JPS6232189B2 - - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a process for producing 2,3:5,6-bis(cycloalkeno)-pyridine. This substituted pyridine is an important intermediate for the production of pharmaceuticals, plant protection agents and plastics.

Suitable bis(2-oxo-cycloalkyl)-
It is known that 2,3:5,6-bis(cycloalkeno)-pyridine is obtained when methane and ammonium acetate are reacted. It is also known that bis(2-oxo-cycloalkyl)-methane is first converted into an oxime or semicarbazone, which is then hydrolyzed with acid to give 2,3:5,6-bis(cycloalkeno)-pyridine. (Bull.soc.chim.France vol. 5 (1957), 447-449
(see page). This bis-(2-oxo-cycloalkyl)-methane can be obtained by condensing the corresponding cycloalkanone with formaldehyde or by condensing the corresponding cycloalkanone with morpholine to obtain an enamine, which is then reacted with formaldehyde. (Ber.95 (1962) 1495
(See pages ~1504).

Furthermore, 2,3:5,6-bis(cycloalkeno)-pyridine can be synthesized by the reaction of a cycloalkanone with the corresponding hydroxymethylene-cycloalkanone and perchloric acid and the resulting 2,3:5,6-bis(cycloalkeno)-pyridine. )-pyrylium-perchlorate is known to be produced by treating it with ammonia (see Zhurnal Organ. Khim. Vol. 2 (1966), pp. 1864-1869). Furthermore, it is known that 2,3:5,6-bis(cycloalkeno)-pyridine is formed when cycloalkanones are heated in hexamethylphosphoric triamide.
From the alkyl-substituted cycloalkanone, the corresponding alkyl-substituted 2,3 in a similar manner:
5,6-bis(cycloalkeno)-pyridine is produced (Tetrahedron Letters Vol. 10 (1972) 929
(See pages ~932).

These known methods are not suitable for use on an industrial scale. These are expensive, cumbersome to handle and give only poor yields.

By the way, 2,3 from cycloalkanone:
A process for the preparation of 5,6-bis(cycloalkeno)-pyridine has been discovered, which involves combining a cycloalkanone having at least one reactive methylene group adjacent to the keto group with an aliphatic aldehyde and ammonia in the gas phase. Due to the presence of a catalyst that performs dehydration and dehydrogenation,
It consists of reacting at a temperature of about 250-550°C.
In this method, 2,3:5,6-bis(cycloalkeno)-pyridine is obtained from simple and readily available materials in a one-step reaction. This method, in contrast to the known methods, is highly suitable for use on an industrial scale.

According to the invention, the general formula: [In the formula, Z represents an aliphatic chain having 3 to 10 carbon atoms which may be substituted with a methyl group] A cycloalkanone of the general formula: O=CH-R () [In the formula, R is hydrogen or represents a branched alkyl group having 1 to 6 carbon atoms, especially an alkyl group having 1 to 2 carbon atoms] and ammonia to form a compound of the general formula: [In the formula, Z and R represent the above-mentioned compounds].

Examples of cycloalkanones () include: cyclobutanone, 3,5,5-
Trimethylcyclohexanone, cyclooctanone, cyclodecanone, 2-methylcyclohexanone, 3-methylcyclohexanone, 4-methylcyclohexanone, 2,2,4-trimethylcyclopentanone and especially cyclopentanone, cyclohexanone, cycloheptanone and cyclododecanone .

Examples of suitable aldehydes () are: propionaldehyde, butyraldehyde,
Isobutyraldehyde, acetaldehyde and especially formaldehyde.

The starting materials are optionally used as solutions, for example in water or lower alcohols such as methanol, ethanol and propanol (2). Ketones and aldehydes are also used in the form of substances from which they are liberated under the reaction conditions, for example as semi-acetals, as well as aldehydes as polymers, such as polyformaldehyde or formaldehyde as trioxane.

