Divergent synthesis of spirocyclopentene-pyrazolones and pyrano[2,3-c]-pyrazoles via Lewis base controlled annulation reactions

An effective Lewis base catalyst-controlled α-regioselective annulation reaction of γ-substituted allenoates with unsaturated pyrazolones has been developed, affording various spirocyclopentene-pyrazolones and pyrano[2,3-c]pyrazoles. The combination of PPh₃ and K₂CO₃ promoted the [3+2] annulation to access the spirocyclopentene-pyrazolones in moderate to good yields (up to 90%) with excellent diastereoselectivities (dr >19:1), while [4+2] annulations to generate pyrano[2,3-c]pyrazoles were successfully achieved by employing DBU as catalyst (in up to 92% yield). Of importance, the asymmetric synthesis of spirocyclopentene-pyrazolone was realized by using our previously reported chiral ferrocenylphosphine catalyst.     

Heterodiene syntheses—XII : The conformational analysis of cis and trans 2-alkoxy-4-phenyl-2,3-dihydropyran[2,3-c] pyrazoles: Steric interactions and the anomeric effect

The conformational equilibria of a homogeneous series of cis and trans 2-alkoxy-4-phenyl-2,3-dihydropyran[2,3-c] pyrazoles have been investigated by a graphical method, and the preferences are rationalized in terms of steric interactions between the 4 and 5-substituents and of the anomeric effect.The anomeric interaction depends upon the nature of the alkoxy group and the conformational free-energy differences correlate with the steric parameters E_s.     

An efficient and highly stereoselective synthesis of novel trifluoromethylated trans-dihydrofuro[2,3-c]pyrazoles using arsonium ylides

An efficient approach of highly stereoselective synthesis of novel trifluoromethylated trans-4,5-dihydrofuro[2,3-c]pyrazoles has been described. Arsonium bromides 1 reacted smoothly with the electron-deficient alkenes (Z)-4-aryl-1-phenyl-3-(trifluoromethyl)-1H-pyrozol-5(4H)-ones 2 to give products trans-dihydrofuro[2,3-c]pyrazoles 3 with high stereoselectivity and in good to excellent yields, using CH₂Cl₂ as solvent and K₂CO₃ as base.     

A green and practical method for the synthesis of novel pyrano[2,3-<Emphasis Type="Italic">c</Emphasis>]pyrazoles and <Emphasis Type="Italic">bis</Emphasis>-pyrano[2,3-<Emphasis Type="Italic">c</Emphasis>]pyrazoles using sulfonic acid-functionalized ionic liquid

An efficient and practical protocol was developed for the synthesis of novel pyrano[2,3-c]pyrazoles and bis-pyrano[2,3-c]pyrazoles by one-pot four-component reaction of arylaldehyde, ethyl acetoacetate, hydrazine hydrate and dimethyl malonate using SO₃H-functionalized ionic liquid [DMBSI]HSO₄ as a potential green catalyst under solvent-free condition. The method presented is mild, environmentally friendly, inexpensive and functionality tolerant and produces the desired pyranopyrazoles in short reaction times (17–24 min) and excellent yields (85–95%). In addition, the catalyst can be reused at least ten times without almost any change in its catalytic activity.     

Novel Approaches to Synthesis of 4-Alkyl-6-amino-5-cyano-3-methyl(propyl, phenyl)-2H,4H-pyrano[2,3-c]pyrazoles

We have obtained 4-alkyl-6-amino-5-cyano-3-methyl(propyl, phenyl)-2H,4H-pyrano[2,3-c]pyrazoles by reaction of 4-alkylmethylene-3-substituted 5-pyrazolones with malononitrile or cyanothioacetamide. We have used X-ray diffraction to study the structure of 6-amino-5-cyano-4-isopropyl(hexyl)-3-phenyl-2H,4H-pyrano[2,3-c]pyrazoles.     

RuCl3/SnCl2 mediated synthesis of pyrrolo[2,3-c]carbazoles and consequent preparation of indolo[2,3-c]carbazoles

A simple method for the synthesis of pyrrolo[2,3-c]carbazoles from N-alkylated-3-aminocarbazole derivatives and ethylene glycol has been developed via heteroannulation reaction using RuCl₃/SnCl₂ system. Moreover indolo[2,3-c]carbazoles were prepared from various pyrrolo[2,3-c]carbazoles in good yields.     

Synthesis of heterocyclic compounds from 4-formylpyrazoles

Formylation of pyrazole and 2,5-dimethylpyrazole gave a number of pyrazole-containing aldehydes, which can be used to obtain chromenes, tetrahydrochromenes, 1,4-dihydropyrano[2,3-c]pyrazoles, pyrano[3,2-c]chromenes, thiochromeno[4,3-b]pyrans, pyrano[3,2-c]-quinolines, and thiazolo[3,2-a]pyridines.     

