Synthesis and Characterization of the Potential Melt-Castable Explosive 3-(1,2,4-Oxadiazolyl)-5-Nitratomethyl Isoxazole

Article abstract of DOI:10.1002/cplu.202100175

The synthesis of 3-(1,2,4-oxadiazolyl)-5-nitratomethyl isoxazole (C₆H₄N₄O₅), its physical properties, and its theoretical performances are described. This energetic material was found to have a melting point range of 76.6–79.2 °C, and a thermal onset decomposition temperature of 184.5 °C. These thermal features put this material into the standalone melt-castable explosive class. The material was found to have TNT performance, and was found to be insensitive to impact, friction, and electrostatic discharge, despite having a nitric ester functionality. A critical reaction in making this molecule was the desymmetrization of diaminoglyoxime. The optimization of this transformation is described. Previous reports of this desymmetrization were found to be inaccurate, as the desymmetrization reaction produces a co-crystal of mono- and bi-1,2,4-oxadiazole products.

Full text of DOI:10.1002/cplu.202100175

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Synthesis and Characterization of the Potential Melt-
Castable Explosive 3-(1,2,4-Oxadiazolyl)-5-Nitratomethyl
Isoxazole
Eric C. Johnson,[a] Tristen A. Reid,[a] Christopher W. Miller,[a] Jesse J. Sabatini,*[a]
Rosario C. Sausa,[b] Edward F. C. Byrd,[b] and Joshua A. Orlicki[c]
having the highest densities and therefore, the best
performances.[3]
The synthesis of 3-(1,2,4-oxadiazolyl)-5-nitratomethyl isoxazole
(C6H4N4O5), its physical properties, and its theoretical perform-
ances are described. This energetic material was found to have
Yet many highly symmetrical and rigid molecules are also
typically associated with materials that have high melting
points. While materials that have excessively high melting
points are satisfactory for pressable secondary explosives, high
melting points tend to be frowned upon for materials that are
°
a melting point range of 76.6–79.2 C, and a thermal onset
°
decomposition temperature of 184.5 C. These thermal features
put this material into the standalone melt-castable explosive
class. The material was found to have TNT performance, and
was found to be insensitive to impact, friction, and electrostatic
discharge, despite having a nitric ester functionality. A critical
reaction in making this molecule was the desymmetrization of
diaminoglyoxime. The optimization of this transformation is
described. Previous reports of this desymmetrization were
found to be inaccurate, as the desymmetrization reaction
produces a co-crystal of mono- and bi-1,2,4-oxadiazole prod-
ucts.
to be used as standalone melt-castable explosives. Temper-
[2a]
°
atures of 70–95 C are ideal for melt-castable materials, since
materials in this range can be melted with steam. Materials that
exhibit melting points >95–125 C can still be classified as
melt-castable materials, but are typically combined with other
materials to form a eutectic and depress the melting point, in
°
°
hopes of bringing it down to the 70–95 C range.
While symmetrical bis-nitratomethyl-bis-isoxazole[2b] was re-
cently been found to serve as a potential melt-castable
explosive, it was believed that the floppiness of the
nitratomethyl moiety assisted in lowering the melting point by
lowering the overall rigidity of the molecule. With this
information in hand, it was felt that developing a non-
symmetrical isoxazole/1,2,4-oxadiazole hybrid energetic materi-
al containing the nitratomethyl functionality would also lead to
materials containing some interesting properties (Figure 1).
In synthesizing 2, we first needed to desymmetrize
The development of high-energy-density materials (HEDMs)[1]
with high performance and reasonable sensitivity is an over-
arching goal in the field of energetic materials. A main thrust of
our ongoing research efforts lies in the areas of melt-castable
explosives, and we have discussed the characteristics that make
a good melt-cast explosive in previous publications.[2] For CHNO
materials, density is critical in maximizing performance, and a
common way to maximize density is to incorporate high heat
of formation-based heterocycles into a rigid structure with little
floppiness that can then be nitrated to further increase the
oxygen balance of a molecule. Such rigid energetic molecules
with a high degree of symmetry are usually associated with
diaminoglyoxime (DAG).[4] DAG, in the presence of 1.50 eq. of
.
