Phosphoric acid-promoted synthesis of 4-acylpyrrole-2-carboxylic esters and dipyrryl ketones from mixed anhydrides

Article abstract of DOI:10.1021/jo051906w

An efficient synthesis of 4-acylpyrrole-2-carboxylic esters utilizing a phosphoric acid-catalyzed mixed anhydride system is described. The new route also enables the preparation of dipyrryl ketones and N-confused dipyrryl ketones.

Full text of DOI:10.1021/jo051906w

Phosphoric Acid-Promoted Synthesis of
4
-Acylpyrrole-2-carboxylic Esters and
Dipyrryl Ketones from Mixed Anhydrides
FIGURE 1. Knight’s acylation methodology.5
Cory S. Beshara and Alison Thompson*
SCHEME 1. Trifluoroacetylation of 1
Department of Chemistry, Dalhousie University,
Halifax, Nova Scotia, Canada B3H 4J3
alison.thompson@dal.ca
Received September 11, 2005
TABLE 1. Attempted Syntheses of
4-Acylpyrrole-2-carboxylic Esters with RCO2H and TFAA
a
entry
acid
temp (°C) product yield (%)
1
2
3
4
5
6
4-nitrocinnamic
3,5-dimethoxybenzoic
benzoic
4-ethoxybenzoic
palmitic
propanoic
20
20
20
20
20
20
4a
4b
4c
4d
4e
4f
NR
NR
NR
60
An efficient synthesis of 4-acylpyrrole-2-carboxylic esters
utilizing a phosphoric acid-catalyzed mixed anhydride sys-
tem is described. The new route also enables the preparation
of dipyrryl ketones and N-confused dipyrryl ketones.
60
b
96
a
NR: no reaction. b Carboxylic acid used in 5-fold excess.
9
1
1), resulted in a disappointing product yield of 51%.
Treating 1 with trifluoroacetic acid (TFA) in the presence
of TFAA (method B, Scheme 1), according to Knight’s
4
-Acylpyrrole-2-carboxylic esters are useful intermedi-
ates for the synthesis of a wide range of pyrrolic com-
pounds. The acylation of pyrrole-2-carboxylic esters is
most easily achieved by using acid chlorides, catalyzed
5
procedure, gave the pyrrole 2 in excellent yield. Encour-
2
aged by this success we attempted to apply Knight’s
methodology to the preparation of other 4-acylpyrrole-
2-carboxylic esters. Thus, several attempts with pyrrole
4
by Lewis acids such as SnCl . The use of trifluoroacetic
anhydride (TFAA) to produce mixed anhydrides for use
3
in acylation chemistry is well-known and the use of
1
, using a carboxylic acid in place of TFA, were made
and the results are presented in Table 1.
phosphoric acid as a catalyst in TFAA/mixed anhydride
4
chemistry was first described by Galli. Knight and co-
5
workers have recently described a method for the
Analysis of Table 1 reveals that electron-poor aryl acids
(entries 1 and 2), or even benzoic acid itself (entry 3),
did not result in acylated pyrrole. Aliphatic and electron-
rich aryl carboxylic acids gave good yields (entries 4-6).
Given the lack of reactivity of electron-poor carboxylic
acids under these conditions, it became clear that Knight’s
method was not general for the acylation of pyrrole-2-
carboxylic esters unsubstituted in the 4-position.
2
-acylation of N-substituted pyrroles involving carboxylic
acids and TFAA (Figure 1). The reaction proceeds via the
formation of the mixed anhydride that results from the
reaction of TFAA with a carboxylic acid. Knight’s method
is similar to those reported by Galli (thiophene) and
Kakushima (pyrrole) and produces good yields of 2-acy-
6
7
lated pyrroles.
As part of our research into the synthesis of homochiral
bis(dipyrromethene)s, we needed a route by which to
prepare 4-trifluoroacetylpyrrole-2-carboxylic esters. Our
first attempt to synthesize 2, by the trifluoroacetylation
of 1 using TFAA and DMAP in DCM (method A, Scheme
The use of acyl trifluoroacetates (ATFA) as mixed
anhydrides for the acylation of aromatic heterocyles and
activated benzene rings has been previously reported.
Indeed, ATFA has been used as a successful acylating
8
agent for thiophene, anisole, and furan but is less
successful for the acylation of pyrrole.1
,10,11
Clementi’s
(
1) Jones, A. R.; Bean, G. P., Eds. The Chemistry of Pyrroles;
work in this area indicates that the trifluoroacetylation
of pyrrole becomes competitive with acylation upon a
decrease in temperature, solvent polarity, and reactant
concentration.12
Academic Press: London,UK, 1977.
