CN102408285B - Method for directly aminating benzyl hydrocarbon of methylbenzene derivative - Google Patents
Method for directly aminating benzyl hydrocarbon of methylbenzene derivative Download PDFInfo
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- CN102408285B CN102408285B CN2011102785440A CN201110278544A CN102408285B CN 102408285 B CN102408285 B CN 102408285B CN 2011102785440 A CN2011102785440 A CN 2011102785440A CN 201110278544 A CN201110278544 A CN 201110278544A CN 102408285 B CN102408285 B CN 102408285B
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Abstract
The invention belongs to the technical field of organic synthesis chemistry and discloses a method for directly aminating benzyl hydrocarbon of methylbenzene derivative by metal salt catalyst and animation regent N-fluorobenzenesulphonimide (NFSI). Series of benzylamine compounds are prepared. The invention overcomes the limitation of the current method for directly aminating benzyl hydrocarbon, realizes benzyl hydrocarbon amination reaction of only usage dose of methylbenzene and animation regent and synchronous amination reaction of two methyl of dimethylbenzene and derivative thereof for the first time, and realizes a breakthrough that primary carbon atom is superior to secondary carbon atom in benzyl hydrocarbon amination reaction selectivity. The amination reaction realized in the invention is simple to operate, high-efficiency and easy to obtain raw material, reagent and catalyst, and is suitable for synthesizing various benzylamine compounds and for large scale industrialization production.
Description
Technical field
The invention belongs to the technical field of Synthetic Organic Chemistry, relate to the hydrocarbon direct aminatin method of benzyl of metal catalytic toluene derivative and N-fluoro-diphenyl sulfimide (N-fluorobenzenesulfonimide-NFSI).
Background technology
Amine is the very important organic compound of a class, extensively is present in and has (R.Hili, A.K.Yudin in bioactive molecule, Nat.Chem.Biol.6,284, (2006) .T.Henkel, R.M.Brunne, H.M ü ller, F.Reichel, Angew.Chem., Int.Ed.38,643, (1999)).In addition, benzylamine or a kind of important organic synthesis intermediate, be widely used in the preparation of fuel, agricultural chemicals, medicine, novel material, artificial resin etc.Comprise from the main path of the most basic industrial chemicals toluene, the synthetic benzylamine of dimethylbenzene and benzyl diamine compounds at present: 1) toluene → halobenzene → benzylamine; 2) toluene → phenylformic acid → benzamide → cyanobenzene → benzylamine; 3) toluene → phenyl aldehyde → benzylamine.Undoubtedly, from the synthetic carbonnitrogen bond of hydrocarbon key, be directly method (F.Collet, R.H.Dodd, P.Dauban, Chem.Commun.5061 (2009)) the simplest, efficient synthesizing aminated compounds.The reaction of the direct aminatin of the hydrocarbon key of benzyl of highly selective is along with metal in recent years is the discovery in spring and obtained good development (H.M.L.Davies, J.R.Manning, Nature 451,417 (2008)), yet such reaction exists limitation for the most basic industrial chemicals toluene, the amination of dimethylbenzene.Because this class reaction is all to follow reaction preference (S.K.-Y.Leung, W.-M.Tsui, J.-S.Huang, C.-M.Che, J.-L.Liang, N.Zhu, J.Am.Chem.Soc.127,16629, (2005) that secondary carbon(atom) is better than primary carbon atom; M.R.Fructos .S.Trofimenko, M.M.
P.J.P é rez, J.Am.Chem.Soc.128,11784, (2006)), therefore, realize that primary carbon atom is better than the amination reaction selectivity difficulty of secondary carbon(atom).Usually, the hydrocarbon key amination reaction of benzyl methyl poor activity, the toluene direct aminatin of report reaction at present all need be used greatly excessive toluene (15 times to 500 times) (Huard, K.; Lebel, H.Chem.Eur.J.14,6222 (2008); S.Wiese, Y.M.Badiei, R.T.Gephart, S.Mossin, M.S.Varonka, M.M.Melzer, K.Meyer, T.R.Cundari, T.H.Warren, Angew.Chem., Int.Ed., 49,8850 (2010); D.A.Powell, H.Fan, J.Org.Chem.75,2726 (2010) .).Up to the present, only when the direct benzylamine reaction of the toluene of using dosage and amination reagent and two methyl of dimethylbenzene the direct aminatin reaction all unrealized.
