64123-72-4

Upstream product

• 1694-31-1 tert-butyl acetoacetate 
• 100-63-0 phenylhydrazine 
• 74-88-4 methyl iodide 
• 7152-15-0 ethyl 4-methyl-3-oxo-pentanoate 
• 42558-54-3 Methyl 4-methyl-3-oxopentanoate 
• 542-08-5 isopropyl acetoacetate 
• 59-88-1 phenylhydrazine hydrochloride 
• 34036-16-3 5-methyl-3-oxo-hexanoic acid ethyl ester 

Downstream Products

• 909250-34-6 5-(4-chloro-phenoxy)-3-isopropyl-1-phenyl-1H-pyrazole-4-carbaldehyde 
• 861435-79-2 5-(4-chloro-phenoxy)-3-isopropyl-1-phenyl-1H-pyrazole-4-carbaldehyde oxime 
• 1218782-30-9 4-hydroxy-3-isopropyl-1,5-diphenylpyrano[2,3-c]pyrazol-6-one 
• 1242100-46-4 1,4,5,6-tetrahydro-6-methyl-1,6-diphenyl-3-isopropyl-pyrano[2,3-c]pyrazole 
• 139347-69-6 4-Cyano-5-hydroxy-3-isopropyl-1-phenylpyrazole 
• 83957-87-3 3-isopropyl-2-methyl-1-phenyl-3-pyrazolin-5-one 

Relevant academic research and scientific papers

Enantioselective Synthesis of Spiropyrazolone-Fused Cyclopenta[ c]chromen-4-ones Bearing Five Contiguous Stereocenters via (3+2) Cycloaddition

An enantioselective synthesis of spiropyrazolone-fused cyclopenta[c]chromen-4-ones is demonstrated via a (3+2) cycloaddition reaction. The reactions of 3-homoacylcoumarins and α,β-unsaturated pyrazolones in the presence of the cinchona-alkaloid derived hy

Rhodium-Catalyzed [4+2] Annulation of N-Aryl Pyrazolones with Diazo Compounds To Access Pyrazolone-Fused Cinnolines

An efficient synthesis of novel dinitrogen-fused heterocycles such as pyrazolo[1,2-a]cinnoline derivatives have been accomplished by the rhodium(III)-catalyzed reaction of N-arylpyrazol-5-ones with α-diazo compounds. This reaction proceeds through a cascade C?H activation/intramolecular cyclization with a broad substrate scope. Furthermore, this protocol is successfully extended to the unusual phosphorus-containing α-diazo compounds and cyclic diazo compounds as the cross-coupling partners to deliver the two new kinds of pyrazolo[1,2-a]cinnolinones. The control experiments were performed to reveal insight into the mechanism of this reaction, involving reversible C?H activation, migratory insertion of the diazo compound, and cascade cyclization as the key steps of the transformation. Moreover, gram-scale synthesis and further transformation of the target product demonstrate the synthetic utility of the present protocol.

Catalytic Asymmetric Addition of Diorganozinc Reagents to Pyrazole-4,5-Diones and Indoline-2,3-Diones

The catalytic enantioselective diorganozinc additions to cyclic diketones including pyrazolin-4,5-diones and isatins have been developed. In the presence of morpholine-containing chiral amino alcohol ligand, the corresponding chiral cyclic tertiary alcohols were produced in good to excellent yields (up to 97 %) and enantioselectivities (up to 95 % ee). The notable feature of this protocol includes its mild reaction conditions, Lewis acid additives free and broad functional group tolerance.

Diversity-Oriented Synthesis of Spiropentadiene Pyrazolones and 1 H-Oxepino[2,3- c]pyrazoles from Doubly Conjugated Pyrazolones via Intramolecular Wittig Reaction

An efficient method for the diversity-oriented synthesis of spiropentadiene pyrazolones and 1H-oxepino[2,3-c]pyrazoles is reported. The methodology attributes O-acylation of phosphorus zwitterions which were formed by a tandem phospha-1,6-addition of PBu3 to α,β,γ,δ-unsaturated pyrazolones, further generating betaine intermediates that preferentially resulted in the aforementioned cyclic products in a diversity-oriented manner. The mechanistic investigations revealed that formation of the betaines is the key step to provide the products via an intramolecular Wittig reaction or an unprecedented δ-C-acylation/cyclization/Wittig reaction.

