Reaction of arylglyoxals with pyrrole or indole in aqueous media: Facile synthesis of heteroaryl α-acyloins

Article abstract of DOI:10.1007/s13738-013-0362-x

Pyrrole or indole reacts with arylglyoxal monohydrates in aqueous media in the absence of any catalyst to produce pyrrol-2-yl or indol-3-yl α-acyloin derivatives in high yields as the only product. Reactions were clean and products were isolated by simple filtration. When the reactions were carried out in acetonitrile as solvent, different products were obtained.

Full text of DOI:10.1007/s13738-013-0362-x

J IRAN CHEM SOC (2014) 11:963–968
DOI 10.1007/s13738-013-0362-x
ORIGINAL PAPER
Reaction of arylglyoxals with pyrrole or indole in aqueous
media: facile synthesis of heteroaryl a-acyloins
•
Mohammad Anary-Abbasinejad
Mahdiyeh Talebizadeh
Received: 30 June 2013 / Accepted: 25 September 2013 / Published online: 10 October 2013
Ó Iranian Chemical Society 2013
Abstract Pyrrole or indole reacts with arylglyoxal
monohydrates in aqueous media in the absence of any
catalyst to produce pyrrol-2-yl or indol-3-yl a-acyloin
derivatives in high yields as the only product. Reactions
were clean and products were isolated by simple filtration.
When the reactions were carried out in acetonitrile as
solvent, different products were obtained.
processes both in industry and laboratory [9–13]. Water
also shows novel reactivity and selectivity for synthesis of
chemically important and biologically active compounds in
industry [14–17].
The electrophilic substitution reactions of indole and
pyrrole have been extensively studied [18]. It is well-
known that the reaction of indole with electrophiles almost
always occurs on the C-3 position. In contrast, pyrrole
usually reacts with electrophiles at C-2 position faster than
C-3 position, although the electrophilic substitution on C-3
position is also observed. Aromatic aldehydes have been
reported to react with two equivalents of indole or pyrrole
in acidic media to produce diindolyl or dipyrrolylarylm-
thanes [19–22]. Although numerous methods have been
reported for the reaction of indole with aromatic or ali-
phatic aldehydes or ketones and many acidic catalysts have
been reported to affect these reactions, there are only a few
reports on similar reaction between indole and arylglyoxals
to produce diindolylethanones [23]. When neutral media is
used, this reaction is occurred with 1:1 mol ratio between
indole and arylglyoxals leading to heteroaryl a-acyloins
[24]. Although the reaction between N-substituted pyrroles
and arylglyoxals in neutral conditions has been reported to
afford the related acyloins [24], the reaction of pyrrole
itself with glyoxals has been reported to afford mixtures of
mono- and di-substituted pyrrole derivatives [25]. The
above mentioned reactions between indole or pyrrole
derivatives and arylglyoxals for synthesis of heteroaryl a-
acyloins have been done in boiling benzene as solvent,
which is highly toxic, and moderate yields of products have
been obtained. Indol-3-yl a-acyloins have also been
reported as non-isolated intermediates, produced by the
reaction between arylglyoxals and indole, which react with
enaminones to afford functionalized pyrroles [26]. Here we
wish to report that pyrrole or indole react with arylglyoxals
Keywords Indole ꢀ Arylglyoxals ꢀ Electrophilic
substitution ꢀ Benzoins
Introduction
Indole and pyrrole are among the most important chemical
skeletons existing as the main core in the structure of
various physiologically, pharmaceutically, and industrially
important compounds [1–5]. For example indole deriva-
tives involve beneficial estron metabolism promoter [1],
inhibitor for human prostate cancer cells [2] and radical
scavengers [3]. The importance of pyrrole containing nat-
ural products, such as heme, chlorophyl and vitamin B12
has stimulated extensive studies on the synthesis and
chemical behavior of pyrrole derivatives [6].
Using water as solvent for chemical reactions has
attracted much interests from chemists in recent years,
because it offers a powerful tool for minimizing waste
production and harmful organic solvent dispersal [7, 8].
