JP2003267915A - Method for producing 3,3-dimethyl-2- formylcyclopropanecarboxylic acid derivative - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a method for the industrial production of a 3,3-dimethyl-2- formylcyclopropanecarboxylic acid derivative expressed by general formula (2) (R is H, a (substituted)alkyl, a (substituted)aryl or a (substituted)aralkyl). <P>SOLUTION: The 3,3-dimethyl-2-formylcyclopropanecarboxylic acid derivative expressed by general formula (2) is produced by reacting a 3,3-dimethyl-2-(2- methyl-1-propenyl)cyclopropanecarboxylic acid derivative of general formula (1) (the definition of R is same as described above) with periodic acids in the presence of a ruthenium compound. <P>COPYRIGHT: (C)2003,JPO

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a method for producing a 3,3-dimethyl-2-formylcyclopropanecarboxylic acid derivative.

[0002]

2. Description of the Related Art General formula (1) (In the formula, R represents a hydrogen atom, an optionally substituted alkyl group, an optionally substituted aryl group or an optionally substituted aralkyl group.) 3,
3-Dimethyl-2- (2-methyl-1-propenyl) cyclopropanecarboxylic acid is a very important compound as a synthetic intermediate for pyrethroid-based household epidemic prevention agents, insecticides, etc. ) 3,3-dimethyl-2- (2-methyl-1-propenyl) cyclopropanecarboxylic acid as a key compound, the 2-methyl-1-propenyl group bonded to the cyclopropane ring to various alkenyl groups. A large number of substituted analogs and household epidemics and insecticides using the analogs have been developed.

As a method for producing an analog in which the 2-methyl-1-propenyl group bonded to the cyclopropane ring is substituted with various alkenyl groups, for example, the general formula (2) is used. (In the formula, R has the same meaning as described above.) A method of reacting a 3,3-dimethyl-2-formylcyclopropanecarboxylic acid derivative with a Wittig reagent (see Non-Patent Document 1, for example). The known 3,3-dimethyl-2-formylcyclopropanecarboxylic acid derivative represented by the above general formula (2) has become an important compound in the synthesis of the analog.

Conventionally, as a method for producing a 3,3-dimethyl-2-formylcyclopropanecarboxylic acid derivative represented by the general formula (2), for example, 3,3-dimethyl-2 represented by the above general formula (1). A method of oxidizing (2-methyl-1-propenyl) cyclopropanecarboxylic acid in the presence of an osmium tetroxide catalyst (see, for example, Non-Patent Document 1), 3,3-dimethyl represented by the above general formula (1). Method for ozone oxidation of 2- (2-methyl-1-propenyl) cyclopropanecarboxylic acid (for example, Patent Document 1)
reference. ) Etc. are known. However, the former method uses osmium tetroxide, which is highly toxic, and the latter method tends to require large-scale equipment.
Neither could be said to be an industrial manufacturing method.

[0005]

[Patent Document 1] Japanese Patent Publication No. 46-24695

[Non-Patent Document 1] J. Labeled Compou
nds and Radiopharmaceutic
als, 13 , 561 (1977)

[0006]

Under these circumstances, the inventor of the present invention has found that the 3,3-type compound represented by the above general formula (2) is used.
As a result of extensive studies on an industrial production method of a dimethyl-2-formylcyclopropanecarboxylic acid derivative, 3,3-dimethyl-2- (2-methyl) represented by the above general formula (1) was obtained in the presence of a ruthenium compound. By reacting -1-propenyl) cyclopropanecarboxylic acid with periodic acid, the desired 3,3-dimethyl-2-formylcyclopropanecarboxylic acid represented by the general formula (2) can be obtained in good yield. Finding that a derivative can be obtained,
The present invention has been completed.

[0007]

That is, the present invention provides a compound represented by the general formula (1) in the presence of a ruthenium compound. (In the formula, R represents a hydrogen atom, an optionally substituted alkyl group, an optionally substituted aryl group or an optionally substituted aralkyl group.) 3,
General formula (2) characterized by reacting 3-dimethyl-2- (2-methyl-1-propenyl) cyclopropanecarboxylic acid with periodic acid (In the formula, R represents the same meaning as described above.) A method for producing a 3,3-dimethyl-2-formylcyclopropanecarboxylic acid derivative represented by the above is provided.

[0008]

BEST MODE FOR CARRYING OUT THE INVENTION General Formula (1) 3,3-dimethyl-2- (2-methyl-1-) represented by
In the formula of propenyl) cyclopropanecarboxylic acid (hereinafter, abbreviated as carboxylic acid (1)), R is a hydrogen atom, an optionally substituted alkyl group, an optionally substituted aryl group or a substituted Represents an optional aralkyl group.

The alkyl group which may be substituted includes, for example, methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, sec-butyl group, tert-butyl group, n-pentyl group. Group, cyclopentyl group, n-hexyl group, cyclohexyl group, menthyl group and the like, straight chain, branched chain or cyclic alkyl group having 1 to 10 carbon atoms and these alkyl groups, for example, fluorine atom, chlorine atom, bromine Halogen atoms such as atoms, for example, methoxy group, ethoxy group, n-propoxy group, isopropoxy group, n-butoxy group, isobutoxy group, ter
An alkoxy group such as t-butoxy group, an aryloxy group such as a phenoxy group, a substituent such as an aralkyloxy group such as a benzyloxy group, and the like, for example, a 2-chloroethyl group, a 2-fluoroethyl group, and pentafluoroethyl. Group, 2-methoxyethyl group, 2-ethoxyethyl group, 2-phenoxyethyl group, 2- (benzyloxy)
Examples thereof include an ethyl group.

