JPS6117531A - 6-substituted tetrahydroindanone and its preparation - Google Patents

Abstract

NEW MATERIAL:A 6-substituted tetrahydroindanone shown by the formula I [R is lower alkyl, or -SIR3'(R' is lower alkyl)]. EXAMPLE:6-Ethoxy-4,5,8,9-tetrahydroindanone. USE:An intermediate for preparing perfume of drugs, and a raw material for preparing a cis-2,3-di-substituted cyclopentanone such as novel compound shown by the formula III [R''' is >=2C lower alkyl, preferably 2-4C alkyl, or -SIR3'(R' is preferably CH3)] which is an intermediate for preparing methyl jasmonate shown by the formula II especially useful in the field of perfume. PREPARATION:2-Cyclopentenone shown by the formula V and a 2-bustituted butadiene shown by the formula VI are subject to Diels-Alder reaction in the presence of absence of a solvent at 180-400 deg.C, preferably at 200-300 deg.C at atmospheric pressure or under pressure, and distilled under reduced pressure, to give a high-purity compound shown by the formula I.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to 6-substituted tetrahydroindanones, which are attracting attention as intermediates for producing perfumes and pharmaceuticals, particularly methyl jasmonate useful in the field of perfumes, and methods for producing them.

More specifically, the present invention is directed to the following formula (6), where R is a lower alkyl group, preferably a 01-C4 alkyl group, or -StR; (here, R' is a lower alkyl group, preferably a C1-C2 alkyl group). The present invention relates to a 6-substituted tetrahydroindanone, which has not been described in any literature, and is represented by

The present invention also provides 2-cyclobentenone represented by the following formula (7) and the following formula (8), where R is a lower alkyl group or -5tR,' (where R' is a lower alkyl group) It also relates to a method for producing the compound of formula (6), which is characterized by reacting a 2-substituted butadiene represented by the formula (6).

The compound of formula (6) of the present invention is of the following formula (4)', which is attracting attention as an intermediate for the production of methyl jasmonate, where R' is a lower alkyl group of 02 or more, preferably C2
-C4 alkyl group or -SiR: (Here, R' represents a lower alkyl group, preferably a methyl group)
Including cis-2,5-disubstituted cyclopentanone not described in the literature, represented by the following formula (4), where R has the same meaning as described for formula (6). cis-2,
It is useful as an intermediate in the production of 3-disubstituted cyclopentanone.

Hitherto, compounds in which R is a methyl group among the compounds of the above formula (4) and methods for producing the same have been known (/.

Org, Chem, Vol. 40, Floor 4. 1975). According to this known method, the compound is produced by a complicated and multi-step reaction represented by the following process formula, H H .

The present inventors conducted research to avoid such a complicated and industrially disadvantageous multi-step method and to produce the above compound. As a result, by using the easily available 2-cyclobentenone of the formula (7) and the 2-substituted butadiene of the formula (8) as starting materials, the 6-substituted nato 2 of the formula (6) of the present invention
Hydroindanone is easily obtained with good yield and good selectivity, and by treating the compound of formula (8) with a mild oxidizing agent such as Then, cis-2,3 represented by the above formula (4)
- Disubstituted cis-methyl jasmonate can be produced industrially and advantageously, and methyl jasmonate can be easily obtained even when a compound in which R is a group other than a methyl group is used as the compound of formula (4). discovered.

Accordingly, an object of the present invention is to provide 6-substituted tetrahydroindanones useful in the perfume and pharmaceutical manufacturing fields and methods for their production.

The above objects and many other objects and advantages of the present invention will become more apparent from the following description.

Using the compound of formula (6) of the present invention, cis-2,3-disubstituted cyclopentanone represented by the formula (4) including the compound of formula (4)' can be easily formed.

This reaction can be easily carried out, for example, by treating the monosubstituted tetrahydroindanone represented by formula (6) with an oxidizing agent having a mild oxidizing action.

