Novel electrophilic ipso acylation - Detosylation reaction of pyrroles

Article abstract of DOI:10.1139/V06-075

A pyrrole and two pyrroloindoles that are substituted with a p-toluenesulfonyl group undergo an ipso acylation - detosylation reaction with acid chlorides and aluminum chloride to afford the corresponding acyl-substituted pyrroles and pyrroloindoles.

Full text of DOI:10.1139/V06-075

1338
Novel electrophilic ipso acylation – detosylation
reaction of pyrroles1
Erin T. Pelkey and Gordon W. Gribble
Abstract: A pyrrole and two pyrroloindoles that are substituted with a p-toluenesulfonyl group undergo an ipso
acylation – detosylation reaction with acid chlorides and aluminum chloride to afford the corresponding acyl-substituted
pyrroles and pyrroloindoles.
Key words: pyrrole, pyrroloindole, ipso acylation, detosylation, Friedel–Crafts reaction.
Résumé : Sous l’action de chlorures d’acides et de chlorure d’aluminium, un pyrrole et deux pyrroindoles substitués
par un groupe p-toluènesulfonyle subissent des réactions d’acétylation-détosylation ipso qui conduisent à la formation
des pyrroles et pyrroindoles correspondants substitués par un groupe acyle.
Mots clés : pyrrole, pyrroindole, acétylation ipso, détosylation, réaction de Friedel–Crafts.
[Traduit par la Rédaction] Pelkey and Gribble 1342
Introduction
sis (K2CO3, MeOH, reflux, 78%) of the known 2-acetyl-3-
ethyl-1-(phenylsulfonyl)pyrrole (14). Direct comparison of
these two pyrroles reveals that the product of the acetylation
of 4 was clearly 5 and not 8. We view this ipso acylation –
detosylation reaction as involving ipso electrophilic attack at
C-5 in 4 followed by chloride attack on the sulfonyl group to
give p-toluenesulfonyl chloride and pyrrole 5.
This ipso acylation – detosylation was extended to the
synthesis of acylated pyrroloindoles (Scheme 2). Thus, treat-
ment of pyrrolo[2,3-b]indole 10 and pyrrolo[3,4-b]indole 13
with acetyl chloride and valeryl chloride in the presence of
aluminum chloride affords the acylated analogues 11 and 14,
respectively. Pyrroloindoles 10 and 13 were synthesized with
TosMIC from indoles 9 and 12, respectively, according to
our earlier method (10).
Whereas electrophilic ipso substitution (1) of aromatic and
heteroaromatic compounds, including organosilanes (2),
organostannanes (3), and several other substrates (4), is well-
documented, there appear to be no examples of organo-
sulfones undergoing electrophilic ipso substitution. For example,
treatment of 3-phenyl-4-(p-toluenesulfonyl)furan with acetyl
chloride and AlCl3 gives only the expected electrophilic
product, 2-acetyl-3-phenyl-4-(p-toluenesulfonyl)furan (5).
On the other hand, free radical ipso stannylation – detosyl-
ation reactions of 1-(phenylsulfonyl)-2-(p-toluenesulfonyl)
indole and related heterocycles have been described (6).
Results and discussion
In summary, we have discovered a novel electrophilic ipso
acylation – detosylation reaction of α-tosylpyrroles. In the
context of van Leusen and Barton–Zard pyrrole syntheses,
the reagent TosMIC (3) can be viewed as a synthetic equiva-
lent for α-isocyanoketones (15). Compounds related to 15
have previously been generated from α-metalated oxazoles
(15), but they have not been employed in these pyrrole ring
syntheses.
In connection with our interest in the closely related
Barton–Zard (7), van Leusen (8), and Montforts (9) synthe-
ses of pyrroles (10), we had occasion to examine the
Friedel–Crafts acylation of 4-ethyl-2-(p-toluenesulfonyl)pyrrole
(4). This compound was readily prepared by treating either
2-nitrobutyl acetate (1) (11) or 2-nitro-1-butene (2) (12) with
TosMIC (3) (13) and DBU in the presence of isopropanol
Scheme 1). Treatment of 4 with acetyl chloride in the pres-
ence of aluminum chloride affords 2-acetyl-4-ethylpyrrole
(5) and not the expected 2-acetyl-3-ethyl-5-(p-toluene-
sulfonyl)pyrrole (6). The characteristic odor of p-toluene-
sulfonyl chloride (7) in the reaction mixture was indicative
of this novel transformation. To confirm the regiochemistry
of 5, we synthesized 2-acetyl-3-ethylpyrrole (8) by hydroly-
O
ϵ
C=NCH2SO2Tol
C=NCH2CR
3
15
Received 14 November 2005. Accepted 31 March 2006. Published on the NRC Research Press Web site at http://canjchem.nrc.ca
on 12 August 2006. Reposted on the Web site with correction on 25 August 2006.
