Preparation of pyrrolo[2,1,5-cd]indolizine derivatives by intramolecular condensation of 3-acyl-5-methylindolizines

Article abstract of DOI:10.1002/jhet.5570380408

An efficient two step route has been developed to synthesize pyrrolo[2,1,5-cd]indolizine derivatives. The reaction sequence proceeds via preparation of 3-acyl-5-methylindolizines followed by an intramolecular condensation. The procedures were carried out

Full text of DOI:10.1002/jhet.5570380408

Jul-Aug 2001
Preparation of Pyrrolo[2,1,5-cd]indolizine Derivatives By
Intramolecular Condensation of 3-Acyl-5-Methylindolizines
Feng Liang [a], Jiaxin Hu [a], Lande Zhang [a], Yuefei Hu*[a,b] and Hongwen Hu[a,b]
853
Department of Chemistry [a] and Coordination Chemistry Institute [b],
Nanjing University, Nanjing 210093, People’s Republic of China
Received November 20, 2000
An efficient two step route has been developed to synthesize pyrrolo[2,1,5-cd]indolizine derivatives. The
reaction sequence proceeds via preparation of 3-acyl-5-methylindolizines followed by an intramolecular
condensation. The procedures were carried out under convenient conditions and gave the products in high
yields. It could be expected to be used to prepare a broad range of potentially interesting pyrrolo[2,1,5-
cd]indolizine derivatives.
J. Heterocyclic Chem., 38, 853 (2001).
Pyrrolo[2,1,5-cd]indolizine is the most interesting mem-
azaindolizine (1) under Vilsmeier conditions, even though
with very low yields (Scheme 1). Following that procedure,
a mixture of 5-methylindolizine-1-carbonitrile (4a) and
phosphorus oxychloride in N,N-dimethylformamide was
stirred at room temperature overnight. After normal work-
up, a white solid was obtained by recrystallization.
Unfortunately, it was not the expected product 1-cyanopy-
rrolo[2,1,5-cd]indolizine-4-carboxaldehyde (5) and its
structure was assigned as 1-cyano-5-methylindolizine-3-
ber in the family of cyclazines, well-known as
cycl[2,2,3]azine [1]. Its derivatives have received consid-
erable attention in the field of synthetic organic chemistry
due to their novel structural properties [1,2], increasing
biological interests [1,3] and because their partial saturated
frameworks occur in natural products [1,4] (Chart 1).
1
carboxaldehyde (6a) by its ir, H nmr and mass spec-
troscopy. This result may reason the fact that 5-Me in com-
pound 4a is much less active than that of compound 1. By
optimizing conditions, the formylation of 4a was completed
at 40-50 °C within 2 hours and yielded 6a in 91% yield.
A number of methods have been developed for the
preparation of pyrrolo[2,1,5-cd]indolizines [1,5]. Over
recent years, the [8+2]-cycloaddition of indolizine with an
electron-deficient acetylene has been frequently employed
for this purpose. But it bears two significant drawbacks
arising from inaccessible electron-deficient acetylenes and
the requirment for 3-cyano- or 3-unsubstituted indolizines
without electron-withdrawing substitutents on C1 and C2
[6]. These drawbacks have seriously limited the range of
C1-C4 functionalized pyrrolo[2,1,5-cd]indolizines that
can be prepared by this method. So, there remains a need
for a more efficient and practical route for the synthesis of
pyrrolo[2,1,5-cd]indolizines. Herein we report an efficient
route that proceeds via preparation of 3-acyl-5-methylin-
dolizine followed by an intramolecular condensation and
overcomes some of the limitation of published procedures.
In our previous work, a general and convenient method
has been developed for the preparation of 3-unsubstituted
and 3-acylindolizines [7]. These results prompted us to
explore their further conversions into the corresponding
pyrrolo[2,1,5-cd]indolizines. By survey of literature, the
procedure for the preparation of pyrrolo[2,1,5-cd]-5-
azaindolizine (2) [8] draw our attention because its third
ring can be constructed in a single step from 5-methyl-6-
Intramolecular condensation of 3-acyl-5-methylin-
dolizine can be used for the preparation of pyrrolo-
[2,1,5-cd]indolizine. But this convenient method has almost
been ignored because it suffered seriously from very low
yields under several conditions [5h,8]. However, when 6a
was treated with potassium hydroxide in N,N-dimethyl-
formide at 160 °C for 10 minutes, the condensation occurred
and yielded the desired pyrrolo[2,1,5-cd]indolizine-1-car-
bonitrile (7a) in 94% yield (Scheme 2).

