Synthesis of trinitroaromatics using alternative mixed acid nitration conditions

Article abstract of DOI:10.1080/00397911.2010.481743

Conditions for the mild and efficient nitration of phloroglucinol (1,3,5-trihydroxybenzene), 5-methoxyresorcinol, 3,5-dimethoxyphenol, and 1,3,5-trimethoxybenzene have been developed. Yields of the trinitro derivatives are excellent (～90%) for systems hav

Full text of DOI:10.1080/00397911.2010.481743

Synthetic Communications1, 40: 2513–2519, 2010
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2010.481743
SYNTHESIS OF TRINITROAROMATICS USING
ALTERNATIVE MIXED ACID NITRATION CONDITIONS
Nicholas A. Straessler
Research and Development, ATK Space Systems, Brigham City, Utah, USA
Conditions for the mild and efficient nitration of phloroglucinol (1,3,5-trihydroxybenzene),
5-methoxyresorcinol, 3,5-dimethoxyphenol, and 1,3,5-trimethoxybenzene have been developed.
Yields of the trinitro derivatives are excellent (ꢀ90%) for systems having one or more
hydroxyl groups, and in the case of 1,3,5-trimethoxybenzene, the trinitro analog was obtained
in 62% yield. The optimum nitration conditions utilize sulfuric acid (94–98%) and an inorganic
nitrate salt.
Keywords: Dimethoxypicric acid; methoxystyphnic acid; nitration; trimethoxy-trinitrobenzene;
trinitrophloroglucinol
INTRODUCTION
A fundamental challenge in preparing highly nitrated aromatic species is
overcoming the inherent ring deactivation caused by incorporation of two or more
nitro groups. Thus, although mono- and dinitrations of aromatics are generally
facile, trinitrations are comparatively more difficult. Trinitrations typically necessi-
tate more vigorous reaction conditions than mono- or dinitrations and as a result
promote oxidative decomposition of starting materials, intermediates, and products
that lead to poor chemical yields.[1,2a–c] A number of nitration strategies have been
reported,[3,4] but few have been exploited to efficiently trinitrate aromatics.
Sulfuric acid solutions of nitrate salts (NaNO3, KNO3) were once widely
used as nitrating agents but eventually lost popularity in favor of mixed acids as
nitric acid became more readily available.[5a] Examples of nitroaromatics synthesized
from sulfuric acid or oleum solutions of potassium nitrate include dinitroquinoline,[6]
1,3,5-tribromo-2,4,6-trinitrobenzene,[7] 1,3,5-trichloro-2,4,6-trinitrobenzene,[7] 1,5-
dibromo-2,4-dinitrobenzene,[8] and 1,3-dibromo-2,4,6-trinitrobenzene.[8] More
recently, Lu and coworkers reported the preparation of 2,4,6,8,10,12-hexanitro-
2,4,6,8,10,12-hexaazaisowurtzitane (CL-20) using superacid solutions of potassium,
sodium, or ammonium nitrate.[9] Kinetic studies have also been conducted on
nitrations of anthraquinone with nitrate salts of various cations in sulfuric acid.[10]
Received July 24, 2009.
Address correspondence to Nicholas A. Straessler, Research and Development, ATK Space
Systems, Brigham City, UT 84302-0707, USA. E-mail: Nick.Straessler@ATK.com
2513

