A new synthesis of 1,2,3,5-tetrahydroimidazo[2,3-b]-[1,3]benzodiazocines

Article abstract of DOI:10.1002/jhet.5570410525

A new synthesis of 6-carbomethoxy-1,2,3,5-tetrahydroimidazo[2,3-b][1,3] benzodiazocines 13 by the intramolecular cycloaddition reaction of methyl 2-(1-aziridinylmethyl)-3-(2-ureidophenyl)propenoates 10 under Appel's dehydration conditions is described. Th

Full text of DOI:10.1002/jhet.5570410525

Sep-Oct 2004
799
A New Synthesis of 1,2,3,5-Tetrahydroimidazo[2,3-b]-
[1,3]benzodiazocines
Hyun In Cho, Seung Won Lee and Kee-Jung Lee*
Organic Synthesis Laboratory, School of Chemical Engineering,
Hanyang University, Seoul 133-791, Korea
Received May 6, 2004
A new synthesis of 6-carbomethoxy-1,2,3,5-tetrahydroimidazo[2,3-b][1,3]benzodiazocines 13 by the
intramolecular cycloaddition reaction of methyl 2-(1-aziridinylmethyl)-3-(2-ureidophenyl)propenoates 10
under Appel's dehydration conditions is described. The latter were readily obtained from 2-nitrobenzalde-
hyde with methyl acrylate through the Baylis-Hillman reaction.
J. Heterocyclic Chem., 41, 799 (2004).
The cycloaddition of three-membered ring heterocycles
zolo[4,3-a][2]benzazepines [18], and anthraquinone deriv-
atives [19]. We herein report a facile synthesis of hitherto
unknown 6-carbomethoxy-1,2,3,5-tetrahydroimidazo[2,3-
b][1,3]benzodiazocines 13 by the intramolecular cycload-
dition reaction of 2-(1-aziridinylmethyl)-3-(2-urei-
dophenyl)acrylic acid methyl esters 10 under Appel's
dehydration conditions.
with heterocumulenes is a useful method for the formation
of five-membered ring heterocycles. Aziridines and aziri-
dinium salts are known to undergo ring expansion with a
variety of unsaturated functional groups such as aldehydes
[1], ketones [2], thioketones [3], imines [4], carbon dioxide
[5,6], carbon disulfide [6], isocyanates [7], isothiocyanates
[6,7], carbodiimides [8], and sulfur diimides [9].
We recently described new routes to 1,2,4-triazole-,
pyrazole-, pyridine- and benzo-fused heterocycles such as
5,6-dihydro-7H-imidazo[1,2-b][1,2,4]triazoles 3a [10],
2,3-dihydro-1 H-imidazo[1,2-b]pyrazoles 3b [11], 2,3-
dihydro-1H-imidazo[2',3':2,3]imidazo[4,5-b]pyridines 5a
[12], and 2,3-dihydro-1H-imidazo[1, 2-a]benzimidazoles
5b [13], from N-aziridinylimino ureas 1a, N-aziridinylim-
ino carboxamides 1 b, 2-(2-methylaziridin-1-yl)-3-urei-
dopyridines 4a, and 1-(2-methylaziridin-1-yl)-2-urei-
dobenzenes 4b using Appel's dehydration conditions [14],
respectively (Scheme I).
The reaction of known methyl 3-acetoxy-2-methylene-3-
(2-nitrophenyl)propanoate (7) [20] with aziridine in the
presence of triethylamine in tetrahydrofuran at room tem-
perature for 30 minutes afforded a single product methyl 2-
(1-aziridinylmethyl)-3-(2-nitrophenyl)propenoate (8) as E-
isomer in 88% yield. The (E)-stereochemistry of 8 was
1
determined by the H NMR spectral analysis of methine
proton in comparison with literature values [21].
Nitrophenylpropenoate 8 on hydrogenation over 5% Pd/C in
ethanol gave 63% yield of methyl 3-(2-aminophenyl)-2-(1-
aziridinylmethyl)propenoate (9). Compound 9 was reacted
with an equivalent of isocyanates in dichloromethane at
room temperature to give methyl 2-(1-aziridinylmethyl)-3-
(2-ureidophenyl)propenoates 1 0 in 84-95% yields.
