Cyclic Oxalylation of Primary N-Substituted Anthranilamides: 1H-Benzoe]1, 4]diazepine-2, 3, 5(4H)-triones and 11a-Chlorobenzoe]oxazolo3, 2-a]1, 4]diazepine-2, 3, 5, 11(10H, 11aH)-tetraones

Article abstract of DOI:10.1515/znb-2010-0916

In dependence on the molar ratio, the reaction of primary anthranilamides 3 with oxalyl chloride produced 1H-benzoe]1,4]diazepine-2,3,5(4H)-triones 4 or 10-substituted 11a-chloro-benzoe]-oxazolo3,2-a]1,4]diazepine-2,3,5,11(10H, 11aH)-tetraones 5, the stru

Full text of DOI:10.1515/znb-2010-0916

Cyclic Oxalylation of Primary N-Substituted Anthranilamides:
1H-Benzo[e][1,4]diazepine-2,3,5(4H)-triones and 11a-Chloro-
benzo[e]oxazolo[3,2-a][1,4]diazepine-2,3,5,11(10H,11aH)-tetraones
Maria Anna Ko¨llner and Detlef Geffken
Institute of Pharmacy, University of Hamburg, Bundesstraße 45, 20146 Hamburg, Germany
Reprint requests to Prof. Dr. Detlef Geffken. Fax: +49 40 428383477.
E-mail: geffken@chemie.uni-hamburg.de
Z. Naturforsch. 2010, 65b, 1155 – 1160; received April 9, 2010
Dedicated to Professor Gerwalt Zinner
In dependence on the molar ratio, the reaction of primary anthranilamides 3 with oxalyl chlor-
ide produced 1H-benzo[e][1,4]diazepine-2,3,5(4H)-triones 4 or 10-substituted 11a-chloro-benzo[e]-
oxazolo[3,2-a][1,4]diazepine-2,3,5,11(10H, 11aH)-tetraones 5, the structures of which were unam-
biguously proven by X-ray diffraction analysis.
Key words: Anthranilamides, Cyclization, Fused Heterocycles, Oxalyl Chloride, Acylation
Table 1. 1H-Benzo[e][1,4]diazepine-2,3,5(4H)-triones
4
Introduction
and 11a-chloro-benzo[e]oxazolo[3,2-a][1,4]diazepine-2,3,5,
11(10H, 11aH)-tetraones 5.
The anthranilic scaffold plays an important role as a
pharmacophore and toxophore in medicinal and agri-
cultural chemistry and contributes to a variety of bio-
logical activities [1 – 9]. Although ring-closure reac-
tions of N-unsubstituted anthranilic acid derivates have
been extensively elaborated, investigations towards the
corresponding chemistry of N-alkyl(aryl)-anthranilic
acids remained fragmentary until hitherto.
Entry
R
benzyl
Yield of 4 (%)
Yield of 5 (%)
a
b
c
d
e
f
75
54
60
68
71
59
75
70
87
65
65
67
75
78
4-F-benzyl
4-Br-benzyl
2-phenylethyl
phenyl
methyl
ethyl
g
Recent results from our studies directed to bioac-
tive seven-membered heterocycles with the anthranilic
skeleton disclosed a facile access to novel and stable
1,4-benzodiazepine-triones 1 and 2 by oxalylation of
anthranilic hydroxamates and hydrazides in the pres-
ence of imidazole [10, 11] (Fig. 1).
Results and Discussion
In continuation of our studies on 1,4-benzotri-
azepinetriones we considered the reaction of N-2-
substituted primary anthranilamides 3 with oxalyl
chloride in the presence of imidazole as a base.
We observed the formation of either 4-unsubstit-
uted 1,4-benzodiazepine-triones 4 or 10-substitut-
ed 11a-chloro-benzo[e]oxazolo[3,2-a][1,4]diazepine-
2,3,5,11(10H, 11aH)-tetraones 5, the outcome of the
reaction depending on the molar ratio of the reactants
(Table 1).
When anthanilamides 3a – g were reacted with im-
idazole/oxalyl chloride in anhydrous tetrahydrofuran
in a molar ratio of 1 : 2.2 : 1.1, 1,4-benzodiazepine-
triones 4a – g were obtained exclusively in 54 – 75 %
yield (Scheme 1). Structural assignment is based on
Fig. 1. 4-Alkoxy- and 4-amino-1,4-benzodiazepine-2,3,5-tri-
ones 1 and 2.
