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Synlett 2009(5): 798-802  
DOI: 10.1055/s-0028-1087943
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Facile Procedure for the Synthesis of N-Aryl-N-hydroxy Carbamates

Achim Porzellea, Michael D. Woodrowb, Nicholas C. O. Tomkinson*a
a School of Chemistry, Main Building, Cardiff University, Park Place, Cardiff, CF10 3AT, UK
e-Mail: porzellea@cardiff.ac.uk; e-Mail: tomkinsonnc@cardiff.ac.uk;
b ImmunoInflammation Centre of Excellence for Drug Discovery, GlaxoSmithKline Medicines Research Centre, Stevenage, Hertfordshire, SG1 2NY, UK
Further Information

Publication History

Received 8 December 2008
Publication Date:
24 February 2009 (online)

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Abstract

An efficient one-pot procedure for the zinc-mediated reduction of nitroarenes in the presence of chloroformates leading to the corresponding N,O-bisprotected hydroxylamine is described. Reactions proceed smoothly under ambient conditions in THF-­water mixtures in good to excellent yield (34-81%). Solvolysis of the bisprotected hydroxylamines with sodium methoxide at room temperature provides access to synthetically versatile N-aryl-N-­hydroxy carbamates in excellent yields (89-97%).

Key words

hydroxylamine - carbamate - zinc-mediated reduction

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21

Spectroscopic Data for New CompoundsBenzyl N-Phenyl-N-(benzoxycarbonyloxy) Carbamate
¹H NMR (400 MHz, CDCl3): δ = 7.47-7.45 (m, 2 H), 7.40-7.26 (m, 13 H), 5.26 (s, 2 H), 5.22 (s, 2 H). ¹³C NMR (62.5 MHz, CDCl3): δ = 154.2, 153.4, 139.4, 135.4, 134.1, 129.1, 129.0, 128.8, 128.7, 128.6, 128.5, 128.4, 128.0, 127.7, 124.0, 71.6, 68.6. HRMS: m/z calcd for [M + H]+ C22H19NO5Na: 400.1161; found: 400.1167.
Benzyl N-4-Tolyl-N-(benzoxycarbonyloxy) Carbamate
¹H NMR (400 MHz, CDCl3): δ = 7.40-7.29 (m, 12 H), 7.18 (d, 2 H, J = 8.0 Hz), 5.27 (s, 2 H), 5.24 (s, 2 H), 2.25 (s, 3 H). ¹³C NMR (62.5 MHz, CDCl3): δ = 154.7, 153.0, 140.7, 136.0, 135.5, 134.5, 129.7, 129.0, 128.8, 128.7, 128.6, 128.4, 122.0, 70.9, 67.2, 20.9. HRMS: m/z calcd for [M + H]+ C23H22NO5: 392.1498; found: 392.1497.
Benzyl N-4-Cyano-N-(benzoxycarbonyloxy) Carbamate
¹H NMR (400 MHz, CDCl3): δ = 7.65-7.58 (m, 4 H), 7.39-7.31 (m, 10 H), 5.28 (s, 2 H), 5.27 (s, 2 H). ¹³C NMR (62.5 MHz, CDCl3): δ = 153.6, 151.9, 143.0, 134.7, 133.7, 133.0, 129.3, 128.8, 128.7, 128.6, 128.2, 120.1, 118.4, 109.1, 72.3, 69.2. HRMS: m/z calcd for [M + NH4]+ C23H22N3O5: 420.1559; found: 420.1570.