Examples of the aryl group which may be substituted include, for example, a phenyl group, a naphthyl group and the like, and an aromatic ring which constitutes these phenyl groups, naphthyl groups and the like, for example, the above-mentioned optionally substituted alkyl group and the above-mentioned alkoxy group. ,
Examples of the aryloxy group, the aralkyloxy group, and the like, which are substituted, include 2-chlorophenyl group, 4-fluorophenyl group, 2-methylphenyl group, 4-methoxyphenyl group, 4-phenoxyphenyl group, and the like. .

Examples of the optionally substituted aralkyl group include those comprising the above optionally substituted alkyl group and the above optionally substituted aryl group, for example, a benzyl group and a phenylethyl group. , Chlorobenzyl group, methylbenzyl group, methoxybenzyl group, phenoxybenzyl group, 2,3,5,6-tetrafluorobenzyl group, 2,3,5,6-tetrafluoro-4-methylbenzyl group, 2,3 , 5,6-Tetrafluoro-4
-Methoxybenzyl group, 2,3,5,6-tetrafluoro-4-methoxymethylbenzyl group and the like.

Examples of such carboxylic acids (1) include 3,3-dimethyl-2- (2-methyl-1-propenyl) cyclopropanecarboxylic acid and 3,3-dimethyl-2.
Methyl-(2-methyl-1-propenyl) cyclopropanecarboxylate, 3,3-dimethyl-2- (2-methyl-
1-propenyl) cyclopropanecarboxylate ethyl,
N-Propyl 3,3-dimethyl-2- (2-methyl-1-propenyl) cyclopropanecarboxylic acid, 3,3-
Dimethyl-2- (2-methyl-1-propenyl) cyclopropanecarboxylate isopropyl, 3,3-dimethyl-
N-Butyl 2- (2-methyl-1-propenyl) cyclopropanecarboxylate, isobutyl 3,3-dimethyl-2- (2-methyl-1-propenyl) cyclopropanecarboxylate, 3,3-dimethyl-2- Tert-butyl (2-methyl-1-propenyl) cyclopropanecarboxylate,

3,3-dimethyl-2- (2-methyl-1)
-Propenyl) phenyl phenylpropane propane,
3,3-dimethyl-2- (2-methyl-1-propenyl) cyclopropanecarboxylic acid (1-naphthyl), 3,
3-Dimethyl-2- (2-methyl-1-propenyl) cyclopropanecarboxylic acid (2-naphthyl), benzyl 3,3-dimethyl-2- (2-methyl-1-propenyl) cyclopropanecarboxylic acid, 3, 3-dimethyl-2-
(2-methyl-1-propenyl) cyclopropanecarboxylic acid (2,3,5,6-tetrafluorobenzyl),
3,3-Dimethyl-2- (2-methyl-1-propenyl) cyclopropanecarboxylic acid (2,3,5,6-tetrafluoro-4-methylbenzyl), 3,3-dimethyl-2- (2- Methyl-1-propenyl) cyclopropanecarboxylic acid (2,3,5,6-tetrafluoro-4-methoxybenzyl), 3,3-dimethyl-2- (2-methyl-1-propenyl) cyclopropanecarboxylic acid ( Two
3,5,6-tetrafluoro-4-methoxymethylbenzyl) and the like.

The carboxylic acid (1) has two asymmetric carbon atoms in its molecule and has four kinds of isomers. In the present invention, these isomers, either alone or in a mixture, are used. Either can be used.

Examples of the ruthenium compound include ruthenium metal, for example, ruthenium oxide such as ruthenium (IV) oxide, for example, ruthenium (III) chloride, ruthenium bromide (II).
Ruthenium halides such as I) such as tris (acetylacetonato) ruthenium (II), bis (cyclopentadienyl) ruthenium (II), bis (pentamethylcyclopentadienyl) ruthenium (II), dichloro (p- Cymen) ruthenium (II) dimer, dichloro (1,5-cyclooctadiene) ruthenium (II) dimer, benzene ruthenium (II) chloride dimer, tris (2,2′-bipyridyl) dichlororuthenium (II), dichlorotris ( Ruthenium complexes such as triphenylphosphine) ruthenium (II), carbonyldihydridotris (triphenylphosphine) ruthenium (II) and triruthenium dodecacarbonyl (0), for example, perruthenate (VII) tetra (n)
Examples include perruthenates such as -propyl) ammonium.

The ruthenium compound may be supported on activated carbon, silica, alumina or the like. A hydrate is usually used as the ruthenium oxide or the ruthenium halide.

The amount of the ruthenium compound used is usually 0.05 mol% or more, preferably 0.1 mol% or more, based on the carboxylic acid (1), and there is no particular upper limit, but if it is too large. Because it is easy to be economically disadvantageous,
Practically, it is 10 mol% or less, preferably 5 mol% or less.

