The method of obtaining simple diaminopropionic ether or simple gidroksiaminopirimidinov ether
(57) Abstract:The invention relates to a new method of obtaining simple diaminopropionic ether or simple gidroksiaminopirimidinov ester by the interaction of dipropyleneglycol with ammonia and hydrogen at 150-190oC and at a pressure of 75-250 bar in the presence of Nickel-copper-chromium catalyst containing 35-58 mol.% Nickel, 10 to 30 mol.% copper and 12-55 mol.% chromium. The method allows to obtain products without changing the structure of the parent compounds in the rearrangement. The invention relates to a method for simple diaminopropionic ether or simple gidroksiaminopirimidinov ether by catalytic amination of dipropyleneglycol.From U.S. patent 3654370 know getting polyoxyalkylene of polyoxyalkylene by reacting with ammonia and hydrogen in the presence of Nickel catalyst. However, it will be rearranged polyoxyalkylene skeleton (see Japan patent 49-29313 (1974)).The present invention is to develop a method by which you can obtain a simple diaminodiphenyl ether and simple hydroxyaminobuteroyl ester with high yield without aetsa way to obtain simple diaminopropionic ether or simple gidroksiaminopirimidinov ester by the interaction of dipropyleneglycol with ammonia and hydrogen at elevated temperature and under pressure in the presence of Nickel catalyst, the distinctive feature of which is that the process is carried out at 150-190oC and at a pressure of 75 to 250 bar in the presence of a Nickel catalyst nickelode-chromium catalyst containing 35-58 mol.% Nickel, 10-30 mol. % copper and 12-55 mol.% chrome.According to the invention interact with the corresponding diamines or amine alcohols can be subjected to, for example, commercially available standard dipropyleneglycol (representing a mixture of 1,1'-oxydi-2-propanol, 2-(2'-hydroxypropoxy)-1-propanol and 2,2'-oxide-1-propanol).The interaction can be performed in a flow reactor, provided with a layer of catalyst at 150 - 190oC and at a pressure of 70 to 250 bar.As the catalyst preferably take gidrirovannoe hydrogen mixture of Nickel oxide, copper oxide and chromium oxide containing 35-58 mol.% Nickel, 10 to 30 mol.% copper and 12-55 mol.% chromium. Typically, the catalyst is used as the fixed layer. It exists in the form of particles with a size of about 1 to 10 mm, for example in the form of solid tablets.Such catalysts are known in General (see, for example, React. Kinet. Catal. Lett., volume 44; 1, 215-222 (1991)).As raw materials use of clean or p is a mixture of simple diaminopropionic ether and simple gidroksiaminopirimidinov ether, the molar ratio ranging from 1:1.5 to 1:20. In that case, if using the proposed method want to get clean simple diaminopropionic the ether, or as raw materials can use a mixture of dipropyleneglycol and simple gidroksiaminopirimidinov ether.Obtained according to the invention compounds can be used as intermediates to obtain plastics.Example 1
Using a flow reactor with a fixed catalyst bed. In the reactor serves 100 ml of catalyst containing 55 mol.% Nickel, 18 mol.% copper and 27 mol.% chromium. The catalyst is subjected to reduction with a mixture of nitrogen and hydrogen.Then injected into the reactor per hour 100 l of hydrogen measured under normal conditions), 200 ml of liquid ammonia and 13 ml of liquid dipropyleneglycol. The reaction is carried out at 170oC and at a pressure of 200 bar. Exemptions from ammonia, the reaction product contains of 14.3 wt.% simple diaminopropionic ether, 22,1 weight. % simple gidroksiaminopirimidinov ether, a 27.4 wt.% dimethylmorpholine, to 15.4 wt.% water and 20.7 wt.% dipropyleneglycol. Conversion dipropyleneglycol is 76,9% with relative selectivity for simple diaminopropionic ether, the composition is bringing 32,4 mol.%.In the distillation distillation pure simple diaminodiphenyl ether (boiling point 74-75oWith 13 mbar) and a simple hydroxyaminobuteroyl ester with a purity of above 99 wt.%.Example 2
