Nitroarylamines via the Vicarious Nucleophilic Substitution of Hydrogen: Amination, Alkylamination, and Arylamination of Nitroarenes with Sulfenamides

Article abstract of DOI:10.1021/jo970582b

A new reaction of sulfenamides with electrophilic arenes under basic conditions is described. The σ adducts formed from nitroarenes and the anions of sulfenamides undergo elimination of thiol to produce the corresponding o- and/or p-nitroanilines. This reaction is analogous to the known alkylation and hydroxylation of nitroarenes via the vicarious nucleophilic substitution of hydrogen (VNS). The reaction gives access to a wide range of substituted nitroanilines, nitronaphthylamines, and aminoheterocycles. By means of the reaction with N-alkyl- and N-arylsulfenamides, it is possible to obtain N-alkylnitroanilines and nitrodiarylamines. By varying the structure of sulfenamide and the reaction conditions, particularly the nature and concentration of the base, it is possible to control the orientation of animation.

Full text of DOI:10.1021/jo970582b

4878
J . Org. Chem. 1998, 63, 4878-4888
Articles
Nitr oa r yla m in es via th e Vica r iou s Nu cleop h ilic Su bstitu tion of
Hyd r ogen : Am in a tion , Alk yla m in a tion , a n d Ar yla m in a tion of
Nitr oa r en es w ith Su lfen a m id es
Mieczysław Ma¸kosza*,† and Maciej Białecki
Institute of Organic Chemistry, Polish Academy of Sciences, ul. Kasprzaka 44, 01-224 Warsaw, Poland
Received April 1, 1997 (Revised Manuscript Received J anuary 30, 1998)
A new reaction of sulfenamides with electrophilic arenes under basic conditions is described. The
σ adducts formed from nitroarenes and the anions of sulfenamides undergo elimination of thiol to
produce the corresponding o- and/or p-nitroanilines. This reaction is analogous to the known
alkylation and hydroxylation of nitroarenes via the vicarious nucleophilic substitution of hydrogen
(VNS). The reaction gives access to a wide range of substituted nitroanilines, nitronaphthylamines,
and aminoheterocycles. By means of the reaction with N-alkyl- and N-arylsulfenamides, it is
possible to obtain N-alkylnitroanilines and nitrodiarylamines. By varying the structure of
sulfenamide and the reaction conditions, particularly the nature and concentration of the base, it
is possible to control the orientation of amination.
Sch em e 1
In tr od u ction
Nitroanilines are important intermediates in organic
synthesis and industry, particularly for pharmaceuticals,
dyes, and plant protection products. There are many
methods for the introduction of amino groups into
aromatic rings, among them being the classical SNAr
displacement of halogen which is still of general use.1
Recently, there has been growing interest in the direct
nucleophilic replacement of hydrogen with the amino
group in electrophilic arenes.2 The Chichibabin reaction,
replacement of hydride anion in the reaction of electro-
philic heterocycles with sodium or potassium amides,3
was recently substantially improved and extended by use
of an external oxidant, KMnO4 in liquid ammonia.4 This
oxidative variant of the Chichibabin reaction is also
applicable to some electrophilic nitroarenes. Alterna-
tively, nitroanilines can be obtained via oxidative nu-
cleophilic amination and amidation of nitroarenes with
anilines and amides.5,6
groups X at the anionic center to nitroarenes followed
by base induced â-elimination of HX from the initially
formed σH adducts (Scheme 1). Nitrophenols can be
obtained in this way when nitroarenes are treated with
tert-butyl or cumyl hydroperoxides in the presence of a
base.
The direct amination of nitroarenes with hydroxyl-
amine in basic media, known for almost 100 years,
apparently proceeds along a similar pathway. This
reaction is, however, limited to highly electrophilic arenes
such as m-dinitrobenzene and bicyclic nitroarenes.9
There are also a few known examples of aminations with
hydroxylamine-O-sulfonic acid10 and hydrazine11 that can
be considered as examples of the VNS reaction. Some
years ago 4-amino-1,2,4-triazoles were reported to be
efficient agents for aminating nitroarenes according to
the VNS pathway.12 Recently short papers describing
base-induced amination of nitroarenes with O-methyl-
The vicarious nucleophilic substitution (VNS) reaction
offers a great potential for nucleophilic substitution of
hydrogen with carbon and oxygen groups.7,8 This process
consists of the addition of nucleophiles containing leaving
† Phone/fax: (48 22) 632 66 81. e-mail: icho-s@ichf.edu.pl.
(1) (a) Miller, J . Aromatic Nucleophilic Substitution; Elsevier:
Amsterdam, 1968. (b) Terrier, F. Nucleophilic Aromatic Displace-
ment: The Influence of the Nitro Group; VCH: New York 1991. (c)
Buncel, E.; Dust, J . M.; Terrier, F.; Chem. Rev. 1995, 95, 2261.
(2) Chupakhin, O. N.; Charushin, V. N.; van der Plas, H. C.
Nucleophilic Aromatic Substitution of Hydrogen; Academic Press: San
Diego, 1994.
(5) Esser, F.; Pook, K.-H. Synthesis 1992, 596.
(6) (a) Stern, M. K.; Cheng, B. K. J . Org. Chem. 1993, 58, 6883. (b)
Stern, M. K.; Cheng, B. K.; Hileman, F. D.; Allman, J . M. J . Org. Chem.
1994, 59, 5627.
(7) (a) Ma¸kosza, M.; Winiarski, J . Acc. Chem. Res. 1987, 20, 282.
(b) Ma¸kosza, M. Usp. Khim. 1989, 58, 1298. (c) Ma¸kosza, M. Pol. J .
Chem. 1992, 66, 3. (c) Ma¸kosza, M. Chimia 1994, 48, 499. (d) Ma¸kosza,
M.; Wojciechowski K. Liebigs Ann./ Rec. 1997, 1805.
(3) (a) Pozharskii, A. F.; Simonov, A. M.; Doron′kin, V. N. Usp. Khim.
1978, 47, 1933. (b) McGill, C. K.; Rappa, A. Adv. Heterocycl. Chem.
1988, 44, 1.
(4) (a) Woz´niak, M.; van der Plas, H. C. Croat. Chem. Acta 1986,
59, 33. (b) Chupakhin, O. N.; Charushin, V. N.; van der Plas, H. C.
Tetrahedron 1988, 44, 1. (c) Woz´niak, M.; van der Plas, H. C. Acta
Chem. Scand. 1993, 47, 95. On methylamination: Woz´niak, M.;
Grzegoz˘ ek, M. Liebigs Ann. Chem. 1993, 823.
(8) (a) Ma¸kosza, M.; Sienkiewicz, K. J . Org. Chem. 1990, 55, 4979.
(b) Mattersteig, G.; Pritzkov, W.; Voerckel, V. J . Prakt. Chem. 1990,
332, 569. (c) Sienkiewicz, K. Ph.D. Thesis, Warsaw, 1991. (d) Brose,
T.; Holzscheiter, F.; Mattersteig, G.; Pritzkov, W.; Voerckel, V. J . Prakt.
Chem. 1992, 334, 497.
S0022-3263(97)00582-3 CCC: $15.00 © 1998 American Chemical Society
Published on Web 07/07/1998

Nitroarylamines via VNS of Hydrogen
J . Org. Chem., Vol. 63, No. 15, 1998 4879
Ta ble 1. Rea ction s of Su lfen a m id es 5 a n d 8 w ith Nitr oben zen e a n d Its 2-Su bstitu ted Der iva tives
sulfenamide,
conditionsa
products of amination
(yield, %)
other products
(yield, %)
entry
arene
Z
1
2
3
4
5
6
7
8
9
10
11
12
13
1
H
5, A
8, A
8, A
8, A
5, A
8, A
5, A
8, A
8, B
8, A
8, Ac
8, A
8, A
10 (34), 11 (35)
10 (14), 11 (71)
1a
1b
1c
NO2
CN
CF3
14 (33), 15 (10)
11b (59)
10c (14), 11c (33)
11c (71)
11d (21)
11d (48)
1d
1e
F
10 (53), 16 (8)b
15 (30)
15 (78)
Cl
11e (72)
11e (60)
11f (66)
11g (39)
15 (23)
1f
1g
Br
MeO
a
b
Procedures A, B: see Experimental Section. 16: 2-(tert-Butoxy)nitrobenzene. c Procedure A with reversed order of additions.
hydroxylamine in the presence of copper salts13 and with
1,1,1-trimethylhydrazinium iodide14 were published.
that a variety of sulfenamides are efficient and versatile
reagents for aminating nitroarenes.16 Here we present
a full account of our studies on this reaction.
Taking into account our experience in VNS reactions
with carbanions and the wide possibilities connected with
this process, we attempted to design efficient and ver-
satile reagents for VNS amination. The reagents should
have the general formula NH2X where X should provide
moderate stabilization of a negative charge on the
adjacent nitrogen atom, thus facilitating its deprotona-
tion, and simultaneously X should behave as a good
leaving group in the base-induced â-elimination. For the
VNS reactions of carbanions the reagents contain such
leaving groups X as halogens, RS, or RO. Since N-
haloamines are strong oxidants and are unstable in the
presence of bases and whereas O-alkylhydroxylamines
appear to be insufficiently acidic, we have envisioned
sulfenamides RSNH2 as efficient aminating agents.
Although simple sulfenamides (R ) alkyl, phenyl) are
relatively unstable, those containing proper R such as
2-benzothiazyl, 2,4,6-trichlorophenyl, or Me2NC(S) are
sufficiently stable and are readily prepared via simple
reactions of the corresponding thiolates with ammonia
and sodium hypochlorite.15 In our preliminary com-
munication we have reported a few examples showing
Resu lts a n d Discu ssion
Selection of Su lfen a m id es. To select the most
efficient aminating agents, several representative and
synthetically available sulfenamides were synthesized.15
2-Benzothiazolesulfenamide (3), 2,4-dichlorobenzene-
sulfenamide (4), 2,4,6-trichlorobenzenesulfenamide (5),
2-pyrimidinesulfenamide (6), benzoylsulfenamide (7),
N-tetramethylenethiocarbamoylsulfenamide (8), and eth-
oxythiocarbonylsulfenamide (9) were subjected to the
reaction with nitrobenzene (1) and 1-nitronaphthalene
(2) using two sets of standard VNS conditions:7 t-BuOK/
DMF/rt (procedure A) and KOH/DMSO/rt (procedure B).
The most satisfactory yields of amination were obtained
with sulfenamides 5 and 8. The former reagent showed
a preference for ortho substitution, whereas the latter
compound reacted at the para position of the nitroarene
ring. 2-Benzothiazolesulfenamide (3) appeared to be a
useful reagent for the selective amination of 1-nitronaph-
thalene, although it was only moderately efficient in the
reaction with nitrobenzene.
