CN106967046A - A kind of preparation method of N heteroaryls hydroxycarbazole class compound - Google Patents
A kind of preparation method of N heteroaryls hydroxycarbazole class compound Download PDFInfo
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- CN106967046A CN106967046A CN201710321103.1A CN201710321103A CN106967046A CN 106967046 A CN106967046 A CN 106967046A CN 201710321103 A CN201710321103 A CN 201710321103A CN 106967046 A CN106967046 A CN 106967046A
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- 0 *c(cc1)cc2c1c1ccccc1[n]2C1=NCCC=C1 Chemical compound *c(cc1)cc2c1c1ccccc1[n]2C1=NCCC=C1 0.000 description 4
- IMRWILPUOVGIMU-UHFFFAOYSA-N Brc1ccccn1 Chemical compound Brc1ccccn1 IMRWILPUOVGIMU-UHFFFAOYSA-N 0.000 description 1
- DOHZIVDUKIELMO-UHFFFAOYSA-N C(c1ccccc1)Oc1ccc(c2ccccc2[nH]2)c2c1 Chemical compound C(c1ccccc1)Oc1ccc(c2ccccc2[nH]2)c2c1 DOHZIVDUKIELMO-UHFFFAOYSA-N 0.000 description 1
- BDSAGGKZNLTHAF-UHFFFAOYSA-N Cc1cc(O)ccc1-c(c(C(CC1=CC=CCN1)=C)c1)ccc1O Chemical compound Cc1cc(O)ccc1-c(c(C(CC1=CC=CCN1)=C)c1)ccc1O BDSAGGKZNLTHAF-UHFFFAOYSA-N 0.000 description 1
- GWPGDZPXOZATKL-UHFFFAOYSA-N Oc(cc1)cc2c1c1ccccc1[nH]2 Chemical compound Oc(cc1)cc2c1c1ccccc1[nH]2 GWPGDZPXOZATKL-UHFFFAOYSA-N 0.000 description 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
Abstract
The invention discloses a kind of preparation method of N heteroaryls hydroxycarbazole class compound, described method is carried out as follows：Under nitrogen protection, using N heteroaryl carbazole halide-based compounds as raw material, Cu salt is catalyst, N1,N2Double (4 hydroxyls 2,6 xylyls) oxamides be part, under alkaline matter effect, in a solvent, in reaction 1 72 hours at 80 110 DEG C, described N heteroaryl carbazole halide-based compounds post-treated N heteroaryl hydroxycarbazole class compounds for respectively obtaining target product as shown in formula (I), (II), (III) or (IV) of reaction solution obtained by as shown in formula (1), formula (2), formula (3) or formula (4)；
Description
Technical field
The present invention relates to a kind of preparation method of the miscellaneous hydroxycarbazole class compounds of N-.
Background technology
N- heteroaryl -2- hydroxycarbazole class compounds are four ring gear metal platinums of synthesis and palladium complex phosphor material molecule pole
For important intermediate, it is widely used among the synthesis of this quasi-molecule.Four ring gear metal platinums and palladium complex are due to its center
Strong spin coupling effect between heavy metal ion and organic ligand, being at excited singlet or electronics can effectively enter
Leap up more between row system and return to excited triplet state, turn while the molecule in excited triplet state can be allow to carry out efficient eradiation
Change, which releases energy, returns to ground state, so that phosphorescence can be efficiently sent at room temperature, and phosphorescence quantum efficiency can be up to
100%, so that this kind of metal organic complex can be as organic electroluminescent phosphorescence luminescent material in display and lighting field
Have a wide range of applications.Wherein N- (2- pyridine radicals) carbazole structure unit is widely present in this four ring gears metal platinum and palladium
Among complex, and the photophysical property to this quasi-molecule, chemical stability and thermodynamic stability have important influence
(Angew.Chem.Int.Ed.2013,52,6753；Org. Electronics,2014,15,1862；Adv.Mater.2014,
26,7116；ACS Appl.Mater.&Interfaces,2015,7,16240；Adv.Optical Mater. 2015,3,
390；Adv.Mater.2015,27,2533；US 20130168656；WO 2014031977；US 20160359125).Recently,
The Jian Li professors group that State of Arizona, US founds university reports stable and efficiently full hexatomic ring chelating four ring gears gold
Belong to platinum complex phosphorescent devices, for blue phosphorescent device further development provide new direction (Chem. Mater.2016,
28,3276), and N- heteroaryl hydroxycarbazole class compounds exactly synthesize the indispensable important intermediate of this quasi-molecule (formula I).
