JPS5831330B2 - 1-hexadecin-6-one - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a novel compound l-hexadecyn-6-one.

The compounds of the present invention can be applied to Orgia pseudotsugata (Orgia pseudotsugata).
This compound is useful as an intermediate for the synthesis of the sex hormone cis-6-henairasen-11-one produced by A.ta (McDunnough).

Conventional synthesis of cis-6-henairasen-11-one was performed by Smith et al.

Daves Jr.) (J, O
rg.

Chem, 40, 1593 (1975)).

This method is a method for deriving cis-6-henairasen-11-one from C1oH21CHO, but this method has two drawbacks: (a) the starting material compound is not easily available, and (b) trimethylene, which has a strong odor, is used as a reagent. There is a risk of environmental pollution due to the use of thioglycol and toxic heavy metals such as chromium oxide, copper oxide, and nickel.
c) There are drawbacks such as the need to completely recover the reagent, which inevitably increases production costs, and this poses difficulties in industrialization.

However, when the compound of the present invention is used as a starting material, the above-mentioned trimethylenethioglycol and toxic heavy metals are not used, and therefore the above-mentioned (a), (b), and (e) can be obtained.
) by eliminating all the drawbacks of cis-6-heneicosene 11
- can be produced.

The compound 1-hexadecyn-6-one of the present invention is a novel compound discovered for the first time by the present inventor, and can be produced, for example, by the following formula using easily available known dihydroresorcinol as a starting material.

Compounds of formula (II) can be prepared by known methods COrg, Syn.

Co110.5.539], for example, by reacting dihydroresorcinol [■] with ethanol in the presence of p-4 luenesulfonic acid.

Then, the compound of the formula [river] and the general formula n -C1o
A halide represented by H21X (in the formula, A novel compound of formula (IV) can be obtained by hydrolyzing the compound of formula [■] with a common acid such as hydrochloric acid or sulfuric acid without isolating the compound of formula [■].

The amount of alkali metal used in these reactions is expressed by formula (II)
The amount of the halide used is usually an equimole to an excess amount, preferably 3 to 5 times the mole of the compound, and the amount of the halide used is usually an equimole to an excess amount per mole of the compound of the formula [river]. , preferably equimolar to 1 to 2 times the molar amount.

These reactions can be carried out at room temperature, cooling or heating, and are usually carried out at -78°C to 40°C, preferably at room temperature, and the reaction time is about 1 to 5 hours.

A novel compound of formula (V) can be obtained by subjecting the compound of formula (IV) to an epoxidation reaction in a solvent such as water, methanol, ethanol, methylene chloride, or carbon tetrachloride.

As the filter acid used in this epoxidation reaction, a wide variety of known filter acids can be used, such as methachloroperbenzoic acid, peracetic acid, hydrogen peroxide, and the like.

For certain L., sodium hydroxide or potassium hydroxide may be used together with the above peracid.

When using these alkalis, it is recommended to prepare them in advance as sodium salt of hydrogen peroxide, potassium salt of hydrogen peroxide, sodium salt of t-butyl hydroperoxide, potassium salt of t-butyl hydroperoxide, etc. desirable.

In the present invention, among these, hydrogen peroxide is used) IJ
Particularly preferred is the sodium or potassium salt of tert-butyl hydroperoxide.

The amounts of filtered acid and alkali used in the reaction are determined by the formula (I
The amount of I7 per mole of compound V) is equimolar excess (preferably 3 to 5 times the mole) and 03 to 2 times the mole (preferably 0.5 times the mole).

The reaction is carried out at room temperature or under cooling, and is usually 20 to 3
The temperature is 0°C, preferably 20-25°C, and the reaction time is usually 1
~6 hours.

The compound of the present invention (compound of formula (Vl)) is obtained by subjecting the compound of formula [■] obtained above to Eschenmoser cleavage reaction.

The Etsien-Mosel cleavage reaction is a reaction in which a carbonyl group and a triple bond are introduced into the molecule by cleavage of α/β-epoxyketone (J.

Ory, Chem, 40 (5), 57.9 (19
75)].

According to this reaction, as explained in detail below, the compound of the present invention is produced by treating the compound of formula (V) in a solvent in the presence of an appropriate catalyst.

Examples of catalysts used in this reaction include arylsulfonyl hydrazides such as p-toluenesulfonyl hydrazide, p-nitrophenylsulfonyl hydrazide, and phenylsulfonyl hydrazide, and lower alkylsulfonyl hydrazides such as ethylsulfonyl hydrazide. It is preferable to use

Examples of the solvent used in the reaction include methylene chloride, chloroform, 1,2-dichloroethane, acetic acid, formic acid, ether, dioxane, dimethylformamide, and dimethylsulfoxide.

In the present invention, methylene chloride-acetic acid or chloroform-
Preferably, a mixed solvent of acetic acid is used.

The amount of the catalyst used in the reaction is not particularly limited, but is usually 05 to ※※1.5 per mol of the compound of formula [■].
The amount is twice the molar amount, preferably about the same molar amount.

The reaction can be carried out at room temperature, cooling or heating, but is generally carried out at 0 to 50°C, preferably at 0°C.
to room temperature, and the reaction time is usually 3 to 10 hours.

In each of the above reactions, the desired compound can be obtained in good yield.

Using the compound of the present invention thus obtained as a starting material, L.
For example, by performing the reaction shown in the following formula, cis-
6-heneicosen-11-one can be produced.

In the above formula, n represents 2 or 3, and X represents a halogen atom.

Examples and application examples are listed below to further clarify the present invention, but the present invention is not limited thereto.

