An eco-friendly procedure for the efficient synthesis of bis(indolyl)methanes in aqueous media

Article abstract of DOI:10.1016/j.jorganchem.2009.05.004

A new, convenient and high yielding procedure for the preparation of bis(indolyl)methanes in water by electrophilic substitution reaction of indoles with different carbonyl compounds in the presence of a catalytic amount of [Cu(3,4-tmtppa)](MeSO₄

Full text of DOI:10.1016/j.jorganchem.2009.05.004

Journal of Organometallic Chemistry 694 (2009) 3027–3031
Contents lists available at ScienceDirect
Journal of Organometallic Chemistry
journal homepage: www.elsevier.com/locate/jorganchem
An eco-friendly procedure for the efficient synthesis of bis(indolyl)methanes
in aqueous media
a,*
b
c
a
Sara Sobhani , Elham Safaei , Ali-Reza Hasaninejad , Soodabeh Rezazadeh
a
Department of Chemistry, College of Sciences, Birjand University, Shovkat abad, Birjand 414, Iran
Institute for Advanced Studies in Basic Sciences (IASBS), Zanjan 45195, Iran
Department of Chemistry, Faculty of Sciences, Persian Gulf University, Bushehr 75169, Iran
b
c
a r t i c l e i n f o
a b s t r a c t
Article history:
A new, convenient and high yielding procedure for the preparation of bis(indolyl)methanes in water by
electrophilic substitution reaction of indoles with different carbonyl compounds in the presence of a
catalytic amount of [Cu(3,4-tmtppa)](MeSO ) (1 mol%) as a highly stable and reusable catalyst is
4 4
described. This procedure has also been applied successfully for the preparation of bis(pyrazole-5-ols)
and dipyrromethanes.
Received 22 January 2009
Received in revised form 28 April 2009
Accepted 7 May 2009
Available online 13 May 2009
Ó 2009 Elsevier B.V. All rights reserved.
Keywords:
Bis(indolyl)methanes
Aldehydes
Ketones
Aqueous media
1
. Introduction
Use of aqueous media as a reaction solvent has attracted much
in the presence of protic [13] or Lewis acids [14–16]. However,
these procedures suffer from certain limitations when acid sensi-
tive substrates are used. On the other hand, many Lewis acids
are deactivated or some times decomposed by nitrogen-containing
reactants. Even when the desired reactions proceed, more than
stoichiometric amounts of Lewis acids are required. Many at-
tempts have been done by organic chemists to circumvent this
problem [17–22]. However, most of the reported methods suffer
from one or more of the following drawbacks: using large amounts
of solid supports or un-recyclable catalysts which would eventu-
ally result in the generation of a large amount of toxic waste, long
reaction times, moderate yields of the products, amenable only for
aldehydes as carbonyl compounds and requiring an additional
microwave or ultrasound irradiation. Therefore, it is necessary to
further develop an efficient and convenient method for the synthe-
sis of such significant scaffolds.
attention in synthetic organic chemistry for several reasons [1,2].
In comparison with organic solvents, water is cheap, safe and re-
duces the use of harmful organic solvents and leads to the develop-
ment of environmentally friendly chemical processes [3]. In
addition, reactions in aqueous media illustrate unique reactivities
and selectivities that are not usually observed in organic media
[
4–6]. However, organic solvents are still used instead of water
for mainly two reasons. First, most organic substrates are not sol-
uble in water and as a result, water cannot function as a reaction
medium. Second, many reactive substrates, reagents and catalysts
are sensitive towards water and are decomposed or deactivated in
aqueous media. Therefore, efforts to carry out organic reactions in
water pose an important challenge in the area of reaction design.
Indole derivatives are known for their vast applications in mate-
rial sciences [7], agrochemicals [8] and pharmaceuticals [9,10].
Among these compounds, the substrates including bis(indo-
lyl)methane moieties, such as secondary metabolites [11] and mar-
ine-sponge alkaloids [12], are important classes of bioactive
metabolites. Thus, the synthesis of bis(indolyl)methanes has re-
ceived an increasing attention in recent years. The simple method
for the synthesis of this class of compounds involves the electro-
philic substitution reaction of indoles with carbonyl compounds
Metallophthalocyanines (Mpc), which are structurally similar to
metal porphyrins, are easily accessible, more stable to degradation
and cost effective than porphyrins. They have been extensively used
as efficient catalysts in a variety of organic reactions [23–29]. Tetra-
pyridinoporphyrazines (tppa) are heterocyclic phthalocyanine (pc)
derivatives in which benzene rings are replaced with electron-with-
drawing pyridine rings. The presence of pyridine rings in these com-
pounds not only increases the reactivity of tppa compared with pc,
but also allows the facile quaternarization processes. The
0
00
000
N,N ,N ,N -tetramethylated quaternized form of tetrapyridinopor-
phyrazine can be prepared easily by its reaction with dimethyl
sulfate in dimethyl formamide [30]. The resulting tetramethyl-
*
Corresponding author. Tel.: +98 561 2502008; fax: +98 561 2502009.