(
2) Wijesekera, T. P.; Paine, J. B., III; Dolphin, D. J. Org. Chem.
1
988, 53, 1345-1352.
(
(
(
3) Tedder, J. M. Chem. Rev. 1955, 787, 7-827.
4) Galli, C. Synthesis 1979, 303-304.
5) Song, C.; Knight, D. W.; Whatton, M. A. Tetrahedron Lett. 2004,
4
5, 9573-9576.
(9) Burns, D. H.; Li, Y. H.; Shi, D. C.; Caldwell, T. M. J. Org. Chem.
2002, 67, 4536-4546.
(10) Clementi, S.; Genel, F.; Marino, G. Ric. Sci. 1967, 37, 418-
423.
(
6) Galli, C.; Illuminati, G.; Mandolini, L. J. Org. Chem. 1980, 45,
-315.
7) Kakushima, M.; Hamel, P.; Frenette, R.; Rokach, J. J. Org.
1
(
Chem. 1983, 48, 3214-3219.
8) Wood, T. E.; Dalgleish, N. D.; Power, E. D.; Thompson, A.; Chen,
X.; Okamoto, Y. J. Am. Chem. Soc. 2005, 127, 5740-5741.
(11) Thompson, A.; Gao, S.; Modzelewska, G.; Hughes, D. S.; Patrick,
B.; Dolphin, D. Org. Lett. 2000, 2, 3587-3590.
(12) Clementi, S.; Marino, M. Gazzetta 1970, 100, 556-565.
(
1
0.1021/jo051906w CCC: $30.25 © 2005 American Chemical Society
Published on Web 11/10/2005
J. Org. Chem. 2005, 70, 10607-10610
10607

SCHEME 2. Phosphoric Acid-Promoted Synthesis
of 4-Acylpyrrole-2-carboxylic Esters
TABLE 2. Synthesis of 4-Acylpyrrole-2-carboxylic
Esters with Phosphoric Acid-Derived Mixed Anhydrides
a
entry
acid
temp (°C) product yield (%)
1
2
3
4
5
6
7
8
9
palmitic
20
20
20
20
20
20
20
40
20
4e
4f
4g
4h
4i
4c
4b
4b
4a
77
90
83
86
66
81
81
62
NR
propanoic
acetic
pivalic
iso-valeric
benzoic
b
3,5-dimethoxybenzoic
3,5-dimethoxybenzoic
4-nitrocinnamic
a
NR: no reaction. b No solvent; heated to form B.
roles18,19 but with lower yields. The order of addition and,
presumably, successful formation of the phosphoryl
mixed anhydride C, prior to the addition of the pyrrole,
is key to the higher yields obtained in our reactions. Thus
in one flask we mixed phosphoric acid with 2 equiv of
1
9
TFAA to generate A, for which Smyth has reported
F
and 31P NMR spectroscopic evidence. In another flask,
equiv of TFAA were added to a solution (or suspension)
of the carboxylic acid in CH CN to generate B. The TFAA/
PO mixture (A) was then added to the solution
15
2
3
H
3
4
containing B, presumably then generating the required
phosphoryl mixed anhydride C. Pyrrole 3 was then added
within 2 min and the reaction mixture was stirred for 5
min. Routine workup and purification gave the expected
4-acylpyrrole-2-carboxylic esters (Table 2).
Smyth and co-workers have proposed that Friedel-
Crafts acylations of substituted benzenes with TFAA and
phosphoric acid are a clean alternative to conventional
methods utilizing Lewis acid catalysts.1
3-15
Recyclability
of TFAA after the reaction through treatment of the
resultant TFA with a dehydrating agent (e.g., P
The reaction was very rapid after the addition of
pyrrole and usually complete (or close to completion)
within 5 min. The use of aliphatic acids (entries 1-5)
gave the corresponding 4-acylpyrrole-2-carboxylic esters
in very good yield. Benzoic acid, previously unreactive
(Table 1, entry 3), gave the required acylated pyrrole in
81% yield (Table 2, entry 6). In the case of 3,5-
dimethoxybenzoic acid it was found that the yield could
be significantly improved by conducting the reaction in
the absence of solvent (entry 7), and ensuring the efficient
formation of B by heating to reflux. Unfortunately,
similar attempts with p-nitrocinnamic acid proved fruit-
2 5
O )
contributes to the efficiency of the process. The degree
of activation is significant as the activated phosphoryl
mixed anhydrides react rapidly and so Lewis acid co-
catalysis is unnecessary, in contrast to when using acyl
1
5
chlorides.
