CN108218762A - A kind of synthetic method of 2 quaternary carbons indoles -3- ketone compounds - Google Patents
A kind of synthetic method of 2 quaternary carbons indoles -3- ketone compounds Download PDFInfo
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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
- C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
- C07D209/32—Oxygen atoms
- C07D209/36—Oxygen atoms in position 3, e.g. adrenochrome
Abstract
The present invention relates to the methods of a kind of efficient and easy to operate 23 ketone compounds of quaternary carbon indoles of synthesis.This method is using peroxide as oxidant, intermolecular reaction occurs using 2 substituted indoles and Benzazole compounds, 2 substituted indole of substrate and Benzazole compounds are added in i.e. into the reaction bulb equipped with oxidant and solvent, 1 ~ 48 h is reacted in 60 ~ 140 DEG C of oil baths, it is cooled to room temperature after reaction, it adds in saturated sodium bicarbonate and reaction is quenched, extraction and separation are concentrated to give 23 ketone compounds of quaternary carbon indoles of product again, its yield is up to 96%, it is cheap with raw material, it is easy to operate, the advantages that substrate universality is good and reaction yield is high.
Description
Technical field
The present invention relates to a kind of simple and effective and in neutral conditions, directly Benzazole compounds are turned in green solvent
The method for turning to 2 quaternary carbon indoles -3- ketone compounds.
Background technology
Indoles -3- ketone is the unique substructure and structure being widely present in natural alkaloid and bioactive molecule
The core of many biologically active alkaloids and medicinal activity compound.Such as (-)-isatisine A, (-)-
Isatisine A acetonide, strobilanthoside A, (-)-trigonoliimine C, (+)-austamide,
With the compounds such as halichrome A（J. Nat. Prod., 2014, 77(12), 2590）.Therefore, exploitation is used to build 2,
The convenience and green method of the disubstituted indoline -3- ketone of 2- have important theoretical and practical significance.
The synthetic method of 2 3- indole ketone compounds with quaternary carbon chiral centre is broadly divided into three classes, one kind be with
Non- benzazole precursor（J. Catal., 2014, 315(1), 33）By being cyclized the derivative to build indolone；Second class is
With Benzazole compounds（J. Org. Chem., 2004, 69(6), 2200; Acs. Catal., 2016, 6(10),
6853; J. Org. Chem., 2017, 82(4), 2107; Org. Biomol. Chem., 2017, 15(2),
442.）It synthesizes to obtain by unimolecule or bimolecular reaction for raw material；Third class is with 3- indole ketones（Adv. Synth. Catal., 2011, 353(4), 563; Chem. Sci., 2011, 2(7), 1344）Pass through for substrate all kinds of
It reacts to synthesize to obtain.But the above method usually has the disadvantages that, such as substrate spectrum is limited, the yield of reaction and selection
Property it is relatively low or use expensive reagent.Therefore, probe into one it is simple and effective and in neutral conditions directly by indoles chemical combination
The method that object is converted into 2 quaternary carbon indoles -3- ketone is significant.
Invention content
The technical problem to be solved by the present invention is to study one it is simple and effective and in neutral conditions in green solvent directly
Benzazole compounds are converted into the method for 2 quaternary carbon indoles -3- ketone.
A kind of synthetic method of 2 quaternary carbons indoles -3- ketone compounds, it is characterised in that equipped with oxidant and
Formula is added in the reaction bulb of solvent（Ⅰ）Shown substrate 2- substituted indoles and formula（Ⅱ）Shown Benzazole compounds, 60 ~
1 ~ 48 h is reacted in 140 DEG C of oil baths, is cooled to room temperature after reaction, saturated sodium bicarbonate is added in and reaction is quenched, then extract point
From being concentrated to give formula（Ⅲ）Shown 2 quaternary carbon indoles -3- ketone compounds of product,
,
In formula, R1、R3For hydrogen atom or alkyl, R2For hydrogen atom, alkyl, aryl, R4For hydrogen atom, alkyl, halogen, aryl, benzyl
Oxygroup, nitro or cyano.
The synthetic method of 2 quaternary carbon indoles -3- ketone compounds, it is characterised in that solvent is selected from Isosorbide-5-Nitrae-dioxy six
The mixture of one or more of ring, acetonitrile, toluene, water arbitrary proportion, preferably water.
The synthetic method of 2 quaternary carbon indoles -3- ketone compounds, it is characterised in that reaction temperature 60-120
DEG C, preferably 100 DEG C, the reaction time is 5-48 hours, preferably 24 hours.
The synthetic method of 2 quaternary carbon indoles -3- ketone compounds, it is characterised in that 2- substituted indoles and indoles
The amount ratio of the substance of compound is 1.0：1.0 ~ 10.0, preferably 1.0：2.0~3.0.
The synthetic method of 2 quaternary carbon indoles -3- ketone compounds, it is characterised in that oxidant is peroxide.
