RU2227134C2 - Method for preparing substituted monocyclic ketones - Google Patents

Abstract

FIELD: organic chemistry, chemical technology. SUBSTANCE: invention relates to method for preparing substituted monocyclic C₄-C₂₀.-ketones. Method is based on reaction of liquid-phase oxidation of substituted monocyclic alkenes of the formula C_nH_(2n-2-m)R $\genfrac{}{}{0ex}{}{\text{i}}{\text{m}}$ wherein m has values from 4 to 20; n has value from 1 to (2n-2); Rⁱ means substituents in cycle that represent hydrogen atom, alkyl, alkenyl or aryl radicals, among them comprising functional groups, except for radicals that include non-aromatic carbo- or heterocycles having double bonds C=C with nitrous oxide in the presence of inert gas as a diluting agent at temperature 100-350 C and under pressure of nitrous oxide 1.5-100 atm. Process provides the high selectivity by end products, explosion- -proofing and shows outlook for industrial using. EFFECT: improved preparing method. 5 cl, 3 tbl, 26 ex

Description

The invention relates to a method for producing substituted monocyclic C ₄ -C ₂₀ ketones, and more particularly to a method for their preparation by liquid-phase oxidation with nitrous oxide (N ₂ O) of substituted monocyclic alkenes containing 4-20 carbon atoms in a ring.

Substituted monocyclic ketones C ₄ -C ₂₀ are the starting materials for the synthesis of various organic products, including synthetic polymeric materials, agrochemicals, pharmaceuticals, etc.

Several methods are known for preparing substituted monocyclic ketones. For example, liquid phase oxidation of alkyl substituted cycloalkanes with atmospheric oxygen is widely used for this purpose. The oxidation can be carried out both in the presence of a catalyst and without a catalyst. In both cases, a mixture of cyclic ketones and alcohols is formed as reaction products. For example, mono- and dialkyl-substituted cycloalkanes C ₅ -C _{8 are} oxidized non-catalytically to a mixture of the corresponding ketones and alcohols at a temperature of 150-210 ° C and a pressure of 3-40 atm. In the case of methylcyclohexane, a mixture of methylcyclohexanones and 3-methylcyclohexanol is formed, in which the proportion of ketones is about 50% [US Pat. No. 2,609,395, 1952, CFDoungherty et al.].

A mixture of alkyl substituted cyclic ketones and alcohols can also be obtained from the corresponding cycloalkenes using Co and Mn salts as a catalyst at 120-180 ° C and a pressure of 5-25 atm [US Pat. No. 2223494, 1940, J. Loder; US Pat. No. 3093686, 1963, W. Simon et al .; US Pat. No. 3917708, 1975, A. Kuessner et al.]. A common disadvantage of these methods is the formation, along with ketone, of a large amount of cyclic alcohol, as well as a significant decrease in the selectivity of the reaction with increasing conversion.

Alkyl substituted monocyclic ketones can also be obtained by decarboxylation and cyclization of alkyl substituted dicarboxylic acids [US Pat. 5600013, 1997, Alas et al.]. The process is carried out at 200-300 ° C, using metal phosphates of groups 1a, 2a or 3b of the groups of the periodic system of elements as catalysts. Thus, 2,2-dimethylcyclopentanone is formed from 2,2-dimethyladipic acid in the presence of sodium phosphate. In addition to the high cost of raw materials, the disadvantage of this method is the presence of an aggressive acidic environment at high temperature.

According to the patent [US Pat. No. 2863923, 1958, N. M. Bortnick] 2,5-dimethylcyclopentanone can be obtained by cyclization of 2,5-dimethyladipic acid esters at 350-600 ° C in the presence of Mn or Cd oxides. The disadvantage of this method is the need for an additional stage of obtaining esters, which complicates the technological scheme.

A known method of producing monocyclic ketones containing methyl groups in the α-position, by alkylation of the corresponding cyclic ketones with methanol at 350-500 ° C in the presence of Mn oxide [US Pat. No. 4618725, 1986, H. H. Lenz]. However, the selectivity of this reaction is not high enough.

