Showing papers in "Journal of The Chemical Society-perkin Transactions 1 in 2002"

Long wavelength sensitizers for europium(III) luminescence based on acridone derivatives

Abstract: The preparation of several acridone derivatives which have been shown to act as sensitizers for europium(III) luminescence at wavelengths longer than 400 nm is described. The efficiency of sensitization increases as the chromophore is held closer to the ion and the inner sphere hydration number of the ion lowered.

Calculation of Abraham descriptors from solvent–water partition coefficients in four different systems; evaluation of different methods of calculation

Abstract: Partition coefficients for a set of drug compounds have been measured in four solvent–water systems, with octanol, chloroform, cyclohexane and toluene as solvents. The data have been used to test four different methods for the calculation of the three Abraham descriptors, dipolarity/polarizability S, hydrogen bond acidity A, and hydrogen bond basicity B. The methods involved (i) the use of Microsoft ‘Solver’, (ii) use of a series of regression equations developed from compounds with known descriptors, and use of two further methods that have been developed, (iii) a program similar to Solver that we denote as ‘Descfit’, and (iv) a program that uses a set of three simultaneous equations, and which we denote as ‘TripleX’. We show that partition coefficients for a given drug in only four solvent–water systems can be used to calculate the three Abraham descriptors reliably, and we test all four methods of calculation for reproducibility and ease of use. We finally test the applicability of descriptors calculated for the set of drug compounds, to predict properties of biological importance such as human intestinal absorption and blood/brain distribution.

Sandmeyer reactions. Part 7. An investigation into the reduction steps of Sandmeyer hydroxylation and chlorination reactions

Abstract: For Sandmeyer hydroxylation and chlorination in aqueous solution, the reduction steps have been investigated by means of correlation analyses of the effects of diazonium ion substitution on the rates of reduction. For simple hydroxylation, a change of behaviour between diazonium ions substituted by electron donor groups and those substituted by electron acceptor groups is interpreted as a change within an inner-sphere process from rate-determining electron transfer to rate-determining association of the reactants. By contrast, for citrate-promoted hydroxylation, a similar change in behaviour may be interpreted as a change between inner- and outer-sphere electron transfers. For chlorination, there is no mechanistic variation within the range of substituents examined but the pattern of behaviour is consistent with an inner-sphere mechanism. The various patterns of behaviour are rationalised in terms of the effects of diazonium ion substitution and catalyst ligation on the reduction potentials and self-exchange rates of the various reacting redox couples. Comparative correlation analyses of reductions and other electrophilic reactions of diazonium ions are used to support the arguments advanced in respect of Sandmeyer reduction steps. It is suggested that the CuI reductants react via a nucleophilic bridging ligand at the diazonium Nβ to give transient Z-adducts which are the precursor complexes and that activation for electron transfer involves rotation about the N–N bond.

Tungstophosphoric acid (H3PW12O40) as a heterogeneous inorganic catalyst. Activation of hexamethyldisilazane (HMDS) by tungstophosphoric acid for efficient and selective solvent-free O-silylation reactions

Abstract: Tungstophosphoric acid (H3PW12O40) effectively activates hexamethyldisilazane for the selective silylation of primary, secondary, tertiary and phenolic hydroxy groups under solvent-free conditions at 55–60 °C.

1,3-Dipolar cycloaddition reactions of carbohydrate derived nitrones and oximes

Abstract: Covering: 1990–June 2002 This review aims to summarise key features of the synthesis and 1,3-dipolar cycloaddition reactions of carbohydrate derived nitrones and oximes, allowing access to isoxazolines and isoxazolidines. An alternative approach to these targets, which involves the reaction of non-carbohydrate dipoles with carbohydrate derived alkenes, is also described.