E-mail addresses: ssobhani@birjand.ac.ir, sobhanisara@yahoo.com (S. Sobhani).
0
022-328X/$ - see front matter Ó 2009 Elsevier B.V. All rights reserved.
doi:10.1016/j.jorganchem.2009.05.004

3
028
S. Sobhani et al. / Journal of Organometallic Chemistry 694 (2009) 3027–3031
Me
Table 1
MeSO4-+N
Synthesis of bis(indolyl)methanes (5–7) by electrophilic substitution reaction of
indoles (2–4) with carbonyl compounds catalyzed by [Cu(3,4-tmtppa)](MeSO in
water at 90 °C.
4 4
)
Entry
R1
R2
Indole
Product
Time (h)
Yielda (%)
N
N
N
N
1
2
3
4
5
6
7
8
9
C
C
C
6
6
6
H
H
H
5
5
5
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
2
3
4
2
2
2
2
2
2
2
2
2
2
2
2
2
2
5a
6a
7a
5b
5c
5d
5e
5f
5g
5h
5i
5j
5k
5l
5m
5n
5o
5p
5q
5r
5s
2
1.5
2
0.5
0.75
2
0.5
0.25
1
1.5
1.25
2.5
2
3
3
92
94
90
97
96
90
90
95
92
90
80
94
90
71
75
90
92
70
74
80
84
Me
N+
MeSO4-
Cu
N
N
N+
MeSO4-
4-O
2-O N–C H
2-Cl–C
4-Cl–C
2,6-Cl
4-Me–C
4-MeO–C
6 5
C H CH@CH
2-Thienyl
2-Furyl
3-Indolyl
C
n-Pentyl
n-Hexyl
4-OHC-C
–(CH
–(CH ) –
Me
N–C
H
2
6
4
4
Me
2
6
N
N
6
H
H
4
4
6
2 6 3
–C H
N+ MeSO4-
Me
6
H
4
10
6
H
4
11
1
14
1
1
17
2
Fig. 1. [Cu(3,4-tmtppa)](MeSO
)
4 4
(1).
5
6
H
6 5
CHMe
tetra-3,4-pyridinoporphyrazinato copper(II) methyl sulfate
Cu(3,4-tmtppa)](MeSO (1) (Fig. 1) is a water soluble compound
and has considerable low solubility in common organic solvents.
Unlike for metallophthalocyanine, the reports on catalytic activity
of metallotetrapyridinoporphyrazine in organic reactions are rare
in the literature [31–33].
1.5
2
2.5
1.5
2
18
19
20
[
4 4
)
b
6
H
4
2
2
)
5
–
2
2
2
21
22
2
4
CO
2
Me
0.5
a
Yields refer to those of pure isolated products characterized by spectral data.
Conditions: indole/terephetaldehyde: 4/1.
In continuation of our ongoing interest on the discovery of new
b
applications of [Cu(3,4-tmtppa)](MeSO
transformations, we have recently reported efficient synthesis of
-aminophosphonates in the presence of [Cu(3,4-tmtppa)](Me-
SO [34].
Herein, we report successful application of [Cu(3,4-tmtppa)]-
MeSO as a recyclable catalyst for the synthesis of various types
4 4
) as a catalyst in organic
1
tron-donating and electron-withdrawing groups underwent
electrophilic substitution reaction with indole 2, and gave the
corresponding bis(indolyl)methanes in 90–97% yields (Entries
4–10). Acid-sensitive aldehydes, such as cinnamaldehyde, thio-
phene-2-carbaldehyde, furfural and indol-3-carbaldehyde under-
went smooth reactions without any decomposition or
polymerization under the present reaction conditions producing
the corresponding bis(indolyl)methanes in 71–94% yields (Entries
4 4
)
(
4 4
)
of bis(indolyl)methanes by electrophilic substitution reaction of
indoles with aldehydes and ketones in water.
2
. Results and discussion
1
1–15). Moreover, aliphatic aldehydes were all effective substrates
to successfully execute the electrophilic substitution reaction with
indole catalyzed by [Cu(3,4-tmtppa)](MeSO (Entries 16–18).
The electrophilic substitution reaction of indole and benzalde-
hyde in water with different catalytic amounts of [Cu(3,4-
tmtppa)](MeSO and at different reaction temperatures have
investigated in order to optimize the reaction conditions. The best
yield of the corresponding bis(indolyl)methane was obtained in
4 4
)
Tetrakis-indolyl methane (5p) was also prepared successfully by
the presented method in good yield from terephthaldehyde (Entry
19). In addition to aldehydes, some ketones were also screened to
carry out the electrophilic substitution reaction by [Cu(3,4-
4
)
4
4 4
the presence of 1 mol% of [Cu(3,4-tmtppa)](MeSO ) and at 90 °C.
