JP2000053592A - Acylation - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide an acylation method capable of being carried out without using an organic solvent. SOLUTION: This acylation method comprises acylating the amino group of an amine compound of general formula I: Ar-NH2 (Ar is an aryl group or an aromatic heterocyclic group) with an acylating agent of general formula II: R-COX (R is an alkyl group, a cycloalkyl group or an alkenyl group; X is a releasing group) in supercritical or semicritical carbon dioxide as a reaction medium.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a method for acylating an amino group of an amine compound using an acylating agent, and more particularly, to a method for acylating an amine compound using an acylating agent without using an organic solvent. The present invention relates to a method for acylating an amino group.

[0002]

BACKGROUND OF THE INVENTION Acylated amines are important substances as compounds for use in photographic and other applications and as intermediates for synthesizing these compounds.

Conventionally, acylated amines have been synthesized by using nitriles (eg, acetonitrile), ethers (eg, diethyl ether, dioxane, tetrahydrofuran), and hydrocarbons (eg, toluene, toluene) in addition to dimethylformamide.
Organic solvents such as xylene) have been used. However, the use of such an organic solvent can efficiently synthesize the compound, but the use of an expensive organic solvent increases the cost, and the organic solvent becomes difficult to dispose of from the viewpoint of environmental problems. As a result, the cost for collection and disposal was high, and there was a problem.

When a substance in a liquid or gaseous state is heated to a high temperature and a high pressure, the densities of the gas phase and the liquid phase become equal, and the liquid and the gas cannot be distinguished from each other. This is a supercritical fluid, which, in addition to its ability to dissolve substances like a liquid, has high permeability and fluidity by entering anywhere like a gas.

Techniques for performing various reactions using these supercritical fluids have been developed. As these techniques, there is a technique of detoxifying harmful substances using supercritical water. When the temperature of the water is 374.1 ° C. and 22.12 MPa or more, the water becomes supercritical water, and the contaminated soil and incinerated ash are decomposed into harmless carbon dioxide (CO ₂ ), hydrochloric acid, inorganic salts, and the like.

[0006] Decomposition of organic chlorine compounds such as dioxin and specific chlorofluorocarbon has also been performed.

[0007] The use of supercritical carbon dioxide in the synthesis reaction has also been developed. For example, using supercritical carbon dioxide as a solvent, a cyclic alkylidene glycerol and a fatty acid are separated from a reaction column packed with immobilized lipase. Japanese Patent Application Laid-Open No. 7-67677 discloses that a cyclic alkylidene glycerol acyl ester is produced by using a separation and purification column packed with an agent to perform synthesis and removal of unreacted fatty acids,
Japanese Patent Application Laid-Open No. 9-283 discloses that the esterification reaction between a primary terpene alcohol and a fatty acid is continuously performed in a reactor filled with a powder on which a lipase enzyme is immobilized in a supercritical carbon dioxide atmosphere. Japanese Patent Application Laid-Open No. 9-59205 describes that an aromatic acyl compound is produced by reacting an aromatic compound with an acylating agent using a carbon dioxide in a state as a reaction medium and a Friedel-Crafts catalyst.

There are many examples of the application of supercritical fluids, such as the decomposition of organic substances by water and the extraction of active ingredients and harmful substances from natural products and mixtures by carbon dioxide. Is not much yet. By utilizing the special properties of supercritical fluids, i.e., large solubility, permeability, and special dissociation state in water, change in dielectric constant, etc., it can exhibit reactivity that cannot be obtained at normal temperature and pressure. Be expected.

Therefore, the present inventors have studied and found that the use of supercritical or subcritical carbon dioxide as a reaction medium enables the acylation of amines without using a conventionally used organic solvent. It has been found that conversion can be performed.

[0010]

Accordingly, an object of the present invention is to provide an acylation method which can be performed without using an organic solvent.

[0011]

The object of the present invention is to provide a supercritical or subcritical carbon dioxide as a reaction medium.
An acylation method comprising acylating an amino group of an amine compound represented by the following general formula [I] with an acylating agent represented by the following general formula [II]. General formula [I] Ar-NH ₂ [In the formula, Ar represents an aryl group or an aromatic heterocyclic group. General formula [II] R-COX [wherein, R represents an alkyl group, a cycloalkyl group or an alkenyl group, and X represents a leaving group. ].

Hereinafter, the present invention will be described in detail.