Reaction of ureas 10 with triphenylphosphine, carbon
tetrachloride, and triethylamine in refluxing dichloro-
methane for 5 hours afforded 6-carbomethoxy-1,2,3,5-
tetrahydroimidazo[2,3-b][1,3]benzodiazocines 13 in 50-
66% yields, and which constitute unexplored class of com-
pounds. A suitable mechanism for the formation of 13 is
depicted in Scheme II. Although the isolation of carbodi-
imide 11 was unsuccessful under the reaction conditions, a
nucleophilic attack of aziridine to carbodiimide gave the
zwitterionic aziridinium ion 12 followed by aziridine ring
opening by the attack of nitrogen anion to give 13, or a
direct intramolecular cycloaddition reaction of aziridine
with carbodiimide in a concerted manner produced 13.
The structure of 13 was established on the basis of spec-
troscopic data. In the 1H NMR spectra, the chemical shift
of the methine proton of C7 was found at δ = 7.96-8.06 as
a singlet and six methylene protons of C2, C3 and C5 were
observed at δ = 3.42-3.97 as a broad singlet, δ = 3.21-3.68
as a multiplet and δ = 3.89-4.21 as a broad singlet, and
proved to be correlated to the C5 (δ = 44.9), C2 (δ = 45.7),
C3 (δ = 47.2) and C7 (δ = 146.7) carbon atoms by two
dimensional carbon-proton heteronuclear correlation spec-
In addition, the Baylis-Hillman reaction has been the
subject of recent reviews [15] and continues to elicit atten-
tion. We have demonstrated applications of this reaction in
the syntheses of 3-oxo-2,3-dihydro-1H-isoindoles [16],
4H-tetrazolo[1,5-a][1]benzazepines [17], 5H- 1 , 2 , 3 - t r i a-

800
H. I. Cho, S. W. Lee and K.-J. Lee
Vol. 41
cium hydride. Silica gel 60 (70-230 mesh ASTM) used for column
chromatography was supplied by E. Merck. Analytical thin layer
chromatography (tlc) was carried out on Merck silica gel 60 F tlc
254
plates. Melting points were taken using an Electrothermal melting
point apparatus and are uncorrected. Microanalyses were obtained
using a Carlo Erba EA 1180 element analyzer. Mass spectra were
obtained using a ThermoQuest Polaris Q mass spectrometer operat-
ing at 70 eV. Infrared spectra were recorded on a Nicolet Magna
1
13
550 FTIR spectrometer. The H and C NMR spectra were mea-
sured on a Gemini 300 spectrometer. The HMBC and DEPT spec-
tra were obtained on a 300 MHz Bruker spectrometer. All chemical
shifts are reported in parts per million (δ) relative to tetramethylsi-
lane and coupling constants (J) are expressed in Hertz.
Methyl 2-(1-Aziridinylmethyl)-3-(2-nitrophenyl)propenoate (8).
To a solution of methyl 3-acetoxy-2-methylene-3-(2-nitro-
phenyl)propanoate 7 (4.00 g, 14 mmoles) in tetrahydrofuran (20
ml) was added triethylamine (5.78 g, 57 mmoles) and aziridine
(2.16 g, 50 mmoles), and the mixture was stirred for 30 minutes
at room temperature. The solvent was removed in vacuo and the
residue was partioned between water (10 ml) and
dichloromethane (20 ml x 2). The dichloromethane layer was
removed after drying over anhydrous magnesium sulfate to give
3.32 g (88%) of 8 as a pale yellow solid after crystallization with
ethyl acetate-petroleum ether; mp 96-98 °C; ir (potassium bro-
–1
1
mide): 1714, 1636, 1606, 1570, 1513, 1427, 1338 cm ; H nmr
(deuteriochloroform): δ 1.29 (m, 2H, CH ), 1.72 (m, 2H, CH ),
3.05 (s, 2H, CH ), 3.88 (s, 3H, OCH ), 7.56 (dd, 1H, J = 8.2 and
2
2
2
3
7.6 Hz, aromatic), 7.71 (dd, 1H, J = 7.6 and 7.6 Hz, aromatic),
7.87 (d, 1H, J = 7.6 Hz, aromatic), 8.07 (s, 1H, CH), 8.16 (d, 1H,
13
J = 8.2 Hz, aromatic); C nmr (deuteriochloroform): δ 27.6,
52.3, 56.2, 124.7, 129.4, 131.0, 131.4, 132.0, 133.4, 138.5, 147.6,
+
167.6; ms m/z (%) 262 (M , 100), 183 (94), 152 (20), 108 (27).
