CN111848412B - Method for efficiently realizing N-alkylation reaction by using cycloiridium catalyst - Google Patents
Method for efficiently realizing N-alkylation reaction by using cycloiridium catalyst Download PDFInfo
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Abstract
The invention discloses a method for efficiently realizing N-alkylation reaction by using a cycloiridium catalyst, belonging to the technical field of pharmaceutical chemical synthesis. The invention takes amine and alcohol compounds as raw materials, takes a cycloiridium complex as a catalyst, takes water or an organic solvent as a reaction medium, and is heated and stirred for reaction for 12-24 hours under the protection of inert gas, after the reaction is finished, the reaction is cooled to room temperature, reduced pressure distillation and concentration are carried out to obtain a crude product, and then a series of amine compounds are obtained through column chromatography purification. The synthesis method of the amine compound has the advantages of simple operation, easily available raw materials, low price, high reaction efficiency, N-alkylation selectivity, good adaptability to various functional groups, wide universality to substrates, environmental friendliness, gram-level performance, wide application prospect in the fields of medicine, organic synthesis and the like, and shows the potential of industrially synthesizing the N-alkylamine compound.
Description
Technical Field
The invention belongs to the technical field of pharmaceutical chemical synthesis, and particularly relates to a method for efficiently realizing N-alkylation reaction by using a cycloiridium catalyst.
Background
Amines and their derivatives are widely found in various natural products and are the basic building blocks of many natural products, bioactive molecules and drug molecules. In the field of pharmaceutical chemistry, it has a wide range of uses, such as Rivastigmine (Rivastigmine) as a drug for treating senile dementia, cinacalcet (Cinacalcet) as a drug for treating severe renal failure and primary hyperparathyroidism, levocetirizine (Levocetirizine) as a drug for treating allergic diseases at the respiratory system, skin and eyes, etc., and Ezetimibe (Ezetimibe) as a drug for reducing coronary heart disease for selectively inhibiting the absorption of cholesterol in the intestines, resulting in a significant reduction of cholesterol levels, in patients with hypercholesterolemia (Afanasyev, o.i.; kuchuk, e., usanov, d.l., chunov, d.chem.rev.2019, 119, 11857, barnio-Xicota, m., leiva, r., escolo, c., V, zquez, s.synthesis 2016,48,783, kong, d., li, m., zi, g., hou, g., he, y.j., org., chem.2016,81,6640, busscher, g.f., lefort, l., cremers, j.g., o., mottinelli, m., wiert, r.w., de Lange, b., okamura, y, yusa, y, matsura, k, k., shimmy, h., vrher, etc., vrher, etc.
Because of the potential medicinal value of the compounds, the compounds attract great interest of the world chemists to study the compounds. In recent years, chemists have developed methods for synthesizing such compounds, specifically the following: (1) Using enamine or imine as a substrate, and carrying out asymmetric hydrogenation under the action of metal and chiral ligand. The catalyst for the reaction is mainly a transition metal (Chen, j.; zhang, z.; li, B; the present invention relates to a process for the preparation of a catalyst for asymmetric hydrogenation of a metal, comprising the steps of (i) Li, f, wang, y, zhao, m, gridnev, i.d., imamoto, t., zhang, w.nature command, 2018,9:5000, pan, h, -j, zhang, y, shan, c, yu, z, lan, y, zhao, Y.Angew.Chem.Int.Ed.2016,55,9615;Chen,Y, he, y, -m, zhang, s, miao, t., fanq, q, h.angelw.e.2019, 58,3809, whereas the onset of the study of the inexpensive metal for asymmetric hydrogenation is later (Li, b, chen, j, zhang, z, gridnev, i.d., zhang, W.Angew.Chem.Int.Ed.2019,58,15767;Hu,Y, zha, z, y, zhao, t., temperature, fang, y, and h.angelw.e.2019, 58,3809, and the like, the study of the asymmetric hydrogenation of the metal is further developed on the substrate, i.e.m., 62, m., m, g., m, g., m, g, m, g., g, m, g, m, g). (2) The chiral amine compound can be directly obtained by taking the carbonyl compound as a substrate and performing reductive amination with the amine compound, so that the chiral amine compound has certain advantages (Lou, Y.; hu, Y.; lu, J.; guan, F.; gong, G.; yin, Q.; zhang, X.Angew.Chem.Int.Ed.2018,57,14193;Hu,L.; zhang, Y.; zhang, Q.; yin, Q.; zhang, X.Angew.chem.int. Ed.2020,59,5321.). There are still some challenges, such as: carbonyl groups themselves can also be reduced and the condensation to form imines is reversible in one step, leading to problems of chemoselectivity; the amine source used in the reaction or the product obtained by reductive amination can have poisoning effect on the metal catalyst, so that the reaction efficiency is lower; the addition of organic electron-rich or organometallic reagents to imines is also an important method for the synthesis of amine compounds (Jang, h.; romiti, f.; torker, s.; hoveyda, a.h. nature chem.2017,9,1269; zhu, j.; huang, l.; dong, w.; li, n.; yu, x.; deng, w.+ -. P.; tang, W.Angew.Chem.Int.Ed.2019,58,16119;Wang,Y.; ian, j.+ -. S.; tan, p.+ -. W.; cao, q.; zhang, x.; cao, z.+ -. Y.; zhou, f.; wang, x.angel.chem.int.ed.2020, 59,1634). Compared with the two methods, the strategy can synthesize chiral amine compounds containing quaternary carbon chiral centers. Although the addition of imines using organometallic reagents is an effective method for obtaining amines, conventional organometallic reagents suffer from some inherent disadvantages or drawbacks such as being expensive, relatively toxic, sensitive to water and air, even requiring on-site preparation, adverse handling, etc. In recent years, organoboron reagents have been increasingly favored for use in organic synthesis because of their low toxicity, stability, direct market availability, etc. (Yeung, K.; ruscoe, R.E.; rae, J.; pulis, A.P.; procter, D.J.Angew.Chem.Int.Ed.2016,55,11912;Chen,D.; xu, M.; H.Chin.J.Org.Chem.2017,37,1589;Jiang,T.; chen, W.; xu, M.; H.Org.Lett.2017,19,2138;He,Q.; wu, L.; kou, X.; butt, N.; yang, G.; zhang, W.org. Lett.2016,18,288.). The organoboron reagent is metallated by transfer to form the corresponding organometallic active species which participate in the reaction under catalysis of a suitable transition metal such as rhodium, palladium or the like.
Nevertheless, the existing methods for synthesizing amine compounds still have some problems and challenges. Such as: some amination reactions have poor catalytic efficiency; the transition metal is used as a catalyst, and is expensive, not friendly to the environment, and a new metal catalytic system needs to be constructed; the ligand has complex structure and complex synthesis. Therefore, the design and synthesis of simple, easy-to-synthesize and efficient novel ligands and the application thereof in the catalytic synthesis of amine compounds are still important points of research in the future.