In GB Pat. 649680 (1951) discloses a method for the oxidation of olefins to carbonyl compounds with nitrous oxide. According to this method, in particular, it is possible to obtain 2-methylcyclopentanone by oxidation of 1-methylcyclopentene, as well as 2-phenylcyclohexanone and cyclopentylphenylketone by oxidation of 1-phenylcyclohexene.

The main disadvantage of this method is the possibility of the formation of flammable mixtures of “cycloalkene - nitrous oxide” during the process. In order to eliminate the danger of explosion, the authors of the patent propose additionally introducing saturated hydrocarbons into the reaction mixture. However, later studies have shown that mixtures of saturated hydrocarbons with N ₂ O are as explosive as mixtures of olefins [G. Panetier, A. Sicard, V Symposium on Combustion, 620 (1955); B.B.Brandt, L.A. Matov, A.I. Rozlovsky, V.S. Khaylov, Chem. prom., 1960, No. 5, p. 67-73]. Therefore, saturated hydrocarbons, despite their lower reactivity, cannot serve as a means to exclude explosive hazards.

The present patent discloses a method for producing substituted monocyclic ketones by oxidizing substituted monocyclic alkenes with nitrous oxide, N ₂ O, in the presence of an inert gas that does not have these drawbacks. According to this method, the reaction is carried out in the presence of an inert gas under conditions where the cycloalkene is present in the form of a liquid phase in which the oxidation reaction proceeds with high selectivity. An excessive increase in temperature and / or pressure of N ₂ O is undesirable, as it can lead to a decrease in selectivity due to the contribution of gas-phase oxidation.

The composition of the starting substituted monocyclic alkenes is expressed by the formula

where R ⁱ are the same or different substituents in the cycle, n has values from 4 to 20, m has values from 1 to (2n-2). The substituents R ⁱ in the formula (I) can be represented by halogen atoms, alkyl, alkenyl, aryl or other inorganic or organic radicals, including those containing functional groups, in addition to radicals that include non-aromatic carbo- or heterocycles having double bonds C = C. For example, in the case of methylcyclohexene, the radical R ⁱ is represented by the group CH ₃ , n = 6, m = 1.

Explosion-proof working conditions of the proposed method are provided by adding to the reaction mixture an inert gas that does not react with N ₂ O, for example nitrogen, helium, argon, carbon dioxide, etc., or a mixture thereof. The role of an inert gas can play the reaction exhaust gases or recycle gases. At different stages of the process, depending on the cycloalkene: nitrous oxide ratio, the fraction of inert gas needed to ensure explosion-proof operation can be different and created by supplying it separately. From the point of view of simplicity and maximum safety of the process, it is advisable to have such a dilution of nitrous oxide with an inert gas so that the reaction mixture is non-explosive at any cycloalkene content. This condition is satisfied if the content of N ₂ O in the mixture with an inert gas is not more than 25%. The use of such a mixture eliminates the occurrence of explosive situations at all stages of the process.

To reduce the risk of explosion, flame retardants such as trifluorobromomethane, difluorochlorobromomethane, dibromotetrafluoroethane, etc. can be added to the reaction mixture.

In accordance with this invention, the oxidation of substituted monocyclic alkenes C ₄ -C ₂₀ into the corresponding cyclic ketones with nitrous oxide in the presence of an inert gas can be carried out in a wide range of conditions in both a static and a flow reactor, which can be made of steel, titanium, glass or other suitable material. In this case, all known technological methods that increase the efficiency of gas-liquid reactions can be used.

In the case of the static embodiment, cycloalkene is placed in the autoclave in such an amount that, when heated to the reaction temperature, it is present in the form of a liquid phase. Oxygen in the reactor is replaced with a mixture of nitrous oxide with an inert gas and the pressure is adjusted to a predetermined value. The amount of nitrous oxide is selected so that its pressure at the reaction temperature is 1.5-100 atm. The concentration of inert gas in a mixture with nitrous oxide is selected so that it does not exceed 99%. After that, the reactor is closed and heated to a reaction temperature in the range of 100-350 ° C. The reaction time is selected depending on the conditions of its implementation, as well as the requirements for the process, and can vary from several tens of minutes to several tens of hours.

The proposed process can be carried out without solvents. However, it is possible to carry out the process using solvents, which can be selected from a wide range of substances used in the practice of organic synthesis. The reaction proceeds at a fairly high rate without a catalyst, although it can be carried out in the presence of a catalyst.

