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
. 2023 Oct 30;28(21):7335.
doi: 10.3390/molecules28217335.

An Unusual Rearrangement of Pyrazole Nitrene and Coarctate Ring-Opening/Recyclization Cascade: Formal CH-Acetoxylation and Azide/Amine Conversion without External Oxidants and Reductants

Elena Chugunova  1 , Almir S Gazizov  1 , Daut Islamov  1 , Victoria Matveeva  1 , Alexander Burilov  1 , Nurgali Akylbekov  2 , Alexey Dobrynin  1 , Rakhmetulla Zhapparbergenov  2 , Nurbol Appazov  2   3 , Beauty K Chabuka  4 , Kimberley Christopher  4 , Daria I Tonkoglazova  4 , Igor V Alabugin  1   4
Affiliations

An Unusual Rearrangement of Pyrazole Nitrene and Coarctate Ring-Opening/Recyclization Cascade: Formal CH-Acetoxylation and Azide/Amine Conversion without External Oxidants and Reductants

Elena Chugunova et al. Molecules. .

Abstract

We report an unusual transformation where the transient formation of a nitrene moiety initiates a sequence of steps leading to remote oxidative C-H functionalization (R-CH3 to R-CH2OC(O)R') and the concomitant reduction of the nitrene into an amino group. No external oxidants or reductants are needed for this formal molecular comproportionation. Detected and isolated intermediates and computational analysis suggest that the process occurs with pyrazole ring opening and recyclization.

Keywords: 1H-pyrazole; cyclization; fragmentation; furoxan; nitrene.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Scheme 1
Scheme 1
The original goal of this work: fusion of two dinitrogen heterocycles, pyrazole and furoxan, [49,50,51,52].
Scheme 2
Scheme 2
Reaction of edaravone 1 with POCl3, following nitration and azidation, with formation of 5-azido-3-methyl-4-nitro-1-(4-nitrophenyl)-1H-pyrazole 4 [55].
Scheme 3
Scheme 3
Unexpected redox disproportionation of α-nitroazide 4.
Scheme 4
Scheme 4
Reaction of nitroazide 4 with selected carboxylic acids and butanol.
Figure 1
Figure 1
(A): Fragment of crystal packing of compound 5a, (B): molecular structure of compound 6.
Scheme 5
Scheme 5
Suggested mechanism for the formation of unusual products in the attempted synthesis of pyrazole/furoxan hybrid. Pathways discarded from the computational evidence are shown in the red background. The suggested plausible path is shown in blue. Both cyclization and fragmentation proceed from the singlet state.
Scheme 6
Scheme 6
General coarctate ring-opening reaction induced by an electron-deficient and coordinatively unsaturated atom, e.g., a carbene or a nitrene. The parent carbene/nitrene species can be formed via decomposition of diazo compounds or azides, respectively.
See this image and copyright information in PMC

References

    1. Rostovtsev V.V., Green L.G., Fokin V.V., Sharpless K.B. A stepwise huisgen cycloaddition process: Copper(I)-catalyzed regioselective “ligation” of azides and terminal alkynes. Angew. Chem. Int. Ed. Engl. 2002;41:2596–2599. doi: 10.1002/1521-3773(20020715)41:14<2596::AID-ANIE2596>3.0.CO;2-4. - DOI - PubMed
    1. Pearson T.J., Shimazumi R., Driscoll J.L., Dherange B.D., Park D.-I., Levin M.D. Aromatic nitrogen scanning by ipso-selective nitrene internalization. Science. 2023;381:1474–1479. doi: 10.1126/science.adj5331. - DOI - PMC - PubMed
    1. Boyer J.H. Reduction of Organic Azides to Primary Amines with Lithium Aluminum Hydride. J. Am. Chem. Soc. 1951;73:5865–5866. doi: 10.1021/ja01156a507. - DOI
    1. Rolla F. Sodium borohydride reactions under phase-transfer conditions: Reduction of azides to amines. J. Org. Chem. 1982;47:4327–4329. doi: 10.1021/jo00143a031. - DOI
    1. Ranu B.C., Sarkar A., Chakraborty R. Reduction of Azides with Zinc Borohydride. J. Org. Chem. 1994;59:4114–4116. doi: 10.1021/jo00094a021. - DOI

LinkOut - more resources