CN106117216A - A kind of method of atmospheric high efficiency synthesis 6H iso-indoles [2,1 a] indole 6 ketone compounds - Google Patents
A kind of method of atmospheric high efficiency synthesis 6H iso-indoles [2,1 a] indole 6 ketone compounds Download PDFInfo
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- CN106117216A CN106117216A CN201610735716.5A CN201610735716A CN106117216A CN 106117216 A CN106117216 A CN 106117216A CN 201610735716 A CN201610735716 A CN 201610735716A CN 106117216 A CN106117216 A CN 106117216A
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- 0 C*=C(c(c(-c1c2)c3)ccc3Cl)[n]1c1c2c(C)ccc1 Chemical compound C*=C(c(c(-c1c2)c3)ccc3Cl)[n]1c1c2c(C)ccc1 0.000 description 1
- SPRPVSPVTYSFDS-UHFFFAOYSA-N CCc(cc1-c2cc3c(C)cccc3[n-]2)ccc1Br Chemical compound CCc(cc1-c2cc3c(C)cccc3[n-]2)ccc1Br SPRPVSPVTYSFDS-UHFFFAOYSA-N 0.000 description 1
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
Abstract
The invention discloses a kind of atmospheric high efficiency synthesis 6HIso-indoles [2,1a] method of indole 6 ketone compounds.Technical scheme main points are: with 2 (2 bromine aryl) 1HBenzazole compounds and CO are initiation material, under the effect of transition metal palladium catalyst, part and alkali, prepare target product 6 in 100 140 DEG C of heated and stirred reactions in organic solventHIso-indoles [2,1a] indole 6 ketone compounds.The present invention has that reaction condition is gentle, initiation material is the most easily prepared, wide application range of substrates and simple operation and other advantages.
Description
Technical field
The invention belongs to technical field of organic synthesis, be specifically related to a kind of atmospheric high efficiency synthesis 6H-iso-indoles [2,1-a] Yin
The method of diindyl-6-ketone compounds.
Background technology
Iso-indoles diindyl ketone compounds is widely present in natural alkaloid and bioactive molecule, attracts in recent years
Increasing organic chemist and the extensive concern of medicine scholar and research.Wherein, 6H-iso-indoles [2,1-a] indole-6-
Ketone compounds not only has potential anti-tumor activity, but also is used successfully as the part of melatonin MT3 and Hnk1.
In document, 6H-iso-indoles [2,1-a] indole-6-ketone compounds is mostly the molecule of the N-benzoyl indole by palladium chtalyst
Cascade reaction, the isonitrile of palladium chtalyst or the high pressure CO (20atm) that internal oxidition coupling reaction, phosphorus ylide participate in and 2-(2-bromine virtue
Base) insertion reaction of-1H-indole and prepared.These methods have synthetic route loaded down with trivial details, operation complexity, severe reaction conditions,
Use the higher reagent of toxicity or the shortcoming such as productivity is relatively low, which greatly limits the range of application of such synthetic method.
In view of importance and the deficiency of existing synthetic method of 6H-iso-indoles [2,1-a] indole-6-ketone compounds, develop simple and direct,
The synthetic method of this compounds efficient is the most necessary.
Summary of the invention
Present invention solves the technical problem that and there is provided that a kind of reaction condition is gentle, initiation material is the most easily prepared, substrate
The method of atmospheric high efficiency synthesis 6H-iso-indoles [2,1-a] indole-6-ketone compounds applied widely and simple to operate.
The present invention solves that above-mentioned technical problem adopts the following technical scheme that, a kind of atmospheric high efficiency synthesis 6H-iso-indoles [2,
1-a] method of indole-6-ketone compounds, it is characterised in that: with 2-(2-bromine aryl)-1H-Benzazole compounds and CO for rising
Beginning raw material, under the effect of transition metal palladium catalyst, part and alkali, anti-in 100-140 DEG C of heated and stirred in organic solvent
Should prepare target product 6H-iso-indoles [2,1-a] indole-6-ketone compounds, the reaction equation in this synthetic method is:
Described transition metal palladium catalyst is PdCl2、Pd(PPh3)2Cl2、Pd2(dba)3Or Pd (OAc)2, part is
BuPAd2, X-Phos or [(t-Bu)3PH]BF4, alkali is DABCO or Et3N, organic solvent is dimethyl sulfoxide, N, N-dimethyl
Methanamide or N-Methyl pyrrolidone.R in reaction equation1For hydrogen, methyl or chlorine, R2For hydrogen, methyl, methoxyl group, fluorine or chlorine.
