WO2013048280A1 - Method for the selective production of n-methyl-para-phenetidine - Google Patents

Abstract

The invention entitled "Method for the selective production of N-methyl-para-phenetidine" relates to chemical technology processes and, more specifically, to methods for the catalytic alkylation of aromatic amines and nitro compounds. The invention concerns a method for producing N-methyl-para-phenetidine (N-methyl-para-ethoxyaniline; N-methyl-para-aminophenetole) from para-phenetidine (para-aminophenetole; para-ethoxyaniline) or para-nitrophenetole (1-ethoxy-4-nitrobenzene) and methanol in the presence or absence of hydrogen over a heterogeneous catalyst. The proposed method makes it possible to exploit existing industrial plants used for producing aniline and N-methylaniline. The aim of the invention is to make it possible to produce N-methyl-para-phenetidine with a purity of not less than 98% and a high yield, thus permitting cost-effective, multi-tonne manufacture.

Description

 A method for the selective preparation of Ν-methyl-para-phenethidine.

The invention relates to chemical-technological processes, and in particular to methods for catalytic alkylation of aromatic amines and nitro compounds.

 The invention relates to a method for producing Ν-methyl-para-phenethidine (Ν-methyl-para-ethoxyaniline; Ν-methyl-para-aminophenetole) from para-phenetidine (para-aminophenetole; para-ethoxyaniline) or para-nitrophenetole (1-ethoxy- 4-nitrobenzene) and methanol in the presence of hydrogen or without hydrogen on a heterogeneous catalyst.

 The proposed method allows the use of existing industrial plants used to obtain aniline and N-methylaniline.

 Ν-methyl-para-phenethidine is currently used as an antiknock additive or additive to motor fuel [US Pat. 2 309 943, Russian Federation, IPC С07С217 / 82, С07С235 / 24, C10L1 / 223, C10L1 / 224. The use of derivatives of para-ethoxyanilines that increase the resistance of hydrocarbon fuels to detonation, and the fuel composition (options) / Ivanov Yu. A., Frolov A. Yu. Et al. - JVO 2006108236/04, decl. 03/16/2006, publ. 10.1 1.2007, bull. W 31].

Given the unique properties of Ν-methyl-para-phenethidine, which is a simple, mixed ether, its use as additives, additives to gasolines is very promising and is limited only by the lack of industrial production. In this regard, the development of an economical industrial method for producing Ν-methyl-para-phenethidine is a very urgent task.

 A known method of producing Ν-methyl-para-phenethidine [US Pat. 2 309 943, Russian Federation, IPC С07С217 / 82, С07С235 / 24, C10L1 / 223, C10L1 / 224. The use of derivatives of para-ethoxyanilines, which increase the resistance of hydrocarbon fuels to detonation, and the fuel composition (options) / Ivanov Yu. A., Frolov A. Yu. Et al. - Jfe 2006108236/04, published March 16, 2006, publ. 10.1 1.2007, B WI.N ° 31], which provides reliable evidence that Ν-methyl-para-phenethidine is actually obtained, its physico-chemical and spectral studies confirming its structure. In this work, N-methyl-para-phenethidine was obtained in two ways: from -methyl-Y-acetyl-para-phenethidine by boiling with sulfuric acid, adding sodium hydroxide and subsequent extraction with toluene, as well as according to the procedure described in [Weigant Hilgetag. Experimental Methods in Organic Chemistry.-Moscow: Chemistry, 1964.- 944 s], using dimethyl sulfate, sodium bicarbonate, sodium hydroxide or potassium with a yield of 50% of theoretical. However, these production methods are preparatory in nature and unacceptable for the production of Ν-methyl-para-phenethidine under conditions of large-tonnage production.

An analysis of the periodical and patent literature revealed only one copyright certificate [A.S. 166035 USSR, IPC С07с. The method of obtaining Ν-alkyl-P-phenethidines / L.A. Skripko (USSR). - L 805091 / 23-4; declared 29.1 1.1962; publ. 11/10/1964, Bull. N ° 21 -2s], which proposes a method for the alkylation of p-phenetidine with aliphatic alcohols. In accordance with this copyright certificate, alkylation was carried out at the boil of a solution of p-phenetidine in aliphatic alcohol, with a reflux condenser, on Raney nickel. The temperature of the process was determined by the boiling point of a solution of paraphenetidine in a specific aliphatic alcohol. In this way, N-amyl-para-phenethidine, Ν-decyl-para-phenethidine, N-cyclohexyl-para-phenethidine were obtained. The yield of target products was 85-95% of theoretical.

These are good results, but it should be noted that the obtained indicators can be greatly overestimated. The fact is that the yield of N-alkylated products in this copyright certificate was determined by the results of a simple distillation of the catalyst, which does not make it possible to isolate pure Ν-alkylphenetidines.

For a complete objective assessment of the method, there is also not enough data on the duration of the catalyst (the number of repetitions of experiments on one catalyst load), and without this, the consumption of catalyst is unacceptably large.

The main disadvantage of the method, which crosses out the possibility of using it for our purposes, is that the solution of paraphenetidine in methanol boils at a temperature below 100 ^° C, at which methanol dehydrogenation practically does not occur and, accordingly, methylation does not occur. The lack of information on the Ν-methylation of paraphenetidine led us to pay attention to the methods for the preparation of Ν-alkylated anilines, which are close in structure to our facility, for which there is enough information. Moreover, we understood that the nucleophilicity of nitrogen in para-phenethidine is much higher than in aniline and, accordingly, para-phenetidine should have a higher reactivity to Ν-alkylation and to Ν, ди-dialkylation. This fact imposes certain restrictions on the possibility of transferring the data obtained with Ν-alkylated aniline to the synthesis of Ν-methyl-para-phenethidine. The second limitation is the ethereal nature of para-phenetidine, which does not allow the use of Ν-alkylation methods, leading to hydrolysis of the ester.

Given these limitations, the following materials were examined on methods for producing Ν-alkylated aromatic amines.

