Synthesis of 2,3-Dihydrothiopyran-4-ones from 3-Oxo-1-pentene-4-ynes

Summary. 3-Oxo-1-pentene-4-ynes were converted with sodium sulfide or hydrogensulfide to give 2,6-disubstituted 2,3-dihydrothiopyran-4-one derivatives. The starting materials were prepared in two steps from terminal alkynes and α,β-unsaturated aldehydes.     

An Easy Synthesis of Pyranopyrimidines

Summary.  The one-pot reaction of valerolactone with nitriles in the presence of triflic anhydride affords 2,4-disubstituted pyrano[2,3-d]pyrimidines. Subsequent addition of methyl thiocyanate leads to 2,4-bis(methylthio)pyranopyrimidines which can easily be converted into the corresponding methylsulfonyl derivatives. The reaction of these derivatives with different nucleophiles produces a variety of substituted pyranopyrimidines.     

The Behaviour of Nitrilimines Towards Ethyl Isocyanoacetate

Summary.  Interactions between nitrilimines and the title isocyanide afford, through two competing pathways, 2,3-dihydro-1,2,4-triazines and 1,3-oxazoles. In situ cycloaddition of unreacted nitrilimine with the triazines gives rise to a third class of products, the bicyclic 1,5,6,8a-tetrahydro[1,2,4]triazolo[4,3-d][1,2,4]triazines. Acceptor-free representatives of the latter are prone to triazine ring cleavage, yielding triazolyl ketone hydrazones which served as a structure proof. Substituent effects became apparent upon employment of N-(4-methoxyphenyl)- and N-(4-nitrophenyl)nitrilimines: whereas the former afforded a quinoxaline as the fourth product, triazine formation was totally blocked with the latter, the corresponding oxazole being the sole product. The constitution of acceptor-substituted bicyclic compounds (which failed to give the structure-revealing hydrazones) was established by an X-ray diffraction analysis. Corresponding author. E-mail: d.moderhack@tu-bs.de Received March 5, 2002; accepted March 19, 2002     

The Reaction of Cyclic Nitroenamines with Isocyanates. Synthesis of 1,6-Polymethylene-6-nitromethyl-1,3,5-triazine-2,4-dione Derivatives

Summary. The reactions of cyclic nitroenamines with isocyanates were investigated. It was found that two different products could be obtained: in inert media -carbamoyl products were observed and when a strong base was used 1,6-polymethylene-6-nitromethyl-1,3,5-triazine-2,4-dione derivatives were isolated.     

Antimicrobial Activity and Structural Study of Disubstituted Thiourea Derivatives

Summary. The antimicrobial activity of six N-phenyl- and fourteen N-benzoylthiourea derivatives were evaluated from their Minimal Inhibitory Concentration (MIC) values using the microdilution procedure against ten microorganisms. Most of the compounds exhibited selective activity against fungi and Gram-positive bacteria, which were very effectively inhibited by some of the tested thioureas. Additionally, SAR considerations and four novel X-ray diffraction structures of N-benzoylthioureas are included.     

Synthesis of new polyhalogenoalkyl-containing phosphonates with an enaminone core and their use in the preparation of fluorinated heterocycles

A number of polyhalogenoalkyl-containing phosphonates with an enaminone core were synthesized from readily available β-alkoxyvinyl polyhalogenoalkyl ketones by successive bromination, amination, and Arbuzov reaction. The new phosphonates were used for the syntheses of five- and six-membered heterocycles bearing both trifluoromethyl and methylenephosphonate groups.     

One-pot cyclization of dilithiated nitriles with isothiocyanates and epibromohydrin. Synthesis of 2-cyano-1-(hydroxymethyl)cyclopropanes and 2-cyanomethylidene-4-(hydroxymethyl)thiazolidines

The cyclization of dilithiated nitriles with epibromohydrin afforded 2-cyano-1-(hydroxymethyl)cyclopropanes. 2-Cyanomethylidene-(4-hydroxymethyl)thiazolidines were prepared by one-pot cyclization of dilithiated nitriles with isothiocyanates and epibromohydrin.     

