Grignard reaction, acetophenone with

Reaction of racemic a-alkyl-a-(l H-1,2,4-triazol-l-yl)acetophenones with Grignard reagents in boiling diethyl ether affords exclusively the (RS/S -enantiomeric pairs. On the other hand, reaction of racemic a-alkoxy-x-(17/-l,2,4-triazol-l-yl)acetophenonc with Grignard reagents leads, under chelation control, to the (R/ /5S)-enantiomeric pair82. 

Organic molecules that contain sp2 hybridized carbons can also be prochiral if the substituent pattern is correct. An example is provided by phenylethanone (acetophenone, 9), which has three different groups attached to the carbonyl carbon. After reduction with, say, LiAlH4, the product is the chiral alcohol 10 and a 50 50 mixture of enantiomers is observed. The same racemic mixture is obtained from the reaction of the Grignard reagent MeMgBr with benzaldehyde (11). In contrast, the product of reduction of propanone (12) with LiAlH4 is propan-2-ol (13), which is not chiral. 

Mannich reaction of acetophenone with formaldehyde and piperidine results into the formation of an aminoketone, which on grignardization with bicyclic halide and subsequent neutralization with HCl affords the offieial eompound biperiden hydrochloride. 

Reaction of the Mannich product (112) from acetophenone itself with the Grignard reagent from p-chlorobcnzyl chloride gives the carbinol, 113. Dehydration in this case gives the antihistamine pyrrobutamine (114). It is not immediately clear why dehydration does not occur in the other sense so as to afford the energetically more favored stilbene. 

Reduction of the carbonyl function in acetophenones using sodium in ethanol also produces an alcohol. More complex aromatic alcohols may be prepared from carbonyl compounds by reaction with Grignard reagents followed by hydrolysis (see Chapter 10). 

In 1964, thanks to the development of modern techniques, especially electron-spin resonance (ESR), a direct proof could be given of the occurrence of radicals in the reaction of Grignard reagents, such as ethylmagnesium iodide, phenylmagnesium bromide, and /Jflra-tolylmagnesium bromide, in tetrahydrofuran (THF) with aromatic ketones, such as 4-chlorobenzophenone, 4-aminobenzophenone, 4-methoxybenzophenone, 4,4 -dimethoxybenzophenone, acetophenone, and 4-bromoacetophenone [34]. 

A comparison was made between the results of reactions of this allylic Grignard reagent and those of one-step Barbier reactions of allyl bromide and magnesium with three different substrates, i.e. benzophenone, acetophenone and carbon dioxide. 

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