Regioselective replacement of nitro groups in 2,4,6-trinitrotoluene under the action of alkanethiols. Synthesis of ortho-(alkylthio)-substituted nitrotoluenes and their oxidation to sulfoxides and sulfones

Article abstract of DOI:10.1023/A:1009578201443

The reactions of 2,4,6-trinitrotoluene with alkanethiols in the presence of K₂CO₃ (the molar ratio of the reactants is 1 : 1 : 1) in dipolar aprotic solvents result in selective replacement of the ortho-nitro group to form 2-alkylthio-4,6-dinitrotoluenes, which can be oxidized to the corresponding sulfoxides or sulfones. The second ortho-nitro group can be replaced under the action of one more equivalent of alkanethiol on sulfides as exemplified in PhCH₂SH.

Full text of DOI:10.1023/A:1009578201443

Russian Chemical Bulletin, International Edition, Vol. 50, No. 2, pp. 261—264, February, 2001
261
Organic Chemistry
Regioselective replacement of nitro groups in 2,4,6-trinitrotoluene under
the action of alkanethiols. Synthesis of ortho-(alkylthio)-substituted
nitrotoluenes and their oxidation to sulfoxides and sulfones
O. V. Serushkina, M. D. Dutov, and S. A. Shevelev«
N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences,
47 Leninsky prosp., 117913 Moscow, Russian Federation.
Fax: +7 (095) 135 5328. E-mail: shevelev@cacr.ioc.ac.ru
The reactions of 2,4,6-trinitrotoluene with alkanethiols in the presence of K2CO3 (the
molar ratio of the reactants is 1 : 1 : 1) in dipolar aprotic solvents result in selective replacement
of the ortho-nitro group to form 2-alkylthio-4,6-dinitrotoluenes, which can be oxidized to the
corresponding sulfoxides or sulfones. The second ortho-nitro group can be replaced under the
action of one more equivalent of alkanethiol on sulfides as exemplified in PhCH2SH.
Key words: trinitrotoluene, alkanethiols, replacement of the nitro group.
Previously,1—4 we have demonstrated that benzene-
thiols replace a nitro group in 2,4,6-trinitrotoluene (TNT)
in dipolar aprotic solvents in the presence of alkali metal
carbonates, only the ortho-nitro group being replaced to
form sulfides. The latter can be selectively oxidized to
the corresponding sulfoxides or sulfones.
isomers. Only in the cases of 1c and 1e, the fraction of
the para isomer reaches 10% (1H NMR spectral data).
Single crystallization from the solvents listed in Table 1
is usually sufficient to remove the para isomer. Only in
the cases of sulfides 2c and 2e, double crystallization is
required.
We found that the reactions of TNT with various
alkanethiols 1 under analogous conditions (N-methyl-
pyrrolidone (N-MP) or DMF are the solvents of choice)
in the presence of solid K2CO3 (the molar ratio of the
reactants is 1 : 1 : 1) are also regioselective, viz., the
ortho-nitro group is primarily replaced to form the corre-
sponding 2-alkylthio-4,6-dinitrotoluenes 2 (Scheme 1,
Table 1).
It was shown that ortho-replacement is accompanied
by para-replacement which occurs to a small extent.
Generally, the fraction of the para isomer is no higher
than 5—6% of the total amount of the ortho and para
Under these conditions, the reactions proceed at
20 °C. However, in some cases it is more convenient to
carry out the reactions at 50 °C (see Table 1).
Using sulfide 2à as an example, it was demonstrated
that the second nitro group can also be replaced (under
the action of PhCH2SH + K2CO3), the ortho-nitro
group also being selectively replaced to form bis-sulfide
3 (see Scheme 1). The best results were obtained in
HMPA at ∼20 °C (see Table 1).
It should be noted that only one example of replace-
ment of the nitro group in TNT under the action of an
alkanethiol has been described previously. Thus the re-
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 2, pp. 252—254, February, 2001.
