Abstract: A systematic study of the direction of nucleophilic attack of the nucleophiles Me3MEMe2 (M = Si, Sn; E = P, As), NaOMe, LiR (R = Me, nBu, Ph) and PhMgBr on 5,6,7,8-tetrafluoroquinoline (1), 6-CF3-5,7,8-trifluoroquinoline (2) and 5,7,8-trifluoroquinoline (3) was performed with the aim to develop synthetic routes to specific functional derivatives and to gain a deeper insight into the mechanisms governing the regioselectivity. With the fairly "soft" nucleophiles Me3MEMe2 in general mixtures of 7-Me2EC(main product) and 6-Me2EC-derivatives (side product) are formed (Schemes 1, 2, 4). Sulfuration of the isomer mixtures with E = P yields mixtures of the corresponding thiophosphano derivatives. The observed regioselectivity is explained by a concerted action of two factors: (i) The influence of the heteroatom N on the stabilization of the a-complex type transition states and (ii) the collective effect of four fluorine substituents favouring 6- and 7-substitution. The reaction of with sodium methoxide (Scheme 3) was carried out to test the early conclusion on the exclusive formation of 7-methoxy-5,6,8-trifluoroquinoline (14) [2], made on the basis of a GC-analysis. For that purpose the molar ratio 1 : MeO- was varied from 1 : 1.25 over 1 : 1 to 1 : 0.5. - In the reactions of the quinoline precursors 1-3 with the organometallic reagents LiR (R = Me, nBu, Ph) and PhMgBr (Scheme 5) products of the nucleophile-addition at position 2 were obtained in high yields, which with hydrochloric acid led to 2-R-1,2-dihydro-5,6,7,8-tetrafluoroquinolines. In contact with air or by reaction with MnO2, oxidation to aromatic 2-R-5,6,7,8-tetrafluoroquinolines occurred. To rationalize the observed differences between the "soft" Me3MEMe2 and the "hard" carbon-centred nucleophiles, two different hypothetic mechanisms are discussed. Since most of the compounds have been obtained in reaction mixtures, the assignment to structural formulae is mainly based on GCMS and CMS analyses together with H-1-, F-19- and P-31 NMR data and comparison with literature information and with spectra registered for individual compounds. In addition, the molecular structures of the representatives 6, 20 and 29, determined by X-ray analyses, prove the structural formulae deduced from the spectra of products.

Cite: Panteleeva E. , Shteingarts V. , Grobe J. , Krebs B. , Triller M. , Rabeneck H.
Regioselectivity of 5,6,7,8-tetrafluoroquinoline and 6-X-trifluoroquinoline (X=CF3,H) in reactions with nucleophiles
Zeitschrift fur Anorganische und Allgemeine Chemie. 2003. V.629. N1. P.71-82. DOI: 10.1002/zaac.200390020 WOS Scopus OpenAlex

Dates:

Published print:

Jan 1, 2003

Identifiers:

Web of science:	WOS:000182160800012
Scopus:	2-s2.0-0037259423
OpenAlex:	W2056684011

Citing:

DB	Citing
Web of science	15
Scopus	15
OpenAlex	13

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