Grignard reagents ethyl orthoformate

RCHO + RCHO —> RCOOCHjR 3. From ethyl orthoformate and the Grignard reagent, for example CsH aMgBr + CH(0C3H3)3 —... 

Grignard reagents can also act as sources of negative carbon in displacement reactions, e.g. in the synthetically useful reaction with triethoxymethane (ethyl orthoformate, 58) to yield acetals (59) and, subsequently, their parent aldehydes (60) ... 

From ethyl orthoformate and the Grignard reagent, for example ... 

The preparation of acetals is effected by refluxing an ethereal solution of ethyl orthoformate and a Grignard reagent. Prolonged heating is necessary for maximum yields. The reaction mixtures are then carefully processed by the addition of ice and dilute acetic acid followed by extraction with ether and distillation to give the acetal (80-90%). Further studies have been made in conjunction with the preparation of aldehydes (method 165). ... 

The reaction of ethyl orthoformate and Grignard reagents gives acetals which are hydrolyzed readily by dilute acid to aldehydes. This method has been employed extensively for the preparation of aliphatic and aromatic aldehydes. A study of the optimum conditions has been made, using the conversion of bromobenzene to benzaldehyde as a model synthesis (90%), Comparative studies of various aldehyde syntheses that employ Grignard reagents (methods 154, 166, and 167) show that this one is the most practical however, the possibility of a sudden exothermic reaction limits the size of the run. Longer reaction times at room or reflux tempjerature help overcome this difficulty. Examples of the better preparative procedures are found in those for -hexaldehyde (50%), p-tolualdehyde (TS ), " and phenanthrene-S>-aldehyde (42%)." ... 

Apart from the technical route described to p-apo-8 -carotenal, readily available vitamin A alcohol (Cjo) has served as an intermediate in the form of the phosphonium salt by reaction with the monodiethyl acetal of a Cio dial (ref. 54). The required Cjo monodiethylacetal was obtained (ref.5, p409) by the reaction of the mono aldehyde-protected derivative, the enol ether of methylmalonaldehyde, (C4) with the acetylenic Grignard reagent from trans 3-methyl-2-penten-4-yn-l-ol (C ) followed by acidic dehydration and partial reduction with Lindlar catalyst to give firstly 8-hydroxy-2,6-dimethylocta-2, 4,6-triene-l-al (Cio). Protection of the hydroxyl group by acetylation in pyridine solution with acetyl chloride and formation of the diethyl acetal with ethyl orthoformate followed by hydrolysis of the acetyl group and oxidation afforded the final CIO aldehyde component (D)shown in Scheme 15a. 

The procedure given for the preparation of phenylpropargyl aldehyde is a modification of Claisen s directions3 in part due to Kalff.4 The monobromocinnamic aldehyde was described by Zincke.8 Other methods of possible preparative value for the acetal are the interaction of sodium phenyl acetylene,6-9 or the Grignard reagent from phenylacetylene,10 11 and ethyl orthoformate. 

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