CN106966973A - N phenyl N(The quinolyl of 2 methyl 8)The preparation method of benzamide - Google Patents
N phenyl N(The quinolyl of 2 methyl 8)The preparation method of benzamide Download PDFInfo
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- CN106966973A CN106966973A CN201710353245.6A CN201710353245A CN106966973A CN 106966973 A CN106966973 A CN 106966973A CN 201710353245 A CN201710353245 A CN 201710353245A CN 106966973 A CN106966973 A CN 106966973A
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- methyl
- benzamide
- quinolyls
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom 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 ring carbon atoms
- C07D215/38—Nitrogen atoms
- C07D215/40—Nitrogen atoms attached in position 8
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The present invention relates to a kind of preparation method of N phenyl N (quinolyl of 2 methyl 8) benzamide, successively add N (quinolyl of 2 methyl 8) benzamide, triphenyl bismuth, Salicylaldoxime, sodium acid carbonate, 1 in the reactor, 4 dioxane solvents and No. 5 magnetons one, will be placed in heating response in oil bath pan after condenser pipe from the bottom to top logical condensed water by reactor.Reaction pours into reaction solution in separatory funnel after terminating, plus distilled water, then is extracted with ethyl acetate 3 times.Merge gained organic phase, rotated evaporimeter is spin-dried for, and crude product isolates and purifies to obtain N phenyl N (quinolyl of 2 methyl 8) benzamide through column chromatography chromatogram, and yield is 93%.Reaction condition of the present invention is gentle, using cheap metal copper catalyst, nitrogen-less protection, it is not necessary to which oxidant is participated in, and economy is higher, environmentally friendly;Available to medicine, agricultural chemicals and materials synthesis field.
Description
Technical field
The present invention relates to the preparation method of transition metal-catalyzed synthesis aromatic amides class compound, and in particular to a kind of N-
The preparation method of phenyl-N- (2- methyl -8- quinolyls) benzamide.
Background technology
N- aryl compounds are widely used in the neck such as medicine, agricultural chemicals, materials synthesis and solar cell photoelectric converting material
Domain.The commonly used great interest for causing researchers of N- aryl class compounds, promoting the research in the field turns into
One of current study hotspot, while also making the synthesis of such compound and application obtain further deep development.
Since finding that aryl boric acid can carry out arylation reaction under copper catalysis since 1998, aryl boric acid and acid amides
Arylation reaction under the catalysis of mantoquita has obtained very big progress.He overcomes many deficiencies of Goldberg reactions, should
The conventional copper acetate monohydrate of reaction makees catalyst, can carry out under mild conditions.But aryl boric acid is general by corresponding virtue
Prepared by base halogen, this adds increased reactions steps, because its property is active, causes its purification, preserves difficult, this all limits
The application of aryl boric acid reagent.And not only yield is better than boric acid for the arylation reaction that triphenyl bismuth is participated in, and reaction condition is more
To be gentle.Because bismuth salt storage is stable in atmosphere, therefore its operation is easy.With green, change efficiently, economic
Be reacted to development trend instantly, and virtueization reagent is made using triphenyl bismuth, and synthesis aromatic amides class compound has important
Meaning.
The content of the invention
The purpose of the present invention is to be directed to above-mentioned present situation, it is desirable to provide a kind of reaction condition is gentle, cheap metal is catalyzed, atom
Economy is higher, yield is higher and the preparation side of environment amenable N- phenyl-N- (2- methyl -8- quinolyls) benzamide
Method.
