A novel method for the synthesis of dipyrromethanes by metal triflate catalysis

Article abstract of DOI:10.1016/j.tet.2006.08.047

5-Substituted dipyrromethanes were synthesized by the reaction of N-tosyl imines with excess pyrrole in the presence of metal triflates. Tripyrromethane and other oligomeric side products were not observed. High yields of 5-substituted dipyrromethanes wer

Full text of DOI:10.1016/j.tet.2006.08.047

Tetrahedron 62 (2006) 10130–10135
A novel method for the synthesis of dipyrromethanes
by metal triflate catalysis
*
Baris Temelli and Canan Unaleroglu
Hacettepe University, Department of Chemistry, 06532 Ankara, Turkey
Received 18 April 2006; revised 2 August 2006; accepted 11 August 2006
Available online 1 September 2006
Abstract—5-Substituted dipyrromethanes were synthesized by the reaction of N-tosyl imines with excess pyrrole in the presence of metal
triflates. Tripyrromethane and other oligomeric side products were not observed. High yields of 5-substituted dipyrromethanes were obtained
for electron donating and withdrawing substituents by performing the reaction at two different temperatures. The new reaction procedure is
simple and anhydrous conditions are not required.
Ó 2006 Elsevier Ltd. All rights reserved.
1. Introduction
excess pyrrole by using catalytic amounts of metal triflate
(Scheme 1).
5-Substituted dipyrromethanes are important precursors
for the synthesis of meso-substituted porphyrins, corroles,
expanded and reduced porphyrins and related compounds
such as dipyrrins, calixpyrroles and chlorins.1 The first
one-flask synthesis of dipyrromethanes was reported in
1994.2 In the past decade, a number of methods have then
been developed for the synthesis and purification of dipyrro-
methanes.3 Almost all the methods consist of the condensa-
tion of an aldehyde and pyrrole in the presence of various
acids such as BF3$etherate, trifluoroacetic acid (TFA),
propionic acid and p-toluenesulfonic acid. These studies
mostly afford moderate yields of meso-substituted dipyrro-
methanes. The yields are reduced due to the formation of
oligomeric products, which make the purification of the
dipyrromethanes from the reaction medium difficult.
R
Ts
N
10% M(OTf)X
H
+
N
H
HN
NH
R
R= H, 4-CH3O, 2-CH3O, 4-CH3, 2-OH,
4-NO2, 4-CF3, 4-F, 4-Cl, 4-Br
Scheme 1.
2. Results and discussion
Equimolar concentrations of pyrrole (1) and N-benzylidene-
4-methylbenzenesulfonamide (2a) undergo a Cu(OTf)2 cat-
alyzed regioselective addition reaction in THF at rt to afford
4-methyl-N-(phenyl(1H-pyrrol-2-yl)methyl)benzenesulfon-
amide (4a). Increasing the molar ratio of pyrrole, to N-tosyl
imine 2a, to 2:1 gave 4a in higher yield with the formation
of 5-phenyldipyrromethane (3a) as a minor product.6 After
this examination, we focused on obtaining the 5-substituted
dipyrromethane as the major product from the reaction of
pyrrole and N-benzylidene-4-methylbenzenesulfonamide
(2a). We performed the reaction of pyrrole with 2a by using
different pyrrole/N-tosyl imine ratios in the presence of
copper triflate (10 mol %) at rt. Reactions with 10 and
20 equiv of pyrrole were carried out in THF, monitored with
TLC and completed after 6 h, affording 3a/4a with 34/37
and 40/32% yields, respectively (Scheme 2). When the reac-
tion was performed with 40 equiv of pyrrole without solvent,
Metal triflate catalyzed reactions are currently of great inter-
est in organic chemistry. They have been used as water-
stable and reuseable Lewis acids in several carbon–carbon
bond forming reactions such as aldol, Michael, Diels–Alder
and Friedel–Crafts acylation and alkylations.4 Recently, we
reported the metal triflate catalyzed addition of pyrroles to
a,b-unsaturated esters.5 We also examined the reactions of
pyrrole with N-tosyl imines in the presence of catalytic
amounts of metal triflates to obtain pyrrole-substituted sul-
fonamides.6 In connection with this study, we report here
a novel and an efficient method for preparing 5-substituted
dipyrromethanes from the reaction of N-tosyl imines and
Keywords: Dipyrromethanes; Metal triflate; N-Tosyl imine; Pyrrole deriva-
tives; Lewis acid catalysis.
* Corresponding author. Tel.: +90 312 297 7962; fax: +90 312 299 2163;
e-mail: canan@hacettepe.edu.tr
0040–4020/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2006.08.047

B. Temelli, C. Unaleroglu / Tetrahedron 62 (2006) 10130–10135
10131
Table 2. Synthesis of 5-substituted dipyrromethanes by the reaction of
pyrrole and different N-tosyl iminesa
dipyrromethane was formed as the major product in 55%
yield. Increasing the pyrrole equivalent did not obviously
affect the yield of 3a.