Substituted chromones in [3+2] cycloadditions with nonstabilized azomethine ylides: synthesis of 1-benzopyrano[2,3-c]pyrrolidines and 1-benzopyrano[2,3-c:3,4-c′]dipyrrolidines

Chromones bearing electron-withdrawing substituents at the 2- or 3-position react with nonstabilized azomethine ylides to produce 1-benzopyrano[2,3-c]pyrrolidines in good yields. Reactions of 3-cyanochromones proceed diastereoselectively to give 1-benzopyrano[2,3-c]pyrrolidines and tetrahydro-1H-spiro[chromeno[2,3-c]pyrrol-9,5′-oxazolidine]-9a-carbonitriles, depending on the reactant ratio, as a result of a 1,3-dipolar cycloaddition of the azomethine ylide at the double bond and carbonyl group of the chromone system. The latter undergoes demethylenation and recyclization into a novel hexahydrochromeno[2,3-c:3,4-c′]dipyrrole tetracyclic system on heating with hydrochloric acid.     

Synthesis of pyrano[2,3-<Emphasis Type="Italic">c</Emphasis>]pyrazoles by ionic liquids under green and eco-safe conditions

Optimization of a green approach to the synthesis of pyrano[2,3-c]pyrazoles based on the one-pot, four-component condensation via a domino Knoevenagel/Michael/cyclization sequence was investigated. This method involved the evaluation of the activity of several ionic liquids (ILs) in various solvents. This one-pot, four-component reaction revealed simplicity, higher yield and lower toxicity advantages over a corresponding three-component method. The effect of reaction parameters including the type and amount of catalyst, type of solvent, reaction temperature and time were studied with respect to yield of pyrano[2,3-c]pyrazoles. Catalyst recyclability and time-saving aspects of the reaction suggest that this method presents real alternatives over conventional reaction protocols.     

Organocatalyzed enantioselective synthesis of 6-amino-5-cyanodihydropyrano[2,3-c]pyrazoles

The first enantioselective synthesis of biologically active 6-amino-5-cyanodihydropyrano[2,3-c]pyrazoles has been achieved through a cinchona alkaloid-catalyzed tandem Michael addition and Thorpe-Ziegler type reaction between 2-pyrazolin-5-ones and benzylidenemalononitriles. The reaction may also be carried out in a three-component or a four-component fashion via the in situ formation of these two components from simple and readily available starting materials. The desired products were obtained in excellent yields with mediocre to excellent enantioselectivities (up to >99% ee).     

Synthesis of 2-(trifluoromethyl)-1,2-dihydro-4H-thieno[2,3-c]chromen-4-ones and 2-(trifluoromethyl)-4H-thieno[2,3-c]chromen-4-ones from 2-trifluoromethylchromones and ethyl mercaptoacetate

The redox reaction of 2-trifluoromethylchromones with ethyl mercaptoacetate in the presence of triethylamine results in the formation of 1,2-dihydrothieno[2,3-c]chromen-4-ones and diethyl 3,4-dithiadipate in high yields. Oxidation of the first compounds with nitrogen dioxide gave 1,2-dihydrothieno[2,3-c]chromen-3,4-diones which were converted into thieno[2,3-c]chromen-4-ones.     

Facile synthesis of novel CF3-substituted ring-fused furo[2,3-c]pyrazoles through Rh2(OAc)4 catalyzed [3+2] cycloaddition of 4-diazo-1-phenyl-3-(trifluoromethyl)-1H-pyrazol-5(4H)-one with aromatic alkynes

The Rh₂(OAc)₄ catalyzed [3+2] cycloaddition of 4-diazo-1-phenyl-3-(trifluoromethyl)-1H-pyrazol-5(4H)-one with aromatic alkynes was studied, and this protocol can be efficiently applied to the synthesis of the novel CF₃-substituted ring-fused furo[2,3-c]pyrazoles.     

Enantioselective access to tetrahydropyrano[2,3-c]pyrazoles via an organocatalytic domino Michael-hydroalkoxylation reaction

An asymmetric domino Michael-hydroalkoxylation reaction of trans-α-alkynyl-nitroolefins with N-arylpyrazolinones has been accomplished using a chiral bifunctional squaramide catalyst. Under the organocatalytic method, a broad range of tetrahydropyrano[2,3-c]pyrazoles with an exocyclic alkene at the C-6 position were prepared in high yields and excellent stereoselectivities. The presence of an exocyclic double bond and nitro group in the pyranopyrazoles provide a wide scope for further structural transformations.     

Reactivity of the Mitsunobu reagent toward 3-formylchromones: a strategy for the one-pot synthesis of chromeno[2,3-c]pyrazolines and chromeno[2,3-e]tetrazepines

The zwitterionic intermediates generated from dialkyl azodicarboxylates and triphenylphosphine displayed excellent reactivity toward 3-formylchromones to afford chromeno[2,3-c]pyrazolines and chromeno[2,3-e]tetrazepines.     

