JP4706325B2 - Method for obtaining 4-substituted-1-N, N-dialkylamino-1-buten-3-one - Google Patents

Description

  The present invention relates to a mixture of 4-substituted-1-N, N-dialkylamino-1-buten-3-one and 2-substituted-1-N, N-dialkylamino-1-buten-3-one, It relates to a method for obtaining 4-substituted-1-N, N-dialkylamino-1-buten-3-one. 4-Substituted-1-N, N-dialkylamino-1-buten-3-one is a useful compound as a synthetic intermediate for raw materials and photographic chemicals, for example, as a synthetic intermediate for pharmaceuticals and agricultural chemicals.

Conventionally, a method for producing 4-substituted-1-N, N-dialkylamino-1-buten-3-one is already known (for example, see Non-Patent Document 1). However, at the same time as the formation of 4-substituted-1-N, N-dialkylamino-1-buten-3-one, the boiling point is very close, which makes it difficult to separate and purify by distillation. There was a problem that a large amount of N-dialkylamino-1-buten-3-one (positional isomer) was by-produced. Therefore, a method for selectively obtaining only 4-substituted-1-N, N-dialkylamino-1-buten-3-one has been desired.
Chem. Ber., 97, 3392 (1964)

  The object of the present invention is to solve the above-mentioned problems and to give 4-substituted-1-N, N-dialkylamino-1-buten-3-one and 2-substituted-1-N, N by a simple method. Can selectively obtain 4-substituted-1-N, N-dialkylamino-1-buten-3-one from a mixture with 2-dialkylamino-1-buten-3-one (regioisomer mixture) It is an object of the present invention to provide a method for obtaining a particularly suitable 4-substituted-1-N, N-dialkylamino-1-buten-3-one.

  The subject of this invention is general formula (1) which is a regioisomer with respect to each other.

(In the formula, R ¹ represents a hydrocarbon group which may have a substituent, and R ² and R ³ represent an alkyl group.)
4-substituted-1-N, N-dialkylamino-1-buten-3-one represented by the general formula (2)

(In the formula, R ¹ , R ² and R ³ are as defined above.)
4-substituted-1-N, N-dialkylamino-1-buten-3-one was obtained from a mixture with 2-substituted-1-N, N-dialkylamino-1-buten-3-one represented by A mixture of 4-substituted-1-N, N-dialkylamino-1-buten-3-one and 2-substituted-1-N, N-dialkylamino-1-buten-3-one Is reacted with an acid to selectively decompose only 2-substituted-1-N, N-dialkylamino-1-buten-3-one, and 4-substituted-1-N, N-dialkylamino-1- It is solved by a process for obtaining 4-substituted-1-N, N-dialkylamino-1-buten-3-one, characterized in that it provides buten-3-one.

  According to the present invention, 4-substituted-1-N, N-dialkylamino-1-buten-3-one and 2-substituted-1-N, N-dialkylamino-1-buten-3-one can be synthesized by a simple method. 4-substituted-1-N, N-dialkylamino-1-buten-3-one can be obtained selectively from a mixture of the above (positional isomer mixture) Thus, a method for obtaining N-dialkylamino-1-buten-3-one can be provided.

The 4-substituted-1-N, N-dialkylamino-1-buten-3-one and 2-substituted-1-N, N-dialkylamino-1-buten-3-one used in the reaction of the present invention are: It is represented by the general formulas (1) and (2). In the general formulas (1) and (2), R ¹ is a hydrocarbon group which may have a substituent. Specifically, for example, a methyl group, an ethyl group, a propyl group, a butyl group, Alkyl groups such as pentyl group, hexyl group, heptyl group, octyl group, nonyl group, decyl group, undecyl group, dodecyl group; cycloalkyl groups such as cyclopropyl group, cyclobutyl group, cyclopentyl group, cyclohexyl group, cycloheptyl group; Examples include aralkyl groups such as benzyl group, phenethyl group, and phenylpropyl group; and aryl groups such as phenyl group, naphthyl group, and anthryl group. These groups include various isomers.

  The hydrocarbon group may have a substituent. Examples of the substituent include a substituent formed through a carbon atom, a substituent formed through an oxygen atom, a substituent formed through a nitrogen atom, a substituent formed through a sulfur atom, and a halogen atom.

