Energetic Tuning in Spirocyclic Conjugated Polymers.

Precise control of the energy levels in a conjugated polymer is the key to allowing their exploitation in optoelectronic devices. The introduction of spirocycles into conjugated polymers has traditionally been used to enhance their solid state microstructure. Here we present a highly novel method of energetic tuning through the use of electronically active spirocyclic systems. By modifying the size and oxidation state of a heteroatom in an orthogonal spirocycle we demonstrate energetic fine tuning in both the absorption and emission of a conjugated polymer. Furthermore, the synthesis of highly novel triplet-decker spirocyclic conjugated polymers is presented. This new method of energetic manipulation in a conjugated polymer paves the way for future application targeted synthesis of polymers with electronically active spirocycles.

Cyclisation reactions of N-cinnamoyl-9-aminoanthracenes.

N-Cinnamoyl-9-aminoanthracenes cyclise with PPA or triflic acid to form novel 2-azahexacyclo[10.6.6.0(1,5).0(6,11).0(13,18).0(19,24)]tetracosa-6(11),7,9,13,15,17,19(24),20,22-nonaen-3-ones. In contrast, both N-cinnamoyl-N-methyl-9-(2-aminomethyl)anthracene and N-cinnamoyl-9-(2-aminoethyl)anthracene undergo an intramolecular Diels-Alder cycloaddition.

The triflic acid-mediated cyclization reactions of N-cinnamoyl-1-naphthylamines.

N-cinnamoyl-1-naphthylamines undergo a cyclization reaction with triflic acid to form 4-phenyl-3,4-dihydro-1H-naphth[1,8-bc]azepin-2-ones and 4-phenyl-3,4-dihydro-1H-benzo[h]quinolin-2-ones. However, the N-benzyl analogues also undergo a unique cascade reaction to form novel heptacyclic structures via a 1,2-addition followed by a 4-addition to the naphthalene. With an electron-rich N-benzyl substituent, the heptacycle is the sole product.

The acid-mediated ring opening reactions of α-aryl-lactams.

4-Aryl-azetidin-2-ones (ß-lactams) undergo ring opening with triflic acid to give cinnamamides which, in benzene, react further to give 3-aryl-3-phenyl-propionamides. Prolonged reaction times in benzene give 3,3-diphenyl-propionamide via an aryl/phenyl exchange. Lactams of ring size 7 and higher also ring open, but only 7- and 8-membered rings give pure diphenylalkylamides. AlCl(3) only ring opens the 4-aryl-azetidinones.

Structures in solutions from joint experimental-computational analysis: applications to cyclic molecules and studies of noncovalent interactions.

The potential of an approach combining nuclear magnetic resonance (NMR) spectroscopy, molecular dynamics (MD) simulations, and quantum mechanical (QM) calculations for full structural characterizations in solution is assessed using cyclic organic compounds, namely, benzazocinone derivatives 1-3 with fused five- and eight-membered aliphatic rings, camphoric anhydride 4, and bullvalene 5. Various MD simulations were considered, using force field and semiempirical QM treatments, implicit and explicit solvation, and high-temperature MD calculations for selecting plausible molecular geometries for subsequent QM geometry optimizations using mainly B3LYP, M062X, and MP2 methods. The QM-predicted values of NMR parameters were compared to their experimental values for verification of the final structures derived from the MD/QM analysis. From these comparisons, initial estimates of quality thresholds (calculated as rms deviations) were 0.7-0.9 Hz for (3)J(HH) couplings, 0.07-0.11 Å for interproton distances, 0.05-0.08 ppm for (1)H chemical shifts, and 1.0-2.1 ppm for (13)C chemical shifts. The obtained results suggest that the accuracy of the MD analysis in predicting geometries and relative conformational energies is not critical and that the final geometry refinements of the structures selected from the MD simulations using QM methods are sufficient for correcting for the expected inaccuracy of the MD analysis. A unique example of C(sp(3))-H···N(sp(3)) intramolecular noncovalent interaction is also identified using the NMR/MD/QM and the natural bond orbital analyses. As the NMR/MD/QM approach relies on the final QM geometry optimization, comparisons of geometric characteristics predicted by different QM methods and those from X-ray and neutron diffraction measurements were undertaken using rigid and flexible cyclic systems. The joint analysis shows that intermolecular noncovalent interactions present in the solid state alter molecular geometries significantly compared to the geometries of isolated molecules from QM calculations.

