(X = Cl)

[4460-46-2]  · C7H5ClN2  · 3-Chloro-3-phenyldiazirine  · (MW 152.58) (X = Br)

[4222-25-7]  · C7H5BrN2  · 3-Chloro-3-phenyldiazirine  · (MW 191.99)

(stable cyclic isomer of chlorodiazomethane; excellent source of chlorocarbene following thermolysis or photolysis2)

Physical Data: colorless liquid; bp 33-35 °C/0.5 mmHg; IR N=N stretch 1560 cm-1; UV l = 388 nm.

Solubility: sol hydrocarbons, diethyl ether, ethyl acetate, and acetonitrile

Preparative Methods: by treatment of benzamidine hydrochloride with NaOCl (eq 1).

Handling, Storage, and Precautions: can be stored in the dark at 0-10 °C for several weeks under Ar without decomposition; solutions of the reagent have not been known to detonate, although more volatile chlorodiazirines, e.g. methylchlorodiazirine, are prone to explosion3 and are shock sensitive; explosions have occurred on warming to rt after storage at 77 K. Extreme care is required during cold trap procedures when solid diazirine is present; in GC, diazirine must never be injected neat (the high temperature at the injector block will lead to an explosion). Always take precautions (e.g. safety shields) when working with diazirines.

Diazirines are cyclic isomers of diazoalkanes. The chemistry of diazirines has a relatively short history, dating from the discovery of these compounds in 1960 by Paulsen,4 and Schmitz and Ohme.5 The increasing interest and the progress in this field have encouraged continuous reviews.6 In 1965, Graham's pioneering paper described the synthesis of 3-chloro-3-phenyldiazirine.1b The mechanism for hypochlorite oxidation of amidines (with diazirine formation) has been reviewed.7,8

Reactions of Diazirines.

The reaction of phenylchlorodiazirine with Phenyllithium (eq 2) yields diphenylbenzamidine, whereas the reaction with Methyllithium gives acetophenone.1d

Another facet of halodiazirine chemistry is the reaction with nucleophiles7,8 and this is illustrated by the reaction of phenylbromodiazirine with the nucleophiles methoxide, fluoride, and cyanide ions (eq 3).

Synthetically, the exchange reaction has been used to prepare methoxy-substituted methylenecyclopropanes (eq 4).8

An exchange reaction of phenylbromodiazirine with N-methylethanolamine affords diazirine, which yields the carbene upon loss of nitrogen. The oxazolidine product is formed by the intramolecular O-H insertion of the carbene (eq 5).9

Reactions of Carbenes.

Chlorodiazirine compounds are remarkably stable in the presence of organic and inorganic reagents, in sharp contrast to the behavior of their linear isomers, which can only be detected by isolation matrix techniques.10 Because of their stability, chlorodiazirines have been investigated as a source of chlorocarbenes following thermolysis, photolysis,2 or ultrasound.11 Thermal decomposition of phenylchlorodiazirine in cyclohexene gives a mixture of exo- and endo-7-chloronorcaranes.1b,12 Thus chlorodiazirines have played an essential role in the development of singlet chlorocarbene reactivities toward alkenes. Arylchlorocarbenes can be classified as electrophilic carbenes.7b,13 Accordingly, selectivity for addition to alkenes is greatest when the alkene possesses electron-donating substituents. Phenylchlorocarbene reacts readily with a,b-unsaturated esters to produce cyclopropane products in high yields (eq 6).14,15

Phenylchlorocarbene may be trapped with Tri-n-butylstannane,1d substituted alkynes,1d triethylsilane,16 or cumene (eq 7).16

Transformation of phenylchlorodiazirine to 1,3-dioxolane and 1,3-dithiolane has been demonstrated (eq 8).17

The carbonyl ylide generated from arylchlorodiazirine and acetone undergoes 1,3-dipolar cycloaddition to either benzaldehyde18 or diethyl fumarate (eq 9).19

Photolysis of phenylchlorodiazirine in the presence of pyridine yields a pyridinium ylide (l = 480 nm). Cycloaddition of the pyridinium ylide to 2-Chloroacrylonitrile yields 1-cyano-3-phenylindolizine regioselectively (eq 10).20

In the reaction of arylchlorodiazirine with Allylamine, the insertion of the carbene into an N-H bond is followed by HCl elimination to give a Schiff base in good yield (eq 11).21

Related Reagents.

