JP2006182764A - New method for oxidizing primary or secondary alcohol - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a new method for oxidizing a primary or secondary alcohol. <P>SOLUTION: The new method for oxidizing the primary or secondary alcohol to produce the corresponding aldehyde or ketone is provided, involving using a nitroxy radical compound of the formula(1)(wherein, R<SP>0</SP>to R<SP>4</SP>are each a straight-chain or branched 1-10C alkyl, wherein two R<SP>0</SP>groups may be bound to each other to form a 5 to 7-membered heterocyclic ring together with the intramolecular nitrogen atom) and a co-oxidizing agent. In this process, the co-oxidizing agent to be used is an organic N-bromoamide compound or a combination of N-chlorosuccinimide with a bromide ion. <P>COPYRIGHT: (C)2006,JPO&NCIPI

Description

  The present invention relates to a novel process for the production of aldehydes or ketones by oxidizing primary or secondary alcohols.

  The reaction of oxidizing alcohols to aldehydes or ketones is listed as one of the most important reactions in organic synthesis. Oxidizing alcohol by using sodium hypochlorite as an oxidizing agent in the presence of a catalytic amount of 2,2,6,6-tetramethyl-1-piperidine-1-oxyl radical (hereinafter referred to as TEMPO) It is known that it can be performed (for example, refer nonpatent literature 1). It has also been reported that N-chloro compounds (Patent Document 1) such as N-chlorosuccinimide (hereinafter referred to as NCS) (Non-Patent Document 2) and trichloroisocyanuric acid can be used as the oxidizing agent.

Japanese Patent Laid-Open No. 9-169685 J. Org. Chem., 1987, 52, p.2529 J. Org. Chem., 1996, 61, p.7452

  As a result of intensive studies, the present inventors have found that by using a combination of an N-bromoamide compound or NCS and a bromide ion, an oxidation reaction of alcohol in an organic solvent catalyzed by a TEMPO derivative proceeds efficiently. The present invention has been completed.

（式中、Ｒ⁰ないしＲ⁴は、同一または異なって、直鎖状もしくは分岐状のＣ_1-10アルキル基を表し、または２つのＲ⁰は結合して分子内の窒素原子と共に５−７員の複素環を形成していてもよい。）
で表されるニトロキシラジカル化合物と共酸化剤を用い第１級または第２級アルコールを酸化し、アルデヒドまたはケトンを製造する方法において、
共酸化剤として、有機Ｎ−ブロモアミド化合物、あるいはＮ−クロロコハク酸イミドと臭化物イオンの組合せを用いることを特徴とする、アルデヒドまたはケトンを製造する方法に関する。 An object of the present invention is to provide a method for efficiently producing an aldehyde or a ketone by oxidizing a primary or secondary alcohol in an organic solvent.
That is, the present invention provides the following formula (1):

(Wherein R ⁰ to R ⁴ are the same or different and each represents a linear or branched C _1-10 alkyl group, or two R ⁰ are bonded together with a nitrogen atom in the molecule to form 5-7 It may form a membered heterocyclic ring.)
In a method for producing an aldehyde or a ketone by oxidizing a primary or secondary alcohol using a nitroxy radical compound represented by
The present invention relates to a method for producing an aldehyde or a ketone, wherein an organic N-bromoamide compound or a combination of N-chlorosuccinimide and bromide ions is used as a co-oxidant.

  According to the present invention, since it is a reaction in an organic solvent, the versatility of the reaction is enhanced by making the co-oxidant bromide without complicated pH adjustment and product decomposition. There is.

The catalyst used in this oxidation reaction is a compound represented by the above formula (1), but may have other substituents without departing from the scope of the present invention. For example, at least one of R ⁰ to R ⁴ may be a C _1-6 alkyl group substituted with a C _1-6 alkoxy group or the like.
The compound represented by the above formula (1) is a known compound and can be produced by the method described in European Patents 574666 and 574667, etc.

（式中、Ｒ¹ないしＲ⁴は上記と同じ基を表し、Ｒ⁵およびＲ⁶は、共に水素原子もしくはアルコキシ基を表すか、または一方は水素原子を表し、他方がヒドロキシル基、アルコキシ基、アシロキシ基、もしくはアシルアミノ基を表すか、あるいはＲ⁵とＲ⁶は一緒になって、式（ａ）〜（ｃ）

（上記式中Ｒ⁹はＣ_1-6アルキルを表し、Ｒ¹⁰およびＲ¹¹は、水素原子または同一もしくは異なって、Ｃ_1-6アルキル基を表す。）で示されるケタール基のいずれかを表す。） The catalyst (1) used in this reaction is preferably one represented by the following formula (1a).