A known method of gas-phase alkylation of aniline with alcohols on an aluminosilicate catalyst, on which 2-5% nickel oxide is deposited at a temperature of 200-250 ° C by jointly passing aniline vapor and alcohol, usually taken in 3-4 times excess, through the catalyst, with the release of the reaction product . The yield of a mixture of mono- and dialkylanilines is 95-98%. Derivatives of isopropyl, isobutyl, butyl, and nanyl alcohols were obtained. [A.S. 666167 USSR, С07с 85/06, С07с 87/50, А01 Ν5 / 00. The method of obtaining Ν-alkylanilines / G.V. Yesipov, A.V. Yazlovitsky, N.A. Onishchenko, I.E. Kishkovskaya (USSR). - D 2484138 / 23-04; declared 05/10/1977; publ. 06/05/1979, Bull. JV "21-ZS]

 Since it is indicated that the method does not allow the reaction to shift toward monoalkylanilines, it is unacceptable for us, since if it is used to produce Ν-methyl-para-phenethidine, the situation will only worsen. In addition, the catalyst used in the method has an acidic character, which can contribute to the hydrolysis of the ether group of para-phenetidine.

 A known method for the joint production of aniline and N-methylaniline from nitrobenzene, methanol and hydrogen in the gas phase on a heterogeneous copper-chromium industrial catalyst of the NTK series, to produce aniline and Ν-methylaniline. The yield of N-methylaniline and aniline in terms of nitrobenzene is 95%. [Pat. 2135460, Russian Federation, IPC6 C07C209 / 36, C07C209 / 16, C07C21 1/46, C07C21 1/48. Joint production of aniline and Ν-methylaniline / Batrin Yu.D., Nikolaev Yu.T. et al. - 97120738/04, claimed. December 16, 1997, publ. 08/27/1999].

This is an interesting method for us, allowing us to use cheaper raw materials to obtain the target product. However, it has a significant drawback - high thermal loads in the frontal layer of the catalyst, which leads to the destruction of the catalyst and significantly narrows the range of possible catalysts for the process. In addition, in relation to our task, high temperatures can contribute to the hydrolysis of the ether group of para-phenetidine and Ν-methyl-para-phenetidine. These disadvantages are common to all production methods in which alkylated raw materials are aromatic nitro compounds. A common disadvantage is also the increased content of tertiary amine impurities, especially in the initial period of contacting.

Known is an improved method for producing Ν-methyl-substituted aromatic amines by reducing the corresponding nitro compounds with methanol in the vapor phase at elevated temperature in the presence of an industrial copper-containing catalyst of the brand "Virgon", or "C-40", or ΉΤΚ-10-7Φ ", modified with nickel or palladium , or platinum, taken in an amount of 0.3-10 May.%. The process is usually carried out at a temperature of 200-260 ° C, atmospheric pressure and the feed rate of the liquid initial mixture of methanol with an aromatic nitro compound from 0.5 to 2.5 hours ^"1 under keeping the ratio of methane l / aromatic nitro compound in the initial mixture from 1: 1 to 5: 1. The total yield of aromatic amines is up to 99.5%, product productivity is up to 0.4-1.3 g / g h. The method allows, depending from the ratio of reagents used, change the ratio of the resulting N-methyl-substituted and unsubstituted aromatic amines [US Pat. 2207335, Russian Federation, IPC ⁷ С07С211 / 48, С07С21 1/46, С07С209 / 36. A method of producing aromatic amines by reduction of the corresponding nitro compounds / Vinokurov V.A., Stytsenko V.D. et al., JSTs 2001111547/04, claimed 04/28/2001, publ. 06/27/2003].

The disadvantage of this method, in addition to those listed above in the previous method, is the use of an expensive catalyst modified with platinum group metals, which may be It is justified only by the increased life of its service, which is not indicated in the patent.

Known is an improved method for producing Ν-methylaniline by alkylation of nitrobenzene with formaldehyde or a mixture thereof with methanol on copper oxide-containing catalysts at 220-260 ° C. The molar ratio of nitrobenzene: alkylating agent is usually 1: (2.5-6.0), and the optimal molar ratio of formaldehyde to methanol in the alkylating agent is 1: 1, and formaldehyde can be used in the form of its aqueous solution in the presence of hydrogen with a molar the ratio of nitrobenzene to hydrogen 1: (3, 0-6.0) on copper oxide catalysts promoted with oxides of manganese, chromium, iron and cobalt, on a carrier - alumina. The proposed method allows for the conversion of nitrobenzene to 100% and the yield of the target product - N-methylaniline 80-88%, to simplify and reduce the cost of technology, reduce energy consumption. [Pat. 2240308, Russian Federation, IPC ⁷ С07С211 / 48, С07С209 / 26. The method of obtaining Ν-methylaniline / Gorbunov B.N., Slepov S.K. et al., L 2003106495/04, claimed. 03/07/2003, publ. 20.1 1.2004].

 A significant drawback of the method is the use of an aqueous solution of formaldehyde, which necessitates the disposal of a large amount of additional water, which inevitably increases the cost of production, as well as the propensity of formaldehyde to polymerize.

Known is an improved method for producing Ν-methylaniline from nitrobenzene, methanol and hydrogen in the gas phase on a copper-containing catalyst comprising zinc and chromium compounds. The process is carried out in two stages in two series-connected contact devices, in each of which nitrobenzene and methanol are supplied in a mixture or separately: nitrobenzene - to the first device, and methanol - to the second device, using layer-by-layer catalyst loading with the first contact device the creation of a "frontal layer", the temperature in which should not exceed 350 ° C, a volume of 10-50% of the total catalyst used in this contact apparatus, the following composition: copper oxide May 37-40. %, chromium oxide May 18-20. %, zinc oxide May 20. %, aluminum oxide - the rest, or in both contact devices as a copper-containing catalyst using a catalyst composition: copper oxide May 21.4-26.4. %, chromium oxide 3.4-5.8 May. %, alumina May 3.3-22.3. %, double chromite of copper and zinc of the empirical formula ZnxCuyCr204, where x = 0.8-10, y = 0.4-0.9, 54.5-71.9 May. % [Pat. 2263107, Russian Federation MPK7S07S21 1/48, S07S209 / 26. Two-stage method for producing Ν-methylaniline / Gorbunov B.N., Utrobin A.N. et al., N_> 2003131054/04, claimed 10/22/2003, publ. 10/27/2005]. The main disadvantage is that it is difficult to coordinate the operation of two reactors having different capacities and, moreover, changing during operation.

