CN108864164A - A kind of synthetic method of the 2- alkynyl Benzazole compounds of level-one amine guiding - Google Patents
A kind of synthetic method of the 2- alkynyl Benzazole compounds of level-one amine guiding Download PDFInfo
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- CN108864164A CN108864164A CN201810703872.2A CN201810703872A CN108864164A CN 108864164 A CN108864164 A CN 108864164A CN 201810703872 A CN201810703872 A CN 201810703872A CN 108864164 A CN108864164 A CN 108864164A
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic System
- C07F7/02—Silicon compounds
- C07F7/08—Compounds having one or more C—Si linkages
- C07F7/0803—Compounds with Si-C or Si-Si linkages
- C07F7/081—Compounds with Si-C or Si-Si linkages comprising at least one atom selected from the elements N, O, halogen, S, Se or Te
- C07F7/0812—Compounds with Si-C or Si-Si linkages comprising at least one atom selected from the elements N, O, halogen, S, Se or Te comprising a heterocyclic ring
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic System
- C07F7/02—Silicon compounds
- C07F7/08—Compounds having one or more C—Si linkages
- C07F7/0803—Compounds with Si-C or Si-Si linkages
- C07F7/0825—Preparations of compounds not comprising Si-Si or Si-cyano linkages
- C07F7/0827—Syntheses with formation of a Si-C bond
Abstract
The invention discloses a kind of synthetic methods of the 2- alkynyl Benzazole compounds of level-one amine guiding.The synthetic method is：In the reactor, 2- (1 is addedHIndoles -1- base) amino benzenes compounds, alkynes halogen, palladium salt catalyst, alkali, solvent, it is stirred to react at 80 ~ 110 DEG C, reaction solution is isolated and purified, and 2- alkynyl Benzazole compounds are obtained.The method of the present invention has developed 2- (1HIndoles -1- base) aniline and alkynes halogen cross-coupling reaction, construct a series of 2- alkynyl Benzazole compounds of highly functionals, reaction takes water as a solvent, and meets the development need of green organic chemistry.In addition, raw material is simple and easy to get, safe operation, regioselectivity are good and substrate universality is extensively the main feature of reaction.
Description
Technical field
The invention belongs to 2- alkynyl Benzazole compounds fields, and in particular to a kind of 2- alkynyl indoles of level-one amine guiding
The synthetic method of compound.
Background technique
Benzazole compounds are widely present in nature as a kind of important heterocyclic compound, it is special chemically
Matter and bioactivity are concerned in fields such as drug, dyestuff, food, therefore are synthesized and modified this heterocyclic compounds organic
It is particularly significant in chemistry.The traditional method of building functionalized indoles' derivative is to carry out C-H halogenation to indoles classics occur again
Cross-coupling reaction.In recent years, flourishing along with c h bond activation, the method for the direct c h bond function dough of indoles is got over
To get over the favor by organic chemist.Alkynes is that participation is more as the important feature primitive in materials chemistry and synthesis chemistry
Therefore the superior reacting precursor of class conversion is had by the transition metal-catalyzed direct alkynylation reaction of the non-activated c h bond of indoles
Important meaning.
Under normal conditions, since the cloud density of 3 carbon of Benzazole compounds is higher than the cloud density of 2 carbon, make
It obtains compared with 2 carbon of 3 carbon and is prone to metalation.How it is highly selective realize 2 carbon of indoles alkynylation reaction still
It is challenging.It is combined in the method for 2- alkynyl Benzazole compounds in reported transition metal-catalyzed direct alkynyl
(L.Yang,L.Zhao,C.-J Li,Chem.Commun.2010,46,4184；G.L.Tolnai,S.Ganss,J.P.Brand,
Waser J.Org.Lett.2013,15,112；Z.-Z.Zhang,B.Liu,C.-Y.Wang,B.-F,
Shi.Org.Lett.2015,17,4094；T.Li,Z.Wang,W.-B.Qin,T.-B.Wen,ChemCatChem.2016,8,
2146；Z.Ruan,N.Sauermann,E.Manoni,L.Ackermann,Angew.Chem.Int.Ed.2017,129,
3220.), 3 of most indole substrate have steric group, and the diversity or raw material preparation for limiting substrate need multistep
Operation, or need to use and prepare dangerous and complicated high price alkynes iodine compound as raw material, Atom economy is poor.As it can be seen that hair
It is significant to open up green high-efficient, the method for highly selective synthesis 2- alkynyl Benzazole compounds.
In the past more than ten years, the diversity of homing device makes C-H functionalization strategies as the important of organic synthesis
Means have obtained huge development.In recent years, c h bond activate and then is handed over by level-one amine as guiding base
Fork coupling product cause researchers interest (Z.Liang, R.Feng, H.Yin, Y.Zhang.Org.Lett.2013,
15,4544；C.Suzuki,K.Morimoto,K.Hirano,T.Satoh,M.Miura.Adv.Synth.Catal.2014,
356,152；G.Jiang,W.Hu,J.Li,C.Zhu,W.Wu,H.Jiang.Chem.Commun.2018,54,1746.).In addition to
Except direct cross-coupling reaction, using exposed amino as homing device, cyclization, some biologies can also occur
Alkali, drug skeleton can by directly thus in a manner of construct (P.Bai, X.-F.Huang, G.-D.Xu, Z.-
Z.Huang.Org.Lett.2016,18,3058；T.U.Thikekar,C.-M.Sun.Adv.Synth.Catal.2017,359,
3388.), but the alkynylation reaction using level-one amine as homing device for indoles does not have been reported that also.In conclusion utilizing one
Grade amine realizes Benzazole compounds 2 alkynylation reactions, other than the novelty in methodology, application as guiding base
Prospect is also worthy of expecting.
