Morita-Baylis-Hillman route to 4H-pyrrolo[1,2-a][1]benzazepine derivatives

Article abstract of DOI:10.1016/j.tet.2009.04.026

A simple method for synthesizing substituted 4H-pyrrolo[1,2-a][1]benzazepines using acid-assisted cyclization of the Morita-Baylis-Hillman adducts of 2-(1H-pyrrol-1-yl)benzaldehydes with methyl acrylate or methyl vinyl ketone as a key step has been developed.

Full text of DOI:10.1016/j.tet.2009.04.026

Tetrahedron 65 (2009) 4703–4708
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Tetrahedron
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Morita–Baylis–Hillman route to 4H-pyrrolo[1,2-a][1]benzazepine derivatives
*
Sun Pil Park, Young Seok Song, Kee-Jung Lee
Organic Synthesis Laboratory, Department of Chemical Engineering, Hanyang University, Seoul 133-791, Republic of Korea
a r t i c l e i n f o
a b s t r a c t
Article history:
A simple method for synthesizing substituted 4H-pyrrolo[1,2-a][1]benzazepines using acid-assisted cy-
clization of the Morita–Baylis–Hillman adducts of 2-(1H-pyrrol-1-yl)benzaldehydes with methyl acrylate
or methyl vinyl ketone as a key step has been developed.
Received 19 February 2009
Received in revised form 8 April 2009
Accepted 8 April 2009
Ó 2009 Elsevier Ltd. All rights reserved.
Available online 16 April 2009
Keywords:
Morita–Baylis–Hillman
4H-Pyrrolo[1,2-a][1]benzazepines
2-(1H-Pyrrol-1-yl)benzaldehydes
Friedel–Crafts reaction
Sulfuric acid
1. Introduction
dehyde by Friedel–Crafts reaction with sulfuric acid, respectively, as
shown in Scheme 1.
Pyrrolo[1,2-a][1]benzazepine derivatives have attracted the
attention of synthetic chemists due to their potential biological
activity.1 There are only a few known synthetic approaches to pyr-
rolo[1,2-a][1]benzazepine ring systems. The Wadsworth–Emmons
olefination between 2-(1H-pyrrol-1-yl)benzaldehyde and methyl
a
-(diethylphosphonyl)phenylacetate led to the methyl 2-(1H-pyr-
rol-1-yl)- -phenylcinnamate, which, after transformation into the
a
corresponding acid chloride, was cyclized to the 5-phenyl-4H-pyr-
rolo[1,2-a][1]benzazepine-4-one.2 The 1-benzazepine-2-one was
N-alkylated with ethyl 2-bromopropionate, the ethyl ester was
Scheme 1.
Herein, we describe the synthesis of 4H-pyrrolo[1,2-a][1]ben-
zazepine derivatives from the Morita–Baylis–Hillman adducts of 2-
(1H-pyrrol-1-yl)benzaldehydes with methyl acrylate and methyl
vinyl ketone.
hydrolyzed, and the resulting
a-amino acids were treated with
acetic anhydride to the mesoionic oxazolone, which underwent 1,3-
dipolar cycloaddition with dimethyl acetylenedicarboxylate to give
dimethyl 1-methyl-5,6-dihydro-4H-pyrrolo[1,2-a][1]benzazepine-
2,3-dicaboxylate.1b Transition metal catalyzed cycloisomerization
reaction of 2-allenyl-1-(1H-pyrrol-1-yl)benzene produced pyrrolo-
benzazepine.3 In our program aimed at expanding the repertoire of
synthetic applications of the Morita–Baylis–Hillman chemistry4 for
the preparation of heterocyclic systems we have reported the
synthesis of 2-(9-fluorenyl)acrylic acid methyl esters,5 4H-indeno[1,2-
b]thiophenes, 8H-indeno[2,1-b]thiophenes, and 8H-indeno[2,1-
b]furans having acrylic acid unit,6 from the Morita–Baylis–Hillman
adducts of 2-biphenylcarboxaldehyde, 2-(thiophen-2-yl)benzalde-
hyde, 2-(thiophen-3-yl)benzaldehyde, and 2-(furan-3-yl)benzal-
2. Results and discussion
Our synthesis commenced by generation of key starting material
2-(1H-pyrrol-1-yl)benzaldehydes 4a–e from methyl anthranilates
1a–e following the earlier reported procedure7 (Scheme 2). The
condensation of 2,5-dimethoxytetrahydrofuran with methyl an-
thranilate1a–eproceeded ingood yields andaffordedmethyl-2-(1H-
pyrrol-1-yl)phenylbenzoates 2a–e.8 Reduction of 2a–e with lithium
aluminium hydride in tetrahydrofuran and acidification provided
the 2-(1H-pyrrol-1-yl)phenylmethanols 3a–e. Oxidation of the
latter with pyridinium chlorochromate (PCC) in dichloromethane
gave 2-(1H-pyrrol-1-yl)benzaldehydes 4a–e. The nitro-substituted
benzaldehyde 4f was synthesized through palladium-catalyzed
* Corresponding author. Tel.: þ822 2220 0528; fax: þ822 2298 4101.
E-mail address: leekj@hanyang.ac.kr (K.-J. Lee).
0040-4020/$ – see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2009.04.026

4704
S.P. Park et al. / Tetrahedron 65 (2009) 4703–4708
Scheme 2. Reagents and conditions: (i) 2,5-dimethoxytetrahydrofuran, AcOH, reflux, 1–4 h; (ii) LAH, THF, rt, 30–60 min; (iii) PCC, Celite, CH2Cl2, rt 40–60 min; (iv) method A:
methyl acrylate, DABCO, N(CH2CH2OH)3, rt, 7 h to 3 days. method B: methyl vinyl ketone, DMAP, DMF, rt, 1–20 days; (v) 95% H2SO4, CCL4, rt, 10 min; (vi) pyrrole, xanthos, Pd(OAc)2,
K2CO3, o-xylene, 120 ꢀC, 13 h.
amination of 2-chloro-5-nitrobenzldehyde (7) with pyrrole in the
presence of xantphos following recently published procedure.9
The Morita–Baylis–Hillman reaction of 4a–f with methyl acry-
late, 1,4-diazabicyclo[2,2,2]octane (DABCO), and triethanolamine
without solvent the Morita–Baylis–Hillman adducts 5a–f were
produced in 75–98% yields. On Friedel–Crafts cyclization of 5a–f
with 95% sulfuric acid in tetrachloromethane at room temperature
for 10 min, methyl 4H-pyrrolo[1,2-a][1]benzazepine-5-carboxyl-
ates 6a–f were obtained in 70–96% yields (Scheme 2, Table 1). The
possible five-membered ring closure product 9H-pyrrolo[1,2-a]in-
dole derivatives were not produced at all. Bro¨nsted-acid-catalyzed
allylation of electron-rich arenes including 2-methylfuran and
pyrrole with substituted allylic and secondary benzylic alcohols
gives the corresponding branched allylated products with a high
regioselectivity.10 The different ring closure mode between pyrrole-
and furan/thiophene-substituted Morita–Baylis–Hillman adducts
is uncertain. With the intent to introduce more diversity in the
products employing this strategy, it was decided to carry the
Morita–Baylis–Hillman reaction of 4a–f with methyl vinyl ketone.