Dedicated to Dr. Alfred Bader, organic chemistry pioneer and art connoisseur extraordinaire. Thank you for giving us decades of
wonderful service and for rejuvenating our appreciation of art.
E.T. Pelkey and G.W. Gribble.2 Department of Chemistry, Dartmouth College 6128 Burke Laboratory, Hanover, NH 03755, USA.
1This article is part of a Special Issue dedicated to Dr. Alfred Bader.
Can. J. Chem. 84: 1338–1342 (2006)
doi:10.1139/V06-075
© 2006 NRC Canada

Pelkey and Gribble
1339
Scheme 1.
Et
C=NCH2SO2Tol
C=NCH2SO2Tol
OAc
NO2
3
3
Et
NO2
Ts
Et
DBU
N
H
DBU
THF, i-PrOH
63%
THF, i-PrOH
1
4
2
55%
MeCOCl
AlCl3
64%
SO2Cl
Et
Et
Et
Me
Me
Me
Ts
N
N
N
H
H
H
O
O
O
Me
8
6
5
7
Scheme 2.
NO2
3
MeCOCl
AlCl3
Me
DBU
THF
N
N
H
N
N
N
H
SO2Tol
PhO2S
O
SO2Ph
PhO2S
48%
63%
9
11
10
O
NO2
3
Cl
NH
NH
DBU
THF
21%
AlCl3
67%
N
N
N
SO2Tol
i-BuO2C
13
i-BuO2C
CO2i-Bu
O
12
14
performed by Atlantic Microlabs, Inc. (Norcross, Georgia).
Tetrahydrofuran (THF) and diethyl ether (ether) were dis-
tilled from sodium-benzophenone ketyl. Diisopropylamine,
dichloromethane, xylenes, and triethylamine were distilled
from calcium hydride. Acetyl chloride, hexanoyl chloride,
trimethylsilyl chloride, and valeryl chloride were distilled
from 0.1% quinoline. Unless otherwise indicated, all other
reagents and solvents were purchased from commercial
sources and were used without further purification. All reac-
tions were performed under a positive nitrogen atmosphere
with magnetic stirring unless otherwise noted. All glassware
was oven-dried at >130 °C and allowed to cool in a desicca-
tor (Drierite®) before assembly under positive nitrogen.
Experimental
Melting points were determined using open capillary
tubes and are uncorrected. Thin-layer chromatography
(TLC) was performed on regular TLC plates. Visualization
of developed plates was achieved with a 254 nm UV lamp
and (or) with iodine. Flash chromatography utilized 230–
400 mesh silica gel 60. H NMR and 13C NMR were run at
1
300 and 75 MHz, respectively. Chemical shifts (δ) are re-
ported in ppm using the solvent residual proton or carbon
signal (CDCl3: H, 7.27, C, 77.23) as an internal reference.
The apparent multiplicity (singlet (s), doublet (d), triplet (t),
quartet (q), septet (sept), multiplet (m), broad (br)), number
of protons, and coupling constants (in Hz) are reported in
that order in parenthesis after the chemical shift. Infrared
spectra (IR) are reported in reciprocal centimeters and were
obtained using neat compounds (neat), solid KBr pellets (KBr),
polyethylene IR cards (PE), or polytetrafluoroethylene IR
cards (PTFE). High-resolution mass spectrometry (HRMS)
was performed at the University of Illinois (Urbana-
Champaign, Illinois) mass spectrometry laboratory or by the
SOCAL Mass Spectrometry Facility at the University of
California (Riverside, California). Elemental analyses were
2-Nitro-1-butanol
A modification of a literature procedure was utilized (11).
