Facile Synthesis of New Spirothiadiazolopyridazines by 1,3‐Dipolar Cycloaddition

New derivatives of the spiro type of pyridazines have been synthesized by 1,3‐dipolar cycloaddition of N‐aryl‐C‐ethoxycarbonylnitrile imines with pyridazin‐3(2H)‐thiones. When the nitrile oxide was used, the corresponding pyridazin‐3(2H)‐one was obtained from the intermediate spirooxathiazole by elimination of isothiocyanate group. The peri‐ and regioselectivity of the reaction were ascertained by X‐ray analysis and ¹³C NMR spectroscopy of the cycloadducts 3–9.     

One-Pot,Fluoride-Promoted Wittig Reaction

A one-pot, fluoride-promoted Wittig reaction was developed. The reactions of ethyl α-bromoacetate with aliphatic, aromatic, and heteroaromatic aldehydes in the presence of tri-n-butylphosphine and tetrabutylammonium fluoride produced α,β-unsaturated esters in good to excellent yields and E-stereoselectivity. Under the same conditions, reactions of ethyl α-bromopropionate, α-bromo acetonitrile, and α-bromoacetophenone with aliphatic and aromatic aldehydes in the presence of tri-n-butylphosphine and tetrabutylammonium fluoride produced the expected α,β-unsaturated derivatives in good E-stereoselectivity. The protocol was extended to semistabilized ylides and applied to the synthesis of some combretastatin analogs.     

Synthesis of Sulfonylurea Derivatives Used as Oral Antidiabetics by the Selenium-Assisted Carbonylation Using Carbon Monoxide with Sulfur

Sulfonylurea derivatives including useful antidiabetics (Tolbutamide, Chlorpropamide) were synthesized in good yields from benzene-sulfonamides with thiocarbamates in the presence of DBU. Thiocarbamates were prepared by the selenium-assisted carbonylation of primary amines with carbon monoxide, sulfur, and methyl iodide under mild conditions.     

Synthesis of Carbonyl Compounds from Alcohols Using Electrochemically Generated Superoxide Ions in RTILs

Abstract

We show that the superoxide ion (O₂ ^??) generated electrochemically from oxygen dissolved in room-temperature ionic liquids (RTILs) reacts with primary and secondary alcohols to form the corresponding ketones and carboxylic acids, respectively. Specifically, we study the conversion of benzhydrol to benzophenone and benzyl alcohol to benzaldehyde/benzoic acid. The kinetics (e.g., rate, selectivity, and yield) for these reactions are also determined as functions of the variations in the structure of the ionic liquids. The RTILs used here are imidazolium-based cations where the functional groups on the imidazolium ring are modified. Specifically, 1-butyl-3-methylimidazolium hexafluorophosphate [bmim][PF₆], 1-butyl-2,3-dimethylimidazolium hexafluorophosphate [bdmim][PF₆], and 1-hexyl-3-methylimidazolium hexafluorophosphate [hmim][PF₆] are used as the reaction medium. These results are compared to an ammonium-based RTIL (N-butyl-N-trimethylammonium bis(trifluoromethylsulfonyl)imide). The results show that the nucleophilic attack by the O₂ ^?? of both the RTIL and the alcohol, especially that of the H atom at the R2 position of the [bmim][PF₆] and [hmim][PF₆], greatly affects the yields. No RTIL degradation products were detected for the reactions in [bdmim][PF₆] and N-butyl-N-trimethylammonium bis(trifluoromethylsulfonyl)imide ionic liquids. For the benzyl alcohol oxidation reaction in the RTIL, N-butyl-N-trimethylammonium bis(trifluoromethylsulfonyl)imide, benzaldehyde formed did not undergo further oxidation to form benzoic acid, which may be due to the greater hydrophobicity of this RTIL. The competitive reaction kinetics between the alcohol and RTIL component must be considered in the selection of the RTIL solvent system.     

