Mixed carboxylic anhydrides

Scheme 19 Selective acyl transfer in reductive hydroacylations involving mixed carboxylic anhydrides derived from pivalic acid...

Bis alkanoyl amino-2,4,6-triiodobenzyl esters Nanoparticulate diagnostic mixed carboxylic anhydrides... 

Hydrogenation of a mixture of styrenes ArCH=CH2 (or reactive alkenes, such as norbornene or ethylene) and symmetric or mixed carboxylic anhydrides [(RC0)20 or (RCO)O(COR )] in the presence of cationic rhodium catalysts ligated by triphenylar-sine (Ph3As), generates hydroacylation products ArCH(Me)COR as single regioiso-mers in high yields.108... 

Mixed pivalic anhydride 18 (42) is an example of selective mixed carboxylic anhydride. Selective aminolysis could be caused by the steric hindrance of the fert-butyl group. A mixed carbonic anhydride strategy has also been smdied to... 

The treatment of diethyl aroylphosphonates with 3-chloroperoxybenzoic acid yields diethyl aroyl phosphates (oxygen insertion) in 70-85% yields together with smaller amounts of mixed carboxylic anhydrides, ethyl benzoate and diethyl hydrogenphosphate (Scheme 31). The main reaction is a typical Baeyer-Villiger oxidation, applied here to an acylphosphonate The reaction generally has little value in the synthesis of acyclic mixed anhydrides, which are easily obtained by other procedures, but it is of value in some slightly modified but specific cases as, for example, in the synthesis of compounds in the 2,3-oxaphosphabicyclo[2.2.2]octane series (Section III.A.2). The 1 1 adducts of H-phospholes and A-phenylmaleimide (177) or dimers of the same phospholes (178 R =... 

A.R. Emery, V. Gold, Quantitative studies of the reactivities of mixed carboxylic anhydrides. Part. I. The composition of the acylation products in the reaction between acetic chloroacetic anhydrides and primary aromatic amines. J. Chem. Soc. 1950 1443-1447... 

The synthesis of (+)-N-methylmaysenine, a preliminary for the later synthesis of the antitumor agent maytansine, was accomplished by the joining of fragments A and B, chain extension and macrolactam closure using a mixed carboxylic-sulfonic acid anhydride. 

These authors suggest that the reaction may proceed through the formation of their mixed anhydrides , and illustrate a metal ion templated, mixed carboxylic-sulfonic anhydride. 

As shown in Figure 16.10, this reaction mechanism involves nucleophilic attack by —SH on the substrate glyceraldehyde-3-P to form a covalent acylcysteine (or hemithioaeetal) intermediate. Hydride transfer to NAD generates a thioester intermediate. Nucleophilic attack by phosphate yields the desired mixed carboxylic-phosphoric anhydride product, 1,3-bisphosphoglycerate. Several examples of covalent catalysis will be discussed in detail in later chapters. 

On the other hand, 1 g of 7-amino-3-methyl-3-cephem-4-carboxylic acid was suspended in 20 ml of methanol, and 1.4 g of triethylamine was added thereto to be dissolved, and 0,4 ml of acetic acid was further added thereto. This solution was cooled to -20°C and the mixed acid anhydride prepared previously was added thereto. After the mixture was reacted at -20°C for 1 hour, the temperature of the reaction mixture was raised to 0°C over a period of 1 hour, and the mixture was reacted for 3 hours at the same temperature. 

Like all anhydrides (Section 21.5), the mixed carboxylic-phosphoric anhydride is a reactive substrate in nucleophilic acyl (or phosphoryl) substitution reactions. Reaction of 1,3-bisphosphoglycerate with ADR occurs in step 7 by substitution on phosphorus, resulting in transfer of a phosphate group to ADP and giving ATP plus 3-phosphoglycerate. The process is catalyzed by phospho-gjvcerate kinase and requires Mg2+ as cofactor. Together, steps 6 and 7 accomplish the oxidation of an aldehyde to a carboxylic acid. 

