Selective and Efficient Formylation of Indoles (C3) and Pyrroles (C2) Using 2,4,6-Trichloro-1,3,5-Triazine/Dimethylformamide (TCT/DMF) Mixed Reagent

Article abstract of DOI:10.1002/jhet.2652

This study introduces an efficient method for the selective formylation of indoles and pyrroles at the positions of C(3) and C(2), respectively. The mixture of three equivalents of N,N-dimethylformamide and one equivalent of 2,4,6-trichloro-1,3,5-triazine (cyanuric chloride) generates an easy handling formylating agent for the efficient formylation of these classes of compounds to give the corresponding aldehydes under mild reaction conditions. This procedure was highly efficient, and a range of formylated indoles and pyrroles were obtained in good to excellent yields.

Full text of DOI:10.1002/jhet.2652

Month 2016
Selective and Efficient Formylation of Indoles (C3) and Pyrroles (C2)
Using 2,4,6-Trichloro-1,3,5-Triazine/Dimethylformamide (TCT/DMF)
Mixed Reagent
*
Nasser Iranpoor, Farhad Panahi, Soodabeh Erfan, and Fatemeh Roozbin
Department of Chemistry, College of Sciences, Shiraz University, Shiraz 71454, Iran
*
E-mail: iranpoor@susc.ac.ir
Received December 26, 2015
DOI 10.1002/jhet.2652
Published online 00 Month 2016 in Wiley Online Library (wileyonlinelibrary.com).
This study introduces an efficient method for the selective formylation of indoles and pyrroles at the
positions of C(3) and C(2), respectively. The mixture of three equivalents of N,N-dimethylformamide and
one equivalent of 2,4,6-trichloro-1,3,5-triazine (cyanuric chloride) generates an easy handling formylating
agent for the efficient formylation of these classes of compounds to give the corresponding aldehydes under
mild reaction conditions. This procedure was highly efficient, and a range of formylated indoles and pyrroles
were obtained in good to excellent yields.
J. Heterocyclic Chem., 00, 00 (2016).
INTRODUCTION
imidazole/DMF [11], MeOH/Ru [12], CO2/PhMe2SiH [13],
AgOTf/Cl2CHOMe [14], tetramethylethylenediamine/O2/
visible light [15], FeCl3/DMSO [16], CO/acid [17], 2-
benzotriazolyl-1,3-dioxolane [18], N-methyl aniline/Ru [19],
Pd/CO/H2 [20], tert-butyl isocyanide [21], Pd/CH3NO2
[22], etc. In spite of the diversity of formylating agents, there
are serious restrictions for the preparation of some of them,
such as harsh experimental conditions, the use of unusual re-
agents, formation of unwanted or toxic byproducts, use of ex-
pensive procedures for their synthesis, and thermal instability
of the reagents.
2,4,6-Trichloro-1,3,5-triazine (TCT) has been introduced as
an efficient reagent or catalyst in many organic transforma-
tions [23]. This reagent is a stable, nonvolatile, and inexpen-
sive substrate that highlighted it in organic synthesis as an
applicable reagent. Synthesis of benzopyran [24], synthesis
of thiiranes [25], functionalization of glycosides [26], synthe-
sis of 2-substituted benzofurans [27], oxidation of alcohols
Formylation of aromatic compounds for the generation of
aromatic aldehydes is one of the imperative methods in the
synthesis of many materials. Because of the possibility of
transformation of a formyl group to other functionalities, there
is widespread interest in the development of new and efficient
methods for the formylation of aromatic compounds [1].
Moreover, during the multistep synthesis of many natural
products, formylation reaction is often necessary, and the se-
lectivity, simplicity, and efficiency of this step are highly crit-
ical [2]. Some of the widely used formylating agents that have
been reported up to now are POCl3/N,N-dimethylformamide
(DMF) [3], HCO2H/N,N′-Dicyclohexylcarbodiimide (DCC)
[4], 2,2,2-trifluoroethyl formate [5], formic acid/1-Ethyl-3-
(3-dimethylaminopropyl)carbodiimide (EDAC) [6], acetic
formic anhydride [7], formyl-pivaloyl anhydride [8],
cyanomethylformate [9], pentafluorophenyl formate [10],
© 2016 Wiley Periodicals, Inc.