To show the generality and scope of this synthetic method, the
electrophilic substitution reaction of indoles (2–4) with different
carbonyl compounds was studied in the presence of [Cu(3,4-
4 4
tmtppa)](MeSO ) in aqueous media. The results showed that the
reactions involved acyclic dialkyl ketones and cyclic ketones
worked well and the expected products could be smoothly
achieved in 74–84% yields (Entries 20–22). However, no product
was obtained when aryl ketones such as benzophenone and aceto-
phenone were involved in this reaction under the same conditions.
tmtppa)](MeSO
Scheme 1, Table 1).
As shown in Table 1, the catalytic electrophilic substitution
4 4
) in water, using optimized reaction conditions
(
reaction of benzaldehyde proceeded well with different substi-
tuted indoles (Entries 1–3). Substituted benzaldehydes with elec-
4 4
The ability to recycle and reuse of [Cu(3,4-tmtppa)](MeSO ) (1)
was studied in this system. For this purpose, after performing the
R1
R2
R4
O
R4
+
2
[
Cu(3,4-tmtppa)](MeSO4)4
1 mol%)
(
R3
R3
°
R1
R2
H2O, 90 C
70-98%
N
N
H
H
R1 = aryl, alkyl, heteroaryl
R2 = H, alkyl
2: R ,R4 = H
3
5: R ,R4 = H
6: R3 = Me, R4 = H
7: R3 = H, R4 = Br
3
3: R3 = Me, R4 = H
: R3 = H, R4 = Br
4
Scheme 1.

S. Sobhani et al. / Journal of Organometallic Chemistry 694 (2009) 3027–3031
3029
preparation reaction of bis(indolyl)methane 5a under the condi-
Ph
[
4 4
Cu(3,4-tmtppa)](MeSO ) (1)
tions described in Table 1, the reaction mixture was washed with
ethyl acetate. The separated aqueous layer containing the catalyst
was re-used for a consecutive run under the same reaction condi-
tions. The average isolated yield for ten consecutive runs was
Ar-H + PhCHO
-15
H
2
O
Ar
Ar
8
Scheme 2.
8
8.7%, which clearly demonstrates the practical reusability of this
catalyst (Fig. 2). This reusability demonstrates the high stability
and turnover of [Cu(3,4-tmtppa)](MeSO under the employed
Table 3
4 4
)
Results of the reaction of electron-rich aromatic compounds with benzaldehyde in the
presence of catalyst 1.
conditions. It is worth to note that the recyclability test was
stopped after ten runs.
Entry
1
Electron-rich aromatic compound
Time (h)
0.5
Yielda (%)
95b
The effect of reaction media on the electrophilic substitution
reaction of indole 2a with benzaldehyde catalyzed by 1 was also
studied (Table 2). A survey of solvents revealed that the reaction
media had a significant effect on this process. The results showed
that the use of water as reaction media was superior to the others.
In this solvent the highest yield of the desired product (5a) was ob-
tained after shorter reaction time (Table 2, Entry 1). Under the
same reaction conditions, when one equivalent of indole was used,
the desired product (5a) was obtained in lower yields (Table 2, En-
try 2).
N
N
O
Ph
8
2
3
4
5
6
7
8
Pyrrole (9)
0.5
24
24
24
24
24
24
70c
0
0
0
0
N,N-diethylaniline (10)
2-Methylthiophene (11)
Anisole (12)
Phenol (13)
Mesitylene (14)
p-Xylene (15)
0
0
Re-usability of the catalyst, easy work-up along with the high
yields of the products encouraged us to study the applicability of
this method for other electron-rich aromatic compounds (8–15)
a
Yields refer to those of pure isolated products. Conditions: 8–15/benzaldehyde:
/1; catalyst 1 (5 mol%, except for Entries 1 and 2); 90 °C (except for Entry 2).
2
(Scheme 2, Table 3).
b
Catalyst 1 (3 mol%).
According to Table 3, the best results were obtained when pyr-
c
Catalyst 1 (1 mol%), room temperature.
azolone (8) and pyrrole (9) were used as electron-rich aromatic
compounds. Subsequently, the reactions of pyrazolone (8) and pyr-
role (9) with a variety of aldehydes were investigated under the
same reaction conditions. The results are depicted in Table 4.
As shown in Table 4, treatment of pyrazolone (8) or pyrrole with
different aldehydes in water in the presence of [Cu(3,4-tmtppa)]-
(
MeSO
4 4
) (1) gave bis(pyrazol-5-ols) (10) and dipyrromethanes
(11) (Scheme 3) in good to high yields.