Binding of dipeptides and tripeptides containing lysine or arginine by p-sulfonatocalixarenes in water: NMR and microcalorimetric studies

Abstract: The water soluble p-sulfonatocalix[n]arenes (n = 4, 6 and 8) (14, 16 and 18) show glycosylaminoglycan (GAG) mimicry, being both active antithrombotics and modulators of lysyloxidase activity. In order to understand how these synthetic receptors interact with GAG receptor sequences, we have undertaken a study to thermodynamically characterize the binding of dipeptides and tripeptides bearing lysine or arginine residues by 14, 16 and 18 in aqueous buffer at pH 8.0 and 298.15 K. The association constants, enthalpies and entropies of complexation have been determined using titration microcalorimetry. The structure of the complexes in solution has been studied by 1H NMR spectroscopy. Combining the microcalorimetric data, the binding shifts and the 2D experiments, the nature of the complexation may be clarified.

Calculation of Abraham descriptors from experimental data from seven HPLC systems; evaluation of five different methods of calculation

Abstract: Solvation equations have been obtained for seven high performance liquid chromatographic (HPLC) systems, generated in the reverse phase (RP) mode with fast gradient elution. A training set of 40 compounds was used for each system. The seven equations were then used to calculate Abraham descriptors for a completely separate 40-compound test set. In this way the three descriptors dipolarity/polarizability S, hydrogen bond acidity A, and hydrogen bond basicity B were obtained. Five different procedures were used to calculate the descriptors, (i) Microsoft ‘Solver’, (ii) a program that uses a set of three simultaneous equations, and which we denote as ‘TripleX’, (iii) a program similar to Solver that we denote as ‘Descfit’, (iv) a series of regression equations developed from compounds with known descriptors and (v) a series of modified regression equations. We show that RP-HPLC data for a given compound in seven systems can be used to calculate the three Abraham descriptors reliably. We compare descriptors, and errors in the method, with those obtained from water–solvent partition systems.

A novel one pot synthesis of nitrogen containing heterocycles: an alternate methodology to the Biginelli and Hantzsch reactions

Abstract: Modified Biginelli and Hantzsch reactions were carried using environmentally benign processes. Neat reactants subjected to microwave radiation gave the required products more quickly and in better yields in comparison to traditional methodologies. The observed yields and enhancement in reaction rates are due to the solvent free conditions coupled with the use of microwave radiation.

Tungstate-exchanged Mg-Al-LDH catalyst: an eco-compatible route for the oxidation of sulfides in aqueous medium

Abstract: The catalytic oxidation of sulfides selectively to sulfoxides and/or sulfones is realised for the first time with heterogeneous tungstate-exchanged Mg-Al-LDH catalyst using 30% hydrogen peroxide in aqueous media at a faster rate in quantitative yields at room temperature. The heterogeneous catalyst showed higher activity (TOF) over its homogeneous analogues and other heterogeneous catalysts reported so far. The catalyst is well characterised by various instrumental techniques such as FT-IR spectroscopy, thermal analysis (TGA and DTA), powder XRD and chemical analysis. The catalyst is reused for six cycles with consistent activity and selectivity.

Modular fluorescence sensors for saccharides

Abstract: Modular photoinduced electron transfer (PET) sensors bearing two phenylboronic acid groups, a pyrene group and alkylene linkers, from trimethylene to octamethylene, have been prepared and evaluated. The diboronic acid systems with tetramethylene 3444 pentamethylene 3555 and hexamethylene 3666 linkers display the greatest enhancement in binding relative to monoboronic acid 4 with D-glucose. The diboronic acid system with the hexamethylene 3666 linker is particularly D-glucose selective and sensitive. Whilst the diboronic acid systems with the longer heptamethylene 3777 and octamethylene 3888 linkers display the greatest enhancement in binding relative to monoboronic acid 4 with D-galactose. All saccharide titrations were performed in methanolic aqueous solution.

An approach to 2,3-dihydropyrroles and β-iodopyrroles based on 5-endo-dig cyclisations

Abstract: A representative series of homopropargylic sulfonamides 19 and 22b have been found to undergo smooth 5-endo-dig cyclisation upon exposure to excess iodine in acetonitrile containing potassium carbonate. The resulting 4-iodo-2,3-dihydropyrroles 23 readily react with two equivalents of DBU in DMF at 20 °C to give the corresponding β-iodopyrroles 24 and 26 in excellent yields by the elimination of toluene-p-sulfinic acid. Use of less than two equivalents of base results in some loss of iodine. The iodo-2,3-dihydropyrroles 23 can be used in palladium-catalysed coupling reactions as shown by the efficient formation of the Sonogashira product 29 under mild conditions.

