Reduction of 2- and 3-acylpyrroles. A new synthesis of the pyrrolo[1,2-b]cinnolin-10-one ring system from 1-(4-methylphenyl)sulfonyl-1H-pyrrole

Article abstract of DOI:10.1016/S0040-4020(00)00922-4

Reduction of (2-nitrophenyl)(1H-pyrrol-2-yl)methanone 4 with zinc and ammonium chloride gave 5,10-dihydro-pyrrolo[1,2-b]cinnolin-10-one 5 and (2-hydroxylaminophenyl)(1H-pyrrol-2-yl)methanone 6 whereas reduction of 4 with zinc and sodium hydroxide gave only 5. Reaction of (2-nitrophenyl)(1H-pyrrol-3-yl)methanone 10 with zinc and ammonium chloride or zinc and sodium hydroxide afforded (2-nitrosophenyl)(1H-pyrrol-3-yl)methanone 11 and 2-aminophenyl)(1H-pyrrol-3-yl)methanone 12 or 12 as a single product, respectively. Sodium borohydride reduction of (2-nitrophenyl)(1-methyl-1H-pyrrol-2-yl)methanone 13 or (2-nitrophenyl)(1-methyl-1H-3-pyrrolyl)methanone 19 gave a mixture of the corresponding alcohols 15 or 21 and nitroso-ketones 18 or 22. Reduction of alcohols 15 or 21 with zinc and sodium hydroxide afforded nitroso-ketones 18 or 22, respectively. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4020(00)00922-4

TETRAHEDRON
Pergamon
Tetrahedron 56 (2000) 9675±9682
Reduction of 2- and 3-Acylpyrroles. A New Synthesis of the
Pyrrolo[1,2-b]cinnolin-10-one Ring System from
1-(4-Methylphenyl)sulfonyl-1H-pyrrole
*
Athanasios Kimbaris and George Varvounis
Department of Chemistry, University of Ioannina, 451 10, Ioannina, Greece
Received 7 July 2000; revised 13 September 2000; accepted 28 September 2000
AbstractÐReduction of (2-nitrophenyl)(1H-pyrrol-2-yl)methanone 4 with zinc and ammonium chloride gave 5,10-dihydro-pyrrolo[1,2-
b]cinnolin-10-one 5 and (2-hydroxylaminophenyl)(1H-pyrrol-2-yl)methanone 6 whereas reduction of 4 with zinc and sodium hydroxide
gave only 5. Reaction of (2-nitrophenyl)(1H-pyrrol-3-yl)methanone 10 with zinc and ammonium chloride or zinc and sodium hydroxide
afforded (2-nitrosophenyl)(1H-pyrrol-3-yl)methanone 11 and 2-aminophenyl)(1H-pyrrol-3-yl)methanone 12 or 12 as a single product,
respectively. Sodium borohydride reduction of (2-nitrophenyl)(1-methyl-1H-pyrrol-2-yl)methanone 13 or (2-nitrophenyl)(1-methyl-1H-3-
pyrrolyl)methanone 19 gave a mixture of the corresponding alcohols 15 or 21 and nitroso-ketones 18 or 22. Reduction of alcohols 15 or 21
with zinc and sodium hydroxide afforded nitroso-ketones 18 or 22, respectively. q 2000 Elsevier Science Ltd. All rights reserved.
Reactions involving the intramolecular capture of electro-
philic nitrene or nitroso species by an adjacent aromatic or
heteroaromatic ring have been exploited in the synthesis of
fused heteroaromatic systems, the reactions require reduc-
tion of appropriate aromatic nitro compounds. Cadogan
et al.1 were the ®rst to introduce triethyl phosphite for the
reduction of for example 2-nitrobiaryls into carbazoles, 1-o-
nitrophenylnaphthalene into 3,4-benzocarbazole, o-nitro-
anils into indazoles and 2-nitroazobenzenes into benzo-
triazoles. Similar conditions were used by Klemm et al.2
to transform 1-nitrotriphenylene into 4H-naphthol[1,4-
def]carbazole. These cyclisations require heating with neat
triethyl phosphite or in a solvent such as toluene and are
believed to proceed via nitrene intermediates, pyrroles
polymerise easily under these conditions. The only success-
ful cyclisation involving a pyrrole was the conversion of
1-(2-nitrophenyl)-1H-pyrrole into 9H-benzo[d]pyrrolo[1,2-
a]imidazole, reported by Lindley et al.3 An alternative
reductive process from nitro compounds involves intra-
molecular trapping of in situ generated nitroso species.
The reductive procedures employed here are milder
compared to those of triethyl phosphite. For example, zinc
dust and sodium hydroxide in re¯uxing aqueous ethanol has
been used by Bruneau et al.4 to cyclise N1-(alkyl or aryl)-2-
nitrobenzamides into 2-(alkyl or aryl)-2,3-dihydro-1H-3-
indazolones. Even milder conditions, zinc dust and ammo-
nium chloride in water and an organic solvent at ambient
temperature, were used by Bird and Latif5 for the cyclisation
of substituted 3-(2-nitrophenoxy)phenols into 3H-phenoxa-
zin-3-ones and by Mann and co-workers6 for the cyclisation
of ethyl 2-nitrophenylacetate into 4-hydroxy-1,4-benzoxa-
zine-3(4H)-one.
Here we report our ®ndings on the reduction of compounds
4, 13, 15, 19 and 21 with zinc dust in the presence of either
weak or relatively strong base. The starting materials 2 and
3 were not reported in the literature but were conveniently
prepared using the methods described by Kakushima et al.7
Thus 1-tosyl-1H-pyrrole 18 was acylated by o-nitrobenzoyl
chloride in 1,2-dichloroethane using either stannic chloride
or aluminium trichloride as catalyst. With stannic chloride
compounds 2 and 3 were isolated by column chromato-
graphy in 56 and 11% yield, respectively. The use of
aluminium trichloride gave, after column chromatography,
compounds 2 and 3 in 13 and 52% yield, respectively.
Kakushima et al.7 obtained better overall regioselectivity
synthesising
a range of 2-acyl-1-phenylsulfonyl-1H-
pyrroles from 1-phenylsulfonyl-1H-pyrrole with boron
tri¯uoride etherate as catalyst. No identi®able product
could be obtained when we used boron tri¯uoride etherate.
A similar observation was reported9 during attempted
Friedel±Crafts acylation of 1-(phenylsulfonyl)pyrrole with
2-(ethylthio)benzoyl chloride.
The substitution pattern in acyl pyrroles 2 and 3 was
determined by the use of pyrrole coupling constants and
chemical shifts.10 The most important distinction between
the two isomers is on one hand, H-5 is the most down®eld
pyrrole proton at dˆ7.91 ppm of compound 2 and in the
Keywords: pyrroles; reduction.