The proposed method does not imply a high purity of the starting reagents. Thus, nitrous oxide can be used both in pure form and with impurities of various gases that do not adversely affect the performance of the process. Substituted monocyclic alkenes may also contain impurities of other organic compounds, especially if they do not contain double C = C bonds.

The essence of the invention is illustrated by the following examples.

Examples 1-2

Example 1. This example is comparative. 25 cm ^{3 of} 4-methyl-1-cyclohexene (Aldrich, 99%) are poured into a 100 cm ³ reactor made of stainless steel and equipped with a stirrer (Parr). The reactor is purged with nitrous oxide and then its pressure is adjusted to 10 atm. The reactor is hermetically sealed, heated to 220 ° C and maintained at this temperature for 12 hours. The nitrous oxide pressure at the reaction temperature is 30 atm. After the completion of the reaction, the reactor was cooled to room temperature and the final composition of the gas and liquid phases was analyzed by gas chromatography, chromatography-mass spectrometry, and NMR. From the obtained data, the conversion of 4-methyl-1-cyclohexene (X) and the selectivity of the reaction for the resulting products (S _i ) are calculated

- начальная концентрация 4-метил-1-циклогексена. В случае больших конверсии величина Х может быть рассчитана также по разнице между начальной и конечной концентрациями 4-метил-1-циклогексенаwhere C _i is the concentration of the i-th reaction product,

- initial concentration of 4-methyl-1-cyclohexene. In the case of large conversions, X can also be calculated from the difference between the initial and final concentrations of 4-methyl-1-cyclohexene

The main reaction products are 3-methylcyclohexanone and 4-methylcyclohexanone. In the table. 1 shows the total selectivity for 3- and 4-methylcyclohexanones, which are formed in approximately equal amounts.

Example 2 is similar to example 1 with the difference that instead of pure nitrous oxide, a mixture with an inert gas, nitrogen, in which the concentration of N ₂ O is 20%, is fed into the reactor (Table 1).

The initial pressure of the mixture in the reactor, P °, set to 90 ATM. The nitrous oxide pressure at the reaction temperature is 30 atm.

This example shows that the reaction of liquid-phase oxidation of substituted monocyclic alkenes into cyclic ketones proceeds while maintaining conversion and high selectivity when using a mixture of nitrous oxide with an inert gas as an oxidizing agent.

Examples 3-10

Examples 3-10 show the possibility of carrying out the reaction using mixtures of nitrous oxide with inert gases of various compositions (table 2).

Example 3 is similar to example 2 with the difference that a mixture of nitrous oxide with nitrogen is used for oxidation, in which the concentration of N ₂ O is 70%, and the initial pressure in the reactor is set to 80 atm. The experiment is carried out at 100 C for 90 hours. The pressure of N ₂ O at the reaction temperature is 100 atm.

Example 4 is similar to example 2 with the difference that for oxidation a mixture of nitrous oxide and nitrogen is used, in which the concentration of N ₂ O is 1%, nitrogen - 99%. The initial pressure of the mixture in the reactor is set to 100 atm. The experiment is carried out at 250 ° C for 24 hours. The pressure of N ₂ O at the reaction temperature is 1.5 atm.

Example 5 is similar to example 2 with the difference that for oxidation a mixture of nitrous oxide and nitrogen is used, in which the concentration of N ₂ O is 95%, nitrogen - 5%. The initial pressure of the mixture in the reactor is set to 28 atm. The experiment is carried out at 198 ° C for 15 hours. The pressure of N ₂ O at the reaction temperature is 70 atm.

Example 6 is similar to example 2 with the difference that the concentration of N ₂ O in the mixture with nitrogen is 70%, and the initial pressure of the mixture in the reactor is set to 45 atm. The experiment is carried out at 250 ° C for 5 hours. The pressure of N ₂ O at the reaction temperature is 77 atm.

Example 7 is similar to example 6 with the difference that the concentration of N ₂ O in the mixture is 20%. The experiment is carried out at 250 ° C for 12 hours. The pressure of N ₂ O at the reaction temperature is 15 atm.