To a 0 °C stirred solution of sodium hydroxide (4.20 g,
105 mmol) dissolved in distilled water (40 mL) was added
1-nitropropane (8.91 g, 100 mmol) dropwise. The reaction
mixture was stirred at 0 °C for 30 min and then at room tem-
perature (rt) for 1 h. Upon recooling to 0 °C, the reaction
mixture was treated with an aqueous solution of formalin
© 2006 NRC Canada

1340
Can. J. Chem. Vol. 84, 2006
(37%, 8.52 g, 105 mmol) dropwise via addition funnel over
10 min and then the reaction mixture was stirred at rt for
7 h. Upon recooling to 0 °C, the reaction mixture was
treated with acetic acid (6.60 g, 110 mmol) dropwise and
stirred for 3 h. The aqueous solution was extracted with
ether (5 × 50 mL) and the combined organic extracts were
washed with brine (200 mL) and dried over sodium sulfate.
Removal of the solvent in vacuo gave a yellow oil (20 g)
that was purified by vacuum distillation through a Vigreux
column. The desired product was obtained as a colorless oil.
Yield: 6.57 g, 55.1 mmol, 55%; bp 124 to 125 °C at 10 Torr
(1 Torr = 133.322 4 Pa) (lit. value (11) bp 90–92 °C at 3
chromatography (hexanes; CH2Cl2–hexanes, 1:1; CH2Cl2–
hexanes, 3:1). After eluting a brightly colored yellow impu-
rity (Rf 0.38; CH2Cl2–hexanes, 3:1), the desired product 4
was obtained as a yellow amorphous solid. Yield: 372 mg,
1
80% pure by H NMR, 1.25 mmol, 63% yield based on
NMR integration. Recrystallization (CH2Cl2–hexanes, 1:4)
gave 4 as off-white needles; mp 94 to 95 °C. Rf 0.15
(CH2Cl2–hexanes, 3:1). IR (PTFE, cm–1) υmax: 3306 (NH),
2964, 2924, 2872, 1595, 1494, 1440, 1379, 1301, 1202,
1
1146. H NMR (CDCl3) δ: 8.90 (br s, 1H), 7.80–7.83 (m,
2H), 7.26 (m, 2H), 6.70–6.75 (m, 2 H), 2.45 (q, 2H, J =
7.5 Hz), 2.39 (s, 3H), 1.15 (t, 3H, J = 7.5 Hz). 13C NMR
(CDCl3) δ: 143.9, 139.9, 130.0, 129.0, 127.7, 127.0, 121.1,
114.8, 21.7, 20.0, 15.0. MS m/z (%): 250 (M+ + 1), 249
(M+), 234 (100%), 184, 170, 142, 127, 110, 91, 78, 65.
Anal. calcd. for C13H15NO2S: C 62.63, H 6.06, N 5.62, S
12.83; found: C 62.57, H 6.05, N 5.56, S 12.95.
1
Torr). H NMR (CDCl3) δ: 4.51–4.59 (m, 1H) 3.89–4.10 (m,
2H), 1.81–2.06 (m, 3H), 1.02 (t, J = 7.2 Hz, 3H). 13C NMR
(CDCl3) δ: 90.8, 63.1, 23.5, 10.4.