As the periodate, its aqueous solution is acidic.
Periodic acids that exhibit
(H₅IO₆), Sodium metaperiodate (NaIO
_Four), Potassium metaperiodate (KIO_Four) Etc.
Be done. For example, lithium periodate (LiIO_Four), Para
Sodium periodate (Na_TwoH_ThreeIO₆, Na_ThreeH _Two
IO₆), Potassium dimesoperiodate (K_FourI_TwoO₉)
Periodic acid whose aqueous solution such as is neutral to alkaline
Are reacted in advance with an aqueous solution of acid such as sulfuric acid or nitric acid.
And convert the aqueous solution into periodic acid that exhibits acidity
Therefore, it can be used in the present invention. Also, that
Aqueous solution is neutral to alkaline
A mixture of boric acids (1) is prepared, for example, sulfuric acid, nitric acid, etc.
The reaction system is made acidic by adding an aqueous solution of acid.
In the reaction system, the aqueous solution generates periodic acid, which is acidic.
Alternatively, the reaction may be carried out.

Although there are hydrates among such periodic acids, anhydrate or hydrate may be used in the present invention.

The amount of periodate used is usually 2 mole times or more the amount of the carboxylic acid (1), and there is no particular upper limit. However, if it is too much, the target compound is more easily oxidized. Practically, it is 5 mol times or less, preferably 3 mol times or less with respect to the carboxylic acid (1).

The reaction between the carboxylic acid (1) and the periodic acid is usually carried out in a solvent. As the solvent, for example, toluene, xylene, mesitylene, an aromatic hydrocarbon solvent such as chlorobenzene, for example, pentane, hexane, heptane, octane, an aliphatic hydrocarbon solvent such as cyclohexane, for example, an ester solvent such as ethyl acetate, for example Methyl isobutyl ketone, ketone type solvents such as methyl ethyl ketone, for example, dichloromethane, dichloroethane, water-insoluble organic solvents such as halogenated aliphatic hydrocarbon type solvents such as carbon tetrachloride and water alone or a mixed solvent, preferably A mixed solvent of water and an organic solvent insoluble in water may be mentioned. The amount used is usually 2 times by weight or more, preferably 5 times by weight or more with respect to the carboxylic acid (1). There is no particular upper limit, but considering volumetric efficiency, etc.
Practically, the amount is 100 times or less the weight of the carboxylic acids (1). Further, when a mixed solvent of water and an organic solvent insoluble in water is used, the mixing ratio of water and the organic solvent insoluble in water is not particularly limited.

The reaction temperature is generally -10 to 50 ° C, preferably -5 to 15 ° C.

In this reaction, the carboxylic acid (1), the ruthenium compound and the periodic acid are usually mixed and brought into contact with each other, and the mixing order is not particularly limited.

After the completion of the reaction, if an insoluble matter is present in the reaction solution, for example, the insoluble matter is filtered off as it is to obtain the desired general formula (2). (In the formula, R represents the same meaning as described above.) An organic layer containing a 3,3-dimethyl-2-formylcyclopropanecarboxylic acid derivative (hereinafter abbreviated as carboxylic acid derivative (2)). Can be obtained. In addition, the reaction solution is heat-treated, and if necessary, water and / or an organic solvent insoluble in water is added to dissolve a part or all of the insoluble matter, followed by filtration treatment and / or liquid separation treatment. Thus, an organic layer containing the carboxylic acid derivative (2) can be obtained. When the reaction solution is heat-treated, the reaction solution may be heat-treated as it is, or from the viewpoint of suppressing the production of by-products due to the heat treatment, the heat treatment may be performed after adjusting the pH to around neutral. You can go.

When there is no insoluble matter in the reaction solution,
An organic layer containing the carboxylic acid derivative (2) can be obtained by adding water and / or a water-insoluble organic solvent to the obtained reaction liquid, if necessary, and subjecting the mixture to liquid separation.

The organic layer containing the obtained carboxylic acid derivative (2) is washed with, for example, an aqueous solution of sodium thiosulfate, if necessary, and then concentrated to remove the carboxylic acid derivative (2). . The carboxylic acid derivative (2) thus taken out may be further purified by a conventional purification means such as distillation or column chromatography.

When periodate remains in the reaction solution, inorganic reducing agents such as sodium sulfite, sodium thiosulfate, sodium hydrogen sulfite, etc., primary alcohols such as methanol, ethanol, etc. Alternatively, for example, secondary alcohols such as isopropyl alcohol and the like may be mixed, and the remaining periodate may be subjected to a reduction treatment, and then the above-mentioned treatment may be performed.

Further, depending on the ruthenium catalyst used,
The catalyst may be dissolved in the reaction solution, in which case, the reaction solution is mixed with an adsorbent such as activated carbon,
The catalyst may be removed by adsorption.

The filtered insoluble matter and the aqueous layer obtained by the liquid separation treatment produce iodic acids by-produced by the reaction between the carboxylic acids (1) and periodate (hereinafter abbreviated as by-produced iodic acids). It is preferable to convert by-product iodic acid to periodate and reuse it in the present invention because it is economical and reduces the iodine-containing waste, and therefore it is preferable from the viewpoint of environmental load. For example, when sodium metaperiodate (NaIO ₄ ) is used as the periodic acid, sodium iodate and / or iodic acid are by-produced as a by-product iodic acid.

As a method for converting by-produced iodic acids into periodate, for example, by-produced iodic acid and an oxidizing agent are reacted in the presence of an alkali, and the aqueous solution thereof is once converted into periodate, and then, For example, there may be mentioned a method in which an acid such as nitric acid or sulfuric acid is caused to act, and the aqueous solution thereof is converted into periodate which exhibits acidity.

