CN103304456B - Convenient preparation method of 3-sulfhydryl-1-heptyl acetic ester - Google Patents
Convenient preparation method of 3-sulfhydryl-1-heptyl acetic ester Download PDFInfo
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- CN103304456B CN103304456B CN201310279505.1A CN201310279505A CN103304456B CN 103304456 B CN103304456 B CN 103304456B CN 201310279505 A CN201310279505 A CN 201310279505A CN 103304456 B CN103304456 B CN 103304456B
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Abstract
The invention relates to a preparation method of 3-sulfhydryl-1-heptyl acetic ester in a structural formula as shown in the specification. The method comprises steps of: step 1, oxidizing (E)-2-heptylene-alchohol by utilizing meta-chloroperoxybenzoic acid so as to obtain 2, 3-epoxy-1-heptanol, wherein the yield is 87%; step 2, reacting the 2, 3-epoxy-1-heptanol with thiourea under the action of titanium (IV) isopropoxide so as to obtain 2, 3-cyclosulphur-1-heptanol, wherein the yield is 78%; step 3, reducing the 2, 3-cyclosulphur-1-heptanol through utilizing sodium bisaluminumhydride so as to obtain 3-sulfhydryl-1-heptanol, wherein the yield is 85%; and step 4, reacting the 3-sulfhydryl-1-heptanol with acetic anhydride so as to obtain the 3-sulfhydryl-1-heptyl acetic ester, wherein the yield is 68%. The total yield of a whole line is 39%.
Description
The present invention relates to the preparation method of a kind of preparation method of easy 3-sulfydryl-1-heptyl acetic ester.
3-sulfydryl-1-heptyl acetic ester is the volatile component of Salvia japonica Thunb., there is the fruit aroma of tea perfume (or spice), oranges and tangerines, grape, peach sample, and the safety evaluation of U.S. FEMA (Flavour and Extract Manufacturers ' Associaion) tissue was passed through in 2007, be published in GRAS (Generally Recognized as Safe) list 23, No. FEMA is 4289.Due to 3-sulfydryl-]-heptyl acetic ester has very pleasant lasting fruity bottom note, and it has good application prospect in fruit essence.
The preparation method of the 3-sulfydryl-1-heptyl acetic ester of bibliographical information is as follows.With 3-oxo-heptanoic acid methyl esters for starting raw material, obtain 1,3-heptanediol by sodium borohydride and lithium aluminium hydride reduction, productive rate 76%; With excess acetyl chloride, primary hydroxyl is selectively converted to acetic ester, obtains 3-hydroxyl-1-heptyl acetic ester, productive rate 69%; Then with the effect of 4-toluene sulfonic acide 1,3-dimethyl-2-fluorine pyridinium salt after, react with thioacetic acid, obtain 3-acetylthio-1-heptyl acetic ester, productive rate 41%; 3-sulfydryl-1-heptanol is obtained, productive rate 92% through lithium aluminium hydride reduction; Last and excess acetyl chloride obtains 3-sulfydryl-1-heptyl acetic ester, productive rate 70%.Route overall yield 14%.The major defect of the method is that starting raw material 3-oxo-heptanoic acid methyl esters not easily obtains, and route is longer, and overall yield is low, and cost is high.