2-Nitrobutyl acetate (1)
A modification of the literature procedure for synthesizing
β-nitroacetates was utilized (16). To a 0 °C stirred solution
of 2-nitro-1-butanol (5.59 g, 47.0 mmol) dissolved in
CH2Cl2 (50 mL) was added acetic anhydride (5.72 g,
56.0 mmol) followed by p-toluenesulfonic acid monohydrate
(380 mg, 2.0 mmol). The reaction mixture was stirred at
0 °C and then at rt for 8 h. Removal of the solvent in vacuo
gave a residue (10 g) that was purified by vacuum distilla-
tion through a Vigreux column. The desired product 1 was
obtained as a light yellow oil. Yield: 6.57 g, 40.1 mmol,
86%; bp 88 to 89 °C at 4 Torr (lit. value (11) bp 70–72 °C at
2-Acetyl-4-ethylpyrrole (5)
To a 0 °C stirred suspension of aluminum chloride
(333 mg, 2.50 mmol) in CH2Cl2 (5 mL) was added freshly
distilled (from quinoline) acetyl chloride (79 mg, 1.00 mmol)
and the mixture was stirred for 15 min and then treated with
a
solution of 4-ethyl-2-(p-toluenesulfonyl)pyrrole (4)
(125 mg, 0.500 mmol) dissolved in CH2Cl2 (5 mL)
dropwise. The reaction mixture was stirred at 0 °C for 1 h
and then was poured onto ice (20 g). The organic layer was
separated and the aqueous layer was extracted with CH2Cl2
(3 × 20 mL). The combined organic extracts were washed
with brine (60 mL) and dried over sodium sulfate. Removal
of the solvent in vacuo gave an orange oil (0.3 g) that was
purified by flash chromatography (hexanes; CH2Cl2). The ti-
tle compound 5 was obtained as a yellow oil. Yield: 44 mg,
0.32 mmol, 64%. Rf 0.16 (CH2Cl2–EtOAc, 10:1). UV
1
2 Torr). H NMR (CDCl3) δ: 4.62–4.69 (m, 1H), 4.41–4.43
(m, 2H), 2.07 (s, 3H), 1.80–2.06 (m, 2H), 1.03 (t, J =
7.2 Hz, 3H). 13C NMR (CDCl3) δ: 170.5, 87.8, 63.8, 23.9,
20.8, 10.2.
2-Nitro-1-butene (2) (Caution: Lachrymator and foul
smelling)
(EtOH) λmax (nm): 208, 250, 302. IR (PTFE, cm–1) υmax
:
3257 (NH), 2960, 2920, 2851, 1633 (C=O), 1568, 1479,
1432, 1397, 1322. 1H NMR (CDCl3) δ: 9.82 (br s, 1H),
6.77–6.87 (m, 2H), 2.52 (q, 2H, J = 7.5 Hz), 2.42 (s, 3H),
1.17–1.26 (m, 3H). 13C NMR (CDCl3) δ: 188.1, 132.0,
128.6, 122.8, 116.5, 25.5, 20.0, 15.4. MS m/z (%): 138 (M+ +
1), 137 (M+), 122 (100%), 104, 94, 77, 67. HRMS m/z calcd.
for C8H11NO: 137.0841 (M+); found: 137.0841.
A modification of the literature procedure for the synthe-
sis of 2-nitropropene was utilized (17). A round-bottomed
flask (100 mL) fitted with a Vigreux column and short-path
distillation apparatus was charged with 2-nitro-1-butanol
(11.9 g, 0.100 mol) and phthalic anhydride (29.6 g,
0.200 mol) and was partially evacuated (under water aspira-
tor pressure). The reaction mixture was heated in an oil bath
to 150 °C for 30 min and then to 200 °C. The desired prod-
uct 2 distilled over with water into an ice-cooled receiving
flask. The aqueous layer was separated and the organic layer
was dried over sodium sulfate. The desired product 2 was
obtained as a blue-green oil. Yield: 4.48 g, 0.0443 mol,
44%; bp 76–84 °C at 40 Torr (lit. value (12) bp 108 °C at 61
Torr). IR (neat, cm–1) υma1x: 3132, 2980, 2942, 2882, 1524,
1465, 1436, 1347, 1258. H NMR (CDCl3) δ: 6.44 (s, 1H),
5.55 (s, 1H), 2.64 (q, J = 7.2 Hz, 2H,), 1.18 (t, J = 7.2 Hz,
3H,). 13C NMR (CDCl3) δ: 159.8, 116.3, 23.6, 11.8.