1
IR, H NMR, 13C NMR spectra, as well as micro-
analysis. In addition, unambiguous structural proof
c
0932–0776 / 10 / 0900–1155 $ 06.00 ꢀ 2010 Verlag der Zeitschrift fu¨r Naturforschung, Tu¨bingen · http://znaturforsch.com
Brought to you by | Emory University
Authenticated
Download Date | 8/4/15 8:19 AM

1156
M. A. Ko¨llner – D. Geffken · Cyclic Oxalylation of Primary N-Substituted Anthranilamides
Scheme 2. Proposed reaction mechanism
for the conversion of 3 to 5.
Fig. 2 (color online). Molecular structure of 4b in the crystal.
Scheme 1. Cyclic oxalylation of anthranilamides 3 to hetero-
cycles 4 and 5.
tions 5/5A came into consideration for the cycliza-
tion products (Scheme 1). Unambiguous structural
proof was obtained from X-ray diffraction analysis of
5e (Fig. 3), which unveiled a 11a-chloro-10-phenyl-
benzo[e]oxazolo[3,2-a][1,4]diazepine-2,3,5,11(10H,
11aH)-tetraone with covalently bonded chlorine at
C11a, ruling out the possible ionic structure 5A.
As shown by an additional experiment, 4b could
be converted in 81 % yield into 5b with imid-
azole/oxalyl chloride in a molar ratio of 1 : 1 : 1.2,
thus offering a rationale for a plausible reaction mech-
anism for the heterocyclization of 3 to 5 as out-
could be obtained from X-ray diffraction analysis of
4b (Fig. 2).
However, when 3a – g were reacted with imid-
azole/oxalyl chloride in a molar ratio of 1 : 3 : 2.3, crys-
talline compounds resulted with sharp ν(C=O) ab-
sorption bands at 1850, 1800 and 1700 cm−1 in the
IR spectra, and microanalysis data of these compounds
revealed the presence of one chlorine atom, two ox-
alic subunits and one anthranilic skeleton within the
molecules.
On the basis of these surprising results, and tak- lined in Scheme 2: the oxalylation of 3 produces pri-
ing into account literature reports on the oxalylation marily the 1,4-benzodiazepine-trione 4, which takes
of secondary amides [12] and imides [13], constitu- up unconsumed oxalyl chloride to form interme-
Brought to you by | Emory University
Authenticated
Download Date | 8/4/15 8:19 AM

M. A. Ko¨llner – D. Geffken · Cyclic Oxalylation of Primary N-Substituted Anthranilamides
1157
[D6]DMSO): δ = 4.37 (d, J = 5.77 Hz, 2 H, CH2), 6.52 –
7.86 (m, 10 H, Ar-H and NH2), 8.58 (t, J = 5.77 Hz, 1 H,
NH). – 13C NMR (100 MHz, [D6]DMSO): δ = 45.17 (CH2),
111.47, 114.29 (aryl-CH), 115.12 (d, 2JC-F = 20.81 Hz, aryl-
3
CH), 128.85 (aryl-CH), 128.97 (d, JC-F = 8.48 Hz, aryl-
CH), 132.41 (aryl-CH), 135.79 (d, 4JC-F = 3.08 Hz, aryl-C),
1
149.38 (aryl-C), 161.12 (d, JC-F = 242.76 Hz, CF), 171.56
(C=O). – C14H13FN2O (244.26): calcd. C 68.84, H 5.36,
N 11.47; found C 68.84, H 5.53, N 11.47.
2-(4-Bromobenzylamino)benzamide (3c)
◦
Yield: 72 %, m. p. 157 C. – IR (KBr): ν = 3423, 3338
(NH), 1670/1637 cm−1 (C=O). – 1H NMR (400 MHz,
[D6]DMSO): δ = 4.38 (d, J = 5.99 Hz, 2 H, CH2), 6.53 – 7.86
(m, 10 H, Ar-H and NH2), 8.62 (t, J = 5.99 Hz, 1 H, NH). –
13C NMR (100 MHz, [D6]DMSO): δ = 45.19 (CH2), 111.51
(aryl-CH), 114.32 (CBr), 114.36 (aryl-CH), 119.67 (aryl-C),
129.04, 129.17, 131.27, 132.43 (aryl-CH), 139.30, 149.30
(aryl-C), 171.55 (C=O). – C14H13BrN2O (305.17): calcd.