Being naturally abundant, readily available and environ-
mentally benign makes water an ideal solvent for chemical
M. Anary-Abbasinejad (&) ꢀ M. Talebizadeh
Department of Chemistry, Vali-e-Asr University,
77176 Rafsanjan, Iran
e-mail: m.anary@vru.ac.ir
123

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J IRAN CHEM SOC (2014) 11:963–968
in aqueous media in the absence of any catalyst to produce
pyrrol-2-yl or indol-3-yl a-acyloin derivatives in high
yields as the only product. Reactions are clean and pro-
ducts are isolated as pure compounds by simple filtration.
100 MHz): d = 71.0 (C–OH), 111.4, 118.8, 119.2, 121.2,
124.5, 124.6, 125.0, 125.7, 126.2, 127.1, 127.3, 128.3,
129.9, 131.7, 133.3, 134.4, 135.9, 136.1, 202.6 (C=O).
2-hydroxy-2-(1H-indol-3-yl)-1-phenylethanone
(3b):
Yield: 95 %; white powder; m.p.174–177 °C. IR (KBr)
(tmax, cm-1): 3,412 and 3,313 (NH and OH), 1,657 (C=O).
Calcd. for (C16H13NO2): C, 76.48; H, 5.21; N, 5.57 %.
Experimental procedures
1
Found: C, 76.7; H, 5.1; N, 5.3 %. H NMR (d6-DMSO,
Materials and characterization techniques
400 MHz): d = 5.50 (1 H, braod s, OH), 6.37 (1 H, s, O–
CH), 6.98 (1 H, t 3JHH = 8 Hz), 7.06 (1 H, t 3JHH = 8 Hz),
7.34 (2 H, m), 7.40 (2 H, m), 7.51 (1 H, m), 7.63 (1 H, d
3JHH = 8 Hz), 8.00 (2 H, m), 11.07 (1 H, s, NH). 13C NMR
(d6-DMSO, 100 MHz): d = 69.3 (C–OH), 111.5, 113.2,
118.8, 119.1, 121.2, 124.68, 124.8, 125.5, 128.4, 132.8,
134.9, 136.2 (aromatic carbons), 198.9 (C=O).
All the utilized arylglyoxals were prepared by the SeO2-
oxidation of the related aryl methyl ketones on the basis of
the reported procedure and used as their monohydrates
[27]. All melting points are uncorrected. Elemental anal-
yses were performed using a Heraeus CHN-O-Rapid ana-
lyzer. IR spectra were recorded on a Shimadzu IR-470
2-hydroxy-2-(1H-indol-3-yl)-1-(p-tolyl)ethanone (3c):
Yield: 89 %; white powder; m.p.154–158 °C. IR (KBr)
(tmax, cm-1): 3,415 and 3,309 (NH and OH), 1,654 (C=O).
Calcd. for (C17H15NO2): C, 76.96; H, 5.70; N, 5.28 %.
1
spectrometer. H and 13C NMR spectra were recorded on
Bruker DRX-400 Avance spectrometer at 400 and
100 MHz, respectively. 1H and 13C NMR spectra were
obtained on solution in d6-DMSO using TMS as internal
standard. The chemicals used in this work purchased from
Fluka (Buchs, Switzerland) and were used without further
purification. Structure of compounds 3d, 3e, 6c, 6e and 6f
were proved by comparing their physical and spectral data
with the previously reported data. The other products were
characterized using NMR and IR spectral and analytical
data.
1
Found: C, 76.7; H, 5.8; N, 5.5 %. H NMR (d6-DMSO,
400 MHz): d = 2.28 (3 H, s, CH3), 5.46 (1 H, d
3
3JHH = 5 Hz, OH), 6.32 (1 H, d JHH = 5 Hz, O–CH),
3
6.97 (1 H, m), 7.05 (1 H, m), 7.20 (2 H, d JHH = 8 Hz),
3
7.32 (1 H, m), 7.61 (1H, d JHH = 8 Hz), 7.90 (2 H, d
3JHH = 8 Hz), 11.04 (1 H, s, NH). 13C NMR (d6-DMSO,
100 MHz): d = 21.0 (CH3), 69.0 (C–OH), 111.5, 118.8,
119.1, 121.2, 124.6, 124.7, 125.5, 128.5, 128.9, 132.3,
136.2, 143.2 (aromatic carbons), 198.5 (C=O).
General procedure for synthesis of compounds 3a–e and
5a–d: A mixture of indole (2 mol, for preparation of 3a–e)
or pyrrole (2 mmol, for preparation of 5a–d) and arylgly-
oxal monohydrate (2 mol) in water was stirred at room
temperature for 5 h. The solid was filtered off and washed
with diethyl ether (20 mL) to afford the pure product.
