CN108947900A - The method of carbon arylation tandem reaction synthesizing heterocyclic compound of the photoinduction without metal catalytic - Google Patents
The method of carbon arylation tandem reaction synthesizing heterocyclic compound of the photoinduction without metal catalytic Download PDFInfo
- Publication number
- CN108947900A CN108947900A CN201810885686.5A CN201810885686A CN108947900A CN 108947900 A CN108947900 A CN 108947900A CN 201810885686 A CN201810885686 A CN 201810885686A CN 108947900 A CN108947900 A CN 108947900A
- Authority
- CN
- China
- Prior art keywords
- formula
- reaction
- heterocyclic compound
- photoinduction
- metal catalytic
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
- C07D217/22—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the nitrogen-containing ring
- C07D217/24—Oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/76—Benzo[c]pyrans
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Abstract
The invention belongs to technical field of organic synthesis, disclose a kind of method of carbon arylation tandem reaction synthesizing heterocyclic compound of the photoinduction without metal catalytic, comprising the following steps: using formula III compound represented and formula IV compound represented as substrate, in organic solvent, under photosensitizer and alkali compounds effect, at room temperature in daylight, stir 24-48 hours, quenching reaction, extraction is washed, dry, concentration, purifying obtain heterocyclic compound shown in Formulas I or Formula II.The present invention reacts under light at room temperature photograph, no metal catalytic, compared with traditional Ullmann-Hurtley is coupled ring closure reaction, without adding catalyst, need to only react at room temperature, energy consumption is low, while also greatly reducing the generation of side reaction, environmentally protective.
Description
Technical field
The invention belongs to technical field of organic synthesis, are related to photoinduction and synthesize without the carbon arylation tandem reaction of metal catalytic
The method of heterocyclic compound, and in particular to photoinduction synthesizes isobioquin group chemical combination without the carbon arylation tandem reaction of metal catalytic
The method of object and isocoumarin class compound.
Background technique
Ullmann reaction is the cross-coupling reaction under copper catalytic condition, in the coupling of numerous transition metal-catalyzed participations
Reaction is compared, and Ullmann is reacted due to having used cheap and bottom poison copper reagent, is had in economic, environmental protection angle
Very big advantage.Researcher's discovery, Ullmann reacts the formation that can be applied not only to C-C, C-N, C-O key, and can promote
To the formation of C-S, C-P and C-Se key, so that having widened Ullmann reacts the application range in organic synthesis.Ullmann is anti-
Should be mostly all using in catalysed reaction of copper, ligand and alkali play an important role, and the reaction that ligand can increase copper catalyst is living
Property and selectivity.
Isocoumarin class compound is a kind of natural lactone compound being widely present in nature, have antibacterial,
The physiology such as anti-inflammatory, protease inhibition, weeding and anticancer and bioactivity (such as Urolithin A), basic parent nucleus are benzos six
First lactonic ring.Since isocoumarin class compound has anticancer activity, synthetic method always is the hot spot in organic synthesis.
Xi seminar in 2012 by CuI be catalyzed 2- Bromophenacyl amine compound or N- substitution -2- Bromophenacyl amine compound with
1,3- cyclohexadione compounds, under the conditions of high temperature of 120 DEG C, DMF is solvent, K3PO4For alkali, it can get 3- and isocoumarin replaced to spread out
Biology.When being substrate with asymmetry 1,3- dione compounds, good regioselectivity is shown, however yield is lower, only
Suitable for the 2- Bromophenacyl amine compound containing donor residues.2012, Yao seminar reported copper catalysis series connection C-C/C-
O coupling cyclisation, a kind of novel synthesis of rapid synthesis different coumarin derivative.This method is with the iodo- N- phenylbenzamaide of 2-
It is substrate with 1,3- cyclohexadione compounds, CuI is catalyst, and DMSO is solvent, Cs2CO3For alkali, under the conditions of 100 DEG C, 5-60min
The 3- that can be obtained medium yield on the upper side afterwards replaces different coumarin derivative.When using asymmetrical 1,3- dione compounds as substrate
When, it can get the product of isomers；With symmetrical 1,3- dione compounds be substrate when, can get single target product；When
When to replace -1,3- dione compounds or beta-ketoester be substrate with 2-, there is no corresponding product.Therefore, this method is only
There is good universality to symmetrical 1,3- dione compounds.
Compound of isobioquin group is also important chemical intermediate, such as tetrahydroisoquinoline ketone prepared therefrom derives
Object is applied not only to manufacture efficient pesticides, colour motion picture films and dyestuff etc., also has important pharmacological action, and such as anti-hypertension resists
Arrhythmia cordis, antithrombotic acitivity etc., while being also the important intermediate of gastric ulcer resistance medicine.In recent years, the isoquinolines of report and
The method of its derivative, reaction condition is often harsher, and yield is not also high, and by-product is more, purification difficult, some methods
Expensive catalyst must be used.
