RU2471771C1 - Method for selective production of n-methyl-para-phenetidine - Google Patents

Abstract

FIELD: chemistry.

SUBSTANCE: invention relates to chemical engineering processes and specifically to methods for catalytic alkylation of aromatic amines and nitro compounds. N-methyl-para-phenetidine is obtained from para-phenetidine and/or para-nitrophenetole by N-alkylation with methanol in vapour phase on a dehydration catalyst at temperature of 180-260°C and atmospheric pressure, followed by separation of products by rectification.

EFFECT: possibility of selective production of N-methyl-para-phenetidine with purity of not less than 98% and high output, which enable highly profitable, large-tonnage production.

15 cl, 8 ex

Description

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 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 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.

N-methyl-para-phenethidine is currently used as an antiknock additive or additive to motor fuel [US Pat. 2309943, Russian Federation, IPC С07С 217/82, С07С 235/24, C10L 1/223, C10L 1/224. The use of derivatives of para-ethoxyanilines that increase the resistance of hydrocarbon fuels to detonation, and fuel composition (options) / Ivanov Yu.A., Frolov A.Yu. et al. - No. 2006108236/04, declared 03/16/2006, publ. November 10, 2007, Bull. No. 31].

Given the unique properties of N-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 N-methyl-para-phenethidine is a very urgent task.

A known method of producing N-methyl-para-phenethidine [US Pat. 2309943, Russian Federation, IPC С07С 217/82, С07С 235/24, C10L 1/223, C10L 1/224. The use of derivatives of para-ethoxyanilines that increase the resistance of hydrocarbon fuels to detonation, and fuel composition (options) / Ivanov Yu.A., Frolov A.Yu. et al. - No. 2006108236/04, declared 03/16/2006, publ. November 10, 2007, Bull. No. 31], which provides reliable evidence that N-methyl-para-phenethidine is actually obtained, its physicochemical and spectral studies confirming its structure are presented. In this work, N-methyl-para-phenethidine was obtained in two ways: from N-methyl-N-acetyl-para-phenetidine 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 p.], 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 N-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. A method of obtaining N-alkyl-P-phenetidines / L.A. Skripko (USSR). - No. 805091 / 23-4; declared 11/29/1962; publ. 11/10/1964, Bull. No. 21 - 2 S.], which proposed a method of 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 para-phenetidine in a specific aliphatic alcohol. In this way, N-amyl-para-phenethidine, N-decyl-para-phenethidine, N-cyclohexyl-para-phenetidine were obtained. The yield of target products amounted to 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 N-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 a solution of para-phenetidine in methanol boils at a temperature below 100 ° C, at which methanol is not dehydrogenated, and therefore methylation is not carried out.

The lack of information on the N-methylation of para-phenethidine led us to pay attention to the methods for producing N-alkylated anilines, which are close in structure to our facility, for which there is enough information. At the same time, 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 N-alkylation and to N, N-dialkylation. This fact imposes certain restrictions on the possibility of transferring the data obtained during the N-alkylation of aniline to the synthesis of N-methyl-para-phenethidine. The second limitation is the ethereal nature of para-phenetidine, which does not allow the use of N-alkylation methods, leading to hydrolysis of the ester.

With these limitations in mind, the following materials were reviewed on processes for preparing N-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, A01N 5/00. A method of obtaining N-alkylanilines / G.V. Esipov, A.V. Yazlovitsky, N.A. Onishchenko, I.E. Kishkovskaya (USSR). - No. 2484138 / 23-04; declared 05/10/1977; publ. 06/05/1979, Bull. No. 21 - 3 p.].

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 N-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 HTK series, to produce aniline and N-methylaniline. The yield of N-methylaniline and aniline in terms of nitrobenzene is 95% [US Pat. 2135460, Russian Federation, IPC ⁶ С07С 209/36, С07С 209/16, С07С 211/46, С07С 211/48. Joint production of aniline and N-methylaniline / Batrin Yu.D., Nikolaev Yu.T. et al. - No. 97120738/04, declared December 16, 1997, publ. August 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 N-methyl-para-phenetidine. These disadvantages are common to all production methods in which the alkylated feed is aromatic nitro compounds. A common drawback is also the increased content of tertiary amine impurities, especially in the initial period of contacting.

