New strategy for the synthesis of N-aryl pyrroles: Cu-catalyzed C-N cross-coupling reaction of trans-4-hydroxy-l-proline with aryl halides

Article abstract of DOI:10.1016/j.tetlet.2010.12.016

trans-4-Hydroxy-l-proline is used for the first time as an effective nucleophilic coupling partner with aryl halides mediated by copper iodide with Cs₂CO₃ as the base and DMSO as the solvent. Utilizing this protocol cross-coupling of trans-4-hydroxy-l-proline with a wide variety of substituted aryl halides to produce N-aryl pyrroles in moderate to good yields.

Full text of DOI:10.1016/j.tetlet.2010.12.016

Tetrahedron Letters 52 (2011) 777–780
Contents lists available at ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
New strategy for the synthesis of N-aryl pyrroles: Cu-catalyzed C–N
cross-coupling reaction of trans-4-hydroxy-L-proline with aryl halides
⇑
V. Prakash Reddy, A. Vijay Kumar, K. Rama Rao
Organic Chemistry Division-I, Indian Institute of Chemical Technology, Hyderabad 500 607, India
a r t i c l e i n f o
a b s t r a c t
Article history:
trans-4-Hydroxy-
halides mediated by copper iodide with Cs2CO3 as the base and DMSO as the solvent. Utilizing this pro-
tocol cross-coupling of trans-4-hydroxy- -proline with a wide variety of substituted aryl halides to pro-
duce N-aryl pyrroles in moderate to good yields.
L-proline is used for the first time as an effective nucleophilic coupling partner with aryl
Received 21 September 2010
Revised 2 December 2010
Accepted 4 December 2010
Available online 9 December 2010
L
Ó 2010 Elsevier Ltd. All rights reserved.
Keywords:
Aryl halides
trans-4-Hydroxy-
N-Aryl pyrroles
Cross-coupling
Copper iodide
L-proline
Pyrroles are an important class of organic compounds found in
many natural products and bioactive molecules.1 These com-
pounds exhibit remarkable activities such as antitumor, immuno-
suppressant, anti HIV, anti inflammatory, antioxidant etc.2 They
have also been widely used in material science and molecular rec-
ognition studies.3
tions,11 we report, herein, a new approach for the synthesis of N-
aryl pyrroles via C–N cross coupling of trans-4-hydroxy- -proline
with aryl halides catalyzed by CuI/Cs2CO3/DMSO at 110 °C for
24 h via an one-pot procedure (Scheme 1). To the best of our
knowledge, this is the first protocol explored for the synthesis of
L
N-aryl pyrroles via C–N cross-coupling of trans-4-hydroxy-L-pro-
In view of their significance, several useful strategies have been
developed for construction of the pyrrole moiety.4–6 Conventional,
protocols for their preparation include the cyclocondensation of
primary amines with 1,4-dicarbonyl compounds5 (Pall–Knorr reac-
tion) or 2,5-dimethoxy tetrahydrofuran7 and transition metal cat-
alyzed coupling of aryl halides with pyrroles.8 Despite these huge
developments, the transition metal catalyzed cross-coupling reac-
tion is considered to be the most attractive method for the synthe-
sis of pyrroles. Recently Che and co-workers reported ligand-free
CuCl-catalyzed C–N bond formation in 40% nBu4N+OHÀ aqueous
solution.9 In these reactions, the coupling between pyrroles and
aryl halides is commonly involved. Since pyrrole is not a biomass
line with aryl halides.
Initially the reaction between trans-4-hydroxy-L-proline with
iodo benzene was selected as a model reaction for optimizing the
reaction conditions, such as various copper sources, bases, sol-
vents, and temperature (Table 1). First, several copper catalysts
were screened (Table 1, entries 1 and 10–14), and CuI was proven
to be preeminent for this tandem reaction (Table 1, entry 5).
