JPH0977705A - Oxidation agent for alcohol and oxidation using the same - Google Patents

Abstract

PROBLEM TO BE SOLVED: To produce a corresponding carbonyl compound by oxidizing an alcohol with a halogen acid in high conversion and selectivity. SOLUTION: A primary or secondary alcohol is oxidized using an oxidizing agent comprising a halogen acid of the formula: M(XO3 )n (M is hydrogen atom or metal; X is a halogen atom; n is 1 or shows the valence of the metal M) or its salt (bromic acid, iodic acid or their alkali metal salt) and a reducing inorganic compound (sulfite, hydrogensulfite, thiosulfate or pyrosulfite) to give the corresponding carbonyl compound stoichiometrically. The oxidative esterification of a primary alcohol gives the corresponding ester and carboxylic acid, a secondary alcohol gives the corresponding ketone and an α,ω-diol gives the corresponding lactone or dicarboxylic acid.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to an alcohol oxidation reaction agent useful for producing an ester, a ketone, a lactone or a dicarboxylic acid from an alcohol in a liquid phase oxidation reaction, and an alcohol oxidation method using this catalyst. Regarding

[0002]

2. Description of the Related Art Halogen acids and their salts (hereinafter sometimes referred to as "halogen acids") have been used for a long time as industrially useful oxides, and not only oxidation of alcohols but also aldehydes It is known to exhibit high activity in reactions such as the oxidation of olefins, the oxidation of olefins and paraffins, oxidative dehydrogenation, and oxidative cleavage. In addition to the above-mentioned halogen acids, halogens, hypohalogen acid salts, perhalogen acids, halogen acid fluorides, N-halogen acid amides, hypohalous acid esters, iodosyl compounds, etc. are often used as halogens as an oxidizing agent. Has been done. Halogen acids are relatively inexpensive oxides that can be used for all oxidation reactions, are easy to handle, and are extremely safe compared to typical air oxidation and oxidation reactions using peroxides. Moreover, there is an advantage that it is easy to control. Also, since the reaction proceeds stoichiometrically,
The reaction can be controlled by the amount used, and there is also an advantage that high oxidation selectivity, which is difficult with other general oxidation reactions, can be obtained. Therefore, the oxidation method using the halogen acids is industrially highly value-added compounds (for example, pharmaceuticals,
It is used as an effective means for small-quantity batch production of pesticides, etc.

There are three main methods of using halogen acids as oxidizing agents, namely, (1) a method using halogen alone or in an organic solvent, and (2) a method using hypohalous acid in an acidic solution. , (3) Alkali or carbonate and halogen are used as hypohalite. Of these methods, the method (1) uses a large amount of halogen gas, and thus requires a large-scale detoxification facility due to environmental problems, and will be subject to legal restrictions in the future. There is a strong possibility. Further, in the method (2), since it is necessary to make the reaction system acidic, a side reaction often occurs, and the selectivity of the oxidation reaction product decreases. Furthermore, since the decomposition efficiency to hypohalous acid, which is an oxidizing active species, is small under acidic conditions, it is usually 3 to 3 to the oxidant (substrate).
An excess of 10 times molar amount of halogen acids is required,
It is economically disadvantageous. On the other hand, the method (3) is
Since the oxidizing active species are present in the form of a relatively stable salt, they are easy to handle and have the advantage that a slight excess amount of hypohalite with respect to the substrate may be used.

Therefore, with respect to the above method (3), several improvements in the oxidation technique have been proposed. For example, JP-A-62-155225 discloses magnesium, aluminum, chromium, manganese, iron, nickel as an activator for bromic acid or a salt thereof in an alkaline medium.
A method of adding copper, zinc, ruthenium alone or a salt of these metals (sulfate, carbonate, nitrate, hydrochloride, phosphate) and oxidizing hydrocarbons or alcohols in a liquid phase is disclosed. There is. This document describes an example of producing a diketone, a lactone or the like from a diol. Further, JP-A-1-151532 and JP-A-1-15132
Japanese Patent No. 51534 discloses a method of producing a ketone or an aldehyde by reacting a solid bromate with an alcohol in an inert organic solvent insoluble in water in the presence of alumina or silica gel.

However, these methods have a low oxidation yield of about 50% to 80% except for some alcohol substrates,
A purification process after the reaction is required. Moreover, since various metals and heavy metal compounds are added, special equipment is required for waste treatment after the reaction.

On the other hand, in the oxidation reaction of diols, industrially extremely useful compounds such as diketones, dialdehydes, dicarboxylic acids, ketoaldehydes, keto acids, lactones, ketol alcohols and hydroxy aldehydes are obtained. Therefore, various oxidation methods have been studied for diols, and methods for selectively producing the oxidation reaction product have been attempted. For example, in addition to the method using halogen or a halogen-containing compound, as a general method for oxidizing an alcohol compound, (1) a radical method using molecular oxygen as an oxidant, (2) chromic acid, manganic acid, etc. Techniques using metal oxides, (3) techniques using solid acid catalysts that are complex metal species, (4) techniques using organic or inorganic peroxides, (5) metal complexes using carbonyl compounds as hydrogen acceptors A method by ligand exchange on a complex has been studied. However, in the oxidation of diols, the above-mentioned general methods are not widely applicable due to the necessity of controlling the reaction, and the reaction conditions are severely limited even when these methods are applicable. Also,
In the oxidation method of diols, various combinations of oxidation products can be obtained. Therefore, in order to avoid the complexity of treatment / purification after the reaction, high conversion rate and reaction selectivity are required in the oxidation reaction.

From these points, diols are often oxidized by a very special oxidation system. For example, as an oxidation method for producing a corresponding diketone from diols,
Oxidation with chromium (VI) oxide-pyridine complex [Sarett
Method, Cornforth method], DMSO oxidation method, NaIO ₃ and K
An oxidation method using IO ₃ , a Pt / O ₂ air oxidation method and the like are known. Further, as an oxidation method for producing a corresponding keto alcohol from diols, a method using lead tetraacetate / pyridine and a method using hypohalous acid / ammonium nitrate salt are also known. All of these methods are effective oxidation methods, since the target compounds can be produced with relatively high reaction efficiency and selectivity. on the other hand,
In the oxidation reaction of vicinal diols having a hydroxyl group bonded to an adjacent carbon atom, cleavage of the carbon-carbon bond (glycol cleavage) is likely to occur during the oxidation process, so that the corresponding 1,2-diketone or acyloin can be selectively selected. Is particularly difficult to generate. Therefore, in order to increase the selectivity, an excess amount of silver carbonate / Celite reagent is used in Fetizon.
Only limited methods such as law can be adopted.

