Organometallic Synthesis of 2,3,6,7-Tetrasubstituted 1,8-Bis(dimethylamino)naphthalenes for Investigation of the Double Buttressing Effect in Proton Sponges

Abstract

The lithiation of 2,7-disubstituted derivatives of 1,8bis(dimethylamino)naphthalene (DMAN, proton sponge) bearing potentially ortho-directing OMe, NMe 2 , and SMe groups was studied. It has been shown that OMe groups facilitate selective dual βlithiation of the naphthalene moiety while the 2(7)-NMe 2 groups allow only monolithiation presumably due to the decreased acidity of the ring C−H bonds and conformational immobilization after coordination to the lithium atom. In contrast, the SMe groups provided no ring lithiation and underwent deprotonation of their methyl fragment. The first representatives of previously unknown 2,3,6,7-tetrasubstituted DMANs have been synthesized in good yield after treatment of 2,7-dimethoxy-3,6-dilithio DMAN with the appropriate electrophiles (MeI, Me 2 S 2 , Me 3 SiCl, DMF, etc.). Because the exceedingly high basicity of 2,7-dimethoxy DMAN is commonly attributed to the so-called "buttressing effect" (BE), the availability of 2,3,6,7-tetrasubstituted species provided the first opportunity to study the double BE version. Using X-ray diffraction and basicity measurements, we showed that due to the high conformational mobility of the methoxy groups, the most striking manifestations of double BE are the strong planarization of peri-NMe 2 groups and a significant decrease in basicity, while the length and the other properties of the intramolecular NHN hydrogen bond in the corresponding protonated species undergo minor changes.

“Buttressing Effect” in the Halogen‐Lithium Exchange in ortho‐Bromo‐N,N‐dimethylanilines and Related Naphthalenes

“…On the contrary, usage of diethyl ether and especially tetrahydrofuran gives poorly reproducible results and an incomplete conversion (lines 6,7). We attribute this result to the relative ease of metalation of the SMe group in such solvents, as it was recently demonstrated [33] …”

“…We attribute this result to the relative ease of metalation of the SMe group in such solvents, as it was recently demonstrated. [33] Treatment of aniline 4 d, which contains a conformationally rigid methyl substituent, with n-BuLi leads to a much more difficult halogen-metal exchange in comparison with 4 c. Thus, at À 25 °C, only trace amounts of 6 d are observed in hexane and in diethyl ether (runs 8,9). Switching to tetrahydrofuran allows to achieve significant conversion already after 2 minutes (run 10).…”