2,3,5,6-Tetraaminopyridine tetracarbamate from dinicotinic acid

Article abstract of DOI:10.1080/00397910701865942

The tetraethylcarbamate of 2,3,5,6-tetraaminopyridine was synthesized using dinicotinic acid as starting material in 10 steps with 23% overall yield. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397910701865942

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2,3,5,6‐Tetraaminopyridine Tetracarbamate
from Dinicotinic Acid
Matthew C. Davis a & David J. Irvin a
a Chemistry and Materials Division, Michelson Laboratory , Naval Air Warfare
Center , China Lake, California, USA
Published online: 17 Apr 2008.
To cite this article: Matthew C. Davis & David J. Irvin (2008) 2,3,5,6‐Tetraaminopyridine Tetracarbamate
from Dinicotinic Acid, Synthetic Communications: An International Journal for Rapid Communication of
Synthetic Organic Chemistry, 38:8, 1159-1167, DOI: 10.1080/00397910701865942
To link to this article: http://dx.doi.org/10.1080/00397910701865942
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Synthetic Communicationsw, 38: 1159–1167, 2008
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910701865942
2,3,5,6-Tetraaminopyridine
Tetracarbamate from Dinicotinic Acid
Matthew C. Davis and David J. Irvin
Chemistry and Materials Division, Michelson Laboratory, Naval Air
Warfare Center, China Lake, California, USA
Abstract: The tetraethylcarbamate of 2,3,5,6-tetraaminopyridine was synthesized
using dinicotinic acid as starting material in 10 steps with 23% overall yield.
Keywords: Amino, Curtius rearrangement, hydrogenation, nitration, pyridine
Polymer matrix composites (PMC) are generally lighter and stronger than
either conventional polymers or metals.[1] The highest modulus manmade
fiber is composed of M5w, a polypyridobisimidazole.[2–9] M5w is a product
of Magellan Systems International, LLC, a subsidiary of E. I. du Pont de
Nemours and Company. PMCs that incorporate these types of fibers may
have applications in military and aerospace designs such as aircraft
fuselage, naval ship hulls, and body armor. An important monomer used in
the preparation of high-performance polymers is 2,3,5,6-tetraaminospyridine
(TAP), which suffers from extreme sensitivity to air oxidation. This makes
isolation and purification of TAP challenging and can lead to polymers with
suboptimal properties.
The typical synthesis of TAP, which is isolated as its trihydrochloride salt,
is shown in Scheme 1.[10–13] The reasons for TAP’s instability is not under-
stood, but its reactivity is instructive. Gerber[5] and Arnold[8] have shown
Received in the USA November 14, 2007
Address correspondence to Matthew C. Davis, Chemistry and Materials Division,
Michelson Laboratory, Naval Air Warfare Center, China Lake, CA 93555, USA.
E-mail: matthew.davis@navy.mil
1159

1160
M. C. Davis and D. J. Irvin
Scheme 1. Reagents and conditions: (a) conc. H2SO4, HNO3; (b) Sn, HCl, H2O.
that reaction of TAP trihydrochloride with acetyl chloride or para-toluenesul-
fonyl chloride yields the 3,5-acetamido- or 3,5-(para-toluene)sulfonamido-
TAP derivatives in excellent yield. Furthermore, these products could be
recrystallized, yielding white solids with sharp melting points and accurate
combustion analyses. With the commercial availability and shelflife of 2,6-
diaminopyridine, clearly the free amino groups at the 3,5-positions largely
account for TAP’s air sensitivity.
We sought to synthesize TAP in a manner whereby all the intermediates
are shelf stable. The final product would be a protected TAP that is shelf stable
and recrystallizable with protecting groups that are typically cleaved under the
conditions of polymerization. The basic strategy was to reverse the sequence
of reactions in Scheme 1, that is, install the amino groups at positions 3 and 5
of pyridine first. In the second stage, the amino groups at positions 2 and 6
would be added. A general reaction sequence that was anticipated to work
was A ! B ! C ! D (Scheme 2).
