JPS6048494B2 - Method for producing δ, ε-unsaturated ketones - Google Patents

Description

[Detailed description of the invention] The present invention is based on the general formula [I] (X,,X in the formula.

,X. ,X. ,R,,R. , l, 4 and n have the same meanings as in formula ■), δ, E−
Method for producing unsaturated ketones. 2 General formula [■] (In the formula, X and X2 are both hydrogen atoms, or one is a hydrogen atom and the other together with A represents a single bond, Z, is X, or X.

together represent a single bond or a hydrogen atom, a hydroxyl group or a lower alkoxy group, R, is a hydrogen atom or a lower alkyl group, and X3 and X. are both hydrogen atoms, or one is a hydrogen atom and the other together with 4 represents a single bond, and Z2 is X3 or X. together with R represents a single bond, or represents a hydrogen atom, a hydroxyl group or a lower alkoxy group, and R. is a hydrogen atom or a lower alkyl group, n is 0 or 1, and Ha
A halogen compound represented by the general formula [■] (wherein Xl, X2, X3, X4,
R1, R2, Z-1, Z2 and n have the same meanings as in formula [■]), and the β,γ monounsaturated ketone was treated with a vinyl Grignard reagent. By reacting or by partial hydrogenation after ethynylation reaction, the general formula [■] (in the formula, X,,X.

,X. ,X. , R,, R2, Zl, 4 and n are the formula [■
The general formula [I] (in the formula, X, , X) is an allylic alcohol represented by

,X3,X. ,R,,R2,A,4 and 冫n are the formulas [
■Production method of monounsaturated ketones represented by δ and ε, which have the same meaning as those in [].

Detailed Description of the Invention The present invention is based on the general formula [I] (wherein X and X2 are both hydrogen atoms or one is a hydrogen atom, the other together with B represents a single bond, and B is X, or together with X2 represents a single bond or is a hydrogen atom, a hydroxyl group or a lower alkoxy group, R is a hydrogen atom or a lower alkyl group, and X3 and X are both hydrogen atoms; , or one is a hydrogen atom and the other together with Z represents a single bond, and Z, together with X3 or X4 represents a single bond, or is a hydrogen atom, a hydroxyl group or a lower alkoxy group; , R2 is a hydrogen atom or a lower alkyl group, and n is 0 or 1).

The 6,E-unsaturated ketone represented by the general formula [1] (hereinafter referred to as 8,E-unsaturated ketone [1]) can not only be used as a fragrance itself, but also as a fragrance, cosmetic base, It is also an effective substance as an intermediate in the production of medicines, agricultural chemicals, etc.

According to the present invention, the general formula [H] (wherein X,, X2, X3, X4, R,, R2, O, Z2
and n have the same meanings as in general formula [1]) (hereinafter, this 1
8,E-unsaturated ketone [1] can be produced by heating and isomerizing allylic alcohol [n].

Allyl alcohol [n] has the general formula [W] (formula X, ,
2, X,, , which is expressed as a halogen compound [w]) with mesityl oxide in the presence of an alkal condensing agent, the compound of the general formula ID (wherein Xl9X29X39X49Rl! It can be easily produced by reacting a P,Y monounsaturated ketone represented by (having the same meaning as those) with a vinyl Grignard reagent or by partially hydrogenating it after an ethynylation reaction.

1 In the condensation reaction between the halogen compound [■] and mesityl oxide, the general formula [v] (wherein Xl, X2
, X3, X4, Rl, R2, Zl, ro and n have the same meanings as in general formula [I]) It was found that α,β-monounsaturated ketone [V] is easily isomerized to β,γ-unsaturated ketone [■].

Therefore, at least a portion of the α,β-monounsaturated ketone [V] obtained as a co-product by the condensation reaction of the halogen compound [■] and mesityl oxide can be converted into β,γ-monounsaturated ketone [V].
An additional amount of allylic alcohol [■] can be obtained by isomerizing it to [2] and reacting it with a vinyl Grignard reagent, followed by partial hydrogenation after the ethynylation reaction. Also, in the reaction of β,γ monounsaturated ketone [■] with vinyl Grignard reagent or ethynylation reaction,
Depending on the reaction conditions, α,β2-unsaturated ketone [V]
may be produced as a by-product, but this by-product α, β monounsaturated ketone [V] is also isomerized to β, γ monounsaturated ketone [■] if desired, and then reacted with a vinyl Grignard reagent or ethynylation reaction. Allyl-type alcohol [■] can be obtained by subsequent partial hydrogenation. Preferred examples of the new allylic alcohol [■] used in the method of the present invention include the following compounds.

However, the following structural formula is not intended to specify the three-dimensional structure of the compound. Dodecar 1,6,10-trien-3-ol 4-isopropenyl-3,7,11
-trimethyldodecar 1,10-dien-3-ol 4
-isopropenyl-3,7,11-trimethyldodecar 1,6-dien-3-ol 4-isopropenyl-3,
11-dimethyl-7-ethyltridecar 1,6,10-
triene-3-ohnore-4-isoph-benyl-3,7,
11-trimethyldodecar-1-ene-3,11-diol 4-isopropenyl-3,7,11-trimethyl-1
1-Methoxidedodecar-1-en-3-ol Among these allyl alcohols, those with the following general formula [Ha] (
In the formula, the dotted line indicates 2 points at any of the positions indicated by this.
Indicates that a species bond may be present, and n is 0 or 1).
By heating and isomerizing in a temperature range of 200°C, 8, which is useful as a raw material for the synthesis of isophytol, an intermediate in the production of vitamin E, or squalane, a cosmetic base.
E is particularly important because it is easily exchanged to monounsaturated ketone [1a].

