Chloramine1

NH2Cl

[10559-90-3]  · ClH2N  · Chloramine  · (MW 51.48)

(aminating agent; oxidizing agent)

Alternate Names: chloramide; monochloramine.

Physical Data: mp -66 °C.2

Solubility: sol H2O, ether, methylene chloride, alcohol; slightly sol benzene, carbon tetrachloride.

Preparative Methods: prepared in situ by the reaction of aqueous NH3 and NaOCl;3 this aqueous solution [chloramine (aq)] can frequently be used for subsequent reactions; however, in many cases it is advisable to use an anhydrous ethereal solution of chloramine [chloramine (anhyd)];4 chloramine (g) has been prepared by the gas phase reaction of Cl2 with excess NH3,5 but this appears to be synthetically less useful.

Handling, Storage, and Precautions: although chloramine (aq or anhyd) is generally prepared immediately before use, storage at 0 °C for short periods of time (<=1 h) does not appear to be detrimental; only dilute solutions4 should be prepared, as more concentrated solutions decompose readily to N2, Cl2, and NCl3; use in a fume hood.

Amination of Organometallic Reagents.

Organoboranes react with chloramine (aq) under alkaline conditions to afford fair to good yields of primary amines, thus providing a convenient route to amines from alkenes (eq 1).6 However, Hydroxylamine-O-sulfonic Acid (especially in DME) was found to be a more effective aminating agent, in terms of both yield and convenience.7 Hydroxylamine and Hydrazine were ineffective, and N-chlorodimethylamine gave either chloroalkanes8 or alkyldimethylamines,9 depending on the reaction conditions (radical vs. polar mechanism).

Chloramine (anhyd) reacts with Grignard reagents to furnish amines in poor to good yield.10 Chloromagnesium Grignard reagents gave better yields than the bromo or iodo compounds, while the dialkylmagnesium reagents gave excellent yields.11 Phenyl Grignard reagents gave poor yields of amines, the aromatic chlorides being obtained instead.10b Organolithium and organozinc reagents also react with chloramine (anhyd) to give amines.12

Reaction with Alcohol Anions.

Chloramine (anhyd) reacts with the sodium salts of aliphatic alcohols to give fair yields of the O-alkylhydroxylamines.1a,13,14 The reaction with phenoxide anions, however, takes several different paths. While ortho-unsubstituted phenoxide ions give o-aminophenols (in poor yield) by simple C-amination, treatment of 2,6-disubstituted phenolic salts in molten phenols with <1 equiv of chloramine (anhyd) proceeds further with subsequent ring expansion to give 1,3-dihydro-2H-azepinones (eq 2).15 Unsymmetrical 2,6-disubstituted phenols gave mixtures of the two possible ring expanded products, the ratios being governed primarily by steric control.15d Use of excess chloramine (anhyd) gave products due to oxidative coupling of the phenol.16 Placement of a carbonyl group in the ortho position gave rise to 2-hydroxyanilides (eq 3).17

Reaction with Nitrogen-Containing Compounds.

Chloramine (aq) and substituted chloramines react with aliphatic amines to give hydrazines.1a,1b,18 Hydroxylamine-O-sulfonic Acid, however, is often superior to chloramine (aq).19

a-Oximino ketones react with chloramine (aq) to give a-diazo ketones (Forster reaction).20 When combined with a photolytic Wolff rearrangement, this provides a convenient, generally useful method of ring contraction.21 This sequence of reactions has demonstrated great promise in the synthesis of nor-steroids (eq 4).22

The reaction of chloramine (anhyd) with toluenesulfonamides provides a method for either hydrodeamination or halodeamination of primary amines (eq 5).23 This method has demonstrated superiority to the related hydrodeamination using hydroxylamine-O-sulfonic acid in aqueous base.24

Oxidations.

Chloramine (anhyd) has been reported to oxidize anilines to mixtures of cis- and trans-azobenzenes.4b Although the yields were modest (20-50%), this method does provide access to the relatively rare cis isomers. Other oxidants (Manganese Dioxide, Lead(IV) Acetate or (Diacetoxyiodo)benzene) give only the trans isomers.

Benzyl alcohols were also oxidized to carbonyl compounds in good to excellent yield, but this method has not been extended to aliphatic (nonbenzylic) alcohols.

Related Reagents.

