Ortho-acyl phenols

V. Snieckus and co-workers developed a new carbamoyl Baker-Venkataraman rearrangement, which allowed a general synthesis of substituted 4-hydroxycoumarins in moderate to good overall yields. The intermediate arylketones were efficiently prepared from arylcarbamates via directed ortho metallation and Negishi cross coupling. The overall sequence provided a regiospecific anionic Friedel-Crafts complement for the construction of ortho-acyl phenols and coumarins. 

The Fries rearrangement proceeds via ionic intermediates but the exact mechanistic pathway (whether it is inter- or intramolecular) is still under debate. There are many reports in the literature that present evidence to support either of the pathways, but it appears that the exact route depends on the structure of the substrates and the reaction conditions. The scheme depicts the formation of an ortho-acylated phenol from a substituted phenolic ester in the presence of aluminum trihalide catalyst. The photo-Fries rearrangement proceeds via radical intermediates. ... 

Research in the laboratory of P. Magnus showed that the macrocyclic skeleton of diazonamide could be synthesized with the use of macroiactonization followed by a photo-Fries rearrangement. First, the aromatic carboxylic acid and the phenol were coupled with EDCI to form the macrolactone (phenolic ester), which was then exposed to light at high-dilution to cleanly afford the macrocyclic ortho-acylated phenol skeleton of diazonamide. 

Hoesch reaction. In most cases, a Lewis acid is necessary zinc chloride is the most common. The reaction is generally useful only with phenols, phenolic ethers, and some reactive heterocyclic compounds (e.g., pyrrole), but it can be extended to aromatic amines by the use of BCls. Acylation in the case of amines is regioselectively ortho. Monohydric phenols, however, generally do not give ketones " but are attacked at the oxygen to produce imino esters. Many nitriles... 

The Hf(OTf)4, is also effective in the ortho-acylation of phenols using carboxylic acids instead of the acid chlorides, although somewhat lower yields are obtained and larger amounts of the catalyst are required (equations 42 and 43). ... 

Fig. 4 Structure of ortho-acyl-/V-phenol amine MC1863...

The metal-template effect is also exploited as a powerful instrument to achieve highly selective ortho-acylation of the phenol ring in the... 

Unusual Friedel-Crafts reactions, IX. One-step ortho-acylation of phenols with a,(3-unsaturated acyl chlorides. Synthesis of 2 -hydroxychalcones and sorbicillin analogues. Tetrahedron 40 4081-4084. 

Sartori, G., Casnati, G., Bigi, R, and Bonini, G. 1988. Metal template ortho acylation of phenols direct synthesis of salicylic acid chlorides and derivatives. Synthesis 763-766. 

The reaction may produce both ortho and para acylated phenols, the former generally favored by high temperatures and the latter by low temperatures, (a) Suggest an experiment that might indicate whether the reaction is inter- or intramolecular, (b) Explain the temperature effect on product formation. 

Carboxylates Among various 0-substituted electrophiles, O-acylated phenols share a few distinct advantages over other pseudohahdes (i) they are readily available and affordable, (ii) they are relatively stable substrates to various reaction conditions, and (iii) they can serve as directing groups for aromatic substitution reactions such as directed ortho-metallations (DoMs) [58]. Moreover, these carboxylates are much more environmentally friendly, generating acetate salts as the only by-product in the Suzuki-Miyaura cross-coupling reaction [59,... 

Scheme 8.121 Synthesis of xanthone derivatives via ortho-acylation of phenols with aryl aldehydes.

HOUBEN - HOESCH Phenol Acylation Synthesis ol ketones (or aldehydes) by acylation ol phenols with nitriles (or ortho formates)... 

Synthesis of the remaining half of the molecule starts with the formation of the monomethyl ether (9) from orcinol (8). The carbon atom that is to serve as the bridge is introduced as an aldehyde by formylation with zinc cyanide and hydrochloric acid (10). The phenol is then protected as the acetate. Successive oxidation and treatment with thionyl chloride affords the protected acid chloride (11). Acylation of the free phenol group in 7 by means of 11 affords the ester, 12. The ester is then rearranged by an ortho-Fries reaction (catalyzed by either titanium... 

Note Color reactions occur even before application of spray solution II [6]. Tertiary aliphatic amines and phenols with blocked ortho and para positions and aromatic N-acylated amines, e.g. acetanilide, do not react [1],... 

Tyrosine may be targeted specifically for modification through its phenolate anion by acylation, through electrophilic reactions such as the addition of iodine or diazonium ions, and by Mannich condensation reactions. The electrophilic substitution reactions on tyrosine s ring all occur at the ortho position to the —OH group (Figure 1.11). Most of these reactions proceed effectively only when tyrosine s ring is ionized to the phenolate anion form. 

Fries rearrangement.1 Rearrangement of phenyl esters with Lewis acids results in a mixture of ortho- and para-phenolic ketones. In contrast, reaction of an o-bromophenyl ester with sec-butyllithium results in exclusive formation of the orf/jo-phenolic ketone by an intramolecular acyl rearrangement.2... 

Phenol esters of a,(3-unsaturated carboxylic acids have an interesting reactivity due to the synthetic utility of the resulting hydroxychalcones (Scheme 19). This aspect will be illustrated in Section IV. However, from the basic point of view, it is worth mentioning that the cis or trans configuration of the olefinic part of the acyl moiety can have a marked influence on the photochemical reactivity of the ester. When para-methoxyphenyl fumarates are irradiated, the normal ortho-rearranged products are obtained. By contrast, irradiation of para-me-thoxyphenyl maleates does not lead to rearrangement. Instead, cyclization products are obtained (Scheme 20). 

The consecutive formation of o-hydroxybenzophenone (Figure 3) occurred by Fries transposition over phenylbenzoate. In the Fries reaction catalyzed by Lewis-type systems, aimed at the synthesis of hydroxyarylketones starting from aryl esters, the mechanism can be either (i) intermolecular, in which the benzoyl cation acylates phenylbenzoate with formation of benzoylphenylbenzoate, while the Ph-O-AfCL complex generates phenol (in this case, hydroxybenzophenone is a consecutive product of phenylbenzoate transformation), or (ii) intramolecular, in which phenylbenzoate directly transforms into hydroxybenzophenone, or (iii) again intermolecular, in which however the benzoyl cation acylates the Ph-O-AfCL complex, with formation of another complex which then decomposes to yield hydroxybenzophenone (mechanism of monomolecular deacylation-acylation). Mechanisms (i) and (iii) lead preferentially to the formation of p-hydroxybenzophenone (especially at low temperature), while mechanism (ii) to the ortho isomer. In the case of the Bronsted-type catalysis with zeolites, shape-selectivity effects may favor the formation of the para isomer with respect to the ortho one (11,12). 

In our case, all the compounds obtained by transformation of the intermediate, phenylbenzoate, were primary products. This indicates that the following parallel reactions occurred on phenylbenzoate (1) the intramolecular Fries transposition generated o-hydroxybenzophenone, (ii) phenylbenzoate acted as a benzoylating agent on phenol, to yield p-hydroxybenzophenone (with also possible formation of the ortho isomer) and phenol and (iii) phenylbenzoate acylated a second molecule of phenylbenzoate to generate benzoylphenylbenzoates, with the co-production of phenol. 

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