• 专利附录
  • 专利说明
  • 权利要求
  • 类似技术
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  • 引用文献
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  • 优先权
    • 专利摘要:
    The invention relates to the production of-. benzoic acids, in particular substituted benzoic acids and their. complex esters of the general formula I / HO-A-X COOR, where A is a straight or branched alkyl chain containing 5 carbon atoms; X is an oxygen atom or a direct bond; R-H or lower alkyl, which as having a bactericidal effect. Can be used in medicine. To reveal the pharmacological activity of the compounds of the indicated class, new (I) were obtained. The process is carried out by hydrogenation of a compound of the general formula 02N-CH CH-CH CH CH-CH-X-A-OH where A and X are indicated above coal followed by treatment of the resulting aniline derivative with sodium nitrite in an acidic medium at 0-5 ° C, after which the diazonium compound formed is transferred using copper cyanide to the corresponding benzonitrile, which is subjected to alkaline hydrolysis, and, if necessary,the resulting acid ester. The minimum bactericidal concentration (I) is 250-1000 µg / ml against 10,000-20,000 µg / ml of the known phenylstil alcohol, LDjo 3000. Table 3. O) GS S o: o o ate see
    公开号:SU1296005A3
    申请号:SU843784979
    申请日:1984-08-17
    公开日:1987-03-07
    发明作者:Демарн Анри；Филол Робер；Мосс Мадлен
    申请人:Санофи (Фирма)；
    IPC主号:
    专利说明:

    This invention relates to the field of organic chemistry, specifically to a method for producing benzoic acid derivatives of the general formula
    ABOUT
    11.-l GVA- (O) (I)
    where A is a straight or branched alkyl chain with 5-10 carbon atoms; X is an oxygen or direct atom
    communication; R is hydrogen or an alkyl group
    or lower al kil,
    which can be used as antiseptic drugs or preservatives.
    The purpose of the invention is to obtain new compounds - derivatives of benzoic
    1slots exhibiting increased bactericidal activity with low toxicity.
    Example 1, 4- (3-hydroxypropyl) benzoic acid,
    a) 3- (4-Nitrophenyl) propan-1-ol; To 171.5 g of 3-phenylpropan-1-ol, 95 ml of acetyl chloride are added with stirring over 1 hour. The reflux is heated for 2 hours, the evolved hydrogen chloride and the excess acetic acid are removed. After the temperature of the reaction mixture reaches ambient temperature, it is added dropwise with stirring to 800 ml of fuming nitric acid (, 49), cooled to -25 ° C, the addition is continued for 1 h, at which time the temperature is maintained in the range from -15 to -20 ° C. Then the reaction mixture is poured into 1.5 l of water mixed with crushed ice, and extracted - once with ether, washed three times with water, three times with 10% solution ohm sodium carbonate, then three times with water and the ether phases were dried over magnesium sulphate, then evaporated to dryness under reduced pressure. The residue is dissolved in 800 ml of methanol, then gaseous hydrogen chloride is passed through the solution for 1 hour at 0 ° C and then heated with reflux for 14 hours. After evaporation of the solvent, the residue is dissolved in water-ether, the aqueous phase is decanted, washed twice with water, three times with a saturated solution of sodium bicarbonate and three times with water, then ether

    the dried phase is dried over magnesium sulphate and evaporated to dryness under reduced pressure,
    Obtain 259 g of orange oil, which is purified by chromatography on 3 kg of silica gel in chloroform - get 218 g of orange oil. Yield 95%
    b) 4- (3-0xypropyl) aniline. Dissolve 218 g 3 (4-1 tin)
    propan-1-ol in 500 ml of methanol, 10 g of 10% palladium on carbon, previously moistened with 10 ml of water, are added. The hydrogenation is carried out at a pressure of 40 bar and stirring, it lasts 1.5 hours. It is then filtered through a zeolite, washed with methanol, evaporated to dryness under reduced pressure, and 168 g of chestnut oil are obtained. It is purified by three consecutive chromatographs per 6 kg (total amount) of alumina using dichloromethane as eluent. Obtain 49.2 g powder-light palette color, T, pl, 43-45 ° С “Yield 27% ..
    c) 4- (3-hydroxypropyl) benzonitrile, Pour 49.07 g of the product obtained earlier into 87 ml of concentrated hydrochloric acid, to which 400 g of crushed ice are added, maintaining the temperature in the range
    About - 5 ° C, a solution of 23.15 g of sodium nitrite in 80 ml of water is added dropwise, then, after stirring for 10 minutes, neutralized with 300 ml of 10% sodium carbonate solution.
