Palladium‐catalyzed cyclization of β‐bromo‐α,β‐unsaturated ketones with arylhydrazines leading to 3‐substituted 1‐aryl‐1 H‐pyrazoles

β‐Bromo‐α,β‐unsaturated ketones are condensed with arylhydrazines to form hydrazones, which are in situ intramolecularly cyclized into 3‐substituted 1‐aryl‐1 H‐pyrazoles under a catalytic system of Pd(OAc)₂/1,3‐bis(diphenylhosphino)propane (dppp)/NaO^tBu. Copyright © 2012 John Wiley & Sons, Ltd.     

Sequential SNAr Reaction/Suzuki–Miyaura Coupling/C−H Direct Arylations Approach for the Rapid Synthesis of Tetraaryl‐Substituted Pyrazoles

A rapid synthesis of 1,3,4,5‐tetraaryl‐substituted pyrazoles has been achieved through a sequence of S_NAr reaction/Suzuki–Miyaura coupling/Pd‐catalyzed direct arylations that used 3‐iodo‐1H‐pyrazole as a scaffold. Pyrazoles with four different aryl groups were synthesized in a straightforward manner with no extra synthetic steps, such as protection/deprotection or the introduction of activating/directing groups, using readily available substrates and reagents. The developed synthetic approach enabled the structurally diverse synthesis of multiaryl‐substituted pyrazoles without using a glovebox technique.     

A Facile Synthesis of Some New 1‐Benzothiazolyl‐3‐aryl/Hetaryl‐5‐(3‐aryl‐1‐phenyl‐4‐pyrazolyl) Pyrazoles and Their Antimicrobial Activity

Some new derivatives of 1‐benzothiazolyl‐3‐aryl/hetaryl‐5‐(3‐aryl‐1‐phenyl‐4‐pyrazolyl) pyrazoles were synthesized by the cyclocondensation of 1‐aryl/hetaryl‐3‐(3‐aryl‐1‐phenyl‐1H‐pyrazole‐4‐yl)prop‐2‐en‐1‐ones (pyrazolyl chalcones) and 6‐substituted‐2‐hydrazinobenzothiazoles.     

Synthesis of 5‐Aryl‐3‐(methylsulfanyl)‐1H‐pyrazoles via Three‐Component Reaction of 1,1‐Bis(methylsulfanyl)‐2‐nitroethene,Aromatic Aldehydes,and Hydrazine

An efficient approach for the preparation of functionalized 5‐aryl‐3‐(methylsulfanyl)‐1H‐pyrazoles 2 is described. This three‐component reaction between benzaldehydes 1 , NH₂NH₂?H₂O, and 1,1‐bis(methylsulfanyl)‐2‐nitroethene proceeds in EtOH under reflux conditions in good‐to‐excellent yields. The structures of 2 were corroborated spectroscopically (IR, ¹H‐ and ¹³C‐NMR, and EI‐MS). A plausible mechanism for this type of reaction is proposed (Scheme 2).     

Synthesis and Antimicrobial Activities of Novel 2‐[substituted‐1H‐pyrazol‐4‐yl] Benzothiazoles,Benzoxazoles, and Benzimidazoles

In an endeavor to find a new class of antimicrobial agents, a series of novel substituted benzimidazole, benzoxazole, and benzothiazole derivatives 6 containing pyrazole moiety have been synthesized by reaction of 3‐aryl‐4‐formyl pyrazole 4 with substituted phenylenediamine or o‐aminophenol or o‐aminothiophenol 5 . Reaction of phenyl hydrazine or 2‐hydrazinopyridine 1 with substituted acetophenones 2 gave the corresponding hydrazones 3 , which on Vilsmeier–Haack reaction with POCl₃–DMF gave substituted 3‐aryl‐4‐formyl pyrazoles 4 . All final compounds 6a , 6b , 6c , 6d , 6e , 6f , 6g , 6h , 6i , 6j , 6k were evaluated for in vitro antibacterial activities against Escherichia coli and Staphylococcus aureus strains and in vitro antifungal activity against Candida albicans and Aspergillus niger strains by using serial dilution method. The antimicrobial activities were expressed as the minimum inhibitory concentration in µg/mL. The compound containing benzimidazole and benzoxazole moiety gave better antibacterial and antifungal activities than benzothiazole compounds.     

