Synthetic utilization of polynitroaromatic compounds. 1. S-derivatization of 1-substituted 2,4,6-trinitrobenzenes with thiols

Article abstract of DOI:10.1021/jo000479d

Reactions of 1-R-2,4,6-trinitrobenenes (R = alkyl, protected aldehyde, aminocarbonyl, cyano groups, or isoxazole ring) with thiol salts were investigated. In most cases, these reactions gave a mixture of minor para and major ortho substitution products. Reactions of N,N-disubstituted 2,4,6-trinitrobenzamides with S-,O-, and N-nucleophiles afforded products of substitution of the p-nitro group exclusively. 1-Cyano-2,4,6-trinitrobenzene was found to be the most reactive and the least selective: all three nitro groups can be substituted using an excess of thiol salts. 2-R-4,6-dinitrobenzamides showed no regioselectivity under similar conditions to yield 1:1 mixtures of para and ortho isomers.

Full text of DOI:10.1021/jo000479d

8430
J . Org. Chem. 2000, 65, 8430-8438
Syn th etic Utiliza tion of P olyn itr oa r om a tic Com p ou n d s. 1.
S-Der iva tiza tion of 1-Su bstitu ted 2,4,6-Tr in itr oben zen es w ith
Th iols
S. G. Zlotin,* P. G. Kislitsin, A. V. Samet, E. A. Serebryakov, L. D. Konyushkin, and
V. V. Semenov
N. D. Zelinsky Institute of Organic Chemistry RAS, Leninsky Pr., 47 Moscow, 117913, Russia
A. C. Buchanan III and A. A. Gakh*
Chemical and Analytical Sciences Division, Oak Ridge National Laboratory,
Oak Ridge, Tennessee 37831-6197
gakhaa@ornl.gov
Received March 29, 2000
Reactions of 1-R-2,4,6-trinitrobenenes (R ) alkyl, protected aldehyde, aminocarbonyl, cyano groups,
or isoxazole ring) with thiol salts were investigated. In most cases, these reactions gave a mixture
of minor para and major ortho substitution products. Reactions of N,N-disubstituted 2,4,6-
trinitrobenzamides with S-,O-, and N-nucleophiles afforded products of substitution of the p-nitro
group exclusively. 1-Cyano-2,4,6-trinitrobenzene was found to be the most reactive and the least
selective: all three nitro groups can be substituted using an excess of thiol salts. 2-R-4,6-di-
nitrobenzamides showed no regioselectivity under similar conditions to yield 1:1 mixtures of para
and ortho isomers.
In tr od u ction
For our purposes, we needed 2-alkyl(aryl)thio-4,6-
dinitrobenzene derivatives containing methyl, carbami-
domethyl, carbonyl, aminocarbonyl, and cyano groups as
well as an isoxazole ring at position 1 of the benzene ring.
A direct approach to the desired compounds includes
reactions of TNT, 2,4,6-trinitrobenzaldehyde, 2,4,6-trini-
trobenzamides, 2,4,6-trinitrophenylacetanilides, and 2,4,6-
trinitrobenzonitrile as well as 4-picrylisoxazole with the
appropriate alkyl(aryl)thiols and their salts. All these
starting compounds can be synthesized from readily
available TNT, and this methodology may be considered
as one of the approaches to its synthetic utilization.
To the best of our knowledge, regioselectivity of reac-
tions of these 1-substituted 2,4,6-trinitrobenzenes with
various nucleophiles has not been systematically inves-
tigated.7,8 Therefore, it was difficult to predict a priori
how the electronic and steric nature of substituents at
position 1 of the benzene ring and substituents in the
thiol component would effect reactivity and regioselec-
tivity of the reactions.
Besides their obvious industrial (bulk intermediates,
such as 2,4-dinitrotoluene) and military use (explosives,
such as 2,4,6-trinitrotoluene (TNT)), polynitroaromatic
compounds have attracted attention as possible starting
materials for synthesis of biologically active compounds
(including fused sulfur-containing heterocycles).1 Syn-
thetic utilization of 1-R-2,4,6-trinitroaromatic compounds
in this case can be started with nucleophilic substitution
of nitro groups by thiolate anions.2-8 We investigated
these reactions in more detail to develop optimal proce-
dures for such transformations.
Resu lts a n d Discu ssion
Although reactions of nitro- and dinitroaromatics with
S-nucleophiles have been reported previously (see, for
example, refs 2-8), only a few synthetically useful trans-
formations of trinitroaromatics were investigated. It is
known that 2,4,6-trinitrotoluene (TNT) reacts with lithium
ethylmercaptide7 and with thiophenol8 in the presence
of K2CO3 to give 2-ethylthio- and 2-phenylthio-4,6-dini-
trotoluene, respectively. Only traces (∼1%) of isomeric
2,6-dinitro-4-ethylthiotoluene have been identified in the
former reaction,7 and no information about formation of
2,6-dinitro-4-(phenylthio)toluene has been reported for
the latter.8
The starting 2,4,6-trinitrobenzalazine (1) was synthe-
sized by reaction of TNT with p-dimethylaminonitrosoben-
zene.9,10 4-Picrylisoxazole (5) was prepared from TNT by
a modified literature procedure.11 The compound 5 as well
as intermediatespicrylmalonaldehyde (4)shave been
1
fully characterized by H NMR spectra (Scheme 1).
2,4,6-Trinitrobenzoic and 2,4,6-trinitrophenylacetic
acids, as well as their functional derivatives (such as
amides and nitriles), offer additional opportunities as
starting materials for synthesis of useful polysubstituted
aromatic compounds. It is known that 2,4,6-trinitroben-
zoic and 2,4,6-trinitrophenylacetic acids can be prepared
by oxidation of TNT and â-(2,4,6-trinitrophenyl)ethyl
(1) Lobry de Bruyn, C. A.; Blanksma, J . J . Rec. Trav. Chim. 1901,
20, 115.
(2) Friedlander, P. Chem. Ber. 1906, 39, 1065.
(3) Beck, J . R. J . Org. Chem. 1972, 37, 3224.
(4) Beck, J . R. J . Org. Chem. 1973, 38, 4086.
(5) Beck, J . R.; Yahner, J . A. J . Org. Chem. 1974, 39, 3440.
(6) Kornblum, N.; Cheng, L.; Kerber, R. C.; Kestner, M. M.; Newton,
B. N.; Pinnick, H. W.; Smith, R. G.; Wade, P. A. J . Org. Chem. 1976,
41(9), 1560.
(7) Benedetty, F.; Marshall, D. R.; Stirling, C. J . M.; Leng, J . L.
Chem. Commun. 1982, 918.
(8) Shevelev, S. A.; Dutov, M. D.; Serushkina, O. V. Russ. Chem.
Bull. 1995, 44, 2424.
(9) Sach, F.; Kempf, R. Chem. Ber. 1902, 35, 1224.
(10) Secareanu, St. Chem. Ber. 1931, 64, 834.
(11) Zbarsky, V. L.; Shutov, G. M.; Gilin, V. F.; Orlova, E. Yu. Z.
Org. Khim. (Russ.) 1968, 4, 1970.
10.1021/jo000479d CCC: $19.00 © 2000 American Chemical Society
Published on Web 11/10/2000

Synthetic Utilization of Polynitroaromatic Compounds
J . Org. Chem., Vol. 65, No. 25, 2000 8431
Ta ble 1. Rea ction Con d ition s a n d Yield s of
2,4,6-tr in itr oben za m id es 7-18 in Rea ction s of
2,4,6-Tr in itr oben zoyl Ch lor id e w ith Am in es (Meth od A)
Sch em e 1
T
time yield
compd
R1
R2
solvent (°C) (h) (%)
7
8
9
H
H
H
H
H
H
H
H
H
H
Et
H
CH3
C(CH3)3
CH2Ph
PhH/H2O
PhH/H2O
PhH
PhH
PhH
PhH
PhH
PhH
PhH
5
5
2
2
6
2
2
5
5
3
5
5
5
5
54
76
56
60
79
69
62
73
66
49
84
61
20
20
20
15
40
20
15
15
15
15
10
11
12
13
14
15
16
17
18
Ph
C6H4Br(p-)
C6H4CO2Et(o-)
C6H4CO2H(m-)
C6H4OCF3(p-)
C6H4OCClF2(p-) PhH
Et PhH
R1, R2 ) -(CH2)2O(CH2)2- PhH
(method B). The method afforded the amide 7 in much
higher yield (90%) than the reaction of 2,4,6-trinitroben-
zoic acid chloride with NH3 (54%). It also eliminated the
need for preparation of the intermediate acid chloride 6,
and appears to be an attractive method for large-scale
preparation of the target compound 7.
The anilide of 2,4,6-trinitrophenylacetic acid (19)
(Scheme 4) has been synthesized by a sequence of reac-
tions including reaction of 2,4,6-trinitrophenylacetic acid
with SOCl2 followed by reaction of 2,4,6-trinitrophenyl-
acetyl chloride with aniline. It is worth mentioning that
the acid chloride was used in the reaction without
isolation and purification because of its rapid hydrolysis
on air.
acetate with Na2Cr2O7 and CrO3,13 respectively. Envi-
12
ronmentally benign and efficient technology for prepara-
tion of 2,4,6-trinitrobenzoic acid by oxidation of TNT with
nitric acid has been recently developed. [This tecnology
has been developed specifically for this project at “SKTB
Technolog” (St. Petersburg, Russia) using pilot-scale
facilities to produce multikilogram samples of 2,4,6-
trinitrobenzoic acid. See also A. A. Astrat′ev et al.
Production of 2,4,6-trinitrobenzoic acid, ORNL Report
ORNL/TM-2000/117, May 2000.] We have also shown
that 2,4,6-trinitrophenylacetic acid can be easily synthe-
sized by direct oxidation of â-(2,4,6-trinitrophenyl)ethanol
(prepared from TNT and CH2O)13 with CrO3 (Scheme 2).
Sch em e 4
Sch em e 2
2,4,6-Trinitrobenzoic acid was converted to a series of
2,4,6-trinitrobenzamides (7-18) by a sequence of syn-
thetic procedures starting with acid chloride synthesis
(SOCl2) followed by reactions of 2,4,6-trinitrobenzoic acid
chloride (6) with the appropriate amines (method A).
