Org. Synth. 1984, 62, 101
DOI: 10.15227/orgsyn.062.0101
PREPARATION OF LOW-HALIDE METHYLLITHIUM
[Lithium, methyl-]
Submitted by Michael J. Lusch, William V. Phillips, Ronald F. Sieloff, Glenn S. Nomura, and Herbert O. House
1.
Checked by Gregory S. Bisacchi and Robert V. Stevens.
1. Procedure
Caution! The fine lithium dispersion used in this preparation, once washed to remove the mineral oil coating, will ignite spontaneously if exposed to air. Also, the methyl chloride and ether used are very volatile and highly flammable. The entire preparation, including the disposal of any residual lithium, should be performed in an efficient hood with a safety shield in front of the apparatus. A suitable dry-powder fire extinguisher should be kept at hand to extinguish any fires resulting from the accidental spillage of the washed lithium dispersion or of the methyllithium solution.
A dry, 1-L, three-necked, round-bottomed flask equipped with a large Teflon-covered magnetic stirring bar, a thermometer, and a dry ice condenser (Note 1) is flushed with argon (Note2), then capped with a serum stopper, and subsequently maintained under a positive pressure of argon (Note 2). A 30% dispersion of lithium metal (in mineral oil) containing 1% sodium (13.9 g, 2.00 g-atom of lithium) (Note 3) is rapidly weighed and transferred to the flask.
The
lithium is washed three times by transferring approximately
150-mL portions of anhydrous ethyl ether (Note 4) into the flask through the serum stopper by forced siphon through a
stainless-steel cannula, stirring the resulting suspension of
lithium briefly, allowing the
lithium to rise to the surface, and finally withdrawing the major part of the underlying ether by forced siphon through a cannula. Anhydrous
ethyl ether (500 mL) is added to the resultant oil-free
lithium.
Methyl chloride gas (bp
−24°C,
d−24°C 0.99 g/mL) from a compressed gas cylinder is passed through a flask containing Linde 4A molecular sieves and into a dry,
100-mL Pyrex graduated cylinder equipped with a
24/40 standard taper joint attached to a
Claisen adapter and
dry ice condenser, and cooled to −24°C with a bath of dry ice–
acetone (Figure 1). When
52.7 mL (52.5 g, 1.04 mol) of liquid methyl chloride has been collected, the adapter and condenser are removed, several boiling chips are added to the cold (−24°C) graduated cylinder, and the cylinder is stoppered with a rubber septum through which is inserted a stainless-steel cannula. The other end of this cannula is inserted through the rubber septum of the flask so that its tip is just above the liquid surface of the reaction flask. Dry ice–
acetone is then added to the condenser attached to the reaction flask. Vigorous stirring of the ethereal
lithium dispersion is begun and the
methyl chloride is added over approximately a 1.5-hr period. The rate at which
methyl chlorideis distilled into the reaction vessel is controlled by slight cooling or warming of the graduated cylinder that contains the liquid
methyl chloride. During addition, the initial grey suspension changes to a brown to purple suspension; by the end of the addition, little, if any,
lithium metal should be seen floating on the surface of the ether solution when stirring is interrupted. After the addition of
methyl chloride is complete, the reaction mixture is stirred at 25°C for an additional 0.5–1 hr and then allowed to stand overnight or longer
(Note 5) at 25°C under a static
argon atmosphere, whereupon the precipitated
lithium chloride settles to the bottom of the flask. The dry ice condenser and thermometer are removed from the flask and replaced with rubber septa. The supernatant
methyllithium solution is transferred by forced siphon using a
large-gauge cannula through a glass wool pad
(Note 6) into a receiving flask previously flushed with an inert gas
(Figure 2). The receiving flask, which contains the filtrate, a pale-yellow solution of
methyllithium, is removed
(Note 7) and stored in a refrigerator for 12–24 hr during, which time an additional small quantity of
lithium chloride separates as fine crystals. The resulting supernatant solution is transferred with a stainless-steel cannula and a slight positive pressure of
argon or
nitrogen into one or more suitable
oven-dried, nitrogen-filled storage bottles capped with rubber septa. Two 1-mL aliquots of the solution are removed with a hypodermic syringe for a modified Gilman titration
(Note 8) and a 5-mL aliquot is removed with a hypodermic syringe to determine the halide concentration
(Note 9). The solution contains 1.40–1.77
M methyllithium accompanied by 0.07–0.09
M lithium chloride corresponding to a
70–89% yield of
methyllithium. If this solution is protected from
oxygen and moisture, it may be stored at 0–25°C for several months (and remain active).
