JPS637170B2 - - Google Patents

Description

[Detailed Description of the Invention] The present invention provides a novel method for producing allyl alcohols,
In more detail, the following formula (), (In the formula, R ¹ represents a hydrogen atom, an alkyl group or alkenyl group having 1 to 10 carbon atoms that may have a substituent that does not participate in the reaction, and R ² represents a hydrogen atom or a lower alkyl group having 1 to 4 carbon atoms. , R ³ represents an alkyl group or alkenyl group having 1 to 10 carbon atoms, which may have a substituent that does not participate in the reaction, and the dotted line indicates that R ¹ and R ² combine to form a 5- to 20-membered ring. This refers to a method for producing allyl alcohols.

Many allyl alcohols represented by the formula () are useful as fragrances, pharmaceuticals, or intermediates for their synthesis, and many studies have been conducted on their production methods.

One of the basic methods for producing allyl alcohols is the isomerization of oxiranes.
Various methods are known for this purpose. For example, a recently developed method involves reacting dialkylaluminum amide with trans-2,3-dialkyloxiranes (J. Am. Chem. Soc., 1974,
96, 6513: Angew.Chem・, Ind.Ed.Engl.1978,
17, 169), method for reacting dialkyl boron trifluoromethanesulfonate (Chem. Lett,
1977, 1215), a method of reacting oxiranes derived from 5- to 7-membered cyclic olefins with strongly basic lithium amide (Synthesis, 1975, 602),
Alternatively, a two-step method using an organic selenium reagent, ie, nucleophilic substitution of oxirane with sodium phenylselenide, oxidizing the generated hydroxyselenide with hydrogen peroxide, removing phenylselenic acid, and producing the desired How to obtain allyl alcohol (J.Am.Chem.Soc., 1973, 95, 2697)
etc. are known. More recently, oxiranes are reacted with trimethylsilyltrifluoromethanesulfonate and 1,5-diazabicyclo[5,4,0]undecene-5 (hereinafter referred to as DBU) using an aromatic hydrocarbon as a solvent.
A method has been reported in which allyl alcohol with a hydroxyl group protected as trimethylsilyl ether is prepared, and the trimethyl group is removed from this in methanol using dilute hydrochloric acid or potassium fluoride to obtain the corresponding allyl alcohol (J .Am.Chem.
Soc., 1979, 101, 2738). However, these known methods have not yet been fully satisfactory in terms of stability of the reagents used, difficulties in handling, production of by-products, yield, etc.

As a result of conducting various studies on reactions that lead to allyl alcohols from oxiranes, the present inventor found that
Obtained the knowledge that 2-iodoalkoxytrimethylsilane can be quantitatively produced by reacting oxiranes with iodotrimethylsilane,
The present invention was completed by developing this.

The method of the present invention is shown by the following reaction formula.

(In the formula, R ¹ , R ² , R ³ and the dotted line have the above-mentioned meanings.) That is, in the present invention, oxiranes () are reacted with iodotrimethylsilane () to form 2-iodoalkoxytrimethylsilane (). none,
In this method, this is dehydriodized with a base and then treated with an acid to produce allyl alcohols ().

Iodotrimethylsilane (), which is the raw material of the present invention, can be prepared by adding iodine to hexamethyldisilane in a slight excess of the theoretical amount, and then mixing this mixture with about 60%
Produced by heating to ~70°C. Hexamethyldisilane is stable against heat and moisture, is non-toxic, and is easily available commercially.

To carry out the present invention, a solution of iodotrimethylsilane is prepared by dissolving iodotrimethylsilane in a solvent. Solvents are benzene, toluene,
In addition to xylene, hexane, etc., any organic solvent that does not participate in the reaction of the present invention can be used. Oxirane is added to the iodotrimethylsilane solution prepared in this manner, and the mixture is stirred and reacted. The reaction proceeds slowly, and the reaction temperature and time are usually about 1 to 5 hours at room temperature, but the reaction temperature and time are selected depending on the properties of the oxirane.

The oxiranes are represented by the above formula (), but more specifically include alkyl groups such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, amyl, and isoamyl; allyl, metaallyl, butenyl, pentenyl, hexenyl, and prenyl. , oxirane having an alkenyl group such as geranyl, cyclopentyl, cyclohexyl,
Cycloalkyl oxiranes such as cyclooctyl and cyclododecyl; cycloalkenyl oxiranes such as cyclopentenyl, cyclohexenyl, cyclooctenyl, and cyclododecenyl; and substituents that do not participate in the reaction of the present invention, such as alkoxy groups such as methoxy, ethoxy, and phenoxy, and acetyl. Examples include oxiranes having an acyl substituent such as , propionyl, and benzoyl.

