JPH03223273A - Preparation of dehydrorolioride and novel intermediate - Google Patents

Abstract

PURPOSE:To readily prepare dehydrorolioride useful as a perfume for tobaccos, cosmetics, drugs, beverages, foods, etc., in short processes by employing inexpensive and readily available isophorone as a starting raw material. CONSTITUTION:A compound of formula I [R<2>, R<3> are lower alkyl, or R<2> and R<3> together form group of formula II (R is lower alkylene)] is allowed to react with acetic acid in the presence of DMAP and DCC in an organic solvent at 40-100 deg.C to prepare a compound of formula III [R<1> is COCH3, COCH2X (X is halogen)]. The compound of formula III is cyclized in the presence of a base or zink to prepare a lactone of formula IV. The lactone of formula IV is dehydrated with thionyl chloride and the prepared compound of formula V is hydrolyzed in the presence of an acid to prepare the objective compound of formula VI. The compounds of formulas III, IV and V are new compounds and are intermediates for synthesizing the compound of formula VI.

Description

DETAILED DESCRIPTION OF THE INVENTION (Industrial Application Field) The present invention relates to the per se known 2-hydroxy-2°6.6
-) A novel method for producing riftyl-4-oxone chloroquinolitine acetein lactone (hereinafter referred to as dehydroloriolide) and a novel compound useful as a synthetic intermediate for the compound; .

More specifically, the present invention provides a novel method for producing dehydrololiolide represented by the following formula (1), which is useful as a flavor component for tobacco, cosmetics, pharmaceuticals, food and drink products, etc., and a method for synthesizing the compound of formula (1). The following formula (A
) In the formula, R2 and R3 are the same or different and each represents a lower alkyl group, or R2 and R3 represent a lower alkylene group, the broken line represents a double bond, and R3 is absent or the broken line represents a single bond, and R5 represents 10H, and relates to a novel method for producing 2-oxahincro[4,3,OF2/tins represented by the following formula and the compound of formula (A).

Furthermore, the present invention provides the following formula (B), which is useful as a synthetic intermediate for the compounds of formulas (1) and (A):
R' represents COCH3 or 11COCH2X, where X represents a halogen atom, and R2 and R3 have the same meanings as above, 2-alkyloxy or 2-haloalkyloxy-2,6,6- The present invention relates to a novel method for producing dolimethyl-4゜4-(dialkyloxy or alkylenedioquino)cyclohexanones and the compound of formula (B).

Furthermore, the present invention provides the following formula (C), which is useful as a synthetic intermediate for the compounds of formulas (1) and (A-2), in which R1 represents a lower alkyl group, and R2 and R3 have the same meanings as defined above. 2-dialkylphosphonoacetoxy-2,6 represented by
, 6-1limethyl-4,4-(dialkyloxy or alkylene dioxy/)cyclohexanone and the formula (C
) relates to a new method for producing the compound.

(Prior Art) Dehydroloriolide is a known compound discovered as a result of analysis of tobacco aroma components, and several proposals have been made regarding its production method.

For example, it has been proposed to synthesize dehydroloriolide using 3,5.5-trimethylcyclohex-2-en-1-one (hereinafter referred to as isophorone) as a starting material through 6 steps shown in Reaction Formula I below. There is [Brechin on
The Chemical Society on Japan Bu
i1. Chem.

Soc, Japan), 55.1907 (1982)
-Chemistry Letters (Chem, Lett),
63. (1983); Special Publication No. 61-36725,
JP-A-58-167579].

Reaction formula In the above reaction formula, TMS-(11 is trimethylsilyl chloride, hereinafter referred to as HMPA-hexamethylphosphoric acid triamide; M s C12 = methanesulfonyl chloride; Py-pyridine; DBU = 1°8-diazabicyclo[5,4, 0] -7-undeca7, MCPBA-metachloroperbenzoic acid; PDC-pyridinium dichromate, respectively.

In addition to the above, known techniques regarding the synthesis method of dehydrololiolide include, for example, Journal.

On the Chemical Society, Chemical Communications [J, Chem, Soc,.

Chem, Commun, 634 (1966)]:
Chemical Pharmaceutical Bulletin [Ch
em, Pharm, Bull, 16°848 (19
68); Tetrahedron [Tetrahedron, 5
upp1.8. Part l.

1 (1966)); Helvechi Chikara Kimi Chikara
Acta [He lv-Chim, Act a, 5
Yu, 481 (1968); Tetrahedron Letters,
1089 (1971)];
and Biological Chemistry [Agric,
Bio 1. Chem, 1149 (1979) 1 and Japanese Patent Publication No. 55-19218.