The synthetic method of 2 quaternary carbon indoles -3- ketone compounds, it is characterised in that peroxide is selected from 70%
Any one in the tertiary butyl ether of tert-Butanol peroxide aqueous solution, metachloroperbenzoic acid, peroxide, hydrogen peroxide or Peracetic Acid, it is excellent
It is selected as 70% tert-Butanol peroxide aqueous solution.
The synthetic method of 2 quaternary carbon indoles -3- ketone compounds, it is characterised in that the molar equivalent of peroxide
It is 1 ~ 10, preferably molar equivalent is 5.
The reaction route of the present invention is as follows：
After the present invention is by using said synthesis route, synthetic route has following advantage than before：It can be in neutrallty condition
Benzazole compounds are directly converted into 2 quaternary carbon indoles -3- ketone down.And the wider scope of application there are one indole substrates,
Easy to operate, reaction yield is high.
Specific embodiment
Illustrate the synthetic schemes of the present invention with specific embodiment below, but the scope of the present invention is not limited thereto：
Embodiment 1 synthesizes 2- using indoles and 2-phenylindone as substrate（1HIndol-3-yl）2-phenylindone -3- ketone
At room temperature TBHP is added in into 25 mL reaction tubes（70% aq, 0.4 mL）, water（1 mL）, 2-phenylindone（97 mg,
0.5 mmol）And indoles（117 mg, 1 mmol）, 100 DEG C are reacted 24 hours.TLC shows raw material after the reaction was complete, by reaction solution
It is cooled to room temperature, adds in 10 mL saturated sodium bicarbonate aqueous solutions and reaction is quenched.It is extracted with 20 mL ethyl acetate, is associated with later
Machine layer is simultaneously dried with anhydrous sodium sulfate.Post separation is crossed after organic layer concentration（N-hexane：Ethyl acetate=6：1）Obtain yellow powder
Last shape solid 2-（1HIndol-3-yl）146 mg of 2-phenylindone -3- ketone, yield 91%.Fusing point：214-216℃（Point
Solution）；IR (KBr): ν= 3423, 3303, 2924, 1687, 1660, 1616, 1492, 1332, 1278, 1152,
1115, 1053, 889, 746, 688 cm-1；1H NMR (600 MHz, DMSO-d 6) δ 11.08 (bs, 1H),
8.34 (bs, 1H), 7.55-7.43 (m, 4H), 7.39 (d, J = 8.2 Hz, 1H), 7.35-7.25 (m,
3H), 7.10 (d, J = 8.0 Hz, 1H), 7.08-7.03 (m, 2H), 6.99 (d, J = 8.3 Hz, 1H),
6.88-6.82 (m, 1H), 6.74 (t, J = 7.4 Hz, 1H); 13C NMR (150 MHz, DMSO-d 6) δ
200.3, 160.9, 140.0, 137.7, 136.9, 128.1, 127.4, 126.6, 125.5, 124.6, 124.1,
121.3, 120.0, 118.6, 117.5, 117.4, 114.5, 111.9, 111.7, 70.6 ppm; HRMS (ESI)
m/z: calcd. for C22H16N2ONa [M+Na]+ 347.1165, found 347.1155.
Embodiment 2 synthesizes 2- using indoles and 2-phenylindone as substrate（1HIndol-3-yl）2-phenylindone -3- ketone
At room temperature TBHP is added in into 25 mL reaction tubes（70% aq, 0.08 mL）, water（1 mL）, 2-phenylindone（97 mg,
0.5 mmol）And indoles（117 mg, 0.5 mmol）, 100 DEG C are reacted 24 hours.TLC shows that raw material after the reaction was complete, will react
Liquid is cooled to room temperature, and adds in 10 mL saturated sodium bicarbonate aqueous solutions and reaction is quenched.It is extracted with 20 mL ethyl acetate, merged later
Organic layer is simultaneously dried with anhydrous sodium sulfate.Post separation is crossed after organic layer concentration（N-hexane：Ethyl acetate=6：1）Obtain yellow
Pulverulent solids 2-（1HIndol-3-yl）48 mg of 2-phenylindone -3- ketone, yield 30%.
Embodiment 3 synthesizes 2- using indoles and 2-phenylindone as substrate（1HIndol-3-yl）2-phenylindone -3- ketone
At room temperature TBHP is added in into 25 mL reaction tubes（70% aq, 0.8 mL）, water（1 mL）, 2-phenylindone（97 mg,
0.5 mmol）And indoles（117 mg, 1 mmol）, 120 DEG C are reacted 5 hours.TLC shows raw material after the reaction was complete, by reaction solution
It is cooled to room temperature, adds in 10 mL saturated sodium bicarbonate aqueous solutions and reaction is quenched.It is extracted with 20 mL ethyl acetate, is associated with later
Machine layer is simultaneously dried with anhydrous sodium sulfate.Post separation is crossed after organic layer concentration（N-hexane：Ethyl acetate=6：1）Obtain yellow powder
Last shape solid 2-（1HIndol-3-yl）64 mg of 2-phenylindone -3- ketone, yield 40%.
