SN H reactions of 3-fluoronitroarenes with chloromethyl sulfone as the method for the construction of 6-fluoro-3- sulfonylindoles

Article abstract of DOI:10.1007/s11172-007-0320-9

5-R-6-Fluoro-3-phenylsulfonylindoles were synthesized by the S_N ^H reaction of 3-fluoronitrobenzenes with chloromethyl phenyl sulfone in DMSO in the presence of KOH with subsequent reduction of the nitro group and intramolecular cycli

Full text of DOI:10.1007/s11172-007-0320-9

Russian Chemical Bulletin, International Edition, Vol. 56, No. 10, pp. 2048—2053, October, 2007
2048
SNH reactions of 3ꢀfluoronitroarenes with chloromethyl sulfone
as the method for the construction of 6ꢀfluoroꢀ3ꢀsulfonylindoles
G. A. Zhumabaeva,a S. K. Kotovskaya,aꢀ N. M. Perova,a V. N. Charushin,a,b and O. N. Chupakhina,b
aUrals State Technical University — UPI,
19 ul. Mira, 620002 Ekaterinburg, Russian Federation.
Fax: +7 (343) 374 0458. Eꢀmail: kotovskaya@mail.ustu.ru
bI. Ya. Postovskii Institute of Organic Synthesis, Ural Branch of the Russian Academy of Sciences,
22/20 ul. S. Kovalevskoi/Akademicheskaya, 620041 Ekaterinburg, Russian Federation.
Fax: +7 (343) 374 1189. Eꢀmail: chupakhin@ios.ran.ru
H
5ꢀRꢀ6ꢀFluoroꢀ3ꢀphenylsulfonylindoles were synthesized by the SN reaction of 3ꢀfluoroꢀ
nitrobenzenes with chloromethyl phenyl sulfone in DMSO in the presence of KOH with
subsequent reduction of the nitro group and intramolecular cyclization of imidates.
Key words: vicarious nucleophilic substitution of hydrogen, 3,4ꢀdifluoronitrobenzene,
4ꢀRꢀ3ꢀfluoronitrobenzenes, 5ꢀRꢀ6ꢀfluoroꢀ3ꢀphenylsulfonylindoles.
Nucleophilic substitution of hydrogen in aromatic sysꢀ
fect.6 Ethyl 6ꢀbromoꢀ4ꢀdimethylaminomethylꢀ5ꢀhydrꢀ
oxyꢀ1ꢀmethylꢀ(2ꢀphenylthiomethyl)indoleꢀ3ꢀcarboxylate
hydrochloride (medicine "Arbidol") has an inhibiting efꢀ
fect upon influenza viruses of the А and B types (see
Ref. 7). Sulfonyl derivatives of indole also have various
pharmacological properties. Suffice it to mention that sucꢀ
cinate of [3ꢀ(2ꢀdimethylamino)ethylꢀ1Hꢀindolꢀ5ꢀyl]ꢀNꢀ
methylmethanesulfonamide ("Sumatripan") is used for the
migraine treatment,5 Nꢀarylsulfonylindolecarboxamides
are effective toward the HIVꢀ1 infection,8 whereas
Nꢀarylꢀ and Nꢀalkylindolyl sulfones have antiꢀtumor acꢀ
tivity and are the modulators of 5HT6ꢀreceptors for the
treatment of central nervous system diseases.9—11 Among
the fluoroꢀsubstituted Nꢀsulfonylindoles, compounds
having antiꢀasthmatic and antiꢀallergic properties are
found.12
tems is an efficient method for the functionalization of
arenes and construction of fused heterosystems on their
basis.1 In contrast to the oxidative version of nucleophilic
substitution of hydrogen, proceeding with participation of
external oxidant according to the "addition—oxidation"
scheme SNH(АO), so called "vicarious" nucleophilic subꢀ
stitution2—4 follows the "addition—elimination" scheme
SNH(АE) (Scheme 1). In this case, the role of the oxidant,
which "removes" a pair of electrons from the intermediate
σHꢀadduct, is played by an assisting group А, inserted into
the intermediate, which leaves it as the anion. In case of
nitroarenes, containing good leaving groups (for example,
H
Cl or F), both versions of the SN reactions allow one to
retain the halogen atoms, which opens great potentialities
for further transformations.