(Problems to be Solved by the Invention) However, although the above-mentioned conventional techniques are interesting as chemical reactions, they all involve long and complicated steps, and the yield in each step is not necessarily good. In addition, it required the use of expensive reagents, and as a result, it was not necessarily an industrially satisfactory method for synthesizing dehydrololiolide.

The present inventors conducted extensive research in order to solve the above problems. As a result, cheap isophorone (3,5,
By using the compound of formula (2) as a starting material, which can be easily obtained by reacting (5-trimethylcyclohex-2-en-1-one) with an alcohol and oxidizing the resulting acetal, The present invention was completed by successfully synthesizing the compound of formula (1) with high yield and high purity using only 3 to 5 steps.

It is therefore an object of the present invention to have the above formula (
An object of the present invention is to provide a novel method for producing dehydroloriolide represented by 1).

Another object of the present invention is to provide a novel intermediate useful for the synthesis of the compound of the formula (1), which is a compound of the formula (A) included in the formula (A).
-1) and formula (A-2) and a novel method for producing them.

Still another object of the present invention is to obtain the formula (1) and the formula (A
) is a novel intermediate useful for the synthesis of compounds of formula (B).
) and a method for producing the compounds.

In addition, an object of the present invention is to obtain the formula (1) and the formula (A-
Compounds of formula (C) useful for the synthesis of compounds of formula (2) and of formula (
The present invention provides a method for producing the compound of C).

In this specification, the term "lower" means that the group or compound to which this term is attached has 6 or less carbon atoms.

(Means for Solving the Problems) According to the present invention, the compound of formula (2) is reacted with acetic acid or monohalogenated acetic acid to form a novel formula (B-1) included in formula (B). Alternatively, a new compound of formula (B-2) below is produced, and then, in the case of the compound of formula (B-■), by aldol condensation reaction, or in the case of the compound of formula (B-2), by leformado A cyclization reaction is carried out by a Reformatsky reaction to produce a compound of formula (A-1) included in the above formula (A), and then the compound is subjected to a dehydration reaction to produce a compound of formula (A-1) included in the above formula (A). The target compound of formula (1) described below can be obtained by producing a compound of formula (A2) and then hydrolyzing the compound of formula (A-2).

Alternatively, according to the present invention, a known compound of formula (2) is reacted with dialkylphosphonoacetic acid to form a novel compound of formula (C); is lactonized by Wittig reaction to give a compound of formula (8-2), and then hydrolyzed in the same manner to easily synthesize the target compound dehydroloriolide of formula (1).

The novel synthesis method of the present invention for synthesizing the dehydrololiolide of formula (1) from the compound of formula (2) is shown in a reaction formula:
It can be expressed as below.

Reaction formula (2) () In the formula, R2, R3, R4 and X have the same meanings as described above.

The compound of formula (2), which is the starting material for the method of the present invention, is published, for example, in the Journal of Organic Chemistry.
It can be easily synthesized by reacting inexpensive isophorone with an alcohol in the presence of an acid, according to the method described in J.Stry) 51.253-254 (1986).

The method for producing dehydrololiolide of the present invention will be explained in more detail for each reaction route based on Reaction Formula 2 above.

[r] Method 2 via the compound of formula (B-1) (
The compound of formula (2) is led to the compound of formula (B-1) included in formula (B), and the compound of formula (1) is obtained via an intramolecular aldol reaction.
A method of synthesizing dehydrololiolide.

2-acetoxy-2゜6.6- represented by formula (B-1)
The synthesis of dolimethyl-4.4-(dialkyloxi/or alkylenedioquine)cyclohexanone is performed using the above formula (2).
The compound is easily reacted with acetic acid in an organic solvent in the presence of 4-dimethylaminopyridine (hereinafter referred to as DMAP) and N,N'-dicyclohexylcarbodiimide (hereinafter referred to as DCC). It can be carried out.

The above reaction can be carried out, for example, at a temperature of about 406C to about 100C for about 1 to about 5 hours.

The amount of acetic acid used in this reaction can range, for example, from about 1 to about 2 moles per mole of the compound of formula (2). Further, the amount of DMAP used in the above reaction may be an amount sufficient to act as a catalyst, for example, about 1 g to about 10 g per mole of the compound of formula (2).
For example, DCC is often used in an amount of about 1 to about 2 moles per mole of the compound of formula (2).

