Unusual oxidative dehydration of vic-[alkyl(aryl)thio]-substituted aromatic (heteroaromatic) carboxamides

Article abstract of DOI:10.1023/B:RUCB.0000037864.52793.92

A new procedure was developed for the synthesis of nitriles of vic-[alkyl(aryl)sulfonyl] derivatives of benzoic, anthraquinonecarboxylic, and 4-isothiazolecarboxylic acids by the reactions of the corresponding vic-[alkyl(aryl)thio]-substituted aromatic (h

Full text of DOI:10.1023/B:RUCB.0000037864.52793.92

916
Russian Chemical Bulletin, International Edition, Vol. 53, No. 4, pp. 916—924, April, 2004
Unusual oxidative dehydration of
vicꢀ[alkyl(aryl)thio]ꢀsubstituted aromatic (heteroaromatic) carboxamides
P. G. Kislitsyn,a F. A. Kucherov,aꢀ L. N. Chukhrov,a S. G. Zlotin,a Z. A. Starikova,b and F. M. Dolgushinb
aN. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences,
47 Leninsky prosp., 119991 Moscow, Russian Federation.
Fax: +7 (095) 135 5328. Eꢀmail: zlotin@ioc.ac.ru
bA. N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences,
28 ul. Vavilova, 119991 Moscow, Russian Federation.
Fax: +7 (095) 135 5085. Eꢀmail: star@xray.ineos.ac.ru
A new procedure was developed for the synthesis of nitriles of vicꢀ[alkyl(aryl)sulfonyl]
derivatives of benzoic, anthraquinonecarboxylic, and 4ꢀisothiazolecarboxylic acids by the reꢀ
actions of the corresponding vicꢀ[alkyl(aryl)thio]ꢀsubstituted aromatic (heteroaromatic)
carboxamides with chlorine in organic solvents containing 20—65% of water. Oxidative deꢀ
hydration of 1ꢀ(butylthio)anthraquinoneꢀ2ꢀcarboxamide afforded 1ꢀbutylꢀ6,11ꢀdihydroꢀ3Hꢀ
4
1λ ꢀanthra[2,1ꢀd]isothiazoleꢀ3,6,11ꢀtrione 1ꢀoxide as a byꢀproduct. The structure of the latter
was established by Xꢀray diffraction analysis. The reaction scheme involving the formation of
Sꢀchlorosulfonium chlorides followed by their hydrolysis was proposed.
Key words: vicꢀ[alkyl(aryl)thio]arenecarboxamides, vicꢀ[alkyl(aryl)sulfonyl]arenecarboꢀ
nitriles, sulfoximides, oxidative dehydration.
vicꢀ[Alkyl(aryl)sulfonyl]ꢀsubstituted aromatic (heteroꢀ
We studied this reaction for derivatives of benzamide
(4a—f), anthraquinoneꢀ2ꢀcarboxamide (5a—d), and isoꢀ
thiazoleꢀ4ꢀcarboxamide (6a—e) using AcOH, CF3COOH,
DMF, and the ionic liquid 1ꢀbutylꢀ3ꢀmethylimidazolium
tetrafluoroborate [bmim][BF4] as the solvents. The water
content was varied from 20 to 65% (v/v).
In all cases, the corresponding vicꢀ[alkyl(aryl)sulfoꢀ
nyl]arenecarbonitriles 7—9 were isolated as the major reꢀ
action products in 35—84% yields (Scheme 2).
aromatic) carbonitriles (1) are valuable intermediates for
the preparation of sulfurꢀcontaining fused heterocycles,
in particular, by the Thorpe reaction.1 Generally, comꢀ
pounds 1 are synthesized from readily available aromatic
(heteroaromatic) carboxylic acid derivatives (esters 2 or
amides 3) containing the vicinal alkylꢀ or arylthio group
by oxidation of the S atom in compounds 2 or 3 with
2
H2O2 followed by the transformation of the ester or
amide group into the nitrile fragment3 (Scheme 1).
In the case of 3,5ꢀbis(methylthio)isothiazoleꢀ4ꢀcarbꢀ
oxamide (6e), both alkylthio groups were oxidized to give
bisꢀsulfone 9e.
Scheme 1
Oxidative dehydration of anthraquinonecarboxamides
5a—d afforded nitriles 8a—d along with byꢀproducts,
which have virtually identical chromatographic mobilities
(Rf = 0.33—0.38, SiO2; ethyl acetate—toluene, 1 : 4) irreꢀ
spective of the nature of the substituent R1 and are, preꢀ
sumably, of similar chemical nature. These byꢀproducts
are unstable under conditions of chromatography on silica
gel, which did not allow us to isolate all compounds of this
type in pure state. Nevertheless, we succeeded in isolating
the byꢀproduct of oxidative dehydration of amide 5c
(R1 = Bun), viz., compound 10, in low yield (∼3%) and
established its structure. Cyclic sulfoximides containing
the S and N atoms in the fiveꢀmembered heterocyclic ring
are known in the 3ꢀoxobenzo[d]isothiazole series.4,5 Comꢀ
pound 10 is, to our knowledge, the first representative of
fused sulfoximides of the anthraquinoneisothiazole series.
We found that vicꢀ[alkyl(aryl)thio]arenecarboxamides
3 can be transformed into nitriles 1 in one step under the
action of chlorine in organic solvents containing water.
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 4, pp. 879—886, April, 2004.
