Abrir Nitrification Progress of Nitrogen-Rich Heterocycl

molecules
Review
Nitrification Progress of Nitrogen-Rich Heterocyclic Energetic
Compounds: A Review
Yiming Luo 1,2,† , Wanwan Zheng 3,† , Xuanjun Wang 1, * and Fei Shen 1,2
1 High-Tech Institute of Xi’an, Xi’an 710025, China; iamrlym@126.com (Y.L.); shenf02@163.com (F.S.)
2 Xi’an Modern Chemistry Research Institute, Xi’an 710065, China
3 School of Chemical Engineering, Northwest University, Xi’an 710069, China; zhengwan2020@163.com
* Correspondence: wangxj503@sina.com
† These authors contributed equally to this work.
Abstract: As a momentous energetic group, a nitro group widely exists in high-energy-density

materials (HEDMs), such as trinitrotoluene (TNT), 1,3,5-triamino-2,4,6-trinitrobenzene (TATB), cyclo-
1,3,5-trimethylene-2,4,6-trinitramine (RDX), etc. The nitro group has a significant effect on improving
the oxygen balance and detonation performances of energetic materials (EMs). Moreover, the nitro
group is a strong electron-withdrawing group, and it can increase the acidity of the acidic hydrogen-
containing nitrogen-rich energetic compounds to facilitate the construction of energetic ionic salts.
Thus, it is possible to design nitro-nitrogen-rich energetic compounds with adjustable properties.
In this paper, the nitration methods of azoles, including imidazole, pyrazole, triazole, tetrazole,
and oxadiazole, as well as azines, including pyrazine, pyridazine, triazine, and tetrazine, have
been concluded. Furthermore, the prospect of the future development of nitrogen-rich heterocyclic
energetic compounds has been stated, so as to provide references for researchers who are engaged in
the synthesis of EMs.
!"#!$%&'(! Keywords: nitro group; nitration; nitrogen rich heterocycle; energetic materials
!"#$%&'
Citation: Luo, Y.; Zheng, W.; Wang,
X.; Shen, F. Nitrification Progress of
Nitrogen-Rich Heterocyclic Energetic 1. Introduction
Compounds: A Review. Molecules
Nitrogen-rich compounds have attracted widespread attention in energetic materials
2022, 27, 1465. https://doi.org/
(EMs) because of their advantages of outstanding density, excellent positive enthalpy of
10.3390/molecules27051465
formation, remarkable detonation performance, and high thermal stability [1–3]. They can
Academic Editor: Fawaz Aldabbagh be used in explosives, propellants, gas generators, and smokeless pyrotechnic fuels [4,5]. In
Received: 16 January 2022
order to meet the increasing performance requirements, new nitrogen-rich EMs are being
Accepted: 18 February 2022
developed with upgradable density, better detonation performance, lower impact and
Published: 22 February 2022
friction sensitivity, and higher thermal stability.
One of the most popular strategies for the design of promising new EMs is the incorpora-
Publisher’s Note: MDPI stays neutral
tion of both fuel and oxidizer moieties into one molecule. [6,7] The nitro group is a pivotal
with regard to jurisdictional claims in
explosive group, which exists in trinitrotoluene (TNT), 1,3,5-triamino-2,4,6-trinitrobenzene
published maps and institutional affil-
(TATB), cyclo-1,3,5-trimethylene-2,4,6-trinitramine (RDX), cyclo-1,3,5-7-tetramethylene-2,4,6,8-
iations.
tetranitr-amine (HMX), and hexanitrohexaazaisowurtzitane (CL-20), etc. Nitro groups in the
molecular structure can heighten the oxygen balance, increase the density, and significantly
enhance the detonation performance of EMs [8,9]. Moreover, the nitro group is a strong
Copyright: © 2022 by the authors.
electron-withdrawing group, and it can increase the acidity of hydrogen-containing nitrogen-
Licensee MDPI, Basel, Switzerland. rich energetic compounds and is conducive to the construction of energetic ionic salts [10].
This article is an open access article Therefore, this paper reviews the nitrification methods for nitrogen-rich heterocyclic energetic
distributed under the terms and compounds so as to give some suggestions for this special reaction.
conditions of the Creative Commons The main skeletons of nitrogen-rich heterocyclic energetic compounds are azole rings
Attribution (CC BY) license (https:// (imidazole, pyrazole, triazole, tetrazole, oxadiazole) and azine rings (pyrazine, pyridazine,
creativecommons.org/licenses/by/ triazine, tetrazine) [11,12]. Different nitration systems can be used to nitrate specific
4.0/). compounds on the basis of the structural characteristics of compounds [13]. According
Molecules 2022, 27, 1465. https://doi.org/10.3390/molecules27051465 https://www.mdpi.com/journal/molecules

Molecules 2022, 27, x FOR PEER REVIEW 2 of 20
Molecules 2022, 27, 1465 2 of 20

pyridazine, triazine, tetrazine) [11,12]. Different nitration systems can be used to nitrate
pyridazine, triazine, on
specific compounds tetrazine) [11,12].