Among various bases screened, KOH and Cs2CO3 provided the N-
aryl pyrrole in moderate to excellent yields (Table 1, entries 3
and 5). Other bases such as NaOMe and K3PO4 gave lesser amount
of the desired product (Table 1, entries 4 and 6). Among the sol-
vents, DMSO yielded the best results whereas PEG gave the prod-
ucts in moderate yields (Table 1, entry 8) while solvents like
toluene, water, and DMF were ineffective (Table 1, entries, 6, 7,
and 9). The coupling reaction did not occur in the absence of cata-
lyst (Table 1, entry 15) as well as the base (Table 1, entry 16). When
resource, we have explored trans-4-hydroxy-L-proline (obtained
from collagen10) as a sustainable replacement of pyrrole for syn-
thesizing N-arylpyrroles.
Our recent report on b-CD catalyzed synthesis of pyrrole-substi-
tuted indolinones by using trans-4-hydroxy-
us to attempt trans-4-hydroxy- -proline as a nucleophilic coupling
L
-proline6c prompted
L
partner in Cu catalyzed C–N cross-coupling reaction. In the course
of our continuing investigations in the field of cross-coupling reac-
HO
CuI (20 mol%)
Cs2CO3 (2.5 equiv)
DMSO (3.0 mL)
O
I
N
R
R
N
H
OH
⇑
Corresponding author. Tel.: +91 40 27193164; fax: +91 40 27160512.
E-mail address: kakulapatirama@gmail.com (K.R. Rao).
Scheme 1. CuI catalyzed synthesis of N-aryl pyrroles.
0040-4039/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2010.12.016

778
V. P. Reddy et al. / Tetrahedron Letters 52 (2011) 777–780
Table 1
failed (Table 3, entry 3). The reactivity of the iodo benzene moiety
was confirmed by the chemoselective results obtained from the
benzene substituted with mixed halides. The cross-coupling
Screening of copper-catalyzed cross-coupling of aryl iodide with trans-4-hydroxy-L-
prolinea
Entry
Catalyst
Solvent
Base
T (°C)
Yieldb (%)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuI
DMSO
DMSO
DMSO
DMSO
DMSO
Toluene
H2O
KOH
KOH
KOH
rt
80
0
20
46
10
94
10
Trace
60
20
73
75
85
69
81
0c
Table 3
N-Aryl pyrroles synthesis from various aryl iodidesa
110
110
110
110
110
110
110
110
110
110
110
110
110
110
NaOMe
Cs2CO3
K3PO4
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
—
HO
CuI, DMSO, Cs2CO3
O
I
Ar
N
Ar
24 h, 110 0
C
N
H
OH
PEG
DMF
Entry
Aryl halide
Product
Yieldb (%)
CuI
CuO
Cu2O
CuCl2Á2H2O
CuSO4Á5H2O
Cu(OAc)2ÁH2O
—
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
94
93c
I
N
1
2
N
86
0
I
CuI
0d
I
N
3
a
Reaction conditions: iodobenzene (1.0 mmol), trans-4-hydroxy-L-proline
(2.0 mmol), catalyst (20 mol %), base (2.5 equiv), solvent (3.0 mL), 24 h.
b
Isolated yield.
In the absence of catalyst.
In the absence of base.
I
N
4
5
6
89
84
92
c
d
I
I
N
N
MeO
MeO
MeO
the reaction was conducted at room temperature and at 80 °C, the
yields observed were very low (Table 1, entries 1 and 2). The ideal
temperature for the reaction was found to be 110 °C.
We have also made a study of C–N cross coupling with various
electrophiles under these conditions. Among these electrophiles
iodo benzene yielded the best results whereas other electrophiles
were ineffective (Table 2).
N
I
7
89
MeO
N
OMe
O
I
8
9
70
89
OMe
Ph
O
Ph
To explore the scope of this novel transformation, we examined
the cross-coupling of various substituted iodo benzenes with trans-
I
N
4-hydroxy-L
-proline (Table 3).12 In general, all the reactions were
I
N
10
11
12
Cl
F
86
84
Cl
F
very clean, and the N-aryl pyrroles were obtained in high yields un-
der the optimized conditions. The results have shown that substi-
tution played a major role in governing the reactivity of the
substrate.
