Methanesulfonyl Azide

MeSO2N3

[1516-70-7]  · CH3N3O2S  · Methanesulfonyl Azide  · (MW 121.14)

(diazo transfer reagent for activated methylene,1 methine,1,2 and methyl3 groups; functionalization of double and triple bonds)

Alternate Name: mesyl azide.

Physical Data: mp 18-20 °C; bp 44-45 °C/1 mmHg; n20D 1.4675; d204 1.4361 g cm-3.

Solubility: sol Et2O, MeOH, MeCN; sparingly sol 95% EtOH, cold H2O.

Form Supplied in: low-melting white solid or clear, colorless oil.

Analysis of Reagent Purity: IR, NMR, refractive index.

Preparative Methods: reaction of Methanesulfonyl Chloride with Sodium Azide in MeOH(EtOH)/H2O1,3 or acetone2 (55-61 or 96% yields, respectively). By substituting acetone for methanol, the formation of MeSO2OMe is avoided and the reagent is obtained in >95% purity.2

Purification: crystallization from ether in dry-ice/acetone or from 95% EtOH at -75 °C; distillation in vacuo.

Handling, Storage, and Precautions: should be stored in the cold and the dark. Explosive when heated above 130 °C. No experimentalists have reported any difficulty handling MsN3, but proper caution should be used, as with all azide reagents. Use in a fume hood.

Diazo Transfer Reagent.

Methanesulfonyl azide (MsN3) is claimed to be a superior reagent1,2 for diazo transfer reactions.4 It is useful for both of the main strategies for accomplishing this process: (a) direct transfer of the diazo function to activated methylene groups; and (b) transfer to the methine position of a-acyl carbonyl substrates with a subsequent cleavage of the acyl group.

Direct transfer with MsN3 has been reported for alkyl-,1a aryl-,5a and alkynyl-substituted (eq 1)6 3-keto esters, N,N-disubstituted acetoacetamides,5b derivatives of malonic acid,7 and 2,4-pyrrolidinediones,8 and for alkynyl-substituted phenylsulfonyl acetates,6 to give corresponding diazo dicarbonyl or diazo carbonylsulfonyl compounds in high yields. The process is usually realized with Triethylamine as the base,4 or in the presence of sodium acetate.5a

A very rare diazo transfer onto a methyl group is shown in eq 2.3 Reaction of oxime ethers with 1 equiv of n-Butyllithium followed by addition of MsN3 to the enolate affords pure 2-diazo oxime ethers.

The deformylation and deacetylation strategy using MsN3 is an efficient route to numerous saturated,1,5 alkynyl-substituted,6 and chiral 2-diazo esters5,9 and 2-diazo ketones.2,6 Substituting trifluoroacetylation of lithium enolates for the usual Claisen formylation step4 can be used to prepare unsaturated cyclic and acyclic 2-diazo ketones via a-trifluoroacetyl ketones (eq 3).2

Significant regioselectivity can be achieved in this process when Lithium Diisopropylamide or Lithium 2,2,6,6-Tetramethylpiperidide (LTMP) is employed for generation of the enolate from 2-octanone (eq 4).2

1,3-Dipole.

Cycloaddition reactions of MsN3 with activated triple bonds of alkoxyalkynes10 and alkynylamines11 give rise to substituted 1,2,3-triazoles (>85%)11c or their open-chain diazo isomers (54-96%). The particularly nucleophilic double bonds of 5-alkylidenedihydrotetrazoles react with mesyl azide to produce stable zwitterions or iminotetrazines, after elimination of N2 and a 1,2-shift of a nitrogen atom in a postulated intermediate triazoline (eq 5).12

Regioselective formation of a-piperidone imines,13 a-imino ethers,14 and aziridines15 occurs almost quantitatively in MsN3 cycloadditions with the nucleophilic double bonds of tetrahydro- and dihydropyridines, vinyl ethers, and diazanorbornadiene. A tendency towards a-imino ether formation decreases in the order N3SO2Me > N3CO2Me > N3Ph.14 Isolation of tetracyclic azetidines from cycloaddition reactions of MsN3 with 7-substituted norbornadienes has also been reported.16

Imination Agent and Nitrene Radical Precursor.