Of the allylic alcohols [n], the general formula [Na
] Of course, compounds not included in the above are also treated in the same manner as above to produce the corresponding linear 8,E-unsaturated ketones.

As shown in the example below, the typical manufacturing method for terpenoid compounds that has been used conventionally requires long reaction steps and
C. Since expensive diketene or isopropenyl ether is used as an extender, there is a problem in that the extender accounts for a large proportion of the manufacturing cost.

According to the method of the present invention, a novel allylic alcohol [Π]
As can be understood from what has already been explained, by using the method, it is possible to produce compounds that are the same or similar to compounds produced by conventional methods, with shortened reaction steps and at low production costs.

Next, the method of the present invention will be explained in more detail.

β,γ-monounsaturated ketone [
[2] In producing [2], a method known as a method for producing substituted ketones by a condensation reaction between an organic halogen compound and a ketone, such as the method 8. (B) and (C) below, is used. Something will happen.

^: A method of condensing a halogen compound with a ketone in the presence of an alkali amide in liquid ammonia (Special Publication No. 4)
0-19091 and 40-22173).

(B): A method in which an organic halogen compound and a ketone are reacted in a non-aqueous system in the presence of an alkaline condensing agent and an amine catalyst or a phosphonium catalyst (see Japanese Patent Publication No. 40-22251 and Japanese Patent Application Laid-open No. 50-96514).

In addition, in the specification of Japanese Patent Publication No. 40-22251, Example 67, which shows an example of the reaction between pre-renyl chloride and mesityl oxide, shows that condensation occurred on the methyl group side of the ketone.
8-dimethyl-2,7-nonadien-4-one with a yield of 7
However, as a result of detailed reexamination of Example 67 by the present inventors, the yield of 2,8-dimethyl-2,7-nonadien-4-one was about 5% at most, and 3 −
The total yield of isopropylidene-6-methyl-5-hepten-2-one and 3-isopropenyl-6-methyl-5-hepten-2-one was 70% or more). One (C
): Alkaline condensing agent and catalyst (amine catalyst,
A method of reacting an organic halogen compound with a ketone in the presence of a quaternary ammonium salt catalyst or a phosphonium salt catalyst (Japanese Unexamined Patent Publication Nos. 50-37713 and 50-96)
(See Publication No. 514).

Among these methods, the one that is used industrially is (
Methods B) and (C) are preferred, and method (C) is particularly preferred. Comparing method (B) and method (C), method (C) generally has a faster reaction rate and does not require the use of an alkaline condensing agent in a solid state, which reduces the reproducibility of the reaction and the work environment. It has advantages such as excellent In carrying out the condensation reaction between the halogen compound [■] and mesityl oxide, the same reaction conditions as in the above-mentioned known methods can be employed, but preferred methods (B) and (C ), it is preferable to use sodium hydroxide or potassium hydroxide as the alkali condensing agent, and the amount used ranges from 10 molar equivalents to the charge of the halogen compound [■].
A range of up to twice the mole is preferred, and a range of about 1.5 to 4 times the mole is particularly preferred.

As the catalyst, primary amines, secondary amines, tertiary amines, salts of these amines, quaternary ammonium salts and phosphonium salts can be used, and among them, quaternary ammonium salts and bos. Honium salts are particularly preferred. Specific examples of recommended catalysts include tetrabutylammonium chloride, trimethylbenzylammonium chloride, trimethyllauryl ammonium chloride, trimethylcetylammonium chloride, trimethylstearylammonium chloride, trimethylstearylammonium chloride, trimethylstearylammonium bumide, and dimethyldicyclohexylphosphonium chloride. , methyltricyclohexylphosphonium chloride, ethyltricyclohexylphosphonium chloride, ethyltricyclohexylphosphonium bromide, and the like.

The amount of catalyst depends on the type of catalyst used, but generally ranges from about 0.001 mol% to about 20 mol%, preferably from about 0.005 mol% to about 2 mol%, based on the amount of halogen compound [■] charged. The range is preferably up to .0 mol%.

When employing the above method (C), it is preferable to supply the alkali condensing agent to the reaction system in the form of an aqueous solution, and the alkali condensing agent concentration in the aqueous alkali condensing agent solution is from about 40% by weight to about 65% by weight. A range of is suitable. Method(
In B) and (C), the reaction temperature is 0°C to 100'
The temperature can be arbitrarily selected within the range of C, but from the viewpoint of reaction rate and selectivity, a temperature of about 20°C to about 70°C is particularly preferred. The time required for the reaction varies depending on the type of catalyst, catalyst concentration, amount of alkali condensing agent, etc., but for example, when the amount of alkali condensing agent is about equimolar to the halogen compound [■], it will take about 10 to 3011 Terama, When the amount of the alkali condensing agent is about 1.5 to 4 times the mole of the halogen compound '[■], the reaction is completed in about 1 to m hours. In the condensation reaction between a halogen compound [■] and mesityl oxide, α and β are generally used together with β and γ monounsaturated ketones [■].
A monounsaturated ketone [V] ι is produced, but the two can be easily separated by precision distillation if desired.