    0
    five
    0
    five
    At the same time, a solution of copper (I) cyanide is prepared: 40.35 g of copper (I) hydrochloride are suspended in 150 ml of water, a solution of 54 g of sodium cyanide in 80 ml of water is added. Heat is released, - copper (I) chloride dissolves, vegetable -. the thief is discolored. To this cooled to solution, to which 200 ml of benzene is added, is added dropwise over 40 minutes with vigorous stirring to a cooled diazonium solution. After additional stirring for 40 minutes, the mixture is allowed to warm to ambient temperature with stirring, then heated to non-stirring and allowed to cool to ambient temperature.
    It is extracted three times with ether, diluted with water, then with a saturated solution of sodium chloride. The ether phases are dried over magnesium sulfate and evaporated to dryness under reduced pressure. 51 g of oil is obtained
     15.43 g of substance corresponding to the expected product, which is characterized by the following NMR spectrum: ZN 1.3 ppm (T, Hz,
    of red color. Yield 79%.
    NMR product spectrum: 2H between 1.7 and 2.2 ppm (M, -CH.-CH2-CH, j-OH); IE 2.4 ppm (S, .- OH); 2H 2.8 m, d (T, Hz, CN-C H -CH-CH -); 2H 3.6 ppm (T, Hz, -OH); 2H 7.3 ppm (D, Hz, H ortho SI,); 2H 7.6 ppm (D, Hz, H orto CN).
    d) SR 41323.
    dark chestnut color. It is purified 5 -CO, -CH, -CH); ZN between 1.5 and 2.2 ppm chromatography on 1500 g of sily- (bulk, OH — CH — CH — CH — CH,); 2H Kagel, koloha and in toluene and in ka-2.7 ppm (T, Hz, OH — CH — CH, a mixture of tolu- is used as the eluent); 2H, 3.6 ppm, (Hz, ol-ether (9-1 by volume). PoluchayutoN-CH-CH, s; -CH,); 2H 4.3 ppm
    41.6 g of pure product in the form of an oil; o (O, Hz, -CO-CH. -CH); 2H 7.2 ppm
     (D, Hz, H ortho CHj); 2H7.9 ppm
    (D, Hz, H ortho C02).
    Example 3. 4- (2-Oxybutyl) benzoic acid. 5a) 1-Fe1Shlbutan-2-ol.
    To 2.92 g of magnesium chips is added dropwise under a nitrogen atmosphere at a rate sufficient to maintain a weak restocking solution, 7.5 ml. Dissolve 41 g of (20) ethyl acetate in 50 nl of anhydrous ester product in 150 ml. Alcohol is mixed. Still, 15 g of sodium hydroxide is added to the atmosphere, followed by nitrogen, for 2 hours at the same time it is heated with reflux during the course of the environment, then at 17 hours with stirring. After cooling dropwise, 9.4 ml of phenylacetylation is evaporated to dryness with poi-25 aldehyde and left under mixed pressure, the residue is dissolved in water and acidified with concentrated hydrochloric acid to approximately. It is extracted twice with ether, washed twice with water, then with a saturated solution of sodium chloride. After that, the ether phases are dried over magnesium sulphate and evaporated to dryness under reduced pressure. Yellow crystals are obtained, which are percrystal1: lysing from ether-hexane.
    2 hours at ambient temperature.
    Then it is decomposed with the action of 200 ml of 20% ammonium chloride, cooled down, and extracted three times with ether. After washing three times with water, the ethereal phases are dried over magnesium sulfate and evaporated to dryness under reduced pressure to give 12.2 g of a pale yellow oil.
    33.7 g of a cream-colored powder are obtained. T. pl, 138-14 ° C.
    Example 2. Ethyl 4- (3-hydroxypropyl) benzoate,.