N- heteroaryl -2- hydroxycarbazole class compound synthesis the methods reported in current document mainly have following two,
One is U.S. Universal Display Corporation (UDC) report with adjacent nitro iodobenzene and to methoxybenzene boron
Acid is raw material, and 2'- nitro -4- methoxyl biphenyls 1 are generated by the Suzuki coupling reactions of zeroth order palladium chtalyst；Then with three second
Epoxide phosphorus is that reducing agent and solvent carry out ring closure reaction generation 2- methoxyl carbazoles 2；Then zeroth order palladium is passed through with 2- iodine pyridines again
The coupling reaction of the C-N keys of catalysis obtains N- (2- pyridine radicals) -2- methoxyl carbazoles 3；It is last that methyl generation is taken off at 200 DEG C
Target product N- (2- pyridine radicals) -2- hydroxycarbazoles 4 (route 1) (US 20130168656).This synthetic route has following deficiency
Part：First, needing four-step reaction, total recovery is low, only 22%；Second, wherein there is two steps to need to use the high zeroth order of price
Palladium catalyst；Third, have two-step reaction temperature very high, respectively 165 DEG C and 200 DEG C；Fourth, being needed when introducing pyridine groups
Use expensive 2- iodine pyridines.
Second method is that State of Arizona, US stands university Jian Li professors and Guijie Li were reported in 2014
Using 2- hydroxycarbazoles as raw material, with intermediate 5 is obtained after benzyl protection hydroxyl, then it is coupled by the Suzuki of zeroth order palladium chtalyst
N- [2- (4- tert .-butylpyridines base)] -2- benzyloxies carbazole 6 is generated with the 4- tert-butyl groups-bromopyridine reaction, finally with the three of equivalent
Boron fluoride takes off benzyl and obtains target product N- [2- (4- tert .-butylpyridines base)] -2- hydroxycarbazoles 7 (route 2)
(Adv.Mater.2014,26,7116).Jian Li professors in 2016 and Guijie Li report N- (2- with similar method
Pyridine radicals) -2- hydroxycarbazoles 4 synthesis (route 3) (US 20160359125).Although both approaches are than route 1 efficiently,
It is also to have weak point, first, raw materials used 2- hydroxycarbazoles are expensive, is unfavorable for a large amount of preparations of reaction；Second, wherein
Also need to use the high zero valent palladium catalyst of price and part JohnPhos；Thirdly, it is necessary to making blocking group of benzyl, totally
For Atom economy it is poor.
Therefore, a kind of method that is cheap, efficiently preparing N- heteroaryl -2- hydroxycarbazole class compounds how is developed, for
The exploitation of phosphor material, the development of four ring gear metal platinum complex phosphor materials of especially full hexatomic ring chelating will be played greatly
Facilitation.
Aryl bromide is relatively cheap to be easy to get, and is changed into if can realize and aryl bromide is directly carried out to functional group's conversion
Hydroxyl, a kind of easy and efficient method is provided by the synthesis for hydroxy arene class compound.The groups such as Buchwald, Beller
Realize the Metal Palladium compound for catalysis aryl halide under the auxiliary of the Phosphine ligands of big steric hindrance and prepare hydroxy arene class compound.
But it is due to the expensive of Phosphine ligands and metal palladium compound, applies it, especially for the reaction for needing largely to prepare
Be very limited (J.Am.Chem.Soc.2006,128,10694； Angew.Chem.,Int.Ed.2009,48,918；
Angew.Chem.,Int.Ed. 2009,48,7595).And such function of the cheap metal copper compound catalysis developed at present
The conversion reaction of group is substantially only limited to substrate structure simple, the smaller aryl iodide of steric hindrance and bromide, and catalyst and matches somebody with somebody
The large usage quantity of body, reaction temperature is also higher, can not especially realize N- heteroaryls -2- bromines carbazole compound to N- heteroaryls
The functional group conversions of base -2- hydroxycarbazole class compounds, significantly limit such reaction in fields such as functional material preparations
Using.
In summary, although Metal Palladium and the aryl halide of copper compound catalysis are converted into hydroxy arene class compound
Reaction has been developed, but is converted into N- heteroaryl -2- hydroxycarbazole classes by N- heteroaryl -2- bromine carbazole compounds
Compound is reacted there is not yet document report, and N- heteroaryl -2- hydroxycarbazole class compounds are four ring gear metal platinums of synthesis and palladium
The important intermediate of complex phosphorescence material, therefore how to realize the Efficient Conversion of such compound by the synthesis to phosphor material
Important impetus is played in development, can be greatly promoted the development of the association areas such as OLED.
The content of the invention
It is an object of the invention to provide a kind of preparation method of N- heteroaryls hydroxycarbazole class compound.This method can be with
Inexpensively, succinctly, be efficiently synthesized N- heteroaryl hydroxycarbazole class Compound Compounds, it is possible to achieve such compound gram level is even
A greater amount of preparations, is greatly promoted application of such reaction in terms of phosphor material synthesis, can be greatly promoted OLED
Etc. the development of association area.