Next, the 2-iodoalkoxytrimethylsilane obtained as described above is dehydriodized using a base without taking it out from the reaction system, and then treated with an acid to remove the trimethylsilyl group. Desired allyl alcohols can be easily obtained by The bases are 1,8-diazabicyclo[5,4,0]-undecene-7 (DBU), 1,5
-Diazabicyclo[4.3.0]non-5-ene (DBN) or tertiary amines such as triethylamine, tributylamine, N.N-diethylaniline; alkali metals such as sodium methoxide, sodium ethoxide, potassium butoxy; Alkoxides and the like are used, and among these, DBU is particularly suitable. That is, add DBU to 2-iodoalkoxytrimethylsilane and heat at about 70 to 80°C.
Allyloxysilane can be obtained in good yield by heating for 20 to 30 hours, followed by mineral acids such as hydrochloric acid and sulfuric acid, organic acids such as acetic acid, propionic acid, and trifluoroacetic acid, or potassium fluoride and fluoride. The desired allyl alcohol can be obtained by treatment with a compound that has a strong affinity for silicon atoms, such as cesium or tertiary ammonium fluoride.

As mentioned above, one of the features of the present invention is that the reaction including the production of the raw material iodotrimethylsilane can be carried out in one reaction vessel. That is, iodotrimethylsilane is made from hexamethyldisilane, which has stable properties and is easily available, and iodine, and oxiranes are added to it to cause the reaction. Next, a base is added to cause the reaction, followed by acid treatment. This is an industrially superior production method that is easy to operate and can yield the final target allyl alcohol in good yield. This method for producing allyl alcohols can be widely applied to the production of intermediates for pharmaceuticals, etc., and especially to the synthesis of useful fragrances.

Next, the present invention will be explained by examples.

Example 1 25.4 g (0.1 mol) of iodine was added to 15.0 g (0.102 mol) of hexamethyldisilane, and the mixture was heated at 65°C.
After heating for 15 minutes, the mixture was cooled to room temperature, and 200 ml of benzene was added thereto to prepare a benzene solution of iodotrimethylsilane. To this, at room temperature, 20.6 g of 1,2-epoxycyclohexane
(0.21 mol) was added and stirred at room temperature for 1 hour. It was confirmed by gas chromatography and thin layer chromatography that 2-iodocyclohexyloxytrimethylsilane was produced at a yield of 100%.
Then, 35.0 g (0.23 mol) of DBU was added, the temperature was raised while stirring, and the temperature was kept at 75° C. for 25 hours to complete the reaction. The ammonium salt produced was removed using a mixed solvent of hexane and ether (weight ratio 2:1) and a short column packed with silica gel. Next, after distilling off the solvent, the mixture was subjected to column chromatography packed with silica gel using a mixed solvent of benzene and hexane (weight ratio 1:3). In this way, 29.5 g of 2-cyclohexenyloxytrimethylsilane was obtained. Next, 29.5 g of 2-cyclohexenyloxytrimethylsilane was stirred in 300 ml of methanol containing 1.0 g of 1N hydrochloric acid at room temperature for 2 hours, and then distilled under reduced pressure to obtain 16.7 g of cyclohexen-3-ol with a boiling point of 64-67°C/12 mmHg. I got it. The yield for 1,2-epoxycyclohexane is
It was 81.1%.

Example 2 A benzene solution containing 0.2 mol of iodotrimethylsilane prepared in the same manner as in Example 1 was
36.4 g (0.2 mol) of cyclododecene oxide was added, and the mixture was stirred at room temperature for 1 hour. Then add this solution
35.0 g (0.23 mol) of DBU was added, and the mixture was heated and stirred at 70°C for 30 hours. After neutralizing this solution with 0.1N hydrochloric acid,
Furthermore, 200 ml of methanol containing 1.0 g of 1N hydrochloric acid was added, and the mixture was allowed to react at room temperature for 2 hours. After the reaction is complete, water
300 ml was added and stirred, and this was extracted using ether. The organic layer was washed with water, dried with anhydrous sodium sulfate, expelled the ether, and distilled under reduced pressure to a boiling point of 98-100.
29.1 g of 3-hydroxydodecene was obtained at a temperature of 15 mmHg. The yield for cyclododecene oxide is
It was 79.9%.

