Reactions of polyfluorinated chalcones with o-aminobenzenethiol and its zinc salt

Article abstract of DOI:10.1007/s11172-011-0058-2

The reactions of polyfluorochalcones with o-aminothiophenol in methanol in the presence of HCl afford polyfluorine-substituted 2,3-dihydrobenzo[b][1,5] thiazepines. In some cases, the cyclization is accompanied by fluorine substitution in the perfluorophenyl ring. Probably, the formation of thiazepines proceeds through the Michael thia-adduct. The Zn salt of o-aminothiophenol reacts with chalcones in DMF exclusively via fluorine substitution.

Full text of DOI:10.1007/s11172-011-0058-2

Russian Chemical Bulletin, International Edition, Vol. 60, No. 2, pp. 361—367, February, 2011
361
Reactions of polyfluorinated chalcones with oꢀaminobenzenethiol
and its zinc salt
K. S. Shmuilovich, N. A. Orlova, I. V. Beregovaya, and V. V. Shelkovnikov
N. N. Vorozhtsov Novosibirsk Institute of Organic Chemistry,
Siberian Division of the Russian Academy of Sciences,
9 prosp. Akad. Lavrent´eva, Novosibirsk, 630090 Russian Federation.
Fax: +7 (383) 330 9752. Eꢀmail: ona@nioch.nsс.ru
The reactions of polyfluorochalcones with oꢀaminothiophenol in methanol in the presence
of HCl afford polyfluorineꢀsubstituted 2,3ꢀdihydrobenzo[b][1,5]thiazepines. In some cases, the
cyclization is accompanied by fluorine substitution in the perfluorophenyl ring. Probably, the
formation of thiazepines proceeds through the Michael thiaꢀadduct. The Zn salt of oꢀaminoꢀ
thiophenol reacts with chalcones in DMF exclusively via fluorine substitution.
Key words: polyfluorinated chalcones, polyfluorinated 2,4ꢀdiarylꢀ2,3ꢀdihydrobenzo[b][1,5]ꢀ
thiazepines, Michael thiaꢀadducts.
Chalcones (benzalacetophenones, 1,3ꢀdiarylpropꢀ2ꢀ
enꢀ1ꢀones) are highly reactive due to the presence of the
carbonyl group conjugated with the double bond, which
provides their interaction with nucleophiles at both the
carbonyl group and double bond: Michael addition.1 Polyꢀ
fluorineꢀsubstituted chalcones have an additional reacꢀ
tion center: the perfluorophenyl ring in which the fluorine
atoms are easily substituted by various nucleophilic groups.2
Reactions of chalcones with binucleophiles leading to
a diverse series of heterocyclic compounds are of special
interest.1 So, the interaction of chalcones with oꢀaminoꢀ
thiophenol serves as a method for synthesis of sevenꢀmemꢀ
bered heterocycles, 1,5ꢀbenzothiazepines, which are widely
used pharmacophores.3—8 In addition, 4ꢀarylꢀsubstituted
thiazepines in which the aryl ring is conjugated with the
azomethine group are structurally similar to 2ꢀphenylꢀ
pyridines and related heterocycles, whose complexes find
use in phosphorescent organic photoemission diodes.9
The reactions of nonꢀfluorinated chalcones and their
derivatives monoꢀ and disubstituted in aromatic rings with
oꢀaminothiophenol were studied3—6,10—15 in detail. The
reaction is believed to proceed as a coupled addition of
the SH group to the double bond of chalcone followed by
the formation of the Michael thiaꢀadduct and the subseꢀ
quent intramolecular cyclization of the latter to benzoꢀ
thiazepine.10,11
The purpose of this work is to study the reactions of
polyfluorinated chalcones 1а—с16 with оꢀaminothiophenol
(2) and its zinc salt (3).