1066ꢀ5285/04/5304ꢀ0916 © 2004 Plenum Publishing Corporation

Oxidative dehydration of 2ꢀ(SR)arenecarboxamides Russ.Chem.Bull., Int.Ed., Vol. 53, No. 4, April, 2004
917
Scheme 2
Table 1. Yields and ratios of products 8c and 10 prepared by
oxidative dehydration of amide 5c in various solvents
Solvent
ET(30)
/kcal mol–1
Percenꢀ
tage
Total
yield of
8c : 10
of H2O 8c and 10
%
DMF
DMF
[bmim][BF4]
CF3COOH
43.2 6
43.2 6
52.5 7
∼59*
50
65
20
50
62
57
80
86
3 : 1
2 : 1
1 : 1
1 : 1
* We did not find the experimental value of ET(30) for
CF3COOH in chemical literature. The value given in Table 1
was estimated by comparing ET(30) for MeCH2OH (51.9),
CF3CH2OH (59.8), and MeCOOH (51.7).6
Oxidative dehydration of vicꢀ[alkyl(aryl)thio]ꢀsubstiꢀ
tuted aromatic (heteroaromatic) carboxamides 4—6 with
chlorine in aqueous organic solvents proceeds apparently
through the formation of Sꢀchlorosulfonium chlorides (11)
followed by their hydrolysis. This assumption is consisꢀ
tent with the known data on the formation of sulfoxides in
the reactions of sulfides with chlorinating agents (Cl2,9,10
NCS,11 trichloroisocyanuric acid12) in the presence of
water. Sulfoxides 12 thus formed undergo subsequent
chlorination at the N or S atom to form intermediates
which are transformed into the final reaction products
through deprotonation and (or) elimination of HCl
(Scheme 3). Based on the available experimental data, it
is impossible to unambiguously choose one particular diꢀ
rection of chlorination. However, these data demonstrate
that the amide group can sometimes exhibit dual reactivꢀ
ity in the reaction under consideration and react with the
vicinal sulfoxide group with involvement of either the O
or N atom to give nitriles 7—9 or sulfoximides 10, respecꢀ
tively, as the final products.
Comꢀ
pound
R2
R3
Comꢀ
pound
R1
Comꢀ R2
pound
R3
4, 7
а
b
c
d
5, 8
a
b
c
d
6, 9
Et
Prn
nꢀC8H17
Ph
H
H
H
H
Me
Et
Bun
Ph
a
b
c
d
Me
Me
Bun
Me
OMe
Cl
OMe
Ph
e
f
H
e
Me SMe (6),
SO2Me (9)
This reaction scheme was confirmed by the synthesis
of products 7a—d,g,h from sulfoxides 12a—d,g,h, which
were prepared by the independent method (oxidation of
sulfides 4 with hydrogen peroxide), under the action of
chlorine.* This transformation proceeds smoothly both in
the presence of water and under anhydrous conditions,
which is evidence for the intramolecular character of oxiꢀ
dation of the S atom (Scheme 4).
Ph
NO2
Reagents and conditions: i. Cl2, organic solvent—water.
The 8c : 10 ratio (Table 1), which was determined
from the integral intensity ratio of the signals for the SCH2
protons in the H NMR spectrum of the crude product,
1
depends on the solvent used. The percentage of heteroꢀ
cycle 10 increases in the series of DMF, [bmim][BF4],
and CF3COOH in parallel with the increase in their poꢀ
larity characterized by the Dimroth—Reichardt ET(30)
parameter.6
The percentage of sulfoximide 10 produced in the
reaction in aqueous DMF slightly increases as the water
content increases (ET(30)H O = 63.1 kcal mol–1),8 which
also indicates that the polar2reaction medium has a favorꢀ
able effect on heterocyclization.
The elucidation of the structures of reaction products
7—10 requires additional comments. Recently,15 we have
erroneously assigned the structures of isomeric fused
* The structures of compounds 12a—c,g as Sꢀoxides were proved
1
by the fact that the H NMR spectra of these compounds show
nonequivalent signals for the diastereotopic protons of the
methylene group bound to the S atom (Table 2). The structures
of compounds 12d,h were confirmed by the presence of a moꢀ
lecular ion peak in their mass spectra (Table 3).

918
Russ.Chem.Bull., Int.Ed., Vol. 53, No. 4, April, 2004
Kislitsyn et al.
Scheme 3
Scheme 4
Compound
R
Yield (%)
4, 7, 12
12
96
81
90
91
81
7
96
82
84
86
82
a
b
c
d
g
Et
Pr
nꢀC8H17
Ph
Bun
h
82
79
Reagents and conditions: i. H2O2, AcOH; ii. Cl2, AcOH.
spectra of these compounds, which is comparable with
the intensity of the noise signals. The true structures of
compounds 7—10 were established by chemical methods
and Xꢀray diffraction analysis. For example, oxidative
dehydration products 7a,d and 9a,b are identical to comꢀ
pounds prepared independently from nitriles 14a,d and
15a,b, respectively, under the action of 30% H2O2 in
AcOH or mꢀCPBA in CH2Cl2 (Scheme 5). The structure
of compounds 9c,e, whose melting points differ substanꢀ
tially from that published in the literature, were conꢀ
firmed by the results of 1H NMR spectroscopy, mass specꢀ
trometry, and elemental analysis (see Tables 2 and 3).