Danny example by analogico example 1, and using the same catalyst. To the reactor is introduced into h 100 l of hydrogen measured under normal conditions), 200 ml of liquid ammonia and 13 ml of liquid dipropyleneglycol. The reaction is carried out at 150oC and at a pressure of 200 bar. Free from ammonia, the reaction products include a 0.9 wt.% simple diaminopropionic ether, and 19.8 wt.% simple gidroksiaminopirimidinov ether, 3.3 wt.% dimethylmorpholine, 4 weight. % of water and 72 wt.% dipropyleneglycol. Conversion dipropyleneglycol thus is 25.6 wt.% with relative selectivity for simple diaminopropionic ether component of 3.1 mol.%, and relative selectivity for simple gidroksiaminopirimidinov ether, component 80,5 mol.%.Example 3
This example is carried out analogously to example 1. In the reactor serves 200 ml of catalyst containing 38 mol.% Nickel, 11 mol.% copper and 51 mol.% chromium. As described in example 1, the catalyst is subjected to the reduction of the s conditions), 400 ml of liquid ammonia and 26 ml of liquid dipropyleneglycol. The reaction is carried out at 175oC and at a pressure of 200 bar. Free from ammonia, the reaction products consist of 10.7 wt.% simple diaminopropionic ether, 26,7% wt. simple gidroksiaminopirimidinov ether, 26,7% wt. dimethylmorpholine, 14.9 weight. % water and 20.9 weight. % dipropyleneglycol. Conversion dipropyleneglycol is of 76.8 wt.% with relative selectivity for simple diaminopropionic ether component of 15.7 mol.%, and relative selectivity for simple gidroksiaminopirimidinov ether, component 39 mol.%.Example 4
This example is carried out analogously to example 3, and take the same catalyst with the only difference that instead of dipropyleneglycol using a mixture of 53 weight. % dipropyleneglycol and 47 wt.% obtained from the reaction of simple gidroksiaminopirimidinov ether. Free from ammonia, the reaction product contains about 7.6 wt.% simple diaminopropanol ether, 45,9% wt. simple gidroksiaminopirimidinov ether, 10.6 wt.% the research, 5.5 wt.% water and 30.4 wt.% dipropyleneglycol. That is, the conversion dipropyleneglycol is 40,4 weight. % with relative selectivity towards simple diamenter is simple gidroksiaminopirimidinov ester by the interaction of dipropyleneglycol with ammonia and hydrogen at elevated temperature and under pressure in the presence of Nickel catalyst, characterized in that the process is carried out at 150-190oC and at a pressure of 75-250 bar in the presence of a Nickel catalyst, Nickel-copper-chromium catalyst containing 35-58 mol. % Nickel, 10-30 mol. % copper and 12-55 mol. % chromium.
FIELD: organic chemistry, medicine.
SUBSTANCE: invention reports about preparing new substituted derivatives of 2-dialkylaminoalkylbiphenyl of the general formula (I):
wherein n = 1 or 2; R1 means cyano-group (CN), nitro-group (NO2), SO2CH3, SO2CF3, NR6aR7a, acetyl or acetamidyl; R2 means hydrogen atom (H), fluorine atom (F), chlorine atom (Cl), bromine atom (Br), cyano-group (CN), nitro-group (NO2), CHO, SO2CH3, SO2CF3, OR6, NR6R7, (C1-C6)-alkyl, acetyl or acetamidyl being alkyl can comprise one or more similar or different substitutes taken among halogen atom or hydroxy-group; or R1 and R mean in common group -OCH2O, -OCH2CH2O, CH=CHO, CH=C(CH3)O or CH=CHNH; R3 means H, F, Cl, Br, CN, NO2, CHO, SO2CH3, SO2CF3, OR6, NR6R7, (C1-C6)-alkyl, acetyl or acetamidyl being alkyl can comprise one or more similar or different substitutes taken among halogen atom or hydroxy-group; R4 and R5 have similar or different values and mean hydrogen atom (H) or unsubstituted (C1-C6)-alkyl; R6 and R7 have similar or different values and mean hydrogen atom (H) or unsubstituted (C1-C6)-alkyl; R6a means hydrogen atom (H) or unsubstituted (C1-C6)-alkyl; R7a means unsubstituted (C1-C6)-alkyl as their bases and/or salts of physiologically acceptable acids, with exception of compound representing 4-chloro-2'-dimethylaminomethylbiphenyl-2-carbonitrile and to a method for their preparing. Derivatives of 2-dialkylaminoalkylbiphenyl can be used in medicine for treatment or prophylaxis of pains, inflammatory and allergic responses, depressions, narcomania, alcoholism, gastritis, diarrhea, enuresis, cardiovascular diseases, respiratory ways diseases, cough, psychiatry disorders and/or epilepsy.
