Studies on the Chemistry of Thienoannelated O , N - and S , N -Containing Heterocycles, 28 [1]. Synthesis of Imidazo[1,5- d ]thieno[2,3- b ][1,4]thiazine Derivatives as GABA -Receptor Ligands

Summary.  GABA-receptor-ligands are still very interesting in drug-development. Usually benzodiazepines are used in the treatment but they have serious side-effects. Thus, a recently synthesized quioxaline derivative which showed reduced side-effects in an animal model was used as a model-substance. The cyclus was modified to optimize the pharmacological profile. Accordingly, a series of imidazo-thieno-thiazines was synthesized starting from 5-acetyl-2-chloro-3-nitrothiophene to yield 6-ethyl-2,3-dihydro-1H-thieno[2,3-b][1,4]thiazine-2-one. Reaction with potassium tert-butoxide and diethylchlorophosphate gave an intermediate, which resulted in the desired ring system after adding the corresponding isocyanides and potassium tert-butoxide. Corresponding author. E-mail: thomas.erker@univie.ac.at Received August 6, 2002; accepted August 13, 2002     

Synthesis of stable azomethine ylides by the rearrangement of 1,3-dipolar cycloadducts of 3,4-dihydroisoquinoline-2-oxides with DMAD

1-Aryl-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinolines were prepared according to a one-pot procedure involving the reaction of 2-(3,4-dimethoxyphenyl)-ethylamine with aromatic aldehydes in TFA at reflux. The tetrahydroisoquinolines were treated with H₂O₂-WO₄²⁻ in methanol at room temperature to give the corresponding 3,4-dihydroisoquinoline-2-oxides. Treatment of these cyclic nitrones with DMAD in toluene at room temperature gave the corresponding isoxazolo[3,2-a]isoquinolines. These compounds were heated in toluene at reflux to give the corresponding ylides in high yields (Method A). The effect of the substituents on the rate of the rearrangement of such compounds prompted us to discuss a new mechanism involving consecutive C-C bond heterolysis and 1,3-sigmatropic shift. A one-pot reaction involving the treatment of the nitrones with equimolar amounts of DMAD in refluxing toluene also gave the ylides (Method B). The structures of the prepared compounds were elucidated by spectral means and elemental analyses.     

A novel and direct synthesis of chroman derivatives using a hypervalent iodine(III) reagent

The direct aromatic carbon-oxygen bond-formation reaction was described and the novel and simple synthetic method for chroman derivatives involving aromatic cation radical intermediates was developed using the hypervalent iodine(III) reagent, phenyliodine(III) bis(trifluoroacetate) (PIFA).     

Synthesis of novel poly(ethylene glycol) supported benzazepines: the crucial role of PEG on the selectivity of an intramolecular Heck reaction

Poly(ethylene glycol) (PEG 3400) was used as a soluble polymeric support for the synthesis of a series of novel benzazepines. The key step for the preparation of these heterocycles was a phosphine-free palladium-catalyzed Heck reaction. Palladium nanoparticles formed during the course of the reaction were characterized. The presence of PEG 3400 influenced the outcome of the reaction in terms of selectivity.     

An improved cyclization protocol for the synthesis of diazabicyclo[4.3.0]alkanes

We have recently described the synthesis of diazabicyclo[4.X.0]alkanes and their use as ligands for the prostate specific membrane antigene (PSMA). The key step of our synthetic route toward these diazabicycloalkanes is an oxidative cleavage of a bicyclic diol moiety followed by the attack of a nitrogen nucleophile to the resulting intermediate bisaldehyde. We herein describe the mechanism of this ring closure and its stereochemical consequences. In addition, we report a convenient method for trapping intermediate bisaldehydes by Wittig reagents. This trapping allows the synthesis of 3,5-disubstituted proline derivatives, which are shown to be versatile precursors for functionalized diazabicycloalkane dipeptide mimetics.     