The structure of compound 8d, whose indepenꢀ
dent synthesis is difficult to perform because the corꢀ
responding nitrile is hardly accessible, and the strucꢀ
ture of sulfoximide 10 were unambiguously estabꢀ
lished by Xꢀray diffraction analysis (Figs. 1 and 2, respecꢀ
tively).
sulfoximines 13 to compounds 7a—d,f based on the reꢀ
sults of IR and H NMR spectroscopy, mass spectromꢀ
etry, and elemental analysis. The erroneous interpretaꢀ
tion of the experimental data resulted primarily from the
very low intensity of the signal of the C≡N group in the IR
To summarize, we developed a convenient oneꢀpot
synthesis of vicꢀ[alkyl(aryl)sulfonyl]ꢀsubstituted aromatic
(heteroaromatic) carbonitriles by oxidative dehydration
of vicꢀ[alkyl(aryl)thio]ꢀsubstituted aromatic (heteroꢀ
aromatic) carboxamides with chlorine in organic solvents
1

Oxidative dehydration of 2ꢀ(SR)arenecarboxamides Russ.Chem.Bull., Int.Ed., Vol. 53, No. 4, April, 2004
919
Scheme 5
containing 20—65% of water and synthesized the first
representative of fused sulfoximides of the anthraisoꢀ
thiazole series.
Experimental
1
The H NMR spectra were recorded on a Bruker AMꢀ300
spectrometer (300.13 MHz) in DMSOꢀd6. The chemical shifts
were measured relative to Me4Si as the internal standard. The
mass spectra were obtained on an MSꢀ30 instrument (Kratos) in
the electron impact mode (70 eV). The TLC analysis was carried
out on Silufol UVꢀ250 plates in a 1 : 4 ethyl acetate—toluene
system. Compounds 4a—f,15 5a—d,16 6e, and 15a,b 14,17 were
synthesized according to procedures published in the literature.
Compounds 6a—d were prepared for the first time according to
a procedure described earlier.14 The solvents were purified using
standard procedures.18 The ionic liquid [bmim][BF4] was preꢀ
pared according to a known procedure.19
The yields, melting points, 1H NMR spectroscopic data,
and the results of elemental analysis for the compounds syntheꢀ
sized are given in Table 2. The massꢀspectrometric characterisꢀ
tics of compounds 9a—e are listed in Table 3.
Comꢀ
R
Yield (%)
Comꢀ
R1
R2
Yield
Single crystals of compounds 8c and 10 suitable for Xꢀray
diffraction analysis were prepared by crystallization from a 4 : 1
toluene—ethyl acetate system. The crystallographic data and
the main details of structure refinement are given in Table 4.
The Xꢀray diffraction data for compound 8c were collected on a
Bruker SMART CCDꢀ1000 diffractometer equipped with a twoꢀ
coordinate detector (MoꢀKα radiation, λ = 0.71073 Å, ω scanꢀ
pound
pound
9
(%)
14
7
4, 7, 14
а
d
9, 15
a
b
Et
Ph
97
89
86
80
Me OMe
Me Cl
40
52
Reagents and conditions: i. POCl3; ii. H2O2; AcOH; iii. H2O2,
AcOH (15a); iv. mꢀChloroperoxybenzoic acid, CH2Cl2 (15b).
Table 2. Yields, melting points, results of microanalysis, and 1H NMR spectroscopic data for the compounds synthesized
Comꢀ Yield
pound (%)
M.p.
/°C
Found
Calculated
Molecular
formula
1H NMR
(δ, J/Hz)
(%)
С
H
N
S
6а
6b
6с
66
58
74
156—160
145—147
173—175
35.33 4.03 13.70 31.27 C6H8N2O2S2
35.28 3.95 13.71 31.40
28.61 2.63 13.12 30.91 C5H5ClN2OS2 2.61 (s, 3 H, SMe); 7.70, 7.83 (both br.s,
28.78 2.41 13.42 30.73 1 H each, NH)
43.75 5.75 11.28 26.11 C9H14N2O2S2 0.91 (t, 3 H, (CH2)3CH3, J = 7.4); 1.43 (m, 2 H,
3.20 (s, 3 H, OMe); 4.01 (s, 3 H, SMe);
7.05, 7.35 (both br.s, 1 H each, NH)
43.88 5.73 11.37 26.03
(CH2)2CH2Me); 1.68 (m, 2 H, CH2CH2CH2Me);
2.89 (t, 2 H, CH2(CH2)2Me, J = 6.6); 3.29 (s, 3 H,
OMe); 7.46, 8.23 (both br.s, 1 H each, NH)
6d
7a
87
193—196
49.69 3.71 10.48 24.18 C11H10N2O2S2 3.41 (s, 3 H, SMe); 7.36—7.50 (m, 3 H, Ph);
49.60 3.78 10.52 24.08
7.61—7.74 (m, 3 H, Ph, NH); 7.79 (br.s, 1 H, NH)
1.22 (t, 3 H, Me, J = 7.0); 3.59 (q, 2 H, CH2,
J = 7.0); 8.50 (d, 1 H, H(6), J = 8.0); 8.67 (s, 1 H,
H(3)); 8.71 (d, 1 H, H(5), J = 8.0)
68, 86*, 153—154
96**
45.12 3.38 11.60 13.28 C9H8N2O4S
45.00 3.36 11.66 13.35
7b
7c
79, 82** 119—121
65, 84** 100—102
47.29 3.91 10.91 12.52 C10H10N2O4S 0.97 (t, 3 H, Me, J = 7.0); 1.69 (m, 2 H, CH2);
47.24 3.96 11.02 12.61
3.57 (m, 2 H, SCH2); 8.49 (d, 1 H, H(6), J = 8.0);
8.67 (s, 1 H, H(3)); 8.70 (d, 1 H, H(5), J = 8.0)
55.62 6.20 8.76 10.11 C15H20N2O4S 0.85 (t, 3 H, Me, J = 7.0); 1.24 (m, 8 H, 4 CH2);
55.54 6.21 8.64 9.88
1.36 (m, 2 H, Me); 1.65 (m, 2 H, CH2); 3.57
(m, 2 H, SCH2); 8.50 (d, 1 H, H(6), J = 8.0); 8.67
(s, 1 H, H(3)); 8.71 (d, 1 H, H(5), J = 8.0)
(to be continued)

920
Russ.Chem.Bull., Int.Ed., Vol. 53, No. 4, April, 2004
Kislitsyn et al.