Indole ring is a structural fragment of many drugs,
widely used in medicine. Thus, 1ꢀ(pꢀchlorobenzoyl)ꢀ5ꢀ
methoxyꢀ2ꢀmethylindoleꢀ3ꢀacetic acid ("Indometacin")
is an active antiꢀinflammatory medicine,5 alkaloids vinꢀ
blastine and vincristine show antiꢀtumor (cytostatic) efꢀ
Methods for the synthesis of sulfonyl derivatives of
indoles depend on the location of the substituent. Thus,
Nꢀsulfonylindoles are obtained by Nꢀarylsulfonylation of
1Hꢀindoles with arylsulfonyl chlorides,9 5ꢀsulfonylꢀsubꢀ
stituted indoles, by the Fischer cyclization of 4ꢀsulfonylꢀ
Scheme 1
W: electronꢀwithdrawing group (NO2, NO), A: assisting nucleophilic group (Cl, CN, OAr, SAr, etc.),
R: electronꢀwithdrawing group (SO2Ph, SPh, CN, etc.)
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 10, pp. 1980—1984, October, 2007.
1066ꢀ5285/07/5610ꢀ2048 © 2007 Springer Science+Business Media, Inc.

Fluorinated 3ꢀsulfonylindoles
Russ.Chem.Bull., Int.Ed., Vol. 56, No. 10, October, 2007
2049
phenylhydrazines.5 3ꢀSulfonylꢀ1Hꢀindoleꢀ2ꢀcarboxamiꢀ
des were synthesized by the oxidation of 3ꢀarylthioꢀ1Hꢀ
indoleꢀ2ꢀcarboxamides with 3ꢀchloroperbenzoic acid.8
The synthesis of 3ꢀsulfonylꢀsubstituted indoles by the
cyclization of oꢀsubstituted arylsulfonylmethylnitroꢀ
benzenes, obtained by the substitution of hydrogen in
nitro derivatives of arenes upon treatment with vicarious
nucleophiles, viz., aryl chloromethyl sulfones,13,14 is the
most promising method. In the literature, there is no data
on methods for the synthesis of fluoroꢀcontaining 3ꢀsulꢀ
fonylindoles.
Scheme 2
Earlier, we showed that nucleophilic substitution of
hydrogen (SNH) in nitroarenes can be used for the syntheꢀ
sis of fluoroꢀcontaining 1,2,4ꢀbenzotriazines.15 In the
H
present work, a possibility of application of the SN
methodology in nitroarenes as the key step in the syntheꢀ
sis of fluoroꢀcontaining 3ꢀsulfonylindoles was studied.
3,4ꢀDifluoronitrobenzene (1а) and 4ꢀRꢀ3ꢀfluoronitroꢀ
benzenes 1b—f were chosen as the subjects for the
study (Scheme 2). 3,4ꢀDifluoronitrobenzene (1а) was obꢀ
tained by the nitration of oꢀdifluorobenzene,16 whereas
4ꢀRꢀ3ꢀfluoronitrobenzenes 1b—f, by the reaction of 1а
with the corresponding alcohols or morpholine.15
R = F (a), MeO (b), EtO (c), PrnO (d), PriO (e),
(f)
Reagents and conditions: i. ClCH2SO2Ph, KOH/DMSO; ii. Sn,
MeOH, HCl; iii. HC(OEt)3/H+; iv. NaOH/DMSO.
Table 1. Reaction conditions, yields, melting points, elemental analysis and 1H NMR spectroscopy (DMSOꢀd6) data of 4ꢀsubstituted
3ꢀfluoroꢀ6ꢀ(phenylsulfonylmethyl)nitrobenzenes 2b—f
Comꢀ T/°C Yield
pound (τ/h) (%)
M.p.