I
N
81d
I
N
I
N
This protocol efficiently coupled iodo benzenes having electron
t
I
donating groups (e.g., Me, Et, Bu and OMe) with trans-4-hydroxy-
-proline to produce the corresponding products in excellent yields
N
L
13
84
(Table 3, entries 2 and 4–7), whereas in the presence of electron
withdrawing group (NO2) a slight decrease in the yield of the N-
aryl pyrroles (Table 3, entries 15–17) was observed. However,
when sterically demanding ortho substituent is present in the aryl
iodide, the corresponding N-aryl pyrroles were obtained in lower
yields as compared to meta and para substituents (Table 3, entries
6–8 and 15–17) on the ring. Unfortunately, all attempts to couple
I
N
14
15
16
90
78
70
O2N
N
I
O2N
O2N
2-iodo 1,3-dimethyl benzene with trans-4-hydroxy-L-proline have
I
N
O2N
Table 2
I
NO2
N
Cu catalyzed C–N cross-coupling of trans-4-hydroxy-L-proline with different
electrophilesa
17
61
NO2
Entry
Electrophiles
Yieldsb (%)
94
I
18
19
Ph
Ph
84
72
N
I
1
N
I
S
S
BF3K
2
3
0
20
69
N
I
S
S
B(OH)2
Trace
a
Reaction conditions: aryl iodide (1.0 mmol), CuI (20 mol %), DMSO (3.0 mL),
Cs2CO3 (2.5 equiv), trans-4-hydroxy-
L
-proline (2.0 equiv) 110 °C.
b
a
Isolated yield.
Reaction conditions: electrophile (1.0 mmol), trans-4-hydroxy-L-proline
c
No difference in the yield was observed when 4-hydroxy proline was used.
(2.0 mmol) CuI (20 mol %), Cs2CO3 (2.5 equiv), DMSO (3.0 mL), 110 °C, 17 h.
d
b
trans-4-Hydroxy-L-proline (4.0 equiv).
Isolated yield.

V. P. Reddy et al. / Tetrahedron Letters 52 (2011) 777–780
779
reaction takes place only on the carbon atom with the iodo substi-
tuent in the presence of fluoro and chloro (Table 3, entries 10 and
11). Utilizing these conditions, various hetero aromatic iodides
catalyzed C–N cross-coupling reaction with aryl halides to produce
N-aryl pyrroles in moderate to good yields. The reaction outcome
provides a new strategy for constructing N-aryl pyrroles from
were reacted with trans-4-hydroxy-L-proline to give the corre-
trans-4-hydroxy-L-proline. The operational simplicity, inexpen-
sponding N-aryl pyrroles in encouraging yields (Table 3, entries
19 and 20).
siveness, and ready availability of the metal catalyst should render
this protocol attractive both from economic and industrial points
of view as compared to the previous methodologies.
In order to evaluate the scope of the process with respect to the
aryl halides, a variety of substituted aryl bromides and chlorides
were tested under optimized conditions. In all of the cases the
cross-coupling of aryl bromides with trans-4-hydroxy proline fur-
nished the corresponding N-aryl pyrroles derivatives in moderate
to good yields (Table 4).
Acknowledgments
V.P.R. thanks the CSIR, A.V.K. thanks the UGC, New Delhi, for the
award of fellowship.
However, the cross-coupling of various substituted aryl bro-
mides with trans-4-L-hydroxy proline required longer reaction
Supplementary data
times and higher temperatures to get reasonable yields of N-aryl
pyrrole, whereas shorter reaction times and lower temperatures
led to decreased yields (Table 4, entry 2). Poor yields were ob-
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.tetlet.2010.12.016.
served in the coupling of trans-4-hydroxy-L-proline with aryl chlo-
rides (Table 4, entry 1). Further more, C–N cross-coupling of
heterocyclic bromides, such as quinoline, benzodioxane, and thio-
phene produced N-aryl pyrroles in moderate yields (Table 4, en-
tries 8–10). Iodo benzene was found to be a more reactive
substrate than chloro and bromo benzenes.