2514
N. A. STRAESSLER
Polynitroaromatic compounds are renowned for their utility in the field of
energetic materials.[1,5a,5b] Nitrated phenols and phenolic ethers are of particular
interest because they serve as synthetic intermediates to a diverse range of
explosives.[1,5,11–14] Phloroglucinol (PG) has been converted to trinitrophloroglucinol
(1) by mixed acid nitration,[15,16] nitration with N2O5 in sulfuric acid,[12] oxidation of
the trinitroso intermediate,[17] and nitration of the corresponding triacetate followed
by –OH restoration via hydrolysis.[12] To the best of our knowledge, 3-methoxys-
typhnic acid (2) has not been reported, but its parent compound, styphnic acid,
prepared by sulfonation and ensuing nitration of resorcinol, is well known.[5a]
Tribromotrinitrobenzene[18] and pentanitrophenol[19,20] have both been converted
to 3,5-dimethoxypicric (DMP) acid (3) by treatment with sodium methoxide.
Nitration of 1,3,5-trimethoxybenzene (TMB) has been thoroughly investigated by
Bellamy and coworkers, who obtained moderate yields of 1,3,5-trimethoxy-2,4,6-
trinitrobenzene (4) using N2O5 in acetonitrile with sulfuric acid as a catalyst.[21]
Herein, we present a means of synthesizing four trinitroaromatic compounds
in moderate to excellent yields employing a mild nitration mixture of sþulfurþic acid
(94–98%) and an inorganic nitrate salt, XNO3, where X ¼ NHþ4 , Na , K . The
aromatic starting materials are PG, 5-methoxyresorcinol (MR), DMP, and TMB.
RESULTS AND DISCUSSION
The combination of a nitrate salt in sulfuric acid is derived from the common
mixed acid nitrating reagent. However, the additional equilibrium between the
nitrate anion and nitric acid distinguishes this reagent from mixed acid (Eq. 1).
Hþ
Hþ
NO3ꢁ Ð HNO3 Ð NO2þ þ H2O
ð1Þ
ꢁHþ
ꢁHþ
The initial equilibrium is assumed to mediate the nitration reaction by controlling
the amount of nitric acid and subsequent nitronium ions available for nucleophilic
attack by the aromatic substrate.
The nitrate salt in sulfuric acid has several advantages over mixed acid
nitrations: (1) nitrate salts are more economical, have a longer shelf life, and are less
hazardous than nitric acid; (2) a minimal temperature increase is observed upon
mixing nitrate salts with sulfuric acid compared to the considerable exotherm
encountered when adding nitric acid to sulfuric acid; (3) heating nitrate salt = sulfuric
acid reactions does not generate visible NOx gases; and (4) sulfuric acid is partially
neutralized with the nitrate salt as the reaction proceeds, aiding in the disposal of
spent acid. Furthermore, the in situ generation of nitric acid limits the amount of
oxidant available in solution to compete with the nitration reaction.
We evaluated the efficacy of the three nitrate salts individually dissolved in
sulfuric acid (94–98%) as nitrating agents for the four aromatic starting materials.
The choice of nitrate salt had little observed effect on chemical yield and purity of
1 and 2. PG and MR were both converted to their trinitro counterparts in compa-
rable yields and purities with all three nitrate salts in 10 min. Ultimately, ammonium
nitrate was the preferred salt because of its rapid dissolution in sulfuric acid and
consistently excellent yields of 1 (91% yield) and 2 (96% yield) (Scheme 1).

SYNTHESIS OF TRINITROAROMATICS
2515
Scheme 1. Preparation of 1 (top) and 2 (bottom).
The identity of the starting nitrate salt had a more pronounced effect on the
nitrations of DMP and TMB. DMP was most favorably converted to 3 (85% yield)
in 20 min using sodium nitrate (Scheme 2). When potassium nitrate was used,
reactions took approximately 15 min and afforded 3 in good yield and purity.
Ammonium nitrate successfully converted DMP to 3 in only 10 min, but the reac-
tions frequently yielded a crude product that was tan or brown in color, although
nearly identical by NMR spectroscopy to the yellow material recovered from the
sodium and potassium nitrate reactions.
The best conditions for the synthesis of 4 (62% yield) from TMB included 3
molar equivalents of potassium nitrate with heating to 50 ꢂC (Scheme 3). Three
molar equivalents of ammonium nitrate at 45 ꢂC also produced good-quality 4,
but yields were slightly better with potassium nitrate. Four molar equivalents of
sodium nitrate were necessary to obtain similar results at 40 ꢂC for 30 min. Heating
to 65 ꢂC with 3 molar equivalents of sodium nitrate gave a 52% yield of 4. A
summary of observed nitration results for all four starting materials is shown in
Table 1.
Mixtures of ice and water were used to quench the nitration reactions, and the
amounts of each played an important role in yield and product appearance. Com-
pounds 1, 2, and 3 are water soluble so the sulfuric acid reaction solvent was used
Scheme 2. Preparation of 3.