R
R
Ts
N
Ts
N
10% M(OTf)X
H
+
+
10% M(OTf)x
N
H
N
H
H
+
+
HN
HN
NH
N
H
Ts
R
N
H
HN
HN
NH
Ts
1
2a-j
4a-j
3a-j
1
2a
3a
4a
Entry R
Catalyst Gd(OTf)3 Catalyst Cu(OTf)2 Compounds
Yield (%)b 3/4
Scheme 2.
Yield (%)b 3/4
To investigate the effects of metal triflates, the reactions of
pyrrole and N-benzylidene-4-methylbenzenesulfonamide
(2a) were carried out in the presence of different metal tri-
flates with excess pyrrole (40 equiv) at rt. Among all the
metal triflates tested, Gd(OTf)3 and Cu(OTf)2 gave the high-
est yields of 5-phenyldipyrromethane (3a), 69 and 55%,
respectively (Table 1).
rt
100 ꢀC
rt
100 ꢀC
1
2
3
4
5
6
7
8
H
69/20
65/17
64/15
61/21
69/9
44/—
79/8
68/13
70/14
71/13
74/12
55/16
85/8
55/20
80/7
77/—
7/78
5/86
38/45
40/55
38/53
48/10
45/19
48/35
35/11
27/—
72/9
3a/4a
3b/4b
3c/4c
3d/4d
3e/4ec
3f/4f
3g/4g
3h/4h
3i/4i
4-CH3O 83/10
2-CH3O 71/17
4-CH3 83/10
90/—
4-NO2 5/85
2-OH
4-CF3
4-F
4-Cl
4-Br
11/82
40/50
44/46
20/71
85/6
53/32
62/25
74/14
Table 1. Effects of metal triflates on the synthesis of dipyrromethane 3aa
9
10
3j/4j
Entry
Catalyst
Yield (%)b 3a/4a
a
Reactions were carried out in excess pyrrole (40 equiv) as solvent.
Yield refers to pure product after column chromatography.
Addition product decomposed and could not be isolated by column chro-
matography.
b
c
1
2
3
4
5
6
7
Cu(OTf)2
Gd(OTf)3
Yb(OTf)3
Y(OTf)3
La(OTf)3
Zn(OTf)2
Nd(OTf)3
55/16
69/20
52/38
45/43
34/53
23/60
14/72
substituents only by performing the reaction at two different
temperatures.
a
Reactions were carried out in excess pyrrole (40 equiv) as solvent at rt.
Yield refers to pure product after column chromatography.
b
Structures of dipyrromethanes 3a–d, f, h–j were confirmed
by comparing their NMR spectra and melting points with
those reported in literature.2,7 Structures of 3e, g and pyrrole
derivatives 4a–j were identified by 1H NMR, 13C NMR and
elemental analysis. The position of the substituent was as-
signed by COSY spectra and by comparison of the 1H
NMR spectra with the known 2-alkylated pyrroles.8
We continued to study the effect of substituents on the phenyl
ring of the N-tosyl imines using Cu(OTf)2 and Gd(OTf)3 on
the synthesis of 5-substituted dipyrromethanes. Reactions of
N-tosyl imines (2a–j) and pyrrole with Gd(OTf)3 catalyst
gave 2-alkylated pyrrole sulfonamides (4a–j) in 10–85%
yields and 5-substituted dipyrromethanes (3a–j) in 5–90%
yields (Table 2). Similar results were obtained when
Cu(OTf)2 was used as the catalyst at rt; the corresponding
pyrrole derivatives were obtained in 7–86% yields and dipyr-
romethanes in 5–85% yields. For both catalysts, formation of
the products 3 and 4 is very sensitive to the nature of the sub-
stituents on N-tosyl imine. When the phenyl ring bears an
electron donating substituent such as a methyl, hydroxy or
methoxy, dipyrromethanes 3 are obtained in high yields
(Table 2, entries 2–5). The reactions with electron withdraw-
ing groups such as nitro, trifluoromethyl or halogens on the
phenyl ring gave 5-substituted dipyrromethanes in lower
yields at rt (Table 2, entries 6–10).
The following reaction mechanism is proposed for the metal
triflate catalyzed reaction of N-tosyl imine with pyrrole
(Scheme 3). In the first step, N-tosyl imine is activated by
the metal triflate. The addition of pyrrole to the activated im-
ine complex affords structure 4a through the intermediate 5.
Formation of dipyrromethane could be explained by the
addition of a second pyrrole to the intermediate 6, which is
generated by the elimination of sulfonamide from intermedi-
ate 5 or compound 4a. Structures like intermediate 6 are pro-
posed by other researchers for the reaction of indole with
imines, aldehydes and enones.9 To support this proposed
mechanism, the isolated product 4a was reacted with excess
pyrrole in the presence of metal triflate. Dipyrromethane was
obtained as the main product after 6 h under the same condi-
tions and p-toluenesulfonamide was isolated. The same reac-
tion was performed without using the metal triflate and
dipyrromethane formation was not observed. This examina-
tion shows that the metal triflate has a crucial role in the
formation of dipyrromethane from 4a.
