Reaction between 4-Nitro-1,3-diarylbutan-1-ones and Ammonium Acetate in the Presence of Morpholine and Sulfur: An Efficient Synthesis of 2,4-Diarylpyrroles

Article abstract of DOI:10.1055/s-0035-1561852

An efficient synthesis of 2,4-diarylpyrroles is described. Heating a mixture of a 4-nitro-1,3-diarylbutan-1-one and ammonium acetate in the presence of morpholine and sulfur afforded the corresponding 2,4-diarylpyrroles in excellent yields.

Full text of DOI:10.1055/s-0035-1561852

SYNLETT
0
9
3
6
-
5
2
1
4
1
4
3
7
-
2
0
9
6
© Georg Thieme Verlag Stuttgart · New York
2016, 27, A–E
letter
A
M. Adib et al.
Letter
Synlett
Reaction between 4-Nitro-1,3-diarylbutan-1-ones and Ammoni-
um Acetate in the Presence of Morpholine and Sulfur: An Efficient
Synthesis of 2,4-Diarylpyrroles
Mehdi Adib*a
Neda Ayashia
Fatemeh Heidaria
Peiman Mirzaeib
Ar'
NO2
O
S8, morpholine
NH4OAc
+
Ar
80 °C, 30 min
Ar
Ar'
N
H
15 examples
89 98% yield
a School of Chemistry, College of Science, University of
Tehran, P. O. Box 14155-6455, Tehran, Iran
madib@khayam.ut.ac.ir
b Department of Chemistry, Shahid Beheshti University,
Tehran, Iran
Received: 10.12.2015
Accepted after revision: 01.03.2016
Published online: 30.03.2016
drogenation of α-phenyl-β-benzoylpropionitrile, cycliza-
tion to dihydropyrrole and then selenium-promoted oxida-
tion to 2,4-diarylpyrrole,6 dehydrogenation of 2,4-diaryl-2-
pyrrolines with selenium, Raney nickel, and nickel-support-
ed on pumice,7 N-heterocyclic carbene (NHC)-catalyzed
formylation of chalcones by C–C bond cleavage of carbohy-
drates via a retrobenzoin-type process followed by treat-
ment with NH4OAc under microwave irradiation,8 cyclocon-
densation of enones with aminoacetonitrile followed by
microwave-induced dehydrocyanation,9 rhodium-catalyzed
hydroformylation of β-alkynylamines with the synthesis
gas,10 copper-catalyzed denitrogenative annulation of vinyl
azides with aryl acetaldehydes,11 condensation of methyl
aryl ketoximes in the presence of EtMgBr and formation of
3,5-diaryloxazines followed by rearrangement in concen-
trated HI,12 a four-step sequence including iodoazidation of
an alkene followed by dehydrohalogenation, azirine forma-
tion, and carbanion induced pyrrole formation,13 and re-
duction of phenacyl azides induced by SmI2.14
Synthetic routes reported for the preparation of substi-
tuted pyrroles starting from γ-nitroketones involve: con-
densation with MeOH upon treatment with KOH/MeOH
and then H2SO4/MeOH to form 1-keto-4-dimethylacetals
followed by the acetal deprotection and condensation with
NH4OAc15 and selenium-catalyzed reaction with carbon
monoxide.16
Some of these synthetic approaches suffer from disad-
vantages such as multistep procedures, harsh reaction con-
ditions, or high pressures needed for reactions involving
gaseous reagents such as H2 or CO.
DOI: 10.1055/s-0035-1561852; Art ID: st-2015-d0957-l
Abstract An efficient synthesis of 2,4-diarylpyrroles is described.
Heating a mixture of a 4-nitro-1,3-diarylbutan-1-one and ammonium
acetate in the presence of morpholine and sulfur afforded the corre-
sponding 2,4-diarylpyrroles in excellent yields.