Considering the success of utilizing both phosphoric
acid to promote acylations and the beneficial effects of
1
2
polar solvents to enhance the acylation of thiophene,
we decided to merge these two approaches for the
4
-acylation of pyrrole-2-carboxylic esters. In our modified
1
7
procedure, pyrrole 3 was added as a solid to a solution
containing, presumably, a pre-formed phosphoryl mixed
anhydride C, synthesized stepwise in a manner similar
to that of Smyth (Scheme 2).16 The reaction, not rigor-
ously protected from oxygen, was followed by monitoring
the disappearance of 3 by TLC. Analysis of Table 2
reveals that, under these conditions, excellent yields of
-acylpyrrole-2-carboxylic esters were obtained with car-
boxylic acids that were previously unsuccessful or low
yielding.
less (entry 9), akin to similar reports involving indoles.
Many of the reactions could also be conducted in the
absence of CH CN, with similar yields obtained. How-
3
ever, on occasion we observed that the carboxylic acid
was not miscible with TFAA and this lack of miscibility
was usually indicative that no 4-acylpyrrole-2-carboxylic
ester would be produced (if the reaction was carried out
as usual). However, if acetonitrile was added to the
formation of B, and the acylation only carried out upon
the disappearance of the suspended carboxylic acid, the
required 4-acylpyrrole-2-carboxylic ester was isolated in
good yield. It is thus evident that the formation of the
initial mixed anhydride B between the carboxylic acid
and TFAA must occur first, before the addition of A and
the pyrrole, if good product yields are to be obtained. As
4
Murakami and co-workers have reported similar phos-
17
phoric acid-promoted acylations of indole and pyr-
(
13) Gray, A. D.; Smyth, T. P. J. Org. Chem. 2001, 66, 7113-7117.
14) Smyth, T. P.; Corby, B. W. Org. Proc. Res. Dev. 1997, 1, 264-
(
2
67.
3
such, our preferred procedure was to routinely use CH -
CN in the preparation of B.
Having established that our new procedure could be
used for the efficient formation of 4-acylpyrrole-2-car-
(
(
15) Smyth, T. P.; Corby, B. W. J. Org. Chem. 1998, 63, 8946-8951.
16) Smyth et al. (ref 14) mixed TFAA (4 equiv) with the carboxylic
acid (1 equiv) followed, upon cooling to below 10 °C, by 85% phosphoric
acid (1 equiv). After complete dissolution of the phosphoric acid the
substrate was added. In our work, phosophoric acid (1 equiv) was added
to TFAA (2 equiv) at 0 °C and the carboxylic acid (1 equiv) was stirred
separately with TFAA (2 equiv) in acetonitrile at room temperature.
Upon solvation of the phosphoric acid solution, the two components
were mixed and then the substrate was added as a solid within 2 min.
(18) Tani, M.; Ariyasu, T.; Nishiyama, C.; Hagiwara, H.; Watanabe,
T.; Yokoyama, Y.; Murakami, Y. Chem. Pharm. Bull. 1996, 44, 48-
54.
(19) Tani, M.; Ariyasu, T.; Ohtsuka, M.; Koga, T.; Ogawa, Y.;
Yokoyama, Y.; Murakami, Y. Chem. Pharm. Bull. 1996, 44, 55-61.
(
17) Murakami, Y.; Tani, M.; Suzuki, M.; Sudoh, K.; Uesato, M.;
Tanaka, K.; Yokoyama, Y. Chem. Pharm. Bull. 1985, 33, 7-4716.
10608 J. Org. Chem., Vol. 70, No. 25, 2005

SCHEME 3. Synthesis of Dipyrryl Ketones
Experimental Section
General Procedure for the Synthesis of Ketones. For-
mation of A: H PO (85%, 0.041 mL, 0.59 mmol) was added
3 4
jet-wise to TFAA (0.166 mL, 1.2 mmol) that was being stirred
at 0 °C. The solution was allowed to stir at this temperature
until homogeneous (the reaction mixture goes through a white
precipitous stage prior to the achievement of complete homoge-
neity). Concurrent with the formation of A, B was prepared.
