Cleavage Of Benzylic Research Articles

Selective Oxidative Cleavage of Benzyl C-N Bond under Metal-Free Electrochemical Conditions.

With the growing significance of green chemistry in organic synthesis, electrochemical oxidation has seen rapid development. Compounds undergo oxidation-reduction reactions through electron transfer at the electrode surface. This article proposes the use of electrochemical methods to achieve cleavage of the benzyl C-N bond. This method selectively oxidatively cleaves the C-N bond without the need for metal catalysts or external oxidants. Additionally, primary, secondary, and tertiary amines exhibit good adaptability under these conditions, utilizing water as the sole source of oxygen.

Palladium Mediated Selective Cleavage of Benzyl and Allyl Phosphates: A Convenient Non‐Hydrogenolytic Method for the Synthesis of Phosphates and Phospholipids.

Allyl and benzyl phosphates can be cleaved selectively using catalytic amounts of Pd/C, Pd(OH)2 and Pd(OH)2 alone, in the absence of hydrogen, respectively.This is of of immense utility during the synthesis of phospholipids and other organophosphates.

Studying the fragmentation mechanism of selected components present in crude oil by collision-induced dissociation mass spectrometry.

Structural characterization of individual compounds in very complex mixtures is difficult to achieve. One important step in structural elucidation is understanding the mass spectrometric fragmentation mechanisms of the compounds present in such mixtures. Here, different individual compounds presumed to be present in a complex crude oil mixture have been synthesized and structurally characterized by tandem mass spectrometry (MS/MS) studies. Model compounds with different aromatic cores and various substitutents were synthesized. Major effort has been put into producing isomerically pure compounds to better understand the fragmentation pattern. Each synthesized compound has been subjected to MSn studies using either a triple quadrupole or a linear ion trap mass spectrometer with electrospray or atmospheric pressure photoionization. The results are used to analyze individual compounds from a complex vacuum gas oil (VGO). The synthesized compounds and a chromatographically simplified vacuum gas oil were used for structural analysis. The major fragmentation mechanism is the benzylic cleavage of the aliphatic side chain. Each side chain can be separately removed from the aromatic core by using MSn methods. At the end of a series of fragmentations, the base aromatic core structure remains and can be chararcterized. By defining the fragmentation mechanism in complex oil samples it was possible to structurally characterize individual compounds present in a chromatographically simplified VGO. The compounds consist of an aromatic core with aliphatic side chains. Cleavage of all side chains can be achieved by MSn measurements, allowing characterization of the remaining core structure.

Silver(I)-Catalyzed Deprenylation of Allylsulfonamide Derivatives

The silver(I)-catalyzed deprenylation of sulfonamide bearing prenyl functional groups on the nitrogen atom has been developed. In this reaction, the prenyl moiety was selectively eliminated without allyl or benzyl cleavage on the nitrogen atom. In addition, geranyl was also applicable for this elimination reaction. Furthermore, sulfonamide possessing two prenyl groups underwent a double deprenylation to form the corresponding deprenylated sulfonamide. Thus, a novel reactivity between the silver cation and double bond was observed.

2-Benzylindane radical cations in the gas phase (Part I): Substituent effects on a stereoselective McLafferty reaction and related hydrogen transfer processes

In the present and the accompanying article, the unimolecular fragmentation of the radical cations of 2-benzylindane and eleven derivatives bearing meta- or para-substituents at the benzylic moiety has been studied with a special focus on the hydrogen exchange that precedes the McLafferty reaction. Standard EI mass spectra, low-energy (11eV) mass spectra and mass-analyzed ion kinetic energy (MIKE) spectra were recorded to probe the excitation-energy and ion-lifetime dependence of the fragmentation and the hydrogen exchange. Density-functional theory calculations were used to rationalize the substituent effects on the competition between the benzylic cleavage and the McLafferty reaction and to clarify the role of the distonic arenium ion-type intermediate formed by the γ-hydrogen-transfer step of the McLafferty reaction. The ipso-protonolysis of the benzyl residue giving rise to the loss of substituted benzenes specifically from most of the para-isomers was also found to reflect the hydrogen exchange.

Rapid acidolysis of benzyl group as a suitable approach for syntheses of peptides naturally produced by oxidative stress and containing 3-nitrotyrosine.

