JPH0710865A - New delta-lactone and its production - Google Patents

Abstract

PURPOSE:To obtain a new compound useful, e.g. as synthetic intermediate for a perfume, etc. CONSTITUTION:A compound of formula I (R is a 1-10C hydrocarbon), e.g. 5- hydroxy-trans-5-heptenoic acid-delta-lactone. Further, the compound of formula I is obtained by reacting a compound of formula II with an organic peracid, e.g. peroxyformic acid or hydrogen peroxide in an organic acid, e.g. acetic acid in the presence of an organic acid salt of formula III (R is a 1-4C hydrocarbon; M is alkali metal) e.g. sodium propionate.

Description

Detailed Description of the Invention

[0001]

INDUSTRIAL APPLICABILITY The present invention is useful as a fragrance, various synthetic raw materials or intermediates, and in particular, a novel lactone useful as a synthetic intermediate lactone of various insect pheromones and an optically active δ-lactone important in the perfume industry. And its manufacturing method.

[0002]

2. Description of the Related Art Conventionally, many methods are known for producing an optically active δ-lactone. As the synthesis method, 1) a method using an optically active N, N-dibutylnorefedrine as a starting material [Chem. Letters, 843
(1988)], 2) A method for synthesizing δ-keto acid by reduction with yeast [Journal of Synthetic Organic Chemistry, 49, 37, (19).
91)], 3) a method of optically resolving a racemate using an enzyme [Tetra. Letters, 28, 5367,
(1987)] and the like are known.

[0003]

However, in the method using an optically active compound as a starting material, an expensive reagent must be used, the number of steps is large, and the operation is complicated. Further, in the method using yeast reduction, the substrate concentration must be lowered to carry out the reaction, resulting in poor efficiency and complicated purification. Furthermore, the method of optically resolving with an enzyme requires an equivalent amount of an optically active substance, and has problems such as poor resolving efficiency. An object of the present invention is to provide a novel lactone which is useful as a starting material or the like in the production of an optically active δ-lactone and a method for producing the same, which can solve the above-mentioned drawbacks of the conventional method.

[0004]

The present invention has the general formula

[0005]

[Chemical 5]

A novel δ-lactone compound represented by the formula (wherein R represents a hydrocarbon group of 1 to 10) and a general formula

[0007]

[Chemical 6]

A compound represented by the formula (wherein R represents a hydrocarbon group of 1 to 10) and an organic peracid or hydrogen peroxide in an organic acid of the general formula

[0009]

[Chemical 7]

## STR1 ## wherein R is a hydrocarbon group having 1 to 4 carbon atoms and M is an alkali metal; It is a method for producing the δ-lactone compound shown.

The lactone represented by the above-mentioned general formula [I] (hereinafter referred to as 5-hydroxy-5-alkenoic acid-δ-lactone), which is a compound of the present invention, is a novel compound and, as will be described later, is asymmetrically hydrogenated. With high yield and high optical activity δ
-Can be converted to a lactone.

R in the above general formula [I] has 1 to 10 carbon atoms.
The above hydrocarbon group may be essentially any, but a linear or branched saturated or unsaturated aliphatic hydrocarbon group is usually preferable. Specific examples of 5-hydroxy-5-alkenoic acid-δ-lactone [I] include 5-hydroxy-5-heptenoic acid-δ-lactone, 5-hydroxy-5-octenoic acid-δ-lactone and 5-hydroxy-. 5-nonenoic acid-
δ-lactone, 5-hydroxy-5-decenoic acid-δ-lactone, 5-hydroxy-5-undecenoic acid-δ-lactone, 5-hydroxy-5-dodecenoic acid-δ-lactone, 5-hydroxy-5-tridecene Acid-δ-lactone, 5-hydroxy-5-tetradecenoic acid-δ-lactone, 5-hydroxy-5-pentadecenoic acid-δ-lactone, 5-hydroxy-5-hexadecenoic acid-δ-lactone, 5-hydroxy-7 -Methyl-5-octenoic acid-δ
-Lactone, 5-hydroxy-8-methyl-5-nonenoic acid-δ-lactone, 5-hydroxy-9-methyl-5-
Examples thereof include decenoic acid-δ-lactone, 5-hydroxy-10-methyl-5-undecenoic acid-δ-lactone and 5-hydroxy-11-methyl-5-dodecenoic acid-δ-lactone.