2-Acetyl-3-ethylpyrrole (8)
To a rt stirred solution of 3-ethyl-2-acetyl-1-(phenyl-
sulfonyl)pyrrole (14) (83 mg, 0.30 mmol) dissolved in meth-
anol (5 mL) was added potassium carbonate (170 mg,
1.2 mmol) and the reaction mixture was heated to reflux for
7 h and then allowed to cool to rt. Removal of the solvent in
vacuo gave an orange oil (0.5 g) that was partitioned be-
tween distilled water (20 mL) and ether (20 mL). The or-
ganic layer was separated and the aqueous layer was
extracted with ether (2 × 20 mL). The combined organic ex-
tracts were washed with brine (60 mL) and dried over so-
dium sulfate. Removal of the solvent in vacuo gave a yellow
oil (40 mg) that was purified by flash chromatography (hex-
anes; CH2Cl2). The desired product 8 was obtained as a light
yellow amorphous solid. Yield: 32 mg, 0.23 mmol, 78%; mp
64 to 65 °C. Rf 0.18 (CH2Cl2). UV (EtOH) λmax (nm): 206,
292. IR (PTFE, cm–1) υmax: 3271 (NH), 2967, 1622 (C=O),
4-Ethyl-2-(p-toluenesulfonyl)pyrrole (4)
To a rt stirred solution of 2-nitro-1-butene (2) (202 mg,
2.00 mmol) and tosylmethyl isocyanide (3) (586 mg,
3.00 mmol) dissolved in THF (3 mL) and 2-propanol (3 mL)
was added a solution of DBU (457 mg, 3.00 mmol) dis-
solved in THF (3 mL) and 2-propanol (3 mL). The reaction
mixture was stirred at rt for 20 h. Removal of the solvent in
vacuo gave a brown oil (1.8 g) that was purified by flash
1
1532, 1478, 1407, 1325, 1201, 1136. H NMR (CDCl3) δ:
© 2006 NRC Canada

Pelkey and Gribble
1341
9.43 (br s, 1H), 6.92–6.94 (m, 1H), 6.17–6.19 (m, 1H), 2.82
(q, 2H, J = 7.5 Hz), 2.47 (s, 3H), 1.30 (t, 3H, J = 7.5 Hz).
13C NMR (CDCl3) δ: 187.9, 134.2, 123.3, 111.5, 111.4, 28.0,
21.3, 15.1. MS m/z (%): 138 (M+ + 1), 137 (M+), 122
(100%), 94, 80, 67. HRMS m/z calcd. for C8H11NO:
137.0841 (M+); found: 137.0842.
C18H14N2O3S: C 63.89, H 4.17, N 8.28, S 9.47; found: C
64.04, H 4.07, N 8.20, S 9.34.
2-Methyl-1-propyl 2,4-dihydro-3-(p-toluenesulfonyl)pyr-
rolo[3,4-b]indole-4-carboxylate (13)
To a rt stirred solution of 2-methyl-1-propyl 3-nitroindole-
1-carboxylate (12) (18) (1.84 g, 7.00 mmol) and tosylmethyl
isocyanide (3) (1.56 g, 8.00 mmol) dissolved in THF
(50 mL) was added DBU (1.22 g, 8.00 mmol) and the reac-
tion mixture was stirred at rt for 20 h. Removal of the sol-
vent in vacuo gave a brown oil (4 g) that was purified by
flash chromatography (hexanes; CH2Cl2–hexanes, 3:1;
CH2Cl2). The desired product 13 was obtained as a brown
amorphous solid (615 mg, 1.50 mmol, 21%) that was puri-
fied by a second round of column chromatography (hexanes;
CH2Cl2–hexanes, 1:1). The yellow powder thus obtained
was recrystallized (CH2Cl2–hexanes) to give 13 as fine yel-
low needles; mp 177 to 178 °C. Rf 0.23 (CH2Cl2). UV
(EtOH) λmax (nm): 206, 222 (sh), 254 (sh), 278, 315 (sh),
324. IR (PTFE, cm–1) υmax: 3283 (NH), 2958, 1731 (C=O),
1,8-Dihydro-4-(phenylsulfonyl)-2-(p-toluenesulfonyl)pyr-
rolo[2,3-b]indole (10)
To a stirred solution of 3-nitro-1-(phenylsulfonyl)indole
(9) (18) (151 mg, 0.500 mmol) dissolved in THF (10 mL)
was added a solution of tosylmethyl isocyanide (3) (117 mg,
0.600 mmol) dissolved in THF (5 mL) followed by neat
DBU (183 mg, 1.20 mmol). The clear yellow reaction mix-
ture was stirred at rt for 22 h. Removal of solvent in vacuo
gave a crude orange oil (500 mg) that was purified by flash
chromatography (hexanes; CH2Cl2–hexanes, 3:1; CH2Cl2).
