Phosphoric sulfonic anhydrides

The condensation reactions are preferentially carried out in pyridine. As reactive species for phosphorylation of the nucleoside R OH (synthesis of a phosphortriester), the phosphoric acid azolide has been assumed. The mixed phosphoric sulfonic anhydride and a pyrophosphate tetraester have been suggested as intermediates leading to the phosphoric acid azolide. 

Phosphoric-sulfonic anhydrides are of special interest because they are presumed to be intermediates in oligonucleotide coupling reactions involving phosphordiester activation by arenesulfonyl derivatives (see Section 12.7). 

However, this method is not suitable for the preparation of phosphonic- or phosphoric-sulfonic anhydrides. 1505... 

Several methods of activation of the acid functional group have been described (hydroxypiperidine, thiophe-nol, thiazolidine-2-thione.). Mixed anhydride methods (phosphonic, phosphoric, sulfonic, carbonic anhydrides) have been used in the final steps of many impressive total syntheses (rifamycin S for example). 

The synthesis of 2,4-dihydroxyacetophenone [89-84-9] (21) by acylation reactions of resorcinol has been extensively studied. The reaction is performed using acetic anhydride (104), acetyl chloride (105), or acetic acid (106). The esterification of resorcinol by acetic anhydride followed by the isomerization of the diacetate intermediate has also been described in the presence of zinc chloride (107). Alkylation of resorcinol can be carried out using ethers (108), olefins (109), or alcohols (110). The catalysts which are generally used include sulfuric acid, phosphoric and polyphosphoric acids, acidic resins, or aluminum and iron derivatives. 2-Chlororesorcinol [6201-65-1] (22) is obtained by a sulfonation—chloration—desulfonation technique (111). 1,2,4-Trihydroxybenzene [533-73-3] (23) is obtained by hydroxylation of resorcinol using hydrogen peroxide (112) or peracids (113). 

For lab prepns, and occasionally in industrial use, more expensive nitrating agents may be employed, as for example solns of nitric acid in inert organic solvents (chlf, carbon tetrachloride, eth, nitromethane, etc), or a soln of nitric acid in phosphoric or acetic acids or in acetic anhydride, trifluoroacetic anhydride or trifluoro-me thane sulfonic acid (Ref 94)... 

Mixed Anhydrides of Phosphoric, Phosphonic, and Phosphinic Acids with Sulfonic Acids... 

Mixed anhydrides between phosphoric, phosphonic, and phosphinic acids on one side and sulfonic or carboxylic acids on the other are conveniently prepared via phosphor-azolides.[150]... 

A. Trifluoromethanesulfonic Anhydride. To a dry, 100-ml., round-bottomed flask are added 36.3 g. (0.242 mole) of trifluoromethane-sulfonic acid (Note 1) and 27.3 g. (0.192 mole) of phosphorus pentoxide (Note 2). The flask is stoppered and allowed to stand at room temperature for at least 3 hours. During this period the reaction changes from a slurry to a solid mass. The flask is fitted with a short-path distilling head and then heated first with a stream of hot air from a heat gun and then with the flame from a small burner. The flask is heated until no more trifluoromethanesulfonic anhydride distills, b.p. 82-115°. The yield of the anhydride, a colorless liquid, is 28.4-31.2 g. (83-91%). Although this product is sufficiently pure for use in the next step of this preparation, the remaining acid may be removed from the anhydride by the following procedure. A slurry of 3.2 g. of phosphorous pentoxide in 31.2 g. of the crude anhydride is stirred at room temperature in a stoppered flask for 18 hours. After the reaction" flask has been fitted with a short-path distilling head, it is heated with an oil bath to distill iD.7 g. of forerun, b.p. 74—81°, followed by 27.9 g. of the pure trifluoromethanesulfonic acid anhydride, b.p. 81-84° (Note 3). 

A.7.1 Esterification of Acids using Carbodiimides. The formation of anhydrides from carboxylic acids, thiocarboxylic acids, sulfonic acids and phosphorous acids are discussed in Section 2.4.S.2. In this section only special cases of anhydride formation are described. Mixed anhydrides of amino acids and adenylic acid are produced from the corresponding acids using DCC as the condensation agent. ° Mixed anhydrides not containing amino acids, such as butyryl adenate, adenosine 5 -phosphosulfate and p-nitrophenyl-thymidine-5-phosphate are also obtained. 

Sn[N(TMS)2l2, A, A -carbonyldiimidazole (110, p. 1418), which behaves as in reaction 16-63, POCl3, °" TiCl4, ° molecular sieves,Lawesson s reagent (p. 1278), ° and (MeO)2POCl. ° Certain dicarboxylic acids form amides simply on treatment with primary aromatic amines. In these cases, the cyclic anhydride is an intermediate and is the species actually attacked by the amine. Carboxylic acids can also be converted to amides by heating with amides of carboxylic acids (exchange),sulfonic acids, or phosphoric acids, for example, ... 

Friedel-Crafts Acylation of Cedrene. Let us now look in a little more detail at the Friedel-Crafts acylation of cedrene. This reaction can be carried out using acetic acid or acetic anhydride with an acid catalyst such as formic acid, phosphoric acid or sulfuric acid. The species which attacks the double bond of cedrene is the protonated acid or anhydride molecule. When sulfuric acid is used as a catalyst with acetic anhydride as the reagent, it is thought that the sulfuric acid first sulfonates the acetic anhydride to give sulfoacetic anhydride (6.122) as the acylating species. This results in a faster reaction as the sulfoacetate anion (6.126) is a... 

Sulfonyl chlorides are also used as coupling agents. Those most commonly encountered are methanesulfonyl chloride (MS), mesitylsulfonyl chloride, and triisopropylbenzenesulfonyl chloride (TPS). These reagents function by formation of mixed sulfonic-phosphoric anhydrides, which then react with the free nucleophilic hydroxyl group to give phosphorylated product. 

Reactions of Carboxylic, Phosphoric, and Sulfonic Acids and their Derivatives 59 (c) Acids and anhydrides... 

Anhydrides and esters of phosphoric acid dominate the organic chemistry of the biological world. In contrast, phosphates are rarely used in organic chemistry in the laboratory. Instead, we have seen that the preferred leaving groups in nonbiological reactions are such things as halide ions and sulfonate ions (Sections 9.1 and 11.3). 

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