CN104945303B - The preparation method of 3 alkenyl Benzazole compounds - Google Patents
The preparation method of 3 alkenyl Benzazole compounds Download PDFInfo
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- CN104945303B CN104945303B CN201510330391.8A CN201510330391A CN104945303B CN 104945303 B CN104945303 B CN 104945303B CN 201510330391 A CN201510330391 A CN 201510330391A CN 104945303 B CN104945303 B CN 104945303B
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
- C07D209/18—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
Abstract
The invention provides the preparation method of 3 alkenyl Benzazole compounds shown in a kind of formula (III)：In stainless steel jar mill, add the N substituted indole compounds shown in raw material formula (I) and olefin(e) compound, catalyst acetic acid palladium, oxidant manganese dioxide, grinding aid silica gel, abrasive media stainless steel ball shown in formula (II), seal ball grinder, it is placed in ball mill and is carried out with 100~650r/min rotating speed after 20~75min of ball-milling reaction, reactant mixture obtains 3 alkenyl Benzazole compounds shown in formula (III) through isolating and purifying；The inventive method is first effectively applied to mechanical grinding techniques in oxidation Heck coupling reactions to prepare 3 alkenyl Benzazole compounds, wide application range of substrates, and economical and efficient, environment-friendly；
Description
(1) technical field
The present invention relates to a kind of preparation method of 3- alkenyls Benzazole compounds, and in particular to machine under a kind of condition of no solvent
The method that tool ball milling prepares 3- alkenyl Benzazole compounds.
(2) technical background
Indoles and its derivative, as the important heterocyclic compound of a class, are the alkaloid parent nucleus for finding most species so far
One of, account for a quarter of known alkaloid.Indole alkaloid structure is typically complex, and has important biology mostly
Activity.Especially 2- replace or 3- substituent indole compounds be widely used in anti-inflammatory (Indomethacin), antiemetic (Ondansetron),
It is depressured (reserpine), antidepression (the bromo- N of 5,6- bis-, N-Dimethyltryptamine indole alkaloid), antitumor (vincaleukoblastinum and vincristine)
Deng field.However, most of Benzazole compounds content in natural resources is extremely low, as it is further carry out pharmaceutical research and
The biggest obstacle of screening active ingredients, therefore indole derivatives is obtained increasingly by academia and life by the method for chemical synthesis
Produce the attention of industrial quarters.
Existing a variety of methods are reported for building 2- substitutions or 3- substituted indole analog derivatives at present, mainly there is following several
Class：
(a) Fischer indole synthesis, with fatty aldehyde, ketone and phenylhydrazine derivant are that raw material is condensed into therewith, then
Cyclization is reset under acid catalysis benzazolyl compounds, such as document are made：(1)J.Heterocycl.Chem.2014,51,854；(2)WO
201004580；(3)CN 102964287；(4) Tetrahedron 2004,60,11719 etc..
(b) Hemetsberger indole synthesis, triazoacetic acid ester and the benzaldehyde of substitution carry out Kenoevenagel contractings
Close and carry out heating cyclization synthesis of indole class compound, such as document again after reaction：(1)Rsc.Adv.2013,3,13232；(2)
Bioorg.Med.Chem.Lett.2013,23,1740；(3) Org.Lett.2011,13,2012 etc..
(c) wittig is into alkene reaction, using indolal and phosphorus ylide reaction synthesis alkene, such as document：(1)
Bioorg.Med.Chem.Lett.2014,24,3385；(2)US 8906952；(3) CN 104125956 etc..
(d) coupling reaction under Pd (II) catalysis, such as document：(1)Tetrahedron 2011,67,5304；(2)US
7446118 etc..
(e) dehydrogenation Heck coupling reactions, such as document：(1)Adv.Synth.Catal.2014,356,1509；(2)
Adv.Synth.Catal.2013,355,1512；(3) Org.Lett.2012,14,5920 etc..
Above-mentioned (a), though the prior synthesizing method such as (b) is more ripe, can realize the extensive of part benzazolyl compounds
Production；But many deficiencies are still suffered from, such as reaction condition is more harsh, and step is tediously long, it is more difficult to obtain the indoles of multifunctional dough
Derivative.(c), (d) synthetic method, using indoles as reaction substrate, further function dough obtains target compound, has simplified many
Substituted indole derivative synthetic reaction route.But pre- function dough substrate is needed to use, Atom economy is low.(e) synthetic method
It is more direct, simply.But still suffer from some shortcomings in reaction, such as using a large amount of environment are unfriendly, intractable organic solvent and
The strong additive of corrosivity, tediously long reaction time so that the application of such reaction is subject to certain restrictions.
The shortcomings of solvent-free reaction is avoided by the danger brought using solvent, toxic and cost increase,
As one of Recent study focus.Mechanical ball mill, as a kind of novel reaction mode for promoting solvent-free reaction, can make anti-
Answer thing more fully, promptly mix, farthest increase the contact surface of reactant, by micro- surface temperature in course of reaction and
The change of pressure improves reactivity, accelerates reaction rate.It has been increasingly becoming a kind of effective means application of organic synthesis
In various organic reactions, such as Aldol condensation reactions, Knoevenagel condensation reactions, Baylis-Hillman reactions,
Michael reacts, wittig reactions etc..Application of the mechanical ball mill technology in dehydrogenation coupling reaction is less, yet there are no and adopts
Carry out aoxidizing the report of Heck coupling reactions with mechanical ball mill mode.
Therefore, oxidation Heck coupling reactions are carried out under the conditions of mechanical ball mill is for preparing 3- alkenyl Benzazole compounds
Important breakthrough to conventional synthesis 3- substituted indole analog derivative methods, can effectively get rid of the use of organic solvent, have
Atom economy is high, and reaction condition is gentle, and regioselectivity is good, the advantage such as yield height.
(3) content of the invention
It is an object of the invention to provide a kind of easy to operate, reaction time is short, mechanical ball mill efficiently prepares 3- alkenyl indoles
The method of class compound.