°
triethyl orthoformate and catalytic BF3 Et2O heated to 75–80 C
for 10 min was reported by Andrianov et al. to proceed in 80%
yield after filtration and recrystallization from hot water to give
mono 1,2,4-oxadiazole 3.[5] However, when we attempted to
reproduce this reaction, it led to only a 33% yield of monocyclic
product 3 being obtained. Under the conditions detailed by
Andrianov et al., significant amounts of bis-1,2,4-oxadiazole 4
(55%) were obtained (Scheme 1).
[a] E. C. Johnson, T. A. Reid, C. W. Miller, Dr. J. J. Sabatini
CCDC US Army Research Laboratory
Energetics Synthesis & Formulation Branch
Aberdeen Proving Ground,
In our hands, we found that 1.30 eq. of triethyl orthoformate
was the optimal amount in order for good yields of 3 to be
°
obtained. After stirring this reaction for 1 h at 75 C in the
presence of catalytic BF3 Et2O, the reaction mixture was first
MD 21005 (USA)
.
E-mail: jesse.j.sabatini.civ@mail.mil
[b] Dr. R. C. Sausa, Dr. E. F. C. Byrd
CCDC US Army Research Laboratory
Detonation Sciences & Modeling Branch
Aberdeen Proving Ground,
°
cooled to ambient temperature and then further to 0 C. The
voluminous solid that appeared was filtered. At this stage, the
MD 21005 (USA)
[c] Dr. J. A. Orlicki
CCDC US Army Research Laboratory
Polymers Branch
Aberdeen Proving Ground,
MD 21005 (USA)
Figure 1. Molecular structures of synthesized energetic dinitrate 1 and
proposed mononitrate 2.
Supporting information for this article is available on the WWW under
https://doi.org/10.1002/cplu.202100175
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Table 1. Physical and explosive properties of nitric ester 2 as compared to
TNT and dinitrate 2.
Data category
TNT[5]
1
2
[a]
°
Tm [ C]
80.4
295
92.0
76.6
[b]
°
Tdec [ C]
189.2
À 61.5
À 16.8
1.61
184.5
À 67.9
À 22.6
1.641
21.0
7087
À 5.8
>15
ΩCO2 [%][c]
À 74
ΩCO [%][d]
À 24.7
1 [gcmÀ 3
]
1.65
[e]
Pcj [GPa][f]
Vdet [msÀ 1
°
20.5
19.3
[g]
]
6950
À 59.3
15
>360
>0.25
7060
À 139
11.2
>360
0.25
À 1 [h]
ΔfH [kJmol
]
IS[i] [J]
FS[j] [N]
>360
>0.20
ESD[k] [J]
Scheme 1. Synthesis of mononitric ester 2.
[a] Tm =onset temperature of melting; [b] Tdec =onset temperature of
decomposition; [c] ΩCO2=CO2 oxygen balance; [d] ΩCO =CO oxygen
balance; [e] 1=experimentally determined density. TNT was determined
by gas pycnometry. 1 and 2 were determined by single crystal x-ray
crystallography; [f] Pcj=detonation pressure; [g] Vdet =detonation velocity;
solid product obtained was determined to be a co-crystal of 3
°
and 4. Heating this co-crystal in a beaker of water to 50 C to
°
[h] ΔfH =molar enthalpy of formation; [i] IS=impact sensitivity; [j]
FS=friction sensitivity; [k] ESD=electrostatic discharge sensitivity.
dissolve the solid, and then letting it cool to ambient temper-
ature set the stage for a second filtration. This time, however, it
was discovered that the bulk of 4 was retained on the filter,
while the bulk of 3, contaminated with a small amount of 4,
was present in the mother liquor. Ultimately, it was found that
this second filtration was not needed. Treatment of the co-
crystal of 3/4 to conditions with sodium nitrite and concen-
trated HCl afforded hydroximoyl chloride 5, isolated as a white
solid of high purity that matched the characterization data
outlined by Andrianov et al.[5] Treatment of 5 with propargyl
alcohol in a [3+2] cycloaddition reaction yielded hydroxymeth-
yl isoxazole 6, which was purified by triturating the crude solid
in diethyl ether. Nitration of 6 with 98% HNO3 proceeded
uneventfully and in high yield to give nitric esters 2. Overall, 2
was synthesized from glyoxal in a 10 gram quantity in 5 steps,
and in 16% overall yield.
ester functionality, 2 was found to possess a lower sensitivity to
impact and friction compared to TNT.
