• 专利附录
  • 专利说明
  • 权利要求
  • 类似技术
  • 同族专利
  • 引用文献
  • 法律状态
  • 优先权
    • 专利摘要:
    Benzimidazole derivatives of the formula <IMAGE> in which R is an alkyl group having 1 to 6 carbon atoms, an alkenyl group having 3 to 5 carbon atoms, an alkynyl group having 3 to 5 carbon atoms or a benzyl group, which is unsubstituted or monosubstituted to disubstituted by a methyl group, halogen or a nitro group; R1 is hydrogen, an alkanoyl group having 1 to 4 carbon atoms, an alkoxycarbonyl group having 1 to 4 carbon atoms, a N,N-dialkylcarbamoyl group or N,N-dialkylthiocarbamoyl group, each having 1 to 4 carbon atoms in the alkyl groups, an alkylsulphonyl group having 1 to 4 carbon atoms, a benzoyl group, a phenylsulphonyl group, a 4-methylphenylsulphonyl group or the radical, <IMAGE> in which Q is a carbonyl group, a thiocarbonyl group or an oxalyl group; R2 is hydrogen, halogen or a methyl group; R3 is hydrogen, halogen, a methyl group or an alkoxy group having 1 to 4 carbon atoms; R4 is hydrogen, halogen or a methyl group; X is oxygen or sulphur; Y is halogen, an alkyl group having 1 to 4 carbon atoms, an alkoxy group having 1 to 4 carbon atoms, a methylthio group, a methylsulphinyl group, a methylsulphonyl group, a trifluoromethyl group, a nitro group, a hydroxyl group, a cyano group or an alkanoyl group having 1 to 4 carbon atoms in the alkyl moiety m is 0, 1, 2 or 3; and n is 0, 1 or 2. Included are, if R1 is not hydrogen, the tautomeric compounds of the formula I. The compounds are effective for combating helminths in domestic and useful animals.
    公开号:SU1097196A3
    申请号:SU782601448
    申请日:1978-04-11
    公开日:1984-06-07
    发明作者:Жак Галлей Жан；Кюне Манфред；Мейер Альфред；Рехштайнер Освальд；Шелленбаум Макс
    申请人:Циба-Гейги Аг (Фирма)；
    IPC主号:
    专利说明:

    I. The invention relates to a process for the preparation of new benzimidazole derivatives of the formula where R is (-alkyl, C is Su-alkynyl, C-C, alkenyl or, if necessary, once substituted by methyl, halo gene, or benzyl nitro group; hydrogen, halogen or methyl; hydrogen, halogen, methyl, C — C-alkoxy; hydrogen, halogen or methyl; oxygen or sulfur; halogen, C — C4 alkyl, methyl thio, methylsulfinyl, methylsulfonyl, trifluoromethyl, hydroxyl, cyano or alkanoyl with 1-4 carbon atoms in the alkyl part, methoxy; tn 0-3-, n 0-2, possessing anthelmintic activity A known method for the preparation of sulfur-containing derivatives of bezimidazole, the fynthesis of benzimidazolylthiones with halo derivatives, followed by oxidation of the resulting product, for example, peracid, the purpose of the invention is the synthesis of new compounds possessing valuable properties. concluding that the compound of the general formula I "3v-. (Ii) reacting with, R, -sulfuryl or R-tosylate, where., Y and nt have the indicated values, at 0-100 o, in water, an organic solvent or in their mixture in the presence of a base to isolate the target product or with subsequent oxidation of the obtained product with (-20) - in water or organic acid in the presence of KMPO 96 peracid or H „0 and isolation of the target product. Advantageously, an organic base is used as a solvent. Example 1. Preparation of 5-chloro- / 2, A-dichlorophenrxy / -2-methylthiobenzimidazole. To a solution of 400 g of 5-chloro-6- / 2, 4 dichlorophenoxy / -2N-1, 3-dihydro-benzimidazole-2-thione and 175 g of potassium hydroxide in a mixture of 175 ml of water and 350 ml of ethanol dropwise within 30 minutes 73 ml of methyl iodide are added, and the temperature is maintained at tO15 C by cooling. For complete conversion, the reaction mixture is first kept stirring for 30 minutes at room temperature, then for 1 hour at and again at room temperature for 18 hours. The resulting emulsion is poured in a thin stream of 5 liters of water for 30 minutes, a colorless precipitate is formed, which is filtered off, washed with 3 liters of water and dried under vacuum. Obtain 400 g of 5-HLOR-6- / 2, 4-dichloro-phenoxy / -2-methylthio-benzimidisol with so pl. 178C, which corresponds to a yield of 98%. Purified by recrystallization from a mixture of alcohol and water, the product melts at 185-186 ° C. Example 2. Preparation of 5-chloro- / 2, 4-dichlorophenoxy / -2-methyl-sulfinyl-benzimidazole. Chilled to a solution of 35 g of 5-ChLOR-6- / 2, 4-dichlorophenoxy / 2-methylthio-benzimidazole in 1750 ml of chloroform over 30 minutes with stirring, drop a solution of 19.5 g of 90% m-chloroperbenzoic acid in 450 ml of chloroform. The mixture is kept stirring for 3 hours at room temperature, then at room temperature for 15 hours and then freed from a small amount of precipitate. The filtrate, which still contains residual m-chloroperbenzoic acid, is