To improve the yields of dipyrromethane products having
electron withdrawing substituents, reactions were carried
out at 100 ꢀC. It was observed that at high temperatures
the yields of dipyrromethane products with electron with-
drawing substituents and halogens increase dramatically
(Table 2, entries 6–10). Dipyrromethanes with strongly elec-
tron withdrawing groups (nitro, trifluoromethyl) and halo-
gens were synthesized in 68–79% yields with Gd(OTf)3
and in 53–85% yields with Cu(OTf)2. Despite this increase
for electron withdrawing groups at 100 ꢀC, yields for elec-
tron donating groups are lower. With this reaction protocol,
we obtained high yields of dipyrromethanes for both types of
3. Conclusion
In conclusion, a new and attractive synthetic method has
been developed for the preparation of 5-substituted dipyrro-
methanes by the reaction of N-tosyl imine and pyrrole in the

10132
B. Temelli, C. Unaleroglu / Tetrahedron 62 (2006) 10130–10135
O
X(TfO)M
S
O
N
O
S
N
N
H
O
S
HN
HN
X(TfO)M
+
O
N
H
O
4a
5
1
2a
M(OTf)x
- NH2Ts
- NH2Ts
N
H
N
HN
3a
NH
X(TfO)M
6
Scheme 3.
presence of metal triflates. Tripyrromethane or any other
oligomeric side products were not observed. The reaction
procedure is simple and anhydrous conditions are not re-
quired. An advantage of this method is that high yields of
5-substituted dipyrromethanes with electron donating or
withdrawing substituents can be obtained selectively only
by tuning the reaction temperature.
(400 MHz, CDCl3): d 5.49 (s, 1H, mesoH), 5.92 (br s, 2H,
2C3-H), 6.14 (dd, J 2.8, 5.9, 2H, 2C4-H), 6.68 (dd, J 2.6,
4.2, 2H, 2C5-H), 7.22–7.35 (m, 5H, Ar-H), 7.88 (br s, 2H,
2N-H); 13C NMR (100 MHz, CDCl3): d 44.10, 107.45,
108.75, 117.12, 127.03, 128.51, 128.68, 132.36, 142.23.
4.2.2. 5-(4-Methoxyphenyl)dipyrromethane (3b).7a Pale
yellow powder; mp: 98–99 ꢀC, lit.: 99 ꢀC; Rf 0.47 (1:3
EtOAc/hexane); IR (KBr) 3405, 2964, 2936, 1616, 1507,
1457, 1299, 1245, 1175, 1103, 1027, 965, 838, 774, 720,
4. Experimental
4.1. General
554 cmꢁ1 1H NMR (400 MHz, CDCl3): d 3.82 (s, 3H,
;
OCH3), 5.42 (s, 1H, mesoH), 5.90–5.92 (m, 2H, 2C3-H),
6.14 (dd, J 2.8, 6.0, 2H, 2C4-H), 6.65–6.67 (m, 2H, 2C5-H),
6.85 (d, J 8.6, 2H, Ar-H), 7.14 (d, J 8.6, 2H, Ar-H), 7.82 (br
s, 2H, 2N-H); 13C NMR (100 MHz): d 43.21, 55.15, 107.27,
108.67, 114.03, 117.02, 129.44, 132.76, 134.29, 158.61.
Commercially available reagents and solvents were used
1
without further purification. H NMR (400 MHz) and 13C
NMR (100 MHz) spectra were recorded using SiMe4 as an
internal reference with Bruker Ultrashield FT NMR spec-
trometer. IR spectra were determined on an Unicam Mattson
1000 FT IR spectrometer. Melting points were recorded on
Gallenkamp melting-point apparatus and are uncorrected.
Thin-layer chromatography was performed with 60F silica
gel plates and flash column chromatography by use of silica
gel 60 F254 (230–400 mesh). The spots were visualized with
UV light (l¼254 nm). N-Tosyl imines (2a–j) are synthe-
sized in high yields by the reaction of p-toluenesulfonamide
and aldehydes in the presence of p-toluenesulfonic acid.
4.2.3. 5-(2-Methoxyphenyl)dipyrromethane (3c).7a Pale
yellow powder; mp: 114–115 ꢀC, lit.: 115 ꢀC; Rf 0.65 (1:3
EtOAc/hexane); IR (KBr) 3425, 1636, 1485, 1242, 1090,
1
1023, 966, 715, 555 cmꢁ1; H NMR (400 MHz, CDCl3):
d 3.83 (s, 3H, OCH3), 5.82 (s, 1H, mesoH), 5.91 (br s, 2H,
2C3-H), 6.15 (d, J 2.5, 2H, 2C4-H), 6.63 (d, J 1.4,
2H, 2C5-H), 6.94–6.97 (m, 2H, Ar-H), 7.12 (d, J 6.8, 1H,
Ar-H), 7.28 (t, J 7.8, 1H, Ar-H), 7.97 (br s, 2H, 2N-H);
13C NMR (100 MHz, CDCl3): d 37.68, 55.74, 107.10,
108.70, 111.24, 116.67, 121.04, 128.07, 129.60, 131.14,
132.47, 156.73.
