JPH07188204A - Production of acetal lactone or acetal carboxylic acid - Google Patents

Abstract

PURPOSE:To safely and simply produce the subject compound in high efficiency by oxidizing a cyclic ketone having an alkoxy group on a carbon at alpha-position in the presence of a metal compound and an aldehyde using a safe and inexpensive oxygen as an oxidizing agent. CONSTITUTION:A cyclic ketone having an alkoxy group on a carbon at alphaposition is reacted with oxygen in the presence of a compound of a metal such as nickel or cobalt and an aldehyde compound to afford the objective acetal lactone. The acetal lactone is further treated with an alcohol in the presence of an acid catalyst to give the objective acetal carboxylic acid. As the cyclic ketone, a ketone compound of formula I (R<1> is an alkyl or a cycloalkyl; R<2> to R<7> each is H, a halogen, an alkyl, a cycloalkyl, an aryl, nitro, cyano, etc.) is preferably used. As the metal compound, a metal compound selected from complexes of nickel, cobalt, manganese, iron, copper and vanadium, respectively having 1,3-diketone compound as a ligand is preferably used. The compound of formula II and formula III (R<8> and R<9> each is an alkyl or a cycloalkyl) are obtained by this reaction.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a method for producing acetal lactone or acetal carboxylic acid, and in particular,
The present invention provides a simple method for producing acetal lactone or acetal carboxylic acid, which is a useful intermediate when synthesizing sugar, marine natural products, antibiotics and the like.

[0002]

As a method for obtaining acetal lactone, a cyclic α-alkoxy ketone is generally treated with peracetic acid and m
-Using a peroxide such as chloroperbenzoic acid, Baeyer-Billi
A method of producing by the ger reaction is known. However, these peroxides are sensitive to impact and have explosive properties, and thus require careful handling.

Further, conventionally, as a method for obtaining acetal carboxylic acids, (1) a cyclic olefin compound is oxidatively cleaved using ozone in the presence of a p-toluenesulfonic acid catalyst and an alcohol to obtain an acetal alkoxy hydroperoxide. Dehydration with acetic anhydride-triethylamine (Stuart L. Schreiber, Ronald E. Clau
s, and Jeff Reagan, Tetrahedron Lett., 23, 3867 (19
82)), (2) A method of reacting α-hydroxycyclohexanone with lead tetraacetate in methanol and then adding sulfuric acid to the reaction mixture (Charless D. Hurd and William.
H. Saunders, J. Am. Chem. Soc., 74,5324 (1952)) and the like are known to obtain an ester form of acetal carboxylic acid, and the resulting ester form is hydrolyzed to obtain an acetal carboxylic acid. The acid can be obtained.

[0004]

However, the above method (1) has an apparatus problem that an electrode device for applying a high voltage to generate ozone is required.
Further, ozone is very toxic to the human body, and further has a safety problem such as generation of hydroperoxide which has a risk of explosion as an intermediate of the reaction. Further, since the method (2) requires a stoichiometric amount of lead, which is a heavy metal, the treatment of waste liquid containing lead remaining after the reaction becomes a big problem.

Therefore, the object of the present invention is that it is not necessary to use peroxide, ozone, etc., and does not produce a reaction intermediate such as hydroperoxide which poses a safety problem during the reaction, and further, after the reaction is completed, It is an object of the present invention to provide a method capable of safely and simply producing acetal lactone or acetal carboxylic acid with high efficiency because treatment of waste liquid does not pose a problem.

[0006]

In order to solve the above problems, the present inventors can efficiently synthesize acetal lactone or acetal carboxylic acid using safe and inexpensive oxygen as an oxidizing agent. We have earnestly studied the method. As a result, we found that acetal lactone can be obtained in high yield by reacting a cyclic ketone compound having an alkoxy group at the α-position in the presence of a metal compound and an aldehyde compound in an oxygen atmosphere at room temperature and pressure. It was Furthermore, it was found that it is possible to easily convert the acetal lactone thus obtained to an acetal carboxylic acid by treating the reaction mixture with alcohol in the presence of an acid catalyst without purifying, and thus the present invention was reached. did.

