JPH11343273A - Production of cyanobenzaldehyde - Google Patents

Abstract

PROBLEM TO BE SOLVED: To industrially advantageously obtain a high purity cyanobenzaldehyde at high yield by reacting a specific cyanobenzylamine with ammonia and formaldehyde under an acidic condition. SOLUTION: The purpose of this invention is achieved by reacting (A) a cyanobenzylamine of formula I [CH2 NH2 group is located at meta- or para- position to cyano group; X is Cl or F; (n) is 0-4], (pref. p-cyanobenzylamine) with (B) ammonia and (C) formaldehyde or (D) a condensation product (pref. hexamethylenetetramine) of ammonia with formaldehyde in the presence of water under an acidic condition (pref. at pH 1.5-6.5) at pref. 70-130 deg.C for 30 min-10 h to obtain the objective compound of formula II (CHO group is located at meta or para-position to cyano group), (pref. p-cyanobenzaldehyde).

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a method for producing a cyanobenzaldehyde compound represented by the general formula (II).
A cyanobenzaldehyde compound is a compound useful as an intermediate of a medicine, an agricultural chemical, a liquid crystal, a functional polymer monomer and the like.

[0002]

2. Description of the Related Art Several methods for producing cyanobenzaldehyde compounds have been known for a long time. Here, a method for producing p-cyanobenzaldehyde will be described as a typical example. p-Cyanobenzaldehyde classically converts p-cyanobenzoic acid to p-cyanobenzoyl chloride with a chlorinating agent such as thionyl chloride and converts it to rosemund (R
o semund) reduction [Raport et al. , J. et al. Am. Che
m. Soc. , 75 (1953), 1125]. Also,
There is a method in which p-bromomethylbenzonitrile is reacted with hexamethylenetetramine in chloroform, and then the precipitated salt is thermally decomposed with an acetic acid-water solvent [Dyer e.
t al. , J. et al. Chem. Soc. , (1952) 4
778]. As a modification of this, a method of reacting p-chloromethylbenzonitrile with hexamethylenetetramine in an oil-water two-layer system (Japanese Patent Application Laid-Open No. 60-166655) is also known. Further, p-cyanobenzylamine is
Electrooxidation using 2,2,6,6-tetramethylpiperidinyl-1-oxide as mediator in the presence of 6-lutidine and perchlorate [Semmelhack e
t al. , J. et al. Am. Chem. Soc. , 105
(1983) 6732].

[0003]

As described above, as a problem of the method for synthesizing p-cyanobenzaldehyde, in the Rosemund reduction method, the synthesis of p-cyanobenzoic acid as a raw material requires multiple steps and is difficult to obtain. Further, in the method using p-halogenomethylbenzonitrile as a raw material, it is difficult to obtain p-tolunitrile as a raw material, and it requires a stoichiometric amount or more of hexamethylenetetramine. There is. Further, in the electrolytic oxidation of p-cyanobenzylamine, there is a problem that an tertiary amine is required to be 8 times in amount, and an oxidation mediator is required in an amount of 20% mol, and is decomposed as the reaction proceeds. Not suitable as a method.

[0004] As described above, p-cyanobenzaldehyde has a problem that the synthesis is complicated by conventionally known techniques, it is difficult to obtain a high-purity form, and it is not easy to obtain a raw material. Therefore, an object of the present invention is to produce a cyanobenzaldehyde compound of the general formula (II) in a high yield and a high purity by an industrially advantageous method. It is to produce m-cyanobenzaldehyde with high purity and high yield.

[0005]

Means for Solving the Problems The present inventor has used a benzylamine compound represented by the general formula (I) as a starting material, without damaging a cyano group which is a substituent on a benzene ring, without deteriorating an aminomethyl group (-CH ₂ NH _2). Was converted to an aldehyde group, thereby achieving the above object. That is, the present invention relates to the following inventions.

(1) The following general formula (I)

Embedded image (Wherein —CH ₂ NH ₂ is at the meta or para position of the cyano group, X represents a chlorine atom or a fluorine atom, n
Represents an integer of 0 to 4, and when n is 2 or more, Xs may be the same or different. Wherein the cyanobenzylamine compound represented by the general formula (II) is reacted under acidic conditions in the presence of ammonia and formaldehyde, or a condensate thereof and water.