NH‐Heterocyclic Aryliodonium Salts and their Selective Conversion into N1‐Aryl‐5‐iodoimidazoles

The synthesis of N‐arylimidazoles substituted at the sterically encumbered 5‐position is a challenge for modern synthetic approaches. A new family of imidazolyl aryliodonium salts is reported, which serve as a stepping stone on the way to selective formation of N1‐aryl‐5‐iodoimidazoles. Iodine acts as a “universal” placeholder poised for replacement by aryl substituents. These new λ³‐iodanes are produced by treating the NH‐imidazole with ArI(OAc)₂, and are converted to N1‐aryl‐5‐iodoimidazoles by a selective copper‐catalyzed aryl migration. The method tolerates a variety of aryl fragments and is also applicable to substituted imidazoles.     

One‐Pot Synthesis of Functionalized 3‐Aryl‐1‐phenyl‐1H‐pyrazoles from Hydrazonoyl Chlorides and Acetylenic Esters in the Presence of Ph3P

The zwitterionic 1 : 1 intermediates generated by addition of Ph₃P to acetylenic esters is trapped by 1‐[(aryl)chloromethylene]‐2‐phenylhydrazines (=N‐phenylarenecarbohydrazonoyl chlorides) to yield functionalized 3‐aryl‐1‐phenyl‐1H‐pyrazoles in good yields.     

Synthesis and Characterization of 11‐Amino‐3‐methoxy‐8‐substituted‐12‐aryl‐8,9‐dihydro‐7H‐chromeno[2,3‐b]quinolin‐10(12H)‐one Derivatives

A series of 2‐amino‐7‐methoxy‐4‐aryl‐4H‐chromene‐3‐carbonitrile compounds 2 were obtained by condensation of 3‐methoxyphenol with β‐dicyanostyrenes 1 in absolute ethanol containing piperidine. The intermediate enamines 3 were prepared by compounds 2 with 5‐substituted‐1,3‐cyclohexanedione using p‐toluenesuflonic acid (TsOH) as catalyst. The title compounds 11‐amino‐3‐methoxy‐8‐substituted‐12‐aryl‐8,9‐dihydro‐7H‐chromeno[2,3‐b]quinolin‐10(12H)‐one 4 were synthesized by cyclization of the intermediate enamines 3 in THF with K₂CO₃ /Cu₂Cl₂ as catalyst. The structures of all compounds were characterized by elemental analysis, IR, MS, and ¹H NMR spectra. The crystal structure of compound 4i was determined by single‐crystal X‐ray diffraction analysis.     

Novel Approach for Rapid and Efficient Synthesis of 2‐(3‐(4‐Aryl)‐1‐isonicotinoyl‐4,5‐dihydro‐1H‐pyrazol‐4‐yl)‐3‐phenylthiazolidin‐4‐one Derivatives and Screened Their Antimicrobial Activity

A series of compounds, viz. 2‐(3‐(4‐aryl)‐1‐isonicotinoyl‐4,5‐dihydro‐1H‐pyrazol‐4‐yl)‐3‐phenylthiazolidin‐4‐one 4 ( a – n ), have been synthesized by reaction of 3 ( a – n ) with thioglycolic acid in the presence of zinc chloride. Compounds 3 ( a – n ) have been synthesized by amination of formylated pyrazoles 2 ( A – B ), which were synthesized by formylation of 1 ( A – B ) by Vilsmeier–Haack reagent (POCl₃/DMF). Compounds 1 ( A – B ) were synthesized by condensation of hydrazide and substituted acetophenones under conventional method and microwave irradiation method. These compounds were identified on the basis of melting point range, Rf values, infrared, ¹H NMR, and mass spectral analysis. These compounds were evaluated for their in vitro antimicrobial activity, and their minimum inhibitory concentration was determined. Among them, compound 4b and compound 4l possess appreciable antimicrobial and antifungal activities. Antibacterial activity results showed that compounds containing electron‐withdrawing groups were more active than compounds containing electron‐releasing groups.     

