Butyl lithium titration and estimation

Titration of butyllithium (nBuLi or secondary Butyl lithium or tert-Butyl lithium)

Butyl lithiums are usually delivered in “sure seal” bottles which allow using them without contamination by oxygen and moisture. However, frequent use of these bottles damages the septa which can result in decomposition of the compound therefore butyllithium (and other stock alkyllithiums) must be titrated regularly. Many methods are available for this purpose; however, some of the most reliable procedures are given below.

1^st Method:  This method employs 1,3-diphenylacetone p-tosylhydrazone (see Shapiro et al. J. Organomet. Chem. 1980, 186 (2), 155-158) as the reactive agent because of its ability to give persistent color upon anion formation.  Cool a solution of  291 mg (0.769 mmol) hydrazone in 8 mL anhydrous THF under Argon to 0 ^oC and slowly add BuLi via a accurate 2mL syringe (1-2 mL of butyl lithium in syringe should be fine).  During tritration (ice bath): curls of deep yellow will surround each drop of added BuLi, and then dissipate.  At the end-point: persistent (deep) yellow color will be observed.  If you add too much of BuLi ypu will observe deep red color (high concentration of dianion).

Strength of Butyl lithium = (mmol of hydrazone / volume of butyl lithium added)

2^nd Method:  This is GILMAN Double Titration (J. Organomet. Chem. 1964, 2, 447 – 454.) method and a very old method.  It is preferred over single titration methods because it not only gives the concentration of the solution but also provides an indication of the quality of the organolithium.  To determine the total content of base, an aliquot (usually 0.50 to 1.5 ml, depending on the expected concentration) of the solution of the organolithium is quenched with 20 ml of water. The resulting solution of LiOH is titrated with a solution of standardised hydrochloric acid using phenolphthalein as the indicator. To determine the residual content of base of the organolithium, an aliquot (preferably the same amount as before) of the organolithium is reacted with 1,2-dibromoethane as follows: 0.20 ml of dry 1,2-dibromoethane (BE CAREFUL: CARCENOGENIC) are dissolved in 3 ml of dry DEE in an inert atmosphere. The organolithium is added dropwise with vigorous stirring. After 5 min of stirring, the solution is diliuted with 20 ml of water and then titrated as described above. 1,2-Dibromethane reacts with organolithiums as follows:

This procedure destroys the organolithium without producing LiOH, so that the difference of the two titrations gives the exact concentration of the organolithium. A typicale example is given below:

I. A 0.50 ml aliquot of a solution of n-BuLi in hexanes was quenched with water, treated with a few drops of a phenolphthalein solution in water/methanol and titrated with standardised hydrochloric acid unitil complete disappereance of the pink color. When titrating highly flammable organometallics such as t-BuLi, step I should be carried out with degassed water under nitrogen.

II. A second 0.50 ml aliquot was quenched with dibromoethane as described above. After 5 min of stirring, the mixture was diluted with water and after addition of the indicator titrated (with vigorous stirring – it is a biphasic system).

c(HCl) = 0.1034 N; V(HCl)I = 7.90 ml; V(HCl)II = 0.25 ml.

V(HCl)eff = V(HCl)I – V(HCl)II = 7.90 ml – 0.25 ml = 7.65 ml

c(n-BuLi) = [V(HCl)eff x c(HCl)] / V(aliquot) = [7.65 ml x 0.1034 mmol ml-1] / 0.50 ml =

1.58 M

Residual base = [0.25 ml / 7.90 ml] x 100 % = 3.2 %. This value is typical for a high quality organolithium. If the content of residual base is higher than ~ 10 % of the total content of base, the quality of the organolithium is poor, which may be detrimental to very sensitive reactions.

3rd Method: Dry THF (10 mL) is added using a syringe, followed by 2-butanol (0.500 mL, measured as accurately as possible using your 1 mL syringe). Allow the solution to cool for 5 minutes. As accurately as possible, draw 5.00 mL of n-butyl lithium in hexanes from the reagent bottle using 10 mL syringe. (Caution: n-butyl lithium is extremely corrosive and can ignite spontaneously in air. Respect it !!!.) Add the butyl lithium to the solution drop wise, noting when the first rust-red color appears and persists (this is your first endpoint). Once you have persistent color, add the remainder of the butyl lithium to the flask. Immediately rinse your syringe twice with hexane and expel the washings into an open beaker in the hood before cleaning the syringe out with water and acetone (Otherwise, your needle will choke by the formation of lithium hydroxides and carbonates). Next, back titrate the butyl lithium in the flask with 2-butanol until the rust red color is just extinguished (this is your second endpoint). This should be done immediately as the indicator is not stable and will degrade over time. 

Calculate the concentration of the butyllithium solution from both the forward and back titrations and compare these values to the stated value on the bottle. Assume that one mole of butyllithium reacts with one mole of 2-butanol to form the corresponding lithium alkoxide. For tert-BuLi and sec-BuLi you may want to use ether as a solvent and have it ice cooled because these react with THF at room temperature quite fast.