A known method of producing Ν-methylaniline by reductive alkylation of nitrobenzene or its mixture with aniline methanol in the gas phase on an oxide copper-chromium catalyst. In this case, reductive alkylation is carried out in medium of a mixture of hydrogen and carbon dioxide, taken in a molar ratio of about 3: 1, obtained by gas-phase condensation of methanol with water. A mixture of hydrogen and carbon dioxide obtained in a separate contact apparatus is directed to reductive alkylation. [Pat. 2275353, Russian Federation IPC S07C209 / 36, S07C211 / 48. The method of obtaining Ν-methylaniline / Gorbunov B.N., Slepov S.K. et al., Jfe 2004107764/04, claimed. 03/15/2004, publ. 04/27/2006]. The disadvantage is the complexity of the catalytic installation without obvious positive points. The period of run of the catalyst prior to discharge is unknown.

 An improved method for producing Ν-methylaniline by reductive ительным-alkylation of aniline is known. The proposed method is carried out at elevated temperature, usually at a temperature of 180-280 ° C, on copper-containing catalysts with a copper content in terms of copper oxide of 9-60 wt.%, Including the recovery of the catalyst at a temperature of 180-200 ° C and the subsequent isolation of the target product from catalysis by distillation. The process is carried out in an environment of exhaust gases, instead of hydrogen, they also restore the catalyst. [Pat. 2270187, Russian Federation IPC С07С209 / 36, С07С21 1/48. The method of obtaining Ν-methylaniline / B.A. Golovachev, V.N. Dogadaev. - j b 200411 1480/04, declared. 04/14/2004, publ. 02/20/2006]. As in the previous method, the lifetime of the catalyst is completely unclear.

Known liquid-phase catalytic method for producing alkyl aniline. Aniline alkylation is carried out with formalin at aniline: formalin ratio = 1.6 / 1, 1 in the presence of hydrogen and a fixed palladium catalyst in ethyl or methyl alcohol at a temperature of 55-65 ° C and a pressure of 0.2-0.4 MPa. The process is carried out in a cylindrical reactor mounted on a rocking chair with a swing number of 120-160 min ^"1 , in the middle part of which a porous block cellular palladium catalyst is placed, the active layer of which is modified by palladium nanoparticles, with a porosity of 70-95% and a palladium content of 1.8- 3.7%. In this case, hydrogen is supplied through the fitting of the reactor cover. The method allows to reduce energy consumption and to reduce the proportion of by-products. [Pat. 2270831, Russian Federation IPC S07C211 / 48, C07C209 / 26, B01J23 / 44, B01J35 / 04. catalytic alkylation of aniline / A. A. Revina, A. I. Kozlov, et al. - Jfs 2004133550/04, declared 18.1 1.2004, published 27.02.2006]. Disadvantages - it is impossible to ensure the selectivity of the process with respect to monomethylaniline. For this reason, trying at least as to increase selectivity, the process is carried out with a lack of formalin, with aniline: formalin ratio of 1.6: 1.1, a very expensive catalyst, which makes the method completely unsuitable for industrial use.

Known liquid-phase catalytic method for the alkylation of aromatic amines. The method includes the alkylation of aromatic amines in the presence of hydrogen and lower alcohols at a temperature of 50-70 ° C on a heterogeneous catalyst. A distinctive feature of the method is the alkylation of amines with formalin in a reactor with a reaction zone filled with a catalyst consisting of a block of highly porous cellular support based on alumina with a porosity of at least 70-95% and the active component is palladium with a mass content of 1.3-2%. The method allows mainly to obtain monomethylaniline, to reduce the content of the active component - palladium in the catalyst, and also to reduce the reaction pressure and hydraulic resistance of the catalyst layer. [Pat. 2285691, Russian Federation IPC С07С21 1/48, С07С209 / 26, B01J21 / 04, B01J23 / 44, B01J35 / 04. The method of liquid-phase catalytic alkylation of aromatic amines / A.I. Kozlov., V.N. Grunsky, A.V. Bespalov. - JVI 20051 12854/04, claimed 04/28/2005, publ. 10/20/2006]. The disadvantages of the described method are the same as in the previous method.

Known is an improved method for producing aniline and N-methylaniline by gas-phase catalytic reduction of nitrobenzene with aqueous solutions of methanol or formaldehyde. Upon receipt of aniline and Ν-methylaniline, the reduction is carried out with an aqueous solution of methanol with a concentration of 60-80 wt.% At a molar ratio of nitrobenzene and methanol equal to 1: 1.1-3.5. [Pat. 2259350, Russian Federation IPC ⁷ С07С21 1/48, С07С21 1/46, С07С209 / 26, С07С209 / 36. A method of producing aniline and / or Ν-methylaniline and a catalyst for it / B.N. Gorbunov, S.K. Slepov. -JYO 2003121732/04, stated 07/14/2003, publ. 02/27/2005]. The disadvantage is a large additional amount of contaminated water sent for disposal, which significantly worsens the economic performance of the process.

A known method of producing Ν-methylaniline by catalytic hydrogenation of nitrobenzene with hydrogen in the presence of methanol on copper-chromium catalyst. The process is carried out sequentially in two reaction zones at 160-200 ° C in the first zone until nitrobenzene is completely converted and 210-240 ° C in the second zone to aniline conversion of at least 93% with a molar ratio of nitrobenzene: methanol: hydrogen 1 :( 2-4) :( 4-10). The method allows to obtain the target product with a yield of more than 92%. [Pat. 2223258, Russian Federation IPC ⁷ С07С21 1/48, С07С209 / 36. The method of obtaining Ν-methylaniline / Yu.D. Batrin, M.K. Starovoitov et al. -JYS! 2003100842/04, claimed 01/15/2003, publ. 02/10/2004].