Consequently, the reaction of 4a–f with methyl vinyl ketone,
N,N-dimethylaminopyridine (DMAP) in N,N-dimethylformamide
yielded the adducts 5g–l, which were unstable and could not be
isolated as a pure form. As a result the crude Morita–Baylis–
Hillman adducts 5g–l were subjected to treatment with 95%
sulfuric acid similarly led to the formation of the corresponding
benzazepines 6g–l in 33–57% two-step yields. It works well with
hydrogen, electron-withdrawing or electron-donating substituents
on the phenyl ring of the Morita–Baylis–Hillman adducts.
3. Conclusions
In summary, we have achieved for the expedient synthesis of
4H-pyrrolo[1,2-a][1]benzazepine derivatives from the Morita–
Baylis–Hillman adducts of 2-(1H-pyrrol-1-yl)benzaldehydes under
the acidic condition. This method may be of value in organic syn-
thesis because of the ease of operation.
Table 1
Preparation of Morita–Baylis–Hillman adducts
azepines 6
5 and 4H-pyrrolo[1,2-a][1]benz-
4. Experimental
Entry
4
Methoda
5 (Yield %)b
6 (Yield %)c
4.1. Synthesis general
1
2
3
4
5
6
7
8
4a
4b
4c
4d
4e
4f
4a
4b
4c
4d
4e
4f
A
A
A
A
A
A
B
B
B
B
B
B
5a (82)
5b (82)
5c (88)
5d (90)
5e (75)
5f (98)
5g
5h
5i
5j
5k
6a (79)
6b (79)
6c (70)
6d (91)
6e (76)
6f (96)
6g (35)
6h (47)
6i (41)
6j (39)
6k (57)
6l (40)
The melting points were measured on an Electrothermal melt-
ing point apparatus and are uncorrected. TLC analyses were carried
out on Merck silica gel 60F254 and spots were visualized under UV
light. Chromatography on silica gel was carried out on Merck silica
(70–230 mesh ASTM). IR spectra were determined on a Nicolet
Magna 550 FTIR spectrometer using KBr discs. 1H NMR spectra
were recorded on a Varian 300 spectrometer in CDCl3 at 300 MHz.
All chemical shifts are given in parts per million (ppm) using dH
Me4Si¼0 ppm as reference and J values are given in hertz. 13C NMR
spectra were run in the same instrument at 75.4 MHz using the
solvent peak as internal reference. Low resolution mass spectra
were recorded on a ThermoQuest Polaris Q mass spectrometer
9
10
11
12
5l
a
Method A: DABCO/methyl acrylate; method B: DMAP/methyl vinyl ketone.
Isolated yields of 5g–l were not determined due to the instability.
Two step yields of 6g–l based on 4a–f.
b
c

S.P. Park et al. / Tetrahedron 65 (2009) 4703–4708
4705
operating at 70 eV. Elemental analyses were carried out on
a Thermo Electron Corporation Flash EA 1112 instrument. All re-
agents were used as received. 2,5-Dimethoxytetrahydrofuran,
methyl 2-aminobenzoate (1a), methyl 2-amino-5-bromobenzoate
(1b), methyl 2-aminio-4-chlorobenzoate (1c), methyl 2-amino-5-
fluorobenzoate (1d), and 2-chloro-5-nitrobenzaldehyde (7) are
commercially available (Aldrich). The known methyl 2-amino-5-
methoxybenzoate (1e),11 methyl 2-(1H-pyrrol-1-yl)benzoate (2a),2
methyl 4-chloro-2-(1H-pyrrol-1-yl)benzoate(2c),7d 2-(1H-pyrrol-
1 M THF solution of LAH (14 mL, 14 mmol). After 0.5–1 h, the
unreacted LAH was cautiously quenched with ethyl acetate and
a few drops of 15% sulfuric acid. The mixture was then extracted
with ethyl acetate and the organic layer was evaporated to dryness
to give crude product, which was purified by column chromatog-
raphy with silica gel by elution with hexane and ethyl acetate (6:1
to 3:1) to produce the pure product 3.
4.3.1. 5-Bromo-2-(1H-pyrrol-1-yl)phenylmethanol (3b)
1-yl)phenylmethanol
(3a),2
4-chloro-2-(1H-pyrrol-1-yl)phe-
Reaction time: 30 min; yield: 85%; white solid: mp 90–92 ꢀC
nylmethanol (3c),7d 2-(1H-pyrrol-1-yl)benzaldehyde (4a),2 and 4-
chloro-2-(1H-pyrrol-1-yl)benzaldehyde (4c)7d were prepared
according to the reported procedures.
(hexane–EtOAc); IR (neat) 3322 cmꢂ1 1H NMR (CDCl3)
; d 1.67 (t,
J¼5.8 Hz, 1H, OH), 4.54 (d, J¼5.8 Hz, 2H, CH2), 6.33 (t, J¼2.1 Hz, 2H,
pyrrole), 6.81 (t, J¼2.1 Hz, 2H, pyrrole), 7.17 (d, J¼8.2 Hz, 1H, aro-
matic), 7.49 (dd, J¼8.2 and 2.4 Hz, 1H, aromatic), 7.74 (d, J¼2.4 Hz,
4.2. General procedure for the synthesis of methyl 2-(1H-
pyrrol-1-yl)benzoates 2
1H, aromatic); 13C NMR (CDCl3)
d 60.7,109.7,121.5,122.2,128.1,131.4,
131.9, 138.1, 138.5; EIMS: m/z (%) 253 (31), 251 (31) [Mþ], 235 (19),
233 (22), 154 (100), 143 (34), 115 (26). Anal. Calcd for C11H10BrNO:
C, 52.41; H, 4.00; N, 5.56. Found: C, 52.51; H, 4.06; N, 5.68.
2,5-Dimethoxytetrahydrofuran (4.76 g, 36 mmol) was added to
a well stirred solution of methyl 2-aminobenzoate 1 (30 mmol) in
15 mL of glacial acetic acid. The clear solution was heated at reflux
for 1–4 h, and then the acetic acid was removed by evaporation at
reduced pressure. The mixture was poured over saturated aq
NaHCO3 solution and extracted with ethyl acetate (3ꢁ20 mL). After
drying over anhydrous MgSO4 and evaporation of the solvent under
reduced pressure, the crude compound was subjected to column
chromatography with silica gel by elution with hexane and ethyl
acetate (15:1). The fractions containing the pure compound were
combined and evaporated under reduced pressure to afford 2.