* Corresponding author. Tel.: 130-651-98-382; fax: 130-651-919-66;
e-mail: gvarvoun@cc.uoi.gr
0040±4020/00/$ - see front matter q 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(00)00922-4

9676
A. Kimbaris, G. Varvounis / Tetrahedron 56 (2000) 9675±9682
Scheme 1. Reagents: (a) 2-NO2C6H4COCl, ClCH2CH2Cl, catalyst, 228C.
other J2,5ˆ2.5 Hz of compound 3. Both these values are
comparable with the corresponding values dˆ7.80±7.91
and J2,5ˆ2.1±2.3 Hz found in a range of 2- and 3-acyl(1-
phenylsulfonyl or tosyl)pyrroles (Scheme 1).7,11
Reduction of 4 with zinc dust and ammonium chloride in
aqueous ethanol from 08C to room temperature, gave a
mixture consisting of pyrrolo[1,2-b]cinnolin-10-one 5
(45%) and hydroxylamine 6 (29%) (Scheme 2). Hamer et
al.12 reported the preparation of 5 by intramolecular
aromatic ¯uoride displacement in 2-(2-¯uorobenzoyl)-1H-
pyrrol-1-ylcarbamic acid ethyl ester. Re¯uxing 4 in aqueous
ethanol containing zinc dust and sodium hydroxide gave 5
in 68% yield. A plausible mechanism for the reductive
cyclisation of 4 into 5 is deoxygenation and deprotonation
to nitroso intermediate 7, intramolecular cyclisation to
N-oxide 8, protonation to N-hydroxy compound 9 and
reduction to 5. In the reaction of 4 with zinc and ammonium
chloride the formation of hydroxylamine 6 together with 5 is
probably due to the relatively weak basic conditions of the
redox reaction. The concentration of ammonia released
may be insuf®cient to produce stoichiometrically
deprotonated intermediate 7, so that further reduction of
protonated 7 leads to 6. No trace of the isomeric
pyrrolo[3,2-b]quinoline-9-one was observed in any of
these reactions.
Encouraged by the reported reductive cyclisation of 1-(2-
nitrophenyl)-1H-pyrrole with triethyl phosphite3 we decided
to try similar reaction conditions on compounds 2 and 3,
assuming that the -I/-M effects of the carbonyl and tosyl
groups in these compounds will tune down the reactivity
of the pyrrole rings. However, when compounds 2 and 3
were heated in neat triethyl phosphite, black tars were
produced, and when heated in toluene containing two
equivalents of triethyl phosphite, TLC examination of the
black mass revealed a faint spot that corresponded to start-
ing material. Failing to apply this method we turned to the
alternative reductive cyclisation based on intramolecular
capture of in situ generated aromatic nitroso compounds.
For this purpose we required methanones 4 and 10 since
the deprotected pyrrole rings of these compounds are
more nucleophilic in character than the pyrrole rings of 2
and 3. The latter were detosylated by re¯uxing in methanol
containing 2N aqueous sodium hydroxide to give 4 and 10
in 94 and 87% yield, respectively. Compound 4, was ®rst
reported by Khan and Morgan,12 and was prepared by the
action of pyrrolylmagnesium iodide on 2-nitrobenzoyl
chloride.
Contrary to the previous result, treating 10 with the zinc and
ammonium chloride gave a mixture of nitroso compound 11
(43%) and amine 12 (35%) (Scheme 3). Since nitroso
compounds are unstable under these conditions we assume
that the isolation of 11 results because of depletion of
Scheme 2. Reagents: (a) MeOH, NaOH, re¯ux; (b) Zn, NH4Cl, H2O, EtOH, 0±228C; (c) Zn, NaOH, H2O, EtOH, re¯ux.

A. Kimbaris, G. Varvounis / Tetrahedron 56 (2000) 9675±9682
9677
Scheme 3. Reagents: (a) MeOH, KOH, re¯ux; (b) Zn, NH4Cl, H2O, EtOH, 25±228C; (c) Zn, NaOH, H2O, EtOH, re¯ux.
reducing agent from reduction of 11 to 12. Treating 10 with
zinc and sodium hydroxide afforded the amine 12 in 71%
yield. Contrary to our expectations, no trace of the isomeric
compounds pyrrolo[2,3-b]quinolin-4-one and pyrrolo-
[3,4-b]quinoline-9-one were detected in these reactions.
(Schemes 4 and 5), an alternative route instead of the
obvious methylation of compounds 4 and 10 was investi-
gated. Friedel±Crafts acylation of 1-methylpyrrole with
2-nitrobenzoyl chloride in the presence of stannic chloride
was chosen by analogy to the synthesis of compounds 2 and
3. This route was abandoned since only 10% of compound
13 was isolated and a trace of compound 19 detected. On
the other hand, methylation of compounds 4 and 10 by
dissolving in dimethyl sulfoxide containing potassium
hydroxide and then treating with methyl iodide gave 13
and 19 in 76 and 80% yield, respectively. No trace of
C-alkylation was observed. Our initial thought was that
the 1I effect of the methyl group of compounds 13 and
19 would slightly increase the nucleophilic character of
the pyrrole ring and possibly facilitate cyclisation.
However, reduction of 13 and 19 with zinc and ammonium
chloride or zinc and sodium hydroxide afforded the amines
14 and 20, respectively. No trace of the anticipated 4,9-
dihydro-1H-1-methylpyrrolo[3,2-b]quinolin-9-one and 4,9-
dihydro-1H-1-methylpyrrolo[2,3-b]quinolin-9-one was de-
tected in these reactions.
An attempt to cyclise 11, by heating in p-xylene for 6 h
resulted in the recovery of starting material. Bates and
Tafel9 used similar reaction conditions to cyclise 3-
[2-(ethylsul®nyl)benzoyl]pyrrole into 1,2-dihydro-thio-
chromeno[2,3-b]pyrrol-4-one. It is therefore highly unlikely
that restricted rotation about the phenyl-acyl and pyrrole-
acyl bonds of 11 is responsible for locking the molecule into
a conformation where pyrrole ring and nitroso group are too
far apart for reaction. A plausible explanation is, on one
hand, that C-2 and C-4 of 11 are considerably less nucleo-
philic than N-1, and in the other, that the nitroso group of 11
is less electrophilic than the sulfoxide group of 3-[2-(ethyl-
sul®nyl)benzoyl]pyrrole.
In order to synthesise N-methylated derivatives 13 and 19
Scheme 4. Reagents: (a) KOH, DMSO, MeI; (b) Zn, NH4Cl, H2O, EtOH, 0±228C; (c) Zn, NaOH, H2O, EtOH, re¯ux; (d) NaBH4, IPA, re¯ux.