Low barrier hydrogen bonds in sterically modified Schiff bases

Abstract: Five derivatives of an ortho-hydroxy Schiff base (2-(N-alkyl-α-iminoethyl)phenols) with very short intramolecular hydrogen bonds (dO(H)⋯N ≤ 2.500 A) were synthesised. The crystal structures were determined. The steric repulsion of the substituted methyl group results in an unusual strengthening of the hydrogen bonds, decreasing the barrier for the proton movement within the hydrogen bridge, which leads to a delocalization of the proton position. The very strong influence of the character of the substituent in the phenol ring as well as the character of the N-alkyl chain on the proton distribution is demonstrated for these hydrogen bonds from the so-called inversion range.

A concise synthesis of carpanone using solid-supported reagents and scavengers

Abstract: Polymer-supported reagents have been applied to the synthesis of the natural product carpanone resulting in a clean and efficient synthesis without the requirement for conventional purification techniques. A new polymer-supported transition metal isomerisation catalyst is also reported.

The synthesis of 4′-aryl substituted terpyridines by Suzuki cross-coupling reactions: substituent effects on ligand fluorescence

Abstract: Several 4′-aryl-substituted 2,2′:6′,2″-terpyridines (tpy-C6H4R) have been prepared by palladium-catalysed cross-coupling of 4′-bromoterpyridine or 4′-triflate-terpyridine (triflate = trifluoromethylsulfonyloxy) with aryl boronic acids or esters, RC6H4B(OR′)2 (R = H, m-NH2, p-CHO, -NO2, -CN, -NMe2, -NPh2). The new ligand 4′-mesitylterpyridine (mesityl = 2,4,6-trimethylphenyl) was prepared in the same way. Similarly, 4′-bromophenylterpyridine (tpy-ϕ-Br) has been cross-coupled with aryl halides to generate several new biaryl-substituted terpyridines (tpy-ϕ-C6H4R where R = H, p-CN, NMe2, NPh2), together with two related compounds with pendent 3- or 4-pyridyl groups (tpy-ϕ-C6H4-py). For selected compounds, the alternative coupling strategy of reaction of a terpyridine-4-boronate or terpyridine-4-phenylboronate with the appropriate aryl halide has also been investigated (e.g. to prepare tpy-ϕ-C6H4NO2), but was generally found to be less satisfactory. All of the compounds are fluorescent in the UV region of the spectrum, the biaryl-substituted compounds being only slightly red-shifted compared to the monoaryl systems, but with the further red-shift that accompanies protonation being more significant for the former. Fluorescence lifetimes in solution are in the range 1–5 ns. The emission spectra of the aminobiphenyl-substituted compounds (tpy-ϕ-C6H4NR″2, where R″ = Me or Ph) display a large red-shift with increasing solvent polarity, suggesting the involvement of an intramolecular charge transfer state, as found previously for the two analogues omitting the phenyl ring (tpy-C6H4NR″2). In contrast to the latter, however, protonation or binding of a Lewis acidic metal ion to the aminobiphenyl compounds serves to quench almost completely their emission.

Making conjugated connections to porphyrins: a comparison of alkyne, alkene, imine and azo links

Abstract: A series of porphyrins 5–9 has been prepared, in which an aryl substituent is linked to the porphyrin via azo, imine, alkene and alkyne bridges. The strength of aryl–porphyrin electronic coupling in these systems was evaluated from the red shift and intensification of the Q band absorption and emission spectra, and from the incremental red shift on changing from the phenyl to a 4-nitrophenyl substituent. The azo link provides the strongest electronic communication between the porphyrin and the benzene ring. The crystal structures of azo compounds 5a and 5c show that the porphyrin and benzene rings are almost coplanar, whereas imine 7a and alkene 8a are significantly twisted in the solid state. Imine and alkyne linked porphyrin dimers 18 and 23 were also synthesized; the alkyne-linked dimer is much more conjugated than its imine-linked analogue.

