JPH05339191A - Production of aldehyde - Google Patents

Abstract

PURPOSE:To industrially advantageously obtain under mild conditions an aldehyde as an intermediate important in the organic synthesis dispensing with complicated operation or special condition by a specific means by using an aromatic ring- or heterocycle-substituted methanol as raw material. CONSTITUTION:Firstly, an aromatic ring-substituted methanol (e.g. 4- methylbenzyl alcohol) or heterocycle-substituted methanol (e.g. 2- thiophenemethanol) is made to react with hexamethylenetetramine and a haloiminum salt of the formula (R<1> and R<2> are each lower alkyl; X is halogen; n is 2 or 3) to form a hexaiminium salt, which is then hydrolyzed with an acid such as acetic acid to obtain the objective compound. The haloiminium salt is pref. 2-chloro-1,3-dimethylimidazolinium chloride. The above reaction between the methanol compound, hexamethylenetetramine and the compound of the formula is recommended to carry out in the presence of a base such as pyridine.

Description

Detailed Description of the Invention

[0001]

FIELD OF THE INVENTION The present invention relates to a method for producing aldehydes, which does not require complicated operations or special conditions.
The present invention relates to a method capable of industrially producing aromatic or heterocyclic aldehydes.

[0002]

Aldehydes are important intermediates in organic synthesis because they can be converted into halogen compounds, alcohols, carboxylic acids or nitrogen-containing compounds. Also,
Aldehydes are also important synthetic intermediates for pharmaceuticals, agricultural chemicals, etc., since they are used as constitutional units in heterocyclic compounds.

Conventionally, many methods for producing aldehydes have been reported, but among them, the method of converting primary alcohols into aldehydes by oxidation reaction is the most general and important production method. As a method for producing aldehydes, particularly aromatic or heterocyclic aldehydes, by the oxidation reaction of primary alcohols, chromic acid is used for oxidation, active manganese dioxide is used, trifluoroacetic anhydride or oxalyl chloride. A method using dimethyl sulfoxide activated by (Swern oxidation), a method using an oxoammonium salt, and the like are known.

[0004]

However, the method using chromic acid is not suitable for large-scale use in view of post-treatment because of the problem of environmental pollution due to the use of heavy metals. In addition, the method using active manganese dioxide requires that active manganese dioxide must be prepared from a manganese salt and potassium permanganate before use, needs to be used in large amounts in the reaction, and has poor filterability. There was a limit to its use on an experimental scale. In Swern oxidation, the reaction temperature must be kept at -60 ° C or lower for stabilizing the dimethyl sulfonium salt that is an oxidant, and a special reaction apparatus is required.
In addition, since dimethyl sulfide produced as a by-product has a bad odor, it has been a problem as a method for mass production. Further, the method using an oxoammonium salt has low industrial utility because the oxidant is expensive.

Therefore, an object of the present invention is to provide a method for producing aromatic or heterocyclic aldehydes industrially advantageously without the above problems, without requiring complicated operations and special conditions. It is in.

[0006]

In view of such circumstances, the present inventors have conducted diligent research, and as a result, using hexamethylenetetramine and a specific haloiminium salt for methanol substituted with an aromatic or heterocyclic ring. It was found that an aldehyde can be easily obtained under mild conditions by forming a hexaminium salt and hydrolyzing it with an acid, and completed the present invention. The production method of the present invention is shown by the following reaction formula.

[0007]

[Chemical 2]

(In the formula, R ¹ and R ² are the same or different and each is a lower alkyl group, X is a halogen atom,
n is 2 or 3, R ³ is an aromatic group or a heterocyclic group, and B is a base). That is, the present invention provides aromatic-substituted methanols or heterocyclic-substituted methanols (2) (hereinafter, “ Hexamethylenetetramine (3) and haloiminium salt (1) are used to form a hexaminium salt (5) in (methanols (2) ”), and the hexaminium salt (5) is hydrolyzed with an acid. The present invention provides a method for producing an aromatic or heterocyclic aldehyde (8) (hereinafter simply referred to as "aldehyde (8)").

