Cleavage Of Benzylic Research Articles

Antineoplastic agents. 443. Synthesis of the cancer cell growth inhibitor hydroxyphenstatin and its sodium diphosphate prodrug.

A structure-activity relationship (SAR) study of the South African willow tree (Combretum caffrum) antineoplastic constituent combretastatin A-4 (3b) led to the discovery of a potent cancer cell growth inhibitor designated phenstatin (5a). This benzophenone derivative of combretastatin A-4 showed remarkable antineoplastic activity, and the benzophenone derivative of combretastatin A-1 was therefore synthesized. The benzophenone, designated hydroxyphenstatin (6a), was synthesized by coupling of a protected bromobenzene and a benzaldehyde to give the benzhydrol with subsequent oxidation to the ketone. Hydroxyphenstatin was converted to the sodium phosphate prodrug (6e) by a dibenzyl phosphite phosphorylation and subsequent benzyl cleavage (6a --> 6d --> 6e). While hydroxyphenstatin (6a) was a potent inhibitor of tubulin polymerization with activity comparable to that of combretastatin A-1 (3a), the phosphorylated derivative (6e) was inactive.

Benzylic cleavage and McLafferty rearrangement under electron ionization conditions in the fragmentation of 5,6-dialkyl-2, 4-diarylpyrimidines

Several 5,6-dialkyl-2,4-diarylpyrimidines were prepared and their electron ionization (EI) mass spectra reported. The benzylic cleavage takes place easily together with an important McLafferty rearrangement. The involvement of the nitrogen atom appears to be important in the fragmentation of 5-methyl-substituted pyrimidines. In contrast, the 6-methyl-substituted pyrimidines undergo benzylic cleavage without hydrogen transfer. Thus, the difference in the mass spectrometric behaviour allows the identification of these isomeric compounds which, in contrast, exhibit only small differences in their NMR spectra. Copyright 1999 John Wiley & Sons, Ltd.

Studies in organic mass spectrometry; Part 26. Unimolecular decomposition of ortho-methoxy-substituted diphenylmethyl cations

A double rearrangement (hydrogen migration followed by carbon–carbon displacement) constitutes the main fragmentation process of the 2-methoxydiphenylmethyl cations formed by benzylic cleavage of the molecular ion of ortho-methoxy-substituted 1,1diphenylalkanes with a wide range of internal energy. This has been demonstrated by recording mass analysed ion kinetic energy (MIKE) spectra, calculation of approximate activation energies (obtained by appearance energy difference) and calculation of a degrees-of-freedom effect. A geometry of the transition state, which accounts for the observed substituent effects, is proposed .

Synthesis of phosphopeptides via global phosphorylation on the solid phase: Resolution of H-phosphonate formation

The formation of the H-phosphonate by-products from the ‘global’ phosphorylation of a Thr-containing peptide resin using both di-t-butyl and dibenzylN,N-diethylphosphoramidite was identified to result from 1H-tetrazolemediated cleavage of thet-butyl or benzyl from the intermediate dialkyl phosphite triester and re-arrangement of the resultant hydroxy phosphite diester to the H-phosphonate form. This side reaction was rectified by the use of aqueous iodine for the oxidation step in which the H-phosphonate is oxidised to the benzyl phosphorodiester which, on acidolytic treatment, gives the desired dihydrogen phosphate.

Electron-impact-induced fragmentation of long-lived C 14H 14·+ ions from dibenzyl sulphone and 1,2-diphenylethane

