Oxidation Of Tertiary Amines Research Articles

RuO4-mediated oxidation of N-benzylated tertiary amines. 3. Behavior of 1,4-dibenzylpiperazine and its oxygenated derivatives

Abstract 1,4-Dibenzylpiperazine (1),-2-piperazinone (7),-2,6-piperazinedione (9), and 1-benzoyl-4-benzylpiperazine (30) were oxidized by RuO4 (generated in situ) by attack at their endocyclic and exocyclic (i.e., benzylic) aminic N-α-C-H bonds to afford various oxygenated derivatives, including acyclic diformamides, benzaldehyde, and benzoic acid. The reaction outcome was complicated by (i) the hydrolysis of diformamides, occurred during the work-up, and (ii) the reaction of benzaldehyde with the hydrolysis-derived amines giving imidazolidines and/or Schiff bases. Benzoic acid resulted from benzaldehyde only. Compounds 7, 30, and 1-benzylpiperazine, but not 9, were transiently formed during the oxidation of 1. In the same reaction conditions, 1,4-dibenzyl-2,3-(or 2,5)-piperazinedione, 1,4-dibenzyl-2,3,6-piperazinetrione, 4-benzyol-1-benzyl-2-piperazinone, and 1,4-dibenzoylpiperazine were inert. The proposed oxidation mechanism involves the formation of endocyclic and exocyclic iminium cations, as well as of cyclic enamines. The latter intermediates probably result by base-induced deprotonation of the iminium cations, provided an N +−β-proton is available. In the case of 1, the cations were trapped with NaCN as the corresponding α-aminonitriles. The statistically corrected regioselectivity (endocyclic/exocyclic) of the RuO4-induced oxidation reaction of 1, 7, and 30 was 1.2–1.3.

Kinetics of Threading α-Cyclodextrin onto Cationic and Zwitterionic Poly(bola-amphiphiles)

The amphiphilic polymers, poly(iminoundecamethylene), poly((N-methylimino)undecamethylene), poly((N,N-dimethylammonio)undecamethylene), and poly((N-methylimino)undecamethylene-N-oxide) were synthesized from nylon-11 by BH3 reduction of amide groups to amino groups and subsequent methylations. The poly(N-oxide) was obtained by H2O2 oxidation of the polymeric tertiary amine. Since the polymers and their inclusion compounds were water-soluble, threading kinetics of α-cyclodextrin rings onto these polymers could be investigated by 1H NMR. Kinetics were fitted by an empirical root exponential association function Y = Y∞(1 − exp(−sqrt(5.3t/t90))). The time t90, necessary to reach 90% completion of the threading process, was taken as a measure of the steric hindrance exerted by the hydrophilic groups along the polymer chain. The vaIues of t90 decreased by more than 3 orders of magnitude as the diameters of the hydrophilic groups decreased from 5.5 to 4.3 Å.

Novel Tertiary Amine Oxide Surfaces That Resist Nonspecific Protein Adsorption

Novel surfaces derivatized with tertiary amine oxides have been prepared and tested for their ability to resist nonspecific protein adsorption. The oxidation of tertiary amines supported on triazine units was carried out using mCPBA to give a format allowing conjugation of biologically active ligands alongside them. Adsorption to these surfaces was tested and compared to adsorption to a set of commercial and custom oligo-/poly(ethylene glycol) (OEG/PEG) supports by challenging them with a protein display library presented on bacteriophage lambda. The new class of amine oxide surfaces is found to compare favorably with the performance of the OEG/PEG supports in the prevention of nonspecific binding.

Further investigation of the N-demethylation of tertiary amine alkaloids using the non-classical Polonovski reaction

The iron salt-mediated Polonovski reaction efficiently N-demethylates certain opiate alkaloids. In this process, the use of the hydrochloride salt of the tertiary N-methyl amine oxide was reported to give better yields of the desired N-demethylated product. Herein, we report further investigation into the use of N-oxide salts in the iron salt-mediated Polonovski reaction. An efficient approach for the removal of iron salts that greatly facilitates isolation and purification of the N-nor product is also described.

