ABSTRACT
Small-molecule drug discovery requires reliable synthetic methods for attaching amino compounds to heterocyclic scaffolds. Trifluoroacetic acid-2,2,2-trifluoroethanol (TFA-TFE) is as an effective combination for achieving SN Ar reactions between anilines and heterocycles (e.g., purines and pyrimidines) substituted with a leaving group (fluoro-, chloro-, bromo- or alkylsulfonyl). This method provides a variety of compounds containing a "kinase-privileged fragment" associated with potent inhibition of kinases. TFE is an advantageous solvent because of its low nucleophilicity, ease of removal and ability to solubilise polar substrates. Furthermore, TFE may assist the breakdown of the Meisenheimer-Jackson intermediate by solvating the leaving group. TFA is a necessary and effective acidic catalyst, which activates the heterocycle by N-protonation without deactivating the aniline by conversion into an anilinium species. The TFA-TFE methodology is compatible with a variety of functional groups and complements organometallic alternatives, which are often disadvantageous because of the expense of reagents, the frequent need to explore diverse sets of reaction conditions, and problems with product purification. In contrast, product isolation from TFA-TFE reactions is straightforward: evaporation of the reaction mixture, basification and chromatography affords analytically pure material. A total of 45 examples are described with seven discrete heterocyclic scaffolds and 2-, 3- and 4-substituted anilines giving product yields that are normally in the range 50-90 %. Reactions can be performed with either conventional heating or microwave irradiation, with the latter often giving improved yields.
Subject(s)
Amines/chemistry , Aniline Compounds/chemistry , Heterocyclic Compounds/chemistry , Purines/chemistry , Pyrimidines/chemistry , Trifluoroacetic Acid/chemistry , Trifluoroethanol/chemistry , Catalysis , Microwaves , Molecular StructureABSTRACT
A cunning strategy has been devised for functionalizing and solubilizing subphthalocyanines at the central boron atom, so that the inherent photophysical properties remain intact. The approach, which leads to the formation of a stable B-C[triple bond]C linkage, is demonstrated by the isolation of two shape-persistent, photo-active molecular-scale dyads, each capable of multiple energy-transfer steps (see scheme, S = singlet energy transfer; T = triplet energy transfer).
ABSTRACT
Cutting the corner: An excellent agreement has been obtained between experimental and computed coulombic coupling matrix elements for donor-spacer-acceptor systems, which consist of a boron dipyrromethane donor and acceptor in various stages of protonation. This correlation occurs in spite of reservations about the validity of Förster theory being applied to intramolecular electronic energy transfer (ET) over short (e.g., 20 A) distances (see picture).
ABSTRACT
Ultrafast discharge of a single-electron capacitor: A variety of intramolecular electron-transfer reactions are apparent for polyoxometalates functionalized with covalently attached perylene monoimide chromophores, but these are restricted to single-electron events. (et=electron transfer, cr=charge recombination, csr=charge-shift reaction, PER=perylene, POM=polyoxometalate).A new strategy is introduced that permits covalent attachment of an organic chromophore to a polyoxometalate (POM) cluster. Two examples are reported that differ according to the nature of the anchoring group and the flexibility of the linker. Both POMs are functionalized with perylene monoimide units, which function as photon collectors and form a relatively long-lived charge-transfer state under illumination. They are reduced to a stable pi-radical anion by electrolysis or to a protonated dianion under photolysis in the presence of aqueous triethanolamine. The presence of the POM opens up an intramolecular electron-transfer route by which the charge-transfer state reduces the POM. The rate of this process depends on the molecular conformation and appears to involve through-space interactions. Prior reduction of the POM leads to efficient fluorescence quenching, again due to intramolecular electron transfer. In most cases, it is difficult to resolve the electron-transfer products because of relatively fast reverse charge shift that occurs within a closed conformer. Although the POM can store multiple electrons, it has not proved possible to use these systems as molecular-scale capacitors because of efficient electron transfer from the one-electron-reduced POM to the excited singlet state of the perylene monoimide.
ABSTRACT
A multi-porphyrin cluster has been covalently attached to a polyoxometallate (POM) catalyst so as to form an advanced model for the photosynthetic reaction complex. This bio-inspired mimic displays efficient energy transfer from the peripheral zinc porphyrins (ZnP) to the central free-base porphyrin (FbP). The latter species participates in a light-induced electron transfer with the POM. Charge recombination is hindered by hole transfer from the FbP to one of the ZnPs. Charge accumulation occurs at the POM under illumination in the presence of a sacrificial electron donor.