  Examples of the substituent formed through the carbon atom include alkyl groups such as a methyl group, an ethyl group, a propyl group, a butyl group, a pentyl group, and a hexyl group; a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, a cyclohexyl group, and a cyclo group. Cycloalkyl groups such as heptyl group; Alkenyl groups such as vinyl group, allyl group, propenyl group, cyclopropenyl group, cyclobutenyl group, cyclopentenyl group; quinolyl group, pyridyl group, pyrrolidyl group, pyrrolyl group, furyl group, thienyl group, etc. An aryl group such as phenyl group, tolyl group, fluorophenyl group, xylyl group, biphenylyl group, naphthyl group, anthryl group, phenanthryl group; acetyl group, propionyl group, acryloyl group, pivaloyl group, cyclohexylcarbonyl group, Benzoyl group, naphthoyl Group, acyl group such as toluoyl group (may be acetalized); carboxyl group; alkoxycarbonyl group such as methoxycarbonyl group and ethoxycarbonyl group; aryloxycarbonyl group such as phenoxycarbonyl group; trifluoromethyl group and the like A halogenated alkyl group; and a cyano group. These groups include various isomers.

  Examples of the substituent formed through the oxygen atom include a hydroxyl group; an alkoxyl group such as a methoxyl group, an ethoxyl group, a propoxyl group, a butoxyl group, a pentyloxyl group, a hexyloxyl group, a heptyloxyl group, and a benzyloxyl group; Aryloxyl groups such as phenoxyl group, toluyloxyl group, naphthyloxyl group and the like can be mentioned. These groups include various isomers.

  Examples of the substituent formed through the nitrogen atom include a primary amino group such as a methylamino group, an ethylamino group, a propylamino group, a butylamino group, a cyclohexylamino group, a phenylamino group, and a naphthylamino group; Secondary amino groups such as amino group, diethylamino group, dipropylamino group, dibutylamino group, methylethylamino group, methylpropylamino group, methylbutylamino group, diphenylamino group, N-methyl-N-methanesulfonylamino group A morpholino group, a piperidino group, a piperazinyl group, a pyrazolidinyl group, a pyrrolidino group, an indolyl group or the like; an imino group; These groups include various isomers.

  Examples of the substituent formed through the sulfur atom include a mercapto group; a thioalkoxyl group such as a thiomethoxyl group, a thioethoxyl group, and a thiopropoxyl group; a thiophenoxyl group, a thiotoluyloxyl group, and a thionaphthyloxyl group. Thioaryloxyl group and the like. These groups include various isomers.

  Examples of the halogen atom include a fluorine atom, a chlorine atom, a bromine atom, and an iodine atom.

R ² and R ³ are alkyl groups, which are synonymous with those defined for R ¹ . R ² and R ³ may be bonded to each other to form a ring.

  4-Substituted-1-N, N-dialkylamino-1-buten-3-one and 2-substituted-1-N, N-dialkylamino-1-buten-3-one used in the reaction of the present invention The mixture (positional isomer mixture) is, for example, reaction process formula (1)

(In the formula, R ¹ , R ² and R ³ are as defined above, and R ⁴ represents an alkyl group.)
As shown in the above, it is obtained by reacting a ketone compound with N, N-dialkylformamide dialkyl acetal (described in Reference Examples 1 and 2 below).

Examples of the acid used in the present invention include inorganic acids such as hydrochloric acid, sulfuric acid and phosphoric acid; and organic acids such as formic acid, acetic acid and oxalic acid. Preferably, hydrochloric acid and sulfuric acid are used. In addition,
These acids may be used alone or in combination of two or more.

  The amount of the acid used is preferably 0.1 to 10 mol, more preferably 1 to 5 mol, per 1 mol of 2-substituted-1-N, N-dialkylamino-1-buten-3-one in the mixture. It is.

  The decomposition reaction of the present invention is preferably carried out in the presence of water, and the amount of water used is 1 g of 2-substituted-1-N, N-dialkylamino-1-buten-3-one in the mixture. On the other hand, it is preferably 0.1-30 g, more preferably 0.5-10 g.

  The decomposition reaction of the present invention may be carried out in the presence of an organic solvent, and the solvent used is not particularly limited as long as it does not inhibit the reaction. For example, nitriles such as acetonitrile, propionitrile, benzonitrile, etc. Aliphatic hydrocarbons such as hexane, heptane, octane, nonane, decane, undecane and dodecane; aromatic hydrocarbons such as toluene, xylene, mesitylene and cumene; halogenated aliphatic hydrocarbons such as methylene chloride and dichloroethane Halogenated aromatic hydrocarbons such as chlorobenzene; ethers such as diethyl ether, diisopropyl ether, tetrahydrofuran and the like, and aromatic hydrocarbons are preferably used. In addition, you may use these organic solvents individually or in mixture of 2 or more types.