The acylation method of the present invention comprises acylating an amino group of an amine compound represented by the general formula [I] with an acylating agent represented by the general formula [II]. A compound represented by the following general formula [III] is synthesized. General formula [III] Ar-NHCO-R [wherein, Ar represents an aryl group or an aromatic heterocyclic group, and R represents an alkyl group, a cycloalkyl group, or an alkenyl group. The general formulas [I], [II] and [III] will be described.

As the aryl group represented by Ar, an aryl group having 6 to 14 carbon atoms (for example, a phenyl group,
1-naphthyl group, 9-anthranyl group, etc.).

These aryl groups may further have a substituent. The substituent is not particularly limited and may be various ones.Typical substituents include an alkyl group, an aryl group, an anilino group, an acylamino group, a sulfonamide group, an alkylthio group, an arylthio group, an alkenyl group, Examples of each group such as a cycloalkyl group, other than the above, a halogen atom and a cycloalkenyl group, an alkynyl group, a heterocyclic group, a sulfonyl group, a sulfinyl group, a phosphonyl group, an acyl group, a carbamoyl group, a sulfamoyl group, a cyano group, Alkoxy group, aryloxy group, heterocyclic oxy group, siloxy group, acyloxy group, sulfonyloxy group, carbamoyloxy group, alkylamino group,
Imide group, ureido group, sulfamoylamino group, alkoxycarbonylamino group, aryloxycarbonylamino group, alkoxycarbonyl group, aryloxycarbonyl group, heterocyclic thio group, thioureido group, carboxy group, nitro group, sulfo group, etc. And spiro compound residues, bridged hydrocarbon compound residues, and the like.

Examples of the aromatic heterocyclic group include a 2-pyridyl group, a 3-pyridyl group and a 2-benzothiazole group.

These aromatic heterocyclic groups may further have a substituent. The substituent is not particularly limited and may be various. Typical examples of the substituent include those described above as the substituent which the aryl group may have.

The alkyl group represented by R includes:
Examples include a methyl group, an ethyl group, an i-propyl group, an n-butyl group, an n-dodecyl group, an iso-hexadecyl group and the like, and examples of the cycloalkyl group include a cyclopropyl group and a cyclohexyl group. Examples of the alkenyl group include a vinyl group, an allyl group, and a 2-dodecenyl group.

These alkyl, cycloalkyl and alkenyl groups may further have a substituent. The substituent is not particularly limited and may be various. Typical examples of the substituent include those described above as the substituent which the aryl group may have.

Examples of the leaving group represented by X include a halogen atom, a hydroxyl group, a carbonyloxy group (eg, an acetyloxy group), a sulfonyloxy group (eg, a methylsulfonyloxy group, a p-toluenesulfonyloxy group). Group), an alkoxy group (eg, a methoxy group, an ethoxy group, etc.), an aryloxy group (eg, a phenoxy group, etc.), and the like.

Hereinafter, specific examples of the amine compound represented by the general formula [I], specific examples of the acylating agent represented by the general formula [II], and the general formula obtained by the acylation method of the present invention will be described. Specific examples of the compound represented by [III] are shown, but the description of the specific examples does not limit the present invention.

[0022]

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[0023]

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[0024]

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[0025]

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[0026]

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[0027]

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[0028]

Embedded image In the acylation of the amino group of the amine compound represented by the general formula [I], the acylating agent represented by the general formula [II] includes:
0.1 mol per mol of the amine compound represented by the general formula [I].
It is preferably used in the range of 7 to 2 mol, and
It is particularly preferred to be in the range of 1.5 mol.

Next, supercritical or subcritical carbon dioxide used as a reaction medium in the acylation method of the present invention will be described.

Every fluid (liquid, gas) has a critical temperature (Tc) and a critical pressure (Pc). Normally, if a gas is compressed, a liquid phase appears with an increase in the density, and the gas and liquid coexist. Conversely, if the temperature of the liquid is increased, the density is reduced by molecular motion, and at the same time, the gas is vaporized to generate a gas phase.
As the pressure and temperature are increased, the density of the gas and liquid finally agrees, making it difficult to distinguish between gas and liquid phases.
It reaches a gas-liquid critical point (also simply referred to as "critical point"). The pressure at this time is called a critical pressure, and the temperature is called a critical temperature, which is a value specific to the substance. The density under the critical temperature (Tc) and the critical pressure (Pc) is called critical density (Dc). In the present invention, carbon dioxide or water in a supercritical state refers to carbon dioxide that is at or above this critical pressure (Pc) and critical temperature (Tc).

