Oxidation Of Pyrroles Research Articles

Unusual Regio‐ and Chemoselectivity in Oxidation of Pyrroles and Indoles Enabled by a Thianthrenium Salt Intermediate

AbstractA dearomative oxidation of pyrroles to Δ3‐pyrrol‐2‐ones is described, which employs a sulfoxide as oxidant, in conjunction with a carboxylic acid anhydride and a Brønsted acid additive. 3‐substituted pyrroles undergo regioselective oxidation to give the product isomer in which oxygen has been introduced at the more hindered position. Regioselectivity is rationalized by a proposed mechanism that proceeds by initial thianthrenium introduction at the less‐hindered pyrrole α‐position, followed by distal attack of an oxygen nucleophile and subsequent elimination of thianthrene. The same reaction conditions are also able to effect a chemoselective oxidation of indoles to indolin‐3‐ones and additionally of indolin‐3‐ones to 2‐hydroxyindolin‐3‐ones. Here again, the regio‐ and chemoselectivities are rationalized through the intermediacy of a thianthrenium salt.

Unusual Regio- and Chemoselectivity in Oxidation of Pyrroles and Indoles Enabled by a Thianthrenium Salt Intermediate.

A dearomative oxidation of pyrroles to Δ3-pyrrol-2-ones is described, which employs a sulfoxide as oxidant, in conjunction with a carboxylic acid anhydride and a Brønsted acid additive. 3-substituted pyrroles undergo regioselective oxidation to give the product isomer in which oxygen has been introduced at the more hindered position. Regioselectivity is rationalized by a proposed mechanism that proceeds by initial thianthrenium introduction at the less-hindered pyrrole α-position, followed by distal attack of an oxygen nucleophile and subsequent elimination of thianthrene. The same reaction conditions are also able to effect a chemoselective oxidation of indoles to indolin-3-ones and additionally of indolin-3-ones to 2-hydroxyindolin-3-ones. Here again, the regio- and chemoselectivities are rationalized through the intermediacy of a thianthrenium salt.

Chemical Structure Regulates the Formation of Secondary Organic Aerosol and Brown Carbon in Nitrate Radical Oxidation of Pyrroles and Methylpyrroles.

Nitrogen-containing heterocyclic volatile organic compounds (VOCs) are important components of wildfire emissions that are readily reactive toward nitrate radicals (NO3) during nighttime, but the oxidation mechanism and the potential formation of secondary organic aerosol (SOA) and brown carbon (BrC) are unclear. Here, NO3 oxidation of three nitrogen-containing heterocyclic VOCs, pyrrole, 1-methylyrrole (1-MP), and 2-methylpyrrole (2-MP), was investigated in chamber experiments to determine the effect of precursor structures on SOA and BrC formation. The SOA chemical compositions and the optical properties were analyzed using a suite of online and offline instrumentation. Dinitro- and trinitro-products were found to be the dominant SOA constituents from pyrrole and 2-MP, but not observed from 1-MP. Furthermore, the SOA from 2-MP and pyrrole showed strong light absorption, while that from 1-MP were mostly scattering. From these results, we propose that NO3-initiated hydrogen abstraction from the 1-position in pyrrole and 2-MP followed by radical shift and NO2 addition leads to light-absorbing nitroaromatic products. In the absence of a 1-position hydrogen, NO3 addition likely dominates the 1-MP chemistry. We also estimate that the total SOA mass and light absorption from pyrrole and 2-MP are comparable to those from phenolic VOCs and toluene in biomass burning, underscoring the importance of considering nighttime oxidation of pyrrole and methylpyrroles in air quality and climate models.

Oxidative Cleavage of Indoles Mediated by Urea Hydrogen Peroxide or H2O2 in Polar Solvents

AbstractThe oxidative cleavage of indoles (Witkop oxidation) involving the use of H2O2 or urea hydrogen peroxide in combination with a polar solvent has been described. Among these solvents, 1,1,1,3,3,3‐hexafluoroisopropanol (HFIP) stands out as the one affording the corresponding 2‐ketoacetanilides generally in higher yields The protocol described has also enabled the oxidation of different pyrroles and furans derivatives. Furthermore, the procedure was implemented in a larger‐scale and HFIP was distilled from the reaction mixture and reused (up to 4 cycles) without a significant detriment in the reaction outcome, which remarks its sustainability and applicability.magnified image

Oxidation of Pyrrole by Dehaloperoxidase-Hemoglobin: Chemoenzymatic Synthesis of Pyrrolin-2-Ones.