The general formula [I] used in the above-mentioned production method of the present invention is
Specific examples of the compound represented by [I] (hereinafter referred to as 2-alkylidenecyclopentanone) include 2-ethylidenecyclopentanone, 2-propylidenecyclopentanone, 2-pentylidenecyclopentanone, and 2-pentylidene. Cyclopentanone, 2-hexylidene cyclopentanone, 2-heptylidene cyclopentanone, 2-octylidene cyclopentanone, 2-nonylidene cyclopentanone, 2-decylidene cyclopentanone, 2-undecyl Dencyclopentanone, 2-isobutylidenecyclopentanone, 2-isopentylidenecyclopentanone, 2-
Examples thereof include isohexylidene cyclopentanone, 2-isoheptylidene cyclopentanone, and 2-isooctylidene cyclopentanone. These are, for example, known methods [Chem. Pharm. Bull. 21
(1), 215 (1973)] and the like to condense cyclopentanone with various aldehydes to generally synthesize a mixture of cis and trans isomers. These isomers can be easily separated by means such as fractional distillation or column chromatography, but the cis isomer, trans isomer or an arbitrary mixture thereof can be used in the reaction.

Specific examples of the organic peracid include formic acid, peracetic acid, perpropionic acid, perbutanoic acid, perpentanoic acid, m-chloroperbenzoic acid, perbenzoic acid and trifluoroperacetic acid. The amount of organic peracid or hydrogen peroxide used is 0.5 to 3 mol, preferably 0.6 to 1.5 mol, based on 5-hydroxy-5-alkenoic acid-δ-lactone [I]. To be

Specific examples of the organic acid include acetic acid, propionic acid, butanoic acid, pentanoic acid and the like. Organic acid salt [II
Specific examples of [I] include sodium acetate, potassium acetate,
Examples thereof include potassium propionate, sodium propionate, sodium butanoate, potassium butanoate and the like.
When using the organic acid salt, it is advantageous to use it in the state of a saturated solution of the organic acid in terms of operability and reaction. The amount of the organic acid salt [III] used is usually 0.5 to 0.5 with respect to the organic peracid.
It is preferably 4 mol, particularly 1.0 to 2.0 mol.

The reaction temperature is usually 10 to 80 ° C., especially 20 to
A range of 55 ° C is preferred. The reaction time is appropriately selected depending on the reaction temperature, the raw materials used, etc., but is generally about 0.5 to 5 hours. Isolation and purification of the reaction product can be carried out by a unit operation known per se such as neutralization, extraction, distillation and column chromatography.

5-hydroxy-obtained according to the invention
The 5-alkenoic acid-δ-lactone [I] is easily induced to the optically active δ-lactone [IV] by the asymmetric hydrogenation with the asymmetric complex catalyst shown below.

[0018]

[Chemical 8]

(In the formula, * represents an asymmetric carbon and R represents the above meaning.) As is well known, an asymmetric complex catalyst used for asymmetric hydrogenation generally includes a metal such as ruthenium or rhodium. Is formed by coordinating an asymmetric phosphorus ligand. Specific examples of the asymmetric complex catalyst containing ruthenium as a metal center include HRuCl (TBPC) ₂ and H ₂ Ru (T
BPC) ₂ [TBPC = trans-1,2-bis (triphenylphosphinomethyl) cyclobutane], Ru ₂
X ₄ (DIOP) ₃ , RuHCl (DIOP) ₂ [X =
Cl, Br; DIOP = 2,2-dimethyl-1,3-dioxolane-4,5-bis (methylene) bis (diphenylphosphine)], RuCl ₂ (BPPM), RuH
₂ (BPPM) ₂ [BPPM = N- (butoxycarbonyl) -4-[(diphenylphosphino) methyl] pyrrolidine, RuCl ₂ (BPPFA) [BPPFA = N,
N-dimethyl [1- (2- (diphenylphosphino)]
Ferrocenyl] ethyl] amine, Ru ₂ Cl ₂ (Chi
raphos) ₂ [chiraphos = bis (diphenylphosphino) butane], Ru ₂ Cl ₄ (BINA)
P) ₂ NEt ₃ , RuHCl (BINAP) ₂ , [BI
NAP = 2,2-bis (diphenylphosphino)-
1,1'-binaphthyl] and the like.