(9) (a) Meisenheimer, J .; Patzig, E. Chem. Ber. 1906, 39, 2533. (b)
Baumgarten, H. E. J . Am. Chem. Soc. 1955, 77, 5109. (c) Price, C. C.;
Voong, S. T. In Organic Syntheses; Horning, E. C., Ed.; Wiley: New
York, 1955; Collect. Vol. 3, p 664. (d) Gottschlich, A.; Leverenz, K. BP
1, 127,085, 1968; Chem. Abstr. 1968, 69, 106,288. (e) Gitis, S. S.;
Pankova, N. A.; Kaminskii, A. Ya.; Kaminskaya, E. G. Zh. Org. Khim.
1969, 5, 65; Chem. Abstr. 1969, 70, 87, 178. (f) Budyka, M. F.; Terentev,
P. B.; Kost, A. N. Khim. Geterotsikl. Soed. 1977, 1554. (g) Nasielski-
Hinkens, R.; Kotel, J .; Lecloux, T.; Nasielski, J . Synth. Commun. 1989,
19, 511.
(10) Hasegawa, M.; Okamoto, T. Yakugaku Zasshi 1973, 93, 1024;
Chem. Abstr. 1973, 79, 104,485.
(11) (a) Coates, W. J .; McKillop, A. M. Heterocycles 1989, 29, 1077.
(b) Singh, B. Heterocycles 1984, 22, 1801.
(12) (a) Katritzky, A. R.; Laurenzo, K. S. J . Org. Chem. 1986, 51,
5039. (b) Katritzky, A. R.; Laurenzo, K. S. J . Org. Chem. 1988, 53,
3978.
(13) Seko, S.; Kawamura, N. J . Org. Chem. 1996, 61, 442.
(14) Pagoria, P. F.; Mitchell, A. R.; Schmidt, R. D. J . Org. Chem.
1996, 61, 2934.
Nitr oa r en es. The amination of a variety of substi-
tuted nitrobenzenes, nitronaphthalenes, and nitrohet-
(15) (a) Carr, E. L.; Smith, G. E. P., J r.; Alliger, G. J . Org. Chem.
1949, 14, 921. (b) Smith, G. E. P., J r.; Alliger, G.; Carr, E. L.; Young,
K. C. J . Org. Chem. 1949, 14, 935.
(16) (a) Ma¸kosza, M.; Białecki, M. Polish patent PL 284,896, 1990;
European Patent Application 453,885, 1991; Chem. Abstr. 1992, 116,
6403. (b) Ma¸kosza, M.; Białecki, M. J . Org. Chem. 1992, 57, 4784.

4880 J . Org. Chem., Vol. 63, No. 15, 1998
Ma¸kosza and Białecki
Ta ble 2. Rea ction s of Su lfen a m id es 5 a n d 8 w ith 4-Su bstitu ted Nitr oben zen es
products of
amination
(yield, %)
other
products
(yield %)
sulfenamide,
conditionsa
entry
arene
Z
1
2
3
4
5
6
7
8
9
10
11
12
13
17a
17b
17c
NO2
CN
CF3
5, A
5, A
5, A
5, C
5, A
5, Ac
8, A
5, A
5, Ac
8, A
8, Ac
5, A
5, A
19 (50%), 20 (8%)b
11 (11), 21 (36), 22 (5)
18b (32)
18c (35)
18c (42)
18d (35)
18d (7)
17d
17e
F
11 (31)
23 (66)
19 (84)
Cl
18e (60)
18e (57)
18e (10)
18e (4)
18f (44)
18g (63)
23 (15)
19 (37)
19 (56)
11 (29)
17f
17g
MeO
t-Bu
a
b
Procedures A, B, C: see Experimental Section. 20: 4-(tert-Butoxy)nitrobenzene. c Procedure A with reversed order of additions.
erocycles with 5 and 8 occurred smoothly to give the
expected nitroarylamines.
The results of the amination of ortho-substituted
nitrobenzenes 1a -g with sulfenamides 5 and 8 are
presented in Table 1. When 1a -g were reacted with
sulfenamide 8 under the conditions of procedure A (t-
BuOK/DMF), 4-nitroanilines 11a -g were formed exclu-
sively (entries 4, 6, 10, 12, and 13). Substitution at
position 6 was possible only with sulfenamide 5 in o-nitro-
(trifluoromethyl)benzene 1c, yielding a mixture of 4- and
6-aminated products (Table 1, entries 5 and 6). Selective
amination of 2-substituted nitroarenes at position 6 was
not achieved despite varying the reaction conditions. The
yield of the amination of o-fluoronitrobenzene (1d ) with
8 was lower than that in the other cases because of the
competing SNAr substitution of fluorine; nevertheless the
VNS reaction was the predominant process (entry 8). The
reaction of 5 with fluoronitrobenzene 1d yielded more
SNAr product (entry 7), perhaps because of the greater
tendency of reagent 5 to react at position ortho.
In contrast to the ortho-substituted nitrobenzenes, the
para-substituted nitrobenzenes 17a -g underwent ami-
nation with sulfenamide 8 in low yields (Table 2, entries
7, 10, and 11), whereas amination at position 2 with 5
proceeded satisfactorily (entries 4, 8, and 13). When
substituent Z in the aromatic ring of 17 could function
as a leaving group, the SNAr reaction became the major
competing process, but the yields of the VNS products
18d , 18e, and 18f were acceptable (entries 5, 9, and 12).
Two types of products of the SNAr reaction were iso-
lated: the “normal” products, containing the sulfenamide
moiety (19, 23), and 4-nitroaniline (11) which resulted
from cleavage of the S-N bond (Table 2, entries 5, 6, and
11). A similar phenomenon was observed in the reaction
of o-fluoronitrobenzene with 5 (Table 1, entry 7). The
mechanism of formation of these products will be dis-
cussed later.
the ortho- and para-aminated products, i.e., (25 + 27)/
26, was a function of the structure of the sulfenamide
and the reaction conditions. Amination of 3-nitroben-
zonitrile (24b) with sulfenamide 5 took place preferen-
tially at the ortho positions (Table 3, entry 3) whereas
para orientation dominated with 8 (entries 4 and 5).
There was no significant impact of the structure of the
sulfenamide on the 25/27 ratio (ortho substitution). On
the other hand, the ratio 25/27 was controlled by the type
of substituent Z, as seen in the VNS reactions with
carbanions.7 Electron-withdrawing substituents, such as
CN, COOMe, COPh, and CF3, in the position 3 direct-
edVNS substitution to position 6 to form 27 predomi-
nantly (entries 3, 6, 8, and 9), whereas Cl and MeO
directed the substitution to position 2 to form 25 (entries
12 and 16). The influence of the reaction conditions was
shown in the reaction of nitrobenzonitrile 24b with 8.
When carried out in the presence of KOH, the 4-aminated
product 26b was selectively formed (entry 5). Likewise,
EtONa increased the selectivity in amination of 24f
giving 26f (entry 10). However, when KOH was used in
In the amination of meta-substituted nitrobenzenes
24a -k with sulfenamides 5 and 8, the orientation was
a more complex problem because three isomeric products
resulting from the substitution of hydrogen at positions
2, 4, and 6 could be formed (Table 3). Distribution of

Nitroarylamines via VNS of Hydrogen
J . Org. Chem., Vol. 63, No. 15, 1998 4881
Ta ble 3. Rea ction s of Su lfen a m id es 5 a n d 8 w ith 3-Su bstitu ted Nitr oben zen es
products of amination in position (yield, %)
4
sulfenamide,
conditionsa
entry
arene
Z
2
6
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
24a
NO2
5, A
8, A
5, A
8, A
8, B
8, A
8, A
8, A
8, A
8, D
8, A
5, A
8, A
8, A
8, A
5, A
8, A
8, B
26a (44)
26a (11)
24b
CN
25b (18)
25b (5)
26b (21)
26b (59)
26b (78)
26c (20c)
26d (18)
26e (28)
26f (29)
26f (84)
26g (66)
26h (38)
26h (86)
26i (66)
26j (56)
26k (21)
26k (48)
27b (36)
27b (8)
24cb
24d
24e
24f
COOMe
COOH
COPh
CF3
27c (8)
27e (21)
27f (6)
24g
24h
F
Cl
25h (26)
25k (46)
27h (7)
24i
24j
24k
Br
Me
MeO
27k (4)
27k (12)
a
b
Procedures A, B, D: see Experimental Section. The main product (28, 40%) resulted from reaction of 8 with the carbonyl group in
24c. c Transesterification: methyl ester (26c, 15%) and tert-butyl ester (26c′, 5%).
Ta ble 4. Rea ction s of Su lfen a m id es 3, 5, a n d 8 w ith 1-Nitr on a p h th a len es
products of amination in position (yield, %)
sulfenamide,
conditionsa
other products
(yield, %)
entry
arene
Z
2
4
1
2
3
4
5
6
7
8
9
10
11
12
13
2
H
3, A
3, B
5, A
5, B
8, A
8, B
8, C
8, A
8, A
8, A
8, A
8, A
8, C
12 (71)
12 (11)
12 (63)
12 (10)
12 (61)
12 (2)
13 (6)
13 (75)
13 (11)
13 (26)
13 (24)
13 (77)
13 (16)
13a (88)
29 (<1)
29 (9)
12 (40)
30 (39)
2a
2b
2c
2d
2e
2-MeO
4-MeO
5-Br
12b (68)
12c (41)
12d (42)
12e (52)
12e (24)
13c (14)
13d (26)
13e (17)
13e (8)
31 (28)
32 (8)
33 (29)
33 (58)
5-(C3H5O2)b
5-azac
a
b
Procedures A, B, C: see Experimental Section. 2d : ethylene acetal of 1-nitro-5-naphthaldehyde. c 2e: 5-nitroquinoline.
the case of less electrophilic m-nitroanisole, no reaction
occurred (entry 18).
with sulfenamides 5 and 8 proceeded in only moderate
yield (Table 3, entries 1 and 2).
1-Nitronaphthalene (2) and its analogues 2a -f reacted
with sulfenamides even more readily than monocyclic
nitroarenes, but the amination was often accompanied
by the formation of nitrosonaphthylamines and naph-
thofurazans (Table 4). The main products in the reac-
tions of substituted 1-nitronaphthalenes with sulfen-
amides 3, 5, and 8 were 2-amino and 4-amino derivatives
12 and 13. The influence of the structure of the sulfen-
amide on the ratio of the isomeric products was much
It should be noted that the amination of dinitroarenes
with sulfenamides did not proceed satisfactorily. In the
reactions of o- and p-dinitrobenzenes 1a and 17a with 5
and 8, no expected dinitroanilines were produced. The
dominating process was SNAr substitution of the nitro
group leading to the formation of 15 and 19 or the
oxidation of the σH adduct leading to 14 (Tables 2 and 3,
entries 1). These results are in accordance with the
known difficulties in achieving VNS in o- and p-dini-
trobenzenes.17 m-Dinitrobenzene is known to be a very
active partner in the VNS reaction,18 but its amination
(17) Ma¸kosza, M.; Golin´ski, J . Baran, J . J . Org. Chem. 1984, 49,
1488.