The technical solution adopted by the present invention is as follows：
A kind of preparation method of N- heteroaryls hydroxycarbazole class compound, described method is carried out as follows：In nitrogen
Under gas shielded, using N- heteroaryl carbazole halide-based compounds as raw material, Cu salt is catalyst, N1,N2- bis- (4- hydroxyls -2,6-
Xylyl) oxamides be part, alkaline matter effect under, in a solvent, at 80-110 DEG C react 1-72 hours, it is described
N- heteroaryl carbazoles halide-based compound such as formula (1), formula (2), gained reaction solution shown in formula (3) or formula (4) it is post-treated
Respectively obtain N- heteroaryl hydroxycarbazole class compound of the target product as shown in formula (I), (II), (III) or (IV)；Described
N- heteroaryl carbazole halide-based compounds and N shown in formula (1), formula (2), formula (3) or formula (4)1,N2- bis- (4- hydroxyl -2,
6- xylyls) oxamides, the ratio between the amount of material of alkaline matter be：1:0.01~0.1：1.0~5.0；The part N1,N2-
The ratio between double (4- hydroxyl -2,6- xylyls) oxamides and Cu (I) or Cu (II) salt catalyst material amount is 1~5:1；
The R1-R12Each stand alone as H or bromine, described R1、R2、R3In at least one be bromine, described R4、R5、R6
In at least one be bromine, described R7、R8、R9In at least one be bromine, described R10、R11、R12In at least one be
Bromine, described Z is CH or N, X are fluorine, chlorine or bromine；Described R1-R12Any of when being hydrogen, it is corresponding in target product
G1-G12Also it is hydrogen；Described R1-R9Any of when being bromine, corresponding G in target product1-G9For hydroxyl；Described R10-
R12Any of be bromine, and described X is when being fluorine or chlorine, corresponding G in target product10-G12For bromine；Described R10-R12
Any of be bromine, and described X is when being bromine, corresponding G in target product10-G12For hydroxyl.
Further, the N- heteroaryl carbazole halogenation species chemical combination shown in described formula (1), formula (2), formula (3) or formula (4)
Thing is：The bromo- 9- of 2- (2- (the bromo- pyridine radicals of 4-)) carbazole, the bromo- 9- of 2,6- bis- (2- pyridine radicals) carbazoles or bromo- 9- (2- of 2,6- bis-
Pyrimidine radicals) carbazole.
Further, described catalyst Cu salt be stannous chloride, cuprous bromide, cuprous iodide, copper acetate or copper sulphate and
Their own hydrate.
Further, described alkaline matter be lithium hydroxide, sodium hydroxide, potassium hydroxide, tert-butyl alcohol lithium, sodium tert-butoxide,
Potassium tert-butoxide, sodium methoxide, caustic alcohol, cesium carbonate, potassium carbonate or potassium phosphate.
Further, described solvent is the mixing of two kinds of any ratios of DMF or dimethyl sulfoxide (DMSO)/water
Thing.
Further, total addition of the solvent be calculated as 1 with the amount of the material of N- heteroaryl bromide carbazole compounds~
100mL/mmol。
Further, preferred described N- heteroaryl bromide carbazole compounds and N1,N2- bis- (4- hydroxyl -2,6- dimethylbenzene
Base) oxamides, the ratio between the amount of material of alkaline matter be： 1:0.01~0.05：1.5~3.0.
Further, preferably described part N1,N2- bis- (4- hydroxyl -2,6- xylyls) oxamides and Cu (I) or Cu
(II) the ratio between amount of salt catalyst material is 1:1.
The post-processing approach of reaction of the present invention is：After reaction terminates, the cooling of question response liquid is extracted with ethyl acetate,
Merge organic phase, anhydrous sodium sulfate drying, filtering, vacuum distillation removes solvent, gained crude product is separated by silica gel column chromatography
Purifying, obtains target product.
Compared with prior art, beneficial effects of the present invention are embodied in：
(1) target product N- heteroaryl hydroxycarbazole class compound convenience and high-efficiencies are synthesized, reactions steps are greatly shortened；
(2) the raw material N- heteroaryls carbazole halide-based compound is easily prepared, and required raw material can be with cheap click
The step of coupling reaction one of the C-N keys of azoles halide and 2- bromopyridine classes compound by the CuCl catalysis developed before us is closed
Into, and high income, it is easy to it is extensive to prepare (CN 201610769719.0；J.Org.Chem.2017,82,1024；See below formula).
Wherein 2- bromines carbazole (500 grams/3600 yuan) price well below in route 2 and route 3 initiation material 2- hydroxycarbazoles (5 grams/
465 yuan).