    13.5 g of the product obtained earlier (SR 41945) is dissolved in 200 ml of absolute ethanol and 6 ml of thionyl is added dropwise with stirring. Example 4. Ethyl 4 (2-hydroxybutyl) benzoate.
    chloride. When the temperature of the reaction is 5 This product is obtained from the acid, the mixture reaches the temperature surrounding the example 3, and the characterizing medium is heated with reflux by the following NMR spectrum: 3H
    , 0.9 ppm (T, Hz, -CH (OH) -); 6P between 1.1 and 1.7 ppm
    with stirring for 6 hours, then left overnight at ambient temperature. Dissolve that 50 (massive, ,, - CH (OH) -CO-CH-CTC); 2H between 2.6 and 2.9 ppm, (M, CH (OH)); W between 3.5 and
    evaporated under reduced pressure, then extracted three times with ether, washed twice with a saturated solution of sodium bicarbonate, twice with water, then with a saturated solution of sodium chloride. Then the ether phases were dried over magnesium sulfate and evaporated to dryness under reduced pressure.
    3.9 ppm (M, (OH) -CH,); 2H 4.3 ppm (O, Hz, —CO —CHj — CH h); 55 2H 7.3 ppm (D, Hz, H ortho CH,); 2H 8 n.d. (D, Hz orto CO).
    Example 5. 4- (4-0-hydroxybutyl-oxy) benzoic acid.
    a) 1- (4-Nitrophenoxy) -4-bromobutane.
    г- 12960054
     15.43 g of substance corresponding to the expected product, which is characterized by the following NMR spectrum: ZN 1.3 ppm (T, Hz,
    t 5 -CO, -CH, -CH); ZN between 1.5 and 2.2 ppm and- (massive, OH — CH — CH — CH — CH,); 2H 2.7 ppm (T, Hz, OH — CH 25 aldehyde and left under stirring
    2 hours at ambient temperature.
    Then it is decomposed with the action of 200 ml of 20% ammonium chloride, cooled down, and extracted three times with ether. After washing three times with water, the ethereal phases are dried over magnesium sulfate and evaporated to dryness under reduced pressure to give 12.2 g of a pale yellow oil.
    b) 4- (2-hydroxybutyl) benzoic acid,
    Then, according to the methods described in. Example 1, an acid is obtained, which is recrystallized from a mixture of ether-hexane, T. IUI, 103-106 0.
    Example 4. Ethyl-4 (2-hydroxy-butyl) benzoate.
    This product was obtained from the acid obtained in Example 3 and is characterized by the following NMR spectrum:
    -STC); 2H between 2.6 and 2.9 ppm, (M, CH (OH)); W between 3.5 and
    3.9 ppm (M, (OH) -CH,); 2H 4.3 ppm (O, Hz, —CO —CHj — CH h); 55 2H 7.3 ppm (D, Hz, H ortho CH,); 2H 8 n.d. (D, Hz orto CO).
    Example 5. 4- (4-0-hydroxybutyl-oxy) benzoic acid.
    a) 1- (4-Nitrophenoxy) -4-bromobutane.
    83 ml of 1,4-dibromobutane is added to a solution of 4-nitrophenrel in 275 ml of water, then 49.5 mp 10 n of sodium hydroxide solution are added dropwise with stirring. Heat with refpux under stirring for 24 hours.
    After cooling, the mixture is extracted three times with ether, washed six times with 1N sodium hydroxide solution and three times with water. The ether phases are dried over sodium sulfate and evaporated, the insoluble residue is filtered off. The filtrate is evaporated to dryness, and the residue is distilled off in vacuum (0.05 mmHg), after trituration in hexane, crystals are obtained, which are filtered, washed in hexane, and dried in a vacuum desiccator. 75 g of a creamy colored paste are obtained. Yield 55%
    b) - (4 Nitrophenoxy) -4-adatilok-CH6yTaii,
    I
    Dissolve 75 g obtained in (a)
    of the product in 80 MP glacial acetic acid, 45 g of anhydrous sodium acetate is added, then it is heated with refpux for 15 hours with stirring. The reaction mixture was drunk in 1 liter of ice water, to which 500 ml of ether was added, and neutralized to 5 with solid sodium carbonate. After extracting three times with ether and washing three times with water, the ether phases are dried over magnesium sulphate and evaporated to dryness, the residue is distilled off in vacuo.
    (CH J, OH
    ((HE N
    O (CH ,,) 50Н (CH,) 50Н
    (CH SNSSYU-pSzN, (CH) 50H
    Obtain 70 g of orange oil, Yield 100%.
    c) 1- (4-Nitrophenoxy) butan-4-ol.