Known is an improved method for producing N-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 brand "Virgon", or "C-40", or "NTK-10-7F", modified with nickel, or palladium, or platinum, taken in an amount of 0.3-10 wt.%. 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 h ^-1 , maintaining the ratio of methanol / aromatic nitro compound in the initial mixture from 1: 1 to 5 :one. The total yield of aromatic amines up to 99.5%, product productivity up to 0.4-1.3 g / g h. The method allows, depending on the ratio of reagents used, to change the ratio of the obtained N-methyl-substituted and unsubstituted aromatic amines [US Pat. 2207335, Russian Federation, IPC ⁷ C07C 211/48, С07С 211/46, С07С 209/36. A method of producing aromatic amines by reduction of the corresponding nitro compounds / Vinokurov V.A., Stytsenko V.D. et al. - No. 2001111547/04, declared 04/28/2001, publ. June 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 can be justified only by its increased service life, which is not indicated in the patent.

Known is an improved method for producing N-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 cheapen the technology, reduce energy consumption [Pat. 2240308, Russian Federation, IPC ⁷ С07С 211/48, С07С 209/26. The method of obtaining N-methylaniline / Gorbunov B.N., Slepov S.K. et al. - No. 2003106495/04, declared 03/07/2003, publ. November 20, 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 N-methylaniline from nitrobenzene, methanol and hydrogen in the gas phase on a copper-containing catalyst, including 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, of the following composition: copper oxide 37-40 wt.%, chromium oxide 18-20 wt. .%, zinc oxide 20 wt. .%, alumina - the rest, or in both contact devices as a copper-containing catalyst, a composition catalyst is used: copper oxide 21.4-26.4 wt.%, chromium oxide 3.4-5.8 wt.%, alumina 3 , 3-22.3 wt.%, Double chromite of copper and zinc of the empirical formula ZnxCuyCr ₂ O ₄ , where x = 0.8-10, y = 0.4-0.9, 54.5-71.9 wt. % [Pat. 2263107, Russian Federation IPC ⁷ 211/48 S07S, S07S 209/26. A two-stage method for producing N-methylaniline / Gorbunov BN, Utrobin AN et al. - No. 2003131054/04, declared 10/22/2003, publ. October 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 N-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 a 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 sent to reductive alkylation [Pat. 2275353, Russian Federation IPC С07С 209/36, С07С 211/48. The method of obtaining N-methylaniline / Gorbunov B.N., Slepov S.K. et al. - No. 2004107764/04, declared 03/15/2004, publ. April 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.

Known is an improved method for producing N-methylaniline by reductive N-alkylation of aniline. 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 carry out the recovery of the catalyst [Pat. 2270187, Russian Federation IPC С07С 209/36, С07С 211/48. A method of obtaining N-methylaniline / V.A. Golovachev, V.N. Dogadaev. - No. 2004111480/04, 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. Alkylation of aniline is carried out with formalin in the ratio of aniline: formalin = 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 number of swings 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 reduce the proportion of by-products [US Pat. 2270831, Russian Federation IPC С07С 211/48, С07С 209/26, B01J 23/44, B01J 35/04. The method of liquid-phase catalytic alkylation of aniline / A.A. Revin, A.I. Kozlov, etc. - No. 2004133550/04, decl. 11/18/2004, publ. 02/27/2006]. Disadvantages - it is impossible to ensure the selectivity of the process in relation to monomethylaniline. It is for this reason, trying to somehow increase the selectivity, the process is carried out with a lack of formalin at aniline: formalin ratio of 1.6: 1.1. Very expensive catalyst. This 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 highly porous alumina-based cellular support with a porosity of at least 70-95% and a palladium active component 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 [US Pat. 2285691, Russian Federation IPC С07С 211/48, С07С 209/26, B01J 21/04, B01J 23/44, B01J 35/04. The method of liquid-phase catalytic alkylation of aromatic amines / A.I. Kozlov, V.N. Grunsky, A.V. Bespalov. - No. 2005112854/04, declared 04/28/2005, publ. October 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 N-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 С07С 211/48, С07С 211/46, С07С 209/26, С07С 209/36. A method of producing aniline and / or N-methylaniline and a catalyst for it / B.N. Gorbunov, S.K. Slepov. - No. 2003121732/04, declared 07/14/2003, publ. February 27, 2005]. The disadvantage is the large additional amount of contaminated water sent for disposal, which significantly affects the economic performance of the process.