854
F. Liang, J. Hu, L. Zhang, Y. Hu and H. Hu
Vol. 38
8a-c
1
8, 6
X
R
R
Yield of 6 (%)
a, g
b, h
c, i
Br
Br
Cl
Br
Me
Ph
3,4-F C H
CN
CN
CN
91
99
56
82
2
6 3
b, j
Ph
CO Me
2
6g-j gave 3-substituted pyrrolo[2,1,5-cd]indolizines 7g-j
in 63-93% yields (Scheme 5).
To explore the scope of this novel route, 5-methylin-
dolizine-3-carboxaldehydes 6a-f and other 3-acyl-5-
methylindolizines 6g-j were tested. By known procedures,
3-unsubstituted 5-methylindolizines 4a-f, which are starting
materials for 6a-f, were prepared [5j][7c][11]. Compounds
4a-d were formylated with Vilsmeier reagent to give the
corresponding compounds 6a-d in 86-98% yields smoothly.
However, compound 4e was diformylated and yielded 2,5-
dimethylindolizine-1,3-dicarboxaldehyde (6e) in 95% yield
when two equivalents of phosphorus oxychloride was used.
Whereas compound 4f gave the 3-carboxaldehyde com-
pound 6f (67%) and 1-carboxaldehyde compound 6ff (32%)
when one equivalent of phosphorus oxychloride was used.
These results are in agreement with literature data on the
order of reaction activities of C1 and C3 on indolizine deriv-
atives [7b,8] (Scheme 3). As shown in Scheme 4, 3-acyl-5-
1
2
3
4
7
R
R
R
R
Yield of 7 (%)
a
b
c
d
e
f
g
h
i
CN
CN
COPh
COPh
CHO
H
CN
CN
CN
CO Me
H
H
H
Ph
Me
Ph
H
H
H
H
H
H
H
H
H
H
Me
H
H
H
H
H
H
H
H
94
99
98
95
83
91
89
92
93
63
Me
Ph
3,4-F C H
2 6 3
j
H
Ph
2
EXPERIMENTAL
All melting points were determined on a Yanaco melting point
apparatus and are uncorrected. The ir spectra were recorded on a
Nicolet FT-IR 5DX spectrometer with potassium bromide pellets.
1
The H nmr spectra were recorded on a Bruker ACF-300 spec-
1
2
3
4
4, 6
R
R
R
R
Yield of 6 (%)
trometer in chloroform-d with trimethylsilane as internal refer-
ence. The J values are given in Hz. The ms spectra were obtained
on a ZAB-HS mass spectrometer with 70 eV. The elemental
analyses were performed on a Perkin-Elmer 240C instrument. PE
is light petroleum (60-90 °C).
a, a
b, b
c, c
d, d
e, e
f, f
CN
CN
H
H
H
Ph
Me
Ph
Ph
H
Me
H
H
H
CHO
CHO
CHO
CHO
CHO
CHO
H
91
86
98
93
95
67
32
COPh
COPh
CHO(H for 4)
H
H
H
General Procedure for Preparation of 5-Methylindolizine-3-car-
boxaldehydes (6a-ff).
ff
CHO
To a stirred mixture of compound 4 (4 mmol) in N,N-dimethyl-
formamide (4 mL) was added dropwise Vilsmeier reagent (650 mg,
4.4 mmol of phosphorus oxychloride in 4 mL of N,N-dimethylfor-
mamide) at 40-50 °C. Two hours later, it was poured into ice-water.
Then 25% aqueous solution of sodium hydroxide (6 mL, 50 mmol)
was added and the mixture was refluxed for 15 minutes. After it was
cooled to room temperature, the solid was collected by filtration.
The crude product was purified by chromatography [silica gel, 20%
ethyl acetate in PE] to give pure product 6.
methylindolizines 6g-j were obtained conveniently by
oxidant promoted 1,3-dipolar cycloaddition between salts
8a-c (precursors of N-ylides) and electron-deficient alkenes,
acrylonitrile and methyl acrylate [7a].
Using the procedure reported for the preparation of 7a,
3-carboxaldehyde compounds 6b-f were converted to
3-unsubstituted pyrrolo[2,1,5-cd]indolizines 7b-f in high
yields. Under similar conditions, other 3-acyl derivatives

Jul-Aug 2001
Preparation of Pyrrolo[2,1,5-cd]indolizine Derivatives
855
Cyano-5-methylindolizine-3-carboxaldehyde (6a).
