Dioxygenase-catalysed oxidation of alkylaryl sulfides: sulfoxidation versus cis-dihydrodiol formation

Toluene- and naphthalene-dioxygenase-catalysed sulfoxidation of nine disubstituted methylphenyl sulfides, using whole cells of Pseudomonas putida, consistently gave the corresponding enantioenriched sulfoxides. Using the P. putida UV4 mutant strain, and these substrates, differing proportions of the corresponding cis-dihydrodiol sulfides were also isolated. Evidence was found for the concomitant dioxygenase-catalysed cis-dihydroxylation and sulfoxidation of methyl para-tolyl sulfide. A simultaneous stereoselective reductase-catalysed deoxygenation of (S)-methyl para-tolyl sulfoxide, led to an increase in the proportion of the corresponding cis-dihydrodiol sulfide. The enantiopurity values and absolute configurations of the corresponding cis-dihydrodiol metabolites from methyl ortho- and para-substituted phenyl sulfides were determined by different methods, including chemoenzymatic syntheses from the cis-dihydrodiol metabolites of para-substituted iodobenzenes. Further evidence was provided to support the validity of an empirical model to predict, (i) the stereochemistry of cis-dihydroxylation of para-substituted benzene substrates, and (ii) the regiochemistry of cis-dihydroxylation reactions of ortho-substituted benzenes, each using toluene dioxygenase as biocatalyst.     

Dioxygenase-catalysed oxidation of monosubstituted thiophenes: sulfoxidation versus dihydrodiol formation

Toluene dioxygenase (TDO)-catalysed sulfoxidation, using Pseudomonas putida UV4, was observed for the thiophene substrates 1A-1N. The unstable thiophene oxide metabolites, 6A-6G, 6K-6N, spontaneously dimerised yielding the corresponding racemic disulfoxide cycloadducts 7A-7G, 7K-7N. Dimeric or crossed [4 + 2] cycloaddition products, derived from the thiophene oxide intermediates 6A and 6D or 6B and 6D, were found when mixtures of thiophene substrates 1A and 1D or 1B and 1D were biotransformed. The thiophene sulfoxide metabolite 6B was also trapped as cycloadducts 17 or 18 using stable dienophiles. Preferential dioxygenase-catalysed oxidation of the substituent on the thiophene ring, including exocyclic sulfoxidation (1H-1J) and cis-dihydroxylation of a phenyl substituent (1G and 1N), was also observed. An enzyme-catalysed deoxygenation of a sulfoxide in P. putida UV4 was noticed when racemic disulfoxide cyclo-adducts 7A, 7B and 7K were converted to the corresponding enantioenriched monosulfoxides 8A, 8B and 8K via a kinetic resolution process. The parent thiophene 1A and the 3-substituted thiophenes 1K-1N were also found to undergo ring dihydroxylation yielding the cis/trans-dihydrodiol metabolites 9A and 9K-9N. Evidence is provided for a dehydrogenase-catalysed desaturation of a heterocyclic dihydrodiol (9Kcis/9Ktrans) to yield the corresponding 2,3-dihydroxythiophene (24) as its preferred thiolactone tautomer (23). A simple model to allow prediction of the structure of metabolites, formed from TDO-catalysed bacterial oxidation of thiophene substrates 1, is presented.     

Dioxygenase-catalysed cis-dihydroxylation of meta-substituted phenols to yield cyclohexenone cis-diol and derived enantiopure cis-triol metabolites

cis-Dihydroxylation of meta-substituted phenol (m-phenol) substrates, to yield the corresponding cyclohexenone cis-diol metabolites, was catalysed by arene dioxygenases present in mutant and recombinant bacterial strains. The presence of cyclohexenone cis-diol metabolites and several of their cyclohexene and cyclohexane cis-triol derivatives was detected by LC-TOFMS analysis and confirmed by NMR spectroscopy. Structural and stereochemical analyses of chiral ketodiol bioproducts, was carried out using NMR and CD spectroscopy and stereochemical correlation methods. The formation of enantiopure cyclohexenone cis-diol metabolites is discussed in the context of postulated binding interactions of the m-phenol substrates at the active site of toluene dioxygenase (TDO).     

Aerobic oxidation of secondary benzylic alcohols and direct oxidative amidation of aryl aldehydes promoted by sodium hydride

We reported herein new reactivities and possible mechanistic implications of a simplest oxidant (NaH/air) uncovered on a broad range of useful transformations, including aerobic alcohol oxidations, allylic alcohol isomerizations and oxidations, cyclopropyl alcohol fragmentations, and direct aryl aldehyde oxidative amidations. These readily implementable transition-metal-free processes feature exceptional material accessibility, operational simplicity, and environmental compatibility, and add new dimensions to its synthetic utilities that are fairly robust yet had not previously been fully realized and systematically explored.     

Photolysis of aryl bromides and aryl chlorides in benzene

Conclusions As a result of photolysis of aromatic bromo- and chlorohydrocarbons in benzene solution, products of replacement of the halogen atoms by a phenyl group were obtained.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 2, pp. 456–457, February, 1967.     