Attempts to prepare 3,5-diaminopyridine directly from 3,5-dibromopyri-
dine by the procedure of Maier–Bode were unsuccessful.[14] Following the
method of Meyer and Tropsch, N,N0-(diethoxycarbonyl)-3,5-diaminopyridine
(4) was prepared by a double Curtius reaction on dinicotinic acid (1)
(Scheme 3).[15] Preliminary attempts to nitrate 4 with excess 100% nitric
acid in concentrated sulfuric acid gave not the desired 2,6-dinitro derivative
but the 2-nitro derivative 5 in good yield.[16] This was disappointing since
3,5-dialkoxypyridines have been dinitrated at the 2,6-positions.[13,17,18]
However, an exhaustive search for conditions that would yield the dinitro
was not undertaken. Continuing onward, catalytic hydrogenation of 5 gave
the amine 6 in quantitative yield. This amine remained a white solid after 1
year of storage at room temperature in air. Amine 6 could be acetylated
with acetic anhydride to give 7 or carbamylated with ethyl chloroformate to
give 8.[19]
With the tricarbamate 8 in hand, a second sequence of nitration/
reduction/carbamylation was carried out. Nitration of 8 gave mononitro 9
Scheme 2. Pg ¼ protecting group.

2,3,5,6-Tetraaminopyridine Tetracarbamate
1161
Scheme 3. Reagents and conditions: (a) SOCl2, reflux; (b) N2H4, EtOH, reflux; (c)
H2O, HCl, NaNO2, 10 8C; (d) EtOH, reflux; (e) conc. H2SO4, 100% HNO3; (f) H2,
Pd/C, EtOH; (g) Ac2O, reflux; (h) ClCO2Et, pyridine; (i) H2, Pd/C, DMF.
uneventfully. For catalytic hydrogenation of 9 it was necessary to use N,N-
dimethylformamide as solvent because the solubility of 10 was so poor in
common organic solvents. Amine 10 had a pale pink color that remained
constant when stored at room temperature in air for several days. Its nuclear
magnetic resonance spectra showed no noticeable decomposition. Finally,
carbamylation of 10 gave the tetracarbamate of TAP (11) in excellent yield. It
was only at this stage could we be certain that the aromatic substitutions were
not occurring at the 4-position of the pyridine nucleus. The carbon-13 nuclear
magnetic resonance spectrum of 11 shows only three peaks in the aromatic
region resulting from symmetrical substitution. The tetracarbamate 11 is
similar to the reported tetraacetamide of TAP.[20] It is soluble in common
organic solvents and showed no melting at temperatures less than 300 8C.
In conclusion, the unreported tetraethyltetracarbamate of 2,3,5,6-tetraa-
minopyridine was synthesized from dinicotinic acid in 10 steps with 23%
overall yield.
EXPERIMENTAL
Caution: The dinicotinoyl diazide intermediate 3 in the preparation of 4 is
potentially explosive. The ether extract should be evaporated with a room-
temperature (22 8C) water bath. The dinicotinoyl diazide should not be
stored but immediately dissolved in alcohol and rearranged.
Melting points were collected with a Mel-Temp II from Laboratory
Devices (Holliston, MA) and are not corrected. NMR data were obtained on

1162
M. C. Davis and D. J. Irvin
a Bru¨ker Avance-300 spectrometer (1H at 300 MHz, 13C at 75 MHz). NMR
data were processed using NUTS software from Acorn NMR, Inc.
(Livermore, CA). Spectra were referenced to solvent or tetramethylsilane
(TMS). Dinicotinic acid was purchased from Aldrich Chemical Co.
(Milwaukee), and all other reagents were obtained commercially and used
as received. Elemental analyses were performed by Atlantic Microlab, Inc.
(Norcross, GA).
3,5-Pyridinedicarbonyl Dichloride (1)
A 250-mL round-bottomed flask equipped with magnetic stirbar was charged
with 30 g of dinicotinic acid (0.18 mol) and 100 mL of SOCl2. The mixture
was refluxed under an N2 atmosphere. After 12 h, the mixture was a pale
yellow solution. The mixture was distilled at atmospheric pressure to
remove the SOCl2. Hexanes (50 mL) were added to the light orange oil
remaining in the pot. The colorless crystalline solid that precipitated was
filtered through a coarse-porosity glass frit. The beige crystals (29 g, 81%)
were more than 97% pure by NMR. The solid can be recrystallized from
hexanes. Mp 65–67 8C (lit.[3] 67–69 8C). dH (CDCl3): 9.55 (s, 2H), 9.02
(t, J ¼ 2.1, 1H); dC (CDCl3): 166.02, 156.44, 140.72, 130.19.
