JPS59104339A - Preparation of 2,15-hexadecanedione - Google Patents

Abstract

PURPOSE:To obtain the titled compound useful as an intermediate for preparing muscone easily in high yield from an easily available starting material, by reacting a tetradecanedioic acid as the starting material with a chlorinating agent, and reacting the resultant reaction product with halogenomethylzinc. CONSTITUTION:A tetradecanedioic acid obtained by the fermentation method of a hydrocarbon corresponding to n-tetradecane, etc. with a microoranism is reacted with a chlorinating agent, preferably SOCl2, in an equimolar amount or more at 20-50 deg.C for 3-4hr to give a reaction product, which is then distilled under reduced pressure, etc. to remove the chlorinating agent and form a tetradecanedioyl chloride of formula I . The resultant tetradecanedioyl chloride of formula I is then reacted with a halogenomethylzinc of formula II (y is a real number expressed by <0<x<=2; X is F, Cl or Br) or a pseudohalogenomethylzinc of formula III (X is halogenoid, e.g. -CN, -NC, -OCN, -NCO, -SCN, -NCS, -CNO or -N3, etc.) in an organic solvent at -180-+100 deg.C to afford the aimed compound.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention provides 2,1 which is an intermediate for the production of muscone.
The present invention relates to a method for producing 5-hexadecanedione.

Muscone is a natural fragrant ingredient collected from the gonads of male shrews, and has long been well known as a high-class fragrance. However, it is unethical to kill muscone deer and collect natural muscone (1) from a conservation point of view, and it is becoming very difficult to obtain natural muscone. Regarding the synthesis of muscone. Several methods have been studied in the past, but a technology has been developed that allows for the synthesis of muscone from 2,15-hexadecanedione in a high yield (approximately 65%) (Japanese Patent Laid-Open No. 85536/1983). 2.1
5-hexadecanedione has attracted attention as an intermediate in the synthesis of muscone.

Conventionally, methods for synthesizing 2,15-hexadecanedione include (1) a method in which 8-ketononanoate is condensed by Kolbe electrolysis (Japanese Patent Publication No. 16708/1983), and (2+ butadiene dimer is condensed by the Wallaker method). Method of condensation after oxidation [Tsuji et al., Bull, Chem, Sue, Japa
n.

■+21, 547 (1978)), (31 Method of exclusive use from polythionyl CH, Wynberg+e
taJL J-A, C, S-+ 82+1447 (
1960) '] and (4) levulinic acid ester 2
- A method of synthesizing from a ketal compound and 1,6-9 sulfone (% Patent Publication No. 42648/1983) has been proposed.

However, the above method requires the use of an expensive platinum electrode in Kolbe electrolysis, and also requires Kolbe electrolysis of levulinic acid and adianoic acid to obtain the raw material ketononanoic acid. Kolbe electrolysis with low rate f:
Since it is used in two stages, it has drawbacks such as a significantly low overall yield.

In addition, method (2) requires 5 reaction steps even if Kolbe electrolysis is used for condensation, and 9 steps if condensation is performed by Grignard reaction, and the yield is low. There are drawbacks.

Furthermore, methods (2) and (4) have drawbacks such as difficulty in obtaining raw materials such as politizanyl or levulinic acid, a large number of reaction steps, and low yields. .

That is, all of these known methods have problems in industrial implementation, such as relatively complicated manufacturing processes, difficulty in obtaining starting materials, or low yields. .

In view of the above-mentioned situation, the present inventors focused on the fact that in recent years, long-chain dicarboxylic acids such as tetradecanedioic acid can be easily produced from the corresponding hydrocarbons (e.g., n-tetradecane) by fermentation methods. However, the present invention was accomplished based on the finding that 2,15-hexadecanedione can be easily produced from an easily available starting material by using the above-mentioned tetradecanedioic acid as a starting material.

The present invention will be explained in detail below.

The present invention is characterized in that, after converting tetradecanedioic acid into tetradecanedioyl chloride using a chlorinating agent, this is then reacted with methylzinc halide or pseudomethylzinc halide.

