Roman Dembinski

Synthesis of diversely 1,3,5-trisubstituted pyrazoles via 5-exo-dig cyclization

5-Exo-dig cyclocondensation of alk-3-yn-1-ones with hydrazines, in the presence of montmorillonite K-10, provides an effective method with a high atom economy for the synthesis of diversely 1,3,5-trisubstituted pyrazoles. The microwave-accelerated reaction proceeds in the absence of solvent and leads to 5-benzyl substituted pyrazoles with good yields (72-91%). The regiochemistry of the process was confirmed by the X-ray crystallographic structure determination of 1-(2-fluorophenyl)-5-(4-methylbenzyl)-3-phenyl-1H-pyrazole.

Alkyne hexacarbonyl dicobalt complexes in medicinal chemistry and drug development

Background: Organometallic alkyne complexes of the hexacarbonyl dicobalt type (hexacarbonyl[µ-h4-(alkyne)]dicobalt (Co – Co) complexes) are an interesting class of compounds used in modern synthetic chemistry and an increasing number of reports deal also with the use of these complexes in the field of medicinal chemistry. Methods: This review highlights the applications of alkyne hexacarbonyl dicobalt species in biomedical research with a focus on anticancer drug development. Medline, Pubmed, Scifinder and Espacenet internet databases were searched for available literature and patents. Results/conclusion: Preclinical studies on hexacarbonyl dicobalt complexes containing various alkyne (bio)ligands demonstrated a high potential for application (e.g., as antitumor drugs, hormonally active or diagnostic agents). The biological properties of the compounds were mainly determined by the nature of the ligands and the presence of the metal center.

Catalyst-free chemo-/regio-/stereo-selective amination of alk-3-ynones. Synthesis of 1,5-benzodiazepines and 3-amino-2-alkenones

Reaction of alk-3-yn-1-ones with o-phenylenediamines provides an effective method with high atom economy for the synthesis of diversely substituted benzodiazepines and conjugated enaminones. This microwave-accelerated reaction proceeds in ethanol in the absence of a catalyst and leads to benzyl-substituted 1,5-benzodiazepines with good yields (70–92%). A room temperature protocol with the same set of reagents (stabilized with triethylamine) leads to enaminones (3-amino-2-alkenones, 70–99%). The tautomer formed and the regio- and stereochemistry of the process are confirmed by the X-ray crystallographic structure determination of 2-(4-methylbenzyl)-4-phenyl-3H-benzo[b][1,5]diazepine and (Z)-3-[(2-amino-4,5-dimethylphenyl)amino]-4-(4-tert-butylphenyl)-1-(4-chlorophenyl)but-2-en-1-one.

CHLORINATION REACTIONS OF PHOSPHORUS THIONOESTERS > P(S)OSiMe3; GENERAL SYNTHESIS OF COMPOUNDS CONTAINING > P(O)SCI FUNCTIONAL GROUP

Abstract Efficient, general synthesis of oxophosphoranesulphenyl chlorides ABP(O)SCl 2 based on the reaction of phosphorus trimethylsilylthionoesters ABP(S)OSiMe3 7 with chlorinating agents is described.

Novel synthesis of symmetrical tetra-alkyl monothiopyrophosphates

Abstract The novel highly efficient synthesis of sym-tetra-alkyl monothiopyrophosphates (RO)2P(O)SP(O) (OR′)2 1 based on the condensation of dialkoxyoxophosphoranesulphenyl chlorides 3 with dialkyltrimethylsilyl phosphites 4 is described.

Reaction of diphosphoryl diselenides with dialkyltrimethylsilyl phosphites: a new route to symmetrical monoselenopyrophosphates

Abstract A novel efficient synthesis of sym-monoselenopyrophosphates 3 based on the reaction of diphosphoryl diselenides 1 with dialkyltrimethylsilyl phosphites 2 is described.