3-Nitrotyrosine (Nit) belongs to products of oxidative stress and could probably influence conformation of neurodegenerative proteins. Syntheses of peptides require availability of suitable synthon for introduction of Nit residue. Common phenolic protection groups are more acid labile, when they are attached to Nit residue. We have found that Fmoc-Nit(Bn)-OH is a good building block for syntheses of Nit containing peptides by Fmoc/tBu strategy. Interestingly, the peptides containing multiple Nit residues can be available solely by use of Fmoc-Nit(Bn)-OH synthon. Bn is removed rapidly with ca 80 % trifluoroacetic acid in dark. The cleavage of Bn from Fmoc-Nit(Bn)-OH proceeds via pseudo-first order mechanism with activation barrier 32 kcal mol(-1) and rate k = 15.3 s(-1) at 20 °C. This rate is more than 2,000,000 times faster than that for cleavage of benzyl from Tyr(Bn).

Identification of position isomers by energy-resolved mass spectrometry.

This study reports an energy-resolved mass spectrometric (ERMS) strategy for the characterization of position isomers derived from the reaction of hydroxyl radicals ((●)OH) with diphenhydramine (DPH) that are usually hard to differentiate by other methods. The isomer analogues formed by (●)OH attack on the side chain of DPH are identified with the help of a specific fragment ion peak (m/z 88) in the collision-induced dissociation (CID) spectrum of the protonated molecule. In the negative ion mode, the breakdown curves of the deprotonated molecules show an order of stability (supported by density functional theory (DFT) calculations) ortho > meta > para of the positional isomers formed by the hydroxylation of the aromatic ring. The gas phase stability of the deprotonated molecules [M - H](-) towards the benzylic cleavage depends mainly on the formation of intramolecular hydrogen bonds and of the mesomeric effect of the phenol hydroxyl. The [M - H](-) molecules of ortho and meta isomers result a peak at m/z 183 with notably different intensities because of the presence/absence of an intramolecular hydrogen bonding between the OH group and C9 protons. The ERMS approach discussed in this report might be an effective replacement for the conventional methods that requires very costly and time-consuming separation/purification methods along with the use of multi-spectroscopic methods.

Wavelength-selective cleavage of o-nitrobenzyl and polyheteroaromatic benzyl protecting groups

Evaluation of the wavelength-selective cleavage of five photolabile protecting groups from two different families has been performed. Alanine, as a model bifunctional target molecule was masked at the amino terminal with o-nitrobenzyl group and at the carboxylic terminal with benzyl-type nitrogen and oxygen polyheteroaromatics, namely acridine, (thioxo)benzocoumarin and a coumarin built on the julolidine nucleus. The photosensitivity of the corresponding alanine conjugates was studied at selected wavelengths with HPLC/UV and 1H NMR monitoring. The release of the fully deprotected molecule could be achieved by sequential irradiation in variable irradiation times, which were dependent on the heteroaromatic group used.

Highly practical iron-catalyzed C–O cleavage reactions

Facile iron-catalyzed cleavage of various allyl, cinnamyl and benzyl C–O linkages has been effected in the presence of ethylmagnesium chloride. The protocol is operationally simple (xylene–THF, r.t., 1 h), requires low catalyst loading (1 mol% FeCl2) and tolerates halides, esters, amines, ethers and olefins. The allyl moiety is converted to volatile hydrocarbons which renders laborious product separation unnecessary.

Elaboration of the ether cleaving ability and selectivity of the classical Pearlman's catalyst [Pd(OH)2/C]: concise synthesis of a precursor for a myo-inositol pyrophosphate

The cleavage of propargyl, allyl, benzyl, and PMB ethers by Pd(OH)2/C can be tuned in that order, by varying the reaction conditions. Other moieties such as C–C double bonds, esters, trityl ether, p-bromo and p-nitrobenzyl ethers are stable to these reaction conditions. Cleavage of allyl ethers can be made catalytic by using 1:1 mixture of Pd(OH)2/C and Pd/C. The synthetic potential of the selective ether cleaving ability of Pd(OH)2/C, essentially under neutral conditions, has been demonstrated by an efficient synthesis of a precursor for the preparation of an inositol pyrophosphate derivative.

O-Nucleoside, S-nucleoside, and N-nucleoside probes of lumazine synthase and riboflavin synthase.

Lumazine synthase catalyzes the penultimate step in the biosynthesis of riboflavin, while riboflavin synthase catalyzes the last step. O-Nucleoside, S-nucleoside, and N-nucleoside analogues of hypothetical lumazine biosynthetic intermediates have been synthesized in order to obtain structure and mechanism probes of these two enzymes, as well as inhibitors of potential value as antibiotics. Methods were devised for the selective cleavage of benzyl protecting groups in the presence of other easily reduced functionality by controlled hydrogenolysis over Lindlar catalyst. The deprotection reaction was performed in the presence of other reactive functionality including nitro groups, alkenes, and halogens. The target compounds were tested as inhibitors of lumazine synthase and riboflavin synthase obtained from a variety of microorganisms. In general, the S-nucleosides and N-nucleosides were more potent than the corresponding O-nucleosides as lumazine synthase and riboflavin synthase inhibitors, while the C-nucleosides were the least potent. A series of molecular dynamics simulations followed by free energy calculations using the Poisson-Boltzmann/surface area (MM-PBSA) method were carried out in order to rationalize the results of ligand binding to lumazine synthase, and the results provide insight into the dynamics of ligand binding as well as the molecular forces stabilizing the intermediates in the enzyme-catalyzed reaction.

