Carboxylic acids acid anhydride formation

Subsequently, it was shown that the reaction was catalyzed by base (48M(79)106). Dicyandiamide reacts with nitriles (the most valuable method), amidines, cyanamides, ammonia, cyanates, thiocyanates, carboxylic acids and anhydrides to yield 1,3,5-triazines (Table 13). This synthetic route has been reviewed thoroughly several times (59HC(13)1, p. 219,61MI22000, p. 650, 73ZC408). The base-catalyzed reaction of dicyandiamide with alkyl or aryl nitriles (Scheme 65) proceeds via the imino ether anion and the rate determining step is solvent dependent. In DMSO the formation of the imino ether is rate determining, but in 2-methoxyethanol the reaction between the anion and dicyandiamide controls the rate (66T157). 

Solutions of carboxylic acids or anhydrides in strong mineral acids also give rise to the protonation of the weaker component, but often the reaction goes further and leads to the formation of acylium ions. Thus, in the case of acetic acid dissolved in such strong acids as sulphuric, perchloric and trifluoromethanesulphonic acids, dehydration of the protonated species (ACOH2) gives the corresponding acetyl ester and/or its ionised form. The same endproduct is obtained if acetic anhydride is used instead of its acid ... 

The first (3-thiolactone was prepared according to Scheme A by Knunyants and co-workers. A mixed anhydride of )3-mercaptocarboxylic acid and carbonic-acid ester is obtained by treatment of a salt of the mercapto acid with a chlorocarbonate ester.Cyclization to the 3-thiolactone occurs during the reaction this synthetic method is exemplified by the preparation of 302 from 301. A mixed carboxylic-sulfonic acid anhydride is involved in the formation of the thiolactone ring in 303. ... 

Prepared by treatment of methyl formate with phosphorus pentachloride, the reagent reacts with a carboxylic acid or anhydride to give the corresponding acid chloride in high yield. Sulfonic acids or their sodium salts afford sulfonyl chlorides ... 

As with Co, Rh and Ir catalyze the olefin carbonylation reactions of hydrocarboxylation, hydroesterification and acid anhydride formation. Rhodium or Ir complexes and iodide promoters with HjO as the hydrogen source yields a mixture of linear and branched carbocylic acids the branched isomer predominates. Many soluble complexes, such as Irlj, Ir2(CO)4Br2, Rh(PPh3)2(CO)Cl or Ir[(C4H9)3P](CO)I can be utilized as a solution in a carboxylic acid solvent. The iodide source can be HI or any material which... 

Acid anhydride. Formation of a carboxylic acid anhydride. 

A related technique involves a tris(dimethylamino)phosphine-carbon tetrachloride reagent, where interaction with carboxylic acids gives anhydrides and tris(dimethylamino)phosphonium chloride (95), which can, in turn, activate remainingacid for furtherreaction, e.g. tocomplete anhydride formation, giving the overall process shown in Scheme 31. Alternatively, it can be used to effect amide-bond formation, when nucleophilic attack by amine on... 

Y asuharu Yoshimi and Minoru Hatanaka of the University of Fukui have described (Chem. Comm. 2007, 5244) a convenient procedure for the reductive decarboxylation of acids such as 21 to the corresponding alkane 22. Teruaki Mukaiyamaofthe Kitasato Institute, Tokyo has developed (Chemistry Lett. 2007, 36,1456) a simple protocol for the activation of carboxylic acids for amide formation. DMAP-mediated coupling of the acid with 25 gave the mixed anhydride, which combined efficiently with the amine 24 to give the amide 26. 

The p-functionalization of saturated esters first reported by Chi (see Section 14.6.4) is a very powerful methodology because it leads to the formation of a new C-C bond via the activation of a C-H bond on the otherwise unreac-tive p-carbon. This alkylation of homoenolates has since extended to other carbonyl compounds such as saturated carboxylic acids and anhydrides. Interestingly, saturated esters can also act as enolate precursors, leading to a-functionalization reactions, as shown by Chi in annulation reactions with a,p-unsaturated imines (Scheme 14.25). ... 

Acylation. A/-Acylation and related reactions ate brought about in straightforward ways with acyl chloride or acid anhydride, although the proximity of the carboxyl group may produce other reactions, eg, oxa2olinone formation, under some conditions. 

Anhydride Formation. The carboxyl group ia A/-protected amino acids is converted iato the symmetrical anhydride on treatment with the carbodiimide (84). 

CitroneUol is easUy esterified with acid anhydrides or carboxylic acids, catalyzed by mineral acids. The price of citroneUyl acetate [150-84-5] in 1995 was 10.45/kg (45). Other esters such as the formate and isobutyrate ate also used. 