General procedure for synthesis of compounds 6a–f and
7a–c: A mixture of indole (4 mol, for preparation of 6a–f))
or pyrrole (1 mmol, for preparation of 7a–c) and arylgly-
oxal monohydrate (2 mol) in acetonitrile was stirred at
room temperature for 5 h. The solvent was evaporated
under reduced pressure and the solid was washed with
diethyl ether to give the pure product.
2-hydroxy-2-(1H-indol-3-yl)-1-(4-chlorophenyl)ethanone
(3d) [24]: Yield: 97 %; white powder; m.p. 144–146 °C. 1H
NMR (d6-DMSO, 400 MHz): d = 5.65 (1 H, d 3JHH = 5 Hz,
3
OH), 6.36 (1 H, d JHH = 5 Hz, O–CH), 6.99 (1 H, t
3
3JHH = 8 Hz,), 7.06 (1 H, t JHH = 8 Hz), 7.31 (1 H, d
3JHH = 8 Hz), 7.34 (1 H, s,), 7.44 (2 H, d 3JHH = 8 Hz), 7.60
(1 H, d 3JHH = 8 Hz), 8.10 (2 H, d 3JHH = 8 Hz), 11.07 (1 H,
s, NH).
2-hydroxy-2-(1H-indol-3-yl)-1-(4-bromophenyl)ethanone
(3e) [24]: Yield: 95 %; white powder; m.p. 159–161 °C. 1H
NMR (d6-DMSO, 400 MHz): d = 5.63 (1 H, d 3JHH = 5 Hz,
3
OH), 6.32 (1 H, d JHH = 5 Hz, O–CH), 6.96 (1 H, t
3
3JHH = 8 Hz), 7.11 (1 H, t JHH = 8 Hz), 7.32 (1 H, d
Selected spectral data:
3JHH = 8 Hz), 7.35 (1 H, d, 8 Hz), 7.37 (1 H, s,), 7.60 (2 H, d
3JHH = 8 Hz), 8.01 (2 H, d 3JHH = 8 Hz), 11.08 (1 H, s, NH).
2-hydroxy-2-(1H-pyrrol-2-yl)-1-(naphthalene-1-yl)etha-
none (5a): Yield: 95 %; white powder; m.p.106–108 °C.
IR (KBr) (tmax, cm-1): 3,460 and 3,349 (NH and OH),
1,667 (C=O). Calcd. for (C16H13NO2): C, 76.48; H, 5.21;
N, 5.57 %. Found: C, 76.6; H, 5.3; N, 5.6 %. 1H NMR (d6-
2-hydroxy-2-(1H-indol-3-yl)-1-(naphthalene-1-yl)ethanone
(3a): Yield: 90 %; white powder; m.p.177–182 °C. IR
(KBr) (tmax, cm-1): 3,415 and 3,309 (NH and OH), 1,654
(C=O). Calcd. for (C20H15NO2): C, 79.72; H, 5.02; N,
1
4.65 %. Found: C, 79.7; H, 5.1; N,4.5 %. H NMR (d6-
3
DMSO, 400 MHz): 5.68 (1 H, d JHH = 5 Hz, OH), 6.43
3
DMSO, 400 MHz): 5.76 (1 H, d JHH = 5 Hz, OH), 5.81
(2 H, m), 6.1 (1 H, d 3JHH = 5 Hz, O–CH), 6.60 (1 H, m),
(1 H, d 3JHH = 5 Hz, O–CH), 6.98 (2 H, m), 7.25 (2 H, m),
2
7.49 (2 H, m), 7.68(1 H, d JHH = 8 Hz), 7.90 (1H, m),
3
7.57 (4 H, m), 7.96 (2 H, m), 8.00 (1 H, d JHH = 8 Hz),
8.00 (1H, d 3JHH = 8 Hz), 8.11 (1H, d 3JHH = 8 Hz), 8.20
(1H, m), 10.96 (1 H, s, NH). 13C NMR (d6-DMSO,
8.26 (1 H, m), 10.87 (1 H, s, NH). 13C NMR (d6-DMSO,
100 MHz): d = 71.2 (C–OH), 106.7, 107.6, 118.2, 124.5,
123

J IRAN CHEM SOC (2014) 11:963–968
965
125.0, 126.3, 127.1, 127.5, 128.0, 128.3, 129.8, 131.9,
133.2, 134.3 (aromatic carbons), 201.3 (C=O).