3,5-Pyridinedicarboxylic Acid Dihydrazide (2)
A 1-L round-bottomed flask equipped with magnetic stirbar was charged with
250 mL of EtOH and 16 mL of anhydrous N2H4 (15.76 g, 0.493 mol, 10
equiv). The mixture was cooled in an ice bath. In a separate flask, 10 g of 1
(0.049 mol) were added to vigorously stirred EtOH (50 mL). The mixture
became warm, and all the diacid dichloride dissolved. The latter solution
was poured in a steady stream into the hydrazine flask; some white solids pre-
cipitated. The mixture was refluxed for 12 h, after which time copious white
solids had precipitated. The mixture was cooled to rt, and 50 mL H2O were
added. The solids were collected on a coarse-porosity glass frit. The filter
cake was washed with 50 mL of EtOH and air-dried on the frit for 2 h. A
suitable solvent for recrystallization could not be found. The material was
more than 95% by NMR, and no further purification was performed (8.54 g,
89%). Mp 172–175 8C (dec.). dH (DMSO): 10.19 (bs, 2 NH), 9.07
(d, J ¼ 2.3 Hz, 2H), 8.61 (t, J ¼ 2.1 Hz, 1H), 5.03 (bs, 2 NH2); dC
(DMSO): 163.73, 150.09, 133.76, 128.74, 98.44.
N,N0-Di(ethoxycarbonyl)-3,5-diaminopyridine (4)
A 2-L round-bottomed flask equipped with magnetic stirbar was charged with
200 mL of H2O, 29 mL of conc. HCl (0.355 mol, 4 equiv), and 17.3 g 2

2,3,5,6-Tetraaminopyridine Tetracarbamate
1163
(0.088 mol). The mixture was allowed to stir at rt until all the solids dissolved
(ꢀ30 min). The mixture was cooled in an ice/NaCl bath to approx. 210 8C. A
previously prepared solution of 24 g of NaNO2 (0.28 mol, 3.2 equiv) in
50 mL of H2O was added dropwise. A white solid immediately began to
separate. After about 10 mL were added, stirring continued by swirling the
flask by hand. The addition was complete in 1 h and stirred at 210 8C for
another 20 min. Ether (1 L) was added, and the aqueous phase was
extracted, dissolving most of the white solid. The aqueous layer was further
extracted with 250 mL of Et2O. The organic phases were collected and
washed with 200 mL of H2O, then 200 mL of saturated aqueous NaHCO3,
and then 200 mL of brine. The organic phase was dried over MgSO4, and
the filtrate was poured into a 3-L round-bottomed flask and rotary evaporated
(10 torr, 22 8C), leaving a soft white solid. A sample of the crude dinicotinoyl
diazide (3) was taken for NMR [dH (CDCl3): 9.41 (d, J ¼ 2.0 Hz, 2H), 8.5
(t, J ¼ 2.0 Hz, 1H); dC (CDCl3): 170.33, 154.86, 137.56, 126.83], and then
1 L of EtOH and a magnetic stirbar were added to the flask. The dinicotinoyl
diazide (3) did not dissolve immediately. The flask was placed in a heating
mantle, and a reflux condenser with N2 bubbler was equipped. The mixture
was heated at reflux for 18 h. The pale yellow solution was rotary evaporated,
leaving 19.5 g of a pale yellow solid. The solid was slurried with 100 mL of
MeCN and filtered on a medium-porosity glass frit to give 18 g of the title
compound as a white amorphous solid (80%). NMR showed the material
was more than 95% pure product. It was recrystallized from EtOH to give
the title compound as a microcrystalline powder. Mp 191–193 8C (lit.[15]
179–181 8C). dH (CDCl3): 8.36 (d, J ¼ 2.1 Hz, 2H), 8.22 (t, J ¼ 2.1 Hz,
1H), 7.02 (bs, 2 NH), 4.26 (q, J ¼ 7.2 Hz, 4H), 1.33 (t, J ¼ 7.2 Hz, 6H); dH
(DMSO): 9.84 (bs, 2 NH), 8.28 (d, J ¼ 2.1 Hz, 2H), 8.18 (t, J ¼ 2.0 Hz,
1H), 4.14 (q, J ¼ 6.4 Hz, 4H), 1.24 (t, J ¼ 7.1 Hz, 6H); dC (DMSO):
153.55, 135.99, 133.71, 114.51, 60.52, 14.43. Elemental analysis calculated
for C11H15N3O4: C, 52.17; H, 5.97; N, 16.59. Found: C, 51.7; H, 5.93; N,
16.63.
