Reductive activation of arenes

Stable cyanomethylcyclohexadienyl anions generated in two-electron reduction of isomeric tolunitriles by potassium in liquid ammonia were detected by NMR spectroscopy. The chemical shifts in these anions were obtained from density functional (PBE/3z) quantum chemical calculations and the electron density distributions for the anions were calculated in the framework of the NBO approach at the HF/6-31+G* level of theory. The experimental and calculated δ_C values are in good agreement. Changes in the δ_C values on going from the starting nitriles to the corresponding anions are linearly related to the calculated π-electron densities on the pentadienyl ring carbon atoms. Dedicated to the memory of Academician V. A. Koptyug on the occasion of the 75th anniversary of his birth. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 6, pp. 940–944, June, 2006.     

Reductive activation of arenes

Reductive alkylation of benzonitrile, ortho-, meta-, para-tolunitriles, and 1-naphthonitrile by sequential action of alkali metal and alkyl bromide in liquid ammonia results in corresponding alkylarenes and 1-alkyl-1-cyanocyclohexa-2,5-dienes. The experimental conditions for target synthesis of the specified products are found. A method of synthesis of 1-(ω-bromoalkyl)-1-cyanocyclohexa-2,5-dienes based on the interaction of two-electronic reduction products of aromatic nitriles with α,ω-dibromoalkanes Br(CH₂)_nBr (_n = 3−5) is developed.     

Reductive activation of nitrate reductases

Protein film voltammetry of Paracoccus pantotrophus respiratory nitrate reductase (NarGH) and Synechococcus elongatus assimilatory nitrate reductase (NarB) shows that reductive activation of these enzymes may be required before steady state catalysis is observed. For NarGH complementary spectroscopic studies suggest a structural context for the activation. Catalytic protein film voltammetry at a range of temperatures has allowed quantitation of the activation energies for nitrate reduction. For NarGH with an operating potential of ca. 0.05 V the activation energy of ca. 35 kJ mol-1 is over twice that measured for NarB whose operating potential is ca. -0.35 V.     

Reductive activation of dioxygen by a myoglobin reconstituted with a flavohemin

We successfully converted myoglobin, an oxygen-storage hemoprotein, into an oxygen-activating hemoprotein like cytochrome P450s by replacing the native hemin with the artificially created flavohemin. The reconstituted myoglobin, rMb(1), was chacterized by ESI-TOF-mass, UV-vis, and fluorescence spectra. The 1H NMR spectrum of cyanomet rMb(1) indicates that two hemin conformers are present in a ratio of 1:1. Upon the addition of NADH to the buffer solution of rMb(1) in the presence of SOD and catalase, the oxymyoglobin was rapidly formed. As compared with the formation of the oxygenated native myoglobin in the presence of 10-N-(acetylaminoethyl)isoalloxazine, the rate constant of the oxyheme formation in rMb(1) is 6 times larger. This is because the flavin covalently linked to the terminal heme propionate functions as an effective mediator of an electron transfer from NADH to the hemin in rMb(1). Furthermore, rMb(1) shows the deformylation activity, when 2-phenylpropionaldehyde (2-PPA) was employed as a substrate. This result indicates that the oxyheme is reductively activated to Fe(III)-peroxoanion (Fe(III)-O22-). The result in this report is the first example of the activation of dioxygen by myoglobin. This study shows the utility of the replacement of the native hemin with a chemically modified one for the functionalization of myoglobin.     

Copper-mediated C-H activation/C-S cross-coupling of heterocycles with thiols

We report the synthesis of a series of aryl- or alkyl-substituted 2-mercaptobenzothiazoles by direct thiolation of benzothiazoles with aryl or alkyl thiols via copper-mediated aerobic C-H bond activation in the presence of stoichiometric CuI, 2,2'-bipyridine and Na(2)CO(3). We also show that the approach can be extended to thiazole, benzimidazole, and indole substrates. In addition, we present detailed mechanistic investigations on the Cu(I)-mediated direct thiolation reactions. Both computational studies and experimental results reveal that the copper-thiolate complex [(L)Cu(SR)] (L: nitrogen-based bidentate ligand such as 2,2'-bipyridine; R: aryl or alkyl group) is the first reactive intermediate responsible for the observed organic transformation. Furthermore, our computational studies suggest a stepwise reaction mechanism based on a hydrogen atom abstraction pathway, which is more energetically feasible than many other possible pathways including β-hydride elimination, single electron transfer, hydrogen atom transfer, oxidative addition/reductive elimination, and σ-bond metathesis.     

Transition metal-free activation of allylic acetates toward regioselective S-allylation of thiols

Allylic acetates have been used as allylating agents under transition metal-free condition toward an economical and sustainable regioselective S-allylation of aromatic and aliphatic thiols in the presence of potassium carbonate in DMF.     

Reductive displacement of allylic acetates by hydride transfer via catalytic activation by palladium(0) complexes

Allylic acetates are reduced to alkenes by reductive displacement by hydride reagents via catalytic activation with Pd(0) complexes. In the absence of hydrides, allylic acetates afford conjugated dienes in DMSO solvent.     

Reductive desulfurization of allylic thiols by HS-/H2S in water gives clue to chemical reactions widespread in natural environments

The reduction of allylic thiols to alkenes by hydrogen sulfide in aqueous solutions, a novel reaction that may explain reduction processes widely occurring in natural environments, has been discovered. Its mechanism has been studied and suggested to follow an S(RN)1-like pathway involving radical intermediates undergoing 1,4 hydrogen shifts. [reaction: see text]     

Oxidation of thiols by sodium N-haloarylsulphonamides

The methods for direct titration of thiols with N-haloarylsulphonamides have been evaluated by studying the oxidation of 2-mercaptobenzoic acid, 2-mercaptopropionic acid, 3-mercaptopropionic acid, 2-naphthyl mercaptan, 2-mercaptoethanol, mercaptosuccinic acid, thiophenol, p-chlorothiophenol, butyl mercaptan and monothioglycerol, with chloramine-T (CAT), bromamine-T (BAT) and bromamine-B (BAB). The optimum conditions have been established. The precision was found to be poorer for titrations with CAT. BAB was found to give better precision and accuracy for the determination of all ten thiols studied, and is recommended for use.     