(18) Ma¸kosza, M.; Ludwiczak, S. J . Org. Chem. 1984, 49, 4562.

4882 J . Org. Chem., Vol. 63, No. 15, 1998
Ta ble 5. Rea ction s of N-Su bstitu ted Su lfen a m id es w ith Nitr oa r en es
Ma¸kosza and Białecki
sulfenamide,
conditionsa
products
(yield %)
entry
arene
Z
R
R′
1
2
3
4
5
6
7
8
9
1c
1e
24b
24h
2-CF3
2-Cl
3-CN
3-Cl
44, A
42, A
44, Ac
44, Ac
44a , Cc
42, A
44a , Cc
42, A
43, A
44, B
Ph
Ph
45a (33)
45b (46)
45c (45)
45d (52)
45e (69)
45f (66)
45g (33)
(96) e
C4H8NCSb
cyclohexyl
Ph
Ph
4-MeO-C6H4
cyclohexyl
4-MeO-C6H4
cyclohexyl
Ph
Ph
Ph
Ph
24i
24k
2
3-Br
C4H8NCSb
Ph
3-MeO
d
C4H4
C4H8NCSb
C4H8NCSb
Ph
45j (19)
45j (61)
10
Ph
a
b
Procedures A, B, C: see Experimental Section. N,N-Tetramethylenethiocarbamoil. c Conditions modified, see Experimental Section.
1-Nitronaphthalene. e Total yield of two isomers: N-cyclohexyl-1-nitro-2-naphthylamine (45h , 70%) and N-cyclohexyl-1-nitro-4-
d
naphthylamine (45i, 26%).
weaker here than in the case of nitrobenzenes but an
increasing tendency for para substitution in the order 3,
5, and 8 was retained (Table 4, entries 1, 3, and 5). On
the other hand, the effect of the reaction conditions on
distribution of the 2- and 4-isomers was much stronger
than that in the case of nitrobenzenes. The effect of the
change of the base concentration was particularly evident
in the reactions with 2-benzothiazolesulfenamide (3).
This compound was not an effective aminating agent for
mononitrobenzenes but reacted efficiently with nitronaph-
thalenes yielding mainly the 2-amino product 12 in the
presence of t-BuOK/DMF whereas the 4-amino isomer
13 was formed predominantly when KOH/DMSO was
used (Table 4, entries 1 and 2).
The amination of 2-nitronaphthalene (34) with 8 gave
2-nitro-1-naphthylamine (35) in 94% yield. This orienta-
tion was in agreement with all previous observations and
mechanistic concepts indicating that position 1 in 2-ni-
tronaphthalene is the most active toward nucleophilic
attack.7
explained in case of the carbanionic VNS reaction in
terms of conjugation between the alkoxy and nitro
groups.21 Amination of 3-nitrothiophene (38a ) gave the
2-amino derivative 39a (23%) and similarly, the reaction
with 1-methyl-4-nitroimidazole (38b) led to 39b (36%).
In cases where the heterocyclic ring was fused with a
nitrobenzene ring, the reaction with 8 took place in the
ring substituted with the nitro group. Amination of
5-nitroquinoline (2e) gave a mixture of nitro- and ni-
trosoaminoquinolines (Table 4, entries 12 and 13). 6-Ni-
troquinoline (34a ) yielded the 5-amino derivative 35a
(98%), behaving analogously to 2-nitronaphthalene. 1,2-
Dimethyl-5-nitroindole (40) underwent amination in the
benzene ring giving 41 in moderate yield (45%), as could
be expected for a less electrophilic nitroarene.
These results indicate that the reaction of carbo- and
heterocyclic nitroarenes with sulfenamides 5 and 8 is an
efficient method of synthesis of nitroarylamines via direct
introduction of the amino group.
Alk yl- a n d Ar yla m in a tion . N-Alkyl-substituted sul-
fenamides are readily available via oxidation of mixtures
of thiols and primary amines, whereas N-aryl derivatives
can be simply prepared via reaction of phenylsulfenyl
chlorides with anilines.
N′-Cyclohexyl-N,N-tetramethylenethiocarbamoylsul-
fenamide (42), an N-alkyl derivative of the most efficient
aminating agent 8, reacted with substituted nitroben-
zenes along the VNS amination pathway, yielding the
corresponding N-cyclohexyl-4-nitroanilines (Table 5, en-
tries 2 and 6). Also, the reaction of 42 with 1-nitronaph-
thalene gave the expected products of N-alkylamination
(Table 5, entry 8). Despite the bulkiness of the N-
cyclohexyl group which should increase steric hindrance,
the ratio of the products of the reaction of 2 with 42 was
almost identical to that observed in the reaction with 5
or 8 (cf., Table 4, entries 3 and 5). The results in Table
5 show that the reaction with N-alkyl sulfenamides is
an efficient method of synthesis of alkylarylamines.
Amination of five- and six-membered heterocyclic
compounds with sulfenamide 8 proceeded satisfactorily
and similarly to VNS alkylation.19,20 Orientation of the
substitution corresponded to that reported for VNS with
carbanions. â-Nitropyridines were aminated at positions
activated by the nitro group: 4-ethoxy-3-nitropyridine
(36a ) and 2-methoxy-5-nitropyridine (36b ) yielded the
expected amino derivatives 37a (75%) and 37b (42%).
(19) (a) Ma¸kosza, M. Synthesis 1991, 103. (b) Ma¸kosza, M.; Kwast,
E. Tetrahedron 1995, 51, 8339.
(20) (a) Ma¸kosza, M.; Chylin´ska, B.; Mudryk, B. Liebigs Ann. Chem.
1984, 8. (b) Ma¸kosza, M.; Sienkiewicz, K.; Wojciechowski, K. Synthesis
1990, 850.
The orientation pattern in these pyridine derivatives was
(21) Ma¸kosza, M.; Owczarczyk, Z. J . Org. Chem. 1989, 54, 5094.

Nitroarylamines via VNS of Hydrogen
J . Org. Chem., Vol. 63, No. 15, 1998 4883
Sch em e 2
Sch em e 3
Arylamination with N-aryl sulfenamides posed some
problems (Table 5) because an aryl substituent at the
nitrogen diminished the nucleophilicity of the sulfen-
amide anion dramatically. The reaction of 1-nitronaph-
thalene with N,N-tetramethylenethiocarbamoylsulfen-
anilide (43) yielded the desired naphthylphenylamine 45j
in rather low yield (Table 5, entry 9). This problem was
solved by using less acidic benzenesulfenanilides
PhSNHAr where Ar ) Ph (44) and p-MeO-C6H4 (44a ).
These sulfenamides were prepared via the reaction of
benzenesulfenyl chloride PhSCl with aniline and p-
anisidine.22 The reaction of 44 with several nitroarenes
yielded the expected diarylamines (Table 5, entries 1, 3,
and 4). Compound 44a was more desirable for arylami-
nation of less electrophilic arenes such as 3-nitroanisole
(24k ), because of expected higher nucleophilicity of anion
of 44a . Thus 24k which had not been efficiently ami-
nated with 44 reacted satisfactorily with 44a (Table 5,
entry 7).
The VNS arylamination of substituted nitrobenzenes
always occurred at position 4 (Table 5, entries 1, 3, 4, 5,
and 7). This orientation is apparently due to the moder-
ate nucleophilicity of the sulfenanilides which should
promote formation of the thermodynamically controlled
products (see the discussion below). The exception from
this orientation pattern was 2-nitrothiophene (46) which
in the reaction with 44 gave two isomers 47a and 47b
(Scheme 2). The tendency for formation of the 4-substi-
tuted products in the arylamination of nitroarenes was
enhanced when the reaction was carried out in KOH/
DMSO (Table 5, entry 10), a result similar to that seen
in the reactions with 5 and 8.
Mech a n ism . Although stoichiometry of the amination
of nitroarenes with sulfenamides is analogous to the VNS
alkylation and hydroxylation, its mechanistic features
should be clarified independently. Existing data indicate
that the VNS reactions with carbanions containing
leaving groups X and with anions of alkyl hydroperoxides
proceed via addition of these nucleophiles to nitroarenes
with the formation of σH adducts followed by base induced
â-elimination of HX or ROH. The elimination process
gives nitrobenzylic carbanions or nitrophenolates which
are protonated during the workup procedure.
Amination with sulfenamides is stoichiometrically
similar to the amination with hydroxylamine. Although
the latter process has been known for a long time, there
is only one report on mechanistic studies of this reaction.
Gitis and co-workers23 proposed that the initial σH
adducts were converted into the amination products via
departure of OH anions with simultaneous intramolecu-
lar 1,2-hydride shift from the ring sp3 carbon atom to the
nitrogen, leading directly to the nitroaniline. They
confirmed this hypothesis by amination of perdeuterio
m-dinitrobenzene with hydroxylamine in methanolic
NaOH solution. Since the MS measurement indicated
that the product contained five deuterium atoms (i.e., did
not lose deuterium), the authors concluded that the
reaction occurred via the 1,2-hydride shift.
In our opinion, those experiments cannot be considered
as sufficiently diagnostic. The amino group in 2,4-
dinitroaniline produced in the reaction is a strong NH-
acid, and it should undergo fast proton exchange under
the reaction conditions, so there is no reason to look for
the deuterium in the amino group. We confirmed this
in independent experiments in which 2,4-dinitroaniline
underwent rapid N-deuteriation in NaOH/D2O solution
and vice versa: N-deuterated aniline lost deuterium when
treated with NaOH/H2O. Moreover, mass spectrometry
is not a reliable tool to measure deuterium content in
groups possessing labile protons, such as NH2 in nitro-
anilines, because traces of water in the ionizing chamber
could strongly affect the result. In conclusion, the
experimental verification of the 1,2-hydride shift mech-
anism by Gitis is in our opinion invalid.
Possible mechanistic patterns for substitution of hy-
drogen and halogen in nitroarenes with sulfenamides are
presented in Scheme 3. The first question is whether
the σH adducts A are formed via path i or ii. Since the
â-elimination of RSH from σH adducts requires strong
base which can deprotonate the starting sulfenamide, a
direct differentiation between paths i and ii cannot be
made. The differentiation was made using SNAr of
fluorine in p-fluoronitrobenzene as the model process.
