Reaction of N-methylsulfonyl-and N-(p-tolylsulfonyl)-2-(cyclopent-1-en-1- yl)anilines with bromine in the presence of potassium thiocyanate and in methanol

Article abstract of DOI:10.1134/S1070363208030183

The reactions of N-methylsulfonyl-and N-(p-tolylsulfonyl)-2-(cyclopent-1- en-1-yl)-6-methylaniline with molecular bromine in the presence of potassium thiocyanate gave N-methylsulfonyl-and N-(ptolylsulfonyl)-2-(5- isothiocyanatocyclopent-1-en-1-yl)-6-methylanilines. N-Methylsulfonyl-2- (cyclopent-1-en-1-yl)-6-methylaniline reacted with bromine in methanol in the presence of NaHCO₃ or with CuBr₂ in MeOH to afford N-methylsulfonyl-2-(5-methoxycyclopent-1-en-1-yl)-6-methylaniline. The reaction of N-methylsulfonyl-2-(5-isothiocyanatocyclopent-1-en-1-yl)-6-methylaniline with diethylamine led to the formation of N-methylsulfonyl-2-{5- [diethylamino(thioxo)methyl]aminocyclopent-1-en-1-yl}-6-methylaniline which was converted into 5-methyl-4-methylsulfonyl-2,3,3a,4-tetrahydrocyclopenta[b]indole by heating with potassium hydroxide.

Full text of DOI:10.1134/S1070363208030183

ISSN 1070-3632, Russian Journal of General Chemistry, 2008, Vol. 78, No. 3, pp. 442–445. © Pleiades Publishing, Ltd., 2008.
Original Russian Text © R.R. Gataullin, A.A. Fatykhov, 2008, published in Zhurnal Obshchei Khimii, 2008, Vol. 78, No. 3, pp. 457–460.
Reaction of N-Methylsulfonyl- and N-(p-Tolylsulfonyl)-
2-(Cyclopent-1-en-1-yl)anilines with Bromine in the Presence
of Potassium Thiocyanate and in Methanol
R. R. Gataullin and A. A. Fatykhov
Institute of Organic Chemistry, Ufa Research Center, Russian Academy of Sciences,
pr. Oktyabrya 71, Ufa, 450054 Bashkortostan, Russia
e-mail: chemorg@anrb.ru
Received August 31, 2007
Abstract—The reactions of N-methylsulfonyl- and N-(p-tolylsulfonyl)-2-(cyclopent-1-en-1-yl)-6-methyl-
aniline with molecular bromine in the presence of potassium thiocyanate gave N-methylsulfonyl- and N-(p-
tolylsulfonyl)-2-(5-isothiocyanatocyclopent-1-en-1-yl)-6-methylanilines. N-Methylsulfonyl-2-(cyclopent-1-en-
1-yl)-6-methylaniline reacted with bromine in methanol in the presence of NaHCO3 or with CuBr2 in MeOH to
afford N-methylsulfonyl-2-(5-methoxycyclopent-1-en-1-yl)-6-methylaniline. The reaction of N-methyl-
sulfonyl-2-(5-isothiocyanatocyclopent-1-en-1-yl)-6-methylaniline with diethylamine led to the formation of N-
methylsulfonyl-2-{5-[diethylamino(thioxo)methyl]aminocyclopent-1-en-1-yl}-6-methylaniline which was
converted into 5-methyl-4-methylsulfonyl-2,3,3a,4-tetrahydrocyclopenta[b]indole by heating with potassium
hydroxide.
DOI: 10.1134/S1070363208030183
Derivatives of ortho-cycloalkenylanilines are used
in the synthesis of biologically active compounds [1]
and catalysts for olefin polymerization [2]. Some of
these compounds exhibit local anesthetic effect [3].
Therefore, they attract interest of many researchers. In
continuation of our studies on ortho-cycloal-
kenylanilines in the present work we examined
reactions of N-methylsulfonyl- and N-(p-tolyl-
sulfonyl)-2-(cyclopent-1-en-1-yl)-6-methylanilines Ia
and Ib [4] with molecular bromine in the presence of
potassium thiocyanate and in methanol.
in acetonitrile or methylene chloride are accompanied
by instantaneous disappearance of brown color, and
the products are unsaturated ketones IIIa and IIIb
(Scheme 1), which are likely to be formed via
intermediate B. The presence of moisture in the
reaction mixture promotes replacement of the labile
bromine atom by hydroxy group, yielding allylic
alcohol C, and oxidation of the latter gives ketone IIIa
or IIIb [6]. The latter is also formed when the reaction
is carried out under argon.
In the reaction of anilide Ia with bromine in
methanol in the presence of NaHCO3 at room
temperature methyl ether IV is formed in high yield.
Obviously, in this case the bromine atom in the allylic
position is replaced ny methoxy group. Ether IV was
also obtained when compound Ia in methanol was
stirred in the presence of copper(II) bromide. The
mechanisms of olefin transformation by the action of
copper(II) bromide have been studied in sufficient
detail for cyclopentadiene [7]. Taking into account
published data on the behavior of stable allylic
bromide (which is structurally related to bromide B)
derived from cyclohexenylaniline [4] in methanol in
The reactions of sulfonamides Ia and Ib with
molecular bromine in acetonitrile in the presence of
potassium thiocyanate gave compounds IIa and IIb,
respectively, in high yields. Presumably, in the first
step unstable vicinal dibromide A is formed via trans-
addition of bromine at the double bond in the
cyclopentene ring. Elimination of hydrogen bromide
from intermediate A gives allylic bromide B. This
reaction scheme is supported by the following. As we
showed previously [4, 5], the reactions of
cyclopentenylanilines Ia and Ib with 2 equiv of
bromine in the presence of sodium hydrogen carbonate
442

