Ethyl bromide : Grignard

Triphenyl-carbinol, (C6H5)3COHy from Ethyl Benzoate and Phenyl Magnesium Bromide. (Grignard Reaction 6 (a).)... 

Vote 2. A large excess of R MgCl is required, as the subsequent metallation of the enyne is rapid. In the case of C2H5 the Grignard reagent was prepared from ethyl bromide. 

The halogen influences the rate of reaction, and, in general, the order of reactivity is HI > HBi > HCl. Impoitant uses of etfiyl chloiide include the manufacture of tetraethyllead and ethylceUulose. Ethyl bromide can be used to produce ethyl Grignard reagent and various ethyl amines. 

A solution of 6.3 g (0.9 moles) ethoxyacetylene in 50 ml ether is added dropwise during 30 min to a Grignard reagent prepared from 2.18 g (90 mg-atoms) magnesium and 9.81 g (90 mmoles) ethyl bromide. The reaction mixture is stirred for 1 hr at room temperature and then a solution of 3 g (9 mmoles) 3) -acetoxyandrost-5-en-I7-one in 50 ml dry ether is added dropwise. The mixture is refluxed for 1 hr and after cooling to 0° poured into 100 ml of an aqueous ammonium chloride solution. The aqueous solution is extracted with ether, and the organic extract is washed with ammonium chloride solution and water, dried, and evaporated. The residue is chromatographed on 130 g alumina (activity III). Elution with petroleum ether-benzene (1 1) yields, after crystallization from acetone-hexane, 1.27 g (35%) 3j5-acetoxy-17a-ethoxyethynylandrost-5-en-17) -ol mp 138-139° Ho -122°. 

The usefulness of the Grignard reagent of 3-bromothiophene is somewhat limited as it can only be prepared by the entrainment method. The simultaneous formation of Grignard reagents from 3-bromothiophene and a fivefold molar excess of ethyl bromide gave, however, a 55% yield of 3-thiophenecarboxylic acid upon carbona-tion. With acetaldehyde, a 55% yield of methyl 3-thienyl carbinol... 

One approach (.40) has been to conduct the reaction in the presence of a more electropositive metal, often as an alloy. In the presence of magnesium, tin reacts with ethyl bromide to give tetraethyl tin, and various additives promote the reaction, the sequence of effectiveness being carbitols I > tetrahydrofuran, tetrahydrothiophene > ether triethylamine Br the ions ClOj, PFg, BFj, and BPhj are without effect. It is suggested that this reflects the coordination of the additive (L) to the Grignard reagent that is first formed, making it more reactive towards metallic tin. 

Next to the formation of Grignard reagents, the most important application of this reaction is the conversion of alkyl and aryl halides to organolithium compounds, but it has also been carried out with many other metals, (e.g., Na, Be, Zn, Hg, As, Sb, and Sn). With sodium, the Wurtz reaction (10-93) is an important side reaction. In some cases, where the reaction between a halide and a metal is too slow, an alloy of the metal with potassium or sodium can be used instead. The most important example is the preparation of tetraethyl lead from ethyl bromide and a Pb—Na alloy. 

Ethylene bromide has been demonstrated to be as efficient as ethyl bromide as an entrainment agent.9 Its use is advantageous because a second Grignard reagent is not introduced in the reaction mixture—only magnesium bromide. An additional feature of this preparation and of most preparations involving entrainment agents is the slow rate of addition of the entrainer, which... 

Mix 294g (1.6M) 1,3,5-trichlorobenzene, 184g (3.4M) Na methoxide and 450g (3 3M) diglyme and reflux at 162° C for 42 hours. Cool to room temperature, filter and distill the solvent to get 70% yield of l-Cl-3,5-dimethoxybenzene (I). 43.2g (I) in 540 ml tetrahydrofuran is added dropwise to 7.3g Mg, a small crystal of iodine and a few drops of ethyl bromide (under nitrogen if possible) over Vi hour while the mixture is heated to 75° C. Reflux 2 hours and cool to room temperature to obtain the Grignard solution. 

Methyl Bromide.—The simplest alkyl bromide is prepared in an esentially similar way (Bygden, J. pr. Ghem., 1911, 83, 421). Since it boils at 4-5° it is difficult to keep in stock, but its direct application in the Grignard reaction, in place of the dearer iodine compound, is very much to be recommended. Uses analogous to those of ethyl bromide. 

Sonawane et al. (Sonawane et al., 1994) described a practical and efficient synthesis of fenoprofen using commercially available m-phenoxybenzaldehyde as the starting material. The key step in the synthesis is the transformation of the a-hydroxyacetal (i) into its chlorosulfonyl ester in situ and its concomitant rearrangement to the methyl ester (ii) in high yields. The required a-hydroxyacetal (i) can be readily prepared from m-methoxybenzaldehyde by the routine sequence of reactions Grignard reaction with ethyl bromide or chloride, oxidation and finally a-chlorination with CuCI2-LiCI/DMF. 

Tris(y-trifluoropropyl)chlorosilane is synthesised in three stages. First of all, tris(y-trifluoropropyl)silane is obtained by the Grignard technique in the dibutyl ether medium in the presence of a catalyst, ethyl bromide ... 

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