Key words 2,4-diarylpyrroles, 4-nitro-1,3-diarylbutan-1-ones, mor-
pholine, sulfur, heterocycles, cyclization
Heterocycles are a pervasive class of compounds found
in abundance in polymers, pharmaceutical agents, natural
products such as alkaloids, and also various synthetic or-
ganic and inorganic compounds. Pyrroles are a subcategory
of this massive group which are considered important re-
garding biological properties and chemical activities.1,2
Some classical approaches for the synthesis of pyrrole
derivatives include the Knorr reaction between α-aminoke-
tones and compounds containing a methylene group α to a
carbonyl group, the Paal–Knorr reaction between 1,4-dike-
tones and primary amines, the Hantzsch reaction between
β-ketoesters with ammonia or primary amines and also nu-
merous other synthetic routes that still being developed for
the preparation of pyrrole derivatives.3
Synthetic routes towards substituted pyrroles involve
cyclization of acyclic precursors or substitution on an exist-
ing ring. Since the modification of pyrroles by the electro-
philic aromatic substitution reactions or metal-assisted re-
actions preferably leads to the formation of α-substituted
pyrroles, the introduction of substituents into the β-posi-
tion of pyrrole is of interest.3,4 Particularly, synthetic ap-
proaches to 2,4-diaryl pyrroles especially with two differ-
ent aryl substituents are still limited. These include: zircon-
ocene-mediated reaction between primary amines,
unactivated alkynes, and carbon monoxide,5 catalytic hy-
Reaction between γ-nitro-β-arylbutyrophenones with
an ammonia source was first reported in the 1940s by Rog-
ers which led to 3,5-diaryl-1H-pyrrol-2-yl-3,5-diarylpyrrol-
2-ylideneamines (tetraarylazadipyrromethenes) as deep-
blue-colored products7,17 and then by others for the prepa-
ration of photosensitizers for photodynamic therapy and
© Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 27, A–E

B
M. Adib et al.
Letter
Synlett
Ph
Ph
Ph
Ph
Ph
NO2
O
N
O
solvent-free
80 °C, 1 h
NH4OAc
S8
+
+
+
Ph
Ph
NH
N
Ph
N
N
H
H
1a
2, 15%
3a, 40%
Scheme 1 Treatment of 4-nitro-1,3-diphenylbutan-1-one (1a) with ammonium acetate in the presence of sulfur and morpholine
synthesis of thiophene-substituted aza-BODIPYs and inves-
tigation of their optical and electrochemical properties.18 In
the course of our studies on heterocyclic compounds,19 we
performed the reaction between 4-nitro-1,3-diphenylbu-
tan-1-one (1a) and ammonium acetate by adding sulfur
and morpholine to the reaction medium. The reaction was
carried out by 1:1:1:1 molar ratios of the four compounds
at 80 °C for one hour under solvent-free conditions. TLC
monitoring of the reaction mixture exhibited formation of
the corresponding blue-colored tetraphenylazadipyr-
romethene (2) in 15% yield, in addition to a new product in
40% yield. This new product was separated by column chro-
matography. NMR spectroscopy and comparison of its
melting point with those of authentic sample reported in
the literature indicated that it was 2,4-diphenylpyrrole (3a)
and no sulfur or morpholine were contributed in its struc-
ture (Scheme 1). When this reaction was performed by
omitting sulfur or morpholine, only tetraphenylazadipyr-
romethene (2) was obtained, thus presence of both sulfur
and morpholine is crucial for the formation of 2,4-dia-
rylpyrroles 3.
In order to improve the yield of 2,4-diphenylpyrrole
(3a), influence of various affecting factors include the molar
ratio of 1a, sulfur, the amine, and NH4OAc and also reaction
temperature, reaction time, type of amines used as well as
solvents were examined for this model reaction. At first, the
reaction was carried out with different equivalents of the
reactants by the use of morpholine under solvent-free con-
ditions (Table 1, entries 1–6). According to the obtained
data the yield of 3a was significantly improved when the
amount of sulfur, morpholine, and NH4OAc were increased.