The asymmetric complex catalyst containing rhodium as the central metal is classified into two types, neutral and cationic. Since the neutral one is generally unstable to air, it is prepared without isolation in the vessel used for the asymmetric hydrogenation reaction. A specific example is [RhCl (DIOP)] (Benz
en), [RhCl (BPPM)] (THF) and the like. Since the cationic one is relatively stable to air, it can be isolated, but it can also be used for the asymmetric hydrogenation reaction without isolation. A specific example is [Rh (COD) (DIOP)] ClO.
₄ [COD = 1,5-cyclooctadiene], [Rh
(COD) (DPPM)] ClO ₄ , [Rh (COD)
(Chiraphos)] ClO ₄ , [Rh (NBD)]
(DIOP)] ClO ₄ [NBD = norbornadiene], [Rh (NBD) (BINAP)] BF _{4 and the} like.

These asymmetric complex catalysts such as those described in J. C
hem. Sco. Chem. Commun. , 922
(1985), J. Organomet. Chem. ，
It is easily prepared by the reaction of a ruthenium or rhodium halide derivative with various asymmetric phosphorus ligands according to the method described in 370 319 (1989) and the like. When using, either one kind of enantiomer is used. The amount of catalyst used is 5-
Hydroxyl-5-alkenoic acid- [delta] -lactone [I] is 1/10 to 1/5000 times mol, and the reaction solvent is methylene chloride, chloroform, dichloroethane or other halogenated hydrocarbon, diethyl ether, tetrahydrofuran, dioxane, dimethoxy. Examples thereof include ether solvents such as ethane, aromatic hydrocarbons such as benzene, toluene, xylene, and an arbitrary mixed solvent thereof. The reaction can usually be carried out under a hydrogen atmosphere of 1 to 150 Kg / cm ² under conditions of 10 to 150 ° C. Isolation and purification of the reaction product can be carried out by a unit operation known per se such as distillation or column chromatography.

[0022]

EFFECTS OF THE INVENTION If 5-hydroxy-5-alkenoic acid-δ-lactone [I] found by the present inventors is utilized, the optically active δ can be obtained by a simple operation from a raw material which is cheaper and easier to obtain than the conventional method. -Lactone [IV] can be produced in good yield. Other 5-hydroxy-5-alkenoic acid-δ
-Lactone [I] is widely useful as a synthetic raw material.

[0023]

EXAMPLES The present invention will be specifically described below with reference to examples.

Example 1 Saturated potassium acetate acetic acid solution 13.9 ml, trans-2
-Ethylidene cyclopentanone 1.50 g (13.6 m
mol) and 40% peracetic acid 2.39 g (1
2.6 mmol) was added dropwise at 30 ° C. over 5 minutes. After reacting at the same temperature for 1 hour, 14 ml of water was added and toluene 50 m
Extracted twice with 1. Toluene solution is 10% saline solution 10
ml, 5% aqueous sodium sulfite solution 10 ml, and 10% saline solution 10 ml in this order. An oily substance was obtained by drying over magnesium sulfate and recovering the solvent. 0.88 g of this was purified with hexane / ethyl acetate using {2/1 (volume ratio)} as a developing solvent and a silica gel column.
A colorless oily substance (yield 51%) was obtained. The analysis results of this oily substance were as follows.

[0025]

[Table 1]

From the above analytical values, it was confirmed that the product was 5-hydroxy-trans-5-heptenoic acid-δ-lactone.

Example 2 5.0 ml of saturated potassium acetate acetic acid solution, trans-2-
Pentylidene cyclopentanone 1.01 g (6.64 m
mol) and 40% peracetic acid 1.16 g with stirring
(6.10 mmol) was added dropwise at 32 ° C. over 10 minutes.
After reacting for 1 hour at the same temperature, 3.8 ml of water was added and the mixture was extracted twice with 25 ml of toluene. Toluene solution is 10% saline solution 5 ml, 5% sodium sulfite aqueous solution 5 ml, 10%
It was washed in order with 5 ml of a% sodium chloride solution. An oily substance was obtained by drying over magnesium sulfate and recovering the solvent. This was purified with hexane / ethyl acetate {3/1 (volume ratio)} as a developing solvent and purified using a silica gel column to give 0.64.
g (57% yield) of a colorless oily substance was obtained. The analysis results of this oily substance were as follows.