Embodiment 4 synthesizes 2- using indoles and 2-phenylindone as substrate（1HIndol-3-yl）2-phenylindone -3- ketone
At room temperature TBHP is added in into 25 mL reaction tubes（70% aq, 0.4 mL）, water（1 mL）, 2-phenylindone（97 mg,
0.5 mmol）And indoles（585 mg, 5 mmol）, 60 DEG C are reacted 48 hours.TLC shows raw material after the reaction was complete, by reaction solution
It is cooled to room temperature, adds in 10 mL saturated sodium bicarbonate aqueous solutions and reaction is quenched.It is extracted with 20 mL ethyl acetate, is associated with later
Machine layer is simultaneously dried with anhydrous sodium sulfate.Post separation is crossed after organic layer concentration（N-hexane：Ethyl acetate=6：1）Obtain yellow powder
Last shape solid 2-（1HIndol-3-yl）99 mg of 2-phenylindone -3- ketone, yield 62%.
Embodiment 5 synthesizes 2- using indoles and 2-phenylindone as substrate（1HIndol-3-yl）2-phenylindone -3- ketone
At room temperature TBHP is added in into 25 mL reaction tubes（70% aq, 0.4 mL）, water（2.0 mL）, Isosorbide-5-Nitrae-dioxane（0.4
ml）, 2-phenylindone（97 mg, 0.5 mmol）And indoles（117 mg, 1 mmol）, 80 DEG C are reacted 24 hours.TLC displays are former
After expecting that the reaction was complete, reaction solution is cooled to room temperature, 10 mL saturated sodium bicarbonate aqueous solutions is added in and reaction is quenched.With 20 mL second
Acetoacetic ester extracts, and merges organic layer later and is dried with anhydrous sodium sulfate.Post separation is crossed after organic layer concentration（N-hexane：Acetic acid
Ethyl ester=6：1）Obtain yellow powdery solid 2-（1HIndol-3-yl）90 mg of 2-phenylindone -3- ketone, yield 56%.
Embodiment 6 synthesizes 2- using indoles and 2-phenylindone as substrate（1HIndol-3-yl）2-phenylindone -3- ketone
At room temperature TBHP is added in into 25 mL reaction tubes（70% aq, 0.4 mL）, acetonitrile（1 mL）, 2-phenylindone（97 mg,
0.5 mmol）And indoles（117 mg, 1 mmol）, 80 DEG C are reacted 24 hours.TLC shows raw material after the reaction was complete, by reaction solution
It is cooled to room temperature, adds in 10 mL saturated sodium bicarbonate aqueous solutions and reaction is quenched.It is extracted with 20 mL ethyl acetate, is associated with later
Machine layer is simultaneously dried with anhydrous sodium sulfate.Post separation is crossed after organic layer concentration（N-hexane：Ethyl acetate=6：1）Obtain yellow powder
Last shape solid 2-（1HIndol-3-yl）37 mg of 2-phenylindone -3- ketone, yield 23%.
Embodiment 7 synthesizes 2- using indoles and 2-phenylindone as substrate（1HIndol-3-yl）2-phenylindone -3- ketone
At room temperature metachloroperbenzoic acid is added in into 25 mL reaction tubes（430mg, 2.5mmol）, water（1 mL）, 2- phenyl Yin
Diindyl（97 mg, 0.5 mmol）And indoles（117 mg, 1 mmol）, 100 DEG C are reacted 20 hours.TLC shows raw material, and the reaction was complete
Afterwards, reaction solution is cooled to room temperature, adds in 10 mL saturated sodium bicarbonate aqueous solutions and reaction is quenched.Extracted with 20 mL ethyl acetate
It takes, merge organic layer later and is dried with anhydrous sodium sulfate.Post separation is crossed after organic layer concentration（N-hexane：Ethyl acetate=6：
1）Obtain yellow powdery solid 2-（1HIndol-3-yl）32 mg of 2-phenylindone -3- ketone, yield 20%.
Embodiment 8 synthesizes 2- using indoles and 2-phenylindone as substrate（1HIndol-3-yl）2-phenylindone -3- ketone
The tertiary butyl ether of peroxide is added in into 25 mL reaction tubes at room temperature（365mg, 2.5mmol）, toluene（1 mL）, 2-phenylindone
（97 mg, 0.5 mmol）And indoles（117 mg, 1 mmol）, 110 DEG C are reacted 30 hours.TLC shows raw material after the reaction was complete,
Reaction solution is cooled to room temperature, 10 mL saturated sodium bicarbonate aqueous solutions is added in and reaction is quenched.It is extracted with 20 mL ethyl acetate, it
Merge organic layer afterwards and dried with anhydrous sodium sulfate.Post separation is crossed after organic layer concentration（N-hexane：Ethyl acetate=6：1）
To yellow powdery solid 2-（1HIndol-3-yl）39 mg of 2-phenylindone -3- ketone, yield 24%.
