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Synlett 2005(2): 223-226  
DOI: 10.1055/s-2004-836061
LETTER
© Georg Thieme Verlag Stuttgart · New York

A Simple Protocol for Efficient N-Chlorination of Amides and Carbamates

Lidia De Luca, Giampaolo Giacomelli*, Giammario Nieddu
Dipartimento di di Chimica, Università degli Studi di Sassari, via Vienna 2, 07100 Sassari, Italy
Fax: +39(079)212069; e-Mail: ggp@uniss.it;
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Publication History

Received 11 October 2004
Publication Date:
17 December 2004 (online)

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Abstract

N-Chlorination of various amides, lactams, and carbamates with very cheap trichloroisocyanuric acid proceeds efficiently under very mild conditions. Excellent results were also observed for the N-chlorination of carbamates of free amino acids.

Key words

amides - amino acids - N-chlorination - trichloroisocyanuric acid

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All solvents and reagents were used as obtained from commercial source. Standard 1H NMR and 13C NMR were recorded at 300 MHz and 75.4 MHz, from CDCl3 solutions. Mass spectra were recorded at 70 eV with a direct probe for sample introduction. All known compounds have analytical data corresponding to literature data. All runs were conducted at least in duplicate.
Typical Procedure for the Preparation of N -Chloro-amides.
Trichloroisocyanuric acid (5.25 mmol) was added at 0 °C to a well stirred solution of the amide (5 mmol) in CH2Cl2 (30 mL) and the mixture was kept at r.t. for the required time, monitoring (TLC) till completion. Then the mixture was filtered on Celite and the solution evaporated under reduced pressure affording the N-chloro derivative.
Spectroscopic Data of Selected Compounds:
( S ) - 2-( N -Chloroamino- N - tert -butoxycarbonyl)-3-phenylpropanoic Acid ( 9): [α]D 25 -54.98 (c 1, CH2Cl2). 1H NMR: δ = 10.51 (s, 1 H), 7.35-7.05 (m, 5 H), 4.60 (m, 1 H), 3.35-2.92 (m, 2 H), 1.40 (s, 9 H) ppm. 13C NMR: δ = 174.9, 156.0, 139.4, 128.9, 128.5, 127.1, 79.5, 54.4, 37.7, 28.2 ppm. MS (ES+): m/e (relative intensity) = 301 (32), 300(1), 299 (100). IR (film): 1255 cm-1.
( S )-Methyl 2-( N -Chloramino- N -benzyloxycarbonyl)-4-methylpentanoate ( 12): [α]D 20 -19.81 (c 0.5, CH2Cl2). 1H NMR: δ = 7.40-7.30 (m, 5 H), 5.27 (s, 2 H), 4.99 (dd, J = 3.90, 11.70 Hz, 1 H), 3.70 (s, 3 H), 2.06-1.85 (m, 1 H), 1.77-1.59 (m, 2 H), 0.94 (d, 6 H) ppm. 13C NMR: δ = 170.3, 156.2, 135.3, 128.9, 128.5, 127.8, 66.9, 53.4, 52.4, 41.6, 24.2, 23.0, 20.7 ppm. MS (ES+): m/e (relative intensity) = 315 (34), 314 (15), 313 (100). IR (film): 1243 cm-1.
(2 S ,3 S )-2- N- Chloramino- N -benzyloxycarbonyl)-3-methylpentanoic Acid ( 13): [α]D 20 -4.52 (c 0.5, CH2Cl2). 1H NMR δ = 7.37-7.29 (m, 5 H), 5.08 (s, 2 H), 4.43-4.33 (m, 1 H), 2.02-1.80 (m, 1 H), 1.62-1.39 (m, 1 H), 1.28-1.13 (m, 1 H), 0.92 (m, 6 H) ppm. 13C NMR: δ = 173.8, 156.3, 135.1, 128.8, 128.4, 128.2, 69.4, 58.2, 37.5, 24.6, 15.4, 10.3 ppm. MS (ES+): m/e (relative intensity) = 301 (32), 300(6), 299 (100). IR (film): 1267 cm-1.
( S )-Methyl 2-[ N -Chloramino- N -(9 H -fluoren-9-yl)meth-oxycarbonyl]-3-methylbutanoate ( 14): [α ]D 20 -4.13 (c 0.1, CH2Cl2). 1H NMR: δ = 7.62 (d, 2 H), 7.56 (d, 2 H), 7.26-7.13 (m, 4 H), 4.47-4.35 (m, 2 H), 4.30 (m, 1 H), 4.19 (t, 1 H), 3.76 (s, 3 H), 2.25-2.10 (m, 1 H), 0.97 (d, 3 H), 0.92 (d, 3 H) ppm. 13C NMR: δ = 172.6, 156.0, 145.4, 138.7, 128.9, 128.1, 125.4, 120.9, 67.8, 59.0, 53.4, 52.2, 31.1, 18.8, 17.5 ppm. MS (ES+): m/e (relative intensity) = 389 (35), 387 (100), 388 (19), 390 (5). IR (film): 1216 cm-1. Anal. Calcd for C21H22ClNO4 (387.86): C, 65.03; H, 5.72; Cl, 9.14; N, 3.61. Found: C, 65.05; H, 5.78; Cl, 9.18; N, 3.64.
( S )-2-[ N -Chloramino- N -(9 H -fluoren-9-yl)methoxy-carbonyl]-3-hydroxypropanoic Acid ( 15): [α]D 20 -11.96 (c 0.2, CH2Cl2). 1H NMR: δ = 10.41 (s, 1 H), 7.43 (d, 2 H), 7.27-7.12 (m, 6 H), 6.47 (br s, 1 H), 4.46 (s, 2 H), 4.18-3.70 (m, 4 H) ppm. 13C NMR: δ = 173.8, 156.6, 145.2, 144.8, 129.0, 128.2, 125.2, 120.8, 67.9, 55.9, 46.8 ppm. MS (ES+): m/e (relative intensity) = 363 (28), 361 (100), 336 (19), 364 (5). IR (film): 1230 cm-1. Anal. Calcd for C18H16ClNO5 (361.07): C, 59.76; H, 4.46; Cl, 9.80; N, 3.87. Found: C, 59.72; H, 4.48; Cl, 9.80; N, 3.84.

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Typical Procedure for the Preparation of N -Chloroamides from Primary Amides.
Trichloroisocyanuric acid (1.60 mmol) was added slowly, in small portions, and at 0 °C to a well stirred solution of the amide (5 mmol) in dry acetone:CHCl3 (1:2 solution, 30 mL) and the mixture was kept at r.t. for the required time, monitoring (TLC) till completion. Then the mixture was filtered on Celite and the solution evaporated under reduced pressure affording the N-chloro derivatives 16 and 17. [13] [16]