Example 8 is similar to example 2 with the difference that a mixture of nitrous oxide with argon is used for oxidation, in which the concentration of N ₂ O is 50%. The initial pressure of the mixture in the reactor is set to 30 atm. The pressure of N ₂ O at the reaction temperature is 30 atm.

Example 9 is similar to example 8 with the difference that carbon dioxide is used instead of argon.

Example 10 is similar to example 7 with the difference that the experiment is carried out at 350 ° C for 2 hours. The pressure of N ₂ O at the reaction temperature is 20 ATM.

Example 11

This example is comparative. The experiment is carried out analogously to example 6 with the difference that 3 ml of 4-methyl-1-cyclohexene are loaded into the reactor. With this amount, all 4-methyl-1-cyclohexene is in the gas phase under the reaction conditions. The experiment is carried out at 250 ° C for 5 hours, using a mixture of nitrous oxide with nitrogen, in which the concentration of N ₂ O is 70%. The initial pressure of the mixture in the reactor is set at 45 atm. As a result of the experiment, the conversion of 4-methyl-1-cyclohexene was about 0.5%. This shows that under these conditions, the reaction in the gas phase practically does not occur.

Examples 12-13

Examples 12-13 (table 3) show the possibility of carrying out the process in the presence of a catalyst.

Example 12 is similar to example 5 with the difference that the oxidation of 4-methyl-1-cyclohexene is carried out in the presence of 0.5 g of Fe ₂ O ₃ / SiO ₂ (2.8 wt.% Fe ₂ O ₃ ). The catalyst is prepared by impregnating SiO ₂ with a solution of FeCl ₃ , dried at 110 ° C and calcined in air at 500 ° C for 2 hours. For oxidation, a mixture of nitrous oxide with nitrogen is used, in which the concentration of N ₂ O is 95%. The initial pressure of the mixture in the reactor is set to 28 atm. The experiment is carried out at 198 ° C for 15 hours. The pressure of N ₂ O at the reaction temperature is 70 atm.

Example 13 is similar to example 5 with the difference that the reaction is carried out in the presence of 0.3 g of Ag / SiO ₂ (1 wt.% Ag). The catalyst is prepared by impregnating SiO ₂ with an AgNO ₃ solution, dried at 110 ° C and calcined in air at 500 ° C for 2 hours.

Examples 14-15

These examples demonstrate the possibility of oxidizing 3-cyclohexen-1-yl-methanol and 5-methylcyclooctene-1 with nitrous oxide diluted with an inert gas, including using solvents.

Example 14 is similar to example 6 with the difference that 25 cm ^{3 of a} mixture of 3-cyclohexene-1-methanol and cyclohexane are poured into the reactor in a volume ratio of 1: 1, and the experiment is carried out at 150 ° C for 20 hours. For oxidation, a mixture of nitrous oxide with nitrogen is used, in which the concentration of N ₂ O is 70%. The initial pressure of the mixture in the reactor is set at 45 atm. The pressure of N ₂ O at the reaction temperature is 60 atm. The conversion of 3-cyclohexene-1-methanol is 2.5%. The reaction proceeds with the formation of 3-oxocyclohexyl-1-methanol and 4-oxocyclohexyl-1-methanol in a ratio close to 1: 1, with a total selectivity of more than 90%.

Example 15 is similar to example 6 with the difference that instead of 4-methyl-1-cyclohexene, 5-methyl-cyclooctene-1 is used, and the experiment is carried out at 198 ° C for 12 hours. The pressure of N ₂ O at the reaction temperature is 70 atm. The conversion of 5-methylcyclooctene-1 is 30.5%. The reaction produces 4-methylcyclooctanone and 5-methylcyclooctanone in a 1: 1 ratio with a total selectivity of 95%.

Examples 16-17

These examples demonstrate the possibility of oxidizing 1-methyl-1-cyclohexene with nitrous oxide diluted with an inert gas, including using solvents.

Example 16 is similar to example 6 with the difference that 25 cm ^{3 of} 1-methyl-1-cyclohexene (Aldrich, 99%) is poured into the reactor, and the experiment is carried out at 250 ° C. for 12 hours. For oxidation, a mixture of nitrous oxide with nitrogen is used, in which the concentration of N ₂ O is 70%. The initial pressure of the mixture in the reactor is set at 45 atm. The pressure of N ₂ O at the reaction temperature is 77 atm. The conversion of 1-methyl-1-cyclohexene is 35% with a total selectivity of 2-methylcyclohexanone and cyclopentylethanone (approximately 1: 1) 79%.