Synthesis of thiohydantoins under one-pot three-component solvent-free conditions

A direct and efficient one-pot three-component synthesis protocol was developed for the synthesis of thiohydantoins from readily and widely available substrates (isothiocyanates, ethyl chloroacetate, and amines) employing solvent-free conditions. Correspondence: Song Cao, Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China.     

A Convenient Mannich-Type One-Pot Synthesis of Pyrimido[6,1-b][1,3,5]thiadiazines

Summary. 3-(Het)aryl-2-cyanoprop-2-enethioamides easily reacted with primary amines and excessive formaldehyde under mild conditions to afford pyrimido[6,1-b][1,3,5]thiadiazine derivatives in moderate yields. Furthermore, 2-cyano-2-cyclohexylideneethanethioamide reacted in the similar Mannich-type manner to give spiro-conjugated pyrimido-1,3,5-thiadiazines. The structure of 3,7-dibenzyl-8-(fur-2-yl)-3,4,7,8-tetrahydro-2H,6H-pyrimido[6,1-b][1,3,5]thiadiazine-9-carbonitrile was determined by X-ray diffraction analysis.     

Reaction of methyl (2E)-3-dimethylamino-2-(1H-indol-3-yl)-propenoate with ureas: facile entry into the polycyclic meridianin analogues with uracil structural unit

Methyl (2E)-3-dimethylamino-2-(1H-indol-3-yl)-propenoate was prepared simply and efficiently in two steps from 3-indoleacetic acid employing N,N-dimethylformamide dimethylacetal (DMFDMA). Upon treatment of (2E)-3-dimethylamino-2-(1H-indol-3-yl)-propenoate with various (thio)ureas in the presence of an acid 2-(1H-indol-3-yl)-3-(3-substituted(thio)ureido)propenoates were obtained in high yields. A base promoted cyclization of these (thio)ureidopropenoate derivatives afforded 5-(indol-3-yl)-3-substituted-pyrimidine-2,4-diones which represent a new family of meridianine analogues.     

Synthesis of heterospiranes by cyclization of dinucleophiles with 1,1-bis(tosyloxymethyl)cyclopropane and -cyclobutane

A variety of heterocyclic spiranes were prepared by cyclization of dinucleophiles with 1,1-bis(tosyloxymethyl)cyclopropane and -cyclobutane.     

Visible Light-Mediated Cyclisation Reaction for the Synthesis of Highly-Substituted Tetrahydroquinolines and Quinolines

Condensation of 2-vinylanilines and conjugated aldehydes followed by an efficient light-mediated cyclisation selectively yields either substituted tetrahydroquinolines with typically high dr, or in the presence of an iridium photocatalyst the synthesis of quinoline derivatives is demonstrated. These atom economical processes require mild conditions, with the substrate scope demonstrating excellent site selectivity and functional group tolerance, including azaarene-bearing substrates. A thorough experimental mechanistic investigation explores multiple pathways and the key role that imine and iminium intermediates play in the absorption of visible light to generate reactive excited states. The synthetic utility of the reactions is demonstrated on gram scale quantities in both batch and flow, alongside further manipulation of the medicinally relevant products.     

A Novel Domino Reaction: Cyclization of Alkynyl Sulfides by Reaction with IPy2BF4

Formation of polycyclic structures within a few minutes: The intramolecular cyclization of diynes, activated by a benzenesulfenyl substituent, upon reaction with IPy₂BF₄ proceeds as an efficient exo–endo coupling. A subsequent novel Friedel–Crafts-like ring closure provides the product [Eq. (1)]. Thus, intra- and intermolecular cyclizations can be carried out.     

Synthesis of Pyrrolo[2,1-<Emphasis Type="Italic">b</Emphasis>]thiazol-3-one Derivatives

Summary. Ethyl [4-oxo-3-(2-oxo-2-arylethyl)thiazolidin-2-ylidene]acetates and [4-oxo-3-(2-oxo-2-arylethyl)thiazolidin-2-ylidene]acetonitriles were shown to react with substituted benzaldehydes at the endocyclic methylene group leading to the corresponding 5-arylmethylidene derivatives. Their treatment with DMF · POCl₃ complex yielded 3-oxo-5-aroyl-2-arylmethylidene-2,3-dihydropyrrolo[2,1-b]thiazole-7-carboxylic acids ethyl esters and -7-carbonitriles. The structures of the pyrrolothiazoles were confirmed by an X-ray crystallographic study, which indicated the (Z)-configuration at the arylmethylidene moiety.     