Single crystal x-ray diffractometry helped identify unequiv-
ocally the molecular conformation of 2, as well as reveal its key
intermolecular interactions. The Supporting Information pro-
vides details on the data acquisition, structure solution, and
structure refinement.[6] A crystallographic analysis of 2 (Deposi-
tion Number 2077647) reveals one molecule in the asymmetric
unit (Figure 3a). The molecule consists of an oxadiazole ring
[r.m.s. deviation=0.002 Å], an isoxazole ring [r.m.s. deviation=
0.002 Å], and a near planar alkyl nitric ester group [C6/O3/N4/
O4/O5; r.m.s. deviation=0.019 (1) Å] bonded to the isoxazole
ring. The 10 C, N, and O ring- atoms adopt a near planar
geometry [r.m.s. deviation=0.037 (2) Å] with a maximum out-
of-plane deviation of 0.037 (2) Å for the N3 atom, and the
As shown by the DSC trace in Figure 2, 2 was found to have
a lower melting point compared to the bis-isoxazole dinitrate
1,[2b] and exhibited a melting point close to TNT. In fact, 2 was
found to have very similar properties to TNT with respect to
density, detonation pressure and detonation velocity (Table 1).
Despite the presence of the widely perceived sensitive nitric
°
isoxazole ring subtends a dihedral angle of 59.3 (2) with
respect to the alkyl nitric ester plane. The molecule’s bond
length and angles are in the usual range, consistent with those
reported for other isoxazoles, oxadiazoles and their
derivatives.[2c,7]
Intermolecular interactions play a key role in the crystal
8]
packing of 2.[7,
The interatomic contact distances range
between 2.574 (3) and 3.236 (3) Å with the N···H and O···H
dominating the van der Waals intermolecular interactions.
Specifically, 2 presents short contacts between atoms N3 and
atoms H6 A of adjacent molecules and atoms N1 and atoms H4
of adjacent molecules [N3···H6Ai =2.547 (4) Å; N1···H4i =2.574
(4) Å; symmetry code (i): (x, À 1+y, z)]. Also, atoms O2 are in
close proximity to atoms H6 A of nearby molecules [O2···H6Aii =
2.659 (3) Å; symmetry code (ii): (À x, À 1+y, z)], as are the H1
atoms of the oxadiazole ring with O3 atoms of nearby
molecules [H1···O3Aii =2.635 (3) Å; symmetry code (ii): (1x, À y,
1-z)]. The contact distances between the atoms C2 and N3 of
adjacent molecules measure 3.236 (3) Å [C2···N3iii =3.236 (3) Å;
symmetry code (iii): (À x, À 1+y, z)]. Figure 3b shows the crystal
stacking of 2 along the a-axis. The molecule’s 10-atom ring
planes are nearly parallel to the b-axis and stack in the vicinity
Figure 2. DSC trace of nitric ester 2.
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supplementary crystallographic data for this paper. These data are
provided free of charge by the joint Cambridge Crystallographic
Data Centre and Fachinformationszentrum Karlsruhe Access Struc-
tures service www.ccdc.cam.ac.uk/structures. Caution! Although we
did not experience any problems handling the compounds described
in this paper, when handling energetic materials such as 2, proper
laboratory precautions should be taken. Laboratories and personnel
should be properly grounded, and safety equipment such as heavy
Kevlar/steel gloves, reinforced Kevlar coat, ballistic face shield, ear
plugs, and blast shields are necessary.