As described above, there are very few general-purpose oxidation methods for various alcohols, and in particular, a general-purpose oxidation method using halogen acids, which are industrially advantageous oxidizing agents, has not been established.

Regarding the stoichiometric reaction with halogen acids, by using H ₅ IO ₆ or NaBrO ₃ and NaHSO ₃ , the corresponding halohydrin derivative can be obtained in high yield from unsaturated hydrocarbons such as olefins. (J. Org. Chem., 59, 5550-5555 (1994)). In this method, for example, the corresponding halohydrin is produced from an olefin, the corresponding α-haloaldol is produced from an α, β-unsaturated carbonyl compound, and the corresponding 2-halo-1,3-diol is produced from allyl alcohol. However, the corresponding ketone, diketone or α, α-dihaloketone can be produced in high yield from the alkyne.

[0010]

SUMMARY OF THE INVENTION It is an object of the present invention to provide a reactant which can oxidize alcohols using halogen acids with high reactivity and selectivity, and an oxidation method using the same. Another object of the present invention is to provide a reactant capable of oxidizing alcohols with a stoichiometrically high conversion rate and selectivity even under mild conditions, and an oxidation method using the same. Still another object of the present invention is to provide an oxidation reaction agent which is versatile for various alcohols and an oxidation method using the same.

[0011]

Means for Solving the Problems As a result of intensive studies to achieve the above-mentioned object, the present inventors have found that NaBrO ₃ / NaH
When the SO ₃ oxidation system was applied to the oxidation reaction of alcohols such as primary alcohols and α, ω-diols, esters were produced from the primary alcohols by oxidative esterification, and α, ω-diols were converted into corresponding cyclic compounds. The inventors found that the respective esters were produced in high yields, and after further studies, completed the present invention.

That is, the alcohol oxidizing agent according to the present invention has the following formula M (XO ₃ ) _n (wherein M is a hydrogen atom or a metal, X is a halogen atom, n is 1 or a valence of the metal M). (Indicating the number) or a salt thereof and a reducing inorganic compound. The halogen acid or a salt thereof, M is a hydrogen atom or a trivalent metal, X is a chlorine, bromine or iodine atom, n is an integer halogen acid of 1 to 3 or a salt thereof, for example, chloric acid, bromic acid or It may be iodic acid or a salt thereof. The reducing inorganic compound, for example, sulfite,
Examples include bisulfite, thiosulfate, and pyrosulfite. The ratio of the reducing inorganic compound to 1 equivalent of the halogen acid or its salt may be selected from the range of, for example, about 0.1 to 5 equivalents.

In the method of the present invention, primary or secondary alcohol is oxidized by the above-mentioned oxidation reaction agent. In this method, monohydric or polyhydric alcohols can be oxidized in the liquid phase. By utilizing the oxidation reaction, various corresponding carbonyl compounds can be produced depending on the type of alcohol and the substitution site of the hydroxyl group. For example, the corresponding ester or carboxylic acid can be produced from a primary alcohol, the corresponding ketone can be produced from a secondary alcohol, and the corresponding lactone or dicarboxylic acid can be produced from a diol. Furthermore, in the method of the present invention, chloric acid, bromic acid, iodic acid or salts thereof,
A method of oxidizing alcohols in a liquid phase by a reaction agent composed of sulfite, hydrogen sulfite, thiosulfate or pyrosulfite, and a reducing inorganic compound as an activator to halogen acid or its salt Then, a method for promoting the oxidation of alcohols is included. In the present specification, not only compounds having a hydroxyl group as a primary alcohol group or a secondary alcohol group (for example, monohydric alcohols, diols and polyols), but also alcohols, acetals and alcohols having a hydroxyl group converted to a lower alkoxy group, Derivatives such as hemiacetal are also collectively referred to as "alcohols". Unless otherwise specified, halogen acids or salts thereof may be collectively referred to as “halogen acids”.

[0014]

BEST MODE FOR CARRYING OUT THE INVENTION The halogen acid or a salt thereof used in the present invention is represented by the formula M (XO ₃ ) _n . (In the formula, M represents a hydrogen atom or a metal, X represents a halogen atom, and n represents 1 or a valence of the metal.) The kind of the metal represented by M is not particularly limited as long as the activity of the halogen acid is not impaired. Without limitation, for example, alkali metals such as Na, K, Li (group 1A metals in the periodic table), Mg, Ca, S
Alkaline earth metals such as r and Ba (group 2A metals in the periodic table), Group 3A metals such as Sc and Y, Group 4A metals such as Ti and Zr, Group 5A metals such as V and Nb, Periodic Table 6A group metals such as Cr, Mo, W, Mn, T
Periodic Table 7A metals such as c, Fe, Ru, Co, Rh,
Transition metals such as Ni, Pd, Pt (group 8 metal of the periodic table),
Periodic table group 1B metals such as Cu, Ag, Au, Zn, Cd
Periodic Table 2B metal, Al, Ga, etc. Periodic Table 3B
Periodic Table 4B group metals such as Sn, Pb, Sb, B
The periodic table group 5B metals such as i are included. The preferred metal M often forms a water-soluble halogenate.

Preferred M includes a hydrogen atom or a trivalent metal such as an alkali metal (sodium, potassium etc.), an alkaline earth metal (magnesium, calcium etc.), aluminum and the like. Considering economical efficiency and safety, the M is often an alkali metal such as sodium or potassium.

The halogen atom represented by X is fluorine,
Includes chlorine, bromine and iodine atoms. Preferred halogen atoms are chlorine, bromine and iodine atoms, especially bromine atoms. It is known that in the oxidation reaction using hypohalous acid, the oxidizing power decreases in the order of Cl>Br> I.
A compound in which is a bromine atom and an iodine atom exhibits high oxidation activity. n is 1 or the valence of the metal M, and is 1 to 3.
Often around.