Reactions of the acid chloride (6) with ammonia and
methylamine were carried out in a 2-phase benzene-
water mixture, and with benzylamine and arylamines in
benzene. Two molar equivalents of amine or an equimolar
mixture of amine and Et3N (in the case of the compounds
15 and 16) were used in reactions. Yields of the amides
7-18 calculated based on the 2,4,6-trinitrobenzoic acid
chloride (6) were 54-84% (Table 1, Scheme 3).
We have shown that 2,4,6-trinitrotoluene reacted with
4-methylthiophenol, 3-bromo-6-fluorothiophenol, ben-
zylmercaptan and R-mercaptomethyl acetate in the same
selective manner as with unsubstituted alkyl(aryl)thi-
ols7,8 to give the appropriate 2-aryl(alkyl)thio-4,6-dini-
1
trotoluenes (20-23, Scheme 5). According to H NMR
spectra, only compound 23 was contaminated with small
amount (∼7%) of the appropriate para-benzylthioderiva-
tive 23a . The reactions were carried out in DMF or
DMSO (in previous publications HMPTA and lactams
were used as solvents for nucleophilic substitution reac-
tions of TNT)7,8 in the presence of metal hydroxides
(LiOH or KOH) or K2CO3. The reaction conditions and
yields of the compounds 20-23 are given in Table 2.
Sch em e 3
Sch em e 5
2,4,6-Trinitrobenzamide (7) has been alternatively
synthesized by the reaction of 2,4,6-trinitrobenzoic acid
with urea in fuming H2SO4 containing 30% of SO3
(12) Syntezy Org. Preparatov (Russ.) 1949, 1, 416.
(13) Bonecki, Z.; Urbanski, T. Bull. Acad. Pol. Sci. 1961, 9(7), 461.

8432 J . Org. Chem., Vol. 65, No. 25, 2000
Zlotin et al.
Ta ble 2. Rea ction Con d ition s a n d Yield s of
2-Th io-Su bstitu ted 4,6-Din itr otolu en es 20-23 in
Rea ction s of 2,4,6-Tr in itr otolu en e (TNT) w ith Th iols
NMR spectra of the ortho isomers and only one signal in
the 1H NMR spectrum of the para isomer. The structures
of para-substituted compounds 38b-40b were also con-
firmed by 13C NMR spectra containing only four signals
of nitroaromatic carbons.
T
time, yield,
compd
20
R
solvent base (°C)
h
%
-C6H4CH3(-p)
-C6H4CH3(-p)
-C6H3-5-Br-2-F DMF
-C6H3-5-Br-2-F DMSO KOH
-CH2CO2CH3 DMF
DMSO K2CO3 40
DMSO LiOH
DMSO KOH
15
15
15
15
10
10
10
10
4
42
70
58
20
44
40
The major difference in reactivity of N-(un)substituted
and N,N-disubstituted 2,4,6-trinitrobenzamides can also
be seen in the reactions of amides with O-nucleophiles.
Thus, N-phenyl-2,4,6-trinitrobenzamide (11) reacts with
methylate and phenolate anions (prepared in situ from
the alcohols and K2CO3 in DMF)14 to give ortho ethers
41a and 42a as the only products in 70-83% yields.
20
21
21
22
KOH
K2CO3 50
23 + ∼7% -CH2Ph
1
23a
1
Schiff bases of 2,4,6-trinitrobenzaldehyde (1), 4-picryl-
isoxazole (5), and 2,4,6-trinitrophenylacetic acid anilide
(19) showed the same regioselectivity in reactions with
thiophenols. The only isolated products of the reactions
were N-[2′,4′-dinitro-6′-(phenylthio)benzyliden]-4-dimeth-
ylaminoaniline (24), 4-[2,4-dinitro-6-(p-tolylthio)phenyl]-
isoxazole (25), and (2-benzylthio-4,6-dinitrophenyl)acetic
acid anilide (26) (Scheme 6). Yields of the compounds 24-
26 were 21-52% (Table 3).
Signals of aromatic protons Ha and Hb in H NMR spectra
of the compounds 41a and 42a have different chemical
shifts (8.28 and 8.50 for 41a and 7.92 and 8.65 ppm for
42a ), a strong evidence of ortho location of -OR groups
in these compounds. No para isomers were found in the
reaction mixtures (Scheme 8).
Sch em e 8
Acid hydrolysis of the compound 24 gave 2,4-dinitro-
6-(phenylthio)benzaldehyde (27) in 46% yield (Scheme 6).
Sch em e 6
On the other hand, reactions of 2,4,6-trinitrobenzoic
acid morpholide (18) with the same O-nucleophiles, as
well as with NaN3, in the similar conditions afforded
exclusively para-substituted ethers 43b, 44b and azide
45b, respectively, in yields 83%, 94%, and 48% (Scheme
The structure of compounds 20-27 as o-aryl(alkyl)-
thio derivatives has been unequivocally established on
the basis of 1H NMR spectra containing two unequivalent
signals of aromatic protons at 7.8-9.1 ppm.
1
9). H NMR spectra of the raw reaction mixture showed
no traces of the appropriate ortho isomers. The structures
of compounds 43b-45b as para-substituted 2,6-dini-
Unexpected results were obtained during investigation
of reactions of 2,4,6-trinitrobenzamides with nucleophiles.
We observed that the regioselectivity of these reactions
depends on the structure of the amides. Thus, 2,4,6-
trinitrobenzamides (7-12, 15, and 16) containing at least
one hydrogen atom at nitrogen atom of the amido group
reacted with thiols with relatively high ortho regioselec-
tivity. These reactions typically gave mixtures of o- and
p-benzylthio- derivatives 28a -37a and 28b-37b con-
taining, according to 1H NMR spectra, ∼90% of the ortho
isomer 28a -37a (Scheme 7). On the other hand, N,N-
disubstituted 2,4,6-trinitrobenzamides 17 and 18 reacted
with thiols in regiospecific manner to afford products of
substitution of the p-nitro group 38b-40b exclusively.
No traces of the isomeric 2-alkylthio-4,6-dinitrobenz-
amides (38a -40a ) were found in the reaction mixtures
(Table 4).
1
trobenzoic acid derivatives have been confirmed by H
NMR and 13C spectra showing the presence two equiva-
lent hydrogen atoms and four different carbon atoms of
the nitrobenzene ring.
Sch em e 9
It appears that the observed regioselectivity is probably
limited to only compounds with three nitro groups.
Similar reactions of 2-substituted 4,6-dinitrobenzamides
(where the 2-substituent is not a nitro group) show little
or no regioselectivity. Thus, reaction of the compound 42a
with benzylmercaptan in the presence of K2CO3 gave a
mixture (∼1:1) of isomeric thioethers 46a and 46b in 75%
total yield (Scheme 10).
Sch em e 7
(14) Shevelev, S. A.; Dutov, M. D.; Serushkina, O. V.; Korolev, M.
A.; Rusanov, A. L. Russ. Chem. Bull. 1995, 44, 384.
(15) Konarsky, J .; Graczyk, A. Rocz. Chem. 1972, 46, 745.
(16) Rheingold, A. L.; Baldacchini, C. J .; Grote, C. W. J . Cryst.
Spectrosc. Research 1989, 19(1), 25.
Structures of the isomers “a ” and “b” as 2-alkylthio and
4-alkylthio derivatives, respectively, were assigned based
1
on the presence of two signals of aromatic protons in H

Synthetic Utilization of Polynitroaromatic Compounds
J . Org. Chem., Vol. 65, No. 25, 2000 8433
Ta ble 3. Rea ction Con d ition s a n d Yield s of 2-Th io-Su bstitu ted 1-R-4,6-d in itr oben zen es 24-26 in Rea ction s of
1-R-2,4,6-tr in itr oben zen es w ith Th iols
compd
R
R′
solvent
base
T (oC)
time (h)
yield (%)
24
25
CHdNC6H4N(Me)2(-p)
Ph
EtOH
DMSO
KOH
K2CO3
15
15
10
2
21
52
C6H4CH3(-p)
26
CH2CONHPh
CH2Ph
DMF
K2CO3
15
4
46
Sch em e 10
Sch em e 12
Similarly, reaction of 2-benzylsulfonyl-4,6-dinitroben-
zamide (47) (prepared by oxidation of the appropriate
sulfide 28a with H2O2) with benzylthiol afforded an
equimolar mixture of 2- and 4-benzylthio derivatives 48a
and 48b in 78% total yield (Scheme 11).
Sch em e 11
Ta ble 4. Ra tios a n d Tota l Yield s of
2-Alk ylth io-4,6-d in itr oben za m id es 28a -37a a n d
4-Alk ylth io-2,6-d in itr oben za m id es 28b-37b in Rea ction s
of 2,4,6-Tr in itr oben za m id es 7-12 a n d 15-18 w ith Th iols
starting
compd
products
(ratio)
total
yield,%
R
H
R1
R2
7
7
H
CH2Ph
(28a ):(28b)
(∼10:1)
83
76
75
62
72
85
90
84
65
59
H
H
H
H
H
H
H
H
H
H
CH2CO2Me (29a :29b)
(∼10:1)
7
H
CH3
(30a :30b)
(∼10:1)
8
CH3
CH2Ph
CH2Ph
CH2Ph
CH2Ph
CH2Ph
CH2Ph
(31a :31b)
(∼10:1)
9
C(CH3)3
CH2Ph
(32a :32b)
(∼10:1)
10
11
12
15
16
(33a :33b)
(∼10:1)
Replacement of the amido group at position 1 of 2,4,6-
trinitrobenzamides by a cyano group also resulted in a
loss of regioselectivity of nucleophilic substitution reac-
tion. We found that 1-cyano-2,4,6-trinitrobenzene15 re-
acted with one molar equivalent of benzylmercaptan to
afford a mixture of o- and p-benzylthio derivatives 49a
and 49b in 3:1 proportion. Total yield of the mixture was
91%.
Ph
(34a :34b)
(∼10:1)
C6H4Br(-p)
C6H4OCF3(-p)
(35a :35b)
(∼10:1)
(36a :36b)
(∼10:1)
C6H4OCF2Cl(-p) CH2Ph
(37a :37b)
(∼10:1)
17
18
Et Et
CH2Ph
CH2Ph
(38b)a
85
88
R,R1
(CH2)2O(CH2)2
R,R1
(CH2)2O(CH2)2
)
(39b)a
Generally, 1-cyano-2,4,6-trinitrobenzene is more reac-
tive toward thiols than 2,4,6-trinitrobenzamides (7-12,
15-18). Three-fold molar excess of benzylmercaptan or
methyl R-mercaptoacetate gave compounds 50 and 51,
respectively, in which all three nitro groups were sub-
stituted by thio groups (Scheme 12). Compound 50
was also obtained when a mixture of o- and p-benzyl-
thio derivatives 49a and 49b (3:1) was treated with 2
molar equiv of benzylmercaptan under the same condi-
tions.