The formula (jl) 6-substituted tetrahydroindanone of the present invention is represented by the following formula (7), 2-cyclobentenone represented by the following formula (8), where R is defined in the above formula (6). It can be obtained by reacting 2-substituted butadiene represented by the same meaning as the formula (6) of the present invention obtained.
The compound can be easily converted into the cis-2,5-disubstituted cyclopentanone of the formula (4), for example, by treatment with an oxidizing agent, and the compound of the formula (4) can be converted, for example, to the cis-2,5-disubstituted cyclopentanone of the formula (5).
); By reacting with a reagent, the following formula (2), H.

However, in the formula, R represents a lower alkyl group or -5iR7 (here, R' represents a lower alkyl group), and it can be easily converted into a 2-epi-jasmonic acid ester represented by the following formula. Furthermore, the 2-bijasmonic acid ester of formula (2) is converted into the following formula (31, MOR (3
1 In the formula, Jf is an alkali metal atom such as Lt, N
a, etc., and R represents a lower alkyl group, preferably a methyl group, by reacting with methyl alcohol in the presence of a metal alcoholade represented by the following: methyl jasmonate represented by the following formula (1) can be converted into.

In addition to the usage example of forming methyl jasmonate of formula (1) from the compound of formula (4), the present compound 6-
A method for producing a compound of formula (4) including a compound of formula (4)' from a substituted tetrahydroindanone and an example of producing the compound of the present invention of formula (6) can be shown as shown in the process diagram below.

Formula (4) Formula (2) Formula (1) 6-alkoxy- or 6-drialkylsilyloxy 4.5,8.9-tetrahydroindanone is the 2-cyclobentenone of the above formula (7) and the formula It can be easily produced by subjecting the 2-substituted butadiene (8), ie, 2-alkoxy- or 2-trialkylsilyloxy-butadiene, to a Diels-Alder reaction in the presence or absence of a solvent. The reaction is preferably carried out under heating conditions of, for example, about 80°C or higher, and about 1
It is more preferable to employ an altitude of 800 or more, for example, about 1
Altitudes of the order of 80 DEG to about 400 DEG -1 m, preferably about 200 DEG to about 800 DEG C., are sometimes employed. The reaction can be carried out under atmospheric or pressurized conditions 1, for example in a pressure vessel under naturally occurring pressure conditions.

Specific examples of 2-alkoxy-butadiene of the above formula (8) include 2-methoxy-butadiene, 2-ethoxy-butadiene, 2-n-propoxy-butadiene, 2-n-propoxy-butadiene,
Examples include -iso-propoxy-butadiene, 2-n-butoxy-butadiene, 2-'1so-butothene-butadiene, 2-tart-butoxy-butadiene, and specific examples of 2-trialkylsilyloxybutadiene. Examples include trimethylsilyloxybutadiene.

In addition, the above solvent may be an inert organic solvent, such as benzene, toluene, xylene, n-hexane,
Mention may be made of hydrocarbon solvents such as n-pebutane. These solvents may be used alone or in a mixture of two or more.

-Substituted tetrahydroindanone, i.e. 6-alkoxy, also L (' is 6-drialkylsilyloxy4.5
, 8.9-tetrahydroindanone can be obtained with high purity. If desired, further purification by silica gel column is possible.

For example, specific examples of the starting material formula (8) compound described above and [
7. 2-alkoxy-1 mentioned above (7 or 6-alkoxy body which is an adduct of 2-trialkylsilyloxy-butadiene and 2-cyclobentenone of formula (7) [, < is 6-trialkyl Examples include silyloxy derivatives.

In the present invention, in order to produce the cis-2,8-disubstituted cyclopentanone of formula (4) from ↑ff1e)6-**tetrahydroindanone, ozone depletion is preferably used. For example, use ozone gas as an inert organic solvent at low rm? 6) The desired compound of formula (4) can be obtained with high purity and a high yield by converting the compound into on-nide and then adding a reducing agent without isolation. In the case of using another oxidizing agent, the first ``reducing agent'' can be omitted.