N. Iranpoor, F. Panahi, S. Erfan, and F. Roozbin
Vol 000
[28], synthesis of sulfonamides [29], Beckmann rearrange-
ment [30], synthesis of quinazolinones [31], synthesis of
homoallylic alcohols [32], Friedel–Crafts acylations [33], syn-
thesis of indole derivatives [34], synthesis of α-amino nitriles
[35], and preparation of hydroxamic acids [36] are only part of
the applications of this valuable reagent in organic synthesis.
Combination of TCT and DMF generates an efficient re-
agent that has been used for the formyl protection of pri-
mary hydroxyl groups by Luca et al. for the first time
[37]. This reagent was also used for formylation of enol
ethers [38]. Also, TCT/DMF was used as reagent in the
synthesis of alkyl chlorides and N-alkylphthalimides from
alcohols [39]. The use of this reagent for formylation of
some reactive aromatic compounds has also been reported,
but the generality of the method is limited [40]. In the con-
tinuation of our program on the formylation reactions [41]
and the use of TCT in organic transformations [42], we re-
port herein a novel methodology for the efficient and selec-
tive formylation of indoles and pyrroles under mild
conditions. The method looks efficient for introduction of
the formyl group into such systems and, therefore, can be
of interest for broad circles of synthetic chemists, particu-
larly having in mind the importance of pyrrole/indole
carbaldehydes as building blocks for heterocyclic chemis-
try [43].
functionality tolerance [46]. Also, the C3 formylation of
indoles is an important step in multistep synthesis of many
natural products and biologically active compounds [47].
From this point of view, it seems that the elaboration of
an efficient method that avoids these difficulties is highly
needed. As a result, we set out to optimize the reaction con-
ditions for the formylation of indole as a simple model sub-
strate using TCT/DMF mixed reagent. The results of
optimization study are tabulated in Table 1.
As demonstrated in Table 1, entry 12 shows the most
suitable conditions for the efficient formylation of indole
using TCT/DMF mixed reagent. At ambient temperature,
no product was observed. Also, in the case of using PEG,
THF, acetonitrile, and toluene as solvents, no increase in
the yield was observed. The amount of indole was also
checked, and it was observed that 1Eq of mixed reagent
is enough for formylation of at least 1.2 Eq of indole.
With the optimal conditions in hand, we examined the
scope of the reaction for formylation of different indoles
(Scheme 2).
Indole gave indole-3-carbaldehyde (2a) in 90% isolated
yield. The lower yield obtained for 2-methyl-1H-indole
(2b) may be because of the presence of some steric hin-
drance. 5-Bromo-1H-indole (2c) was less active to some
extent, and only 62% of the product was obtained. 1-
Methyl-1H-indole-3-carbaldehyde (2d) was produced in
74% isolated yield under optimized conditions. Next, few
indole derivatives were synthesized and formylated under
the optimized condition. These results demonstrated that
the TCT/DMF mixed reagent is an efficient, mild, and easy
handling reagent for C3 formylation of indole derivatives
(2e–k). The potential utility of this method in organic syn-
thesis was established in the synthesis of a new cholesterol-
indole derivative (Scheme 3).
As shown in Scheme 3, compound 2l was synthesized
in a three-step process. Compound 1i was synthesized
from indole in a controlled experiment. Addition of cho-
lesterol to 1i resulted in the production of a cholesterol-
indole derivative (1l) [48]. Then, 1l was formylated
using our procedure, and compound 2l was obtained in
68% isolated yield.
RESULTS AND DISCUSSION
The TCT/DMF mixed reagent as formylating reagent is
produced simply using the reaction of TCT and DMF at
room temperature. DMF immediately reacts with TCT
and forms a white solid powder, which is stable under am-
bient conditions. The possible chemical structures of this
salt are shown in Scheme 1.