These results show that the nature of the substituents
in the benzene ring and the number of nitro groups in
polynitroaromatic compounds have significant influence
on the regioselectivity of the substitution reactions.
1-Substituted 2,4,6-trinitrobenzenes (TNT, 1, 5, 7-16,
and 19), containing alkyl, protected aldehyde, (un)sub-
stituted aminocarbonyl groups, or a heterocycle at posi-
tion 1 react predominantly at the ortho position rather
than at the para position. Reactions of N,N-disubstituted
18
)
CH2CO2Me (40b)a
76
a
No 2-alkylthio-4,6-dinitrobenzamides (38a -40a ) were found
in the reaction mixtures.
2,4,6-trinitrobenzamides (17 and 18) with S-, O-, and
N-nucleophiles under the same conditions afforded ex-
clusively products of para substitution. Finally, reactions
of 1-cyano-2,4,6-trinitrobenzene and 2-R-4,6-dinitroben-
zamides (42a , 47) (R * NO2) with thiols show little or
no regioselectivity.
It is known that o-nitro groups in TNT7 and 2,4,6-
trinitrobenzamide16 are oriented out of the plane of
aromatic ring due to steric interaction with those sub-
stituents. Most likely the same distortion exists in
1-substituted 2,4,6-trinitro aromatics (1) and (5), contain-
ing a protected aldehyde group or a heterocycle at the
position 1. Taking into account the geometry of the

8434 J . Org. Chem., Vol. 65, No. 25, 2000
Zlotin et al.
molecules, the preferential ortho substitution can be
explained by assuming that formation of a transition
state with a nucleophile at the ortho position should
require less perturbation than at the para position, and
should be energetically favorable (see also ref 19). This
explanation of ortho selectivity has been proposed earlier
for reactions of TNT with alkylthiols.7
Exp er im en ta l Section
Ca u tion : Polynitroaromatic compounds are potential ex-
plosives. Proper protective measures (shields, glasses) should
be used during experiments with these materials. Scale-up of
the reported reactions requires appropriate chemical hazards
testing.
(3-Dim et h yla m in o-2-p icr ylp r op -2-en ylid en e)d im et h -
ylim m on iu m Nitr a te (2). To a solution of TNT (2.27 g, 10
mmol) in absolute DMF (10 mL) was added freshly distilled
POCl3 (3 mL). The reaction mixture was heated at 80 °C for 4
h and then poured into crashed ice (∼40 g). The brownish-
orange precipitate was filtered off and then suspended in 60%
HNO3 (8 mL). The suspension was stirred for 40 min, the solid
was filtered off and recrystallized twice from EtOH to afford
1.80 g (45%) of 2, orange crystals: mp 215-220 °C [lit.11 mp
201-203 °C].
3-Dim eth ylam in o-2-picr ylacr olein (3). (3-Dimethylamino-
2-picrylprop-2-enylidene)dimethylimmonium nitrate (2) (1.80
g, 4.51 mmol) was dissolved in water (18 mL) at 80 °C and to
this solution 8.5% aqueous KOH solution (3.2 mL) was added
dropwise with stirring. A red oily substance precipitated from
the reaction mixture. It crystallized spontaneously after 30 min
(temperature of reaction mixture was kept at 80 °C). The
precipitate was filtered off, air-dried to afford 1.20 g (85%) of
3, red crystals: mp 178-180 °C [lit.11 mp 179.5-180.5 °C].
P icr ylm alon aldeh yde (3-Hydr oxy-2-picr ylacr olein ) (4).
To a suspension of 3-(dimethylamino)-2-picrylacrolein (3) (1.20
g, 3.87 mmol) in water (50 mL) was added 8.5% aqueous KOH
solution (6 mL), and the mixture was refluxed for 2 h. It was
then cooled to 20 °C, and 35% HCl (3 mL) was added. The
precipitate formed was filtered off and air-dried to give 0.85 g
(77%) of 4, yellowish crystals: mp 188-190 °C [lit.11 mp 142-
143.5 °C for monohydrate]; 1H NMR (acetone-d6) δ 8.80 (br s,
2H), 9.03 (s, 2H) (the signal of the enolic proton was not
registered probably because it was too broad or outside the
recorded range).
This hypothesis can explain why reaction of 2,4,6-
trinitrobenzonitrile containing the relatively small, linear
cyano group with benzylmercaptan salt shows a lack of
regioselectivity. It fails, though, to explain why N,N-
disubstituted 2,4,6-trinitrobenzamides (17 and 18) react
with S-, O-, and N-nucleophiles to afford para products
instead of ortho products. N,N-Dialkylaminocarbonyl
groups in these compounds should have similar electronic
properties compared to N-(un)substituted 2,4,6-trini-
trobenzamides. Sterically, N,N-dialkylaminocarbonyl
groups are even larger than N-alkyl(aryl)aninocarbonyl
groups in compounds 8-16 and, therefore, should push
o-nitro groups out of the plane of the aromatic ring even
more effectively.
We suggest that the nucleophilic substitution reactions
of 1-R-2,4,6-trinitrobenzenes are predominantly (but not
exclusively) governed by steric and electronic effects of
R affecting the energies of para and ortho substitution
transition states. Large 1-substituents could probably
facilitate ortho attack (by providing noncoplanarity of the
o-nitro groups) as well as hinder it (by sterically blocking
the ortho reaction sites). There should be some optimal
size of the 1-substituent for selective ortho substitution.
Too small substituentsssuch as the cyano groupslead
to nonselective reaction, while too largessuch as dialky-
lamido groupsscould result in selective para substitution
(see also ref 20).
4-P icr ylisoxa zole (5). To a solution of picrylmalonaldehyde
(4) (0.20 g, 0.71 mmol) in boiling water (7 mL) was added
hydroxylamine hydrochloride (0.50 g) and the reaction mixture
There are probably additional factors that could be
responsible for high ortho selectivity in reactions of
N-monosubstituted 2,4,6-trinitrobenzamides (7-16) com-
pared to N,N-disubstituted 2,4,6-trinitrobenzamides (17
and 18): e.g., the presence of NH hydrogen atoms. These
hydrogen atoms could probably be involved in a transition
state (e.g., by coordination with a nucleophile) to facilitate
selective ortho substitution even in the cases of bulky
amido groups (such as t-BuNHCO).
(19) A reviewer suggested two alternative mechanisms for the
substitution reaction: one involving single electron transfer (SET), and
another beginning with initial ipso attack at the carbon bearing the R
group. The SET mechanism is always a possibility for the reaction
involving polynitro compounds and strong reducing agents such as
thiolates. Unfortunately, the current set of the polyniroaromatic
compounds would not allow us to explore this possible mechanism since
we never observe any significant amounts of disulfides in the reaction
mixtures. In addition, other nucleophiles less prone for oxidation (e.g.,
azide anion or methoxide anion), show essentially the same substitu-
tion pattern. It would be of interest to investigate this possible
mechanism in future studies providing that the appropriate set of
polynitrocompounds will be found. The ipso-attack mechanism pro-
vides a very elegant explanation of the predominant ortho-substitution
pattern found in many 1-R-2,4,6-trinitrobenzenes. According to the
proposed mechanism, ipso-attack at 1 position is preferred since in
the Meisenheimer complex both the sulfur and R-group are out of the
ring plane. This structural feature allows o-nitro groups to assume
in-plane positions and to stabilize the Meisenheimer complex. In this
complex ortho-substitution is more likely (the 1,2-migration compared
to a 1,4 migration). It is also suggested that in the case of large
R-groups a slower, “classical” nucleophilic attack could give the para-
product, or ortho/ para mixture. We would like to add that this
assumption alone cannot fully explain the difference between N,N-
disubstituted trinitrobenzamides (exclusive para-substitution) and
N-substituted trinitrobenzamides (preferred ortho-substitution, even
in the case of bulky amido groups such as t-BuNHCO). Hydrogen bond
formation is possibly playing a role in the rearrangement of the
Meisenheimer complex that forms as a result of ipso-attack at 1
position. This hydrogen bond formation should decelerate 1,4-migration
of a nucleophile compared to 1,2-migration because 1,2-migration does
not require H‚‚‚Nu bond cleavage in the transition state and 1,4-
migration does. Further investigations may be required to support the
ipso-attack mechanism.
We cannot currently offer a reasonable explanation of
the lack of regioselectivity in the reactions of 1,2-disub-
stituted 4,6-dinitroaromatics with benzylmercaptan. This
phenomenon requires further investigation.
Con clu sion s
In summary, reactions of 1-substituted-2,4,6-trini-
troaromatics with alkyl(aryl)thiols and some other nu-
cleophiles have been systematically investigated. Influ-
ence of the nature of substituents in the benzene ring on
the reactivity of polynitroaromatics and regioselectivity
of the nucleophilic substitution reactions have been
elucidated. A series of new sulfur-containing dinitroaro-
matics (intermediates for synthesis of fused heterocycles)
has been synthesized. These results can be used for
development of methods of synthetic utilization of polyni-
troaromatic compounds.
(20) Another reviewer provided a valuable suggestion that there are
two steric effects for this ASN reaction: (a) an accelerating effect caused
by substituents at position 1 tipping o-nitro groups and (b) a decelerat-
ing effect by very bulky substituents at position 1 causing too much
steric hindrance for the sp2 f sp3 transition necessary for the ASN
transformation.
(17) Norris, J . F.; Young, H. H. J . Am. Chem. Soc. 1935, 57(8), 1420.
(18) Montague, M. P. J . Rec. Trav. Chim. Pays-Bas 1902, 21, 376.

Synthetic Utilization of Polynitroaromatic Compounds
J . Org. Chem., Vol. 65, No. 25, 2000 8435
was refluxed for 5 min. The precipitate formed was filtered
off, air-dried to afford 0.16 g (80%) of 5: mp 195-197 °C [lit.11
mp 197-198 °C]; 1H NMR (acetone-d6) δ 8.74 (s, 1H), 9.07 (s,
1H), 9.18 (s, 2H).