The desired product 10 was obtained as a white amorphous
solid (150 mg). Trituration (hexanes, 2 × 5 mL) gave 10 as a
gray flaky solid. Yield: 142 mg, 0.315 mmol, 63%; mp 212–
214 °C (dec). Two recrystallizations (CH2Cl2–cyclohexane,
2:1) gave 10 as white crystals; mp 236–238 °C. Rf 0.50
(CH2Cl2). UV (EtOH) λmax (nm): 210, 274 (sh), 300, 346
(sh). IR (KBr, cm–1) υmax: 3256 (NH), 2928, 1540, 1528,
1447, 1419, 1374, 1318, 1181. 1H NMR (CDCl3) δ: 9.78 (bs,
1H), 7.88–7.92 (m, 3H), 7.74–7.76 (m, 2H), 7.48–7.54 (m,
2H), 7.22–7.37 (m, 6H), 7.11 (d, 1H, J = 1.8 Hz), 2.41 (s,
3H). 13C NMR (CDCl3) δ: 144.3, 139.6, 138.5, 137.6, 136.4,
134.8, 130.2, 129.6, 128.8, 127.2, 126.9, 125.0, 124.6,
124.3, 120.1, 114.8, 113.4, 107.6, 21.8. MS m/z (%): 473.1
(M + Na)+. Anal. calcd. for C23H18N2O4S2: C 61.32, H 4.03,
N 6.22, S 14.23; found: C 61.35, H 4.04, N 6.23, S 14.36.
1
1595, 1515, 1448, 1417, 1379, 1317, 1199, 1139. H NMR
(CDCl3) δ: 9.60 (br s, 1H), 8.32 (br s, 1H), 8.24–8.26 (m,
1H), 7.89 (d, 2H, J = 8.1 Hz), 7.34–7.49 (m, 2H), 7.24 (d,
2H, J = 8.1 Hz), 7.03 (br s, 1H), 4.23 (d, 2H, J = 4.8 Hz),
2.35 (s, 3H), 2.14 (br s, 1H), 1.06 (d, 6H, J = 6.6 Hz). 13C
NMR (CDCl3) δ: 151.4, 144.2, 143.2, 139.7, 131.4, 130.1,
127.4, 126.6, 123.8, 122.8, 121.5, 120.0, 116.1, 115.5,
107.2, 73.1, 28.1, 21.7, 19.3. HRMS m/z calcd. for
C22H22N2O4S: 410.1300 (M+); found: 410.1294. Anal. calcd.
for C22H22N2O4S: C 64.37, H 5.40, N 6.82, S 7.81; found: C
64.46, H 5.51, N 6.85, S 7.76.
2-Methyl-1-propyl 2,4-dihydro-3-valerylpyrrolo[3,4-b]-
indole-4-carboxylate (14)
2-Acetyl-1,8-dihydro-8-(phenylsulfonyl)pyrrolo[2,3-b]-
indole (11)
To a 0 °C stirred suspension of aluminum chloride
(200 mg, 1.50 mmol) in CH2Cl2 (5 mL) was added freshly
distilled (from 0.1% quinoline) valeryl chloride (72 mg,
0.60 mmol) and this was stirred for 15 min. The reaction
mixture was treated with a solution of 2-methyl-1-propyl
2,4-dihydro-3-(p-toluenesulfonyl)pyrrolo[3,4-b]indole-1-car-
boxylate (13) (123 mg, 0.300 mmol) dissolved in CH2Cl2
(10 mL) dropwise. The reaction mixture was stirred at 0 °C
for 15 min and then was poured onto ice (20 g). The aque-
ous solution was extracted with CH2Cl2 (3 × 30 mL) and the
combined organic extracts were washed with a saturated
aqueous solution of sodium bicarbonate (100 mL) and brine
(100 mL) and dried over sodium sulfate. Removal of the sol-
vent in vacuo gave a tan amorphous solid (0.2 g) that was
purified by flash chromatography (hexanes; CH2Cl2–hexanes,
1:1; CH2Cl2–hexanes, 3:1). The desired product 14 was ob-
tained as an off-white amorphous solid (68 mg, 0.20 mmol,
67%, mp 166–168 °C). Recrystallization (EtOAc–hexanes)
gave 14 as white needles; mp 173 to 174 °C. Rf 0.48 (H2Cl2–
MeOH, 98:2). UV (EtOH) λmax (nm): 206, 233 (sh), 246
(sh), 277 (sh), 286, 311 (sh), 344 nm. IR (KBr) υmax (cm–1):
3236 (NH), 2956, 2870, 1728 (C=O), 1627 (C=O), 1506,
To a 0 °C stirred suspension of aluminum chloride in
CH2Cl2 (5 mL) was added acetyl chloride (79 mg,
1.0 mmol) and the mixture was stirred for 15 min. The reac-
tion mixture was treated with a solution of 1,8-dihydro-2-(p-
toluenesulfonyl)-4-(phenylsulfonyl)pyrrolo[2,3-b]indole (10)
(225 mg, 0.500 mmol) dissolved in CH2Cl2 (5 mL). The re-
action mixture was stirred at 0 °C for 2 h and then at rt for
30 min. The reaction was poured onto ice (20 g) and ex-
tracted with CH2Cl2 (3 × 30 mL). The combined organic ex-
tracts were washed with a saturated aqueous solution of
sodium bicarbonate (100 mL) and brine (100 mL) and dried
over sodium sulfate. Removal of the solvent in vacuo gave a
yellow oil (0.6 g) that was purified by flash chromatography
(hexanes; CH2Cl2–hexanes, 1:1; CH2Cl2–hexanes, 3:1). The
desired product 11 was obtained as a white amorphous solid.
