Synthesis of 1,4-dialkyl-1,4-dihydro-1,4-benzo[e]diazepine-5-ones

Article abstract of DOI:10.1055/s-2000-6252

The title heterocycles were synthesized by the reaction of N- alkylisatoic anhydrides with N-alkylaminoacetaldehyde dialkyl-acetals, followed by hydrolysis with Amberlyst-15 and dehydration.

Full text of DOI:10.1055/s-2000-6252

PAPER
265
Synthesis of 1,4-Dialkyl-1,4-dihydro-1,4-benzo[e]diazepine-5-ones
Tiansheng Wang*1 Ian S. Cloudsdale2
Novartis Crop Protection, Palo Alto Research Center, 975 California Ave., Palo Alto, CA 94304, USA
Fax +1(781)2751127; E-mail: twang@nitromed.com
Received 2 June 1999; revised 1 October 1999
R1
NH
Abstract: The title heterocycles were synthesized by the reaction of
N-alkylisatoic anhydrides with N-alkylaminoacetaldehyde dialkyl-
acetals, followed by hydrolysis with Amberlyst-15 and dehydra-
tion.
OCH3
OCH3
N
CH3
O
R1 = CH3 (2a), allyl (2b), benzyl
R1
N
a
Key words: bicyclic compounds, benzodiazepines, condensation,
heterocycles, hydrolyses, Amberlyst-15
(2c)
CH3NHCH2CH(OCH3)2
O
+
O
R1
O
or PhCH2NHCH2CH(OCH2CH3)2
b
NH
OC2H5
N
OC2H5
CH2Ph
Since the introduction of 1,4-benzodiazepines as tranquil-
izer drugs in early 1960s,3 synthesis of molecules bearing
a 1,4-benzodiazepine pharmacophore unit has become in-
creasingly important in the pharmaceutical industry. Syn-
thesis of different analogs of 1,4-benzodiazepines has
been well documented.4,5 During the course of our re-
search, we became interested in the preparation of 1,4-
benzodiazepine 1, in which 1- and 4-nitrogens are con-
nected by an unsubstituted 2,3-carbon-carbon double
bond. Only one analog of 1 has been reported in the liter-
ature: it was claimed that the reaction of N-benzylamino
benzamide with 2-bromoacetaldehyde diethyl acetal un-
der basic condition (sodium amide, toluene)6a afforded 1
(R1 = benzyl, R2 = H). However, no mass spectral data
were recorded in the report.6 To the best of our knowl-
edge, 1,4-dialkyl version of 1 has not been reported. Here
we wish to report a novel, simple synthetic route to 1,4-
dialkyl version of 1, namely 1,4-dialkyl-1,4-dihydro-1,4-
benzo[e]diazepine-5-ones 1a-f.
O
R
1 = CH3 (2d), allyl (2e), benzyl (2f)
R1
R1
R1
OH
OR3
R2
N
N
d
N
c
+
2a-2f
N
N
N
R2
O
R2
O
O
1a-1f
4 (R3 = methyl for a-c;
ethyl for d-f)
3 a-f
Reagents and conditions: a) MeCN, reflux, 2 h, 99-100%; b) DMF,
reflux, 1 h, 34-64%; c) Amberlyst-15, THF/H O, r.t., 2-12 h;
2
d) toluene, reflux, Dean-Stark trap, 48-83% over 2 steps.
Scheme
as a catalyst at room temperature afforded polar crude hy-
drolyzed products as an inseparable mixture of hemiami-
nal 3 and methyl or ethyl aminal 4. The structures of
intermediates 3a and 4a were confirmed by mass spectral
analysis of the crude mixture [for 3a (M + 1) = 207 while
4a (M + 1) = 221]. This mixture was then refluxed in tol-
uene with a Dean-Stark trap to generate the benzodiaz-
epines 1a-f (Scheme). The products 1a,b,d,e were
isolated as oils while 1c and 1f as solids. The two enamide
vinyl protons of 1a-f consistently showed two doublets in
the range of 5.28-5.36 and 5.55-5.62 ppm, with a cou-
pling constant of 5.6 Hz.
