Magnesium iodide-diethyl ether

The alkyl iodides and most of the alkyl bromides studied reacted with magnesium in diethyl ether at almost identical rates (see Fig. 3). As can be seen, the rate of the Grignard reagent was least sensitive to the structure of the organic halide. The difference between the structure-reactivity profiles for the Grignard reagent and the... 

Both pentafluorophenylmagnesium iodide and bromide have been reported (40-43). Apparently these reagents are readily formed from the appropriate halide and magnesium in diethyl ether. Pentafluorophenyl magnesium bromide has been used to prepare (C6Fs)4Si (32% yield) and (C,Fs)3P(39.5 % yield), as well as several pentafluorophenyltin compounds (Section V, C). 

To a mixture of 50 ml of dry THF and 0.050 mol of l-tert.-butoxy-2-pentyne (prepared by ethylation of HC-CCH O-tert.-Ci,H9 in liquid ammonia was added 0.055 mol of butyilithium in about 35 ml of hexane in 10 min at -30°C. After stirring for 20 min at -25°C the solution was cooled to -50°C and 0.06 mol of methyl iodide was added in one portion, followed 10 min later by 50 ml of water. The aqueous layer was separated and extracted twice with diethyl ether. The solutions were dried over magnesium sulfate and concentrated in a water-pump vacuum. 

Barbier reported (1) in 1899 that a mixture of methyl iodide, a methyl ketone, and magnesium metal in diethyl ether produced a tertiary alcohol. Detailed studies by his student Victor Grignard are documented in his now classical doctoral thesis, presented in 1901. Grignard estabUshed (2) that the reaction observed by Barbier could be separated into three distinct steps Grignard reagent formation, Grignard reaction, and hydrolysis. 

There are five components to the cost of using a Grignard reagent (/) magnesium metal, (2) the haUde, (J) the solvent, (4) the substrate, and (5) disposal of the by-products. The price of magnesium in mid-1992 was 3.20/kg, having risen from 1.20/kg in 1966 to 1.36/kg in 1970 and 2.90/kg in 1979. Prices for tetrahydrofuran and diethyl ether, the two most commonly used solvents, have also increased (Table 3) in the same period. The cost of the hahde depends on its stmcture, but as a general rule the order of cost is chloride < bromide < iodide. 

For a-benzyloxycyclohexaneacelaldehyde and 2-butenylstannanes, good chelation control was observed using zinc iodide and titanium(IV) chloride, but only weak synjanti selectivity. Better syn/anti selectivity was found using boron trifluoride-diethyl ether complex, but weak chelation control. Magnesium bromide gave excellent chelation control and acceptable syn/anli selectivity90. 

The reaction of isopropylidene piperidinomethylenemalonate and methyl magnesium iodide in a mixture of diethyl ether and THF at room temperature gave isopropylidene ethylidenemalonate in 92% yield (88JA1880) (Scheme 58). 

The preparation of a Grigncird reagent begins with magnesium metal and dry ether (in most cases, either diethyl ether or THF, tetrahydrofuran). The ether cleans the surface of the metal and takes the reagent into solution for reaction. (If either the ether or the reaction vessel contains moisture, the yield is poor.) The magnesium then reacts with either an alkyl halide or an aryl halide. The ease of reactivity decreases in the order R1 > RBr > RCl. Iodides may react too rapidly, but chlorides may react too slowly. Thus bromides are usually the best. The general reaction is... 

To a solution of 6.7 g of sodium amide in 100 ml of anhydrous diethyl ether was added dropwise 26 g of 4-isobutylbenzene cyanide while the mixture was stirred and heated under gentle reflux. After all of the 4-isobutylbenzene cyanide had been added, the mixture was heated under gentle reflux for 15 min, after which 23.4 g of ethyl iodide was slowly added dropwise thereto from the dropping funnel. After completion of the addition of the ethyl iodide, the mixture was heated under gentle reflux for an initial period of 15 min, after which it was diluted with an equal volume of water and shaken. The two layers that formed were separated and the aqueous layer was then extracted with two 50 ml portions of diethyl ether. The ether extracts were combined and then washed with two 80 ml portions of water and dried over anhydrous magnesium sulfate. The dried ether extract was then distilled at a subatmospheric pressure. In this manner, 25 g of a clear transparent uncolored liquid having a boiling point of 118-122°C at a pressure of 1mm of mercury, which consisted of 2-(4-isobutylphenyl)butyronitrile, was collected. This yield was equivalent to 83% of the theoretical. 

