JPH0269462A - Production of cyano-phenylpyridines - Google Patents

Abstract

PURPOSE:To efficiently and safely obtain the subject compounds which are an intermediate for medicines, agricultural chemicals and dyes through reaction in one stage by reacting alkyl-substituted phenylpyridines as a raw material with ammonia and molecular oxygen in the presence of a catalyst. CONSTITUTION:Alkyl-substituted phenylpyridines expressed by formula I (R is 1-3C alkyl) are reacted with ammonia and molecular oxygen at a molar ratio of the ammonia and molecular oxygen within the range of 1:(1-50):(1.5-25) based on 1mol compound expressed by formula I, more preferably using an inert gas, such as nitrogen, as a diluent in the presence of a catalyst at 200-700 deg.C, preferably 300-500 deg.C to afford compounds expressed by formula II. A catalyst containing vanadium, alkaline metal and/or alkaline earth metal, oxygen and tin, titanium, chromium, etc., as an optional constituent element is used as the catalyst.

Description

Detailed Description of the Invention [Industrial Application Field] The present invention provides a method for producing cyano-phenylpyridines useful as pharmaceutical intermediates, agricultural chemical intermediates, dye intermediates, etc. This invention relates to a method for producing ammonia and molecular oxygen by subjecting them to a gas phase catalytic reaction in the presence of a catalyst.

[Conventional technology]

As a method for producing cyano-phenylpyridines, "
Chemical Abstracts, Volume 78.

58201t (1973) J discloses the cyanation of phenylpyridine.

[Problem to be solved by the invention]

The method for cyanating phenylpyridine is a three-step reaction in which phenylpyridine is first aminated with soda amide, then the amino group is exchanged with a bromine group using hydrogen bromide, and the bromine group is further exchanged with a cyano group using potassium ferricyanide. It takes. Furthermore, the sodaamide, hydrogen bromide and potassium ferricyanide used here are unstable substances or extremely toxic compounds and are very difficult to handle.

As described above, phenylpyridine is cyanated to produce cyanogen.
The method for producing phenylpyridines is an extremely disadvantageous method for industrial production.

The present invention was made to solve the above problems, and its purpose is to safely produce cyano-phenylpyridines in a single-stage reaction.

[Means to solve the problem]

The present inventors focused on a method of producing cyano-phenylpyridines by the so-called ammoxidation method, which is a completely unknown method of reacting alkyl-substituted phenylpyridines with ammonia and molecular oxygen.
As a result of extensive research, the inventors discovered a method for easily producing cyano-phenylpyridines and completed the present invention.

That is, the present invention provides an alkyl-substituted phenylpyrylene compound of general formula (I): (wherein, the kyl group) in the presence of gins, formula (■): R is represented by Al having 1 to 3 carbon atoms; The present invention relates to a method for producing cyano-phenylpyridines, characterized by subjecting ammonia and molecular oxygen to a catalytic gas phase catalytic reaction.

〔Example〕

The alkyl-substituted phenylpyridines used in the present invention have the general formula (I): (wherein R is an alkyl group having 1 to 3 carbon atoms)
It is a compound represented by, and specific examples thereof include 2-phenyl-3-methylpyridine, 2-phenyl-4-methylpyridine, 2-phenyl-5-methylpyridine, 2-phenyl-6-methylpyridine, 2-phenyl-6-methylpyridine, Methyl-3-phenylpyridine, 3-phenyl-4-methylpyridine, 3-
Phenyl-5-methylpyridine, 3-phenyl-B-methylpyridine, 2-methyl-4-phenylpyridine, 3
Examples include -methyl-4-phenylpyridine and alkyl-substituted phenylpyridines in which the methyl group of these methyl-phenylpyridines is substituted with an ethyl group or a propyl group.