Examples of the oxidizing agent include hypohalous acid salts such as sodium hypochlorite, halogens such as chlorine and bromine, and peroxodisulfate salts such as potassium peroxodisulfate. The amount is usually 1 to 3 times the molar amount of by-produced iodic acids. Examples of the alkali include alkali metal hydroxides such as sodium hydroxide and potassium hydroxide, and the amount thereof is usually 0.5 to 3 mole times the by-produced iodic acid. As the alkali, an aqueous solution is usually used.

The reaction temperature of the reaction between the by-produced iodic acid and the oxidizing agent is usually 50 to 100 ° C.

When the insoluble matter is reacted with the oxidizing agent, the reaction is usually carried out in water. The amount of water used is usually 2 to 10 times the weight of the insoluble matter. When the aqueous layer and the oxidant are reacted with each other, both of them may be directly contacted with each other and mixed, but water may be added if necessary.

Taking the case where the by-produced iodic acid is sodium iodate as a specific example, the by-product sodium iodate and an oxidizing agent such as sodium hypochlorite are mixed with each other in a water solvent, for example, with water. By reacting in the presence of an alkali such as sodium oxide, sodium paraperiodate, whose aqueous solution exhibits alkalinity, usually precipitates as crystals. Na _{2 for} sodium paraperiodate
There are two types, H ₃ IO ₆ and Na ₃ H ₂ IO ₆ ,
By appropriately selecting the reaction conditions such as the amount of alkali used and the pH of the reaction solution, Na ₂ H ₃ IO ₆ and Na ₃ H ₂ IO can be obtained.
_Since any one of ₆ can be selectively obtained, the reaction conditions may be selected according to the kind of the target sodium paraperiodate. Considering the amount of alkali used, the amount of acid used when converting to sodium metaperiodate, etc., it is economically advantageous and preferable to recover as Na ₂ H ₃ IO ₆ .

The precipitated sodium paraperiodate crystals are collected by filtration, washed as necessary, and then converted to sodium metaperiodate (NaIO ₄ ) by reacting with an acid such as nitric acid or sulfuric acid. The obtained sodium metaperiodate (NaIO ₄ ) may be isolated and reused in the reaction between the carboxylic acid (1) and the periodic acid, or without isolation, for example, acid The aqueous solution or suspension containing sodium metaperiodate (NaIO ₄ ) thus obtained may be reused as it is for the reaction between the carboxylic acids (1) and the periodic acid.

When the by-produced iodic acid is potassium iodate, the by-produced potassium iodate is reacted with an oxidizing agent such as chlorine in a water solvent in the presence of an alkali such as potassium hydroxide. , Potassium dimesoperiodate (K ₄ I ₂
After conversion into O ₉ ), an acid such as nitric acid is allowed to act on it to recover potassium metaperiodate (KIO ₄ ) as ordinary crystals.

Carboxylic acid derivative (2) thus obtained
As, for example, 3,3-dimethyl-2-formylcyclopropanecarboxylic acid, methyl 3,3-dimethyl-2-formylcyclopropanecarboxylic acid, ethyl 3,3-dimethyl-2-formylcyclopropanecarboxylic acid, 3,
N-Propyl 3-dimethyl-2-formylcyclopropanecarboxylate, isopropyl 3,3-dimethyl-2-formylcyclopropanecarboxylate, 3,3-dimethyl-
N-butyl 2-formylcyclopropanecarboxylate,
Isobutyl 3,3-dimethyl-2-formylcyclopropanecarboxylate, tert-butyl 3,3-dimethyl-2-formylcyclopropanecarboxylate,

Phenyl 3,3-dimethyl-2-formylcyclopropanecarboxylic acid, 3,3-dimethyl-2-formylcyclopropanecarboxylic acid (1-naphthyl),
3,3-Dimethyl-2-formylcyclopropanecarboxylic acid (2-naphthyl), benzyl 3,3-dimethyl-2-formylcyclopropanecarboxylic acid, 3,3-dimethyl-2-formylcyclopropanecarboxylic acid (2,3) Three
5,6-Tetrafluorobenzyl), 3,3-dimethyl-2-formylcyclopropanecarboxylic acid (2,3,3
5,6-tetrafluoro-4-methylbenzyl), 3,
3-dimethyl-2-formylcyclopropanecarboxylic acid (2,3,5,6-tetrafluoro-4-methoxybenzyl), 3,3-dimethyl-2-formylcyclopropanecarboxylic acid (2,3,5,6) -Tetrafluoro-4-
Methoxymethylbenzyl) and the like.

[0039]

The present invention will be described in more detail below with reference to examples, but the present invention is not limited to these examples. The analysis was performed by gas chromatography (internal standard method).

Example 1 Sodium paraperiodate (Na ₂ H ₃ IO ₆ ) 44.
To 4 g, add 195 g of water, and at an internal temperature of 25 ° C., 60% by weight
17.2 g of nitric acid was added, and sodium metaperiodate (N
An aqueous solution containing aIO ₄ ) was prepared. After 1.7 g of sodium metaperiodate (NaIO ₄ ) was newly added to the aqueous solution, the internal temperature was adjusted to 0 ° C. Ruthenium (III) chloride
Hydrate 32.6 mg, trans-3,3-dimethyl-2
Methyl-(2-methyl-1-propenyl) cyclopropanecarboxylate (14.2 g) and toluene (141 g) were added, and the mixture was stirred and reacted at the same temperature for 23.5 hours. After the reaction was completed, 2.2 g of isopropyl alcohol was added to reduce the remaining sodium metaperiodate (NaIO ₄ ), and then a 20 wt% sodium carbonate aqueous solution was added for neutralization treatment.

