Home / Publications / The strategy of combined application of nucleophilic aromatic substitution of hydrogen (SNH ) and transition metal-catalyzed cross-coupling reactions

The strategy of combined application of nucleophilic aromatic substitution of hydrogen (SNH ) and transition metal-catalyzed cross-coupling reactions

Egor Vladimirovich Verbitskiy 1, 2
Egor Vladimirovich Verbitskiy
, 
Valery Nikolaevich Charushin 1, 2
Valery Nikolaevich Charushin
10.71267/mencom.7752
Published 2025-07-17
Focus article , Volume 35, Issue 5, 493-502
2
Share
Cite this
GOST
 | 
Cite this
GOST Copy
Verbitskiy E. V., Charushin V. N. The strategy of combined application of nucleophilic aromatic substitution of hydrogen (SNH ) and transition metal-catalyzed cross-coupling reactions // Mendeleev Communications. 2025. Vol. 35. No. 5. pp. 493-502.
GOST all authors (up to 50) Copy
Verbitskiy E. V., Charushin V. N. The strategy of combined application of nucleophilic aromatic substitution of hydrogen (SNH ) and transition metal-catalyzed cross-coupling reactions // Mendeleev Communications. 2025. Vol. 35. No. 5. pp. 493-502.
RIS
 | 
Cite this
RIS Copy
TY - JOUR
DO - 10.71267/mencom.7752
UR - https://mendcomm.colab.ws/publications/10.71267/mencom.7752
TI - The strategy of combined application of nucleophilic aromatic substitution of hydrogen (SNH ) and transition metal-catalyzed cross-coupling reactions
T2 - Mendeleev Communications
AU - Verbitskiy, Egor Vladimirovich
AU - Charushin, Valery Nikolaevich
PY - 2025
DA - 2025/07/17
PB - Mendeleev Communications
SP - 493-502
IS - 5
VL - 35
ER -
BibTex
 | 
Cite this
BibTex (up to 50 authors) Copy
@article{2025_Verbitskiy,
author = {Egor Vladimirovich Verbitskiy and Valery Nikolaevich Charushin},
title = {The strategy of combined application of nucleophilic aromatic substitution of hydrogen (SNH ) and transition metal-catalyzed cross-coupling reactions},
journal = {Mendeleev Communications},
year = {2025},
volume = {35},
publisher = {Mendeleev Communications},
month = {Jul},
url = {https://mendcomm.colab.ws/publications/10.71267/mencom.7752},
number = {5},
pages = {493--502},
doi = {10.71267/mencom.7752}
}
MLA
Cite this
MLA Copy
Verbitskiy, Egor Vladimirovich, and Valery Nikolaevich Charushin. “The strategy of combined application of nucleophilic aromatic substitution of hydrogen (SNH ) and transition metal-catalyzed cross-coupling reactions.” Mendeleev Communications, vol. 35, no. 5, Jul. 2025, pp. 493-502. https://mendcomm.colab.ws/publications/10.71267/mencom.7752.
Views / Downloads
28 / 17

Keywords

Buchwald–Hartwig reaction
C–H functionalization
cross-coupling
fused aza-aromatic compounds
Heck reaction
pyrazines
pyrimidines
SNH reactions
Sonogashira reaction
Suzuki–Miyaura reaction
triazines

Abstract

Two powerful tools of organic synthesis, transition metal-catalyzed cross-coupling reactions and metal-free SNH reactions leading to nucleophilic displacement of hydrogen of the C(sp2)–H bond, have been combined into one convenient synthetic strategy. This idea has made it possible to obtain a wide variety of substituted azine derivatives, including push–pull systems, new biologically active compounds, organic semiconductors and sensor materials.

Funders

Ministry of Education and Science of the Russian Federation
no. 124020200072-0

References

1.
Heck reaction as a sharpening stone of palladium catalysis
Beletskaya I.P., Cheprakov A.V.
