Rearrangement of indolinesulfonamides to sulfones using polyphosphoric acid (PPA)

Article abstract of DOI:10.1080/00397910903161868

Unlike other N-alkylsulfonanilides, indolinesulfonamides hydrolyze in 98% sulfuric acid. Recent work in this laboratory has shown that rearrangement can be achieved by using polyphosphoric acid. A series of substituted indolinesulfonamides has been prepar

Full text of DOI:10.1080/00397910903161868

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Rearrangement of Indolinesulfonamides
to Sulfones Using Polyphosphoric Acid
(PPA)
Brian Raszka a , James McKee a & Murray Zanger a
a Department of Chemistry and Biochemistry, University of the
Sciences in Philadelphia, Philadelphia, Pennsylvania, USA
Version of record first published: 17 May 2010.
To cite this article: Brian Raszka , James McKee & Murray Zanger (2010): Rearrangement of
Indolinesulfonamides to Sulfones Using Polyphosphoric Acid (PPA), Synthetic Communications: An
International Journal for Rapid Communication of Synthetic Organic Chemistry, 40:12, 1837-1846
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Synthetic Communications1, 40: 1837–1846, 2010
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910903161868
REARRANGEMENT OF INDOLINESULFONAMIDES TO
SULFONES USING POLYPHOSPHORIC ACID (PPA)
Brian Raszka, James McKee, and Murray Zanger
Department of Chemistry and Biochemistry, University of the Sciences in
Philadelphia, Philadelphia, Pennsylvania, USA
Unlike other N-alkylsulfonanilides, indolinesulfonamides hydrolyze in 98% sulfuric acid.
Recent work in this laboratory has shown that rearrangement can be achieved by using
polyphosphoric acid. A series of substituted indolinesulfonamides has been prepared and
rearranged to their corresponding indoline arylsulfones.
Keywords: Indoline; phenylsulfonylindoline; polyphosphoric acid
INTRODUCTION
Diaryl sulfones have been shown to function as nonnucleoside reverse
transcription inhibitors (NNRTIs) of HIV.[1] In an ongoing effort to prepare novel
sulfones for possible use against AIDS, the 98% sulfuric acid–catalyzed rearrange-
ment of N-alkyl benzene sulfonanilides has been successfully carried out on a large
number of diarylsulfonamides with substitutents on either or both of the aromatic
rings.[2] The reaction’s scope was broadened to include anilines in which the nitrogen
was tied back to its ring by an alkyl group, for example, tetrahydroquinoline[3]
(THQ) and 2,3,4,5-tetrahydro-1H-1-benzazepine.[4] However, when indolinesulfona-
mides were treated with 98% sulfuric acid, only hydrolysis products resulted.[4] No
explanation for this anomaly is forthcoming.
As part of another approach to preparing heterocyclic aryl sulfones, the
reaction of benzene or toluenesulfonic acid with arenes in polyphosphoric acid
(PPA) was studied. For example, when p-xylene, p-toluenesulfonic acid, and
PPA were heated at 130ꢀC, a good yield of 1,4-dimethyl-2-[(4-methylphenyl)sul-
fonyl]benzene resulted[5] (Fig. 1a). A similar reaction using toluenesulfonic acid
and THQ failed (Fig. 1b). Suspecting that the weakly basic nitrogen atom in
THQ might have interfered with the reaction, 1-(phenylsulfonyl)indoline (3), in
which the nitrogen is protected, was used instead (Fig. 1c). A sulfone product
was isolated; however, when it was analyzed by NMR, the product did not
Received May 26, 2009.
Address correspondence to Murray Zanger, Department of Chemistry and Biochemistry,
University of the Sciences in Philadelphia, 600 S. 43rd Street, Philadelphia, PA, 19104-4416, USA.
E-mail: m.zanger@usp.edu
1837

1838
B. RASZKA, J. MCKEE, AND M. ZANGER
Figure 1. Background for indolinesulfonamide rearrangements.
possess the p-methyl group. What in fact had happened was that the benzenesul-
fonyl group attached to the nitrogen had migrated (rearranged) to the o-position
on the THQ. The toluenesulfonic acid did not participate in the reaction.
