Uncatalysed Oxidative C‒H Amination of 9,10-Dihydro-9-Heteroanthracenes: A Mechanistic Study

A new method for the one-step C‒H amination of xanthene and thioxanthene with sulfonamides is reported, without the need for any metal catalyst. A benzoquinone is employed as a hydride (or two-electron and one-proton) acceptor. Moreover, a previously unknown and uncatalysed reaction between iminoiodanes and xanthene, thioxanthene and dihydroacridines (9,10-dihydro-9-hetero-anthracenes or dihydroheteroanthracenes) is disclosed. The reactions proceed via hydride transfer from the heteroarene substrate to the iminoiodane or benzoquinone, followed by conjugate addition of the sulfonamide to the oxidized heteroaromatic compounds. These findings may have important mechanistic implications for metal-catalysed C‒H amination processes involving nitrene transfer from iminoiodanes to dihydroheteroanthracenes. Due to the weak C‒H bond, xanthene is an often-employed substrate in mechanistic studies of C‒H amination reactions, which are generally proposed to proceed via metal-catalysed nitrene insertion, especially for reactions involving nitrene or imido complexes that are less reactive (i.e. less strongly oxidizing). However, these substrates clearly undergo non-catalysed (proton-coupled) redox coupling with amines, thus providing alternative pathways to the widely assumed metal-catalysed pathways.

Uncatalysed Oxidative C‒H Amination of 9,10-Dihydro-9-Heteroanthracenes: A Mechanistic Study

A new method for the one-step C‒H amination of xanthene and thioxanthene with sulfonamides is reported, without the need for any metal catalyst. A benzoquinone is employed as a hydride (or two-electron and one-proton) acceptor. Moreover, a previously unknown and uncatalysed reaction between iminoiodanes and xanthene, thioxanthene and dihydroacridines (9,10-dihydro-9-hetero-anthracenes or dihydroheteroanthracenes) is disclosed. The reactions proceed via hydride transfer from the heteroarene substrate to the iminoiodane or benzoquinone, followed by conjugate addition of the sulfonamide to the oxidized heteroaromatic compounds. These findings may have important mechanistic implications for metal-catalysed C‒H amination processes involving nitrene transfer from iminoiodanes to dihydroheteroanthracenes. Due to the weak C‒H bond, xanthene is an often-employed substrate in mechanistic studies of C‒H amination reactions, which are generally proposed to proceed via metal-catalysed nitrene insertion, especially for reactions involving nitrene or imido complexes that are less reactive (i.e. less strongly oxidizing). However, these substrates clearly undergo non-catalysed (proton-coupled) redox coupling with amines, thus providing alternative pathways to the widely assumed metal-catalysed pathways.

An efficient synthesis of novel triazoles incorporating barbituric motifs via [3+2] cycloaddition reaction: An experimental and theoretical study

In this work, the synthesis of novel triazole derivatives with barbituric motifs in good yields is described. The alkyne was prepared through the Knoevenagel reaction of barbituric derivatives with ortho and para O-propargylated hydroxybenzaldehyde. The mechanism and regioselectivity of this [3+2] cycloaddition reaction were investigated using the density functional theory at the B3LYP/6-31+G(d) level of theory. The computational studies revealed that a di-copper catalyzed stepwise mechanism, involving six-membered ring intermediate, is the preferred pathway. The regioselectivity was explained in terms of frontier molecular orbital (FMO) interactions, local and global electrophilicity and nucleophilicity indices. Accordingly, the favored interactions for di-copper acetylide are in good agreement with the observed regioselectivity, while completely opposite results were obtained for a possible uncatalysed reaction.

Variation of the axial haem ligands and haem-binding motif as a probe of the Escherichia coli c-type cytochrome maturation (Ccm) system

Cytochromes c are typically characterized by the covalent attachment of haem to polypeptide through two thioether bonds with the cysteine residues of a Cys-Xaa-Xaa-Cys-His peptide motif. In many Gram-negative bacteria, the haem is attached to the polypeptide by the periplasmically functioning cytochrome c maturation (Ccm) proteins. Exceptionally, Hydrogenobacter thermophilus cytochrome c552 can be expressed as a stable holocytochrome both in the cytoplasm of Escherichia coli in an apparently uncatalysed reaction and also in the periplasm in a Ccm-mediated reaction. In the present study we show that a Met60→Ala variant of c552, which does not have the usual distal methionine ligand to the haem iron of the mature cytochrome, can be made in the periplasm by the Ccm system. However, no holocytochrome could be detected when this variant was expressed cytoplasmically. These data highlight differences between the two modes of cytochrome c assembly. In addition, we report investigations of haem attachment to cytochromes altered to have the special Cys-Trp-Ser-Cys-Lys haem-binding motif, and Cys-Trp-Ser-Cys-His and Cys-Trp-Ala-Cys-His analogues, of the active-site haem of nitrite reductase NrfA.