Atmospheric high efficiency of the present invention synthesizes the concrete of the method for 6H-iso-indoles [2,1-a] indole-6-ketone compounds
Step is: under the CO atmosphere of 1atm, successively by 2-(2-bromine aryl)-1H-Benzazole compounds, the catalysis of transition metal palladium salt
Agent, part, alkali and organic solvent are added in Schlenk reaction tube, are then reacted in 100-140 DEG C of heated and stirred by this mixture
12h, after having reacted, adds saturated ammonium chloride solution cancellation reaction in reaction tube, and dichloromethane extracts, and organic facies is used successively
Deionized water and saturated nacl aqueous solution washing, anhydrous sodium sulfate is dried, and filters, is spin-dried for, silica gel column chromatography isolated target
Product 6H-iso-indoles [2,1-a] indole-6-ketone compounds.
2-of the present invention (2-bromine aryl)-1H-Benzazole compounds, transition metal palladium catalyst, part and alkali
Molar ratio is 1:0.05-0.1:0.15-0.3:3.
Instant invention overcomes at present that synthetic route is loaded down with trivial details, operation is complicated, reaction condition is severe in such compou nd synthesis method
Carve and use the shortcomings such as expensive reagent, being a kind of atmospheric high efficiency synthesis 6H-iso-indoles [2,1-a] indole-6-ketone compounds
Method, this synthetic method has that reaction condition is gentle, initiation material is the most easily prepared, wide application range of substrates and simple to operate
Etc. advantage.
Detailed description of the invention
By the following examples the foregoing of the present invention is described in further details, but this should be interpreted as this
The scope inventing above-mentioned theme is only limitted to below example, and all technology realized based on foregoing of the present invention belong to this
Bright scope.
Embodiment 1
The schlenk reaction tube of 15mL is sequentially added into indole 1a (0.4mmol, 109mg), palladium (4.5mg,
0.02mmol), normal-butyl two (1-adamantyl) phosphine (BDAP) (21.5mg, 0.06mmol), DABCO (134.6mg,
1.2mmol) with dimethyl sulfoxide (1.5mL), evacuation fills CO (1atm) three times, reacts 12h in 120 DEG C of heated and stirred afterwards.
After having reacted, adding saturated ammonium chloride solution cancellation reaction in reaction tube, dichloromethane extracts, organic facies deionized water
Washing with saturated nacl aqueous solution, anhydrous sodium sulfate is dried.Filter, be spin-dried for, silicagel column separation excessively (petroleum ether/dichloromethane=
3/1) yellow solid 6H-iso-indoles [2,1-a] indole-6-ketone 2a (85mg, 97%), is obtained.The sign data of this compound are as follows
:1H NMR(CDCl3, 400MHz) and δ 6.52 (s, 1H), 7.12 (t, J=7.6Hz, 1H), 7.24-7.30 (m, 2H), 7.39-7.44
(m, 3H), 7.70 (d, J=7.6Hz, 1H), 7.85 (d, J=8.0Hz, 1H)；13C NMR(CDCl3,100MHz)δ103.4,
113.3,121.2,122.3,123.9,125.2,126.3,128.7,133.57,133.63,133.8,134.5,134.6,
138.8,162.5.MS(ESI)m/z 220[M+H]+。
Embodiment 2
Method as described in embodiment 1, be sequentially added in the schlenk reaction tube of 15mL indole 1a (0.4mmol,
109mg)、PdCl2(3.5mg, 0.02mmol), normal-butyl two (1-adamantyl) phosphine (BDAP) (21.5mg, 0.06mmol),
DABCO (134.6mg, 1.2mmol) and dimethyl sulfoxide (1.5mL), evacuation fills CO (1atm) three times, adds in 120 DEG C afterwards
Thermal agitation reaction 12h, obtains product 6H-iso-indoles [2,1-a] indole-6-ketone 2a (18mg, 20%).
Embodiment 3
Method as described in embodiment 1, be sequentially added in the schlenk reaction tube of 15mL indole 1a (0.4mmol,
109mg)、Pd(PPh3)2Cl2(14mg, 0.02mmol), normal-butyl two (1-adamantyl) phosphine (BDAP) (21.5mg,
0.06mmol), DABCO (134.6mg, 1.2mmol) and dimethyl sulfoxide (1.5mL), evacuation fills CO (1atm) three times, afterwards
React 12h in 120 DEG C of heated and stirred, obtain product 6H-iso-indoles [2,1-a] indole-6-ketone 2a (40mg, 46%).Embodiment 4
Method as described in embodiment 1, be sequentially added in the schlenk reaction tube of 15mL indole 1a (0.4mmol,
109mg)、Pd2(dba)3(18mg, 0.02mmol), normal-butyl two (1-adamantyl) phosphine (BDAP) (21.5mg, 0.06mmol),
DABCO (134.6mg, 1.2mmol) and dimethyl sulfoxide (1.5mL), evacuation fills CO (1atm) three times, adds in 120 DEG C afterwards
Thermal agitation reaction 12h, obtains product 6H-iso-indoles [2,1-a] indole-6-ketone 2a (51mg, 58%).
