Pyrrolopyrimidine nucleosides VII. A study on electrophilic and nucleophilic substitution at position six of certain pyrrolo[2,3-d] pyrimidine nucleosides

A study involving the reactivity of the pyrrolo[2,3-d] pyrimidine ring system at position 6 with another exocyclic group (CN or -NH₂) already residing at C5 has established that hydrogen and bromine are susceptible to electrophilic and acid-catalyzed nucleophilic substitution, respect-tively. In one instance a strong nucleophile (hydrazine) gave nucleophilic substitution at position 6 which was followed by a reaction with the o-nitrile group to afford the tricyclic nucleoside 4,5-diamino-8-(β-D-ribofuranosyl)pyrazolo[3′, 4′ :5,4] pyrrolo[2,3-d] pyrimidine (4).     

Formation and reactions of metal-metal bonded heterobimetallic (C5H4PR2)-bridged (Zr-Ir) and (Zr-Rh) complexes: evidence for the participation of metal hydride intermediates

Treatment of the complexes [(C(5)H(4)PR(2))(2)Zr(CH(3))(2)](b: R = isopropyl; c: R = cyclohexyl) with the reagent HIr(CO)(PPh(3))(3) (2b) yield the heterobimetallic complexes [mu-C(5)H(4)PR(2))(2)(H(3)C-Zr-Ir(CO)(PPh(3)))] (4b, 4c) with evolution of methane. The reaction of the -PPh(2) substituted analogue with initially yields an intermediate [(H(3)C)(2)Zr(mu-C(5)H(4)PPh(2))(2)Ir(H)(CO)(PPh(3))] 5a, that still contains both methyl groups at zirconium and does not contain a metal-metal bond. At room temperature, the intermediate reacts further with methane formation to eventually yield the (Zr-Ir) complex 4a. The corresponding [mu-C(5)H(4)PR(2))(2)(H(3)C-Zr-Rh(CO)(PPh(3)))] complexes 3a (R = Ph) and 3b (R = isopropyl) react cleanly with isopropyl alcohol to liberate methane and yield the corresponding [mu-C(5)H(4)PR(2))(2)(Me(2)CHO-Zr-Rh(CO)(PPh(3)))] products (7a, 7b). Carefully monitoring the reaction of with Me(2)CHOH by NMR revealed that the Zr-Rh functionality is attacked first to give the intermediate [Me(Me(2)CHO)Zr([micro sign]-C(5)H(4)PR(2))(2)Rh(H)(CO)(PPh(3))] (6b). This intermediate then reacts further to cleave off methane and re-form the (Zr-Rh) metal-metal bond to yield the product 7b. The tetrametallic mu-oxo-(Zr-Rh) metallocene derivate 11a was obtained starting from the (Zr-Rh) complex 3a and it was characterized by X-ray diffraction. It may be that this reaction is also initiated by H-OH addition to the [Zr-Rh] metal-metal bond.     

Dioxygenyl salts containing doubly charged mononuclear counterions

Evidence is presented for the existence of (O₂⁺)₂MF₆^2?(M=Ni,Mn) salts. These salts are marginally stable up to about 10°C and are characterized by an OO stretching frequency of about 1805 cm^?1.     

Stereoselective Syntheses of Benz[f]isoindoline-Derivatives by Intramolecular Cycloadditions of Styrenes to Olefins

The N-allyl-N-cinnamyl amide 10 undergoes thermal cyclization to a 2:1-mixture of the trans- and cis-benz(f)isoindolines 11a and 12a . By comparison, the thermolysis of the corresponding bis-cinnamylamide 14 proceeds in a highly stereoselective manner to give the cis-fused[4+2]-adduct 16a . Similarly, the trans-fused stereoisomeric adducts 30a and 31a were obtained with high stereochemical control on heating the N-allyl-N-diphenylallyl amide 28 . The thermal transformations 4 → 5 + 6a and 17 → 18a + 20a show the competitive formation of [2+2]-adducts. An alternative approach to (substituted) benz[f]isoindolines 16 via the all-cis-isomer 24a has been developed. The described structures have been assigned on the basis of spectral evidence, chemical correlations and by X-ray-diffraction study of the isomer 16b . These results illustrate the utility of substituent interactions in order to direct intramolecular cyclo-additions at will towards either endo- or exo-products.     