/°C
(Rf)
Found
Calculated
Molecular
formula
(М)
1H NMR spectrum
(%)
N
δ (J/Hz)
C
H
2b
2c
25
(24)
64
71
184—185
(0.34)*
51.65 3.41 4.41
51.68 3.71 4.30
C14H12FNO5S
(325.33)
3.80 (s, 3 H, MeO); 5.10 (s, 2 H, CH2); 7.07
(d, 1 H, H(5), JH,F = 8.6); 7.63—7.59 (t, 2 H,
Ph); 7.65—7.70 (m, 3 H, Ph); 7.78 (d, 1 H, H(2),
3JH,F = 10.1)
1.39 (t, 3 H, MeCH2O); 4.07 (q, 2 H, МеCH2O);
5.10 (s, 2 H, CH2); 7.09 (d, 1 H, H(5),
4JH,F = 8.2); 7.53—7.59 (t, 2 H, Ph);
7.65—7.73 (m, 3 H, Ph); 7.87 (d, 1 H, H(2),
3JH,F = 11.1)
4
25
(24)
132—133
(0.50)*
53.04 4.05 4.11
53.09 4.15 4.13
C15H14FNO5S
(339.35)
2d
2e
2f
25
(7)
64
60
70
151—152
(0.60)*
54.05 4.31 3.83
54.39 4.56 3.96
C16H16FNO5S
(353.31)
1.02 (t, 3 H, Me(CH2)2O); 1.78, 3.94 (both m,
2 H each, Ме(CH2)2O); 5.10 (s, 2 H, CH2); 7.08
(d, 1 H, H(5), JH,F = 8.3); 7.54—7.60 (t, 2 H,
Ph); 7.66—7.70 (m, 3 H, Ph); 7.88 (d, 1 H, H(2),
3JH,F = 11.1)
4
25
(24)
106—107
(0.62)*
54.43 4.42 3.89
54.39 4.56 3.96
C16H16FNO5S
(353.31)
1.28, 1.31 (both s, 3 H each, Ме2CHО); 4.58
(m, 1 H, Ме2CHО); 5.10 (s, 2 H, CH2); 7.11
4
(d, 1 H, H(5), JH,F = 8.2); 7.52—7.58 (t, 2 H,
Ph); 7.64—7.71 (m, 3 H, Ph); 7.8 (d, 1 H, H(2),
3JH,F = 11.3)
3.11 (m, 4 H, N(CH2)2); 3.72 (m, 4 H, O(CH2)2);
5.09 (s, 2 H, CH2); 6.76 (d, 1 H, H(5),
4JH,F = 8.8); 7.54—7.60 (t, 2 H, Ph); 7.64—7.71
(m, 3 H, Ph); 7.8 (d, 1 H, H(2), 3JH,F = 13.4)
25
(3)
171—172
(0.88)**
50.54 4.09 6.69 C17H17FN2O5S
50.60 4.24 6.90 (380.39)
* Eluent: dichloromethane.
** Eluent: ethyl acetate.

2050
Russ.Chem.Bull., Int.Ed., Vol. 56, No. 10, October, 2007
Zhumabaeva et al.
It was found that the reaction of 4ꢀRꢀ3ꢀfluoroꢀ
nitrobenzenes 1b—f with chloromethyl phenyl sulfone,
proceeding in DMSO in the presence of KOH at room
temperature, leads to the selective substitution of the H(6)
hydrogen atom in oꢀposition to nitro group and is finished
by the formation of 4ꢀRꢀ3ꢀfluoroꢀ6ꢀ(phenylsulfonylꢀ
methyl)nitrobenzenes 2b—f in 60—71% yield (Table 1).
The similar reaction of 3,4ꢀdifluoronitrobenzene (1а) with
chloromethyl phenyl sulfone is complicated by the hydroꢀ
lysis of the C—F bond in pꢀposition to the nitro group and
the product of vicarious substitution of hydrogen was not
isolated in this case. The structures of the synthesized
compounds 2b—f were established on the basis of 1H NMR
spectra, elemental analysis data, and mass spectra. The
assignments of signals of fluorine atoms in the products
of the nitro group in compounds 2b—f was performed by
metal tin in methanol with hydrochloric acid for 3—7 h,
resulting in the corresponding aminoꢀsubstituted sulfones
3b—f in 59—71% yield (Table 2). Amines 3b—f were conꢀ
verted to the corresponding imidates 4b—f in 54—85%
yield by the reflux in triethyl orthoformate in the presence
of catalytic amount of acetic acid (Table 3). In the
1H NMR spectra of imidates 4b—f, the singlet signals
of the methyne protons are observed in the region
7.1—7.3 ppm. The baseꢀcatalyzed intramolecular cyclizaꢀ
tion of imidates 4b—f proceeds under mild conditions at
room temperature for 3—4 h to form fluoroꢀcontaining
3ꢀsulfonylindoles 5b—f in 70—80% yield (Table 4). In the
1H NMR spectra of compounds 5b—f, signals of
the H(4) protons (δ 7.30—7.32) and H(7) protons
(δ 7.21—7.25) as the doublets with constant values on the
n
formed were made by the analysis of the JH,F spinꢀspin
coupling constant values. In the 1H NMR spectra of comꢀ
pounds 2b—f, signals of the H(5) protons in the region
δ 7.0—7.8 and H(2) protons in the region δ 7.8—7.9 as
characteristic doublets with constant values on the fluoꢀ
fluorine atoms JH(4),F(6) = 7.5—8.3 Hz and JH(7),F(6) =
4
3
10.8—12.3 Hz were observed (see Table 4). Signals of
the H(2) methyne protons of the indole ring are in the
region 7.48—7.55 ppm, whereas signals of the NH proꢀ
tons resonate as the broad singlet in the region
11.99—12.65 ppm.