Ammonia; Chloramine-Aluminum(III) Chloride; Chloramine-T; Hydrazine; Hydroxylamine-O-sulfonic Acid; Trichloramine.


1. (a) Theilacker, W.; Wegner, E. AG 1960, 72, 127. (b) Theilacker, W.; Wegner, E. In Newer Methods of Preparative Organic Chemistry; Academic: New York, 1964; Vol. 3, pp 303-317. (c) Kovacic, P.; Lowery, M. K.; Field, K. W. CRV 1970, 70, 639. (d) See also: Minisci, F. S 1973, 1, for a discussion of chloramines.
2. CRC Handbook of Chemistry and Physics, 74th ed.; Lide, D. R., Ed.; CRC: Boca Raton, FL, 1993; pp 4-52.
3. (a) Raschig, F. CB 1907, 40, 4580. (b) Hauser, C. R.; Gillaspie, A. G.; Le Maistre, J. W. JACS 1935, 57, 567.
4. (a) Coleman, G. H.; Johnson, H. L. Inorg. Synth. 1939, 1, 59. (b) Jaffari, G. A.; Nunn, A. J. JCS(C) 1971, 823.
5. Sisler, H. H.; Neth, F. T.; Drago, R. S.; Yaney, D. JACS 1954, 76, 3906.
6. (a) Brown, H. C.; Heydkamp, W. R.; Breuer, E.; Murphy, W. S. JACS 1964, 86, 3565. (b) Kabalka, G. W.; Wang, Z. SC 1990, 20, 2113.
7. Rathke, M. W.; Inoue, N.; Varma, K. R.; Brown, H. C. JACS 1966, 88, 2870.
8. Sharefkin, J. G.; Banks, H. D. JOC 1965, 30, 4313.
9. Davies, A. G.; Hook, S. C. W.; Roberts, B. P. JOM 1970, 23, C11.
10. (a) Coleman, G. H.; Hauser, C. R. JACS 1928, 50, 1193. (b) Le Fèvre, R. J. W. JCS 1932, 1745.
11. Coleman, G. H.; Blomquist, R. F. JACS 1941, 63, 1692.
12. Coleman, G. H.; Hermanson, J. L.; Johnson, H. L. JACS 1937, 59, 1896.
13. Theilacker, W.; Ebke, K. AG 1956, 68, 303.
14. Theilacker, W. AG 1960, 72, 498.
15. (a) Paquette, L. A. JACS 1962, 84, 4987. (b) Paquette, L. A. JACS 1963, 85, 3288. (c) Paquette, L. A. OSC 1973, 5, 408. (d) Paquette, L. A.; Farley, W. C. JACS 1967, 89, 3595.
16. Paquette, L. A.; Farley, W. C. JOC 1967, 32, 2718.
17. Crochet, R. A.; Kovacic, P. CC 1973, 716.
18. (a) Audrieth, L. F.; Diamond, L. H. JACS 1954, 76, 4869. (b) Rowe, R. A.; Audrieth, L. F. JACS 1956, 78, 563.
19. (a) Gever, G.; Hayes, K. JOC 1949, 14, 813. (b) Gösl, R.; Meuwsen, A. CB 1959, 92, 2521.
20. Forster, M. O. JCS 1915, 107, 260.
21. (a) Cava, M. P.; Litle, R. L.; Napier, D. R. JACS 1958, 80, 2257. (b) Weygand, F.; Bestmann, H. J. AG 1960, 72, 535.
22. (a) Cava, M. P.; Moroz, E. JACS 1962, 84, 115. (b) Meinwald, J.; Curtis, G. G.; Gassman, P. G. JACS 1962, 84, 116. (c) Muller, G.; Huynh, C.; Mathieu, J. BSF(2) 1962, 296. (d) Hassner, A.; Coulter, A. W.; Seese, W. S. TL 1962, 759. (e) Mateos, J. L.; Chao, O.; Flores, R. H. T 1963, 19, 1051. (f) Cava, M. P.; Vogt, B. R. JOC 1965, 30, 3775. (g) Wheeler, T. N.; Meinwald, J. OSC 1988, 6, 840.
23. Guziec, F. S., Jr.; Wei, D. JOC 1992, 57, 3772.
24. Nickon, A.; Hill, A. S. JACS 1964, 86, 1152.

R. Richard Goehring

Scios Nova, Baltimore, MD, USA



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