Embodiment 5
Method as described in embodiment 1, be sequentially added in the schlenk reaction tube of 15mL indole 1a (0.4mmol,
109mg), palladium (4.5mg, 0.02mmol), X-Phos (29mg, 0.06mmol), DABCO (134.6mg, 1.2mmol) and
Dimethyl sulfoxide (1.5mL), evacuation fills CO (1atm) three times, reacts 12h in 120 DEG C of heated and stirred afterwards, obtains product 6H-different
Indole [2,1-a] indole-6-ketone 2a (25mg, 29%).
Embodiment 6
Method as described in embodiment 1, be sequentially added in the schlenk reaction tube of 15mL indole 1a (0.4mmol,
109mg), palladium (4.5mg, 0.02mmol), [(t-Bu)3PH]BF4(17mg,0.06mmol)、DABCO(134.6mg,
1.2mmol) with dimethyl sulfoxide (1.5mL), evacuation fills CO (1atm) three times, reacts 12h in 120 DEG C of heated and stirred afterwards,
Obtain product 6H-iso-indoles [2,1-a] indole-6-ketone 2a (28mg, 32%).
Embodiment 7
Method as described in embodiment 1, be sequentially added in the schlenk reaction tube of 15mL indole 1a (0.4mmol,
109mg), palladium (4.5mg, 0.02mmol), TFP (14mg, 0.06mmol), DABCO (134.6mg, 1.2mmol) and diformazan
Base sulfoxide (1.5mL), evacuation fills CO (1atm) three times, reacts 12h in 120 DEG C of heated and stirred afterwards, does not obtains product 6H-different
Indole [2,1-a] indole-6-ketone 2a.
Embodiment 8
Method as described in embodiment 1, be sequentially added in the schlenk reaction tube of 15mL indole 1a (0.4mmol,
109mg), palladium (4.5mg, 0.02mmol), PCy3(17mg, 0.06mmol), DABCO (134.6mg, 1.2mmol) and two
Methyl sulfoxide (1.5mL), evacuation fills CO (1atm) three times, reacts 12h in 120 DEG C of heated and stirred afterwards, does not obtains product 6H-
Iso-indoles [2,1-a] indole-6-ketone 2a.
Embodiment 9
Method as described in embodiment 1, be sequentially added in the schlenk reaction tube of 15mL indole 1a (0.4mmol,
109mg), palladium (4.5mg, 0.02mmol), normal-butyl two (1-adamantyl) phosphine (BDAP) (21.5mg, 0.06mmol),
DBU (182mg, 1.2mmol) and dimethyl sulfoxide (1.5mL), evacuation fills CO (1atm) three times, stirs 120 DEG C of heating afterwards
Mix 12h, do not obtain product 6H-iso-indoles [2,1-a] indole-6-ketone 2a.
Embodiment 10
Method as described in embodiment 1, be sequentially added in the schlenk reaction tube of 15mL indole 1a (0.4mmol,
109mg), palladium (4.5mg, 0.02mmol), normal-butyl two (1-adamantyl) phosphine (BDAP) (21.5mg, 0.06mmol),
(CH3)3COK (134mg, 1.2mmol) and dimethyl sulfoxide (1.5mL), evacuation fills CO (1atm) three times, adds at 120 DEG C afterwards
Thermal agitation 12h, does not obtains product 6H-iso-indoles [2,1-a] indole-6-ketone 2a.
Embodiment 11
Method as described in embodiment 1, be sequentially added in the schlenk reaction tube of 15mL indole 1a (0.4mmol,
109mg), palladium (4.5mg, 0.02mmol), normal-butyl two (1-adamantyl) phosphine (BDAP) (21.5mg, 0.06mmol),
Et3N (121mg, 1.2mmol) and dimethyl sulfoxide (1.5mL), evacuation fills CO (1atm) three times, stirs in 120 DEG C of heating afterwards
Mix reaction 12h, obtain product 6H-iso-indoles [2,1-a] indole-6-ketone 2a (27mg, 31%).
Embodiment 12
Method as described in embodiment 1, be sequentially added in the schlenk reaction tube of 15mL indole 1a (0.4mmol,
109mg), palladium (4.5mg, 0.02mmol), normal-butyl two (1-adamantyl) phosphine (BDAP) (21.5mg, 0.06mmol),
K2CO3(166mg, 1.2mmol) and dimethyl sulfoxide (1.5mL), evacuation fills CO (1atm) three times, stirs in 120 DEG C of heating afterwards
Mix reaction 12h, do not obtain product 6H-iso-indoles [2,1-a] indole-6-ketone 2a.