Further, as the organic solvent used in the above reaction, for example,
Examples include methylene chloride, chloroform, carbon tetrachloride, and 1,2-dichloroethane. The amount of these organic solvents to be used is not particularly limited, but the range of -conversion can be exemplified in the range of about 10 to about 30 times the weight of the compound of formula (2).

After the reaction is completed, the compound of formula (B-1) can be obtained in high yield and purity by extraction, washing, drying, concentration, and if necessary, using purification means such as column chromatography.

1,2-dihydroxy-2,6,6-drimethyl-4. The synthesis of 4-(dialkyloxy or alkylenedioxy)cyclohexyl acetic acybilactone is carried out using the formula (B-1)
of diisopropylamine and n in an organic solvent.
This can be easily carried out by lactonization by reaction in the presence of lithium diisopropylamide (hereinafter referred to as LDA) prepared from -butyllithium.

The above reaction can be carried out, for example, at a temperature of about -30°C to about -78°C for a reaction time of about 1 to about 5 hours.

In addition, the amount of LDA used in this reaction can be determined, for example, by the formula (
A preferred range of about 1 to about 2 moles per mole of the compound B-1) can be exemplified.

Furthermore, examples of the organic solvent used in the above reaction include tetrahydro7rane, diethyl ether, dimethoxyethane, etc. The amount of such organic solvent used is not particularly limited, but usually in the formula (B=1) For example, the amount may be about 50 to about 200 times the weight of the compound.

After the reaction is completed, the reaction product is extracted, washed, dried, and concentrated according to a conventional method, and if necessary, a purification method such as column chromatography is used to obtain the compound of formula (A-1) in high yield. can be obtained in purity.

The compound of formula (A-2) of the present invention can be synthesized from the metal compound of formula (A-1) obtained by the above reaction.
) can be easily dehydrated using thionyl chloride in an organic solvent.

The above reaction can be carried out, for example, at a temperature of about 0 to about 30°C for a reaction time of about 1 to about 5 hours.

Further, the amount of thionyl chloride used in this reaction is preferably in the range of about 1 to about 5 moles per mole of the compound of formula (A-1).

Further, as the organic solvent used in the above reaction, for example, basic organic solvents such as pyridine, diisopropylethylamine, and triethylamine can be preferably mentioned. The amount of such organic solvent used is not particularly limited, but
Usually, for the compound of formula (A-1), for example, about 20 to
An example is a range of about 50 times the weight.

After the reaction is completed, the reaction product is extracted, washed, dried, and concentrated according to a conventional method, and if necessary, a purification method such as Column Chroma 1 Togelafy is used to obtain the compound of formula (A-2) in high yield. can be obtained in purity.

The dehydrololiolide of formula (1), which is the object compound of the present invention, can be produced from the compound of formula (A-2) obtained by the above reaction by a method known per se, for example, using a water-miscible compound such as acetone, tetrahydrofuran, etc. This can be easily carried out by hydrolysis with an acid such as sulfuric acid, hydrochloric acid, or phosphoric acid in an organic solvent.

After the reaction is completed, the reaction product is extracted and
By washing, drying, concentrating, and using purification means such as column chromatography if necessary, the final target compound of formula (1) can be obtained with high purity and high yield.

[1r] Method via the compound of formula (B-2): from the compound of formula (2) to the compound of formula (B-2), which is a new intermediate included in formula (B), and converting the compound of formula (B- 2) A method for synthesizing the compound of formula (1) via an intramolecular leformadoski reaction of the compound.

A novel compound of formula (B-2) included in formula (B) is prepared by reacting a known compound, a ketoalcohol of formula (2), with a halogenated acetic acid in the presence of DCC and DMAP in an organic solvent. Compounds can be easily synthesized.

The above reaction may be performed, for example, from about 40 to about 1. This can be carried out at a temperature of OO'C for about 1 to about 5 hours.

Examples of the halogenated acetic acid used in this reaction include chloroacetic acid, bromoacetic acid and iodoacetic acid. The amount of the halogenated acetic acid to be used is preferably in the range of about 1 to about 2 moles per mole of the compound of formula (2).

Further, the amount of DCC used in the above reaction may be, for example, about 1 to about 2 mol per 1 mol of the compound of formula (2). Further, the amount of DMAP to be used is, for example, about 10 to about 30 g per 1 mole of the compound of formula (2).

Further, as the organic solvent used in the above reaction, for example,
Examples include 1,2-dibromoethane, methylene chloride, chloroform, and 2-dichloroethane.

