Method for producing 1,2-bis(2-aminoethoxy)benzene
(57) Abstract:The invention relates to the production of intermediates for macroheterocyclic compounds visa and sacroiliac. The way passes through a three-stage scheme, including: 1) receiving-2-chloroethylamide of N-acetylethanolamine and chloride tiomila when heated in the environment, benzene, toluene or chloroform; 2) alkylation of pyrocatechin N-2-chloroethylamide when the molar ratio of reactants is 1: 2 in n-butyl alcohol in the presence of sodium hydroxide and a catalytic amount of energy balances; 3) the hydrolysis of 1,2-bis (N-2-acetylbenzoate)-benzene aqueous solution of sodium hydroxide under heating, followed by extraction with n-butyl alcohol, 1,2-bis(2-aminoethoxy)benzene and distillation of the solvent. The proposed method can simplify the process by using commercial available reagents, as well as to increase the yield of the target product. table 1. The invention relates to an improved process for the preparation of 1,2-bis(2-aminoethoxy)benzene, which finds application in the synthesis of Aza - and discrimnation.The known method for producing 1,2-bis(2-aminoethoxy)benzene in two ways  . According to the first ditosylate 1,2-bis(2-guide the Ute hydrazine hydrate in ethanol. The second option ditosylate 1,2-bis(2-hydroxyethoxy)benzene miniroot sodium azide for 24 hours. Then designee derived restore with lithium aluminum hydride in ether for 24 hours prior to 1,2-bis(2-aminoethoxy)benzene.The full scheme of the synthesis according to the method should also include the stage of producing 1,2-bis(2-hydroxyethoxy)benzene and its ditosylate, as they are not industrial, and, therefore, it should consist of four stages.The disadvantages of this method is the use of scarce they are flammable and explosive, toxic chemicals: hydrazine hydrate, sodium azide, lithium aluminum hydride, ether, and significant duration of individual stages.The essence of the proposed method is to simplify the process technology, the use of commercial available reagents, the increase in the yield of 1,2-bis(2-aminoethoxy)benzene, which is achieved by obtaining 1,2-bis(2-aminoethoxy)benzene by alkylation of pyrocatechin in butanol N-2-chloroethylamide with subsequent hydrolysis of 1,2-bis(2-acetylbenzoate)benzene solution of sodium hydroxide. Required for stage alkylation of N-2-chlorotoluene obtained from N-acetylethanolamine the action of chloride It is that obtain 1,2-bis(2-aminoethoxy)benzene is carried out with the 3-stage scheme, instead of the known 4-stage, using less scarce and safer chemicals. The yield of the target compound with regard to fewer stages higher than in the known method.The invention is illustrated by examples 1-3.Example 1. Obtaining N-2-chloroethylamide.In a three-neck flask equipped with a mechanical stirrer, thermometer and addition funnel is placed 103,1 g (1 mol) of N-acetylethanolamine and 200 ml of benzene. Then the mixture with vigorous stirring cooled in an ice bath to 10oC and added from a dropping funnel 119 g (1 mol) of chloride tiomila with such speed that the temperature of the reaction mixture did not exceed 30oC. By the addition of about one-third of the total number of chloride tiomila reaction mass is much thickens, and with the further addition of the reagent is gradually diluted. After the addition of all chloride tiomila the reaction mixture was stirred for 2 h at room temperature and left overnight.After exposure to the reaction flask is connected downstream of the fridge and distilled benzene, first under normal pressure, and the East is a career. The residue is a dark thick oil is transferred into a flask of Clausena and vacuum distilled at 110-112oC and 2-3 mm RT.article allocate and 91.2 g of N-2-chloroethylamide. Yield 75%, n2D01,4770,d2401,778; MRD: calc. 29,15; calc. 29,16. The infrared spectrum, in Basel. oil, cm-1: 3300 (N-H), 1630 (amide I band), 1540 (amide II band), 650 (C-CI).Literature data : I. instrumentation. 135-136 (10); n2D01,4894.