Specific examples of preferable halogen acid or its salt include, for example, bromic acid, alkali metal bromate (sodium bromate NaBrO ₃ , potassium bromate KBr).
O ₃ , lithium bromate, etc.), alkaline earth metal bromates (magnesium bromate, calcium bromate, etc.), zinc bromate, aluminum bromate, chloric acid or iodic acid corresponding to these bromic acids or their salts. Alternatively, salts thereof (for example, sodium chlorate, sodium iodate, etc.) and the like can be mentioned. These halogen acids or salts thereof can be used alone or in combination of two or more kinds. Of these halogen acids or salts thereof, bromic acid, alkali metal bromate (sodium bromate NaBrO ₃ , potassium bromate KBrO ₃ , lithium bromate, etc.), chloric acid or alkali metal chlorate, iodic acid or iodine Acid alkali metal salts, especially bromate alkali metal salts are often used.

The halogen acids may be produced in the reaction system. For example, the alkali metal bromate may be produced by blowing bromine into an aqueous solution containing the corresponding alkali metal hydroxide. The halogen acids are
It can be used as a solid such as crystals, an aqueous solution, or an appropriate organic solvent solution, and is often used as an aqueous solution.

A feature of the present invention is that the halogen acids are combined with a reducing inorganic compound. Oxidation reagent (reaction system) composed of such a combination
Has a high ability to oxidize alcohols as well as a high ability to selectively oxidize. In particular, the addition of the reducing inorganic compound greatly accelerates the oxidation reaction. Therefore, the reducing inorganic compound seems to function as an activator of halogen acids.

The reducing inorganic compound includes various inorganic compounds such as alkali metals (sodium, potassium,
Lithium, etc.), alkaline earth metals (magnesium, calcium, etc.), aluminum, chromium, manganese, transition metals (iron, nickel, etc.), simple metals such as copper and zinc, or salts of these metals or ammonia with inorganic acids. (For example, sulfate, sulfite, hydrogen sulfite, thiosulfate, pyrosulfite, nitrate, hydrochloride, phosphate, carbonate, etc.) are included. Of these inorganic compounds,
Alkali metals, alkali metal salts and ammonium salts are extremely useful in enhancing the activity of halogen acids. Alkaline earth metals (magnesium, calcium, etc.), aluminum, chromium, manganese, or salts thereof have a relatively high reaction activity as compared with transition metals (iron, nickel, etc.), copper, zinc or salts thereof. Show.

Preferred reducing inorganic compounds include alkali metal salts or ammonium salts as described above, particularly metal sulfites (eg sodium sulfite Na ₂ SO ₃ , potassium sulfite alkali metal sulfite, ammonium sulfite, etc.), Hydrogen sulfite metal salt (for example, sodium hydrogen sulfite NaHSO ₃ , alkali metal hydrogen sulfite such as potassium hydrogen sulfite, ammonium sulfite, etc.), thiosulfate metal salt (for example, sodium thiosulfate Na ₂ S ₂
O ₃ , alkali metal thiosulfate such as potassium thiosulfate, ammonium thiosulfate), pyrosulfite (alkali metal pyrosulfite such as sodium pyrosulfite, potassium pyrosulfite, ammonium pyrosulfite) and the like are included. These reducing inorganic compounds can be used alone or in combination of two or more. As the reducing compound, a metal sulfite, a metal hydrogen sulfite, a metal thiosulfate and the like are often used.

The amount of the reducing inorganic compound to be used can be selected within a range that does not impair the activity of the halogen acids and the selective oxidizing ability. For example, it is 0.1 to 5 per 1 equivalent of the halogen acids in terms of halogen acid. Equivalent, preferably 0.25 to 2.5
The amount is equivalent, more preferably about 0.5 to 1.5 equivalent. The reducing inorganic compound is often used in a ratio of 0.7 to 1.3 equivalents, particularly 0.9 to 1.1 equivalents per 1 equivalent of halogen acids.

Such an oxidation reaction agent (oxidation system) is useful for selectively producing a carbonyl compound from alcohols, and by selecting the kind or addition amount of halogen acid or reducing inorganic compound. It is highly versatile because it can selectively oxidize various alcohols. Therefore, in the method of the present invention, alcohols are oxidized using the oxidation reaction agent.

As alcohols, primary alcohols having a primary alcohol group and secondary alcohols having a secondary alcohol group can be used, and the alcohols may be monohydric or polyhydric alcohols. Among the alcohols, examples of monohydric alcohols include methyl alcohol, ethyl alcohol, propyl alcohol, isopropyl alcohol, butyl alcohol, isobutyl alcohol and s-.
Butyl alcohol, pentyl alcohol, 2-pentanol, isopentyl alcohol, neopentyl alcohol, hexyl alcohol, 2-hexanol, 3-hexanol, isohexyl alcohol, heptyl alcohol, 2-heptanol, octyl alcohol, 2-octanol, 2- Ethylhexyl alcohol, nonyl alcohol, decyl alcohol, allyl alcohol, crotyl alcohol, propargyl alcohol, geraniol, phytol and other linear or branched aliphatic alcohols having about 1 to 20 carbon atoms (saturated or unsaturated aliphatic alcohols ); Cyclopentanol, cyclohexanol, 2-methylcyclohexanol, 3-methylcyclohexanol, 4-methylcyclohexanol, 4-t
-Butyl cyclohexanol, cycloheptanol, cyclooctanol, etc., which may have a substituent (such as an alkyl group) and has an alicyclic alcohol having about 3 to 12 carbon atoms; benzyl alcohol, phenethyl alcohol, cinnamyl alcohol, salicyl Alcohol, 1,1-diphenylmethanol, 2-phenyl-2-ethanol,
Aromatic alcohols such as 1,1-diphenylethanol; heterocyclic alcohols such as furfuryl alcohol are included.

