Before the preparation, sodium azide 10.98g (168.9mmol) was powdered with a spatula and dried in a 0.5L round flask on 80C oil bath on highvac (0.25 Torr) for 90 min. The cooled flask was flushed with Ar, trityl chloride 31.19g (111.0mmol) and anhydrous acetonitrile (about 100mL) was added and the mixture was vigorously stirred at 80C for 4 hours. The reaction mixture was cooled to ambient temperature, the salts were removed by filtration and washed thoroughly with toluene. The combined filtrates were evaporated, the residue was dissolved in hexane 100mL and filtered through a pad of silica 50g. The silica pad was washed with additional hexane 100mL and then with 200mL of 1:1 hexane-dichloromethane mixture. The combined filtrates were evaporated, the residue was dissolved in pentane 100mL. The solution was seeded with a sample of crystalline material*, allowed to crystallize at RT for 1 hour and then in a fridge overnight (+4C, 8 hours). The supernatants were quickly decanted, the crystalline mass in the flask (27.051g) was rinsed with chilled pentane (2x10mL) and then dried on highvac. Evaporating the supernatants and re-crystallizing the residue from pentane (20mL, +4C) provided additional 3.701g of a pure product. The combined yield was 30.752g (97%) of large shiny pale yellow crystals.
1H(d6-DMSO, 400MHz): 7.408(m, 9H), 7.255(m, 6H); 13C(d6-DMSO, 100MHz): 142.48(3C), 128.44(6C), 127.88(9C), 76.98(1C)
Hexane works for crystallization as well. *A simple way to obtain seeds for crystallisation is to dry a small sample of the oily product on highvac, then let it sit in an open flask for a day or two.
The reaction can also be run in toluene if 5mol% of Bu4NBr is added as solid phase transfer and the azide is powdered thoroughly. Toluene may be a better solvent for process scale-up (the reaction mix can be directly filtered through silica pad, the solvents are not mixed, etc) but the reaction takes longer to complete and evaporating large volumes of toluene is not fun. Running the reaction in acetonitrile is preferable on lab scale.
Mtr-N3 can be made in the same way from p-methoxytrityl chloride, in nearly quantitative yield as a pale yellow oil.
Trityl azide is easy to work with – it forms gorgeous crystals, is not impact-sensitive and its decomposition occurs well above boiling point of toluene (110C). But it is rather unreactive azide – I tried to use it for making trityl triazoles and the Cu(I)-catalyzed cyclizations did not work on monoaryl alkynes.