CN102675263B - High-yield, simple and convenient preparation method for 2-hexyl-4-acetoxyl tetrahydrofuran - Google Patents

Abstract

The invention provides a high-yield, simple and convenient preparation method for 2-hexyl-4-acetoxyl tetrahydrofuran with structural formula (I) shown in the description. The method comprises the steps of oxidizing 1-decylene-4-ol in dichloromethane by using m-chloroperbenzoic acid to obtain 1,2-expoy-4-decanol, with the yield of 89 percent; conducting ring-closure reaction to 1,2-expoy-4-decanol in methanol solution under the action of potassium carbonate to obtain 2- hexyl-4-hydroxyl tetrahydrofuran, with the yield of 96 percent; reacting 2-hexyl-4-hydroxyl tetrahydrofuran with acetic anhydride to obtain 2-hexyl-4-acetoxyl tetrahydrofuran, with the yield of 84 percent. The total yield of synthesis route is 72 percent.

Description

The preparation method of the 2 hexyl 4 acetoxy tetrahydrofuran that a kind of high yield is easy

The present invention relates to the preparation method of the 2 hexyl 4 acetoxy tetrahydrofuran that a kind of high yield is easy.

2 hexyl 4 acetoxy tetrahydrofuran is a flavor compounds with fragrant and sweet, the fragrance of a flower and fruit perfume (or spice), be one of flavor compounds that the 1st batch of being organized in that nineteen sixty-five announces of U.S. FEMA (Flavour and Extract Manufacturers ' Association) can safe edible, it is for No. FEMA 2566.But this compound in 1970 is because may exist safety problem, in the 4th batch of safe list of the flavouring agent of announcing at FEMA tissue, be removed.Again after safety evaluation, 2 hexyl 4 acetoxy tetrahydrofuran having got back to again in the 25th batch of safe list of the flavouring agent that FEMA tissue announces for 2011.Because 2 hexyl 4 acetoxy tetrahydrofuran has the strong fragrance like peach, apricot, can be widely used in various fruit essences.Also seldom there is at present the preparation method of bibliographical information 2 hexyl 4 acetoxy tetrahydrofuran.We have studied the preparation method of 2 hexyl 4 acetoxy tetrahydrofuran recently, have applied for two kinds of different preparation methods' patent.One method is take 1-decene-4-alcohol as starting raw material, through nucleophilic substitution and the dehydration three-step reaction of epoxidation, oxirane ring open loop, obtains product, and the overall yield of this synthetic route is 48% (application number 201210067609.1).Another kind method is take 1-decene-4-alcohol as starting raw material; bishydroxy, internal nucleophilic substitution pass ring and esterification four-step reaction through methylsulfonyl, two keys obtain product, and the overall yield of this synthetic route is 70% (application number 201210067613.8).

The object of this invention is to provide a kind of easy preparation method of high yield of new 2 hexyl 4 acetoxy tetrahydrofuran, compared with above-mentioned two kinds of preparation methods, preparation method of the present invention has advantages of that route is short, easy and simple to handle and productive rate is high.It is characterized in that take 1-decene-4-alcohol as starting raw material, through epoxidation, internal nucleophilic substitution pass ring and the esterification three-step reaction of two keys, obtain product.The first step reaction is that 1-decene-4-alcohol obtains 1,2-epoxy-4-decyl alcohol, productive rate 89% with metachloroperbenzoic acid (MCPBA) oxidation in methylene dichloride; Second step reaction is that 1,2-epoxy-4-decyl alcohol obtains 2-hexyl-4-hydroxyl tetrahydrofuran at effect ShiShimonoseki of salt of wormwood ring in methanol solution, and productive rate is 96%; Three-step reaction 2-hexyl-4-hydroxyl tetrahydrofuran and acetic anhydride obtain 2 hexyl 4 acetoxy tetrahydrofuran, productive rate 84%.The overall yield of this synthetic route is 72%.This synthetic method has no other bibliographical information.Reaction formula is as follows:

The present invention relates to a kind of structure suc as formula the easy preparation method of the high yield of the 2 hexyl 4 acetoxy tetrahydrofuran of (I):

Its main process is: in reaction flask, add successively methylene dichloride, 1-decene-4-alcohol, triethylamine and metachloroperbenzoic acid, obtain 1,2-epoxy-4-decyl alcohol after completion of the reaction by column chromatography for separation; 1,2-epoxy-4-decyl alcohol closes ring by intramolecular nucleophilic substitution reaction in methanol solution under the effect of salt of wormwood, obtains 2-hexyl-4-hydroxyl tetrahydrofuran; 2-hexyl-4-hydroxyl tetrahydrofuran in pyridine solution under the katalysis of DMAP with diacetyl oxide effect, obtain esterification products 2 hexyl 4 acetoxy tetrahydrofuran.

The structure of the 2 hexyl 4 acetoxy tetrahydrofuran of preparing in the inventive method and important intermediate is all confirmed by nucleus magnetic resonance or mass spectrum.Analytical results is attached to after embodiment.