Regiospecific one‐pot synthesis of new trifluoromethyl substituted heteroaryl pyrazolyl ketones

A convenient and general method for the regiospecific synthesis of three novel series of 1‐(2‐thenoyl)‐, 1‐(2‐furoyl)‐ and 1‐(isonicotinoyl)‐3‐alkyl(aryl)‐5‐hydroxy‐5‐trifluoromethyl‐4,5‐dihydro‐1H‐pyrazoles, in good yields (53 – 91 %), from the cyclocondensation reactions of 1,1,1‐trifluoro‐4‐alkoxy‐4‐alkyl(aryl)‐but‐3‐en‐2‐ones, where alkyl = H and Me; aryl = ‐C₆H₅, 4‐CH₃C₆H₄, 4‐CH₃OC₆H₄, 4‐FC₆H₄, 4‐ClC₆H₄, 4‐BrC₆H₄, 4‐NO₂CgH₄ with 2‐thiophenecarboxylic hydrazide, furoic hydrazide and isonicotinic acid hydrazide, respectively, is reported. Subsequently dehydration reaction of phenyl substituted 2‐pyrazolines with P₂O₅ furnished the corresponding 1H‐pyrazoles as mixture of regioisomers and in low yields (35 – 36 %).     

Microwave‐Assisted Synthesis of Novel 2,4‐Dihydro‐5‐[4‐(trifluoromethyl)phenyl]‐3H‐1,2,4‐triazol‐3‐ones and Potentiometric Determination of Their pKa in Nonaqueous Solvents

The novel 4‐amino‐ or 4‐aryl‐substituted 2,4‐dihydro‐5‐[(4‐trifluoromethyl)phenyl]‐3H‐1,2,4‐triazol‐3‐ones 3a – 3g were synthesized by reaction of N‐(ethoxycarbonyl)‐4‐(trifluoromethyl)benzenehydrazonic acid ethyl ester ( 2 ) and primary amines or hydrazine by microwave irradiation. Compounds 3a – 3g were potentiometrically titrated with tetrabutylammonium hydroxide (Bu₄NOH) in four nonaqueous solvents, i.e., ⁱPrOH, ^tBuOH, MeCN, and N,N‐dimethylformamide (DMF). Also half‐neutralization potential values and the corresponding pK_a values were determined in all cases.     

Design,Synthesis, and Herbicidal Activities of 3‐Aryl‐4‐substituted‐5‐[3‐(trifluoromethyl)phenoxy]‐1,2,4‐triazoles

In order to find novel bleaching herbicide lead compounds, a series of novel 3‐aryl‐4‐substituted‐5‐[3‐(trifluoromethyl)phenoxy]‐1,2,4‐triazoles were designed and synthesized by the multi‐step reactions. N‐(Arylformamido)phenylthioureas undergo ring closure in the presence of sodium hydroxide to generate 3‐aryl‐4‐substituted‐4H‐[1,2,4]triazol‐5‐thiols 1 , which reacted with methyl sulfate in the presence of K₂CO₃ to give 3‐aryl‐5‐methylsulfanyl‐4‐substituted‐4H‐[1,2,4]triazoles 2 . The target compounds 4 were synthesized by the oxidation of 2 in the presence of H₂O₂ and Na₂WO₄, followed by the substitution with 3‐(trifluoromethyl)phenol in moderate to good yields. Their structures were confirmed by IR, ¹H NMR, EI–MS, and elemental analyses. The preliminary bioassay indicated that some of them displayed moderate to good selective herbicidal activity against Brassica campestris L at the concentration of 100 µg/mL. Compounds 4c and 4i possessed 75.0% and 82.6% inhibition against Brassica campestris L at the concentration of 100 µg/mL. However, the target compounds 4 showed weak herbicidal activity against Echinochloa crus‐galli at the concentration of 100 and 10 µg/mL.     

Facile synthesis of alkynyl‐, aryl‐ and ferrocenyl‐substituted pyrazoles via Sonogashira and Suzuki–Miyaura approaches

A concise and efficient synthesis of densely substituted novel pyrazoles with alkynyl, aryl and ferrocenyl functionalities is reported, providing a platform for biological studies. The general strategy involves Sonogashira and Suzuki–Miyaura cross‐coupling reactions of easily obtainable 5‐ferrocenyl/phenyl‐4‐iodo‐1‐phenylpyrazoles with terminal alkynes and boronic acids, respectively. The starting 4‐iodopyrazoles were synthesized by electrophilic cyclization of α,β‐alkynic hydrazones with molecular iodine. Sonogashira reactions have been achieved by employing 5 mol% PdCl₂(PPh₃)₂, 5 mol% CuI, excess Et₃N and 1.2 equiv. of terminal alkyne, relative to 4‐iodopyrazole, in tetrahydrofuran at 65 °C, while Suzuki–Miyaura reactions have been accomplished using 5 mol% PdCl₂(PPh₃)₂ and 1.4 equiv. of both boronic acid/ester and KHCO₃, with respect to 4‐iodopyrazole, in 4:1 dimethylformamide–H₂O solution at 110 °C. Both Sonogashira and Suzuki–Miyaura coupling reactions have proven effective for the synthesis of alkynyl‐, aryl‐ and ferrocenyl‐substituted pyrazoles and demonstrated good tolerance to a diverse range of substituents, including electron‐donating and electron‐withdrawing groups. These coupling approaches could allow for the rapid construction of a library of functionalized pyrazoles of pharmacological interest. Copyright © 2016 John Wiley & Sons, Ltd.     