the basis of theDifferent
structuralnitration systemsofcan
characteristics be used to
compounds nitrate
[13]. Ac‐
specific
cording compounds on the
to the diversity basis
of the of the structural
nitration positions on characteristics of compounds
these frameworks, [13].
this paper Ac‐
classi‐
to the diversity
cording of the of
to the diversity nitration positions
the nitration on these frameworks, thisthis
paper classifies
classi‐ the
fies the nitration of H on heterocyclic C,positions on these
the nitration frameworks,
of ‐NH paper
2 on heterocyclic C, the ni‐
nitration
fies the of H
nitrationon heterocyclic
of H on C, the
heterocyclic nitration
C, the of -NH
nitration of
2 on
‐NHheterocyclic C, the
2 on heterocyclic
tration of H on heterocyclic N, and the nitration of ‐NH2 on heterocyclic N. nitration
C, the ni‐ of H
on heterocyclic
tration N, and the N,
of H on heterocyclic nitration
and theof -NH2 on
nitration of heterocyclic N.
‐NH2 on heterocyclic N.
2. Nitrification of Azoles Nitrogen‐Rich Heterocyclic Energetic Compounds
2. Nitrification
2. Nitrificationof ofAzoles
AzolesNitrogen‐Rich
Nitrogen-Rich Heterocyclic
Heterocyclic Energetic
Energetic Compounds
Compounds
2.1. Imidazoles
2.1. Imidazoles
2.1. Imidazoles
2.1.1. Nitrification
2.1.1. Nitrificationof ofofHHon Imidazole Ring C
2.1.1. Nitrification H ononImidazole
Imidazole Ring
Ring C C
4,4′,5,5′‐tetranitro‐2,2′‐benzimidazole (TNBI) is an important precursor for the syn‐
4,40 ,5,50 -tetranitro-2,20 -benzimidazole (TNBI) is is
anan important precursor for the synthe-
thesis4,4′,5,5′‐tetranitro‐2,2′‐benzimidazole
of EMs. It has been synthesized by two (TNBI)
nitrificationimportant
systems.precursor for the syn‐
sis of EMs.
thesis of EMs. It has been
It has beensynthesized
synthesizedby
bytwo
two nitrification systems.
nitrification systems.
(1) NaNO3/H
(1) NaNO 3 /H 2 SO
2SO 4 system
4 system
(1) NaNO3/H2SO4 system
Klapötke et
Klapötke et al.
al. [14]
[14] synthesized
synthesized 2,2 0 -biimidazole (BI)
2,2′‐biimidazole (BI) from
from glyoxal
glyoxal and
and sodium
sodium bisulfite
bi‐
Klapötke
sulfite by et al. [14]
cyclization, synthesized
suspended NaNO2,2′‐biimidazole
and urea in (BI) from glyoxal
concentrated H SOand sodiumatbi‐0
(96–98%)
by cyclization, suspended NaNO3 and urea in concentrated H2 SO4 (96–98%) at 0 C, and
3 2 4
sulfite
°C, andby cyclization,
added suspended
BI inbatches.
small NaNO
batches. and urea inwas
The 3suspension concentrated
stirred H SOat4 (96–98%)
1 2h at 0
added BI in small The suspension was stirred for 1for
h at ambient
ambient tem‐
temperature,
°C, and added BI in small batches. The suspension was stirred for 1 h at ambient tem‐
perature,
and and then
then heated to heated
85–90 to for 16 °C
C 85–90 for 16 h. Thereafter,
h. Thereafter, the suspension
the suspension was poured wasonto
poured
crushed
perature,
onto and ice,
crushed thenfiltered,
heatedand
to 85–90
washed°C with
for 16iceh.water
Thereafter,
to theTNBIꞏ2H
obtain suspensionO, was
with poured
a yield
ice, filtered, and washed with ice water to obtain TNBI·2H2 O, with a yield of 2 51%. The
onto crushed
of 51%. The ice, filtered,
synthesis and
route washedinwith ice water to obtain TNBIꞏ2H2O, with a yield
synthesis route is shown inisScheme
shown 1. Scheme 1.
of 51%. The synthesis route is shown in Scheme 1.
Scheme 1. Synthesis
Scheme 1. 4,40 ,5,50 -tetranitro-2,20 -biimidazole
Synthesisofof4,4′,5,5′‐tetranitro‐2,2′‐biimidazole [14].[14].