For the preparation method of both the above heterocycle compound there is still a need for Cu catalyst, reaction temperature is higher, and every kind of reaction
Chemo-selective it is poor, a kind of product can only be synthesized.Therefore, it is mild to develop a kind of reaction condition, environmentally protective, chemistry selection
The high new method of property seem very it is necessary to.
Summary of the invention
A kind of carbon arylation tandem reaction synthesizing heterocyclic the purpose of the present invention is to provide photoinduction without metal catalytic
The method for closing object is reacted under light at room temperature photograph, and no metal catalytic, energy consumption is low, while also greatly reducing the hair of side reaction
It is raw, it is environmentally protective.
To achieve the above object, the invention adopts the following technical scheme:
The method of carbon arylation tandem reaction synthesizing heterocyclic compound of the photoinduction without metal catalytic, comprising the following steps: with formula
III compound represented and formula IV compound represented are substrate, in organic solvent, are acted in photosensitizer and alkali compounds
Under, at room temperature in daylight, stir 24-48 hour, quenching reaction, extract, wash, dry, concentration, purify obtain Formulas I or
Heterocyclic compound shown in Formula II；
Wherein, R in formula III1Any one in hydrogen atom, alkyl, alkoxy, halogen atom or nitro, R2Selected from hydrogen original
Son, any one in alkyl or aryl, X is selected from I, Br or Cl；
R in formula IV3And R4Selected from alkyl, R5Any one in hydrogen atom, alkyl or aryl；
R in Formulas I and Formula II1、R3The same formula III of definition；R in Formulas I4The same formula IV of definition；R in Formula II5The same formula IV of definition.
Further, the molar ratio of the formula III compound represented, formula IV compound represented and alkali compounds is
1:3:2.
Further, the organic solvent is any in DMSO, acetonitrile, toluene, Isosorbide-5-Nitrae-dioxane, methanol or DMF
It is a kind of.
Further, the photosensitizer is selected from I2、Ru[bpy]3Cl2, Eosin Y, fluorescein, methylene blue, tetraphenyl porphin
Any one in quinoline, brave red or Eosin B, the molar ratio of photosensitizer and formula III compound represented is 1:(0.05 ~ 0.20).
Further, the alkali compounds is cesium carbonate, tripotassium phosphate, potassium carbonate, tert-butyl alcohol lithium, sodium tert-butoxide or uncle
Any one in butanol potassium.
Further, the illumination condition be wavelength be 365nm ultraviolet light, wavelength be 310nm ultraviolet light, wavelength be
Any one in the ultraviolet light of 254nm, incandescent light, xenon lamp, LED green light light, LED blue lamp light or LED red signal light.
Compared with prior art, the beneficial effects of the present invention are:
1. the carbon arylation tandem reaction that the present invention uses reacts, no metal catalytic, with traditional Ullmann under light at room temperature photograph
Coupling ring closure reaction is compared, and without adding catalyst, need to only be reacted at room temperature, energy consumption is low, while also subtracting significantly
Lack the generation of side reaction, it is environmentally protective.
2. the carbon arylation tandem reaction that the present invention uses photocatalytically can controllably be closed with different substrates
At the compound of isobioquin group or isocoumarin class compound of a series of different substituents, preferable chemistry selection is embodied
Property；When using asymmetrical beta-diketon as substrate, and R3Substituent group is less than R4When substituent group, isobioquin group is optionally synthesized
Compound embodies good regioselectivity；When there be big steric group (such as aryl) in the position the α of substrate beta-diketon, can also send out
Raw reaction, obtains isocoumarin class compound.
Specific embodiment
The following examples are intended to illustrate the invention, but is not used to limit the scope of protection of the present invention.Unless otherwise specified, real
Apply the conventional means that technological means used in example is well known to those skilled in the art.Test method in following embodiments, such as
It is conventional method without special instruction.
The organic solvent DMSO(dimethyl sulfoxide used in following embodiments), acetonitrile, DMF(dimethylformamide), first
Benzene, Isosorbide-5-Nitrae-dioxane or methanol are handled through anhydrous and oxygen-free using preceding.