Embodiment 9 synthesizes 2- using indoles and 2-phenylindone as substrate（1HIndol-3-yl）2-phenylindone -3- ketone
At room temperature hydrogen peroxide is added in into 25 mL reaction tubes（30% aq, 0.26 mL）, Isosorbide-5-Nitrae-dioxane（1 mL）, 2- benzene
Base indoles（97 mg, 0.5 mmol）And indoles（117 mg, 1 mmol）, 100 DEG C are reacted 18 hours.TLC shows raw material reaction
After completely, reaction solution is cooled to room temperature, 10 mL saturated sodium bicarbonate aqueous solutions is added in and reaction is quenched.With 20 mL ethyl acetate
Extraction merges organic layer and is dried with anhydrous sodium sulfate later.Post separation is crossed after organic layer concentration（N-hexane：Ethyl acetate=
6：1）Obtain yellow powdery solid 2-（1HIndol-3-yl）56 mg of 2-phenylindone -3- ketone, yield 35%.
Embodiment 10 synthesizes 2- using 2-phenylindone and 4- fluoro indoles as substrate（1HThe fluoro- 3- bases of indoles -4-）- 2- benzene
Base indoles -3- ketone
0.4 mL TBHP (70% aq) are added in into 25 mL reaction tubes at room temperature, 1 mL water is added, stirs and evenly mixs.Afterwards will
Reaction tube is placed in 100 DEG C of oil baths, then weighs 2-phenylindone successively（97 mg, 0.5 mmol）With 4- fluoro indoles（135 mg, 1
mmol）It is added in reaction tube, and plus built-in condenser pipe, in 100oIt is reacted 24 hours in C oil baths.TLC shows raw material reaction
After completely, reaction solution is cooled to room temperature, 10 mL saturated sodium bicarbonate aqueous solutions is added in and reaction is quenched.With 20 mL ethyl acetate
Extraction merges organic layer and is dried with anhydrous sodium sulfate later.Post separation is crossed after organic layer concentration（N-hexane：Ethyl acetate=
6：1）Obtain yellow powdery solid 2-（1HThe fluoro- 3- bases of indoles -4-）127 mg of 2-phenylindone -3- ketone, yield 74%.
Fusing point：223-225℃（It decomposes）；IR (KBr): ν = 3446, 3056, 2362, 1686, 1634, 1619, 1486,
1326, 1222, 1145, 996, 847, 738, 700 cm-1; 1H NMR (600 MHz, DMSO-d 6) δ 11.43
(bs, 1H), 7.91 (bs, 1H), 7.49 (t, J = 7.5 Hz, 2H), 7.39 (d, J = 7.6 Hz, 2H),
7.30-7.25 (m, 3H), 7.23 (t, J = 7.2 Hz, 1H), 7.13-7.04 (m, 3H), 6.75 (t, J =
7.4 Hz, 1H), 6.66 (dd, J = 10.9, 7.9 Hz, 1H); 13C NMR (150 MHz, DMSO-d 6) δ
199.7, 160.9, 155.37 (d, J = 245.7 Hz), 140.6, 139.94 (d, J = 11.6 Hz) ,
137.5, 128.0, 127.1, 126.2, 124.8, 124.6, 122.29 (d, J = 7.5 Hz), 117.6,
117.4 , 114.24 (d, J = 20.8 Hz), 112.6, 112.54 (d, J = 3.4 Hz), 108.21 (d, J
= 3.4 Hz), 104.05 (d, J = 19.5 Hz), 70.5 ppm; HRMS (ESI) m/z: calcd. for
C22H16FN2O [M+H]+ 343.1241, found 343.1234。
Embodiment 11 synthesizes 2- using 2-phenylindone and 4- benzyloxy indoles as substrate（1HIndoles -4- benzyloxies -3-
Base）2-phenylindone -3- ketone
0.4 mL TBHP (70% aq) are added in into 25 mL reaction tubes at room temperature, 1 mL water is added, stirs and evenly mixs.Afterwards will
Reaction tube is placed in 100oIn C oil baths, then 2-phenylindone is weighed successively（97 mg, 0.5 mmol）With 4- benzyloxy indoles（223
Mg, 1 mmol）It is added in reaction tube, and plus built-in condenser pipe, is reacted 24 hours in 100 DEG C of oil baths.TLC shows raw material
After the reaction was complete, reaction solution is cooled to room temperature, 10 mL saturated sodium bicarbonate aqueous solutions is added in and reaction is quenched.With 20 mL acetic acid
Ethyl ester extracts, and merges organic layer later and is dried with anhydrous sodium sulfate.Post separation is crossed after organic layer concentration（N-hexane：Acetic acid second