Silica‐Supported Vanadium‐Catalyzed N‐Oxidation of Tertiary Amines with Aqueous Hydrogen Peroxide

AbstractA recyclable silica supported vanadium 1 catalyzes the oxidation of tertiray amines to the corresponding N‐oxides with 30% H2O2 in high yield.

Aracyl triflates for preparing fluorescent and UV absorbing derivatives of unreactive carboxylates, amines and other metabolites

Aracyl trifluoromethanesulfonate (triflate) reagents alkylate the unreactive carboxyl groups of betaines. The reagents also derivatise tertiary amines, amine oxides, phosphates and thioethers. A general derivatisation procedure is to dilute the sample with a polar aprotic organic solvent containing a trace of water, followed by adding an appropriate base and the aracyl triflate reagent. Limits of detection were 40 nM for glycine betaine (GB) and carnitine, 0.14 μM for N, N-dimethylglycine, 70 nM for trimethylamine (TMA), and 5.9 μM trimethylamine- N-oxide (TMAO). Limits of detection were improved when derivatisation yield was optimised for different analytes by changing solvent, base and water content of the reaction mixture. Solvents used include acetonitrile, acetone, butanone, dimethoxyethane and dimethoxyethyl ether, with the presence of some water or alcohol tolerated. Suitable bases include the inorganic bases magnesium hydroxide, silver oxide and lithium phosphate. These bases are sparingly soluble in the reaction solvent so sustain weakly basic conditions during derivatisation and can be removed by centrifugation to stop the reaction. This is particularly important for betaine assays since the derivatives are base-sensitive. The information presented here can be used to develop assays for many metabolites using these versatile reagents.

Strategies for the Generation of Molecularly Imprinted Polymeric Nitroxide Catalysts

[reaction: see text] Two strategies for preparing catalytically active molecularly imprinted nitroxide-containing polymers are outlined. Both strategies rely upon the thermal rearrangement chemistry of tertiary amine N-oxides. To this end, several polymers were prepared and the polymeric nitroxides were revealed by oxidation with m-CPBA. All of the resulting polymeric catalysts proved to be competent mediators of the oxidation of alcohols.

Immobilization of methyltrioxorhenium onto tertiary amine and pyridine N-oxide resins

Novel heterogeneous aminated polystyrene and polyacrylate resins and vinylpyridine copolymerized with methylmethacrylate and buthylmethacrylate, were synthesized, characterized and used as supports for MTO immobilization. FTIR, UV–VIS, chemical analysis and 13C NMR indicate that tertiary amine and pyridine N-oxides can act as ligands for MTO anchoring onto polymeric resins. The amount of rhenium incorporated and the interaction between N and Re varied with the ligand type and the polymer. MTO immobilized on oxidized supports was proner to leaching than non-oxidized supports during α-pinene epoxidation with hydrogen peroxide. MTO supported on copolymers were more effective for the latter reaction than MTO supported on tertiary amines or commercial polyvinylpyridine.

Enantioselective Cyanosilylation of Ketones Catalyzed by Double‐Activation Catalysts with N‐Oxides.

AbstractFor Abstract see ChemInform Abstract in Full Text.

RuO4-mediated oxidation of N-benzylated tertiary amines. 2. Regioselectivity for N,N-dimethyl- and N,N-diethylbenzylamine as substrates

RuO4-mediated oxidation of N-benzylated tertiary amines. 2. Regioselectivity for N,N-dimethyl- and N,N-diethylbenzylamine as substrates

Enantioselective cyanosilylation of ketones catalyzed by double-activation catalysts with N-oxides

Enantioselective addition of trimethylsilyl cyanide to ketones by a catalytic double-activation method is described. By combinatorially using 2.0 mol% of a chiral salen-titanium complex and 1.0 mol% of an achiral tertiary amine N-oxide, aromatic, aliphatic and α,β-unsaturated ketones are converted into corresponding cyanohydrin trimethylsilyl ethers with 50–93% yield and 59–86% ee. The effects of ligand structure, catalyst loading and substrate concentration, solvents, the nature of Lewis base, counter ion and other additives, temperature, and substrate structure on the enantioselectivity are discussed. Three possible paths to achieve the asymmetric version of double-activation catalysis and two independent examples of it are proposed.