4.3.2. 5-Fluoro-2-(1H-pyrrol-1-yl)phenylmethanol (3d)
Reaction time: 30 min; yield: 95%; white solid: mp 36–38 ꢀC
(hexane–EtOAc); IR (neat) 3402 cmꢂ1; 1H NMR (CDCl3)
d 1.76 (s, 1H,
OH), 4.51 (s, 2H, CH2), 6.32 (t, J¼2.1 Hz, 2H, pyrrole), 6.77 (t,
J¼2.1 Hz, 2H, pyrrole), 7.00–7.07 (m, 1H, aromatic), 7.25–7.32 (m,
2H, aromatic); 13C NMR (CDCl3)
d
60.7, 109.4, 114.9 (d, JCF¼21.9 Hz),
115.3 (d, JCF¼23.1 Hz),122.4,128.3 (d, JCF¼8.5 Hz),135.3,138.9,162.0
(d, JCF¼246.6 Hz); EIMS: m/z (%) 191 (83) [Mþ], 173 (100), 162 (32),
148 (18). Anal. Calcd for C11H10FNO: C, 69.10; H, 5.27; N, 7.33.
Found: C, 69.22; H, 5.14; N, 7.17.
4.2.1. Methyl 5-bromo-2-(1H-pyrrol-1-yl)benzoate (2b)
Reaction time: 4 h; yield: 95%; white solid: mp 43–45 ꢀC (hex-
4.3.3. 5-Methoxy-2-(1H-pyrrol-1-yl)phenylmethanol (3e)
ane–EtOAc); IR (KBr) 1728 cmꢂ1
;
1H NMR (CDCl3)
d
3.72 (s, 3H,
Reaction time: 1 h; yield: 97%; white solid: mp 90–93 ꢀC (hex-
CH3), 6.32 (t, J¼2.1 Hz, 2H, pyrrole), 6.77 (t, J¼2.1 Hz, 2H, pyrrole),
ane–EtOAc); IR (neat) 3212 cmꢂ1; 1H NMR (CDCl3)
d 1.71 (s,1H, OH),
7.26 (d, J¼8.5 Hz, 1H, aromatic), 7.67 (dd, J¼8.5 and 2.4 Hz, 1H, ar-
3.85 (s, 3H, OCH3), 4.47 (s, 2H, CH2), 6.30 (t, J¼2.1 Hz, 2H, pyrrole),
6.77 (t, J¼2.1 Hz, 2H, pyrrole), 6.86 (dd, J¼8.5 and 2.7 Hz, 1H, aro-
matic), 7.06 (d, J¼2.7 Hz, 1H, aromatic), 7.21 (d, J¼8.5 Hz, 1H, aro-
omatic), 7.93 (d, J¼2.4 Hz, 1H, aromatic); 13C NMR (CDCl3)
d 52.6,
110.0, 120.4, 121.8, 128.2, 129.2, 133.3, 135.1, 139.3, 166.0; EIMS: m/z
(%) 281 (78), 279 (83) [Mþ], 249 (34), 247 (25), 223 (96), 221 (100),
142 (36), 140 (22),115 (52). Anal. Calcd for C12H10BrNO2: C, 51.45; H,
3.60; N, 5.00. Found: C, 51.60; H, 3.73; N, 4.86.
matic); 13C NMR (CDCl3)
d 55.5, 61.3, 109.0, 113.5, 113.6, 122.6, 127.9,
132.6, 137.9, 159.1; EIMS: m/z (%) 203 (100) [Mþ], 185 (32), 160 (31),
115 (20). Anal. Calcd for C12H13NO2: C, 70.92; H, 6.45; N, 6.89.
Found: C, 70.69; H, 6.52; N, 6.97.
4.2.2. Methyl 5-fluoro-2-(1H-pyrrol-1-yl)benzoate (2d)
Reaction time: 1 h; yield: 99%; yellow oil; IR (neat) 1726 cmꢂ1
;
4.4. General procedure for the synthesis of 2-(1H-pyrrol-
1-yl)benzaldehydes 4
1H NMR (CDCl3)
d
3.71 (s, 3H, CH3), 6.30 (t, J¼2.1 Hz, 2H, pyrrole),
6.76 (t, J¼2.1 Hz, 2H, pyrrole), 7.22–7.28 (m, 1H, aromatic), 7.36 (dd,
J¼8.9 and 4.9 Hz, 1H, aromatic), 7.51 (dd, J¼8.5 and 3.1 Hz, 1H, ar-
To a stirred solution of 2-(1H-pyrrol-1-yl)phenylmethanol 3
(10 mmol) in CH2Cl2 (60 mL) containing Celite (20 g) was added
PCC (6.25 g, 29 mmol) portionwise. After 40–60 min, the mixture
was filtered by suction. The filtrate was washed with 5% hydro-
chloric acid and then brine, dried over anhydrous MgSO4, and
evaporated. The residue was purified by column chromatography
with silica gel by elution with hexane and ethyl acetate (10:1 to 6:1)
to produce the aldehyde 4.
omatic); 13C NMR (CDCl3)
d
52.6, 109.6, 117.3 (d, JCF¼25.6 Hz), 119.1
(d, JCF¼21.9 Hz), 122.2, 128.8 (d, JCF¼8.5 Hz), 136.6, 160.9 (d,
JCF¼249.0 Hz), 165.9; EIMS: m/z (%) 219 (74) [Mþ], 161 (100), 134
(32), 133 (60). Anal. Calcd for C12H10FNO2: C, 65.75; H, 4.60; N, 6.39.
Found: C, 65.58; H, 4.49; N, 6.27.
4.2.3. Methyl 5-methoxy-2-(1H-pyrrol-1-yl)benzoate (2e)
Reaction time: 4 h; yield: 69%; yellow oil; IR (neat) 1721 cmꢂ1
;
1H NMR (CDCl3)
d
3.69 (s, 3H, CH3), 3.87 (s, 3H, OCH3), 6.28 (t,
4.4.1. 5-Bromo-2-(1H-pyrrol-1-yl)benzaldehyde (4b)
J¼2.1 Hz, 2H, pyrrole), 6.75 (t, J¼2.1 Hz, 2H, pyrrole), 7.06 (dd, J¼8.5
Reaction time: 1 h; yield: 79%; yellow oil; IR (neat) 1686 cmꢂ1
;
and 2.7 Hz, 1H, aromatic), 7.29 (d, J¼8.5 Hz, 1H, aromatic), 7.31 (d,
1H NMR (CDCl3)
d
6.41 (t, J¼2.1 Hz, 2H, pyrrole), 6.90 (t, J¼2.1 Hz,
J¼2.7 Hz, 1H, aromatic); 13C NMR (CDCl3)
d
52.4, 55.7, 109.1, 114.7,
2H, pyrrole), 7.33 (d, J¼8.5 Hz, 1H, aromatic), 7.79 (dd, J¼8.5 and
2.4 Hz, 1H, aromatic), 8.11 (d, J¼2.4 Hz, 1H, aromatic), 9.75 (s, 1H,
118.1, 122.3, 128.3, 128.9, 133.5, 158.3, 167.0; EIMS: m/z (%) 231 (100)
[Mþ], 199 (62), 184 (83), 158 (46). Anal. Calcd for C13H13NO3: C,
67.52; H, 5.67; N, 6.02. Found: C, 67.34; H, 5.73; N, 5.81.
CHO); 13C NMR (CDCl3)
d 111.1, 121.6, 123.6, 128.1, 131.1, 131.9, 137.4,
142.6, 188.5; EIMS: m/z (%) 251 (19), 249 (19) [Mþ], 223 (62), 221
(64), 142 (36), 115 (100). Anal. Calcd for C11H8BrNO: C, 52.83; H,
3.22; N, 5.60. Found: C, 52.78; H, 3.07; N, 5.36.
