JPS6039659B2 - Novel method for producing propargyl alcohol - Google Patents

Description

[Detailed description of the invention]

The present invention relates to the general formula [1] (wherein, X and x2 are both hydrogen atoms or one is a hydrogen atom, the other together with B represents a single bond, 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 x4 are both hydrogen atoms or one of them is is a hydrogen atom and the other represents a single bond together with Z; Z2 represents a single bond together with X3 or X4; < is a hydrogen atom, a hydroxyl group or a lower alkoxy group; The present invention relates to a method for producing a novel propargyl alcohol, which is a lower alkyl group, and n is 0 or 1. Propargyl alcohol represented by general formula [1] (
Hereinafter, this will be referred to as propargyl alcohol [1])
can not only be used as a fragrance itself, but also as a fragrance,
It is a useful substance as an intermediate in the production of cosmetic bases, medicines, agricultural chemicals, etc. According to the invention, the general formula

[0] (wherein, X,, X2, X3, X4, R,, R2, Z,,
Z and n have the same meanings as in general formula [1])

Propargyl type alcohol [1] can be produced by ethynylating [0]). 8. Unsaturated ketones

[0] is the general formula [m] (in the formula,
,,X2,X3,X4,R,,R2,Z,,Z and n
has the same meaning as in general formula [1], ha
It is easily produced by reacting a halogen compound represented by (lo is a halogen atom) (hereinafter referred to as halogen compound [m]) with mesityl oxide in the presence of an alkali condensing agent. In this condensation reaction between the halogen compound [m] and mesityl oxide, the general formula [W] (wherein, X,
2, X3, X4, R, , R2, Z, , Z and n have the same meanings as in general formula [1]) Unsaturated ketone [W]) is produced in mochi, but Q.3-unsaturated ketone [W] is easily converted into P.y-unsaturated ketone.

It was found that isomerization to [0]. Therefore, at least a part of the Q.8-unsaturated ketone [W] obtained as a co-product by the condensation reaction of the halogen compound [m] and mesityl oxide is isomerized into the B.y-unsaturated ketone [b]. An additional amount of propargyl type alcohol [1] can be obtained by converting the propargyl type alcohol [1] into acetynylation reaction. Also, 3-y-unsaturated ketone

In ethynylation of [0], depending on the reaction conditions, part of the 8-y-unsaturated ketone m] undergoes reverse isomerization to Q-8-unsaturated ketone [W] during the reaction, resulting in Q-B- Unsaturated ketone [N] may be produced as a by-product, but this creation Q.Mu unsaturated ketone [W
] is also optionally an 8-y-unsaturated ketone.

After isomerizing to [0], it can be subjected to an ethynylation reaction to obtain propargyl alcohol [1]. Preferred examples of the novel propargyl alcohol [1] provided by the present invention include the following compounds. However, it is not intended to specify the three-dimensional structure of the compound having the following structural formula. 4-isoprobenyl-3-methyl-1-octyne-3-ol 4-isoprobenyl-3,7-dimethyl-1-octyne-3-ol 4-isoprobenyl-3,7-dimethyl-1-octyne-6-en-3-ol 4-isoprobenyl-3. 7-dimethyl-1-octyne-7-en-3-ol 4-isoprobenyl-3,7-dimethyl-1nonine-6-en-3-
All 4-isoprobenyl-3,7,11-trimethyl-dodecar-1-yn-3-ol 4-isoprobenyl-
3.7.11-Trimethyladecar 1-in-6.1
0-dieso-3-ol 4-isoprobenyl-3.7.
11-trimethyldodecyl-1-yne-10-en-3-ol 4-isoprobenyl-3,7-11-trimethyldodecyl-1-yne-6-en-3-ol 4-isoprobenyl-3,11-dimethyl-7-ethyltridecar 1-yne -6,10-dien-3-ol 4-isoprobenyl-3,7,11-trimethyl-dodecar-1-yne-3,11-diol 4-isoprobenyl-3,7.