To achieve the above object, the present invention is adopted the following technical scheme that：
A kind of preparation method of 3- alkenyl Benzazole compounds shown in formula (III), described preparation method is：
In stainless steel jar mill, the N- substituted indole compounds shown in raw material formula (I) and the alkene shown in formula (II) are added
Hydrocarbon compound, catalyst acetic acid palladium, oxidant manganese dioxide, grinding aid silica gel, abrasive media stainless steel ball, seal ball grinder,
It is placed in ball mill and is carried out with 100~650r/min rotating speed after 20~75min of ball-milling reaction, reactant mixture is pure through separating
Change, obtain the 3- alkenyl Benzazole compounds shown in formula (III)；
The amount of N- substituted indole compounds and the material that feeds intake of the olefin(e) compound shown in formula (II) shown in the formula (I)
The ratio between be 1：0.5~5.0；The amount of the catalyst acetic acid palladium and the material that feeds intake of the N- substituted indole compounds shown in formula (I)
The ratio between be 0.01~0.4：1；The oxidant manganese dioxide and the material that feeds intake of the N- substituted indole compounds shown in formula (I)
The ratio between amount is 0.5~4.0：1；
In formula (I) or formula (III), R1For hydrogen, methyl, ethyl or benzyl；R2For methyl, methoxyl group, chlorine, bromine or nitro；
In formula (II) or formula (III), R3For methoxycarbonyl group, carbethoxyl group or butoxy carbonyl.
Preparation method of the present invention, it is the N- substitutions shown in formula (I) to recommend the quality consumption of the grinding aid silica gel
2~8 times of benzazolyl compounds quality, preferably 2~5 times.
A diameter of 8~12mm, the preferably 10mm of the usual abrasive media stainless steel ball, and generally of stainless steel ball
Number is 2.
It is preferred that the material that feeds intake of the N- substituted indole compounds and the olefin(e) compound shown in formula (II) shown in the formula (I)
The ratio between amount be 1：1~3.0.
It is preferred that the ratio between the catalyst acetic acid palladium and amount for the material that feeds intake of N- substituted indole compounds shown in formula (I) are
0.05~0.25：1.
It is preferred that the ratio between amount for the material that feeds intake of N- substituted indole compounds shown in the oxidant manganese dioxide and formula (I)
For 1~3：1.
It is preferred that the rotating speed of the ball mill is 300~600r/min.
It is preferred that the time of the ball-milling reaction is 30~60min.
The method for recommending the reactant mixture to isolate and purify is：Stainless steel ball is taken out from reactant mixture, will be reacted
Mixture carries out column chromatography for separation, with petrol ether/ethyl acetate volume ratio 2~50：1 mixed solvent is eluant, eluent, and collection contains
The eluent of target compound, is evaporated off drying after solvent, produces the 3- alkenyl Benzazole compounds shown in formula (III).
Specifically, recommending the preparation method of the present invention to be：
In stainless steel jar mill, the N- substituted indole compounds shown in raw material formula (I) and the alkene shown in formula (II) are added
Hydrocarbon compound, catalyst acetic acid palladium, oxidant manganese dioxide, grinding aid silica gel, 2 8~12mm of diameter stainless steel ball, sealing
Ball grinder, is placed in ball mill and is carried out with 300~600r/min rotating speed after 30~60min of ball-milling reaction, from reactant mixture
Middle taking-up stainless steel ball, column chromatography for separation is carried out by reactant mixture, with petrol ether/ethyl acetate volume ratio 5~40：1 it is mixed
Bonding solvent is eluant, eluent, collects the eluent containing target compound, is evaporated off drying after solvent, produces the 3- alkene shown in formula (III)
Base Benzazole compounds；
The amount of N- substituted indole compounds and the material that feeds intake of the olefin(e) compound shown in formula (II) shown in the formula (I)
The ratio between be 1：1~3.0；The amount of the material that feeds intake of N- substituted indole compounds shown in the catalyst acetic acid palladium and formula (I) it
Than for 0.05~0.25：1；The oxidant manganese dioxide and the material that feeds intake of the N- substituted indole compounds shown in formula (I)
The ratio between amount is 1~3：1；The quality consumption of the grinding aid silica gel be formula (I) shown in N- substituted indole compound quality 2~
5 times.
Beneficial effects of the present invention are embodied in：
(1) the inventive method is first effectively applied to mechanical grinding techniques in oxidation Heck coupling reactions to prepare 3-
Alkenyl Benzazole compounds；
(2) conventional method reaction typically all carry out in a solvent, the inventive method effectively got rid of reaction in environment not
The use of friendiy solvent；
(3) the inventive method substantially reduces the reaction time；
(4) yield of the inventive method not only product is higher, and regioselectivity preferably, has also widened being applicable for reaction substrate
Scope.
In summary, the inventive method have that the reaction time is short, reaction yield is high, regioselectivity good, it is easy to operate, after
The advantages of processing is simple, pollution is few, is a kind of environmentally friendly chemistry synthetic method with preferable popularizing application prospect.
(4) embodiment
The technical scheme that by the following specific examples further illustrate the invention, but protection scope of the present invention is not
It is only limitted to this.
The preparation of the N- methyl -3- ethoxycarbonyl-ethenyl indoles of embodiment 1
N- methyl indols (131mg, 1mmol), ethyl acrylate (50mg, 0.5mmol), vinegar are added in 12mL ball grinders
Sour palladium (22.4mg, 0.1mmol), manganese dioxide (174mg, 2mmol), silica gel (550mg) adds 2 a diameter of 10mm's
Stainless steel ball, covers ball milling cover, and be put into ball mill makes mixture react 60 minutes with 600r/min rotating speed operation.TLC (takes
Sample is dissolved in ethyl acetate) tracking extent of reaction, after reaction terminates, complete reaction mixture is poured out from grinding pot, taken out
Stainless steel ball, petroleum ether and ethyl acetate (volume ratio 25 are directly used by solid powder:1) eluant, eluent carries out column chromatography for separation,
Eluent of the gained containing target compound is evaporated off drying after solvent, obtains N- methyl -3- ethoxycarbonyl-ethenyl indoles 68.7mg,
Yield is 30%.
White solid, 86-87 DEG C of fusing point,1H NMR(400MHz,CDCl3)δ7.86-7.79(m,2H,including-CH
=CH-Ar, d, J=16.0Hz), 7.29-7.26 (m, 1H), 7.24-7.20 (m, 1H), 7.19-7.16 (m, 1H), 6.34 (d, J
=16.0Hz, 1H), 4.20 (q, J=7.12Hz, 2H), 3.74 (s, 3H), 1.29 (t, J=7.12Hz, 3H)；13C NMR
(100MHz,CDCl3)δ167.6,137.5,132.7,125.5,122.5,120.8,120.2,112.2,111.7,109.6,
60.08,33.39,14.90；MS(ESI):M/z=230.3 ([M+H]+).