Having uncovered a novel method for achieving sulfonamide rearrangements,
this technique (PPA) was tried on 1-(phenylsulfonyl)indoline, (3). PPA and the indo-
line amide were heated at 100ꢀC for periods ranging from 1 to 24 h (Fig. 1d). The hot
reaction mixture was quenched in ice water, and the resulting solid was filtered and
analyzed. The product of these reactions consisted of some unreacted starting
material and rearranged product, 7-(phenylsulfonyl)-indoline (10). This article
describes the synthesis and rearrangement of indoline sulfonamides.
RESULTS AND DISCUSSION
For this work, the syntheses of substituted indoline sulfones, which paralleled
those prepared from terahydroquinoline and 2,3,4,5-tetrahydro-1H-1-benzazepine,
were desired. This required the synthesis of indoline or indoline derivatives
with methyl and chloro-groups on the 5-position (Scheme 1). The preparation of

REARRANGEMENT OF INDOLINESULFONAMIDES TO SULFONES
1839
Scheme 1. Syntheses of 5-substituted indoline=indolinesulfonamide.
5-methylindoline[6] (2) was achieved by the reduction of 5-methylindole using sodium
cyanoborohydride. The 5-chloroindoline amide (6) was prepared by chlorination of
the 1-(4-methylphenylsulfonyl)indoline (4) using sulfuryl chloride.[4]
The indolinesulfonamides were prepared by reaction of the indolines with
benzenesulfonyl chloride, p-tolylsulfonyl choride, or 2-nitrobenzenesulfonyl chloride
to give 3–5, 8, and 9. This was followed by chlorination of 4 and 5, which gave
compounds 6 and 7 (Scheme 2). Of the amides, 3–5 and 8 were known, whereas
for the sulfones, only 11 is known. Table 1 lists the sulfonamides and sulfones that
were prepared and characterized.
Scheme 2. (i) R1R2BzSO2Cl, 10% NaOH, warm to 50ꢀC; (ii) PP at 140ꢀC for 2 h, pour into ice water.

1840
B. RASZKA, J. MCKEE, AND M. ZANGER
Table 1. Preparation of sulfonamides and sulfones
No.
Type
R1
R2
R3
Mp (ꢀC)
Formula
Yield (%)
3a
4b
5c
I
I
H
CH3
H
H
H
H
H
131–132
100.5–101.5
106–107
120–121
158–159
99–100
C14H13NO2S
C15H15NO2S
C14H12N2O4S
C15H14ClNO2S
C14H11ClN2O4S
C16H17NO2S
C15H14N2O4S
95
72
72
78
83
62
59
40
20
33
20
50
33
25
I
NO2
H
H
Cl
6
I
CH3
H
7
I
NO2
H
Cl
8d
9
I
CH3
H
CH3
CH3
H
I
NO2
H
142–143
114–116
134–135
141–142
154–155
184–185
133–134
167–168
10
11e
12
13
14
15
16
II
II
II
II
II
II
II
H
C14H13NO2S
CH3
H
H
H
C15H15NO2S
C14H12N2O4S
C15H14ClNO2S
C14H11ClN2O4S
C16H17NO2S
C15H14N2O4S
NO2
H
H
Cl
CH3
H
NO2
H
Cl
CH3
H
CH3
CH3
NO2
aCompound 3 is known: Ref. 7 (mp 129.5–131).
bCompound 4 is known: Ref 8 (mp 100.5–101.5).
cCompound 5 is known: Ref. 9 (no mp reported).
dCompound 8 is known: Ref. 10 (mp 75–77).
eCompound 11 is known: Ref. 11 (mp 135–136).
EXPERIMENTAL
Chemicals were purchased from Sigma-Aldrich Chemical Co. and were used
without further purification. Reactions were monitored using Analtech Inc. silica-gel
60 GF analytical thin-layer chromatography (TLC) plates and analyzed with 254-nm
ultraviolet (UV) light. Silica gel for column chromatography was 60–200 mesh.
Melting points were obtained with a Stanford Research Systems’ Optimelt automatic
1
melting-point device without correction. H and 13C NMR spectra were obtained
in CDCl3 (sulfonamides) and d6-acetone (sulfones) on a Bruker Avance 400
NMR spectrometer operating at 400 MHz for 1H and 100 MHz for 13C. All infrared
spectra (FT-IR) were recorded as thin films on KBr plates or in KBr pellets. All mass
spectra were determined with a gas chromatography–mass spectrometry (GC-MS)
instrument.