Disclosure of Invention
The invention aims to solve the defects of the prior art and provide a method for efficiently realizing N-alkylation reaction by using a cycloiridium catalyst, which has the advantages of simple operation, available raw materials, low price, high reaction efficiency (S/C is up to 10000, yield is up to 96%) and N-alkylation selectivity (up to > 99:1), good adaptability to various functional groups, wide substrate universality, environmental friendliness and capability of industrially synthesizing N-alkylamine compounds.
The invention adopts the following technical scheme:
the method for efficiently realizing the N-alkylation reaction by using the cycloiridium catalyst comprises the following steps: taking amine compounds and alcohol compounds as raw materials, taking a cycloiridium complex as a catalyst, taking water or an organic solvent as a reaction medium, heating and stirring for reaction for 12-24 hours under the protection of inert gas, and after the reaction is finished, obtaining a series of amine compounds through post-treatment; the N-alkylation reaction is represented by the following formula:
wherein R is 1 Is one of phenyl, 3-chlorophenyl, 4-chlorophenyl, 2-methoxyphenyl, 3-methoxyphenyl, 4-fluorophenyl, 3, 4-dichlorophenyl, 4-methylphenyl, 1-naphthyl, 2-naphthyl, thienyl, furyl, n-butyl or cyclohexyl;
R 2 is one of hydrogen or methyl;
R 3 is one of ethyl, phenyl, 2-methylphenyl, 3-methylphenyl, 4-methoxyphenyl, 4-chlorophenyl, 4-fluorophenyl, 4-methyl-3-bromophenyl or N- (4-methoxyphenyl) piperazinyl.
Further, the inert gas is one of nitrogen, argon or helium
Further, the molar ratio of the addition amount of the alcohol compound to the amine compound is 1-1.2: 1.
still further, the cycloiridium complex is one of [2- (4, 5-dihydro-1H-imidazol-2-yl) pyridine ] (pentamethylcyclopentadienyl) iridium (III) chloride, [2- (4, 5-dihydro-1H-imidazol-2-yl) -4-chloropyridine ] (pentamethylcyclopentadienyl) iridium (III) chloride, mono [2- (4, 5-dihydro-1H-imidazol-2-yl) -4-methylpyridinyl ] (pentamethylcyclopentadienyl) iridium (III) chloride, mono [2- (4, 5-dihydro-1H-imidazol-2-yl) -4-methoxypyridine ] (pentamethylcyclopentadienyl) iridium (III) chloride, mono [2- (4, 5-dihydro-1H-imidazol-2-yl) -6-fluoropyridine ] (pentamethylcyclopentadienyl) iridium (III) chloride, or mono [2- (4, 5-dihydro-1H-imidazol-2-yl) -6-methoxypyridine ] (pentamethylcyclopentadienyl) chloride.
Further, the molar ratio of the addition of the cycloiridium complex to the amine compound is 0.01-0.1: 1.
further, the organic solvent is one of toluene, xylene, 1, 2-dimethylglycol, tetrahydrofuran or N, N-dimethylformamide.
Still further, the N-alkylation reaction is performed under alkaline conditions, and the base is one of potassium tert-butoxide, sodium acetate, potassium acetate, sodium formate, potassium carbonate, sodium carbonate, potassium hydroxide or sodium hydroxide.
Further, the molar ratio of the alkali to the alcohol compound is 1-1.5: 1.
further, the temperature of the heating and stirring reaction is 60-110 ℃.
Further, after the reaction is finished, cooling to room temperature, performing reduced pressure distillation and concentration to obtain a crude product, and purifying by column chromatography to obtain a series of amine compounds, wherein the column chromatography eluent is pure petroleum ether or mixed solvent; the mixed solvent is a mixed solvent of petroleum ether and ethyl acetate, wherein the volume ratio of petroleum ether to ethyl acetate is 10-50:1.
The principle of the invention is that the amine compound and the alcohol compound are used as raw materials, and the N-alkylation reaction is carried out by taking water as a reaction medium under the catalysis of the cycloiridium complex to produce the amine compound. The method has the advantages of simple operation, easily available raw materials, low price, high reaction efficiency, N-alkylation selectivity, wide universality on substrates, environmental friendliness and the like, and thus has potential practical value.
Compared with the prior art, the invention has the beneficial effects that:
the synthesis method of the amine compound has the advantages of simple operation, easily available raw materials, low cost, high reaction efficiency, N-alkylation selectivity, wide universality on substrates, environmental friendliness and the like, and thus has potential practical value.
Drawings
FIG. 1 is a hydrogen spectrum of the product obtained in example 1;
FIG. 2 is a carbon spectrum of the product obtained in example 1;
FIG. 3 is a hydrogen spectrum of the product obtained in example 2;
FIG. 4 is a carbon spectrum of the product obtained in example 2;
FIG. 5 is a hydrogen spectrum of the product obtained in example 3;
FIG. 6 is a carbon spectrum of the product obtained in example 3;
FIG. 7 is a hydrogen spectrum of the product obtained in example 4;
FIG. 8 is a carbon spectrum of the product obtained in example 4;
FIG. 9 is a hydrogen spectrum of the product obtained in example 5;
FIG. 10 is a carbon spectrum of the product obtained in example 5;
FIG. 11 is a hydrogen spectrum of the product obtained in example 6;
FIG. 12 is a carbon spectrum of the product obtained in example 6;
FIG. 13 is a hydrogen spectrum of the product obtained in example 7;
FIG. 14 is a carbon spectrum of the product obtained in example 7;
FIG. 15 is a hydrogen spectrum of the product obtained in example 8;
FIG. 16 is a carbon spectrum of the product obtained in example 8;
FIG. 17 is a hydrogen spectrum of the product obtained in example 9;
FIG. 18 is a carbon spectrum of the product obtained in example 9;
FIG. 19 is a hydrogen spectrum of the product obtained in example 10;
FIG. 20 is a carbon spectrum of the product obtained in example 10;
FIG. 21 is a hydrogen spectrum of the product obtained in example 11;
FIG. 22 is a carbon spectrum of the product obtained in example 11;
FIG. 23 is a hydrogen spectrum of the product obtained in example 12;
FIG. 24 is a carbon spectrum of the product obtained in example 12;
FIG. 25 is a hydrogen spectrum of the product obtained in example 13;
FIG. 26 is a carbon spectrum of the product obtained in example 13;
FIG. 27 is a hydrogen spectrum of the product obtained in example 14;
FIG. 28 is a carbon spectrum of the product obtained in example 14;
FIG. 29 is a hydrogen spectrum of the product obtained in example 15;
FIG. 30 is a carbon spectrum of the product obtained in example 15;
FIG. 31 is a hydrogen spectrum of the product obtained in example 16;
FIG. 32 is a carbon spectrum of the product obtained in example 16;
FIG. 33 is a hydrogen spectrum of the product obtained in example 17;
FIG. 34 is a carbon spectrum of the product obtained in example 17;
FIG. 35 is a hydrogen spectrum of the product obtained in example 18;
FIG. 36 is a carbon spectrum of the product obtained in example 18;
FIG. 37 is a hydrogen spectrum of the product obtained in example 19;
FIG. 38 is a carbon spectrum of the product obtained in example 19;
FIG. 39 is a hydrogen spectrum of the product obtained in example 20;
FIG. 40 is a carbon spectrum of the product obtained in example 20;
FIG. 41 is a hydrogen spectrum of the product obtained in example 21;
FIG. 42 is a carbon spectrum of the product obtained in example 21;
FIG. 43 is a hydrogen spectrum of the product obtained in example 22;
FIG. 44 is a carbon spectrum of the product obtained in example 22;
FIG. 45 is a hydrogen spectrum of the product obtained in example 23;
FIG. 46 is a carbon spectrum of the product obtained in example 23;
FIG. 47 is a hydrogen spectrum of the product obtained in example 24;
FIG. 48 is a carbon spectrum of the product obtained in example 24;
Detailed Description
The present invention is further illustrated below with reference to specific embodiments and the accompanying drawings, it being understood that these embodiments are only for the purpose of illustrating the invention and not for the purpose of limiting the same, and that various modifications of the invention in its equivalent form will fall within the scope of the appended claims after reading the present invention.