(tmax, cm-1): 3,407 (NH), 1,672 (C=O). Calcd. for
(C28H20N2O): C, 83.98; H, 5.03; N, 7.00 %. Found: C, 83.9;
H, 5.2; N, 7.3 %. 1H NMR (DMSO, 400 MHz): d = 6.85 (1
2-hydroxy-2-(1H-pyrrol-2-yl)-1-(naphthalene-2-yl)etha-
none (5b): Yield: 90 %; white powder; m.p.115–117 °C.
IR (KBr) (tmax, cm-1): 3,727 and 3,399 (NH and OH),
1,678 (C=O). Calcd. for (C16H13NO2): C, 76.48; H, 5.21;
N, 5.57 %. Found: C, 76.7; H, 5.2; N, 5.7 %. 1H NMR (d6-
3
H, s, CH), 6.95 (2 H, t, JHH = 8 Hz), 7.05 (2 H, t,
3
3JHH = 8 Hz), 7.24 (2 H, m), 7.34 (2 H, d, JHH = 8 Hz),
7.62 (4 H, m), 7.95 (2 H, m), 8.12 (2 H, m), 8.99 (1 H, s), 10.94
(2 H, NH): 13C NMR (d6-DMSO, 100 MHz): d = 41.4 (CH),
111.4, 112.9, 118.4, 119.0, 120.9, 124.4, 124.4, 126.4, 126.8,
127.5, 128.1, 128.5, 129.5, 129.9, 132.1, 133.7, 134.8, 136.2
(aromatic carbons), 197.8 (C=O).
3
DMSO, 400 MHz): 5.74 (1 H, d JHH = 5 Hz, OH), 5.89
(1 H, m), 6.24 (1 H, d 3JHH = 5 Hz, O–CH), 6.68 (1 H, m),
7.58 (2 H, m), 7.77–8.11 (5 H, m), 8.69 (1 H, s), 10.94 (1
H, s, NH). 13C NMR (d6-DMSO, 100 MHz): d = 69.5 (C–
OH), 107.0, 107.6, 118.2, 124.1, 126.9, 127.5, 128.1,
128.5, 129.1, 129.5, 130.2, 131.9, 132.0, 134.8, 197.5
(C=O).
2,2-di(1H-indol-3-yl)-1-phenylethanone (6c) [23]: Yield:
1
90 %; white powder; m.p. 205–207 °C. H NMR (DMSO,
3
400 MHz): d = 6.64 (1 H, s), 6.93 (2 H, t JHH = 7 Hz),
7.04 (2 H, t JHH = 7 Hz), 7.17 (2 H, s), 7.33 (2 H, d
3
3
2-hydroxy-2-(1H-pyrrol-2-yl)-1-(phenyl)ethanone (5c):
Yield: 95 %; white powder; m.p.123–125 °C. IR (KBr)
(tmax, cm-1): 3,727 and 3,420 (NH and OH), 1,682 (C=O).
Calcd. for (C12H11NO2): C, 71.63; H, 5.51; N, 6.96 %.
Found: C, 71.7; H, 5.4; N, 7.1 %. 1H NMR (DMSO,
400 MHZ): 5.64 (1 H, d 3JHH = 6 Hz, OH), 5.89 (2 H, m),
6.05 (1 H, d 3JHH = 6 Hz, O–CH), 6.68 (1 H, s), 7.45 (2 H,
3JHH = 8 Hz), 7.46 (2 H, d JHH = 7 Hz), 7.55 (3 H, d
3
3JHH = 3 Hz), 8.16 (2 H, d JHH = 8 Hz), 10.91 (2 H, 2
NH).