The catalyst used in the method of the present invention contains an alkali metal and/or alkaline earth metal and (C) oxygen as its constituent elements, and has a high yield and selectivity of the target product. It is a preferable catalyst in terms of properties. As the alkali metal, lithium, sodium, potassium, and cesium can be used, and as the alkaline earth metal, magnesium and calcium can be used, but sodium, potassium, and cesium are preferably used.

The catalyst comprises (J vanadium, Mt.) an alkali metal and/or an alkaline earth metal, (C) oxygen, and at least one optional constituent element selected from the group consisting of tin, titanium, chromium, boron, and iron. It is preferable to use a mixture containing certain elements, since the yield and selectivity tend to be improved compared to combinations of these arbitrary constituent elements.

The composition ratio (atomic ratio) of each element is as follows: Vl-<alkali metal and/or alkaline earth metal). , 1-2-(Sn, , TI, Cr5B 5re)
A range of is preferred. The composition ratio of oxygen is O~5, which is determined by the valences and composition ratios of other catalyst constituent elements.

Various methods can be used to produce the catalyst, and examples thereof will be explained below.

Various vanadium compounds, alkali metal compounds, alkaline earth metal compounds, tin compounds, titanium compounds, chromium compounds and iron compounds are used as raw materials for the catalyst.

For example, vanadium compounds include vanadium pentoxide,
Ammonium metavanadate, vanadyl oxalate, etc.;
Alkali metal compounds and alkaline earth metal compounds include nitrates, sulfates, carbonates, etc. Tin compounds, titanium compounds, chromium compounds, and iron compounds include oxides, nitrates, sulfates, oxalates, etc.; boron compounds As the material, boric acid is preferably used, but it is not limited thereto.

adding an alkali metal compound and/or an alkaline earth metal compound to the aqueous solution containing the vanadium compound,
Furthermore, if necessary, at least one compound of an element selected from the group consisting of tin, titanium, chromium, boron and iron is added. Then, after adding nitric acid and stirring with heating, the pH is adjusted to around 5 using an ammonia aqueous solution. After evaporating to dryness, this is dried at a temperature of 100 to 300"C, preferably 150 to 250°C, and then fired in air at a firing temperature of 300 to 800°C, preferably 400 to 650°C, for 5 to 30 hours. The catalyst used in the present invention can be changed by calcining the catalyst in a .

The obtained catalyst can be used as it is, but it may also be supported on a carrier. When using a carrier,
After adding the carrier powder as it is or dispersing the carrier powder in water to a mixed aqueous solution of catalyst raw materials, or after impregnating a granular or spherical carrier with a mixed aqueous solution of catalyst raw materials, the same procedure as above is carried out. It can be prepared by a method of firing under firing conditions.

Examples of carriers include silica, alumina, silica-alumina, carborundum, which are conventionally known as carriers for oxidation catalysts.
Celite etc. can be used.

The shape of the carrier supporting the catalyst may be columnar, granular, etc., and may be selected depending on the conditions of use. Moreover, it may be used in any desired size.

The ammoxidation reaction in the present invention is a method in which alkyl-substituted phenylpyridines, ammonia, and molecular oxygen are subjected to a gas phase catalytic reaction on the catalyst prepared by the above method.

Oxygen and air can be used as oxygen sources here.

The molar ratio of ammonia and molecular oxygen to 1 mole of the alkyl-substituted phenylpyridine is preferably 1:
1 to 50:L, 5 to 25:L, and an inert gas such as nitrogen or water vapor may be used as a diluent.

The contact time between the reaction gas and the catalyst is not particularly limited and can generally be set over a wide range, but preferably a space velocity of 4
00 to 3000 hr −1, more preferably 500
~2000 hr'. In addition, the reaction temperature is usually 200 to 700°C, preferably 300 to 600°C.
is within the range of This reaction is usually carried out under normal pressure,
It can also be carried out under reduced pressure or increased pressure.