EFFECT: valuable medicinal properties of compounds.
13 cl, 2 tbl, 43 ex
FIELD: organic chemistry, chemical technology.
SUBSTANCE: invention relates to a method for preparing amido acid ester that is useful as an intermediate substance in synthesis of agrochemical preparation. Invention relates to amido acid ester represented by compound of the general formula (7): wherein A represents substituted or free lower alkylene group, and so on; R1 represents substituted or free lower alkyl group, and so on; R3 represents hydrogen atom or lower alkyl group. Method for preparing amido acid ester involves interaction of amino acid represented by compound of the general formula (1): in presence of water with halogenated carboxylic acid ester represented by compound of the general formula (2): wherein X represents halogen atom with formation of amide represented by compound of the formula (3): Then amide compound interacts with halogenated carboxylic acid ester represented by compound of the general formula (4): wherein R2 represents substituted or free lower alkyl group, and so on; X represents halogen atom with preparing carboxylic acid mixed anhydride represented by compound of the general formula (5): Then carboxylic acid mixed anhydride interacts with amine compound represented by compound of the general formula (6): A, R1 and R3 have the same values as given above; Het represents substituted of free heterocyclic group. Invention provides reducing economic indices of the process.
EFFECT: improved preparing method.
9 cl, 2 ex
FIELD: industrial organic synthesis.
SUBSTANCE: invention provides improved 2,7-bis[2-(diethylamino)ethoxy]fluorenone dihydrochloride production process comprising stages of sulfurization of fluorenone followed by neutralization of obtained reaction mass, isolation of purified fluorenone-2,7-disulfonic acid disodium salt, "alkaline melting" of this salt in presence of sodium nitrate to form 4.4'-dihydroxydiphenyldicarboxylic acid, cyclization to form 2,7-dihydroxyfluorene and alkylation thereof. More specifically, 2,7-dihydroxyfluorene obtained in cyclization stage is converted into alkali metal salt and toluene solution of 2-diethylaminoethyl chloride is added to preheated aqueous solution of the above salt at molar ratio 1:(3-5), preferably 1:4, to form 2,7-bis[2-(diethylamino)ethoxy]fluorenone, which is then treated with concentrated aqueous hydrochloric acid at molar ratio 1:(3.5-4), preferably 1:3.5.
EFFECT: increased yield and improved quality of product, and simplified process.
3 cl, 3 dwg, 4 ex
FIELD: organic chemistry, chemical technology.
SUBSTANCE: invention relates to a method for synthesis of 3,4'-diamino-4-R-benzophenones of the general formula: wherein R means Cl, Br, F, -CH3, -OCH3,
that are used as intermediate product in synthesis of azo dyes useful for staining protein fibers and possessing the unique indices of thermal stability. Method involves steps for nitration reaction of substituted benzophenones with potassium nitrate in concentrated H2SO4, nucleophilic replacing halogen (wherein R means Cl) in interaction with O- and N-nucleophilic compounds in dimethylsulfoxide (DMSO) medium in the presence of K2CO3 and reduction of 3,4'-dinitro-4-R-benzophenones. The nitration reaction of synthesized benzophenones is carried out at temperature 20oC for 5 h in the mole ratio 4'-nitro-4-R-benzophenone : KNO3 = 1.0:1.15. Nucleophilic replacing halogen is carried out at temperature 40-60oC for 1-5 h in the mole ratio substrate : nucleophilic compound = 1.0:1.05, and reduction of dinitrobenzophenones is carried out with SnCl2 x 2H2O in 18% HCl medium, in the mole ratio 3,4'-dinitro-4-R-benzophenone : SnCl2 x 2H2O = 1:6, at temperature 20oC for 0.15 h. Invention provides decreasing cost of synthesis, reducing time and temperature in carrying out the process, enhancing purity and yield of end products.
