Sulfuric acid Fischer esterification

The mechanism for the acid-catalyzed (sulfuric acid) Fischer esterification reaction below is addition, p.t., p.t., elimination write out the mechanism with all its steps. Remember to choose between the three types of additions, AdE2, AdN2, or AdgS, then choose between the three types of eliminations, El, E2, or ElcB. 

Fischer esterification is the preparation of an ester by treating a carboxylic acid with an alcohol in the presence of an acid catalyst such as sulfuric acid. Fischer esterification is reversible. 

The mechanism for the Fischer esterification is shown in Figure 19.3. Sulfuric acid, hydrochloric acid, orp-toluenesulfonic acid is most often used as a catalyst. The mechanism will be easier to remember if you note the similarities to other acid-catalyzed mechanisms, such as the one for the formation of acetals in Figure 18.5. Also note that the steps leading from the tetrahedral intermediate to the carboxylic acid and alcohol starting materials and to the ester and water products are very similar. 

The mechanism of the Fischer esterification was controversial until 1938, when Irving Roberts and Harold Urey of Columbia University used isotopic labeling to follow the alcohol oxygen atom through the reaction. A catalytic amount of sulfuric acid was added to a mixture of 1 mole of acetic acid and 1 mole of special methanol containing the heavy lsO isotope of oxygen. After a short period, the acid was neutralized to stop the reaction, and the components of the mixture were separated. 

The Fischer esterification, named after the eminent German chemist Emil Fischer, is the Bronsted acid-catalyzed reaction of an alcohol with a carboxylic acid to form an ester (see Table 1). Sulfuric acid is often the catalyst. Esters are widely used in the soap, perfume, and food industries. 

Fischer esterifications proceed very slowly in the absence of strong acids, but they reach equilibrium within a matter of a few hours when an acid and an alcohol are refluxed with a small amount of concentrated sulfuric acid or hydro n chloride. Since the position of equilibrium controls the amount of the ester formed, the use of an excess of either the carboxylic add or the alcohol increases the yield based on the limiting reagent. Just which component we choose to use in excess will depend on its availability and cost. The yield of an esterification reaction can also be ino-eased by removing water from the reaction mixture as it is formed. 

In 2008, the group of Williams [15] reported the first total synthesis of ( )-2-0-methylneovibsanin H (33) (Scheme 14.6). The diterpene, isolated from the leaves of Viburnum awabuki [16], was prepared by employing an acid-catalyzed domino sequence. Thus, the key transformation was the conversion of advanced intermediate 28 to cyclohexene 32 upon treatment with an excess of sulfuric acid in anhydrous methanol. Acid-mediated silyl deprotection first revealed alcohol 29, which readily underwent an intramolecular oxa-Michael addition to yield tricyclic 30. It was postulated that solvolysis and nucleophilic addition of methanol to the intermediary allyl cation then furnished acid 31, which underwent Fischer esterification. The resultant highly functionalized cyclohexene 32 was isolated in 50% yield as a mixture of diastereomers at C2 (diastereomeric ratio (dr) = 85 15). The observed stereochemistry at the newly created stereocenters, i.e., at C2 and C5, was postulated to arise from the preexisting sterically congested stereocenters in the starting material (i.e., 28). Cyclohexene 32 was eventually taken on to provide the natural... 

Treatment of a carboxylic acid with an alcohol in the presence of an acid catalyst—most commonly, concentrated sulfuric acid—gives an ester. This method of forming an ester is given the special name Fischer esterification after the German chemist Emil Fischer (1852-1919). As an example of Fischer esterification, treating acetic acid with ethanol in the presence of concentrated sulfuric acid gives ethyl acetate and water ... 

Fischer esterifications proceed very slowly in the absence of strong acids, but they reach equilibrium within a matter of a few hours when an acid and an alcohol are refluxed with a small amount of concentrated sulfuric acid or hydrogen chloride. Since the position of... 

When a carboxylic acid and an alcohol are mixed together, no reaction takes place. However, npon addition of catalytic amounts of a mineral acid, such as sulfuric acid or HCl, the two components combine in an equilibrium process to give an ester and water (Section 9-4). This method of ester formation was first described by the legendary (jerman chemist Emil Fischo-and his coworker Arthur Speier in 1895. It is therefore called Fischer-Speier or (more commonly) Fischer esterification. 

Thiopeptide antibiotics are a class of highly modified macrocyclic sulfur-containing peptides, and nearly all the thiopeptide antibioties identified to date inhibit protein synthesis in bacteria. The Bohlmann-Rahtz pyridine synthesis is a useful methodology in the synthetic approach for thiopeptide antibiotics.For example, one-step Bohlmann-Rahtz assembly of 189 and 190 in the presence of ammonium acetate in acetic acid at reflux afforded the corresponding pyridine-thiazole cores of thiopeptide antibiotics 191 in 63% yield.The TBS protecting group was also replaced by an acetate, probably as a consequence of acid-promoted cleavage and consequent Fischer-type esterification of the liberated alcohol. 

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