Convenient one-pot synthesis of N-substituted 3-trifluoroacetyl pyrroles

Article abstract of DOI:10.1055/s-0028-1087821

A new one-pot strategy for the synthesis of a series of new N-substituted 3-trifluoroacetyl pyrroles is presented. These compounds were obtained by the reaction of 3-trifluoroacetyl-4,5-dihydrofuran with primary amines, which generated 1,1,1-trifluoro-3-(2-hydroxyethyl)-4-alkylaminobut-3-en-2-one intermediates. In most cases these intermediates were not stable enough to be isolated. Thus, in the same reaction vessel they were directly submitted to oxidation with PCC (Corey's reagent) to furnish 1,1,1-trifluoro-3-(2-ethanal)-4- alkylaminobut-3-en-2-ones, which under reflux underwent intramolecular cyclization to give the desired N-substituted 3-trifluoroacetyl pyrroles, in moderate yields. All of these pyrroles were tested against pan-susceptible Mycobacterium tuberculosis H37Rv and clinical isolates INH- and RMP-resistant strain and some of these compounds showed significant in vitro antimicrobial activity. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-0028-1087821

LETTER
755
Convenient One-Pot Synthesis of N-Substituted 3-Trifluoroacetyl Pyrroles
Synthesis of
N
-Sub
i
stitute
l
d 3-Tr
i
o
fluoroacetyl Pyrrol
Z
es anatta,*a Ana D. Wouters,a Leonardo Fantinel,a Fabio M. da Silva,a Rosemário Barichello,a
Pedro E. A. da Silva,b Daniela F. Ramos,b Helio G. Bonacorso,a Marcos A. P. Martinsa
a
Núcleo de Química de Heterociclos (NUQUIMHE), Departamento de Química, Universidade Federal de Santa Maria,
97105-900 Santa Maria, Brazil
Fax +55(55)32208756; E-mail: zanatta@base.ufsm.br
Departamento de Patologia, Fundação Universidade Federal de Rio Grande, Rio Grande, RS, Brazil
b
Received 1 December 2008
unsaturated trifluoromethyl ketones, and intramolecular
cyclization of trifluoro(dimethoxyethylamino)alken-
ones.13 More specifically, the synthesis of 3-trifluoro-
acetyl pyrroles are much less reported and very few of
Abstract: A new one-pot strategy for the synthesis of a series of
new N-substituted 3-trifluoroacetyl pyrroles is presented. These
compounds were obtained by the reaction of 3-trifluoroacetyl-4,5-
dihydrofuran with primary amines, which generated 1,1,1-trifluoro-
3-(2-hydroxyethyl)-4-alkylaminobut-3-en-2-one intermediates. In them are N-substituted.7a,13
most cases these intermediates were not stable enough to be isolat-
It is widely known that 2- or 5-substituted pyrroles are
ed. Thus, in the same reaction vessel they were directly submitted
to oxidation with PCC (Corey’s reagent) to furnish 1,1,1-trifluoro-
3-(2-ethanal)-4-alkylaminobut-3-en-2-ones, which under reflux un-
derwent intramolecular cyclization to give the desired N-substituted
3-trifluoroacetyl pyrroles, in moderate yields. All of these pyrroles
were tested against pan-susceptible Mycobacterium tuberculosis
H37Rv and clinical isolates INH- and RMP-resistant strain and
some of these compounds showed significant in vitro antimicrobial
activity.