General Procedure for the Preparation of 3-Acyl-5-methylin-
dolizines (6g-j).
This compound was obtained as a white solid, mp 148-150 °C; ir:
-1
1
ν
2230, 1640 cm ; H nmr: δ 9.90 (1H, s, CHO), 7.92 (1H, s,
A mixture of 2-methylpyridine (9.3 g, 100 mmol) and the cor-
responding halide (100 mmol) in ethyl acetate (60 mL) was
stirred at room temperature for 4 hours. Crude salt 8 [8a, 87%,
mp 190-192 °C; 8b, 96%, mp 209-211 °C (Lit. [7a] 214 °C); 8c,
83%, mp 202-205 °C] was filtrated, rinsed with ethyl acetate and
dried in air. It was used for the next step without further purifica-
tion and characterization.
The mixture of 8 (10 mmol), alkene 9 (50 mmol), tetrakis-pyri-
dine cobalt (II) dichromate (4 g, 6.5 mmol) and sodium carbonate
(1.1 g, 10 mmol) in N,N-dimethylformamide (30 mL) was stirred
at 90-95 °C for 4-5 hours (monitored by tlc). The resultant mix-
ture was then cooled to room temperature and poured into 5%
hydrochloric acid. Crude solid 6 was filtrated and purified by
chromatography [20% ethyl acetate in PE].
max
ArH), 7.72 (1H, d, J = 8.7, ArH), 7.43 (1H, t, J = 7.9, ArH), 6.96
+
(1H, d, J = 7.0, ArH), 2.93 (3H, s, CH ); ms: m/z (%) 184 (M , 37),
3
167 (79), 155 (100), 129 (9), 128 (23), 127 (8), 101 (14), 77 (8).
Anal. Calcd. for C H N O: C, 71.73; H, 4.38; N, 15.21.
11
8 2
Found: C, 71.68; H, 4.42; N, 15.51.
1-Cyano-5,7-dimethylindolizine-3-carboxaldehyde (6b).
This compound was obtained as a white solid, mp 155-156 °C;
-1
1
ir: ν
2200, 1620 cm ; H nmr: δ 9.81 (1H, s, CHO), 7.88
max
(1H, s, ArH), 7.50 (1H, s, ArH), 6.82 (1H, s, ArH), 2.92 (3H, s,
CH ), 2.49 (3H, s, CH ); ms: m/z (%) 198 (M , 55), 197 (9), 182
+
3
3
(15), 181 (100), 169 (15), 166 (29), 77 (4).
Anal. Calcd. for C N O: C, 72.71; H, 5.09; N, 14.13.
H
12 10
2
Found: C, 72.75; H, 5.16; N, 14.22.
3-Acetyl-5-methylindolizine-1-carbonitrile (6g).
1-Benzoyl-5-methylindolizine-3-carboxaldehyde (6c).
This compound was obtained as a white solid, mp 134-135 °C;
This compound was obtained as a yellowish solid from salt 8a
-1
1
and had mp 145-146 °C; ir: ν
2200, 1640 cm ; H nmr: δ
max
-1
1
ir: ν
1640, 1630 cm ; H nmr: δ 9.91 (1H, s, CHO), 8.67
7.85 (1H, s, ArH), 7.72 (1H, d, J = 8.6, ArH), 7.44 (1H, t, J =
max
(1H, d, J = 8.7, ArH), 7.97 (1H, s, ArH), 7.90-7.84 (2H, m, 2 x
7.8, ArH), 6.95 (1H, d, J = 6.9, ArH), 2.67 (3H, s, COCH ), 2.64
3
+
ArH), 7.64-7.52 (4H, m, 4 x ArH), 7.04 (1H, d, J = 6.9, ArH),
(3H, s, CH ); ms: m/z (%) 198 (M , 64), 183 (100), 181 (46), 155
3
+
2.98 (3H, s, CH ); ms: m/z (%) 263 (M , 100), 262 (5), 246 (27),
(63), 129 (8), 77 (13), 43 (22).
3
234 (3), 186 (46), 105 (46), 77 (23).
Anal. Calcd. for C
H N O: C, 72.71; H, 5.09; N, 14.13.
12 10 2
Anal. Calcd. for C
H NO : C, 77.55; H, 4.98; N, 5.32.