4 4
In conclusion, we have found that [Cu(3,4-tmtppa)](MeSO )
Time Yield
can be used as a new, re-usable and efficient catalyst for the prep-
aration of a variety of bis(indolyl)methanes by electrophilic substi-
tution reaction of indoles with aldehydes/ketones in water. This
reaction system not only provides a novel method for the synthesis
of bis(indolyl)methanes, but also extends the applicability of
160
140
120
100
8
0
0
0
0
4 4
[Cu(3,4-tmtppa)](MeSO ) in organic synthesis in water which
leads to environmentally friendly chemical processes. This prop-
erty combined with ease of recovery and catalyst re-usability
makes this method an economic, benign and waste-free chemical
process for the synthesis of bis(indolyl)methanes. This procedure
has also successfully applied for the preparation of bis(pyrazole-
6
4
2
0
1
2
3
4
5
6
7
8
9
10
5
-ols) and dipyrromethanes.
Fig. 2. Reusability of [Cu(3,4-tmtppa)](MeSO
bis(indolyl)methane 5a.
4 4
) as a catalyst for the preparation of
3
. Experimental
3.1. Materials and physical measurements
Table 2
Effect of reaction media on the preparation of 5a from the electrophilic substitution
reaction of indole 2a with benzaldehyde catalyzed by 1.
Chemicals were purchased from Merck and Fluka Chemical
Companies. Melting points were determined by Buchi 510 appara-
tus and are uncorrected. IR spectra were run on a Perkin–Elmer
780 instrument. NMR spectra were recorded on a Bruker Avance
DPX-250. The purity of the products and the progress of the reac-
tions were accomplished by TLC on silica-gel polygram SILG/UV254
plates.
Entry
Solvent
Waterb
Time (h)
Yielda (%)
1
2
3
4
5
6
7
8
9
2
1
92
48
45
5
30
70
75
45
30
50
b,d
Water
c
3
CH CN
24
24
24
24
24
24
24
24
b
DMSO
THFc
CH
3
OHc
c
iso-Propanol
Benzene
3
.2. Typical procedure for the synthesis of bis(indolyl)methanes (5a)
c
b
Toluene
b
Benzaldehyde (1.06 g, 10 mmol) and indole 2 (2.34 g, 20 mmol)
1
0
–
was added to a stirring solution of [Cu(3,4-tmtppa)](MeSO
4 4
)
a
Yields refer to those of pure isolated products. Conditions: 2a/benzaldehyde: 2/
(
0.108 g, 0.1 mmol) in water (20 mL). The mixture was heated in
1
(except for Entry 2); catalyst 1 (1 mol%).
b
an oil bath at 90 °C for an appropriate time (Table 1). Water
(20 mL) was added to the cooled reaction mixture. Then the reac-
tion mixture was washed with EtOAc (3 ꢀ 20 mL) and the organic
Conditions: 90 °C.
Conditions: reflux.
Conditions: 2a/benzaldehyde: 1/1.
c
d

3
030
S. Sobhani et al. / Journal of Organometallic Chemistry 694 (2009) 3027–3031
Table 4
4 4
Results of the reaction of pyrazolone (8) and pyrrole (9) with aldehydes in the presence of [Cu(3,4-tmtppa)](MeSO ) (1) in water.
Entry
R1
Electron-rich aromatic compound
Product
Time (min)
Yielda (%)
b
1
2
3
4
5
6
7
8
9
C
6
H
5
8
9
8
9
8
8
9
8
9
8
8
9
8
10a
11a
10b
11b
10d
10e
11e
10g
11g
10h
10t
30
30
5
–
5
95
70
c
b
4-O
2
N–C
6
H
4
98
b
c
98
b
2-Cl–C
4-Cl–C
6
H
H
4
90
b
6
4
60
98
b
c
–
98
b
4-Me–C
6
H
4
30
95
b
c
–
84
b
1
1
1
1
0
1
2
3
4-MeO–C
2-OH–C
4-Br–C
2-Furyl
6
H
4
45
15
93
b
6
H
4
95
b
c
6
H
4
11u
10k
–
97
b
30
90
a
Yields refer to those of pure isolated products characterized by comparison of their spectral data and physical properties with those of authentic samples [35–38].
Conditions: catalyst (3 mol%); 90 °C.
Conditions: catalyst (1 mol%); room temperature.
b
c
R1
R1
3.5. Spectral data for bis(indolyl)methanes
N
N
Compound 5a: mp 140–142 °C; IR (KBr): 3402 (N–H) cm ; 1H
NMR (CDCl , TMS): d 5.86 (s, 1 H), 6.66 (s, 2 H), 7.11 (t, 2 H,
J = 6.9 Hz), 7.14–7.22 (m, 3 H), 7.28–7.31 (m, 2 H), 7.35–7.42 (m,
-1
N
N
HN
NH
Ph
3
Ph
OH HO
1
3
6
H), 7.93 (br s, NH) ppm; C NMR (CDCl
3
, TMS): d 31.6, 110.9,
11.9, 118.4, 119.5, 121.2, 124.0, 126.3, 127.1, 128.5, 128.6,
1
0
11
1
Scheme 3.
137.0, 145.2 ppm.
