. 2022 Apr 15;7(16):14345-14356.

doi: 10.1021/acsomega.2c01238. eCollection 2022 Apr 26.

Oxidative Cyclization of 4-(2-Aminophenyl)-4-oxo-2-phenylbutanenitriles into 2-(3-Oxoindolin-2-ylidene)acetonitriles

Nicolai A Aksenov¹, Alexander V Aksenov¹, Lidiya A Prityko¹, Dmitrii A Aksenov¹, Daria S Aksenova¹, Mezvah A Nobi², Michael Rubin^{1

2}

Affiliations

¹ Department of Chemistry, North Caucasus Federal University, 1a Pushkin St., Stavropol 355017, Russian Federation.
² Department of Chemistry, University of Kansas, 1567 Irving Hill Road, Lawrence, Kansas 66045, United States.

PMID: 35573208
PMCID: PMC9089741
DOI: 10.1021/acsomega.2c01238

Oxidative Cyclization of 4-(2-Aminophenyl)-4-oxo-2-phenylbutanenitriles into 2-(3-Oxoindolin-2-ylidene)acetonitriles

Nicolai A Aksenov et al. ACS Omega. 2022.

. 2022 Apr 15;7(16):14345-14356.

doi: 10.1021/acsomega.2c01238. eCollection 2022 Apr 26.

Authors

Nicolai A Aksenov¹, Alexander V Aksenov¹, Lidiya A Prityko¹, Dmitrii A Aksenov¹, Daria S Aksenova¹, Mezvah A Nobi², Michael Rubin^{1

2}

Affiliations

¹ Department of Chemistry, North Caucasus Federal University, 1a Pushkin St., Stavropol 355017, Russian Federation.
² Department of Chemistry, University of Kansas, 1567 Irving Hill Road, Lawrence, Kansas 66045, United States.

PMID: 35573208
PMCID: PMC9089741
DOI: 10.1021/acsomega.2c01238

Abstract

A facile and highly efficient method for the preparation of 2-(3-oxoindolin-2-ylidene)acetonitriles from 4-(2-aminophenyl)-4-oxo-2-phenylbutanenitriles is described. The featured transformation operates via nucleophilic intramolecular cyclization and involves oxidation of the aniline moiety. Overall, this modification allowed for the improvement of yields and expansion of the reaction scope.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

**Scheme 1. 2-(3-Oxoindolin-2-ylidene)acetonitriles 1 as Precursors in the Preparation of Antimycobacterial Drugs**

**Scheme 2. Synthesis of 2-(3-Oxoindolin-2-ylidene)acetonitriles 1 via the Reductive Cyclization of Nitrochanchones 3**

**Scheme 3. Featured Method for the Preparation of 2-(3-Oxoindolin-2-ylidene)acetonitriles 1**

**Scheme 4. Retrosynthetic Analysis of the Featured Method**

Scheme 5. Direct Synthesis of 2-(3-Oxoindolin-2-ylidene)acetonitrile **1aa** from *ortho*-Aminochalcone **9aa**

**Scheme 6. Preparation of 2-(3-Oxoindolin-2-ylidene)acetonitriles 1 from 4-(2-Aminophenyl)-4-oxo-2-phenylbutanenitriles 6**

**Scheme 7. Reactivity of 4-(2-Aminophenyl)-4-oxo-2-phenylbutanenitriles 8 with Protected Aniline Moiety**

**Scheme 8. One-Pot Approach for the Preparation of N-Alkylated 2-(3-oxoindolin-2-ylidene)acetonitriles 7 from 4-(2-Aminophenyl)-4-oxo-2-phenylbutanenitriles 6**

**Scheme 9. Mechanistic Rationale for the Formation of Products 1**

**Scheme 10. Mechanistic Rationale for the Formation of Products 11**

**Scheme 11. One-Pot Synthesis of Antimycobacterial Pyridazino[4,3-b]indoles 2**

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Oxidative Cyclization of 4-(2-Aminophenyl)-4-oxo-2-phenylbutanenitriles into 2-(3-Oxoindolin-2-ylidene)acetonitriles

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Oxidative Cyclization of 4-(2-Aminophenyl)-4-oxo-2-phenylbutanenitriles into 2-(3-Oxoindolin-2-ylidene)acetonitriles

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Abstract

Conflict of interest statement

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