Preparation method of substituted primary amine

Abstract

A preparation method of substituted primary amine is disclosed. The preparation method uses cyanophenyl and a derivative thereof as raw materials, nanoporous palladium as a catalyst, and H.sub.2 as a hydrogen source, and conducts selective hydrogenation to prepare the substituted primary amine. The molar concentration of the cyanophenyl and the derivative thereof in the solvent is 0.01-2 mmol/mL, and the molar ratio of the cyanophenyl to the derivative thereof to the catalyst is 1:0.01-1:0.5. The size of a pore framework of the nanoporous palladium is 1 nm-50 nm. The pressure of the H.sub.2 is 0.1-20.0 MPa. The obtained product has high selectivity; the present invention has mild reaction conditions, does not need any additive, and has simple operation and post-processing and good catalyst reproducibility. After repeatedly used, the catalytic activity of the present invention is not significantly reduced, thereby providing the possibility of realizing industrialization.

Claims

1. A method for preparing a substituted primary amine comprising: hydrogenating a cyanophenyl or cyanoalkyl raw materials in the presence of an unsupported nanoporous palladium catalyst, and H.sub.2 as a hydrogen source; and conducting selective hydrogenation to prepare the substituted primary amine, wherein a synthetic route is shown as follows: ##STR00012## reaction temperature is 0° C.-150° C., and reaction time is 12 h-36 h; R is aryl or alkyl; the solvent is one or a mixture of more than one of water, ether, acetonitrile, dimethyl sulfoxide, dioxane, triethylamine, tetrahydrofuran, toluene, ethanol, isopropanol, chloroform, methylene chloride, acetone and N,N-dimethylformamide, wherein a molar concentration of the cyanophenyl or cyanoalkyl in the solvent is 0.01-2 mmol/mL, and the molar ratio of the cyanophenyl or cyanoalkyl to the catalyst is 1:0.01-1:0.5.

2. The method for preparing the substituted primary amine according to claim 1, wherein a size of a pore framework of the unsupported nanoporous palladium is 1 nm-50 nm.

3. The method for preparing the substituted primary amine according to claim 1, wherein a pressure of the H.sub.2 is 0.1-20.0 MPa.

Description

DESCRIPTION OF DRAWINGS

(1) FIG. 1 is a .sup.1H NMR spectrum diagram of benzylamine in embodiments 1 and 2.

(2) FIG. 2 is a .sup.1H NMR spectrum diagram of 4-methylbenzylamine in embodiments 3 and 4.

(3) FIG. 3 is a .sup.1H NMR spectrum diagram of phenethylamine in embodiments 5 and 6.

(4) FIG. 4 is a .sup.1H NMR spectrum diagram of 4-methoxyphenethylamine in embodiments 7 and 8.

(5) FIG. 5 is a .sup.1H NMR spectrum diagram of n-hexylamine in embodiments 9 and 10.

DETAILED DESCRIPTION

(6) Specific embodiments of the present invention are further described below in combination with accompanying drawings and the technical solution.

(7) The preparation method of the substituted primary aliphatic amine in the present invention has highest selectivity and reaction yield of 100% and 93% respectively, and does not need any additive in the reaction. The selected catalyst has good catalytic reaction reproducibility and simple operation and post-processing. After repeatedly used, the catalytic activity of the catalyst is not significantly reduced, thereby providing favorable conditions for the industrial production.

Embodiment 1: Synthesis of Benzylamine

(8) A substrate benzonitrile (51.6 mg, 0.5 mmol) and hydrogen (5 bar) are added to an ethanol (3 mL) solvent with PdNPore (1.6 mg, 3 mol %) catalyst; the mixture is placed in an oil bath at 50° C. to react for 24 h; column chromatography is conducted (silica gel, 200-300 meshes; developing agent, methanol and ethyl acetate) to obtain 48.8 mg of benzylamine, with yield of 93% and selectivity of 97%. Under the same conditions, if Pd/C is used as the catalyst, the yield of the benzylamine is only 65%, and the selectivity is 72%.

(9) ##STR00002##

(10) .sup.1H NMR (400 MHz, CDCl.sub.3) δ: 7.35-7.20 (m, 5H), 3.84 (s, 2H), 1.54 (br, 2H).

