Hydroxylic Reagents Research Articles

Visible light induced palladium catalyzed C[sbnd]H hydroxylation of nitrogen-containing heterocyclic aromatics in the presence of H2O2

A visible-light-induced strategy for the synthesis of phenolic compounds was developed through palladium-catalyzed CH hydroxylation of aromatics with nitrogen-heterocyclic as the directing group and hydrogen peroxide as hydroxylation reagent. Diverse (hetero)arenes with nitrogen-heterocyclic directing groups can be utilized for the ortho CH hydroxylation under mild reaction conditions, and a series of phenolic compounds were synthesized in good yields. The protocol has good functional group tolerance and wide substrate scope, have been successfully applied to the synthesis of natural product caboxamycin and drug deferasirox. According to the experimental results and literature survey, a radical mechanism for the light-induced CH hydroxylation was proposed. This protocol provides a new solution for the preparation of phenolic compounds by CH bond activation hydroxylation.

Radical-anion coupling through reagent design: hydroxylation of aryl halides.

The design and development of an oxime-based hydroxylation reagent, which can chemoselectively convert aryl halides (X = F, Cl, Br, I) into phenols under operationally simple, transition-metal-free conditions is described. Key to the success of this approach was the identification of a reducing oxime anion which can interact and couple with open-shell aryl radicals. Experimental and computational studies support the proposed radical-nucleophilic substitution chain mechanism.

Synthesis of 2‐(2‐Hydroxyaryl)‐4H‐benzo[e][1,3]oxazin‐4‐ones by Palladium‐Catalyzed C(sp2)−H Hydroxylation via Electro‐chemical Oxidation

AbstractAn electrochemical direct ortho‐hydroxylation of 2‐aryl‐4H‐benzo[e][1,3]oxazin‐4‐ones was developed with Pd(OAc)2 as catalyst, oxazine ring as a directing group and Oxone as the hydroxylation reagent. A series of hydroxylation products were obtained under mild conditions, and the yields were from medium to good. This method is characterized by good functional group tolerance and a wide range of substrates. More importantly, use anodic oxidation to avoid the use of potentially toxic and polluting oxidants. A gram‐scale direct electrochemical hydroxylation of 2‐phenyl‐4H‐benzo[e][1,3]oxazin‐4‐one was performed, and the hydroxylation product was applied to synthesize the drug deferasirox. In addition, the single crystal of 2‐(2‐hydroxyphenyl)‐4H‐benzo[e][1,3]oxazin‐4‐one was obtained and determined by X‐ray diffraction. Finally, the reaction mechanism was proposed and verified by cyclic voltammetry (CV). This protocol also provides an alternative electrochemical hydroxylation methodology for the functionalization of molecules.magnified image

TEMPO‐Promoted C(sp3)−H Hydroxylation of 2‐Oxindoles at Room Temperature

Abstract3‐Hydroxy‐2‐oxindoles are valuable biologically active molecules, and efficient methods for their synthesis under mild condition are highly sought after. Here we report a base‐ and metal‐free C(sp3)−H hydroxylation of 2‐oxindoles promoted by commercially available inexpensive TEMPO and atmospheric air as a hydroxylation reagent at room temperature. This protocol provides a mild and simple strategy for the construction of C−O bonds in moderate to good yields with wide functional group tolerance.

A green approach to Fenton chemistry: mono-hydroxylation of salicylic acid in aqueous medium by the electrogeneration of Fenton's reagent

First, the electrochemical characteristics of Fenton's reagent (Fe(III), Fe(II) and hydrogen peroxide), including its catalytic (EC′) behaviour were investigated. Second, the electrogeneration of hydrogen peroxide by a two-electron reduction of dissolved oxygen was conducted at a carbon electrode in a divided electrolysis cell and the concentration of hydrogen peroxide obtained was determined by the titration. The two approaches were then combined to give a one-pot, relatively green approach to aromatic hydroxylation reactions, with the electro-Fenton method allowing the iron to be used catalytically and the oxygen/water employed as the hydroxylation reagent by the in situ production of hydrogen peroxide. In particular, the preparative-scale hydroxylation of salicylic acid has been studied in an oxygen-saturated 0.1 M Na2SO4 pH 3.0 solution containing 5 mM Fe(II) and 5 mM salicylic acid at the controlled potential of −1.0 V vs. SCE. The study showed that after the attack of the hydroxyl radical produced in situ by the electro-Fenton process on salicylic acid, 2,3- and 2,5-dihydroxybenzoic acids were detected as primary monohydroxylated products with the highest yield of ca. 21.6 ± 2.5%.

One‐step Synthesis of Water‐soluble Fullerenols Bearing Nitrogen‐containing Substituents

We found a facile one‐step synthetic method for water‐soluble fullerenols bearing 8–16 nitrogen‐containing substituents as well as more than 16 hydroxyl groups from commercially available C60 as a starting material. The water solubility of one of the products showed the same as the highest one reported (>200 mg/mL). Other fullerenols bearing hydrogen or diethylamino group on the same fullerene cage were also synthesized by the modified method using hydrogen peroxide as a simple hydroxylation reagent.