4.2. Synthesis of dipyrromethanes (3) and 2-substituted
pyrrole sulfonamides (4)
4.2.4. 5-(4-Methylphenyl)dipyrromethane (3d).7b Pale
yellow crystals; mp: 110–111 ꢀC, lit.: 110–111 ꢀC; Rf 0.65
(1:3 EtOAc/hexane); IR (KBr) 3417, 2356, 1635, 1508,
N-Tosyl imine (1 mmol) was dissolved in excess pyrrole
(40 mmol) and then metal triflate (0.1 mmol) was added to
the reaction mixture at the temperature indicated in Table
2. The reaction was monitored with TLC and completed af-
ter 6 h. Metal triflate was removed from the reaction medium
by subjecting the mixture to a short flash silica gel chroma-
tography using ethyl acetate as an eluent. The eluent was re-
moved under reduced pressure and the residue was purified
by flash silica gel chromatography.
1420, 1254, 1089, 1025, 964, 909, 790, 742, 509 cmꢁ1
;
1H NMR (400 MHz, CDCl3): d 2.37 (s, 3H, CH3), 5.44
(s, 1H, mesoH), 5.91 (br s, 2H, 2C3-H), 6.13 (dd, J 2.8,
5.9, 2H, 2C4-H), 6.66 (dd, J 2.6, 4.2, 2H, 2C5-H), 7.10–
7.15 (m, 4H, Ar-H), 7.85 (br s, 2H, 2N-H); 13C NMR
(100 MHz, CDCl3): d 21.18, 43.72, 107.32, 108.74,
116.99, 128.42, 129.38, 132.57, 136.42, 139.25.
4.2.1. 5-Phenyldipyrromethane (3a).7a Pale yellow crys-
tals; mp: 100–101 ꢀC, lit.: 100–101 ꢀC; Rf 0.60 (1:3
EtOAc/hexane); IR (KBr) 3449, 2951, 1630, 1510, 1410,
4.2.5. 5-(2-Hydroxyphenyl)dipyrromethane (3e). Light
brown oil; Rf 0.32 (1:3 EtOAc/hexane); IR (KBr) 3418,
2072, 1635, 1493, 1451, 1330, 1255, 1085, 1023, 909,
1
790, 741, 529 cmꢁ1; H NMR (400 MHz, CDCl3): d 5.17
1293, 1225, 1048, 760, 703, 607 cmꢁ1
;
1H NMR

B. Temelli, C. Unaleroglu / Tetrahedron 62 (2006) 10130–10135
10133
(br s, 1H, OH), 5.53 (s, 1H, mesoH), 6.01 (br s, 2H, 2C3-H),
6.16 (dd, J 2.8, 5.9, 2H, 2C4-H), 6.70 (dd, J 2.6, 4.1, 2H,
2C5-H), 6.87–6.95 (m, 2H, Ar-H), 7.08–7.10 (m, 1H, Ar-
H), 7.18–7.22 (m, 1H, Ar-H), 8.14 (br s, 2H, 2N-H); 13C
NMR (100 MHz, CDCl3): d 40.59, 107.22, 108.85, 117.89,
118.00, 121.63, 128.52, 128.81, 130.19, 130.78, 153.87.
Anal. Calcd for C15H14N2O: C, 75.61; H, 5.92; N, 11.76.
Found: C, 75.48; H, 6.03; N, 11.58.
J 8.4, 2H, Ar-H), 7.46 (d, J 8.4, 2H, Ar-H), 7.80 (br s, 2H,
2N-H); 13C NMR (100 MHz, CDCl3): d 43.50, 107.65,
108.83, 117.44, 120.95, 130.17, 131.71, 131.77, 141.27.
4.2.11. 4-Methyl-N-(phenyl(1H-pyrrol-2-yl)methyl)-
benzenesulfonamide (4a). White powder; mp: 132–
133 ꢀC; Rf 0.40 (1:3 EtOAc/hexane); IR (KBr): 3458,
2085, 1633, 1390, 1282, 1136, 1080, 1021, 689, 605,
531 cmꢁ1 1H NMR (400 MHz, CDCl3): d 2.38 (s, 3H,
;
4.2.6. 5-(4-Nitrophenyl)dipyrromethane (3f).7a Yellow
powder; mp: 159–160 ꢀC, lit.: 159–160 ꢀC; Rf 0.48 (1:3
EtOAc/hexane); IR (KBr) 3394, 3359, 3101, 1595, 1512,
CH3), 5.57–5.60 (m, 2H, C3-H, CH), 5.85 (d, J 9.9, 1H,
SO2NH), 5.97 (dd, J 2.8, 6.0, 1H, C4-H), 6.65 (dd, J 2.5,
4.0, 1H, C5-H), 7.09–7.20 (m, 7H, Ar-H), 7.53 (d, J 8.3,
2H, Ar-H), 8.76 (br s, 1H, NH); 13C NMR (100 MHz,
CDCl3): d 21.49, 55.78, 108.20, 118.57, 127.16, 127.38,
127.57, 128.35, 129.05, 129.29, 130.53, 137.47, 138.89,
142.87. Anal. Calcd for C18H18N2O2S: C, 66.23; H, 5.56;
N, 8.58; S, 9.82. Found: C, 66.12; H, 5.63; N, 8.40; S, 9.73.
