Tosylamide-based cyclisations

The toluenesulfonyl group in these reactions is also a protecting group for nitrogen, for example in 3, but it must be removed subsequently to liberate the free secondary amine. There are various methods for achieving this deprotection step which are compatible with ether linkages. The two most useful involve either the use of hydrogen bromide in acetic acid in the 

Caution Carry out all procedures in a well-ventilated hood, and wear disposable vinyl or latex gloves and chemical-resistant safety goggles. 

The following procedure is representative of a direct [1+1] cyclisation reaction using a toluenesulfonamide at medium dilution.3 

Take a block of sodium metal out of the oil and with a sharp knife cut approximately 1 g from it. Wash the block carefully with dry hexane (in a small beaker) to remove adhering oil, and cut the block into three smaller pieces. Dry the shiny blocks with filter papers and weigh out 0.92 g accurately. 

Carefully add the sodium metal (0.92 g, 40 mmol) to a single-necked round-bottomed flask (250 mL) containing dry methanol (120 mL), maintained under an atmosphere of nitrogen. Attach a water-cooled condenser equipped with a nitrogen inlet, and gently heat (40°C) and stir (Teflon stirrer bar) the mixture until all of the sodium has dissolved. 

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