(3) inexpensive catalyst is easy to get, and can be not only cuprous iodide, it might even be possible to use more economic protobromide
Copper, stannous chloride or copper acetate.
(4) reaction dissolvent without being handled, reaction process and simple to operate, high income be up to 98% and suitable for a large amount of systems
Standby and industrialization, has broad application prospects.
(5) blue emitting phosphor material PtNON and PtNON can be easily and efficiently synthesized using this reaction, while being such phosphorus
The preparation of luminescent material provides a kind of synthetic method of economical and efficient the most.
Embodiment
Below by specific embodiment, the invention will be further described, but protection scope of the present invention is not limited in
This.
Embodiment 1：The preparation of the bromo- 9- of 2- (2- (4- hydroxy-pyridyls)) carbazole
Into the dry reaction pipe with magnetic rotor, the bromo- 9- of 2- (2- (the fluoro- pyridine radicals of 4-)) carbazole is sequentially added
(343.2mg, 1.0mmol, 1.0eq), stannous chloride (5.0mg, 0.05mmol, 0.05eq), part N1,N2- bis- (4- hydroxyls-
2,6- xylyls) oxamides (16.4mg, 0.05mmol, 0.05eq), a hydronium(ion) lithia (88.1mg, 2.10 mmol,
2.1eq) substitute nitrogen three times, then add DMSO (2.0mL) and deionized water (0.5mL).Reactant mixture in 100 DEG C next time
Stream 24 hours, TLC thin-layer chromatographys monitoring 2- bromo- 9- (2- (the fluoro- pyridine radicals of 4-)) carbazole carbazole.Cooling, successively respectively to reaction
System adds 100.0mL ethyl acetate and 50.0mL deionized waters, and transfers them to separatory funnel point liquid, ethyl acetate extraction
(50mL × 2), merge organic phase, and anhydrous sodium sulfate drying, filtering, vacuum distillation removes solvent, gained crude product is passed through into silica gel
Column chromatography separating purification, eluent (petrol ether/ethyl acetate=3:1-1:1) white solid 93mg, yield 33%, are obtained.1H
NMR(500MHz,DMSO-d6):δ 6.90 (dd, J=5.5,2.0Hz, 1H), 7.10 (d, J=2.0Hz, 1H), 7.33-7.36
(m, 1H), 7.48 (dd, J=8.0,2.0Hz, 1H), 7.49-7.52 (m, 1H), 7.77 (d, J=8.0Hz, 1H), 7.98 (d,
J=1.5Hz, 1H), 8.21 (d, J=7.5Hz, 1H), 8.27 (d, J=2.5 Hz, 1H), 8.44 (d, J=5.5Hz, 1H),
11.89(s,1H).13C NMR(100 MHz,DMSO-d6):δ106.06,110.63,111.34,114.18,118.86,
120.59,121.19,122.06,122.49,122.69,123.52,126.81,139.03, 139.76,150.51,
151.58,166.21.HRMS(ESI):calcd for C17H12BrN2O [M+H]+339.0128,found 339.0167.
Embodiment 2：The preparation of the bromo- 9- of 2- (2- (4- hydroxy-pyridyls)) carbazole
Into the dry reaction pipe with magnetic rotor, the bromo- 9- of 2- (2- (the fluoro- pyridine radicals of 4-)) carbazole is sequentially added
(168.4mg, 0.49mmol, 1.0eq), stannous chloride (2.43mg, 0.03mmol, 0.05eq), part N1,N2- bis- (4- hydroxyls
Base -2,6- xylyl) oxamides (8.2mg, 0.03mmol, 0.05eq), sodium tert-butoxide (98.9mg, 1.03mmol,
2.1eq) substitute nitrogen three times, then add DMSO (2.0mL) and deionized water (0.5 mL).Reactant mixture is at 110 DEG C
Backflow 24 hours, TLC thin-layer chromatographys monitoring 2- bromo- 9- (2- (the fluoro- pyridine radicals of 4-)) carbazole.Cooling, successively respectively to reactant
System adds 25.0mL ethyl acetate and 25.0mL deionizations H2O is fully cleaned, and transfers them to separatory funnel point liquid, acetic acid
Ethyl ester extracts (25mL × 2), merges organic phase, anhydrous sodium sulfate drying, filtering, vacuum distillation removes solvent, by gained crude product
Pass through silica gel column chromatogram separating purification, eluent (petrol ether/ethyl acetate=3:1-1:1) white solid 74.3mg, yield, are obtained
55%.Product is passed through1H NMR confirm consistent with data in embodiment 46.
