LETTER
Aerobic Photooxidation of Benzylamide
677
hν
I2
2 I•
1)
2)
O•
I•
HI
HI or
solvent
O
O
O
O
O2
•
Ar
N
H
Ar
N
Ar
N
H
H
20
21
I
OH
HI
HI
I2
IOH
O
H
O
O
OH
O
O
O
Ar
N
Ar
Ar
N
H
Ar
N
H
HI
22
23
24
O
N
H
O2, hν
2 HI
3)
I2 + H2O
IOH + HI
I2 + H2O
Scheme 2 Plausible path of the aerobic photooxidation of amide
N-Acetyl-4-methoxybenzamide (4)
iodine. This oxidation is a facile and convenient method
in the viewpoint of synthetic organic chemistry. Further
studies directed toward the elucidation of scope, mecha-
nism, and additional applications are progress in our lab-
oratory.
1H NMR (400 MHz, CDCl3): d = 9.19 (s, 1 H), 7.85 (d,
J = 9.0 Hz, 2 H), 6.93 (d, J = 9.0 Hz, 2 H), 3.83 (s, 3 H), 2.56
(s, 3 H). IR (KBr): 3233, 1712, 1689, 1607, 1472, 1251, 854
cm-1. HRMS (EI+): m/z calcd for C10H11NO3 [M+]:
193.07390; found: 193.07484.
N-Acetyl-4-methylbenzamide (6)
1H NMR (400 MHz, CDCl3): d = 9.17 (s, 1 H), 7.80 (d,
J = 8.3 Hz, 2 H), 7.29 (d, J = 7.8 Hz, 2 H), 2.60 (s, 3 H), 2.42
(s, 3 H). IR (KBr): 3263, 1725, 1611, 1506, 1231 cm–1.
HRMS (EI+): m/z calcd for C10H11 NO2 [M+]: 177.07898;
found: 177.07970.
References and Notes
(1) Comprehensive Organic Transformations: A Guide to
Functional Group Preparations; Larock, R. C., Ed.; Wiley-
VCH: New York, 1999.
N-Acetyl-4-chlorobenzamide (8)
(2) Sheldon, R. A. Chemtech 1994, 24, 38.
1H NMR (400 MHz, CDCl3): d = 9.44 (s, 1 H), 7.88 (d,
J = 8.8 Hz, 2 H), 7.48 (d, J = 8.8 Hz, 2 H), 2.61 (s, 3 H). IR
(KBr): 3263, 1710, 1689, 1592, 1468, 750 cm-1. HRMS
(EI+): m/z calcd for C10H11NO3 [M+]: 197.02435; found:
197.02382.
(3) Nakayama, H.; Itoh, A. Chem. Pharm. Bull. 2006, 54, 1620.
(4) (a) Flitsch, W.; Hohenhorst, M. Liebigs Ann. Chem. 1990,
397. (b) Flitsch, W.; Pandl, K.; Russkamp, P. Liebigs Ann.
Chem. 1983, 529.
(5) Irreversible inhibition of mammalian and insect peptidyl-
glycine a-hydroxylating monooxygenases (PHMs), which
are peptide amidating enzymes, by N-formyl amides was
reported, see: Klinge, M.; Cheng, H.; Zabriskie, T. M.;
Vederas, J. C. J. Chem. Soc., Chem. Commun. 1994, 1379.
(6) Baburao, K.; Costello, A. M.; Petterson, R. C.; Sander, G. E.
J. Chem. Soc. C 1968, 2779.
(7) Lalonde, R. T.; Davis, C. B. J. Org. Chem. 1970, 35, 771.
(8) Dunbar, R. E.; Swenson, W. M. J. Org. Chem. 1958, 23,
1793.
(9) Atanassova, I. A.; Petrov, J. S.; Ognjanova, V. H.; Mollov,
N. M. Synth. Commun. 1990, 20, 2083.
N-(2-Methybenzyl)acetamide (9)
1H NMR (400 MHz, CDCl3): d = 7.23-7.19 (m, 4 H), 5.56
(s, 1 H), 4.43 (d, J = 5.3 Hz, 2 H), 2.32 (s, 3 H), 2.01 (s, 3 H).
13C NMR (400 MHz, CDCl3): d = 169.7, 136.5, 135.8,
130.6, 128.7, 127.8, 126.2, 41.9, 23.1, 19.0. IR (KBr): 3293,
1637, 1547, 742 cm-1. Anal. Calcd for C10H13NO: C, 73.59;
H, 8.03; N, 8.58. Found: C, 73.53; H, 8.14; N, 8.63.
N-Acetyl-2-methylbenzamide (10)
1H NMR (400 MHz, CDCl3): d = 8.50 (s, 1 H), 7.41 (d,
J = 5.3 Hz, 1 H), 7.36 (t, J = 7.6 Hz, 1 H), 7.24-7.22 (m, 2
H), 2.52 (s, 3 H), 2.44 (s, 3 H). 13C NMR (400 MHz, CDCl3):
d = 172.9, 167.9, 137.4, 133.9, 131.7, 131.5, 126.9, 126.0,
23.4, 20.0. IR (KBr): 3248, 1727, 1506, 1221, 738 cm-1.
Anal. Calcd for C10H11NO2: C, 67.63; H, 6.26; N,7.90.
Found: C, 67.63; H, 6.27; N, 7.75.
(10) Seiller, B.; Heins, D.; Bruneau, C.; Dixneul, P. H.
Tetrahedron Lett. 1995, 51, 10901.
(11) A typical procedure follows: A dry EtOAc solution (5 mL)
of the N-benzylacetamide (1, 0.3 mmol) and I2 (0.003 mmol)
in a pyrex test tube equipped with an O2 balloon, was
irradiated without stirring condition for 48 h with a 500 W
Xenon lamp, which was set from the test tube in the distance
of 45 cm. The reaction mixture was concentrated under
reduced pressure, and the pure product was obtained by
preparative TLC.
N-(1-Naphthylmethyl)acetamide (17)
1H NMR (400 MHz, CDCl3): d = 7.99 (d, J = 7.7 Hz, 1 H),
7.86 (d, J = 7.4 Hz, 1 H), 7.79 (t, J = 4.8 Hz, 1 H), 7.55-7.48
(m, 2 H), 7.40 (d, J = 4.8 Hz, 2 H), 5.87 (s, 1 H), 4.83 (d,
J = 5.3 Hz, 2 H), 1.96 (s, 3 H). 13C NMR (400 MHz, CDCl3):
d = 169.7, 133.8, 133.5, 131.4, 128.7, 128.6, 126.7, 126.6,
Synlett 2008, No. 5, 675–678 © Thieme Stuttgart · New York