REACTION OF N-METHYLSULFONYL-
443
Scheme 1.
R = Me (a), 4-MeC6H4 (b).
the presence of CuBr2, we presumed that the reaction
involves intermediate formation of complex G which
loses [Cu2Br3]– species and a proton (Scheme 2).
but they seem to be less probable as applied to the
reaction under study.
The condensation of isothiocyanate IIa with
diethylamine occurs at the carbon atom of the NCS
group with formation of compound V (Scheme 1). The
reaction of IIa with potassium hydroxide in boiling
acetonitrile is accompanied by elimination of the NCS
group and cyclization to indole VI having unsaturated
C8b=C1 bond.
The reaction of sulfonamides Ia and Ib with
bromine in the presence of potassium thiocyanate is
likely to involve replacement of the bromine atom in
intermediate B by thiocyanato group with formation of
thiocyanate D, and its subsequent allylic isomerization
gives isothiocyanate IIa or IIb. Also, alternative
mechanisms proposed in [8–10] cannot be ruled out,
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 78 No. 3 2008

444
GATAULLIN, FATYKHOV
Scheme 2.
1
The structure of the isolated products was
Rf 0.4 (C6H6–EtOAc, 85:15). H NMR spectrum,
(CDCl3), δ, ppm: 1.90 s (3H, CH3), 1.91–2.43 m (4H,
CH2), 3.02 s (3H, CH3), 5.36 d.t (1H, 5′-H, J1 = 2.5, J2 =
7.5 Hz), 6.09 q (1H, 2′-H, J = 2.0 Hz), 6.28 br.s (1H,
determined on the basis of analytical and spectral data.
13
The C NMR spectra (JMOD) of compounds IIa and
IIb contained doublet signals at δC ~64 and ~131 ppm
from the C5′ atom and carbon atom in the N=C=S
group. Compound V displayed in the 13C NMR
spectrum signals in the aliphatic region due to two
methyl and two methylene groups and a signal at δC
178.5 ppm which is typical of thiourea fragment. The
mass spectrum of V contained the molecular ion peak
with m/z 381. Compound VI characteristically showed
in the 13C NMR spectrum (JMOD) a doublet at δC 74.8
from the bridgehead C3a atom. The molecular ion peak
with m/z 249 was present in the mass spectrum of VI.
NH), 7.13 d (1H, Harom, J = 8.0 Hz), 7.25 t (1H, Harom
,
13
J = 8.0 Hz), 7.51 d (1H, Harom, J = 8.0 Hz). C NMR
spectrum (CDCl3), δC, ppm: 19.0 (CH3), 30.6 (C3′),
32.4 (C4′), 41.4 (CH3), 63.8 (C5′), 127.9 (C4), 128.3
(C2′), 130.9 (C3), 131.5 (C6), 131.9 (NCS), 134.6 (C2),
134.7 (C5), 137.3 (C1), 140.8 (C1′). Found, %: C 54.35;
H 5.08; N 8.91; S 20.58. C14H16N2O2S2. Calculated, %:
C 54.52; H 5.23; N 9.08; S 20.79.
N-[2-(5-Isothiocyanatocyclopent-1-en-1-yl)-6-
methylphenyl]-4-toluenesulfonamide (IIb) was
synthesized in a similar way from 0.327 g of