Figure 1. Condensing the methyl chloride.
Figure 2. Decanting the methyllithium solution.
2. Notes
1.
The dry ice condenser used with the apparatus should have sufficient condensing capacity to prevent the loss of significant amounts of
methyl chloride; a
condenser 38 cm long and 3.8 cm in diameter was suitable.
Since finely divided lithium floats on the surface of the solvent and will be in contact with the atmosphere in the reaction vessel, an argon atmosphere, rather than a nitrogen atmosphere, should be used to avoid formation of the insoluble reddish-brown lithium nitride.
2.
A slight positive pressure of
argon was maintained in the vessel throughout the reaction by using an
argon line connected to both a
bubbler containing Nujol and the inlet on the
dry ice condenser.
3.
A dispersion in mineral oil of 30% (by weight) of
lithium containing 1% by weight of
sodium is marketed by Alfa Products, Morton Thiokol, Inc. This oilcoated dispersion may be exposed to the air during transfer and weighing and is conveniently transferred from its container by pouring through a
wide-mouth funnel. Small quantities of the dispersion that adhere to the apparatus may be disposed of by rinsing in a stream of warm water to lower the viscosity of the oil and allow the suspended
lithium to react with water at a controlled rate. To dispose of large quantities of this dispersion (or any quantity of
lithium powder no longer coated with oil), the material should be suspended in anhydrous
ether under an
argon atmosphere and
tert-butyl alcohol should be added dropwise to the suspension until all of the
lithium metal has been consumed. Since
hydrogen is liberated during these disposal procedures, they should be performed in an efficient hood.
4.
Anhydrous
ethyl ether was distilled from
lithium aluminum hydride immediately before use.
5.
Although most of the
lithium chloride separates from the ether solution as a finely divided solid during the reaction, additional small quantities of
lithium chloride continue to separate for 12–14 hr. After standing overnight, a typical reaction contains a precipitate of finely divided brownish-pink solid below a clear, pale-yellow solution.
6.
A
convenient filter was constructed by packing glass wool, previously dried in an oven, into a 20-mL Luer-Lok syringe barrel fitted with a 15-gauge needle. The syringe barrel was capped with a serum stopper. A
large-diameter cannula (at least 15 gauge) should be used to transfer the
methyllithium solution from the flask to the filter since smaller-gauge cannulas are frequently plugged by solid particles.
7.
As soon as the receiver containing the
methyllithium solution has been removed and stoppered, the residual solids in the reaction flask and the filtration apparatus should be rinsed into another receiver with anhydrous
ether under an atmosphere of
argon or
nitrogen. The ether slurry of solids, which may contain some unchanged
lithium metal, should be treated cautiously in a hood with
tert-butyl alcohol to consume any residual
lithium metal before the mixture is discarded.
8.
One 1-ml aliquot is added to
1.0 mL of freshly distilled 1,2-dibromoethane (bp
132°C) in an oven-dried flask that contains a static atmosphere of
nitrogen or
argon. After the resulting solution has been allowed to stand at 25°C for 5 min, it is diluted with 10 mL of water and titrated for base content (residual base) to a
phenolphthalein endpoint with standard
0.100 M hydrochloric acid. The second 1-mL aliquot is added cautiously to 10 mL of water and then titrated for base content (total base) to a
phenolphthalein endpoint with standard aqueous 0.100
M hydrochloric acid. The
methyllithium concentration is the difference between the total base and residual base concentrations.
2 3 Alternatively, the
methyllithium concentration may be determined by titration with a standard solution of
sec-butyl alcohol employing
2,2'-bipyridyl as an indicator.
4 59.
