Methylmagnesium bromide

A solution of methylmagnesium bromide in 150 ml of diethyl ether, prepared from 0.5 mol of methyl bromide (see Chapter II, Exp. 5) was subsequently added in 20 min with cooling at about 20°C. After the addition the mixture was warmed for 2 h under reflux (the thermometer and gas outlet were replaced with a reflux condenser), a black slurry being formed on the bottom of the flask. The mixture was cooled in a bath of dry-ice and acetone and a solution of 30 g of ammonium chlori.de in 200 ml of water was added with vigorous stirring. The organic layer and four ethereal extracts were combined, dried over potassium carbonate and subsequently concentrated in a water-pump vacuum. Careful distillation of the residue through a 40-cm... 

The reaction of l,4-bis(trimethylsilyl)-l,3-butadiyne (174) with disilanes, followed by treatment with methylmagnesium bromide, produces i,l,4,4-tetra(-trimethylsilyl)-l,2,3-butatriene (175) as a major product[96]. The reaction of octaethyltetrasilylane (176) with DMAD proceeds by ring insertion to give the six-membered ring compounds 177 and 178[97], The l-sila-4-stannacyclohexa-2,5-diene 181 was obtained by a two-step reaction of two alkynes with the disilanylstannane 179 via the l-sila-2-stannacyclobutane 180[98],... 

Make a molecular model of 7 7 dimethylbicyclo[2 2 l]heptan 2 one Two diastereomenc alcohols may be formed when it reacts with methylmagnesium bromide Which one is formed in greater amounts ... 

Smid and coworkers have developed a straightforward and effective method for the synthesis of 4 -vinylbenzo-15-crown-5. In this method, 3,4-dihydroxybenzaldehyde is converted into the crown in the usual fashion and then the side chain is transformed by successive treatment with methylmagnesium bromide and then toluenesulfonic acid to effect dehydration. The overall yield is about 20%. 

Reaction of 17j -acetoxy-3,3-ethylenedioxy-5a-androstan-l-one (1) with methylmagnesium bromide followed by treatment with acid and reacetylation affords the 1-methyl-A -3-ketone (3). The configuration of carbon-1 of the intermediate (2) has not been established/ ... 

Addition of methylmagnesium bromide or methyllithium to 21-acetoxy-3,3 20,20-bisethylenedioxy-17a-hydroxypregn-5-ene-7,l 1-dione and subsequent acid treatment affords 7-methyl-A -cortisone. ... 

The 11-keto group is relatively difficult to attack, due to steric hindrance. However, reaction of 3j -hydroxy-5a-androstane-l 1,17-dione (37) with methylmagnesium bromide at 25° unexpectedly gives a 30% yield of 1 la,17a-dimethyl-5a-androstane-3j5,lljS,17i -triol (38) in addition to the 17-monomethyl product (39). 

The 17i -hydroxy-16-ketone (47) on treatment with methylmagnesium bromide provides the 16a-methyl compound (48). ... 

The addition of methylmagnesium bromide to 3j -acetoxy-D-homo-androst-5-en-17a-one (52) proceeds with formation of the equatorial 17a/5-methyl carbinol (53), a result which is analogous to the previously described alkylations of 12-keto steroids. 

The reaction of (54) and acetylenedimagnesium bromide, prepared from methylmagnesium bromide and acetylene, gave (55) in excellent yield instead of the expected bis-steroid (57). 

The C-20 epimeric diacetates (69) and (70) are obtained in a total yield of 30% by acetylation of the mixture formed from 21-acetoxy-3j -hydroxy-pregn-5-en-20-one (68) with methylmagnesium bromide. ... 

Bromination of the enolate anion from the reaction of 3j -acetoxypregna-5,16-dien-20-one (1) with methylmagnesium bromide in the presence of cuprous chloride affords (after treatment with sodium iodide to dehalo-genate any 5,6-dibromide) a mixture of 17a-bromo- and 17)5-bromo-16a-methyl compounds (11) and (12) in a ratio 9 1. The 17a-iodides can be obtained in an analogous reaction. 

When a fourfold excess of methylmagnesium bromide and catalytic amounts of cuprous chloride in tetrahydrofuran are employed, the reaction proceeds within 30 minutes at room temperature. Under these conditions the A -l-methyl-5a-3-ketone (15) affords the 1,1-dimethyl compound (16) in 50% yield after reacetylation. The A -l-methyl-3-methylene steroid (17) is also isolated in 23% yield. 