The amount of the organic solvent to be used is not particularly limited, but an example of the amount used is usually about 10 to about 30 parts by weight per 1 part by weight of the compound of formula (2).

After completion of the reaction, 2-bromoacetoxy- represented by formula (B-2) is extracted by conventional methods, washed, dried, concentrated, and if necessary, using purification means such as sorbent gel column chromatography. 2゜6.6-drimethyl-4
．． 4-(Dialkyloxy or alkylenedioquine)
Cyclohexanone can be obtained with high purity and high yield.

The thus obtained compound of formula (B-2) can be converted into a hydroquinolactone represented by formula (A-1) using the intramolecular leformadoski reaction known per se.

In this reaction, for example, zinc particles are packed into a dropping funnel, washed with dilute hydrochloric acid, and then filled with tetrahydrofuran (hereinafter referred to as THF).
This can be carried out by washing with a solvent such as (referred to as )), then, for example, dropping a σ-halogen ester such as ethyl bromoacetate to activate the zinc particles in advance, and further washing with a solvent such as THF.

By bringing the bromoacetate of formula (B-2) into contact with the zinc particles activated as described above, an intramolecular leformadoski reaction occurs, producing a hydroxylactone represented by formula (AI).

This reaction is usually carried out at about 50 to about 80°C.

The reaction time can generally be about 1 to about 5 hours.

At this time, the compound of formula (B-2) can be diluted with an organic solvent in advance. Examples of such organic solvents include tetrahydrofuran, benzene, toluene, and the like. The amount of organic solvent used is often from about 5 to about 10 parts by weight per 1 part by weight of the halogen ester. After completion of the reaction, the product is washed, dried and concentrated, and if necessary, purified by column chromatography etc. to obtain 1,2-dihydroxy-2,6,6-drimethyl-4 represented by formula (A-1). .4-(Dialkyloxy or alkylenedioquine)cyclohequinyl acetic acid lactone can be obtained with high purity and high yield.

The compound of formula (A-1) is subjected to a dehydration reaction to form a compound of formula (A-2) in the same manner as described above, and then hydrolyzed to form the final target dehydrololiolide of formula (1). I can do something.

[11] Method via Witschig reaction: Formula (2)
A compound of formula (C), which is a new intermediate, is obtained from the compound of
Intramolecular Wittig of the compound of formula (C)
A method of synthesizing the compound of formula (1) via reaction.

By reacting a known compound, a ketoalcohol of formula (2), with a C-C2 dialkylphosphonoacetic acid in an organic solvent in the presence of DCC and DMAP, a novel formula (
Compound C) can be easily synthesized.

The above reaction can be carried out, for example, at a temperature of about 40 to about 100° C. for about 1 to about 5 hours. The amount of dialkylphosphoacetic acid used in this reaction is preferably in the range of about 1 to about 2 moles per mole of the compound of formula (2).

The amount of DCC used in the above reaction may be, for example, about 1 to about 2 moles per mole of the compound of formula (2).

The amount of DMAP to be used is, for example, about 19 to about 10 g per 1 mole of the compound of formula (2).

Further, as the organic solvent used in the above reaction, for example,
Examples include dichloromethane, chloroform, 2-dichloroethane, and carbon tetrachloride.

The amount of the organic solvent to be used is not particularly limited, but - for yield, approximately 1 part by weight of the compound of formula (2) is used.
An example of the amount is about 0 to about 30 parts by weight.

After the reaction is completed, 2-dialkylphosphonoacetoxy-2゜6.6 represented by formula (C) is extracted by conventional methods, washed, dried, concentrated, and if necessary, using purification means such as column chromatography. -Dorimethyl-4.
4- (Dialkyloxy or alkylenedioxy)
Cyclohexanone can be obtained with high purity and high yield.

By subjecting the resulting compound of formula (C) to an intramolecular Witsch reaction in an organic solvent in the presence of a base, it can be easily converted to formula (
1,2-dihydroxy-2,6,6 represented by A-2)
-1-Remethyl-4,4-(dialkyloxy or alkylenedioxy)cyclohexyl acetic acid lactone can be obtained.

Examples of the organic solvent used in this reaction include tetrahydroctane, toluene, dimethoxyethane, diethyl ether, and the like.

The amount of the solvent to be used can be selected as appropriate, but for example, about 50 to about 100 parts by weight per 1 part by weight of the compound of formula (C).
Examples include amounts such as parts by weight.