Examples of polyhydric alcohols are ethylene glycol, 1,2-propanediol, 1,3-propanediol, 1,2-butanediol, 1,3-butanediol, 1,4-butanediol, 2,3-butanediol, 1,2-pentanediol, 1,3-pentanediol, 2,3-pentanediol, 1,5-pentanediol, neopentyl glycol, 1,2-hexanediol, 1,3- Hexanediol, 1,4-hexanediol, 2,3-hexanediol, 2,4-
Hexanediol, 1,6-hexanediol, 1,8
-Octanediol, 1,2-octanediol, 1-
Phenyl-1,2-ethanediol, 1,2-diphenylethanediol, and other alkylene glycols that may have a substituent (for example, alkylene glycols having about 2 to 20 carbon atoms); diethylene glycol, triethylene glycol, etc. Number of repeating oxyethylene units 2
Approximately 20 to about 20 propylene units such as polyethylene glycol, dipropylene glycol, tripropylene glycol and the like, 2 to 20 polypropylene glycol and oxytetramethylene unit repeat numbers 2 to 2
Oxyalkylene glycols such as polytetramethylene glycol of about 0; aliphatic polyhydric alcohols having 3 or more hydroxyl groups such as glycerin, trimethylolpropane, trimethylolethane, and pentaerythritol; 1,2-cyclopentanediol, 1, 3-cyclopentanediol, 1,2-cyclohexanediol, 1,3-cyclohexanediol, 1,4-cyclohexanediol, 1,2-cycloheptanediol,
1,3-cycloheptanediol, 1,4-cycloheptanediol, 1,2-cyclooctanediol, 1,
3-cyclooctanediol, 1,4-cyclooctanediol, 1,5-cyclooctanediol, bis (4
-Hydroxycyclohexyl) methane, 1,1-bis (4-hydroxycyclohexyl) ethane, 2,2-bis (4-hydroxycyclohexyl) propane, menthol, borneol and other cyclic polyhydric alcohols; monosaccharides (eg threose, arabinose , Ribose, xylose, glucose, galactose, mannose, fructose, etc.), oligosaccharides containing 2 to 10 monosaccharide units (eg, disaccharides such as sucrose, maltose, lactose; trisaccharides such as raffinose), 11 or more. Sugars such as polysaccharides containing monosaccharide units (starch, soluble starch, etc.); pentaerythritol, erythritol,
Sugar alcohols such as arabit, xylit, sorbit, mannitol, and inosit; intramolecular dehydration condensates of sorbit (1,4-sorbitan, 3,6-sorbitan,
1,5-sorbitan, 1,4,3,6-sorbide, etc.), an intramolecular dehydration condensation product of a chain sugar alcohol such as mannitol intramolecular dehydration condensation product (mannitan, etc.);
And cholesterol, steroid compounds such as testosterol, and the like.

These alcohols are, for example, alcohols in which the hydroxyl group has been converted to a protective group capable of leaving (for example, a lower alkoxy group such as a C _1-2 alkoxy group), derivatives such as acetals and hemiacetals. Which may have an unsaturated bond such as a double bond, a halogen atom, an alkoxy group (for example, a C _1-6 lower alkoxy group), a carbonyl group, an acyl group (for example, C
_1-7 lower acyl group), carboxyl group, alkoxycarbonyl group (eg C _1-6 lower alkoxy-carbonyl group), amino group, alkylamino group (eg mono- or di-C _1-4 alkylamino group) Alcohols having functional groups such as

By utilizing the above-mentioned oxidation reaction, various corresponding carbonyl compounds can be selectively produced at a high conversion rate depending on the type of alcohols and the substitution site of the hydroxyl group. For example, the hydroxyl groups of the substrate diol can be selectively oxidized to yield the corresponding carbonyl compound in stoichiometric yield and high selectivity. Further, it is possible to selectively oxidize polyhydric alcohols, which have been difficult to achieve in the past, for example, natural compounds such as diols, glycerins, sugars and steroids at the hydroxyl group site. Especially,
In the oxidation of polyhydric alcohols having a primary hydroxyl group and a secondary hydroxyl group, the oxidation of the secondary hydroxyl group is preferentially promoted by controlling the addition amount of halogenic acids, and the hydroxyketone compound is highly selective. Can be generated preferentially. Further, as the amount of halogen acids is increased with respect to the polyhydric alcohol having a plurality of secondary hydroxyl groups, the plurality of hydroxyl groups can be sequentially converted into an oxo group. For example, when about 1 to 1.5 moles of halogen acids are used in terms of halogen acid or periodate for a diol having two secondary hydroxyl groups, one hydroxyl group can be converted to an oxo group, and By using about 2 to 2.5 moles of acids, both hydroxyl groups can be converted into oxo groups.

More specifically, for example, an ester represented by the following formula (2a) can be selectively produced from a primary alcohol represented by the following formula (1) by an oxidative esterification reaction. The corresponding carboxylic acid (2b) can be selectively produced from the primary alcohol (1).

[0029]

Embedded image (In the formula, R ¹ represents an alkyl group, an alkenyl group, an alkynyl group, a cycloalkyl group or an aralkyl group.) In the above formula, the alkyl group represented by R ¹ is a straight chain corresponding to the alcohols. Or a branched C _1-20 alkyl group (preferably a C _2-10 alkyl group), and examples of the alkenyl group include vinyl, 1-propenyl, 2-
C _2-10 alkenyl groups such as propenyl, isopropenyl, butenyl and pentenyl groups are included, and alkynyl groups include C _2-10 alkynyl groups such as ethynyl and propynyl groups. Examples of the cycloalkyl group represented by R ¹ include a C _3-20 cycloalkyl group (preferably a C _4-10 cycloalkyl group) such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl and cyclooctyl. The aralkyl group includes, for example, a C _6-12 aryl-C _1-4 alkyl group such as benzyl and phenethyl group.