1066-5285/00/5002-261 $25.00 © 2001 Plenum Publishing Corporation

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Russ.Chem.Bull., Int.Ed., Vol. 50, No. 2, February, 2001
Serushkina et al.
Scheme 1
In several examples, we demonstrated that sulfides 2
can be selectively oxidized under the action of H2O2 +
AcOH to form either the corresponding sulfoxides or
sulfones depending on the reaction conditions. The
reactions with the use of a nearly equimolar amount of
H2O2 at ∼20 °C afforded sulfoxides 4, whereas the
reactions with the use of a large excess of H2O2 in
boiling AcOH gave rise to the corresponding sulfones 5
(Scheme 2, see Table 1). Earlier, we have used an
analogous procedure for the selective oxidation of the
replacement products of the ortho-nitro group in TNT
under the action of benzenethiols.1—4
Me
Me
O2N
NO2
+ RSH
O2N
SR
K2CO3
1
NO2
NO2
2a—j
Me
PhCH2S
SCH2Ph
PhCH2SH, K2CO3
(R = PhCH2—)
Scheme 2
NO2
3
Me
O
O2N
SR
R = PhCH2— (a);
CH2
(b); —CH2 —CH—Me (c);
Me
—CH2CHOHCH2OH (d);
(e); R´OOCCH2— (R´ = H (f),
i
ii
NO2
2a,c,g,h,j
Et (g), Me (h)); R″OOCCHMe (R″ = H (i), Et (j))
Me
Me
SOR
O2N
O2N
SO2R
Table 1. Reaction conditions, melting points, and yields of
ortho-S-alkylthio-substituted nitrotoluenes
Com- Reaction conditions Yield*
M.p./°C
(solvent)
NO2
NO2
pound
(%)
4c,g
T/°Ñ
t/h
5a,c,g,h,j
2a
2b
2c
2d
2e
2f
2g
2h
2i
50
50
20
20
20
20
20
20
20
20
20
20
20
118**
118**
118**
118**
118**
3
2
11
5
68
81
58
55
27
37
59
88
43
86
36
84
60
94
83
45
77
13
111—112 (MeCN)
51—52 (EtOH)
98—99 (CCl4/CHCl3)
109—110 (H2O)
99—100 (CCl4/CHCl3)
137—138 (EtOH)
73—74 (EtOH)
70—71 (EtOH)
138—139
31—32 (EtOH)
141—142 (MeCN)
116—117 (CCl4)
21—22
Regents and conditions. i. from 2c,g; 20 °C, the molar ratio
2 : H2O2 ≈ 1 : 1.
ii. from 2a,c,g,h,j; 118 °C, nearly fourfold molar excess of H2O2.
18
18
18
24
48
24
280
53
20
0.5
0.5
3
Thus, we developed a procedure for the preparation
of 2-alkylthio-, 2-alkylsulfinyl-, and 2-alkylsulfonyl-4,6-
dinitrotoluenes.
The structures of the resulting compounds were estab-
1
2j
lished by H NMR spectroscopy (Table 2), mass spec-
3
trometry in the electron impact mode (in all cases, except
for sulfones 5à, 5d, and 5h, the formation of molecular
ions was observed), and IR spectroscopy (νas (N O2),
4c
4g
5a
5c
5g
5h
5j
167—168
107—108
107—108 (AcOH/H2O)
113—114 (AcOH/H2O)
123—124 (MeOH)
–1
–1
1550—1580 cm ; νs, 1350—1380 (NO2) cm ; ν (SO),
–1
–1
1070—1030 cm ; νas (SO2), 1300—1340 cm ; νs (SO2),
–1
1120—1160 cm ) and were confirmed by the data from
1
3.5
elemental analysis (see Table 2).
* With respect to the individual product isolated.
