New synthetic equivalent of nitromalonaldehyde treatable in organic media

Article abstract of DOI:10.1021/jo0488513

β-Nitroenamines having a formyl group at the β-position behave as the synthetic equivalent of unstable nitromalonaldehyde, which is a useful synthon for syntheses of versatile nitro compounds. High solubility of the nitroenamines into general organic solv

Full text of DOI:10.1021/jo0488513

New Synthetic Equivalent of Nitromalonaldehyde Treatable in
Organic Media
Nagatoshi Nishiwaki,* Takuma Ogihara, Toshiko Takami, Mina Tamura, and
Masahiro Ariga*
Department of Chemistry, Osaka Kyoiku University, Asahigaoka 4-698-1,
Kashiwara, Osaka 582-8582, Japan
ariga@cc.osaka-kyoiku.ac.jp
Received July 7, 2004
â-Nitroenamines having a formyl group at the â-position behave as the synthetic equivalent of
unstable nitromalonaldehyde, which is a useful synthon for syntheses of versatile nitro compounds.
High solubility of the nitroenamines into general organic solvents enables us to conduct reactions
in the organic media accompanied by easy experimental manipulations and considerable safety.
When nitroenamines are treated with 1,2-bifunctional nucleophiles such as hydrazines, hydroxyl-
amine and glycine ester, nitrated pyrazoles, isoxazole and pyrrole-2-carboxylate were readily
prepared. This methodology was also applicable to guanidines and 1,2-diamines, leading to
pyrimidines and 1,4-diazepines, respectively.
Introduction
Nitro compounds constitute an important class among
organic compounds and are highly useful in synthetic
1
-5
chemistry.
Several preparative methods for nitro
compounds have been developed. Nitration is the most
powerful method for direct introduction of a nitro group
into carbon skeletons although it often suffers from
restrictions such as severe conditions, limited scope of
FIGURE 1. Synthetic equivalents of nitromalonaldehyde
NMA-H.
1,2,6
substrates, and regioselectivity.
Oxidation of amines
a building block having a nitro group is built in the
framework upon treatment with bifunctional nucleo-
philes. Nitromalonaldehyde (NMA-H) often appears as
the synthon in retrosyntheses for various kinds of nitro
compounds, but it actually cannot be employed because
of instability. Its sodium salt (NMA-Na) has been used
as the synthetic equivalent of NMA-H from previous
1
1,7
or oximes, cycloaddition of nitroalkenes, and Michael
addition with nitroalkanes as nucleophiles1 are also
effective procedures; however, starting materials for
these reactions are not always easily available. From this
viewpoint, it is highly demanded to develop a compensa-
tory method for the preparation of nitro compounds. As
another methodology for construction of nitro compounds,
,8
9
times (Figure 1). The salt NMA-Na is prepared from
furfural via mucobromic acid with somewhat troublesome
manipulations,10 and the insolubility of NMA-Na into
general organic solvents obliges us to conduct reactions
in aqueous medium or in the highly polar solvent.
Furthermore, crude NMA-Na is impact sensitive and
thermally unstable, and it should be handled as a
potentially explosive material.9 Despite some serious
problems mentioned here, NMA-Na is widely used even
now for the synthesis of nitro compounds due to the
absence of any other efficient reagents. Hence, it is highly
desired to develop a convenient and safe synthetic
equivalent of NMA-H treatable in organic media in place
of NMA-Na.
(
1) Ono, N. The Nitro Group in Organic Synthesis; Wiley-VCH: New
York, 2001.
(
2) The Chemistry of the Nitro and Nitroso Groups (Patai); Feuer,
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(
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4) (a) R a´ dl, S. Advances in Heterocyclic Chemistry; Academic
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(
(
4
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Chem. Lett. 2000, 48. (e) Olah, G. A.; Malhotra, R.; Narang, S. C.
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(
7) (a) Denmark, S. E.; Gomez, L. J. Org. Chem. 2003, 68, 8015. (b)
In our course of study on ring-opening reactions of
electron-deficient heterocyclic compounds, functionalized
Zhang, M.-X.; Eaton, P. E.; Steele, I.; Gilardi, R. Synthesis 2002, 2013.
