JPS6226248A - Cis-2-alkyl-3-alkoxycarbonylmethylcyclopentanol - Google Patents

Abstract

NEW MATERIAL:A cis-2-alkyl-3-alkoxycarbonylmethylcyclopentanol expressed by formula I (R1 represents 1-8C straight chain or branched alkyl; R2 represents methyl or ethyl). EXAMPLE:cis-2-Methyl-3-methyloxycarbonylmethyl-1-cyclopentanol. USE:Useful as an intermediate for synthesis of perfumes, from which a cis-2- alkyl-3-alkyloxycarbonylmethylcyclopentanone useful as a perfume substance having a superior fragrance can be synthesized in high purity without substantially containing a trans isomer. The compound is also useful as one component of a perfume composition. PREPARATION:A 2-alkyl-2-cyclopentene derivative expressed by formula II (X is Cl, etc.) is reacted with a compound expressed by formula III (R3 and R4 represent 1-4C alkyl), and the product is subjected to, for example, a decarboxylation reaction. The product is further subjected to hydroforation reaction in the presence of a borane, and oxidized to obtain the compound expressed by formula I.

Description

DETAILED DESCRIPTION OF THE INVENTION (a) Industrial application field The present invention is directed to a new substance, cis-2-
Relating to alkyl-3-alkoxycarbonylmethylcyclopentanol.

More specifically, the present invention provides the following formula (1) in which R1
represents a straight-chain or branched alkyl group of Cl-C8, and R2 represents a methyl group or an ethyl group.
Relating to alkyl-3-alkoxycarbonylmethylcyclopentanol. The above formula (1) compound is a cis-2-alkyl-3-alkyloxycarbonylmethylcyclopentanone represented by the following formula (A) useful as a fragrance substance, where R1 and R2 have the same meanings as above. Cis-methyl dihydrojasmone is an extremely useful compound as an intermediate that can be synthesized with high purity without substantially containing trans-integral components, and in particular, cis-methyldihydrojasmone is extremely important as a fragrance substance included in the above formula (A). 1.(In the above formula (A), R1
is a pentyl group and R is a methyl group). The compound of formula (1) is also useful as a component of a perfume composition.

(B) Prior art Compounds having a structure similar to the above formula (1) of the present invention include, for example, the following formula (B) described in JP-A-54-32457 σH where R and R' is an alkyl group, and R is cis and trans with respect to a hydroxyl group. A fragrance composition has been proposed that includes 2-alkyl-3-hydroxycyclopentyl acetate as one of the aroma-active ingredients. . Alternatively, the compound of formula (B) above (when R' is a methyl group) is subjected to an oxidation reaction to form the compound of formula (C
> υ However, in the formula, R has the same meaning as above, and it is mentioned that it can be converted to the corresponding trans-unitary ketone compound represented by.

(c) Problems to be solved by the invention The above formula (
A) The aroma of the compound is extremely superior to that of trans-integrated compounds. However, the product obtained from the above formula (B) compound through an oxidation step (the above formula (C)) is trans-integrated, and the cis-integrated product of the above formula (A
) compounds cannot be obtained selectively.

(d) Means for Solving the Problems The present inventors have conducted extensive research into a method for selectively synthesizing the cis monomer of the above formula (A), which has an excellent aroma that cannot be obtained with the above conventional proposals. I went.

As a result, in the following formula (1) described in the conventional literature, where R
1 represents a C1 to C8 linear or branched alkyl group, R2 represents a methyl group or an ethyl group, and is a new substance cis-2-alkyl-3-
Alkoxycarbonylcyclopentanol has the above formula (
It was discovered that this is a useful intermediate for selectively synthesizing the cis form of A). Furthermore, we discovered a method by which the compound of formula (1) above can be easily synthesized industrially, and succeeded in its synthesis.

According to the present invention, the following formula can be easily synthesized from 2-alkyl-2-cyclopentanon-1-one, where X is CI, Br, OAc, OR (wherein, R is a C1 to C4 alkyl group). 2-alkyl-2-cyclopentene derivative represented by the following formula (5), in which R1 represents a C1 to C8 linear or branched alkyl group; However, in the formula, R3 and R4 represent linear or branched alkyl groups of 01 to C4, which may be the same or different. A catalytic reaction is carried out in the presence or absence of phenylphosphine to form 2-alkyl-3-(1-alkoxycarbonylalkoxy carbonylmethyl)-1-cyclopentene is formed, and the compound of formula (3) is subjected to decarboxylation reaction, or after decarboxylation reaction, transesterification reaction, or saponification and decarboxylation reaction, and then esterification reaction to form the following formula (2 ) In the formula, R1 and R2 have the same meanings as above, and 2-alkyl-3-(alkoxycarbonylmethyl)
-1-cyclopentene is formed, the compound of formula (2) is hydroborated in the presence of borane, and then oxidized in the presence of an oxidizing agent to form the following formula (1), where R1 represents a straight chain or branched alkyl group of Cl-C8, R2 represents a methyl group or an ethyl group, and contains a trans monomer of cis-2-alkyl-3-alkoxycarbonylmethylcyclopentanol represented by It was found that it can be easily synthesized with high purity without any oxidation.