Embedded image (Wherein -CHO is at the meta or para position of the cyano group, and X and n are the same as those described above).

(2) The method for producing a cyanobenzaldehyde compound according to the above (1), wherein the reaction is carried out in a mixed solvent of water and an organic solvent. (3) The method for producing a cyanobenzaldehyde compound according to the above (1) or (2), wherein the reaction is carried out in a pH range of 1.5 to 6.5. (4) The method for producing a cyanobenzaldehyde compound according to the above (1) to (3), wherein the condensate of ammonia and formaldehyde is hexamethylenetetramine. (5) The method for producing a cyanobenzaldehyde compound according to any one of (1) to (4), wherein the cyanobenzylamine compound is p- or m-cyanobenzylamine, and the cyanobenzaldehyde compound is p- or m-cyanobenzaldehyde.

[0008]

BEST MODE FOR CARRYING OUT THE INVENTION In the reaction of the present invention, a cyanobenzylamine compound, ammonia and formaldehyde, or a condensate thereof (such as hexamethylenetetramine) are charged into a reaction vessel under acidic conditions in the presence of water, and the reaction is carried out with stirring. This is carried out by raising the temperature, heating and stirring for a predetermined time. The charging and reaction of the reaction raw materials can be performed under pressure or under atmospheric pressure. Glass and acid-resistant metal containers are suitable as reactors.

[0009] Regarding the presumed reaction mechanism of the present invention, p-
The reaction from cyanobenzylamine to p-cyanobenzaldehyde will be described as an example. Known literature (Organi
cReaction, 8 (1954), 197), the elementary reaction is that an oxidation-reduction reaction occurs between an imine compound (formula 1) dehydrated and condensed from formaldehyde and ammonia and p-cyanobenzylamine, and methylamine and p-Cyanobenzylimine is formed (Formula 2). p-Cyanobenzylimine is hydrolyzed with an acidic aqueous solvent to form p-cyanobenzaldehyde (Formula 3).
The net response is (Equation 4).

[0010]

Embedded image

On the other hand, a typical dehydration condensation compound of ammonia and formaldehyde is hexamethylenetetramine (formula 5).

Embedded image The following theory has been considered as a mechanism for forming hexamethylenetetramine [Bose, J. et al. Ind. Che
m. Soc. , 34 (1957), 663] (Equation 6).
In the formula 6, the molecular formula N ₄ (CH ₂ ) ₆ is hexamethylenetetramine.

[0012]

Embedded image

As the ammonia, a compound that releases ammonia under the reaction conditions can be used even if it is other than the ammonia molecule itself, and formaldehyde is a compound that releases formaldehyde under the reaction condition even if it is other than the formaldehyde molecule itself. Can be used.

The cyanobenzylamine compound used in the present reaction will be described. Unsubstituted cyanobenzylamine compounds that can be suitably used include p-cyanobenzylamine and m-cyanobenzylamine, and the reduction reaction of one-side nitrile group of terephthalonitrile and isophthalonitrile (JP-A-49-85041). Gazette). Next, the cyanobenzylamine compound substituted with halogen will be described. 4-cyano-
Chlorinated cyanobenzylamine compounds such as 2,3,5,6-tetrachlorobenzylamine and 3-cyano-2,4,5,6-tetrachlorobenzylamine are obtained by chlorination of terephthalonitrile and isophthalonitrile. The chlorinated terephthalonitrile compound such as tetrachloroterephthalonitrile and the chlorinated isophthalonitrile compound such as tetrachloroisophthalonitrile can be easily synthesized by a reduction reaction of one side nitrile group. 4-cyano-
2,3,5,6-tetrafluorobenzylamine, 3-
The fluorinated cyanobenzylamine compounds such as cyano-2,4,5,6-tetrafluorobenzylamine are the tetrafluoroterephthalonitriles obtained by the fluorination reaction of the above chlorinated terephthalonitrile compounds and chlorinated isophthalonitrile compounds And a fluorinated isophthalonitrile compound such as tetrafluoroisophthalonitrile.