Embodiment 2: Synthesis of Benzylamine

(11) A substrate benzonitrile (30.9 mg, 0.3 mmol) and hydrogen (5 bar) are added to an N,N-dimethylformamide (3 mL) solvent with PdNPore (5.4 mg, 10 mol %) catalyst; the mixture is placed in an oil bath at 30° C. to react for 20 h; column chromatography is conducted (silica gel, 200-300 meshes; developing agent, methanol and ethyl acetate) to obtain 28.9 mg of benzylamine, with yield of 90% and selectivity of 96%.

(12) ##STR00003##

(13) .sup.1H NMR (400 MHz, CDCl.sub.3) δ: 7.35-7.20 (m, 5H), 3.84 (s, 2H), 1.54 (br, 2H).

Embodiment 3: Synthesis of 4-methylbenzylamine

(14) A substrate 4-methylbenzonitrile (58.6 mg, 0.5 mmol) and hydrogen (5 bar) are added to an ethanol (3 mL) solvent with PdNPore (1.6 mg, 3 mol %) catalyst; the mixture is placed in an oil bath at 50° C. to react for 24 h; column chromatography is conducted (silica gel, 200-300 meshes; developing agent, methanol and ethyl acetate) to obtain 53.9 mg of 4-methylbenzylamine, with yield of 89% and selectivity of 98%. Under the same conditions, if Pd/C is used as the catalyst, the yield of the 4-methylbenzylamine is only 69%, and the selectivity is 78%.

(15) ##STR00004##

(16) .sup.1H NMR (CDCl.sub.3, 400 MHz) δ: 7.20 (d, J=8 Hz, 2H), 7.14 (d, J=8 Hz, 2H), 3.83 (s, 2H), 2.34 (s, 3H), 2.06 (br, 2H).

Embodiment 4: Synthesis of 4-methylbenzylamine

(17) A substrate 4-methylbenzonitrile (58.6 mg, 0.5 mmol) and hydrogen (5 bar) are added to an acetonitrile (5 mL) solvent with PdNPore (1.1 mg, 2 mol %) catalyst; the mixture is placed in an oil bath at 50° C. to react for 24 h; column chromatography is conducted (silica gel, 200-300 meshes; developing agent, methanol and ethyl acetate) to obtain 50.3 mg of 4-methylbenzylamine, with yield of 83% and selectivity of 96%.

(18) ##STR00005##

(19) .sup.1H NMR (CDCl.sub.3, 400 MHz) δ: 7.20 (d, J=8 Hz, 2H), 7.14 (d, J=8 Hz, 2H), 3.83 (s, 2H), 2.34 (s, 3H), 2.06 (br, 2H).

Embodiment 5: Synthesis of Phenethylamine

(20) A substrate phenylacetonitrile (58.58 mg, 0.5 mmol) and hydrogen (5 bar) are added to an ethanol (3 mL) solvent with PdNPore (1.6 mg, 3 mol %) catalyst; the mixture is placed in an oil bath at 70° C. to react for 24 h; column chromatography is conducted (silica gel, 200-300 meshes; developing agent, methanol and ethyl acetate) to obtain 53.3 mg of phenethylamine, with yield of 88% and selectivity of 100%. Under the same conditions, if Pd/C is used as the catalyst, the yield of the phenethylamine is only 40%, and the selectivity is 45%.

(21) ##STR00006##

(22) .sup.1H NMR (400 MHz, CDCl.sub.3) δ: 7.29-7.24 (m, 2H), 7.21-7.14 (m, 3H), 2.89 (t, J=7.2 Hz, 2H), 2.78 (t, J=7.2 Hz, 2H), 1.59 (br, 2H).

Embodiment 6: Synthesis of Phenethylamine

(23) A substrate phenylacetonitrile (58.58 mg, 0.5 mmol) and hydrogen (5 bar) are added to an ethanol (5 mL) solvent with PdNPore (2.7 mg, 5 mol %) catalyst; the mixture is placed in an oil bath at 70° C. to react for 19 h; column chromatography is conducted (silica gel, 200-300 meshes; developing agent, methanol and ethyl acetate) to obtain 52.71 mg of phenethylamine, with yield of 87% and selectivity of 100%.