Scheme 1. Synthesis of 4,4′,5,5′‐tetranitro‐2,2′‐biimidazole [14].
(2) 80%HNO
(2) 80% HNO 3 /H
3/H 2 SO
2SO 4 system
4 system∙
(2) 80% HNO3/H2SO4 system∙
Li
Lietetal.
al.[15]
[15]synthesized
synthesizedBIBIusing using ammonium
ammonium acetate
acetate 3COONH4) and glyoxal as
(CH(CH
3 COONH4 ) and glyoxal as
raw Li
raw
et al. [15]
materials.
materials.
synthesized
Then,
Then, BIBIwas
was
BI using
added
added totoammonium
95–98%
95–98%
acetate (CH
concentrated
concentrated H2SO3COONH4) and glyoxal as
H 4 at 20–25 °C. After that,
SO
raw materials. Then,ofBI80%wasHNO
added to 95–98% concentrated H2SO42 at 20–25 4 at 20–25 C. After that,
°C. After that,
the mixed
the mixed solution
solution of 80% HNO 3 and 95–98% H2SO4 was added dropwise as the mixture
and 95–98% H SO was added dropwise as the mixture
the 3 2 4
wasmixed
was heated
heated
solution
to
to45
45 °C.of
C.
80% hours
Four
Four
HNO3later,
hours
and 95–98%
thethe
later,
H2SOsolution
reaction
reaction
4 was added dropwise as the mixture
solutionwaswas
poured ontoonto
poured crushed ice,
crushed
was heated
filtered, to 45 with
washed °C. Four
coldhours
water,later, the reaction
and dried solution
to obtain TNBI.was The poured
synthesis onto crushed
route is shownice, ice,
filtered, washed
filtered, washed withcold cold water,and anddried
driedtotoobtain
obtainTNBI.
TNBI. The synthesis route is shown in
in Scheme 2. Thewith yield waswater,
51.7%. Compared with the The
traditional synthesis
operation route is shown
process [14],
Scheme
in Scheme 2. 2.
TheTheyield
yield was
was51.7%.
51.7%. Compared
Compared with
with the
the traditional
traditional operationprocess
operation process[14],
[14], this
this strategy saves the reaction time and lowers the reaction temperature via a gentle and
strategy
this saves
strategy the the
saves reaction time
reaction andand
time lowers
lowersthethe
reaction
reaction temperature
temperature via a agentle
via gentle and
and stable
stable reaction process, thus, the danger of the reaction is reduced.
reaction
stable process,
reaction thus, thus,
process, the danger of the
the danger of reaction is reduced.
the reaction is reduced.
Scheme 2. Synthesis of 4,4′,5,5′‐tetranitro‐2,2′‐biimidazole [15].

Scheme 2.2.Synthesis
Scheme 4,40 ,5,50 -tetranitro-2,20 -biimidazole
Synthesisofof4,4′,5,5′‐tetranitro‐2,2′‐biimidazole [15].[15].
2.1.2. Nitration of ‐NH2 on Imidazole Ring C/N
2.1.2. Nitration
2.1.2. Nitrationofof‐NH-NH 2 on
2 on Imidazole
Imidazole Ring
Ring C/N C/N
The H atom of NH2 can be nitrified to obtain different nitration products using the
The HHatom
atomofofNH NH 2 can bebe nitrified
to to obtain different nitration products
usingusing
the the
HNOThe 3/H2SO4 system.
2 can nitrified obtain different nitration products
HNOThomas
HNO /H
33/H 2 SO
2SO system.
4 system.
4
et al. [16] added 2‐aminobenzimidazole (1) to the solution of 100% HNO3
Thomasetetal.
Thomas
and concentrated al. [16]added
H[16] added2‐aminobenzimidazole
2-aminobenzimidazole (1)the
(1) to to the solution
solution of 100%
of 100%
2SO4 (96–98%) while stirring at 0 °C. After stirring for 48 h at 25 °C,
HNOHNO 3 3
and
and concentrated
concentrated
the mixture was poured H H2SOSO (96–98%)
(96–98%)
2 onto
4 4 while
while stirring
stirring at 0 at 0
°C. C.
AfterAfter stirring
stirring
crushed ice, then filtered and washed with 20% HNO for for
48 h 48
at h3 and
25 at
°C,25 C,
the mixture
the mixture was waspoured
pouredonto ontocrushed
crushedice,
ice,then
thenfiltered
filteredandand washed
washed with
with 20%20%
HNOHNO 3 and a
3 and
small amount of water. The light yellow solid, 2-nitroammonium-5,6-dinitrobenz imidazole

(2), was obtained with a yield of 41%. The synthesis route is shown in Scheme 3.