2,2-di(1H-indol-3-yl)-1-(p-tolyl)ethanone (6d): Yield:
90 %; white powder; m.p. 255–257 °C. IR (KBr) (tmax
,
cm-1): 3,399 (NH), 1,674(C=O). Calcd. for (C25H20N2O):
C, 82.39; H, 5.53; N, 7.69 %. Found: C, 82.5; H, 5.4; N,
7.6 %. 1H NMR (d6-DMSO, 400 MHz): d = 2.32 (3 H, s,
CH3),6.63 (1 H, s), 6.94 (2 H, t 3JHH = 8 Hz,), 7.05 (2 H,
3
m), 7.57 (1 H, m), 7.96 (2 H, d JHH = 7 Hz), 10.89 (1 H,
s, NH). 13C NMR (DMSO, 100 MHz): d = 69.5 (C–OH),
106.9, 107.5, 118.1, 118.2, 128.5, 133.0, 134.7 (aromatic
carbons), 197.6 (C=O).
t
3JHH = 8 Hz), 7.17 (2 H, m), 7.27 (2 H, d,
3
3JHH = 8 Hz), 7.34 (2 H, d, JHH = 8 Hz,), 7.56 (2 H, d,
3
2-hydroxy-2-(1H-pyrrol-2-yl)-1-(p-tolyl)ethanone (5d):
Yield: 89 %; white powder; m.p.126–128 °C. IR (KBr)
(tmax, cm-1): 3,726 and 3,388 (NH and OH), 1,679 (C=O).
Calcd. for (C13H13NO2): C, 72.54; H, 6.09; N, 6.51 %.
3JHH = 8 Hz), 8.08 (2 H, d JHH = 8 Hz), 10.92 (2 H, 2
NH). 13C NMR (d6-DMSO, 100 MHz): d = 21.0 (CH3),
41.3, 111.4, 113.0, 118.4, 118.9, 120.9, 124.3, 126.4,
128.6, 129.1, 134.0, 136.2, 143.1 (aromatic carbons),
197.4 (C=O).
1
Found: C, 72.7; H, 6.0; N, 6.3 %. H NMR (d6-DMSO,
400 MHz): d = 2.37 (3 H, s, CH3), 5.57 (1 H, d
3JHH = 5 Hz, OH), 5.81 (1 H, m), 5.87 (1 H, m), 6.03 (1H,
2,2-di(1H-indol-3-yl)-1-(4-chlorophenyl)ethanone (6e)
1
[23]: Yield: 95 %; white powder; m.p. 195–197 °C. H
d
3JHH = 5 Hz, O–CH), 6.66 (1 H, m), 7.26 (2 H, d,
NMR (DMSO, 400 MHz): d = 6.58 (1 H, s), 6.93 (2 H, t
3
3
3JHH = 8 Hz), 7.86 (2 H, d, JHH = 8 Hz), 10.86 (1 H, s,
NH). 13C NMR (d6-DMSO, 100 MHz): d = 21.1 (CH3),
69.2 (C–OH), 96.3, 106.8, 107.5, 118.1, 128.6, 129.0,
132.1, 143.4 (aromatic carbons), 197.1 (C=O).
3JHH = 7 Hz), 7.04 (2 H, t JHH = 7 Hz), 7.15 (2 H, d
3
3JHH = 2 Hz), 7.35 (2 H, d JHH = 8 Hz), 7.52 (2 H, d
3
3JHH = 8 Hz), 7.57 (2 H, d JHH = 8 Hz), 8.15 (2 H, d
3JHH = 8 Hz), 10.97 (2 H, 2 NH).
2,2-di(1H-indol-3-yl)-1-(naphthalene-1-yl)ethanone (6a):
2,2-di(1H-indol-3-yl)-1-(4-bromophenyl)ethanone (6f)
1
Yield: 90 %; white powder; m.p.234–239 °C. IR (KBr) (tmax
,
[23]: Yield: 90 %; white powder; m.p. 229–230 °C. H
cm-1): 3,411 (NH), 1,654(C=O). Calcd. for (C28H20N2O): C,
83.98; H, 5.03; N, 7.00 %. Found: C, 83.7; H, 5.0; N, 7.2 %.
1H NMR (d6-DMSO, 400 MHz): d = 6.66 (1 H, s), 6.96 (2 H,
t3JHH = 8 Hz),7.05(2H,t3JHH = 8 Hz),7.26(2H, m), 7.33
NMR (DMSO, 400 MHz): d = 6.35 (1 H, s), 6.87 (2 H, s),
6.95 (2 H, t 3JHH = 7 Hz), 7.09 (2 H, t 3JHH = 7 Hz), 7.25
3
3
(2 H, d JHH = 8 Hz), 7.40 (2 H, d JHH = 8 Hz), 7.45 (2
H, d 3JHH = 8 Hz), 7.86 (2 H, d 3JHH = 8 Hz), 10.20 (2 H,
2 NH).
3
(2 H, d JHH = 8 Hz), 7.49 (2 H, m), 7.58 (1 H, t
3JHH = 8 Hz), 7.66 (2 H, d 3JHH = 8 Hz), 7.94 (1 H, m), 8.05
2,20-(1H-pyrrole-2,5-diyl)bis[2-hydroxy-1-(naphthalene-
1-yl)]ethanone (7a): 85 %; white powder; m.p. 100–105 °C.
