1,2,5,6-Naphthalenetetramine (1a), its 1,4,5,8-isomer (2a), and their salts are valuable precursors for synthesizing nitrogen-containing arenes and other targets of interest. We describe how salts of tetramines 1a and 2a can be made from simple protected derivatives of 1,5-naphthalenediamine (2d) by sequences of regioselective dinitration, deprotection, and reduction. Various shortcomings of previously reported syntheses of tetramines 1a and 2a can thereby be avoided. In addition, we report structural studies that may help clarify the mechanism of nitration and resolve an earlier controversy about the regioselectivity observed in nitrations of derivatives of 1,5-naphthalenediamine (2d).
1,2,5,6-Naphthalenetetramine (1a), its 1,4,5,8-isomer (2a), and their salts are valuable precursors for synthesizing nitrogen-containing arenes and other targets of interest. We describe how salts of tetramines 1a and 2a can be made from simple protected derivatives of 1,5-naphthalenediamine (2d) by sequences of regioselective dinitration, deprotection, and reduction. Various shortcomings of previously reported syntheses of tetramines 1a and 2a can thereby be avoided. In addition, we report structural studies that may help clarify the mechanism of nitration and resolve an earlier controversy about the regioselectivity observed in nitrations of derivatives of 1,5-naphthalenediamine (2d).
1,2,5,6-Naphthalenetetramine
(1a), its n class="Chemical">1,4,5,8-isomer
(2a), and their salts are useful as precursors of novel
polymers,[1,2] azaarenes,[3] and
other structures of interest.[4−9] In particular, tetramines 1a and 2a can
be converted into bis(thiadiazole) 3(10−12) and bis(thiadiazine) 4,[6,7] respectively, which are related to compounds
that have been widely incorporated in π-conjugated polymers
and to small molecules used in luminescent materials and in thin-film
optoelectronic devices, including light-emitting diodes, solar cells,
field-effect transistors, and biosensors.[13−23]
Unfortunately, previously published
syntheses of naphthalenetetramines 1a and 2a have multiple undesirable features,
and controversy has arisen about certain structural assignments. In
particular, n class="Chemical">1,4,5,8-naphthalenetetramine (2a) and its
salts have been prepared by reducing 1,4,5,8-tetranitronaphthalene
(2b),[24−27] an explosive compound produced in low yield by the dinitration of
1,5-dinitronaphthalene (2c), along with significant amounts
of other nitrated products that must be separated. Another potential
way to make tetramine 2a is by dinitration of suitably
protected derivatives of 1,5-naphthalenediamine (2d), followed by deprotection and reduction. In 1985, Nielsen et al.
reported that the bis(4-methylbenzenesulfonamide) of 1,5-naphthalenediamine
(compound 2e)[28,29] reacted with HNO3/NaNO2 to give primarily the corresponding 4,8-dinitro
derivative 2f. Subsequent hydrolysis was alleged to produce
4,8-dinitro-1,5-naphthalenediamine (2g) in high yield.[30] Similarly, Nielsen et al. reported that the
related dinitration of bis(acetamide) 2h(31) gave mainly the 4,8-dinitro derivative 2i,
but their subsequent attempts to deprotect the dinitrated bis(acetamide)
by hydrolysis were unsuccessful.[24,30]
More
recent work by Sorokin et al. has suggested that dinitration
of bis(4-methylbenzenesulfonamide) 2e in fact gives the
n class="Chemical">2,6-dinitro derivative 1b,[24] which can be subjected to hydrolysis and reduction to give 1,2,5,6-naphthalenetetramine
(1a) in the form of its tetrahydrochloride salt.[1] In an alternative synthesis of tetramine 1a,[1] 2,6-dichloronaphthalene (1c), itself the product of a multistep synthesis, was nitrated
to give 2,6-dichloro-1,5-dinitronaphthalene (1d), which
was converted into 1,5-dinitro-2,6-naphthalenediamine (1e) by high-pressure amination and subsequently into the tetrahydrochloridesalt of tetramine 1a by reduction and treatment with
HCl.