Example 3 25.4 g (0.1 mol) of iodine was added to 15.0 g (0.102 mol) of hexamethyldisilane, heated for 15 minutes, cooled to room temperature, and added with toluene.
200 ml was added to prepare a toluene solution of iodotrimethylsilane. This was heated to -78°C in a dry ice-methanol bath, and 14.4 g (0.2 mol) of 2,3-butylene oxide was added thereto. 30 at the same temperature
The mixture was stirred for a minute and reacted for an additional hour at room temperature. Add 35.0 g (0.23 mol) of DBU to this, stir at 80°C for 38 hours, and then proceed in the same manner as in Example 2, including decomposition with an acid catalyst, ether extraction, and distillation. 2-butenol 10.0 at 4℃
I got g. The yield based on 2,3-butylene oxide was 69.4%.

Example 4 A benzene solution containing 0.2 mol of iodotrimethylsilane prepared in the same manner as in Example 3 was heated to -78°C in a dry ice-methanol bath, and 25.2 g (0.2 mol) of cyclooctene oxide was added thereto. After stirring at the same temperature for 10 minutes, the mixture was further stirred at room temperature for 20 hours. Next, add DBU35.0g to this
(0.23 mol) was added and stirred at 80°C for 28 hours. After neutralizing this with 0.1N hydrochloric acid at room temperature, 1N
200 ml of methanol containing 1.0 g of hydrochloric acid was added, and the mixture was stirred at room temperature for 4 hours. After adding 300 ml of water and stirring, the mixture was extracted with ether, and the organic layer was washed with water and dried over anhydrous sodium sulfate. Then the solvent ether was removed,
A reaction product was obtained. This is a mixture of 3-hydroxycyclooctene and the by-product 2-hydroxybicyclo[3.3.0]octane, and instrumental analysis revealed that 3-hydroxycyclooctene was 12.3g (yield relative to cyclooctene oxide). rate of 48.8%) and 2-hydroxy [3.3.
0] It was confirmed that the product consisted of 8.1 g of octane (yield: 32.1% based on dichlorooctene oxide).

Example 5 A benzene solution containing 0.2 mol of iodotrimethylsilane prepared in the same manner as in Example 3 was heated to -78°C in a dry ice-methanol bath, and 42.4 g of 2,3-epoxygeranyl acetate was added thereto.
(0.2 mol) was added. After stirring at the same temperature for 4 hours, the mixture was further stirred at -30°C for 20 minutes. Then this
35.0 g (0.23 mol) of DBU was added and stirred at room temperature for 38 hours. After neutralizing this with 0.1N hydrochloric acid, 1N hydrochloric acid
200 ml of methanol containing 1.0 g was added and stirred at room temperature for 4 hours. After adding 300ml of water to this and stirring,
After extraction with ether, the organic layer was washed with water and dried over anhydrous sodium sulfate. The ether solvent was distilled off and distilled under reduced pressure to obtain 22.5 g of a fraction with a boiling point of 124-130°C/2 mmHg.
This product was found to be 1-acetoxy-2- by instrumental analysis.
Hydroxy-3,7-dimethylocta-3,6-
Diene and 1-acetoxy-2-hydroxy-3-
It was confirmed that it was a mixture of methylene-7-methyloct-6-ene. The ratio is 1-acetoxy-2-hydroxy-3,7-dimethylocta-
3,6-diene is 85, 1-acetoxy-2
-Hydroxy-3-methylene-7-methyloct-6-ene in a proportion of 15 and the yield relative to 2,3-epoxygeranyl acetate was 45.1, respectively.
% and 7.9%.

Claims (1)

[Claims] Linear formula () (In the formula, R ¹ represents a hydrogen atom, an alkyl group or alkenyl group having 1 to 10 carbon atoms that may have a substituent that does not participate in the reaction, and R ² represents a hydrogen atom or a lower alkyl group having 1 to 4 carbon atoms. , R ³ represents an alkyl group or alkenyl group having 1 to 10 carbon atoms that may have a substituent that does not participate in the reaction, and the dotted line indicates that R ¹ and R ³ combine to form a 5- to 20-membered ring. 2-iodoalkoxytrimethylsilane by reacting oxiranes represented by
The following formula () is characterized in that this is dehydriodized with a base and then treated with an acid. A method for producing allyl alcohols represented by the formula (wherein R ¹ , R ² , R ³ and the dotted line have the above-mentioned meanings).