A n a l. Calcd. for C H N O : C, 59.54; H, 5.38; N, 10.68.
13 14
Found: C, 59.21; H, 5.23; N, 10.47.
2 4
Methyl 3-(2-Aminophenyl)-2-(1-aziridinylmethyl)propenoate
(9).
troscopy (HETCOR) and the DEPT 13C NMR spectrum of
13c. Also in the HMBC spectrum of 13c C7 methine pro-
ton (δ = 8.06) was correlated with C5 carbon (δ = 44.9)
and aromatic carbons. The IR spectra showed absorption
band in 1712-1719 cm–1 assignable for the ester carbonyl
bond. The mass spectral data showed all M+ peaks and
characteristic decomposition peak at m/z = (M+ -CO2Me)
as a base peak except for 13f.
In conclusion, a new synthesis of tetrahydroimi-
dazo[2,3-b][1,3]benzodiazocines 13 by the intramolecular
cycloaddition rection of 2-(1-aziridinylmethyl)-3-(2-urei-
dophenyl)acrylic acid methyl esters 10, readily obtainable
through the Baylis-Hillman adducts, under Appel's condi-
tions was achieved.
To a solution of the nitro compound 8 (2.62 g, 10 mmoles) in
ethanol (50 ml) was added 5% Pd/C (1.31 g, 0.6 mmoles) and the
mixture was stirred under hydrogen at atmospheric pressure and
room temperature for 2 hours. The reaction mixture was filtered
through celite and the filtrate was evaporated in vacuo to give an
oily residue. The residue was chromatographed on silica gel col-
umn and eluted with hexane-ethyl acetate-methanol (V/V =
20:20:1) to give 1.46 g (63%) of 9 as a pale yellow solid after
crystallization with petroleum ether; mp 136-138 °C; ir (potas-
–1
1
sium bromide): 3330, 3206, 1688, 1657, 1618, 1485 cm ; H
nmr (deuteriochloroform): δ 1.30 (m, 2H, CH ), 1.73 (m, 2H,
2
CH ), 3.16 (s, 2H, CH ), 3.86 (s, 3H, OCH ), 3.92 (br s, 2H,
2
NH , exchangeable in deuterium oxide), 6.72 (d, 1H, J = 8.2 Hz,
2
3
2
aromatic), 6.79 (dd, 1H, J = 7.6 and 7.6 Hz, aromatic), 7.16 (dd,
1H J = 7.9 and 7.6 Hz, aromatic), 7.36 (d, 1H, J = 7.6 Hz, aro-
13
matic), 7.75 (s, 1H, CH); C nmr (deuteriochloroform): δ 27.7,
52.0, 56.4, 115.6, 118.1, 120.5, 130.1 (two), 131.6, 138.5, 144.7,
+
163.5; ms m/z (%) 232 (M , 4), 201 (57), 188 (75), 158 (49), 130
EXPERIMENTAL
(100), 103(17).
A n a l. Calcd. for C H N O : C, 67.22; H, 6.94; N, 12.06.
Aziridine [22] and methyl 3-acetoxy-2-methylene-3-(2-nitro-
phenyl)propanoate (7) [20] were prepared following literature pro-
cedures. Isocyanates were purchased from Aldrich and used with-
out further purification. Tetrahydrofuran was distilled from sodium
benzophenone ketyl and dichloromethane was distilled from cal-
13 16 2 2
Found: C, 67.48; H, 6.71; N, 12.38.
Methyl 2-(1-Aziridinylmethyl)-3-[2-(3-phenylureido)phenyl]-
propenoate (10a).

