Synthesis of chromeno[3,4-c][1,2]oxazine-N-oxides via formal [4+2] cycloaddition of 3-nitro-2-trihalomethyl-2H-chromenes with cyclohexanone and pinacolone enamines

3-Nitro-2-trichloro(trifluoro)methyl-2H-chromenes undergo a formal [4+2] cycloaddition reaction to cyclohexanone and pinacolone enamines, producing chromeno[3,4-c][1,2]benzoxazin-6-oxides with high diastereoselectivity and in good yields. In addition, some novel 2,3,4-trisubstituted chromanes were obtained. The stereochemistry of the products was established based on a 2D NOESY experiment and an X-ray diffraction study.     

Vinylogous N,N-dimethylaminomethylenation of 3-[(1-substituted)ethylidene]-oxindoles with N,N-dimethylformamide dimethylacetal

An efficient stereoselective synthesis of various 3-(3-dimethylaminoprop-2-enylidene)oxindoles has been disclosed. The compounds were synthesized via a vinylogous N,N-dimethylaminomethylenation at the γ-position of 3-[(1-substituted)ethylidene]oxindoles with DMF-DMA.     

Simple synthesis of functionalized 7-aza-2H-chromenes from pyridoxal and nitroalkenes in aqueous medium

A reaction of 1-nitro-3,3,3-trichloro(trifluoro)propenes and β-nitrostyrene with pyridoxal hydrochloride in the presence of sodium hydroxide in aqueous medium gives good yields of new derivatives of 7-aza-2H-chromene system.     

A novel convenient synthesis of 5-acyl-1,2-dihydropyrimidin-2-ones via 4-trichloromethyl-1,2,3,4-tetrahydropyrimidin-2-ones

A novel four-step methodology for the synthesis of 5-acyl-1,2-dihydropyrimidin-2-ones has been developed. The reaction of readily available N-[(1-acetoxy-2,2,2-trichloro)ethyl]ureas with Na-enolates of 1,3-diketones or β-oxoesters followed by heterocyclization-dehydration of the oxoalkylureas formed gave 5-acyl-4-trichloromethyl-1,2,3,4-tetrahydropyrimidin-2-ones. The latter, in the presence of NaH, eliminate CHCl₃ to give the target compounds.     

Reactions of 3,3,3-trichloro(trifluoro)-1-nitropropenes with 2-morpholinoalk-1-enes

The reaction of 3,3,3-trichloro(trifluoro)-1-nitropropenes with 2-morpholinoalk-1-enes affords the nitroalkylated Z-enamines whose subsequent hydrolysis results in 2-trihalomethyl-1-nitroalkan-4-ones.     

Efficient stepwise and one pot three-component synthesis of 2-amino-4-(2-oxo-2H-chromen-3-yl)thiophene-3-carbonitriles

Environmentally benign conditions have been developed for the synthesis of 2-amino-4-(2-oxo-2H-chromen-3-yl)thiophene-3-carbonitriles (3) starting from 3-acetyl-2H-chromen-2-one (1) through the intermediacy of 2-(1-(2-oxo-2H-chromen-3-yl)ethylidene)malononitrile (2) using the Knoevenagel condensation followed by the Gewald reaction. Alternatively, 3 could also be prepared in a one pot method by treating equimolar amounts of 1, malononitrile, and elemental sulfur. The merits of this preparation are mild reaction conditions, easy work-up procedure, and good yields.     

Reactions of (E)-3,3,3-trichloro(trifluoro)-1-nitropropenes with enamines derived from cycloalkanones. A new type of ring-chain tautomerism in a series of cyclobutane derivatives and stereochemistry of the products

Depending on the reaction conditions, the reactions of (E)-3,3,3-trichloro-1-nitropropene with cyclohexanone enamines led to bicyclo[4.2.0]octanes or trisubstituted enamines, which are the ring-chain tautomers capable of reversible transformations. Diastereoselectivity of the reactions of (E)-3,3,3-trichloro(trifluoro)-1-nitropropenes with cycloalkanone enamines were studied, a series of hitherto unknown CX₃-containing nitroalkylated enamines and γ-nitro ketones were synthesized, the structures of novel compounds were determined by NMR spectroscopy and X-ray diffraction.     