Results and Discussion
We have shown that reflux of polyfluorinated chalꢀ
cones 1а—с with an excess of oꢀaminothiophenol (2) in
methanol in the presence of catalytic amounts of HCl
(cf. Ref. 11) produces polyfluorosubstituted 1,5ꢀbenzoꢀ
thiazepines 4а—с. It should be mentioned that the reacꢀ
tions proceed with some distinctions, depending on the
structure of the starting chalcone. For instance, according
to the 1H and 19F NMR spectral data, when perfluorobenꢀ
zalacetophenone 1а is refluxed with 2 moles of thiophenol
2, the reaction mixture contains approximately equal
amounts of 2ꢀ(perfluorophenyl)ꢀ4ꢀphenylꢀ2,3ꢀdihydroꢀ
benzo[b][1,5]thiazepine (4а) and the product of addition
to the βꢀC atom, 3ꢀ(2ꢀaminophenylthio)ꢀ3ꢀ(perfluoropheꢀ
nyl)ꢀ1ꢀphenylpropanꢀ1ꢀol (5a) (Scheme 1).
The reaction of benzalperfluoroacetophenone 1b with
two moles of compound 2 affords 1,5ꢀbenzothiazepine 4b
substituted to the paraꢀposition of the C6F5 group by the
оꢀaminothiophenol residue (Scheme 2). The higher moꢀ
bility of the fluorine atom compared that in the previous
reaction (see Scheme 1) is related, most likely, to the
withdrawing influence of the azomethine group neighborꢀ
ing to the perfluorophenyl ring. A threefold excess of the
reactant was used in the reaction of decafluorosubstituted
chalcone 1с with thiophenol 2, taking into account that
fluorine can be substituted in the both perfluorophenyl
groups. However, the single product of this reaction is
Ar = Ph, Ar´ = C6F5 (a), Ar = C6F5, Ar´ = Ph (b), Ar = Ar´ = C6F5 (c)
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 2, pp. 353—358, February, 2011.
1066ꢀ5285/11/6002ꢀ361 © 2011 Springer Science+Business Media, Inc.

362
Russ.Chem.Bull., Int.Ed., Vol. 60, No. 2, February, 2011
Shmuilovich et al.
Scheme 1
action of chalcones 1a—с with thiophenol 2 in methanol
at 20 °C for 3—6 h (Scheme 3).
Scheme 3
Ar = Ph, Ar´ = C6F5 (a), Ar = C6F5, Ar´ = Ph (b), Ar = Ar´ = C6F5 (c)
Reagents and conditions: 2, MeOH, 20 °C, 3—6 h.
Reagents and conditions: HCl, MeOH, reflux.
Reflux of synthesized compounds 5a—c in methanol
in the presence of HCl for 3 h gives various mixtures of
products. For instance, compound 5а undergoes partial
ring closure to form benzothiazepine 4а and partially 5а
transforms into chalcone 1а; however, the most part of 5a
remains unchanged under these conditions (Scheme 4).
2ꢀ(perfluorophenyl)ꢀ4ꢀ[2,3,5,6ꢀtetrafluoroꢀ4ꢀ(2ꢀaminoꢀ
phenylthio)phenyl]ꢀ2,3ꢀdihydrobenzo[b][1,5]thiazepine
(4с) (see Scheme 2). Fluorine atom substitution is obꢀ
served in one of the C6F5 groups, namely, in position 4 of
the thiazepine ring, and is due most likely to the aforemenꢀ
tioned reason.
Scheme 4
Scheme 2
Reagents and conditions: HCl, MeOH, reflux.
On reflux under the same conditions, thiaꢀadduct 5b is
completely consumed. The reaction mixture contains chalꢀ
cones 1b and 6b substituted in the fluorinated ring, as well
as benzothiazepines 4b and 4d, the former of which also
contains the oꢀaminothiophenol residue in the paraꢀposiꢀ
tion of the perfluorophenyl ring (Scheme 5).