Summary of the invention
The objective of the invention is the limitation for the hydrocarbon direct aminatin method of present existing benzyl, invent a kind of succinct, novel method efficiently of utilizing the hydrocarbon direct aminatin of benzyl that metal catalyst and amination reagent N-fluoro-diphenyl sulfimide realize toluene derivative, prepared serial benzylamine compound.Amination reaction when this method has realized the hydrocarbon amination reaction of benzyl of the toluene of using dosage only and derivative and amination reagent and two methyl of diformazan benzene and its derivative first, also realized that the benzyl hydrocarbon amination reaction that primary carbon atom is better than secondary carbon(atom) optionally breaks through.
Its reaction equation is as follows:
R
1For hydrogen atom, alkyl, aryl, heteroaryl, alkoxyl group, hydroxyl, sulfonic group, arylsulfonyl, carboxyl, nitro, imido grpup, carbonyl, ester group, carbalkoxy, itrile group, fluorine, chlorine, bromine, iodine; R
2For hydrogen atom, alkyl, aryl, heteroaryl, alkoxyl group, hydroxyl, arylsulfonyl, nitro, imido grpup, carbonyl, carbalkoxy, itrile group; Metal catalyst is that the various salt compounds of palladium, copper are as cuprous iodide, cuprous bromide, cuprous chloride, neutralized verdigris, copper trifluoromethanesulfcomposite, cupric fluoride, Palladous chloride, palladium, palladium trifluoroacetate; Part is 2,2-dipyridyl, 1,10-phenanthroline, 4,7-phenylbenzene-1,10-phenanthroline, pyridine, triphenylphosphine, two (diphenylphosphine) ethane of 1,2-.
R is hydrogen atom, alkyl, aryl, heteroaryl, alkoxyl group, hydroxyl, sulfonic group, arylsulfonyl, carboxyl, nitro, imido grpup, carbonyl, ester group, carbalkoxy, itrile group, fluorine, chlorine, bromine, iodine; Metal catalyst is that the various salt compounds of palladium, copper are as cuprous iodide, cuprous bromide, cuprous chloride, neutralized verdigris, copper trifluoromethanesulfcomposite, cupric fluoride, Palladous chloride, palladium, palladium trifluoroacetate; Part is 2,2-dipyridyl, 1,10-phenanthroline, 4,7-phenylbenzene-1,10-phenanthroline, pyridine, triphenylphosphine, two (diphenylphosphine) ethane of 1,2-.
Technical scheme of the present invention is as follows:
The method that catalyzes and synthesizes benzyl amine derivative comprises following experiment condition and step:
Take various toluene derivatives as raw material; In reaction, used catalyst is: cuprous iodide, cuprous bromide, cuprous chloride, neutralized verdigris, copper trifluoromethanesulfcomposite, cupric fluoride, Palladous chloride, palladium, palladium trifluoroacetate; Part used is: 2,2-dipyridyl, 1,10-phenanthroline, 4,7-phenylbenzene-1,10-phenanthroline, pyridine, triphenylphosphine, two (diphenylphosphine) ethane of 1,2-.Add above-mentioned benzyl methyl or the benzylidenei compound (1.0 mmole) and NFSI (1.1 mmole) of containing in organic solvent acetonitrile (4.0-8.0 milliliter), add the above-mentioned a certain class catalyzer (0.1 mmole) of mentioning, part (0.1 mmole), (above quantity can be amplified in proportion).Finish, 100 ℃～130 ℃ of oil baths are stirred between 1 hour～24 hours, through aftertreatment, separate and obtain benzyl amine derivative, and productive rate is looked differential responses between 40-91%, sees the embodiment in embodiment for details.