Compound 5b: mp 217–219 °C; IR (KBr): 3423 (N–H) cm ; H
NMR (CDCl , TMS): d 6.01 (s, 1 H), 6.72 (s, 2 H), 7.02–7.08 (m, 4 H),
.36 (d, 2 H, J = 8.1 Hz), 7.41 (d, 2 H, J = 8.1 Hz), 7.49 (d, 2 H,
J = 8.6 Hz), 8.05 (br s, NH), 8.17 (d, 2 H, J = 8.6 Hz) ppm.
ꢁ1 1
3
7
layer was separated and washed with H
separated organic phase dried over Na SO
2
O (3 ꢀ 10 mL). Then the
2
4
and concentrated under
1
Compound 5c: mp 139–141 °C; H NMR (CDCl
H), 6.91 (s, 2 H), 7.08–7.17 (m, 4 H), 7.29 (d, 2 H, J = 7.8 Hz), 7.47
d, 2 H, J = 7.9 Hz), 7.57–7.66 (m, 2 H), 7.79–7.90 (m, 2 H), 8.21 (d, 2
H, J = 8.6 Hz) ppm.
Compound 5d: mp 74–76 °C; IR (KBr): 3412 (N–H) cm 1; 1
NMR (CDCl , TMS): d 6.32 (s, 1 H), 6.67 (s, 2 H), 7.02 (t, 2 H,
3
, TMS): d 6.12 (s,
reduced pressure to give the crude product. The crude product was
purified by chromatography on silica-gel eluted with n-hexane/
EtOAc (5/1). Separated aqueous layer containing the catalyst was
combined and concentrated to appropriate volume (20 mL) and re-
used for the preparation of bis(indolyl)methane (5a) following the
above procedure.
1
(
ꢁ
H
3
J = 7.8 Hz), 7.10–7.22 (m, 6 H), 7.38–7.43 (m, 4 H), 7.98 (br s, NH)
ppm.
3.3. Typical procedure for the synthesis of bis(pyrazole-5-ols) (10a)
Compound 5e: mp 78–80 °C; IR (KBr): 3412 (N–H) cm 1; 1
ꢁ
H
3
NMR (CDCl , TMS): d 5.86 (s, 1 H), 6.65 (s, 2 H), 6.85–7.96 (m, 12
Benzaldehyde (1.06 g, 10 mmol) and pyrazolone 8 (3.48 g,
0 mmol) was added to a stirring solution of [Cu(3,4-tmtppa)](Me-
H), 8.00 (br s, NH) ppm.
2
Compound 5f: mp 108 °C; IR (KBr): m
3440 (N–H) cm 1; 1H NMR
ꢁ
SO (0.324 g, 0.3 mmol) in water (20 mL). The mixture was
4 4
)
(
CDCl
3
, TMS): d 6.58 (s, 1 H), 6.68 (s, 2 H), 6.86–7.03 (m, 7 H), 7.09
heated in an oil bath at 90 °C for an appropriate time (Table 4).
Water (20 mL) was added to the cooled reaction mixture. Then
the reaction mixture was washed with EtOAc (3 ꢀ 20 mL) and
13
(
d, 2 H, J = 7.8 Hz), 7.41 (d, 2 H, J = 7.8 Hz), 7.71 (br s, NH) ppm;
C
3
NMR (CDCl , TMS): d 37.2, 110.7, 114.4, 119.3, 119.6, 121.4, 121.8,
1
24.7, 127.2, 128.2, 128.6, 136.3, 138.7 ppm.
Compound 5g: mp 95–97 °C; IR (KBr):
the organic layer was separated and washed with
2
H O
m H
3411 (N–H) cm 1; 1
ꢁ
(
3 ꢀ 10 mL). Then the separated organic phase dried over Na
2 4
SO
NMR (CDCl
.04 (t, 2 H, J = 7.1 Hz), 7.12 (d, 2 H, J = 7.1 Hz), 7.23–7.28 (m, 6
H), 7.41 (d, 2 H, J = 7.2 Hz), 7.94 (br s, NH) ppm.
Compound 5h: mp 186–188 °C; IR (KBr):
3410 (N–H) cm 1
H NMR (CDCl , TMS): d 3.76 (s, 3 H), 5.85, (s, 1 H), 6.68 (s, 2 H),
.91 (d, 2 H, J = 8.2 Hz), 7.02 (t, 2 H, J = 7.3 Hz), 7.16 (t, 2 H,
J = 7.3 Hz), 7.20 (m, 2 H), 7.35–7.41 (m, 4 H), 7.95 (br s, NH) ppm.
3
, TMS): d 2.33 (s, 3 H), 5.87 (s, 1 H), 6.69 (s, 2 H),
and concentrated under reduced pressure to give the crude prod-
uct. The crude product was purified by recrystallization from eth-
anol (95%).