Further, the compound of formula (3) above can be hydroborated in the presence of a borane and then subjected to an oxidation reaction in the presence of an oxidizing agent to form the following formula (2), where R, R3 and R4 are Synonymous with the above, cis-2-alkyl-3-(1-alkoxycarbonylalkoxycarbonylmethyl)-1-cyclopentanol is subjected to decarboxylation, or after decarboxylation, transesterification, or saponification and decarboxylation. It has been found that the compound of formula (1) of the present invention can be easily synthesized with high purity by carrying out an esterification reaction after the carbonic acid reaction. Then, by oxidizing the novel compound of the formula (1), the above-mentioned production mode of the compound of the present invention, which was found to be able to selectively synthesize the cis-unit compound of the above-mentioned formula (A) with excellent aroma, was applied to the above-mentioned manufacturing method of the compound of the above-mentioned formula (1). 4) Compound and the above formula (A
) When shown in a reaction process diagram including a synthesis example of the compound, it can be expressed as follows, for example.

H (+) (A) The present invention will be explained in detail below according to the above process diagram.

In the above process diagram, the compound of formula (4) can be easily obtained by reducing an alkylcyclopentanone, which is easily available in the market, and which is easily synthesized, followed by an acetylation or halogenation process.

Specific examples of the compound of formula (4) include 1-chloro-2-methyl-2-cyclopentene, 1-chloro-2-
Ethyl-2-cyclopentene, 1-chloro-2-propyl-2-cyclopentene, 1-chloro-2-butyl-2
-Cyclopentene, 1-chloro-2-pentyl-2-cyclopentene, I-chloro-2-heptyl-2-cyclopentene, 1-chloro-2-octyl-2-cyclopentene, 1-chloro-2-isopropyl-2-cyclopentene , 1-bromo-2-methyl-2-cyclopentene,
]-Bromo-2-ethyl-2-cyclopentene, 1-bromo-2-butyl-2-cyclopentene, 1-bromo-
2-hexyl-2-cyclopentene, 1-bromo-2-
Octyl-2-cyclopentene, 1-acetyl-2-methyl-2-cyclopentene, 1-acetyl-2-ethyl-2-cyclopentene, 1-acetyl-2-propyl-
2-cyclopentene, 1-acetyl-2-butyl-cyclopentene, 1-acetyl-2-pentyl-2-cyclopentene, 1-acetyl-2-heptyl-2-cyclopentene, 1-acetyl-2-octyl-2-cyclopentene, 1-methoxy-2-methyl-2-cyclopentene, 1-methoxy-2-ethyl-2-cyclopentene, 1
-Methoxy-2-butyl-2-cyclopentene, 1-methoxy-2-pentyl-2-cyclopentene, 1-methoxy-2-hexyl-2-cyclopentene, 1-methoxy-2-octyl-2-cyclopentene, 1-ethoxy -2-methyl-2-cyclopentene, 1-ethoxy-2
-Ethyl-2-cyclopentene, 1-ethoxy-2-propyl-2-cyclopentene, 1-ethoxy-2-pentyl-2-cyclopentene, 1-ethoxy-2-hexyl-2-ctyl-2-cyclopentene, 1- Propoxy-2-methyl-2-cyclopentene, 1-propoxy-2-ethyl-2-cyclopentene, 1-propoxy-
2-butyl-2-cyclopentene, 1-propoxy-2
-pentyl-2-cyclopentene, 1-propoxy-2
-hebutyl-2-cyclopentene, 1-propoxy-2
-cutyl-2-cyclopentene, 1-butoxy-2-
Methyl-2-cyclopentene, 1-butoxy-2-ethyl-2-cyclopentene, 1-butoxy-2-propyl-2-cyclopentene, 1-butoxy-2-butyl-2
-cyclopentene, 1-butoxy-2-pentyl-2-
Examples include cyclopentene, 1-butoxy-2-hexyl-2-cyclopentene, 1-butoxy-2-hebutyl-2-cyclopentene, and 1-butoxy-2-octyl-2-cyclopentene.

From the above formula (4) compound to the following formula (3), where R1 represents a straight chain or branched alkyl group from C1 to C8, and R3 and R4 may be the same or different. To synthesize 2-alkyl-3-(1-alkoxycarbonylalkoxycarbonylmethyl)-1-cyclopentene, which represents a linear or branched alkyl group, for example, the compound of formula (4) and The dialkyl sodium malonate salt represented by the following formula (5), where R3 and R4 represent a Cl-C4 linear or branched alkyl group which may be the same or different, is dissolved in an organic solvent. (In the above formula (4), X is C
I and Br), or by reacting in the presence of a zero-valent palladium complex and triphenylphosphine (in the case of X is OAc or OR in the above formula (4)),
Can be easily synthesized.

Examples of the dialkylsodium malonate used in the above reaction include dimethylsodium malonate, diethylsodium malonate, dibrovirsodium malonate, dibutylsodium malonate, etc. be able to. The amount of these dialkylsodium malonate salts to be used is, for example, about 1 to about 1 per compound of formula (4).
A preferable example is a range of about 0 mol.

In addition, as the O-valent palladium complex used in the above reaction,
Examples include tetrakistriphenylphosphinepalladium and ethylenebistriphenylphosphinepalladium. The amount of these zero-valent palladium complexes to be used is, for example, about 0.00% relative to the compound of formula (4).
Preferred examples include a range of about 0.001 to about 0.01 mole. Also, the amount of triphenylphosphine to be used is, for example, about 0.05 to about 0.05 to about 0.01 mole, based on the compound of formula (4).
A preferable range is about 0.5 mol. Examples of organic solvents include ether, tetrahydrofuran, benzene, and toluene. The amount of these organic solvents to be used may be appropriately selected without any particular restrictions, but for example, a range of about 2 to about 20 times the weight of the compound of formula (4) is often adopted.

The above reaction can be easily carried out, for example, preferably at a temperature range of about 0° to about 80°C, and preferably for a reaction time of about 2 to about 20 hours. After the reaction is completed, it can be treated according to conventional methods and, if necessary, easily purified by means such as column chromatography or distillation.