At an internal temperature of 70 ° C., 0.4 g of activated carbon was added, the mixture was stirred for about 30 minutes, and then filtered at the same temperature. After allowing the filtrate to stand,
Liquid separation treatment was performed to obtain an organic layer containing methyl trans-3,3-dimethyl-2-formylcyclopropanecarboxylate and an aqueous layer containing by-product sodium iodate and / or iodic acid. The organic layer was washed with an aqueous sodium thiosulfate solution and then concentrated under reduced pressure to give 26.9 g (content: 38.8) of a concentrated residue containing methyl trans-3,3-dimethyl-2-formylcyclopropanecarboxylate. Wt%) was obtained. Yield: 86%.

Further, 274 g of the aqueous layer was concentrated under reduced pressure to remove contained acetone and isopropyl alcohol, and then 26.9 g of a 30% by weight aqueous sodium hydroxide solution and 12.8% by weight of hypochlorous acid. A sodium acid aqueous solution (109.5 g) was added dropwise at an internal temperature of 80 ° C., and the mixture was stirred and reacted at the same temperature for 4 hours. Then, the internal temperature was cooled to 30 ° C. or lower, and 60 wt% nitric acid was added to adjust the pH to 6. The precipitated crystals were collected by filtration and dried under reduced pressure to give 46.1 g of sodium paraperiodate (Na ₂ H ₃ IO ₆ ). The recovery rate for the sodium paraperiodate and sodium metaperiodate used above was 99%.

Example 2 Sodium paraperiodate (Na ₂ H ₃ IO ₆ ) 26.
To 3 g, 58 g of water was added, 10.1 g of 60 wt% nitric acid was added at an internal temperature of 65 ° C., and sodium metaperiodate (Na
An aqueous solution containing IO ₄ ) was prepared. After adjusting the internal temperature to 0 ° C., 12.5 mg of ruthenium (IV) oxide hydrate, 8 g of methyl trans-3,3-dimethyl-2- (2-methyl-1-propenyl) cyclopropanecarboxylate and 80 g of toluene were added. In addition, the mixture was stirred and reacted at the same temperature for 23 hours.
After the reaction was completed, 1.8 g of isopropyl alcohol was added,
After the remaining sodium metaperiodate (NaIO ₄ ) was reduced, a 20 wt% sodium carbonate aqueous solution was added to neutralize the solution.

At an internal temperature of 0 ° C., the insoluble matter containing by-product sodium iodate was filtered off. The filtered insoluble matter was washed with toluene, and the washing solution was mixed with the previously obtained filtrate. The mixed filtrate was subjected to a liquid separation treatment, and the obtained organic layer was washed with an aqueous sodium thiosulfate solution to prepare trans-3,3-dimethyl-2-.
110.3 g (content: 5.5% by weight) of an organic layer containing methyl formylcyclopropanecarboxylate was obtained. Yield: 8
It was 8%.

Example 3 Sodium paraperiodate (Na ₂ H ₃ IO ₆ ) 26.
To 3 g, 58 g of water was added, 10.1 g of 60 wt% nitric acid was added at an internal temperature of 65 ° C., and sodium metaperiodate (Na
An aqueous solution containing IO ₄ ) was prepared. After adjusting the internal temperature to 0 ° C., 58.9 wt% ruthenium / alumina 178.9 mg, methyl trans-3,3-dimethyl-2- (2-methyl-1-propenyl) cyclopropanecarboxylate 8 g and toluene 80 g were added, The mixture was stirred and reacted at the same temperature for 28 hours. After the reaction was completed, 1.8 g of isopropyl alcohol was added, and the remaining sodium metaperiodate (NaI
After reducing O ₄ ), a 20 wt% sodium carbonate aqueous solution was added to carry out a neutralization treatment.

At an internal temperature of 0 ° C., the insoluble matter containing by-product sodium iodate was filtered off. The filtered insoluble matter was washed with toluene, and the washing solution was mixed with the previously obtained filtrate. The mixed filtrate was subjected to a liquid separation treatment, and the obtained organic layer was washed with an aqueous sodium thiosulfate solution to prepare trans-3,3-dimethyl-2-.
124.7 g (content: 4.9% by weight) of an organic layer containing methyl formylcyclopropanecarboxylate was obtained. Yield: 8
It was 9%.

Example 4 Sodium paraperiodate (Na ₂ H ₃ IO ₆ ) 13.
30 g of water was added to 5 g, and 5.3 g of 60 wt% nitric acid was added at an internal temperature of 65 ° C. to give sodium metaperiodate (NaI
An aqueous solution containing O ₄ ) was prepared. After adjusting the internal temperature to 0 ° C., 5 wt% ruthenium / activated carbon 91 mg, trans-
Methyl 3,3-dimethyl-2- (2-methyl-1-propenyl) cyclopropanecarboxylate (4.1 g) and toluene (41 g) were added, and the mixture was stirred and reacted at the same temperature for 21 hours. After the reaction was completed, 1.2 g of isopropyl alcohol was added, and the remaining sodium metaperiodate (NaIO ₄ ) was added.
Was reduced, and then a 20 wt% sodium carbonate aqueous solution was added for neutralization.