Diazomethane; Di-t-butyl Dicarbonate.

1. (a) Schmitz, E. Adv. Heterocycl. Chem. 1979, 24, 63. (b) Graham, W. H. JACS 1965, 87, 4396. (c) Schmitz, E. In Chemistry of Diazirines; Liu, M. T. H., Ed.; CRC Press: Boca Raton, FL, 1987; Chapter 3. (d) Padwa, A.; Eastman, D.; JOC 1969, 34, 2728.
2. (a) Liu, M. T. H. CSR 1982, 11, 127. (b) Frey, H. M. Adv. Photochem. 1966, 4, 225. (c) Liu, M. T. H. ACR 1994, 27, 287.
3. (a) Liu, M. T. H. Chem. Eng. News 1974, Sept. 9, 3. (b) Leleu, M. J. Cahiers de Notes Documentaires 1978, 93, 569.
4. Paulsen, S. R. AG 1960, 72, 781.
5. Schmitz, E.; Ohme, R. AG 1961, 73, 115.
6. (a) Schmitz, E. Dreiringe mit Zwei Heteroatomen; Springer: New York, 1967. (b) Kirmse, W. Carbene Chemistry; Academic: New York, 1971. (c) Jones, M., Jr.; Moss, R. A. Carbene; Wiley: New York, 1973; Vol. 1. (d) Moffat, J. B. In Chemistry of Diazonium and Diazo Groups; S. Patai, Ed.; Wiley: New York, 1978; Pt. 1. (e) Heine, H. W. In Small Ring Heterocycles; Wiley: New York, 1983; Vol. 2, p 547. (f) Schmitz, E. In Comprehensive Heterocyclic Chemistry; Pergamon: Oxford, 1984; Vol. 7, p 195. (g) Chemistry of Diazirines; Liu, M. T. H., Ed.; CRC Press: Boca Raton, FL 1987. (h) Regitz, M. MOC 1989, E19b.
7. (a) Moss, R. A.; In Ref. 6(g), Chapter 4. (b) Moss, R. A. ACR 1989, 22, 15.
8. Creary, X. ACR 1992, 25, 31.
9. Moss, R. A.; Cox, D. P.; Tomioka, H. TL 1984, 25, 1023.
10. Ganzer, G. A.; Sheridan, R. S.; Liu, M. T. H. JACS 1986, 108, 1517.
11. Bertram, A. K.; Liu, M. T. H. CC 1993, 467.
12. Liu, M. T. H.; Toriyama, K. CJC 1972, 50, 3009.
13. Doyle, M. P. In Ref. 6(g), Chapter 8.
14. Doyle, M. P.; Loh, K-L.; Nishioka, L. I.; McVickar, M. B.; Liu, M. T. H. TL 1986, 27, 4395.
15. Soundararajan, N.; Platz, M. S.; Jackson, J. E.; Doyle, M. P.; Oon, S.-M.; Liu, M. T. H.; Anand, S. M. JACS 1988, 110, 7143.
16. Doyle, M. P.; Taunton, J.; Oon, S.-M.; Liu, M. T. H.; Soundararajan, N.; Platz, M. S.; Jackson, J. E. TL 1988, 29, 5863.
17. Liu, M. T. H.; Kokosi, J. H 1985, 3049.
18. Ibata, T.; Toyoda, J.; Liu, M. T. H. CL 1987, 2135.
19. Soundararajan, N.; Jackson, J. E.; Platz, M. S.; Liu, M. T. H. TL 1988, 29, 3419.
20. Bonneau, R.; Liu, M. T. H.; Lapouyade, R. JCS(P1) 1989, 1547.
21. Liu, M. T. H.; Romashin, Y. N.; Venkatachalam, T.K. CJC 1994, 72, 1961.

Michael T. H. Liu

University of Prince Edward Island, Charlottetown, PE, Canada

Copyright 1995-2000 by John Wiley & Sons, Ltd. All rights reserved.