 This paper does not describe how in the first zone, where the frontal layer effect is realized, it is possible to maintain a temperature of 160-200 ° С. This is possible only at very low nitrobenzene loads, with a low reactor productivity, which has no practical value.

Known two-stage process for preparing Ν-methylaniline Ν-vapor phase catalytic alkylation of aniline with methanol: the first stage is fed aniline and methanol in a molar ratio of 1: 2, and the process is carried out at a temperature of 230-260 ° C and the contact load of 0.7-0.9 h ^{" 1} to the degree of conversion of aniline to Ν-methylaniline 85-95%, the catalate is fed to the second stage (doalkylation) and the process is carried out at 220-240 ° C until the conversion of aniline to Ν-methylaniline is more than 98%, using catalysts based on both stages metal oxides promoted by metal oxides from the group including manganese, iron, chromium, nickel, cobalt Technical result: production of catalysis with a mass fraction of N- methylaniline in the oil fraction of more than 98%, which makes it possible to isolate a marketable product according to a simplified rectification scheme; reduction of energy consumption, lengthening the life of the catalyst. [Pat. 2232749, Russian Federation IPC ⁷ С07С211 / 48, С07С209 / 18. A two-stage method for producing Ν-methylaniline / N.A. Mitin, S.K. Slepov et al. -J4 <2002121792/04, claimed 08/07/2002, publ. July 20, 2004].

 In this patent, as in the previous one, the technical problem is solved for the selective production of a secondary amine in the complete conversion of the feedstock. It is solved the same way, by breaking down the reactor into two zones, and the temperature conditions in the second zone practically coincide in both patents. As for the first zone, here the temperature is the exact opposite, as well as the load. In principle, this problem in one way or another (selection of a catalyst, selection of modes, etc.) is solved in any of the considered methods for the preparation of Ν-alkylated arylamines and, apparently, a zone approach is also possible.

 A known method of producing Ν-alkylanilines from derivatives of aniline and alcohol of the General formula

in _{r nc}

where Rj is a radical selected from H, CH3, C2H5, R.2 is a radical selected from H, _CH3, C2H5, R-h is H or a radical CH _3, C ₂ H ₅ on the catalyst STC series at a temperature of 230-270 ° C, characterized in that, in order to save energy, add to the initial reaction mixture

SUBSTITUTE SHEET (RULE 26) the required amount of nitrobenzene or its derivative corresponding to the resulting alkylaniline, of the general formula

wherein R3 is H or a CH radical, C ₂ H _5, whereby the required reactor temperature is maintained. [Application 2002130524, Russian Federation, IPC ⁷ C07C21 1/48, C07C209 / 60. The method of obtaining Ν-alkylanilines / T.V. Rudakova, A.F. Kachegin et al. - Ш 2002130524/04, decl. 11/14/2002, publ. January 27, 2005]. In this way, it is possible to maintain the temperature only in the frontal layer of the catalyst, and not throughout the reactor.

A known method of producing Ν-methylaniline from nitrobenzene and methanol on an NTK series catalyst at atmospheric pressure and a temperature of 230-270 ° C, characterized in that methanol is used as a hydrogen source for nitrobenzene reduction at a molar ratio of nitrobenzene: methanol 1: 4-10. [Application 2003100063, Russian Federation, IPC ⁷ C07C21 1/48, C07C209 / 18. The method of obtaining Ν-methylaniline / N.G. Belyakov, N.I. Vavilov et al. - 2003100063/04, declared 01/09/2003, publ. 07/10/2004].

 In all methods of alkylating arylamines with alcohols without using hydrogen, excess alcohol becomes the source of hydrogen.

 A known method of producing Ν-methylaniline from nitrobenzene methanol and hydrogen in the gas phase at a coolant temperature

SUBSTITUTE SHEET (RULE 26) 170-300 ° C and a catalyst temperature of 350-450 ° C in a two-stage reactor by catalytic reduction of nitrobenzene, followed by alkylation of aniline with methanol without isolation of aniline in its commercial form at atmospheric pressure on a copper oxide catalyst, including zinc and chromium compounds. This method is characterized in that the process is carried out in a two-stage reactor, the second stage of which is a cavity adiabatic contact apparatus filled with a granular catalyst. [Application 2004104170, Russian Federation, IPC7 C07C211 / 48. The method of obtaining N-methylaniline / Yu.T. Nikolaev, N.G. Belyakov. - JVfe 2004104170/04, stated 02.16.2004, publ. July 27, 2005]. Disadvantages - a very high temperature in the frontal layer of the catalyst will inevitably lead to the destruction of the ether group of para-nitrophenetole, para-phenetidine and Ν-methyl-para-phenetidine; the frontal layer catalyst in this method is acidic, which should further enhance the destruction process.

A known catalytic method for the production of secondary cyclic amines by reacting the corresponding primary cyclic amine with low boiling alcohols. This method consists in carrying out reactions in the presence of a catalytic mixture of metallic copper, aluminum oxide and other metal oxides, in connection with which, cyclic amines can be produced cost-effectively. This invention is proposed for the production of Ν-methylaniline from aniline and methanol using a stoichiometric excess of alcohol, which greatly increases the conversion of aniline to Ν-methylaniline and completely inhibits the formation of Ν, Ν-dimethylaniline. As a result, a sufficiently pure product is obtained by applying distillation to remove unreacted alcohol and water formed during the reaction. The inter-regeneration run of the catalyst is 250 hours. [Pat. 2580284, USA. The production of secondary aromatic amines / Thomas Jay Deal and others - publ. 12/25/1951]. The catalyst contains a large amount of acidic aluminum oxide; therefore, when using this method to obtain метил-methyl-para-phenethidine, hydrolysis of the ester group is very likely.