At an internal temperature of 0 ° C., the insoluble matter containing by-product sodium iodate was filtered off. The filtered insoluble matter was washed with toluene, and the washing solution was mixed with the previously obtained filtrate. The mixed filtrate was subjected to a liquid separation treatment, and the obtained organic layer was washed with an aqueous sodium thiosulfate solution to prepare trans-3,3-dimethyl-2-.
69.5 g (content: 4.4% by weight) of an organic layer containing methyl formylcyclopropanecarboxylate was obtained. Yield: 87
%Met.

Example 5 33 g of water was added to 10.8 g of sodium metaperiodate (NaIO ₄ ) to adjust the internal temperature to 0 ° C., and 10.4 mg of bis (cyclopentadienyl) ruthenium (II) was added. To this, 4.1 g of methyl trans-3,3-dimethyl-2- (2-methyl-1-propenyl) cyclopropanecarboxylate and 21 g of toluene were added, and the mixture was stirred and reacted at an internal temperature of 0 ° C. for 8 hours. After completion of the reaction, the insoluble matter containing by-product sodium iodate was filtered off, the filtered insoluble matter was washed with toluene, and the washing liquid was mixed with the previously obtained filtrate. The mixed filtrate was subjected to a liquid separation treatment, and the obtained organic layer was washed with an aqueous sodium thiosulfate solution to prepare trans-3,3-dimethyl-2-.
55.2 g (content: 5.9% by weight) of an organic layer containing methyl formylcyclopropanecarboxylate was obtained. Yield: 91
%.

Example 6 In Example 5, 10.4 mg of dichloro (p-cymene) ruthenium (II) dimer was used instead of 10.4 mg of bis (cyclopentadienyl) ruthenium (II), and the reaction time was 9 The same procedure as in Example 5 was carried out except that the time was changed to give 54.5 g (content: 5.4% by weight) of an organic layer containing methyl trans-3,3-dimethyl-2-formylcyclopropanecarboxylate. It was Yield: 83%.

Example 7 In Example 5, benzene ruthenium was used instead of 10.4 mg of bis (cyclopentadienyl) ruthenium (II).
(II) Using 5.5 mg of chloride dimer, the reaction time was 1
The same procedure as in Example 5 was carried out except that the time was set to 2 hours, and 54.7 g of an organic layer containing methyl trans-3,3-dimethyl-2-formylcyclopropanecarboxylate (content: 5.
3% by weight). Yield: 82%.

Example 8 Example 5 was repeated except that 42 mg of dichlorotris (triphenylphosphine) ruthenium (II) was used in place of 10.4 mg of bis (cyclopentadienyl) ruthenium (II) in Example 5. Perform the same procedure as in the transformer-3,
52.2 g of an organic layer containing methyl 3-dimethyl-2-formylcyclopropanecarboxylate (content: 5.6% by weight)
Got Yield: 82%.

Example 9 In Example 5, instead of 10.4 mg of bis (cyclopentadienyl) ruthenium (II), 18.1 mg of tris (acetylacetonato) ruthenium (III) was used, and the reaction time was 11 hours. 52.4 g of an organic layer containing methyl trans-3,3-dimethyl-2-formylcyclopropanecarboxylate was carried out in the same manner as in Example 5 except that
(Content: 5.7% by weight) was obtained. Yield: 85%.

Example 10 In Example 5, instead of 10.4 mg of bis (cyclopentadienyl) ruthenium (II), carbonyldihydridotris (triphenylphosphine) ruthenium (II) 4 was used.
The same procedure as in Example 5 was carried out except that 1.5 mg was used and the reaction time was 7 hours, and 58.9 g of an organic layer containing methyl trans-3,3-dimethyl-2-formylcyclopropanecarboxylate ( Content: 5.0% by weight) was obtained. Yield: 84%.

Example 11 In Example 5, instead of 10.4 mg of bis (cyclopentadienyl) ruthenium (II), perruthenate (VI) was used.
I) Trans-3,3-dimethyl-2-formylcyclopropanecarboxylic acid was carried out in the same manner as in Example 5 except that 15.4 mg of tetra (n-propyl) ammonium was used and the reaction time was 6 hours. Organic layer containing methyl 52.
6 g (content: 5.6% by weight) were obtained. Yield: 83%.

Example 12 16 g of water was added to 5.4 g of sodium metaperiodate (NaIO ₄ ) to adjust the internal temperature to 0 ° C., and ruthenium chloride (II
I) 11.4 mg of hydrate was added. To this, transformer
Methyl 3,3-dimethyl-2- (2-methyl-1-propenyl) cyclopropanecarboxylate (2 g) and dichloroethane (10 g) were added, and the mixture was stirred and reacted at an internal temperature of 0 ° C. for 4 hours. After completion of the reaction, the insoluble matter containing by-product sodium iodate was filtered off, the filtered insoluble matter was washed with dichloroethane, and the washing liquid was mixed with the previously obtained filtrate. The mixed filtrate was subjected to liquid separation treatment, the obtained organic layer was washed with an aqueous sodium thiosulfate solution, and an organic layer containing methyl trans-3,3-dimethyl-2-formylcyclopropanecarboxylate 26.
8 g (content: 5.4% by weight) were obtained. Yield: 85%.

