Synthesis of condensed heterocycles via cyclopropylimine rearrangement of cyclopropylazoles

Article abstract of DOI:10.1016/j.tetlet.2010.07.096

Thermal cyclopropylimine rearrangement of cyclopropylazoles into condensed heterocycles and factors affecting the regioselectivity and conversion are reported. A method of conducting the reaction in the absence of solvents is developed. A series of 2-cyclopropylazoles, including novel examples, is synthesized and their transformations into the corresponding condensed heterocyclic compounds (2,3-dihydro-1H-pyrroles and 6,7-dihydro-5H-pyrrolo[2,1- b]thiazolium salts) are studied.

Full text of DOI:10.1016/j.tetlet.2010.07.096

Tetrahedron Letters 51 (2010) 5120–5123
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Tetrahedron Letters
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Synthesis of condensed heterocycles via cyclopropylimine rearrangement
of cyclopropylazoles
*
Yury V. Tomilov , Dmitry N. Platonov, Aleksandr E. Frumkin, Dmitry L. Lipilin, Rinat F. Salikov
N.D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, 47 Leninsky prospect, 119991 Moscow, Russian Federation
a r t i c l e i n f o
a b s t r a c t
Article history:
Thermal cyclopropylimine rearrangement of cyclopropylazoles into condensed heterocycles and factors
affecting the regioselectivity and conversion are reported. A method of conducting the reaction in the
absence of solvents is developed. A series of 2-cyclopropylazoles, including novel examples, is synthe-
sized and their transformations into the corresponding condensed heterocyclic compounds (2,3-dihy-
dro-1H-pyrroles and 6,7-dihydro-5H-pyrrolo[2,1-b]thiazolium salts) are studied.
Received 23 April 2010
Revised 25 June 2010
Accepted 16 July 2010
Available online 22 July 2010
Ó 2010 Elsevier Ltd. All rights reserved.
Keywords:
Cyclopropylazoles
Cyclopropylimine rearrangement
2-Cyclopropylbenzimidazole
2,3-Dihydro-1H-benzo[d]pyrrolo[1,2-
a]imidazole
2-Cyclopropylbenzothiazole
2,3-Dihydro-1H-benzo[d]pyrrolo[2,1-
b]thiazol-9-ium bromide
Antitumor activity
Green chemistry
It has been reported1 that protonated C-cyclopropylimines and
the related compounds undergo thermal rearrangement to form
five-membered azaheterocyclic compounds. General methods for
the synthesis of various alkaloids based on this reaction,2–7 and a
possible mechanism, have been proposed.2,8,9 The suggested mech-
anism involves protonation of the imine nitrogen atom, nucleophilic
attack of the counterion forming a ring-opened product, and intra-
molecular alkylation with ring closure. In some cases the rearrange-
ment can also proceed via a different mechanism without the need
for a nucleophilic counterion.9–12 To date, the rearrangement
(Scheme 1) has been studied in detail for acyclic derivatives of cyclo-
propylimines2,8,9 and cyclopropylthiomethylimidates13,14 only. To
the best of our knowledge, only one example of the rearrangement
of a heterocyclic compound has been reported.15
The factors affecting the regioselectivity and conversion were
studied systematically for 2-cyclopropyl-1H-benzimidazole (1).17
The reactions were carried out by heating hydrohalogenides 1a–c
in various solvents or without any solvent; neutral benzimidazoles
1 as well as mixtures with ammonium halides were used (Scheme
3, Table 1).18 The conversion of compounds 1 into the previously
described 2,3-dihydro-1H-benzo[d]pyrrolo[1,2-a]imidazole salts19
was evident from 1H NMR spectra.
It was found that the reaction rate increases in the transition
from hydrochlorides to hydroiodides in all cases. Therefore, the
use of iodides is attractive even though they are less readily avail-
able. The conversion depends essentially on the temperature and
the solvent. For instance, the conversion of highly reactive hydroio-
dide 1c in xylene (140 °C, 2.5 h) was just 6% while hydrochloride
1a, in decalin at 190 °C, rearranged almost completely in the same
We found that
a-cyclopropyl-substituted azole hydrohaloge-
nides which contain a cyclopropyliminium fragment undergo
ring-opening rearrangement to form condensed pyrrolinium ha-
lides or pyrrolines depending on the nature of the starting azole
(Scheme 2). This reaction is quite general and some of the hetero-
cyclic compounds obtained are useful synthons for the preparation
of both new and known biologically active compounds. For exam-
ple, pyrrolo[1,2-a]imidazoles containing a condensed benzoqui-
none fragment exhibit pronounced antitumor activity.16
N R
Y
HX, Δ
N
R
Y
R = H, Alkyl;Y = H, Alkyl, SAlkyl
S
S
200 °C
N
H2N
N .