The preparation of the N- methyl -3- ethoxycarbonyl-ethenyl indoles of embodiment 2
N- methyl indols (131mg, 1mmol), ethyl acrylate (100mg, 1mmol), vinegar are added in 12mL ball grinders
Sour palladium (11.2mg, 0.05mmol), manganese dioxide (87mg, 1mmol), silica gel (550mg) adds 2 a diameter of 10mm's
Stainless steel ball, covers ball milling cover, and be put into ball mill makes mixture react 45 minutes with 600r/min per minute rotating speed operation.
TLC (sampling is dissolved in ethyl acetate) tracks extent of reaction, after reaction terminates, and complete reaction mixture is fallen from grinding pot
Go out, take out stainless steel ball, solid powder is directly used into petroleum ether and ethyl acetate (volume ratio 20:1) eluant, eluent carries out post layer
Analysis separation, eluent of the gained containing target compound is evaporated off drying after solvent, obtains N- methyl -3- ethoxycarbonyl-ethenyl indoles
103.1mg, yield is 45%.Physical data be the same as Example 1.
The preparation of the N- methyl -3- ethoxycarbonyl-ethenyl indoles of embodiment 3
N- methyl indols (131mg, 1mmol), ethyl acrylate (100mg, 1mmol), vinegar are added in 12mL ball grinders
Sour palladium (11.2mg, 0.05mmol), manganese dioxide (130.5mg, 1.5mmol), silica gel (550mg), add 2 it is a diameter of
10mm stainless steel ball, covers ball milling cover, and be put into ball mill reacts mixture with 600r/min per minute rotating speed operation
45 minutes.TLC (sampling is dissolved in ethyl acetate) tracks extent of reaction, after reaction terminates, by complete reaction mixture from grinding
Poured out in tank, take out stainless steel ball, solid powder is directly used into petroleum ether and ethyl acetate (volume ratio 20:1) eluant, eluent enters
Row column chromatography for separation, eluent of the gained containing target compound is evaporated off drying after solvent, obtains N- methyl -3- carbethoxyl group ethene
Base indoles 137.4mg, yield is 60%.Physical data be the same as Example 1.
The preparation of the N- methyl -3- ethoxycarbonyl-ethenyl indoles of embodiment 4
N- methyl indols (131mg, 1mmol), ethyl acrylate (100mg, 1mmol), vinegar are added in 12mL ball grinders
Sour palladium (11.2mg, 0.05mmol), manganese dioxide (217.5mg, 2.5mmol), silica gel (550mg), add 2 it is a diameter of
10mm stainless steel ball, covers ball milling cover, and be put into ball mill reacts mixture with 600r/min per minute rotating speed operation
45 minutes.TLC (sampling is dissolved in ethyl acetate) tracks extent of reaction, after reaction terminates, by complete reaction mixture from grinding
Poured out in tank, take out stainless steel ball, solid powder is directly used into petroleum ether and ethyl acetate (volume ratio 20:1) eluant, eluent enters
Row column chromatography for separation, eluent of the gained containing target compound is evaporated off drying after solvent, obtains N- methyl -3- carbethoxyl group ethene
Base indoles 155.7mg, yield is 68%.Physical data be the same as Example 1.
The preparation of embodiment 5N- methyl -3- ethoxycarbonyl-ethenyl indoles
The addition N- methyl indols (131mg, 1mmol) in 12mL ball grinders, ethyl acrylate (150mg, 1.5mmol),
Palladium (26.9mg, 0.12mmol), manganese dioxide (261mg, 3mmol), silica gel (550mg) adds 2 a diameter of 10mm
Stainless steel ball, cover ball milling cover, be put into ball mill makes mixture react 45 points with the operation of 600r/min per minute rotating speed
Clock.TLC (sampling is dissolved in ethyl acetate) tracks extent of reaction, after reaction terminates, by complete reaction mixture from grinding pot
Pour out, take out stainless steel ball, solid powder is directly used into petroleum ether and ethyl acetate (volume ratio 20:1) eluant, eluent carries out post
Chromatography, eluent of the gained containing target compound is evaporated off drying after solvent, obtains N- methyl -3- ethoxycarbonyl-ethenyls Yin
Diindyl 160.3mg, yield is 70%.Physical data be the same as Example 1.
The preparation of embodiment 6N- methyl -3- ethoxycarbonyl-ethenyl indoles
N- methyl indols (131mg, 1mmol), ethyl acrylate (200mg, 2mmol), vinegar are added in 12mL ball grinders
Sour palladium (44.8mg, 0.2mmol), manganese dioxide (174mg, 2mmol), silica gel (550mg) adds 2 a diameter of 10mm's
Stainless steel ball, covers ball milling cover, and be put into ball mill makes mixture react 45 minutes with 600r/min per minute rotating speed operation.
TLC (sampling is dissolved in ethyl acetate) tracks extent of reaction, after reaction terminates, and complete reaction mixture is fallen from grinding pot
Go out, take out stainless steel ball, solid powder is directly used into petroleum ether and ethyl acetate (volume ratio 15:1) eluant, eluent carries out post layer
Analysis separation, eluent of the gained containing target compound is evaporated off drying after solvent, obtains N- methyl -3- ethoxycarbonyl-ethenyl indoles
194.6mg, yield is 85%.Physical data be the same as Example 1.
The preparation of the N- methyl -3- ethoxycarbonyl-ethenyl indoles of embodiment 7
N- methyl indols (131mg, 1mmol), ethyl acrylate (200mg, 2mmol), vinegar are added in 12mL ball grinders
Sour palladium (44.8mg, 0.2mmol), manganese dioxide (174mg, 2mmol), silica gel (550mg) adds 2 a diameter of 10mm's
Stainless steel ball, covers ball milling cover, and be put into ball mill makes mixture react 45 minutes with 500r/min per minute rotating speed operation.
TLC (sampling is dissolved in ethyl acetate) tracks extent of reaction, after reaction terminates, and complete reaction mixture is fallen from grinding pot
Go out, take out stainless steel ball, solid powder is directly used into petroleum ether and ethyl acetate (volume ratio 10:1) eluant, eluent carries out post layer
Analysis separation, eluent of the gained containing target compound is evaporated off drying after solvent, obtains N- methyl -3- ethoxycarbonyl-ethenyl indoles
178.6mg, yield is 78%.Physical data be the same as Example 1.