The substitution of fluorine proceeds via anionic σF
adducts B which can be formed in two ways (paths iii
and iv) that are analogous to paths ii and i in the σH
adduct formation. Path iii can operate only when a base
sufficiently strong for deprotonation of RSNH2 to RSNH-
is used, whereas formation of σF adduct B via path iv is
possible in the presence of a much weaker base, e.g.,
triethylamine, which is able to deprotonate the much
more acidic dipolar adduct C. It was found that the
(22) Lecher, H. Chem. Ber. 1925, 58, 409.
(23) Gitis, S. S.; Glaz, A. I.; Grigorev, V. V.; Kaminskii, A. Ya.;
Martynenko, A. S.; Saukov, P. I. Zh. Org. Khim. 1967, 3, 1617; Chem.
Abstr. 1968, 68, 12,104.

4884 J . Org. Chem., Vol. 63, No. 15, 1998
Ma¸kosza and Białecki
reaction of p-fluoronitrobenzene with sulfenamide 8 did
proceed in the presence of t-BuOK (Table 2, entry 7) and
did not in the presence of Et3N, so one can conclude that
the substitution of fluorine occurred via path iii, namely,
by addition of the sulfenamide anion followed by depar-
ture of F- anion and that sulfenamide itself does not add
to p-fluoronitrobenzene with formation of the dipolar σF
adducts C. It is thus reasonable to assume that the
formation of the anionic σH adducts proceeds via path ii
rather than via path i.
The second question is how the σH adducts are con-
verted into the VNS products. Since the reaction of
R-halo carbanions and alkyl hydroperoxide anions pro-
ceed via base-induced â-elimination of HX from the σH
adducts, the same pathway was expected here. The rate
of such â-elimination depends on the base strength and
concentration; thus the effect of the base on the rate of
the process was studied using competition between
SNAr of halogen and VNS in o- and p-halonitrobenzenes.
of the substrates, a mixture of 11e and the SNAr product
15 was formed (entry 9).
The changes of the VNS/SNAr ratio in the reactions of
halonitroarenes with sulfenamides indicated that in the
case of hydrogen substitution (ii, Scheme 3), contrary to
the halogen substitution (path iii), the rate of conversion
of the σH adduct depended on the strength and concen-
tration of the base. This conclusion strongly supports
the hypothesis that the mechanism of the reaction
includes base-promoted â-elimination, and this is con-
sistent with the previous studies on the mechanisms of
the VNS alkylation24 and hydroxylation.8
Or ien ta tion . This mechanistic picture of the VNS
amination of nitroarenes with sulfenamides coming from
the studies of the competition between SNAr of halogen
and VNS of hydrogen was fully confirmed by the observed
effect of the reaction conditions on the orientation of VNS.
Numerous examples of the VNS amination presented in
this paper indicate that its orientation is governed by
three factors: the reaction conditions, structure of the
sulfenamide, and substituents in the aromatic ring.
The influence of the reaction conditions was particu-
larly notable in the case of the amination of 1-nitronaph-
thalene (2), which, independent of the structure of the
sulfenamide, gave mostly the 2-amino derivative 12 in
the presence of t-BuOK/DMF (Table 4, entries 1, 3, and
5) and the 4-amino derivative 13 when KOH/DMSO was
used (Table 4, entries 2, 4, and 6). This effect of the type
of the base on the orientation is analogous to that
observed for the VNS hydroxylation of 1-nitronaphtha-
lene with tert-butyl and cumyl hydroperoxides8 and can
be rationalized in a similar way. At a high concentration
of the strong, soluble base (t-BuOK/DMF) the fast
â-elimination of RSH from the σH adduct took place; thus
the equilibration between the isomeric σH adducts at
positions 2 and 4 was prevented. Since under these
conditions the highly predominant product was the
2-amino isomer, one can conclude that the initial addition
of the anion of 5 occurs at position 2. On the other hand,
when the base was insoluble (KOH/DMSO) or it was
present in a low concentration, elimination became
slower and the system could equilibrate in favor of the
more stable σH adduct leading to the 4-substituted
product. Thus, 1-nitro-2-naphthylamine formed in the
reaction with 3 or 5 in t-BuOK/DMF system was the
product of kinetic control whereas 1-nitro-4-naphthyl-
amine obtained in the reaction of 2 with 8 under KOH/
DMSO conditions was the product of thermodynamic
control. These reactions of amination of 1-nitronaphtha-
lene can be considered as textbook examples of kinetic
and thermodynamic control.
In 4-fluoronitrobenzene (17d ) there are two positions
susceptible to a nucleophilic attack in the ring: position
4, which is occupied by fluorine, and position 2, occupied
by hydrogen. Therefore two reactions with the sulfen-
amide anion could occur: VNS of the hydrogen leading
to 18d and SNAr of the fluorine leading to 23 (Scheme
3). A competition between these reactions was indeed
observed. The ratio of the products formed depended on
the reaction conditions. When an excess of base in high
concentration was present in the reaction mixture (t-
BuOK in DMF), the arene 17d reacted with the sulfen-
amide 5 yielding 18d along with 4-nitroaniline (11), the
SNAr product (Table 2, entry 5). When a low concentra-
tion of the base was maintained (t-BuOK/DMF slowly
added to a solution of the substrates), the yield of the
VNS product 18d was diminished and fluorine substitu-
tion leading to 23 dominated (entry 6). These results
showed that a high base concentration increased the rate
of the VNS reaction.
Analogously, the reaction of sulfenamide 5 with 4-chlo-
ronitrobenzene (17e), in which SNAr of halogen proceeds
slower than that in 17d , gave selectively the VNS
amination product 18e under t-BuOK/DMF conditions
(Table 2, entry 8). When the base was added continu-
ously to the substrates, so its concentration was low
throughout the reaction time, a mixture of 18e and the
SNAr product 23 was formed (entry 9). The reaction with
sulfenamide 8 in the t-BuOK/DMF system yielded the
VNS product 18e and the SNAr product 19 (Table 2, entry
10). When the base was added slowly over the course of
the reaction, a proportion of 19 increased (entry 11).
The results of competition between the substitution of
hydrogen and the substitution of halogen were even more
convincing for 2-halonitrobenzenes. We reported previ-
ously the results of the reaction of 2-fluoronitrobenzene
(1d ) with the sulfenamide 8.16 Under conditions A (t-
BuOK/DMF) the formation of the VNS product 11d
dominated (Table 1, entry 8). When insoluble KOH was
used as the base, the exclusive product was 15, coming
from SNAr (entry 7). In the case of 2-chloronitrobenzene
(1e) there was a similar effect, although shifted toward
the VNS, due to the lower susceptibility of chlorine to
nucleophilic substitution. The reaction of 1e with the
sulfenamide 8 and an excess of base yielded exclusively
the VNS product 11e (Table 1, entry 10). When a
solution of t-BuOK in DMF was slowly added to a solution
The orientation of the amination also depended on the
type of aminating agent. Less acidic sulfenamides such
as 3 and 5 led to preferential formation of the 2-amino
isomer and sulfenamide 8, which is probably more acidic
so its anion is less nucleophilic than 3 and 5, introduced
the amino group into the para position.
Byp r od u cts. The intriguing formation of 2- and
4-nitroanilines 10 and 11 in the reactions of compound
5 with 2- and 4-substituted nitrobenzenes 1d , 17b, 17d ,
and 17f (Table 1, entry 7, and Table 2, entries 2, 5, and
12) poses a question: in which way was the N-S bond
broken so that simple nitroanilines were formed instead
(24) Ma¸kosza, M.; Glinka, T. J . Org. Chem. 1983, 48, 3860.

Nitroarylamines via VNS of Hydrogen
J . Org. Chem., Vol. 63, No. 15, 1998 4885
was added to ammonia (25% solution in water, 13 mL) to which
sodium hypochlorite (1 N solution in water, 55 mL) had been
previously added slowly enough to maintain the temperature
below 0 °C. The mixture was stirred vigorously for 30 min,
and then the pure sulfenamide was filtered off. 3 was obtained
from 2-mercaptobenzothiazole: mp 119-120 °C; lit.15 mp 127-
128 °C. 4 from 2,4-dichlorothiophenol: mp 56-60 °C. Anal.
Calcd for C6H5Cl2NS: C, 37.13; H, 2.60; N, 7.22. Found: C,
37.11; H, 2.63; N, 7.44. 5 from 2,4,6-trichlorothiophenol: mp
90-93 °C; lit.28 mp 91-92 °C. 6 from 2-mercaptopyrimidine:
mp 115-116 °C; lit.29 mp 110-112 °C. 7 from thiobenzoic
acid: mp 86-89 °C; lit.30 mp 88.5-90 °C. 8 from ammonium
N,N-tetramethylenedithiocarbamate: mp 84.5-85 °C.31 Anal.
Calcd for C5H10N2S2: C, 37.01; H, 6.21; N, 17.26. Found: C,
36.96; H, 6.09; N, 17.14. 9 from O-ethyl xanthate: oil.32 Anal.
Calcd for C3H7NOS2: C, 26.26; H, 5.14; N, 10.21. Found: C,
25.91; H, 5.42; N, 9.79.
N′-Cyclohexyl-N,N-tetramethylenethiocarbamoylsulfen-
amide 42 was obtained by reaction of sodium N,N-tetrameth-
ylenedithiocarbamate with cyclohexylamine and iodine:15 mp
59-61 °C; lit.33 mp 65 °C. N,N-Tetramethylenethiocarbam-
oylsulfenanilide 43 was obtained by reaction of N,N-tetra-
methylenethiocarbamoyl disulfide with aniline catalyzed by
silver nitrate:34 mp 80-85 °C. Anal. Calcd for C11H14N2S2:
C, 55.43; H, 5.92; N, 11.75. Found: C, 56.11; H, 6.25; N, 11.15.
The sulfenanilides 44 and 44a were obtained from benzene-
sulfenyl chloride and the respective aniline.22 44 from
aniline: mp 52-55 °C; lit.22 mp 53-55 °C. 44a from p-
anisidine: mp 60-64 °C; lit.35 mp 69-70 °C. 2,4,6-Trichloro-
4′-nitrobenzenesulfenanilide was obtained from 2,4,6-trichlo-
robenzenesulfenyl chloride and 4-nitroaniline36 and proved to
be identical with 23 by TLC and NMR.
Sch em e 4
of the expected SNAr products N-(nitroaryl)sulfenamide
23 and its ortho isomer?
Compound 23, synthesized by an alternate route, was
stable under the reaction conditions and did not convert
into 11. Thus, the formation of nitroaniline 11 did not
result from the decomposition of N-(nitroaryl)sulfenamide
23 and the S-N bond must thus have been cleaved in
an earlier reaction step. The substitution of the cyano
group in 4-nitrobenzonitrile 17b is even more intriguing
(Table 2, entry 2) because nucleophilic substitution of CN
in a benzene ring is quite unusual.
Other interesting byproducts were 1-nitroso-2-naph-
thylamines (30 and 31) and naphthofurazans (29 and 32).