4.3. General procedure for the synthesis of 2-(1H-pyrrol-
1-yl)phenylmethanol 3
4.4.2. 5-Fluoro-2-(1H-pyrrol-1-yl)benzaldehyde (4d)
To an ice-cooled stirred solution of methyl 2-(1H-pyrrol-1-
yl)benzoate 2 (7.26 mmol) in dry THF (30 mL) was added dropwise
Reaction time: 1 h; yield: 76%; yellow oil; IR (neat) 1693 cmꢂ1
;
1H NMR (CDCl3)
d
6.39 (t, J¼2.1 Hz, 2H, pyrrole), 6.90 (t, J¼2.1 Hz,

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S.P. Park et al. / Tetrahedron 65 (2009) 4703–4708
2H, pyrrole), 7.33–7.47 (m, 2H, aromatic), 7.64–7.68 (m, 1H, aro-
matic), 9.69 (s, 1H, CHO); 13C NMR (CDCl3)
110.7, 114.2 (d,
JCF¼23.2 Hz), 121.7 (d, JCF¼23.2 Hz), 123.9, 128.7 (d, JCF¼8.5 Hz),
132.5, 140.1, 161.6 (d, JCF¼250.3 Hz), 188.8; EIMS: m/z (%) 189 (71)
[Mþ], 161 (100), 134 (39), 133 (82). Anal. Calcd for C11H8FNO: C,
69.83; H, 4.26; N, 7.40. Found: C, 70.01; H, 4.17; N, 7.25.
pyrrole), 7.25–7.55 (m, 4H, aromatic); 13C NMR (CDCl3)
d 51.9, 67.7,
d
109.1, 122.6, 126.4, 127.2, 127.6, 128.1, 128.6, 136.8, 139.7, 141.4,
166.4; EIMS: m/z (%) 239 (14), 238 (16), 224 (17),198 (100),180 (40),
168 (24), 154 (27), 115 (15). Anal. Calcd for C15H15NO3: C, 70.02; H,
5.88; N, 5.44. Found: C, 69.87; H, 5.65; N, 5.20.
4.5.2. Methyl 2-[1-hydroxy-1-{5-bromo-2-(1H-pyrrol-1-
yl)phenyl}methyl]propenoate (5b)
4.4.3. 5-Methoxy-2-(1H-pyrrol-1-yl)benzaldehyde (4e)
Reaction time: 40 min; yield: 82%; yellow oil; IR (neat)
Reaction time: 2 days; yield: 82%; yellow oil; IR (neat) 3443,
1686 cmꢂ1
;
1H NMR (CDCl3)
d
3.90 (s, 3H, OCH3), 6.37 (t, J¼2.1 Hz,
1720, 1631, 1496 cmꢂ1; 1H NMR (CDCl3)
d
2.97 (d, J¼5.5 Hz, 1H, OH),
2H, pyrrole), 6.88 (t, J¼2.1 Hz, 2H, pyrrole), 7.20 (dd, J¼8.5 and
3.0 Hz, 1H, aromatic), 7.36 (d, J¼8.5 Hz, 1H, aromatic), 7.45 (d,
3.71 (s, 3H, OCH3), 5.54 (d, J¼5.5 Hz,1H, CH), 5.65 (s,1H, CH), 6.30 (t,
J¼2.1 Hz, 2H, pyrrole), 6.33 (s, 1H, CH), 6.78 (t, J¼2.1 Hz, 2H, pyr-
role), 7.15 (d, J¼8.5 Hz, 1H, aromatic), 7.49 (dd, J¼8.5 and 2.4 Hz, 1H,
J¼3.0 Hz, 1H, aromatic), 9.68 (s, 1H, CHO); 13C NMR (CDCl3)
d 55.8,
110.0, 110.1, 122.0, 124.0, 128.2, 131.9, 137.5, 158.9, 189.9; EIMS: m/z
(%) 201 (41) [Mþ], 173 (65), 158 (100), 130 (72). Anal. Calcd for
C12H11NO2: C, 71.63; H, 5.51; N, 6.96. Found: C, 71.44; H, 5.55; N, 7.15.
aromatic), 7.68 (d, J¼2.4 Hz, 1H, aromatic); 13C NMR (CDCl3)
d 52.1,
67.6, 109.6, 121.9, 122.5, 126.9, 128.9, 130.8, 131.8, 138.7, 139.0, 140.8,
166.3; EIMS: m/z (%) 258 (25), 197 (63), 179 (65), 169 (79), 167 (100),
154 (44),141 (34),115 (56). Anal. Calcd for C15H14BrNO3: C, 53.59; H,
4.20; N, 4.17. Found: C, 53.31; H, 4.03; N, 4.31.
4.4.4. 5-Nitro-2-(1H-pyrrol-1-yl)benzaldehyde (4f)
Aldehyde 4f was prepared from 2-chloro-5-nitrobenzaldehyde
(7) with pyrrole according to the reported procedure.9 In a Schlenck
tube, 2-chloro-5-nitrobenzaldehyde (7, 401 mg, 2.17 mmol), pyrrole
(133 mg, 1.97 mmol), palladium acetate (4.4 mg, 0.02 mmol), xant-
phos (34 mg, 0.059 mmol), and potassium carbonate (817 mg,
5.91 mmol) were mixed in 5 mL of o-xylene. The mixture was
degassed and the tube refilled with argon. After heating at 120 ꢀC for
13 h, the mixture was cooled to room temperature, washed with
water, and extracted with ethyl acetate. The combined organic
extracts were dried over anhydrous MgSO4 and concentrated under
reduced pressure. The residue was purified by column chromato-
graphy with silica gel byelutionwith hexane and ethyl acetate (10:1)
providing 155 mg (33%) of 4f as a yellow solid: mp 57–59 ꢀC (hex-
4.5.3. Methyl 2-[1-hydroxy-1-{4-chloro-2-(1H-pyrrol-1-
yl)phenyl}methyl]propenoate (5c)
Reaction time: 3 days; yield: 88%; yellow oil; IR (neat) 3418,
1720, 1596, 1497 cmꢂ1; 1H NMR (CDCl3)
d
2.96 (d, J¼5.2 Hz, 1H, OH),
3.70 (s, 3H, OCH3), 5.55 (d, J¼5.2 Hz, 1H, CH), 5.62 (s, 1H, CH), 6.30
(m, 3H, CH and pyrrole), 6.81 (dd, J¼8.5 and 2.1 Hz, 1H, aromatic),
7.28 (d, J¼2.1 Hz, 1H, aromatic), 7.38 (t, J¼2.1 Hz, 2H, pyrrole), 7.49
(d, J¼8.5 Hz, 1H, aromatic); 13C NMR (CDCl3)
d 52.0, 67.6, 109.7,
122.4, 126.6, 127.3, 128.2, 129.0, 134.0, 135.4, 140.7, 141.0, 166.4;
EIMS: m/z (%) 273 (19), 234 (31), 232 (100), 216 (28), 214 (46), 188
(25),167 (33). Anal. Calcd for C15H14ClNO3: C, 61.76; H, 4.84; N, 4.80.