Example 13 In Example 12, except that the same weight of hexane was used instead of dichloroethane and the reaction time was 10 hours.
The same procedure as in Example 12 was performed to obtain 36.4 g (content: 3.2% by weight) of an organic layer containing methyl trans-3,3-dimethyl-2-formylcyclopropanecarboxylate.
Yield: 68%.

Example 14 Trans-3,3-dimethyl-2-formylcyclopropane was prepared in the same manner as in Example 12 except that the same weight of ethyl acetate was used instead of dichloroethane. Organic layer containing methyl carboxylate 37.0 g
(Content: 3.5% by weight) was obtained. Yield: 76%.

Example 15 The procedure of Example 12 was repeated except that dichloroethane was replaced with the same weight of methyl isobutyl ketone and the reaction time was changed to 7 hours.
40.5 g (content: 3.3% by weight) of an organic layer containing methyl 3,3-dimethyl-2-formylcyclopropanecarboxylate was obtained. Yield: 79%.

Example 16 To 11.5 g of periodic acid (H ₅ IO ₆ ) was added 33 g of water, the internal temperature was adjusted to 0 ° C., and ruthenium (IV) oxide hydrate was added.
1 mg was added. To this, 4.1 g of methyl trans-3,3-dimethyl-2- (2-methyl-1-propenyl) cyclopropanecarboxylate and 41 g of toluene were added, and the mixture was stirred and reacted at an internal temperature of 0 ° C for 12 hours. The reaction solution was subjected to a liquid separation treatment, the obtained organic layer was washed with an aqueous sodium thiosulfate solution, and an organic layer containing methyl trans-3,3-dimethyl-2-formylcyclopropanecarboxylate 70.1
g (content: 4.6% by weight) were obtained. Yield: 91%.

Example 17 11.6 g of potassium metaperiodate (KIO ₄ ) and 3 parts of water
3 g was added, the internal temperature was adjusted to 0 ° C., and 6 mg of ruthenium (IV) oxide hydrate was added. To this, 4.1 g of methyl trans-3,3-dimethyl-2- (2-methyl-1-propenyl) cyclopropanecarboxylate and 20 g of toluene were added, and the mixture was stirred and reacted at an internal temperature of 0 ° C. for 24 hours. After completion of the reaction, the insoluble matter containing by-product potassium iodate was filtered off, the filtered insoluble matter was washed with toluene, and the washing solution was mixed with the previously obtained filtrate. The mixed filtrate was subjected to a liquid separation treatment, and the obtained organic layer was washed with an aqueous solution of sodium thiosulfate and trans-treated.
59.3 g (content: 3.1% by weight) of an organic layer containing methyl 3,3-dimethyl-2-formylcyclopropanecarboxylate was obtained. Yield: 52%.

[0062] Example 18 periodate lithium hydrate _{(LiIO 4 · 2H 2 O)} 1
35 g of water was added to 1.8 g to adjust the internal temperature to 0 ° C., and 6 mg of ruthenium (IV) oxide hydrate was added. To this, 4.1 g of methyl trans-3,3-dimethyl-2- (2-methyl-1-propenyl) cyclopropanecarboxylate, 41 g of toluene and 9 g of 60% by weight nitric acid were added, and the mixture was stirred at an internal temperature of 0 ° C. for 30 hours. , Reacted. After completion of the reaction, the insoluble matter containing by-product lithium iodate was filtered off, the filtered insoluble matter was washed with toluene, and the washing liquid was mixed with the previously obtained filtrate. The mixed filtrate was subjected to a liquid separation treatment, and the obtained organic layer was washed with an aqueous solution of sodium thiosulfate to obtain trans-3,3-dimethyl-
78.5 g (content: 3.4% by weight) of an organic layer containing methyl 2-formylcyclopropanecarboxylate was obtained. yield:
76%.

Example 19 33 g of water was added to 10.8 g of sodium metaperiodate (NaIO ₄ ) to adjust the internal temperature to 0 ° C., and ruthenium oxide (I
V) 6 mg of hydrate was added. To this, transformer-3,3-
Dimethyl-2- (2-methyl-1-propenyl) cyclopropanecarboxylic acid 4.1 g and toluene 21 g were added, and the mixture was stirred and reacted at an internal temperature of 0 ° C. for 23 hours. After completion of the reaction, the insoluble matter containing by-product sodium iodate was filtered off, the filtered insoluble matter was washed with toluene, and the washing liquid was mixed with the previously obtained filtrate. The mixed filtrate was subjected to liquid separation treatment, and the obtained organic layer was washed with an aqueous sodium thiosulfate solution to give 56.7 g of an organic layer containing trans-3,3-dimethyl-2-formylcyclopropanecarboxylic acid (content: 2.0% by weight) was obtained. Yield: 35%.

Example 20 33 g of water was added to 10.8 g of sodium metaperiodate (NaIO ₄ ) to adjust the internal temperature to 0 ° C., and ruthenium chloride (I
II) 9.1 mg of hydrate was added. To this, transformer
Methyl 3,3-dimethyl-2- (2-methyl-1-propenyl) cyclopropanecarboxylate (4.1 g) and toluene (41 g) were added, and the mixture was stirred and reacted at an internal temperature of 0 ° C. for 18 hours. After completion of the reaction, the insoluble matter containing by-product sodium iodate was filtered off, the filtered insoluble matter was washed with toluene, and the washing liquid was mixed with the previously obtained filtrate. The filtrate after mixing was subjected to a liquid separation treatment, the obtained organic layer was washed with an aqueous sodium thiosulfate solution, and 57.7 g of an organic layer containing methyl trans-3,3-dimethyl-2-formylcyclopropanecarboxylate (content: 5.6% by weight). Yield: 91%.

