Carboxylic acid anhydrides, protonated

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

An extensive nmr study of the protonation of acyclic carboxylic acid anhydrides in HSO3F—SbFs—SO2 solution at —70°C has proved the formation of carbonyl-protonated anhydrides [206],... 

Carboxylic acid anhydrides cleave immediately when protonated even in HSC F-SbFs solution at low temperature (—80°C).541 569 Monoprotonated anhydrides 291, however can easily be generated reacting oxocarbenium ions (acyl cations) with carboxylic acids in SO2 solution. Rapid intramolecular proton transfer between the carbonyl groups was observed by NMR. 

The first reagent combination, carboxylic acid chloride/A1C13, reacts via the A1C13 complex A of the acid chloride or via the acylium tetrachloroaluminate B formed from it by /)-elimination. A carboxylic acid anhydride and A1C13 react via analogous electrophiles, namely via the A1C13 complex D of the anhydride or via the acylium salt E formed therefore by a /T elimination. The protonated anhydride F and the protonated carboxylic acid C are the reactive electrophiles of the Friedel-Crafts acylations catalyzed by Bronsted acids. 

Proton sponge analogues with /V-acyl substituents are commonly prepared by treatment of l-dimethylamino-8-methylaminonaphthalene (6) with the corresponding carboxylic acid anhydride, as in the case of 8543, or with acyl chloride, as for 86 and 8766. 

Water is a good solvent for most biomolecules, which are generally charged or polar compounds. Solubilization of compounds with functional groups such as ionized carboxylic acids (COOQ, protonated amines (NH3+), phosphate esters, or anhydrides is also a result of hydration and charge screening. 

Olah GA, Dunne K, Mo YK, Szilagyi PJ (1972) Stable carbocations. CXXVin protonated acyclic carboxylic acid anhydrides and their cleavage to oxocarbenium ions. Question of the formyl cation in superacid media. J Am Chem Soc 94 4200-4205... 

Proton-initiated polymerization of THF in the presence of carboxylic acid anhydrides gives ester-terminated end groups. 

Carboxylic Acid Anhydrides. The replacement of the proton attached to the oxygen in the carboxylic acid functional group (-CO2H) by an acyl group produces the derivative called a carboxylic anhydride. There are, of course, two possibilities for carboxylic anhydrides of the general form RC0(0)0CR or (RC0)20 since the R groups can be the same as each other or they can be different from each other. 

The process of substitution undertaken on carboxylic acids and the derivatives of carboxylic acids (anhydrides, acid halides, esters, amides, and nitriles) generally involves a series of replacement processes. Thus, individually, substitution may involve replacement of (a) the proton attached to oxygen of the -OH group (i.e., ionization of the acid) (b) the hydroxyl (-OH) portion of the carboxylic acid (or derivative) (e.g., esterification) (c) the carbonyl oxygen and the hydroxyl (-OH) (e.g., orthoester formation, vide infra) (d) the entire carboxylic acid functionality (e.g., the Hunsdiecker reaction, already discussed Scheme 9.101) and the decarboxylation of orotic acid (as orotidine monophosphate) to uracil (as uridine monophosphate)—catalyzed by the enzyme orotidine monophosphate decarboxylase (Scheme 9.115) or (e) the protons (if any) on the carbon to which the carboxylic acid functional group is attached (e.g., the Dieckman cycUzation, already discussed earlier, c Equation 9.91). Indeed, processes already discussed (i.e., reduction and oxidation) have also accomplished some of these ends. Some additional substitutions for the carboxylic acid group itself are presented in Table 9.6, while other substitutions for derivatives of carboxylic acids are shown in Tables 9.7-9.10 and discussed subsequently. 

Many compounds contain more than one functional group Prostaglandin Ei a hormone that regulates the relaxation of smooth muscles con tains two different kinds of carbonyl groups Classify each one (aldehyde ketone carboxylic acid ester amide acyl chloride or acid anhydride) Identify the most acidic proton in prostaglandin Ei and use Table 1 7 to estimate its pK ... 

Ion 21 can either lose a proton or combine with chloride ion. If it loses a proton, the product is an unsaturated ketone the mechanism is similar to the tetrahedral mechanism of Chapter 10, but with the charges reversed. If it combines with chloride, the product is a 3-halo ketone, which can be isolated, so that the result is addition to the double bond (see 15-45). On the other hand, the p-halo ketone may, under the conditions of the reaction, lose HCl to give the unsaturated ketone, this time by an addition-elimination mechanism. In the case of unsymmetrical alkenes, the attacking ion prefers the position at which there are more hydrogens, following Markovnikov s rule (p. 984). Anhydrides and carboxylic acids (the latter with a proton acid such as anhydrous HF, H2SO4, or polyphosphoric acid as a catalyst) are sometimes used instead of acyl halides. With some substrates and catalysts double-bond migrations are occasionally encountered so that, for example, when 1 -methylcyclohexene was acylated with acetic anhydride and zinc chloride, the major product was 6-acetyl-1-methylcyclohexene. ... 

Acyl halides and anhydrides are the most reactive class of carboxylic acid derivatives, and readily react with amines to give amides. It should be noted that in both cases the leaving group is a conjugate base that, upon protonation during the reaction, will become an... 

A-Acyloxypyridinium salts can be isolated from the reaction of A-oxides with acid anhydride by the inclusion of a strong acid possessing a non-nucleophilic anion, e.g. HCIO4. Such acids will protonate the initially formed carboxylate ion and provide a stable anion for salt formation (Scheme 115) (65JOC1909). 

Proton acids can be used as catalysts when the reagent is a carboxylic acid. The mixed carboxylic sulfonic anhydrides RCOOSO2CF3 are extremely reactive acylating agents and can smoothly acylate benzene without a catalyst.265 With active substrates (e.g., aryl ethers, fused-ring systems, thiophenes), Friedel-Crafts acylation can be carried out with very small amounts of catalyst, often just a trace, or even sometimes with no catalyst at all. Ferric chloride, iodine, zinc chloride, and iron are the most common catalysts when the reactions is carried out in this manner.266... 

Chlorinated Fatty Acids. Chlorination of carboxylic acids is much more difficult because the contribution or the carbonyl group toward proton removal is offset by the electron donation effect from the hydroxyl group. This hindrance is obviated by reaction with the acid chloride or anhydride. Chlorination is normally accomplished hy use of n catalyst, such as phosphorus trichloride. Monochloroacelic acid is an important industrial chemical. Dichloro- and trichloroacetic acids can he produced by further chlorination, although the latter can be produced convenienlly by nitric acid oxidation of chloral. Higher chlorinalcd tally acids can be produced by treatment or the hydroxy carboxylic acid or ester with HCI ur PCL ... 

The acylating reagents commonly used are carboxylic acid halides, RCOC1, anhydrides, (RC0)20, or the acid itself, RC02H. A strong proton or other Lewis-acid catalyst is essential. The catalyst functions to generate the acyl cation ... 

Thus, on heating perchlorates of 5-alkoxy-l-aminonaphthalene 125 (R = Me, Et) with alkyl carboxylic anhydrides in the presence of catalytic ammounts of perchloric acid, N-protonated 2-alkyl-benzo[cd]indolium... 

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