InBr3- and AgOTf-catalyzed beckmann rearrangement of (E)-benzoheterocyclic oximes

Article abstract of DOI:10.1002/jhet.438

Beckmann rearrangement of (E)-4-chromanone oxime, (E)-5-oximino-3,4- dihydro-1(2H)-benzoxepines, and (E)-5-oximino-3,4-dihydro-1(2H)-benzothiepine are catalyzed by InBr₃ and AgOTf in refluxing acetonitrile resulting in the formation of pharmaceutically active heterocycles benzoxazepin-4-one, 5-oxo-benzoxazocines, and 5-oxo-benzothiazocine derivative, respectively, in excellent yield. Copyright

Full text of DOI:10.1002/jhet.438

4
24
InBr - and AgOTf-Catalyzed Beckmann Rearrangement of
3
Vol 49
(
E)-Benzoheterocyclic Oximes
Vishnu K. Tandon,* Anoop K. Awasthi, Hardesh K. Maurya,
and Pushyamitra Mishra
Department of Chemistry, University of Lucknow, Lucknow 226 007, India
*
E-mail: vishnutandon@yahoo.co.in
Received October 29, 2009
DOI 10.1002/jhet.438
Published online 7 December 2011 in Wiley Online Library (wileyonlinelibrary.com).
Beckmann rearrangement of (E)-4-chromanone oxime, (E)-5-oximino-3,4-dihydro-1(2H)-benzoxe-
pines, and (E)-5-oximino-3,4-dihydro-1(2H)-benzothiepine are catalyzed by InBr and AgOTf in reflux-
3
ing acetonitrile resulting in the formation of pharmaceutically active heterocycles benzoxazepin-4-one,
5
-oxo-benzoxazocines, and 5-oxo-benzothiazocine derivative, respectively, in excellent yield.
J. Heterocyclic Chem., 49, 424 (2012).
INTRODUCTION
RESULTS AND DISCUSSION
Beckmann rearrangement involving the transformation
of ketoximes into amides is a fundamental reaction in
organic synthesis and has led to numerous applications
due to the ease with which nitrogen can be inserted into
carbon chains starting from prepared ketones [1]. Gener-
ally, strong Bronstead/Lewis acids ranging from stoichi-
ometric to catalytic amounts are used to accomplish
the Beckmann rearrangement. Development of this im-
portant rearrangement promoted by a catalytic amount of
active species has been strongly desired during the last
As part of our research program to study indium bro-
mide and silver triflate for synthesis of different indus-
trially and biologically important heterocycles [11] and
indium chloride [12] catalyzed Beckmann rearrangement
of a-tetralone oxime, we became interested in the syn-
thesis of analogs of oxazine and oxazepine [11].
We have studied indium bromide, a economical
catalyst better than indium chloride and silver triflate
combination of reagents, for the synthesis of 2,3-dihy-
drobenzo[b][1,4]oxazepin-4(5H)-one (3a), 3,4-dihydro-
2H-benzo[b][1,4]oxazocin-5(6H)-ones (3b–e), and 3,4-
dihydro-2H-benzo[b][1,4]thiazocin-5(6H)-one (3f) from
corresponding oximes (2a–f), [13], which is more stable
stereoisomer than Z-oximes [14]. The (E)-oximes 2 used
for the Beckmann rearrangement were synthesized from
decade. In recent years, new reagents such as BF . Et O
3
2
[
2], super critical water [3], and metaboric acid [4] have
been deployed for the synthesis of lactams by Beckmann
rearrangement. Ketoximes undergo Beckmann rearrange-
ment by use of chlorosulphonic acid in presence of tolu-
ene with high selectivity [5]. Yang and coworkers have
reported Beckmann rearrangement of ketoximes by use
of an effective and green catalyst, sulfamic acid [6].
Ketoximes undergo Beckmann rearrangement under
very mild condition in presence of 2,4,6-trichloro[1,3,5]-
triazene in DMF at room temperature to form amides
corresponding ketones by reaction with NH OH.HCl in
2
ethanolic NaOH (Scheme 1) [15]. The oximes were char-
1
acterized by their IR, H NMR, and elemental analytical
data (Table 1). (E)-5-oximino-3,4-dihydro-1(2H)-benzox-
epin (2b; X ¼ O, n ¼ 3, R ¼¼ R ¼¼ H) in IR spectrum
1
2
ꢀ
1
exhibited OH band at 3244 cm . In H NMR spectra, a
1
[
7]. Silica-supported MoO has been used as a catalyst
3
multiplet for two protons at C-3 appeared at d 2.00; a
for the Beckmann rearrangement of oximes into
amides [8]. Zhu et al. have used BOP-Cl(tris(2-oxo-3-
oxazolidinyl)phosphinic chloride, the first organophos-
phorous catalyst, for the conversion of ketoximes into
amides by Beckmann rearrangement [9]. Dai and
coworkers have used Grignard reagent for the first
time to induce Beckmann rearrangement directly with-
out any additional protic agents for the synthesis of
multiplet at d 2.85 appeared for 4-CH ; a triplet for OCH2
2
appeared at d 4.25; a multiplet at d 7.6 appeared for 4-
phenyl-H. The elemental analytical data for C, H, and N
obtained for 2b were within þ0.25 range.
Our efforts to study Beckmann rearrangement of
(E)-oximes 2 using InBr resulted in very poor yield of
3
lactam 3 (5–15%). However, we were successful in car-
rying out Beckmann rearrangement of (E)-oximes 2
2-aryl-1-benzazocines [10].
V
C
2011 HeteroCorporation