HBr
H2N
Br
* Corresponding author. Tel./fax: +7 499 135 63 90.
E-mail address: tom@ioc.ac.ru (Y.V. Tomilov).
Scheme 1.
0040-4039/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2010.07.096

Y. V. Tomilov et al. / Tetrahedron Letters 51 (2010) 5120–5123
5121
We have further studied this rearrangement with a series of
substituted cyclopropylbenzimidazoles 4a–d. The starting 5-meth-
oxy- and 5-methyl-2-cyclopropyl-1H-benzimidazoles 4a20 and
4b21 were obtained by reaction of the corresponding phenylenedi-
amines with cyclopropanecarboxylic acid iminoester, in yields of
65% and 70%, respectively. 5-Nitro-2-cyclopropylbenzimidazole
(4c) was synthesized according to a known procedure.22 2-Cyclo-
propyl-5,6-dinitro-1H-benzimidazole (4d) was prepared by nitra-
tion of 1 with a mixture of nitric and sulfuric acids in a yield of
87%.23
S
N
N
Y
Y
N
X
HX
Y = S
N
H
Y = NH
N
X
X = Cl, Br, I
Scheme 2.
In order to transform cyclopropylbenzimidazoles 4a–d into 2,3-
dihydro-1H-benzo[d]pyrrolo[1,2-a]imidazoles 5 and 6, we chose a
method24 which involved melting a mixture of 4 with ammonium
iodide at 150 °C with no solvent, (Scheme 4, Table 2), since com-
pounds 4c and 4d contain electron-withdrawing groups making
them less basic and unable to form hydrohalogenides.
N
N
N
6
7
3
N
HX
H
1
1a–c
2
Δ
B–
N
Electron-withdrawing groups, such as the nitro group, decrease
the reaction time while electron-donating groups, such as methyl
or methoxy, essentially increase the time. For instance, the conver-
sion of 4a (melt with ammonium iodide) after 1 h was 28% while
4c was converted quantitatively. Thus, the more positive the charge
on the reaction center, the easier the rearrangement proceeds.
In the case of asymmetrically substituted benzimidazoles 4a–c
the reaction leads to a mixture of two isomers. There is a small
prevalence of isomers 5a,b containing the donating groups, while
the formation of 6c is preferred in the case of the nitro derivative.
This can be explained by the difference in the electronic effects of
the substituents on the nitrogen atoms of the imidazole ring. In the
case of compounds 4a,b, cyclization mainly occurs at the nitrogen
atom which is para relative to the donating groups, and for the ni-
tro derivative, at the meta position. Identification of the isomers
was based on the spin constants in the 1H NMR spectra and on
NOESY experiments.
N
HX
N
N
H
3a–c
HX
2a–c
X = Cl (a), Br (b), I (c)
Scheme 3.
Table 1
Conversions of 2-cyclopropyl-1H-benzimidazoles 1 into compounds 2 under various
conditions18
Solvent
T (°C)
Time (min)
Conversiona of 1 (%)
1a
1b
1c
Xyleneb
140
150
190
150
150
200
200
150
150
150
60
60
10
—
0
—
6
Decalinc
5
—
100
80
65
100
100
Decalinc
96
25
5
55
15
100
65
20
95
100
In most cases when describing the transformations of cyclopro-
pylimine derivatives into pyrrolines, reports do not draw analogy
with the vinylcyclopropane–cyclopentene rearrangement25 and
the process is considered as bimolecular.
Cyclohexanonec
DMFb
No solvent
No solventd
10
We have found that in the presence of effective electron-with-
drawing groups, as with the dinitro derivative 4d, the rearrange-
ment can proceed without the need for a nucleophilic counterion
by simply melting the starting material (ꢀ200 °C). Apparently, the
presence of the electron-withdrawing groups creates a sufficient po-
sitive charge at the reaction center, and the intermediate in this case
is neutral, as in the case of the vinylcyclopropane–cyclopentene and
azocyclopropane–pyrazoline rearrangements. However, the yield of
the desired product 5d was lower (40%) than, for example, in the
case of melting the reagent with ammonium iodide (Table 2), where
the degree of side transformations was extremely low.
a
Conversion determined by 1H NMR spectroscopy. The reaction gives only one
product, hence its yield is presumed to be equal to the conversion.
b
The residue was analyzed after solvent removal by evaporation.