Summary of the invention
It is an object of the invention in view of the shortcomings of the prior art and insufficient, a kind of 2- alkynyl of level-one amine guiding is provided
The synthetic method of Benzazole compounds.This method using 2- (1H- indoles -1- base) aniline simple and easy to get and alkynes halogen as raw material, with
Common palladium salt is as catalyst, and for cesium salt as alkali, water is solvent, the strategy using level-one amine as guiding base, selectively
The indole derivatives of 2 alkynyls are constructed, have high Atom economy, selectivity safety single, easy to operate and substrate suitable
The advantages that wide with property, has good application prospect in actual production and research.
The purpose of the present invention is achieved through the following technical solutions.
A kind of synthetic method of the 2- alkynyl Benzazole compounds of level-one amine guiding, comprises the following steps：
In the reactor, be added substrate 2- (1H- indoles -1- base) amino benzenes compounds, alkynes halogen, palladium salt catalyst, alkali and
Solvent is stirred to react at 80~110 DEG C, is cooled to room temperature after reaction, and product is isolated and purified, and obtains the 2- alkynyl
Benzazole compounds.
Further, the chemical equation of synthesis process is as follows：
In formula, R1For substituent group on indoles, R1Selected from hydrogen, 3- methyl, 4- methyl, 4- fluorine, 4- methoxyl group, 5- chlorine, 5- first
One or more of base, 5- cyano, 6- fluorine, 7- chlorine and 5,6- dichloro；
R2It is hydrogen, 4- methyl or 4,6- dimethyl for substituent group on aniline；
R3It is triisopropylsilyl for substituent group on alkynes halogen；
X is chlorine, bromine or iodine.
Further, 2- (1H- indoles -1- base) amino benzenes compounds are 2- (1H- indoles -1- base) aniline；It is described
Alkynes halogen is (2- bromoacetylene base) tri isopropyl silane.
Further, the palladium salt catalyst is one of palladium chloride, palladium acetate and four acetonitrile tetrafluoro boric acid palladiums or two
Kind or more.
Further, the molar ratio of the additional amount of the palladium salt catalyst and 2- (1H- indoles -1- base) amino benzenes compounds
It is 0.03~0.1:1.
Further, the additional amount of the alkynes halogen and the molar ratio of 2- (1H- indoles -1- base) amino benzenes compounds are 1.6
~3.0:1.
Further, the alkali be one of neopentanoic acid caesium, potassium acetate, cesium fluoride, sodium bicarbonate and saleratus or
It is two or more.
Further, the molar ratio of the additional amount of the alkali and 2- (1H- indoles -1- base) amino benzenes compounds be 2.0~
4.0:1。
Further, the solvent is water, toluene, 1,2- dichloroethanes or water and toluene is 2 by volume:1 mixing
Solvent.
Further, the time being stirred to react is 12~24 hours, preferably 20~24 hours.
Further, the operation isolated and purified is：Reaction solution is extracted with ethyl acetate, organic phase is merged, is used
Anhydrous magnesium sulfate dries, filters, and removes organic solvent under reduced pressure, obtains crude product, through column Chromatographic purification, obtains the 2- alkynyl indoles
Class compound.
Further, the eluent of column chromatography is petroleum ether and ethyl acetate by volume 20~150:1 it is mixed
Bonding solvent, preferably petroleum ether and ethyl acetate by volume 30~100:1 mixed solvent.
The reaction principle of synthetic method of the present invention be under the promotion of alkali, when amino is as homing device, 2- (1H- Yin
Diindyl -1- base) aniline and palladium salt catalyst occur coordination and form hexatomic ring palladium intermediate, and alkynes halogen carries out oxidation addition with it later,
It is eliminated again through reduction, obtains 2- alkynyl Benzazole compounds.
Compared with prior art, the invention has the advantages that and beneficial effect：
(1) present invention has developed the cross-coupling reaction structure of 2- (1H- indoles -1- base) aniline and alkynes halogen under amino guiding
The synthetic method of 2- alkynyl Benzazole compounds is built, and basic material 2- therein (1H- indoles -1- base) aniline can be by cheap
Adjacent Iodoaniline and indole synthesis, have that raw material is simple and easy to get, safe operation is simple, mild condition, Atom economy are high and
The wide feature of substrate applicability；
(2) synthetic method of the present invention operation is convenient and water can be used as solvent, environmentally protective, while to functional group
Tolerance is good, thus is expected to be applied to actual industrial production and further derivatization.