Example 17 is similar to example 16 with the difference that 70 cm ^{3 of a} mixture of 1-methyl-1-cyclohexene and toluene are poured into the reactor in a volume ratio of 1: 6. For oxidation, a mixture of nitrous oxide with nitrogen is used, in which the concentration of N ₂ O is 40%. The initial pressure of the mixture in the reactor is set at 40 atm. The pressure of N ₂ O at the reaction temperature is 38 atm. The conversion of 1-methyl-1-cyclohexene is 22% with a total selectivity of formation of 2-methylcyclohexanone and cyclopentylethanone of 80.3%.

Examples 18-26

These examples demonstrate the possibility of oxidation using nitrous oxide diluted with an inert gas, including using solvents, various substituted monocyclic alkenes, including halogen atoms, various functional groups, alkyl, alkenyl or aryl (including heterocyclic) radicals as substituents .

Example 18 is similar to example 6 with the difference that 25 cm ^{3 of} 1-methyl-1-cyclopentene are loaded into the reactor and the experiment is carried out at 198 ° C for 10 hours. For oxidation, a mixture of nitrous oxide with nitrogen is used, in which the concentration of N ₂ O is 70%. The initial pressure of the mixture in the reactor is set at 45 atm. The pressure of N ₂ O at the reaction temperature is 70 atm. As oxygen-containing products, 2-methylcyclopentanone and 1-hexene-5-non are formed in an approximate ratio of 1.5: 1 with a total selectivity of 86%. The conversion of 1-methyl-1-cyclopentene is 13.2%.

Example 19 is similar to example 6 with the difference that 25 cm of 3-bromocyclohexene are loaded into the reactor and the experiment is carried out at 198 ° C for 12 hours. For oxidation, a mixture of nitrous oxide with nitrogen is used, in which the concentration of N ₂ O is 70%. The initial pressure of the mixture in the reactor is set at 45 atm. The pressure of N ₂ O at the reaction temperature is 70 atm. As oxygen-containing products, 2-bromocyclohexanone and 3-bromocyclohexanone are formed in an approximate ratio of 1: 1 with a total selectivity of 84%. The conversion of 3-bromocyclohexene is 6%.

Example 20 is similar to example 19 with the difference that 25 cm ^{3 of} 3-cyclohexene-1-carboxaldehyde and benzene are loaded into the reactor in a volume ratio of 1: 1. The conversion of 3-cyclohexene-1-carboxaldehyde is 8.8% with a total selectivity of the formation of (cyclohexanon-3-yl) carboxaldehyde and (cyclohexanon-4-yl) carboxaldehyde 85.6%.

Example 21 is similar to example 19 with the difference that 25 cm ^{3 of} 3-cyclohexene-1-ol are charged into the reactor. As oxygen-containing products, 3-hydroxycyclohexanone and 4-hydroxycyclohexanone are formed in an approximate ratio of 1: 1 with a total selectivity of 84% for the conversion of 3-cyclohexene-1-ol 5.6%.

Example 22 is similar to example 19 with the difference that 25 cm ^{3 of} 4-vinylcyclohexene are charged into the reactor. As oxygen-containing products, 3-ethenyl-1-cyclohexanone, 4-ethenyl-1-cyclohexanone, 3-cyclohexene-1-carboxaldehyde, 1- (3-cyclohexen-1-yl) ethanone and 3-cyclohexene-1-acetaldehyde are formed with the total selectivity of 73% at the conversion of 4-vinylcyclohexene 10.5%.

Example 23 is similar to example 19 with the difference that 25 cm ^{3 of} 1,3,5-trimethyl-1-cyclohexene are charged into the reactor, and the experiment is carried out at 220 ° C. for 12 hours. The pressure of N ₂ O at the reaction temperature is 72 atm. As oxygen-containing products, 2,4,6-trimethylcyclohexanone and 1- (2,4-dimethyl) cyclopentylethanone are formed in an approximate ratio of 1.4: 1 with a total selectivity of 80.4% for the conversion of 1,3,5-trimethyl-1 - cyclohexene 17.5%.