Then, this α, β monounsaturated ketone [V] is converted into an isomerization catalyst,
For example, when heated in the presence of an acidic catalyst, α,β-unsaturated ketone [V] is isomerized to β,γ-unsaturated ketone [■]. Since β, γ-unsaturated ketone [■] has a lower boiling point than α, β-monounsaturated ketone [■], a mixture of the two is
It is also possible to continuously extract only the β, γ-unsaturated ketones [■] by heating and distilling the β-, β-unsaturated ketones under isomerization reaction conditions. However, from the viewpoint of reaction efficiency, it is preferable to increase the production ratio of β, γ monounsaturated ketone [■]/α, β monounsaturated ketone [V] in the condensation reaction between the halogen compound [■] and mesityl oxide. According to the research of the present inventors, when the reaction temperature is high in the condensation reaction between a halogen compound [■] and mesityl oxide, or when the reaction is continued for a long time in the presence of an excess of an alkali condensing agent, The generated β,γ monounsaturated ketones [
(2)] is reverse isomerized to α,β monounsaturated ketone [V] in the system. For example, 5.0 moles of prenyl chloride and 10 moles of mesityl oxide are combined with 7.5 moles of sodium hydroxide in 5 moles of sodium hydroxide.
When the reaction was carried out at 32 to 35°C in the presence of 24.2y of trimethylstearylammonium chloride in a 5% by weight aqueous solution, the conversion of prenyl chloride was 55% in a reaction time of 1.5 hours, and 3-isopropenyl-6-methyl-5-
The production ratio of hepten-2-one to 3-isopropylidene-6-methyl-5-hepten-2-one is 90:10, but the conversion rate of prenyl chloride is 8 in 3.5 hours.
At 4%, the production ratio was 78:22, and after a further 5 hours, the conversion rate of prenyl chloride was 93%, but the production ratio was n:23. Therefore, stopping the condensation reaction when the conversion rate of the halonogen compound (N) reaches about 70 to 80% is effective in increasing the reaction efficiency of the condensation reaction. In addition, what is the acidic catalyst when isomerizing α, β-unsaturated ketone [V] to β, γ-unsaturated ketone [■]? When considering distillation separation after isomerization or distillation separation simultaneously with isomerization, it is preferable to use an acid with a boiling point higher than that of β, γ monounsaturated ketone [■]. are, for example, aliphatic or aromatic sulfonic acids such as benzenesulfonic acid, P-toluenesulfonic acid, laurifursulfonic acid, P-toluic acid, 4-nitro-m-toluic acid, 4-hydroxybenzoic acid, vanillic acid, 4- Monocyclic, aromatic or alicyclic monocarboxylic, dicarboxylic or polycarboxylic acids which may contain foreign atoms such as nitroisophthalic acid, cyclohexanecarboxylic acid, or adipic acid, 1,2-hydroxystearic acid, benzyl saturated or unsaturated aliphatic or heteroaliphatic monocarboxylic acids, dicarboxylic acids or polycarboxylic acids, which may be hydroxylated and/or phenyl-substituted, such as p-nitrocinnamic acid, diglycolic acid, or indole acid, Examples include aliphatic or aromatic amino acids such as 1,2-diaminocyclohexanetetraacetic acid, and inorganic acids such as metaphosphoric acid and phenylphonosphinic acid.

The amount of acidic catalyst varies depending on the type, but for example, when using sulfonic acids, α,β monounsaturated ketone [V]
0. ~0.1 mol% When other acids are used, they are used at a concentration of 0.1 to 20 mol%, particularly preferably about 4 to 8 mol%, based on α,β monounsaturated ketone [V]. be done. The reaction temperature for isomerization is preferably from about 80°C to about 200°C. The β,γ monounsaturated ketone [■] thus obtained can be reacted with a vinyl Grignard reagent using a known method. Allyl type alcohol [■] can be derived by partial hydrogenation after the ethynylation reaction.

In the reaction using a vinyl Grignard reagent, for example, vinyl magnesium halide obtained by reacting vinyl chloride or vinyl bromide with metallic magnesium in tetrahydrofuran (hereinafter referred to as THF) or diethyl ether and a β,γ monounsaturated ketone [ (2)] may be reacted at a temperature range of -10 to 50°C. The following ethynylation methods have been conventionally used. Ru. (a):
Ethynylation method using Grignard reagent.

(THF) in another suitable solvent, the ketone is treated with ethynylmagnesium halide Z which may be generated in situ).

(b): Sodium, potassium, I in liquid ammonia
A method in which acetylene acts on an alkali metal or alkaline earth metal such as calcium to form acetylide, which is then reacted with a ketone.

i(c): Acetylene and How to react with ketones. (d)
: A method in which acetylene and ketone are reacted in the presence of a catalytic amount of sodium hydroxide, potassium hydroxide, sodium alkoxide, potassium alkoxide, etc. in liquid ammonia.

Method (a) can be used for small-scale synthesis, but is not suitable for large-scale operation.