For example, the formula (3
) Compounds include 2-methyl-3-(1-methoxycarbonylmethoxycarbonylmethyl)-1-cyclopentene, 2-methyl-3-(1-
ethoxylponyl(ethoxylponylmethyl)-1-
Cyclopentene, 2-methyl-3-(l-butoxycarbonylbutoxylponylmethyl)-1-cyclopentene, 2-ethyl-3-(1-methoxycarbonylmethoxycarbonylmethyl)-1-cyclopentene, 2-ethyl-3-(1 -ethoxylponylethoxylponylmethyl)-1-cyclopentene, 2-ethyl-3-(1
-proboxylic group (proboxyl group)
-1-cyclopentene, 2-ethyl-3-(1-butoxyluponylbutoxyluponylmethyl)-1-cyclopentene, 2-propyl-3-(1-methoxycarbonylmethoxycarbonylmethyl)-1-cyclopentene,
2-Propyl-3-(1-ethoxyluponylethoxyluponylmethyl)-1-cyclopentene, 2-propyl-3-(1-butoxyluponylbutoxyluponylmethyl)-1-cyclopentene, 2-pentyl-3- (
1-methoxycarbonylmethoxycarbonylmethyl)-
1-Cyclopentene, 2-pentyl-3-(1-ethoxyluponylethoxyluponylmethyl)-1-cyclopentene, 2-hexyl-3-(1-isoproboxyluponylisobroboxyluponylmethyl)-1-cyclopentene , 2-hexyl-3-(1-methoxycarbonylmethoxycarbonylmethyl)-1-cyclopentene, 2-octyl-3-(1-methoxycarbonylmethoxycarbonylmethyl)-1-cyclopentene, 2-octyl-3-( 1-isobutoxylponylisobutoxylponylmethyl)-1-cyclopentene, 2-pentyl-3-(l-methoxycarbonylt-butoxycarbonylmethyl)-1-cyclopentene, 2-ethyl-3-
(1-ethoxylponylmethoxylponylmethyl)
-1-cyclopentene, 2-pentyl-3-(1-ethoxyluponylmethoxyluponylmethyl)-1-cyclopentene, 2-hebutyl-3-(1-ethoxyluponylmethoxyluponylmethyl)-1-cyclopentene, etc. I can give an example.

The following formula (2) can be synthesized from the above formula (3) as described above. In the formula, R1 has the same meaning as above, R2 represents a methyl group or an ethyl group, and is represented by 2-alkyl- 3-(Alkoxycarbonylmethyl)-1-cyclopentene can be synthesized by, for example, a method in which the compound of formula (3) is subjected to a saponification and decarboxylation reaction followed by an esterification reaction, or a method in which a decarboxylation reaction is performed followed by a transesterification reaction. Alternatively, saponification and decarboxylation reactions that can be easily synthesized by employing any method such as a decarboxylation reaction method include, for example, sodium hydroxide, potassium hydroxide, barium hydroxide, calcium hydroxide, etc. This can be easily carried out in the presence of an alkali such as, if necessary, a solvent such as water, methanol, or ethanol. The reaction can be carried out, for example, preferably at a temperature range of about 20° to about 100°C, preferably for about 2 to about 20 hours. The amount of the alkali used in the reaction is preferably in the range of about 2 to about 4 moles based on the compound of formula (4). In addition, there are no particular restrictions on the amount of the solvent used, and it may be selected as appropriate.
For example, the amount may preferably range from about 2 to about 10 times the weight of the compound of formula (3). After the saponification and decarboxylation reaction, it may be neutralized with acids such as sulfuric acid, hydrochloric acid, and phosphoric acid according to a conventional method.

The esterification reaction can be easily carried out by a conventional method, for example, by reacting the product obtained above with methanol or ethanol in the presence of an acid catalyst such as phosphoric acid, sulfuric acid, or hydrochloric acid. This can be easily done. The reaction temperature and reaction time are, for example, about 2
Preferred examples include reaction conditions of about 0° to about 100°C for about 2 to about 20 hours. The amount of methanol and ethanol to be used can preferably range from, for example, about 5 to about 20 moles based on the compound of formula (3). Further, the amount of the acid catalyst to be used may be selected as appropriate, but for example, about 5 to 5
A preferable example is a range of about 20%.

After completion of the reaction, the compound of formula (2) can be easily obtained with good purity and yield by neutralization and washing treatment according to conventional methods, and purification by means such as distillation and column chromatography. Furthermore, instead of the esterification reaction described above, a reaction using diazomethane can also be employed.

Specific examples of compounds included in the compound of formula (2) that can be synthesized as described above include, for example, 2-
Methyl-3-methyloxycarbonylmethyl-1-cyclopentene, 2-methyl-3-ethyloxycarbonylmethyl-1-cyclopentene, 2-ethyl-3-methyloxycarbonylmethyl-1-cyclopentene, 2-ethyl-3-ethyl Oxycarbonyl-1-cyclopentene, 2-propyl-3-methyloxycarbonylmethyl-1-cyclopentene, 2-propyl-3-ethyloxycarbonylmethyl-1-cyclopentene, 2-butyl-3-methyloxycarbonylmethyl-1- Cyclopentene, 2-butyl-3ethyloxycarbonylmethyl-
1-cyclopentene, 2-benzene-3-methyloxycarbonylmethyl-1-cyclopentene, 2-benzene-3-ethyloxycarbonylmethyl-1-cyclopentene, 2-hexyl-3-methyloxycarbonylmethyl-1-cyclopentene, 2- Hexyl-3-ethyloxycarbonylmethyl-1-cyclopentene, 2-hebutyl-3-methyloxycarbonylmethyl-1-cyclopentene, 2-hebutyl-3-ethyloxycarbonylmethyl-1-cyclopentene, 2-octyl- Examples include 3-methyloxycarbonylmethyl-1-cyclopentene.