The synthesis of key intermediate 12, in optically active form, commences with the resolution of racemic trans-2,3-epoxybutyric acid (27), a substance readily obtained by epoxidation of crotonic acid (26) (see Scheme 5). Treatment of racemic 27 with enantio-merically pure (S)-(-)-1 -a-napthylethylamine affords a 1 1 mixture of diastereomeric ammonium salts which can be resolved by recrystallization from absolute ethanol. Acidification of the resolved diastereomeric ammonium salts with methanesulfonic acid and extraction furnishes both epoxy acid enantiomers in eantiomerically pure form. Because the optical rotation and absolute configuration of one of the antipodes was known, the identity of enantiomerically pure epoxy acid, (+)-27, with the absolute configuration required for a synthesis of erythronolide B, could be confirmed. Sequential treatment of (+)-27 with ethyl chloroformate, excess sodium boro-hydride, and 2-methoxypropene with a trace of phosphorous oxychloride affords protected intermediate 28 in an overall yield of 76%. The action of ethyl chloroformate on carboxylic acid (+)-27 affords a mixed carbonic anhydride which is subsequently reduced by sodium borohydride to a primary alcohol. Protection of the primary hydroxyl group in the form of a mixed ketal is achieved easily with 2-methoxypropene and a catalytic amount of phosphorous oxychloride. 

Other examples of the photochemical a-cleavage of cyclic sulfoxides have been noted. Lawesson and coworkers22 have proposed that the mixed sulfenic-carboxylic anhydride (16) is formed on photolysis of 17, by a-cleavage followed by the loss of benzaldehyde. The... 

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... 

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. 

Another useful reagent for amide formation is compound 1, known as BOP-C1,141 which also proceeds by formation of a mixed carboxylic phosphoric anhydride. 

Several successful cyclizations of quite complex structures were achieved using polyphosphoric acid trimethylsilyl ester, a viscous material that contains reactive anhydrides of phosphoric acid.58 Presumably the reactive acylating agent is a mixed phosphoric anhydride of the carboxylic acid. 

Intramolecular acylations are very common, and the normal conditions involving an acyl halide and Lewis acid can be utilized. One useful alternative is to dissolve the carboxylic acid in polyphosphoric acid (PPA) and heat to effect cyclization. This procedure probably involves formation of a mixed phosphoric-carboxylic anhydride.54... 

Phenylcyclopentanecarboxylic acid, with ethyl chlorocar-bonate to give mixed carboxylic-carbonic anhydride, 51, 48... 

Sodium, with l-bromo-3-chloro-cyclobutane to give bicyclo [l.l.O]butane, 51, 55 Sodium amalgam, 50, 50, 51 Sodium amide, with 2,4-pentane-dione and diphenyliodonium chloride to give l-phenyl-2, 4-pentanedione, 51, 128 Sodium azide, 50, 107 with mixed carboxylic-carbonic anhydrides, 51, 49 Sodium borohydride, reduction of erythro-3-methanesulfony-loxy-2-butyl cyclobutanecar-boxylate, 51, 12 reduction of 2-(1-phenylcyclo-pentyl)-4,4,6-trimethyl-5,6-dihydro-1,3(4H)-oxazine to 2-(1-phenylcyclopentyl)-4,4, 6-trimethyltetrahydro-l,3-oxazine, 51, 25 Sodium cyanoborohydride, used... 

The carbonyl group of an acid chloride is also a sufficiently electropositive center that acylation of a sulfinate ion occurs at oxygen (123) rather than sulfur (Schank, 1967 Kobayashi, 1966b). The mixed sulfinic-carboxylic anhydrides... 

FMF Chen, M Slebioda, NL Benoiton. Mixed carboxylic-carbonic acid anhydrides of acylamino acids and peptides as a convenient source of 2,4-dialky 1 -5(AH)-oxazo-lones. Int J Pept Prot Res 31, 339, 1988. 

A variant that eliminates the production of water and that has proved effective for esterification of hydroxy and aromatic amino acids involves the use of thionyl chloride instead of acid. At a low temperature, the alcohol reacts with the chloride, generating methyl sulfinyl chloride, which produces the ester, probably through the mixed carboxylic acid-sulfinic acid anhydride (Figure 3.18, B). p-Toluenesulfonyl chloride added to the acid and benzyl alcohol serves the same purpose in the preparation of benzyl esters. 

S Kim, JL Lee, YC Kim. A simple and mild esterification method for carboxylic acids using the mixed carboxylic-carbonic anhydrides. J Org Chem 50, 560, 1985. 

DS Tarbell, EJ Longosz. Thermal decomposition of mixed carboxylic-carbonic anhydrides. Factors affecting ester formation. J Org Chem 24, 774, 1959. 

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