1348, 1114, 1027, 808, 735, 660, 568 cmꢁ1 1H NMR
;
(400 MHz, CDCl3): d 5.59 (s, 1H, mesoH), 5.88 (br s, 2H,
2C3-H), 6.18 (dd, J 2.8, 6.0, 2H, 2C4-H), 6.75 (dd, J 2.6,
4.2, 2H, 2C5-H), 7.39 (d, J 8.6, 2H, Ar-H), 7.98 (br s, 2H,
2N-H), 8.18 (d, J 8.8, 2H, Ar-H); 13C NMR (100 MHz,
CDCl3): d 43.87, 107.92, 108.95, 117.94, 123.80, 129.25,
130.76, 147.02, 149.66.
4.2.12. N-((4-Methoxyphenyl)(1H-pyrrol-2-yl)methyl)-4-
methylbenzenesulfonamide (4b). Colourless viscous oil; Rf
0.30 (1:3 EtOAc/hexane); IR (KBr): 3516, 2072, 1636, 1507,
1243, 1169, 1027, 762, 715, 556 cmꢁ1; 1H NMR (400 MHz,
CDCl3): d 2.40 (s, 3H, CH3), 3.77 (s, 3H, OCH3), 5.50 (d,
J 8.1, 1H, CH), 5.57–5.59 (m, 2H, SO2NH, C3-H), 5.98
(dd, J 2.7, 6.0, 1H, C4-H), 6.67 (br s, 1H, C5-H), 6.70 (d,
J 8.7, 2H, Ar-H), 7.02 (d, J 8.7, 2H, Ar-H), 7.14 (d, J 8.2,
2H, Ar-H), 7.55 (d, J 8.3, 2H, Ar-H), 7.84 (d, J 8.4, 2H,
Ar-H), 8.72 (br s, 1H, NH); 13C NMR (100 MHz, CDCl3):
d 21.55, 55.09, 55.53, 108.08, 108.19, 113.79, 118.51,
127.25, 128.04, 129.03, 130.90, 131.06, 137.54, 142.88,
159.19. Anal. Calcd for C19H20N2O3S: C, 64.02; H, 5.66;
N, 7.86; S, 9.00. Found: C, 64.25; H, 5.63; N, 7.88; S, 9.08.
4.2.7. 5-(4-Trifluoromethylphenyl)dipyrromethane (3g).
Yellow oil; Rf 0.47 (1:3 EtOAc/hexane); IR (KBr) 3448,
3401, 2980, 1618, 1416, 1326, 1164, 1124, 1067, 1019,
1
775, 722 cmꢁ1; H NMR (400 MHz, CDCl3): d 5.51 (s,
1H, mesoH), 5.91 (br s, 2H, 2C3-H), 6.20 (dd, J 2.8, 6.0,
2H, 2C4-H), 6.67–6.69 (m, 2H, 2C5-H), 7.35 (d, J 8.3, 2H,
Ar-H), 7.63 (d, J 8.1, 2H, Ar-H), 7.82 (br s, 2H, 2N-H);
13C NMR (100 MHz, CDCl3): d 43.78, 107.84, 108.82,
1
3
117.66, 124.16 (q, JC–F 270.3), 125.54 (q, JC–F 3.7),
128.75, 129.29 (q, 2JC–F 32.2), 131.50, 146.28. Anal. Calcd
for C16H13F3N2: C, 66.20; H, 4.51; N, 9.65. Found: C, 66.07;
H, 4.70; N, 9.59.