Found: C, 61.49; H, 4.73; N, 4.54.
ane–EtOAc); IR (neat) 1694 cmꢂ1; 1H NMR (CDCl3)
d
6.50 (t, J¼2.1 Hz,
2H, pyrrole), 6.99 (t, J¼2.1 Hz, 2H, pyrrole), 7.64 (d, J¼8.5 Hz, 1H,
4.5.4. Methyl 2-[1-hydroxy-1-{5-fluoro-2-(1H-pyrrol-
1-yl)phenyl}methyl]propenoate (5d)
aromatic), 8.52 (dd, J¼8.5 and 2.4 Hz, 1H, aromatic), 8.84 (d,
J¼2.4 Hz, 1H, aromatic), 9.98 (s, 1H, CHO); 13C NMR (CDCl3)
d
112.5,
Reaction time: 3 days; yield: 90%; yellow oil; IR (neat) 3437,1721,
123.4,124.4,126.9,128.8,130.2,146.2,147.7,187.7; EIMS: m/z (%) 216
(37) [Mþ],188 (100), 158 (40),115 (76). Anal. Calcd for C11H8N2O3: C,
61.11; H, 3.73; N, 12.96. Found: 61.01; H, 3.85; N, 12.89.
1629, 1505 cmꢂ1; 1H NMR (CDCl3)
(s, 3H, OCH3), 5.50 (d, J¼5.0 Hz, 1H, CH), 5.61 (s, 1H, CH), 6.29 (t,
J¼2.1 Hz, 2H, pyrrole), 6.31 (s,1H, CH), 6.77 (t, J¼2.1 Hz, 2H, pyrrole),
7.02–7.09 (m, 1H, aromatic), 7.25–7.28 (m, 2H, aromatic); 13C NMR
d
3.07 (d, J¼5.0 Hz, 1H, OH), 3.71
4.5. General procedure for the synthesis of the
Morita–Baylis–Hillman adducts 5
(CDCl3)
d
52.1, 67.8, 109.3, 114.5 (d, JCF¼23.2 Hz), 115.5 (d,
JCF¼23.2 Hz), 122.7, 126.9, 129.1 (d, JCF¼8.5 Hz), 135.6, 139.6 (d,
JCF¼7.3 Hz), 140.7, 162.0 (d, JCF¼247.8 Hz), 166.3; EIMS: m/z (%) 257
(6), 216 (100),198 (39),186 (27),172 (29). Anal. Calcd for C15H14FNO3:
C, 65.45; H, 5.13; N, 5.09. Found: C, 65.22; H, 4.88; N, 4.81.
Method A. A mixture of 2-(1H-pyrrol-1-yl)benzaldehyde 4a–f
(10 mmol), methyl acrylate (2.58 g, 30 mmol), DABCO (1.12 g,
10 mmol), and triethanolamine (1.19 g, 8 mmol) without solvent
was stirred at room temperature for 7 h to 3 days. The reaction
mixture was diluted with water (20 mL) and extracted with ethyl
acetate (3ꢁ40 mL). The combined organic layers were dried over
anhydrous MgSO4 and the solvent was evaporated in vacuo. The
resulting mixture was chromatographed on silica gel eluting with
hexane and ethyl acetate (6:1 to 3:1) to produce 5a–f as an oil.
Method B. A mixture of 2-(1H-pyrrol-1-yl)benzaldehyde 4a–f
(10 mmol), methyl vinyl ketone (1.40 g, 20 mmol), and DMAP
(0.11 g, 1 mmol) in 15 mL of DMF was stirred at room temperature
for 1–20 days. The reaction mixture was diluted with water (20 mL)
and extracted with ethyl ether (3ꢁ40 mL). The combined organic
layers were dried over anhydrous MgSO4 and solvent was evapo-
rated in vacuo to afford the crude Morita–Baylis–Hillman adduct
5g–l, which was subjected to next step without purification.
4.5.5. Methyl 2-[1-hydroxy-1-{5-methoxy-2-(1H-pyrrol-
1-yl)phenyl}methyl]propenoate (5e)
Reaction time: 3 days; yield: 75%; yellow oil; IR (neat) 3465,
1721, 1610, 1508 cmꢂ1; 1H NMR (CDCl3)
d
2.98 (d, J¼5.2 Hz, 1H, OH),
3.70 (s, 3H, OCH3), 3.84 (s, 3H, OCH3), 5.48 (d, J¼5.2 Hz, 1H, CH),
5.62 (s, 1H, CH), 6.27 (t, J¼2.1 Hz, 2H, pyrrole), 6.29 (s, 1H, CH), 6.75
(t, J¼2.1 Hz, 2H, pyrrole), 6.88 (dd, J¼8.5 and 3.1 Hz, 1H, aromatic),
7.05 (d, J¼2.7 Hz, 1H, aromatic), 7.23 (d, J¼8.5 Hz, 1H, aromatic); 13C
NMR (CDCl3) d 52.0, 55.5, 67.9,108.8,112.4,113.9,122.8,126.6,128.5,
132.7, 138.4, 141.2, 159.2, 166.5; EIMS: m/z (%) 228 (100), 210 (28),
198 (21), 167 (13). Anal. Calcd for C16H17NO4: C, 66.89; H, 5.96; N,
4.88. Found: C, 66.72; H, 5.70; N, 4.63.
4.5.6. Methyl 2-[1-hydroxy-1-{5-nitro-2-(1H-pyrrol-
1-yl)phenyl}methyl]propenoate (5f)
4.5.1. Methyl 2-[1-hydroxy-1-{2-(1H-pyrrol-1-
yl)phenyl}methyl]propenoate (5a)
Reaction time: 7 h; yield: 98%; yellow oil; IR (neat) 3440, 1715,
1615,1588,1529,1497 cmꢂ1; 1H NMR (CDCl3)
d
3.14 (d, J¼5.2 Hz,1H,
Reaction time: 3 days; yield: 82%; yellow oil; IR (neat) 3436,
OH), 3.71 (s, 3H, OCH3), 5.72 (s, 1H, CH), 5.75 (d, J¼5.2 Hz, 1H, CH),
6.37 (t, J¼2.1 Hz, 2H, pyrrole), 6.39 (s, 1H, CH), 6.89 (t, J¼2.1 Hz, 2H,
pyrrole), 7.45 (d, J¼8.5 Hz, 1H, aromatic), 8.24 (dd, J¼8.5 and 2.4 Hz,
1H, aromatic), 8.45 (d, J¼2.4 Hz, 1H, aromatic); 13C NMR (CDCl3)
1722, 1630, 1501 cmꢂ1; 1H NMR (CDCl3)
3.67 (s, 3H, OCH3), 5.57 (d, J¼5.5 Hz,1H, CH), 5.64 (s,1H, CH), 6.29 (t,
J¼2.1 Hz, 2H, pyrrole), 6.30 (s, 1H, CH), 6.82 (t, J¼2.1 Hz, 2H,
d
3.02 (d, J¼5.5 Hz, 1H, OH),

S.P. Park et al. / Tetrahedron 65 (2009) 4703–4708
4707
d
52.2, 67.6, 110.7, 122.3, 123.8, 123.9, 127.3, 127.8, 138.1, 140.4, 144.8,
OCH3), 6.00 (dd, J¼3.1 and 1.5 Hz, 1H, pyrrole), 6.30 (dd, J¼3.1 and
3.1 Hz, 1H, pyrrole), 6.92 (dd, J¼3.1 and 1.5 Hz, 1H, pyrrole), 7.07–7.17
(m, 2H, aromatic), 7.45–7.49 (m, 1H, aromatic), 7.53 (s, 1H, CH); 13C
146.9, 166.1; EIMS: m/z (%) 243 (86), 225 (33), 197 (100), 179 (20),
167 (31). Anal. Calcd for C15H14N2O5: C, 59.60; H, 4.67; N, 9.27.
