Dakin reaction mechanism

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... 

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). 

Dakin reaction. This reaction also employs hydrogen peroxide in a basic medium. It is applicable to a phenol carrying in the ortho position either an aldehydic or a ketonic group. Thus salicylaldehyde is converted by alkaline hydrogen peroxide into catechol in good yield." The reaction has been interpreted by the mechanism formulated. 

Although the mechanism of the Dakin reaction given in many textbooks does not involve participation of the n electron of the aromatic ring, the mandatory presence of polar substituents (e.g., OH) in the ortho or para position to the formyl group suggests that an internal electrophilic substitution of the adduct intermediate is a better representation. The uncatalyzed S Ar process is a soft-soft interaction. 

The oxidation of aromatic aldehydes could be complicated. In addition to direct oxidation to the dicarboxylic acid (phthalic acid), an aromatic aldehyde carbonyl could also be oxidized and then rearranged and hydrated to form a phenol via aryl formates (Dakin reaction)." Thus, when treating p-hydroxy-benzaldehyde, 25, with basic hydrogen peroxide, the following mechanism is actually involved (Fig. 10). 

Baeyer-Villiger or Dakin reaction for the conversion of phenyl ketones to phenyl esters [60, 61]. The concerted atom migration reaction in Fig. lb proceeds by a fundamentally different mechanism than the displacement reaction shown in Fig. la. In this case, the C-O bond formation proceeds by attack of the nucleophilic carbon of [(HOO)(R )C(0)-R ] on an electrophilic O-atom of HOO that is generated by loss of OH. Here, the EDG group on the nucleophilic carbon is the negatively charged [(H00)(R)C(0)]] fragment. 

When an a-amino acid is treated with an anhydride in the presence of pyridine, the carboxyl group is replaced by an acyl group and the NH2 becomes acylated. This is called the Dakin-West reaction The mechanism involves formation of an oxazolone. The reaction sometimes takes place on carboxylic acids even when an amino group is not present. A number of N-substituted amino acids, RCH-(NHR )COOH, give the corresponding N-alkylated products. 

Under Dakin-West reaction conditions (trifluoroacetic anhydride-MeCN/80 °C/5 h), At-methoxycarbonylproline (128 R = Me) yielded Af-methoxycarbonyl-4-trifluoro-acetyl-2,3-dihydropyrrole (129 R = Me) and none of the expected Dakin-West product, the trifluoromethyl ketone (127). A possible mechanism proposed by the authors involves initial formation of a mesoionic l,3-oxazolium-5-olate (130 R = Me), but the pathway to the iV-methoxycarbonyl-2,3-dihydropyrrole (131 R = Me) and thence the final product (129 R = Me) was unexplained. ... 

The base-catalyzed Michael addition of oxazolin-5-ones to alkynic ketones produces 4-(3-oxopropenyl) derivatives (405) (79CB3221). The latter compounds are cleaved on warming with oxalic acid dihydrate in acetic acid to y-diketones (406). The mechanism of this transformation corresponds to a vinylogous Dakin-West reaction (Scheme 90). 

Treatment of an a-amino acid with an anhydride in the presence of pyridine, known as the Dakin-West reaction,[1431 gives access to a racemic a-amido ketone.1 44 1451 The mechanism involves formation of an oxazolinone (98)J146 In the modified Dakin-West reaction, the oxazolinone is reacted with an acid chloride (Scheme 33)J136 139] Due to the rapid epimer-ization of the oxazolinones, a diastereomeric mixture of product 99 is obtained. No detailed protocol has been published so far for the modified Dakin-West synthesis applied to (oxomethyleneamino) peptides, but the procedure is adapted from that already reported for (oxomethylene) peptides containing the tp[CO-CH2] link.1147 ... 

All three isomerizations discussed above seem to occur by analogous mechanistic pathways similar to the mechanism formulated for the Dakin-West reaction [82]. Deacylation of the starting material H by catalyst G affords, in a fast and reversible step (Scheme 13.47, step I), an acylpyridinium/enolate ion-pair I. From this ion pair, enantioselective C-acylation proceeds in the rate-determining and irreversible second step, furnishing the C-acylated product J (Scheme 13.47, step II). 

Otvos, L., Marton, J., Meisel-Agoston, J. Investigations with radioactive acetic anhydride. I. On the mechanism of the Dakin-West reaction. II. The mechanism of the reaction between aromatic isocyanates and acid anhydrides. Acta Chim. Acad. Sci. Hung. 1960, 24, 327-331. Otvos, L., Marton, J., Meisel-Agoston, J. Investigations with radioactive acetic anhydride. I. On the mechanism of the Dakin-West reaction. Acta Chim. Acad. Sci. Hung. 1960, 24, 321-325. 

Singh, G., Singh, S. Synthesis of a new mesoionic aromatic system and the mechanism of the Dakin-West reaction. Tetrahedron Lett. 

Knorr, R., Huisgen, R. Mechanism of the Dakin-West reaction. I. Reaction of secondary N-acylamino acids with acetic anhydride. Chem. Ber. 1970,103, 2598-2610. 

Knorr, R Staudinger, G. K. Mechanism of the Dakin-West reaction. II. Kinetics and mechanisms of the Dakin-West reaction of N-acylated secondary amino acids. Chem. Ber. 1971,104, 3621-3632. 

R2 = CH3 or C2H5). In addition, 511a and 511b have been isolated from reaction of 510a and 510b with TFAA. These intermediates are consistent with the mechanism of a Dakin-West reaction. 

A suggested mechanism, which is related to the Dakin-West reaction, is shown in Scheme 4.5. Evidence in support of this mechanism is seen with the isolation of 64 and 65 with bulky R groups, the latter structure of which was supported by X-ray crystallography (Fig. 4.19). 

A Dakin-West reaction on plant scale is demonstrated by elaboration of a modified procedure avoiding uncontrolled release of carbon dioxide. It seems to be generally accepted that the mechanism involves dehydrative formation of an azlactone (oxazolinone), which is then C-acylated (in equilibria with G-acylation), undergoes ring-opening hydrolysis, and then decarboxylates to form the acylamino ketone. Pyrimidine ring formation is achieved in a simple one-pot reaction, which is followed by a simple isomerization. Laboratory experiments had made clear that the mechanism... 

In case of Al-acylprolines 19, the key intermediate of reaction (A) was isolated. A similar mechanism has been postnlated in the Dakin-West reaction. The cleavage of N-C bond of the intermediate (B) readily occnrs upon the attack of the trifluoro-acetate anion becanse of the hindered 5-5 bicyclic system. 

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