The use of oxidoreductases as biocatalysts in the syntheses of functionalized, monomeric pyrroles has been a challenge owing to, among a number of factors, undesired polypyrrole formation. Here, we have investigated the ability of dehaloperoxidase (DHP), the coelomic hemoglobin from the terebellid polychaete Amphitrite ornata, to catalyze the H2O2-dependent oxidation of pyrroles as a new class of substrate for this enzyme. Substrate oxidation was observed for all compounds employed (pyrrole, N-methylpyrrole, 2-methylpyrrole, 3-methylpyrrole and 2,5-dimethylpyrrole) under both aerobic and anaerobic conditions. Using pyrrole as a representative substrate, only a single oxidation product, 4-pyrrolin-2-one, was observed, and notably without formation of polypyrrole. Reactivity could be initiated from all three biologically relevant oxidation states for this catalytic globin: ferric, ferrous and oxyferrous. Isotope labeling studies determined that the O-atom incorporated into the 4-pyrrolin-2-one product was derived exclusively from H2O2, indicative of a peroxygenase mechanism. Consistent with this observation, single- and double-mixing stopped-flow UV-visible spectroscopic studies supported Compound I, but not Compounds ES or II, as the catalytically-relevant ferryl intermediate involved in pyrrole oxidation. Electrophilic addition of the ferryl oxygen to pyrrole is proposed as the mechanism of O-atom transfer. The results demonstrate the breadth of chemical reactivity afforded by dehaloperoxidase, and provide further evidence for establishing DHP as a multifunctional globin with practical applications as a biocatalyst.

Elaboration and characterization of carboxylic acid-functionalized polypyrrole films

Conducting polymers such as polypyrrole and its derivatives are highly attractive for a number of applications including biology, sensing and molecular electronics. For these purposes, poly(N-carboxyalkylpyrroles) are of interest since they contain a terminal carboxyl group that can be easily modified with biological or chemical moieties. In the present study, pyrrole monomers were modified by grafting, on the N-position of the pyrrole monomer, of an alkyl chain, whose length varied from 1 to 10 carbons, terminated by a carboxyl group. The substitution significantly decreased the solubility of the monomers but it was although possible to solubilize them in acetonitrile. So, the anodic oxidation of these N-substituted pyrroles was performed in acetonitrile leading to the electrodeposition of substituted polypyrrole films. The morphological features (topography, thickness, roughness) were determined and compared with the ones of polypyrrole and poly(N-alkylpyrroles) having the same chain length. The morphology of the polymer films was shown to be strongly dependent on the alkyl chain since non-substituted polypyrrole exhibited granular structure when substituted ones had a fibrillar structure. The substitution also significantly impacts on the wettability of the films because an increase of the substituted chain length led to the increase of the hydrophobicity of poly(N-carboxyalkylpyrroles).

Oxidation properties of β-substituted pyrroles

Pyrroles represent building blocks of conjugated poly(heterocycles) which, as organic conductors, are potential materials for organic electronics. Oxidation of β-substituted pyrroles constitutes an important first step in the process of electropolymerization. Ionization energy and the electron spin density distribution are two the most important properties regarding monomers. These properties are studied as a function of electron-withdrawing and electron-donating substituents of pyrrole ring. Evolution of molecular structure, nature of bonding, and electronic density are studied as an effect of ionization process.

The Oxidation of Pyrrole.

The dearomatization of heterocycles has been a powerful means for producing functional molecules in synthesis. In the case of pyrroles, reductive methods (such as the Birch reduction) have been most widely exploited, while oxidative methods are generally dismissed as too difficult or unpredictable to be useful. However, since the early twentieth century considerable research has been carried out on the controlled oxidation of pyrroles to give highly functionalized products, using a variety of oxidants. This review presents a summary of all work up until the present day in the area of pyrrole oxidation, looking at the use of peroxide, singlet oxygen, hypervalent iodine reagents, a range or organic and inorganic oxidants, and electrochemical approaches. It also offers some perspective on the potential future role of pyrrole oxidation in synthesis.

ChemInform Abstract: Controlled Oxidation of Pyrroles: Synthesis of Highly Functionalized γ‐Lactams.

AbstractThis special oxidation method of pyrroles is performed with an excess of Dess—Martin periodinane avoiding polymerization and decomposition usually observed for this process.

Controlled Oxidation of Pyrroles: Synthesis of Highly Functionalized γ-Lactams

The oxidation of pyrroles usually leads to uncontrolled polymerization and decomposition. To overcome this problem, the controlled oxidation of substituted pyrroles with Dess-Martin periodinane is reported. This strategy yields a range of 5-aroyloxypyrrolinones.

Chemo- and regioselectivity in the reactions of polyfunctional pyrroles

The chemo- and regioselectivity of the reduction, oxidation and Wittig reaction of polyfunctional pyrroles, containing a variety of reactive centres was investigated. The reaction of 3,5-dichloropyrrole-2,4-dicarboxaldehydes with potassium permanganate leads to regioselective oxidation of the 2-formyl group, while the Wittig reaction with 1 equiv of a triphenylphosphorane produced the 2-alkenyl substituted pyrroles.