EFFECT: improved method of synthesis.
4 tbl, 4 ex
SUBSTANCE: invention relates to a method of continuous production of alkylamino(meth)acrylamide of formula (C) by reacting a formula (B) compound with a formula (A) compound in the presence of a re-esterification catalyst in the presence of at least one polymerisation inhibitor in a continuous re-esterification installation. Reacting substances are continuously fed into the corresponding reactor (1) and the alcohol formed from the reaction is continuously removed in form of an azeotropic mixture of methanol and methyl(meth)acrylate (13) (mixture of ethanol and ethylacrylate 13, respectively) using a distillation column (2). The reaction mixture is constantly fed from the reactor into the distillation column (3) or, respectively, into evaporator (5). Highly volatile components (A, B, methanol or, respectively, ethanol) and a very small part of amide end product (C) are tapped from the head of the column and returned to the reactor. Amide end products (C) together with catalyst and polymerisation inhibitor, as well as heavy by-products are tapped from the bottom of the column. Material flow (15) from the bottom of the distillation column (3) is continuously taken for distillation to obtain pure end product.
EFFECT: improved quality of product, high efficiency and output.
15 cl, 1 tbl, 1 ex, 1 dwg
SUBSTANCE: improved method of producing 2,7-bis[2-(diethylamino)ethoxy]fluoren-9-one dihydrochloride, known as thylorone or amixine, and used as an immunostimulating and antiviral agent, involves treating 2,7-bis[2-(diethylamino)ethoxy]fluoren-9-one in methylene chloride with hydrogen chloride in gaseous state of in form of hydrochloric acid, preferably in molar ratio 2,7-bis[2-(diethylamino)ethoxy]fluoren-9-one : hydrochloric acid equal to 1:2.05-3.0. A solution of 2,7-bis[2-(diethylamino)ethoxy]fluoren-9-one dihydrochloride in methylene chloride is obtained, which is cooled to temperature not below minus 12°C to obtain a suspension and then filtered and dried. The filtered residue is dried in inert gas or air at temperature from 90 to 110°C or in a vacuum, as a rule. Completion of salt formation is usually controlled from increase in temperature of the reaction mass and its stabilisation to a value between 32 and 34°C, as well as from the pH value, which must not be higher than 4.0. The filtered residue is dried in an inert gas or air, at temperature from 90 to 110°C or in a vacuum, as a rule.
EFFECT: simplification of the process due to exclusion of inflammable solvents and obtaining a product of high quality with high output.
6 cl, 1 dwg, 3 ex
SUBSTANCE: invention relates to a method of producing and aminophenol compound of formula (1) , where each of R1 and R2, which can be identical or different, are a hydrogen atom, C1-C6 alkyl group, which can be substituted with phenyl, or phenyl; R1 and R2 together with the neighbouring nitrogen atom can form a 5- or 6-member heterocyclic group, selected from piperidinyl and piperazinyl; the heterocyclic group can be substituted with one substitute selected from hydroxyl group, C1-C6 alkyl group and phenoxy group, which can have a C1-C6 alkoxy group, substituted with 1-3 halogen atoms. The method involves reacting a cyclohexanedione compound of formula (2) with a amine compound of formula (3) , where R1 and R2 assume values given above, in neutral or basic conditions.
EFFECT: wider range of use of the compound.
8 cl, 4 dwg, 13 ex
SUBSTANCE: invention relates to a method for synthesis of 4-(dimethylamino)-1-alkyl-1-methyl-2-alkyn-1-ols of general formula (1): where R=C2H5, C4H9, C6H13, which are substances with physiological activity, particularly cholinolytic properties. The method involves reacting 3-alkyl-3-methyl-1-alkyn-3-ols with N,N,N1,N1-tetramethylmethanediamine in the presence of a copper monochloride catalyst in molar ratio 3-alkyl-3-methyl-1-alkyn-3-ol: N,N,N1,N1-tetramethylmethanediamine: CuCl=10:(10-12):(0.4-0.6) in an argon atmosphere at temperature 50-90°C and atmospheric pressure, predominantly at 80°C, for 3-5 hours. Output of 4-(dimethylamino)-1-alkyl-1-methyl-2-alkyn-1-ols (1) is 84-96%.
