JP4706320B2 - Method for producing N, N-dimethylaminoalkenone compound - Google Patents

Description

  The present invention relates to a method for producing an N, N-dimethylaminoalkenone compound. N, N-dimethylaminoalkenone compounds are useful compounds as synthetic intermediates and raw materials for pharmaceuticals and agricultural chemicals, and synthetic raw materials for photographic chemicals.

Conventionally, as a method for producing an N, N-dimethylaminoalkenone compound, for example, 4,4-dimethoxy-2-butanone and dimethylamine are reacted overnight in methanol at room temperature, yield 85.7 A method for producing 4- (N, N-dimethylamino) -3-buten-2-one in% is disclosed (for example, see Non-Patent Document 1). However, in this method, dimethylamine or its methanol solution, which is difficult to handle industrially, is used, and the substrate concentration is low, so that the reaction rate is slow and the yield of the target product is low. In addition, 4,4-dimethoxy-2-butanone and dimethylamine tetrahydrofuran were reacted at 5 ° C. for 1 hour to give 4- (N, N-dimethylamino) -3-butene-2-yl at a yield of 95%. A method for producing ON is disclosed (for example, see Non-Patent Document 2). However, this method has a problem that a tetrahydrofuran solution of dimethylamine, which is difficult to handle industrially, is used, and the reaction must be performed at a low temperature. In any of the above cases, there were various problems, and the industrial production method was not satisfactory.
Org.Prep.Proc.Int., 16 (1), 31 (1984) J. Org. Chem., 64, 3047 (1999)

  The object of the present invention is to solve the above-mentioned problems, and can produce an N, N-dimethylaminoalkenone compound in a high yield under a mild condition by a simple method. The object is to provide a process for producing a dimethylaminoalkenone compound.

  The subject of this invention is general formula (1).

(In the formula, R ¹ represents a hydrocarbon group which may have a substituent, and R ² represents a hydrocarbon group. R ² are bonded to each other to form a ring. Is also good.)
A ketoacetal compound represented by the formula (2) is reacted with a dimethylamine aqueous solution.

(Wherein R ¹ has the same meaning as described above.)
It can be solved by the production method of N, N-dimethylaminoalkenone compound represented by

  According to the present invention, an industrially suitable method for producing an N, N-dimethylaminoalkenone compound, which can produce an N, N-dimethylaminoalkenone compound in a high yield by a simple method, can be provided.

The ketoacetal compound used in the reaction of the present invention is represented by the general formula (1). In the general formula (1), R ¹ is a hydrocarbon group which may have a substituent. Specifically, for example, methyl group, ethyl group, propyl group, butyl group, pentyl group, hexyl Group, heptyl group, octyl group, nonyl group, decyl group, undecyl group, dodecyl group and other alkyl groups; cyclopropyl group, cyclobutyl group, cyclopentyl group, cyclohexyl group, cycloheptyl group and other cycloalkyl groups; benzyl group, phenethyl Group, an aralkyl group such as a phenylpropyl group; and an aryl group such as a phenyl group, a naphthyl group, and an 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 methyl group, ethyl group, propyl group, butyl group, pentyl group, and hexyl group; cyclopropyl group, cyclobutyl group, cyclopentyl group, cyclohexyl group, and cyclobutyl. Cycloalkyl groups such as groups; alkenyl groups such as vinyl groups, allyl groups, propenyl groups, cyclopropenyl groups, cyclobutenyl groups, cyclopentenyl groups; quinolyl groups, pyridyl groups, pyrrolidyl groups, pyrrolyl groups, furyl groups, thienyl groups, etc. Heterocyclic group: 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 Naphthoyl An 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; halogen such as trifluoromethyl group An alkyl group; 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 butylamino group, a cyclohexylamino group, a phenylamino group, or a naphthylamino group; a dimethylamino group, diethylamino Groups, dibutylamino groups, methylethylamino groups, methylbutylamino groups, diphenylamino groups, secondary amino groups such as N-methyl-N-methanesulfonylamino groups; morpholino groups, piperidino groups, piperazinyl groups, pyrazolidinyl groups, pyrrolidino A heterocyclic amino group such as a group or an indolyl group; 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 is a hydrocarbon group, which has the same meaning as defined for R ¹ . R ² may be bonded to each other to form a ring.