  The amount of the organic solvent to be used is preferably 1-30 g, more preferably 2-10 g, per 1 g of 4-substituted-1-N, N-dialkylamino-1-buten-3-one.

  The reaction of the present invention includes, for example, 4-substituted-1-N, N-dialkylamino-1-buten-3-one and 2-substituted-1-N, N-dialkylamino-1-buten-3-one The mixture and the acid are mixed and stirred. The reaction temperature at that time is preferably -20 to 100 ° C, more preferably 0 to 50 ° C, and the reaction pressure is not particularly limited.

  After completion of the decomposition reaction of the present invention, a base is added to the reaction solution to remove decomposition products (for example, 2-substituted-1-hydroxy-1-buten-3-one, dialkylamine, etc.) into the aqueous layer, and 4-substituted A method for obtaining an organic layer containing -1-N, N-dialkylamino-1-buten-3-one is preferably carried out. Isolation of 4-substituted-1-N, N-dialkylamino-1-buten-3-ones from organic layers containing 4-substituted-1-N, N-dialkylamino-1-buten-3-ones For purification, an organic layer containing 4-substituted-1-N, N-dialkylamino-1-buten-3-one is generally used for washing, filtration, concentration, distillation, recrystallization, column chromatography, etc. It can be done by a typical method.

  Examples of the base used in the post-treatment of the present invention include alkali metal hydroxides such as sodium hydroxide and potassium hydroxide; alkaline earth metal hydroxides such as magnesium hydroxide and calcium hydroxide; sodium carbonate and carbonate Antarctic metal carbonates such as potassium; alkaline earth metal carbonates such as magnesium carbonate and calcium carbonate; alkali metal hydrogen carbonates such as sodium hydrogen carbonate and potassium hydrogen carbonate; alkaline earth metals such as magnesium hydrogen carbonate and calcium hydrogen carbonate Examples of the hydrogen carbonate include alkali metal hydroxides and alkaline earth metal hydroxides, and more preferably sodium hydroxide, potassium hydroxide, and magnesium hydroxide. In addition, you may use these bases individually or in mixture of 2 or more types.

  The amount of the base used is preferably 0.1 to 5 mol, more preferably 0.5 to 3 mol, per 1 mol of the acid used.

  Next, the present invention will be specifically described with reference to examples, but the scope of the present invention is not limited thereto.

Reference Example 1 ([R ¹ = R ² = R ³ = R ⁴ = methyl group]; 1-N, N-dimethylamino-1-penten-3-one and 1-N, N-dimethylamino-2-methyl Synthesis of a mixture of 1-buten-3-one)
A glass reactor having an internal volume of 1000 ml equipped with a stirrer, a thermometer and a reflux condenser was charged with 72.11 g (1.0 mol) of 2-butanone, 59.58 g (0.5 mol) of N, N-dimethylformamide dimethylacetal and N, N. -361 ml of dimethylformamide was added and reacted at 110-120 ° C for 10 hours with stirring. After completion of the reaction, the reaction solution was analyzed by gas chromatography. As a result, 1-N, N-dimethylamino-1-penten-3-one and 1-N, N-dimethylamino-2-methyl-1-butene-3 The production ratio (mole) of -one was 61:39.
Subsequently, the reaction solution was distilled under reduced pressure (95 ° C., 0.4 kPa), and 19.78 g of 1-N, N-dimethylamino-1-penten-3-one and 1-N, N-dimethylamino-2-methyl-1- 33.16 g of a mixture containing 12.72 g of buten-3-one was obtained.

Example 1 (Acquisition of 1-N, N-dimethylamino-1-penten-3-one)
After adding 33.16 g of the mixture obtained in Reference Example 1, 50 ml of toluene and 25 ml of water to a 200 ml flask equipped with a stirrer, thermometer and dropping funnel, slowly add 10 ml (0.12 mol) of concentrated hydrochloric acid. And allowed to react at room temperature for 1 hour.
After completion of the reaction, 27.5 ml (0.22 mol) of 8 mol / l sodium hydroxide aqueous solution was slowly added to the reaction solution, and the mixture was stirred at room temperature for 1 hour. The organic layer was separated and analyzed by gas chromatography. 16.8 g of 1-N, N-dimethylamino-1-penten-3-one, 1-N, N-dimethylamino-2-methyl-1-butene There was 0.64 g of -3-one. The abundance ratio of 1-N, N-dimethylamino-1-penten-3-one and 1-N, N-dimethylamino-2-methyl-1-buten-3-one was 96: 4 there were.