Bromamine‐T/RuCl3 as an Efficient System for the Oxidation of Tertiary Amines to N‐Oxides.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Oxidation of secondary and tertiary amines by a solid base catalyst

The catalytic oxidation of sec - and tert -amines to nitrones (Eq. (1)), amine N -oxides (Eq. (2)), respectively, is realised by HT- O t Bu catalyst, and benzonitrile as an additive, using 30% hydrogen peroxide at a faster rate in quantitative yields. The catalyst is reused for five recycles without significant loss of activity and selectivity. A novel recyclable protocol is developed for the oxidation of secondary and tertiary amines to nitrones and amine N -oxides, respectively, by Mg-Al- O t Bu hydrotalcite (HT- O t Bu ) catalyst, and benzonitrile as an additive in methanol using 30% hydrogen peroxide at a faster rate in quantitative yields for the first time.

Oxidation of secondary and tertiary amines by a solid base catalyst

Abstract A novel recyclable protocol is developed for the oxidation of secondary and tertiary amines to nitrones and amine N -oxides, respectively, by Mg-Al- O t Bu hydrotalcite (HT- O t Bu ) catalyst, and benzonitrile as an additive in methanol using 30% hydrogen peroxide at a faster rate in quantitative yields for the first time.

Bromamine-T/RuCl 3 as an efficient system for the oxidation of tertiary amines to N-oxides

A variety of tertiary amines were efficiently and selectively oxidized to the corresponding N-oxides by bromamine-T using ruthenium trichloride as catalyst in alkaline (pH 8.4) acetonitrile/water (1:1) at 80 °C.

Oxidation of secondary amines by molecular oxygen and cyclohexanone monooxygenase

Cyclohexanone monooxygenase from Acinetobacter calcoaceticus catalyzed the oxidation of tertiary and secondary amines to N-oxides and nitrones, respectively. The formation of a hydroxylamine intermediate was involved with secondary amines as starting substrates.

Studies into reactions of N-methylmorpholine- N-oxide (NMMO) and its hydrates with cyanuric chloride

The course of the reaction between N-methylmorpholine- N-oxide (NMMO, 1a ) and cyanuric chloride ( 2 ) is strictly dependent on the hydrate water content of the amine oxide. In solid phase, both substances undergo an explosion-like, extremely exothermic reaction. In solution, this process becomes controllable and leads to a quantitative degradation of NMMO into morpholine and formaldehyde, with 2 only acting as an inducing agent. The reaction can be conducted in a way that a clean deoxygenative demethylation is achieved. The monohydrate of NMMO ( 1b ) is quantitatively converted into N-methylmorpholine and hypochlorous acid by the action of 2 . This conversion can be used in synthesis either to deoxygenate tertiary amine N-oxide monohydrates, or to produce chlorohydrins in non-aqueous, organic media in superior yields. The semisesquihydrate of NMMO ( 1c ) reacts with 2 under consumption of water until non-hydrated NMMO is present, which is then further converted into morpholine and HCHO, as in the case of 1a being directly employed as the starting material.

A Partial Synthesis of the Skeleton of Deoxypumiloside, a Putative Intermediate in Camptothecin Biosynthesis

Ajmalicine (3) was used as the starting material for the synthesis of a camptothecin-like skeleton. After C-21 activation through allylic conjugation, regiospecific tertiary amine oxidation was achieved with mercury salts. Subsequent biomimetic oxidation of the indole nucleus then gave quinolone lactam 14. A two-step process finally afforded 4, a close analogue of deoxypumiloside (5), one of the putative intermediates in the biosynthesis of camptothecin.

ChemInform Abstract: Kinetics of Acetonitrile‐Assisted Oxidation of Tertiary Amines by Hydrogen Peroxide

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Oxidation–Cope elimination: a REM-resin cleavage protocol for the solid-phase synthesis of hydroxylamines

We have established that using an oxidation-Cope elimination cleavage protocol allows for the synthesis of N, N-disubstituted hydroxylamines from REM resin (polymer-bound benzyl acrylate). Michael addition of a secondary amine or addition of a primary amine followed by reductive alkylation provides polymer-bound tertiary amines. Oxidation of these resin-bound tertiary amines with MCPBA is followed by concomitant Cope elimination to regenerate the polymer-bound acrylate and provide the cleaved hydroxylamines.