Ester=6：1）Obtain yellow powdery solid 2-（1HIndoles -4- benzyloxy -3- bases）121 mg of 2-phenylindone -3- ketone is received
Rate is 56%.Fusing point：206-208℃（It decomposes）；IR (KBr): ν = 3416, 3313, 3050, 2923, 1678,
1619, 1493, 1462, 1357, 1328, 1237, 1151, 1103, 1070, 915, 782, 756, 740, 696
cm-1; 1H NMR (600 MHz, DMSO-d 6) δ 11.12 (bs, 1H), 7.52-7.41 (m, 3H), 7.29 (dd,J = 4.8, 1.6 Hz, 3H), 7.19-7.10 (m, 5H), 7.08 (dd, J = 6.5, 2.7 Hz, 2H), 7.06
(d, J = 2.5 Hz, 1H), 7.03-6.96 (m, 2H), 6.94 (t, J = 7.9 Hz, 1H), 6.70 (t, J
= 7.4 Hz, 1H), 6.40 (d, J = 7.6 Hz, 1H), 5.05 (d, J = 12.1 Hz, 1H), 4.85 (d,J = 12.1 Hz, 1H); 13C NMR (150 MHz, DMSO-d 6) δ 199.2, 160.0, 151.3, 141.2,
138.9, 137.3, 136.8, 128.1, 128.0, 127.8, 127.6, 126.6, 126.2, 124.6, 123.0,
122.4, 117.5, 117.3, 115.9, 112.9, 112.0, 105.0, 100.5, 70.7, 68.8 ppm; HRMS
(ESI) m/z: calcd. for C29H23N2O2 [M+H]+ 431.1754, found: 431.1745。
Embodiment 12 synthesizes 2- using 2-phenylindone and 5- methyl indols as substrate（1HIndoles -5- methyl -3- bases）-
2-phenylindone -3- ketone
0.4 mL TBHP (70% aq) are added in into 25 mL reaction tubes at room temperature, 1 mL water is added, stirs and evenly mixs.Afterwards will
Reaction tube is placed in 100oIn C oil baths, then 2-phenylindone is weighed successively（97 mg, 0.5 mmol）With 5- methyl indols（131
Mg, 1 mmol）It is added in reaction tube, and plus built-in condenser pipe, is reacted 24 hours in 100 DEG C of oil baths.TLC shows raw material
After the reaction was complete, reaction solution is cooled to room temperature, 10 mL saturated sodium bicarbonate aqueous solutions is added in and reaction is quenched.With 20 mL acetic acid
Ethyl ester extracts, and merges organic layer later and is dried with anhydrous sodium sulfate.Post separation is crossed after organic layer concentration（N-hexane：Acetic acid second
Ester=6：1）Obtain yellow powdery solid 2-（1HIndoles -5- methyl -3- bases）118 mg of 2-phenylindone -3- ketone, yield
It is 70%.Fusing point：197-198℃（It decomposes）；IR (KBr): ν = 3378, 3328, 2920, 1690, 1615, 1486,
1325, 1150, 1113, 1051, 889, 796, 753, 703 cm-1; 1H NMR (600 MHz, DMSO-d 6) δ
10.94 (bs, 1H), 8.28 (bs, 1H), 7.53-7.49 (m, 1H), 7.47 (d, J = 7.7 Hz, 1H),
7.45-7.40 (m, 2H), 7.35-7.23 (m, 4H), 7.02 (d, J = 2.6 Hz, 1H), 6.98 (d, J =
8.3 Hz, 1H), 6.92-6.84 (m, 2H), 6.76-6.72 (m, 1H), 2.21 (s, 3H); 13C NMR (150
MHz, DMSO-d 6) δ 200.2, 160.9, 140.1, 137.6, 135.3, 128.1, 127.3, 126.9,
126.5, 125.7, 124.6, 124.0, 122.9, 119.5, 117.4, 117.3, 113.7, 112.0, 111.4,
70.7, 21.4 ppm; HRMS (ESI) m/z: calcd. for C23H19N2O [M+H]+ 339.1492, found:
339.1498。
Embodiment 13 synthesizes 2- using 2-phenylindone and 7- bromo indoles as substrate（1HThe bromo- 3- bases of indoles -7-）- 2- benzene
Base indoles -3- ketone
0.4 mL TBHP (70% aq) are added in into 25 mL reaction tubes at room temperature, 1 mL water is added, stirs and evenly mixs.Afterwards will
Reaction tube is placed in 100 DEG C of oil baths, then weighs 2-phenylindone successively（97 mg, 0.5 mmol）With 7- bromo indoles（196 mg, 1
mmol）It is added in reaction tube, and plus built-in condenser pipe, in 100oIt is reacted 24 hours in C oil baths.TLC shows raw material reaction
After completely, reaction solution is cooled to room temperature, 10 mL saturated sodium bicarbonate aqueous solutions is added in and reaction is quenched.With 20 mL ethyl acetate
Extraction merges organic layer and is dried with anhydrous sodium sulfate later.Post separation is crossed after organic layer concentration（N-hexane：Ethyl acetate=
6：1）Obtain yellow powdery solid 2-（1HThe bromo- 3- bases of indoles -7-）136 mg of 2-phenylindone -3- ketone, yield 67%.