By virtue of their fused /3-lactam-thiazolidine ring structure, the penicillins behave as acylating agents of a reactivity comparable to carboxylic acid anhydrides (see Section 5.11.2.1). This reactivity is responsible for many of the properties of the penicillins, e.g. difficult isolation due to hydrolytic instability (B-49MI51102), antibacterial activity due to irreversible transpeptidase inhibition (Section 5.11.5.1), and antigen formation via reaction with protein molecules. 

The reaction is not suitable for hindered carboxylic acids, since considerable symmetrical anhydride formation (52% with pivalic acid) results. Symmetrical anhydride formation can sometimes be suppressed by the use of stoichiometric quantities of DMAP. 

An example of this type of cyclization is the formation of 3-nitro-l,5-naph-thyridin-4(lH)-one (4) from 3-(/3-nitroethylideneamino)pyridine 2-carboxylic acid (3) by heating in acetic anhydride [56JCS(I)212]. No yields are given. 

This cyano-ester is hydrolysed by boiling with concentrated hydrochloric acid with the formationof pentane-ay -tricarboxylic acid, CO H. CH (CHj. CHj. COjH) andiwhen the sodium salt of this acid is heat with acetic anhydride and distilled, decomposition takes place with the formation of 8-ketohexahydrobenzoic acid or cyclohexanone-4-carboxylic acid—... 

Trifluoroacetic anhydride, which activates the polyesterification of 4-hy-droxybenzoic acid via the formation of a mixed anhydride,307 and 1,1 -carbonyldiimidazole308 were the first reported activating agents. The reaction between 1,1 -carbonyldiimidazolc and carboxylic acids proceeds through the formation of N-acylimidazolcs, which react with aliphatic diols in the presence of sodium ethoxide catalyst (Scheme 2.28). 

Similarly, triphenylphosphine dichloride (TPPCI2) can activate aromatic carboxylic acids in pyridine through the formation of acyloxyphosphonium salts (Scheme 2.30).313 A side reaction between tire intermediate acyloxyphosphonium species and a second carboxyl endgroup leading to the formation of anhydrides has been reported.313 This chain-limiting reaction decreases tire molar mass, while the presence of anhydride linkages in tire chains adversely affects the thermal and hydrolytic stability of the final polyester. 

Sulfur compounds have also been widely studied as activating agents for polyesterification reactions. p-Toluenesulfonyl chloride (tosyl chloride) reacts with DMF in pyridine to form a Vilsmeir adduct which easily reacts with carboxylic acids at 100-120° C, giving highly reactive mixed carboxylic-sulfonic anhydrides.312 The reaction is efficient both for aromatic dicarboxylic acid-bisphenol312 and hydroxybenzoic acid314 polyesterifications (Scheme 2.31). The formation of phenyl tosylates as significant side products of this reaction has been reported.315... 

Thionyl chloride is another activating agent employed for reactions between aromatic carboxylic acids and phenols in pyridine solution. The mechanism suggested does not involve the formation of an acid chloride but assumes the existence of an intermediary mixed sulfinic anhydride which undergoes reaction with phenolic endgroups (Scheme 2.32).311... 

Studies on Trifluoroacetic Acid. Part I. Trifluoroacetic Anhydride as a Promotor of Ester Formation between Hydroxy-Compounds and Carboxylic Acids, E. J. Bourne, M. Stacey, J. C. Tatlow, and J. M. Tedder, J. Chem. Soc., (1949) 2976-2979. 

First, the acid anhydride is produced by the reaction of the free acid with DCC. NucleophiUc attack by 4-pyrroUdinonepyridine on the anhydride results in the corresponding, highly reactive acylpyridinium carboxylate this leads to the formation of cellulose ester, plus a carboxylate anion. The latter imdergoes a DCC-mediated condensation with a fresh molecule of acid to produce another molecule of anhydride. N,N-carbonyldiimidazole (CDl) may substitute DCC for acid activation, the intermediate being N-acyhmidazol,... 

Unsymmetrical as well as symmetrical anhydrides are often prepared by the treatment of an acyl halide with a carboxylic acid salt. The compound C0CI2 has been used as a catalyst. If a metallic salt is used, Na , K , or Ag are the most common cations, but more often pyridine or another tertiary amine is added to the free acid and the salt thus formed is treated with the acyl halide. Mixed formic anhydrides are prepared from sodium formate and an aryl halide, by use of a solid-phase copolymer of pyridine-l-oxide. Symmetrical anhydrides can be prepared by reaction of the acyl halide with aqueous NaOH or NaHCOa under phase-transfer conditions, or with sodium bicarbonate with ultrasound. 

When an a-amino acid is treated with an anhydride in the presence of pyridine, the carboxyl group is replaced by an acyl group and the NH2 becomes acylated. This is called the Dakin-West reaction The mechanism involves formation of an oxazolone. The reaction sometimes takes place on carboxylic acids even when an amino group is not present. A number of N-substituted amino acids, RCH-(NHR )COOH, give the corresponding N-alkylated products. 

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