• 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:
    A process for the preparation of a compound of the formula: <IMAGE> wherein R1 is alkyl, alkyl substituted by halogen, alkyl substituted by alkoxy, aryl, aryl substituted by halogen, aryl substituted by alkyl, aryl substituted by alkoxy, aralkyl, aralkyl substituted by alkoxy, cycloalkyl, cycloalkyl substituted by halogen, cycloalkyl substituted by alkyl or cycloalkyl substituted by alkoxy, and R2 is an aromatic group, an aromatic group substituted by alkyl, an aromatic group substituted by halogen, an aromatic group substituted by alkoxy, a heteroaromatic group, a heteroaromatic group substituted by alkyl, a heteroaromatic group substituted by halogen, or a heteroaromatic group substituted by alkoxy, by the reaction of phosgene with a phenol of the formula:
    公开号:SU906372A3
    申请号:SU772479558
    申请日:1977-05-12
    公开日:1982-02-15
    发明作者:Тот Геза；Тот Иштван；Монтай Тибор
    申请人:Хиноин Дьедьсер Еш Ведьесети Термекек Дьяра Рт (Инопредприятие)；
    IPC主号:
    专利说明:

    The invention relates to an improved process for the preparation of urea compounds of the general formula O: R i Ej-NH-lli-UC, where R is alkyl, hydrogen; C-methyl, methoxy, - or R. and Rfl together form a d - B group, where RA is a carbalkoxy amino group, or R and R (j together form a group, where the thiazole ring can be replaced by a halogen atom; alkyl, cyclohexyl, feHMji, which may be substituted by one or two halogen atoms which are important in very wide areas of organic chemistry as medicines, for example, derivatives of 1-phenyl-2-butyl sulfonamido urea, used as medicines for the treatment of humans. Derivative Method urea of general formula T by reacting carbamates with isocyanate in an organic solvent at a temperature of from room temperature to 100 ° C. A disadvantage of this method is the use of isocyanates, which are obtained by reacting a primary amine with phosgene, after which the carbamoyl chloride is formed by treating hydrochloric acid, isocyanate. In addition, the yield of the target product is significantly reduced due to the fact that the intermediate isocyanate can be obtained with a yield of no more than 60-70. The aim of the invention is to simplify the method. The goal is achieved by the fact that the amine of the general formula. NH where R / and Ri have the indicated meanings and the amine of the general formula Rj-NHj, III where R has the indicated meanings, is reacted 4 with phosgene at 20-110 ° C in an environment of halogenated hydrocarbons in the presence of acid binding agents. Preferably, an alkali metal carbonate is used as an acid binding agent. The components involved in the reaction, i.e., two different amines, are added along with phosgene to the reaction mixture containing the solvent. For carrying out the process, it is essential that an acid binding agent be added to the reaction mixture at the appropriate moment, and it can be added from the very beginning of the reaction or at a subsequent stage. Alkali metal hydroxides, alkali metal carbonates or alkaline earth metal carbonates can be added as an acid binding agent, and they are added to the mixture continuously. The addition is preferably carried out in such a way that the acid binding agent forms a heterogeneous phase precipitating from the organic reaction mixture. The same organic bases or ammonium carbonate are suitable as an acid binding agent. The acid binding agent can be used in solid form or as a solution (for example, an aqueous solution), preferably halogenated hydrocarbons (for example, dichloro ethane or dichlorobenzene) can be used as a solvent. Water-immiscible solvents (e.g., toluene) are also suitable for this purpose. Example 1. To 200 ml of dichloromethane, add 19.1 g of 2-carbomethoxyamine-benzimidazole and 10 g of n-butylamine to 200 ml of phosgene, followed by stirring at 20-22 ° C for 1.5 hours. Then, 21 g of potassium carbonate is added in parallel with the introduction of phosgene over C min. After the reaction was quenched, the reaction mixture was stirred at 25-30 ° C for 3 hours, left to stand overnight, cooled, filtered, washed with water and acetone. 