Guanabenz, a marketed antihypertensive drug, is primarily sold in its monoprotonated form, while its free base form has received little attention. Interestingly, under physiological conditions of temperature and pH, approximately 16% of guanabenz exists in its free base form. Our group recently discovered that the free base form of guanabenz is a tautomeric form of guanylhydrazones, known as azines.1 Notably, guanabenz prominently adopts the azine tautomeric state, as confirmed through both experimental and theoretical studies. This discovery has sparked a new research direction in our lab, focusing on this previously overlooked class of molecules: 1,1-diaminoazines. The unique characteristics of 1,1-diaminoazines directed us to employ them in different research areas of chemistry. 1,1-Diaminoazines are known to have applications in medicinal chemistry, material chemistry, catalysis, organic synthesis, etc.2 The presence of electrophilic and nucleophilic sites in the same molecule makes 1,1-diaminoazines a unique substrate (I) for cycloaddition reactions synthesising dihydropyrazoles and different types of substituted triazoles.3 The presence of a) the conjugated double bonds, (b) the many active hydrogen atoms, (c) the N2 centre in 1,1-diaminoazines acting as a proton acceptor, and (d) the iminic C4 acting as a hydrogen bond donor makes this molecule a potential bifunctional organocatalyst.4 To prove the same, this molecule has been used to catalyse various types of Michael addition reactions.5,6 Successfully, it has been utilised in C-P and C-C bond formation. Furthermore, it has facilitated the aldol/cyclisation cascade reactions, efficiently generating small heterocycles.7 Additionally, it has been proven efficient in carrying out different multi-component reactions (MCRs) to generate bioactive scaffolds such as pyranopyrazoles. Quantum chemical studies have been carried out to prove the mechanistic insights and to further enhance its utility, and efforts are currently underway to develop an asymmetric version of this catalyst. This modification aims to unlock its potential for enantioselective transformations, paving the way for the synthesis of complex molecules and expanding its applicability in medicinal chemistry. Other than this, 4-pyridyl-4 methyl-1,1-diaminoazine was employed to generate the pincer complex with Pd(OAc)2. The application of the complex in catalysing the medicinally important scaffold (e.g., benzimidazoles, quinolines, quinoxazolinones) synthesis using the ADC mechanism has been reported.8
[1] Cryst. Growth Des. 2019, 19, 3183 [2] Org. Biomol. Chem. 2019, 17, 8486. [3] J. Org. Chem. 2021, 86, 7659 [4] Chem. Comm. 2021, 57, 11717 [5] New J. Chem., 2023, 47, 1998 [6] Tetrahedron Lett., 2023, 122, 154505 [7] ChemistrySelect., 2024, 9, e202405002 [8] Org. Biomol. Chem., 2025, 23, 343
