Two configurationally isomeric ligands, namely, 2-((E)benzylideneamino)-3-((pyridin-2-ylmethyl)amino)maleonitrile (HL 1 ) and 2-(benzylamino)-3-((E)-(pyridin-2-ylmethylene)amino)maleonitrile (HL 2 ), were synthesized and fully characterized, which are malenonitrile-tethered, N atom donors tridentate ligands. Structurally, they differ in the interchangeable position of amine and imine group only. Under the same reaction condition, Ni(II) invoked the transformation of (L 1 ) − to (L 2 ) − via simultaneous oxidation of amine to imine and the reduction of imine to amine. Two sequential 1,5-proton transfer pathways were anticipated for this type of unusual amine-imine oxidation/reduction process under acidic medium. In contrast, Co(II) was silent to such amine-imine interconversion reactions under both HL 1 and HL 2 ligand environment. The variation in electronic requirement might differentiate between both ligands such that HL 2 influenced the arial oxidation of Co(II) to Co(III) but HL 1 could not. The redox chemistry of Co(II)/Co(III) complexes with either HL 1 or HL 2 was explained using cyclic voltammetry and UV−vis spectroscopy.

Herein, we report two newly synthesized salen‐type ligands, 2,3‐bis((3,5‐di‐tert‐butyl‐2‐hydroxybenzyl)thio)maleonitrile (H2L1) and 2,3‐bis((3,5‐di‐tert‐butyl‐2‐hydroxybenzyl)amino)malenonitrile (H4L2), bearing different coordination sites (sulfur vs amine) at maleonitrile tethered moiety to investigate metal mediated non‐innocence chemistry of these ligands. Upon metallation, ligand H2L1 did not yield simple metal‐ligand complex, rather ligand was split into two organic fragments, dithiolene moiety (mnt)2− and phenol moiety via C−S bond cleavage wherein (mnt)2− formed a stable metal complex [M(mnt)2]2−. The C−S bond cleavage was interpreted in terms of strong p(π) … d(π) interaction between metal and dithiolene moiety in H2L1 ligand that invoked the intramolecular rearrangement facilitating C−S bond cleavage. Interestingly, the phenol moiety further transformed to either unprecedented 2,4‐di‐tert‐butyl‐6‐methylenecyclohexa‐2,4‐dienone (i. e. spiro compound; 5) or 2,4‐di‐tert‐butyl‐6‐(hydroxymethyl)phenol (6) depending on the temperature of reaction and type of metal ion used which was further predicted using DFT calculation. On the other hand, combined experimental and DFT studies explained that upon metallation, ligand H4L2 yielded non‐cleavage [M(H2L2)] (3 for M=Cu(II) and 4 for M=Ni(II) ) complex, which slowly oxidized at −NH−CH2‐(amine) region to −N=CH− (imine) in H2L2 ligand under aerobic environment via C−H bond activation, yielding [CuII(L3)] (1) (or [NiII(L3)] (2) complex (H2L3=oxidatively dehydrogenated product of H4L2 ligand.

Synthesizing hydrosulfido Cu thiolate complexes is quite challenging. In this report, two new and rare hydrosulfido Cu thiolate complexes, [Et4N]2[(mnt)­Cu-SH] (2, mnt = maleonitrile dithiolene = S2C2(CN)2) and [Et4N]3[(mnt)­Cu-(μ-SH)-Cu­(mnt)] (3), have been synthesized. Coordination sites and O2 activation by complex 2 resemble the formylglycine generating enzyme (FGE), an enzyme recently crystallographically characterized with sulfur-only coordination around Cu (three thiolate ligands). The function of this enzyme (and complex 2) is surprising because vulnerable thiolates should not be well suited for O2 activation rationally. Indeed, activation of oxygen by such an all-sulfur-coordinated Cu complex 2 is lacking in the literature. Aerial O2 (ambient O2 from the air) activation by complex 2 could proceed through a superoxide radical intermediate and a sulfur radical intermediate detected by resonance Raman (rR) spectroscopy and electron paramagnetic resonance (EPR) spectroscopy, respectively. The chemistry of 2 has been examined by its reactivity, crystal structure, and spectroscopic and cyclic voltammetric analyses. In addition, the results have been complemented with density functional theory (DFT) and time-dependent DFT (TD-DFT) calculations.

Nintedanib, a potent, oral, small‐molecule tyrosine kinase inhibitor, is known as a triple angiokinase inhibitor, inhibiting three major signaling pathways in angiogenesis. Here, we report full details of the alternative path toward the synthesis of nintedanib via novel intermediates. A key feature of our approach is the stereoselective intramolecular cyclization strategy that enables the concise conversion of β‐keto amide into a 3‐acyloxindole derivative, which is an important scaffold for nintedanib synthesis. Subsequent condensation of oxindole scaffold with synthesized amine derivative led to the drug nintedanib with good yields.