Synthesis of 6‐amino acid substituted 4,6,7,12‐tetrahydro‐4‐oxoindolo[2,3‐a]quinolizines

In the presence of Na₂CO₃ (1S,3S)‐ and (1R,3S)‐1‐(2,2‐dimethoxyethyl)‐2‐(1,3‐dioxobutyl)‐3‐(1,3‐dioxo‐butyl)oxymethyl‐1,2,3,4‐tetrahydrocarboline ( 1 ) were transformed into (1S,3S)‐ and (1R,3S)‐1‐(2,2‐dimethoxyethyl)‐2‐(1,3‐dioxobutyl)‐3‐hydroxymethyl‐1,2,3,4‐tetrahydrocarboline ( 2 ), which were cyclized to (6S)‐3‐acetyl‐6‐hydroxymethyl‐4,6,7,12‐tetrahydro‐4‐oxoindolo[2,3‐a]quinolizine ( 4 ), via(6S,12bS)‐ and (6S,12bR)‐3‐acetyl‐2‐hydroxyl‐6‐hydroxymethyl‐1,2,3,4,6,7,12,12b‐octahydro‐4‐oxoindolo[2,3‐a]quinoline ( 3 ). (6S)‐ 4 was coupled with Boc‐Gly, Boc‐L‐Asp(β‐benzyl ester), or Boc‐L‐Gln to give 6‐amino acid substituted (6S)‐3‐acetyl‐4,6,7,12‐tetrahydro‐4‐oxoindolo[2,3‐a]quinolizines 5a , 5b , or 5c , respectively. After the removal of Boc from (6S)‐ 5a (6S)‐3‐acetyl‐6‐glycyl‐4,6,7,12‐tetrahydro‐4‐oxoindolo[2,3‐a]quinolizine ( 6 ) was obtained. The anticancer activities of (6S)‐ 5 and (6S)‐ 6 in vitro were tested.     

Synthesis and characterization of 3,4‐diaryl‐substituted polythiophene derivatives

A series of polythiophene derivatives bearing 3,4‐diaryl substituents were synthesized starting from commercially available 3,4‐dibromothiophene. The effects of two different aryl substituents, either a 5‐octyl‐2‐thienyl or a 4‐octylphenyl, were investigated in this study. To minimize steric effects on polymerization and conjugation, polymers were synthesized with a bithiophene or a triple‐bond spacer. The resulting polymers show varying solubility in common organic solvents and their UV‐visible absorption spectra in solution exhibit maxima in the range 434–484 nm, which are significantly red‐shifted as compared to those of 3,4‐dialkyl‐substituted polythiophenes. Gel permeation chromatography analysis using polystyrene standards shows a weight‐average molecular weight range of 1.50 × 10⁴–4.40 × 10⁴ g mol^?1 for the various polymers. Copyright © 2011 Society of Chemical Industry     

Synthesis of 6‐Substituted 7‐Bomoazabicyclo[2.2.1]heptanes via Nucleophilic Addition to 3‐Bromo‐1‐azoniatricyclo[2.2.1.0]‐heptane Bromide

We describe herein an efficient method for the preparation of a functionalised bicyclic framework (6‐substituted 7‐bromo‐aza‐bicyclo[2.2.1]heptane) through the selective opening of the aziridium 2 with organocuprates in up to 90% yield. These interesting chiral building blocks were then utilised as novel ligands in the rearrangement of epoxides to afford chiral allylic alcohols.     

A One‐Pot Synthesis of [1,2,4]Triazino[4,3‐b]‐[1,2,4,5]tetrazines

Reactions of hydrazonoyl halides 6 with either 4‐amino‐2,3‐dihydro‐6‐substituted‐3‐thioxo‐[1,2,4]‐triazin‐5(4H)ones 1 ( 2 ) or 4‐amino‐3‐methylthio‐6‐substituted‐[1,2,4]‐triazin‐5(4H)ones 3 ( 4 ) gave [1,2,4]‐triazino‐[4,3‐b][1,2,4,5]tetrazine derivatives 9 ( 10 ), respectively. The mechanism of the reactions studied is discussed.     