The imination of Triphenylphosphine17 and other trivalent phosphorus compounds18 (Staudinger reaction19) with MsN3 gives iminophosphoranes in good yields (eq 6).18a A related triphenylarsine imine, Ph3As=NSO2Me, is formed by Cu-catalyzed decomposition of MsN3 at 110 °C in the presence of Triphenylarsine (74% yield).20

Efficient reduction of mesyl azide to the sulfonamide by hydrogen abstraction from the surrounding medium occurs on photolysis in isopropyl alcohol21 and a few other solvents.22 However, methanesulfonylnitrene and the species generated by the photolysis or thermolysis of MsN3 in hydrocarbons, aromatic, and other substrates are usually relatively unselective reagents.23


1. (a) Taber, D. F.; Ruckle, R. E.; Hennessy, M. J. JOC 1986, 51, 4077. (b) Taber, D. F.; Hennessy, M. J.; Lovey, J. P. JOC 1992, 57, 436.
2. Danheiser, R. L.; Miller, R. F.; Brisbois, R. G.; Park, S. Z. JOC 1990, 55, 1959.
3. Shatzmiller, S.; Bercovici, S. LA 1992, 877.
4. Regitz, M.; Maas, G. Diazo Compounds; Academic: New York, 1986; pp 326-435.
5. (a) Doyle, M. P.; Bagheri, V.; Wandless, T. J.; Harn, N. K.; Brinker, D. A.; Eagle, C. T.; Loh, K.-L. JACS 1990, 112, 1906. (b) Doyle, M. P.; Shanklin, M. S.; Pho, H. Q.; Mahapatro, S. N. JOC 1988, 53, 1017.
6. (a) Padwa, A.; Kinder, F. R. JOC 1993, 58, 21. (b) Kinder, F. R.; Padwa, A. TL 1990, 31, 6835.
7. Lowe, G.; Ramsay, M. V. J. JCS(P1) 1973, 479.
8. (a) Stork, G.; Szajewski, R. P. JACS 1974, 96, 5787. (b) Lowe, G.; Ridley, D. D. CC 1973, 328.
9. Doyle, M. P.; Protopopova, M. N.; Brandes, B. D.; Davies, H. M. L.; Huby, N. J. S.; Whitesell, J. K. SL 1993, 151.
10. Himbert, G.; Regitz, M. CB 1972, 105, 2975.
11. (a) Himbert, G.; Regitz, M. CB 1972, 105, 2963. (b) Himbert, G.; Regitz, M. CB 1974, 107, 2513. (c) Himbert, G.; Regitz, M. LA 1973, 1505.
12. (a) Quast, H.; Regnat, D.; Peters, E.-M.; Peters, K.; Schnering, H. G. AG(E) 1990, 29, 695. (b) Quast, H.; Regnat, D.; Balhtasar, J.; Banert, K.; Peters, E.-M.; Peters, K.; Schnering, H. G. LA 1991, 409.
13. Warren, B. K.; Knaus, E. E. JHC 1987, 24, 1413.
14. Migita, T.; Hongoh, K.; Naka, H.; Nakaido, S.; Kosugi, M. BCJ 1988, 61, 931.
15. (a) Warren, B. K.; Knaus, E. E. JMC 1981, 24, 462. (b) Ondrus, T. A.; Knaus, E. E.; Giam, C. S. CJC 1979, 57, 2342. (c) Stout, D. M.; Takaya, T.; Meyers, A. I. JOC 1975, 40, 563.
16. Huda, E.; Martin, H.-D.; Mayer, B.; Somnitz, K.-M.; Steigel, A.; Haddad, H.; Distefano, G.; Modelli, A. CB 1991, 124, 2879.
17. Horner, L.; Christmann, A. CB 1963, 96, 388.
18. (a) Heydt, H.; Regitz, M. LA 1977, 1766. (b) Kabachnik, M. I.; Gilyarov, V. A. IZV 1961, 819. (c) Goldstein, J. A. JOC 1977, 42, 2466.
19. Staudinger, H.; Meyer, J. HCA 1919, 2, 635.
20. Cadogan, J. I. G.; Gosney, I. JCS(P1) 1974, 460.
21. Reagan, M. T.; Nickon, A. JACS 1968, 90, 4096.
22. Abramovitch, R. A.; Knaus, G. N. CC 1974, 238.
23. (a) Torimoto, N.; Shingaki, T.; Nagai, T. JOC 1978, 43, 631. (b) Shingaki, T.; Inagaki, M.; Torimoto, N.; Takebayashi, M. CL 1972, 1181. (c) Abramovitch, R. A.; Knaus, G. N., Uma, V. JOC 1974, 39, 1101. (d) Abramovitch, R. A.; Roy, J.; Uma, V. CJC 1965, 43, 3407. (e) Breslow, D. S.; Edwards, E. I., Linsay, E. C.; Omura, H. JACS 1976, 98, 4268.

Valerij A. Nikolaev

St. Petersburg State University, Russia



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