Molecules 2022, 27, 1465 3 of 20

a small amount of water. The light yellow solid, 2 nitroammonium 5,6 dinitrobenz im
aidazole
small amount
(2), wasofobtained
water. The light
with yellow
a yield of solid, 2 nitroammonium
41%. The 5,6isdinitrobenz
synthesis route im
shown in Scheme 3.
idazole (2), was obtained with a yield of 41%. The synthesis route is shown in Scheme 3.
Scheme
Scheme Synthesis
3.Synthesis
Scheme3.3. Synthesis 2ofnitrimino
of of 22-nitrimino-5,6-dinitrobenzimidazole
nitrimino
5,6 5,6 dinitrobenzimidazole
dinitrobenzimidazole [16].
[16]. [16].
Another
Anotherexample
Another example
example is nitration
is is nitration
nitration of ofof -NH
NH NH on imidazole
on
2 on22imidazoleimidazole
ring N. ring
ringYinN.N. Yin
etYin et al.
et
al. [17] al. [17] synthe
[17]
synthe synthesized
4,4 0 ,5,54,4
0 ,5,5 tetranitro 01H,1 H 0(2,2 0 -diamine
sized
sized 4,4-tetranitro-1H,1
,5,5 tetranitro 1H,1 H-(2,2
H (2,2 -benzimidazole)-1,1
benzimidazole)
benzimidazole) 1,1
1,1 diamine (4) (4)
diamine from
(4)
from from glyoxal
glyoxal and and
glyoxal ammo-
and
nium
ammonium
ammonium acetate by using
acetate
acetate byby usingcondensation,
using condensation,
condensation, nitration,
nitration,
nitration, and
and N N-amination
and N amination
amination reactions.
reactions. ComCompound
reactions. Com 4
was
pound
pound then
44wasslowly
was then
then added
slowly
slowly toadded
theto
added HNO
the 3 /H
HNO
to the HNO SO2SO
23/H solution
43/H 4 2solution atat 10
SO4 solution 10at°CCandand
10 °C stirred
stirred forfor
and stirred 90 90formin.
90 The
min.
min. The
solution Thewassolution
solution was
subsequently
was subsequently
poured
subsequently poured
onto
poured ontoonto
crushedcrushedice,
crushedice,
stirredstirred
ice,for for
about
stirred about 10–15
10–15
for about min, filtered,
10–15
min, filtered, and washed
washedwith ice cooled water, ethanol, and ether to obtain
and0 -dinitroamino-4,4
to obtain0 ,5,50 -
and
min,washedfiltered, with and ice-cooled water,
with ethanol,
ice cooled andwater,
ether toethanol,
obtain N,N ether
N,N’
N,N’dinitroamino
dinitroamino4,44,4 ,5,5,5,5
tetranitro bisimidazole (5). The synthesis route is shown in
tetranitro-bisimidazole (5).tetranitro
The synthesis route is(5).
bisimidazole shown
Scheme 4. In order to prevent the N N bond from being broken, the nitration reaction
The in Schemeroute
synthesis 4. In isorder
shown to prevent
in
Scheme
the N-N 4. In order
bond from to prevent
being the Nthe
broken, N nitration
bond from being broken,
reaction should the
be nitration reaction
performed in a mixed
should be performed in a mixed acid at a temperature of 15 to 10 °C because the
should
acid at abetemperature
performed in of a 15mixed
to acid
10 Catbecause
a temperature
the of 15 group
N-amino to 10 is°Chighly because the
reactive. It
N amino group is highly reactive. It has been found that the nitrification ability of
N amino
has been group
found is highly
that the reactive.
nitrification It has been
ability of HNO found /H that
SO the
is nitrification
stronger than ability
that of of
HNO
HNO 3/H2SO 4 is stronger than that of HNO 3, so HNO 3/H2SO3 4 with
2 an
4 appropriate ratio is 3,
HNO
so HNO 3/H2SO4 is stronger than that of HNO3, so HNO3/H2SO4 with an appropriate ratio is
always 3 /H2 SO
selected with an NH
for4 nitrating appropriate
2 to NHNO ratio
2. Theisreaction
always condition
selected for nitrating
is mostly mildNH and2 to NHNO2 .
always
The
the selected
reaction
operation for nitrating
iscondition
simple. NH2 mild
is mostly to NHNOand the2. The reaction condition is mostly mild and
operation is simple.
the operation is simple.
Scheme Synthesis
Scheme 4.4.Synthesis of N,N
of N,N’ 0 -dinitramino-4,4
dinitramino 0 ,5,50 -tetranitro-bisimidazole
4,4 ,5,5 tetranitro bisimidazole [17]. [17].
2.1.3.
2.1.3.