The ester (2a) and the carboxylic acid (2
b) can be efficiently produced by adjusting the amounts of the halogen acid and the reducing inorganic compound with respect to the alcohol (1). For example, the ester (2a)
Is less than 2.5 equivalents (for example, 1 to 2.3 equivalents, preferably about 1 to 2 equivalents) of halogen acids to the hydroxyl group of the primary alcohol (1), and less than 2.5 equivalents of the reducing inorganic compound. (For example, 1 to 2.3 equivalents, preferably 1 to 2 equivalents) can be efficiently produced, and the carboxylic acid (2b) is halogenated with respect to the hydroxyl group of the primary alcohol (1). Acids 2.5
Equivalent or more (for example, 2.5 to 5 equivalents, preferably 2.7
˜4 equivalents), or 2.5 equivalents or more of a reducing inorganic compound (for example, 2.5 to 5 equivalents, preferably about 2.7 to 4 equivalents) can be used to efficiently produce the compound. The carboxylic acid (2b) can also be obtained in a high yield by reacting in the presence of an acid or under acidic conditions, particularly in a system in which the amount of the halogen acid and the reducing inorganic compound relative to the primary alcohol (1) is large. . As the acid, various protic acids (inorganic acid, organic carboxylic acid) can be used. Examples of the inorganic acid include hydrofluoric acid, hydrochloric acid, hydrobromic acid, hydrohalic acid such as hydroiodic acid, sulfuric acid, nitric acid and phosphoric acid. Organic carboxylic acids include, for example, saturated carboxylic acids such as formic acid, acetic acid, trichloroacetic acid, trifluoroacetic acid and propionic acid, unsaturated carboxylic acids such as acrylic acid and methacrylic acid, saturated carboxylic acids such as oxalic acid, malonic acid and succinic acid. It includes unsaturated dicarboxylic acids such as dicarboxylic acid and maleic acid, and oxycarboxylic acids such as glycolic acid, lactic acid, malic acid, tartaric acid, citric acid and the like. A water-soluble organic carboxylic acid is often used as the organic carboxylic acid. These acid components may be used alone or in combination of two or more, and the inorganic acid and the organic carboxylic acid may be used in combination.

The reaction system adjusted with the above-mentioned protonic acid may be acidic, and has a pH of 5 or less (for example, about 0.1 to 5), preferably pH 3 or less (for example, about 0.5 to 3). The amount of the protic acid used can be selected within a range that can accelerate the oxidation reaction, and is, for example, 0.1 to 5 equivalents, preferably 0.3 to 3 equivalents, and more preferably 0.5 equivalent to 1 equivalent of the halogen acids. It is often about 2.5 equivalents.

In the oxidation method of the present invention, the corresponding ketone (4) can be selectively produced from the secondary alcohol (3) as represented by the following reaction formula.

[0033]

Embedded image (In the formula, R ² and R ³ are the same or different and are an alkyl group, an alkenyl group, an alkynyl group, a cycloalkyl group,
It represents an aralkyl group, and R ² and R ³ may combine with each other to form a non-aromatic ring.) In this reaction, if an excessive amount of halogen acids or a reducing inorganic compound is used and an alicyclic alcohol is oxidized, , Α-halogenoketone production increases. Therefore, ketones and α-halogenoketones can be selectively synthesized from alcohols by controlling the amounts of halogen acids and reducing inorganic compounds used. For example, the halogen acid is 2.5 equivalents or less (for example, 1.
2 equivalents) and a reducing inorganic compound of 2.5 equivalents or less (for example, 1.2 equivalents) are used, a corresponding ketone is obtained in a high yield, and halogen acids are 3 equivalents or more (for example, about 1 equivalent).
If about 3 to 5 equivalents) and a reducing inorganic compound are used in 3 equivalents or more (for example, about 3 to 4 equivalents), α-halogenoketone can be obtained in a high yield.

Examples of the alkyl group, alkenyl group, alkynyl group, cycloalkyl group and aralkyl group represented by R ² and R ³ include the same groups as described in the section of R ¹ . The non-aromatic ring includes a ring corresponding to the cycloalkyl group, for example, a C _4-10 cycloalkane ring. In the ketone formation reaction, as the secondary alcohol, a monohydric or polyhydric aliphatic alcohol having a secondary hydroxyl group (for example, C _3-10 alcohol or C _3-10
In many cases, a diol) and an alicyclic alcohol (eg, an alicyclic alcohol having a C _4-10 cycloalkane ring) are used.

Further, as shown in the following reaction formula, the corresponding lactone (6a) or dicarboxylic acid (6b) can be produced from the diol (5) having a primary alcohol group.

[0036]

Embedded image (In the formula, R ⁴ represents a hydrogen atom or a methyl group, n represents an integer of 3 or more, and R ⁴ may be different depending on the number of repetitions n.) In this reaction formula, the type and amount of the oxidation reactant Depending on the above, when a diol of about n = 3 to 5 is oxidized, a corresponding lactone is easily generated, and n is 5 or more (particularly n is 6 or more, for example, n = 7 to 20, preferably n = 8). ~ 1
When a diol having a long carbon chain (about 6) is oxidized, a corresponding dicarboxylic acid is easily generated.

When an aromatic alcohol is used as a substrate, the corresponding aromatic aldehyde can be efficiently produced.

In the oxidation reaction, the amount of halogen acid used is, for example, 0.5 with respect to the hydroxyl group of the substrate alcohol.
To 5 mol, preferably 0.7 to 2.5 mol, more preferably 0.8 to 1.5 mol, and the amount of the reducing inorganic compound used is 0.5 to 2 mol with respect to the halogen acids. ,
It is preferably 0.7 to 1.7 mol, more preferably 0.1.
It is about 8 to 1.5 mol. The amount of the halogen acid and the reducing inorganic compound used is 0.9 to 3 mol, preferably 1 to 2.5, with respect to the hydroxyl group of the substrate alcohol.
In many cases, the amount is about mol (for example, 1.1 to 2.5 mol). If the amount of the halogen acid used is too small, the reaction efficiency will decrease, and if it is excessive, a compound in which the oxidation reaction has further proceeded or a halogenated compound is likely to be produced. If the amount of reducing inorganic compound added is too small, the reaction rate tends to decrease.

Usually, the oxidation reaction of alcohols is usually carried out in the liquid phase. Liquid-phase oxidation of alcohols is often carried out in a homogeneous system containing at least water, since halogen acids are usually water-soluble, and they are miscible or compatible with water and are organic solvents inert to the reaction. , For example, acetonitrile, formamide, dimethylformamide, dimethylsulfoxide, ketones (acetone etc.), ethers (dioxane, tetrahydrofuran etc.), lower carboxylic acids (eg formic acid, acetic acid etc.), tertiary alcohols (t
-Butanol) or mixed solvents thereof may be used. Further, an organic solvent immiscible with water, for example, hexane, cyclohexane, benzene, toluene,
Hydrocarbons such as xylene, ethers such as diethyl ether, ketones such as methyl ethyl ketone and methyl isobutyl ketone, esters such as methyl acetate and ethyl acetate, or a mixed solvent thereof are used to form an aqueous phase and an organic solvent phase. The reaction may be carried out in a phase system (heterogeneous system). When the reaction is performed in a two-phase system, a phase transfer catalyst (for example, a quaternary ammonium salt), a surfactant and the like may be used in combination in consideration of solubility of substrate alcohols. Furthermore, substrate alcohols can be used as a solvent.

