P-Toluenesulfonyl s. a. Tosyl

Problem 13.18 (a) Why are sulfonate esters such as p-toluenesulfonyl (tosyl) esters widely used in S 2 reactions (b) How is this reaction used for indirect displacement of —OH from ROH ... 

Alcohols react with p-toluenesulfonyl chloride (tosyl chloride, jo-TosCl) in pyridine solution to yield alkyl tosylates, ROTos (Section 11.2). Only the 0-H bond of the alcohol is broken in this reaction the C-O bond remains intact, and no change of configuration occurs if the oxygen is attached to a chirality center. The resultant alkyl tosylates behave much like alkyl halides, undergoing both S>jl and 8 2 substitution reactions. 

S. 4-Aaetylpyridine oxime toaylate. Pure E-oxime (27.1 g, 0.20 mol) and p-toluenesulfonyl chloride (47.9 g, 0.22 mol) (Note 6) are added to 100 mL of anhydrous pyridine (Note 7) in a 1-L, round-bottomed flask fitted with a drying tube and a large magnetic stirring bar. The reaction mixture is stirred at 25°C for 24 hr a precipitate of pyridine hydrochloride forms. A 500-mL portion of ice water is added with continued stirring. The initial precipitate dissolves and a voluminous white precipitate soon forms. This is collected by suction filtration, washed with three 150-raL portions of cold water and dried under reduced pressure and over Drierite to constant weight. The yield of pure tosylate, mp 79-81°C (Note 8), is 55.1 g (95%). 

Glycosidic or allylic alcohols (even when s-) can be converted in a 80-95% yield to alkyl chlorides by means of p-Toluenesulfonyl Chhride-TiMAP. Simply primary alcohols react slower and secondary ones are converted to tosylates. ... 

Tosyl chloride added to a stirred soln. of p-nitraniline in pyridine, and heated 30 min. on a steam bath under anhydrous conditions N-(p-nitrophenyl)-p-toluenesulfonamide (Y 95%) dissolved in dimethyl sulfoxide, treated with K-carbonate and 1,3-dibromopropane, stirred 5 days at room temp. N-(3-bromopropyl)-N-(p-nitrophenyl)-p-toluenesulfonamide (Y 80%) added to a mixture of ethyl acetoacetate, a 53.5%-dispersion of NaH in mineral oil, and ferf-butanol (previously warmed with stirring under anhydrous conditions until the NaH has dissolved and Hg-evolution ceased), refluxed 20 hrs. with stirring, and the resulting crude ethyl 2-acetyl-5-p-nitranilino)-N-(p-toluenesulfonyl)-valerate refluxed 48 hrs. with guanidine carbonate in ferf-butanol 2-amino-6-methyl-5- [ (N-p-toluenesulfonyl-p-nitranilino) propyl] -4-pyrimidinoI (Y 69%). F. e. s. B. R. Baker, D. V. Santi, and H. S. Shapiro, J. Pharm. Sci. 53, 1317 (1964). 

For example, the treatment of cw-S-methylcyclohexanol with p-toluenesulfonyl chloride and pyridine forms a cis tosylate A, which undergoes backside attack by the nucleophile "OCH3 to yield the trans ether B. 

Bromo-N -dimethyladenosine and di-n-butyltin oxide refluxed 1 hr. in methanol 2, 3 -0-dibutylstannylene-8-bromo-N -dimethyladenosine (Y 90%) suspended in methanol, triethylamine and p-toluenesulfonyl chloride added, and stirred 18 hrs. at room temp. 2 -0-tosyl-8-bromo-N -dimethyladenosine (Y 81%). M. Ikehara and T. Maruyama, J. Carbohyd. Nucleos. Nucleot. 2, 335 (1975) preferential 2-acylation of carbohydrates s. a. R. M. Munavu and H. H. Szmant, J. Org. Chem. 41, 1832 (1976) preferential protection of carbohydrate hydroxyl by acylation or alkylation cf. M. A.Nashed and L. Anderson, Tetrah. Let. 1976, 3503. 

NaH-dispersion followed by purified p-toluenesulfonyl chloride added with ice-cooling to a soln. of 2-nitro-3,4,5-trimethoxybenzyl alcohol in anhydrous benzene, and stirred 13 hrs. at room temp. -> 2-nitro-3,4,5-trimethoxybenzyl tosylate. Y 90-94%.— Tosylation in pyridine was not successful. K. I. H. Williams, D. S. Tarbell et al.. Am. Soc. 82, 3982 (1960). 

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