All of the chemical structures can act as formylating
agent [44]. It should be mentioned that these chemical
structures are proposed for this reagent formed at room
temperature and there are other suggested structures at
higher temperatures [44a,45].
At first, we studied the applicability of using TCT/DMF
mixed reagent for the C(3) formylation of indoles. This re-
action is one of the important methods for direct C(3)
functionalization of indoles; however, the used protocols
suffer from harsh conditions, low selectivity, and lack of
In the synthesis of many biologically active compounds
and natural products containing the pyrrole moiety, C(2)
formylation is significant, and for this reason, the introduc-
tion of efficient methodology for this transformation was
Scheme 1. Four possible forms of DMF/TCT as formylating agent. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]
Journal of Heterocyclic Chemistry
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Formylation of Indoles and Pyrroles
Table 1
molecule could not be formed [50]. Thus, we checked the
activity of some pyrrole derivatives with our method, and
the obtained results are shown in Scheme 4.
Optimization of the reaction conditions.a
As shown in the preceding texts, the TCT/DMF mixed
reagent is efficient for formylation of both indole and
pyrrole derivatives.
In order to show the merit and applicability of our
procedure for formylation of indoles related to other
methods, a comparison with some other reported method-
ologies is presented in Table 2. The results show that our
method is superior to some of the previously reported
conditions in terms of reaction condition, reaction time,
and yield.
In conclusion, we have developed an efficient method
for the C(3) formylation of indole and C(2) formylation
of pyrrole derivatives using TCT/DMF reagent. The syn-
thetic usefulness of this methodology for the synthesis of
aldehydes was demonstrated, and the target products rang-
ing from 2a to 2z were obtained in moderate to good yields
and short reaction times. The method is characterized by its
simplicity, easy handling of the reagents, and the availabil-
ity of the formylating agent employed.
Entry
Solvent
T (°C)
Time (h)
Yield (%)b
1
2
3
4
5
6
7
8
9
None
None
DMF
DMF
DMF
RT
90
90
RT
100
90
Reflux
Reflux
90
90
90
24
2
2
12
2
12
12
12
12
12
5
0
50
90
0
90
0
40
60
0
20
82c
90d
DMF/PEG-600
DMF/THF
DMF/CH3CN
DMF/toluene
DMF/dioxane
DMF
10
11
12
DMF
90
2
aReaction conditions: TCT (1 mmol), DMF (0.5 mL), solvent (1.0 mL),
and indole (1 mmol).
bYield of the isolated product.
c1.5 mmol of indole was used.
d1.2 mmol of indole was used.
EXPERIMENTAL
General experimental details. Chemicals were purchased
considered [49]. Formylation of pyrrole derivatives is
highly sensitive to the conditions used and also the
formylating agent, because under unsuitable conditions,
polymerization and diformylation occur and the target
from Merck and Aldrich chemical companies and used
1
without further purification. H NMR (250MHz) and 13C
NMR (62.9 MHz) spectra were recorded on a Bruker
Scheme 2. Products of C3 formylation of indole derivatives by DMF/TCT reagent. Reaction conditions: TCT (1 mmol), DMF (0.5 mL), solvent (1.0 mL),
and indole (1.2 mmol). All yields are isolated products. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

N. Iranpoor, F. Panahi, S. Erfan, and F. Roozbin
Vol 000
Scheme 3. C3 formylation of a cholesterol-indole derivative using TCT/DMF reagent. [Color figure can be viewed in the online issue, which is available
at wileyonlinelibrary.com.]
Scheme 4. Formylation of some pyrrole derivatives using TCT/DMF reagent. [Color figure can be viewed in the online issue, which is available at
wileyonlinelibrary.com.]
Avance spectrometer in deuterated chloroform (CDCl3)
solution with tetramethylsilane as an internal standard.
