Cleavage Of Benzylic Research Articles

Collisional activation spectra of bisbenzylisoquinoline alkaloids

Collisional activation (CA) spectra of the molecular protonated ions generated under fast atom bombardment (FAB) and the molecular ions under electron ionization (EI) from 14 bisbenzylisoquinoline alkaloids have been compared. The FAB CA spectra show mainly elimination of MeOH from the MH+ ion and no characteristic fragmentation pattern. The EI spectra, on the other hand, show abundant structurally diagnostic ions free of doubly charged ions. The double benzylic cleavage results in bisisoquinoline ions giving rise to the most intense peak in the spectra of all the compounds. Loss of one of the isoquinoline moieties comprising rings C and D and elimination of both the benzyl groups (rings E and F) are characteristic of compounds containing no 1,4-dioxine bridge (1–5). These compounds are also characterized by more abundant (>50%) [M – Me]+ ions, while the compounds with a 1,4-dioxine bridge give [M – Me]+ ions with <50% abundance.

ChemInform Abstract: Chiral Building Blocks for the Synthesis of N‐Containing Natural Products. Part 1. Enantiomerically Pure Oxygenated 1‐Phenylethylamines from Substituted Acetophenones by Reductive Amination and Regiospecific Benzylic Cleavage.

AbstractThe acetophenones (I) are converted to the chiral imines (III) which are directly reduced, yielding the amines (IV).

Enantiomerically pure oxygenated 1-phenylethylamines from substituted acetophenones: By reductive amination and regiospecific benzylic cleavage

An efficient method for the asymmetric synthesis of chiral, oxygenated 1-phenyl-ethylamines ( 1) in essentially two steps is described. The substituted acetophenones 2 are reductively aminated with unsubstituted chiral 1-phenylethylamine (“PEA”, 3), via the corresponding imines 4. These can directly be hydrogenated with high diastereoselectivities to the secondary amines 5, which are obtained diastereomerically pure by simple recrystallization. The bis-benzylic amines 5 are cleaved astonishingly regioselectively by hydrogenolysis, leading to the desired primary amines 1.

Gas chromatographic and mass spectrometric characterization of isomeric alkylthiophenes (C20) and their occurrence in deep sea sediments

AbstractSix isomeric C20 alkylthiophenes were synthesized in order to prove the occurrence of such compounds in various deep sea sediments. As expected from the analogy with the corresponding saturated hydrocarbons, 2‐ and 3‐heptadecylthiophene have considerably longer relative retention times than the isomeric isoprenoid compounds, i.e. 2‐ and 3‐(4,8,12‐trimethyltridecyl)thiophene and 3‐ and 4‐methyl‐2‐(3,7,11‐trimethyldodecyl)thiophene. Covats retention indices for all compounds were determined by isothermal analysis at 190°C on two different silicone‐coated capillary columns. The mass spectra of the monoalkylated thiophenes show a base peak at m/z 98 corresponding to a Mcafferty rearrangement product in the case of the 3‐substituted isomers, whereas a simple benzylic cleavage dominates in the mass spectra of 2‐alkylthiophenes. 4‐Methyl‐2‐(3,7,11‐trimethylodecy)thiophene is an exception from this simple rule because also shows the McLafferty rearrangement as dominant fragmentation. Two of the isoprenoid thiophenes are prominent compounds in various deep sea sediments.

Identification and quantification of halogenated and non-halogenated octylphenol polyethoxylate residues by gas chromatography/mass spectrometry using electron ionization and chemical ionization

Residues of octylphenol polyethoxylates (OPEO) are frequently found in wastewater effluents. OPEO are commonly used surfactants. The polyethoxy chain of OPEO may be shortened or carboxylated during biological wastewater treatment and the aromatic ring chlorinated or brominated during wastewater disinfection with chlorine. Mass spectral data obtained using electron ionization (EI) and chemical ionization (CI) are presented which positively characterize these residues. For CI, methane was used as the reactant gas and protonated molecular ions were observed. The most prominent ions formed under EI resulted from benzylic cleavage while the prominent ions formed under CI resulted from alkyl ion displacement and olefin displacement. EI and CI mass spectra are summarized and fragmentation mechanisms are proposed. Response factors are presented for quantitative analysis by single ion monitoring.