Regioselectivity and stereoselectivity of dioxygenase catalysed cis-dihydroxylation of mono- and tri-cyclic azaarene substrates

cis-Dihydrodiol metabolites were obtained from dioxygenase-catalysed asymmetric dihydroxylations of five monocyclic (azabiphenyl) and four tricyclic (azaphenanthrene) azaarene substrates. Enantiopurity values and absolute configuration assignments were determined using a combination of stereochemical correlation, X-ray crystallography and spectroscopy methods. The degree of regioselectivity found during cis-dihydroxylation of monocyclic azaarenes (2,3 bond > 3,4 bond) and of tricyclic azaarenes (bay region > non-bay region bonds) was dependent on the type of dioxygenase used. The cis-dihydrodiol metabolite from an azaarene (3-phenylpyridine) was utilised in the chemoenzymatic synthesis of the corresponding trans-dihydrodiol.     

Mutual effect of benzene and maleic anhydride in selective heterogeneous catalytic oxidation of benzene

It is shown that in the oxidation of benzene (B) by molecular oxygen over a vanadium-molybdenum oxide catalyst the introduction of maleic anhydride (MA) into the reaction mixture suppresses the formation of carbon oxides but does not alter the rate for formation of MA from B. It has been found by programmed thermal desorption that B and MA are adsorbed at different active sites on the catalyst.Translated from Teoreticheskaya i Éksperimental'naya Khimiya, Vol. 24, No. 5, pp. 622–626, September–October, 1988.We thank Yu. I. Pyatnitskii for discussion of the paper.     

Efficient oxidation of benzylic alcohols with [hydroxy(tosyloxy)iodo]benzene under microwave irradiation

An efficient method for the oxidation of benzylic alcohols with [hydroxy(tosyloxy)iodo]benzene under solvent-free microwave irradiation conditions is described.     

氯对苯氧化过程影响机制的实验研究

针对高含氯垃圾气化-燃烧工艺中焦油的氧化裂解过程,利用均相管流反应器配合傅里叶红外光谱仪,以C_6H_6为焦油模型化合物,对比研究了氯参与前后,裂解产物组成和氧化完全程度随温度和当量比的变化,探索了氯对C_6H_6氧化裂解过程的影响机制。结果表明,低温下氯对C_6H_6的氧化有明显的激发作用,但由于氯对OH的消耗,对裂解产物进一步转化为完全氧化产物CO_2又存在抑制作用。此外,在高温低当量比条件下氯对聚合反应也有促进作用。因此,在工程应用中,高含氯垃圾气化产物的燃烧可适应更低的温度,但应避免高温低当量比反应环境的形成以避免聚合产物。此外,还应控制垃圾原料中的氯元素比例,以保障氧化反应的充分进行。     

Anodic oxidation of mono- and disubstituted 1,4-dimethoxybenzenes

The electrochemical oxidation of mono- and disubstituted 1,4-dimethoxybenzene derivatives with zero, one, and two benzylic CH(2)X groups (X = OAc, Cl, OH) (5a-c and 6a-c) has been carried out by using both constant-current and controlled-potential techniques in methanol and in the presence of different electrolytes and working electrodes. Constant-current electrolysis in KOH-methanol solutions yielded mostly the corresponding 1,4-quinone derivatives from 5a-c and 6b, whereas the disubstituted 1,4-dimethoxybenzenes 6a,c underwent side-chain oxidation to form 2,5-dimethoxyterephthalaldehydes. Upon alteration of the medium from the commonly used basic KOH-methanol to neutral LiClO(4)-methanol, a new spectrum of products was achieved in most cases, involving novel coupling products from monosubstituted substrates and quinone derivatives from disubstituted ones. Controlled-potential oxidation at the glassy carbon anodes and in a neutral LiClO(4)-methanol medium led to more complex mixtures of products, namely, polymers and new coupling products from monosubstituted substrates and quinones and side-chain oxidation (or substitution) products from the disubstituted ones. Three new coupling products were isolated and characterized by X-ray measurements.     

A remarkable effect of ionic liquids in transition-metal-free aerobic oxidation of benzylic alcohols

The transition-metal-free aerobic oxidation of benzylic alcohols is uniquely accelerated by a 1-butyl-3-methylimidazolium hexafluorophosphate (BMI-PF₆)/PhCF₃ biphasic system and Cs₂CO₃ to afford the corresponding ketones in good yields. The reaction system is also applicable to an oxidative cross-esterification of primary benzyl alcohols with a higher aliphatic alcohol.     

Substituent effects in mass spectrometry—II. The effect of substituents on the dissociation of para and meta disubstituted benzenes

The effect of substituents on the activation energy for primary dissociation processes in the molecular ions of mono- and para and meta di-substituted benzenes has been examined. Where the daughter ion retains the substituent group, variation of the energy of activation derives from a combination of the effects of substituents on the ionisation potential of the molecular ion and the appearance potential of the daughter ion. An equation relating the energy of activation for the fragmentation of the molecular ion of a mono-substituted benzene to that of related para and meta di-substituted benzenes is presented.     