2-Nitro-N,N0-di(ethoxycarbonyl)-3,5-diaminopyridine (5)
A 500-mL round-bottomed flask equipped with magnetic stirbar was charged
with 50 mL of conc. H2SO4, and the flask was cooled in an ice bath. Once the
acid was cold, 7.6 g of 4 (0.03 mol) were added in one portion. The cooling
bath was removed, and all the solids were allowed to dissolve (ꢀ30 min).
The flask was placed in the ice bath, and 4 mL of 100% HNO3 (0.09 mol, 4
equiv) were added dropwise in 5 min. The cooling bath was removed, and
the mixture was stirred at rt for 30 min, whereupon thin-layer chromatography
(TLC) showed all the starting material was consumed. The yellow reaction
mixture was poured onto 500 g of crushed ice and H2O. A pale yellow solid
precipitated. The mixture was extracted twice with 250-mL portions of

1164
M. C. Davis and D. J. Irvin
CHCl3. The combined extracts were washed with 200 mL of H2O and dried
over MgSO4. Rotary evaporation gave a crude pale yellow semisolid.
Toluene (25 mL) was added, and the mixture was agitated, causing the title
compound to crystallize. The solid was filtered and air dried on the frit
(6.67 g, 75%) and was sufficiently pure. The solid could be recrystallized
from toluene to give the title compound as tiny, pale yellow needles. Mp
129–132 8C. dH (CDCl3): 9.84 (bs, 1 NH), 9.25 (d, J ¼ 2.3 Hz, 1H), 8.36
(d, J ¼ 2.5 Hz, 1H), 7.15 (bs, 1 NH), 4.31 (q, J ¼ 7.1 Hz, 4H), 1.35 (td,
J ¼ 7.4 Hz and 2.5 Hz, 6H); dH (DMSO): 10.54 (bs, NH), 9.91 (bs, NH),
8.55 (d, J ¼ 2.3 Hz, 1H), 8.28 (d, J ¼ 2.1 Hz, 1H), 4.19 (q, J ¼ 7.2, 2H),
4.15 (q, J ¼ 7.2 Hz, 2H), 1.27 (t, J ¼ 6.7 Hz, 3H), 1.23 (t, J ¼ 6.7 Hz, 3H);
dC (DMSO): 153.27, 153.04, 142.38, 141.18, 131.97, 130.07, 118.88, 61.53,
61.25, 14.29. Elemental analysis calculated for C11H14N4O6: C, 44.30; H,
4.73; N, 18.79. Found: C, 44.58; H, 4.65; N, 18.55.
N3,N5-Di(ethoxycarbonyl)-2,3,5-triaminopyridine (6)
A mixture of 190 mg of 5 (0.6 mmol) in 50 mL of EtOH containing 80 mg of
5% Pd on carbon catalyst was hydrogenated in a Parrw apparatus at 40 psi H2
pressure for 4 h. The mixture was filtered through diatomaceous earth, and the
colorless filtrate was rotary evaporated, yielding 170 mg of a white solid
(100%). The crude solid was recrystallized from MeCN to give the title
compound as a white crystalline powder. Mp 166–167 8C. dH (CDCl3):
7.87 (d, J ¼ 2.2 Hz, 1H), 7.78 (s, 1H), 6.59 (s, 1H), 6.47 (s, 1H), 4.42 (bs,
NH2), 4.17 (q, J ¼ 7.2 Hz, 2H), 4.15 (q, J ¼ 6.7 Hz, 2H), 1.25
(t, J ¼ 7.1 Hz, 3H), 1.24 (t, J ¼ 7.1 Hz, 3H); dH (DMSO): 9.24 (s, 1H),
8.69 (s, 1H), 7.80 (s, 2H), 5.53 (s, 2H), 4.11 (q, J ¼ 7.1 Hz, 2H), 4.08
(q, J ¼ 7.1 Hz, 2H), 1.24 (t, J ¼ 6.9 Hz, 3H), 1.21 (t, J ¼ 6.9 Hz, 3H); dC
(DMSO): 154.22, 153.95, 148.48, 134.26, 126.01, 122.66, 118.54, 60.48,
60.06, 14.58, 14.53. Elemental analysis calculated for C11H16N4O4: C,
49.25; H, 6.01; N, 20.88. Found: C, 49.10; H, 5.97; N, 20.70.
