CN1305828C - Method of synthesizing beta-halogen-beta, garma, unsaturated aldehyde - Google Patents
Method of synthesizing beta-halogen-beta, garma, unsaturated aldehyde Download PDFInfo
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- CN1305828C CN1305828C CN 200510050602 CN200510050602A CN1305828C CN 1305828 C CN1305828 C CN 1305828C CN 200510050602 CN200510050602 CN 200510050602 CN 200510050602 A CN200510050602 A CN 200510050602A CN 1305828 C CN1305828 C CN 1305828C
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- 238000000034 method Methods 0.000 title claims abstract description 12
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 title claims abstract 6
- 230000002194 synthesizing effect Effects 0.000 title 1
- 238000006243 chemical reaction Methods 0.000 claims abstract description 24
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 15
- 150000002085 enols Chemical class 0.000 claims abstract description 14
- 150000002367 halogens Chemical class 0.000 claims abstract description 13
- 239000003960 organic solvent Substances 0.000 claims abstract description 4
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 claims description 26
- 239000000243 solution Substances 0.000 claims description 17
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 15
- 229910052794 bromium Inorganic materials 0.000 claims description 13
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 9
- 125000000217 alkyl group Chemical group 0.000 claims description 9
- 238000003756 stirring Methods 0.000 claims description 7
- 125000003342 alkenyl group Chemical group 0.000 claims description 4
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 claims description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 3
- 239000007864 aqueous solution Substances 0.000 claims description 3
- 238000004440 column chromatography Methods 0.000 claims description 3
- 239000012141 concentrate Substances 0.000 claims description 3
- 238000001035 drying Methods 0.000 claims description 3
- 239000003480 eluent Substances 0.000 claims description 3
- 229910052740 iodine Inorganic materials 0.000 claims description 3
- 239000012044 organic layer Substances 0.000 claims description 3
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical class [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 claims description 3
- 238000013019 agitation Methods 0.000 claims description 2
- 239000000126 substance Substances 0.000 claims description 2
- 238000005406 washing Methods 0.000 claims description 2
- 230000035484 reaction time Effects 0.000 abstract description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 abstract description 4
- 230000005012 migration Effects 0.000 abstract description 3
- 238000013508 migration Methods 0.000 abstract description 3
- 239000012046 mixed solvent Substances 0.000 abstract description 3
- 238000010189 synthetic method Methods 0.000 abstract 1
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 44
- 238000005481 NMR spectroscopy Methods 0.000 description 24
- 238000002360 preparation method Methods 0.000 description 16
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 11
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 11
- 150000001299 aldehydes Chemical class 0.000 description 6
- 150000001728 carbonyl compounds Chemical class 0.000 description 5
- 238000003786 synthesis reaction Methods 0.000 description 4
- 101100391174 Dictyostelium discoideum forC gene Proteins 0.000 description 3
- 229930014626 natural product Natural products 0.000 description 3
- -1 thiazolinyl halogen Chemical class 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 125000001475 halogen functional group Chemical group 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- PBCJIPOGFJYBJE-UHFFFAOYSA-N acetonitrile;hydrate Chemical compound O.CC#N PBCJIPOGFJYBJE-UHFFFAOYSA-N 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 239000002131 composite material Substances 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 238000010511 deprotection reaction Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 239000002532 enzyme inhibitor Substances 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 150000002561 ketenes Chemical class 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 239000005648 plant growth regulator Substances 0.000 description 1
- 239000004476 plant protection product Substances 0.000 description 1
- 239000012429 reaction media Substances 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
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- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The present invention relates to beta-halogenated-beta, gamma-unsaturated aldehyde and a synthetic method thereof, which is characterized in that halogen or NBS reacts with 2, 3-combined enol, generating 1, 2-aryl migration to synthesize the beta-halogenated-beta, gamma-unsaturated aldehyde in a mixed solvent comprising water and organic solvents, wherein halogen or NBS reacts with 2, 3-combined enol, generating 1, 2-aryl migration in the mixed solvent comprising water and an organic solvent, and then the beta-halogenated-beta, gamma-unsaturated aldehyde is obtained. The method has the advantages of moderate reaction condition, short reaction time, high yield, etc., and is suitable for various substituted 2, 3-combined enols. Not only the cost can be lowered, but also industrialization is easy to realize.