Under these conditions, compound 5с also forms
a complicated mixture of products containing chalcone
1с, thiaꢀadducts 5с and 5d, and benzothiazepines 4с and
4е, both substituted in the fluorinated ring and unsubstiꢀ
tuted (Scheme 6).
4: Ar = Ph (b), C6F5 (c)
Reagents and conditions: 2, HCl, MeOH, reflux.
To reveal the sequence of steps of formation of benzoꢀ
thiazepines, we synthesized thiaꢀadducts 5a—с by the reꢀ
Scheme 5
Reagents and conditions: HCl, MeOH, reflux.

Reactions of polyfluorinated chalcones
Russ.Chem.Bull., Int.Ed., Vol. 60, No. 2, February, 2011
363
Scheme 6
Reagents and conditions: HCl, MeOH, reflux.
The presence of chalcones 1a—с in the reaction mixꢀ
tures indicates that the addition to the βꢀC atom is reꢀ
versible. It is most likely that the formation of chalcone 6b
and thiazepines 4b,с substituted in the perfluoropheꢀ
nyl rings is the result of interaction of compounds 1b and
4d,е with oꢀaminophenol evolved upon the decomposiꢀ
tion of βꢀadducts 5b,с. Reversibility of the formation
of Michael thiaꢀadducts from nonꢀfluorinated chalꢀ
cones and oꢀaminothiophenol was not observed earlier;
however, it was shown17 that the cyclization of the
thiaꢀadducts to benzothiazepines is reversible and can
also contribute to the complicated composition of reꢀ
action mixtures formed upon cyclization of thiaꢀadꢀ
ducts 5а—с.
The relative differences in total energies determined
with respect to the value of (Etot5е – Etot1е) indicate how the
thermal effect of the reaction 1a—с + H2NC6H4SH → 5a—с
is smaller than that for the reaction 1e + H2NC6H4SH → 5e.
It seems natural to assume that a decrease in the thermal
effect of the direct reaction would favor the occurrence of
the backward reaction. The calculated values of relative
differences of total energies correlate with the content of
products of the backward reactions (chalcones) in the reacꢀ
tion mixtures.
Chalcone 6b and paraꢀsubstituted chalcones 6a and 6c
were synthesized by the reaction of chalcones 1a—c with
oꢀaminothiophenol zinc salt (3) in DMF at room temperꢀ
atures. In all cases, the reaction proceeds only via nucleoꢀ
philic substitution of the fluorine atom in the paraꢀposiꢀ
tion of the perfluorophenyl ring (Scheme 7).
To explain the lower stability of polyfluorineꢀsubstiꢀ
tuted thiaꢀadducts 5а—с compared to that of nonꢀfluoriꢀ
nated compound 5е (see Ref. 17), we performed the PBE/3z
calculations for compounds 1a—с and 5a—с and nonꢀ
fluorinated compounds 1е and 5е (Table 1).
The exclusive formation of paraꢀsubstituted chalcones
6а—с is due to the use of an aprotic polar solvent DMF.
For instance, we showed that in DMF at 20 °C oꢀaminoꢀ
thiophenol (2) with chalcone 1а forms predominantly
paraꢀsubstituted chalcone 6а with a minor admixture of
1
βꢀthiaꢀadduct 5а; according to the data of H and 19F
NMR spectroscopy, the ratio 6a : 5a is 9 : 1.
The structures of the synthesized compounds were deꢀ
1
termined by the IR and Н and 19F NMR spectral data
and confirmed by elemental analysis. The yields, melting
points, and elemental analysis data are presented in Table 2.
The spectral data are given in Table 3.
