Iodine-Mediated Heterocyclization for the Synthesis of 6-Alkylthio-1,3,5-triazine-2,4-diamines from N-Alkylpyridinium Salts and NH4SCN.

An iodine-mediated method for the synthesis of 6-alkylthio-1,3,5-triazine-2,4-diamines by the reaction of N-alkylpyridinium salts and NH4SCN in air is reported. Twenty-seven compounds were obtained under the standard conditions. Pyridinium salts work as benzyl-group transfer reagents to promote the formation of the CBn-SSCN bond and thereby the construction of the triazine skeleton. A plausible mechanism is proposed based on the experimental results and literature survey.

Chain Extension of Piperazine in Ethanol: Synthesis of 2-(4-(2-(Phenylthio)ethyl)piperazinyl)acetonitriles and ACAT-1 Inhibitors.

A base-induced synthesis of 2-(4-(2-(phenylthio)ethyl)piperazinyl) acetonitriles by reaction of disulfides, 1-(chloromethyl)-4-aza-1-azonia bicyclo[2.2.2]octane chloride and trimethylsilyl cyanide is reported. The scope of the method is demonstrated with 30 examples. The reaction mechanism research indicates that the three-component reaction would be a SN2 reaction. The products exhibit good activities towards advanced synthesis of aqueous soluble acyl-CoA: cholesterol O-acyltransferase-1 (ACAT-1) inhibitors. Our work is superior as it uses less-odor disulfides as carbon sources and EtOH as solvent in a water and dioxygen insensitive reaction system, followed by a simple purification process.

Copper-Catalyzed Oxidative [3 + 2] Cycloaddition of N-Alkyl Pyridinium Salts to Imidazo[1,2-a]pyridines.

A copper-catalyzed reaction of pyridinium salts and trimethylsilyl cyanide (TMSCN) in the presence of diethyl phosphite is developed. This reaction, which allows the single-step construction of biologically important 2-cyanoimidazo[1,2-a]pyridine from readily available starting materials, is realized for the first time and is feasible at the gram scale. The scope of the protocol is demonstrated with 27 examples. A consecutive double cyanation and cyclization can be achieved in this one-pot process. TMSCN plays a dual role not only as the "CN" source but also as the coupling partner for the cyclization of imidazo[1,2-a]pyridines.

Three-Component Cycloaddition of Nitriles: Construction of Bicyclic 4-Aminopyrimidines and Their Photophysical Studies.

A base-induced synthesis of bicyclic 4-aminopyrimidines by the cycloaddition of three types of nitriles is reported. The scope of the method is demonstrated with 44 examples. Products are found to have luminescence properties and show potential applications as organic luminescent layer materials.

Synthesis of methylene-bridged α,ß-unsaturated ketones: α-Csp3-H methylenation of aromatic ketones using Selectfluor as a mild oxidant.

A three starting material four component reaction (3SM-4CR) is developed for the synthesis of α,ß-unsaturated ketones and ß-amino ketones in good yields. The reaction employs tetramethylethylenediamine (TMEDA) as a methylene and terminal olefin source, and Selectfluor as a mild oxidant. TMEDA worked as a dual synthon to provide two carbons in this metal-free transformation process. The scope and versatility of the methods have been demonstrated with 23 examples. A Selectfluor-promoted oxidative reaction mechanism is proposed based on the results of the experimental studies.

Selectfluor facilitated bridging of indoles to bis(indolyl)methanes using methyl tert-butyl ether as a new methylene precursor.

A novel, green and efficient method is developed for the synthesis of methylene bridged bis(indolyl)methanes in good to excellent yields. The reaction employs methyl tert-butyl ether (MTBE) as the methylene source and selectfluor as an oxidizing agent. The scope and versatility of the methods have been successfully demonstrated with 48 examples. The metal-free transformation process is suitable for scale-up production. A selectfluor-promoted oxidative reaction mechanism is proposed based on the results of the experimental studies.

A three-component iodine-catalyzed oxidative coupling reaction: a heterodifunctionalization of 3-methylindoles.