That is, in order to solve the above problems, the present invention provides an acetal lactone which comprises a step of reacting a cyclic ketone having an alkoxy group at the α-position carbon with oxygen in the presence of a metal compound and an aldehyde compound. A manufacturing method is provided.

In the present invention, a cyclic ketone having an alkoxy group at the α-position carbon is reacted with oxygen in the presence of a metal compound and an aldehyde compound, and the resulting reaction mixture is treated with an alcohol in the presence of an acid catalyst. The present invention also provides a method for producing an acetal carboxylic acid having a step of treating with.

The method for producing the acetal lactone or acetal carboxylic acid of the present invention (hereinafter referred to as "the method of the present invention") will be described in detail below.

The cyclic ketone having an alkoxy group at the α-position carbon used as a starting material in the present invention is a cyclic ketone having an alkoxy group at the α-position carbon adjacent to a carbonyl carbon (hereinafter referred to as "cyclic α-alkoxyketone compound"). “)” Is not particularly limited and can be appropriately selected depending on the target acetal lactone or acetal carboxylic acid. In particular, the method of the present invention is suitable as a method for producing a corresponding acetal lactone or acetal carboxylic acid using a cyclic α-alkoxyketone compound represented by the following general formula (a) as a starting material.

[0011]

[Chemical 2]

In the general formula (a), R ¹ is a linear or branched alkyl group or cycloalkyl group, which may have a substituent. R ² , R ³ , R ⁴ , R
⁵ , R ⁶ and R ⁷ may be the same or different and each is a hydrogen atom, a halogen atom, a linear or branched alkyl group, a cycloalkyl group, an aryl group, a nitro group, a cyano group, an alkoxy group, an acyl group, It is an alkoxycarbonyl group, an amino group or a silyl group, and may combine with each other to form a ring or a double bond.

Typical examples of the linear or branched alkyl group represented by R ¹ in the general formula (a) are methyl group, ethyl group, n-propyl group, n-butyl group, sec-butyl group and tert-butyl group. Group, n-pentyl group, n-hexyl group and the like, and typical examples of the cycloalkyl group include cyclopentyl group, cyclohexyl group, cycloheptyl group and the like. R ² , R ³ , R ⁴ , R
Representative examples of the halogen atom of ⁵ , R ⁶ and R ⁷ include:
Fluorine, chlorine, bromine and the like can be mentioned, and typical examples of the linear or branched alkyl group include a methyl group, an ethyl group,
n-propyl group, n-butyl group, sec-butyl group, t
Examples thereof include an ert-butyl group, an n-pentyl group and an n-hexyl group, and typical examples of the cycloalkyl group include a cyclopentyl group, a cyclohexyl group and a cycloheptyl group. As a typical example of the aryl group,
Examples thereof include a phenyl group, a p-methoxyphenyl group, a p-chlorophenyl group and a p-fluorophenyl group. Typical examples of the alkoxycarbonyl group include an n-butoxycarbonyl group, an n-octylcarbonyl group and a benzyloxycarbonyl group. Is mentioned. A typical example of the amino group is a dimethylamino group, and a typical example of the silyl group is a tert-butyldimethylsilyl group, ter.
Examples thereof include t-butyldimethylsilyl group. Also, n
Is an integer of 1 to 10, preferably an integer of 1 to 4.

As a typical example of the cyclic α-alkoxyketone compound represented by the general formula (a), the following formula (a-1)
To (a-7) are included.

[0015]

[Chemical 3]

In the method of the present invention, the starting cyclic α
-When the cyclic α-alkoxyketone compound represented by the general formula (a) is used as the alkoxyketone compound, an acetal lactone or acetal carboxylic acid represented by the following general formula (b) or (c) can be obtained. it can.