11-Trimethyl-11-methoxide decar-1-yn-3-ol Among these propargyl alcohols, the following general formula [la] (wherein the dotted line indicates a double bond in one of the pupil indicated by this) is used. The group of compounds included in the group (n is 0 or 1) is, for example, isophytol, which is an intermediate for the production of vitamin E, by partially hydrogenating them and then thermally isomerizing them. However, it is particularly important because it is easily converted into the following unsaturated ketone [W], which is useful as a raw material for the synthesis of squalane, which is a base material for cosmetic products. Among the propargyl alcohols [1], compounds not included in the above general formula [la] can of course be treated in the same manner as above to lead to corresponding chain unsaturated ketones. As shown in the example below, the typical production method for terbenoid compounds conventionally used requires a long reaction process and uses expensive diketene or improbenyl ether as a C3 extender, which makes the extender a large part of the production cost. This includes the problem that the proportion of If the method of the present invention and the novel propargyl alcohol [1] produced thereby are used, as can be understood from the above explanation, compounds that are the same or similar to those produced by conventional methods can be shortened. It can be manufactured using a simple reaction process and low manufacturing cost. Next, the method of the present invention will be explained in more detail. A halogen compound [m] and mesityl oxide are reacted in the presence of an alkali condensing agent to form a P.y-unsaturated ketone.

In producing [0], methods known as methods for producing substituted ketones by a condensation reaction between an organic halogen compound and a ketone are used, such as the following method (1),

Methods [B} and {C} can be used. ■: A method in which an organic halogen compound and a ketone are subjected to a condensation reaction in the presence of an alkali amide in liquid ammonia. (Special Publications No. 40-19091 and No. 40-221)
(See Publication No. 73). 'B}: A method of reacting an organic halogen compound and a ketone in the presence of an alkaline condensing agent and an amine catalyst (or phosphonium salt catalyst) in a non-aqueous system. (Taru Publication No. 40-122251 and Japanese Unexamined Patent Publication No. 50-19
See Publication No. 6514. In addition, in the specification of Japanese Patent Publication No. 40-22251, in Example 67 showing a reaction example of prenyl chloride and mesityl oxide, 2,8-dimethyl-2,7nonadiene-4 was condensed on the methyl group side of the ketone. -one was obtained with a yield of 75%, but as a result of detailed reexamination of Example 67 by the present inventors, the yield of 2,8-dimethyl-2,7nonadione-4-one was about 5% at most. And 3-isop. The total yield of pyriden-6-methyl-5-hepten-2-one and 3-isoprobenyl-6-methyl-5-hepten-2-one was 70% or more). '○: Water-containing system with alkaline condensing agent and catalyst (
A method in which an organic halogen compound and a ketone are reacted in the presence of an amine catalyst, a quaternary ammonium salt catalyst, or a phosphonium salt catalyst. (Special Publication No. 50-137713 and Publication No. 50-1965)
(See Publication No. 14). Among these methods, the methods of ``C'' and ``C'' are preferred, and the method of ``(C)'' is particularly preferred. When comparing Method tB] and Method It has advantages such as: Ha. In carrying out the condensation reaction between the compound [m] and mesityl oxide, the same reaction conditions as in the above-mentioned known methods can be adopted, but the preferred method {B- and a brief explanation of Therefore, it is preferable to use sodium hydroxide or potassium hydroxide as the alkali condensing agent, and the amount used ranges from about equimolar to about 1 sonic mole based on the amount of halogen compound (blood) charged. Preferably about 1. Particularly preferred is a molar range of about 100 molar to about 4 times molar. It is preferable to use mesityl oxide in a range of approximately equimolar to approximately 1 sonic molar relative to the halogen compound (blood), and considering reaction efficiency, recovery, etc., it is approximately 1.5 times molar to approximately 4 times molar. It is particularly preferable that Primary amines, secondary amines, tertiary amines, salts of these amines, quaternary ammonium salts and phosphonium salts can be used as catalysts, and among these, quaternary ammonium salts and phosphonium salts are particularly preferred. Specific examples of recommended catalysts include tetrabutylammonium chloride, trimethylbenzylammonium chloride, trimethyllauryl ammonium chloride, trimethylcetylammonium chloride, trimethylstearylammonium chloride, trimethylstearylammonium bromide, 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 2.0 mol%, based on the amount of halogen compound [m] charged. The content is preferably within the range of 0 mol%. } in the above method, it is preferable to supply the alkali condensing agent to the reaction system in the form of an aqueous solution, and the concentration of the alkali condensing agent in the aqueous alkali condensing agent solution is about 4% by weight.
