Direct synthesis of aryl substituted pyrroles from calcium carbide: An underestimated chemical feedstock?

Article abstract of DOI:10.1039/c4gc01615g

In this work, a novel synthetic methodology for the preparation of aryl pyrroles directly from the reaction of calcium carbide with oxime is reported. Various pyrrole derivatives are generated from the corresponding oximes in satisfactory yields (49–88%) under the optimized conditions. The one-pot synthesis of aryl pyrrole from widely available ketone is also successfully developed. A new near-infrared fluorescent BODIPY dye containing a phenyl substitution at the C-3 position is expediently prepared from the aryl pyrrole derived from this methodology. The key benefit of this methodology is the use of an inexpensive and less hazardous primary chemical feedstock, calcium carbide, in a wet solvent without any metal catalysts. This process offers a novel cost-efficient route for the synthesis of functionalized pyrrole.

Full text of DOI:10.1039/c4gc01615g

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Kaewchangwat, R. Sukato, V. Vchirawongkwin, T. Vilaivan, M. Sukwattanasinitt and S. Wacharasindhu,
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Direct synthesis of aryl substituted pyrroles from
Cite this: DOI: 10.1039/x0xx00000x
calcium carbide: an underestimated chemical feedstock
Narongpol Kaewchangwat,a Rangsarit Sukato,a Viwat Vchirawongkwin,b Tirayut
Vilaivan,b Mongkol Sukwattanasinittc and Sumrit Wacharasindhu*c
Received 00th January 2012,
Accepted 00th January 2012
In this work, a novel synthetic methodology for preparation of aryl pyrroles directly from
reactions of calcium carbide with oxime is reported. Various pyrrole derivatives are generated
from the corresponding oximes in satisfactory yields (49ꢀ88%) under the optimized condition.
The oneꢀpot synthesis of aryl pyrrole from wildly available ketone is also successfully
developed. A new near infrared fluorescent BODIPY dye containing phenyl substitution at the
Cꢀ3 position is expediently prepared from the aryl pyrrole derived from this methodology. The
key benefit of this methodology is the use of inexpensive and less hazardous primary chemical
feedstock, calcium carbide, in wet solvent without any metal catalysts. This process offers a
novel cost efficient synthesis of functionalized pyrrole.
DOI: 10.1039/x0xx00000x
www.rsc.org/
Introduction
group and others recently developed methodologies for direct
use of calcium carbide in the synthesis of C
compounds, such as
phenyleneethynylene)s (PPEs),5 polyenynes,6 propagylamine,7
enaminones8 and acetylenic alcohols.9 All reported process
relies on the slow release of calcium carbide into acetylene gas
≡
C containing
poly(pꢀ
diarylethynes,4
One of the key conversion routes along the value added chain
in petrochemical industry is the formation of calcium carbide
from electric arc furnace of coke and lime. The hydrolysis of
calcium carbide gives acetylene gas as one of the major primary
chemical feedstock for a more downstream chemical industry
such as acetic acid, ethanol, aromatics, vinyl acetate, etc
(Scheme 1).1 Although acetylene gas is widely available and
inexpensive, its highly flammable gaseous nature poses serious
disadvantage in extra operation control and cost to prevent
leakage and explosion. In light of industrial safety improvement
without additional cost, a less hazardous and more economical
starting material is highly desirable.2 As a main source of
acetylene gas, solid calcium carbide stands a good chance as a
safer and cheaper alternative to acetylene gas for the production
of acetyleneꢀderived chemicals.
2ꢀ
which then turns into corresponding anion (C2 anion).
Subsequently, the reactive intermediates act as either a coupling
partner for metal catalyzed reaction or a nucleophile for
carbonyl addition.
One of the highest value compounds that can be obtained
from acetylene is 2ꢀaryl pyrrole. It is a basic building block for
pharmaceuticals,10 and fluorescent dyes (BODIPY).11 Current
methods to prepare 2ꢀaryl pyrrole involve either using
unsubstituted pyrrole or ketoxime (Scheme 2). The first method
involves a metal catalysed reaction to introduce the aryl group
to C2ꢀhalogenated pyrroles.12 In addition, direct CꢀH activation
of pyrrole has recently been developed.13 The drawbacks of
these methods are the requirement of precious metal catalyst
and additional protection/deprotection steps in some cases.