The reaction is preferably carried out at as low a temperature as possible;
For example, when ozone is used, the temperature is from room temperature to about -100'O, preferably from about 10' to about -100'O, particularly from about -20°C to about - 80'O
Ozonation is adopted under image width conditions of approximately When reducing with a reducing agent, a warmer temperature can be used, approximately -10°C.
~ Room temperature is good! l:t, <, more preferably about -10°
C to about 20°C.

In addition, the solvent used (2) is an inert organic solvent that is liquid at the reaction temperature, for example, alcohols such as methanol, methanol, ethyl acetate, methylene chloride, esters,
...Rogenated hydrocarbons can be used alone or in combination. As the reducing agent, for example, zinc dust-acetic acid or zinc oxide, trivalent phosphorus compounds such as triphenylphosphine, or dimethyl sulfide can be used. Alternatively, Pd-C
Catalytic hydrogen reduction can also be carried out using 1pt and other various reduction catalysts. After the completion of the reaction, if the insoluble reducing agent remains in the reaction solution, the compound of formula (4) can be obtained by washing with water (1, washing with water, collecting the oil phase, and obtaining the compound of formula (4), if desired. The compound of formula (4) can be obtained by removing the solvent using conventional methylene chloride. By deducting the formula (4)′ obtained in this way, the above formula (
4) Specific examples of Yoko-Shiichiike → Tanhi Gomono are 2 and 3
-cis-8-carbomethoxymethyl-2-formylmethyl-l-cyclopentanone, 2.8-cis-8-carboethoxymethyl-2-formylmethyl-1-cyclopentanone, 2.3-cis-3 −
Carbo-1so-propoxymethyl-2-for ξ-methyl-1-cyclopentanone, 2.8-cis-8-carbo-n-butoxymethyl-2-for-methyl-1-cyclopentanone, 2.8-cis-
8-carbo180-butoxymethyl-2-formylmethyl-1-cyclopentano/,2,8-cis-3-carbotert-butoxymethyl-2-formylmethyl-1-
Cyflopentanone, 2,8-cis-3-carbotrimethyl 2τxymethyl-
Examples include 2-formylmethyl-1-cyclopentanone.

Hereinafter, an example of the use of cis-2,8-disubstituted cyclopentanone of the formula (4) obtained as described above and E7 will be used to produce methyl jasmonate of the formula (1) from the compound. This will be explained using an example.

The production of the 2-epi-jasmonic acid ester of the formula (2) is carried out by converting the compound of formula (4) to the following formula (5), R': P=Ch
CIt2CM, (s) where R“
can be easily obtained with good yield and selectivity by reacting with the Uinotenohi reagent represented by the above formula (also synonymous with). , the following formula (5)′,
R';I"CHCH,CH2X" (5) '
However, in formula 7, R" has the same meaning as above, X is preferably halogen, and < represents C1, Br or I. It can be prepared by reacting with a base. Examples of the bases used are For example, butyl lithium, phenyl lithium, lithium diethylamide, sodium ethoxide, sodium hydride, sodium amide, potassium hydride, potassium chloride, etc. can be dissolved. Although there are no restrictions, it is preferable to use approximately equivalent amounts or slightly less amounts relative to the compound of formula (5)' above.The reaction is preferably carried out in a solvent under an inert gas atmosphere, such as nitrogen gas. Examples include small active gases such as , helium, and argon.The reaction is preferably carried out at a temperature of about 0°C or higher, and for example, a temperature of about 0'0-f150°C can be used. Anhydrous solvents are preferred (2) Specific examples of solvents include n-hexane, cyclohexane, pentane, benzene, toluene, diethyl ether, dioxane, tetrahydrofuran, dimethyl sulfoxide, #
, 7V-dimethylformamide, dimethoxyethane, and diglyme. These can be used alone or in combination.

Thus, [2] can be formed by combining the Wittstig reagent of formula (5) with the cis-2,8-disubstituted cyclopentanone of formula (4), i.e., cis-2,8-2-formylmethyl-8
-carbalkoxymethyl- or cis-2,8-2
-Forvalmethyl-8-carbosilyloxymethyl-1-
The reaction with cyclopentanone is preferably carried out by contacting the compound of formula (4) and the compound of formula (5) in an organic solvent under an inert gas atmosphere as described above. Examples of the solvent include the same organic solvents as in Example [7] for forming the compound of formula (5) above.