Examples of the base catalyst used in this reaction include sodium hydride, potassium hydride, lithium hydride, sodium methoxide, and sodium ethoxide. The amount of the base catalyst to be used is not strictly limited, and for example, it can be used in an amount of about 1 to about 2 mol per 1 mol of the compound of formula (C).

This intramolecular Wittig reaction can be carried out using the formula (
This can be carried out by adding the compound C) and reacting for about 1 to about 5 hours. After completion of the reaction, the lactone of formula (A-2) can be obtained with high purity and high yield by using purification means such as extraction, washing, drying, concentration and, if necessary, column chromatography.

The compound of formula (A-2) can be easily converted to the final target compound of formula (1) by hydrolysis treatment in the same manner as described above.
) can lead to dehydrololiolide.

(Example) Hereinafter, the method of the present invention will be explained in more detail with reference to Examples.

Example 1 2-hydroxy-2,6,6-1-limethyl-4,4-(ethylenedioxy)cyclohexanone [compound of formula (2)] 1-Og (4,7mm01),
Acetic acid 395mg (6.6mmol), DMAP
Prepare 50 mg and 20 mQ of dry dichloromethane,
Cool the mixture to OoC and add DCCI with stirring.

Add 2g (5.6 mmol) little by little. After reacting at room temperature for 3 hours, the mixture is heated and further reacted under reflux conditions for 20 hours. After cooling, it is filtered using Celite to remove insoluble matter. The filtrate was washed with ice-cooled 0.5N hydrochloric acid, neutralized with an aqueous sodium bicarbonate solution, and dried to obtain 2.7 g of a crude product. This crude product was purified by column chromatography using silica gel 509 (hexane:ethyl acetate=1O:1 to 5:1), and a new compound of formula (B-1), 2-acetoxy-2,6
800 mg (yield = 67%) of ゜6-drimethyl-4.4-(ethylenedioxy)cyclohexanone was obtained.

In addition, the structure of this new compound was determined by 'H-NMR and 'C
- Confirmed by NMR.

'H-NMR (CDC4,) δppm 1.24 (6) 1. s) 1.53 (3H
,s) 2.03(3H,s)1.73-2.77(
4H, m) 3.92-4.04 (4H, m)3C-
NMR (CDCQ,) δppm 20.98 26.12 28.24 43
．． 68 44.0044.92 63.50 64.5
9 80.19 +06.68169.85 211
．． 67 Example 2 The title compound was synthesized in the same manner as in Example 1.

Its physical property values are shown in Table-1.

Table = 1 Example 3 100 mC of dry tetrahydrofuran (THF) and 1.1 mQ (7°83 mmol) of diisopropylamine were charged into a flask, and n-butyllithium (
1,6N) 3.9mQ (6,26mmol) was added to prepare lithium diisopropylamide (LDA). In this LDA solution, 2-acetoxy-2,6,6-drimethyl-4.4 diluted in advance with 10 g of dry THF was added.
-(ethylenedioxy)cyclohexanone [formula (B-1
) compound 1800mg (3.13mmol) -78
The mixture was added dropwise at a temperature of °C, and the mixture was further reacted at the same temperature for 3 hours. After the reaction is complete, add 20 mQ of ammonium chloride aqueous solution, return to room temperature, extract, wash, and dry to obtain crude product 8.
5 (h++9 was obtained.

This crude product was purified by silica gel column chromatography (
Purified with hexane:ethyl acetate-2:l), formula (A-1
) new compound 1,2-dihydroxy 2.6.61-limethyl-4,4-(ethylenedioquine)chlorhexyl acetic acid lactone 640 mg (yield -80%
) was obtained. The structure of this new compound was confirmed by 'H-NMR and I3C-NMR.

'H-NMR (CDC (2s) δppm 1.00 (3H, s) 1.17 (3H,
s) 1.59 (3H, s) 1.73 (2H, s)
1.90 (IH, br, s) 2.16-2.18 (
IH, m) 2.41 (IH, d, J = 17.4Hz
) 2.95 (IH, d, J47.4Hz) 2.89
(IH, br, s) 3.80-4.06 (4H, m) NMR (CDC12,) δppm 20.65 23.20 27.48 36
．． 80 41.2445.03 45.57 63.2
3 64.75 81.2289.40 106.68
174.833C Example 4 The title compound included in formula (A-1) was synthesized in the same manner as in Example 3. Its physical property values are shown in Table-2.