Description
Technical field
The present invention relates to the method for a kind of synthetic β-halo-beta, gamma-unsaturated aldehyde, promptly by halogen or NBS and 2, the method for the synthetic β-halo of 3-connection enol reaction-beta, gamma-unsaturated aldehyde.
Background technology
Beta, gamma-beta-unsaturated carbonyl compounds is the important structure unit that constitutes many natural products, is present in widely in the natural product, and also be very important synthetic intermediate in the organic synthesis.Interesting is that many compounds that contain beta, gamma-unsaturated carbonyl structural unit also show unusual biological activity, can be respectively as plant-growth regulator, enzyme inhibitors, plant protection product, anti-tumor activity etc.Also show special fragrance.Because beta, gamma-beta-unsaturated carbonyl compounds has unusual physiologically active and the important application in organic synthesis, the synthetic extensive concern that is subjected to chemists of this compounds.But, be easy to isomery and turn to α more stable on the thermodynamics, beta-unsaturated carbonyl compound because beta, gamma-beta-unsaturated carbonyl compounds has the constructional feature of less stable.Therefore few for beta, gamma-beta-unsaturated carbonyl compounds synthetic bibliographical information, rarely have report in the preparation document of especially relevant beta, gamma-unsaturated olefine aldehydr.And often there are shortcomings such as experimental procedure is loaded down with trivial details, productive rate is low, side reaction is many.As document Ma, S.; Shi, Z.; Li, L.J.Org.Chem.1998,63,4522; Luo, F.J.Org.Chem.1998,63,5656; Luo, F.J.Org.Chem.1999,64,1738; Ma, S.; Li, L.; Xie, H.J.Org.Chem.1999,64,5325; Ma, S.; Yu, S.; Yin, S.J.Org.Chem.2003,68, reported the synthetic of beta, gamma-unsaturated ketenes among the 8996-9002.Document Cornforth, J.W.; Ross, F.P.J.Chem.Soc.Chem.Commun., 1970,1395; Zimmerman, H.E.; Boettcher, R.J.; Braig, W.J.Am.Chem.Soc., 1973,95,2155; Lythgoe, B.; Milner, J.R..; Tideswell, J.Tetrahedron Lett., 1975,30,2593; Hiroi, K.; Nakazawa, K.Chem.Lett., 1980,1077; Zimmerman, H.E.; Cassel, J.M.J.Org.Chem.1989,54,3800; Walba, D.M.; Thurmes, W.N.; Haltiwanger, R.C.J.Org.Chem.1988,53,1046; Armesto, D.; Ortiz, M.J.; Ramos, A.; Horspool, W.M.; Mayoral, E.P.J.Org.Chem.1994 has reported the preparation of beta, gamma-unsaturated olefine aldehydr in 59,8115.But in all these bibliographical informations, all by deprotection, hydrolysis or oxidizing reaction, the carbochain of product does not increase.
β-halo-β, contain the C-X key in γ-unsaturated olefine aldehydr molecule, the structure of thiazolinyl halogen can be carried out a series of linked reaction, thereby in molecule, introduce alkyl or aryl, multiple reaction also can take place in aldehyde radical, so β-halo-beta, gamma-unsaturated olefine aldehydr is a kind of very important organic synthesis intermediate, also be widely used in the synthetic of natural product and medicine in organic synthesis.But do not appear in the newspapers so far in the preparation document for β-halo-beta, gamma-unsaturated olefine aldehydr.We by methodological researchdevelopment a kind of reaction conditions gentleness, the reaction times is short, the method for synthetic β-halo-beta, gamma-unsaturated olefine aldehydr that productive rate is high.
Summary of the invention
At the deficiencies in the prior art, purpose of the present invention just provides a kind of by halogen or N-bromo-succinimide (NBS) and 2, and the reaction of 3-connection enol takes place 1, the method for the synthetic β-halo of 2-aryl migration-beta, gamma-unsaturated aldehyde, and reaction formula is as follows:
X＝Br?or?I
R
1=alkyl or alkenyl, R
2=-OCH
3,-OCH
2O-,-Cl ,-Br ,-NO
2And alkyl etc.