Synthesis of furo[2,3-c]-2,7-naphthyridine derivatives via domino heterocyclization reaction

2-Amino-4-cyanomethyl-6-dialkylamino-3,5-pyridinedicarbonitriles were found to react with substituted oxiranes yielding 5,6-diamino-8-dialkylamino-1,2-dihydrofuro[2,3-c]-2,7-naphthyridine-9-carbonitriles. The oxirane ring was shown to be opened selectively from the unsubstituted side and further cyclization occurred with participation of 3-CN, but not 5-CN of the starting pyridines. The furonaphthyridines obtained were converted into 2-dialkylamino-5-methyl-9,10-dihydro-4H-furo[2,3-c]pyrimido[4,5,6-ij]-2,7-naphthyridine-1-carbonitriles and 2-dialkylamino-5,6,9,10-tetrahydro-4H-spiro{furo[2,3-c]pyrimido[4,5,6-ij]-2,7-naphthyridine-5,1′-cyclohexane}-1-carbonitriles by treatment with acetic anhydride and cyclohexanone, respectively. The structure of prepared compounds was confirmed unambiguously by X-ray crystallographic study.     

Cross-condensation of derivatives of cyanoacetic acid and carbonyl compounds. Part 1: Single-stage synthesis of 1′-substituted 6-amino-spiro-4-(piperidine-4′)-2H,4H-pyrano[2,3-c]pyrazole-5-carbonitriles

To develop a method of synthesis of the potentially physiologically active compounds, 1′-substituted 6-amino-spiro-4-(piperidine-4′)-2H,4H-pyrano[2,3-c]pyrazoles, we studied the three-component condensation of substituted piperidin-4-ones, malononitrile and pyrazolin-5-ones. It was found that the electrochemical method of synthesis is more regioselective, the products of the reaction are analytically pure and do not require further recrystallization.     

Rapid Synthesis of Polyfunctionalized Pyrano[2,3-c]pyrazoles via Multicomponent Condensation in Room-Temperature Ionic Liquids

A highly efficient synthesis of 4H-pyrano[2,3-c]pyrazoles has been completed using four-component cyclocondensation of hydrazine monohydrate/phenyl hydrazine, ethyl acetoacetate, aldehydes, and malononitrile in the presence of L-proline and room-temperature ionic liquids.     

Photochemistry of 3H-furo[3,4-c]pyrazoles and 3H-thieno[3,4-c]pyrazoles

The first examples of 3H-furo[3,4-c]pyrazoles and 3H-thieno[3,4-c]pyrazoles were prepared in an attempt to isolate examples of cyclopropane-fused thiophenes and furans. Adducts of acetylenic ketones and 2-diazopropane were reacted with 10-camphorsulfonic acid or phosphorus pentasulfide to produce the title compounds. Photolysis of these compounds did not give the cyclopropane-fused products rather an unreported photochemical fragmentation was observed.     

Activated nitriles in heterocyclic synthesis. A novel synthesis of pyrazolo[1,5-a]pyrimidines and pyrano[2,3-c]pyrazoles

Several new pyrazolo[1,5-a]pyrimidines and pyrano[2,3-c]pyrazoles were synthesized viathe reaction of the cinnamonitrile derivatives 1a-c with 5-amino-3-phenylpyrazole ( 1 ), 3-amino-2-pyrazolin-5-one ( 2 ) and 3-amino-1-phenyl-2-pyrazolin-5-one ( 22 ).     

Novel fluoro-substituted benzo- and benzothieno fused pyrano[2,3-c]pyrazol-4(1H)-ones

A straightforward, two-step synthesis of fluoro substituted chromeno[2,3-c]pyrazol- and [1]benzothieno[2′,3′:5,6]pyrano[2,3-c]pyrazol-4(1H)-ones, respectively, is presented. Hence, treatment of 1-substituted or 1,3-disubstituted 2-pyrazolin-5-ones with fluoro substituted 2-fluorobenzoyl chlorides or 3-chloro-6-fluoro-1-benzothiophene-2-carbonyl chloride using calcium hydroxide in refluxing 1,4-dioxane gave the corresponding 4-aroylpyrazol-5-ols, which were cyclized into the fused ring systems. 5-Fluorochromeno[2,3-c]pyrazol-4(1H)-one was obtained upon treatment of the 1-(4-methoxybenzyl) protected congener with trifluoroacetic acid. Treatment of 5-fluorochromeno[2,3-c]pyrazol-4(1H)-ones with methylhydrazine afforded novel tetracyclic ring systems such as 2-methyl-7-phenyl-2,7-dihydropyrazolo[4′,3′:5,6]pyrano[4,3,2-cd]indazole. Detailed NMR spectroscopic investigations (¹H, ¹³C, ¹⁵N, ¹⁹F) with the obtained compounds were undertaken.