EXAMPLE 1 preparation of N-benzylaniline from benzyl alcohol and aniline
Into a 10mL Schlenk tube, benzyl alcohol (1.1 mmol), aniline (1.0 mmol), KOH (1.1 mmol), H were added 2 O (2.0 mL) and chloromono- (2- (4, 5-dihydro-1H-imidazol-2-yl) -6-methyl)Oxopyridines](pentamethylcyclopentadienyl) iridium (III) (0.1 mol%). Under the protection of nitrogen, heating to 80 ℃ for reaction. After completion of the extraction with ethyl acetate (3×5.0 mL), the organic layers were combined, dried over anhydrous magnesium sulfate, and the solvent was concentrated under reduced pressure to give a crude product. The crude product was purified by silica gel chromatography using a mixture of ethyl acetate/petroleum ether (1/20) as eluent to give the pure product in 95% yield.
The structural characterization data of the product obtained in example 1 are shown below:
colorless oil, 1 H NMR(400MHz,CDCl 3 )δ7.60-7.51(m,4H),7.51-7.45(m,1H),7.39(dd,J＝8.5,7.4Hz,2H),6.95(t,J＝7.3Hz,1H),6.82(dd,J＝8.5,0.8Hz,2H),4.49(s,2H),4.16(s,1H)；
13 C NMR(101MHz,CDCl 3 )δ148.4,139.7,129.5,128.9,127.7,127.4,117.8,113.1,48.5.
the structure of the resulting product is deduced from the above data as follows:
EXAMPLE 2 preparation of N- (3-chlorobenzyl) aniline from 3-chlorobenzyl alcohol and aniline
In a 10mL Schlenk tube, 3-chlorobenzyl alcohol (1.1 mmol), aniline (1.0 mmol), KOH (1.1 mmol), H were added 2 O (2.0 mL) and chloromono [2- (4, 5-dihydro-1H-imidazol-2-yl) -6-methoxypyridine](pentamethylcyclopentadienyl) iridium (III) (0.1 mol%). Under the protection of nitrogen, heating to 80 ℃ for reaction. After completion of the extraction with ethyl acetate (3×5.0 mL), the organic layers were combined, dried over anhydrous magnesium sulfate, and the solvent was concentrated under reduced pressure to give a crude product. The crude product was purified by silica gel chromatography using a mixture of ethyl acetate/petroleum ether (1/20) as eluent to give the pure product in 93% yield.
The structural characterization data of the product obtained in example 2 are shown below:
colorless oil, 1 H NMR(400MHz,CDCl 3 )δ7.47(br,1H),7.36–7.28(m,5H),6.86(t,J＝7.3Hz,1H),6.71(d,J＝8.1Hz,2H),4.38(s,2H),4.14(s,1H)；
13 C NMR(101MHz,CDCl 3 )δ147.9，141.9，134.6,130.0,129.5,127.5,127.5,,125.5,117.9,113.0,47.8.
the structure of the resulting product is deduced from the above data as follows:
EXAMPLE 3 preparation of N- (4-chlorobenzyl) aniline from 4-chlorobenzyl alcohol and aniline
In a 10mL Schlenk tube, 4-chlorobenzyl alcohol (1.1 mmol), aniline (1.0 mmol), KOH (1.1 mmol), H were added 2 O (2.0 mL) and chloromono [2- (4, 5-dihydro-1H-imidazol-2-yl) -6-methoxypyridine](pentamethylcyclopentadienyl) iridium (III) (0.1 mol%). Under the protection of nitrogen, heating to 80 ℃ for reaction. After completion of the extraction with ethyl acetate (3×5.0 mL), the organic layers were combined, dried over anhydrous magnesium sulfate, and the solvent was concentrated under reduced pressure to give a crude product. The crude product was purified by silica gel chromatography using a mixture of ethyl acetate/petroleum ether (1/20) as eluent to give the pure product in 96% yield.
The structural characterization data of the product obtained in example 3 are shown below:
colorless oil, 1 H NMR(400MHz,CDCl 3 )δ7.42–7.37(m,4H),7.31–7.27(m,2H),6.85(t,J＝7.3Hz,1H),6.71(d,J＝8.0Hz,2H),4.38(s,2H),4.12(s,1H)；
13 C NMR(101MHz,CDCl 3 )δl48.0,138.2,132.9,129.4,128.9,128.8,117.9,113.0,47.7.
the structure of the resulting product is deduced from the above data as follows:
EXAMPLE 4 preparation of N- (2-methoxybenzyl) aniline from 2-methoxybenzyl alcohol and aniline
In a 10mL Schlenk tube, 2-methoxybenzyl alcohol (1.1 mmol), aniline (1.0 mmol), KOH (1.1 mmol), H were added 2 O (2.0 mL) and chloromono [2- (4, 5-dihydro-1H-imidazol-2-yl) -6-methoxypyridine](pentamethylcyclopentadienyl) iridium (III) (0.1 mol%). Under the protection of nitrogen, heating to 80 ℃ for reaction. After completion of the extraction with ethyl acetate (3×5.0 mL), the organic layers were combined, dried over anhydrous magnesium sulfate, and the solvent was concentrated under reduced pressure to give a crude product. The crude product was purified by silica gel chromatography using a mixture of ethyl acetate/petroleum ether (1/20) as eluent to give the pure product in 90% yield.