Sep-Oct 2004
A New Synthesis of 1,2,3,5-Tetrahydroimidazo[2,3-b][1,3]benzodiazocines
801
To a stirred solution of the amino compound 9 (1.16 g, 5
mmoles) in dichloromethane (10 ml) was added phenyl isocyanate
(0.60 g, 5 mmoles) at room temperature. After 5 minutes the sol-
vent was removed in vacuo. The residue was crystallized with
ether to give 1.49 g (85%) of 10a as a white solid; mp 132-133 °C;
Treatment of 9 (1.16 g, 5 mmoles) with methyl isocyanate
(0.29 g, 5 mmoles) following the similar procedure described for
10a at room temperature for 4 hours afforded 1.32 g (91%) of 10e
as a white solid; mp 114 °C; ir (potassium bromide): 3414, 1698,
–1
1
1656 cm ; H nmr (deuteriochloroform): δ 1.47 (m, 2H, CH ),
2
1.77 (m, 2H, CH ), 2.73 (d, 3H, J = 4.5 Hz, NCH ), 3.06 (s, 2H,
–1 1
ir (potassium bromide): 3326, 1712, 1650 cm ; H nmr (dimethyl
sulfoxide-d ): δ 1.30 (m, 2H, CH ), 1.64 (m, 2H, CH ), 3.10 (s,
2
CH ), 3.85 (s, 3H, OCH ), 4.96 (br s, 1H, NH), 7.03-7.35 (m, 3H,
3
6
2H, CH ), 3.83 (s, 3H, CH ), 6.95-7.46 (m, 9H, aromatic), 7.74 (s,
2
2
2
3
aromatic), 7.76 (s, 1H, CH), 7.94-7.96 (m, 1H, aromatic), 8.28
2
1H, CH), 8.19 (s, 1H, NH), 9.04 (s, 1H, NH); C nmr (dimethyl
3
13
13
(br s, 1H, NH); C nmr (deuteriochloroform): δ 26.7, 27.8, 52.2,
sulfoxide-d ): δ 27.3, 52.6, 56.5, 118.7, 119.8, 122.4, 123.0, 126.4,
56.0, 122.8, 126.1, 129.3, 129.4, 132.0, 137.1, 140.1, 140.2,
156.6, 167.8.
A n a l. Calcd. for C H N O : C, 62.27; H, 6.62; N, 14.52.
6
129.3, 129.7, 132.2, 137.2, 138.1, 140.1, 141.8, 153.0, 168.4.
A n a l. Calcd. for C H N O : C, 68.36; H, 6.02; N, 11.96.
20 21
Found: C, 68.12; H, 5.85; N, 11.73.
3 3
15 19
3 3
Found: C, 62.53; H, 6.85; N, 14.30.
Methyl 2-(1-Aziridinylmethyl)-3-[2-(3-p-chlorophenylureido)-
phenyl]propenoate (10b).
Methyl 2-(1-Aziridinylmethyl)-3-[2-(3-benzoylureido)phenyl]-
propenoate (10f).
Treatment of 9 (1.16 g, 5 mmoles) with 4-chlorophenyl iso-
cyanate (0.77 g, 5 mmoles) following the same procedure
described for 10a afforded 1.68 g (87%) of 10b as a white solid;
Treatment of 9 (1.16 g, 5 mmoles) with benzoyl isocyanate
(0.74 g, 5 mmoles) following the same procedure described for
10a afforded 1.59 g (84%) of 10b as a white solid; mp 158-160
–1
–1
1
mp 154-156 °C; ir (potassium bromide): 3271, 1708, 1632 cm ;
1
°C; ir (potassium bromide): 3256, 1727, 1704, 1672 cm ; H
nmr (dimethyl sulfoxide-d ): δ 1.22 (m, 2H, CH ), 1.57 (m, 2H,
H nmr (dimethyl sulfoxide-d ): δ 1.26 (m, 2H, CH ), 1.59 (m,
6
2H, CH ), 3.05 (s, 2H, CH ), 3.79 (s, 3H, CH ), 7.11-7.49 (m,
2
6
CH ), 3.02 (s, 3H, CH ), 3.80 (s, 3H, CH ), 7.21-7.75 (m, 6H,
2
2
2
6H, aromatic), 7.71 (s, 1H, CH), 7.74-7.88 (m, 2H, aromatic),
3
2
aromatic), 7.79 (m, 1H, CH), 7.85-8.06 (m, 3H, aromatic);
2
3
13
C
nmr (dimethyl sulfoxide-d ): δ 26.8, 52.3, 56.0, 120.7, 126.6,
13
8.20 (s, 1H, NH), 9.13 (s, 1H, NH); C nmr (dimethyl sulfoxide-
d ): δ 27.3, 52.6, 56.5, 120.2, 122.5, 123.4, 126.0, 126.6, 129.2,
6
127.6, 128.1, 128.3, 128.6, 128.9, 132.2, 133.0, 135.3, 135.9,
139.6, 151.3, 169.0, 170.9.