9678
A. Kimbaris, G. Varvounis / Tetrahedron 56 (2000) 9675±9682
Scheme 5. Reagents: (a) KOH, DMSO, MeI; (b) Zn, NH4Cl, H2O, EtOH, 0±228C; (c) Zn, NaOH, H2O, EtOH, re¯ux; (d) NaBH4, IPA, re¯ux.
Next we considered that alcohols 15 and 21 are good candi-
dates for reductive cyclisation since the 2I/2M effects
exercised by the carbonyl group in ketones 13 and 19
(Schemes 4 and 5) are absent in these compounds. The
pyrrole rings of 15 and 21 should therefore be more nucleo-
philic than the corresponding pyrrole rings of compounds 13
and 19. A literature search revealed that there are very few
reports on the reduction of acyl pyrroles to alcohols. Salvadori
and co-workers13 reduced 3-acetyl-1-tosyl-1H-pyrrole with
sodium borohydride and propan-2-ol in boiling dioxane and
obtained 3-(1-hydroxyethyl)-1-tosyl-1H-pyrrole in 70%
yield together with 3-ethyl-1-tosylpyrrole in 20% yield.
More recently, Xiao and Ketcha14 reported that reduction
of 3-acetyl-1-(phenylsulfonyl)-1H-pyrrole by sodium boro-
hydride in ethanol gave near quantitative yield of 3-(1-
hydroxyethyl)-1-(phenylsulfonyl)-1H-pyrrole. The reduc-
tion of compounds 13 and 19 required heating under re¯ux
in propan-2-ol with 1.5 equiv. of sodium borohydride and
gave a mixture consisting of nitro-alcohol and nitroso-
ketone, 15 and 21 and 18 and 22 (Schemes 4 and 5),
respectively. The compounds in these mixtures were easily
separated by column chromatography. We suggest that the
initial step in these reactions is straightforward reduction of
ketone to alcohol. In the presence of excess base the alcohol,
for example compound 15, tautomerises to the aci-nitro
intermediate 16 (Scheme 4). The latter rearranges to the
intermediate benzisoxazole 17 from which a molecule of
water is lost to afford nitroso compound 18. To our
knowledge, this transformation is unprecedented in the
literature. The closest analogy is the reaction of 2-nitro-
benzehydrol with p-toluenesulfonyl chloride to give 2-nitro-
sobenzophenone15 where an analogous benzisoxazole
intermediate was proposed. Further con®rmation of our
reaction path is provided by the quantitative conversion of
nitro-alcohols 15 and 21 into the corresponding nitroso-
ketones 18 and 22 by heating in propan-2-ol with excess
sodium borohydride.
In an attempt to produce tricycle 24 by treating nitro-alcohol
15 with zinc and sodium hydroxide, the reaction afforded
instead nitroso-ketone 18. Similar treatment of alcohol 21
afforded nitroso-ketone 22 (Scheme 6). We suggest that a
mechanism similar to the one depicted in Scheme 4 for the
conversion of 15 to 18 is taking place. The reason why
neither nitro group in 15 nor nitroso group in 18 are reduced
by the reductive reaction conditions is probably the rapid
Scheme 6. Reagents: (a) Zn, NaOH, H2O, EtOH, re¯ux.

A. Kimbaris, G. Varvounis / Tetrahedron 56 (2000) 9675±9682
9679
interconversion of 15 to aci-nitro intermediate 16 and the
slow conversion of the latter to intermediate benzoisoxazole
17. Both 16 and 17 are not reduced under these conditions
during which time the redox reaction between zinc and eth-
anol goes to completion. A similar explanation can be given
for the conversion of 21 to 22, where tricycles 25 and/or 26
were not formed. Nitroso compounds 18 and 22 were also
subjected to thermal activation in neutral or acidic condi-
tions, since it seemed to present a good possibility for intra-
molecular electrophilic aromatic substitution because the
high temperature would offer the greatest rotational free-
dom. Re¯uxing 18 or 22 in xylene, DMF or diglyme,
subliming at 658C/0.05 Torr or heating in PPA at 1008C
left the compounds unchanged. No products were
detected even when 18 or 22 were quenched in t-BuLi/
Et2O at 258C.
dark oil. Column chromatography of the oily residue (11%
ethyl acetate/light petroleum) gave two fractions. The ®rst
fraction gave {1-[(4-methylphenyl)sulfonyl]-1H-pyrrol-2-
yl}(2-nitrophenyl)methanone 2 and the second fraction
gave {1-[(4-methylphenyl)sulfonyl]-1H-pyrrol-3-yl}(2-nitro-
phenyl)methanone 3.
{1-[(4-Methylphenyl)sulfonyl]-1H-pyrrol-2-yl}(2-nitro-
phenyl)methanone (2). (0.84 g, 56%) as colourless plates
(toluene), mp 151±1528C (photosensitive); [Found: C,
58.35; H, 3.77; N, 7.55. C18H14N2O5S requires C, 58.37;
H, 3.81; N, 7.57%]; nmax (Nujol) 1660, 1520, 1340, 1320,
1160 cm21; dH (360 MHz; CDCl3) 2.43 (3H, s, Me), 6.28
(1H, t, Jˆ3.8 Hz, H-4), 6.46 (1H, dd, Jˆ3.8, 1.8 Hz, H-3),
7.35 (2H, d, Jˆ8.4 Hz, H-300, H-500), 7.47 (1H, dd, Jˆ7.5,
1.5 Hz, H-60), 7.61 (1H, td, Jˆ8.1, 1.5 Hz, H-40), 7.69 (1H,
td, Jˆ7.5, 1.2 Hz, H-50), 7.91 (1H, dd, Jˆ3.8 Hz, H-5), 7.97
(2H, d, Jˆ8.4 Hz, H-200, H-600), 8.01 (1H, dd, Jˆ8.1, 1.2 Hz,
H-30); dC (90.5 MHz; CDCl3) 21.7 (Me), 110.6 (C-4), 124.4
(C-3), 126.8 (C-40), 128.6 (C-300, C-500), 129.4 (C-50), 129.5
(C-200, C-600), 130.8 (C-60), 131.4 (C-5), 131.9 (C-2), 133.7
(C-30), 135.1(C-10), 135.4 (C-20), 143.3 (C-400), 146.8
(C-100), 179.8 (CO); m/z (EI) 370 (44, M1), 340 (19), 155
(100), 134 (23), 91 (88%).
Further work is under way in order to exploit the intra-
molecular capture of in situ generated nitroso species as a
means of synthesising fused heteroaromatic systems.