A metal-free method for the synthesis of heterodifunctional indole derivatives is developed through TBHP/KI-mediated oxidative coupling. The reaction constructs C-O and C-C bonds in succession with the help of tert-butyl peroxy radicals generated by the TBHP/KI catalytic system, enabling the direct realization of the heterodifunctionalization of indole in one pot. The product of this reaction is a novel heterodifunctional compound. This work might provide a new effective method for the synthesis of polycyclic indole compounds.

Experimental and mechanistic insights into copper(ii)-dioxygen catalyzed oxidative N-dealkylation of N-(2-pyridylmethyl)phenylamine and its derivatives.

A di-(2-pyridylmethyl)phenylamine ((PyCH2)2NPh) supported Cu(ii)/O2 catalytic system was explored with the synthesis of pyridylmethyl-based compounds of carboxylate (PyCOOH), amide (PyC(O)NHPh), and imine (PyCH[double bond, length as m-dash]NPh) from the oxidative N-dealkylation of N-(2-pyridylmethyl)phenylamine (PyCH2NHPh) and its derivatives, by means of controlling the addition of a base and/or water to the reaction system under a dioxygen atmosphere at room temperature. Experimental studies showed that the imine and amide species could be precursors in succession in the way to the final oxidation state of carboxylates. A cyclic catalytic mechanism was proposed including the base triggered C-H bond activation of the 2-pyridylmethyl group (PyCH2-) and the intermolecular Cu-OOH α-hydrogen atom abstraction from the coordinated imine substrate (PyCH[double bond, length as m-dash]NPh).

Kinetics and mechanistic analysis of an extremely rapid carbon dioxide fixation reaction.

Carbon dioxide may react with free or metal-bound hydroxide to afford products containing bicarbonate or carbonate, often captured as ligands bridging two or three metal sites. We report the kinetics and probable mechanism of an extremely rapid fixation reaction mediated by a planar nickel complex [Ni(II)(NNN)(OH)](1-) containing a tridentate 2,6-pyridinedicarboxamidate pincer ligand and a terminal hydroxide ligand. The minimal generalized reaction is M-OH + CO(2) → M-OCO(2)H; with variant M, previous rate constants are ≲10(3) M(-1) s(-1) in aqueous solution. For the present bimolecular reaction, the (extrapolated) rate constant is 9.5 × 10(5) M(-1) s(-1) in N,N'-dimethylformamide at 298 K, a value within the range of k(cat)/K(M)≈10(5)-10(8) M(-1) s(-1) for carbonic anhydrase, the most efficient catalyst of CO(2) fixation reactions. The enthalpy profile of the fixation reaction was calculated by density functional theory. The initial event is the formation of a weak precursor complex between the Ni-OH group and CO(2), followed by insertion of a CO(2) oxygen atom into the Ni-OH bond to generate a four center Ni(η(2)-OCO(2)H) transition state similar to that at the zinc site in carbonic anhydrase. Thereafter, the Ni-OH bond detaches to afford the Ni(η(1)-OCO(2)H) fragment, after which the molecule passes through a second, lower energy transition state as the bicarbonate ligand rearranges to a conformation very similar to that in the crystalline product. Theoretical values of metric parameters and activation enthalpy are in good agreement with experimental values [ΔH(‡) = 3.2(5) kcal/mol].

Direct transformation of nitriles to cyanide using chloride anion as catalyst.

A simple method is explored for the scission of C-CN bonds into aldehyde and CN- in air. The transformation was mediated by chloride anions. The cyanide anions were extracted from the reaction solution to form (Et4N)2[Zn(CN)4] and (Et4N)2[Ni(CN)4]. A chloride-induced reaction mechanism is proposed based on experimental studies and DFT calculations. This work might guide the study of halogen catalysts for C-C bond cleavage.

Synthesis of N,O-bidentate organic difluoroboron complexes and their photophysical studies.

We disclose a novel boron trifluoride induced C-H activation and difluoroboronation at room temperature, thus providing a straightforward gateway to a series of N,O-bidentate organic BF2 complexes. The scope of the method is demonstrated with 24 examples. All the synthesized compounds exhibit fluorescence and some of them have large Stokes shifts.