Benzyl N-3-Trifluoromethylphenyl-N-(benzoxycarbonyl-oxy) Carbamate
¹H NMR (400 MHz, CDCl3): δ = 7.74 (br s, 1 H), 7.66-7.64 (m, 1 H), 7.50-7.49 (m, 2 H), 7.39-7.30 (m, 10 H), 5.27 (s, 2 H), 5.26 (s, 2 H). ¹³C NMR (62.5 MHz, CDCl3): δ = 153.9, 152.7, 140.0, 135.0, 133.9, 131.8 (q, CF3, J = 42 Hz), 129.6, 129.1, 128.8, 128.7, 128.6, 128.5, 128.1, 125.6, 123.6, 123.6, 119.5, 72.0, 69.0. HRMS: m/z calcd for [M + NH4]+ C23H22F3N2O5: 463.1481; found: 463.1472.
Methyl N-2-Tolyl-N-(methoxycarbonyloxy) Carbamate
¹H NMR (400 MHz, CDCl3): δ = 7.44 (d, 1 H, J = 7.8 Hz), 7.29-7.24 (m, 3 H), 3.88 (s, 3 H), 3.82 (s, 3 H), 2.37 (s, 3 H). ¹³C NMR (62.5 MHz, CDCl3): δ = 154.8, 154.8, 137.8, 137.4, 131.1, 129.5, 128.5, 126.7, 56.2, 54.0, 17.16. HRMS: m/z calcd for [M + H]+ C11H14NO5: 240.0872; found: 240.0867.
Methyl N-3-Tolyl-N-(methoxycarbonyloxy) Carbamate
¹H NMR (500 MHz, CDCl3): δ = 7.31-7.28 (m, 3 H), 7.15 (d, 1 H, J = 7.0 Hz), 3.94 (s, 3 H), 3.87 (s, 3 H), 2.39 (s, 3 H). ¹³C NMR (125 MHz, CDCl3): δ = 154.7, 154.1, 139.2, 139.1, 128.9, 128.8, 125.1, 121.5, 56.4, 54.0, 21.5. HRMS: m/z calcd for [M + H]+ C11H14NO5: 240.0872; found: 240.0863.
Methyl N-4-Tolyl-N-(methoxycarbonyloxy) Carbamate
¹H NMR (400 MHz, CDCl3): δ = 7.34 (d, 2 H, J = 8.1 Hz), 7.19 (d, 2 H, J = 8.1 Hz), 3.90 (s, 3 H), 3.83 (s, 3 H), 2.36 (s, 3 H). ¹³C NMR (62.5 MHz, CDCl3): δ = 154.8, 154.3, 138.4, 136.8, 129.7, 125.1, 56.3, 53.9, 21.1. HRMS: m/z calcd for [M + H]+ C11H11NO5: 240.0866; found: 240.0868.
Methyl N-3-Trifluoromethylphenyl-N-(methoxycar-bonyloxy) Carbamate
¹H NMR (400 MHz, CDCl3): δ = 7.75 (s, 1 H), 7.68-7.66 (m, 1 H), 7.54-7.52 (m, 2 H), 3.96 (s, 3 H), 3.89 (s, 3 H). ¹³C NMR (62.5 MHz, CDCl3): δ = 154.4, 153.4, 139.9, 131.4 (q, CF3, J = 32 Hz), 129.5, 125.9, 123.8, 121.4, 119.6, 56.7, 54.2. HRMS: m/z calcd for [M + H]+ C11H11NO5F3: 294.0589; found: 294.0589.
Methyl N-4-Iodophenyl-N-(methoxycarbonyloxy) Carbamate
¹H NMR (400 MHz, CDCl3): δ = 7.63 (d, 2 H, J = 4.8 Hz), 7.14 (d, 2 H, J = 4.8 Hz), 3.84 (s, 3 H), 3.77 (s, 3 H). ¹³C NMR (62.5 MHz, CDCl3): δ = 154.5, 153.5, 139.1, 138.1, 125.2, 92.3, 56.6, 54.2. HRMS: m/z calcd for [M + H]+ C10H11NO5 ¹²7I: 351.9682; found: 351.9675.
Methyl N-4-Cyanophenyl-N-(methoxycarbonyloxy) Carbamate
¹H NMR (400 MHz, CDCl3): δ = 7.63 (d, 2 H, J = 8.1 Hz), 7.58 (d, 2 H, J = 7.0 Hz), 3.94 (s, 3 H), 3.88 (s, 3 H). ¹³C NMR (62.5 MHz, CDCl3): δ = 154.1, 152.5, 143.0, 133.0, 120.3, 118.3, 109.2, 57.0, 54.4. HRMS: m/z calcd for [M + NH4]+ C11H14N3O5: 268.0928; found: 268.0931.