N-Ben zyl-2,4,6-tr in itr oben za m id e (10): 2.3 g (60%); mp
253-254 °C; Rf 0.16 (CCl4-acetone 4:1); 1H NMR (DMSO-d6):
4.58 (d, J ) 7.0 Hz, 2H), 7.23-7.45 (m, 5H), 8.56 (br s, 1H),
9.15 (s, 2H). Anal. Calcd for C14H10N4O7: C, 48.55; H, 2.91; N,
16.19. Found: C, 48.83; H, 2.75; N, 16.31.
2,4,6-Tr in itr op h en yla cetic Acid . To a vigorously stirred
solution of â-(2,4,6-trinitrophenyl)ethanol13 (2.57 g, 10.0 mmol)
in concentrated H2SO4 (d ) 1.84, 20 mL) was added CrO3 (3
g, 30.0 mmol) in small portions. During the addition, the
temperature of the reaction mixture was maintained at 30 °C
by external cooling. Then the mixture was heated at 50 °C for
1 h and at 80 °C for 2 h, cooled to room temperature, and
poured into ice water. The precipitate was filtered off, and
recrystallized successively from a mixture of water, EtOH, and
AcOH (1:1:1) and finally from a mixture of hexane and ethyl
acetate to afford 2.1 g (77%) of 2,4,6-trinitrophenyl acetic
acid: mp 163-164 °C [lit.13 mp 163-165 °C].
2,4,6-Tr in itr oben zoyl Ch lor id e (6). To a stirred solution
of SOCl2 (250 mL, 414 g, 3.5 mole) in dry dichloroethane (200
mL) was added successively 2,4,6-trinitrobenzoic acid (TNBA)
(257 g, 1.0 mole) and DMF (10 mL) at 20 °C (technical grade
TNBA, prepared by oxidation of TNT with HNO3, was used
in the reaction without additional purification). The reaction
mixture was gradually warmed to 70 °C for 2 h and stirred
for 1 h at that temperature. It was then cooled to 0 °C and
maintained at 0 °C for 1 h. The precipitate was filtered off,
washed with 1,2-dichloroethane (50 mL), and air-dried to
afford 192 g (70%) of 6: mp 158 °C [lit.17 mp 158-158.5 °C].
The same procedure carried out on 20 g scale using purified
TNBA afforded the compound (6) in 90% yield.
N-P h en yl-2,4,6-tr in itr oben za m id e (11): 2.9 g (79%); mp
219-221 °C; Rf 0.17 (CCl4-acetone 4:1); 1H NMR (DMSO-d6)
δ 7.20 (t, J ) 7.5 Hz, 1H), 7.42 (t, J ) 7.5 Hz, 2H), 7.56 (d, J
) 7.5 Hz, 2H), 9.20 (s, 2H), 11.05 (br s, 1H). Anal. Calcd for
C
13H8N4O7: C, 46.98; H, 2.43; N, 16.87. Found: C, 47.29; H,
2.37; N, 17.01;
N-(4′-Br om op h en yl)-2,4,6-tr in itr oben za m id e (12): yel-
low-brownish crystals; 3.1 g (69%); mp 241-243 °C; Rf 0.59
(benzene-acetone 4:1); 1H NMR (DMSO-d6) δ 7.50 (s, 4H), 9.15
(s, 2H), 11.00 (br s, 1H). Anal. Calcd for C13H7BrN4O7: C,
37.98; H, 1.72; N, 13.63; Br, 19.44. Found: C, 38.12; H, 1.85;
N, 13.39; Br, 19.27;
N-(2′-Eth oxyca r bon ylp h en yl)-2,4,6-tr in itr oben za m id e
(13): bright-yellow crystals; 2.7 g (62%); mp 157-158 °C; Rf
0.55 (benzene); 1H NMR (DMSO-d6) δ 1.35 (t, J ) 7.0 Hz, 3H),
4.30 q (J ) 7.0 Hz, 2H), 7.32 (t, J ) 8.0 Hz, 1H), 7.69 (t, J )
8.0 Hz, 1H), 8.00 (d, J ) 8.0 Hz, 1H), 8.23 (d, J ) 8.0 Hz, 1H),
9.20 (s, 2H), 11.05 (s, 1H). Anal. Calcd for C16H12N4O9: C,
47.53; H, 2.99; N, 13.86. Found: C, 47.29; H, 3.11; N, 13.68;
N-(3′-ca r boxyp h en yl)-2,4,6-tr in itr oben za m id e (14): col-
orless crystals; 3.0 g (73%); mp >310 °C; Rf 0.23 (benzene-
1
acetone 4:1); H NMR (DMSO-d6) δ 7.50 (t, J ) 8.0 Hz, 1H),
7.75 (d, J ) 8.0 Hz, 1H), 7.81 (d, J ) 8.0 Hz, 1H), 8.15 (s, 1H),
9.16 (s, 2H), 11.12 (s, 1H), 12.80 (br s, 1H). Anal. Calcd for
2,4,6-Tr in itr oben za m id es (7, 8) (Meth od A). A 30%
ammonia (or 30% water solution of methylamine) (5 mL) was
diluted with water (100 mL) and cooled to 6 °C. To the solution
was added dropwise a solution of 2,4,6-trinitrobenzoic acid
chloride (6) (5,0 g, 18.2 mmol) in benzene (100 mL) with
intensive stirring maintaining the temperature at 6 °C by
external cooling. The reaction mixture was stirred at 5-6 °C
for 2 h and acidified to pH ∼2 by addition of 10% HCl. The
precipitate of the compound 7 or 8 was filtered off, washed
successively with water (2 × 50 mL), benzene (2 × 50 mL),
air-dried, and crystallized from i-PrOH-acetone mixture to
afford the following compounds.
C13H8N4O7: C, 44.69; H, 2.14; N, 14.89. Found: C, 44.95; H,
2.27; N, 14.72;
N,N-Dieth yl-2,4,6-tr in itr oben za m id e (17): 2.85 g (84%);
mp 134-135 °C; Rf 0.37 (CCl4-acetone 4:1); 1H NMR (DMSO-
d6) δ 1.07 (t, J ) 7.5 Hz, 3H), 1.24 (t, J ) 7.5 Hz, 3H), 3.19 q
(J ) 7.5 Hz, 2H), 3.52 q (J ) 7.5 Hz, 2H), 9.16 (s, 2H). Anal.
Calcd for C11H12N4O7: C, 42.31; H, 3.87; N, 17.94. Found: C,
42.55; H, 3.47; N, 18.12;
2,4,6-Tr in itr oben zoic a cid m or p h olid e (18): pale-yellow
crystals; 2.2 g (61%); mp 195-196 °C; Rf 0.57 (benzene-
acetone 4:1); 1H NMR (DMSO-d6): δ 3.28 (t, J ) 4.5 Hz, 2H),
3.57 (t, J ) 4.5 Hz, 2H), 3.70 (t, J ) 4.5 Hz, 2H), 3.75 (t, J )
4.5 Hz, 2H), 9.16 (s, 2H). Anal. Calcd for C11H10N4O8: C, 40.50;
H, 3.09; N, 17.17. Found: C, 40.65; H, 3.17; N, 17.01.
N -(4′-Tr iflu or om e t h oxyp h e n yl)-2,4,6-t r in it r ob e n z-
a m id e (15). To a stirred solution of 2,4,6-trinitrobenzoyl
chloride (0.98 g, 3.6 mmol) in absolute benzene (10 mL) were
added successively 4-(trifluoromethoxy)aniline (0.63 g, 3.6
mmol) and then during 3 h a solution of triethylamine (0.49
mL, 0.36 g, 3.5 mmol) in absolute benzene (1 mL). The reaction
mixture was stirred at 15 °C for an additional 2 h. The
precipitate was filtered off, washed with benzene (3 × 2 mL)
and water (3 × 5 mL), air-dried, and crystallized from a
i-PrOH-heptane mixture to afford 0.98 g (66%) of 15: yellow
2,4,6-Tr in itr oben za m id e (7): 2.51 g (54%); mp 270-273
°C (lit.18 mp 264 °C dec).
N-Meth yl-2,4,6-tr in itr oben za m id e (8): 3.72 g (76%); mp
296-297 °C (lit.18 mp 285 °C dec); Rf 0.09 (CCl4-acetone 4:1);
1H NMR (DMSO-d6) δ 2.85 (d, J ) 5.0 Hz, 3H), 8.80 (br s,
1H), 9.07 (s, 2H).
2,4,6-Tr in itr oben za m id e (7) (Meth od B). 2,4,6-Trini-
trobenzoic acid (128 g, 0.5 mole) was dissolved in oleum
containing 30% of SO3. To the vigorously stirred solution was
added urea (30.0 g, 0.51 mole) in small portions at 50-55 °C
during 2 h (Ca u tion ! The reaction has an induction period).
An intensive foaming took place during the addition. After
finishing the addition, the reaction mixture was heated at 95-
100 °C for 3 h with stirring, cooled to room temperature, and
poured onto stirred crushed ice (∼2 Kg). The precipitate was
filtered off, washed thoroughly with ice water, dried in the air.
The product was suspended in acetone:benzene:hexane (1:1:
1) mixture, filtered off, dried in the air to afford 110 g (90%)
of 7; mp 264 °C. According to TLC and 1H NMR the product
was identical to the compound (7) prepared by method A.
2,4,6-Tr in itr oben za m id es (9-14, 17, a n d 18). To a stirred
solution of 2,4,6-trinitrobenzoyl chloride (6) (3.0 g, 10.9 mmol)
in absolute benzene (35 mL) was added alkylamine or aryl-
amine (21.8 mmol). The reaction mixture was stirred at 15-
40 °C for 2-5 h (the reaction conditions for each compound
are given in Table 1). The precipitate was filtered off, washed
with benzene (3 × 5 mL) and water (3 × 5 mL), air-dried, and
crystallized from a i-PrOH-acetone mixture to afford the
following compounds.
1
crystals; mp 241-244 °C; Rf 0.53 (benzene-acetone 4:1); H
NMR (DMSO-d6) δ 7.31 (d, J ) 8.5 Hz, 2H), 7.70 (d, J ) 8.5
Hz, 2H), 9.19 (s, 2H), 11.08 (br s, 1H). Anal. Calcd for
C
14H7F3N4O8: C, 40.40; H, 1.70; N, 13.46; F. 13.69. Found: C,
40.66; H, 1.85; N, 13.29; F. 13.44.
