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. 2019 Jul 17;24(14):2609.
doi: 10.3390/molecules24142609.

Role of Pyridine Nitrogen in Palladium-Catalyzed Imine Hydrolysis: A Case Study of (E)-1-(3-bromothiophen-2-yl)-N-(4-methylpyridin-2-yl)methanimine

Gulraiz Ahmad  1 , Nasir Rasool  2 , Komal Rizwan  1   3 , Ataf Ali Altaf  4 , Umer Rashid  5 , Tariq Mahmood  6 , Khurshid Ayub  6
Affiliations

Role of Pyridine Nitrogen in Palladium-Catalyzed Imine Hydrolysis: A Case Study of (E)-1-(3-bromothiophen-2-yl)-N-(4-methylpyridin-2-yl)methanimine

Gulraiz Ahmad et al. Molecules. .

Abstract

In the present study, 4-methylpyridin-2-amine was reacted with 3-bromothiophene-2-carbaldehyde and the Schiff base (E)-1-(3-bromothiophen-2-yl)-N-(4-methylpyridin-2-yl)methanimine was obtained in a 79% yield. Coupling of the Schiff base with aryl/het-aryl boronic acids under Suzuki coupling reaction conditions, using Pd(PPh3)4 as catalyst, yielded products with the hydrolysis of the imine linkages (5a-5k, 6a-6h) in good to moderate yields. To gain mechanistic insight into the transition metal-catalyzed hydrolysis of the compounds, density functional theory (DFT) calculations were performed. The theoretical calculations strongly supported the experiment and provided an insight into the transition metal-catalyzed hydrolysis of imines.

Keywords: Thiophene; carbaldehyde; cleavage; hydrolysis; imine.; palladium.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Scheme 1
Scheme 1
Synthesis and Suzuki coupling of (E)-N-((3-bromothiophen-2-yl)methylene)-4-methylpyridin-2-amine Schiff base (3a) with arylboronic acids.
Scheme 2
Scheme 2
Previous report of Suzuki coupling of a Schiff base by our group [22].
Scheme 3
Scheme 3
Synthesis and Suzuki coupling of (E)-N-((5-bromothiophen-2-yl)methylene)-4-methylpyridin-2-amine (3b) with aryl/het-aryl boronic acids.
Scheme 4
Scheme 4
Synthesis and Suzuki coupling of (E)-N-((3-bromothiophen-2-yl)methylene)-6-methylpyridin-2-amine (3c) with aryl/het-aryl boronic acid.
Scheme 5
Scheme 5
Plausible mechanism for the imine hydrolysis. The association of the Suzuki coupling product with the Pd-catalyst is due to the presence of the pyridine ring, this attachment increases the polarity of the C=N linkage of the Schiff base and ultimately leads to hydrolysis products. The absence of the pyridine ring does not allow such attachment.
Figure 1
Figure 1
Hydrolysis pathway without the involvement of Palladium as a catalyst.
Figure 2
Figure 2
Hydrolysis pathway in the presence of palladium but without involvement of pyridine.
Figure 3
Figure 3
Hydrolysis pathway with palladium along with involvement of a pyridine moiety.
See this image and copyright information in PMC

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