Mass Spectrometric Investigations of Phenylacetic Acid Derivatives, III: Fragmentations of meta‐ and para‐substituted Phenylacetamides after Electron Impact

AbstractThe electron impact induced fragmentations of m‐ and p‐substituted phenylacetamides and N,N‐dimethyl‐phenylacetamides 1–14 were investigated and compared with the o‐analogues. All m‐ and p‐substituted amides yield molecular ions with high relative intensities which do not lose their meta‐ and para‐substituents. Loss of HNCO from M+˙ is dominant in the prim, amides, whilst for the tert. amides the classical benzyl cleavage is the most favourable fragmentation pathway.

Conversion of d-fructose into 4-amino, 4-amino-4- C-methyl and 3,4,5-triamino derivatives of l-sorbose

The 1,5-dialdehydes generated via periodate cleavage of benzyl β- d-fructopyranoside ( 1) and 1,2- O-isopropylidene- d-fructopyranose ( 10) undergo cyclyzation with nitromethane with high stereoselectivity, yielding 4-deoxy-4-nitrohexulopyranoses of the α- l- sorbo ( 2, 11) and α- l- tagato ( 4) configurations only, in 3:1 and 2:1 ratios, respectively. Nitroethane cyclization affords four methyl-branched 4-nitro-hexuloses with a 12:6:2:1 stereoselectivity, of which the major three have been isolated and characterized to be the α- l- sorbo ( 18), β- d- psico ( 20), and α- l- tagato ( 22) isomers. Hydrogenation of the nitro function smoothly generated, in high yields, the respective 4-amino-4-deoxyhexulopyranoses of the α- l- sorbo ( 14, 23), α- l- tagato ( 9), and β- d- psico ( 24) configurations. Subjection of the nitroacetates 2 and 11 to amination with methanolic ammonia — a double elimination-addition sequence — and, subsequently, to acetylation, furnished the 3,5-diacetamido-4-nitro-α- l-sorbopyranoses 7 and 15 in 53 and 64% yields, respectively, which were readily converted by hydrogenation into the respective 3,4,5-triamino-3,4,5-trideoxy-α- l-sorboses 6 and 16, representing the first triaminosugars of this type. Structural and configurational assignments were based on conclusive 1H-n.m.r. data, on rotational comparisons, and on stereochemical considerations, and were sustained by X-ray crystallographic analyses of benzyl 4-deoxy-4-nitro-α- l-tagatopyranoside ( 5) and its methyl-branched analog 22.

Identification of aromatic dihydroxy acids in biological fluids.

3,5-Dihydroxyphenylpropionic acid, 3,5-dihydroxycinnamic acid and 2,3-dihydroxycinnamic acid were detected for the first time to be components of human urine. In the course of this investigation all constitutional isomers of dihydroxy-benzoic, -phenylpropionic, -phenylacetic and -cinnamic acid were synthesized. Mass spectra and retention indices of methyl and trimethylsilyl (TMS) derivatives were determined. In contrast to many other substituted aromatic compounds the mass spectra of methyl and TMS derivatives of dihydroxy aromatic acids often allow a firm distinction to be made between constitutional isomers: TMS derivatives of aromatic acids containing two hydroxy groups located in the ortho position to each other can be recognized by ions resulting from a primary cleavage reaction mainly in the side chain or ester group, followed by loss of tetramethylsilane. In methyl derivatives of 1,2,3-trisubstituted isomers, methoxy groups are lost much more easily from the ions corresponding to the benzylic cleavage than in other isomers. Methyl derivatives of dihydroxycinnamic acids containing at least one methoxy group in the ortho position to the side chain are characterized by a fragmentation reaction, corresponding to the loss of dimethyl ether. TMS and methyl derivatives of 3,5-dihydroxy aromatic acids show unique structure-specific fragmentation reactions.