The structural characterization data of the product obtained in example 4 are shown below:
yellow solid,mp 91-92℃, 1 H NMR(400MHz,CDCl 3 )δ7.42(d，J＝7.4Hz,1H),7.36(td,J＝8.0,1.5Hz,1H),7.30–7.26(m,2H),7.01(dd,J＝17.2,7.9Hz,2H),6.81(t,J＝7.3Hz,1H),6.76(d,J＝7.8Hz,2H),4.44(s,2H),4.22(s,1H),3.95(s,3H)；
13 C NMR(101MHz,CDCl 3 )δ157.5,148.5,129.3,129.0,128.4,127.4,120.6,117.4,113.2,110.3,55.4,43.5.
the structure of the resulting product is deduced from the above data as follows:
EXAMPLE 5 preparation of N- (3-methoxybenzyl) aniline from 3-methoxybenzyl alcohol and aniline
In a 10mL Schlenk tube, 2-methoxybenzyl alcohol (1.1 mmol), aniline (1.0 mmol), KOH (1.1 mmol), H were added 2 O (2.0 mL) and chloromono [2- (4, 5-dihydro-1H-imidazol-2-yl) -6-methoxypyridine](pentamethylcyclopentadienyl) iridium (III) (0.1 mol%). Under the protection of nitrogen, heating to 80 ℃ for reaction. After completion of the extraction with ethyl acetate (3×5.0 mL), the organic layers were combined, dried over anhydrous magnesium sulfate, and the solvent was concentrated under reduced pressure to give a crude product. The crude product was eluted with a mixture of ethyl acetate/petroleum ether (1/20) by chromatography on silica gelThe crude product obtained was purified to give the pure product in 91% yield.
The structural characterization data of the product obtained in example 5 are shown below:
colorless oil, 1 H NMR(400MHz,CDCl 3 )δ7.39(t,J＝7.8Hz,1H),7.31(t,J＝7.8Hz,2H),7.10–7.07(m,2H),6.95(dd,J＝8.2,2.4Hz,1H),6.86(t,J＝7.3Hz,1H),6.75(d,J＝8.2Hz,2H),4.40(s,2H),4.15(s,1H),3.90(s,3H)；
13 C NMR(101MHz,CDCl 3 )δ160.0,148.3,141.4,129.8,129.4,119.9,117.7,113.2,113.0,112.7,55.3,48.4.
the structure of the resulting product is deduced from the above data as follows:
EXAMPLE 6 preparation of N- (4-methoxybenzyl) aniline from 4-methoxybenzyl alcohol and aniline
In a 10mL Schlenk tube, 4-methoxybenzyl alcohol (1.1 mmol), aniline (1.0 mmol), KOH (1.1 mmol), H were added 2 O (2.0 mL) and chloromono [2- (4, 5-dihydro-1H-imidazol-2-yl) -6-methoxypyridine](pentamethylcyclopentadienyl) iridium (III) (0.1 mol%). Under the protection of nitrogen, heating to 80 ℃ for reaction. After completion of the extraction with ethyl acetate (3×5.0 mL), the organic layers were combined, dried over anhydrous magnesium sulfate, and the solvent was concentrated under reduced pressure to give a crude product. The crude product was purified by silica gel chromatography using a mixture of ethyl acetate/petroleum ether (1/20) as eluent to give the pure product in 93% yield.
The structural characterization data of the product obtained in example 6 are shown below:
colorless oil, 1 H NMR(400MHz,CDCl 3 )δ7.41(d,J＝8.6Hz,2H),7.34-7.30(m,2H),7.03-7.01(m,2H),6.86(t,J＝7.3Hz,1H),6.76(d,J＝7.7Hz,2H),4.36(s,2H),4.07(s,1H),3.91(s,3H)；
13 C NMR(101MHz,CDCl 3 )δ159.0,148.4,131.6,129.4,128.9,117.6,114.2,113.0,55.4,47.9.
the structure of the resulting product is deduced from the above data as follows:
EXAMPLE 7 preparation of N- (4-methylbenzyl) aniline from 4-methylbenzyl alcohol and aniline
In a 10mL Schlenk tube, 4-methylbenzyl alcohol (1.1 mmol), aniline (1.0 mmol), KOH (1.1 mmol), H were added 2 O (2.0 mL) and chloromono [2- (4, 5-dihydro-1H-imidazol-2-yl) -6-methoxypyridine](pentamethylcyclopentadienyl) iridium (III) (0.1 mol%). Under the protection of nitrogen, heating to 80 ℃ for reaction. After completion of the extraction with ethyl acetate (3×5.0 mL), the organic layers were combined, dried over anhydrous magnesium sulfate, and the solvent was concentrated under reduced pressure to give a crude product. The crude product was purified by silica gel chromatography using a mixture of ethyl acetate/petroleum ether (1/20) as eluent to give the pure product in 90% yield.
The structural characterization data of the product obtained in example 7 are shown below:
colorless oil, 1 H NMR(400MHz,CDCl 3 )δ7.47(d,J＝7.9Hz,2H),7.41-7.36(m,4H),6.94(t,J＝7.3Hz,1H),6.82(d,J＝8.3Hz,2H),4.45(s,2H),4.13(s,1H),2.57(s,3H)；
13 C NMR(101MHz,CDCl 3 )δ148.5,137.0,136.6,129.5,129.5,127.7,117.7,113.1,48.2,21.4.
the structure of the resulting product is deduced from the above data as follows:
example 8 preparation of N- (4-fluorobenzyl) aniline from 4-fluorobenzyl alcohol and aniline
In a 10mL Schlenk tube, 4-fluorobenzyl alcohol (1.1 mmol), aniline (1.0 mmol), KOH (1.1 mmol), H were added 2 O (2.0 mL) and chloromono [2- (4, 5-dihydro-1H-imidazol-2-yl) -6-methoxypyridine]PentamethylcyclopentadienylIridium (III) (0.1 mol%). Under the protection of nitrogen, heating to 80 ℃ for reaction. After completion of the extraction with ethyl acetate (3×5.0 mL), the organic layers were combined, dried over anhydrous magnesium sulfate, and the solvent was concentrated under reduced pressure to give a crude product. The crude product was purified by silica gel chromatography using a mixture of ethyl acetate/petroleum ether (1/20) as eluent to give the pure product in 91% yield.
The structural characterization data of the product obtained in example 8 are shown below:
colorless oil, 1 H NMR(400MHz,CDCl 3 )δ7.46(dd,J＝8.5,5.5Hz,2H),7.35(dd,J＝8.3,7.5Hz,2H),7.18(t,J＝8.7Hz,2H),6.91(t,J＝7.3Hz,1H),6.77(d,J＝7.8Hz,2H),4.41(s,2H),4.13(s,1H)；
13 C NMR(101MHz,CDCl 3 )δ163.4,161.0,148.2,135.4,135.4,129.5,129.2,129.1,117.9,115.7,115.5,113.1,47.7.
the structure of the resulting product is deduced from the above data as follows:
EXAMPLE 9 preparation of N-benzyl-4-chloroaniline from benzyl alcohol and 4-chloroaniline
Into a 10mL Schlenk tube, benzyl alcohol (1.1 mmol), 4-chloroaniline (1.0 mmol), KOH (1.1 mmol), H were added 2 O (2.0 mL) and chloromono [2- (4, 5-dihydro-1H-imidazol-2-yl) -6-methoxypyridine](pentamethylcyclopentadienyl) iridium (III) (0.1 mol%). Under the protection of nitrogen, heating to 80 ℃ for reaction. After completion of the extraction with ethyl acetate (3×5.0 mL), the organic layers were combined, dried over anhydrous magnesium sulfate, and the solvent was concentrated under reduced pressure to give a crude product. The crude product was purified by silica gel chromatography using a mixture of ethyl acetate/petroleum ether (1/20) as eluent to give the pure product in 90% yield.