References and notes
1. (a) Andersen, R. J.; Faulkner, D. J.; Cun-heng, H.; van Duyne, G. D.; Clardy, J. J.
Am. Chem. Soc. 1985, 107, 5492; (b) Jones, A. Pyrroles; Wiley: New York, 1990.
2. (a) Cozzi, P.; Mongelli, N. Curr. Pharm. Des. 1998, 4, 181; (b) Furstner, A.; Szillat,
H.; Gabor, B.; Mynott, R. J. Am. Chem. Soc. 1998, 120, 8305; (c) Bennett, J. W. Adv.
Appl. Microbiol. 2000, 47, 1; (d) Jacobi, P. A.; Coults, L. D.; Guo, J. S.; Leung, S. I. J.
Org. Chem. 2000, 65, 205; (e) Thompson, R. B. FASEB J. 2000, 15, 1671; (f)
Furstner, A. Angew. Chem., Int. Ed. 2003, 42, 3582; (g) Walsh, C. T.; Tsodikova, S.
G.; Jones, A. R. H. Nat. Prod. Rep. 2006, 23, 517; (h) Liu, K.; Lu, H.; Hou, L.; Qi, Z.;
Teixeira, C.; Barbault, F.; Fan, B.-T.; Liu, S.; Jiang, S.; Xie, L. J. Med. Chem. 2008,
51, 7843; (i) Kovtunenko, V. O. CNS Active Drugs [in Ukrainian], Perun, Kiev,
1997.
In conclusion, we have developed for the first time trans-4-hy-
droxy-L-proline as an effective nucleophilic coupling partner in Cu
Table 4
N-Aryl pyrroles synthesis from various aryl halidesa
HO
3. Lee, C.-F.; Yang, L.-M.; Hwu, T.-Y.; Feng, A.-S.; Tseng, J.-C.; Luh, T.-Y. J. Am. Chem.
Soc. 2000, 122, 4992.
CuI, DMSO, Cs2CO3
O
X
Ar
N
Ar
40 h, 125 0
C
4. (a) Dieter, R. K.; Yu, H. Org. Lett. 2000, 2, 2283; (b) Iwasawa, N.; Maeyama, K.;
Saitou, M. J. Am. Chem. Soc. 1997, 119, 1486; (c) Furstner, A.; Weintritt, H.;
Hupperts, A. J. Org. Chem. 1995, 60, 6637; (d) Katritzky, A.; Jiang, J.; Steel, P. J. J.
Org. Chem. 1994, 59, 4551; (e) Hantzsch, A. Chem. Ber. 1890, 23, 1474; (f)
Broadbent, H. S.; Burnharm, W. S.; Olsen, R. K.; Sheely, R. M. J. Heterocycl. Chem.
1968, 5, 757; (g) Bayer, H. O.; Gotthardt, H.; Huisgen, R. Chem. Ber. 1970, 103,
2356; (h) Periasamy, M.; Srinivas, G.; Bharati, P. J. Org. Chem. 1999, 64, 4204.
5. (a) Ruault, P.; Pilard, J.-F.; Touaux, B.; Boullet, F. T.; Hamelin, J. Synlett 1994,
935; (b) Danks, T. N. Tetrahedron Lett. 1999, 40, 3957.
6. (a) Azizian, J.; Karimi, A. R.; Kazemizadeh, Z.; Mohammadi, A. A.;
Mohammadizadeh, A. R. J. Org. Chem. 2005, 70, 1471; (b) Banik, B. K.;
Cardona, M. Tetrahedron Lett. 2006, 47, 7385; (c) Sridhar, R.; Srinivas, B.;
Kumar, V. P.; Reddy, V. P.; Kumar, A. V.; Rao, K. R. Adv. Synth. Catal. 2008, 350,
1489.