Catalysts for Monooxygenations Made from Polyoxometalate: An Iron(V)−Oxo Derivative of the Lindqvist Anion

This work uses density functional calculations to design a new high-valent Fe(V)=O catalyst [Mo5O18Fe=O]3-, which is based on the Lindqvist polyoxometalate (Mo6O19(2-)). Because the parent species is stable to oxidative conditions, one may assume that the newly proposed iron-oxo species will be stable, too. The calculated Mössbauer spectroscopic data may be helpful toward an eventual identification of the species. The calculations of C-H hydroxylation and C=C epoxidation of propene show that, if made, [Mo5O18Fe=O]3- should be a potent oxidant that will be subject to strong solvent effect. Moreover, the Lindqvist catalyst leads to an intriguing result; the reaction that starts along an epoxidation pathway with C=C activation ends with a C-H hydroxylation product ((4)6) due to rearrangement on the catalyst. The origins of this result are analyzed in terms of the structure of the catalyst and the electronic requirements for conversion of an epoxidation intermediate to a hydroxylation product. Thus, if made, the [Mo5O18Fe=O]3 will be a selective C-H hydroxylation reagent.

29Si NMR studies on the mechanism of dehydrocoupling of hydrosilanes with hydroxylic reagents in DMF — The role of DMF

Interactions of DMF with hydrosilanes were studied by 29Si NMR. New resonance signals were observed in the 29Si NMR spectra of HMe2SiOSiMe2H and some (alkoxy)hydrosilanes for high ratios of concentrations [DMF]/[H-silane] at 25 °C. The intensities of new signals increased several times at –60 °C. It seems that these new resonances correspond to molecular complexes of DMF with hydrosilanes. The role of DMF in the mechanism of dehydrocoupling of hydrosilanes with hydroxylic reagents in the presence of Zn(II) and Cd(II) halides (X = Cl, Br, I) is discussed. Some common features of the reaction mechanism with the mechanism of hydride transfer from the Si—H bond to the carbenium ion are discussed.Key words: hydrosilanes, hydroxylic reagents, reaction mechanism of dehydrocoupling in DMF, 29Si NMR.

The Solvent Effects on Kinetics and Mechanism of Zinc or Cadmium Halide Catalyzed Reactions of Hydrosilanes with Hydroxylic Reagents

The effect of solvent composition on reaction rates was studied by a kinetic method for reactions of Et3SiH with Ph2Si(OH)2 in the presence of ZnCl2 in a mixture of DMF and THF or Et3SiH with PhCOOH and cadmium bromide CdBr2 in DMF-1,4-dioxane and DMF-THF. A decrease in reaction rates with decreasing polarity of the medium (and its dielectric constant) has been observed. The kinetic order of dehydrocoupling reaction with respect to DMF was determined from kinetic studies. The constants of nucleophilic catalysis with DMF (λ) were found. The role of DMF in the mechanism of dehydrocoupling of hydrosilanes with hydroxylic reagents in the presence of ZnX2 and CdX2 halides (X = Cl, Br, I) is discussed.

ChemInform Abstract: Vinyl and Alkynyl Pyrimidines as Michael Acceptors: An Approach to a Cylindrospermopsin Substructure.

Vinyl pyrimidine 9 and alkynyl pyrimidine 24 undergo base-mediated intramolecular conjugate addition reactions in which a carbamate and a urea, respectively, behave as nitrogen nucleophiles. The cyclic carbamate derived from 9 was converted to 11 via a metalation-oxidation reaction in which 2-phenylsulfonyl-3-phenyloxaziridine behaves as a hydroxylation reagent. The cyclic urea derived from 24 was converted to cylindrospermopsin substructure 30 using dimethyldioxirane to introduce the C(7) hydroxyl group.

Vinyl and alkynyl pyrimidines as michael acceptors: an approach to a cylindrospermopsin substructure.

Vinyl pyrimidine 9 and alkynyl pyrimidine 24 undergo base-mediated intramolecular conjugate addition reactions in which a carbamate and a urea, respectively, behave as nitrogen nucleophiles. The cyclic carbamate derived from 9 was converted to 11 via a metalation-oxidation reaction in which 2-phenylsulfonyl-3-phenyloxaziridine behaves as a hydroxylation reagent. The cyclic urea derived from 24 was converted to cylindrospermopsin substructure 30 using dimethyldioxirane to introduce the C(7) hydroxyl group.

Synthesis of Spiroketals Related to Griseusin A

The synthesis and attempted functionalization of the spiroketal ring system of the naturally occurring pyranonaphthoquinone antibiotic griseusin A 1 is reported. The unsaturated spiroketals 5,6 were prepared from furonaphthopyran 22, which in turn was constructed from furonaphthofuran 20. Addition of 2-trimethylsilyloxyfuran 13 to quinone 19 afforded furonaphthofuran 20. Initial work using acetylenic quinone 12 afforded a pentacyclic product 15, where a third Michael reaction of the phenolic hydroxyl group with the α,β-unsaturated ketone moiety had occurred. Modified reaction conditions afforded trimethylsilyl analogue 16. Naphthoquinone 19, which bears a 2-alkenyl side chain rather than an acetylene, was synthesized using similar methodology to 12 and subsequently converted to furonaphthofuran adduct 20. Ceric ammonium nitrate oxidative rearrangement of 20 produced diol 22, which was then cyclized to spiroketals 5,6 under acidic conditions. Reaction of spiroacetals 5,6 with osmium tetroxide did not effect the desired hydroxylation of the olefin. Use of cetyltrimethylammonium permanganate as the hydroxylation reagent resulted in reaction with the C5a-C11a double bond affording diols 24,25.

