Grignard compounds reactions

Another area of interest to the industrial sector is the development of a more efficient synthesis of biaryl compounds. This has been accompHshed using a Ni(II)-cataly2ed Grignard coupling reaction with an aryl haUde (86—89). 

Benzyl chloride readily forms a Grignard compound by reaction with magnesium in ether with the concomitant formation of substantial coupling product, 1,2-diphenylethane [103-29-7]. Benzyl chloride is oxidized first to benzaldehyde [100-52-7] and then to benzoic acid. Nitric acid oxidizes directly to benzoic acid [65-85-0]. Reaction with ethylene oxide produces the benzyl chlorohydrin ether, CgH CH20CH2CH2Cl (18). Benzylphosphonic acid [10542-07-1] is formed from the reaction of benzyl chloride and triethyl phosphite followed by hydrolysis (19). 

Diazirines (3) smoothly add Grignard compounds to the N—N double bond, giving 1-alkyldiaziridines. Reported yields are between 60 and 95% without optimization (B-67MI50800). The reaction is easily carried out on a preparative scale without isolation of the hazardous diazirines and may serve as an easy access to alkylhydrazines. The reaction was also used routinely to detect diazirines in mixtures. The diaziridines formed are easily detected by their reaction with iodide. Phenyllithium or ethylzinc iodide also add to (3) with diaziridine formation. 

Diazirine, fluoromethoxy-nitrogen extrusion, 7, 224 Diazirine, methylvinyl-rearrangement, 7, 221 Diazirines addition reactions to Grignard compounds, 7, 2 0 as carbene precursors, 7, 236 IR spectra, 7, 203 microwave spectrum, 7, 199 molecular spectra, 7, 202-204 nitrogen extrusion, 7, 223 NMR, 7, 202 photoconversion to diazoalkanes, 7, 234 photoisomerization, 7, 221 photolysis, 7, 225-227 quantum chemical investigations, 7, 197 reactions... 

A modern variant is the intramolecular magnesium-ene reaction, e.g. the reaction of the alkene-allylic-Grignard compound 9 to give the five-membered ring product 10. This reaction proceeds regio- and stereoselectively, and is a key step in a synthesis of the sesquiterpenoid 6-protoilludene ... 

Since the formation of the Grignard compound takes place at the metal surface, a metal oxide layer deactivates the metal, and prevents the reaction from starting. Such an unreactive metal surface can be activated for instance by the addition of small amounts of iodine or bromine. 

Organic halides play a fundamental role in organic chemistry. These compounds are important precursors for carbocations, carbanions, radicals, and carbenes and thus serve as an important platform for organic functional group transformations. Many classical reactions involve the reactions of organic halides. Examples of these reactions include the nucleophilic substitution reactions, elimination reactions, Grignard-type reactions, various transition-metal catalyzed coupling reactions, carbene-related cyclopropanations reactions, and radical cyclization reactions. All these reactions can be carried out in aqueous media. 

In 1991, Li and Chan reported the use of indium to mediate Barbier-Grignard-type reactions in water (Eq. 8.49).108 When the allylation was mediated by indium in water, the reaction went smoothly at room temperature without any promoter, whereas the use of zinc and tin usually requires acid catalysis, heat, or sonication. The mildness of the reaction conditions makes it possible to use the indium method to allylate a methyl ketone in the presence of an acid-sensitive acetal functional group (Eq. 8.50). Furthermore, the coupling of ethyl 2-(bromomethyl)acrylate with carbonyl compounds proceeds equally well under the same reaction conditions, giving ready access to various hydroxyl acids including, for example, sialic acids. 

Because in the case of a sterically crowded imidazolide the formation of a carbinol is more difficult, reaction with the titanium reagent or the corresponding Grignard compound produces the allyl ketone in about the same yield [96]... 

If the formation of the Grignard compound proceeds too violently the reaction product usually contains considerable amounts of diphenyl because of the reaction ... 

The Grignard compounds react with varying ease with organic halides in the manner of the Wurtz reaction according to the equation ... 

The Mannich reaction of secondary amines R NH (dibenzylamine, piperidine, morpholine, etc.), aldehydes R2CHO (R2 = alkyl, Ph or 2-furyl) and thiols R3SH (R3 = alkyl, Ph or benzyl) results in a-amino sulphides, which react with Grignard compounds to give tertiary amines in good yields (equation 47)136. 

High yields of -substituted allenic primary amines 227 are obtained by the CuBr-Me2S-or NiCh Ph2PCH2CH2CH2PPh2-catalysed reaction of the acetylene derivative 226 with aryl Grignard compounds and subsequent deprotection by flash chromatography219. 

Grignard compounds in the thiophene series were studied (20) and used for the synthesis of some thienylbutenols. The product obtained by the reaction of alpha-thienylmagnesium bromide with butadiene monoxide has been identified as 4-(2-thienyl)-buten-2-ol-l formed by 1-4 addition. Furthermore, the Grignard compounds were utilized for... 

No reaction at all, either with Aei-osil or its chloride, was observed with Grignard compounds. 

Determinations of active hydrogen with methyllithium and with methylmagnesium iodide were undertaken by Uytterhoeven and Fripiat (366). Only after outgassing at 600° or higher, did the results of both methods agree with each other and with the weight loss on calcination. The reactions proceeded more slowly than with Aerosil silica (195). Apparently, diffusion into the pores is hindered, especially with the Grignard compound. 

Addition of organometallic reagents to nitro compounds is possible but is sparingly used. Reaction of aromatic nitro compounds with large excess of phenyl magnesium bromide produces hydroxylamines in moderate yield . Similar addition of Grignard compounds to nitromethane proceeds in low yield ° while addition of excess methyllithium to tertiary nitro compound 113 results in formation of hydroxylamine 114 (equation 83) . ... 

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