A molecular-dynamics study of a model S(N)1 dissociation reaction at the water liquid/vapor interface

The thermodynamics and dynamics of a model S(N)1 reaction: t-BuCl --> t-Bu+ + Cl- is studied at the water liquid/vapor interface using molecular-dynamics computer simulations. The empirical valence bond approach is used to couple two diabatic states, covalent and ionic, in the electronically adiabatic limit. Umbrella sampling calculations are used to calculate the potential of mean force along the reaction coordinate (defined as the t-Bu to Cl distance) in bulk water and in several locations at the interface. We find a significant increase of the dissociation barrier height and of the reaction free energy at the interface relative to the bulk. This is shown to be due to the reduced polarity of the interface. Reactive flux correlation function calculations show significant deviation of the rate constant from the transition-state theory: The transmission coefficients range from 0.49 in the bulk to 0.05 above the Gibbs surface. The low transmission coefficient at the interface despite the lower friction is shown to be due to slow vibrational relaxation.     

Benzylidène-5-hydroxy-4-dihydro-2,5-thiophènecarboxanilides-3-(Z): Synthèse et isomérisation en benzyl-5-hydroxy-4-thiophènecarboxanilides-3

(Z)-5-Benzylidene-2,5-dihydro-4-hydroxy-3-thiophenecarboxanilides: Synthesis and Isomerization into 5-Benzyl-4-hydroxy-3-thiophenecarboxanilides Upon treatment with an arylamine in boiling xylene, the esters I yield predominantly the corresponding anilides II, along with a small but variable amount of the isomeric thiophene derivatives III (Table 1). On the other hand, the derivatives III can be readily prepared by base- or acid-catalyzed isomerization of II . Esters I can also be isomerized to the corresponding thiophene derivatives IV (Scheme 6), but only in the presence of a strong acid (Table 4). The two series of isomers reported in Tables 2 and 3 present spectral differences which allow unambiguous structural assignments. The (Z)-configuration for compounds of Table 2 is confirmed by a NOE study carried out on the O-methyl derivatives 6a and 7a .     

New designer drug 1-(3-trifluoromethylphenyl) piperazine (TFMPP): gas chromatography/mass spectrometry and liquid chromatography/mass spectrometry studies on its phase I and II metabolism and on its toxicological detection in rat urine

Studies are described on the phase I and II metabolism and the toxicological analysis of the piperazine-derived designer drug 1-(3-trifluoromethylphenyl)piperazine (TFMPP) in rat urine using gas chromatography/mass spectrometry (GC/MS) and liquid chromatography/mass spectrometry (LC/MS). The identified metabolites indicated that TFMPP was extensively metabolized, mainly by hydroxylation of the aromatic ring and by degradation of the piperazine moiety to N-(3-trifluoromethylphenyl)ethylenediamine, N-(hydroxy-3-trifluoromethylphenyl)ethylenediamine, 3-trifluoromethylaniline, and hydroxy-3-trifluoromethylaniline. Phase II reactions included glucuronidation, sulfatation and acetylation of phase I metabolites. The authors' systematic toxicological analysis (STA) procedure using full-scan GC/MS after acid hydrolysis, liquid-liquid extraction and microwave-assisted acetylation allowed the detection of TFMPP and its above-mentioned metabolites in rat urine after single administration of a dose calculated from the doses commonly taken by drug users. Assuming similar metabolism, the described STA procedure should be suitable for proof of an intake of TFMPP in human urine.     

Electron bombardment fragmentation of size selected molecular clusters

(CO₂) _n , (NO) _n and (NH₃) _n clusters are generated in a supersonic molecular beam and size selected by scattering from an He beam. By measurements of angular dependent mass spectra, TOF distributions and the angular dependence of the scattered signal quantitative information on the fragmentation probability by electron impact is derived. The van der Waals systems (CO₂) _n and (NO) _n appear only at masses which are simply multiples of the monomer mass. The preferred cluster ion is the monomer ion for all investigated cluster sizes withn=2 to 4. The fragment pattern for the quasi-hydrogen bonded (NH₃) _n -cluster shows, beside a large number of fragment masses, a preference for protonated ions. The results are explained in terms of simple models based on the structural change from the neutral to the ionized configuration and the fragmentation pattern of the monomer followed by ionmolecule reactions.