IR (KBr) (tmax, cm-1): 3,623 and 3,343 (NH and OH), 1,617
(C=O). Calcd. for (C28H21NO4): C, 77.23; H, 4.86; N,
3.22; %. Found: C, 77.4; H, 5.1; N, 3.1 %. Major isomer
3
(1H, d JHH = 8 Hz), 8.28 (1 H, m), 8.43 (1 H, d
3JHH = 8 Hz), 10.92 (2 H, 2 NH). 13C NM (d6-DMSO,
100 MHz): d = 44.8 (CH), 111.4, 112.5, 118.4, 118.9,
121.0, 124.3, 124.7, 125.3, 126.2, 126.6, 126.9, 127.3, 128.3,
130.1, 131.8, 133.4, 136.2, 136.4 (aromatic carbons), 201.2
(C=O).
1
(55 %) H NMR (d6-DMSO, 400 MHz): d = 5.60 (2 H, d
3JHH = 4 Hz, 2 OH), 5.77 (2 H, m)*, 6.03 (2 H, d
3
2,2-di(1H-indol-3-yl)-1-(naphthalene-2-yl)ethanone (6b):
Yield: 93 %; white powder; m.p. 268–270 °C. IR (KBr)
3JHH = 5 Hz), 7.36 (2 H, t JHH = 8 Hz), 7.52 (4 H, m)*,
3
7.75 (2 H, d JHH = 8 Hz), 7.94 (2 H, m), 8.18 (2 H, m),
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J IRAN CHEM SOC (2014) 11:963–968
10.91 (1 H, NH). 13C NMR (d6-DMSO, 100 MHz): d = 71.6
(O–CH), 107.6, 124.9, 125.5, 126.8, 127.8, 128.0, 128.8*,
129.5, 130.3, 132.4, 133.7, 134.5* (aromatic carbons), 201.6
(C=O)*. Minor isomer (45 %): 1H NMR (d6-DMSO,
400 MHz): d = 5.64 (2 H, d 3JHH = 4 Hz, 2 OH), 5.77 (2 H,
m)*, 6.13 (2 H, d 3JHH = 5 Hz), 7.44 (2 H, t 3JHH = 8 Hz),
7.52 (4 H, m)*, 7.83 (2 H, d 3JHH = 8 Hz), 8.03 (2 H,m), 8.22
(2 H, m), 11.02 (1 H, NH). 13C NMR (d6-DMSO, 100 MHz):
71.5 (O–CH), 107.6, 124.9, 125.5, 126.7, 127.6, 127.9,
128.8*, 129.6, 130.2, 132.4, 133.7, 134.5* (aromatic car-
bons), 201.6 (C=O)*.
O
HO
O
Ar
H2O
OH
+
Ar
r.t. 5 h
N
N
OH
H
H
2
3
1
yield%*
90
Ar
3
a
1-naphthyl
95
89
b
c
Ph
4-MeC6H4
4-ClC6H4
4-BrC6H4
2,20-(1H-pyrrole-2,5-diyl)bis[2-hydroxy-1-(naphthalene-
2-yl)]ethanone (7b): 90 %; white powder; m.p.127 °C. IR
(KBr) (tmax, cm-1): 3,623 and 3,357 (NH and OH), 1,676
(C=O). Calcd. for (C28H21NO4): C, 77.23; H, 4.86; N,
3.22 %. Found: C, 77.4; H, 5.0; N, 3.3 %. Major isomer
d
e
97
95
*Isolated yields
Scheme 1 Reaction between indole and arylglyoxals in water
1
(60 %) H NMR (d6-DMSO, 400 MHz): d = 5.72 (2 H,
3
m)*, 5.75 (2 H, d JHH = 6 Hz, 2 OH), 6.18 (2 H, d
deduced from IR and NMR spectral and analytical data.