The formation of naphthofurazans was observed earlier
by Hasegawa10,25 and by Nasielski-Hinkens26 in their
studies on amination of nitronaphthalenes and nitro-
quinolines with hydroxylamine and hydroxylamine-O-
sulfonic acid. Formation of the same byproducts in those
reactions justifies the supposition that the amination
with sulfenamides and the amination with hydroxyl-
amine proceed according to similar mechanisms.
Since few reactions of sulfenamide anions have been
reported, one further example of nucleophilic reaction of
RSNH- should be pointed out here: compound 8 reacts
with methyl 3-nitrobenzoate 21c to give mainly the
N-acyl product 28 (Table 3, entry 6).
Nitroarenes were commercially available or prepared ac-
cording to the described procedures: 5-bromo-1-nitronaphtha-
lene (2c),37 5-{2-(1,3-dioxolanyl)}-1-nitronaphthalene (2d ),38
4-tert-butylnitrobenzene (17g),39 4-ethoxy-3-nitropyridine (36a),40
3-nitrothiophene (38a ),41 1-methyl-4-nitroimidazole (38b),42
1,2-dimethyl-5-nitroindole (40).43
Con clu sion s
Rea ction s of Nitr oa r en es w ith Su lfen a m id es. The
yields were not optimized. A. Nitroarene (2 mmol) and
sulfenamide (2 mmol) dissolved in DMF (2 mL) were added
dropwise, during 5 min, to a solution of t-BuOK (0.56 g, 5
mmol) in DMF (6 mL) at 20 °C. Stirring was continued for 15
min, and the mixture was poured into cold water (50 mL).
Extraction with CH2Cl2, washing with water, drying with
Na2SO4, and chromatography yielded products as yellow or
orange crystals. Mod ifica tion s. 45c (Table 5, entry 3): temp
-25 °C. 45d (Table 5, entry 4): temp -35 °C, stirring for 2
h. 47a -b (Scheme 2): temp -25 °C, stirring for 5 min.
The vicarious nucleophilic substitution of hydrogen in
nitroarenes with sulfenamides under basic conditions
provides a new general way for synthesis of nitroanilines.
Sulfenamide 8 is an efficient aminating agent in the
synthesis of substituted p-nitroanilines, 1-nitro-4-naph-
thylamines, and aminoheterocycles. Introduction of the
amino substituent at the position ortho to the nitro group
is possible with sulfenamides 3 and 5, 3 being preferred
in the case of 1-nitronaphthalenes. Also, the new reac-
tion offers opportunities of introduction of alkylamino and
arylamino substituents into nitroarene rings.
B. Nitroarene (2 mmol) and sulfenamide (2 mmol) dissolved
in DMSO (2 mL) were added dropwise, during 5 min, to an
intensively stirred suspension of powdered KOH (85%, 0.66
The simplicity of the procedure and easy recycling of
the aminating agent (Scheme 4) makes amination with
sulfenamides an attractive method even for large scale
preparations, because the only consumable reagents in
the process are ammonia and sodium hypochlorite. If a
method for the non-chlorine production of sulfenamides
is found, the VNS amination can help avoid the use of
chlorine in the manufacture of nitroanilines which are
now obtained mainly via chloronitroarenes.6
(28) Zhmurowa, I. N.; Martynyuk, A. P.; Kirsanov, A. V. Zh. Obsh.
Khim. 1967, 37, 1879; Chem. Abstr. 1968, 68, 28 781.
(29) Hurley, T. J .; Robinson, M. A. J . Med. Chem. 1965, 8, 888.
(30) Raasch, M. S. J . Org. Chem. 1972, 37, 3820.
(31) Yonemoto, K.; Shibuya, I.; Honda, K. Bull. Chem. Soc. J pn
1988, 61, 2232 (mp not reported).
(32) Go¨sl, R. Angew. Chem., Int. Ed. Engl. 1962, 1, 268.
(33) Faid-Allah, H. M. Rev. Roum. Chim. 1988, 33, 815.
(34) Davis, F. A.; Friedman, A. J .; Kluger, E. W.; Skibo, E. B.; Fretz,
E. R.; Milicia, A. P.; Le Masters, W. C.; Bentley, M. D.; Lacadie, J . A.;
Douglas, I. B. J . Org. Chem. 1977, 42, 967.
Exp er im en ta l Section 27
(35) Miura, Y.; Kinoshita, M. Bull. Chem. Soc. J pn 1977, 50, 1142.
(36) Sandler, S. R.; Karo, W. Organic Functional Group Prepara-
tions; Academic Press: New York, 1989; Vol. 3, pp 162-205.
(37) Lock, G. Monatsh. Chem. 1950, 81, 850.
(38) Ma¸kosza, M.; Danikiewicz, W.; Wojciechowski, K. Liebigs Ann.
Chem. 1987, 711.
Rea gen ts. General procedure for synthesis of sulfenamides
3-9.15 The sodium salt of the thiol derivative, RSNa, (50
mmol), was dissolved in water (50 mL) and filtered. Then it
(39) Shoesmith, J . B.; Mackie, A. J . J . Chem. Soc. 1928, 2334.
(40) Bijlsma, U. G.; den Hertog, H. J . Recl. Trav. Chim. Pays-Bas
1956, 75, 1187.
(41) Steinkopf, W.; Ho¨pner, T. Liebigs Ann. Chem. 1933, 501, 174.
(42) Grimison, A.; Ridd, J . H.; Smith, B. V. J . Chem. Soc. 1960, 1357.
(43) Noland, W. E.; Smith, L. R.; J ohnson, D. C. J . Org. Chem. 1963,
28, 2262.
(25) Hasegawa, M.; Okamoto, T. Yakugaku Zasshi 1973, 93, 1019;
Chem. Abstr. 1973, 79, 105 052.
(26) Nasielski-Hinkens, R.; Faucon, F.; Owen, J . P. Bull. Soc. Chim.
Belg. 1984, 93, 953.
(27) For general directions, see: Ma¸kosza, M.; Stalewski, J . Tetra-
hedron 1995, 51, 7263.

4886 J . Org. Chem., Vol. 63, No. 15, 1998
Ma¸kosza and Białecki
g, 10 mmol) in DMSO (6 mL) at 20 °C. Stirring was continued
for 55 min and followed by workup as in A.
(d, J ) 9.4, 1H), 8.45 (d, J ) 9.4, 1H). Anal. Calcd for C12H9-
BrN2O3: C, 46.63; H, 2.93; N, 9.06. Found: C, 46.84; H, 3.11;
N, 9.32.
C. Nitroarene (2 mmol) and sulfenamide (2 mmol) dissolved
in DMF (2 mL) were added dropwise, during 5 min, to a
solution of t-BuOK (0.56 g, 5 mmol) in liquid ammonia (ca. 6
mL). Stirring was continued for 55 min, and then the
ammonia was evaporated. Water (50 mL) was added followed
by workup as in A. Modifications: 41e and 41g (Table 5,
entries 5 and 7): stirring for 3 h.
6-Am in o-5-n it r o-1-n a p h t h a ld eh yd e et h ylen e a cet a l
(12d ): mp 159-161 °C; 1H NMR δ 4.13 (m, 4H), 6.30 (s, 1H),
7.26 (d, J ) 9.5, 1H), 7.59 (m, AB portion of ABX system, J )
7.4, 6.9, 1.1, 2H), 8.25 (d, J ) 9.5, 1H), 8.46 (m, X portion of
ABX system, J ) 6.9, 1.1, 1H). Anal. Calcd for C13H12N2O4:
C, 60.00; H, 4.65; N, 10.76. Found: C, 59.92; H, 4.71; N, 10.56.
5-Nitr o-6-a m in oqu in olin e (12e): mp 173-175 °C; lit.44
mp 178 °C; 1H NMR δ 7.50 (d, J ) 9.4, 1H), 7.58 (dd, J ) 8.8,
4.3, 1H), 7.98 (d, J ) 9.4, 1H), 8.67 (dd, J ) 4.3, 1.5, 1H), 9.01
(dm, J ) 8.8, 1H).
D. Nitroarene (2 mmol) and sulfenamide (2 mmol) dissolved
in DMF (2 mL) were added dropwise, during 5 min, to an
intensively stirred suspension of EtONa (0.41 g, 6 mmol), in
liquid ammonia (ca. 6 mL). Stirring was continued for 35 min
followed by workup as in C.
1-Nitr o-4-n a p h th yla m in e (13): mp 190-192 °C; lit.44 mp
195 °C; 1H NMR δ 6.83 (d, J ) 8.8, 1H), 7.57 (m, 1H), 7.76 (m,
1H), 8.29 (d, J ) 8.5, 1H), 8.40 (d, J ) 8.8, 1H), 8.88 (dm, J )
8.8, 1H).
Nitr oa r yla m in es. The 1H NMR data were taken at 200
MHz in acetone-d6 if not indicated otherwise. Coupling
constants J are given in hertz. The signals of NH and NH2
are not included as their chemical shifts vary over a wide
range.
3-Meth oxy-1-n itr o-4-n a p h th yla m in e (13a ): mp 162-163
°C; 1H NMR δ 3.95 (s, 3H), 6.73 (s, 1H), 7.37 (m, 1H), 7.59 (m,
1H), 7.74 (m, 1H), 8.13 (m, 1H). Anal. Calcd for C11H10N2O3:
C, 60.55; H, 4.62; N, 12.84. Found: C, 60.56; H, 4.59; N, 12.91.
8-Br om o-1-n itr o-4-n a p h th yla m in e (13c): 1H NMR (DM-
SO-d6, mixture with 12c) δ 6.84 (d, J ) 9.1, 1H), 7.53 (dd, J )
8.9, 7.5, 1H), 7.83 (dd, J ) 7.5, 1.2, 1H), 8.31 (d, J ) 9.1, 1H),
8.81 (dd, J ) 8.9, 1.2, 1H). Isolated as N-acetyl derivative:
mp 188-190 °C; 1H NMR δ 2.27 (s, 3H), 7.63 (dd, J ) 8.7, 7.5,
1H), 8.05 (m, 1H), 8.07 (dd, J ) 7.5, 1.1, 1H), 8.27 (d, J ) 8.4,
1H), 8.38 (dd, J ) 8.7, 1.1, 1H). Anal. Calcd for C12H9-
BrN2O3: C, 46.63; H, 2.93; N, 9.06. Found: C, 47.22; H, 3.21;
N, 9.00.
8-Am in o-5-n itr on a p h th a ld eh yd e eth ylen e a ceta l (13d ):
mp 144-146 °C; 1H NMR δ 4.26 (m, 4H), 6.63 (s, 1H), 6.88 (d,
J ) 8.8, 1H), 7.69 (dd, J ) 8.8, 7.4, 1H), 7.97 (dd, J ) 7.4, 1.0,
1H), 8.24 (d, J ) 8.8, 1H), 8.82 (dd, J ) 8.8, 1.0, 1H). Anal.