easily synthesized by aromatic electrophilic substitu-
tion,14 whereas a special strategy is necessary to obtain 3-
or 4-substituted pyrroles.15 In addition, the introduction of
N-substituents in pyrroles is a difficult task because N-
alkylation competes with C-alkylation.16 Therefore, it is
important to note that there is a clear demand for the de-
velopment of a modular and simple reaction to strategical-
ly access 3-substituted as well as N-substituted pyrroles.17
Trifluoromethyl-containing pyrroles are relatively rare,
however, some of these compounds have demonstrated
important insecticidal action and mitochondrial uncou-
pling activity.18
Key words: pyrroles, 3-trifluoroacetylpyrroles, dihydrofuran, N-
substituted pyrroles, antimicrobial activity
Pyrroles are among the most important heterocycles due
both to their wide distribution in nature and to the fact that
they comprise the structure of numerous synthetic com-
pounds with significant pharmacological activities.1 In
addition, pyrroles are the main scaffold of biologically
important molecules such as, chlorophyll, hemoglobin,
and vitamin B12.2
In this paper, we wish to report a new, simple, and highly
chemoselective one-pot method to synthesize N-substitut-
ed 3-trifluoroacetylpyrroles from the reaction of 3-trifluo-
roacetyl-4,5-dihydrofuran and primary amines, followed
by an in situ oxidation with PCC and intramolecular cy-
clization (Scheme 1). To the best of our knowledge, no
description of such a procedure has been reported for the
synthesis of the title pyrroles. In addition, all the pyrroles
obtained in this study are new and their in vitro antimicro-
bial activity was tested against pan-susceptible Mycobac-
terium tuberculosis H37Rv and clinical isolates INH and
RMP-resistant strains.19
The presence of a pyrrole residue in important drugs such
as Lipitor®, a cholesterol-lowering agent;3 Chloripac® and
Keterolac®, potent nonsteroidal anti-inflammatory
agents;4 and Netropsin® and Distamicin®,5 antibiotics
with a wide range of antimicrobial activity, has consider-
ably increased interest in pyrrole chemistry in recent
years.
O
O
O
The two most widespread methods to introduce a trifluo-
roacetyl group in heterocycles is by direct trifluoro-
acetylation6 and through a cyclocondensation reaction of
a bis(trifluoroacetyl)vinyl ether7 and -amines8 with dinu-
cleophiles. Other methods include oxidative dimerization
of 1,1,1-trifluoro-4-arylbut-3-yn-2-one, carried out by
treatment of lead dioxide in a CH2Cl2–TFA mixture,9 di-
polar cycloaddition of diazo compounds10 and azides11
with a,b-unsaturated trifluoromethyl ketones,12 photoin-
duced cyclization of sulfimino uracil substituted with a,b-
F3C
NHR
b
CF3
a
F3C
H
NHR
O
OH
O
4a–u
3a–u
1
c
d
O
O
CF3
F3C
NHR
N
R
5a–u
SYNLETT 2009, No. 5, pp 0755–0758
Advanced online publication: 24.02.2009
DOI: 10.1055/s-0028-1087821; Art ID: S12108ST
x
x.
x
x.
2
0
0
9
Scheme 1 Reaction conditions: (a) RNH2 (2a–u), CH2Cl2, 0.5 h,
r.t., (b) PCC, CH2Cl2; (c) reflux, 3 h; (d) spontaneous conversion.
© Georg Thieme Verlag Stuttgart · New York

756
N. Zanatta et al.
LETTER
Scheme 1 outlines the synthetic strategy used to synthe- umn chromatography using basic alumina as the station-
size the N-substituted 3-trifluoroacetylpyrroles. The 3-tri- ary phase and ethyl ether as the eluant.26
fluoroacetyl-4,5-dihydrofuran (1) was prepared according
Under the reaction conditions reported in this study,
aniline and arylamines, such as 3-hydroxy-4-methyl-
aniline, 2-hydroxy-4-methylaniline, 2-chloro-aniline, 2,4-
dichloroaniline, and 4-fluoroaniline, failed to react with 3-
to the literature.20 The reaction of compound 1 with pri-
mary amines 2a–r (1 equiv) and amines 2s–u (0.5 equiv),
in dichloromethane, furnished the enamino alcohols 3,
which were oxidized in situ with pyridinium chlorochro-
trifluoroacetyl-4,5-dihydrofuran (1). Additionally, reac-
mate (PCC)21 to generate the corresponding aldehydes 4.
tions of 3-trichloroacetyl-4,5-dihydrofuran with amines
These aldehydes underwent cyclization to give the pyr-
roles 5a–r and the bispyrrole compounds 5s–u, in moder-
furnished 3-aminomethylenedihydrofuran-2-ones27 in-
stead of N-substituted 3-trifluoroacetyl pyrroles. All pyr-
ate yields. The relative low overall yields (20–56%) were
roles obtained in this study were tested for their
probably due to the difficulty to isolate the pyrroles from
antimycobacterial activity. Four of these pyrroles
the oxidation medium22 and the partial solubility of these
Table 1 Optimized Reaction Conditions for the Synthesis of 5a–u
compounds in water. However, if one considers that these
are overall yields of a three-step reaction, they may not be
O
O
considered so low (Table 1). In order to improve yields,
other oxidants such as pyridinium dichromate (PDC)23
and pyridinium fluorochromate (PFC)24 were used, but
both furnished the desired products in lower yields than
the PCC method.