Experimental
General methods
{1-[(4-Methylphenyl)sulfonyl]-1H-pyrrol-3-yl}(2-nitro-
phenyl)methanone (3). (0.16 g, 11%) as colorless micro-
crystals (toluene), mp 163±1658C; [Found: C, 58.41, H,
3.78, N, 7.54. C18H14N2O5S requires C, 58.37, H, 3.98, N,
7.57%]; nmax (Nujol) 1670, 1530, 1350, 1330, and
1180 cm21; dH (360 MHz; CDCl3) 2.43 (3H, s, Me), 6.70
(1H, dd, Jˆ3.4, 1.7 Hz, H-4), 7.15 (1H, dd, Jˆ3.4, 2.0 Hz,
H-5), 7.34 (2H, d, Jˆ8.5 Hz, H-300, H-500), 7.40 (1H, t,
Jˆ1.8 Hz, H-2), 7.49 (1H, dd, Jˆ7.4, 1.5 Hz, H-60), 7.67
(1H, td, Jˆ8.2, 1.5 Hz, H-40), 7.75 (2H, d, Jˆ8.5, H-200,
H-600), 7.76 (1H, td, Jˆ7.4, 1.2 Hz, H-50), 8.15 (1H, dd,
Jˆ8.2, 1.2 Hz, H-30); dC (90.5 MHz; CDCl3) 21.7 (Me)
112.8 (C-4) 122.1 (C-5), 124.6 (C-40), 125.9 (C-2), 127.3
(C-300, C-500), 128.1 (C-3), 128.7 (C-50), 130.5 (C-200, C-600),
130.8 (C-60), 134.0 (C-30), 134.7 (C-10), 136.0 (C-20), 146.3
(C-400), 146.8 (C-100), 187.3 (CO); m/z (EI) 370 (18, M1),
342 (17), 236 (13), 215 (12), 187 (23), 155 (76), 91 (100%).
Melting points were taken on a BuÈchi 510 apparatus and are
uncorrected. Infrared spectra were recorded on a Perkin±
Elmer 257 spectrometer solids were taken as Nujol mulls
and liquids as thin ®lms between sodium chloride discs.
Elemental analyses were performed on a Carlo Erba 1106
elemental analyser. Nuclear magnetic resonance spectra
were measured at 360 MHz on a BruÈker AM 360 spectro-
meter or at 400 MHz on a BruÈker AMX 400 spectrometer
using tetramethylsilane as internal standard. Mass spectra
were obtained with a JEOL JMS-AX 505W (high-
resolution) machine using EI.
Analytical TLC was carried out on Fluka silica gel 60 F254
.
Preparative ¯ash chromatography was carried out through-
out using Merck 9385 silica gel. Light petroleum refers to
the fraction with bp 40±608C. Solvents and reagents were
used as received from the manufacturers except for
dichloromethane, ethanol, ethyl acetate, methanol and
light petroleum, which were puri®ed according to recom-
mended procedures.17
Reaction of 1-(4-methylphenyl)sulfonyl-1H-pyrrole with
benzoyl chloride in the presence of aluminium
trichloride
Reaction of 1-(4-methylphenyl)sulfonyl-1H-pyrrole with
benzoyl chloride and stannic chloride
The procedure of Kakushima et al.7 was essentially used. To
a stirred suspension of anhydrous aluminium trichloride
(1 g, 75 mmol) in 1,2-dichloroethane (60 mL) at 2108C
and under argon, was added o-nitrobenzoyl chloride
(1.3 mL, 7 mmol) and the mixture was stirred for 10 min.
The procedure of Kakushima et al.7 was essentially used. To
a stirred solution of stannic chloride (0.7 mL, 6 mmol) in
anhydrous 1,2-dichloroethane (30 mL) at 2108C and under
argon, was added slowly freshly distilled o-nitrobenzoyl
chloride (0.72 mL, 5.6 mmol). The resulting mixture was
stirred for 10 min. A solution of 1-(4-methylphenyl)sulfonyl-
1H-pyrrole8 (0.9 g, 4.07 mmol) in anhydrous 1,2-dichloro-
ethane (20 mL) was added dropwise, and the mixture stirred
for 30 min at 2108C and at 258C for 90 min. The reaction
was poured onto ice water (100 mL) and the aqueous layer
extracted with chloroform (3£20 mL). The combined
organic layers were treated with saturated NaHCO3, washed
with brine, dried (Na2SO4) and evaporated in vacuo to give a
A
solution of 1-(4-methylphenyl)sulfonyl-1H-pyrrole8
(1.12 g, 5.09 mmol) in anhydrous 1,2-dichloroethane
(30 mL) was added dropwise, and the temperature allowed
to reach 258C while stirring was continued. The reaction
mixture was poured onto ice water (130 mL), and the
aqueous layer extracted with chloroform (3£30 mL). The
combined organic layers were treated with saturated
NaHCO3, washed with brine, dried (Na2SO4), and evapo-
rated under reduced pressure to give a dark oil. The oily
residue was subjected to column chromatography (11%
ethyl acetate/light petroleum) to give two fractions. The

9680
A. Kimbaris, G. Varvounis / Tetrahedron 56 (2000) 9675±9682
®rst fraction gave {1-[(4-methylphenyl)sulfonyl]-1H-pyrrol-
3-yl}(2-nitrophenyl)methanone 3 (0.96 g, 52%). The second
fraction gave {1-[(4-methylphenyl)sulfonyl]-1H-pyrrol-2-
yl}(2-nitrophenyl)methanone 2 (0.23 g, 13%). Compounds
2 and 3 obtained by this method were identical in all
respects with the corresponding compounds prepared in
the previous experiment.
1 mmol) in ethanol (10 mL) at 08C was added zinc dust
(0.20 g, 3 mmol) followed by a solution of ammonium
chloride (0.32 g, 6 mmol) in water (5 mL). The reaction
mixture was left to stir at room temperature for 1.5 h,
®ltered and the residue washed with hot ethanol (10 mL).
The solvents were concentrated in vacuo to near dryness,
water (30 mL) was added and extracted with dichloro-
methane (3£10 mL). The combined organic extracts were
dried (Na2SO4), concentrated in vacuo, and the oily residue
was puri®ed by column chromatography (25% ethyl acetate/
light petroleum) to give two fractions. The ®rst fraction gave
5,10-dihydropyrrolo[1,2-b]cinnolin-10-one 516 or (2-nitroso-
phenyl)(1H-pyrrol-3-yl)methanone 11 and the second
fraction gave (2-hydroxyl-aminophenyl)(1H-pyrrol-3-yl)-
methanone 6 or (2-aminophenyl)(1H-pyrrol-3-yl)-metha-
none 12, respectively.
