JP2002265409A - Method for manufacturing carbonium compound - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a method for manufacturing a carbonyl compound, advantageous in point of operability and manufacturing cost, and having a wide application. SOLUTION: The method for manufacturing a carbonyl compound expressed by general formula (I) is carried out by acting an oxidant on a compound expressed by general formula (II) [wherein, R<1> and R<2> are identical to or different from each other, and they are each H, a (substituted) alkyl, a (substituted) aryl, a (substituted) heteroaryl or a (substituted) aralkyl] in a binary phase mixed solvent consisting of a non-water miscible organic solvent and water in the presence of a phase transfer catalyst under keeping the aqueous phase weakly basic.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a method for producing a carbonyl compound in which a hydroxyl group of an alcohol is oxidized using an oxidizing agent in a two-phase mixed solvent in the presence of a phase transfer catalyst.

[0002]

2. Description of the Related Art A method for obtaining a carbonyl compound by oxidizing a hydroxyl group of a compound having a hydroxyl group such as an alcohol with an oxidizing agent is an effective industrial production method from the viewpoint of production cost and operability. Among the production methods, the following two types are known as methods using hypochlorite as an oxidizing agent. (A) A method in which hypochlorite and a substrate are mixed and reacted under acidic conditions (see JP-A-63-145248 and JP-A-8-176055). A method in which substrates are mixed and the reaction is carried out under the conditions of a phase transfer reaction (Isreal. Journal.
Chemistry. , 26 , 229 (1985))

However, of the above-mentioned methods,
The method (a) cannot be applied to a water-insoluble substrate.
Since the reaction was oxidized with hypochlorous acid under acidic conditions, it was difficult to control the reaction, the substrate was limited, and it could not be said that this was a general method for producing a carbonyl compound. Also,
In the method (b), since the oxidation reaction is performed with the pH value of the hypochlorous acid solution, sufficient oxidizing power may not be obtained,
It could only be applied to limited substrates. As another method, a method using a resin catalyst (J. Org. Chem., 47 , 365 (198)
Although 2)) is also known, the amount of the resin catalyst used is large and it is not a practical method.

As described above, the conventional method gives good results for substrates that are easily oxidized such as benzyl alcohol and cycloalkanol and stable substrates, but gives good results for substrates such as linear alkane hydroxide. In many cases, a satisfactory yield cannot be obtained, and it cannot always be said that this is a general production method.

[0005]

SUMMARY OF THE INVENTION The present invention has been made in view of the above circumstances, and has as its object to provide a method for producing a carbonyl compound which is advantageous in operability and production cost and has high generality. Aim.

[0006]

Means for Solving the Problems The present inventors have conducted intensive studies on an industrially advantageous method for producing a carbonyl compound, and have found that an oxidizing agent is added to a compound having a hydroxyl group in the presence of a phase transfer catalyst under a weak alkaline condition. The inventors have found that a carbonyl compound can be obtained very easily and in good yield by acting, and have completed the present invention.

That is, the present invention provides a compound represented by the general formula (II):

[0008]

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(Wherein R ¹ and R ² are the same or different and each represent a hydrogen atom, an alkyl group which may have a substituent, an aryl group which may have a substituent, Represents an optionally substituted heteroaryl group or an optionally substituted aralkyl group.) In a two-phase mixed solvent containing a non-water-miscible organic solvent and water. General formula (I) characterized in that an oxidizing agent acts to make an aqueous phase weakly alkaline in the presence of a catalyst.

[0010]

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(Wherein R ¹ and R ² have the same meanings as described above). In the present invention, as the phase transfer catalyst, a general formula (III)

[0012]

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(Wherein R^a, R^b, R^cAnd R^dEach
Each independently represents an alkyl group or an aralkyl group;
⁺Represents an onium cation containing a nitrogen atom or a phosphorus atom.
Represents, B⁻Indicates an anion for neutralizing the cation.
You. It is preferable to use an onium salt represented by
A compound represented by the formula (III):^a, R^b,
R^c, R ^dCarbon of the alkyl or aralkyl group represented by
It is more preferable to use an onium salt whose total number is 4 to 30.
preferable. In the present invention, hypoxia is used as the oxidizing agent.
It is preferable to use a halogenate,
It is preferred to carry out the reaction at a temperature of 0 ° C.