The object of this invention is to provide a kind of preparation method of easy 3-sulfydryl-1-heptyl acetic ester.It is characterized in that with (E)-2-heptene-1-alcohol for starting raw material, 2 are obtained by reacting by double bond epoxidation, 3-epoxy-1-heptanol, 2 are obtained by reacting with thiocarbamide, 3-epithio-1-heptanol, obtain 3-sulfydryl-1-heptanol through red aluminium reducing, last and acetic anhydride is obtained by reacting 3-sulfydryl-1-heptyl acetic ester.The first step reaction (E)-2-heptene-1-alcohol metachloroperbenzoic acid is oxidized, and obtains 2,3-epoxy-1-heptanol, productive rate 87%; Second step reaction 2,3-epoxy-1-heptanol reacts with thiocarbamide under the effect of tetraisopropoxy titanium, obtains 2,3-epithio-1-heptanol, productive rate 78%; Three-step reaction 2,3-epithio-1-heptanol red aluminium reducing obtains 3-sulfydryl-1-heptanol, productive rate 85%; Four-step reaction 3-sulfydryl-1-heptanol and acetic anhydride are obtained by reacting 3-sulfydryl-1-heptyl acetic ester, productive rate 68%.Route overall yield 39%.Raw material (the E)-2-heptene-1-alcohol that preparation method of the present invention uses obtains easily via the reduction of Knoevenagel condensation product (E)-2-heptenoic acid, has the advantage that route is shorter and overall yield is higher.Reaction formula is as follows:
The present invention relates to structural formula as descend shown in the preparation method of 3-sulfydryl-1-heptyl acetic ester:
3-sulfydryl-1-heptyl acetic ester
Its main process is: (E)-2-heptene-1-alcohol is oxidized with metachloroperbenzoic acid at-25 DEG C in methylene dichloride, obtains 2,3-epoxy-1-heptanol, productive rate 87%; 2,3-epoxy-1-heptanol at room temperature reacts with thiocarbamide in anhydrous tetrahydro furan under the effect of tetraisopropoxy titanium, obtains 2,3-epithio-1-heptanol, productive rate 78%; 2,3-epithio-1-heptanol obtains 3-sulfydryl-1-heptanol, productive rate 85% with red aluminium reducing in anhydrous tetrahydro furan; 3-sulfydryl-1-heptanol is obtained by reacting 3-sulfydryl-1-heptyl acetic ester at-20 DEG C, productive rate 68% with acetic anhydride in pyridine.
3-sulfydryl-1-heptyl the acetic ester prepared in the inventive method and the structure of important intermediate are all confirmed by nucleus magnetic resonance.After analytical results is attached to embodiment.
Embodiment
The preparation of (1) 2,3-epoxy-1-heptanol
Methylene dichloride (100mL) and (E)-2-heptene-1-alcohol (11.4g is added in the single port flask of 250mL, 0.1mol), in low temperature bath, be cooled to-25 DEG C, stir, add metachloroperbenzoic acid (2.76g, 0.12mol) in batches.After adding, at these-25 DEG C reaction 10h.Add 10% saturated sodium hydroxide solution after reaction terminates, and stir 30min, cancellation is reacted.With dichloromethane extraction (80mL × 3), saturated common salt water washing, anhydrous magnesium sulfate drying.Cross after filtering siccative and revolve steaming, resistates underpressure distillation, collect 55 DEG C/1.32kPa cut and obtain colourless liquid 11.3g, productive rate 87%.
1HNMR(CDCl
3)δ0.91(3H，t，J＝6.9Hz，Me)，2.26-1.50(m，4H，H-C(5)and H-C(6))，1.56(m，2H，H-C(4))，1.96(1H，t，J＝5.4Hz，OH)，2.95(2H，m，H-C(2)and H-C(3))，3.60(1H，m，H-C(1))，3.90(1H，m，H-C(1))。
13CNMR(CDCl
3)δ13.9(Me)，22.4(C(6))，27.9(C(4))，31.2(C(5))，56.0(C(3))，58.5(C(2))，61.7(C(1))。
The preparation of (2) 2,3-epithio-1-heptanols
Under the protection of nitrogen, in the four-hole boiling flask of 100mL, add 2,3-epoxy-1-heptanol (0.65g, 5mmol), thiocarbamide (0.65g, 5mmol) and anhydrous tetrahydro furan 20mL, dropwise at room temperature adds Ti (O-i-Pr)
4, stirring reaction, thiocarbamide dissolves gradually, and solution becomes clarification, continues reaction 2h.After reaction terminates, add the dilution of 10mL ether, saturated sodium bicarbonate solution cancellation is reacted.Diatomite filtration, filter cake ether and washed with dichloromethane, filtrate saturated common salt is washed, anhydrous magnesium sulfate drying.Cross after filtering siccative, revolve steaming, column chromatography (silica gel 100-200 order, V (sherwood oil): V (ethyl acetate)=15: 1) obtains product 2,3-epithios-1-heptanol 0.57g, productive rate 78%.