(Wherein R ¹ to R ⁴ represent the same groups as described above, and R ⁵ and R ⁶ both represent a hydrogen atom or an alkoxy group, or one represents a hydrogen atom and the other represents a hydroxyl group, an alkoxy group, Represents an acyloxy group or an acylamino group, or R ⁵ and R ⁶ together represent a group represented by formulas (a) to (c):

(Wherein R ⁹ represents C _1-6 alkyl, and R ¹⁰ and R ¹¹ represent a hydrogen atom or the same or different and represent a C _1-6 alkyl group). . )

Particularly preferably, R ¹ to R ⁴ are methyl groups and R ⁵ and R ⁶ both represent a hydrogen atom, or one represents a hydrogen atom and the other represents a hydroxyl group, a methoxy group, an acetoxy group, a benzoyloxy group or This is the case with an acetamino group.

  The amount of the catalyst represented by the formula (1) used is preferably 0.01 to 30 mol%, particularly preferably 0.05 to 5 mol%, based on the alcohol as the substrate.

  Examples of the organic N-bromoamide compound suitable as a co-oxidant used in the present invention include N-bromoacetamide (hereinafter abbreviated as “NBA”) and N-bromosuccinimide (hereinafter abbreviated as “NBS”). , Tribromoisocyanuric acid, dibromodimethylhydantoin, N-bromophthalimide and the like. Of these, NBA and NBS are preferably used.

  As a bromide ion source when a combination of N-chlorosuccinimide and bromide ions is used as a co-oxidant, alkali bromides such as sodium bromide and potassium bromide, bromides such as tetrabutylammonium bromide and benzyltrimethylammonium bromide It is preferable to use a quaternary ammonium salt.

  When an organic N-bromoamide compound is used as a co-oxidant, it is preferably used in an amount of 1.05-2 equivalents, more preferably 1.1-1. 5 equivalents.

  On the other hand, when a combination of N-chlorosuccinimide and bromide ions is used as a co-oxidant, it is preferable to use 1.05-2 equivalents of the N-chlorosuccinimide with respect to the alcohol as the substrate, and more preferably. Is 1.1 to 1.5 equivalents. Further, bromide ions can be used in an amount of 1 to 100 mol%, preferably 5 to 20 mol%, based on the alcohol as a substrate.

  The alcohol used as a substrate in the present invention is not particularly limited as long as it is a compound having an alcoholic primary or secondary hydroxyl group, and specifically includes 1-octanol, 1-nonanol, 2-octanol and the like. Straight or branched primary or secondary alkyl alcohols, cycloalkyl alcohols such as cyclohexanol, cycloheptanol, phenethyl alcohol, benzyl alcohol, substituted or unsubstituted aralkyl such as p-methoxybenzyl alcohol Examples thereof include alcohol having a group. Glycerol acetonide is also preferably used.

  In the method of the present invention, it is not necessary to use water. In this case, an appropriate organic solvent can be appropriately used for the purpose of adjusting the viscosity, for example, tetrahydrofuran (hereinafter abbreviated as “THF”), diethyl ether, 1,2-diethoxyethane, methyl t-butyl ether. (Hereinafter abbreviated as “MTBE”), ester solvents such as ethyl acetate and butyl acetate, aromatic solvents such as benzene and toluene, hydrocarbon solvents such as hexane and heptane, acetone And ketone solvents such as methyl ethyl ketone, halogen solvents such as dichloromethane and 1,2-dichloroethane, and tertiary alcohols such as t-butanol and t-amyl alcohol. Preferred are ester solvents, ketone solvents, and halogen solvents.

  Although reaction temperature is not specifically limited, -50-100 degreeC is preferable, More preferably, it is -15-30 degreeC.

  A base may be used to neutralize hydrogen bromide by-produced by the oxidation reaction according to the present invention. In that case, as a preferable base, an inorganic base such as sodium acetate, sodium hydrogen carbonate, potassium carbonate, sodium phosphate, or potassium hydrogen phosphate, or an organic base such as triethylamine, diisopropylethylamine, or pyridine can be used. When the aldehyde of the product is unstable, an appropriate compound may be further reacted to derive a stable substance.

  When an optically active substance is used as the substrate alcohol, no significant racemization occurs in the oxidation method of the present invention, and a corresponding product maintaining optical activity is obtained.

  Hereinafter, the present invention will be described more specifically with reference to examples, but the present invention is not limited thereto. In each example, it was confirmed by analysis with a gas chromatograph that the product showed the same retention time as the standard product.