Design, synthesis and structure of new potential electrochemically active boronic acid-based glucose sensors

Abstract: In the course of our investigations on new boronic acid based carbohydrate sensors three new boronic acids 3, 7 and 11 containing a ferrocene moiety were synthesised. Their design includes an intramolecular B–N bonding motif in order to facilitate binding at physiological pH. We report the synthesis of the compounds and our investigations on glucose complexation as studied by 13C NMR spectroscopy. The crystal structure of 2,4,6-tris[2-(N-ferrocenylmethyl-N-methylaminomethyl)phenyl]boroxin (13) (boroxin of boronic acid 3) (boroxin = cyclotriboroxane) was obtained and compared with structures obtained of 2,4,6-tris[2-(N,N-dimethylaminomethyl)phenyl]boroxin (14) and 2,2-dimethyl-1,3-diyl[2-(N,N-dimethylaminomethyl)phenyl]boronate (15). The structure of 13 shows the existence of intramolecular B–N bonds in the solid phase.

Comparison of the acid–base properties of purine derivatives in aqueous solution. Determination of intrinsic proton affinities of various basic sites

Abstract: The acidity constants of protonated 7,9-dimethylguanine, 7-methylguanosine, 7,9-dimethylhypoxanthine, 7-methylinosine, 9-methyladenine, 1,9-dimethyladenine, 7,9-dimethyladenine and 1-methyladenosine were determined in aqueous solution at 25 °C and I = 0.1 M (NaNO3). In those instances where pKa > 2 potentiometric pH titrations were used for the determinations; when pKa < 2, UV spectrophotometric and 1H-NMR shift measurements were employed (25 °C). In these latter instances, where I is often larger than 0.1 M, the H0 scale was applied to define the H+ activity of the strong acid (HClO4; HNO3). A combination of the present results with values taken from our earlier work allowed us to quantify the intrinsic acidic properties in aqueous solution of the (N1)H0 or + and (N7)H+ sites via micro acidity constant schemes for seven purine derivatives and to calculate the tautomeric ratios regarding the monoprotonated species, that is N7–N1·H versus H·N7–N1 meaning that in one isomer H+ is at the N1 site and in the other at N7. A plot of the micro acidity constants pkN7–N1H·N7–N1, which quantify the acidity of the (N7)H+ site, versus the macro acidity constants pKa/(N1)H, which largely refer to the release of the proton from the (N1)H unit, results in a straight line for the guanine and hypoxanthine derivatives. This fact allows estimation of the micro acidity constant for any related derivative provided a value for pKa/(N1)H is known. The presented results are also meaningful for nucleic acids because they quantify the acid–base properties of their individual sites.

Electrochiroptical response of a hexaarylethane derivative with a helical π-skeleton: drastic UV–Vis and CD spectral changes upon electrolysis of 4′,5′-dibromodispiro[xanthene-9,9′(9′H,10′H)-phenanthrene-10′,9″-xanthene]

Abstract: Upon two-electron oxidation of the title electron donor 1a, the elongated central C9–C10 bond [1.656(5) A (X-ray)] is cleaved to give the biphenyl-2,2′-diyl bis(xanthenylium) dye 2a2+, which regenerates the colorless dispiro compound 1a by two-electron reduction. The presence of isosbestic points in the UV–Vis spectra during the electrochemical oxidation of 1a to 2a2+ indicates the negligible steady-state concentration of the intermediate cation radical. Interconversion between optically resolved 1a and 2a2+ is accompanied by drastic changes in the CD spectra again with several isosbestic points, and racemization of (P)- and (M)-1a and (S)- and (R)-2a2+ does not occur at ambient conditions. This redox pair represents a new motif for the multi-output response system, where the electrochemical input is transduced into two independent spectral outputs.