Facile Palladium‐Catalyzed Synthesis of 3‐Arylpyrazolo[1,5‐a]pyrimidines

An efficient palladium‐catalyzed synthesis of 3‐arylpyrazolo[1,5‐a]pyrimidines has been investigated. The key step in the synthesis is a Suzuki biaryl coupling of 3‐bromo‐2,5‐dimethyl‐7‐aminopyrazolo[1,5‐a]pyrimidines with arylboronic acids to provide 3‐arylpyrazolo[1,5‐a]pyrimidines in moderate to good yield. The synthetic utility of this methodology has been demonstrated by a concise and convergent synthesis of R121920, a potent CRHR₁ antagonist recently undergoing clinical evaluations.     

6‐Pyridinium benzo[a]phenazine‐5‐oxide derivatives as visible photosensitisers for polymerisation

Several 6‐pyridinium benzo[a]phenazine‐5‐oxide derivatives have been synthesised and characterised by proton nuclear magnetic resonance spectroscopy and mass spectrometry. The spectroscopic and electrochemical properties of these dyes were examined. The dyes were used as reducible sensitisers for selected electron donors (phenylthioacetic acid, phenoxyacetic acid, N‐phenylglycine, and ethyl 4‐N,N‐dimethylaminobenzoate) and as oxidisable sensitisers for electron acceptors (onium and N‐alkoxypyridinium salts). These photoredox pairs were found to be effective visible‐wavelength photoinitiators for the free radical polymerisation of trimethylolpropane triacrylate under visible light. The cationic photopolymerisation of cyclohexene oxide by the studied dyes and the onium salt photoredox pairs was ineffective. The obtained results are discussed on the basis of both free energy change for electron transfer to or from the benzo[a]phenazine dyes and the photochemical properties of the dyes, particularly their photobleaching. The proposed mechanism of dye fading is supported by density functional theory calculations and spectroscopic characterisation of the radical cation of the dye.     

Synthesis and properties of alkyl‐substituted poly(1,4‐phenylenevinylene) derivatives

The luminescent poly(2‐dodecyl‐5‐methyl‐1,4‐phenylenevinylene) was synthesized with a new synthetic route. The structure and properties of the polymers were characterized by IR, UV‐vis, luminescent spectra, GPC, and both thermal and elemental analysis. The glass‐transition temperature increases and the photoluminescent relative quantum yield decreases with the increase of the conjugation extent of the polymer. © 2001 John Wiley & Sons, Inc. J Appl Polym Sci 80: 1299–1304, 2001     

Synthesis and properties of new derivatives of poly[9‐(2,3‐epoxypropyl)carbazole]

BACKGROUND: Carbazole derivatives are well known to exhibit interesting electro‐ and photo‐active properties due to their hole‐transporting ability, strong absorption in the ultraviolet spectral region and blue‐light emission. One of the most widely studied materials among carbazole‐containing oligomers is poly[9‐(2,3‐epoxypropyl)carbazole] (PEPK). The main field of application of this oligomer is electrophotographic microfilming. It is also used for the manufacture of multicolour slides and in the photothermoplastic recording of information. Unfortunately, due to its high ionization potential, which reaches 5.86 eV, the possibilities of application of this compound in optoelectronic devices are rather limited. RESULTS: PEPK‐based charge transporting oligomers, incorporating hydrazone moieties, are reported. The oligomers were prepared by chemical modification of PEPK. The materials obtained were examined using various techniques including differential scanning calorimetry and ultraviolet, infrared and NMR spectroscopy. Electron photoemission spectra of layers of the synthesized oligomers showed ionization potentials (I_p) in the range 5.4–5.5 eV. CONCLUSION: The synthesized oligomers possess a larger π‐conjugated system and show ionization potentials of ca 5.4 eV. Therefore, they are more suitable for use in optoelectronic devices with quicker photoresponse than unmodified PEPK. Copyright © 2008 Society of Chemical Industry     

Brønsted Acid‐Catalyzed Synthesis of Pyrans via a Formal [3+3] Cycloaddition

Brønsted acids catalyze the addition of enolizable β‐keto esters to α,β‐unsaturated aldehydes leading to substituted 2H‐pyrans in good yields under mild conditions via a formal [3+3] cycloaddition.     