R1
R2 = CH3, R1 = CH3 (1a), allyl (1b), benzyl (1c);
R2 = benzyl, R1 = CH3 (1d), allyl (1e), benzyl (1f))
N
N
R2
O
1
Refluxing equimolar amounts of N-methylaminoacetalde-
hyde dimethylacetal and N-alkyl (methyl, allyl and ben-
zyl) isatoic anhydride in acetonitrile afforded the amide
products 2-alkylamino-N-methyl-N-(2,2-dimethoxyeth-
yl)benzamides 2a-c as a single product in quantitative
yields (Scheme).7 The reaction of the more hindered
N-benzylaminoacetaldehyde diethylacetal with N-alkyl
isatoic anhydride required refluxing in DMF. The corre-
sponding benzamides 2d-f were isolated after chromato-
graphic purification.
In conclusion, a novel and simple procedure for the prep-
arations of 1,4-dialkyl-1,4-dihydro-1,4-benzo[e]diaz-
epine-5-ones 1a-f has been completed.
Reagents and solvents were used as received from commercial sup-
pliers. TLC was performed on pre-coated Silica Gel 60 F254 plates
form Merck using reagent-grade solvents. Flash chromatography
was performed using Merck silica gel 60 (230-400 mesh). 1H NMR
were performed at 300 MHz and 13C NMR at 75 MHz in CDCl3 un-
less otherwise specified. Chemical shifts are in ppm downfield from
internal TMS. IR spectra were recorded on a Perkin-Elmer 1600 FT
IR spectrometer. Mass spectra were recorded on a HP 5989B spec-
Hydrolysis of the acetal groups of benzamides 2a-f in
aqueous tetrahydrofuran in the presence of Amberlyst-15
Synthesis 2000, No. 2, 265–268 ISSN 0039-7881 © Thieme Stuttgart · New York

266
T. Wang, S. Cloudsdale
PAPER
trometer. HRMS were performed by Mass Spectrometry Facility of
University of California, Berkeley. Elemental analyses were con-
ducted by Galbraith Laboratories, Inc.
2-Alkylamino-N-benzyl-N-(2,2-diethoxyethyl)benzamides 2d-f;
General Procedure
A mixture of N-alkylisatoic anhydride (10 mmol) and N-benzylami-
noacetaldehyde diethylacetal (2.32 g, 10 mmol) in DMF (5 mL) was
heated at the reflux temperature for 1 h. After cooling and evapora-
tion of DMF under vacuum, the residue was flash chromatographed
on silica gel, eluting with 3:1 to 1:1 hexane/Et2O to afford 2d-e.
2-Alkylamino-N-methyl-N-(2,2-dimethoxyethyl)benzamides
2a-c; General Procedure
N-Alkylisatoic anhydride (10 mmol) and N-methylaminoacetalde-
hyde dimethyl acetal (1.192 g, 10 mmol) were mixed in MeCN (10
mL) and the resulting mixture was heated at reflux for 2 h. Cooling
and evaporation gave the oily residue as pure products 2a-c, as con-
2d
Yield: 64%; TLC (silica gel, hexane/Et2O, 1:1); Rf 0.33.
1
1H NMR (300 MHz, CDCl3): d = 1.20 (t, J = 6.4 Hz, 6 H), 2.84 (d,
J = 4.8 Hz, 3 H), 3.46 (br s, 4 H), 3.67 (br s, 2 H), 4.72 (br s, 3 H),
4.94 (br s, 1 H), 6.64 (t, J = 7.5 Hz, 1 H), 6.66 (d, J = 8.5 Hz, 1 H),
7.13-7.34 (m, 7 H).
firmed by TLC and H NMR analysis, in quantitative yield. The
NMR data for 2a-f were broad due to rotamer interconversion.8
The elemental analysis samples were obtained by simple flash chro-
matographic purification on silica gel (hexane/EtOAc, 2:1).
