CN104030951B - A kind of preparation method of easy 2-sulfydryl-4-enanthol - Google Patents
A kind of preparation method of easy 2-sulfydryl-4-enanthol Download PDFInfo
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- CN104030951B CN104030951B CN201410292674.3A CN201410292674A CN104030951B CN 104030951 B CN104030951 B CN 104030951B CN 201410292674 A CN201410292674 A CN 201410292674A CN 104030951 B CN104030951 B CN 104030951B
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Abstract
The present invention relates to the preparation method of structural formula 2-sulfydryl-4-enanthol as follows:
the method step: the first step reaction butyraldehyde and allylmgcl obtain 1-heptene-4-alcohol by grignard reaction, productive rate 87%; Second step reaction 1-heptene-4-alcohol with metachloroperbenzoic acid oxidation, obtains 1,2-epoxy-4-enanthol, productive rate 92% in methylene dichloride; Three-step reaction 1,2-epoxy-4-enanthol reacts with thiocarbamide under the effect of tetraisopropoxy titanium, obtains 1,2-epithio-4-enanthol, productive rate 80%; Four-step reaction 1,2-epithio-4-enanthol in tetrahydrofuran (THF) through LiAlH
42-sulfydryl-4-enanthol is obtained, productive rate 84% after reduction.
Description
The present invention relates to a kind of preparation method of easy 2-sulfydryl-4-enanthol.
Multi-functional group thiol's compounds has the low and odour characteristics outstanding feature of fragrance threshold value, is extensively present in various food, is the fragrant composition of important volatility of numerous food product.In these multi-functional group thiol's compounds, a lot of Sulfur-containing flavors containing 1,3-Yang Liu functional group have the fragrance of tropical fruit, vegetables, and therefore 1,3-Yang Liu functional group is called as " the raw fragrant group (olfacophore) " of this kind of fragrance, as follows:
There is a lot of bibliographical information 1 in recent years, the natural existence of Sulfur-containing flavor, aroma characteristic, preparation method etc. of 3-Yang Liu functional group, as 3-sulfydryl-1-hexanol and derivative, 3-sulfydryl-1-heptanol and derivative thereof, 3-sulfydryl-2-methyl-1-pentene alcohol, 4-sulfydryl-2-enanthol and derivative thereof etc.The Sulfur-containing flavor of increasing 1,3-Yang Liu functional group have passed the safety evaluation of FEMA tissue, and entering into can the spices list of safe edible.2-sulfydryl-4-enanthol belongs to this kind of Sulfur-containing flavor containing 1,3-Yang Liu functional group.Naturally be present in the volatile component of big capsicums, there is fruit perfume (or spice), tropical fruit, piscidia, Nasturtium officinale and vegetable aroma, be 2013 just by the safety evaluation of U.S. FEMA (FlavourandExtractManufacturers ' Association) tissue, be published in GRAS (GenerallyRecognizedasSafe) list 26, No. FEMA is 4733.
The preparation method of the 2-sulfydryl-4-enanthol of bibliographical information is as follows.With 3-oxo ethyl hexanoate for starting raw material, hydrolysis obtains 3-oxo caproic acid in the basic conditions; Then 2-hepten-4-one is obtained with acetaldehyde by aldol reaction; Thioacetic acid and 2-hepten-4-one, by Isosorbide-5-Nitrae-conjugate addition reaction, obtain 2-acetylthio-dipropyl ketone; 2-sulfydryl-4-enanthol is obtained finally by lithium aluminium hydride reduction.The major defect of this preparation method is that starting raw material is more expensive, and the aldol reaction productive rate of second step 3-oxo caproic acid and acetaldehyde is low, only has about 30%.
The object of this invention is to provide a kind of preparation method of easy 2-sulfydryl-4-enanthol.It is characterized in that obtain 1-heptene-4-alcohol by grignard reaction, then obtain 1,2-epoxy-4-enanthol by epoxidation reaction, epoxide and thiocarbamide are obtained by reacting 1,2-epithio-4-enanthol, through LiAlH with butyraldehyde and chlorallylene for starting raw material
42-sulfydryl-4-enanthol is obtained after reduction.The first step reaction is that butyraldehyde and allylmgcl obtain 1-heptene-4-alcohol by grignard reaction, productive rate 87%; Second step reaction 1-heptene-4-alcohol with metachloroperbenzoic acid oxidation, obtains 1,2-epoxy-4-enanthol, productive rate 92% in methylene dichloride; Three-step reaction 1,2-epoxy-4-enanthol reacts with thiocarbamide under the effect of tetraisopropoxy titanium, obtains 1,2-epithio-4-enanthol, productive rate 80%; Four-step reaction 1,2-epithio-4-enanthol in tetrahydrofuran (THF) through LiAlH
42-sulfydryl-4-enanthol is obtained, productive rate 84% after reduction.There is in preparation method of the present invention the advantage that raw material is easy to get, easy and simple to handle and each step reaction yield is high.Reaction formula is as follows:
The present invention relates to the preparation method of structural formula 2-sulfydryl-4-enanthol as follows:
Its main process is: chlorallylene and MAGNESIUM METAL react obtained Grignard reagent allylmgcl, then in diethyl ether solution, obtain 1-heptene-4-alcohol, productive rate 87% with butyraldehyde by grignard reaction; 1-heptene-4-alcohol with metachloroperbenzoic acid oxidation, obtains 1,2-epoxy-4-enanthol, productive rate 92% in methylene dichloride; 1,2-epoxy-4-enanthol reacts with thiocarbamide in tetrahydrofuran solvent under the effect of tetraisopropoxy titanium, obtains 1,2-epithio-4-enanthol, productive rate 80%; 1,2-epithio-4-enanthol in tetrahydrofuran (THF) at a reflux temperature through LiAlH
42-sulfydryl-4-enanthol is obtained, productive rate 84% after reduction.
