✍ Scribed by Norbert De Kimpe; Christian Stevens
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The oxidation of aldehydes to a@-unsaturated aldehydes has been performed by a sequence of reactions involving conversion into aldimines, chlorination at the a-position to form a-chloroaldimines, base-induced dehydrochlorination and h drol sis The four-step transformation can be executed without isolation of the intermediates. This metKod xas'been applied to the synthesis of an artificial flavor, i.e. 2-butyl-3phenylpropenal. a,/?-Unsaturated aldehydes are important functionalyzed carbonyl compounds in synthetic organic chemistry. They have a pronounced industrial use as synthetic flavor additive of candies, baked goods, ice-cream and dairy productsio2. In addition, a,/?-unsaturated aldehydes contribute to some extent to the natural flavor of vegetables, e.g. onions'. Branched 2-alkenals are formed during frying or roasting of foods and contribute as such significantly to the flavor characteristics of foodstuffs. Most a,p-unsaturated aldehydes are synthesized via a variety of condensation reactions. There exist relatively few methods for aldehydes and subsequent dehydrohalogenation is not a successful procedure because of competing side reactions in the latter step12. A better method consists of converting a-bromoaldehydes into the corresponding N,N-dimethylhydrazones, which are in situ dehydrobrominated and hydrolyzed to a,/?-unsaturated aldehydes . Drawbacks of this procedure are the rather low yields of the a-bromination and the long continuous extraction procedure for the ad-unsaturated aldehyde after hydrolysis4. An improved method utilized a sequence of reactions in which an aldehyde is converted into a piperidine enamine, and then phenylselenenylated and hydrolyzed to an a-(phenylse1eno)aldehyde; oxidation of the latter (mCPBA or Na104) gives a,/?-unsaturated aldehydes5.
We now describe an alternative method for the conversion of aldehydes to conjugated enals via a-chloroaldimines. The aldehydes 1 were transformed with primary amines to aldimines 2, which were cleanly chlorinated at the a-position using N-chlorosuccinimide in carbon tetrachloride. Dehydrochlorination of the a-chloroaldimines 3 with sodium methoxide in refluxing methanol provided a,/?-unsaturated aldimines 3, which were hydrolyzed with aqueous oxalic acid in the two-phase-system dichloromethane-water to afford a,/?-unsaturated aldehydes 5. The enals, thus obtained, were free from side products and can be used for subsequent reactions without further purification. N-lsopropylimines are suitable substrates for the transformations described above but loss of product occurs during evaporation of the solvents. This can be circumvented by using N-cyclohexylimines. It is not necessary to purify the intermediates of this synthetic scheme; for instance cyclohexanecarboxaldehyde 1 (R -R = (CH2)4) was transformed into 1-cyclohexene-I-carboxaldehyde & (R -R = (CH2)4) in 74 %overall yield after a final distillation (Table ).
Aldehydes bearing no a-alkyl substituents (i.e. 1 : R2 = H) cannot be transformed conveniently via this route into a,/?-unsaturated aldehydes because the monochlorination of the appropriate aldimines is problematic. Indeed, as a general rule, the chlorination of imines carrying an a-CH2, with one molar equivalent of performing the conversion of aldehydes (e.g.1) to a,/?-unsaturated aldehydes (e.g. 5
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