4
3
rine atoms JH(5),F(3) = 8.2—8.8 Hz and JH(2),F(3)
=
10.1—11.4 Hz were observed (see Table 1). The reduction
Table 2. Reaction conditions, yields, melting points, elemental analysis and 1H NMR spectroscopy (DMSOꢀd6) data of 4ꢀsubstituted
3ꢀfluoroꢀ6ꢀ(phenylsulfonylmethyl)anilines 3b—f
Comꢀ T/°C Yield
pound (τ/h) (%)
M.p.
/°C
(Rf)*
Found
Calculated
Molecular
formula
(М)
1H NMR spectrum
(%)
N
δ (J/Hz)
C
H
3b
3c
60—62 71
256—257
56.86 4.63 4.69
56.93 4.77 4.74
C14H14FNO3S
(295.34)
3.52 (s, 3 H, МеO); 4.42 (s, 2 H, CH2);
4.79 (br.s, 2 H, NH2); 6.40 (d, 1 H, H(5),
4JH,F = 9.4); 6.50 (d, 1 H, H(2), 3JH,F = 13.6);
7.54—7.60 (t, 2 H, Ph); 7.66—7.79 (m, 3 H, Ph)
1.22 (t, 3 H, МеCH2O); 3.71 (q, 2 H, МеCH2O);
4.38 (s, 2 H, CH2); 4.76 (br.s, 2 H, NH2); 6.40
(d, 1 H, H(5), 4JH,F = 9.0); 6.47 (d, 1 H, H(2),
3JH,F = 13.4); 7.52—7.58 (t, 2 H, Ph); 7.64—7.78
(m, 3 H, Ph)
60—62 59
(3)
115—116
(0.28)
58.19 5.17 4.42
58.23 5.21 4.52
C15H16FNO3S
(309.37)
3d
60—62 66
(3)
84—85
(0.60)
59.27 5.64 4.17
59.42 5.60 4.33
C16H18FNO3S
(323.39)
0.96 (t, 3 H, МеCH2CH2O); 1.62 (q, 2 H,
МеCH2CH2O); 3.60 (t, МеCH2CH2O); 3.64
(br.s, 2 H, NH2); 4.38 (s, 2 H, CH2); 6.38
(d, 1 H, H(5), 4JH,F = 9.1); 6.48 (d, 1 H, H(2),
3JH,F = 13.1); 7.52—7.58 (t, 2 H, Ph); 7.64—7.78
(m, 3 H, Ph)
3e
3f
60—62 63
(3)
126—127
(0.62)
59.30 5.52 4.21
59.42 5.60 4.33
C16H18FNO3S
(323.39)
1.07, 1.13 (both s, 3 H each, Ме2CHO); 3.99
(m, 1 H, Ме2CHO); 4.39 (s, 2 H, CH2);
4.80 (br.s, 2 H, NH2); 6.40 (d, 1 H, H(5),
4JH,F = 9.4), 6.46 (d, 1 H, H(2), 3JH,F = 13.2);
7.50—7.51 (t, 2 H, Ph); 7.53—7.78 (m, 3 H, Ph)
2.62 (m, 4 H, N(CH2)2); 3.63 (m, 4 H, O(CH2)2);
4.34 (br.s, 2 H, NH2); 4.36 (s, 2 H, CH2); 6.22
(d, 1 H, H(5), 4JH,F = 9.4); 6.44 (d, 1 H, H(2),
3JH,F = 14.4); 7.50—7.56 (t, 2 H, Ph); 7.63—7.74
(m, 3 H, Ph)
60—62 59
(7)
185—186
(0.77)
58.27 5.46 7.09 C17H19FN2O3S
58.38 5.30 7.03 (350.41)
* Eluent: ethyl acetate.