Scheme Nitrification
Nitrification ofN,N’
of of
4. Synthesis H H Imidazole
on on Imidazole Ring
Ring4,4
dinitramino N N
,5,5 tetranitro bisimidazole [17].
(1) HNO /Ac O system
3 2
(1)
2.1.3.HNO 3/Ac2O system
Nitrification of H on Imidazole Ring N
Chandetet
Chand al.al.
[18][18] synthesized
synthesized compound
compound using benzimidazole
7 using7benzimidazole as a raw material
as a raw material
through
through
(1) HNO iodination,
iodination,
3/Ac2O system nitration,
nitration, substitution,
substitution, andand
ringring formation
formation reactions
reactions (Scheme
(Scheme 5). 5). Then,
100% HNO
Then, 100% HNO
3 was added
3 was addeddropwise
dropwisetotoacetic
acetic anhydride
anhydride (Ac (Ac
2O)O)
2 at at
Chand et al. [18] synthesized compound 7 using benzimidazole as a raw material
5 °C,5andC, and
the rethe resulting
sulting mixture
mixture was stirred for 0.5 h. Compound 77 was then added to the reaction solu solution in
through was stirred
iodination, for 0.5
nitration, h. substitution,
Compound andwas then
ring added
formation to the reaction
reactions (Scheme 5).
tion in portions and stirred for 2 h. Afterwards, the reaction mixture was poured onto
portions
Then, 100%andHNO stirred foradded
3 was 2 h. Afterwards,
dropwise tothe reaction
acetic mixture
anhydride (Acwas
2O) atpoured
5 °C, onto
and crushed
the re ice.
crushed ice. Compound 8 was obtained by filtration with a yield of 67%. Compared with
Compound
sulting mixture8 waswas obtained
stirred by
for filtration
0.5 h. with
Compound a yield
7 was of 67%.
then Compared
added
the nitrifying agent HNO3/H2SO4, the nitrifying ability of HNO3/Ac2O mixed solution is to the with
reactionthe nitrifying
solu
agent
tion inHNO
weaker, but Ac 3 /H
portions 2O can
SOeffectively
2and , the nitrifying
4stirred for ability
2 h. Afterwards,
decrease of HNO
the oxidizingthe /Ac2 of
O HNO
3reaction
property mixed
mixture solution
3 andwas is weaker,
poured
avoid the onto but
Ac O
crushed
2 can
formation effectively
ice. Compound
of by decrease
products of8 compound the oxidizing
was obtained 8. by filtration with a yield3 of 67%. Compared with of
property of HNO and avoid the formation
by-products
the nitrifyingofagentcompound
HNO3/H 8.2SO4, the nitrifying ability of HNO3/Ac2O mixed solution is
weaker, but Ac2O can effectively decrease the oxidizing property of HNO3 and avoid the
formation of by products of compound 8.
Scheme 5. Synthesis
Scheme 5. of 7-nitro-7H-imidazo[4
Synthesis of 0 ,5,5,6]benzo[1–4]bis([1,2,5]oxadiazole)-3,4-dioxide
7 nitro 7H imidazo[4 ,5,5,6]benzo[1–4]bis([1,2,5]oxadiazole) 3,4 dioxide [18].
[18].
2.2. Nitrification of Pyrazoles

2.2.1. Nitrification of H on Pyrazole Ring C
(1) Bismuth nitrate/montmorillonite

P. Ravi et al. [19] added 1 methylpyrazole 2 oxide and montmorillonite (K 10) to a
Scheme 5. Synthesis of 7‐nitro‐7H‐imidazo[4′,5,5,6]benzo[1–4]bis([1,2,5]oxadiazole)‐3,4‐dioxide
[18].
2.2. Nitrification
Scheme of Pyrazoles
5. Synthesis of 7‐nitro‐7H‐imidazo[4′,5,5,6]benzo[1–4]bis([1,2,5]oxadiazole)‐3,4‐dioxide
[18]. Nitrification of H on Pyrazole Ring C
2.2.1.
Molecules 2022, 27, 1465 2.2. Nitrification

(1) of Pyrazoles
Bismuth nitrate/montmorillonite 4 of 20
2.2.1.P.Nitrification
Ravi et al. [19] of Hadded
on Pyrazole Ring C
1‐methylpyrazole‐2‐oxide and montmorillonite (K‐10) to a
suspension of bismuth nitrate (Bi(NO3)3) in tetrahydrofuran (THF) and stirred for 2.5 h.
2.2.