Transformation of acridines and azepines into the corresponding 3-oxo-heterocycles by means of hypervalent aromatic iodine compounds

Summary The acridines3,5, and6, as well as the dibenzo[b,f]-azepine4 were converted into the 3-oxo-derivatives7–10 using hypervalent iodine compounds (iodosylbenzene and bis-(trifluoroacetoxy)iodopentafluorobenzene).

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Oxidation von Acridinen und Azepinen in ihre 3-Oxoderivate mit Hilfe von hypervalenten aromatischen Jodverbindungen (Kurze Mitt.)

Zusammenfassung Die Acridine3,5 und6 sowie das Dibenzo[b,f]azepin4 wurden mit Hilfe der beiden hypervalenten Jod-Verbindungen Jodosobenzol (1) und Bis-trifluoroacetoxyiodbenzol (2) zu den entsprechenden 3-Acridinonen7,9 und10 sowie zum Dibenzoazepin-3-on8 oxidiert.

     

Synthesis of Pyrimidine Annelated Heterocycles [1]. Regioselective Heterocyclization of 6-Cyclopent-2-enyl-5-hydroxy-1,3-dimethyl-pyrimidine-2,4( 1H, 3H)-dione and 5-Cyclopent-2-enyl-6-hydroxy-1,3-dimethylpyrimidine-2,4( 1H, 3H)-dione

Summary. Two hitherto unreported pyrimidine annelated heterocycles were synthesized from 6-cyclopent-2-enyl-5-hydroxy-1,3-dimethylpyrimidine-2,4(1H,3H)-dione and 5-cyclopent-2-enyl-6-hydroxy-1,3-dimethylpyrimidine-2,4(1H,3H)-dione by reaction with pyridine hydrotribromide or hexamethylenetetramine hydrotribromide. The first one was also obtained by reaction with concentrated sulfuric acid.Received October 28, 2002; accepted October 30, 2002 Published online June 2, 2003     

Phosphaalkynes—Syntheses,Reactions, Coordination Behavior [New Synthetic Methods (73)]

Organophosphorus compounds have been applied in two ways in chemical synthesis. They can either be used as a reagent in a step of the synthesis (for example, in the Wittig reaction) or they can be incorporated directly into the target molecule. This second application, in particular, has expanded greatly in the last few years with the preparation of low-coordination phosphorus compounds. These include the phosphaalkynes, which are of great interest to organic and inorganic chemists. Phosphaalkynes have been employed in the synthesis of heterocyclic compounds, phosphaarenes and their valence isomers, and polycyclic compounds. Further applications have been the use of phosphaalkynes as new ligand systems in complex chemistry and their cyclooligomerization with organometallic reagents. While the chemical properties of phosphaalkynes have little in common with those of nitriles, they are in many ways very similar to those of the isoelectronic acetylenes.     

Iminophosphanes: Unconventional Compounds of Main Group Elements

The large number of known stable compounds in which phosphorus has a low coordination number makes it clear that such compounds can no longer be regarded as “exotic” in main group chemistry. While the rich chemistry of P? C multiply bonded systems makes clear their affinity to their organic congeners, iminophosphanes in particular are also of increasing importance. The linkage of a phosphinidine fragment with an imine fragment via a multiple bond gives rise to a class of compounds with an unusually wide range of structural types. This in turn leads to a broad spectrum of chemical behavior which makes iminophosphanes extremely useful synthetic building blocks in organoelement chemistry.     

Gas-phase thermolysis of condensed-1,2,4-triazines: interesting routes toward heterocyclic ring systems

Gas-phase thermolysis of thieno[2,3-e][1,2,4]triazines gave benzonitrile, isothiazole, pyridazine, and thieno[2,3-d]thiazole derivatives. Similar transformation of benzo[1,2,4]triazine and phenanthro[9,10-e][1,2,4]triazine derivatives into their corresponding condensed thiazoles has been achieved by heating at 350 °C with sulfur. A mechanism for these pyrolytic transformations was proposed.