 A known method for the production of secondary alkylaromatic amines by direct alkylation of primary aromatic amines with primary aliphatic alcohols. The purity of the resulting secondary amines is achieved by the use of distillation or crystallization from an appropriate solution. When using unbranched aliphatic alcohols as an alkylating agent, the yield of the target product reaches from 70 to 90%, while when using branched aliphatic alcohols, the yield of the target product is 40-50%. Raney nickel is used as an alkylation catalyst. [Pat. 2813124, USA. The preparation of secondary aromatic amines / Rip Ji Rayet and others - publ. 12.1 1.1957]. The disadvantage is the low yield of the secondary amine.

A known method for the production of Ν-methylaniline by reacting aniline with methanol in the liquid phase at a temperature of 150-300 ° C, at a methanol pressure of from 30 to 200 atm. AT the presence of a catalyst consisting of copper and chromium and the corresponding formula: Cr ^» Me ^» Me, where Me is Cu, Zn, Fe OR Ni, Me is Ba, Ca, Mg OR Mn, Cr. The metal content in the catalyst: Cr from 20 to 80% of the mass, Me ¹ from 20 to 80% of the mass, Me2 from 0 to 5% of the mass. The yield of Ν-methylaniline is 95%. [Pat. 3819709, USA. The synthesis of Ν-methylaniline / Koichi Murai and others - publ. 06/25/1974]. The disadvantage is the very high pressure during the process.

There are also many materials on the use of catalysts. [A.S. 644526 USSR, 01J 23/76, 01J 21/06, C 07B 27/00. The catalyst for the alkylation of aromatic amines with alcohols / CB. Dobrovolsky, A.F. Grigorov et al. (USSR). - J4 "2370915 / 23-04; declared 06/09/1976; publ. 01/30/1979, Bull. Ш 4-ЗС; A.S. 531319 USSR, B 01 J 23/86. Copper-containing catalyst for aniline alkylation / C.V. Dobrovolsky, PM Grisik et al. (USSR). - JV22153141 / 04; declared 07/04/1975; publ. 05/15/1984, Bull. JY "18-2s; Pat. 2066563, Russian Federation, IPC6 B01J23 / 84, С07С21 1/48. The catalyst for the production of Ν-methylaniline / Yakushkin M.I., Batrin Yu.D. et al., Jfs 951 10306/04, claimed 06/21/1995, publ. 09/20/1996 .; Pat. 2066679, Russian Federation, IPC 6 С07С21 1/48, B01J23 / 86. The method of obtaining N-methylaniline / Yakushkin M.I., Batrin Yu.D. et al. N2 951 10305/04, claimed 06/21/1995, publ. 09/20/1996 .; Pat. 2152382, Russian Federation, IPC ⁷ С07С21 1/48, С07С209 / 36. The method of obtaining N-alkylanilines / Starovoitov M.K., Batrin Yu.D. et al., Ν. ”98122028/04, claimed. 12/07/1998, publ. 07/10/2000 .; Pat. 2205067, Russian Federation IPC ⁷ V0ShZ / 86, S07C21 1/48. Catalyst for method of obtaining Ν-methylaniline / N.A. Mitin., S.K. Slepov. N> 2001 127908/04, claimed 10/12/2001, publ. 05/27/2003 .; Pat. 2274488, Russian Federation IPC S07C211 / 48, B01J37 / 02, B01J23 / 86. A method of producing a catalyst for the synthesis of Ν-methylaniline / C.K. Slepov, A.N. Utrobin. -Jfe 2004130567/04, claimed 10/18/2004, publ. 04/20/2006 .; Pat. 7468342, USA. The catalyst and process for the production of aromatic amines / Yoshinori Kanamori et al. - publ. December 23, 2008].

 This concludes our discussion of methods for producing N-alkylated aromatic amines using dehydrogenating catalysts and proceed to methods for producing dehydrating catalysts.

 An improved process is known for the continuous production of Ν-alkylarylanilines by reaction between arylamines and monohydric saturated alcohols and / or dialkylethers in the gas phase at a temperature of from 180 to 450 ° C. in the presence of a carrier that contains phosphoric acid. The improvement consists in the use of silicic acid having an internal surface area of from 50 to 500 m / g and containing from 0.1 to 20% by weight of phosphoric acid, as well as the continuous supply of phosphoric acid and / or alkyl phosphate to the catalyst throughout the process . The yield of Ν-monoalkylanilines and Ν, Ν-dialkylanilines is 95-98%. [Pat. 3957874, USA. Continuous production of Ν-alkylarylamines / Tony Dokner and others - publ. 05/18/1976].

A known method of producing Ν-alkylated aromatic amines by co-heating aromatic amines with lower aliphatic alcohols in the presence of phosphoric acid from 0.01 to 1.0 mol, calculated on equivalent nitrogen at a temperature of 150-280 ° C. Subsequently, the resulting liquid phase is separated with the release of Ν-alkylated aromatic amine. The duration of the process is from 30 to 130 hours, depending on the starting reagents. The following compounds were prepared by the above-described method: Dimethylaniline (99.8%), Ν, Ν-dimethyl-o-tolidine (99.4%), Ν, Ν-dimethyl-m-tolidine (99.8%), Ν, Ν -dimethyl-p-tolidine (99.8%). [Pat. 396941, USA. The process for Ν-alkylation of aromatic amines / Joachim Schneider. - publ. 07/13/1976].