[Example 1]
Preparation of 1-octanal 2.0 g (15.4 mmol) of 1-octanol, 1.6 g (18.5 mmol) of sodium bicarbonate, 24 mg (0.15 mmol) of TEMPO, and 15 mL of dichloromethane were placed in a 50 mL eggplant flask. This suspension was placed in an ice bath to 10 ° C. or less, and 3.0 g (16.9 mmol) of NBS was added in three portions. Salts unnecessary for the solvent were removed by filtration, and the filtrate was washed with 5% aqueous sodium bicarbonate. The crude product was purified by distillation to obtain 1.74 g (yield 88%) of 1-octanal.

[Example 2]
Preparation of 1-octanal 2.0 g (15.4 mmol) of 1-octanol, 1.8 g (21.6 mmol) of sodium acetate, 53 mg (0.31 mmol) of 4-hydroxy TEMPO, and 15 mL of dichloromethane were placed in a 50 mL eggplant flask. This suspension was put in an ice bath to 10 ° C. or less, and 2.5 g (18.5 mmol) of NBA was added in two portions. Salts unnecessary for the solvent were removed by filtration, and the filtrate was washed with 5% aqueous sodium bicarbonate. The crude product was purified by distillation to obtain 1.78 g (yield 90%) of 1-octanal.

[Example 3]
Preparation of 1-octanal 2.0 g (15.4 mmol) of 1-octanol, 1.6 g (18.5 mmol) of sodium bicarbonate, 29 mg (0.15 mmol) of 4-methoxy TEMPO, 0.16 g (1.54 mmol) of sodium bromide ), 15 mL of 1,2-dichloroethane was placed in a 50 mL eggplant flask. This suspension was put in an ice bath to 10 ° C. or less, and 2.3 g (16.9 mmol) of NCS was added in two portions. Salts unnecessary for the solvent were removed by filtration, and the filtrate was washed with 5% aqueous sodium bicarbonate. The crude product was purified by distillation to obtain 1.67 g (yield 85%) of 1-octanal.

[Example 4]
Preparation of 1-hexanal 2.0 g (19.6 mmol) of 1-hexanol, 1.2 g (11.8 mmol) of sodium carbonate, 42 mg (0.20 mmol) of 4-acetamino TEMPO, and 15 mL of dichloromethane were placed in a 50 mL eggplant flask. This suspension was put in an ice bath to 10 ° C. or lower, and 3.8 g (21.6 mmol) of NBS was added in four portions. Salts unnecessary for the solvent were removed by filtration, and the filtrate was washed with 5% aqueous sodium bicarbonate. The crude product was purified by distillation to obtain 1.77 g (yield 90%) of 1-hexanal.

[Example 5]
Preparation of phenylacetaldehyde β-phenethyl alcohol (2.0 g, 16.4 mmol), sodium acetate (2.0 g, 24.6 mmol), TEMPO (26 mg, 0.16 mmol), and ethyl acetate (15 mL) were placed in a 50 mL eggplant flask. This suspension was put in an ice bath to 10 ° C. or less, and 3.2 g (18.0 mmol) of NBS was added in two portions. Salts unnecessary for the solvent were removed by filtration, and the filtrate was washed with 5% aqueous sodium bicarbonate. The crude product was purified by distillation to obtain 1.67 g (yield 85%) of phenylacetylaldehyde.

[Example 6]
Preparation of 2-octanone 2.0 g (15.4 mmol) of 2-octanol, 1.6 g (18.5 mmol) of sodium hydrogen carbonate, 24 mg (0.15 mmol) of TEMPO, 15 mL of 1,2-dichloroethane were placed in a 50 mL eggplant flask. It was. This suspension was placed in an ice bath to 10 ° C. or less, and 3.0 g (16.9 mmol) of NBS was added in two portions. Salts unnecessary for the solvent were removed by filtration, and the filtrate was washed with 5% aqueous sodium bicarbonate. The crude product was purified by distillation to obtain 1.88 g (yield 95%) of 2-octanone.

[Example 7]
Preparation of cyclohexanone 2.0 g (20 mmol) of cyclohexanol, 1.3 g (12 mmol) of sodium carbonate, 43 mg (0.2 mmol) of 4-acetamino TEMPO, and 15 mL of THF were placed in a 50 mL eggplant flask. To this suspension, 3.9 g (22 mmol) of NBS was added in two portions. Salts unnecessary for the solvent were removed by filtration, and the filtrate was washed with 5% aqueous sodium bicarbonate. The crude product was purified by distillation to obtain 1.73 g (88% yield) of cyclohexanone.