2516
N. A. STRAESSLER
Scheme 3. Preparation of 4.
Table 1. Summary of nitration results
XNO3 (Xþ)
Reaction timec (min)
Yield (%)
a
Reaction
PG ! 1
NH4
K
10
10
91
89
88
96
90
90
80
83
85
61
62
52
60
Na
NH4
K
10
10
MR ! 2
10
Na
NH4
K
10
10
DMP ! 3
TMB ! 4
15
Na
NH4
K
20
heated to 40 ꢂC
heated to 50 ꢂC
heated to 65 ꢂC
30 @ 40 ꢂC
Na
Nab
a3 mol. equivalents based on starting aromatic unless noted otherwise.
b4 mol. equivalents based on TMB.
cFor TMB!4, ramp rates are ꢀ5 ꢂC=min. Reactions quenched at indicated
temperature.
to keep the pH low enough to promote precipitation upon quenching. A point of
diminishing returns was reached if too much ice or water was used (>5.75 mM 1
in H2O, >60 mM 2 and 3 in H2O) to recover 1, 2, and 3 as significant portions of
product would remain dissolved. Compound 4 is insoluble in water, so the volume
used for quenching the reactions was less influential and not investigated further.
Compounds 1 and 2 precipitated out of solution as the nitration reaction proceeded
but were still added to ice to aid in product filtration and isolation. Compound 3 was
most sensitive to the amount of ice and water used for product recovery. It was
determined that 75 g of ice mixed with 75 g of water was ideal for quenching the
reactions starting with 250 mg of DMP. Lesser amounts of ice=water tended to
produce tan- or brown-colored product as opposed to yellow, although the NMR
spectra did not always reflect appreciable purity differences in such cases. The
variations in product color were more apparent when ammonium nitrate was used
as the nitro source instead of sodium or potassium nitrates, particularly in the
synthesis of 3. Moderate success at purifying brown-colored product was achieved
by flash chromatography with ethyl acetate and silica gel.

SYNTHESIS OF TRINITROAROMATICS
2517
CONCLUSION
The straightforward synthesis of a series of four trinitrophenol=ether
derivatives employing a stoichiometric amount of ammonium, potassium, or sodium
nitrate in sulfuric acid has been described. The choice of the nitrate salt had minimal
effects on the nitrations of aromatics with two or three hydroxyl groups but had a
marked impact on the nitrations of aromatics with one or no hydroxyl groups. This
nitration strategy displays clear advantages over the more popular mixed acid
nitration approach.
EXPERIMENTAL
General
Warning: Nitrated aromatics, including those described here, are potentially
explosive. Extreme caution should be exercised when handling these compounds.
Minimize exposure of these materials to impact, friction, heat, and electrostatic
discharge.
Sulfuric acid (94–98%) was purchased from VWR International. Phlorogluci-
nol dihydrate, 5-methoxyresorcinol, 3,5-dimethoxyphenol, 1,3,5-trinitrobenzene,
ammonium nitrate, sodium nitrate, and potassium nitrate were purchased from
Aldrich Chemical Company and used as received. CD2Cl2 and CDCl3 were obtained
from Cambridge Isotopes Laboratories. Water was purified in-house using a typical
double-distillation apparatus. 1H and 13C NMR data were collected on a Jeol Eclipse
þ400-MHz spectrometer; the chemical shifts are reported in d (ppm) relative to
1
1
residual solvent peaks (CDCl3 d H 7.25, 13C 77.00; CD2Cl2 d H 5.31, 13C 53.08).
Melting points are uncorrected and were determined using the standard open
capillary method. Elemental analyses were performed on a Perkin-Elmer model
2400 series II CHNS=O analyzer.
Synthesis and Characterization
2,4,6-Trinitrophloroglucinol monohydrate (1). A round-bottom flask was
charged with sulfuric acid (94–98%, 30 mL) and chilled to approximately 5 ꢂC.
Ammonium nitrate (1.48 g, 18.48 mmol) was added with stirring at a rate such that
the temperature did not exceed 10 ꢂC. Once the solution temperature returned to
5 ꢂC, phloroglucinol dihydrate (PGDH; 1.00 g, 6.16 mmol) was added at a rate such
that the temperature did not exceed 10 ꢂC. Vigorous stirring was maintained to
visibly prevent concentrating the solid in the center vortex. After PGDH addition
was complete and the associated exotherm began to subside, the cooling bath was
removed and the reaction was stirred for an additional 10 min. The heterogeneous
yellow mixture was added in one portion to crushed ice (100 g) and was stirred gently
until all the ice had melted. The precipitate was isolated by vacuum filtration, washed
with cold 10% HCl, and air dried to afford 2,4,6-trinitrophloroglucinol monohydrate
(1.57 g, 91%) as a yellow solid. Melting point and 1H and 13C NMR spectra matched
those previously reported.[11]

