Innovative Comprehensive Experimental Design of Organic Chemistry-Synthesis of 3，5-Diarylpyridine in Deep Eutectic Solvent

doi:10.19894/j.issn.1000-0518.240297

Chinese Journal of Applied Chemistry ›› 2025, Vol. 42 ›› Issue (6): 864-874.DOI: 10.19894/j.issn.1000-0518.240297

• Chemistry Teaching and Experiment Innovation • Previous Articles

Innovative Comprehensive Experimental Design of Organic Chemistry-Synthesis of 3，5-Diarylpyridine in Deep Eutectic Solvent

Hao YAN¹(), Zhuo-Ran SUN², Xiao-Rong LI¹

^1.College of Pharmacy，Shaanxi University of Chinese Medicine，Xianyang 712046，China
^2.Department of Clinical Medicine，Second College of Clinical Medicine，Shaanxi University of Chinese Medicine，Xianyang 712046，China

Received:2024-09-13 Accepted:2025-05-07 Published:2025-06-01 Online:2025-07-01
Contact: Hao YAN
About author:yanhao@sntcm.edu.cn
Supported by:
the Teaching Reform Project of Shaanxi University of Chinese Medicine(21jg23);the National Natural Science Foundation of China(82304893);the Key Research and Development Program of Shaanxi(2023-YBSF-278);the Key Research and Development Program of Xianyang(L2022ZDYFSF054)

Abstract

Abstract:

The deep eutectic solvents are applied to the synthesis of 3，5-diarylpyridine from abnormal Chichibabin pyridine reaction. The deep eutectic solvents are used as catalyst/solvent， which are cheap and easy to obtain， simple to prepare and have good biodegradability. The traditional organic solvent media is improved to a green and environmentally friendly reaction in deep eutectic solvents， which makes the reaction simpler and environmentally friendly. Meanwhile， the reaction conditions are optimized， the influence of different substituents on the reaction yield is also explored， which provides an innovative teaching scheme for the synthesis of 3，5-diarylpyridine from Chichibabin pyridine. The experimental process not only involves the basic experimental operations such as extraction， concentration， and column chromatography but also includes the preparation of deep eutectic solvents， infrared spectroscopy characterization， thermal stability test， melting point determination of the product， nuclear magnetic resonance， and mass spectrometry to characterize structure. At the same time， it also infiltrates the thinking of green chemistry， which is helpful to cultivate students' innovative ability and improve their comprehensive ability.

Key words: Deep eutectic solvents, Chichibabin pyridine synthesis, 3，5-Diarylpyridine, Innovative comprehensive experiment design

CLC Number:

O626.3

Hao YAN, Zhuo-Ran SUN, Xiao-Rong LI. Innovative Comprehensive Experimental Design of Organic Chemistry-Synthesis of 3，5-Diarylpyridine in Deep Eutectic Solvent[J]. Chinese Journal of Applied Chemistry, 2025, 42(6): 864-874.

Figures/Tables 15

Fig.1 Examples of compounds containing pyridine skeleton

Fig.2 Synthesis methods of pyridine skeleton construction

Fig.3 Formation of deep eutectic solvent n（ChCl）∶n（Urea）=1∶2

Fig.4 Synthetic route of 3，5-diphenylpyridine

Fig.5 Reaction mechanism of 3，5-diphenylpyridine from Chichibabin pyridine synthesis

Fig.6 FT-IR spectrum of ChCl/2Urea

Fig.7 TG and DTG curve of ChCl/2Urea

Table 1 The effect of different reaction temperatures on the yield of 3，5-diphenylpyridine

Entry	n（phenylacetaldehyde）/mmol	n（ammonium acetate）/mmol	V（ChCl/2Urea）/mL	Temperature/℃	Time/h	Yield/%
1	1.0	1.2	2.5	80	1	37.3
2	1.0	1.2	2.5	90	1	45.5
3	1.0	1.2	2.5	100	1	61.7
4	1.0	1.2	2.5	110	1	62.4
5	1.0	1.2	2.5	120	1	62.8

Table 2 The effect of different reaction time on the yield of 3，5-diphenylpyridine

Entry	n（phenylacetaldehyde）/mmol	n（ammonium acetate）/mmol	V（ChCl/2Urea）/mL	Temperature/℃	Time/h	Yield/%
1	1.0	1.2	2.5	100	0.5	38.7
2	1.0	1.2	2.5	100	1	61.7
3	1.0	1.2	2.5	100	1.5	62.0
4	1.0	1.2	2.5	100	2	60.6
5	1.0	1.2	2.5	100	2.5	58.9

Table 3 The effect of feeding ratio of reactants on the yield of 3，5-diphenylpyridine

Entry	n（phenylacetaldehyde）/mmol	n（ammonium）/mmol	V（ChCl/2Urea）/mL	Temperature/℃	Time/h	Yield/%
1	1.0	0.5	2.5	100	1	55.5
2	1.0	1.0	2.5	100	1	56.9
3	1.0	1.2	2.5	100	1	61.7
4	1.0	1.5	2.5	100	1	60.3
5	1.0	2	2.5	100	1	59.8

Table 4 Comparison between DESs method and traditional solvent methods

Entry	Synthetic method	Temperature/℃	Time/h	Yield/%
1	使用DMF传统溶剂法	100	1	20.6
2	使用DMF传统溶剂法	100	5	36.2
3	使用DMSO传统溶剂法	100	1	23.2
4	使用DMSO传统溶剂法	100	5	39.2
5	DESs	100	1	61.7

Fig.8 1H NMR spectrum of 3，5-diphenylpyridine

Fig.9 13C NMR spectrum of 3，5-diphenylpyridine

Fig.10 Mass spectrum of 3，5-diphenylpyridine

Fig.11 Expanded experiments on synthesis of 3，5-diphenylpyridine

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Innovative Comprehensive Experimental Design of Organic Chemistry-Synthesis of 3，5-Diarylpyridine in Deep Eutectic Solvent

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