REARRANGEMENT OF INDOLINESULFONAMIDES TO SULFONES
1841
Preparation of 5-Methylindoline[6] (2)
Acetic acid (AcOH; 1 mL) and sodium cyanoborohydride (0.53 g, 8.36 mmol,
1.1 eq) were added to a vial equipped with a magnetic stir bar. The vial was chilled
in a waterbath and sealed with a rubber septum. The reaction was run under nitro-
gen gas. 5-Methylindole (1.0 g, 7.6 mmol, 1 eq) was dissolved in AcOH (0.5 mL) and
transferred to the vial via a syringe. The reaction was left stirring under nitrogen at
14ꢀC (ꢁ2 h) and was monitored by TLC 2:1 hexane=ethyl acetate. The reaction was
quenched over ice (10 ꢂ volume) and a KOH=H2O (50% wt=vol, 5 mL) slurry. The
product was extracted using ethyl acetate and dried over magnesium sulfate. It
was purified by column chromatography. The product, 5-methylindoline 2 (0.60 g,
60% isolated yield), was isolated as a yellow oil. This oil was used as starting material
to form the 5-methylindoline sulfonamides. No analytical data was accumulated for
this intermediate.
Preparation of 1-(Phenylsulfonyl)indoline (3)
Benzenesulfonyl chloride (17.6 g, 0.1 mol) was added to a magnetically stirred
solution of indoline (11.9 g, 0.1 mol) at room temperature for 30 min, followed by the
addition of 10% NaOH (5 mL). The mixture was stirred for an additional 10 min
while the pH was kept alkaline. The reaction mixture was allowed to sit for
30 min. The solid was collected using suction filtration and was washed with H2O
(3 ꢂ 100 mL). The solid was allowed to air dry. The crude product was recrystallized
(95% EtOH) to give 1-(phenylsulfonyl)indoline 3 (24.6 g, 95%) as fine white crystals:
mp 132–133ꢀC (lit. 131–132ꢀC); IR (thin film) 1351.77 cmꢃ1 (SO2 asym str.),
1
1168.30 cmꢃ1 (SO2 sym str.); H (400 MHz, DMSO-d6): d 7.82 (d, J ¼ 8.0, 2H),
7.66 (t, J ¼ 8.0, 1H), 7.55 (t, J ¼ 8.0, 2H), 7.50 (d, J ¼ 8.0, 1H), 7.20 (t, J ¼ 8.0
1H), 7.14 (d, J ¼ 8.0 1H), 6.98 (t, J ¼ 8.0, 1H), 3.90 (t, J ¼ 8.0, 2H), 2.82 (t, J ¼ 80,
2H); 13C NMR (100 MHz, DMSO-d6): d 142.11, 136.99, 134.57, 134.30, 132.98,
130.54, 130.30, 130.04, 128.38, 128.24, 127.97, 127.65, 126.32, 124.67, 115.06,
50.83, 28.08; MS m=z 259.
Preparation of 1-[(4-Methylphenyl)sulfonyl]indoline (4)
p-Toluenesulfonyl chloride (19.1 g, 0.1 mol) was gradually added with stirring
to indoline (11.9 g, 0.1 mol) at room temperature, followed by the addition of 10%
NaOH (5 mL). The mixture was stirred for an additional 10 min while the pH was
kept alkaline. The reaction mixture was allowed to sit for 30 min. The solid was col-
lected using suction filtration and was washed with H2O (3 ꢂ 100 mL). The solid was
allowed to air dry. The crude product was recrystallized (95% EtOH) to give
1-[(4-methylphenyl)sulfonyl]indoline 4 (19.6 g, 72%) as fine white crystals: mp
100.5–101.5ꢀC (lit. 100.5–101.5ꢀC); IR (KBr pellet): 1349.13 cmꢃ1 (SO2 asym str.),
1
1167.25 cmꢃ1 (SO2 sym str.) cmꢃ1; H (400 MHz, CDCl3): d 7.68 (d, J ¼ 8.6, 3H),
7.24 (m, J ¼ 8.6, 3H), 7.10 (d, J ¼ 7.3, 1H), 6.99 (t, J ¼ 7.4, 1H), 3.93 (t, J ¼ 8.4,
2H), 2.90 (t, J ¼ 8.4, 2H), 2.39 (s, 3H); 13C NMR (100 MHz, CDCl3): d 144.45,
142.39, 132.17, 130.06, 128.10, 127.72, 125.51, 124.12, 115.41, 77.79, 77.47, 77.15,
50.35, 28.27, 21.94; MS m=z 273.