Table 1. Total energies (Etot) of compounds 1a—c,е and 5a—с,е
and the relative differences of total energies (ΔΔE)* according to
the data of DFT/PBE/3z calculations
Thus, in the present work we studied the reactions of
three polyfluorinated chalcones, viz., perfluorobenzalaceꢀ
tophenone (1а), benzalperfluoroacetophenone (1b), and
decafluorobenzalacetophenone (1c), with оꢀaminothioꢀ
phenol and its zinc salt. It was shown that the reactions of
polyfluorochalcones with oꢀaminothiophenol in methaꢀ
nol in the presence of HCl afforded polyfluoroarylꢀsubstiꢀ
tuted 2,3ꢀdihydrobenzo[b][1,5]thiazepines and, in several
cases, was accompanied by the substitution of the fluorine
atom in the paraꢀposition of the perfluorophenyl ring by
the oꢀaminothiophenol residue. It is most likely that the
first step is the addition of the thiol group of the reactant
Chalcone
–Etot
/a.u.
Thiaꢀ
adduct
–Etot
/a.u.
ΔΔE
1
5
/kcal mol–1
1a
1b
1c
1e
1149.38284
1149.37662
1645.31596
1653.43613
5a
5b
5c
5e
1834.79842
1834.78911
2330.72938
1338.85716
3.42
5.35
4.78
0
* The relative difference of total energies (ΔΔE) were determined
with respect to the difference of total energies of compounds 1e
and 5e (Etot5e – Etot1e).

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Russ.Chem.Bull., Int.Ed., Vol. 60, No. 2, February, 2011
Shmuilovich et al.
Scheme 7
2
Reagents and conditions: DMF, 20 °С.
and the precipitate that formed was filtered off, washed with
water, and dried in air. To isolate thiazepine 4с, the reaction
mixture was evaporated and the oily residue was triturated with
hexane—diethyl ether (1 : 1). The products obtained were anaꢀ
lyzed by 1Н and 19F NMR methods. Pure compounds were isoꢀ
lated by recrystallization from EtOH. Thiazepine 4а was preꢀ
purified by chromatography on a column with Al2О3 (hexane—
benzene (1 : 1) as eluent). 2ꢀ(Perfluorophenyl)ꢀ4ꢀphenylꢀ2,3ꢀ
dihydrobenzo[b][1,5]thiazepine (4а), 2ꢀ(phenyl)ꢀ4ꢀ[2,3,5,6ꢀtetꢀ
rafluoroꢀ4ꢀ(2ꢀaminophenylthio)phenyl]ꢀ2,3ꢀdihydrobenzo[b]ꢀ
[1,5]thiazepine (4b), and 2ꢀ(perfluorophenyl)ꢀ4ꢀ[2,3,5,6ꢀtetꢀ
rafluoroꢀ4ꢀ(2ꢀaminophenylthio)phenyl]ꢀ2,3ꢀdihydrobenzo[b]ꢀ
[1,5]thiazepine (4с) were obtained.
to the βꢀC atom of chalcone, and the reaction is reversꢀ
ible. The reactions of polyfluorochalcones with oꢀaminoꢀ
thiophenol zinc salt (3) in DMF at 20 °C proceed excluꢀ
sively via nucleophilic substitution of the fluorine atom in
the paraꢀposition of the perfluorophenyl rings.
Experimental
NMR spectra were recorded on a Bruker AVꢀ300 instrument
at the frequencies 300.13 (1Н) and 282.37 (19F) MHz in CDCl3
relative to the signals of residual protons of CDCl3 (1Н, δ
=
H
= 7.24) and C6F6 (19F). IR spectra were obtained on a Vector 22
instrument in CDCl3.
