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 a New Series of Imidazo-[1,5-a]pyrido[2,3-e]pyrazines as Potential Ligands for the GABA Receptor Complex

Summary.  Starting from 2-chloro-3-nitropyridine, 2-isopropyl-1,4-dihydropyrido[2,3-b]pyrazin-2(3H),3-dione was synthesized. This compound was reacted with potassium tert-butoxide and diethyl chlorophosphate to afford an intermediate dihydropyrido[2,3-b]pyrazin-2-ylphosphate derivative which in turn furnished the desired 1,2,4-oxadiazolylimidazo[1,5-a]pyrido[2,3-e]pyrazine derivatives with 5-alkyl-3-isocyanomethyl-1,2,4-oxadiazoles in the presence of additional tert-butoxide. The title compounds are potential ligands for the γ-aminobutyric acid A/benzodiazepine receptor complex. Received November 26, 2001. Accepted December 3, 2001     

Synthesis of a New Series of Imidazo[1,5- d ]pyrido[2,3- b ][1,4]thiazines as Potential Ligands for the GABA Receptor Complex

 Starting from 2-chloro-3-nitropyridine, 1H-pyrido[2,3-b][1,4]thiazin-2(3H)-one was synthesized. This compound was reacted with potassium tert-butoxide and diethyl chlorophosphate to give the intermediate 1H-pyrido[2,3-b][1,4]thiazin-2-ylphosphate derivative, which in turn afforded the 1,2,4-oxadiazolylimidazo[1,5-d]pyrido[2,3-b]pyrazine derivatives. The title compounds are potential ligands for the γ-aminobutyric acid A/benzodiazepine receptor complex.     

Synthesis of a New Series of Imidazo[1,5-d]pyrido[2,3-b][1,4]thiazines as Potential Ligands for the GABA Receptor Complex

Summary.  Starting from 2-chloro-3-nitropyridine, 1H-pyrido[2,3-b][1,4]thiazin-2(3H)-one was synthesized. This compound was reacted with potassium tert-butoxide and diethyl chlorophosphate to give the intermediate 1H-pyrido[2,3-b][1,4]thiazin-2-ylphosphate derivative, which in turn afforded the 1,2,4-oxadiazolylimidazo[1,5-d]pyrido[2,3-b]pyrazine derivatives. The title compounds are potential ligands for the γ-aminobutyric acid A/benzodiazepine receptor complex. Corresponding author. E-mail: thomas.erker@univie.ac.at Received February 22, 2002. Accepted March 6, 2002     

Research on nitrogen containing heterocyclic compounds. XIX: Synthesis of 8H-imidazo[2,1-c]-s-triazolo[4,3-a]-[1,4]benzodiazepine and its 1-derivatives

Reaction of 2-nitrobenzyl iodide with 1H-imidazole, in the presence of potassium tert-butoxide and 18-crown-6, gave 1-(2-nitrobenzyl)-1H-imidazole. Trichloroacetylation of this compound furnished trichloroacet-ylimidazole 8 , which on treatment with sodium ethoxide was transformed into the corresponding ethoxycarbonyl derivative 9 . Catalytic reduction of the nitro group to the amino group yielded 10 , which was then cyclized to 10,11-dihydro-11-oxo-5H-imidazo[2,1-c][1,4]benzodiazepine 11. Treatment of this lactam with di-4-morpholinylphosphinic chloride followed by reaction of the intermediate 12 with formylhydrazine gave the title compound or its 1-derivatives when acetylhydrazine or isonicotinoylhydrazine were used instead of formylhydrazine.     

Syntheses of (E)- and (Z)-3-styrylchromones

Several (E)- and (Z)-3-styrylchromones were prepared by two different methodologies, the Wittig reaction of chromone-3-carboxaldehyde with benzylic ylides and the Knoevenagel condensation of chromone-3-carboxaldehyde with phenylacetic acids in the presence of potassium tert-butoxide under microwave irradiation. The Knoevenagel reaction followed by a decarboxylation offered an efficient and diastereoselective method for preparing (E)-3-styrylchromones in a shorter reaction time. It was also demonstrated that phenylacetic acid can also be substituted with success by phenylmalonic acid. The stereochemistry of all products was assigned by NMR experiments.     

Studies on the chemistry of thienoannelated O,N‐ and S,N‐containing heterocycles. 24 [1]. Synthesis of imidazo[1,5‐d]thieno[2,3‐b][1,4]‐thiazine derivatives as potential receptor ligands

A facile synthesis of the imidazo[1,5‐d]thieno[2,3‐b][1,4]thiazine ring system is described. Reaction of 6‐benzyl‐2,3‐dihydro‐1H‐thieno[2,3‐b][1,4]thiazine‐2‐one ( 1 ) with potassium tert‐butoxide and diethylchlorophosphate gave intermediate 2 which resulted in the disired ring system after adding the corresponding isocyanides and potassium tert‐butoxide.     