Characterization of 4,5‐Dihydro‐1H‐Pyrazole Derivatives by 13C NMR Spectroscopy

The ¹³ C NMR resonances of 19 1‐acyl‐3‐(2‐nitro‐5‐substitutedphenyl)‐4,5‐dihydro‐1H‐pyrazoles, and 19 1‐acyl‐3‐(2‐amino‐5‐substituted)‐4,5‐dihydro‐1H‐pyrazoles, were completely assigned using the concerted application of one‐ and two‐dimensional NMR experiments (DEPT, gs‐HSQC and gs‐HMBC). Copyright © 2012 John Wiley & Sons, Ltd.     

One‐pot synthesis of aryl and heteroaroyl‐substituted hydroxypyrazolines from the reactions of β‐alkoxyvinyl trichloromethyl ketones with heteroarylhydrazides

The one‐step regiospecific synthesis of a novel series of 10 trichloromethyl‐, aryl‐, and heteroaroyl‐substituted 5‐hydroxy‐2‐pyrazolines affords 1‐(2‐thenoyl)‐, 1‐(2‐furoyl)‐, and 1‐(isonicotinoyl)‐3‐aryl‐5‐hydroxy‐5‐trichloromethyl‐4,5‐dihydro‐1H‐pyrazoles in 63–92% yields from the cyclocondensation reactions of 1,1,1‐trichloro‐4‐methoxy‐4‐aryl‐3‐buten‐2‐ones (where aryl substituents are –C₆H₅, 4‐CH₃C₆H₄, 4‐OCH₃C₆H₄, 4‐FC₆H₄, 4‐ClC₆H₄, 4‐BrC₆H₄) with 2‐thiophenecarboxylic hydrazide, furoic hydrazide, and isonicotinic acid hydrazide, respectively. Dehydration reaction of two 2‐pyrazolines with P₂O₅ furnished the corresponding 1H‐pyrazoles in low yields (21–29%). © 2006 Wiley Periodicals, Inc. Heteroatom Chem 17:685–691, 2006; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20261     

3‐Benzyl‐2‐(4‐fluorophenyl)‐1,3‐thiazolidin‐4‐one

The title compound, C₁₆H₁₄FNOS, crystallizes with Z′ = 2 in the space group P2₁/c. In one of the two independent molecules, the heterocyclic ring is effectively planar, but in the other molecule this ring adopts an envelope conformation. The molecules are weakly linked by two C—H...O hydrogen bonds to form C₂²(14) chains. Comparisons are made with some symmetrically substituted 2‐aryl‐3‐benzyl‐1,3‐thiazolidin‐4‐ones.     

1,3‐Dipolar Cycloadditions of Ethyl 2‐Diazo‐3,3,3‐trifluoropropanoate to Alkynes and [1,5] Sigmatropic Rearrangements of the Resulting 3H‐Pyrazoles: Synthesis of Mono‐, Bis‐ and Tris(trifluoromethyl)‐Substituted Pyrazoles

The 1,3‐dipolar cycloadditions of ethyl 2‐diazo‐3,3,3‐trifluoropropanoate with electron‐rich and electron‐deficient alkynes, as well as the van Alphen? Hüttel rearrangements of the resulting 3H‐pyrazoles were investigated. These reactions led to a series of CF₃‐substituted pyrazoles in good overall yields. Phenyl‐ and diphenylacetylene proved to be unreactive, but, at high temperature, the diazoalkane and phenylacetylene furnished a cyclopropene derivative. As expected, the 1,3‐dipolar cycloaddition to the ynamine occurred much faster than those to electron‐deficient alkynes. With one exception, all cycloadditions proceeded with excellent regioselectivities. The [1,5] sigmatropic rearrangement of the primary 3H‐pyrazoles provided products with shifted acyl groups; products resulting from the migration of a CF₃ group were not detected. In agreement with literature reports, this rearrangement occurs faster with 3H‐pyrazoles bearing electron‐withdrawing substituents.     

