91565-80-9

Upstream product

• 213257-69-3 N-(2-methylphenyl)benzophenone hydrazone 
• 123-54-6 acetylacetone 
• 10199-63-0 1-(3,5-dimethyl-1H-pyrazol-1-yl)ethanone 
• 16419-60-6 2-Methylphenylboronic acid 
• 67-51-6 3,5-dimethyl-1H-pyrazole 
• 529-27-1 2-methylphenylhydrazine 
• 635-26-7 o-tolylhydrazine hydrochloride 
• 95-49-8 2-methylchlorobenzene 

Downstream Products

• 91768-95-5 3,5-dimethyl-4-thiocyanato-1-(o-tolyl)-1H-pyrazole 

Relevant academic research and scientific papers

Visible-light enabled C4-thiocyanation of pyrazoles by graphite-phase carbon nitride (g-C3N4)

Thiocyanation is an important and effective way to form C[sbnd]S bonds in organic synthetic methodology. Especially, thiocyanation of pyrazole attracts the attention of many researchers because sulfur-containing compounds are widely applied in many crucial fields such as organic materials, agrochemistry, nanotechnology, etc. Herein, we described A rapid metal- and additive-free method for C(sp2)-H thiocyanation of pyrazoles under visible light at room temperature by using a sustainable catalyst of graphite-phase carbon nitride (g-C3N4) and a thiocyanating agent of ammonium thiocyanate. The method presents many advantages, such as usage of eco-friendly photoredox catalyst, a wide range of substrates and a good yield of products, etc.

Oxone-DMSO Triggered Methylene Insertion and C(sp2)-C(sp3)-H-C(sp2) Bond Formation to Access Functional Bis-Heterocycles

Metal-free insertion of a methylene group was achieved for the construction of a new C(sp2)-C(sp3)-H-C(sp2) bond in order to prepare novel bis-heterocyclic scaffolds. The complete mechanistic investigations included experimental study and DFT calculations, and various symmetric and unsymmetric bis-pyrazoles as well as other pyrazole-based bis-heterocyclic molecules were prepared in moderate to high yields. Further modification of the bridged methylene group in the unsymmetric pyrazoles generated a chiral center to extend the scope of this method.

NSC 18725, a Pyrazole Derivative Inhibits Growth of Intracellular Mycobacterium tuberculosis by Induction of Autophagy

The increasing incident rates of drug-resistant tuberculosis (DR-TB) is a global health concern and has been further complicated by the emergence of extensive and total drug-resistant strains. Identification of new chemical entities which are compatible with first-line TB drugs, possess activity against DR-, and metabolically less active bacteria is required to tackle this epidemic. Here, we have performed phenotypic screening of a small molecule library against Mycobacterium bovis BCG and identified 24 scaffolds that exhibited MIC99 values of at least 2.5 μM. The most potent small molecule identified in our study was a nitroso containing pyrazole derivative, NSC 18725. We observed a significant reduction in viable bacilli load of starved Mycobacterium tuberculosis upon exposure to NSC 18725. The action of NSC 18725 was “synergistic” with isoniazid (INH) and “additive” with other drugs in our checkerboard assays. Structure-activity relationship (SAR) studies of the parent compound revealed that pyrazole derivatives without a functional group at fourth position lacked anti-mycobacterial activity in vitro. The derivative with para-chlorophenyl substitution at the first position of the pyrazole ring was the most active scaffold. We also demonstrate that NSC 18725 is able to induce autophagy in differentiated THP-1 macrophages. The induction of autophagy by NSC 18725 is the major mechanism for the killing of intracellular slow and fast-growing mycobacteria. Taken together, these observations support the identification of NSC 18725 as an antimycobacterial compound, which synergizes with INH, is active against non-replicative mycobacteria and induces autophagy in macrophages.