The residue was analyzed after an aqueous extraction and evaporation of the
c
water phase.
d
Thermolysis of 1 was carried out in the presence of 1.2 equiv of NH4X [X = Cl (a),
Br (b), I (c)].
amount of time. Polar solvents accelerate the rearrangement, for
example, the conversion of hydrobromide 1b in decalin (150 °C,
2.5 h) was about 5%, but in cyclohexanone (150 °C, 1 h) the conver-
sion reached 65% in 60 min.
Further, we have synthesized and studied the transformations
of other cyclopropylazoles, in particular 2-cyclopropylbenzothiaz-
ole 7 and 2-cyclopropylbenzoxazole 8 hydrobromides. The benzox-
azole 8 was synthesized according to a known procedure,26 and
compound 7 was prepared from 2-aminothiophenol and cyclopro-
panecarboxylic acid chloride in a yield of 70%. It should be noted
that the cyclization of thioamide 9 proceeds in the presence of
PPA at 180 °C. In spite of these harsh conditions the 2-cyclo-
propylbenzothiazole does not rearrange, whereas the transforma-
tion of hydrobromide 7 was complete in less than 30 min as a
melt at 150 °C,27 to give the previously described 2,3-dihydro-
1H-benzo[d]pyrrolo[2,1-b]thiazol-9-ium bromide (10)28 in a yield
of 72% (Scheme 5). Thus, hydrobromide 7 is more reactive than
2-cyclopropylbenzimidazole hydrobromide 1b, which rearranges
under these conditions only by 5%.
It should be noted that the reaction can be carried out with
melted salts without any evident loss of yield and with a decrease
in reaction time. For example, hydrobromide 1 completely rear-
ranged at 200 °C in just 10 min. The only limiting factor in this case
is the melting point of the hydrohalogenide since the reaction pro-
ceeds only in a melt. This can be considered a green process. Imi-
nocyclopropane–pyrroline rearrangement can be carried out by
melting the starting benzimidazole 1 with ammonium halogenides
(Table 1). This method is useful for the rearrangement of azoles
which do not form hydrohalogenides due to their low basicity.
The salts 2a–c can be easily transformed into the free base 2 upon
treatment with aqueous alkali followed by extraction with ethyl
acetate.
An important feature of the iminocyclopropane–pyrroline rear-
rangement is the restoration of the heteroaromatic imidazole ring,
thus the anticipated intermediate 3 easily transforms into the
more stable structure 2.
In contrast to benzothiazole 7, the rearrangement of benzoxaz-
ole 8 proceeds differently. Instead of the expected condensed het-
erocycle 11 the only reaction product was pyrrolidin-2-one 12,

5122
Y. V. Tomilov et al. / Tetrahedron Letters 51 (2010) 5120–5123
R1
R1
R2
N
R1
R2
N
°
NH4I, 150 C
N
+
R2
N
N
H
N
4a-d
R1 = Me, MeO, NO2; R2 = H, NO2
5a-d
6a-c
Scheme 4.
Table 2
method is useful for the synthesis of benzopyrroloimidazoles and
benzopyrrolothiazolium salts.
Cyclopropylimine rearrangement of substituted 2-cyclopropyl-1H-benzimidazoles
4a–d into compounds 5a–d and 6a–c in the presence of ammonium iodide at 150 °C24
Compound
R1
R2
Time (h)
Yield (%)
Ratio 5:6a
Acknowledgments
4a
4b
4c
4d
MeO
Me
NO2
NO2
H
H
H
NO2
6
76
55
58
83
60:40
56:44
45:55
—
2.5
0.7
1
This work was supported financially by the Presidium of the
Russian Academy of Sciences (Program for Basic Research ‘Elabora-
tion of Methods for the Synthesis of Chemical Substances and Cre-
ation of New Materials’) and the Division of Chemistry and
Materials Science of the Russian Academy of Sciences (Program
for Basic Research ‘Biomolecular and Medical Chemistry’).
a
The ratio was determined from the NMR spectra of the reaction mixtures and
did not change considerably after purification.