2-Cyanopyridazin-3(2H)-ones: effective and chemoselective electrophilic cyanating agents

2-Cyanopyridazin-3(2H)-ones are novel, effective, selective and electrophilic cyanating agents. A variety of amino, thiol and carbon nucleophiles are chemoselectively N-, S- or C-cyanated in excellent yield using 2-cyanopyridanzin-3(2H)-ones in water or tetrahydrofuran.     

A one-pot synthesis and mild cleavage of 2-[2- or 5-(alkylsulfanyl)pyrrol-1-yl]ethyl vinyl ethers by t-BuOK/DMSO: a novel and facile approach to N-vinylpyrroles

Substituted N-[2-(vinyloxy)ethyl]pyrroles, prepared in good yield through an allenic or acetylenic carbanion/isothiocyanate one-pot methodology from 2-(vinyloxy)ethyl isothiocyanate and allyloxyallene, methoxyallene, N,N-dimethyl-2-propyn-1-amine, and 3-methoxy-1-(methylsulfanyl)-1-propyne, are smoothly converted into the corresponding N-vinylpyrroles using t-BuOK/DMSO (room temperature). The reaction proceeds via elimination of vinyl alcohol from the N-[2-(vinyloxy)ethyl] substituent and represents a novel approach to N-vinylpyrroles.     

Two-pot synthesis of N,N-disubstituted 4H-3,1-benzothiazin-2-amines from aryl(2-isothiocyanatophenyl)methanones and secondary amines

A convenient synthesis of N,N-disubstituted 4H-3,1-benzothiazin-2-amines from aryl(2-isothiocyanatophenyl)methanones using a two-pot procedure has been developed. Thus, treatment of these isothiocyanato ketones with secondary amines gave the corresponding keto thioureas, which were allowed to react with sodium borohydride or methylmagnesium bromide to afford 1,1-dialkyl-3-{2-[aryl(hydroxy)methyl]phenyl}thioureas or 1,1-dialkyl-3-[2-(1-aryl-1-hydroxyethyl)phenyl]thioureas, respectively, in one pot. Hydrobromic acid-mediated cyclization of these hydroxy thiourea precursors provided the desired 4H-3,1-benzothiazin-2-amines.     

New approach to 5-arylsulfonyl-substituted 1,2-dihydropyrimidin-2-ones via base-induced chloroform elimination from 4-trichloromethyl-1,2,3,4-tetrahydropyrimidin-2-ones

A four-step method for the synthesis of 5-arylsulfonyl-substituted 1,2-dihydropyrimidin-2-ones has been developed. The reaction of readily available N-[(1-acetoxy-2,2,2-trichloro)ethyl]ureas with sodium enolates of α-arylsulfonylketones followed by heterocyclization-dehydration of the oxoalkylureas formed gave 5-arylsulfonyl-4-trichloromethyl-1,2,3,4-tetrahydropyrimidin-2-ones. The latter, in the presence of strong bases, eliminate CHCl₃ to give the target compounds.     

The interaction of fluorinated 2-arylhydrazono-1,3-dicarbonyl compounds with o-phenylenediamine

2-Arylhydrazono-3-fluoroaklyl-3-oxo esters react with o-phenylenediamine under neutral conditions to form mainly o-aminoanilides, from which can be obtained 1,5-benzodiazepin-2-ones. Ethyl-2-(benzimidazol-2-yl)-2-(4-methylphenyl)hydrazonoethanoate was isolated also from the reaction of di(tri)fluoromethyl-containing 2-arylhydrazono-3-oxo esters. The reactions of o-phenylenediamine with 1,2,3-triketone 2-arylhydrazones containing alkyl substituents result in the formation of 1-(benzimidazol-2-yl)-1,2-dioxoalkane arylhydrazones, whereas phenylsubstituted analogues afford 2-phenylbenzimidazole. Nickel(II) chelates of N,N′-phenylene-bis(2-arylazo-1,3-aminovinylketones) were obtained from 1,2,3-triketone 2-arylhydrazones and o-phenylenediamine using a template method.     