A known method for producing N-methylaniline by catalytic hydrogenation of nitrobenzene with hydrogen in the presence of methanol on a copper-aluminum 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% at 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% [US Pat. 2223258, Russian Federation IPC ⁷ С07С 211/48, С07С 209/36. The method of obtaining N-methylaniline / Yu.D. Batrin, M.K. Starovoitov and others. - No. 2003100842/04, decl. 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.

A known two-stage method for producing N-methylaniline by vapor-phase catalytic N-alkylation of aniline with methanol: the aniline and methanol in a molar ratio of 1: 2 are fed to the first stage and the process is carried out at a temperature of 230-260 ° C and a contact load of 0.7-0.9 h ^{- 1} to the degree of conversion of aniline to N-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 N-methylaniline is more than 98%, using catalysts based on both stages copper oxides promoted by metal oxides from a group including manganese, iron, chromium, nickel, cobalt. Effect: obtaining 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 C07C 211/48, C07C 209/18. A two-stage method for producing N-methylaniline / N.A. Mitin, S.K. Slepov et al. - No. 2002121792/04, decl. 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, such a problem in one way or another (selection of a catalyst, selection of modes, etc.) is solved in any of the considered methods for producing N-alkylated arylamines and, apparently, a zone approach is also possible.

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

where R ₁ is one of the radicals selected from N, CH ₃ , C ₂ H ₅ ,

R ₂ is one of the radicals selected from N, CH ₃ , C ₂ H ₅ ,

R ₃ is H or a radical CH ₃ , C ₂ H ₅ on an NTK series catalyst at a temperature of 230-270 ° C, characterized in that, in order to save energy, the required amount of nitrobenzene or its derivative corresponding to the obtained alkylaniline is added to the initial reaction mixture, general formula

where R ₃ is H or a radical CH ₃ , C ₂ H ₅ , through which the required reactor temperature is maintained [Application 2002130524, Russian Federation, IPC ⁷ C07C 211/48, C07C 209/60. A method of obtaining N-alkylanilines / T.V. Rudakova, A.F. Kachegin and others. - No. 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 N-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 С07С 211/48, С07С 209/18. The method of obtaining N-methylaniline / N.G. Belyakov, N.I. Vavilov, etc. - No. 2003100063/04, decl. 01/09/2003, publ. July 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 N-methylaniline from nitrobenzene methanol and hydrogen in the gas phase at a coolant temperature of 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 the release of aniline in salable form at atmospheric pressure on a copper oxide catalyst comprising 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, IPC ⁷ С07С 211/48. A method of obtaining N-methylaniline / Yu.T. Nikolayev, N.G. Belyakov. - No. 2004104170/04, declared 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 N-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 N-methylaniline from aniline and methanol using a stoichiometric excess of alcohol, which greatly increases the conversion of aniline to N-methylaniline and completely inhibits the formation of N, N-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 [US Pat. 2580284, USA. The production of secondary aromatic amines / Thomas Jay Deal and others - publ. December 25, 1951]. The catalyst contains a large amount of acidic aluminum oxide; therefore, when using this method to obtain N-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%. As an alkylation catalyst, Raney nickel is used [US Pat. 2813124, USA. Preparation of secondary aromatic amines / Rip G. Rice and others - publ. November 12, 1957]. The disadvantage is the low yield of the secondary amine.