March 2012
InBr - and AgOTf-Catalyzed Beckmann Rearrangement of (E)-Benzoheterocyclic Oximes
3
425
Scheme 1
Scheme 2
derived from cyclic ketones 1 with InBr and AgOTf in
3
good to excellent yield (Scheme 2).
Thus, the reaction of (E)-oxime derivatives 2 on reac-
tion with a mixture of InBr3 and AgOTf as catalyst
resulted in the formation of rearranged cyclic amide 2,3-
dihydrobenzo[b][1,4]oxazepin-4(5H)-one (3a), 3,4-dihy-
dro-2H-benzo[b][1,4]oxazocin-5(6H)-ones (3b-e), 3,4-
Table 1
Physical and spectral data of heterocyclic (E)-oximes 2a–f [15].
ꢁ
2
a
Compound
Yields
Mp ( C)
Physical/spectral data
8
1%
140
(E)-4-Chromanone oxime (2a): Colorless solid; crystallized from aq.
EtOH; colorless crystals [16].
b
86%
94
(E)-5-Oximino-3,4-dihydro-1(2H)-benzoxepine (2b): Colorless solid;
crystallized from aq. EtOH; colorless crystals [17]; IR (KBr): 512,
6
2
4
56, 750, 826, 972, 1050, 1126, 1203, 1285, 1491, 1606, 2367,
ꢀ1 1
952, 3244 cm ; H NMR: d 2.00 (m, 2H, 3-CH
-CH ), 4.25 (t, 2H, OCH ), 7.6 (m, 4H, phenyl-H); Anal. Calcd.
(177): C, 67.78; H, 6.26; N, 7.90; Found: C,
7.58; H, 6.22; N, 7.86.
2
), 2.85 (m, 2H,
2
2
for C10H11NO
2
6
8
4%
73
(E)-7-Methyl-5-oximino-3,4-dihydro-1(2H)-benzoxepine (2c):
Crystallized from benzene–Hexane; pale yellow crystals [18]; IR
c
(
KBr): 461, 511, 587, 655, 748, 825, 859, 886, 959, 1055, 1079,
1
2
2
125, 1202, 1236, 1284, 1320, 1378, 1412, 1454, 1491, 1605,
ꢀ
1 1
363, 2952, 3244 cm ; H NMR (CDCl
.01 (m, 2H, CH ), 2.31 (s, 3H, CH ), 2.92 (t, 2H, CH
), 6.88 (d, 1H, phenyl-H), 7.08 (m, 1H, phenyl-H),
.28 (d, 1H, phenyl-H); Anal. Calcd. for C11 (191): C,
9.09; H, 6.85; N, 7.32; Found: C, 68.79; H, 6.75; N, 7.21.
3
): d 1.79 (bh, 1H, OH),
2
3
2
), 4.14
(
t, 2H, OCH
2
7
6
H13NO
2
8
8
8%
5%
110
86
(E)-7,8-Dimethyl-5-oximino-3,4-dihydro-1(2H)-benzoxepine (2d):
Crystallized from benzene–Hexane; dark yellow crystals [19].
d
e
(E)-7-Methoxy-5-Oximino-3,4-dihydro-1(2H)-benzoxepine (2e):
Crystallized from benzene–Hexane; pale yellow crystals [20]; IR
(
1
KBr): 512, 588, 749, 826, 969, 1056, 1205, 1283, 1380, 1492,
ꢀ
1 1
606, 2953, 3230 cm ; H NMR (CDCl
.82 (m, 2H, CH ), 3.68 (s, 3H, OCH ), 3.98 (t, 2H, CH
(207): C, 63.76;
3
): d 1.80 (m, 2H, CH
2
),
2
(
2
3
2
), 6.85
m, 3H, phenyl-H) ); Anal. Calcd. for C11
H
13NO
3
H, 6.32; N, 6.76; Found: C, 63.64; H, 6.29; N, 6.73.
8
7%
98
(E)-5-Oximino-3,4-dihydro-1(2H)-benzothiepine (2f): Crystallized
from benzene-Hexane; brown crystals [21]; IR (KBr): 466, 539,
f
6
1
34, 754, 904, 960, 8035, 1087, 1150, 1244, 1300, 1351, 1440,
ꢀ1 1
586, 1628, 1721, 1853, 2368, 2923, 3062, 3250 cm ; H NMR
): d 2.16 (m, 2H, CH ), 2.89–3.01 (m, 4H, CH ),
.17–7.51 (m, 4H, phenyl-H), 8.63 (bh, 1H, OH) ); Anal. Calcd.
11NOS (193): C, 62.15; H, 5.74; N, 7.25; S, 16.59;
Found: C, 61.86; H, 5.71; N, 7.23; S, 16.55.
(
CDCl
3
2
2
7
for C10
H
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