Chemical Reviews, 2000
3.
Palladium-Catalyzed Cross-Coupling: A Historical Contextual Perspective to the 2010 Nobel Prize
Johansson Seechurn C.C., Kitching M.O., Colacot T.J., Snieckus V.
Angewandte Chemie - International Edition, 2012
6.
Ligand-free Heck reactions using low Pd-loading
Reetz M.T., de Vries J.G.
Chemical Communications, 2004
10.
New V-shaped 2,4-di(hetero)arylpyrimidine push-pull systems: Synthesis, solvatochromism and sensitivity towards nitroaromatic compounds
Verbitskiy E.V., Dinastiya E.M., Baranova A.A., Khokhlov K.O., Chuvashov R.D., Yakovleva Y.A., Makarova N.I., Vetrova E.V., Metelitsa A.V., Slepukhin P.A., Rusinov G.L., Chupakhin O.N., Charushin V.N.
Dyes and Pigments, 2018
11.
Synthesis, spectral and electrochemical properties of pyrimidine-containing dyes as photosensitizers for dye-sensitized solar cells
Verbitskiy E.V., Cheprakova E.M., Subbotina J.O., Schepochkin A.V., Slepukhin P.A., Rusinov G.L., Charushin V.N., Chupakhin O.N., Makarova N.I., Metelitsa A.V., Minkin V.I.
Dyes and Pigments, 2014
12.
Nucleophilic Substitution of Hydrogen in Aromatic Systems
Chupakhin O.N., Postovskii I.Y.
Russian Chemical Reviews, 1976
13.
Charushin V.N., Chupakhin O.N.
Mendeleev Communications, 2007
14.
Direct nucleophilic functionalization of C(sp2)–H-bonds in arenes and hetarenes by electrochemical methods
Shchepochkin A.V., Chupakhin O.N., Charushin V.N., Petrosyan V.A.
Russian Chemical Reviews, 2013
16.
CH Functionalization: Collaborative Methods to Redefine Chemical Logic
Davies H.M., Morton D.
Angewandte Chemie - International Edition, 2014
17.
Nucleophilic C–H functionalization of arenes: a new logic of organic synthesis
Chupakhin O.N., Charushin V.N.
Pure and Applied Chemistry, 2017
21.
Pyrimidine-Core Extended π-Systems:  General Synthesis and Interesting Fluorescent Properties
Itami K., Yamazaki D., Yoshida J.
Journal of the American Chemical Society, 2004
22.
Synthesis, photophysical and redox properties of the D-π-A type pyrimidine dyes bearing the 9-phenyl-9H-carbazole moiety
Verbitskiy E.V., Schepochkin A.V., Makarova N.I., Dorogan I.V., Metelitsa A.V., Minkin V.I., Kozyukhin S.A., Emets V.V., Grindberg V.A., Chupakhin O.N., Rusinov G.L., Charushin V.N.
Journal of Fluorescence, 2015
23.
Synthesis and antituberculosis activity of novel 5-styryl-4-(hetero)aryl-pyrimidines via combination of the Pd-catalyzed Suzuki cross-coupling and SNH reactions
Kravchenko M.A., Verbitskiy E.V., Medvinskiy I.D., Rusinov G.L., Charushin V.N.
Bioorganic and Medicinal Chemistry Letters, 2014
24.
Combination of the Suzuki–Miyaura cross-coupling and nucleophilic aromatic substitution of hydrogen (SNH) reactions as a versatile route to pyrimidines bearing thiophene fragments
Verbitskiy E.V., Cheprakova E.M., Slepukhin P.A., Kodess M.I., Ezhikova M.A., Pervova M.G., Rusinov G.L., Chupakhin O.N., Charushin V.N.
Tetrahedron, 2012
26.
C–H Functionalization of Azines
Murakami K., Yamada S., Kaneda T., Itami K.
Chemical Reviews, 2017
30.