The preparation of the N- methyl -3- ethoxycarbonyl-ethenyl indoles of embodiment 8
N- methyl indols (131mg, 1mmol), ethyl acrylate (500mg, 5mmol), vinegar are added in 12mL ball grinders
Sour palladium (22.4mg, 0.1mmol), manganese dioxide (174mg, 2mmol), silica gel (550mg) adds 2 a diameter of 10mm's
Stainless steel ball, covers ball milling cover, and be put into ball mill makes mixture react 45 minutes with 600r/min per minute rotating speed operation.
TLC (sampling is dissolved in ethyl acetate) tracks extent of reaction, after reaction terminates, and complete reaction mixture is fallen from grinding pot
Go out, take out stainless steel ball, solid powder is directly used into petroleum ether and ethyl acetate (volume ratio 5:1) eluant, eluent carries out column chromatography
Separation, eluent of the gained containing target compound is evaporated off drying after solvent, obtains N- methyl -3- ethoxycarbonyl-ethenyl indoles
148.9mg, yield is 65%.Physical data be the same as Example 1.
The preparation of the N- methyl -3- ethoxycarbonyl-ethenyl indoles of embodiment 9
N- methyl indols (131mg, 1mmol), ethyl acrylate (100mg, 1mmol), vinegar are added in 12mL ball grinders
Sour palladium (56mg, 0.25mmol), manganese dioxide (174mg, 2mmol), silica gel (550mg) adds 2 a diameter of 10mm not
Become rusty steel ball, covers ball milling cover, and be put into ball mill makes mixture react 45 minutes with 600r/min per minute rotating speed operation.
TLC (sampling is dissolved in ethyl acetate) tracks extent of reaction, after reaction terminates, and complete reaction mixture is fallen from grinding pot
Go out, take out stainless steel ball, solid powder is directly used into petroleum ether and ethyl acetate (volume ratio 40:1) eluant, eluent carries out post layer
Analysis separation, eluent of the gained containing target compound is evaporated off drying after solvent, obtains N- methyl -3- ethoxycarbonyl-ethenyl indoles
201.5mg, yield is 88%.Physical data be the same as Example 1.
It is prepared by the N- methyl -3- ethoxycarbonyl-ethenyls indoles of embodiment 10
N- methyl indols (131mg, 1mmol), ethyl acrylate (100mg, 1mmol), vinegar are added in 12mL ball grinders
Sour palladium (22.4mg, 0.1mmol), manganese dioxide (174mg, 2mmol), silica gel (260mg) adds 2 a diameter of 10mm's
Stainless steel ball, covers ball milling cover, and be put into ball mill makes mixture react 50 minutes with 600r/min per minute rotating speed operation.
TLC (sampling is dissolved in ethyl acetate) tracks extent of reaction, after reaction terminates, and complete reaction mixture is fallen from grinding pot
Go out, take out stainless steel ball, solid powder is directly used into petroleum ether and ethyl acetate (volume ratio 40:1) eluant, eluent carries out post layer
Analysis separation, eluent of the gained containing target compound is evaporated off drying after solvent, obtains N- methyl -3- ethoxycarbonyl-ethenyl indoles
80.2mg, yield is 35%.Physical data be the same as Example 1.
The preparation of the N- methyl -3- ethoxycarbonyl-ethenyl indoles of embodiment 11
N- methyl indols (131mg, 1mmol), ethyl acrylate (100mg, 1mmol), vinegar are added in 12mL ball grinders
Sour palladium (22.4mg, 0.1mmol), manganese dioxide (174mg, 2mmol), silica gel (460mg) adds 2 a diameter of 10mm's
Stainless steel ball, covers ball milling lid, and be put into ball mill makes mixture react 60 minutes with 600r/min per minute rotating speed operation.
TLC (sampling is dissolved in ethyl acetate) tracks extent of reaction, after reaction terminates, and complete reaction mixture is fallen from grinding pot
Go out, take out stainless steel ball, solid powder is directly used into petroleum ether and ethyl acetate (volume ratio 20:1) eluant, eluent carries out post layer
Analysis separation, eluent of the gained containing target compound is evaporated off drying after solvent, obtains N- methyl -3- ethoxycarbonyl-ethenyl indoles
171.8mg, yield is 75%.Physical data be the same as Example 1.
The preparation of the N- methyl -3- ethoxycarbonyl-ethenyl indoles of embodiment 12
N- methyl indols (131mg, 1mmol), ethyl acrylate (100mg, 1mmol), vinegar are added in 12mL ball grinders
Sour palladium (22.4mg, 0.1mmol), manganese dioxide (174mg, 2mmol), silica gel (650mg) adds 2 a diameter of 10mm's
Stainless steel ball, covers ball milling cover, and be put into ball mill makes mixture react 60 minutes with 600r/min per minute rotating speed operation.
TLC (sampling is dissolved in ethyl acetate) tracks extent of reaction, after reaction terminates, and complete reaction mixture is fallen from grinding pot
Go out, take out stainless steel ball, solid powder is directly used into petroleum ether and ethyl acetate (volume ratio 20:1) eluant, eluent carries out post layer
Analysis separation, eluent of the gained containing target compound is evaporated off drying after solvent, obtains N- methyl -3- ethoxycarbonyl-ethenyl indoles
160.3mg, yield is 70%.Physical data be the same as Example 1
The preparation of the N- methyl -3- ethoxycarbonyl-ethenyl indoles of embodiment 13
N- methyl indols (131mg, 1mmol), ethyl acrylate (100mg, 1mmol), vinegar are added in 12mL ball grinders
Sour palladium (22.4mg, 0.1mmol), manganese dioxide (174mg, 2mmol), silica gel (400mg) adds 2 a diameter of 10mm's
Stainless steel ball, covers ball milling cover, and be put into ball mill makes mixture react 60 minutes with 450r/min per minute rotating speed operation.
TLC (sampling is dissolved in ethyl acetate) tracks extent of reaction, after reaction terminates, and complete reaction mixture is fallen from grinding pot
Go out, take out stainless steel ball, solid powder is directly used into petroleum ether and ethyl acetate (volume ratio 20:1) eluant, eluent carries out post layer
Analysis separation, eluent of the gained containing target compound is evaporated off drying after solvent, obtains N- methyl -3- ethoxycarbonyl-ethenyl indoles
137.4mg, yield is 60%.Physical data be the same as Example 1.