Improved conversion of 6‐endo‐tosyloxybicyclo[2.2.2]octan‐2‐ones into 6‐exo‐acetoxy and 6‐exo‐benzoyloxybicyclo[2.2.2]octan‐2‐ones

The reaction conditions for the conversion of 6‐endo‐tosyloxybicyclo[2.2.2]octan‐2‐one ( 7b ) into 6‐exo‐acetoxy ( 8b ) and 6‐exo‐benzoyloxybicyclo[2.2.2]octan‐2‐one ( 8a ), respectively, were improved. Thus known 6‐endo‐tosyloxy‐bicyclo[2.2.2]octan‐2‐ones (+)‐(1RS,6SR,8SR,11RS)‐11‐[(4‐toluenesulfonyl)oxy]tricyclo[6.2.2.0^1,6]dodecan‐9‐one ( 1a ), 13‐methyl‐15‐oxo‐9β,13b‐ethano‐9β‐podocarpan‐12β‐yl‐4‐toluenesulfonate ( 3a ), and methyl (13R)‐16‐oxo‐13‐[(4‐tolylsulfonyl)oxy]‐17‐noratisan‐18‐oate ( 5 ), were converted,in comparable yields, as previously recorded, but much shorter times, into (+)‐(1RS,6SR,8SR,11SR)‐11‐(benzoyloxy) tricyclo[6.2.2.0^1,6]dodecan‐9‐one ( 2 ), 13‐methyl‐15‐oxo‐9β,13β‐ethano‐9β‐podocarpan‐12α‐yl benzoate ( 4 ), and methyl (13S)‐13‐(benzoyloxy)‐16‐oxo‐17‐noratisan‐18‐oate ( 6 ), respectively.     

Preparation,characterization and selective reactions of novel [1,3]diazetidine‐2,4‐diones (uretdiones) — a new route to generate asymmetric substituted toluylenediisocyanate‐derivatives

The selective cyclodimerization of monomeric diisocyanates like IPDI 4 and TDI 5 yields [1,3]diazetidine‐2,4‐diones (uretdiones). On this basis, a new method for the selective transformation of the NCO‐groups of asymmetric substituted diisocyanates is described. The reaction with different nucleophiles yields carbamates and ureas such as 9 – 11 .     

Synthesis and characterization of novel phenyl‐substituted poly(p‐phenylene vinylene) derivatives

Two novel phenyl‐substituted poly(p‐phenylene vinylene) derivatives, poly{2‐[3′,4′‐(2″‐ethylhexyloxy)(3″,7″‐dimethyloctyloxy)benzene]‐1,4‐phenylenevinylene} (EDP‐PPV) and poly{2‐[3′,4′‐(2″‐ethylhexyloxy)(3″,7″‐dimethyloctyloxy)benzene]‐5‐methoxy‐1,4‐phenylenevinylene} (EDMP‐PPV), and their copolymer, poly{2‐[3′,4′‐(2″‐ethylhexyloxy)(3″,7″‐dimethyloctyloxy)benzene]‐1,4‐phenylene‐vinylene‐co‐2‐[3′,4′‐(2″‐ethylhexyloxy)(3″,7″‐dimethyloctyloxy)benzene]‐5‐methoxy‐1,4‐phenylenevinylene} (EDP‐co‐EDMP‐PPV; 4:1, 1:1, and 1:4), were successfully synthesized according to the Gilch route. The structures and properties of the monomers and the resulting conjugated polymers were characterized with ¹H‐NMR, ¹³C‐NMR, elemental analysis, gel permeation chromatography, thermogravimetric analysis, ultraviolet–visible absorption spectroscopy, and photoluminescence and electroluminescence (EL) spectroscopy. The EL polymers possessed excellent solubility in common solvents and good thermal stability with a 5% weight loss temperature of more than 380°C. The weight‐average molecular weights and polydispersity indices of EDP‐PPV, EDMP‐PPV, and EDP‐co‐EDMP‐PPV were 1.40–2.58 × 10⁵, and 1.19–1.52, respectively. Double‐layer light‐emitting diodes with the configuration of indium tin oxide/polymer/tris(8‐hydroxyquinoline)aluminum/Al devices were fabricated, and EDP‐co‐EDMP‐PPV (1:1) showed the highest EL performance and exhibited a maximum luminance of 1050 cd/m² at 19.5 V. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci 96: 1259–1266, 2005     