A One-Pot Procedure for Thieno[2,3-b]thiophene and Some of its Derivatives Using Derivatives of 1,3-Pentadiyne and Carbon Disulfide as Building Units

Thieno[2,3-b]thiophene and its 2-methyl- and 2-N,N-dialkylamino derivatives have been obtained in fair yields in a one-pot procedure using the diynes CH₃C≡CC≡CR (R=Me₃Si, CH₃, NMe₂, NEt₂) and carbon disulfide as building blocks and n-butyllithium, potassium tert-butoxide and t-butylacohol as reagents.     

Synthesis of derivatives of a new heterocyclic system pyrazolo[3,4-b]pyrido[1′,2′: 1,2]imidazo[4,5-d]pyridine

1-[4-Aminoarylpyrazolo[3,4-b]pyridin-5-yl]pyridinium chlorides undergo cyclization under reflux in tert-butanol in the presence of an excess of potassium tert-butoxide to form tetracyclic derivatives of pyrazolo[3,4-b]pyrido[1′,2′:1,2]imidazo[4,5-d]pyridine. The reaction scheme of the processes is proposed. The structures of the reaction products were confirmed by physicochemical methods. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 4, pp. 710–714, April, 2006.     

1-(Triphenylmethyl)allyl potassium :conformational preference and [1,2]-rearrangement

Upon treatment with the superbasic 1 : 1 mixture of butyllithium and potassium tert-butoxide cis- and trans-1,1,1-triphenyl-2-butene as well as 4,4,4-triphenyl-1-butene undergo a hydrogen/metal exchange to afford 1-(triphenylmethyl)allyl potassium [4,4,4-triphenyl-2-butenyl potassium] which can exist in two stereoisomeric forms. Torsional equilibration leads to an endo/exo-ratio of approximately 50 : 50. Novel endo-stabilizing interactions are discussed to rationalize this result. At temperatures around or above 0°C a phenyl 1,2-migration, though no 1,4-migration takes place.     

C2 molecule: formation from bromoacetylene and reactions with cyclohexene or 2,3-dimethyl-2-butene

The C₂ molecule (1,2-ethynediyl) has been prepared by dehydrohalogenation of 1,2-dibromoethylene with an excess of potassium tert-butoxide in 2,3-dimethyl-2-butene as the solvent and the reagent. The major products of this reaction were 2,3-dimethylbut-3-en-2-ol and dibromoacetylene.     

A facile one-pot synthesis of 6,7,8,9-tetrahydrobenzo[4,5]thieno[2,3-d]-1,2,4-triazolo[4,5-a]pyrimidin-5-ones

Abstract  

The reaction of 2-mercapto-6,7,8,9-tetrahydro-3H-benzo[4,5]thieno[2,3-d]pyrimidin-4-one or its 2-methylthio derivative with hydrazonoyl halides, in the presence of triethylamine, yielded 6,7,8,9-tetrahydrobenzo[4,5]thieno[2,3-d]-1,2,4-triazolo[4,5-a]pyrimidin-5-ones. The structure of the latter compounds was further confirmed by reaction of 2-mercapto-6,7,8,9-tetrahydro-3H-benzo[4,5]thieno[2,3-d]pyrimidin-4-one with the appropriate active chloromethylenes followed by coupling of the products with benzenediazonium chloride to afford the non-isolable azo-coupling products which converted, in situ, to 6,7,8,9-tetrahydrobenzo[4,5]thieno[2,3-d]-1,2,4-triazolo[4,5-a]pyrimidin-5-ones. The reaction mechanism was proposed and the products were screened for their biological activity. Some of the newly synthesized compounds had a moderate effect against some bacterial and fungal species.     

Heterocycles with a Benzothiadiazeypine Moiety. I. Synthesis of Pyrrolo[1,2-b]-s-triazolo[3,4-d] [1,2,5]benzothiadiazepine 5,5-Dioxide

Condensation of 2-nitrobenzenesulfonyl chloride with 2-ethoxycarbonyl-1H-pyrrole in the presence of potassium tert-butoxide and 18-crown-6 furnished 2-ethoxycarbonyl-1-(2-nitrobenzenesulfonyl)-1H-pyrrole. Reduction of nitro group to amino and subsequent cyclization by heating the aminoester in the presence of 2-hydroxypyridine as a bifuctional catalyst led to 11-oxo(10H)-pyrrolo[1,2-b] [1,2,5]benzothiadiazepine 5,5-dioxide. Treatment of the latter compound with di-4-morpholinylphosphinic chloride gave the corresponding phosphinyloxyimine, which on reacting with formylhydrazine underwent intramolecular cyclization to afford the title tetracyclic ring.     