Methyl Phenylethynyl Tellurium1 An apparatus suitable for work with liquid ammonia is set up. Sodium amide is prepared in a 1 -l flask by adding 6.0 g (0.26 mol) of sodium to 250 ml of liquid ammonia, than 25 g (0.25 mol) of phenylacetylene are added dropwise. 30 g (0.24 mol) of tellurium powder are added over 20 min in small portions to the well-stirred sodium amide solution. 36 g (0.25 mol) of methyl iodide are added dropwise over 10 min to the tellurolate solution. The ammonia is then evaporated, the residue is extracted with diethyl ether, the extract is washed with water and the organic phase dried with anhydrous magnesium sulfate. The ether is distilled off and the residue fractionally distilleed under vacuum yield 28 g (48%) b.p. 122-12472 torr (0,267 kPa). 

Formylphenyl Methyl Tellurium1 20 g (0.05 mol) of 2-formylphenyl dimethyl telluronium iodide are dissolved in 100 m/of pyridine and the solution is heated under reflux for 3 h. The solution is then cooled and poured into a mixture of ice and dilute hydrochloric acid. The mixture is extracted with diethyl ether, the extract is washed with water, dried with magnesium sulfate, the solvent is distilled off, and the residue is fractionally distilled under vacuum yield 9.8 g (77%) b.p. 120 13070.1 torr (13.3 Pa). 

Diaryl tellurium dihalides in toluene solutions reacted with aryl magnesium bromides in diethyl ether to yield triaryl telluronium salts in yields ranging from 6 to 78% (Vol. IX, p. 1082/3)3-5. Aqueous solutions of the products were generally treated with potassium iodide to convert the telluronium halides to telluronium iodides3,4. 

Diphenyl Naphthyl Telluronium Iodide1 10 g (28 mmol) of diphenyl tellurium dichloridc are dissolved in 250 ml of dry toluene. A solution of 1 -naphthyl magnesium bromide in diethyl ether is prepared from 17.4 g (84 mmol) of 1-bromonaphthalene. The solution of the tellurium compound is quickly poured into the freshly prepared Grignard solution, the mixture is shaken vigorously, and 20 ml of dilute hydrochloric acid are added immediately. The solution is decanted from the precipitate, the precipitate is dissolved in boiling water, silver chloride is added, and the mixture is heated. The mixture is then filtered, sodium sulfite is added to the filtrate, and the telluronium iodide is precipitated by the addition of potassium iodide yield 11.8 g (78%) m.p. 148° (from ethanol, ethanol/diethyl ether). 

The first preparation, of cyclomagnesium chloride, exemplifies the traditional procedure [29], using magnesium turnings, with diethyl ether as the solvent, and no provision of an inert atmosphere other than the solvent vapour. This type of procedure is satisfactory for most primary and many secondary and tertiary alkyl chlorides and bromides and for many aryl bromides. Iodides may also be used, but the additional expense is rarely justified, particularly as they tend to suffer more side-reactions such as Wurtz-type coupling. Early work on the factors affecting such reactions has been thoroughly reviewed [A],... 

To magnesium (1.4g) slurried in 18ml THF was added a small crystal of iodine, 1 drop of methyl iodide and 0.1 ml of vinyl bromide. This was followed by an additional 4 ml vinyl bromide dissolved in 9 ml THF, and the mixture stirred for 1 hour at 50 °C. The mixture was cooled to 0 to -5 °C, the product from Step 2 (8 g) dissolved in 32 ml THF added, stirred 3 hours at ambient temperature, then re-cooled to 0-5 °C. NH4CI (4.2 g) dissolved in 10 ml water was added, the mixture stirred 10 minutes, extracted with diethyl ether, washed with water, dried, concentrated, and 9 g of product isolated. 

To a suspension of cuprous iodide (0.03 mol) in 100 ml THF was added 25 ml dimethyl sulfide. The solution was cooled to -78 °C, phenyl magnesium bromide (0.06 mol) dissolved in diethyl ether added, stirred one hour, and 2-cyclohexenone (0.03 mol) dissolved in 10 ml THF added. The mixture was warmed to 0°C over 2 hours then re-cooled to -78 °C. It was treated with 15 ml hexamethyl-phosphoramide, stirred 30 minutes, treated with methyl cyanoformate (0.09 mol), and warmed to ambient temperature overnight. The mixture was poured into 100 ml 2M HCl, the organic phase separated, and the aqueous phase extracted with CH2CI2. The combined organic extracts were concentrated, the residue triturated with NH4CI, water, brine, dried, and 3.2 g product isolated as an oil. 

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