1842
B. RASZKA, J. MCKEE, AND M. ZANGER
Preparation of 1-[(2-Nitrophenyl)sulfonyl]indoline (5)
o-Nitrobenzenesulfonyl chloride (22.2 g, 0.1 mol) was gradually added with
stirring to indoline (11.9 g, 0.1 mol) at room temperature, followed by the addition
of 10% NaOH (5 mL). The mixture was stirred for an additional 10 min while the
pH was kept alkaline. The reaction mixture was allowed to sit for 30 min. The solid
was collected using suction filtration and was washed with H2O (3 ꢂ 100 mL). The
solid was allowed to air dry. The crude product was recrystallized (95% EtOH) to
give 1-[(2-nitrophenyl)-sulfonyl]indoline 5 (27.3 g, 72%) as fine white crystals: mp
106–107ꢀC; IR (KBr pellet): 1541.69 cmꢃ1 (NO2 asym str.), 1357.84 cmꢃ1 (NO2
sym str.), 1242.94 cmꢃ1 (SO2 asym str.), 1164.20 cmꢃ1 (SO2 sym str.); 1H
(400 MHz, CDCl3): d 7.96 (d, J ¼ 7.8, 1H), 7.70 (t, J ¼ 8.4, 1H), 7.63 (m, J ¼ 8.4,
2H), 7.48 (d, J ¼ 8.0, 1H), 7.20 (m, J ¼ 7.5, 8.0, 2H), 7.05 (t, J ¼ 7.5, 1H), 4.20
(t, J ¼ 8.4, 2H), 3.10 (t, J ¼ 8.4, 2H); 13C NMR (100 MHz, CDCl3): d 141.47,
134.37, 132.01, 130.67, 128.19, 125.88, 124.62, 114.92, 77.76, 77.65, 77.44, 77.13,
50.86, 28.44; MS m=z 304.
Preparation of 5-Chloro-1-[(4-methylphenyl)sulfonyl]indoline (6)
Sulfuryl chloride (5.0 g, 37 mmol) was added to a magnetically stirred solution
of indoline-p-toluenesulfonamide 4 (6.19 g, 20.4 mmol) in benzene (50 mL) at room
temperature. A condenser was fitted to the round-bottomed flask, and the reaction
mixture was heated to reflux for 3–5 h. The reaction mixture was monitored by
TLC (20:1 CH2Cl2=MeOH). A Dean–Stark trap was fitted to the apparatus to help
remove any excess sulfuryl chloride. Excess benzene (10 mL) was added to the
round-bottomed flask, and the mixture was refluxed to remove the excess sulfuryl
chloride. The reaction mixture was allowed to cool, and the benzene was removed
in vacuo. The product was triturated with cold methanol (20 mL) and was recrystal-
lized (isopropyl alcohol) to give 5-chloro-1-[(4-methylphenyl)-sulfonyl]indoline 6
(4.83 g, 78%) as white needles: mp 120–121ꢀC; IR (KBr pellet): 1161.53 cmꢃ1 (SO2
1
sym str.); H: (400 MHz, CDCl3) d 7.67 (d, J ¼ 8.6, 2H), 7.58 (d, J ¼ 8.6, 1H), 7.26
(d, J ¼ 8.6, 2H), 7.18 (d, J ¼ 8.6, 1H), 7.06 (s, 1H), 3.93 (t, J ¼ 8.4, 2H), 2.88 (t,
J ¼ 8.5, 2H), 2.40 (s, 3H); 13C NMR (100 MHz): d 144.74, 141.18, 134.13, 134.07,
130.17, 129.31, 127.70, 125.70, 116.35, 77.75, 77.43, 77.11, 50.54, 28.11, 21.96; MS
m=z 308.