General procedure for the detosylation of {1-[(4-methyl-
phenyl)sulfonyl]-1H-pyrrol-2-yl}(2-nitrophenyl)-methan-
one and {1-[(4-methylphenyl)sulfonyl]-1H-pyrrol-
3-yl}(2-nitrophenyl)methanone
To a solution of 2 or 3 (0.93 g, 2.5 mmol) in methanol
(50 mL) was added 2N aqueous sodium hydroxide solution
(2 mL) and the resulting mixture was stirred under re¯ux for
5 h. After cooling to room temperature the solvent was
evaporated in vacuo to near dryness, water (30 mL) was
added and the pH adjusted to 4±5 by dropwise addition of
2N aqueous hydrogen chloride solution. The suspension was
extracted with chloroform (3£10 mL) the combined
organic extracts washed with brine, dried (Na2SO4) and
concentrated to give a light brown residue of crude (2-nitro-
phenyl)(1H-pyrrol-2-yl)methanone 4 or (2-nitrophenyl)(1H-
pyrrol-3-yl)methanone 10.
5,10-Dihydropyrrolo[1,2-b]cinnolin-10-one (5). (0.08 g,
45%) as colourless needles (ethanol); mpˆ130±1318C
(lit.12 mp.3008C) [Found: C, 71.73; H, 4.38; N, 15.21.
C11H8N2O requires C, 71.70; H, 4.39; N, 15.22%]; nmax
(Nujol) 3230, 1640 cm21; dH (400 MHz; CDCl3) 6.41
(1H, dd, Jˆ3.5, 2.6 Hz, H-2), 6.93±6.97 (2H, m, H-1 and
H-8), 7.07 (1H, dd, Jˆ2.6, 1.2 Hz, H-3), 7.28 (1H, td,
Jˆ8.3, 2.5 Hz, H-7), 7.50 (1H, dd, Jˆ8.3, 1.7 Hz, H-6),
7.69 (1H, dd, Jˆ8.7, 2.5 Hz, H-9), 9.93 (1H, s, br, NH);
dC (100.6 MHz; CDCl3) 110.6 (C-2), 111 (C-1), 112.2
(C-5a), 114.4 (C-8), 120.6 (C-3), 120.8 (C-9a), 122.3
(C-7), 123.2 (C-6), 131.2 (C-9), 157.5 (C-10a), 158.8
(CO); m/z (EI) 184 (100, M1), 167 (3), 155 (45), 129
(36), 103 (11), 92 (14), 66 (9%).
(2-Nitrophenyl)(1H-pyrrol-2-yl)methanone (4). (0.51 g,
94%) as colourless needles (toluene); mpˆ138±1408C
[Found: C, 61.14; H, 3.71; N, 12.95. C11H8N2O3 requires
C, 61.10; H, 3.73; N, 12.96%]; nmax (Nujol) 3300, 1630,
1490, 1350 cm21; dH (360 MHz; CDCl3) 6.27 (1H, td,
Jˆ3.9, 2.4 Hz, H-4), 6.51 (1H, td, Jˆ3.9, 2.4, 1.3 Hz,
H-3), 7.21 (1H, td, Jˆ2.4, 1.3 Hz, H-5), 7.62 (1H, td,
Jˆ7.5, 1.6 Hz, H-40), 7.66 (1H, dd, Jˆ7.5, 1.6 Hz, H-60),
7.73 (1H, td, Jˆ8.0, 1.2 Hz, H-50), 8.14 (1H, dd, Jˆ8.0,
1.2 Hz, H-30), 10.24 (1H, s, br, NH); dC (90.5 MHz;
CDCl3) 111.4 (C-4), 119.9 (C-3), 124.6 (C-40), 127.0
(C-5), 129.5 (C-50), 130±6 (C-60), 130±8 (C-2), 133.4
(C-30), 135.2 (C-10), 130.6 (C-60), 130.8 (C-2), 133.4
(C-30), 135.2 (C-10), 147.5 (C-20), 182.1 (CO); m/z (EI)
216 (21, M1), 134 (49), 104 (64), 94 (25), 82 (100%).
(2-Hydroxylaminophenyl)(1H-pyrrol-2-yl)methanone
(6). (0.06 g, 29%) as pale-yellow microcrystals (toluene);
mpˆ146±1478C [Found: C, 65.35; H, 4.99; N, 13.85.
C11H10N2O2 requires C, 65.34; H, 4.98; N, 13.83%]; nmax
(Nujol) 3320, 3250, 1620 cm21; dH (400 MHz; DMSO-d6)
6.28 (1H, dd, Jˆ4.0, 2.4 Hz, H-4), 6.78 (1H, dd, Jˆ4.0,
1.2 Hz, H-3), 6.88 (1H, td, Jˆ8.0, 1.6 Hz, H-50), 7.11
(1H, s, H-5), 7.35±7.46 (2H, m, H-30, H-40), 7.81 (1H, d,
Jˆ7.6, Hz, H-60), 8.00 (1H, s, NHOH), 9.06 (1H, s, NHOH),
10.71 (1H, s, NH); m/z (EI) 202 (100, M1), 181 (85), 165
(18), 156 (41%).
(2-Nitrophenyl)(1H-pyrrol-3-yl)methanone (10). (0.47 g,
87%) as colourless needles (2-propanol) mp 148±1498C;
[Found: C, 61.18, H, 3.74; N, 12.92. C11H8N2O3 requires
C, 61.09; H, 3.73; N, 12.96%]; nmax (Nujol) 3380, 1640,
1520, 1340 cm21; dH (360 MHz; CDCl3) 6.61 (1H, td,
Jˆ3.0, 1.6 Hz, H-4), 6.81 (1H, td, Jˆ3.0, 2.1 Hz, H-5),
7.15 (1H, dd, Jˆ3.2, 1.6 Hz, H-2), 7.54 (1H, dd, Jˆ7.5,
1.5 Hz, H-60), 7.62 (1H, td, Jˆ8.2, 1.5 Hz, H-40), 7.72
(1H, td, Jˆ7.5, 1.2 Hz, H-50), 8.13 (1H, dd, Jˆ8.2,
1.2 Hz, H-30), 8.65 (1H, s, br, NH); dC (90.5 MHz;
CDCl3) 109.6 (C-4), 120.0 (C-5), 124.3 (C-30), 124.9
(C-2), 128.9 (C-50), 130.1 (C-60), 112.64 (C-3), 132.47
(C-10), 144.35 (C-20), 176.76 (CO); m/z (EI) 216 (41,
M1), 199 (22), 188 (19), 171 (18), 144 (10), 104 (26), 94
(100), 82 (50%).