2-Acetamido-N,N0-di(ethoxycarbonyl)-3,5-diaminopyridine (7)
A 100-mL Erlenmeyer flask was charged with 200 mg of 6 (0.7 mmol) and
20 mL of acetic anhydride. The mixture was heated to reflux, whereby all
the solids dissolved. Upon cooling to rt, the title compound crystallized as
colorless needles. The product was filtered on a coarse-porosity glass frit
and air dried (231 mg, 100%). Mp 183–185 8C. dH (DMSO): 10.23 (bs,
NH), 9.87 (s, NH), 8.68 (s, NH), 8.33 (d, J ¼ 2.3 Hz, 1H), 8.23
(d, J ¼ 2.3 Hz, 1H), 4.15 (q, J ¼ 7.2 Hz, 2H), 4.13 (q, J ¼ 7.1 Hz, 2H),
2.09 (s, 3H), 1.25 (t, J ¼ 7.2 Hz, 3H), 1.24 (t, J ¼ 7.2 Hz, 3H); dH
(DMSO): 170.33, 153.58, 153.46, 136.89, 134.29, 133.14, 128.02, 120.38,

2,3,5,6-Tetraaminopyridine Tetracarbamate
1165
98.36, 60.75, 60.57, 23.01, 14.40. Elemental analysis calculated for
C13H18N4O5: C, 50.32; H, 5.88; N, 18.06. Found: C, 50.50; H, 5.88; N, 18.06.
N,N0,N00-Tri(ethoxycarbonyl)-2,3,5-triaminopyridine (8)
A 50-mL round-bottomed flask equipped with magnetic stirbar was charged
with 10 mL of anhydrous pyridine and 2.1 g of 6 (7.8 mmol). The mixture
was stirred for 30 min to allow all the solids to dissolve. The mixture was
cooled in an ice bath, and 0.98 g of ethyl chloroformate (9 mmol, 1.15
equiv) were added dropwise over 10 min. The mixture was stirred at rt for
30 min. The mixture was poured into 150 mL of H2O and allowed to stir
overnight. The precipitate was collected on a medium-porosity glass frit and
washed with H2O. The solid was air dried on the frit (2.3 g, 86%). The
product is more than 95% by 1H NMR and can be further purified by recrys-
tallization from MeCN to give the title compound as white microcrystals. Mp
114–116 8C. dH (CDCl3): 8.39 (bs, NH), 8.30 (bs, NH), 8.19 (d, J ¼ 2.0 Hz,
1H), 8.15 (s, 1H), 7.31 (bs, NH), 4.21 (q, J ¼ 7.3 Hz, 2H), 4.19 (q, J ¼ 7.1 Hz,
2H), 4.16 (q, J ¼ 7.1 Hz, 2H), 1.27 (t, J ¼ 7.1 Hz, 3H), 1.25 (t, J ¼ 7.1 Hz,
3H), 1.24 (t, J ¼ 7.3 Hz, 3H); dC (CDCl3): 155.84, 154.48, 153.71, 137.08,
133.99, 133.68, 127.59, 122.48, 62.67, 61.84, 61.76, 14.72, 14.70, 14.60.
Elemental analysis calculated for C14H20N4O6: C, 49.41; H, 5.92; N, 16.46.
Found: C, 49.64; H, 5.98; N, 16.56.
2-Nitro-N,N0,N00-tri(ethoxycarbonyl)-3,5,6-triaminopyridine (9)
A 250-mL round-bottomed flask equipped with magnetic stirbar was charged
with 30 mL of conc. H2SO4. The acid was cooled in an ice bath before adding
3 g of 8 (8.8 mmol). The cooling bath was removed, and the solids were
allowed to dissolve at rt over 1 h. The mixture was again cooled in an ice
bath prior to and during the dropwise addition of 1.1 g of 100% HNO3
(17.6 mmol, 2 equiv). After stirring at rt for 1 h, the mixture was poured
onto 500 g of crushed ice and H2O. The pale yellow solid that precipitated
was collected on a medium-porosity glass frit and washed with H2O. The
solid was air dried on the frit for 2 h (3 g, 91%). The crude solid was recrys-
tallized from EtOH to give the title compound as fine, pale yellow needles. Mp
158–160 8C (dec.). dH (CDCl3): 9.77 (s, 1H), 9.59 (s, 1H), 8.89 (s, 1H), 7.56
(s, 1H), 4.22 (q, J ¼ 7.1 Hz, 2H), 4.20 (q, J ¼ 6.1 Hz, 2H), 4.18
(q, J ¼ 7.1 Hz, 2H), 1.27 (t, J ¼ 7.0 Hz, 3H), 1.25 (t, J ¼ 7.2 Hz, 3H), 1.22
(t, J ¼ 7.5 Hz, 3H); dC (CDCl3): 155.72, 153.46, 153.04, 135.29, 135.12,
132.69, 131.55, 122.04, 63.32, 62.67, 62.46, 14.64, 14.57, 14.50. Elemental
analysis calculated for C14H18N5O8: C, 43.64; H, 4.97; N, 18.18. Found: C,
43.75; H, 5.00; N, 18.11.