Anal. Calcd. for C H N O : C, 66.48; H, 5.58; N, 11.08.
6
130.5, 132.3, 137.9, 138.3, 138.4, 139.1, 152.8, 168.3.
Anal. Calcd. for C H ClN O : C, 62.26; H, 5.22; N, 10.89.
20 20
3 3
Found: C, 62.49; H, 5.01; N, 10.58.
21 21
3 4
Found: C, 66.23; H, 5.39; N, 10.78.
Methyl 2-(1-Aziridinylmethyl)-3-[2-(3-p-fluorophenylureido)-
phenyl]propenoate (10c).
6-Carbomethoxy-1-phenyl-1, 2, 3, 5-tetrahydroimidazo[2, 3- b]-
[1,3]benzodiazocine (13a).
Treatment of 9 (1.16 g, 5 mmoles) with 4-fluorophenyl iso-
cyanate (0.69 g, 5 mmoles) following the same procedure
described for 10a afforded 1.75 g (95%) of 10c as a white solide;
To a stirred solution of urea 10a (1.05 g, 3 mmoles) in
dichloromethane (30 ml) was added triphenylphosphine (1.96 g,
7.5 mmoles), carbon tetrachloride (1.5 ml, 15 mmoles), and tri-
ethylamine (1.05 ml, 7.5 mmoles). The mixture was heated to
reflux temperature for 5 hours. After cooling to room tempera-
ture, the reaction mixture was partitioned between water (10 ml)
and dichloromethane (20 ml x 2). After drying over anhydrous
magnesium sulfate the solvent was removed and the residue was
chromatographed on silica gel column, eluted with hexane-ethyl
acetate (V/V = 2:1) to give 0.63 g (63%) of 13a as a pale yellow
solid after crystallization with diethyl ether-hexane; mp 137-138
–1
mp 129-130 °C; ir (potassium bromide): 3311, 1713, 1650 cm ;
1
H nmr (dimethyl sulfoxide-d ): δ 1.26 (m, 2H, CH ), 1.59 (m,
6
2H, CH ), 3.05 (s, 2H, CH ), 3.79 (s, 3H, CH ), 7.07-7.39 (m,
2
2
6H, aromatic), 7.71 (s, 1H, CH), 7.73-7.91 (m, 2H, aromatic),
2
3
13
8.12 (s, 1H, NH), 8.91 (s, 1H, NH); C nmr (dimethyl sulfoxide-
d ): δ 26.8, 52.3, 56.5, 115.0 (d, J = 22 Hz), 115.9, 119.5,
6
120.3, 125.3, 126.0 129.8, 131.8, 132.6, 135.9, 137.6, 152.5,
CF
157.4 (d, J = 239 Hz), 168.1.
CF
Anal. Calcd. for C H FN O : C, 65.03; H, 5.46; N, 11.38.
–1
1
20 20 3 3
Found: C, 64.75; H, 5.19; N, 11.17.
°C; ir (potassium bromide): 1713, 1658 cm ; H nmr (deuteri-
ochloroform): δ 3.59 (br s, 2H, CH ), 3.75 (m, 2H, CH ), 3.85 (s,
3H, CH ), 4.10 (br s, 2H, CH ), 6.91-7.03 (m, 4H, aromatic),
2
2
Methyl 2-(1-Aziridinylmethyl)-3-[2-(3-p-methylphenylureido)-
phenyl]propenoate (10d).
3
2
7.25-7.32 (m, 3H, aromatic), 7.62-7.64 (m, 2H, aromatic), 8.06
13
(s, 1H, CH); C nmr (deuteriochloroform): δ 44.9, 45.2, 47.2,
52.2, 119.6, 120.5, 122.2, 125.5, 127.5, 128.4, 128.7, 129.7,
Treatment of 9 (1.16 g, 5 mmoles) with 4-methylphenyl iso-
cyanate (0.67 g, 5 mmoles) following the same procedure described
for 10a afforded 1.61 g (88%) of 10d as a white solid; mp 128-130
+
130.5, 141.5, 146.7, 148.1, 149.6, 168.2; ms: m/z (%) 333 (M ,
10), 274 (100), 130 (5).