** Boiling AcOH.
Experimental
The melting points were determined on a Boetius stage (the
rate of heating was 4 deg min–1). The IR spectra were recorded
on a Specord M-80 spectrometer in KBr pellets. The mass
spectra were obtained on an MS-30 spectrometer (Kratos). The
action with the EtSH—LiOH system in HMPA led
primarily to ortho replacement.5 We demonstrated that
the approach proposed in the present study is more
efficient. Thus the yield of sulfide 2à prepared according
to our procedure was 68%, whereas under conditions of
the cited work5 it was 40%. The yields of bis-sulfide 3
were 36 and 9%, respectively. Analogous results were
obtained in other cases as well.
course of the reactions was monitored by HPLC on
a
Liquochrom (Model 2010) instrument on column with
a
Silasorb-18 as the reversed phase using the 3 : 1 MeCN—H2O
system as the eluent. The 1H NMR spectra were recorded on a
Bruker AC-200 spectrometer.

Synthesis of (o-alkylthio)nitrotoluenes
Russ.Chem.Bull., Int.Ed., Vol. 50, No. 2, February, 2001
263
Table 2. 1H NMR spectra and data of elemental analysis of ortho-substituted nitrotoluenes
Com-
pound
Found
Calculated
Molecular
formula
1H NMR (solvent; δ, J/Hz)
(%)
C
H
N
S
2à
2b
55.07
55.26
48.92
48.98
3.73
3.97
3.41
3.42
9.33
9.21
9.61
9.52
10.71
10.53
10.94
10.89
C14H12N2O4S
C12H10N2O5S
Acetone-d6; 2.51 (s, 3 H); 4.51 (s, 2 H); 7.32 (m, 3 H);
7.47 (m, 2 H); 8.38 (d, 1 H, J = 2); 8.42 (d, 1 H, J = 2)
CDCl3; 2.54 (s, 3 H); 4.29 (s, 2 H); 6.26 (dd, 1 H,
J = 3, 1.5); 6.33 (d, 1 H, J = 3); 7.37 (d, 1 H, J = 1.5);
8.37 (d, 1 H, J = 2); 8.42 (d, 1 H, J = 2)
2c
2d
2e
48.59
48.88
5.08
5.22
10.48
10.36
11.98
11.86
C11H14N2O4S
C10H12N2O6S
C13H16N2O4S
CDCl3; 1.15 (d, 6 H, J = 10); 2.04 (nonet, 1 H, J = 10);
2.58 (s, 3 H); 2.88 (d, 2 H, J = 11); 8.21 (d, 1 H, J = 2);
8.34 (d, 1 H, J = 2)
41.45
41.67
4.09
4.20
9.81
9.72
11.22
11.12
Acetone-d6; 2.53 (s, 3 H); 3.27 (dd, 1 H, J = 14, 8);
3.48 (dd, 1 H, J = 14, 6); 3.66 (t, 2 H, J = 10); 3.96 (m, 2 H);
4.38 (d, 1 H, J = 8); 8.40 (d, 1 H, J = 2); 8.52 (d, 1 H, J = 2)
Acetone-d6; 1.49 (m, 6 H); 1.65 (m, 2 H); 1.79 (m, 2 H);
2.56 (s, 3 H); 3.51 (m, 1 H); 8.40 (d, 1 H, J = 2);
8.45 (d, 1 H, J = 2)
52.55
52.69
5.38
5.44
9.51
9.45
10.89
10.82
2f
2g
2h
2i
39.61
39.71
43.89
44.00
41.91
41.96
41.82
41.96
45.69
45.86
2.89
2.96
3.97
4.03
3.49
3.52
3.36
3.52
4.33
4.49
10.35
10.29
9.50
9.33
9.80
9.79
9.91
9.79
9.08
8.91
11.87
11.78
10.71
10.68
11.22
11.20
11.29
11.20
10.32
10.20
C9H8N2O6S
Acetone-d6; 2.51 (s, 3 H); 4.13 (s, 2 H); 8.47 (d, 1 H, J = 2);
8.52 (d, 1 H, J = 2)
Acetone-d6; 1.22 (t, 3 H, J = 9); 2.56 (s, 3 H); 4.12 (s, 2 H);