Description of drawings
Fig. 1 is N-benzyl-N-(benzenesulfonyl) benzsulfamide
1The H-NMR nuclear magnetic resonance spectrum;
Fig. 2 is N-(4-methyl-benzyl)-N-(benzenesulfonyl) benzsulfamide
1The H-NMR nuclear magnetic resonance spectrum;
Fig. 3 is N-(3,5-dimethyl benzyl)-N-(benzenesulfonyl) benzsulfamide
1The H-NMR nuclear magnetic resonance spectrum;
Fig. 4 is N-(2,3,4,5,6-pentamethyl-benzyl)-N-(benzenesulfonyl) benzsulfamide
1The H-NMR nuclear magnetic resonance spectrum;
Fig. 5 is 4-((N-(benzenesulfonyl) benzene sulfonamido) methyl) phenyl pivalate
1The H-NMR nuclear magnetic resonance spectrum;
Fig. 6 is N, N '-(Isosorbide-5-Nitrae-two (methylene radical) phenyl) two (N-(benzenesulfonyl) benzsulfamide)
1The H-NMR nuclear magnetic resonance spectrum.
Embodiment
Embodiment 1:
In 25 milliliters of round-bottomed flasks, add 0.092 gram (1.0 mmole) toluene, 0.346 gram (1.1 mmole) NFSI, 0.014 gram (0.1 mmole) cuprous bromide, 0.016 gram 2,2-dipyridyl (0.1 mmole), heat 110 ℃, refluxes 1.5 hours to toluene react completely (thin-layer chromatography TLC monitoring).In reaction mixture impouring 20 ml waters, with saturated sodium bicarbonate, be neutralized to neutrality.With dichloromethane extraction (10 milliliters * 3).Merge organic phase, with anhydrous magnesium sulfate drying.After steaming desolventized, (elutriant: petrol ether/ethyl acetate=9/1) obtain white solid was N-benzyl-N-(benzenesulfonyl) benzsulfamide 0.290 gram to residuum, productive rate 75% through the silica gel column chromatography separation.Following formula is seen in reaction:
The spectrum elucidation data
1H?NMR(500MHz；CDCl
3)：δ＝4.94(s，2H)，7.24(t，J＝7.5Hz，3H)，7.36(d，J＝7.0Hz，2H)，7.41(t，J＝8.0Hz，4H)，7.54(t，J＝7.0Hz，2H)，7.78(d，J＝8.0Hz，4H).
Embodiment 2:
In 25 milliliters of round-bottomed flasks, add 0.106 gram (1.0 mmole) p-Xylol, 0.346 gram (1.1 mmole) NFSI, 0.010 gram (0.1 mmole) cupric fluoride, 0.020 gram (0.1 mmole) 1, the 10-phenanthroline, heat 100 ℃, refluxes 1.5 hours to p-Xylol react completely (thin-layer chromatography TLC monitoring).In reaction mixture impouring 20 ml waters, with saturated sodium bicarbonate, be neutralized to neutrality.With dichloromethane extraction (10 milliliters * 3).Merge organic phase, with anhydrous magnesium sulfate drying.After steaming desolventized, (elutriant: petrol ether/ethyl acetate=10/1) obtain white solid was N-(4-methyl-benzyl)-N-(benzenesulfonyl) benzsulfamide 0.341 gram to residuum, productive rate 85% through the silica gel column chromatography separation.Following formula is seen in reaction:
The spectrum elucidation data
1H?NMR(500MHz；CDCl
3)：δ＝2.33(s，3H)，4.89(s，2H)，7.03(d，J＝8.0Hz，2H)，7.25(d，J＝8.0Hz，2H)，7.42(t，J＝7.5Hz，4H)，7.56(t，J＝7.5Hz，2H)，7.77(t，J＝7.5Hz，4H).
Embodiment 3:
In 25 milliliters of round-bottomed flasks, add 0.120 gram (1.0 mmole) sym-trimethylbenzene, 0.346 gram (1.1 mmole) NFSI, 0.019 gram (0.1 mmole) cuprous iodide, 0.008 gram (0.1 mmole) pyridine, heat 130 ℃, reflux 1.5 hours to sym-trimethylbenzene react completely (thin-layer chromatography TLC monitoring).In reaction mixture impouring 20 ml waters, with saturated sodium bicarbonate, be neutralized to neutrality.With dichloromethane extraction (10 milliliters * 3).Merge organic phase, with anhydrous magnesium sulfate drying.After steaming desolventized, (elutriant: petrol ether/ethyl acetate=9/1) obtain white solid was N-(3,5-dimethyl benzyl)-N-(benzenesulfonyl) benzsulfamide 0.352 gram to residuum, productive rate 85% through the silica gel column chromatography separation.Following formula is seen in reaction:
The spectrum elucidation data
1H?NMR(500MHz；CDCl
3)：δ＝2.17(s，6H)，4.88(s，2H)，6.86(s，1H)，6.88(s，2H)，7.42(t，J＝7.5Hz，4H)，7.54-7.57(m，2H)，7.80(d，J＝7.5Hz，4H).