Organophosphane-catalyzed direct β-acylation of 4-arylidene pyrazolones and 5-arylidene thiazolones with acyl chlorides

An efficient method for the direct β-acylation of arylidene pyrazolones and thiazolones with acyl chlorides in the presence of a base catalyzed by organophosphanes is reported. A variety of functionalized 4-arylidene pyrazolone and 5-arylidene thiazolone derivatives were prepared under metal-free and mild conditions via a tandem phospha-Michael addition/O-acylation/intramolecular cyclization/rearrangement sequence. Our mechanistic investigations revealed that the reaction is highly stereospecific to provide exclusively cis-isomers, and the methodology can also be scaled up with similar efficacy.

Synthesis and cytotoxic evaluation of some substituted 5-pyrazolones and their urea derivatives

In this paper, a series of new substituted-5-pyrazolones were first synthesized, then formulated by the Vilsmeier–Haack reaction to obtain substituted-4-carbaldehyde-5-pyrazolones. In the final step, when urea was reacted with formulated pyrazolones, we found that, instead of the C=N bond in azomethine form, the compounds tautomerized to form a series of novel pyrazole-4ylidenemethylurea structures. The structures of these compounds were elucidated by FTIR, 1H, 13C NMR, LC-MS/MS, and elemental analysis methods. The cytotoxic and antioxidant effects of substituted 5-pyrazolones and their pyrazolone-urea derivatives were investigated in metastatic A431 and noncancerous HaCaT human keratinocytes by a mitochondrial activity test. The effects of the compounds on the migration of cancerous and noncancerous cell lines were investigated by using a cell scratch assay. The General Linear Model, Statistical Package for Social Sciences (SPSS v26) was used to determine if there was a statistically significant difference between the control and the treatment groups. Four of the nine compounds showed an antioxidant effect. All 5-pyrazolone-urea compounds showed higher toxicity (p 0.05) in cancerous A431 cells compared to noncancerous cells at all time points. All compounds also showed a biphasic hormetic effect. Four of the nine compounds inhibited cell migration.

Metal-Free Direct C–H Thiolation and Thiocyanation of Pyrazolones

Metal-free approach for direct C–H thiolation and thiocyanation of N-substituted pyrazolones with disulfides and thiocyanate salts, respectively, are developed. These reactions allow the C–S bond coupling to proceed effectively under mild conditions, providing useful and convenient methods for preparation of a series of 4-thio-substituted pyrazolone analogues, which have potential applications in organic, medicinal and material chemistry. Preliminary mechanistic investigation suggested that radical processes are likely to involve in these transformations.

DABCO-catalyzed silver-promoted direct thiolation of pyrazolones with diaryl disulfides

A highly efficient protocol for a direct thiolation of N-substituted pyrazolones with diaryl disulfides is described. Using a combination of DABCO and silver(i) acetate, the C-S bond formation proceeds smoothly at room temperature under mild and easy to handle conditions. This synthetic strategy offers a convenient and direct modification of antipyrine and other pyrazolone substrates, giving a series of aryl sulfide-substituted pyrazolone products in moderate to excellent yields.

Dibromination of 5-pyrazolones and 5-hydroxypyrazoles via dibromoisocyanuric acid

(Chemical Equation Presented) A safe and efficient method was developed for the dibromination of pyrazolones and 5-hydroxypyrazoles by use of dibromoisocyanuric acid (DBI). The reaction gave the corresponding dibrominated pyrazolones in excellent yields (≥91%).

Multicomponent reactions of 1,3-disubstituted 5-pyrazolones and formaldehyde in environmentally benign solvent systems and their variations with more fundamental substrates

Many multicomponent reactions (MCRs) of 1,3-disubstituted 5-pyrazolones and formaldehyde were developed in environmentally benign solvent systems. Styrenes, vinylferrocene and 2-phenylindoles could easily react, under solvent-free conditions or in glycerol solvent, with 1,3-disubstituted 5-pyrazolones and paraformaldehyde in the absence of any catalyst to afford a variety of complex skeletons in moderate to excellent yields. Particularly, these MCRs are proved to be combinable with the synthesis of 1,3-disubstituted 5-pyrazolones from phenylhydrazines and β-ketone esters in glycerol or a carboxylic acid-functionalized ionic liquid, [MIm-CO2H]BF 4. Therefore, some two-step sequential reactions of phenylhydrazines, β-ketone esters, formaldehyde and styrenes or indoles were developed for the first time. All these MCRs were conducted in environmentally benign solvent systems that not only minimize generation of wastes but also simplify the work-up procedure.