Sulfonate esters from alcohols + sulfonyl chlorides

A primary or secondary amine attacks a sulfonyl chloride and displaces chloride ion to give an amide. Amides of sulfonic acids are called sulfonamides. This reaction is similar to the formation of a sulfonate ester from a sulfonyl chloride (such as tosyl chloride) and an alcohol (Section 11-5). 

Section 7.8). Other classes of derivatives are thus most conveniently prepared from the sulfonyl chloride. Reaction with an alcohol leads to formation of a sulfonate ester. Two common sulfonyl chloride reagents employed to make sulfonate esters from alcohols arep-toluenesulfonyl chloride, known as tosyl chloride, and methanesulfonyl chloride, known as mesyl chloride (see Section 6.1.4). Note the nomenclature tosyl and mesyl for these groups, which may be abbreviated to Ts and Ms respectively. 

The reaction of alcohols with acyl chlorides is analogous to their reaction with p toluenesulfonyl chloride described earlier (Section 8 14 and Table 15 2) In those reactions a p toluene sulfonate ester was formed by displacement of chloride from the sulfonyl group by the oxygen of the alcohol Carboxylic esters arise by displacement of chlonde from a carbonyl group by the alcohol oxygen... 

Mannitol hexanitrate is obtained by nitration of mannitol with mixed nitric and sulfuric acids. Similarly, nitration of sorbitol using mixed acid produces the hexanitrate when the reaction is conducted at 0—3°C and at —10 to —75°C, the main product is sorbitol pentanitrate (117). Xylitol, ribitol, and L-arabinitol are converted to the pentanitrates by fuming nitric acid and acetic anhydride (118). Phosphate esters of sugar alcohols are obtained by the action of phosphorus oxychloride (119) and by alcoholysis of organic phosphates (120). The 1,6-dibenzene sulfonate of D-mannitol is obtained by the action of benzene sulfonyl chloride in pyridine at 0°C (121). To obtain 1,6-dimethanesulfonyl-D-mannitol free from anhydrides and other by-products, after similar sulfonation with methane sulfonyl chloride and pyridine the remaining hydroxyl groups are acetylated with acetic anhydride and the insoluble acetyl derivative is separated, followed by deacetylation with hydrogen chloride in methanol (122). Alkyl sulfate esters of polyhydric alcohols result from the action of sulfur trioxide—trialkyl phosphates as in the reaction of sorbitol at 34—40°C with sulfur trioxide—triethyl phosphate to form sorbitol hexa(ethylsulfate) (123). 

Halogeno saccharides can be prepared by the displacement of a sulfonate ester with a halogen ion. Primary fluorides, bromides, chlorides and iodides can be prepared from mesylates (R0S02CH3) and tosylates (R0S02PhMe) (Scheme 3.3a).12 The latter derivatives can be obtained cheaply by treatment of alcohols with a sulfonyl chloride in pyridine or triethylamine. 

Esters of aliphatic and aromatic sulfonic acids are conveniently prepared in high yields from alcohols and sulfonyl halides. A basic medium is required. By substituting sodium butoxide for sodium hydroxide in butanol, the yield of n-butyl p-toluenesulfonate is increased from 54% to 98%. Ethyl benzenesulfonate and nuclear-substituted derivatives carrying bromo, methoxyl, and nirro groups are prepared from the corresponding sulfonyl chlorides by treatment with sodium ethoxide in absolute ethanol the yields are 74-81%. Pyridine is by far the most popular basic medium for this reaction. Alcohols (C -Cjj) react at 0-10° in 80-90% yields, and various phenols can be converted to aryl sulfonates in this base. "... 

Sulfonate ester, formation from sulfonyl chloride and alcohol, 67, 78, 84, 145 Sulfonation, benzoic acid, 269 phenol, 104 o-xylene, 47... 

Many of the reagents that are used to activate alcohols toward nucleophilic substitution (e.g., SOCI2, PCI3) cannot be used to activate ethers. When an alcohol reacts with an activating agent such as a sulfonyl chloride, a proton dissociates from the intermediate in the second step of the reaction and a stable sulfonate ester results. 

The most familiar of the sulfonic adds derived from camphor is 10-camphorsulfonic add (44, Reychler s acid45). Both enantiomers are commercially available and convenient procedures exist for their preparation by sulfonation of camphor (ref 46 exemplifies the racemate, but the procedure works equally well for optically active camphor). The free acid is often applied to the resolution of basic compounds such as amines. A detailed review on the use of derivatives of this acid as auxiliaries has been given3. Esters of this add are normally obtained by the reaction of the alcohols with the sulfonyl chloride which is also commerdally available (or readily obtained by the reaction of the free acid with phosphorus pentachloride or thionyl chloride46,48). Such esters with unsaturated alcohols have been used for diastereoselective [1,2] sigma tropic rearrangements (Section D.1.6.3.3.). Allyl esters have been used for enantioselective alkylation reactions, in which camphorsulfonic acid reacts as the chiral leaving group (Section D.1.1.2.2.). 

The second concealed ElcB elimination is disguised in the mechanism of formation of methanesulfonates (mesylates). When we introduced sulfonate esters in Chapter IS, and revisited them on p. 391 of this chapter, we avoided (uncharacteristically, you may say) explaining the mechanism by which they are formed from sulfonyl chlorides. This was deliberate because, while TsCl reacts with alcohols by the mechanism you might predict, the reaction with MsCl involves an elimination step. 

The structure and nomenclature of sulfonate esters (see 113, 114, or 115) are described in Chapter 20 (Section 20.11.2). It is also true that sulfonate esters are good leaving groups in the substitution reactions described in this chapter (see Section 11.2.4). Sulfonate esters are prepared by the reaction of sulfonic acids with alcohols—much the way that carboxylic acid esters are prepared from carboxylic acids and alcohols (described in Chapter 20, Section 20.11.2). More commonly, sulfonate esters are prepared by the reaction of a sulfonyl chloride (see 112) with an alcohol. This reaction is also described in Chapter 20. This section presents only a simple preview of that chemistry, with the goal of showing that it is easy to convert alcohols into sulfonate esters, which are then useful as leaving groups in substitution reactions. The formal mechanism of these reactions will be discussed in Chapter 20. 

Esters are prepared from carboxylic acids by the reaction between an acid chloride and an alcohol or between a carboxylic acid and an alcohol under acidic conditions. Both sulfonic acids and sulfonyl chlorides react with alcohols to form sulfonate esters. When butanesulfonyl chloride (177) reacts with propanol, usually in the presence of a base such as triethylamine, propyl butanesulfonate (180) is formed. A wide range of sulfonyl esters can be formed this way from an alcohol and a sulfonic acid. 

CHAPTER 7 Sequential Syntheses The Transition from Macro to Micro 7-61. Sulfonyl chlorides also react readily with alcohols to yield sulfonate esters ... 

Several sulfonyl chlorides are available to activate OH groups. The most common one is para-toluenesulfonyl chloride (abbreviated as TsCl). The sulfonate ester formed from the reaction of TsCl and an alcohol is called an alkyl tosylate (abbreviated as ROTs). 

The inorganic esters in the reactions of SOCI2 are special examples of leaving groups derived from sulfur-based acids. They are related to the sulfonates (Section 6-7). Alkyl sulfonates contain excellent leaving groups and can be readily prepared from the corresponding sulfonyl chlorides and an alcohol. A mild base such as pyridine or a tertiary amine is often added to remove the HCl formed. 

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