In addition, as another method for obtaining the compound of the above formula (2), the compound of the above formula (
3) The compound of formula (2) can also be easily obtained by decarboxylating the compound and then transesterifying the compound.

The above decarboxylation reaction is carried out using the compound of formula (3) in the presence of a salt such as sodium chloride, potassium chloride, or lithium chloride in a solvent such as water, dimethylformamide, dimethyl sulfoxide, etc. ! ′]l
It can be easily carried out at about 200°C to about 200°C. The amount of salts used in this reaction is preferably in the range of about 1 to about 10% by weight based on the compound of formula (3). Furthermore, there is no particular restriction on the amount of the organic solvent used, and it can be selected as appropriate;
For example, the amount may preferably range from about 1 to about 10 times the weight of the compound. After the reaction is completed, the product is isolated, and in the compound of formula (3), R3 or R
When 4 is other than a methyl or ethyl group, it can be converted into the compound of formula (2) by transesterification with methanol or ethanol in the presence of a base catalyst. The reaction is
For example, under reflux conditions of methanol or ethanol, about 0
．． This can easily be carried out at temperatures ranging from about 5 to about 2 hours. As the base catalyst, for example, sodium methylate, sodium ethylate, etc. can be preferably used.

The amount of these base catalysts to be used is, for example, about 0.00% relative to the compound of formula (3). A preferable example is a range from OI to about 0.1 mol. Further, the amount of ethanol or methanol to be used may range from about 5 to about 20 moles based on the compound of formula (3).
After the reaction is completed, the compound of formula (2) can be obtained with good purity and yield by carrying out the same method as described above. The reaction crude product can be purified by, for example, column chromatography, distillation, or the like.

From the compound of formula (2) that can be synthesized as described above, cis-2-alkyl-3 represented by the following formula (1)H of the present invention, where R1 and R2 have the same meanings as above, To synthesize -alkyloxycarbonylmethyl-1-cyclopentanol, the compound of formula (2) is mixed in an organic solvent, such as a borane tetrahydrofuran solution, a borane dimethyl sulfide solution,
Hydroboration in the presence of borane such as thexylborane and 9-borabicyclo(3,3,1)nonane,
This can be easily carried out by carrying out an oxidation reaction in the presence of an oxidizing agent.

The amount of borane to be used in the above hydroboration is, for example, about 0.
A preferable example is a range of about 4 to about 10 moles. Preferable examples of the organic solvent to be used include tetrahydrofuran, dimethoxyethane, and diglyme. The amount of these organic solvents to be used may be appropriately selected, and can be, for example, about 2 to about 20 times the amount of the compound of formula (2). Hydroboration is, for example, about -20 to about +2
At a reaction temperature of about 0°C, about 0. This can be easily carried out under preferred conditions in a range of about 1 to about 4 hours. After the reaction is completed, it is treated with an alkaline aqueous solution and the next oxidation reaction step is carried out. The oxidation reaction is carried out under preferred conditions, for example, in the presence of an oxidizing agent such as hydrogen peroxide, at a temperature range of about 0 to about 60°C, for about 0.5 to about 5 hours. It can be done easily. The amount of the oxidizing agent to be used is preferably in the range of, for example, about 1 to about 5 moles based on the above-mentioned hydroboration product. After the reaction is completed, neutralization and water washing are performed, and M! ! Thus, the compound of formula (1) can be easily obtained without substantially containing trans monomer.

If necessary, the crude product of the compound of formula (1) obtained as described above may be treated with an acid such as P-)luenesulfonic acid, phosphoric acid, hydrochloric acid, sulfuric acid, etc., and, for example, toluene, hexane, benzene. By carrying out a catalytic reaction in an organic solvent such as , xylene, etc., only the trans unit present in the crude product of the compound of formula (1) can be lactonized.

In this way, separation of cis-integrated and trans-integrated can be further facilitated. The amount of acid used in the above-mentioned catalytic reaction may be appropriately selected, and is preferably in the range of about 0.5 to about 10% by weight, based on the ff1u compound of formula (1). I can do it. Further, the amount of the organic solvent to be used may be appropriately selected, and may be, for example, about 1 to about 20 times the weight of the ¥fL product of the compound of formula (1). The catalytic reaction, for example,
0'' to about 200°C, for example, about 1 to about 200°C.
It can be preferably carried out under conditions of a reaction time of about 20 hours. After the reaction is completed, the compound is neutralized, washed with water, and purified by means such as column chromatography or distillation to obtain a pure compound of formula (1) containing substantially no trans components.

Specific examples of compounds included in the compound of formula (1) that can be obtained as described above include, for example, cis-2-
Methyl-3-methyloxycarbonylmethyl-1-cyclopentanol, cis-2-methyl-3-ethyloxycarbonylmethyl-1-cyclopentanol, cis-2
-ethyl-3=methyloxycarbonylmethyl-1-cyclopentanol, cis-2-ethyl-3-ethyloxycarbonylmethyl-1-cyclopentanol, cis-
2-propyl-3-methyloxycarbonylmethyl-1
-cyclopentanol, cis-2-propyl-3-ethyloxycarbonylmethyl-1-cyclopentanol,
cis-2-butyl-3-methyloxycarbonylmethyl-1-cyclopentanol, cis-2-butyl-3-ethyloxycarbonylmethyl-1-cyclopentanol, cis-2-pentyl-3-methyloxycarbonylmethyl -1-cyclopentanol, cis-2-pentyl-3-ethyloxycarbonylmethyl-1-cyclopentanol, cis-2-hexyl-3-methyloxycarbonylmethyl-1-cyclopentanol, cis-2-hexyl -3-ethyloxycarbonylmethyl-1-cyclopentanol, cis-2-hebutyl-3-methyloxycarbonylmethyl-1-cyclopentanol, cis-2
-hebutyl-3-ethyloxycarbonylmethyl-1-
Examples include cyclopentanol, cis-2-octyl-3-methyloxycarbonylmethyl-1-cyclopentanol, and cis-2-octyl-3-ethylexycarbonylmethyl-1-cyclopentanol.