[0014]

BEST MODE FOR CARRYING OUT THE INVENTION The present invention provides a compound represented by the general formula (II) containing a non-water-miscible organic solvent and water.
In a phase-based mixed solvent, in the presence of a phase transfer catalyst, the aqueous phase is made weakly alkaline to act on an oxidizing agent. A method for producing a carbonyl compound represented by the general formula (I), characterized by the following.

In the above general formulas (I) and (II), R
¹ and R ² are the same or different and each represents a hydrogen atom, an alkyl group which may have a substituent, an aryl group which may have a substituent, or a heteroaryl group which may have a substituent Or an aralkyl group which may have a substituent.

The alkyl group of the alkyl group which may have a substituent includes, for example, methyl, ethyl, n-
Propyl, isopropyl, n-butyl, isobutyl, t
-Alkyl groups having 1 to 20 carbon atoms such as -butyl, n-pentyl, n-hexyl, cyclopentyl, cyclohexyl, octyl, and eicosanyl groups. Examples of the aryl group of the aryl group which may have a substituent include a phenyl group, a 1-naphthyl group, and a 2-naphthyl group. Examples of the heteroaryl group of the heteroaryl group which may have a substituent include, for example, 2-pyridyl group, 3-pyridyl group, 4-pyridyl group, 2-imidazolyl group, 4-imidazolyl group, 5-imidazolyl Groups, 3-pyrazolyl group, 4-pyrazolyl group, 5-pyrazolyl group, 2-indolyl group, 3-indolyl group, quinolyl group and the like. Examples of the aralkyl group of the aralkyl group which may have a substituent include a benzyl group, a phenyl group, a 3-phenylpropyl group, a diphenylmethyl group and the like.

The alkyl group, aryl group, heteroaryl group and aralkyl group may have 1 to 3 identical or different substituents. Examples of such a substituent include halogen atoms such as fluorine, chlorine, bromine and iodine;
Methyl, ethyl, n- propyl, isopropyl, n- butyl, isobutyl, t- butyl, n- pentyl, _{C 1-6} alkyl group such as n- hexyl; methoxy, ethoxy, n- propoxy, isopropoxy, n- Butoxy,
A C _1-20 alkoxy group such as isobutoxy, t-butoxy, n-pentoxy, benzyloxy group; formyl,
An amino group having a protecting group such as an alkylcarbonyl, phenylcarbonyl, alkoxycarbonyl, phenylsulfonyl, or alkylsulfonyl group; an alkylamino group optionally having a substituent; an arylamino group optionally having a substituent; An aralkylamino group which may have a substituent;

Examples of the alkyl group of the alkylamino group which may have a substituent include, for example, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, t-butyl, n-pentyl, n-pentyl Examples thereof include an alkyl group having 1 to 20 carbon atoms such as hexyl, cyclopentyl, cyclohexyl, octyl, and eicosanyl. Examples of the aryl group of the arylamino group optionally having a substituent include a phenyl group, a 1-naphthyl group,
And a 2-naphthyl group. As the aralkyl group of the aralkylamino group which may have a substituent,
For example, a benzyl group, a phenyl group, a 3-phenylpropyl group, a diphenylmethyl group and the like can be mentioned.

The alkyl group, aryl group and aralkyl group may have 1 to 3 identical or different substituents. Such substituents include, for example, fluorine,
Halogen atoms such as chlorine, bromine and iodine; C _1-6 alkyl groups such as methyl, ethyl, n-propyl, isopropyl, n-butyl, peroxobutyl, t-butyl, n-pentyl and n-hexyl groups; methoxy and ethoxy , N-propoxy, isopropoxy, n-butoxy, isobutoxy,
C such as t-butoxy, n-pentoxy, benzyloxy, etc.
_1-20 alkoxy group; and the like.