sulfonamide Ib. Yield 0.37 g (97%). 1H NMR
spectrum (CDCl3), δ, ppm: 1.92 s (3H, CH3), 1.95–
2.39 m (4H, CH2), 2.42 s (3H, CH3), 5.32 d.t (1H, 5′-
H, J1 = 2.0, J2 = 7.6 Hz), 6.04 q (1H, 2′-H, J = 4.0 Hz),
6.19 br.s (1H, NH), 7.11 d (1H, Harom, J = 8.0 Hz), 7.23
t (1H, Harom, J = 8.0 Hz), 7.37 d (2H, Harom, J = 8.3
EXPERIMENTAL
1
13
The H and C NMR spectra were recorded from
solutions in CDCl3 on a Bruker AM 300 instrument
operating at 300.13 and 75.45 MHz, respectively. The
chemical shifts were measured relative to
tetramethylsilane as internal reference. The elemental
compositions were determined on an M-185B CHN
Analyzer. Qualitative TLC analysis was performed
using Sorbfil plates (PTSKh-AF-V-UF, Sorbpolimer
Ltd., Stavropol, Russia); spots were detected under UV
light and by treatment with iodine vapor.
Hz), 7.51 d (1H, Harom, J = 8.0 Hz), 7.62 d (2H, Harom
,
J = 8.3 Hz). 13C NMR spectrum (CDCl3), δC, ppm:
18.2, 21.2 (CH3); 30.2 (C3′); 31.9 (C3″); 63.1 (C5′);
126.8, 127.7, 128.3, 129.2, 130.5, 133.8 (C2″, C6″, C3,
C4, C3″, C5″, C5, C2′); 131.1, 134.5, 137.3, 137.5, 140.7,
143.4 (C1, C2, C6, C1″, C4″, C1′, C5′); 131.7 (NCS).
Found, %: C 62.36; H 5.18; N 7.11; S 16.42.
C20H20N2O2S2. Calculated, %: C 62.47; H 5.24; N
7.29; S 16.68.
N-[2-(5-Isothiocyanatocyclopent-1-en-1-yl)-6-
methylphenyl]methanesulfonamide (IIa). A solution
of 0.16 g of molecular bromine in 5 ml of acetonitrile
was slowly added under stirring to a solution of 0.251
g of sulfonamide Ia and 0.97 g of potassium
thiocyanate in 15 ml of acetonitrile. After 12 h, the
mixture was filtered, and the filtrate was evaporated
under reduced pressure. The residue was washed with
water (2×50 ml), the organic phase was separated and
dried over sodium sulfate, and the solvent was
removed under reduced pressure. To remove tarry
impurities, the residue was subjected to
chromatography on a short column charged with 1 g of
silica gel using benzene as eluent. Yield 0.3 g (97%),
N-[2-(5-Methoxycyclopent-1-en-1-yl)-6-
methylphenyl]methanesulfonamide (IV). A solution
of 0.25 g of compound Ia in 5 ml of methanol was
added dropwise under stirring to a solution of 0.45 g of
CuBr2 in 20 ml of methanol. After 12 h, the mixture
was diluted with 25 ml of water and extracted with
methylene chloride (30 ml), the organic phase was
dried over Na2SO4, the solvent was removed under
reduced pressure, and the residue was purified from
tarry impurities by chromatography on a 2×20-cm
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 78 No. 3 2008