Found: C, 72.60; H, 5.20; N, 14.13.
17 13 2
Found: C, 77.59; H, 4.91; N, 5.41.
3-Benzoyl-5-methylindolizine-1-carbonitrile (6h).
1-Benzoyl-2-phenyl-5-methylindolizine-3-carboxaldehyde (6d).
This compound was obtained as a yellowish solid from salt 8b
and had mp 160-161 °C (Lit. [7a] 160-162 C).
o
This compound was obtained as a yellowish solid, mp 123-124
°C (Lit. [9], 126 °C).
3-(3,4-Difluorobenzoyl)-5-methylindolizine-1-carbonitrile (6i).
2,5-Dimethylindolizine-1,3-dicarboxaldehyde (6e).
This compound was obtained as a yellow-green solid from salt
-1
1
8c and had mp 146-147 °C; ir: ν
2200, 1625 cm ; H nmr: δ
In this experiment, two equivalent of phosphorus oxychloride
max
7.91 (1H, d, J = 9.9, ArH), 7.86-7.78 (1H, m, ArH), 7.54 (1H, s,
ArH), 7.50 (1H, d, J = 8.6, ArH), 7.40-7.34 (2H, m, 2 x ArH),
was used. Compound 6e was obtained as a white solid, mp 173-
-1 1
174 °C; ir: ν
1660, 1630 cm ; H nmr: δ 10.25 (1H, s, CHO),
max
7.02 (1H, d, J = 6.9, ArH), 2.60 (3H, s, CH ); ms: m/z (%) 296
10.18 (1H, s, CHO), 8.48 (1H, d, J = 8.5, ArH), 7.54 (1H, t, J =
3
+
(M , 55), 295 (9), 279 (100), 183 (15), 155 (13), 141 (14), 113
7.9, ArH), 7.02 (1H, d, J = 7.1, ArH), 2.90 (3H, s, CH ), 2.88
3
+
(27), 77 (4).
(3H, s, CH ); ms: m/z (%) 201 (M , 100), 200 (21), 184 (19), 173
3
(26), 172 (18), 156 (72), 144 (46), 143 (15), 141(31), 77 (10).
Anal. Calcd. for C
H N OF : C, 68.92; H, 3.40; N, 9.46.
17 10 2 2
Anal. Calcd. for C
H NO : C, 71.63; H, 5.51; N, 6.96.
Found: C, 69.01; H, 3.57; N, 9.54.
12 11 2
Found: C, 71.63; H, 5.56; N, 6.86.
Methyl 3-Benzoyl-5-methylindolizine-1-carboxylate (6j).
This compound was obtained as a yellowish solid from salt 8b
2-Phenyl-5-methylindolizine-3-carboxaldehyde (6f).
This compound was obtained as a white solid, mp 70-71 °C; ir:
o
o
and had mp 117-118 C (Lit. [10], 115-116 C).
-1
1
ν
max
1620 cm ; H nmr: δ 9.42 (1H, s, CHO), 7.64-7.62 (2H, m,
General Procedure for Preparation of Pyrrolo[2,1,5-cd]-
indolizines (7a-j).
2 x ArH), 7.53-7.46 (4H, m, 4 x ArH), 7.37 (1H, t, J = 7.7, ArH),
6.89 (1H, d, J = 7.0, ArH), 6.74 (1H, s, ArH), 2.89 (3H, s, CH );
3
+
ms: m/z (%) 235 (M , 62), 234 (19), 218 (100), 206 (19), 77 (4).
To a mixture of potassium hydroxide (1.2 g, 20 mmol), toluene
(20 mL) and N,N-dimethylformamide (10 mL) at 160 °C was
added compound 6 (1 mmol) and the resultant mixture was
stirred for another 10 minutes. It was then cooled to room tem-
perature and poured into water. The mixture was extracted with
ethyl acetate and the combined organic layers were washed with
brine. After it was dried over sodium sulfate, the solvent was
removed to give a residue, which was purified by chromatogra-
phy [silica gel, 20% ethyl acetate in PE] to give pure product 7.
Anal. Calcd. for C
H NO: C, 81.68; H, 5.57; N, 5.95. Found:
16 13
C, 81.48; H, 5.72; N, 5.94.
2-Phenyl-5-methylindolizine-1-carboxaldehyde (6ff).