The amino group having a protecting group, the alkylamino group which may have a substituent, the arylamino group which may have a substituent and the aralkylamino group which may have a substituent Preferred specific examples include benzoylamino, tosylamino, methoxycarbonylamino, N-methyl-benzoylamino, N-methyl-tosylamino, N-methyl-methoxycarbonylamino,
-Benzyl-benzoylamino, N-benzyl-tosylamino, N-benzyl-methoxycarbonylamino, N
-Phenyl-methoxycarbonylamino group and the like.

The present invention is carried out in a two-phase mixed solvent containing a non-water-miscible organic solvent and water. As the non-water-miscible organic solvent used in the reaction, any organic solvent that is immiscible with water (not compatible) can be used without any particular limitation. For example, ether solvents such as diethyl ether and diisopropyl ether; chlorine solvents such as chloroform, dichloromethane and carbon tetrachloride; benzene, toluene,
Hydrocarbon solvents such as xylene, n-pentane, n-hexane, n-heptane and cyclohexane; methyl acetate;
Ester solvents such as ethyl acetate and n-propyl acetate; Among these, use of a hydrocarbon solvent such as toluene is preferred from the viewpoint of easy handling. These can be used alone or in combination of two or more.

The amount of the non-water-miscible organic solvent used is usually 1 to 100 (W / V) of the compound represented by the general formula (II),
It is preferably in the range of 5 to 20 (W / V). The mixing ratio between the non-water-miscible organic solvent and water (aqueous solution of hypohalite) is usually from 1: 100 to 100: 1 by volume.
Preferably it is in the range of 10: 100 to 100: 10.

As the phase transfer catalyst used in the present invention, it is preferable to use the compound represented by the general formula (III). In the formula (III), R ^a , R ^b , R ^c and R ^d each independently represent one group selected from an alkyl group and an aralkyl group, and A ⁺ represents a nitrogen atom or a phosphorus atom. Represents an onium cation, and B ⁻ represents an anion for neutralizing the cation.

The alkyl groups of R ^a , R ^b , R ^c and R ^d include, for example, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, t-butyl, n-
1-2 carbon atoms such as pentyl, n-hexyl, cyclopentyl, cyclohexyl, n-octyl and eicosanyl groups
And an alkyl group of 0. As an aralkyl group,
For example, an aralkyl group having 7 to 13 carbon atoms, such as a benzyl group, a phenyl group, a 3-phenylpropyl group, and a diphenylmethyl group. ^{Furthermore, R a, R b, R} c, the total number of carbon atoms of R ^d is more preferably 4 to 30.

[0025] As ^R a ^R b ^R c ^R d onium cation represented by ^{A +,} for example, quaternary ammonium ions or phosphonium ions, and the like. As the anion represented by B ⁻ , for example, a chloride ion (Cl
⁻ ), Bromide ion (Br ⁻ ), iodide ion (I ⁻ ), HSO ₄ ⁻ , BF ₄ ⁻ , and ClO ₄ ⁻ .

The compound represented by the general formula (III) includes, for example, quaternary ammonium salts such as benzyltrialkylammonium halide and benzyltrialkylammonium hydroxide; tetrabutylphosphonium chloride, tetrabutylphosphonium bromide, Phosphonium salts such as benzyltrimethylphosphonium chloride and benzyltrimethylphosphonium bromide; and the like.

Of these, in the present invention, it is preferable to use a quaternary ammonium salt from the viewpoints of easy availability, handleability and giving the desired product in high yield. Such quaternary ammonium salts include, for example, benzyltrimethylammonium chloride, benzyltrimethylammonium bromide, benzyltrimethylammonium hydroxide, benzyltrimethylammonium hydrosulfide, benzyltriethylammonium chloride,
Benzyltriethylammonium bromide, benzyltriethylammonium hydroxide, benzyltriethylammonium hydrosulfide, benzyltripropylammonium chloride, benzyltripropylammonium bromide, benzyltripropylammonium hydroxide, benzyltripropylammonium hydrosulfide, benzyltributylammonium chloride, Benzyltributylammonium bromide, benzyltributylammonium hydroxide, benzyltributylammonium hydrosulfide, tetrabutylammonium chloride, tetrabutylammonium bromide, tetrabutylammonium hydroxide, tetrabutylammonium hydrosulfide, trio Chill ammonium chloride,
Trioctylmethylammonium bromide, trioctylmethylammonium hydrosulfide, trioctylmethylammonium hydroxide and the like can be used. The amount of the phase transfer catalyst to be used is in the range of 0.1 to 20 mol%, preferably 0.5 to 10 mol%, based on the compound represented by the general formula (II).

