Carboxylic acids reaction with alcohols under acid catalysi

Although the above reactions are common to alcohols and phenols, there are several reactions that can be done on alcohols but not phenols, and vice versa. For example, unlike alcohols, phenols cannot be converted to esters by reaction with a carboxylic acid under acid catalysis. Reactions involving the cleavage of the C-O bond are also not possible for phenols. The aryl C-O bond is stronger than the alkyl C-O bond of an alcohol. 

It is for this reason that alcohols will react with carboxylic acids under acid catalysis. The acid (usually HCl or H2SO4) reversibly protonates a small percentage of the carboxylic acid molecules, and the protonated carboxylic acids are extremely susceptible to attack by even a weak nucleophile such as an alcohol. This is the first half of the reaction ... 

Imidazolides of aromatic sulfonic acids react much more slowly in alcoholysis reactions than the carboxylic acid imidazolides. Although the reaction with phenols is quantitative when a melt is heated to 100 °C for several hours, with alcohols under these conditions only very slight alcoholysis is observed. In the presence of 0.05 equivalents (catalytic amount) of sodium ethoxide, imidazole sodium, of NaNH2, however, imidazolides of sulfonic acids react with alcohols almost quantitatively and exothermically at room temperature in a very short time to form sulfonic acid esters (sulfonates). (If the ratio of sulfonic acid imidazolide to alcoholate is 1 2, ethers are formed see Chapter 17). The mechanism of catalysis by base corresponds to that operative in the synthesis of carboxylic esters by the imidazolide method. Because of the more pronounced nucleophilic character of alkoxide ions, sulfonates can also be prepared in good yield by alcoholysis of their imidazolides in the presence of hydroxide ions i.e., with alcoholic sodium hydroxide. 45 Examples of syntheses of sulfonates are presented below. 

Buffer catalysis of the hydrolysis of phenyl (311 R = Ph) and methyl (311 R = Me) benzenesulfinates to give the sulfinic acid (312) and alcohol ROH is strongly accelerated by both carboxylate and amine components of the buffer which give Bronsted /i values of approximately unity on separate lines. The carboxylates are about 44 tunes more effective than amines of similar basicity. A concerted. S n2 mechanism with a hypervalent intermediate (313) is proposed for the nucleophilic reaction of these esters.286 The reaction of the thiosulfinate esters (314) with sulfenyl chlorides RSCI and sulfenate esters (315) to give sulfinyl chlorides and disulfides and sulfinate esters and disulfides, respectively, has been studied.287 Hydrolysis of 2-(3-aminophenyl)sulfonyl-ethanol hydrogensulfate gives under different conditions various products such as the ether (316) and the sulfone (317).288... 

You remember, of course, that esters can be made from carboxylic acids and alcohols under acid catalysis, so you might expect them to use this type of method. On a small scale, it s usually better to convert the acid to an acyl chloride before coupling with an alcohol, using pyridine (or DMAP + Et3N) as a base this type of reaction might have been a reasonable choice too. 

Ester formation is a standard organic reaction between an alcohol and a carboxylic acid, which is an equilibrium reaction that has been shown to occur under catalysis by either acid or base. In polyesterification involving an organic acid, the substrate is itself the catalyst. It has been noted (Pilati, 1989) that, among the many reaction mechanisms, Scheme 1.1 is the most likely for acid-catalysed esterification, with the second reaction being the rate-determining step. 

Extension of the enamine-mediated carbonyl a-amination strategy to the generation of quaternary stereogenic centers at the a-position of a-branched aldehydes under catalysis by prohne 1 [8, 9], pyrrolidine tetrazole 3 [10, 11], or L-azetidin-2-carboxylic acid 4 [8] has also been explored (Table 11.1). The observed enantio-selectivities ranged from essentially none to >99%. Derivatives of 2-phenylpropanal gave better enantioselectivities than a,a-dialkyl substituted aldehydes. Erase and coworkers [11] employed microwave irradiation to accelerate the rate of proline-catalyzed amination, and found that yields as well as enantioselectivity can be somewhat improved with shorter reaction times. It appears that the pyrrolidine tetrazol 3 was a more effective catalyst than L-proline 1 for the amination of 2-phenylpropanal derivatives [10,11]. Subsequent reduction of adducts and cyclization could be carried out to afford the respective a-amino alcohols or the A-amino-oxazolidinones. 

Attempts to achieve selective oxidations of hydrocarbons or other compounds when the desired site of attack is remote from an activating functional group are faced with difficulties. With the powerful transition-metal oxidants, the initial oxidation products are almost always more susceptible to oxidation than the starting material. Once a hydrocarbon is attacked, it is likely to be oxidized to a carboxylic acid, with chain cleavage by successive rapid oxidation of alcohol and carbonyl intermediates. There are a few circumstances under which oxidations of hydrocarbons can be synthetically useful processes. One group involves catalytic industrial processes. Much work has been expended on the development of selective catalytic oxidation processes and several have attained economic importance. Since the mechanisms are often obscured by limited understanding of heterogeneous catalysis, however, we will not devote additional attention to these reactions. 

Esters can be prepared by reaction of alcohols with carboxylic acids under acidic catalysis but can be hydrolyzed in either acid or basic solution. They can also be prepared by reaction of alcohols with acid chlorides or anhydrides. 

Although the hydrolysis of alkyl halides to alcohols has been extensively investigated, an alternative two-step sequence involving substitution with carboxylate ion is more practical for the preparation of alcohols. Activation of the carboxylate anion prepared by the reaction of the acid with a base can be achieved (i) by use of a polar aprotic solvent and (ii) by use of aprotic apolar solvents under phase transfer catalysis, polymer conditions, or with crown ethers. 

The release of the phenol is much more rapid than in similar esters lacking the imidazole group. The neighboring basic nitrogen of the imidazole ring is a much more effective nucleophile toward the carbonyl center than water or the hydroxide ion under the conditions of the reaction. As in the case of carboxylate catalysis, nucleophilic catalysis is important only with esters derived from rather acidic alcohols, and most of the studies have been done with phenyl esters. 

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