Since method (b) uses a large amount of alkali, the ethynylation reaction involves reverse isomerization from β, γ monounsaturated ketone [■] to α, β monounsaturated ketone [V]. For example, metallic sodium 69 da is present in liquid ammonia 31, acetylene gas is sucked into it to form acetylide, and then 3-isopropenyl-6-methyl-heptene-2
-one (purity 99%) 5009 was added to carry out the ethynylation reaction, the composition of the product was 5% of 3-isopropenyl-6-methyl-5-hepten-2-one, 3-isopropylidene-6-methyl-5 -Hepten-2-one 1
0%, 4-isopropenyl-3,7-dimethyl-1-octyne-6-en-3-ol 85%. Method(
When the ethynylation reaction is carried out in the presence of a catalytic amount of alkali in c) and (d), there is almost no reverse isomerization from β, γ monounsaturated ketone [■] to α, β monounsaturated ketone [V]. Therefore, as the ethynylation method used in the present invention, the above methods (c) and (d) are particularly preferred. When carrying out the ethynylation reaction using methods (c) and (d), industrially, sodium hydroxide or potassium hydroxide is
．． It is preferable to use 1 to 3% by weight of W, particularly preferably 0.5 to 3% by weight, and conduct the reaction at a temperature of -5 to 5°C. α、β
Unlike β, γ monounsaturated ketone [■], monounsaturated ketone [v] hardly undergoes ethynylation under normal ethynylation reaction conditions, and β, γ monounsaturated ketone [■] This is because α,β-unsaturated ketones [V] are produced as by-products when oxidizing, and α,β-unsaturated ketones [V] and the ethynylation reaction product can be separated by distillation. Considering that, the compounds of α, β monounsaturated ketone and β, γ monounsaturated ketone [■] obtained by condensing a halogen compound [■] and mesityl oxide were directly subjected to the ethynylation process, and then distilled. Upon separation to obtain the ethynylation product, the recovered α,β monounsaturated ketone [V] is converted into β,γ monounsaturated ketone [V] in an isomerization step.
■] can also be used.

The ethynylation product obtained in this way can be chemically partially hydrogenated using lithium aluminum hydride etc. to form the compound [■], but industrially, for example, n -hexane, n-heptane,
Catalytic reduction using an appropriate hydrogenation catalyst in a hydrocarbon solvent such as octane, an alcohol solvent such as methanol, ethanol, or propanol, or an aromatic hydrocarbon solvent such as benzene, toluene, or xylene. is preferred.

Note that the α,β-monounsaturated ketone [V] produced as a by-product in the ethynylation process is hardly hydrogenated under these hydrogenation conditions, so the ethynylation reaction solution is directly hydrogenated to form an allyl alcohol [■]. Then, the α,β monounsaturated ketone [V] may be separated. The obtained allylic alcohol [■] can be heated to undergo a rearrangement reaction and be induced into a δ,ε monounsaturated ketone [I].

This rearrangement reaction can be carried out in either a liquid phase or a gas phase, and a reaction temperature of 100°C to 400°C can be used; however, in terms of reaction rate and selectivity, the liquid phase method is The temperature is preferably 130°C to 230°C, and in the case of a gas phase method, the temperature is preferably 250°C to 400°C, although it depends on the residence time. Although the reaction can be carried out in the atmosphere, it is usually preferable to carry out the reaction under an atmosphere of an active gas such as nitrogen or helium. There is no particular limitation on the reaction pressure, and the reaction can generally be sufficiently carried out under atmospheric pressure. However, if the boiling point of the allyl alcohol [■] is lower than the reaction temperature used, or if a gas phase method is employed, it is desirable to carry out the reaction under increased or reduced pressure that meets these conditions. Although the use of a solvent is not essential, any solvent that is stable under rearrangement reaction conditions and does not participate in the reaction or that improves selectivity may be used. When this reaction is diagrammed using the above-mentioned [■a] as an allyl alcohol, it becomes as follows. In other words, when electron transfer occurs between double bonds, a rearrangement reaction occurs, and when electron transfer occurs between a double bond and a hydroxyl group, a decomposition reaction proceeds. The ratio of (rearrangement reaction product) to (decomposition product) is approximately (6
0-70) versus (40-30).

Here, 4-isopropenyl-3,7-dimethyl-'(
1,6-octadien-3-ol, 4-isopropenyl-3,7-dimethyl-1,6-nonadien-3-ol, 4-isopropenyl-3,7,11-trimethyldodecar 1,6,10-trien-53-ol, 4 -isopropenyl-3,7,11-trimethyldodecar 1,6
-When using dien-3-ol, etc., the expected rearrangement reaction between the isopropenyl group at the 4-position and the double bond at the 6-position hardly proceeded, and 0x
It was surprising that the [1,3]-didamatropy reaction and the accompanying side reactions, which are normally observed in the y-'0C0pe rearrangement reaction, did not occur at all.
When the reaction route of the present invention is diagrammed using the above-mentioned [■a], it is as follows.

6,E monounsaturated ketone [Na] thus obtained
When n=o, squalane, which is useful as a cosmetic base, can be derived by reacting with diacetylene, followed by a combination of dehydration and hydrogenation reactions (
(See the following figure) In the case of n=l, after the hydrogenation reaction, isophytol, which is an intermediate for the production of vitamin E, is produced by combining ethynylation reaction and partial hydrogenation reaction or by reacting with vinyl Grignard reagent. can be guided (see figure below).