π-Extension of Indoles Using Acrolein Linker: Synthesis of Indolo[3,2-a]carbazole-6-carbaldehydes and Racemosin B.

A simple method for the synthesis of indolo[3,2-a]carbazole-6-carbaldehydes by the π-extension of indoles with acrolein is reported. The scope of the method is demonstrated with 33 examples. The products exhibit high activities toward advanced synthesis and are proved to be able to produce valuable chemicals, such as natural products, dyes, and organic fluorescent materials. In addition, the alkaloid racemosin B can be prepared by this method in two steps in ∼50% overall yield.

Synthesis of binucleating macrocycles and their nickel(II) hydroxo- and cyano-bridged complexes with divalent ions: anatomical variation of ligand features.

The planar NNN-pincer complexes [M(II)(pyN(2)(Me2))(OH)](1-) (M(II) = Ni, Cu) fix CO(2) in η(1)-OCO(2)H complexes; results for the copper system are described. Mn(II), Fe(II), Co(II), and Zn(II) behave differently, forming [M(II)(pyN(2)(Me2))(2)](2-) with N(4)O(2) coordination. Incorporation of the Ni(II) pincer into binucleating macrocycle 2 containing a triamino M(II) locus connected by two 1,3-biphenylene groups affords proximal Ni(II) and M(II) sites for investigation of the synthesis, structure, and reactivity of Ni-X-M bridge units. This ligand structure is taken as a reference for variations in M(II) atoms and binding sites and bridges X = OH(-) and CN(-) to produce additional members of the macrocyclic family with improved properties. Macrocycle 2 with a 22-membered ring is shown to bind M(II) = Mn, Fe, and Cu with hydroxo bridges. Introduction of the 4-Bu(i)O group (macrocycle 3) improves the solubility of neutral complexes such as those with Ni(II)-OH-Cu(II) and Ni(II)-CN-Fe(II) bridges. Syntheses of macrocycle 5 with a 7-Me-[12]aneSN(3) and macrocycle 6 with a 1,8-Me(2)-[14]aneN(4) M(II) binding site are described together with hydoxo-bridged Ni/Cu and cyano-bridged Ni/Fe complexes. This work was motivated by the presence of a Ni···(HO)-Fe bridge grouping in a reactive state of carbon monoxide dehydrogenase. Attempted decrease in Ni-(OH)-M distances (3.70-3.87 Å) to smaller values observed in the enzyme by use of macrocycle 4 having 1,2-biphenylene connectors led to a mononuclear octahedral Ni(II) complex. Bridge structural units are summarized, and the structures of 14 macrocyclic complexes including 8 with bridges are described.

Solvent-Free Strategy for Direct Access to Versatile Quaternary Ammonium Salts with Complete Atom Economy.

A solvent-free method for the synthesis of quaternary ammonium salts (QAS) by iodoquaternization of alkenes with N-heteroarenes was reported. Its advantages lie in energy-saving and clean production by using iodine as the oxidant and manual grinding the starting materials, together with the complete atom economy and low process mass intensity (PMI) value. Demonstrated by 50 examples, the generated QAS was proved to be able to produce valuable chemicals, such as biological protease inhibitors, anti-cancer agents, and organic fluorescent materials.

Copper(II)-Catalyzed Selective CAr-H Bond Formylation: Synthesis of Dialdehyde Aniline.

A simple and efficient method for the synthesis of dialdehyde aniline in good yields (up to 83%) is explored using Cu(OTf)2 as the catalyst, Selectfluor as the radical initiator, and DMSO as both the carbon and oxygen sources. Experimental studies indicate that the reaction is achieved by the formylation of two CAr-H bonds, first at the para-position and then at the ortho-position. A possible mechanism is proposed, including the thermal homolysis of Selectfluor, the Cu(II)-facilitated formylation of the CAr-H bonds, and the hydrolysis of the amide under alkaline conditions in air atmosphere.

Iodine-Mediated Pyridine Ring Expansion for the Construction of Azepines.

A synthesis of azepines by the expansion of pyridine rings promoted by iodine in air is reported. The scope of the method is demonstrated with 27 examples. Two iodinations are involved in the reaction, in which the second iodination leads to the opening of the six-membered ring.