Embodiment 3：The preparation of the bromo- 9- of 2- (2- (4- hydroxy-pyridyls)) carbazole
The bromo- 9- of 2- (2- (the chloro- pyridine radicals of 4-)) carbazole is sequentially added into the dry reaction pipe with magnetic rotor
(89.4mg, 0.25mmol, 1.0eq), stannous chloride (1.3mg, 0.01 mmol, 0.05eq), part N1,N2- bis- (4- hydroxyls-
2,6- xylyls) oxamides (4.1 mg, 0.01mmol, 0.05eq), sodium hydroxide (21.0mg, 0.53mmol, 2.1eq)
Substitute nitrogen three times, then add DMSO (2.0mL) and deionized water (0.5mL).Reactant mixture is small in backflow 24 at 110 DEG C
When, TLC thin-layer chromatographys monitoring 2- bromo- 9- (2- (the chloro- pyridine radicals of 4-)) carbazole.Cooling, is added to reaction system respectively successively
25.0mL ethyl acetate and 25.0mL deionized waters, and transfer them to separatory funnel point liquid, ethyl acetate extraction (25mL ×
2) organic phase, is merged, anhydrous sodium sulfate drying, filtering, vacuum distillation removes solvent, and gained crude product is passed through into silica gel column chromatography point
From purifying, eluent (petrol ether/ethyl acetate=3:1-1:1) white solid 52.9mg, yield 72%, are obtained.Product is passed through1H
NMR confirms consistent with data in embodiment 46.
Embodiment 4：The preparation of the bromo- 9- of 2- (2- (4- hydroxy-pyridyls)) carbazole
The bromo- 9- of 2- (2- (the chloro- pyridine radicals of 4-)) carbazole is sequentially added into the dry reaction pipe with magnetic rotor
(89.4mg, 0.25mmol, 1.0eq), stannous chloride (1.3mg, 0.01 mmol, 0.05eq), part N1,N2- bis- (4- hydroxyls-
2,6- xylyls) oxamides (4.1 mg, 0.01mmol, 0.05eq), sodium hydroxide (21.0mg, 0.53mmol, 2.1eq)
Substitute nitrogen three times, then add DMSO (2.0mL) and deionized water (0.5mL).Reactant mixture is small in backflow 24 at 110 DEG C
When, TLC thin-layer chromatographys monitoring 2- bromo- 9- (2- (the chloro- pyridine radicals of 4-)) carbazole.Cooling, is added to reaction system respectively successively
25.0mL ethyl acetate and 25.0mL deionized waters, and transfer them to separatory funnel point liquid, ethyl acetate extraction (25mL ×
2) organic phase, is merged, anhydrous sodium sulfate drying, filtering, vacuum distillation removes solvent, and gained crude product is passed through into silica gel column chromatography point
From purifying, eluent (petrol ether/ethyl acetate=3:1-0:1) white solid 19.2mg, yield 28%, are obtained.Product is passed through1H
NMR: (500MHz,DMSO-d6):δ 6.77 (dd, J=8.5,2.0Hz, 1H), 6.86 (dd, J=6.0,2.0Hz, 1H),
7.03 (d, J=2.0Hz, 1H), 7.18 (d, J=2.0Hz, 1H), 7.21-7.24 (m, 1H), 7.31 (td, J=7.5,1.5Hz,
1H), 7.69 (d, J=8.5Hz, 1H), 7.97 (d, J=8.0Hz, 1H), 8.04 (d, J=7.5Hz, 1H), 8.40 (d, J=
5.5Hz,1H),9.58(s,1H),11.10 (s,1H).
Apply example 5：The preparation of 2- hydroxyls -9- (2- (4- hydroxy-pyridyls)) carbazole
The bromo- 9- of 2- (2- (the bromo- pyridine radicals of 5-)) carbazole is sequentially added into the dry reaction pipe with magnetic rotor
(100.5mg, 0.25mmol, 1.0eq), stannous chloride (2.5mg, 0.03 mmol, 0.10eq), part N1,N2- bis- (4- hydroxyls-
2,6- xylyls) oxamides (8.2 mg, 0.03mmol, 0.10eq), sodium tert-butoxide (100.9mg, 1.05mmol, 4.2eq)
Substitute nitrogen three times, then add DMSO (2.0mL) and deionized water (1.0mL).Reactant mixture is small in backflow 24 at 110 DEG C
When, TLC thin-layer chromatographys monitoring 2- bromo- 9- (2- (the bromo- pyridine radicals of 5-)) carbazole.Cooling, is added to reaction system respectively successively
25.0mL ethyl acetate and 25.0mL deionized waters, and transfer them to separatory funnel point liquid, ethyl acetate extraction (25mL ×
3) organic phase, is merged, anhydrous sodium sulfate drying, filtering, vacuum distillation removes solvent, and gained crude product is passed through into silica gel column chromatography point
From purifying, eluent (petrol ether/ethyl acetate=4:1-1:1) white solid 43.8mg, yield 63%, are obtained.1H NMR
(500MHz, DMSO-d6):δ 6.74 (dd, J=8.0,2.0Hz, 1H), 6.94 (d, J=2.0 Hz, 1H), 7.19-7.22 (m,
1H), 7.29 (td, J=7.0,1.0Hz, 1H), 7.47-7.49 (m, 2H), 7.53 (d, J=8.5Hz, 1H), 7.97 (d, J=
8.5 Hz, 1H), 8.03 (d, J=7.5Hz, 1H), 8.23-8.24 (m, 1H), 9.54 (s, 1H), 10.27 (s, 1H) .HRMS
(ESI):calcd for C17H13N2O2[M+H]+ 277.0972,found 277.0983.