The oxidizing agent used in the present invention is preferably a hypohalite or an aqueous solution thereof, more preferably an alkali metal salt of hypohalous acid or an alkaline earth metal salt of hypohalous acid, or an aqueous solution thereof. . Examples of the alkali metal salt of hypohalous acid or alkaline earth metal salt of hypohalous acid or an aqueous solution thereof include sodium hypochlorite, potassium hypochlorite, calcium hypochlorite, and hypobromite. Examples include soda, potassium hypobromite, calcium hypobromite, and aqueous solutions thereof. Among them, it is particularly preferable to use a commercially available aqueous solution of sodium hypochlorite from the viewpoint of availability and handleability. The amount of the oxidizing agent used is usually 100 mol% based on the compound represented by the general formula (II).
１，1,000 mol%, preferably 100 mol% 〜500
Mol% range.

The present invention is characterized in that the reaction is carried out in a two-phase mixed solvent containing a non-water-miscible organic solvent and water while adjusting and maintaining the pH of the aqueous phase to be slightly alkaline. That is,
A predetermined amount of an acid is added to a two-phase mixed solvent solution of the compound represented by the general formula (II), the phase transfer catalyst, and the oxidizing agent under stirring to adjust the pH of the aqueous phase to be slightly alkaline and to carry out the reaction. .
In the present invention, weak alkalinity means that the pH value of the aqueous phase is 7 to 11, preferably 9 to 10.

For example, when a commercially available sodium hypochlorite is used as the oxidizing agent, the pH value of the aqueous sodium hypochlorite solution (corresponding to the aqueous phase in this reaction) is initially about 12, and By adding an acid to the phase, the reaction is carried out while adjusting and maintaining the alkalinity to be weakly alkaline. At this time, it is preferable to control the amount and rate of dropping of the acid so that the aqueous phase maintains weak alkalinity.

The acid used for the pH adjustment is not particularly limited as long as it is a common acid such as acetic acid, hydrogen chloride, sulfuric acid and the like, but hydrochloric acid is preferred from the viewpoint of ease of use. The concentration of the aqueous solution of these acids is not particularly limited, and an acid having a predetermined concentration can be appropriately used.

The reaction is usually carried out at 0 ° C. to 50 ° C., preferably at 1 ° C.
It is performed in a temperature range of 0 ° C to 30 ° C. The reaction time is generally 0.5 hour to 24 hours, preferably 1 to 6 hours.
After completion of the reaction, the compound represented by the general formula (I) can be easily obtained as a non-water-miscible organic solvent solution by separating the reaction mixture. Further, the compound represented by the general formula (I) can be isolated from the non-water-miscible organic solvent solution by ordinary separation and purification means.

[0033]

Next, the present invention will be described in more detail with reference to Reference Examples and Examples. Note that the present invention is not limited to these.

Example 1 Production of 1-benzyloxy-2-butanone 2 ml of toluene, 1.7 N aqueous sodium hypochlorite solution 2
ml (3.4 mmol), 180 mg (1.00 mmol) of 1-benzyloxy-2-butanol and 32 mg (0.1 mmol) of tetrabutylammonium bromide.
1) Hydrochloric acid was added dropwise with stirring to the mixed solution of
The H value was adjusted to 10, and the mixture was further stirred at 20 ° C. for 1 hour.
After completion of the reaction, the reaction solution was separated to separate an organic layer, and the organic layer was washed with a sodium thiosulfate solution. The residue obtained by concentrating the organic layer was subjected to silica gel column chromatography (eluent: ethyl acetate / n-hexane = 1/9 to 1 /
By purifying in 4), 164 mg of the title compound was obtained. Yield: 92%

(Comparative Example 1) Oxidation reaction of 1-benzyloxy-2-butanol 2 ml of toluene, 1.7N aqueous sodium hypochlorite solution 2
ml (3.4 mmol), 180 mg (1.00 mmol) of 1-benzyloxy-2-butanol and 32 mg (0.1 mmol) of tetrabutylammonium bromide.
l) The mixed solution of 2)
After stirring at 0 ° C. for 1 hour, the oxidation reaction had not progressed at all.