4
26
V. K. Tandon, A. K. Awasthi, H. K. Maurya, and P. Mishra
Vol 49
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

March 2012
InBr - and AgOTf-Catalyzed Beckmann Rearrangement of (E)-Benzoheterocyclic Oximes
3
427
Scheme 3
dihydro-2H-benzo[b][1,4]thiazocin-5(6H)-one (3f), 4,5-
dihydro-1H-benzo[b]azepin-2(3H)-one (3g), and 3,4-
dihydroquinolin-2(1H)-one (3h) in excellent yields
[3] Buero, M.; Ikeshoji, T.; Liew, C. C.; Terakura, K.; Parri-
nello, M. J Am Chem Soc 2004, 126, 6280.
[4] Chandrasekhar, S.; Gopalaiah, K. Tetrahedron Lett 2002, 43,
2455.
(
Scheme 2, Table 2) [22].
Compound 3e in IR spectrum exhibited C ¼¼ O band at
[
5] Li, D.; Shi, F.; Guo, S.; Deng, Y. Tetrahedron Lett 2005,
46, 671.
[6] Wang, B.; Gu, Y.; Luo, C.; Yang, T.; Yang, L.; Suo, J. Tet-
rahedron Lett 2004, 45, 3369.
7] Luca, L. D.; Giacomelli, G.; Porcheddu, A. J Org Chem
000, 67, 6272.
[8] Dongare, M. K.; Bhagwat, V. V.; Ramana, C. V.; Gurjar,
ꢀ ꢀ1
1
1
670 cm and NH at 3240 cm . In H NMR spectra,
1
a singlet at d 1.62 exchangeable with D O appeared for
NH, a multiplet at d 2.01 for CH appeared for 2-pro-
2
[
2
2
tons at C-4. A triplet at 2.37 for 2-protons of CH2
appeared for C-3 and a singlet at d 3.78 for 3-protons
appeared for OMe, a triplet at 4.16 for 2-protons of
M. K. Tetrahedron Lett 2004, 45, 4759.
[9] Zhu, M.; Cha, C.; Deng, W. P.; Shi, X. X. Tetrahedron Lett
2006, 47, 4861.
OCH and two doublets and multiplet for aromatic pro-
2
[
[
[
10] Ma, Z.; Dai, S.; Yu, D. Tetrahedron Lett 2006, 47, 4721.
tons appeared between d 6.59 and 7.09.
The Beckmann rearrangement reaction of (E)-keto
11] Tandon, V. K.; Maurya, H. K. Heterocycle 2009, 77, 611.
12] Barman, D. C.; Thakur, A. J.; Prajapati, D.; Sandhu, J. S.
oximes 2 in presence of InBr /AgOTf is regioselective
Chem Lett 2000, 1196.
3
leading to formation of lactam 3 exclusively. This
became evident by independent synthesis of lactam 3b
from ketone 1b [29]. In presence of AgOTf, indium bro-
mide is converted into indium triflate, the triflate ion
being a better leaving group than bromide ion increases
the rate of the reaction. It is essential to use silvertriflate
as the triflate anion is weakly coordinating, it is useful
[13] Cordero-Vargas, A.; Quiclet-Sire, B.; Zard, S. Z. Bioorg
Med Chem 2006, 14, 6165.
[
14] Perreira, M.; Kim, E. J.; Thomas, C. Z.; Hanover, J. A. Bio-
org Med Chem 2006, 14, 837 and reference 7 cited therein.