The best result was obtained with a 1:3:3:6 molar ratios,
respectively, with which 3a was obtained in 98% yield at
80 °C after 30 minutes (Table 1, entry 6). With this opti-
mized conditions in hand, next we sought to examine the
type of amines used during the reaction. Thus, the reaction
was carried out by use of some other amines such proline,
pipyridine, diethylamine, and triethylamine. With the ter-
tiary amine (triethylamine), TLC monitoring of the reaction
mixture did not show formation of 3a at 80 °C after two
hours (Table 1, entry 10). However, with the secondary
amines the results were acceptable and no significant
change on the yield of 3a was observed (Table 1, entries 7–
9). A brief evaluation of some solvents such as toluene, eth-
anol, and DMF under reflux conditions (Table 1, entries 11–
13) showed that the neat conditions was the most suitable
one. Thus a 1:3:3:6 molar ratio, morpholine as the base, re-
action temperature of 80 °C, and reaction time of 30 min
were obtained as the optimized conditions for the model
reaction (Table 1, entry 6).
Table 1 Optimization of the Reaction Conditions for the Synthesis of
3a
Entry Amine
1a/S/ Amine/ Solvent Temp
Time Yield of 3a
NH4OAc
(°C)
(h)
(%)
1
2
morpholine
1:1:1:1
1:1:1:2
1:1:1:3
1:1:1:6
1:2:2:6
1:3:3:6
1:3:3:6
1:3:3:6
1:3:3:6
1:3:3:6
1:3:3:6
1:3:3:6
1:3:3:6
–
–
–
–
–
–
–
–
–
–
80
1
1
1
1
1
40
morpholine
morpholine
morpholine
morpholine
morpholine
proline
80
80
42
58
63
90
98
98
95
93
–
3
4
80
5
80
6
80
0.5
7
100
80
2
8
pipyridine
0.5
0.5
2
9
diethylamine
triethylamine
morpholine
morpholine
morpholine
80
10
11
12
13
80
toluene reflux
4
40
42
37
EtOH
DMF
reflux
reflux
4
4
In order to elucidate the generality and scope of this
new protocol, various 4-nitro-1,3-diarylbutan-1-ones were
used for the preparation of the corresponding 2,4-dia-
rylpyrroles. Thus, a mixture of a 4-nitro-1,3-diarylbutan-1-
one 1, NH4OAc, morpholine, and sulfur was stirred at 80 °C
for 30 minutes to afford the corresponding 2,4-diarylpyr-
roles 3a–o in 89–98% yields. TLC and NMR spectroscopic
analysis of the reaction mixtures confirmed the formation
of the corresponding 2,4-diarylpyrroles 3 in excellent
yields.20 The results are summarized in Table 2.
The structures of the isolated products were deduced on
1
the basis of their IR, H NMR, and 13C NMR spectroscopy,
mass spectrometry, and comparison with those of authen-
tic samples reported in the literature.20 The IR spectrum of
3j showed a stretching band for the NH bond at 3437 cm–1.
The mass spectrum of 3j displayed the molecular ion [M+]
peak at m/z = 263, which was 67 mass units [HNO2 + H2O +
H2] less than that of the 1:1 adduct of 3-(4-methoxyphe-
nyl)-1-(4-methylphenyl)-4-nitro-1-butanone and ammo-
© Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 27, A–E

C
M. Adib et al.
Letter
Synlett
Table 2 Synthesis of 2,4-Diarylpyrroles 3a–o
Ar'
NO2
Ar'
O
S8, morpholine
80 °C, 30 min
+
NH4OAc
Ar
Ar
N
H
1
3
Entry
Ar
Ph
Ar′
Product 3
Mp (°C)
Lit. mp.
Yield (%)a
1
2
Ph
3a
3b
3c
3d
3e
3f
176–177
199
(174–176)6
(200–201)11
(145–147)16
(190–191)15
(191–192)11
(214–215)11
(215–218)15
(210–211)11
(214–216)14
98
94
92
93
89
97
96
92
95
91
94
90
92
95
93
Ph
4-MeC6H4
3-MeC6H4
4-MeOC6H4
4-FC6H4
4-ClC6H4
4-BrC6H4
Ph
3
Ph
140–141
189–190
187–189
210–212
220–222
207–209
206–208
179–181
201–202
182
4
Ph
5
Ph
6
Ph
7
Ph
3g
3h
3i
8
4-MeC6H4
4-MeC6H4
4-MeC6H4
4-MeOC6H4
4-FC6H4
4-FC6H4
4-ClC6H4
4-BrC6H4
9
4-MeC6H4
4-MeOC6H4
Ph
10
11
12
13
14
15
3j
3k
3l
(206–208)15
(176–178)15
(193–194)11
(193–194)11
(203–204)11
Ph
4-MeC6H4
Ph
3m
3n
3o
185–187
193
Ph
201–203
a Isolated yields.
nia. The 1H NMR spectrum of 3j exhibited four singlets due
to the methyl (δ = 2.29 ppm), methoxy (δ = 3.75 ppm), and
two CH units in the pyrrole ring (δ = 6.81 and 7.19 ppm).