Embodiment 6：The preparation of the bromo- 9- of 2- hydroxyls -7- (2- pyridine radicals) carbazole
2,6- bis- bromo- 9- (2- pyridine radicals) carbazole is sequentially added into the dry reaction pipe with magnetic rotor
(61.3mg, 0.15mmol, 1.0eq), stannous chloride (1.5mg, 0.015mmol, 0.10eq), part N1,N2- bis- (4- hydroxyls-
2,6- xylyls) oxamides (4.9mg, 0.015mmol, 0.10eq), a hydronium(ion) lithia (26.4mg, 0.63mmol,
4.2 eq) substitute nitrogen three times, then add DMSO (2.0mL) and deionized water (0.5mL).Reactant mixture is at 100 DEG C
Backflow 48 hours, TLC thin-layer chromatographys monitoring 2,6- bis- bromo- 9- (2- pyridine radicals) carbazole.Cooling, successively respectively to reaction system
25.0mL ethyl acetate and 25.0mL deionized waters are added, and transfers them to separatory funnel point liquid, ethyl acetate extraction (25mL
× 3), merge organic phase, anhydrous sodium sulfate drying, filtering, vacuum distillation removes solvent, gained crude product is passed through into silica gel column chromatography
Isolate and purify, eluent (petrol ether/ethyl acetate=3:1) white solid 24.5mg, yield 49%, are obtained.1H NMR
(500MHz, DMSO-d6):δ 6.82 (dd, J=8.5,2.0Hz, 1H), 7.12 (d, J=2.0 Hz, 1H), 6.82 (dd, J=
8.5,2.0Hz, 1H), 7.41 (dd, J=8.0,2.0 Hz, 1H), 7.51 (ddd, J=7.5,5.0,1.0Hz, 1H), 7.78 (d,
J=8.0 Hz, 1H), 7.86 (d, J=1.5Hz, 1H), 8.04 (dd, J=8.0,2.5Hz, 1H), 8.14 (td, J=8.0,
2.0Hz,1H),8.74-8.76(m,1H),9.74 (s,1H).13C NMR(100MHz,DMSO-d6):δ96.99,110.92,
113.62, 115.19,117.03,119.15,120.89,121.57,122.33,123.26,123.61, 139.65,
139.68,140.77,149.66,150.34,157.54.HRMS(ESI): calcd for C17H12BrN2O[M+H]+
339.0128,found 339.0128.
Embodiment 7：The preparation of 2,7- dihydroxy -9- (2- pyridine radicals) carbazole
Sequentially added into the dry reaction pipe with magnetic rotor 2,6- bis- bromo- 9- (2- pyridine radicals) carbazole (80.4mg,
0.20mmol, 1.0eq), stannous chloride (2.0mg, 0.02 mmol, 0.10eq), part N1,N2- bis- (4- hydroxyl -2,6- diformazans
Phenyl) oxamides (6.5 mg, 0.02mmol, 0.10eq), sodium hydroxide (33.6mg, 0.84mmol, 4.2eq) substitutes nitrogen
Three times, then add DMSO (2.0mL) and deionized water (1.0mL).Reactant mixture at 110 DEG C in reacting 24 hours, and TLC is thin
Layer chromatography monitors 2,6- bis- bromo- 9- (2- pyridine radicals) carbazole.Cooling, adds 25.0mL acetic acid second to reaction system respectively successively
Ester and 25.0mL deionized waters, and separatory funnel point liquid is transferred them to, ethyl acetate extraction (25 mL × 3) merges organic
Phase, anhydrous sodium sulfate drying, filtering, vacuum distillation removes solvent, and gained crude product is passed through into silica gel column chromatogram separating purification, elution
Agent (petrol ether/ethyl acetate=3:1) white solid 16.5mg, yield 24%, are obtained.1H NMR(500MHz,DMSO-d6): δ
6.71 (dd, J=8.0,2.0Hz, 2H), 7.10 (d, J=2.0Hz, 2H), 7.45 (ddd, J=7.5,5.0,1.0Hz, 1H),
7.70 (d, J=3.0Hz, 1H), 7.80 (d, J=3.5Hz, 2H), 8.10 (td, J=8.0,2.0Hz, 1H), 8.72 (ddd, J
=5.0,2.0,0.5Hz, 1H), 9.39 (s, 2H) .HRMS (ESI):calcd for C17H13N2O2[M+H]+277.0972,
found 277.0961.