Moreover, direct arylation of
Nꢀsubstituted pyrroles with aryl
iodides in the presence of lithium tertꢀbutoxide without the use
of transition metal catalysts has also been reported.14
On the other hand, the readily and inexpensively available
ketoxime can be converted to 2ꢀaryl pyrrole in one step by a
reaction with substituted alkynylcarbonyl compounds or
acetylene gas. The former uses reagent metal catalyst such as
Au and Ni to activate the triple bond.15 The latter (so called
Trofimov reaction) uses acetylene gas, bubbling into the reactor
Scheme 1. Conversion of coal to commodity chemicals
In 2006, Zhang reported the use of calcium carbide as triplet
C–C bond moiety for the synthesis of diarylethynes via
Sonogarshira coupling reaction.3 Following this work, our
This journal is © The Royal Society of Chemistry 2013
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VJieowuArrtnicalelONnlainme e
DOI: 10.1039/C4GC01615G
in the presence of a strong base.16 The Trofimov reaction is a with the over vinylation product 1b in 3 % yield. Switching
preferred method for 2ꢀaryl pyrrole synthesis because metal is from DMSO to DMF result in no reaction (Table 1, entry 2). In
not required in the transformation and the product was directly order to drive the reaction forward the temperature was raised
obtained without additional deprotection step.
from 100 to 120 oC for 24 hour, however, the yield of the
pyrrole 1a decreased along with the increase of the over
vinylation product 1b (Table 1, entry 5). Therefore, controlling
the temperature and the reaction are vital in the reaction
condition (Table 1, entry 5). To increase the base strength, we
therefore added a catalytic amount of 18ꢀcrownꢀ6 as a catalyst
(3% mol) in the reaction mixture. The yield of both pyrroles (1a
and 1b) increased to 65 and 8, respectively (Table 1, entry 6). It
should be noted that under this condition, the crude NMR
indicated that the oxime was completely consumed and no
hydrolysis product (acetophenone) was detected in the reaction
mixture. The slightly low yield of pyrrole 1a is perhaps due to
its air sensitivity and some decomposition may occur during the
chromatographic purification.
Pior art
R
1) Halogenation or NH-protection
Ar
N
N
H
N
R= H,
CO2Me
2) [M] coupling reaction/ Ph-X
H
O
OH
N
/Base
H
H
or
H
CO Me
/ Au(I)
2
Ar
R
Ar
This work
OH
N
CaC2
KOH/ 18-crown-6 (cat)
Ar
N
H
Ar
Table 1. Effect of various parameters on the yield of aryl pyrroles
Scheme 2. Synthetic approach for 2-aryl pyrrole
In this study we proposed a novel process for direct
transformation of calcium carbide into 2ꢀaryl pyrroles (Scheme
2). This is not only an unprecedented application of calcium
carbide as an electrophile precursor in a vinylation reaction to
produce vinylic derivatives but also the first utilization in
heterocycle synthesis. Our methods successfully overcome the
challenge of poor solubility of calcium carbide in organic
solvent and unpolarized nature of acetylenic triple bond to
achieve excellent product yields. The developed method uses
economical starting materials (ketoximes) and avoid handling
of gaseous acetylene. The use of heavy metal is obliterated and
overall process steps are significantly shortened. Therefore it
Entrya
Additive
Base
[equiv.]
Solvent
Yieldb
1a [%]
Yieldb
1b [%]
1
ꢀ
KOH [1.5]
KOH [1.5]
DMSO
DMF
58
0
3
2c
3
ꢀ
0
ꢀ
NaOH [1.5] DMSO
44
48
44
65
32
60
0
4
ꢀ
CsOH [1.5]
KOH [1.5]
KOH [1.5]
KOH [3.0]
KOH [1.5]
DMSO
DMSO
DMSO
DMSO
0
5d
6
ꢀ
8
can be considered as
a convenient, safe, and more
18ꢀcrownꢀ6
18ꢀcrownꢀ6
ꢀ
8
environmental conscious, green and sustainable process.
