Phenols reactions with carboxylic acid

The reaction with carboxylic acid and acid anhydride is carried out in the presence of a small amount of concentrated sulphuric acid. The reaction is reversible, and therefore, water is removed as soon as it is formed. The reaction with acid chloride is carried out in the presence of a base (pyridine) so as to neutralise HCl which is formed during the reaction. It shifts the equilibrium to the right hand side. The introduction of acetyl (CH3CO) group in alcohols or phenols is known as acetylation. Acetylation of salicylic acid produces aspirin. 

Trimethylsilyl ethers and esters.i The reaction of alcohols and allyltrimethyl-silane in acetonitrile with TsOH as catalyst (70 80°, 1 3 hours) results in trimethyl-silyl ethers in 85-95% yield with elimination of propene. The same reaction with carboxylic acids results in trimclhylsilyl esters. Phenols do not undergo this reaction. 

Reaction of 3-acetylcoumarins with Vilsmeier reagents has given propeniminium salts (154) which are useful intermediates.165 4-Diazomethyl-7-methoxycoumarin is unexpectedly stable and does not react with alcohols or phenols but with carboxylic acids, it yields... 

The sites of alkylation are the oxygen atoms of the hydroxyl, carbonyl, and carboxyl groups in lignin. Reactions a and b are selective with diazoalkanes (a) reacting under anhydrous conditions to alkylate, chiefly, the slightly acidic hydroxyl groups (98) of the phenolic, enolic(99-102), and carboxylic (103-107) units to form ethers. The diazoalkane reaction with carboxylic acids only occurs in solvents in which the acid is deprotonated to an enolate anion. The RN reactions are shown in Equation 2. 

Phenols react with carboxylic acid anhydrides and acid chlorides to form esters. These reactions are quite similar to those of alcohols (Section 17.7). 

Phenolic compounds are weaker nucleophiles and better leaving groups than aliphatic alcohols. They do not yield polyesters when reacted with carboxylic acids or alkyl carboxy lates. The synthesis of polyesters from diphenols is, therefore, generally carried out through the high-temperature carboxylic acid-aryl acetate or phenyl ester-phenol interchange reactions with efficient removal of reaction by-product (Schemes 2.10 and 2.11, respectively). 

Finally, a new water-soluble polyphosphazene was recently synthesized that has the structure shown in 36 (46). This polymer has two attributes as a biomedical macromolecule. First, the pendent carboxylic acid groups are potential sites for condensation reactions with amines, alcohols, phenols, or other carboxylic acid units to generate amide, ester, or anhydride links to polypeptides or bioactive small molecules. Second, polymer forms ionic crosslinks when brought into contact with di- or trivalent cations such as Ca or Ai3+. The crosslinking process converts the water-soluble polymer to a hydrogel, a process that can be reversed when the system... 

MnP is the most commonly widespread of the class II peroxidases [72, 73], It catalyzes a PLC -dependent oxidation of Mn2+ to Mn3+. The catalytic cycle is initiated by binding of H2O2 or an organic peroxide to the native ferric enzyme and formation of an iron-peroxide complex the Mn3+ ions finally produced after subsequent electron transfers are stabilized via chelation with organic acids like oxalate, malonate, malate, tartrate or lactate [74], The chelates of Mn3+ with carboxylic acids cause one-electron oxidation of various substrates thus, chelates and carboxylic acids can react with each other to form alkyl radicals, which after several reactions result in the production of other radicals. These final radicals are the source of autocataly tic ally produced peroxides and are used by MnP in the absence of H2O2. The versatile oxidative capacity of MnP is apparently due to the chelated Mn3+ ions, which act as diffusible redox-mediator and attacking, non-specifically, phenolic compounds such as biopolymers, milled wood, humic substances and several xenobiotics [72, 75, 76]. 

The starting material is an 18 electron nickel zero complex which is protonated forming a divalent nickel hydride. This can react further with alkenes to give alkyl groups, but it also reacts as an acid with hard bases to regenerate the nickel zero complex. Similar oxidative addition reactions have been recorded for phenols, water, amines, carboxylic acids, mineral acids (HCN), etc. 

Methylation. The reaction with diazomethane has often been used for differentiating the acidic groups (28, 35, 38, 45, 46, 69). Diazomethane reacts, in general, with carboxylic acids, forming methyl esters which are easily hydrolyzed by dilute hydrochloric acid. With phenols, ethers are formed which are stable to hydrolysis. Alcohols are methylated only if catalysts are present, e.g., BF, ZnClj (70), or HjO (71). As Garten et al. 