Embodiment

The preparation of (1) 1,2-epoxy-4-decyl alcohol

To the 1-decene-4-alcohol and the 5.9g metachloroperbenzoic acid that add 60mL methylene dichloride, 20mmol in the round-bottomed flask of 100mL, mixture stirs 12h at-10～25 ℃.Then to reaction mixture, add saturated sodium hydrogen carbonate solution to weakly alkaline, stir 0.5～1h.Separate organic phase, water dichloromethane extraction three times, merge organic phase, then with saturated common salt washing, anhydrous magnesium sulfate drying.After rotary evaporation is concentrated, crude product, by column chromatography for separation (silicagel column, V (sherwood oil)/V (ethyl acetate)=6/1 wash-out), obtains 1,2-epoxy-4-decyl alcohol 3.06g, productive rate 89%. ¹hNMR (CDCl ₃) δ 0.87 (t, J=6.9Hz, 3H, Me (10)), 1.20～1.68 (m, 11H, H-C (5)～H-C (9) and H-C (3)), 1.85 (m, 1H, H-C (3)), 2.15 (br.S, 1H,-OH), 2.50 (dd, J=2.7, 4.9Hz, 0.5H, H-C (1), wherein a pair of diastereomer), 2.61 (dd, J=2.9, 4.9Hz, 0.5H, H-C (1), another is to diastereomer), 2.78 (dd, J=4.2, 4.9Hz, 0.5H, H-C (1), wherein a pair of diastereomer), 2.82 (dd, J=4.2, 4.9Hz, 0.5H, H-C (1), another is to diastereomer), 3.08 (m, 0.5H, H-C (2), wherein a pair of diastereomer), 3.16 (m, 0.5H, H-C (2), another is to diastereomer), 3.80 (m, 0.5H, H-C (4), wherein a pair of diastereomer), 3.87 (m, 0.5H, H-C (4), another is to diastereomer). ¹³cNMR (CDCl ₃) δ 13.9,22.5,25.4 and 25.5,29.2,31.7,37.3 and 37.6,39.4 and 39.7,46.6 and 47.0,50.2 and 50.5,69.1 and 70.1.

(2) preparation of 2-hexyl-4-hydroxyl tetrahydrofuran

By obtained 1,2-epoxy-4-decyl alcohol (15mmol) is dissolved in the methyl alcohol of 40mL, adds 3.7g salt of wormwood, under reaction mixture room temperature, stirs 5-8h.Then rotary evaporation is removed most of methyl alcohol, residuum dilute with water, and aqueous solution dichloromethane extraction three times, organic phase merges, and uses saturated common salt water washing, then uses anhydrous magnesium sulfate drying.Rotary evaporation is except after desolventizing, and crude product, by column chromatography for separation (silicagel column, V (sherwood oil)/V (ethyl acetate)=2/1 wash-out), obtains 2-hexyl-4-hydroxyl tetrahydrofuran 2.48g, productive rate 96%. ¹hNMR (CDCl ₃) δ 0.87 (t, J=6.9Hz, 3H, Me (6 ')), 1.20～1.74 (m, 11H, H-C (1 ')～H-C (5 ') and H-C (3)), 2.00 (m, 0.58H, H-C (3), main diastereomer), 2.34 (m, 0.42H, H-C (3), less important diastereomer), 3.66 (dd partly overlaps, J=4.2, 9.9Hz, 0.58H, H-C (5), main diastereomer), 3.68 (m partly overlaps, 0.42H, H-C (5), less important diastereomer), 3.78 (m, 0.42H, H-C (2), less important diastereomer), 3.83 (m, 0.42H, H-C (5), less important diastereomer), 4.01 (dd, J=4.2, 9.9Hz, 0.58H, H-C (5), main diastereomer), 4.09 (m, 0.58H, H-C (2), main diastereomer), 4.44 (m, 0.42H, H-C (4), less important diastereomer), 4.50 (m, 0.58H, H-C (4), main diastereomer). ¹³cNMR (CDCl ₃) δ 14.0 (C (6 ')), 22.5 (C (5 ')), 26.1 (C (4 '), main diastereomer), 26.2 (C (4 '), less important diastereomer), 29.2 (C (3 '), less important diastereomer), 29.3 (C (3 '), main diastereomer), 31.7 (C (2 ')), 35.4 (C (1 '), main diastereomer), 36.0 (C (1 '), less important diastereomer), 41.2 (C (3), less important diastereomer), 41.4 (C (3), main diastereomer), 72.0 (C (4), less important diastereomer), 72.1 (C (4), main diastereomer), 75.1 (C (2)), 78.2 (C (5), main diastereomer), 79.3 (C (5), less important diastereomer).