Preparation of 5-Chloro-1-[(2-nitrophenyl)sulfonyl]indoline (7)
Sulfuryl chloride (5.0 g, 37 mmol) was added to a magnetically stirred sol-
ution of indoline-o-nitrobenzenesulfonamide 5 (6.19 g, 18.3 mmol) in benzene
(50 mL) at room temperature. A condenser was fitted to the round-bottomed flask,
and the reaction mixture was heated to reflux for 3–5 h. The reaction mixture was
monitored by TLC (20:1 CH2Cl2=MeOH). A Dean–Stark trap was fitted to the
apparatus to help remove any excess sulfuryl chloride. Excess benzene (10 mL)
was added to the round-bottomed flask, and the mixture was refluxed to draw
off the excess sulfuryl chloride. The reaction mixture was allowed to cool, and
the benzene was removed in vacuo. The product was triturated with cold methanol

REARRANGEMENT OF INDOLINESULFONAMIDES TO SULFONES
1843
(20 mL) and was recrystallized (isopropyl alcohol) to give 5-chloro-1-[(2-o-nitro-
phenyl)sulfonyl]indoline (5.12 g, 83%) as white fine white crystals: mp
7
158–159ꢀC; IR (KBr pellet): 1544.61 cmꢃ1 (NO2 asym str.), 1377.78 cmꢃ1 (NO2
sym str.), 1364.01 cmꢃ1 (SO2 asym str.), 1174.07 cmꢃ1 (SO2 sym str.); 1H
(400 MHz, CDCl3): d 7.96 (d, J ¼ 8.6, 1H), 7.74 (t, J ¼ 8.2, 1H), 7.66 (m, J ¼ 8.2,
8.6, 2H), 7.39 (d, J ¼ 8.2, 1H), 7.16 (d, J ¼ 8.6, 1H) 7.15 (s, 1H), 4.10 (t, J ¼ 8.4,
2H), 3.08 (t, J ¼ 8.4, 2H); 13C NMR: (100 MHz, CDCl3) d 140.23, 134.63,
134.08, 132.11, 129.84, 128.18, 126.05, 124.74, 115.85, 77.76, 77.44, 77.12, 51.06,
28.30; MS m=z 338.
Preparation of 5-Methyl-1-[(4-methylphenyl)sulfonyl]indoline (8)
In a vial equipped with a magnetic stir bar, 5-methylindoline 2 (0.30 g,
2.25 mmol) was added along with base (K2CO3=H2O, 1 g=mL, 1 mL). Tosyl chloride
(0.24 g, 2.25 mmol) was dissolved in CH2Cl2 and pipetted into the vial. The reaction
was stirred at room temperature and was monitored by TLC (2:1 hexane=ethyl acet-
ate, product Rf ¼ 0.49). The product was extracted and washed with brine. The
organic phase was dried over magnesium sulfate and filtered, and the solvent was
removed in vacuo. The crude solid was purified by column chromatography
(hexane=ethyl acetate, silica gel, gradient 0–100%). The product, 5-methyl-1-
[(4-methylphenyl)sulfonyl]indoline 8 (0.40 g, 62% isolated yield)ꢃw1as a white powder:
mp 99–100.5ꢀC (lit.[4] 75–77ꢀC); IR: (thin film) 1352.44 cm
(SO2 asym str.),
1164.29 cmꢃ1 (SO2 sym str.); H (400 MHz, CDCl3): 7.66 (d, J ¼ 8.2, 2H), 7.48 (d,
J ¼ 8.1, 1H), 7.23 (d, J ¼ 8.2, 2H), 6.89 (d, J ¼ 8.1, 1H), 6.59 (s, 1H), 3.81 (t,
J ¼ 8.5, 2H), 2.50 (t, J ¼ 8.5, 2H), 2.32 (s, 3H), 2.24 (s, 3H); 13C NMR (100 MHz,
CDCl3): d 144.28, 140.04, 134.42, 133.86, 132.39, 129.99, 128.60, 127.75, 125.13,
115.40, 50.50, 28.29, 92.8, 21.27; MS m=z 287.