Gaseous dibenzyl sulphone radical cations ( 1 ·+) expel SO 2, forming C 14H 14 ·+ ions, whose fragmentation is identical with that of the radical cations of 1,2-diphenylethane ( 2 ·+). Metastable ions [ 1 − SO 2] ·+ and 2 ·+ eliminate predominantly benzene to give C 8H 8 ·+, in competition with the well-known benzyl cleavage. The [M − SO 2] ·+ ions from deuterium-labelled isotopomers of 1 react in exactly the same way as 2 ·+ ions bearing the label in corresponding positions (e.g. C 6H 5CD 2SO 2CD 2C 6H 5 ·+ and C 6H 5CD 2CD 2C 6H 5 ·+). Benzene loss is initiated by migration of a benzylic H atom, but does not occur by simple 1,2-elimination; rather, the C 6H 6 molecule incorporates an H atom from the other ring. Both fragmentation reactions are preceded by slow interannular hydrogen exchange, which involves preferentially the ortho positions of the rings; however, this exchange is coupled with a relatively fast intra-annular hydrogen ring-walk by which the hydrogens at the meta and para positions of the rings participate in the interannular exchange. The data suggest that the extrusion of SO 2 from ionized dibenzyl sulphone generates a complex of a benzyl cation and a benzyl radical, which recombine by bond formation between the benzylic α carbon atoms, but possibly also by electrophilic attack of C 6H 5CH 2 + at the various sites of C 6H 5CH 2 ·.

Unexpected Products in the Lialh4/Alcl3-Reduction of 3-O-Substituted and N-Benzyloxycarbonyl-Protected 4,6-O-[2-Methoxybenzylidene]-α-D-Glucosamine Derivatives

The reductive cleavage of benzyl 2-benzyloxycarbonylamino-2-deoxy-4,6-O-(2-methoxybenzylidene)-α-D-glucopyranoside 2 with LiAlH4-AlCl3 gave the corresponding 4-O-(2-methoxybenzyl) ether along with the 6-O-ether as expected. When, however, the 3-hydroxyl group was substituted, acetal cleavage was not the main reaction path. With a 3-O-allyl or a 3-O-methyl group, the unsymmetrical urea derivatives 8 resulted together with the formamido and N-methylamino derivatives 9 and 10, respectively, and no acetal cleavage was observed. Substitution at O-3 with a benzyl group allowed the formation of a small amount of 4-O-ether along with the formamido and N-methylamino derivatives with intact 2-methoxybenzylidene group. 1. Summer student 1996 from the Institut Universitaire Professionalisé Orléans, France. 2. Summer student 1995 from the Institut Universitaire Professionalisé Orléans, France.

Mediator-assisted selective oxidation of lignin model compounds by laccase from Botrytis cinerea

Laccase from Botrytis cinereacatalyzes benzylic oxidations and cleavage of lignin-related diphenylmethanes. Selective reactions with non-phenolic monomeric or b-1-dimeric model compounds using O 2 and redox mediators can also be carried out. At substrate to mediator ratios of 5:1, 1-hydoxybenzotriazole (HOBT) is 8-20 fold more effective than 2,2-azinobis-3-ethylthiazoline-6-sulfonate (ABTS) for such biotransformations. With unblocked phenols, ring couplings are the dominant endproducts either with or without mediators.

Sequential methyl elimination from ionized dimethyl[2.n]paracyclophane-enes (n = 3, 4, 5, 6): interaction of ionized aromatic rings in strained cyclophane conformations?

The fragmentations of the molecular ions of a series of dimethyl[2.n]paracyclophane-enes (n = 3, 4, 5, 6) have been studied by mass-analyzed ion kinetic energy (MIKE) spectrometry and deuterium labeling, The characteristic fragmentation sequence of the molecular ions of all dimethyl[2.n]paracyclophane-enes is the sequential elimination of three methyl radicals, The first methyl radical originates predominantly from the methyl substituent of the ethylene bridge and this process is accompanied by a large kinetic energy release (KER) indicative of a preceding rearrangement, The kinetic energy release distribution (KERD) observed is independent of the size of the polymethylene bridge of the dimethyl[2.n]paracyclophane-enes and even of the source of the methyl radical, Abundant loss of a second methyl radical is observed from metastable [M - CH3](+) ions in spite of a violation of the ''even-electron-rule''. Again, the methyl radical lost is chiefly a methyl substituent at the ethylene bridge, although methyl loss from the inner methylene groups of the polymethylene bridge occurs also, A small KER is observed for this fragmentation, which is again independent of the source of the methyl radical, These observations are rationalized by a rearrangement of the molecular ions by bond formation between the aromatic rings and subsequent hydrogen migrations either before or after a benzylic cleavage of the saturated bridge.