  The concentration of the aqueous dimethylamine solution used in the reaction of the present invention is preferably 10 to 80% by mass, more preferably 20 to 60% by mass.

  The amount of the dimethylamine used is preferably 0.5 to 10 mol, more preferably 0.8 to 5 mol in terms of dimethylamine, with respect to 1 mol of the ketoacetal compound.

  The reaction of the present invention is performed, for example, by a method of mixing a ketoacetal compound and a dimethylamine compound and stirring the mixture. The reaction temperature at that time is preferably 0 to 80 ° C., more preferably 10 to 50 ° C., and the reaction pressure is not particularly limited.

  The N, N-dimethylaminoalkenone compound obtained by the reaction of the present invention is isolated and purified by a general method such as extraction, filtration, concentration, distillation, recrystallization, column chromatography, etc. after completion of the reaction. .

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

Example 1 (Synthesis of 4- (N, N-dimethylamino) -3-buten-2-one)
To a 300 ml flask equipped with a stirrer, thermometer and reflux condenser, 142.7 g (1.08 mol) of 4,4-dimethoxy-2-butanone and 106.7 g (1.18 mmol) of 50% by weight dimethylamine aqueous solution were added, The reaction was carried out at 25 ° C. for 4 hours with stirring. After completion of the reaction, the reaction solution was concentrated, and the concentrate was distilled under reduced pressure (115 to 120 ° C., 900 Pa) to give 117.1 g of 4- (N, N-dimethylamino) -3-buten-2-one as a pale yellow liquid. (Isolation yield; 95%).
The physical properties of 4- (N, N-dimethylamino) -3-buten-2-one were as follows.

¹ H-NMR (CDCl ₃ , δ (ppm)); 2.10 (3H, s), 2.94 (6H, brs), 5.05 (1H, d, J = 12.7 Hz), 7.47 (1H, d, J = 12.7 Hz) )

Example 2 (Synthesis of 4- (N, N-dimethylamino) -3-buten-2-one)
To a flask with an internal volume of 100 ml equipped with a stirrer, a thermometer and a reflux condenser, 3,9.7 g (0.30 mol) of 4,4-dimethoxy-2-butanone and 29.8 g (0.33 mmol) of a 50 mass% aqueous dimethylamine solution were added, The reaction was carried out at 25 ° C. for 4 hours with stirring. After completion of the reaction, the reaction solution was concentrated under reduced pressure. Next, 60 ml of toluene was added to the concentrate obtained, and the mixture was again concentrated under reduced pressure, and 4- (N, N-dimethylamino)-with a purity of 95.1% (quantitative value by high performance liquid chromatography) was obtained as a pale yellow liquid. 34.7 g of 3-buten-2-one was obtained (isolation yield; 97%).

  The present invention relates to a method for producing an N, N-dimethylaminoalkenone compound. N, N-dimethylaminoalkenone compounds are useful compounds as synthetic intermediates and raw materials for pharmaceuticals and agricultural chemicals, and synthetic raw materials for photographic chemicals.

Claims (2)

General formula (1)

(In the formula, R ¹ represents a hydrocarbon group which may have a substituent, and R ² represents a hydrocarbon group.)
A ketoacetal compound represented by the formula (2) is reacted with a dimethylamine aqueous solution.

(Wherein R ¹ has the same meaning as described above.)
The manufacturing method of the N, N- dimethylamino alkenone compound shown by these.   The process for producing an N, N-dimethylaminoalkenone compound according to claim 1, wherein the concentration of the aqueous dimethylamine solution is 10 to 80% by mass.