We have re-examined the subject of 1,2,5,6-naphthalenetetramine
(1a), its n class="Chemical">1,4,5,8-isomer (2a), and their
salts. The goal of our work has been to eliminate uncertainty about
structural assignments, to provide new data that may help clarify
the mechanism of nitration of derivatives of 1,5-naphthalenediamine
(2d), and to find effective ways to make tetramines 1a and 2a without using explosive intermediates
and inconvenient reactions.
Results and Discussion
The bis(4-methylbenzenesulfonamide)
of 1,5-naphthalenediamine (compound 2e) was dinitrated
under the conditions (HNO3/NaNO2) used by Nielsen
et al.[30] and
later modified slightly by Sorokin and co-workers (Scheme ).[24] We isolated the product in 27% yield after purification by crystallization
from aqueous pyridine, and we confirmed that it was spectroscopically
identical to the compound obtained previously by Nielsen, Sorokin,
and their collaborators. However, Nielsen et al. reported that the
product was the 4,8-dinitrated isomer 2f, whereas Sorokin
et al. identified the compound as the 2,6-dinitrated isomer 1b. We crystallized the disputed product by cooling hot solutions
in tetrahydrofuran (THF), and analysis by X-ray diffraction confirmed
that dinitration occurs at the 2,6-positions to give compound 1b, as claimed by Sorokin et al. Crystallographic details
are provided in Table , and views of the structure appear in Figure .
Scheme 1
Table 1
Crystallographic Data for Compounds 1b, 2k, 5, and 6
compound
1b
2k
5
6
crystallization medium
THF
THF
THF
THF/hexane
formula
C24H20N4O8S2
C26H20N4O8
C28H28N4O9S2
C30H28N4O9
crystal system
monoclinic
monoclinic
triclinic
monoclinic
space group
C2/c
P21/c
P1̅
P21/c
a (Å)
25.4565(3)
21.374(2)
9.2281(3)
16.095(4)
b (Å)
5.6042(1)
5.9585(5)
10.7423(4)
21.593(5)
c (Å)
16.3639(2)
10.0311(8)
15.1969(5)
8.257(2)
α (deg)
90
90
81.895(2)
90
β (deg)
97.006(1)
92.402(4)
84.293(2)
101.741(11)
γ (deg)
90
90
76.469(2)
90
V (Å3)
2317.10(6)
1276.44(19)
1446.58(9)
2809.6(12)
Z
4
2
2
4
T (K)
100
150
150
150
ρcalc (g cm–3)
1.595
1.344
1.443
1.391
λ (Å)
1.54178
1.54178
1.34139
1.34139
μ (mm–1)
2.630
0.858
1.425
0.561
R1, I > 2σ(I) (all)
0.0318
0.1252
0.0355
0.0978
R1, all data
0.0323
0.1412
0.0416
0.1921
wR2, I > 2σ(I) (all)
0.0859
0.3727
0.0896
0.2271
wR2,
all data
0.0862
0.4018
0.0935
0.2893
measured reflections
22422
27338
34834
24254
independent reflections
2241
2425
6621
4070
observed reflections
2187
1850
5826
1961
Figure 1
Representations of the structure of crystals
of bis(4-methylbenzenesulfonamide) 1b grown from THF.
(a) View of the molecular conformation,
which is controlled in part by the formation of intramolecular N—H···O
hydrogen bonds involving the nitro and sulfonamide groups. (b) View
of the structure along the direction of π-stacked naphthyl cores
(b axis), showing how C—H···O
interactions link the stacks to form a layer. (c) View showing how
the packing of adjacent layers (red and blue) is directed by interdigitated
tolyl groups and additional C—H···O interactions
involving nitro and methyl groups. Unless otherwise indicated, atoms
of carbon are shown in gray, atoms of hydrogen in white, atoms of
nitrogen in blue, atoms of oxygen in red, and atoms of sulfur in yellow.
N—H···O hydrogen bonds and C—H···O
interactions are represented by broken lines.
Representations of the structure of crystals
of bis(4-methylbenzenesulfonamide) 1b grown from n class="Chemical">THF.