(2-Nitrosophenyl)(1H-pyrrol-3-yl)methanone (11). (0.09 g,
43%) as pale-yellow microcrystals (toluene); mpˆ151±
1538C [Found: C, 66.02; H, 4.02; N, 13.97. C11H8N2O2
requires C, 65.99; H, 4.03; N, 13.99%]; nmax (Nujol)
3320, 1640 cm21; dH (400 MHz; DMSO) 6.80 (1H, dd,
Jˆ2.8, 1.5 Hz, H-4), 6.90±6.95 (2H, m, H-40, H-5), 6.26
(1H, dd, Jˆ8.0, 0.8 Hz, H-50), 7.48±7.52 (2H, m, H-2,
H-60), 7.73 (1H, dd, Jˆ7.8, 0.8 Hz, H-30), 10.56 (1H, s,
NH); m/z (EI) 200 (2, M1), 184 (100), 155 (82), 129 (85),
69 (80%).
(2-Aminophenyl)(1H-pyrrol-3-yl)methanone (12). (0.06 g,
35%) as off-yellow microcrystals (toluene); mpˆ120±
1218C [Found: C, 70.92; H, 5.42; N, 15.03%. C11H10N2O
requires C, 70.95; H, 5.41; N, 15.04 %]; nmax (Nujol) 3510,
3480, 3280, 1630 cm21; dH (400 MHz; DMSO-d6) 6.41
(2H, NH2), 6.46 (1H, dd, Jˆ3.9, 2.4 Hz, H-4), 6.55 (1H,
td, Jˆ8.0, 1.0 Hz, H-50), 6.76 (1H, d, Jˆ8.0 Hz, H-30),
6.86 (1H, dd, Jˆ4.5, 2.2 Hz, H-5), 7.20 (1H, dd, Jˆ8.0,
Reduction of (2-nitrophenyl)(1H-pyrrol-2-yl)methanone
and (2-nitrophenyl)(1H-pyrrol-3-yl)methanone with
zinc dust and ammonium chloride in aqueous ethanol
General procedure A. To a solution of 4 or 10 (0.22 g,

A. Kimbaris, G. Varvounis / Tetrahedron 56 (2000) 9675±9682
9681
1.5 Hz, H-40), 7.26 (1H, s, H-2), 7.61 (1H, dd, Jˆ8.0,
1.5 Hz, H-60), 11.46 (1H, s, NH); m/z (EI) 186 (100, M1),
169 (82), 158 (12), 94 (38), 66 (11%).
Reduction of (2-nitrophenyl)(1-methyl-1H-pyrrol-2-yl)-
methanone and (2-nitrophenyl)(1-methyl-1H-3-
pyrrolyl)methanone with zinc dust and ammonium
chloride in aqueous ethanol
Reduction of (2-nitrophenyl)(1H-pyrrol-2-yl)methanone
and (2-nitrophenyl)(1H-pyrrol-3-yl)methanone with
zinc dust and sodium hydroxide in aqueous ethanol
Compound 13 or 19 (0.23 g, 1 mmol) was dissolved in
ethanol (10 mL), the solution cooled to 08C and treated
with zinc dust (0.20 g, 3 mmol) and aqueous ammonium
chloride (0.32 g, 6 mmol) according to General procedure
A. The oily residue after work-up was puri®ed by column
chromatography (33% ethyl acetate/light petroleum) to give
(2-aminophenyl)(1-methyl-1H-pyrrol-2-yl)methanone 14 or
(2-aminophenyl)(1-methyl-1H-3-pyrrolyl)methanone 20.
General procedure B. To a stirred solution of 4 or 10
(0.22 g, 1.0 mmol) in ethanol (10 mL) was added a solution
of sodium hydroxide (0.16 g, 4.0 mmol) in water (5 mL)
and zinc dust (0.20 g, 3 mmol). The resulting mixture was
heated under re¯ux over a period of 3 h, ®ltered, washed
with hot ethanol and the ®ltrate evaporated to near dryness.
Water (30 mL) was added to the oily residue and then
extracted with dichloromethane (3£10 mL). The combined
organic extracts were dried (Na2SO4) and evaporated in
vacuo to give a residue either of 5,10-dihydropyrrolo[1,2-
b]cinnolin-10-one 5 (0.13 g, 68%) or 2-aminophenyl)(1H-
pyrrol-3-yl)methanone 12 (0.13 g, 71%). Compounds 5
and 12 prepared by this method were identical in all
respects to the corresponding compounds obtained by
General procedure A.
Reduction of (2-nitrophenyl)(1-methyl-1H-pyrrol-2-yl)-
methanone and (2-nitrophenyl)(1-methyl-1H-3-
pyrrolyl)methanone with zinc dust and sodium
hydroxide in aqueous ethanol
Compound 13 or 19 (0.23 g, 1 mmol) was dissolved in
ethanol (10 mL) and treated with a solution of sodium
hydroxide (0.16 g, 4.0 mmol) in water (5 mL) and zinc
dust (0.20 g, 3 mmol) according to General procedure B.
After work-up the residue obtained was puri®ed by column
chromatography (33% ethyl acetate/light petroleum) to give
(2-aminophenyl)(1-methyl-1H-pyrrol-2-yl)methanone 14
(0.15 g, 77%) or (2-aminophenyl)(1-methyl-1H-3-pyrrolyl)-
methanone 20 (0.14 g, 71%). Compounds 14 and 20
prepared by this method were identical in all respects to
the corresponding compounds obtained by General
procedure A.
General procedure for the methylation of (2-nitro-
phenyl)(1H-pyrrol-2-yl)methanone and (2-nitrophenyl)-
(1H-pyrrol-3-yl)methanone
To a stirred solution of potassium hydroxide (0.22 g,
4 mmol) in dry dimethyl sulfoxide (10 mL) under argon,
was added (2-nitrophenyl)(1H-pyrrol-2-yl)methanone or
(2-nitrophenyl)(1H-pyrrol-3-yl)methanone (0.22 g, 1 mmol)
and the resulting mixture was stirred at room temperature
for 1 h. The reaction mixture was cooled to 108C, methyl
iodide was added dropwise and stirring continued at room
temperature for 45 min. Water (50 mL) was added and
extracted with diethyl ether (3£15 mL). The combined
organic extracts were dried (Na2SO4) and evaporated to
give crude (2-nitrophenyl)(1-methyl-1H-pyrrol-2-yl)metha-
none 13 or (2-nitrophenyl)(1-methyl-1H-pyrrol-3-yl)metha-
none 19.