The mass spectra of some benzyl esters and thioethers

AbstractThe electron impact mass spectra of a large number of benzyl esters of carboxylic acids are reported. The fragmentation behaviour is discussed and the esters are divided into groups according to structure and fragmentation. For most esters benzylic cleavage with H transfer competes with simple cleavage.

Polyhalogenoaromatic compounds. Part 50. Reactions of 4-benzyloxytetrahalogenopyridines with nucleophiles

Reaction of 4-benzyloxy-3,5-dichloro-2,6-difluoro-(1; R = CH2Ph) and 4-benzyloxytetrachloropyridine (2; R = CH2Ph) with various nucleophiles (N,N-dimethylhydrazine, piperidine, N,N,N′,N′-tetramethylethane-1,2-diamine, triphenylphosphine) occurs unexpectedly at the benzylic methylene group with alkyl–oxygen cleavage to give the corresponding benzylammonium (4) or triphenylphosphonium salt (9) respectively. The molecular structure of the salt derived from 4-benzyloxytetrachloropyridine and N,N-dimethylhydrazine was confirmed by an X-ray study. Preliminary experiments of utilising the benzyl cleavage for the preparation of various benyzl derivatives (PhCH2X;X = CI, Br, I, CN, N3) are described.

Formation and structure of [C8H8O]+˙ ions, generated from gas phase ions of phenyl‐cyclopropylcarbinol and 1‐phenyl‐1‐(hydroxymethyl)cyclopropane

AbstractThe structure and formation of [C8H8O]+. ions generated from phenylcyclopropylcarbinol and 1‐phenyl‐1‐hydroxymethylcyclopropane upon electron impact, have been studied using kinetic energy release measurements, by determination of ionization and appearance energies and by collisional activation. It is shown that the non‐decomposing [C8H8O]+˙ ions have exclusively the structure of the enol ion of phenylacetaldehyde, although it is less stable than the enol ion of acetophenone by about 45 kJ mol−1. This has been interpreted as an indication that the [C8H8O]+˙ ions from phenylcyclopropylcarbinol are formed by an attack of either the phenyl ring or the hydroxyl group upon the C‐1C‐2 (or C‐1C‐3) bond of the cyclopropane ring under a simultaneous expulsion of ethene and migration of the attacking group to the C‐1 position. The [C8H8O]+˙ ion from 1‐phenyl‐1‐(hydroxymethyl)cyclopropane is formed by opening of the cyclopropane ring via a benzylic cleavage. A kinetically controlled hydrogen shift in the resulting ring opened ion prior to or during ethene loss then leads to the formation of [C8H8O]+˙ ions which have the structure of the enol ion of phenylacetaldehyde.

Zur Biotransformation von Zipeprol (Mirsol ® ) beim Menschen: Gaschromatographisch/massenspektrometrische Untersuchungen mit Ammoniak als selektivem Reaktandgas

After oral application of Zipeprol (Mirsol) the unchanged drug and nine degradation products were detected in human urine; six of them could be identified. All identified metabolites were detected in the alkaline urine fraction; after acid hydrolysis N-(2-hydroxyethyl)-piperazine was found as an artifact. With respect to the presented results, biotransformation of Zipeprol in man mainly follows three degradation routes: 1. alpha-cleavage leading to metabolite M4; 2. cleavage of the exocyclic N-C-bond of the piperazine ring leading to metabolites M3, M5, M6; 3. benzylic cleavage leading to benzylalcohol (M1); oxidation leading to 2-hydroxy-2-phenylacetic acid (mandelic acid, M2).

Benzyl cleavage in the oxidation of cycleanine by mercuric acetate

The dehydrogenation of cycleanine with mercuric acetate in 10% AcOH (at the boil) has been studied. It has been shown that it is accompanied by oxidative cleavage similar to benzyl cleavage under the action of electron impact. The main reaction product (without complexone) is the 8-(4-hydroxymethylphenoxy)-6,7-dimethoxy-2-methylisoquinolinium salt C19H20NO4Cl·1.5H2O, mp 196°C. The oxidation of cycleanine in the presence of ethylenediaminetetraacetic acid gave the mercuride C19H19NO3I2Hg·2H2O, mp 240°C (water).