(a) RNH2 (2a–u), CH2Cl2, 0.5 h, r.t.
CF3
CF3
(b) PCC, CH2Cl2, reflux, 3 h
O
N
R
5a–u
1
Entry
1
Compd Amine 2a–ua
Yield (%)b Product
During the development of this study, many efforts were
taken to isolate the alcohol intermediates 3. In fact, many
of these alcohol intermediates were isolated, however,
they were relatively unstable as they slowly decomposed
to the corresponding trifluoroacetamides (Scheme 1). The
spontaneous conversion of compound 3l to N-benzyltri-
fluoroacetamide was followed by 13C NMR spectroscopy,
where, during the spectral acquisition of compound 3l, for
example, the quartet of the C(O)CF3 (2JCF = 30 Hz), at d =
173.8 ppm tended to decrease in intensity while a signal
of a new quartet appeared at d = 158.7 ppm, which is con-
sistent with the chemical shift of a carbonyl of a trifluoro-
acetamide. The formation of the N-benzyltri-
fluoroacetamide was also confirmed by GC-MS. To fur-
ther confirm the formation of N-benzyltrifluoroacet-
amide, this compound was synthesized by the reaction of
benzylamine and trifluoroacetic anhydride, which con-
firmed our expectation. Thus, the reactions were carried
out without the isolation of the alcohol intermediate 3.
The formation of alcohols 3 were monitored by TLC and
it was observed that the reaction was completed in ap-
proximately 30 minutes, at room temperature. After this
period, 1.2 equivalents of PCC were added to the reaction
vessel, and the reaction was refluxed for three hours to
give the pyrroles 5 in 20–56% overall yields. The alde-
hydes 4 were not isolated because cyclization began soon
after the addition of PCC, even keeping the reaction at
room temperature. An attempt to isolate aldehydes 4 fur-
nished mixtures of aldehydes 4, alcohols 3, and pyrroles
5. Based on these results, we decided to carry out the
reaction in a one-pot procedure to obtain the final pyrroles
without the isolation of their intermediates (see Table 1
for reaction conditions and yields).25
2ac
2bc
2c
NH4OH
28
36
41
46
52
43
20
45
56
54
41
55
50
5a
5b
5c
5d
5e
5f
2
MeNH2
3
EtNH2
4
2d
2e
PrNH2
5
i-PrNH2
6
2f
allylNH2
7
2g
2h
2i
HO(CH2)2NH2
HO(CH2)3NH2
MeCH(OH)CH2NH2
MeCH2CH(NH2)CH2OH
HOCH2C(CH3)2NH2
BnNH2
5g
5h
5i
8
9
10
11
12
13
14
15
16
17
18
19
20
21
2j
5j
2k
2l
5k
5l
2m
2n
2o
2p
2q
2r
Ph(CH2)2NH2
5m
5n
5o
5p
5q
5r
5s
5t
(pyridin-2-yl)methylamine 47
(pyridin-3-yl)methylamine 51
(pyridin-4-yl)methylamine 39
Me2N(CH2)2NH2
Et2N(CH2)2NH2
H2N(CH2)2NH2
H2N(CH2)3NH2
H2N(CH2)4NH2
25
41
27
46
34
2sd
2td
2ud
5u
a Reaction conditions (except otherwise indicated): 1) amine (1
equiv), CH2Cl2, 30 min, r.t.; 2) PCC (1.2 equiv), 3 h, reflux.
b Yields after purification by column chromatography.
c In aqueous solution. Amine was used in excess and the alcohol 3 was
extracted with CH2Cl2 before reaction with PCC.
d Amine used: 0.5 equiv.