A known method of producing Ν-alkylated aromatic amines, by carrying out the reaction between an aliphatic alcohol having from 1 to 6 carbon atoms and an aromatic amine having 1 hydrogen atom, bonded to nitrogen in the amino group. The reaction proceeds in the vapor phase at a temperature of 250-450 ° C in the presence of a catalyst consisting of alumina treated with hydrofluoric acid, with a yield of monoalkylamines of about 80%, with a conversion of the starting amines of about 60%. In this case, tertiary amines were formed with a yield of about 10%. Aromatic amines that can be alkylated according to the conditions described in this patent are: aniline, o-, m-, or p-toluidine, o-, m-, or p-xylidine, o-, m-, or p- anisidine and others. In this way, monoethyl-m-toluidine (48-92%) and diethyl-m-toluidine (8-22%) were obtained. The advantage of this method is the possibility of using relatively low temperatures for the reaction, and very significant drawbacks in mass production are the high cost of aldehydes and ketones and their tendency to polymerization. The patent does not indicate such important process characteristics as the load of the reaction mixture on the catalyst and the inter-regeneration run time of the catalyst. However, in this case, this is not necessary, since it is already evident from the composition of the obtained catalysis that the method is not very suitable for industrial use because of the great difficulties in separating the catalysis of this composition into components. [Pat. 4029707, USA. Production of Ν-alkylated aromatic amines / Charles W. Hargis. - publ. 06/14/1977].

 A known method of producing Ν-alkylated aromatic amines by carrying out the reaction between aliphatic or cycloaliphatic alcohols and aromatic amines at elevated temperature and elevated pressure in the presence of catalysts. The reaction is carried out in the presence of phosphorus oxyhalides. The temperature at which the alkylation process takes place is 200-400 ° C, the pressure is 3-20 MPa. The yield of the target products for--alkylanilines is 43-46%, for Ν, Ν-dialkylanilines 3-8%. The remaining amount is the unreacted aromatic amine. [Pat. 4268458, USA. Process for the production of Ν-alkylated aromatic amines / Werner Schulte-Hermann, Heinz Hemmerich. - publ. 05/19/1981].

A known method for producing para-substituted aromatic amines by conducting a para-substitution reaction of an aromatic carbamic acid ester with an aromatic amine in the presence of aliphatic or cycloaliphatic alcohols. The reaction is carried out at a temperature of 100-260 ° C, at reduced or atmospheric pressure. As a result of the para-substitution reaction, according to the above method, the following compounds were obtained: 4-tert-pentylaniline (83% of theory) and 4-tert-butylaniline (80% of theory). [Pat. 4359584, USA. Production of p-substituted aromatic amines / Franz Merger, Gerhard Nestler. - publ. November 16, 1982].

A known method of producing Ν-alkyl and Ν, Ν-dialkylaniline by carrying out the alkylation of aniline with alcohols, preferably with methanol or ethanol, in the presence of a ZSM-5 catalyst. The use of the modified ZSM-5 catalyst enhances the selectivity for N-alkylation, while at the same time, the formation of undesirable by-products such as toluidines is suppressed. The molar ratio of silicon oxide to alumina in the catalyst is from 20: 1 to 700: 1, more preferably a ratio of from 30: 1 to 200: 1. The aluminosilicate can be modified using alkaline, alkaline earth or transition metal ions, preferably cesium, potassium, magnesium and iron. The reagents are contacted in the presence of a catalyst at a temperature of from 300 to 500 ° C, at a pressure of from 1 to 3 atm. and when the molar ratio of alcohol to aniline is from 1 to 6. The feed rate is from 0.2 to 4 g of raw material / g of catalyst / hour. As a result, Ν-methylaniline (51-89%) and Ν, Ν-dimethylaniline (9-40%) were obtained, depending on the type used catalyst. [Pat. 4801752, USA. Production of N-alkyl and Ν, Ν-dialkylanilines / Po Io Chen et al. - publ. 01/31/1989].

 We studied the issues of alkylation of aniline in the vapor phase, methanol, on ZSM-5 zeolites. As a result, it was found that the selectivity for C- and Ν-alkylation directly depends on the acid-base properties of the catalyst, and with an increase in the basicity of the zeolite, its activity and selectivity in the direction of Ν-alkylation increase. The inter-regeneration run of the used catalysts is not indicated. [Chen P.Y., Chu H.Y., Chuang T.K., Chem.Abs, v. 107, 1987]. This conclusion was confirmed by the Ν-alkylation of o-toluidine with methanol on acidic Η-β-zeolite. So, during the reaction on this catalyst at a temperature of 400 ° C, mainly 2,4-xylidine (69%) and 2,6-xylidine (up to 4%) were formed, i.e. mainly C-alkylation occurred. The inter-regeneration run of the used catalysts is not indicated. [Anand R., Maheswari R., Journal of molecular catalysis A: Chemical, 192, p. 253, 2003]. A comparison of the results obtained on catalysts with phosphoric acid and zeolites shows that in the case of aniline methylation they are very close, and in the case of aniline ethylation, the process is much better on zeolites.

The known method of алки-alkylation of anilines by conducting in the vapor phase the reaction of anilines with lower alcohols or dialkyl ethers at elevated temperatures and in the presence of pentasilic type zeolite catalysts containing protons and having an S1O2 / AI2O3 ratio of at least 60. The temperature at which the reaction proceeds is 220-370 ° C. The following were obtained: Ν-monomethylaniline (1-62%), Ν, Ν-dimethyaniline (5-93%), Ν-ethylaniline (20-52%), N-diethylaniline (4-6%), Ν-ethyl- m-toluidine (50-52%) and Ν, Ν-diethyl-m-toluidine (5-6%) depending on the type of catalyst used and the alcohol: aniline ratio. The inter regeneration run of the used catalysts is not indicated. [Pat. 5068434, USA. The process for the preparation of Ν-alkylated anilines / Gunter Klug et al. - publ. 26.1 1.1991].

 A gas-phase process is known, which includes the step of reacting a primary aromatic amine (aniline or substituted aniline) with an alcohol having from 1 to 5 carbon atoms or with ether under conditions of проведения-alkylation using gallosilicate. The reaction proceeds at a temperature of from 200 to 500 ° C and atmospheric pressure. As a result of the process, Ν-methylaniline is obtained. The selectivity of the alkylation process is from 40 to 90%, depending on the catalyst used and the process conditions. [Pat. 5159115, USA. Catalytic gas-phase process of Ν-alkylation of aromatic primary amines / Peter G. Pappas et al. - publ. 10/27/1992].