7
ꢁ
m
;
1
3
.4. Typical procedure for the synthesis of dipyrromethane (11a)
3
6
Benzaldehyde (1.06 g, 10 mmol) and pyrrole
0 mmol) was added to a stirring solution of [Cu(3,4-tmtppa)](Me-
(0.108 g, 0.1 mmol) in water (20 mL). The mixture was stir-
9 (1.34 g,
1
Compound 5i: mp 100–102 °C; H NMR (CDCl
H), 6.19 (m, 1 H), 6.57 (d, 1 H, J = 15.4 Hz), 6.89 (s, 2 H), 7.02–7.09
m, 4 H), 7.26–7.32 (m, 7 H), 7.49 (d, 2 H, J = 7.9 Hz), 7.92 (br s, NH)
ppm.
Compound 5j: mp 147–149 °C; IR (KBr):
NMR (CDCl , TMS): d 6.08 (s, 1 H), 6.86 (s, 2 H), 6.97–7.45 (m, 11 H),
3
, TMS): d 5.22 (m,
2
1
(
4 4
SO )
red at room temperature for an appropriate time (Table 4).
Water (20 mL) was added to the reaction mixture. Then the reac-
tion mixture was washed with EtOAc (3 ꢀ 20 mL) and the organic
m
3410 (N–H) cm 1; 1H
ꢁ
layer was separated and washed with H
2
O (3 ꢀ 10 mL). Then the
3
1
3
7
.94 (br s, NH) ppm; C NMR (CDCl
3
, TMS): d 35.9, 110.3, 111.5,
separated organic phase dried over Na SO and concentrated under
2 4
1
19.3, 120.0, 121.8, 122.6, 123.5, 125.3, 126.3, 128.9, 136.7, 145.5.
reduced pressure to give the crude product. The crude product was
purified by chromatography on silica-gel eluted with n-hexane/
EtOAc (3/1).
ꢁ1
Compound 5k: mp 318–319 °C; IR (KBr):
m 3410 (N–H) cm ;
1
H NMR (CDCl , TMS): d 5.97 (s, 1 H), 6.90 (s, 2 H), 7.08–7.43 (m,
3

S. Sobhani et al. / Journal of Organometallic Chemistry 694 (2009) 3027–3031
3031
1
1
1
1 H), 8.00 (br s, NH) ppm; 13C NMR (CDCl
10.2, 111.3, 112.2, 118.0, 119.3, 119.7, 121.7, 124.3, 126.3,
35.9, 142.0 ppm.
3
, TMS): d 34.8, 106.5,
3.7. Spectral data for a selected dipyrromethane
3334 (N–H) cm 1
ꢁ
;
Compound 11a: mp 100–101 °C; IR (KBr):
H NMR (CDCl , TMS): d 5.49 (s, 1 H), 5.92 (s, 2 H), 6.14–6.18 (m, 2
3
m
3400 (N–H) cmꢁ1;
1
Compound 5l: mp 162 °C (dec.); IR (KBr):
H NMR (DMSO-d ): d 6.11 (s, 1 H), 6.86–6.91 (m, 6 H), 7.05 (m,
H), 7.35 (d, 3 H, J = 7.9 Hz), 7.52 (d, 3 H, J = 7.9 Hz), 10.59 (s, 3
m
1
13
6
H), 6.70–6.72 (m, 2 H), 7.21–7.36 (m, 5 H), 7.94 (br s, NH) ppm;
C
3
NMR (CDCl , TMS): d 43.9, 107.3, 108.4, 117.3, 126.9, 128.4, 128.7,
3
1
3
H, NH) ppm; C NMR (DMSO-d
19.1, 118.1, 117.8, 111.2, 30.8 ppm.
Compound 5m: mp 165–167 °C; 1H NMR (CDCl
6
): d 136.4, 126.6, 123.0, 120.5,
132.6, 142.1 ppm.
1
3
, TMS): d 1.37
Acknowledgments
(
d, 3 H, J = 7.0 Hz), 4.12 (m, 1 H), 4.78 (d, 1 H, J = 10.5 Hz), 6.52
(
s, 2 H), 7.04–7.17 (m, 13 H), 7.90 (br s, NH) ppm.
We are thankful to Birjand University Research Council,
Institute of Advanced Studies in Basic Sciences (IASBS) and Persian
Gulf University for their supports.
3426 (N–H) cm 1; 1
ꢁ
H
Compound 5n: mp 71–73 °C; IR (KBr):
NMR (CDCl
m
3
, TMS) d: 0.89 (t, 3 H, J = 6.7 Hz), 1.27–1.33 (m, 6 H),
1
4
.52 (m, 2 H), 4.79 (t, 1 H, J = 6.6 Hz), 6.91 (s, 2 H), 6.99–7.07 (m,
H), 7.30 (d, 2 H, J = 7.8 Hz), 7.55 (d, 2 H, J = 7.8 Hz), 7.94 (br s,
References
NH) ppm.