In addition, in the above reaction process diagram, from the compound of formula (3) above to cis-2-alkyl-3 represented by the following formula (2)' H where R1, R3 and R4 have the same meanings as above. -(1-Alkoxycarbonylalkoxycarbonylmethyl)-1-cyclopentanol can be easily synthesized by hydroborating the above formula (3) and then subjecting it to an oxidation reaction. The reaction method is to hydroborate the above-mentioned compound of formula (2) and then oxidize it to produce the compound of formula (1), by the same method as described above to produce the compound of formula (2)'. Can be easily synthesized. Specific compounds included in the compound of formula (2)' that can be synthesized as described above include compounds of formula (3) described above, in which a hydroxyl group is introduced at the 1-position of the specifically mentioned compound. , and cis-type compounds in which the cyclopentene ring is saturated.

In order to synthesize the compound of formula (1) from the compound of formula (2)' which can be synthesized as described above, a method of subjecting the compound of formula (2)' to a saponification and decarboxylation reaction followed by an esterification reaction,
Or a method of carrying out a transesterification reaction after a decarboxylation reaction,
Alternatively, the 9 reaction method, which can be easily carried out by decarboxylation, is a reaction method in which the compound of formula (3) described above is converted to the compound of formula (3).
2) It can be synthesized with good yield and purity by performing the same method as the method for synthesizing the compound. As mentioned above, the compound of formula (1) obtained here can be purified by means such as chromatography or distillation, or it can be purified by contacting the compound of formula (1) with an acid to obtain a compound that substantially contains trans monomers. It is possible to obtain the compound of formula (1) with good purity without having to do so.

Embodiments of the present invention will be described in detail with reference to reference examples and examples below.

(E) Reference Example (1) Synthesis of 1-acetoxy-2-pentyl-2-cyclopentene, formula (4).

2-pentyl-2-cyclopenten-1-one 201g
(1,333 mol), 210 g of a 70% solution of sodium and sumethoxyethoxy hydride (0,
728 mol) was added dropwise. After the dropwise addition, the mixture was stirred at room temperature for 1 hour, and then the reaction mixture was poured into 1 kg of ice water and 350 ml of concentrated hydrochloric acid, the oil layer was separated, and the aqueous layer was further extracted with toluene. The organic layer was washed with soda ash, concentrated with an evaporator, and
Obtain 210 g of product. To this oil were added 750 ml of pyridine and 286 g of acetic anhydride, and the mixture was stirred at room temperature for 4 hours. after that,
Toluene was added to the reaction solution, which was washed with dilute hydrochloric acid II, then washed with water, an aqueous soda ash solution, and dried over magnesium sulfate to obtain 275 g of a crude product. This is distilled to a purity of 95
% or more of the title compound was obtained. Yield: 72% Boiling point: 83° to 84°C/3 mmHg (2) Synthesis of 1-acetoxy-2-propyl-2-cyclopentene, formula (4).

Instead of 2-pentyl-2-cyclopenten-1-one in Reference Example 1, 2-propyl-2-cyclopenten-1-
152 g of the title compound was obtained in the same manner as in Reference Example 1, except that 150 g of ion was used. Yield: 75%, boiling point:
71°-72°C/3mmHg.

(3) Synthesis of 1-acetoxy-2-octyl-2-cyclopentene, formula (4).

Instead of 2-pentyl-2-cyclopenten-1-one in Reference Example 1, 2-octyl-2-cyclopenten-1-
The same procedure as in Reference Example 1 was carried out using 71 g of 100% of the compound to obtain 73.2 g of the title compound. Yield: 84%, boiling point: 9
5"~97'C/3mmHg.

(4) Synthesis of 1-chloro-2-pentyl-2-cyclopentene, formula (4).

2-pentyl-2- to a mixture of 3.8 g lithium aluminum hydride and 500 ml dry ether
A mixture of 30 g (0.2 mol) of cyclopenten-1-one in 100 ml of dry ether is added dropwise at 3 DEG -8 DEG C. for 12 hours. After further stirring for 30 minutes at the same temperature, water was added in a conventional manner to remove the ether layer, which was dried and concentrated to obtain 30 g of crude alcohol. Boiling point 79'~80''C/12mmH
g-Next, 2.8 g of phosphorus trichloride and 50 ml of dry benzene were added to the reactor, and 1.6 g of pyridine (0,0
Next, a mixed solution of 7.7 g (0.05 mol) of the crude alcohol obtained above and 50 ml of benzene was added dropwise at 0°C to 59°C for 12 hours, and the mixture was further stirred at room temperature for 2 hours. , the benzene layer was taken and concentrated to give the title compound. Boiling point: 7° to 74'C/2mmHg.

(5) Synthesis of 1-bromo-2-pentyl-2-cyclopentene, formula (4).

The title compound was obtained in the same manner as in Reference Example (4) except that phosphorus tribromide was used in place of phosphorus trichloride in Reference Example (4).

Boiling point near 5° to 80°C 10.9 mm Hg 6 (6) Tables 1 and 2 show the results of the same tests as above for various other compounds included in the compound of formula (4)
Shown in 2.

