Method for visible light catalytic selective cyanation of piperazine compound

A technology for catalyzing piperazine and compounds, which is applied in the field of selective cyanation, can solve the problems of high cost of noble metals, high toxicity, unsuitability for selective cyanation of piperazine drug molecules, and high synthesis cost, and achieves the scope of substrate application. Wide, less catalyst dosage, easy to operate

Active Publication Date: 2017-10-03
SHAANXI NORMAL UNIV
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Traditional photocatalysts are generally complexes of ruthenium and iridium, coordinated by pyridine analogs. This type of catalyst has strong absorption under visible light, stable properties and a long life cycle, but it uses noble metals, and the synthesis cost high
For some common non-metallic organic dyes, the photocatalyst is also suitable for the cyanation reaction of amine compounds. Although it solves the problem of the cost and high toxicity of noble metals, these reaction systems are not suitable for complex piperazines. Selective cyanylation of drug molecules with very limited substrate coverage

Method used

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  • Method for visible light catalytic selective cyanation of piperazine compound
  • Method for visible light catalytic selective cyanation of piperazine compound
  • Method for visible light catalytic selective cyanation of piperazine compound

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0018] Preparation of 2-(4-phenylpiperazin-1-yl) valeronitrile of the following structural formula

[0019]

[0020] Multi-substituted BODIP-5 organic photocatalyst (1.80mg, 0.0025mmol), TMSCN (99mg, 1mmol), 1-butyl-4-phenylpiperazine (54mg, 0.25mmol), dichloromethane (3mL) were added to In the optical parallel reaction tube, turn on the 3W blue LED light, and stir the reaction at 30°C for 12 hours. After the reaction is completed, add 15 mL of saturated saline to the mixture, and then extract it three times with 15 mL of dichloromethane, collect the organic phase, and use Water Na 2 SO 4 Dry, filter with suction, remove the solvent with a rotary evaporator, and separate by column chromatography to obtain 47 mg of white solid 2-(4-phenylpiperazin-1-yl)valeronitrile, with a yield of 83%, and the characterization data are: 1 H NMR (400MHz, CDCl 3): δ7.22(t, J=8.0Hz, 2H), 6.88(t, J=8.4Hz, 2H), 6.82(t, J=7.2Hz, 1H), 3.50(t, J=8.0Hz, 1H ),3.23-3.12(m,4H),2.83-2.78(m,2H),2.61...

Embodiment 2

[0030] Preparation of 2-(4-(p-tolyl)piperazin-1-yl)valeronitrile of the following structural formula

[0031]

[0032] In the present embodiment, replace the 1-butyl-4-phenylpiperazine in embodiment 1 with the 1-butyl-4-(p-tolyl) piperazine of equimolar amount, the reaction time is extended to 15 hours, other The procedure was the same as in Example 1 to obtain 40 mg of white solid 2-(4-(p-tolyl)piperazin-1-yl)valeronitrile with a yield of 61%, and the characteristic data were: 1 H NMR (400MHz, CDCl 3 ): δ7.08(d, J=8.0Hz, 2H), 6.84(d, J=8.4Hz, 2H), 3.55(t, J=7.2Hz, 1H), 3.53-3.12(m, 4H), 2.88 -2.82(m,2H),2.66-2.61(m,2H),2.27(s,3H),1.82-1.74(m,2H),1.57-1.50(m,2H),0.98(t,J=7.2Hz ,3H)ppm; 13 C NMR (100MHz, CDCl 3 ): δ149.1, 129.79, 129.73, 117.1, 116.7, 57.7, 49.8, 49.7, 33.0, 20.5, 19.4, 13.5ppm; HRMS (m / z, ESI) theoretical value C 16 h 23 N 3 Na + [M+Na] + : 280.1790, the measured value is 280.1789.

Embodiment 3

[0034] Preparation of 2-(4-(2-methoxyphenyl)piperazin-1-yl)valeronitrile of the following structural formula

[0035]

[0036] In this example, replace 1-butyl-4-phenylpiperazine in Example 1 with equimolar amounts of 1-butyl-4-(2-methoxyphenyl)piperazine, other steps and implementation Same as Example 1, 50 mg of yellow oily matter 2-(4-(2-methoxyphenyl) piperazin-1-yl) valeronitrile was obtained, the yield was 73%, and the characterization data were: 1 H NMR (400MHz, CDCl 3 ):δ7.02-6.97(m,1H),6.91(d,J=4.4Hz,2H),6.87(d,J=8.0Hz,1H),3.86(s,3H),3.54(t,J= 7.6Hz,1H),3.12(s,4H),2.91-2.86(m,2H),2.70-2.65(m,2H),1.87-1.71(m,2H),1.62-1.45(m,2H),0.98 (t,J=7.2Hz,3H)ppm; 13 C NMR (100MHz, CDCl 3 ): δ152.4, 141.1, 123.18, 121.11, 118.3, 117.3, 111.6, 57.7, 55.5, 50.4, 50.0, 33.0, 19.4, 13.5ppm; HRMS (m / z, ESI) theoretical value C 16 h 23 N 3 NaO + [M+Na] + : 296.1739, the measured value is 296.1734.

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Abstract

The invention discloses a method for visible light catalytic selective cyanation of a piperazine compound. The method comprises that a piperazine compound, trimethylsilyl cyanide and a multi-substituted BODIPY organic photocatalyst are stirred and undergo a reaction in the air atmosphere under visible light irradiation at 10 to 40 DEG C to produce a cyanopiperazine compound. Compared with the prior art, the method utilizes a small amount of a catalyst, is easy to operate, is environmentally friendly, needs mild reaction conditions, is fast and efficient, has a wide substrate application range, can selectively produce a cyanation product having a single structure and has a high conversion rate and selectivity. The catalyst system is suitable for selective cyanation of complex drug molecules.

Description

technical field [0001] The invention relates to a method for selective cyanation of piperazine compounds and derivatives thereof by using multi-substituted BODIPY organic photocatalysts under visible light irradiation conditions. Background technique [0002] Among the nitrogen-containing heterocycles, piperazine is one of the very important saturated heterocycles, which often appear in small molecules of clinical drugs. However, due to its special structure, compared with the common pyrrolidine and piperidine systems, the presence of the second nitrogen atom in the piperazine ring will cause various side reactions or inhibit or reduce the reactivity of the C-H bond. Therefore, there are fewer types of functionalized piperazine molecules, which limits the application prospects of this class of drugs in medicine. As the cyano group of the best modification group, the cyanamide compound obtained by reacting with nitrogen-containing heterocycle is a very important intermediate...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D295/15C07D295/155C07D213/74C07D239/42C07D295/205C07D241/04C07D401/12C07D401/04B01J31/02
Inventor 薛东禹婷
Owner SHAANXI NORMAL UNIV
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