JPS606951B2 - Lactone production method - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a new method for producing lactone compounds of formula (1), which are useful in the perfumery field, with good selectivity and good yields.

The oxidative lactonization reaction for forming the compound of formula (1) from the compound of formula (b) of the present invention is a conventionally known reaction. The lactone represented by the following formula (1), which is the object of the method of the present invention, is a known compound and has a musk-like, civet-like, or amber-like odor, and can be added to a fragrance composition as an active ingredient. For example, it can be used as an aroma modifier that significantly improves the aroma.

1,15-bentadecanolide (exaltolide), which is one of the target compounds of formula (1) of the present invention, is a known substance isolated from angelica oil.

Hitherto, various general methods have been proposed for producing the lactone of formula (1).

For example, “Snake r.Patent, 727051 (195
2)", according to the following formula, and "Help.Ch
im. Acta. Q h8, 1087Z0 (1935)
According to ``According to the following formula, furthermore, ``J.AmChe
m. Soc. 587 654 (1936), further according to the following formula,
．． , 80, 129 (1947)'', the following formula,
We are currently synthesizing lactones according to the following.

In the above conventional method, the synthesis of the starting material cycloalkanone, -oxycarboxylic acid or -bromocarboxylic acid has the disadvantage that it requires a large number of steps, making it difficult and complicated to control the operation and reaction conditions, and being expensive. be.

In addition, the lactonization reaction operation is very complicated, and the selectivity and yield are poor, and furthermore, it is necessary to use a large dilution method, or to perform an additional depolymerization operation to form polyester. These disadvantages make it unsuitable for industrial implementation. The present inventors have conducted research in order to overcome the disadvantages and deficiencies of the conventional methods described above and to provide a method for industrially advantageous production of the lactone of formula (1) with excellent selectivity and good yield. As a result, the following formula (W), HO-CH2
-(C ratio) n-CH2-OH Formula (W) However, in the formula, n
is an integer of 5 to 2Q, preferably 8 to 16, and is a relatively easy-to-manipulate -dihydroxyalkane of Q, represented by the following formula (m), where R, , R2 and R3 are each the same or Recycled from the trisubstituted alkyl tin halide produced in an easy-to-handle and subsequent oxidative lactonization reaction, which may be different and represents a C, to C8 straight-chain or branched alkyl group. The resulting bis(trisubstituted alkyl*s) oxide is reacted to stannylate the following formula (0), where n, R,, R2 and R3
It has been discovered that Q, -di(trisubstituted alkyl staniloyloxy) alkanes represented by are as defined above, and can be easily produced in almost quantitative high yields.

Furthermore, this formula (0)Q, di(trisubstituted alkyl staniloyloxy)alkane can be broken into the lactone compound of formula (1) by simply contacting it with an active halogen in a previously unknown reaction mode. It has been discovered that oxidative lactonization can be carried out advantageously with selectivity and good yields.

Therefore, an object of the present invention is to provide an industrially advantageous method for producing the lactone of the formula (1) compound by easy means, with high purity and high yield.

Next, the method of the present invention will be explained in more detail, and many other objects and advantages of the present invention will become clearer from the following description.

The Q,w-dihydroxyalkane of the formula (W) compound used in the production of the starting material formula (0) compound of the present invention can be easily synthesized by total reduction of the corresponding Q, -dicarboxylic acid.

Specific examples of the compound of formula (W) include 1,
7-dihydroxyheptane, 1,8-dihydroxyoctane, 1,9-dihydroxy/nan, 1,10-dihydroxydecane, 1,11-dihydroxyundecane, 1
, 12-dihydroxydodecane, 1,13-dihydroxytridecane, 1,14-dihydroxytetradecane,
1,15-dihydroxybentadecane, 1,16-dihydroxyhexadecane, 1,17-dihydroxyheptadecane, 1,18-dihydroxyoctadecane, 1,1
9-dihydroxynonadecane, 1,20-dihydroxyeicosane, 1,21-dihydroxyheneicosane,
Examples include 1,22-dihydroxydocosane. Q, -dihydroxyalkane of formula (W) compound can be converted to Q, -dihydroxyalkane, which is the raw material compound of formula (0) of the present invention, by reacting with bis(trisubstituted alkyltin) oxide of formula (m) compound. The substituted alkylstannyloxy)alkanes are selectively converted to alkanes in good yields.