Compound 5o: mp 66–68 °C; IR (KBr):
NMR (CDCl , TMS): d 0.83 (t, 3 H, J = 6.8 Hz), 1.23–1.36 (m, 8 H),
.19 (m, 2 H), 4.66 (t, 1 H, J = 7.2 Hz), 7.00–7.04 (m, 4 H), 7.13 (t,
3414 (N–H) cmꢁ1; 1
H
[1] C.J. Li, T.H. Chan, Organic Reactions in Aqueous Media, John Wiley and Sons,
New York, 1997.
m
3
[
[
[
2] P.A. Grieco, Organic Synthesis in Water, Blackie Academic and Professional,
London, 1998.
3] P. Anastas, J.C. Warner, Green Chemistry: Theory and Practice, Oxford
University Press, Oxford, 1998.
2
2
7
H, J = 8.0 Hz), 7.31 (d, 2 H, J = 8.0 Hz), 7.57 (d, 2 H, J = 7.2 Hz),
.90 (br s, NH) ppm.
Compound 5p: mp 191 °C (dec.); IR (KBr):
4] D.C. Rideout, R. Breslow, J. Am. Chem. Soc. 102 (1980) 7816.
m
3405 (N–H) cmꢁ1;
[5] R. Breslow, Acc. Chem. Res. 24 (1991) 159.
6] J.B.F.N. Engberts, M. Blandamer, Chem. Commun. (2001) 1701.
[7] K.W. Lo, K.H.K. Tsang, W.K. Hui, N. Zhu, Chem. Commun. (2003) 2704.
1
[
H NMR (DMSO-d ): d 5.87 (s, 2 H), 6.54 (s, 4 H), 7.09–7.18 (m, 8 H),
.28–7.41 (m, 12 H), 8.14 (br s, NH) ppm. C NMR (CDCl , TMS): d
3
6
13
7
3
1
[
8] J.R. Plimmer, D.W. Gammon, N.N. Ragsdale, Encyclopedia of Argochemicals,
vol. 3, John Wiley and Sons, New York, 2003.
0.7, 111.8, 117.9, 118.1, 119.4, 121.1, 124.0, 126.6, 127.9, 137.0,
42.7 ppm.
[9] R.J. Sndberg, The Chemistry of Indoles, Academic Press, New York, 1970.
[10] T. Osawa, M. Namiki, Tetrahedron Lett. 24 (1983) 4719.
11] S. Zhao, X. Liao, J.M. Cook, Org. Lett. 4 (2002) 687.
Compound 5q: mp 163–165 °C; IR (KBr):
H NMR (CDCl , TMS): d 1.61 (m, 2 H), 1.69 (m, 4 H), 2.54–2.57
m
3442 (N–H) cmꢁ1;
[
[
1
3
12] B. Jiang, C.G. Yang, J.B. Wang, J. Org. Chem. 67 (2002) 1396.
(
m, 4 H), 6.91 (s, 2 H), 7.05–7.12 (m, 4 H), 7.34 (d, 2 H,
[13] W.E. Noland, M.R. Venkiteswaren, C.G. Richards, J. Org. Chem. 26 (1961) 4241.
[
[
14] G. Babu, N. Sridhar, P.T. Perumal, Synth. Commun. 30 (2000) 1609–1614.
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Soc., Perkin Trans. 1 (1980) 553.
J = 7.8 Hz), 7.58 (d, 2 H, J = 7.5 Hz), 7.94 (br s, NH) ppm.
5
r: mp 72–74 °C; IR (KBr):
m
3475 (N–H) cm 1; 1H NMR (CDCl
ꢁ
3
,
TMS): d 1.75 (m, 4 H), 2.45 (m, 4 H), 6.75 (t, 2 H, J = 8.0 Hz), 6.95 (m,
H), 7.20 (d, 2 H, J = 8.0 Hz), 7.45 (d, 2 H, J = 8.0 Hz), 7.90 (br s, NH)
ppm.
Compound 5s: mp 158 °C; IR (KBr):
[16] D.P. Chen, L.B. Yu, P.G. Wang, Tetrahedron Lett. 37 (1996) 4467.
[
[
17] R. Ghosh, S. Maiti, J. Mol. Catal. 264 (2007) 1.
18] M.A. Zolfigol, P. Salehi, M. Shiri, Z. Tanbakouchian, Catal. Commun. 8 (2007)
4
173.
m
3400 (N–H), 1721 (C@O)
, TMS): d 1.96 (s, 3 H, CO CH ), 3.47 (s, 3 H,
), 6.71 (s, 2 H), 6.76–6.82 (m, 2 H), 6.90–6.96 (m, 2 H), 7.24
d, 2 H, J = 7.5 Hz), 7.31 (d, 2 H, J = 7.5 Hz), 9.38 (br s, NH) ppm;
[19] M.M. Heravi, Kh. Bakhtiari, A. Fatehi, F.F. Bamoharram, Catal. Commun. 9
(2008) 289.