Formation of B: TFAA (0.166 mL, 1.2 mmol) was added to a
solution/suspension of carboxylic acid (0.59 mmol) and CH
3
CN
(
1 mL). The reaction mixture was stirred for 10 min (or until
the disappearance of insoluble suspended carboxylic acids).
Mixture A was then added to the solution of B in one portion.
This mixture was allowed to stir briefly (30 s to 2 min) and
pyrrole 3 (0.100 g, 0.59 mmol) was then added as a solid. The
reaction was then allowed to stir until the disappearance of 3
was confirmed by TLC analysis (5 min; 3:7 ethyl acetate:
hexanes, R
f
0.69). Upon completion, the reaction was quenched
CO (added dropwise slowly) until the
with 10% aqueous Na
2
3
cessation of effervescence, followed by an additional 20 mL.
Note: Some ketones precipitated at this point and were filtered,
while others were extracted with CH
Cl
2 2
(3 × 10 mL). Purifica-
tion with flash chromatography on silica gel and a gradient
elution (19:1 hexanes:ethyl acetate-4:1 hexanes:ethyl acetate)
gave the required compound.
4
-Benzoyl-3,5-dimethyl-1H-pyrrole-2-carboxylic Acid Eth-
yl Ester (4c). Light yellow solid (0.132 g, 81%). Mp 111-112
C. NMR (CDCl ) δ
°
3
H
1.37 (3H, t, J ) 7 Hz), 2.24 (3H, s), 2.25
(
3H, s), 4.34 (2H, q, J ) 7 Hz), 7.43 (2H, t, J ) 1.5 Hz), 7.54
boxylic esters, we turned our attention to the synthesis
of dipyrryl ketones. Dipyrryl ketones have been used as
synthetic intermediates in the synthesis of oxophlorins/
oxyporphyrins, which are themselves intermediates for
biologically important protoporphyrins.20,21 Symmetric
(
1H, t, J ) 1.5 Hz), 7.73 (2H, d, J ) 1.5 Hz), 9.56 (1H, br s);
NMR (CDCl
3
) δ
C
12.6, 13.9, 14.9, 60.7, 118.8, 123.5, 128.6, 129.5,
1
29.6, 132.5, 137.3, 140.7, 162.3, 194.3. m/z 564.9 (dimer as Na
adduct). R
f
0.39.
4-(3,5-Dimethoxybenzoyl)-3,5-dimethyl-1H-pyrrole-2-car-
boxylic Acid Ethyl Ester (4b). White solid (0.121 g, 81%).
Starting material (0.025 g) was recovered under solvent-free
2
,2′-dipyrryl ketones have previously been constructed
22
through the use of phosgene, or thiophosgene followed
by reaction with basic hydrogen peroxide.23 Other known
synthetic routes of dipyrryl ketones include the oxidation
3 H
conditions. Mp 183-185 °C. NMR (CDCl ) δ 1.38 (3H, t, J ) 7
Hz), 2.28 (6H, s), 3.83 (6H, s), 4.34 (2H, q, J ) 7 Hz), 6.64 (1H,
t, J ) 2.5 Hz), 6.90 (2H, d, J ) 2.5 Hz), 9.05 (1H, br s); NMR
(CDCl ) δ 12.2, 13.6, 14.5, 55.6, 60.4, 104.6, 106.5, 118.5, 123.2,
12
of dipyrromethanes with lead tetraacetate/lead oxide,
3
C
sulfuryl chloride,12 and ceric ammonium nitrate.24
129.3, 136.6, 142.3, 160.8, 161.6, 193.4. m/z 684.8 (dimer as Na
adduct). R 0.26.
-Hexadecanoyl-3,5-dimethyl-1H-pyrrole-2-carboxylic
Acid Ethyl Ester (4e). White solid (0.185 g, 77%). Mp 93-94
C. NMR (CDCl ) δ 0.88 (3H, t, J ) 7 Hz), 1.25 (24H, m), 1.35
3H, t, J ) 7 Hz), 1.68 (2H, p, J ) 7 Hz), 2.51 (3H, s), 2.59 (3H,
s), 2.72 (2H, t, J ) 7 Hz), 4.33 (2H, q, J ) 7 Hz), 9.06 (1H, br s);
NMR (CDCl ) δ 13.05, 14.6, 14.8, 15.5, 23.0, 24.6, 29.7, 29.8,
9.9, 29.9, 30.0, 32.3, 43.3, 60.7, 118.2, 124.0, 129.3, 138.0, 162.0,
98.9. m/z 833.1 (dimer as Na adduct). R 0.60.