Moreover, our process can be easily applied in large scale
manufacturing in the chemical industries as well as for routine
laboratory synthesis.
7e
8
12
0
2%H2O:
DMSO
9
ꢀ
KOH [1.5]
KOH [1.5]
10%H2O 32
:DMSO
0
0
Results and Discussion
10
18ꢀcrownꢀ6
2%H2O:
DMSO
73
To design the reaction condition of the calcium carbide we
realized the main problems which are a low solubility of
calcium carbide and a poor electrophilic nature of acetylene gas
which limited its application in organic synthesis. However, a
previous work from Trofimov demonstrated that the use of
aAcetophenone oxime (1 equiv.), CaC2 (6 equiv.), 18ꢀcrownꢀ6 (3
mol%) and solvent (0.074 mM) were heated at 100 oC in a sealed tube
b
for 15 h. Isolated yields after purified by column chromatography on
c
d
neutral alumina. Starting material was recovered in 50% yield. The
reaction was heated to 120oC. Large excess (10 equiv.) of CaC2 was
superbase can promote the
Oꢀalkylation of oximes by acetylene
e
gas.16 Moreover, our work have shown that the use of wet polar
aprotic solvent can slowly hydrolyze the calcium carbide into
acetylene in situ.4 Therefore, we began optimization study by
added.
As mentioned above that all reactions were performed in the
undried solvent. In order to increase the liberation of acetylene,
we added small amount of water in to the reaction (Table 1,
entry 8ꢀ10). The presence of water at 2% w/w with 18ꢀcrownꢀ6
gave the best yield of the product 1a (73%) and has been used
as the optimized condition for further studies. Deliberate
reacting acetophenone oxime (
presence of base to provide the NHꢀ2ꢀaryl pyrrole (1a) along
with ꢀvinyl pyrrole (1b) and the results are depicted in Table
1) with calcium carbide in the
N
1. Among several bases studied including KOH, NaOH and
CsOH (Table 1, entries 1, 3ꢀ4), the best result were obtained
with KOH, providing the desired pyrrole 1a in 58% yield along
2 | J. Name., 2012, 00, 1-3
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addition of water can suppress the formation of vinyl pyrrole
and only trace amount were detected in crude H NMR spectra.
Table 2 Substrate scope of oxime in the reaction with calcium
carbidea
1
In the presence of water, the Nꢀvinylation is sluggish due to the
reduction of basic strength of the KOH in DMSO by the so
called “leveling effect”. However, too much added water (10%)
gave significantly lower yield of 1a perhaps due to the too fast
hydrolysis of calcium carbide making acetylene escape from
the system faster than react with the oxime, and also the
leveling effect that lowering KOH/DMSO basic strength.
Importantly, in comparison with the original Trofimov reaction,
our reaction based on calcium carbide gave a comparable
efficiency, offering an alternative synthesis of 2ꢀaryl pyrroles
that is both convenient and safer to perform. The proposed
mechanism of the reaction between calcium carbide and oxime
are presented in Scheme 3. The added water initially
hydrolyzed calcium carbide to liberate the acetylene gas. The
reaction then proceeded as in standard Trofimov reaction which
involves the addition to acetylene followed by tautomerization
to generate an enamine.1c Next, the enamine underwent a
sigmatropic rearrangement to form an enolꢀimine intermediate.
The desired aryl pyrrole 1a was finally obtained following
tautomerizationꢀadditionꢀdehydration sequence of the enolꢀ
imine intermediate.