Embodiment 8：The preparation of 2,7- dihydroxy -9- (2- pyridine radicals) carbazole
2,6- bis- bromo- 9- (2- pyridine radicals) carbazole is sequentially added into the dry reaction pipe with magnetic rotor
(100.5mg, 0.25mmol, 1.0eq), stannous chloride (2.5mg, 0.03 mmol, 0.10eq), part N1,N2- bis- (4- hydroxyls-
2,6- xylyls) oxamides (8.2 mg, 0.03mmol, 0.10eq), sodium tert-butoxide (100.9mg, 1.05mmol, 4.2eq)
Substitute nitrogen three times, then add DMSO (2.0mL) and deionized water (1.0mL).Reactant mixture is small in reaction 24 at 110 DEG C
When, TLC thin-layer chromatographys monitoring 2,6- bis- bromo- 9- (2- pyridine radicals) carbazole.Cooling, is added to reaction system respectively successively
25.0mL ethyl acetate and 25.0mL deionized waters, and transfer them to separatory funnel point liquid, ethyl acetate extraction (25 mL ×
3) organic phase, is merged, anhydrous sodium sulfate drying, filtering, vacuum distillation removes solvent, and gained crude product is passed through into silica gel column chromatography point
From purifying, eluent (petrol ether/ethyl acetate=3:1) white solid 55.8mg, yield 81%, are obtained.Product is passed through1H NMR are true
Recognize consistent with data in embodiment 51.
Embodiment 9：The preparation of 2,6- dihydroxy -9- (2- pyrimidine radicals) carbazole
2,6- bis- bromo- 9- (2- pyrimidine radicals) carbazole is sequentially added into the dry reaction pipe with magnetic rotor
(100.8mg, 0.25mmol, 1.0eq), stannous chloride (2.5mg, 0.03 mmol, 0.10eq), part N1,N2- bis- (4- hydroxyls-
2,6- xylyls) oxamides (8.2 mg, 0.03mmol, 0.10eq), a hydronium(ion) lithia (44.1mg, 1.05mmol,
4.2eq) substitute nitrogen three times, then add DMSO (2.0mL) and deionized water (1.0 mL).Reactant mixture is at 110 DEG C
Reaction 24 hours, TLC thin-layer chromatographys monitoring 2,6- bis- bromo- 9- (2- pyrimidine radicals) carbazole.Cooling, adds to reaction system respectively successively
Enter 25.0mL ethyl acetate and 25.0mL deionized waters, and transfer them to separatory funnel point liquid, ethyl acetate extraction (25mL ×
3) organic phase, is merged, anhydrous sodium sulfate drying, filtering, vacuum distillation removes solvent, and gained crude product is passed through into silica gel column chromatography point
From purifying, eluent (petrol ether/ethyl acetate=3:1-1:1) white solid 42.8mg, yield 62%, are obtained.1H NMR(500
MHz,DMSO-d6):δ 6.77 (dd, J=8.5,2.0Hz, 2H), 7.38 (t, J=5.0Hz, 1H), 7.78 (d, J=8.0Hz,
2H), (s, the 2H) .HRMS (ESI) of 8.19 (d, J=2.5Hz, 2H), 8.97 (d, J=4.5Hz, 2H), 9.45:calcd for
C16H12N3O2[M+H]+278.0924,found 278.0916。
Claims (9)
1. a kind of preparation method of N- heteroaryls hydroxycarbazole class compound, described method is carried out as follows：In nitrogen
Under protection, using N- heteroaryl carbazole halide-based compounds as raw material, Cu salt is catalyst, N1,N2- bis- (4- hydroxyls -2,6- two
Tolyl) oxamides be part, alkaline matter effect under, in a solvent, at 80-110 DEG C react 1-72 hours, it is described
N- heteroaryl carbazoles halide-based compound post-treated point of reaction solution of gained for example shown in formula (1), formula (2), formula (3) or formula (4)
N- heteroaryl hydroxycarbazole class compound of the target product as shown in formula (I), (II), (III) or (IV) is not obtained；Described formula
(1), the N- heteroaryl carbazole halide-based compounds and N shown in formula (2), formula (3) or formula (4)1,N2- bis- (4- hydroxyls -2,6- two
Tolyl) oxamides, the ratio between the amount of material of alkaline matter be：1:0.01~0.1：1.0~5.0；The part N1,N2- bis-
The ratio between (4- hydroxyl -2,6- xylyls) oxamides and Cu (I) or Cu (II) salt catalyst material amount is 1~5:1；
The R1-R12Each stand alone as H or bromine, described R1、R2、R3In at least one be bromine, described R4、R5、R6In extremely
Rare one is bromine, described R7、R8、R9In at least one be bromine, described R10、R11、R12In at least one be bromine, institute
The Z stated is CH or N, X are fluorine, chlorine or bromine；Described R1-R12Any of when being hydrogen, corresponding G in target product1-G12
For hydrogen；Described R1-R9Any of when being bromine, corresponding G in target product1-G9For hydroxyl；Described R10-R12In it is any
Individual is bromine, and described X is when being fluorine or chlorine, corresponding G in target product10-G12For bromine；Described R10-R12Any of be
Bromine, and described X is when being bromine, corresponding G in target product10-G12For hydroxyl.