The present invention is achieved by the following scheme, and promptly at water-acetonitrile mixed solvent or methylene dichloride, tetracol phenixin is in the single solvents such as acetonitrile, at room temperature, halogen or NBS and 2,3-connection enol generation cationoid reaction, take place 1 again, the migration of 2-aryl promptly obtains β-halo-beta, gamma-unsaturated olefine aldehydr.Temperature of reaction is a room temperature, and the reaction times is 0.5-24 hour, halogen or NBS and 2, and the ratio of 3-connection enol is 2-1.1.The productive rate of the corresponding β-halo-beta, gamma-unsaturated aldehyde of present method gained is 52-93%.
Method steps of the present invention is:
(1) add entry, organic solvent and as shown in the formula 2 shown in (I) in container, 3-joins enol;
(2) with step (1) gained solution stirring, under agitation slowly drip halogen or N-bromo-succinimide (NBS), at room temperature continued then stirring reaction 0.5-24 hour, its chemical equation is:
In the formula:
R
1Be alkyl or alkenyl; R
2For-OCH
3,-OCH
2O-,-Cl ,-Br ,-NO
2Or alkyl; X is Br or I.
(3) after reaction is finished, in step (2) gained reaction solution, add shrend and go out, stirred 5～15 minutes, add saturated sodium thiosulfate and eliminate excessive halogen or N-bromo-succinimide (NBS);
(4), merge organic layer with step (3) gained solution extracted with diethyl ether; With the saturated nacl aqueous solution washing, anhydrous sodium sulfate drying filters, and concentrates, and makes the eluent rapid column chromatography with petrol ether/ethyl acetate, gets desired product.
Described suc as formula 2 shown in (I), 3-joins enol, R
1=alkyl or alkenyl, R
2=-OCH
3,-OCH
2O-,-Cl ,-Br ,-NO
2Or alkyl.
Described halogen or NBS and 2, the molar ratio of 3-connection enol is 2.5: 1～1: 1.
Compared with prior art, the present invention has the following advantages: 1) reaction does not need anhydrous and oxygen-free, uses water-containing solvent to be reaction medium, environmental friendliness; 2) reaction conditions gentleness, at room temperature reaction, the reaction times is short, and the productive rate height is applicable to 2 of multiple replacement, and 3-joins enol; 3) product is single, easily separated purifying; 4) conversion unit is simple, and cost is low, is easy to industrialization; 5) productive rate of the corresponding β-halo-beta, gamma-unsaturated aldehyde of present method gained is 52-93%.
With halogen or NBS and 2,3-connection enol prepared in reaction β-halo-beta, gamma-unsaturated olefine aldehydr does not appear in the newspapers as yet on the document.Owing to be easy to take place multiple linked reaction at transition metal-catalyzed following alkene halogen key, thereby composite structure is more complicated, beta, gamma-ethylenic unsaturation aldehyde compound that substituting group is abundanter.
Embodiment
Following examples help to understand the present invention, but are not limited to content of the present invention.
Embodiment 1
The preparation of 3-bromo-2-butyl-2-phenyl-3-crotonaldehyde.
In 25mL egg type bottle, add 1-phenyl-2-butyl-2, and 3-divinyl-1-alcohol (81.3mg, 0.4mmol), MeCN (2.4mL), water (0.27mL) stirs and slowly drips 1.6mL bromine/acetonitrile solution (0.5M in MeCN down, 0.8mmol), continue stirring at room reaction 0.5 hour.TLC tracks to after reaction finishes, and adds entry (6mL) cancellation in reaction solution, stirs after 10 minutes, drips the excessive bromine of saturated sodium thiosulfate elimination.With 3 * 25mL extracted with diethyl ether, merge organic layer, wash with saturated nacl aqueous solution, anhydrous sodium sulfate drying filters, and concentrates, make the eluent rapid column chromatography with petrol ether/ethyl acetate (100/1), get product 3-bromo-2-butyl-2-phenyl-3-crotonaldehyde (86.4mg), productive rate is 77%.Oil.
