A prototype for catalyzed amide bond cleavage: production of the [NH(3), H(2)O](*)(+) dimer from ionized formamide and its carbene isomer

The reaction of ionized formamide H(2)NCHO(*)(+) with water leads to an exclusive loss of CO from the complex. This contrasts with the unimolecular reaction of low-energy ionized formamide, which loses exclusively one hydrogen atom. The unimolecular loss of CO is not observed because it involves several H-transfers corresponding to high-energy barriers. Experimental and theoretical studies of the role of solvation by water on the fragmentation of ionized formamide leads to three different results: (i) In contrast with different systems previously studied, in which solvation plays only a role on one or two steps of a reaction, a molecule of water is efficient in the catalysis of the decarbonylation process because water catalyzes all the steps of the reaction of ionized formamide, including the final dissociation of the amide bond. (ii) The catalyzed isomerization of carbonylic radical cations into their carbene counterparts is shown to be an important step in the process. To study this step, a precise probe, characterizing the carbene structure by ion-molecule reaction, is for the first time described. (iii) Finally, decarbonylation of ionized formamide yields the [NH(3), H(2)O](*)(+) ion, which has not been generated and experimentally studied previously. By this method, the [NH(3), H(2)O](*)(+) ion is generated in abundance and with a low internal energy content, allowing one either to prepare, by ligand exchange, a series of other solvated radical cations or to generate covalent structures such as distonic ions. First results on related systems indicate that the conclusions obtained for ionized formamide are widespread.     

Organocatalyzed route to enantioenriched pipecolic esters: decarboxylation of an aminomalonate hemiester

Enantioenriched pipecolic esters were prepared in good yields in the decarboxylation, at room temperature, of N-protected piperidinohemimalonates catalyzed by cinchona alkaloids. Enantiomeric excesses as high as 72% were obtained when using 9-epi-cinchonine and the N-benzoyl substituted piperidinohemimalonate. A detailed study of the different reaction parameters revealed that the selectivity of this noncovalent organocatalyzed reaction is strongly dependent on the solvent, toluene or carbon tetrachloride being the best ones. The whole process based on the malonic acid synthesis was successfully tested on a 10 mmolar scale and established a practical alternative to the asymmetric protonation of lithium enolates.     

Synthesis of new heterocycles. 3,4-dihydropyrano[2,3,4-hi]indolizine and derivatives

Interaction of the lithium derivative of 2,3-dihydro-4H-pyrano[3,2-b]pyridine with the diethyl acetal of bromoacetaldehyde, followed by hydrolysis and subsequent ring closure afforded the novel heterocycle 3,4-dihydropyrano[2,3,4-hi]indolizine which was inacessible by the Tschitschibabin method. However, the 2-phenyl derivative was easily prepared by the Tschitschibabin method.     

Ultrastructural aspects of the acetylation of cellulose

An ultrastructural study of the acetylation of cellulose was achieved by subjecting well characterized cellulose samples fromValonia cell wall and tunicin tests to homogeneous and heterogeneous acetylation. The study involved transmission electron microscopy observations on negatively stained microcrystals as well as diffraction contrast images of the cross sections of wall fragments at various stages of the reaction. These observations showed that the acetylation of crystalline cellulose proceeds by a reduction of the diameters of the crystals while their lengths are reduced to a lower extent. These results were corroborated by electron and X-ray diffraction experiments that showed that during the reaction there was a rapid decrease in the intensities of the equatorial diffraction spots of cellulose, whereas those located on the meridian or close to the meridian stayed constant. A model of acetylation of the cellulose crystal is presented. It is based on a non swelling reaction mechanism that affects only the cellulose chains located at the crystal surface. In the case of homogeneous acetylation, the partially acetylated molecules are sucked into the acetylating medium as soon as they are sufficiently soluble. In heterogeneous conditions the cellulose acetate remains insoluble and surrounds the crystalline core of unreacted cellulose.     

Direct access to ferrocenyliminium salts and their use in synthesis

Reduction of ferrocenylketoximes by titanium trichloride provides a convenient route for the preparation of ferrocenyliminium salts, which have been shown to be useful for the synthesis of new derivatives.     