1a: 73[79]b/1b: 0[2]b
2a: 52/2b: 0
5a: 49/5b: 0
3a: 51/3b: 0
6a: 50/6b: 0
4a: 51/4b: 5
7a: 88/7b: 0
8a: 59/8b: 2
9a: 38/9b: 0
10a: 57/10b: 2
aOxime (1 equiv), CaC2 (6 equiv), 18ꢀcrownꢀ6 (3mol%) in 2%
water/DMSO (0.074 mM) were heated at 100oC in a sealed tube for 15
h and purified by column chromatography on neutral alumina. bGC
yield from Trofimov reaction16e
Although oxime can be prepared easily, an additional oxime
preparation step is still required. On the other hand, the use of
ketone (the precursor of oxime) as the starting material is
preferred because it allows a convenient oneꢀpot preparation of
2ꢀarylpyrroles. Here, we successfully developed such oneꢀpot
pyrrole synthesis directly from ketone, which combine
combines oxime formation with Trofimov reaction, as shown in
Scheme 5. The ketone 12 was reacted with hydroxylamine
hydrochloride in DMSO at 60 ºC in the presence of a base
(NaHCO3). Addition of calcium carbide and catalytic amounts
of 18ꢀcrownꢀ6 into the reaction mixture led to the formation of
aryl pyrrole (1a) in 56% yield as the sole product. This oneꢀpot
process is comparable to the twoꢀstep transformation in terms
of isolated yield, but is shorter and more convenient to perform.
Scheme 3. Proposed mechanism for the synthesis pyrrole 1a from oxime
1
With the optimized condition in hands, we next expanded the
scope of this reaction by subjecting a variety of oximes ( 11)
into the reaction conditions (table 1). These oxime substrates
were easily prepared from commercially available ketones
using hydroxylamine hydrochloride and purified by
2
ꢀ
recrystallization. A panel of acetophenone oximes (
methyl, chloride, methoxy, butoxyl and dimethyl amine were
successfully transformed into the aryl pyrroles (2a 6a) in
moderate yields along with small amount of over vinylation
products (2b 6b) less than 6% yield. The oxime containing
bicyclic structure such as were also tested on the optimized
condition and generated highly conjugated pyrroles 7a 9a in
2ꢀ6) bearing
ꢀ
ꢀ
7ꢀ9
ꢀ
fair to good yields. The scopes of the reaction also extend to
prepare highly substituted pyrroles. Propiophenone oxime 10
were reacted with calcium carbide under the described
condition to afford the 2,3ꢀdisubstituted pyrrole 10a in 57%
yield along with the corresponding vinylpyrrole 10b in 2%
yield.
Scheme 4. One-pot synthesis of 2-phenyl pyrrole 1a from acetophenone 12
To prove the scope of our methodology, we next
synthesized 3ꢀsubstituted BODIPY (4,4ꢀdifluoroꢀ4ꢀboraꢀ3a,4aꢀ
diazaꢀsꢀindacene) using the aryl pyrrole prepared by our
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methods. Fluorescent BODIPY dyes are widely used as sensors,
optoelectronic material, and imaging applications.11b,17 In recent
years, near infrared (NIR) dyes have attracted much interest for
in vivo imaging applications18 because it allows the bioimaging
with the low interference from the tissue. The high penetration
power and the low energy of the light also caused less cell
damages. To make NIR BODIPY, the post structural
modification of BODIBY scaffold by extension of πꢀ
conjugation such as alkenyl or aryl substitution at the 3ꢀposition
is generally employed.11b The 3ꢀalkenyl substituted BODIPY
are obtained from Knoevenagel reaction of 3ꢀmethyl
BODIPY.11a The preparation of 3ꢀaryl substituted BODIPY
usually involves metalꢀcatalyzed cross coupling reaction of the
haloꢀsubstituted BODIPY, which not only requires additional
step but also causes the partial decomposition of BODIPY
during the coupling reaction.19
Fig. 1 UV-vis absorption and fluorescence emission spectra of BODIPY 14 in THF.
λex = 582 nm
.
Materials and methods
With the readily accessible 2ꢀaryl pyrroles in hands, we
have the opportunity to perform a direct synthesis of BODIPY
fluorophore containing aromatic substitutent at the Cꢀ3
position. Using the standard method,20 the synthesis was
accomplished via a twoꢀstep procedure presented in Scheme 6.