Example 2. Obtain 1,2-bis(N-2-acetylbenzoate)benzene
In a three-neck flask equipped with a mechanical stirrer, addition funnel, reflux condenser and a tube for entry of inert gas, put 22,0 g (0.2 mol) of pyrocatechin, 16,8 g (0.42 mol) of powdery sodium hydroxide, 3 g of TEB and 300 ml of n-butyl alcohol. The reaction mixture is boiled under nitrogen atmosphere with stirring for one hour. Then added dropwise over 1.5 hours to 48.6 (0.4 mol) of N-2-chloroethylamide, after which the reaction mixture is boiled under stirring for 4 hours. Next, the contents of the flask are cooled to room temperature and filtered. From the filtrate butyl alcohol is distilled off in vacuum (20-30 mm RT.CT.) and the residue is subjected to vacuum distillation. Get 42,0 g of 1,2-bis(N-2-acetylbenzoate)benzene with so Kip. 140-146oC when the KTR, in chloroform, cm-1: 3300 (N-H), 1660 (amide I band), 1515 (amide II band). PMR-spectrum , M. D.: 6,99 (4H, o-C6H4), 6,20 (2NH), 4.09 to t (hon2), 3,52 (HSN2NH), 1,98 (HSN3).Example 3. Obtain 1,2-bis(2-aminoethoxy)benzene.In odnogolosy flask, equipped with reflux condenser, place of 8.4 g (0.03 mol) of 1,2-bis(N-2-acetylbenzoate)benzene, 15 ml of water and 2.8 g (0.07 mol) of aqueous 40% sodium hydroxide solution. The mixture is boiled on a water bath for 2-3 hours before until a drop of the reaction mixture introduced into dilute hydrochloric acid will not dissolve without residue. Then the reaction mixture is cooled to room temperature and extracted with 100 ml of n-butyl alcohol. Butanolic the extract washed with water and dried over potash. After distillation alcohol at 20-30 mm RT.article gain of 5.3 g of 1,2-bis(2-aminoethoxy)benzene. Output 90,1%. Viscous brown oil. PMR-spectrum , M. D.: 7,01 (4H, o-C6H4), 4,10 t (4 N, hon2), 3,53 (4H, HSN2NH2).Literature data : neperedavaemaa oil.The obtained results are illustrated by table data.The compounds characterized by IR and PMR spectra.Thus, prelauncher the number of stages and time costs, to use less scarce and more secure reagents, which greatly simplifies hardware design process, reduces fire hazard.The developed method can be applied both in the laboratory preparative practice, and in industrial production.Sources of information:
1. L. S. Hodgkinson, V. R. Johnson, S. J. Leigh et al. Formation of Complexes between Aza Derivates of Crown Ethers and Primary Alkylammonium Salts. Part 4. Diaza - 18 - crown - G Derivates. J. C. S. Perkin 1, 1979, 2193-2202.2. Heyns, K., Bebenburg W. D. Die Umlagerung von N-Nitroso-N-alkylacylamiden. B. 595 , h. 1, 55-65. Method for producing 1,2-bis(2-aminoethoxy)-benzene, characterized in that pyrocatechin subjected to interaction with N-2-chloroethylamide in the environment of n-butyl alcohol in the presence of base, followed by hydrolysis of the obtained 1,2-bis(N-2-acetyl-aminoethoxy)-benzene aqueous solution of sodium hydroxide.
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
FIELD: special methods in organic synthesis.
SUBSTANCE: known drug: racemic 1-(isopropylamino)-3-(1-naphthyloxy)-2-propanol, briefly called propranolol, is converted into propranolol hydrofluoride, which is dissolved in ethanol at 55-70оС to form concentrated solution. The latter is gradually cooled to 20-26оС, after which is added seed of one of enantiomers, solution is stirred for 30-60 min, filtered non-racemic propranolol hydrofluoride enantiomer having the same configuration as the seed previously added. Racemic compound is added to mother liquor in amount compensating separated precipitate, mother liquor is heated at 55-70оС to entirely dissolve added material and seed of the other enantiomer is added. Subsequent crystallization gives precipitate rich in the other enantiomer and process is several times repeated. Enantiomer purity is then raised by recrystallization. Non-racemic propranolol salts are finally converted into free propranolol enantiomers. Method of invention can be used in pharmaceutical practice.
EFFECT: enabled involvement method-assisted preparation of non-racemic propranolol.
FIELD: medicine, pharmaceutics.
SUBSTANCE: device refers to new styrene derivatives with the structure formula A in the form of geometrical isomers or tautomers and their pharmaceutical acceptable salts. In structural formula (A) R1 represents hydrogen; R2 represents hydrogen or C1-C6alkyl; R3, R4, R5 and R6 are identical or different and independently represent hydrogen, halogen, C1-C6alkyl or -OR12; R7 represents hydrogen or C1-C6alkyl; R8 represents hydrogen; R9 represents hydrogen, C1-C6alkyl, or -C(=O)R13; R10 represents hydrogen or C1-C6alkyl; Z represents W-Y, wherein W represents -C(R14)(R15)-; Y represents -C(R16)(R17)-; each R12 independently represents hydrogen or C1-C6alkyl; each R13 independently represents C1-C6alkyl; R14 and R15 are identical or different, and independently specified in hydrogen, fluoro, methyl, ethyl, trifluoromethyl, -OH, -OCH3 or -NH2; or R14 and R15 together form oxo; R16 and R17 are identical or different and independently represent hydrogen, halogen, C1-C6alkyl or -OR12. The other radical values are specified in the patent claim.
EFFECT: compounds may be used for treating an ophthalmic disease or disorder in an individual which can represent age-related macular degeneration or Stargardt macular degeneration.
17 cl, 14 tbl, 143 ex