Ab-initio quantum-mechanical GIAO calculation of the anisotropic effect of C–C and X–C single bonds—application to the 1H NMR spectrum of cyclohexane

Abstract: The anisotropic effects of the C–C single bond in ethane and various other X–C single bonds (X = OH, SH, NH2) have been quantitatively calculated as nuclear independent chemical shieldings (NICSs) in a three-dimensional grid of lattice atoms around the single bonds using the GIAO method integrated into the GAUSSIAN 98 calculation program. The shielding/deshielding areas due to the anisotropic effect have been plotted as iso-chemical-shift-surfaces (ICSSs); hereby, both direction and scale of the anisotropic effect were quantified and visualized. The results obtained are not in agreement with McConnell's point dipole model; the influence of the anisotropic effect of C–C and X–C single bonds on especially 1H chemical shifts must be reevaluated. The various magnetic contributions to the theoretical NMR shielding tensors of the axial/equatorial protons in cyclohexane were calculated by a detailed NCS-NBO analysis. The partition of the C(2)–C(3) [C(5)–C(6)] bonds at the C(1)–Hax/Hequ magnetic shielding tensors determines both position and chemical shift difference, dominated by hyperconjugation.

Novel uridin-2′-yl carbamates: synthesis, incorporation into oligodeoxyribonucleotides, and remarkable fluorescence properties of 2′-pyren-1-ylmethylcarbamate

Abstract: A convenient method for the preparation of uridin-2′-yl carbamate derivatives is described. The stable 2′-O-(imidazol-1-ylcarbonyl)-3′,5′-O-(tetraisopropyldisiloxane-1,3-diyl)uridine, prepared from uridine, was treated with primary or secondary aliphatic amines to give 2′-carbamates in high yield. After 3′,5′-O-deprotection with triethylamine trihydrofluoride, 5′-O-dimethoxytritylation, and 3′-O-phosphitylation with bis(N,N-diisopropylamino)-2-cyanoethoxyphosphine, modified phosphoramidites were obtained and used in machine-assisted synthesis of modified oligodeoxynucleotides containing uridin-2′-yl carbamate residues bearing various N-substituents. The influence of uridin-2′-yl carbamate moieties on the stability of modified oligonucleotide duplexes with complementary DNA and RNA was studied by thermal denaturation experiments. Pyrene-modified oligonucleotides showed a considerable increase in fluorescence intensity upon hybridisation to complementary RNA and interesting binding properties when hybridised to a mismatched DNA.

First application of ionic liquids in electrophilic fluorination of arenes; Selectfluor™ (F-TEDA-BF4) for “green” fluorination

Abstract: The NF fluorinating agent F-TEDA-BF4 dication salt (Selectfluor™) 1 dissolves in imidazolium-based ionic liquids [emim][OTf] 7, [emim][BF4] 8, [bmim][PF6] 9 and [bmim][BF4] 10 (assisted by sonication), providing a convenient medium for fluorination of arenes under essentially acid-free conditions in a simple set-up (no volatile solvent; simple extraction of the aromatics without aqueous work-up), from which the ionic liquid can be easily recycled and reused. Comparative studies in [emim][OTf] 7 with anisole as substrate show that 1 is superior to NFTh-BF4 (Accufluor®) 2 and that the N-fluoropyridinium salt NFPy-B2F74 is least effective. The scope of the reaction has been surveyed. Substrate selectivity (kmesitylene ∶ kdurene = 10) measured in competitive experiments in 7 is clearly indicative of a conventional polar mechanism. Substrate selectivity measured without the ionic liquid in MeCN solvent is also indicative of a polar mechanism but exhibits lower magnitude (kmesitylene ∶ kdurene = 6). Addition of dicyclohexano-24-crown-8 to the fluorination reaction mixture (1 and anisole) in 7 reduced the conversion but did not change the isomer distribution. AM1 minimization was used to model the complexation of 1 with this crown. With reactive aromatics optimal fluorination yields in ionic liquids (using 1 equivalent of the NF reagent) are around 50% (higher for naphthalene). A key control experiment suggests that the free base (produced upon transfer-fluorination) could complex to unreacted 1 (generating a bulky dimer complex which may be ineffective for fluorine transfer) in competition to N-protonation.