This stannylation reaction can be carried out, for example, by adding Q, Yamaichi dihydroxyalkane of formula (W) and bis(trisubstituted alkyltin) oxide of formula (m) into an inert organic solvent, and then adding it to an inert organic solvent, and then adding it to an inert organic solvent and adding it to a bis(trisubstituted alkyltin) oxide of formula (m). It can be carried out. The reaction temperature can be, for example, about 60°C to about 180°C, preferably about 8020°C to about 140°C. Examples of the bis(trisubstituted alkyltin) oxide of formula (m) to be used include bis(trimethyltin) oxide, bis(triethyltin) oxide, bis(tri-n-propyltin) oxide, bis(triisopropyltin oxide), Bis(tri-n-butyltin) oxide, bis(tri-isobutyltin) oxide, bis(tri-sec-butyltin) oxide, bis(tri-butyltin) oxide,
tert-butyltin) oxide, bis(tri-n-amyltin) oxide, bis(triisoamyltin) oxide, bis(tri-secondary amyltin) oxide, pis(tri-n-hexyltin) oxide, bis(tri-n-amyltin) oxide -octyltin) oxide, bis(ethyldimethyltin)oxide, bis(n-propyldimethyltin)oxide,
Bis(n-butyldimethyltin) oxide, bis(n-amyldimethyltin) oxide, pis(n-hexyldimethyltin) oxide, bis(n-octyldimethyltin) oxide, bis(methyldiethyltin) oxide,
Bis(n-propyldiethyltin)oxide, bis(n-propyldiethyltin)oxide,
-butyldiethyltin) oxide, bis(n-hexyldiethyltin) oxide, bis(n-octyldiethyltin) oxide, bis(methyldi-n-propyltin)
oxide, bis(ethyl di-n-propyltin) oxide, bis(n-butyldi-n-propyltin) oxide, pis(n-hexyldi-n-propyltin) oxide, bis(methyl di-n-butyltin) oxide, bis(
Ethyl di-m-butyltin) oxide, Pis(n-propyldi-n-butyltin) oxide, Bis(n-hexyldi-n-butyltin) oxide, Pis(methyldi-n-butyltin) oxide
-amyltin) oxide, bis(ethyldi-n-amyltin) oxide, bis(methyldi-n-hexyltin)
oxide, bis(ethyl-n-hexyltin) oxide, bis(methylethyl-n-propyltin) oxide, bis(methylethylisopropyltin) oxide, bis(methylethyl-n-butyltin) oxide, pis(
Examples include ethyl-n-propyl-n-butyltin) oxide, bis(methyl-n-hexyltin) oxide, and bis(methyl-n-butyl-n-octyltin) oxide.

These bis(trisubstituted alkyltin) oxide formulas (m)
The amount used is about 1 to about 5 per mole of the compound of formula (W).
A mole amount is sufficient, and preferably about 1 to about 2 moles are employed.

As the inert solvent used in the above stannylation reaction, any organic solvent inert to the reaction components and products can be used, such as "n-hexane, n-hebutane, n-
Octane, isooctane, petroleum ether, cyclohexane, benzene, toluene, xylene, etc. may be mentioned. These solvents may be used alone or in a mixture of two or more. There is no particular restriction on the amount of solvent used, but generally, a weight range of about 1 to about 10, preferably about 5 to about 5, is most commonly used for the compound of formula (W). Ru. After the completion of the stanylation reaction, the inert solvent used from the reaction system is concentrated under normal pressure or reduced pressure to obtain a good yield and purity of the raw material formula (D) used in the present invention. Substituted alkylstannyloxy) alkanes can be obtained. Since the compound of formula (m) obtained as described above has good purity, it can be used as it is in the next oxidative lactonization reaction without the need for any particular purification operation. Specific compounds of the -di(trisubstituted alkylstannyloxy) alkanes of the above formula (b) Nobi, used in the method of the present invention include, for example, bis(trisubstituted alkylstannyloxy)alkanes of the above formula (m). ) 1 containing each trisubstituted alkyltin group listed as a specific compound of oxide,
7-di(trisubstituted alkylstaniloyloxy)hebutane, 1,
8-di(trisubstituted alkylstannyloxy)octane, 1,
9-di(trisubstituted alkylstannyloxy)nonane, 1,1
0-di(trisubstituted alkylstannyloxy)decane, 1,1
i-di(trisubstituted alkylstannyloxy)undecane, 1
, 12-di(trisubstituted alkylstannyloxy)dodecane,
1,13-di(tri-substituted alkyl stannyloxy)tridecane, 1,14-di(mitakafusuma alkyl stannyloxy)tetradecane, 1,15-di(tri-substituted alkyl stannyloxy)pentadecane 1,17-di(trisubstituted alkylstaniloxy)heptadecane, 1,18-di(trisubstituted alkylstaniloxy)octadecane, 1,19-di(trisubstituted alkylstaniloxy)heptadecane, (roxy)nonadecane, 1,20-di(trisubstituted alkylstannyloxy)eicosane, 1,21
-di(trisubstituted alkylstannyloxy)heneicosan,
Examples include 1,22-di(trisubstituted alkylstannyloxy)docosan. The object of the present invention is the formula (1
) The lactone compound is obtained by oxidative lactonization of Q of the formula (b), -di(trisubstituted alkyl staniloyloxy)alkane by contacting it with an active halogen, with good yield and excellent selectivity. Can be done.