Diels-Alder reactions of diaryl thioketones with dienophiles

Thiobenzophenone and its 4,4′-dicholro derivative combine as dienes (C  S + aromatic CC bond) with dimethyl acetylenedicarboxylate, methyl propiolate, dicyanoacetylene, and cyclooctyne furnishing 1 H-2-benzothiophyrans 10, 11, 13, 14; the primary [4 + 2] cycloaddition is followed by 1,3-prototropy. In the case of the strained ( E)-cyclooctene as a dienophile, the initial nonaromatic cycloadducts 19 were isolated and rearomatized by base catalysis. - In the MS of the 1 H-2-benzothiopyrans, M + and [M + - are preeminent, both as a results of benzylic cleavage. R  H, Cl; R 1CCR 1 = dimethyl acetylenedicarboxylate, dicyanoacetylene, cyclooctyne. With trans-cyclooctene as a dienophile, the initial nonaromatic adduct is isolable.

Deprotection of Benzyl and t-Butyl Phosphate, Phosphite, and Sulfite Esters by Silica Chloride

Deprotection of phosphate, phosphate, and sulfite esters by silica chloride is described. Silica chloride is a mild, selective, and effective reagent for cleavage of benzyl and t-butyl esters of the above compounds.

A new general fragmentation reaction in mass spectrometry: The hydrogen-carbon, carbon-carbon double rearrangement of 2 heteroalkyl substituted diphenylmethyl cations

Diphenylmethyl cations formed by benzylic cleavage of the molecular ions of ortho heteroalkyl substituted 1,1-diphenylalkanes undergo the double rearrangement process (H to C followed by C to C) previously reported for ortho-methoxy derivatives. Hence the formation of substituted benzyl (or tropylium) ions allowing this double rearrangement process constitutes an interesting type of fragmentation reaction characteristic for 1,1-diphenylalkanes bearing ortho substituents (OMe, OEt, OiPr, SMe, NHMe, NMe2) which are able to transfer a hydride to the charged benzyl carbon of diphenylmethyl cations formed by benzylic cleavage of the molecular ion.

Side‐chain effects on the fragmentation behaviour of alkylthiophenes

AbstractThe processes leading to the fragment ions formed from alkylthiophene molecule ions by benzylic cleavage without and with transfer of one hydrogen from the side‐chain to the ring and the influence of additional methyl groups on the relative importance of these two fragmentation reactions were investigated.

ChemInform Abstract: Red‐Al Promoted Intramolecular Reductive Cleavage of Benzyl 4‐Hydroxy‐ 2‐butenyl Ether Structures. A Concise Preparation of Polyol Chiral Building Blocks.

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.

Removal of the Pyrrolidine Substituent by Dehydrogenation of 4‐Pyrrolidin‐2‐yl‐3,4‐dihydro‐and 1,2,3,4‐tetrahydroisoquinolines

AbstractPyrrolidin‐2‐yl‐groups located at C‐4 of 3,4‐dihydro‐ or 1,2,3,4‐tetrahydroisoquinolines, respectively, are lost in the course of dehydrogenation of these isoquinoline derivatives. However, acyclically substituted isoquinolines, hydrogenated in ring B, 2‐benzyl‐4‐(l‐dimethylaminoethyl)‐1,2,3,4‐tetrahydroisoquinoline, e.g., show loss of the amine group only by benzylic cleavage, affording 4‐ethylisoquinoline. Scope and limitation of this reaction are determined using specifically substituted isoquinolines.