Iron-catalyzed arylation or aroylation of benzothiazoles with benzylic alcohols and aryl ketones

An iron-catalyzed arylation or aroylation of benzothiazoles with alcohols and aryl ketones via an in situ cross-trapping strategy has been described. Both the use of an iron catalyst and the ratio of substrates are important for this transformation, and this reaction is sensitive to the electronic effects of the substituents.     

Simple and efficient nickel-catalyzed cross-coupling reaction of alkynylalanes with benzylic and aryl bromides

Highly efficient and simple coupling reactions of benzylic and aryl bromides with aluminium acetylide catalyzed by NiCl(2)(PPh(3))(2) are reported. The coupling reactions proceed at room temperature employing 4 mol% catalyst, affording coupling products in excellent yields of up to 95% in short reaction times. The system worked efficiently with aryl and heterocyclic bromides as well.     

Origin of the SN2 benzylic effect

The S N2 identity exchange reactions of the fluoride ion with benzyl fluoride and 10 para-substituted derivatives (RC6H 4CH 2F, R = CH3, OH, OCH 3, NH2, F, Cl, CCH, CN, COF, and NO2) have been investigated by both rigorous ab initio methods and carefully calibrated density functional theory. Groundbreaking focal-point computations were executed for the C6H5CH 2F + F (-) and C 6H 5CH2Cl + Cl (-) SN2 reactions at the highest possible levels of electronic structure theory, employing complete basis set (CBS) extrapolations of aug-cc-pV XZ (X = 2-5) Hartree-Fock and MP2 energies, and including higher-order electron correlation via CCSD/aug-cc-pVQZ and CCSD(T)/aug-cc-pVTZ coupled cluster wave functions. Strong linear dependences are found between the computed electrostatic potential at the reaction-center carbon atom and the effective SN2 activation energies within the series of para-substituted benzyl fluorides. An activation strain energy decomposition indicates that the SN2 reactivity of these benzylic compounds is governed by the intrinsic electrostatic interaction between the reacting fragments. The delocalization of nucleophilic charge into the aromatic ring in the SN2 transition states is quite limited and should not be considered the origin of benzylic acceleration of SN2 reactions. Our rigorous focal-point computations validate the benzylic effect by establishing SN2 barriers for (F (-), Cl (-)) identity exchange in (C6H5CH2F, C6H 5CH2Cl) that are lower than those of (CH3F, CH3Cl) by (3.8, 1.6) kcal mol (-1), in order.     

A new method for the selective oxidation of allylic and benzylic alcohols

A new method is described for the selective oxidation of allylic or benzylic alcohols, in the presence of saturated alcohols, using trimethylamine-N-oxide in the presence of an iron carbonyl.     

Selective aerobic oxidation of benzylic amines to aryl nitriles catalyzed by CuBr2/N-methyl imidazole

A convenient and efficient copper-catalyzed aerobic oxidation of primary amines to aryl nitriles was described. Various benzylic and allylic amines were selectively oxidized to the corresponding nitriles in high yields using CuBr₂/NMI as the catalyst and O₂ as the oxidant. The oxidation reaction profiles monitored by ¹H NMR disclosed the scenario of the reaction path as well as the role of the additives. The addition of NMI increased the rate of reaction and suppressed the hydrolysis and the deamination.     

Rhodium/tris-binaphthyl chiral monophosphite complexes: Efficient catalysts for the hydroformylation of disubstituted aryl olefins

A family of threefold symmetry phosphite ligands, P(O–BIN–OR)₃ (BIN = 2,2′-binaphthyl; R = Me, Bn, CHPh₂, 1-adamantyl), derived from enantiomerically pure (R)-BINOL, was developed. Cone angles within the range 240–270° were calculated for the phosphite ligands, using the computational PM6 Hamiltonian. Their rhodium complexes formed in situ showed remarkable catalytic activity in the hydroformylation of hindered phenylpropenes, under relatively mild reaction conditions, with full chemoselectivity for aldehydes, high regioselectivity, however with low enantioselectivity. The ether substituents at the ligand affected considerably the catalytic activity on the hydroformylation of 1,1- and 1,2-disubstituted aryl olefins. The kinetics of the hydroformylation of trans-1-phenyl-1-propene, using tris[(R)-2′-benzyloxy-1,1′-binaphthyl-2-yl]phosphite as model ligand, was investigated. A first order dependence in the hydroformylation initial rate with respect to substrate and catalyst concentrations was found, as well as a positive order with respect to the partial pressure of H₂, and a slightly negative order with respect to phosphite concentration and CO partial pressure.     

Non-heme iron catalysts for the benzylic oxidation: a parallel ligand screening approach

Ethylbenzene and 4-ethylanisole were used as model substrates for benzylic oxidation with H₂O₂ or O₂ using a range of non-heme iron catalysts following a parallel ligand screening approach. Effective oxidation was found for Fe complexes based on tetra- and pentadentate nitrogen ligands affording the corresponding benzylic alcohol and ketone.