The reaction of the present invention requires the presence of ammonia and formaldehyde or a condensate of ammonia and formaldehyde such as hexamethylenetetramine. As the unmore, ammonia as a gas and aqueous ammonia as an aqueous solution can be used, and organic and inorganic salts such as ammonium acetate and ammonium carbonate which can release ammonia under the reaction conditions can be used. As formaldehyde, formaldehyde as a gas, formalin as an aqueous solution,
A dehydration condensate such as paraformaldehyde that can release formaldehyde under the reaction conditions, or an acetal of formaldehyde such as formaldehyde dimethyl acetal can be used.

The amount of ammonia used in the present invention is preferably 1 to 8 in a molar ratio to the cyanobenzylamine compound. The amount of formaldehyde used in the present invention is 1 to 1 in terms of a molar ratio with respect to the cyanobenzylamine compound.
12 is preferred. When the amount of ammonia or formaldehyde is too small with respect to the amount of the cyanobenzylamine compound, it takes time to complete the reaction. Conversely, when the amount is too large, large amounts of organic and inorganic compounds produced as a result of the reaction are produced. In the case of a condensate of ammonia and formaldehyde, the condensate of 1 mol of formaldehyde preferably has a molar ratio of 1 to 12 with respect to the cyanobenzylamine compound. In the case of hexamethylenetetramine which can be suitably used in the present invention, the molar ratio is 0.5 to the cyanobenzylamine compound.
To 2, preferably 0.7 to 1.3. When the amount of hexamethylenetetramine is too small with respect to the amount of the cyanobenzylamine compound, it takes time to complete the reaction, while when it is too large, it is difficult to separate the compound resulting from the reaction. In this reaction, water is used. Water may be used as a solvent or in trace amounts.

This reaction is carried out under acidic conditions. The acids used are organic or inorganic protic acids. As the inorganic acid, sulfuric acid, nitric acid, hydrochloric acid, phosphoric acid, and the like are preferable. As the organic acid, a carboxylic acid such as acetic acid or butyric acid, or a sulfonic acid such as tosylic acid can be used, and a carboxylic acid having a low boiling point, which can also serve as a solvent, is particularly preferable. Further, a Lewis acid such as aluminum chloride or stannic chloride which can react with a protic solvent to release a protonic acid can be used.

In this reaction, pH is important. Generally, a cyanobenzaldehyde compound is provided when the liquidity of the reaction mixture is weakly acidic. When the acidity is strongly acidic (pH <1), the yield of the cyanobenzaldehyde compound is extremely reduced. When the acidity is alkaline (pH> 8), the desired reaction does not usually occur, and almost no cyanobenzaldehyde compound is obtained. pH = 1.5
It is preferable to carry out the reaction under the conditions of -6.5.

This reaction can be carried out with an acidic aqueous solution. In addition, when the reaction is made with water alone,
Since an intermediate, a product, and the like may be precipitated, an organic solvent can be mixed and used to prevent the precipitation of the raw material, the product, and the like. For example, hydrocarbons such as toluene and xylene, alcohols such as methanol and ethanol, carboxylic acids such as acetic acid and propionic acid, halogens such as chloroform and 1,2-dichloroethane, nitriles such as acetonitrile and propionitrile And dioxane, 1,2-dimethoxyethane, and other ether-based organic solvents. The reaction may be performed by adding acetic acid or ethanol to make a homogeneous solution, or may be performed in a two-layer system using toluene or 1,2-dichloroethane. The solvent may be selected according to the purification method. The amount of the solvent in this reaction is preferably 3 to 10 times, and more preferably 4 to 6 times the total weight of the cyanobenzylamine compound and ammonia, formaldehyde or a condensate thereof (such as hexamethylenetetramine). If the reaction temperature is too low, the reaction rate is slow, and if it is too high, the generated cyanobenzaldehyde compound is decomposed and the yield becomes low, so the temperature is preferably 50 ° C to 150 ° C, more preferably 70 ° C to 130 ° C. It is desirable to select
The reaction time of this reaction depends on the reaction temperature and the composition of the solvent.
30 minutes to 10 hours are preferred.