Syntheses and structures of iron carbonyl complexes derived from N-(5-methyl-2-thienylmethylidene)-2-thiolethylamine and N-(6-methyl-2-pyridylmethylidene)-2-thiolethylamine

The reaction of N-(5-methyl-2-thienylmethylidene)-2-thiolethylamine (1) with Fe₂(CO)₉ in refluxing acetonitrile yielded di-(μ₃-thia)nonacarbonyltriiron (2), μ-[N-(5-methyl-2-thienylmethyl)-η¹:η¹(N);η¹:η¹(S)-2-thiolatoethylamido]hexacarbonyldiiron (3), and N-(5-methyl-2-thienylmethylidene)amine (4). If the reaction was carried out at 45 °C, di-μ-[N-(5-methyl-2-thienylmethylidene)-η¹(N);η¹(S)-2-thiolethylamino]-μ-carbonyl-tetracarbonyldiiron (5) and trace amount of 4 were obtained. Stirring 5 in refluxing acetonitrile led to the thermal decomposition of 5, and ligand 1 was recovered quantitatively. However, in the presence of excess amount of Fe₂(CO)₉ in refluxing acetonitrile, complex 5 was converted into 2-4. On the other hand, the reaction of N-(6-methyl-2-pyridylmethylidene)-2-thiolethylamine (6) with Fe₂(CO)₉ in refluxing acetonitrile produced 2, μ-[N-(6-methyl-2-pyridylmethyl)-η¹ (N_py);η¹:η¹(N); η¹:η¹(S)-2-thiolatoethylamido]pentacarbonyldiiron (7), and μ-[N-(6-methyl-2-pyridylmethylidene)-η²(C,N);η¹:η¹(S)-2- thiolethylamino]hexacarbonyldiiron (8). Reactions of both complex 7 and 8 with NOBF₄ gave μ-[(6-methyl-2-pyridylmethyl)-η¹(N_py);η¹:η¹(N);η¹:η¹(S)-2-thiolatoethylamido](acetonitrile)tricarbonylnitrosyldiiron (9). These reaction products were well characterized spectrally. The molecular structures of complexes 3, 7-9 have been determined by means of X-ray diffraction. Intramolecular 1,5-hydrogen shift from the thiol to the methine carbon was observed in complexes 3, 7, and 9.     

Syntheses, characterization, X-ray crystal structures and emission properties of five oxovanadium(V) complexes with pyridyl/pyrimidyl-pyrazole derived ditopic ligands

Four oxovanadium(V) complexes of heterocycle based ditopic ligands PyPzOAP (N-[amino(pyridin-2-yl)methylidene]-5-methyl-1-(pyridin-2-yl)-1H-pyrazole-3-carbohydrazonic acid), PyPzOAPz (N-[amino(pyrazin-2-yl)methylidene]-5-methyl-1-(pyridin-2-yl)-1H-pyrazole-3-carbohydrazonic acid), PymPzOAP (N-[amino(pyridin-2-yl)methylidene]-1-(4,6-dimethylpyrimidin-2-yl)-5-methyl-1H-pyrazole-3-carbohydrazonic acid) and PyPzCAP (5-methyl-1-(pyridin-2-yl)-N′-[1-(pyridin-2-yl)ethylidene]-1H-pyrazole-3-carbohydrazide) and a binuclear (di-μ-oxo) oxovanadium(V) complex of the ligand PymPzCAP (1-(4,6-dimethylpyrimidin-2-yl)-5-methyl-N′-[1-(pyridin-2-yl)ethylidene]-1H-pyrazole-3-carbohydrazide) have been investigated. The ligands act as uninegative NNO tridentates donors for the VO₂⁺ ion exhibiting their monotopicity. The ligands show varying emission properties due to the presence of fluophoric groups like 1-(2-pyridyl)pyrazole or 1-(2-pyrimidyl)pyrazole. The vanadium(V) complexes show fluorescence quenching with respect to the used ligands to a varying extent. The complexes were characterized by UV-Vis, IR, cyclic voltammetry and X-ray crystallography.     

