Search

Arene and heteroarenediazonium o-benzenedisulfonimides can be used as efficient reagents in Sandmeyer cyanation. This work reports such reactions carried out by us under very mild conditions using tetrabutyl ammonium cyanide as a safe cyanide source and, interestingly, without the need for a Cu catalyst. The reactions have given rise to aryl nitriles in good yields (25 examples, average yield 75%). A good amount of o-benzenedisulfonimide was recovered from each reaction and then reused to prepare other salts. Mechanistic insights have allowed us to highlight the fundamental role of the o-benzenedisulfonimide anion as an electron transfer agent.

This gives exclusively the E isomers of the arylidene-hetarylium tetrafluoroborates, which can be easily reduced to the corresponding aryl-hetaryl-methanes.

Title diazonium salts are used for the first time as electrophilic partners in Negishi cross coupling reactions to produce biaryls.

Arenediazonium o-benzenedisulfonimides (I) are found to be suitable substrates in Sonogashira coupling.

The inhibitory activity of Calyxamine B (II) on acetylcholinesterase is comparable to the natural inhibitors.

This review deals with results from crystallographic studies on proteins that interact with the essential micronutrient cobalamin (vitamin B12). Both B12-dependent enzymes and B12-transport proteins are described with an emphasis on structural aspects of cobalamin and its protein environment.

A new application of the recyclable and reusable catalyst (for five times) is presented for the very simple, efficient, and green title reaction, which includes an easy work-up procedure.

Cobaloximes are bis(dioximate) cobalt complexes with the metal ion having different oxidation and coordination numbers. The most common cobaloximes are octahedral complexes of formula trans-LCo(dioxH)2X, where dioxH is the dioxime monoanion, L a neutral ligand and X a monoanionic ligand. Due to the possibility to obtain and characterize CoIII compounds with a large variety of dioxH, X and L ligands, they constitute a unique system of octahedral cobalt complexes. The availability of a large number of complexes has allowed to rationalize their structural properties in solution and in the solid state and their reactivity in term of cis and trans influences and effects. These studies were also prompted by the widely accepted proposal that cobaloximes are model systems of cobalamins, the cofactors of B12 enzymes. Cobaloximes behave as functional models of cobalamin also towards the reductive dechlorination of chloroethylenes. Alkylcobaloximes have catalytic applications in organic chemistry and in polymerization reactions. Recently, inorganic cobaloximes have been studied as catalysts for the hydrogen evolution in the presence of a proton source. All these aspects of cobaloximes and of some related compounds, such as dioximate chlatrochelates, are presented in this chapter. Keywords: Cobaloximes; Structure; Properties; Reactivity; Cis Influence/effect; Trans influence/effect; B12 model systems; Polymerization catalysts; Hydrogen evolution

Galvanostatic reduction of a solution of acetonitrile and Et4NPF6 generates an acetonitrile anion as selective reagent in the alkylation of bifunctional substrates with alkyl bromides.

Treatment of the indole (I) with aromatic aldehydes and the imine (II) allows access to new stable title compounds like (IV).

Benzodithioles (VII), disulfonyl chlorides (VIII), and the target benzenedisulfonimides (IX) exhibit atropisomerism due to the hindered rotation of the aryl group.

In the case of less reactive aliphatic aldehydes, the corresponding dimethylacetals are used.

The synthesis of tetrahydroisoquinolines and tetrahydro-β-carbolines, using the Pictet–Spengler reaction, was carried out in the presence of a catalytic amount of o -benzenedisulfonimide, which worked as a Bronsted acid organocatalyst. The reaction conditions were mild and green and good target product yields were achieved. The catalyst was easily recovered and purified, ready to be used in further reactions with economic and ecological advantages.

Plants of the Hypericum genus (Clusiaceae) have been known around the world for centuries for their medicinal properties. While H. perforatum (St. John’s wort), used to treat moderate depression,[1] is perhaps the most famous of these species, H. Chinense is the most recent member of this family of plants to receive notoriety as the source of biyouyanagin A. A potent anti-HIV agent and a lipopolysaccharide-induced cytokine production inhibitor, this novel natural product was first reported by Tanaka and co-workers in 2005 as possessing structure 1′ (Figure 1a).[2] Following our total synthesis of biyouyanagin A (1) from ent-zingiberene (ent-3) and hyperolactone C (4), through a [2+2] photocycloaddition, and revision of its structure from 1′ to 1 (Figure 1a),[3,4] a second biyouyanagin (B) was isolated from the same species and reported by the same group as possessing structure 2′ (Figure 1b) on the basis of spectroscopic and mass spectrometric analysis.[5] We now report the total synthesis and structural revision of biyouyanagin B (from 2′ to 2, Figure 1b) as well as the synthesis of several new biyouyanagins not yet discovered in nature, despite their possible existence based on biosynthetic considerations.

