JPH06279338A - Production of meso-(3e,7e)-5,6-bis(hydroxymethyl)-3,7-decadiene - Google Patents

Abstract

PURPOSE:To synthesize a synthetic intermediate of an attracting pheromone to injurious insects of citrus (insects of Biprorulus: Biprorulus bibax Breddin) in a high yield and in high purity. CONSTITUTION:The subject production consists of 4 processes, the first process in which 2(E)-hexene-1,4-diol is subjected to react with t-butyldimethylsilyl chloride, the second process in which the formed product is subjected to react with 3(E)-hexenoic acid, the third process in which the formed product is subjected to react with trimethylsilyl chloride to form a trimethylsilyl ether, which is subjected to react to rearrange and is hydrolyzed with an acid and the forth process in which the formed product is reduced to form meso-(3E,7E)-5,6-bis(hydroxymethyl)-3,7decadiene.

Description

Detailed Description of the Invention

[0001]

The present invention relates to cis- (1'E) -3,4- which is an attracting pheromone for citrus pests such as lemons and mandarins (stink bugs: Biprorulus bibax Breddin) that live in Australia. Meso- (3E, 7E) -5,6-bis (hydroxymethyl) -3,7-decadiene [hereinafter referred to as (A) compound, which is useful as a synthetic intermediate for bis (1'-butenyl) tetrahydro-2-furanol] May be referred to as]].

[0002]

2. Description of the Related Art Conventionally, the meso- (3
E, 7E) -5,6-bis (hydroxymethyl) -3,
Several reports have been made on the method for producing 7-decadiene. For example, method (a): 3 (E) -hexenoic acid is treated with a base (lithium diisopropylamide) and then iodine to perform an oxidative coupling reaction to obtain a succinic acid derivative, which is further reduced with a reducing agent (hydrogenation). (A) Compound synthesis method [Tetrah]
edron Letters, 33 (7), 891 ■ 894,1992], and (b)
Method: Using a Diels-Alder reaction product of butadiene and maleic anhydride as a starting material, a synthesis method of a compound (A) through 11 steps [Liebigs Ann. Chem. 1992, 1185 ■
1190] and the like have been proposed.

[0003]

However, the above-mentioned conventional method for producing the compound of the formula (A) is not always satisfactory. For example, in the method (a), a large amount of other isomer mixture is produced as a by-product. High-performance liquid chromatography separation is required to obtain the desired product, which is not suitable for mass production. Further, the method (b) has a disadvantage that it requires many steps and complicated steps, and thus has a problem to be solved.

[0004]

Therefore, the present inventors have
We have conducted intensive studies to establish a new industrially advantageous manufacturing method that can solve the above problems. As a result, by selecting 2 (E) -hexene-1,4-diol as a starting material, we have found a production method capable of synthesizing the compound (A) in good yield and good purity, and completed the present invention.

According to the invention, 2 (E) -hexene-
1,4-diol [(E) compound] was added to t-butyldimethylsilyl chloride (TBS) in an organic solvent in the presence of a base.
Cl) to form 1- (t-butyldimethylsilyloxy) -2 (E) -hexen-4-ol [(D) compound] in the first step / the (D) compound in an organic solvent, Reacting with 3 (E) -hexenoic acid in the presence of dicyclohexylcarbodiimide (DCC) (3E, 2
E ')-3-hexenoic acid 4'-(t-butyldimethylsilyloxy) -1'-ethyl-2'-butenyl [(C) compound] second step / the (C) compound is an organic solvent (3E, 7E) -5- (t-butyl) by enolization in the presence of a base, trimethylsilyl etherification with trimethylsilyl chloride (TMSCl), followed by a rearrangement reaction and subsequent hydrolysis with acid. Dimethylsilyloxymethyl) -6-hydroxycarbonyl-3,
Third step of forming 7-decadiene [(B) compound] / Meso- (3E, 7E) -5,6-bis (hydroxymethyl) by treating the (B) compound with a reducing agent in an organic solvent. The compound (A) can be easily synthesized by the production method including the fourth step of forming -3,7-decadiene [(A) compound]. Below, (A)
The first to fourth steps of synthesizing the compound will be described in detail for each step.

Production process of the first step: [(D) compound combination
Compound ] The compound (E), which is a raw material for synthesizing the compound (D), is publicly known and can be synthesized by a conventionally proposed method. Further, the method found by the present inventors, namely, propargyl alcohol and 2,3 -Reacting dihydropyran to produce tetrahydropyranyl ether, reacting the product with ethylmagnesium bromide and then reacting with propanal, 1-tetrahydropyranoxy-2-hexyne-4
-Produces the ol and then the product is added to p
-Treated with toluenesulfonic acid, 2-hexyne-1,4
-The compound (E) can be obtained by producing a diol and further reducing the product with lithium aluminum hydride.