13C NMR (75 MHz, CDCl3) d = 15.23, 30.17, 63.05, 101.02,
110.62, 115.81, 120.18, 127.28, 127.32, 127.59, 128.53, 130.69,
137.06, 147.04, 171.89.
2a
Yield: 99%; TLC (silica gel, hexane /Et2O, 1:1); Rf 0.18.
1H NMR (300 MHz, CDCl3): d = 2.70 (s, 3 H), 2.94 (s, 3 H), 3.26
(br s, 6 H) 3.58 (br s, 2 H), 4.60 (br s, 1 H), 4.97 (br s, 1 H), 6.64-
6.68 (m, 2 H), 7.10 (dd, J = 7.7, 1.6 Hz, 1 H), 7.26 (td, J = 7.8, 1.5
Hz, 1 H).
IR (film): n = 3388, 2974, 2929, 1626, 1604, 1581, 1514, 1455,
1412, 1316, 1240, 1170, 1121, 1061, 976, 749, 699 cm-1.
MS (EI): m/z (%) = 357 (M + 1, 6), 356 (M, 23), 103 (100).
13C NMR (75 MHz, CDCl3): d = 30.15, 54.40, 102.77, 110.63,
115.61, 119.95, 127.54, 130.70, 147.22, 171.60.
Anal. Calcd for C21H28N2O3: C, 70.76; H, 7.92; N, 7.86. Found: C,
70.53; H, 7.95; N, 7.82.
IR (film): n = 3394, 2935, 2832, 1626, 1581, 1515, 1489, 1461,
2e
1426, 1396, 1316, 1293, 1171, 1127, 1103, 1078, 980, 751 cm-1.
Yield: 56%; TLC (silica gel, hexane/Et2O, 1:1); Rf 0.33.
MS (EI): m/z (%) = 253 (M + 1, 9), 252 (M, 48), 134 (100).
1H NMR (300 MHz, CDCl3) d = 1.20 (t, J = 6.0 Hz, 6 H), 3.48 (br
s, 4 H), 3.68 (br s, 2 H), 3.79 (br s, 2 H), 4.73 (br s, 3 H), 5.13 (br s,
1 H), 5.16 (dd, J = 10.3, 1.4 Hz, 1 H), 5.28 (dd, J = 17.2, 1.4 Hz, 1
H), 5.86-5.95 (m, 1 H), 6.64 (t, J = 7.4 Hz, 1 H), 6.66 (d, J = 8.0
Hz, 1 H), 7.14-7.33 (m, 7 H).
13C NMR (75 MHz, CDCl3) d = 15.26, 45.87, 63.14, 101.11, 111.52
116.02, 116.15, 120.44, 127.36, 127.61, 128.54, 130.55, 134.95,
137.05, 145.73, 171.83 (one aromatic carbon is missing due to over-
lapping).
Anal. Calcd for C13H20N2O3: C, 61.88; H, 7.99; N, 11.10. Found: C,
62.06; H, 8.00; N, 10.96.
2b
Yield: 100%; TLC (silica gel, hexane/Et2O, 1:1); Rf 0.32.
1H NMR (300 MHz, CDCl3): d = 3.07 (s, 3 H), 3.38 (br s, 6 H), 3.59
(br s, 2 H), 3.78 (d, J = 5.2 Hz, 2 H), 4.61 (br s, 1 H), 5.10 (br s, 1
H), 5.15 (dq, J = 10.3, 1.5 Hz, 1 H), 5.28 (dq, J = 17.1, 1.6 Hz, 1 H),
5.86-5.99 (m, 1 H), 6.66 (d, J = 7.9 Hz, 1 H), 6.67 (t, J = 7.8 Hz, 1
H), 7.10 (dd, J = 7.9, 1.6 Hz, 1 H), 7.22 (td, J = 7.8, 1.6 Hz, 1 H).