[0017]

[Chemical 4]

In this general formula (b) or (c),
R ^{1 to} R ⁷ and n are as defined for the general formula (a). R ⁸ and / or R ⁹ is a linear or branched alkyl group or cycloalkyl group derived from an alcohol used as a nucleophile, and typical examples thereof include a methyl group, an ethyl group, an n-propyl group, n
-Butyl group, sec-butyl group, tert-butyl group,
n-pentyl group, n-hexyl group, cyclopentyl group,
Examples thereof include a cyclohexyl group and a cycloheptyl group.

As typical examples of the acetal lactone or acetal carboxylic acid represented by the general formula (b) or (c), the following formulas (b-1) to (b-3) or (c-
Examples thereof include those represented by 1) to (c-7).

[0020]

[Chemical 5]

The metal compound used in the method of the present invention is not particularly limited and, for example, a complex of at least one transition metal selected from nickel, iron, copper, manganese, cobalt and vanadium is representative. Can be mentioned. As a representative example of the complex of at least one transition metal selected from nickel, iron, copper, manganese, cobalt and vanadium, a complex compound represented by the following general formula (d) can be given.

[0022]

[Chemical 6]

In the general formula (d), R ^{10 to} R ¹² , R ¹³
To R ¹⁵ and R ^{16 to} R ¹⁸ may be the same or different and each is a hydrogen atom, an alkyl group, particularly an alkyl group having 1 to 10 carbon atoms, an aryl group or an alkoxy group, particularly 1 to 1 carbon atoms.
0 is an alkoxy group, a halogenated alkyl group, an alkoxycarbonyl group or an amino group. M is nickel, iron, copper, manganese, cobalt, or vanadium.

Typical examples of this metal compound include those represented by the following formulas (d-1) to (d-6).

[0025]

[Chemical 7]

In the method of the present invention, the metal compounds may be used alone or in combination of two or more.

In the method of the present invention, the amount of these metal compounds used is 0.001 to 50 mol based on the cyclic α-alkoxyketone compound, since acetal lactone or acetal carboxylic acid can be obtained in high yield. %, Preferably 0.1 to 10 mol%.

Further, in the method of the present invention, the aldehyde compound used together with the metal compound is not particularly limited and, for example, one represented by the following general formula (e) can be used.

[0029]

[Chemical 8]

In the general formula (e), R ¹⁹ is a linear or branched alkyl group, a cycloalkyl group or an aryl group, which may have a substituent. Typical examples of the linear or branched alkyl group include a methyl group, an ethyl group, an n-propyl group, an iso-propyl group,
n-butyl group, sec-butyl group, tert-butyl group, iso-butyl group, n-pentyl group, n-hexyl group, n-heptyl group, n-octyl group, n-nonyl group,
Examples thereof include n-decyl group, n-undecyl group and n-dodecyl group, and typical examples of the cycloalkyl group include cyclohexyl group, cyclopentyl group, cycloheptyl group, cyclooctyl group and the like. In addition, typical examples of the aryl group include a phenyl group and a p-methoxyphenyl group. Further, the linear or branched alkyl group, cycloalkyl group or aryl group may have a substituent, and may have a halogen atom such as fluorine or a methoxy group as a substituent. .

As typical examples of the aldehyde compound represented by the general formula (e), acetaldehyde, propionaldehyde, butyraldehyde, valeraldehyde, hexylaldehyde, heptylaldehyde, octylaldehyde, nonylaldehyde, decylaldehyde, undecylaldehyde, Dodecyl aldehyde, isobutyraldehyde, 2-methyl butyraldehyde, 2-ethyl butyraldehyde, 2-methyl valeraldehyde, isovaleraldehyde, pivalaldehyde, 2-phenylpropionaldehyde, 3-phenylpropanal, cyclohexanecarbaldehyde and the like. To be

The aldehyde compounds represented by the general formula (e) can be used alone or in combination of two or more.

In the method of the present invention, the above general formula (e)
The amount of the aldehyde compound used is usually 1 to 10 times mol, preferably 2 to 3 times mol, of the cyclic α-alkoxyketone compound represented by the general formula (a) which is a starting material. Is used.