Heterocyclic compound shown in Formulas I is compound of isobioquin group, heterocyclic compound isocoumarin class shown in Formula II
Compound, the reaction equation for synthesizing two class compounds are as follows:
,
。
- 1 (2H) -one of one 4- acetyl group -3- methylisoquinolinium of embodiment
By bromophenyl formamide (0.5mmol, 100mg) (X=Br, R in formula III1=R2=H), acetylacetone,2,4-pentanedione (1.5mmol, 154 μ
L) (R in formula IV3=R4=CH3, R5=H), Cs2CO3(1mmol, 326mg), Eosin Y (0.025mmol, 17.3mg), DMSO
(2.5mL) is added in crystal reaction tube, and mixture stirs under the conditions of room temperature 254nm ultraviolet light under the conditions of nitrogen atmosphere
36 hours, reaction was monitored by TLC.After completion of the reaction, reaction solution is cooled to room temperature, reaction is quenched with water, and use acetic acid
Ethyl ester (3 × 10mL) extraction.Combined organic extract is washed with brine, and is dried over sodium sulfate, filtering, and is concentrated in vacuo.It will
Residue is purified by silica gel column chromatography (petrol ether/ethyl acetate=2:1), obtains white solid product 90mg, yield
90%。
The nuclear-magnetism of -1 (2H) -one of 4- acetyl group -3- methylisoquinolinium is characterized as below:1H NMR (400 MHz, DMSO-d 6)
δ 11.50 (s, 1H), 8.30-8.09 (m, 1H), 7.80-7.61 (m, 1H), 7.48 (t, J = 7.8 Hz,
2H), 2.52 (s, 3H), 2.24 (s, 3H). 13C NMR (100 MHz, DMSO) δ 203.3, 162.1,
138.0, 135.1, 133.3, 127.4, 126.6, 124.5, 124.0, 117.20, 33.00, 17.70. ESI-MS
[M+H]+ m/z 202.18。
- 1 (2H) -one of two 4- acetyl group -3- methyl -7- nitroisoquinoline of embodiment
By 5- nitro bromophenyl formamide (0.5mmol, 122.5mg) (X=Br, R in formula III1=NO2, R2=H), acetylacetone,2,4-pentanedione
(1.5mmol, 154 μ L) (R in formula IV3=R4=CH3, R5=H), Cs2CO3(1mmol, 326mg), Eosin B (0.025mmol,
15.6mg), DMF(2.5mL) it is added in crystal reaction tube, mixture is under the conditions of nitrogen atmosphere, room temperature 254nm ultraviolet light
Under the conditions of stir 36 hours, reaction by TLC monitoring.After completion of the reaction, reaction solution is cooled to room temperature, is quenched with water anti-
It answers, and is extracted with ethyl acetate (3 × 10mL).Combined organic extract is washed with brine, and is dried over sodium sulfate, filtering, and
Vacuum concentration.Residue is purified by silica gel column chromatography (petrol ether/ethyl acetate=2:1), obtains yellow solid production
Object 117mg, yield 95%.
The nuclear-magnetism of -1 (2H) -one of 4- acetyl group -3- methyl -7- nitroisoquinoline is characterized as below:1H NMR (400 MHz,
DMSO-d 6) δ 12.01 (s, 1H), 8.88 (d, J = 2.6 Hz, 1H), 8.44-8.40 (m, 1H), 7.73
(d, J = 9.0 Hz, 1H), 2.57 (s, 3H), 2.33 (s, 3H). 13C NMR (100 MHz, DMSO) δ
202.5, 161.3, 145.1, 143.3, 139.8, 127.1, 125.9, 124.3, 123.2, 116.9, 33.0,
18.3. ESI-MS [M+H]+ m/z 247.13。
- 1 (2H) -one of three 4- acetyl group -3- cyclopropyl isoquinolin of embodiment
By bromophenyl formamide (0.5mmol, 100mg) (X=Br, R in formula III1=R2=H), 1- cyclopropyl -1,3- diacetyl
(1.5mmol, 172 μ L) (R in formula IV3=CH3, R4=cyclopropyl, R5=H),t- BuOLi(1mmol, 80.1mg), I2(0.1mmol,
25.4mg), toluene (2.5mL) is added in crystal reaction tube, and mixture is under the conditions of nitrogen atmosphere, under room temperature xenon lamp irradiation condition
Stirring 36 hours, reaction are monitored by TLC.After completion of the reaction, reaction solution is cooled to room temperature, reaction is quenched with water, is used in combination
Ethyl acetate (3 × 10mL) extraction.Combined organic extract is washed with brine, and is dried over sodium sulfate, filtering, and vacuum is dense
Contracting.Residue is purified by silica gel column chromatography (petrol ether/ethyl acetate=2:1), obtains white solid product
89mg, yield 78%.