Regioselective syntheses, structural characterization, and electron ionization mass spectrometric behavior of regioisomeric 2,3-disubstituted 2-imino-1,3-thiazolidin-4-ones

The regioselective syntheses of 3-alkyl(aryl)-2-(anthracen-9'-ylimino)-1,3-thiazolidin-4-ones (2) and 2-alkyl(aryl)imino-3-(anthracen-9'-yl)-1,3-thiazolidin-4-ones (3) from N-(anthracen-9-yl)-N'-alkyl(aryl)thioureas were accomplished effectively using methyl bromoacetate and bromoacetyl bromide, respectively. Detailed structural characteristics were confirmed mainly by NMR techniques. The mass spectrometric behavior of the resulting sets of compounds of known structures was shown to be characteristic for each set. Some interesting fragmentation pathways involving the transfer and rearrangements of various moieties were also revealed, as well as regioisomerization for particular substituent-specific fragmentations.     

Identification of phenylbutyrylglutamine,a new metabolite of phenylbutyrate metabolism in humans

Phenylbutyrate is used in humans for treating inborn errors of ureagenesis, certain forms of cancer, cystic fibrosis and thalassemia. The known metabolism of phenylbutyrate leads to phenylacetylglutamine, which is excreted in urine. We have identified phenylbutyrylglutamine as a new metabolite of phenylbutyrate in human plasma and urine. We describe the synthesis of phenylbutyrylglutamine and its assay by gas chromatography/mass spectrometry as a tert-butyldimethylsilyl or methyl derivative, using standards of [(2)H(5)]phenylbutyrylglutamine and phenylpropionylglutamine. After administration of phenylbutyrate to normal humans, the cumulative urinary excretion of phenylacetate, phenylbutyrate, phenylacetylglutamine and phenylbutyrylglutamine amounts to about half of the dose of phenylbutyrate. Thus, additional metabolites of phenylbutyrate are yet to be identified.     

[2 + 2] Cycloaddition reactions of unsymmetrically substituted carbodiimides

N-Alkyl-N′-arylcarbodiimides add alkyl and aryl isocyanates to the N-alkyl substituted CN double bond to yield 4-arylimino-1,3-diazetidine-2-ones 3. In the case of bulky alkyl substituents the reaction still proceeds across the sterically hindered CN double bond. N-Aryl-N′-[(4-dimethylamino)phenyl]carbodiimides form [2 + 2] cycloadducts with aryl isocyanates preferentially across the CN double bond not attached to the electron-rich aryl groups. However, steric crowding on this CN double bond directs the reaction to the adjacent double bond of the heterocumulative system. The rate of the [2 + 2] cycloaddition reaction of N'-methyl-N′-phenylcarbodiimide with 4-nitrophenylisocyanate is about 2.5 times faster in acetonitrile than in benzene.     

Librational relaxation and IR line broadening of matrix isolated CO

The IR line profile corresponding to the fundamental vibrational transition of CO isolated in an Ar matrix has been studied as a function of the temperature. The spectrum consists of two superimposed bands, a sharp one and a broad one whose linewidths are respectively 0.45 and 2.7 cm^?1 at 10 K. The strong temperature dependence of the CO lineshape is mainly due to the large change in the intensity ratio of the two components. Such a behaviour is accounted for by relaxation of librational populations. The calculated contributions of the processes connecting the ground and first excited librational states to the IR linewidth are of the same order of magnitude as the values experimentally measured. However the experimental lineshape of the sharp component being rather gaussian than lorentzian, it is concluded that librational relaxation contributes significantly to the broadening of the infrared CO band but not exclusively.     

Benzoporphyrins and Acetylene-Substituted Porphyrins as Improved Photosensitizers in the Photodynamic Tumor Therapy with Porphyrin Platinum Conjugates

Summary.  A combination of a cisplatinum-like fragment and a porphyrin in the same molecule should not only result in the additivity of the dark toxicity of the platinum fragment and the phototoxicity of the porphyrin moiety, but also in the enrichment of the porphyrin platinum conjugates in tumor tissue, which cisplatinum alone does not show. To increase the penetration depth of the red light used in the photodynamic tumor therapy the conjugated system of the porphyrin components in porphyrin platinum conjugates had to be expanded. Sixteen new (NH₃)₂Pt derivatives of benzoporphyrins and acetylene-substituted porphyrins were synthesized, characterized, and tested with respect to their antitumor activity on the mammary carcinoma cell line MDA-MB-231. Received November 12, 2001. Accepted November 20, 2001