This oxidative lactonization reaction can be carried out, for example, by forming an active halogen in a reaction system with Q, -di(trisubstituted alkyl stanilooxy)alkane of formula (0) in a solvent inert to the reaction. - Add the haloacylamide at the same time, or add the N-haloacylamide in the solvent, into which the formula (
b) The reaction can be carried out by adding the compound in any order such as dropwise addition. The reaction temperature is, for example, about 0 to
The characteristic advantage of this oxidative lactonization reaction is that it can be carried out in a wide temperature range of about 150 qo, but can be carried out in a mild temperature range of about 10 to about 80 qo. In this oxidative lactonization reaction, the desired formula (
1) In addition to the compound, trisubstituted alkyl tin halides and acylamides are produced quantitatively.

The trisubstituted alkyltin halide can be converted into the bis(trisubstituted alkyltin) oxide used in the stannylation reaction by alkali treatment, and the acylamide can be converted into the N used in the oxidative lactonization reaction of the present invention by the action of halogen. Another characteristic advantage of the present invention is that it can be converted into a haloacylamide and there is no waste of the reagent used. In addition to the above-mentioned preferred embodiments, the oxidative lactonization reaction of a compound of formula (b) according to the novel reaction mode of the present invention can be carried out using an active halogen and a compound of formula (n).
This can be done by any means that can bring the compound into contact.

Here, the active halogen is halogen formed in the reaction system as shown in the above preferred embodiment. Formula (b) is not limited to gen atoms.
It includes all forms of halogen atoms that can be brought into contact with a compound in the form of a halogen atom. For example, it may be supplied to the reaction system in the form of an amide and a halogen, or it may be supplied as a halogen in the presence of light or in the presence of a radical initiator, or any other modification may be selected. . Examples of the N-haloacylamide used in the preferred embodiment of the oxidative lactonization reaction include N-monochloroacetamide, N-monobromoacetamide,
N-monoiodoacetamide, N-monochloropropionic acid amide, N-monobromopropionic acid amide, N-
Monoodopropionic acid amide, N-monochlorobutyric acid amide, N-monobromobutyric acid amide, N-monoodobutyric acid amide, N-chlorosuccinimide, N-bromosuccinimide, N-iodosuccinimide, N-chlorophthalic acid imide, N-bromphthalic acid imide, N-iodophthalimide, and the like. The amount of these N-haloacylamides used is based on the raw material formula (b) compound 1.
About 2 to about 10 mol, preferably about 2 mol
~about 4 mol is most commonly employed. Examples of solvents inert to the reaction used in the oxidative lactonization reaction include dichloromethane, chloroform, carbon tetrachloride, dichloroethane, n-pentane, n-hexane, petroleum hexane, n-hebutane, n- Octane, isooctane, cyclohexane, benzene, etc. may be mentioned.

These solvents are preferably in a dry state, and may be used alone or in a mixture of two or more. There are no special restrictions on the amount of solvent used, but usually the formula of the raw material (U
) About 1 to about 50 times the weight of the compound, preferably about 10 to about 200 times the weight of the compound.
After the completion of the oxidative lactonization reaction, if the target compound of formula (1) is dissolved in the reaction system, remove the precipitated acylamide in a furnace, concentrate the solvent from the furnace solution, and then The trisubstituted alkyltin halide was separated by distillation under reduced pressure, and the formula of the target lactone (
1) A compound can be obtained.