An Efficient <Emphasis Type="Italic">Mannich</Emphasis>-Type One-Pot Synthesis of 3,5,7,11-Tetraazatricyclo [7.3.1.0<Superscript>2,7</Superscript>]tridec-2-ene Derivatives Starting from Functionalized 1,4-Dihydropyridines

Summary. 3,5,7,11-Tetraazatricyclo[7.3.1.0^2,7]tridec-2-ene derivatives were prepared in one-pot manner from N-methylmorpholinium 6-amino-3,5-dicyano-4-spiro(1′-cycloalkane)-1,4-dihydropyridine-2-thiolates, primary amines, and formaldehyde in 70–88% yields. The structure of 5,11-dibenzyl-13-spiro(1′-cyclopentane)-8-thioxo-3,5,7,11-tetraazatricyclo[7.3.1.0^2,7]tridec-2-ene-1,9-dicarbonitrile was determined by X-ray diffraction analysis.     

Synthesis of 7-arylquinolinones and 6-arylindoles from 3-aminobiphenyls through regioselective cyclization reactions

7-Arylquinolinones were obtained in two steps from 3-aminobiphenyls through conversion into cinnamic amides. The highly regioselective cyclization under elimination of anisole proceeded in the presence of phosphoric acid and phosphorous pentoxide. 6-Arylindoles were accessible, although in lower yields, from 3-aminobiphenyls via 3-(biphenylamino)acrylates and palladium-catalyzed cyclization reactions.     

4-Aminobicyclo[2.2.2]octanone Derivatives with Antiprotozoal Activities

Summary.  4-Aminobicyclo[2.2.2]octanones which were prepared in one-pot-reactions from benzylidene acetone and dialkylammonium rhodanides were reduced stereoselectively to their corresponding alcohols. The activities of the bicyclic compounds against causative organisms of tropical deseases were examined. The 4-aminobicyclo[2.2.2]octan-2-ols were in general more active against Trypanosoma b. rhodesiense and Plasmodium falciparum than the corresponding keto compounds. Corresponding author. E-mail: robert.weis@uni-graz.at Received November 27, 2002; accepted December 2, 2002 Published online May 2, 2003     

Structural and Quantitative Analyses of 4-Chloroaniline-Derived Oligomers

Abstract

The oxidation of 4-chloroaniline by a peroxidase resulted in eight oligomeric products. A reverse-phase high performance liquid chromatography (HPLC) method was developed so that substrate disappearance and the corresponding product formations could be quantitatively monitored. The product mixture was isolated from the aqueous reaction solution with solid-phase extraction and the extract components were separated by thin-layer chromatography (TLC). The individual TLC bands were extracted for mass spectrometric and proton nuclear magnetic resonance analyses. The product mixture was found to contain dimers, trimers, and tetramers with benzoquinone monoimine, benzopuinone di-mine, diaminobenzene, and azobenzene structures. Analytical methodologies were specific for the study of the oxidative transformation of 4-chloroaniline, but they should be applicable to other anilinederived oligomers.     

Synthesis, NMR and X-ray characterisation of 6-substituted 4-amino-5-aryldiazenyl-1-arylpyridazinium salts

A new simple method has been used to prepare 6-substituted 4-(subst. amino)-5-aryldiazenyl-1-arylpyridazinium salts from N-methyl- or N-aryl-3-amino-1-phenylbut-2-en-1-ones and 4-aminopent-3-en-2-ones and substituted benzenediazonium tetrafluoroborates or hexafluorophosphates. The structure of selected derivatives was studied by means of ¹⁵N NMR spectra and X-ray.     

Synthesis of 7,8-benzo-9-aza-4-oxabicyclo[3.3.1]nonan-3-ones by sequential ‘condensation–iodolactonization’ reactions of 1,1-bis(trimethylsilyloxy)ketene acetals with isoquinolines

Functionalized 7,8-benzo-9-aza-4-oxabicyclo[3.3.1]nonan-3-ones were prepared by regio- and diastereoselective condensation of 1,1-bis(silyloxy)ketene acetals with isoquinolinium salts and subsequent regioselective and stereospecific iodolactonization.