Fourier-transform infrared spectroscopy with a Shimadzu
FTIR-8300 spectrophotometer was employed for char-
acterization of products. GC/MS was performed using a
Shimadzu GC MS-QP1000 EX instrument, and results are
given in m/z (rel%). Melting points were determined in open
capillary tubes using a Barnstead electrothermal 9100 BZ
circulating oil melting point apparatus. Reaction monitor-
ing was accomplished with thin-layer chromatography on
silica gel PolyGram SILG/UV254 plates. Column
chromatography was carried out on columns of silica gel
60 (70–230 mesh).
indole substrates (1.2 mmol) and 1mL of DMF as solvent
and stirred for appreciate time specified in Schemes 2–4
at 90°C. When the reaction was completed (monitored by
thin-layer chromatography),
a saturated solution of
Na2CO3 (25 mL) was add to the mixture in order to
hydrolyze the iminium salt for the formation of formyl
group. Then, EtOAc (25 mL) was added to the reaction
mixture. After separation of ethyl acetate layer from H2O,
the aqeous phase was extracted with EtOAc (25 mL)
again. The combined organic layers were then dried
anhydrous Na2SO4, filtered, and concentrated in vacuum
to yield the crude product. The crude product was
purified by column chromatography (n-hexane/EtOAc) to
obtain the desired purity.
General procedure for the formylation of indoles and
pyrroles using TCT/DMF reagent. Into a reaction tube,
TCT [52] (1 mmol, 0.189 g) and DMF (0.5 mL) was
added and permit is to stir for 1 h at room temperature.
Then, the mixture was charged with either pyrrole or
1
Indole-3-carbaldehyde (2a). Yield: 90% (157 mg). H
NMR (250 MHz, CDCl3): δ (ppm) = 7.27–7.33 (m, 3H),
7.84–7.86 (m, 1H), 8.26–8.29 (m, 1H), 10.03 (s, 1H),
11.08 (brs, 1H). 13C NMR (62.5 MHz, acetone-d6): δ
Journal of Heterocyclic Chemistry
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Formylation of Indoles and Pyrroles
Table 2
Comparison of the results of formylation of indole using TCT/DMF reagent and other methods.
Entry
1
Conditions
Yield of product (%)
Ref.
TCT/DMF, 90°C, 2 h
2a: 90
2b: 81
2c: 62
2g: 80
2a: 66
2d: 70
2g: 55
2a: 81
2b: 34
2c:73
This work
2
3
AgOTf, Cl2CHOMe, CH2Cl2, À78 to 0°C, 0.5 h
[14]
[15]
Rose bengal, KI, O2, hv, MeCN/H2O, 60°C, 48 h
4
RuCl3, TBHP, PivOH, N-methyl acetamide, 25°C, 24 h
[19]
5
6
DMSO, H2O, NH4OAc, 150°C, N2, 30 h
TMEDA, O2, CuCl2, DMSO/H2O, 120°C, 4 h
2d: 79
2a: 74
2g: 77
2a: 43
2d: 93
2a: 97
2a: 82
2b: 42
2c: 57
[46h]
[46b]
7
TMEDA, O2, CuCl2, K2CO3, 120°C, 1–3 h
[46c]
8
9
DMF, POCl3, 0°C, NaOH, H2O,
nBu4NI, TBPB, PivOH, DMSO, 80°C, 8 h
[51]
[52]
(ppm) = 111.5, 117.2, 117.3, 126.5, 127.3, 128.8, 142.4,
142.6, 189.8. MS: m/z 145 (41, M+). Anal. Calcd for
C9H7NO (145.16): C, 74.47; H, 4.86; N, 9.65. Found:
C, 74.38; H, 4.75; N, 9.53.
m/z 257 (28, M+). Anal. Calcd for C17H23NO (257.37): C,
79.33; H, 9.01; N, 5.44. Found: C, 79.21; H, 8.92; N, 5.40.
1-(4-Bromobenzyl)indole-3-carbaldehyde (2f). Yield: 88%
1
(331mg). H NMR (250MHz, CDCl3): δ (ppm)=5.10 (s,
2-Methylindole-3 carbaldehyde (2b). Yield: 81% (155mg).
