Porphyrins with exocyclic rings. Part 21: Influence of pyrrolic and carbocyclic ring alkyl substituents on the synthesis of porphyrins bearing six-membered exocyclic rings

A series of 5-substituted 4,5,6,7-tetrahydroindoles were prepared by reacting 4-substituted cyclohexanones with phenylhydrazones derived from esters of acetoacetic acid under Knorr-type reaction conditions. Related 6,6-dimethyltetrahydroindoles were also prepared by reacting dimedone with oximes by the Knorr pyrrole syntheses, followed by selective reduction of the remaining ketone moiety with diborane. The substituted tetrahydroindoles were regioselectively oxidized with lead tetraacetate to give the related 7-acetoxy derivatives, and these reacted with 5-unsubstituted pyrrole esters to give pyrrolyltetrahydroindoles. In one case, a bromo substituent was used to protect the β-position of the pyrrole reactant. Cleavage of the benzyl ester protective groups with hydrogen over Pd/C, which also removes the bromo-protective group, gave four dipyrrole carboxylic acids. These were condensed with a dipyrrylmethane dialdehyde using the MacDonald ‘2+2’ condensation to give substituted porphyrins with six-membered exocyclic rings. These structures are useful for comparison to porphyrin samples found in organic-rich sediments such as oil shales and petroleum. The presence of methyl substituents on the six-membered ring for the tetrahydroindole precursors slightly decreases the yields for porphyrin synthesis, and this effect is enhanced when the system becomes more sterically crowded due to the presence of an ethyl group of the adjacent pyrrole ring. 5-Alkyl substituted tetrahydroindoles were also converted to tetrapropanoporphyrins via a cyclotetramerization procedure. The alkyl substituents again decreased the yields, although 5-alkyl substituents were found to have a far less deleterious effect than 6-alkyl groups. In addition to providing samples to help assign the vibrational spectra of geoporphyrin samples, these results demonstrate that highly substituted porphyrin systems can be prepared from tetrahydroindole derivatives.     

The influence of exocyclic phosphorous substituents on the intrinsic stability of four-membered heterophosphetes: a theoretical study

Four-membered heterophosphetes such as oxaphosphetes, thiaphosphetes, and azaphosphetes have long been considered desirable target molecules for organic chemists because of their interesting structural features. In spite of extensive investigation, only one azaphosphete and one thiaphosphete have been synthesized to date. In this paper, two possible conformers of these four-membered rings, as well as their open-ring phosphorane forms with a set of exocyclic substituents and a few ring heteroatoms were studied by molecular computations. The results suggested that the relative stability of these compounds is strongly dependent on the electronic effect of the exocyclic P-substituents. Three different types of exocyclic substituents X were recognized. However, only the strong electron-withdrawing substituents (X=F, CN, OCN, SCN) were able to stabilize the ring forms, providing the possibility to design stable heterophosphetes on the basis of the present computational results.     

A direct method for the alkylation of adenosine nucleosides at position 8.

Alkylation of adenosine derivatives at carbon 8 can be conveniently achieved by lithiation followed by reaction with an alkyl halide.     

6-Azauracil or 8-aza-7-deazaadenine nucleosides and oligonucleotides: the effect of 2'-fluoro substituents and nucleobase nitrogens on conformation and base pairing