Methanol, which is a raw material compound of the method of the present invention
R in the formula (2) in the class (2) ³With the group shown by
Is an optionally substituted aromatic group or heterocyclic group.
Is mentioned. In addition, the method of the present invention selectively
Only the hydroxyl group was oxidized and other functional groups were not affected.
Therefore, methanol (2) has ether bonds, double bonds, etc.
It does not matter even if it has a substituent containing.

In the present invention, the haloiminium salt used together with hexamethylenetetramine (3) is represented by the general formula (1), and R ¹ and R in the formula (1) are used.
Examples of the lower alkyl group represented by ² include a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group and an isobutyl group. Further, examples of the halogen atom represented by X include a fluorine atom, a chlorine atom, a bromine atom and an iodine atom, and among them, a chlorine atom is particularly preferable. In addition, preferable specific examples of the haloiminium salt (1) include 2-chloro-1,3-dimethylimidazolinium chloride and 2-chloro-1,3-dimethyl-3,4,5,6-tetrahydropyrimidinium. Examples thereof include chloride.

This haloiminium salt (1) is obtained by, for example, adding a compound represented by the above general formula (6), which is known as an easily available solvent, to oxalyl halogenide, phosphorus trihalide, phosphorus pentahalide, oxyhalogen. It can be easily obtained by reacting a halogenating agent known per se such as phosphorus oxide, phosgene, trichloromethyl chloroformate and the like. In this reaction, either compound (6) or a halogenating agent is dissolved in a suitable solvent such as carbon tetrachloride,
The other is added little by little to this, and the reaction is further carried out at room temperature to 70 ° C. for several hours to several tens of hours. The haloiminium salt (1) thus obtained can be isolated, but the reaction solution can also be used for the reaction of the present invention without isolation.

To carry out the method of the present invention, about 1 mol each of hexamethylenetetramine (3), haloiminium salt (1) and base (4) is added to 1 mol of methanol (2), and the mixture is heated at room temperature or under heating. You can react with. As the base used here, pyridine, triethylamine,
Tributylamine or the like can be used. The reaction solvent does not have to be used, but a solvent that does not participate in the reaction, such as a halogenated hydrocarbon such as dichloromethane or chloroform, a hydrocarbon, an ether, an aromatic hydrocarbon, or the like can be used.

The hexaminium salt (5) thus obtained can be easily converted to the aldehyde (8) by hydrolysis with an acid. For example, if the hexaminium salt (5) is dissolved in an acetic acid aqueous solution and reacted at room temperature or under heating for several hours, the aldehydes (8) can be easily obtained.
Can be obtained.

From the reaction mixture thus obtained,
To isolate and purify the desired aldehydes (8),
Distillation, recrystallization, etc. may be carried out by a conventional method.

The method of the present invention has the advantage that no environmental problems are caused because no heavy metal is used in the oxidation reaction, and since the haloiminium salt (1) is converted into the water-soluble compound (6), it can be easily separated and purified. is there. Therefore, isolation of the desired aldehyde from the reaction mixture can be conveniently carried out by a conventional method such as distillation or recrystallization.

[0016]

EFFECTS OF THE INVENTION According to the method of the present invention, aldehydes can be easily produced industrially advantageously under mild conditions.

[0017]

The present invention will be described in more detail with reference to examples, but the present invention is not limited thereto.

