ChemInform Abstract: 1,3‐Dipolar Cycloaddition of Nitrile Imines with Functionalized Acetylenes: Regiocontrolled Sc(OTf)<sub>3</sub>‐Catalyzed Synthesis of 4‐ and 5‐Substituted Pyrazoles.

Bonini, Bianca F.; Franchini, Mauro Comes; Gentili, Denis; Locatelli, Erica; Ricci, Alfredo

doi:10.1002/chin.201003119

Cited by 2 publications

(2 citation statements)

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“…Experimental procedures and characteristic data for all synthesized compounds are given in the Supplementary Information [ 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 ].…”

Section: Methodsmentioning

confidence: 99%

Regioselective Cycloaddition of Nitrile Imines to 5-Methylidene-3-phenyl-hydantoin: Synthesis and DFT Calculations

Filkina

Baray

Белоглазкина

et al. 2023

IJMS

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Nitrile imine cycloaddition to hydantoins containing an exocyclic C=C double bond has been previously described in a very limited number of examples. In this work, regioselective synthesis of spiro-pyrazoline-imidazolidine-2,4-diones based on a 1,3-dipolar cycloaddition reaction of nitrile imines to 5-methylidene-3-phenyl-hydantoin have been proposed. It was found that, regardless of the nature of the aryl substituents at the terminal C and N atoms of the C-N-N fragment of nitrile imine (electron donor or electron acceptor), cycloaddition to the 5-methylidenhydantoin exocyclic C=C bond proceeds regioselectively, and the terminal nitrogen atom of the nitrile imine connects to the more sterically hindered carbon atom of the double bond, which leads to the formation of a 5-disubstituted pyrazoline ring. The observed cycloaddition regioselectivity was rationalized using DFT calculations of frontier molecular orbital interactions, global CDFT reactivity indices, and minimum energy paths.

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Section: Methodsmentioning

confidence: 99%

Regioselective Cycloaddition of Nitrile Imines to 5-Methylidene-3-phenyl-hydantoin: Synthesis and DFT Calculations

Filkina

Baray

Белоглазкина

et al. 2023

IJMS

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“…An approach that surely solved the problem of regioselectivity was the multicomponent synthesis illustrated in Scheme 1 b [ 22 ], but the method has limited applications due to the difficult preparation of reagents or use of closed reactors [ 23 ]. The 1,3-dipolar cycloaddition reaction between alkynes and nitrilimines generated in situ from hydrazonyl halides ( Scheme 1 c) provided tetrasubstituted Pzs in good yields without, however, the overcoming of very low regioselectivity [ 24 , 25 ].…”

Section: Introductionmentioning

confidence: 99%

Novel Regioselective Synthesis of 1,3,4,5-Tetrasubstituted Pyrazoles and Biochemical Valuation on F1FO-ATPase and Mitochondrial Permeability Transition Pore Formation

Algieri

Algieri²,

Costanzo

et al. 2023

Pharmaceutics

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An efficient, eco-compatible, and very cheap method for the construction of fully substituted pyrazoles (Pzs) via eliminative nitrilimine-alkene 1,3-dipolar cycloaddition (ENAC) reaction was developed in excellent yield and high regioselectivity. Enaminones and nitrilimines generated in situ were selected as dipolarophiles and dipoles, respectively. A deep screening of the employed base, solvent, and temperature was carried out to optimize reaction conditions. Recycling tests of ionic liquid were performed, furnishing efficient performance until six cycles. Finally, a plausible mechanism of cycloaddition was proposed. Then, the effect of three different structures of Pzs was evaluated on the F1FO-ATPase activity and mitochondrial permeability transition pore (mPTP) opening. The Pz derivatives’ titration curves of 6a, 6h, and 6o on the F1FO-ATPase showed a reduced activity of 86%, 35%, and 31%, respectively. Enzyme inhibition analysis depicted an uncompetitive mechanism with the typical formation of the tertiary complex enzyme-substrate-inhibitor (ESI). The dissociation constant of the ESI complex (Ki’) in the presence of the 6a had a lower order of magnitude than other Pzs. The pyrazole core might set the specific mechanism of inhibition with the F1FO-ATPase, whereas specific functional groups of Pzs might modulate the binding affinity. The mPTP opening decreased in Pz-treated mitochondria and the Pzs’ inhibitory effect on the mPTP was concentration-dependent with 6a and 6o. Indeed, the mPTP was more efficiently blocked with 0.1 mM 6a than with 1 mM 6a. On the contrary, 1 mM 6o had stronger desensitization of mPTP formation than 0.1 mM 6o. The F1FO-ATPase is a target of Pzs blocking mPTP formation.

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ChemInform Abstract: 1,3‐Dipolar Cycloaddition of Nitrile Imines with Functionalized Acetylenes: Regiocontrolled Sc(OTf)₃‐Catalyzed Synthesis of 4‐ and 5‐Substituted Pyrazoles.

Cited by 2 publications

References 1 publication

Regioselective Cycloaddition of Nitrile Imines to 5-Methylidene-3-phenyl-hydantoin: Synthesis and DFT Calculations

Regioselective Cycloaddition of Nitrile Imines to 5-Methylidene-3-phenyl-hydantoin: Synthesis and DFT Calculations

Novel Regioselective Synthesis of 1,3,4,5-Tetrasubstituted Pyrazoles and Biochemical Valuation on F1FO-ATPase and Mitochondrial Permeability Transition Pore Formation

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ChemInform Abstract: 1,3‐Dipolar Cycloaddition of Nitrile Imines with Functionalized Acetylenes: Regiocontrolled Sc(OTf)3‐Catalyzed Synthesis of 4‐ and 5‐Substituted Pyrazoles.

Cited by 2 publications

References 1 publication

Regioselective Cycloaddition of Nitrile Imines to 5-Methylidene-3-phenyl-hydantoin: Synthesis and DFT Calculations

Regioselective Cycloaddition of Nitrile Imines to 5-Methylidene-3-phenyl-hydantoin: Synthesis and DFT Calculations

Novel Regioselective Synthesis of 1,3,4,5-Tetrasubstituted Pyrazoles and Biochemical Valuation on F1FO-ATPase and Mitochondrial Permeability Transition Pore Formation

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ChemInform Abstract: 1,3‐Dipolar Cycloaddition of Nitrile Imines with Functionalized Acetylenes: Regiocontrolled Sc(OTf)₃‐Catalyzed Synthesis of 4‐ and 5‐Substituted Pyrazoles.