17. Herbicidal action in the pre-emergence period.
In the greenhouse, directly after sowing the test plants into seed beds, the soil surface is treated with an aqueous dispersion of the test compounds obtained from a 25% emulsifiable concentrate or from a 25% wettable powder with test compounds that due to their insufficient solubility could not be prepared as emulsifying concentrates. Two different series of concentrations are used, corresponding to 1 and 0.5 kg of the test compound per hectare, respectively. Sowing baths are kept in a greenhouse at 22-25 ° C and 50-70% relative humidity. Experimental results are evaluated after three weeks on the following scale: - plant did not ascend or completely; 2-3 - very strong effect; 4-6 - moderate action; 7-8 - light action; 9 - no action was observed.
7064814
In this experiment, the test compounds of formula (l) are most effective against monocotyledonous grass weeds, while cultivated plants, such as maize, are not harmed or given only minor damages at these doses.
.Q results (pre-emergence experiment) are given in Table. 9.
Example 18. Herbicidal action in the post-emergence period (contact herbicide).
.g A large number of weeds and cultivated plants are sprayed in the period after the emergence of seedlings in the 4-6th leaf stage with an aqueous dispersion of the active ingredient in quantities of 4 and 2 kg / ha
20 at 24-26 ° С and relative humidity of 45-60%. The results of the experiment are evaluated at least 15 days after the treatment according to the same scale that is used in evaluating the results of the treatment before germination. In this experiment, the compounds of formula (l) are also more effective against weeds. Cultivated plants (corn and rice)
3Q is either not damaged at all or is damaged only at higher concentrations of the test compound.
The results of post-harvest processing are shown in Table 10.
Example 19. Herbicidal action in transplanted rice crops.
40 25-day old shoots of Yamatiino variety rice are transplanted into large plastic containers. Weed seeds are sown in these containers, namely, cinnamon, seirpus, mono45 choria and arrowhead. The containers are filled with water to such a level that a 2.5 cm thick layer of water covers the surface. After three days in the greenhouse conditions, dilute aqueous dispersions of the active compounds are added to a layer of water in doses of 2000, 1000, 500, 125 and 60 g of the active ingredient per hectare. Containers kept in the greenhouse for four
55 weeks at 25 ° C and high humidity. The evaluation of the experiments was carried out on the damage scale presented in Example 17.
The results are summarized in table. P. .
15
Pre-emergence herbicidal activity.
In the greenhouse, the seeds of the test plants are sown in plastic pots filled with sandy soil which is then covered with a layer of 0.5 cm of the same soil. Test compounds are dissolved in acetone (100 mg of compound in 4 ml of acetone) and then diluted with tap water immediately before use. Each pot receives 20 ml of the test solution, which is evenly distributed over the soil surface using a plastic syringe. Dilution of the test solution is carried out in such a way that the amount of active ingredient per pot corresponds to 4 kg / ha.
Test plants are listed in Table 12 and 13.
During the entire test period (4 weeks), the pots are kept on the shelves under normal greenhouse conditions. Temperature and humidity vary according to the time of day and season.
Herbicidal activity is assessed on a scale of plant growth, following a semi-log scale: 1 - no effect (growth comparable to untreated plants); 2 - 4.5% effect; 3-5% effect; 4-10% effect; 5-15% effect; 6 - 25% effect; 7 - 35% effect; 7-8-50% effect; 8 - 6795 effect; 9 - 100% effect (complete destruction of plants),
A score of 8.9 (tsbl, 12) indicates that the herbicidal activity is about 85%, whereas
(8) 9
nosti closer to 9 than to 8, and
closer to 8 than to 9.
indicates that the active is indicated8 (9)