Regarding the selection of the solvent, the same solvent as used for forming the compound of formula (5) may be selected, or a different solvent may be selected.

Therefore, it is preferable to use an anhydrous solvent. Since the reaction proceeds photometrically even at room temperature, heating or cooling is not necessarily required, but such means can be employed if desired. For example, the temperature can be about 0° 0 to about the reflux temperature of the solvent used. The reaction operation is performed using the formula (
4) It is preferable to carry out E7 while dropping either the compound or the compound of formula (5) onto the other. The amount of the Kuinotetsubi reagent of formula (5) to be used relative to the compound of formula (4) can be selected as appropriate, for example, about 1 to about 2 times the molar amount, more preferably about 1-fJl, about 5 times the molar amount. Most often used.

After the reaction is completed, the reaction solution is directly extracted with an organic solvent such as hexane, chloroform, methylene chloride, etc., or diluted hydrochloric acid is added to deactivate excess phosphorane, and the above-mentioned After extraction with a solvent, the solvent can be recovered and purified by distillation or column chromatography.

As mentioned above, a typical example of Nisder 2-evi-jasmonate of formula (2) obtained by (7) is, for example, 2-
Methyl shrimp jasmonate, 2-ethyl shrimp jasmonate, n-propyl 2-equicious jasmonate, inglovil 2-shrimp jasmonate, n-butyl shrimp jasmonate, 2-isobutyl shrimp jasmonate, 2-
Examples include shrimp jasmonic acid tert-butylene ester and 2-shrimp 7-yasmonic acid trimethylsilyl ester.

The 2-shrimp jasmonic acid ester of the formula (2) obtained as described above is converted to the 2-shrimp jasmonic acid ester of the formula (8) MOR (in the formula, M
represents an alkali metal atom such as Li, Nα, K (2, R
represents a lower alkyl group, preferably a methyl group) with methanol in the presence of a metal alcoholade. Methanol can also be utilized in the form of methanol-containing organic solvents. Examples of organic solvents (2 include benzene, toluene,
Mention may be made of hydrocarbon solvents such as xylene, n-hexane, n-heptane and the like.

The reaction can be easily carried out by bringing the compound of formula (2) into contact with methanol in the presence of the compound of formula (8). Since the reaction proceeds at room temperature, there is no need for cooling or heating, although such conditions can be employed if desired. For example, about 0'O-Leopard 7
A temperature of about 0'O can be exemplified. This reaction causes side chain ebimerization, converting the side chain of the five-membered ring ketone in formula (2) from cis to trans, and at the same time, a transesterification reaction occurs, and in formula (2), R Even in a compound of formula (2) in which R is other than methyl, R is converted to a methyl group2, and methyl jasmonate is obtained as an example shown in the following formula.

Methyl Jasmonate In the above reaction, the amount of the metal alcoholade of formula (8) to be used can be selected as appropriate, and a catalytic amount is sufficient.

For example, the amount used may be about 5 to about 20 weight percent based on the 2-shrimp jasmonic acid ester of formula (2). More preferably, it is about 5 to about 15% by weight. The amount of methanol to be used can be selected as appropriate, but it is usually about 50
It is preferable to use about 20 times (weight) or more, and about 20 times fJ100 to about 200 times.

After the reaction, the duck alcoholade is neutralized, for example, with dilute hydrochloric acid, and then extracted with an organic solvent such as methylene chloride, hexane, ether, etc.2, and the solvent is distilled off under reduced pressure (2.
The desired methyl jasmonate formula (1) can be obtained with high purity and high yield.

Moreover, if desired, it can be easily slid by column chromatography or other loading means.

Example 1 Preparation of 6-nitoxy 4.5,8.9-tetrahydroindanone [formula (6)] In a 100 d autoclave, 2-cyclobentenone 1
6. Of and 2-ethoxybutadiene57. Includes Of(
2, 240-2so°CcEeFa-react. After cooling the reaction mixture, the target product, 6-nitoxytetrahydroindanone, was obtained by rectification under reduced pressure at a yield of 2452%.
Obtained.