Tetrazoles: XLVI. 3H-1,3,4-Benzo- and Pyrido[6,7-b][1,3,4]triazepines from 5-Aryltetrazoles. Synthesis and Chemical Properties

2,5-Disubstituted 3H-1,3,4-benzotriazepines were synthesized by heating of N-imidoyltetrazoles in toluene at 110°C. Alkylation of these compounds, as well as of 3H-pyrido[6,7-b][1,3,4]triazepines with alkyl halides in THF in the presence of potassium tert-butoxide gave the corresponding 1-alkyl derivatives in good yield and with high regioselectivity.     

Synthesis of 2,7-disubstituted-5,6-dimethylpyrrolo-[2,3-d]-1,3-oxazin-4-ones as antifungal agents

A series of novel 5,6-dimethylpyrrolo[2,3-d]-1,3-oxazin-4-ones were synthesized from 2-amino-3-tert-butoxy-carbonyl-4,5-dimethylpyrroles. Two methods were used, cyclodehydration of 2-acylamino-3-carboxypyrroles with acetic anhydride and direct conversion of the 5,6-dimethylpyrrolo[2,3-d]-1,3-oxazin-2,4-diones to the title compounds with an anhydride directly providing the 2 substituent. Molecular modeling techniques revealed that these pyrrolo[2,3-d]oxazinones were rigid analogues of the allylamine antifungals. The compounds were tested for in vitro activity against Tricophyton and Scopulariopsis sp.     

Complete regioselective formation of 2-(arylsulfinyl)diphenyl sulfides from 5-arylthianthreniumyl perchlorates

Treatment of 5-arylthianthreniurnyl perchlorates with potassium tert-butoxide in dimethyl sulfoxide at room temperature gave 2-(arylsulfinyl)diphenyl sulfides (29–79% yields), which are the first examples for complete regioselective formation of S-monoxides from unsymmetrical arylthiodiphenyl sulfides.     

Synthesis,structures, and selected chemical properties of 2-chloro- and 2-bromo-1,1-diferrocenylcyclopropanes

2-Chloro- and 2-bromo-1,1-diferrocenylcyclopropanes were synthesized as Z- and E-isomers with respect to the ferrocenyl substituent having a bisector orientation. The structure of Z-2-chloro-1,1-diferrocenylcyclopropane was confirmed by X-ray diffraction analysis. Treatment of the resulting monohalides with potassium tert-butoxide in dimethyl sulfoxide afforded 3,3-diferrocenylcyclopropene in 20% yield. The small ring in halogen-substituted diferrocenylcyclopropanes and diferrocenylcyclopropene is readily cleaved to give predominantly 3-ferrocenyl-1H-cyclopentaferrocene.     

Substituted pyridine coordinated N,N-trans and N,N-cis cyclopalladated complexes of (S)-4-tert-butyl-2-phenyl-2-oxazoline: Crystal structures, spectral study and catalysis of the decomposition of PS pesticides

Three pyridine coordinated cyclopalladated complexes: (S)-chloro{2-[2-(4-tert-butyl)oxazolinyl]phenyl-C,N}(4-R-pyridine)palladium(II) (R = H, 2; R = CF₃, 3; R = NMe₂, 4), have been synthesized and structurally characterized. While the crystal structure shows that 2 has a normal N,N-trans-conformation in the coordination sphere of palladium(II), 3 and 4 exhibit uncommon N,N-cis-conformations. From ¹H NMR measurements, the major coordination isomer in deuterated chloroform solution is N,N-trans configuration for three palladacycles. It was found that the three complexes catalyze effectively the methanolysis of the PS pesticides including chiral thiophosphates but show different activity depending on the substituents of co-coordinated pyridine ring in 2–4.     

Intramolecular Cyclization of Furfuryl 2-Propynyl Ether

Intramolecular cyclization of furfuryl 2-propynyl ether in the presence of a catalytic amount ofpotassium tert-butoxide in tert-butyl alcohol gives 3a'6-epoxy-1'3-dihydro-6H-isobenzofuran. The cyclizationis presumed to be favored by preliminary isomerization of the 2-propynyl group into allenyl. Heating of thecyclization product with excess potassium tert-butoxide in tert-butyl alcohol results in cleavage of the epoxybridge with formation of 6-hydroxy-1'3-dihydroisobenzofuran.     

Procedure for the Rapid Synthesis of the Monomer 1,4-Bis(chloromethyl)-2-(2-ethylhexyloxy)-5-methoxybenzene

The alkylation of 4-methoxyphenol with 2-ethylhexyl bromide was accelerated by using potassium tert-butoxide in dimethylformamide. Subsequent chloromethylation occurred quickly using acetic acid as a cosolvent to give the poly[(2-(2-ethylhexyloxy)-5-methoxy-p-phenylene)vinylene] (MEH-PPV) monomer in 61% overall yield on a 2-mol scale.