Jan Světlík

Oxygen-bridged tetrahydropyridines, hexahydropyridines, and dihydropyridones via a Hantzsch-like synthesis with 4-(2-hydroxyphenyl)but-3-en-2-one

Substituted oxygen-bridged tetrahydro-2-pyridones and tetrahydropyridines (4) and (7) were synthesized by condensation of 4-(2-hydroxyphenyl)but-3-en-2-one (1) with Meldrums acid (2) and 3-aminocrotononitrile, respectively, in the presence of ammonium acetate. Analogous cyclo-condensations of (1) with methyl 3-amino-2,4-dicyanobut-2-enoate (8) and methyl 3-amino-2-cyanopentene-2-dioate (10) led to oxygen-bridged hexahydropyridines (9) and (11), respectively, of different stereochemistry in the piperidine rings. The dichotomy in the stereospecific routes to these oxygen-bridged heterocycles is discussed. Preparation of 4-aryl substituted dihydro-2-pyridones is also reported.

Formation of oxygen-bridged heterocycles in the hantzsch synthesis with 4-(2-hydroxyphenyl)but-3-en-2-one

Condensations of 4-(2-hydroxyphenyl)but-3-2-one with methyl acetoacetate, pentane-2,4-dione, dimedone, and methyl cyanoacetate under the conditions of the Hantzsch synthesis lead to 9-methyl-8-oxa-10-azatricyclo[7.3.1.02,7]trideca-2,4,6,11-tetraene derivatives and related heterocycles. An analogous condensation with 2-aminopropene-1,1,3-triscarbonitrile yields stereoselectively 11-dicyanomethylene-9-methyl-8-oxa-10-azatricyclo[7.3.1.02,7]trideca-2,4,6-triene-12α-carbonitrile. Under suitable reaction conditions, the condensation of 4-(2-hydroxyphenyl)but-3-en-2-one with cyanamide affords various products with the 9-methyl-8-oxa-10,12-diazatricyclo[7.3.1.02,7]trideca-2,4,6,11-tetraene skeleton. Condensation products of salicylaldehyde with acetone, 2-aminopropene-1,1,3-triscarbonitrile, and 3-aminocrotononitrile have been identified.

13C-NMR of substituted tetrazoles

Inductive and resonance effects of phenyl substituted tetrazoles from13C NMR studies are calculated.13C NMR shifts of a series of these compounds is reported and the aminotetrazole—iminotetrazoline tautomerism of the compounds studied is discussed.ZusammenfassungAus13C-NMR-Daten werden induktive und Resonanzeffekte von phenylsubstituierten Tetrazolen berechnet. Es werden13C-NMR-Verschiebungen einer Reihe dieser Verbindungen angegeben und die Aminotetrazol—Iminotetrazolin-Tautomerie diskutiert.

Synthesis of 2-Chloromethyl-1,4-Dihydropyridines

Abstract The title compounds were prepared by condensation of aldehydes with alkyl 3-aminocrotonate and 4-chloroacetoacetate.

Unusual course of condensation of 2-bromo-1 phenylethylidenemalononitrile with substitued thioureas

Abstract Condensation of the title compound with 2-mercapto-4,5-dihydroimidazole yields a substituted pyrrolo [ 1,2-a ] imidazole. The reaction with 2-mercapto-3,4,5,6-tetrahydropyrimidine gives an isothiocyanate due to opening of the heterocyclic ring.

DMSA and its complexes with radioisotopes: review

Meso-2,3-dimercaptosuccinic acid (DMSA) forms stable complexes with a remarkable wide range of metal ions. This relatively small molecule has attracted increasing attention in the field of radiopharmacy, treatment of heavy metal intoxications and nanoparticles preparation. In this review detailed summary of all physical, chemical and biological properties of DMSA and its complex compounds with 99mTc, 186/188Re, 166Ho, 177Lu and 90Y is provided. The clinical utilisation of DMSA complexes in the nuclear medicine and its use for treatment of heavy metal intoxication is briefly summarised. The aspects of its application in the field of nanoparticles preparation is behind the scope of this review, therefore it is only shortly described.

The Hantzsch synthesis with salicylaldehyde revised. On the formation of bridged tetrahydropyridine derivatives

The Hantzsch condensation of salicylaldehyde with ethyl acetoacetate and ammonia has been re-examined. The reaction leads primarily to a 1,4-dihydropyridine intermediate which, after isomerization, undergoes a ring closure to give a bridged 1,4,5,6-tetrahydropyridine product, or is oxidized to 4-methyl-2-(2-oxo-2H-1-benzopyran-3-yl)[1]benzopyrano[3,4-c]pyridin-5-one. Bridged tetrahydropyridines with the 8-oxa-10-azatricyclo[7.3.1.02,7]trideca-2,4,6,11-tetraene skeleton were found in the Hantzsch-type condensation of salicylaldehyde with malononitrile, ammonium acetate, and acetone or butan-2-one. A mechanism for these reactions is discussed.

Cycloaddition of diazomethane to unsymmetrical carbodiimides and mass spectroscopy study of 1,5-disubstituted 1,2,3-Triazoles

By the reaction of unsymmetrically substituted carbodiimides with diazomethane the corresponding 1,2,3-triazoles have been obtained. The structure of the adducts was elucidated by IR, UV,1H-NMR and high resolution mass spectrometry.ZusammenfassungDie Struktur der aus unsymmetrischen Carbodiimiden und Diazomethan gebildeten 1,2,3-Triazolen wurde durch IR-,UV-,1H-NMR- und Massenspektrometrie aufgeklärt.

(5R*,11R*)-5-Methyl-1,2-dihydro-5,11-methano-5H,11H-1,3-thia­zolo[2,3-d][1,3,5]benzoxadiazo­cine

The title compound, C(13)H(14)N(2)OS, crystallizes as a racemate in a non-chiral space group. It represents a conformationally restricted analogue of so-called Biginelli compounds known to exhibit multiple pharmacological activities and was selected for a single-crystal X-ray analysis in order to probe the chemical and spatial requirements of some kinds of activity. It was found that the state of hybridization of the formally aminic nitro-gen of the heterocycle is between sp(2) and sp(3) with the lone-pair electrons partially delocalized through conjugation with the sulfur atom rather than the double bond of the pyrimidine nucleus. As a result, the thia-zolo ring adopts a flat-envelope conformation and the puckering of the central pyrimidine ring is close to a half-chair. The critical phenyl ring is fixed in a pseudo-axial and perpendicular [dihedral angle 84.6 (1)°] orientation with respect to the pyrimidine ring via an oxygen bridge.

Novel heterocycles containing the pyrazole unit

New condensed pyrazolo[1,5-e][1,3,5]benzoxadiazocine and bridged 5,11-methano-[1,2,4]triazolo[1,2-c][1,3,4]benzoxadiazepine heterocyclic ring systems were prepared by cyclizations of 4,5-dihydro-3-methyl-5-(2-hydroxyphenyl)-1H-pyrazole-1-carboximidamide with C1 reagents (triethylorthoformate and 1,1′-carbonyldiimidazole). In contrast, cyclocondensations with C2 and C3 reactants occur exclusively at the amidine moiety yielding substituted pyrano[2,3-d]pyrimidine, pyrimidine, and imidazole derivatives.