1HNMR(CDCl
3)δ0.91(3H，t，J＝7.2Hz，Me)，1.24-1.60(5H，m，H-C(4)-H-C(6))，1.71(1H，br，OH)，1.83(1H，m，H-C(4))，2.82(1H，m，H-C(3))，2.97(1H，q，J＝4.8Hz，H-C(2))，3.67(1H，dd，J＝12.0，4.5Hz，H-C(1))，3.89(1H，dd，J＝12.0，4.2Hz，H-C(1))。
13CNMR(CDCl
3)δ13.9(Me)，22.2(C(6))，31.2(C(5))，35.2(C(4))，40.8(C(3))，44.6 (C(2))，63.7(C(1))。
(3) preparation of 3-sulfydryl-1-heptanol
Under the protection of nitrogen, in the four-hole boiling flask of 100mL, add 2,3-epithio-1-heptanol (0.65g; 5mmol) with anhydrous tetrahydro furan 30mL; after the toluene solution (3.875mL, 12.5mmol) dropwise adding Red-Al at-10 DEG C dropwises, continue reaction 6h.Then, after adding 20mL ether dilute reaction solution, by 5% hydrochloric acid soln adjust ph to neutral, stirring reaction 20min is continued.Suction filtration, anhydrous magnesium sulfate drying.Cross after filtering siccative, revolve steaming, resistates column chromatography (silica gel 100-200 order, V (sherwood oil): V (ethyl acetate)=10: 1) is separated, and obtains colourless liquid 0.63g, productive rate 85%.
1HNMR(CDCl
3)δ0.90(3H，t，J＝7.2Hz，Me)，1.24-1.45(5H，m，H-C(4)-H-C(6))，1.39(1H，d，J＝7.5Hz，SH)，1.50(1H，m，H-C(4))，1.59-1.73(2H，m，H-C(2)and OH)，1.97(1H，m，H-C(2))，2.93(1H，m，H-C(3))，3.83(2H，m，H-C(1))。
13CNMR(CDCl
3)δ14.0(Me)，22.4(C(6))，29.2(C(5))，38.1(C(3))，39.3(C(4))，41.3(C(2))，60.8(C(1))。
(4) preparation of 3-sulfydryl-1-heptyl acetic ester
Add pyridine (25mL) and diacetyl oxide (5.5mmol, 0.56g) toward 100mL round-bottomed flask, be cooled to-20 DEG C.Stir lower slowly instillation 3-sulfydryl-1-heptanol (5mmol, 0.66g), reaction 8h.Then reaction mixture is added in dilute hydrochloric acid solution, with dichloromethane extraction (15mL × 3).Merge organic phase, anhydrous magnesium sulfate drying, cross after filtering siccative, revolve steaming, column chromatography (silica gel 100-200 order, V (sherwood oil): V (ethyl acetate)=15: 1) is separated and obtains product 3-sulfydryl-1-heptyl acetic ester 0.65g, productive rate 68%.
1HNMR(CDCl
3)δ0.90(3H，t，J＝7.2Hz，Me)，1.24-1.45(5H，m，H-C(4)-H-C(6))，1.39(1H，d，J＝7.5Hz，SH)，1.50(1H，m，H-C(4))，1.59-1.73(2H，m，H-C(2)andOH)，1.97(1H，m，H-C(2))，2.93(1H，m，H-C(3))，3.83(2H，m，H-C(1))。
13CNMR(CDCl
3)δ13.9(Me(7))，20.9(Me(C＝O))，22.4(C(6))，29.1(C(5))，37.6(C(3))，37.7(C(4))，38.8(C(2))，62.2(C(1))，171.0(C＝O)。
Claims (1)
1. the preparation method of a 3-sulfydryl-1-heptyl acetic ester, it is characterized in that with (E)-2-heptene-1-alcohol for starting raw material, 2 are obtained by reacting by double bond epoxidation, 3-epoxy-1-heptanol, be obtained by reacting 2,3-epithio-1-heptanol with thiocarbamide, obtain 3-sulfydryl-1-heptanol through red aluminium reducing, last and acetic anhydride is obtained by reacting 3-sulfydryl-1-heptyl acetic ester, and reaction formula is as follows:
。
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| CN101171326A (en) * | 2005-05-13 | 2008-04-30 | 弗门尼舍有限公司 | Thiols as flavoring ingredient |
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| CN101171326A (en) * | 2005-05-13 | 2008-04-30 | 弗门尼舍有限公司 | Thiols as flavoring ingredient |
Non-Patent Citations (2)
| Title |
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| Enantioselective Synthesis of (+)- and (-)-cis-2-Methyl-4-propyl-l,3-oxathiane and their Olfactive Properties;Wilhelm Pickenhagen et al.;《HELVETICA CHIMICA ACTA》;19841231;第67卷;947-952 * |
| 唐立伟.光学活性的3-甲硫基己醛和5(6)-丁基-1,4-二噁烷-2-酮的不对称合成研究.《中国优秀硕士学位论文全文数据库工程科技Ⅰ辑(月刊 )》.2012,(第2期),B014-108. * |
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