(1) Nitrification
The Bismuthwas
solvent of Pyrazoles
nitrate/montmorillonite
then evaporated under reduced pressure using a vacuum pump for 5
2.2.1. Nitrification of H on Pyrazole Ring C
min. P.The Ravimixture was added
et al. [19] repeatedly washed with dichloromethane
1‐methylpyrazole‐2‐oxide (CH2Cl2) and
and montmorillonite concen‐
(K‐10) to a
(1)
tratedBismuth
to give nitrate/montmorillonite
suspension ofthe crude nitrate
bismuth K‐10. The (Bi(NO pure3)product was isolated by
3) in tetrahydrofuran column
(THF) and chromatography
stirred for 2.5 h.
withP.solvent
The aRavi
yield et was
al. 98%.
of [19] added
then The 1-methylpyrazole-2-oxide
synthesis
evaporated route is
under shownand
reduced in montmorillonite
Scheme
pressure 6. The
using (K-10) to pump
ranking
a vacuum aof nitration
for 5
suspension
capacities of
of bismuth
some nitrate
nitrates (Bi(NO
is as 3 ) 3
follows:) in tetrahydrofuran
Bi(NO )
min. The mixture was repeatedly washed with dichloromethane (CH2Cl2) and concen‐
3 3＞AgNO (THF) 3
and
＞KNO stirred
3
for
＞NaNO 2.5 h.
3 ＞NH 4NO3
The solvent was then evaporated under reduced pressure using a vacuum pump for 5 min.
＞Pb(NO
trated to give3)2＞Ba(NO
the crude3)2. K‐10.
In theThe pure product
reaction, Bi(NO3)was isolated
3, which by column chromatography
is impregnated on K‐10, has a
The mixture was repeatedly washed with dichloromethane (CH2 Cl2 ) and concentrated to
with
give a
fast the yield
nitration of
crude K-10. 98%.
rateThe The
andpure
highsynthesis
yieldwas
product androute is
is easy
isolated shown
by to in Scheme
separate
column 6. The
from the product
chromatography ranking by
with a yield offiltration.
nitration
capacities
The
of 98%. The of
methyl some in
group
synthesis nitrates
the is
route is as follows:
pyrazole
shown inringScheme Bi(NO
contributes 3＞AgNO
6. The3)ranking
to the of 3＞KNO
nitration
nitration 3＞NaNO
process,
capacities and3＞NH
of 4NO3
the nitra‐
some
＞Pb(NOnitrates
tion rate will isincrease
as follows:
3)2＞Ba(NO . Bi(NO
In the3 )number
3)2with 3 > AgNO
reaction, of
3 > KNO
Bi(NO
methyl 3)
3 3>
, NaNO
which
groups. 3 >
is NH NO
impregnated
4 3 > Pb(NOon )
3 2K‐10, has a
>fast
Ba(NO )
3 2
nitration. In the reaction, Bi(NO
rate and high yield ) , which is impregnated on K-10, has a
3 3 and is easy to separate from the product by filtration. fast nitration
rate and high yield and is easy to separate from the product by filtration. The methyl group
The methyl group in the pyrazole ring contributes to the nitration process, and the nitra‐
in the pyrazole ring contributes to the nitration process, and the nitration rate will increase
tion rate will increase with the number of methyl groups.
with the number of methyl groups.
Scheme 6. Synthesis of 1‐methyl‐5‐nitropyrazole‐ 2‐oxide (K‐10) [19].
(2) HNO3/H2SO4 system

Scheme
Scheme 6.6.Synthesis
The Synthesis
HNO of 21-methyl-5-nitropyrazole-
3/H of 4 system usually 2-oxide
SO1‐methyl‐5‐nitropyrazole‐ (K-10)
has a2‐oxide
strong[19].
(K‐10) [19].
nitration effect. Fischer et al. [20]
synthesized 4‐chloropyrazole
(2) HNO3 /H2 SO4 system (9) using pyrazole as a raw material via chlorination reac‐
(2) HNO 3 /H 2 SO 4 system
tion. Compound 9 was then dissolved in the concentrated H2SO4, and 100% HNO3 was
The HNO3 /H2 SO4 system usually has a strong nitration effect. Fischer et al. [20]
slowlyThe added
HNObelow 3/H2SO40 °C. Then,
4 system the mixture
usually was heated
has a strong to 100
nitration °C and
effect. stirred
Fischer for [20]
et al. 5h
synthesized 4-chloropyrazole (9) using pyrazole as a raw material via chlorination reaction.
synthesized
under reflux.