4.18 (q, 2 H, J = 10); 8.44 (d, 1 H, J = 2); 8.48 (d, 1 H, J = 2)
DMSO-d6; 2.44 (s, 3 H); 3.66 (s, 3 H); 4.28 (s, 2 H);
8.31 (d, 1 H, J = 2); 8.51 (d, 1 H, J = 2)
Acetone-d6; 1.61 (d, 3 H, J = 10); 2.64 (s, 3 H);
4.29 (q, 1 H, J = 9); 8.55 (d, 1 H, J = 2); 8.68 (d, 1 H, J = 2)
CDCl3; 1.25 (t, 3 H, J = 9); 1.65 (d, 3 H, J = 10);
2.63 (s, 3 H); 4.00 (q, 1 H, J = 9); 4.20 (q, 2 H, J = 9);
8.45 (d, 1 H, J = 2); 8.54 (d, 1 H, J = 2)
C11H12N2O6S
C10H10N2O6S
C10H10N2O6S
C12H14N2O6S
2j
3
65.98
66.11
46.03
46.15
4.96
5.02
4.79
4.93
3.72
3.67
9.81
9.78
16.91
16.81
11.29
11.20
C21H19NO2S2
C11H14N2O5S
DMSO-d6; 2.33 (s, 3 H); 4.34 (s, 4 H); 7.32 (m, 10 H);
7.91 (s, 2 H)
CDCl3; 1.14 (d, 3 H, J = 9); 1.26 (d, 3 H, J = 9);
2.42 (nonet, 1 H, J = 6); 2.61 (s, 3 H); 2.79—2.55 (m, 2 H);
8.80 (d, 1 H, J = 2); 9.08 (d, 1 H, J = 2)
4c
4g
41.63
41.77
3.74
3.82
8.98
8.86
10.22
10.14
C11H12N2O7S
Acetone-d6; 1.20 (t, 3 H, J = 9); 2.67 (s, 3 H); 3.88 (d, 1 H,
J = 18); 4.17 (q, 2 H, J = 10); 4.28 (d, 1 H, J = 18);
8.88 (d, 1 H, J = 2); 8.92 (d, 1 H, J = 2)
5a
5c
49.89
50.00
43.59
43.71
3.53
3.60
4.57
4.67
8.47
8.33
9.33
9.27
9.71
9.53
10.81
10.61
C14H12N2O6S
C11H14N2O6S
Acetone-d6; 2.68 (s, 3 H); 4.80 (s, 2 H); 7.32 (m, 5 H);
8.72 (d, 1 H, J = 2); 8.90 (d, 1 H, J = 2)
CDCl3; 1.15 (d, 6 H, J = 9); 2.42 (nonet, 1 H, J = 10);
2.92 (s, 3 H); 3.15 (d, 2 H, J = 9); 8.70 (d, 1 H, J = 2);
9.12 (d, 1 H, J = 2)
5g
39.78
39.76
3.52
3.64
8.59
8.43
9.33
9.65
C11H12N2O8S
Acetone-d6; 1.14 (t, 3 H, J = 10); 2.93 (s, 3 H);
4.12 (q, 2 H, J = 10); 4.74 (s, 2 H); 9.00 (d, 1 H, J = 2);
9.04 (d, 1 H, J = 2)
5h
5j
37.69
37.74
41.49
41.62
3.09
3.17
4.01
4.07
8.87
8.80
8.13
8.09
10.12
10.07
9.33
C10H10N2O8S
C12H11N2O8S
CDCl3; 2.92 (s, 3 H); 3.73 (s, 3 H); 4.32 (s, 2 H);
8.84 (d, 1 H, J = 2); 9.11 (d, 1 H, J = 2)
Acetone-d6; 1.08 (t, 3 H, J = 9); 1.68 (d, 3 H, J = 10);
2.91 (s, 3 H); 4.08 (q, 2 H, J = 10); 4.76 (q, 1 H, J = 9);
8.96 (d, 1 H, J = 2); 9.05 (d, 1 H, J = 2)
9.26
2-Alkylthio-4,6-dinitrotoluenes (2à—j). A solution of TNT
(5.675 g, 0.025 mol) in N-MP (10 mL) was added to a mixture
of the corresponding alkanethiol (0.025 mol), K2CO3 (3.45 g,
0.025 mol), and N-MP (15 mL). The reaction mixture was
stirred under conditions given in Table 1. Then the mixture was
poured into cold water (120 mL). The precipitate that formed
was filtered off, dried, and recrystallized from the corresponding
solvent (see Table 1). Compounds 2à, 2b, 2g, 2h, and 2j were
dissolved in chloroform and filtered through a silica gel layer
(∼20 g) before recrystallization. In the cases of compounds 2f
and 2i, the reaction mixtures were poured into CH2Cl2 (120 mL).