Fusing point：158-159℃（It decomposes）；IR (KBr): ν = 3408, 2923, 2362, 1686, 1616, 1487, 1466,
1323, 1148, 1000, 881, 780, 751, 699 cm-1; 1H NMR (600 MHz, DMSO-d 6) δ 11.34
(bs, 1H), 8.40 (bs, 1H), 7.55-7.50 (m, 1H), 7.48 (d, J = 7.7 Hz, 1H), 7.45-
7.38 (m, 2H), 7.36-7.25 (m, 4H), 7.13-7.06 (m, 2H), 6.98 (d, J = 8.3 Hz, 1H),
6.83 (t, J = 7.8 Hz, 1H), 6.75 (t, J = 7.4 Hz, 1H); 13C NMR (151 MHz, DMSO) δ
200.0, 160.9, 139.7, 137.9, 135.1, 128.2, 127.5, 127.2, 126.5, 125.2, 124.7,
124.0, 120.2, 119.6, 117.7, 117.2, 115.9, 111.9, 104.4, 70.5 ppm; HRMS (ESI)m/z: calcd. For C22H16BrN2O [M+H]+ 403.0441, found 403.0429。
Embodiment 14 synthesizes 2- using 2-phenylindone and 7- azaindoles as substrate（1HIndoles -7- azepine -3- bases）-
2-phenylindone -3- ketone
0.4 mL TBHP (70% aq) are added in into 25 mL reaction tubes at room temperature, 1 mL water is added, stirs and evenly mixs.Afterwards will
Reaction tube is placed in 100 DEG C of oil baths, then weighs 2-phenylindone successively（97 mg, 0.5 mmol）With 7- azaindoles（118
Mg, 1 mmol）It is added in reaction tube, and plus built-in condenser pipe, is reacted 24 hours in 100 DEG C of oil baths.TLC shows raw material
After the reaction was complete, reaction solution is cooled to room temperature, 10 mL saturated sodium bicarbonate aqueous solutions is added in and reaction is quenched.With 20 mL acetic acid
Ethyl ester extracts, and merges organic layer later and is dried with anhydrous sodium sulfate.Post separation is crossed after organic layer concentration（N-hexane：Acetic acid second
Ester=6：1）Obtain yellow powdery solid 2-（1HIndoles -7- azepine -3- bases）46 mg of 2-phenylindone -3- ketone, yield
It is 28%.Fusing point：234-236℃（It decomposes）；IR (KBr): ν = 3325, 3135, 3032, 2923, 1682, 1667,
1618, 1489, 1465, 1419, 1325, 1288, 1147, 1122, 1034, 887, 799, 749, 701 cm-1;1H NMR (600 MHz, DMSO-d 6) δ 11.64 (bs, 1H), 8.41 (bs, 1H), 8.18 (d, J = 3.7
Hz, 1H), 7.55-7.50 (m, 1H), 7.50-7.45 (m, 2H), 7.41 (d, J = 7.2 Hz, 2H), 7.31
(dt, J = 23.0, 7.1 Hz, 3H), 7.20 (d, J = 2.6 Hz, 1H), 6.98 (d, J = 8.3 Hz,
1H), 6.94 (dd, J = 7.9, 4.7 Hz, 1H), 6.75 (t, J = 7.4 Hz, 1H); 13C NMR (150
MHz, DMSO-d 6) δ 200.1, 160.9, 148.9, 142.9, 139.8, 138.0, 128.3, 128.3,
127.6, 126.6, 124.7, 124.2, 117.8, 117.7, 117.2, 115.3, 113.4, 111.9, 70.5
ppm; HRMS (ESI) m/z: calcd. for C21H16N3O[M+H]+ 326.1288, found: 326.1296。
Embodiment 15 synthesizes 2- using 2- ethylindoles and indoles as substrate（1HIndoles -7- azepine -3- bases）- 2- ethyls
Indoles -3- ketone
0.4 mL TBHP (70% aq) are added in into 25 mL reaction tubes at room temperature, 1 mL water is added, stirs and evenly mixs.Afterwards will
Reaction tube is placed in 100 DEG C of oil baths, then weighs 2- ethylindoles successively（73 mg, 0.5 mmol）And indoles（117 mg, 1
mmol）It is added in reaction tube, and plus built-in condenser pipe, is reacted 24 hours in 100 DEG C of oil baths.TLC shows raw material reaction
After completely, reaction solution is cooled to room temperature, 10 mL saturated sodium bicarbonate aqueous solutions is added in and reaction is quenched.With 20 mL ethyl acetate
Extraction merges organic layer and is dried with anhydrous sodium sulfate later.Post separation is crossed after organic layer concentration（N-hexane：Ethyl acetate=
6：1）Obtain yellow powdery solid 2-（1HIndol-3-yl）124 mg of -2- ethylindole -3- ketone, yield 90%.Fusing point：
234-236℃（It decomposes）；1H NMR (600 MHz, DMSO-d 6) δ 11.02 (bs, 1H), 7.77 (bs, 1H),
7.50-7.46 (m, 1H), 7.42 (dd, J = 16.0, 7.9 Hz, 2H), 7.38-7.30 (m, 2H), 7.03
(t, J = 7.5 Hz, 1H), 6.96 (d, J = 8.3 Hz, 1H), 6.87 (t, J = 7.5 Hz, 1H), 6.69
(t, J = 7.3 Hz, 1H), 2.21 (dq, J = 14.6, 7.3 Hz, 1H), 2.10 (dq, J = 14.2, 7.1
Hz, 1H), 0.79 (t, J = 7.3 Hz, 3H); 13C NMR (150 MHz, DMSO-d 6) δ 202.8, 161.4,
