2-Amino-5-chloropyridine: An In-Depth Exploration

Introduction

2-Amino-5-chloropyridine is a chlorinated derivative of pyridine. It is widely utilized in various chemical synthesis processes, particularly in the pharmaceutical industry, where it serves as an essential intermediate in producing numerous drugs.

2-Amino-5-chloropyridine is an off-white to light yellow crystalline and exhibits moderate solubility in water, with greater solubility in organic solvents such as ethanol and methanol. The physical property of this compound is shown below[1].

Synthesis method

The electrochemical hydrogenation was carried out by dissolving 5-chloro-2-nitropyridine (5.0 g) in ethanol (50 mL) containing 10% sulphuric acid (15 mL) at a constant current density of 100 A/m2 in an undivided cell equipped with a nickel cathode (3×4 cm2 ) and a copper anode (3×4 cm2 ). These electrodes were connected to a DC power supply, and 2F of charge passed. The cell was then kept under an atmosphere of nitrogen, and the contents were stirred using a magnetic stirrer. At the end of the reaction, the electrolyte solution was diluted with water, the product was extracted into ether, washed with water, dried over anhydrous magnesium sulphate, and the evaporation of the solvent gave 4.1 g of 2-amino-5-chloropyridine in 82% isolated yield; mp 136–138°C[2].

Uses

The 2-amino-5-chloropyridine is a non-hygroscopic simple organic material, with a molecular formula of C5H5ClN2. It is expected to be a candidate for a low dielectric constant material.

In organic synthetic chemistry，2-amino-5-chloropyridine is a versatile building block that can create a range of compounds, such as 6-aminonicotinic acid. The six-electron reduction of a nitro group to the corresponding amine is well known, and the electrochemical conversion of 5-chloro-2-nitropyridine to 2-amino-5-chloropyridine at a nickel cathode and copper anode in the presence of acid proceeded in up to 84% yield. Reductive-carboxylation of this then gave 6-aminonicotinic acid in 78% yield.

Reference

[1] M. Pourayoubi, A. A. E. Valmoozi, S. Ghadimi. “A redetermination of 2-amino-5-chloropyridine at 100 K.” Acta crystallographica. Section E, Structure reports online 39 1 (2007).

[2] R. Ramesh Raju, S. Jayarama Reddy, S. Krishna Mohan. “Electroorganic synthesis of 6-aminonicotinic acid from 2-amino-5-chloropyridine.” Tetrahedron Letters 44 21 (2003): Pages 4133-4135.