The preparation of the N- methyl -3- ethoxycarbonyl-ethenyl indoles of embodiment 14
N- methyl indols (131mg, 1mmol), ethyl acrylate (100mg, 1mmol), vinegar are added in 12mL ball grinders
Sour palladium (22.4mg, 0.1mmol), manganese dioxide (174mg, 2mmol), silica gel (400mg) adds 2 a diameter of 10mm's
Stainless steel ball, covers ball milling cover, and be put into ball mill makes mixture react 60 minutes with 300r/min per minute rotating speed operation.
TLC (sampling is dissolved in ethyl acetate) tracks extent of reaction, after reaction terminates, and complete reaction mixture is fallen from grinding pot
Go out, take out stainless steel ball, solid powder is directly used into petroleum ether and ethyl acetate (volume ratio 20:1) eluant, eluent carries out post layer
Analysis separation, eluent of the gained containing target compound is evaporated off drying after solvent, obtains N- methyl -3- ethoxycarbonyl-ethenyl indoles
103.1mg, yield is 45%.Physical data be the same as Example 1.
The preparation of the N- methyl -3- ethoxycarbonyl-ethenyl indoles of embodiment 15
N- methyl indols (131mg, 1mmol), ethyl acrylate (100mg, 1mmol), vinegar are added in 12mL ball grinders
Sour palladium (22.4mg, 0.1mmol), manganese dioxide (174mg, 2mmol), silica gel (525mg) adds 2 a diameter of 10mm's
Stainless steel ball, covers ball milling cover, and be put into ball mill makes mixture react 30 minutes with 600r/min per minute rotating speed operation.
TLC (sampling is dissolved in ethyl acetate) tracks extent of reaction, after reaction terminates, and complete reaction mixture is fallen from grinding pot
Go out, take out stainless steel ball, solid powder is directly used into petroleum ether and ethyl acetate (volume ratio 20:1) eluant, eluent carries out post layer
Analysis separation, eluent of the gained containing target compound is evaporated off drying after solvent, obtains N- methyl -3- ethoxycarbonyl-ethenyl indoles
167.2mg, yield is 73%.Physical data be the same as Example 1.
The preparation of the positive butoxy carbonyl vinyl indoles of N- methyl -3- of embodiment 16
The addition N- methyl indols (131mg, 1mmol) in 12mL ball grinders, butyl acrylate (166mg, 1.3mmol),
Palladium (22.4mg, 0.1mmol), manganese dioxide (174mg, 2mmol), silica gel (525mg) adds 2 a diameter of 10mm
Stainless steel ball, cover ball milling cover, be put into ball mill makes mixture react 40 points with the operation of 600r/min per minute rotating speed
Clock.TLC (sampling is dissolved in ethyl acetate) tracks extent of reaction, after reaction terminates, by complete reaction mixture from grinding pot
Pour out, take out stainless steel ball, solid powder is directly used into petroleum ether and ethyl acetate (volume ratio 20:1) eluant, eluent carries out post
Chromatography, eluent of the gained containing target compound is evaporated off drying after solvent, obtains the positive butoxy carbonyl vinyl of N- methyl -3-
Indoles 185.0mg, yield is 72%.
White solid, 70-71 DEG C of fusing point,1H NMR(400MHz,CDCl3)δ7.92-7.84(m,2H,including-CH
=CH-Ar, d, J=16.0Hz), 7.35-7.31 (m, 2H), 7.30-7.21 (m, 2H), 6.39 (d, J=16.0Hz, 1H),
4.20 (t, J=6.6Hz, 2H), 3.81 (s, 3H), 1.74-1.65 (m, 2H), 1.51-1.40 (m, 2H), 0.97 (t, J=
7.4Hz,3H)；13C NMR(100MHz,CDCl3)δ168.2,137.9,137.7,132.8,122.8,121.1,120.5,
112.7,112.1,109.8,64.0,33.2,31.1,19.4,13.9；MS(ESI):257.9([M+H]+).
The preparation of the N- benzyl -3- ethoxycarbonyl-ethenyl indoles of embodiment 17
The addition N- benzylindoles (207mg, 1mmol) in 12mL ball grinders, ethyl acrylate (130mg, 1.3mmol),
Palladium (22.4mg, 0.1mmol), manganese dioxide (174mg, 2mmol), silica gel (525mg) adds 2 a diameter of 10mm
Stainless steel ball, cover ball milling cover, be put into ball mill makes mixture react 40 points with the operation of 600r/min per minute rotating speed
Clock.TLC (sampling is dissolved in ethyl acetate) tracks extent of reaction, after reaction terminates, by complete reaction mixture from grinding pot
Pour out, take out stainless steel ball, solid powder is directly used into petroleum ether and ethyl acetate (volume ratio 20:1) eluant, eluent carries out post
Chromatography, eluent of the gained containing target compound is evaporated off drying after solvent, obtains N- benzyl -3- ethoxycarbonyl-ethenyls Yin
Diindyl 198.3mg, yield is 65%.
Light green solid, 104-105 DEG C of fusing point,1H NMR(400MHz,CDCl3)δ7.95-7.91(m,1H),7.88(d,J
=16.0Hz, 1H), 7.39 (s, 1H), 7.35-7.27 (m, 4H), 7.27-7.22 (m, 3H, including CDCl3),7.16-
7.10 (m, 2H), 6.42 (d, J=16.0Hz, 1H), 5.31 (s, 2H), 4.26 (q, J=7.1Hz, 2H), 1.35 (t, J=
7.1Hz,3H).13C NMR(100MHz,CDCl3)δ167.9,137.6,137.5,136.0,132.1,128.8(2C),127.9,
126.8(2C),126.2,122.9,121.3,120.5,113.1,112.6,110.3,60.0,50.4,14.6；MS(ESI):
306([M+H]+).