In the method of the present invention, the above general formula (a)
As the oxygen used in oxidizing the cyclic α-alkoxyketone represented by, pure oxygen, air, or an oxygen-containing gas diluted with an inert gas can be used.
The reaction can be carried out under an oxygen partial pressure of 0.1 to 20 atm, preferably 0.2 to 10 atm.

In the method of the present invention, the reaction can be carried out by diluting with an organic solvent, and the organic solvent used is not particularly limited, and examples thereof include aliphatic hydrocarbon type, alicyclic hydrocarbon type and halogen. A hydrocarbon solvent, a ketone solvent, an ester solvent, a nitrile solvent, an amide solvent, or an aromatic hydrocarbon solvent can be used. Examples thereof include hexane, heptane, cyclohexane, dichloromethane, 1,2-dichloroethane, methyl ethyl ketone, methyl isobutyl ketone, ethyl acetate, acetonitrile, dimethylformamide, benzene and toluene.

The reaction temperature is appropriately selected depending on the starting cyclic α-alkoxyketone compound. Usually, it is preferably carried out in the range of 0 to 70 ° C. Also, the reaction time is appropriately determined depending on the cyclic α-alkoxyketone compound.

In addition, in the method of the present invention, following the production of the acetal lactone, the obtained acetal lactone is used as it is in the reaction mixture without isolation and purification.
Alternatively, the produced acetal lactone can be isolated once and then treated with alcohol as a nucleophile in the presence of an acid catalyst to cleave the acetal lactone to produce an acetal carboxylic acid.

The alcohol used for producing the acetal carboxylic acid in the present invention is not particularly limited, and for example, those represented by the following general formula (f) or (g) can be used.

[0039]

[Chemical 9]

In this general formula (f) or (g),
R²⁰Is a linear or branched alkyl group, R^{twenty one}~
R^{twenty two}May be the same or different, and may be a hydrogen atom or a straight chain.
Or branched alkyl group, or cycloalkyl group
Is. R²⁰, R^{twenty one}Or R ^{twenty two}Straight or branched
Typical examples of the alkyl group include methyl group, ethyl group, n
-Propyl group, iso-propyl group, n-butyl group, s
ec-butyl group, tert-butyl group, iso-butyl group
Group, n-pentyl group, n-hexyl group, n-heptyl
Group, n-octyl group, n-nonyl group, n-decyl group, n
-Undecyl group, n-dodecyl group and the like, and cyclo
Typical examples of the alkyl group include cyclohexyl group and cyclo
Ropentyl group, cycloheptyl group, cyclooctyl group, etc.
Is mentioned. n is an integer of 2 to 10, preferably 2 to 5
Is an integer.

Typical examples of the alcohol represented by the general formula (f) or (g) are methanol, ethanol,
Propanol, isopropanol, butanol, sec
-Butanol, tert-butanol, n-pentanol, n-hexanol, cyclohexanol, ethylene glycol, 1,3-propanediol, 1,2-propanediol, 1,4-butanediol and the like can be mentioned.

In the method of the present invention, the above general formula (f)
Alternatively, the amount of the alcohol represented by (g) is usually 1 to 1000 times mol of the cyclic α-alkoxyketone compound represented by the above-mentioned (a) which is a starting material.

The acid catalyst used in the production of the acetal carboxylic acid together with the alcohol represented by the general formula (f) or (g) is not particularly limited, and mineral acids such as hydrochloric acid, sulfuric acid and nitric acid, and Organic acids such as p-toluenesulfonic acid, trifluoromethanesulfonic acid, and trifluoroacetic acid can be used, and these acid catalysts can be used alone or in combination of two or more.

In the method of the present invention, the amount of these acid catalysts to be used is usually 0.0001 to 5 with respect to the cyclic α-alkoxyketone compound, since acetal carboxylic acid can be obtained in high yield. This is a double molar amount.

In producing the acetal carboxylic acid, the alcohol compound represented by the general formula (f) or (g) and the acid catalyst are added after the produced acetal lactone is once isolated and produced, or It can be added as it is to the reaction mixture containing acetal lactone after the oxidation reaction.