Application and developing of iron-doped multi-walled carbon nanotubes (Fe/MWCNTs) as an efficient and reusable heterogeneous nanocatalyst in the synthesis of heterocyclic compounds

Iron-doped multi-walled carbon nanotubes (Fe/MWCNTs) is an efficient, ecofriendly and reusable heterogeneous nanocatalyst for the one-pot synthesis of heterocyclic compounds including bis-spiro piperidines, piperidines, dihydro-2-oxopyrroles, pyrazoles and diazepines at room temperature with good to excellent yields. The heterogeneous nanocatalyst was fully characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD), inductively coupled plasma (ICP) and FT-IR analysis. Also, the structures of all prepared compounds were characterized by 1H NMR, 13C NMR, FT-IR, mass spectrometry (MS) and elemental analysis. The major advantages of these protocols are mild and green reaction conditions, short reaction times, clean reaction, operational simplicity, easy purification and good to excellent yields with the reusable heterogeneous nanocatalyst. The catalyst was ten recycled without significant loss of activity.

Copper-catalyzed C–N cross-coupling of arylboronic acids with N-acylpyrazoles

A copper-catalyzed C–N bond forming reaction of arylboronic acids and N-acylpyrazoles was developed. This procedure used N-acetyl protected pyrazoles as starting material instead of free pyrazoles (NH). The reaction worked under neutral conditions and did not require any base or ligand. The reaction showed good functional group tolerance.

Diazirines as potent electrophilic Nitrogen sources: Application to the synthesis of Pyrazoles

Even after more than 50 years since its discovery, the electrophilic potential of diazirines was never truly exploited. This longstanding limitation has been resolved. N-Monosubstituted diaziridines and hydrazones are obtained by nucleophilic additions. They release, under hydrolysis conditions, the corresponding monosubstituted hydrazines. The latter were converted to pyrazoles in high yields. The adamantanone can be recovered in 80-100% yields. This work demonstrates the potential of diazirines as electrophilic nitrogen sources with recoverable protecting groups.

BippyPhos: A single ligand with unprecedented scope in the Buchwald-Hartwig amination of (hetero)aryl chlorides

Over the past two decades, considerable attention has been given to the development of new ligands for the palladium-catalyzed arylation of amines and related NH-containing substrates (i.e., Buchwald-Hartwig amination). The generation of structurally diverse ligands, by research groups in both academia and industry, has facilitated the accommodation of sterically and electronically divergent substrates including ammonia, hydrazine, amines, amides, and NH heterocycles. Despite these achievements, problems with catalyst generality persist and access to multiple ligands is necessary to accommodate all of these NH-containing substrates. In our quest to address this significant limitation we identified the BippyPhos/[Pd(cinnamyl)Cl]2 catalyst system as being capable of catalyzing the amination of a variety of functionalized (hetero)aryl chlorides, as well as bromides and tosylates, at moderate to low catalyst loadings. The successful transformations described herein include primary and secondary amines, NH heterocycles, amides, ammonia and hydrazine, thus demonstrating the largest scope in the NH-containing coupling partner reported for a single Pd/ligand catalyst system. We also established BippyPhos/ [Pd(cinnamyl)Cl]2 as exhibiting the broadest demonstrated substrate scope for metal-catalyzed cross-coupling of (hetero)aryl chlorides with NH indoles. Furthermore, the remarkable ability of BippyPhos/[Pd(cinnamyl)Cl] 2 to catalyze both the selective monoarylation of ammonia and the N-arylation of indoles was exploited in the development of a new one-pot, two-step synthesis of N-aryl heterocycles from ammonia, ortho- alkynylhalo(hetero)arenes and (hetero) aryl halides through tandem N-arylation/hydroamination reactions. Although the scope in the NH-containing coupling partner is broad, BippyPhos/[Pd(cinnamyl)Cl]2 also displays a marked selectivity profile that was exploited in the chemoselective monoarylation of substrates featuring two chemically distinct NH-containing moieties.

Novel application of the palladium-catalyzed N-arylation of hydrazones to a versatile new synthesis of pyrazoles

A versatile synthesis of pyrazoles from aryl benzophenone hydrazones was demonstrated with a variety of 1,3-bifunctional substrates under acidic conditions. The obtained regioselectivity is consistent with transhydrazonation followed by subsequent cycliza