(a) View of the molecular conformation,
which is controlled in part by the formation of intramolecular N—H···O
hydrogen bonds involving the nitro and sulfonamide groups. (b) View
of the structure along the direction of π-stacked naphthyl cores
(b axis), showing how C—H···O
interactions link the stacks to form a layer. (c) View showing how
the packing of adjacent layers (red and blue) is directed by interdigitated
tolyl groups and additional C—H···O interactions
involving nitro and methyl groups. Unless otherwise indicated, atoms
of carbon are shown in gray, atoms of hydrogen in white, atoms of
nitrogen in blue, atoms of oxygen in red, and atoms of sulfur in yellow.
N—H···O hydrogen bonds and C—H···O
interactions are represented by broken lines.
The observed conformation of bis(4-methylbenzenesulfonamide) 1b (Figure a) is determined in part by a conspicuous pair of intramolecular
N–H···O n class="Chemical">hydrogen bonds (2.24 Å) involving
the sulfonamide and nitro groups. As expected, the 4-methylbenzenesulfonyl
groups are forced out of the plane of the naphthyl core, and the sulfonamidenitrogen atoms are notably pyramidalized (Σangles at N = 344°). This is a characteristic property of related sulfonamides
such as N-phenyl(4-methylbenzenesulfonamide).[32] In addition, the nitro groups are twisted by
34° out of the plane of the core. The naphthyl cores of compound 1b are aligned along the b axis to form parallel
columns of slipped π-stacks with a separation of 3.58 Å
between mean planes. Adjacent columns are linked to form layers by
C—H···O interactions (2.49 Å, as measured
by H···O distance) involving sulfonyl groups and hydrogen
atoms of the naphthyl units (Figure b). Packing of the layers is directed by interdigitated
4-methylphenyl groups and additional C—H···O
interactions (2.48 and 2.53 Å, as measured by H···O
distances) involving nitro and methyl groups (Figure c).
With the structure of the product
of dinitration firmly established,
the method of Nielsen, Sorokin, and their collaborators provides a
reliable way to make compound 1b. Although the yield
is low, the product can be obtained in pure form by a simple procedure.
Careful chromatographic separation of all products of nitration also
yielded minor dinitro compound 5, and analysis of the
total crude product by NMR spectroscopy indicated that the yields
of major iomer 1b and minor isomer 5 were
45 and 20%, respectively, before isolation. Crystallization of compound 5 from n class="Chemical">THF yielded a solvate of composition 5·1 THF, and its structure was determined by X-ray crystallography.
Crystallographic details are summarized in Table , and views of the structure are presented
in Figure .
Figure 2
Representations
of the structure of crystals of solvate 5·1 THF
grown from THF. (a) View of the distorted molecular conformation
of compound 5, which is controlled in part by the formation
of a single intramolecular N—H···O hydrogen
bond involving a nitro group and a sulfonamide group. (b) View of
the dimer held together by N—H···O hydrogen
bonds and C—H···O interactions, with hydrogen-bonded
guest molecules of THF shown in red. (c) View showing how each molecule
interacts with the next dimer in the same stack (red) and with a molecule
in an adjacent stack of dimers (blue) by forming C—H···O
interactions involving sulfonyl groups. Unless otherwise indicated,
atoms of carbon are shown in gray, atoms of hydrogen in white, atoms
of nitrogen in blue, atoms of oxygen in red, and atoms of sulfur in
yellow. N—H···O hydrogen bonds and C—H···O
interactions are represented by broken lines.
Representations
of the structure of crystals of solvate 5·1 THF
grown from n class="Chemical">THF. (a) View of the distorted molecular conformation
of compound 5, which is controlled in part by the formation
of a single intramolecular N—H···O hydrogen
bond involving a nitro group and a sulfonamide group. (b) View of
the dimer held together by N—H···O hydrogen
bonds and C—H···O interactions, with hydrogen-bonded
guest molecules of THF shown in red. (c) View showing how each molecule
interacts with the next dimer in the same stack (red) and with a molecule
in an adjacent stack of dimers (blue) by forming C—H···O
interactions involving sulfonyl groups. Unless otherwise indicated,
atoms of carbon are shown in gray, atoms of hydrogen in white, atoms
of nitrogen in blue, atoms of oxygen in red, and atoms of sulfur in
yellow. N—H···O hydrogen bonds and C—H···O
interactions are represented by broken lines.
