Course Name - ORGANIC CHEMISTRY- II BSc. B.Ed VIII th Semester Course Code-CHE-351 By Dr. Mahender Khatravath Central University of south Bihar, Gaya Outline

 Friedel craft acylation

 Acylation Of Phenols

 Carboxylation Of Phenols: Aspirin And The Kolbe–schmitt Reaction

 Mechanism of Fries rearrangement

 Claisen rearrangement

 Reimer-Tiemann Reaction Mechanism for Friedel craft acylation

 Acylating agents, such as acyl chlorides and carboxylic acid anhydrides, can react with phenols either at the aromatic ring (C-acylation) or at the hydroxyl oxygen (O-acylation): Acylation Of Phenols  C-acylation of phenols is observed under the customary conditions of the Friedel–Crafts reaction (treatment with an acyl chloride or acid anhydride in the presence of aluminum chloride). In the absence of aluminum chloride, however, O-acylation occurs instead.

 The O-acylation of phenols with carboxylic acid anhydrides can be conveniently catalyzed in either of two ways. One method involves converting the acid anhydride to a more powerful acylating agent by protonation of one of its carbonyl oxygens. Addition of a few drops of sulfuric acid is usually sufficient.

Carboxylation Of Phenols: Aspirin And The Kolbe–schmitt Reaction

 The best known aryl ester is O-acetylsalicylic acid, better known as aspirin. It is prepared by acetylation of the phenolic hydroxyl group of salicylic acid

 The key compound in the synthesis of aspirin, salicylic acid, is prepared from phenol by a process discovered in the nineteenth century by the German chemist Hermann Kolbe. In the Kolbe synthesis, also known as the Kolbe–Schmitt reaction, sodium phenoxide is heated with carbon dioxide under pressure, and the reaction mixture is subsequently Acidified to yield salicylic acid. Kolbe–schmitt Reaction Mechanism  Hydroxyl group strongly activates an aromatic ring toward electrophilic attack, an oxyanion substituent is an even more powerful activator. Electron delocalization in phenoxide anion leads to increased electron density at the positions ortho and para to oxygen.  The Kolbe–Schmitt reaction is an equilibrium process governed by thermodynamic control. The position of equilibrium favors formation of the weaker base (salicylate io n) at the expense of the stronger one (phenoxide ion). Thermodynamic control is also responsible for the pronounced bias toward ortho over para substitution. Salicylate anion is a weaker base than p-hydroxybenzoate and so is the predominant species at equilibrium. Mechanism of Fries rearrangement  conversion of phenolic esters to the corresponding ortho and/or para substituted phenolic ketones and aldehydes, in the presence of Lewis or Brönsted acids is called the Fries rearrangement . The Fries rearrangement has the following general features:  Usually it is carried out by heating the phenolic ester to high temperatures (80-180 °C) in the presence of at least one equivalent of Lewis acid or Brönsted acid (e.g., HF, HClO4 , PPA).  The reaction time can vary between a few minutes and several hours; 3) Lewis acids that catalyze the Friedel-Crafts acylation are all active but recently solid acid catalysts (e.g., zeolites, mesoporous molecular sieves) and metal triflates have also been used.  The rearrangement is general for a wide range of structural variation in both the acid and phenol component of phenolic esters.  Yields are the highest when there are electron-donating substituents on the phenol, while electron withdrawing substituents result in very low yields or no reaction;  With polyalkylated phenols alkyl migration is often observed under the reaction conditions;  The Friedel-Crafts acylation of Phenols is usually a two-step process. Formation of a phenolic ester followed by a Fries rearrangement.  The selectivity of the rearrangement to give ortho or para-substituted products largely depends on the reaction conditions (temperature, type, and amount of catalyst, solvent polarity, etc.).  At high temperatures without any solvent the ortho-acylated product dominates while low temperatures favor the formation of the para-acylated product.  With increasing solvent polarity the ratio of the para-acylated product increases; and 11) optically active phenolic esters rearrange to optically active phenolic ketones. Mechanism of Fries rearrangement  conversion of phenolic esters to the corresponding ortho and/or para substituted phenolic ketones and aldehydes, in the presence of Lewis or Brönsted acids is called the Fries rearrangement .

Claisen rearrangement

The thermal [3,3]-sigmatropic rearrangement of allyl vinyl ethers to the corresponding -unsaturated carbonyl compounds is called the Claisen rearrangement .

The allyl vinyl ethers can be prepared in several different ways: 1) from allylic alcohols by mercuric ion–catalyzed exchange with ethyl vinyl ether; 2) from allylic alcohols and vinyl ethers by acid catalyzed exchange. 3) thermal elimination; 4) Wittig olefination of allyl formates and carbonyl compounds. and 5) Tebbe olefination of unsaturated esters; It is usually not necessary to isolate the allyl vinyl ethers, since they are prepared under conditions that will induce their rearrangement.

Reimer-Tiemann Reaction

 In 1876, K. Reimer and F. Tiemann discovered that the treatment of phenol with chloroform in 10% NaOH solution led to the formation of the corresponding o-hydroxy benzaldehyde as the major product. The formylation of phenols and heterocyclic phenols using chloroform in an aqueous alkaline medium is known as the Reimer-Tiemann reaction . Mechanism of the reaction The general features of the Reimer-Tiemann reaction are:  It is the only electrophilic aromatic substitution reaction that occurs under basic conditions in a protic solvent.  Phenols, naphthols, alkyl-, alkoxy-, and halogenated phenols, salicylic acid derivatives, heterocyclic phenols such as hydroxyquinolines and hydroxypyrimidines, as well as pyrroles and indoles undergo formylation under the reaction conditions.  Typically the substrate (phenol) is dissolved in 10-40% alkali hydroxide, excess chloroform is added, and the biphasic solution is vigorously stirred at elevated temperatures.  Besides CHCl3, other dichlorocarbene precursors such as chloral, trichloronitromethane, etc. can be used.  The regioselectivity is not high, but ortho-formyl products tend to predominate. When the ortho-position is already substituted, para-formyl phenols are obtained.  In the case of pyrroles, when the ortho substituent is a CO2H or CO R group, decarboxylation is observed and the o- formyl product is formed (similar findings were reported for an o-alkoxy phenol where the alkoxy group was eliminated to give an o-formyl phenol);

 When the reaction is conducted in the presence of cyclodextrins, the p-formyl product is formed predominantly.