The implementation of the object of the invention is, the preparation method of N- phenyl-N- (2- methyl -8- quinolyls) benzamide,
N- (2- methyl -8- quinolyls) benzamide, triphenyl bismuth, catalyst acetic anhydride are sequentially added in the reactor
Copper, sodium acid carbonate, Isosorbide-5-Nitrae-dioxane solvent and No. 5 magnetons one, condenser pipe is led to reactor after condensed water from the bottom to top
It is placed in heating response 12 hours in 100 DEG C of oil bath pans;Reaction solution is poured into separatory funnel, adds 15mL water, then use ethyl acetate
Extraction three times, each 10mL;Merge gained organic phase, rotated evaporimeter is spin-dried for, and crude product is isolated and purified through column chromatography chromatogram,
Obtain N- phenyl-N- (2- methyl -8- quinolyls) benzamide.,
The present invention is synthesized using N- (2- methyl -8- quinolyls) benzamides and triphenyl bismuth, and reaction condition is gentle, is used
Cheap metal copper catalyst, nitrogen-less protection, it is not necessary to which oxidant is participated in, and economy is higher, selectivity is high, yield is higher and
It is environmentally friendly.After testing, N- phenyl-N- (2- methyl -8- quinolyls) benzamide prepared using the present invention can be applied
To fields such as pharmaceutical synthesis, pesticide synthesis and coating Dyestuff synthesis.
Embodiment
The present invention is successively to add N- (2- methyl -8- quinolyls) benzamide, Salicylaldoxime, triphenyl in the reactor
Bismuth, sodium acid carbonate, Isosorbide-5-Nitrae-dioxane solvent and No. 5 magnetons one, condenser pipe is led to reactor after condensed water from the bottom to top
It is placed in heating response in oil bath pan.Reaction pours into reaction solution in separatory funnel after terminating, plus distilled water, then uses L ethyl acetate
Extraction 3 times.Merge gained organic phase, rotated evaporimeter is spin-dried for, and crude product isolates and purifies to obtain N- phenyl-N- through column chromatography chromatogram
(2- methyl -8- quinolyls) benzamide.
The purity of N- (2- methyl -8- quinolyls) benzamide is 98%, and triphenyl bismuth purity is 98%, anhydrous vinegar
The purity of sour copper is 99%, and the purity of sodium acid carbonate is 99.5%, and the purity of Isosorbide-5-Nitrae-dioxane is 99.5%.
Reactor is that lower end is spherical micro-reaction pipe.Condenser pipe puts micro-reaction pipe after leading to condensed water from the bottom to top
In 100 DEG C of silicone oil baths, the spherical depth being immersed in silicone oil in micro-reaction pipe lower end is that micro-reaction pipe lower end is spherical
The height of interior reaction solution.
The magnetic stirring apparatus rotating speed is 600 turns/s.
The present invention reaction expression be:
The present invention is described in detail with specific embodiment below.
0.2mmolN- (2- methyl -8- quinolyls) benzamide, 0.36mmol tri- are sequentially added in the reactor
Phenyl bismuth, 40mol% catalyst Salicylaldoxime, 0.4mmol sodium acid carbonates, 2mL 1,4- dioxane solvents and No. 5 magnetons
One, reactor will be placed in heating response 12 hours in 100 DEG C of oil bath pans after condenser pipe from the bottom to top logical condensed water;Reaction solution
Pour into separatory funnel, add 15mL water, then be extracted with ethyl acetate three times, each 10mL;Merge gained organic phase, it is rotated
Evaporimeter is spin-dried for, and crude product is isolated and purified through column chromatography chromatogram, obtains N- phenyl-N- (2- methyl -8- quinolyls) benzamides
Compound.
Rotary Evaporators are using ultrasonic Rotary Evaporators, High Temperature Rotating evaporimeter, as long as being spin-dried for.