Supplementary data
H
N
NH2
COCl
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.tetlet.2010.07.096.
NEt3, MeCN, 0 o
C
O
SH
SH
9
References and notes
1) PPA, 180 oC
2) HBr/MeOH
1. Cloke, J. B. J. Am. Chem. Soc. 1929, 51, 1174–1187.
2. Stevens, R. V. Acc. Chem. Res. 1977, 10, 193–198.
3. Heidt, P. C.; Bergmeier, S. C.; Pearson, W. H. Tetrahedron Lett. 1990, 31, 5441–
5444.
4. Pearson, W. H.; Bergmeier, S. C.; Williams, J. P. J. Org. Chem. 1992, 57, 3977–
3987.
5. Howell, A. R.; Martin, W. R.; Sloan, J. W.; Smith, W. T., Jr. J. Heterocycl. Chem.
1991, 28, 1147–1151.
6. Rawal, V. H.; Michoud, C.; Monestel, R. J. Am. Chem. Soc. 1993, 115, 3030–3031.
7. Boeckman, R. K., Jr.; Breining, S. R.; Arvanitis, A. Tetrahedron 1997, 53, 8941–
8962.
· HBr
N
150 o
C
N
S
Br
S
10
7
Scheme 5.
8. Boeckman, R. K., Jr.; Jackson, P. F.; Sabatucci, J. P. J. Am. Chem. Soc. 1985, 107,
2191–2192.
9. Soldevilla, A.; Sampedro, D. Org. Prep. Proced. Int. 2007, 39, 563–590. and
references cited therein.
10. Wasserman, H. H.; Dion, R. P. Tetrahedron Lett. 1983, 24, 3409–3412.
11. Wu, P.-L.; Wang, W.-S. J. Org. Chem. 1994, 59, 622–627.
12. Kagabu, S.; Tsuji, H.; Ozeki, H. Bull. Chem. Soc. Jpn. 1995, 68, 341–349.
13. Kuduk, S. D.; Ng, C.; Chang, R. K.; Bock, M. G. Tetrahedron Lett. 2003, 44, 1437–
1440.
· HBr
N
150 o
C
N
O
Br
O
8
11
150 o
C
14. Chang, R. K.; DiPadro, R. M.; Kuduk, S. D. Tetrahedron Lett. 2005, 46, 8513–8516.
15. Samet, A. B.; Firgang, S. I.; Semenov, V. V. Chem. Heterocycl. Compd. 2005, 6,
914–926.
N
N
O
Br
16. Skibo, E. B. U.S. Patent 6,998,413, 2006; Chem. Abstr. 2006, 133, 12985.
17. Elderfield, R. C.; McCarthy, J. R. J. Am. Chem. Soc. 1951, 73, 975–984.
18. The rearrangement of 2-cyclopropylbenzimidazole (1) into 2,3-dihydro-1H-
benzo[d]pyrrolo[1,2-a]imidazole (2): hydrohalogenide 1a–c (0.5 mmol), either
in 2 ml of solvent or without any solvent in a melt, as well as a mixture of
neutral benzimidazole with an ammonium halide (0.6 mmol), was heated at
the temperature and for the time indicated in Table 1. After cooling to room
temperature the solvent (xylene or DMF) was removed in vacuo, or in other
cases, the mixture was initially treated with H2O and the aqueous phase
evaporated in vacuum. The residue was analyzed by 1H NMR spectroscopy
(CDCl3) to determine the conversion (see Table 1).
OH
OH
12
Scheme 6.
which was identified by comparing its 1H NMR spectrum with that
previously described.26 The reaction was carried out by heating
hydrobromide 8 for 30 min at 150 °C. Despite preliminary drying
of the starting hydrobromide under vacuum and carrying out the
reaction under an inert atmosphere, the sample probably con-
tained sufficient water for the formation of compound 12 which
can form via two different pathways. Oxazole ring-opening can
take place after rearrangement of compound 8 into compound
11. On the other hand, the unstable oxazole can undergo ring-
opening first followed by rearrangement of the resulting bromocy-
clopropylimine and hydrolysis (Scheme 6).
19. Allin, S. M.; Bowman, W. R.; Karim, R.; Rahman, S. S. Tetrahedron 2006, 62,
4306–4316.