In the estrone series diaxial cleavage of the 6a,7a-epoxide (10) with methylmagnesium bromide affords (11) in 60% yield. ... 

The 16a,l7a-epoxide (12) can be made to react with methylmagnesium bromide or methyllithium as well as phenyllithium to yield (13a) and (13b), respectively, after ketal cleavage. 

A total of 50 ml (0.15 moles) of a 3 ethereal solution of methylmagnesium bromide is added slowly to a vigorously stirred solution of 5.8 g (12.5 mmoles) or 3,3 20,20-bisethylenedioxy-5a,6a-epoxy-5a-pregnane-ll/l,17a,21-triol in 400 ml of tetrahydrofuran. The solution is heated under reflux for 24 hr, cooled and treated with 32 ml of saturated ammonium chloride solution. The supernatant is decanted and the residue is washed with several portions of tetrahydrofuran. The combined supernatants are evaporated and extracted with ethyl acetate, washed with saturated salt solution, dried and concentrated to give 4,55 g (75%) of 3,3 20,20-bisethylenedioxy-6 -methyl-5a-pregnane-5a,ll, 17a,21-tetrol mp 170-172° after crystallisation from acetone-petroleum ether. The analytical sample is crystallized from acetone-petroleum ether mp 175-177° [aJo —11° (CHCI3). 

When planning the synthesis of a compound using an organometallic reagent, or indeed any synthesis, the best approach is to reason backward from the product. This method is called retrosynthetic analysis. Retro-synthetic analysis of 1-methylcyclohexanol suggests it can be prepared by the reaction of methylmagnesium bromide and cyclohexanone. 

The actual mechanism by which a particular reaction proceeds strongly depends on the nature of the organomagnesium reagent. For instance benzophenone reacts with methylmagnesium bromide by a polar mechanism, while the reaction with t-butylmagnesium chloride proceeds for steric reasons by a SET-mechanism. 

Alternatively, as described in U.S. Patent 3,341,557, 6-dehydro-17-methyltestosterone may be used as the starting material. A mixture of 0.4 g of cuprous chloride, 20 ml of 4 M methylmagnesium bromide in ether and 60 ml of redistilled tetrahydrofuran was stirred and cooled in an ice bath during the addition of a mixture of 2.0 g of 6-dehydro-l 7-methyl-testosterone, 60 ml of redistilled tetrahydrofuran and 0.2 g of cuprous chloride. The ice bath was removed and stirring was continued for four hours. Ice and water were then carefully added, the solution acidified with 3N hydrochloric acid and extracted several times with ether. The combined ether extracts were washed with a brine-sodium carbonate solution, brine and then dried over anhydrous magnesium sulfate, filtered and then poured over a 75-g column of magnesium silicate (Florisil) packed wet with hexanes (Skellysolve B). The column was eluted with 250 ml of hexanes, 0.5 liter of 2% acetone, two liters of 4% acetone and 3.5 liters of 6% acetone in hexanes. 

Nitriles (RC=N) react with Grignard reagents (R MgBr). The reaction produc from 2-methylpropanenitrile with methylmagnesium bromide has the fol lowing spectroscopic properties. Propose a structure. 

Phenyl-2-butanol has a methyl group, an ethyl group, and a phenyl group (—Cgl ) attached to the alcohol carbon atom. Thus, the possibilities arc addition of ethylmagnesium bromide to acetophenone, addition of methylmagnesium bromide to propiophenone, and addition of phenylmagnesimn bromide to 2-butanone. 

Starting from an ester, the only possibility is addition of methylmagnesium bromide to an ester of butanoic acid, such as methyl butanoate. 

Show the products obtained from addition of methylmagnesium bromide to the following compounds ... 

The teal value of the Wittig reaction is that it yields a pure alkene of defined structure. The C=C bond in the product is always exactly where the OO group was in the reactant, and no alkene isomers (except E,Z isomers) are formed. For example, Wittig reaction of cyclohexanone with methylenetriphenyl-phosphorane yields only the single alkene product methylenecyclohexane. By contrast, addition of methylmagnesium bromide to cyclohexanone, followed by dehydration with POCI3, yields a roughly 9 1 mixture of two alkenes. 

Thiocarbonyl tetrachloride, 46, 21 m Thiocresol (Warning), 47, 107 Thionyl chloride, 46, 16 98 Thiophosgene 46, 21 Thiophosphoryl chloride, reaction with methylmagnesium bromide to i lelci tetramethylbiphosphine disulhdc 46,102... 

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