13C NMR (75 MHz, CDCl3): d = 45.90, 54.46, 102.78, 111.48,
115.94, 116.03, 120.21, 127.65, 130.55, 134.96, 145.91, 171.53.
IR (film): n = 3377, 3064, 3029, 2975, 2929, 2880, 1627, 1597,
1582, 1513, 1454, 1413, 1374, 1318, 1292, 1262, 1231, 1123, 1062,
993, 921, 750, 700 cm-1.
MS (EI): m/z (%) = 383 (M + 1, 5), 382 (M, 17), 103 (100).
IR (film): n = 3382, 3078, 2935, 2834, 1626, 1582, 1514, 1488,
1455, 1397, 1318, 1292, 1204, 1165, 1127, 1074, 980, 920,
751 cm-1.
2f
Yield: 34%; mp 77-78°C (Et2O/hexane); TLC (silica gel, hexane/
Et2O, 1:1); Rf 0.44.
1H NMR (300 MHz, CDCl3) d = 1.18 (t, J = 6.7 Hz, 6 H), 3.48 (br
s, 4 H), 3.65 (br s, 2 H), 4.37 (d, J = 5.0 Hz, 2 H), 4.75 (br s, 3 H),
5.45 (br s, 1 H), 6.63 (d, J = 8.9 Hz, 1 H), 6.65 (t, J = 8.3 Hz, 1 H),
7.14-7.41 (m, 12 H).
MS (EI): m/z (%) = 279 (M + 1, 16), 278 (M, 72), 160 (100).
Anal. Calcd for: C15H22N2O3: C, 64.73; H, 7.97; N, 10.06. Found:
C, 64.59; H, 7.96; N, 9.92.
2c
13C NMR (75 MHz, CDCl3) d = 15.26, 47.58, 63.18, 101.17, 111.64
116.30, 120.44, 127.02, 127.15, 127.38, 127.58, 128.51, 128.55,
130.62, 137.02, 139.08, 145.80, 171.85, (one aromatic carbon sig-
nal is missing due to overlapping).
Yield: 99%; TLC (silica gel, hexane/Et2O, 1:1); Rf 0.22.
1H NMR (300 MHz, CDCl3): d = 3.06 (s, 3 H), 3.31 (s, 6 H), 3.59
(br s, 2 H), 4.32 (d, J = 3.5 Hz, 2 H), 4.57 (br s, 1 H), 5.40 (br s, 1
H), 6.61 (d, J = 8.3 Hz, 1 H), 6.65 (t, J = 7.5 Hz, 1 H), 7.10-7.35
(m, 7 H).
13C NMR (75 MHz, CDCl3): d = 38.31 (br), 47.58, 49.88 (br),
54.40, 102.70, 111.59, 116.10, 120.32, 127.01, 127.16, 127.66,
128.50, 130.62, 139.10, 145.89, 171.49.
IR (film): n = 3381, 3028, 2974, 2928, 2880, 1627, 1596, 1582,
1513, 1496, 1452, 1413, 1374, 1322, 1295, 1231, 1126, 1064, 977,
750, 698 cm-1.
MS (EI): m/z (%) = 433 (M + 1, 4), 432 (M, 14), 103 (100).
IR (film): n = 3382, 3062, 3028, 2935, 2834, 1780, 1729, 1633,
1585, 1514, 1494, 1454, 1395, 1322, 1295, 1202, 1165, 1125, 1073,
1028, 981, 943, 920, 817, 750, 699 cm-1.
