Lithiation of 2,4,5,7-Tetrabromo-1,8-bis(dimethylamino)naphthalene: Peculiarities of Directing Groups' Effects and the Possibility of Polymetalation

The bromine-lithium exchange sequence upon interaction of 2,4,5,7-tetrabromo-1,8-bis(dimethylamino)naphthalene with n-BuLi was studied. Experimental results were explained by means of quantum chemical calculations. It was demonstrated that the first exchange occurs in position 4 due to the significant decrease of a steric strain of the molecule. The second exchange takes place in either position 5 or 7 due to the even more negative charge distribution in the naphthalene core. As a result, the third exchange leads to the species containing lithium in positions 2,4,5 or 2,4,7. Using a large excess of n-BuLi in hexane, 2,4,5,7-tetralithio-1,8-bis(dimethylamino)naphthalene was successfully prepared. The latter was used for the synthesis of several tetrasubstituted derivatives of 1,8-bis(dimethylamino)naphthalene by quenching with different electrophiles.

Automated summary

The bromine-lithium exchange sequence of 2,4,5,7-tetrabromo-1,8-bis(dimethylamino)naphthalene with n-BuLi was studied and explained through quantum chemical calculations. The first exchange occurred at position 4 due to steric strain reduction, followed by exchanges at positions 5 or 7 based on charge distribution, resulting in lithium-containing species at positions 2,4,5 or 2,4,7. Additionally, 2,4,5,7-tetralithio-1,8-bis(dimethylamino)naphthalene was successfully prepared for further synthesis of tetrasubstituted derivatives.