(2-Aminophenyl)(1-methyl-1H-pyrrol-2-yl)methanone
(14). (0.16 g, 81%) as pale-yellow microcrystals (toluene);
mpˆ123±1248C [Found C, 71.95; H, 6.02; N, 13.98.
C12H12N2O requires C, 71.98; H, 6.04; N, 13.99%]; nmax
(Nujol) 3480, 3370, 1635 cm21; dH (400 MHz; CDCl3)
3.99 (3H, s, Me), 5.47 (2H, s, NH2), 6.14 (1H, dd, Jˆ4.0,
2.5 Hz, H-4), 6.65±6.71 (3H, m, H-3, H-30, H-50), 6.87 (1H,
t, Jˆ2.5 Hz, H-5), 7.25 (1H, td, Jˆ8.2, 1.2 Hz, H-40), 7.69
(1H, dd, Jˆ7.9, 1.5 Hz, H-60); m/z (EI) 200 (100, M1), 183
(51), 172 (21), 119 (36), 81 (27%).
(2-Nitrophenyl)(1-methyl-1H-pyrrol-2-yl)methanone (13).
(0.17 g, 76%) as colourless microcrystals (toluene);
mpˆ72±748C [Found: C, 62.62; H, 4.36; N, 12.16.
C12H10N2O3 requires C, 62.60; H, 4.38; N, 12.17%]; nmax
(Nujol) 1640, 1540, 1360 cm21; dH (400 MHz; CDCl3) 4.09
(3H, s, Me), 6.07 (1H, dd, Jˆ4.0, 2.4 Hz, H-4), 6.32 (1H, dd,
Jˆ4.0, 1.6 Hz, H-3), 6.92 (1H, s, H-5), 7.56±7.70 (3H, m,
H-40, H-50, H-60), 8.12 (1H, d, H-30); m/z (EI) 230 (100,
M1), 214 (35), 169 (82), 158 (22), 131 (58%).
(2-Aminophenyl)(1-methyl-1H-3-pyrrolyl)methanone
(20). (0.15 g, 74%) as pale-yellow microcrystals (toluene);
mpˆ137±1388C [Found C, 71.96; 7H, 6.05; N, 13.95.
C12H12N2O requires C, 71.98; H, 6.04; N, 13.99%]; nmax
(Nujol) 3545, 3425, 1640 cm21; dH (400 MHz; CDCl3)
3.68 (3H, s, Me), 6.41 (2H, NH2), 6.46 (1H, dd, Jˆ3.9,
2.4 Hz, H-4), 6.55±6.67 (3H, m, H-30, H-5, H-50), 6.88
(1H, s, H-2), 7.21 (1H, dd, Jˆ8.3, 1.3 Hz, H-40), 7.63
(1H, dd, Jˆ7.8, 1.3 Hz, H-60); m/z (EI) 200 (M1, 100),
183 (71), 171 (41), 157 (36), 108 (17), 81 (31%).
(2-Nitrophenyl)(1-methyl-1H-3-pyrrolyl)methanone (19).
(0.18 g, 80%) as colourless microcrystals (toluene);
mpˆ109±1118C [Found C, 62.59; H, 4.37; N, 12.20.
C12H10N2O3 requires C, 62.60; H, 4.38; N, 12.17%]; nmax
(Nujol) 1640, 1530, 1360 cm21; dH (400 MHz; CDCl3) 3,64
(3H, s, Me), 6.51 (1H, dd, Jˆ2.8, 1.8 Hz, H-4), 6.59 (1H, dd,
Jˆ2.8, 2.4 Hz, H-5), 6.97 (1H, s, H-2), 7.52 (1H, dd, Jˆ7.5,
1.0 Hz, H-60), 7.60 (1H, td, Jˆ8.1, 1.0 Hz, H-40), 7.69 (1H,
td, Jˆ7.5, 1.2 Hz, H-50), 8.11 (1H, dd, Jˆ8.1, 1.2 Hz, H-30);
m/z (EI) 230 (M1, 100), 214 (26), 169 (78), 144 (12), 131
(38%).
Reduction of (2-nitrophenyl)(1-methyl-1H-pyrrol-2-yl)-
methanone and (2-nitrophenyl)(1-methyl-1H-3-
pyrrolyl)methanone with sodium borohydride in 2-
propanol
General procedure C. To a solution of 13 or 19 ((0.35 g,
1.5 mmol) in 2-propanol (25 mL) was added sodium boro-
hydride ((0.08 g, 2.1 mmol). The reaction suspension was
re¯uxed for 18 h, after which the solvent was evaporated to

9682
A. Kimbaris, G. Varvounis / Tetrahedron 56 (2000) 9675±9682
dryness, water (30 mL) was added to the residue, and
extracted with dichloromethane (3£10 mL). The combined
organic extracts were dried (Na2SO4) and evaporated to
give an oily yellow-brown residue which was puri®ed by
column chromatography (20% ethyl acetate/light petro-
leum) to give two fractions. The ®rst fraction gave (2-nitro-
phenyl)(1-methyl-1H-pyrrol-2-yl)methanol 15 or (2-
nitrophenyl)(1-methyl-1H-pyrrol-3-yl)methanol 21 and the
second fraction gave (2-nitrosophenyl)(1H-pyrrol-2-
yl)methanone 18 or (2-nitrosophenyl)(1H-pyrrol-3-yl)metha-
none 22, respectively.
(20 mL) and treated with a solution of sodium hydroxide
(0.07 g, 4.0 mmol) in water (5 mL) and zinc dust (0.06 g,
0.86 mmol) according to General procedure B. After work-
up the residue obtained was puri®ed by column chromato-
graphy (11% ethyl acetate/light petroleum) to give (1-methyl-
1H-pyrrol-2-yl)(2-nitrosophenyl)methanone 18 (0.06 g,
58%) or (1-methyl-1H-pyrrol-3-yl)(2-nitrosophenyl)methan-
one 22 (0.05 g, 52%). Compounds 18 and 22 prepared by this
method were identical in all respects to the corresponding
compounds obtained by the previous experiment.
(2-Nitrophenyl)(1-methyl-1H-pyrrol-2-yl)methanol (15).
(0.13 g, 42%) as a pale-yellow oil bpˆ134±1378C/12 Torr;
Acknowledgements
n
max(liquid ®lm) 3380, 1530, 1355 cm21; dH (400 MHz;
CDCl3) 2.29 (1H, s, br, OH), 3.75 (3H, s, Me), 5.53 (1H,
s, CHOH), 5.94 (1H, d, Jˆ2.8 Hz, H-5), 6.56±6.61 (2H, m,
H-3, H-5), 7.47 (1H, t, Jˆ6.0, 1.0 Hz, H-40), 7.68 (1H, t,
Jˆ6.5, Hz, H-50), 7.93±7.98 (2H, m, H-30, H-60); m/z (EI)
232 (25, M1), 200 (19), 169 (17), 150 (29), 96 (100), 81
(12%); HRMS (EI): M1, found 232.0831 C12H12N2O3
requires 232.0848.