As in the case of bis(4-methylbenzenesulfonamide) 1b, the conformation of isomer 5 is determined in part
by interaction of the adjacent n class="Chemical">sulfonamide and nitro groups, but only
one intramolecular N—H···O hydrogen bond (2.32
Å) is formed (Figure a). Introducing a nitro group at the 4-position significantly
distorts the naphthalene core and produces a torsional angle of 174°
along C1—C9—C10—C5. In addition, C—N bonds at the 4- and 5-positions
are tilted out of the average plane of the core by 13 and 7°,
respectively, in opposite directions. Pyramidalization of the sulfonamidenitrogen atoms (Σangles at N = 348 and
337°) is similar to that observed in isomer 1b,
and the 4-methylbenzenesulfonyl groups are again forced out of the
plane of the naphthyl core. Twisting of the nitro groups out of the
plane of the core is accentuated at the 4-position (55°), whereas
the value at the 2-position (27°) resembles the one observed
for isomer 1b.
As shown in Figure b, molecules of compound 5 form
dimers associated along
the b axis by N–H···O hydrogen
bonds involving n class="Chemical">sulfonamide units (2.94 Å), as well as by offset
π-stacking (3.41 Å between mean planes). The association
is strengthened by C—H···O interactions between
hydrogen atoms bonded to the naphthyl core and both a nitro group
(2.65 Å) and a sulfonyl group (2.56 Å). The dimers are further
linked to form stacks along the b axis by reciprocal
C—H···O interactions (2.39 Å) involving
4-methylbenzenesulfonyl groups (Figure c). Finally, adjacent stacks are linked by reciprocal
C—H···O interactions (2.35 Å) involving
the 4-methylbenzenesulfonyl groups (Figure c), as well as by other C—H···O
interactions. Guest molecules of THF are ordered and form N—H···O
hydrogen bonds (2.77 Å) with sulfonamide groups (Figure b).
The bis(benzyl carbamate)
of n class="Chemical">1,5-naphthalenediamine (compound 2j) reacted more
slowly with HNO3/NaNO2 than the corresponding
bis(4-methylbenzenesulfonamide) 2e, and dinitration was
therefore carried out at 25 °C, followed
by a period of heating at 100 °C (Scheme ). The major product was obtained as yellow
needles in 18% yield after crystallization from THF. Analysis of the
crystals by X-ray diffraction established that dinitration occurred
at the 4- and 8-positions to give compound 2k. Crystallographic
data are presented in Table , and views of the structure are shown in Figure .
Scheme 2
Figure 3
Representations of the
structure of crystals of bis(benzyl carbamate) 2k grown
from THF. (a) View of the distorted molecular conformation
of compound 2k. (b) View showing that the structure can
be considered to be composed of layers in which each molecule of compound 2k is linked to four neighbors by four N—H···O
hydrogen bonds involving the carbamoyl groups. The central molecule
is shown in red, and hydrogen bonds are represented by broken lines.
(c) View along the c axis showing two adjacent layers,
with one highlighted in red. Unless otherwise indicated, atoms of
carbon are shown in gray, atoms of hydrogen in white, atoms of nitrogen
in blue, and atoms of oxygen in red.
Representations of the
structure of crystals of bis(benzyl carbamate) 2k grown
from n class="Chemical">THF. (a) View of the distorted molecular conformation
of compound 2k. (b) View showing that the structure can
be considered to be composed of layers in which each molecule of compound 2k is linked to four neighbors by four N—H···O
hydrogen bonds involving the carbamoyl groups. The central molecule
is shown in red, and hydrogen bonds are represented by broken lines.
(c) View along the c axis showing two adjacent layers,
with one highlighted in red. Unless otherwise indicated, atoms of
carbon are shown in gray, atoms of hydrogen in white, atoms of nitrogen
in blue, and atoms of oxygen in red.
