Alkoxides reaction with sulfonate esters

Imidazolides of aromatic sulfonic acids react much more slowly in alcoholysis reactions than the carboxylic acid imidazolides. Although the reaction with phenols is quantitative when a melt is heated to 100 °C for several hours, with alcohols under these conditions only very slight alcoholysis is observed. In the presence of 0.05 equivalents (catalytic amount) of sodium ethoxide, imidazole sodium, of NaNH2, however, imidazolides of sulfonic acids react with alcohols almost quantitatively and exothermically at room temperature in a very short time to form sulfonic acid esters (sulfonates). (If the ratio of sulfonic acid imidazolide to alcoholate is 1 2, ethers are formed see Chapter 17). The mechanism of catalysis by base corresponds to that operative in the synthesis of carboxylic esters by the imidazolide method. Because of the more pronounced nucleophilic character of alkoxide ions, sulfonates can also be prepared in good yield by alcoholysis of their imidazolides in the presence of hydroxide ions i.e., with alcoholic sodium hydroxide. 45 Examples of syntheses of sulfonates are presented below. 

When an alkoxide ion is used as the nucleophile, the reaction is called a Williamson ether synthesis. Because the basicity of an alkoxide ion is comparable to that of hydroxide ion, much of the discussion about the use of hydroxide as a nucleophile also applies here. Thus, alkoxide ions react by the SN2 mechanism and are subject to the usual Sn2 limitations. They give good yields with primary alkyl halides and sulfonate esters but are usually not used with secondary and tertiary substrates because elimination reactions predominate. 

The resistance of the furoxan ring to chemical attack allows derivatives to be prepared via the reactions of the substituents (Section 4.22.3.4). Carboxylic acids are available by permanganate oxidation of methyl derivatives or by hydrolysis of the corresponding esters reaction with ammonia affords carboxamides. Acylfuroxans provide a source of hydroxyalkyl compounds by reduction, and oximes, for example, via nucleophilic addition. Acylation and oxidation of aminofuroxans allows the amide and nitro derivatives to be prepared. Nucleophilic displacements of nitro substituents can take place, but can be somewhat hazardous on account of the explosive nature of these compounds. Alkoxy derivatives are formed with sodium alkoxide, while reaction with thiolate anions yields sulfides, from which sulfones can be synthesized by peracid oxidation. Nitrofuroxans have also been reduced to... 

The most interesting behavior of the three dianhydrides is found in the displacement reactions of their 0-sulfonyl derivatives, and at present it seems that the reported results may be covered by three general rules. (1) Displacement of sulfonyloxy groups from the 0-sulfonates may be achieved under certain conditions, and occurs with inversion of configuration at the point of displacement. (2) Ammonia and halide ions displace sulfonyloxy groups, but alkali hydroxides (and perhaps alkoxides) merely hydrolyze the sulfonate esters by 0-sulfonyl fission, with retention of configuration. (3) Displacements by halide ions are possible only for endo sulfonyloxy groups. These rules are only tentative, and may be modified when more sulfonyloxy compounds, and their behavior to a wider variety of anions, have been studied. 

Alkyl phenyl sulfones (piCj,27) are nearly as acidic as esters hence they are readily deprotonated by n-BuLi, LDA in THF, or EtMgBr in THF to give a-metalated sulfones. Their reaction with aldehydes gives a mixture of diastereomeric P-phenylsul-fone alkoxide adducts. Reductive elimination of the benzenesulfinate moiety from the adduct to produce the alkene is usually slow. To minimize side reactions, the hydroxyl group is first converted to an acetate, benzoate, mesylate, or /7-toluenesul-fonate and then treated with an excess of sodium amalgam [Na(Hg), prepared by adding small pieces of sodium to mercury] in methanol to furnish the trans-dlk n P... 

Aliphatic alcohols can also be converted into their ethers by /7-toluene-sulfonic esters. For this purpose, either the anhydrous alcohol is treated with the amount of sodium necessary for formation of the alkoxide or the corresponding amount of alkali hydroxide is dissolved in an excess of the alcohol, and the resulting mixture is brought into reaction with the /7-toluenesulfonic ester. Yields are about 70-80% by both methods. When the costly higher aliphatic alcohols are in question the sodium alkoxide is prepared in benzene, and that mixture is treated at the boiling point with the sulfonic ester. 

The reaction of alkoxide ions with alkynyliodonium salts is unproductive, leading to only decomposition products rather than the desired alkoxyacetylenes. Similarly, reaction of R3SiO does not lead to any siloxyalkynes. In contrast the softer sulfonate, carboxylate, and phosphate nucleophiles all readily react with alkynyliodonium salts leading to the corresponding alkynyl sulfonate, carboxylate and phosphate esters [4]. 

Williamson ether synthesis Sm2 reaction of an alkoxide with a primary haloalkanc or sulfonate ester, yielding an ether. 

In Chapter 11, several different nucleophiles reacted with alkyl halides or sulfonate esters via both S l and Sn2 conditions. Alkoxides (RO ) are important nucleophiles, and the 8 2 reaction of an alkoxide with an alkyl halide was the basis of the Williamson ether synthesis in Chapter 11, Section 11.3.2. Based on the poor reactivity of tertiary halides with nucleophiles in the 8 2 reaction, reading Chapter 11 may lead to the conclusion that an alkoxide such as sodium ethoxide will give no reaction when mixed with a tertiary halide. This is incorrect. A reaction that forms the basis of this chapter occurs because alkoxides such as sodium ethoxide are strong bases as well as nucleophiles. 

Sulfonate ester NALGs are prepared via a DMAP-catalyzed addition of alcohols to 2-(2-methoxyethoxy)-ethyl 2-(chlorosulfonyl) benzoate (eq 2). For more hindered cases, the alcohol was first converted to the sodium alkoxide using NaH followed by the addition of 2-(2-methoxyethoxy)-ethyl 2-(chlorosulfonyl) benzoate. For the most hindered alcohols, both DMAP and NaH were used to give the sulfonate product (NALG) in good yields (80-95%) with shorter reaction times. In all cases, sulfonate NALGs were exceptionally stable to aqueous workup and silica gel chromatography. ... 

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