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c) McAlonan, H.; Murphy, J. P.; Nieuwenhuyzen, M.; Reynolds, K.;
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(
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10.1021/jo0488513 CCC: $27.50 © 2004 American Chemical Society
8382
J. Org. Chem. 2004, 69, 8382-8386
Published on Web 10/30/2004

Synthetic Equivalent of Nitromalonaldehyde
SCHEME 1. Preparative Routes for Nitroenamines 4 from Nitropyrimidinone 1
nitroenamines were found to be easily prepared.11,12 Since
TABLE 1. Preparation of Nitropyrazoles 6
the C4-C5-C6 moiety of 1-methyl-5-nitropyrimidin-
2
(1H)-one (1) could be regarded as the masked NMA-H,
its aminolyzed products were considered to behave as the
synthetic equivalent of NMA-H. When pyrimidinone 1
was heated with 2 equiv of primary amines in methanol,
the ring-opening reaction readily proceeded to give oily
1
Run
1
R
6
temp/°C
time/h
yield/%
product. In the H NMR of the product, two substituents
(
R) on the nitrogens were equivalently observed, which
Me
H
t-Bu
t-Bu
a
b
c
rt
3
3
24
3
24
3
96
87
29
59
90
35
47
0
a
2
rt
indicated that the product was assigned as symmetrical
diimine 2 or as a tautomeric mixture of azadienamines
3
a
3
rt
a
4
80
rt
under rapid equilibrium.12 The X-ray crystallography
5
6
CH2COOEt
Ph
p-MeC6H4
p-NO2C6H4
d
e
f
13a
a
and calculation of their heat of formation showed high
possibility presenting in the latter structure 3. When
Schiff base 2 (or 3) was charged on silica gel in a column
and stood at room temperature for 1 day, the hydrolysis
of an imino group proceeded to afford formylated nitro-
enamines 4 in good yields (Scheme 1). This preparative
method is advantageous from the viewpoint of easy
modification of the substituent (R) on the amino group
in 4, namely the use of different amines in the initial
aminolysis leads to nitroenamines having a modified
amino group.
80
80
80
7
3
3
a
8
g
a
Equimolar amount of triethylamine was added.
12
1
temperature for 3 h. In the H NMR of the residue after
evaporation, signals for only 1-methyl-4-nitropyrazole
16
6
a
were observed, and further purification of 6a was
readily performed with column chromatography on silica
gel. Nitroenamine 4a reacted with other hydrazines 5b-f
to give corresponding pyrazoles 6b-f 16 (Table 1). The use
of nitroenamine 4b instead of 4a did not cause a notable
change in the yield of 6. When reagents were com-
mercially available as hydrazinium hydrochlorides, a
equimolar amount of triethylamine was added to liberate
hydrazine. In the case of sterically hindered hydrazine
â-Nitroenamines 4 possess two electrophilic sites, the
R-position and the formyl group, and this structural
feature is considered to behave as the synthetic equiva-
lent of NMA-H with easy manipulations and safety
(
Figure 1). In addition, high solubility into organic
solvents will realize the use of 4 in organic media such
as hexane, benzene, toluene, dichloromethane, chloro-
form, alcohols, and so on. In the present paper, we would
like to show the synthetic utility of nitroenamines 4
affording nitrated azaheterocyclic compounds by conden-
sation with bidentate nucleophiles.
5
c, the yield of 6c was considerably lowered under
ambient conditions, and it could be improved at elevated
temperature. Ethyl hydrazinoacetate 5d afforded difunc-
tionalized pyrazole 6d in good yield at room temperature.
On the other hand, aromatic hydrazines 5e and 5f were
less reactive even at 80 °C leading to pyrazoles 6e and
6
f in moderate yields, which was due to the low nucleo-
Results and Discussion
philicity of the nitrogen adjacent to the aromatic ring.
Since hydrazines having a bulky alkyl or an aryl group
are hardly soluble into water, it is difficult to conduct
A. Condensation with 1,2-Dinucleophilic Re-
agents. The 4-nitropyrazole skeleton is focused on as the
first target system, which is often found in the biologically
active compounds or in their precursors.1
4-16
To a solution
(
14) (a) Yuan, R.; Kender, W. J.; Burns, J. K. J. Am. Soc. Horticul.
of nitroenamine 4a in methanol was added methyl-
hydrazine 5a, and the mixture was stirred at room
Sci. 2003, 128, 302. (b) Tercel, M.; Lee, A. E.; Hogg, A.; Anderson, R.
F.; Lee, H. H.; Siim, B. G.; Denny, W. A.; Wilsson, W. R. J. Med. Chem.