B, p, :100~]05'O/1.5 cylinder B' gIR
j liquid film): ] 788.1655 閤-1HM'E (
C, C14): δ4.88 (I If, m),
3.60 (21-J, q), 1.22 (8H.

t) Example 2 Preparation of 6-trimethylsilyloxy 4.5,8.9-tetrahydroindanone [Formula (6)] In quartz f, 2-cyclobentenone 2.45' 2-trimethylsilyloxy Pour butadiene 11.45', seal the tube, and
React at 240'O for to43. After cooling the reactant,
By rectifying under reduced pressure, the target product 6-drimethylsilyloxytetrahydroindanone was obtained with a yield of 65%.
I got 1.

B, p,: 92-96'O/1.0~BgIRj liquid film): 1740.1655On-'NMR (CCI,):
δ4,70 (1/f, m), 0.19 (9#, s) Example 3 6-Medoxy 4.5.8.9. -tetrahydroindanone [formula (6)] and]6-n-butoxy4.5,8
．． 9.Production method of tetrahydroindanone [formula (6)] 2-cyclobentenone and 2-methoxybutadiene or 2-n-butoxybutadiene are reacted with the same substance as in Example 2, and the target product is obtained by rectification. 6-Medoxytetrahydroindanone (yield 68%, b, p, 80-88'
O10,5-11 g), or 6-'n-buto,
Xytetrahydroindanone (yield 62%, b, p, 8
2-90'O/0.1 rtanHg) was obtained.

Example 4 2.3-cis-2-formylmethyl-8-carboethoxymethyl-1-cyclopentanone [Formula 1 Formula % 6-nitoxytetrahydroindanone 10. A predetermined amount of ozone is passed through a 200d solution of methylene chloride at -70 to -78°C. Next, this reaction solution was mixed with zinc powder 51
．． Of acetic acid 130-added into a suspension solution of -10 to 4°
Perform the reduction reaction at C for 2 hours.

The reaction product was poured into water E2, extracted with methylene chloride, the organic layer was washed with heavy sodium chloride, washed with water, dried with sodium sulfate, and the solvent was removed.
By distilling the residue under reduced pressure, the target product 2.8-cis-
2-formylmethyl-8-carfoethoxymethyl-1-
9.62 cyclopentanone was obtained in a yield of 82.1 units.

B, p,: 66-68°O10,04HgIN (liquid film): 1741,1780.1722°-1 NMR (CCL, ):a9.85,4.10. L25 Example 2 2.8-cis-2-formylmethyl-3-carbotrimethylsilyloxymethyl-1-cyclopentanone [Formula (4
)] 6-Dolimethylsilyloxytetrahydroindanone 5.
A predetermined amount of ozone is passed into a methanol 1001 solution of Of at -70 to -78°C, and then 7Qml of dimethyl sulfide is added at -100 to 0°C and reacted for 2 hours.

By distilling the reaction product under pressure, the target product 2,3-
469 cis-2-formylmethyl-8-carbotrimethylsilyloxymethyl-1-cyclopentanone was obtained with a yield of 78%.

B,p,:140. -148°O/ 0.11EIII
HgIR (liquid film): l? 41,1780,1720-1 NMR (CCI, ): 9.85 (IH, s)
,0,15(9H,s) 4 Example 3 2.3-cis-2-phorbarmethyl-3-carbomethoxymethyl-1-cyclopentanone [Formula (4)] and]2
, 3-cis-2-phobalmethyl-3-carbo-n-butoxymethyl-1-cyclopentanone [2(4)] From 6-medoxytetrahydroindanone and 6-n-butoxytetrahydroindanone, 4, 1゜By the same operation as in Example 2, the target product 2,3-cis-2-formylmethyl-3-carbomethoxymethyl-1-cyclopentanone (
-Yield 85%, b, p, 112-114°O10,01
pharyngeal Hg) and 2,8-cis-2-phor is rumethyl-3-
Carbone-n-butoxymethyl-1-cyclopentanone (
Yield 7.4%, b, p, 186-140°O/0.0
05 Hg) f) X obtained.

