JPS6111210B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention efficiently converts hexadecane-2,15-dione into 3-methyl-2-cyclopentadecene-1.
For more information on the method of manufacturing −on,
The present invention relates to a method for producing 3-methyl-2-cyclopentadecen-1-one by intramolecularly cyclizing hexadecane-2,15-dione using an organoaluminum compound and a tertiary amine. 3-Methyl-2-cyclopentadecen-1-one (hereinafter abbreviated as MCPO) is noteworthy as a raw material for muscone because muscone, a natural musk-based fragrance, can be obtained by hydrogenating it. It is a compound. However, there are still few reports on methods for synthesizing MCPO, and the known methods have extremely low yields. For example, Helvetica Chimica Acta
Acta) Vol. 30, p. 2019 (1947) describes the reaction formula shown below in which hexadecane-2,15-dione (hereinafter abbreviated as HDO) is reacted with magnesium bromide-N-methylanilide in the presence of magnesium bromide-N-methylanilide. A method for synthesizing MCPO by intramolecular cyclization according to the method has been reported, but the yield is only 17% at most. 〓〓〓〓
Therefore, the present inventors conducted intensive studies on a method for improving the drawbacks of the conventional technology and synthesizing MCPO from HDO in good yield. As a result, the present inventors discovered a new condensing agent with high activity and high selectivity. He has completed his invention. In other words, the purpose of the present invention is to obtain high yield from HDO.
It is an object of the present invention to provide a method for producing MCPO, and an object of the present invention is to convert HDO into a compound of the general formula

[Formula] (In the formula, R ₁ and R ₂ represent an alkyl group, and R ₃ represents an aryl group, an acyl group, or an alkanesulfonyl group.)
This is achieved by intramolecular cyclization using an organoaluminum compound represented by the formula and a tertiary amine. In the present invention, it is necessary to use the organoaluminum compound described above and a tertiary amine in combination. In the organoaluminum compound used, R ₁ and R ₂ in the general formula are alkyl groups such as methyl, ethyl, propyl, butyl, hexyl, octyl, etc., and R ₃ is phenyl, tolyl,
Aryl groups such as xylyl, chlorophenyl, aminophenyl, nitrophenyl etc.; acyl groups such as formyl, acetyl, propionyl, butyryl, valeryl, octanoyl, naphthoyl, benzoyl etc.; or acyl groups such as methanesulfonyl, trichloromethanesulfonyl, trifluoromethanesulfonyl, ethanesulfonyl etc. It is represented by an alkanesulfonyl group such as diethylaluminum phenoxide, diethylaluminum chlorophenooxide, diethylaluminum octanoate,
Examples include diethylaluminium trifluoromethanesulfonate, diisobutyl phenoxide, diisobutyl aluminum benzoate, diisobutyl aluminum trifluoromethane sulfonate, dihexyl aluminum phenoxide, dioctyl aluminum phenoxide, and the like. Among these, good results are obtained when R ₃ is an aryl group. On the other hand, specific examples of tertiary amines include pyridine, picoline, lutidine, quinoline,
Examples include trimethylamine, triethylamine, tributylamine, trihexylamine, tricyclohexylamine, dimethylaniline, etc.
Any type of cyclic amine, aliphatic amine, or aromatic amine may be used. However, compounds with nucleophilic properties such as primary or secondary amines are unsuitable. The ratio of organoaluminum compound and tertiary amine used is usually 1 part organoaluminum compound to tertiary amine.
The amount of tertiary amine per mole is 0.1 to 5 mol, preferably 0.5 to 4 mol, and if the tertiary amine is outside this range, the yield tends to decrease. In the present invention, the intramolecular cyclization reaction of HDO is carried out using these two components in the presence of an inert solvent. The solvent used in this case may be any solvent as long as it is inert to the reaction, and specific examples include aliphatic solvents such as pentane, hexane, heptane, octane, and cyclohexane, benzene, toluene, and xylene. Examples include aromatic solvents and polar solvents such as tetrahydrofuran, dioxane, and diethyl ether, which are appropriately selected and used depending on the reaction temperature. In addition, it is appropriate to perform the intramolecular cyclization reaction of HDO using a large excess of an inert solvent, and usually HDO is gradually supplied to a dilute solution of the condensing agent, preferably a dilute solution of 5% by weight or less. It is carried out according to the method. At this time, as the HDO concentration in the system increases, polymers are more likely to be formed due to intermolecular aldol condensation, so the HDO concentration in the system is 1 wt.
% or less. In the present invention, the reaction is carried out in the presence of the above-mentioned condensing agent and inert solvent, but the reaction temperature and reaction time may be appropriately selected depending on the type of condensing agent used, and usually is -78~
It is carried out in the range of 150°C for 1 to 30 hours.
However, when using an organoaluminum compound in which R ₃ in the above general formula is represented by an aryl group or an acyl group, it is appropriate to set the reaction temperature to 30 to 100°C. The amount of the condensing agent to be used may be selected appropriately, but it is usually 1 to 10 mol, preferably 3 to 10 mol, of the organoaluminum compound per mol of HDO charged.
5 mol, and as the amount used exceeds the above range, the reactivity decreases. Furthermore, among the condensing agents used in the present invention, the organoaluminum compound can be prepared in advance and added, but it can also be prepared in-system using two types of compounds, such as dialkyl aluminum hydride and phenols. It can be easily synthesized by a method of introducing a dialkyl aluminum halide and a phenolate, or the like. After the reaction is completed, MCPO is separated according to a conventional method, but according to the present invention, the desired MCPO can be obtained in a much higher yield and higher selectivity than in conventional methods. The present invention will be explained in more detail with reference to Examples below. Example 1 After purging the flask with nitrogen, 20 ml of tetrahydrofuran (THF) and 0.414 g of phenol (4.4 m
After cooling to 0℃, diisobutyl aluminum hydride (DIBAL) is added.
0.568g (4.0mmole, 0.91 per mole of phenol
2 ml of n-heptane solution (equivalent to molar amount) was slowly added dropwise to synthesize diisobutylaluminum phenoxide in the reaction system. It was confirmed that this reaction proceeded very quantitatively by measuring the amount of hydrogen generated. Next, 3.8 ml (4.8 mmole) of pyridine and 80 ml of n-hexane were added, the temperature was raised to 70°C, and HDO
0.254 g (1.0 mmole) in 40 ml of THF solution (0.25 g/mol diisobutylaluminum phenoxide)
molar equivalent) was added dropwise over 11 hours under reflux,
After the dropwise addition was completed, the mixture was further stirred for 1 hour. After the reaction was completed, dilute hydrochloric acid was added to separate the organic layer and the aqueous layer, and then ether was added to the aqueous layer to extract the organic matter. The resulting organic material was then washed with a 5% aqueous sodium hydroxide solution to remove residual phenol, further washed with brine, and dried over magnesium sulfate to obtain a yellow oil. When this oil was purified by silica gel column chromatography, 0.148 g of a colorless and transparent oil was obtained. Analysis of this product by NMR and IR confirmed that it was MCPO. Further, when this product was hydrogenated using a palladium/carbon rack catalyst, d.l-muscone was obtained.
The yield in this reaction was 62%. Examples 2 to 8 Reactions were carried out in the same manner as in Example 1, except that predetermined amounts of various tertiary amines shown in Table 1 were used in place of the pyridine used in Example 1. The results are shown in Table 1.