Triflic acid-mediated phenylation of N-acylaminoalkyl diethylacetals and N-acyl-2-phenyl cyclic amides.

The reaction of N-acylaminoalkyl diethylacetals with triflic acid in benzene gave N-acylamino-diphenylalkyls. The proposed intermediates are the N-acyl-2-phenyl cyclic amides, which themselves are similarly converted to N-acylamino-diphenylalkyls.

A novel synthesis of (di)-benzazocinones via an endocyclic N-acyliminium ion cyclisation.

The triflic acid-mediated endocyclic N-acyliminium ion cyclisation provides a facile synthesis of (di)-benzazocinones. On reduction of the 10-phenyl derivative, an unusually non-polar tertiary alkylamine was obtained.

A facile synthesis of dibenzopyrroloazepinones as tetracyclic allocolchicinoids--an unusual 1,2-phenyl shift.

A facile synthesis of dibenzopyrroloazepinones via an electrophilic cyclisation of a biphenyl-acyliminium ion is described; an unusual 1,2-phenyl shift occurs when the C-1' carbon is the more nucleophilic than the C-2' carbon.

An investigation into the electrophilic cyclisation of N-acyl-pyrrolidinium ions: a facile synthesis of pyrrolo-tetrahydroisoquinolones and pyrrolo-benzazepinones.

The triflic acid-mediated cyclisation of N-arylmethyl- and N-arylethyl-acylpyrrolidinium ions gave moderate to good yields of pyrrolo-tetrahydroisoquinolones and pyrrolo-benzazepinones respectively. Electron-donating R substituents enhanced the rate of reaction and gave higher yields than electron-withdrawing substituents. Substituents on the methyl or ethyl chain in general enhanced the reaction, unless sterically encumbered. The equivalent acylpiperidinium ions cyclised much slower and in lower yield.

A facile synthesis of pyrrolo-(di)-benzazocinones via an intramolecular N-acyliminium ion cyclisation.

A facile, moderate to high yielding synthesis of hexahydro-(di)-benzazocinones is described via an intramolecular N-acyliminium ion cyclisation. The iminium ion intermediates are formed from the readily available 4,4-diethoxybutyl amides with an excess of triflic acid. For electron-withdrawing substituents, better yields were obtained from the pre-formed 2-hydroxypyrrolidine amides. From NMR studies, at ambient temperatures the pyrrolo-benzazocin-3-ones exist as a slowly equilibrating mixture of two conformations.

The identification of potent, selective and CNS penetrant furan-based inhibitors of B-Raf kinase.

Modification of the potent imidazole-based B-Raf inhibitor SB-590885 resulted in the identification of a series of furan-based derivatives with enhanced CNS penetration. One such compound, SB-699393 (17), was examined in vivo to challenge the hypothesis that selective B-Raf inhibitors may be of value in the treatment of stroke.

The identification of potent and selective imidazole-based inhibitors of B-Raf kinase.

A novel triarylimidazole derivative, SB-590885 (33), bearing a 2,3-dihydro-1H-inden-1-one oxime substituent has been identified as a potent and extremely selective inhibitor of B-Raf kinase.

A series of bisaryl imidazolidin-2-ones has shown to be selective and orally active 5-HT2C receptor antagonists.

Bisaryl cyclic ureas have been identified as high affinity 5-HT2C receptor antagonists with selectivity over 5-HT2A and 5-HT2B. Compounds such as 8 and 22 have shown oral activity in a centrally mediated pharmacodynamic model of 5-HT2C function in rodents.

Bicyclic piperazinylbenzenesulphonamides are potent and selective 5-HT6 receptor antagonists.

The synthesis of novel 3-(octahydropyrido[1,2-a]pyrazin-2-yl)- and 3-(hexahydropyrrolo[1,2-a]pyrazin-2-yl)phenyl-2-benzo[b]thiophene sulphonamide derivatives 3, (S)-4 and (R)-4 is described. The compounds show high affinity for the 5-HT6 receptor, excellent selectivity against a range of other receptors and good brain penetration.