to about 65% by weight is preferred. In Methods and Methods, the reaction temperature is between 000 and 100
Although the temperature can be arbitrarily selected within the range of 100° C., a temperature of about 20° C. to about 70° C. is particularly preferred from the viewpoint of reaction rate and selectivity. The time required for the reaction varies depending on the type of catalyst, catalyst concentration, amount of alkali condensing agent, etc., but for example, if the amount of alkali condensing agent is approximately equimolar to the halogen compound [m], the reaction time will be approximately 10 to 30 hours. When the amount of condensing agent is about 1.5 to 44 times the mole of the halogen compound [m], about 1
The reaction is completed in ~1 field hour. In the condensation reaction between a halogen compound [m] and mesityl oxide, Q.3 monounsaturated ketone [W] is generally produced together with 8.y-unsaturated ketone [0], but both can be refined as desired. It can be easily separated by distillation. Then, when Q.8-unsaturated ketone [W] is heated in the presence of an isomerization catalyst, for example, an acidic catalyst, Q.B-unsaturated ketone [W] is isomerized to 8.y-unsaturated ketone [0]. do. 8
・Y-unsaturated ketone [0] is Q-8 monounsaturated ketone [W
], so only the 8-y-unsaturated ketone [B] is continuously extracted by heating and distilling a mixture of both under the isomerization reaction conditions of the Q-8 monounsaturated ketone [W]. It is also possible. However, from the viewpoint of reaction efficiency, it is preferable to increase the production ratio of 8·y-unsaturated ketone [0]/Q·8-unsaturated ketone [W] in the condensation reaction between the halogen compound [m] and mesityl oxide. According to the research of the present inventors, c. When the reaction temperature is high in the condensation reaction between Gen compound [m] 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 a,y-unsaturated ketone once generated [0] is reverse isomerized to Q.3-unsaturated ketone [W] in the system. For example, 5.0 moles of prenyl chloride and 10 moles of mesityl oxide are mixed in a 55% by weight aqueous solution of 7.5 moles of sodium hydroxide in the presence of 24.2 moles of trimethylstarylammonium chloride.
When the reaction is carried out at 2 to 35°C, the reaction time is 1. The conversion rate of prenyl chloride in hours was 55%, and the production ratio of 3-isoprobenyl-6-methyl-5-hepten-2-one to 3-isopropylidene-6-methyl-5-hepten-2-one was 9:10. Yes, but 3. After hours, the conversion rate of prenyl chloride was 84%, and the self-generation ratio was 7.
After 5 hours, the conversion rate of prenyl chloride was 93%, but the production ratio was 23%. Therefore, stopping the condensation reaction when the conversion rate of the halogen compound [m] reaches about 70 to 80% is effective in increasing the reaction efficiency of the condensation reaction. In addition, Q.
8-unsaturated ketone [W] to 3-y-unsaturated ketone [0
] When considering distillation separation after isomerization or distillation separation at the same time as isomerization, 8.
It is preferable to use an acid having a boiling point higher than that of the y-unsaturated ketone [b], and examples of such acids include benzenesulfonic acid, p-toluenesulfonic acid,
Aliphatic or aromatic sulfonic acids such as lauryl sulfonic acid, p-tolylic acid, 4-nitro-m-tolylic acid, 4
- monocyclic, aromatic or alicyclic monocarboxylic, dicarboxylic or polycarboxylic acids, which may contain foreign atoms, such as hydroxybenzoic acid, vanillic acid, 4-nitroisophthalic acid, cyclohexanecarboxylic acid, or adipic acid; Saturated or unsaturated aliphatic or heteroaliphatic monocarboxylic acids, dicarboxylic acids which may be hydroxylated and/or phenyl substituted, such as 1,2-dihydroxystearic acid, pendylic acid, p-nitrocinnamic acid, diglycolic acid Examples include acids or polycarboxylic acids, aliphatic or aromatic amino acids such as indolebutyric acid and 1,2-diaminocyclohexanetetraacetic acid, or inorganic acids such as metaphosphoric acid and phenylphosphinic acid. The amount of acidic catalyst varies depending on the type, but for example, when using sulfonic acids, it is 0.01 to 0.1 mol% based on Q.6 monounsaturated ketone [W], and when using other carboxylic acids. is 0.1 for Q・3-unsaturated ketone [W]
A concentration of ~20 mol %, particularly preferably about 4-8 mol %, is used. The isomerization reaction temperature is about 80q○ to about 200q
Temperatures up to 0.00 are good. The ethynylation of the 8-unsaturated ketone [0] can be carried out using methods and conditions conventionally used for the ethynylation of ketones. Conventionally used ethynylation methods include the following methods. 'a}: A method of ethynylation using a Grignard reagent. (The ketone is treated with ethynylmagnesium halide, which may be generated in situ, in tetrahydrofuran or other suitable solvent). {b}: A method in which acetylene is reacted with an alkali metal or alkaline earth metal such as sodium, potassium, or calcium in liquid ammonia to form acetylide, and this is reacted with a ketone. 'c': Reacts acetylene and ketone in the presence of strong alkali metal compounds such as potassium hydroxide, potassium alkoxide, and sodium amide in a polar solvent (e.g. N-N-dimethylformamide, dimethylsulfoxide, N-methylpyrrolidone, etc.) How to do it. '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. Although method {a' can be used to synthesize a small amount of propargyl alcohol [1], it is not suitable for large-scale operation. Since method b uses a large amount of alkali, it involves reverse isomerization from 8.y-unsaturated ketone [n] to Q.8 monounsaturated ketone [W] during the ethynylation reaction. For example, 3-isoprobenyl-6-methyl-5-heptene-2 is formed by forming acetylide by making 69 yen of metallic sodium exist in liquid ammonia and blowing acetylene gas into it.