The reaction conditions, such as temperature and pressure and the quantity ratios of the reactants and the residence time, are optionally interrelated within certain ranges and are optionally dependent on the type of reactants and the type of catalyst.

Generally, this reaction is carried out at a temperature of about 250-550°C. In most cases about 300-500℃, especially 350℃
Temperatures of ~450°C are advantageous. It is advantageous to operate at pressures of about 1 to 4 bar, but lower or higher pressures can also be used. However, in order to use simple equipment, it is advantageous not to use too uneven a pressure.

The quantitative ratio of cycloalkanone () to aldehyde () can be broadly arbitrary and can be selected to be stoichiometric, lower or higher. It is generally advantageous to use about 0.2 to 2.0 moles of aldehyde () per mole of cycloalkanone (). Approximately 0.3 to 1.0, especially 0.4 to 0.8 mol of aldehyde () per mole of cycloalkanone () is preferred.

Ammonia can optionally be present in this reaction in a wide range from substoichiometric to superstoichiometric amounts.
In most cases, it will be advantageous to have at least 0.5 moles and up to about 100 moles of ammonia per mole of cycloalkanone (). Approximately 1 to 20 moles of ammonia per each mole of cycloalkanone (), preferably 2 to 20 moles of ammonia
15 mol, especially 3 to 12 mol, is preferred.

The reaction is carried out in the gas phase. The starting materials, which are optionally present in other states, are first converted into gaseous form. It is advantageous to use a gas consisting of a cycloalkanone (), an aldehyde () and ammonia diluted with an inert gas. Suitable inert gases are, for example, water vapor, air and, in particular, nitrogen. If the starting materials are used in the form of a solution, a gas diluted with a solvent is formed. Generally, a total of 20 moles or less of inert gas per mole of cycloalkanone (),
Preferably about 0.5 to 10 mol, especially 5 mol, are present.

Substances that have dehydration and dehydrogenation effects as catalysts fall under this category. This includes, for example, hydrocarbon processing.
47 (1968), pages 103-107, based on aluminum compounds such as aluminum oxide and aluminum silicate, optionally with additives of other metal oxides and fluorides. Advantageously, West German Patent Application Publication No. 2151417
Catalysts produced by the methods described in Japanese Patent No. 2224160 and Japanese Patent No. 2239801 are used. these are,
The composition comprises a composition treated at a temperature of about 550 to 1200°C containing the elements Al, F and O, and additionally a Si and Mg (in which case the atomic ratio Al to F is 1000
The ratio is 25 to 1000 to 800, and the atomic ratio is Al to Si and
Mg is 1000:5 to 1000:200) or b Ma and Ti (in this case the atomic ratio Al to F is 1000
vs. 10 to 1000 vs. 800, and the atomic ratio Al vs. Mg vs.
Ti is 1000:5 to 1000:200) or c Mg (in this case the atomic ratio Al to F is 1000:10 to
The ratio is 1000 to 800, and the atomic ratio Al to Mg is 1000 to 5.
~1000:200). These catalysts are used in fixed beds or especially in fluidized beds. This is generally about
Obtained with retention time of 0.2 to 5.0 seconds.

The gas mixture produced during the reaction can be worked up in a conventional manner by washing the gas with a liquid, in particular water or methanol,
Furthermore, separation by extraction and distillation can be carried out.

Particularly advantageously, West German Patent Application No. 2554946
The method described in that publication is used, in which the gas mixture is not washed but is cooled, with partial condensation leaving some excess ammonia in the residual gas, which is conducted directly into the circulation. be done.

