Methyllithium, ether solution standardizing

The submitters used an ether solution of halide-free methyl-lithium, purchased from Foote Mineral Company, and the checkers prepared the compound from methyl chloride and lithium metal in ether according to the literature.2 The solution was standardized before use by the titration procedure described in a previous volume of this series.3 The checkers observed that use of a halide-containing ether solution of methyllithium resulted in a considerable decrease in yield of the product, principally due to difficulty in following the subsequent procedure described in the text. 

A diethyl ether solution containing 20 mmoles of methyllithium is placed in a 50-mL reaction vessel equipped with a stopcock and standard taper joint. The vessel is attached to a vacuum line stopcock equipped with a mercury blow-out manometer,3 and the contents are frozen at -196° (liquid nitrogen) prior to evacuation of the vessel. 

All manipulations must be carried out in an inert atmosphere using standard Schlenk techniques and solvents that have been freshly distilled under nitrogen or argon. Methyllithium ( 5% solution in diethyl ether obtained from Ega Chemie or Aldrich) is standardized before use.4... 

The reaction is effected in ether solution at room temperature with an excess of the chlorosilane and is complete in less than 1 hour. After the ether solution has been washed with aqueous ammonium chloride, the quantity of the phenyltrimethylsilane produced can be determined. In practice, an aliquot of an ethereal solution containing excess chlorosilane and a known weight of the internal standard, cumene, is added to an aliquot of an ether solution of methyllithium or the methylmagnesium derivative. After the reaction is complete and the reaction mixture has been washed, the ether solution is separated and analyzed by gas chromatography. 

Styrene, benzene, and tetrahydrofuran were purified as described previously (8,11). Solutions of ec-butyllithium (Lithium Corporation of America, 12.0 wt % in cyclohexane) and methyllithium (Alfa, 1.45 M in ether) and lithium naphthalene were analyzed using the double titration procedure with 1,2-dibromoethane (12). Lithium naphthalene was prepared in tetrahydrofuran from lithium metal and a 25 mole % excess of sublimed naphthalene at -25°C using standard high vacuum procedures. Sealed ampoules of lithium naphthalene were stored in liquid nitrogen. 

A solution of methyllithium in ethyl ether may be purchased from Ventron Corporation. Directions for the preparation of ethereal methyllithium from methyl bromide are also available.4 The solution should be standardized before use by a titration procedure such as that of Watson and Eastham.5 6... 

The methyllithium is obtained as a 5% solution in diethyl ether. It is stored in a refrigerator at —20° until ready for use. The solution is standardized by measuring the amount of methane gas evolved when a sample is added to methanol. The gas analyses are carried out by hydrolyzing the sample on a standard vacuum line equipped with a Toepler pump.3... 

A solution of 110 mg. (0.83 mmoles) of 5ab in ether was added slowly to a solution of methyllithium (10% excess, Foote Chemical) in ether. The highly exothermic reaction was cooled in a room temperature water bath. Methane (39 ml.), ether vapor, and possibly carbon dioxide were collected [theoretical for proton abstraction reduction 19 ml. of methane]. After addition of ozonide was complete, the reaction was worked up in the same manner as the lithium aluminum hydride reduction. GPC analysis of the crude mixture revealed isopropyl alcohol (9) (>—60% by GPC standard) and 3-methyl-2-butanol (10) —60%). Methanol is normally produced in approximately the same yield (—60% ) as 9 and 10. We were unable to collect a sufiicient quantity from the labeling experiment for mass spectral analysis. Product identification was based on GPC retention times and by comparison of infrared spectra with those of authentic compounds. Mass spectral results were as follows isopropyl alcohol- assay 11.88% oxygen-18 3-methyl-2-butanol (10) assay 2.45%. 

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