Embodiment 13
Method as described in embodiment 1, be sequentially added in the schlenk reaction tube of 15mL indole 1a (0.4mmol,
109mg), palladium (4.5mg, 0.02mmol), normal-butyl two (1-adamantyl) phosphine (BDAP) (21.5mg, 0.06mmol),
DABCO (134.6mg, 1.2mmol) and DMF (1.5mL), evacuation fills CO (1atm) three times, afterwards in
120 DEG C of heated and stirred reaction 12h, obtain product 6H-iso-indoles [2,1-a] indole-6-ketone 2a (40mg, 46%).Embodiment 14
Method as described in embodiment 1, be sequentially added in the schlenk reaction tube of 15mL indole 1a (0.4mmol,
109mg), palladium (4.5mg, 0.02mmol), normal-butyl two (1-adamantyl) phosphine (BDAP) (21.5mg, 0.06mmol),
DABCO (134.6mg, 1.2mmol) and N-Methyl pyrrolidone (1.5mL), evacuation fills CO (1atm) three times, afterwards in 120
DEG C heated and stirred reaction 12h, obtains product 6H-iso-indoles [2,1-a] indole-6-ketone 2a (59mg, 67%).
Embodiment 15
Method as described in embodiment 1, be sequentially added in the schlenk reaction tube of 15mL indole 1a (0.4mmol,
109mg), palladium (4.5mg, 0.02mmol), normal-butyl two (1-adamantyl) phosphine (BDAP) (21.5mg, 0.06mmol),
DABCO (134.6mg, 1.2mmol) and dimethyl sulfoxide (1.5mL), evacuation fills CO (1atm) three times, adds in 100 DEG C afterwards
Thermal agitation reaction 12h, obtains product 6H-iso-indoles [2,1-a] indole-6-ketone 2a (31mg, 35%).
Embodiment 16
Method as described in embodiment 1, be sequentially added in the schlenk reaction tube of 15mL indole 1a (0.4mmol,
109mg), palladium (4.5mg, 0.02mmol), normal-butyl two (1-adamantyl) phosphine (BDAP) (21.5mg, 0.06mmol),
DABCO (134.6mg, 1.2mmol) and dimethyl sulfoxide (1.5mL), evacuation fills CO (1atm) three times, adds in 140 DEG C afterwards
Thermal agitation reaction 12h, obtains product 6H-iso-indoles [2,1-a] indole-6-ketone 2a (75mg, 86%).
Embodiment 17
Method as described in embodiment 1, be sequentially added in the schlenk reaction tube of 15mL indole 1b (0.4mmol,
115mg), palladium (4.5mg, 0.02mmol), normal-butyl two (1-adamantyl) phosphine (BDAP) (21.5mg, 0.06mmol),
DABCO (134.6mg, 1.2mmol) and dimethyl sulfoxide (1.5mL), evacuation fills CO (1atm) three times, adds in 120 DEG C afterwards
Thermal agitation reaction 12h.After having reacted, adding saturated ammonium chloride solution cancellation reaction in reaction tube, dichloromethane extracts, has
Machine washs with deionized water and saturated nacl aqueous solution mutually, and anhydrous sodium sulfate is dried.Filter, be spin-dried for, cross silicagel column and separate (oil
Ether/dichloromethane=3/1), obtain yellow solid 3-methyl-6H-iso-indoles [2,1-a] indole-6-ketone 2b (77mg, 82%).Should
The sign data of compound are as follows:1H NMR(CDCl3, 400MHz) and δ 2.48 (s, 3H), 6.64 (s, 1H), 6.96 (d, J=
7.6Hz, 1H), 7.18 (t, J=7.6Hz, 1H), 7.31-7.34 (m, 1H), 7.49-7.50 (m, 2H), 7.71-7.75 (m,
2H)；13C NMR(CDCl3,100MHz)δ18.4,102.0,110.8,121.0,124.5,125.1,126.3,128.6,
131.9,133.3,133.6,133.7,134.0,134.7,138.1,162.6.HRMS(ESI)calcd for C16H12NO[M+
H]+234.0913,found 234.0926。
Embodiment 18
Method as described in embodiment 1, be sequentially added in the schlenk reaction tube of 15mL indole 1c (0.4mmol,
115mg), palladium (4.5mg, 0.02mmol), normal-butyl two (1-adamantyl) phosphine (BDAP) (21.5mg, 0.06mmol),
DABCO (134.6mg, 1.2mmol) and dimethyl sulfoxide (1.5mL), evacuation fills CO (1atm) three times, adds in 120 DEG C afterwards
Thermal agitation reaction 12h.After having reacted, adding saturated ammonium chloride solution cancellation reaction in reaction tube, dichloromethane extracts, has
Machine washs with deionized water and saturated nacl aqueous solution mutually, and anhydrous sodium sulfate is dried.Filter, be spin-dried for, cross silicagel column and separate (oil
