Tosylations alcohols, / -toluenesulfonyl chloride

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. 

Alcohol p-Toluenesulfonyl chloride Alkyl p-toluenesulfonate (alkyl tosylate)... 

The hydroxyl group of an alcohol is a poor leaving group and so sulfonation by treatment with the appropriate sulfonyl chloride provides a valuable method of activating the hydroxyl group towards nucleophilic substitution. The tosylate derivatives (17, R = / -MeCeH4) obtained by treatment of the alcohol with / -toluenesulfonyl chloride (tosyl chloride) in pyridine are widely used for the activation of the hydroxyl group. 

Alternatively, an alcohol can be made more reactive toward nucleophilic substitution by treating it with p ra-toluenesulfonyl chloride to form a tosylate. As noted on several previous occasions, tosylates are even more reactive than halides in nucleophilic substitutions. Note that tosylate formation does not change the configuration of the oxygen-bearing carbon because the C-0 bond is not broken. 

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. 

Axenrod and co-workers reported a synthesis of TNAZ (18) starting from 3-amino-l,2-propanediol (28). Treatment of (28) with two equivalents of p-toluenesulfonyl chloride in the presence of pyridine yields the ditosylate (29), which on further protection as a TBS derivative, followed by treatment with lithium hydride in THF, induces ring closure to the azetidine (31) in excellent yield. Removal of the TBS protecting group from (31) with acetic acid at elevated temperature is followed by oxidation of the alcohol (32) to the ketone (33). Treatment of the ketone (33) with hydroxylamine hydrochloride in aqueous sodium acetate yields the oxime (34). The synthesis of TNAZ (18) is completed on treatment of the oxime (34) with pure nitric acid in methylene chloride, a reaction leading to oxidation-nitration of the oxime group to em-dinitro functionality and nitrolysis of the A-tosyl bond. This synthesis provides TNAZ in yields of 17-21 % over the seven steps. 

Compound A is the p-toluenesulfonate ester (tosylate) of /ran.v-4-/cr/-butylcyciohexanol. The oxygen atom of the alcohol attacks the sulfur of p-toluenesulfonyl chloride, and so the reaction proceeds with retention of configuration. 

At lower temperatures, a tosylate is formed from the reaction of p-toluenesulfonyl chloride and an alcohol. The new bond is formed between the toluenesulfonyl group and the oxygen of the alcohol. At higher temperatures, the chloride anion can displace the -OTos group, which is an excellent leaving group, to form an organochloride. 

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

Sulfur example—formation of a tosylate from toluenesulfonyl chloride and an alcohol ... 

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. 

When methanesulfonyl chloride was allowed to react with 2,3,4,6-tetra-O-ben-zylglucopyranose and collidine in dichloromethane, the a-glucopyranosyl chloride was isolated regardless of whether the quaternary ammonium bromide was included. Addition of methanol to the reaction mixture resulted in the formation of an anomeric mixtiue of methyl glycosides. Similar results were obtained with toluenesulfonyl chloride, although it was noted that the initial sulfonylation was somewhat slower [8,9]. The use of tosyl chloride in the dehydrative coupling of alcohols with pyranoses was later revisited by Szeja and his coworkers, with the difference that aqueous... 

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). 

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