Reference Example 2 ([R ¹ = n-propyl group, R ² = R ³ = R ⁴ = methyl group]; 1-N, N-dimethylamino-1-hepten-3-one and 1-N, N-dimethyl Synthesis of a mixture of amino-2-n-propyl-1-buten-3-one)
To a glass reactor having an internal volume of 1000 ml equipped with a stirrer, a thermometer and a reflux condenser, 2-hexanone 100.16 g (1.0 mol), N, N-dimethylformamide dimethyl acetal 59.58 g (0.5 mol) and N, N -361 ml of dimethylformamide was added and reacted at 110-120 ° C for 10 hours with stirring. After completion of the reaction, the reaction solution was analyzed by gas chromatography. As a result, 1-N, N-dimethylamino-1-hepten-3-one and 1-N, N-dimethylamino-2-n-propyl-1-butene were analyzed. The production ratio (mole) of -3-one was 83:17.
Next, the reaction solution was distilled under reduced pressure (113 ° C., 0.4 kPa), and 37.89 g of 1-N, N-dimethylamino-1-hepten-3-one and 1-N, N-dimethylamino-2-n-propyl- 46.58 g of a mixture containing 7.76 g of 1-buten-3-one was obtained.

Example 2 (Acquisition of 1-N, N-dimethylamino-1-hepten-3-one)
After adding 46.58 g of the mixture obtained in Reference Example 2, 60 ml of toluene and 30 ml of water to a 200-ml flask equipped with a stirrer, thermometer and dropping funnel, 5 ml (0.06 mol) of concentrated hydrochloric acid was slowly added. And allowed to react at room temperature for 1 hour.
After completion of the reaction, 13.7 ml (0.11 mol) of 8 mol / l sodium hydroxide aqueous solution was slowly added to the reaction solution, and the mixture was stirred at room temperature for 1 hour. The organic layer was separated and analyzed by gas chromatography, 1-N, N-dimethylamino-1-hepten-3-one 33.0 g, 1-N, N-dimethylamino-2-n-propyl-1 -0.47 g of buten-3-one was present. The abundance ratio (mol) of 1-N, N-dimethylamino-1-hepten-3-one and 1-N, N-dimethylamino-2-n-propyl-1-buten-3-one was 99: It was 1.

  The present invention relates to a mixture of 4-substituted-1-N, N-dialkylamino-1-buten-3-one and 2-substituted-1-N, N-dialkylamino-1-buten-3-one, It relates to a process for obtaining 4-substituted-1-N, N-dialkylamino-1-buten-3-one. 4-Substituted-1-N, N-dialkylamino-1-buten-3-one is a useful compound as a synthetic intermediate for raw materials and photographic chemicals, for example, as a synthetic intermediate for pharmaceuticals and agricultural chemicals.

Claims (3)

General formula (1) which is a positional isomer to each other

(In the formula, R ¹ represents a hydrocarbon group which may have a substituent, and R ² and R ³ represent an alkyl group.)
4-substituted-1-N, N-dialkylamino-1-buten-3-one represented by the general formula (2)

(In the formula, R ¹ , R ² and R ³ are as defined above.)
4-substituted-1-N, N-dialkylamino-1-buten-3-one was obtained from a mixture with 2-substituted-1-N, N-dialkylamino-1-buten-3-one represented by A mixture of 4-substituted-1-N, N-dialkylamino-1-buten-3-one and 2-substituted-1-N, N-dialkylamino-1-buten-3-one Is reacted with an acid to selectively decompose only 2-substituted-1-N, N-dialkylamino-1-buten-3-one, and 4-substituted-1-N, N-dialkylamino-1 A method for obtaining 4-substituted-1-N, N-dialkylamino-1-buten-3-one, characterized in that -buten-3-one is obtained.   The 4-substituted-1-N, N-dialkylamino-1- according to claim 1, wherein the decomposition reaction of 2-substituted-1-N, N-dialkylamino-1-buten-3-one is carried out in the presence of water. How to get buten-3-one.   After reacting the mixture with an acid to decompose 2-substituted-1-N, N-dialkylamino-1-buten-3-one, a base was added to the reaction solution to remove the decomposition product into the aqueous layer, The 4-substituted-1-N, N-dialkylamino-1-butene-3 according to claim 1, wherein an organic layer containing 4-substituted-1-N, N-dialkylamino-1-buten-3-one is obtained. -How to get on.