Example 1 Preparation of 4-methylbenzaldehyde: chloroform 10
5.0 g of 4-methylbenzyl alcohol in 0 ml (41
mmol) and 8.3 g (49 mmol) of 2-chloro-1,3-dimethylimidazolinium chloride, and 9.9 g (98 mmol) of triethylamine was added dropwise thereto. After completion of dropping, the mixture was stirred at room temperature for 2 hours, 8.0 g (57 mmol) of hexamethylenetetramine was added, and the mixture was heated under reflux for 12.5 hours. After cooling, the solvent was distilled off under reduced pressure, hexamethylenetetramine (3.0 g, 21 mmol) and 50% aqueous acetic acid solution (200 ml) were added to the obtained residue, and the mixture was heated under reflux for 6.5 hours. After allowing to cool, water was added to the reaction solution and the mixture was extracted with chloroform. The extract was washed successively with water, a saturated aqueous solution of sodium hydrogen carbonate and water, and dried over anhydrous magnesium sulfate. Then, the solvent was distilled off under reduced pressure to obtain a pale yellow oily substance, which was subjected to silica gel chromatography (solvent n-hexane / ethyl acetate).
The title compound was purified to obtain 3.1 g (yield 63%). IR ν _max ^neat cm ^-1 : 1700

Example 2 Preparation of 4-chlorobenzaldehyde: chloroform 10
5.0 g (35 g of 4-chlorobenzyl alcohol in 0 ml)
mmol) and 7.1 g (42 mmol) of 2-chloro-1,3-dimethylimidazolinium chloride, into which 8.5 g (84 mmol) of triethylamine was added dropwise. After completion of dropping, the mixture was stirred overnight at room temperature, 6.9 g (49 mmol) of hexamethylenetetramine was added, and the mixture was heated under reflux for 8.5 hours. After allowing to cool, the solvent was distilled off under reduced pressure, 3.1 g (22 mmol) of hexamethylenetetramine and 200 ml of 50% acetic acid aqueous solution were added to the residue, and the mixture was heated under reflux for 2.5 hours. After cooling, the same treatment as in Example 1 was carried out to obtain 3.1 g (yield 63%) of the title compound. IR ν _max ^KBr cm ^-1 : 1690

Example 3 Preparation of 4-methoxybenzaldehyde: chloroform 1
5.0 g of 4-methoxybenzyl alcohol in 00 ml
(36 mmol) and 7.3 g (43 mmol) of 2-chloro-1,3-dimethylimidazolinium chloride were added, and 8.8 g (87 mmol) of triethylamine was added dropwise thereto. After completion of dropping, the mixture was stirred at room temperature for 1 hour, 7.1 g (51 mmol) of hexamethylenetetramine was added, and the mixture was heated under reflux for 6.5 hours. After allowing to cool, the solvent was distilled off under reduced pressure, 200 ml of a 50% acetic acid aqueous solution was added to the obtained residue, and the mixture was heated under reflux for 2.5 hours. After cooling, the same treatment as in Example 1 was carried out to obtain 2.9 g (yield 59%) of the title compound. IR ν _max ^neat cm ^-1 : 1685

Example 4 Preparation of 2-thiophene aldehyde: Chloroform 100
5.0 g (44 mmol) of 2-thiophene methanol in ml
And 2-chloro-1,3-dimethylimidazolinium chloride (8.9 g, 53 mmol) were added, and triethylamine (10.6 g, 105 mmol) was added dropwise thereto. After completion of dropping, the mixture was stirred at room temperature for 1 hour, 8.6 g (61 mmol) of hexamethylenetetramine was added, and the mixture was heated under reflux for 14.5 hours. After cooling, the solvent was distilled off under reduced pressure, and 3.1 g (22 mmol) of hexamethylenetetramine and 200 ml of 50% acetic acid aqueous solution were added to the resulting residue, and the mixture was heated under reflux for 3 hours. After cooling, the same treatment as in Example 1 was carried out to obtain 2.7 g (yield 55%) of the title compound. IR ν _max ^neat cm ^-1 : 1675

─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. ⁵ Identification code Internal reference number FI Technical indication C07C 47/575 7457-4H C07D 333/22

Claims (1)

[Claims] 1. Aromatic-substituted or heterocyclic-substituted methanol containing hexamethylenetetramine and the following general formula (1): [Wherein R ¹ and R ² are the same or different and each represents a lower alkyl group, X represents a halogen atom, and n represents 2 or 3] to form a hexaminium salt, A method for producing an aromatic or heterocyclic aldehyde, which comprises hydrolyzing the hexaminium salt with an acid.