Dakin-like reaction

Finally, 1-a-bond cleavage is illustrated by the so-called Dakin-like reaction (P, Fig. 1.5) (Kratzl et al. 1974). In this reaction the side chain is displaced from a phenolic ring through attack by molecular oxygen under alkaline conditions. 

Dakin and Dakin-like Reactions Cinnamaldehydes or aromatic structures containing carbonyl substituents para to a free phenolic hydroxyl group (e.g., p-hydroxy-acetophenones) react with stabilized alkaline peroxide to form benzaldehydes and hydroquinones, respectively [37,38], Structures containing aryl-a-carbonyl substituents para to an etherilied phenolic group are degraded more slowly [39]. 

Fluoromethyl ketones are one of the most widely used classes of peptidyl a-fluoroalkyl ketones, second only to trifluoromethyl ketones. Peptidyl fluoromethyl ketones are very effective as irreversible inhibitors of cysteine proteases the first reported use of a fluoromethyl ketone compound was the use of Z-Phe-Ala-CH2F as an irreversible inhibitor of cathepsin BJ2,31 Today, many lysine and arginine derivatives have been synthesized as potential inhibitors for trypsin and trypsin-like enzymesJ3 There are four basic methods for the synthesis of peptide fluoromethyl ketones (1) the reaction of HF with peptide diazomethyl ketones (Section 15.1.4.1.1), (2) a halogen-exchange reaction with a chloro-, bromo-, or iodomethyl ketone (Section 15.1.4.1.2), (3) a Henry nitro-aldol condensation reaction (Section 15.1.4.1.3), and (4) a modified Dakin-West acylation reaction (Section 15.1.4.1.4). 

What product will actually form Will catechol form via the Dakin reaction Aromatic aldehydes in Dakin reactions usually need to have an electron-donating group, like hydroxyl, alkoxyl or amino groups, in the ortho- or para- positions. This is illustrated in a few more examples shown below (Fig. 12). ... 

The green colour reaction with ferric salts indicated the presence of a catechol, or o-dihydroxy benzene nucleus, and this was confirmed by the production of protocatechuic acid (3 4-dihydroxy benzoic acid) on fusion of adrenaline wdth KOH. Von Ffirth showed that a methylamino and a secondary alcohol group were present in the form of a side-chain, —CH(OH).CH2.NH.CHg, from which the carboxyl group of the protocatechuic acid was derived. Thus, the formula of adrenaline is 3 4-dihydroxyphenyl-ethanohnethylamine, and it is related both to tyrosine and to the tyrosine metabolite, dihydroxyphenyl alanine (dopa). Adrenaline has been synthesised independently by Stolz (1904) and by Dakin, starting from catechol. Like the other dihydroxy phenols, adrenaline is unstable in alkaline solution, and readily oxidised to a red pigment. 

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