[0020]

The present invention will be described in more detail with reference to the following examples, but the present invention is not limited to these examples. The reaction yield in the examples is based on the cyanobenzylamine compound.

Example 1 p-cyanobenzylamine 1
The solvent was adjusted to pH = 3 with 3 g, a 35% formalin aqueous solution 51 g, a 28% ammore aqueous solution 24 g, and sulfuric acid, and reacted at 90 ° C. for 2 hours while stirring. After cooling to room temperature, the mixture was ice-cooled for 2 hours. The precipitated crystals were collected by filtration, washed with water and dried, and 5.2 g of p-cyanobenzaldehyde (yield 40)
%). The purity of p-cyanobenzaldehyde obtained by high-performance liquid chromatography analysis was 99.5% or more. 5. High-performance liquid chromatographic analysis conditions (purity is measured under the same conditions as described below) Column: Shodex DE-513L + precolumn Eluent: water / acetonitrile / acetic acid = 2250/750/15 (ml) Sodium 1-octanesulfonate 45g Condition: Flow rate 1ml / min, UV254nm Column oven 40 ℃

Example 2 p-Cyanobenzylamine 4
0 g, hexamethylenetetramine 42 g, water 200 m
l, 200 ml of acetic acid, and 100 ° C. while stirring.
For 2 hours. After standing at room temperature overnight, flaky crystals precipitated. The precipitated crystals were collected by filtration, washed with water and dried, and 24.7 g of p-cyanobenzaldehyde (62% yield).
I got Purity was over 99%.

Example 3 p-cyanobenzylamine 5
6.2 g, 59.6 g of hexamethylenetetramine, water 4
6 ml, acetic acid 320 ml, 98% sulfuric acid 46 g were mixed,
The reaction was carried out at 100 ° C. for 2 hours while stirring. The reaction solution was concentrated to about half the volume by an evaporator, and the same amount of water as the distilled solvent was added to precipitate crystals. The precipitated crystals were collected by filtration, washed with water and dried to obtain p-cyanobenzaldehyde.
8 g (78% yield) was obtained. Purity was over 99%.

Example 4 p-Cyanobenzylamine 4
0 g, hexamethylenetetramine 42 g, water 400 ml
Was mixed, the solvent was adjusted to pH = 2.5 with sulfuric acid, and reacted at 90 ° C. for 2 hours with stirring. After cooling to room temperature, the mixture was cooled on ice, and the precipitated crystals were collected by filtration, washed with water, and dried.
-Cyanobenzaldehyde (13.2 g, yield 33%) was obtained. Purity was over 99%.

Example 5 p-cyanobenzylamine 4
0 g, hexamethylenetetramine 21 g, water 150 m
l, 150 ml of acetic acid mixed at 100 ° C. while stirring.
For 2 hours. The reaction solution was concentrated to half the volume with an evaporator, and the same amount of water as the distilled solvent was added to precipitate crystals. The precipitated crystals were collected by filtration, washed with water and dried to obtain 32.8 g (yield: 82%) of p-cyanobenzaldehyde. Purity was over 99%.

Example 6 8.0 g of p-cyanobenzylamine, 8.4 g of hexamethylenetetramine, 40 g of water
Then, 20 ml of acetic acid and 50 ml of toluene were mixed and reacted at 90 ° C. for 2 hours while stirring. After cooling to room temperature
The toluene layer was separated, washed with water, and the obtained toluene layer was concentrated until crystals were deposited. Water was added to the concentrated toluene solvent, and the toluene was azeotropically distilled off, followed by cooling to room temperature.
The precipitated crystals were collected by filtration, washed with water and dried to obtain 4.8 g (yield: 60%) of p-cyanobenzaldehyde.