βꢀThiaꢀadducts 5а—d (general procedure). oꢀAminothiopheꢀ
nol (2) (138 mg, 1.1 mmol) was added to a suspension of chalꢀ
cone 1а—c (1 mmol) in MeOH (15 mL). The reaction mixture
was magnetically stirred at room temperature (for 6 h in the case
of 1а, for 3 h in the case of 1b—c). To isolate compounds 5а and
5с, the reaction mixture was poured onto ice, the precipitate that
formed was filtered off, washed, and dried in air, and 3ꢀ(2ꢀaminoꢀ
phenylthio)ꢀ3ꢀ(perfluorophenyl)ꢀ1ꢀphenylpropanꢀ1ꢀone (5a),
and 3ꢀ(2ꢀaminophenylthio)ꢀ1,3ꢀbis(perfluorophenyl)propanꢀ1ꢀ
one (5с) were obtained. To isolate 3ꢀ(2ꢀaminophenylthio)ꢀ1ꢀ
(perfluorophenyl)ꢀ3ꢀphenylpropanꢀ1ꢀone (5b), the precipitate
formed in the reaction mixture was filtered off, washed, and
dried in air; an additional amount of compound 5b was precipiꢀ
tate with water from the filtrate. Under the above described
conditions, the reaction of chalcone 1с with oꢀaminothiophenol
(2) (2 mol) afforded a mixture of compound 5с and 3ꢀ(2ꢀaminoꢀ
phenylthio)ꢀ1ꢀ[4ꢀ(2ꢀaminophenylthio)ꢀ2,3,5,6ꢀtetrafluoropheꢀ
nyl]ꢀ3ꢀ(perfluorophenyl)propanꢀ1ꢀone (5d) in the ratio 2 : 1.
paraꢀSubstituted thiaꢀadduct 5d was isolated from this mixture
by recrystallization from EtOH.
GLꢀMS analysis was carried out on an Agilent Technologies
instrument including an Agilent 6890N gas chromatograph and
an Agilent 5973N GLꢀMS system (EI, 70 eV). Conditions: capꢀ
illary column 30 000×0.25 mm, stationary phase HPꢀ5MS
(0.25 μm), helium as a carrier gas (1 mL min–1); temperature
programming: 2 min at 50 °C, heating from 50 to 280 °C with
a rate of 10 °C min–1, 5 min at 280 °C; temperature of the evapꢀ
orator 280 °C, temperature of the ion source 230 °C, scan rate
1.2 scan s–1 in the mass region 30—800 a.u.
Quantum chemical calculations with full geometry optimiꢀ
zation were performed by the DFT/PBE/3z method using the
PRIRODA program.18
Starting chalcones 1a—с were synthesized according to the
known procedures.16
Commercially available oꢀaminothiophenol (98%) (Acros)
was used. Dimethylformamide was preꢀdried over calcined sieves
3 Å and 9 Å.
Benzothiazepines 4а—с (general procedure). Chalcone 1a—с
(1 mmol) was added to a solution of oꢀaminothiophenol (2)
(2 mmol for 1а,b, 3 mmol for 1с) in MeOH (15 mL), and then
3 droplets of concentrated HCl were added with magnetic stirꢀ
ring. The reaction was refluxed for 3 h and cooled down. To
isolate thiazepines 4a,b, the reaction mixture was poured onto ice
Reaction of chlacone 1a with оꢀaminothiophenol (2) in DMF.