Potential Catalysts for the Acetylation of Wood

Summary The potential of several tertiary amine catalysts (pyridine, 4-dimethyl-amino pyridine, N-methyl pyrrolidine and N-methyl pyrrolidinone) for the acetylation of Corsican pine sapwood, using acetic anhydride, has been investigated. Rates of reaction were compared with non-catalysed acetylation using acetic anhydride. The hypernucleophile 4-dimethylamino pyridine was found to be the most effective catalyst of those studied. At a concentration of only 1% of the catalyst in acetic anhydride, a weight percent gain of 20% was realised, compared with 7% for the uncatalysed reaction, after 30 minutes system at 100°C. The influence of substrate swelling upon the rate of reaction with wood is discussed.

MINDO Forces Study of the Uncatalysed and Acid-Catalysed Friedel-Crafts Reactions Between CH3F and CH4

MINDO-forces calculations have been performed on the uncatalysed and acid-catalysed Friedel-Crafts reaction between CH3F and CH4 . It has been found that the catalysed reaction is exothermic, spontaneous and has a smaller potential-energy barrier than the uncatalysed reaction. The mechanisms for uncatalysed and catalysed reactions are discussed.

Noble gas catalysed 1,2-migrations in N2H+ and N2CH3+

Molecular orbital calculations are reported for N2H+ and N2CH3+ and for the transition structures for the rearrangement of these ions by 1,2-shifts of H and CH3. All reaction profiles were also calculated with one atom of noble gas, M, present (M = Ne, Ar, Kr). Structure optimizations were performed at B3LYP/6-311++G(d,p) and, in the case of N2H+···M, single point calculations were also performed at QCISD(T)(full)/6-311++G(2df,p). For N2H+, inclusion of one noble gas atom reduces the barrier to rearrangement from 46.6 kcal mol-1 for the uncatalysed reaction to 42.6 kcal mol-1 (by Ne), to 21.4 kcal mol-1 (by Ar), and to 11.0 kcal mol-1 (by Kr). For N2CH3+, the barrier of 36.4 kcal mol-1 is reduced to 35.1 kcal mol-1 by Ne, to 27.4 kcal mol-1 by Ar, and to 18.4 kcal mol-1 by Kr.Key words: catalysis, molecular orbital theory, argon, krypton.

Heterologous expression, purification and characterization of rat class theta glutathione transferase T2-2

Rat glutathione transferase (GST) T2-2 of class Theta (rGST T2-2), previously known as GST 12-12 and GST Yrs-Yrs, has been heterologously expressed in Escherichia coli XL1-Blue. The corresponding cDNA was isolated from a rat hepatoma cDNA library, ligated into and expressed from the plasmid pKK-D. The sequence is the same as that of the previously reported cDNA of GST Yrs-Yrs. The enzyme was purified using ion-exchange chromatography followed by affinity chromatography with immobilized ferric ions, and the yield was approx. 200 mg from a 1 litre bacterial culture. The availability of a stable recombinant rGST T2-2 has paved the way for a more accurate characterization of the enzyme. The functional properties of the recombinant rGST T2-2 differ significantly from those reported earlier for the enzyme isolated from rat tissues. These differences probably reflect the difficulties in obtaining fully active enzyme from sources where it occurs in relatively low concentrations, which has been the case in previous studies. 1-Chloro-2,4-dinitrobenzene, a substrate often used with GSTs of classes Alpha, Mu and Pi, is a substrate also for rGST T2-2, but the specific activity is relatively low. The Km value for glutathione was determined with four different electrophiles and was found to be in the range 0.3 mM–0.8 mM. The Km values for some electrophilic substrates were found to be in the micromolar range, which is low compared with those determined for GSTs of other classes. The highest catalytic efficiency was obtained with menaphthyl sulphate, which gave a kcat/Km value of 2.3×106 s-1·M-1 and a rate enhancement over the uncatalysed reaction of 3×1010.