N
H
OH
Entry
1
Aryl halide
Product
Yieldb (%)
15
N
Cl
Br
70
48c
N
2
25d
64
Br
N
3
4
5
MeO
MeO
Ph
Br
Br
N
61
60
7. (a) Rivera, S.; Bandyopadhyay, D.; Banik, B. K. Tetrahedron Lett. 2009, 50, 5445;
(b) Bandyopadhyay, D.; Mukherjee, S.; Banik, B. K. Molecules 2010, 15, 2520; (c)
Polshettiwar, V.; Varma, R. S. Tetrahedron 2010, 66, 1091; (d) Wilson, M. A.;
Filzen, G.; Welmaker, G. S. Tetrahedron Lett. 2009, 50, 4807.
N
Ph
Br
8. (a) Correa, A.; Bolm, C. Adv. Synth. Catal. 2007, 349, 2673; (b) Taillefer, M.; Xia,
N.; Ouali, A. Angew. Chem., Int. Ed. 2007, 46, 934; (c) Cristau, H.-J.; Cellier, P. P.;
Spindler, J.-F.; Taillefer, M. Chem. Eur. J. 2004, 10, 5607; (d) Huang, H.; Yan, X.;
Zhu, W.; Liu, H.; Jiang, H.; Chen, K. J. Comb. Chem. 2008, 10, 617; (e) Zhu, L.;
Cheng, L.; Zhang, Y.; Xie, R.; You, J. J. Org. Chem. 2007, 72, 2737; (f) Ma, H.-C.;
Jiang, X.-Z. J. Org. Chem. 2007, 72, 8943; (g) Rout, L.; Jammi, S.; Punniyamurthy,
T. Org. Lett. 2007, 9, 3397; (h) Huang, Y.-Z.; Miao, H.; Zhang, Q.-H.; Chen, C.; Xu,
J. Catal. Lett. 2008, 122, 344; (i) Huang, Y.-Z.; Gao, J.; Ma, H.; Miao, H.; Xu, J.
Tetrahedron Lett. 2008, 49, 948; (j) Chang, J. W. W.; Xu, X.; Chan, P. W. H.
Tetrahedron Lett. 2007, 48, 245; (k) Deng, W.; Wang, Y. F.; Zhang, C.; Liu, L.; Guo,
Q. X. Chin. Chem. Lett. 2006, 17, 313; (l) Kantam, M. L.; Yadav, J.; Laha, S.;
Sreedhar, B.; Jha, S. Adv. Synth. Catal. 2007, 349, 1938.
9. Xu, H.-J.; Zheng, F.-Y.; Liang, Y.-F.; Cai, Z.-Y.; Feng, Y.-S.; Che, D.-Q. Tetrahedron
Lett. 2010, 51, 669.
10. (a) Petersen, M.; Keiner, A. Green Chem. 1999, 99; (b) Sweeney, S. M.; Korkko, J.;
Ala-kokko, L.; Antomo, J. D. S. J. Biol. Chem. 2002, 277, 4223.
11. (a) Reddy, V. P.; Swapna, K.; Kumar, A. V.; Rao, K. R. J. Org. Chem. 2009, 74, 3189;
(b) Swapna, K.; Kumar, A. V.; Reddy, V. P.; Rao, K. R. J. Org. Chem. 2009, 74,
7514; (c) Reddy, V. P.; Kumar, A. V.; Swapna, K.; Rao, K. R. Org. Lett. 2009, 11,
951; (d) Reddy, V. P.; Kumar, A. V.; Swapna, K.; Rao, K. R. Org. Lett. 2009, 11,
1697; (e) Reddy, V. P.; Kumar, A. V.; Swapna, K.; Rao, K. R. Synlett 2009, 2783;
(f) Reddy, V. P.; Kumar, A. V.; Rao, K. R. Chem. Lett. 2010, 39, 212; (g) Reddy, V.
P.; Kumar, A. V.; Rao, K. R. Tetrahedron Lett. 2010, 51, 3181.
