Carboxylic acid anhydrides mixed

Mixed anhydrides are prepared by reacting tellurinic anhydrides with carboxylic acids or anhydrides. ... 

In relation with the unique reactivity of N-(dialkylphosphoryl)amino acids mentioned above (see Sect. 3.2.3), a conversion of the carboxylic-phosphoric mixed anhydride 18f (R1 = R2 = alkyl) would provide an appealing pathway for the formation of the AT-phosphorylated derivatives. The reaction of NCAs might have then allowed a pathway for the formation of these versatile intermediates that can be useful for nucleotide ligation. 

Only a few examples of arenetellurinyl carboxylates, the mixed anhydrides of tellurinic acids and carboxylic acids, are known. These eompounds were prepared by refluxing mixtures of arenetellurinic acid anhydrides with acetic or trifluoroacetic acid or their anhydrides in chloroform . Acetonitrile and 1,2-dichloroethane were also used as solvents. Benzenetellurinyl trifluoroacetate is described as a very hygroscopic, intractable oil. The arenetellurinyl acetates are solids with melting points of approximately 150°. 

Acylations with carboxylic acids and anhydrides have been carried out with sulfuric acid as both solvent and catalyst, the reactive acylating agents from acyl halides probably being haloacyloxonium ions. Trifluoroacetic anhydride offers a rather milder reagent for reactions of carboxylic acids, with mixed anhydrides being likely intermediates. However, polyphosphoric acid remains the most widely used dehydrating agent for acylations by carboxylic acids. 

Derivatives of phosphinic acids have been used by Ramage and coworkers [116,117] in both solution and solid-phase approaches. The mechanism of the coupling was postulated to involve a carboxylic-iphosphinic mixed anhydride [116]. An advantage to these mixed anhydride intermediates in comparison with the biscarboxylic derivatives is regioselectivity. Bis-... 

The biomimetic phosphoric acid mixed anhydride concept stimulated further search for activating reagents that produce derivatives of acylamino acids (and peptides) in more simple ways than the ones mentioned earlier in the Chapter (on p. 78) An interesting attempt in this direction is the so called Bates reagent [47] which on reaction with carboxylic acids yields acyloxyphosphonium salts. 

Scheme 9.6. A cartoon representation of the enzyme (named glyceraldehyde-3-phosphate dehydrogenase, EC 1.2.1.12) catalyzed oxidation of the aldehyde glyceraldehyde-3-phosphate to the carboxylic acid-phosphoric acid mixed anhydride, 1,3-bisphosphoglycerate (which can be hydrolyzed to the corresponding carboxyhc acid and phosphoric acid). Start in a clockwise direction from the npper left.

The regioselective acylation of aromatic ethers with carboxylic acids (aromatic ether/carboxylic acid ratio =1) can be pafonned with an equimolecular mixture of trifluoroacetic anhydride adsorbed on the surface of alumina without any solvent [77]. The process can be applied, with nearly quantitative yields, to anisole and the three isomeric dimethoxybenzenes by using carboxylic acids. The authors outline that in the case of anisole, the acylation selectively occurs at the para position to the methoxy group. The reaction requires a large amount of alumina and trifluoroacetic anhydride, and consequently, it can only be appUed at the laboratory scale. The intervention of a mixed carboxyhc acidArifluoroacetic acid mixed anhydride intermediate is presumed. 

AijAT-dicyclohexylcarhodiimide (DCC) also leads to essentially quantitative conversion of amic acids to isoimides, rather than imides (30,31). Combinations of trifluoroacetic anhydride—triethjlarnine and ethyl chi oroform a te—triethyl amine also result in high yields of isoimides (30). A kinetic study on model compounds has revealed that isoimides and imides are formed via a mixed anhydride intermediate (12) that is formed by the acylation of the carboxylic group of amic acid (8). 

Carboxylic acids react with trifluoroacetic anhydride to give mixed anhydrides that are especially useful for the acylation of hindered alcohols and phenols ... 

Mixed anhydrides of a carboxylic acid and trifluoroacetic or triflic acids... 

Conversion of the carboxylic acid to the diethyl amide interestingly leads to an agent that exhibits the properties of a respiratory stimulant. One synthesis of this agent starts with the preparation of the mixed anhydride of nicotinic and benzene-sulfonic acid (4). An exchange reaction between the anhydride and diethyl benzenesulfonamide affords nikethemide (5). ... 

Preparation of 7-(D-0t-phenyigiycyiamido)-3-chioro-3-cephem-4-carboxyiic acid To a suspension of 280 mg (1.2 mmol) of 7-amino-3-chloro-3-cephem-4-carboxylic acid in 14 ml of acetonitrile was added with stirring at room temperature 0.5 ml of N, 0-bis-(trimethylsilyl)acetamide to form the soluble disilylmethyl derivative thereof. The solution was cooled to 0°C and was slowly added to a solution of the mixed anhydride formed by reacting 408 mg (1.5 mmol) of methyl-3-a-carboxybenzylaminocrotonate sodium salt with 161 mg (1.7 mmol) of methyl chloroformate in the presence to 2 drops of N, N-dimethylbenzyl amine in 7 ml of acetonitrile. 

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. 

To set the stage for the crucial aza-Robinson annulation, a reaction in which the nucleophilic character of the newly introduced thiolactam function is expected to play an important role, it is necessary to manipulate the methyl propionate side chain in 19. To this end, alkaline hydrolysis of the methyl ester in 19, followed by treatment of the resulting carboxylic acid with isobutyl chlorofor-mate, provides a mixed anhydride. The latter substance is a reactive acylating agent that combines smoothly with diazomethane to give diazo ketone 12 (77 % overall yield from 19). 

---