Example 3 - Preparation of decyl-2-cyclohexenone (compound of formula (IV)) A small piece of lithium 8707Q was added to dry tetrahydrofuran, and the mixture was stirred at 20-30°C under a stream of nitrogen.
A mixture of 7fI of -ethoxy-2-cyclohexenone and 13.3P of n-decyl bromide is added dropwise.

After the dropwise addition, the mixture was stirred at room temperature for 1 hour, and then excess lithium was removed by P, and the mother liquor was poured into cold dilute sulfuric acid for ether extraction.

The ether solution is washed with saturated aqueous sodium bicarbonate solution, then saturated brine, and dried over magnesium sulfate.

The solvent was distilled off and the residue was distilled under reduced pressure to obtain 3decyl-2-cyclohexenone.

Yield 9.9? ; Yield 846%; Boiling point 130-132℃1
0.3 mHg 3-decyl-2,3-epoxycyclohexanone (formula (
Preparation of compound V) 3-decyl-2-cyclohexenone was dissolved in 9.61 ml of methanol (H) and cooled to 10°C.

16 rules of 30% hydrogen peroxide solution was added dropwise to this while stirring, and then 3.5 ml of 6N sodium hydroxide was added over 5 minutes while maintaining the temperature at 15-20°C.
Stir for 3 hours.

The reaction solution was poured into water and extracted with ether.

The ether solution is washed with water, then with saturated saline, and then dried over magnesium sulfate.

The solvent was distilled off and the residue was distilled under reduced pressure to obtain 3-decyl 2,3-epoxycyclohexanone.

Yield: 9.1 g; Yield: 90.4%; Boiling point: 125-126°C
10.2 mmHg Production of l-hexadecyn-6-one (compound of formula (M)) Dissolve 5 g of 3-decyl-2,3-epoxycyclohexanone in 20 ml of methylene chloride and 10 TIL of acetic acid,
To this, 3.7 g of p-toluenesulfonyl hydrazide is added at once while stirring at 0 to 2°C, followed by stirring at 0 to 2°C for 3 hours, and further stirring at room temperature for 3 hours.

The reaction solution was poured into water and extracted with n-hexane.

The n-hexane solution is washed with water, saturated aqueous sodium bicarbonate, and saturated brine in this order, and dried over magnesium sulfate.

Concentrate under reduced pressure and distill the residue under reduced pressure to obtain 1-hexadecine-6
- Get on.

Yield 411; Yield 87.2%; Boiling point 122-123°C/
0.8 mmHg.

It solidifies and is recrystallized from petroleum ether to give colorless prismatic crystals.

(Melting point 27-28°C). 2.51 of l-hexadecine-6one is obtained in the same manner as above except that 2.22 of O ethylsulfonyl hydrazide is used.

Application example 1-Hexadecin-6-one-ethylene ketal (formula [
■Production of compound) 1-hexadecin-6one 3t1 ethylene glycol 0.9? Then, 5 m9 of hypotonic sulfonic acid was dissolved, and a water separator was attached to the solution to reflux for 6 hours.

After cooling, it is washed with saturated sodium bicarbonate solution, then saturated brine, and dried over magnesium sulfate.

Benzene is distilled off and the residue is distilled under reduced pressure to obtain 1-hexadecyn-6-one-ethylene ketal.

Yield: 3.2 g; Yield: 88.9%; Boiling point: 120-125°C
10.3 Hg 6-heneicodin-11-one-ethylene ketal (
Preparation of compound of formula [■]) Add 1-hexadecine to 15 ml of dry tetrahydrofuran.
2.8 liters of 6-one-ethylene ketal is dissolved, and 6.6 liters of a solution of n-butyllithium (1.7 mol) in n-hexane is added dropwise to this solution while stirring under ice cooling.

Stir for 15 minutes at room temperature, then add 25 TL of a solution of 3 g of amyl bromide in dry phosphoric acid hexamethyltriamide.
1 was added dropwise while stirring under ice-cooling, and the mixture was stirred for 1 hour under water-cooling.

The reaction solution was poured into ice water and extracted with n-hexane.

The n-hexane solution is washed with water and saturated brine, and dried over magnesium sulfate.

The solvent was distilled off and the residue was distilled under reduced pressure to obtain 6-heneicosine.
11-one-ethylene ketal is obtained.

Yield 3.11 Yield 88.6%; Boiling point 165-168℃1
0.3mmHg 6-heneicosin-11-one (compound of formula [■])
Production of 6-heneicodin-11-one-ethylene ketal 1
5 g was dissolved in 15 ml of tetrahydrofuran, then 5 ml of 3N perchloric acid was added thereto, and the mixture was left overnight in the refrigerator.

Tetrahydrofuran is distilled off, the residue is diluted with water, and extracted with ether.

The ether solution is washed with saturated aqueous sodium bicarbonate solution, then saturated brine, and dried over magnesium sulfate.

The ether is distilled off and the residue is distilled under reduced pressure to obtain 6-heneicosine 11-one.

Yield 1.2 g; Yield 91.6%; Boiling point 145-150°C
/ 0.2 mm Hgcis-6-henaocosene-1
Preparation of 1-one (compound of formula [X]) Dissolve 0.9r of 6-heneicosin-11-one in 15ml of methanol, then add 150ml of 5% palladium-barium sulfate and 2 drops of quinoline and shake. Absorb hydrogen at room temperature and normal pressure.

The catalyst was removed and the mother liquor was concentrated under reduced pressure.

The residue is dissolved in ether, washed successively with dilute hydrochloric acid, saturated aqueous sodium bicarbonate, and saturated brine, and dried over magnesium sulfate.

The ether was distilled off and the residue was distilled under reduced pressure to obtain cis-6-henaocosen-11-one.

Claims (1)

[Claims] 1 set 1-Hexadecin-6-one represented by: