Alcohol to Tosylate using Tosyl Cl, base

Reaction, Reagents
& Mechanism

Reaction & Reagents info

  • OH– ion (hydroxide ion), as such, is a poor leaving group, as it is quite strong base. However, OH group shall be converted to a better leaving group such as OMs, OTs or OTf groups for further useful organic conversion

Sulfonates as better leaving groups

  • Leaving group ability; OTf > OTs > OMs

Other ways of synthesizing better leaving groups for SN2 reactions:

Stereochemical outcome of sulfonate ester (OMs, OTs and OTf):

  • Alkyl sulfonates undergo SN2 and E2 reaction in a manner identical to that of alkyl halides

(a) Substitution:

(b) Elimination:


For review papers and other articles, 
refer to the tab "References"

Useful Links on Reagent & Reaction:

Mechanism

Additional details

Scheme & Procedure

General Procedure:

To a solution of alcohol (1 eq.) in dry DCM (10 Vol) at 0 oC was added pyridine (or) triethylamine (1.5 eq.) followed by p-toluenesulfonyl chloride (1.2 eq.) and stirred at 0 oC for 4 h (If the reaction does not proceed, it shall be brought to room temperature and stirred for 2 h). The reaction is monitored by TLC. After the completion of the reaction, the reaction mixture is diluted with water and layers separated. The aqueous layer is extracted with DCM. The organic layer is then successively washed with water (10 Vol x 2) and brine solution, dried over sodium sulphate, filtered and concentrated under reduced pressure to get the desired compound.

Note:

  • The preferable solvents are DCM. THF and toluene shall also be used.
  • If the alcohol is not reactive, in place of py or Et3N, n-BuLi or NaH shall be used to generate the anion.

Typical Procedure:

Patent references

Scale-up &
Green Chem.

Tosylates have been synthesized on large-scale and they are key intermediates in the manufacturing of pharmaceutical intermediates

Scale-Up Typical Procedure:

Green Chemistry Aspects:

Reaction Tree

References

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