Dakin reactions

The Dakin reaction proceeds by a mechanism analogous to that of the Baeyer-Villiger reaction. An aromatic aldehyde or ketone that is activated by a hydroxy group in the ortho or para position, e.g. salicylic aldehyde 12 (2-hydroxybenzaldehyde), reacts with hydroperoxides or alkaline hydrogen peroxide. Upon hydrolysis of the rearrangement product 13 a dihydroxybenzene, e.g. catechol 14, is obtained ... 

In another kind of reaction, an aromatic aldehyde ArCHO or ketone ArCOR is converted to a phenol ArOH on treatment with alkaline H202,226 but there must be an OH or NH2 group in the ortho or para position. This is called the Dakin reaction.12 The mechanism may be similar to that of the Baeyer-Villiger reaction (8-20) 228... 

Alkaline hydrolysis of benzal acetone structures to the corresponding aldehyde (XIX) and acetone and subsequent oxidation of the aldehyde (XIX) to the corresponding benzoic acid (V) do not seem to represent an actual degradation stage since oxidizing the aldehyde (XIX) under our mild standard conditions yielded only traces of the corresponding benzoic acid (V). The aldehyde (XIX) was rapidly decomposed via Dakin reaction to formic acid and 3-methoxy-S-methyl-o-benzoquinone, which is immediately degraded to phenolic humic compounds. 

The Dakin Reaction allows the preparation of phenols from aryl aldehydes or aryl ketones via oxidation with hydrogen peroxide in the presence of base. The aryl formate or alkanoate formed as an intermediate is subsequently saponified to yield the substituted phenol product. 

The compounds studied were 2-methoxyhydroquinone A, 4-methylcatechol B, 2-hydroxy-2,3,3,-trimethoxy-5,5 -di-n-propylbiphenyl C, methoxy-p-benzoquinone D, 4,4 -dimethoxybiphenyl-2,5,2,5,-bisquinone E, 8-hydroxy-3,7-dimethoxydi-benzofuran-l,4-quinone F, 2,5-dihydroxy-2, 3,3 -trimethoxy-5 -hydroxymethyl-biphenyl G, and the related p-quinone H (scheme 1). Compounds A, D, E, and F were synthesized according to ref. [9], and compound Q, was prepared from 2-hydroxy-2,3,3,-trimethoxy-5-formyl-5,-hydroxymethyldiphenyl by Dakin reaction using the same procedure as for compound A. Compound G was isolated in presence of the corresponding p-quinone H. Titration of H was performed by... 

Aldehydes which contain electron-releasing substituents in the ortho or para position give phenol products via a formate intermediate. This reaction is known as the Dakin reaction, the oxidation of salicylaldehyde being a classic example (Figure 3.42).215... 

Figure 3.42 Dakin reaction of aromatic aldehydes to phenols in the presence of alkaline hydrogen peroxide.

Although alkaline conditions are normally employed, for reasons of safety it is occasionally advantageous to operate under neutral conditions where, for example, oxidation of benzaldehydes to benzoic acids may be desired rather than the Dakin reaction.210 Conversely alkyl benzaldehydes, which under most conditions would be expected to yield the corresponding benzoic acids, have been reported to undergo the Dakin-type reaction yielding alkyl phenols in the presence of strong acids.220... 

NaH, dimethylformamide (DMF), CH3I], undergoes electrophilic nitration (89), Friedel-Crafts acylation (90), and alkylation (91) at the C-9 position. Although attempts to effeet a Baeyer-Villiger oxidation of ketone 90 were successful, the route was laborious since oxidation to amine oxide 92 preceded oxidation of the methyl ketone 90. However, a Dakin reaction of aldehyde 91 gave 9-hydroxy-6-methylellipticine (93) in excellent yield. It remains to be seen if this methodology can be extended to an N-unsubstituted ellipticine. 

There are a number of less frequently used methods for the preparation of phenols that are worthy of mention. The rearrangement of 2-hydroxy-benzaldehydes brought about by reaction with alkaline hydrogen peroxide and leading to dihydroxybenzenes (the Dakin reaction ) is discussed in Section 4.8. The acid-catalysed rearrangement of phenylhydroxy-lamines, known as the Bamberger rearrangement, is useful for the synthesis of 4-aminophenols (Scheme 4.3). 

Dihydroxybenzene may be prepared from 2-hydroxybenzaldehyde by the Dakin reaction, which involves oxidation in alkaline solution by hydrogen peroxide (Scheme 4.15). The reaction involves a 1,2-shift to an electron-deficient oxygen and is similar to the cumene process used to synthesize phenol (Section 4.2). 

The oxidative rearrangement of various acylbenzenes with alkaline hydrogen peroxide (the Dakin reaction) can provide a mild method for the synthesis of phenols (Scheme 4.15). 

The intermediate 27 has been isolated." The reaction has been performed on aromatic aldehydes with an alkoxy group in the ring, and no OH or NH2. In this case, acidic H2O2 was used." The Dakin reaction has been done in ionic liquids. 

The most important applications of peroxyacetic acid are the epoxi-dation [250, 251, 252, 254, 257, 258] and anti hydroxylation of double bonds [241, 252, the Dakin reaction of aldehydes [259, the Baeyer-Villiger reaction of ketones [148, 254, 258, 260, 261, 262] the oxidation of primary amines to nitroso [iJi] or nitrocompounds [253], of tertiary amines to amine oxides [i58, 263], of sulfides to sulfoxides and sulfones [264, 265], and of iodo compounds to iodoso or iodoxy compounds [266, 267] the degradation of alkynes [268] and diketones [269, 270, 271] to carboxylic acids and the oxidative opening of aromatic rings to aromatic dicarboxylic acids [256, 272, 271, 272,273, 274]. Occasionally, peroxyacetic acid is used for the dehydrogenation [275] and oxidation of aromatic compounds to quinones [249], of alcohols to ketones [276], of aldehyde acetals to carboxylic acids [277], and of lactams to imides [225,255]. The last two reactions are carried out in the presence of manganese salts. The oxidation of alcohols to ketones is catalyzed by chromium trioxide, and the role of peroxyacetic acid is to reoxidize the trivalent chromium [276]. 

The mechanism is the same as that of the Dakin reaction of aromatic aldehydes (equation 359). The reaction is acid-catalyzed. The peroxy acid transfers oxygen onto the carbon of the carbonyl group and generates an unstable intermediate. A rearrangement of the groups bonded to the original carbonyl carbon results in the formation of esters or, with cyclic ketones, lactones [262, 303] (equation 379). 

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