Pyridazines

Introduction

Pyridazine, also called 1,2-diazine, is a class of hetero-aromatic organic compound with empirical formula C4H4N2. The chemical structure is a six-membered ring with two adjacent nitrogen atoms (Fig.1). Pyridazine is a privileged structure in medicinal chemistry and can be used as an isosteric replacement of phenyl or heteroaromatic rings. Pyridazines can improve the physiochemical properties of drug molecules by increasing their water solubility, participating as hydrogen bond acceptors, and have a high capacity to complex with targets due to their dipole moment. Pyridazine confers bioavailability, especially to the CNS, and can reduce toxicity. Pyridazine is a part of several drug molecules, and the pyradzine pharmacophore has led to a variety of pharmacologically active compounds. 

Pyridazines Fig. 1 The Skeletal formula with numbers, Ball-and-stick model and Space-filling model of pyridazine (cited from Wikipedia)

Application

Material Chemistry:

Haroutounian group have synthesized that 4’-hydroxystryrylpyridazines and studied their photophysical properties. The UV spectra of target molecules in ethanol show under neutral conditions a long wavelength absorbance at 330-350 nm, which shifts sharply to the red in both acid and base (388-424 nm). The absorbance and fluorescence of these compounds demonstrate strong dependence on solvent polarity and pH, making them as potential probes for biological systems. Polarity, pH and ion-sensing fluorescent probes based on quadrupolar substituted 1,4-distyrylbenzenes with a pyridazine central core has been investigated by Schmitt group (Fig. 2). The compounds 3 and 4 have been obtained by aldol condensation. Whereas variations of the environment only slightly alter the electronic excitation spectra, the fluorescence spectra appear to be highly responsible: a positive solvatochromism is observed and the compounds are very sensitive toward protonation and highly responsible to iron (III) ions.

PyridazinesFig.2 The structures of quadrupolar substituted 1,4-distyrylbenzenes with pyridazine

The two photon absorption (TPA) opens the way for both improved and novel technological capabilities such as multiphoton microscopy, microfabrication three-dimensional data-storage, optical power limiting and photodynamic therapy. A lot of pyrimidine derivatives have been described with interesting TPA properties. A series of conjugated compounds with a pyridazinium iodide moiety 104-107 have been synthesized by condensation of 4-methylpyridazinium iodide salt with various p-dialkylaminobenzaldehydes and characterized by Cheng et al[1]. (Fig.3). Strong second harmonic generation was obtained as well as Langmuir-Blodgett film forming properties. Among the factors which affect the second harmonic generation in the pyridazinium system, the high electron density around the second nitrogen in the pyridazine ring has been highlighted by the authors.

Pyridazines Fig.3 The pyrimidine derivatives with non linear optical property

The first example of the use of pyridazine as building block for the synthesis of thin film field-effect transistor has been described by Yasuda group. They described a series of π-conjugated (ABA)n-type polymers constructed of electron-donating thiophene or 3-alkylthiophene (as the unit A) and electron accepting pyridazine (as the unit B) obtained by palladium-catalyzed homocoupling reaction. The polymers served as good materials for thin film field-effect transistor and gave a hole mobility of 3 × 10−3 cm2·V−1·s−1.

Organic Synthesis:

A proper molecular structure is required for molecules to be liquid crystals: a rigid aromatic core, strong dipoles and/or easily polarisable substituents and generally long flexible arms. Synthesis of linear conjugated oligomers with ethynylpyridazine units using Sonogashira and Suzuki crosscoupling reactions has been described. The derivatives present interesting fluorescent and/or liquid crystal properties with smectic phases.

References

  1. The investigation of second harmonic generation from novel molecules [(E)-N-alkyl-4-{2-[4-(dialkylamino)phenyl]ethenyl}pyridazinium iodide. J. Mater. Chem., 1998,8, 931-935
  2. New liquid-crystalline compounds with negative dielectric anisotropy, Liq. Cryst., 1989, 5, 159-170
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