Initially, a condensation of biphenylꢀsubstituted pyrrole 7a with
4ꢀbromobenzaldehyde led to the formation of the dipyrrane 13
in 71% (Scheme 6). The oxidation of 13 using DDQ (2,3ꢀ
All chemicals were obtained from commercial suppliers (Sigma
Aldrich), and were used without further purification. All
solvents were used directly without drying, except for dimethyl
sulfoxide (DMSO), which was dried over 4 Å molecular sieves.
Calcium carbide was ground before use. Analytical thinꢀlayer
chromatography (TLC) was performed on Kieselgel F254 preꢀ
coated plastic TLC plates from EM Science. Visualization was
performed with
a
254 nm ultraviolet lamp. Column
Dichloroꢀ5,6ꢀdicyanoꢀ1,4ꢀbenzoquinone) followed by
a
chromatography was carried out with aluminium oxide (90
active neutral, 70ꢀ230 mesh) from Merck and silica gel (60,
230ꢀ400 mesh) from ICN Silitech. The 1H and 13C NMR
spectra were recorded on a Varian Mercury 400 or Bruker
complexation with BF3·OEt2 gave the desired BODIPY 14 with
the biphenyl substitution at the Cꢀ3 position in 51% yield. The
peripheral bromobenzene moiety at the Cꢀ5 position of 14
provides an opportunity for further probe attachment for
fluorescence sensing applications. The absorption and emission
1
Avance 400 for H (400 MHz) and Bruker Avance 400 for 13C
(100 MHz) in CDCl3 or (CD3)2SO solution. Mass spectra were
performed by Micromass Quattro micro TM API and triple
quadrupole GC/MS from Agilent technologies. The UVꢀvisible
absorption spectra were obtained from Varian Cary 50 UVꢀVis
spectrometer and the fluorescence emission spectra were
recorded on the Varian Cary Eclipse spectrofluorometer.
spectra of the BODIPY 14 are shown in Figure
2. The
maximum absorption and emission wavelengths are at 582 and
623 nm, respectively. It is apparent that the conjugation
extension of the BODIPY scaffold by installation of additional
phenyl groups can shift both absorption and emission maxima
into the far red region.
General procedure for synthesis 2-arylpyrroles
Br
A mixture of calcium carbide (6.0 equiv), ketone oxime (1.0 equiv),
potassium hydroxide (1.5 equiv) and 18ꢀcrownꢀ6 (3.0 mol%) was
suspended in 10 mL of (50:1) DMSO/H2O in a sealed tube. The
reaction mixture was stirred at 100 ºC overnight. The reaction was
cooled to room temperature and diluted by dropwise addition of H2O
(10 mL). The reaction mixture was filtered and extracted solution
into ether (5 × 30 mL). The combined extracts were washed with
brine (2 x 30 mL), dried over MgSO4 and evaporated under reduced
pressure to give the crude product, which was further purified by
column chromatography on alumina (eluted with ethyl acetate /
hexanes = 1: 3) to afford the desired compound.
O
TFA, CH2Cl2
H
+
NH HN
0 oC, 10 min
N
H
Br
71%
Br
7a
13
(i) DDQ, CH2Cl2
rt, 30 min
(ii) DIPEA, BF3-OEt2
0 oC, 30 min
N
F
N
F
B
50% 2 steps
General procedure for one-pot synthesis of 2-phenylpyrrole (1a)
Hydroxylamine hydrochloride (0.83 mmol, 57 mg) was dissolved in
DMSO (10 mL) in a sealed tube with a magnetic stirrer bar, and then
NaHCO3 (0.83 mmol, 93 mg) and acetophenone (0.83 mmol, 100
14
Scheme 5. The synthesis of BODIPY 14 from pyrrole 7a
º
mg) were added. The reaction mixture was stirred at 60 C for 4 h.