Redox non-innocence of thioether crowns: spectroelectrochemistry and electronic structure of formal nickel(III) complexes of aza-thioether macrocycles.

The Ni(II) complexes [Ni([9]aneNS(2)-CH(3))(2)](2+) ([9]aneNS(2)-CH(3)=N-methyl-1-aza-4,7-dithiacyclononane), [Ni(bis[9]aneNS(2)-C(2)H(4))](2+) (bis[9]aneNS(2)-C(2)H(4)=1,2-bis-(1-aza-4,7-dithiacyclononylethane) and [Ni([9]aneS(3))(2)](2+) ([9]aneS(3)=1,4,7-trithiacyclononane) have been prepared and can be electrochemically and chemically oxidized to give the formal Ni(III) products, which have been characterized by X-ray crystallography, UV/Vis and multi-frequency EPR spectroscopy. The single-crystal X-ray structure of [Ni(III)([9]aneNS(2)-CH(3))(2)](ClO(4))(6)·(H(5)O(2))(3) reveals an octahedral co-ordination at the Ni centre, while the crystal structure of [Ni(III)(bis[9]aneNS(2)-C(2)H(4))](ClO(4))(6)·(H(3)O)(3)·3H(2)O exhibits a more distorted co-ordination. In the homoleptic analogue, [Ni(III)([9]aneS(3))(2)](ClO(4))(3), structurally characterized at 30 K, the Ni-S distances [2.249(6), 2.251(5) and 2.437(2) Å] are consistent with a Jahn-Teller distorted octahedral stereochemistry. [Ni([9]aneNS(2)-CH(3))(2)](PF(6))(2) shows a one-electron oxidation process in MeCN (0.2 M NBu(4)PF(6), 293 K) at E(½)=+1.10 V versus Fc(+)/Fc assigned to a formal Ni(III)/Ni(II) couple. [Ni(bis[9]aneNS(2)-C(2)H(4))](PF(6))(2) exhibits a one-electron oxidation process at E(½)=+0.98 V and a reduction process at E(½)=-1.25 V assigned to Ni(II)/Ni(III) and Ni(II)/Ni(I) couples, respectively. The multi-frequency X-, L-, S-, K-band EPR spectra of the 3+ cations and their 86.2% (61)Ni-enriched analogues were simulated. Treatment of the spin Hamiltonian parameters by perturbation theory reveals that the SOMO has 50.6%, 42.8% and 37.2% Ni character in [Ni([9]aneNS(2)-CH(3))(2)](3+), [Ni(bis[9]aneNS(2)-C(2)H(4))](3+) and [Ni([9]aneS(3))(2)](3+), respectively, consistent with DFT calculations, and reflecting delocalisation of charge onto the S-thioether centres. EPR spectra for [(61)Ni([9]aneS(3))(2)](3+) are consistent with a dynamic Jahn-Teller distortion in this compound.

Fast carbon dioxide fixation by 2,6-pyridinedicarboxamidato-nickel(II)-hydroxide complexes: influence of changes in reactive site environment on reaction rates.

The planar complexes [Ni(II)(pyN(2)(R2))(OH)](-), containing a terminal hydroxo group, are readily prepared from N,N'-(2,6-C(6)H(3)R(2))-2,6-pyridinedicarboxamidate(2-) tridentate pincer ligands (R(4)N)(OH), and Ni(OTf)(2). These complexes react cleanly and completely with carbon dioxide in DMF solution in a process of CO(2) fixation with formation of the bicarbonate product complexes [Ni(II)(pyN(2)(R2))(HCO(3))](-) having η(1)-OCO(2)H ligation. Fixation reactions follow second-order kinetics (rate = k(2)'[Ni(II)-OH][CO(2)]) with negative activation entropies (-17 to -28 eu). Reactions were monitored by growth and decay of metal-to-ligand charge-transfer (MLCT) bands at 350-450 nm. The rate order R = Me > macro > Et > Pr(i) > Bu(i) > Ph at 298 K (macro = macrocylic pincer ligand) reflects increasing steric hindrance at the reactive site. The inherent highly reactive nature of these complexes follows from k(2)' ≈ 10(6) M(-1) s(-1) for the R = Me system that is attenuated by only 100-fold in the R = Ph complex. A reaction mechanism is proposed based on computation of the enthalpic reaction profile for the R = Pr(i) system by DFT methods. The R = Et, Pr(i), and Bu(i) systems display biphasic kinetics in which the initial fast process is followed by a slower first order process currently of uncertain origin.