According to the first step of the present invention, 2 (E) -hexene-1,4-diol [(E) compound] is t-butyldimethylsilyl chloride (TBSCl) in an organic solvent in the presence of a base. 1- (t-butyldimethylsilyloxy) -2 (E) -hexen-4-ol [(D) compound] can be easily synthesized by reacting with.

The reaction temperature and reaction time of this reaction are, for example, about -30 ° C to about 50 ° C, more preferably about 0 ° C.
A temperature range of about 30 ° C. to about 30 hours can be used for about 1 hour to about 24 hours. The amount of TBSCl used can be exemplified within the range of about 1.0 mol to about 1.5 mol per 1 mol of the compound (E). Specific examples of the organic solvent used in this reaction include, for example, dichloromethane, dichloroethane,
Halogenated hydrocarbons such as chloroform can be used, and the amount of these organic solvents used is preferably in the range of about 1 to about 100 parts by weight per 1 part by weight of the compound (E). Examples of the type of base used in this reaction include nitrogen-containing organic bases such as triethylamine, tributylamine, pyridine, and imidazole. The amount used is 1 mol of the compound of the formula (E). A range of about 1 mol to about 5 mol can be exemplified. This reaction is, for example, 4- (dimethylamino)
It is preferably carried out in the presence of a reaction accelerator such as pyridine (DMAP). After completion of the reaction, distillation, washing, extraction, drying,
The compound (D) can be obtained in good yield and purity by appropriately adopting an ordinary separation means such as column chromatography.

Second step production method: [(C) compound combination
According to a second step of forming the present invention, 1-(t-butyldimethylsilyloxy) -2 (E) - organic solvent hexene-4-ol [(D) Compound, dicyclohexylcarbodiimide (DCC) Reacting with 3 (E) -hexenoic acid in the presence of (3E, 2E ')-3-hexenoic acid 4'-
(T-Butyldimethylsilyloxy) -1'-ethyl-
2'-butenyl [(C) compound] can be easily synthesized.

Although the reaction time depends on the reaction temperature,
For example, in a temperature range of about 0 ° C to about 80 ° C for about 1 hour to
About 10 hours can be adopted. The preferred amount of 3 (E) -hexenoic acid used in the reaction is in the range of about 1 mol to about 2 mol per 1 mol of the (D) compound. Specific examples of the organic solvent used include halogenated hydrocarbons such as dichloromethane, dichloroethane, and chloroform, and the amount of these organic solvents used is, for example, about 1 part by weight of the compound (D). A range of about 1 to about 100 parts by weight can be exemplified. Also, D
The amount of CC used is preferably, for example, in the range of about 1 mol to about 5 mol per 1 mol of the compound (D). Also in this step, it is preferable to carry out in the presence of a reaction accelerator such as DMPA. After completion of the reaction, distillation, washing,
The compound (C) can be easily synthesized in good yield and good purity by appropriately adopting ordinary separation means such as extraction, drying and column chromatography.

Third step of production method: [(B) compound combination
According to a third step of forming the present invention, (3E, 2E ') - 3- hexenoic acid 4' - (t-butyldimethylsilyloxy) -
1'-Ethyl-2'-butenyl [(C) compound] is enolized in an organic solvent in the presence of a base, and then converted to trimethylsilyl ether with trimethylsilyl chloride (TMSCl), followed by transfer reaction, followed by acid reaction. By hydrolysis with (3E, 7E) -5- (t-butyldimethylsilyloxymethyl) -6-hydroxycarbonyl-
3,7-decadiene [(B) compound] can be produced.

The reaction temperature of the enolization reaction is, for example, about -100 ° C to about 0 ° C, more preferably about -80 ° C.
To about -50 ° C, and the reaction time may be about 0.5 hours to about 3.0 hours. Specific examples of the organic solvent used in this reaction include hexamethylene phosphoramide (HMPA) and tetrahydrofuran (TH
F), dimethoxyethane, n-hexane, toluene, benzene, diethyl ether and the like can be shown, and these solvents can be used alone or as a mixture. The amount of the organic solvent used is preferably, for example, in the range of about 1 to about 100 parts by weight relative to 1 part by weight of the compound (C). The type of base used in this reaction is, for example, lithium hexamethyldisilazide (LHMDS),
Lithium diisopropylamide, lithium tetramethylpiperazide, butyl lithium and the like,
The amount thereof used can be exemplified within the range of about 1 mol to about 2 mol per 1 mol of the compound of the formula (C). The produced enol compound can be subjected to the subsequent enol etherification reaction and transfer reaction in the same reaction system without isolation.