The structural characterization data of the product obtained in example 9 are shown below:
colorless oil, 1 H NMR(400MHz,CDCl 3 )δ7.52-7.38(m,5H),7.23(d,J＝8.8Hz,2H),6.63(d,J＝8.8Hz,2H),4.37(s,2H),4.12(s,1H)；
13 C NMR(101MHz,CDCl 3 )δ146.8,139.1,129.2,128.9,127.6,127.5,122.1,114.1,48.4.
the structure of the resulting product is deduced from the above data as follows:
EXAMPLE 10 preparation of N-benzyl-4-fluoroaniline from benzyl alcohol and 4-fluoroaniline
Into a 10mL Schlenk tube, benzyl alcohol (1.1 mmol), 4-fluoroaniline (1.0 mmol), KOH (1.1 mmol), H were added 2 O (2.0 mL) and chloromono [2- (4, 5-dihydro-1H-imidazol-2-yl) -6-methoxypyridine](pentamethylcyclopentadienyl) iridium (III) (0.1 mol%). Under the protection of nitrogen, heating to 80 ℃ for reaction. After completion of the extraction with ethyl acetate (3×5.0 mL), the organic layers were combined, dried over anhydrous magnesium sulfate, and the solvent was concentrated under reduced pressure to give a crude product. The crude product was purified by silica gel chromatography using a mixture of ethyl acetate/petroleum ether (1/20) as eluent to give the pure product in 86% yield.
The structural characterization data of the product obtained in example 10 are shown below:
colorless oil, 1 H NMR(400MHz,CDCl 3 )δ7.52-7.34(m,5H),6.99(t,J＝8.7Hz,2H),6.71-6.57(m,2H),4.37(s,2H),3.89(s,1H)；
13 C NMR(101MHz,CDCl 3 )δ157.1,154.8,144.6,144.6,139.4,128.8,127.52(d,J＝17.7Hz),115.9,115.7,113.76(d,J＝7.4Hz),49.0.
the structure of the resulting product is deduced from the above data as follows:
EXAMPLE 11 preparation of N-benzyl-2-methylaniline from benzyl alcohol and 2-methylaniline
At 10mLInto a Schlenk tube, benzyl alcohol (1.1 mmol), 2-methylaniline (1.0 mmol), KOH (1.1 mmol), H were added 2 O (2.0 mL) and chloromono [2- (4, 5-dihydro-1H-imidazol-2-yl) -6-methoxypyridine](pentamethylcyclopentadienyl) iridium (III) (0.1 mol%). Under the protection of nitrogen, heating to 80 ℃ for reaction. After completion of the extraction with ethyl acetate (3×5.0 mL), the organic layers were combined, dried over anhydrous magnesium sulfate, and the solvent was concentrated under reduced pressure to give a crude product. The crude product was purified by silica gel chromatography using a mixture of ethyl acetate/petroleum ether (1/20) as eluent to give the pure product in 88% yield.
The structural characterization data of the product obtained in example 11 are shown below:
colorless oil,Yield:173.5mg,88％. 1 H NMR(400MHz,CDCl 3 )δ7.59-7.53(m,4H),7.50-7.48(m,1H),7.30(dd,J＝12.9,7.1Hz,2H),6.89(t,J＝7.4Hz,1H),6.81(d,J＝8.0Hz,1H),4.55(s,2H),4.04(s,1H),2.36(s,3H)；
13 C NMR(101MHz,CDCl 3 )δ146.3,139.7,130.3,128.9,127.7,127.4,127.4,122.1,117.4,110.2,48.5,17.8.
the structure of the resulting product is deduced from the above data as follows:
EXAMPLE 12 preparation of N-benzyl-3-methylaniline from benzyl alcohol and 3-methylaniline
Into a 10mL Schlenk tube, benzyl alcohol (1.1 mmol), 3-methylaniline (1.0 mmol), KOH (1.1 mmol), H were added 2 O (2.0 mL) and chloromono [2- (4, 5-dihydro-1H-imidazol-2-yl) -6-methoxypyridine](pentamethylcyclopentadienyl) iridium (III) (0.1 mol%). Under the protection of nitrogen, heating to 80 ℃ for reaction. After completion of the extraction with ethyl acetate (3×5.0 mL), the organic layers were combined, dried over anhydrous magnesium sulfate, and the solvent was concentrated under reduced pressure to give a crude product. The crude product was purified by silica gel chromatography using a mixture of ethyl acetate/petroleum ether (1/20) as eluent to give the pure product in 90% yield.
The structural characterization data of the product obtained in example 12 are shown below:
colorless oil, 1 H NMR(400MHz,CDCl 3 )δ7.59-7.57(m,4H),7.53-7.46(m,1H),7.31(t,J＝7.7Hz,1H),6.81(d,J＝7.5Hz,1H),6.70–6.61(m,2H),4.50(s,2H),4.12(s,1H),2.52(s,3H)；
13 C NMR(101MHz,CDCl 3 )δ148.5,139.9,139.2,129.4,128.9,127.8,127.4,118.8,113.9,110.2,48.5,21.9.
the structure of the resulting product is deduced from the above data as follows:
EXAMPLE 13 preparation of N-benzyl-4-methyl-3-bromoaniline from benzyl alcohol and 4-methyl-3-bromoaniline
Into a 10mL Schlenk tube, benzyl alcohol (1.1 mmol), 4-methyl-3-bromoaniline (1.0 mmol), KOH (1.1 mmol), H were added 2 O (2.0 mL) and chloromono [2- (4, 5-dihydro-1H-imidazol-2-yl) -6-methoxypyridine](pentamethylcyclopentadienyl) iridium (III) (0.1 mol%). Under the protection of nitrogen, heating to 80 ℃ for reaction. After completion of the extraction with ethyl acetate (3×5.0 mL), the organic layers were combined, dried over anhydrous magnesium sulfate, and the solvent was concentrated under reduced pressure to give a crude product. The crude product was purified by silica gel chromatography using a mixture of ethyl acetate/petroleum ether (1/20) as eluent to give the pure product in 91% yield.