Synthesis of ω‐amino‐α‐phenylcarbonate alkanes and their polymerization to [n]‐polyurethanes

Aliphatic [n]‐polyurethanes have recently been synthesized from ω‐isocyanato‐α‐alkanols or, more traditionally, by cationic ring‐opening polymerization of cyclourethanes or by the Bu₂Sn(OMe)₂‐promoted polycondensation of ω‐hydroxy‐α‐O‐phenylurethane alkanes. For the latter procedures, the conditions employed do not seem to be suitable for highly functionalized monomers. In contrast, the polymerization of ω‐amino‐α‐phenylcarbonate alkanes is expected to occur under milder conditions. ω‐Amino‐α‐phenylcarbonate alkanes have been synthesized from 6‐aminohexanol (1) and 3‐aminopropanol (6). The procedure involves the N‐Boc protection of the amino group, followed by activation of the alcohol. Removal of the N‐Boc affords the corresponding ω‐amino‐1‐O‐phenyloxycarbonyloxyalkane hydrochlorides. Other oligomeric comonomers between 1 and 6 have been prepared. The polymerization of these precursors takes place in the absence of metal catalysts to afford the corresponding linear and regioregular [n]‐polyurethanes. The procedure described is useful for the preparation of stable ω‐amino‐α‐phenylcarbonate alkane derivatives, which possess varied chain lengths between the terminal functions. These monomers yield [n]‐polyurethanes having various structures starting from just two aminoalkanols. The polyurethanes were obtained in high yields, with reasonable molecular weight and polydispersity values, and they were characterized spectroscopically and thermally. These studies reveal constitutionally uniform structures that are free of carbonate or urea linkages. Copyright © 2010 Society of Chemical Industry     

Gold‐Catalyzed Synthesis of 3‐Acylimidazo[1,2‐a]pyridines via Carbene Oxidation

A convenient gold‐catalyzed strategy for the synthesis of imidazo[1,2‐a]pyridine derivatives has been developed via gold carbene complexes. This transformation opens a new synthetic route to a variety of 3‐carbonyl‐substituted imidazo[1,2‐a]pyridines using air as oxidant affording the products in good yields.

     

Synthesis,characterization and thermal degradation of poly[2‐(3‐p‐bromophenyl‐3‐methylcyclobutyl)‐2‐hydroxyethylmethacrylate]

In this work, 2‐(3‐p‐bromophenyl‐3‐methylcyclobutyl)‐2‐hydroxyethylmethacrylate (BPHEMA) [monomer] was synthesized by the addition of methacrylic acid to 1‐epoxyethyl‐3‐bromophenyl‐3‐methyl cyclobutane. The monomer and poly(BPHEMA) were characterized by FT‐IR and [¹H] and [¹³C]NMR. Average molecular weight, glass transition temperature, solubility parameter, and density of the polymer were also determined. Thermal degradation of poly[BPHEMA] was studied by thermogravimetry (TG), FT‐IR. Programmed heating was carried out at 10 °C min⁻¹ from room temperature to 500 °C. The partially degraded polymer was examined by FT‐IR spectroscopy. The degradation products were identified by using FT‐IR, [¹H] and [¹³C]NMR and GC‐MS techniques. Depolymerization is the main reaction in thermal degradation of the polymer up to about 300 °C. Percentage of the monomer in CRF (Cold Ring Fraction) was estimated at 33% in the peak area of the GC curve. Intramolecular cyclization and cyclic anhydride type structures were observed at temperatures above 300 °C. The liquid products of the degradation, formation of anhydride ring structures and mechanism of degradation are discussed. © 1999 Society of Chemical Industry     

Synthesis and spectroscopic characterisation of non‐aggregated novel axially 4‐{2‐[3‐(diethylamino)phenoxy]ethoxy} and crown ether substituted silicon phthalocyanines

This paper describes the synthesis and spectroscopic characterisation of a range of new axially disubstituted silicon phthalocyanines, with 4‐{2‐[3‐(diethylamino)phenoxy]ethoxy}, 4‐(1,4,7,10‐tetraoxacyclododecan‐2‐ylmethoxy) and 4‐(1,4,7,10,13,16‐hexaoxacyclooctadecan‐2‐ylmethoxy) groups as axial ligands. These axially disubstituted silicon phthalocyanine complexes were synthesised for the first time here. The newly synthesised silicon phthalocyanines were characterised by ultraviolet–visible, infrared, proton and carbon nuclear magnetic resonance spectroscopy, electrospray ionisation mass spectrometry and elemental analysis. The aggregation behaviour of these compounds was investigated in different concentrations of chloroform and the effects of various organic solvents on the absorption spectra were studied.     