The conformation of bis(benzyl carbamate) 2k shows
that tetrasubstitution at the 1,4,5,8-positions causes significant
distortions (Figure a). The naphthyl core is planar, and the atoms of n class="Chemical">nitrogen all adopt
normal sp2 hybridization. However, C—N bonds to
the nitro groups are tilted out of the plane of the core by 17°,
and C—N bonds to the carbamate groups are tilted in the opposite
direction by 13°. Moreover, the nitro and carbamate groups are
twisted out of the plane of the naphthyl core by 57 and 50°,
respectively. The relatively high values of R shown
in Table reflect
disorder of the benzyl groups over two positions. Molecules of compound 2k associate to form layers held together in part by N—H···O
hydrogen bonds (2.79 Å), which are a characteristic feature of
the structures of related benzyl carbamates (Figure b).[33] Packing
of adjacent layers is controlled by weak interactions of the benzyl
groups (Figure c).
Although 2,6-dinitration of n class="Chemical">bis(4-methylbenzenesulfonamide) 2e to give compound 1b could be accomplished
at 25 °C under the standard conditions (HNO3/NaNO2), 4,8-dinitration of bis(carbamate) 2j to produce
compound 2k required heating at 100 °C. A similar
reaction carried out at 25 °C led to the formation of mononitro
derivative 7 in 65% yield (Scheme ). The distorted structure of 4,8-dinitro
derivative 2k suggests that introduction of the first
nitro group is facile but forces the adjacent carbamate group further
out of the plane of the naphthyl core, leading to deactivation that
makes dinitration difficult. Indeed, conversion of compound 7 into dinitrated product 2k under the standard
conditions (HNO3/NaNO2) required higher temperatures
(Scheme ).
4,8-Dinitro
compound 2k can be obtained in pure form
by a simple method, so our procedure is useful, and the structure
of the compound has been confirmed unambiguously. However, the yield
is low, so we examined the crude product of direct dinitration at
100 °C in greater detail. n class="Chemical">Mononitro compound 7 was
formed efficiently under milder conditions and can be converted into
4,8-dinitro derivative 2k at higher temperatures, suggesting
that it is an intermediate in further nitration. Subsequent crystallization
of the crude product remaining after removing symmetric dinitro isomer 2k produced a 1:1 THF solvate of 2,8-dinitro isomer 6, which was isolated in 15% yield. Although dinitration of
bis(benzyl carbamate) 2j gave compounds 2k and 6 in low yields (18 and 15%, respectively), the
products could be isolated in pure crystalline form without chromatographic
separation. Moreover, when the crude product of dinitration was examined
by 1H NMR spectroscopy, compounds 2k and 6 were detected in yields of about 35 and 30%, respectively,
and no other significant product was formed.
The structure assigned
to 2,8-dinitro compound 6 was
confirmed by X-ray crystallography. Views of the structure appear
in Figure , and additional
crystallographic data are summarized in Table . As observed in the structures of n class="Chemical">dinitro
compounds 1b, 2k, and 5, which
have patterns of 1,2,5,6-, 1,4,5,8-, and 1,2,4,5-tetrasubstitution,
respectively, the 1,2,5,8-tetrasubstitution found in bis(benzyl carbamate) 6 also causes significant molecular distortions (Figure a). In particular,
the torsional angle defined by C1—C9—C10—C5 in the naphthyl core is 173°,
and the nitro and carbamate groups are twisted out of the average
plane. Molecules of compound 6 are linked to form columns
parallel to the c axis, both by N—H···O
hydrogen bonds (2.91 Å) between carbamoyl units and by offset
π-stacking with a separation of 3.65 Å between mean planes
(Figure b). Packing
of adjacent columns is determined by various weak interactions. Guest
molecules of THF form N—H···O hydrogen bonds
(2.75 Å) with carbamoyl groups (Figure b). The relatively high values of R shown in Table reflect disorder of the benzyl groups.
Figure 4
Representations of the
structure of crystals of bis(benzyl carbamate) 6 grown
from THF/hexane. (a) View of the distorted conformation
of compound 6, with only one orientation of the disordered
benzyl groups drawn. (b) View showing part of a column of hydrogen-bonded
and π-stacked molecules. Guest molecules of THF appear in red.
Unless otherwise indicated, atoms of carbon are shown in gray, atoms
of hydrogen in white, atoms of nitrogen in blue, and atoms of oxygen
in red.