The nuclear-magnetism of -1 (2H) -one of 4- acetyl group -3- cyclopropyl isoquinolin is characterized as below:1H NMR (400 MHz, DMSO-d 6) δ 11.56 (s, 1H), 8.24-8.18 (m, 1H), 7.75-7.68 (m, 1H), 7.56 (d, J = 8.2
Hz, 1H), 7.53-7.45 (m, 1H), 2.40-2.32 (m, 1H), 2.28 (s, 3H), 1.19-1.13 (m,
2H), 1.13-1.07 (m, 2H). 13C NMR (100 MHz, DMSO) δ 204.6, 162.1, 138.6, 135.4,
133.3, 127.4, 126.6, 124.5, 124.1, 117.1, 24.1, 17.9, 13.2. ESI-MS [M+H]+ m/z
228.19。
Example IV 7- ethyl -8- propiono -1,6- naphthyridines -5(6H) -one
By 2- chloropicolinamide (0.5mmol, 78mg) (X=Cl, R in formula III1=R2=H), 3,5- heptadione (1.5mmol,
213.7 μ L) (R in formula IV3=R4=ethyl, R5=H),t- BuONa(1mmol, 96.1mg), fluorescein (0.025mmol, 8.3mg),
MeOH(2.5mL it) is added in crystal reaction tube, mixture stirs under the conditions of room temperature blue LED illumination under the conditions of nitrogen atmosphere
36 hours, reaction was monitored by TLC.After completion of the reaction, reaction solution is cooled to room temperature, reaction is quenched with water, and use acetic acid
Ethyl ester (3 × 10mL) extraction.Combined organic extract is washed with brine, and is dried over sodium sulfate, filtering, and is concentrated in vacuo.It will
Residue is purified by silica gel column chromatography (petrol ether/ethyl acetate=2:1), obtains white solid product 81mg, yield
70%。
7- ethyl -8- propiono -1,6- naphthyridines -5(6H) nuclear-magnetism of -one is characterized as below:1H NMR (400 MHz,
DMSO-d 6) δ 11.78 (s, 1H), 8.94-8.87 (m, 1H), 8.53-8.46 (m, 1H), 7.53-7.48 (m,
1H), 2.97-2.90 (m, 2H), 2.50-2.42 (m, 2H), 1.20 (t, J = 7.5 Hz, 3H), 1.09 (t,J = 7.3 Hz, 3H). 13C NMR (100 MHz, DMSO) δ 206.0, 162.5, 154.8, 152.8, 147.0,
135.7, 122.0, 120.0, 117.9, 38.4, 24.7, 14.8, 8.7. ESI-MS [M+H]+ m/z 231.15。
Five 3- methyl isocoumarin of embodiment
By N- propyl bromophenyl formamide (0.5mmol, 121mg) (X=Br, R in formula III1=H, R2=n-propyl), acetylacetone,2,4-pentanedione
(1.5mmol, 154 μ L) (R in formula IV3=R4=CH3, R5=H), Cs2CO3(1mmol, 326mg), Eosin Y (0.025mmol,
17.3mg), DMSO(2.5mL) it is added in crystal reaction tube, mixture is under the conditions of nitrogen atmosphere, the irradiation of room temperature green LED light
Under the conditions of stir 36 hours, reaction by TLC monitoring.After completion of the reaction, reaction solution is cooled to room temperature, is quenched with water anti-
It answers, and is extracted with ethyl acetate (3 × 10mL).Combined organic extract is washed with brine, and is dried over sodium sulfate, filtering, and
Vacuum concentration.Residue is purified by silica gel column chromatography (petrol ether/ethyl acetate=8:1), obtains white solid production
Object 60mg, yield 75%.
The nuclear-magnetism of 3- methyl isocoumarin is characterized as below:1H NMR (400 MHz, CDCl3) δ 8.32-8.19 (m,
1H), 7.74-7.60 (m, 1H), 7.51-7.41 (m, 1H), 7.34 (d, J = 7.9 Hz, 1H), 6.26 (t,J = 1.0 Hz, 1H), 2.29 (d, J = 0.9 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ 158.2,
149.8, 132.9, 130.0, 124.8, 122.8, 120.1, 115.2, 98. 8, 14.9. ESI-MS [M+H]+ m/ z 161.20。
Six 3,4- dimethyl isocoumarin of embodiment
By N- phenyl neighbour iodobenzamide (0.5mmol, 161.5mg) (X=I, R in formula III1=H, R2=Ph), 3- methyl -2,4-
Pentanedione (1.5mmol, 175 μ L) (R in formula IV3=R4=CH3, R5=CH3), Cs2CO3(1mmol, 326mg), Eosin Y
(0.025mmol, 17.3mg), Isosorbide-5-Nitrae-dioxane (2.5mL) are added in crystal reaction tube, and mixture is in nitrogen atmosphere condition
Under, it is stirred 36 hours under the conditions of room temperature 310nm ultraviolet light, reaction is monitored by TLC.After completion of the reaction, by reaction solution
It is cooled to room temperature, reaction is quenched with water, and extracted with ethyl acetate (3 × 10mL).Combined organic extract is washed with brine,
It is dried over sodium sulfate, filters, and be concentrated in vacuo.By residue by silica gel column chromatography (petrol ether/ethyl acetate=8:1) into
Row purifying, obtains white solid product 61mg, yield 70%.
