Synlett 2004(13): 2335-2338  
DOI: 10.1055/s-2004-832837
LETTER
© Georg Thieme Verlag Stuttgart · New York

Direct Microwave Synthesis of N,N′-Diacylhydrazines and Boc-Protected Hydrazides by in situ Carbonylations under Air

Maria Antonia Herrero, Johan Wannberg, Mats Larhed*
Organic Pharmaceutical Chemistry, Department of Medicinal Chemistry, Uppsala University, Box-574, 75123 Uppsala, Sweden
Fax: +46(18)4714474; e-Mail: mats@orgfarm.uu.se;
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Publikationsverlauf

Received 11 July 2004
Publikationsdatum:
24. September 2004 (online)

Abstract

Palladium-catalyzed hydrazidocarbonylations of aryl iodides and bromides were performed by controlled microwave irradiation, employing Mo(CO)6 as a convenient CO source. A fluorous phosphine ligand was succesfully used to recycle the catalytic system. Finally, dehydration of a diacylhydrazine to the corresponding 1,3,4-oxadiazole was achieved with POCl3 in a one-pot procedure.

1

New address: Department of Organic Chemistry, C. C., Castilla-La Mancha University, 13071 Ciudad Real, Spain. Email: maherrer@uclm.es.

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N -(4-Methoxy)benzoyl- N ′-phenylacetylhydrazine ( 3b). Colorless solid; mp 153-154 ºC. LC-MS t R = 4.26 min, m/z = 285 [M + H+]. 1H NMR (400 MHz, CD3OD): δ = 3.58 (s, 2 H), 3.80 (s, 3 H), 6.94 (AA′XX ′, 2 H), 7.15-7.34 (m, 5 H), 7.79 (AA′XX ′, 2 H) ppm. 13C NMR (100.5 MHz, CD3OD): δ = 43.0, 57.6, 116.5 (2), 127.2, 129.6, 131.2 (2), 131.9 (2), 132.2 (2), 137.9, 166.0, 170.6, 174.9 ppm. Anal. Calcd for C16H16N2O3 (%): C, 67.59; H, 5.67; N, 9.85. Found: C, 67.40; H, 5.78; N, 9.70.
N -(4-Methoxy)benzoyl- N ′- tert -butoxycarbonylhydrazine ( 3c). Colorless solid; mp 148-149 °C. LC-MS t R = 4.58 min, m/z = 267 [M + H+]. 1H NMR (400 MHz, CD3CN): δ = 1.44 (s, 9 H), 3.83 (s, 3 H), 6.95 (AA′XX ′, 2 H), 7.76 (AA′XX ′, 2 H) ppm. 13C NMR (100.5 MHz, CD3CN): δ = 28.3 (3), 56.1, 81.2, 114.7 (2), 125.8, 130.1 (2), 156.5, 163.5, 167.4 ppm. Anal. Calcd for C13H18N2O4 (%): C, 58.64; H, 6.81; N, 10.52. Found: C, 58.54; H, 6.72; N, 10.66.
N -(4-Methyl)benzoyl- N ′-phenylacetylhydrazine ( 3e). Colorless solid; mp 175-176 °C. LC-MS t R = 4.71 min, m/z = 269 [M + H+]. 1H NMR (400 MHz, CD3OD): δ = 2.39 (s, 2 H), 3.63 (s, 2 H), 7.20-7.39 (m, 5 H), 7.76 (AA′XX ′, 2 H) ppm. 13C NMR (100.5 MHz, CD3OD): δ = 21.5, 41.7, 127.9, 128.7 (2), 129.5 (2), 129.8 (2), 130.1, 130.2 (2), 130.6, 136.2, 144.1, 169.2, 173.1 ppm. Anal. Calcd for C16H16N2O2 + 0.4H2O (%): C, 69.75; H, 6.15; N, 10.17. Found: C, 69.71; H, 6.04; N, 10.11.
N -(4-Methyl)benzoyl- N ′- tert -butoxycarbonylhydrazine ( 3f). Colorless solid; mp 153-154 °C. LC-MS t R = 5.05 min, m/z = 251 [M + H+]. 1H NMR (400 MHz, CDCl3): δ = 1.48 (s, 9 H), 2.38 (s, 3 H), 7.20 (AA′XX ′, 2 H), 7.70 AA′XX ′, 2 H) ppm. 13C NMR (100.5 MHz, CDCl3): δ = 21.7, 28.3 (3), 82.1, 127.4 (2), 129.1, 129.4 (2), 142.9, 155.9, 167.0 ppm. Anal. Calcd for C13H18N2O3 (%): C, 62.38; H, 7.25; N, 11.19. Found: C, 62.22; H, 7.11; N, 11.06.
N -(2-Methyl)benzoyl- N ′-phenylacetylhydrazine ( 3h). Colorless solid; mp 174-175 °C. LC-MS t R = 4.40 min, m/z = 269 [M + H+]. 1H NMR (400 MHz, CD3OD): δ = 2.40 (s, 3 H), 3.60 (s, 2 H), 7.17-7.36 (m, 8 H), 7.43 (dd, J = 7.7, 1.2 Hz, 1 H, ArH) ppm. 13C NMR (100.5 MHz, CD3OD): δ = 18.3, 40.3, 125.4, 126.7, 127.2, 128.2, 128.9, 130.2, 130.5, 134.0, 134.9, 136.4, 165.5, 171.6 ppm. Anal. Calcd for C16H16N2O2 + 0.5H2O (%): C, 69.30; H, 6.18; N, 10.10. Found: C, 69.45; H, 6.19; N, 9.96.
N -Phenylacetyl- N ′-(4-trifluoromethyl)benzoylhydrazine ( 3k). Colorless solid; mp 195-196 °C. LC-MS t R = 5.92 min, m/z = 323 [M + H+]. 1H NMR (400 MHz, CD3OD): δ = 3.61 (s, 2 H), 7.15-7.35 (m, 5 H), 7.76 (AA′XX ′, 2 H), 7.99 (AA′XX ′, 2 H) ppm. Anal. Calcd for C16H13F3N2O2 (%): C, 59.63; H, 4.07; N, 8.69. Found: C, 59.41; H, 3.96; N, 8.59.
N - tert -Butoxycarbonyl- N ′-(4-trifluoromethyl)-benzoylhydrazine ( 3l). Colorless solid; mp 143-144 °C. LC-MS t R = 6.29 min, m/z = 305 [M + H+]. 1H NMR (400 MHz, CD3OD): δ = 1.45 (s, 9 H), 7.80 (AA′XX ′, 2 H), 7.94 (AA′XX ′, 2 H) ppm. Anal. Calcd for C13H15F3N2O3 (%): C, 51.32; H, 4.97; N, 9.21. Found: C, 51.07; H, 5.06; N, 9.35.

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2-Phenyl-5-(4-trifluoromethyl)phenyl-1,3,4-oxadiazole ( 6). Colorless solid; mp 151-152 °C. LC-MS (4 mL/min, 0-70% MeCN in H2O, 8 min gradient, ESI+) t R = 6.91 min, m/z = 291 [M + H+]. 1H NMR (400 MHz, CDCl3): δ = 7.50-7.60 (m, 3 H), 7.80 (AA′XX ′, 2 H), 8.16 (dd, J = 7.9 and 1.7 Hz, 2 H), 8.27 (AA′XX ′, 2 H). Anal. Calcd for C15H9F3N2O (%): C, 62.07; H, 3.13; N, 9.65. Found: C, 62.08; H, 3.18; N, 9.73.