1H?NMR(400MHz，CDCl
3)δ9.68(s，1H)，7.33-7.43(m，5H)，6.05(d，J＝2.4Hz，1H)，5.97(d，J＝2.4Hz，1H)，2.20-2.24(m，1H)，2.12-2.16(m，1H)，1.39-1.45(m，2H)，1.18-1.28(m，2H)，0.94(t，J＝7.6Hz，3H)；
13C?NMR(100MHz，CDCl
3)δ196.2，136.9，133.9，128.9，128.2，128.0，121.4，65.7，31.7，26.9，23.1，13.9；IR(KBr)ν(cm
-1)1730，1619；MS(70eV，EI)m/z(％)：283(M
++1(
81Br)，2.69)，281(M
++1(
79Br)，3.81)，105(100)；HRMS?Calcd?forC
14H
18 79BrO(M
++1)：281.0536.Found：281.0549。
Embodiment 2
The preparation of 3-bromo-2-butyl-2-(4 '-aminomethyl phenyl)-3-crotonaldehyde
Operation steps is with embodiment one.1-(4 '-methyl) phenyl-2-butyl-2, and 3-divinyl-1-alcohol (85.7mg, 0.4mmol), 1.6mL bromine/acetonitrile solution (0.5M in MeCN, 0.8mmol), getting product 3-bromo-2-butyl-2-(4 '-aminomethyl phenyl)-3-crotonaldehyde (84.9mg), productive rate is 73%.
Operation steps is with embodiment 1.1-(4 '-methyl) phenyl-2-butyl-2, (64.1mg, 0.3mmol), (65.5mg 0.36mmol), gets product 3-bromo-2-butyl-2-(4 '-aminomethyl phenyl)-3-crotonaldehyde (78.9mg) to NBS to 3-divinyl-1-alcohol, and productive rate is 90%.Oil，
1H?NMR(400MHz，CDCl
3)δ9.65(s，1H)，7.22(s，4H)，6.04(d，J＝2.4Hz，1H)，5.96(d，J＝2.4Hz，1H)，2.35(s，3H)，2.20-2.23(m，1H)，2.09-2.13(m，1H)，1.39-1.45(m，2H)，1.20-1.29(m，2H)，0.95(t，J＝7.2Hz，3H)；
13C?HMR(100MHz，CDCl
3)δ196.1，137.9，134.2，133.8，129.6，128.0，121.2，65.4，31.6，26.9，23.1，21.0，13.9；IR(KBr)ν(cm
-1)1730，1619；MS(70eV，EI)m/z(％)：296(M
++1(
81Br)，1.30)，294(M
++1(
79Br)，1.31)，143(100)；HRMS?Calcd?for?C
15H
20 79BrO(M
++1)：295.0692；Found：295.0677。
Embodiment 3
The preparation of 3-bromo-2-butyl-2-(4 '-p-methoxy-phenyl)-3-crotonaldehyde
Operation steps is with embodiment 1.1-(4 '-methoxyl group) phenyl-2-butyl-2, and 3-divinyl-1-alcohol (86.8mg, 0.37mmol), 1.6mL bromine/acetonitrile solution (0.5M in MeCN, 0.8mmol), getting product 3-bromo-2-butyl-2-(4 '-p-methoxy-phenyl)-3-crotonaldehyde (82.2mg), productive rate is 71%.Oil.
1H?NMR(400MHz，CDCl
3)δ9.55(s，1H)，7.18(d，J＝8.8Hz，2H)，6.86(d，J＝8.8Hz，2H)，5.97(d，J＝2.4Hz，1H)，5.88(d，J＝2.4Hz，1H)，3.75(s，3H)，2.11-2.15(m，1H)，2.01-2.05(m，1H)，1.31-1.38(m，2H)，1.13-1.25(m，2H)，0.88(t，J＝7.2Hz，3H)；
13C?NMR(100MHz，CDCl
3)δ195.8，159.3，134.4，129.4，128.7，121.1，114.3，65.0，55.2，31.6，26.9，23.1，13.9；IR(KBr)ν(cm
-1)1728，1608；MS(70eV，EI)m/z(％)：312(M
+(
81Br)，3.14)，310(M
+(
79Br)，3.18)，160(100)；HRMS?Calcd?for：C
15H
19 79BrO
2Na(M
++Na)：333.0461；Found：333.0480。
Embodiment 4
The preparation of 3-bromo-2-butyl-2-(3 ', 4 '-dioxy methylene radical phenyl)-3-crotonaldehyde
Operation steps is with embodiment 1.1-(3 ', 4 '-OCH
2O) phenyl-2-butyl-2, and 3-divinyl-1-alcohol (96.2mg, 0.4mmol), 1.6mL (0.5M in MeCN 0.8mmol), gets product 3-bromo-2-butyl-2-(3 ' to bromine/acetonitrile solution, 4 '-dioxy methylene radical phenyl)-and 3-crotonaldehyde (98.7mg), productive rate is 78%.Oil.