1,4-Dialkyl-1,4-benzodiazepine-5-ones 1a-f; General Proce-
dure
To a stirred solution of 2 (1-2 mmol) in THF (3 mL) and H2O (0.5
mL) was added Amberlyst-15 (0.5 g, Aldrich) at r.t. After the start-
ing material was consumed (TLC analysis, for 2a-d, 2 h; for 2e and
2f, 12 h), CH2Cl2 (15 mL) was added. After drying (Na2SO4), filtra-
tion and evaporation gave the residue.[In the hydrolysis of 2a, mass
spectral data were collected for these intermediates 3a and 4a: API-
MS (EI): m/z (%) = 329 (M + 1, 6), 328 (M, 26), 75 (100).
Anal. Calcd for C19H24N2O3: C, 69.49; H, 7.37; N, 8.53. Found: C,
69.85; H, 7.33; N, 8.37.
Synthesis 2000, No. 2, 265–268 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Synthesis of 1,4-Dialkyl-1,4-dihydro-1,4-benzo[e]diazepine-5-ones
MS (EI): m/z (%) = 265 (M + 1, 20), 264 (M, 100).
267
TIS m/z (%): for 3a: 207 (M + 1, 100); for 4a: 221 (M + 1, 27)]. This
residue was dissolved in toluene (15 mL) and refluxed with a
Dean-Stark trap for 2-6 h (monitored by TLC). Cooling and evap-
oration gave the residue which was purified by flash chromatogra-
phy (silica gel, hexane/Et2O, 2:1) to afford 1a-f.
Anal. Calcd for C17H16N2O: C, 77.25; H, 6.10; N, 10.60. Found: C,
77.59; H, 6.22; N, 10.52.
1e
Yield: 72%; TLC (silica gel, hexane/Et2O, 1:1); Rf 0.40.
1a
1H NMR (300 MHz, CDCl3): d = 3.83 (d, J = 5.7 Hz, 2 H), 4.80 (s,
2 H), 5.16 (dd, J = 10.3, 1.4 Hz, 1 H), 5.21 (dd, J = 17.3, 1.4 Hz, 1
H), 5.35 (d, J = 5.6 Hz, 1 H), 5.62 (d, J = 5.6 Hz, 1 H), 5.74-5.87
(m, 1 H), 6.76 (d, J = 8.2 Hz, 1 H), 6.98 (t, J = 7.3 Hz, 1 H), 7.22-
7.39 (m, 6 H), 7.80 (dd, J = 7.8, 1.6 Hz, 1 H).
13C NMR (75 MHz, CDCl3): d = 51.37, 53.15, 115.78, 117.29,
118.16, 122.08, 127.24, 127.52, 127.58, 128.44, 130.88, 131.97,
132.68, 133.79, 136.88, 154.41, 169.23.
Yield: 79%; TLC (silica gel, hexane/Et2O, 1:1); Rf 0.25.
1H NMR (400 MHz, CDCl3): d = 2.92 (s, 3 H), 3.15 (s, 3 H), 5.32
(d, J = 5.6 Hz, 1 H), 5.57 (d, J = 5.6 Hz, 1 H), 6.77 (d, J = 8.2 Hz, 1
H), 6.97 (t, J = 7.5 Hz, 1 H), 7.31 (t, J = 7.7 Hz, 1 H), 7.76 (d,
J = 7.7 Hz, 1 H).
13C NMR (100 MHz, CDCl3): d = 36.16, 38.23, 114.39, 117.52,
121.78, 127.06, 130.23, 131.99, 132.67, 154.89, 169.25.
IR (film): n = 2960, 1690, 1632, 1596, 1476, 1454, 1391, 1282,
IR (film): n = 3064, 3031, 2982, 2924, 2827, 1682, 1633 (s), 1595,
1487, 1454, 1416, 1394, 1360, 1318, 1283, 1260, 1177, 1106, 990,
925, 746, 699 cm-1.
1262, 1216, 1194, 1168, 1046, 1011, 739 cm-1.
MS (EI): m/z (%) = 189 (M + 1, 25), 188 (M, 74), 147 (100).
Anal. Calcd for C11H12N2O: C, 70.19; H, 6.43; N, 14.88. Found: C,
70.37; H, 6.49; N, 14.75.
