Diffusion mixing with a volatile tertiary amine as a very efficient technique for 1,3-dipolar cycloaddition reactions proceeding <i>via</i> dehydrohalogenation of stable precursors of reactive dipoles

Shybanov, Dmitry E.; Filkina, Maria E.; Kukushkin, Maxim E.; Grishin, Yu. K.; Roznyatovsky, Vitaly A.; Зык, Н. В.; Белоглазкина, Е. К.

doi:10.1039/d2nj03756d

Cited by 8 publications

(8 citation statements)

References 45 publications

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“… A total of 1,3-dipolar cycloaddition reactions of nitrile imines to ( a ) 5-methylidene hydantoin [ 11 , 14 ]; ( b ) 5-arylidene thiohydantoins [ 10 , 13 ]; and ( c ) 5-arylimino hydantoins (this work). …”

Section: Figures Schemes and Tablesmentioning

confidence: 99%

“…To obtain nitrile imines, we used hydrazonoyl chlorides 3a-g (Figure 4), which are readily available by the method [11]. Our laboratory has recently developed the so-called "diffusion reagent mixing technique", which allows the gradual generation of 1,3-dipoles in solution and effectively suppresses the processes of their unwanted dimerization [14]. In many cases, the diffusion mixing technique makes it possible to significantly increase the yield of the target [3+2]-cycloaddition products and is especially effective in cases of interaction with highly reactive dipoles.…”

Section: 3-dipolar Cycloaddition Of Nitrile Imines To 2-thioxoimidazo...mentioning

confidence: 99%

“…Figure 2. A total of 1,3-dipolar cycloaddition reactions of nitrile imines to (a) 5-methylidene hydantoin [11,14]; (b) 5-arylidene thiohydantoins [10,13]; and (c) 5-arylimino hydantoins (this work). Hydantoins exhibit a wide range of biological activity, among which antitumor, antibacterial, anticonvulsant, antiepileptic, and antiarrhythmic properties, as well as action as muscle relaxants, can be distinguished [9].…”

Section: Introductionmentioning

confidence: 99%

“…Figure 2. A total of 1,3-dipolar cycloaddition reactions of nitrile imines to (a) 5-methylidene hydantoin [11,14]; (b) 5-arylidene thiohydantoins [10,13]; and (c) 5-arylimino hydantoins (this work). [11,14]; (b) 5-arylidene thiohydantoins [10,13]; and (c) 5-arylimino hydantoins (this work).…”

Section: Introductionmentioning

confidence: 99%

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[3+2]-Cycloaddition of Nitrile Imines to Parabanic Acid Derivatives—An Approach to Novel Spiroimidazolidinediones

Kuznetsova,

Tkachenko,

Petrovskaya

et al. 2023

IJMS

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Approximately 1,3-Dipolar cycloaddition of imidazolidine derivatives containing exocyclic double bonds is a convenient method of creating spiro-conjugated molecules with promising anticancer activity. In this work, the derivatives of parabanic acid (2-thioxoimidazolidine-4,5-diones and 5-aryliminoimidazolidine-2,4-diones) were first investigated as dipolarophiles in the reactions with nitrile imines. The generation of nitrile imines was carried out either by the addition of tertiary amine to hydrazonoyl chlorides «drop by drop» or using the recently proposed diffusion mixing technique, which led to ~5–15% increases in target compound yields. It was found that the addition of nitrile imines to C=S or C=N exocyclic double bonds led to 1,2,4-thiazolines or triazolines and occurred regioselectively in accordance with the ratio of FMO coefficients of reactants. The yield of the resulting spiro-compound depended on the presence of alkyl substituents in the nitrile imine structure and was significantly decreased in reactions with imines with strong electron donor or electron-withdrawing groups. Some of the obtained compounds showed reasonable in vitro cytotoxicity. IC50 values were calculated for HCT116 (colon cancer) cells using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) test.

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Section: Figures Schemes and Tablesmentioning

confidence: 99%

Section: 3-dipolar Cycloaddition Of Nitrile Imines To 2-thioxoimidazo...mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…Figure 2. A total of 1,3-dipolar cycloaddition reactions of nitrile imines to (a) 5-methylidene hydantoin [11,14]; (b) 5-arylidene thiohydantoins [10,13]; and (c) 5-arylimino hydantoins (this work). [11,14]; (b) 5-arylidene thiohydantoins [10,13]; and (c) 5-arylimino hydantoins (this work).…”

Section: Introductionmentioning

confidence: 99%

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[3+2]-Cycloaddition of Nitrile Imines to Parabanic Acid Derivatives—An Approach to Novel Spiroimidazolidinediones

Kuznetsova,

Tkachenko,

Petrovskaya

et al. 2023

IJMS

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“…In recent work of Yavari [ 17 ], the cycloaddition of nitrile imines to 5-arylmethylene-2-thiohydantoins, leading to the formation of a mixture of two products containing a 5-substituted pyrazoline fragment and a 1,2,4-thiazoline fragment, respectively, was shown. The cycloaddition of nitrile imines to hydantoins containing a 1,1-disubstituted exocyclic carbon-carbon double bond was first described in previous work of our scientific group [ 18 ]. In the literature there are also a few examples of the addition of nitrile imines to exocyclic double C=C bonds of other types [ 19 , 20 , 21 ].…”

Section: Introductionmentioning

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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Advances in the Synthesis of Heterocycles with Two and Three Heteroatoms using Hydrazonoyl Halides

Yamaletdinova,

Gataullin

2024

Helvetica Chimica Acta

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The review covers the results of studies published in the literature on the use of hydrazonoyl halides in the synthesis of five‐ (pyrazoles, thiazoles, triazoles, oxa‐ and thiadiazoles), six‐ (oxa‐ and thiadiazines, indazoles, pyridazines, pyrazines, tetrazines) or seven‐membered (benzotriazepine) heterocycles. In the formation of these heterocycles, the main intermediate stage of the reaction is the in situ generation of nitrilimine, which enters into a cycloaddition reaction with substituted acetylenes (including in situ generated benzynes, naphthynes), allenes, activated olefins, anthranilic acid derivatives, organosulfur compounds (mercaptoaldehydes, mercaptocarboxylic acids ) or with fused heterocycles. Examples are given of the formation of heterocycles by replacing the halogen atom from a hydrazonoyl halide molecule with a nucleophilic group, followed by exhaustive intramolecular cyclization into the target compound. There are discussions of reactions in which the cycloaddition of the nitrilimine to the in situ synthesized Knoevenagel condensation product (from CH‐acid compounds, such as di‐ and monocarbonyl compounds, dinitrile malonic acid) occurs, leading to spiro‐linked or conventional pyrazoles. Some syntheses of biologically active representatives are shown.

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Diffusion mixing with a volatile tertiary amine as a very efficient technique for 1,3-dipolar cycloaddition reactions proceeding via dehydrohalogenation of stable precursors of reactive dipoles

Abstract: Spontaneous diffusion of a volatile reagent vapors into a solution, containing a stable precursor of an unstable reactive intermediate, may be the simplest method for carrying out some organic reactions,...

Cited by 8 publications

References 45 publications

[3+2]-Cycloaddition of Nitrile Imines to Parabanic Acid Derivatives—An Approach to Novel Spiroimidazolidinediones

[3+2]-Cycloaddition of Nitrile Imines to Parabanic Acid Derivatives—An Approach to Novel Spiroimidazolidinediones

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

Advances in the Synthesis of Heterocycles with Two and Three Heteroatoms using Hydrazonoyl Halides

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