Detailed description of the invention
Fig. 1 and Fig. 2 is the hydrogen spectrogram and carbon spectrogram of 1 gained target product of embodiment respectively；
Fig. 3 and Fig. 4 is the hydrogen spectrogram and carbon spectrogram of 2 gained target product of embodiment respectively；
Fig. 5 and Fig. 6 is the hydrogen spectrogram and carbon spectrogram of 3 gained target product of embodiment respectively；
Fig. 7 and Fig. 8 is the hydrogen spectrogram and carbon spectrogram of 4 gained target product of embodiment respectively；
Fig. 9 and Figure 10 is the hydrogen spectrogram and carbon spectrogram of 5 gained target product of embodiment respectively；
Figure 11 and Figure 12 is the hydrogen spectrogram and carbon spectrogram of 6 gained target product of embodiment respectively；
Figure 13 and Figure 14 is the hydrogen spectrogram and carbon spectrogram of 7 gained target product of embodiment respectively；
Figure 15 and Figure 16 is the hydrogen spectrogram and carbon spectrogram of 8 gained target product of embodiment respectively；
Figure 17 and Figure 18 is the hydrogen spectrogram and carbon spectrogram of 9 gained target product of embodiment respectively；
Figure 19 and Figure 20 is the hydrogen spectrogram and carbon spectrogram of 10 gained target product of embodiment respectively；
Figure 21 and Figure 22 is the hydrogen spectrogram and carbon spectrogram of 11 gained target product of embodiment respectively；
Figure 23 and Figure 24 is the hydrogen spectrogram and carbon spectrogram of 12 gained target product of embodiment respectively；
Figure 25 and Figure 26 is the hydrogen spectrogram and carbon spectrogram of 13 gained target product of embodiment respectively；
Figure 27 and Figure 28 is the hydrogen spectrogram and carbon spectrogram of 14 gained target product of embodiment respectively；
Figure 29 and Figure 30 is the hydrogen spectrogram and carbon spectrogram of 15 gained target product of embodiment respectively.
Specific embodiment
Technical solution of the present invention is described in further detail below in conjunction with specific embodiments and drawings, but the present invention
Protection scope and embodiment it is without being limited thereto.
Embodiment 1
It is added in reaction tube 0.2 mM of 2- (1H- indoles -1- base) aniline, 0.006 mM of four acetonitrile tetrafluoro boric acid
Palladium, 0.4 mM of neopentanoic acid caesium, 0.32 mM of triisopropylsilyl alkynes bromine, 1.5 milliliters of water turn at 100 DEG C as solvent
It is stirred to react under fast 700rpm 24 hours；Stop stirring, 5mL water is added, is extracted with ethyl acetate 3 times, merge organic phase and makes
It is dried, filtered, is concentrated under reduced pressure with 0.5g anhydrous magnesium sulfate, then by column chromatographic isolation and purification, column chromatographic eluate used is
Volume ratio 100:1 petroleum ether:Ethyl acetate mixed solvent obtains target product, yield 80%.
Hydrogen spectrogram and carbon the spectrogram difference of gained target product are as depicted in figs. 1 and 2, and structural characterization data are as follows：
1H NMR(400MHz,CDCl3) δ=7.54 (d, J=7.6Hz, 1H), 7.16-7.04 (m, 4H), 6.93-6.91
(d, J=8.0Hz, 1H), 6.86 (s, 1H), 6.71-6.76 (m, 2H), 3.03 (s, 2H), 0.89 (s, 21H)；
13C NMR(100MHz,CDCl3) δ=144.1,137.2,130.0,129.6,127.3,123.6,123.1,
122.5,121.0,120.8,118.4,116.1,110.7,109.0,97.7,97.4,18.4,11.1；
IR(KBr)νmax 3870,3380,3049,2942,2865,2151,1615,1456,1311,1227,1002,
799,713cm-1；
HRMS(ESI)Calcd for C25H33N2Si[M+H]+:389.2408,Found 389.2412。
Infer that the structure of target product is as follows through above data：
Embodiment 2
It is added in reaction tube 0.2 mM of 2- (3- Methyl-1H-indole -1- base) aniline, 0.006 mM of four acetonitrile
Tetrafluoro boric acid palladium, 0.4 mM of neopentanoic acid caesium, 0.32 mM of triisopropylsilyl alkynes bromine, 1.5 milliliters of water as solvent,
It is stirred to react under revolving speed 700rpm 24 hours at 100 DEG C；Stop stirring, 5mL water is added, is extracted with ethyl acetate 3 times, is associated with
Machine phase is simultaneously dried, filtered using 0.5g anhydrous magnesium sulfate, is concentrated under reduced pressure, then passes through column chromatographic isolation and purification, column chromatography used
Eluent is volume ratio 100:1 petroleum ether:Ethyl acetate mixed solvent obtains target product, yield 86%.
Hydrogen spectrogram and carbon the spectrogram difference of gained target product are as shown in Figure 3 and Figure 4, and structural characterization data are as follows：
1H NMR(400MHz,CDCl3) δ=7.58 (d, J=7.7Hz, 1H), 7.22-7.11 (m, 4H), 6.99 (d, J=
8.0Hz,1H),6.82-6.77(m,2H),3.28(s,2H),2.47(s,3H),0.98(s,21H)；
13C NMR(100MHz,CDCl3) δ=144.0,136.9,130.0,129.3,127.6,123.8,123.4,
120.7,120.1,119.3,118.7,118.4,116.1,110.6,99.6,97.3,18.5,11.1,9.9；
IR(KBr)νmax 3679,3052,2945,2865,2148,1697,1597,1505,1454,1308,1225,
797,718cm-1；
HRMS(ESI)Calcd for C26H35N2Si[M+H]+:403.2564,Found 403.2569。
Infer that the structure of target product is as follows through above data：
Embodiment 3
It is added in reaction tube 0.2 mM of 2- (4- Methyl-1H-indole -1- base) aniline, 0.006 mM of four acetonitrile
Tetrafluoro boric acid palladium, 0.4 mM of neopentanoic acid caesium, 0.32 mM of triisopropylsilyl alkynes bromine, 1.5 milliliters of water as solvent,
It is stirred to react under revolving speed 700rpm 24 hours at 100 DEG C；Stop stirring, 5mL water is added, is extracted with ethyl acetate 3 times, is associated with
Machine phase is simultaneously dried, filtered using 0.5g anhydrous magnesium sulfate, is concentrated under reduced pressure, then passes through column chromatographic isolation and purification, column chromatography used
Eluent is volume ratio 100:1 petroleum ether:Ethyl acetate mixed solvent obtains target product, yield 67%.