A n a l. Calcd. for C H N O : C, 72.05; H, 5.74; N, 12.60.
–1
1
°C; ir (potassium bromide): 3292, 1708, 1633 cm ; H nmr
(dimethyl sulfoxide-d ): δ 1.26 (m, 2H, CH ), 1.59 (m, 2H, CH ),
2.24 (s, 3H, CH ), 3.05 (s, 2H, CH ), 3.79 (s, 3H, OCH ), 7.07-7.39
20 19 3 2
Found: C, 71.84; H, 5.49; N, 12.38.
6
2
2
3
2
3
(m, 6H, aromatic), 7.70 (s, 1H, CH), 7.73-7.91 (m, 2H, aromatic),
6-Carbomethoxy-1-(p-chlorophenyl)-1, 2, 3, 5-tetrahydroimi -
dazo[2,3-b][1,3]benzodiazocine (13b).
13
8.12 (s, 1H, NH), 8.91 (s, 1H, NH); C nmr (dimethyl sulfoxide-
d ): δ 20.9, 27.4, 52.6, 56.5, 118.8, 123.1, 126.2, 129.8, 130.0,
6
130.5, 131.0, 131.3, 132.3, 137.5, 137.7, 138.2, 152.9, 168.4.
A n a l. Calcd. for C H N O : C, 69.02; H, 6.34; N, 11.50.
Treatment of urea 10b (1.16 g, 3 mmoles) with Appel's
reagents following the same procedure described for 13a p r o-
vided 0.73 g (66%) of 13b as a pale yellow solid; mp 175-176 °C;
21 23
Found: C, 68.78; H, 6.10; N, 11.21.
3 3
–1 1
ir (potassium bromide ): 1713, 1656 cm ; H nmr (deuteriochlo-
roform): δ 3.59 (br s, 2H, CH ), 3.70 (m, 2H, CH ), 3.85 (s, 3H,
Methyl 2-(1-Aziridinylmethyl)-3-[2-(3-methylureido)phenyl]-
propenoate (10e).
2
CH ), 4.21 (br s, 2H, CH ), 6.90-7.02 (m, 3H, aromatic), 7.21-
2
3
2

802
H. I. Cho, S. W. Lee and K.-J. Lee
Vol. 41
7.30 (m, 3H, aromatic), 7.56-7.63 (m, 2H, aromatic), 8.06 (s, 1H,
13
CH); C nmr (deuteriochloroform): δ 44.8, 45.1, 47.0, 52.3,
reagents following the same procedure described for 13a p r o-
vided 0.60 g (55%) of 13f as a pale yellow solid; mp 146-148 °C;
–1 1
ir (potassium bromide): 1702, 1698, 1650 cm ; H nmr (deuteri-
120.3, 125.5, 127.0, 127.4, 128.1, 128.3, 128.8, 129.7, 130.6,
+
140.1, 146.6, 147.7, 149.4, 168.1; ms: m/z (%) 369 (3), 367 (M
, 8), 310 (34), 308 (100), 130 (9).
Anal. Calcd. for C H ClN O : C, 65.31; H, 4.93; N, 11.42.
ochloroform): δ 3.68 (br s, 2H, CH ), 3.88 (s, 3H, CH ), 3.97 (m,
2 3
2H, CH ), 4.19 (br s, 2H, CH ), 6.34-6.37 (m, 1H, aromatic),
2 2
6.83-6.91 (m, 2H, aromatic), 7.08-7.12 (m, 1H, aromatic), 7.31-
20 18
Found: C, 65.59; H, 5.31; N, 11.20.
3 2
7,38 (m, 3H, aromatic), 7.55-7.58 (m, 2H, CH ), 7.96 (s, 1H,
13
2
CH); C nmr (deuteriochloroform): δ 43.2, 44.2, 46.4, 52.3,
121.4, 124.7, 126.7, 127.2, 128.4, 128.7, 129.7, 130.2, 130.4,
6-Carbomethoxy-1-(p-fluorophenyl)-1,2,3,5-tetrahydroimidazo-
[2,3-b][1,3]benzodiazocine (13c).