N
6
57
Br
N
7
8
67
54
Br
Br
N
N
N
N
O
O
O
9
51
59
O
10
N
Br
S
S
a
Reaction conditions: aryl halides (1.0 mmol), CuI (20 mol %), DMSO (3.0 mL),
12. General procedure for the synthesis of N-aryl pyrroles: to a stirred solution of iodo
Cs2CO3 (2.5 equiv), trans-4-hydroxy-
L-proline (2.0 equiv), 125 °C, 40 h.
benzene (1.0 mmol) and trans-4-hydroxy-L-proline (2.0 equiv) in dry DMSO
b
Isolated yield.
24 h.
(3.0 mL) at rt was added CuI (20 mol %) followed by Cs2CO3 (2.5 equiv) and
heated at 110 °C for 24 h. The progress of the reaction was monitored by TLC.
After the reaction was complete, the reaction mixture was allowed to cool, and
c
d
At 110 °C.

780
V. P. Reddy et al. / Tetrahedron Letters 52 (2011) 777–780
a 1:1 mixture of ethyl acetate/water (20 mL) was added. The combined organic
1-(5-Methylthiophen-2-yl)-1H-pyrrole (Table 3, entry 17): white solid; mp 87–
91 °C; 1H NMR (300 MHz, CDCl3): d = 6.85 (t, 2H, J = 2.0 Hz), 6.62–6.61 (m, 1H),
6.52–6.51 (m, 1H), 6.19 (t, 2H, J = 2.0 Hz), 2.44 (s, 3H); 13C NMR (75 MHz,
CDCl3): d = 141.8, 133.9, 123.7, 121.2, 115.7, 110, 15.3; Anal Calcd for C9H9NS:
C, 66.22; H, 5.56; N, 8.58; S, 19.64. Found: C, 66.16; H, 5.48; N, 8.49; S, 19.56.
1-(Thiophen-2-yl)-1H-pyrrole (Table 3, entry 18): white solid; mp 75-78 °C; 1H
NMR (300 MHz, CDCl3): d = 6.96–6.82 (m, 5H), 6.22–6.18 (m, 2H); 13C NMR
(75 MHz, CDCl3): d = 150.5, 126.0, 121.3, 119.1, 115.4, 110.4; Anal Calcd for
C8H7NS: C, 64.39; H, 4.73; N, 9.39; S, 21.49. Found: C, 64.28; H, 4.65; N, 9.31; S,
21.41.
extracts were dried with anhydrous Na2SO4. The solvent and volatiles were
completely removed under vacuum to give the crude product, which was
purified by column chromatography on silica gel (petroleum ether/ethyl
acetate, 9:1) to afford the corresponding coupling product. The identity and
purity of the product was confirmed by 1H and 13C NMR spectroscopic
analyses.
Data of representative examples: 1-phenyl-1H-pyrrole (Table 3, entry 1): white
solid; mp 58–61 °C; 1H NMR (300 MHz, CDCl3): d = 7.43–7.36 (m, 4H), 7.24–
7.17 (m, 1H), 7.05 (t, 2H, J = 2.66 Hz), 6.31 (t, 2H, J = 2.66 Hz); 13C NMR
(75 MHz, CDCl3): d = 129.4, 125.3, 120.7, 119.2, 110.3.
1-(Anthracen-9-yl)-1H-pyrrole (Table 4, entry 6): white solid; mp 149–153 °C;
1H NMR (300 MHz, CDCl3): d = 8.48 (s, 1H), 7.99 (d, 2H, J = 7.76 Hz), 7.54–7.37
(m, 6H), 6.94 (t, 2H, J = 2.26 Hz), 6.44 (t, 2H, J = 2.26 Hz); 13C NMR (75 MHz,
CDCl3): d = 133.4, 131.3, 129.1, 128.0, 127.2, 126.8, 125.6, 125.2, 124.4, 123.3,
108.8; Anal Calcd for C18H13N: C, 88.86; H, 5.39; N, 5.76. Found: C, 88.79; H,
5.31; N, 5.69.