Embodiment 4:
In 25 milliliters of round-bottomed flasks, add 0.162 gram (1.0 mmole) hexamethyl-benzene, 0.346 gram (1.1 mmole) NFSI, 0.014 gram (0.1 mmole) cuprous bromide, 0.020 gram (0.1 mmole) 1, the 10-phenanthroline, heat 120 ℃, refluxes 1.5 hours to hexamethyl-benzene react completely (thin-layer chromatography TLC monitoring).In reaction mixture impouring 20 ml waters, with saturated sodium bicarbonate, be neutralized to neutrality.With dichloromethane extraction (10 milliliters * 3).Merge organic phase, with anhydrous magnesium sulfate drying.After steaming desolventized, (elutriant: petrol ether/ethyl acetate=10/1) obtain white solid was N-(2,3,4,5,6-pentamethyl-benzyl)-N-(benzenesulfonyl) benzsulfamide 0.411 gram to residuum, productive rate 90% through the silica gel column chromatography separation.Following formula is seen in reaction:
The spectrum elucidation data
1H?NMR(500MHz；CDCl
3)：δ＝2.01(s，6H)，2.15(s，6H)，2.18(s，3H)，5.31(s，2H)，7.34-7.37(m，4H)，7.51-7.55(m，2H)，7.64-7.66(m，4H).
Embodiment 5:
In 25 milliliters of round-bottomed flasks, add 0.192 gram (1.0 mmole) p-methylphenyl pivalate, 0.346 gram (1.1 mmole) NFSI, 0.014 gram (0.1 mmole) cuprous bromide, 0.016 gram 2,2-dipyridyl (0.1 mmole), heat 110 ℃, refluxes 3 hours to p-methylphenyl pivalate react completely (thin-layer chromatography TLC monitoring).In reaction mixture impouring 20 ml waters, with saturated sodium bicarbonate, be neutralized to neutrality.With dichloromethane extraction (10 milliliters * 3).Merge organic phase, with anhydrous magnesium sulfate drying.After steaming desolventized, (elutriant: petrol ether/ethyl acetate=10/1) obtain white solid was 4-((N-(benzenesulfonyl) benzene sulfonamido) methyl) phenyl pivalate 0.443 gram to residuum, productive rate 91% through the silica gel column chromatography separation.Following formula is seen in reaction:
The spectrum elucidation data
1H?NMR(500MHz；CDCl
3)：δ＝1.38(s，9H)，4.91(s，2H)，6.92(d，J＝8.5Hz，2H)，7.40(d，J＝8.5Hz，2H)，7.46(t，J＝7.5Hz，4H)，7.58(t，J＝7.5Hz，2H)，7.76(d，J＝7.0Hz，4H).
Embodiment 6:
In 25 milliliters of round-bottomed flasks, add 0.106 gram (1.0 mmole) p-Xylol, 1.575 gram (5.0 mmole) NFSI, 0.01 gram (0.1 mmole) cupric fluoride, 0.020 gram (0.1 mmole) 1, the 10-phenanthroline, heat 120 ℃, refluxes 20 hours to p-Xylol react completely (thin-layer chromatography TLC monitoring).In reaction mixture impouring 20 ml waters, with saturated sodium bicarbonate, be neutralized to neutrality.With dichloromethane extraction (10 milliliters * 3).Merge organic phase, with anhydrous magnesium sulfate drying.After steaming desolventizes; (elutriant: petrol ether/ethyl acetate=10/1) obtain white solid is N to residuum through the silica gel column chromatography separation; N '-(Isosorbide-5-Nitrae-two (methylene radical) phenyl) two (N-(benzenesulfonyl) benzsulfamide) 0.431 gram, productive rate 62%.Following formula is seen in reaction:
The spectrum elucidation data
1H?NMR(500MHz；CDCl
3)：δ＝4.91(s，4H)，7.26(s，4H)，7.45(t，J＝7.5Hz，8H)，7.59(t，J＝7.5Hz，4H)，7.82(d，J＝8.0Hz，8H).