权利要求:
Claims (1)
[1]
Invention Formula
The method of obtaining the 1-heterocyclyl-1H-imidazole-5-carboxylic acid derivative of general formula I
NRJO-COOR,
to&
70648tb
where R is hydrogen or mercapto group;
R2 is hydrogen, C-C-y-alkynyl,
C 1 -Ct-cycloalkyl, coxy, C-C-alkyl or aryl-C-C-alkyl;
p O, 1 or 2;
Y is the group CH2-S (o) m-CH1-0-, CHg-M (E) or -CH-N-, where a heteroatom is attached to the carbon atom of the benzene ring and m O, 1 or 2, E is hydrogen, C-C-alkyl, C-Cg-alkanoyl or 4-methylphenylsulfonyl;
Yu
15
five
0
five
0
R, R, Rg. and R6 each independently
hydrogen, Cj-Cg-alkyl, mono-i or di- (aryl) -C4-C5-alkyl, C -Cfe-alkoxy, halogen, Cz-C7-alkenyl, aryl, -alkyl, substituted by 1-3 halogen atoms, (C "-C-alkoxyl, substituted with 1 to 3 halogen atoms, or R e and R taken together may form a condensed benzene residue, which may optionally be substituted with 1 or 2 substituents, each of which is independently selected among hydrogen , C-C-alkyl, C (-C5-alkoxy, halogen, C, -C-alkyl, substituted by 1–3 halogen atoms, C – Cg – alkoxy, substituted by 1 –3 halogen atoms, nitro groups , amino groups and NH-CO-Q, or R j and Rq, are Heminally substituted, they will be able to form a spirotschklichesky carbon ring 7
with, with
S
0
five
- each independently hydrogen, C, -C5-alkyl, C, -C5-alkoxy, halogen, C, -C3-alkyl, substituted with 1–3 halogen atoms, C, –C5-alkoxy, substituted with 1–3 halogen atoms, cyano a group, a nitro group, an amino group, a mono- or di-Cc-C-alkylamino or NH -CO-Q, where Q is a C -Cy-alkyl and aryl is phenyl, optionally substituted by 1-3 substituents, each of which are independently chosen among C (-C5 alkyl, C-CЈ-alkoxy and halogen,
17
moreover, RjjR, R5 and R & have the indicated values,
may be substituted on any carbon atom to form a Y-containing part of the bicyclic ring system including GHz. or CH-group, or - (CHg.) coal or -CH2S-, -CHNO -, CH2N (E) - or -CH--N-fragments,
its salt or stereochemically isomeric form, characterized in that compounds of the general formula II are condensed
ABOUT
ns-and-shg-so (Zhg
Ш5
iCHito
where, n and Y are specified
values with -alkyl ester of formic acid,
in the presence of a base in an inert reaction solvent, and the resulting intermediate of general formula III is treated
Rl
P
ABOUT
AND
l (SVDp
where, n and Y are specified
value;
Z is an alkali metal atom
alkali metal isothiocyanate in the presence of an acid, the 2-mercapto-imidazole compound of formula 1a thus obtained
Jsi
fyOOC-0-SH
7064J13
where RЈ-RЈ and HM6101 are the specified values,
isolate or interact. sodium nitrate in the presence of nitric acid in an aqueous medium with the release of the target product, where RJ is hydrogen, or by transferring the target product, where R is hydrogen, or a mercapto group, salt by treatment with acid or base, or by isolating the target product in the form its stereochemically isomeric form.
five
Priority featured:
02.27.86 with R7 and R - each independently hydrogen, C (-Se-alkyl, -alkoxy, halogen, trifluoromethoxy,
0 difluoromethoxy, nitro, amino or
-NH-CO-G, where G is C, -Sb alkyl; Rg and R4 are each independently hydrogen, C-C6-alkyl, Cf-C6-alkoxy, halogen, trifluoromethyl, difluoromethoxy, nitro,
5 amino, phenyl or —NH — CO — G; where G is C-Cg-alkyl or R and R, j. together form a condensed benzene core or a spirocyclic carbon ring with 3-7 carbon atoms.
QEg is hydrogen, C1-C7-alkyd, C-C7-alkenyl, C-C7 alkynyl or -cycloalkyl; n - O, 1 or 2, Y group, -CH4-0, -СНг-КЕ
or, where a heteroatom is attached to a carbon atom of the benzene ring, E is hydrogen, C-Cg-alkyl or C -C y-alkanoyl;
12/19/86 with R4-C ,, - St-alkoxy,
C, -C7-alkyl or aryl-C-C5-alkyl; Y is the group —СНг-5 (о) t, t is 0 or 2,
-CHi-N- E
where E is 4-methylphenylsulfonyl; R-j, R, j. , R5, R6 are each independently hydrogen, C-Cg-alkyl, mono- or di- (aryl) C-Cg-alkyl, C (-C-alkoxy-halo, C3-C7-alkenyl, aryl-C1-C5- -alkyl substituted with 1-3 halogen atoms, C, -C-alkoxy substituted with 1-3 halogen atoms; R and R4 together form a condensed benzene residue, which can be substituted with one or two substituents, each of which is independently selected from hydrogen, C-C5 alkyl, C-C5 alcock
nineteen
C-halide, C-Su-alkyl, substituted with 1 to 3 halogen atoms; With C-C-alkoxy, substituted with 1 to 3 halogen atoms, nitro, amino and -NH-CO-G or R 5 and RH are geminal substituted, they can form a spirocyclic carbon ring with 3–7 carbon atoms R7 and Eg each, independently 57064820
-alkyloxy, halo, C ,, -C-a-alkyl, substituted by one or three atoms of halogen, cyano, nitro, amino, mono-di-C-Su-alkylamino- or -NH-CO-G,
5 G — C — C-alkyl and aryl-phenyl substituted with one or three substituents, each independently selected from — alkyl, C — C-alkoxy or halo,
N
AJUooR,
N
1,2253
H
sn „o
table 2
Table 3
H
H
M.p. 186.3 С
25
NI
RljgLcooR2
26 Table 4
Table 5
N.
RiAjLcOOR2
N
27
1570648
N.
Rj-o-coor
4.0 4.02 4.05
H
sn, n
T. pl. 87.5-89 ° C -o.
NN N
SH CH, HHH-H T. pl. 194-195 С
Н СН1 2-ШЦ 2-СН3 Н Н HNO (t. Pl. 66.1 ° С)
5.03 5.04 5.15
5.16
H
SH
n n
CH3
ch3
CH3
NNN NT, pl. 131-132 ° C
HHH H. T. pl. 209 ° C (decomp.)
H NN N .NNO (m. Pl. 163.5 ° C,
different)
HHH H. T. pl. 202 ° C (decomp.)
ons / cng-soo g "G
8.01 1 CH3 HHHH-0-CHЈ-T. square A5-118 ° C.
8.06I CH3 HH8-C1 H -0-CHE-T. square 103.4 ° C
8.12 CH, 2-C, Hr-2-CHD HH-0-CH, - T. square 109.6 ° C
28 Table 6
T. pl. 87.5-89 ° C -o.
T. pl. 194-195 С
Table 7
Table 8
Corn
Alopecurus myos
Rosichka (digitaria sang
"Peasant's Ezhovnik
Brisket prickly Schyritsa colossus Chenopodium sp. Chrysanthemum is barren Galium aparine Violet tricolor Veronica tim nolistna Solanum nigrum
Table 9
31
Jamabino Variety Rice Seirpus
Monochoria Arrowhead
Jamafcino Rice
The yearbook
Seirpus
Monochoria
Arrowhead
l
Rice varieties Jamabino Ezhovnik
Connection1.104
567899
111111
111112
111112
444566
Connection1 „05
999999
111133
111113
111113
444689
Compound1 .08
889999
111112
Table 10
Table and
Known compound: N y coax
Table 12
sn
CH3
The proposed connection j
at coaxial
NN
2- (CHt) 5-2 2- (SNHHG-2 NN
6-Vg H 7-CH,
6-CN
2-CH-, 2-C, -HT-i 6-F
Editor N. Gunko
Compiled by G. Zhukov
Tehred L. Serdgokova - Corrector. Shekmar
Order 1461
Circulation 324
VNIIPI State Committee for Inventions and Discoveries at the State Committee on Science and Technology of the USSR 113035, Moscow, Zh-35, Raushsk nab 4/5
Table 13
9 9 8
(8) 9 9
8.9 9
8.9 9 9
Subscription