20. 2-Cyclopropyl-5-methoxy-1H-benzimidazole (4a): cyclopropanecarboximidic
acid ethyl ester hydrobromide (3.00 g, 20.0 mmol) was added to a solution of
4-methoxybenzene-1,2-diamine (2.76 g, 20.0 mmol) in absolute EtOH (30 ml),
and the mixture was heated to reflux for 1 h. The solution was cooled to room
temperature and 3% aqueous NH3 (30 ml) was added. The resulting emulsion
was extracted with EtOAc (2 Â 30 ml). The combined organic layer was dried
over anhydrous MgSO4 and the solvent was removed in vacuo.
Chromatographic purification on silica gel (CHCl3–EtOAc 1:1) afforded 4a:
65% yield, orange oil; EI-MS, m/z: 188 (M+, 80), 187 (M+ÀH, 100), 173 (85), 143
(32). Anal. Calcd for C11H12N2O: C, 70.19; H, 6.43; N, 14.88. Found: C, 70.23; H,
6.39; N, 14.65. 1H NMR (300 MHz, DMSO-d6) d 0.96–1.07 (m, 4H, 2CH2), 2.01–
2.12 (m, 1H, CH), 3.76 (s, 3H, OCH3), 6.71 (dd, 3J = 8.8, 4J = 2.6 Hz, 1H, H-6), 6.94
In conclusion, a simple and environmentally friendly method
for the synthesis of condensed azoles has been developed. This

Y. V. Tomilov et al. / Tetrahedron Letters 51 (2010) 5120–5123
5123
(d, 4J = 2.6 Hz, 1H, H-4), 7.28 (d, 3J = 8.8 Hz, 1H, H-7), 12.00 (s, 1H, NH); 13C
NMR (75 MHz, DMSO-d6) d 7.4 (2CH2) 8.6 (CH), 54.8 (OCH3), 97.0 (C-4), 109.1
(C-6), 113.7 (C-7), 132.9 (C-3a), 138.4 (C-7a), 154.5 (C-5), 155.9 (C-2).
21. Yang, D.; Fu, H.; Hu, L.; Jiang, Y.; Zhao, Y. J. Org. Chem. 2008, 73, 7841–7844.
22. Haugwitz, D. R.; Narayanan, L. V. DE 2328095, 1973; Chem. Abstr. 1973, 80,
82973.
23. 2-Cyclopropyl-5,6-dinitro-1H-benzimidazole (4d): 2-cyclopropyl-1H-benzimid
azole 1 (1.00 g, 5.0 mmol) was added to a mixture of 57% HNO3 (2 ml) and
concentrated H2SO4 (10 ml) at 10–15 °C and the mixture was stirred for 1 h
and then heated to 70–80 °C and treated with further 57% HNO3 (2 ml). The
mixture was stirred for 30 min, cooled to room temperature, and poured into
ice water (100 ml). The resulting precipitate was filtered and dried in air to give
zoles (6a) (60:40): light-brown crystals; IR (KBr):
m
2928, 2832, 1628, 1484; EI-
MS, m/z: 188 (M+, 67), 173 (M+ÀCH3, 100), 145 (26); 1H NMR (300 MHz, DMSO-
d6) d 2.64–2.74 (m, both isomers, 4H, CH2), 2.98 (t, 3J = 6.6 Hz, 1.6H, CH2 for 6a),
3.01 (t, 3J = 7.1 Hz, 2.4H, CH2 for 5a), 3.85 (s, 2.4H, OCH3 for 5a), 3.87 (s, 3.6H,
OCH3 for 6a), 4.13 (t, 3J = 7.0 Hz, 1.6H, NCH2 for 6a), 4.14 (t, 3J = 6.9 Hz, 2.4H,
NCH2 for 5a), 6.85–6.90 (dd, 3J = 8.7, 4J = 2.4 Hz, 2H, both isomers), 7.10 (d,
4J = 2.4 Hz, 0.8H, for 6a), 7.17 (d, 4J = 2.4 Hz, 1.2H, for 5a), 7.42 (d, J = 8.7 Hz, 1.2H,
for 5a), 7.49 (d, J = 8.7 Hz, 0.8H, for 6a); 13C NMR (75 MHz, DMSO-d6) d for 5a:
22.6 (C-2), 25.1 (C-3), 42.1 (C-1), 54.9 (OCH3), 101.3 (C-5), 109.5 (C-7), 109.8 (C-
8), 126.3 (C-8a), 148.5 (C-4a), 154.5 (C-6), 160.9 (C@N); for 6a: 22.3 (C-2), 25.2
(C-3), 41.8 (C-1), 55.0 (OCH3), 93.5 (C-8), 109.7 (C-6), 118.3 (C-5), 132.2 (C-8a),
141.9 (C-4a), 154.6 (C-6), 159.6 (C@N).