137.4, 136.8, 125.0, 124.0, 123.2, 121.1, 120.2, 118.9, 118.5, 116.9, 113.6,
111.7, 111.6, 69.2, 29.4, 8.1 ppm; IR (KBr): ν = 3360, 2972, 2934, 1664,
1613, 1488, 1459, 1325, 1246,1153, 1132, 1098, 1048, 1001, 881, 780, 747, 714
cm-1; HRMS (ESI) m/z: calcd. For C18H17BN2O [M+H]+ 277.1335, found 277.1340。
Embodiment 16 synthesizes 2- using 2- rubigan indoles and 5- cyanoindoles as substrate（1HIndoles -5- cyanogen -3-
Base）- 2- rubigan indoles -3- ketone
0.4 mL TBHP (70% aq) are added in into 25 mL reaction tubes at room temperature, 1 mL water is added, stirs and evenly mixs.Afterwards will
Reaction tube is placed in 100 DEG C of oil baths, then weighs 2- rubigan indoles successively（114 mg, 0.5 mmol）With 5- cyanoindoles
（142 mg, 1 mmol）It is added in reaction tube, and plus built-in condenser pipe, is reacted 24 hours in 100 DEG C of oil baths.TLC is shown
After showing raw material the reaction was complete, reaction solution is cooled to room temperature, 10 mL saturated sodium bicarbonate aqueous solutions is added in and reaction is quenched.With 20
ML ethyl acetate extracts, and merges organic layer later and is dried with anhydrous sodium sulfate.Post separation is crossed after organic layer concentration（N-hexane：
Ethyl acetate=6：1）Obtain yellow powdery solid 2-（1HIndoles -5- cyano -3- bases）- 2- rubigan indoles -3- ketone
55 mg, yield 72%.Fusing point：143-145℃（It decomposes）；IR (KBr): ν = 3414, 2923, 2426, 2221,
1683, 1617, 1488, 1467, 1385, 1351, 1326, 1146, 1014, 891, 754, 669 cm-1; 1H
NMR (600 MHz, DMSO-d 6) δ 11.75 (bs, 1H), 8.55 (bs, 1H), 7.60-7.53 (m, 3H),
7.51 (d, J = 7.7 Hz, 1H), 7.44 (dd, J = 8.4, 1.3 Hz, 1H), 7.43-7.36 (m, 5H),
7.00 (d, J = 8.3 Hz, 1H), 6.78 (t, J = 7.4 Hz, 1H); 13C NMR (150 MHz, DMSO-d 6)
δ 199.4, 160.9, 138.8, 138.6, 138.2, 132.5, 128.4, 128.3, 126.7, 125.4,
125.1, 124.8, 124.2, 120.5, 118.1, 116.9, 114.8, 113.3, 112.0, 100.9, 69.7
ppm; HRMS (ESI) m/z: calcd. for C23H15ClN3O [M+H]+ 384.0898, found: 384.0890。
Embodiment 17 with 2- phenyl-NMethyl indol and indoles synthesize 2- for substrate（1HIndoles-3-base）- 2- benzene
Base-NMethyl indol -3- ketone
0.4 mL TBHP (70% aq) are added in into 25 mL reaction tubes at room temperature, 1 mL water is added, stirs and evenly mixs.Afterwards will
Reaction tube is placed in 100 DEG C of oil baths, then weigh successively 2- phenyl-NMethyl indol（104 mg, 0.5 mmol）And indoles（117
Mg, 1 mmol）It is added in reaction tube, and plus built-in condenser pipe, is reacted 24 hours in 100 DEG C of oil baths.TLC shows raw material
After the reaction was complete, reaction solution is cooled to room temperature, 10 mL saturated sodium bicarbonate aqueous solutions is added in and reaction is quenched.With 20 mL acetic acid
Ethyl ester extracts, and merges organic layer later and is dried with anhydrous sodium sulfate.Post separation is crossed after organic layer concentration（N-hexane：Acetic acid second
Ester=6：1）Obtain yellow powdery solid 2-（1HIndol-3-yl）- 2- phenyl-N86 mg of methyl indol -3- ketone, yield
It is 50%.Fusing point：216-220℃（It decomposes）；1H NMR (600 MHz, DMSO-d 6) δ 11.24 (bs, 1H), 7.65-
7.58 (m, 1H), 7.50 (d, J = 7.5 Hz, 1H), 7.42-7.35 (m, 6H), 7.08 (d, J = 2.5
Hz, 1H), 7.07-7.04 (m, 2H), 6.81 (t, J = 7.5 Hz, 1H), 6.79-6.75 (m, 2H), 2.83
(s, 3H); 13C NMR (150 MHz, DMSO-d 6) δ 199.9, 160.1, 138.3, 137.5, 136.7,
128.5, 127.9, 127.3, 126.5, 125.5, 124.6, 121.3, 119.8, 119.0, 117.6, 117.1,
112.0, 111.7, 108.8, 75.6, 29.2 ppm; HRMS (ESI) m/z: calcd. for C23H19N2O [M+H
]+ 339.1492, found: 339.1495。
Embodiment 18 with 2-phenylindone and 5- cyano-NMethyl indol synthesizes 2- for substrate（5- cyano -1H-NFirst
Base indol-3-yl）2-phenylindone -3- ketone
0.4 mL TBHP (70% aq) are added in into 25 mL reaction tubes at room temperature, 1 mL water is added, stirs and evenly mixs.Afterwards will