Oxidation of thiols promoted by PhSeZnCl

The ability of PhSeZnCl 1 to catalyze the oxidation of thiols to disulfides has been evaluated and correlated to a catalytic GPx-like activity. The first evidence that vinyl phenylselenides can promote the oxidation of thiols reducing hydrogen peroxide through the formation of a selenoxide intermediate is also reported.     

A Reductive homo-coupling polymerization of aromatic diisocyanates promoted by samarium iodide

The selective reductive homo-coupling polymerization of aromatic diisocyanates via one-electron transfer promoted by samarium iodide in the presence of hexamethylphosphoramide (HMPA) produced the corresponding poly(oxamide)s ( 1 ) nearly quantitatively. The ob-tained polymers were insoluble in common organic solvents. The alkylation of 1 with methyl iodide or allyl bromide in the presence of potassium tert-butoxide provided the highly soluble alkylated polymer in good yields. In either case, the alkylation was almost complete, and both N-and O-alkylation proceeded. The ratio of N-and O-methylation was found to be 64 : 36 by ¹H-NMR spectrum, and that of N- and O-allylation was 3 : 1 from ¹³C-NMR analysis. The present polymerization system could be applied to a variety of diisocyanates, including diphenylmethanediisocyanate (MDI), tolylene 2,6-diisocyanate (TDI), 2,6-naphthyl diisocyanate (NDI) and o-tolidine diisocyanate (TODI). The molecular weights of the polymers were estimated by GPC and found to be 2000–9000. The TGA measurement of the corresponding polymers showed T_d10 at 248–320°C. © 1995 John Wiley & Sons, Inc.     

A Novel Reductive Cyclization of Imides

Imides have been frequently employed as intermediates in the synthesis of bridgehead heterocyclics⁴. Particularly in the synthesis of alkaloids⁵, but also in the preparation of heterocyclic steroids⁶ numerous examples are known. While in general the preparation of an imide is a facile procedure, its cyclization often involves considerable difficulties, notably in case of the substituted sucinimides⁷.     

Alternative chiral thiols for preparation of chiral CdS quantum dots covered immediately by achiral thiols

Developing of alternative chiral thiol stabilizers from the assembly of achiral thiol (e.g. thioglycolic acid) and chiral ligand (e.g. arginine) via both hydrogen bonding and electrostatic interactions was proposed and successfully applied to an efficient preparation of chiral CdS quantum dots (QDs). Chiral CdS QDs capped mainly with achiral thioglycolic acid were also obtained that may allow the chiral QDs to be modified for extended applications.     

A three-component photoreversible tag for thiols

[structure: see text] A one-pot coupling of a 1,3-diketone, an aldehyde, and an alkanethiol has been developed to produce a protected sulfide. Through use of an o-nitrophenylbenzaldehyde, this method provides a one-step route to a photochemically reversible thiol-protecting group. The kinetics of photolysis were established using (1)H NMR analysis, which allows for the rate to be based on the entire reaction scheme.     

Trichloroisocyanuric acid-promoted thiolation of phosphites by thiols

Abstract

A simple and convenient method for the synthesis of thiophosphates by coupling of phosphites with thiols under mild conditions has been developed. The reactions were promoted by trichloroisocyanuric acid (TCCA) and were carried out at room temperature in a one-pot two-step procedure within 20?min. A variety of substrates was tolerated in this method. Notably, both aryl and alkyl thiols could afford the corresponding thiophosphates in good yields.     

Synthesis and biological activity of novel mitomycin C analogs derived from mitomycin A

A variety of mitomycin C analogs were synthesized from mitomycin A and their biological activities were studied. Mitomycin A ( 1 ) underwent nucleophilic displacement reactions involving intramolecular hydrogen migrations upon treatment with nitrogen nucleophiles bearing mobile hydrogens, but the mode of hydrogen migration depended on the nature of the nucleophiles. The reaction with alkoxyamines gave compounds 6 and 7 which have the 5H-6-alkoxyimino-4,7-dione structure in ring A of 1 . However, the reaction with hydroxylamine and benzoylhydrazine afforded compounds 11 and 13 which have the 4-hydroxy-6-hydroxyimino-7-one structure and the 4-hydroxy-6-hydrazono-7-one structure, respectively, in ring A of 1 . These products were converted into various types of mitomycin C derivatives by methylation with methyl iodide or dimethyl sulfate. The mechanistic features of these reactions are discussed. The in vitro and in vivo biological activities were tested by using P388 leukemia and Sarcoma 180 tumor cells. Several of the synthesized compounds exhibited better activity than that of mitomycin C.     

A simple acylation of thiols with anhydrides

Different thiols were efficiently acylated at room temperature with different anhydrides in the presence of potassium carbonate. Chemoselective protection of thiol in the presence of hydroxy group was achieved using di-tert-butyl dicarbonate and isatoic anhydride.     

Reductive 2,6-trans-diallylation of pyridine by triallylborane

Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 11, pp. 2644–2645, November, 1991.     

Reductive hetarylation OF imines by thioxanthene

D. I. Pryanishnikov Perm Agricultural Institute, 614000 Perm. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 1003–1005, July, 1995. Original article submitted December 2, 1994.