When the ethynylation reaction was carried out by adding 500 g of -one (purity 99%), the composition of the product was 5% of 3-isoprobenyl-6-methyl-5-hepten-2-one, 3-isopropylidene-6-methyl-1, 5-heptene-2-on-1
0%, 4-isoprobenyl-3,7-dimethyl-1-octyne-6-en-3-ol 85%. Method{
c} and method 'When the ethynylation reaction is carried out in the presence of a catalytic amount of alkali IJ, 8.y-unsaturated ketone [0]
Although it involves some degree of reverse isomerization from Q.
The methods of 'c' and (d) are particularly preferred. When carrying out the ethynylation reaction by the methods of 'c' and {d', sodium hydroxide or potassium hydroxide is used industrially for the compound [D] to be used. ], it is preferable to use 0.1 to i% by weight, particularly preferably 0.5 to 3% by weight, at a reaction temperature of -50 to 5°C.When compound (0) is ethynylated, Considering that compound (W) is produced as a by-product regardless of the amount and that compound (N) and compound (1) can be separated by distillation, compound (m) and mesityl oxide are condensed. The mixture of compounds (0) and (W) obtained by the above process is directly subjected to an ethynylation step, followed by distillation separation to obtain compound (1), and at the same time, the recovered compound (W) is subjected to an isomerization step. The novel propargyl-type terbene alcohol represented by the general formula (1) can be produced by a combination of known reactions, but it can also be used in fragrances. The Carroll rearrangement reaction using diketene, which has been the mainstream C-3 extender in terbenoid synthesis for the past several decades, or the Claise gene position reaction using improbenyl ether, provides new materials for use as C-3 extenders. It is an important compound that can solve the problem of production cost.It will be explained in detail in Examples and Reference Examples below.Example 1 Mesityl oxide in a solution of 600 ml of sodium hydroxide and 490 ml of water. Mei 0 yen, prenyl chloride 520 yen,
Add 25 minutes of trimethylstearylammonium chloride and perform a water bath (reaction temperature rises to 70°C).
The reaction was completed after 2 hours. The reaction solution was poured into water, extracted with ether, washed with water, and dried. After the solution was distilled off under reduced pressure, the remaining 1,250 ml was distilled to recover excess mesityl oxide, and 3-isoprobenyl-6-methyl-5-hepten-2-one and 3-isoprobenyl-6-methyl-5-hepten-2-one and 3
A 2.5:1 mixture of isopropylidene-6-methyl-5-hepten-2-one was obtained (purity 96.4).
%). The purity of prenyl chloride used was 83.71.
%, 3-isoprobenyl-6-methyl-
The yield of 5-hepten-2-one was 60%, and the yield of 3-isopropylidene-6-methyl-5-hepten-2-one was 24%. When the above mixture is distilled and separated using a Yamayasu precision distillation column with 3 theoretical plates, 3-isoprobenyl-6-methyl-5-hepten-2-one with bp32-340 ((0.2 Hg)) is separated. , 3-isopropylidene-6-methyl-5-hepten-2-one was obtained from crabs with a temperature of 35 to 0.2 degrees Celsius (0.2 kite Hg).These structures were confirmed by the following method. -1) 1714 (>C=○), 1 mouse 2 (>
C=C), 1445, 1378, 1353, 1153
900 nuclear magnetic resonance spectrum (incCI4:ppm
) 1.57, 1-9 each S, same day, CH3-1.9ku s, Chihito, 2.03-2.4um, 2nd,
1 CH2-3.07, t, IH, 4.8fu 4.89
each s, 2 days, =CH24.9t, IH, infrared absorption spectrum (arc-1), 1 skin > C = ○),
1615 (>○=C), 1440, 137fu 1350
, 1278 1202, 1170 97 93fu 8
50 nuclear magnetic resonance spectrum (inCC14:ppm) 1
．． 62, 1.701.75, each s, 12th, C
H3-2.05 s, Chihito, 2, total d, but one lump - 4.97, t, IH, obtained 3-isopropylidene-6-methyl-5-hepten-2-one 130 t is 7th evening tranS-1・2-
It was put into the bottom of a precision distillation column with 5 theoretical plates together with cyclohexanedicarboxylic acid, and the vacuum degree was 30 Hg and the reflux ratio was 3.