1-(4-Ethylphenyl)-1H-pyrrole (Table 3, entry 4): white solid; mp 67–70 °C; 1H
NMR (300 MHz, CDCl3): d = 7.26 (d, 2H, J = 8.02 Hz), 7.19 (d, 2H, J = 8.02 Hz),
7.008–7.004 (m, 2H), 6.28 (t, 2H, J = 2.26 Hz), 2.64 (q, 2H, J = 7.13 Hz), 1.25 (t,
3H, J = 7.13 Hz); 13C NMR (75 MHz, CDCl3): d = 141.4, 139.0, 128.8, 120.7,
119.1, 110.4, 28.4, 15.8; Anal Calcd for C12H13N: C, 84.17; H, 7.65; N, 8.18.
Found: C, 84.09; H, 7.57; N, 8.11.
3-(1H-Pyrrol-1-yl) quinoline (Table 4, entry 8): white solid; mp 69-74 °C; 1H
NMR (300 MHz, CDCl3): d = 9.06 (d, 1H, J = 2.64 Hz), 8.11 (d, 1H, J = 8.98 Hz),
8.04–8.02 (m, 1H), 7.82–7.80 (m, 1H), 7.70–7.65 (m, 1H), 7.59–7.54 (m, 1H),
7.17 (t, 2H, J = 2.64 Hz), 6.39 (t, 2H, J = 2.64 Hz); 13C NMR (75 MHz, CDCl3):
d = 144.5, 129.5, 128.9, 127.7, 127.4, 124.6, 119.4, 111.6; Anal Calcd for
1-(4-(Benzyloxy)phenyl)-1H-pyrrole (Table 3, entry 9): white solid; mp 102–
105 °C; 1H NMR (300 MHz, CDCl3): d = 7.40–7.21 (m, 8H), 6.95 (d, 2H,
J = 8.30 Hz), 6.91 (q, 2H, J = 2.26 Hz), 6.22 (t, 1H, J = 2.26 Hz), 5.06 (s, 2H); 13C
NMR (75 MHz, CDCl3): d = 156.6, 136.7, 134.6, 129.4, 128.5, 128.0, 127.4, 122.0,
120.9, 119.5, 115.7, 114.7, 109.8, 70.3; Anal Calcd for C17H15NO: C, 81.24; H,
6.06; N, 5.62. Found: C, 81.16; H, 5.98; N, 5.56.
1,4-Di(1H-pyrrol-1-yl)benzene (Table 3, entry 12): white solid; mp 234–238 °C;
1H NMR (300 MHz, CDCl3): d = 7.42–7.41 (m, 4H), 7.00 (t, 4H, J = 2.06 Hz), 6.28
(t, 4H, J = 2.06 Hz); 13C NMR (75 MHz, CDCl3): d = 138.5, 121.5, 119.2, 110.8;
Anal Calcd for C14H12N2: C, 80.74; H, 5.81; N, 13.45. Found: C, 80.68; H, 5.74; N,
13.39.
C
13H10N2: C, 80.39; H, 5.19; N, 14.42. Found: C, 80.28; H, 5.11; N, 14.36.
1-(2,3-Dihydrobenzo[b][1,4]dioxin-6-yl)-1H-pyrrole (Table 4, entry 9): white
solid; mp 94–97 °C; 1H NMR (300 MHz, CDCl3): d = 6.90 (t, 2H, J = 2.07 Hz),
6.85–6.83 (m, 3H), 6.24 (t, 2H, J = 2.07 Hz), 4.27–4.26 (m, 4H); 13C NMR
(75 MHz, CDCl3): d = 143.8, 141.5, 134.8, 119.5, 117.7, 113.7, 110.0, 109.9, 64.4,
64.2; Anal Calcd for C12H11NO2: C, 71.63; H, 5.51; N, 6.96. Found: C, 71.55; H,
5.42; N, 6.89.