The 1H NMR spectrum of 3a exhibited two doublets
(3JHH = 5 Hz) at 5.68 and 6.43 ppm, respectively, for OH
and O–CH protons. The NH proton resonated at
10.96 ppm as a broad single signal. The aromatic protons
resonated between 6.98 and 8.20 ppm. When the spec-
trum was prepared after addition of a few drops of D2O to
d6-DMSO solution of compound 3a, the signals related to
the OH and NH protons were disappeared and the signal
related to the O–CH proton converted to a single signal,
showing the spin–spin coupling between OH and O–CH
protons. 13C NMR spectrum of 3a shows twenty distinct
signals consistent with the proposed structure, the methine
(O–CH) and carbonyl carbons resonating at 71.0 and
202.6 ppm, respectively. The structure of compound 3a
was also confirmed by its IR spectrum, which exhibited
two absorption bands at 3,415 and 3,309 cm-1 for NH and
OH bonds and an absorption band at 1,654 cm-1 for the
carbonyl group. This reaction was also examined between
indole and other arylglyoxals and as shown in Scheme 1
the expected benzoin derivatives were obtained in excel-
lent yields.
3JHH = 6 Hz, 2 O–CH)), 7.50–8.20 (6 H, m)*, 8.57 (2 H, s),
11.16 (1 H, NH). 13C NMR (d6-DMSO, 100 MHz):
d = 69.2 (O–CH), 107.4, 123.6*, 124.0, 126.8, 127.5,
128.0, 128.8, 129.4, 130.2*, 131.8, 131.9*, 134.8 (aromatic
carbons), 197.1 (C=O). Minor isomer (40 %): d = 5.72 (2
3
H, m)*, 5.77 (2 H, d JHH = 6 Hz, 2 OH), 6.23 (2 H, d
3JHH = 6 Hz, 2 O–CH)), 7.50 - 8.20 (6 H, m)*, 8.62 (2 H,
s), 11.26 (1 H, NH). 13C NMR (d6-DMSO, 100 MHz):
d = 69.5, 107.4, 123.6*, 124.1, 126.7, 127.5, 127.9, 128.5,
129.4, 130.2*, 131.7, 131.9*, 134.7 (aromatic carbons),
197.3 (C=O).
2,20-(1H-pyrrole-2,5-diyl)bis[2-hydroxy-1-(p-tolyl)]eth-
anone (7c): Yield: 87 %; white powder; m.p.79–80 °C. IR
(KBr) (tmax, cm-1): 3,407 and 3,370 (NH and OH), 1,676
(C=O). Calcd. for (C22H21NO4): C, 72.71; H, 5.82; N,
3.85 %. Found: C, 72.4; H, 5.7; N, 3.9 %. Major isomer
(66 %): 1H NMR (d6-DMSO, 400 MHz): d = 2.33 (6 H, s,
3
CH3), 5.60 (2 H, d JHH = 5 Hz, 2 OH), 5.67 (2 H, m,)*,
3
5.97 (2 H, d JHH = 5 Hz, 2 O–CH), 7.19 (4 H, d
3
3JHH = 8 Hz), 7.78 (4 H, d JHH = 8 Hz,), 10.97 (1 H,
NH). Minor isomer (34 %): 1H NMR (d6-DMSO,
400 MHz): d = 2.23 (6 H, s, CH3), 5.63 (2 H, d
3JHH = 5 Hz, 2 OH), 5.67 (2 H, m,)*, 6.00 (2 H, d
We also examined similar reaction between pyrrole and
arylglyoxals in aqueous media. As shown in Scheme 2, the
reaction is compatible for pyrrole as for indole and excel-
lent yields of pyrrol-2-yl a-acyloin derivatives 5a–d were
obtained in good yields.
3
3JHH = 5 Hz, 2 O–CH), 7.25 (4 H, d JHH = 8 Hz), 7.84
3
(4 H, d JHH = 8 Hz,), 11.03 (1 H, NH).
*For two isomers
The reaction of indole or pyrrole was also examined
with more reactive dehydrated arylglyoxals in water, but no
improvement in reaction time or yield of products was
observed and the related benzoins were isolated in high
yields. However, no reaction was observed between indole
or pyrrole and general aldehydes such as 4-bromobenzal-
dehyde or even electron-deficient 4-nitrobenzaldehyde in
water in the obscene of any catalyst and starting materials
were isolated after 24 h stirring at room temperature.