This compound was obtained as a white solid, mp 97-99 °C; ir:
-1
1
ν
1640 cm ; H nmr: δ 10.07 (1H, s, CHO), 8.44 (1H, d, J =
max
8.9, ArH), 7.65-7.40 (6H, m, 6 x ArH), 7.25 (1H, s, ArH), 6.79
+
(1H, d, J = 6.8, ArH), 2.65 (3H, s, CH ); ms: m/z (%) 235 (M ,
3
90), 234 (100), 218 (14), 206 (17), 205 (11), 204 (22), 191 (8),
178 (13), 77 (6).
Pyrrolo[2,1,5-cd]indolizine-1-carbonitrile (7a).
Anal. Calcd. for C
C, 81.63; H, 5.55; N, 5.93.
H
NO: C, 81.68; H, 5.57; N, 5.95. Found:
This compound was obtained as a yellow solid, mp 67-68 °C;
ir: νmax 2200 cm ; H nmr: δ 8.18 (1H, d, J = 7.9, ArH), 8.06
16 13
-1
1

856
F. Liang, J. Hu, L. Zhang, Y. Hu and H. Hu
Vol. 38
(1H, d, J = 7.7, ArH), 7.96-7.90 (2H, m, 2 x ArH), 7.71 (1H, d,
J = 4.7, ArH) , 7.49 (1H, d, J = 4.7, ArH); ms: m/z (%) 166 (M ,
Anal. Calcd. for C H N : C, 84.28; H, 4.16; N, 11.56.
17 10 2
Found: C, 84.27; H, 4.35; N, 11.43.
+
100), 165 (7), 139 (11).
3-(3,4-Difluorophenyl)pyrrolo[2,1,5-cd]indolizine-1-carbonitrile
(7i).
Anal. Calcd. for C H N : C, 79.50; H, 3.64; N, 16.86. Found:
11
6 2
C, 79.33; H 3.52; N, 16.75.
This compound was obtained as a yellow solid, mp 222-223
6-Methylpyrrolo[2,1,5-cd]indolizine-1-carbonitrile (7b).
This compound was obtained as a yellow solid, mp 87-88 °C;
-1
1
°C; ir: ν
2200 cm ; H nmr: δ 8.19 (1H, d, J = 7.8, ArH),
max
8.09 (1H, s, ArH), 8.04 (1H, d, J = 7.7, ArH), 7.96 (1H, t, J =
7.8, ArH), 7.81-7.72 (2H, m, 2 x ArH), 7.61 (1H, s, ArH), 7.37
(1H, d, J = 9.9, ArH); ms: m/z (%) 278 (M , 100), 277 (6), 258
-1
1
ir: νmax 2200 cm ; H nmr: δ 8.02 (1H, s, ArH), 7.87 (1H, s,
+
ArH), 7.84 (1H, s, ArH), 7.66 (1H, d, J = 4.7, ArH), 7.39 (1H, d,
+
(4), 252 (3), 250 (3), 139 (3).
J = 4.7, ArH), 2.86 (3H, s, CH ); ms: m/z (%) 180 (M , 100), 179
3
(99), 154 (2).
Anal. Calcd. for C H N F : C, 73.38; H, 2.90; N, 10.07.
17 8 2 2
Anal. Calcd. for C H N : C, 79.98; H, 4.48; N, 15.55. Found:
Found: C, 73.40; H, 3.13; N, 10.07.
12
8 2
C, 79.95; H, 4.54; N, 15.26.
Methyl 3-Phenylpyrrolo[2,1,5-cd]indolizine-1-carboxylate (7j).
This compound was obtained as a yellow solid, mp 109-110
1-Benzoylpyrrolo[2,1,5-cd]indolizine (7c).
This compound was obtained as a yellow solid, mp 88-89 °C;
-1
1
°C; ir: ν
1705 cm ; H nmr: δ 8.41-8.33 (2H, m, 2 x ArH),
max
-1
1
8.08-8.05 (2H, m, 2 x ArH), 7.95-7.86 (2H, m, 2 x ArH), 7.61
(1H, s, ArH), 7.58-7.53 (2H, m, 2 x ArH), 7.45 (1H, d, J = 7.2,
ir: νmax 1610 cm ; H nmr: δ 8.52 (1H, d, J = 7.7, ArH), 8.05-
7.93 (5H, m, 5 x ArH), 7.70 (1H, d, J = 4.7, ArH), 7.67-7.54 (3H,
+
+
ArH), 4.06 (3H, s, CH ); ms: m/z (%) 275 (M , 94), 244 (100),
m, 3 x ArH), 7.44 (1H, d, J = 4.7, ArH); ms: m/z (%) 245 (M ,
3
216 (33), 215 (32), 122 (15), 107 (8).