2
001, 44, 3511. (c) Dahmen, P.; Dollinger, M.; Schallner, O. Ger. Offen.,
DE4435476 (Chem. Abstr. 1996, 125, 28286).
(11) (a) Nishiwaki, N.; Okajima, Y.; Tamura, M.; Asaka, N.; Hori,
(15) Boyer, J. H. Nitroazoles; Wiley-VCH: New York, 1986.
(16) (a) 6a: Dumanovic, D.; Kosanovic, D.; Zuman, P. Heterocycles
1994, 37, 2009. (b) 6b: Vokin, A. I.; Shulunova, A. M.; Lopyrev, V. A.;
Komarova, T. N.; Turchninov, V. K. Russ. J. Org. Chem. 1998, 34, 1670
(translated from Zh. Org. Khim. 1998, 34, 1741). (c) 6d: Kanishchev,
M. I.; Kral, V.; Arnold, Z.; Semenov, V. V.; Shevelev, S. A.; Fainzil’berg,
A. A. Bull. Acad. Sci. USSR Div. Chem. Sci. 1986, 35, 2191 (translated
from Izv. Akad. Nauk SSSR Ser. Khim. 1986, 10, 2392). (d) 6e: Holzer,
W. Tetrahedron 1991, 47, 1393. (e) 6f: Finar, I. L.; Hurlock, R. J. J.
Chem. Soc. 1957, 3024.
K.; Tohda, Y.; Ariga, M. Heterocycles 2003, 60, 303. (b) Nishiwaki, N.;
Nakanishi, M.; Hida, T.; Miwa, Y.; Tamura, M.; Hori, K.; Tohda, Y.;
Ariga, M. J. Org. Chem. 2001, 66, 7535. (c) Nishiwaki, N.; Mizukawa,
Y.; Terai, R.; Tohda, Y.; Ariga, M. Arkivoc 2000, 1, 103.
(
12) Nishiwaki, N.; Tohda, Y.; Ariga, M. Bull. Chem. Soc. Jpn. 1996,
6
9, 1997.
(13) (a) Shimokawa, C.; Yokota, S.; Tachi, Y.; Nishiwaki, N.; Ariga,
M.; Itoh, S. Inorg. Chem. 2003, 42, 8395. (b) Yokota, S.; Tachi, Y.;
Nishiwaki, N.; Ariga, M.; Itoh, S. Inorg. Chem. 2001, 40, 5316.
J. Org. Chem, Vol. 69, No. 24, 2004 8383

Nishiwaki et al.
SCHEME 2. Reactions of Nitroenamines 4 with
Other 1,2-Dinucleophilic Reagents
SCHEME 3. Synthesis of Nitropyrimidine
Derivatives 12
heated with potassium tert-butoxide at 80 °C for 1 day,
only a complex mixture was obtained, and we obtained
no evidence for formation of pyrimidine derivative 12a.
2
1
The desired condensation proceeded to give 12a in a
quantitative yield in the reaction with triethylamine
instead of tert-butoxide (Scheme 3). N-Ethylguanidine
reactions with NMA-Na in the aqueous medium. Hence,
the high solubility of 4 into organic solvents enables
effective reactions in such cases.
Hydroxylamine hydrochloride 7 was employed as an-
other 1,2-dinucleophilic reagent (Scheme 2). The conden-
1
1b similarly reacted under the same conditions afford-
ing pyrimidine 12b. It was determined that the ethyl
group was attached to the ring nitrogen since two
different aromatic protons were observed in the H NMR.
1
sation of nitroenamine 4a with 7 occurred at room
temperature, giving nitroisoxazole 815 in a moderate
Nitroenamine 4 was also proved to react with 1,3-
dinucleophilic reagents easily, which resulted in the
construction of a six-membered ring.
yield; however, the reaction at higher temperature af-
forded only a complex mixture. Isolated nitroisoxazole 8
was transformed into unidentified products upon treat-
ment with hydroxylamine hydrochloride at room tem-
perature, thus the yield of 8 was lowered due to com-
petitive decomposition of 8 under the same conditions.