Calcd for C13H12N2O4: C, 60.00; H, 4.65; N, 10.76. Found: C,
59.77; H, 4.57; N, 10.51.
2-Nitr oa n ilin e (10): mp 69-71 °C; lit.44 mp 70 °C; 1H NMR
δ 6.68 (m, 1H), 7.07 (dd, J ) 8.6, 1.3, 1H), 7.41 (m, 1H), 8.04
(dd, J ) 8.7, 1.5, 1H).
2-Nitr o-3-tr iflu or om eth yla n ilin e (10c): mp 59-62 °C;
lit.44 mp 63-65 °C; 1H NMR δ 7.10 (dm, J ) 7.5, 1H), 7.34
(dm, J ) 8.5, 1H), 7.50 (m, 1H).
4-Nitr oa n ilin e (11): mp 147-149 °C; lit.44 mp 148 °C; 1H
NMR δ 6.75 (m, AA′ portion of AA′XX′ system, 2H), 8.00 (m,
XX′ portion of AA′XX′ system, 2H).
3-Am in o-6-n itr oben zon itr ile (11b): mp 189-191 °C; lit.44
1
mp 190-191 °C; H NMR δ 7.03 (dd, J ) 9.2, 2.6, 1H), 7.16
(d, J ) 2.6, 1H), 8.16 (d, J ) 9.2, 1H).
4-Nitr o-3-tr iflu or om eth yla n ilin e (11c): mp 125-127 °C;
1
lit.44 mp 129-130 °C; H NMR δ 6.94 (dd, J ) 9.0, 2.6, 1H),
7.14 (d, J ) 2.6, 1H), 7.97 (d, J ) 9.0, 1H).
3-F lu or o-4-n itr oa n ilin e (11d ): mp 159-161 °C; lit.44 mp
161 °C; 1H NMR (500 MHz) δ 6.52 (dd, J ) 14.3, 2.4, 1H), 6.57
(ddd, J ) 9.1, 2.4, 0.6, 1H), 7.92 (m, 1H).
5-Nitr o-8-a m in oqu in olin e (13e): mp 195-197 °C; lit.44
mp 197 °C; 1H NMR δ 6.97 (d, J ) 9.0, 1H), 7.78 (dd, J ) 8.9,
4.1, 1H), 8.50 (d, J ) 9.0, 1H), 8.85 (dd, J ) 4.1, 1.6, 1H), 9.35
(dd, J ) 8.9, 1.6, 1H).
3,4-Din itr o-N-(N,N-tetr am eth ylen eth iocar bam oylth io)-
a n ilin e (14): mp 173 °C (dec); 1H NMR δ 1.92-2.25 (m, 4H)
3.73 (t, J ) 6.9, 2H), 3.81 (t, J ) 7.0, 2H), 7.39 (dd, J ) 9.0,
2.5, 1H), 7.46 (d, J ) 2.5, 1H), 8.10 (d, J ) 9.0, 1H). Anal.
Calcd for C11H12N4O4S2: C, 40.24; H, 3.68; N, 17.06. Found:
C, 40.25; H, 3.58; N, 16.95.
3-Ch lor o-4-n itr oa n ilin e (11e): mp 156-159 °C; lit.44 mp
158 °C; 1H NMR δ 6.72 (dd, J ) 9.0, 2.4, 1H), 6.84 (d, J ) 2.4,
1H), 7.95 (d, J ) 9.0, 1H).
3-Br om o-4-n itr oa n ilin e (11f): mp 170-172 °C, lit.44 mp
1
176-178 °C; H NMR δ 6.74 (dd, J ) 9.0, 2.4, 1H), 7.05 (d, J
) 2.4, 1H), 7.93 (d, J ) 9.0, 1H).
3-Meth oxy-4-n itr oa n ilin e {11g): mp 158-160 °C; lit.44 mp
161 °C; 1H NMR δ 3.86 (s, 3H), 6.31 (dd, J ) 9.0, 2.2, 1H),
6.43 (d, J ) 2.2, 1H), 7.84 (d, J ) 9.0, 1H).
1-Nitr o-2-n a p h th yla m in e (12): mp 123-125 °C; lit.44 mp
2-Nitr o-N-(N,N-tetr a m eth ylen eth ioca r ba m oylth io)a n i-
lin e (15): mp 138-140 °C; 1H NMR (DMSO-d6) δ 1.89 (m,
2H), 2.07 (m, 2H), 3.70 (m, 4H), 7.01 (m, 1H), 7.43 (dd, J )
8.6, 1.3, 1H), 7.61 (m, 1H), 8.06 (dd, J ) 8.4, 1.5, 1H). Anal.
Calcd for C11H13N3O2S2: C, 46.63; H, 4.62; N, 14.83. Found:
C, 46.53; H, 4.48; N, 14.71.
1
123-124 °C; H NMR δ 7.23 (d, J ) 9.1, 1H), 7.35 (m, 1H),
7.60 (m, 1H), 7.79 (dd, J ) 7.9, 1.5, 1H), 7.87 (d, J ) 9.1, 1H),
8.58 (dm, J ) 8.7, 1H).
4-Meth oxy-1-n itr o-2-n a p h th yla m in e (12b): mp 176-177
°C; 1H NMR δ 4.05 (s, 3H), 6.64 (s, 1H), 7.35 (m, 1H), 7.62 (m,
1H), 8.11 (dd, J ) 8.2, 1.5, 1H), 8.81 (d, J ) 8.8, 1H). Anal.
Calcd for C11H10N2O3: C, 60.55; H, 4.62; N, 12.84. Found: C,
60.40; H, 4.76; N, 12.75.
3-Am in o-4-n itr oben zon itr ile (18b): mp 128-131 °C;45 1
H
NMR δ 6.99 (dd, J ) 8.8, 1.7, 1H), 7.51 (d, J ) 1.7, 1H), 8.21
(d, J ) 8.8, 1H). Anal. Calcd for C7H5N3O2: C, 51.54; H, 3.09;
N, 25.76. Found: C, 51.13; H, 3.16; N, 25.91.
5-Br om o-1-n itr o-2-n a p h th yla m in e (12c): 1H NMR (DM-
SO-d6, mixture with 13c) δ 7.31 (d, J ) 9.5, 1H), 7.46 (dd, J )
8.7, 7.6, 1H), 7.66 (dd, J ) 7.6, 1.2, 1H), 8.12 (dd, J ) 9.5, 0.7,
1H), 8.32 (dm, J ) 8.7, 1H). Isolated as N-acetyl derivative:
mp 191-194 °C; 1H NMR δ 2.22 (s, 3H), 7.62 (dd, J ) 8.7, 7.5,
1H), 7.83 (dm, J ) 8.7, 1H), 7.98 (dd, J ) 7.5, 1.0, 1H), 8.22
2-Nitr o-5-tr iflu or om eth yla n ilin e (18c): mp 98-101 °C;
1
lit.44 mp 103 °C; H NMR δ 6.95 (dd, J ) 8.9, 2.0, 1H), 7.47
(bs, 1H), 8.25 (d, J ) 8.9, 1H).
3-F lu or o-6-n itr oa n ilin e (18d ): mp 93-95 °C; lit.44 mp 97
1
°C; H NMR δ 6.49 (m, 1H), 6.80 (dd, J ) 11.1, 2.7, 1H), 8.15
(dd, J ) 9.5, 6.1, 1H).
3-Ch lor o-6-n itr oa n ilin e (18e): mp 128-129 °C; lit.44 mp
(44) Beilsteins Handbuch der Organischen Chemie: compound 10
Vol. 12, E III, 1513; 10c Vol. 12, E III, 2010; 11 Vol. 12, E III, 1580;
11b Vol. 14, E III, 1021; 11c Vol. 12, E III, 2011; 11d Vol. 12, E III,
1648; 11e Vol. 12, E III, 1665; 11f Vol. 12, E III, 1676; 11g Vol. 13, E
I, 136; 12 Vol. 12, E II, 731; 12f Vol. 22, E I, 639; 13 Vol. 12, E III,
2971; 13f Vol. 22, E II, 357; 18c Vol. 12, E III, 2010; 18d Vol. 12, E
III, 1646; 18e Vol. 12, E III, 1655; 18f Vol. 13, E III, 975; 18g Vol. 12,
H, 1166; 25h Vol. 12, E III, 1658; 25k Vol. 13, E II, 191; 26a Vol. 12,
E III, 1681; 26b Vol. 14, E III, 980; 26c Vol. 14, E I, 556; 26d Vol. 14,
E III, 980; 26f Vol. 12, E III, 1944; 26g Vol. 12, E III, 1647; 26h Vol.
12, E III, 1662; 26i Vol. 12, E III, 1675; 26j Vol. 12, H, 846; 26k Vol.
13, E III, 888; 27b Vol. 14, E III, 1161; 27c Vol. 14, E I, 583; 27e Vol.
14, E I, 390; 27f Vol. 12, E III, 2183; 27h Vol. 12, E III, 1649; 27k Vol.
13, E II, 286; 30 Vol. 7, H, 717; 35 Vol. 12, H, 1258; 35a Vol. 22, E IV,
4680; 37b Vol. 22/ 11, E V, 422; 45c Vol. 14, E III, 984.
1
128-129 °C; H NMR δ 6.70 (dd, J ) 9.2, 2.2, 1H), 7.15 (d,
2.2, 1H), 8.07 (d, J ) 9.2, 1H).
3-Meth oxy-6-n itr oa n ilin e (18f): mp 130-132 °C; lit.44 mp
1
129-130.5 °C; H NMR δ 3.84 (s, 3H), 6.29 (dd, J ) 9.5, 2.7,
1H), 6.51 (d, J ) 2.7, 1H), 8.00 (d, J ) 9.5, 1H).
3-ter t-Bu tyl-6-n itr oa n ilin e (18g): mp 90-91 °C; lit.44 mp
91-92 °C; 1H NMR δ 1.29 (s, 9H), 6.78 (dd, J ) 9.1, 2.1, 1H),
7.07 (d, J ) 2.1, 1H), 7.96 (d, J ) 9.1, 1H).
(45) Mu¨ller, E.; Hauel, N.; Noll, K.; Narr, B.; Heider, J .; Psiorz, M.;
Bomhard, A.; Meel, V. J .; Diederen, W. GP 3,522,230, 1987; Chem.
Abstr. 1987, 106, 156,466.

Nitroarylamines via VNS of Hydrogen
J . Org. Chem., Vol. 63, No. 15, 1998 4887
4-Nitr o-N-(N,N-tetr a m eth ylen eth ioca r ba m oylth io)a n i-
lin e (19): mp 181-183 °C; 1H NMR δ 1.91-2.24 (m, 4H), 3.72
(t, J ) 6.8, 2H), 3.81 (t, J ) 7.0, 2H), 7.18 (m, AA′ portion of
AA′XX′, 2H), 8.12 (m, XX′ portion of AA′XX′ system, 2H). Anal.
