Anhydrides, mixed sulfonic

A variety of coupling methods have been employed including acid chlorides, mixed anhydrides, mixed sulfonic acid anhydrides,... 

Ethers. In the presence of anhydrous agents such as ferric chloride (88), hydrogen bromide, and acid chlorides, ethers react to form esters (see Ethers). Esters can also be prepared from ethers by an oxidative process (89). With mixed sulfonic—carboxyhc anhydrides, ethers are converted to a mixture of the corresponding carboxylate and sulfonate esters (90) ... 

An important role must be attributed to intermediate mixed anhydrides of sulfonic acids and mineral acids sulfonic acid anhydrides are reported to need Friedel-Crafts conditions to generate sulfones327,476. Instead of arenesulfonic acids, their methyl esters may undergo insertion of sulfur trioxide477,478 yielding mixed anhydrides, which in turn furnish... 

As an alternative, Harpp and coworkers reacted benzenesulfinyl chloride with the trimethylsilyl derivative of menthol to form the diastereomeric esters in 91% yield the epimer of configuration R could be isolated by crystallization in unspecified yield. Grossert and coworkers prepared ester 19 in 51% yield as a mixture of diastereomers by treating p-toluenesulfonyl chloride with sodium p-toluenesulfinate in DMF containing menthol. It was postulated that initial nucleophilic attack by the sulfinate oxygen on the sulfonyl sulfur atom gave the mixed sulfonate-sulfinate anhydride 21, which then reacted... 

R" may be alkyl or aryl. For dialkyl ethers, the reaction does not end as indicated above, since R OH is rapidly converted to R OR by the sulfonic acid (reaction 0-16), which in turn is further cleaved to R 0S02R" so that the product is a mixture of the two sulfonates. For aryl alkyl ethers, cleavage always takes place to give the phenol, which is not converted to the aryl ether under these conditions. Ethers can also be cleaved in a similar manner by mixed anhydrides of sulfonic and carboxylic acids733 (prepared as in 0-33). p-Hydroxy alkyl perchlorates734 and sulfonates can be obtained from epoxides.735 Epoxides and oxetanes give dinitrates when treated with N2Os,736 e.g.,... 

In a model study for erythronolide B, White et al. [43] synthesized lactone 72 from hydroxy acid 71 via a mixed sulfonic anhydride. Thus, as shown in Scheme 23, exposure of 71 to p-toluenesulfonyl chloride and triethylamine in benzene followed by chromatography afforded 72 in 52% yield. 

Preparation. This mixed sulfonic-carboxylic anhydride is prepared in quantitative yield by refluxing anhydrous p-toluenesulfonic acid with an excess of acetyl chloride until the evolution of hydrogen chloride ceases (3-5 hrs.) the excess acetyl chloride is removed to give the colorless crystalline anhydride. It can also be prepared from acetic anhydride (excess) and anhydrous p-toluenesulfonic acid. 

Diaryl sulfones. Aryl sulfonyl bromides (but not sulfonyl chlorides) react with silver trifluoromethanesulfonate in nitromethane at 0° to form unstable mixed sulfonic anhydrides (c/ 4, 533-534). These react with arenes (threefold excess) at the same temperature to give diaryl sulfones usually in yields of 80-100%. 

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. 

Muller et al. [30] used the sulfonation of toluene with gaseous SO3 as a reaction to characterize and test a microreactor plant based on a standardized microfluidic platform for laboratory and small-throughput production purposes. The reaction paths during sulfonation of toluene with gaseous SO3 are given in Figure 22.19. Sulfonic acid is the desired product, which is formed via the direct reaction of toluene and SO3 [reaction (23.1)]. In a consecutive reaction, sulfone [reaction (23.2)] is formed, which cannot be converted further. Also, a mixed anhydride and sulfonic... 

Bismuth(III) trifluoromethanesulfonate D3i(OTf)3] has been established as an efficient catalyst (0.05 molar equiv.) for the sulfonylation of a range of substituted benzenes by sulfonyl chlorides and sulfonic anhydrides. With the former, ligand exchange is believed to lead to the formation of a mixed sulfonic anhydride (RS020Tf) which is the reactive sulfonylating species. 

Mixed sulfonic-acetic anhydrides convert ethers to esters. Here the mixed anhydride serves as the source of the acylium ion. 

Amidation. A number of other various amidation reactions have been conducted using BOP. Such preparations include A) O-dimethyl hydroxamates of amino acids and peptides (precursors of chiral peptidyl aldehydes), heterocyclic amide fragments in the synthesis of macrolide and porphyrin models, dan-sylglycine anhydride as a mixed sulfonic-carboxylic imide by dehydration-cyclization of dansylglycine, and selective monoacylation of heterocyclic diamine in carbohydrate series (eq 9). ... 

Fluorosulfuric acid [7789-21-17, HSO F, is a colodess-to-light yellow liquid that fumes strongly in moist air and has a sharp odor. It may be regarded as a mixed anhydride of sulfuric and hydrofluoric acids. Fluorosulfuric acid was first identified and characterized in 1892 (1). It is a strong acid and is employed as a catalyst and chemical reagent in a number of chemical processes, such as alkylation (qv), acylation, polymerization, sulfonation, isomerization, and production of organic fluorosulfates (see Friedel-CRAFTSreactions). 

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. 

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). ... 

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... 

Smith and Stirton applied this mechanism to the sulfonation of long-chain fatty acid esters [31]. Instead of forming the well-defined mixed anhydride during the reaction of fatty acids with S03, the acid esters form a complex less defined in structure and composition. In this complex the a-hydrogen is activated, so that a second molecule of S03 can react. These two addition steps are fast. The final step is again a slow rearrangement of the intermediate with a loss of one molecule of S03. 

In the first step an S03 molecule is inserted into the ester binding and a mixed anhydride of the sulfuric acid (I) is formed. The anhydride is in a very fast equilibrium with its cyclic enol form (II), whose double bonding is attacked by a second molecule of sulfur trioxide in a fast electrophilic addition (III and IV). In the second slower step, the a-sulfonated anhydride is rearranged into the ester sulfonate and releases one molecule of S03, which in turn sulfonates a new molecule of the fatty acid ester. The real sulfonation agent of the acid ester is not the sulfur trioxide but the initially formed sulfonated anhydride. In their detailed analysis of the different steps and intermediates of the sulfonation reaction, Schmid et al. showed that the mechanism presented by Smith and Stirton [31] is the correct one. 

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. 

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 further method for the synthesis of a mixed anhydride between a phosphinic acid and a sulfonic acid employs a sulfonic triazolide ... 

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