Synthesis of some new 1‐acyl‐5‐aryl‐3‐(5‐methyl‐1‐p‐tolyl‐1H‐1,2,3‐triazol‐4‐yl)‐4,5‐dihydro‐1H‐pyrazole

Some new compounds (E)‐3‐aryl‐1‐(5‐methyl‐1‐p‐tolyl‐1H‐1,2,3‐triazol‐4‐yl)‐prop‐2‐en‐1‐ones 5a–e were prepared by 1‐(5‐methyl‐1‐p‐tolyl‐1H‐1,2,3‐triazol‐4‐yl)‐ethanone and various aromatic aldehydes. Then one pot reaction was happened by compounds 5a–e with hydrazine hydrate in acetic acid or propionic acid, respectively, to give the title compounds 1acyl‐5‐aryl‐3‐(5‐methyl‐1‐p‐tolyl‐1H‐1,2,3‐triazol‐4‐yl)‐4,5‐dihydro‐1H‐pyrazoles 6a–i . All structures were established by MS, IR, CHN, ¹H‐NMR and ¹³C‐NMR spectral data. J. Heterocyclic Chem., (2012).     

Synthesis and Structures of N‐Alkyl‐1,13‐dimethoxychromeno‐ [2,3,4‐kl]acridinium Salts: The Missing Azaoxa[4]helicenium

Helical structures are interesting due to their inherent chirality. Helicenium ions are triarylmethylium structures twisted into configurationally stable helicenes through the introduction of two heteroatom bridges between the three aryl substituents. Of the configurationally stable [4]helicenium ions, derivatives with sulfur, oxygen and nitrogen bridges have already been synthesised. However, one [4]helicenium ion has proven elusive, until now. We present herein the first synthesis of the 1,13‐dimethoxychromeno[2,3,4‐kl]acridinium (DMCA⁺) [4]helicenium ion. A series of six differently N‐substituted DMCA⁺ ions as their hexafluorophosphate salts are reported. Their cation stability was evaluated and it was found that DMCA⁺ is ideally suited as a phase‐transfer catalyst with a pK_R+ of 13.0. The selectivity of nucleophilic addition to the central carbon atom of DMCA⁺ has been demonstrated with diastereotopic ratios of up to 1:10. The single‐crystal structures of several of the DMCA⁺ salts were determined, and structural differences between N‐aryl‐ and N‐alkyl‐substituted cations were observed. The results of a comparative study of the photophysics of the [4]helicenium ions are presented. DMCA⁺ is found to be a potent red‐emitting dye with a fluorescence quantum yield of 20 % in apolar solvents and a fluorescence lifetime of 12 ns. [4]Helicenium ions, including DMCA⁺, all suffer from solvent‐induced quenching, which reduces the fluorescence quantum yields significantly (?_fl<5 %) in polar solvents. A difference in photophysical properties is observed between N‐aryl‐ and N‐alkyl‐substituted DMCA⁺, which has tentatively been attributed to a difference in molecular conformation.     

Microwave Induced Synthesis of 3‐Aryl‐6‐(6‐/8‐substituted 4‐chloroquinoline‐3‐yl) ‐ s ‐triazolo [3,4‐b] −1,3,4‐thiadiazoles

The condensation of 4‐amino‐3‐aryl‐5‐mercapto‐1, 2, 4‐triazoles (1a‐f) with 6‐/8‐substituted 1,4‐dihydro‐4‐oxo‐quinoline‐3‐carboxylic adds (2a‐d) in the presence of phosphorus oxychloride on refluxng or under microwave irradiation gave twenty four novel 3‐aryl‐6‐ (6‐/8‐substituted 4‐chloroquinoline‐3‐yl)‐s‐triazolo[3,4‐b]‐1, 3,4‐thiadiazoles (4a‐x), Considerable increase in the reaction rate has been observed with improved yields under microwave irradiation. The structures of the compounds synthesized were determined by elemental analyses, IR, ¹H NMR and MS spectra. Their spectral properties and the reaction mechanism were also discussed. The preliminary biological test showed that some of compounds bad moderate antibacterial activities.