After the completion of reaction, calcium carbide (4.98 mmol, 319
mg), potassium hydroxide (1.25 mmol, 70 mg) and 18ꢀcrownꢀ6 were
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º
added and the mixture was heated to 100 C for overnight. The MHz, CDCl3): δ ppm 152.5, 149.2, 147.1, 146.1, 144.7, 133.7,
reaction was cooled to room temperature and diluted by dropwise 133.2, 131.6, 129.4, 128.4, 123.9, 123.4, 120.4, 110.3, 107.4.
1
addition of H2O (10 mL). The reaction mixture was filtered and 2-(Naphthalen-2-yl)pyrrole (9a)12c : H NMR (400 MHz, CDCl3):
extracted solution into ether (5 × 30 mL). The combined extracts δ ppm 8.61 (br, 1H, NH), 7.85 (s, 1H, ArꢀH), 7.84ꢀ7.78 (m, 3H, Arꢀ
were washed with brine (2 x 30 mL), dried over MgSO4 and H), 7.67 (dd, J=8.4,1.6, 2H, ArꢀH), 7.52ꢀ7.36 (m, 2H, ArꢀH), 6.93
evaporated under reduced pressure to give the crude product, which (s, 1H, CH), 6.66 (s, 1H, CH), 6.35 (s, 1H, CH). 13C NMR (100
was further purified by column chromatography on alumina (eluted MHz, CDCl3): δ ppm 133.8, 132.2, 132.1, 130.2, 128.6, 127.8,
with ethyl acetate / hexanes = 1: 3) to afford the corresponding 2ꢀ 127.7, 126.5, 125.4, 123.3, 121.1, 119.2, 110.3, 106.7.; GCꢀMs :
phenylpyrrole as a purple solid (66 mg, 56% yield).
m/z: 193.2
2-Phenylpyrrole (1a)21 : H NMR (400 MHz, CDCl3): δ ppm 8.45 3-Methyl-2-phenylpyrrole (10a)22 : H NMR (400 MHz, CDCl3):
(br, 1H, NH), 7.36 (d, J=8.0 Hz, 2H, ArꢀH), 7.36 (t, J=8.0 Hz, 2H, δ ppm 8.15 (br, 1H, NH), 7.46ꢀ7.32 (m, 5H, ArꢀH), 7.26 (s, 1H, CH),
ArꢀH), 7.11 (1H, d, J=8.0 Hz, ArꢀH), 6.87 (s,1H, CH), 6.53 (s, 1H, 6.78 (s, 1H, CH), 6.16 (s, 1H, CH), 2.29 (s, 3H, CH3).; 13C NMR
CH), 6.31 (s, 1H, CH); 13C NMR (100 MHz, CDCl3): δ ppm 132.8, (100 MHz, CDCl3): δ ppm 133.8, 128.7, 126.4, 126.0, 123.0, 117.3,
132.2, 128.9, 126.2, 123.7, 118.9, 110.1, 106.0. ESIꢀMS calculated 116.2, 112.2, 12.5.; GCꢀMs : m/z: 156.1
1
1
for C10H9N: 143.07, found at 143.01
Synthesis of BODIPY 14
2-p-Tolylpyrrole (2a)12c : 1H NMR (400 MHz, CDCl3): δ ppm 8.41 4ꢀBromobenzaldehyde (0.28 mmol, 52 mg) and 2ꢀ(biphenylꢀ4ꢀ
(br, 1H, NH), 7.37 (d, J=8.0 Hz, 2H, ArꢀH), 7.17 (d, J=8.0 Hz, 2H, yl)pyrrole (7a) (0.558, 122 mg) was dissolved in dichloromethane
ArꢀH), 6.84 (s, 1H, CH), 6.47 (s, 1H, CH), 6.28 (s, 1H, CH), 2.35 (s, (30 mL) in round bottomed flask with a magnetic stirrer bar. The
3H, CH3); 13C NMR (100 MHz, CDCl3): δ ppm 135.9, 132.3, 130.1, reaction mixture was stirred at room temperature for 5 minutes then
129.5, 123.9, 118.4, 110.0, 105.4, 21.1. ; GCꢀMs : m/z: 157.1
a few drops of trifluoroacetic acid was added, and the reaction was
2-(4-Chlorophenyl)pyrrole (3a)12c : H NMR (400 MHz, CDCl3): stirred for another 5 minutes. The reaction was washed with water (3