Example 1 A fixed bed reactor with a content of 100 ml was charged with a catalyst having an atomic ratio of aluminum to magnesium to fluorine of 1000:25:50, prepared by the method described below.
49 g of cyclohexanone per hour on this catalyst
A gas mixture consisting of 25 g (0.25 mol) formaldehyde as a 30% aqueous solution, 44.8 Nl (2.0 mol) ammonia and 22.4 Nl (1.0 mol) nitrogen was introduced. The temperature in the reactor was maintained at 400°C. Cyclohexanone and formaldehyde were completely reacted. 17.8 g of 2,3:5,6-bis(cyclohexeno)-pyridine are obtained per hour,
This is 38% relative to the cyclohexanone used.
This corresponds to a yield of The product has a boiling point of 124-126℃/
2 mbar and had a melting point of 74° C. after recrystallization from petroleum ether.

The catalyst used in this example was prepared as follows: diameter 2 mm, length 4-6 mm and surface area 300 m ² /g.
(BET) aluminum oxide in the form of extrusions
1300 g of analytically pure magnesium nitrate hexahydrate [Mg
A solution of 160 g ( _0.62 mol) of (NO ₃ ) 2.6H ₂ O was added. The mixture was then dried by keeping it at 100° C. for 8 hours. The resulting dry material was stirred with a solution of 35.6 g (0.62 mol) of hydrofluoric ammonia in 1000 ml of water. The mixture was dried by keeping it at 100°C for 8 hours. The resulting dry material was stirred with a solution of 35.6 g (0.62 mol) ammonium hydrogen fluoride in 1000 ml water. The mixture was dried by keeping at 100°C for 12 hours. Continue drying the substance in a stream of air.
Heated at 700°C for 4 hours. The atomic ratio Al to Mg to F is
It was 1000 to 25 to 50.

The following example was carried out analogously to Example 1: Example 2 Starting materials: cyclododecanone, formaldehyde, ammonia and nitrogen; molar ratio 6:3
24:12 (formaldehyde is used as trioxane) Catalyst: Manufactured from aluminum oxide, magnesium nitrate, and titanium tetrafluoride by the method described below in an atomic ratio of aluminum:magnesium:titanium:fluorine: 1000:25:25:100 Reaction temperature: 420°C Conversion rate: 82% of cyclododecanone Product: 2,3:5,6-bis(cyclododeceno)-pyridine Melting point (after recrystallization from triol) 155°C Yield: Conversion rate: 82% of cyclododecanone The catalyst used in this example was prepared as follows: diameter 2 mm, length 4-6 mm and surface area (BET)
300m ² /g aluminum oxide in the form of extrusion moldings
1300 g of analytically pure magnesium nitrate hexahydrate [Mg
A solution of 160 g ( _0.62 mol) of (NO ₃ ) 2.6H ₂ O was added. The mixture was then dried by keeping it at 100° C. for 8 hours. The dry material was stirred with a solution of 77.5 g (0.62 mol) of titanium fluoride (TiF ₄ ) in 900 ml of water. The mixture was dried by keeping at 100°C for 12 hours. Continue drying the substance in a stream of air.
Heated at 700°C for 4 hours. Atomic ratio Al:Mg:
Ti:F was 1000:25:25:100.

Example 3 Extracting substances: cyclopentanone, formaldehyde, ammonia and nitrogen; molar ratio 2:1
8:4 (Formaldehyde is used as a mixture of 30% formaldehyde and 70% water) Catalyst: Aluminum oxide magnesium nitrate and fluorosilicic acid are prepared using the method described below in an atomic ratio of aluminum:magnesium:silicon:fluorine: 1000:24: Produced with 25:156 Reaction temperature: 390°C Conversion rate: 75% of cyclopentanone Product: 2,3:5,6-bis(cyclopenteno)-pyridine Melting point (after recrystallization from triol) 90°C Yield :2.7 for the cyclopentanone used
% The catalyst used in this example was prepared as follows: diameter 2 mm, length 4-6 mm and surface area (BET)
300m ² /g aluminum oxide in the form of an extrusion
1300 g of analytically pure magnesium nitrate hexahydrate [Mg
(NO ₃ ) ₂ ·6H ₂ O] and stirred under heat until all the liquid was absorbed. The material was kept at 100°C for 12 hours to dry. Continue with 400ml of water
Add a solution of 210 ml of 34% fluorosilicic acid in the solution and heat to 100 °C for 8 hours for drying, followed by drying in a stream of air.
It was held at 750°C for 4 hours.