1H NMR (250MHz, CDCl3): δ (ppm)=2.74 (s, 3H), 6.96–
7.26 (m, 3H), 8.21–8.25 (m, 1H), 8.75 (brs, 1H), 10.19 (s,
1H). 13C NMR (62.5MHz, acetone-d6): δ (ppm)=12.0,
112.3, 116.4, 121.6, 123.1, 123.9, 127.8, 136.7, 145.6,
185.1. MS: m/z 159 (36, M+). Anal. Calcd for C10H9NO
(159.18): C, 75.45; H, 5.70; N, 8.80. Found: C, 75.36; H,
5.61; N, 8.73.
5-Bromoindole-3-carbaldehyde (2c). Yield: 62% (167mg).
1H NMR (250MHz, CDCl3): δ (ppm)= 7.17–7.36 (m, 2H),
7.78 (s, 1H), 8.42 (s, 1H), 8.77 (brs, 1H), 9.98 (s, 1H).
MS: m/z 224 (21, M+). Anal. Calcd for C9H6BrNO
(224.05): C, 48.25; H, 2.70; N, 6.25. Found: C, 48.17;
H, 2.61; N, 6.15.
1-Methylindole-3-carbaldehyde (2d). Yield: 74% (141mg).
1H NMR (250MHz, CDCl3): δ (ppm)=3.56 (s, 3H), 7.14–
7.38 (m, 4H), 8.13 (m, 1H), 9.72 (s, 1H). 13C NMR
(62.5 MHz, CDCl3): δ (ppm)= 33.5, 110.0, 117.8, 121.8,
122.8, 123.9, 125.1, 137.9, 139.7, 184.4. Anal. Calcd for
C10H9NO (159.18): C, 75.45; H, 5.70; N, 8.80. Found: C,
75.36; H, 5.63; N, 8.69.
1-Octylindole-3-carbaldehyde (2e). Yield: 90% (277mg).
1H NMR (250MHz, CDCl3): δ (ppm)=0.78–0.79 (m, 3H),
1.17–1.23 (m, 10H), 1.75–1.83 (m, 2H), 4.01–4.07 (t,
J= 7.4 Hz, 2H), 7.20–7.28 (m, 3H), 7.68 (s, 1H), 8.20–8.24
(m, 1H), 9.98 (s, 1H). 13C NMR (62.5MHz, CDCl3): δ
(ppm)= 13.9, 14.1, 22.6, 26.8, 29.1, 29.7, 31.7, 47.3, 110.1,
117.9, 122.1, 122.8, 123.8, 125.4, 137.2, 138.4, 184.5. MS:
2H), 6.84–6.87 (d, J=7.2Hz, 2H), 7.12–7.16 (m, 2H),
7.26–7.30 (m, 5H), 7.52 (s, 1H), 8.17–8.21 (m, 1H), 9.80
(s, 1H). 13C NMR (62.5MHz, CDCl3): δ (ppm)=50.2,
110.4, 118.5, 122.1, 122.3, 123.2, 124.3, 128.8, 132.2,
134.5, 137.2, 138.7, 184.7. MS: m/z 314 (31, M+). Anal.
Calcd for C16HBrNO (314.18): C, 61.17; H, 3.85; N, 4.46.
Found: C, 61.08; H, 3.79; N, 4.40.
1-Allylindole-3-carbaldehyde (2g). Yield: 80% (177mg). 1H
NMR (250MHz, CDCl3): δ (ppm)= 4.56–4.58 (m, 2H), 4.98–
5.17 (m, 2H), 5.78–5.89 (m, 1H), 7.17–7.20 (m, 3H), 7.52 (s,
1H), 8.18–8.20 (m, 1H), 9.82 (s, 1H). 13C NMR (62.5MHz,
CDCl3): δ (ppm)=49.4, 110.4, 118.2, 118.9, 122.0, 123.0,
124.0, 125.3, 131.7, 137.2, 138.7, 184.6. MS: m/z 185 (27,
M+). Anal. Calcd for C12H11NO (185.22): C, 77.81; H, 5.99;
N, 7.56. Found: C, 77.73; H, 5.94; N, 7.51.
1-Decylindole-3-carbaldehyde (2h). Yield: 80% (273mg).
