Amidoximes Provide Facile Platinum(II)-Mediated Oxime–Nitrile Coupling

Abstract

The nucleophilic addition of amidoximes R'C(NH(2))═NOH [R' = Me (2.Me), Ph (2.Ph)] to coordinated nitriles in the platinum(II) complexes trans-[PtCl(2)(RCN)(2)] [R = Et (1t.Et), Ph (1t.Ph), NMe(2) (1t.NMe(2))] and cis-[PtCl(2)(RCN)(2)] [R = Et (1c.Et), Ph (1c.Ph), NMe(2) (1c.NMe(2))] proceeds in a 1:1 molar ratio and leads to the monoaddition products trans-[PtCl(RCN){HN═C(R)ONC(R')NH(2)}]Cl [R = NMe(2); R' = Me ([3a]Cl), Ph ([3b]Cl)], cis-[PtCl(2){HN═C(R)ONC(R')NH(2)}] [R = NMe(2); R' = Me (4a), Ph (4b)], and trans/cis-[PtCl(2)(RCN){HN═C(R)ONC(R')NH(2)}] [R = Et; R' = Me (5a, 6a), Ph (5b, 6b); R = Ph; R' = Me (5c, 6c), Ph (5d, 6d), correspondingly]. If the nucleophilic addition proceeds in a 2:1 molar ratio, the reaction gives the bisaddition species trans/cis-[Pt{HN═C(R)ONC(R')NH(2)}(2)]Cl(2) [R = NMe(2); R' = Me ([7a]Cl(2), [8a]Cl(2)), Ph ([7b]Cl(2), [8b]Cl(2))] and trans/cis-[PtCl(2){HN═C(R)ONC(R')NH(2)}(2)] [R = Et; R' = Me (10a), Ph (9b, 10b); R = Ph; R' = Me (9c, 10c), Ph (9d, 10d), respectively]. The reaction of 1 equiv of the corresponding amidoxime and each of [3a]Cl, [3b]Cl, 5b-5d, and 6a-6d leads to [7a]Cl(2), [7b]Cl(2), 9b-9d, and 10a-10d. Open-chain bisaddition species 9b-9d and 10a-10d were transformed to corresponding chelated bisaddition complexes [7d](2+)-[7f](2+) and [8c](2+)-[8f](2+) by the addition of 2 equiv AgNO(3). All of the complexes synthesized bear nitrogen-bound O-iminoacylated amidoxime groups. The obtained complexes were characterized by elemental analyses, high-resolution ESI-MS, IR, and (1)H NMR techniques, while 4a, 4b, 5b, 6d, [7b](Cl)(2), [7d](SO(3)CF(3))(2), [8b](Cl)(2), [8f](NO(3))(2), 9b, and 10b were also characterized by single-crystal X-ray diffraction.

Highly Reactive NiII‐Bound Nitrile–Oxime Coupling Intermediates Stabilized by Substituting Conventional Nitriles with a Dialkylcyanamide

“…Nickel(II) belongs to the category of labile metal centers with flexible coordination geometry, and formation of the Ni II complexes of different composition can be explained in terms of lower solubility of the released nickel species and/or packing effects. Although we did not detect any intermediates (for instance, intermediates derived from the addition of one oxime to one cyanamide ligand), it is believed that the addition proceeds sequentially, as in the previously reported platinum(II)‐mediated oxime–nitrile couplings 15. Similar adducts had previously been described only for Ni II ‐mediated reactions between functionalized oximes and conventional nitriles, which led to the formation of stable polydentate iminoligands 16.…”

“…Despite the wealth of chemistry associated with the nucleophilic addition of the oxime HON=C functionality to the so‐called conventional nitrile NCR (R = alkyl, aryl) ligands, only a few works14,17 have explored metal‐bound dialkylcyanamides – NCNAlk 2 – as substrates for the addition. These reports indicate substantial distinctions in the reaction rates and the nature of products formed, [2e,3a,3b,14,17e–17g,18] and it means that these variances were recognized not only at the quantitative,3b,17f but also at the qualitative level when dialkylcyanamides and conventional nitrile ligands react with the same reagent in absolutely different ways giving, consequently, different products. [3a,3b,17f,17g,18]…”

“…It was recognized earlier that in many instances ligated Alk 2 NCN compounds exhibit different behavior from the coordinated conventional nitriles RCN. These differences were recognized not only at the quantitative,17f,30 but also at the qualitative level2e,3a,3b,3e when conventional nitrile and dialkylcyanamide ligands react with the same reagent in different ways to give, consequently, different products. The distinctions in the reaction routes are accounted for by a special role of the NR 2 group in dialkylcyanamides.…”

A Dimetallic Aminonitrone Nickel(II) Complex: Further Insights into Metal‐Mediated Nucleophilic Activation of Amidoximes

“…A similar reaction of acetamidoxime with aliphatic nitriles, viz. MeCN, EtCN, and PhCH 2 CN, did not give the analogous dimetallic complexes under these reaction conditions and led to a broad mixture of unidentified species along with the starting acetamidoxime and nitrile even after reaction for 3 d. Lower reactivity of the aliphatic nitrile species and corresponding aliphatic O ‐iminoacyl amidoximes have been previously observed ,…”

Elemental bioimaging of platinum in mouse tissues by laser ablation-inductively coupled plasma-mass spectrometry for the study of localization behavior of structurally similar complexes

“…Similar structures have been found as precursors for different metal complexes (Pt, Zn, Ni, Pd, Co). These precursors can further be used to synthesize the amidoximes, which are attractive blocks for the medicinal chemists [36]. Because the structure of complexes containing cyanamides differs so radically from that of complexes containing aromatic ligands, the resultant difference in lipophilicity or solubility will affect the cellular uptake of the complexes, hence also influencing their pharmacokinetic behaviors regarding bioavailability, efficacy and toxicity.…”