Example 24 is similar to example 6 with the difference that 25 cm ^{3 of} 6-methyl-3-cyclohexene-1-methanol are charged into the reactor. For oxidation, a mixture of nitrous oxide with nitrogen is used, in which the concentration of N ₂ O is 70%. The initial pressure of the mixture in the reactor is set at 45 atm. The experiment is carried out at 250 ° C for 5 hours. The pressure of N ₂ O at the reaction temperature is 77 atm. The conversion of 6-methyl-3-cyclohexene-1-methanol is 16.7%. The reaction proceeds with the formation of 2-methyl-4-oxocyclohexyl-1-methanol and 2-methyl-5-oxocyclohexyl-1-methanol with a total selectivity of 75%.

Example 25 is similar to example 24 with the difference that 25 cm ^{3 of} 4- (3-cyclohexen-1-yl) pyridine are charged to the reactor. The conversion of 4- (3-cyclohexen-1-yl) pyridine is 15.7%. The reaction proceeds with the formation of 4- (3-cyclohexanon-1-yl) pyridine and 4- (4-cyclohexanon-1-yl) pyridine with a total selectivity of 97%.

Example 26 is similar to example 24 with the difference that 25 cm ^{3 of} 1-phenyl-1-cyclohexene are charged into the reactor. The conversion of 1-phenyl-1-cyclohexene is 12.6%. The reaction proceeds with the formation of 2-phenylcyclohexanone and cyclopentylphenylketone with a total selectivity of 91%.

Examples 2-10 and 12-26 show that substituted monocyclic alkenes are highly selectively oxidized to the corresponding ketones with nitrous oxide diluted with an inert gas. Carrying out the process without the use of an inert diluent gas leads to the formation of explosive cycloalkene-N ₂ O compositions in the gas phase when the reactor is filled with nitrous oxide, heated, or under reaction conditions. For example, carrying out the process of example 1 without adding inert gas leads to the formation of mixtures containing up to 15% of alkene vapor in nitrous oxide, the explosion hazard of which is described in [G. Panetier, A. Sicard, V Symposium on Combustion, 620 (1955); Bb Brandt, L.A. Matov, A.I. Rozlovsky, V.S. Khaylov, Chem. prom., 1960, No. 5, p. 67-73]. The process in similar conditions, but using a mixture of N ₂ O-inert gas, in which the concentration of N ₂ O is 20% (example 2), eliminates the formation of explosive mixtures and ensures the safety of the process.

According to the proposed method, the content of N ₂ O in an inert gas can vary over a wide range, including the range of nitrous oxide concentrations of 25% or less, which excludes the possibility of explosive situations at all stages of the process with any compositions with cycloalkene. As examples 2, 7 and 10 show, the oxidation reaction in this area proceeds with high efficiency.

The present invention provides a new method for producing substituted monocyclic ketones based on the liquid phase oxidation reaction of substituted monocyclic alkenes with a mixture of nitrous oxide and an inert gas. The process provides high selectivity, explosion safety and is promising for industrial applications.

Claims (5)

1. The method of obtaining substituted monocyclic ketones, carried out by contact with nitrous oxide in the liquid phase of substituted monocyclic alkenes of the formula

, where n has values from 4 to 20, m has values from 1 to (2n-2), where R ⁱ are substituents in the cycle that can be represented by halogen atoms, alkyl, alkenyl or aryl radicals, including those containing functional groups except radicals that include non-aromatic carbo- or heterocycles having C = C double bonds, characterized in that the reaction is carried out at a temperature of 100-350 ⁰ C and a pressure of N ₂ O from 1.5 to 100 atm in the presence of inert diluent gas. 2. The method according to claim 1, in which the concentration of inert gas in the reaction mixture does not exceed 99%. 3. The method according to any one of claims 1 and 2, in which the concentration of inert gas is selected so that the content of N ₂ O in the mixture with inert gas is not more than 25% to exclude the possibility of the formation of explosive compositions at all stages of the process. 4. The method according to any one of claims 1 to 3, in which the reaction is carried out in the presence of a catalyst. 5. The method according to any one of claims 1 to 4, in which the reaction is carried out in the presence of a solvent.