22.0 g of 1-butylcarbamoyl-2-carbomethoxyamino-benzimidazole (75.9-0) are obtained, 1 ppm 320 ° C. Example 2. A flask equipped with a stirrer, a gaseous feed tube and an addition funnel was charged with 30 g of concentrated hydrochloric acid, after which 22 g (0.30 mol of butylamine (30%)) was added with cooling and stirring. is set at a neutral level. To the solution are added 100 ml of ortho-dichlorobenzene from the reaction mixture under reduced pressure (100-150 mm Hg) and 19-20 ml of water are distilled off. The residue is cooled to 25-30 0. The apparatus is added 2 g of diethylamine are fed, and nitrogen is fed there for 2 h at 70 ° C, after which the reaction mixture After cooling to room temperature, 2.8 g (0.2 mol) of N-acetylpara-aminobenzenesulfonamide are added to a mixture of 100 ml of water, 15 g of sodium hydroxide and 20 ml of ortho-dichlorobenzene, and then reaction mixture. Within 30 minutes, 8 g of phosgene are introduced, then phosgene is fed into the apparatus at 100-110 ° C for 2 M at the indicated tempo. The reaction mixture is stirred for 3 hours at room temperature, then 200 ml of water are added to the mixture . The mixture was adjusted to pH 8.5 with concentrated hydrochloric acid with concentrated hydrochloric acid and stirred at this temperature for 2 hours and filtered. 7 g of N-acetyl-para-aminobenzenesulfonamide are recovered. . The aqueous dichlorobenzene mixture is separated, 8 g of sodium hydroxide solution is added to the aqueous phase and stirred at 90 ° C for
    1.5 hours. After cooling, the mixture is adjusted to pH 5 with dilute hydrochloric acid. After 3 hours of stirring, the precipitated product is filtered and. washed with water. A.0.1 g of N- -para-aminobenzenesulfonamido-N is obtained - util-urea (88.6), t.n. 143-1 h C.
    Example 3. To 150 ml of chlorobenzene were added 1.1 g of 2-methoxy-carbonyl-amyl-benzimidazole, then 12 g of cyclohexylamine and ammonium carbonate were added to the reaction mass for 1 hour in parallel with the supply of phosgene. Phosgene is introduced into the system further over the next 4aLa, and the mass is stirred for 2 hours at. , and at the same time nitrogen gas is introduced into the system. After cooling, the chlorobenzene phase is diluted with dichloromethane, washed with water, evaporated and the crystalline precipitate washed with water and then with acetone.
    Yield 1 cyclohexylcarbamoyl-2-methoxm-caobonylamino-benzimidazole 23.9 g (77, b.
    Example 4. Proceed as in Example 1, however, 19.1 g of 2-methoxycarbonyl-amino-benzimidazole are introduced into the reaction with g of p-chlorophenyl-aniline in the presence of 10 g of triethylamine. In this case, 1-p-methoxycarbamoylamino-benzimidazole is obtained with a yield of 89.1.
    Example 5- Proceed as in Example 1, however, 20.5 g of 2-ethoxycarbonyl-amino-benzimidazole are introduced into the reaction with 10 g of aniline in the presence of 20 g of calcium carbonate. You get 1 phenylcarbamoyl. L-2-. - ethoxycarbonyl-amino-benzimidazole with the release of 71, 7%.
    Similarly to the above, the compounds listed in the table are obtained.
    p-SdNd
    75.9
    J5H- C-
    about
    CHj
    OdH.3 305-3076i
    n-C.H
    92.6
    307-3 0
    I :: J ::: I: L: I
    Table continuation
    ::: :: i: i ::
    to;
    Н- С- 326-32889,1
    one
    di
    -h
    IN YOINS 30-331 92.1 b
    10CHjk
    d -
    NH- -OdgHs 27 + -27555.9
    Pn-C Hg
    litZ-l
    12
    CIJ.H5H
    di
    13
    SNa-CHdi
    14
    sn
    3-SNDO
    15 -SaN
    K- d
    128-130
    n- d-odgHs 323-32if
    71.2 o
    i :: i :::: i :: ii
    16-cdnd
    17 N
    :: i ::: i:
    Nb-OdjHs 305-30779.1
    ABOUT
     d in- b-OdgHs 323-32475,6
    about
    18
    H C-OdgHs 326-32771,7
    about
    nineteen
    to-
    H- d-OdgKs 321-32381.8
    20
    be.
    tl
    21
    ".No
    Y I and 288-29069,7
    g
    22
    23-CdNd
    216-218 89.7
    权利要求:
    Claims (2)
    [1]
    i 11 Thus, the proposed comp allows to obtain target products in one stage. The invention The method for producing chevina derivatives of the general formula I 2 in, is n-bn where R.I is alkyl, hydrogen; methyl, methoxyl, - / / or R / and I | h together form the group A where Cd is a carbalkoxy amino group or RH and Rfl together form a group where the thiazole ring may be replaced by a halogen atom; Rj is alkyl C / i-C., Cyclohexyl, phenyl, which may be substituted by one or two halogen atoms, characterized in that, in order to simplify the process, the amine of general formula II NH is R. where R and R. (2 have the indicated meanings, and the amine of the general formula III, R 3 is NHr where R has the indicated meanings, is reacted with phosgene at 20-1 ° C in the medium of halogenated hydrocarbons in the presence of acid-binding agents.