 The алки-alkylation of aromatic amines by the vapor-phase method on dehydrating catalysts has the following disadvantages:

- low conversion and selectivity of the process, which leads to a very high content in the catalyst of the starting amine, dialkylamine and C-alkylamines, which greatly complicates the isolation of the target monoalkylamine by distillation;

 - high process temperature, which causes problems with coolants and reduces the inter-regeneration range of the catalyst due to its resinification;

 - low mileage of the catalyst, which leads to such negative consequences as, a decrease in production time, a decrease in the degree of automation of the process, an increase in capital costs for equipment and labor.

 Based on this, Ν-alkylation on dehydrating catalysts is not advisable for the production of Ν-methyl-para-phenethidine.

When analyzing literature and patent sources concerning methods for the production of алки-alkyl-substituted aromatic amines, we were not able to find materials describing the method for producing Ν-methyl-para-phenethidine from para-phenetidine or paratrophenetole, as well as the conditions and parameters for its receipt. A number of materials indicate the possibility of methylation in a certain way, including paraphenetidine, but no specific examples are given. In addition, in some cases, it is not economically feasible to obtain метил-methyl-para-phenethidine by the methods described in them, or these methods are not relevant to our invention. It was also possible to find the USSR copyright certificate, which considers the possibility of alkylation of para-phenetidine with C5-C9 aliphatic alcohols, in the liquid phase, on Raney nickel, when boiling under reflux, but not methanol, in connection with which, these studies are not related to the essence of our invention.

 Many works on the alkylation of aromatic amines indicate that this process is quite complicated. The selection of raw materials, alkylating agents, selective, productive and sustainable catalyst, as well as process conditions, is an individual task for each compound.

The aim of the invention is to provide the possibility of obtaining Ν-methyl-para-phenethidine with a purity of not less than 98% and a high yield, allowing you to organize highly profitable, multi-tonnage production.

Closest to the proposed method for the production of Ν-methyl-para-phenethidine is the method [RF patent 2135460] of the joint production of aniline and Ν-methylaniline from nitrobenzene and methanol in the vapor phase on the heterogeneous copper-chromium catalyst NTK-4. The method according to this patent is chosen by us as a prototype according to the totality of common features. In accordance with this method, depending on the methanol-nitrobenzene ratio, mainly aniline or Ν-methylaniline is obtained in high yield. The advantages of this method are its versatility and simplicity of equipment, the absence of high pressure. To obtain Ν-methyl-para-phenethidine, this method was not used.

The technical result is achieved by Ν-alkylation of para-nitrophenetole or para-phenetidine with methanol in the vapor phase, with atmospheric pressure and a temperature of 180-260 ° C, on dehydrogenating Raney nickel and copper-chromium modified oxides of barium, calcium, zinc, etc., including industrial series NTK and BASF. Specifically, catalysts were used having the following composition:

CuO- 55%; ZnO - 10.5%; Cr ₂ 0 ₃ - 13.5%; A1 ₂ 0 _{3 the} rest;

CuO- 25%; ZnO - 25%; CaO - 5%; A1 ₂ 0 _{3 the} rest;

CuO- 25-45%; BaO- 2-10%; Youth Theater - 15-35%; Cg ₂ O _{e the} rest;

CuO- 35-45%; ZnO- 25-35%; NiO- 3-8%; A1 ₂ 0 _{3 the} rest;

CuO- 12-19%; MnO - 2-3%; Cr ₂ O _e - 1.0-1.4%; Fe ₂ 0 ₃ - 1, 0-1.4%; Co ₃ 0 ₄ - 0.5-0.8%; A1 ₂ 0 _{3 the} rest; Raney nickel catalyst; BASF Cu-E403TR catalyst produced by composition: copper chromite 67-71%), copper 11-15%, copper oxide 8-21%, graphite 0-4%, chromium oxide (3+) 0-3%; BASF production catalyst Cu-0203T 1/8 composition: copper oxide 75-100%, chromium oxide (3+) 0.1-1%; BASF production catalyst Cu-E406TR composition: Cu-36%, Cr-31%, Ba-6%.

To increase the selectivity of the process for отношении-methyl-para-phenethidine, it is proposed to introduce triethylamine into the reaction mixture, which inhibits the formation of Ν, Ν-dimethyl- para-phenethidine, in a molar ratio to the starting nitro compound (0.05-0, 1): 1. With a ratio of less than 0.05: 1, the effect is practically not observed, with a ratio of more than 0.1: 1, difficulties arise with isolation of triethylamine and its return to contacting.

The conditions for the production of Ν-methyl-para-phenethidine are illustrated by the following examples:

Example 1. In a quartz tube with an inner diameter of 45 mm, 100 ml of copper-chromium catalyst and 100 ml of inert material (broken quartz, ceramic Rashig rings) used to improve the evaporation of the reagents were loaded. Nitrogen was passed through the tube at a rate of 200 ml / min and heated with an electric heater to a temperature of 200 ° C. At this temperature, catalyst recovery was started by feeding a 5% aqueous solution of methanol into the tube so that the temperature in the catalyst layer did not rise above 300 ° C. After completion of the recovery (the cessation of heat generation and a drop in temperature in the catalyst layer to 200 ° C) for another 1 hour, pure methanol vapor was passed through a quartz tube. Methanol was replaced with a mixture consisting of 1 molar part of para-nitrophenetole and 5 molar parts of methanol, which was supplied at a rate of 0.125 - 0.3 L / h and the synthesis of метил-methyl-para-phenetidine was carried out. Contact gases were cooled in a glass ball cooler and collected in a collector. The condensate was divided into aqueous and organic layers in a phase separator. The organic layer was analyzed by GLC. The contacting process was conducted continuously until the appearance in the organic layer 5-% para-nitrophenetol catalysis. Then the flow of the reaction mixture was stopped and the installation was switched to the catalyst regeneration mode. To do this, water vapor was supplied to the catalyst, then water vapor was diluted with air, gradually increasing its concentration, but so that the temperature in the catalyst layer did not exceed 350 ° C. After the regeneration (cessation of heat generation in the catalyst bed), the installation was transferred to the recovery mode and then to the contact mode (described above). The average yield for the period of contact (200-250 hours) was 80-85%.