3-(1,2,4-oxadiazolyl)-hydroximoyl chloride (5): To 1 1 L round-
bottom flask equipped with a stir bar was added diaminoglyoxime
(118 g, 1.00 mol, 1 eq), 221 mL of 98% triethyl orthoformate
(196.5 g, 1.30 mol, 1.30 eq), and 12.3 mL of BF3 diethyl etherate
(14.2 g, 0.100 mol, 0.100 eq) . The reaction mixture was immersed
°
in an oil bath, heated to 75–80 C, and stirred for 1 h. The reaction
°
mixture was first cooled to ambient temperature, and then to 0 C
by immersing the round-bottom flask into an ice bath. The resulting
solid was collected by Büchner filtration, rinsing the flask with a
minimal amount of cold triethyl orthoformate. The solids were
transferred to a crystallization dish, and was dried overnight in a
fume hood to afford 128 g of a white solid. This solid contains a
mixture of monocyclized- and dicyclized-1,2,4-oxadiazole products.
128 g of this white solid and a stir bar was added to a 2 L-three-
neck-round-bottom flask, and 700 mL of concentrated HCl was
added. The reaction mixture was immersed into an ice-water bath,
Figure 3. a) Molecular configuration and atom-numbering scheme for 2.
Non-hydrogen atoms are shown as 50% probability displacement ellipsoids;
b) Crystal packing for 2 along the a-axis direction; Atoms C, H, O, and N are
shown in grey, white, blue, and red, respectively. Blue and red dashed lines
depict N···H and O···H intermolecular contacts.
°
and was chilled to 0–5 C. 700 mL of distilled water was added, and
the reaction mixture was stirred for 30 minutes until a temperature
°
of 0–5 C was reached. 104 g of NaNO2 was dissolved in 250 mL,
and was added over 4 hours via a 500 mL addition funnel. During
this addition, the temperature was monitored and was not allowed
°
to rise above 10 C. After the addition was complete, the reaction
mixture was stirred overnight for 16 h, during with time the ice-
°
of the b-axis. Crystal 2 contains four S1 molecules in its unit cell
and belongs to the monoclinic system, P21/n space group.
Based on its molecular mass and lattice constants of a=
water bath melted, and the temperature rose to 20 C. The reaction
°
mixture was re-cooled to 0 C by means of an ice-water bath, the
solids were collected by Büchner filtration, and the solid was
washed with distilled water (3×500 mL). The solid was transferred
to a crystallization dish, and was dried overnight in a fume hood to
afford 51.6 grams (35% from DAG) of hydroximoyl chloride 5 as a
white solid. 5 matched the analytical characteristics as described by
Andrianov et al.[5]
°
6.4077(8) Å, b=5.7834 (6) Å, c=23.183 (2) Å, α=γ=90 , and
°
β=91.724 (8) , we obtain a density of 1.641 g/cc at 298 K.
In summary, heterocyclic nitric ester 2 was synthesized in a
5 step, 16% overall yielding process from glyoxal. A key to the
synthesis was the desymmetrization of diaminoglyoxime (DAG)
to yield mono-1,2,4-oxadiazole 3. Interestingly, conversion of 3
to hydroximoyl chloride 5 via the Sandmeyer reaction was
found to yield the desired product in a clean fashion by means
of filtration. 2 was found to exhibit standalone melt-castable
properties, with a similar density, melting point, detonation
velocity, and detonation pressure as compared to TNT.
