An Efficient Synthesis of Arylated Pyridines from Conjugated Acetylenes and Substituted Benzylamines Catalyzed by Base

An efficient base-catalyzed synthesis of arylated pyridines has been disclosed. This reaction involving conjugated acetylenes and substituted benzylamines proceeded smoothly, giving rise to tri-aryl substituted pyridines which are biologically relevant compounds in good to excellent yields in N,N-dimethylformamide (DMF) under air at 140 °C with K2CO3 as catalyst.


General Conditions
All manipulations were performed under air.All reagents employed in the synthesis were analytical grade, purchased from J&K Scientific Ltd. (Shanghai, China) and used as received without any prior purification.The products were isolated by thin layer chromatography on silica gel using petroleum ether as the eluent. 1 H-NMR, 13 C-NMR spectra were recorded on a BrukerAvance III

General Conditions
All manipulations were performed under air.All reagents employed in the synthesis were analytical grade, purchased from J&K Scientific Ltd. (Shanghai, China) and used as received without any prior purification.The products were isolated by thin layer chromatography on silica gel using petroleum ether as the eluent. 1 H-NMR, 13 C-NMR spectra were recorded on a BrukerAvance III

General Conditions
All manipulations were performed under air.All reagents employed in the synthesis were analytical grade, purchased from J&K Scientific Ltd. (Shanghai, China) and used as received without any prior purification.The products were isolated by thin layer chromatography on silica gel using petroleum ether as the eluent. 1 H-NMR, 13 C-NMR spectra were recorded on a BrukerAvance III

General Conditions
All manipulations were performed under air.All reagents employed in the synthesis were analytical grade, purchased from J&K Scientific Ltd. (Shanghai, China) and used as received without any prior purification.The products were isolated by thin layer chromatography on silica gel using petroleum ether as the eluent. 1 H-NMR, 13 C-NMR spectra were recorded on a BrukerAvance III

General Conditions
All manipulations were performed under air.All reagents employed in the synthesis were analytical grade, purchased from J&K Scientific Ltd. (Shanghai, China) and used as received without any prior purification.The products were isolated by thin layer chromatography on silica gel using petroleum ether as the eluent. 1 H-NMR, 13 C-NMR spectra were recorded on a BrukerAvance III

General Conditions
All manipulations were performed under air.All reagents employed in the synthesis were analytical grade, purchased from J&K Scientific Ltd. (Shanghai, China) and used as received without any prior purification.The products were isolated by thin layer chromatography on silica gel using petroleum ether as the eluent. 1 H-NMR, 13 C-NMR spectra were recorded on a BrukerAvance III 3cfb 60 a Reaction conditions: conjugated acetylene (1a) (0.25 mmol), substituted benzylamine (2b) (2.0 mmol), K 2 CO 3 (0.5 mmol), DMF (0.5 mL), 140 • C, 10 h; b Isolated yield.

General Conditions
All manipulations were performed under air.All reagents employed in the synthesis were analytical grade, purchased from J&K Scientific Ltd. (Shanghai, China) and used as received without any prior purification.The products were isolated by thin layer chromatography on silica gel using petroleum ether as the eluent. 1 H-NMR, 13 C-NMR spectra were recorded on a Bruker Avance III (400 MHz, Bruker Corporation, Billerica, MA, USA) spectrometer using tetramethylsilane as the internal standard and CDCl 3 as the solvent.Chemical shift values are expressed in ppm relative to external TMS (see Supplementary).

General Procedure for the Preparation of Arylated Pyridines
1,4-Disubstituted-1,3-diacetylene (0.25 mmol) and K 2 CO 3 (0.5 mmol) were added, under air, to a solution of appropriate benzylamine (2.0 mmol) in DMSO (0.5 mL) previously heated at 140 • C. The resulting solution was stirred for 10 h at this temperature and washed with saturated aqNaCl, extracted with ethyl acetate (3 × 15 mL).The combined organic phase was dried with anhydrous Na 2 SO 4 , filtrated and concentrated under vacuum to yield the crude product.The crude product was purified by thin layer chromatography on silica gel with petroleum ether as eluent.

Conclusions
In summary, an efficient protocol for arylated pyridines from conjugated acetylenes and substituted benzylamines catalyzed by base was developed, which gives a much more convenient approach to obtain arylated pyridines with good to excellent yields.Compared to the approachreported by Chalk [21], the advantages of this protocol are inthe absence ofbyproduct detected by GC-MS even if the reaction was carried out in the air.Efforts to understand this reaction mechanism are in progress in our laboratory.
Supplementary Materials: Supplementary materials are available online.

Table 1 .
Optimization of the reaction conditions a .

Table 1 .
Optimization of the reaction conditions a .

Table 2 .
Synthesis of arylated pyridines from conjugated acetylenes and substituted benzylamines under optimized conditions.a

Table 2 .
Synthesis of arylated pyridines from conjugated acetylenes and substituted benzylamines under optimized conditions.a

Table 2 .
Synthesis of arylated pyridines from conjugated acetylenes and substituted benzylamines under optimized conditions.a

Table 2 .
Synthesis of arylated pyridines from conjugated acetylenes and substituted benzylamines under optimized conditions.a

Table 2 .
Synthesis of arylated pyridines from conjugated acetylenes and substituted benzylamines under optimized conditions.a

Table 2 .
Synthesis of arylated pyridines from conjugated acetylenes and substituted benzylamines under optimized conditions.a

Table 2 .
Synthesis of arylated pyridines from conjugated acetylenes and substituted benzylamines under optimized conditions.a

Table 2 .
Synthesis of arylated pyridines from conjugated acetylenes and substituted benzylamines under optimized conditions.a

Table 2 .
Synthesis of arylated pyridines from conjugated acetylenes and substituted benzylamines under optimized conditions.a

Table 2 .
Synthesis of arylated pyridines from conjugated acetylenes and substituted benzylamines under optimized conditions.a

Table 2 .
Synthesis of arylated pyridines from conjugated acetylenes and substituted benzylamines under optimized conditions.a

Table 2 .
Synthesis of arylated pyridines from conjugated acetylenes and substituted benzylamines under optimized conditions.a

Table 2 .
Synthesis of arylated pyridines from conjugated acetylenes and substituted benzylamines under optimized conditions.a