Hydrogen rearrangement in molecular ions of alkyl benzenes: Appearance potentials and substituent effects on the formation of [C7H8]+ ions

AbstractThe mechanism of the formation of [C7H8]+ ions by hydrogen rearrangement in the molecular ions of 1‐phenylpropane and 1,3‐diphenylpropane has been investigated by looking at the effects of CH3O and CF3 substituents in the meta and para positions on the relative abundances of the corresponding ions and on the appearance energies. The formation of [C7H8]+ ions from 1,3‐diphenylpropane is much enhanced at the expense of the formation of [C7H7]+ ions by benzylic cleavage, due to the localized activation of the migrating hydrogen atom by the γ phenyl group. A methoxy substituent in the 1,3‐diphenylpropane, exerts a site‐specific influence on the hydrogen rearrangement, which is much more distinct than in 1‐phenylpropane and related 1‐phenylalkanes, the rearrangement reaction being favoured by a meta methoxy group. The mass spectrum of 1‐(3‐methoxyphenyl)‐3‐(4‐trideuteromethoxyphenyl)‐propane shows that this effect is even stronger than the effect of para methoxy groups on the benzylic cleavage. From measurements of appearance potentials it is concluded that the substituent effect is not due to a stabilization of the [C7H7X]+ product ions. Whereas the [C7H7]+ ions are formed directly from molecular ions of 1‐phenylpropane and 1,3‐diphenylpropane, the [C7H8]+ ions arise by a two‐step mechanism in which the s̀ complex type ion intermediate can either return to the molecular ion or fragment to [C7H8]+ by allylic bond cleavage. Obviously the formation of this s̀ complex type ion, is influenced by electron donating substituents in specific positions at the phenyl group. This is borne out by a calculation of the ΔHf values of the various species by thermochemical data. Thus, the relative abundances of the fragment ions are determined by an isomerization equilibrium of the molecular ions, preceding the fragmentation reaction.

Peptidsynthese: Verfolgung der Abspaltung von Benzylschutzgruppen mittels 1H‐NMR.‐Spektroskopie

Peptide synthesis: The following of the cleavage of benzyl protecting groups with 1H‐NMR. spectroscopy.In spite of the great number of signals 1H‐NMR. spectroscopy can be used to demonstrate the presence or absence of oxygen bound benzyl groups in protected viz. deprotected peptides.

The question of the intemediacy of carbanions in base-catalyzed cleavage of benzyl &.sbnd; silicon, benzyl  tin, and aryl  tin bonds

The question of the intemediacy of carbanions in base-catalyzed cleavage of benzyl &.sbnd; silicon, benzyl  tin, and aryl  tin bonds

Syntheses of oxazolecarboxylic acid derivatives. VII. Hydrogenolysis of aminoxazoles. (1)

In order to examine the reductive cleavage of aminoxazoles, benzyl 5-phenyl-2-oxazolecarbamate (I), 2-amino-5-phenyloxazole (II), and few related compounds were submitted to catalytic reduction at ordinary pressure, using various catalysts, and following observations were made. 1) I is converted to phenethylurea (IV) via II when using palladium-carbon catalyst in ethanol, and via 1-carbobenzyloxy-3-phenethylurea (VI) when using platinum oxide catalyst. However, II is obtained selectively when using palladium-barium sulfate catalyst in ethanol, and VI, when using platinum oxide catalyst in acetic acid. 2) II affords IV when using either palladium-carbon or platinum oxide catalyst in ethanol or acetic acid. 3) Hydrochloric acid promotes ring cleavage but alkali markedly inhibits fission. 4) Raney nickel is inactive as a catalyst in this reaction. 5) Ring cleavage of ethyl 5-phenyl-2-oxazolecarboxylate (IX) and 5-phenyloxazole (X) do not progress under these conditions.

Cleavage of Benzyl-, Diphenylmethyl- and Triphenylmethyltrimethylsilanes by Potassium Amide and Certain Other Bases1

Cleavage of Benzyl-, Diphenylmethyl- and Triphenylmethyltrimethylsilanes by Potassium Amide and Certain Other Bases¹