,5-Dimethyl-4-propionyl-1H-pyrrole-2-carboxylic Acid
Ethyl Ester (4f). White solid (0.120 g, 90%). Mp 143-144 °C.
NMR (CDCl ) δ : 1.17 (3H, t, J ) 7.5), 1.38 (3H, t, J ) 7 Hz),
.53 (3H, s), 2.60 (3H, s), 2.76 (2H, q, J ) 7.5 Hz), 4.34 (2H, q,
J ) 7 Hz), 9.27 (1H, br s); NMR (CDCl ) δ 8.5, 13.1, 14.8, 15.5,
36.3, 60.7, 118.2, 123.7, 129.4, 138.2, 162.1, 199.0. m/z 468.9
dimer as sodium adduct). R 0.39.
-Acetyl-3,5-dimethyl-1H-pyrrole-2-carboxylic Acid Eth-
f
To investigate the scope of the phosphoric acid-
promoted mixed anhydride reaction for the synthesis of
dipyrryl ketones, we reacted pyrrolyl carboxylic acids
with 3. Thus, two pyrrolyl carboxylic acids, 5 and 6, were
used in conjunction with 3 to produce N-confused dipyrryl
ketones, 7 and 8, potential precursors to N-confused and/
or N-fused porphyrins. The same methodology was used
for the construction of 2,2′-dipyrryl ketone 9 (Scheme 3).
Compounds analogous to 9 have been used to construct
oxophlorins (oxoporphyrins).25 These results demonstrate
that it is possible to prepare dipyrryl ketones with a
variety of architectures simply by using different pyrrolyl
carboxylic acids and R/â-free pyrrole nucleophiles.
In conclusion our new procedure for the synthesis of
4
°
(
3
H
3
C
2
1
f
3
3
H
2
3
C
(
f
4
4
-acylpyrrole-2-carboxylic esters gives improved yields
yl Ester (4g). White solid (0.104 g, 83%). Mp 143-145 °C. NMR
over existing methods and enables a new route to dipyrryl
ketones, both N-confused and 2,2′-dipyrryl ketones. The
procedure is facile to follow and the acylation proceeds
rapidly.
(
CDCl
3
) δ
H
1.38 (3H, t, J ) 7 Hz), 2.45 (3H, s), 2.53 (3H, s), 2.59
) δ
(
3H, s), 4.34 (2H, q, J ) 7 Hz), 9.14 (1H, br s); NMR (CDCl
3
C
13.0, 14.8, 15.5, 31.6, 60.7, 118.3, 123.9, 129.6, 138.5, 162.0,
195.8. m/z 440.9 (dimer as Na adduct). R 0.26.
-(2,2-Dimethylpropionyl)-3,5-dimethyl-1H-pyrrole-2-
carboxylic Acid Ethyl Ester (4h). White solid (0.129 g, 86%).
Mp 144-146 °C. NMR (CDCl ) δ 1.24 (9H, s), 1.39 (3H, t, J )
7 Hz), 2.24 (3H, s), 2.27 (3H, s), 4.34 (2H, q, J ) 7 Hz), 9.12
(1H, br s); NMR (CDCl ) δ 12.7, 13.4, 14.8, 27.3, 45.8, 60.4,
18.2, 125.8, 126.1, 129.5, 162.0, 213.0. m/z 524.9 (dimer as Na
adduct). R 0.49.
,5-Dimethyl-4-(3-methylbutyryl)-1H-pyrrole-2-carboxy-
lic Acid Ethyl Ester (4i). White solid (0.099 g, 66%). Mp 97-
99 °C. NMR (CDCl ) δ 0.97 (6H, d, J ) 7 Hz), 1.37 (3H, t, J )
f
4
(
(
20) Clezy, P. S.; Liepa, A. J. Aust. J. Chem. 1970, 23, 2443-2459.
21) Chen, Q.; Huggins, M. T.; Lightner, D. A.; Norona, W.; McDon-
3
H
agh, A. F. J. Am. Chem. Soc. 1999, 121, 9253-9264.
(
(
22) Fischer, H.; Orth, H. Liebigs Ann. Chem. 1931, 62-86.
3
C
23) de Groot, J. A.; Koek, K. H.; Lugtenbeurg, J. Recl. Trav. Chim.
1
Pays-Bas 1981, 100, 405-408.
f
(
24) Paine, J. B., III; Dolphin, D. Can. J. Chem. 1976, 54, 411-
14.