C 55.10, H 4.29, N 9.18; found C 55.04, H 4.48, N 9.16.
Fig. 3 (color online). Molecular structure of 5e in the crystal.
diate 6/6A that finally undergoes ring closure to
form 5.
Conclusion
General procedure for the synthesis of compounds 4a – g
In summary, the cyclic oxalylation of primary an-
thranilamides to 1,4-benzodiazepine-triones 4 or their
oxazolo-condensed derivatives 5, which are character-
ized by an uncommon orthoacetalic (Cl, N, O) func-
tionality at C11a, was investigated. The outcome of the
reactions was found to depend crucially on the molar
ratio of anthanilamide 3, imidazole and oxalyl chlo-
ride.
To a mixture of 3 [14 – 17] (1 mmol) and imidazole
(2.2 mmol) in anhydrous THF (8 mL) was added dropwise
a solution of oxalyl chloride (1.1 mmol) in anhydrous THF
(2 mL) at r. t. The resulting suspension was stirred for an-
other 24 h at ambient temperature and then filtered. After re-
moval of the solvent under reduced pressure the residue was
chromatographed on silica gel with CH2Cl2/Et2O (1 : 1) as
an eluent and crystallized from CH2Cl2/Et2O.
Experimental Section
1-Benzyl-1H-benzo[e][1,4]diazepine-2,3,5(4H)-trione (4a)
IR spectra were obtained on a Varian 800 FT-IR spec-
trometer from KBr pellets. 1H and 13C NMR spectra were
recorded in CDCl3, [D6]DMSO and [D8]THF on a Bruker
AMX 400 spectrometer, with TMS as internal reference. Pu-
rification by column chromatography was carried out with
ICN silica gel 100 – 200 (active, 60 A). Elemental analyses
(C, H, N) were conducted using the Elemental Analyzer Her-
aeus CHN-O-Rapid.
◦
Yield: 75 %, m. p. 143 C. – IR (KBr): ν = 3146 (NH),
1738, 1699, 1665 cm−1 (C=O). – 1H NMR (400 MHz,
CDCl3): δ = 5.23 (s, 2 H, CH2), 7.21 – 7.90 (m, 9 H, Ar-H),
8.51 (s, 1 H, NH). – 13C NMR (100 MHz, CDCl3): δ = 53.33
(CH2), 123.04, 126.78, 127.07 (aryl-CH), 127.21 (aryl-C),
127.93, 128.97, 131.96, 134.08 (aryl-CH), 135.13, 136.74
(aryl-C), 160.18, 161.88, 166.06 (C=O). – C16H12N2O3
(280.29): calcd. C 68.57, H 4.32, N 9.99; found C 68.55,
H 4.33, N 10.00.
˚
General procedure for the synthesis of compounds 3b
and 3c
1-(4-Fluorobenzyl)-1H-benzo[e][1,4]diazepine-2,3,5(4H)-
trione (4b)
Ammonia was slowly bubbled in an ice-cooled solution of
the corresponding isatoic anhydride (14 mmol) in anhydrous
THF (40 mL) until the reaction was complete (DC, IR). After
removal of the solvent under reduced pressure the product
was recrystallized from CH2Cl2/Et2O.
◦
Yield: 54 %, m. p. 137 C. – IR (KBr): ν = 3140 (NH),
1730, 1676, 1664 cm−1 (C=O). – 1H NMR (400 MHz,
[D6]DMSO): δ = 5.22 (s, 2 H, CH2), 7.11 – 7.70 (m,
8 H, Ar-H), 12.17 (s, 1 H, NH). – 13C NMR (100 MHz,
[D6]DMSO): δ = 50.30 (CH2), 115.42 (d, 2JC-F = 21.96 Hz,
2-(4-Fluorobenzylamino)benzamide (3b)
◦
Yield: 63 %, m. p. 136 C. – IR (KBr): ν = 3475, 3326, aryl-CH), 123.43, 126.47 (aryl-CH), 128.64 (aryl-C), 129.19
3178 (NH), 1647 cm−1 (C=O). – 1H NMR (400 MHz, (d, 3JC-F = 8.05 Hz, aryl-CH), 130.62 (aryl-CH), 132.09 (d,
Brought to you by | Emory University
Authenticated
Download Date | 8/4/15 8:19 AM

1158
M. A. Ko¨llner – D. Geffken · Cyclic Oxalylation of Primary N-Substituted Anthranilamides
4JC-F = 3.66 Hz, aryl-C), 133.53 (aryl-CH), 135.51 (aryl-C), 1-Ethyl-1H-benzo[e][1,4]diazepine-2,3,5(4H)-trione (4g)
1
160.81 (C=O), 161.36 (d, JC-F = 242.98 Hz, CF), 163.36,
Yield: 75 %, m. p. 142 ◦C. – IR (KBr): ν = 3148
166.58 (C=O). – C16H11FN2O3 (298.28): calcd. C 64.43,
H 3.72, N 9.39; found C 64.45, H 3.80, N 9.37.