The synthetic utility of nitroenamine 4 can be shown
since nitroisoxazole 8 has not been prepared from NMA-
C. Condensation with 1,4-Dinucleophilic Re-
agents. The diazepine skeleton is also important for drug
design, and numerous diazepines have been prepared up
until now.22 However, 6-nitro[1,4]diazepines are rarely
seen in the literature except for a few papers dealing with
2
3
5
,7-diphenyl and 5,7-dimethyl derivatives and the 2,2-
24
9
,15
dimethyl derivative. From this viewpoint, we studied
the reaction of nitroenamine 4b with 1,2-diamines lead-
ing to 2,3-disubstituted 6-nitrodiazepines 14.
Na.
Glycine ethyl ester hydrochloride 9 was usable as the
nucleophile. Upon treatment of nitroenamine 4b with 9
in the presence of triethylamine at 80 °C for 3 h, ethyl
When 1,2-diaminoethane 13a was added to a methanol
solution of nitroenamine 4b, white precipitates were
immediately generated. After the mixture was stirred at
room temperature for 3 h, white precipitates were filtered
off (product 15a, yield 31%, based on 4b), and then the
filtrate was concentrated to afford white solid (diazepine
14a, yield 69%). Both products gave the same empirical
formulas with elemental analyses. While the low solubil-
ity of 15a into organic solvents prevented the recrystal-
lization and the structural determination, it was consid-
ered to be a mixture of oligomers in which the dimer (n
-nitropyrrole-2-carboxylate 1017 was isolated in 26%
4
yield, and the yield of 10 was improved up to 59% when
the reaction was conducted at room temperature for 7
days (Scheme 2). 4-Nitropyrrole-2-carboxylic acid deriva-
tives and their reduced form, 4-amino derivatives, are
useful building blocks for oligopyrrole peptides,18 which
bind in the minor groove of double-helical DNA. Recently
it was energetically studied on versatile ligands for
sequence-specific recognition in the DNA.19 The presence
of the carbonyl group at the 2-position is necessary for
causing nitration at the 4-position, but introduction of
the carbonyl group into the pyrrole ring often accompa-
nies multistep reactions and troublesome manipula-
)
1) was probably the major product. Quantitative
synthesis of diazepine 14a was realized by slowly adding
a solution of diamine to a solution of nitroenamine 4b to
avoid oligomerization (Table 2).
2
0
tions. Although another approach to 10 with NMA-Na
1
7
The present reaction was applicable to alkyl-substi-
tuted diamines 13b,c to give corresponding diazepines
is also known, this method suffers from restrictions
mentioned at the beginning of this paper. Hence, our
preparative method for pyrrole 10 is concluded to be
superior to other methods.
14b,c in good yields. Both isomeric 1,2-diaminocyclohex-
anes 13d,e effectively furnished bicyclic diazepines 14d,e
fused in the cis and trans mode, respectively. In the case
of 1,2-diaminobenzene 13f, different reactivity from other
B. Condensation with 1,3-Dinucleophilic Re-
agents. 2-Amino-5-nitropyrimidine was focused on as the
target skeleton having a six-membered ring. When ni-
troenamine 4b and guanidine hydrochloride 11a were
1
,2-diamines was revealed. In the mass spectrum of red
solid precipitated during the reaction, a parent peak for
dimeric structure 15f was observed; however, the peak
for benzodiazepine 14f was not detected. Although larger
(
(
(
17) Hale, W. J.; Hoyt, W. V. J. Am. Chem. Soc. 1915, 37, 2538.
18) Satz, A. L.; Bruice, T. C. Acc. Chem. Res. 2002, 35, 86.
19) (a) Renneberg, D.; Dervan, P. B. J. Am. Chem. Soc. 2003, 125,
(21) Roblin, R. O., Jr.; Winnek, P. S.; English, J. P. J. Am. Chem.
Soc. 1942, 64, 567.
5
(
707. (b) Yeung, B. K. S.; Boger, D. L. J. Org. Chem. 2003, 68, 5249.
c) Kumar, R.; Lown, J. W. Org. Biomol. Chem. 2003, 1, 3327. (d)
(22) Sharp, J. T. Comprehensive Heterocyclic Chemistry; Lwowski,
W., Ed.; Pergamon Press: Oxford, UK, 1984; Vol. 7, p 593.
(23) Lloyd, D.; McNab, H. Advances in Heterocyclic Chemistry;
Academic Press: London, UK, 1993; Vol. 56, p 1.
(24) Lloyd, D.; Mackie, R. K.; McNab, H.; Marshall, D. R. J. Chem.
Soc., Perkin Trans. 2 1973, 1729.