Fluorinated 3ꢀsulfonylindoles
Russ.Chem.Bull., Int.Ed., Vol. 56, No. 10, October, 2007
2051
Table 3. Reaction conditions, yields, melting points, elemental analysis and 1H NMR spectroscopy (DMSOꢀd6) data of 4ꢀsubstituted
Nꢀethoxymethyleneꢀ3ꢀfluoroꢀ6ꢀ(phenylsulfonylmethyl)anilines 4b—f
Comꢀ T/°C Yield
pound (τ/h) (%)
M.p.
/°C
(Rf)*
Found
Calculated
Molecular
formula
(М)
1H NMR spectrum
(%)
δ (J/Hz)
C
H
N
4b
4c
145—146 53
(7)
96—98
(0.80)
56.86 4.63 4.69
56.93 4.77 4.74
C17H18FNO4S
(351.14)
1.29 (t, 3 H, МеCH2O); 4.08 (q, 2 H, МеCH2О);
3.79 (s, МеО); 4.50 (s, 2H, CH2); 6.69 (d, 1 H,
H(2), JH,F = 12.4); 6.97 (d, 1 H, H(5),
4JH,F = 8.9); 7.24 (s, 1 H, CH); 7.45—7.55
(t, 2 H, Ph); 7.61—7.64 (m, 3 H, Ph)
1.28 (t, 3 H, МеCH2O); 4.01 (q, 2 H, МеCH2O);
1.39 (t, 3 H, МеCH2O); 4.06 (q, 2 H, МеCH2O);
4.47 (s, 2 H, CH2); 6.64 (d, 1 H, H(2),
3JH,F =12.3); 6.97 (d, 1 H, H(5), 4JH,F = 9.3);
7.19 (s, 1 H, CH); 7.43—7.51 (t, 2 H, Ph);
7.59—7.65 (m, 3 H, Ph)
3
145—146 85
(3)
132—133
(0.70)
59.08 5.54 3.78
59.16 5.51 3.83
C18H20FNO4S
(365.43)
4d
145—146 65
(7)
68—69
(0.86)
59.82 5.72 3.63
60.14 5.84 3.69
C19H22FNO4S
(379.45)
1.04 (t, 3 H, МеCH2CH2O); 1.79 (m, 2 H,
МеCH2CH2O); 3.91 (t, 3 H, МеCH2CH2О); 1.29
(t, 3 H, МеCH2O); 4.07 (q, 2 H, МеCH2О); 4.49
(s, 2 H, CH2); 6.66 (d, 1 H, H(2), 3JH,F = 11.9);
6.97 (d, 1 H, H(5), 4JH,F = 8.9); 7.22 (s, 1 H,
CH); 7.48—7.52 (t, 2 H, Ph); 7.55—7.63
(m, 3 H, Ph)
4e
4f
145—146 63
(7)
104—105
(0.39)
60.28 5.63 3.85
60.14 5.84 3.69
C19H22FNO4S
(379.45)
1.25, 1.29 (both t, 3 H each, Ме2CHO); 4.43
(m, 1 H, Ме2CHO); 1.31 (t, 3 H, МеCH2O); 4.05
(q, 2 H, МеCH2О); 4.49 (s, 2 H, CH2); 6.65
(d, 1 H, H(2), JH,F = 12.2), 7.01 (d, 1 H, H(5),
4JH,F = 8.8); 7.24 (s, 1 H, CH); 7.44—7.54
(t, 2 H, Ph); 7.60—7.63 (m, 3 H, Ph)
1.29 (t, 3 H, МеCH2O); 4.09 (q, 2 H, МеCH2O);
2.91 (m, 4 H, N(CH2)2); 3.73 (m, 4 H, O(CH2)2);
4.46 (s, 2 H, CH2); 6.60 (d, 1 H, H(2),
3JH,F =13.2); 6.80 (d, 1 H, H(5),4JH,F = 9.2); 7.26
(s, 1 H, CH); 7.43—7.49 (t, 2 H, Ph); 7.51—7.63
(m, 3 H, Ph)
3
145—146 54
(7)
132—133
(0.39)
58.27 5.46 7.99 C20H23FN2O4S
58.38 5.30 7.03 (406.47)
* Eluent: ethyl acetate—dichloromethane (1 : 8).