(NH), 1735, 1660 cm−1 (C=O). – 1H NMR (400 MHz,
[D6]DMSO): δ = 1.17 (t, 3H, J = 7.02 Hz, CH2CH3), 4.01
(q, 2 H, J = 7.02 Hz, CH2CH3), 7.41 – 7.74 (m, 4 H, Ar-H),
1-(4-Bromobenzyl)-1H-benzo[e][1,4]diazepine-2,3,5(4H)-
12.12 (s, 1 H, NH). – 13C NMR (100 MHz, [D6]DMSO):
trione (4c)
δ = 12.56 (CH3), 43.53 (CH2), 123.29, 126.38 (aryl-CH),
◦
128.69 (aryl-C), 130.59, 133.68 (aryl-CH), 135.65 (aryl-C),
160.25, 163.89, 166.76 (C=O). – C11H10N2O3 (218.07):
calcd. C 60.55, H 4.62, N 12.84; found C 60.31, H 4.69,
N 12.73.
Yield: 60 %, m. p. 214 C. – IR (KBr): ν = 3125 (NH),
1745, 1665 cm−1 (C=O). – 1H NMR (400 MHz, [D8]THF):
δ = 5.23 (s, 2 H, CH2), 7.22 – 7.83 (m, 8 H, Ar-H), 11.04
(s, 1 H, NH). – 13C NMR (100.61 MHz, [D8]THF): δ =
51.15 (CH2), 121.00 (aryl-C), 122.80, 125.87 (aryl-CH),
128.62 (aryl-C), 129.08, 131.28, 131.60, 133.11 (aryl-CH),
135.88, 136.84 (aryl-C), 160.69, 162.37, 165.99 (C=O). –
C16H11BrN2O3 (359.17): calcd. C 53.50, H 3.09, N 7.80;
found C 53.29, H 3.15, N 7.61.
General procedure for the synthesis of compounds 5a – g
To a mixture of 3 [14 – 17] (1 mmol) and imidazole
(3 mmol) in anhydrous THF (8 mL) was added dropwise a
solution of oxalyl chloride (2.3 mmol) in anhydrous THF
(2 mL) at r. t. The resulting suspension was stirred for an-
other 24 h at ambient temperature and then filtered. After re-
moval of the solvent under reduced pressure the residue was
chromatographed on silica gel with CH2Cl2/Et2O (95 : 5) as
an eluent and crystallized from CH2Cl2/Et2O.
1-Phenylethyl-1H-benzo[e][1,4]diazepine-2,3,5(4H)-trione
(4d)
◦
Yield: 68 %, m. p. 178 C. – IR (KBr): ν = 3180 (NH),
1720, 1700, 1676 cm−1 (C=O). – 1H NMR (400 MHz,
CDCl3): δ = 2.97 (t, 2 H, J = 7.25 Hz, CH2Ph), 4.34 (t,
2 H, J = 7.25, CH2N), 7.07 – 7.85 (m, 9 H, Ar-H), 8.64
(s, 1 H, NH). – 13C NMR (100 MHz, CDCl3): δ = 33.33
(CH2Ph), 50.39 (CH2N), 123.24, 126.76, 126.94 (aryl-C),
127.72 (aryl-C), 128.60, 128.81, 131.89, 134.09 (aryl-CH),
136.41, 137.10 (aryl-C), 159.77, 161.90, 165.62 (C=O). –
C17H14N2O3 (294.31): calcd. C 69.38, H 4.79, N 9.52; found
C 69.24, H 4.83, N 9.49.