In the method of the present invention, when the produced acetal lactone is once isolated and produced and then converted into an acetal carboxylic acid, it can be diluted with an organic solvent. Examples of the organic solvent used include aliphatic hydrocarbons, alicyclic hydrocarbons, halogenated hydrocarbons, ketones, esters, nitriles, amides,
Aromatic hydrocarbon solvents can be used. Specific examples of this organic solvent include hexane, heptane, cyclohexane, dichloromethane, 1,2-dichloroloethane,
Methyl ethyl ketone, methyl isobutyl ketone, ethyl acetate, acetonitrile, dimethylformamide, benzene, toluene and the like can be mentioned.

The reaction temperature is appropriately selected depending on the acetal lactone. Usually, it is in the range of -50 to 50 ° C, preferably 0 to 25 ° C. Furthermore, the reaction time is appropriately selected depending on the acetal lactone.

In the method of the present invention, a cyclic α-alkoxyketone compound corresponding to the desired acetal lactone or acetal carboxylic acid, a metal compound, an aldehyde compound and, if necessary, a solvent are stirred under an oxygen atmosphere for reaction. It can be done by At this time, a cyclic α-alkoxyketone compound, a metal compound,
The mixing of the aldehyde compound and the solvent used as necessary can be carried out in a batch or by a flow method in which these are independently supplied.

[0049]

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

Example 1 1.0 mmol (12) of the cyclic α-alkoxyketone compound represented by the formula (a-1)
8 mg), a metal compound represented by the formula (d-1) 0.01
mmol (1 mol%), isovaleraldehyde 3 mm
ol (0.32 ml, 3 times mol relative to the cyclic α-alkoxyketone compound), and 1,2-dichloroethane 5
30 ml of the mixture at room temperature under a pure oxygen atmosphere at atmospheric pressure.
The reaction was allowed to stir for a minute. At this time, the reaction yield measured by gas chromatography was 100%. After the reaction was completed, 5 ml of a 1 mol / l diazomethane ether solution was added to the reaction mixture, and the mixture was stirred for 30 minutes to convert the carboxylic acid produced from isovaleraldehyde into a methyl ester, and the solvent was distilled off under reduced pressure. The obtained crude product was purified by silica gel column chromatography (eluent: hexane-ethyl acetate mixed solution) to obtain 104 mg of acetal lactone represented by the formula (b-1) (isolated yield 72%). .

(Examples 2 to 4) In each example, the formula (d-
4) to (d-6) were repeated except that the metal compounds represented by the formulas (b-6) were used to obtain the acetal lactone represented by the formula (b-1). The analysis of the reaction products was carried out by directly supplying the reaction mixture to the gas chromatograph at the time when the raw materials disappeared.
The results are shown in Table 1.

[0052]

[Table 1]

(Examples 5 and 6) In each example, the formula (a-
2) or (a-4), 1.0 mmol of the cyclic α-methoxyketone compound, 0.01 mmol (1 mol%) of the metal compound represented by the formula (d-1), 3 mmol of isovaleraldehyde (0. A mixture of 32 ml, 3 times the molar amount of the cyclic α-methoxyketone compound), and 5 ml of 1,2-dichloroethane was stirred and reacted at room temperature for 30 minutes under a pure oxygen atmosphere at atmospheric pressure. After the reaction,
5 ml of a 1 mol / l diazomethane ether solution was added to the reaction mixture, and the mixture was stirred for 30 minutes to convert the carboxylic acid produced from isovaleraldehyde into a methyl ester, and the solvent was distilled off under reduced pressure. The obtained crude product was purified by silica gel column chromatography (eluent: hexane-ethyl acetate mixed solution). The results are shown in Table 2.