1166
M. C. Davis and D. J. Irvin
N2,N3,N5-Tri(ethoxycarbonyl)-2,3,5,6-tetraaminopyridine (10)
A mixture of 3 g of 9 (7.8 mmol), 250 mg of 5% Pd/C catalyst, and 100 mL
of anhydrous DMF was reduced on a Parrw hydrogenator for 2 h (40 psi H2).
The mixture was filtered through diatomaceous earth to remove the catalyst.
The pale pink filtrate was poured into 1 L of vigorously stirred H2O.
After several hours, the pale pink precipitate was filtered on a medium-
porosity glass frit. The crude solid was air dried on the frit (2.44 g, 88%).
A suitable solvent for recrystallization could not be found. Mp 182–
185 8C (dec.). dH (CDCl3): 9.07 (s, 1H), 8.71 (s, 1H), 8.20 (s, 1H), 7.76
(s, 1H), 5.83 (bs, 2H), 4.11 (q, J ¼ 7.1 Hz, 2H), 4.09 (q, J ¼ 6.9 Hz, 2H),
4.06 (q, J ¼ 6.9 Hz, 2H), 1.30–1.17 (m, 9H); dH (DMSO): 8.99 (s, 1H),
8.69 (s, NH), 8.15 (s, NH), 7.75 (s, NH), 5,73 (bs, NH2), 4.11
(q, J ¼ 7.1 Hz, 2H), 4.073 (q, J ¼ 7.1 Hz, 2H), 4.07 (q, J ¼ 6.9 Hz, 2H),
1.24 (t, J ¼ 7.1 Hz, 3H), 1.20 (t, J ¼ 7.1 Hz, 6H); dC (DMSO): 154.27,
154.20, 154.10, 148.71, 137.69, 129.00, 116.33, 116.28, 60.44, 60.42,
60.30, 14.46.
N,N0,N0,N000-Tetra(ethoxycarbonyl)-2,3,5,6-tetraaminopyridine (11)
A 250-mL round-bottomed flask equipped with magnetic stirbar was charged
with 50 mL of anhydrous pyridine and 2.4 g of 10 (6.9 mmol). The mixture
was stirred for 30 min to allow all the solids to dissolve. The mixture was
cooled in an ice bath, and 1.5 g of ethyl chloroformate (13.8 mmol, 2 equiv)
was added dropwise over 15 min. The mixture was stirred at rt for 1 h. The
mixture was poured into 500 mL of cold H2O and allowed to stir for 1 h.
The precipitate was collected on a medium-porosity glass frit and washed
with H2O. The solid was air dried on the frit (2.2 g, 76%). The product is
more than 95% pure by 1H NMR and can be further purified by recrystalliza-
tion from EtOH to give the title compound as soft, colorless needles. It did not
melt at temperatures less than 300 8C. dH (DMSO): 9.32 (bs, 2 NH), 8.69 (bs, 2
NH), 8.33 (s, 1H), 4.13 (q, J ¼ 7.0 Hz, 4H), 4.09 (q, J ¼ 6.6 Hz, 4H), 1.24
(t, J ¼ 7.0 Hz, 6H), 1.22 (t, J ¼ 7.0 Hz, 6H); dH (CDCl3): 8.55 (s, 1H), 8.01
(s, 2 NH), 7.46 (s, 2 NH), 4.20 (q, J ¼ 7.1 Hz, 4H), 4.16 (q, J ¼ 7.2 Hz,
4H), 1.26 (t, J ¼ 7.4 Hz, 6H), 1.25 (t, J ¼ 7.4 Hz, 6H); dC (CDCl3): 155.14,
154.39, 136.19, 130.50, 125.33, 62.83, 61.78, 14.76, 14.57. Elemental
analysis calculated for C17H25N5O8: C, 47.77; H, 5.90; N, 16.39. Found: C,
47.60; H, 5.80; N, 16.20.