Column chromatography method is, is first 200-300 mesh by granularity, aperture is 80-100A, and pore volume is 0.8-1.0mL/g, and PH is
6-7 neutral column chromatography silica gel, it is GG-17 to be loaded into the specification fixed in advance with iron stand, and volume is 100mL chromatography
Post, then by ethyl acetate/petroleum ether=1 configured:5, Rf=0.2 100mL solvents, pour into chromatographic column, allow column chromatography
Silica gel is fully swelled, and opens pillar switch, and the beaker that a 100mL is placed below in pillar collects solvent, and with pressure
The interface of the ball compacting pillar of power, adjustment solvent and silica gel, treats that silica gel is equal with solvent concave meniscus, closes pillar and open
Close, crude product is transferred in pillar (being that loading is operated) with glass dropper, completion of the sample is treated, the bedding one on crude product upper strata
Layer granularity is 40-70 mesh, and composition is SiO2Quartz sand, then the solvent collected in beaker is all poured into pillar, then open
Pillar is switched, and adjusts the pressure of ball, is collected the solvent at column outlet stream with 15mL test tube, is adjusted the stream of solvent
Speed is 2.5mL/min, with the solvent collected in TLC point plate test tubes, treats N- phenyl-N- (2- methyl -8- quinolyls) benzene
Carboxamide product occurs, and the test tube that will carry the solvent of N- phenyl-N- (2- methyl -8- quinolyls) benzamide product is whole
Collect, by vacuum distillation, remove solvent, produce N- phenyl-N- (2- methyl -8- quinolyls) benzamide net product
62.9mg, product is faint yellow solid, and yield is 93%.
Hydrogen nuclear magnetic resonance1HNMR(400MHz,CDCl3):δ2.66(s,3H),7.09–7.12(m,4H),7.18–7.25(m,
5H), 7.37-7.41 (m, 1H), 7.57-7.59 (m, 3H), 7.63-7.65 (m, 1H), 7.92 (d, J=8.24Hz, 1H);13C
NMR(100MHz,CDCl3):δ25.5,122.4,125.4,125.8,127.0,127.2,127.3,127.4,128.7,
128.8,128.9,129.6,135.8,137.1,141.2,143.7,144.7,159.3,172.0。
Claims (6)
- The preparation method of 1.N- phenyl-N- (2- methyl -8- quinolyls) benzamide, it is characterised in that:In the reactor by first Order adds N- (2- methyl -8- quinolyls) benzamide, triphenyl bismuth, catalyst Salicylaldoxime, sodium acid carbonate, 1,4- afterwards Reactor, is placed in 100 DEG C of oil bath pans by dioxane solvent and No. 5 magnetons one after condenser pipe is led into condensed water from the bottom to top Heating response 12 hours;Reaction solution is poured into separatory funnel, adds 15mL water, then be extracted with ethyl acetate three times, each 10mL; Merge gained organic phase, rotated evaporimeter is spin-dried for, and crude product is isolated and purified through column chromatography chromatogram, obtains N- phenyl-N- (2- first Base -8- quinolyls) benzamide.
- 2. the preparation method of N- phenyl-N- (2- methyl -8- quinolyls) benzamide according to claim 1, its feature It is:0.2mmol N- (2- methyl -8- quinolyls) benzamide, 0.36mmol triphens are sequentially added in the reactor Base bismuth, 40mol% catalyst Salicylaldoxime, 0.4mmol sodium acid carbonates, 2mL 1,4- dioxane solvents and No. 5 magnetons one It is individual, reactor will be placed in heating response 12 hours in 100 DEG C of oil bath pans after condenser pipe from the bottom to top logical condensed water;Reaction solution falls Enter in separatory funnel, add 15mL water, then be extracted with ethyl acetate three times, each 10mL;Merge gained organic phase, rotated steaming Hair instrument is spin-dried for, and crude product is isolated and purified through column chromatography chromatogram, obtains N- phenyl-N- (2- methyl -8- quinolyls) benzamide.
- 3. the preparation method of N- phenyl-N- (2- methyl -8- quinolyls) benzamide according to claim 1 or 2, it is special Levy and be:The purity of N- (2- methyl -8- quinolyls) benzamide is 98%, and triphenyl bismuth purity is 98%, anhydrous vinegar The purity of sour copper is 99%, and the purity of sodium acid carbonate is 99.5%, and the purity of Isosorbide-5-Nitrae-dioxane is 99.5%.
