Metalated azolo[1,2,4]triazines. II. Generation, C(4)-substituent dependent stability and electrophile trapping of 7-lithiopyrazolo[5,1-c][1,2,4]triazines

Metalated azolo[1,2,4]triazines. II. Generation, C(4)-substituent dependent stability and electrophile trapping of 7-lithiopyrazolo[5,1-c][1,2,4]triazines Full article

Journal

Journal of Organometallic Chemistry
ISSN: 1872-8561 , E-ISSN: 0022-328X

Output data

Year: 2019, Volume: 896, Pages: 168-182 Pages count : 15 DOI: 10.1016/j.jorganchem.2019.06.009

Authors

Ivanov Sergey M. ¹ , Dmitrienko Artem O. ^2,1 , Medvedev Michael G. ^2,3,1,4 , Mironovich Lyudmila M. ⁵

Affiliations

1	N.D. Zelinsky Institute of Organic Chemistry Russian Academy of Sciences, 119991, Moscow, Leninsky Prospekt, 47, Russia
2	A.N. Nesmeyanov Institute of Organoelement Compounds Russian Academy of Sciences, 119991, Moscow, Vavilova St. 28, Russia
3	National Research University Higher School of Economics (HSE), 101000, Moscow, Myasnitskaya Str. 20, Russia
4	Department of Chemistry, Lomonosov Moscow State University, 119991, Moscow, Leninskie Gory 1/3, Russia
5	Southwest State University, 305040, Kursk, 50 Years of October Street, 94, Russia

7-Lithio-3-tert-butylpyrazolo[5,1-c][1,2,4]triazines have been generated for the first time using one-pot nucleophilic addition and metal-halogen exchange reactions in 7-bromopyrazolo[5,1-c][1,2,4]triazines. It was found that the stability of 7-lithio species depends highly on the substitution pattern at the C(4) ring position. The rate of the pyrazole ring opening reaction roughly followed the order of the electronegativity of substituents: rapid cycle cleavage took place already at −97 °C for C(4) = O, CH–Ar, CH–C≡CPh, while CH–Alk and CH2 substituted derivatives were stable in these conditions (Ar = Ph, 4-tolyl; Alk = t-Bu, n-Bu, n-Pr). Quantum chemical modeling showed that the ring opening is accompanied with simultaneous shift of the Li atom towards N(6). Calculated free activation energies are in range from 12.7 to 15.0 kcal*mol−1. Electrophile trapping of fairly stable 4-alkyl-1,7-metalated derivatives at −97 °C using H2O, DMF or PhCHO allowed the selective side-chain functionalization. Tautomeric exo- and endocyclic double bond equilibrium in the isolated 4-oxo and 4-aryl substituted ring opening products is also discussed on the basis of IR, 1H, 13C NMR, high resolution mass spectra and X-ray powder diffraction analysis.

Ivanov S.M. , Dmitrienko A.O. , Medvedev M.G. , Mironovich L.M.
Metalated azolo[1,2,4]triazines. II. Generation, C(4)-substituent dependent stability and electrophile trapping of 7-lithiopyrazolo[5,1-c][1,2,4]triazines
Journal of Organometallic Chemistry. 2019. V.896. P.168-182. DOI: 10.1016/j.jorganchem.2019.06.009 WOS Scopus OpenAlex

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