3-(1,2,4-oxadiazolyl)-5-(hydroxymethyl)-isoxazole (6): To
a 2 L
round-bottom flask equipped with a stir bar were sequentially
added 1 L of EtOH, 48.9 mL of propargyl alcohol (47.5 g, 0.850 mol,
5.00 equiv), and NaHCO3 (42.8 g, 0.509 mol, 3.00 equiv). The reac-
°
tion mixture was cooled to 0 C, and the flask was fitted with a
pressure-equalizing liquid addition funnel. 5 (25.0 g, 0.170 mol,
1.00 equiv) was dissolved in 300 mL of EtOH, and was added
dropwise over 6 h, during which time the temperature was not
°
allowed to rise above 10 C. After the addition was complete, the
ice bath was removed, and the reaction mixture was stirred
overnight at ambient temperature. The reaction mixture was
filtered and the solid was discarded. The mother liquor was
transferred to a 2 L round-bottom flask and was concentrated in
vacuo to afford a crude dark brown solid. The crude solid was
triturated with 200 mL of Et2O for 4 h. The solid was collected by
Büchner filtration and was dried under suction overnight to afford
20.39 g (72%) of isoxazole 6 as a light brown powder. Tmelt (onset)=
Experimental Section
General Methods: Chemicals and solvents were used as received
1
from Sigma-Aldrich. H and 13C NMR spectra were recorded using a
Bruker 400 MHz instrument. The chemical shifts quoted in parts per
million in the text refer to typical standard tetramethyl silane in
CDCl3 as the solvent. Infrared spectra were measured with a Bruker
Alpha-P FTIR instrument. Melting and decomposition temperatures
°
°
°
°
115.8 C; Tmelt (peak)=120.6 Tdec =172.9 C (onset), 207.2 C (peak);
1H NMR (400 MHz, DMSO-d6) δ 9.88 (s, 1H), 6.93 (s, 1H), 5.81 (s, 1H),
4.68 (s, 2H); 13C NMR (100 MHz, DMSO-d6) δ 175.3, 168.4, 160.1,
151.9, 101.3, 54.6; IR (neat) cmÀ 1 3370 (m), 3113 (m), 1569 (s), 1528
(s).
were measured at
a heating rate of 10 C/min using a TA
Instruments Q10 DSC instrument in aluminium pans containing a
pinhole. Single-crystal X-ray diffraction studies were performed
with a SuperNova Dualflex diffractometer containing an EosS2
charge-coupled device detector and a Mo Kα radiation source (λ=
0.71073 Å).[7] Deposition Number 2077647 for 2 contains the
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[1] T. M. Klapötke, Chemistry of High-Energy Materials, 3rd ed.; De Gruyter,
Berlin, 2015.
3-(1,2,4-oxadiazolyl)-5-(nitratomethyl)-isoxazole (2): To a 100 mL
round-bottom flask immersed in an ice bath was added 30 mL of
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°
98% HNO3. After the nitric acid was chilled to 0 C, alcohol 2
(10.0 g, 59.9 mmol, 1.00 equiv) was added in four equal portions
°
over 1 h, during which time the temperature did not exceed 10 C.
After the addition was complete, the reaction mixture was stirred
for 4 h, during which time the ice bath was allowed to melt, and
the reaction mixture was allowed to warm to ambient temperature.
The reaction mixture was poured onto crushed ice with stirring.
After 3 h, the solid was collected by Büchner filtration and was air-
dried in a well-ventilated fume hood to afford nitrate 2 as a crude
light yellow solid. Crude
2 was recrystallized from boiling
isopropanol to afford 10.3 g (81%) of the pure product as a white
°
°
°
solid. Tmelt (onset)=76.6 C; Tmelt (peak)=79.2 C
T
dec =184.5 C
(onset), 209.7 C (peak); 1H NMR (400 MHz, Acetone-d6) δ 9.57 (s,
1H), 7.25 (s, 1 H), 5.94 (s, 2H), 13C NMR (100 MHz, Acetone-d6) δ
168.5, 167.3, 161.3, 153.8, 106.1, 64.8; IR (neat) cmÀ 1 3139 (w), 3111
(w), 1737 (s), 1637 (s), 1530 (m).
°
[6] R. Meyer, J. Köhler, A. Homburg, Explosives, 6th ed.; Wiley-VCH: Weinheim,
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Acknowledgements
The authors thank the U.S. Army for financial support in carrying
out this work.
Conflict of Interest
The authors declare no conflict of interest.
Keywords: Cycloaddition Reactions
Explosives · Heterocycles · Nitric Esters
· Energetic Materials ·
Manuscript received: April 16, 2021
Revised manuscript received: May 18, 2021
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