Hydrogen spectrogram and carbon the spectrogram difference of gained target product are as shown in Figure 5 and Figure 6, and structural characterization data are as follows：
1H NMR(400MHz,CDCl3) δ=7.25-7.21 (m, 1H), 7.17 (dd, J=7.7Hz, 1H), 7.14-7.10
(t, J=7.8Hz, 1H), 7.00 (s, 1H), 6.97 (d, J=7.2Hz, 1H), 6.87-6.80 (m, 3H), 3.50 (s, 2H),
2.58(s,3H),0.98(s,21H)；
13C NMR(100MHz,CDCl3) δ=144.0,137.0,130.6,130.0,129.6,127.2,123.8,
123.3,121.9,120.9,118.4,116.1,108.4,107.6,97.8,97.2,18.6,18.4,11.1；
IR(KBr)νmax 3732,3671,2941,2862,2150,1620,1504,1308,1228,796,713cm-1；
HRMS(ESI)Calcd for C26H35N2Si[M+H]+:403.2564,Found 403.2566。
Infer that the structure of target product is as follows through above data：
Embodiment 4
It is added in reaction tube 0.2 mM of 2- (the fluoro- 1H- indoles -1- base of 4-) aniline, 0.006 mM of four acetonitrile four
Fluoboric acid palladium, 0.4 mM of neopentanoic acid caesium, 0.32 mM of triisopropylsilyl alkynes bromine, 1.5 milliliters of water are as solvent, 100
It is stirred to react under revolving speed 700rpm 24 hours at DEG C；Stop stirring, 5mL water is added, is extracted with ethyl acetate 3 times, merges organic
It is dried, filtered mutually and using 0.5g anhydrous magnesium sulfate, is concentrated under reduced pressure, then by column chromatographic isolation and purification, column chromatography used is washed
De- liquid is volume ratio 100:1 petroleum ether:Ethyl acetate mixed solvent obtains target product, yield 74%.
Hydrogen spectrogram and carbon the spectrogram difference of gained target product are as shown in Figure 7 and Figure 8, and structural characterization data are as follows：
1H NMR(400MHz,CDCl3) δ=7.25-7.21 (m, 1H), 7.17-7.15 (m, 1H), 7.12-7.07 (m,
1H), 7.01 (s, 1H), 6.85-6.77 (m, 4H), 3.34 (s, 2H), 0.96 (d, J=2.4Hz, 21H)；
13C NMR(100MHz,CDCl3) δ=156.1 (d, J=248.8Hz), 143.9,139.4 (d, J=10.5Hz),
129.9 (d, J=4.7Hz), 124.1 (d, J=7.7Hz), 122.8,122.6,118.6,116.6 (d, J=22.8Hz),
(116.3,106.8 d, J=3.8Hz), 105.5,105.3,104.8,97.9,97.0,18.4,11.1.
IR(KBr)νmax 3388,2945,2154,1687,1488,1313,1234,788,675cm-1；
HRMS(ESI)Calcd for C25H32FN2Si[M+H]+:407.2313,Found 407.2319。
Infer that the structure of target product is as follows through above data：
Embodiment 5
It is added in reaction tube 0.2 mM of 2- (the chloro- 1H- indoles -1- base of 4-) aniline, 0.006 mM of four acetonitrile four
Fluoboric acid palladium, 0.4 mM of neopentanoic acid caesium, 0.32 mM of triisopropylsilyl alkynes bromine, 1.5 milliliters of water are as solvent, 100
It is stirred to react under revolving speed 700rpm 20 hours at DEG C；Stop stirring, 5mL water is added, is extracted with ethyl acetate 3 times, merges organic
It is dried, filtered mutually and using 0.5g anhydrous magnesium sulfate, is concentrated under reduced pressure, then by column chromatographic isolation and purification, column chromatography used is washed
De- liquid is volume ratio 100:1 petroleum ether:Ethyl acetate mixed solvent obtains target product, yield 82%.
Hydrogen spectrogram and carbon the spectrogram difference of gained target product are as shown in Figure 9 and Figure 10, and structural characterization data are as follows：
1H NMR(400MHz,CDCl3) δ=7.24-7.20 (m, 1H), 7.15-7.12 (m, 2H), 7.08 (t, J=
7.8Hz, 1H), 7.04 (s, 1H), 6.89 (d, J=8.0Hz, 1H), 6.83-6.78 (m, 2H), 3.44 (s, 2H), 0.96 (d, J
=2.3Hz, 21H)；
13C NMR(100MHz,CDCl3) δ=143.9,137.8,129.9,129.8,126.2,126.1,124.1,
123.2,122.6,120.5,118.5,116.2,109.4,107.3,98.3,97.0,18.4,11.1.
IR(KBr)νmax 2946,2154,1613,1503,1309,1228,796,713cm-1；
HRMS(ESI)Calcd for C25H32ClN2Si[M+H]+,423.2018,found 423.2024。
Infer that the structure of target product is as follows through above data：
Embodiment 6
It is added in reaction tube 0.2 mM of 2- (4- methoxyl group -1H- indoles -1- base) aniline, 0.006 mM of tetrem
Nitrile tetrafluoro boric acid palladium, 0.4 mM of neopentanoic acid caesium, 0.32 mM of triisopropylsilyl alkynes bromine, 1.5 milliliters of water as solvent,
It is stirred to react under revolving speed 700rpm 24 hours at 100 DEG C；Stop stirring, 5mL water is added, is extracted with ethyl acetate 3 times, merges
Organic phase is simultaneously dried, filtered using 0.5g anhydrous magnesium sulfate, is concentrated under reduced pressure, then passes through column chromatographic isolation and purification, column layer used
Analysis eluent is volume ratio 60:1 petroleum ether:Ethyl acetate mixed solvent obtains target product, yield 56%.
