LETTER
Safe and Efficient Ritter Reactions in Flow
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(4) (a) Chang, S.-J. Org. Process Res. Dev. 1999, 3, 232.
(b) Baum, J. C.; Milne, J. E.; Murray, J. A.; Thiel, O. R.
J. Org. Chem. 2009, 74, 2207.
(5) (a) Sanz, R.; Martínez, A.; Guilarte, V.; Álvarez-Gutierrez,
J. M.; Rodrígez, F. Eur. J. Org. Chem. 2007, 4642.
(b) Veverková, E.; Toma, S. Chem. Pap. 2005, 59, 8.
(6) Rubenbauer, P.; Bach, T. Chem. Commun. 2009, 2130.
(7) Baumann, M.; Baxendale, I. R.; Martin, L. J.; Ley, S. V.
Tetrahedron 2009, 65, 6611.
(8) Ritter, J. J.; Minieri, P. P. J. Am. Chem. Soc. 1948, 70, 4045.
(9) Poechlauer, P.; Kotthaus, M.; Vorbach, M.; Deak, M.; Zich,
T.; Marr, R. PCT Int. Appl. WO 2006125502, 2006.
(10) Szmant, H. H. Organic Building Blocks of the Chemical
Industry; John Wiley & Sons: New York, 1989.
(3), 217 (49), 207 (7), 200(100), 183 (18). HRMS: m/z [M +
H]+ calcd for C14H29N2O3: 273.2173; found: 273.2177. IR
(neat): 3549, 3460, 3330, 3067, 2979, 2927, 2897, 1664,
1639, 1547, 1455, 1361, 1227, 1109 cm–1.
N-(tert-Butyl)-2-(2-iodophenyl)acetamide (14): 1H NMR
(500 MHz, CDCl3): d = 1.31 (s, 9 H, Me), 3.61 (s, 2 H, CH2),
5.22 (s, 1 H, NH), 6.98 (m, 1 H, ArH), 7.34 (m, 2 H, ArH),
7.86 (d, 1 H, J = 7.7 Hz, ArH). 13C NMR (125 MHz, CDCl3):
d = 28.7, 49.6, 51.4, 101.0, 128.8, 128.9, 130.8, 138.8, 139.8,
168.6. EI–MS: m/z (%) = 318 [M+](4), 302 (13), 281 (4), 262
(28), 244 (100), 232 (6). HRMS: m/z [M + H]+ calcd for
C12H17INO: 318.0349; found: 318.0349. IR (neat): 3378,
3276, 2972, 2960, 1643, 1552, 1466, 1448, 1417, 1360,
1341, 1288, 1259, 1155, 1014 cm–1.
(11) The micromixing device ‘Comet X-01’, available from
Techno Applications Co., Ltd, 34-16-204, Hon,
(13) Jirgensons, A.; Kauss, V.; Kalvinsh, I.; Gold, M. R.
Synthesis 2000, 1709.
Denenchofu, Oota, Tokyo 145-0072, Japan, was used.
(12) Syringe A was loaded with 85% H2SO4 (5 mL). Syringe B
was loaded with alcohol (6 mmol) and nitrile (6 mmol),
diluted with acetic acid to 5 mL. The PTFE micromixer and
the attached PTFE tubing (2 m, 0.5 mm inner diameter) were
inserted into the heating bath and the temperature was
adjusted to 45 °C (85 °C for secondary alcohols). The flow
rate was set at 0.1 mL/min (reaction time: 3 min). The crude
product was quenched by dropping into excess of ice–2 M
NaOH. After the reaction, the tube was flushed with EtOAc
and the crude mixture was washed with aq 2 M NaOH (80
mL) and EtOAc (3 × 100 mL). The organic layers were
combined, dried over MgSO4 and the solvent was removed
under reduced pressure.
(14) Ge, Y.; Hu, L. Tetrahedron Lett. 2007, 48, 4585.
(15) Kato, T.; Reed, C. A. Angew. Chem. Int. Ed. 2004, 43, 2908.
(16) (a) Hudson, C. E.; McAdoo, D. J. Int. J. Mass Spectrom.
2002, 214, 315. (b) Traeger, J. C.; McAdoo, D. J.; Hudson,
C. E.; Giam, C. S. J. Am. Soc. Mass Spectrom. 1998, 9, 21.
(c) Bowen, R. D.; Harrison, A. G. Org. Mass Spectrom.
1981, 16, 180. (d) Wendelboe, J. F.; Bowen, R. D.;
Williams, D. H. J. Am. Chem. Soc. 1981, 103, 2333.
(17) (a) Xu, T.; Haw, J. F. J. Am. Chem. Soc. 1994, 116, 7753.
(b) Lercher, J. A.; van Santen, R. A.; Vinek, H. Catal. Lett.
1994, 27, 91. (c) Yang, S.; Kondo, J. N.; Domen, K. Chem.
Commun. 2001, 2008.
(18) (a) Boronat, M.; Corma, A. Appl. Catal. A 2008, 336, 2.
(b) Kotrel, S.; Knözinger, H.; Gates, B. C. Microporous
Mesoporous Mater. 2000, 35-36, 11. (c) Hunter, K. C.;
East, A. L. L. J. Phys. Chem. A 2002, 106, 1346.
(d) Williams, B. A.; Ji, W.; Miller, J. T.; Snurr, R. Q.; Kung,
H. H. Appl. Catal. A 2000, 203, 179.
Selected Spectroscopic Data:
3,3¢-Oxybis[N-(tert-butyl)propanamide] (13): 1H NMR (500
MHz, CDCl3): d = 1.31 (s, 18 H, Me), 2.34 (t, 4 H, J = 6.0
Hz, CH2), 3.66 (t, 4 H, J = 6.0 Hz, CH2), 5.85 (s, 2 H, NH).
13C NMR (125 MHz, CDCl3): d = 28.8, 37.8, 51.0, 67.1,
170.2. EI–MS: m/z (%) = 272 [M+](3), 257 (48), 242 (6), 229
(19) Olah, G. A.; Prakash, G. K. S.; Rasul, G. Dalton Trans.
2008, 521.
Synlett 2010, No. 20, 3099–3103 © Thieme Stuttgart · New York