Dichlorocarbene reaction with benzaldehyde

When the reaction with substituted benzaldehydes is conducted in the presence of ammonia, the a-amino carboxylic acids are formed [11], The corresponding reaction involving bromoform is less effective and, for optimum yields, the addition of lithium chloride, which enhances the activity of the carbonyl group, is required. In its absence, the overall yields are halved. The reaction of dichlorocarbene with ketones or aryl aldehydes in the presence of secondary amines produces a-aminoacetamides [12, 13] (see Section 7.6). 

An interesting result is given in a paper provided by this group on the reaction of benzaldehyde with dichlorocarbene generated in situ from chloroform and solid NaOH under sonication in the presence of PTC [43]. Normally a-hydroxybenzoic acid is the additional product in this reaction [44], but under sonication, benzoic... 

Carbene reaction under PTC conditions. Reaction of dichlorocarbene generated from chloroform and alkali with benzaldehyde to yield mandelic acid. Subsequent hypochlorite oxidation of methyl mandelate and esterification to form metamitron. 

At this point a benzaldehyde dimethylaeetal is used for the acetah-/ation. The thermodynamically favored six-membered acetal 15 is formed preferentially over the potential competitors five- and sev-cn-membereil acetals5 (See Chapter 7). Transformation of a primary alcohol function into the triflate group of structure 16 must precede the Sn2 reaction in the third step, in which a carbon nucleophile is created with LDA and chloroform. Dcprolonalion of chloroform with LDA is carried out at -110 C to suppress competing formation of dichlorocarbene.6... 

Reaction of diclilorocarbene with substituted benzaldehydes affords the corresponding mandelic acids. It might be supposed that this reaction does not involve dichlorocarben but rather its precursor, the trichloromethide ion. Nucleophilic addition of the trichlorc methyl anion to benzaldehyde should yield phenyl trichloromethyl carbinol. In control experiments, however, phenyl trichloromethyl carbinol was not hydrolyzed to mandelic acid under the reaction conditions. It was suggested that the reaction involves dichlorocarbene addition to the benzaldehyde carbonyl to form 2,2-dichloro-3-phenyloxirane followed by rearrangement to a-chlorophenylacetyl chloride which then is hydrolyzed as shown in equation 3.16. Mandelic, 4-methylmandelic, and 4-methoxymandelic acids were produced in 75%, 80%, and 80% yields, respectively [24]. 

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