Reaction products 5 were isolated by the evaporation of
dichloromethane from the reaction mixture and the re-
maining black residue was dissolved in a 1 M solution of
sodium hydroxide and the alkaline solution was extracted
with ethyl ether. Compounds 5a–u were purified by col-
Synlett 2009, No. 5, 755–758 © Thieme Stuttgart · New York

LETTER
Synthesis of N-Substituted 3-Trifluoroacetyl Pyrroles
757
(5f,h,l,m) showed significant in vitro antimycobacterial
activity against pan-susceptible Mycobacterium tubercu-
losis H37Rv and clinical isolates isoniazid (INHr) and
rifampin (RMPr) resistant strains.19
O
O
HO
CF3
CF3
F3C
NHR
RNH2
O
NHR
O
H
2a–u
The intermediates 3 and 4 (Scheme 1) may exist in both Z-
and E-isomers, as shown in Scheme 2, by structures I and
II, respectively. The mechanism that such interconversion
may occur is represented by structures III, IV, and V. The
formation of the intermediate I (Z-isomer) is preferred in
nonpolar or low polar solvents, such as chloroform, due to
the hydrogen-bond formation between the N–H and the
carbonyl. In high polar solvents, such as DMSO, structure
II may be more favorable. Structure I has a wrong stereo-
chemistry for intramolecular cyclization, however, a low
energy barrier of the carbon–carbon double bond of the
enaminone III, driven by the push–pull effect of the car-
bonyl (p-acceptor) and the b-amino group (p-donor) al-
lows easy rotation around this bond as shown by
structures IV and V.28 Thus, because of the easy intercon-
version between the E- and Z-isomers (structures IV and
V), the aldehyde intermediates 4 can be completely con-
verted into the corresponding pyrroles 5 regardless of the
configuration of the carbon–carbon double bond.
OH
1
VI
VII
O
O
O
H
CF3
CF3
PCC
F3C
H
NHR
– H2O
HO
N
R
N
R
O
XIV
VIII
5a–u
Scheme 3
introduction of a large scope of N-substituents to the pyr-
role ring, especially hydroxylated substituents without
protection of the hydroxyl function. Furthermore, this
study showed that 3-trifluoroacetyl-4,5-dihydrofuran is a
convenient reagent for the synthesis of the title pyrroles,
since it is obtained easily and in excellent yield through
the trifluoroacetylation of the commercially available 4,5-
dihydrofuran. Compounds 5f,h,l,m showed significant in
vitro antimycobacterial activity against pan-susceptible
Mycobacterium tuberculosis (H37Rv) and clinical isolates
isoniazid (INHr) and rifampin (RMPr) resistant strains.
H
R
O
O
N
F3C
NHR
F3C
Acknowledgment
X
X
I
II
The authors thank the financial support from the Conselho Nacional
de Desenvolvimento Científico e Tecnológico (CNPq – Universal
grant No. 476634/06-7), and fellowships from CAPES (A. D.
Wouters, L. Fantinel and F. M. da Silva).
O
X
NHR
O–
N+HR
O–
N+HR
F3C
H
F3C
F3C
References and Notes
X
IV
X
(1) Morales, G. O.; Méndez, F.; Miranda, D. L. Tetrahedron
Lett. 2007, 48, 4515.
III
V
(2) Das, B.; Chowdhury, N.; Damodar, K. Tetrahedron Lett.
2007, 48, 2867.
X = OH, CHO
(3) Misra, N. C.; Panda, K.; Ila, H.; Junjappa, H. J. Org. Chem.
2007, 72, 1246.
Scheme 2
(4) Pridmore, S. J.; Slatford, P. A.; Aurélie, D.; Whittlesey,
M. K.; Williams, J. M. J. Tetrahedron Lett. 2007, 48, 5115.
(5) Marcotte, F. A.; Lubell, W. D. Org. Lett. 2002, 4, 2601.
