ORGANIC CHEMISTRY- II Semester Course Code-CHE-351 By Dr ... · In the absence of aluminum chloride, however, O-acylation occurs instead. The O-acylation of phenols with carboxylic

Course Name - ORGANIC CHEMISTRY- II BSc. B.Ed VIIIth Semester

Course Code-CHE-351By

Dr. Mahender KhatravathCentral 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 thearomatic 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-acylationoccurs instead.

The O-acylation of phenols with carboxylic acid anhydrides can be conveniently catalyzed in either of two ways. Onemethod involves converting the acid anhydride to a more powerful acylating agentby protonation of one of its carbonyloxygens. Addition of a few drops of sulfuric acid is usually sufficient.

Carboxylation Of Phenols: Aspirin And The Kolbe–schmitt Re action

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 thenineteenth century by the German chemist Hermann Kolbe. In the Kolbe synthesis, also known as theKolbe–Schmittreaction, sodium phenoxide is heated with carbon dioxide under pressure, and the reaction mixture is subsequentlyAcidified 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 toincreased electron density at the positions orthoand para to oxygen.

The Kolbe–Schmitt reaction is an equilibriumprocess governed by thermodynamic control.The position of equilibrium favors formationof the weaker base (salicylate ion) at theexpense of the stronger one (phenoxide ion).Thermodynamic control is also responsiblefor the pronounced bias toward ortho overpara substitution. Salicylate anion is a weakerbase thanp-hydroxybenzoate and so is thepredominant species at equilibrium.

conversion of phenolic esters to the correspondingortho and/or para substituted phenolic ketones and aldehydes, in thepresence of Lewis or Brönsted acids is called theFries rearrangement.

Mechanism of 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 theFriedel-Crafts

acylation are all active but recently solid acid catalysts (e.g., zeolites, mesoporous molecular sieves) and metaltriflates have also been used.

The rearrangement is general for a wide range of structural variation in both the acid and phenol component ofphenolic esters.

Yields are the highest when there are electron-donating substituents on the phenol, while electron withdrawingsubstituents result in very low yields or no reaction;

With polyalkylated phenols alkyl migration is often observed under the reaction conditions; TheFriedel-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 giveortho 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 theortho-acylated product dominates while low temperatures favor the

formation of thepara-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 ketonesand aldehydes, in the presence of Lewis orBrönsted acids is called theFries rearrangement.

Claisen rearrangementThe 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–catalyzedexchange with ethyl vinyl ether;2) from allylic alcohols and vinyl ethers by acid catalyzed exchange. 3) thermal elimination; 4)Wittig olefination of allylformates and carbonyl compounds. and 5)Tebbe olefination of unsaturated esters; It is usually not necessary to isolate theallyl vinyl ethers, since they are prepared under conditions that will induce theirrearrangement.

Reimer-Tiemann Reaction

In 1876, K. Reimer and F. Tiemann discovered that the treatment of phenol with chloroform in 10% NaOH solution led to theformation of the correspondingo-hydroxy benzaldehyde as the major product. The formylation of phenols and heterocyclicphenols using chloroform in an aqueous alkaline medium is known as theReimer-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, butortho-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 theo-

formyl product is formed (similar findings were reported for ano-alkoxy phenol where the alkoxy group was eliminated to

give an o-formyl phenol);

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