Four characteristic doublets with appropriate chemical
shifts and coupling constants were observed in the aromat-
ic region of the spectrum for the eight H atoms of the two
para-disubstituted aryl rings as well as a fairly broad singlet
at δ = 11.27 ppm arising from the NH of pyrrole ring. The
1H-decoupled 13C NMR spectrum of 3j showed characteris-
tic signals at δ = 21.2 ppm for methyl, δ = 55.5 ppm due to
methoxy, two fairly shielded signals at δ = 102.9 and 115.7
ppm for C3H and C5H of the pyrrole ring, respectively, at δ =
124.9 ppm for C4 as well as a fairly deshielded signal at δ =
135.1 ppm for C2 of pyrrole. Eight other signals (4 × CH and
4 × C) with appropriate chemical shifts were observed for
the two para-disubstituted aryl rings in agreement with
the structure.20
A possible explanation for the formation of 2,4-di-
arylpyrroles is provided in Scheme 2. At first, γ-nitro-β-ar-
ylbutyrophenone 1 may tautomerize with the aid of mor-
pholine to form the corresponding nitronic acid 4. This acid
form may undergo nucleophilic attack of the polysulfide
morpholinium ion pair 5, generated in situ from the nucleo-
philic addition of morpholine to sulfur, to give the adduct
intermediate 6. This adduct may undergo an intramolecular
cyclisation via nucleophilic attack of the hydroxyl group to
the adjacent polysulfide moiety to give the N-hydroxyoxati-
azetidine intermediate 8 by removal of 7. A ‘SO’ fragment
may be removed21 from 8 to give oxime 9. Condensation re-
action between ammonium acetate and the carbonyl func-
tionality of 9 may lead to the formation of enamine 10,
which can be cyclized via nucleophilic attack of the amine
moiety on the imine bond to give the dihydropyrrole inter-
mediate 11, from which a hydroxyl amine may be removed
to afford 2,4-diarylpyrrole 3.
In summary, we have disclosed a novel and efficient
synthesis of 2,4-diarylpyrroles by reaction between γ-ni-
tro-β-arylbutyrophenones and ammonium acetate pro-
moted by morpholine and sulfur. The availability of the
starting materials, short reaction times, high yields of the
products, fairly mild reaction conditions, and easy workup
are the main advantages of this reaction. We believe this
experimentally simple approach could be a useful addition
to the syntheses that have been reported to date.
Acknowledgement
This research was supported by the Research Council of University of
Tehran.
© Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 27, A–E

D
M. Adib et al.
Letter
Synlett
O
O
S8
+
+
N
H
NH
O
_
S
S7
N
O
5
OH
S7
S
OH
N
O
O
S
+
O
NO2
Ar'
N
N
_
O
O
O
OH
O
OH
morpholine
5
N
S6
7
Ar
Ar
Ar
O
Ar'
Ar
Ar'
Ar
Ar'
– SO
HS
1
4
6
8
OH
N
H
Ar'
Ar'
NOH
Ar'
NH
NH
H
N
O
NH4OAc
– NH OH
Ar
Ar
Ar'
Ar
NHOH
2
N
N
H
H
9
10
11
3
Scheme 2 Proposed mechanism for the formation of 2,4-diarylpyrroles 3
References and Notes
(18) (a) Gorman, A.; Killoran, J.; O’Shea, C.; Kenna, T.; Gallagher, W.
M.; O’Shea, D. F. J. Am. Chem. Soc. 2004, 126, 10619. (b) Gresser,
R.; Hartmann, H.; Wrackmeyer, M.; Leo, K.; Riede, M. Tetrahe-
dron 2011, 67, 7148. (c) Grossi, M.; Palma, A.; McDonnell, S. O.;
Hall, M. J.; Rai, D. K.; Muldoon, J.; O’Shea, D. F. J. Org. Chem.