Table 2 (continued)
Comꢀ Yield
pound (%)
M.p.
/°C
Found
Calculated
Molecular
formula
1H NMR
(δ, J/Hz)
(%)
С
H
N
S
7d
7e
71, 80*, 144—147
86**
54.35 2.89 9.53 11.19 C13H8N2O4S
54.16 2.80 9.72 11.12
7.71 (t, 2 H, mꢀPh, J = 7.5), 7.82 (t, 1 H, pꢀPh,
J = 7.5); 8.09 (d, 2 H, oꢀPh, J = 7.5); 8.42 (d, 1 H,
H(6), J = 8.5); 8.66 (s, 1 H, H(3)); 8.89 (d, 1 H,
H(5), J = 8.5)
84
69
186—189
160—162
51.07 2.22 8.96 10.41 C13H7FN2O4S 7.56 (t, 2 H, CH, JH,H = 8.0, JH,F = 8.0); 8.19 (dd,
50.98 2.30 9.15 10.47
2 H, CH, JH,H = 8.0, JH,F = 4.8); 8.42 (d, 1 H,
H(6), J = 8.2); 8.65 (d, 1 H, H(5), J = 8.2); 8.80
(s, 1 H, H(3))
7.75 (t, 2 H, mꢀPh, J = 7.5); 7.93 (d, 1 H, pꢀPh,
J = 7.5); 8.23 (d, 2 H, oꢀPh, J = 7.5); 9.21 (s, 1 H,
H(5)); 9.49 (s, 1 H, H(7))
7f
46.67 2.34 12.53 9.56
46.85 2.12 12.61 9.62
C13H7N3O6S
7g
82** 110—113
79** 162—166
49.19 4.31 10.35 11.78 C11H12N2O4S 0.87 (t, 3 H, Me, J = 7.0); 1.39, 1.64 (both m,
49.24 4.51 10.44 11.95
2 H each, CH2); 3.59 (m, 2 H, SCH2); 8.50
(d, 1 H, H(6), J = 8.0); 8.67 (s, 1 H, H(3)); 8.71
(d, 1 H, H(5), J = 8.0)
7h
55.71 3.21 8.97 10.82 C14H10N2O4S 2.40 (s, 3 H, Me); 7.52, 7.97 (both d, 2 H each,
55.62 3.33 9.27 10.61
CH, J = 8.0); 8.40 (d, 1 H, H(6), J = 8.0);
8.63 (d, 1 H, H(5), J = 8.0); 8.85 (s, 1 H, H(3))
3.83 (s, 3 H, Me); 7.72—8.25 (m, 4 H, H(5), H(6),
H(7), H(8)); 8.36—8.68 (m, 2 H, H(3), H(4))
1.44 (t, 3 H, Me, J = 6.2); 4.07 (q, 2 H, CH2,
J = 6.2); 7.90—8.00 (m, 2 H, H(6), H(7));
8.02—8.18 (m, 2 H, H(5), H(8)); 8.47, 8.56
(both d, 1 H each, H(3) or H(4), J = 8.3)
0.93 (t, 3 H, Me, J = 6.2); 1.48 (m, 2 H,
(CH2)2CH2Me); 1.86 (m, 2 H, CH2CH2CH2Me);
4.03 (t, 2 H, CH2(CH2)2Me, J = 6.2); 7.86—8.27
(m, 4 H, H(5), H(6), H(7), H(8)); 8.45, 8.53
(both d, 1 H each, H(3) or H(4), J = 7.1)
7.67—8.01 (m, 5 H, H(6), H(7), Ph); 8.05—8.24
(m, 4 H, H(5), H(8), Ph); 8.50, 8.77 (both d,
1 H each, H(3) or H(4), J = 7.3)
8a
8b
35
34
311—313
249—251
61.51 2.83 4.66 10.17 C16H9NO4S
61.73 2.91 4.50 10.30
62.72 3.52 4.06 10.11 C17H11NO4S
62.76 3.41 4.31 09.86
8c
35
39
201—203
306—308
64.62 4.16 4.03 9.29
64.57 4.28 3.96 9.07
C19H15NO4S
8d
9a
67.79 2.81 3.93 8.52
67.55 2.97 3.75 8.59
C21H11NO4S
51, 164—169
33.12 2.82 12.62 29.11 C6H6N2O3S2
3.59 (s, 3 H, OMe); 4.08 (s, 3 H, SO2Me)
40*** (lit. data13: 33.02 2.77 12.84 29.38
167—168)
9b
9c
35, 52* 139—142
26.53 1.25 12.73 29.01 C5H3ClN2O2S2 3.64 (s, 3 H, SO2Me)
26.97 1.36 12.58 28.80
41.58 4.41 10.95 24.44 C9H12N2O3S2 0.97 (t, 3 H, (CH2)3CH3, J = 7.2); 1.50 (m, 2 H,
38
83—84
(lit. data13: 41.52 4.65 10.76 24.63
51—52)
(CH2)2CH2Me); 1.84 (m, 2 H, CH2CH2CH2Me);
3.40 (t, 2 H, CH2(CH2)2Me, J = 7.9); 4.16 (s,
3 H, Me)
9d
9e
81
61
155—157
240—241
50.13 3.25 10.48 24.13 C11H8N2O2S2 3.66 (s, 3 H, SO2Me); 3.62 (m, 3 H, Ph); 7.94
49.98 3.05 10.60 24.26
(m, 2 H, Ph)
26.87 2.23 10.31 36.43 C6H6N2O4S3
(lit. data14: 27.06 2.27 10.52 36.12
212—214)
3.55, 3.70 (both s, 3 H each, Me)
10
3
246—249
64.72 4.23 3.71 9.12
64.57 4.28 3.96 9.07
C19H15NO4S
0.80 (t, 3 H, Me, J = 6.2); 1.36 (m, 2 H,
(CH2)2CH2Me); 1.86 (m, 2 H, CH2CH2CH2Me);
4.17, 4.29 (both m, 1 H each, CH2(CH2)2Me);
7.86—8.27 (m, 4 H, H(7), H(8), H(9), H(10)); 8.33,
8.66 (both d, 1 H each, H(4) or H(5), J = 7.5)
(to be continued)

Oxidative dehydration of 2ꢀ(SR)arenecarboxamides Russ.Chem.Bull., Int.Ed., Vol. 53, No. 4, April, 2004
Table 2 (continued)
921
Comꢀ Yield
pound (%)
M.p.