1
Preparation of 5-Methyl-1-[(2-nitrophenyl)sulfonyl]indoline (9)
5-Methyl indoline 3 (0.30 g, 2.3 mmol) was added with base (10% NaOH, 1 mL)
to a vial equipped with a magnetic stir bar. The 2-nitrobenzenesulfonyl chloride
(0.24 g, 2.3 mmol) was dissolved in CH2Cl2 (5 mL) and was pipetted into the vial.
The reaction was stirred at room temperature and monitored by TLC (2:1
hexane=ethyl acetate, product Rf ¼ 0.31). The product was extracted with ethyl acet-
ate and washed with brine. The organic phase was dried over magnesium sulfate.
The solvent was removed in vacuo. The crude solid was purified by column chroma-
tography (hexane=ethyl acetate, silica gel, gradient 0–100%). The product,
5-methyl-1-[(2-nitrophenyl)-sulfonyl]indoline 9 (0.42 g, 59% isolated yield) gave
white crystals: mp 142–143ꢀC; IR: (KBr Pellet) 1547.09 cmꢃ1 (NO2 asym str.),
1377.79 cmꢃ1 (NO2 sym str.), 1358.69 cmꢃ1 (SO2 asym str.), 1175.05 cmꢃ1 (SO2
1
sym str.); H (400 MHz, CDCl3): d 7.93 (d, J ¼ 8.6, 2H), 7.70 (t, J ¼ 8.2, 1H), 7.65
(m, J ¼ 8.6, 2H), 7.37 (d, J ¼ 8.5, 1H), 7.01 (d, J ¼ 7.9, 1H), 6.99 (s, 1H), 4.13 (t,
J ¼ 8.3, 2H), 3.03 (t, J ¼ 8.3, 2H), 2.31 (s, 3H); 13C NMR (101 MHz, CDCl3): d
139.11, 136.88, 134.49, 134.23, 131.89, 130.63, 128.66, 126.51, 124.51, 114.86,
77.75, 77.43, 77.11, 50.96, 28.46; MS m=z 318.

1844
B. RASZKA, J. MCKEE, AND M. ZANGER
General Procedure for the Formation of Indoline Sulfones
PPA (50 mL) was added to a 250-mL beaker equipped with a stir bar and mag-
netic stirrer. The PPA was heated to 130ꢀC and was stirred vigorously until the acid
became fluid. The sulfonamide (3.00 g) was added to the beaker in portions while
stirring steadily. A uniform dark green color appeared in less than 1 h. The reaction
was carried out for 3 h. The reaction was monitored by a thermometer (heat range
120–135ꢀC). The hot mixture was poured into H2O (75 mL) and was stirred vigor-
ously to avoid clumping. The precipitate was stirred for 15 min and then was filtered
through a fritted (medium porosity) funnel. Cold water (3 ꢂ 20 mL) was used to
wash the solid. The product was dried in a vacuum oven for 2 days. The product
was decolorized and purified using a Soxhlet extraction and CH2Cl2.
Preparation of 7-(Phenylsulfonyl)indoline (10)
Using the procedure described previously, the final compound 7-[(4-
methylphenyl)sulfonyl]indoline 10 (1.2 g, 40% isolated yield) was a white powder
that was intensely fluorescent under long UV light: mp 114–116ꢀC; IR: (thin film)
3409.87 cmꢃ1 (N-H str.), 1284.91 cmꢃ1 (SO2 asym str.), 1133.16 cmꢃ1 (SO2 sym
1
str.); H (400 MHz, DMSO-d6): d 7.94 (d, J ¼ 8.0, 2H), 7.59 (d, J ¼ 8.0, 2H), 7.57
(m, J ¼ 8.0, 1H), 7.35 (d, J ¼ 8.0, 1H), 7.18 (d, 1H), 6.58 (t, J ¼ 8.0, 1H), 6.45
(s, 1H-N), 3.60 (t, J ¼ 5.7, 2H), 2.92 (t, J ¼ 5.7, 2H); 13C NMR: (100 MHz,
DMSO-d6) d 151.03, 142.72, 134.14, 133.44, 130.24, 130.08, 127.39, 126.59, 117.54,
117.09, 47.52, 28.53; MS m=z 259.