Election Impact Mass Spectra of para-Substituted N-Heteroaryl Benzylamines

The 70 eV electron impact mass spectra of some para-substituted N-heteroaryl benzylamines, synthesized through the corresponding Schiff bases, are reported. Typical fragmentation patterns are discussed with the aid of mass analyzed ion kinetic energy spectra and exact mass measurements. The compounds are relatively stable under electron impact, the molecular ion being the base peak or the second most intense ion in the spectra. The dominating breakdown process is the benzylic cleavage, that gives rise to the base peak in some of the investigated compounds and to the second intense peak in others

Red-Al promoted intramolecular reductive cleavage of benzyl 4-hydroxy-2-butenyl ether structures. A concise preparation of polyol chiral building blocks

A new concise and practical method for the preparation of polyol chiral building blocks has been developed based on the finding of unprecedented Red-Al promoted intramolecular reductive cleavage of benzyl 4-hydroxy-2-butenyl ether structures and the synthetic utility has been demonstrated by accomplishment of an expeditious synthesis of the compactin lactone derivative.

Hydrogen‐carbon, carbon‐carbon double rearrangement induced by proximity effects. 1–formation of methoxybenzyl ions in the electron impact mass spectra of substituted 1,1‐bis(dimethoxyphenyl)methanes

AbstractThe 75 eV electron impact mass spectra of 1,1‐bis(dimethoxyphenyl)methanes bearing o‐methoxy groups are dominated by intense peaks corresponding, at least formally, to benzyl ions [(CH3O)2C6H3CH2]+ (b). They arise from ions [((CH3O)2C6H3)2CH]+ (a), which are in turn formed from molecular ions by loss of an alkyl radical through benzylic cleavage. The analysis of compounds labelled with 2H or 13C at methoxy groups led to the determination of the mechanism. Hydrogen migration, as hydride, followed by electrophilic substitution by the methylene carbon of the phenyl methylene ether cation through a six‐centred transition state is responsible for the formation of benzylic ions b.

Pd/charcoal-catalysed cleavage of benzyl ester protecting groups in poly(benzyl acrylate) and poly(benzyl methacrylate)

The cleavage of benzyl protecting groups of poly(benzyl acrylate), poly(benzyl malolactonate) and poly(benzyl methacrylate) by Pd/charcoal-catalysed hydrogenolysis was investigated in order to show the consequences of chemical modification on the molecular structures of the resulting polymeric compounds. It is shown that such catalytic cleavage is a general reaction that depends very much on the structure of the porous charcoal and on the location of the Pd-metal catalyst, which can be either at the surface or well inside the pores, or both. The rate of cleavage depends on many factors, namely nature of the parent polyacid backbone, stirring rate, solvent, relative amounts of poly(benzyl ester) and of catalytic system, etc. However, molecular weights, molecular-weight distribution and the origin of the catalytic system seem to be the main factors. Data confirm that partial catalytic hydrogenolysis can lead to the formation of blocky acid/ester copolymers or to mixtures of homopolymers depending on the structure of the Pd/charcoal catalytic system.

Contrasting chemical and physical properties of [o‐ and [p‐(N,N‐dimethylamino) phenyl]phosphines and phosphonium salts

AbstractThe rate of alkylation of (2‐N,N‐dimethylaminophenyl)diphenylphosphine with benzyl bromide in chloroform is faster than that of the corresponding reaction of (4‐N,N‐dimethylaminophenyl)diphenylphosphine. This result is discussed in terms of a through‐space N2p–P(IV) interaction for the former.The rate of alkaline cleavage of benzyl(4‐N,N‐dimethylaminophenyl)diphenylphosphonium bromide, which gives toluene, is slower than the rate of alkaline cleavage of benzyl(2‐N,N‐dimethylaminophenyl)diphenylphosphonium bromide, which gives dimethylaniline. This result is also discussed in terms of the through‐space N2p–P(IV) interaction.The 31P NMR spectra of a series of ortho‐dimethylamino‐substituted triarylphosphines and benzyltriarylphosphonium halides show that the phosphorus atom is more shielded than in the corresponding para‐dimethylamino compounds, as anticipated on the basis of an N2p–P(IV) interaction for the former.

Reduction with Metal Borohydride-Transition Metal Salt System. II. Reduction of Benzyl Acetates to Hydrocarbons with Sodium Borohydride-Nickel(II) Chloride

Abstract Reductive cleavage of benzyl acetates selectively with nickel boride yielding corresponding hydrocarbons is described.