10-Benzyl-11a-chlorobenzo[e]oxazolo[3,2-a][1,4]-
diazepine-2,3,5,11(10H, 11aH)-tetraone (5a)
◦
Yield: 70 %, m. p. 130 C. – IR (KBr): ν = 1846, 1802,
1
1701 cm−1 (C=O). – H NMR (400 MHz, [D8]THF): δ =
5.24 (d, J = 15.77 Hz, 1 H, alkyl CH), 5.35 (d, J = 15.76 Hz,
1 H, alkyl CH), 7.23 – 7.85 (m, 9 H, Ar-H). – 13C NMR
(100.61 MHz, [D8]THF): δ = 52.69 (CH2), 122.57, 126.82,
127.01, 127.38 (aryl-CH), 127.98 (aryl-C), 128.51, 131.28,
134.59 (aryl-CH), 136.12, 138.62 (aryl-C), 147.88, 151.54,
159.39, 160.66 (C=O). – C18H11ClN2O5 (370.75): calcd.
C 58.31, H 2.99, Cl 9.56, N 7.56; found C 58.27, H 3.16,
Cl 9.68, N 7.54.
1-Phenyl-1H-benzo[e][1,4]diazepine-2,3,5(4H)-trione (4e)
◦
Yield: 71 %, m. p. 200 C. – IR (KBr): ν = 3144 (NH),
1733, 1668 cm−1 (C=O). – 1H NMR (400 MHz, CDCl3):
δ = 6.85 – 7.99 (m, 9 H, Ar-H), 8.79 (s, 1 H, NH). – 13C NMR
(100 MHz, CDCl3): δ = 125.63, 126.38 (aryl-CH), 126.46
(aryl-C), 128.17, 128.67, 129.92, 132.00, 133.91 (aryl-CH),
137.69, 139.93 (aryl-C), 159.28, 161.87, 165.99 (C=O). –
C15H10N2O3 (266.26): calcd. C 67.67, H 3.79, N 10.52;
found C 67.39, H 3.76, N 10.40.
11a-Chloro-10-(4-fluorobenzyl)benzo[e]oxazolo[3,2-a]-
[1,4]diazepine-2,3,5,11(10H, 11aH)-tetraone (5b)
Yield: 87 %, m. p. 133 ◦C. – IR (KBr): ν = 1844,
1809, 1715, 1698 cm−1 (C=O). – 1H NMR (400.14 MHz,
[D8]THF): δ = 5.18 (d, J = 15.45 Hz, 1 H, alkyl CH),
5.39 (d, J = 15.77 Hz, 1 H, alkyl CH), 7.02 – 7.86 (m, 8 H,
1-Methyl-1H-benzo[e][1,4]diazepine-2,3,5(4H)-trione (4f)
Yield: 59 %, m. p. 199 ◦C. – IR (KBr): ν = 3184 Ar-H). – 13C NMR (100.61 MHz, [D8]THF): δ = 51.89
2
(NH), 1707, 1665 cm−1 (C=O). – 1H NMR (400 MHz, (CH2), 96.84 (CCl), 115.30 (d, JC-F = 22.00 Hz, aryl-
[D6]DMSO): δ = 3.42 (s, 3 H, CH3), 7.38 – 7.75 (m, CH), 122.65, 126.95 (aryl-CH), 128.11 (aryl-C), 129.21 (d,
4 H, Ar-H), 12.08 (s, 1 H, NH). – 13C NMR (100 MHz, 3JC-F = 8.25 Hz, aryl-CH), 131.32 (aryl-CH), 132.09 (d,
[D6]DMSO): δ = 36.16 (CH3), 122.99, 125.95 (aryl-CH), 4JC-F = 2.75 Hz, aryl-C), 134.62 (aryl-CH), 138.36 (aryl-C),
1
127.39 (aryl-C), 130.41, 133.58 (aryl-CH), 137.16 (aryl- 147.86, 151.49, 159.36, 160.62 (C=O), 162.22 (d, JC-F
=
C), 160.37, 162.99, 166.54 (C=O). – C10H8N2O3 (204.18): 245.61, CF). – C18H10ClFN2O5 (388.74): calcd. C 55.61,
calcd C 58.82, H 3.95, N 13.72; found C 58.78, H 4.02, H 2.59, Cl 9.12, N 7.21; found C 55.53, H 2.78, Cl 8.99,
N 13.67.
N 7.14.