This work was supported by a PENED grant from the
General Secretariat of Research and Technology, Athens.
We thank Dr A. Troganis for NMR spectra measured on a
BruÈker AMX 400 spectrometer ®nanced by the University
of Ioannina. We are particularly grateful to J. Cobb for
NMR spectra recorded on a BruÈker AM 360 spectrometer
and to A. Cakebread and R. Tye for mass spectra obtained
on a JEOL JMS-AX 505W, machines funded by the Univer-
sity of London Intercollegiate Research Services Scheme.
(1-Methyl-1H-pyrrol-2-yl)(2-nitrosophenyl)methanone
(18). (0.17 g, 48%) as pale-yellow microcrystals (diethyl
ether) mpˆ59±618C; nmax (Nujol) 1640 cm21
;
dH
(400 MHz; CDCl3) 4.02 (3H, s, Me), 6.31 (1H, dd, Jˆ3.8,
2.7 Hz, H-4), 6.86±6.88 (2H, m, H-3, H-5), 6.98 (1H, t,
Jˆ8.8, 1.0 Hz, H-40), 7.30 (1H, t, Jˆ9.1, 0.8 Hz, H-50),
7.53 (1H, dd, Jˆ9.1, 1.0 Hz, H-30), 7.68 (1H, dd, Jˆ8.8,
0.8 Hz, H-30); m/z (EI) 214 (11, M1), 197 (100), 183 (61),
169 (73), 155 (58), 69 (48%); HRMS (EI): M1, found
214.0745 C12H10N2O2 requires 214.0742.
References
1. Cadogan, J. I. G.; Cameron-Wood, M.; Mackie, R. M.; Searle,
R. J. G. J. Chem. Soc. 1965, 4831.
2. Klemm, L. H.; Norris, E. S. J. Heterocycl. Chem. 1995, 32, 797.
3. Lindley, J. L.; McRobbie, I. M.; Meth-Cohn, O.; Suschitzky,
H. J. Chem. Soc., Perkin Trans. 1 1977, 2194.
(2-Nitrophenyl)(1-methyl-1H-pyrrol-3-yl)methanol (21).
(0.17 g, 47%) as a pale-yellow oil bp 143±1458C/12 Torr;
n
4. Bruneau, P.; Delvare, C. J. Med. Chem. 1991, 34, 1028.
5. Bird, C. W.; Latif, M. Tetrahedron 1980, 36, 529.
max(liquid ®lm) 3525, 1555, 1360 cm21; dH (400 MHz;
È
6. Sicker, D.; Pratorius, B.; Mann, G.; Meyer, L. Synthesis 1989,
211.
CDCl3) 2.49 (1H, s, br, OH), 3.59 (3H, s, Me), 6.02 (1H,
t, Jˆ2.2 Hz, H-4), 6.41 (1H, s, CHOH), 6.49±6.52 (2H, m,
H-2, H-5), 7.44 (1H, td, Jˆ8.4, 1.4 Hz, H-40), 7.65 (1H, td,
Jˆ7.9, 1.2 Hz, H-50), 7.90 (1H, dd, Jˆ8.4, 1.4 Hz, H-60),
7.97 (1H, dd, Jˆ7.9, 1.2 Hz, H-30); m/z (EI) 232 (17, M1),
197 (51), 184 (60), 170 (89), 155 (69), 128 (42), 108 (98), 81
(100%); HRMS (EI): M1, found 233.0882 C12H12N2O3
requires 233.0881.
7. Kakushima, M.; Hamel, P.; Frenette, R.; Rokach, J. J. Org.
Chem. 1983, 48, 3214.
8. (a) Anderson, H. J.; Loader, C. E.; Xu, R. X.; Nghia L.; Gogan,
N. J.; McDonald, R.; Edwards, L. G. Can. J. Chem. 1985, 63, 896.
(b) Papadopoulos, E. P.; Haidar, N. F. Tetrahedron Lett. 1968, 14,
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9. Bates, D. K.; Tafel, K. A. J. Org. Chem. 1994, 53, 8076.
10. Palmer, M. H.; Leitch, D. S.; Greenhalgh, C. W. Tetrahedron
1978, 34, 1015.
(1-Methyl-1H-pyrrol-3-yl)(2-nitrosophenyl)methanone
(22). (0.08 g, 25%) as pale-yellow microcrystals (diethyl
ether) mpˆ49±508C; nmax (Nujol) 1650 cm21
;
dH
11. Khan, M. K. A.; Morgan, K. J. J. Chem. Soc. 1964, 2579.
12. Hamer, R. R. L.; Sekerak, D.; Ef¯and, R. C.; Klein, J. T.
J. Heterocycl. Chem. 1998, 25, 991.
(400 MHz; CDCl3) 3.77 (3H, s, Me), 6.73±6.76 (2H, m,
H-4, H-5), 6.93 (1H, td, Jˆ8.8, 1.0 Hz, H-40), 7.27 (1H,
td, Jˆ9.1, 0.9 Hz, H-50), 7.32 (1H, t, Jˆ1.8, Hz, H-2),
7.51 (1H, dd, Jˆ9.1, 4.0 Hz, H-60), 7.69 (1H, dd, Jˆ8.8,
0.9 Hz, H-30); m/z (EI) 214 (21, M1), 198 (100), 183 (78),
169 (82), 108 (71), 69 (79%). HRMS (EI): M1, found
214.0741 C12H10N2O2 requires 214.0742.
13. Settambolo, R.; Lazzaroni, R.; Messeri, T.; Mazzetti, M.;
Salvadori, P. J. Org. Chem. 1993, 58, 7899.
14. Xiao, D.; Ketcha, D. M. J. Heterocycl. Chem. 1995, 32, 499.
15. Dickinson, W. B. J. Am. Chem. Soc. 1964, 86, 3580.
16. Hamer et al.12 gave a mp.3008C for the same compound
prepared by a different method. The dH values they reported do
not coincide with the dH values of 5 in the same solvent.
17. Perrin, D. D.; Armarego, W. L. Puri®cation of Laboratory
Chemicals; Pergamon: Oxford, 1988.
Reduction of (2-nitrophenyl)(1-methyl-1H-pyrrol-2-yl)-
methanol and (2-nitrophenyl)(1-methyl-1H-pyrrol-3-yl)-
methanol with zinc dust and sodium hydroxide in
aqueous ethanol
Compound 15 or 21 (0.43 mmol) was dissolved in ethanol