The preparation of the N- methyl -3- ethoxycarbonyl-ethenyl -5- chloro-indoles of embodiment 18
The addition N- methyl-5-chloros indoles (165mg, 1mmol) in 12mL ball grinders, ethyl acrylate (130mg,
1.3mmol), palladium (22.4mg, 0.1mmol), manganese dioxide (174mg, 2mmol), silica gel (525mg) adds 2 directly
Footpath is 10mm stainless steel ball, covers ball milling cover, and be put into ball mill makes mixture with 600r/min per minute rotating speed operation
Reaction 40 minutes.TLC (sampling is dissolved in ethyl acetate) track extent of reaction, reaction terminate after, by complete reaction mixture from
Poured out in grinding pot, take out stainless steel ball, solid powder is directly used into petroleum ether and ethyl acetate (volume ratio 20:1) elution
Agent carries out column chromatography for separation, and eluent of the gained containing target compound is evaporated off drying after solvent, obtains N- methyl -3- carbethoxyl groups
Vinyl -5- chloro-indole 184.1mg, yield is 70%.
White solid, 114-116 DEG C of fusing point,1H NMR(400MHz,CDCl3) δ 7.85 (s, 1H), 7.80 (d, J=
16.0Hz, 1H), 7.32 (s, 1H), 7.26-7.21 (m, 2H), 6.33 (d, J=16.0Hz, 1H), 4.26 (q, J=7.1Hz,
2H), 3.79 (s, 3H), 1.35 (t, J=7.1Hz, 3H)；13C NMR(100MHz,CDCl3)δ167.7,137.0,136.1,
133.7,126.9,126.6,122.9,119.8,112.8,111.3,110.8,60.1,33.3,14.5；MS(ESI):264([M
+H]+).
The preparation of the N- methyl -3- ethoxycarbonyl-ethenyl -5- bromo indoles of embodiment 19
The addition N- methyl -5- bromo indoles (209mg, 1mmol) in 12mL ball grinders, ethyl acrylate (130mg,
1.3mmol), palladium (22.4mg, 0.1mmol), manganese dioxide (174mg, 2mmol), silica gel (525mg) adds 2 directly
Footpath is 10mm stainless steel ball, covers ball milling lid, and be put into ball mill makes mixture anti-with 600r/min per minute rotating speed operation
Answer 40 minutes.TLC (sampling is dissolved in ethyl acetate) tracks extent of reaction, after reaction terminates, by complete reaction mixture from grinding
Poured out in grinding jar, take out stainless steel ball, solid powder is directly used into petroleum ether and ethyl acetate (volume ratio 20:1) eluant, eluent
Column chromatography for separation is carried out, eluent of the gained containing target compound is evaporated off drying after solvent, obtains N- methyl -3- carbethoxyl group second
Alkenyl -5- bromo indole 214.9mg, yield is 70%.
Light yellow solid, 116-118 DEG C of fusing point,1H NMR(400MHz,CDCl3) δ 8.01 (d, J=1.2Hz, 1H), 7.80
(d, J=16.0Hz, 1H), 7.37 (dd, J=2.0,1.6Hz, 1H), 7.31 (s, 1H), 7.21-7.17 (m, 1H), 6.34 (d, J
=16.0Hz, 1H), 4.28 (q, 7.1Hz, 2H), 3.79 (s, 3H), 1.37 (t, J=7.1Hz, 3H)；13C NMR(100MHz,
CDCl3)δ167.3,136.7,136.1,133.3,127.0,125.3,122.7,114.4,112.8,111.2,111.1,
60.3,33.6,14.9；MS(ESI):309([M+H]+).
The preparation of the N- benzyl -3- ethoxycarbonyl-ethenyl -5- bromo indoles of embodiment 20
The addition N- benzyl -5- bromo indoles (286mg, 1mmol) in 12mL ball grinders, ethyl acrylate (130mg,
1.3mmol), palladium (22.4mg, 0.1mmol), manganese dioxide (174mg, 2mmol), silica gel (525mg) adds 2 directly
Footpath is 10mm stainless steel ball, covers ball milling lid, and be put into ball mill makes mixture anti-with 600r/min per minute rotating speed operation
Answer 40 minutes.TLC (sampling is dissolved in ethyl acetate) tracks extent of reaction, after reaction terminates, by complete reaction mixture from grinding
Poured out in grinding jar, take out stainless steel ball, solid powder is directly used into petroleum ether and ethyl acetate (volume ratio 20:1) eluant, eluent
Column chromatography for separation is carried out, eluent of the gained containing target compound is evaporated off drying after solvent, obtains N- benzyl -3- carbethoxyl group second
Alkenyl -5- bromo indole 260.5mg, yield is 68%.
White solid, 74-76 DEG C of fusing point,1H NMR(400MHz,CDCl3) δ 8.03 (d, J=2.0Hz, 1H), 7.80 (d, J
=16.0Hz, 1H), 7.37 (s, 1H), 7.34-7.26 (m, 4H), 7.14 (d, J=8.8Hz, 1H), 7.11-7.07 (m, 2H),
6.35 (d, J=16.0Hz, 1H), 5.28 (s, 2H), 4.26 (q, J=7.1Hz, 2H), 1.35 (t, J=7.1Hz, 3H)；13C
NMR(100MHz,CD3Cl)δ167.7,136.9,136.0,135.5,132.9,128.9(2C),128.1,127.7,126.7
(2C),125.9,123.2,114.8,113.6,112.0,111.8,60.2,50.7,14.6.MS(ESI):384([M+H]+).
The preparation of the 2- methyl -3- ethoxycarbonyl-ethenyl indoles of embodiment 21
The addition 2 methyl indole (117mg, 1mmol) in 12mL ball grinders, ethyl acrylate (130mg, 1.3mmol),
Palladium (22.4mg, 0.1mmol), manganese dioxide (174mg, 2mmol), silica gel (500mg) adds 2 a diameter of 10mm
Stainless steel ball, cover ball milling cover, be put into ball mill makes mixture react 40 points with the operation of 600r/min per minute rotating speed
Clock.TLC (sampling is dissolved in ethyl acetate) tracks extent of reaction, after reaction terminates, by complete reaction mixture from grinding pot
Pour out, take out stainless steel ball, solid powder is directly used into petroleum ether and ethyl acetate (volume ratio 20:1) eluant, eluent carries out post
Chromatography, eluent of the gained containing target compound is evaporated off drying after solvent, obtains 2- methyl -3- ethoxycarbonyl-ethenyls Yin
Diindyl 53.75mg, yield is 25%.