Reaction of oxophosphorane-sulphenyl and -selenenyl chlorides with dialkyl trimethylsilyl phosphites. Novel synthesis of compounds containing a sulphur or selenium bridge between two phosphoryl centres

A novel highly efficient synthesis of sym-tetra-alkyl monothio- and monoseleno-pyrophosphates (RO)2P(O)XP(O)(OR′)2(X = S,Se) based on the condensation of dialkoxyoxophosphorane-sulphenyl or -selenenyl chlorides (RO)2P(O)XCl (X = S,Se) with dialkyl trimethylsilyl phosphites (RO)2POSiMe3(9) is described. Remarkably selective reaction of a O,O′-dialkyl O″-trimethylsilyl selenophosphate (RO)2P(Se)OSiMe3(13) with sulphuryl dichloride in the presence of an equimolar amount of a phosphite (9) leads to the formation of sym-monoselenopyrophosphates in excellent yield. A new rearrangement in phosphorus chemistry, sym-monoselenopyraphosphates (11) to asym-monoselenopyrophosphates (12), has been observed.

Regioselective “hydroamination” of alk-3-ynones with non-symmetrical o-phenylenediamines. Synthesis of diversely substituted 3H-1,5-benzodiazepines via (Z)-3-amino-2-alkenones

The reaction of alk-3-yn-1-ones (a bifunctional reagent) with o-phenylenediamines provides an effective synthetic method with high atom economy for the preparation of diversely substituted 1,5-3H-benzodiazepines. The reaction initially leads to the formation of conjugated enaminones (3-amino-2-alkenones, 51–99%), at room temperature, which constitutes a formal non-catalyzed hydroamination of the non-conjugated alkyne. Non-symmetrical o-phenylenediamines react in a regioselective fashion with respect to amino groups. Both the direct microwave-accelerated reaction of o-phenylenediamines with alkynones in ethanol and the intramolecular cyclization of intermediate enaminones in ethanol/acetic acid lead to substituted 1,5-benzodiazepines with good yields (39–92 and 26–99%). The regio- and stereochemical outcomes of these processes are confirmed by the X-ray structure determination of (Z)-3-[(2-amino-4-methylanilino)-4-(4-methylphenyl)-1-phenylbut-2-en-1-one], 4-[(4-methylphenyl)methyl]-7-nitro-2-phenyl-3H-1,5-benzodiazepine and 6,8-dimethyl-4-(4-methylbenzyl)-2-phenyl-3H-benzo[b][1,5]diazepine.

Synthesis of β-Halofurans

Furans substituted with halogens at the beta carbon, which is less prone to electrophilic reactions compared to an alpha position, are important intermediates for accessing highly substituted furans. The regioselectivity of the introduction of a halogen plays an important role in their preparation. This review summarizes efforts for the synthesis of β-halofurans (but not benzofurans) as sorted by halogen (iodo, bromo, chloro, and fluoro). This article provides general reaction schemes that were confirmed with multiple examples and are sometimes applicable to other halogens, and selected reactions specific to a particular substrate and a halogen.

CRYSTAL AND MOLECULAR STRUCTURE AND SOLID STATE NMR STUDIES OF BIS(5,5-DIMETHYL-2-OXO-1,3,2-DIOXAPHOSPHORINAN-2-YL) SELENIDE

Abstract The structural investigation of the phosphoroorganic selenium-containing title compound C10H20O6P2Se (1) was carried out. The structure of 1 has been determined by X-ray analysis and correlated with the solid state NMR studies, its purity and identity was confirmed by elemental analysis. The following crystal data were found: triclinic, P1, a = 5.6557(6) A, b = 10.2717(8) A, c = 13.761(1) A, α = 105.580(7)β, p = 90.992(7)°, γ = 101.745(8)°, and Z = 2. Two six-membered rings in the molecule of 1 are in the chair conformation. The selenium atom which bridges the rings is situated axially with respect to both rings. The exocyclic oxygens are, consequently, in equatorial positions.