2518
N. A. STRAESSLER
5-Methoxystyphnic acid (2). Similar to 1, ammonium nitrate (1.72g,
21.48 mmol) and MR (1.00 g, 7.14mmol) were used in the reaction. The precipitate
was isolated by vacuum filtration, washed with cold 10% HCl, and air dried to afford
5-methoxystyphnic acid (1.89g, 96%) as a light yellow solid, mp¼ 165–167ꢂC
1
(decomp.): H NMR (CD2Cl2) d 4.09 (s, 3H, CH3), 11.37 (s, 2H, OH); 13C NMR
(CD2Cl2) d 61.99, 118.34, 126.20, 151.22, 152.02. Elemental analysis calculated for
C7H5N3O9: C, 30.56; H, 1.83; N, 15.27. Found: C, 30.12; H, 1.54; N, 14.83.
3,5-Dimethoxypicric acid (3). A round-bottom flask was charged with sulfu-
ric acid (94–98%, 10 mL) and chilled to approximately 5 ꢂC. Sodium nitrate (410 mg,
4.82 mmol) was added with stirring at a rate such that the temperature did not exceed
10 ꢂC. Once the solution temperature returned to 5 ꢂC, DMP (250 mg, 1.62 mmol) was
added at a rate such that the temperature did not exceed 10 ꢂC. Vigorous stirring was
maintained to visibly prevent concentrating the solid in the center vortex. After DMP
addition was complete and the associated exotherm began to subside, the cooling
bath was removed and the reaction was stirred for an additional 20 min. The dark
red solution was added in one portion to a mixture of ice (75 g) and water (75 g)
and was stirred gently until all the ice had melted. The precipitate was isolated by
vacuum filtration, washed with cold 10% HCl, and air dried to afford 3,5-dimethoxy-
picric acid (400 mg, 85%) as a light yellow solid, mp ¼ 75–76 ꢂC: 1H NMR (CDCl3) d
4.05 (s, 6H, CH3), 11.25 (br s, OH); 13C NMR (CDCl3) d 63.83, 127.53, 133.47,
150.57, 150.79. Elemental analysis calculated for C8H7N3O9: C, 33.23; H, 2.44; N,
14.53. Found: C, 33.25; H, 2.17; N, 14.37.
1,3,5-Trimethoxy-2,4,6-trinitrobenzene (4). A round-bottom flask was
charged with sulfuric acid (94–98%, 10 mL) and chilled to approximately 5 ꢂC in
an ice bath. Potassium nitrate (452 mg, 4.47 mmol) was added with stirring at a rate
such that the temperature did not exceed 10 ꢂC. After addition was complete and the
temperature returned to 5 ꢂC, TMB (250 mg, 1.49 mmol) was added at a rate such
that the temperature did not exceed 10 ꢂC. Vigorous stirring was maintained to visi-
bly prevent concentrating the solid in the center vortex. After TMB addition was
complete and the associated exotherm began to subside, the reaction was warmed
(5 ꢂC=min) to 50 ꢂC. The dark red solution was added in one portion to crushed
ice (60 g) and stirred gently until all the ice had melted. The precipitate was isolated
by vacuum filtration, washed with distilled water, and air dried to yield 1,3,5-
trimethoxy-2,4,6-trinitrobenzene (280 mg, 62%) as a light yellow solid. Melting point
1
and H and 13C NMR spectra matched those previously reported.[21]
ACKNOWLEDGMENTS
This research was supported by the Department of Defense: Strategic Environ-
mental Research and Development Program (SERDP Project WP 1582) and per-
formed under ATK Space Systems Contract W912HQ-07-C-0018. Max Patterson
of ATK Space Systems is gratefully acknowledged for his support with the NMR
spectrometer, and Kieth Nielsen of ATK Space Systems is gratefully acknowledged
for performing the elemental analyses. Thanks to Wayne Edwards and Clint Nelson
for technical assistance with this work.

SYNTHESIS OF TRINITROAROMATICS
2519
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