Light yellow solid, 177-178 DEG C of fusing point,1H NMR(400MHz,CDCl3) δ 8.21 (s, 1H), 7.92 (d, J=
16.0Hz, 1H), 7.88-7.82 (m, 1H), 7.33-7.26 (m, 1H), 7.22-7.15 (m, 1H), 6.41 (d, J=16.0Hz,
1H), 4.27 (q, J=7.1Hz, 2H), 2.56 (s, 3H), 1.35 (t, J=7.1Hz, 3H)；13C NMR(100MHz,CDCl3)δ
168.6,139.9,137.4,135.6,126.3,122.3,121.2,119.8,111.9,110.8,109.5,60.1,14.6,
12.4.MS(ESI):230([M+H]+).
The preparation of the 3- ethoxycarbonyl-ethenyl -5- methoxy-Indoles of embodiment 22
The addition 5- methoxy-Indoles (147mg, 1mmol) in 12mL ball grinders, ethyl acrylate (130mg,
1.3mmol), palladium (22.4mg, 0.1mmol), manganese dioxide (174mg, 2mmol), silica gel (525mg) adds 2 directly
Footpath is 10mm stainless steel ball, covers ball milling lid, and be put into ball mill makes mixture anti-with 600r/min per minute rotating speed operation
Answer 40 minutes.TLC (sampling is dissolved in ethyl acetate) tracks extent of reaction, after reaction terminates, by complete reaction mixture from grinding
Poured out in grinding jar, take out stainless steel ball, solid powder is directly used into petroleum ether and ethyl acetate (volume ratio 20:1) eluant, eluent
Column chromatography for separation is carried out, eluent of the gained containing target compound is evaporated off drying after solvent, obtains 3- ethoxycarbonyl-ethenyls -5-
Methoxy-Indole 100.5mg, yield is 41%.
Yellow solid, 74-76 DEG C of fusing point,1H NMR(400MHz,CDCl3) δ 8.59 (s, 1H), 7.88 (d, J=16.0Hz,
1H), 7.41 (d, J=2.4Hz, 1H), 7.30 (d, J=2.4Hz, 1H), 7.26 (d, J=8.8Hz, 1H), 6.93-6.87 (m,
1H), 6.35 (d, J=16.0Hz, 1H), 4.26 (q, J=7.1Hz, 2H), 3.88 (s, 3H) 1.35 (t, J=7.1Hz, 3H)；13C
NMR(100MHz,CD3Cl)δ168.2,155.2,138.3,132.0,129.2,125.8,113.1(2C),112.4(2C),
102.4,60.1,56.0,14.6.MS(ESI):246.6([M+H]+).
The preparation of the N- ethyl -3- ethoxycarbonyl-ethenyl indoles of embodiment 23
The addition N- ethylindoles (145mg, 1mmol) in 12mL ball grinders, ethyl acrylate (130mg, 1.3mmol),
Palladium (22.4mg, 0.1mmol), manganese dioxide (174mg, 2mmol), silica gel (525mg) adds 2 a diameter of 10mm
Stainless steel ball, cover ball milling lid, be put into ball mill makes mixture react 40 minutes with the operation of 600r/min per minute rotating speed.
TLC (sampling is dissolved in ethyl acetate) tracks extent of reaction, after reaction terminates, and complete reaction mixture is fallen from grinding pot
Go out, take out stainless steel ball, solid powder is directly used into petroleum ether and ethyl acetate (volume ratio 20:1) eluant, eluent carries out post layer
Analysis separation, eluent of the gained containing target compound is evaporated off drying after solvent, obtains N- ethyl -3- ethoxycarbonyl-ethenyl indoles
209mg, yield is 86%.
White solid：87-89 DEG C,1H NMR(400MHz,CDCl3)δ7.93-7.84[m,2H,including 7.88(d,
J=16Hz, 1H)], 7.40-7.20 (m, 4H), 6.39 (d, J=16.0Hz, 1H), 4.25 (q, J=7.1Hz, 2H), 4.18 (q,
J=7.3Hz, 2H), 1.50 (t, J=7.3Hz, 3H), 1.35 (t, J=7.1Hz, 3H)；13C NMR(100MHz,CDCl3)δ
168.1,137.9,137.0,131.2,126.1,122.7,121.1,120.6,112.4,112.1,109.9,60.0,41.4,
15.4,14.6.MS(ESI):244([M+H]+)；HMRS(ESI):C15H17NO2([M+H]+):calcd.244.1332,Found:
244.1332.
The preparation of the N- methyl -3- ethoxycarbonyl-ethenyl -5- nitro-indoles of embodiment 24
The nitro-indole (176mg, 1mmol) of addition N- ethyls -5 in 12mL ball grinders, ethyl acrylate (130mg,
1.3mmol), palladium (22.4mg, 0.1mmol), manganese dioxide (174mg, 2mmol), silica gel (525mg) adds 2 directly
Footpath is 10mm stainless steel ball, covers ball milling lid, and be put into ball mill makes mixture anti-with 600r/min per minute rotating speed operation
Answer 40 minutes.TLC (sampling is dissolved in ethyl acetate) tracks extent of reaction, after reaction terminates, by complete reaction mixture from grinding
Poured out in grinding jar, take out stainless steel ball, solid powder is directly used into petroleum ether and ethyl acetate (volume ratio 15:1) eluant, eluent
Column chromatography for separation is carried out, eluent of the gained containing target compound is evaporated off drying after solvent, obtains N- methyl -3- carbethoxyl group second
Alkenyl -5- nitro-indole 110mg, yield is 40%.
Yellow solid：137-139 DEG C,1H NMR(400MHz,CDCl3) δ 8.81 (d, J=2Hz, 1H), 8.21-8.16 (m,
1H), 7.83 (d, J=16.0Hz, 1H), 7.47 (s, 1H), 7.37 (d, J=8.8Hz 1H), 6.46 (d, J=16.0Hz, 1H),
4.28 (q, J=7.1Hz, 2H), 3.88 (s, 3H), 1.37 (t, J=7.1Hz, 3H)；13C NMR(100MHz,CDCl3)δ
166.9,142.1,140.1,135.4,134.5,124.9,118.1,117.0,114.9,113.9,109.7,60.5,34.0,
14.9.MS(ESI):275([M+H]+)；HMRS(ESI):C14H14N2NaO4([M+Na]+):calcd:297.0846,Found:
297.0859.
N- methyl -3- ethoxycarbonyl-ethenyl the indoles of comparative example 1 preparation (Angew.Chem.Int.Ed.2005,44,
3125.)