- 4. the preparation method of N- phenyl-N- (2- methyl -8- quinolyls) benzamide according to claim 1, its feature It is:Reactor is that lower end is spherical micro-reaction pipe.
- 5. the preparation method of N- phenyl-N- (2- methyl -8- quinolyls) benzamide according to claim 1 or 4, it is special Levy and be:Micro-reaction pipe is placed in 100 DEG C of silicone oil baths by condenser pipe after leading to condensed water from the bottom to top, micro-reaction pipe lower end The spherical depth being immersed in silicone oil is the height of the spherical interior reaction solution in micro-reaction pipe lower end.
- 6. the preparation method of N- phenyl-N- (2- methyl -8- quinolyls) benzamide according to claim 1, its feature It is:Magnetic stirring apparatus rotating speed is 600 turns/s.
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Cited By (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN113698338A (en) * | 2021-09-29 | 2021-11-26 | 湖北工业大学 | Preparation method of styrene double oxidation product |
CN113773250A (en) * | 2021-10-08 | 2021-12-10 | 湖北工业大学 | 5-cyano-8-acylaminoquinoline compound and preparation method thereof |
WO2022020261A1 (en) * | 2020-07-20 | 2022-01-27 | Neurodon Corporation | Quinolines that modulate serca and their use for treating disease |
US11730729B2 (en) | 2020-07-20 | 2023-08-22 | Neurodon Corporation | Quinolines that modulate SERCA and their use for treating disease |
US11827626B2 (en) | 2014-08-29 | 2023-11-28 | Neurodon Corporation | Quinolines that modulate SERCA and their use for treating disease |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN106496119A (en) * | 2016-10-17 | 2017-03-15 | 江南大学 | A kind of preparation method of 8 aminoquinoline of N phenyl |
-
2017
- 2017-05-18 CN CN201710353245.6A patent/CN106966973A/en active Pending
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN106496119A (en) * | 2016-10-17 | 2017-03-15 | 江南大学 | A kind of preparation method of 8 aminoquinoline of N phenyl |
Non-Patent Citations (4)
Title |
---|
B. D. JADHAV,等: "A facile and practical copper diacetate mediated,ligand free C–N cross coupling of trivalent organobismuth compounds with amines and N-heteroarenes", 《RSC ADVANCES》 * |
DOMINIC M. T. CHAN: "Promotion of Reaction of N-H Bonds with Triarylbismuth and Cupric Acetate", 《TETRAHEDRON LETTERS》 * |
OLGA TSUBRIK,等: "Arylation of diversely substituted hydrazines by tri- and pentavalent organobismuth reagents", 《TETRAHEDRON》 * |
PAVEL STARKOV,等: "Copper-catalyzed N-arylation of carbamate-protected hydrazones with organobismuthanes", 《TETRAHEDRON LETTERS》 * |
Cited By (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US11827626B2 (en) | 2014-08-29 | 2023-11-28 | Neurodon Corporation | Quinolines that modulate SERCA and their use for treating disease |
WO2022020261A1 (en) * | 2020-07-20 | 2022-01-27 | Neurodon Corporation | Quinolines that modulate serca and their use for treating disease |
US11730729B2 (en) | 2020-07-20 | 2023-08-22 | Neurodon Corporation | Quinolines that modulate SERCA and their use for treating disease |
US11890279B2 (en) | 2020-07-20 | 2024-02-06 | Neurodon Corporation | Quinolines that modulate SERCA and their use for treating disease |
US11992487B2 (en) | 2020-07-20 | 2024-05-28 | Neurodon Corporation | Quinolines that modulate SERCA and their use for treating disease |
CN113698338A (en) * | 2021-09-29 | 2021-11-26 | 湖北工业大学 | Preparation method of styrene double oxidation product |
CN113773250A (en) * | 2021-10-08 | 2021-12-10 | 湖北工业大学 | 5-cyano-8-acylaminoquinoline compound and preparation method thereof |
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Application publication date: 20170721 |