1H NMR (250MHz, CDCl3): δ (ppm)=0.79–0.81 (m, 3H),
1.17–1.23 (m, 14H), 1.79–1.81 (m, 2H), 4.02–4.08 (t,
J=7.5Hz, 2H), 7.20–7.27 (m, 3H), 7.60 (s, 1H), 8.21–8.25
(m, 1H), 9.82 (s, 1H). 13C NMR (62.5MHz, CDCl3): δ
(ppm)=14.1, 22.6, 26.8, 29.1, 29.2, 29.4, 29.5, 29.7, 31.8,
47.3, 110.0, 120.8, 121.9, 122.1, 122.8, 123.9, 135.4,
138.2, 184.5. MS: m/z 285 (30, M+). Anal. Calcd for
C19H27NO (285.42): C, 79.95; H, 9.53; N, 4.91. Found: C,
79.88; H, 9.44; N, 4.82.
1-(5-Bromopentyl)indole-3-carbaldehyde (2i). Yield: 57%
1
(201mg). H NMR (250MHz, CDCl3): δ (ppm)=1.27–
1.39 (m, 2H), 1.58–1.68 (m, 2H), 1.69–1.80 (m, 2H),
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N. Iranpoor, F. Panahi, S. Erfan, and F. Roozbin
Vol 000
3.33–3.37 (t, J=6.2, 2H), 3.97–4.02 (t, J=7.0, 2H), 7.17–
7.22 (m, 3H), 7.54 (s, 1H), 8.18–8.21 (m, 1H), 9.82 (s,
1H). 13C NMR (62.5MHz, CDCl3): δ (ppm)=24.1, 29.0,
32.0, 44.6, 47.0, 110.1, 118.0, 122.1, 122.9, 124.0, 125.4,
137.1, 138.5, 184.5. MS: m/z 294 (21, M+). Anal. Calcd
for C14H16BrNO (294.19): C, 57.16; H, 5.48; N, 4.76.
Found: C, 57.08; H, 5.39; N, 4.71.
199 (32, M+). Anal. Calcd for C13H13NO (199.25): C,
78.36; H, 6.58; N, 7.03. Found: C, 78.27; H, 6.52; N, 6.91.
1-(4-Bromobenzyl)--pyrrole-2-carbaldehyde (2o).
Yield:
86% (272mg). 1H NMR (250MHz, CDCl3): δ (ppm)
= 5.74 (s, 2H), 6.26–6.28 (t, J = 2.5 Hz, 1H), 6.96–67.01
(m, 4H), 7.38–7.41 (d, J = 7.5 Hz, 2H), 9.52 (s, 1H). 13C
NMR (62.5MHz, CDCl3): δ (ppm) =51.38, 110.4, 121.7,
125.1, 129.0, 131.5, 131.8, 136.8, 179.5. MS: m/z 264
(29, M+). Anal. Calcd for C12H10BrNO (264.12): C,
54.57; H, 3.82; N, 5.30. Found: C, 54.49; H, 3.76; N, 5.25.
1-Phenethyl-1H-indole-3-carbaldehyde (2j).
Yield: 86%
1
(256mg). H NMR (250MHz, CDCl3): δ (ppm) = 3.01–
3.07 (t, J=7.4Hz, 2H), 4.26–4.32 (t, J=7.5Hz, 2H), 6.90–
7.29 (m, 9H), 8.21–8.24 (m, 1H), 9.78 (s, 1H). 13C NMR
(62.5MHz, CDCl3): δ (ppm)=36.1, 48.9, 110.0, 117.9,
122.2, 122.9, 124.0, 125.4, 127.1, 128.7, 128.9, 136.6,
137.4, 138.8, 184.5. MS: m/z 249 (44, M+). Anal. Calcd
for C17H15NO (249.31): C, 81.90; H, 6.06; N, 5.62. Found:
C, 81.78; H, 6.00; N, 5.49.
1-Phenyl-H-pyrrole-2-carbaldehyde (2p).