52), 168 (100), 140 (38), 77 (8).
Anal. Calcd. for C
Found: C, 78.56; H, 4.88; N, 5.12.
H NO : C, 78.53; H, 4.76; N, 5.09.
Anal. Calcd. for C H NO: C, 83.25; H, 4.52; N, 5.71. Found:
C, 83.36; H, 4.66; N, 5.68.
18 13 2
17 11
Acknowledgment.
1-Benzoyl-2-phenylpyrrolo[2,1,5-cd]indolizine (7d).
This compound was obtained as a yellow solid, mp 124-125 °C;
We are grateful to Natural Science Foundation of China for
financial support.
-1
1
ir: νmax 1620 cm ; H nmr: δ 8.11 (1H, d, J = 7.9, ArH), 8.01
(1H, d, J = 7.7, ArH), 7.88 (1H, t, J = 7.8, ArH), 7.78-7.75 (3H, m,
3 x ArH), 7.62-7.60 (2H, m, 2 x ArH), 7.47 (1H, d, J = 4.6, ArH),
7.40 (1H, d, J = 7.4, ArH), 7.31-7.26 (5H, m, 5 x ArH); ms: m/z
REFERENCES AND NOTES
+
(%) 321 (M , 0.42), 216 (48), 215 (100), 166 (10), 139 (2).
[1a] W. Flitsch and U. Kramer, in Adv. Heterocycl. Chem., Vol.
22, A. R. Katritzky and A. J. Boulton eds., Academic Press, New
York, 1978, p321; [b] W. Flitsch, Comprehensive Heterocyclic
Chemistry, Vol. 4, A. R. Katrizky and C. W. Rees eds., Pergmon
Press, 1984, p478; [c] Y. Tominaga, Y. Shiroshita and A. Hosomi,
Heterocycles, 27, 2251 (1988).
[2a] M. J. S. Dewar and N. Trinajstic, J. Chem. Soc. A, 1754
(1969); [b] K. Matsumoto, H. Katsura, J. Yamauchi, T. Uchida, K.
Aoyama and T. Machiguchi, Bull. Soc. Chim. Fr., 133, 891 (1996);
[c] C. W. Bird, Tetrahedron, 54, 10179 (1998).
Anal. Calcd. for C
H NO: C, 85.96; H, 4.70; N, 4.36. Found:
23 15
C, 86.01; H, 4.73; N, 4.15.
2-Methylpyrrolo[2,1,5-cd]indolizine-1-carboxaldehyde (7e).
This compound was obtained as a yellow solid, mp 102-103
-1
1
°C; ir: νmax 1640 cm ; H nmr: δ 10.38 (1H, s, CHO), 8.35 (1H,
d, J = 5.6, ArH), 7.94-7.89 (2H, m, 2 x ArH), 7.70 (1H, d, J =
4.7, ArH), 7.37 (1H, d, J = 4.7, ArH), 3.02 (3H, s, CH ); ms: m/z
3
+
(%) 183 (M , 94), 182 (100), 154 (25).
[3a] A. S. Jorgensen, P. Jacobsen, L. B. Christiansen, P. S.
Bury, A. Kanstrup, S. M. Thorpe, S. Bain, L. Nerum and K.
Wassermann, Bioorg. Med. Chem. Lett., 10, 399 (2000); [b] A. S.
Jorgensen, P. Jacobsen, L. B. Christiansen, P. S. Bury, A. Kanstrup, S.
M. Thorpe, S. Bain, L. Nerum and K. Wassermann, Bioorg. Med.
Chem. Lett., 10, 2383 (2000).
Anal. Calcd. for C H NO: C, 78.67; H, 4.95; N, 7.65; O, 8.73.
Found: C, 78.52; H, 4.88; N, 7.56.
12
9
2-Phenylpyrrolo[2,1,5-cd]indolizine (7f).
This compound was obtained as a yellow solid, mp 89-90 °C
(Lit. [11], 93.5-94.5 °C).
[4a] F. Schroder, V. Sinnwell, H. Baumann and M. Kaib, J.
Chem. Soc., Chem. Commun., 2139 (1996); [b] F. Schroder, S.