EFFECT: method increases output of products.
1 cl, 3 dwg, 1 tbl, 12 ex
SUBSTANCE: invention relates to an improved method of producing 2-[(dimethylamino)methyl]phenol used in the food industry and medicine, as well as lubrication and engine oil additives, corrosion inhibitors for different types of steel, stabilisers of motor car and rocket fuel, monomers, plastic and different types of rubbers. The method involves reacting phenol with N,N,N,N-tetramethylmethylenediamine. The reaction is carried out in the presence of a copper (I) chloride catalyst in molar ratio phenol: N,N,N,N-tetramethylmethylenediamine: CuCl=10:(10-11):(0.2-0.4) at atmospheric pressure, mainly at temperature of 50°C for 3.5-4.5 hours.
EFFECT: increased selectivity of the process and output of the desired product, reduced reaction temperature.
1 cl, 2 dwg, 1 tbl, 1 ex
FIELD: medicine, pharmaceutics.
SUBSTANCE: in the given invention, there is offered a method for preparing a compound of formula , where Y is specified of CH3, CH2OH, CH2CH2OH, CH2Br and Br; involving the stages: (1) reaction of the compound of formula where OX represents hydroxy or O-M+ where M+ represents cation chosen of Li+, Na+ and K+ and Y is such as specified above; with trans-cynnamaldehyde , with a secondary amine compound added; then (2) acid treatment of a product from the previous stage to prepare a compound of formula (I). The aforesaid method can be used for preparing tolterodine and fezoterodine which are effective in treating the hyperactive urinary bladder. There are also declared compounds of formulae V, VI and VII.
EFFECT: development of the effective method for preparing the compound.
25 cl, 19 ex
SUBSTANCE: proposed hydrogen sulphide and/or low-molecular mercaptan remover is in form of amino esters with general formula: (R-)nN(-CH2-O-R')m, where R is alkyl, isoalkyl C1-C14 or cyclohexyl, or benzyl, or a bivalent group with formula - CH2-O-CH2-CH2-, bonded to a nitrogen atom of an amino ester, with formation of five-member heterocyclic ring; R' - alkyl, isoalkyl or alkenyl, preferably C1-C4; n=1 or 2, m=3-n. The invention also pertains to the method of purifying oil, water-oil emulsions, oil products, hydrocarbon gases, stratal water and process liquids from hydrogen sulphide and/or low-molecular mercaptans by treating the starting material using the above described remover. The proposed remover and a composition based on it have higher reaction capacity compared to hydrogen sulphide, light mercaptans and provides for their effective neutralisation in aqueous and non-aqueous media at normal and high temperatures (10-90°C and above). The proposed remover also has bactericidal activity towards sulphate reducing bacteria and anti-corrosion activity in hydrogen sulphide-containing media, and can be used as a bactericide-inhibitor of hydrogen sulphide corrosion in oil-field media.
EFFECT: improved properties of the remover.
4 cl, 9 ex
SUBSTANCE: method includes reacting a compound of formula (II) with a compound of formula (III) in alkaline conditions and in the presence of a sulphite. In formulae I, II and III (*) denotes a chiral centre; R1 is a straight or branched alkyl containing 1-4 carbon atoms; R2 is hydrogen, a straight or branched alkyl containing 1-4 carbon atoms; R3 is a straight or branched alkyl containing 1-6 carbon atoms, an alkoxy, a cycloalkoxy, a phenyl or a substituted phenyl, a heterocyclyl; and R4 is an alkyl, a haloalkyl, an aryl, or a substituted aryl, where the substitute includes oxo, halogen, hydroxy, cyano, nitro, amino, alkylamino, dialkylamino, alkyl, alkoxy, haloalkyl, aryl, heterocyclyl, -NRaRb, -NRaC(=O)Rb, NRaC(=O)NRaRb, -NRaC(=O)ORb, -NRaS(=O)2Rb, -ORa, -C(=O)Ra-C(=O)ORa, -C(=O)NRaRb, -OCH2C(=O)NRaRb, -OC(=O)NRaRb, -SH, -SRa, -SORa, -S(=O)2NRaRb, -S(=O)2Ra, -SRaC(=O)NRaRb, -OS(=O)2Ra and -S(=O)2ORa, where Ra and Rb are identical or different and are independently hydrogen, alkyl, haloalkyl, alkoxy or aryl; the compound of formula (I) and compound of formula (II) are present in an R or S configuration of a racemic mixture. The molar ratio of the sulphite to the compound of formula (II) is (0.8-2.5):1 and the molar ratio of the compound of formula (III) to the compound of formula (II) is (1.1-5.0):1.