/°C
Found
Calculated
Molecular
formula
1H NMR
(δ, J/Hz)
(%)
С
H
N
S
12a
12b
96
81
196—200
193—196
44.47 4.19 11.33 13.40 C9H10N2O4S
44.62 4.16 11.56 13.24
1.21 (t, 3 H, Me, J = 7.0); 2.75 and 3.26 (both m,
2 H each, CH2S); 7.75 (s, 1 H, NH); 8.18 (d, 1 H,
H(6), J = 8.0); 8.36 (d, 1 H, H(5), J = 8.0); 8.39
(s, 1 H, NH); 8.77 (s, 1 H, H(3))
46.92 4.69 10.88 12.64 C10H12N2O4S 1.07 (t, 3 H, Me, J = 7.0); 1.66 and 1.90 (both m,
46.87 4.72 10.93 12.51
2 H each, CH2); 2.61 and 3.24 (both m, 2 H each,
CH2S); 7.79 (s, 1 H, NH); 8.17 (d, 1 H, H(6),
J = 8.0); 8.37 (d, 1 H, H(5), J = 8.0); 8.41 (s,
1 H, NH); 8.80 (s, 1 H, H(3))
12c
90
157—159
55.31 6.61 8.70 9.76
55.19 6.79 8.58 9.82
C15H22N2O4S 0.89 (t, 3 H, Me, J = 7.0); 1.31 (m, 8 H, 4 CH2);
1.41 and 1.45 (both m, 2 H each, CH2); 1.62
and 1.78 (both m, 2 H each, CH2); 2.61 and 3.15
(both m, 2 H each, CH2S); 7.69 (s, 1 H, NH); 8.17
(d, 1 H, H(6), J = 8.0); 8.35 (m, 2 H, H(5) + NH);
8.81 (s, 1 H, H(3))
12d
12g
91
81
245—248
162—164
53.83 3.52 9.69 11.23 C13H10N2O4S 7.92 (m, 3 H, pꢀPh + mꢀPh); 7.70 (d, 2 H, oꢀPh,
53.79 3.47 9.65 11.05
J = 7.5); 7.86 (s, 1 H, NH); 8.08 (d, 1 H, H(6),
J = 8.5); 8.47 (m, 2 H, H(5) + NH); 8.90 (s, 1 H,
H(3))
48.71 5.13 10.48 11.91 C11H14N2O4S 0.97 (t, 3 H, Me, J = 7.0); 1.48 (m, 2 H, CH2); 1.60
48.88 5.22 10.36 11.86
and 1.86 (both m, 2 H each, CH2); 2.62 and 3.27
(both m, 2 H each, CH2S); 7.73 (s, 1 H, NH); 8.16
(d, 1 H, H(6), J = 8.5); 8.32 (m, 2 H, H(5) + NH);
8.80 (s, 1 H, H(3))
12h
82
276—279
55.41 4.04 9.11 10.68 C14H12N2O4S 2.34 (s, 3 H, Me); 7.21 (d, 2 H, CH, J = 8.5);
55.25 3.97 9.21 10.54
7.62 (d, 2 H, CH, J = 8.5); 7.72 (s, 1 H, NH);
8.09 (d, 1 H, H(6), J = 8.8); 8.30 (s, 1 H, NH);
8.33 (d, 1 H, H(5), J = 8.8); 8.91 (s, 1 H, H(3))
1.43 (t, 3 H, Me, J = 6.6); 3.24 (q, 2 H, CH2,
J = 6.6); 8.02 (d, 1 H, H(6), J = 9.8); 8.08 (d, 1 H,
H(5), J = 9.8); 8.16 (s, 1 H, H(3))
14a
14d
97
89
131—133
139—142
52.21 3.62 13.56 15.42 C9H8N2O2S
51.91 3.87 13.45 15.40
61.19 3.01 11.14 12.20 C13H8N2O2S
60.92 3.15 10.93 12.51
7.61 (m, 3 H, pꢀPh + mꢀPh); 7.63 (d, 2 H, oꢀPh,
J = 7.5); 7.73 (s, 1 H, H(3)); 8.15 (d, 1 H, H(6),
J = 8.3); 8.19 (d, 1 H, H(5), J = 8.3)
* The yields of 7a,d and 9b in the reactions of nitriles 14a,d and 15b with H2O2 in AcOH.