(Left blank below) Example 5 1,2-dihydroxy-obtained in Example 3 was placed in a production flask of Table 2.
2,6,6-drimethyl-4,4-(ethylenedioxy)cyclohexylacetic and lactone [formula (A
-1) Compound] 800+n9 (3.1 mmol) and 40 ml of dry pyridine were charged and cooled to 0°C, thionyl chloride l, l mQ (15 mmol) was added thereto, and the mixture was reacted at the same temperature for 3 hours. After the reaction was completed, 10 mQ of water was added, stirred for 30 minutes, extracted with ether, washed with 6N hydrochloric acid to remove pyridine, washed with an aqueous sodium bicarbonate solution and saturated brine, dried over magnesium sulfate, and distilled off the ether to obtain a crude product. 620 mg of the product was obtained. This crude product was purified by silica gel column chromatography (hexane:ethyl acetate-5:l
~2:l) to produce a novel compound of formula (A-2), 2-hydroxy-2,6,6-drimethyl-4. ! (Ethylenedioquine) chlorhequinidene acetysoquacidolactone 620+++9 (yield -93%) was obtained.

In addition, the structure of this new compound was determined by 'H-NMR and 'C
- Confirmed by NMR.

H-NMR (CDC(23) δppm 1.29 (3H, s) 1.37 (3H,
s) 1.70 (3H, s) 1.67'2.44 (4H
, m) 3.80-4.15 (4H, m) 5.72 (
IH,s) ”CNMR (CDCQ3) δppm 25.04 25.42 30.46 35
．． 04 46.7648.23 63.56 65.0
7 86.96 107.871+3.29 171.
53 181.12 Example 6 The title compound included in formula (A-2) was synthesized in the same manner as in Example 5.

Its physical property values are shown in Table 3. show.

(Margin below) Table Example 7 Compound 57 of formula (A-2) obtained in Example 5 in a flask
0 m9 of acetone, IOmQ of acetone, and 3 mQ of 5% sulfuric acid were charged, and the mixture was heated under reflux for 5 hours. After cooling, the reaction solution was poured into an aqueous sodium bicarbonate solution to neutralize it, extracted with ether, washed, dried over magnesium sulfate, and recovered the ether.
The residue was purified by silica gel column chromatography (hexane:acetic acid f-4=2:l) to obtain 380 mg of the target compound of formula (1) (yield -81.8%). The structure of this compound is 'H-N MR and 13C-NMR
It was confirmed that it was dehydroloriolide.

H-N MR (CD CQ 3 ) δppm 1.31 (3H, s) 1. ．． 43 (3H
, s) 1.60 (3H, s) 2.46 (2H1s)
2.82 (II-1, d,, l13.6Hz) 2.9
7 (IH, d, Jl, 3.6Hz) 5.93 (IH
, s) Summer 3CN M R (CD CQ 3) δpp
m 26.01 26.77 29.7553.98
86.09 114.48178.35 204.36 35.77 53.59 170.28 Example 8 10g of ketoalcohol of formula (2) in a flask (46,
7 mmol), dry 1,2-dibromoethane 200 m
Q, bromoacetic acid 13,h (94 mmol) and 500 mg of DMAP were charged, cooled to 5°C, and DCC19,h (94 mmol) was added little by little.

The internal temperature rose from 5°C to 43°C due to fever. Thereafter, the mixture was allowed to react at room temperature for about 20 hours. After the reaction was completed, it was filtered through Celite, the filtrate was washed, dried, and concentrated, and the residue was purified by phosphoric gel column chromatography (hexane-ethyl acetate-
20.1 to 5:l) to obtain 12.5 g (yield -79.6%) of a new compound of formula (B2). The structure of this new compound was confirmed by 'H-NMR and C H δ C δ N MR.

NMR (CDCQ3) ppm 1.24 (3H, s) 1.26 (3H, s
) 1.57 (3H, s) 1.75-2.77 (4H,
m) 3.83 (2H, s) 3.88-4.15 (4
H, m) NMR (CDCQ3) ppm 25.85 28.07 43.35 43.
57 44.8763.50 64.53 81.98
106.30165.84210.69 Example 9 The title compound included in formula (B-2) was synthesized in the same manner as in Example 8.

Its physical property values are shown in Table 4. show.

(The following is a blank space) Table 4 Example 1 (Ethylenedioquine) chlorhexyl acetate lactone [compound of formula (A-1)].