4d: 87% yield; light yellow crystals; IR (KBr):
m
3604, 3044, 2928, 1632, 1544,
6,7-Dinitro-2,3-dihydro-1H-benzo[d]pyrrolo[1,2-a]imidazole (5d): light yellow
820; EI-MS, m/z: 248 (M+, 90), 156 (M+À2NO2, 100), 130 (25). Anal. Calcd for
crystals, mp 256–258 °C; IR (KBr): m 3768, 3028, 2956, 1620, 1544, 1528; EI-
C
10H8N4O4: C, 48.39; H, 3.25; N, 22.57. Found: C, 48.23; H, 3.30; N, 22.65. 1H
MS, m/z: 248 (M+, 100), 218 (16), 172 (6). Anal. Calcd for C10H8N4O4: C, 48.39; H,
3.25; N, 22.57. Found: C, 48.50; H, 3.37; N, 22.44. 1H NMR (200 MHz, DMSO-d6) d
2.69 (quin, 3J = 7.5 Hz, 2H, CH2), 3.10 (t, 3J = 7.5 Hz, 2H, CH2), 4.28 (t, 3J = 7.5 Hz,
2H, NCH2), 8.37 (s, 1H), 8.51 (s, 1H); 13C NMR (75 MHz, DMSO-d6) d 23.0 (C-2),
25.1 (C-3), 43.6 (C-1), 108.7 and 115.5 (C-5, C-8), 132.6 and 136.7 (C-6, C-7),
137.5 (C-4a), 148.3 (C-8a), 168.8 (C@N).
NMR (200 MHz, DMSO-d6) d 1.14–1.34 (m, 4H, 2CH2), 2.23–2.38 (m, 1H, CH),
8.31 (s, 2H, 2CH), 9.43 (s, 1H, NH); 13C NMR (75 MHz, DMSO-d6) d 9.1 (CH) 10.3
(2CH2), 111.4 (2CH), 137.7 and 138.0 (2 Â 2C), 164.8 (C@N).
24. General procedure for the rearrangement of substituted 2-cyclopropylbenzimida
zoles (4a–d) into substituted 2,3-dihydro-1H-benzo[d]pyrrolo[1,2-a]imidazoles (5
and 6): compound 4a–d (5.3 mmol) was ground with NH4I (6.4 mmol) and then
heated at 150 °C for the time indicated in Table 2. After cooling to room
temperature, the mixture was treated with a solution of NaOH (16 mmol) in H2O
(20 ml) in the case of compounds 4a,b, or the mixture was treated with H2O
(20 ml) in the case of nitrocompounds 4c,d, and the aqueous phase was
extracted with EtOAc (2 Â 20 ml). The combined organic layer was dried over
anhydrous MgSO4 and the solvent was removed in vacuo. The residue was
25. Hudlicky, T.; Kutchan, T. M.; Naqvi, S. M. Org. React. 1987, 33, 247–335.
26. Yang, Y. H.; Shi, M. Tetrahedron 2006, 62, 2420–2427.
27. 2,3-Dihydro-1H-benzo[d]pyrrolo[2,1-b]thiazol-9-ylium bromide (10): concentrated
hydrobromic acid (3.7 ml) was added to a suspension of 2-cyclopropylben
zothiazole (5.40 g, 31 mmol) in a mixture of H2O (20 ml) and MeOH (10 ml). The
mixture was stirred for 1 h and evaporated. Theresidue (compound 7) was heated
at 150 °C for 30 min and allowed to cool to room temperature. The mixture was
dissolved in 2-propanol (50 ml), filtered, concentrated, and crystallized from 2-
propanol to give the known28 product 10 in 72% yield.
crystallized from
regioisomeric mixture of 5a–c and 6a–c or pure compound 5d (see Table 2).
6-Methoxy- (5a) and 7-methoxy-2,3-dihydro-1H-benzo[d]pyrrolo[1,2-a]imida
a mixture of toluene and acetonitrile (9:1) to give a
28. Babichev, F. S.; Neplyuev, V. M. J. Gen. Chem. USSR 1962, 32, 853–857.