Distilled at 0/1 to obtain 107 pieces of crab matter. As a result of gas chromatography analysis, this product was found to be 3-isoprobenyl-6-methyl-5-hepten-2-one (
94%), 3-isopropylidene-6-methyl-5-hepten-2-one (6%). 3 above
-Isoprobenyl-6-methyl-5-hepten-2-one was used to carry out the following ethynylation reaction. Three volumes of liquid ammonia were placed in a three-necked flask, 70 volumes of metallic sodium was added, and acetylene gas was blown into the flask. When the reaction solution turned gray, the blowing of acetylene gas was stopped, and 517 g of 3-isoprobenyl-6-methyl-5-hepten-2-one was added, followed by blowing acetylene gas and reacting for 3 hours. After removing ammonia, the mixture was neutralized with ammonium chloride, poured into water, and extracted with ether. After drying with glass powder, the solvent was removed under reduced pressure. The residue was distilled under reduced pressure to 59-61°C (0.5 Cape H).
519 fractions of g) were obtained. This is 3-isoprobenyl-6-methyl-5-hepten-2-one (2%),
3-isopropylidene-6-methyl-5-heptene-2
-one (8%), 4-isoprobenyl-3,7-dimethyl-6-octen-1-yn-3-ol (90%). The structure of the product was confirmed by the following method. Infrared absorption spectrum (arc-1) 3440 (1OH
), 3300, 2120, 1640, 1450, 137
8, 1128, 1030, 900 nuclear magnetic resonance spectrum (incCI4:ppm) 1.40, s, 3 days, 1.6
S, Mother's Day, CH3-1.72, 1.73each s, 3rd, 2.00-2
．． 47, m, 3 days, 2.3 us, IH, -C3CH Ca4.83-5.00, m, 9 days, =CH-, =C ratio Example 2 Geranylchlora in the same manner as Example 1 id 1
42.8 ml of mesityl oxide and 162.7 ml of mesityl oxide were reacted for 4 hours in the presence of 5 ml of methyltricyclohexylphosphonium chloride in a solution of 99.6 ml of sodium hydroxide and 81.5 ml of water. The reaction solution was poured into water and extracted with ether. After washing with water and drying, the solvent and excess mesityl oxide were distilled off under reduced pressure. Vacuum distillation of one residue was carried out to a temperature of bp80~pseudo℃(0.2℃H).
g) 3-isoprobenyl-6,10-dimethyl-5,9-undecadien-2-one (58%) and 3-isopropylidene-6,10-dimethyl-5.
1M mixture of 9-undecadien-2-one (42%)
I got the evening. (Yield 79.87% based on purity). Precision distillation of this product gives a BP of 84 to 8900 (0.25 skin H).
From the fraction of g), 3-isoprobenyl-6,10-dimethyl-5,9-usodecadien-2-one was extracted for 76 days, bp
From the crab fraction of 93-970 (0.25 Hg), 47 volumes of 3-isopropylidene-6,10-dimethyl-5,9-undecadien-2-one and 34 volumes of middle distillate were obtained. The structure of the product was confirmed by the following method. Infrared absorption spectrum (arc-1) 1713 (>C=○), 167o,
164o (>C=C<), 1440, 1376, 135
2, 11531110, 900 nuclear magnetic resonance spectrum (
inCC14:ppm) 1.53 1.57, 1.6 Reach s, 12th, CH3-Ca. 1.92-2.
0 m, 4 days, -CH2C ratio -1.95 s, 3 days,
Ca. 2.05-2.40, m, 2 days, 1CH2-3.