Synthesis Of 2-Acyltetrahydro-β-Carbolines By An Intramolecular α-Amidoalkylation Reaction

2-Acyltetrahydro-β-carbolines 7 have been obtained by cyclization of adducts 5 from imines 3 of tryptamine 1 and aldehydes 2 with acyl chlorides 4 as a result of an intramolecular a-amidoalkylation reaction in the presence of bases as N,N-dimethylaniline or Et₃N.     

Palladium-Catalyzed Arylation and Vinylation of 2,3-Dihydrofuran with Hypervalent Iodonium Salts

The palladium-catalyzed arylation and vinylation of 2,3-dihydrofuran with aryl and alkenyl iodonium salts afforded 2-phenyl- or 2-alkenyl-2,5-dihydrofurans at room temperature in an aqueous medium.     

Efficient and Green Syntheses of 12-Aryl-2,3,4,12-tetrahydrobenzo[b]xanthene-1,6,11-triones in Water and Task-Specific Ionic Liquid

Facile and convenient one-pot cascade/tandem approaches for the syntheses of privileged medicinal scaffolds, 12-aryl-2,3,4,12-tetrahydrobenzo[b]xanthene-1,6,11-trione derivatives, have been reported under extremely mild reaction conditions using a catalytic amount of H₂SO₄ in water or in the presence of the acidic ionic liquid bmim[HSO₄], which could be recycled.

Supplemental materials are available for this article. Go to the publisher's online edition of Synthetic Communications® to view the free supplemental file.     

Primary Studies on Variation in Position of Trifluoromethyl Groups in Several Aromatic Group‐14 Derivatives by 19F‐NMR Spectroscopy

Variation in the position of CF₃ groups in several aromatic Group‐14 compounds was studied by ¹⁹F‐NMR spectroscopy. In these compounds R_nECl_4?n (n=1 or 2; E=Si, Ge, or Sn; R=2,4,6‐(CF₃)₃C₆H₂ (=Ar), 2,6‐(CF₃)₂C₆H₃ (=Ar′), or 2,4‐(CF₃)₂C₆H₃ (=Ar″)), Ar, Ar′, and Ar″ are all bulky, strongly electron‐withdrawing ligands. The ¹⁹F‐NMR studies of the variation in position of the CF₃ substituents in these compounds as revealed by chemical shifts could be correlated with the electronegativities of the central elements E, and with intramolecular E–F interactions derived from single‐crystal X‐ray diffraction data. These interactions are considered to play an important role in the stabilization of these compounds.     

Studies towards the Synthesis of Alkyl N‐(4‐Nitrophenyl)‐3/2‐oxomorpholine‐2/3‐carboxylates

The syntheses of methyl 4‐(4‐nitrophenyl)‐3‐oxomorpholine‐2‐carboxylate ( 3a ) and ethyl 4‐(4‐nitrophenyl)‐2‐oxomorpholine‐3‐carboxylate ( 5b ), important building blocks for the synthesis of factor Xa inhibitor rivaroxaban analogs with potential dual antithrombotic activity, via Rh₂(OAc)₄‐catalyzed O? H and N? H carbene insertion reactions are described.     

Pinacol Rearrangement of 3,4‐Dihydro‐3,4‐dihydroxyquinolin‐2(1H)‐ones: An Alternative Pathway to Viridicatin Alkaloids and Their Analogs

3‐Alkyl/aryl‐3‐hydroxyquinoline‐2,4‐diones were reduced with NaBH₄ to give cis‐3‐alkyl/aryl‐3,4‐dihydro‐3,4‐dihydroxyquinolin‐2(1H)‐ones. These compounds were subjected to pinacol rearrangement by treatment with concentrated H₂SO₄, resulting in 4‐alkyl/aryl‐3‐hydroxyquinolin‐2(1H)‐ones. When a benzyl (Bn) group was present in position 3 of the starting compound, its elimination occurred during the rearrangement, and the corresponding 3‐hydroxyquinolin‐2(1H)‐one was formed. The reaction mechanisms are discussed for all transformations. All compounds were characterized by IR, ¹H‐ and ¹³C‐NMR spectroscopy, as well as mass spectrometry.