A known method for the production of N-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. In the presence of a catalyst consisting of copper and chromium and corresponding to the formula: Cr · Me ¹ · Me ² · O, where Me ¹ is Cu, Zn, Fe or Ni, Me ² is Ba, Ca, Mg or Mn, Cr. The metal content in the catalyst: Cr from 20 to 80 wt.%, Me ¹ from 20 to 80 wt.%, Me ² from 0 to 5 wt.%. The yield of N-methylaniline is 95% [US Pat. 3819709, USA. Synthesis of N-methylaniline / Koichi Murai et al. - 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, B01J 23/76, B01J 21/06, C07B 27/00. A catalyst for the alkylation of aromatic amines with alcohols / S.V. Dobrovolsky, A.F. Grigorov et al. (USSR). - No. 2370915 / 23-04; declared 06/09/1976; publ. 01/30/1979, Bull. No. 4 - 3 s .; A.S. 531319 USSR, B01J 23/86. Copper-containing catalyst for aniline alkylation / S.V. Dobrovolsky, PMGrizik et al. (USSR). - No. 2153141/04; declared 07/04/1975; publ. 05/15/1984, Bull. No. 18 - 2 s .; Pat. 2066563, Russian Federation, IPC ⁶ B01J 23/84, С07С 211/48. The catalyst for the production of N-methylaniline / Yakushkin M.I., Batrin Yu.D. et al. - No. 95110306/04, declared 06/21/1995, publ. 09/20/1996; Pat. 2066679, Russian Federation, IPC ⁶ С07С 211/48, B01J 23/86. The method of obtaining N-methylaniline / Yakushkin M.I., Batrin Yu.D. et al. - No. 95110305/04, declared 06/21/1995, publ. 09/20/1996; Pat. 2152382, Russian Federation, IPC ⁷ С07С 211/48, С07С 209/36. A method of producing N-alkylanilines / Starovoitov M.K., Batrin Yu.D. et al. - No. 98122028/04, declared. 12/07/1998, publ. 07/10/2000; Pat. 2205067, Russian Federation IPC ⁷ B01J 23/86, С07С 211/48. A catalyst for the production of N-methylaniline / N.A. Mitin, S.K. Slepov. - No. 2001127908/04, declared 10/12/2001, publ. 05/27/2003; Pat. 2274488, Russian Federation IPC С07С 211/48, B01J 37/02, B01J 23/86. A method of producing a catalyst for the synthesis of N-methylaniline / S.K. Slepov, A.N. Utrobin. - No. 2004130567/04, declared 10/18/2004, publ. 04/20/2006; Pat. 7468342, USA. The catalyst and the process for the production of aromatic amines / Yoshinori Kanamori and others - publ. December 23, 2008].

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

An improved process is known for the continuous production of N-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 ² / g and containing from 0.1 to 20 wt.% Phosphoric acid, as well as in the continuous supply of phosphoric acid and / or alkyl phosphate to the catalyst throughout process. The yield of N-monoalkylanilines and N, N-dialkylanilines is 95-98% [US Pat. 3957874, USA. Continuous production of N-alkylarylamines / Tony Dokner and others - publ. 05/18/1976].

A known method of producing N-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 N-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%), N, N-dimethyl-o-tolidine (99.4%), N, N-dimethyl-m-tolidine (99.8%), N, N -dimethyl-p-tolidine (99.8%) [US Pat. 396941, USA. Process for N-alkylation of aromatic amines / Joachim Schneider. - publ. 07/13/1976].

A known method of producing N-alkylated aromatic amines by carrying out a reaction between an aliphatic alcohol having from 1 to 6 carbon atoms and an aromatic amine having 1 hydrogen atom bound 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 carrying out the reaction, and very significant disadvantages 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 the composition of the obtained catalysis is already evident that the method is not suitable for industrial use because of the great difficulties in separating the catalysis of this composition into components [Pat. 4029707, USA. Production of N-alkylated aromatic amines / Charles W. Hargis. - publ. 06/14/1977].