0fu t, IH, 4.85 4.87, each s,
2 days, 2 CH25.00, t, 2 days, =CH-Infrared absorption spectrum (Ki-1) 1 total 5 (>C=○), , 6, 5
(>C=Cku), 1440, 1375, 1351, 12
00117〇97&850,830 nuclear magnetic resonance spectrum (IncCI4:ppm)]. 5 pieces 1.9 e
ach s, Soichi, CH3-1.691.7fu eac
h s, Mother's Day, CH3-Ca. 1.95~2.1 stop m
, Mountain day, 1 CH2C Buddha 1 2.04 s, 3 days, 2.89
d, 2 days, 1C Koichi 4.99 t, 2 days, =CH- Next, the intermediate crab portion 34 and 3-isopropylidene-6
・10-dimethyl-5,9-undecadien-2-one (47 g) was mixed in the presence of 4-nitroisophthalic acid (5 g) using a precision distillation column with a variable number of theoretical plates, under the conditions of a vacuum degree of 5 Hg and a reflux ratio of 30/1. Isomerization distillation was then carried out to obtain 64 pieces of crab matter. Gas chromatographic analysis of this product revealed that it was 3-isoprobenyl-6,10-dimethyl-5,9-undecadien-2-one (92%) and 3-isoprobenyl. It was a mixture of pyriden-6,10-dimethyl-5,9-undecadien-2-one (8%). Said 3-isoprobenyl-6,10-dimethyl-5,9-undecadiene-2-
The following ethynylation reaction was carried out in conjunction with On 76. 2
After putting 1 night of liquid ammonia into the three-layer flask and adding 13 times of metallic sodium, acetylene gas was blown into the flask, and when the reaction solution turned gray, 3-isoprobenyl-
140 g of 6,10-dimethyl-5,9-undecadien-2-one was added, and acetylene gas was further blown in for 3 hours to complete the reaction. After removing ammonia, neutralize with ammonium chloride, pour into water, and extract with ether. After drying with Bositol, the solvent was distilled off under reduced pressure, and the residue was distilled under high vacuum to give a bp of 120 to 125.
138# of 4-isoprobenyl-3,7,11-trimethyldodecar-6,10-dien-1-yn-3-ol was obtained as a crab fraction of qo (0.3 side Hg). As a result of gas chromatography analysis, this product contained 1% of 3-isoprobenyl-6,10-dimethyl-5,9-undecadien-2-one and 4% of -isopropylidene-6,10-dimethyl-5,9-undecadien-2-one. It was. The structure of the product was confirmed by the following method. Infrared absorption spectrum (arc-1) 3500, 3450 (1OH
), 3290, 1630, 1442, 1373, 112
5, ]02fu 942, 92u 895 nuclear magnetic resonance spectrum (incCI4:ppm) 1.40 s, 9 days,
CH3-1.531.9〆1.7fu s, 12th, CH
31 Cal. 87-2.50 m, 7 days, -CH2CH
2-, 2.30, s, IH, 1C...CHCa4-70~
5.15 m, Mountain day, =CH2, =CH- Example 3 Same as Example 1, 300 m of sodium hydroxide (7.8 mo
l) - In a solution of 245 kg of water, 522 kg of prenyl chloride (9 hol) and 980 ml of mesityl oxide (IQho)
1) is reacted in the presence of 24.2 kg of trimethylstearylammonium chloride catalyst while maintaining the reaction temperature at 32 to 35 qo. The time course of the reaction is shown in Table 1. After 5 hours, the reaction was completed, and the same operation was performed to obtain 3-isoprobenyl-6-methyl-5-hepten-2-one in a yield of 65% and 3-isopropylidene-6-methyl-5-hepten-2-one in a yield of 65%. It was obtained with a yield of 12%. 3-isopropylidene-6-methyl-hepten-2-one was heated and isomerized in the presence of indolebutyric acid for 5 days to obtain 3-isopropylidene-6-methyl-5-hepten-2-one with a purity of 98%. I collected the evening. This was mixed with the former and subjected to the next ethynylation reaction. 5. In the autoclave, add liquid ammonia 2 and 3.
485 ml of isoprobenyl-6-methyl-5-hepten-2-one was added, and acetylene was absorbed in the presence of a catalyst of 2.5 ml of potassium hydroxide to carry out an ethynylation reaction at -2 to 5°C. After the reaction, liquid ammonia was removed, the residue was poured into water, extracted with ether, dried over Bowel's salt, the solvent was distilled off, and the residue was vacuum distilled to give 4-isoprobenyl-3,7-dimethyl-6-octene. -1-yn-3-ol was obtained in a total yield of 70% from prenyl chloride (90% purity). The ethynylated product contains 0.2% of 3-isoprobenyl-6-methyl-5-hepten-2-one and 1.0% of 3-isopropylidene-6-methyl-5-hepten-2-one.