Table-1
mh Chlor Propyl 65°~68°C/2m
mHg Brom Ethyl 76' ~ 79' C
/2mmJ Brom Hexyl 80@~86@C
/2mmh Brome Octyl 90@~98'
C10,4mmHg Table-2 X R2 boiling point acetoxy methyl 62' C/2.5mm)
Ig acetoxy hebutyl 94°C/3mmHg
Methoxy methyl 60°~61' C/2mm
Hg<g) Example (1) Synthesis of 2-pentyl-3-(l-methoxycarbonylmethoxycarbonylmethyl)-1-cyclopentene, formula (3).

105.6 g (0.8 mol) of dimethyl malonate was added to a mixture of 32 g (0.8 mol) of 60% sodium hydride and 600 ml of dry tetrahydrofuran at 30°C.
Add dropwise at 5°C for 13 hours. After dropping, heat at 55°C for 1
The mixture is heated for a certain period of time, and the inside of the reaction system is directly replaced with argon gas. In an argon atmosphere, 1-acetoxy-2-pentyl-2-cyclopentene 39.2 g (0.2 mol), triphenylphosphine 5.24 g (0.02 mol), tetrakistriphenylphosphine palladium (0 valence) 1.616
g (0.7 mmol) and dry tetrahydrofuran 1
A solution obtained by stirring 00ml at room temperature for 1.5 hours is added.

Thereafter, the mixture is heated and stirred at 58° to 60'C for 20 hours.

After the reaction is completed, the reaction solution is poured into cold water, extracted three times with ether, and the ether layer is washed twice with brine. It was dried over anhydrous magnesium sulfate, and the solvent was distilled off using an evaporator to obtain 101 g of a crude product. This was distilled under reduced pressure to obtain 49.7 g of the title compound. Boiling point: 119'~120''C1
0.5 mmHg, yield: 92.7%.

(2) Synthetic formula of 2-pentyl-3-(1-methyloxycarbonylt-butyloxycarbonylmethyl)-1-cyclopentene (3) In place of dimethyl malonate in Example (1), t-butylethyl malonate 182 .7g (
The same procedure as in Example 1 was conducted except that 0.59 mol) was used to obtain 58.2 g of the title compound. Yield: 95%.

(3) Synthesis of 2-propyl-3-(l-methoxycarbonylmethoxycarbonylmethyl)-1-cyclopentene, formula (3).

In place of 1-acetoxy-2-pentyl-2-cyclopentene in Example 1, 1-acetoxy-2-propyl-2
The same procedure as in Example 1 was carried out except that -cyclopentene was used to obtain 43.6 g of the title compound. Yield: 91.5%
, boiling point; 112° to 114° C10,6 mmHg.

(4) Synthesis of 2-pentyl-3-(1-methoxycarbonylmethoxycarbonylmethyl)-1-cyclopentene, formula (3).

12.0 g of 60% sodium hydride in 11 flasks
(0.3 mol) and 500 ml of dry tetrahydrofuran
46 g of dimethyl malonate was added dropwise over 30 minutes at 10''~15''C and stirred at room temperature for 30 minutes.Subsequently, 1-bromo-2-pentyl-2 was added at 10~18°C for i hours. - 21 g of cyclopentene and 100 ml of benzene
Add the solution dropwise, and heat and stir at 66°C for 4 hours. After cooling, pour into saturated ammonium chloride solution, extract with ether,
Concentrate after drying. 50 g of crude product are obtained. Purify by distillation under reduced pressure. Boiling point: 122”~125°C/lmmHg
.

(5) Similar results were obtained for various compounds included in the compound of formula (3) in accordance with the above method. The results are shown in Table-3.

Table-3 RI R3R4 (1) Methyl Methyl Methyl (2)
Ethyl Ethyl Methyl (3) Butyl Methyl Methyl (4) Pentyl
Ethyl Methyl Table-3 (5) Hexyl Methyl Methyl (6)
Hebutyl Ethyl Methyl (7) Octyl Methyl Methyl Boiling Point (1) 65° ~ 666C/2mmHg (2) 77°
~788C/2mmHg (3) 80"~82'C
/2mrnHg(4) 82°~84°C/1.5mm
Hg (6) 86°~87' C/1.0mmHg (7
) 112' ~ 119" C/2.2mmHg (6)
Synthesis of 2-pentyl-3-methoxycarbonylmethyl-1-cyclopentene, formula (2).

2-pentyl-3-(1-methoxycarbonylmethoxycarbonylmethyl)-1-cyclopentene 14g (0
, 052 mol), sodium chloride 4.1 g, water 3.8 g
, a mixture of 55 mm1 of dimethyl sulfoxide at 160°
Heat to ~170°C for 18 hours. After the reaction was completed, the mixture was extracted with ether and dried to obtain 11 g of a crude product. Distillation under reduced pressure yielded 8.46 g of the title compound. Yield: 77.2%, boiling point 81''-83'C/2mmHg.

(7) 2-propyl-3-methoxycarbonylmethyl-
Synthesis of 1-cyclopentene formula (2).

24 g of 2-propyl-3-(1-methoxycarbonylmethoxycarbonylmethyl)-1-cyclopentene (0,1 13.6 g of the title compound was obtained in the same manner as in Example 6, except that mol) was used. Boiling point: 69°~70@C/2mmH
g1 yield 75%.

(6) Synthesis of 2-pentyl-3-methoxycarbonyl-1-cyclopentene formula (2).