This method can solve the production cost problems of the CarrOll rearrangement reaction using diketene or the Claisen rearrangement reaction using isopropenyl ether, which have been the mainstream C3 extender in terpeide synthesis for the past few decades. In addition, there are advantages such as shortening of the reaction process, and the above-mentioned terpenoids can be produced industrially at low cost.

This will be explained in more detail in Examples and Reference Examples below.

Example 1 In a solution of 600 y of sodium hydroxide, 490 y of water, 980 d of mesityl oxide, 52 d of prenyl chloride, 250 d of trimethylstylylammonium chloride
y was added and stirred under water dissolution (the reaction temperature rose to 70'C), and the reaction was completed after 2 hours.

Pour the reaction solution into water, extract with ether, wash with water, and dry. After the solvent was distilled off under reduced pressure, the remaining 1,250 Da was distilled to recover excess mesityl oxide, and 3-isopropenyl-6-methyl-5-hapten-2-one and 3-isopropenyl-6-methyl-5-hapten-2-one and 3
-isopropylidene-6-methyl-5-heptene-2-
Obtained 560 Da of 2.5:1 admixture of On (purity 96.4
%). The purity of the prenyl chloride used was 83.71.
%, the yield of 3-isopropenyl-6-methyl-5-hepten-2-one was 60%, and the yield of 3-isopropylidene-6-methyl-5-hepten-2-one was 2/%. When the above mixture is distilled and separated using a precision rice distillation column with 30 theoretical plates, the Bp is 32-34° ((0
．． 21T1mHg), 3-isopropenyl-6-methyl-5-hepten-2-one was
3-isopropylidene-6-methyl-5-hepten-2-one was obtained from the 8°C (0.2 rnmHg) fraction. These structures were confirmed by the following method. Infrared absorption spectrum (CrIL-1) 1714('/C
=0)1642(〉C=C.(),1445,137
8,1353,1153,900, nuclear magnetic resonance spectrum (AWp.nCCI, infrared absorption spectrum (Cm-
1) 1688 (>C=O), 1615 (>C=Cku),
1440, 1375, 1350, nuclear magnetic resonance spectrum (δWp..CCI4) The obtained 3-isopropylidene-6-methyl-5hepten-2-one 130y is 7y (
7) It was put into the bottom of a precision distillation column with 50 theoretical plates together with Trans-1,2-cyclohexanedicarphonic acid and distilled at a vacuum degree of 30 nmHg and a reflux ratio of 30/1 to obtain distillate 107.

As a result of gas chromatography analysis, this product was found to be 3-isopropenyl-6-methyl-5-hepten-2-one (
94%) and 3-isopropylidene-6-methyl-5-hepten-2-one (6%). 3 above
-Isopropenyl-6-methyl-5-hepten-2-one 410y was used to carry out the following ethynylation reaction.
Liquid ammonia 3' was placed in a 5f-3-bottle flask, 70y of metallic sodium was added thereto, and then acetylene gas was blown into the flask.

When the reaction solution turned gray, the blowing of acetylene gas was stopped, 3-isopropenyl-6-methyl-5-hepten-2-one (517) was added, and then acetylene gas was blown into the reaction mixture and the mixture was reacted for 3 hours. After removing ammonia, the mixture was neutralized with ammonium chloride, poured into water, and extracted with ether. After drying with borax, the solvent was removed under reduced pressure. The residue 524q was distilled under reduced pressure to a Bp of 5.9 to 61°C (A). 5
A fraction 519y of mmHg) was obtained. This product is 3-isopropenyl-6-methyl-5-hepten-2-one (2
%), 3-isopropylidene-6-methyl-5-hepten-2-one (8%), 4-isopropenyl-3,7-
Dimethyl. -6-octene-1-yn-3-ol (9
0%) mixture. The structure of the main component was confirmed by the following method. Yi magnetic resonance spectrum (δW,n, CCI
4) Next, 500 y of 4-isopropenyl 3,7-dimethyl-6octen-1-yn-3-ol was dissolved in 1.5 ml of n-hexane, and the mixture was heated to room temperature and pressure using 0.25% palladium-Lindlar catalyst 25 d. The hydrogenation reaction was carried out in a streamer system.

Gas chromatography (PEG2O
The reaction is terminated after confirming the disappearance of the raw material propargyl type alcohol. The catalyst was separated, the solvent was distilled off under reduced pressure, and the residue was distilled under vacuum to obtain B.
At P55-59°C (a). 4 mmHg) as a fraction of
482y of -isopropenyl-3,7-dimethyl-1,6-octadien-3-ol was obtained. The residue was again subjected to high vacuum distillation to obtain a fraction 12y with a Bp of 77-87C (0.15 mmHg). This one is 6,10 according to the following analysis.
-dimethyl-6,9-undecadien-2-one. Infrared absorption spectrum (Clrl-1) 3480 (
-0H), 163○℃=C(), 1450, 1376,
998,922,895 nuclear magnetic resonance spectrum δWP
mCCI4 infrared absorption spectrum (Cm-1) 1715
(〉C=0), nuclear magnetic resonance spectrum δ so brass, 1.55
, 482 da of 4-isopropenyl-3,7-dimethyl-1,6-octadien-3-ol obtained as the 1.60 pre-distillate was placed in a 1' three-bottle flask and heated with an inert gas (
A rearrangement reaction was carried out by heating at an internal temperature of 170 to 180'C for 3 to 4 hours under an atmosphere of N2 or He.