1H?NMR(400MHz，CDCl
3)δ9.58(s，1H)，6.77-6.82(m，3H)，6.04(d，J＝2.4Hz，1H)，5.97(s，2H)，5.93(d，J＝2.4Hz，1H)，2.12-2.18(m，1H)，2.03-2.07(m，1H)，1.35-1.43(m，2H)，1.17-1.29(m，2H)，0.95(t，J＝7.2Hz，3H)；
13C?NMR(100MHz，CDCl
3)δ195.5，148.3，147.3，134.1，130.5，121.8，121.2，108.44，108.41，101.3，65.2，31.7，26.9，23.0，13.9；IR(KBr)ν(cm
-1)1728，1618；MS(70eV，EI)m/z(％)：326(M
+(
81Br)，35.90)，324(M
+(
79Br)，37.88)，297(95.82)，295(100)；HRMS?Calcd?for?C
15H
18 79BrO
3(M
++1)：325.0434.Found：325.0461。
Embodiment 5
The preparation of 3-bromo-2-allyl group-2-(4 '-p-methoxy-phenyl)-3-crotonaldehyde
Operation steps is with embodiment 1.1-(4 '-methoxyl group) phenyl-2-allyl group-2, and 3-divinyl-1-alcohol (329.4mg, 1.53mmol), 3.84mL bromine/acetonitrile solution (0.5M in MeCN, 1.92mmol), getting product 3-bromo-2-allyl group-2-(4 '-p-methoxy-phenyl)-3-crotonaldehyde (256.3mg), productive rate is 57%.Oil?
1H?NMR(400MHz，CDCl
3)δ9.57(s，1H)，7.15(d，J＝8.8Hz，2H)，6.85(d，J＝8.8Hz，2H)，5.86-5.88(s，2H)，5.60-5.69(m，1H)，5.11(d，J＝17.2Hz，1H)，5.03(d，J＝9.2Hz，1H)，3.73(s，3H)，2.96(dd，J＝7.6Hz，J＝14Hz，1H)，2.79(dd，J＝7.6Hz，J＝14Hz，1H)；
13C?NMR(100MHz，CDCl
3)δ195.8，159.3，133.7，132.7，129.4，128.0，121.5，118.8，114.3，64.8，55.2，36.5；IR(KBr)ν(cm
-1)1727，1608；MS(70eV，EI)m/z(％)：296(M
+(
81Br)，2.63)，294(M
+(
79Br)，2.45)，145(100)；HRMS?Calcd?for?C
14H
16 79BrO
2(M
++1)：295.0328；Found：295.0322。
Embodiment 6
The preparation of 3-bromo-2-allyl group-2-(4 '-aminomethyl phenyl)-3-crotonaldehyde
Operation steps is with embodiment 1.1-(4 '-methyl) phenyl-2-allyl group-2, and 3-divinyl-1-alcohol (78.4mg, 0.4mmol), 0.88mL bromine/acetonitrile solution (0.5M in MeCN, 0.44mmol), getting product 3-bromo-2-allyl group-2-(4 '-aminomethyl phenyl)-3-crotonaldehyde (56.6mg), productive rate is 52%.