(3) preparation of 2 hexyl 4 acetoxy tetrahydrofuran

The pyridine of 1.38g 2-hexyl-4-hydroxyl tetrahydrofuran, 50mg DMAP, 2.0mL diacetyl oxide and 12mL is joined in the round-bottomed flask of 25mL, under reaction mixture room temperature, stir 12h.Then add saturated sodium hydrogen carbonate solution, mixture extracted with diethyl ether three times.Organic phase merges, and uses saturated common salt water washing, then uses anhydrous magnesium sulfate drying.Rotary evaporation is except after desolventizing, and crude product, by column chromatography for separation (silicagel column, V (sherwood oil)/V (ethyl acetate)=8/1 wash-out), obtains 2 hexyl 4 acetoxy tetrahydrofuran 1.44g, productive rate 84%. ¹hNMR (CDCl ₃) δ 0.85 (m, 3H, Me (6 ')), 1.20～1.76 (m, 11H, H-C (1 ')～H-C (5 ') and H-C (3)), 2.06 (m partly overlaps, 3H, Me-C=O), 2.09 (m partly overlaps, 0.58H, H-C (3), main diastereomer), 2.41 (m, 0.42H, H-C (3), less important diastereomer), 3.71 (m partly overlaps, 0.42H, H-C (5), less important diastereomer), 3.75 (dd partly overlaps, J=4.8, 10.5Hz, 0.58H, H-C (5), main diastereomer), 3.79 (m partly overlaps, 0.42H, H-C (2), less important diastereomer), 3.94 (m, 0.42H, H-C (5), less important diastereomer), 4.00 (m, 0.58H, H-C (2), main diastereomer), 4.13 (dd, J=4.8, 10.5Hz, 0.58H, H-C (5), main diastereomer), 5.25 (m, 1H, H-C (4)). ¹³cNMR (CDCl ₃) δ 13.9 (C (6 ')), 20.8 (Me-C=O), 22.4 (C (5 ')), 25.9 (C (4 '), main diastereomer), 26.0 (C (4 '), less important diastereomer), 29.2 (C (3 ')), 31.6 (C (2 ')), 35.0 (C (1 '), main diastereomer), 35.4 (C (1 '), less important diastereomer), 38.0 (C (3), less important diastereomer), 38.4 (C (3), main diastereomer), 72.5 (C (4)), 75.0 (C (2), less important diastereomer), 75.1 (C (2), main diastereomer), 78.2 (C (5), main diastereomer), 78.9 (C (5), less important diastereomer), 170.4 (C=O, main diastereomer), 170.6 (C=O, less important diastereomer).HRESIMS，m/z?237.14588[M+Na ⁺](Calcd.for?C ₁₂H ₂₂NaO ₃，237.14612)。

Claims (1)

1. a preparation method for 2 hexyl 4 acetoxy tetrahydrofuran, is characterized in that:

The preparation of (1) 1,2-epoxy-4-decyl alcohol

To the 1-decene-4-alcohol and the 5.9g metachloroperbenzoic acid that add 60mL methylene dichloride, 20mmol in the round-bottomed flask of 100mL, mixture stirs 12h at-10～25 ℃; Then to reaction mixture, add saturated sodium hydrogen carbonate solution to weakly alkaline, stir 0.5～1h; Separate organic phase, water dichloromethane extraction three times, merge organic phase, then with saturated common salt washing, anhydrous magnesium sulfate drying; After rotary evaporation is concentrated, crude product is by column chromatography for separation, and chromatography column is silicagel column, and elutriant is V (sherwood oil)/V (ethyl acetate)=6/1 solution, obtains 1,2-epoxy-4-decyl alcohol 3.06g;

(2) preparation of 2-hexyl-4-hydroxyl tetrahydrofuran

By obtained 15mmol1,2-epoxy-4-decyl alcohol is dissolved in the methyl alcohol of 40mL, adds 3.7g salt of wormwood, under reaction mixture room temperature, stirs 5-8h; Then rotary evaporation is removed most of methyl alcohol, residuum dilute with water, and aqueous solution dichloromethane extraction three times, organic phase merges, and uses saturated common salt water washing, then uses anhydrous magnesium sulfate drying; Rotary evaporation is except after desolventizing, and crude product is by column chromatography for separation, and chromatography column is silicagel column, and elutriant is V (sherwood oil)/V (ethyl acetate)=2/1 solution, obtains 2-hexyl-4-hydroxyl tetrahydrofuran 2.48g;

(3) preparation of 2 hexyl 4 acetoxy tetrahydrofuran

The pyridine of 1.38g2-hexyl-4-hydroxyl tetrahydrofuran, 50mg4-Dimethylamino pyridine, 2.0mL diacetyl oxide and 12mL is joined in the round-bottomed flask of 25mL, under reaction mixture room temperature, stir 12h; Then add saturated sodium hydrogen carbonate solution, mixture extracted with diethyl ether three times; Organic phase merges, and uses saturated common salt water washing, then uses anhydrous magnesium sulfate drying; Rotary evaporation is except after desolventizing, and crude product is by column chromatography for separation, and chromatography column is silicagel column, and elutriant is V (sherwood oil)/V (ethyl acetate)=8/1 solution, obtains 2 hexyl 4 acetoxy tetrahydrofuran 1.44g.