2-sulfydryl-4-the enanthol 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
(1) preparation of 1-heptene-4-alcohol
Under nitrogen protection effect; to in the four-hole boiling flask that reflux condensing tube is housed; add magnesium chips (0.16mol; 3.8g), anhydrous diethyl ether 40mL and a granule iodine, add chlorallylene (1.0mL); with the initiation reaction of hair dryer mild heat; then drip anhydrous diethyl ether (40mL) solution of chlorallylene (0.1mol, 7.7g), control rate of addition and keep backflow.After dropwising, add anhydrous diethyl ether (40mL), continue to stir and reflux 0.5h.Question response liquid drops to room temperature, is added drop-wise in the Grignard reagent prepared by anhydrous diethyl ether (30mL) solution of butyraldehyde (0.1mol, 7.2g), controls rate of addition and keeps slight backflow.After reinforced, continue to stir and reflux 1h, then reactant is cooled to room temperature.With saturated ammonium chloride solution cancellation reaction, separate ether layer, aqueous phase extracted with diethyl ether, merge organic phase, with saturated common salt washing, anhydrous magnesium sulfate drying.Filtration is revolved and is steamed except desolventizing, then underpressure distillation, collects the cut of 24 ~ 26 DEG C/3.03kPa, obtains colourless transparent liquid 1-heptene-4-alcohol 9.9g, productive rate 87%.
1hNMR (CDCl
3) δ 0.93 (t, J=6.9Hz, 3H, Me (7)), 1.44 (m, 4H, H-C (5) and H-C (6)), 1.70 (s, 1H,-OH), 2.15 (m, 1H, H-C (3)), 2.29 (m, 1H, H-C (3)), 3.65 (m, 1H, H-C (4)), 5.14 (m, 2H, H-C (1)), 5.83 (m, 1H, H-C (2)).
13CNMR(CDCl
3)δ13.99(Me)，18.78(C(6))，38.87(C(5))，41.89(C(3))，70.39(C(4))，117.65(C(1))，134.98(C(2))。
The preparation of (2) 1,2-epoxy-4-enanthol
Methylene dichloride (100mL) and 1-heptene-4-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-25 DEG C of 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 65-66 DEG C/3.03kPa cut and obtain 1,2-epoxy-4-enanthol 12.0g, productive rate 92%.
1hNMR (CDCl
3) δ 0.92 (m, 3H, Me (7)), 1.23 ~ 1.64 (m, 5H, H-C (3), H-C (5) and H-C (6)), 1.75 ~ 1.88 (m, 1H, H-C (3)), 2.25 (br, 1H,-OH), 2.49 (dd, J=4.8, 2.7Hz, 0.56H, H-C (1), Major Diastereomer), 2.60 (dd, J=4.8, 2.7Hz, 0.44H, H-C (1), secondary diastereomer), 2.77 (t, J=4.8Hz, 0.56H, H-C (1), Major Diastereomer), 2.82 (t, J=4.8Hz, 0.44H, H-C (1), secondary diastereomer), 3.07 (m, 0.56H, H-C (2), Major Diastereomer), 3.14 (m, 0.44H, H-C (2), secondary diastereomer), 3.75 ~ 3.94 (m, 1H, H-C (4)).
13cNMR (CDCl
3) δ 13.70 (Me), 18.41 (C (6), Major Diastereomer), 18.42 (C (6), secondary diastereomer), 39.19 (C (3), Major Diastereomer), 39.35 (C (3), secondary diastereomer), 39.48 (C (5), secondary diastereomer), 39.52 (C (5), Major Diastereomer), 46.39 (C (2), Major Diastereomer), 46.94 (C (2), secondary diastereomer), 49.98 (C (1), secondary diastereomer), 50.20 (C (1), Major Diastereomer), 68.29 (C (4), secondary diastereomer), 69.37 (C (4), Major Diastereomer).