4.2.8. 5-(4-Fluorophenyl)dipyrromethane (3h).7a Light
brown crystals; mp: 80–81 ꢀC, lit.: 81 ꢀC; Rf 0.53 (1:3
EtOAc/hexane); IR (KBr) 3410, 2928, 1610, 1498, 1451,
4.2.13. N-((2-Methoxyphenyl)(1H-pyrrol-2-yl)methyl)-4-
methylbenzenesulfonamide (4c). Light brown powder; mp:
132–133 ꢀC; Rf 0.34 (1:3 EtOAc/hexane); IR (KBr): 3440,
2954, 2835, 1638, 1491, 1453, 1328, 1247, 1156, 1092,
1285, 1175, 1103, 960, 764, 554 cmꢁ1
;
1H NMR
1
(400 MHz, CDCl3): d 5.45 (s, 1H, mesoH), 5.89 (br s,
2H, 2C3-H), 6.16 (dd, J 2.8, 5.8, 2H, 2C4-H), 6.66 (br s,
2H, 2C5-H), 7.00–7.05 (m, 2H, Ar-H), 7.16–7.20 (m, 2H,
Ar-H), 7.81 (br s, 2H, 2N-H); 13C NMR (100 MHz,
1023, 909, 790, 743, 664, 549 cmꢁ1; H NMR (400 MHz,
CDCl3): d 2.37 (s, 3H, CH3), 3.70 (s, 3H, OCH3), 5.51 (br
s, 1H, C3-H), 5.64 (d, J 9.3, 1H, CH), 5.90 (d, J 9.1, 1H,
SO2NH), 5.97 (dd, J 2.8, 5.8, 1H, C4-H), 6.70 (dd, J 2.5,
4.1, 1H, C5-H), 6.73 (d, J 8.3, 1H, Ar-H), 6.81 (t, J 7.4,
1H, Ar-H), 7.00 (dd, J 1.6, 7.5, 1H, Ar-H), 7.09 (d, J 8.2,
2H, Ar-H), 7.16–7.21 (m, 1H, Ar-H), 7.55 (d, J 8.2, 2H,
Ar-H), 8.72 (br s, 1H, NH); 13C NMR (100 MHz, CDCl3):
d 21.55, 53.85, 55.45, 107.04, 108.26, 111.21, 118.01,
120.87, 126.82, 127.22, 129.09, 129.60, 130.55, 137.86,
142.55, 156.76. Anal. Calcd for C19H20N2O3S: C, 64.02;
H, 5.66; N, 7.86; S, 9.00. Found: C, 64.11; H, 5.81; N,
7.82; S, 8.75.
2
CDCl3): d 43.28, 107.55, 108.79, 115.42 (d, JC–F 21.3),
117.34, 129.92 (d, JC–F 7.9), 132.24, 137.96 (d, JC–F
3
4
3.2), 161.85 (d, 1JC–F 244.5).
4.2.9. 5-(4-Chlorophenyl)dipyrromethane (3i).7b Pale
yellow powder; mp: 112–113 ꢀC, lit.: 112 ꢀC; Rf 0.58 (1:3
EtOAc/hexane); IR (KBr) 3382, 2958, 2923, 2861, 1641,
1485, 1405, 1255, 1087, 1022, 767, 720, 550, 508 cmꢁ1
;
1H NMR (400 MHz, CDCl3): d 5.42 (s, 1H, mesoH), 5.90
(br s, 2H, 2C3-H), 6.17 (dd, J 2.8, 5.8, 2H, 2C4-H), 6.66
(dd, J 2.6, 4.2, 2H, 2C5-H), 7.15 (d, J 8.4, 2H, Ar-H), 7.31
(d, J 8.4, 2H, Ar-H), 7.80 (br s, 2H, 2N-H); 13C NMR
(100 MHz, CDCl3): d 43.35, 107.61, 108.75, 117.42,
128.70, 129.74, 131.88, 132.81, 140.69.
4.2.14. N-((1H-Pyrrol-2-yl)(p-tolyl)methyl)-4-methyl-
benzenesulfonamide (4d). Light brown powder; mp: 96–
97 ꢀC; Rf 0.44 (1:3 EtOAc/hexane); IR (KBr): 3426, 2963,
2924, 2866, 2104, 1636, 1509, 1426, 1321, 1262, 1154,
1091, 1026, 910, 790, 722, 663, 563 cmꢁ1 1H NMR
;
4.2.10. 5-(4-Bromophenyl)dipyrromethane (3j).2 Pale
yellow powder; mp: 122–123 ꢀC, lit.: 125–125.5 ꢀC; Rf
0.59 (1:3 EtOAc/hexane); IR (KBr) 3374, 3098, 2957,
2920, 2861, 1707, 1481, 1400, 1083, 1021, 765, 720, 643,
(400 MHz, CDCl3): d 2.34 (s, 3H, CH3), 2.43 (s, 3H,
SO2Ph-CH3), 5.52 (d, J 8.2, 1H, CH), 5.58 (br s, 1H,
C3-H), 5.62 (d, J 8.0, 1H, SO2NH), 5.98 (dd, J 2.8, 5.7,
1H, C4-H), 6.66 (br s, 1H, C5-H), 7.00–7.02 (m, 4H,
Ar-H), 7.13 (d, J 8.1, 2H, Ar-H), 7.55 (d, J 8.2, 2H, Ar-H),
8.62 (br s, 1H, NH); 13C NMR (100 MHz, CDCl3):
d 21.15, 21.53, 55.64, 108.13, 108.17, 118.51, 127.24,
1
544, 503 cmꢁ1; H NMR (400 MHz, CDCl3): d 5.41 (s,
1H, mesoH), 5.90 (br s, 2H, 2C3-H), 6.16 (dd, J 2.8, 5.9,
2H, 2C4-H), 6.66 (dd, J 2.6, 4.2, 2H, 2C5-H), 7.10 (d,

10134
B. Temelli, C. Unaleroglu / Tetrahedron 62 (2006) 10130–10135
127.37, 129.06, 129.31, 130.78, 135.98, 137.27, 137.55,
142.83. Anal. Calcd for C19H20N2O2S: C, 67.03; H,
5.92; N, 8.23; S, 9.42. Found: C, 66.90; H, 5.95; N, 8.20;
S, 9.37.