Ether/dichloromethane=3/1), obtain yellow solid 1-methyl-6H-iso-indoles [2,1-a] indole-6-ketone 2c (81mg, 87%).Should
The sign data of compound are as follows: 1H NMR (CDCl3, 400MHz) and δ 2.42 (s, 3H), 6.47 (s, 1H), 6.93 (d, J=
8.0Hz,1H),7.25-7.28(m,2H),7.40-7.46(m,2H),7.66-7.70(m,2H)；13C NMR(CDCl3,
100MHz)δ21.8,103.6,113.7,121.0,121.8,125.12,125.15,128.4,132.1,133.5,133.7,
133.9,134.7,136.8,138.1,162.6.HRMS(ESI)calcd for C16H12NO[M+H]+234.0913,found
234.0924。
Embodiment 19
Method as described in embodiment 1, be sequentially added in the schlenk reaction tube of 15mL indole 1d (0.4mmol,
122mg), palladium (4.5mg, 0.02mmol), normal-butyl two (1-adamantyl) phosphine (BDAP) (21.5mg, 0.06mmol),
DABCO (134.6mg, 1.2mmol) and dimethyl sulfoxide (1.5mL), evacuation fills CO (1atm) three times, adds in 120 DEG C afterwards
Thermal agitation reaction 12h.After having reacted, adding saturated ammonium chloride solution cancellation reaction in reaction tube, dichloromethane extracts, has
Machine washs with deionized water and saturated nacl aqueous solution mutually, and anhydrous sodium sulfate is dried.Filter, be spin-dried for, cross silicagel column and separate (oil
Ether/dichloromethane=3/1), obtain yellow solid 2-chloro-6H-iso-indoles [2,1-a] indole-6-ketone 2d (71mg, 70%).This change
The sign data of compound are as follows:1H NMR(CDCl3, 400MHz) and δ 6.50 (s, 1H), 7.21 (d, J=8.0Hz, 1H), 7.33-
7.38 (m, 2H), 7.47-7.53 (m, 2H), 7.74 (t, J=8.8Hz, 2H)；13C NMR(CDCl3,100MHz)δ102.4,
114.0,121.4,121.9,125.4,126.3,129.2,129.4,131.8,133.6,133.9,134.3,135.7,
140.1,162.3.MS(ESI)m/z 254[M+H]+。
Embodiment 20
Method as described in embodiment 1, be sequentially added in the schlenk reaction tube of 15mL indole 1e (0.4mmol,
114mg), palladium (4.5mg, 0.02mmol), normal-butyl two (1-adamantyl) phosphine (BDAP) (21.5mg, 0.06mmol),
DABCO (134.6mg, 1.2mmol) and dimethyl sulfoxide (1.5mL), evacuation fills CO (1atm) three times, adds in 120 DEG C afterwards
Thermal agitation reaction 12h.After having reacted, adding saturated ammonium chloride solution cancellation reaction in reaction tube, dichloromethane extracts, has
Machine washs with deionized water and saturated nacl aqueous solution mutually, and anhydrous sodium sulfate is dried.Filter, be spin-dried for, cross silicagel column and separate (oil
Ether/dichloromethane=3/1), obtain yellow solid 8-methyl-6H-iso-indoles [2,1-a] indole-6-ketone 2e (75mg, 81%).Should
The sign data of compound are as follows:1H NMR(CDCl3, 400MHz) and δ 2.34 (s, 3H), 6.45 (s, 1H), 7.11 (t, J=
7.6Hz, 1H), 7.20-7.26 (m, 2H), 7.30 (d, J=7.6Hz, 1H), 7.38 (d, J=7.6Hz, 1H), 7.47 (s, 1H),
7.83 (d, J=8.0Hz, 1H)；13C NMR(CDCl3,100MHz)δ21.4,102.7,113.2,121.0,122.1,123.7,
125.6,126.0,131.9,133.5,134.0,134.3,134.6,139.0,139.2,162.8.MS(ESI)m/z 234[M+
H]+。
Embodiment 21
Method as described in embodiment 1, be sequentially added in the schlenk reaction tube of 15mL indole 1f (0.4mmol,
121mg), palladium (4.5mg, 0.02mmol), normal-butyl two (1-adamantyl) phosphine (BDAP) (21.5mg, 0.06mmol),
DABCO (134.6mg, 1.2mmol) and dimethyl sulfoxide (1.5mL), evacuation fills CO (1atm) three times, adds in 120 DEG C afterwards
Thermal agitation reaction 12h.After having reacted, adding saturated ammonium chloride solution cancellation reaction in reaction tube, dichloromethane extracts, has
Machine washs with deionized water and saturated nacl aqueous solution mutually, and anhydrous sodium sulfate is dried.Filter, be spin-dried for, cross silicagel column and separate (oil
Ether/dichloromethane=2/1), obtain yellow solid 9-methoxyl group-6H-iso-indoles [2,1-a] indole-6-ketone 2f (78mg, 78%).