Results and discussion
To investigate the reaction between arylglyoxals and
indole, at first a mixture of 1-naphthyl glyoxal monohy-
drate and indole in water was stirred at room temperature
for 5 h (Scheme 1). Then the product was filtered off and
washed with diethyl ether. The structure of product 3a was
123

J IRAN CHEM SOC (2014) 11:963–968
967
Ar
O
Ar
O
Ar
CH3CN
r.t. 5 h
H2O
OH
OH
OH
O
O
O
+
2
+
Ar
Ar
N
N
r.t. 5 h
N
HO
N
H
OH
H
OH
H
OH
H
2
7
4
2
5
4
yield%*
Ar
7
*
5
a
b
c
Ar
yield%
1-naphthyl
2-naphthyl
4-MeC6H4
a
b
c
85
90
1-naphthyl
2-naphthyl
95
90
87
*Isolated yields
Ph
95
89
4-MeC6H4
d
Scheme 4 Reaction between pyrrole and arylglyoxals in acetonitrile
*
Isolated yields
diastereomers. The NMR spectra of 7a show the existence of
both isomers. The 1H NMR spectrum of compound 7a
exhibited two double signals (3JHH = 5 Hz) at 5.60 and
6.03 ppm for OH and O–CH protons of the major isomer (the
corresponding signals for the minor isomer were observed as
two doublets at 5.64 and 6.13 ppm). Two broad single signals
were observed at 10.91 and 11.02 ppm for the NH protons of
two isomers. When the spectrum was prepared after addition
of a few drops of D2O to d6-DMSO solution of compound 7a,
the signals related to the OH and NH protons were disap-
peared and the signal related to the O–CH protons converted
to single signals. 13C NMR spectrum of compound 7a
exhibited two sets of 14 distinct signals for two isomers in
consistent with the proposed structure. As shown in
Scheme 4 the reaction of pyrrole was also examined with
2-naphthylglyoxal and 4-methyl phenyl glyoxal in acetoni-
trile and the corresponding 2,5-disubstituted pyrrole deriva-
tives 7b and 7c were obtained in good yields both of them as
two diastereomers.
Scheme 2 Reaction between pyrrole and arylglyoxals in water
H
N
O
Ar
O
CH3CN
r.t. 5 h
OH
OH
+
Ar
2
N
N
H
H
2
6
1
yield%*
6
Ar
1-naphthyl
a
90
93
b
2-naphthyl
c
d
Ph
90
90
4-MeC6H4
e
f
4-ClC6H4
4-BrC6H4
95
90
*
Isolated yields
Scheme 3 Reaction between indole and arylglyoxals in acetonitrile
Conclusions
To explore the role of water as the solvent of reaction
between indole or pyrrole and arylglyoxals, the above reac-
tions were investigated in acetonitrile as solvent. When indole
was reacted with 1-naphthylglyoxal hydrate in acetonitrile,
after 5 h stirring at room temperature, evaporating the solvent
and washingthe residue withdiethyl ether a puresolidproduct
was obtained. The analytical and NMR spectral data showed
that the product is 2,2-bis(indol-3-yl)-1-(1-naphthyl)ethanone
6a (Scheme 3). We could not isolate any traces of compound
3a from this reaction. The reaction was also examined with
other arylglyoxal hydrates and good yields of the corre-
sponding 2,2-bis(indol-3-yl)-1-(aryl)ethanone derivatives
were obtained (Scheme 3).
In summary, we report herein that the reaction between
indole or pyrrole with arylglyoxals in aqueous media pro-
vides a facile and efficient route for synthesis of indol-3-yl
or pyrrol-2-yl a-acyloins in good yields. The advantages of
the method are readily available starting materials, neutral
reaction conditions, using water as an environmentally
green solvent and simple isolation and purification of
products. The reaction of indole with arylglyoxals in ace-
tonitrile as solvent afforded bis(indolyl) arylethanones in
good yields. Reaction between pyrrole and arylglyoxals in
acetonitrile afforded disubstituted pyrrole derivatives.
When pyrrole was reacted with arylglyoxals in acetoni-
trile, different products were obtained. For example, from the
reaction between pyrrole and 1-naphthylglyoxal in acetoni-
trile at room temperature, compound 7a was isolated as the
only product in 85 % yield (Scheme 4). Compound 7a pos-
sesses two stereogenic centers and may exist as two
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