transformation of Ketone to Nitrile.

1. TOSMIC
ketone sensitive to MeO- will be destroyed during the reaction. for example beta-ketoester.

2. 1. tosylhydrazine/MeOH to form the hydrazone, then 2. KCN, MeOH, heat.
1. triisopropylbenzylsulfonylhydrazones or trimethylbenzylsulfonylhydrazones have quicker decompose rate than tosylhydrzones. To form the hydrazone, acid (eg. sulfuric acid) usually used to catalyze the reaction. Addition of water can also make the hydrazone formation faster.
2. In the second reaction, acid usually used to make HCN in situ from KCN, which is more reactive.
3. works even for very hindered ketone, for example, ketone with two alpha quaternary carbon center.
4. If temp. goes too high, elimination will happen and you will get an alkene if the ketone has a-hydrogen.

3. reduce the ketone to alcohol, make a leaving group (MsO-),
then treated with NaCN/DMF/water. Sn2 rxn.