It contained 3%. Table 1 Example 4 Dissolve 23 tons of metallic sodium in 500 liquid ammonia, add a catalytic amount of iron chloride to make sodium amide, and then dropwise drop a solution of 176 tons of tetrahydrogeranyl chloride and 196 tons of mesityl oxide. After the addition, the mixture was heated for an additional 2 hours. After the reaction, ammonia is removed, neutralized with ammonium chloride, poured into water, and extracted with ether. After drying with glass salt, the solvent and excess mesityl oxide were distilled off under reduced pressure, and the residue was distilled under vacuum to obtain 3-isoprobeni 178.5 units of 6,10-dimethylwandec-2-one (yield 75%) were obtained. As a result of gas chromatography analysis, this product contained 11% of 3-isopropylidene-6,10-dimethylundec-2-one. Next, 700% of N-methylpyrrolidone was placed in a 1-autoclave, and 3-isoprobenyl-6.
178.5 ml of 10-dimethylundecane-2-one was ethynylated (reaction temperature 0-5°C, reaction time 3 hours). The reaction solution was poured into water and extracted with ether. After washing with water and drying, the solvent was distilled off under reduced pressure and the residue was distilled under high vacuum to obtain bpllo~115.
qo (Hg on the 0.2 side) fraction, 173 pieces of 4-isoprobenyl-3,7,11-trimethyldodec-1-yn-3-ol were obtained. As a result of gas chromatography analysis, this product contained 0.2% of 3-isoprobenyl-6,10-dimethylundec-2-one and 12% of 3-isopropylidene-6,10-dimethylundec-2-one.
It contained 4%. Examples 5 to 11 Various alkyl halides [m] and mesityl oxide are condensed under various conditions, and the Q.8-unsaturated ketone [W] created is, in some cases, a B.y-unsaturated ketone.

[0] was subjected to thermal isomerization distillation, and the obtained 8-y-unsaturated ketone was subjected to ethynylation reaction under various conditions to obtain propargyl type alcohol [1]. The results are shown in Table 2. Ship reference example 1 4-isoprobenyl-3.7 obtained by the method of Example 1
-dimethyl-6-octene-1-yne → 3-ol 50
The solution was dissolved in 1.5% of n-hexane, and a hydrogenation reaction was carried out using a streamer at room temperature and pressure using 25% of 0.25% Lindlar catalyst. The time course of the reaction is analyzed by gas chromatography (M of PEG2, 150°C), and the reaction is terminated after confirming the disappearance of the raw material propargyl type alcohol. Separate the catalysts,
The solvent of the filtrate is removed under reduced pressure, and the residue is distilled under vacuum.
482 tons of 4-isoprobenyl-3,7-dimethyl-1,6-octadien-3-ol were obtained as a crab fraction from 55 to 59 o'clock (0.4 side Hg). The residue was again subjected to high vacuum distillation to obtain 12 fractions with a BP of 77 to 82°C (0.15 Hg). The following analysis revealed that this product was 6,10-dimethyl-6,9-undecadien-2-one. Infrared absorption spectrum (arc-1) 348
0 (-OH), 1638 (>C=C), 1450, 1
375, Group 9, 922, 896 nuclear magnetic resonance spectra (
incCI4:ppm) 1.13 s, 9 days, CH3-
1.53 1.62, 1.60broad s, arrived in Japan,
C ratio-fCal. 90-2.20, m, 3 days, -CH2
1CH--Ca4.60-5.02, m, 4 days, 5.1
2, dd, IH, 5.8F dd, IH, 1CH= Infrared absorption spectrum (skin-1) 1715 (>C=○)
, 1675 (>C=Cku), 1445, 1360, 11
58, 1107, Nadafu 935 827 Nuclear magnetic resonance spectrum (incCI4:ppm) 1.5fu 1.6〇 e
ach s, 9th, CH3-Cal. Clothes ~2.4um
, Mother's Day, 1CH2CH2CH2-1.96 s, Chihito,
2.59 t, 2 days, 5.5 stops t, 2 days, =CH- 4-Isoprobenyl-3,7-dimethyl-1,6-octadien-3-ol A heating isomerization reaction was carried out at an internal temperature of 170 to 180° C. for 3 to 4 hours under an inert gas (N2 or He) atmosphere. The reaction solution was vacuum distilled as it was, and the decomposition product 2, which has a low aliment content, was obtained.