(24) ##STR00007##

(25) .sup.1H NMR (400 MHz, CDCl.sub.3) δ: 7.29-7.24 (m, 2H), 7.21-7.14 (m, 3H), 2.89 (t, J=7.2 Hz, 2H), 2.78 (t, J=7.2 Hz, 2H), 1.59 (br, 2H).

Embodiment 7: Synthesis of 4-Methoxyphenethylamine

(26) A substrate 4-methoxybenzeneacetonitrile (73.59 mg, 0.5 mmol) and hydrogen (5 bar) are added to an ethanol (3 mL) solvent with PdNPore (1.6 mg, 3 mol %) catalyst; the mixture is placed in an oil bath at 70° C. to react for 24 h; column chromatography is conducted (silica gel, 200-300 meshes; developing agent, methanol and ethyl acetate) to obtain 62.8 mg of 4-methoxyphenethylamine, with yield of 83% and selectivity of 100%.

(27) ##STR00008##

(28) .sup.1H NMR (400 MHz, CDCl.sub.3) δ: 7.06 (d, J=8 Hz, 2H), 6.80 (d, J=8 Hz, 2H), 3.77 (s, 3H), 2.84 (t, J=8 Hz, 2H), 2.71 (t, J=8 Hz, 2H).

Embodiment 8: Synthesis of 4-methoxyphenethylamine

(29) A substrate 4-methoxybenzeneacetonitrile (73.59 mg, 0.5 mmol) and hydrogen (5 bar) are added to an acetonitrile (5 mL) solvent with PdNPore (2.7 mg, 5 mol %) catalyst; the mixture is placed in an oil bath at 50° C. to react for 16 h; column chromatography is conducted (silica gel, 200-300 meshes; developing agent, methanol and ethyl acetate) to obtain 60.48 mg of 4-methoxyphenethylamine, with yield of 80% and selectivity of 98%.

(30) ##STR00009##

(31) .sup.1H NMR (400 MHz, CDCl.sub.3) δ: 7.06 (d, J=8 Hz, 2H), 6.80 (d, J=8 Hz, 2H), 3.77 (s, 3H), 2.84 (t, J=8 Hz, 2H), 2.71 (t, J=8 Hz, 2H).

Embodiment 9: Synthesis of n-hexylamine

(32) A substrate hexanenitrile (48.58 mg, 0.5 mmol) and hydrogen (5 bar) are added to an ethanol (3 mL) solvent with PdNPore (1.6 mg, 3 mol %) catalyst; the mixture is placed in an oil bath at 50° C. to react for 24 h; column chromatography is conducted (silica gel, 200-300 meshes; developing agent, methanol and ethyl acetate) to obtain 44.0 mg of n-hexylamine, with yield of 87% and selectivity of 100%.

(33) ##STR00010##

(34) .sup.1H NMR (400 MHz, CDCl.sub.3) δ: 2.60 (t, J=7.2 Hz, 2H), 1.77 (br, 2H), 1.52-1.46 (m, 2H), 1.36-1.28 (m, 6H), 0.88 (t, J=6.8 Hz, 3H).

Embodiment 10: Synthesis of n-hexylamine

(35) A substrate hexanenitrile (48.58 mg, 0.5 mmol) and hydrogen (6 bar) are added to an ethanol (3 mL) solvent with PdNPore (2.7 mg, 5 mol %) catalyst; the mixture is placed in an oil bath at 80° C. to react for 20 h; column chromatography is conducted (silica gel, 200-300 meshes; developing agent, methanol and ethyl acetate) to obtain 45.54 mg of n-hexylamine, with yield of 90% and selectivity of 100%.

(36) ##STR00011##

(37) .sup.1H NMR (400 MHz, CDC.sub.3) δ: 2.60 (t, J=7.2 Hz, 2H), 1.77 (br, 2H), 1.52-1.46 (m, 2H), 1.36-1.28 (m, 6H), 0.88 (t, J=6.8 Hz, 3H).