The nuclear-magnetism of 3,4- dimethyl isocoumarin is characterized as below:1H NMR (400 MHz, CDCl3) δ 8.33-8.27
(m, 1H), 7.76-7.71 (m, 1H), 7.52-7.44 (m, 2H), 2.32 (s, 3H), 2.18 (s, 3H). 13C
NMR (100 MHz, CDCl3) δ 162.9, 150.1, 138.7, 134.6, 129. 7, 127.1, 122.4, 120.
5, 107.7, 17.3, 12.2. ESI-MS [M+H]+ m/z 175.19。
Seven 3- methyl 4-phenyl isocoumarin of embodiment
By N- phenyl neighbour iodobenzamide (0.5mmol, 161.5mg) (X=I, R in formula III1=H, R2=Ph), 3- phenyl -2,4-
Pentanedione (1.5mmol, 264.3mg) (R in formula IV3=R4=CH3, R5=Ph), Cs2CO3(1mmol, 326mg), tiger are red
(0.025mmol, 25.5mg), DMSO(2.5mL) it is added in crystal reaction tube, for mixture under the conditions of nitrogen atmosphere, room temperature is red
It is stirred 36 hours under the conditions of color LED illumination, reaction is monitored by TLC.After completion of the reaction, reaction solution is cooled to room temperature, is used
Water quenching reaction, and extracted with ethyl acetate (3 × 10mL).Combined organic extract is washed with brine, and is dried over sodium sulfate,
Filtering, and be concentrated in vacuo.Residue is purified by silica gel column chromatography (petrol ether/ethyl acetate=8:1), is obtained white
Color solid product 71mg, yield 60%.
- 1 (2H) -one of eight 4- acetyl group -3- methylisoquinolinium of embodiment
By bromophenyl formamide (0.5mmol, 100mg) (X=Br, R in formula III1=R2=H), acetylacetone,2,4-pentanedione (1.5mmol, 154 μ
L) (R in formula IV3=R4=CH3, R5=H), Cs2CO3(1mmol, 326mg), Eosin B (0.025mmol, 15.6mg), DMSO
(2.5mL) is added in crystal reaction tube, and mixture stirs under the conditions of room temperature 365nm ultraviolet light under the conditions of nitrogen atmosphere
36 hours, reaction was monitored by TLC.After completion of the reaction, reaction solution is cooled to room temperature, reaction is quenched with water, and use acetic acid
Ethyl ester (3 × 10mL) extraction.Combined organic extract is washed with brine, and is dried over sodium sulfate, filtering, and is concentrated in vacuo.It will
Residue is purified by silica gel column chromatography (petrol ether/ethyl acetate=2:1), obtains white solid product 85mg, yield
85%。
- 1 (2H) -one of nine 4- acetyl group -3- methylisoquinolinium of embodiment
By bromophenyl formamide (0.5mmol, 100mg) (X=Br, R in formula III1=R2=H), acetylacetone,2,4-pentanedione (1.5mmol, 154 μ
L) (R in formula IV3=R4=CH3, R5=H), Cs2CO3(1mmol, 326mg), I2(0.1mmol, 25.4mg), DMSO(2.5mL) it is added
In crystal reaction tube, mixture stirs 36 hours under the conditions of room temperature 254nm ultraviolet light under the conditions of nitrogen atmosphere, reaction
It is monitored by TLC.After completion of the reaction, reaction solution is cooled to room temperature, is quenched with water reaction, and with ethyl acetate (3 ×
10mL) extract.Combined organic extract is washed with brine, and is dried over sodium sulfate, filtering, and is concentrated in vacuo.Residue is led to
It crosses silica gel column chromatography (petrol ether/ethyl acetate=2:1) to be purified, obtains white solid product 88mg, yield 88%.
- 1 (2H) -one of ten 4- acetyl group -3- methylisoquinolinium of embodiment
By bromophenyl formamide (0.5mmol, 100mg) (X=Br, R in formula III1=R2=H), acetylacetone,2,4-pentanedione (1.5mmol, 154 μ
L) (R in formula IV3=R4=CH3, R5=H),t- BuOK(1mmol, 112.2mg), methylene blue (0.025mmol, 9.3mg), DMSO
(2.5mL) is added in crystal reaction tube, and it is small that mixture stirs 48 under the conditions of nitrogen atmosphere, under room temperature incandescent light irradiation condition
When, reaction is monitored by TLC.After completion of the reaction, reaction solution is cooled to room temperature, reaction is quenched with water, and use ethyl acetate
(3 × 10mL) extraction.Combined organic extract is washed with brine, and is dried over sodium sulfate, filtering, and is concentrated in vacuo.It will be remaining
Object is purified by silica gel column chromatography (petrol ether/ethyl acetate=2:1), obtains white solid product 70mg, yield 70%.