Arene mono- and disulfonyl chlorides have been easily synthesized starting from the corresponding anilines via aqueous oxidative chlorination of S-aryl O-ethyl dithiocarbonates intermediates, aryl methyl sulfides, or from arenethiols.

A thorough study of the synthesis of 2,4-diacylpyrroles by direct acylation of pyrrole and 2- and 3-acylpyrroles is reported. Among these, Friedel–Crafts acylation of 3-acylpyrroles is the most general and advantageous method because it utilises easily accessible starting materials. In addition it is always regiospecific and readily provides 2,4-diacylpyrroles containing identical or different acyl groups in very high yields (81–100%) under mild conditions. Alternative procedures concern the synthesis of precursors of 2,4-diacylpyrroles containing one or two acyl groups masked by a 1,3-benzodithiolyl or 1,3-benzoxathiolyl group and subsequent hydrolysis with HgO–35% aq. HBF4Me2SO. Overall yields are always good (52–60%). Indirect acylation constitutes a secure complement to direct acylation when it is necessary to operate in the presence of protected acyl groups.

A series of dihydro-1H-pyrrolo[1,2-a]imidazole-2,5(3H,6H)-diones were synthesized. These bicylic derivatives contain both the 2-pyrrolidinone and 4-imidazolidinone nuclei, already recognized as important for cognition enhancing activity. In addition, these structures maintain the backbone of piracetam and oxiracetam with the acetamide side chain restricted in a folded conformation. Their ability to reverse scopolamine-induced amnesia was assessed in a one trial, step-through, passive avoidance paradigm. The main features observed are a potent antiamnestic activity after ip administration (minimal effective dose being between 0.3 and 1 mg/kg ip for most compounds), the presence of a bell-shaped dose-response curve and, generally, a reduction of biological activity after po administration. However, the unsubstituted compound (15, dimiracetam) shows no evidence of a bell-shaped dose-response curve and completely retains activity when given orally, being 10-30 times more potent than the reference drug oxiracetam.

A new general method for the synthesis of pyrrole-2,5-dicarbaldehyde and its 3-mono- and 3,4-disubstituted derivatives is reported. It involves the intermediate formation of the corresponding 2,5-bis(1,3-benzodithiol-2-yl)pyrroles followed by hydrolysis with HgO–35% aq. HBF4–DMSO. Pyrrole-2,5-dicarbaldehyde was obtained in overall yields of 43–65%, whilst that of the derivatives was 32–90%. Moreover the methylation of the corresponding dithiolic intermediate with further hydrolysis resulted in the formation of 1-methylpyrrole-2,5-dicarbaldehyde in 90% overall yield.

A thorough study directed towards the synthesis of methyl thiolcarboxylates was made on the basis of the following steps: (i) conversion of alkyl halides into the corresponding trimethyl trithioorthocarboxylates by using tris(methylthio)methyllithium in THF at –78 °C; (ii) selective hydrolysis of the intermediates to methyl thiolcarboxylates by using 35% aq. HBF4 in DMSO or, in some cases, in THF. The overall yields of the two stages are, usually, between 70 and 88%. By this procedure it is also possible to incorporate 8O in the carbonyl group of thiol esters (∼98% isotopic purity). Furthermore, a new, convenient method for the preparation of tris(methylthio)methane as the precursor of tris(methylthio)methyllithium was developed.

3-Substituted and 3,4-disubstituted pyrrole-2,5-dicarbaldehydes have been obtained by hydrolysis with HgO–35% aq. HBF4–DMSO of the intermediates 4 and 5 prepared by electrophilic substitution reactions on 2,5-bis(1,3-benzodithiol-2-yl)pyrrole. The overall yields starting from pyrrole ranged from 41–88%.

Tricyclic compounds with an imidazolinone ring fused to 1,2- and 1,4-naphtoquinones were synthesized by a reaction of 4-amino-1,2-naphthoquinone and 2-amino-1,4-naphthoquinone with electrophilic symmetric and non symmetric diazenes.

The synthesis of Z- and E-arylhydrazones by 1,4-conjugate addition of glycine, L-alanine and L-tyrosine ethyl esters to phenylazostilbene 1, p-nitrophenylazostilbene 2 and p-nitrophenylazocyclohexene 3 is described. Optically active N-functionalized 2-aminocyclohexanones 22–26 are obtained by TiCl3 catalysed hydrolysis of the corresponding hydrazones. However, they have been shown to be unstable, as they undergo easy oxidation by air. X-Ray analysis of the phenylhydrazone 8a in the Z configuration is also reported.

A number of trans-3-acetyl-4-alkylpyrrolidin-2-ones 8a–d and 11a,b were prepared and reduction of the keto group, carried out with KBH4 in CH3OH, led mainly to 3-hydroxyethylpyrrolidin-2-ones 13a–d and 19a,b with high stereoselection. Configuration of the newly formed stereogenic centre on the hydroxyethyl chain was assigned by 1H NMR data supported by molecular mechanic calculations and eventually confirmed by X-ray diffraction analysis of p-iodobenzoate derivative 15.