2012, 77, 9304.
(1) Gribble, G. W. In Comprehensive Heterocyclic Chemistry II;
Katritzky, A. R.; Rees, C. W.; Scriven, E. F. V., Eds.; Pergamon
Press: London, 1996, Vol. 2 Chap. 4,: 207–257; and references
cited therein.
(2) d’Ischia, M.; Napolitano, A.; Pezzella, A. In Comprehensive Het-
erocyclic Chemistry III; Vol. 3; Katritzky, A. R.; Ramsden, C. A.;
Scriven, E. F. V.; Taylor, R. J. K., Eds.; Chap. 4; Elsevier Science:
Oxford, 2008, 353–386; and references cited therein.
(3) (a) Bergman, J.; Janosik, T. In Comprehensive Heterocyclic Chem-
istry III; Vol. 3; Katritzky, A. R.; Ramsden, C. A.; Scriven, E. F. V.;
Taylor, R. J. K., Eds.; Chap. 3; Elsevier Science: Oxford, 2008,
269–350; and references cited therein. (b) Gilchrist, T. L. Hetero-
cyclic Chemistry; Prentice Hall: Englewood Cliffs, 1997, 3rd ed.
(4) (a) Rao, H. S. P.; Jothilingama, S.; Scheeren, H. W. Tetrahedron
2004, 60, 1625. (b) Qu, S.; Dang, Y.; Song, G.; Wen, M.; Huang, K.
W.; Wang, Z. X. J. Am. Chem. Soc. 2014, 136, 4974. (c) Srimani,
D.; Ben-David, Y.; Milstein, D. Angew. Chem. Int. Ed. 2013, 52,
4012. (d) Lavallo, V.; Frey, G. D.; Donnadieu, B.; Soleilhavoup,
M.; Bertrand, G. Angew. Chem. Int. Ed. 2008, 47, 5224.
(5) Buchwald, S. L.; Woods Wannamaker, M.; Watson, B. T. J. Am.
Chem. Soc. 1989, 111, 776.
(6) Allen, C. F. H..; Wilson, C. V. Org. Synth., Coll. Vol. III 1955, 358.
(7) Rogers, J. J. Chem. Soc. 1943, 590.
(8) Zhang, J.; Xing, C.; Tiwari, B.; Chi, Y. R. J. Am. Chem. Soc. 2013,
135, 8113.
(9) Kucukdisli, M.; Ferenc, D.; Heinz, M.; Wiebe, C.; Opatz, T. Beil-
stein J. Org. Chem. 2014, 10, 466.
(10) Campi, E. M.; Jackson, W. R.; Nilsson, Y. Tetrahedron Lett. 1991,
32, 1093.
(19) (a) Adib, M.; Janatian Ghazvini, H.; Soheilizad, M.; Saeedi, S.;
Tajbakhsh, M.; Amanlou, M. Helv. Chim. Acta 2015, 98, 1079.
(b) Adib, M.; Soheilizad, M.; Rajai-Daryasarei, S.; Mirzaei, P.
Synlett 2015, 26, 1101. (c) Sayahi, M. H.; Adib, M.; Hamooleh, Z.;
Zhu, L. G.; Amanlou, M. Helv. Chim. Acta 2015, 98, 1231. (d) Adib,
M.; Soheilizad, M.; Zhu, L. G.; Wu, J. Synlett 2015, 26, 177.
(e) Adib, M.; Bayanati, M.; Soheilizad, M.; Janatian Ghazvini, H.;
Tajbakhsh, M.; Amanlou, M. Synlett 2014, 25, 2918.
(f) Mahernia, S.; Mahdavi, M.; Adib, M. Synlett 2014, 25, 1299.
(g) Adib, M.; Sheikhi, E.; Haghshenas, P.; Rajai-Daryasarei, S.;
Bijanzadeh, H. R.; Zhu, L. G. Tetrahedron Lett. 2014, 55, 4983.