Compound 4‐chloropyrazole
9 was After cooling to
then dissolved in(9)
theusing
room pyrazole
temperature,
concentrated as 4athe
H2 SO raw
, and material
final
100% HNO3via
solutionwaschlorination
was poured reac‐
slowly onto
tion.
added
crushedCompound
below
ice40 water 9 and
wasthe
C. Then, then dissolved
mixture
extracted was in the
withheated concentrated
to 100
acetoacetic Cacid. The H
and stirred 2SO
for , and
54h
organic under 100%
layers reflux.
wereHNO 3 was
washed
After
with cooling
slowly added
water, to room
below
dried temperature,
40
over the final
°C. magnesium
Then, solution
the mixture was
was
sulfate, poured
andheated onto
dried crushed
to 100
under ice
°C and water
stirredtoforgive
nitrogen 5h
and extracted with acetoacetic
4‐chloro‐3,5‐dinitro‐1H‐pyrazole
under reflux. After cooling to room acid. The organic layers
(10) intemperature,were washed
a yield of 86.7%. with water,
The synthesis
the final dried
solution was over
routepoured
is shown in
onto
magnesium
Scheme
crushed 7. icesulfate,
The
water and dried
reaction isunder
and extracted nitrogen
simple, to give 4-chloro-3,5-dinitro-1H-pyrazole
no acetoacetic
with further purification
acid. Theisorganic
required, and(10)
layers the reaction
were washed
in a yield of 86.7%. The synthesis route is shown in Scheme 7. The reaction is simple, no
yield
with iswater,
high. dried over magnesium sulfate, and dried under nitrogen to give
further purification is required, and the reaction yield is high.
4‐chloro‐3,5‐dinitro‐1H‐pyrazole (10) in a yield of 86.7%. The synthesis route is shown in
Scheme 7. The reaction is simple, no further purification is required, and the reaction
yield is high.
Scheme 7. Synthesis of 4-chloro-3,5-dinitropyrazole [20].

Scheme 7. Synthesis of 4‐chloro‐3,5‐dinitropyrazole [20].
(3) HNO3 /P2 O5 system
Wang et al. [21] dissolved P2 O5 in fuming HNO3 and then added (6-(3,5-dimethyl-1H-
Scheme 7. Synthesis of 4‐chloro‐3,5‐dinitropyrazole [20]. (11) at 0 C. The reaction mix-
pyrazole-1-yl)-1,2,4-triazole[4,3-b]-1,2,4,5-tetrazine-3-amino
ture was stirred for 10 h at room temperature. Then, the mixture was subsequently poured
onto crushed ice, extracted with ethyl acetate, and purified by column chromatography to
obtain N-(6-(3,5-dimethyl- 4-nitro-1H-pyrazole-1-yl)-1,2,4-triazolo[4,3-b]-1,2,4,5-tetrazin-3-
yl)nitramide (12) with a yield of 58%. In this reaction, the NH2 in 1,2,4-triazol ring is also
nitrated to NHNO2 . The synthesis route is shown in Scheme 8. The nitrification system
used in this reaction is HNO3 /P2 O5 . P2 O5 is not only a dehydrating agent, but also a
nitrification promoter. This nitration system is not only suitable for aromatics but also for
amines. Even amines that are difficult to nitrate can get satisfactory results sometimes.
0 °C.Wang et al.mixture
The reaction [21] was
dissolved P2O10
stirred for 5
hinat room
fuming HNO3 and
temperature. Then,then added
the mixture
(6‐(3,5‐dimethyl‐1H‐ pyrazole‐1‐yl)‐1,2,4‐triazole[4,3‐b]‐1,2,4,5‐tetrazine‐3‐amino
was subsequently poured onto crushed ice, extracted with ethyl acetate, and purified by (11) at
0 °C.
column The reaction mixture was
chromatography stirred for 10
to h at room temperature.
obtain Then, the mixture
N‐(6‐(3,5‐dimethyl‐
was subsequently poured onto crushed ice, extracted with ethyl acetate, and(12)
4‐nitro‐1H‐pyrazole‐1‐yl)‐1,2,4‐triazolo[4,3‐b]‐1,2,4,5‐tetrazin‐3‐yl)nitramide purified
withby a
column
yield chromatography
of 58%. In this to
reaction, the NH2 in 1,2,4‐triazol obtain
ring N‐(6‐(3,5‐dimethyl‐
is also nitrated to NHNO2. The
4‐nitro‐1H‐pyrazole‐1‐yl)‐1,2,4‐triazolo[4,3‐b]‐1,2,4,5‐tetrazin‐3‐yl)nitramide
synthesis route is shown in Scheme 8. The nitrification system used in this(12) with isa
reaction
yield of 58%. In this reaction, the NH 2 in 1,2,4‐triazol ring is also nitrated to NHNO2. The
HNO3/P2O5. P2O5 is not only a dehydrating agent, but also a nitrification promoter. This
synthesissystem
nitration route isis shown
not onlyinsuitable
Schemefor 8. The nitrification
aromatics but alsosystem used in
for amines. thisamines
Even reaction is
that
HNO 3/P2O5. P2O5 is not only a dehydrating agent, but also a nitrification promoter. This
are difficult to nitrate can get satisfactory results sometimes.