δ ppm 8.84 (br, 1H, NH), 7.40 (d, J=8.6 Hz, 2H, ArꢀH), 7.33 (d, x 30 mL), dried over MgSO4, and the solvent was removed under
J=8.5 Hz, 2H, ArꢀH), 6.88 (s, 1H, CH), 6.52 (d, J=5.6 Hz, 1H, CH); reduced pressure. Purification by column chromatography on silica
13C NMR (100 MHz, CDCl3): δ ppm 131.8, 131.3, 131.0, 129.0, gel (dichloromethane / hexanes = 1:2) gave compound 13 as a dark
1
125.0, 119.2, 110.4, 106.5.; GCꢀMs : m/z: 177.1
red solid (240 mg, 71% yield). The intermediate 13 (0.196 mmol,
2-(4-Methoxyphenyl)pyrrole (4a)13c 1H NMR (400 MHz, 119 mg) and DDQ (0.196 mmol, 45 mg) was dissolved in
:
CDCl3): δ ppm 8.24 (br, 1H, NH), 7.30 (d, J=8.4 Hz, 2H, ArꢀH), dichloromethane (10 mL) in a round bottomed flask with a magnetic
6.82 (d, J=8.5 Hz, 2H, ArꢀH), 6.72 (s, 1H, CH), 6.32 (s, 1H, CH), stirrer bar under nitrogen atmosphere. The reaction mixture was
6.19 (s, 1H, CH), 3.73 (s, 3H, OCH3); 13C NMR (100 MHz, CDCl3): stirred at room temperature for 30 minutes. Then N,Nꢀ
δ ppm 158.3, 132.2, 126.0, 125.3, 118.2, 114.4, 109.9, 104.9, 55.35.; diisopropylethylamine (1.97 mmol, 0.34 mL) and boron trifluoride
GCꢀMs : m/z: 173.1
diethyl etherate (2.36 mmol, 0.30 mL) were added at 0 ºC and the
1
2-(4-Butoxyphenyl)pyrrole (5a) : H NMR (400 MHz, CDCl3): δ mixture was stirred for 30 minutes. The reaction was washed with
ppm 8.33 (br, 1H, NH), 7.39 (d, J=8.6 Hz, 2H, ArꢀH), 6.90 (d, J=8.3 saturated NaHCO3 (3 x 30 mL), brine (3 x 30 mL), dried over
Hz, 2H, ArꢀH), 6.83 (s, 1H, CH), 6.40 (s, 1H, CH), 6.27 (s, 1H, CH), MgSO4 and the solvent was removed under reduced pressure. The
3.97 (t, J=6.5 Hz, 2H, OCH2), 1.82ꢀ1.73 (m, 2H, CH2), 1.50 (q, residue was purified by column chromatography on silica gel
J=8.0 Hz, 2H, CH2), 0.98 (t, J=7.2 Hz, 3H, CH3); 13C NMR (100 (dichloromethane / hexanes = 1:2) to give the product as a red solid
1
MHz, CDCl3): δ ppm 157.9, 132.3, 130.6, 125.8, 125.3, 118.1, (129 mg, 50% yield. H NMR (400 MHz, CDCl3): δ ppm 8.00 (d,
115.0, 109.9, 104.8, 67.8, 31.4, 19.3, 13.3.; GCꢀMs : m/z: 215.2
J=8.4 Hz, 4H, ArꢀH), 7.73ꢀ7.61 (m, 10H, ArꢀH), 7.52ꢀ7.42 (m, 6H,
N,N-Dimethyl-4-(pyrrol-2-yl)aniline (6a)12d : 1H NMR (400 MHz, ArꢀH), 7.37 (d, J=7.4 Hz, 2H, ArꢀH), 6.89 (d, J=4.4 Hz, 2H, CH),
CDCl3): δ ppm 8.31 (br, 1H, NH), 7.37 (d, J=8.7 Hz, 2H, ArꢀH), 6.72 (d, J=4.2 Hz, 2H, CH).; 13C NMR (100 MHz, CDCl3): δ ppm
6.80 (s, 1H, CH). 6.77 (d, J=8.5 Hz, 2H, ArꢀH), 6.36 (s, 1H, CH), 142.4, 140.5, 136.4, 133.3, 132.0, 131.7, 131.4, 130.5, 130.0, 130.0,
6.28 (s, 1H, CH), 2.97 (s, 6H, NꢀCH3); 13C NMR (100 MHz, 129.9, 128.8, 127.6, 127.2, 127.0, 124.7, 121.2. HRMS (ESI)
CDCl3): δ ppm 149.3, 132.9, 125.1, 125.1, 122.0, 117.5, 113.0, calculated for [M+Na]+: 673.1238, found at 673.1232.