15] General method for the synthesis of Oximes (2): A suspen-
[
sion of ketone 1 (0.02 mol) and NH OH.HCl (1.4 g, 0.02 mol) in
2
15 mL of 50% aq. EtOH and NaOH (0.8 g, 0.02 mol) was refluxed for
1 h. Oximes 2 were obtained as solid on cooling and crystallized from
suitable solvent.
þ
as a halide abstraction reagent. The role of Ag is to
facilitate the acceleration of the rate of reaction as AgBr
is precipitated as side product.
[
[
16] Powell, S. G. J Am Chem Soc 1923, 45, 2708.
17] Tandon, V. K.; Khanna, J. M.; Anand, N.; Srimal, R. C.;
Prasad, C. R.; Kar, K. Indian J Chem 1975, 13, 1.
[18] Fontaine, G. Ann Chim (Paris) 1968, 3, 179.
The plausible mechanism of formation of lactam 3
from (E)-ketoxime 2 is exhibited in Scheme 3.
The new route to synthesis of these pharmaceutically
active heterocycles and reactivity of other metal triflates
are being further explored. In summary, we have dem-
[
[
19] Fontaine, G.; Maitte, P. Compt Rend 1964, 258, 4583.
20] Tandon, V. K.; Chandra, A.; Dua, P. R.; Srimal, R. C. Arch
Pharm 1993, 326, 221.
21] Mohrbacher, R. J.; Carson, E. L. U.S. Pat. 3,243,439 ( 1966);
[
Chem Abstr 1966, 64, 19623b.
onstrated InBr - and AgOTf-catalyzed Beckmann rear-
3
[22] General procedure for the Beckmann rearrangement of
oximes (2) to lactams (3): A mixture of oxime 2 (10 mmol), InBr
(
3
rangement of cyclic-(E)-oximes 2 resulting in the forma-
tion of rearranged cyclic amides 3 in excellent yields.
1.5 mmol), AgOTf (4.5 mmol), and acetonitrile (20 mL) was refluxed
ꢁ
under nitrogen at 90 C for 2h. After removal of the solvent, the semi-
solid compound was dissolved in CH Cl (20 mL), extracted with
2
2
Acknowledgments. A.K.A. thanks C.S.T. [CST/SERPD/
water (3 ꢂ 10 mL), brine (10 mL) and dried over Na
2
SO
4
to afford
2
001], Lucknow, India, for Junior Research Fellowship,
semisolid which was crystallized with suitable solvent.
[
[
[
23] Huckle, D.; Lockhart, I. M.; Wright, M. J Chem Soc 1965, 1137.
and H.K.M. acknowledges UGC, New Delhi, India, for
assessment of Senior Research Fellowship.
24] Badilescu, I. I. Rev Roum Chim 1975, 20, 1077.
25] Mohrbacher, R. J. U.S. Pat. 3,311,615 ( 1967);
Chem
Abstr 1967, 67, 43830w.
26] Huckle, D.; Lockhart, I. M.; Webb, N. E. J Chem Soc
971, 2252.
[27] Chen, W. Y.; Gilman, N. W. J Heterocycl Chem 1983, 20, 663.
[
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Journal of Heterocyclic Chemistry
DOI 10.1002/jhet