Singlet oxygen oxidation of pyrroles. Formation of 5-substituted derivatives

The tert-butyl ester of 3-methoxy-2-pyrrolecarboxylic acid 3 undergoes reaction with singlet oxygen to form an intermediate imino hydroperoxide 4. This hydroperoxide may be trapped by a variety of nucleophiles yielding 5-substituted pyrroles 6. With strong nucleophilic substituents at the 5-position, these pyrroles may add to unreacted hydroperoxide 4 to form bipyrrole-like products 7.

Singlet oxygen in synthesis. Formation of d, l- and meso-isochrysohermidin from a 3,3′-bipyrrole precursor

A synthesis of the d, l and meso forms of isochrysohermidin 3 is outlined which employs the singlet oxygen oxidation of pyrroles as the key step. The bipyrrole precursor 8 was synthesized from a 3-hydroxy monopyrrole which, in turn, was prepared by addition of methylamine to a vinyl vicinal tricarbonyl.

Singlet oxygen oxidation of pyrroles: Synthesis and chemical transformations of novel 4,4-bis(trifluoromethyl)imidazoline analogs

A novel singlet oxygen ring cleavage of pyrrole 5a and subsequent acid-catalyzed facile dehydrocyclization afforded a new series of 4,4-bis(trifluoromethyl)imidazolines with a p-fluorophenacyl side chain at the 5-position, which have shown potent acyl CoA: cholesterol acyltransferase (ACAT) and cholesterol biosynthesis inhibitory activities.

Electrogeneration of a New Family of Ionophoric Resins. Anodic Oxidation of N-Polyethereal Pyrroles

Electrogeneration of a New Family of Ionophoric Resins. Anodic Oxidation of N-Polyethereal Pyrroles

A chemical investigation of shale oil ageing

Chemical changes resulting from exposure of Stuart and Nagoorin (Queensland, Australia) Fischer assay oils to oxygen at 45 °C for 4000 h were investigated by n.m.r., g.c.-m.s. and potentiometric titration techniques. The most significant reactions, which were all accelerated by visible light, involved oxidation of alkenes, phenols and pyrroles. A possible mechanism of gum formation is given.

Oxidation of pyrroles with benzoyl peroxide: Synthesis of mono- and dihydroxypyrrole O-benzoates and oxidative cleavage of pyrrole-2-methanols.

Oxidation of pyrroles with benzoyl peroxide: Synthesis of mono- and dihydroxypyrrole O-benzoates and oxidative cleavage of pyrrole-2-methanols.

Oxidation of Pyrroles with Benzoyl Peroxide

Oxidation of Pyrroles with Benzoyl Peroxide

Reactions of 2-amino-2-deoxy- D-glucose with benzoylacet-aldehyde and 1-phenyl-1,3-butanedione

2-Amino-2-deoxy- D-glucose reacts with benzoylacetaldehyde and 1-phenyl-1,3-butanedione to yield 2-deoxy-2-[1-(3-oxo-3-phenyl-1-propenyl)amino]- D-glucose ( 5) and 2-deoxy-2-[2-(4-oxo-4-phenyl-2-butenyl)amino]- D-glucose ( 6), respectively. Acetylation of these substances affords 1,3,4,6-tetra- O-acetyl-2-deoxy-2-[1-(3-oxo-3-phenyl-1-propenyl)amino]-α- D-glucopyranose ( 8) and 1,3,4,6-tetra- O-acetyl-2-deoxy-2-[2-(4-oxo-4-phenyl-2-butenyl)amino]-α- D-glucopyranose ( 9), whose structures are established on the basis of their i.r. and p.m.r. spectra, and hydrolysis to 1,3,4,6-tetra- O-acetyl-2-amino-2-deoxy-α- D-glucopyranose hydrochloride. Cyclisation of enamines 5 and 6 yields 4-benzoyl-2-( D- arabino-tetrahydroxybutyl)pyrrole ( 11) and 3-benzoyl-5-( D- arabino-tetrahydroxybutyl)-2-methylpyrrole ( 12) respectively. Treatment of compound 5 at pH 9–10 gives the (tetrahydroxybutyl)pyrrole ( 11) and 3-benzoylpyrrole. Oxidation of pyrroles 11 and 12 with sodium periodate (or lead tetraacetate) yields 4-benzoyl-2-pyrrolecarboxaldehyde ( 13) and 4-benzoyl-5-methyl-2-pyrrolecarboxaldehyde ( 14), respectively, which can be subsequently oxidized to the corresponding 2-pyrrolecarboxylic acids ( 15) and ( 16). 1,3,4,6-Tetra- O-acetyl-2-amino-2-deoxy-α- D-glucopyranose hydrochloride can be readily prepared by hydrolysis of 1,3,4,6-tetra- O-acetyl-2-deoxy-2-[2-(4-oxo-2-pentenyl)amino]-α- D-glucopyranose ( 10).