The addition N- methyl indols (131mg, 1mmol) in sealed reaction tube, ethyl acrylate (150mg,
1.5mmol), palladium (22.4mg, 0.1mmol), after oxygen bag insufflation gas, needle tubing injection DMSO (5mL) and trifluoro second
Sour (914mg, 8mmol), mixture is warming up to 60 DEG C and reacted 6.5 hours.TLC tracks extent of reaction, after reaction terminates, uses 20mL
Ester layer is collected in ethyl acetate dilute reaction solution, washing, ethyl acetate extraction (10mL × 3), and anhydrous sodium sulfate drying, decompression is steamed
Except after solvent use petroleum ether and ethyl acetate (volume ratio 15:1) eluant, eluent carries out column chromatography for separation, and gained contains target compound
Eluent be evaporated off after solvent dry, obtain N- methyl -3- ethoxycarbonyl-ethenyl indoles, yield 85%.(comparative example 9)
The preparation (Org.Lett.2012,14,5920.) of the positive butoxy carbonyl vinyl indoles of N- methyl -3- of comparative example 2
The addition N- methyl indols (131mg, 1mmol) in sealed reaction tube, ethyl acrylate (200mg,
2.0mmol), palladium (22.4mg, 0.1mmol), Salicylaldoxime (326mg, 1.8mmol), DMF (9mL), DMSO (1mL),
Reactant mixture is heated to 70 DEG C of stirring reactions 18 hours.TLC tracks extent of reaction, after reaction terminates, uses 20mL ethyl acetate
Ester layer is collected in dilute reaction solution, washing, ethyl acetate extraction (10mL × 3), and anhydrous sodium sulfate drying is removed under reduced pressure after solvent
With petroleum ether and ethyl acetate (volume ratio 15:1) eluant, eluent carries out column chromatography for separation, eluent of the gained containing target compound
It is evaporated off drying after solvent, obtains N- methyl -3- butoxy carbonyl vinyl indoles, yield 75%.(comparative example 16)
From above-mentioned comparative example, oxidation Heck coupling reactions are carried out under the conditions of mechanical ball mill and prepare 3- alkenyl indoles
Compound compared with heating response in conventional solution, in course of reaction without using the disagreeableness high boiler of environment as (DMF,
DMSO)；Reaction time greatly shortens (foreshortens to 45min by original 6.5h respectively；18h foreshortens to 40min)；Indoles and alkene
Reaction rate of charge by original 1：1.5~2 are reduced to equivalent reaction 1：1, reduce consumption of raw materials；Nothing after mechanical ball mill reaction
Solution extracting and washing processing need to be carried out, pure target product can be directly obtained through column chromatographic isolation and purification, relative ease, ring is operated
Border is friendly, and yield can reach high value.
Claims (6)
1. a kind of preparation method of the 3- alkenyl Benzazole compounds shown in formula (III), it is characterised in that described preparation method
For：
In stainless steel jar mill, add Olefination shown in the N- substituted indole compounds and formula (II) shown in raw material formula (I)
Compound, catalyst acetic acid palladium, oxidant manganese dioxide, grinding aid silica gel, abrasive media stainless steel ball, seal ball grinder, are placed in
Carried out in ball mill with 300~600r/min rotating speed after 30~60min of ball-milling reaction, reactant mixture is obtained through isolating and purifying
To the 3- alkenyl Benzazole compounds shown in formula (III)；
The ratio between amount for the material that feeds intake of olefin(e) compound shown in N- substituted indole compounds and formula (II) shown in the formula (I)
For 1：0.5~5.0；The ratio between amount for the material that feeds intake of N- substituted indole compounds shown in the catalyst acetic acid palladium and formula (I)
For 0.05~0.25：1；The amount of the oxidant manganese dioxide and the material that feeds intake of the N- substituted indole compounds shown in formula (I)
The ratio between be 1~3：1；
In formula (I) or formula (III), R1For hydrogen, methyl, ethyl or benzyl；R2For methyl, methoxyl group, chlorine, bromine or nitro；
In formula (II) or formula (III), R3For carbethoxyl group or butoxy carbonyl.
2. preparation method as claimed in claim 1, it is characterised in that the quality consumption of the grinding aid silica gel is formula (I) institute
2~8 times of the N- substituted indole compound quality shown.
3. preparation method as claimed in claim 1, it is characterised in that a diameter of the 8 of the abrasive media stainless steel ball~
12mm, the number of stainless steel ball is 2.
4. preparation method as claimed in claim 1, it is characterised in that N- substituted indole compounds shown in the formula (I) with
The ratio between amount for the material that feeds intake of olefin(e) compound shown in formula (II) is 1：1~3.0.
5. preparation method as claimed in claim 1, it is characterised in that the method that the reactant mixture is isolated and purified is：From
Stainless steel ball is taken out in reactant mixture, reactant mixture is subjected to column chromatography for separation, with petrol ether/ethyl acetate volume ratio 2
~50：1 mixed solvent is eluant, eluent, collects the eluent containing target compound, is evaporated off drying after solvent, produces formula (III)
Shown 3- alkenyl Benzazole compounds.
6. preparation method as claimed in claim 1, it is characterised in that described preparation method is：
In stainless steel jar mill, add Olefination shown in the N- substituted indole compounds and formula (II) shown in raw material formula (I)
Compound, catalyst acetic acid palladium, oxidant manganese dioxide, grinding aid silica gel, 2 8~12mm of diameter stainless steel ball, seal ball milling
Tank, is placed in ball mill and is carried out with 300~600r/min rotating speed after 30~60min of ball-milling reaction, taken from reactant mixture
Go out stainless steel ball, reactant mixture is subjected to column chromatography for separation, with petrol ether/ethyl acetate volume ratio 5~40：1 mixing is molten
Agent is eluant, eluent, collects the eluent containing target compound, is evaporated off drying after solvent, produces the 3- alkenyls Yin shown in formula (III)
Diindyl class compound；
The ratio between amount for the material that feeds intake of olefin(e) compound shown in N- substituted indole compounds and formula (II) shown in the formula (I)
For 1：1~3.0；The ratio between the catalyst acetic acid palladium and amount for the material that feeds intake of N- substituted indole compounds shown in formula (I) are
0.05~0.25：1；The amount of the material that feeds intake of N- substituted indole compounds shown in the oxidant manganese dioxide and formula (I) it
Than for 1~3：1；The quality consumption of the grinding aid silica gel is 2~5 times of the N- substituted indole compound quality shown in formula (I).
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