N-(4′-Ch lor od iflu or om eth oxyph en yl)-2,4,6-tr in itr oben -
za m id e (16). To a stirred solution of 2,4,6-trinitrobenzoyl
chloride (1.03 g, 3.74 mmol) in absolute benzene (10 mL) were
added successively 4-(clorodifluoromethoxy)aniline (0.73 g, 4.12
mmol) and then during 3 h a solution of triethylamine (0.51
mL, 0.37 g, 3.66 mmol) in absolute benzene (1 mL). The
reaction mixture was stirred at 15 °C for additional 2 h. The
precipitate was filtered off, washed with benzene (3 × 2 mL)
and water (3 × 5 mL), air-dried, and crystallized from an
i-PrOH-heptane mixture to afford 0.77 g (49%) of 16: yellow
1
crystals; mp 229-233 °C; Rf 0.50 (benzene-acetone 4:1); H
NMR (DMSO-d6) δ 7.31 (d, J ) 8.5 Hz, 2H), 7.68 (d, J ) 8.5
Hz, 2H), 9.17 (s, 2H), 11.13 (br s, 1H). Anal. Calcd for C14H7-
ClF2N4O8: C, 38.86; H, 1.63; N, 12.95; Cl, 8.19; F. 8.78.
Found: C, 39.16; H, 1.65; N, 12.79; Cl, 8.11; F. 8.64.
N-ter t-b u t yl-2,4,6-t r in it r ob en za m id e (9): 1.9 g (56%);
mp 240-242 °C; Rf 0.21 (CCl4-acetone 4:1); 1H NMR (DMSO-
d6) δ 1.32 (s, 9H), 8.69 (s, 1H), 9.08 (s, 2H). Anal. Calcd for
C
11H12N4O7: C, 42.31; H, 3.87; N, 17.94. Found: C, 42.43; H,
2,4,6-Tr in itr op h en yla cetic Acid An ilid e (19). A mixture
of 2,4,6-trinitrophenylacetic acid (0.50 g, 1.8 mmol), thionyl
3.75; N, 17.99.

8436 J . Org. Chem., Vol. 65, No. 25, 2000
Zlotin et al.
chloride (0.40 mL, 0.66 g, 5.6 mmol), and absolute benzene (3
mL) was refluxed for 4 h. A clear solution formed at the end
of this period. The solvent and excess of SOCl2 were removed
under reduced pressure. An additional portion of absolute
benzene (2 mL) was added to the remaining viscous oil and
evaporated in vacuo. The procedure was repeated once more
to remove traces of SOCl2 completely. Finally, to the residue
was added absolute benzene (4 mL) and then was added
aniline (0.41 g, 4.4 mmol) with stirring. The reaction mixture
was stirred at 15 °C for 2 h and then kept for an additional
12 h at the same temperature. The precipitate was filtered
off, washed with benzene (1 mL) and water (2 × 2 mL), air-
dried, and crystallized from an i-PrOH-acetone mixture to
afford 0.40 g (58% based on 2,4,6-trinitrophenyl acetic acid)
of 19: mp 229-231 °C; 1H NMR (DMSO-d6) δ 4.34 (s, 2H),
7.03 (t, J ) 7.5 Hz, 1H), 7.28 (t, J ) 7.5 Hz, 2H), 7.51 (d, J )
7.5 Hz, 2H), 9.05 (s, 2H), 10.20 (br s, 1H). Anal. Calcd for
2H), 7.20-7.35 (m, 3H), 7.42 (d, J ) 7.0 Hz, 2H), 8.32 s(1H),
8.40 (s, 1H); 1H NMR of 23a (DMSO-d6) δ 2.40 (s, 3H), 4.39 (s,
2H), 7.20-7.35 (m, 3H), 7.42 (d, J ) 7.0 Hz, 2H), 8.05 (s, 2H).
Anal. Calcd for C14H12N2O4S: C, 55.25; H, 3.98; N, 9.21; S,
10.52. Found: C, 55.44; H, 3.89; N, 9.08; S, 10.39.
N-[2′,4′-Din itr o-6′-(p h en ylth io)ben zylid en e]-4-d im eth -
yla m in o a n ilin e (24). To a solution of N-(2′,4′,6′-trinitroben-
zylidene)-4-dimethylaminoaniline (1)9,10 (0.60 g, 1.7 mmol) in
96% EtOH (20 mL) were added successively thiophenol (0.19
g, 1.7 mmol) and powdered KOH (0.093 g, 1.7 mmol). The
reaction mixture was stirred for 10 h at 15 °C and then diluted
with water (30 mL). The precipitate was filtered off, washed
with water, and crystallized to afford 0.15 g (21%) of 24: mp
167-168 °C; 1H NMR (DMSO-d6): δ 3.08 (s, 6H), 6.74 (d, J )
8.5 Hz, 2H), 7.70 (d, J ) 8.5 Hz, 2H), 7.48-7.60 (m, 5H), 8.00
(d, J ) 2.0 Hz, 1H), 8.52 (d, J ) 2.0 Hz, 1H), 8.60 (s, 1H).
Anal. Calcd for C21H18N4O4S: C, 59.71; H, 4.29; N, 13.26; S,
7.59. Found: C, 59.94; H, 4.22; N, 13.07; S, 7.43.
C
14H10N4O7: C, 48.56; H, 2.91; N, 16.18. Found: C, 48.78; H,
3.07; N, 16.02.
4-[2,4-Din itr o-6-(p -tolylth io)p h en yl]isoxa zole (25). A
mixture of 4-picrylisoxazole (5) (0.30 g, 1.1 mmol), p-tolylm-
ercaptan (0.14 g, 1.1 mmol), K2CO3 (0.15 g, 1.1 mmol) and
absolute DMSO (2 mL) was stirred for 2 h at 15 °C and then
poured into cold water (15 mL). After 2 h, the precipitate was
filtered off, washed with water, and crystallized from 96%
EtOH to afford 0.20 g (52%) of 25: brownish crystals; mp 168-
2,4-Din itr o-6-(4′-tolylth io)tolu en e (20). To a solution of
p-tolylmercaptan (0.62 g, 5.00 mmol) in absolute DMSO (5 mL)
were added successively KOH (0.12 g, 5.02 mmol) and TNT
(1.13 g, 4.98 mmol). The resulting dark suspension was stirred
for 10 h at 15 °C. The precipitate was filtered off, washed with
water, and crystallized from 96% EtOH to afford 1.06 g (70%)
of 20: yellowish crystals; mp 97-98 °C; 1H NMR (acetone-d6)
δ 2.42 (s, 3H), 2.61 (s, 3H), 7.41 (d, J ) 7.0 Hz, 2H), 7.52 (d, J
) 7.0 Hz, 2H), 7.87 (s, 1H), 8.42 (s, 1H). Anal. Calcd for
1
169 °C; H NMR (acetone-d6) δ 2.40 (s, 3H), 7.41 (d, J ) 8.0
Hz, 2H), 7.49 (d, J ) 8.0 Hz, 2H), 7.82 (d, J ) 2 Hz, 1H), 8.52
(d, J ) 2 Hz, 1H), 8.77 (s, 1H), 9.10 (s, 1H). Anal. Calcd for
C16H11N3O5S: C, 53.78; H, 3.10; N, 11.76; S, 8.97. Found: C,
C
14H12N2O4S: C, 55.25; H, 3.98; N, 9.21; S, 10.52. Found: C,
55.53; H, 4.02; N, 9.39; S, 10.30.
54.00; H, 3.23; N, 11.59; S, 8.80.
The same reaction with LiOH instead of KOH gave the
compound 20 in 42% yield.
(2-Ben zylt h io-4,6-d in it r op h en yl)a cet ic Acid An ilid e
(26). To a stirred solution of 2,4,6-trinitrophenylacetic acid
anilide (19) (0.50 g, 1.44 mmol) in absolute DMF (3 mL) were
added successively benzylmercaptan (0.20 mL, 0.21 g, 1.70
mmol) and Na2CO3 (0.20 g, 1.80 mmol). The reaction mixture
was stirred at 15 °C for 4 h and poured into a saturated NaCl
water solution (∼20 mL). A dark oil gradually became solid
upon standing for several hours. The solid was filtered off,
washed with water (2 × 3 mL), dried in the air, and crystal-
lized from a benzene-heptane mixture to afford 0.27 g (46%)
of 26: mp 167-172 °C; 1H NMR (DMSO-d6) δ 4.28 (s, 2H),
4.43 (s, 2H), 7.02 (m, 2H), 7.20-7.45 (m, 5H, 5CH), 7.53 (m,
3H), 8.40 (d, J ) 2.0 Hz, 1H), 8.55 (d, J ) 2.0 Hz, 1H), 10.20
(br s, 1H). Anal. Calcd for C21H17N3O5S: C, 59.57; H, 4.05; N,
9.92; S, 7.57. Found: C, 59.38; H, 3.93; N, 10.04; S, 7.69.
2,4-Din itr o-6-(p h en ylth io)ben za ld eh yd e (27). A mixture
of N-[2′,4′-dinitro-6′-(phenylthio)benzylidene]-4-(dimethylami-
no)aniline (24) (4.5 g, 11 mmol) and concentrated HCl (d )
1.17) was refluxed until all the starting compound was con-
sumed. The reaction mixture was cooled to room temperature,
and the precipitate was filtered off, washed with water, and
crystallized from benzene to afford 1.5 g (46%) of 27: mp 109-
110 °C; 1H NMR (DMSO-d6) δ 7.55-7.65 (m, 5H), 7.90 (s, 1H),
8.58 (s, 1H), 10.31 (s, 1H). Anal. Calcd for C13H8N2O5S: C,
51.32; H, 2.65; N, 9.21; S, 10.54. Found: C, 51.49; H, 2.77; N,
9.12; S, 10.31.
2-Alkylthio-4,6-dinitr obenzam ides (28a-37a)an d 4-Alkyl-
th io-2,6-d in itr oben za m id es (28b-40b). To a solution of
2,4,6-trinitrobenzamide (7-12, 15-18) (15 mmol) in DMF (20
mL) were added successively with stirring thiol (15 mmol) and
K2CO3 (2.2 g, 16 mmol). In the case of 30a and 30b the
commercially available sodium thiomethylate (1.05 g, 15 mmol)
was used instead of a mixture of the thiol and K2CO3. The
reaction mixture was stirred for 4 h at 15 °C, poured to water
(50 mL), and neutralized to pH∼6-7 by addition of 10% HCl.