The hydrogen spectrogram and carbon spectrogram of gained target product are distinguished as is illustrated by figs. 11 and 12, the following institute of structural characterization data
Show：
1H NMR(400MHz,CDCl3) δ=7.23-7.19 (m, 1H), 7.16 (d, J=7.7Hz, 1H), 7.11 (t, J=
8.0Hz, 1H), 7.05 (s, 1H), 6.83-6.78 (m, 2H), 6.62 (d, J=8.4Hz, 1H), 6.53 (d, J=7.6Hz, 1H),
3.96(s,3H),3.49(s,2H),0.96(s,21H)；
13C NMR(100MHz,CDCl3) δ=153.4,144.0,138.5,129.9,129.56,124.6,123.2,
121.1,118.4,118.2,116.1,106.6,104.0 100.4,97.8,96.8,55.4,18.4,11.1；
IR(KBr)νmax 3378,2940,2149,1610,1494,1313,1250,798,675cm-1；
HRMS(ESI)Calcd for C26H35N2OSi[M+H]+:419.2513,Found 419.2514。
Infer that the structure of target product is as follows through above data：
Embodiment 7
It is added in reaction tube 0.2 mM of 2- (the chloro- 1H- indoles -1- base of 5-) aniline, 0.006 mM of four acetonitrile four
Fluoboric acid palladium, 0.4 mM of neopentanoic acid caesium, 0.32 mM of triisopropylsilyl alkynes bromine, 1.5 milliliters of water are as solvent, 100
It is stirred to react under revolving speed 700rpm 24 hours at DEG C；Stop stirring, 5mL water is added, is extracted with ethyl acetate 3 times, merges organic
It is dried, filtered mutually and using 0.5g anhydrous magnesium sulfate, is concentrated under reduced pressure, then by column chromatographic isolation and purification, column chromatography used is washed
De- liquid is volume ratio 100:1 petroleum ether:Ethyl acetate mixed solvent obtains target product, yield 78%.
The hydrogen spectrogram and carbon spectrogram of gained target product distinguish as shown in Figure 13 and Figure 14, the following institute of structural characterization data
Show：
1H NMR(400MHz,CDCl3) δ=7.58 (d, J=2.0Hz, 1H), 7.24-7.20 (m, 1H), 7.14-7.11
(m, 2H), 6.91 (d, J=8.4Hz, 1H), 6.86 (s, 1H), 6.83-6.78 (m, 2H), 3.45 (s, 2H), 0.95 (d, J=
2.0Hz,21H)；
13C NMR(001MHz,CDCl3) δ=143.9,135.5,129.9,129.8,128.2,126.5,123.9,
123.8,122.6,120.2,118.5,116.2,111.8,108.3,98.3,97.0,18.4,11.1；
IR(KBr)νmax 3379,2941,2152,1616,1451,1311,1228,796,717cm-1；
HRMS(ESI)Calcd for C25H32ClN2Si[M+H]+:423.2018,Found 423.2012。
Infer that the structure of target product is as follows through above data：
Embodiment 8
It is added in reaction tube 0.2 mM of 2- (5- Methyl-1H-indole -1- base) aniline, 0.006 mM of four acetonitrile
Tetrafluoro boric acid palladium, 0.4 mM of neopentanoic acid caesium, 0.32 mM of triisopropylsilyl alkynes bromine, 1.5 milliliters of water as solvent,
It is stirred to react under revolving speed 700rpm 24 hours at 100 DEG C；Stop stirring, 5mL water is added, is extracted with ethyl acetate 3 times, is associated with
Machine phase is simultaneously dried, filtered using 0.5g anhydrous magnesium sulfate, is concentrated under reduced pressure, then passes through column chromatographic isolation and purification, column chromatography used
Eluent is volume ratio 100:1 petroleum ether:Ethyl acetate mixed solvent obtains target product, yield 76%.
The hydrogen spectrogram and carbon spectrogram of gained target product distinguish as shown in Figure 15 and Figure 16, the following institute of structural characterization data
Show：
1H NMR(400MHz,CDCl3) δ=7.39 (s, 1H), 7.22-7.17 (m, 1H), 7.16-7.14 (m, 1H),
7.03-7.00 (m, 1H), 6.89 (d, J=8.4Hz, 1H), 6.85 (s, 1H), 6.81-6.77 (m, 2H), 3.46 (s, 2H),
2.43(s,3H),0.96(s,21H)；
13C NMR(100MHz,CDCl3) δ=144.1,135.6,130.1,130.0,129.5,127.5,125.4,
123.2,122.4,120.5,118.4,116.1,110.4,108.5,97.8,97.1,21.4,18.4,11.1；
IR(KBr)νmax 2945,2150,1615,1458,1308,1228,797,716cm-1；
HRMS(ESI)Calcd for C26H35N2Si[M+H]+:403.2564,Found 403.2568。
Infer that the structure of target product is as follows through above data：
Embodiment 9
It is added in reaction tube 0.2 mM of 2- (5- cyano-1 H-indol -1- base) aniline, 0.006 mM of four acetonitrile
Tetrafluoro boric acid palladium, 0.4 mM of neopentanoic acid caesium, 0.32 mM of triisopropylsilyl alkynes bromine, 1.5 milliliters of water as solvent,
It is stirred to react under revolving speed 700rpm 24 hours at 100 DEG C；Stop stirring, 5mL water is added, is extracted with ethyl acetate 3 times, is associated with
Machine phase is simultaneously dried, filtered using 0.5g anhydrous magnesium sulfate, is concentrated under reduced pressure, then passes through column chromatographic isolation and purification, column chromatography used
Eluent is volume ratio 50:1 petroleum ether:Ethyl acetate mixed solvent obtains target product, yield 71%.