REACTION OF N-METHYLSULFONYL-
445
column charged with 0.5 g of silica gel using benzene
as eluent. Yield 0.27 g (96%), viscous material, Rf 0.35
(C6H6–EtOAc, 9:1). IR spectrum: ν 3280 cm–1 (NH).
1H NMR spectrum (CDCl3), δ, ppm: 1.91–2.72 m (4H,
CH2), 2.54 s (3H, CH3), 2.94 s (3H, CH3), 3.41 s (3H,
OCH3), 4.62 m (1H, 5′-H), 5.97 m (1H, 2′-H), 6.93 d
(1H, 3-H, J = 7.2 Hz), 7.08 t (1H, 4-H, J = 7.2 Hz),
7.22 d (1H, 5-H, J = 7.2 Hz), 8.30 s (1H, NH). 13C
NMR spectrum (CDCl3), δC, ppm: 19.5, 40.5, 56.8
(3CH3); 29.8 (C3′), 30.4 (C4′), 90.0 (C5′), 126.7 (C4),
128.0 (C2′), 131.0 (C3), 133.3 (C6), 135.3 (C2), 136.5
(C5), 136.0 (C1′), 142.5 (C1). Found, %: C 59.45; H
6.43; N 4.67; S 11.02. C14H19NO3S. Calculated, %: C
59.76; H 6.81; N 4.98; S 11.39.
residue was dissolved in 30 ml of methylene chloride,
and the solution was washed with water (2×50 ml),
and dried over sodium sulfate. Removal of the solvent
under reduced pressure gave 0.246 g (99%) of the
crude product which was purified by chromatography
on a short column charged with silica gel. Yield 0.2 g
(80%), Rf 0.75 (C6H6–EtOAc, 85:15). 1H NMR
spectrum (CDCl3), δ, ppm: 2.00–2.75 m (4H, 2CH2),
2.53 s (3H, CH3), 2.94 s (3H, CH3), 4.96 d.d.t (1H, 3a-
H, J1 = 2.5, J2 = 3.5, J3 = 6.0 Hz), 5.95 d.t (1H, 1-H, J1 =
2.4, J2 = 3.2 Hz), 7.05 d.t (1H, 7-H, J1 = 6.1, J2 = 6.8 Hz),
7.28 d (1H, 8-H, J = 6.8 Hz), 7.36 d (1H, 6-H, J = 6.1 Hz).
13C NMR spectrum (CDCl3), δC, ppm: 21.5 (CH3),
34.7, 37.1 (2CH2), 37.2 (CH3), 74.8 (C3a), 119.9 (C7),
121.2 (C8), 124.7 (C1), 127.3 (C8a), 127.4 (C5), 133.4
(C6), 142.4 (C8b), 146.4 (C4a). Mass spectrum, m/z: 249
[M]+, 234 [M − CH3]+, 185 [M − SO2Me]+ (base peak).
Found, %: C 62.39; H 5.48; N 5.46; S 12.65.
C13H15NO2S. Calculated, %: C 62.63; H 6.06; N 5.62;
S 12.86.
N-(2-{5-[Diethylamino(thioxo)methylamino]
cyclopent-1-en-1-yl}-6-methylphenyl)methane-
sulfonamide (V). Diethylamine, 5 ml, was added to a
solution of 0.308 g of compound IIa in 5 ml of
chloroform. After 30 min, the mixture was diluted with
100 ml of chloroform and washed with 50 ml of water.
The organic phase was dried over Na2SO4, the solvent
was removed under reduced pressure, 5 ml of ethanol
was added to the residue, and the mixture was heated
for 10 min under reflux. After cooling, the solvent was
separated by decanting from the oily residue, and the
residue was dried under reduced pressure. Yield 0.354
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g (93%), amorphous substance. H NMR spectrum
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1.81–2.55 m (4H, CH2), 2.18 s (3H, CH3), 3.02 s (3H,
CH3), 3.50 q (4H, CH2, J = 7.0 Hz), 5.32 d.d (1H, 5′-H,
J1 = 2.7, J2 = 4.0 Hz), 5.90 s (1H, NH), 6.05 d.t (1H,
2′-H, J1 = 2.4, J2 = 4.6 Hz), 6.82 br.s (1H, NH), 7.11–
7.28 m (3H, Harom). 13C NMR spectrum (DMSO-d6),
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44.2 (2CH2), 42.3 (CH3), 63.3 (C5′), 126.3 (C4), 127.2
(C2′), 129.5 (C3), 132.3 (C5), 132.4 (C6), 136.5 (C2),
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5-Methyl-4-methylsulfonil-2,3,3a,4-tetrahydro-
cyclopenta[b]indole (VI). Compound IIa, 0.308 g,
was dissolved in 10 ml of acetonitrile, 0.28 g of
potassium hydroxide was added to the solution, and
the mixture was heated for 5 min under reflux. The
solvent was evaporated under reduced pressure, the
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 78 No. 3 2008