Oyoshi, T.; Kawakami, W.; Narita, A.; Bando, T.; Sugiyama, H. J. Am.
Chem. Soc. 2003, 125, 4752.
(
20) (a) Anderson, H. J. Can. J. Chem. 1959, 37, 2053. (b) Treibs,
A.; Kolm, H. G. Justus Liebigs Ann. Chem. 1958, 577, 176. (c) Fischer,
H.; Zerweck, W.; Kenntnis, Z. Chem. Ber. 1922, 55, 1954.
8384 J. Org. Chem., Vol. 69, No. 24, 2004

Synthetic Equivalent of Nitromalonaldehyde
TABLE 2. Preparation of Nitrodiazepines 14
with nitric acid in sulfuric acid. To a solution of pyrimidinone
(310 mg, 2 mmol) in methanol (40 mL) was added propyl-
1
amine (410 µL, 5 mmol), and the mixture was heated under
reflux for 3 h. After evaporation, the residue was extracted
with hexane (3 × 30 mL), and removal of hexane afforded
NMR pure diimine 2a (or azadienamine 3a) (390 mg, 1.96
mmol, 98%) as pale yellow oil. A solution of 2a (or 3a) (200
mg, 1 mmol) in chloroform (5 mL) was charged on silica gel
(
20 g) in a column and stood at room temperature for 1 day,
run
R1
R2
R3
14
yield/%
and then it was eluted with chloroform. The solvent was
removed under reduced pressure to give nitroenamine 4a (150
1
2
3
4
5
6
H
Et
H
H
H
H
H
H
H
H
a
b
c
d
e
f
quant.
80
1
2
mg, 93%). Nitroenamine 4b was similarly prepared by use
H
of tert-butylamine instead of propylamine.
Me
69
1
-tert-Butyl-4-nitropyrazole (6c). To a solution of nitro-
-(CH2)4- (cis)
-(CH2)4- (trans)
o-phenylene group
79
enamine 4a (244 mg, 1.54 mmol) in methanol (10 mL) were
added tert-butylhydrazine hydrochloride (212 mg, 1.70 mmol)
and triethylamine (0.23 mL, 1.70 mmol). The resultant solu-
tion was heated under reflux for 3 h, and concentrated under
reduced pressure. The residue was treated with column
chromatography on silica gel to give 6c (eluted with benzene/
chloroform ) 1/1, 153 mg, 0.90 mmol, 59%) as yellow needles.
86
0
oligomer might be formed as a byproduct, the major
content was considered to be dimer 15f (n ) 1), and we
have obtained no evidence for the presence of diazepine
-
1
1
Mp 76-77 °C. IR (KBr/cm ) 1502, 1311; H NMR (400 MHz,
25
1
4f in the mixture. In this case, dilution of the reaction
1
3
CDCl
MHz, CDCl
Anal. Calcd for C
3
) δ 1.62 (s, 9H), 8.09 (s, 1H), 8.25 (s, 1H); C NMR (100
mixture was not effective and 15f was also afforded. The
lack of flexibility of diaminobenzene 13f was considered
to be a reason for this different reactivity. In consider-
ation of the recent spotlight on the â-diketiminate
3
) δ 29.3 (q), 60.7 (s), 125.5 (d), 134.3 (s), 135.3 (s).
7
11 3 2
H N O : C, 49.69; H, 6.55; N, 24.83.
Found: C, 49.80; H, 6.73; N, 24.58. When other hydrazines
were employed, experiments were carried out in a similar way.
1
3
Pyrazoles 6a-f except for 6c could be found in the literature.16
ligand, oligomers 15 might also be useful as multiden-
tate ligands having nitro groups.
1
5
4
-Nitroisoxazole (8). To a solution of nitroenamine 4a
(296 mg, 1.87 mmol) in methanol (10 mL) was added hydroxyl-
amine hydrochloride 7 (143 mg, 2.06 mmol), and the resultant
solution was stirred at room temperature for 1 day. After
concentration, the residue was extracted with diethyl ether
(
3 × 20 mL), and removal of the solvent afforded yellow oil.
Upon treatment with column chromatography on silica gel,
isoxazole 8 (eluted with benzene, 69 mg, 0.61 mmol, 33%) was
isolated as yellow needles.