In the oxidation reaction, the order of adding the substrate alcohols and the respective components is not particularly limited, and can be set appropriately from the viewpoint of operability and the like. From the viewpoint of reaction operability, it is advantageous to add the reducing inorganic compound to a mixed liquid containing a substrate alcohol and a halogen acid at a predetermined temperature.

When a reducing inorganic compound is added to the reaction system as an activator when oxidizing alcohols using halogen acids as an oxidant, the alcohols are stoichiometrically added even at room temperature and pressure. Moreover, it is possible to oxidize at a high selectivity and obtain the corresponding carbonyl compound in a high yield.
Therefore, the oxidation reaction proceeds smoothly even under relatively mild conditions. The reaction temperature is, for example, 0 ° C to 150 ° C.
(For example, 0 ° C to 100 ° C), preferably 10 to 70
C., more preferably about 20 to 50.degree. Also,
The reaction is atmospheric pressure or pressurization (for example, about 1 to 10 atm)
You can do it below. If the reaction temperature and / or the reaction pressure are high, the oxidation may proceed further, and low molecular weight carboxylic acids may be by-produced.

After the completion of the reaction, the target oxidation product can be easily separated and purified by a conventional separation and purification means such as distillation, concentration, solvent extraction, recrystallization and chromatography. When the product of the oxidation reaction is insoluble or sparingly soluble in water, depending on the solvent, after the reaction is completed,
Although phase separation and precipitates may be generated, in the oxidation method of the present invention, since the conversion rate and the selectivity are high, in most cases,
The target product can be obtained with high purity even by a simple extraction operation. Moreover, since unreacted products of halogen acids and reducing inorganic compounds and their decomposed products have extremely high water solubility, unreacted products and impurities can be easily removed by washing with water. Therefore, in the method of the present invention, after the reaction,
By combining a simple organic solvent extraction and water washing,
The desired product can be obtained in high yield and high purity. As described above, the method of the present invention can promote the reaction under mild conditions and is very safe as compared with the conventional method. In addition, the alcohols can be oxidized with high conversion and selectivity, and the post-treatment process including separation and purification can be extremely simplified, and the target product can be obtained in high yield by a simple operation. Therefore, it is possible to oxidize alcohols very industrially and economically.

[0043]

EFFECTS OF THE INVENTION Since the oxidation reaction agent of the present invention is a combination of halogen acids and a reducing inorganic compound, it can oxidize alcohols with high reactivity and selectivity. Also,
Even under mild conditions, substrate alcohols can be efficiently oxidized with a stoichiometrically high conversion rate and selectivity. Therefore, it can be applied to various substrate alcohols and is highly versatile. In the oxidation method of the present invention, since the above-mentioned oxidation reaction agent is used, alcohols can be easily and efficiently oxidized, and the target compound can be obtained in a high yield. Moreover, the target compound can be easily separated and purified, and the target compound can be obtained industrially and economically advantageously.

[0044]

EXAMPLES The present invention will be described below in more detail with reference to Examples, but the present invention is not limited to these Examples. Example 1 100 g (1 mol) of cyclohexanol, NaBrO ₃
To a mixture of 181 g (1.2 mol) of 400 ml of an aqueous solution and 400 ml of acetonitrile, at 25 ° C., NaHS
200 ml of an aqueous solution of 125 g (1.2 mol) of O ₃ was gradually added dropwise, and the mixture was stirred for 1 hour for reaction. The reaction mixture was extracted with diethyl ether, the extract was washed with water, dried and concentrated to give cyclohexanone at a conversion of 9%.
It was obtained at 9% and a selectivity of 100%.

Example 2 100 g (1 mol) of cyclohexanol, NaClO ₃
A mixed solution of 128 g (1.2 mol) of 400 ml of an aqueous solution and 400 ml of acetonitrile was heated to 40 ° C.
aHSO ₃ 125 g (1.2 mol) aqueous solution 200 ml
Was gradually added dropwise and stirred for 2 hours to cause reaction. The reaction mixture was extracted with diethyl ether, the extract was washed with water, dried and concentrated to give cyclohexanone at a conversion rate of 80% and a selectivity of 80%.

Example 3 100 g (1 mol) of cyclohexanol, NaBrO ₃
A mixture of 181 g (1.2 mol) of 400 ml of an aqueous solution and 400 ml of acetonitrile was heated to 40 ° C.
200 ml of an aqueous solution of 151 g (1.2 mol) of ₂ SO ₃ was slowly added dropwise and the reaction was carried out by stirring for 2 hours. The reaction solution was extracted with diethyl ether, washed with water, dried and concentrated to give cyclohexanone at a conversion of 8%.
It was obtained at 0% and a selectivity of 80%.

Example 4 100 g (1 mol) of cyclohexanol, NaBrO ₃
A mixture of 181 g (1.2 mol) of 400 ml of an aqueous solution and 400 ml of acetonitrile was heated to 40 ° C.
₂ S ₂ O ₃ 190 g (1.2 mol) aqueous solution 200 ml
Was gradually added dropwise and reacted for 2 hours with stirring. The reaction solution was extracted with diethyl ether, the extract was washed with water,
By drying and concentrating, cyclohexanone was obtained with a conversion of 70% and a selectivity of 80%.

Example 5 100 g (1 mol) of cyclohexanol, NaBrO ₃
A mixed solution of 211 g (1.4 mol) of 400 ml of an aqueous solution and 400 ml of acetonitrile was heated to 40 ° C.
200 ml of an aqueous solution of 222 g (1.4 mol) of ₂ S ₂ O ₃
Was gradually added dropwise and reacted for 2 hours with stirring. The reaction solution was extracted with diethyl ether, the extract was washed with water,
By drying and concentrating, cyclohexanone was obtained with a conversion of 95% and a selectivity of 100%.