[0028]

[Table 2]

From the above analytical values, it was confirmed that the product was 5-hydroxy-trans-5-decenoic acid-δ-lactone.

Example 3 7.7 ml of saturated potassium acetate acetic acid solution, 1.55 g (10.2 mmo) of cis-2-pentylidenecyclopentanone
1) was charged, and 1.78 g (9.3%) of 40% peracetic acid was added with stirring.
6 mmol) was added dropwise at 28 ° C over 12 minutes. 1 at the same temperature
After reacting for 4 hours, 4.1 ml of water was added and toluene 25 m
Extracted twice with 1. Toluene solution 10% saline solution 5m
1, 5% aqueous sodium sulfite solution (5 ml) and 10% sodium chloride solution (5 ml) were washed in this order. Dried over magnesium sulfate,
An oily substance was obtained by collecting the solvent. This was purified with hexane / ethyl acetate using {4/1 (volume ratio)} as a developing solvent and purified using a silica gel column to obtain 0.93 g (yield 54%) of a colorless oily substance. The analysis results of this oily substance were as follows.

[0031]

[Table 3]

From the above analytical values, it was confirmed that the product was 5-hydroxy-cis-5-decenoic acid-δ-lactone.

Example 4 7.2 ml of saturated potassium acetate acetic acid solution, trans-2-
Heptylidene cyclopentanone 1.50 g (8.33 m
mol) and charged with stirring, 40% peracetic acid 1.42 g
(7.49 mmol) was added dropwise at 28 ° C. for 10 minutes.
After reacting at the same temperature for 1 hour, 8 ml of water was added to toluene 5
Extracted twice with 0 ml. Toluene solution is 10% saline solution 10 ml, 5% sodium sulfite aqueous solution 10 ml, 10%
It was washed in order with 10 ml of a% sodium chloride solution. An oily substance was obtained by drying over magnesium sulfate and recovering the solvent.
This was purified with hexane / ethyl acetate {2/1 (volume ratio)} as a developing solvent and purified using a silica gel column to give 0.9.
5 g (58% yield) of a colorless oily substance was obtained. The analysis results of this oily substance were as follows.

[0034]

[Table 4]

From the above analytical values, it was confirmed that the product was 5-hydroxy-trans-5-dodecenoic acid-δ-lactone.

Example 5 11.3 ml of saturated potassium acetate acetic acid solution, trans-2
-3.00 g of undecylidene cyclopentanone (12.
7 mmol) and 40% peracetic acid 2.24 g under stirring
(11.78 mmol) was added dropwise at 30 ° C. over 5 minutes.
After reacting at the same temperature for 1 hour, 14 ml of water was added and the mixture was extracted twice with 50 ml of toluene. Toluene solution is 10% saline solution 10 ml, 5% sodium sulfite aqueous solution 10 ml, 1
It was washed in order with 10 ml of 0% saline solution. An oily substance was obtained by drying over magnesium sulfate and recovering the solvent. This was purified with hexane / ethyl acetate using {2/1 (volume ratio)} as a developing solvent and purified using a silica gel column to obtain 1.86 g (yield 58%) of a colorless oily substance.
The analysis results of this oily substance were as follows.

[0037]

[Table 5]

From the above analytical values, it was confirmed that the product was 5-hydroxy-trans-5-hexadecenoic acid-δ-lactone.

Reference Example 1 Preparation Example of 5 (R) -Pentyl-δ-valerolactone In a 50 ml autoclave, 130 mg (0.773) of 5-hydroxy-trans-5-decenoic acid-δ-lactone was added.
mmol), Ru ₂ Cl ₄ [(+)-DIOP] ₃ 1
4.3 mg (0.007733 mmol) and 10 ml of tetrahydrofuran were added under a nitrogen stream, and the hydrogen pressure was 50 kg /
Hydrogenation was carried out at 50 cm ² for 45 hours. An oily substance was obtained by collecting the solvent. This was purified with hexane / ethyl acetate {2/1 (volume ratio)} as a developing solvent and purified using a silica gel column to obtain 108 mg {[α] D = + 3.
7.93 ° (c = 1.25, MeOH) (yield 82
%)} Oily substance was obtained. IR, MS, 1H of this substance
-NMR analysis revealed that it was consistent with the authentic product, 5-pentyl-δ-valerolactone. Optical purity is known as pure 5
Specific rotation of (R) -pentyl-δ-valerolactone {T
etra. Letters, 29, 1915, (198
8)} was determined to be 63% ee.