After 12 h, the precipitate was filtered off, washed with water
(2 × 5 mL), air-dried, and crystallized from i-PrOH-acetone
mixture to afford the following compounds.
2-(5′-Br om o-2′-flu or op h en ylsu lfa n yl)-4,6-d in it r ot ol-
u en e (21). To a solution of 3-bromo-6-fluorophenylmercaptan
(1.0 g, 5.0 mmol) in absolute DMF (5 mL) were added
successively powdered KOH (0.35 g, 6.3 mmol) and TNT (1.1
g, 5.0 mmol). The reaction mixture was stirred for 10 h at 15
°C and then diluted with slightly acidified water (15 mL). The
precipitate was filtered off, washed with water and crystallized
from 96% EtOH-Et2O (1:1) mixture to afford 1.10 g (58%) of
21: yellow powder; mp 92-93 °C; 1H NMR (acetone-d6) δ 2.68
(s, 3H), 7.40 (t, J ) 9 Hz, 1H), 7.75-7.82 (m, 2H), 8.12 (s, 1H),
8.60 (s, 1H). Anal. Calcd for C13H8BrFN2O4S: C, 40.33; H, 2.08;
N, 7.24; S, 8.28. Found: C, 40.62; H, 1.92; N, 7.37; S, 8.09.
The same reaction being carried out in DMSO instead of
DMF gave the compound 21 in only 20% yield.
2,4-Din itr o-6-[(m eth oxyca r bon yl)m eth ylth io]tolu en e
(22). To a solution of methyl mercaptoacetate (0.55 g, 5.2
mmol) in absolute DMF (3 mL) were added successively
K2CO3 (0.70 g, 5.1 mmol) and TNT (1.13 g, 4.98 mmol). The
resulting deep violet solution was stirred for 4 h at 15 °C and
then for 4 h at 50 °C. The reaction mixture was cooled to room
temperature and poured into water (∼20 mL). A dark oil
precipitated that solidified upon standing. The liquid was
decanted, the solid was air-dried and dissolved in CHCl3, and
the solution was filtered through a short (2 cm) silica gel
column. The yellowish CHCl3 solution was evaporated to
dryness in vacuo, and the residue (yellow oil) was crystallized
by treating with ether to afford 0.63 g (44%) of 22: colorless
crystals; mp 72-73 °C (ether); 1H NMR (CDCl3) δ 2.61 (s, 3H),
3.70 (s, 3H, OCH3), 3.75 (s, 2H), 8.40 (d, J ) 2 Hz, 1H), 8.44
(d, J ) 2 Hz, 1H). Anal. Calcd for C10H10N2O6S: C, 41.96; H,
3.52; N, 9.79; S, 11.20. Found: C, 42.13; H, 3.53; N, 9.57; S,
11.02.
2-Ben zylth io-4,6-d in itr otolu en e (23). To a solution of
benzyl mercaptan (0.62 g, 5.0 mmol) in absolute DMSO (2.5
mL) were added successively K2CO3 (0.69 g, 5.0 mmol) and
TNT (1.1 g, 5.0 mmol). The reaction mixture was stirred for 1
h at 40 °C, cooled to room temperature, and poured into cold
water (∼10 mL). The precipitate was filtered off and dissolved
in ethyl acetate, and the solution was passed through a short
silica gel column. Evaporation of the solvent afforded 0.61 g
(40%) of 2-benzylthio-4,6-dinitrotoluene (23), containing (1H
NMR) about 7% of 4-benzylthio-2,6-dinitrotoluene (23a ): mp
115-116 °C; 1H NMR of 23 (DMSO-d6) δ 2.55 (s, 3H), 4.45 (s,
Mixtu r e of 2-(ben zylth io)-4,6-d in itr oben za m id e (28a )
a n d 4-(ben zylth io)-2,6-d in itr oben za m id e (28b): pale-yel-
low crystals; 4.14 g (83%); mp 192-194 °C; Rf 0.60 (CHCl3-
acetone 5:1); 1H NMR of 28a (DMSO-d6) δ 4.48 (s, 2H), 7.23-
7.48 (m, 5H), 7.90 (br s, 1H), 8.10 (br s, 1H), 8.41 (s, 1H), 8.56
(s, 1H). Anal. Calcd for C14H11N3O5S: C, 50.45; H, 3.33; N,
12.61; S, 9.62. Found: C, 50.69; H, 3.50; N, 12.79; S, 9.40.

Synthetic Utilization of Polynitroaromatic Compounds
J . Org. Chem., Vol. 65, No. 25, 2000 8437
Mixtu r e of 2-(m eth oxyca r bon ylm eth ylth io)-4,6-d in i-
tr oben zam ide (29a) an d 4-(m eth oxycar bon ylm eth ylth io)-
2,6-d in itr oben za m id e (29b): pale-yellow crystals; 3.59 g
(d, J ) 8.0 Hz, 2H), 8.40 (s, 2H in 36b), 8.54 (s, 1H), 8.65 (s,
1H), 10.99 (br s, 1H). Anal. Calcd for C21H14N3O6F3S: C, 51.12;
H, 2.86; N, 8.52; F, 11.55; S, 6.50. Found: C, 51.34; H, 2.93;
N, 8.39; F. 11.36; S, 6.29.
1
(76%); mp 175-178 °C; Rf 0.08 (CCl4-acetone 4:1); H NMR
of 29a (DMSO-d6) δ 3.72 (s, 3H), 4.12 (s, 2H), 7.92 (br s, 1H),
Mixtu r e of N-(4′-ch lor od iflu or om eth oxyp h en yl)-2-ben -
zylt h io-4,6-d in it r oben za m id e (37a ) a n d N-(4′-ch lor od i-
flu or om eth oxyph en yl)-4-ben zylth io-2,6-din itr oben zam ide
(37b): 4.6 g (59%); mp 160-165 °C; Rf 0.60 (benzene-acetone
4:1); 1H NMR spectra of the mixture (DMSO-d6) δ 4.48 (s, 2H),
7.30 (m, 5H), 7.37 (d, J ) 8.0 Hz, 2H), 7.73 (d, J ) 8.0 Hz,
2H), 8.33 (s, 2H in 37b), 8.50 (s, 1H), 8.65 (s, 1H), 10.89 (br s,
1H). Anal. Calcd for C21H14N3ClF2O6S: C, 49.47; H, 2.77; N,
8.24; S, 6.29. Found: C, 49.30; H, 2.71; N, 8.35; S, 6.53.
4-Ben zylth io-2,6-d in itr o-N,N-d ieth ylben za m id e (38b):
pale yellow crystals; 4.96 g (85%); mp 85-87 °C; Rf 0.46 (CCl4-
8.09 (br s, 1H), 8.59 (s, (1H), 8.60 (s, 1H). Anal. Calcd for
C
10H9N3O7S: C, 38.10; H, 2.88; N, 13.33; S, 10.17. Found: C,
38.29; H, 2.60; N, 13.19; S, 10.15.
Mixtu r e of 2-(m eth ylth io)-4,6-d in itr oben za m id e (30a )
a n d 4-(m eth ylth io)-2,6-d in itr oben za m id e (30b): pale-yel-
low crystals; 2.89 g (75%); mp 213-215 °C; Rf 0.10 (CCl4-
1
acetone 4:1), H NMR of 30a (DMSO-d6) δ 2.67 (s, 3H), 7.91
(br s, 1H), 8.08 (br s, 1H), 8.32 (s, 1H), 8.51 (s, 1H). Anal. Calcd
for C8H7N3O5S: C, 37.36; H, 2.74; N, 16.34; S, 12.46. Found:
C, 37.39; H, 2.60; N, 16.29; S, 12.40.
1
Mixtu r e of 2-ben zylth io-4,6-d in itr o-N-m eth ylben z-
a m id e (31a ) a n d 4-ben zylth io-2,6-d in itr o-N-m eth yl ben z-
a m id e (31b): pale-yellow crystals; 3.23 g (62%); mp 152-156
°C; Rf 0.19 (CCl4-acetone 4:1); signals of the compound 31a
in 1H NMR of the mixture (DMSO-d6) δ 2.79 (d, J ) 5.0 Hz,
3H), 4.48 (s, 2H), 7.25-7.45 (m, 5H), 8.42 (d, J ) 1.5 Hz, 1H),
8.57 (d, J ) 1.5 Hz, 1H), 8.62 (br s, 1H); signals of the
compound 31b in 1H NMR of the mixture (DMSO-d6) δ 2.71
(d, J ) 5.0 Hz, 3H), 4.53 (s, 2H), 7.25-7.45 (m, 5H), 8.29 (s,
2H), 8.62 (br s, 1H). Anal. Calcd for C15H13N3O5S: C, 51.87;
H, 3.77; N, 12.10; S, 9.23. Found: C, 51.78; H, 3.89; N, 11.95;
S, 9.34.
acetone 4:1); H NMR (DMSO-d6) δ 0.96 (t, J ) 7.5 Hz, 3H),
1.24 (t, J ) 7.5 Hz, 3H), 3.12 q (J ) 7.5 Hz, 2H), 3.43 q (J )
7.5 Hz, 2H), 4.53 (s, 2H), 7.25-7.45 (m, 5H), 8.39 (s, 2H); 13C
NMR (DMSO-d6) δ 11.36, 12.83, 35.70, 42.37, 38.29, 120.32,
127.25, 127.54, 128.58, 128.92, 135.63, 141.97, 146.24, 160.99.
Anal. Calcd for C18H19N3O5S: C, 55.52; H, 4.92; N, 10.79; S,
8.23. Found: C, 55.49; H, 4.99; N, 10.85; S, 8.32.
4-Ben zylth io-2,6-din itr oben zoic acid m or ph olide (39b):
pale yellow crystals; 5.32 g (88%); mp 152-156 °C; Rf 0.19
(CCl4-acetone 4:1); 1H NMR (DMSO-d6) δ 3.21 (t, J ) 4.5 Hz,
2H), 3.53 (t, J ) 4.5 Hz, 2H), 3.62 (t, J ) 4.5 Hz, 2H), 3.71 (t,
J ) 4.5 Hz, 2H), 4.47 (s, 2H), 7.25-7.45 (m, 5H), 8.32 (s, 2H);
13C NMR (DMSO-d6): δ 35.97, 42.12, 46.44, 65.61, 65.73,
122.62, 127.36, 127.87, 128.91, 129.19, 135.90, 142.84, 146.67,
160.95. Anal. Calcd for C18H17N3O6S: C, 53.59; H, 4.25; N,
10.42; S, 7.95. Found: C, 53.68; H, 4.20; N, 10.49; S, 7.83.