    [2]
    2. A method according to claim 1, characterized in that an alkali metal carbonate is used as an acid binder. Sources of information taken into account during the examination 1. Published for the FRGM 1956157 class. 12 p 9, 1970 (prototype).
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    同族专利:
    公开号 | 公开日
    FR2310344A1|1976-12-03|
    GB1544678A|1979-04-25|
    ES447910A1|1977-10-16|
    BE841538A|1976-09-01|
    HU172341B|1978-08-28|
    CA1068717A|1979-12-25|
    FR2310344B1|1980-06-06|
    DE2618853A1|1976-11-18|
    US4086246A|1978-04-25|
    JPS51133201A|1976-11-18|
    NL7604780A|1976-11-09|
    DE2618853C2|1986-05-22|
    引用文献:
    公开号 | 申请日 | 公开日 | 申请人 | 专利标题
    DE1070617B|
    US1307570A|1919-06-24|Herbert winkel |
    US2936322A|1933-01-18|1960-05-10|Pfanstiel Robert|Process for the preparation of bis urea|
    US2047664A|1935-05-10|1936-07-14|Du Pont|Naphthenyl esters of polycarboxylic acids and their production|
    US2806062A|1937-06-19|1957-09-10|Gehauf Bernard|Process for the manufacture of diphenylurea|
    US2189205A|1938-05-31|1940-02-06|Dow Chemical Co|Carbonates of hydroxybenzoic acid esters|
    US2380130A|1943-01-29|1945-07-10|Us Rubber Co|Antioxidants|
    US2758975A|1952-07-02|1956-08-14|Exxon Research Engineering Co|Synthetic lubricants|
    US2745874A|1953-06-18|1956-05-15|Geigy Ag J R|Insecticidal derivatives of diphenyl urea|
    US3214468A|1959-08-14|1965-10-26|Geigy Ag J R|Bis--carbanilides|
    DE1795682C3|1966-05-06|1975-04-24|Du Pont|
    FR1523597A|1966-05-06|1968-05-03|Du Pont|Substituted 2-aminobenzimidazoles|
    US3773781A|1966-07-18|1973-11-20|Merck & Co Inc|1-substituted-5-nitroimidazol-2-ylalkyl--carbamates|
    IL33182A|1968-11-08|1972-05-30|Du Pont|Solvent process for the preparation of 1-carbamoyl-substituted-2-benzimidazole-carbamates|
    DE1812005A1|1968-11-30|1970-06-18|Bayer Ag|omega-cyanoalkylcarbamyl-benzimidazoles|
    DE2100684A1|1971-01-08|1972-07-20|Badische Anilin- & Soda-Fabrik Ag, 6700 Ludwigshafen|Substituted carbamic acid esters|
    US3920829A|1972-08-30|1975-11-18|Basf Ag|Inflammation inhibiting bis-carbamate composition|US4315861A|1979-11-08|1982-02-16|Chinoin Gyogyszer RT|Process for O-acylating phenol derivatives and acylating compositions for this purpose|
    US4272441A|1980-03-13|1981-06-09|Fmc Corporation|Preparation of carbamates|
    US4323469A|1980-10-28|1982-04-06|Chinoin Gyogyszer Es Vegyeszeti Termekek Gyara R.T.|Process for O-acylating phenol derivatives and acylating compositions for this purpose|
    US4608385A|1981-10-29|1986-08-26|Sumitomo Chemical Company, Limited|Fungicidal N-phenylcarbamates|
    BR8600623A|1985-02-14|1986-10-29|Du Pont|PROCESS FOR THE PREPARATION OF N-METHYL CARBAMATES|
    EP0446514B1|1990-03-16|1993-03-10|Council of Scientific and Industrial Research|Process for the preparation of aryl esters of n-alkyl carbamic acids|
    US5284962A|1992-10-09|1994-02-08|E. I. Du Pont De Nemours And Company|Multistage process for making methyl carbamates|
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    法律状态:
    优先权:
    申请号 | 申请日 | 专利标题
    HU75CI00001572A|HU172341B|1975-05-06|1975-05-06|Process for producing urea derivatives|
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