Reactions of the terminal Ni(II)-OH group in substitution and electrophilic reactions with carbon dioxide and other substrates: structural definition of binding modes in an intramolecular Ni(II)...Fe(II) bridged site.

A singular feature of the catalytic C-cluster of carbon monoxide dehydrogenase is a sulfide-bridged Ni...Fe locus where substrate is bound and transformed in the reversible reaction CO + H(2)O right harpoon over left harpoon CO(2) + 2H(+) + 2e(-). A similar structure has been sought in this work. Mononuclear planar Ni(II) complexes [Ni(pyN(2)(Me2))L](1-) (pyN(2)(Me2) = bis(2,6-dimethylphenyl)-2,6-pyridinedicarboxamidate(2-)) derived from a NNN pincer ligand have been prepared including L = OH(-) (1) and CN(-) (7). Complex 1 reacts with ethyl formate and CO(2) to form unidentate L = HCO(2)(-) (5) and HCO(3)(-) (6) products. A binucleating macrocycle was prepared which specifically binds Ni(II) at a NNN pincer site and five-coordinate Fe(II) at a triamine site. The Ni(II) macrocyle forms hydroxo (14) and cyanide complexes (15) analogous to 1 and 7. Reaction of 14 with FeCl(2) alone and with ethyl formate and 15 with FeCl(2) affords molecules with the Ni(II)-L-Fe(II) bridge unit in which L = mu(2):eta(1)-OH(-) (17) and mu(2):eta(2)-HCO(2)(-) (18) and -CN(-) (19). All bridges are nonlinear (17, 140.0 degrees ; 18, M-O-C 135.9 degrees (Ni), 120.2 degrees (Fe); 19, Ni-C-N 170.3 degrees , Fe-N-C 141.8 degrees ) with Ni...Fe separations of 3.7-4.8 A. The Ni(II)Fe(II) complexes, lacking appropriate Ni-Fe-S cluster structures, are not site analogues, but their synthesis and reactivity provide the first demonstration that molecular Ni(II)...Fe(II) sites and bridges can be attained, a necessity in the biomimetic chemistry of C-clusters.

Copper(II)-hydroxide facilitated C-C bond formation: the carboxamido pyridine system versus the methylimino pyridine system.

A copper(ii)-hydroxide-induced carbon-carbon bond formation reaction is explored with the synthesis of an asymmetric carboxamido-methylimino pyridine Cu(i) complex of [CuI(py(N-C[double bond, length as m-dash]O)(N[double bond, length as m-dash]C-C)ph2Me2)2]- (12). Two imine-methyl groups are coupled to form a bridged C-C bond (N[double bond, length as m-dash]C-C-C-C[double bond, length as m-dash]N) at the methyl positions with the reduction of two Cu2+ center ions to Cu+. The reaction is checked with three dicarboxamido pyridine [CuII-OH] complexes, with which dinuclear Cu(i) complexes of [Cu2(py(N-C[double bond, length as m-dash]O)2ph2R2)2]2- (R = methyl (3), methyl and allyl (6)) and trinuclear [CuII-CuI-CuII] complex of [Cu3(⊂20-py(N-C[double bond, length as m-dash]O)2ph2dienMe3)2]+ (9) are obtained. The reactivities of the [CuII-L] (L = DMF, OH-) complexes in dicarboxamido pyridine, carboxamido-methylimino pyridine and dimethylimino pyridine systems are discussed in terms of the electron delocalization properties of ligands. A cooperative metal-ligand (Cu2+ and enamide ligand) interaction is proposed based on the characterization of ligated Cu(ii) intermediates with the techniques of X-ray crystallography, UV-vis spectroscopy, cyclic voltammogram, EPR spectroscopy, and DFT calculations.