Example 6 116 g (1 mol) of 1,2-cyclohexanediol,
400 m of an aqueous solution of 362 g (2.4 mol) of NaBrO ₃
1 and 400 ml of acetonitrile at 25 ° C
Then, an aqueous solution of 250 g (2.4 mol) of NaHSO ₃ 20
0 ml was gradually added dropwise and the reaction was carried out with stirring for 1 hour. The reaction solution was extracted with diethyl ether, the extract was washed with water, dried, and concentrated to obtain 1,2-cyclohexanedinone at a conversion rate of 99% and a selectivity of 100%.

Example 7 226 g (1 mol) of 2,2-bis (4-hydroxycyclohexyl) propane and 362 g (2.4 g) of NaBrO ₃
Mol) aqueous solution 400 ml and acetonitrile 400
250 ml of NaHSO ₃ at 25 ° C. in a ml mixture.
200 ml of an aqueous solution of (2.4 mol) was gradually added dropwise to 1
The reaction was allowed to stir for an hour. The reaction mixture is extracted with diethyl ether, washed with water, dried, and concentrated to give 2,2
-Bis (4-oxycyclohexyl) propane was obtained with a conversion of 99% and a selectivity of 100%.

Example 8 116 g (1 mol) of 1,2-cyclohexanediol,
An aqueous solution of 181 g (1.2 mol) of NaBrO ₃ 400 m
1 and 400 ml of acetonitrile at 25 ° C
Then, an aqueous solution of 125 g (1.2 mol) of NaHSO ₃ 20
0 ml was gradually added dropwise and the reaction was carried out with stirring for 1 hour. The reaction solution was extracted with diethyl ether, washed with water, dried, and concentrated to obtain α-hydroxycyclohexanone with a conversion rate of 99% and a selectivity of 100%.

Example 9 76 g (1 mol) of 1,2-propanediol, NaBr
To a mixed solution of 400 ml of an aqueous solution of 181 g (1.2 mol) of O ₃ and 400 ml of acetonitrile, at 25 ° C., Na
200 ml of an aqueous solution of 125 g (1.2 mol) of HSO ₃ was gradually added dropwise and the reaction was carried out with stirring for 1 hour. The reaction solution was extracted with diethyl ether, washed with water, dried, and concentrated to obtain a ketal compound obtained by adding 1,2-propanediol to hydroxyacetone at a conversion rate of 99% and a selectivity of 100%. .

Example 10 A reaction was conducted in the same manner as in Example 1 except that the substrate alcohols shown in the table below were used in place of cyclohexanol.
The compounds shown in the table below were obtained. The amount of substrate alcohol used was 5 mmol, and NaBrO ₃ was used as 3 ml of a 6 mmol aqueous solution.
In a mixed solution of 10 ml of an aqueous solution of BrO ₃ and acetonitrile, at 25 ° C., 6 mM of an aqueous solution of 6 mmol of NaHSO ₃ was added.
1 was gradually added dropwise and reacted by stirring for the time shown in the table.

[0054]

[Table 1] As is apparent from Table 1, the corresponding ketone is obtained in high yield from the secondary alcohol.

Example 11 Substrate alcohols shown in the table below were used in place of 2,2-bis (4-hydroxycyclohexyl) propane, and NaBrO 2 was used.
_{When the} reaction was performed in the same manner as in Example 7 except that the ratio of ₃ / NaHSO ₃ and the reaction time were changed, the compounds shown in the following table were obtained. The amount of substrate alcohol used was 5 mmol, the amount of acetonitrile used was 10 ml, and NaBrO ₃ and NaHSO ₃ were used as aqueous solutions. For the substrate 2,2-bis (4-hydroxycyclohexyl) propane, t-butanol was used as a solvent instead of ace and nitrile.

[0056]

[Table 2] As is clear from Table 2, hydroxyketones and diketones can be obtained in high yields in diols as well as secondary alcohols. Further, in 1,2-cyclooctanediol, the corresponding hydroxyketone was formed in the stage where the reaction time was short.

Example 12 100 g (1 mol) of cyclohexanol, NaBrO ₃
To a mixture of 400 ml of an aqueous solution of 382 g (2.4 mol) and 400 ml of acetonitrile, at 25 ° C., Na ₂ H
200 ml of an aqueous solution of 250 g (2.4 mol) of SO ₃ was gradually added dropwise and the reaction was carried out with stirring for 1 hour. The reaction solution was extracted with diethyl ether, the extract was washed with water, dried, and concentrated to obtain α-bromocyclohexanone with a conversion rate of 99% and a selectivity of 100%.

Example 13 A reaction was conducted in the same manner as in Example 12 except that 3 mol of NaBrO ₃ and 4 mol of Na ₂ HSO ₃ were reacted at room temperature (about 25 ° C.) for 24 hours, and α-bromocyclohexanone was found to be present. The conversion was 74% and the selectivity was 100%.

Example 14 116 g (1 mol) of 1,2-cyclohexanediol,
NaBrO ₃ aqueous solution 600m of 563g (3.6 mol)
1 and 200 ml of acetonitrile at 25 ° C
Then, 200 g of Na ₂ HSO ₃ 250 g (2.4 mol)
The aqueous solution was gradually added dropwise and the reaction was allowed to stir for 1 hour. The reaction mixture was extracted with diethyl ether, the extract was washed with water, dried and concentrated to give 6-bromo-1,2-cyclohexanedione at a conversion rate of 99% and a selectivity of 100%.

Comparative Example 1 100 g (1 mol) of cyclohexanol, NaBrO ₃
A mixed solution of 181 g (1.2 mol) of 400 ml of an aqueous solution and 400 ml of acetonitrile was stirred and reacted at 25 ° C. for 1 hour. When the reaction mixture was analyzed, 85% of unreacted cyclohexanol remained.

Comparative Example 2 116 g (1 mol) of 1,2-cyclohexanediol,
A mixed solution of 181 g (1.2 mol) of NaBrO ₃ in 400 ml of water and 400 ml of acetonitrile was stirred and reacted at 25 ° C. for 1 hour. When the reaction solution was analyzed, 85% of unreacted 1,2-cyclohexanediol remained.

Example 15 A mixed solution of 1 mol of a primary alcohol, 400 ml of an aqueous solution of 2 mol of NaBrO ₃ and 400 ml of acetonitrile was added at 25 ° C. to an aqueous solution of 2 mol of 2 Na ₂ HSO _3.
00 ml was gradually added dropwise and the reaction was allowed to stir for 2 hours. The reaction solution was extracted with diethyl ether, the extract was washed with water,
Dried and concentrated to give the ester in the table below.