On the other hand, if the target compound of formula (1) is precipitated as a crystal in the reaction system, it is separated from the trisubstituted alkyltin halide solution by filtration, the crystal is dissolved in an appropriate solvent, and the acyl amide is prepared. The target lactone formula (1) is obtained in good yield and purity by washing with alkaline water to remove it, further washing with water if desired, drying with trinitrate, and concentrating the solvent.
compound can be obtained. Furthermore, if desired, in order to remove a small amount of oligomer produced as a by-product during this oxidative lactonization reaction, purification can be carried out by distillation under reduced pressure or column chromatography. In addition, this oligomer can be converted into the target compound of formula (1) with good yield by heat in the presence of a depolymerization catalyst, so almost all of the oxidation reaction product is converted into the target compound of formula (1) without wastage. It also has the advantage of being Specific examples of the compound of formula (1), which is the final target product of the present invention obtained by the above oxidative lactonization reaction, include 1,7-heptalide, 1
, 8-octaride, 1,9-nonalide, 1,10-decanolide, 1,11-undecanolide, 1,12
Dodecanolide, 1,13-tridecanolide, 1,
14-tetradecanolide, 1,15-pentadecanolide (exaltolide), 1,16-hexadecanolide (dihydroambrectolide), 1,17-hebutadecanolide, 1,18-octade-force Noride, 1
, 19-nonadecanolide, 1,20-eicosanolide, 1,21-heneicosanolide, 1,22-docosanolide, and the like.

The present invention will be explained in more detail below using reference examples and examples.

Reference Example 1 Production of 1,12-di(triethylstannyloxy)dodecane 1,12-dihydroxydodecane 10.1 and bis(
21.4 hours of triethyltin oxide was added to 100% penzene, a water separation device was attached, and the mixture was refluxed for 8 hours.

When the produced water is separated, it is approximately 1.8' of the theoretical amount. By concentrating benzene from the reaction system under reduced pressure, crude 1,12-di(triethylstannyloxy)dodecane 30
．． Get 0 nights. IR (liquid film method) of the crude product shows no absorption of hydroxyl groups (raw material), so the yield is quantitative.
This crude product is used in the next oxidation reaction without purification. Reference Example 2 Production of 1,15-di(tri-n-butylstannyloxy)pentadecane 1,15-dihydroxybentadecane 12
．． 2 and bis(tri-n-butyltin) oxide 35.
By adding 7 ml of water to 240 ml of toluene, attaching a water separation azeotrope, and refluxing for 1 hour, approximately the theoretical amount of 1.8 ml of water can be fractionated.

Next, toluene is concentrated from the reaction system under reduced pressure to obtain 45.0 g of crude 1,15-di(tri-n-butylstannyloxy)pentadecane in a quantitative yield.

Example 1 Production of 1,12-dodecanolide Tetrachlorination of 24.0 liters of the crude 1,12-di(triethylstannyloxy)dodecane obtained in Reference Example 1 and 11.0 liters of N-monobromoacetamide with 500 ml of In addition to carbon,
At 30 qo, I reacted in a 1-year period.

The crystals precipitated in the reaction system are collected in a furnace. Add 50% of chloroform to the crystalline substance, wash with saturated sodium bicarbonate water, then wash with water, dry with bamboo salt, combine the chloroform layer with the carbon tetrachloride layer of the furnace solution obtained earlier, concentrate the solvent, and remove the crude product. thing 1,1
32.3 hours of a mixture of 2-dodecanolide and triethyltin bromide are obtained. By distilling the mixture obtained here under reduced pressure, 23.0 units of triethyltin bromide and 3.3 units of 1,12 dodecanolide can be obtained. The yield of the obtained 1,12 dodecanolide was 41%.
and the standard substance, boiling point, refractive index, GLC, TLC, m
and NMR were all consistent. Also, distillation pot residue 4.5
The IR and NM rudders match the standard substance and are the target oligomer. Example 2 Production of 1,15-pentadecanolide (exaltolide) Crude 1 obtained in Reference Example 2
, 15-di(tri-n-butylstannyloxy)pentadecane 28.1 was dissolved in 300% dry n-hexane (Molecular Sieves 3A), and N-promusuccinimide 12 was dissolved under water cooling to maintain a concentration of 25q0. .9 Add gradually.

After that, it reacted for 2 hours at 25qo. Concentrating n-hexane from the reaction mixture, dissolving the obtained slurry in chloroform over 200 ships, washing with saturated sodium bicarbonate water, washing with water, drying with ramie, and concentrating the chloroform to obtain 1 of the target product. , 15-bentadecanolide and tri-n-butyltin bromide. Furthermore, by distilling under reduced pressure, tri-n-butyltin bromide 2
6.0 units and 5.8 units of 1,15-bentadecanolide (yield 69%) were separated. The 1,15-bentadecanolide obtained here has a refractive index, boiling point, GLC, T
LC, IR and NM old matched. In addition, distillation residue 2.5
The IR and NMR spectra also matched with the standard material, indicating that it was an oligomer of the target product. Example 3 Production of 1,14-tetradecanolide 11.1 hours of crude 1,14-di(trimethylstanyloxy)tetradecane produced in the same manner as in Reference Example 1 and 7.5 hours of N-chlorosuccinimide were added. The mixture was added to 100 ml of dry benzene and reacted for 8 hours under refluxing benzene.

After cooling, the benzene layer of the reactant was washed with saturated sodium bicarbonate water,
After washing with water and drying with bitter nitrogen, concentrate the benzene. The concentrate was distilled under reduced pressure to yield 3.8 g of trimethyltin chloride and 2.72 g of the target product, 1,14-tetradecanolide (yield: 60
%). The 1,14-tetradecanolide obtained here has a standard substance, refractive index, boiling point, GLC, TLC, IR.
The and NMR agree, and the distillation residue is 1.6, which is the oligomer of the target product. Example 4 Production of 1,16-hexadecanolide (dihydroamprettolide) 16.7 hours of crude 1,16-di(tri-n-butylstannyloxy)hexadecane produced in the same manner as in Reference Example 2 A solution of 200% dry carbon tetrachloride and 9.0% N-bromosuccinimide
It was added dropwise to a solution of 600% dry carbon tetrachloride at room temperature over a period of 4 hours.

Thereafter, the reaction is carried out for one specific period at room temperature. The crystals precipitated in the reaction system were collected in a furnace, and the crystals were dissolved in 50% of chloroform.
Dissolve in solution, wash with saturated sodium bicarbonate solution, wash with water, dry with bitter nitrogen, and combine with carbon tetrachloride layer. By concentrating the carbon tetrachloride-chloroform layer and distilling the concentrate under reduced pressure, the tree n
14.1 units of -butyltin bromide and 3.79 units of the target product 1,16-hexadecanolide (yield 73%) were obtained. The 1,16-hexadecanolide obtained here matched the standard substance in refractive index, boiling point, GLC, TLC, IR, and NMR. Distillation residue 1.2 days also standard material and IR and NMR
match and are the target oligomers. Example 5 Production of 1,18-octadecanolide Crude 1,18-di(methyldiethylstanyloxy)octadecane 13.4% produced in the same manner as Reference Example 2 and N-monoodopropionic acid Amido 15.4 evenings 100
The mixture was added to dry chloroform and reacted at 6030 for 8 hours.

After cooling, the chloroform layer of the reaction product was washed with saturated sodium bicarbonate water, then washed with water, dried with sulfur salt, and concentrated. The concentrate was distilled under reduced pressure to yield 12.0 g of methyl diethyltin iodide and 2.0 g of methyl diethyltin iodide. The target product, 1,18-octadecanolide, was obtained in 9 days (yield 52%).
The MR results showed that the distillation residue 2.3 was the desired oligomer. Example 6 Preparation of 1,13-tridecanolide Crude 1, obtained in the same manner as Reference Example 1, was added to a solution of N-bromphthalimide 11.3 days in 100% dry petroleum ether.
13-di(triethylstannyloxy)tridecane 12.
A solution of 200% dry petroleum ether was added dropwise at 45° C. over a period of 2 hours.

Thereafter, the Takaazusa reaction was carried out at the same temperature for 6 hours. After the reaction is completed, the petroleum ether is concentrated, the concentrate is dissolved in benzene 100, washed with saturated sodium chloride, washed with water, dried with young sulfur, and concentrated. The concentrate was distilled under reduced pressure to obtain 11.2 hours of triethyltin bromide and 3.0 hours (yield: 70%) of the target product, 1,13-tridecanolide. The boiling point, GLC, TLC, IR, and NMR of the obtained 1,13-tridecanolide matched those of the standard substance. Example 7 Production of 1,10-decanolide Crude 1,10-di(tri-propylstanyloxy)decane 13.4% and N-
5.6 units of monochloroacetamide was added to 50 °C of dichloromethane and reacted at 20 °C for 2 hours.

Claims (1)

[Claims] 1 The following formula (II), ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ However, in the formula, R_1, R_2, and R_3 may be the same or different, and represent a linear chain of C_1 to C_8 or α,ω-di(trisubstituted alkyl stannyloxy), which represents a branched alkyl group, and n is an integer from 5 to 20.
There are formulas (I), ▲mathematical formulas, chemical formulas, tables, etc. below, which are characterized by bringing an alkane into contact with an active halogen, where n has the same meaning as in formula (II). .