2. according to a kind of preparation method of N- heteroaryls hydroxycarbazole class compound described in claim 1, it is characterised in that：Institute
The N- heteroaryl carbazole halide-based compounds shown in formula (1), formula (2), formula (3) or formula (4) stated are：The bromo- 9- of 2- (2- (4-
Bromo- pyridine radicals)) carbazole, the bromo- 9- of 2,6- bis- (2- pyridine radicals) carbazoles or 2,6- bis- bromo- 9- (2- pyrimidine radicals) carbazole.
3. according to a kind of preparation method of N- heteroaryls hydroxycarbazole class compound described in claim 1, it is characterised in that：Institute
The catalyst Cu salt stated is stannous chloride, cuprous bromide, cuprous iodide, copper acetate or copper sulphate and their own hydrate.
4. according to a kind of preparation method of N- heteroaryls hydroxycarbazole class compound described in claim 1, it is characterised in that：Institute
The alkaline matter stated is lithium hydroxide, sodium hydroxide, potassium hydroxide, tert-butyl alcohol lithium, sodium tert-butoxide, potassium tert-butoxide, sodium methoxide, second
Sodium alkoxide, cesium carbonate, potassium carbonate or potassium phosphate.
5. according to a kind of preparation method of N- heteroaryls hydroxycarbazole class compound described in claim 1, it is characterised in that：Institute
The solvent stated is the mixture of two kinds of any ratios of N,N-dimethylformamide or dimethyl sulfoxide (DMSO)/water.
6. according to a kind of preparation method of N- heteroaryls hydroxycarbazole class compound described in claim 1, it is characterised in that：Institute
State total addition of solvent and 1~100mL/mmol is calculated as with the amount of the material of N- heteroaryl bromide carbazole compounds.
7. according to a kind of preparation method of N- heteroaryls hydroxycarbazole class compound described in claim 1, it is characterised in that：Institute
The N- heteroaryl bromide carbazole compounds and N stated1,N2- bis- (4- hydroxyl -2,6- xylyls) oxamides, the material of alkaline matter
The ratio between amount be：1:0.01~0.05：1.5~3.0.
8. according to a kind of preparation method of N- heteroaryls hydroxycarbazole class compound described in claim 1, it is characterised in that：Institute
The part N stated1,N2The ratio between-bis- (4- hydroxyl -2,6- xylyls) oxamides and amount of Cu (I) or Cu (II) salt catalyst material
For 1:1.
9. according to a kind of preparation method of N- heteroaryls hydroxycarbazole class compound described in claim 8, it is characterised in that：Instead
The post-processing approach answered is：After reaction terminates, the cooling of question response liquid is extracted with ethyl acetate, merges organic phase, anhydrous sodium sulfate
Dry, filtering, vacuum distillation removes solvent, by gained crude product by silica gel column chromatogram separating purification, obtains target product.
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20130168656A1 (en) * | 2012-01-03 | 2013-07-04 | Universal Display Corporation | Cyclometallated tetradentate platinum complexes |
| WO2014153043A1 (en) * | 2013-03-14 | 2014-09-25 | Health Research, Inc. | Compounds and methods for treating cancers |
| US20160359125A1 (en) * | 2015-06-03 | 2016-12-08 | Arizona Board Of Regents On Behalf Of Arizona State University | Tetradentate and octahedral metal complexes containing naphthyridinocarbazole and its analogues |
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2017
- 2017-05-09 CN CN201710321103.1A patent/CN106967046A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20130168656A1 (en) * | 2012-01-03 | 2013-07-04 | Universal Display Corporation | Cyclometallated tetradentate platinum complexes |
| WO2014153043A1 (en) * | 2013-03-14 | 2014-09-25 | Health Research, Inc. | Compounds and methods for treating cancers |
| US20160359125A1 (en) * | 2015-06-03 | 2016-12-08 | Arizona Board Of Regents On Behalf Of Arizona State University | Tetradentate and octahedral metal complexes containing naphthyridinocarbazole and its analogues |
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