    Dissolve 70 g of the product obtained in (b) in 300 ml of methanol, add 30 ml of 10N sodium hydroxide solution, then heat with refpux with stirring for 4 hours. After distilling off the methanol, the residue is dissolved in a water-ether mixture extracted three times with ether, washed three times with a saturated solution of sodium chloride. The ether phases are then dried over magnesium sulphate and evaporated to dryness. The crystals formed are triturated in hexane, phylated, washed with hexane and dried in a vacuum desiccator.
    48.8 g of pale yellow crystals are obtained, mp, 53-55 ° C, d) 4- (4-Oxybutyloxy) benzoyl
    acid.
    According to the procedure described in Example 1, the following compounds are then prepared:
    4- (4-hydroxybutloxy) aniline, T, pl. 56-58 С,
    4- (4-hydroxybutyloxy) benzonitrile. T. pl. 54-58 ° C.
    4- (4-hydroxybutyloxy) benzoic acid. T. pl. 143-145 C after recrystallization from ether ..
    In a similar way, compounds according to the proposed method are obtained, given in Table. 1. They are characterized by an NMR spectrum or m, mp, measured, after recrystallization from ethanol-hexane,
    Table 1
    one
    3 5 2 4 5
    104-106 ° С 105-1
    NMR NMR NMR
    The method of obtaining and characteristics of the products table. 1 the following.
    Compound I is prepared according to Example 1, Step a-nitration of 5-phenyl-1-pentanol. Step 5: Reconstitution of a nitro derivative. General output in these two phases. 38%. Stage 6- production of cyano derivative, yield 68%. Stage g hydrolysis of nitrile, yield 82%.
    Calculated,%: C 69.23; H 7.69.
    Found,%: C 69.28; H 7.87.
    TLC: Rf 0.37 (methylene ethyl acetate-acetic acid 48:48:: 4.0 v / v).
    Compound II is prepared according to Example 3. Stage a-action of methyl bromide on phenylacetate dehydration. From 28.8 g of phenyl acetaldehyde, 37.35 g of 1-phenyl-2-pentanol yield 93% .- Step 8- nitration. From 39.65 g of 1-phenyl-2-pentanol, 31.9 g of the nitro derivative are obtained, i.e. yield 64%. Stage 6 - catalytic reduction of 31.8 g of the nitro derivative gives 15.15 g of the amine derivative 56% yield. Stage g - preparation of cyano derivative, yield 66%. Of 1 1.57 amino derivatives, 8.02 g of cyano derivative are obtained, yield 66%. Step d - hydrolysis of the nitrile, yield 83%. From 8 g of the nitrile, 7.28 g of acid is obtained.
    Calculated,%: C 69.23; H 7.69.
    Found,%: C 69.18; H 7.90.
    TLC: RJ 0.45 (chloroformmethanol 85: 15 sgl./about.).
    Compound III is prepared according to Example 5. Step a. obtaining 1- (4- -nitrophenoxy) -5-bromopentane. From 69.5 g of 4-nitrophenol, 130 g of the expected product is obtained, yield 90%. Step S- Preparation of 1- (4-nitrophenoxy) -5-acetoxypentane. 130 g of the indicated brominated derivative gives 88.5 g of the acetoxy derivative, yield 74%. Step 6- 5- (4-nitrophenoxy) - -pentanol. 88.5 g of the previous derivative gives 64.5 g of alcohol (yield 87%). Stage d - reduction of the nitro-compound of 64.5 g of the nitro-derivative gives 43.3 g of the amino derivative, yield 77%. Step d- getting nitrile. From 37.05 g of this derivative, 20.4 g of nitrile are obtained, yield 52%, Step, e-hydrolysis of nitrile. From 13 g of nitrile, 9.35 g of acid is obtained, yield 66%,.
    five
    ABOUT
    five

    five

    Calculated,%: C 64.29; H 7.04.
    Found,%: C 64.49; H 7.14.
    TLC: R 0.30 (chloroform: methanol 95: 5 v / v,).
    Compound IV is obtained according to Example 2, 5.17 g of ethyl ester is obtained from 5.2 g of acid (Compound I), yield 87%.
    NMR spectrum: 9H between 1, 1 and 1.9 ppm (massive, OH-CH - (CH,) s-CH2 and.); 2H 2,6 ppm (T, Hz,); 2 and 3.6 ppm, (T, J 6 Hz, OH — CHj — CH, -); 2H 4.3 m, d (O, 3-7 Hz, -CO,); 2H 7.2 m. (D, Hz, H ortho CHj); 2H 8 ppm (D, Hz, H ortho COg),
    Compound V was prepared according to Example 4. 4.29 g of ethyl ester was obtained from 4.8 g of acid (Example 2), yield 79%.