25) Paine, J. B., III In The Porphyrins; Dolphin, D., Ed.; Academic
Press: New York, 1978; Vol. I, Chapter 4.
3
4
(
3
H
J. Org. Chem, Vol. 70, No. 25, 2005 10609

2
6
7
(
(
1
0
Hz), 2.24 (1H, n, J ) 7 Hz), 2.51 (3H, s), 2.57 (3H, s), 2.61
2H, d, J ) 7 Hz), 4.34 (2H, q, J ) 7 Hz), 9.27 (1H, br s); NMR
CDCl ) δ 12.7, 14.8, 15.0, 22.8, 25.0, 51.9, 60.4, 117.9, 124.0,
28.9, 137.6, 161.8, 198.4. m/z 524.9 (dimer as Na adduct). R
.49.
-(3,5-Dimethyl-1H-pyrrole-2-carbonyl-4-carboxylic acid
solid (0.88 g, 37%). Fischer reported colorless needles. Mp 226-
2
6
227 °C (lit. mp 221 °C). NMR (DMSO-d
6
) δ
H
1.28 (3H, t, J ) 7
3
C
Hz), 2.21 (3H, s), 2.44 (3H, s), 4.19 (2H, q, J ) 7 Hz), 11.74 (1H,
f
br s); NMR (DMSO-d ) δ 12.5, 14.0, 14.8, 59.3, 112.7, 128.0,
6 C
128.4, 139.9, 165.2, 179.7. m/z 742.8 (dimer as Na adduct). R
f
4
0.16.
ethyl ester)-3,5-dimethyl-1H-pyrrole-2-carboxylic Acid Eth-
yl Ester (7). Off-white solid (0.155 g, 72%). Mp 213-214 °C. NMR
Acknowledgment. This research was supported by
the Natural Sciences and Engineering Research Council
of Canada and Dalhousie University. We are grateful
to the Canada Foundation for Innovation and the Nova
Scotia Research Innovation Trust for research infra-
structure. C.S.B. thanks the Sumner Foundation for
scholarship awards.
(
CDCl
3H, s), 2.30 (3H, s), 2.31 (3H, s), 2.60 (3H, s), 4.28 (2H, q, J )
Hz), 4.35 (2H, q, J ) 7 Hz), 9.52 (1H, br s), 10.06 (1H, br s);
NMR (CDCl ) δ 11.6, 12.3, 12.6, 14.7, 14.8, 14.8, 59.9, 60.7,
14.4, 118.8, 124.6, 128.3, 129.9, 131.7, 134.8, 141.6, 162.3, 165.8,
83.3. m/z 742.9 (dimer as Na adduct). R 0.14.
3 H
) δ 1.35 (3H, t, J ) 7 Hz), 1.38 (3H, t, J ) 7 Hz), 2.22
(
7
3
C
1
1
f
4
-(4-Acetyl-3,5-dimethyl-1H-pyrrole-2-carbonyl)-3,5-di-
methyl-1H-pyrrole-2-carboxylic Acid Ethyl Ester (8). Isola-
tion of the title compound as an off white solid (0.099 g, 63%).
Supporting Information Available: General experiment
Mp 256-257 °C dec. NMR (DMSO-d
) δ
6 H
1.31 (3H, t, J ) 7 Hz),
13
details, characterization data for 4d, and C NMR spectra for
2
.10 (3H, s), 2.16 (3H, s), 2.24 (3H, s), 2.36 (3H, s), 2.46 (3H, s),
.24 (2H, q, J ) 7 Hz), 11.60 (1H, br s), 11.72 (1H, br s); NMR
) δ 11.6, 12.4, 12.7, 14.8, 14.9, 31.7, 59.8, 118.0, 123.1,
24.3, 127.6, 127.8, 129.6, 135.6, 139.6, 161.2, 183.0, 195.0. m/z
82.9 (dimer as Na adduct). R 0.07.
,2′-Bis(3,5-dimethyl-1H-pyrrole-4-carboxylic acid ethyl
ester)carbonyl (9). Isolation of the title compound as an orange
4
b-i, 7, 8, and 9. This material is available free of charge via
4
the Internet at http://pubs.acs.org.
(DMSO-d
6
C
1
6
JO051906W
f
2
(26) Fischer, H.; Orth, H. Liebigs. Ann. Chem. 1931, 489, 62-86.
10610 J. Org. Chem., Vol. 70, No. 25, 2005