+
136.3, 145.5, 145.9, 146.2, 167.8, 170.5; ms: m/z (%) 361 (M ,
Treatment of urea 10c (1.10 g, 3 mmoles) with Appel's
reagents following the same procedure described for 13a p r o-
vided 0.53 g (50%) of 13c as a pale yellow solid; mp 113-114 °C;
17), 302 (95), 105 (100), 77 (33).
Anal. Calcd. for C H N O : C, 69.79; H, 5.30; N, 11.63.
21 19 3 3
Found: C, 69.47; H, 5.12; N, 11.40.
–1 1
ir (potassium bromide): 1715, 1657 cm ; H nmr (deuteriochlo-
roform): δ 3.59 (br s, 2H, CH ), 3.71 (m, 2H, CH ), 3.86 (s, 3H,
2
CH ), 4.18 (br s, 2H, CH ), 6.89-7.01 (m, 5H, aromatic), 7.24-
2
REFERENCES AND NOTES
3
2
7.29 (m, 1H, aromatic), 7.55-7.59 (m, 2H, aromatic), 8.06 (s, 1H,
*
Author to whom correspondence should be addressed.
[1] N. J. Leonard, E. F. Kiefer and L. E. Brady, J. Org. Chem., 28,
2850 (1963).
[2] N. J. Leonard, J. V. Paukstelis and L. E. Brady, J. Org. Chem.,
29, 3383 (1964).
[3] R. A. Wohl and D. F. Headley, J. Org. Chem., 37, 4401
(1972).
13
CH); C nmr (deuteriochloroform): δ 44.8, 45.6, 47.2, 52.2,
114.9 (d, J = 22 Hz), 120.6, 121.3, 125.5, 127.5, 128.7, 129.7,
CF
130.5, 137.7, 146.6, 147.9, 149.8, 158.3 (d, J = 242 Hz), 168.2;
CF
ms: m/z (%) 351 (M , 10), 292 (100), 130 (9).
Anal. Calcd. for C H FN O : C, 68.36; H, 5.16; N, 11.96.
+
20 18
3 2
Found: C, 68.18; H, 4.89; N, 12.23.
[4] O. C. Dermer and G. E. Ham, In Ethylenimine and Other
Aziridines, Academic Press, New York and Londone, 1969, Chapter 3.
[5] A. Hassner and S. S. Burke, Tetrahedron, 30, 2613 (1974).
[6a] R. Nomura, T. Nakano, Y. Nishio, A. Ogawa, A. Ninagawa
and H. Matsuda, Chem. Ber., 122, 2407 (1989); [b] H. Matsuda, A.
Ninagawa and H. Hasegawa, Bull. Chem. Soc. Jpn., 58, 2717 (1985).
[7] E. Pfeil and K. Milzner, Angew. Chem. Int. Ed., 5, 667 (1966).
[8] J. -O. Baeg and H. Alper, J. Org. Chem., 57, 157 (1992).
[9] J. -O. Baeg and H. Alper, J. Am. Chem. S o c., 116, 1220
(1994).
[10] K. -J. Lee and S. -U. Kang, Te t r a h e d ron Lett., 36, 2815
(1995).
[11] K. -J. Lee, D. -W. Kim and B. -G. Kim, J. Heterocyclic Chem.,
40, 363 (2003).
[12] J. -S. Lim and K. -J. Lee, J. Heterocyclic Chem., 3 9, 975
(2002).
[13] H. I. Cho and K. -J. Lee, Bull. Korean Chem. Soc., 24, 189
(2003).
6 - C a r b o m e t h o x y - 1 - (p- m e t h y l p h e n y l ) - 1 , 2 , 3 , 5 - t e t r a h y d r o -
imidazo[2,3-b][1,3]benzodiazocine (13d).
