Reactions of Anhydrides

Although somewhat less reactive than acid chlorides, anhydrides nonetheless readily react with most nucleophiles to form substitution products. Nucleophilic substitution reactions of anhydrides are no different than the reactions of other carboxyUc acid derivatives, even though anhydrides contain two carbonyl groups. Nucleophilic attack occurs at one carbonyl group, while the second carbonyl becomes part of the leaving group. 

A short laboratory synthesis of blattellaquinone (Problem 22.15), the sex pheromone of the female German cockroach, opens new possibilities for cockroach population control using pheromone-baited traps. 

Nucleophilic substitution occurs only when the leaving group is a weaker base and therefore a better leaving group than the attacking nucleophile. 

Anhydrides can t be used to make acid chlorides, because RCOO is a stronger base and therefore a poorer leaving group than Cr. Anhydrides can be used to make all other acyl derivatives, however. Reaction with water and alcohols yields carboxylic acids and esters, respectively. Reaction with two equivalents of NH3 or amines forms 1°, 2°, and 3° amides. A molecule of carboxylic acid (or a carboxylate salt) is always formed as a by-product. 

Replacing NH3 with a 1 ° or 2° amine forms a 2° or 3° amide, respectively. 

Problem 22.16 Draw the products formed when benzoic anhydride [(C6H5C0)20] is treated with each nucleophile (a) H2O, pyridine (b) CH3OH (c) NH3 (excess) (d) (CH3)2NH (excess). 

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The reaction of anhydrides with aryl azides, in the presence of McaSiCl and Nal, gives N-aryl imides. 

The Diels-Alder reactions of anhydrides based on a dibenzobicyclo[2.2.2]octatriene motif 88a-88e, as non-sterically biased dienophiles, were studied [151]. 

The changes in the IR spectra of the copolymer exposed to UV irradiation suggest the formation of coordination-bound organotin fragments due to complex intermolecular reactions of anhydride and organotin units. 

Then, it appears, that photochemical cross-linking of an organotin copolymer is the result of complex supramolecular conversions and intermoleeular reactions of anhydride and organotin units involving the formation of transverse coordination-bound organotin carboxylate fragments 109). 

Acylation of triazole is generally facile and can be performed by reaction of anhydrides or acyl halides with triazolates or by treatment of triazoles with acyl halides in an inert solvent. Carbonylditriazole (59) reacts with benzoyl chloride to give 1-benzoyltriazole (60) via transacylation (Equation (21)) <62CB1275>. 

Reaction of anhydrides. Anhydrides react rapidly to form esters, amides, N-substituted amides, and carboxylic acids. 

Aromatic carboxylic anhydrides can be used for the Fleck reaction without adding a base. The reaction of benzoic anhydride (37) with acrylate proceeds in the presence of 1.0 mol % of NaBr without phosphine ligand in NMP at 160 °C [23]. The reaction of anhydrides in the absence of bases, and hence without forming halide salts after the reaction, is attractive from a practical standpoint. 

The reaction of anhydrides with epoxy groups is complex, with several competing reactions capable of taking place. The most significant reaction mechanisms are as follows ... 

Reactions of Anhydrides Anhydrides undergo many of the same reactions as acid chlorides. Like acid chlorides, anhydrides are easily converted to less reactive acid derivatives. 

Most reactions of anhydrides involve loss of one of the two acid molecules as a leaving group. If a precious acid needs to be activated, converting it to the anhydride would allow only half of the acid groups to react. Converting the acid to an acid chloride... 

Reactions Of anhydrides. Treatment of 2,3-pyridinedicarboxylic anhydride with methanol leads to the formation of 2-(methoxycarbonyl)nicotinic acid <2003TL2745>. 

The mechanism of high-temperature, base-catalyzed esterification involves cyclic anhydride formation by the polycarboxylic acid, followed by base-catalyzed reaction of anhydride groups with cellulosic hydroxyls. Fumaric acid, which cannot form a cyclic anhydride because of the trans arrangement of the two carboxyl groups, fails to react with cotton in the presence of weak bases and heat. 

Polymers with pendant groups that are derivatives of carboxylic acid can he hydrolyzed to yield poly(acrylic acid). This includes polymers like polyacrylamide, polyacrylonitrile, and polyacrylates. When heated, poly(acrylic acid) form polymeric anhydrides, which undergo typical reactions of anhydrides, such as hydrolysis, alcoholysis, and amidation. 

The preparation of some esters from the reactions of anhydrides has been described in Section 1C(4) and 2,3-dicarboxypyrazine anhydride with 2-dibutylamino-ethanol in refluxing benzene gave 2-carboxy-3-(2 -dibutylaminoethoxy)carbonyl-pyrazine (1278). 

Further studies on the reactions of anhydrides with carboxylic acids in the presence of a palladium catalyst led to the discovery of the direct hydrogenation of carboxylic acids into aldehydes. The catalytic process provides new means of synthesizing various aldehydes from carboxylic acids (Eq. 31) [77]. 

Cyclopropyl methyl ketones have also been obtained by reaction of anhydrides of cyclo-propanecarboxylic acids with methyllithium. ... 

The formation of compatibilizer frequently occurs by interfacial reaction of the modified polymers. An example is the use of maleic anhydride grafted to a polyolefin elastomer (EPM/EPM-g-MA) as the interfacial additive for reactive blending with a polyamide, nylon-6 (Van Duin et al., 2001), in a twin-screw extruder. It was found that the consumption of MA occurred rapidly and different blend morphologies were produced. However, it was found that the nylon-6 degraded during processing, due to the reaction of anhydride with the... 

Bolm51 was able to improve matters by piling in the quinine (so that over an equivalent was used -110 %) which enabled the reaction of anhydride 223 to be done at a lower temperature (giving a better ee) in a mere 1.5 days. The pseudo-enantiomer quinidine could also be used to give ester 224. A range of rings 225 to 229 works. 

Both acid chlorides, including ethylsuccinyl chloride," and acid anhydrides "-" have been used as acylating agents, as have carbamoyl chlorides. Silver-assisted reactions of anhydrides of a-bromo-toluic acid also lead to alkynic ketones, probably via an intermediate acyloxyalkyloxycarbenium salt (Scheme 26). ... 

Sulfur tetrafluoride and F2 gas are among other fluorinating agents used for the synthesis of fluorinated ethers. For example, F-oxane was reported to form in the reaction of anhydride of F-glutaric acid or F-glutaryl fluoride with excess of SF4. Perfluorinated spiro-ethers 19 were prepared in high yield by exhaustive fluorination of the parent hydrocarbons using elemental fluorine. 

The dienophilic properties of vinylene carbonate (1,3-dioxol-2-one, 6) have been repeatedly exploited for the synthesis of cyclic polyols. Recently a number of ribofuranose derivatives have been synthesized starting from 6. The known adduct 7, obtained from 6 and furan, was c/r-hydroxylated, and after acetonation was hydrolyzed with base and cleaved with permanganate to give the dicarboxylic acid 8. The corresponding anhydride 9 gave, on treatment with trimethylsilyl azide, the isocyanate 10, which in turn was converted into the carbonate 11 on addition of methanol. The monoester 12, obtained in the reaction of anhydride 9 with isopropanol, was effectively resolved into enantiomers by the use of brucine or (/ )-l-(2-naphthyl)ethylamine. ... 

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