Thiophenol 2 (0.25 g, 2 mmol) was added to a suspension of
chalcone 1a (0.3 g, 1 mmol) in DMF (15 mL). The reaction
mixture was magnetically stirred at room temperature for 4 h

Reactions of polyfluorinated chalcones
Russ.Chem.Bull., Int.Ed., Vol. 60, No. 2, February, 2011
365
Table 2. Conditions of synthesis, yields, melting points, and elemental analysis data for compounds 4a—с, 5a—d, and 6а—с
Starting
chalcone
Ratio
1 : 2
Product
Yield
(%)
M.p./°C
(solvent)
Found
Calculated
Molecular
formula
(%)
C
H
F
N
S
1а
1b
1c
1а
1b
1c
1c
1а
1b
1c
1 : 2
1 : 2
1 : 3
1 : 1
1 : 1
1 : 1
1 : 2
1 : 2
1 : 2
1 : 2
4a
4b
50
88
80
69
81
68
65c
55
73
98
145—147
(ethanol)
120—123
(ethanol)
172—175
(ethanol)
96—99
(hexane)
116—118
(hexane)
109—112b
62.26
62.22
63.40
63.51
54.10
54.00
58.81
59.57
59.83
59.57
49.07
49.13
52.18
52.43
62.69
62.68
62.64
62.68
—
2.98
2.98
3.40
3.55
2.31
2.18
3.31
3.33
3.35
3.33
1.90
1.77
2.43
2.44
3.43
3.26
3.36
3.26
—
23.10
23.43
14.94
14.88
27.93
28.47
22.48
22.44
22.49
22.44
37.08
37.01
27.64
27.64
18.80
18.64
18.90
18.64
—
3.59
3.46
5.75
5.50
4.89
4.67
3.36
3.31
3.26
3.31
2.66
2.73
4.46
4.53
3.28
3.48
3.39
3.48
—
8.40
7.91
12.40
12.56
10.62
10.68
7.43
7.57
7.76
7.57
6.26
6.25
10.32
10.37
8.33
7.97
7.71
7.97
—
C21H12NSF5
C27H18N2S2F4
C27H13N2S2F9
C21H14NOSF5
C21H14NOSF5
C21H9NOSF10
C27H15N2OS2F9
C21H13NOSF4
C21H13NOSF4
C27H14N2OS2F8
4c
5a
5b
5ca
5d
6a
6b
6ce
119—122
(hexane)
134—137d
104—107d
—
a MS, m/z: [M]+, found 513.0235, calculated 513.0240, C21H9NOSF10.
b The product was purified by washing with pentane.
c The content of the compound 5d in the reaction mixture according to the 19F NMR spectral data is presented.
d The compound was isolated in the pure form by column chromatography on Al2O3 (benzene as eluent).
e MS, m/z: [M]+, found 598.0423, calculated 598.0414, C27H14N2OS2F8.
Table 3. 1H and 19F NMR (CDCl3) and IR spectra (CHCl3) of compounds 4a—d, 5a—d, and 6а—с
Comꢀ
pound
1Н NMR,
H (J/Hz)
19F NMR*,
IR,
ν/cm–1
δ
δ
F
4a
4b
3.24 (dd, 1 H, Нa(3), J1 = 13.0, J2 = 5.0); 3.31 (t, 1 Н, Нb(3),
J1 = J2 = 13.0); 5.40 (dd, 1 Н, Н(2), J1 = 13.0, J2 = 5.0);
0.53, 6.81, 22.27
(2 : 1 : 2)
1525 (C—F);
1613 (C=N)
7.16 (td, 1 Harom, J1 = J2 = 7.5, J3 = 1.5); 7.32 (dd, 1 Harom
J1 = 7.5, J2 = 1.5); 7.46—7.56 (m, 4 Harom); 7.61 (br.d, 1 Harom
J = 7.5); 8.06 (m, 2 Harom
,
,
)
2.91 (dd, 1 Н, Нa(3), J1 = 13.0, J2 = 5.0); 3.12 (t, 1 Н, Нb(3),
J1 = J2 = 13.0); 4.48 (br.s, 2 Н, NH2); 5.03 (dd, 1 Н, H(2),
21.37, 28.74
(1 : 1)
1487 (C—F);
1612 (C=N);