Brought to you by | Emory University
Authenticated
Download Date | 8/4/15 8:19 AM

M. A. Ko¨llner – D. Geffken · Cyclic Oxalylation of Primary N-Substituted Anthranilamides
1159
10-(4-Bromobenzyl)-11a-chlorobenzo[e]oxazolo[3,2-a]-
11a-Chloro-10-ethylbenzo[e]oxazolo[3,2-a][1,4]diazepine-
[1,4]diazepine-2,3,5,11(10H, 11aH)-tetraone (5c)
2,3,5,11(10H, 11aH)-tetraone (5g)
Yield: 65 %, m. p. 146 ◦C. – IR (KBr): ν = 1848,
1801, 1709 cm−1 (C=O). – 1H NMR (400, [D8]THF):
δ = 5.18 (d, J = 15.77 Hz, 2 H, alkyl CH), 5.34 (d,
J = 15.76 Hz, 2 H, alkyl CH), 7.17 – 7.87 (m, 8 H,
Ar-H). – 13C NMR (100 MHz, [D8]THF): δ = 52.06 (CH2),
96.81 (CCl), 121.25 (aryl-C), 122.49, 126.97 (aryl-CH),
128.00 (aryl-C), 129.13 (aryl-CH), 131.36 (aryl-C), 131.67,
134.67, 135.44 (aryl-CH), 138.38 (aryl-C), 147.84, 151.46,
159.38, 160.61 (C=O). – C18H10BrClN2O5 (449.64): calcd.
C 48.08, H 2.24, Cl 7.88, N 6.23; found C 48.00, H 2.48, Cl
7.69, N 6.15.
Yield: 78 %, m. p. 141 ◦C. – IR (KBr): ν = 1844,
1805, 1686 cm−1 (C=O).
–
1H NMR (400 MHz,
[D8]THF): δ = 1.22 (t, J = 7.1 Hz, 3 H, CH2CH3),
3.90 – 4.25 (m, 2 H, CH2CH3), 7.45 – 7.86 (m, 4 H,
Ar-H). – 13C NMR (100 MHz, [D8]THF): δ = 12.22
(CH2CH3), 45.25 (CH2CH3), 96.76 (CCl), 122.58, 126.76
(aryl-CH), 128.11 (aryl-C), 131.29, 134.78 (aryl-CH),
138.63 (aryl-C), 147.92, 151.67, 158.69, 160.80 (C=O). –
C13H9ClN2O5 (308.68): calcd. C 50.58, H 2.94, Cl
11.49,
N 9.08; found C 50.30, H 3.10, Cl 11.23,
N 8.99.
11a-Chloro-10-phenylethylbenzo[e]oxazolo[3,2-a][1,4]-
diazepine-2,3,5,11(10H, 11aH)-tetraone (5d)
Conversion of 4b to 5b
To a mixture of 4b (1 mmol) and imidazole (1 mmol) in
anhydrous THF (8 mL) was added dropwise a solution of ox-
alyl chloride (1.2 mmol) in anhydrous THF (2 mL) at r. t. The
resulting suspension was stirred for another 24 h at ambient
temperature and then filtered. After removal of the solvent
under reduced pressure the residue was chromatographed on
silica gel with CH2Cl2/Et2O (95 : 5) as an eluent to give 5b
in 81 % yield.
◦
Yield: 65 %, m. p. 144 C. – IR (KBr): ν = 1846, 1803,
1708 cm−1 (C=O). – 1H NMR (400 MHz, [D8]THF):
δ = 2.90 – 3.00 (m, 2 H, CH2Ph), 4.07 – 4.60 (m, 2 H,
CH2N), 7.13 – 7.86 (m, 9 H, Ar-H). – 13C NMR (100 MHz,
[D8]THF): δ = 33.29 (CH2Ph), 51.43 (CH2N), 96.69 (CCl),
123.04, 126.43, 126.82 (aryl-CH), 128.22 (aryl-C), 128.43,
128.46, 131.27, 134.73 (aryl-CH), 137.87, 138.75 (aryl-C),
147.75, 151.53, 159.01, 160.48 (C=O). – C19H13ClN2O5
(384.78): calcd. C 59.31, H 3.41, Cl 9.21, N 7.28; found
C 59.35, H 3.46, Cl 9.46, N 7.26.