The structural characterization data of the product obtained in example 13 are shown below:
colorless oil, 1 H NMR(400MHz,CDCl 3 )δ7.39-7.28(m,5H),7.02(d,J＝8.2Hz,1H),6.88(d,J＝2.4Hz,1H),6.51(dd,J＝8.2,2.4Hz,1H),4.31(s,2H),2.29(s,3H)；
13 C NMR(101MHz,CDCl 3 )δ147.3,139.0,131.1 128.7,127.5,127.4,.1256.2,125.4,116.3,112.2,48.4,21.7.
the structure of the resulting product is deduced from the above data as follows:
EXAMPLE 14 preparation of N-benzyl-4-methoxyaniline from benzyl alcohol and 4-methoxyaniline
Into a 10mL Schlenk tube, benzyl alcohol (1.1 mmol), 4-methoxyaniline (1.0 mmol), KOH (1.1 mmol), H were added 2 O (2.0 mL) and chloromono [2- (4, 5-dihydro-1H-imidazol-2-yl) -6-methoxypyridine](pentamethylcyclopentadienyl) iridium (III) (0.1 mol%). Under the protection of nitrogen, heating to 80 ℃ for reaction. After completion of the extraction with ethyl acetate (3×5.0 mL), the organic layers were combined, dried over anhydrous magnesium sulfate, and the solvent was concentrated under reduced pressure to give a crude product. The crude product was purified by silica gel chromatography using a mixture of ethyl acetate/petroleum ether (1/20) as eluent to give the pure product in 93% yield.
The structural characterization data of the product obtained in example 14 are shown below:
colorless oil, 1 H NMR(400MHz,CDCl 3 )δ7.50-7.44(m,4H),7.41-7.40(m,1H),6.91(d,J＝8.9Hz,2H),6.71(d,J＝8.9Hz,2H),4.38(s,2H),3.84(s,3H)；
13 C NMR(101MHz,CDCl 3 )δ152.3,142.6,139.9,128.7),127.7,127.3,115.0,114.2,55.9,49.3.
the structure of the resulting product is deduced from the above data as follows:
EXAMPLE 15 preparation of N- (1-phenethyl) aniline from phenethyl alcohol and aniline
Into a 10mL Schlenk tube, phenethyl alcohol (1.1 mmol), aniline (1.0 mmol), KOH (1.1 mmol), H were added 2 O (2.0 mL) and chloromono [2- (4, 5-dihydro-1H-imidazol-2-yl) -6-methoxypyridine](pentamethylcyclopentadienyl) iridium (III) (0.1 mol%). Under the protection of nitrogen, heating to 80 ℃ for reaction. After completion, extraction with ethyl acetate (3X 5.0 mL)The organic layers were combined, dried over anhydrous magnesium sulfate, and the solvent was concentrated under reduced pressure to give a crude product. The crude product was purified by silica gel chromatography using a mixture of ethyl acetate/petroleum ether (1/20) as eluent to give N- (1-phenethyl) aniline in 94% yield.
The structural characterization data of the product obtained in example 15 are shown below:
colorless oil, 1 H NMR(400MHz,CDCl 3 )δ7.47-7.34(m,4H),7.31-7.27(m,1H),7.16(t,J＝7.8Hz,2H),6.71(t,J＝7.3Hz,1H),6.58(d,J＝8.1Hz,2H),4.55(q,J＝6.7Hz,1H),4.09(s,1H),1.58(d,J＝6.7Hz,3H)；
13 C NMR(101MHz,CDCl 3 )δ147.3,145.3,129.2,128.7,126.9,125.9,117.3,113.3,53.5,25.1.
the structure of the resulting product is deduced from the above data as follows:
EXAMPLE 16 preparation of N- [1- (3, 4-dichlorophenyl) ethyl ] aniline from 3, 4-dichlorophenyl ethanol and 4-methylaniline
Into a 10mL Schlenk tube, 3, 4-dichlorophenyl ethanol (1.1 mmol), 4-methylaniline (1.0 mmol), KOH (1.1 mmol), H were added 2 O (2.0 mL) and chloromono [2- (4, 5-dihydro-1H-imidazol-2-yl) -6-methoxypyridine](pentamethylcyclopentadienyl) iridium (III) (0.1 mol%). Under the protection of nitrogen, heating to 80 ℃ for reaction. After completion of the extraction with ethyl acetate (3×5.0 mL), the organic layers were combined, dried over anhydrous magnesium sulfate, and the solvent was concentrated under reduced pressure to give a crude product. The crude product was purified by silica gel chromatography using a mixture of ethyl acetate/petroleum ether (1/20) as eluent to give N- (1-phenethyl) aniline in 92% yield.
The structural characterization data of the product obtained in example 16 are shown below:
colorless oil, 1 H NMR(400MHz,CDCl 3 )δ7.49(d,J＝2.0Hz,1H),7.40(d,J＝8.3Hz,1H),7.23(dd,J＝8.3,2.0Hz,1H),6.94(d,J＝8.3Hz,2H),6.41(d,J＝8.4Hz,2H),4.41(q,J＝6.7Hz,1H),2.22(s,3H),1.50(d,J＝6.7Hz,3H)；
13 C NMR(101MHz,CDCl 3 )δ146.1,144.4,132.7,130.7,130.6,129.7,127.9,127.0,125.3,113.4,53.1,25.1,20.4.HRMS-ESI(m/z):calcd for C 15 H 16 NCl 2 ,[M+H] + :280.0660,found 280.0658.
the structure of the resulting product is deduced from the above data as follows:
EXAMPLE 17 preparation of N- (2-naphthylmethyl) aniline from 2-naphthylmethanol and aniline
In a 10mL Schlenk tube, 2-naphthalenyl alcohol (1.1 mmol), aniline (1.0 mmol), KOH (1.1 mmol), H were added 2 O (2.0 mL) and chloromono [2- (4, 5-dihydro-1H-imidazol-2-yl) -6-methoxypyridine](pentamethylcyclopentadienyl) iridium (III) (0.1 mol%). Under the protection of nitrogen, heating to 80 ℃ for reaction. After completion of the extraction with ethyl acetate (3×5.0 mL), the organic layers were combined, dried over anhydrous magnesium sulfate, and the solvent was concentrated under reduced pressure to give a crude product. The crude product was purified by silica gel chromatography using a mixture of ethyl acetate/petroleum ether (1/20) as eluent to give the pure product in 96% yield.
The structural characterization data of the product obtained in example 17 are shown below:
white solid,mp 55-56℃. 1 H NMR(400MHz,CDCl 3 )δ8.05-7.89(m,4H),7.66-.62(m,3H),7.40-7.36(m,2H),6.94(t,J＝7.3Hz,1H),6.86-6.75(m,2H),4.58(s,2H),4.20(s,1H)；
13 C NMR(101MHz,CDCl 3 )δ148.4,137.21(s),133.7,133.0,129.5,128.6,128.0,127.9,126.4,126.1,126.0,117.8,113.1,48.6.
the structure of the resulting product is deduced from the above data as follows:
EXAMPLE 18 preparation of N- (1-naphthylmethyl) aniline from 1-naphthylmethanol and aniline
1-naphthalenyl alcohol (1.1 mmol), aniline (1.0 mmol), KOH (1.1 mmol), H were added to a 10mL Schlenk tube 2 O (2.0 mL) and chloromono [2- (4, 5-dihydro-1H-imidazol-2-yl) -6-methoxypyridine](pentamethylcyclopentadienyl) iridium (III) (0.1 mol%). Under the protection of nitrogen, heating to 80 ℃ for reaction. After completion of the extraction with ethyl acetate (3×5.0 mL), the organic layers were combined, dried over anhydrous magnesium sulfate, and the solvent was concentrated under reduced pressure to give a crude product. The crude product was purified by silica gel chromatography using a mixture of ethyl acetate/petroleum ether (1/20) as eluent to give the pure product in 94% yield.