The sign data of this compound are as follows:1H NMR(CDCl3, 400MHz) and δ 3.87 (s, 3H), 6.55 (s, 1H), 6.77 (dd, J=
1.6,8.0Hz, 1H), 6.96 (d, J=1.6Hz, 1H), 7.13 (t, J=8.0Hz, 1H), 7.27 (t, J=8.0Hz, 1H),
7.43 (d, J=7.6Hz, 1H), 7.63 (d, J=8.4Hz, 1H), 7.86 (d, J=8.0Hz, 1H)；13C NMR(CDCl3,
100MHz)δ55.7,103.2,107.0,113.1,114.1,122.2,123.5,126.1,126.2,126.8,133.6,
134.3,136.9,138.4,162.4,.164.5.MS(ESI)m/z 250[M+H]+。
Embodiment 22
Method as described in embodiment 1, be sequentially added in the schlenk reaction tube of 15mL indole 1g (0.4mmol,
116mg), palladium (4.5mg, 0.02mmol), normal-butyl two (1-adamantyl) phosphine (BDAP) (21.5mg, 0.06mmol),
DABCO (134.6mg, 1.2mmol) and dimethyl sulfoxide (1.5mL), evacuation fills CO (1atm) three times, adds in 120 DEG C afterwards
Thermal agitation reaction 12h.After having reacted, adding saturated ammonium chloride solution cancellation reaction in reaction tube, dichloromethane extracts, has
Machine washs with deionized water and saturated nacl aqueous solution mutually, and anhydrous sodium sulfate is dried.Filter, be spin-dried for, cross silicagel column and separate (oil
Ether/dichloromethane=3/1), obtain yellow solid 9-fluoro-6H-iso-indoles [2,1-a] indole-6-ketone 2g (62mg, 65%).This change
The sign data of compound are as follows:1H NMR(CDCl3, 400MHz) and δ 6.64 (s, 1H), 7.01 (dt, J=2.0,8.8Hz, 1H),
7.15-7.20 (m, 2H), 7.29-7.33 (m, 1H), 7.47 (d, J=8.0Hz, 1H), 7.72-7.75 (m, 1H), 7.87-7.89
(m,1H)；13C NMR(CDCl3, 100MHz) and δ 104.5,109.0 (d, J=25.4Hz, 1C), 113.3,115.8 (d, J=
23.1Hz, 1C), 122.5,124.0,126.8,127.4 (d, J=10.4Hz, 1C), 129.7 (d, J=2.4Hz, 1C),
133.7,134.2,137.1 (d, J=11.1Hz, 1C), 137.4 (d, J=3.2Hz, 1C), 161.6,166.6 (d, J=
252.5Hz,1C).MS(ESI)m/z 238[M+H]+。
Embodiment 23
Method as described in embodiment 1, be sequentially added in the schlenk reaction tube of 15mL indole 1h (0.4mmol,
123mg), palladium (4.5mg, 0.02mmol), normal-butyl two (1-adamantyl) phosphine (BDAP) (21.5mg, 0.06mmol),
DABCO (134.6mg, 1.2mmol) and dimethyl sulfoxide (1.5mL), evacuation fills CO (1atm) three times, adds in 120 DEG C afterwards
Thermal agitation reaction 12h.After having reacted, adding saturated ammonium chloride solution cancellation reaction in reaction tube, dichloromethane extracts, has
Machine washs with deionized water and saturated nacl aqueous solution mutually, and anhydrous sodium sulfate is dried.Filter, be spin-dried for, cross silicagel column and separate (oil
Ether/dichloromethane=1/1), obtain yellow solid 9-chloro-6H-iso-indoles [2,1-a] indole-6-ketone 2h (68mg, 67%).This change
The sign data of compound are as follows:1H NMR(CDCl3, 400MHz) and δ 6.66 (s, 1H), 7.18 (t, J=7.2Hz, 1H), 7.28-
7.32 (m, 2H), 7.47-7.52 (m, 2H), 7.69 (d, J=8.0Hz, 1H), 7.90 (d, J=8.4Hz, 1H)；13C NMR
(CDCl3,100MHz)δ104.6,113.4,121.7,122.6,124.2,126.4,126.8,128.9,132.1,133.7,
134.2,136.2,137.4,140.3,161.6.MS(ESI)m/z 254[M+H]+。
Embodiment 24
Method as described in embodiment 1, be sequentially added in the schlenk reaction tube of 15mL indole 1i (0.4mmol,
128mg), palladium (9mg, 0.04mmol), normal-butyl two (1-adamantyl) phosphine (BDAP) (43mg, 0.12mmol), DABCO
(134.6mg, 1.2mmol) and dimethyl sulfoxide (1.5mL), evacuation fills CO (1atm) three times, afterwards in 120 DEG C of heated and stirred
Reaction 12h.After having reacted, adding saturated ammonium chloride solution cancellation reaction in reaction tube, dichloromethane extracts, and organic facies is used