Reference Example 2 Preparation Example of 5 (S) -Pentyl-δ-valerolactone In a 50 ml autoclave, 350 mg (2.08 m) of 5-hydroxy-trans-5-decenoic acid-δ-lactone was added.
mol), Ru ₂ Cl ₄ [(+)-BINAP] ₂ NE
t ₃ 16.8 mg (0.01 mmol) and tetrahydrofuran 6 ml were added under a nitrogen stream, and the hydrogen pressure was 100 kg /
It was performed cm ^2, 60 hours hydrogenated at 50 ° C.. An oily substance was obtained by collecting the solvent. This was purified with hexane / ethyl acetate using {2/1 (volume ratio)} as a developing solvent and purified using a silica gel column to obtain 333 mg {[α] D = -5.
4.69 ° (c = 1.15, MeOH) (yield 94
%)} Oily substance was obtained. IR, MS, 1H of this substance
-NMR analysis revealed that it was consistent with the authentic product, 5-pentyl-δ-valerolactone. Optical purity is known as pure 5
Specific rotation of (S) -pentyl-δ-valerolactone {T
etra. Letters, 29, 1915, (198
It was determined to be 91% ee by comparing 8)}.

Reference Example 3 Preparation Example of 5 (S) -Pentyl-δ-valerolactone 5-hydroxy-cis-5 was added to a 50 ml autoclave.
-Decenoic acid-δ-lactone 347 mg (2.07 mmo
l), Ru ₂ Cl ₄ [(+)-BINAP] ₂ NEt ₃
16.8 mg (0.01 mmol) and 6 ml of tetrahydrofuran were added under a nitrogen stream, and the hydrogen pressure was 100 kg / cm.
² , hydrogenation was carried out at 50 ° C. for 60 hours. An oily substance was obtained by collecting the solvent. This was purified with hexane / ethyl acetate using {2/1 (volume ratio)} as a developing solvent and purified using a silica gel column to obtain 327 mg {[α] D = −55.
An oily substance at 14 ° (c = 1.19, MeOH) (yield 93%) was obtained. IR, MS, 1H-NMR of this substance
Was confirmed to be in agreement with the authentic product, 5-pentyl-δ-valerolactone. Specific optical rotation of known pure 5 (S) -pentyl-δ-valerolactone with optical purity {Tetra.
It was determined to be 92% ee by comparing Letters, 29, 1915, (1988)}.

Reference Example 4 Preparation Example of 5 (S) -heptyl-δ-valerolactone 10 ml of tetrahydrofuran was added to a 50 ml autoclave.
g, [RhCl (COD)] ₂ 3.8 mg (0.00
765 mmol), (−)-BPPM 9.3 mg
(0.0169 mol) was added under a nitrogen stream, and the mixture was stirred at room temperature for 1 hour to prepare [RhCl (−) BPPM)] (THF). 5-hydroxy-trans-5-dodecenoic acid-
298 mg (1.52 mmol) of δ-lactone was added under a nitrogen stream, and hydrogenation was carried out at a hydrogen pressure of 50 kg / cm ² and 50 ° C. for 45 hours. An oily substance was obtained by collecting the solvent. This was purified with hexane / ethyl acetate using {2/1 (volume ratio)} as a developing solvent and purified using a silica gel column to give 218 mg {[α] D = -26.19 ° (c = 1.2.
9, MeOH) (yield 73%)} was obtained as an oily substance. The IR, MS, and 1H-NMR analyzes of this substance were consistent with the authentic product, 5-heptyl-δ-valerolactone. Specific optical rotation of pure 5 (S) -heptyl-δ-valerolactone of known optical purity {Tetra. Letters, 2
9, 1915, (1988)} by comparing
It was determined to be 4% ee.

Claims (2)

[Claims] 1. A general formula: (In the formula, R represents a hydrocarbon group of 1 to 10). 2. A general formula: (Wherein R represents a hydrocarbon group of 1 to 10) and an organic peracid or hydrogen peroxide in an organic acid represented by the general formula: (Wherein R represents a hydrocarbon group having 1 to 4 carbon atoms and M represents an alkali metal), and the reaction is carried out in the presence of an organic acid salt represented by the general formula: (In the formula, R represents a hydrocarbon group of 1 to 10).