(6) (a) Kawase, M.; Hirabayashi, M.; Koiwai, H.; Yamamoto,
K.; Miyamae, H. Chem. Commun. 1998, 641. (b) Bray,
B. L.; Mathies, P. M.; Naef, R. N.; Solas, D. R.; Tidwell,
T. T.; Artis, D. R.; Muchowski, J. M. J. Org. Chem. 1990,
55, 6317. (c) Wynne, J. H.; Lloyd, C. T.; Jensen, S. D.;
Boson, S.; Stalick, W. M. Synthesis 2004, 2277.
(7) (a) Okada, E.; Masuda, R.; Hojo, M. Heterocycles 1992, 34,
791. (b) Druzhinin, S. V.; Balenkova, E. S.; Nenajdenko,
V. G. Tetrahedron 2007, 63, 7753.
(8) (a) Andrew, R. J.; Mellor, J. M. Tetrahedron 2000, 56,
7267. (b) Okada, E.; Kinomura, T.; Takeuchi, H.; Hojo, M.
Heterocycles 1997, 44, 349. (c) Soufyane, M.; Mirand, C.;
Levy, J. Tetrahedron Lett. 1993, 34, 7737.
(9) (a) Rudenko, A. P.; Aristov, S. A.; Vasilyev, A. V. Russ.
J. Org. Chem. 2004, 40, 1221. (b) Aristov, S. A.; Vasilyev,
A. V.; Rudenko, A. P. Russ. J. Org. Chem. 2006, 42, 66.
The mechanism of formation of pyrroles 5 begins with the
Michael addition of the amine nitrogen at the b-carbonyl
position of 3-trifluoroacetyl-4,5-dihydrofuran 1 to give
structure VI (Scheme 3), which, upon restoring the carbo-
nyl, opens the furan ring to give the enamino ketone VII.
Oxidation of VII with PCC affords the aldehyde VIII,
which undergoes intramolecular cyclization leading to
structure XIV, which eliminates a water molecule to fur-
nish the N-substituted 3-trifluoroacetyl pyrroles 5a–u.
In summary, we have developed a simple and efficient
one-pot procedure for the preparation of new N-substitut-
ed 3-trifluoroacetyl pyrroles, using mild reaction condi-
tions and leading to relatively good overall yields if one
considers that a three-step reaction is carried out in the
same reaction vessel. In addition, this method allows the
Synlett 2009, No. 5, 755–758 © Thieme Stuttgart · New York

758
N. Zanatta et al.
LETTER
(10) Nenajdenko, V. G.; Statsuk, A. V.; Balenkova, E. S. Chem.
Heterocycl. Compd. 2003, 5, 598.
(11) Peng, W.-M.; Zhu, S.-Z. J. Fluorine Chem. 2002, 116, 81.
(12) Matsumoto, N.; Takahashi, M. Tetrahedron Lett. 2005, 46,
5551.
(25) Synthesis of N-Substituted 3-Trifluoroacetyl Pyrroles 5 –
General Procedure
To a solution of 3-trifluoroacetyl-4,5-dihydrofuran 1 (0.50 g,
3.0 mmol) in CH2Cl2 (5 mL), amines 2a,b (approx. 6.0
mmol), amines 2c–r (3.0 mmol), and amines 2s–u (1.5
mmol) were added under magnetic stirring, and the reaction
was stirred for 30 min at r.t. After this period, PCC (4.5
mmol) in CH2Cl2 (5 mL) was added, and the reaction
mixture was refluxed for 3 h. For amines 2a,b, before the
addition of PCC, the reaction was extracted with CH2Cl2
(3 × 15 mL) and dried with MgSO4. The solvent was
evaporated by rotary evaporator, and the reaction residue
was treated with 1 M solution of NaOH and extracted with
Et2O (3 × 50 mL). The combined organic layers were
washed with 1 M NaOH solution (2 × 50 mL) and distilled
H2O (1 × 50 mL). The organic phase was dried with anhyd
MgSO4, evaporated, and purified by column
(13) (a) Okada, E.; Masuda, R.; Hojo, M.; Yoshida, R.
Heterocycles 1992, 34, 1435. (b) Elguero, R.; Jacquier, B.;
Shimizu, B. Bull. Soc. Chim. Fr. 1967, 2996. (c) Elguero,
R.; Jacquier, B.; Shimizu, B. Bull. Soc. Chim. Fr. 1970,
1585. (d) Shaitanova, E. N.; Gerus, I. I.; Kukhar, V. P.