Representations of the
structure of crystals of bis(benzyl carbamate) 6 grown
from n class="Chemical">THF/hexane. (a) View of the distorted conformation
of compound 6, with only one orientation of the disordered
benzyl groups drawn. (b) View showing part of a column of hydrogen-bonded
and π-stacked molecules. Guest molecules of THF appear in red.
Unless otherwise indicated, atoms of carbon are shown in gray, atoms
of hydrogen in white, atoms of nitrogen in blue, and atoms of oxygen
in red.
The mechanism of electrophilic
aromatic nitration continues to
be debated. In certain cases, it may involve direct reaction of NO2+ with the substrate to form a classic Wheland
intermediate. However, suitably activated aromatic compounds can also
undergo nitration by a radical pathway initiated by electron transfer
from the substrate to n class="Chemical">NO2+,[34−39] followed by coupling of the resulting aromatic radical cation with
NO2 to form a σ-bonded intermediate. In such cases,
the position of nitration is dictated by the combined effects of nonuniform
spin density in the aromatic radical cation and the stability of the
intermediate. The regioselectivity of radical nitrations can thereby
depend on the identity of substituents in subtle and unexpected ways.
The observed preferences for 2,6-dinitration (in the case of bis(4-methylbenzenesulfonamide) 2e) and for 4,8-dinitration (in the case of bis(carbamate) 2j) presumably arise because the reactions occur by different
mechanisms or because they both follow radical pathways, but the radical
cations initially formed differ significantly in structure and distribution
of spin density.
The yields of compounds 1b, 2k, 5, and 6 are not high, but all
are easily isolated
in pure form by crystallization, their structures are firmly established,
and sequences of deprotection and reduction allow preparation of 1,2,5,6-
and 1,4,5,8-naphthalenetetramines 1a and 2a, as well as less symmetric isomers (Scheme ). Dinitrated n class="Chemical">bis(4-methylbenzenesulfonamide) 1b was deprotected in 93% yield by using H2SO4 as described by Nielsen et al.,[30] and the product 1e was subsequently reduced by SnCl2 to give the tetrahydrochloride salt of tetramine 1a in 79% yield. Dinitrated bis(carbamate) 2k was deprotected
in 88% yield by using BBr3, and the product 2g was then reduced by SnCl2 to give the tetrahydrochloridesalt of tetramine 2a in 55% yield. The salt was identified
as the tetrahydrochloride on the basis of its elemental analysis,
the composition of closely related salts,[40] and thermogravimetric analysis. Isolation of both naphthalenetetramines
as their salts is an example of a widely used strategy that avoids
the need to work with highly air-sensitive free bases.[41]
Scheme 3
Conclusions
1,2,5,6-Naphthalenetetramine
(1a), its n class="Chemical">1,4,5,8-isomer
(2a), and their salts are valuable precursors for synthesizing
nitrogen-containing arenes and other targets of interest. We have
found that salts of tetramines 1a and 2a can be made from simple protected derivatives of 1,5-naphthalenediamine
(2d) by sequences of regioselective dinitration, deprotection,
and reduction. Various shortcomings of previously reported syntheses
of tetramines 1a and 2a can thereby be avoided.
In addition, our studies provide new data that may help clarify the
mechanism of nitration and resolve an earlier controversy about the
regioselectivity observed in nitrations of 1,5-naphthalenediamine
(2d).
Experimental Section
All reagents
and solvents were obtained from commercial sources
and used without further purification unless otherwise indicated.
Compounds 1b(24,30) and 1e(24,30) were prepared by published procedures.
The compound
was synthesized by a modification of the
method reported by Festel et al.[42] Solutions
of Na2CO3 (6.83 g, 64.4 mmol) in n class="Chemical">water (80 mL)
and benzyl chloroformate (9.1 mL, 64 mmol) in dichloromethane (120
mL) were added to a solution of 1,5-naphthalenediamine (4.01 g, 25.4
mmol) in dichloromethane (400 mL). The mixture was stirred at 25 °C
for 12 h, and then volatile components were removed by partial evaporation
under reduced pressure to give a suspension. The off-white solid was
separated by filtration, washed with water, and crystallized from
hot dioxane to afford bis(phenylmethyl) 1,5-naphthalenediylcarbamate
as colorless needles (2j; 9.10 g, 21.4 mmol, 84%).