Found: C, 59.78; H, 4.39; N, 8.98.
NMR (CDCl3)
d
24.7, 52.4, 105.7, 111.0, 117.0 (d, JCF¼18.3 Hz), 117.3 (d,
JCF¼18.3 Hz), 120.4, 125.1 (d, JCF¼8.5 Hz), 129.6 (d, JCF¼7.3 Hz), 134.1,
135.5,135.9 (two),159.6 (d, JCF¼245.4 Hz),166.1; EIMS: m/z(%) 257 (49)
[Mþ], 256 (72), 242 (79), 198 (100), 196 (36). Anal. Calcd for
C15H12FNO2: C, 70.03; H, 4.70; N, 5.44. Found: C.69.85; H, 4.92; N, 5.23.
4.6. General procedure for the synthesis of 4H-pyrrolo-
[1,2-a][1]benzazepines 6
Method A. To a stirred solution of the Morita–Baylis–Hillman
adduct 5a–f (2 mmol) in 5 mL of CCl4 was added dropwise 95%
H2SO4 (1.18 g, 12 mmol) at room temperature. After 10 min, the
mixture was quenched with water (5 mL) and dichloromethane
(10 mL), and then extracted with dichloromethane (3ꢁ20 mL). The
organic layer was dried over anhydrous MgSO4 and the solvent
evaporated under reduced pressure. The resulting mixture was
chromatographed on silica gel eluting with hexane and ethyl ace-
tate (10:1 to 4:1) to give 6a–f as a yellow solid.
Method B. To a stirred solution of the crude Morita–Baylis–
Hillman adduct 5g–l, which was obtained from aldehyde 4a–f
(10 mmol) and methyl vinyl ketone (20 mmol) in 20 mL of CCl4, was
added dropwise 95% H2SO4 (5.88 g, 60 mmol) at room temperature.
After 10 min, the mixture was quenched with water (10 mL) and
dichloromethane (20 mL). The work-up procedure was the same as
above to give 6g–l as a yellow solid.
4.6.5. Methyl 8-methoxy-4H-pyrrolo[1,2-a][1]benzazepine-5-
carboxylate (6e)
Yield: 76%; yellow solid: mp 80–82 ꢀC (hexane–EtOAc); IR (KBr)
1708, 1634, 1502 cmꢂ1; 1H NMR (CDCl3)
d 3.59 (s, 2H, CH2), 3.83 (s,
3H, OCH3), 3.85 (s, 3H, OCH3), 5.98 (d, J¼3.4 and 1.8 Hz,1H, pyrrole),
6.28 (dd, J¼3.4 and 3.1 Hz, 1H, pyrrole), 6.89 (d, J¼3.1 Hz, 1H, aro-
matic), 6.92 (dd, J¼3.1 and 1.8 Hz, 1H, pyrrole), 7.00 (dd, J¼8.9 and
3.1 Hz, 1H, aromatic), 7.44 (d, J¼8.9 Hz, 1H, aromatic), 7.58 (s, 1H,
CH); 13C NMR (CDCl3)
d 24.7, 52.3, 55.6, 105.1, 110.4, 115.1, 116.5,
120.1, 124.6, 129.0, 133.2 (two), 135.3, 137.1, 156.7, 166.4; EIMS: m/z
(%) 269 (62) [Mþ], 268 (97), 254 (100), 225 (50), 210 (52), 167 (52).
Anal. Calcd for C16H15NO3: C, 71.36; H, 5.61; N, 5.20. Found: C, 71.15;
H, 5.49; N, 5.02.
4.6.6. Methyl 8-nitro-4H-pyrrolo[1,2-a][1]benzazepine-5-
carboxylate (6f)
4.6.1. Methyl 4H-pyrrolo[1,2-a][1]benzazepine-5-carboxylate (6a)
Yield: 96%; yellow solid: mp 158–160 ꢀC (hexane–EtOAc); IR
Yield: 79%; yellow solid: mp 67–68 ꢀC (hexane–EOAc); IR (KBr)
(KBr) 1712, 1641, 1578, 1521, 1490 cmꢂ1 1H NMR (CDCl3)
; d 3.65 (s,
1709, 1634, 1491 cmꢂ1; 1H NMR (CDCl3)
d
3.61 (s, 2H, CH2), 3.83 (s,
2H, CH2), 3.86 (s, 3H, OCH3), 6.07 (dd, J¼3.4 and 1.8 Hz, 1H, pyrrole),
6.39 (dd, J¼3.4 and 3.4 Hz, 1H, pyrrole), 7.01 (dd, J¼3.4 and 1.8 Hz,
1H, pyrrole), 7.63 (d, J¼8.5 Hz, 1H, aromatic), 7.64 (s, 1H, CH), 8.27
(dd, J¼8.5 and 2.4 Hz, 1H, aromatic), 8.31 (d, J¼2.4 Hz, 1H, aro-
3H, OCH3), 6.00 (dd, J¼3.4 and 1.8 Hz, 1H, pyrrole), 6.31 (dd, J¼3.4
and 3.4 Hz, 1H, pyrrole), 6.97 (dd, J¼3.4 and 1.8 Hz, 1H, pyrrole),
7.26–7.53 (m, 4H, aromatic), 7.63 (s, 1H, CH); 13C NMR (CDCl3)
d
24.7, 52.3, 105.7, 110.9, 120.3, 123.3, 125.1, 128.0, 130.0, 131.7, 132.8,
matic); 13C NMR (CDCl3)
d 24.7, 52.6, 107.6, 112.8, 120.7, 124.1, 124.7,
135.7, 137.3, 139.5, 166.4; EIMS: m/z (%) 239 (65) [Mþ], 238 (95), 224
(91), 180 (100), 178 (43), 152 (27). Anal. Calcd for C15H13NO2: C,
75.30; H, 5.48; N, 5.85. Found: C, 75.12; H, 5.25; N, 5.63.
127.4, 128.3, 135.0, 135.3, 135.8, 144.0, 144.3, 165.8; EIMS: m/z (%)
284 (73) [Mþ], 283 (65), 269 (100), 237 (66), 225 (51), 223 (48), 179
(47), 178 (52). Anal. Calcd for C15H12N2O4: C, 63.38; H, 4.25; N, 9.85.