** The yields of 7a—d,g,h in the reactions of sulfoxides 12a—d,g,h with Cl2 in AcOH.
*** The yield of 9a in the reaction of nitrile 15a with mꢀCPBA in CH2Cl2.
Table 3. Characteristics of the mass spectra of compounds 9a—e
and 12d,h
ning technique, scan step was 0.3°, frames were exposed for 10 s).
The Xꢀray data for compound 10 were collected on a Syntex P21
diffractometer (MoꢀKα radiation, λ = 0.71073 Å). Both strucꢀ
tures were solved by direct methods. The positions and therꢀ
mal parameters of the nonhydrogen atom were refined first
isotropically and then anisotropically by the fullꢀmatrix leastꢀ
squares method. The H atoms in the structure of 8c were
placed in geometrically calculated positions and refined using
the riding model. The H atoms in the structure of 10 were
located from a difference electron density map and refined
isotropically. In the structure of 8c, the butyl group is disordered
over two positions with occupancies of 0.7/0.3 (in Fig. 1, the
minor component is shown by gray lines). All calculations were
carried out on a personal computer using the SHELXTL proꢀ
gram package.20
Comꢀ
pound
MS (EI, 70 eV),
m/z (Irel (%))
9а
9b
9c
9d
9e
218 [М]+ (61), 203 (5), 189 (14), 171 (3)
224 [М]+ (12), 222 [М]+ (27), 207 (7), 191 (2), 175 (3)
260 [М]+ (7), 233 (1), 205 (4), 195 (14)
264 [М]+ (16), 217 (1), 200 (9)
266 [М]+ (10), 251 (2), 235 (1), 204 (36)
290 [M]+ (5), 274 (2), 213 (7), 197 (100), 167 (7),
151 (20), 125 (15), 109 (10), 77 (25)
304 [M]+ (4), 288 (4), 213 (3), 197 (100), 167 (5),
151 (15), 139 (35), 123 (10), 91 (20), 77 (10)
12d
12h

922
Russ.Chem.Bull., Int.Ed., Vol. 53, No. 4, April, 2004
Kislitsyn et al.
Table 4. Crystallographic data and parameters of the structure
refinement for compounds 8c and 10
C(18)
C(17´)
C(17)
Parameter
8с
10
C(16)
C(16´)
Molecular formula
Molecular weight
Space group
T/K
a/Å
b/Å
c/Å
α/deg
C19H15NO4S
353.38
P21/c
120(2)
12.605(1)
11.981(1)
10.7513(9)
90
100.104(2)
90
1598.5(2)
4
C19H15NO4S
353.38
P–1
C(15)
O(1)
163(2)
O(4)
8.649(3)
9.320(3)
10.272(3)
82.49(2)
80.91(2)
83.36(2)
806.9(4)
2
O(2)
S(1)
N(1)
C(14)
C(10)
C(1)
C(13)
C(12)
C(9)
C(6)
β/deg
γ/deg
C(19)
V/Å3
C(2)
Z
dcalc/g cm–3
1.468
2.28
60
1.455
2.25
52
µ/cm–1
C(5)
C(8)
C(7)
C(3)
2θmax/deg
Number of independent
C(11)
C(4)
4486 (0.0382)
2907 (0.0173)
O(3)
reflections (Rint
)
R1 (against F for reflections
with I > 2σ(I ))
0.0621 (2151
reflections)
0.1402
0.0382 (2349
reflections)
0.1194
Fig. 1. General view of molecule 8c.
wR2 (against F 2 for
all reflections)
Number of parameters
in refinement
249
286
C(9)
C(10)
C(8)
C(11)
Table 5. Bond lengths (d) and bond angles (ω) in the strucꢀ
ture of 8c
C(12)
C(13)
C(7)
C(6)
Bond
d/Å
Angle
ω/deg
O(4)
O(3)
S(1)—O(1)
S(1)—O(2)
S(1)—C(15) 1.783(3)
S(1)—C(1)
O(3)—C(7)
O(4)—C(10) 1.216(3)
N(1)—C(19) 1.151(4)
C(1)—C(2)
C(1)—C(6)
C(2)—C(19) 1.439(5)
1.426(2)
1.429(2)
O(1)—S(1)—O(2) 118.0(1)
O(1)—S(1)—C(15) 112.0(1)
O(2)—S(1)—C(15) 107.5(2)
O(1)—S(1)—C(1) 107.3(1)
O(2)—S(1)—C(1) 105.0(1)
C(15)—S(1)—C(1) 106.3(1)
C(2)—C(1)—C(6) 118.6(2)
C(2)—C(1)—S(1) 118.4(2)
C(6)—C(1)—S(1) 121.9(2)
C(3)—C(2)—C(1) 120.4(3)
C(3)—C(2)—C(19) 115.6(2)
C(1)—C(2)—C(19) 124.0(3)
N(1)—C(19)—C(2) 171.5(3)
C(1)—C(6)—C(10) 122.1(2)
O(3)—C(7)—C(8) 122.3(3)
O(3)—C(7)—C(5) 119.5(2)
O(4)—C(10)—C(9) 121.5(3)
O(4)—C(10)—C(6) 120.7(3)
O(5)
C(5)
C(14)
C(1)
1.807(3)
1.220(3)
C(16)
C(17)
C(18)
C(19)
C(4)
C(3)
S(1)
1.407(3)
1.408(4)
C(2)
N(1)
C(15)
O(1)
Fig. 2. General view of molecule 10.
The atomic coordinates and thermal parameters were deꢀ
posited with the Cambridge Structural Database. The bond
lengths and bond angles are given in Tables 5 and 6.