The tetradecanedioic acid used as a starting material in the present invention is n-
Tetradecane (this hydrocarbon can be extracted from petroleum using monoculacisol) can be obtained by fermentation using microorganisms capable of producing the corresponding long-chain dicarbonate from hydrocarbons (for example, −
(See Publication No. 29994). By reacting this tetradecanedioic acid with a chlorinating agent, tetradecanedioyl chloride can be easily excised. Chlorinating agents used to prepare tetradecanedioyl chloride from tetradecanedioic acid include phosphorus pentachloride, phosphorus trichloride, sulfolyl chloride,
Examples include thionyl chloride, but in the present invention,
It is also preferable to use thionyl chloride because it is easy to reduce the amount of chlorinating agent after the reaction is completed.

This reaction progresses relatively easily by stirring tetradecanedioic acid with the same or more mole of chlorinating agent at a temperature of 20 to 50°C for 3 to 4 hours. Further, the reaction may be carried out in an organic solvent inert to the chlorinating agent such as hentane, toluene, xylene, etc., but a solvent is not necessarily required.

From the reaction product thus obtained, the chlorinating agent is removed, for example using a vacuum distillation operation.

Next, in the present invention, the methylzinc halogenide and pseudomethylzinc halide used to react with this tetradecanedioyl chloride have a composition represented by the following formula (I).

Methylzinc halide: <Ck13)'1ZnX2-y (I) (where y is a real number expressed as g < x≦2, and X is 1
゛, c, g, Br or C2) pseudomethylzinc halide: (in the formula, y is a real number represented by Q (x≦2, x4
is -CN, -NC, -0eN, -NCOl-8CN,
-NC8°-CNO, -N, etc.) These methylzinc halides and pseudomethylzinc halogenides can be produced according to a method known as a method for preparing a B-aise reagent. For example, it can be produced by reacting methyl 10genide, such as methyl iodide and methyl bromide, with zinc powder to which copper has been added to the surface or an alloy of zinc and copper in a stone medium. At this time, when the reaction is carried out in a polar solvent, methylzinc halide is obtained as a simple substance, but in a non-polar solvent, it is produced in the form of an associated compound. Although dimethylzinc and zinc halide are reacted, methylzinc halide can also be obtained by reacting methylmagnesium halide with zinc halide. Sisoidal methylzinc halide can also be easily produced as E4 in the same manner as above.

Tetradecanedioyl chloride and ha0/7' in the present invention
Reactions with methyl lead halides or pseudomethyl lead halides can be performed with organic solvents such as hydrocarbons such as hexane, benzene, toluene; ethers such as ethyl ether, detrahydrofuran, mexane; Ketones such as acetone, methyl ethyl ketone, and anisole;
Esters such as ethyl acetate; or halogenated hydrocarbons such as carbon tetrachloride, chloroporum, chlorobenzene, or mixtures thereof. The concentration of tetradecanedioyl chloride in this reaction is preferably 50% by weight or less; if this concentration is too high, side reactions may occur.

The reaction temperature is -80'C to ioo°C, especially =3
0°C to 30°C is preferred. If the reaction temperature is too low, the reaction rate will be slow, and if the temperature is too high, side reactions will occur.

The amount of needles of methylzinc halogenide or cisoidal methylzinc halide used in the above reaction is preferably 2 to 10 times the mole of tetradecanedioyl chloride, and if the above amount is less than 2 times the mole of tetradecanedioyl chloride. If the unreacted tetradecanedioyl chloride is E-<, the half-baked acid of the reaction, 14-oxopentadecanoyl chloride, will remain, resulting in a low reaction efficiency. come to arise.

After the reaction is completed, the reaction solution is washed with acid and alkali to remove the solvent, and the resulting solid content is recrystallized using methanol to obtain pure 2,15-hexadecanedione as white crystals.