Nickel and Palladium Catalysis: Stronger Demand than Ever
Chernyshev V.M., Ananikov V.P.
ACS Catalysis, 2022
31.
Nucleophilic substitution of hydrogen in azines
Chupakhin O.N., Charushin V.N., van der Plas H.C.
Tetrahedron, 1988
32.
New Approach to Biologically Active Indolo[2,3-b]quinoxaline Derivatives through Intramolecular Oxidative Cyclodehydrogenation
Sadykhov G.A., Belyaev D.V., Vakhrusheva D.V., Eremeeva N.I., Khramtsova E.E., Pervova M.G., Rusinov G.L., Verbitskiy E.V., Chupakhin O.N., Charushin V.N.
ChemistrySelect, 2022
33.
Dibenzo[f,h]furazano[3,4-b]quinoxalines: Synthesis by Intramolecular Cyclization through Direct Transition Metal-Free C–H Functionalization and Electrochemical, Photophysical, and Charge Mobility Characterization
Kvashnin Y.A., Verbitskiy E.V., Eltsov O.S., Slepukhin P.A., Tameev A.R., Nekrasova N.V., Rusinov G.L., Nunzi J., Chupakhin O.N., Charushin V.N.
ACS Omega, 2020
34.
New approach to unsymmetrical 1,3-diazatriphenylenes through intramolecular oxidative cyclodehydrogenation
Verbitskiy E.V., Eltsov O.S., Zhilina E.F., Pakhomov I.M., Rusinov G.L., Chupakhin O.N., Charushin V.N.
Tetrahedron, 2019
35.
Synthesis of dithienoquinazolines from pyrimidines via intramolecular nucleophilic aromatic substitution of hydrogen
Verbitskiy E.V., Dinastiya E.M., Baranova A.A., Eltsov O.S., Rusinov G.L., Chupakhin O.N., Charushin V.N.
Chemistry of Heterocyclic Compounds, 2017
36.
Verbitskiy E.V., Baskakova S.A., Belyaev D.V., Vakhrusheva D.V., Eremeeva N.I., Rusinov G.L., Charushin V.N.
Mendeleev Communications, 2021
37.
Synthesis and evaluation of antitubercular activity of fluorinated 5-aryl-4-(hetero)aryl substituted pyrimidines
Verbitskiy E.V., Baskakova S.A., Kravchenko M.A., Skornyakov S.N., Rusinov G.L., Chupakhin O.N., Charushin V.N.
Bioorganic and Medicinal Chemistry, 2016
38.
Synthesis, and structure–activity relationship for C(4) and/or C(5) thienyl substituted pyrimidines, as a new family of antimycobacterial compounds
Verbitskiy E.V., Cheprakova E.M., Slepukhin P.A., Kravchenko M.A., Skornyakov S.N., Rusinov G.L., Chupakhin O.N., Charushin V.N.
European Journal of Medicinal Chemistry, 2015
41.
Nucleophilic Substitution of Hydrogen in Heterocyclic Chemistry
Ma̧kosza M., Wojciechowski K.
Chemical Reviews, 2004
42.
Synthesis of 5-(het)aryl- and 4,5-di(het)aryl-2-(thio)morpholinopyrimidines from 2-chloropyrimidine via SN H and cross-coupling reactions
Cheprakova E.M., Verbitskiy E.V., Ezhikova M.A., Kodess M.I., Pervova M.G., Slepukhin P.A., Toporova M.S., Kravchenko M.A., Medvinskiy I.D., Rusinov G.L., Charushin V.N.
Russian Chemical Bulletin, 2014
44.
In vivo phenotypic drug discovery: applying a behavioral assay to the discovery and optimization of novel antipsychotic agents
Shao L., Campbell U.C., Fang Q.K., Powell N.A., Campbell J.E., Jones P.G., Hanania T., Alexandrov V., Morganstern I., Sabath E., Zhong H.M., Large T.H., Spear K.L.