The structural characterization data of the product obtained in example 18 are shown below:
grey solid, 1 H NMR(400MHz,CDCl 3 )δ8.32-8.21(m,1H),8.13-8.11(m,1H),8.03(d,J＝8.1Hz,1H),7.79-7.67(m,3H),7.67-7.59(m,1H),7.45(t,J＝7.8Hz,2H),7.02(t,J＝7.3Hz,1H),6.85(d,J＝8.3Hz,2H),4.86(s,2H),4.09(s,1H)；
13 C NMR(101MHz,CDCl 3 )δ148.5,134.7,134.2,131.8,129.6,129.1,128.41(s),126.6,126.2,126.1,125.9,123.9,117.8,113.0,46.5.
the structure of the resulting product is deduced from the above data as follows:
example 19 preparation of N- (2-thiophenemethyl) aniline from 2-thiophenemethanol and aniline
In a 10mL Schlenk tube, 2-thiophenecanol (1.1 mmol), aniline (1.0 mmol), KOH (1.1 mmol), H were added 2 O (2.0 mL) and chloromono [2- (4, 5-dihydro-1H-imidazol-2-yl) -6-methoxypyridine](pentamethylcyclopentadienyl) iridium (III) (0.1 mol%). Under the protection of nitrogen, heating to 80 ℃ for reaction. After completion, extract with ethyl acetate (3X 5.0 mL), combine organic layers with noDrying over magnesium sulfate, and concentrating the solvent under reduced pressure to obtain crude product. The crude product was purified by silica gel chromatography using a mixture of ethyl acetate/petroleum ether (1/50) as eluent to give the pure product in 89% yield.
The structural characterization data of the product obtained in example 19 are shown below:
colorless oil, 1 H NMR(400MHz,CDCl 3 )δ7.35-7.31(m,3H),7.16-7.05(m,2H),6.89(t,J＝7.3Hz,1H),6.79(d,J＝8.3Hz,2H),4.60(s,2H),4.13(s,1H)；
13 C NMR(101MHz,CDCl 3 )δ147.8,143.2,129.4,127.0,125.2,124.7,118.2,113.3,43.6.
the structure of the resulting product is deduced from the above data as follows:
EXAMPLE 20 preparation of N- (2-Fulmethyl) aniline from 2-furanmethanol and aniline
In a 10mL Schlenk tube, 2-furanmethanol (1.1 mmol), aniline (1.0 mmol), KOH (1.1 mmol), H were added 2 O (2.0 mL) and chloromono [2- (4, 5-dihydro-1H-imidazol-2-yl) -6-methoxypyridine](pentamethylcyclopentadienyl) iridium (III) (0.1 mol%). Under the protection of nitrogen, heating to 80 ℃ for reaction. After completion of the extraction with ethyl acetate (3×5.0 mL), the organic layers were combined, dried over anhydrous magnesium sulfate, and the solvent was concentrated under reduced pressure to give a crude product. The crude product was purified by silica gel chromatography using a mixture of ethyl acetate/petroleum ether (1/50) as eluent to give the pure product in 91% yield.
The structural characterization data of the product obtained in example 20 are shown below:
colorless oil, 1 H NMR(400MHz,CDCl 3 )δ7.44-7.43(m,1H),7.28-7.24(m,2H),6.82(t,J＝7.3Hz,1H),6.74(dd,J＝8.5,0.9Hz,2H),6.30-6.39(m,1H),6.31-6.30(m,1H),4.38(s,2H),4.08(s,1H)；
13 C NMR(101MHz,CDCl 3 )δ152.8,147.7,142.0,129.3,118.1,113.2,110.4,107.1,41.5.
the structure of the resulting product is deduced from the above data as follows:
EXAMPLE 21 preparation of N-butylaniline from butanol and aniline
In a 10mL Schlenk tube, n-butanol (1.1 mmol), aniline (1.0 mmol), KOH (1.1 mmol), H were added 2 O (2.0 mL) and chloromono [2- (4, 5-dihydro-1H-imidazol-2-yl) -6-methoxypyridine](pentamethylcyclopentadienyl) iridium (III) (0.1 mol%). Under the protection of nitrogen, heating to 80 ℃ for reaction. After completion of the extraction with ethyl acetate (3×5.0 mL), the organic layers were combined, dried over anhydrous magnesium sulfate, and the solvent was concentrated under reduced pressure to give a crude product. The crude product was purified by silica gel chromatography using a mixture of ethyl acetate/petroleum ether (1/50) as eluent to give the pure product in 93% yield.
The structural characterization data of the product obtained in example 21 are shown below:
colorless oil, 1 H NMR(400MHz,CDCl 3 )δ7.24(t,J＝7.8Hz,2H),6.75(t,J＝7.3Hz,1H),6.67(d,J＝8.3Hz,2H),3.64(s,1H),3.17(t,J＝7.1Hz,2H),1.72-1.61(m,2H),1.54-1.44(m,2H),1.03(t,J＝7.3Hz,3H)；
13 C NMR(101MHz,CDCl 3 )δ148.6,129.3,117.1,112.7,43.7,31.7,20.4,14.0.
the structure of the resulting product is deduced from the above data as follows:
EXAMPLE 22 preparation of N-cyclohexylaniline from cyclohexanol and aniline
Into a 10mL Schlenk tube, cyclohexanol (1.1 mmol), aniline (1.0 mmol), KOH (1.1 mmol), H were added 2 O (2.0 mL) and chloromono- (2- (4, 5-dihydro-1H-imidazol-2-yl) -6-methoxy)Pyridine compound](pentamethylcyclopentadienyl) iridium (III) (0.1 mol%). Under the protection of nitrogen, heating to 80 ℃ for reaction. After completion of the extraction with ethyl acetate (3×5.0 mL), the organic layers were combined, dried over anhydrous magnesium sulfate, and the solvent was concentrated under reduced pressure to give a crude product. The crude product was purified by silica gel chromatography using a mixture of ethyl acetate/petroleum ether (1/50) as eluent to give the pure product in 90% yield.