Example 7 4.0 g of p-cyanobenzylamine, 4.2 g of hexamethylenetetramine, 15 ml of methanol, 15 ml of water and 8 ml of acetic acid were mixed, and the solvent was adjusted to pH = 3 with sulfuric acid. 5 at 70 ° C
Allowed to react for hours. The reaction solution was concentrated to half by an evaporator, and 20 ml of water was added to precipitate crystals. The precipitated crystals were collected by filtration, washed with water and dried to obtain 1.8 g of p-cyanobenzaldehyde (yield: 45%).

Example 8 p-Cyanobenzylamine 1
3 g, 12 g of paraformaldehyde, 46 g of ammonium acetate, 60 ml of water and 60 ml of acetic acid were mixed and reacted at 100 ° C. for 3 hours while stirring. The reaction solution was concentrated to half the volume with an evaporator, and the same amount of water as the distilled solvent was added to precipitate crystals. The precipitated crystals were collected by filtration, washed with water, and dried to obtain 8 g of p-cyanobenzaldehyde (yield: 62%).
%).

Example 9 p-cyanobenzylamine 1
3g, formaldehyde dimethyl acetal 30g, ammonium carbonate 38g, water 80ml, pH of the solvent with sulfuric acid
= 2.5, and reacted at 90 ° C. for 4 hours while stirring. After cooling to room temperature, the mixture was cooled on ice, and the precipitated crystals were collected by filtration, washed with water, and dried to obtain p-cyanobenzaldehyde.
1 g (yield 39%) was obtained.

Example 10 8.0 g of m-cyanobenzylamine, 8.4 g of hexamethylenetetramine, 40 g of water
and 40 ml of acetic acid, and 104 ° C. while stirring.
For 2 hours. After cooling to room temperature, 12 g of concentrated sulfuric acid was added. The solvent was concentrated to dryness using an evaporator in a water bath at 70 ° C. The concentrated residue was separated with toluene / water, further washed with water, and the obtained toluene layer was concentrated until crystals were deposited. Water was added to the concentrated toluene solvent, and the toluene was azeotropically distilled off, followed by cooling to room temperature. The precipitated crystals were collected by filtration, washed with water, and dried to obtain 5.9 g of m-cyanobenzaldehyde (yield 7).
4%). Purity was over 99%.

Example 11 13 g of m-cyanobenzylamine, 51 g of a 35% aqueous solution of formalin, 24 g of a 28% aqueous solution of ammore and 50 ml of acetic acid were mixed and reacted at 100 ° C. for 3 hours with stirring. After the reaction solution was concentrated to dryness using an evaporator, 100 ml of water was added to precipitate crystals. The precipitated crystals were collected by filtration, washed with water and dried to obtain 7 g of m-cyanobenzaldehyde (yield 54%). Purity was over 99%.

[0032]

According to the present invention, it is possible to easily produce a cyanobenzaldehyde compound with good yield and purity from a cyanobenzylamine compound easily obtained from m and p-phthalonitrile compounds and inexpensive animonia and formaldehyde or a condensate thereof. Can be. In particular, m- and p
-Cyanobenzaldehyde can be advantageously obtained.

Claims (5)

[Claims] 1. A compound represented by the following general formula (I): (Wherein —CH ₂ NH ₂ is at the meta or para position of the cyano group, X represents a chlorine atom or a fluorine atom, n
Represents an integer of 0 to 4, and when n is 2 or more, Xs may be the same or different. Wherein the cyanobenzylamine compound represented by formula (II) is reacted under acidic conditions in the presence of ammonia and formaldehyde, or a condensate thereof, and water. (Wherein -CHO is at the meta or para position of the cyano group, and X and n are the same as those described above). 2. The method for producing a cyanobenzaldehyde compound according to claim 1, wherein the reaction is carried out in a mixed solvent of water and an organic solvent. 3. The process for producing a cyanobenzaldehyde compound according to claim 1, wherein the reaction is carried out at a pH in the range of 1.5 to 6.5. 4. The process for producing a cyanobenzaldehyde compound according to claim 1, wherein the condensate of ammonia and formaldehyde is hexamethylenetetramine. 5. The method according to claim 1, wherein the cyanobenzylamine compound is p- or m-cyanobenzylamine, and the cyanobenzaldehyde compound is p- or m-cyanobenzaldehyde.