2-pentyl-3-(1-methoxycarbonylmethoxycarbonylmethyl)-1-cyclopentene 28.6g
(0.1 mol) in 50 ml of water and 50 ml of methanol
, and added to a solution of 12.4 g (0.22 mol) of potassium hydroxide, and heated and stirred at 70° to 80° C. for 12 hours. After the completion of cooling, the reaction solution was poured into 300 ml of 2NH2S04, extracted with ether, washed twice with water, and concentrated. The crude carboxylic acid was heated at 130°-140° C0 for 4 hours, followed by 200 ml methanol. ! A mixture of 2 ml of sulfuric acid and 8
After heating for an hour, after ether extraction, coarse! ! 17g of material was obtained. Purification by distillation yielded 14.49 g of the title compound. Yield: 69%.

(7) Synthesis of cis-2-pentyl-3-(1-methoxycarbonylmethoxycarbonylmethyl)-1-cyclopentanol Formula (2)′ In a reaction vessel, add 1 portion of tetrahydrofuran.
50ml, sodium borohydride 4.24g (0,
11 mol) and heated at 16° to 19”C under an argon atmosphere.
21.28 g of boron trifluoride ether complex is added dropwise over 110 minutes. Stir at the same temperature for 2 hours, add 2-pentyl-
26.8 g (0.1 mol) of 3-(1-methoxyluponylmethytoxyluponylmethyl)-1-cyclopentene was added dropwise at -0.5'' to 0'C over 15 minutes, and immediately after the dropwise addition, 35% filtration was achieved. A mixture of 40 ml of hydrogen oxide water, 806 g of sodium hydroxide, and 140 ml of water was heated at 0° to 30° Cl2.
Dropped in 0 minutes and reached 40°CT! Stir for 40 minutes. After extraction with ether, it was dried and concentrated to obtain 27 g of a crude product.

As a result of gas chromatography analysis of this product, it was found that the ratio of cis and nidolance was 4:1. This product was purified by silica gel column chroma (n-hexane: ethyl acetate = 5:1) to obtain 18.76 g of the pure title compound containing no trans monomer. Yield: 70%.

(8) Synthesis of cis-2-propyl-3-(1-methoxycarbonylmethoxycarbonylmethyl)--1-cyclopentanol, formula (2)'.

In the same manner as in Example (7), 2-propyl-3-(1
-methoxycarbonylmethoxycarbonylmethyl)-1
- React using 1.82 g (0.01 mol) of cyclopentene, 0.42 g of sodium borohydride, and 2013 g of boron trifluoride ether complex, and purify the obtained crude product with silica gel column chromatography to obtain trans 1.31 g of pure, free title compound were obtained.

(9) Synthesis of cis-2-pentyl-3-(1-ethoxycarbonyl-t-butoxycarbonylmethyl)-1-cyclopentanol formula (2)'.

34 g of 2-pentyl-3-(1-ethoxycarbonylt-butoxycarbonylmethyl)-1-cyclopentene,
(0.11 mol) in 120 ml of dry tetrahydrofuran
-5''~-46C for 5 minutes, add 15゜0ml of borane dimethyl sulfide solution and react at the same temperature for 1.6 hours.To this, 27.5ml of water and 52.5ml of 3N aqueous sodium hydroxide solution. , 20.5 m of 35% hydrogen peroxide
1 and react at 40°C for 1 hour. After completion, ether extraction was carried out, and after drying, the ether was distilled off and the crude product was reduced to 31.7
I got g. This was purified by silica gel chromatography to obtain 22.2 g of the pure title compound containing no trans monomer. Yield: 60%.

(10) Various compounds included in the compound of formula (2) were synthesized according to the method of Example (6). The results are shown in Table-4.

Table-4 RI R2 yield% 1 Methyl Methyl 78.82 Ethyl Methyl 80.53 Butyl
Methyl 76.34 Hexyl Methyl 72.45 Hebutyl Methyl
74.26 Octyl Methyl 69.
17 Methyl Ethyl 70.58
Ethyl Methyl 68.29 Propyl Ethyl 70.510 Butyl
Ethyl 68.811 Pentyl Ethyl 65.412 Hexyl Ethyl
69.413 Hebutyl ethyl
71,214 octyl ethyl
70.4(11) Synthesis of cis-2-pentyl-3-methoxycarbonylmethyl-1-cyclopentanol formula (1).

In a reaction vessel, 4.2 g (20 mol) of 2-pentyl-3-methoxycarbonylmethyl-1-cyclopentene was dissolved in 20 ml of dry tetrahydrofuran, and 2 ml (20 mmol) of borane dimethyl sulfide solution was heated at -5°C under an argon stream. Add with . React at the same temperature for 1.5 hours, then add 4.5 ml of water and 8.4 ml of 3N sodium hydroxide aqueous solution.
l, add 3.3 ml of 35% hydrogen peroxide solution, and add 3.3 ml of 35% hydrogen peroxide solution,
Stir at 506C for 1 hour. After completion, the mixture was extracted with ether, dried, and concentrated to obtain 4.70 g of a crude product.

Gas chromatography revealed that it was a mixture of 6:5 cis-nidorans. This crude product was purified by silica gel column chromatography to obtain 2.7 tLg of a pure cis-unit title compound containing no trans-unit. Boiling point; 129'-130'C/2mmHg-yield;
65%.

(12) Cis-2-propyl-3-methoxycarbonylmethyl-1-cyclobetanol formula % Formula % 2-propyl- instead of 2-pentyl-3-methoxycarbonylmethyl-1-cyclopentene in Example (11)
3-methoxycarbonylmethyl-1-cyclopentene 1
．． Example (11) except that 8 g (0.01 mol) was used.
) to obtain 980 mg of pure title compound. Boiling point: 121°-122'C/2mmHg, yield: 54%.