Treatment of urea 10d (1.09 g, 3 mmoles) with Appel's
reagents following the same procedure described for 13a p r o-
vided 0.57 g (55%) of 13d as a pale yellow solid; mp 153-155 °C;
–1 1
ir (potassium bromide): 1712, 1651 cm ; H nmr (deuteriochlo-
roform): δ 2.29 (s, 3H, CH3), 3.58 (br s, 2H, CH ), 3.71 (m, 2H,
2
CH ), 3.86 (s, 3H, OCH ), 4.12 (br s, 2H, CH2), 6.87-7.01 (m,
2
3
3H, aromatic), 7.09 (d, 2H, J = 8.4 Hz, aromatic), 7.22-7.28 (m,
1H, aromatic), 7.46 (d, 2H, J = 8.4 Hz, aromatic), 8.06 (s, 1H,
13
CH); C nmr (deuteriochloroform): δ 20.7, 44.8, 45.4, 47.3,
52.2, 119.8, 120.3, 125.5, 127.4, 128.7, 128.9, 129.7, 130.4,
+
131.8, 139.1, 146.7, 148.2, 149.8, 168.2; ms: m/z (%) 347 (M ,
8), 288 (100), 130 (13).
Anal. Calcd. for C H N O : C, 72.60; H, 6.09; N, 12.10.
21 21 3 2
Found: C, 72.43; H, 5.82; N, 11.78.
[14] R. Appel, R. Kleinstück and K. -D. Ziehn, Chem. Ber., 104,
1335 (1971).
6-Carbomethoxy-1-methyl-1, 2, 3, 5-tetrahydroimidazo[2, 3-b]-
[1,3]benzodiazocine (13e).
[15] For review of the Baylis-Hillman reaction, see; [a] S. E.
Drewes and G. H. P. Roos, Tetrahedron 44 , 4653 (1988); [b] D.
Basavaiah, P. D. Rao and R. S. Hyma, Tetrahedron 52, 8001 (1996); [c]
E. Ciganek, In Organic Reactions; Paquette, L. A., Ed., Wiley, New York,
1997, Vol. 51, p 201; [d] P. Langer, Angew. Chem. Int. Ed., 39 , 3049
(2000); [e] J. N. Kim and K. Y. Lee, Curr. Org. Chem. 6, 627, (2002); [f]
D. Basavaiah, A. J. Rao and T. Satyanarayana, Chem. Rev., 1 0 3, 811,
(2003).
[16] Y. S. Song, C. H. Lee and K. -J. Lee, J. Heterocyclic Chem.,
40, 939 (2003).
[17] C. H. Lee, Y. S. Song, H. I. Cho, J. W. Yang and K. -J. Lee, J.
Heterocyclic Chem., 40, 1103 (2003).
Treatment of urea 10e (0.87 g, 3 mmoles) with Appel's
reagents following the same procedure described for 13a p r o-
vided 0.51 g (62%) of 13e as a pale yellow solid; mp 79-80 °C; ir
–1 1
(potassium bromide): 1719, 1657 cm ; H nmr (deuteriochloro-
form): δ 2.81 (s, 3H, NCH ), 3.21 (br s, 2H, CH ), 3.42 (m, 2H,
3
CH ), 3.83 (s, 3H, OCH ), 3.89 (br s, 2H, CH ), 6.86-6.98 (m,
2
2
3H, aromatic), 7.22-7.28 (m, 1H, aromatic), 8.03 (s, 1H, CH);
3
2
13
C nmr (deuteriochloroform): δ 33.6, 44.5, 47.5, 47.7, 52.1,
120.4, 126.0, 127.9, 128.6, 130.1, 130.3, 146.6, 148.9, 154.3,
+
168.1; ms: m/z (%) 271 (M , 9), 212 (100).
A n a l. Calcd. for C H N O : C, 66.40; H, 6.32; N, 15.49.
[18] S. H. Ko and K. -J. Lee, J. Heterocyclic Chem., 41 (2004) in
press.
15 17
Found: C, 66.21; H, 6.07; N, 15.78.
3 2
[19] C. H. Lee and K. -J. Lee, Synthesis, (2004) accepted.
[20] P. H. Mason and N. D. Emslie, Tetrahedron, 50, 12001 (1994).
[21] D. Nilov, R. Räcker and O. Reiser, Synthesis, 2232 (2002).
[22] V. P. Wystrach, D. W. Kaiser and F. C. Schaefer, J. Am. Chem.
Soc., 77, 5915 (1955).
1-Benzoyl-6-carbomethoxy-1,2,3,5-tetrahydroimidazo[2,3-b]-
[1,3]benzodiazocine (13f).
Treatment of urea 10f (1.14 g, 3 mmoles) with Appel's