17
Ethyl 4-Nitropyrrole-2-carboxylate (10). To a solution
of nitroenamine 4b (346 mg, 2.0 mmol) in ethanol (30 mL) were
added glycine ethyl ester hydrochloride 9 (562 mg, 4.0 mmol)
and triethylamine (0.84 mL, 6.0 mmol), and the mixture was
stirred at room temperature for 7 days. After removal of
ethanol, chloroform (30 mL) was added, and precipitated tert-
butylammonium chloride was filtered off. The filtrate was
concentrated, and the residue was treated with column chro-
matography on silica gel to afford pyrrole 10 (eluted with
chloroform, 218 mg, 1.19 mmol, 59%) as a yellow powder.
3-Ethyl-2-imino-5-nitropyrimidine (12b). To a solution
of nitroenamine 4b (172 mg, 1.0 mmol) in ethanol (30 mL) were
added N-ethylguanidine hydrochloride 11b (247 mg, 2.0 mmol)
and triethylamine (0.28 mL, 2.0 mmol), and the mixture was
heated at 80 °C for 1 day. After removal of ethanol, the residue
was extracted with chloroform (3 × 30 mL). The organic layer
was dried over magnesium sulfate and concentrated to give
almost pure pyrimidine 12b (336 mg, 2.0 mmol, quant.).
Further purification was performed by recrystallization from
FIGURE 2. Oligomeric structures derived from 4b and 13.
Summary
Nitroenamines 4 are revealed to behave as the syn-
thetic equivalent of NMA-H constructing five-, six-, and
seven-membered rings upon treatment with bifunctional
nucleophiles, and leading to nitrated azaheterocycles.
While the conventional synthetic equivalent NMA-Na has
serious problems for employment in organic syntheses,
the present nitroenamines 4 solve these problems, espe-
cially safety issues. High solubility of 4 into general
organic solvents simplifies experimental manipulations,
and enables the use of bifunctional nucleophiles that are
not treatable in organic media. Hence, synthesis of
hitherto unknown nitro compounds becomes possible by
use of nitroenamine 4. The synthetic utility of nitro-
enamine 4 is concluded to be higher than that of NMA-
Na from the viewpoint of both treatability and safety.
benzene giving 12b as colorless plates. Mp 140-146 °C dec.
1
3
H NMR (400 MHz, CDCl ) δ 1.30 (dd, J ) 7.3, 7.3 Hz, 3H),
3
.58 (q, J ) 7.3 Hz, 1H), 3.59 (q, J ) 7.3 Hz, 1H), 6.0-6.2 (br,
13
1
H), 9.03 (d, J ) 3.2 Hz, 1H), 9.12 (d, J ) 3.2 Hz, 1H);
C
NMR (100 MHz, CDCl
d), 154.4 (d), 162.5 (s); MS (FAB) 169 (M + 1, 100%). Anal.
Calcd for C : C, 42.86; H, 4.80; N, 33.32. Found: C,
3.23; H, 4.92; N, 33.52.
3
) δ 14.1 (q), 36.0 (t), 133.4 (s), 153.9
+
(
6
8 4 2
H N O
4
Experimental Section
The Typical Procedure for Synthesis of Diazepines 14.
Preparation of Nitroenamine 4a.12 Nitropyrimidinone 1
To a solution of nitroenamine 4b (258 mg, 1.50 mmol) in
methanol (30 mL) was added a solution of 1,2-diaminoethane
was prepared in 70% overall yield by the condensation of
1
3a (0.10 mL, 1.50 mmol) in methanol (10 mL). The resultant
commercially available 1,1,3,3-tetramethoxypropane and N-
2
6
solution was stirred at room temperature for 2 h and concen-
trated under reduced pressure. The residue was washed with
methylurea in 12 M hydrochloric acid followed by nitration
(
25) (a) Acheson, R. M. J. Chem. Soc. 1956, 4731. (b) King, F. E.;
Spensley, P. C. J. Chem. Soc. 1952, 2144.
(26) Fox, J. J.; Praag, D. V. J. Am. Chem. Soc. 1960, 82, 486.
J. Org. Chem, Vol. 69, No. 24, 2004 8385

Nishiwaki et al.
1H), 8.5-9.3 (br, 1H); 13C NMR (100 MHz, acetone-d
a small amount of benzene to afford diazepine 14a (211 mg,
6
) δ 20.0
(q), 57.1 (t), 57.4 (d), 123.7 (s), 149.7 (d), 152.6 (d); MS (FAB)
1.49 mmol, quant.) as a pale yellow powder.