Calcd for C11H13N3O2S2: C, 46.63; H, 4.62; N, 14.83. Found:
C, 46.68; H, 4.55; N, 14.73.
2,4,6-Tr ich lor o-4′-cya n oben zen esu lfen a n ilid e (21): mp
195-198 °C; 1H NMR δ 7.33 (m, AA′ portion of AA′XX′ system,
2H), 7.59 (m, XX′ portion of AA′XX′ system, 2H), 7.60 (s, 2H).
Anal. Calcd for C13H7Cl3N2S: C, 47.37; H, 2.14; N, 8.50.
Found: C, 47.17; H, 1.95; N, 8.22.
Meth yl 4-a m in o-3-n itr oben zoa te (27c): mp 204-207 °C;
lit.44 mp 199.5-200.0 °C; 1H NMR δ 3.86 (s, 3H), 7.14 (d, J )
8.9, 1H), 7.93 (dd, J ) 8.9, 2.0, 1H), 8.71 (d, J ) 2.0, 1H).
4-Am in o-3-n itr oben zop h en on e (27e): mp 139-141 °C;
lit.44 mp 140.5 °C; 1H NMR δ 7.22 (d, J ) 8.9, 1H), 7.52-7.80
(m, 5H), 7.93 (dd, J ) 8.9, 2.1, 1H), 8.52 (d, J ) 2.1, 1H).
2-Nitr o-4-tr iflu or oa n ilin e (27f): mp 102-105 °C; lit.44 mp
1
109-110 °C; H NMR δ 7.28 (d, J ) 8.7, 1H), 7.67 (dd, J )
8.7, 2.1, 1H), 8.35 (bs, 1H).
4-Ch lor o-2-n itr oa n ilin e (27h ): mp 105-110 °C; lit.44 mp
1
116-117 °C; H NMR δ 7.14 (d, J ) 9.0, 1H), 7.42 (dd, J )
2,4,6-Tr ich lor op h en yl th iocya n a te (22) was obtained
from 2,4,6-trichloroaniline46 and proved to be identical with a
sample isolated from the reaction (Table 2, entry 2): mp 71-
9.0, 2.5, 1H), 8.03 (d, J ) 2.5, 1H).
4-Meth oxy-2-n itr oa n ilin e (27k ): mp 120-122 °C; lit.44
mp 123 °C; 1H NMR δ 3.79 (s, 3H), 7.05 and 7.14 (m, AB
portion of ABX system, J ) 9.2, 3.0, 0.4, 2H), 7.48 (m, X portion
of ABX system, J ) 3.0, 0.4, 1H).
1
75 °C; H NMR δ 7.84 (s, 2H). Anal. Calcd for C7H2Cl3NS:
C, 35.25; H, 0.85; N, 5.87. Found: C, 35.17; H, 0.79; N, 5.81.
2,4,6-Tr ich lor o-4′-n itr oben zen esu lfen a n ilid e (23): mp
150 °C; 1H NMR δ 7.35 (m, AA′ portion of AA′XX′ system, 2H),
7.60 (s, 2H), 8.12 (m, XX′ portion of AA′XX′ system, 2H). Anal.
Calcd for C12H7Cl3N2O2S: C, 41.23; H, 2.02; N, 8.01. Found:
C, 42.18; H, 1.72; N, 7.98.
3-Nitr o-N-(N,N-tetr am eth ylen eth iocar bam oylth io)ben z-
1
a m id e (28): mp 132-134 °C; H NMR δ 2.01 (quintet, J )
5.5, 2H), 2.20 (quintet, J ) 6.5, 2H), 3.70 (t, J ) 6.8, 2H), 3.84
(t, J ) 6.9, 2H), 7.88 (m, 1H), 8.45-8.52 (m, 2H), 8.89 (m, 1H).
Anal. Calcd for C12H13N3O3S2: C, 46.29; H, 4.21; N, 13.49.
Found: C, 46.05; H, 4.46; N, 13.25.
2-Am in o-3-n itr oben zon itr ile (25b): mp 129-130 °C;47 1
H
Na p h th o[1,2]fu r a za n (29): 77-78 °C; lit.49 mp 78-79 °C;
1H NMR δ 7.75 (d, J ) 9.4, 1H), 7.79-7.90 (m, 2H), 7.93 (d, J
) 9.4, 1H), 8.02-8.08 (m, 1H), 8.56 (m, 1H).
NMR δ 6.90 (dd, J ) 8.6, 7.5, 1H), 7.94 (dd, J ) 7.5, 1.6, 1H),
8.40 (dd, J ) 8.6, 1.6, 1H). Anal. Calcd for C7H5N3O2: C,
51.54; H, 3.09; N, 25.76. Found: C, 51.24; H, 2.80; N, 25.71.
2-Ch lor o-6-n itr oa n ilin e (25h ): mp 73 °C; lit.44 mp 72-
73 °C; 1H NMR δ 6.76 (dd, J ) 8.7, 7.7, 1H), 7.68 (dd, J ) 7.7,
1.5, 1H), 8.10 (dd, J ) 8.7, 1.5, 1H).
1-Nitr oso-2-n a p h th yla m in e (30): mp 147-149 °C; lit.44
1
mp 150-152 °C; H NMR (DMSO-d6) δ 7.05 (d, J ) 9.3, 1H),
7.47 (m, 1H), 7.66 (m, 1H), 7.81 (d, J ) 7.8, 1H), (d, J ) 9.3,
1H), 9.05 (d, J ) 8.3, 1H). NOE was observed between signals
δ 7.81 and 7.91.
2-Meth oxy-6-n itr oa n ilin e (25k ): mp 74-75.5 °C; lit.44 mp
76 °C; 1H NMR δ 3.95 (s, 3H), 6.64 (dd, J ) 8.9, 7.8, 1H), 7.08
(dd, J ) 7.8, 1.2, 1H), 7.65 (dd, J ) 8.9, 1.2, 1H).
5-Br om o-1-n itr oso-2-n a p h th yla m in e (31): mp 193 °C
(dec); 1H NMR (500 MHz, CD3CN) δ 7.10 (d, J ) 9.5, 1H), 7.55
(dd, J ) 8.4, 7.7, 1H), 7.78 (d, J ) 7.7, 1H), 8.21 (d, J ) 9.5,
1H), 9.25 (d, J ) 8.4, 1H); HRMS (EI, 70 eV) calcd for
2,4-Din itr oa n ilin e (26a ): mp 180 °C, lit.44 mp 181-182
°C; 1H NMR δ 7.25 (d, J ) 9.4, 1H), 8.21 (dd, J ) 9.4, 2.7,
1H), 8.94 (d, J ) 2.7, 1H).
2-Am in o-5-n itr oben zon itr ile (26b): mp 202-204 °C; lit.44
mp 210 °C; 1H NMR δ 7.04 (d, J ) 9.4, 1H), 8.19 (dd, J ) 9.4,
2.7, 1H), 8.38 (d, J ) 2.7, 1H).
C
10H779BrN2O 249.9742, found 249.9738.
6-Na p h th o[1,2]fu r a za n ca r boxa ld eh yd e eth ylen e a c-
1
eta l (32): mp 145-146 °C; H NMR δ 4.20 (m, 4H), 6.39 (s,
1H), 7.80 (d, J ) 9.9, 1H), 7.84 (m, 1H), 8.06 (d, J ) 7.7, 1H),
8.31 (d, J ) 9.9, 1H), 8.61 (dm, J ) 7.8, 1H). Anal. Calcd for
Meth yl 2-a m in o-5-n itr oben zoa te (26c): mp 169-170 °C;
lit.44 mp 168 °C; 1H NMR δ 3.93 (s, 3H), 6.96 (d, J ) 9.3, 1H),
8.11 (dd, J ) 9.3, 2.7, 1H), 8.71 (d, J ) 2.7, 1H).
C
13H10N2O3: C, 64.46; H, 4.16; N, 11.56. Found: C, 64.25; H,
t-Bu tyl 2-a m in o-5-n itr oben zoa te (26c′): mp 157-158 °C;
1H NMR δ 1.63 (s, 9H), 6.94 (d, J ) 9.3, 1H), 8.09 (dd, J ) 9.3,
2.8, 1H), 8.67 (d, J ) 2.8, 1H). Anal. Calcd for C11H14N2O4:
C, 55.46; H, 5.92; N, 11.76. Found: C, 55.23; H, 6.01; N, 11.63.
2-Am in o-5-n itr oben zoic a cid (26d ): mp 274-276 °C;
3.85; N, 11.44.
5-Nitr oso-6-a m in oqu in olin e (33): mp 176 °C (dec); 1H
NMR δ 7.38 (d, J ) 9.5, 1H), 7.69 (dd, J ) 8.4, 4.4, 1H), 8.02
(dd, J ) 9.5, 0.7, 1H), 8.81 (dd, J ) 4.4, 1.7, 1H), 9.53 (d, J )
8.4, 1H); HRMS (EI, 70 eV) calcd for C9H7N3O 173.0589, found
173.0582.
1
lit.44 mp 276 °C; H NMR δ 6.97 (d, J ) 9.3, 1H), 8.12 (dd, J
) 9.3, 2.7, 1H), 8.78 (d, J ) 2.7, 1H).
2-Nitr o-1-n a p h th yla m in e (35): mp 144-146 °C; lit.44 mp
1
2-Am in o-5-n itr oben zop h en on e (26e): mp 143-146 °C;
144 °C; H NMR δ 7.14 (dm, J ) 9.5, 1H), 7.62 (m, 1H), 7.72
1
lit.48 mp 152-154 °C; H NMR δ 7.07 (d, J ) 9.3, 1H), 7.54-
(m, 1H), 7.88 (dd, J ) 8.0, 1.6, 1H), 8.06 (d, J ) 9.5, 1H), 8.50
(dm, J ) 8.3, 1H).
7.75 (m, 5H), 8.16 (dd, J ) 9.3, 2.7, 1H), 8.39 (d, J ) 2.7, 1H).
4-Nitr o-2-tr iflu or om eth yla n ilin e (26f): mp 90-92 °C;
lit.44 mp 88 °C; 1H NMR δ 7.05 (d, J ) 9.2, 1H), 8.17 (dd, J )
9.2, 2.6, 1H), 8.30 (d, J ) 2.6, 1H).
6-Nitr o-5-a m in oqu in olin e (35a ): mp 281-285 °C; lit.44
mp 272-273 °C; 1H NMR (acetone-d6/DMSO-d6) δ 7.18 (dd, J
) 9.7, 0.7, 1H), 7.58 (dd, J ) 8.6, 4.3, 1H), 8.25 (d, J ) 9.7,
1H), 8.98 (dd, J ) 4.3, 1.6, 1H), 9.06 (dm, J ) 8.6, 1H).