J1 = 13.0, J2 = 5.0); 6.71 (m, 2 Harom); 7.13—7.29 (m, 8 Hароm);
3393, 3490 (NH2)
7.47 (td, 1 Harom, J1 = J2 = 7.5, J3 = 1.5); 7.57 (br.d, 1 Harom
J = 7.5); 7.64 (dd, 1 Harom, J1 = 7.5, J2 = 1.5)
,
4c
4d
2.82 (dd, 1 Н, Нa(3), J1 = 13.0, J2 = 5.0); 3.41 (t, 1 Н, Нb(3),
J1 = J2 = 13.0); 4.44 (br.s, 2 Н, NH2); 5.45 (dd, 1 Н, H(2),
J1 = 13.0, J2 = 5.0); 6.69—6.74 (m, 2 Harom); 7.16—7.64 (m, 6 Harom
2.91 (dd, 1 H, Нa(3), J1 = 13.0, J2 = 5.0); 3.15 (t, 1 Н, Нb(3),
J1 = J2 = 13.0); 5.04 (dd, 1 Н, Н(2), J1 = 13.0, J2 = 5.0);
0.69, 7.35, 21.15,
22.54, 29.00
(2 : 1 : 2 : 2 : 2)
0.96, 9.71, 21.31
(2 : 1 : 2)
1468, 1523 (C—F);
1612 (C=N);
3393, 3490 (NH2)
)
6.95—7.67 (m, 9 Н, Harom
)
5a
3.78 (d, 2 H, CН2, J = 7.0); 4.53 (br.s, 2 H, NH2); 5.10 (t, 1 Н,
CН, J1 = J2 = 7.0); 6.55 (t, 1 Harom, J1 = J2 = 7.5); 6.70 (d, 1 Harom
J = 7.5); 7.05—7.17 (m, 2 Harom); 7.42—7.63 (m, 3 Harom); 7.91
(d, 2 Harom, J = 7.5)
–0.62, 6.00, 20.45
(2 : 1 : 2)
1501, 1519 (C—F);
1687 (C=O);
3373, 3485 (NH2)
,
(to be continued)

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Shmuilovich et al.
Table 3 (continued)
Comꢀ
pound
1Н NMR,
H (J/Hz)
19F NMR*,
IR,
ν/cm–1
δ
δ
F
5b
5с
5d
6a
6b
6c
3.49 (d, 2 Н, CН2, J = 7.0); 4.31 (br.s, 2 H, NH2); 4.60 (t, 1 Н,
CН, J1 = J2 = 7.0); 6.54 (td, 1 Harom, J1 = J2 = 8.0, J3 = 1.5);
1.93, 13.12, 21.38
(2 : 1 : 2)
1495, 1522 (C—F);
1711 (C=O);
3374, 3480 (NH2)
6.67 (dd, 1 Harom, J1 = 8.0, J2 = 1.5); 7.04—7.27 (m, 7 Harom
)
3.67 (d, 2 H, CН2, J = 7.0); 4.44 (br.s, 2 H, NH2); 5.03 (t, 1 Н,
CН, J1 = J2 = 7.0); 6.56 (t, 1 Harom, J1 = J2 = 8.0); 6.70 (d, 1 Harom
J = 8.0); 7.06 (d, 1 Harom, J = 8.0); 7.14 (t, 1 Harom, J1 = J2 = 8.0)
–0.14, 2.46, 6.69,
14.20, 20.47, 21.59
(2 : 2 : 1 : 1 : 2 : 2)
,
3.64 (d, 2 H, CН2, J = 7.0); 4.40 (br.s, 4 H, 2 NH2); 5.00 (t, 1 Н,
CН, J1 = J2 = 7.0); 6.55 (t, 1 Harom, J1 = J2 = 8.0); 6.70 (m, 3 Harom);
7.01—7.21 (m, 3 Harom); 7.54 (d, 1 Harom, J = 8.0)
–0.23, 6.79, 20.46,
21.06, 29.36
(2 : 1 : 2 : 2 : 2)
4.43 (с, 2 H, NH2); 6.63—6.75 (m, 2 Harom); 7.17 (t, 1 Harom
,
22.84, 27.75
(1 : 1)
1477 (C—F);
1671 (C=O);
3394, 3481 (NH2)
J1 = J2 = 8.0); 7.44—7.66 (m, 4 Harom); 7.99 (d, 2 Harom, J = 8.0);
7.77, 7.83 (AB system, 2 Н, СН=СН)
4.45 (br.s, 2 H, NH2); 6.55—7.65 (m, 11 Н, СН=СН, 9 Harom
)
21.15, 29.25
(1 : 1)
1469 (C—F);
1657 (C=O);
3393, 3491 (NH2)
4.40 (br.s, 4 H, 2 NH2); 6.55—7.68 (m, 10 Н, СН=СН, 8 Harom
)
21.36, 23.28,
27.62, 29.29
(1 : 1 : 1 : 1)
1469 (C—F);
1635(C=O);
3383, 3473 (NH2)
* The intensity ratio is given in parentheses.