    NMR spectrum: PI mulsda O, 7 and 1.7 ppm, (massive, CH j — CH —CH — CH (OH) —CO,. —H — CH, —CH 3); 2H between 2.6 and 2.9 ppm (M, -CH (OH) -CH,., - CgH,); W between 3.6 and 4 ppm, (M, -SP2-СЫ (ОН) -СН); 2H 4.3 ppm (O, Hz, 2H, 7.3 ppm CD, Hz, ortho CH,); 2H 8 ppm (D, Hz, H ortho CO).
    Compound VI was prepared according to Example 5, 3.2 g of ester was obtained from 5.25 g of acid, yield 54%.
    I D -spektp: WN 1.3 ppm, (T, J = 7 Hz,, -CH.); 6H between 1.4 and 1.9 ppm, (massive, OH-CH. -CH5, -CH,); 2H 3.6 m.d, (T, Hz, -CH.-CH-0-CgHJ; 2H 4 m, d, (T, Hz, OH-CH-CH -); 2H4, Sm.d. (O , Hz,); 2H 6.9 ppm (D, Hz, N metha CO); 2H 8 ppm (D, Hz, H ortho CO.a),
    The bactericidal activity of the products according to the invention was investigated on various strains by the following method.
    The bacterial inoculum is brought into contact with the test product at various dilutions for a certain period of time. At the end of the contact, an aliquot portion of the bacterial suspension-product mixture is placed on the surface of the agar culture medium containing a substance that neutralizes the bactericidal activity of the product.
    The remaining bactericidal concentration is the minimum product concentration at which
    9 1
    no more bacterial growth is observed. This concentration is expressed in mg / ml.
    The following bacterial strains were selected for the studies: 1 - Escherich coli CNCM 54125, 2 - Klebsiella pneumonic capsule R030, 3 - Pseudo-monas aeruginosa CNCM A22, 4 - Streptococcus faccalis CNCM 5855, 5 - Staphylococcus aurexis CNCM 53154,
    The second strain is cultivated on Eré de Worgel Ferguson, the rest on Tryptic Soy Agar-Difco (ISA) medium,
    After cultivation for 24 hours at 37 ° C, the grown bacteria are collected using glass beads and 10 ml of a diluent containing 1 g of tryptone and 8.5 g of sodium chloride in 1000 ml of distilled water. The resulting suspension is stirred and the light transmittance is measured with a spectrophotometer at 620 nm: strain 1 - 70%, strain 2 - 80%, strain 3 - 70%, strain 4 - 60%, strain 5 - 60%,
    Bacterial knokut corresponds to 1/20 suspension of this bacterial suspension.
    Plates with caps are placed on the product to be examined with varying degrees of dilution. These portions of the diluted product are brought into contact with various bacterial suspensions using a multi-point inoculum of the Steers type. After contact for 20 min, aliquots are transferred using this inoculum to the surface of the TSA agro medium placed in a Petri dish containing neutralizer activity, namely, 20 g of lubrol W, 2.5 g of Theen-80 and 2.5 g of sodium thiosulfate in 1000 ml of TSA (Difco), a control experiment to determine the effectiveness of the neutralizer is carried out for each product by placing it on the surface of the cultures. aliquot portion of the diluted portion of the test product. After drying, the appropriate inoculum is placed in the same place. A control op inoculum was performed on an agar
    environment with neutralizer and without neutralizer. The counting is performed after the 48-hour incubation period at 3-7 ° C.
    The minimum bactericidal concentration (MBC), µg / ml, is presented in Table. 2,






    ten
    I 500 750 250 500 500 III 600 200 400 800 600

    500 800 1000 1000 1000 250 100 600 400 100
    1500 10000 100002000015000
    The results show that the products according to the proposed method have a wide spectrum of activity in relation to the tested bacterial strains. The fungicidal activity of these products is also determined by the method of sequential dilutions on an agar medium.
    Prepared stock solutions of various products using 20% tetraglycol, starting from these master solutions: whole solutions were obtained, a gamma of diluted samples exponentially in a 1/2 ratio, 2 ml of each of these x diluted pro were distributed in Petri dishes and added 1.8 ml agar medium Sabouraud Dektrose Agar (Difco).