A solution prepared by adding aqueous HNO3 (70%, 3.5 mL) to acetic acid (50 mL) was added to a solution
of bis(phenylmethyl) 1,5-naphthalenediylcarbamate (2j; 1.02 g, 2.39 mmol) and NaNO2 (0.053 g, 0.77 mmol) in
acetic acid (50 mL). The mixture was stirred at 25 °C for 20
h and then at 100 °C for 3 h. The resulting suspension was cooled
to 25 °C, treated with water, and filtered. The recovered solid
was washed with water, washed with acetone, and crystallized from
hot THF to give bis(phenylmethyl) 4,8-dinitro-1,5-naphthalenediylcarbamate
as a pale yellow solid (2k; 0.222 g, 0.430 mmol, 18%):
mp 255 °C dec; FTIR (ATR) 3273, 3064, 3041, 1516, 1702, 1515,
1499, 1244, 1228, 1144, 1075 cm–1; 1H
NMR (400 MHz, DMSO-d6) δ 9.81 (s,
2H), 8.16 (d, 3J = 8 Hz, 2H), 7.72 (d, 3J = 8 Hz, 2H), 7.39 (m, 10H), 5.13 (s, 4H); 13C NMR (100 MHz, DMSO-d6) δ
155.1, 146.2, 137.2, 136.1, 129.2, 128.8, 128.5, 127.6, 125.3, 123.8,
67.0; HRMS (ESI, TOF) calcd for C26H20N4O8 + NH4+m/e 534.1619, found 534.1626. Anal. calcd for C26H20N4O8: C, 60.47; H, 3.90; N, 10.85. Found: C,
60.31; H, 3.86; N, 10.88.A solution prepared by adding aqueous HNO3 (70%, 2.4 mL) to acetic acid (35 mL) was added to a solution
of bis(phenylmethyl) 4-nitro-1,5-naphthalenediylcarbamate (7; 675 mg, 1.43 mmol) and NaNO2 (35 mg, 0.51 mmol) in acetic
acid (10 mL). The mixture was stirred at 100 °C for 3 h. The
resulting suspension was then cooled to 25 °C, treated with water,
and filtered. The recovered solid was washed with water, washed with
acetone, and crystallized from hot THF to provide bis(phenylmethyl)
4,8-dinitro-1,5-naphthalenediylcarbamate as a pale yellow solid (2k; 163 mg, 0.315 mmol, 22%).
Bis(phenylmethyl) 1,5-naphthalenediylcarbamate
(2j) was dinitrated at 100 °C under conditions described
above, and the acetone extracts produced during purification of the
primary product were subjected to evaporation under reduced pressure.
The residue was dissolved in THF, and layering hexane over the solution
induced crystallization of bis(phenylmethyl) 2,8-dinitro-1,5-naphthalenediylcarbamate
in the form of yellow needles (6; 0.185 g, 0.358 mmol,
15%): mp 185 °C dec; FTIR (ATR) 3287, 3145, 3032, 2952, 2885,
2058, 2005, 1736, 1703, 1523, 1210 cm–1; 1H NMR (400 MHz, CDCl3) δ 8.18 (d, 3J = 8 Hz, 1H), 7.99 (d, 3J =
9 Hz, 1H), 7.92–7.88 (m, 2H), 7.72 (s, 1H), 7.52 (s, 1H), 7.46–7.35
(m, 10H), 5.29 (s, 2H), 5.07 (s, 2H); 13C NMR (100 MHz,
CDCl3) δ 153.5, 145.4, 145.2, 137.1, 135.3, 135.2,
129.0, 128.9 (2C), 128.8 (2C), 128.7, 128.6, 128.4, 127.2, 125.8,
123.4, 122.1, 121.1, 119.0, 68.7, 68.4; HRMS (ESI, TOF) calcd for
C26H20N4O8 + NH4+m/e 534.1619, found 534.1623.
