Alcohols with p-toluenesulfonyl chloride

If the temperature is not kept below 25°C dunng the reaction of primary alcohols with p toluenesulfonyl chloride in pyndine it is sometimes observed that the isolated product is not the desired alkyl p toluenesulfonate but is instead the corresponding alkyl chlonde Suggest a mech anistic explanation for this observation... 

Alkyl chlorides, bromides and iodides can be formed by the reaction of alcohols with p-toluenesulfonyl chloride (or tosyl chloride, abbreviated as TsCl) in the presence of a nitrogen base (e.g. triethylamine or pyridine). The OH group is converted into a tosylate (abbreviated as ROTs), which can be displaced on reaction with CF, BF or I-. The stable tosylate anion is an excellent leaving group (SN1 or SN2 mechanism depending on the nature of the alkyl group, R). 

Tosylates (p-toluenesulfonates) are made by treating alcohols with p-toluenesulfonyl chloride (or tosyl chloride) in the presence of pyridine. A similar reaction (but with a different mechanism, which we will discuss in Chapter 17) with methanesulfonyl chloride (mesyl chloride) gives a mesylate (methanesulfonate). 

Conversion to p toluenesulfonate es ters (Section 8 14) Alcohols react with p toluenesulfonyl chloride to give p toluenesulfonate esters Sulfo nate esters are reactive substrates for nucleophilic substitution and elimma tion reactions The p toluenesulfo nate group is often abbreviated —OTs... 

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... 

When a primary alcohol is treated with p-toluenesulfonyl chloride at room temperature in the presence of an organic base such as pyridine, a tosvlate is formed. When the same reaction is carried out at higher temperature, an alkyl chloride is often formed. Explain. 

Alcohols react with p-toluenesulfonyl chloride (tosyJ chloride, p-TosCl) in pyridine solution to yield alkyl tosylates, ROTos (Section 11.1). Only the 0-H bond of the alcohol is broken in this reaction the C—O bond remains intact, so 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 SN1 and Sjsj2 substitution reactions. 

RC = CCH,X — RCX = C==CH,. /S.y- and 7,S-Acetylenic alcohols can be transformed to the halides in better yields by an alternative procedure, which consists in their esterification with p-toluenesulfonyl chloride and subsequent cleavage of the ester by the action of sodium iodide, lithium chloride, or calcium bromide in an appropriate solvent (60-90%). Halo ethers are prepared by the action of phosphorus tribromide on hydroxy ethers, as in the preparation of /3-ethoxyethyl bromide (66%). In a similar manner, /3-halo esters have been prepared without appreciable dehydration of the /3-hydroxy ester (40-60%). The reaction of cyanohydrins leads to a-halo nitriles. Treatment of 2-nitro-l-propanol with phosphorus pentachloride gives l-chloro-2-nitropropane (47%). ... 

Another potential approach towards 1 was reported by Seido et al. utilizing an asymmetric reduction of the ketone (57 Scheme 15) as the key step. Acylation of the lithium enolate of methyl phenylacetate with the imidazolide, obtained by treatment of the acid 56 with A, V -carbonyldiimidazole, gave the ketoester 57 in 66.4% yield. Asymmetric reduction of 57 with [RuI(/7-cymene)(5)-binap]I, tin chloride, and cam-phor-lO-sulfonic acid in methanol at 80 °C afforded the alcohol 58 as a mixture of syn and anti forms in 87.4% yield. The ratio of syn to anti isomers was 76.3 23.7 and the enantiomeric purity of each form was 95.6% ee and 97.8% ee, respectively. Tosylation of 58 with p-toluenesulfonyl chloride and pyridine in the presence of catalytic amounts of DMAP yielded a diastereomeric mixture of tosylate 59 in 61.8% yield. Deprotection of the /V-Cbz group in 59 by hydrogenation over 5% Pd-C followed by cyclization of the resulting amino tosylate 60 with potassium carbonate in methanol furnished methylphenidate as a mixture of erythro and threo isomers in a 7 3 ratio and 77.5% yield. 

Synthesis from o-threose Synthesis of DABl (1) has been carried out by conversion of the D-threose derivative 33, readily available from D-(—)-diethyl tartrate, to the aminonitrile 34 as an inseparable diastereomeric mixture (Scheme 7). Subsequent deprotection with TBAF gave the alcohol 35 (quantitative). Esterification of 35 with p-toluenesulfonyl chloride afforded 36 (84%), which was treated with TFA-H2O-THF... 

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