treated with sodium bisulfite solution, washed with water, dried over calcium chloride, filtered and concentrated in vacuo. After recrystallization of the residue from 500 ml of ethyl acetate with simultaneous clarification of the hot solution with active carbon and subsequent drying of white crystals, 26 g of 5-chloro 1097 6- / 2, A-dichlorophenoxy / -2-methylsulfinyl-benimidazole with mp. 206-208 C, which corresponds to a yield of 69%, Example 3. Preparation of 5-chloro 6- / 2, A - dichlorophenoxy / -2-methyl-. sulfonylbenzimidazole. Supported by cooling at room temperature a solution of 100 g of 5-chloro-6- / 2, 4-dichlorophenoxy / -2-methylthiobenzimidazole in 800 ml of glacial acetic acid for 30 min with stirring, 122.5 ml of 40% - peracetic acid. The resulting dark red solution is stirred for an additional 15 hours jj at room temperature. A thick suspension is formed, which is mixed with 4 liters of demineralized water. Then the precipitate formed is filtered off with suction, washed with water and dried in a vacuum at 50 ° C. 96 g of 5-chloro-6/2, 4-dichlorophenoxy / -2-methylsulfonylbenzimidazole are obtained. 215-218 C, which corresponds to a yield of 89%. Analogously to the methods described in examples 1-3, the following compounds are obtained "xL 204-206 215-218
    Table 1 189-294 191-193 197-200 39-243 66-170 5-187
    C1
    179-180
    Continued table. one
    .... .. „-.
    C1
    169-170
    C1
    172-173
    C1
    C1
    127-129
    196-197
    8 C1
    175-176
    CH.
    191-193
    C1
    ten
    eleven
    CH,
    203-204
    198-199
    C1
    12
    13
    CH,
    14
    C1
    15
    CH,
    SN CHZ
    184-186 V
    171-173
    0 (jl
    209-211
    CH: (JIHTVO184-186
    23
    Cl
    24
    H
    25
    H
    26
    AND
    27
    28
    n
    29
    155-157
    155-156
    211-212
    131-134
    152-154
    172-174
    177-178
    35
    H
    105-106
    H
    36
    H
    37
    157-159
    190-192
    H
    38
    H
    39
    191-192
    AND
    40
    118-121
    H
    41
    137-139
    042
    H
    S1TSO43
    44
    H
    192-194
    165-168
    163-165
    C1
    45
    46
    H
    47
    W
    48
    CjHjO51
    nC HgO52
    Br
    53
    nC HgO210-214
    169-170
    90-92
    68-72
    78-80
    128-130
    105-108
    165-167
    93-95
    Structural formula
    Compounds
    I
    Melting point at С
    93-95
    112-115 Table 3 1-CH2 CH CH2. 147-150 2, 122-125 10971 5 to 15 20 6 White laboratory rats infest liver flukes (Fasciola hepatica). After the flow of the patent period, three consecutive days every day are treated once a day for the experience of 3 affected rats with a corresponding biologically active substance, which is administered in the form of a suspension through a stomach tube. Biologically active substances are tested in doses of 300, 100, 30 and 10 mg / kg body weight. Two weeks later after administration of the biologically active substance, the experimental animals are sacrificed and opened. The evaluation is carried out after opening the experimental animals by comparing the number of parasites remaining in the bile ducts with the untreated. Continuation of the table. 5 1097196 16 Continuation of the table. five
    权利要求:
    Claims (2)
    [1]
    1. Process for the preparation of benzimidazole derivatives of general formula wherein R ^ - C1 ~ s alkyl, Cj-Cj-alkynyl, Cj-Cy-alkenyl or optionally mono- disubstituted by methyl, halogen nitro or benzyl;
    R-, - hydrogen, halogen or methyl;
    Rj is hydrogen, halogen, methyl, C 1 -C 4 alkoxy;
    R + is hydrogen, halogen or methyl;
    X is oxygen or sulfur;
    Y is halogen, C ^ -C ^ alkyl, methylthio, methylsulfinyl, methylsulfonyl, trifluoromethyl, hydroxyl, cyano or alkanoyl with 1-4 carbon atoms in the alkyl part, methoxy;
    t is 0-3; η = 0-2, characterized in that the compound of the general formula is reacted with R ^ = gal, R 4 -sulfoester or R ^ -tosylate, where R n ~ R 4 , Y and hl have the indicated meanings, at 0- 100 ° C in water, an organic solvent, or a mixture thereof in the presence of a base with the isolation of the target product or with subsequent oxidation of the resulting product at (-20) - 100 ° C in water or an organic acid in the presence of KMnO ^, peracid or Η ^ θ2 and b 1G of the target product.
    [2]
    2. The method of pop. 1, characterized in that in the quality of the solvent using an organic base.
    SU, „, 1097196
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    同族专利:
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    法律状态:
    优先权:
    申请号 | 申请日 | 专利标题
    LU77120A|LU77120A1|1977-04-12|1977-04-12|
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