The hydrogen spectrogram and carbon spectrogram of gained target product distinguish as shown in Figure 17 and Figure 18, the following institute of structural characterization data
Show：
1H NMR(400MHz,CDCl3) δ=7.97 (d, J=0.6,1H), 7.39-7.39 (m, 1H), 7.29-7.22 (m,
1H), 7.16-7.11 (m, 1H), 7.05 (d, J=8.6Hz, 1H), 6.98 (s, 1H), 6.88-6.80 (m, 2H), 3.33 (s,
2H), 0.96 (d, J=3.0Hz, 21H)
13C NMR(100MHz,CDCl3) δ=143.8,138.6,130.3,129.6,127.0,126.4,126.2,
125.0,121.8,120.2,118.6,116.4,111.6,109.0,104.0,99.7,96.2,18.3,11.0；
IR(KBr)νmax 3373,2942,2222,1615,1460,1312,1230,797,719cm-1；
HRMS(ESI)Calcd for C26H32N3Si[M+H]+:414.2360,Found 414.2361。
Infer that the structure of target product is as follows through above data：
Embodiment 10
It is added in reaction tube 0.2 mM of 2- (the fluoro- 1H- indoles -1- base of 6-) aniline, 0.006 mM of four acetonitrile four
Fluoboric acid palladium, 0.4 mM of neopentanoic acid caesium, 0.32 mM of triisopropylsilyl alkynes bromine, 1.5 milliliters of water are as solvent, 100
It is stirred to react under revolving speed 700rpm 24 hours at DEG C；Stop stirring, 5mL water is added, is extracted with ethyl acetate 3 times, merges organic
It is dried, filtered mutually and using 0.5g anhydrous magnesium sulfate, is concentrated under reduced pressure, then by column chromatographic isolation and purification, column chromatography used is washed
De- liquid is volume ratio 100:1 petroleum ether:Ethyl acetate mixed solvent obtains target product, yield 85%.
The hydrogen spectrogram and carbon spectrogram of gained target product are distinguished as illustrated in figures 19 and 20, the following institute of structural characterization data
Show：
1H NMR(400MHz,CDCl3) δ=7.54-7.50 (m, 1H), 7.24-7.20 (m, 1H), 7.15-7.13 (m,
1H),6.93-6.87(m,2H),6.83-6.78(m,2H),6.70-6.67(m,1H),3.48(s,2H),0.96(s,21H).
13C NMR(100MHz,CDCl3) δ=161.2 (d, J=240.7Hz), 143.9,137.4 (d, J=12.3Hz),
129.81 (d, J=8.1Hz), 123.6,123.1 (d, J=4.1Hz), 122.6,121.8 (d, J=10.0Hz), 118.5,
(116.2,109.8 d, J=24.9Hz), 108.9,97.6,97.3,92,2,97.0,18.4,11.1；
IR(KBr)νmax 2944,2150,1612,1496,1307,1230,799,716cm-1；
HRMS(ESI)Calcd for C25H32FN2Si[M+H]+:407.2313,Found 407.2318。
Infer that the structure of target product is as follows through above data：
Embodiment 11
It is added in reaction tube 0.2 mM of 2- (the chloro- 1H- indoles -1- base of 7-) aniline, 0.006 mM of four acetonitrile four
Fluoboric acid palladium, 0.4 mM of neopentanoic acid caesium, 0.32 mM of triisopropylsilyl alkynes bromine, 1.5 milliliters of water are as solvent, 100
It is stirred to react under revolving speed 700rpm 24 hours at DEG C；Stop stirring, 5mL water is added, is extracted with ethyl acetate 3 times, merges organic
It is dried, filtered mutually and using 0.5g anhydrous magnesium sulfate, is concentrated under reduced pressure, then by column chromatographic isolation and purification, column chromatography used is washed
De- liquid is volume ratio 100:1 petroleum ether:Ethyl acetate mixed solvent obtains target product, yield 70%.
The hydrogen spectrogram and carbon spectrogram of gained target product are distinguished as shown in figure 21 and figure, the following institute of structural characterization data
Show：
1H NMR(400MHz,CDCl3) δ=7.51 (d, J=7.6,1H), 7.20 (t, J=7.6Hz, 1H), 7.12-7.17
(m, 2H), 7.03 (t, J=7.8Hz, 1H), 6.93 (s, 1H), 6.77 (t, J=7.8Hz, 2H), 3.43 (s, 2H), 0.95 (s,
21H)；
13C NMR(100MHz,CDCl3) δ=145.0,132.4,130.5,130.0,129.8,125.0,124.6,
124.5,121.3,119.7,117.9,117.1,115.5,109.2,98.3,96.8,18.4,11.0；
IR(KBr)νmax 2945,2154,1693,1606,1308,1226,796,713cm-1；
HRMS(ESI)Calcd for C25H32ClN2Si[M+H]+,423.2018,Found 423.2021。
Infer that the structure of target product is as follows through above data：
Embodiment 12
It is added in reaction tube 0.2 mM of 2- (the chloro- 1H- indoles -1- base of 5,6- bis-) aniline, 0.006 mM of tetrem
Nitrile tetrafluoro boric acid palladium, 0.4 mM of neopentanoic acid caesium, 0.32 mM of triisopropylsilyl alkynes bromine, 1.5 milliliters of water as solvent,
It is stirred to react under revolving speed 700rpm 24 hours at 100 DEG C；Stop stirring, 5mL water is added, is extracted with ethyl acetate 3 times, merges
Organic phase is simultaneously dried, filtered using 0.5g anhydrous magnesium sulfate, is concentrated under reduced pressure, then passes through column chromatographic isolation and purification, column layer used
Analysis eluent is volume ratio 100:1 petroleum ether:Ethyl acetate mixed solvent obtains target product, yield 71%.