MS (EI): m/z (%) = 291 (M + 1, 16), 290 (M, 71), 91 (100).
Anal. Calcd for C18H18N2O: C, 78.59; H, 6.25; N, 9.65. Found: C,
77.57; H, 6.22; N, 9.40.
1b
Yield: 67%; TLC (silica gel, hexane/Et2O, 1:1); Rf 0.48.
1f
1H NMR (300 MHz, CDCl3): d = 3.15 (s, 3 H), 3.87 (d, J = 5.7 Hz,
2 H), 5.24 (dd, J = 10.3, 1.4 Hz, 1 H), 5.30 (dd, J = 17.3, 1.5 Hz, 1
H), 5.36 (d, J = 5.6 Hz, 1 H), 5.62 (d, J = 5.6 Hz, 1 H), 5.83-5.96
(m, 1 H), 6.76 (d, J = 8.2 Hz, 1 H), 6.99 (td, J = 7.5, 0.8 Hz, 1 H),
7.30 (td, J = 7.5, 1.7 Hz, 1 H), 7.75 (dd, J = 7.8, 1.7Hz, 1 H).
13C NMR (75 MHz, CDCl3): d = 36.14, 53.22, 115.69, 118.18,
118.22, 121.95, 127.57, 128.80, 131.82, 132.53, 133.78, 154.18,
169.29.
Yield: 48%; mp 100-101°C (Et2O/hexane); TLC (silica gel, hex-
ane/Et2O, 1:1); Rf 0.51.
1H NMR (300 MHz, CDCl3): d = 4.41 (s, 2 H), 4.80 (s, 2 H), 5.36
(d, J = 5.6 Hz, 1 H), 5.55 (d, J = 5.6 Hz, 1 H), 6.87 (d, J = 8.2 Hz,
1 H), 7.03 (t, J = 7.5 Hz, 1 H), 7.03-7.33 (m, 11 H), 7.84 (dd,
J = 7.8, 1.6 Hz, 1 H).
13C NMR (75 MHz, CDCl3): d = 51.61, 54.51, 115.76 117.93,
122.31, 127.26, 127.75, 127.81, 128.03, 128.44, 128.46, 130.72,
132.07, 132.63, 136.96, 137.03, 154.53, 169.19 (one aromatic car-
bon signal is missing due to overlapping).
IR (film): n = 3072, 2980, 2930, 2843, 2688, 2632 (s), 1596, 1487,
1460, 1392, 1283, 1260, 1213, 1168, 1046, 992, 973, 925, 891, 827,
742 cm-1.
IR (film): n = 3059, 3030, 1632 (s), 1594, 1495, 1453, 1413, 1296,
1220, 1165, 729, 694 cm-1. MS (EI): m/z (%) = 342 (M + 2, 2), 341
(M + 1, 12), 340 (M, 45), 91 (100).
MS (EI): m/z (%) = 215 (M + 1, 15), 214 (M, 84), 132 (100).
Anal. Calcd for C13H14N2O: C, 72.87; H, 6.59; N, 13.07. Found: C,
72.95; H, 6.66; N, 12.95.
Anal. Calcd for C23H20N2O: C, 81.15; H, 5.92; N, 8.23. Found: C,
81.52; H, 6.00; N, 8.11.
1c
Yield: 83%; mp 122-123°C (Et2O/hexane); TLC (silica gel, hex-
ane/Et2O, 1:1); Rf 0.48.
Acknowledgement
1H NMR (300 MHz, CDCl3): d = 3.16 (s, 3 H), 4.45 (s, 2 H), 5.34
(d, J = 5.6 Hz, 1 H), 5.56 (d, J = 5.6 Hz, 1 H), 6.82 (d, J = 8.2 Hz,
1 H), 6.99 (t, J = 7.3 Hz, 1 H), 7.25-7.35 (m, 6 H), 7.78 (dd, J = 7.7,
1.7 Hz, 1 H).
We thank Belle Abrera and Ann Sjolander, formerly of Novartis,
for help in MS determination.