Characteristics of the compounds synthesized are given in
Tables 1—4.
In conclusion, in the present work, the reactions of
nucleophilic substitution of hydrogen by vicarious reagent,
chloromethyl phenyl sulfone, in the series of fluoroꢀconꢀ
taining nitroarenes, as well as the synthesis of earlier
unknown fluoroꢀcontaining 3ꢀphenylsulfonylindoles were
accomplished for the first time.
Synthesis of 4ꢀRꢀ3ꢀfluoroꢀ6ꢀ(phenylsulfonylmethyl)nitroꢀ
benzenes 2b—f (general procedure). Potassium hydroxide
(9.4 mmol) was added to a stirred solution of 4ꢀRꢀ3ꢀfluoroꢀ
nitrobenzene 1b—f (1.32 mmol) and chloromethyl phenyl sulꢀ
fone (1.32 mmol) in DMSO (5 mL). The reaction mixture was
stirred at room temperature for 3—24 h, then, acidified with
10% aqueous HCl to pH 3—4. The precipitate formed was filꢀ
tered off and recrystallized from ethanol.
Experimental
Synthesis of 4ꢀsubstituted 3ꢀfluoroꢀ6ꢀ(phenylsulfonylꢀ
methyl)anilines 3b—f (general procedure). Tin (4.2 mmol) was
added to a suspension of 4ꢀsubstituted 3ꢀfluoroꢀ6ꢀ(phenylꢀ
sulfonylmethyl)nitrobenzene 2b—f (0.84 mmol) in methanol
(3 mL) and concentrated hydrochloric acid (3 mL). The reacꢀ
tion mixture was refluxed for 3—7 h, then, made basic with
10% aq. NaOH to pH 8—9. The precipitate formed was filtered
off and recrystallized from ethanol.
1
H NMR spectra were recorded on a Bruker WPꢀ250 and
Bruker DRXꢀ400 spectrometers (250.13 and 400.13 MHz),
Me4Si was used as the internal standard. Mass spectra were
recorded on a Varian MATꢀ311A instrument, conditions of the
recording: accelerating voltage, 3 kV; energy of the ionizing
ions, 70 eV; direct inlet of a sample into the source of electrons.
Reaction course and purity of the compounds synthesized were
monitored by TLC on Silufol UVꢀ254 plates in dichloromethane,
ethyl acetate, and in ethyl acetate—dichloromethane (1 : 8).
Synthesis of 4ꢀsubstituted Nꢀethoxymethyleneꢀ3ꢀfluoroꢀ6ꢀ
(phenylsulfonylmethyl)anilines 4b—f (general procedure). Acetic

2052
Russ.Chem.Bull., Int.Ed., Vol. 56, No. 10, October, 2007
Zhumabaeva et al.