Example 4 Starting materials: cycloheptanone, formaldehyde, ammonia and nitrogen; molar ratio 2:1
8:4 (formaldehyde is used as a mixture of 30% formaldehyde and 70% water) Catalyst: Same as Example 1 Reaction temperature: 400°C Conversion: 72% of cycloheptanone Product: 2,3:5, 6-Bis(cyclohepteno)-pyridine Melting point: 112°C Yield: 25% based on the cycloheptanone used Example 5 Starting materials: 2,4,4-trimethylcyclopentanone, formaldehyde, ammonia and nitrogen; molar ratio 2:1 8:4 (formaldehyde used as trioxane) Catalyst: Same as Example 1 Reaction temperature: 410°C Conversion: 65% of 2,4,4-trimethylcyclopentanone Product: 2,3:5,6- Bis(trimethylcyclopenteno)-pyridine, boiling point 94-96
°C/1 mbar Yield: 21% based on the 2,4,4-trimethylcyclopentanone used.

Example 6 Starting materials: cyclohexanone, propionaldehyde, ammonia and nitrogen; molar ratio 2:1:8:4 Catalyst: same as in Example 2 Reaction temperature: 410°C Conversion rate: 92% of cyclohexanone Product: 4-ethyl- 2,3,5,6-bis(cyclohexeno)-pyridine, boiling point 138~
142°C/1 mbar Yield: 36 based on the cyclohexanone used
% Example 7 Starting materials: cyclohexanone, acetaldehyde, ammonia and nitrogen; molar ratio 2:1
8 to 4 Catalyst: Same as Example 2 Reaction temperature: 410°C Conversion rate: 88% of cyclohexanone Product: 4-methyl-2,3,5,6-bis(cyclohexeno)pyridine, boiling point 132-135
°C/1 mbar Yield: 24 based on the cyclohexanone used
%

Claims (1)

[Claims] 1 General formula (): [In the formula, Z represents an aliphatic chain having 3 to 10 carbon atoms which may be substituted with a methyl group] and a cycloalkanone of the formula: O=CH-R () [In the formula, R is hydrogen or a branched an aliphatic aldehyde [representing an alkyl group having 1 to 6 carbon atoms] and ammonia at elevated temperature in a gas phase,
2,3:5,6 by catalytic reaction
-bis(cycloalkeno)-pyridine, wherein the reaction is carried out at a temperature of about 250-550°C in the presence of a catalyst, the catalyst comprising a composition treated with oxygen at a temperature of about 550-1200°C; The composition is
Al, F and O elements, and additionally a Si and Mg (in this case the atomic ratio Al to F is 1000
The ratio is 25 to 1000 to 800, and the atomic ratio is Al to Si and
Mg is 1000:5 to 1000:200) or b Mg and Ti (in this case the atomic ratio Al to F is 1000
vs. 10 to 1000 vs. 800, and the atomic ratio Al vs. Mg vs.
Ti is 1000:5 to 1000:200) or c Mg (in this case the atomic ratio Al to F is 1000:10 to
The ratio is 1000 to 800, and the atomic ratio Al to Mg is 1000 to 5.
~1000:200). 2. Carry out the reaction at a temperature of about 300-500°C. A method according to claim 1. 3. The method according to claim 1 or 2, wherein about 0.2 to 2.0 moles of aldehyde () are used per mole of cycloalkanone (). 4. A process according to any one of claims 1 to 3, wherein about 1 to 20 moles of ammonia are present per mole of cycloalkanone (). 5 Claim 1 introducing an inert gas
The method described in any one of paragraphs to paragraphs 4 to 4.