Yield: 81%
1
(166 mg). H NMR (250MHz, CDCl3): δ (ppm) = 6.32–
6.34 (t, J = 2.5, 1H), 6.98–7.39 (m, 7H), 9.59 (s, 1H). 13C
NMR (62.5 MHz, CDCl3):
δ (ppm) = 110.9, 122.0,
126.07, 128.2, 129.10, 131.0, 132.6, 138.75, 179.0. MS:
m/z 171 (28, M+). Anal. Calcd for C11H9NO (171.20): C,
77.17; H, 5.30; N, 8.18. Found: C, 77.10; H, 5.24; N, 8.11.
1-(p-Tolyl)-1H-pyrrole-2-carbaldehyde (2q). Yield: 83%
1-(2-Chloroethyl)-1H-indole-3-carbaldehyde (2k).
Yield:
73% (181 mg). 1H NMR (250 MHz, CDCl3): δ (ppm)
= 3.85–3.90 (t, J = 6.0 Hz, 2H), 4.49–4.54 (t, J= 5.0 Hz,
2H), 7.32–7.36 (m, 3H), 7.79 (s, 1H), 8.32–8.35 (m, 1H),
10.02 (s, 1H). 13C NMR (62.5 MHz, CDCl3): δ (ppm)
= 42.1, 48.7, 109.5, 118.5, 119.4, 122.5, 123.2, 124.3,
136.7, 138.9, 184.7. MS: m/z 207 (25, M+). Anal. Calcd
for C11H10ClNO (207.66): C, 63.63; H, 4.8; N, 6.75.
Found: C, 63.63; H, 4.85; N, 6.75.
1
(184mg). H NMR (250MHz, CDCl3): δ (ppm)=2.35 (s,
3H), 6.32–6.34 (t, J=2.0Hz, 1H), 6.97–7.20 (m, 6H), 9.49
(s, 1H). 13C NMR (62.5MHz, CDCl3): δ (ppm)=21.1,
110.7, 121.6, 125.8, 129.7, 131.0, 132.6, 135.1, 136.7, 179.1.
MS: m/z 185 (19, M+). Anal. Calcd for C12H11NO (185.22):
C, 77.81; H, 5.99; N, 7.56. Found: C, 77.72; H, 5.93; N, 7.50.
1-(4-Bromophenyl)-1H-pyrrole-2-carbaldehyde (2r). Yield:
80% (240mg). 1H NMR (250MHz, CDCl3): δ (ppm)
=6.28–6.30 (t, J=2.2Hz, 1H), 6.97–7.23 (m, 5H), 7.45–
7.50 (m, 1H), 10.01 (s, 1H). 13C NMR (62.5MHz,
CDCl3): δ (ppm)=111.2, 123.7, 129.2, 131.2, 132.3,
134.2, 137.7, 178.8. MS: m/z 250 (24, M+). Anal. Calcd
for C11H8BrNO (250.09): C, 52.83; H, 3.22; N, 5.60.
Found: C, 52.74; H, 3.17; N, 5.52.
1-(4-Chlorophenyl)-1H-pyrrole-2-carbaldehyde (2s). Yield:
85% (209mg). 1H NMR (250MHz, CDCl3): δ (ppm)=6.33–
6.36 (t, J= 3.2 Hz, 1H), 6.96–7.39 (m, 6H), 9.50 (s, 1H). 13C
NMR (62.5 MHz, CDCl3): δ (ppm)=111.1, 123.6, 127.2,
129.2, 131.3, 132.1, 134.1, 137.4, 178.7. MS: m/z 205 (41,
M+). Anal. Calcd for C11H8ClNO (205.64): C, 64.25H,
3.92; N, 6.81. Found: C, 64.17; H, 3.85; N, 6.73.
1-(4-(((3S,8S,9S,10R,13R,14S,17R)-10,13-dimethyl-17-((R)-
6-methylheptan-2-yl)-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetra
decahydro-1H-cyclopenta[a]phenanthren-3-yl)oxy)butyl)-1H-
indole-3-carbaldehyde (2l).