Table 4. Reaction conditions, yields, melting points, elemental analysis, mass and 1H NMR spectroscopy (DMSOꢀd6) data of
5ꢀsubstituted 6ꢀfluoroꢀ3ꢀphenylsulfonylindoles 5b—f
Comꢀ T/°C Yield M.p./°C
pound (τ/h) (%) (Rf)*
Found
Calculated
Molecular
formula
(М)
MS
m/z (Irel (%))
1H NMR spectrum
(%)
N
δ (J/Hz)
C
H
5b
25
(3)
41
134—135 58.80 3.97 4.59 C15H12FNO3S 305 [M]+ (100),
3.91 (s, 3 H, МеO); 7.25 (d, 1 H,
H(7), 3JH,F = 11.5); 7.33 (d, 1 H,
H(4), 4JH,F = 8.2); 7.51 (s, 1 H,
CH); (7.54—7.55 (t, 2 H, Ph);
7.94—7.97 (m, 3 H, Ph); 12.02
(br.s, 1 H, NH)
1.43 (t, 3 H, МеCH2O); 4.11
(q, 2 H, МеCH2O); 7.22 (d, 1 H,
H(7), 3JH,F = 10.8); 7.30 (d, 1 H,
H(4), 4JH,F = 8.1); 7.48 (s, 1 H,
CH); 7.49—7.51 (m, 2 H, Ph);
7.91—7.94 (m, 3 H, Ph); 12.65
(br.s, 1 H, NH)
(0.58)
59.03 3.96 4.59
(305.17)
290 [M]+ (1.76),
228 [M]+ (1.89),
164 [M]+ (13.26)
5c
25
(3)
82
256—257 58.67 4.28 4.29 C16H14FNO3S 319 [M]+ (100),
(0.58)
60.18 4.42 4.38
(319.29)
290 [M]+ (5.94),
242 [M]+ (2.13),
178 [M]+ (4.59)
5d
5e
5f
25
(5)
50
52
75
214—215 61.53 5.03 4.34 C17H16FNO3S 333 [M]+ (41.6),
1.09 (t, 3 H, МеCH2CH2O); 1.83,
(0.52)
61.25 4.83 4.20
(333.39)
291 [M + 1]+ (100), 4.03 (both t, 2 H each, Ме
214 [M]+ (5.80),
150 [M]+ (27.01)
(CH2)2O); 7.24 (d, 1 H, H(7),
3JH,F = 10.8); 7.31 (d, 1 H, H(4),
4JH,F = 8.2); 7.52 (s, 1 H, CH);
7.54 (t, 2 H, Ph); 7.93—7.97 (m,
3 H, Ph); 12.65 (br.s, 1 H, NH)
1.24, 1.34 (both t, 3 H each,
Ме2CHO); 4.54 (m, 1 H,
Ме2CHO); 7.23 (d, 1 H, H(7),
3JH,F = 11.1), 7.31 (d, 1 H, H(4),
4JH,F = 7.5); 7.49 (s, 1 H, CH);
7.53—7.55 (t, 2 H, Ph);
25
(3.5)
156—157 59.99 4.88 3.98 C17H16FNO3S 333 [M]+(16.41),
(0.70)
61.25 4.83 4.20
(333.39)
291 [M]+ (100),
214 [M]+ (4.73),
150 [M]+ (19.96)
7.93—7.97 (m, 3 H, Ph)
3.01 (m, 4 H, N(CH2)2); 3.76
25
(4)
275
(0.21)
60.06 4.47 7.46 C18H17FN2O3S 360 [M]+ (89.45),
59.98 4.75 7.77 (360.40)
345 [M + 1]+ (1.29), (m, 4 H, O(CH2)2); 7.20 (d, 1 H,
219 [M]+ (3.31)
H(7), 3JH,F = 12.3); 7.32 (d, 1 H,
H(4), 4JH,F = 8.3); 7.55 (s, 1 H,
CH); 7.56—7.60 (m, 2 H, Ph);
7.94—7.96 (m, 3 H, Ph); 11.99
(br.s, 1 H, NH)
* Eluent: ethyl acetate—dichloromethane (1 : 8).
acid (few drops) was added to a solution of 4ꢀsubstituted
3ꢀfluoroꢀ6ꢀ(phenylsulfonylmethyl)aniline 3b—f (0.3 mmol) in
triethyl orthoformate (4 mL). The reaction mixture was refluxed
for 7 h and cooled, hexane (5 mL) was added, the precipitate
formed was filtered off and recrystallized from hexane—ethyl
acetate (3 : 1).
33112а), by the Russian Federation President Council for
Grants (Program for the State Support of Leading Scienꢀ
tific Schools of the RF, Grant NShꢀ9178.2006.3), and
National Civilian Research and Development Foundaꢀ
tion (Grant BP2M05).
Synthesis of 5ꢀsubstituted 6ꢀfluoroꢀ3ꢀphenylsulfonylindoles
5b—f (general procedure). Finely powdered NaOH (0.08 g,
2 mmol) was added to a solution of 4ꢀsubstituted Nꢀethoxyꢀ
methyleneꢀ3ꢀfluoroꢀ6ꢀ(phenylsulfonylmethyl)aniline 4b—f
(0.4 mmol) in DMSO (4 mL). The reaction mixture was stirred
at room temperature for 3—4 h, then, neutralized with 10%
aq. NH4Cl. The precipitate was filtered off and recrystallized
from ethanol—ethyl acetate (2 : 1).
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This work was financially supported by the Russian
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Received February 16, 2007;
in revised form July 10, 2007