MedChemComm, 2016
46.
Linear and V-shaped push–pull systems on a base of pyrimidine scaffold with a pyrene-donative fragment for detection of nitroaromatic compounds
Verbitskiy E.V., Baranova A.A., Lugovik K.I., Khokhlov K.O., Chuvashov R.D., Dinastiya E.M., Rusinov G.L., Chupakhin O.N., Charushin V.N.
Journal of the Iranian Chemical Society, 2017
47.
Detection of nitroaromatic explosives by new D–π–A sensing fluorophores on the basis of the pyrimidine scaffold
Verbitskiy E.V., Baranova A.A., Lugovik K.I., Shafikov M.Z., Khokhlov K.O., Cheprakova E.M., Rusinov G.L., Chupakhin O.N., Charushin V.N.
Analytical and Bioanalytical Chemistry, 2016
48.
Microwave-assisted synthesis of 4-(2,2'-bithiophen-5-yl)-5-phenylpyrimidine derivatives as sensors for detection of nitroaromatic explosives
Verbitskiy E.V., Cheprakova E.M., Baranova A.A., Khokhlov K.O., Lugovik K.I., Rusinov G.L., Chupakhin O.N., Charushin V.N.
Chemistry of Heterocyclic Compounds, 2016
50.
The portable detector of nitro-explosives in vapor phase with new sensing elements on a base of pyrimidine scaffold
Baranova A.A., Khokhlov K.O., Chuvashov R.D., Verbitskiy E.V., Cheprakova E.M., Rusinov G.L., Charushin V.N.
Journal of Physics: Conference Series, 2017
51.
New 4,5-di(hetero)arylpyrimidines as sensing elements for detection of nitroaromatic explosives in vapor phase
Verbitskiy E.V., Baranova A.A., Lugovik K.I., Khokhlov K.O., Cheprakova E.M., Shafikov M.Z., Rusinov G.L., Chupakhin O.N., Charushin V.N.
Dyes and Pigments, 2017
52.
Verbitskiy E.V., Baranova A.A., Yakovleva Y.A., Chuvashov R.D., Khokhlov K.O., Dinastiya E.M., Rusinov G.L., Chupakhin O.N., Charushin V.N.
Arkivoc, 2017
53.
Verbitskiy E.V., Baranova A.A., Lugovik K.I., Khokhlov K.O., Cheprakova E.M., Rusinov G.L., Chupakhin O.N., Charushin V.N.
Arkivoc, 2016
54.
New 2 H -[1,2,3]triazolo[4,5- e ][1,2,4]triazolo[1,5- a ]pyrimidine derivatives as luminescent fluorophores for detection of nitroaromatic explosives
Verbitskiy E.V., Gorbunov E.B., Baranova A.A., Lugovik K.I., Khokhlov K.O., Cheprakova E.M., Kim G.A., Rusinov G.L., Chupakhin O.N., Charushin V.N.
Tetrahedron, 2016
55.
Dithienoquinazolines - A Convenient Synthesis by the Oxidative Photocyclization of 4,5-Dithienyl-Substituted Pyrimidines and Their Photophysical Properties
Verbitskiy E.V., Slepukhin P.A., Valova M.S., Cheprakova E.M., Schepochkin A.V., Rusinov G.L., Charushin V.N.
European Journal of Organic Chemistry, 2014
56.
Consecutive SNHand Suzuki-Miyaura Cross-Coupling Reactions - an Efficient Synthetic Strategy to Pyrimidines Bearing Pyrrole and Indole Fragments
Verbitskiy E.V., Rusinov G.L., Charushin V.N., Chupakhin O.N., Cheprakova E.M., Slepukhin P.A., Pervova M.G., Ezhikova M.A., Kodess M.I.
European Journal of Organic Chemistry, 2012
57.
SNH methodology and new approaches to condensed heterocyclic systems
Charushin V.N., Chupakhin O.N.