7.11–7.13 (m, 4H, Ar-H), 7.49 (d, J 8.3, 2H, Ar-H), 8.79
(br s, 1H, NH); 13C NMR (100 MHz, CDCl3): d 21.53,
55.34, 108.27, 108.40, 118.91, 127.13, 128.44, 128.89,
129.40, 129.92, 133.60, 137.26, 137.32, 143.23. Anal. Calcd
for C18H17ClN2O2S: C, 59.91; H, 4.75; N, 7.76; S, 8.89.
Found: C, 59.67; H, 4.70; N, 7.82; S, 8.78.
4.2.15. 4-Methyl-N-((4-nitrophenyl)(1H-pyrrol-2-yl)-
methyl)benzenesulfonamide (4f). Light brown powder;
mp: 153–154 ꢀC; Rf 0.34 (1:3 EtOAc/hexane); IR (KBr):
3419, 1716, 1636, 1512, 1412, 1337, 1255, 1150, 1089,
4.2.19. N-((4-Bromophenyl)(1H-pyrrol-2-yl)methyl)-4-
methylbenzenesulfonamide (4j). Brown powder; mp:
116–117 ꢀC; Rf 0.42 (1:3 EtOAc/hexane); IR (KBr): 3388,
3275, 2961, 2921, 2862, 2756, 1691, 1596, 1484, 1432,
1
1014, 909, 791, 741, 688, 549 cmꢁ1; H NMR (400 MHz,
CDCl3): d 2.43 (s, 3H, CH3), 5.29 (br s, 1H, SO2NH), 5.52
(br s, 1H, C3-H), 5.70 (br s, 1H, CH), 6.02 (dd, J 2.8, 6.0,
1H, C4-H), 6.76 (dd, J 2.6, 4.0, 1H, C5-H), 7.20 (d, J 8.0,
2H, Ar-H), 7.37 (d, J 8.6, 2H, Ar-H), 7.60 (d, J 8.3, 2H,
Ar-H), 8.10 (d, J 8.7, 2H, Ar-H), 8.56 (br s, 1H, NH); 13C
NMR (100 MHz, CDCl3): d 20.93, 55.06, 108.69, 119.38,
123.54, 127.15, 128.16, 128.99, 129.56, 134.98, 137.06,
143.78, 145.64. Anal. Calcd for C18H17N3O4S: C, 58.21;
H, 4.61; N, 11.31; S, 8.63. Found: C, 58.00; H, 4.68; N,
11.38; S, 8.51.
1
1323, 1154, 1088, 1025, 807, 663, 559 cmꢁ1; H NMR
(400 MHz, CDCl3): d 2.40 (s, 3H, CH3), 5.55–5.57 (m,
2H, C3-H, CH), 5.97–6.00 (m, 2H, SO2NH, C4-H) 6.66
(dd, J 2.5, 4.0, 1H, C5-H), 6.98 (d, J 8.4, 2H, Ar-H), 7.10
(d, J 8.1, 2H, Ar-H), 7.26 (d, J 8.4, 2H, Ar-H), 7.47 (d,
J 8.3, 2H, Ar-H), 8.83 (br s, 1H, NH); 13C NMR
(100 MHz, CDCl3): d 21.55, 55.42, 108.27, 108.43, 118.94,
121.70, 127.11, 129.24, 129.41, 129.79, 131.38, 137.20,
137.77, 143.26. Anal. Calcd for C18H17BrN2O2S: C, 53.34;
H, 4.23; N, 6.91; S, 7.91. Found: C, 53.67; H, 4.31;
N, 6.84; S, 7.98.
4.2.16. N-((1H-Pyrrol-2-yl)(4-(trifluoromethyl)phenyl)-
methyl)-4-methylbenzenesulfonamide (4g). White pow-
der; mp: 113–114 ꢀC; Rf 0.38 (1:3 EtOAc/hexane); IR
(KBr): 3382, 3272, 3107, 3061, 2926, 2867, 1918, 1802,
1612, 1489, 1422, 1325, 1160, 1125, 1063, 1026, 915,
Acknowledgements
1
850, 792, 732, 665, 660, 555 cmꢁ1; H NMR (400 MHz,
The authors thank Hacettepe University for financial support
(BAP project 0302601004).