22

Phenyl N-Phenyl-N-hydroxy Carbamate
¹H NMR (400 MHz, CDCl3): δ = 7.85 (br s, 1 H), 7.54 (d, 2 H, J = 7.8 Hz), 7.40-7.35 (m, 4 H), 7.26-7.22 (m, 2 H), 7.14 (d, 2 H, J = 7.8 Hz). ¹³C NMR (62.5 MHz, CDCl3): δ = 153.7, 150.7, 140.2, 129.5, 128.8, 126.5, 126.0, 122.5, 121.5. HRMS: m/z calcd for [M + H]+ C13H12NO3: 230.0812; found: 230.0812.
Phenyl N-4-Tolyl-N-hydroxy Carbamate
¹H NMR (400 MHz, CDCl3): δ = 7.88 (br s, 1 H), 7.41-7.33 (m, 4 H), 7.25-7.21 (m, 1 H), 7.19-7.11 (m, 4 H), 2.36 (s, 3 H). ¹³C NMR (62.5 MHz, CDCl3): δ = 153.8, 150.8, 137.7, 136.7, 129.5, 129.4, 125.9, 123.0, 121.5, 21.0. HRMS: m/z calcd for [M + NH4]+ C14H17N2O3: 261.1239; found: 261.1230.
Benzyl N-4-Tolyl-N-hydroxy Carbamate
¹H NMR (400 MHz, CDCl3): δ = 7.37-7.30 (m, 7 H), 7.15 (d, 2 H, J = 8.2 Hz), 5.21 (s, 2 H), 2.23 (s, 3 H). ¹³C NMR (62.5 MHz, CDCl3): δ = 155.6, 140.8, 138.4, 135.8, 129.2, 128.6, 128.1, 127.1, 122.7, 68.3, 21.0. HRMS: m/z calcd for [M + H]+ C15H16NO3: 258.1125; found: 258.1126. Benzyl N-4-Cyano-N-hydroxy Carbamate
¹H NMR (400 MHz, CDCl3): δ = 7.70 (d, 2 H, J = 9.0 Hz), 7.58 (d, 2 H, J = 9.0 Hz), 7.43-7.33 (m, 5 H), 5.30 (s, 2 H). ¹³C NMR (62.5 MHz, CDCl3): δ = 154.2, 144.7, 134.9, 132.7, 128.98, 128.4, 119.4, 118.8, 107.0 69.1. HRMS: m/z calcd for [M + NH4]+ C15H16N3O3: 286.1192; found: 286.1194. Benzyl N-3-Trifluoromethylphenyl-N-hydroxy Carbamate
¹H NMR (400 MHz, CDCl3): δ = 7.68 (br s, 1 H), 7.56-7.55 (m, 1 H), 7.31-7.29 (m, 2 H), 7.21-7.13 (m, 5 H), 5.10 (s, 2 H). ¹³C NMR (62.5 MHz, CDCl3): δ = 155.0, 141.4, 135.0, 131.0 (q, J = 32 Hz, CF3), 129.1, 128.7, 128.7, 128.2, 127.8, 127.1, 124.2, 118.1, 69.0. HRMS: m/z calcd for [M + NH4]+ C15H16FN2O3: 329.1108; found: 329.1110. Methyl N-2-Tolyl-N-hydroxy Carbamate
¹H NMR (400 MHz, CDCl3): δ = 9.0 (br s, 1 H), 7.36-7.33 (m, 1 H), 7.28-7.22 (m, 3 H), 3.75 (s, 3 H), 2.34 (s, 3 H). ¹³C NMR (62.5 MHz, CDCl3): δ = 157.5, 139.5, 136.2, 130.9, 128.9, 127.5, 126.6, 53.8, 17.6. HRMS: m/z calcd for [M + Na]+ C9H11NO3Na: 204.0631; found: 204.0634.
Methyl N-3-Tolyl-N-hydroxy Carbamate
¹H NMR (400 MHz, CDCl3): δ = 8.2 (br s, 1 H), 7.33-7.28 (m, 3 H), 7.06 (d, 2 H, J = 6.6 Hz), 3.84 (s, 3 H), 2.40 (s, 3 H). ¹³C NMR (62.5 MHz, CDCl3): δ = 156.4, 140.9, 138.5, 128.4, 126.9, 123.1, 119.7, 53.7, 21.5. HRMS: m/z calcd for [M]+ C9H11NO3: 181.0739; found: 181.0735.
Methyl N-4-Tolyl-N-hydroxy Carbamate
¹H NMR (400 MHz, CDCl3): δ = 2.34 (s, 3 H), 3.77 (s, 3 H), 7.15 (d, 2 H, J = 8.2 Hz), 7.33 (d, 2 H, J = 8.2 Hz), 8.55 (br s, 1 H). ¹³C NMR (62.5 MHz, CDCl3): δ = 156.4, 138.4, 136.2, 129.2, 122.8, 53.7, 21.0. HRMS: m/z calcd for [M + Na]+ C9H11NO3Na: 204.0631; found: 204.0629.
Methyl N-3-Trifluoromethylphenyl-N-hydroxy Carbamate
¹H NMR (400 MHz, CDCl3): δ = 7.80 (s, 1 H), 7.71 (d, 1 H, J = 8.0 Hz), 7.49-7.41 (m, 2 H), 7.20 (br s, 1 H), 3.89 (s, 3 H). ¹³C NMR (62.5 MHz, CDCl3): δ = 155.7, 141.3, 131.1 (q, CF3, J = 32 Hz), 129.1, 129.1, 124.1, 122.0, 117.9, 54.0. HRMS: m/z calcd for [M]+ C9H8F3NO3: 235.0456; found: 235.0453.
Methyl N-4-Iodophenyl-N-hydroxy Carbamate
¹H NMR (400 MHz, MeOD): δ = 7.65 (d, 2 H, J = 7.0 Hz), 7.25 (d, 2 H, J = 7.0 Hz), 3.83 (s, 3 H). ¹³C NMR (62.5 MHz, MeOD): δ = 156.9, 143.5, 138.6, 123.6, 89.0, 53.8. HRMS: m/z calcd for [M + H]+ C8H8INO3: 292.9549; found: 292.9550.
Methyl N-4-Cyanophenyl-N-hydroxy Carbamate
¹H NMR (400 MHz, CDCl3): δ = 7.69 (d, 2 H, J = 7.0 Hz), 7.60 (d, 2 H, J = 7.0 Hz), 3.90 (s, 3 H). ¹³C NMR (62.5 MHz, CDCl3): δ = 154.6, 144.3, 132.8, 119.3, 118.7, 107.3, 54.3. HRMS: m/z calcd for [M + Na]+ C9H8N2O3Na: 215.0427; found: 215.0427.