- 1 (2H) -one of 11 4- acetyl group -3- methylisoquinolinium of embodiment
By bromophenyl formamide (0.5mmol, 100mg) (X=Br, R in formula III1=R2=H), acetylacetone,2,4-pentanedione (1.5mmol, 154 μ
L) (R in formula IV3=R4=CH3, R5=H), Cs2CO3(1mmol, 326mg), tetraphenylporphyrin (0.025mmol, 15.4mg), DMSO
(2.5mL) is added in crystal reaction tube, and mixture stirs under the conditions of room temperature 365nm ultraviolet light under the conditions of nitrogen atmosphere
24 hours, reaction was monitored by TLC.After completion of the reaction, reaction solution is cooled to room temperature, reaction is quenched with water, and use acetic acid
Ethyl ester (3 × 10mL) extraction.Combined organic extract is washed with brine, and is dried over sodium sulfate, filtering, and is concentrated in vacuo.It will
Residue is purified by silica gel column chromatography (petrol ether/ethyl acetate=2:1), obtains white solid product 65mg, yield
65%。
- 1 (2H) -one of 12 4- acetyl group -3- methylisoquinolinium of embodiment
By bromophenyl formamide (0.5mmol, 100mg) (X=Br, R in formula III1=R2=H), acetylacetone,2,4-pentanedione (1.5mmol, 154 μ
L) (R in formula IV3=R4=CH3, R5=H), K3PO4(1mmol, 212mg), Ru [bpy]3Cl2(0.025mmol, 18.7mg), DMSO
(2.5mL) is added in crystal reaction tube, and mixture stirs under the conditions of room temperature 254nm ultraviolet light under the conditions of nitrogen atmosphere
24 hours, reaction was monitored by TLC.After completion of the reaction, reaction solution is cooled to room temperature, reaction is quenched with water, and use acetic acid
Ethyl ester (3 × 10mL) extraction.Combined organic extract is washed with brine, and is dried over sodium sulfate, filtering, and is concentrated in vacuo.It will
Residue is purified by silica gel column chromatography (petrol ether/ethyl acetate=2:1), obtains white solid product 60mg, yield
60%。
- 1 (2H) -one of 13 4- acetyl group -3- methylisoquinolinium of embodiment
By bromophenyl formamide (0.5mmol, 100mg) (X=Br, R in formula III1=R2=H), acetylacetone,2,4-pentanedione (1.5mmol, 154 μ
L) (R in formula IV3=R4=CH3, R5=H), Cs2CO3(1mmol, 326mg), Eosin Y (0.025mmol, 17.3mg), DMSO
(2.5mL) is added in crystal reaction tube, and mixture stirs under the conditions of room temperature 254nm ultraviolet light under the conditions of nitrogen atmosphere
48 hours, reaction was monitored by TLC.After completion of the reaction, reaction solution is cooled to room temperature, reaction is quenched with water, and use acetic acid
Ethyl ester (3 × 10mL) extraction.Combined organic extract is washed with brine, and is dried over sodium sulfate, filtering, and is concentrated in vacuo.It will
Residue is purified by silica gel column chromatography (petrol ether/ethyl acetate=2:1), obtains white solid product 90mg, yield
90%。
- 1 (2H) -one of 14 4- acetyl group -3- methylisoquinolinium of embodiment
By bromophenyl formamide (0.5mmol, 100mg) (X=Br, R in formula III1=R2=H), acetylacetone,2,4-pentanedione (1.5mmol, 154 μ
L) (R in formula IV3=R4=CH3, R5=H), Cs2CO3(1mmol, 326mg), Eosin Y (0.025mmol, 17.3mg), MeCN
(2.5mL) is added in crystal reaction tube, and mixture stirs under the conditions of room temperature 254nm ultraviolet light under the conditions of nitrogen atmosphere
24 hours, reaction was monitored by TLC.After completion of the reaction, reaction solution is cooled to room temperature, reaction is quenched with water, and use acetic acid
Ethyl ester (3 × 10mL) extraction.Combined organic extract is washed with brine, and is dried over sodium sulfate, filtering, and is concentrated in vacuo.It will
Residue is purified by silica gel column chromatography (petrol ether/ethyl acetate=2:1), obtains white solid product 60mg, yield
60%。
- 1 (2H) -one of 15 4- acetyl group -3- methylisoquinolinium of embodiment
By bromophenyl formamide (0.5mmol, 100mg) (X=Br, R in formula III1=R2=H), acetylacetone,2,4-pentanedione (1.5mmol, 154 μ
L) (R in formula IV3=R4=CH3, R5=H), potassium carbonate (1mmol, 138.2mg), Eosin Y (0.025mmol, 17.3mg), DMSO
(2.5mL) is added in crystal reaction tube, and mixture stirs under the conditions of room temperature 254nm ultraviolet light under the conditions of nitrogen atmosphere
24 hours, reaction was monitored by TLC.After completion of the reaction, reaction solution is cooled to room temperature, reaction is quenched with water, and use acetic acid
Ethyl ester (3 × 10mL) extraction.Combined organic extract is washed with brine, and is dried over sodium sulfate, filtering, and is concentrated in vacuo.It will
Residue is purified by silica gel column chromatography (petrol ether/ethyl acetate=2:1), obtains white solid product 70mg, yield
70%。
The embodiment of the above, only presently preferred embodiments of the present invention, is only used to explain the present invention, not limit
The scope of the present invention processed to those of ordinary skill in the art certainly can be according to skill disclosed in this specification
Art content makes other embodiments easily by way of replacing or changing, therefore all made in the principle of the present invention
Changes and improvements etc., should be included in scope of the present invention patent.