A ‘meta effect’ in the fragmentation reactions of ionised alkyl phenols and alkyl anisoles

The competition between benzylic cleavage (simple bond fission [SBF]) and retro-ene rearrangement (RER) from ionised ortho, meta and para RC(6) H(4) OH and RC(6) H(4) OCH(3) (R = n-C(3) H(7) , n-C(4) H(9) , n-C(5) H(11) , n-C(7) H(15) , n-C(9) H(19) , n-C(15) H(31) ) is examined. It is observed that the SBF/RER ratio is significantly influenced by the position of the substituent on the aromatic ring. As a rule, phenols and anisoles substituted by an alkyl group in meta position lead to more abundant methylene-2,4-cyclohexadiene cations (RER fragmentation) than their ortho and para homologues. This 'meta effect' is explained on the basis of energetic and kinetic of the two reaction channels. Quantum chemistry computations have been used to provide estimate of the thermochemistry associated with these two fragmentation routes. G3B3 calculation shows that a hydroxy or a methoxy group in the meta position destabilises the SBF and stabilises the RER product ions. Modelling of the SBF/RER intensities ratio has been performed assuming two single reaction rates for both fragmentation processes and computing them within the statistical RRKM formalism in the case of ortho, meta and para butyl phenols. It is clearly demonstrated that, combining thermochemistry and kinetics, the inequality (SBF/RER)(meta) < (SBF/RER)(ortho) < (SBF/RER)(para) holds for the butyl phenols series. It is expected that the 'meta effect' described in this study enables unequivocal identification of meta isomers from ortho and para isomers not only of alkyl phenols and alkyl anisoles but also in other alkyl benzene series.

Characterization of phenolic compounds in the fruits of Forsythia suspensa by high‐performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry

Phenolic compounds are the major bioactive constituents of Forsythia suspensa, an important Chinese herbal medicine used for the treatment of various infectious diseases. Fragmentation behaviors of the phenolic compounds in F. suspensa were investigated by using a high-performance liquid chromatography/tandem mass spectrometry (HPLC/MS(n)) method. For common phenylethanoid glycosides, the loss of the caffeoyl moiety was the first fragmentation step, then sequential losses of rhamnose, hexose and water were observed in further fragmentations. If a substituent group presented in the beta position, the fragmentation was triggered by initial loss of a substituent group to form structures such as suspensaside A. Then it underwent the common fragmentation pathways as mentioned above, or eliminated characteristic residues of masses 134 or 152 Da, respectively. The latter pathway is reported here for the first time. The fragmentation behaviors of furofuran lignans displayed a typical cleavage of the tetrahydrofuran ring. However, the presence of a hydroxyl group at C-1 led to the successive loss of 30 Da. Neutral loss of CO(2) and benzyl cleavage were characteristic for lignans with a 2,3-dibenzylbutyrolactone skeleton. A neutral loss of 30 Da was also observed in the fragmentation pattern of flavonols. These fragmentation rules were implemented to analyze phenolic compounds in the fruits of F. suspensa. A total of 51 compounds, including 24 phenylethanoid glycosides, 21 lignans and 6 flavonols, were identified or tentatively characterized based on their retention times, UV spectra and MS fragmentation patterns.

Benzyl ions from 1,1‐(2,2′‐dimethoxyphenyl)‐substituted 2‐methylpropanes under electron ionization

The electron ionization (EI)-induced fragmentations of a series of 1,1-(2,2'-dimethoxyphenyl)-substituted 2-methylpropanes (1-20) in both 70 eV and mass-analyzed ion kinetic energy (MIKE) spectra have been investigated. The EI-MS spectra of these compounds are characterized by the presence of abundant benzyl ions. These ions result from competitive hydrogen migration from the 2- and 2'-methoxy groups on the carbenium center of the diphenylmethyl cations formed by benzylic cleavage of the molecular ions. The relative abundances of the benzyl ions arising from such competitive processes are discussed and rationalized. The steric effect of the 3- or 3'-substituents is the main discriminating factor between the two competitive processes. The structural information, arising either from the 70 eV or the MIKE spectra, is discussed.

Selective Oxidative Cleavage of Benzylic and Allylic Oximes to Their Carbonyl Compounds with Strontium Manganate in the Presence of Aluminum Chloride in Solution and under Solvent‐Free Conditions.