ꢁ1 1
cm
;
H NMR (CDCl
3
2
3
[
[
20] V.T. Kamble, K.R. Kadam, N.S. Joshi, D.B. Muley, Catal. Commun. 8 (2006) 498.
21] J.R. Satam, K.D. Parghi, R.V. Jayaram, Catal. Commun. 9 (2008) 1071.
CH
3
(
[22] S.V. Nadkarni, M.B. Gawande, R.V. Jayaram, J.M. Nagarkar, Catal. Commun. 9
2008) 1728.
1
3
(
C NMR (CDCl
19.8, 120.2, 122.4, 125.0, 136.0, 175.3 ppm.
Compound 6a: mp 245–247 °C; IR (KBr):
3
, TMS): d 25.0, 45.2, 51.0, 110.6, 117.7, 118.1,
[
[
23] B. Meunier, A. Sorokin, Acc. Chem. Res. 30 (1997) 470.
24] A. Sorokin, S. De Suzzoni-Dezard, D. Poullain, J.P. Noel, B. Meunier, J. Am. Chem.
Soc. 118 (1996) 7410.
1
ꢁ
m
3405 (N–H) cm 1; 1H
3
NMR (CDCl , TMS): d 2.05 (s, 6 H), 5.88 (s, 1 H), 6.78–7.01 (m, 6 H),
[25] A. Sorokin, B. Meunier, J. Chem. Soc., Chem. Commun. (1994) 1799.
[
[
[
26] G. Rajagopal, S.S. Kim, S.C. George, Appl. Organometal. Chem. 21 (2007) 198.
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28] D. Zemin, P.J. Scammells, J. Org. Chem. 72 (2007) 9881.
7
.14–7.22 (m, 5 H), 7.28–7.31 (m, 2 H), 8.02 (br s, NH) ppm.
ꢁ
Compound 7a: mp 251 °C; IR (KBr):
m
3418 (N–H) cm 1; 1
H
NMR (CDCl
H), 8.00 (br s, NH) ppm.
3
, TMS): d 5.78 (s, 1 H), 6.65 (s, 2 H), 7.20–7.29 (m, 11
[29] A.B. Sorokin, S. Mangematin, C. Pergrale, J. Mol. Catal. A: Chem. 182–183
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(
[
30] T.S. Smith, J. Iivorness, H. Taylor, J.R. Pilbrow, G.R. Sinclair, J. Chem. Soc., Dalton
Trans. 7 (1983) 1391.
3
.6. Spectral data for selected bis(pyrazole-5-ols)
[31] B. Akhlaghinia, S. Tavakoli, M. Asadi, E. Safaei, J. Porphyrins Phthalocyanines 10
2006) 167.
32] B. Akhlaghinia, M. Asadi, E. Safaei, E. Heydarpoor, Phosphorus Sulfur Silicon
79 (2004) 2099.
[33] B. Akhlaghinia, M. Asadi, E. Safaei, E. Heydarpoor, J. Porphyrins
Phthalocyanines 8 (2004) 1285.
(
[
Compound 10b: mp 219–220 °C; IR (KBr):
H NMR (DMSO-d
m
3056 (O–H) cmꢁ1;
1
1
6
, TMS): d 2.35 (s, 6 H), 5.13 (s, 1 H), 7.25–7.27
(
m, 2 H), 7.44 (t, 4 H, J = 7.0 Hz), 7.52 (d, 2 H, J = 8.1 Hz), 7.71 (d,
H, J = 7.6 Hz), 8.17 (d, 2 H, J = 8.2 Hz) ppm; 1 C NMR (DMSO-d
3
[34] S. Sobhani, E. Safaei, M. Asadi, F. Jalili, J. Organomet. Chem. 693 (2008)
4
6
,
3
313.
[35] M.N. Elinson, A.S. Dorofeev, R.F. Nasybullin, G.I. Nikishin, Synthesis (2008)
933.
TMS): d 12.5, 34.1, 121.5, 124.2, 126.6, 129.5, 129.8, 146.8, 147.2,
1
1
51.2 ppm.
3044 (O–H) cmꢁ1;
m
[36] K. Sujatha, G. Shanthi, N.P. Selvam, S. Manoharan, P.T. Perumal, M. Rajendran,
Bioorg. Med. Chem. Lett., in press, doi:10.1016/j.bmcl.2009.02.113.
[37] R. Naik, P. Joshi, S.P. Kaiwar, R.K. Deshpande, Tetrahedron 59 (2003)
2207.
Compound 10e: mp 230–231 °C; IR (KBr):
1
6
H NMR (DMSO-d , TMS): d 2.32 (s, 6 H), 4.97 (s, 1 H), 7.26 (d, 4
H, J = 8.2 Hz), 7.34 (d, 2 H, J = 8.0 Hz), 7.44 (t, 4 H, J = 7.1 Hz), 7.71
d, 4 H, J = 7.6 Hz) ppm.
[
38] Ch.-H. Lee, J.S. Lindsey, Tetrahedron 50 (1994) 11427.
(