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引用文献:

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US3485917A|1966-04-14|1969-12-23|Janssen Pharmaceutica Nv|Composition and method for combating fungus with imidazole carboxylates|

DE2053080C3|1970-10-29|1979-08-23|Bayer Ag|N-substituted imidazoles and their use as drugs|

US4659730A|1984-06-18|1987-04-21|Eli Lilly And Company|Aromatase inhibiting imidazole derivatives|

GB8516573D0|1985-07-01|1985-08-07|Janssen Pharmaceuticaa Nv|Controlling weeds|GB8612796D0|1986-05-27|1986-07-02|Fbc Ltd|Fungicides|

GB8630759D0|1986-12-23|1987-02-04|Janssen Pharmaceutica Nv|Carboxylic acid derivatives|

GB8631091D0|1986-12-31|1987-02-04|Janssen Pharmaceutica Nv|1-cyclyl/polycyclyl substituted-1h-imidazone-5-carboxylic acids|

US4878940A|1987-04-02|1989-11-07|Janssen Pharmaceutica N.V.|Herbicidal 1,5-substituted 1H-imidazoles|

EP0305330A1|1987-08-25|1989-03-01|Ciba-Geigy Ag|Imidazole derivatives|

EP0305332A3|1987-08-26|1990-04-04|Ciba-Geigy Ag|Imidazole derivative|

EP0314852B1|1987-11-06|1993-11-18|Ciba-Geigy Ag|Process for the preparation of 1-substituted imidazole-carbonic acid and derivatives|

GB8812765D0|1988-05-28|1988-06-29|Beecham Group Plc|Novel compounds|

US4992090A|1988-06-13|1991-02-12|Ciba-Geigy Corporation|Herbicidally active 5,6-dihydrocyclopentathiophenyl-imidazole derivatives|

IL91542D0|1988-10-06|1990-04-29|Erba Carlo Spa|N-imidazolyl-and n-imidazolyl-methyl derivatives of substituted bicyclic compounds,their preparation and pharmaceutical compositions containing them|

CA2648831A1|2006-05-05|2007-11-15|Ulrich Reiser|Spiro-benzopyran-2, 4' -piperidine-and cyclohexane derivatives as inhibitors of specific cell cycle enzymes|

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法律状态:

优先权:

申请号 | 申请日 | 专利标题

US83362386A| true| 1986-02-27|1986-02-27|

US94428486A| true| 1986-12-19|1986-12-19|

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