Tetrahedron Lett. 2008, 49, 1184.
(14) Jones, R. A.; Bean, G. P. In The Chemistry of Pyrroles;
Academic Press: London, 1977 and references cited therein.
(15) (a) Pavri, N. P.; Trudell, M. L. J. Org. Chem. 1997, 62,
2649. (b) Chen, N.; Lu, Y.; Gadamasetti, K.; Hurt, C. R.;
Norman, M. H.; Fotsch, C. J. Org. Chem. 2000, 65, 2603.
(c) Marcotte, F.-A.; Rombouts, F. J. R.; Lubell, W. D.
J. Org. Chem. 2003, 68, 6984. (d) Kagoshima, H.;
Akiyama, T. J. Am. Chem. Soc. 2000, 122, 11741.
(e) Wasserman, H. H.; Power, P.; Petersen, A. K.
Tetrahedron Lett. 1996, 37, 6657.
chromatography using basic alumina (60 g) with a plug of
active charcoal and eluted with Et2O (50 mL).
(26) Spectroscopic Data of Selected Compounds
1-Methyl-3-trifluoroacetylpyrrole (5b)
(16) (a) Nunomoto, S.; Kawakami, Y.; Yamashita, Y.; Takeuchi,
H.; Egushi, S. J. Chem. Soc., Perkin Trans. 1 1990, 111.
(b) Bourak, M.; Gallo, R. Heterocycles 1990, 31, 401.
(17) For recent examples, see: (a) Salamone, S. G.; Dudley,
G. B. Org. Lett. 2005, 7, 4443. (b) Song, G.; Wang, B.;
Wang, G.; Kang, Y.; Yang, T.; Yang, L. Synth. Commun.
2005, 35, 1051. (c) Dieltiens, N.; Stevens, C. V.; De Vos,
D.; Allaert, B.; Drozdzak, R.; Verpoort, F. Tetrahedron Lett.
2004, 45, 8995. (d) Tracey, M. R.; Hsung, R. P.; Lambert,
R. H. Synthesis 2004, 918. (e) Wang, B.; Gu, Y.; Luo, C.;
Yang, T.; Yang, L.; Suo, J. Tetrahedron Lett. 2004, 45,
3417. (f) Dhawan, R.; Arndtsen, B. A. J. Am. Chem. Soc.
2004, 126, 468. (g) Abdelrazek, F. Synth. Commun. 2005,
35, 2251. (h) Delayen, A.; Goossens, L.; Houssin, R.;
Henichart, J. P. Heterocycles 2005, 65, 1673.
1H NMR (200 MHz, CDCl3): d = 7.4 (s, 1 H), 6.7 (s, 1 H),
6.6 (s, 1 H), 3.7 (s, 1 H). 13C NMR (100 MHz, CDCl3):
d = 175.0 (q, 2JCF = 35.3 Hz), 130.1, 124.3, 117.8, 116.9 (q,
1JCF = 288.7 Hz), 110.9, 36.8. GC-MS (IE, 70eV): m/z (%) =
117 (68) [M+], 108 (100), 80 (30). ESI-HRMS: m/z calcd for
C6H4F3NO [M + H]+: 178.0479; found: 178.0471.
1-(Ethan-1-ol-2-yl)-3-trifluoroacetylpyrrole (5g)
1H NMR (400 MHz, CDCl3): d = 7.5 (s, 1 H), 6.7 (m, 2 H),
4 (t, 1 H, J = 9.2 Hz), 3.9 (t, 1 H, J = 9.2 Hz). 13C NMR (100
MHz, CDCl3): d = 175.4 (q, 2JCF = 35.7 Hz), 130.1, 123.8,
117.8, 116.9 (q, 1JCF = 288.8 Hz), 110.9, 61.8, 52.5. GC-MS
(IE, 70eV): m/z (%) = 207 (25) [M+], 138 (100), 94 (57).
ESI-HRMS: m/z calcd for C9H8F3NO [M + H]+: 208.0585;
found: 208.0576.
1-(2,2-Dimethyl-etan-1-ol-2-yl)-3-trifluoroacetylpyrrole
(5k)
(18) Black, B. C.; Hollingworth, R. M.; Ahammadsahib, K. Y.;
Kukel, C. D.; Donovan, S. Pestic. Biochem. Physiol. 1994,
50, 115.
1H NMR (400 MHz, CDCl3): d = 7.6 (s, 1 H), 6.9 (m, 1 H),
6.7 (m, 2 H), 3.6 (s, 2 H), 1.5 (s, 6 H). 13C NMR (100 MHz,
CDCl3): d = 175.4 (q, 2JCF = 35 Hz), 127.5, 121, 117.3,
116.9 (q, 1JCF = 289 Hz), 110.5, 70.4, 60.2, 24.5. GC-MS (IE
70eV): m/z (%) = 235 (30) [M+], 204 (97), 94 (100). ESI-
HRMS: m/z calcd for C10H12F3NO2 [M + H]+: 236.0898;
found: 236.0891.
(19) Unpublished results: compound 5f exhibited activity against
H37Rv and RMPr (MIC = 12.5 mg/mL) and INHr (MIC = 50
mg/mL); 5h exhibited activity against H37Rv and RMPr
(MIC = 12.5 mg/mL) and INHr (MIC = 25.0 mg/mL); 5l
exhibited activity against H37Rv (MIC = 6.25 mg/mL) and
RMPr and INHr (MIC = 12.5 mg/mL); 5m exhibited activity
against H37Rv and RMPr (MIC = 6.25 mg/mL) and INHr
(MIC = 12.5 mg/mL).
1-(Ethan-2-dimethylamino-1-yl)-3-trifluoroacetyl-
pyrrole (5q)
1H NMR (400 MHz, CDCl3): d = 7.55 (s, 1 H), 6.74 (m, 2
H), 4.01 (t, 2 H, J = 3.2 Hz) 2.67 (t, 2 H, J = 3.1 Hz), 2.27 (s,
6 H). 13C NMR (100 MHz, CDCl3): d = 175.2 (q, 2JCF = 35
Hz), 129.6, 123.5, 117.8, 116.9 (q, 1JCF = 288 Hz), 110.7,
59.6, 48.5, 45.4. GC-MS (IE, 70eV): m/z (%) = 235 (100)
[MH+], 165 (20). ESI-HRMS: m/z calcd for C10H13F3N2O
[M + H]+: 235.1058; found: 235.1058.
(20) Colla, A.; Martins, M. A. P.; Clar, G.; Krimmer, S.; Fisher,
P. Synthesis 1991, 483.
(21) (a) Corey, E. J.; Sugs, J. W. Tetrahedron Lett. 1975, 32,
2647. (b) Hunsen, M. Tetrahedron Lett. 2005, 46, 1651.
(c) Dugger, R. W.; Ragan, J. A.; Brown, D. H. Org. Process
Res. Dev. 2005, 9, 253. (d) Rauter, A. D.; Piedade, F.;
Almeida, T.; Ramalho, R.; Ferreira, M. J.; Resende, R.;
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M.; Canda, T. Carbohydr. Res. 2004, 339, 1889. (e) Li,
S. H.; Li, T. S. Steroids 1998, 63, 76. (f) Rauter, A. P.;
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1,2-Bis-3-trifluoroacetylpyrrole-1-yl-ethane (5s)
1H NMR (400 MHz, CDCl3): d = 7.14 (s, 1 H), 6.77 (s, 1 H),
6.50 (m, 1 H), 4.30 (s, 2 H). 13C NMR (100 MHz, CDCl3):
d = 175.2 (q, 2JCF = 35 Hz), 128.8, 122.8, 118.8, 116.7 (q,
1JCF = 288 Hz), 111.9, 52.1. GC-MS (IE, 70eV): m/z (%) =
352 (31) [M+], 283 (100), 176 (26), 107 (25). ESI-HRMS:
m/z calcd for C14H10F6N2O2 [M + H]+: 367.0881; found:
367.0876.
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Synlett 2009, No. 5, 755–758 © Thieme Stuttgart · New York

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