4-(Met h oxyca r b on ylm et h ylt h io)- 2,6-d in it r ob en zoic
a cid m or p h olid e (40b): pale yellow crystals; 4.39 g (76%);
mp 152-156 °C; Rf 0.19 (CCl4-acetone 4:1); 1H NMR (DMSO-
d6) δ 3.24 (t, J ) 4.5 Hz, 2H), 3.52 (t, J ) 4.5 Hz, 2H), 3.61 (t,
J ) 4.5 Hz, 2H), 3.66 (t, J ) 4.5 Hz, 2H), 3.71 (s, 3H), 4.29 (s,
2H), 8.47 (s, 2H); 13C NMR (DMSO-d6) δ 33.41, 41.82, 46.13,
65.30, 65.45, 52.54, 122.67, 127.13, 141.56, 146.36, 160.63,
168.93. Anal. Calcd for C14H15N3O8S: C, 43.64; H, 3.92; N,
10.90; S, 8.32. Found: C, 43.58; H, 3.88; N, 10.97; S, 8.39.
2,4-Din itr o-6-m eth oxy-N-p h en ylben za m id e (41a ). To a
solution of N-phenyl-2,4,6-trinitrobenzamide (11) (0.10 g, 0.30
mmol) in absolute DMF (1 mL) were added successively with
stirring CH3OH (0.04 mL, 0.03 g, 0.99 mmol) and K2CO3 (0.05
g, 0.36 mmol). The reaction mixture was stirred at 40 °C for
24 h, poured into water (10 mL). The precipitate was filtered
off, washed with water (2 × 1 mL), dried in the air, and
crystallized from a mixture of acetone and i-PrOH to yield 0.08
g (83%) of 41a : mp 231-234 °C; Rf 0.12 (CCl4-acetone 4:1);
1H NMR (DMSO-d6) δ 4.07 (s, 3H), 7.13 (t, J ) 7.5 Hz, 1H),
7.38 (t, J ) 7.5 Hz, 2H), 7.62 (d, J ) 7.5 Hz, 2H), 8.28 (s, 1H),
8.50 (s, 1H), 10.60 (br s, 1H). Anal. Calcd for C14H11N3O6: C,
53.00; H, 3.49; N, 13.24. Found: C, 53.17; H, 3.56; N, 13.03.
2,4-Din itr o-6-p h en oxy-N-p h en ylben za m id e (42a ). To a
solution of N-phenyl-2,4,6-trinitrobenzamide (11) (0.10 g, 0.30
mmol) in absolute DMF (1 mL) were added successively with
stirring PhOH (0.03 g, 0.32 mmol) and K2CO3 (0.05 g, 0.36
mmol). The reaction mixture was stirred at 40 °C for 24 h,
poured into water (10 mL). The precipitate was filtered off,
washed with water (2 × 1 mL), air-dried, and crystallized from
an acetone-i-PrOH mixture to yield 0.08 g (70%) of 42a : mp
248-254 °C; Rf 0.22 (CCl4-acetone 4:1); 1H NMR (DMSO-d6)
δ 7.10-7.65 (m, 10H), 7.92 (s, 1H), 8.65 (s, 1H), 10.92 (br s,
1H). Anal. Calcd for C19H13N3O6: C, 60.16; H, 3.45; N, 11.08.
Found: C, 60.30; H, 3.53; N, 10.87.
Mixtu r e of 2-ben zylth io-4,6-d in itr o-N-ter t-bu tylben -
za m id e (32a ) a n d 4-ben zylth io-2,6-d in itr o-N-ter t-bu tyl-
ben za m id e (32b): pale-yellow crystals; 4.20 g (72%); mp 154-
157 °C; Rf 0.34 (CCl4-acetone 4:1); signals of the compound
1
32a in H NMR of the mixture (DMSO-d6) δ 1.35 (s, 9H), 4.49
(s, 2H), 7.25-7.45 (m, 5H), 8.41 (d, 1H), 8.46 (d, 1H), 8.56 (br
s, 1H). Anal. Calcd for C18H19N3O5S: C, 55.52; H, 4.92; N,
10.79; S, 8.23. Found: C, 55.58; H, 4.84; N, 10.85; S, 8.31.
Mixtu r e of N-ben zyl-2-ben zylth io-4,6-d in itr oben z-
a m id e (33a ) a n d N-ben zyl-4-ben zylth io-2,6-d in itr oben -
za m id e (33b): pale yellow crystals; 5.39 g (85%); mp 170-
175 °C; Rf 0.26 (CCl4-acetone 4:1); signals of the compound
1
33a in H NMR of the mixture (DMSO-d6) δ 4.48 (s, 2H), 4.63
(d, J ) 7.0 Hz, 2H), 7.23-7.36 (m, 6H), 7.38-7.50 (m, 4H),
8.22 (br s, 1H), 8.48 (s, 1H), 8.63 (s, 1H); signals of the
compound 33b in 1H NMR of the mixture (DMSO-d6) δ 4.57
(d, J ) 7.0 Hz, 2H), 4.59 (s, 2H), 7.23-7.50 (m, 10H), 8.22 (br
s, 1H), 8.28 (s, 2H). Anal. Calcd for C21H17N3O5S: C, 59.57;
H, 4.05; N, 9.92; S, 7.57. Found: C, 59.80; H, 4.19; N, 10.11;
S, 7.35.
Mixtu r e of 2-ben zylth io-4,6-d in itr o-N-p h en ylben z-
a m id e (34a ) a n d 4-ben zylth io-2,6-d in itr o-N-p h en yl ben -
za m id e (34b): pale yellow crystals; 5.52 g (90%); mp 175-
180 °C; Rf 0.22 (CCl4-acetone 4:1); signals of the compound
1
34a in H NMR of the mixture (DMSO-d6) δ 4.54 (s, 2H), 7.10-
7.66 (m, 10H), 8.53 (s, 1H), 8.65 (s, 1H), 10.80 (br s, 1H); signals
of the compound 34b in 1H NMR of the mixture (DMSO-d6) δ
4.58 (s, 2H), 7.10-7.66 (m, 10H), 8.40 (s, 2H), 10.80 (br s, 1H).
Anal. Calcd for C20H15N3O5S: C, 58.67; H, 3.69; N, 10.26; S,
7.83. Found: C, 58.86; H, 3.82; N, 10.08; S, 7.64.
Mixtu r e of 2-ben zylth io-N-(4′-br om op h en yl)-4,6-d in i-
tr oben za m id e (35a ) a n d 4-ben zylth io-N-(4′-br om op h en -
yl)-2,6-d in itr oben za m id e (35b): 6.15 g (84%); mp 187-192
°C; Rf 0.66 (benzene-acetone 4:1); signals of the compound
35a in 1H NMR of the mixture (DMSO-d6) 4.46 (s, 2H), 7.30
(m, 3H), 7.40 (d, J ) 7.5 Hz, 2H), 7.50 (d, J ) 7.5 Hz, 2H),
7.60 (d, J ) 7.5 Hz, 2H), 8.50 (s, 1H), 8.65 (s, 1H), 10.80 (br s,
1H); signals of the compound 35b in 1H NMR of the mixture
(DMSO-d6): 4.51 (s, 2H), 7.30 (m, 3H), 7.40 (d, J ) 7.5 Hz,
2H), 7.50 (d, J ) 7.5 Hz, 2H), 7.60 (d, J ) 7.5 Hz, 2H), 8.32 (s,
2H), 10.80 (br s, 1H). Anal. Calcd for C20H14BrN3O5S: C, 49.19;
H, 2.89; N, 8.61; Br, 16.36; S, 6.57. Found: C, 49.41; H, 3.02;
N, 8.45; Br, 16.12; S, 6.43.
4-Meth oxy-2,6-d in itr oben zoic Acid Mor p h olid e (43b).
To a solution of MeONa [prepared from Na (0.04 g, 1.73 mmol)
and absolute MeOH (10 mL)] was added successively with
stirring 2,4,6-trinitrobenzoic acid morpholide (18) (0.40 g, 1.22
mmol). The reaction mixture was stirred at 18 °C for 24 h,
evaporated to dryness, and then treated with 5% HCl (10 mL).
The precipitate was filtered off, washed with water (2 × 1 mL),
air-dried, and crystallized from an acetone-i-PrOH mixture
to yield 0.32 g (83%) of 43b: mp 185-188 °C; Rf 0.10 (CCl4-
Mixtu r e of 2-ben zylth io-4,6-d in itr o-N-(p -tr iflu or o-
m eth oxyp h en yl)ben za m id e (36a ) a n d 4-ben zylth io-2,6-
d in itr o-N-(p -tr iflu or om eth oxyp h en yl)ben za m id e (36b):
4.80 g (65%); mp 178-180 °C; 1H NMR of the mixture (DMSO-
d6) δ 4.51 (s, 2H), 4.58 (s, 2H in 36b), 7.20-7.45 (m, 7H), 7.72
1
acetone 4:1); H NMR (DMSO-d6) δ 3.21 (t, J ) 4.5 Hz, 2H),

8438 J . Org. Chem., Vol. 65, No. 25, 2000
Zlotin et al.
3.50 (t, J ) 4.5 Hz, 2H), 3.59 (t, J ) 4.5 Hz, 2H), 3.65 (t, J )
4.5 Hz, 2H), 4.00 (s, 3H), 8.10 (s, 2H); 13C NMR (DMSO-d6):
δ 41.83, 46.20, 65.33, 65.46, 57.13, 115.63, 118.20, 147.22,
159.71, 160.94. Anal. Calcd for C12H13N3O7: C, 46.31; H, 4.21;
N, 13.50. Found: C, 46.39; H, 4.13; N, 13.58.
and dried in the air to afford 1.80 g (78%) of a mixture of
2-benzylsulfonyl-6-benzylthio-4-nitrobenzamide (48a) and 2-ben-
zylsulfonyl-4-benzylthio-6-nitrobenzamid (48b) (1:1): Rf 0.36
1
(benzene-acetone 4:1); H NMR of the mixture (DMSO-d6) δ
4.25 (s, 2H), 4.40 (s, 2H), 4.78 (s, 2H), 4.82 (s, 2H), 7.15-7.45
(m, 20H in (48a ) and (48b)], 7.60 (s, 1H), 7.79 (br s, 1H), 7.90
(s, 1H), 8.10 (br s, 2H), 8.15 (s, 1H), 8.20 (br s, 1H), 8.27 (s,
1H). Anal. Calcd for C21H18N2O5S2: C, 57.00; H, 4.10; N, 6.33;
S, 14.49. Found: C, 57.16; H, 4.07; N, 6.30; S, 14.42.