Franke, W. Francke, H. Baumann, M. Kaib and J. M. Pasteels,
Tetrahedron, 52, 13539 (1996); [c] F. Schroder, V. Sinnwell, H.
Baumann, M. Kaib and W. Francke, Angw. Chem. Int. Ed. Engl. 36,
77 (1997); [d] F. Schroder and W. Francke, Tetrahedron, 54, 5259
(1998); [e] G. V. Thanh, J. P. Celerier and G. Lhommet, Tetrahedron
Lett., 40, 3713 (1999); [f] B. Sayah, N. Pelloux-Leon and Y. Vallee,
J. Org. Chem., 65, 2824 (2000).
3-Methylpyrrolo[2,1,5-cd]indolizine-1-carbonitrile (7g).
This compound was obtained as a yellow solid, mp 75-76 °C;
-1
1
ir: νmax 2230, 1370 cm ; H nmr: δ 8.08 (1H, t, J = 4.3, ArH),
7.88-7.84 (3H, m, 3 x ArH), 7.19 (1H, s, ArH), 2.75 (3H, s, CH );
3
+
ms: m/z (%) 180 (M , 89), 179 (100), 178 (21), 177 (11), 154 (2).
Anal. Calcd. for C H N : C, 79.98; H, 4.48; N, 15.55. Found:
12
8 2
C, 79.77; H, 4.33; N, 15.29.
[5a] W. K. Gibson, D. Leaver, J. E. Roff, and C. W. Cumming,
J. Chem. Soc., Chem. Commun., 214 (1967); [b] W. H. Okamura and
T. J. Katz, Tetrahedron, 23, 2941 (1967); [c] W. Flitsch and R.
Heidhues, Chem. Ber. 101, 3843 (1968); [d] M. A. Jessep and D.
Leaver, J. Chem. Soc., Chem. Commun., 790 (1970); [e] R. M.
Acheson and J. Mck. Woollard, J. Chem. Soc. C, 3296 (1971); [f] D.
Johnson and G. Jones, J. Chem. Soc., Perkin Trans.1, 840 (1972); [g]
3-Phenylpyrrolo[2,1,5-cd]indolizine-1-carbonitrile (7h).
This compound was obtained as a yellow solid, mp 118-120
-1
1
°C; ir: ν
2200 cm ; H nmr: δ 8.17-8.12 (2H, m, 2 x ArH),
max
8.03-8.00 (3H, m, 3 x ArH), 7.94 (1H, t, J = 7.8, ArH), 7.68 (1H,
s, ArH), 7.60-7.55 (2H, m, 2 x ArH), 7.47 (1H, s, ArH); ms: m/z
+
(%) 242 (M , 100), 241 (8), 240 (17), 216 (6), 166 (4).

Jul-Aug 2001
Preparation of Pyrrolo[2,1,5-cd]indolizine Derivatives
857
E. Pohjala, Heterocycles, 2, 585 (1974); [h] K. Takada, J. Haginiwa
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2059 (1991); [c] H. Kojima and K. Yamamoto, J. Heterocyclic
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[e] Y. Matsuda, S. Kohra, K. Katou, T. Itou and T. Uemura,
Heterocyclics, 45, 2223 (1997); [f] J. O. Smith and B. K. Mandal, J.
Heterocyclic Chem., 34, 1441 (1997); [g] Y. Tominaga, K. Komiya,
S. Kataoka, Y. Shigemitsu, T. Hirota and K. Sasaki, Heterocyclics,
48, 1985 (1998); [h] Y. Tominaga, K. Sasaki and R. N. Castle, J.
Heterocyclic Chem., 35, 1219 (1998).
[7a] X. Wei, Y. Hu, T. Li and H. Hu, J. Chem. Soc., Perkin
Trans. 1, 2487 (1993); [b] B. Wang, X. Zhang, J. Li, X. Jiang, Y. Hu
and H. Hu, J. Chem. Soc., Perkin Trans. 1, 1571 (1999); [c] L.
Zhang, F. Liang, L. Sun, Y. Hu and H. Hu, Synthesis, 1733-1737
(2000).
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351 (1976).
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(1972).
[10] Y. Miki, Y. Hiroishi, H. Hachiken and S. Takemura, J.
Heterocyclic Chem., 28, 45 (1991).
[11] R. J. Windgassen, Jr., W. H. Saunders, Jr. and V.
Boekelheide, J. Am. Chem. Soc., 81, 1459 (1959).