Concise synthesis of ω-fluoroalkylated ketoesters. A building block for the synthesis of six-, seven-, and eight-membered fluoroalkyl substituted 1,2-diaza-3-one heterocycles

A concise and general synthetic route toward the small and medium-sized fluoroalkyl substituted 1,2-diaza-3-one heterocyclic ring skeletons via a sequential reaction of condensation and ring-closure reaction of ω-fluoroalkylated ketoesters 4 with hydrazines 5 catalyzed by 10-20 mol % TsOH has been developed. A practical preparation of biologically interested ω-fluoroalkylated ketoesters 4, which were subsequently subjected as a fluorine-containing building block to the synthesis of 1,2-diaza-3-one heterocycles has been optimized. Trifluoromethyl substituted seven- and eight-membered 1,2-diazapinone 8, 1,2-diazocinone 10 were also obtained via this sequential reaction of δ- (or ?-) trifluoromethyl ketoesters with hydrazine hydrates in acidic condition. In contrast, the sequential reaction of ω-fluoroalkylated δ- or ?-ketoesters with aryl hydrazines under the same conditions did not result in the formation of diazepinones and diazocinones, and instead, the reaction provided a direct access to the biologically important 2-fluoroalkyl-indole-3-carboxylate derivatives via a Fisher indole synthesis.     

A stereo,regioselective synthesis and discovery of antimycobaterium tuberculosis activity of novel β-lactam grafted spirooxindolopyrrolidine hybrid heterocycles

A stereo- and regioselective synthesis of hitherto unexplored novel class of β-lactam embedded spirooxindolopyrrolidine hybrid heterocycles have been accomplished via ionic liquid accelerated [3 + 2]-cycloaddition reaction process. The expected unusual lactonization/lactamization product could not be observed even in traces. The in vitro antimycobacterium tubercular activity of the synthesized spiroheterocyclic hybrids were assessed against Mycobacterium tuberculosis H37Rv. Among them, the compounds with no substitution and chlorosubstitution on the oxindole ring showed the most potent activity with a MIC 0.78 μg/mL and 1.56 μg/mL, respectively which were two-fold and equal activity than the standard drug, ethambutol (MIC = 1.56 μg/mL).     

A novel and efficient total synthesis of(±)-Cembrene-A

(±)-Cembrene-A,a highly active scent-trail pheromone,was first isolated from thetermite(Nasutitermes exitiosus)and its structure was established by using chemical and spectralmethods,Afterwards,it was also found in some plants and soft corals.In view of itsbiological activity,some total syntheses have been reported.It was reported that its dl-form showed the same order of activity as that of the natural pheromone,In previous work,     

β-(Cycloalkylamino)ethanesulfonyl azides as novel water-soluble reagents for the synthesis of diazo compounds and heterocycles

Chemistry of Heterocyclic Compounds - Novel water-soluble sulfonyl azides were synthesized, which are basic by nature. The obtained compounds were used as donors of the diazo group in the diazo...     

A novel and stereoselective synthesis of (±)-cephalotaxine and its analogue

Cephalotaxine (1) and its analogue (3) were stereoselectively synthesized from proline via the pyrrolobenzazepine (4) through Claisen rearrangement, cationic cyclization, and regio- and stereo-selective hydroxylation.     

A one-pot reaction of (chlorocarbonyl) phenyl ketene with β-ketoamides and thiochromen-2-one

Readily available (chlorocarbonyl)phenyl ketene and a varied set of β-ketoamides were reacted in a one-step procedure to produce 2-pyrone derivatives. β-Ketoamide derivatives are versatile intermediates for the synthesis of heterocyclic compounds. For instance, 1-morpholino-3-phenyl-1,3-propanedione, 1-phenyl-3-piperidino-1,3-propanedione, 1-phenyl-3-pyrrolidino-1,3-propanedione, 1-piperidino-1,3-butanedione, 1-morpholino-2-phenyl ethanone were used in these reactions to produce 2-pyrone derivatives. In addition, the preparation of 4-hydroxy-3-phenylthiochromeno[4,3-b]pyran-2,5-dione derivatives and 4-hydroxy-7-methyl-3-phenyl pyrano[3,2-c]chromeno-2,5-dione were described. For the synthesis of these compounds 4-hydroxy-2H-thiochromen-2-ones and 4-hydroxy-8-methyl-2H-chromen-2-one were reacted with (chlorocarbonyl)phenyl ketene and the final products were isolated in good yields.     