Preparation of 7-[(4-Methylphenyl)sulfonyl]indoline (11)
As before, the final compound 7-[(4-methylphenyl)sulfonyl]indoline 11 (0.60 g,
20% isolated yield) was a white powder that was intensely fluorescent under long UV
light: mp 135ꢀC; IR (KBr pellet): 3401.50 cmꢃ1 (NꢃH str.), 1284.42 cmꢃ1 (SO2 asym
1
str.) 1132.03 cmꢃ1 (SO2 sym str.); H (400 MHz, acetone-d6): d 7.87 (d, J ¼ 8.6, 2H),
7.30 (m, J ¼ 8.5, 8.6, 3H), 7.21 (d, J ¼ 8.5, 1H), 6.63 (t, J ¼ 8.1, 1H), 6.02 (s, 1H), 3.70
(t, J ¼ 8.7, 2H), 3.01 (t, J ¼ 8.7, 2H), 2.41 (d, J ¼ 7.6, 3H); 13C NMR (100 MHz,
acetone-d6): d 151.04, 144.26, 140.41, 132.88, 130.04, 129.37, 127.14, 126.39,
118.94, 117.05, 47.21, 29.90, 20.88; MS m=z 273.
Preparation of 7-[(2-Nitrophenyl)sulfonyl]indoline (12)
The crude product was purified by column chromatography (hexane=ethyl
acetate, silica gel, gradient 0–100% ethyl acetate). This gave 7-[(2-
nitrophenyl)sulfonyl]indoline 12 (0.10 g,ꢃ313% isolated yield), a white solid: mp
141–142ꢀC; IR (KBr pellet): 3404.88 cm (NꢃH str.), 1542.43 cmꢃ1 (NO2 asym
str.), 1365.08 cmꢃ1 (NO2 sym str.), 1291.79 cmꢃ1 (SO2 asym str.), 1137.18 cmꢃ1 (SO2
1
sym str.); H (400 MHz, acetone-d6): d 8.4 (d, J ¼ 8.6, 1H), 7.95 (m, J ¼ 8.2, 8.2, 8.6,
3H), 7.40 (d, J ¼ 8.5, 1H), 7.26 (d, J ¼ 8.5, 1H), 6.68 (t, J ¼ 8.6, 1H), 6.06 (s, 1H),
3.76 (t, J ¼ 8.8, 2H), 3.08 (t, J ¼ 8.6, 2H); 13C NMR (100MHz, acetone-d6): d

REARRANGEMENT OF INDOLINESULFONAMIDES TO SULFONES
1845
135.09, 133.63, 132.60, 131.63, 130.97, 128.58, 128.23, 127.05, 126.19, 124.87, 47.48,
29.89; MS m=z 304.
Preparation of 5-Chloro-7-[(4-methylphenyl)sulfonyl]indoline (13)
The crude rearrangement product resulted in tan crystals weighing (0.88 g, 88%
crude yield). The product was recrystallized from isopropyl alcohol to give
5-chloro-7-[(4-methylphenyl)sulfonyl]indoline 13 (0.200 g, 20% isolated yield), a
white powder: mp 154–155ꢀC; IR (KBr pellet): 3413.67 cmꢃ1 (NꢃH str.),
1
1291.55 cmꢃ1 (SO2 asym str.), 1140.20 cmꢃ1 (SO2 sym str.); H (400 MHz, acetone-
d6): d 7.89 (d, J ¼ 8.6, 2H), 7.54 (s, 1H), 7.38 (d, J ¼ 8.6, 2H), 7.22 (s, 1H), 3.64 (t,
J ¼ 8.5, 2H), 2.88 (t, J ¼ 8.5, 2H), 2.41 (s, 3H); 13C NMR (400 MHz, acetone-d6):
d 149.85, 144.77, 139.68, 135.87, 130.22, 129.48, 127.30, 125.07, 120.67, 119.03,
47.48, 47.40, 29.90, 20.93; MS m=z 308.