Crystal structure determinations
Crystal data for 4b: C16H11FN2O3, Mr = 298.27, 0.31 ×
0.14 × 0.07 mm3, MoKα radiation, λ = 0.71073 A, mono-
˚
11a-Chloro-10-phenylbenzo[e]oxazolo[3,2-a][1,4]-
diazepine-2,3,5,11(10H, 11aH)-tetraone (5e)
clinic, space group C2/c, a =◦22.059 (7), b = 15.659 (5), c =
3
˚
˚
7.753 (2) A, β = 99.267 (4) , V = 2643.0 (14) A , Z = 8,
Dcalcd. = 1.50 Mg m−3, µ(MoKα ) = 0.1 mm−1, F(000) =
1232 e, T = 100 K, θ = 1.2 – 28.5◦, h = −27 → 28, k =
−13 → 20, l = 9, 8577 measured reflections, 2974 inde-
pendent reflections, Rint = 0.028, R[F2 ≥ 2 σ(F2)] = 0.040,
wR(F2) = 0.100 (all data) for 200 refined parameters, S =
◦
Yield: 67 %, m. p. 141 C. – IR (KBr): ν = 1849, 1805,
1
1705 cm−1 (C=O). – H NMR (400 MHz, [D8]THF): δ =
6.96 – 6.98 (m, 1 H, Ar-H), 7.39 – 7.62 (m, 7 H, Ar-H), 7.97 –
7.99 (m, 1 H, Ar-H). – 13C NMR (100 MHz, [D8]THF):
δ = 96.94 (CCl), 125.10, 126.56 (aryl-CH), 127.44 (aryl-C),
128.12, 128.40, 129.32, 131.39, 134.50 (aryl-CH), 139.65,
140.82 (aryl-C), 147.91, 151.50, 158.44, 160.63 (C=O). –
C17H9ClN2O5 (356.02): calcd. C 57.24, H 2.54, Cl 9.94,
N 7.85; found C 57.10, H 2.71, Cl 9.67, N 7.83.
−3
˚
1.03, ∆ρmax = 0.31 e A
.
Crystal data for 5e: C17H9ClN2O5, Mr = 356.71, 0.50 ×
0.48 × 0.05 mm3, MoKα radiation, λ = 0.71073 A, triclinic
˚
¯
space group P1, a = 11.662 (4), b = 12.066◦(4), c = 12.349
◦
˚
(4)◦A, α = 90.154 (6) , β = 104.391 (6) , γ = 111.894
11a-Chloro-10-methylbenzo[e]oxazolo[3,2-a][1,4]-
diazepine-2,3,5,11(10H, 11aH)-tetraone (5f)
(5) , V = 1552.9 (10) A , Z = 4, Dcalcd. = 1.53 Mg m−3
,
3
˚
µ(MoKα ) = 0.3 mm−1, F(000) = 728 e, T = 153 K, h = 13,
k = 14, l = 14, 15443 measured reflections, 5458 inde-
pendent reflections, Rint = 0.079, R[F2 ≥ 2 σ(F2)] = 0.044,
wR(F2) = 0.082 (all data) for 451 refined parameters, S =
◦
Yield: 75 %, m. p. 156 C. – IR (KBr): ν = 1842, 1803,
1690 cm−1 (C=O). – 1H NMR (400 MHz, [D8]THF):
δ = 3.52 (s, 3 H, CH3), 7.47 – 7.92 (m, 4 H, Ar-H). –
13C NMR (100 MHz, [D8]THF): δ = 36.76 (CH3), 96.69
(CCl), 122.06, 126.39 (aryl-CH), 126.98 (aryl-C), 131.17,
−3
˚
0.86, ∆ρmax = 0.32 e A
.
CCDC 763443 (4b) and 659167 (5e) contain the supple-
134.75 (aryl-CH), 139.93 (aryl-C), 147.95, 151.61, 159.44, mentary crystallographic data for this paper. These data can
160.68 (C=O). – C12H7ClN2O5 (294.65): calcd. C 48.92, be obtained free of charge from The Cambridge Crystallo-
H 2.39, Cl 12.03, N 9.51; found C 48.85, H 2.43, Cl 11.88, graphic Data Centre via www.ccdc.cam.ac.uk/data request
N 9.49.
/cif.
Brought to you by | Emory University
Authenticated
Download Date | 8/4/15 8:19 AM

1160
M. A. Ko¨llner – D. Geffken · Cyclic Oxalylation of Primary N-Substituted Anthranilamides
Acknowledgements
The authors are indebted to Prof. J. Kopf and Miss
I. Nevoigt for performing the X-ray diffraction analyses,
and Dr. Th. Hackl for NMR measurements and valuable
discussions.