13C NMR(75 MHz, CDCl3): d = 36.11, 54.48, 115.88, 118.87,
122.19, 127.34, 127.80, 127.88, 128.52, 129.36, 131.92, 132.52,
137.05, 154.32, 169.33.
References
(1) Correspondence should be made to this author at: NitroMed
Inc., 12 Oak Park Drive, Bedford, MA 01730, USA; Fax +1
(781)2751127; E-mail: twang@nitromed.com.
MS (EI): m/z (%) = 265 (M + 1, 18), 264 (M, 37), 132 (100).
(2) Current address: Novartis Agribusiness Biotechnology and
Research Institute, 3054 Cornwallis Road, P. O. Box 12257,
Research Triangle Park, NC 27709, USA
(3) Sneader, W. In Comprehensive Medicinal Chemistry; Hansch,
C; Sammes P. G.; Taylor J. B., Eds., Pergamon: London,
1990; Vol. 1, pp 65-66.
Anal. Calcd for C17H16N2O: C, 77.25; H, 6.10; N, 10.60. Found: C,
77.30; H, 6.14; N, 10.48.
1d
Yield: 75%; TLC (silica gel, hexane/Et2O, 1:1); Rf 0.30.
1H NMR (300 MHz, CDCl3): d = 2.88 (s, 3 H), 4.79 (s, 2 H), 5.28
(d, J = 5.7 Hz, 1 H), 5.56 (d, J = 5.7 Hz, 1 H), 6.76 (d, J = 8.2 Hz,
1 H), 6.95 (t, J = 7.5 Hz, 1 H), 7.23-7.33 (m, 6 H), 7.81 (dd, J = 7.7,
1.7 Hz, 1 H).
13C NMR (75 MHz, CDCl3): d = 38.23, 51.45, 114.48, 116.06,
121.78, 126.92, 127.27, 127.57, 128.51, 131.27, 132.13, 132.86,
136.81, 154.95, 169.23.
(4) Archer, G. A.; Sternbach, L. H. Chem. Rev. 1968, 68, 747.
(5) Tucker, H.; Le Count, D. J. In Comprehensive Heterocyclic
Chemistry II; Katritzky, A. R.; Rees, C. W.; Scriven, E. F. V.,
Eds., Elsevier: Amsterdam, 1996; Vol. 9, pp 151-182.
Sharp, J. T. In Comprehensive Heterocyclic Chemistry;
Katritzky, A. P.; Rees, C. W., Eds., Pergamon: Amsterdam,
1984; Vol. 7, pp 593-620.
IR (film): n = 3062, 3030, 2962, 2879, 1689, 1633 (s), 1595, 1471,
1453, 1440, 1412, 1391, 1332, 1282, 1262, 1199, 1162, 1012, 887,
828, 736 cm-1.
(6) (a) Yoo, H. W.; Lee, J. W.; Suh, M. E. Yakhak Hoechi 1989,
33, 246; Chem Abstr. 1990, 112, 216885.
(b) We believe that the molecular ion peaks are important to
Synthesis 2000, No. 2, 265–268 ISSN 0039-7881 © Thieme Stuttgart · New York

268
T. Wang, S. Cloudsdale
PAPER
characterize the 1,4-benzodiazepin-5-ones bearing free NH
group, since those molecules tend to form dimers according to
our experience.
Article Identifier:
1437-210X,E;2000,0,02,0265,0268,ftx,en;M00999SS.pdf
(7) For a review of isatoic anhydride chemistry, see: Coppola, G.
M. Synthesis 1980, 505.
(8) Montgomery, J., Chevliakov, M. V., Brielmann, H. L.
Tetrahedron 1997, 53, 16449.
Synthesis 2000, No. 2, 265–268 ISSN 0039-7881 © Thieme Stuttgart · New York