Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 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 Aksenov  1 , Alexander V Aksenov  1 , Lidiya A Prityko  1 , Dmitrii A Aksenov  1 , Daria S Aksenova  1 , Mezvah A Nobi  2 , Michael Rubin  1   2
Affiliations

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

Nicolai A Aksenov et al. ACS Omega. .

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.

PubMed Disclaimer

Conflict of interest statement

The authors declare no competing financial interest.

Figures

Scheme 1
Scheme 1. 2-(3-Oxoindolin-2-ylidene)acetonitriles 1 as Precursors in the Preparation of Antimycobacterial Drugs
Scheme 2
Scheme 2. Synthesis of 2-(3-Oxoindolin-2-ylidene)acetonitriles 1 via the Reductive Cyclization of Nitrochanchones 3
Scheme 3
Scheme 3. Featured Method for the Preparation of 2-(3-Oxoindolin-2-ylidene)acetonitriles 1
Scheme 4
Scheme 4. Retrosynthetic Analysis of the Featured Method
Scheme 5
Scheme 5. Direct Synthesis of 2-(3-Oxoindolin-2-ylidene)acetonitrile 1aa from ortho-Aminochalcone 9aa
Scheme 6
Scheme 6. Preparation of 2-(3-Oxoindolin-2-ylidene)acetonitriles 1 from 4-(2-Aminophenyl)-4-oxo-2-phenylbutanenitriles 6
Scheme 7
Scheme 7. Reactivity of 4-(2-Aminophenyl)-4-oxo-2-phenylbutanenitriles 8 with Protected Aniline Moiety
Scheme 8
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
Scheme 9. Mechanistic Rationale for the Formation of Products 1
Scheme 10
Scheme 10. Mechanistic Rationale for the Formation of Products 11
Scheme 11
Scheme 11. One-Pot Synthesis of Antimycobacterial Pyridazino[4,3-b]indoles 2
See this image and copyright information in PMC

References

    1. Cooksey C. J. Tyrian purple: 6,6′-dibromoindigo and related compounds. Molecules 2001, 6, 736–739. 10.3390/60900736. - DOI
    1. Hoessel R.; Leclerc S.; Endicott J. A.; Nobel M. E.; Lawrie A.; Tunnah P.; Leost M.; Damiens E.; Marie D.; Marko D.; Niederberger E.; Tang W.; Eisenbrand G.; Meijer L. Indirubin, the active constituent of a Chinese antileukaemia medicine, inhibits cyclin-dependent kinases. Nat. Cell Biol. 1999, 1, 60–67. 10.1038/9035. - DOI - PubMed
    1. Leclerc S.; Garnier M.; Hoessel R.; Marko D.; Bibb J. A.; Snyder G. L.; Greengard P.; Biernat J.; Wu Y.-Z.; Mandelkow E.-M.; Eisenbrand G.; Meijer L. Indirubins inhibit glycogen synthase kinase-3β and CDK5/P25, two protein kinases involved in abnormal tau phosphorylation in Alzheimer’s disease. A property common to most cyclin-dependent kinase inhibitors?. J. Biol. Chem. 2001, 276, 251–260. 10.1074/jbc.M002466200. - DOI - PubMed
    1. Meijer L.; Skaltsounis A.-L.; Magiatis P.; Polychronopoulos P.; Knockaert M.; Leost M.; Ryan X. P.; Vonica C. A.; Brivanlou A.; Dajani R.; Crovace C.; Tarricone C.; Musacchio A.; Roe S. M.; Pearl L.; Greengard P. GSK-3-Selective Inhibitors Derived from Tyrian Purple Indirubins. Chem. Biol. 2003, 10, 1255–1266. 10.1016/j.chembiol.2003.11.010. - DOI - PubMed
    1. Polychronopoulos P.; Magiatis P.; Skaltsounis A.-L.; Myrianthopoulos V.; Mikros E.; Tarricone A.; Musacchio A.; Roe S. M.; Pearl L.; Leost M.; Greengard P.; Meijer L. Structural Basis for the Synthesis of Indirubins as Potent and Selective Inhibitors of Glycogen Synthase Kinase-3 and Cyclin-Dependent Kinases. J. Med. Chem. 2004, 47, 935–946. 10.1021/jm031016d. - DOI - PubMed

LinkOut - more resources