The hydrogen spectrogram and carbon spectrogram of gained target product are distinguished as shown in figure 23 and figure 24, the following institute of structural characterization data
Show：
1H NMR(400MHz,CDCl3) δ=7.68 (s, 1H), 7.26-7.22 (m, 1H), 7.13-7.10 (m, 2H),
6.84-6.79 (m, 3H), 3.47 (s, 2H), 0.95 (d, J=2.4Hz, 21H)
13C NMR(100MHz,CDCl3) δ=143.9,135.9,130.1,129.7,127.7,126.7,125.0,
124.5,122.1,121.7,118.6,116.3,112.2,108.0,99.0,96.6,18.4,11.0；
IR(KBr)νmax 2950,1612,1306,1227,795,716cm-1；
HRMS(ESI)Calcd for C25H31Cl2N2Si[M+H]+,457.1628,Found 457.1621。
Infer that the structure of target product is as follows through above data：
Embodiment 13
It is added in reaction tube 0.2 mM of 2- (- 1H- indoles -1- base) -4- methylaniline, 0.006 mM of four acetonitrile
Tetrafluoro boric acid palladium, 0.4 mM of neopentanoic acid caesium, 0.32 mM of triisopropylsilyl alkynes bromine, 1.5 milliliters of water as solvent,
It is stirred to react under revolving speed 700rpm 24 hours at 100 DEG C；Stop stirring, 5mL water is added, is extracted with ethyl acetate 3 times, is associated with
Machine phase is simultaneously dried, filtered using 0.5g anhydrous magnesium sulfate, is concentrated under reduced pressure, then passes through column chromatographic isolation and purification, column chromatography used
Eluent is volume ratio 100:1 petroleum ether:Ethyl acetate mixed solvent obtains target product, yield 60%.
The hydrogen spectrogram and carbon spectrogram of gained target product are distinguished as illustrated in figs. 25 and 26, the following institute of structural characterization data
Show：
1H NMR(400MHz,CDCl3) δ=7.61 (d, J=7.8,1H), 7.19 (t, J=7.5Hz, 1H), 7.13 (t, J
=7.3Hz, 1H), 7.03-6.98 (m, 3H), 6.92 (s, 1H), 6.74 (d, J=8.4Hz, 1H), 3.07 (s, 2H), 2.24 (s,
3H),0.97(s,21H).
13C NMR(100MHz,CDCl3) δ=141.4,137.1,130.2,127.8,127.2,123.6,123.1,
122.5,121.0,120.7,116.3,110.8,108.9,97.8,97.3,20.2,18.4,11.1；
IR(KBr)νmax 3673,1695,1306,1226,796,715cm-1；
HRMS(ESI)Calcd for C26H35N2Si[M+H]+,403.2564,found 403.2569。
Infer that the structure of target product is as follows through above data：
Embodiment 14
It is added in reaction tube 0.2 mM of 2- (- 1H- indoles -1- base) -4,6- dimethylaniline, 0.006 mM four
Acetonitrile tetrafluoro boric acid palladium, 0.4 mM of neopentanoic acid caesium, 0.32 mM of triisopropylsilyl alkynes bromine, 1.5 milliliters of water are as molten
Agent is stirred to react 24 hours at 100 DEG C under revolving speed 700rpm；Stop stirring, 5mL water be added, is extracted with ethyl acetate 3 times,
Merge organic phase and dried, filtered using 0.5g anhydrous magnesium sulfate, is concentrated under reduced pressure, then by column chromatographic isolation and purification, it is used
Column chromatographic eluate is volume ratio 100:1 petroleum ether:Ethyl acetate mixed solvent obtains target product, yield 73%.
The hydrogen spectrogram and carbon spectrogram of gained target product are respectively as shown in Figure 27 and Figure 28, the following institute of structural characterization data
Show：
1H NMR(400MHz,CDCl3) δ=7.61 (d, J=8.0,1H), 7.19-7.10 (m, 2H), 6.99 (d, J=
8.0,1H), 6.93 (d, J=8.0,2H), 6.85 (s, 1H), 3.04 (s, 2H), 2.22 (s, 3H), 2.17 (s, 3H), 0.95 (s,
21H)；
13C NMR(100MHz,CDCl3) δ=139.8,137.4,131.4,127.7,127.2,127.0,123.5,
123.4,122.9,122.6,120.9,120.7,110.8,108.7,97.9,97.1,20.2,18.4,17.5,11.1；
IR(KBr)νmax 3385,2941,2151,1694,1599,1312,1228,797,717cm-1；
HRMS(ESI)Calcd for C27H37N2Si[M+H]+,417.2721,Found 417.2727。
Infer that the structure of target product is as follows through above data：
Embodiment 15
It is added in reaction tube 0.2 mM of 2- (- 1H- pyrroles -1- base)-aniline, 0.006 mM of four acetonitrile tetrafluoro boron
Sour palladium, 0.8 mM of neopentanoic acid caesium, 0.6 mM of triisopropylsilyl alkynes bromine, 1.5 milliliters of water are as solvent, at 100 DEG C
It is stirred to react under revolving speed 700rpm 24 hours；Stop stirring, 5mL water is added, is extracted with ethyl acetate 3 times, merges organic phase simultaneously
It is dried, filtered, is concentrated under reduced pressure using 0.5g anhydrous magnesium sulfate, then pass through column chromatographic isolation and purification, column chromatographic eluate used
For volume ratio 100:1 petroleum ether:Ethyl acetate mixed solvent obtains target product, yield 33%.