Synthesis of 2ꢀ[alkyl(aryl)sulfonyl]ꢀ4ꢀnitrobenzonitriles
(7a—f) (general procedure). A. A weak stream of chlorine was
passed through solutions of vicꢀalkyl(aryl)benzocarboxamides
4a—f (2 mmol) in 60% aqueous AcOH (3 mL) at 20 °C for
10 min (TLC control). The solvent and the excess of chlorine
were removed in vacuo. Cold water (5 mL) was added to the
residue. The precipitates of 7a—f were filtered off, dried in air,
and recrystallized from PriOH.
B. A 30% H2O2 solution (0.2 mL, 1.94 mmol) was added to a
solution of nitrile 14a (14d) (0.48 mmol) in AcOH (5 mL). The
reaction mixture was refluxed for 2 h and the same amount of

Oxidative dehydration of 2ꢀ(SR)arenecarboxamides Russ.Chem.Bull., Int.Ed., Vol. 53, No. 4, April, 2004
923
Table 6. Bond lengths (d) and bond angles (ω) in the strucꢀ
ture of 10
1ꢀoxide (10) (Rf = 0.35) along with 1ꢀbutylsulfonylanthraꢀ
quinoneꢀ2ꢀcarbonitrile 8c (Rf = 0.75).
Synthesis of 3ꢀsubstituted 5ꢀalkylsulfonylisothiazoleꢀ4ꢀcarboꢀ
nitriles (9a—e). A. A weak stream of chlorine was passed with
stirring through suspensions of amides 6a—e (1.96 mmol) in
85% aqueous AcOH (6 mL) at 20 °C for 10 min (TLC control).
Compounds 9a—e were filtered off, washed with water (10 mL),
dried in air, and recrystallized from THF.
B. mꢀChloroperoxybenzoic acid (60% purity, 0.70 g,
2.43 mmol) was added to a solution of nitrile 15a (0.15 g,
0.81 mmol) in CH2Cl2 (4 mL) and the mixture was stirred at
20 °C for 1 h. The solvent was distilled off under reduced
pressure and the precipitate of 9a was recrystallized from
hexane.a
C. A 50% H2O2 solution (0.60 mL, 11.4 mmol) was added to
a solution of the nitrile 15b (0.10 g, 0.52 mmol) in AcOH (2 mL).
The reaction mixture was heated at 50 °C for 4 h. The course of
the reaction was monitored by TLC. The solvent was distilled off
under reduced pressure and the precipitate of 9b was recrystalꢀ
lized from a THF—PriOH mixture.
Synthesis of 2ꢀ[alkyl(aryl)sulfinyl]ꢀ4ꢀnitrobenzamides
(12a—d,g,h) (general procedure). A 30% H2O2 solution (0.5 mL,
4.85 mmol) was added to suspensions of the corresponding
2ꢀalkyl(aryl)thioꢀ4ꢀnitrobenzamide 4a—d,g,h (4 mmol) in glaꢀ
cial AcOH (5 mL) at 5—10 °C. The reaction mixtures were
stirred until the starting compounds were consumed (TLC conꢀ
trol) and poured into water (100 mL). The precipitates of
compounds 12a—d,g,h that formed were filtered off, washed
with water (2×10 mL), dried in air, and recrystallized from
acetone.
Bond
d/Å
Angle
ω/deg
S(1)—O(3)
S(1)—N(1)
S(1)—C(16) 1.775(2)
S(1)—C(1) 1.789(2)
O(1)—C(15) 1.216(2)
N(1)—C(15) 1.376(3)
O(4)—C(13) 1.216(2)
O(5)—C(6)
C(1)—C(2)
C(2)—C(3)
C(2)—C(15) 1.518(3)
C(13)—C(14) 1.493(3)
C(16)—C(17) 1.526(3)
C(17)—C(18) 1.520(3)
C(18)—C(19) 1.501(3)
1.440(2)
1.573(2)
O(3)—S(1)—N(1) 115.41(9)
O(3)—S(1)—C(1) 114.12(9)
O(3)—S(1)—C(16) 110.5(1)
N(1)—S(1)—C(16) 107.4(1)
N(1)—S(1)—C(1)
98.48(9)
C(16)—S(1)—C(1) 110.27(9)
C(15)—N(1)—S(1) 112.2(1)
C(2)—C(1)—C(14) 122.2(2)
C(2)—C(1)—S(1) 105.3(1)
C(14)—C(1)—S(1) 132.0(2)
C(1)—C(2)—C(3) 120.5(2)
C(3)—C(2)—C(15) 127.1(2)
C(4)—C(3)—C(2) 118.5(2)
C(3)—C(4)—C(5) 121.2(2)
C(4)—C(5)—C(14) 120.6(2)
C(4)—C(5)—C(6) 119.0(2)
C(14)—C(5)—C(6) 120.4(2)
O(5)—C(6)—C(7) 121.7(2)
O(5)—C(6)—C(5) 120.4(2)
C(7)—C(6)—C(5) 117.9(2)
O(4)—C(13)—C(12) 122.5(2)
O(4)—C(13)—C(14) 119.7(2)
O(1)—C(15)—N(1) 125.3(2)
O(1)—C(15)—C(2) 123.0(2)
N(1)—C(15)—C(2) 111.7(2)
C(17)—C(16)—S(1) 110.3(1)
1.216(2)
1.383(3)
1.391(3)
Synthesis of 2ꢀ[alkyl(aryl)thio]ꢀ4ꢀnitrobenzonitriles (14a,d)
(general procedure). Phosphorus oxychloride (3.1 mL,
33.83 mmol) was added dropwise to a stirred solution of amide
4a or 4d (25.84 mmol) in DMF (20 mL) at 5 °C. The reaction
mixture was stirred at 20 °C for 2 h and poured onto ice (20 g).