Deionized water and saturated nacl aqueous solution washing, anhydrous sodium sulfate is dried.Filter, be spin-dried for, cross silicagel column and separate (petroleum ether/bis-
Chloromethanes=2/1), obtain yellow solid 9-chloro-3-methyl-6H-iso-indoles [2,1-a] indole-6-ketone 2i (81mg, 76%).Should
The sign data of compound are as follows:1H NMR(CDCl3, 400MHz) and δ 2.38 (s, 3H), 6.53 (s, 1H), 6.92 (d, J=
7.6Hz, 1H), 7.22 (dd, J=1.6,8.0Hz, 1H), 7.27 (d, J=8.0Hz, 1H), 7.41 (d, J=1.6Hz, 1H),
7.60 (d, J=8.0Hz, 1H), 7.65 (s, 1H)；13C NMR(CDCl3,150MHz)δ21.8,104.7,113.9,121.5,
122.2,125.5,126.4,128.6,131.9,132.1,134.1,136.3,136.8,137.5,140.2,161.7.HRMS
(ESI)calcd for C16H11NOCl[M+H]+268.0524,found 268.0540。
Embodiment 25
Method as described in embodiment 1, be sequentially added in the schlenk reaction tube of 15mL indole 1j (0.4mmol,
128mg), palladium (9mg, 0.04mmol), normal-butyl two (1-adamantyl) phosphine (BDAP) (43mg, 0.12mmol), DABCO
(134.6mg, 1.2mmol) and dimethyl sulfoxide (1.5mL), evacuation fills CO (1atm) three times, afterwards in 120 DEG C of heated and stirred
Reaction 12h.After having reacted, adding saturated ammonium chloride solution cancellation reaction in reaction tube, dichloromethane extracts, and organic facies is used
Deionized water and saturated nacl aqueous solution washing, anhydrous sodium sulfate is dried.Filter, be spin-dried for, cross silicagel column and separate (petroleum ether/bis-
Chloromethanes=3/1), obtain yellow solid 9-chloro-1-methyl-6H-iso-indoles [2,1-a] indole-6-ketone 2j (84mg, 79%).Should
The sign data of compound are as follows:1H NMR(CDCl3, 400MHz) and δ 2.42 (s, 3H), 6.63 (s, 1H), 6.91 (d, J=
7.6Hz, 1H), 7.14 (t, J=7.6Hz, 1H), 7.23 (dd, J=1.6,8.0Hz, 1H), 7.43 (d, J=1.6Hz, 1H),
7.61 (d, J=8.0Hz, 1H), 7.65 (d, J=8.0Hz, 1H)；13C NMR(CDCl3,150MHz)δ18.5,103.2,
111.0,121.5,124.8,126.4,126.9,128.8,132.1,132.3,133.5,133.9,136.3,136.8,
140.2,161.7.HRMS(ESI)calcd for C16H11NOCl[M+H]+268.0524,found 268.0543。
Embodiment above describes the ultimate principle of the present invention, principal character and advantage, the technical staff of the industry should
Understanding, the present invention is not restricted to the described embodiments, and the simply explanation present invention's described in above-described embodiment and description is former
Reason, under the scope without departing from the principle of the invention, the present invention also has various changes and modifications, and these changes and improvements each fall within
In the scope of protection of the invention.
Claims (3)
1. the method for atmospheric high efficiency synthesis 6H-iso-indoles [2, a 1-a] indole-6-ketone compounds, it is characterised in that: with 2-
(2-bromine aryl)-1H-Benzazole compounds and CO are initiation material, under the effect of transition metal palladium catalyst, part and alkali,
Target product 6H-iso-indoles [2,1-a] indole-6-ketone is prepared in organic solvent in 100-140 DEG C of heated and stirred reaction
Compound, the reaction equation in this synthetic method is:
Described transition metal palladium catalyst is PdCl2、Pd(PPh3)2Cl2、Pd2(dba)3Or Pd (OAc)2, part is BuPAd2、
X-Phos or [(t-Bu)3PH]BF4, alkali is DABCO or Et3N, organic solvent be dimethyl sulfoxide, DMF or
N-Methyl pyrrolidone.R in reaction equation1For hydrogen, methyl or chlorine, R2For hydrogen, methyl, methoxyl group, fluorine or chlorine.