[0054]

[Table 2]

(Examples 7 to 9) In each example, the formula (a-
1.0 m of cyclic α-methoxyketone compound represented by 1)
mol (128 mg), metal compounds represented by formulas (d-1) to (d-3) 0.01 mmol (1 mol%), isovaleraldehyde 3 mmol (0.32 ml, cyclic α)
-A mixture of 3 times mol of methoxyketone compound) and 5 ml of 1,2-dichloroethane were reacted under stirring at room temperature for 30 minutes under a pure oxygen atmosphere at atmospheric pressure. After completion of the reaction, methanol and 10% hydrochloric acid were added to the reaction mixture.
After adding 20 mg of a methanol solution and stirring for 3 hours, the solvent was distilled off under reduced pressure. The obtained crude product was purified by silica gel column chromatography (eluent: hexane-ethyl acetate mixed solution) to give an acetal carboxylic acid represented by the formula (c-1). The results are shown in Table 3.

[0056]

[Table 3]

(Examples 10 to 12) In each example, the reaction was carried out in the same manner as in Examples 7 to 9 except that propionaldehyde, isobutyraldehyde, or pivalaldehyde was used as the aldehyde compound. −
An acetal carboxylic acid represented by 1) was obtained. The reaction was carried out until the raw materials disappeared depending on the aldehyde compound.
The results are shown in Table 4.

[0058]

[Table 4]

(Examples 13 and 14) In each example, the reaction was carried out in the same manner as in Examples 7 to 9 except that 5 ml of ethanol or 124 mg of ethylene glycol was used as the alcohol during the alcohol treatment after the oxygen oxidation reaction. To obtain an acetal carboxylic acid represented by the formula (c-2) or (c-3). The results are shown in Table 5.

[0060]

[Table 5]

Examples 15 to 20 Same as Examples 7 to 9 except that cyclic α-alkoxyketone compounds represented by formulas (a-2) to (a-7) were used in each example. The reaction was carried out. The reaction time was appropriately determined according to the starting material. The results are shown in Table 6.

[0062]

[Table 6]

[0063]

EFFECTS OF THE INVENTION According to the method of the present invention, a cyclic ketone having an alkoxy group at the α-position carbon can be prepared under mild conditions,
Acetal lactone or acetal carboxylic acid can be produced in high yield. In particular, without using the conventionally required peroxides, ozone, etc., and since it does not produce reaction intermediates such as hydroperoxides in the course of the reaction, acetal lactone or acetal carboxylic acid can be safely and conveniently prepared. It can be manufactured with high efficiency.

 ─────────────────────────────────────────────────── ─── Continuation of the front page (72) Inventor Toru Yamada 580-32, Takuji Nagaura, Tsuboji Nagaura, Sodegaura City, Chiba Mitsui Petrochemical Industry Co., Ltd.

Claims (4)

[Claims] 1. A cyclic ketone having an alkoxy group at the α-position carbon is added in the presence of a metal compound and an aldehyde compound.
A method for producing acetal lactone, comprising the step of reacting with oxygen. 2. A cyclic ketone having an alkoxy group at the α-position carbon has the following general formula: [In the formula, R ¹ is a linear or branched alkyl group or a cycloalkyl group, which may have a substituent. R ² , R ³ , R ⁴ , R ⁵ , R ⁶ and R ⁷ may be the same or different and each is a hydrogen atom, a halogen atom, a linear or branched alkyl group, a cycloalkyl group, an aryl group or a nitro group. , A cyano group, an alkoxy group, an acyl group, an alkoxycarbonyl group, an amino group and a silyl group, and may be bonded to each other to form a ring or a double bond. ] The manufacturing method of the acetal lactone of Claim 1 which is a ketone compound represented by these. 3. The acetal according to claim 1, wherein the metal compound is at least one selected from nickel, cobalt, manganese, iron, copper and vanadium complexes having a 1,3-diketone compound as a ligand. Method for producing lactone. 4. A cyclic ketone having an alkoxy group at the α-position carbon is added in the presence of a metal compound and an aldehyde compound.
A method for producing an acetal carboxylic acid, which comprises a step of treating the obtained reaction mixture with alcohol in the presence of an acid catalyst after reacting with oxygen.