Claims (6)
1. the method for carbon arylation tandem reaction synthesizing heterocyclic compound of the photoinduction without metal catalytic, which is characterized in that including
Following steps: using formula III compound represented and formula IV compound represented as substrate, in organic solvent, in photosensitizer and
Under alkali compounds effect, at room temperature in daylight, stirs 24-48 hours, quenching reaction, extract, wash, dry, concentration,
Purifying obtains heterocyclic compound shown in Formulas I or Formula II；
Wherein, R in formula III1Any one in hydrogen atom, alkyl, alkoxy, halogen atom or nitro, R2Selected from hydrogen original
Son, any one in alkyl or aryl, X is selected from I, Br or Cl；
R in formula IV3And R4Selected from alkyl, R5Any one in hydrogen atom, alkyl or aryl；
R in Formulas I and Formula II1、R3The same formula III of definition；R in Formulas I4The same formula IV of definition；R in Formula II5The same formula IV of definition.
2. the side of carbon arylation tandem reaction synthesizing heterocyclic compound of the photoinduction according to claim 1 without metal catalytic
Method, which is characterized in that the molar ratio of the formula III compound represented, formula IV compound represented and alkali compounds is 1:
3:2.
3. the side of carbon arylation tandem reaction synthesizing heterocyclic compound of the photoinduction according to claim 1 without metal catalytic
Method, which is characterized in that the organic solvent is any one in DMSO, acetonitrile, toluene, Isosorbide-5-Nitrae-dioxane, methanol or DMF
Kind.
4. the side of the carbon arylation tandem reaction synthesizing heterocyclic compound according to photoinduction described in claim 1 without metal catalytic
Method, which is characterized in that the photosensitizer is selected from I2、Ru[bpy]3Cl2, Eosin Y, fluorescein, methylene blue, tetraphenylporphyrin, tiger
The molar ratio of any one in red or Eosin B, photosensitizer and formula III compound represented is (0.05 ~ 0.20): 1.
5. the side of the carbon arylation tandem reaction synthesizing heterocyclic compound according to photoinduction described in claim 1 without metal catalytic
Method, which is characterized in that the alkali compounds is cesium carbonate, tripotassium phosphate, potassium carbonate, tert-butyl alcohol lithium, sodium tert-butoxide or tertiary fourth
Any one in potassium alcoholate.