Operation steps is with embodiment 1.1-(4 '-methyl) phenyl-2-allyl group-2, (57.6mg, 0.3mmol), (63.1mg 0.36mmol), gets product 3-bromo-2-allyl group-2-(4 '-aminomethyl phenyl)-3-crotonaldehyde (56.8mg) to NBS to 3-divinyl-1-alcohol, and productive rate is 71%.Oil，
1H?NMR(400MHz，CDCl
3)δ9.69(s，1H)，7.22(s，4H)，5.95-5.96(m，2H)，5.69-5.76(m，1H)，5.19(d，J＝17.2Hz，1H)，5.12(d，J＝9.2Hz，1H)，3.06(dd，J＝8.0Hz，J＝14Hz，1H)，2.89(dd，J＝8.0Hz，J＝14Hz，1H)，2.36(s，3H)；
13C?NMR(100MHz，CDCl
3)δ196.0，138.0，133.5，133.2，132.7，129.7，128.1，121.6，118.8，65.1，36.5，21.0；IR(KBr)ν(cm
-1)1728，1641；MS(70eV，EI)m/z(％)：280(M
+(
81Br)，3.67)，278(M
+(
79Br)，3.75)，129(100)；HRMS?Calcd?for?C
14H
16 79BrO(M
++1)：279.0379；Found：279.0351。
Embodiment 7
The preparation of 3-bromo-2-ethyl-2-(4 '-tolyl)-3-crotonaldehyde
Operation steps is with embodiment 1.1-(4 '-methyl) phenyl-2-ethyl-2, and 3-divinyl-1-alcohol (73.5mg, 0.4mmol), 1.6mL bromine/acetonitrile solution (0.5M in MeCN, 0.8mmol), getting product 3-bromo-2-ethyl-2-(4 '-tolyl)-3-crotonaldehyde (74.4mg), productive rate is 71%.Oil.
1H?NMR(400MHz，CDCl
3)δ9.65(s，1H)，7.23(s，4H)，6.03(d，J＝2.4Hz，1H)，5.97(d，J＝2.4Hz，1H)，2.35(s，3H)，2.28-2.33(m，1H)，2.13-2.17(m，1H)，0.94(t，J＝7.2Hz，3H)；
13C?NMR(100MHz，CDCl
3)δ196.0，137.9，133.8，133.7，129.6，128.1，121.5，65.9，24.6，21.0，9.2；IR(KBr)ν(cm
-1)1730，1620；MS(70eV，EI)m/z(％)：268(M
+(
81Br)，2.02)，266(M
+(
79Br)，2.26)，157(100)；HRMS?Calcd?for?C
13H
16 79BrO(M
++1)：267.0379；Found：267.0356。
Embodiment 8
The preparation of 3-bromo-2-ethyl-2-(4 '-methoxyphenyl)-3-crotonaldehyde
Operation steps is with embodiment 1.1-(4 '-methoxyl group) phenyl-2-ethyl-2, and 3-divinyl-1-alcohol (79.5mg, 0.4mmol), 1.0mL bromine/acetonitrile solution (0.5M in MeCN, 0.5mmol), getting product 3-bromo-2-ethyl-2-(4 '-methoxyphenyl)-3-crotonaldehyde (87.8mg), productive rate is 80%.
Operation steps is with embodiment 1.1-(4 '-methoxyl group) phenyl-2-ethyl-2, (82.0mg, 0.4mmol), (74mg 0.42mmol), gets product 3-bromo-2-ethyl-2-(4 '-methoxyphenyl)-3-crotonaldehyde (99.7mg) to NBS to 3-divinyl-1-alcohol, and productive rate is 88%.Oil，
1H?NMR(400MHz，CDCl
3)δ9.53(s，1H)，7.16(d，J＝10.8Hz，2H)，6.87(d，J＝10.8Hz，2H)，5.94(d，J＝2.4Hz，1H)，5.88(d，J＝2.4Hz，1H)，3.73(s，3H)，2.16-2.28(m，1H)，1.96-2.08(m，1H)，0.85(t，J＝7.2Hz，3H)；
13C?NMR(100MHz，CDCl
3)δ195.7，159.2，134.0，129.4，128.5，121.3，114.3，65.5，55.2，24.6，9.2；IR(KBr)ν(cm
-1)1718，1609；MS(70eV，EI)m/z(％)：284(M
+(
81Br)，3.20)，282(M
+(
79Br)，3.20)，174(100)；HRMS?Calcd?for?C
13H
16 79BrO
2(M
++1)：283.0328.Found：283.0352。
Embodiment 9
The preparation of 3-bromo-2-ethyl-2-(3 ', 4 '-dioxy methylene radical phenyl)-3-crotonaldehyde
Operation steps is with embodiment 1.1-(3 ', 4 '-OCH
2O) phenyl-2-ethyl-2, and 3-divinyl-1-alcohol (87.6mg, 0.4mmol), 1.6mL (0.5M in MeCN 0.8mmol), gets product 3-bromo-2-ethyl-2-(3 ' to bromine/acetonitrile solution, 4 '-dioxy methylene radical phenyl)-and 3-crotonaldehyde (76.2mg), productive rate is 64%.