A known method of producing N-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 is 43-46% for N-alkylanilines, and 3-8% for N, N-dialkylanilines. The remaining amount falls on the unreacted aromatic amine [US Pat. 4268458, USA. Process for the production of N-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 theoretical) and 4-tert-butylaniline (80% of theoretical) [US Pat. 4359584, USA. Production of p-substituted aromatic amines / Franz Merger, Gerhard Nestler. - publ. November 16, 1982].

A known method of producing N-alkyl and N, N-dialkylaniline by carrying out the alkylation reaction of aniline with alcohols, preferably with methanol or ethanol, in the presence of a ZSM-5 catalyst. The use of a 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 300 to 500 ° C, at a pressure of 1 to 3 atm and with a molar ratio of alcohol to aniline of 1 to 6. The feed rate is from 0.2 to 4 g of feed / g of catalyst / hour . As a result, N-methylaniline (51-89%) and N, N-dimethylaniline (9-40%) were obtained, depending on the type of catalyst used [Pat. 4801752, USA. Production of N-alkyl and N, N-dialkylanilines / By Yo Chen et al. - publ. 01/31/1989].

We studied the issues of alkylation of aniline in the vapor phase with methanol on ZSM-5 zeolites. As a result, it was found that the selectivity for C- and N-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 N-alkylation increase. The inter-regeneration run of the used catalysts is not indicated [Chen P.Y., Chu H.Y., Chuang T.K., Chem.Abst., V.107, 1987]. This conclusion was confirmed by N-alkylation of o-toluidine with methanol on acid N-β-zeolite. So, during the reaction on this catalyst at a temperature of 400 ° C, 2,4-xylidine (69%) and 2,6-xylidine (up to 4%) were mainly formed, i.e. mainly C-alkylation occurred. The inter-regeneration run of the catalysts used 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.

A known method of N-alkylation of anilines by conducting in the vapor phase reaction of anilines with lower alcohols or dialkyl ethers at elevated temperature and in the presence of pentasilic type zeolite catalysts containing protons and having a SiO ₂ / Al ₂ O ₃ ratio of at least 60. The temperature at which the reaction proceeds, makes 220-370 ° C. Received: N-monomethylaniline (1-62%), N, N-dimethyaniline (5-93%), N-ethylaniline (20-52%), N, N-diethylaniline (4-6%), N-ethyl -m-toluidine (50-52%) and N, N-diethyl-m-toluidine (5-6%) depending on the type of catalyst used and the ratio of alcohol: aniline. The inter-regeneration run of the used catalysts is not specified [US Pat. 5068434, USA. The process for the preparation of N-alkylated anilines / Gunter Klug and others - publ. November 26, 1991].

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

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

In the analysis of literature and patent sources relating to methods for producing N-alkyl substituted aromatic amines, we were not able to find materials describing a method for producing N-methyl-para-phenethidine from para-phenetidine or para-nitrophenetole, as well as the conditions and parameters for its receipt. A number of materials indicate the possibility of methylation in a certain way, including para-phenethidine, but no specific examples are given. In addition, in some cases, it is not economically feasible to obtain N-methyl-para-phenethidine by the methods described in them, or these methods are not relevant to the essence of our invention. It was also possible to find the USSR author’s certificate, which considers the possibility of alkylation of para-phenetidine with C5-C9 aliphatic alcohols, in the liquid phase, on Raney nickel, when boiled under reflux, but not with methanol, and therefore these studies are not relevant 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 N-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 producing N-methyl-para-phenethidine is the method [RF patent 2135460] for the joint production of aniline and N-methylaniline from nitrobenzene and methanol in the vapor phase on a 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 N-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 N-methyl-para-phenethidine, this method was not used.