(20) General Procedure for the Preparation of 2,4-Diarylpyrroles
3a–o, Exemplified with 3a
A mixture of 4-nitro-1,3-diphenylbutan-1-one (1a, 1 mmol),
sulfur (3 mmol), morpholine (3 mmol), and NH4OAc (6 mmol)
within a 5 mL round-bottomed flask was magnetically stirred in
a silicone oil bath at 80 °C for 30 min. Progress of the reaction
was followed by TLC monitoring. Then the reaction mixture was
cooled to ambient temperature, H2O (2.5 mL) was added, and
the product was extracted into CH2Cl2 (2 × 2.5 mL). The organic
layer was dried over Na2SO4, filtered, the solvent was removed,
and the residue was purified by crystallization from EtOAc.
2,4-Diphenyl-1H-pyrrole (3a)
Colorless crystals, mp 176–177 °C, yield 0.214 g, 98%. IR (KBr):
3435 (NH), 1598, 1481, 1451, 1411, 1258, 1185, 1157, 1129,
1075, 1030, 903, 807, 746, 688 cm–1 1H NMR (300.1 MHz,
.
(11) Chen, F.; Shen, T.; Cui, Y.; Jiao, N. Org. Lett. 2012, 14, 4926.
(12) Deady, L. W. Tetrahedron 1967, 23, 3505.
(13) Zhao, W.; Carreira, E. M. Chem. Eur. J. 2006, 12, 7254.
(14) (a) Fan, X.; Zhang, X.; Zhang, Y. J. Chem. Res. 2005, 750. (b) Fan,
X.; Zhang, Y. Tetrahedron Lett. 2002, 43, 1863.
(15) Hall, M. J.; McDonnell, S. O.; Killoran, J.; O’Shea, D. F. J. Org.
Chem. 2005, 70, 5571.
(16) Umeda, R.; Mashino, T.; Nishiyama, Y. Tetrahedron 2014, 70,
4395.
DMSO-d6):  = 6.96 (1 H, s, CH), 7.13 (1 H, t, J = 7.5 Hz, CH), 7.18
(1 H, t, J = 7.5 Hz, CH), 7.32 (2 H, t, J = 7.5 Hz, 2 × CH), 7.35 (1 H,
s, CH), 7.37 (2 H, t, J = 7.6 Hz, 2 × CH), 7.61 (2 H, d, J = 7.5 Hz, 2 ×
CH), 7.69 (2 H, d, J = 7.5 Hz, 2 × CH), 11.45 (1 H, br s, NH). 13C
NMR (75.5 MHz, DMSO-d6):  = 103.7 (C3H), 117.1 (C5H), 123.9
(2 × CH), 124.9 (2 × CH), 125.2 (C4), 125.5 and 126.2 (2 × CH),
129.0 (2 × CH), 129.2 (2 × CH), 132.7 and 133.1 (2 × C) 136.2
(C2). MS: m/z (%) = 219 (100) [M+], 191 (37), 165 (15), 115 (38),
110 (13), 102 (10), 95 (6), 89 (11), 77 (10), 63 (10), 51 (11).
(17) Rogers, M. A. T. Nature (London, U.K.) 1943, 151, 504.
© Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 27, A–E

E
M. Adib et al.
Letter
Synlett
HRMS (ES+): m/z calcd for C16H14N [M + H]+: 220.1126; found:
220.1124.
4-(3-Methylphenyl)-2-phenyl-1H-pyrrole (3c)
7.61 (2 H, d, J = 7.8 Hz, 2 × CH), 11.39 (1 H, br s, NH). 13C NMR
(75.5 MHz, DMSO-d6):  = 21.2 (CH3), 103.1 (C3H), 116.6 (C5H),
123.8 (2 × CH), 124.8 (2 × CH), 125.0 (C4), 125.4 (CH), 129.0 (2 ×
CH), 129.7 (2 × CH), 130.4, 132.8, 135.3 and 136.2 (3 × C and C2).
MS: m/z (%) = 233 (100) [M+], 217 (25), 202 (21), 189 (21), 178
(8), 165 (9), 128 (8), 115 (43), 102 (12), 89 (15), 77 (16), 63 (11),
51 (11). HRMS (ES+): m/z calcd for C17H16N [M + H]+: 234.1283;
found: 234.1278.