Yield: 68% (478 mg). 1H
NMR (250 MHz, CDCl3): δ (ppm) = 0.78–1.94 (m, 41H),
2.84–2.90 (d, J = 18.0 Hz, 1H), 3.23–3.28 (t, J = 6.5 Hz,
1H), 3.92–4.07 (m, 5H), 6.98–7.57 (m, 5H), 9.54 (s,
1H). 13C NMR (62.5 MHz, CDCl3): δ (ppm) = 19.7,
20.2, 22.6, 23.2, 23.4, 24.4, 26.4, 26.7, 26.8, 28.2, 29.3,
29.8, 30.0, 35.8, 36.2, 37.2, 37.7, 38.8, 39.1, 46.2, 47.7,
56.9, 63.1, 64.1, 71.8, 101.0, 109.3, 119.1, 119.2, 121.0,
121.4, 122.2, 127.7, 134.2, 136.5, 151.9, 183.0. MS:
m/z 585 (39, M+). Anal. Calcd for C40H59NO2 (585.90):
C, 82.00; H, 10.15; N, 2.39. Found: C, 81.91; H, 10.06;
N, 2.32.
1,1′-(1,4-Phenylene)bis(1H-pyrrole-2-carbaldehyde) (2t). Yield:
75% (237mg). 1H NMR (250 MHz, CDCl3): δ (ppm)=6.32–
6.34 (t, J= 2.5Hz, 2H), 6.96–7.16 (m, 6H), 7.48–7.51 (d,
J=7.7 Hz, 2H), 9.48 (s, 2H). 13C NMR (62.5MHz, CDCl3): δ
(ppm) =111.2, 123.7, 127.5, 127.7, 131.3, 132.2, 138.1, 178.7.
MS: m/z 264 (16, M+). Anal. Calcd for C16H12N2O2 (264.28):
C, 72.72; H, 4.58; N, 10.60. Found: C, 72.64; H, 4.51; N, 10.53.
1,1′-(1,3-Phenylenebis(methylene))bis(1H-pyrrole-2-carbaldehyde)
1
Pyrrole-2-carbaldehyde (2m). Yield: 85% (96 mg). H
NMR (250 MHz, CDCl3):
δ (ppm) = 6.34–6.36 (t,
J =2.5 Hz, 1H), 7.01–7.02 (m, 1H), 7.18–7.19 (d,
J =1.0 Hz, 1H), 9.51 (s, 1H), 10.68 (brs, 1H). 13C NMR
(62.5 MHz, CDCl3): δ (ppm) =111.3, 122.1, 127.2, 123.9,
179.6. Anal. Calcd for C5H5NO (95.10): C, 63.15; H,
5.30; N, 14.73. Found: C, 63.07; H, 5.25; N, 14.66.
1-Phenethyl-1H-pyrrole-2-carbaldehyde (2n).
Yield: 89%
(2u).
Yield: 79% (277 mg). 1H NMR (250 MHz,
(212mg). 1H NMR (250MHz, CDCl3): δ (ppm)=2.85–2.91
(t, J=7.6Hz, 2H), 4.32–4.38 (t, J=7.2Hz, 2H), 5.96–5.99
(m, 1H), 6.52 (s, 1H), 6.78–6.79 (m, 1H), 6.95–6.98 (d,
J= 7.5 Hz, 1H), 7.06–7.15 (m, 5H), 9.42 (s, 1H). 13C NMR
(62.5 MHz, CDCl3): δ (ppm)=23.9, 50.8, 109.4, 125.1,
126.6, 128.5, 129.0, 131.1, 131.7, 138.2, 179.2. MS: m/z
CDCl3): δ (ppm) = 5.50 (s, 4H), 6.24–6.26 (t, J = 2.5 Hz,
2H), 6.92–7.25 (m, 8H), 9.52 (s, 2H). 13C NMR
(62.5 MHz, CDCl3): δ (ppm) = 51.7, 110.2, 124.9, 125.9,
126.4, 129.1, 131.5, 138.1, 179.5. MS: m/z 292 (27,
M+). Anal. Calcd for C18H16N2O2 (292.33): C, 73.95;
H, 5.52; N, 9.58. Found: C, 73.86; H, 5.45; N, 9.51.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2016
Formylation of Indoles and Pyrroles
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Journal of Heterocyclic Chemistry
DOI 10.1002/jhet