Methyllithium, ether solution

A 2 L three-necked flask equipped with a dropping funnel and magnetic stirrer is charged with 250 ml of ether and 130.3 g (0.50 mol) of TiCl(OPr)3 (9) and cooled to -40 °C. The equivalent amount of methyllithium (ether solution) is slowly added and the solution allowed to come to room temperature within 1.5 h. The solvent is removed in vacuo and the yellow product distilled directly from the precipitated lithium chloride at 48-53 °C/0.01 Torr 113 g (94% yield) ... 

Anionic polymerization of vinyl monomers can be effected with a variety of organometaUic compounds alkyllithium compounds are the most useful class (1,33—35). A variety of simple alkyllithium compounds are available commercially. Most simple alkyllithium compounds are soluble in hydrocarbon solvents such as hexane and cyclohexane and they can be prepared by reaction of the corresponding alkyl chlorides with lithium metal. Methyllithium [917-54-4] and phenyllithium [591-51-5] are available in diethyl ether and cyclohexane—ether solutions, respectively, because they are not soluble in hydrocarbon solvents vinyllithium [917-57-7] and allyllithium [3052-45-7] are also insoluble in hydrocarbon solutions and can only be prepared in ether solutions (38,39). Hydrocarbon-soluble alkyllithium initiators are used directiy to initiate polymerization of styrene and diene monomers quantitatively one unique aspect of hthium-based initiators in hydrocarbon solution is that elastomeric polydienes with high 1,4-microstmcture are obtained (1,24,33—37). Certain alkyllithium compounds can be purified by recrystallization (ethyllithium), sublimation (ethyllithium, /-butyUithium [594-19-4] isopropyllithium [2417-93-8] or distillation (j -butyUithium) (40,41). Unfortunately, / -butyUithium is noncrystaUine and too high boiling to be purified by distiUation (38). Since methyllithium and phenyllithium are crystalline soUds which are insoluble in hydrocarbon solution, they can be precipitated into these solutions and then redissolved in appropriate polar solvents (42,43). OrganometaUic compounds of other alkaU metals are insoluble in hydrocarbon solution and possess negligible vapor pressures as expected for salt-like compounds. 

Although ethereal solutions of methyl lithium may be prepared by the reaction of lithium wire with either methyl iodide or methyl bromide 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. Certain of the ethereal solutions of methyl 1ithium 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 dimethyl cuprate or the use of methyllithium in 1,2-dimethyoxyethane to prepare lithium enolates from enol acetates or triraethyl silyl enol ethers, the presence of this lithium salt interferes with the titration and use of methyllithium. There is also evidence which indicates 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. For these reasons it is often desirable to have ethereal solutions... 

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 mole percent 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 by Aldrich Chemical Company these solutions have a limited shelf-life and older solutions have often deteriorated... 

The dry tosylhydrazone (20 g, 45.5 mmol) is dissolved in 750 ml of 1,2-dimethoxyethane (freshly distilled from lithium aluminum hydride) in a flame-dried 1 liter round bottom flask fitted with a 240 ml addition funnel, a drierite tube and a magnetic stirrer. A 2.05 M ether solution of methyllithium (130 ml, Alfa Inorganics, Inc.—Caution to avoid the mineral oil impurity the methyllithium solution is decanted from a cold solution which contains a precipitate) is placed in the dropping funnel and added over a 60 min period. The temperature of the reaction mixture increases to ca. 35° during the addition however, no cooling precautions are required. The highly colored reaction mixture is stirred for 7 hr and then poured into 1.5 liters of ice water. The flocculent precipitate is digested for 12 hr at room temperature to speed the filtration. After filtration the filter cake is washed with 500 ml water and dried under vacuum at 50° for several hr. The androsta-5,16-dien-3l5-ol is obtained in ca. 70% yield after recrystallization from methanol mp 138-139°. 

An ethereal solution approximately 2.5 molar in methyllithium is prepared from 17 ml of methyl iodide and 4 g of lithium metal in 200 ml of anhydrous ether. A mixture consisting of 150 ml anhydrous ether, 3 g (10 mmoles) of 3jS-hydroxy-5a-androstane-ll,17-dione and 60 ml (0.15 moles) of the above methyllithium solution are stirred at room temperature for 40 hr. The reaction mixture is diluted with 100 ml of water and the ether is removed by distillation. Filtration of the chilled aqueous phase yields 2.6 g (77%) of 1 la,17a-dimethyl-5a-androstane-3a,l l/ ,17j5-triol mp 149-154°. Recrystallization from acetone-hexane yields pure material mp 164-166° [a] —5° (CHCI3). 

Methyllithium in ether solution is available from Foote Mineral Company. 

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. 

When one equivalent of cuprous iodide was treated with one equivalent of methyllithium the yellow, ether-insoluble product was formed. Both the precipitate and the ether solution... 

An ethereal solution of methyllithium was either prepared from lithium metal and methyl bromide or purchased from Alfa Inorganics, Inc. Concentrations of 0.5-2M were used with no change in result. 

An ethereal solution which was 1.38ilf in methyllithium was purchased from Foote Mineral Company. The concentration of methyllithium in ethereal solutions may be conveniently determined by a procedure described elsewhere in which the lithium reagent is titrated with 5ec-butyl alcohol, utilizing the charge transfer complex formed from bipyridyl or o-phenanthro-line and the lithium reagent as an indicator. 

B. 2-Benzyl-2-methylcyclohexanone. Caution Ethereal solutions of methyllithium in contact with atmospheric oxygen may catch fire spontaneously. Therefore any manipulntions milk this reagent must he carried out with the utmost care to avoid accidental... 

Ethereal solutions of methyllithium are available from either Foote Mineral Company or Alpha Inorganics, Inc. These solutions should be titrated immediately before use with 2-butanol and 2,2-bipyridyl as an indicator. In a typical run, 2.44 ml. of ethereal 1.64iH methyllithium was employed. 

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. 

The gem-dibromocyclopropanes are treated with an etheral solution of either methyllithiura or n-butyllithium at 0° to — 80°C. Methyllithium is preferable to /2-butyllithium because occasionally difficulties are encountered in completely separating the n-butyl bromide from the allene product. 

In the third step an ethereal solution of the step 2 product was added to a solution of either 2.3 ml methyllithium (1.4 M in diethyl ether), 1.75 ml phenylmagnesium chloride (2 M in THF), or 7 ml of pentafluorophenylmagnesium chloride (0.5 M in diethyl ether). The reaction mixture was then slowly warmed to ambient temperature and stirred for 4 hours. The salt that formed was filtered and the filtrate concentrated. The residue was recrystallized from ether/pentane and the catalyst isolated from between 60 and 70% yield. 

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... 

Diethyl ether and toluene (both BDH, GPR grade) are dried and freed of dissolved molecular oxygen by distillation under nitrogen from a solution of the solvent and sodium benzophenone. Anhydrous indium trichloride (Aldrich) and an ethereal solution of methyllithium (Aldrich) are used as supplied dppe (Fluorochem) is also used as supplied. Anhydrous gallium trichloride (Aldrich) is sublimed before use. 

---