    The inoculum was prepared for yeast by diluting 1/20 of the culture aged for 48 hours with Sabouraud liquid medium. For dermatophytes and infecting fungi, the inoculum was prepared by collecting, with POMOTSI, 5 ml of Sabouraud liquid medium, cultures on Sabouraud agar medium.
    The inoculum is placed on the surface of the petri dishes with the help of a multipoint inoculum. The counting was carried out after a 48 hour incubation period at 27 ° C for yeast, after 7 days, incubation at 27 ° C for dermatophytes and after 4 days. incubation at 27 ° C for infectious fungi. The minimum inhibitory concentration (MIC), expressed in µg / 1 L, is the lowest concentration at which no growth is observed,
    In tab. 3 shows the results of fungicidal activity obtained for various products according to the invention.
    The experiments were performed with 22 yeast strains, 18 strains of dermatophytes and 8 strains of infective fungi. The results show the extremes obtained for each category.
    Table 3
    These results show that the products according to the invention have a good activity against the fungi tested.
    The tolerance of the products according to the invention was tested on guinea pigs. The animals were shaved on both sides of the midline of the back, shaving repeated every two days. Groups of 6 animals receive in the shaved section O, 2 ml of an aqueous or alcoholic solution of the product according to the invention. If the product is used as an alcohol solution, alcohol is applied to one control group of animals.
    To study the pre-treatment, the treatment was performed once a day, six days a week for three weeks. Skin Q is observed with respect to various
    the appearance of erythema, skin rash or hyperkeratosis, the intensity of which is estimated on a specific scale.
    Sensitivity test
    species of tested bacteria. In addition, they have low toxicity, good tolerance, and sensitizing effects,
    carried out on the same animals after a phototoxic or photo exposure of a two-week break; Treatment-allergic action lasts one week; therefore, products according to
    identical to that considered. The evaluation of the invention can be varied according to the same criteria and used as an antiseptic scale as the assessment of local tolerance.
    It has also been investigated whether the products according to the invention have a photo-toxic or photo-allergic effect on guinea pigs.
    None of the studied products showed poor tolerance, sensitizing effects, or photo-Otoxic or photoallergic effects on guinea pigs.
    Oral administration of acute toxicity was performed in mice. This study was carried out on 5 mice of the genus C1 1 obtained from Charles River. Each group consists of five animals weighing 24-30 g, containing xc in one cage.
    Animals were not given food for 0 to 6 hours before treatment. For each study, the product suspended in a 10% w / w solution of gum arabic was forcibly injected using an esophagus probe,
    5 4 hours after the forced introduction of the product, the animals received food and they were monitored for 14 days, on the day of the introduction of the product,
    0 During this period, mortality is noted in each group of experimental animals, and where possible, a lethal dose of jo is determined (according to the method of Litchfield and Wilcoxon,
    The following results were obtained, expressed in mg of the test substance per kg of animal weight,
    IIIDL O 3 000
    IVDL O 3 000 VI DL O 3 000 Compounds according to the invention
    exhibit a level of activity that is of great interest to us 1y, and 5 they gain when compared with the assets of the most important antiseptics used in practice.
    In addition, the products according to the invention have a homogeneous AK5
    0
    species of tested bacteria. In addition, they have low toxicity, good tolerance and lack sensitizing effects.
    13
    1296005
    , preserving or disinfecting agents,
    In particular, they can be used as antiseptics or for the preparation of drugs, for example, for treating impetigo, acne, infectious dermatoses, open infectious ulcers, closed infections, such as boils, felons, impetiginized nets, etc. They will also be able to use dp for preventive purposes, such as preparing the operating floor, treating the hands of the surgeon or treatment
    In the field of veterinary medicine, the products according to the invention can be used either as antiseptics (for example, dp prevention of mastitis), or as disinfectants (disinfecting sheds, tools, ...), as well as in the field of agricultural food production.
    Finally, good tolerance and weak toxicity make it possible to apply them as preservatives not only in the field of pharmaceuticals and cosmetology, but also in the field of agricultural production of food products.
    The various galley compositions of the products according to the invention can be obtained depending on the chosen application.