Operation steps is with embodiment 1.1-(3 ', 4 '-OCH
2O) phenyl-2-ethyl-2, and 3-divinyl-1-alcohol (87.6mg, 0.4mmol), (62.4mg 0.36mmol), gets product 3-bromo-2-ethyl-2-(3 ' to N-bromo-succinimide (NBS), 4 '-dioxy methylene radical phenyl)-and 3-crotonaldehyde (76.6mg), productive rate is 84%.Oil，
1H?NMR(400MHz，CDCl
3)δ9.59(s，1H)，6.78-6.84(m，3H)，6.04(d，J＝2.8Hz，1H)，5.98(s，2H)，5.96(d，J＝2.8Hz，1H)，2.23-2.28(m，1H)，2.06-2.12(m，1H)，0.92(t，J＝7.6Hz，3H)；
13C?NMR(100MHz，CDCl
3)δ195.5，148.3，147.4，133.8，130.4，121.9，121.4，108.48，108.46，101.3，65.7，24.8，9.3；IR(KBr)ν(cm
-1)1728，1618；MS(70eV，EI)m/z(％)：298(M
+(
81Br)，10.21)，296(M
+(
79Br)，10.61)，130(100)；HRMS?Calcd?for?C
13H
14 79BrO
3(M
++1)：297.0121.Found：297.0111。
Embodiment 10
The preparation of 3-iodo-2-butyl-2-(3 ', 4 '-dioxy methylene radical phenyl)-3-crotonaldehyde
Operation steps embodiment 1.1-(3 ', 4 '-OCH
2O) phenyl-2-butyl-2, and 3-divinyl-1-alcohol (99.1mg, 0.4mmol), I
2(204.6mg 0.8mmol), gets product 3-iodo-2-butyl-2-(3 ', 4 '-dioxy methylene radical phenyl)-3-crotonaldehyde (119.1mg), and productive rate is 80%.Product is a white solid, and its fusing point is 57-59 ℃ (a sherwood oil recrystallization).
1H?NMR(400MHz，CDCl
3)δ9.62(s，1H)，6.77-6.85(m，3H)，6.50(d，J＝2.4Hz，1H)，6.29(d，J＝2.4Hz，1H)，5.99(s，2H)，2.14(dt，J＝2.8Hz，J＝8.8Hz，1H)，1.96(dt，J＝2.8Hz，J＝8.8Hz，1H)，1.40-1.44(m，2H)，1.18-1.29(m，2H)，0.94(t，J＝7.6Hz，3H)；
13C?NMR(100MHz，CDCl
3)δ194.5，148.3，147.4，131.5，129.2，121.9，114.4，108.5，108.4，101.3，66.0，32.2，27.0，23.1，13.9；IR(KBr)ν(cm
-1)1725，1605；MS(70eV，EI)m/z(％)：372(M
+，19.41)，174(100)；HRMS?Calcd?forC
15H
18IO
3(M
++1)：373.0295；Found：373.0294。
Embodiment 11
The preparation of 3-iodo-2-ethyl-2-(3 ', 4 '-dioxy methylene radical phenyl)-3-crotonaldehyde
Operation steps is with embodiment 1.1-(3 ', 4 '-OCH
2O) phenyl-2-ethyl-2, and 3-divinyl-1-alcohol (88.7mg, 0.4mmol), I
2(203.2mg 0.8mmol), gets product 3-iodo-2-ethyl-2-(3 ', 4 '-dioxy methylene radical phenyl)-3-crotonaldehyde (96.3mg), and productive rate is 69%.Oil，
1HNMR(400MHz，CDCl
3)δ9.62(s，1H)，6.75-6.83(m，3H)，6.49(d，J＝2.4Hz，1H)，6.31(s，J＝2.4Hz，1H)，5.98(s，2H)，2.21-2.27(m，1H)，1.95-2.00(m，1H)，0.91(t，J＝7.2Hz，3H)；
13C?NMR(100MHz，CDCl
3)δ194.5，148.3，147.4，131.5，129.6，122.0，114.0，108.5，108.4，101.4，66.5，25.2，9.3；IR(KBr)ν(cm
-1)1725，1606；MS(70eV，EI)m/z(％)：344(M
+，9.49)，115(100)；HRMS?Calcd?forC
13H
14IO
3(M
++1)：344.9982；Found：344.9970。
Embodiment 12
The preparation of 3-iodo-2-ethyl-2-(4 '-methoxyphenyl)-3-crotonaldehyde
Operation steps is with embodiment 1.1-(4 '-methoxyl group) phenyl-2-ethyl-2, (40.6mg, 0.2mmol), (108.9mg 0.4mmol), gets product 3-iodo-2-ethyl-2-(4 '-methoxyphenyl)-3-crotonaldehyde (54.6mg) to iodine to 3-divinyl-1-alcohol, and productive rate is 83%.Oil，
1H?NMR(400MHz，CDCl
3)δ9.57(s，1H)，7.15(d，J＝8.8Hz，2H)，6.86(d，J＝8.8Hz，2H)，6.42(s，1H)，6.25(s，1H)，3.74(s，3H)，2.11-2.26(m，1H)，1.91-1.96(m，1H)，0.86(t，J＝7.2Hz，3H)；
13C?NMR(100MHz，CDCl