Synthesis of trimethylsilyloxy and hydroxy compounds from carbanions and bis (trimethylsilyl)peroxide

The reactions of bis (trimethylsilyl) peroxide with alkyl, vinyl, alkynyl, aromatic and heteroaromatic anions are described. Depending on the reaction conditions, the trimethylsilyloxy derivatives can be obtained alone or together with the corresponding trimethylsilyl derivatives, which is sometimes the major product. Enolates, generated using magnesium diisopropylamide give the corresponding hydroxycarbonyl compounds in good yields. An attempt to rationalise the above results is given, emphasising the wide use of bis(trimethylsilyl)peroxide in organic synthesis as an electrophilic hydroxylation reagent.

Flash photolysis studies of nitrile imines and related intermediates photogenerated from sydnones and tetrazoles in fluid solutions

The spectral and kinetic behavior of nitrile imines photogenerated from sydnones and tetrazoles in fluid solutions has been studied by laser and lamp flash photolysis. The nitrile imines are characterized by lifetimes of milliseconds and are quenchable by the dipolarophile dimethyl acetylenedicarboxylate ( k q = (5 – 9) × 10 3 M −1 s −1 for N,C-diarylnitrile imines in benzene) and by carboxylic acids ( k q = 10 8 - (2 × 10 9) M −1 s −1 with trifluoroacetic acid in benzene and acetonitrile). The phototransformation of 3,4-diaryl-sydnones to the corresponding N,C-diarylnitrile imines occurs rapidly (within nanoseconds of laser excitation); this suggests that bicyclic diaziridine, diazirine or 1,2,3-oxadiazolin-5-one intermediates, postulated in the literature as precursors for nitrile imines, are either very short lived or not involved at all. The laser flash photolysis of the sydnones unsubstituted at the 4-position or bearing a methyl group at this position gives rise to additional, fast-decaying, transient species (τ = 0.3 – 4 μs in benzene) which become progressively longer lived upon interaction with hydroxylic reagents (water, alcohols and carboxylic acids). Possible assignments of these transient species in terms of ylide structures are discussed in the light of the results of steady state photolysis at low temperatures.

General base catalysis of the addition of hydroxylic reagents to unstable carbocations and its disappearance

Etude de la catalyse basique generale de l'addition d'alcools aux carbocations aryl-1 ethyles

Titanocene and zirconocene dichloride derivatives with hydroxylic reagents

The reaction of Cp 2TiCl 2 (Cp = C 5H 5) with ethanol in the presence of Et 3N in acetonitrile yields the derivatives CpTiCl(OEt) 2 or CpTiCl 2(OEt). Similar reactions of Cp 2MCl 2 (M = Ti or Zr) with glycols (GH 2 = 1,2-propanediol, 2,3-butanediol, pinacol or hexylene glycol) or fluoro-β-diketones (KeH = hexafluoroacetylacetone(hfa), benzoyltrifluoroacetone (bta) or 2-thenoyltrifluoroacetone (tta)) gave CpMCl(G) or CpMCl(Ke) 2.

The effect of the reactivity of hydroxylic reagents on the properties of crosslinked polyetherurethane elastomers

The kinetics of three-dimensional polymerization in the synthesis of spatially linked polyetherurethanes has been studied and it has been shown that, because the OH groups of the tetrahydrofuran-propylene oxide copolymer differ in their reactivity from those of trimethylolpropane, gel-formation does not occur in the absence of a catalyst at an OH-group concentration from the trimethylolpropane of 0·40 g·equiv/l. The introduction of the catalyst and an increase in its concentration makes it possible to level out the activities of the copolymer's and the triol's OH groups and to obtain a spatially-linked polyetherurethane with outstanding physical and mechanical properties.

Rearrangement of N-cyano-anthranilic acids to 1,2-dihydro-2-imino-3,1,4H-benzoxazin-4-ones and 2,4(IH,3H)-quinazoline-diones. Reactions of 1,2-dihydro-2-imino-3,1,4H-benzoxazin-4-one with hydroxylic reagents.

Rearrangement of N-cyano-anthranilic acids to 1,2-dihydro-2-imino-3,1,4H-benzoxazin-4-ones and 2,4(IH,3H)-quinazoline-diones. Reactions of 1,2-dihydro-2-imino-3,1,4H-benzoxazin-4-one with hydroxylic reagents.

Mechanism of substitution at a saturated carbon atom. Part XXXIX. Nucleophilic substitutions in tertiary alkyl halides by hydroxylic reagents in nitromethane solvent

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