    Example 6,
    Antiseptic alcohol solution I
    Alkyldimethylcarboxymethylamine (30%
    solution) 0.5 g
    Ethylene oxide condensate and propylene glycol L621 g
    Lactic acid or
    sodium hydroxide to pH 6,
    Ethyl alcohol 100 g
    Example 7, The product according to the invention can be used as a preservative in the manufacture of shampoos of the following composition, g:
    Potassium palmitate and
    amino acids 20
    Sodium alkyl sulfates 2
    Diethanolamide copra5
    0,200
    0.5 g
    L anoles l ad he t at
    II
    Sodium hydroxide
    Purified water
    0.150 To pH 7 To 100
    J4
    r
    5 d
    Q


    e
    five
    Example 8. The product according to the invention can be applied as a preservative in the production of a cream-emulsion of the following composition, g:
    Thick Vaseline Oil6
    A mixture of cetostearic alcohol and oxymethylated cetostearic alcohol9
    Anhydrous monosodium phosphate0,300
    Disodium tetracemat0,010
    Vaseline 15
    II0,100.
    Phosphorus gag1slota Do pH 4.5
    Purified water up to 100
    Example 9, the product according to the invention can be used as a preservative in the manufacture of cosmetic cream of the following composition, g:
    Collagen, 500
    Carboxypolymethylene 9340,400
    Hydrogenated lanolin 4 Perhydroscalene20
    Monopalmitate polyoxymethlylated sorbitol2
    IV0,150
    Lactic acid or sodium hydroxide Up to 6.5
    Purified water up to 100
    Example 10. Antiseptic liquid foam detergent composition, g:
    VI0,3
    Alkyldimethylcarboxymethylamine (30% solution) 15
    Disodium tetracemat 0,1
    Propylene glycol 20
    Sodium Hydroxide Do, 8
    Purified water up to 100
    PRI me R 11. Antiseptic liquid foam detergent composition, g:
    I0,2
    Paraffinsulfonate
    rub 15
    Sodium hydroxide or
    lactic acid up to pH 5.2
    Purified water up to 100
    Example 12. Disinfectant for inert surfaces of the composition, g:
    IV0.5
    Dodecyl dimethylcarboxydimethylamine 20 Disodium tetracell .2
    Lactic acid up to pH 3.5
    Purified water up to 100
    权利要求:
    Claims (1)
    [1]
    Invention Formula
    The method of obtaining benzoic acid derivatives of the general formula
    ABOUT
    where A is a straight or branched 20 alkyl chain containing 5 carbon atoms; ,
    X is an oxygen or direct atom
    communication;
    R is H or lower alkyl, characterized in that the compound of the general formula.
     OVX-A-OH
    where X and A are as indicated,
    subjected to catalytic hydrogenation in methanol in the presence of a palladium-carbon catalyst, followed by treating the resulting aniline derivative with sodium nitrite in an acidic medium at 0-5 C, after which the diazonium compound formed is converted with copper cyanide to the corresponding benzonitrile, which is subjected to alkaline hydrolysis, and then, if necessary, converting the resulting acid to ether.
    Editor B, Danko
    Compiled E, Utkina
    Tehred L.Oleynik Proofreader N. King
    Order 630/63 Circulation 372 Subscription VNIIPI USSR State Committee
    for inventions and discoveries 113035, Moscow, Zh-35, Raushsk nab, 4/5
    Production and printing company, Uzhgorod, st. Project, 4
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    EP0125827A1|1984-11-21|Polyether bisbiguanides
    RU2030394C1|1995-03-10|N-allyl-n- | -anthranilic acid 4-bromoanilide showing antiinflammatory and analgetic activity
    RU2084441C1|1997-07-20|Method of synthesis of difficultly soluble carboxylic acid, amine and amino acid acid-additive salts
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    SU1719398A1|1992-03-15|N-oxide of 4-amino-3,5,6-trichloropyridin-2-carbonic acid as a herbicide