β-Nitroacrylates and silyl enol ethers as key starting materials for the synthesis of polyfunctionalized β-nitro esters and 1,2-oxazine-2-oxides

The reaction of silyl enol ethers with β-nitroacrylates, in the presence of tetrabutyl ammonium fluoride as catalyst, allows the formation of polyfunctionalized β-nitro esters, or hexahydro-4H-benzoxazine-2-oxides, depending on the nature of the starting silyl enol ethers.     

Synthesis of 3-(arylamino)-5-bromo-2-phenyl-2,3-dihydro-2λ5-benzo[d][1,2]-oxaphosphol-2-oxides

An efficient synthesis of cis-3-(arylamino)-5-bromo-2-phenyl-2,3-dihydro-2λ⁵-benzo[d][1,2]-oxaphosphol-2-oxides 4a–h is described involving a three-component reaction of dichlorophenylphosphine (2), 5-bromosalicylaldehyde (1), and different substituted aromatic primary amines (3) in anhydrous benzene. The product structures were characterized by IR and NMR spectral data.     

A Convenient Synthesis of cis and trans-(±)-4-Amino-1-[2-(hydroxyl-methyl)-1,3-oxathiolan-5-yl]-2(1H)-pyrimidinone

A convenient synthesis of cis-(±) isomer 1 and trans-(±) isomer 2 of lamivudine starting from benzoyloxyacetaldehyde and l,4-dithiane-2,5-diol is described. The key steps include chlorination of oxathiolane lactol 5 by SOCl2/DMF, followed by coupling with silylated N4-acetylcytosine and deprotection. The overall yield was 42.6 % and 20.1 %, respectively.     

A Facile and Efficient Synthesis of (±)-Tropan-2-one

The facile and efficient multigram synthesis of (±)-tropan-2-one 1 was achieved in six steps (65% overall yield) from N-methyl-3-oxopyridyl hydroiodide 3.     

Indole derivatives. 138. Synthesis of α-(5-indolyl)ethylamine and 5-(2-aminoethoxy)- and 5-(aminoethylthio)tryptamines

The reaction of 5-acetylindole with hydroxylamine with subsequent reduction of the resulting oxime gave -(5-indolyl)ethylamine. Coupling of 4-(2-phthalimidoethoxy)- and 4-(2-phthalimidoethylthio)phenyldiazonium chlorides with ethyl -acetyl--phthalimidovalerate, subsequent cyclization of the resulting hydrazones, hydrolysis, decarboxylation, and removal of the phthalyl protecting group led to the formation of 5-(2-aminoethoxy)- and 5-(2-aminoethylthio)tryptamines, respectively.For Communication 137, see [1].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 46–48, January, 1992.     

α-aminoazoles in synthesis of heterocycles: IV. Regiodirection of 3(5)-amino-5(3)-methylpyrazole reaction with hexafluoroacetylacetone

The reaction of 3(5)-amino-5(3)-methylpyrazole with hexafluoroacetylacetone depending on the process conditions led to the formation either of pyrazolo[1,5-a]pyrimidine or pyrazolo[3,4-b]-pyridine. By means of 2D NMR spectroscopy the structure was established of a stable intermediate product, 2-methyl-5,7-bis(trifluoromethyl)-4,5,6,7-tetrahydropyrazolo[1,5-a]-pyrimidine-5,7-diol, whose dehydration yielded the above compounds.     

