Leaving groups tosylates

In general, the reaction can be performed between 0-60°C with the majority of the reactions being run at room temperature. The reactivity of the hydrazones with either the acyl or tosyl leaving group with thionyl chloride depends on the substrate. However, the acylated hydrazones generally provide gaseous by-products where as the tosyl chloride reaction products have to be separated from the reaction mixture. 

As in part (a), identify the nucleophilic anion in each part. The nucleophile replaces the p-toluene-sulfonate (tosylate) leaving group by an SN2 process. The tosylate group is abbreviated as OTs. 

The tosylate leaving group was used in one of the classic experiments that was used to determine the stereochemistry of the SN2 reaction. Now that we know about this leaving group, let s look at the experiment and see how it helped establish that SN2 reactions occur with inversion of configuration. 

Like halides, the tosylate leaving group is displaced by a wide variety of nucleophiles. The Sn2 mechanism (strong nucleophile) is more commonly used in synthetic preparations than the SN1. The following reactions show the generality of SN2 displacements of tosylates. In each case, R must be an unhindered primary or secondary alkyl group if substitution is to predominate over elimination. 

Another method for reducing an alcohol involves converting the alcohol to the tosy-late ester, then using a hydride reducing agent to displace the tosylate leaving group. This reaction works with most primary and secondary alcohols. 

Tlie alcohol was protected as the THP derivative (Chapter 24). Reduction of the acid, via the ester, then allowed introduction of the tosyl leaving group, which was displaced to make an epoxide. The epoxide reacted with a Grignard reagent carrying the diene portion of the target molecule. 

As indicated below, the weakest bases (that is, the anions derived from the strongest acids) are indeed the best leaving groups. The / -toluene-sulfonate (tosylate) leaving group is very easily displaced, as are I" and Br, but Cl" and F" are much less effective as leaving groups. 

A study of glycosidation of 2-Ojacyl-3,4,6-tri-O-benzyl-1-0 -tolylsulfonyl-D-galactopyranose by E. Rachaman (33) has given comparable results and will be reported. However, the use of the tosylate leaving group on fully esterified sugars has not as yet been fully successful and requires further study. 

The yV-alkyl-substituted azadiol was treated with an equimolar amount of tosyl chloride and excess alkali metal hydroxide in an aprotic solvent (powdered NaOH, dioxane, room temperature, 3 hr) to give a 60% yield of the monoaza-crown (Kuo et al., 1978). Template effects are important in this cyclization reaction, so sodium hydroxide was used for aza-15-crown-5 and potassium hydroxide for aza-18-crown-6. The intramolecular ring-closure process is the result of the initial formation of a tosylate by the reaction of one alkoxide anion with tosyl chloride followed by displacement of the tosylate leaving group by the second alkoxide anion. The pure monoaza-crowns were isolated from their metal ion complexes by thermolysis under reduced pressure (Kuo et al., 1980). 

An improvement of the Hdgberg and Cram (1975) procedure to prepare benzomonoaza-crowns using tosylate leaving groups was reported in 1985 and 1986 (Lu and Wu, 1985 Wu and Lu, 1986) (method S-2). The reaction of... 

Fig. 9.4. Left Structure of cyclodecane. The dotted lines show the short H. .. H interactions. Right The cyclodecyl cation intermediate after removal of the tosylate leaving group (see 6)...

Kryptofix 2,2,2 with the diiodide, the ditosylate and the iodotosylate (equation 67), where = 3 or 4. The products were formed in radiochemical yields of between 85 and 95% in 5 minutes. It is interesting that the reaction did not work when = 2 and that the iodide leaving group can be removed exclusively in the presence of the tosylate leaving group. 

You met a related sulfonate anion in the guise of the excellent tosylate leaving group in Chapter 15. 

If you need a reminder about the tosylate leaving group, turn back to p. 349. 

---