To determine the concentration of chloride ion,
6 7 a 5-mL aliquot of the
methyl-lithium solution is cautiously added to 25 mL of water and the resulting solution is acidified with concentrated
sulfuric acid and then treated with
2–3 mL of ferric ammonium sulfate [Fe(NH4) (SO4)2 12 · H2O] indicator solution and
2–3 mL of benzyl alcohol. The resulting mixture is treated with
10.0 mL of standard aqueous 0.100 M silver nitrate solution and then titrated with standard aqueous
0.100 M potassium thiocyanate solution to a brownish-red endpoint.
3. Discussion
Although ethereal solutions of
methyllithium may be prepared by the reaction of
lithium wire with either
methyl iodide8 or
methyl bromide9 in ether solution, the molar equivalent of
lithium iodide or
lithium bromide formed in these reactions remains in solution and forms, in part, a complex with the
methyllithium.
10 Certain of the ethereal solutions of
methyllithium currently marketed by several suppliers including Alfa Products, Morton Thiokol, Inc., Aldrich Chemical Company, and Lithium Corporation of America, Inc., have been prepared from
methyl bromide and contain a full molar equivalent of
lithium bromide. In several applications such as the use of
methyllithium to prepare
lithium dimethylcuprate11 12 or the use of
methyllithium in
1,2-dimethyoxyethane to prepare
lithium enolates from enol acetates or
trimethylsilyl enol ethers,
5 the presence of this lithium salt interferes with the titration and use of
methyllithium. There is also evidence indicating that the stereochemistry observed during addition of
methyllithium to carbonyl compounds may be influenced significantly by the presence of a lithium salt in the reaction solution.
13 For these reasons it is often desirable to use ethereal solutions of
methyllithium that do not contain an equivalent amount of
lithium iodide or
lithium bromide.
The reaction of
lithium with
methyl chloride in
ether solution produces a solution of
methyllithium from which most of the relatively insoluble
lithium chloride precipitates. Ethereal solutions of "halide-free"
methyllithium, containing 2–5 mol % of lithium chloride, were formerly marketed by Foote Mineral Company and by Lithium Corporation of America, Inc., but this product has been discontinued by both companies. Comparable solutions are also marketed by Alfa Products and Aldrich Chemical Company; these solutions have a limited shelf life and older solutions have often deteriorated badly even before the container is opened. Since an ether solution of
methyl chloride reacts very slowly with
lithium wire used in reactions with
methyl bromide or
methyl iodide, the present procedure
14 uses a finely divided suspension of
lithium metal containing 1% (by weight) of
sodium10,15 to achieve a rapid reaction with
methyl chloride. The finely divided
lithium containing 1%
sodium is marketed as a 30% (by weight) dispersion in mineral oil and must be washed free of this protective hydrocarbon diluent before use in order to avoid contamination of the final
methyllithium reagent with a substantial amount of a mixture of high molecular weight hydrocarbons. Since
lithium is less dense than common organic solvents such as
diethyl ether or
pentane, the washing procedure must be done with special care to avoid starting a fire with the pyrophoric, finely divided
lithium.
3 Finely divided
lithium with somewhat higher or lower percentages of
sodium are expected to work equally well.
This preparation is referenced from:
Appendix
Chemical Abstracts Nomenclature (Collective Index Number);
(Registry Number)
H2O
1,2-dimethyoxyethane
trimethylsilyl enol ethers
sulfuric acid (7664-93-9)
hydrochloric acid (7647-01-0)
ether,
ethyl ether,
diethyl ether (60-29-7)
hydrogen (1333-74-0)
silver nitrate (7761-88-8)
oxygen (7782-44-7)
nitrogen (7727-37-9)
methyl chloride (74-87-3)
acetone (67-64-1)
sodium (13966-32-0)
Benzyl alcohol (100-51-6)
1,2-dibromoethane (106-93-4)
methyl bromide (74-83-9)
Methyl iodide (74-88-4)
potassium thiocyanate (333-20-0)
Pentane (109-66-0)
phenolphthalein (77-09-8)
lithium (7439-93-2)
lithium aluminum hydride (16853-85-3)
Methyllithium,
Lithium, methyl-,
methyl-lithium (917-54-4)
Lithium chloride (7447-41-8)
argon (7440-37-1)
tert-butyl alcohol (75-65-0)
lithium iodide (10377-51-2)
sec-butyl alcohol (78-92-2)
2,2'-bipyridyl (366-18-7)
lithium dimethylcuprate
lithium bromide (7550-35-8)
lithium nitride (26134-62-3)
ferric ammonium sulfate
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