The desired cyano-phenylpyridine can be extracted by cooling and/or absorbing the resulting reaction product gas in a suitable solvent and subjecting the obtained cooling liquid or absorption liquid to separation means such as distillation.

Hereinafter, the present invention will be explained in more detail with reference to Examples. In addition, the conversion rate, yield, and selectivity are calculated by the following formula.

Selectivity (%) Number of moles of cyano-phenylpyridines produced Number of moles of reacted alkyl-substituted phenylpyridines x 100 Number of moles of reacted alkyl-substituted phenylpyridines Conversion rate (%) - Alkyl-substituted phenylpyridines supplied Number of moles of cyano-phenylpyridine produced Yield (%) - Number of moles of alkyl-substituted phenylpyridine supplied x 100 In the following examples, air was used as molecular oxygen.

Example 1 30 g of ammonium metavanadate was added to 300 ml of hot water. In addition, 8.72g of sodium nitrate was added to the line for 30 minutes.
After stirring at 70°C for about 1 hour, 17.5 g of Celite (trade name, Kimitsu Pharmaceutical's reagent, Celite-535) was added and evaporated to dryness. After drying this at 150℃ for 5 hours, it was heated to 600℃ in air.
A catalyst was prepared by calcining for 6 hours. 10 of the obtained catalyst
m1 reaction tube was filled.

In this reaction tube, 2-phenyl-6-methylpyridine:ammonia:air (115 to 02) was added in a molar ratio of 1=30:
A raw material gas having a composition of 30 (6 for 02) was flowed at a space velocity of 900 hr 7', and the reaction was carried out at a reaction temperature of 430°C. The absorption liquid obtained by absorbing the reaction product gas into methanol for 10 minutes was analyzed by gas chromatography. The same applies to Examples 2 to 12.

The results are shown in Table 1.

Examples 2 to 5 In place of the sodium nitrate used in Example 1, 10.37 g of potassium nitrate and 20.08 g of cesium nitrate were used.

A catalyst was prepared in the same manner as in Example 1, except that 26.31 g of magnesium nitrate or 24.23 g of calcium nitrate were added, respectively, and the reaction was carried out at the temperatures shown in Table 1. The results are shown in Table 1.

Margin below C] Example 6 Add 30.0 ml of ammonium metavanadate to 300 ml of warm water.
After adding 28 g of tin oxide, 30 g of tin oxide and 2.94 g of lithium nitrate were added, and then concentrated nitric acid (67.5%
) and stirred at 80° C. for about 2 hours. Next, it was adjusted to p115 with a 28% ammonia aqueous solution and then evaporated to dryness. After drying this at 150℃ for 5 hours, in the air,
A catalyst was prepared by calcining at 450° C. for 8 hours. The obtained catalyst was filled into a 10 ml reaction tube.

A raw material gas having a molar ratio of 2-phenyl-6-methylpyridine:ammonia:air of 20:20 was flowed into this reaction tube at a space velocity of 800 hr', and the reaction temperature was 42.
The reaction was carried out at 0°C. The results are shown in Table 2.

Examples 7 and 8 Sodium nitrate was used in place of the lithium nitrate used in Example 68. A catalyst was prepared in the same manner as in Example 6 except that 17 g of cesium nitrate or 15.52 g of cesium nitrate was added, respectively, and the reaction was carried out at the temperatures shown in Table 2. The results are shown in Table 2.

[Margin below]

Example 9 A solution diagram showing 43.28 g of oxalic acid dissolved in 35 ml of water at 80-90°C and 17.29 g of vanadium pentoxide dissolved therein, and 71 g of oxalic acid dissolved in water gamt on a hot water bath.
．． Dissolve 26 g of chromic anhydride in this and 19.04 g of chromic anhydride.
A solution (B) was prepared by dissolving the following. This solution (
A) and (B), 5.87 g of boric acid and 350 ml of warm water.
Cesium nitrate 7.4
1 g was added and stirred. After evaporating this to dryness, 15
A catalyst was prepared by drying at 0°C for 5 hours, calcining in air at 250°C for 12 hours, and further calcining at 550''C for 12 hours.The obtained catalyst was packed into a 10ml reaction tube.