Yield: 82 mg, 0.24 mmol, 48%; mp 222–225 °C. Recry-
stallization (CH2Cl2–hexanes) gave 11 as light brown crys-
tals; mp 230 to 231 °C. Rf 0.18 (CH2Cl2). UV (EtOH) λmax
(nm): 206, 224, 254 (sh), 332. IR (PTFE, cm–1) υmax: 3304
(NH), 2917, 2851, 1633, 1555, 1488, 1440, 1380, 1285,
1
1201, 1171. H NMR (CDCl3) δ: 9.87 (br s, 1H), 7.93–7.96
1
(m, 1H), 7.81–7.85 (m, 2H), 7.27–7.59 (m, 6H), 7.11 (d, 1H,
J = 1.5 Hz), 2.51 (s, 3H). 13C NMR (CDCl3) δ: 187.9, 139.1,
139.0, 136.9, 134.7, 132.9, 129.6, 127.0, 124.9, 124.7,
124.4, 120.0, 114.9, 113.5, 108.2, 25.3. MS m/z (%): 338
(M+), 197 (100%), 169, 155, 127, 101, 77. Anal. calcd. for
1460, 1402, 1390, 1319, 1268, 1219. H NMR (CDCl3) δ:
10.04 (br s, 1H), 8.43 (br s, 1H), 8.00–8.02 (m, 1H), 7.43–
7.48 (m, 1H), 7.33–7.38 (m, 1H), 7.13 (br s, 1H), 4.27 (d,
2H, J = 6.3 Hz), 3.12 (t, 2H, J = 7.2 Hz), 2.12–2.22 (m, 1H),
1.82–1.92 (m, 2H), 1.48–1.60 (m, 2H), 1.10 (d, 6H, J =
© 2006 NRC Canada

1342
Can. J. Chem. Vol. 84, 2006
6.9 Hz), 1.02 (t, 3H, J = 7.2 Hz). 13C NMR (CDCl3) δ:
190.1, 151.6, 143.4, 131.8, 126.8, 123.5, 122.6, 122.5,
121.0, 118.5, 116.3, 107.5, 73.2, 40.5, 28.2, 26.7, 22.8, 19.4,
14.3. MS m/z (%): 340 (M+, 100%), 298, 283, 242, 198,
183, 156, 127, 101, 77. Anal. calcd. for C20H24N2O3: C
70.57, H 7.11, N 8.23; found: C 70.32, H 7.11, N 8.13.
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Acknowledgements
dron Lett. 28, 4123 (1987).
The authors would like to acknowledge the Donors of the
Petroleum Research Fund (PRF), administered by the Amer-
ican Chemical Society, Pfizer, and Wyeth-Ayerst, for support
of this project, Smith-Kline Beecham for sponsoring a Divi-
sion of Organic Chemistry American Chemical Society Grad-
uate Fellowship to ETP, and Professor Daniel M. Ketcha
(Wright State University, Dayton, Ohio) for a gift of 8.
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© 2006 NRC Canada