6. the side of the carbon arylation tandem reaction synthesizing heterocyclic compound according to photoinduction described in claim 1 without metal catalytic
Method, which is characterized in that the illumination condition be wavelength be 365nm ultraviolet light, wavelength be 310nm ultraviolet light, wavelength be
Any one in the ultraviolet light of 254nm, incandescent light, xenon lamp, LED green light light, LED blue lamp light or LED red signal light.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810885686.5A CN108947900B (en) | 2018-08-06 | 2018-08-06 | Method for synthesizing heterocyclic compound by photoinduced metal-free catalyzed carbon arylation cascade reaction |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810885686.5A CN108947900B (en) | 2018-08-06 | 2018-08-06 | Method for synthesizing heterocyclic compound by photoinduced metal-free catalyzed carbon arylation cascade reaction |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN108947900A true CN108947900A (en) | 2018-12-07 |
| CN108947900B CN108947900B (en) | 2021-07-30 |
Family
ID=64467652
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201810885686.5A Active CN108947900B (en) | 2018-08-06 | 2018-08-06 | Method for synthesizing heterocyclic compound by photoinduced metal-free catalyzed carbon arylation cascade reaction |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN108947900B (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110845404A (en) * | 2019-12-05 | 2020-02-28 | 哈尔滨工业大学 | Preparation method of 2-phenyl substituted pyridine nitrogen oxide compound |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102382051A (en) * | 2011-09-13 | 2012-03-21 | 清华大学 | Method for preparing isoquinoline ketone and derivatives thereof |
| CN105153030A (en) * | 2015-10-14 | 2015-12-16 | 吉首大学 | Perfluoro group substituted isoquinoline-1,3(2H,4H)-diketone as well as preparation method and application thereof |
| CN107531589A (en) * | 2015-01-23 | 2018-01-02 | Gvk生物科技私人有限公司 | Trka kinase inhibitors |
-
2018
- 2018-08-06 CN CN201810885686.5A patent/CN108947900B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102382051A (en) * | 2011-09-13 | 2012-03-21 | 清华大学 | Method for preparing isoquinoline ketone and derivatives thereof |
| CN107531589A (en) * | 2015-01-23 | 2018-01-02 | Gvk生物科技私人有限公司 | Trka kinase inhibitors |
| CN105153030A (en) * | 2015-10-14 | 2015-12-16 | 吉首大学 | Perfluoro group substituted isoquinoline-1,3(2H,4H)-diketone as well as preparation method and application thereof |
Non-Patent Citations (7)
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110845404A (en) * | 2019-12-05 | 2020-02-28 | 哈尔滨工业大学 | Preparation method of 2-phenyl substituted pyridine nitrogen oxide compound |
| CN110845404B (en) * | 2019-12-05 | 2022-03-04 | 哈尔滨工业大学 | Preparation method of 2-phenyl substituted pyridine nitrogen oxide compound |
Also Published As
| Publication number | Publication date |
|---|---|
| CN108947900B (en) | 2021-07-30 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN109988117B (en) | Preparation method of 3-methylquinoxaline-2 (1H) -ketone derivatives | |
| CN111675712B (en) | Synthesis method of pyrazolone benzodiazepine compound | |
| CN106905284B (en) | A kind of catalysis oxidation synthetic method of miscellaneous anthracene ketone compounds | |
| CN108164475B (en) | Method for catalytic synthesis of difluoromethyl-substituted linear aryl hetero-ketone | |
| CN108947900A (en) | The method of carbon arylation tandem reaction synthesizing heterocyclic compound of the photoinduction without metal catalytic | |
| CN110590788B (en) | 2-acyl-9H-pyrrolo [1,2-a]Synthesis method of indole compound | |
| CN102863399B (en) | Synthetic method for isatoic anhydride derivative | |
| CN109336753B (en) | Synthetic method of alpha-benzyl substituted 1, 3-diketone compound | |
| CN114716438B (en) | Benzo [7,8] indolizine [1,2-c ] quinoline skeleton derivative and synthetic method thereof | |
| CN109651385A (en) | A kind of preparation method of pyrans [3,2-a] carbazole compound | |
| CN113444041B (en) | Method for synthesizing polysubstituted quinoline compound by photocatalysis | |
| CN113045530B (en) | Method for preparing naphthopyran compounds by ruthenium catalysis | |
| CN115322100A (en) | Delta, epsilon-alkenyl ketone compound and preparation method and application thereof | |
| CN108164483A (en) | A kind of five yuan of new heteroaromatics and aromatic ring and five yuan of heteroaromatic arylation synthetic methods | |
| CN111777564B (en) | Method for synthesizing quinazolinone compound by photocatalytic alcohol oxidation in aqueous phase | |
| CN110698483B (en) | Synthesis of 2-sulfonyl-9H-pyrrolo [1,2-a ] indole compound | |
| CN115536659B (en) | Preparation method of benzo [4,5] imidazo [1,2-A ] pyridine | |
| CN109776388B (en) | Synthetic method of indoline derivative with C2 quaternary carbon center | |
| CN113443974B (en) | Method for preparing phenanthrene derivative from biphenyl ketene | |
| CN114213370B (en) | Method for synthesizing alkylated electron-rich heterocyclic aromatic hydrocarbon by photo-induced NHPI ester decarboxylation coupling | |
| CN113636977B (en) | Synthesis method of 2-aryl benzazepine and derivatives thereof | |
| CN108383706A (en) | A kind of synthetic method of α-arone or α-heteroaryl ketone | |
| KR102628273B1 (en) | Method for synthesizing a tetrahydroquinoline derivative comprising an acetamide functional group and a tetrahydroquinoline derivative synthesized using the same | |
| CN113620795B (en) | Method for synthesizing benzocycloheptenone compounds | |
| CN112209867B (en) | Synthetic method of 2-alkynyl substituted indole compound |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |