Synthesis and anti-staphylococcal activity of new halogenated pyrroles related to pyrrolomycins F

Article abstract of DOI:10.1002/jhet.5570440626

(Chemical Equation Presented) The chemical synthesis of new halogenated pyrroles related to pyrrolomycins F is described and the anti-staphylococcal activity compared. The replacement of 4′-bromo atom of parent compounds with two chloro atoms at 3′ and 5′

Full text of DOI:10.1002/jhet.5570440626

Nov-Dec 2007
1407
Synthesis and Anti-Staphylococcal Activity of New Halogenated
Pyrroles Related to Pyrrolomycins F
Maria Valeria Raimondi*, Domenico Schillaci and Salvatore Petruso
Dipartimento di Chimica e Tecnologie Farmaceutiche, Università degli Studi di Palermo, Via Archirafi 32,
90123 Palermo, Italy
*Corresponding author. Tel. +39 091 6236115; fax +39 091 6236119, e-mail address: mvraimondi@unipa.it
Received January 11, 2007
Cl
Cl
Br
Br
Cl
Br
Br
N
H
Br
N
H
Cl
Cl
O
O
HO
HO
2
3
Cl
Cl
Cl
Br
Br
Br
Cl
N
H
Cl
N
Cl
O
Cl
O
HO
H
HO
4
5
The chemical synthesis of new halogenated pyrroles related to pyrrolomycins F is described
and the anti-staphylococcal activity compared. The replacement of 4'-bromo atom of parent
compounds with two chloro atoms at 3' and 5' position increase the antibacterial activity against
a reference strain of S. aureus.
J. Heterocyclic Chem., 44, 1407 (2007).
interesting resource of new antibiotics is represented by
some natural halogenated pyrroles, known as pyrrolomycins
(Figure 1). Such molecules, isolated from culture broth of
Actinosporangium vitaminophilum SF-2080 [2-5], have a
good activity especially against Gram-positive bacteria, in
particular Staphylococcus aureus.
INTRODUCTION
Antibiotic resistance of important Gram-positive
pathogens as Staphylococcus aureus, is currently a
significant global health problem. The overuse of
antibiotics, both in human and animal population, played an
important role in the beginning of drug-resistant strains.
Furthermore, bacteria can survive and thrive in hostile
environments, forming, on living and nonliving surfaces, as
indwelling medical devices, organized communities of
bacterial cells (biofilms), that are difficult or impossible to
treat with conventional antibiotics [1]. There is an urgent
need to develop new agents against these pathogens and an
A different group of pyrrolomycins, generically named
PM-F, has been produced from A. vitaminophilum SF-
2080 when bromide ion was added to the fermentation
medium [6] (Figure 2).
Br
Br
Br
Br
Cl
Br
Br
N
H
Br
N
H
O
Cl
O
Cl
Cl
HO
HO
Cl
NO2
Cl
NO2
PM-F1
PM-F2a
Cl
N
H
Cl
N
H
Cl
N
H
Cl
O
Cl
HO
HO
Br
Br
Br
Cl
Br
Br
PMA
PMC
PMB
NO2
Cl
Cl
N
Cl
N
Cl
Cl
O
O
Cl
H
H
HO
HO
Cl
N
H
PM-F2b
PM-F3
Cl
N
H
Cl
O
HO
HO
Cl
Figure 2
PMD
PME
Some PM-F components possessed equal or more
potent activity, against some Gram-positive bacteria, than
Figure 1

1408
M. V. Raimondi, D. Schillaci and S. Petruso
Vol 44
PM-D, the most active component among PM-A to E [6].
We have previously described the synthesis of some
brominated pyrrolomycin analogs [7] and their activity
against antibiotic sensitive and resistant S. aureus clinical
strains [8]. The most active member of this series, the
3,4,5,3',5'-pentabromo-2-(2'-hydroxybenzoyl)pyrrole 1
(Figure 3), bromo analog of pyrrolomycin D and strictly
related to pyrrolomycin F1, exhibited an interesting
activity against S.aureus ATCC 25923 and promising
effects against preformed Staphylococcus epidermidis and
S. aureus biofilms [9].
dichloromethane at room temperature, afforded to the 2'-
hydroxy derivative 2 in excellent yield (Scheme 1).
Scheme 1
Cl
Cl
Br
Br
NBS, 3 eq.
CH3CN
Cl
Cl
Br
N
H
N
H
O
OMe
O
OMe
6
7
AlCl3
Br
Cl
Br
Br
Br
Br
Br
Br
Cl
N
H
Br
N
H
O
OH
O
OH
1
2
Figure 3
The reaction of 6 with one molar equivalent of N-
chlorosuccinimide (NCS) gave a trichloroderivative to
whom the structure 8 was assigned on the basis of 1H nmr
spectrum. In fact this compound exhibit two doublets at
6.64 and 7.42 ꢀ (j=1.5 Hz) unequivocally attributable to
On the basis of the known importance of electron
attractive effect of substituents on the phenolic ring on the
antibacterial activity of monodeoxypyoluteorin [10], we
investigated if the introduction of chloro atoms in 3,5-
positions of phenolic ring of F pyrrolomycins could
improve the antibacterial activity of this class of
compounds. For this purpose we synthesized the
compounds 2-5 (Fig. 4), whose phenolic moiety was
identical to that of pyrrolomycins B-E, and we evaluated
their anti-staphylococcal activity against S.aureus ATCC
25923.
Scheme 2
Cl
Cl
N
O
OMe
H
6
Cl
2: R1 = R2 = Br
R2
Br
3: R1 = Br, R2 = Cl
4: R1 = Cl, R2 = Br
5: R1 = R2 = Cl
NCS, 1 eq.
Cl
NCS, 2 eq.
R1
Cl
N
H
Cl
O
OH
Cl
Cl
Cl
Cl
N
H
Figure 4
Cl
N
H
O
OMe
O
OMe
9
8
RESULTS AND DISCUSSION
NBS, 1 eq.
Cl
NBS, 2 eq.
The molecular skeleton of 2 was assembled by
allowing pyrrylmagnesium bromide to react with 3,5-
dichloro-2-methoxybenzoyl chloride according to
procedures previously reported by Davies and Hodge for
the synthesis of 2-(2',6'-dimethoxybenzoyl)pyrrole [11].
The 3',5'-dichloro-2-(2'-methoxybenzoyl)pyrrole 6, so
obtained, was purified by column chromatography. The
subsequent halogenation of compound 6, was carried out
using N-bromosuccinimide (NBS) or N-chlorosuccin-
imide (NCS) in acetonitrile as previously described [12-
13]; so the bromination of 6 using three molar equivalents
of NBS afforded the 3,4,5-tribromoderivative 7.
Demethylation of 7 with aluminium chloride in anhydrous
Cl
Br
Cl
Cl
Br
Cl
Br
Cl
N
Cl
N
H
O
OMe
H
O
OMe
Cl
11
10
AlCl3
AlCl3
Cl
Cl
Br
Cl
Br
Br
Cl
Cl
N
H
Cl
N
H
O
OH
O
OH
3
5

Nov-Dec 2007
Synthesis and Anti-Staphylococcal Activity of New Halogenated Pyrroles
Related to Pyrrolomycins F
1409
H-3 and H-5 protons respectively of pyrrolic ring. The
unusual chemical shift of 3-proton, more shielded than
that expected from 2-carbonyl pyrroles, was due to the
anisotropic effect of phenyl ring, twisted with respect to
the plane of pyrrolic ring. According to what previously
observed by P. Hodge and R. W. Rickards [14], the
introduction of chlorine (or bromine) substituents into
pyrrole rings cause only minor shifts in the resonance
frequencies of the remaining hydrogens. On the contrary,
the reaction of 8 with two molar equivalent of NCS gave
the 4,5-dichloroderivative 9 (chemical shift for H-3 = 6.84
ꢀ) which was brominated with NBS to give 11 whose
demethylation with aluminium chloride afforded to 5 in
excellent yield (Scheme 2).
The results of antibacterial screening, expressed as
minimum inhibitory concentration (mic), are reported in
Table 1.
Table 1
Antibacterial Activity (mic/μg per ml)
Compound
Pyrrolomycin F1
Pyrrolomycin F2a
Pyrrolomycin F2b
S. aureus ATCC 25923
0.02
0.005
0.01
Pyrrolomycin F3
Pyrrolomycin C
0.02
0.18
Pyrrolomycin D
Vancomycin
ꢀ 0.001
1.0
1
2
3
4
5
0.005
ꢀ 0.001
ꢀ 0.001
ꢀ 0.001
ꢀ 0.001
Compound 4 was synthesized from 6, which was
brominated at 4-position (H-3 and H-5 at 6.69 and 7.43
ꢀ respectively) using one molar equivalent of NBS
(Scheme 3).
CONCLUSIONS
Scheme 3
Cl
The results of antibacterial screening showed that the
introduction of two chloro atoms at 3' and 5' positions of
phenolic ring carried to an increase of activity. All new
pyrrolomycins analogs synthesized were in fact more
active than pyrrolomycin F2a, the most active member of
PM-F, to inhibit the staphylococcal growth. The in vitro
activity against S. aureus ATCC 25923 of new
compounds is comparable to that of PM-D that, against
this strain, showed more potent activity than PM-F
components. Moreover, we are going to test the activity of
new compounds against a wide panel of Gram-positive
strains and against preformed biofilms of staphylococci.
Cl
Br
NBS, 1 eq.
Cl
N
H
Cl
N
H
O
OMe
O
OMe
12
6
NCS, 1 eq.
Cl
Cl
Br
Br
Br
NBS, 1 eq.
Cl
Cl
Cl
Cl
N
N
H
O
OMe
O
OMe
H
13
14
AlCl3
EXPERIMENTAL
Cl
Br
Br
Melting points were determined on a Büchi-Tottoli micro
melting point apparatus and are uncorrected. The ir spectra were
recorded at room temperature in Nujol mulls with a Perkin
Cl
Cl
N
O
OH
1
H
Elmer Infrared 137 E spectrometer. The H-nmr spectra were
4
recorded at room temperature on a Bruker SF 250 spectrometer
in DMSO-d6, unless otherwise specified, using tetramethylsilane
as the internal standard. Microanalyses (C, H, N) were carried
out with Elemental Vario EL III apparatus and were in
agreement with theoretical values ± 0.4%.
Chromatographic separations were carried out on columns
packed with Macherey Nagel Kieselgel 60 (70-230 mesh
ASTM). All reactions were monitored by tlc on precoated
aluminium sheets 20 x 20 (0.2 mm Kieselgel 60 G F254, Merck)
and C-18 reverse phase (RP-18 F254, Merk) using UV light at
254 nm for visualization. All reagents and solvents were from
Aldrich, Fluka, Merk or J.T.Baker.
All the compounds were tested for their in vitro growth
inhibitory activity against Staphylococcus aureus ATCC 25923.
PM-D and vancomycin were used for comparative purposes and
quality control of the methods. MICs against bacterial strains
were determined using the broth dilution micro-method as
described [6].
The 4-bromo-3',5'-dichloro-2-(2'-methoxybenzoyl)
pyrrole 12, was chlorinated at 5-position (H-3 at 6.81
ꢀ) with one molar equivalent of NCS, to give 13 which
was in turn brominated at 3-position with NBS. The
subsequent demethylation of compound 14, so
obtained, gave 4.
The structures of all the newly prepared compounds
were confirmed by analytical and spectroscopic data.
According to the procedures just described, the
already known pyrrolomycins F1, F2a, F2b, F3 and D were
prepared and their antibacterial activity toward S. aureus
ATCC 25923 was compared with that of new synthesized
derivatives. Vancomicin, penta-bromo derivative 1, PM-C
and PM-D were also used as standards.

1410
M. V. Raimondi, D. Schillaci and S. Petruso
Vol 44
81% yield) as white crystals, m.p.175-176°C. 1H nmr: ꢀ 3.70 (s,
3H, CH3), 7.53 (d, 1H, J = 2.5 Hz, H-6'), 7.84 (d, 1H, J = 2.5 Hz,
H-4'), 13.68 (br s, 1H, exchangeable with D2O, NH); ir: ꢁ 3213
(NH), 1618 (CO) cm-1. Anal. Calc. (Found) for C12H6Br2Cl3NO2:
C, 31.17% (31.29%); H, 1.31% (1.36%); N, 3.03% (2.98%).
4,5,3',5'-Tetrachloro-2-(2'-methoxybenzoyl)pyrrole (9). To
a stirred solution of 2.70 g (10.0 mmoles) of compound 6 in
acetonitrile (100 ml), 2.70 g (20.0 mmoles) of solid NCS were
added. After 24 hours the mixture was evaporated. The residue
was partitioned between water (100 ml) and diethyl ether (100
ml). The aqueous layer was separated and extracted with diethyl
ether (2 x 50 ml). The combined extracts were washed with
water, dried over anhydrous sodium sulfate and evaporated. The
crude product was crystallized from acetonitrile to give 9 (2.30
g, 68% yield ) as white crystals, m.p. 139-140°C; 1H nmr: ꢀ 3.70
(s, 3H, CH3), 6.84 (s, 1H, H-3),7.57 (d, 1H, J = 2.5 Hz, H-6'),
7.88 (d, 1H, J = 2.5 Hz, H-4'), 13.57 (br s, 1H, exchangeable
with D2O, NH); ir: ꢁ 3219 (NH), 1635 (CO) cm-1. Anal. Calc.
(Found) for C12H7Cl4NO2: C, 42.52% (42.74%); H, 2.08%
(2.21%); N, 4.13% (4.33%).
3',5'-Dichloro-2-(2'-methoxybenzoyl)pyrrole (6). 4.42 g (20
mmoles) of 3,5-dichloro-2-methoxybenzoic acid, commercially
available, and 15 ml (24.50 g, 200 mmoles) of thionyl chloride
were refluxed until the generation of hydrochloric acid ceased
(approximately 8 hours). The excess thionyl chloride was
removed under vacuum and the crude 3,5-dichloro-2-
methoxybenzoyl chloride, dissolved in 100 ml of anhydrous
diethyl ether, was added, dropwise under nitrogen atmosphere,
to a stirred solution of pyrrylmagnesium bromide (20 mmoles in
150 ml of anhydrous diethyl ether). The reaction mixture was
refluxed for 0.5 hours, cooled to room temperature, then
quenched with 10% sulphuric acid (100 ml). After stirring for 1
hour, the ethereal layer was separated and the aqueous phase
extracted with diethyl ether (2 x 100 ml). The combined extracts
were washed with water (2 x 50 ml), dried over anhydrous
sodium sulfate and evaporated. The crude product was purified
by column chromatography using 85/15 (v/v) cyclohexane/ethyl
acetate mixture as eluent to give 3',5'-dichloro-2-(2'-methoxy-
benzoyl)pyrrole (6) (2.75 g, 51% yield), mp 114-115°C (from
1
ethanol) [2]; H nmr: ꢀ 3.72 (s, 3H, CH3), 6.23 (br q, 1H, H-4),
6.56 (br q, 1H, H-3), 7.27 (br q, 1H, H-5), 7.46 (d, 1H, J = 2.3
Hz, H-6'), 7.80 (d, 1H, J = 2.3 Hz, H-4'), 12.23 (br s, 1H,
exchangeable with D2O, NH); ir: ꢁ 3287 (NH), 1636 (CO) cm-1.
Anal. Calc. (Found) for C12H9Cl2NO2: C, 53.36% (53.60%); H,
3.36% (3.24%); N, 5.19% (4.98%).
3-Bromo-4,5,3',5'-tetrachloro-2-(2'-methoxybenzoyl)pyrrole
(11). A solution of 9 (1.70 g, 5.0 mmoles) and NBS (1.78 g, 5.0
mmoles) in 50 ml of acetonitrile was allowed to stand at room
temperature. After 24 hours, the reaction mixture was
evaporated and the residue was purified as described previously
for the preparation of 7. The crude product was crystallized from
3,4,5-Tribromo-3',5'-dichloro-2-(2'-methoxybenzoyl)pyrrole
(7). To a solution of 2.70 g (10.0 mmoles) of 6 in acetonitrile
(50 ml), 5.34 g (30.0 mmoles) of solid NBS were added,
portion-wise under stirring. After 24 hours the reaction mixture
was evaporated under reduced pressure and the residue was
partitioned between water (100 ml) and diethylether (100 ml)
and, subsequently, extracted twice with diethyl ether (100 ml).
The combined extracts were washed with water, dried over
anhydrous sodium sulfate and evaporated. The crude product
was crystallized from acetonitrile to give 7 (3.45 g, 68% yield)
1
acetonitrile to give 11 (1.55 g, 74% yield), m.p.193-194°C; H
nmr: ꢀ 3.77 (s, 3H, CH3), 7.58 (d, 1H, J = 2.6 Hz, H-6'), 7.87 (d,
1H, J = 2.6 Hz, H-4'), 13.86 (br s, 1H, exchangeable with D2O,
NH); ir: ꢁ 3202 (NH), 1626 (CO) cm-1. Anal. Calc. (Found) for
C12H6BrCl4NO2: C, 34.49% (34.76%); H, 1.45% (1.58%); N,
3.35% (3.21%).
4-Bromo-3',5'-dichloro-2-(2'-methoxybenzoyl)pyrrole (12).
To a stirred solution of 6 (2.70 g, 10.0 mmoles) in acetonitrile
(100 ml), a solution of NBS (1.96 g, 11.0 mmoles, in 30 ml of
acetonitrile) was added drop by drop.
1
as white needles, m.p. 209-210°C; H nmr: ꢀ 3.70 (s, 3H, CH3),
7.53 (d, 1H, J = 2.5 Hz, H-6'), 7.64 (d, 1H, J = 2.5 Hz, H-4'),
13.70 (br s, 1H, exchangeable with D2O, NH); ir: ꢁ 3204 (NH),
1625 (CO) cm-1. Anal. Calc. (Found) for C12H6Br3Cl2NO2: C,
28.44% (28.65%); H, 1.19% 1.27%); N, 2.76% (2.64%).
After 6 hours the solvent was evaporated and the residue,
obtained as previously described for the preparation of 8, was
purified by column chromatography, using cyclohexane/ethyl
acetate 85/15 (v/v) as eluent. 12 was obtained as white crystals
1
4,3',5'-Trichloro-2-(2'-methoxybenzoyl)pyrrole (8). To a
solution of 2.70 g (10.0 mmoles) of 6 in 50 ml of acetonitrile,
1.50 g (11.0 mmoles) of solid NCS were added under stirring.
After 24 hours the mixture was evaporated. The residue was
suspended in 100 ml of water then extracted with diethyl ether
(3 x 50 ml). The combined extracts, dried over anhydrous
sodium sulfate, were evaporated and the residue was purified by
column chromatography, using 85/15 (v/v) cyclohexane/ethyl
acetate as eluent. 1.85g of 8 were obtained (yield 61%) as white
from ethanol, m.p. 120-121°C (2.48 g, 71% yield); H nmr: ꢀ
3.72 (s, 3H, CH3), 6.69 (s, 1H, H-3), 7.43 (s, 1H, H-5), 7.49 (d,
1H, J = 2.5 Hz, H-6'), 7.81 (d, 1H, J = 2.5 Hz, H-4'), 12.58 (br s,
1H, exchangeable with D2O, NH); ir: ꢁ 3250 (NH), 1630 (CO)
cm-1. Anal. Calc. (Found) for C12H8BrCl2NO2: C, 41.30%
(41.61%); H, 2.31% (2.48%); N, 4.01% (4.34%).
4-Bromo-5,3',5'-trichloro-2-(2'-methoxybenzoyl)pyrrole
(13). This compound was synthesized from 12 (1.75 g, 5.0
mmoles) and NCS (0.68 g, 50.0 mmoles) in 2.5 ml of
acetonitrile with the same procedure just described for the
preparation of 8. The crude product was chromatographed using
cyclohexane/ethyl acetate 90/10 (v/v) as eluent. 1.55 g of white
crystals, m.p.162-163°C from ethanol (81% yield) were
obtained; 1H nmr: ꢀ 3.72 (s, 3H, CH3), 6.81 (s, 1H, H-3), 7.51 (d,
1H, J = 2.5 Hz, H-6'), 7.82 (d, 1H, J = 2.5 Hz, H-4'), 13.57 (br s,
1H, exchangeable with D2O, NH); ir: ꢁ 3188 (NH), 1616 (CO)
cm-1. Anal. Calc. (Found) for C12H7BrCl3NO2: C, 37.59%
(37.68%); H, 1.84% (1.87%); N, 3.65% (3.57%).
1
crystals from ethanol, m.p.115-116°C; H nmr: ꢀ 3.74 (s, 3H,
CH3), 6.64 (d, 1H, J = 1.5 Hz, H-3), 7.42 (d, 1H, J = 1.5 Hz, H-
5), 7.50 (d, 1H, J = 2.5 Hz, H-6'), 7.82 (d, 1H, J = 2.5 Hz, H-4'),
12.54 (br s, 1H, exchangeable with D2O, NH); ir: ꢁ 3253 (NH),
1629 (CO) cm-1. Anal. Calc. (Found) for C12H8Cl3NO2: C,
47.32% (47.49%); H, 2.65% (2.73%); N, 4.60% (4.70%).
3,5-Dibromo-4,3',5'-trichloro-2-(2'-methoxybenzoyl)pyrrole
(10). To a solution of 8 (1.52 g, 5.0 mmoles) in 50 ml of
acetonitrile, a solution of NBS (1.78 g, 10.0 mmoles) in 50 ml of
acetonitrile was added drop by drop under stirring. After 12
hours, the reaction mixture was evaporated and the residue was
purified as previously described for the preparation of 8. The
crude product was crystallized from ethanol to give 10 (1.88 g,
3,4-Dibromo-5,3',5'-trichloro-2-(2'-methoxybenzoyl)pyrrole
(14). A solution of 13 (1.15 g, 30.0 mmoles) and NBS (0.54 g,
30 mmoles) was allowed to stand at room temperature. After 12
hours, the reaction mixture was evaporated and the residue was

Nov-Dec 2007
Synthesis and Anti-Staphylococcal Activity of New Halogenated Pyrroles
Related to Pyrrolomycins F
1411
purified as described previously for the preparation of 7.
Compound 14 was obtained as white crystals from acetonitrile,
m.p.200-201°C (1.0 g, 73% yield). 1H nmr: ꢀ 3.70 (s, 3H, CH3),
7.52 (d, 1H, J = 2.6 Hz, H-6'), 7.62 (d, 1H, J = 2.6 Hz, H-4'),
13.62 (br s, 1H, exchangeable with D2O, NH); ir: ꢁ 3192 (NH),
1626 (CO) cm-1. Anal. Calc. (Found) for C12H6Br2Cl3NO2: C,
31.17% (31.32%); H, 1.31% (1.40%); N, 3.03% (2.97%).
3-Bromo-4,5,3',5'-tetrachloro-2-(2'-hydroxybenzoyl)pyrrole
(5). This compound was obtained as yellow needles, mp 168-
169°C; 1H nmr: ꢀ 7.37 (d, 1H, J = 2.5 Hz, H-6'), 7.69 (d, 1H, J =
2.5 Hz, H-4'), 10.32 (br s, 1H, exchangeable with D2O, OH),
13.73 (br s, 1H, exchangeable with D2O, NH); ir: ꢁ 3272 (NH),
1578 (CO) cm-1. Anal. Calc. (Found) for C11H4BrCl4NO2: C,
32.71% (32.60%); H, 1.00% (0.95%); N, 3.47% (3.32%).
General procedure for the demethylation of O-methyl
derivatives. In a typical experiment, to a stirred suspension of
30 mmoles of aluminum chloride in 20 ml of dichloromethane in
ice bath, were added 3.0 mmoles of O-methyl derivative in 20
ml of the same solvent. The reaction mixture was stirred for 12
hours at room temperature, decomposed with a solution of ice /
5% sulfuric acid, then extracted with diethyl ether (2 x 100 ml).
The combined extracts were dried over anhydrous sodium
sulfate and evaporated. The crude compounds, obtained in
almost quantitative yields, were crystallized from ethanol.
Acknowledgements. Financial support from Fondi di Ateneo
Università degli Studi di Palermo, Italy, is gratefully
acknowledged.
REFERENCES AND NOTES
[1] Götz, F. Mol. Microbiol. 2002, 43, 1367.
[2] Koyama, M.; Ezaki, N.; Tsuruoka, T.; Inouye, S. J.
Antibiotics 1983, 36, 1483.
3,4,5-Tribromo-3',5'-dichloro-2-(2'-hydroxybenzoyl)pyrrole
(2). This compound was obtained as yellow needles, mp 204-
205°C; 1H nmr: ꢀ 7.35 (d, 1H, J = 2.4 Hz, H-6'), 7.68 (d, 1H, J =
2.4 Hz, H-4'), 10.25 (br s, 1H, exchangeable with D2O, OH),
13.60 (br s, 1H, exchangeable with D2O, NH); ir: ꢁ 3263 (NH),
1571 (CO) cm-1. Anal. Calc. (Found) for C11H4Br3Cl2NO2: C,
26.81% (26.87%); H, 0.82% (0.84%); N, 2.84% (2.68%).
3,5-Dibromo-4,3',5'-trichloro-2-(2'-hydroxybenzoyl)pyrrole
(3). This compound was obtained as yellow needles, mp 200-
201°C; 1H nmr: ꢀ 7.35 (d, 1H, J = 2.4 Hz, H-6'), 7.68 (d, 1H, J =
2.4 Hz, H-4'), 10.27 (br s, 1H, exchangeable with D2O, OH),
13.60 (br s, 1H, exchangeable with D2O, NH); ir: ꢁ 3266 (NH),
1570 (CO) cm-1. Anal. Calc. (Found) for C11H4Br2Cl3NO2: C,
29.47% (29.59%); H, 0.90% (0.96%); N, 3.12% (3.04%).
3,4-Dibromo-5,3',5'-trichloro-2-(2'-hydroxybenzoyl)pyrrole
(4). This compound was obtained as yellow needles, mp 209-
211°C; 1H nmr: ꢀ 7.36 (d, 1H, J = 2.5 Hz, H-6'), 7.69 (d, 1H, J =
2.5 Hz, H-4'), 10.25 (br s, 1H, exchangeable with D2O, OH),
13.72 (br s, 1H, exchangeable with D2O, NH); ir: ꢁ 3270 (NH),
1611 (CO) cm-1. Anal. Calc. (Found) for C11H4Br2Cl3NO2: C,
29.47% (29.64%); H, 0.90% (0.95%); N, 3.12% (2.99%).
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