[0063]

[Table 3] When the reaction was performed in the same manner as above except that benzyl alcohol was used as the substrate alcohol, benzaldehyde was obtained in a yield of 51% and benzoic acid was obtained in a yield of 17%.

Example 16 A reaction was conducted in the same manner as in Example 15 except that NaBrO ₃ , Na ₂ HSO ₃ , acetonitrile and water were used in the proportions shown in the table, and 5 mmol of 1-octanol was reacted with stirring at room temperature for 2 hours. As a result, the ester or carboxylic acid shown in the table below was obtained. In addition, No. In 2, 2M-
The liquid property of the reaction system was adjusted to pH 1 with sulfuric acid and reacted. In addition, No. In 5, 10 mmol of 1-octanol as a substrate was used.

[0065]

[Table 4] Example 17 1,1-Dimethoxyoctane 10 mmol, NaBrO
_When 312 mmol, Na ₂ HSO ₃ 12 mmol, and 8 ml of water were used and the reaction was conducted in the same manner as in Example 15, 1-methoxy-1-octanone was obtained with a yield of 54%.

Example 18 1,1-dimethoxyoctane 5 mmol, n-butanol 5 mmol, NaBrO ₃ 12 mmol, Na ₂ H
Except using 12 mmol of SO ₃ and 8 ml of water,
When reacted in the same manner as in Example 15, butoxycarbonylheptane was obtained in a yield of 61% and 1-methoxy-1-octanone was obtained in a yield of 25%.

Example 19 1 mol of 1,4-butanediol and 382 g of NaBrO ₃
A mixture of 400 ml of an aqueous solution of (2.4 mol) and 400 ml of acetonitrile was added at 25 ° C. to Na ₂ HSO ₃ 2
200 g of an aqueous solution of 50 g (2.4 mol) was gradually added dropwise and the reaction was carried out with stirring for 2 hours. The reaction solution is extracted with diethyl ether, the extract is washed with water, dried and concentrated,
γ-Butyrolactone was obtained with a conversion of 60% and a selectivity of 100%.

Example 20 A reaction was conducted in the same manner as in Example 19 except that 1,5-pentanediol was used instead of 1,4-butanediol, and δ-valerolactone had a conversion rate of 60% and a selectivity. Obtained at 100%.

Example 21 5 mmol of 1,4-butanediol, NaBrO ₃ 1
When stirring reaction was carried out at 25 ° C. for 2 hours in the same manner as in Example 19 except that 5 mmol, Na ₂ HSO ₃ 15 mmol, acetonitrile 10 ml and water 20 ml were used, γ-butyrolactone was obtained in a yield of 62%. .

Example 22 1 mol of 1,6-hexanediol, NaBrO ₃ 382
g (2.4 mol) in 400 ml of an aqueous solution and 400 ml of acetonitrile were added to a mixture of Na ₂ HSO ₃ at 25 ° C.
200 ml of an aqueous solution of 250 g (2.4 mol) was gradually added dropwise and the reaction was allowed to stir for 2 hours. The reaction solution was extracted with diethyl ether, washed with water, dried, and concentrated to obtain adipic acid with a conversion rate of 71% and a selectivity of 100%.

Example 23 The reaction was performed in the same manner as in Example 22 except that 1,5-pentanediol was used instead of 1,6-hexanediol, and glutaric acid was obtained in a yield of 68%.

Example 24 The reaction was performed in the same manner as in Example 22 except that 1,10-decanediol was used instead of 1,6-hexanediol, and sebacic acid was obtained in a yield of 91%.

─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. ⁶ Identification code Internal reference number FI Technical indication C07C 47/54 C07C 47/54 49/04 9049-4H 49/04 A 49/385 9049-4H 49 / 385 A 49/76 9049-4H 49/76 A 51/235 2115-4H 51/235 53/126 2115-4H 53/126 55/14 2115-4H 55/14 61/00 2115-4H 61/00 63 / 00 2115-4H 63/00 Z 67/40 67/40 69/02 69/02 69/75 69/75 D C07D 307/33 C07D 307/32 EF

Claims (12)

[Claims] 1. A halogen acid represented by the following formula M (XO ₃ ) _n (wherein M is a hydrogen atom or a metal, X is a halogen atom, and n is 1 or the valence of the metal M). Alternatively, an alcohol oxidation reaction agent composed of a salt thereof and a reducing inorganic compound. 2. A halogen acid or a salt thereof, wherein M is a hydrogen atom or a monovalent metal, X is a chlorine, bromine or iodine atom, and n is an integer of 1 to 3. Agent. 3. The alcohol oxidizing agent according to claim 1, wherein the halogen acid or a salt thereof is chloric acid, bromic acid, iodic acid or a salt thereof. 4. The alcohol oxidizing agent according to claim 1, wherein the reducing inorganic compound is a sulfite, a hydrogen sulfite, a thiosulfate or a pyrosulfite. 5. The alcohol oxidation reaction agent according to claim 1, wherein the ratio of the reducing inorganic compound to 1 equivalent of the halogen acid or its salt is 0.1 to 5 equivalents. 6. A method for oxidizing an alcohol, which comprises oxidizing a primary or secondary alcohol with the reactant according to claim 1. 7. The oxidation method according to claim 6, wherein the monohydric or polyhydric alcohol is oxidized in a liquid phase. 8. The following formula: (In the formula, R ¹ represents an alkyl group, an alkenyl group, an alkynyl group, a cycloalkyl group, an aryl group, or an aralkyl group). The oxidation method according to claim 6, wherein a carboxylic acid corresponding to an ester or a primary alcohol represented by the formula (wherein R ¹ is the same as above) is produced. 9. The oxidation method according to claim 6, wherein the corresponding ketone is produced from the secondary alcohol. 10. The oxidation method according to claim 6, wherein the corresponding lactone or dicarboxylic acid is produced from the diol. 11. A liquid phase is used to oxidize alcohols with a reactant composed of chloric acid, bromic acid, iodic acid or salts thereof and sulfite, hydrogen sulfite, thiosulfate or pyrosulfite. Oxidation method. 12. A method of promoting the oxidation of alcohols by adding a reducing inorganic compound as an activator to a halogen acid or a salt thereof.