Example 2 α- (N-benzoyl-N-
Production of methyl) aminopropiophenone 1 ml of toluene, 1.0 ml (1.7 mmol) of 1.7N aqueous sodium hypochlorite solution, Anti-2- (N-
135 mg (0.50 mmol) of benzoyl-N-methyl) amino-1-phenylpropanol and 16 mg (0.05 mmol) of tetrabutylammonium bromide
1) Hydrochloric acid was added dropwise with stirring to the mixed solution of
The H value was adjusted to 10, and the mixture was further stirred at 20 ° C. for 4 hours.
After completion of the reaction, the reaction solution was separated to separate an organic layer, and the organic layer was washed with a sodium thiosulfate solution. The residue obtained by concentrating the organic layer was subjected to silica gel column chromatography (eluent: ethyl acetate / n-hexane = 1/9 to 1 /
Purification according to 4) afforded 126 mg of the title compound. Yield: 94%

Comparative Example 2 Oxidation of Anti-2- (N-benzoyl-N-methyl) amino-1-phenylpropanol 1 ml of toluene 1.0 ml (1.7 mmol) of 1.7N aqueous sodium hypochlorite solution , Anti-2- (N-
135 mg (0.50 mmol) of benzoyl-N-methyl) amino-1-phenylpropanol and 16 mg (0.05 mmol) of tetrabutylammonium bromide
l) The mixed solution of 2)
After stirring at 0 ° C. for 4 hours, the oxidation reaction had not progressed.

[0038]

As described above, according to the present invention,
There is provided a method for producing a carbonyl compound which is advantageous in operability and production cost and has high generality.

Continuing from the front page (72) Inventor Tsutomu Inoue 345 Takada, Odawara-shi, Kanagawa F-term in the Soda Research Laboratories of Nippon Soda Co., Ltd. 4H006 AA02 AC44 BA51 BA65 BB31 BB46 BC10 BC16 BE36 BJ50 BR30 BV72 4H039 CA65 CC20

Claims (6)

[Claims] 1. A compound of the general formula (II) (Wherein R ¹ and R ² are the same or different and each have a hydrogen atom, an alkyl group which may have a substituent, an aryl group which may have a substituent, A heteroaryl group or an aralkyl group optionally having substituent (s)) in a two-phase mixed solvent containing a non-water-miscible organic solvent and water in the presence of a phase transfer catalyst. Wherein the aqueous phase is made weakly alkaline and an oxidizing agent is allowed to act thereon, characterized by the following general formula (I): (Wherein, R ¹ and R ² have the same meanings as described above). 2. The phase transfer catalyst of the general formula (III): ## STR3 ## (Wherein, R ^a , R ^b , R ^c and R ^d each independently represent an alkyl group or an aralkyl group, A ⁺ represents an onium cation containing a nitrogen atom or a phosphorus atom, and B ⁻ represents a cation The method for producing a carbonyl compound according to claim 1, wherein an onium salt represented by the following formula: 3. The compound of the formula (III) as the phase transfer catalyst
A compound represented by the formula:^a, R ^b, R^cAnd R^dIn table
The total number of carbon atoms of the alkyl or aralkyl group
3. An onium salt having a molecular weight of from 30 to 30 is used.
A method for producing a carbonyl compound. 4. The method for producing a carbonyl compound according to claim 1, wherein a hypohalite is used as the oxidizing agent. 5. The process for producing a carbonyl compound according to claim 1, wherein the reaction is carried out by adjusting the pH value of the aqueous phase to 7 to 11. 6. The method according to claim 1, wherein the reaction temperature is 0 ° C. to 50 ° C.
5. The method for producing a carbonyl compound according to any one of 5.