Found: C, 63.22; H, 4.07; N, 9.57.
4.6.2. Methyl 8-bromo-4H-pyrrolo[1,2-a][1]benzazepine-5-
carboxylate (6b)
4.6.7. 5-Acetyl-4H-pyrrolo[1,2-a][1]benzazepine (6g)
Yield: 79%; yellow solid: mp 92–94 ꢀC (hexane–EtOAc); IR (KBr)
Two steps yield: 35%; yellow solid: mp 63–65 ꢀC (hexane–
1711, 1634, 1488 cmꢂ1; 1H NMR (CDCl3)
d
3.60 (s, 2H, CH2), 3.83 (s,
EtOAc); IR (KBr) 1665, 1625, 1492 cmꢂ1 1H NMR (CDCl3)
; d 2.46 (s,
3H, OCH3), 6.01 (dd, J¼3.4 and 1.8 Hz, 1H, pyrrole), 6.32 (dd, J¼3.4
and 3.1 Hz, 1H, pyrrole), 6.93 (dd, J¼3.1 and 1.8 Hz, 1H, pyrrole),
7.36–7.39 (m, 1H, aromatic), 7.51–7.54 (m, 3H, aromatic); 13C NMR
3H, CH3), 3.58 (s, 2H, CH2), 5.99 (dd, J¼3.4 and 1.8 Hz, 1H, pyrrole),
6.31 (dd, J¼3.4 and 3.1 Hz, 1H, pyrrole), 6.98 (dd, J¼3.1 and 1.8 Hz,
1H, pyrrole), 7.28–7.55 (m, 4H, aromatic), 7.47 (s, 1H, CH); 13C NMR
(CDCl3)
d
24.7, 52.4, 106.1, 111.4, 118.3, 120.2, 125.0, 129.7, 132.8,
(CDCl3) d 22.7, 25.3, 105.7, 111.0, 120.1, 123.4, 125.1, 127.9, 130.3,
134.0, 134.1, 135.5, 135.7, 138.5, 166.1; EIMS: m/z (%) 319 (52), 318
(77), 317 (52) [Mþ], 316 (72), 304 (78), 302 (84), 260 (48), 258 (52),
179 (100). Anal. Calcd for C15H12BrNO2: C, 56.62; H, 3.80; N, 4.40.
Found: C, 56.79; H, 3.58; N: 4.21.
131.6, 135.7, 137.7, 139.6, 141.7, 196.4; EIMS: m/z (%) 223 (37) [Mþ],
222 (42), 180 (100), 152 (14). Anal. Calcd for C15H13NO: C, 80.69; H,
5.87; N, 6.27. Found: C, 80.52; H, 5.60; N, 6.05.
4.6.8. 5-Acetyl-8-bromo-4H-pyrrolo[1,2-a][1]benzazepine (6h)
4.6.3. Methyl 9-chloro-4H-pyrrolo[1,2-a][1]benzazepine-5-
carboxylate (6c)
Two steps yield: 47%; yellow solid: mp 156–158 ꢀC (hexane–
EtOAc); IR (KBr) 1666,1628,1488 cmꢂ1; 1H NMR (CDCl3)
d 2.45 (s, 3H,
Yield: 70%; yellow solid: mp 96–98 ꢀC (hexane–EtOAc); IR (KBr)
CH3), 3.57 (s, 2H, CH2), 5.99 (dd, J¼3.4and1.8 Hz,1H, pyrrole), 6.31(dd,
J¼3.4 and 3.1 Hz, 1H, pyrrole), 6.93 (dd, J¼3.1 and 1.8 Hz, 1H, pyrrole),
7.36 (s, 1H, CH), 7.39 (d, J¼8.2 Hz, 1H, aromatic), 7.56 (d, J¼8.2 Hz, 1H,
1712, 1634, 1487 cmꢂ1; 1H NMR (CDCl3)
d 3.60 (s, 2H, CH2), 3.83 (s, 3H,
OCH3), 6.00 (dd, J¼3.4 and 1.8 Hz, 1H, pyrrole), 6.33 (dd, J¼3.4 and
3.1 Hz, 1H, pyrrole), 6.95 (dd, J¼3.1 and 1.8 Hz, 1H, pyrrole), 7.26 (dd,
J¼8.2 and 1.8 Hz,1H, aromatic), 7.33 (d, J¼8.2 Hz,1H, aromatic), 7.51 (d,
aromatic), 7.64 (s, 1H, aromatic); 13C NMR (CDCl3)
d 22.7, 25.3, 106.2,
111.5, 118.3, 120.0, 125.0, 129.7, 133.0, 134.0, 135.5, 136.0, 138.6, 142.7,
196.1; EIMS: m/z (%) 303 (38), 302 (47), 301 (40) [Mþ], 300 (45), 260
(97), 258 (100),179 (88),178(43). Anal.CalcdforC15H12BrNO:C, 59.62;
H, 4.00; N, 4.64. Found: C, 59.79; H, 3.81; N, 4.58.
J¼1.8 Hz, 1H, aromatic), 7.57 (s, 1H, CH); 13C NMR (CDCl3)
d 24.7, 52.4,
106.2, 111.4, 118.3, 120.3, 125.0, 129.7, 132.8, 134.0, 134.1, 135.5, 135.8,
138.5, 166.1; EIMS: m/z (%) 275 (17), 274 (30), 273 (55) [Mþ], 272 (69),
260 (28), 258 (92), 216 (34), 214 (100),178 (63),151 (19). Anal. Calcd for
C15H12ClNO2: C, 65.82; H, 4.42; N, 5.12. Found: C, 65.70; H, 4.22; N, 4.89.
4.6.9. 5-Acetyl-9-chloro-4H-pyrrolo[1,2-a][1]benzazepine (6i)
Two steps yield: 41%; yellow solid: mp 99–101 ꢀC (hexane–
4.6.4. Methyl 8-fluoro-4H-pyrrolo[1,2-a][1]benzazepine-5-
carboxylate (6d)
EtOAc); IR (KBr) 1665, 1629, 1594, 1489 cmꢂ1 1H NMR (CDCl3)
;
d
2.45 (s, 3H, CH3), 3.58 (s, 2H, CH2), 5.99 (dd, J¼3.4 and 1.8 Hz, 1H,
Yield: 91%; yellow solid: mp 70–72 ꢀC (hexane–EtOAc); IR (KBr)
pyrrole), 6.32 (dd, J¼3.4 and 3.4 Hz,1H, pyrrole), 6.95 (dd, J¼3.4 and
1712, 1637, 1498 cmꢂ1; 1H NMR (CDCl3)
d
3.60 (s, 2H, CH2), 3.83 (s, 3H,
1.8 Hz, 1H, pyrrole), 7.29–7.37 (m, 2H, aromatic), 7.40 (s, 1H, CH),

4708
S.P. Park et al. / Tetrahedron 65 (2009) 4703–4708
7.53 (s, 1H, aromatic); 13C NMR (CDCl3)
d
22.7, 25.3, 106.3, 111.6,
1H, aromatic), 8.30 (dd, J¼8.9 and 2.4 Hz, 1H, aromatic), 8.36 (d,
120.1, 123.4, 125.3, 126.4, 132.8, 135.6, 135.8, 136.6, 140.4, 141.8,
196.1; EIMS: m/z (%) 259 (6), 258 (11), 257 (22) [Mþ], 256 (22), 216
(33), 214 (100), 179 (35), 178 (35). Anal. Calcd for C15H12ClNO: C,
67.91; H, 4.69; N, 5.43. Found: C, 70.22; H, 4.48; N, 5.23.