Pure and Applied Chemistry, 2004
58.
Combination of a Chaperone Synthesis Inducer and an Inhibitor of GAPDH Aggregation for Rehabilitation after Traumatic Brain Injury: A Pilot Study
Dutysheva E.A., Mikhaylova E.R., Trestsova M.A., Andreev A.I., Apushkin D.Y., Utepova I.A., Serebrennikova P.O., Akhremenko E.A., Aksenov N.D., Bon’ E.I., Zimatkin S.M., Chupakhin O.N., Margulis B.A., Guzhova I.V., Lazarev V.F., et. al.
Pharmaceutics, 2022
59.
Reactivity of Naphthyridines toward Nitrogen Nucleophiles
Van Der Plas H.C., Woźniak M., Van Den Haak H.J.
Advances in Heterocyclic Chemistry, 1983
60.
Modern methods for the synthesis of indolo[2,3-b]quinoxalines (microreview)
Sadykhov G.A., Verbitskiy E.V.
Chemistry of Heterocyclic Compounds, 2022
62.
Verbitskiy E.V., Baskakova S.A., Gerasimova N.A., Evstigneeva N.P., Zil’berberg N.V., Kungurov N.V., Kravchenko M.A., Rusinov G.L., Chupakhina O.N., Charushin V.N.
Mendeleev Communications, 2018
66.
Synthesis and approbation of new neuroprotective chemicals of pyrrolyl- and indolylazine classes in a cell model of Alzheimer's disease
Dutysheva E.A., Utepova I.A., Trestsova M.A., Anisimov A.S., Charushin V.N., Chupakhin O.N., Margulis B.A., Guzhova I.V., Lazarev V.F.
European Journal of Medicinal Chemistry, 2021
69.
Recent Advances in Direct C–H Functionalization of Pyrimidines
Verbitskiy E., Rusinov G., Chupakhin O., Charushin V.
Synthesis, 2018
70.
The S HN-Amination of Heteroaromatic Compounds
Gulevskaya A.V., Pozharskii A.F.
Topics in Heterocyclic Chemistry, 2013
71.
Nucleophilic Substitution of Hydrogen in Arenes and Heteroarenes
Mąkosza M., Wojciechowski K.
Topics in Heterocyclic Chemistry, 2013
72.
A Historic Overview of the Metal-Catalyzed Cross-Coupling Reactions
Nishihara Y.
Overlap Determinant Method in the Theory of Pericyclic Reactions, 2012
74.
Rapid and sensitive determination of nitrobenzene in solutions and commercial honey samples using a screen-printed electrode modified by 1,3-/1,4-diazines
Svalova T.S., Saigushkina A.A., Verbitskiy E.V., Chistyakov K.A., Varaksin M.V., Rusinov G.L., Charushin V.N., Kozitsina A.N.
Food Chemistry, 2022
75.
Enhancing the temporal stability of DSSCs with novel vinylpyrimidine anchoring and accepting group
Duerto I., Sarasa S., Barrios D., Orduna J., Villacampa B., Blesa M.
Dyes and Pigments, 2022
76.
Nucleophilic Aromatic Substitution of Hydrogen as a Tool for Heterocyclic Ring Annulation
Gulevskaya A.V., Pozharskii A.F.
Advances in Heterocyclic Chemistry, 2007
77.
Application of electrochemical oxidative methods in the C(sp2) H functionalization of heterocyclic compounds
Chupakhin O.N., Shchepochkin A.V., Charushin V.N.
Advances in Heterocyclic Chemistry, 2020
78.
Investigation of cationic transformations involving 5-ethynyl-4-arylpyrimidines
Shcherbakov S.V., Magometov A.Y., Vendin M.V., Shcherbakova V.Y., Aksenov N.A., Aksenov A.V., Naji O., Rubin M.
Tetrahedron, 2022
80.
Oxidative Amino-Dehydrogenation of Azines
van der Plas H.