[1] R. Hatley, A. M. Mason, I. L. Pinto, I. E. D. Smith, WO
2006085112, 2006.
Loury, D. C. Griffith, M. N. Dudley, Bioorg. Med.
Chem. Lett. 2007, 17, 2802.
[9] N. R. El-Brollosy, J. Heterocycl. Chem. 2006, 43, 1435.
[10] D. Geffken, M. A. Ko¨llner, Z. Naturforsch. 2005, 60b,
337.
[2] K.-H. Altmann, G. Bold, P. Furet, P. W. Manley, J. M.
Wood, S. Ferrari, F. Hofmann, J. Mestan, A. Huth,
M. Kru¨ger, D. Seidelmann, A. Menrad, M. Haberey,
K.-H. Thierauch, WO 2000027820, 2000.
[11] D. Geffken, M. A. Ko¨llner, Z. Naturforsch. 2005, 60b,
´
[3] J. Fensholdt, J. Thorhauge, B. Nørremark, WO
1207.
2005054179, 2005.
[12] a) T. Sasaki, S. Eguchi, T. Toru, Tetrahedron 1969,
25, 2909; b) R. D. Larsen, R. A. Reamer, E. G. Corley,
P. Davis, E. J. J. Grabowski, P. J. Reider, I. Shinkai, J.
Org. Chem. 1991, 56, 6034; c) R. Suau, J. M. Lopez-
Romero, R. Rico, Tetrahedron Lett. 1996, 52, 9357;
d) J. Bergmann, C. Stalhanske, Tetrahedron 1996, 52,
753; e) F. Chan, P. Magnus, E. G. McIver, Tetrahedron
Lett. 2000, 41, 835.
[13] a) R. Richter, G. H. Temme, J. Org. Chem. 1981, 46,
3015; b) D. Steffek, R. C. Mebane, G. B. Schuster, J.
Org. Chem. 1983, 48, 2619.
[14] A. Tsuji, T. Yamana, Y. Mizukami, Chem. Pharm. Bull.
1974, 22, 623.
[15] N. Hirose, S. Kuriyama, S. Sohda, K. Sakaguchi,
H. Yamamoto, Chem. Pharm. Bull. 1973, 21, 1005.
[16] N. D. Heindel, W. P. Fives, T. F. Lemke, R. A. Carrano,
J. Pharm. Sci. 1971, 60, 703.
[17] V. Bertini, F. Buffoni, G. Ignesti, N. Picci, S. Trombino,
F. Iemma, S. Alfei, M. Pocci, F. Lucchesini, A. De
Munno, J. Med. Chem. 2005, 48, 664.
[4] A. Thorarensen, B. D. Wakefield, D. L. Romero, K. R.
Marotti, M. T. Sweeney, G. E. Zurenko, D. C. Rohrer,
F. Han, Jr., G. L. Bryant, Bioorg. Med. Chem. Lett.
2007, 17, 2823.
[5] S. D. Larsen, M. R. Hester, J. C. Ruble, G. M. Kami-
lar, D. L. Romero, B. Wakefield, E. P. Melchior, M. T.
Sweeney, K. R. Marotti, Bioorg. Med. Chem. Lett.
2006, 16, 6173.
[6] S. Peukert, J. Brendel, B. Pirard, C. Stru¨bing, H.-W.
Kleemann, T. Bo¨hme, H. Hemmerle, Bioorg. Med.
Chem. Lett. 2004, 14, 2823.
[7] G. P. Lahm, T. P. Selby, J. H. Freudenberger, T. M.
Stevenson, B. J. Myers, G. Seburyamo, B. K. Smith,
L. Flexner, C. E. Clark, D. Cordova, Bioorg. Med.
Chem. Lett. 2005, 15, 4898.
[8] W. J. Watkins, L. Chong, A. Cho, R. Hilgenkamp,
M. Ludwikow, N. Garizi, N. Iqbal, J. Barnard,
R. Singh, D. Madsen, K. Lolans, O. Lomovskaya,
U. Oza, P. Kumaraswamy, A. Blecken, S. Bai, D. J.
Brought to you by | Emory University
Authenticated
Download Date | 8/4/15 8:19 AM