Fill a dropping funnel without a side tube with Zn grains, wash thoroughly with 2N hydrochloric acid and then with tetrahydrofuran, and dropwise add ethyl bromoacetate to cause the Leformadski reaction to activate the Zn grains. These Zn grains are treated with tetrahydro7
After washing with 2-bromoacetoquine-2,6,6-
Trimethyl 4.4-(ethylenedioxy)cyclohexanone [compound of formula (B-2)] 1.19 (3,
A solution prepared by preliminarily diluting 3 to 1) to 5 ml of tetrahydro-7 is added dropwise to the Zn grains to cause a reaction. The effluent was extracted with ether, and the ether layer was washed with dilute hydrochloric acid and water, neutralized, and dehydrated to remove the ether. The obtained crude product was purified by silica gel column chromatography (hexane:ethyl acetate = 2:l) to obtain 440m of the compound of formula (A-1).
g (yield=82.2%) was obtained. 'H-N of this compound
MR and "C-NMR are based on the formula (A-
It was the same as 1).

Example 11 2-diethylphosphonoacetoxy-2,6,6-trimethyl-4,4-(ethylenedioxy) Schiff flask with the formula (
2) Keto alfur 5. Og (23.4 mmol),
9.29 mg of diethylphosphonoacetic acid, 250 mg of DMAP, and dry dichloromethane roomQ were charged, and 8.29 DCC (39°8 mmol) was added little by little while stirring. This mixture was reacted at room temperature for 3 hours, then further heated and reacted under reflux conditions for 4 hours. After the reaction was completed, the mixture was cooled, filtered through Celite to remove insoluble matter, washed with ice-cooled 0.5N hydrochloric acid, neutralized, and dried over magnesium sulfate. After concentration, the obtained crude product was subjected to silica gel column chromatography (hexane:ethyl acetate=
2-diethylphosphonoacetoxy-2,6,6-, a novel compound encompassed by formula (C)
Dolimethyl-4.4-(ethylenedioxy)cyclohexanone f3. oy C yield = 66%).

In addition, the structure of this new compound was determined by 'H-NMR and 'C
- Confirmed by NMR.

'H-NMR (CDC123) δppm l-24 (68, m) 1.34 (6B
, s) 1.42 (2H, s) 1.55 (3H, s)
1.8-2.1 (4H, m) 3.92-4.26 (
8H, m) 13CN M R (CD CQ 3) δppm 16.04 16.32 26.09 2
8.18 31.2137.12 43.62 44.
81 52.19 62.4262.69 63.45
64.53 81.38106.57164.43
164.75 211.02 Example 12 Compound].

In the same manner as in Example 11, the title compound included in formula (C) was synthesized from the dialkyloxyketol included in formula (2). The analytical values are shown in Table 5.
(Margin below) Table 5 Example 1 3 Sodium hydride (62.6%) in flask 21]
My (5.5 mmol) and 50 m (i) of dry tetrahydrofuran were charged and stirred and cooled to 5-10°C. Into this suspension was added 1.969 (5,0 mmol) of the compound of formula (C).
A solution prepared by dissolving 5mQ of dry tetrahydro-7rane was added thereto, and the mixture was reacted at room temperature for 1 hour.

After the reaction was completed, 10 ml of ammonium chloride aqueous solution was added, extracted with ether, washed and dried, and then subjected to silica gel column chromatography (hexane:ethyl acetate-5=1-2:1).
) to give 730 mg of the compound of formula (A-2) (yield=
61%). 'H-NMR and 'C-
The NMR was consistent with that of the compound of formula (A-2) obtained in Example 5.

(Effects of the Invention) According to the present invention, using isophorone, which is inexpensive and easily available on the market, as a starting material, the compound expressed by formula (1), which is useful as a flavoring agent for tobacco, cosmetics, pharmaceuticals, food and drink products, etc. Provided is a method for producing dehydrololiolide in a short process and by easy synthetic means, which is extremely advantageous industrially.

Furthermore, according to the present invention, 2-acetoxy or 2-haloacetoxy-2,6,6-drimethyl-4,4-(alkylene dimethyl oxy or dialkyloxy) cyclohexanones: 1, 2 represented by formula (A)
-dihydroxy or 2-hydroquine-2,6,6-
Dolimethyl-4.1-(alkylenedioxy or dialkyloxy)-cyclohexyl acetic acid lactones and 2-dialkylphosphonoacetoquine-2,
Novel compounds are provided, such as 6,6-1-limethyl 4,4-(alkylenedioxy or dialkyloxy)cyclohexanones.