2-Polyfluoroalkylchromones. 11. Synthesis and structures of 5-hydroxy-3-(2-hydroxyaryl)-5-polyfluoroalkyl-Δ2-pyrazolines and 3(5)-(2-hydroxyaryl)-5(3)-polyfluoroalkylpyrazoles

The reaction of 2-hydroxy-2-polyfluoroalkylchroman-4-ones with hydrazine affords 5-hydroxy-3-(2-hydroxyaryl)-5-polyfluoroalkyl-²-pyrazolines, whereas 2-polyfluoroalkylchromones under similar conditions produce 3(5)-(2-hydroxyaryl)-5(3)-polyfluoroalkylpyrazoles. 5-(2-Hydroxyaryl)-1-methyl-3-polyfluoroalkylpyrazoles were synthesized in the reaction with methylhydrazine, and the reaction with phenylhydrazine afforded regioisomeric 3(5)-(2-hydroxyphenyl)-1-phenyl-5(3)-polyfluoroalkylpyrazoles.     

A novel and efficient synthesis of (+)- and (−)-trans-2-aminocyclohexanol by enzymatic hydrolysis

Both enantiomers of trans-2-aminocyclohexanol were obtained by enzymatic hydrolysis of (±)-2-azidocyclohexanoates using lipases and subsequent hydrogenation.     

A new approach to (±)-heritonin. The preparation of β-tetralones from allylsilanes and acid chlorides

A new method for the preparation of 4-alkyl-β-tetralones is described, by reaction of arylacetic acid chlorides with allylsilanes. Employing β-tetralone 5, the synthesis of (±)-heritonine and (±)-epi-heritonine, natural piscicides isolated from Heritiera littoralis, was achieved in four steps and 22% overall yield. The key step of this synthesis involved the selenocarbenium ion-mediated elaboration of the butenolide ring of the natural product.     

Synthesis and Crystal Structure of 2-(4-Nitrophenyl)-1,2-benzisoselenazol-3(2H)-one DMF (1:1) Solvate

The title compound (C13H8N2O3Se-C3H7NO) has been synthesized by a simple synthetic route and by recrystallization from DMF. The molecular structure of this compound was obtained by single-crystal X-ray diffraction. The compound crystallized in the triclinic space group P with a = 7.450(6), b = 8.150(7), c = 13.859(12) , α = 75.014(14), β = 83.072(18), γ = 84.409(14)°, V = 805.0(12)3, Z = 2 and R = 0.0271 for 2575 observed reflections with I > 2σ(I). X-ray analysis reveals that not only intermolecular Se…O and C-H…O interactions, but also π…π stacking interactions exist in the adjacent molecules. The above three kinds of intermolecular interactions extend the complex into an infinite three-dimensional layered network.     

Enantioselective synthesis of β-amino acids. Part 10: Preparation of novel α,α- and β,β-disubstituted β-amino acids from (S)-asparagine

Perhydropyrimidinone (S)-1 is alkylated with very high diastereoselectivity to give trans products (2S,5R)-3, (2S,5R)–4 and (2S,5R)-5. Dialkylation of (S)-1 also proceeds with complete stereoselectivity to afford adducts (2S,5R)-6, (2S,5S)-6, (2S,5R)-7 and (2S,5S)-7. Hydrolysis (6N HCl, 100°C) of monoalkylated derivative (2S,5R)-3 gives enantiopure α-substituted β-amino acid (R)-8. Hydrolysis of dialkylated adducts 6 and 7 affords enantiopure α,α-disubstituted β-amino acids (R)- or (S)-9 and (R)- or (S)-10. Related iminoester (2S,6S)-2 is alkylated with complete diastereoselectivity to give products (2S,6S)-11–13 whose hydrolysis under relatively mild conditions (2N CF₃CO₂H, CH₃OH, 100°C) affords enantiopure N-benzoylated β,β-disubstituted β-amino acid esters (S)-14–16, with intact double bonds in the olefinic substituents.