The preparation of (3) 1,2-epithio-4-enanthol
Under nitrogen protection, in the four-hole boiling flask of 100mL, add 1,2-epoxy-4-enanthol (1.3g, 10mmol), thiocarbamide (0.9g, 12mmol) and anhydrous tetrahydro furan 40mL, dropwise at room temperature adds Ti (O-i-Pr)
4(3.8mL, 12mmol), stirring reaction, thiocarbamide dissolves gradually, and solution becomes clarification, continues reaction 2h.After reaction terminates, add the dilution of 20mL 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 1,2-epithio-4-enanthol 1.17g, productive rate 80%.
1hNMR (CDCl
3) δ 0.93 (m, 3H, Me (7)), 1.28 ~ 1.57 (m, 4.44H, H-C (3), H-C (5) and H-C (6)), 1.69 (m, 0.56H, H-C (3), Major Diastereomer), 1.75 (br, 1H,-OH), 1.91 ~ 2.13 (m, 1H, H-C (3)), 2.17 (d, J=5.7Hz, 0.44H, H-C (1), secondary diastereomer), 2.25 (d, J=6.3Hz, 0.56H, H-C (1), Major Diastereomer), 2.53 (d, J=5.7Hz, 0.44H, H-C (1), secondary diastereomer), 2.59 (d, J=6.3Hz, 0.56H, H-C (1), Major Diastereomer), 2.98 (m, 0.44H, H-C (2), secondary diastereomer), 3.09 (m, 0.56H, H-C (2), Major Diastereomer), 3.73 ~ 3.88 (m, 1H, H-C (4)).
13cNMR (CDCl
3) δ 13.66 (Me, Major Diastereomer), 13.68 (Me, secondary diastereomer), 18.32 (C (6), secondary diastereomer), 18.41 (C (6), Major Diastereomer), 24.91 (C (2), Major Diastereomer), 25.82 (C (2), secondary diastereomer), 31.85 (C (1), Major Diastereomer), 33.07 (C (1), secondary diastereomer), 38.75 (C (5), secondary diastereomer), 39.32 (C (5), Major Diastereomer), 43.45 (C (3), secondary diastereomer), 43.51 (C (3), Major Diastereomer), 70.84 (C (4), secondary diastereomer), 70.92 (C (4), Major Diastereomer).
(4) preparation of 2-sulfydryl-4-enanthol
Under nitrogen protection; to in the 100mL four-hole boiling flask that thermometer, magnetic stir bar and constant pressure funnel are housed; add Lithium Aluminium Hydride 0.4g (10mmol), anhydrous tetrahydro furan 30mL; 10min is stirred in 0 DEG C of low temperature bath; drip 1 at this temperature; the 20mL anhydrous tetrahydrofuran solution of 2-epithio-4-enanthol (1.5g, 10mmol), about 15min dropwises.Then back flow reaction 3h is warming up to.After reaction mixture cooling, in 0 DEG C of downhill reaction solution, drip 15mL water, stir, drip the sodium hydroxide solution 10mL of 35%, stirring reaction 30min.Reaction mixture filters, with tetrahydrofuran (THF) repetitive scrubbing filter cake 5-6 time.Filtrate anhydrous magnesium sulfate drying.Cross after filtering siccative, revolve steaming, column chromatography (silica gel 100-200 order, V (sherwood oil): V (ethyl acetate)=10: 1) obtains product 2-sulfydryl-4-enanthol 1.24g, productive rate 84%.
1hNMR (CDCl
3) δ 0.90 (3H, t, J=6.9Hz, Me (7)), 1.22-1.64 (8H, m, Me (1), H-C (5), H-C (6), with-SH), 1.64-1.85 (2H, m, H-C (3)), 3.09 (0.25H, m, H-C (2), secondary diastereomer), 3.19 (0.75H, m, H-C (2), Major Diastereomer), 3.72 (0.25H, m, H-C (4), secondary diastereomer), 3.86 (0.75H, m, H-C (4), Major Diastereomer).
13cNMR (CDCl
3) δ 13.61 (C (7)), 18.21 (C (6), secondary diastereomer), 18.39 (C (6), Major Diastereomer), 25.18 (C (1), secondary diastereomer), 26.29 (C (1), Major Diastereomer), 32.04 (C (2), Major Diastereomer), 32.27 (C (2), secondary diastereomer), 39.42 (C (5), secondary diastereomer), 39.61 (C (5), Major Diastereomer), 47.50 (C (3), Major Diastereomer), 48.02 (C (3), secondary diastereomer), 68.71 (C (4), Major Diastereomer), 69.44 (C (4), secondary diastereomer).
Claims (1)
1. a preparation method for 2-sulfydryl-4-enanthol, to is characterized in that with butyraldehyde and chlorallylene, for starting raw material, obtaining 1-heptene-4-alcohol by grignard reaction, then obtain 1,2-epoxy-4-enanthol by epoxidation reaction, epoxide and thiocarbamide are obtained by reacting 1,2-epithio-4-enanthol, through LiAlH
4obtain 2-sulfydryl-4-enanthol after reduction, reaction formula is as follows:
。
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