Claims (5)

[Claims] (1), the following formula (2) ▲There are mathematical formulas, chemical formulas, tables, etc.▼ (2) In the formula, R^2 and R^3 are the same or different, and each represents a lower alkyl group, or R^2 and R^3 together represent a group of the formula ▲There are mathematical formulas, chemical formulas, tables, etc.▼, where R represents a lower alkylene group, 2-hydroxy-2,6,6-trimethyl represented by −
4,4-(dialkyloxy or alkylenedioxy)cyclohexanone is reacted with acetic acid or monohalogenated acetic acid in the presence of N,N'-dicyclohexylcarbodiimide and 4-dimethylaminopyridine to obtain the following formula (B) ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (B) In the formula, R^2 and R^3 have the same meanings as above, and R^1 represents COCH_3 or COCH_2X, where X
represents a halogen atom, 2-acetoxy or 2-halo-acetoxy-2,6,6-trimethyl-4,4-(alkylenedioxy or dialkyloxy)cyclohexanone represented by is produced, and then the formula (B) The compound is cyclized in the presence of a base or zinc, and the following formula (A-1) ▲There are mathematical formulas, chemical formulas, tables, etc.▼ (A-1) In the formula, R^2 and R^3 are as described above. 1,2-dihydroxy-2,6,6-trimethyl-4,4-(alkylenedioxy or dialkyloxy)cyclohexylacetic acid lactone, which has the same meaning, is produced and then dehydrated to produce the following formula ( A-2) ▲There are mathematical formulas, chemical formulas, tables, etc.▼ (A-2) In the formula, R^2 and R^3 have the same meanings as above, and 2-hydroxy-2,6,6 is represented by -trimethyl-4,
The following formula (1) is characterized by producing 4-(dialkyloxy or alkylene dioxy) cyclohexylidene acetic acid lactone and hydrolyzing the compound of formula (A-2) in the presence of an acid. There are mathematical formulas, chemical formulas, tables, etc. ▼ (1) 2-Hydroxy-2,6,6-trimethyl-
A method for producing 4-oxo-cyclohexylidene acetic acid lactone (dehydrololiolide). (2), the following formula (2) ▲There are mathematical formulas, chemical formulas, tables, etc.▼ (2) In the formula, R^2 and R^3 have the same meaning as stated in claim 1, 2- expressed as Hydroxy-2,6,6-trimethyl-
The following formula (C) obtained by reacting 4,4-(dialkyloxy or alkylenedioxy)cyclohexanone with dialkylphosphonoacetic acid in the presence of N,N-dicyclohexylcarbodiimide and 4-dimethylaminopyridine ▲Math. There are chemical formulas, tables, etc.▼(C) In the formula, R^2 and R^3 have the same meanings as above, and R^
4 represents a lower alkyl group, 2-dialkylphosphonoacetoxy-2,6 represented by
, 6-trimethyl-4,4-(alkylenedioxy or dialkyloxy)cyclohexanone was obtained, then the formula (
The compound of C) is lactonized in the presence of a base to form the following formula (
A-2) ▲There are mathematical formulas, chemical formulas, tables, etc.▼ (A-2) In the formula, R^2 and R^3 have the same meanings as above, and 2-hydroxy-2,6,6 is represented by -trimethyl-4,
The following formula (1) is characterized in that 4-(alkylenedioxy or dialkyloxy)cyclohexylidene acetic acid lactone is produced and the compound of formula (A-2) is hydrolyzed in the presence of an acid. , chemical formulas, tables, etc. ▼(1) 2-Hydroxy-2,6,6-trimethyl-
A method for producing 4-oxo-cyclohexylidene acetic acid lactone (dehydrololiolide). (3) The following formula (B) ▲There are mathematical formulas, chemical formulas, tables, etc.▼ (B) In the formula, R^1, R^2, and R^3 have the same meaning as stated in claim 1, and are represented by 2-acetoxy or 2-halo-acetoxy-2,6,6-trimethyl-4,4-(dialkyloxy or alkylenedioxy)cyclohexanones. (4) The following formula (A) ▲There are mathematical formulas, chemical formulas, tables, etc.▼ (A) In the formula, R^2 and R^3 have the same meaning as stated in claim 1, and the broken line indicates a double bond. 2-oxabicyclo[4,3,0]nonanes represented by: and R^5 does not exist, or the broken line indicates a single bond, and R^5 indicates -OH. (5) The following formula (C) ▲There are mathematical formulas, chemical formulas, tables, etc.▼ (C) In the formula, R^2, R^3, and R^4 have the same meaning as stated in claim 2, and are represented by 2-dialkylphosphonoacetoxy-2,6
, 6-trimethyl-4,4-(dialkyloxy or alkylenedioxy)cyclohexanone.