J¼2.4 Hz, 1H, aromatic); 13C NMR (CDCl3)
d 22.7, 25.4, 107.7, 112.9,
120.5, 124.2, 124.9, 127.3, 128.3, 135.5, 135.9, 143.3, 144.1, 144.3,
195.9; EIMS: m/z (%) 268 (39) [Mþ], 267 (26), 225 (100), 221 (47),
179 (66), 178 (34). Anal. Calcd for C15H12N2O3: C, 67.16; H, 4.51; N,
10.44. Found: C, 66.88; H, 4.34; N, 10.16.
4.6.10. 5-Acetyl-8-fluoro-4H-pyrrolo[1,2-a][1]benzazepine (6j)
Two steps yield: 39%; yellow solid: mp 100–103 ꢀC (hexane–
Acknowledgements
EtOAc); IR (KBr) 1667, 1630, 1582, 1498 cmꢂ1 1H NMR (CDCl3)
;
d
2.45 (s, 3H, CH3), 3.57 (s, 2H, CH2), 6.00 (dd, J¼3.1 and 1.8 Hz, 1H,
This work was supported in part by Brain Korea 21 program,
Republic of Korea.
pyrrole), 6.31 (dd, J¼3.1 and 3.1 Hz, 1H, pyrrole), 6.93 (dd, J¼3.1 and
1.8 Hz, 1H, pyrrole), 7.10–7.20 (m, 2H, aromatic), 7.37 (s, 1H, CH),
7.49 (dd, J¼8.9 and 4.9 Hz, 1H, aromatic); 13C NMR (CDCl3)
d 22.7,
References and notes
25.3, 105.8, 111.1, 117.2 (d, JCF¼22.0 Hz), 117.3 (d, JCF¼22.0 Hz), 120.1,
125.2 (d, JCF¼8.5 Hz), 129.6 (d, JCF¼7.3 Hz), 135.5, 135.9, 136.2, 142.7,
159.6 (d, JCF¼246.6 Hz), 196; EIMS: m/z (%) 241 (28) [Mþ], 240 (32),
198 (100), 178 (10). Anal. Calcd for C15H12FNO: C, 74.67; H, 5.01; N,
5.81. Found: C, 74.48; H, 4.79; N, 5.70.
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350; (d) Langer, P. Angew. Chem., Int. Ed. 2000, 39, 3049–3052; (e) Basavaiah,
D.; Rao, A. J.; Satyanarayana, T. Chem. Rev. 2003, 103, 811–891; (f) Kataoka, T.;
Kinoshita, H. Eur. J. Org. Chem. 2005, 45–58; (g) Basavaiah, D.; Rao, K. V.; Reddy,
R. J. Chem. Soc. Rev. 2007, 36, 1581–1588; (h) Singh, V.; Batra, S. Tetrahedron
2008, 64, 4511–4574; (i) Declerck, V.; Martinez, J.; Lamaty, F. Chem. Rev. 2009,
109, 1–48.
Two steps yield: 57%; yellow solid: mp 62–64 ꢀC (hexane–
EtOAc); IR (KBr) 1664, 1628, 1608, 1502 cmꢂ1 1H NMR (CDCl3)
;
d
2.45 (s, 3H, CH3), 3.57 (s, 2H, CH2), 3.87 (s, 3H, OCH3), 5.96 (dd,
J¼3.1 and 1.8 Hz, 1H, pyrrole), 6.28 (dd, J¼3.1 and 3.1 Hz, 1H, pyr-
role), 6.90 (d, J¼2.7 Hz, 1H, aromatic), 6.93 (dd, J¼3.1 and 1.8 Hz,1H,
pyrrole), 7.02 (dd, J¼8.9 and 2.7 Hz, 1H, aromatic), 7.41 (s, 1H, CH),
7.45 (d, J¼8.9 Hz, 1H, aromatic); 13C NMR (CDCl3)
d 22.7, 25.4, 55.6,
105.2, 110.4, 115.1, 116.7, 119.9, 124.7, 128.9, 133.3, 135.3, 137.5, 141.9,
156.7, 196.4; EIMS: m/z (%) 253 (44) [Mþ], 252 (52), 210 (100), 167
(36). Anal. Calcd for C16H15NO2: C, 75.87; H, 5.97; N, 5.53. Found: C,
75.58; H, 5.73; N, 5.38.
5. Lim, H. N.; Ji, S.-H.; Lee, K.-J. Synthesis 2007, 2454–2460.
6. Jeon, K. J.; Lee, K.-J. J. Heterocycl. Chem. 2008, 45, 615–619.
7. (a) Kobayashi, K.; Nakahashi, R.; Takanohashi, A.; Kitamura, T.; Morikawa, O.;
Konishi, H. Chem. Lett. 2002, 624–625; (b) Kobayashi, K.; Takanohashi, A.; Ha-
shimoto, K.; Morikawa, O.; Konishi, H. Tetrahedron 2006, 62, 3158–3161; (c)
Kobayashi, K.; Takanohashi, A.; Hashimoto, K.; Morikawa, O.; Konishi, H. Tet-
rahedron 2006, 62, 10379–10382; (d) Kobayashi, K.; Himei, Y.; Fukamachi, S.;
Tanmatsu, M.; Morikawa, O.; Konishi, H. Tetrahedron 2007, 63, 4356–4359.
8. Josey, A. D.; Jenner, E. L. J. Org. Chem. 1962, 27, 2466–2470.
9. Wu, Y.; Lawson, P. V.; Henary, M. M.; Schmidt, K.; Bre´das, J.-U.; Fahrni, C. J.
J. Phys. Chem. A 2007, 111, 4584–4595.
4.6.12. 5-Acetyl-8-nitro-4H-pyrrolo[1,2-a][1]benzazepine (6l)
Two steps yield: 40%; yellow solid: mp 193–195 ꢀC (hexane–
EtOAc); IR (KBr) 1660, 1633, 1610, 1572, 1523, 1491 cmꢂ1 1H NMR
;
(CDCl3)
d
2.50 (s, 3H, CH3), 3.62 (s, 2H, CH2), 6.06 (dd, J¼3.4 and
10. Bras, J. L.; Muzart, J. Tetrahedron 2007, 63, 7942–7948.
11. Theeraladanon, C.; Arisawa, M.; Nishida, A.; Nakagawa, M. Tetrahedron 2004, 60,
3017–3035.
1.8 Hz, 1H, pyrrole), 6.39 (dd, J¼3.4 and 3.1 Hz, 1H, pyrrole), 7.01
(dd, J¼3.1 and 1.8 Hz, 1H, pyrrole), 7.49 (s, 1H, CH), 7.66 (d, J¼8.9 Hz,