[Example 8]
Preparation of benzaldehyde benzyl alcohol 2.0 g (18.5 mmol), potassium carbonate 1.5 g (11.1 mmol), 4-hydroxy TEMPO 31 mg (0.19 mmol), tetrabutylammonium bromide 0.5 g (1.9 mmol), MTBE 15 mL was placed in a 50 mL eggplant flask. This suspension was put in an ice bath to 10 ° C. or lower, and 2.7 g (20.4 mmol) of NCS was added in three portions. Salts unnecessary for the solvent were removed by filtration, and the filtrate was washed with 5% aqueous sodium bicarbonate. The crude product was purified by distillation to obtain 1.77 g (yield 90%) of benzaldehyde.

[Example 9]
Preparation of p-anisaldehyde p-methoxybenzyl alcohol 2.0 g (14.5 mmol), sodium carbonate 0.9 g (8.7 mmol), TEMPO 23 mg (0.15 mmol), benzyltrimethylammonium bromide 0.3 g (1.5 mmol) ), 15 mL of dichloromethane was placed in a 50 mL eggplant flask. This suspension was put in an ice bath to 10 ° C. or less, and NCS 2.1 g (16 mmol) was added in two portions. Salts unnecessary for the solvent were removed by filtration, and the filtrate was washed with 5% aqueous sodium bicarbonate. The crude product was purified by distillation to obtain 1.62 g (yield 82%) of p-anisaldehyde.

[Example 10]
Preparation of methyl (R) -3- (2,2-dimethyl-1,3-dioxolan-4-yl) -2-propenoate (R) -glycerol acetonide 5.0 g (37.8 mmol), hydrogen carbonate Sodium 4.8 g (56.7 mmol), 4-acetoxy TEMPO 41 mg (0.19 mmol), and THF 50 mL were placed in a 200 mL three-necked flask. This suspension was placed in an ice bath to 10 ° C. or less, and 8.1 g (45.4 mmol) of NBS was added in three portions. Salts insoluble in the solvent were removed by filtration, the filtrate was cooled to 0 ° C., 15.1 g (45.4 mmol) of methyl triphenylphosphoranylidene acetate was added, and the mixture was stirred at 0 ° C. for 16 hours. Hexane 100mL was added to the reaction liquid, the insoluble matter was removed by filtration, and the filtrate was concentrated. The crude product was purified by silica gel chromatography to obtain 5.3 g (yield 75%) of the desired ester in a ratio of trans isomer / cis isomer = 29/71.

  INDUSTRIAL APPLICABILITY The present invention can be effectively used in the field of organic synthetic chemical industry in which a primary or secondary alcohol is used as a raw material and an aldehyde or ketone is produced by an oxidation reaction thereof.

Claims (8)

Following formula (1)

(Wherein R ⁰ to R ⁴ are the same or different and each represents a linear or branched C _1-10 alkyl group, or two R ⁰ are bonded to each other together with a nitrogen atom in the molecule to form 5-7 It may form a membered heterocyclic ring.)
In a method for producing an aldehyde or a ketone by oxidizing a primary or secondary alcohol in an organic solvent using a nitroxy radical compound represented by
A method for producing an aldehyde or a ketone characterized by using an organic N-bromoamide compound or a combination of N-chlorosuccinimide and bromide ions as a co-oxidant. Nitroxy radical compounds are represented by the general formula (1a)

(Wherein R ¹ to R ⁴ represent the same group as in claim 1, R ⁵ and R ⁶ both represent a hydrogen atom or a C _1-6 alkoxy group, or one represents a hydrogen atom and the other represents Represents a hydroxyl group, a C _1-6 alkoxy group, an acyloxy group, or an acylamino group, or R ⁵ and R ⁶ together represent a group represented by the formulas (a) to (c):

(Wherein R ⁹ represents C _1-6 alkyl, and R ¹⁰ and R ¹¹ are a hydrogen atom or the same or different and each represents a C _1-6 alkyl group). . )
The method of Claim 1 which is a compound represented by these. In the nitroxy radical compound (1a), R ¹ to R ⁴ represent a methyl group, and R ⁵ and R ⁶ are both hydrogen atoms, or one is a hydrogen atom and the other is a hydroxyl group, a methoxy group, an acetoxy group, The method according to claim 2, which is a benzoyloxy group or an acetamino group.   The method according to any one of claims 1 to 3, wherein the co-oxidant is an organic N-bromoamide compound.   The method according to claim 4, wherein the organic N-bromoamide compound is N-bromosuccinimide or N-bromoacetamide.   The method according to claim 1, wherein the cooxidant is a combination of N-chlorosuccinimide and bromide ions.   The method of claim 6 wherein the bromide ion source is an alkali metal bromide or bromide quaternary ammonium salt.   The method of claim 6 wherein the bromide ion source is sodium bromide or potassium bromide.