Reaction tube is placed in 100 DEG C of oil baths, then weighs 2-phenylindone successively（97 mg, 0.5 mmol）With 5- cyano-NMethyl indol
（156 mg, 1 mmol）It is added in reaction tube, and plus built-in condenser pipe, is reacted 24 hours in 100 DEG C of oil baths.TLC is shown
After showing raw material the reaction was complete, reaction solution is cooled to room temperature, 10 mL saturated sodium bicarbonate aqueous solutions is added in and reaction is quenched.With 20
ML ethyl acetate extracts, and merges organic layer later and is dried with anhydrous sodium sulfate.Post separation is crossed after organic layer concentration（N-hexane：
Ethyl acetate=6：1）Obtain yellow powdery solid 2-（5- cyano -1H-NMethyl indol -3- bases）2-phenylindone -3-
85 mg of ketone, yield 47%.Fusing point：244-246℃（It decomposes）；IR (KBr): ν = 3450, 2925, 2216, 1695,
1618, 1485, 1468, 1320, 1143, 991, 892, 796, 751, 701 cm-1; 1H NMR (600 MHz,
DMSO-d 6) δ 8.52 (bs, 1H), 7.64 (d, J = 8.5 Hz, 1H), 7.58-7.52 (m, 2H), 7.52-
7.47 (m, 2H), 7.42 (d, J = 2.1 Hz, 1H), 7.39-7.26 (m, 5H), 6.99 (d, J = 8.3
Hz, 1H), 6.77 (t, J = 7.4 Hz, 1H), 3.82 (s, 3H); 13C NMR (150 MHz, DMSO-d 6) δ
199.7, 161.0, 139.5, 139.0, 138.2, 130.8, 128.5, 127.8, 126.4, 125.7, 125.6,
124.8, 124.1, 120.6, 118.0, 117.0, 114.6, 112.0, 111.7, 100.9, 70.2, 32.8
ppm; HRMS (ESI) m/z: calcd. for C24H18N3O[M+H]+ 364.1444, found: 364.1445。
Claims (7)
1. a kind of synthetic method of 2 quaternary carbons indoles -3- ketone compounds, it is characterised in that anti-equipped with oxidant and solvent
It answers and formula is added in bottle（Ⅰ）Shown substrate 2- substituted indoles and formula（Ⅱ）Shown Benzazole compounds, in 60 ~ 140 DEG C of oil baths
1 ~ 48 h of middle reaction, is cooled to room temperature after reaction, adds in saturated sodium bicarbonate and reaction is quenched, then extraction and separation are concentrated to give
Formula（Ⅲ）Shown 2 quaternary carbon indoles -3- ketone compounds of product,
,
In formula, R1、R3For hydrogen atom or alkyl, R2For hydrogen atom, alkyl, aryl, R4For hydrogen atom, alkyl, halogen, aryl, benzyl
Oxygroup, nitro or cyano.
2. the synthetic method of 2 quaternary carbons indoles -3- ketone compounds according to claim 1, it is characterised in that solvent selects
From the mixture of one or more of Isosorbide-5-Nitrae-dioxane, acetonitrile, toluene, water arbitrary proportion, preferably water.
3. the synthetic method of 2 quaternary carbons indoles -3- ketone compounds according to claim 1, it is characterised in that reaction temperature
It is 60-120 DEG C to spend, preferably 100 DEG C, and the reaction time is 5-48 hours, preferably 24 hours.
4. the synthetic method of 2 quaternary carbons indoles -3- ketone compounds according to claim 1, it is characterised in that 2- replaces
The amount ratio of the substance of indoles and Benzazole compounds is 1.0：1.0 ~ 10.0, preferably 1.0：2.0~3.0.
5. the synthetic method of 2 quaternary carbons indoles -3- ketone compounds according to claim 1, it is characterised in that oxidant
For peroxide.
6. the synthetic method of 2 quaternary carbons indoles -3- ketone compounds according to claim 5, it is characterised in that peroxidating
Object is in 70% tert-Butanol peroxide aqueous solution, metachloroperbenzoic acid, the tertiary butyl ether of peroxide, hydrogen peroxide or Peracetic Acid
Any one, preferably 70% tert-Butanol peroxide aqueous solution.
7. the synthetic method of 2 quaternary carbons indoles -3- ketone compounds according to claim 1, it is characterised in that peroxidating
The molar equivalent of object is 1 ~ 10, and preferably molar equivalent is 5.
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