and poured onto ice. The precipitate that formed was filtered
off, washed with water, and dried in air. According to the data of
1Н and 19F NMR spectroscopy, the isolated precipitate (0.39 g)
contained a mixture of compounds 6a and 5a in the ratio 9 : 1.
Conversion of thiaꢀadducts 5a—с. Three droplets of concenꢀ
trated HCl were added to a solution of compound 5a—с (0.3 g)
in MeOH (15 mL) and the mixture was refluxed for 3 h, cooled,
and poured onto ice. In the case of the starting compound 5а,
the precipitate that formed was filtered off, washed with water,
and dried in air. Oily residues that formed from thiaꢀadducts
5b—с were extracted with diethyl ether and the extract was dried
with CaCl2 and evaporated. The reaction products were analyzed
by 1Н and 19F NMR methods.
4с, 5с, and 5d). The product, whose molecular weight correꢀ
sponded to benzothiazepine 4е, was found in the reaction mixꢀ
ture by the LCꢀMS method.
Reactions of chalcones 1a—с with oꢀaminothiophenol zinc salt
(general procedure). oꢀAminothiophenol zinc salt (3) (380 mg,
2 mmol) was added to a suspension of chalcone 1а—с (1 mmol)
in DMF (20 mL). The mixture was magnetically stirred at room
temperature for 5 h and poured onto ice. The precipitate that
formed was filtered off and dissolved in diethyl ether. A residue
of the zinc salt was filtered off and the filtrate was dried with
MgSO4 and evaporated. The products were isolated by chromaꢀ
tography on a column with Al2O3 (benzene as eluent). 3ꢀ[4ꢀ(2ꢀ
Aminophenylthio)ꢀ2,3,5,6ꢀtetrafluorophenyl]ꢀ1ꢀphenylpropꢀ2ꢀ
enꢀ1ꢀone (6a), 1ꢀ[4ꢀ(2ꢀaminophenylthio)ꢀ2,3,5,6ꢀtetrafluoroꢀ
phenyl]ꢀ3ꢀphenylpropꢀ2ꢀenꢀ1ꢀone (6b), and 1,3ꢀbis[4ꢀ(2ꢀ
aminophenylthio)ꢀ2,3,5,6ꢀtetrafluorophenyl]propꢀ2ꢀenꢀ1ꢀone
(6с) were obtained.
The reaction mixture obtained in the case of compound 5b
was separated by chromatography on Al2O3: at first, column
chromatography (hexane as eluent) and then preparative TLC
(benzene—hexane (1 : 1) mixture as eluent) were used. Two fracꢀ
1
tions were obtained, which contained according to the H and
19F NMR spectral data 3ꢀ(perfluorophenyl)ꢀ1ꢀphenylpropꢀ2ꢀenꢀ
1ꢀone (1b) and 4ꢀ(perfluorophenyl)ꢀ2ꢀphenylꢀ2,3ꢀdihydroꢀ
benzo[b][1,5]thiazepine (4d) (fraction 1) and substituted in the
fluorinated ring benzothiazepine 4b and 1ꢀ[4ꢀ(2ꢀaminophenylꢀ
thio)ꢀ2,3,5,6ꢀtetrafluorophenyl]ꢀ3ꢀphenylpropꢀ2ꢀenꢀ1ꢀone (6b)
(fraction 2). Compounds 1b, 4b, and 6b were identified in mixꢀ
References
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Received June 30, 2010;
in revised form November 12, 2010