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    Srinivasan0|Available online through
    NAIK et al.0|Synthesis and In Vitro Antioxidant Evaluation of Some Indole-2-carboxylic Acid-Aryl Amine Conjugates
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    同族专利:
    公开号 | 公开日
    EP0135433A1|1985-03-27|
    AU562423B2|1987-06-11|
    EP0135433B1|1989-01-18|
    PT79105A|1984-09-01|
    PT79105B|1986-07-17|
    JPS60120801A|1985-06-28|
    DK390384A|1985-02-19|
    FI843264A0|1984-08-17|
    DK387884D0|1984-08-10|
    NO843296L|1985-02-19|
    DD222005A5|1985-05-08|
    NO158622C|1988-10-12|
    EP0135432B1|1988-06-01|
    IL72669D0|1984-11-30|
    FI843264A|1985-02-19|
    NZ209264A|1987-02-20|
    IL72668D0|1984-11-30|
    NO158622B|1988-07-04|
    US4691043A|1987-09-01|
    US4946868A|1990-08-07|
    JPS60166645A|1985-08-29|
    KR850001722A|1985-04-01|
    DE3471587D1|1988-07-07|
    CA1254226A|1989-05-16|
    EP0135432A1|1985-03-27|
    YU143184A|1986-10-31|
    IL72668A|1988-03-31|
    CA1271416A|1990-07-10|
    ES535694A0|1985-05-16|
    FI82237C|1991-02-11|
    FR2550785B1|1985-12-06|
    IL72669A|1988-12-30|
    MA20205A1|1985-04-01|
    HU191944B|1987-04-28|
    AU3194784A|1985-02-21|
    AT34662T|1988-06-15|
    FI82237B|1990-10-31|
    GR80119B|1984-12-14|
    KR910007365B1|1991-09-25|
    HUT34947A|1985-05-28|
    DK390384D0|1984-08-14|
    ZA846424B|1985-03-27|
    DE3476160D1|1989-02-23|
    ES8505332A1|1985-05-16|
    FR2550785A1|1985-02-22|
    AU3194884A|1985-02-21|
    AU565899B2|1987-10-01|
    ZA846425B|1985-03-27|
    DK387884A|1985-02-19|
    CS244825B2|1986-08-14|
    NZ209265A|1986-12-05|
    引用文献:
    公开号 | 申请日 | 公开日 | 申请人 | 专利标题
    GB1050136A|
    IL45396D0|1973-08-23|1974-11-29|Beecham Group Ltd|Pharmaceutical compositions containing aryl aralkyl ether and thioether derivatives,certain such novel compounds and their preparation|
    CA1045635A|1973-11-27|1979-01-02|Kyowa Hakko Kogyo Co.|.beta.-PHENOXY OR SUBSTITUTED PHENOXY ETHANOL COMPOUNDS|
    GB1511645A|1974-05-31|1978-05-24|Univ Ife|Sickle cell anaemia treatment|
    US4433161A|1982-03-08|1984-02-21|Ethicon, Inc.|Methyl p- benzoate and method of preparation|DE3500972A1|1985-01-14|1986-07-17|Henkel Kgaa|SEBOSUPPRESSIVE COSMETIC AGENTS, CONTAINING ALKOXY OR ALKYLBENZYLOXY BENZOESAEUREN OR THEIR SALTS|
    WO1993012782A1|1991-10-31|1993-07-08|Elford Howard L|Method of treating viral diseases|
    DE4225794C2|1992-07-31|1994-12-08|Schuelke & Mayr Gmbh|Tb-active carboxylic acids|
    DE4301295C2|1993-01-15|1999-04-08|Schuelke & Mayr Gmbh|Aqueous disinfectant concentrate and disinfectant based on aldehyde and alcohol and their use|
    DE4447361A1|1994-12-21|1996-06-27|Schuelke & Mayr Gmbh|Biocidal alcohols, their production and their use|
    AU2003262769A1|2002-08-20|2004-03-11|Pinnell, Doren M|Methods for treating fungal infections|
    WO2015120216A1|2014-02-07|2015-08-13|Gojo Industries, Inc.|Compositions and methods with efficacy against spores and other organisms|
    US9578879B1|2014-02-07|2017-02-28|Gojo Industries, Inc.|Compositions and methods having improved efficacy against spores and other organisms|
    WO2018143911A1|2017-01-31|2018-08-09|Kimberly-Clark Worldwide, Inc.|Antibacterial composition including benzoic acid ester and methods of inhibiting bacterial growth utilizing the same|
    法律状态:
    优先权:
    申请号 | 申请日 | 专利标题
    FR8313445A|FR2550785B1|1983-08-18|1983-08-18|NOVEL COMPOSITIONS WITH ANTIMICROBIAL ACTIVITY CONTAINING BENZOIC ACID DERIVATIVES, THEIR PREPARATION METHOD, THEIR USE AS DISINFECTANT OR PRESERVATIVE DRUGS|
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