Nickel-catalyzed n-alkylation to prepare secondary amines or n′-alkylhydrazides

A technology of alkylation reaction and alkyl hydrazide, which is applied in the field of N-alkylation, can solve problems such as N'-alkylation of hydrazide compounds, save experimental steps and costs, and improve environmental friendliness performance, easy operation

Active Publication Date: 2019-09-24
SHANDONG NORMAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In addition, the N-alkylation reactions reported in the current literature and patents all use primary or secondary amines as raw materials, and there is no related report on the N'-alkylation of hydrazide compounds.

Method used

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  • Nickel-catalyzed n-alkylation to prepare secondary amines or n′-alkylhydrazides
  • Nickel-catalyzed n-alkylation to prepare secondary amines or n′-alkylhydrazides
  • Nickel-catalyzed n-alkylation to prepare secondary amines or n′-alkylhydrazides

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0048] Embodiment 1: Preparation of N-phenyl-1-phenyl-1-ethylamine

[0049]

[0050] Under nitrogen protection, add Ni(OTf) into a 10mL Schlenk reaction tube 2 (2.9mg, 0.008mmol), 1,2-bis(dicyclohexylphosphine)ethane (4.3mg, 0.010mmol) and tert-amyl alcohol (1.2mL), stirred for 10 minutes, then added aniline (38mg, 0.4mmol) , 1-phenylethanol (98mg, 0.8mmol) and Molecular sieves (100 mg). The reaction tube was sealed and heated in an oil bath at 120°C for 24 hours. After the reaction stopped, it was cooled, and the reaction solution was directly added to a silica gel column, and eluted with petroleum ether and ethyl acetate (volume ratio 20:1) to obtain pure N-phenyl-1-phenyl-1-ethylamine, the yield 80%.

[0051] 1 H NMR (400MHz, CDCl 3 ):δ7.41-7.33(m,2H),7.30-7.26(m,2H),7.24-7.18(m,1H),7.12-7.00(m,2H),6.63(m,1H),6.55-6.42 (m,2H),4.47(q,J=6.7Hz,1H),4.00(br s,1H),1.50(d,J=6.7Hz,3H).

[0052] 13 C NMR (101MHz, CDCl 3 ): δ147.3, 145.2, 129.1, 128.6, 126.8, 125.8, 117...

Embodiment 2

[0053] Embodiment 2: Preparation of N-(4-methylphenyl)-1-phenyl-1-ethylamine

[0054]

[0055] Under nitrogen protection, add Ni(OTf) into a 10mL Schlenk reaction tube 2 (2.9mg, 0.008mmol), 1,2-bis(dicyclohexylphosphine)ethane (4.3mg, 0.010mmol) and tert-amyl alcohol (1.2mL), stirred for 10 minutes, then added 4-methylaniline (43mg , 0.4mmol), 1-phenylethanol (98mg, 0.8mmol) and Molecular sieves (100 mg). The reaction tube was sealed and heated in an oil bath at 120°C for 24 hours. After the reaction stopped, it was cooled, and the reaction solution was directly added to a silica gel column, and eluted with petroleum ether and ethyl acetate (volume ratio 20:1) to obtain pure N-(4-methylphenyl)-1-phenyl-1 -Ethylamine, 90% yield.

[0056] 1 H NMR (400MHz, CDCl 3 ): δ7.36(d, J=7.2Hz, 2H), 7.30(t, J=7.1Hz, 2H), 7.23-7.21(m, 1H), 6.89(d, J=7.6Hz, 2H), 6.43 (d, J=7.7Hz, 2H), 4.45(q, J=6.3Hz, 1H), 3.90(s, 1H), 2.18(s, 1H), 1.49(d, J=6.3Hz, 3H).

[0057] 13 C NMR (101MHz,...

Embodiment 3

[0058] Example 3: Preparation of N-(3,5-dimethylphenyl)-1-phenyl-1-ethylamine

[0059]

[0060] Under nitrogen protection, add Ni(OTf) into a 10mL Schlenk reaction tube 2 (2.9mg, 0.008mmol), 1,2-bis(dicyclohexylphosphine)ethane (4.3mg, 0.010mmol) and tert-amyl alcohol (1.2mL), stirred for 10 minutes, then added 3,5-dimethyl Aniline (49mg, 0.4mmol), 1-phenylethanol (98mg, 0.8mmol) and Molecular sieves (100 mg). The reaction tube was sealed and heated in an oil bath at 150°C for 24 hours. After the reaction stopped, cooled, the reaction solution was directly added to the silica gel column, and eluted with petroleum ether and ethyl acetate (volume ratio 20:1) to obtain pure N-(3,5-dimethylphenyl)-1-benzene Base-1-ethylamine, yield 72%.

[0061] 1 H NMR (400MHz, CDCl 3 ): δ7.36(d, J=7.2Hz, 2H), 7.31(t, J=7.2Hz, 2H), 7.25-7.20(m, 1H), 6.31(s, 1H), 6.16(s, 2H) ,4.47(q,J=6.3Hz,1H),3.90(s,1H),2.16(s,6H),1.49(d,J=6.4Hz,3H).

[0062] 13 C NMR (101MHz, CDCl 3 ): δ147.5, 145...

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Abstract

The invention discloses a method for preparing secondary amine or N'-alkyl hydrazide through nickel catalysis N-alkylation reaction. Amine or hydrazide is used as raw materials; alcohol is used as an alkylation agent; N-alkylation reaction is performed under the nickel catalysis condition; the secondary amine or N'-alkyl hydrazide is prepared. Compared with the prior art, the method provided by the invention has the advantages that the N-alkylation reaction is performed; active catalysts can be generated in situ by nickel salt and phosphine ligands; the preparation of catalysts in advance is avoided; the operation is simple and convenient; the experiment steps and the experiment cost are reduced. Cheap nickel is used as the catalysts; the consumption of the catalysts is low; the use of expensive and high-toxicity precious metal is avoided; the experiment cost is further reduced; the hydrogen borrowing strategy is utilized; the N'-alkylation of the hydrazide is realized for the first time; byproducts only contain water. Compared with other preparation methods, the method has the advantage that the reaction environment-friendly performance is realized.

Description

technical field [0001] The invention relates to an N-alkylation method, in particular to a method for efficiently preparing secondary amines or N'-alkylhydrazides through a nickel-catalyzed alkylation reaction. Background technique [0002] Amines and hydrazides are widely used in the fields of medicine, pesticide and dye industry. The traditional method for the preparation of alkyl secondary amines or N'-alkylhydrazides is the alkylation of halogenated hydrocarbons with hydrazides. Although this method is simple to operate, the halogenated hydrocarbons are more toxic, and the hydrogen halide produced during the reaction is a strong acid, which needs to be absorbed by alkali. Another method is to condense amines with alkyl aldehydes and ketones to generate imines, and then undergo hydrogenation reactions to obtain alkyl secondary amines or N'-alkyl hydrazides. An improvement to this method is the reductive amination reaction of amines with aldehydes and ketones, avoiding t...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07C209/18C07C211/48C07C213/08C07C217/84C07C241/04C07C243/38C07D333/20
CPCC07C209/18C07C213/08C07C241/04C07D333/20C07C211/48C07C217/84C07C243/38
Inventor 唐波杨朋张彩莉马瑜张彩云李爱洁
Owner SHANDONG NORMAL UNIV
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