4-(4-Methoxyphenyl)-2-(4-methylphenyl)-1H-pyrrole (3j)
Colorless crystals, mp 179–181 °C, yield 0.239 g, 91%. IR (KBr):
3437 (NH), 1610, 1581, 1533, 1500, 1439, 1297, 1238, 1177,
1130, 1033, 1032, 923, 829, 793, 716, 631 cm–1. 1H NMR (300.1
MHz, DMSO-d6):  = 2.30 (3 H, s, CH3), 3.75 (3 H, s, OCH3), 6.81
(1 H, s, CH), 6.90 (2 H, d, J = 8.7 Hz, 2 × CH), 7.18 (2 H, d, J = 8.1
Hz, 2 × CH), 7.19 (1 H, s, CH), 7.51 (2 H, d, J = 8.7 Hz, 2 × CH),
7.56 (2 H, d, J = 8.1 Hz, 2 × CH), 11.27 (1 H, br s, CH). 13C NMR
(75.5 MHz, DMSO-d6):  = 21.2 (CH3), 55.5 (OCH3), 102.9 (C3H),
114.4 (2 × CH), 115.7 (C5H), 123.8 (2 × CH), 124.9 (C4), 126.0 (2 ×
CH), 129.0 (C), 129.7 (2 × CH), 130.5 and 132.6 (2 × C), 135.1
(C2), 157.5 (CO). MS: m/z (%) = 263 (100) [M+], 248 (90), 220
(12), 204 (12), 178 (14), 165 (7), 152 (6), 132 (10), 119 (23), 102
(6), 91 (17), 77 (10), 65 (7).
Colorless crystals, mp 140–141 °C, yield 0.214 g, 92%. IR (KBr):
3401 (NH), 1597, 1479, 1451, 1413, 1265, 1225, 1188, 1130,
1038, 929, 898, 760, 688 cm–1. 1H NMR (300.1 MHz, DMSO-d6):
 = 2.34 (3 H, s, CH3), 6.95 (1 H, d, J = 7.5 Hz, CH), 6.97 (1 H, s,
CH), 7.19 (1 H, t, J = 7.8 Hz, CH), 7.21(1 H, dd, J = 8.1, 7.8 Hz, CH),
7.33 (1 H, s, CH), 7.36 (1 H, d, J = 7.5 Hz, CH), 7.40 (2 H, t, J = 7.5
Hz, 2 × CH), 7.46 (1 H, s, CH), 7.69 (2 H, d, J = 7.8 Hz, 2 × CH),
11.45 (1 H, br s, NH). 13C NMR (75.5 MHz, DMSO-d6):  = 21.7
(CH3), 103.7 (C3H), 117.0 (C5H), 122.1 (CH), 123.8 (2 × CH), 125.2
(C4), 125.5, 126.1, 126.2 and 128.9 (4 × CH), 129.2 (2 × CH),
132.6, 133.1, 136.0 and 137.9 (3 × C and C2). MS: m/z (%) = 233
(100) [M+], 217 (17), 202 (13), 189 (15), 165 (7), 129 (11), 115
(25), 102 (10), 89 (8), 77 (13), 63 (7), 51 (8). HRMS (ES+): m/z
calcd for C17H16N [M + H]+: 234.1283; found: 234.1291.
2-(4-Methylphenyl)-4-phenyl-1H-pyrrole (3h)
Colorless crystals, mp 207–209 °C, yield 0.214 g, 92%. IR (KBr):
3385 (NH), 1598, 1532, 1491, 1442, 1259, 1212, 1184, 1132,
1078, 1033, 922, 802, 747, 688 cm–1 1H NMR (300.1 MHz,
.
DMSO-d6):  = 2.30 (3 H, s, CH3), 6.90 (1 H, s, CH), 7.12 (1 H, t,
J = 7.5 Hz, CH), 7.19 (2 H, d, J = 7.8 Hz, 2 × CH), 7.31 (1 H, s, CH),
7.32 (2 H, t, J = 7.5 Hz, 2 × CH), 7.58 (2 H, d, J = 7.5 Hz, 2 × CH),
(21) Nguyen, T. B.; Pasturaud, K.; Ermolenko, L.; Al-Mourabit, A. Org.
Lett. 2015, 17, 2562.
© Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 27, A–E