EFFECT: method is suitable for extensive industrial production and enables to obtain a product with high output.
18 cl, 3 tbl, 20 ex
SUBSTANCE: invention relates to new derivatives of trans-2-decenoic acid in formula (1′), or pharmaceutically acceptable salts thereof, in which values for groups Y′, W′ are defined in the formula of invention. Invention also relates to a pharmaceutical agent, having activity as neurotrophic factor, and/or easing effect on a side effect caused by introduction of anticancer agents containing derivative of trans-2-decenoic acid in formula (1), or its pharmaceutically acceptable salt as an active ingredient, in which values for groups Y and W are defined in the formula of invention.
EFFECT: pharmaceutical agent has a sufficiently wide range of application, such as a preventive or therapeutic agent for dementia, Alzheimer's disease, Parkinson's disease, depression and so on, medical or reducing agent for spinal injury or relieving agent for side effect caused by introduction of anticancer agents.
23 cl, 9 dwg, 68 ex, 2 ex
SUBSTANCE: invention relates to an improved method of producing 2-(2-tret.-butylamino-ethoxy)-ethanol (tret.-butylaminodiglycol). Product is used, for example, gas scrubbing, for the selective separation of acidic gases, for example H2S from gas streams which comprise mixtures of one or more acidic gases and CO2. Method of producing 2-(2-tret.-butylamino-ethoxy)-ethanol is realised by reacting diethylene glycol with tret.-butylamine in molar ratio tret.-butylamine and diethylene glycol from 1 to 4, in presence of hydrogen and catalyst containing copper oxide or aluminium oxide at temperature of 160-220 °C and absolute pressure from 1 to 200 bar to degree of conversion of diethylene glycol in range from 20 to 80. Process can be carried out in gas phase in molar ratio of hydrogen to diethylene glycol from 40 to 220 or in mixed gas-liquid phase at in molar ratio of hydrogen to diethylene glycol from 5 to 50. Catalytically active mass of catalyst before its reduction with hydrogen contains from 20 to 75 wt% of aluminium oxide (Al2O3) and from 20 to 75 wt% oxygen-containing compounds of copper, designed for CuO. Preferably catalytically active mass of catalyst before its reduction with hydrogen contains from 25 to 65 wt% of aluminium oxide (Al2O3) and from 30 to 70 wt% oxygen-containing compounds of copper, designed for CuO. Reaction can be performed isothermally, with temperature deviation of not more than ±8°C. Catalyst can be placed in a reactor in form of a fixed bed. Catalyst can have micropore volume < 0.5 cm3/g. In catalyst at normalisation pores can have size of > 0 to ≤ 20 nm, ≤ 30 % of pores have size of up to 5 nm and more than 70% of pores have a size of > 5 to 20. Unreacted diethylene glycol and/or tret.-butylamine is returned to reaction.
EFFECT: method enables to obtain products with high conversion, selectivity and output.
13 cl, 3 tbl, 16 ex
SUBSTANCE: composition for application as excipient in pesticide-containing mixtures for spraying contains pesticide and alkoxylate, where alkoxylate is an amine-alkoxylate (A)
where R1 and R2 independently represent ethylene, propylene, butylene, or their mixture, R6 represents H, C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, -SO3Ra-P(O)ORbORc, -CH2CO2Rd or -C(O)Re, Ra and Rd independently represent H, inorganic or organic cations, Rb and Rc independently represent H, inorganic or organic cations, C1-C6-alkyl, C2-C6-alkenyl or C2-C6-alkynyl, Re is C1-C22-alkyl, C2-C22-alkenyl, C2-C22-alkynyl, C6-C22-aryl or C7-C22-alkylaryl, n and m independently have a value of 1 to 30.
EFFECT: increased efficiency.
12 cl, 3 tbl, 5 ex