・6-dimethylhepta-2,5-ene and impurities in the raw materials, 3-isoprobenyl-6-methyl-5-hepten-2-one and 3-isopropylidene-6-methyl-
140 days of a mixture of 5-hepten-2-one was recovered, and 331 days of 6,10-dimethyl-6,9-undecadien-2-one, a rearrangement product, was collected from the fraction with bp75 to 770 (Hg on the 0.5 side) as a high boiling product. (purity 98%) was obtained.
The total yield from 4-isoprobenyl-3,7-dimethyl-6-octen-1-yn-3-ol (90% purity) was 74.1%. Reference example 2 In order to protect the hydroxyl group in reference example 1, 4-
Isoprobenyl-3,7-dimethyl-1,6-octadien-3-ol is reacted with an equimolar amount of trimethylchlorosilane in pyridine to form 4-isoprobenyl-3.
22.5 7-dimethyl-3-trimethylsiloxy-1,6-octadiene was obtained, which was reacted for 3 hours at 18 pC in an inert gas atmosphere.The reaction solution was vacuum distilled to give a bp of 81-8300 ( 0.2
21.0 of the rearranged product 6,10-dimethyl-2-trimethylsiloxy-2,6,9-endecatrene was obtained as a fraction of 5-side Hg). (Yield 95%). The structure of the product was confirmed by the following method. When the product was reacted for 1 hour in CI, 6,10-dimethyl-6,9-undecadien-2-one was quantitatively obtained. Infrared absorption spectrum (Ken-1) 1635
, 1448, 1372, 1260, 1252, 1120
, 1043, 922, 882, 842 nuclear magnetic resonance spectrum (incCI4:ppm) 1.50 1.62ea
ch s 12th, CH3-Cal. 93-2.15
m, 4th, -CH Yuhi 2-i l2, Hiro t, but Go upper day 2 "Jin"

Claims (1)

[Claims] 1 General formula [II] ▲ Numerical formulas, chemical formulas, tables, etc. ▼ (In the formula, both X_1 and X_2 are hydrogen atoms, or one is a hydrogen atom and the other is combined with Z_1 represents a single bond, Z_1 together with X_1 or X_2 represents a single bond or is a hydrogen atom, a hydroxyl group, or a lower alkoxy group, R_1 is a hydrogen atom or a lower alkyl group, and X_3 and X_4 are both hydrogen or one is a hydrogen atom and the other together with Z_2 represents a single bond, Z_2 is X
together with _3 or 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 0
General formula [I] ▲There are mathematical formulas, chemical formulas, tables, etc.▼ (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 in general formula [II]). 2 General formula [III] ▲There are mathematical formulas, chemical formulas, tables, etc.▼ (In the formula, X_1 and X_2 are both hydrogen atoms, or one is a hydrogen atom and the other together with Z_1 represents a single bond, Z_1 together with X_1 or X_2 represents a single bond or is a hydrogen atom, a hydroxyl group or a lower alkoxy group, R_1 is a hydrogen atom or a lower alkyl group, and X_3 and X_4 are both hydrogen atoms or one of them; is a hydrogen atom, the other represents a single bond together with Z_2, and Z_2 is X
together with ^3 or 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 halo is a halogen atom) is reacted with mesityl oxide in the presence of an alkali condensing agent to form a compound of the general formula [II ] ▲There are mathematical formulas, chemical formulas, tables, etc.▼ (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 in general formula [III]), and ethynylated the β/γ-unsaturated ketone. do. General formula [I] ▲There are mathematical formulas, chemical formulas, tables, etc.▼ (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 in general formula [III]). 3 General formula [III] ▲There are mathematical formulas, chemical formulas, tables, etc.▼ [In the formula, X_1 and X_2 are both hydrogen atoms, or one is a hydrogen atom and the other together with Z_1 represents a single bond, Z_1 together with X_1 or X_2 represents a single bond or is a hydrogen atom, a hydrogen group, or a lower alkoxy group, R_1 is a hydrogen atom or a lower alkyl group, and 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
together with _3 or 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 halo is a halogen atom) is reacted with mesityl oxide in the presence of an alkali condensing agent to form a compound of the general formula [II ] ▲There are mathematical formulas, chemical formulas, tables, etc.▼ (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 in general formula [III]
Co-produced or by-produced in the step of ethynylating the γ-unsaturated ketone and in one or both of the above two steps
General formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (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 in general formula [III]) General formula [I] comprising a step of isomerizing to a saturated ketone and subjecting the β/γ-unsaturated ketone obtained in the isomerization step to an ethynylation reaction Yes▼ (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 in general formula [III]).