(]3) Synthesis of cis-2-pentyl-3-methoxycarbonylmethyl-1-cyclopentanol formula (1).

cis-2-pentyl-3-(1-methoxycarbonylmethoxycarbonylmethyl)-1-cyclopentanol 1
0.1g (0,036 mol), sodium chloride 3.6
Dissolve 3.3 g of water in 102 g of dimethyl sulfoxide and heat at 170° to 1800C for 18 hours. After the end,
After extracting ether, drying, and distilling off the ether, the crude! ! Thing 9
．． 4g was obtained. This ffl! ! Distill things under reduced pressure,
6.73 pure title compound containing no trans monomers
I got g. Yield: 66%.

(14) Cis-2-propyl-methoxycarbonylmethyl-1-cyclopentanol Formula % Formula % Cis-2-propyl-3-(1-methoxycarbonylmethoxycarbonylmethyl) -1-Cyclopentanol 2.56g (0,
01 mol), the pure title compound containing no trans monomer was obtained.

(15) Synthesis of cis-2-pentyl-3-ethoxycarbonylmethyl-1-cyclopentanol formula (1).

1.21 g (3.7 mol) of cis-2-pentyl-3-(1-ethoxycarbonylmethyl t-butoxycarbonylmethyl)-1-cyclopentanol was mixed with 5 ml of dimethyl sulfoxide, 0.36 g of sodium chloride, and 0.33 g of water.
g and heated at 182°C for 16 hours. After completion, ether extraction was performed and the ether was concentrated to obtain 810 mg.

To this was added 20 ml of 163% sodium methoxide-methanol solution, stirred at room temperature for 1.5 hours, extracted with ether, and after drying, the ether was distilled off to obtain 792 mg of a crude product. This was purified by silica gel column chromatography to obtain 630 mg of the pure title compound containing no trans monomer.

(16) Using the various compounds of formula (2) obtained above as raw materials, compounds included in the compound of formula (1) were prepared in Example (1).
It was synthesized according to 1). The results are shown in Table-5.

1 methj1 methyl )07
@C/2mmHg 41%2 1 til MethiIL R09@C/2.5m
m) Ig 44X Table-5 RI R2-trillion A1 Yield 3
Butyl Methi+1 +26 °C/1.
5mmHg 61X4 to 1shi II
Methyl 129-131°C/1.5m
m) Ig 72$5 hebutyl methyl
115 ~ 116' C10,5mm) Ig
7H6 octyl methyl 119 ~+20
” C10.5mmH880%7 Methyl
Methi II 119 ~ 120' C/
2mmt1g 49$8 Ethyl Ethyl 119 ~ 121 @ C/2) 1g
49χ9 Prohil Ethyl 122
~1239C/1.9mm) Ig 53Xl
O Butyl Ethyl 128 ~ 129 °
C/1.5mm) Ig 6H:11 Heni, Shin Un 119 ° C10,8m
m) 18 75$12 Hebutyl Ethyl 125 ~ 127” C/1.0mmH8
74%13 1') fn Methyl 130
~132' C10,8mmHg 81%
Reference Example (7) Cis-2-pentyl-3-methoxycarbonylmethyl-1-cyclopentanone Formula % Formula % 2.43 g of cis-2-pentyl-3-methoxycarbonyl-1-cyclopentanol was dissolved in 180 ml of ether. , 2N dichromic acid solution (sodium dichromate 20.2
g,i! ! Add water to 26.32g of sulfuric acid (98%) and add 10
Set it to 0m1. ) 26° (7 ml) and stir at 5° to 10°C for 6 minutes. After adding isopropanol, aqueous sodium bicarbonate was added, and after filtration, the organic layer was separated, dried, and reduced to obtain 2.2 g of a crude product. This was purified by silica gel chromatography to obtain 1.91 g of the title compound. Analysis of this by gas chromatography showed that it had a purity of 99% or more. Boiling point: 115°C/2mmHg*Yield: 78
%.

(8) Cis-2-propyl-3-methoxycarbonylmethyl-1-cyclopentanone formula % Formula % Cis-2-propyl-3-methoxycarbonylmethyl-1-cyclo Using 1.09 g of pentanone, 760 mg of the title compound with a purity of 99% or more was obtained. Boiling point: 109 ° C 1 Yield 6
9%.

(f) Effects of the Invention The following formula (1) of the present invention, where R1 and R2 have the same meanings as above, and cis-2-alkyl-3-alkoxycarbonylmethylcyclopentanol is The novel compound described below is a compound of the following formula (A), which is useful as a fragrance superior in aroma compared to a trans monomer by oxidizing the compound of the formula (1). However, in the formula, R1 and R2 are , as defined above, is a compound useful as an intermediate that can synthesize cis-2-alkyl-3-alkyloxycarbonylmethylcyclopentanone with high purity without substantially containing trans-integral components.

In particular, as a fragrance that includes the above formula (A), the extremely important cis-methyl dihydrojasmonate (formula (A)
It is a compound useful as a synthetic intermediate in the case where R1 is a pentyl group and R2 is a methyl group.

Therefore, the present invention can provide an intermediate useful for producing the above-mentioned compound of formula (A) which is substantially free of trans-units, which could not be obtained conventionally.

Patent applicant Hasegawa Perfume Co., Ltd. - Agent
Person Patent attorney Hiraiki Odajima - 1 person other than J

Claims (1)

[Claims] 1. The following formula (1) ▲There are mathematical formulas, chemical formulas, tables, etc.▼ (1) However, in the formula, R1 represents a C1 to C8 linear or branched alkyl group, and R2 is Cis-2-alkyl-3-alkoxycarbonylmethylcyclopentanol, which represents a methyl group or an ethyl group.