In the enol etherification reaction and rearrangement reaction in this step, the generated enol is converted into trimethylsilyl ether with TMSCl, and then the temperature is gradually raised to room temperature for transfer. The reaction temperature and reaction time in the step of trimethylsilyl etherification with TMSCl can be, for example, in the temperature range of about −100 ° C. to about 0 ° C. and about 1 hour to about 24 hours. Also, TMSC
The amount of 1 used is about 1 mol to 1 mol of the compound (C).
It may be in the range of about 3 mol. Then
A transfer reaction is carried out by gradually raising the temperature of the reaction system to room temperature, and after the transfer reaction, the reaction system is hydrolyzed with an aqueous solution of an inorganic acid such as hydrochloric acid to obtain (3E, 7E) -5- (t-
Butyldimethylsilyloxymethyl) -6-hydroxycarbonyl-3,7-decadiene [(B) compound] can be produced. The compound (B) can be isolated by appropriately adopting an ordinary separation means, but the reaction of the following fourth step may be carried out as it is.

Production method of the fourth step: [(A) Compound combination
According to a fourth step of forming the present invention, (3E, 7E) -5- ( t
-Butyldimethylsilyloxymethyl) -6-hydroxycarbonyl-3,7-decadiene [(B) compound] is treated with a reducing agent in an organic solvent to give meso- (3E,
7E) -5,6-bis (hydroxymethyl) -3,7-
Decadiene [(A) compound] can be easily produced.

The reaction temperature of the reduction reaction varies depending on the reaction time, but for example, in the temperature range of about -30 ° C to about 100 ° C, about 1 hour to about 24 hours can be adopted. Examples of the reducing agent used in this reaction include metal hydrides such as lithium aluminum hydride and aluminum hydride, and the amount of the reducing agent used is about 0.1 with respect to 1 mol of the compound of the formula (B). 5 mol or more, more preferably about 1
It can be exemplified in the range of about mol to about 10 mol. Further, as the kind of the organic solvent, for example, tetrahydrofuran, diethyl ether, diglyme, dimexietan, etc. can be shown, and the amount thereof is, for example, about 1 to about 100 parts by weight relative to 1 part by weight of the compound of the formula (B). The range is good.
After completion of the reaction, ordinary separation means such as distillation, washing, extraction, drying and column chromatography are appropriately adopted to obtain meso- (3E, 7E) -5,6-bis (hydroxymethyl) in good yield and purity. ) -3.7-decadiene [(A) compound] can be obtained.

It can be obtained as described above (A)
The compound lives in Australia and contains citrus pests such as lemons and mandarins (Hipoptera insects: Biprorulus b.
ibaxBreddin) attracts pheromone cis- (1 '
E) -3,4-bis (1'-butenyl) tetrahydro-
It is useful as a synthetic intermediate of 2-furanol. That is,
The compound (A) was treated with silver carbonate-Celite to give cis-
Cis- (1'E) was obtained by forming (1'E) -3,4-bis (1'-butenyl) tetrahydro-2-furanone and then reducing the product with diisobutylaluminum hydride (DIBAL). -3,4-bis (1 '
-Butenyl) tetrahydro-2-furanol.

The present invention will be described in more detail below with reference to examples.

Example 1 Synthesis of 1- (t-butyldimethylsilyloxy) -2 (E) -hexen-4-ol [(D) compound] (first step). (E) Compound 75.0 g (0.647 mol), triethylamine 78.5 g (0.776 mol), DMAP
3.95 g (32.3 mmol) and methylene chloride 1.
107 g of TBSCl (0.71 in 100 ml of mixture)
A solution of 1 mol of methylene chloride (100 ml) was added dropwise over 30 minutes while cooling with ice water. After further stirring at room temperature for 21 hours, the mixture is poured into a saturated aqueous solution of sodium hydrogen carbonate and the organic layer is separated. The aqueous layer is extracted with methylene chloride, combined with the above organic layer, washed with saturated brine, dried over magnesium sulfate, and concentrated. The obtained crude product is distilled under reduced pressure to obtain 147 g of the target compound (D). Boiling point: 86 ° C. to 87 ° C./2 mmHg Yield: 99%

[0018]

Example 2 Synthesis of 4 ′-(t-butyldimethylsilyloxy) -1′-ethyl-2-butenyl [(C) compound] (3E, 2E ′)-3-hexenoic acid (second step) ( D) Compound 69.0 g (0.300 mol), DCC
74.3 g (0.360 mol), DMAP 3.67 g
(30.0 mmol) and methylene chloride (1400 ml) under cooling with ice water 3 (E) -hexenoic acid 44.5 g
A solution of (0.390 mol) in methylene chloride (140 ml) is added dropwise over 1 hour. After stirring at room temperature for 3 hours,
Pour into dilute hydrochloric acid and extract with methylene chloride. The organic layer was washed with water, saturated aqueous sodium hydrogen carbonate solution and water again,
After drying over magnesium sulfate, concentrate. The residue is diluted with a mixed solvent of n-pentane and ether, the insoluble matter is filtered off, and the filtrate is concentrated. The obtained crude product is distilled under reduced pressure to obtain 85 g of the desired compound (C). Boiling point: 132 ° C. to 133 ° C./2 mmHg Yield: 87%