The reaction solution is vacuum distilled as it is to obtain low-boiling decomposition product 2,
6-dimethylhepta-2,5-diene and a mixture of 3-isopropenyl-6-methyl-5-hepten-2-one and 3-isopropylidene-6-methyl-5-hepten-2-one, which are impurities in the raw materials, 140y were recovered. , 6,10-dimethyl-6.7, which is a rearrangement product, is extracted from the fraction with a Bp of 75 to 77°C (0.5 mmHg) as a high boiling point product.
-331q of undecadien-2-one (98% purity)
I got it. Note that this product is the product of hydrogenation with 15% Pd-C, which is the standard 6,10-dimethylundecar 2
-on and gas chromatography retention time and nuclear magnetic resonance spectrum matched.

The main products upon decomposition of 2 ozono are 4-methyl-pentene-1-al [Mass, 98, 69, 4l] and heptane-2,6-dione [Mass: 128, 110,
95,8571,58,43].

The structure was also confirmed by Example 2 Geranyl chloride 142.8y was prepared in the same manner as in Example 1.
and 162.7 q of mesityl oxide were reacted in a solution of 99.6 y of sodium hydroxide and 81.5 y of water at 40° C. in the presence of 5 da of methyltricyclohexylphosphonium chloride.

The reaction solution was poured into water and extracted with ether, washed with water, dried, and then the solvent and excess mesityl oxide were distilled off under reduced pressure. The residue 188y was vacuum distilled to Bp8O~98℃ (0.2
3-isopropenyl-6,1 as a fraction of
0-dimethyl-5,9-undecadien-2-one (5
A mixture 164y of 8%) and 3-isopropylidene-6,10-dimethyl-5,9-undecadien-2-one (42%) was obtained (yield 79.87% in terms of purity).
). This product was precision distilled to a Bp of 84-89°C (a).
3-isopropenyl-6,1 from the fraction (25 mmHg)
0-dimethyl-5.9-undecadien-2-one 7
6q193-9rC(4). 25n1mHg) 3-isopropylidene-6,10-dimethyl-5,9
47' of -undecadien-2-one and 34y of middle distillate were obtained. The structure of the product was confirmed by the following method. Infrared absorption spectrum (Crn-1) 1713 (>C
=0),1670,1640(':/C=C(),14
40,1376,1352,1153,1110,90
0 nuclear magnetic resonance spectrum δ gastric GXl4 infrared absorption spectrum (Cm-1) 1685 (〉C=0), magnetic resonance spectrum δW work 14 Then the middle distillate 34 (l and 3
-Isopropylidene-6,10-dimethyl-5,9-undecadien-2-one 47y was dissolved in the presence of 4-nitroisophthalic acid 5y at a vacuum degree of 5 mmHg and a reflux ratio of 30/1 using a precision distillation column with 50 theoretical plates. Thermal isomerization distillation was carried out under the following conditions to obtain distillate 64y.

As a result of gas chromatography analysis, this product was found to be 3-isopropenyl-6,10-dimethyl-5,9-undecadien-2-one (92%) and 3-isopropylidene-6,10-dimethyl-5,9-undecadien-2-one ( 8%). Said 3-isopropenyl-6,10-dimethyl-5,9-undecadiene-2-
The following ethynylation reaction was carried out together with On 76y. Pour liquid ammonia 1e into the 2' three-roof flask,
After adding 13y of metallic sodium, acetylene gas was blown into the reaction solution, and when the reaction mixture turned a carbon color, 140 da of 3-isopropenyl-6,10-dimethyl-5,9-undecadien-2-one was added, and then acetylene gas was added. The reaction is completed after 3 hours of bubbling.

After removing ammonia, neutralize with ammonium chloride, pour into water, and extract with ether. After drying with boronic acid, the solvent was distilled off under reduced pressure, and the residue was distilled under high vacuum.
(stomach). 3138y of 4-isoprobenyl-3,7,11-methoxidedodecar-6,10-dien-1-yn-3-ol was obtained as a fraction of 3T0rLHg). As a result of gas chromatography analysis, this product contained 1% 3-
Isopropenyl-6,10-dimethyl-5,9-undecadien-2-one and 4% 3-isopropylidene-6
, 10-dimethyl-5,9-undecadien-2-one. The structure of the product was confirmed by the following method. Infrared absorption spectrum (CwL-1) 3500,3
450 (1 nuclear magnetic resonance spectrum δ Zeng Yue 04 then 4
-isopropenyl 3,7,11-trimethyldodecar 6
, 10-dien-1-yn-3-ol 47.2f n
-Dissolved in 500 mL of hexane and partially hydrogenated in the presence of 4.7 g of 0.25% palladium-Rindler catalyst in a hydrogen stream system.

The time course of the reaction was measured using gas chromatography (PEG2O
The analysis was completed with the disappearance of the raw material.