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Selective Oxidative Cleavage of Benzylic and Allylic Oximes to Their Carbonyl Compounds with Strontium Manganate in the Presence of Aluminium Chloride in Solution and under Solvent-Free Conditions

However,some of these methods suffer from disadvantages such aslong reaction times, low yields of the products and tediouswork up. Also many of the reports either do not describe thedoeximon oi at do al f ximes o girveow y l dsel ofali de hyd orsen o i t a d i x o e iv ect l e S . zed i d i ox er e ov s ar e d y h e d ald te a r e b i l e thof benzylic and allylic oximes in the presence of aliphaticoximes and other derivatives such as semicarbazones,phenylhydrazones and 2,4-dinitrophenylhydrazones is ofpractical importance and only a few reports are available inthe literature for this purpose.

Dicarboxylic degradation products of nonylphenol polyethoxylates: synthesis and identification by gas chromatography–mass spectrometry using electron and chemical ionization modes

The synthesis, mass spectra and detectability of four selected dicarboxylic degradation products (CAPECs) of nonylphenol polyethoxylates (NPEOs) are reported. The selected isomers have an α,α-dimethyl configuration (expressed as “dm” in their abbreviation), five to eight C atoms and a carboxyl group in the alkyl chain, and a carboxymethoxy acid group (dm-CA 5–8P1ECs). The synthesis was successfully accomplished via a reaction sequence that started from anisole. After trimethylsilylation with N, O-bis(trimethylsilyl)acetamide or methylation with (trimethylsilyl)diazomethane, the derivatives of the dm-CA 5–8P1ECs were subjected to a GC–electron ionization (EI)–MS and GC–isobutane chemical ionization (CI)–MS. In EI–MS, ion peaks at m/ z = 265 and 207, corresponding to the α,α-dimethyl structures via the benzyl cleavage of carboxyalkyl chain, were the most significant ions of the trimethylsilyl and methyl derivatives, respectively. In CI–MS, the main ion peaks of dm-CA 5-, dm-CA 6-, dm-CA 7-, and dm-CA 8P1EC after methylation were at m/ z = 129, 143, 157, and 171, respectively, corresponding to the loss of methyl phenoxyacetate from [ M + H] +; meanwhile significant peaks were detected at 321, 335, 349, and 363, corresponding to the loss of the trimethylsilanol after trimethylsilylation. The potential for the identification and quantification of individual branched carboxyalkyl isomeric mixtures of CA 5-, CA 6-, CA 7-, and CA 8P1EC metabolites based on corresponding dm-CA 5–8P1ECs revealed the advantage of the GC–CI–MS although the detection limits in CI were clearly higher than those in EI.

Heck-type Benzylation of Olefins with Benzyl Trifluoroacetates

Abstract A new synthetic method for 1-aryl-2-alkenes from 1-olefins by benzylation treating with benzyl trifluoroacetates using palladium-catalyst is developed on the basis of oxidative addition of benzyl carboxylates to Pd(0) complexes to give benzyl(carboxylato)palladium(II) complexes with cleavage of benzyl–oxygen bond.

Differentiation and quantification of linear alkyl benzenesulfonate isomers by liquid chromatography-ion-trap mass spectrometry

Discrimination and quantitation of the 20 positional isomers of C 10–C 13 linear alkyl benzenesulfonates (LAS s), based on the use of reversed-phase liquid chromatography-electrospray ionisation in negative ion mode ion-trap mass spectrometry, was undertaken. Discrimination was achieved by LAS MS-MS analysis into the ion trap, by monitoring specific fragment ions resulting from the benzylic cleavage of the carbon alkyl chain on both side of the LAS phenyl group. Parameters affecting the electrospray ionisation source and the ion-trap operation were optimised. Calibration curves for the different isomers were established and this permitted their quantitation by mass spectrometry for the first time. MS-MS responses were dependent on both the position of the phenyl group on the alkyl chain and the length of this alkyl chain, these responses being higher for the external isomers and the longer alkyl chain homologues. The precision, expressed as relative standard deviation ranged between 9 and 13%. Detection limits for LAS isomers were between 0.03 and 0.07 mg/l and therefore the method is sensitive enough to be applied to environmental samples.

Bis-Heteronucleophilic Michael Addition to Divinyl Sulfone: A New Efficient Access to Macrocycles

The Michael addition of bis(nitrogen or sulfur) nucleophiles to divinyl sulfone provides the corresponding macrocyclic adducts in good yields. The structures of some new macrocyclic sulfones are established by X-ray crystallographic analysis and NMR spectroscopy. The subsequent cleavage of benzyl or tosyl groups yields the unprotected macrocyclic sulfones. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)