ACKNOWLEDGMENT
Financial support from the Office of Naval Research is gratefully
acknowledged.

2,3,5,6-Tetraaminopyridine Tetracarbamate
REFERENCES
1167
1. National Materials Advisory Board. High-Performance Structural Fibers for
Advanced Polymer Matrix Composites; National Academies Press: Washington,
D.C., 2005.
2. Sikkema, D. J. Design synthesis properties of a novel rigid rod polymer PIPD or
‘M5’: High modulus and tenacity fibres with substantial compressive strength.
Polymer 1998, 39, 5981–5986.
3. Vogel, H.; Marvel, C. S. Polybenzimidazoles new thermally stable polyms.
J. Polym. Sci. 1961, 50, 511–539.
4. Rabilloud, G.; Sillion, B.; de Gaudemaris, G. Thermostable heterocyclic polymers
consisting of poly 2-quinoxalinones and similar cyclic compounds and their
process of manufacture. U.S. Patent 3,635,892, January 18, 1972.
5. Gerber, A. H. Thermally stable polymers derived from 2,3,5,6-tetraaminopyridine.
J. Polym. Sci., Part A: Polym. Chem. 1973, 11, 1703–1719.
6. Gerber, A. H. Preparation of heterocyclic polymers from heteroaromatic tetraa-
mines. U.S. Patent 3,804,804, April 16, 1974.
7. Gerber, A. H. Substituted tetraamino heterocyclic compounds, useful in the prep-
aration of substituted polybenzimidazoles and poly-imidazopyrrolones. U.S.
Patent 3,943,125, March 9, 1976.
8. Arnold, F. E. Preparation of polybenzimidazoles. U.S. Patent 4,002,679, January
11, 1977.
9. Gerber, A. H. Polyheterocyclic polymers derived from substituted tetraamino
pyridines. U.S. Patent 4,079,039, March 14, 1978.
10. Williams, R. L.; Cohen, S. A. The chemistry of aryltetraamines, II: The synthesis
of 2,3,4,5-tetraaminopyridine. J. Heterocycl. Chem. 1971, 8, 841–843.
11. Sikkema, D. J. Nitration of pyridine-2,6-diamine. U.S. Patent 5,945,537, August
31, 1999.
12. Gerber, A. H. Acid addition salts of 2,3,5,6-tetraaminopyridine and a process for
their preparation. U.S. Patent 3,740,410, June 19, 1973.
13. Hollins, R. A.; Merwin, L. H.; Nissan, R. A.; Wilson, W. S.; Gilardi, R. Aminoni-
tropyridines and their N-oxides. J. Heterocycl. Chem. 1996, 33, 895–904.
14. Maier-Bode, H. Darstellung von 3-amino-pyridin und 3.5-diamino-pyridin. Chem.
Ber. 1936, 69, 1534–1537.
0
¨
¨
15. Meyer, H.; Tropsch, H. Uber dinicotinsaure und deren abbau zu bb -diaminopyr-
idin und u¨ber das aa0-diaminopyridin: Vierte mitteilung u¨ber diamine der pyridin-
reihe. Monatsh. Chem. 1914, 35, 207–217.
16. Clark-Lewis, J. W.; Thompson, M. J. Methylation of 3-aminopyridines and prep-
aration of 2-amino-3-methylaminopyridine and 2:3-diaminopyridine. J. Chem.
Soc. 1957, 442–446.
17. Johnson, C. D.; Katritzky, A. R.; Viney, M. Mechansim of the electrophilic substi-
tution of heteroaromatic compounds, VII: Nitration of pyridines in the a-position
and rules for the nitration of substituted pyridines. J. Chem. Soc. B 1967, 11,
1211–1213.
¨
¨
18. Koenigs, E.; Gerdes, H. C.; Sirot, A. Uber die nitrierung des 3-athoxy-pyridins.
Chem. Ber. 1928, 61, 1022–1030.
19. Katritzky, A. R. The preparation and properties of pyridino(10:20-2:3)-1-oxa-2:4-
diazol-5-one. J. Chem. Soc. 1956, 2063–2066.
20. Kurita, K.; Williams, R. L. Heterocyclic studies: Aryltetraamines, III:
The chemistry of 2,3,5,6-tetraaminopyridine. J. Heterocycl. Chem. 1975, 12,
789–791.