N-Polyfluoroethyl and N-2-chlorodifluorovinyl derivatives of azoles

Reactions of tetrafluoroethylene, chlorotrifluoroethylene and 1,2-dichlorodifluoroethylene with N-potassium salts of imidazole, 2-methylbenzimidazole, 3,5-dimethylpyrazole, 1,2,4-triazole, and benzotriazole lead to the formation of the corresponding N-(1,1,2,2-tetrafluoroethyl), N-(2-chloro-1,1,2-trifluoroethyl), and N-(2-chloro-1,2-difluorovinyl) azoles. Treatment of N-(2-chloro-1,2-difluorovinyl) and N-(2-chloro-1,1,2-trifluoroethyl) derivatives of azoles with tetramethylammonium fluoride is a useful synthetic method for the preparation of heterocycles with 1,2,2,2-tetrafluoroethyl group attached to nitrogen.     

Pd2dba3/P(i-BuNCH2CH2)3N: a highly efficient catalyst for the one-pot synthesis of trans-4-N,N-diarylaminostilbenes and N,N-diarylaminostyrenes

A Pd₂dba₃/P(i-BuNCH₂CH₂)₃N catalyzed one-pot synthesis of unsymmetrically substituted trans-4-N,N-diarylaminostilbenes and both symmetrically and unsymmetrically substituted N,N-diarylaminostyrene derivatives is reported. The procedure involves two or more palladium catalyzed sequential coupling reactions (an amination and an inter-molecular Heck reaction) in one-pot using the same catalyst system with two different aryl halides, including aryl chlorides and hetero aryl halides as the coupling partners.     

Design and synthesis of boron containing 2,4-disubstituted-phthalazin-1(2H)-one and 3,7-disubstituted-2H-benzo[b][1,4] oxazine derivatives as potential HGF-mimetic agents

We synthesized boron containing 2-(4-methoxybenzyl)-4-(4-(4,4,5,5-tetramethyl-1,3,2-dioaborolan-2-yl)phenyl) phthalazin-1(2H)-one 3 and 7-methyl-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-2H-benzo[b][1,4] oxazine 8. The reaction of compound 2 with B₂pin₂ using potassium acetate as the base and Pd(PPh₃)₂Cl₂ as the catalyst, produced the corresponding boron-containing derivative 3 as a white solid in 65% yield. Alternatively, we have synthesized compound 8 as a yellow solid in 59% yield using the Miyaura borylation reaction. The potassium trifluoro(4-(-methyl-2H-benzo[b][1,4]oxazine-3-yl)phenylborate 9 was then obtained after treatment of 8 with aqueous solution of KF₂H in methanol as white solid product in 60% yield. The biological activities of the synthetic compounds are currently being evaluated.     

Synthesis of 1H-pyrrolo[3,2-c]quinoline derivatives via palladium-catalyzed heteroannulation of 2-aryl-3-iodo-4-(phenylamino)quinolines and 4-(N,N-allylphenylamino)-2-aryl-3-iodoquinolines

Palladium(0)/copper iodide catalyzed Sonogashira cross-coupling of 2-aryl-3-iodo-4-(phenylamino)quinolines with terminal alkynes afforded series of 1,2,4-trisubstituted 1H-pyrrolo[3,2-c]quinolines in a single-step operation. Conversely, the 4-(N,N-allylphenylamino)-2-aryl-3-iodoquinoline derivatives were found to undergo PdCl₂(PPh₃)₂/CuI catalyzed intramolecular Heck reaction to yield the corresponding 1,3,4-trisubstituted 1H-pyrrolo[3,2-c]quinolines.     

Base promoted facile route to functionalized benzo[b][1,8]naphthyridin-2-(1H)-ones from N-benzyl-N-(3-cyanoquinolin-2-yl)acetamides

A facile synthesis of 4-amino-N-benzylbenzo[b][1,8]naphthyridin-2(1H)-ones 3 is described from N-benzyl-N-(3-cyanoquinolin-2-yl)acetamides 2 with t-BuOK in excellent yields in mild conditions. These reactions proceeded at room temperature under aerobic atmosphere in very short period. The cyclization reactions were also extended with N-alkyl amino acetamide analogues affording the products in good yields.     

PTSA catalyzed straightforward protocol for the synthesis of 2-(N-acyl)aminobenzimidazoles and 2-(N-acyl)aminobenzothiazoles in PEG

An efficient PTSA catalyzed synthesis of 2-(N-acyl)aminobenzimidazoles and 2-(N-acyl)aminobenzothiazoles has been described using S-ethylated-N-acylthioureas as substrates and polyethylene glycol as solvent.