A raw material gas having a molar ratio of 2-phenyl-6-methylpyridine:ammonia:air of 1:30:30 was flowed into this reaction tube at a space velocity of 900 h r-1, and the reaction temperature was 4.
The reaction was carried out at 00°C. The results are shown in Table 3. Example IO After adding 40 t of ammonium metavanadate to 300 ml of water, 28.87 g of cesium nitrate and 1.0 g of boric acid were added.
06g, iron nitrate 1.38g and titanium dioxide 13.8g
Add 7 g, then add 40 g of concentrated nitric acid and heat to 80°.
The mixture was stirred at C for 2 hours. Next, the pH was adjusted to 5 with a 28% ammonia aqueous solution, and the mixture was evaporated to dryness. Heat this at 150°C for 5
After drying for an hour, the catalyst was calcined in air at 550°C for 5 hours to prepare a catalyst. The obtained catalyst was filled into a 10 ml reaction tube.

A raw material gas having a molar ratio of 2-phenyl-6-methylpyridine:ammonia:air of 1:20:20 was flowed into this reaction tube at a space velocity of 800 hr to 1, and the reaction temperature was 450 hr.
The reaction was carried out at °C. The results are shown in Table 3.

Example 11 After adding 30 g of ammonium metavanadate to 300 ml of water, 15.39 g of cesium nitrate and 8.0 g of boric acid were added.
10 g 5 tin oxide 29.74 g and titanium dioxide 1
5.77 g was added, and further 30 f of concentrated nitric acid was added, followed by stirring at 80°C for 2 hours. Next, the pH was adjusted to 5 with a 28% ammonia aqueous solution, and the mixture was evaporated to dryness. This at 150℃
After drying for 5 hours, the catalyst was calcined in air at 450°C for 8 hours to prepare a catalyst. The obtained catalyst was packed into a 1Qm1 reaction tube.

A raw material gas having a molar ratio of 2-phenyl-6-methylpyridine:ammonia:air of 1:20:20 was flowed into this reaction tube at a space velocity of 800 h r-1, and the reaction temperature was 4.
The reaction was carried out at 30°C. The results are shown in Table 3.

Example 12 Iron nitrate 15.94 was used instead of boric acid used in Example 11
A catalyst was prepared and a reaction was carried out in the same manner as in Example 11, except that g was added. The results are shown in Table 3.

[Margin below]

The results shown in Tables 1 to 3 show that 2-cyano-6-phenylpyridine was obtained with good yield and good selectivity.

〔Effect of the invention〕

According to the production method of the present invention, cyano-phenylpyrylidines useful as pharmaceutical intermediates, agricultural chemical intermediates, dye intermediates, etc. can be efficiently and safely produced in a single reaction.

Claims (1)

[Claims] 1 General formula (I): ▲There are numerical formulas, chemical formulas, tables, etc.▼(I) (In the formula, R is an alkyl group having 1 to 3 carbon atoms)
Formula (II) is characterized by causing an alkyl-substituted phenylpyridine represented by, ammonia and molecular oxygen to undergo a gas phase catalytic reaction in the presence of a catalyst: ▲There are mathematical formulas, chemical formulas, tables, etc.▼ (II) A method for producing cyano-phenylpyridines. 2. The method according to claim 1, wherein the catalyst contains (a) vanadium, (b) an alkali metal and/or an alkaline earth metal, and (c) oxygen as its constituent elements. 3. The catalyst contains at least one element selected from the group consisting of (a) vanadium, (b) alkali metals and/or alkaline earth metals, (c) tin, titanium, chromium, boron, and iron. 2. The method according to claim 1, comprising the element and (d) oxygen.