The stereoselective syntheses of 6-azauracil- and 8-aza-7-deazaadenine 2'-deoxy-2'-fluoro-beta-d-arabinofuranosides and employing nucleobase anion glycosylation with 3,5-di-O-benzoyl-2-deoxy-2-fluoro-alpha-d-arabinofuranosyl bromide as the sugar component are described; the 6-azauracil 2'-deoxy-2'-fluoro-beta-d-ribofuranoside was prepared from 6-azauridine via the 2,2'-anhydro intermediate and transformation of the sugar with DAST. Compounds show a preferred N-conformer population (100% N for , and 78% N for ) being rather different from nucleosides not containing the combination of a fluorine atom at the 2'-position and a nitrogen next to the glycosylation site. Oligonucleotides incorporating and were synthesized using the phosphoramidites and . Although the N-conformation is favoured in the series of 6-azauracil- and 8-aza-7-deazaadenine 2'-deoxy-2'-fluoroarabinonucleosides only the pyrimidine compound shows an unfavourable effect on duplex stability, while oligonucleotide duplexes containing the 8-aza-7-deazaadenine-2'-deoxy-2'-fluoroarabinonucleoside were as stable as those incorporating dA or 8-aza-7-deaza-2'-deoxyadenosine .     

The effect of substituents at silicon on the cross-metathesis of trisubstituted vinylsilanes with olefins

Efficient cross-metathesis of vinylsilanes, carrying a large spectrum of different substituents at silicon, with various olefins in the presence of the first and second generation Grubbs catalyst and Hoveyda–Grubbs catalyst is described. On the basis of the results of equimolar reactions of vinylsilanes with ruthenium alkylidene complexes and experiments with deuterium-labelled reagents, a general, metallacarbene mechanism for the cross-metathesis of trisubstituted vinylsilanes with olefins has been suggested. Reaction was proved to be a valuable method for synthesis of unsaturated organosilicon derivatives.     

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).     

The effect of substituents on the structure of dioxirane

Ab initio calculations have been performed for methyl- and fluorine-substituted dioxirane to analyze the influence of the substituents on the molecular structure and the peroxy bond. Fluorine substitution increases the O-O bond length and shortens the C-O bond, while methyl substitution does not introduce significant changes. These results are discussed using a molecular orbital interaction diagram. Both substituents affect the basicity of the molecule, and it is concluded that the peroxy bond is stabilized on methyl substitution since the methyl group acts as an electron donor, while fluorine substitution destabilizes the peroxy bond.     

The effect of polar substituents on the heterocyclic benzoxazoles

The synthesis, characterization, and mesomorphic properties of a new type of heterocyclic compounds 1, 2 derived from benzoxazole are reported. In order to understand the relationship between the structure and the mesomorphic behavior, compounds containing a variety of polar substituents (i.e., X=H, F, Cl, Br, CH₃, CF₃, OCH₃, NO₂, CN, OH, NMe₂, COOCH₃) on the terminal end were prepared. The phase behavior of these mesogenic compounds was characterized and studied by differential scanning calorimetry (DSC) and polarization optical microscopy. The formation of mesophases was strongly dependent on the electronic and/or the steric factors of the substituents. In general, a mesophase was better induced by introduction of a polar substituent. Compounds (X=H) formed a crystalline phase, however, other compounds, except for X=OH, exhibited nematic or smectic A phases. Interestingly all compounds with electron-donating substituents (X=CH₃, OCH₃, NMe₂) exhibited nematic phases, however, other compounds with electron-withdrawing substituents (X=F, Cl, Br, CF₃, NO₂, CN, COOCH₃) formed smectic A phases. Compounds (X=NO₂, CN, COOCH₃) have higher clearing temperatures than those of other homologues, and the higher T_cl was attributed to an enhanced conjugative interaction. However, no linear correlation between the clearing temperature or the temperature range of mesophases with Hammett σ_p constants was found. The fluorescent properties of the compounds were examined. All λ_max peaks of the absorption and photoluminescence spectra of compounds occurred at ca. 348-381 and 389-478 nm, respectively. Whereas, the quantum yields of some compounds were relatively low.     

Studies aimed at the total synthesis of azadirachtin. A modeled connection of C-8 and C-14 in azadirachtin

[reaction: see text] Studies on the connection between the right and left segments of azadirachtin are described. The Ireland-Claisen rearrangement of Li-enolate of the modeled ester with dichlorodimethylsilane in toluene afforded the desired limonoid framework stereoselectively in good yield.