The critical temperature (Tc), critical pressure (Pc) and critical density (Dc) of carbon dioxide are as follows: Tc = 31.1 ° C.
c = 7.38 MPa, Dc = 0.466 g / cm ³ . The supercritical carbon dioxide means carbon dioxide at a temperature of 31.1 ° C. or more and a pressure of 7.38 MPa or more. The term "subcritical carbon dioxide" as used herein refers to a state within a range of up to 0.6 times the critical temperature (Tc) and critical pressure (Pc). It is defined as being in the pressure range.

Critical temperature (Tc)> Subcritical temperature ≧ 0.6 ×
Critical temperature (Tc) Critical pressure (Pc)> subcritical pressure ≧ 0.6 × critical pressure (P
c) The reaction temperature is preferably higher than the temperature defined herein,
If the pressure is too high, there is a limit to the cost of the apparatus accompanying the increase in pressure and the occurrence of side reactions and thermal decomposition reactions. The limits vary greatly depending on the type of chemical reaction selected and cannot be said uniformly.

The reaction time varies depending on the type and amount of the compounds represented by the general formulas [I] and [II], the reaction temperature and the reaction conditions, but is usually between several minutes and 24 hours.

The compound produced by the reaction can be used as it is in the next reaction, and after completion of the reaction, it can be easily separated and purified by a conventional method, for example, by recrystallization to obtain the compound.

[0035]

EXAMPLES Hereinafter, the present invention will be described specifically with reference to examples, but the present invention is not limited to these examples.

EXAMPLES 1-4 A batch type autoclave (SUS-316) having a capacity of 10 mL was used.
Was filled with 2-methoxy-5-nitroaniline (MNA), tert-butylcarbonylacetic acid methyl ester (tBu-deriv), and dry ice in the amounts described in Table 1 and sealed. Heated at the temperature described in Table 1 for 1 hour. Next, the autoclave was put into a water bath, rapidly cooled to room temperature to stop the reaction, the autoclave was gradually opened, and the carbon dioxide sealed under pressure was released. The solid substance and viscous substance remaining in the autoclave were dissolved in ethyl acetate, and then the acylated product as a target product was quantified by liquid chromatography according to a conventional method, and 2-methoxy-5-nitroaniline (MN
The yield based on A) was determined. Table 1 shows the obtained results.

[0037]

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[0038]

[Table 1]

According to the results shown in Table 1, the target acylated product was obtained at a yield of about 30%, regardless of the amount of the charged autoclave. It can be seen that the acylation reaction conventionally performed in an organic solvent capable of dissolving the reactant proceeds without using an organic solvent.

Example 5 A batch type autoclave having a capacity of 10 mL (SUS-316)
2-methoxy-5-nitroaniline (MNA)
4 mmol, tert-butylcarbonylacetic acid methyl ester (tBu-deriv) 4.8 mmol, and 4 g of dry ice were filled and sealed.
Heated at 0 ° C. for 1 hour. Next, the autoclave was put into a water bath, rapidly cooled to room temperature to stop the reaction, the autoclave was gradually opened, and the carbon dioxide sealed under pressure was released. The methanol produced by the reaction was distilled off, and the remaining components were supplemented with 4 g of dry ice, and heated again at 200 ° C. for 1 hour using a silicon oil bath. Next, the autoclave was put into a water bath and rapidly cooled to room temperature to stop the reaction. The acylated product as a target product was quantified by liquid chromatography, and the yield based on 2-methoxy-5-nitroaniline (MNA) was determined. The yield was 67.7%.

From the comparison between Examples 2 and 5, it can be seen that by removing methanol as a by-product during the reaction, the reaction proceeds and the yield can be increased.

[0042]

According to the present invention, an acylation reaction can be performed without using an organic solvent.

 ────────────────────────────────────────────────── ─── Continued on the front page (72) Inventor Satoru Ikesu 1 Sakuracho, Hino-shi, Tokyo Konica Corporation F-term (reference) 4H006 AA02 AC53 BB30 BB49 BC10 BC11 BE41 BJ20 BJ50 BV25 BV36 BV64

Claims (1)

[Claims] 1. An amino group of an amine compound represented by the following general formula [I] is acylated with an acylating agent represented by the following general formula [II] using carbon dioxide in a supercritical or subcritical state as a reaction medium. An acylation method characterized in that: General formula [I] Ar-NH ₂ [In the formula, Ar represents an aryl group or an aromatic heterocyclic group. General formula [II] R-COX [wherein, R represents an alkyl group, a cycloalkyl group or an alkenyl group, and X represents a leaving group. ]