Advances in Heterocyclic Chemistry, 2004
83.
C–H Functionalization of Heteroaromatic N-Oxides
Kondo Y.
Topics in Heterocyclic Chemistry, 2013
85.
The first application of push-pull systems based on 1,2,5-oxadiazolo[3,4-b]pyrazine in organic light-emitting diodes and perovskite solar cells
Steparuk A.S., Kvashnin Y.A., Rusinov G.L., Verbitskiy E.V., Aleksandrov A.E., Lypenko D.A., Tameev A.R., Charushin V.N.
Russian Chemical Bulletin, 2023
86.
XIE L., HUANG W., CHEN Y., LAI W.
Chinese Science Bulletin (Chinese Version), 2011
87.
Synthesis of new polycyclic systems based on [1,2,5]chalcogenodiazolo[3,4-b]thieno[3,2-h]quinoxalines
Kvashnin Y.A., Krynina E.M., Medvedeva M.V., Svalova T.S., Kozitsina A.N., Eltsov O.S., Rusinov G.L., Verbitskiy E.V., Charushin V.N.
Russian Chemical Bulletin, 2023
88.
Novel Substituted Azoloazines with Anticoagulant Activity
Spasov A.A., Fedorova O.V., Rasputin N.A., Ovchinnikova I.G., Ishmetova R.I., Ignatenko N.K., Gorbunov E.B., Sadykhov G.A., Kucheryavenko A.F., Gaidukova K.A., Sirotenko V.S., Rusinov G.L., Verbitskiy E.V., Charushin V.N.
International Journal of Molecular Sciences, 2023
89.
Recent Advances in Mn, Fe, Co, Ni-Catalyzed Organic Reactions
Li L., He Y., Yang Y., Guo J., Lu Z., Wang C., Zhu S., Zhu S.
CCS Chemistry, 2024
90.
Kvashnin Y.A., Belyaev D.V., Kodess M.I., Ezhikova M.A., Rusinov G.L., Verbitskiy E.V., Charushin V.N.
Mendeleev Communications, 2023
91.
The green chemistry paradigm in modern organic synthesis
Zlotin Sergei G., Egorova Ksenia S., Ananikov Valentine P., Akulov Alexey A., Varaksin Mikhail V., Chupakhin Oleg N., Charushin Valery N., Bryliakov Konstantin P., Averin Alexey D., Beletskaya Irina P., Dolengovski Egor L., Budnikova Yulia H., Sinyashin Oleg G., Gafurov Zufar N., Kantyukov Artyom O., et. al.
Russian Chemical Reviews, 2024
92.
Metal free C(sp2)[sbnd]H functionalization of nitrogen heterocycles
Charushin V.N., Varaksin M.V., Verbitskiy E.V., Chupakhin O.N.
Advances in Heterocyclic Chemistry, 2024
93.
The chemistry of heterocycles in the 21st century
Charushin Valery N., Verbitskiy Egor V., Chupakhin Oleg N., Vorobyeva Daria V., Gribanov Pavel S., Osipov Sergey N., Ivanov Andrey V., Martynovskaya Svetlana V., Sagitova Elena F., Dyachenko Vladimir D., Dyachenko Ivan V., Krivokolysko Sergey G., Dotsenko Viktor V., Aksenov Aleksandr V., Aksenov Dmitrii A., et. al.
Russian Chemical Reviews, 2024
94.
4-Alkyl-4H-thieno[2′,3′:4,5]pyrrolo[2,3-b]quinoxaline Derivatives as New Heterocyclic Analogues of Indolo[2,3-b]quinoxalines: Synthesis and Antitubercular Activity
Sadykhov G.A., Belyaev D.V., Khramtsova E.E., Vakhrusheva D.V., Krasnoborova S.Y., Dianov D.V., Pervova M.G., Rusinov G.L., Verbitskiy E.V., Charushin V.N.
International Journal of Molecular Sciences, 2025