The method of atmospheric high efficiency the most according to claim 1 synthesis 6H-iso-indoles [2,1-a] indole-6-ketone compounds,
It is characterized in that concretely comprising the following steps: under the CO atmosphere of 1atm, successively by 2-(2-bromine aryl)-1H-Benzazole compounds, transition
Metal palladium catalyst, part, alkali and organic solvent are added in Schlenk reaction tube, are then added in 100-140 DEG C by this mixture
Thermal agitation reaction 12h, after having reacted, adds saturated ammonium chloride solution cancellation reaction in reaction tube, and dichloromethane extracts, has
Machine spends ionized water and saturated nacl aqueous solution washing mutually successively, and anhydrous sodium sulfate is dried, and filters, is spin-dried for, and silica gel column chromatography divides
From obtaining target product 6H-iso-indoles [2,1-a] indole-6-ketone compounds.
The side of atmospheric high efficiency the most according to claim 1 and 2 synthesis 6H-iso-indoles [2,1-a] indole-6-ketone compounds
Method, it is characterised in that: described 2-(2-bromine aryl)-1H-Benzazole compounds, transition metal palladium catalyst, part and alkali
Molar ratio is 1:0.05-0.1:0.15-0.3:3.
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106866664A (en) * | 2017-03-16 | 2017-06-20 | 华南理工大学 | A kind of synthetic method of 6 Phenylindoles [2,1 a] isoquinoline compound |
| CN107556320A (en) * | 2017-09-11 | 2018-01-09 | 复旦大学 | The method of one kind synthesis 6H iso-indoles simultaneously ketone derivatives of [2,1 a] indoles 6 |
| CN108424416A (en) * | 2018-03-05 | 2018-08-21 | 河南师范大学 | A kind of method of synthesis of indole [1,2-c] quinazoline compounds |
| CN114805171A (en) * | 2022-05-05 | 2022-07-29 | 河南师范大学 | N-aryl indole compound and synthetic method thereof |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1998040416A1 (en) * | 1997-03-07 | 1998-09-17 | Targor Gmbh | Supported catalyst system, method for the production and use thereof in olefin polymerization |
| CN102482236A (en) * | 2009-09-11 | 2012-05-30 | 韩国化学研究院 | Indenone derivative and pharmaceutical composition comprising same |
| CN104892614A (en) * | 2015-05-27 | 2015-09-09 | 福建师范大学 | Synthesis method of 6H-isoindolo[2, 1-alpha]indol-6-one derivative |
-
2016
- 2016-08-26 CN CN201610735716.5A patent/CN106117216B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1998040416A1 (en) * | 1997-03-07 | 1998-09-17 | Targor Gmbh | Supported catalyst system, method for the production and use thereof in olefin polymerization |
| CN102482236A (en) * | 2009-09-11 | 2012-05-30 | 韩国化学研究院 | Indenone derivative and pharmaceutical composition comprising same |
| CN104892614A (en) * | 2015-05-27 | 2015-09-09 | 福建师范大学 | Synthesis method of 6H-isoindolo[2, 1-alpha]indol-6-one derivative |
Non-Patent Citations (3)
| Title |
|---|
| HUA-FENG HE，等: "Synthesis of 6H-isoindolo[2,1-a]indol-6-ones through a sequential copper-catalyzed C-N coupling and palladium-catalyzed C-H activation reaction", 《TETRAHEDRON》 * |
| MARINO A. CAMPO，等: "Synthesis of Fluoren-9-ones by the Palladium-Catalyzed Cyclocarbonylation of o-Halobiaryls", 《J. ORG. CHEM.》 * |
| TING TANG，等: "Divergent synthesis of 6H-isoindolo[2,1-a]indol-6-ones and indenoindolones: an investigation of Pd-catalyzed isocyanide insertion", 《TETRAHEDRON》 * |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106866664A (en) * | 2017-03-16 | 2017-06-20 | 华南理工大学 | A kind of synthetic method of 6 Phenylindoles [2,1 a] isoquinoline compound |
| CN107556320A (en) * | 2017-09-11 | 2018-01-09 | 复旦大学 | The method of one kind synthesis 6H iso-indoles simultaneously ketone derivatives of [2,1 a] indoles 6 |
| CN108424416A (en) * | 2018-03-05 | 2018-08-21 | 河南师范大学 | A kind of method of synthesis of indole [1,2-c] quinazoline compounds |
| CN114805171A (en) * | 2022-05-05 | 2022-07-29 | 河南师范大学 | N-aryl indole compound and synthetic method thereof |
| CN114805171B (en) * | 2022-05-05 | 2023-08-04 | 河南师范大学 | N-aryl indole compound and synthesis method thereof |
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