The hydrogen spectrogram and carbon spectrogram of gained target product distinguish as shown in Figure 29 and Figure 30, the following institute of structural characterization data
Show：
1H NMR(400MHz,CDCl3) δ=7.13-7.08 (m, 2H), 6.73-6.69 (m, 2H), 6.49 (s, 2H), 3.50
(s,2H),0.92(s,42H)；
13C NMR(100MHz,CDCl3) δ=143.8,129.6,129.5,124.3,118.1,118.0,116.0,
115.0,97.5,94.8,18.4,11.1；
IR(KBr)νmax 2944,2145,1460,1306,1229,794,716cm-1；
HRMS(ESI)Calcd for C35H51N2Si2[M+H]+,519.3585,found 519.3591。
Infer that the structure of target product is as follows through above data：
The above embodiment is a preferred embodiment of the present invention, but embodiments of the present invention are not by above-described embodiment
Limitation, other any changes, modifications, substitutions, combinations, simplifications made without departing from the spirit and principles of the present invention,
It should be equivalent substitute mode, be included within the scope of the present invention.
Claims (10)
1. a kind of synthetic method of the 2- alkynyl Benzazole compounds of level-one amine guiding, which is characterized in that comprise the following steps：
In the reactor, addition substrate 2- (1H- indoles -1- base) amino benzenes compounds, alkynes halogen, palladium salt catalyst, alkali and solvent,
It is stirred to react at 80~110 DEG C, is cooled to room temperature after reaction, product is isolated and purified, and the 2- alkynyl indoles is obtained
Class compound.
2. synthetic method according to claim 1, which is characterized in that the following institute of the chemical equation of synthesis process
Show：
In formula, R1Selected from hydrogen, 3- methyl, 4- methyl, 4- fluorine, 4- methoxyl group, 5- chlorine, 5- methyl, 5- cyano, 6- fluorine, 7- chlorine and 5,
One or more of 6- dichloro；
R2For hydrogen, 4- methyl or 4,6- dimethyl；
R3For triisopropylsilyl；
X is chlorine, bromine or iodine.
3. synthetic method according to claim 1, which is characterized in that 2- (1H- indoles -1- base) amino benzenes compounds
For 2- (1H- indoles -1- base) aniline；The alkynes halogen is (2- bromoacetylene base) tri isopropyl silane.
4. synthetic method according to claim 1 or 2, which is characterized in that the palladium salt catalyst is palladium chloride, palladium acetate
One or more of with four acetonitrile tetrafluoro boric acid palladiums.
5. synthetic method according to claim 1 or 2, which is characterized in that the additional amount and 2- of the palladium salt catalyst
The molar ratio of (1H- indoles -1- base) amino benzenes compounds is 0.03~0.1:1.
6. synthetic method according to claim 1 or 2, which is characterized in that the additional amount and 2- (1H- indoles-of the alkynes halogen
1- yl) amino benzenes compounds molar ratio be 1.6~3.0:1.
7. synthetic method according to claim 1 or 2, which is characterized in that the alkali is neopentanoic acid caesium, potassium acetate, fluorination
One or more of caesium, sodium bicarbonate and saleratus；The additional amount and 2- (1H- indoles -1- base) aniline of the alkali
The molar ratio of class compound is 2.0~4.0:1.
8. synthetic method according to claim 1 or 2, which is characterized in that the solvent is water, toluene or water and toluene
Mixed solvent.
9. synthetic method according to claim 1 or 2, which is characterized in that the time being stirred to react is 20~24 small
When.
10. synthetic method according to claim 1 or 2, which is characterized in that the operation isolated and purified is：It will reaction
Liquid is extracted with ethyl acetate, and merges organic phase, is dried, filtered using anhydrous magnesium sulfate, remove organic solvent under reduced pressure, obtained and slightly produce
Object obtains the 2- alkynyl Benzazole compounds through column Chromatographic purification.
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| WO2020177347A1 (en) * | 2019-03-04 | 2020-09-10 | 华南理工大学 | Oxygen-guided synthesis method for 7-alkynyl indole compound |
| CN114874126A (en) * | 2022-05-10 | 2022-08-09 | 华南理工大学 | Synthetic method of 3-bromoindole compound |
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| CN106279236A (en) * | 2016-08-11 | 2017-01-04 | 南京理工大学 | A kind of method of synthesis 2 triisopropylsilyl acetylene Benzazole compounds |
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| CN106279236A (en) * | 2016-08-11 | 2017-01-04 | 南京理工大学 | A kind of method of synthesis 2 triisopropylsilyl acetylene Benzazole compounds |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
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| WO2020177347A1 (en) * | 2019-03-04 | 2020-09-10 | 华南理工大学 | Oxygen-guided synthesis method for 7-alkynyl indole compound |
| CN114874126A (en) * | 2022-05-10 | 2022-08-09 | 华南理工大学 | Synthetic method of 3-bromoindole compound |
| CN114874126B (en) * | 2022-05-10 | 2024-01-12 | 华南理工大学 | Synthetic method of 3-bromoindole compound |
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