2-Am in o-4-eth oxy-5-n itr op yr id in e (37a ): mp 218-220
°C; 1H NMR δ 1.42 (t, J ) 7.0, 3H), 4.18 (q, J ) 7.0, 2H), 6.23
(s, 1H), 8.64 (s, 1H). Anal. Calcd for C7H9N3O3: C, 45.90; H,
4.95; N, 22.94. Found: C, 46.02; H, 4.70; N, 22.79.
2-Am in o-6-m eth oxy-3-n itr op yr id in e (37b): mp 169-171
°C; lit.44 mp 171-172 °C; 1H NMR δ 3.91 (s, 3H), 6.16 (d, J )
9.1, 1H), 8.30 (d, J ) 9.1, 1H).
2-F lu or o-4-n itr oa n ilin e (26g): mp 125-128 °C; lit.44 mp
1
134 °C; H NMR δ 6.96 (m, 1H), 7.85-7.94 (m, 2H).
2-Ch lor o-4-n itr oa n ilin e (26h ): mp 99-101 °C; lit.44 mp
1
106-107 °C; H NMR δ 6.98 (d, J ) 9.0, 1H), 7.99 (dd, J )
9.0, 2.6, 1H), 8.15 (d, J ) 2.6, 1H).
2-Br om o-4-n itr oa n ilin e (26i): mp 104-105 °C; lit.44 mp
1
106-107 °C; H NMR δ 6.98 (d, J ) 9.1, 1H), 8.02 (dd, J )
9.1, 2.5, 1H), 8.30 (d, J ) 2.5, 1H).
2-Meth yl-4-n itr oa n ilin e (26j): mp 131-132 °C; lit.44 mp
130 °C; 1H NMR δ 2.23 (s, 3H), 6.76 (m, X portion of ABX
system, 1H), 7.87-7.92 (m, AB portion of ABX system, 2H).
2-Meth oxy-4-n itr oa n ilin e (26k ): mp 140-141 °C; lit.44
mp 139 °C; 1H NMR δ 3.97 (s, 3H), 6.77 (d, J ) 8.8, 1H), 7.64
(d, J ) 2.4, 1H), 7.76 (dd, J ) 8.8, 2.4, 1H).
2-Am in o-3-n itr oth iop h en e (39a ): mp 168-171 °C; lit.50
mp 150-153 °C; 1H NMR δ 6.42 (d, J ) 6.2, 1H), 7.13 (d, J )
6.2, 1H).
1-Met h yl-4-n it r o-5-a m in oim id a zole (39b ): mp 299 °C
(dec), lit.51 mp 303 °C; 1H NMR (DMSO-d6) δ 3.43 (s, 3H), 7.25
(s, 1H).
4-Am in o-3-n itr oben zon itr ile (27b): mp 161-162 °C; lit.44
mp 160 °C; 1H NMR δ 7.23 (d, J ) 8.9, 1H), 7.68 (dd, J ) 8.9,
2.0, 1H), 8.47 (d, J ) 2.0, 1H).
1,2-Dim eth yl-4-a m in o-5-n itr oin d ole (41): mp 166-168
°C; 1H NMR δ 2.41 (s, 3H), 3.71 (s, 3H), 6.68 (m, 1H), 6.75 (d,
J
) 9.4, 1H), 7.82 (d, J ) 9.4, 1H). Anal. Calcd for
(46) Pilgram, K.; Korte, F. Tetrahedron 1965, 21, 1999.
(47) Franc, J . CSP 200,689, 1983; Chem. Abstr. 1983, 99, 151,473.
(48) Konwar, D.; Boruah, R. C.; Sandhu, J . S.; Baruah, J . N. Synth.
Commun. 1984, 14, 1053.
(49) Stepanov, B. I.; Sakharova, N. A. Zh. Org. Khim. 1975, 11, 138.
(50) Nippon Kayaku Co. Ltd J P 81,100,780, 1981; Chem. Abstr.
1982, 96, 19,954.
(51) Balaban, I. E. J . Chem. Soc. 1930, 268.

4888 J . Org. Chem., Vol. 63, No. 15, 1998
Ma¸kosza and Białecki
C10H11N3O2: C, 58.53; H, 5.40; N, 20.48. Found: C, 58.68; H,
5.16; N, 19.79.
1H), 6.99 (m, AA′ portion of AA′BB′, 2H), 7.27 (m, BB′ portion
of AA′BB′, 2H), 7.71 (d, J ) 2.4, 1H), 7.79 (dd, J ) 9.0, 2.4,
1H). Anal. Calcd for C14H14N2O4: C, 61.31; H, 5.14; N, 10.21.
Found: C, 61.17; H, 5.02; N, 10.32.
N-Cycloh exyl-1-n itr o-2-n a p h th yla m in e (45h ): mp 104-
106 °C; 1H NMR δ 1.30-1.87 (m, 10H), 3.86 (m, 1H), 7.35 (m,
1H), 7.38 (d, J ) 9.4, 1H), 7.60 (m, 1H), 7.80 (dd, J ) 7.9, 1.5,
1H), 7.96 (d, J ) 9.4, 1H), 8.60 (dm, J ) 8.8, 1 H); NOE was
observed between signals δ 7.80 and 7.96 (500 MHz). Anal.
Calcd for C16H18N2O2: C, 71.09; H, 6.71; N, 10.36. Found: C,
71.06; H, 6.83; N, 10.36.
4-Nitr o-N-p h en yl-3-tr iflu or om eth yla n ilin e (45a ): mp
1
154-155 °C; lit.52 mp 149-150 °C; H NMR δ 7.15-7.23 (m,
1H), 7.31-7.49 (m, 6H), 8.10 (d, J ) 9.0, 1H).
3-Ch lor o-N-cycloh exyl-4-n itr oa n ilin e (45b): mp 92-93
1
°C; H NMR δ 1.16-1.81 (m, 10H), 3.37-3.55 (m, 1H), 6.66
(dd, J ) 9.2, 2.5, 1H), 6.74 (d, J ) 2.5, 1H), 7.95 (d, J ) 9.2,
1H). Anal. Calcd for C12H15ClN2O2: C, 56.59; H, 5.94; N,
11.00. Found: C, 56.87; H, 5.98; N, 10.76.
5-Nitr o-2-(p h en yla m in o)ben zon itr ile (45c): mp 165-
1
N-Cycloh exyl-1-n itr o-4-n a p h th yla m in e (45i): mp 148-
167 °C; lit.44 mp 171 °C; H NMR δ 7.17-7.53 (m, 5H), 7.19
1
150 °C; H NMR δ 1.22-1.88 (m, 10H), 3.74 (m, 1H), 6.75 (d,
(d, J ) 9.5, 1H), 8.25 (dd, J ) 9.5, 2.7, 1H), 8.50 (d, J ) 2.7,
1H).
J ) 9.0, 1H), 7.53 (m, 1H), 7.73 (m, 1H), 8.31 (dm, J ) 8.6,
1H), 8.45 (d, J ) 9.0, 1H), 8.97 (dd, J ) 8.8, 1.3, 1H). Anal.
Calcd for C16H18N2O2: C, 71.09; H, 6.71; N, 10.36. Found: C,
70.90; H, 6.89; N, 10.31.
2-Ch lor o-4-n itr o-N-p h en yla n ilin e (45d ): mp 111-112
1
°C; lit.53 mp 112-113 °C; H NMR δ 7.16-7.29 (m, 1H), 7.18
(d, J ) 9.2, 1H), 7.34-7.50 (m, 4H), 8.04 (dd, J ) 9.2, 2.6,
1-Nitr o-N-p h en yl-4-n a p h th yla m in e (45j): mp 157-158
°C; 1H NMR (500 MHz) δ 7.16 (d, J ) 8.9, 1H), 7.17-7.23 (m,
1H), 7.41-7.48 (m, 4H), 7.66 (m, 1H), 7.81 (m, 1H), 8.36 (d, J
) 8.9, 1H), 8.48 (d, J ) 8.6, 1H), 8.87 (dm, J ) 8.8, 1H). Anal.
Calcd for C16H12N2O2: C, 72.72; H, 4.58; N, 10.60. Found: C,
72.51; H, 4.37; N, 10.64.
1H), 8.25 (d, J ) 2.6, 1H).
2-Ch lor o-N-(4-m eth oxyph en yl)-4-n itr oan ilin e (45e): mp
112-113 °C; lit.53 mp 99-100 °C; 1H NMR δ 3.84 (s, 3H), 6.92
(m, 1H), 7.03 (m, AA′ portion of AA′BB′, 2H), 7.29 (m, BB′
portion of AA′BB′, 2H), 8.01 (dd, J ) 9.3, 2.6, 1H), 8.23 (d, J
) 2.6, 1H).
2-Nitr o-3-(p h en yla m in o)th iop h en e (47a ): mp 103-105
2-Br om o-N-cycloh exyl-4-n itr oa n ilin e (45f): mp 90-91
1
°C; lit.54 mp 104 °C; H NMR δ 7.05 (d, J ) 6.1, 1H), 7.23-
1
°C; H NMR δ 1.22-1.83 (m, 10H), 3.60 (m, 1H), 6.89 (d, J )
7.31 (m, 1H), 7.41-7.49 (m, 4H), 7.81 (d, J ) 6.1, 1H).
2-(P h en yla m in o)-5-n itr oth iop h en e (47b): mp 186 °C;
lit.55 mp 193 °C; 1H NMR δ 6.52 (d, J ) 4.8, 1H), 7.15 (m, 1H),
7.34-7.50 (m, 4H), 7.85 (d, J ) 4.8, 1H).
9.3, 1H), 8.08 (dd, J ) 9.3, 2.6, 1H), 8.30 (d, J ) 2.6, 1H). Anal.
Calcd for C12H15BrN2O2: C, 48.18; H, 5.05; N, 9.36. Found:
C, 48.08; H, 5.07; N, 9.63.
2-Meth oxy-N-(4-m eth oxyp h en yl)-4-n itr oa n ilin e (45g):
dark orange oil; 1H NMR δ 3.82 (s, 3H), 4.02 (s, 3H), 6.91 (m,
J O970582B
(52) Humm, A. W.; Schneider, M. R. Arch. Pharm. (Weinheim) 1990,
323 83.
(54) Bacon, R. G. R.; Hamilton, S. D. J . Chem. Soc., Perkin Trans.
1 1974, 1970.
(53) Day, M.; Peters, A. T., J r. J . Soc. Dyers Colourists 1967, 83,
137.
(55) Dell’Erba, C.; Spinelli, D. Boll. Sci. Fac. Chim. Ind. Bologna
1968, 26, 97; Chem. Abstr. 1968, 69, 106,381.