Novel Aqueous Phase Supramolecular Synthesis of 3‐Pyrrolylindolin‐2‐ones and Pyrrolylindeno[1,2‐b]quinoxalines

Various 3‐pyrrolylindolin‐2‐ones and pyrrolylindeno[1,2‐b]quinoxaline were synthesized for the first time in high yields in water under neutral conditions by supramolecular catalysis involving β‐cyclodextrin. The β‐cyclodextrin can be recovered and reused a number of times without any loss of activity.     

8‐Benzyltetrahydropyrazino[2,1‐f]purinediones: Water‐Soluble Tricyclic Xanthine Derivatives as Multitarget Drugs for Neurodegenerative Diseases

8‐Benzyl‐substituted tetrahydropyrazino[2,1‐f]purinediones were designed as tricyclic xanthine derivatives containing a basic nitrogen atom in the tetrahydropyrazine ring to improve water solubility. A library of 69 derivatives was prepared and evaluated in radioligand binding studies at adenosine receptor (AR) subtypes and for their ability to inhibit monoamine oxidases (MAO). Potent dual‐target‐directed A₁/A_2A adenosine receptor antagonists were identified. Several compounds showed triple‐target inhibition; one of the best compounds was 8‐(2,4‐dichloro‐5‐fluorobenzyl)‐1,3‐dimethyl‐6,7,8,9‐tetrahydropyrazino[2,1‐f]purine‐2,4(1H,3H)‐dione ( 72 ) (human AR: K_i A₁ 217 nM , A_2A 233 nM ; IC₅₀ MAO‐B: 508 nM ). Dichlorinated compound 36 [8‐(3,4‐dichlorobenzyl)‐1,3‐dimethyl‐6,7,8,9‐tetrahydropyrazino[2,1‐f]purine‐2,4(1H,3H)‐dione] was found to be the best triple‐target drug in rat (K_i A₁ 351 nM , A_2A 322 nm; IC₅₀ MAO‐B: 260 nM ), and may serve as a useful tool for preclinical proof‐of‐principle studies. Compounds that act at multiple targets relevant for symptomatic as well as disease‐modifying treatment of neurodegenerative diseases are expected to show advantages over single‐target therapeutics.     

Direct Synthesis of 6‐Azabicyclo[3.2.1]oct‐6‐en‐2‐ones and Pyrrolizidines from Divinyl Ketones and Observation of Remarkable Substituent Effects

Substituents create access to molecular diversity. Under basic conditions, 6‐azabicyclo[3.2.1]oct‐6‐en‐2‐ones 3 and pyrrolizidines 4 are efficiently synthesized, respectively, in a single step from ethyl isocyanoacetate 2 and divinyl ketones 1 bearing an aryl or alkyl group at the 2‐position. For comparison, only the corresponding pyrrolizidines 4 ′ can be obtained from divinyl ketones 1 ′ bearing a methoxycarbonyl group at the 2‐position.     

Domino Reaction of Acyclic α,α‐Dialkenoylketene S,S‐Acetals and Diamines: Efficient Synthesis of Tetracyclic Thieno[2,3‐b]thiopyran‐Fused Imidazo[1,2‐a]pyridine/Pyrido[1,2‐a]pyrimidines

A series of unusual fused tetraheterocyclic compounds 3 , consisting of a thiopyran (ring A), a thiophene (ring B), a pyridine (ring C), and an imidazole or a pyrimidine (ring D) core, with a bridgehead nitrogen and an angular methyl group, were successfully synthesized by a catalyst‐free, one‐pot, two‐component domino reaction of 4‐(4‐methyl‐1,3‐dithiol‐2‐ylidene)‐1,7‐bis(aryl/heteroaryl)hepta‐1,6‐diene‐3,5‐dione 2 and diamines. In this reaction, up to five new bonds were formed accompanied by the C S bond cleavage of the 1,3‐dithiole ring of 2 , with water as the only by‐product.