The structural characterization data of the product obtained in example 22 are shown below:
colorless oil, 1 H NMR(400MHz,CDCl 3 )δ7.33-7.19(m,2H),6.82-6.75(m,1H),6.70(dd,J＝8.6,1.0Hz,2H),3.61(s,1H),3.40-3.33(m,1H),2.18(dd,J＝12.9,3.2Hz,2H),1.95-1.82(m,2H),1.79-1.76(m,1H),1.54-1.44(m,2H),1.39-1.24(m,3H)；
13 C NMR(101MHz,CDCl 3 )δ147.5,129.4,116.9,113.3,51.8,336,26.1,25.2.
the structure of the resulting product is deduced from the above data as follows:
EXAMPLE 23 preparation of N-benzyl-N-ethylaniline from benzyl alcohol and aniline
Into a 10mL Schlenk tube, benzyl alcohol (1.1 mmol), N-ethylaniline (1.0 mmol), KOH (1.1 mmol), H were added 2 O (2.0 mL) and chloromono [2- (4, 5-dihydro-1H-imidazol-2-yl) -6-methoxypyridine](pentamethylcyclopentadienyl) iridium (III) (0.1 mol%). Under the protection of nitrogen, heating to 80 ℃ for reaction. After completion of the extraction with ethyl acetate (3×5.0 mL), the organic layers were combined, dried over anhydrous magnesium sulfate, and the solvent was concentrated under reduced pressure to give a crude product. The crude product was purified by silica gel chromatography using a mixture of ethyl acetate/petroleum ether (1/50) as eluent to give the pure product in 89% yield.
The structural characterization data of the product obtained in example 23 are shown below:
colorless oil, 1 H NMR(400MHz,CDCl 3 )δ7.43-7.30(m,7H),6.84-6.78(m,3H),4.64(s,2H),3.60(q,J＝7.0Hz,2H),1.33(t,J＝7.1Hz,3H)；
13 C NMR(101MHz,CDCl 3 )δ148.6,139.4,129.4,128.7,126.9,126.7,116.1,112.3,54.0,45.2,12.2.
the structure of the resulting product is deduced from the above data as follows:
EXAMPLE 24 preparation of N-benzyl-N' - (4-methoxyphenyl) piperidine from benzyl alcohol and N- (4-methoxyphenyl) piperidine
Into a 10mL Schlenk tube, benzyl alcohol (1.1 mmol), N- (4-methoxyphenyl) piperidine (1.0 mmol), KOH (1.1 mmol), H were added 2 O (2.0 mL) and chloromono [2- (4, 5-dihydro-1H-imidazol-2-yl) -6-methoxypyridine](pentamethylcyclopentadienyl) iridium (III) (0.1 mol%). Under the protection of nitrogen, heating to 80 ℃ for reaction. After completion of the extraction with ethyl acetate (3×5.0 mL), the organic layers were combined, dried over anhydrous magnesium sulfate, and the solvent was concentrated under reduced pressure to give a crude product. The crude product was purified by silica gel chromatography using a mixture of ethyl acetate/petroleum ether (1/50) as eluent to give the pure product in 91% yield.
The structural characterization data of the product obtained in example 24 are shown below:
colorless oil, 1 H NMR(400MHz,CDCl 3 )δ7.38(br,5H),7.35-7.30(m,2H),6.93-6.85(m,2H),4.68(s,3H),3.79(s,2H),3.60(s,1H),3.26-2.95(m,3H),2.67-2.42(m,4H)；
13 C NMR(101MHz,CDCl 3 )δ153.9,145.7,141.0,137.7,129.4,128.6,127.6,127.0,118.4,114.4,65.2,63.1,55.6,53.1,50.6.
the structure of the resulting product is deduced from the above data as follows:
the embodiments of the present invention have been described in detail in the above examples, but the present invention is not limited to the above embodiments, and various changes may be made without departing from the spirit of the present invention within the knowledge of one of ordinary skill in the art. The above description is only of the preferred embodiments of the present invention, and is not intended to limit the scope of the claims, but all equivalent structural changes made by the application of the present invention are included in the scope of the claims.
Claims (8)
1. The method for efficiently realizing the N-alkylation reaction by using the cycloiridium catalyst is characterized by comprising the following steps: taking an amine compound 2 and an alcohol compound 1 as raw materials, taking a cycloiridium complex as a catalyst, taking water as a reaction medium, heating and stirring for reaction for 12-24 hours under the protection of inert gas, and after the reaction is finished, obtaining a series of amine compounds 3 through post-treatment; the N-alkylation reaction is represented by the following formula:
wherein R is 1 3-chlorophenyl, 4-chlorophenyl, 2-methoxyphenyl, 3-methoxyphenyl, 4-fluorophenyl, 3, 4-dichlorophenyl, 4-methylphenyl, 1-naphthyl, 2-naphthyl, thienyl, furyl, n-butyl or cyclohexyl;
R 2 is methyl;
R 3 is one of ethyl, 2-methylphenyl, 3-methylphenyl, 4-methoxyphenyl, 4-chlorophenyl, 4-fluorophenyl, 4-methyl-3-bromophenyl or N- (4-methoxyphenyl) piperazinyl;
the cycloiridium complex is chloromono- (2- (4, 5-dihydro-1H-imidazol-2-yl) -6-methoxypyridine ] (pentamethylcyclopentadienyl) iridium (III) chloride.
2. The method for efficiently effecting an N-alkylation reaction with a cyclic iridium catalyst according to claim 1, wherein the inert gas is argon or helium.
3. The method for efficiently realizing the N-alkylation reaction by using the cycloiridium catalyst according to claim 1, wherein the molar ratio of the addition amount of the alcohol compound 1 to the addition amount of the amine compound 2 is 1-1.2: 1.
4. the method for efficiently realizing N-alkylation reaction by using a cycloiridium catalyst according to claim 1, wherein the molar ratio of the cycloiridium complex to the amine compound 2 is 0.01-0.1: 1.
5. the method for efficiently realizing an N-alkylation reaction by using a cycloiridium catalyst according to claim 1, wherein the N-alkylation reaction is performed under alkaline conditions, and the alkali is one of potassium tert-butoxide, sodium acetate, potassium acetate, sodium formate, potassium carbonate, sodium carbonate, potassium hydroxide or sodium hydroxide.
6. The method for efficiently realizing N-alkylation reaction by using a cycloiridium catalyst according to claim 5, wherein the molar ratio of the alkali to the alcohol compound 1 is 1-1.5: 1.
7. the method for efficiently realizing an N-alkylation reaction by using a cycloiridium catalyst according to claim 1, wherein the temperature of the heating and stirring reaction is 60 ℃ to 110 ℃.
8. The method for efficiently realizing N-alkylation reaction by using the cycloiridium catalyst according to claim 1, wherein after the reaction is finished, the method is cooled to room temperature, reduced pressure distillation and concentration are carried out to obtain a crude product, and a series of amine compounds 3 are obtained through column chromatography purification, wherein the column chromatography eluent is pure petroleum ether or mixed solvent; the mixed solvent is a mixed solvent of petroleum ether and ethyl acetate, wherein the volume ratio of petroleum ether to ethyl acetate is 10-50:1.
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