109.7, 103.9, 40.6.; GCꢀMs: m/z: 186.2
1
2-(Biphenyl-4-yl)pyrrole (7a)12c : H NMR (400 MHz, CDCl3): δ
Conclusions
ppm 8.48 (br, 1H, NH), 7.62 (d, J=8.3 Hz, 4H, ArꢀH), 7.55 (d, J=8.4
In summary, a practical synthesis of 2ꢀarylpyrroles from
Hz, 2H, ArꢀH), 7.45 (t, J=7.6 Hz, 2H, ArꢀH), 7.34 (t, J=7.4 Hz, 1H,
calcium carbide and oximes was successfully developed. The
ArꢀH), 6.90 (s, 1H, CH), 6.58 (s, 1H, CH), 6.32 (s, 1H, CH); 13C
reaction was carried out in wet solvent without the use of toxic
NMR (100 MHz, CDCl3): δ ppm 140.7, 138.9, 131.8, 128.8, 127.5,
metal. Moreover, the process was extended to prepare 2ꢀ
127.2, 126.8, 124.2, 118.9, 110.3, 106.2.; GCꢀMs : m/z: 219.1
arylpyrroles in oneꢀpot manner starting from acetophenone and
hydroxylamine. The resulting aryl pyrroles prove to be an
excellent building block for NIRꢀBODIPY fluorophores. These
novel synthetic methods provide an opportunity to position calcium
carbide as a sustainable and cost efficient carbon source in modern
chemical industries.
3-(4-(Pyrrol-2-yl)phenyl)pyridine (8a) : 1H NMR (400 MHz,
CDCl3): δ ppm 9.40 (br, 1H, NH), 8.94 (s, 1H, ), 8.85 (1H, d, J=5.2
Hz), 8.58 (1H, s), 8.41 (1H, d, J=4.6 Hz) 7.96 (1H, d, J=8.0 Hz),
7.81 (1H, d, J=9.2 Hz), 7.30 (2H, d, J=4.0 Hz), 6.93 (1H, d, J=1.9
Hz), 6.59 (1H, d, J=1.1 Hz), 6.31 (1H, d, J=2.4 Hz).; 13C NMR (100
This journal is © The Royal Society of Chemistry 2012
J. Name., 2012, 00, 1-3 | 5

Page 7 of 8
ARTICLE
Green Chemistry
VJieowuArrtnicalelONnlainme e
DOI: 10.1039/C4GC01615G
11 (a) Y. Ni, L. Zeng, N. Y. Kang, K. W. Huang, L. Wang, Z. Zeng, Y.
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Fund (TRFꢀRSA5780055) and Nanotechnology Center
(NANOTEC), NSTDA, Ministry of Science and Technology,
Thailand, through its program of Center of Excellence
Network. This work is part of the Project for Establishment of
Comprehensive Center for Innovative Food, Health Products
and Agriculture supported by the Thai Government Stimulus
Package 2 (TKK2555, SP2), the Higher Education Research
Promotion and National Research University Project of
Thailand, Office of the Higher Education Commission
(AM1006Aꢀ56) and the Ratchadaphiseksomphot Endowment
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