4-P h en oxy-2,6-d in itr oben zoic Acid Mor p h olid e (44b).
To a solution of 2,4,6-trinitrobenzoic acid morpholide (18) (0.50
g, 1.53 mmol) in absolute DMF (5 mL) were added successively
with stirring PhOH (0.15 g, 1.59 mmol) and K2CO3 (0.22 g,
1.59 mmol). The reaction mixture was stirred at 40 °C for 24
h and poured into water (10 mL). The precipitate was filtered
off, washed with water (2 × 1 mL), air-dried, and crystallized
from an acetone-i-PrOH mixture to yield 0.54 g (94%) of
44b: mp 182-186 °C; Rf 0.20 (CCl4-acetone 4:1); 1H NMR
(DMSO-d6) δ 3.25 (t, J ) 4.5 Hz, 2H), 3.52 (t, J ) 4.5 Hz, 2H),
3.61 (t, J ) 4.5 Hz, 2H), 3.66 (t, J ) 4.5 Hz, 2H), 7.25-7.60
(m, 5H), 8.08 (s, 2H); 13C NMR (DMSO-d6) δ 41.79, 46.08,
65.26, 65.43, 118.60, 125.79, 130.57, 153.93, 119.92, 120.41,
147.23, 157.70, 160.63. Anal. Calcd for C17H15N3O7: C, 54.69;
H, 4.05; N, 11.26. Found: C, 54.73; H, 4.00; N, 11.28.
4-Azid o-2,6-d in itr oben zoic Acid Mor p h olid e (45b). To
a solution of 2,4,6-trinitrobenzoic acid morpholide (18) (0.65
g, 2.0 mmol) in absolute DMSO (3 mL) was added with stirring
NaN3 (0.13 g, 2.0 mmol). The reaction mixture was stirred at
40-60 °C for 2.5 h, poured into crushed ice (20 g). The
precipitate was filtered off, washed by water (2 × 1 mL), and
air-dried. Yield of 45b was 0.31 g (48%): mp 194-197 °C; 1H
NMR (DMSO-d6) δ 3.22 (t, J ) 4.5 Hz, 2H), 3.57 (t, J ) 4.5
Hz, 2H), 3.65 (t, J ) 4.5 Hz, 2H), 3.71 (t, J ) 4.5 Hz, 2H), 8.21
(s, 2H); MS (m/z, I) 322 (M+).
2-Ben zylt h io-4-n it r o-6-p h en oxy-N-p h en ylb en za m id e
(46a ) a n d 4-Ben zylth io-2-n itr o-6-p h en oxy-N-p h en ylben -
za m id e (46b). To a solution of 2,4-dinitro-6-phenoxy-N-
phenylbenzamide (42a ) (0.10 g, 0.26 mmol) in absolute DMF
(1 mL) were added successively with stirring PhCH2SH (0.04
g, 0.34 mmol) and K2CO3 (0.05 g, 0.36 mmol). The reaction
mixture was stirred at 20 °C for 4 h and poured into water
(10 mL). The precipitate was filtered off, washed with water
(2 × 1 mL), air-dried, and purified by TLC (silica gel, benzene,
developed three times) to yield 0.09 g (75%) of a mixture of
46a and 46b: Rf 0.07 (benzene); 1H NMR of the mixture
(DMSO-d6) δ 4.29 (s, 2H), 4.33 (s, 2H), 7.00-7.50 (m, 29H),
7.55 (d, J ) 8.0 Hz, 2H), 7.62 (d, J ) 8.0 Hz, 2H), 7.88 (s, 1H),
10.50 (br s, 2H). Anal. Calcd for C26H20N2O4S: C, 68.41; H,
4.42; N, 6.14; S, 7.02. Found: C, 68.19; H, 4.36; N, 5.95; S,
6.79.
2-Ben zylt h io-1-cya n o-4,6-d in it r ob en zen e (49a ) a n d
4-Ben zylth io-1-cya n o-2,6-d in itr oben zen e (49b). To a solu-
tion of benzylmercaptan (0.11 mL, 0.94 mmol) in DMF (1 mL)
were added successively with stirring at 15 °C K2CO3 (0.13 g,
0.94 mmol) and 1-cyano-2,4,6-trinitrobenzene15 (0.19 g, 0.80
mmol). The reaction mixture was stirred for 1 h at 15 °C and
then poured into cold water (10 mL). After 2 h of stirring the
precipitate was filtered off, washed with water (2 mL), and
air-dried. Crystallization of the solid from an i-PrOH-acetone
mixture afforded 0.23 g (91%) of a mixture of 2-benzylthio-1-
cyano-4,6-dinitrobenzene (49a ) and 4-benzylthio-1-cyano-2,6-
dinitrobenzene (49b) (3:1) as a bright-yellow powder: Rf 0.60
(CHCl3); signals of the compound (49a ) in 1H NMR of the
mixture (acetone-d6) δ 4.73 (s, 2H), 7.28-7.43 (m, 3H), 7.55
(d, J ) 7.5 Hz, 2H), 8.68 (s, 1H), 8.74 (s, 1H); signals of the
1
compound (49b) in H NMR of the mixture (acetone-d6): δ 4.67
(s, 2H), 7.28-7.55 (m, 5H), 8.50 (s, 2H). Anal. Calcd for
C
14H9N3O4S: C, 53.33; H, 2.88; N, 13.33; S, 10.17. Found: C,
53.51; H, 3.01; N, 13.18; S, 9.97.
1-Cya n o-2,4,6-tr is(ben zylth io)ben zen e (50). To a stirred
suspension of 1-cyano-2,4,6-trinitrobenzene15 (1.0 g, 4.4 mmol)
and K2CO3 (1.9 g, 14 mmol) in absolute DMF (10 mL) was
added benzylmercaptan (1.6 mL, 1.8 g, 14 mmol). The reaction
mixture was stirred at 70 °C for 2 h (during this period it
became almost colorless), cooled to 20 °C and poured into water
(∼100 mL). Organic materials were extracted with ether (5 ×
30 mL). The combined ether extracts were washed with water
(2 × 20 mL), dried over anhydrous MgSO4. The solvent was
evaporated in vacuo, hexane (10 mL) was added to the residue.
The precipitate was filtered off, washed with hexane (2 × 5
mL), and air-dried. Crystallization of the solid from i-PrOH
afforded 0.95 g (46%) of 1-cyano-2,4,6-tris(benzylthio)benzene
1
(33): mp 96-97 °C; Rf 0.72 (benzene); H NMR (DMSO-d6) δ
4.27 (s, 2H), 4.31 (s, 4H), 7.10 (s, 2H), 7.23-7.40 (m, 15H).
Anal. Calcd for C28H23NS3: C, 71.60; H, 4.94; N, 2.98; S, 20.48.
Found: C, 71.43; H, 4.99; N, 3.12; S, 20.19.
1-Cya n o-2,4,6-t r is(m et h oxyca r b on ylm et h ylt h io)b en -
zen e (51). To a stirred suspension of 1-cyano-2,4,6-trini-
trobenzene15 (1.0 g, 4.4 mmol) and K2CO3 (2.12 g, 15.3 mmol)
in absolute DMF (10 mL) was added methyl R-mercaptoacetate
(1.4 mL, 1.6 g, 15.3 mmol). The reaction mixture was stirred
at 70 °C for 2 h (during this period it became almost colorless),
cooled to 20 °C and poured into water (∼100 mL). The
precipitate was filtered off and air-dried. Crystallization from
i-PrOH afforded 1.34 g (74%) of 1-cyano-2,4,6-tris(methoxy-
carbonylmethylthio)benzene (51): mp 84-86 °C; Rf 0.25
2-Ben zylsu lfon yl-4,6-d in itr oben za m id e (47). To a solu-
tion of 2-benzylthio-4,6-dinitrobenzamide (28a ), containing
about 8% of 4-benzylthio-2,6-dinitrobenzamide (28b) (2.0 g, 6.0
mmol), in glacial AcOH (40 mL) was added 50% H2O2 (2.0 mL).
The reaction mixture was kept at 15 °C for 12 h and then
refluxed for 2 h. The solvent was evaporated in vacuo to
dryness, and the residue was washed with water (3 × 10 mL),
dried in the air, and crystallized from a i-PrOH-acetone
mixture to afford 2.0 g (91%) of 47: mp 216-219 °C; Rf 0.36
(benzene-acetone 4:1); 1H NMR (DMSO-d6) δ 4.79 (s, 2H), 7.32
(br s, 5H), 8.22 (br s, 1H), 8.40 (br s, 1H), 8.48 (s, 1H), 9.00 (s,
1H); MS (m/z, I) 365 (M+, 0.5), 91 (CH2Ph, 100). Anal. Calcd
for C14H11N3O7S: C, 46.03; H, 3.03; N, 11.50; S, 8.78. Found:
C, 46.25; H, 3.09; N, 11.32; S, 8.94.
1
(CCl4-acetone 4:1); H NMR (DMSO-d6) δ 3.72 (s, 9H), 4.02
(s, 6H), 7.21 (s, 2H). Anal. Calcd for C16H17NO6S3: C, 46.25;
H, 4.12; N, 3.37; S, 23.15. Found: C, 46.33; H, 4.09; N, 3.32;
S, 23.19.
2-Ben zylsu lfon yl-6-ben zylth io-4-n itr oben za m id e (48a )
an d 2-Ben zylsu lfon yl-4-ben zylth io-6-n itr oben zam id (48b).
Ack n ow led gm en t. The research was sponsored by
the IPP program, U.S. Department of Energy under
contract DE-AC05-00OR22725 with Oak Ridge National
Laboratory, managed and operated by UT-Battelle,
LLC.
A
mixture of 2-benzylsulfonyl-4,6-dinitrobenzamide (47)
(1.90 g, 5.20 mmol), benzylthiol (0.70 g, 0.66 mL, 5.64 mmol),
K2CO3 (0.70 g, 5.20 mmol), and absolute DMF (15 mL) was
stirred at 15 °C for 12 h and then diluted with water (50 mL).
Upon dilution, a thick oil separated that became a solid after
∼20 h. It was filtered off, washed with water (3 × 30 mL),
J O000479D