3)δ194.7，159.2，129.5，129.4，114.32，114.28，66.3，55.2，24.9，9.3；IR(KBr)ν(cm
-1)2723，1725，1607，1580，1510，1254；MS(70eV，EI)m/z(％)：330(M
+，9.0)，174(100)。
Embodiment 13
The preparation of 3-bromo-2-ethyl-2-phenyl-3-crotonaldehyde
Operation steps is with embodiment 1.1-phenyl-2-ethyl-2, (69mg, 0.4mmol), (0.5M in MeCN 0.8mmol), gets product 3-bromo-2-ethyl-2-phenyl-3-crotonaldehyde (77.7mg) to 1.6mL bromine/acetonitrile solution to 3-divinyl-1-alcohol, and productive rate is 77%.Oil，
1H?NMR(400MHz，CDCl
3)δ9.67(s，1H)，7.32-7.41(m，5H)，6.04(s，1H)，5.99(s，1H)，2.29-2.34(m，1H)，2.17-2.21(m，1H)，0.93(t，J＝7.2Hz，3H)；
13C?NMR(100MHz，CDCl
3)δ196.2，136.8，133.5，128.9，128.2，128.0，121.6，66.1，24.8，9.2；MS(70eV，EI)m/z(％)：253(M
+(
79Br)，5.72)，143(100)；HRMS?Calcd?for?C
12H
13 79BrO：253.02498；Found：253.02225。
At last, it is also to be noted that what more than enumerate only is specific embodiments of the invention.Obviously, the invention is not restricted to above embodiment, many distortion can also be arranged.
The present invention can summarize with other the specific form without prejudice to spirit of the present invention and principal character.Therefore, no matter from which point, above-mentioned embodiment of the present invention all can only be thought can not limit the present invention to explanation of the present invention, claims have been pointed out scope of the present invention, and scope of the present invention is not pointed out in above-mentioned explanation, therefore, in implication suitable and any change in the scope, all should think to be included in the scope of claims with claims of the present invention.
Claims (2)
1, the method for a kind of synthetic β-halo-beta, gamma-unsaturated aldehyde is characterized in that, comprises the following steps:
(1) add entry, organic solvent and as shown in the formula 2 shown in (I) in container, 3-joins enol;
(2) with step (1) gained solution stirring, under agitation slowly drip halogen or N-bromo-succinimide, at room temperature continued then stirring reaction 0.5-24 hour, its chemical equation is:
In the formula:
R
1Be alkyl or alkenyl; R
2For-OCH
3,-OCH
2O-,-Cl ,-Br ,-NO
2Or alkyl; X is Br or I;
(3) after reaction is finished, in step (2) gained reaction solution, add shrend and go out, stirred 5～15 minutes, add saturated sodium thiosulfate and eliminate excessive halogen or N-bromo-succinimide;
(4), merge organic layer with step (3) gained solution extracted with diethyl ether; With the saturated nacl aqueous solution washing, anhydrous sodium sulfate drying filters, and concentrates, and makes the eluent rapid column chromatography with petrol ether/ethyl acetate, gets desired product.
2, the method for synthetic according to claim 1 β-halo-beta, gamma-unsaturated aldehyde is characterized in that, described halogen or N-bromo-succinimide and 2, and the molar ratio of 3-connection enol is 2.5: 1～1: 1.
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