Alcohols with /?-toluenesulfonyl chloride

If the temperature is not kept below 25°C during the reaction of primary alcohols with / -toluenesulfonyl chloride in pyridine, it is sometimes observed that the isolated product is not the desired alkyl p-toluenesulfonate but is instead the corresponding alkyl chloride. Suggest a mechanistic explanation for this observation. 

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. 

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... 

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. 

In 1998, Evans published an improved synthesis of bu-box 3 starting from the same amino acid. The updated synthesis began with sodium borohydride-iodine reduction to afford amino alcohol 23 followed again by treatment with dimethyl-malonyl dichloride 24 to afford 25 in 88% yield (from 23). Cyclization was achieved by treatment of 25 with toluenesulfonyl chloride and triethylamine in the presence of a catalytic amount of dimethylaminopyridine to afford bu-box 3 in 82% yield (Fig. 9.6). 

Treatment of the monochloro diethylene glycol 9 with dihydropyran yields the protected alcohol 10. Reaction of 2,2, 2"-triaminotriethylamine (tren) 11 with toluenesulfonyl chloride gives the tritoluenesulfonyl derivative 12. The pyranyl ether 10 may be condensed with the tris(sodium) salt of 12 leading to 13. Removal of the tetrahydropyranyl group is achieved in high yield under... 

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... 

Alcohols react with />-toluenesulfonyl chloride to give useful synthetic intermediates called toluene-sulfonates, or tosylates. The/>-toluenesulfonate ion, a weak base, is an excellent leaving group. Methyl, primary, and secondary tosylates undergo S displacement reactions with nucleophiles. They also react with strong bases in E2 reactions. 

Sulfonate Formation. Treatment of alcohols with mesitylenesulfonyl chloride yields the corresponding sulfonates. Mesitylenesulfonyl chloride is particularly useful for the selective sulfonation of polyhydroxylic systems such as carbohydrates (eq 4). It is more selective than p-Toluenesulfonyl Chloride, which has been frequently used but gives mixtures of products. Unfortunately, the mesitylenesulfonates are not as reactive as the corresponding to-sylates. Numerous 1 -derivatives of sucrose have been synthesized via mesitylenesulfonyl derivatives. ... 

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... 

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. 

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. 

A variant that eliminates the production of water and that has proved effective for esterification of hydroxy and aromatic amino acids involves the use of thionyl chloride instead of acid. At a low temperature, the alcohol reacts with the chloride, generating methyl sulfinyl chloride, which produces the ester, probably through the mixed carboxylic acid-sulfinic acid anhydride (Figure 3.18, B). p-Toluenesulfonyl chloride added to the acid and benzyl alcohol serves the same purpose in the preparation of benzyl esters. 

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. 

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