At the same time, the reaction solution was separated to recover the catalyst, and at the same time, the solution was concentrated by distilling off the solvent under reduced pressure to obtain a residue of 45.8y. The residue was analyzed by gas chromatography, infrared absorption spectroscopy, mass spectrometry, and nuclear magnetic resonance spectroscopy, and the results showed that it was 4-isopropenyl-3,7,
11-trimethyldodecar 1,6,10-triene-3
- It became clear that it was all. The boiling point of this substance is BplO5~109C (0.09TnmHg
) It was hot. The obtained 4-isopropenyl-3,7,1
1-trimethyldodecar 1,6,10-triene-3-
All 40y was placed in a 100 mL three-bottle flask and heated at 185 to 190'C for 3 hours under a nitrogen atmosphere to carry out a rearrangement reaction. The reaction solution is vacuum distilled as it is to obtain the low-boiling decomposition product 2,6,10-trimethyl-2,5,
9-Undecatriene and 3-isopropenyl-6,0-dimethyl-5,9-undecadien-2-one and 3-isopropylidene-6,10-dimethyl-5,9-undecadien-2-one contained in the raw materials were recovered. , Bpl2O~130°C (0.17r0T
The desired rearrangement product (26.8 da) was obtained from the fraction of (tHg).

The structure of this substance was confirmed by infrared absorption spectroscopy and nuclear magnetic resonance spectroscopy. 5%-P of this
After hydrogenation with d/C to give phytone, the product obtained by reacting with vinyl Grignard reagent had gas chromatography retention time and nuclear magnetic resonance spectrum that matched those of commercially available isophytol Azusa product. Example 3 As in Example 1, 300 g (7.5 m
01) Prenyl chloride 522 in monowater 245y solution
da (5m01) and mesityl oxide 980 da (10n)
101) in the presence of a trimethylstearylammonium chlorite catalyst of 24.2 da, at a reaction temperature of 32 to 35°C.
Stir while maintaining the temperature.

The time course of the reaction is shown in Table 1. After 5 hours, the reaction was completed and the same procedure was performed to obtain 3-isopropenyl-6-methyl-5-hepten-2-one in a yield of 65% and 3-isopropylidene-6-methyl-5-hepten-2-one in a yield of 12%. I got it.

3-isopropylidene-6-methyl-5-heptene-2
-one was subjected to thermal isomerization distillation in the presence of 5y indolebutyric acid to recover 76 da of 3-isopropenyl-6-methyl-5-hepten-2-one with a purity of 98%.

This was mixed with the former and subjected to the next ethynylation step. 5
Put 21 dabs of liquid ammonia and 485 dabs of 3-isopropenyl-6-methyl-5-hepten-2-one into an e-autoclave, absorb acetylene in the presence of 2.5 dabs of potassium hydroxide, and heat to -2 to 5°C. The ethynylation reaction was carried out at

After the reaction, liquid ammonia was removed, the residue was poured into water, extracted with ether, dried with borax, the solvent was distilled off, and the residue was vacuum distilled to give 4-isopropenyl-3,7-dimethyl-6-octene. Total yield of 1-yn-3-ol from prenyl chloride (assuming 90% purity) 70%
I got it. The ethynylation product contained 0.2% of 3-isopropenyl-6-methyl-5-hepten-2-one and 1.3% of 3-isopropylidene-6-methyl-5-hepten-2-one. This was placed in a 51-3-necked flask, and 0.2% Pd was added as an n-hexane 21 solution.
Partial hydrogenation was carried out using a hydrogen stream system at room temperature in the presence of 30 da Lindlar catalyst, and 4-
Isopropenyl-3,7-dimethyl-1,6-octadien-3-ol was obtained with a yield of 5%. this thing 18
After heating at 0°C for 4 hours under a nitrogen atmosphere, the reaction solution was distilled under reduced pressure to obtain 6,10-dimethyl-6,9-undecaen-2-one in a yield of 68%. Example 4 Metallic sodium 23y was dissolved in 500 mL of liquid ammonia, and octene amount of iron chloride was added to make sodium amide. Then, a mixture of tetrahydrogeranyl chloride 176zo and mesityl oxide 196y was added dropwise, and after the dropwise addition, the mixture was further stirred for 2 hours. do.

After the reaction, ammonia is removed, neutralized with ammonium chloride, poured into water, and extracted with ether. After drying with borax, the solvent and excess mesityl oxide were distilled off under reduced pressure.
The residue was vacuum distilled to a Bp of 95-98°C (0.50Tf).
3-isopropenyl-6,10 from the fraction of UrLHg)
-dimethylundec-2-one 178.5y (yield 75
%) was obtained. As a result of gas chromatography analysis, this product contained 11% of 3-isopropylidene-6,10-dimethylundec-2-one. Next, 700 ml of N-methylpyrrolidone was placed in a 2e-autoclave, and 178.
5y was ethynylated (reaction temperature 0-5°C, reaction time 3 hours). Pour the reaction solution into water, extract with ether, wash with water,
After drying, the solvent was distilled off under reduced pressure, and the residue was distilled under high vacuum to obtain Bpl.
lO~115°C (a). 2Tf$1Hg) 4 as a fraction
173q of -isopropenyl-3,7,11-trimethyldodecar-1-yn-3-ol was obtained. As a result of gas chromatography analysis, this product contained 12.4% of 3-isopropylidene-6,10-dimethylundec-2-one.
3-isopropenyl-6,10-dimethylundecar 2
It contained 0.2% of -on. This was added as a 0.25% solution in 500ml of n-heptane in a 1e-autoclave.
Using Pd Lindlar catalyst 5y under pressure (40k9/C
Partial hydrogenation was carried out at Tl). After hydrogenation, 165y of 4-isopropenyl-3,7,11-trimethyldodecar-1-en-3-ol was obtained as a BplO 7-112°C (0.1 TmHg) fraction by the same operation. This product was subjected to a heating reaction at 180 to 185°C for 5 hours, and 6,10,14-trimethylpentadecar-6-en-2-one was obtained in a yield of 64% by the same operation. Examples 5 to 11 Various alkyl halides [■] and mesityl oxide are condensed under various conditions to produce α,β monounsaturated ketones [
[■] is thermally isomerized and distilled in some cases to β, γ monounsaturated ketone [■], and the obtained β, γ monounsaturated ketone is subjected to an ethynylation reaction under various conditions to form propargyl alcohol. This was partially hydrogenated using a Lindlar catalyst to obtain an allylic alcohol [old], and then heated to give a δ,ε monounsaturated ketone [1].