Incidentally, muscone is synthesized from 2,15-hexadecanedione by performing intramolecular aldol condensation of 2,15-hexadecanedione to form a monkey, and then converting 2,15-hexadecanedione into a monkey using a known method. This can be done by hydrogenation in the presence of a radium catalyst. For example, 2,15-hexadecanedione can be mixed with a tertiary aluminum compound such as 1 ↓9 of a neutral aluminum phenoxy in the presence of an inert solvent such as hexane, benzene, or tetrahydrofuran and a tertiary compound such as vilison. 3 by converting it into an intramolecular term using a class amine.
Limuscon can be prepared by obtaining -methyl-2-one and pentadecen-1-one and hydrogenating it (see % 85536/1983).

As mentioned above, in the present invention, 2,15-hexadecanedione, which is an intermediate of muscone, can be produced in a simple manner and in high yield using easily available tetradecanedioyl chloride as a starting material. It can be said that this is largely due to the synthesis of Muscone.

The present invention f will be explained in more detail by showing examples below.

Example 1 Crystals of tetradecanedioic acid (300%) prepared by fermentation method
f,! : Chloride f, t = #600 ynl
(approximately 9805') was placed in a 2.8 volume flask and reacted for 3 to 4 hours by stirring with a magnetic cooler while slowly heating (approximately 35°C) in an oil path.
A homogeneous and transparent solution of acid chloride in thionyl chloride was obtained. The flask was brought to room temperature under reduced pressure with an aspirator to distill off the thionyl chloride in the solution in the flask, and was further degassed using a vacuum pump until a constant weight was reached to completely remove the thionyl chloride. Oil chloride 3372 was obtained.

10 f of zinc powder is immersed in an aqueous solution containing 2.51 F of copper sulfate to precipitate metallic copper on the surface, and the resulting zinc/copper powder, 50 g of dioxane, and 30 m of methyl iodide are refluxed. The mixture was placed in a flask equipped with a condenser and stirred at a temperature of 80° C. for 2 hours to produce methylzinc iodide. Then, the solution containing methylzinc iodide was collected in a flask by decantation, and the tetradecanedioyl chloride 41 prepared above was added thereto at a temperature of 0° C., and the mixture was reacted with stirring for 2 hours. 2,15-hexadecanecymene was synthesized.

After removing the solvent by washing the obtained 7 and the reaction solution with 20 ml of 3-polyhydrochloric acid and 20 ml of thorium hydroxide bath solution and 29 ml of pure water, the product was recrystallized with methanol to obtain 7. , 15-hexadecanedione was obtained.

Example 2 Alloy f made by melting 90 parts by weight of zinc and 10 parts by weight of copper
: Alloy powder crushed to 100 mesh or less 10? and 59ml of toluene. 10M ethyl acetate and 20ml of acetonitrile were placed in a flask equipped with a reflux condenser, and the mixture was stirred at reflux temperature for 2 hours to produce methylzinc cyanide. The solution containing methylzinc cyanide was then collected in a flask by decantation, and to this was added dropwise tetradecanedioylchloride F4y prepared from Example IK over about 1 hour while stirring at a temperature of 20 °C. The reaction mixture was stirred for an additional hour to synthesize 2, 5-hexadecanedione. The resulting reaction solution was thoroughly washed with water, the organic solution layer was concentrated and separated, and the product was recrystallized from methanol to obtain 2.41 g of pure 2,15-hexadecanedione.

Example 3 Muethyl ether 1 containing methylmagnesium bromide 159
30 r'l of zinc bromide was added to the 00M solution at a temperature of 0.degree. C. and reacted with stirring to produce methylzinc bromide. This ether layer was placed in a flask, and while the temperature was kept at -10°C, tetradecanedioyl chloride 62 prepared according to Example 1 was added thereto and reacted with stirring for 3 hours. Obtained reaction product liquid f: 3% hydrochloric acid 2ON, trihydroxide]
・Rium aqueous solution 20ml1. and washed with 20ml of pure water (
After removing the solvent at step 2, the product was recrystallized from methanol and pure 2,15-hexadecanedione was obtained at 38
2 was obtained.

Agent Yoshio Kawame

Claims (1)

[Claims] fil A method for producing 2,15-hexadecanedione, which comprises reacting tetradecanedioic acid with a chlorinating agent, and then reacting the obtained tetradecanedioyl chloride with leaded methyl halide or pseudomethyl lead halide. .