Preparation of 5-Chloro-1-[(2-nitrophenyl)sulfonyl]indoline (14)
The crude rearrangement product resulted in light green crystals (0.93 g, 93%
crude yield). The product was purified by column chromatography (hexane=ethyl
acetate, silica gel, gradient 0–100% ethyl acetate). This resulted in 5-chloro-1-
[(2-nitrophenyl)sulfonyl]indoline 14 (0.500 g, 50% isolated yield) of yellow crystals:
mp 184–185ꢀC; IR (KBr pellet) 3409.51 cmꢃ1 (NꢃH str.), 2923.67 cmꢃ1 (CH2 asym
str.), 2853.77 cmꢃ1 (CH2 sym str.), 1541.55 cmꢃ1 (NO2 asym str.), 1375.32 cmꢃ1
(NO2 sym str.), 1293.56 cmꢃ1 (SO2 asym str.), 1164.83 cmꢃ1 (SO2 sym str.); 1H
(400 MHz, acetone-d6): d 8.40 (d, J ¼ 8.6, 1H), 7.97 (m, J ¼ 8.4, 3H), 7.35 (s, 1H),
7.29 (s, 1H), 6.22 (s, 1H), 3.75 (t, J ¼ 8.7, 2H), 3.11 (t, J ¼ 8.7, 2H); 13C NMR
(100 MHz, acetone-d6): d 150.88, 136.27, 135.64, 134.11 132.91, 131.25, 130.25,
125.84, 125.19, 120.36, 116.48, 47.60, 29.90; MS m=z 338.
Preparation of 5-Methyl-7-[(4-methylphenyl)sulfonyl]indoline (15)
The product was extracted with ethyl acetate. The organic phase was dried over
magnesium sulfate, and the solvent was removed in vacuo. The crude product was
purified by column chromatography (hexane=ethyl acetate, gradient 0–100% ethyl
acetate). The resulting yield was 5-methyl-7-[(4-methylphenyl)sulfonyl]indoline 15
(0.10 g, 33% isolated yield), a white powder: mp 133–134ꢀC; IR (KBr pellet):
3418.09 cmꢃ1 (NꢃH str.), 1289.52 cmꢃ1 (SO2 asym str.), 1145.39 cmꢃ1 (SO2 sym
1
str.); H (400 MHz, acetone-d6): d 7.86 (d, J ¼ 8.3, 2H), 7.38 (d, J ¼ 8.0, 2H), 7.22
(s, 1H), 7.05 (s, 1H), 5.84 (s, 1H), 3.67 (t, J ¼ 8.6, 2H), 2.97 (t, J ¼ 8.6, 2H), 2.40
(s, 3H), 2.21 (s, 3H); 13C NMR (100 MHz, acetone-d6): d 149.14, 144.17, 140.55,
133.27, 130.76, 130.00, 127.10, 126.58, 125.53, 118.69, 47.40, 29.91, 20.89, 19.93;
MS m=z 287.
Preparation of 5-Methyl-7-[(2-nitrophenyl)sulfonyl]indoline (16)
The product was extracted with ethyl acetate. The organic phase was dried over
magnesium sulfate, and the solvent was removed in vacuo. The crude product was

1846
B. RASZKA, J. MCKEE, AND M. ZANGER
purified by column chromatography (hexane=ethyl acetate, gradient 0–100% ethyl
acetate). The resulting yield was 5-methyl-7-[(2-nitrophenyl)sulfonyl]indoline 16
(0.10 g, 25% isolated yield), a yellow powder: mp 167–168ꢀC; IR (KBr pellet):
3413.81 cmꢃ1 (NꢃH str.), 1537.29 cmꢃ1 (NO2 asym str.), 1376.37 cmꢃ1 (NO2 sym
str.), 1296.18 cmꢃ1 (SO2 asym str.), 1151.62 cmꢃ1 (SO2 sym str.); 1H (400 MHz,
acetone-d6): d 8.30 (d, J ¼ 7.9, 1H), 7.90 (m, J ¼ 8.2, 2H), 7.52 (d, J ¼ 7.6, 1H),
7.19 (s, 1H), 7.14 (s, 1H), 5.88 (s, 1H), 3.72 (t, J ¼ 8.5, 2H), 3.03 (t, J ¼ 8.6, 2H),
2.23 (s, 3H); 13C NMR (100 MHz, acetone-d6): d 135.09, 133.63, 132.60, 131.63,
130.97, 128.58, 128.23, 127.05, 126.19, 124.87, 47.48, 29.89, 19.93; MS m=z 318.
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