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

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

CuO - 25%; ZnO - 25%; CaO - 5%; Al ₂ O _{3 the} rest;

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

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

CuO - 12-19%; MnO - 2-3%; Cr ₂ O ₃ - 1.0-1.4%; Fe ₂ O ₃ - 1.0-1.4%; Co ₃ O ₄ - 0.5-0.8%; Al ₂ O _{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 Cu-E406TR production catalyst composition: Cu - 36%, Cr - 31%, Ba - 6%.

To increase the selectivity of the process with respect to N-methyl-para-phenethidine, it is proposed to introduce triethylamine, which inhibits the formation of an impurity of N, N-dimethyl-para-phenethidine, in a molar ratio to the initial nitro compound (0.05-0.1): 1 . With a ratio less than 0.05: 1, the effect is practically not observed, with a ratio greater than 0.1: 1, difficulties arise in isolating triethylamine and returning it to contact.

The conditions for obtaining N-methyl-para-phenetidine 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 (crushed quartz, ceramic Raschig rings) used to improve the evaporation of 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 methanol solution to the tube at a rate such that the temperature in the catalyst bed 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 N-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 carried out continuously until the appearance of 5% para-nitrophenetol catalyst in the organic layer. After which the flow of the reaction mixture was stopped and the installation was switched to the catalyst regeneration mode. For 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 contacting 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 N-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 para-phenetidine 0-8%, N-methyl-para-phenetidine 90-95% and N, N-dimethyl-para-anisidine 1-5%. Received N-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-nitrophenol 0.1: 1. Received N-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 N-methyl-para-phenethidine with a yield of up to 96%.

Examples No. 1, 2, 3, 4, 5, 6, 7, 8 were carried out on catalysts of the following compositions:

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

CuO - 25%; ZnO - 25%; CaO - 5%; Al ₂ O _{3 the} rest;

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

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

CuO - 12-19%; MnO - 2-3%; Cr ₂ O ₃ - 1.0-1.4%; Fe ₂ O ₃ - 1.0-1.4%; Co ₃ O ₄ - 0.5-0.8%; Al ₂ O _{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 Cu-E406 TR production catalyst composition: Cu - 36%, Cr - 31%, Ba - 6%. Similar results are obtained. Resource catalysts up to 2000 hours.

Claims (15)

1. The method of obtaining N-methyl-para-phenethidine, which consists in the fact that the N-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 isolation rectification products. 2. The method according to claim 1, characterized in that N-methyl-para-phenethidine is obtained respectively from para-nitrophenetole. 3. The method according to claim 1, characterized in that N-methyl-para-phenethidine is obtained respectively from para-phenetidine. 4. The method according to claim 1, characterized in that the N-alkylation is carried out in a stream of nitrogen. 5. The method according to claim 1, characterized in that the N-alkylation is carried out in a stream of hydrogen. 6. The method according to claim 1, characterized in that the catalyst has a composition: CuO 55%; ZnO 10.5%; Cr ₂ O ₃ 13.5%; Al ₂ O _{3 the} rest. 7. The method according to claim 6, characterized in that it has the composition: CuO 25%; ZnO 25%; CaO 5%; Al ₂ O _{3 the} rest. 8. The method according to claim 6, characterized in that the catalyst has a composition of: CuO 25-45%; BaO 2-10%; TiO ₃ 15-35%; Cr ₂ O _{3 the} rest. 9. The method according to claim 6, characterized in that the catalyst has a composition of: CuO 35-45%; ZnO 25-35%; NiO 3-8%; Al ₂ O _{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 O ₃ 1.0-1.4%; Fe ₂ O ₃ 1.0-1.4%; Co ₃ O ₄ 0.5-0.8%; Al ₂ O _{3 the} rest. 11. 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 11-15%, copper oxide 8-21%, graphite 0-4%, oxide chromium (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 N-alkylation process is carried out in the presence of triethylamine in a molar ratio to para-nitrophenetole or para-phenethidine 0-0.1: 1.