SYNTHESIS and CHARACTERIZATION of O-ALKYLATED EXTRACTS. Alkylation occurs when tetrabutylanunonium hydroxide is used to promote the reaction of the alkyl iodide with the coal in tetrahydrofuran.(14) The alkylation reaction occurs primarily on acidic oxygen functionalities such as phenolic hydroxyl and carboxylic acid groups, as shown below. 

The Pechmann and Knoevenagel reactions have been widely used to synthesise coumarins and developments in both have been reported. Activated phenols react rapidly with ethyl acetoacetate, propenoic acid and propynoic acid under microwave irradiation using cation-exchange resins as catalyst <99SL608>. Similarly, salicylaldehydes are converted into coumarin-3-carboxylic acids when the reaction with malonic acid is catalysed by the montmorillonite KSF <99JOC1033>. In both cases the use of a solid catalyst has environmentally friendly benefits. Methyl 3-(3-coumarinyl)propenoate 44, prepared from dimethyl glutaconate and salicylaldehyde, is a stable electron deficient diene which reacts with enamines to form benzo[c]coumarins. An inverse electron demand Diels-Alder reaction is followed by elimination of a secondary amine and aromatisation (Scheme 26) <99SL477>. 

It is possible to prepare esters of phenols with carboxylic acid anhydrides or acid halides, and phenyl ethers by reaction of benzenolate anion with halides, sulfate esters, sulfonates, or other alkyl derivatives that react well by the SN2 mechanism ... 

The reaction of a hydroperoxide with 2-methylaziddine [75-55-8] has been described (94). The reaction of ethyleneimine with phenols (95) and carboxylic acids (96,97) produces ethylamine ethers and esters, respectively. However, these reactions frequendy yield product mixtures which contain polyaminoalkylated oxygen nucleophiles and polymers, in addition to the desired products (1). The selectivity of the reaction can often be improved by using less than the stoichiometric amount of the azitidine component (98,99). 

General methylation procedure with diazomethane. The reaction must be carried out in the fume cupboard. Dissolve 2-3 g of the compound (say, a phenol or a carboxylic acid) in a little anhydrous ether or absolute methanol, cool in ice and add the ethereal solution of diazomethane in small portions until gas evolution ceases and the solution acquires a pale yellow colour. Test the coloured solution for the presence of excess of diazomethane by removing a few drops into a test tube and introducing a glass rod moistened with glacial acetic acid immediate evolution of gas should occur. Evaporate the solvent, and purify the product by distillation or crystallisation. 

Merker, R. L. Scott, M. J. The reaction of alkyl halides with carboxylic acids and phenols in the presence of tertiary amines./. Org. Chem. 1961, 26, 5180-5182. 

Fries rearrangement and phenol acetylation The Fries rearrangement is the acid catalysed transformation of aryl esters into hydroxyarylketones. Both this rearrangement and the two-step transformation (esterification, Fries rearrangement) in one-pot operation of phenols with carboxylic acid or anhydrides will be examined hereafter. Most studies in which acid zeolites were used as catalysts (Tables 3.6 and 3.7) deal with the synthesis of o- and p-hydroxyacetophenones (o- and p-HAP) either by the Fries rearrangement of phenyl acetate [Reaction (3.5)] ... 

Step-Growth Polymerization. Only a relative few of the dozens of active hydrogen compounds that undergo reactions with the epoxy ring find widespread use in epoxy structural adhesives. The most common are amines, acid anhydrides, phenols, thiols, and carboxylic acids. 

Nitrobenzoxazoles possessing nonlinear optical properties [451], like their nonnitrated analogs, are easily obtained in the reaction of the corresponding ortho-samno-phenols with carboxylic acids [452-458], aldehydes [459, 460], or chloroanhydrides [134, 461—464] (Scheme 2.70). 

Aryl esters. Esters can be obtained in 50-90% yield from phenols and aromatic carboxylic acids by reaction with PPE in DMF al 20-85° for 3-150 hours, Stcrically... 

BenzeylatUnn. Reaction of 1 with carboxylic acids, amines, and phenols produces mixed anhydrides, benzamides, and benzoate esters, respectively, in good yield. These reactions can also be carried out using C6H5COCI and 0.3 equiv. of 2 in place of preformed 1. ... 

Further, the use of commercially available PS-PPha resin combined with microwave condition to lead to a variety of benzoxazoles (xLv) in high purities and yields was given by Wang et al. [71]. The protocol involved a one-step reaction of carboxylic acid with 2-amino phenols. 

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