The precipitate of 14a or 14d was filtered off, washed with waꢀ
ter (3×15 mL), dried in air, and recrystallized from an acꢀ
etone—PriOH mixture.
30% H2O2 was added. The mixture was refluxed for 2 h and
concentrated in vacuo. Water (10 mL) was added to the residue.
The precipitate of 7a (7d) was filtered off, washed with waꢀ
ter (3×10 mL), dried in air, and recrystallized from an acꢀ
etone—PriOH mixture.
C. A weak stream of chlorine was passed through solutions of
2ꢀ[alkyl(aryl)sulfinyl]ꢀ4ꢀnitrobenzamides 12a—d,g,h (2 mmol)
in glacial AcOH (3 mL) at 20 °C for 10 min (TLC control). The
solvent and the excess of chlorine were removed in vacuo. Cold
water (5 mL) was added to the residues. The precipitates of
7a—d,g,h were filtered off, dried in air, and recrystallized
from PriOH.
Synthesis of 1ꢀ[alkyl(aryl)sulfonyl]anthraquinoneꢀ2ꢀcarboꢀ
nitriles (8a—d) (general procedure). A weak stream of
chlorine was passed with stirring through solutions of
References
1. F. S. Babichev, Yu. A. Sharanin, V. P. Litvinov, V. K.
Promonenkov, and Yu. M. Volovenko, Vnutrimolekulyarnoe
vzaimodeistvie nitril´noi i CHꢀ, OHꢀ i SHꢀgrupp [Intramolecuꢀ
lar Interactions of the Nitrile Group with the CH, OH, and SH
Groups], Naukova Dumka, Kiev, 1985, 200 pp. (in Russian).
2. B. M. Choudary, B. Bharathi, Ch. Venkat Reddy, and
M. Lakshmi Kantam, J. Chem. Soc., Perkin Trans. 1,
2002, 2069.
3. B. J. Broughton, P. Chaplen, P. Knowles, E. Lunt, S. M.
Marshall, D. L. Pain, and K. R. H. Wooldridge, J. Med.
Chem., 1975, 11, 1117.
4. S. Allenmark, C. Andersson, and P. Widell, Chirality,
1995, 7, 541.
1ꢀ[alkyl(aryl)thio]anthraquinoneꢀ2ꢀcarboxamides
5a—d
(0.96 mmol) in 50% aqueous CF3COOH (6 mL) at 20 °C for
15 min (TLC control). The reaction mixtures were stirred for 4 h
and poured into water (15 mL). The precipitates that formed
were filtered off, washed with water (3×8 mL), dried in air,
recrystallized from a 3 : 1 ethanol—THF mixture, and chromaꢀ
tographed on a column with silica gel (L 40/100; toluene and
then a 2 : 1 toluene—ethyl acetate mixture as the eluent) to
isolate products 8a—d.
5. A. C. Löwendahl and S. G. Allenmark, Chirality,
1997, 9, 167.
Chromatography of the oxidative dehydration product of
1ꢀbutylthioanthraquinoneꢀ2ꢀcarboxamide (5c) afforded 1ꢀbuꢀ
tylꢀ6,11ꢀdihydroꢀ3Hꢀ1λ ꢀanthra[2,1ꢀd]isothiazoleꢀ3,6,11ꢀtrione
6. C. Reichardt, Chem. Rev., 1994, 94, 2319.
7. M. J. Muldoon, C. M. Gordon, and I. R. Dunkin, J. Chem.
Soc., Perkin Trans. 2, 2001, 433.
4

924
Russ.Chem.Bull., Int.Ed., Vol. 53, No. 4, April, 2004
Kislitsyn et al.
8. T. Soujanya, R. W. Fessenden, and A. Samanta, J. Phys.
Chem., 1996, 100, 3507.
9. E. A. Serebryakov, P. G. Kislitsin, V. V. Semenov, and S. G.
Zlotin, Synthesis, 2001, 1659.
17. H.ꢀD. Krebs, Aust. J. Chem., 1989, 42, 1291.
18. A. J. Gordon and R. A. Ford, The Chemist´s Companion,
A WileyꢀInterscience Pulication—John Wiley and Sons, New
York—London—Sydney—Toronto, 1972.
10. J. Drabowicz, W. Midura, and M. Mikolayczyk, Synthesis,
1979, 39.
19. P. A. Z. Suarez, J. E. L. Dullius, S. Einloft, R. F. DeSouza,
and J. Dupont, Polyhedron, 1996, 15, 1217.
11. M. Haake, H. Gebbing, and H. Benack, Synthesis, 1979, 97.
12. Z.ꢀX. Xiong, N.ꢀP. Huang, and P. Zhong, Synth. Commun.,
2001, 31, 245.
20. G. M. Sheldrick, SHELXTL v. 5.10, Structure Determination
Software Suite, Bruker AXS, Madison (Wisconsin,
USA), 1998.
13. Jpn Pat. 92ꢀ360826; Chem. Abstrs., 1994, 121, 134107.
14. W. R. Hatchard, J. Org. Chem., 1964, 29, 664.
15. E. A. Serebryakov and S. G. Zlotin, Izv. Akad. Nauk, Ser.
Khim., 2002, 1426 [Russ. Chem. Bull., Int. Ed., 2002, 51, 1549].
16. F. A. Kucherov and S. G. Zlotin, Izv. Akad. Nauk, Ser.
Khim., 2001, 1580 [Russ. Chem. Bull., Int. Ed., 2001,
50, 1657.a
Received January 6, 2004;
in revised form April 7, 2004