Sciencemadness Discussion Board - lithiation of 8-bromoquinoline

lithiation of 8-bromoquinoline

DNA - 5-8-2009 at 00:55

Does anyone know what possibly could happen here.
Concerning the mechanism.

I haven't done many litation reactions so I don't really know in this case if it will attach twice to the precursor since t-BuLi is present as a dimer usually and then I've read quite some about ortho litations so will it not kick of the bromine but attach next to the bromine?

[Edited on 5-8-2009 by DNA]

donlaszlow - 5-8-2009 at 15:07

It kicks the bromine off. I use lithiation to add formyl groups on phenothiazine rings, and if my goal is in positions 3 and 7, than I use 3,7-dibromo-10-methyl phenothiazine as a precursor.This is called the S. Ebdrup (1998) method. Yields are quite large (70-80%) in comparison to the Vilsmayer-Haak method (20-40%).
So this is bad news for you

I hope you find some method that might help

BTW I used n-BuLi

[Edited on 6-8-2009 by donlaszlow]

Jor - 5-8-2009 at 15:14

I don't think there is a + charge on the lithium

Nicodem - 5-8-2009 at 23:52

No, there surely is no charge on lithium. That is an error. And the nitrogen on the lowest structure would have a formal (+) charge.

Quote:

No, t-BuLi, s-BuLi and n-BuLi all cause Li-Br exchange at -78°C. This is an incredibly fast exchange, approaching the speed of proton transfers even though it is based on single electron transfer mechanisms. The difference when using t-BuLi is in that you use 2 equivalents in order to get a clean reaction mixture (with n-BuLi you end up with n-butyl bromide besides the aryl lithium). The other equivalent is needed to eliminate the bromide from t-BuBr so you end up only with LiBr, isobutane and isobutene as side products, which is important in some reactions where n-BuBr or s-BuBr interfere.
If you want to ortho-lithiate aryl halides you need to use lithium diisopropylamide (LDA) or lithium tetramethylpiperidide (LiTMP). With lithium amides the Li-Br exchange is too much uphill in the thermodynamic sense that it does not occur (C-X vs. N-X bond!), so that the direct lithiation of the neighbouring H is thus made possible. The acidity of ortho-H toward lithium in the aryl halides is F > Cl > Br > I (due to orbital sizes and inductive effect). orho-Lithiated aryl halides are only stable at low temperatures. They often start to decompose to benzynes. Also, it is important to understand that direct peri- and ortho-lithiation is a slow reaction in comparison to Li-X exchange (and with LDA and LiTMP it is also an equilibrium reaction). Unless TMEDA is added, it can take several hours or heating up to -20 °C or even up to 20 °C, but this depends on the directing group. Some directing groups like the R2NCOO- group will allow the lithiation to occur even at -78 °C in matter of minutes (for the conditions required in regard to the directiong group see page 504 in The chemistry of organolithium compounds, Rappoport and Marek, 2004). Also worth checking is Organolithiums: selectivity for synthesis, Clayden, 2002 and Organolithium methods, Wakefield, 1988.