Example 21 33 g of water was added to 10.8 g of sodium metaperiodate (NaIO ₄ ) to adjust the internal temperature to 0 ° C., and ruthenium oxide (I
V) 6 mg of hydrate was added. To this, transformer-3,3-
4.1 g of methyl dimethyl-2- (2-methyl-1-propenyl) cyclopropanecarboxylate and toluene 41
g was added, and the mixture was stirred and reacted at an internal temperature of 0 ° C. for 12 hours. After completion of the reaction, the insoluble matter containing by-product sodium iodate was filtered off, the filtered insoluble matter was washed with toluene, and the washing liquid was mixed with the previously obtained filtrate. The mixed filtrate was subjected to a liquid separation treatment, the obtained organic layer was washed with an aqueous sodium thiosulfate solution, and 70.5 g of an organic layer containing methyl trans-3,3-dimethyl-2-formylcyclopropanecarboxylate (content: 4.
6% by weight) was obtained. Yield: 92%.

Example 22 Sodium paraperiodate (Na ₂ recovered in Example 1)
To 34.4 g of H ₃ IO ₆ ) was added 203 g of water, and the internal temperature was 0.
At 70 ° C., 17.2 g of 60% by weight nitric acid was added to prepare an aqueous solution containing sodium metaperiodate (NaIO ₄ ).
At the same temperature, 32.4 mg of ruthenium (III) chloride hydrate,
Trans-3,3-dimethyl-2- (2-methyl-1-
Methyl propenyl) cyclopropanecarboxylate 14.2
g and toluene (144 g) are added, and sodium metaperiodate (NaIO ₄ ) (1.7 g) is added, and then 2
The mixture was stirred and reacted for 5.5 hours. After the reaction was completed, 2.4 g of isopropyl alcohol was added to reduce the remaining sodium metaperiodate (NaIO ₄ ), and then a 20 wt% sodium carbonate aqueous solution was added for neutralization treatment.

At an internal temperature of 70 ° C., 0.2 g of activated carbon was added, the mixture was stirred for about 30 minutes, and then filtered at the same temperature. After allowing the filtrate to stand,
Liquid separation treatment was performed to obtain an organic layer containing methyl trans-3,3-dimethyl-2-formylcyclopropanecarboxylate and an aqueous layer containing by-product sodium iodate and / or iodic acid. The organic layer was washed with an aqueous sodium thiosulfate solution and then concentrated under reduced pressure to give a concentrated residue containing methyl trans-3,3-dimethyl-2-formylcyclopropanecarboxylate (27.5 g, content: 38.5). Wt%) was obtained. Yield: 87%

[0068]

According to the present invention, a 3,3-dimethyl-2-formylcyclopropanecarboxylic acid derivative can be industrially advantageously used without using highly toxic osmium tetroxide or ozone which tends to be bulky in equipment. It can be manufactured. Further, since the iodic acid by-produced in the reaction can be recovered as periodic acid and the recovered periodic acid can be reused in the present invention, it is an advantageous production method from the viewpoint of economical efficiency and environmental load.

Claims (6)

[Claims] 1. A compound represented by the general formula (1) in the presence of a ruthenium compound: (In the formula, R represents a hydrogen atom, an optionally substituted alkyl group, an optionally substituted aryl group or an optionally substituted aralkyl group.) 3,
General formula (2) characterized by reacting 3-dimethyl-2- (2-methyl-1-propenyl) cyclopropanecarboxylic acid with periodic acid (In the formula, R has the same meaning as above.) A method for producing a 3,3-dimethyl-2-formylcyclopropanecarboxylic acid derivative. 2. The method for producing a 3,3-dimethyl-2-formylcyclopropanecarboxylic acid derivative according to claim 1, wherein the periodic acid is a periodic acid whose aqueous solution exhibits acidity. 3. The method for producing a 3,3-dimethyl-2-formylcyclopropanecarboxylic acid derivative according to claim 1, wherein the reaction is carried out in the presence of a mixed solvent of water and an organic solvent insoluble in water. 4. The ruthenium compound according to claim 1, which is a ruthenium metal, a ruthenium oxide, a ruthenium halide, a ruthenium complex or a perruthenate.
A method for producing a 3-dimethyl-2-formylcyclopropanecarboxylic acid derivative. 5. Iodine acids by-produced by the reaction between 3,3-dimethyl-2- (2-methyl-1-propenyl) cyclopropanecarboxylic acid represented by the general formula (1) and periodate are converted to periodic acid. The 3,3 according to claim 1, wherein the periodate is converted into and recovered as an acid, and the recovered periodic acid is reused in the reaction.
A method for producing a dimethyl-2-formylcyclopropanecarboxylic acid derivative. 6. The amount of periodate used is 2 to 3,3-dimethyl-2- (2-methyl-1-propenyl) cyclopropanecarboxylic acid represented by the general formula (1).
3,3-Dimethyl-2 according to claim 1, which is 3 molar times.
-Method for producing formylcyclopropanecarboxylic acid derivative.