The results are shown in Table 2. Example 12 Freshly prepared metallic magnesium 27y was placed in dry tetrahydrofuran 2000rT11, and vinyl bromide 107y was reacted at a reaction temperature of 40% using a small amount of iodine as a catalyst.
It was slowly added dropwise while maintaining the temperature at ~50°C.

After the dropwise addition, the mixture was further stirred for 10 I at the same temperature to obtain vinylmagnesium bromide. Then, while cooling the internal temperature to 10'C or less, a solution of 3-isopropenyl-6-methyl-5-hepten-2-one 166y obtained by the method of Example 1 in 500 rT11 of tetrahydrofuran was slowly added dropwise. After the dropwise addition, the reaction temperature was raised to 60'C and the reaction was continued for an additional 3 hours. The reaction solution was poured into ice water, neutralized with 1N HCl, and extracted with ether. After drying with boronic acid, the solvent was distilled off under reduced pressure, and the residue was vacuum distilled to obtain 4-isopropenyl-3,7-dimethyl-1,6-octadien-3-ol in a yield of 74%. 100y of this product was distilled under reduced pressure of 20111mHg, and the distillate was introduced into a reaction tube heated to 370 to 385°C without cooling to carry out Oxy-COpe rearrangement under gas phase conditions (
The reaction product was collected in a trap cooled with dry ice. The recovered amount was 83y, and when this was analyzed by gas chromatography, 4y of the raw material was found.
-Isoprobenyl-3,7-dimethyl-1,6-octadien-3-ol has almost disappeared, and 6,10-dimethyl-6,9-undecadiene-2-
The remaining components were 2,6-dimethyl-2,5-heptadiene and methyl vinyl ketone. Reference Example 1 Liquid ammonia 1e1 and sodium 23y are placed in a 2e three-bottle flask, and acetylene gas is introduced.

Claims (1)

[Claims] 1 General formula [II] ▲ Numerical formulas, chemical formulas, tables, etc. ▼ [II] (X_1 in the formula
and X_2 are both hydrogen atoms, or one is a hydrogen atom and the other together with Z_1 represents a single bond, and Z_1 represents a single bond together with X_1 or is a lower alkoxy group, R_1 is a hydrogen atom or a lower alkyl group, X_3 and X_4 are both hydrogen atoms, or one is a hydrogen atom and the other together with Z_2 represents a single bond, Z_2 is X_3 or together with X_4 represents a single bond or is a hydrogen atom, a hydroxyl group, or a lower alkoxy group, R_2 is a hydrogen atom or a lower alkyl group, and n is O or 1). It is characterized by heating to cause a reaction. General formula [ I ] ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ [ I ] (X in the formula
1, X_2, X_3, X_4, R_1, R_2, Z_1
, Z_2 and n have the same meanings as in formula II). 2 General formula [IV] ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ [IV] (X_1 in the formula
and X_2 are both hydrogen atoms, or one is a hydrogen atom and the other together with Z_1 represents a single bond, and Z_1 represents a single bond together with X_1 or is a lower alkoxy group, R_1 is a hydrogen atom or a lower alkyl group, X_3 and X_4 are both hydrogen atoms, or one is a hydrogen atom and the other together with Z_2 represents a single bond, Z_2 is X_3 or together with X_4 represents a single bond or is a hydrogen atom, a hydroxyl group or a lower alkoxy group, R_2 is a hydrogen atom or a lower alkyl group, n is 0 or 1, and hal
o is a halogen atom) is reacted with mesityl oxide in the presence of an alkali condensing agent to form the general formula [III] ▲ Numerical formulas, chemical formulas, tables, etc. ▼ [III] (in the formula, X_1, X_2, X_3, X_4, R
_1, R_2, Z_1, Z_2 and n have the same meanings as those in formula [IV]), β, γ-
An unsaturated ketone is obtained, and the β, γ-unsaturated ketone is reacted with a vinyl Grignard reagent or partially hydrogenated after an ethynylation reaction to obtain the general formula [II] ▲There are mathematical formulas, chemical formulas, tables, etc.▼ [II] (X_1 in the formula
, X_2, X_3, X_4, R_1, R_2, Z_1,
Z_2 and n have the same meanings as those in formula [IV]) General formula [I] characterized by heating and isomerizing this allylic alcohol ▲There are mathematical formulas, chemical formulas, tables, etc.▼ [I] (X_
1, X_2, X_3, X_4, R_1, R_2, Z_1
, Z_2 and n have the same meanings as in formula [IV]).