+
2
,3-Dihydro-6-nitro-1H-1,4-diazepine (14a). Mp 194-
6 9 3 2
156 (M + 1, 100%). Anal. Calcd for C H N O : C, 46.45; H,
-
1
1
1
95 °C dec. IR (KBr/cm ) 1571, 1344; H NMR (400 MHz,
5.85; N, 27.08. Found: C, 46.29; H, 5.90; N, 26.75.
1
3
DMSO-d
NMR (100 MHz, DMSO-d
FAB) 142 (M + 1, 100%). Anal. Calcd for C
6
) δ 3.65 (s, 4H), 8.50 (s, 2H), 9.3-9.6 (br, 1H);
) δ 50.8 (t), 122.0 (s), 151.2 (d); MS
: C, 42.55;
C
cis-5a,6,7,8,9,9a-Hexahydro-3-nitro-1H-benzo[b][1,4]-
diazepine (14d). White powder; mp 260-261 °C. IR (KBr/
6
+
(
H N O
5 7 3 2
-1
1
cm ) 1573, 1336; H NMR (400 MHz, DMSO-d
6
) δ 1.1-1.3
H, 5.00; N, 29.77. Found: C, 42.80; H, 5.05; N, 29.67. When
other diamines 13 were employed, experiments were carried
out in a similar way.
(
br, 1H), 1.4-1.8 (br, 6H), 2.0-2.1 (br, 1H), 3.5-3.7 (br, 1H),
13
3
.8-4.0 (br, 1H), 8.27 (s, 1H), 8.49 (br s, 2H); C NMR could
not be measured because of low concentration of the sample;
2
,3-Dihydro-1-ethyl-2-methyl-6-nitro-1H-1,4-diaze-
+
MS (FAB) 196 (M + 1, 100%). Anal. Calcd for C
5.37; H, 6.71; N, 21.52. Found: C, 55.04; H, 6.71; N, 21.86.
trans-5a,6,7,8,9,9a-Hexahydro-3-nitro-1H-benzo[b][1,4]-
diazepine (14e). White powder; mp 216-217 °C. IR (KBr/
9 13 3 2
H N O : C,
-1
pine (14b). Yellow powder; mp 84-85 °C. IR (KBr/cm ) 1589,
5
1
1
3
8
(
(
4
377; H NMR (400 MHz, CDCl
.2-3.8 (br, 2H), 3.58 (q, J ) 7.2 Hz, 2H), 3.8-4.1 (br, 2H),
.51 (s, 1H), 8.73 (s, 1H); 13C NMR (100 MHz, CDCl
) δ 14.0
3
) δ 1.38 (t, J ) 7.2 Hz, 3H),
3
-1
1
cm ) 1573, 1311; H NMR (400 MHz, DMSO-d
6
) δ 1.1-1.3
q), 53.5 (t), 54.0 (t), 56.0 (t), 123.3 (s), 149.0 (d), 155.3 (d); MS
(
2
br, 2H), 1.3-1.5 (br, 2H), 1.6-1.8 (br, 2H), 2.2-2.3 (br, 2H),
+
FAB) 170 (M + 1, 100%). Anal. Calcd for C
9.70; H, 6.55; N, 24.84. Found: C, 49.86; H, 6.59; N, 24.51.
,3-Dihydro-2-methyl-6-nitro-1H-1,4-diazepine (14c).
7
H
11
3
N O
2
: C,
13
.9-3.1 (br, 2H), 8.30 (s, 1H), 8.37 (br s, 2H); C (100 MHz,
DMSO-d
6
) δ 23.4 (t), 33.7 (t), 61.5 (d), 121.1 (s), 149.1 (d); MS
2
+
(
5
FAB) 196 (M + 1, 100%). Anal. Calcd for C
9
H
13
3
N O
2
: C,
-1
Pale yellow powder; mp 170-171 °C. IR (KBr/cm ) 1567, 1295;
5.37; H, 6.71; N, 21.52. Found: C, 55.30; H, 6.63; N, 21.82.
1
H NMR (400 MHz, DMSO-d
6
) δ 1.20 (d, J ) 3.8 Hz, 3H), 3.2-
3
.4 (br, 1H), 3.62 (d, J ) 4.4 Hz, 2H), 8.41 (s, 1H), 8.51 (s,
JO0488513
8386 J. Org. Chem., Vol. 69, No. 24, 2004