[Table] From this result, even if the amount of pyridine used is changed,
Also, even if the type of tertiary amine is changed, the yield is high.
It can be seen that MCPO is obtained. Example 9 Phenol was used in place of the phenol and diisobutylaluminum hydride used in Example 1.
When the reaction was carried out in the same manner as in Example 1 except that diethylaluminum phenoxide was synthesized in the system using 4.4 mmole of sodium salt and 4.0 mmole of diethylaluminium chloride, MCPO was obtained in a yield of 58%. Ta. Example 10 Example 1 except that 4.4 mmole of p-cresol was used instead of the phenol used in Example 1.
When the reaction was carried out in the same manner as above, the yield was 47%.
MCPO was obtained. Example 11 Benzoic acid was used in place of the phenol used in Example 1.
The reaction was carried out in the same manner as in Example 1 except that 4.4 mmole was used, and MCPO was obtained in a yield of 44%. Example 12 Diisobutylaluminum trifluoromethanesulfonate was synthesized in the same manner as in Example 1, except that 4.4 mmole of aluminum trifluoromethanesulfonate was used in place of the phenol used in Example 1, and the reaction was performed with DIBAL at -70°C. did. Next, the reaction temperature was set to 0° C. and the reaction was carried out according to the example, and MCPO was obtained in a yield of 44%. Example 13 The reaction was carried out in exactly the same manner as in Example 1 except that the reaction temperature was changed to 50°C or 90°C, and MCPO was obtained in yields of 46% and 42%, respectively. Comparative Example 1 The reaction was carried out in the same manner as in Example 1 except that pyridine was not used, and the yield of d·l-muscone was 10% or less. Comparative Example 2 The reaction was carried out in the same manner as in Example 1 except that diisobutylaluminum phenoxide was not used, and the yield of d·l-muscone was 10% or less. 〓〓〓〓

Claims (1)

[Claims] 1 Hexadecane-2,15-dione is prepared by the general formula (In the formula, R ₁ and R ₂ represent an alkyl group, and R ₃ represents an aryl group, an acyl group, or an alkanesulfonyl group.) Intramolecular cyclization is performed using an organoaluminum compound represented by 3-methyl-2-cyclopentadecene-1-, which is characterized by
On manufacturing method. 2. The method according to claim 1, wherein R ₃ in the general formula is an aryl group. 3. The method according to claim 1, wherein the ratio of the organoaluminum compound and the tertiary amine used is in the range of 0.1 to 5 moles of the latter per 1 mole of the former. 4. Intramolecular cyclization reaction of hexadecane-2,15-dione is carried out by gradually feeding hexadecane-2,15-dione into a dilute solution of an organoaluminum compound and a tertiary amine. A method according to claim 1.