[formula: see text] Synthesis of four novel thieno derivatives 4-7 featuring the codeine skeletal backbone is reported. Characterization by 1H and 13C NMR is also discussed, along with binding profile for opioid receptors.

In the last decade a number of selective and potent non-peptidic agents became available to explore the usefulness of the δ-opioid receptor in modulation of pain of different origins. As a continuing effort in this field, potent and selective δ-opioid agonists based on the pyrrolomorphinan framework have been designed, synthesised and characterised biologically in our laboratories. In animal models, a selected compound of interest, SB 235863, has proved the concept that selective δ-opioid agonists may have great potential as pain relief agents in inflammatory and neuropathic pain conditions. Importantly, such a compound was free of the unwanted side effects usually associated with narcotic analgesics such as morphine.

One-electron electrochemical reduction of the salts 1-benzyl-3,5-bis(methylcarbamoyl)pyridinium bromide 3a and 1-benzyl-3,5-dicarbamoylpyridinium bromide 3b yields mixtures of four isomeric dimers, as shown by HPLC analysis and mass spectrometry. 1H and 13C NMR spectrometry allows us to determine the structures of the mixture components. In both mixtures, the two most abundant products are identified as 4,4′- and 2,4′-tetrahydrobipyridines (5a, 5b and 6a, 6b, respectively), while minor amounts of a pair of diastereomeric 2,2′-linked dimers are also detected in (7a, 8a and 7b, 8b respectively). Therefore, the NMR studies lead to the conclusion that the structure assignment of conformers of 5a, made previously for 6a and 7a, is not correct. All the 2,2′- and 2,4′-linked dimers undergo photochemical dissociation into two pyridinyl radicals which recombine to yield 4,4′-linked dimers.

o-Benzenedisulfonimide has been used for the first time as a Bronsted acid catalyst to induce electrocyclization of dienones into cyclopentenones (Nazarov reaction). The catalyst has been used in various organic solvents or under solvent-free conditions and it is entirely recoverable from the reaction mixture. The versatility and the effectiveness of the proposed procedure is demonstrated on a wide range of both activated and inactivated substrates.

The reaction of various arenediazonium o-benzenedisulfonimides with aliphatic triorganoindium compounds is described. Surprisingly, with triethyl- or tributylindium we obtained N-ethyl- or N-butylanilines, respectively. This is the first case in which, at least formally, the reactive site of a diazonium salt is the nitrogen atom directly bonded to the aromatic ring. In contrast, with trimethylindium we obtained only formaldehyde (aryl)hydrazones. In order to explain the difference between trimethyl- and triethylindium we have proposed some reaction mechanisms, supported by detailed density functional (DFT) calculations. The possible role of diazene/hydrazone tautomerism initially assumed was discarded and therefore three mechanisms for the key step (nucleophilic addition of the trialkylindium to the N=N double bond of diazene) were studied. For the favoured mechanism there is a difference in the energy barriers of 2 kcal mol–1 between the reactions with trimethyl- and triethylindium. This difference is explained on the basis of the different C–In bond energies in the two organometallics and it is assumed to be enough to explain their different behaviour under the experimental conditions.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)

Arenediazonium o-benzenedisulfonimides were reacted with tetramethyltin, tetrabutyltin or trialkylboranes. The reactions, carried out in the presence of palladium(II) derivatives as precatalysts, gave the methylation and alkylation products with good overall conversions. The o-benzenedisulfonimide was recovered in high yield from all the reactions and could be recycled for the preparation of other salts.

This paper reports a novel methodology for the conformational analysis of [2]rotaxanes. It combines NMR spectroscopic (COSY, NOESY and the recently reported paramagnetic line-broadening and suppression technique) and electrochemical techniques to enable a quantitative analysis of the co-conformations of interlocked molecules and the conformations of their components. This methodology was used to study a model [2]rotaxane in solution. This [2]rotaxane consists of an axle that incorporates an electron-poor, doubly positively charged viologen that threads an electron-rich crown ether. It has been shown that the axle of the [2]rotaxane in its dicationic state adopts a folded conformation in solution and the crown ether is localised at the viologen moiety. Following a one-electron reduction of viologen, the paramagnetic radical cation of the [2]rotaxane retains its folded conformation in solution. The data also demonstrate that in the radical cation the crown ether remains localised at the viologen, despite its reduced affinity for the singly reduced viologen. The combined quantitative NMR spectroscopic and electrochemical characterisation of the electromechanical function of the model [2]rotaxane in solution provides an important reference point for the study of switching in structurally related bistable [2]rotaxanes, which is the subject of the second part of this work.

The O-benzenedisulfonimide is used as Bronsted acid in catalytic amounts in various acid-catalyzed organic reactions, such as etherification, esterification, and acetalization; the conditions required are mild and in the considered examples the results are always good. A useful aspect of the use of this catalyst is its easy recovery in high yield from the reaction mixture and its reuse in -other reactions, with economic and ecological advantages.