 The collected organic layer was separated in a batch distillation unit, intermediate products and methanol were returned for contacting. Commodity Ν-methyl-para-phenethidine was obtained with a concentration of 98%.

 Example 2. As in example 1, but instead of para-nitrophenetol, para-phenetidine was used. The load of the mixture on the catalyst is 0.3-0.4 l / h. The catalyst in the oil layer contains 0-8% para-phenetidine, 90-95% N-methyl-phenethidine and 1-5% Ν, Ν-dimethyl-para-anisidine. Received Ν-methyl-para-phenethidine with a yield of 85-90%).

 Example 3. As in example 1, the process was conducted in a stream of nitrogen.

 Example 4. As in example 1, the process was conducted in a stream of hydrogen.

 Example 5. As in example 2, the process was conducted in a stream of nitrogen.

Example 6. As in example 2, the process was conducted in a stream of hydrogen, with a ratio of 1 molar part of para-phenetidine and 2 molar parts of methanol. Example 7. As in example 1, 3, 4, but in the presence of triethylamine in a molar ratio to para-nitrophenetole of 0.1: 1. Received Ν-methyl-para-phenethidine with a yield of up to 92%.

 Example 8. As in example 2, 5, 6, but in the presence of triethylamine in a molar ratio to para-phenethidine of 0.1: 1. Received Ν-methyl-para-phenethidine with a yield of up to 96%.

Examples N21,2,3, 4,5, 6,7,8 were carried out on catalysts of the following compositions:

CuO- 55%; ZnO - 10.5%; Cr ₂ O _e - 13.5%; A1 ₂ 0 _{3 the} rest;

CuO- 25%; ZnO - 25%; CaO - 5%; A1 ₂ O _{e the} rest;

CuO- 25-45%; BaO- 2-10%; TU ₃ - 15-35%; Cr ₂ 0 _{3 the} rest;

CuO- 35-45%; ZnO- 25-35%; NiO- 3-8%; A1 ₂ 0 _{3 the} rest;

CuO- 12-19%; MnO - 2-3%; Cr ₂ 0 ₃ - 1.0-1.4%; Fe ₂ 0 ₃ - 1.0-1.4%; Co ₃ 0 ₄ - 0.5-0.8%; A1 ₂ 0 _{3 the} rest;

 Raney nickel catalyst;

 BASF Cu-E403TR catalyst produced by composition: copper chromite 67-71%, copper 1 1-15%, copper oxide 8-21%, graphite 0-4%, chromium oxide (3+) 0-3%;

 BASF production catalyst Cu-0203T 1/8 composition: copper oxide 75-100%, chromium oxide (3+) 0.1-1%;

 BASF production catalyst Cu-E406 TR composition: Cu-36%, Cr-31%, Ba-6%.

 Similar results are obtained. Resource catalysts up to 2000 hours.

Claims

CLAIM 1. The method of producing Ν-methyl-para-phenethidine, which consists in the fact that the алки-alkylation of para-nitrophenetole and / or para-phenetidine is carried out with methanol in the vapor phase on a dehydrogenation catalyst at a temperature of 180-260 ° C and atmospheric pressure, followed by distillation of products.  2. The method according to claim 1, characterized in that Ν-methyl-para-phenethidine is obtained, respectively, from para-nitrophenetol.  3. The method according to claim 1, characterized in that Ν-methyl-para-phenethidine is obtained, respectively, from para-phenetidine.  4. The method according to claim 1, characterized in that the Ν-alkylation is carried out in a stream of nitrogen.  5. The method according to claim 1, characterized in that the Ν-alkylation is carried out in a stream of hydrogen.  6. The method according to claim 1, characterized in that the catalyst has the composition: CuO - 55%; ZnO - 10.5%; Cr ₂ O _e - 13.5%; A1 ₂ 0 _{3 the} rest. 7. The method according to claim 6, characterized in that it has the composition: CuO - 25%; ZnO - 25%; CaO - 5%; A1 ₂ 0 _{3 the} rest.  8. The method according to claim 6, characterized in that the catalyst has the composition: CuO - 25-45%; BaO - 2-10%; TU ₃ - 15-35%; Cg ₂ O _{e the} rest.  9. The method according to claim 6, characterized in that the catalyst has the composition: CuO - 35-45%; ZnO - 25-35%; NiO - 3-8%; A1 ₂ 0 _{3 the} rest.  10. The method according to claim 6, characterized in that the catalyst has the composition: CuO - 12-19% MnO - 2-3%; Cr ₂ 0 ₃ - 1, 0-1, 4%; Fe ₂ 0 ₃ - 1, 0-1.4%; Co ₃ 0 ₄ - 0.5-0.8%; A1 ₂ 0 _{3 the} rest. 1 1. The method according to claim 6, characterized in that a Raney nickel catalyst is used.  12. The method according to claim 6, characterized in that the BASF Cu-E403TR catalyst is used, which has the composition: copper chromite 67-71%, copper 1 1-15%, copper oxide 8-21%, graphite 0-4%, chromium oxide (3+) 0-3%.  13. The method according to claim 6, characterized in that a BASF Cu-0203T 1/8 catalyst is used, which has the composition: copper oxide 75-100%, chromium oxide (3+) 0.1-1%.  14. The method according to claim 6, characterized in that the catalyst used is the production of BASF Cu-E406 TR, which has the composition: Cu - 36%, Cr - 31%, Ba - 6%.  15. The method according to claim 1, characterized in that the Ν-alkylation process is carried out in the presence of triethylamine in a molar ratio to para-nitrophenetole and / or para-phenethidine 0-0.1: 1.