4,8-Dinitro-1,5-naphthalenediamine
(2g)
A suspension of bis(phenylmethyl) 4,8-dinitro-1,5-naphthalenediylcarbamate
(2k; 322 mg, 0.623 mmol) indichloromethane (15 mL) was
stirred at 0 °C and treated dropwise with a solution of BBr3 (1.0 M, 1.3 mL, 1.3 mmol) in dichloromethane. The resulting
suspension was stirred at 25 °C for 3 h, treated with water,
and stirred for 15 min. Volatiles were removed by evaporation under
reduced pressure, and the residual solid was washed with water and
dried under vacuum to give 4,8-dinitro-1,5-naphthalenediamine as a
red solid (2g; 136 mg, 0.548 mmol, 88%). Further purification
was achieved by crystallization from hot absolute ethanol: mp 230
°C dec; FTIR (ATR) 3431, 3343, 3257, 3065, 3041, 1516, 1454,
1247 cm–1; 1H NMR (400 MHz, DMSO-d6) δ 8.02 (d, 3J = 9 Hz, 2H), 6.84 (d, 3J = 9 Hz, 2H),
6.55 (s, 4H); 13C NMR (100 MHz, DMSO-d6) δ 149.5, 135.9, 128.9, 115.5, 110.1; HRMS (APCI,
TOF) calcd for C10H8N4O4 – H m/e 247.0473, found 247.0453.
A mixture
of 4,8-dinitro-1,5-naphthalenediamine
(2g; 106 mg, 0.427 mmol) and n class="Chemical">SnCl2·2
H2O (972 mg, 4.30 mmol) in ethanol (7.5 mL) and concentrated
aqueous HCl (2.5 mL) was stirred at 90 °C under N2 for 12 h and then cooled to 0 °C. The resulting suspension
was filtered, and the recovered solid was washed with HCl and dried
under vacuum to afford crude 1,4,5,8-naphthalenetetramine tetrahydrochloride
as an off-white solid (2a·4 HCl; 78 mg, 0.23 mmol,
55%). Further purification could be accomplished by dissolving the
product in water and adding the solution to concentrated aqueous HCl.
The salt was stored under dry N2: mp 100 °C dec; FTIR
(ATR) 3034, 2905, 2817, 2728, 2693, 2587, 2532, 1125, 629 cm–1; 1H NMR (400 MHz, DMSO-d6) δ 7.12 (s, 4H), 3.59 (br s, 12H); 13C NMR (100
MHz, DMSO-d6) δ 131.8, 122.2, 118.6;
HRMS (ESI, TOF) calcd for C10H12N4 + H+m/e 189.1135, found 189.1135. Anal.
calcd for C10H16Cl4N4:
C, 35.95; H, 4.83; N, 16.77. Found: C, 35.95; H, 4.80; N, 15.93.
A mixture of 2,6-dinitro-1,5-naphthalenediamine
(13; 1.02 g, 4.11 mmol) and SnCl2·2 H2O (9.05 g, 40.1 mmol) in ethanol (40 mL) and concentrated
aqueous HCl (12 mL) was stirred at 90 °C under N2 for
12 h and then cooled to 0 °C. The resulting suspension was filtered,
and the recovered solid was washed with HCl and dried under vacuum
to provide crude 1,2,5,6-naphthalenetetramine tetrahydrochloride as
a beige solid. The product was then dissolved in water (∼100
mL), and the solution was poured into warm, vigorously stirred concentrated
aqueous HCl (∼100 mL). The mixture was cooled to 25 °C,
and the resulting suspension was cooled further to 0 °C. The
precipitated solid was separated by filtration, washed with HCl, and
dried under vacuum to afford a purified sample of 1,2,5,6-naphthalenetetraminetetrahydrochloride (1a·4 HCl; 1.08 g, 3.23 mmol,
79%). The salt was stored under dry N2. 1H NMR
(400 MHz, DMSO-d6) δ 7.50 (d, 3J = 9 Hz, 2H), 7.23 (d, 3J = 9 Hz, 2H), 4.17 (br s, 12H). Additional characterization
was reported by Stille and co-workers.[1]
Scheme 1
Figure 1
Figure 2
Scheme 2
Figure 3
Figure 4
Scheme 3