CDCl3): d 2.34 (s, 3H, CH3), 5.55 (br s, 1H, C3-H), 5.69
(d, J 8.6, 1H, CH), 6.00–6.03 (m, 2H, C4-H, SO2NH), 6.69
(br s, 1H, C5-H), 7.07 (d, J 8.1, 2H, Ar-H), 7.24 (d, J 8.1,
2H, Ar-H), 7.39 (d, J 8.2, 2H, Ar-H), 7.47 (d, J 8.2, 2H,
Ar-H), 8.86 (br s, 1H, NH); 13C NMR (100 MHz, CDCl3):
References and notes
3
d 21.32, 55.66, 108.36, 108.61, 119.15, 125.17 (q, JC–F
3.6), 127.05, 127.91, 129.39, 129.49, 129.90 (q, JC–F
1. (a) Pandey, R. K.; Jagerovic, N.; Ryan, M. J.; Dougherty, T. J.;
Smith, K. M. Tetrahedron 1996, 52, 5349–5362; (b) Jasat, A.;
Dolphin, D. Chem. Rev. 1997, 97, 2267–2340; (c) Gale, P. A.;
Anzenbacher, P., Jr.; Sessler, J. L. Coord. Chem. Rev. 2001,
222, 57–102; (d) Sessler, J. L.; Camiolo, S.; Gale, P. A.
Coord. Chem. Rev. 2003, 240, 17–55; (e) Wu, Y.-D.; Wang,
D.-F.; Sessler, J. L. J. Org. Chem. 2001, 66, 3739–3746; (f)
Wagner, R. W.; Johnson, T. E.; Lindsey, J. S. J. Am. Chem.
Soc. 1996, 118, 11166–11180.
2. Lee, C.-H.; Lindsey, J. S. Tetrahedron 1994, 50, 11427–11440.
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J. Am. Chem. Soc. 1994, 116, 4240–4250; (b) Nishino, N.;
Wagner, R. W.; Lindsey, J. S. J. Org. Chem. 1996, 61, 7534–
7544; (c) Casiraghi, G.; Cornia, M.; Zanardi, F.; Rassu, G.;
Ragg, E.; Bortolini, R. J. Org. Chem. 1994, 59, 1801–1808;
(d) Cornia, M.; Binacchi, S.; Del Soldato, T.; Zanardi, F.;
Casiraghi, G. J. Org. Chem. 1995, 60, 4964–4965; (e)
Vigmond, S. J.; Chang, M. C.; Kallury, K. M. R.; Thompson,
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Cornia, M.; Rassu, G.; Del Sante, C.; Spanu, P. Tetrahedron
1992, 48, 5619–5628; (g) Boyle, R. W.; Xie, L. Y.; Dolphin,
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Wagner, R. W.; O’Shea, D. F.; Boyle, P. D.; Lindsey, J. S.
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2
32.2), 137.01, 142.49, 143.46. Anal. Calcd for
C19H17F3N2O2S: C, 57.86; H, 4.34; N, 7.10; S, 8.13. Found:
C, 57.60; H, 4.32; N, 7.13; S, 7.99.
4.2.17. N-((4-Fluorophenyl)(1H-pyrrol-2-yl)methyl)-4-
methylbenzenesulfonamide (4h). Colourless viscous oil;
Rf 0.37 (1:3 EtOAc/hexane); IR (KBr): 3423, 2978, 2922,
2870, 1640, 1505, 1429, 1322, 1223, 1154, 1092, 1029,
1
915, 844, 774, 722, 664, 542 cmꢁ1; H NMR (400 MHz,
CDCl3): d 2.45 (s, 3H, CH3), 5.54 (br s, 1H, C3-H), 5.57
(d, J 8.4, 1H, CH), 5.86 (d, J 8.4, 1H, SO2NH), 5.98 (dd,
J 2.7, 5.9, 1H, C4-H), 6.67 (dd, J 2.6, 4.1, 1H, C5-H), 6.84
(t, J 8.6, 2H, Ar-H), 7.07–7.13 (m, 4H, Ar-H), 7.52 (d,
J 8.3, 2H, Ar-H), 8.77 (br s, 1H, NH); 13C NMR
(100 MHz, CDCl3): d 21.50, 55.27, 108.25, 115.21 (d,
3
2JC–F 21.4), 118.81, 127.15, 129.10 (d, JC–F 8.1), 129.37,
4
130.31, 134.58 (d, JC–F 3.1), 137.35, 143.15, 162.21 (d,
1JC–F 245.7). Anal. Calcd for C18H17FN2O2S: C, 62.77;
H, 4.98; N, 8.13; S, 9.31. Found: C, 62.40; H, 5.01; N,
8.05; S, 9.19.
4.2.18. N-((4-Chlorophenyl)(1H-pyrrol-2-yl)methyl)-4-
methylbenzenesulfonamide (4i). Brown powder; mp:
115–116 ꢀC; Rf 0.43 (1:3 EtOAc/hexane); IR (KBr): 3448,
3405, 2965, 2922, 2863, 1636, 1332, 1155, 1087, 1022,
1
805, 721, 662, 561 cmꢁ1; H NMR (400 MHz, CDCl3):
d 2.40 (s, 3H, CH3), 5.54–5.57 (m, 2H, C3-H, CH), 5.88
(d, J 8.5, 1H, SO2NH), 5.98 (dd, J 2.7, 6.0, 1H, C4-H),
6.65–6.66 (m, 1H, C5-H), 7.05 (d, J 8.5, 2H, Ar-H),
4. (a) Kobayashi, S.; Sugiura, M.; Kitagawa, H.; Lam, W. W.-L.
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10135
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