[0019]

Example 3 (3E, 7E) -5- (t-Butyldimethylsilyloxymethyl) -6-hydroxycarbonyl-3,7-decadiene [(B) Compound] (Third Step) 1.0M-LHMDS 3.3 ml of THF solution (3.3
mmol), HMPA 4.8 ml and THF 12.7 m
0.98 g of (C) compound (3.0 mmo)
l) in THF (0.5 ml) at -70 to -68 ° C,
Drip in 5 minutes. After stirring for 100 minutes at the same temperature, 0.42 g (3.9 mmol) of trimethylsilyl chloride
And triethylamine 40 mg (0.39 mmol) T
HF (1 ml) suspension is added, cooling is stopped, and the temperature is raised to room temperature. After stirring for 10 hours at room temperature, the reaction mixture is poured into dilute hydrochloric acid saturated with sodium chloride and extracted with ether. The organic layer is washed with saturated brine, dried over magnesium sulfate, and concentrated to obtain 0.93 g of the desired compound (B). Yield: 95%

[0020]

Example 4 Synthesis of meso- (3E, 7E) -5,6-bis (hydroxymethyl) -3.7-decadiene [(A) compound] (4th step) (B) compound 0.93 g (2) .8 mmol) in THF
It is dissolved in (10 ml) and added dropwise to a suspension of 0.48 g (12 mmol) of lithium aluminum hydride in THF (20 ml) under ice-water cooling for 15 minutes. Further at room temperature 3.
After stirring for 5 hours, it is poured into 1N-hydrochloric acid and extracted with ethyl acetate. The organic layer is a saturated aqueous sodium hydrogen carbonate solution,
The extract is washed with saturated brine, dried over magnesium sulfate, and concentrated. The obtained crude product is purified by silica gel chromatography to obtain 0.45 g of the desired compound (A). Refractive index (n ²¹ _D ): 1.4821 Yield: 90% (A) Compound; ¹ HNMR (300MHz, C ₆ D ₆ ) δ = 0.87 (t, J = 7.4Hz, 6H), 1.24 ■ 1.45 (m , 2H), 1.87 (d quin
t, J = 1.3,7.4Hz, 4H), 2.05 2.13 (m, 2H), 3.29 (dd, J = 6.
9,10.6Hz, 2H), 3.59 (dd, J = 4.5,10.7Hz, 2H), 5.14 (ddt, J
= 8.8,15.3,1.2Hz, 2H), 5.41 (dt, J = 15.3,6.4Hz, 2H)

[0021]

According to the present invention, 2 (E) -hexene-
From 1,4-diol, meso- (3E, 7E) -5,6-bis (hydroxymethyl) was obtained in good yield and purity in 4 steps.
-3,7-decadiene [(A) compound] can be produced.
(A) The compound inhabits Australia, and citrus pests such as lemon and mandarin (insects of stink bugs: Bipror)
cis bi which is an attracting pheromone of ulus bibax Breddin)
It is useful as a synthetic intermediate for (1′E) -3,4-bis (1′-butenyl) tetrahydro-2-furanol.

Claims (1)

[Claims] 1. 1- (t-butyldimethyl) is obtained by reacting 2 (E) -hexene-1,4-diol [(E) compound] with t-butyldimethylsilyl chloride in an organic solvent in the presence of a base. Silyloxy) -2 (E) -hexene-4-
All [(D) compound] is formed and the (D) compound is reacted with 3 (E) -hexenoic acid in the presence of dicyclohexylcarbodiimide in an organic solvent (3E, 2E ′).
-3-hexenoic acid 4 '-(t-butyldimethylsilyloxy) -1'-ethyl-2'-butenyl [(C) compound]
Is formed, and the (C) compound is enolized in the presence of a base in an organic solvent, then converted to trimethylsilyl ether with trimethylsilyl chloride, followed by a rearrangement reaction, followed by hydrolysis with an acid (3E, 7E) -5
(T-Butyldimethylsilyloxymethyl) -6-hydroxycarbonyl-3,7-decadiene [(B) compound]
And the compound (B) is treated with a reducing agent in an organic solvent to form meso- (3E, 7E) -5,6.
-A method for producing bis (hydroxymethyl) -3,7-decadiene [(A) compound].