Reference example 2-Shrimp-ethyl jasmonate [formula (2)] and] 2-
Ebijasmonate-n-butyl formula 1 Formula % Separately prepared from triphenyl n-propylphosphonium bromide in a well-dried, nitrogen-substituted container.
, 180 d of a dimethoxyethane solution of triphenyl n-propylphosphorane corresponding to 0.05 mol was added, and to this was added 10.11 mol of 2,3-cis-2-formylmethyl-
A solution of 8-carboethoxymethyl-1-cyclopentanone in 100ml of the same solvent was added dropwise, and the mixture was heated to 20ml in a room.
Let it react for a minute. After the reaction is complete, dilute hydrochloric acid is added to the reaction solution,
Extract with methylene chloride. After recovering the solvent, the residue was subjected to reduced pressure to obtain the desired ethyl 2-epi-jasmonate at a yield of 9.1% and 0.2%.

IRI liquid g) 1745.1653CIn-'NMR (C
CI4. ) 5.80-5.05 (,2H, m),
3, ss[H, q), 1.07 (8 1i, t ) boiling point 60''~65'O/0.15■H.

In the above example, 2,8-cis-2-formylmethyl-8
-2,8-cis-2-formylmethyl-8-carpol n-butoxymethyl-1-cyclopentanone obtained in Study Example 8 is used instead of carboethoxymethyl-1-cyclopentanone. The same procedure was followed except that n-butyl 2-shrimp jasmonate was obtained in a yield of 78%. boiling point 72°
~76°C10, OIWmH17° Reference Example S 2-Shrimp-trimethylsilyl jasmonate [te (2)]
Reference example for the production of 2.3-cis-phorylξ-methyl-8-carbotrimethylcutoxymethyl-
After reacting 1-cyclopentanone, sufficiently cooled water was added, extracted with methylene chloride, dried over magnesium sulfate, and rectified under reduced pressure to obtain trimethylsilyl 2-shrimp-jasmonate (yield 60%, b, p, 98
~96'O10, 2 category Bσ) is obtained.

Reference Example 8 Production method of methyl jasmonate 2-Shrimp - Dissolve 24 ml of ethyl jasmonate in 100 ml of anhydrous methanol 2, replace the inside of the container with nitrogen 2, add 10 ml of methanol containing 0.56 f of sodium methoxide, and heat for 8 hours. Reflux. The reaction solution was neutralized with dilute hydrochloric acid, extracted with methylene chloride, and the solvent was dried over magnesium sulfate.Then, the solvent was collected and rectified under reduced pressure to obtain the desired methyl jasmonate with a yield of 212. 9
Obtained at 2.3%.

JR (liquid film) 1741.1650i) 11-'NMR (
CCI4) 5.60-5.12 (2H, m), 4.
60 (8H, s), 2.52-1.88 (12H, m), i, o (aH, t) b, p, 92°010.02yaHg By the same 11M operation, trimethylsilyl 2-epi-jasmonate Methyl jasmonate is obtained in a yield of 82.4%, from n-butyl 2-epi-jasmonate in a yield of 80%, and from methyl 2-epi-jasmonate in a yield of 90%.

(1 other person)

Claims (1)

[Claims] 1. The following formula (6)▲There are mathematical formulas, chemical formulas, tables, etc.▼(
6) However, in the formula, R is a lower alkyl group or -SiR'_3 (here, R' represents a lower alkyl group)
A 6-substituted tetrahydroindanone represented by: 2. The following formula (7) ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (
7) 2-cyclopentenone represented by and the following formula (8) ▲
There are mathematical formulas, chemical formulas, tables, etc. ▼ (8) However, in the formula, R represents a lower alkyl group or -SiR'3 (here, R' represents a lower alkyl group). The following formula (6) ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (6) However, in the formula, R is a lower alkyl group or -SiR'_3 (here, R' represents a lower alkyl group)
A method for producing a 6-substituted tetrahydroindanone represented by