Claims (5)
1. the hydrocarbon direct aminatin method of the benzyl of a toluene derivative is characterized in that comprising following condition and step:
Take toluene, p-Xylol, sym-trimethylbenzene, hexamethyl-benzene and tolyl pivalate as raw material; In reaction, used catalyst is: cuprous iodide, cuprous bromide, cuprous chloride, neutralized verdigris, copper trifluoromethanesulfcomposite, cupric fluoride, Palladous chloride, palladium, palladium trifluoroacetate; Part used is: 2, the 2-dipyridyl, 1, the 10-phenanthroline, 4,7-phenylbenzene-1, the 10-phenanthroline, pyridine, triphenylphosphine, 1, the two diphenyl phosphine oxides of 2-, add above-mentioned benzyl methyl or benzylidenei compound and 1.1 mmole NFSI, a certain class catalyzer that adds above-mentioned 0.1 mmole to mention, the 0.1 mmole part of containing of 1.0 mmoles in 4.0-8.0 milliliter organic solvent acetonitrile, finish, 100 ℃-130 ℃ stirring 1-24 hour of oil bath, separate and obtain benzyl amine derivative through aftertreatment, and productive rate is looked differential responses between 40-91%.
2. the amount ratio that in accordance with the method for claim 1, it is characterized in that catalyzer and toluene derivative is 0.02-0.1: 1.
3. the amount ratio that in accordance with the method for claim 1, it is characterized in that part and toluene derivative is 0.05～0.1: 1.
4. in accordance with the method for claim 1, it is characterized in that temperature is controlled at 100 ℃-110 ℃, solvent is acetonitrile, between reaction times 12-18 hour.
5. the amount ratio that in accordance with the method for claim 1, it is characterized in that NFSI and p-Xylol is 4～6: 1.
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| CN103524397B (en) * | 2013-10-17 | 2016-02-10 | 湘潭大学 | A kind of 3-sulfimide base Benzazole compounds and preparation method thereof |
| CN107253925A (en) * | 2017-08-01 | 2017-10-17 | 盐城师范学院 | N alkyl/alkenyl sulfimide derivative, its preparation method and application |
| CN107266414A (en) * | 2017-08-18 | 2017-10-20 | 宁夏大学 | A kind of synthetic method of aminomethyl thiophenes |
| CA3083593A1 (en) | 2017-12-01 | 2019-06-06 | The Scripps Research Institute | Direct oxidative amination of hydrocarbons |
| CN110003061B (en) * | 2019-05-06 | 2021-04-02 | 河南农业大学 | Method for direct amination of methyl aromatic compound benzyl hydrocarbon under catalysis of iron |
| CN112047925B (en) * | 2020-09-16 | 2021-06-25 | 中国科学院兰州化学物理研究所 | Preparation method of N- (aryl/heteroaryl) alkyl-diamide |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| US3900459A (en) * | 1972-11-16 | 1975-08-19 | Dainichiseika Color Chem | Process for preparing high molecular weight azo pigment |
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| US3900459A (en) * | 1972-11-16 | 1975-08-19 | Dainichiseika Color Chem | Process for preparing high molecular weight azo pigment |
Non-Patent Citations (4)
| Title |
|---|
| Kai Sun, et al.Palladium-Catalyzed C-H Aminations of Anilides with N-Fluorobenzenesulfonimide.《Journal of the american chemical society》.2011,第133卷第1694-1697页. |
| Palladium-Catalyzed C-H Aminations of Anilides with N-Fluorobenzenesulfonimide;Kai Sun, et al;《Journal of the american chemical society》;20110220;第133卷;第1694-1697页 * |
| Remote amide-directed palladium-catalyzed benzylic C-H amination with N-fluorobenzenesulfonimide;Tao Xiong,et al;《chem.commun》;20100726;第46卷(第36期);第6831-6833页 * |
| Tao Xiong,et al.Remote amide-directed palladium-catalyzed benzylic C-H amination with N-fluorobenzenesulfonimide.《chem.commun》.2010,第46卷(第36期),第6831-6833页. |
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