The precipitates that formed were filtered off, dried, and dis-
solved in water and the solution were filtered. The filtrates were
acidified with HCl and the precipitates that formed were filtered
off and recrystallized.
2,6-Bis(benzylthio)-4-nitrotoluene (3). A mixture of com-
pound 2à (6.08 g, 0.02 mol), HMPA (20 mL), PhCH2SH
(2.48 g, 0.02 mol), and K2CO3 (2.76 g, 0.02 mol) was stirred at

264
Russ.Chem.Bull., Int.Ed., Vol. 50, No. 2, February, 2001
Serushkina et al.
∼20 °C for 12 days. Then the mixture was poured into cold
water (100 mL) and the precipitate that formed was filtered off,
dried, and recrystallized.
References
Sulfoxides 4c and 4g. A mixture of sulfide 2c or 2g
(0.025 mol), 35% H2O2 (2.25 mL), and glacial AcOH (45 mL)
was stirred at ∼20 °C over a period indicated in Table 1. Then
the mixture was poured into cold water (225 mL) and the
precipitate that formed was filtered off and dried (compound 4c
was recrystallized).
1. S. A. Shevelev, M. D. Dutov, and O. V. Serushkina, Izv.
Akad. Nauk, Ser. Khim., 1995, 2528 [Russ. Chem. Bull., 1995,
44, 2424 (Engl. Transl.)].
2. M. D. Dutov and S. A. Shevelev, 9th International Congress
on Pesticide Chemistry, Book of Abstracts, Vol. 1, Paper
1A-037, London, UK, 1998.
Sulfones 5a, 5c, 5g, 5h, and 5j. A mixture of sulfide 2
(0.03 mol), 35% H2O2 (10.2 mL), and glacial AcOH (70 mL)
was refluxed over a period given in Table 1. Then the mixture
was cooled. In the case of sulfone 5h, the precipitate was
filtered off, dried, and recrystallized. In the cases of sulfones 5g
and 5j, the reaction mixtures were poured into cold water
(350 mL) and the precipitates that formed were filtered off,
dried, and recrystallized. In the case of sulfone 5j, the precipi-
tate was stirred in a dilute aqueous solution of KOH for 4 h
before recrystallization.
3. S. A. Shevelev, M. D. Dutov, and O. V. Serushkinà, Abstracts
of Papers, V Intern. Conf. on Chemical High Technology,
Yaroslavl', Russia, May, 1998, 122.
4. S. A. Shevelev, M. D. Dutov, O. V. Serushkina, and O. Yu.
Sapozhnikov, 18th International Symposium on the Organic
Chemistry of Sulfur, Abstracts of Papers, P-91, Florence,
Italy, 1998, p. 189.
5. F. Benedetti, D. R. Marshall, Ch. J. M. Stirling, and J. L.
Leng, J. Chem. Soc., Chem. Commun., 1982, 918.
This work was financially supported by the Interna-
tional Science and Technology Center (ISTC) (Project
No. 419).
Received May 25, 2000;
in revised form September 4, 2000