Molecules 2022, 27, 1465 5 of 20
nitration system is not only suitable for aromatics but also for amines. Even amines that
are difficult to nitrate can get satisfactory results sometimes.
Scheme 8. Synthesis of N‐(6‐(3,5‐dimethyl‐4‐nitro‐1H‐pyrazol‐1‐yl)

‐1,2,4‐triazolo[4,3‐b]‐1,2,4,5‐tetrazine‐3‐yl)nitramide [21].
Scheme 8. Synthesis
Scheme 8. of Synthesis
N-(6-(3,5-dimethyl-4-nitro-1H-pyrazol-1-yl)
of -1,2,4-triazolo[4,3-b]-1,2,4,5-
N‐(6‐(3,5‐dimethyl‐4‐nitro‐1H‐pyrazol‐1‐yl)
tetrazine-3-yl)nitramide
2.2.2. Nitrification of ‐NH [21].
‐1,2,4‐triazolo[4,3‐b]‐1,2,4,5‐tetrazine‐3‐yl)nitramide
on Pyrazole Ring C [21].
2.2.2. Nitrificationofof‐NH
2.2.2. Nitrification -NHononPyrazole
Pyrazole Ring
Ring CC
(1) 100% HNO3 system
(1) HNO100%3 HNO 3 system
is a strong nitration agent, it can be used to nitrate NH2 to NHNO2. Yin et al.
[22] HNO is
synthesized
3 a strong nitration agent, it can be used to nitrate NH2 to(14)
1,1′‐(ethane‐1,2‐diyl)bis(3,5‐dinitro‐)1H‐pyrazole‐4‐amine) NHNOusing 2 . Yin
et al. HNO 3 is a strong nitration
[22] as
pyrazole synthesized
raw material 1,1through agent, it can be used
halogenation, to nitrate
nitration, NH2 to NHNO
0 -(ethane-1,2-diyl)bis(3,5-dinitro-)1H-pyrazole-4-amine)
neutralization, . Yin (14)
et al.using
and 2alkylation
[22] synthesized
pyrazole
reaction. Afterwards, 1,1′‐(ethane‐1,2‐diyl)bis(3,5‐dinitro‐)1H‐pyrazole‐4‐amine)
as raw material compound through14 halogenation,
was added to 100%nitration,
HNOneutralization, (14)
and10
3 in portions below
using
alkylation
°C.
pyrazole as raw material through halogenation, nitration, neutralization, and in
alkylation
reaction. Afterwards, compound 14 was added to 100% HNO3 in portions below
The reaction was held for 10 min at 5 °C, and HNO 3 was removed by blowing air. The10 C.
reaction. Afterwards, compound 14 was added to 100% vacuumHNO3 in portions below 10give °C.
The reaction was
residue was held for 10 min at 5 C,under
dried and HNO3 was removed by to blowing in air. The
The reaction was held for 10 min at 5 °C, and HNO 3 was removed by blowing in air. The
residue was dried under vacuum to give N,N 0 -[1,10 -(ethane-1,2-diyl)bis(3,5-dinitro-1H-
N,N’‐[1,1′‐(ethane‐1,2‐diyl)bis(3,5‐dinitro‐1H‐‐pyrazole‐4,1‐diyl)]dinitramide (15). The
residue route was
synthesis is shown in dried
Scheme 9. under
This process vacuum
uses 100% HNO to give
3 as the nitration
pyrazole-4,1-diyl)]dinitramide (15). The synthesis route is shown in Scheme 9. This process
N,N’‐[1,1′‐(ethane‐1,2‐diyl)bis(3,5‐dinitro‐1H‐‐pyrazole‐4,1‐diyl)]dinitramide
system. ForHNOthe nitration of different azoleFor
rings, (15). The
uses 100% 3 as the nitration system. the different
nitration concentrations
of different azoleof HNO are
rings,3 different
synthesis route is
required. shown in Scheme 9. This process uses 100% HNO3 as the nitration
concentrations of HNO are required.
system. For the nitration3 of different azole rings, different concentrations of HNO3 are
required.
Scheme 9. Synthesis
Scheme 9. of N,N0 -[1,10 -(ethane-1,2-diyl)bis(3,5-dinitro-1H-pyrazole-4,1-diyl)]dinitramide [22].
Synthesisof
N,N’‐[1,1′‐(ethane‐1,2‐diyl)bis(3,5‐dinitro‐1H‐pyrazole‐4,1‐diyl)]dinitramide [22].
(2) 70%
Scheme HNO3 /H
9. Synthesis of2 SO4 system
N,N’‐[1,1′‐(ethane‐1,2‐diyl)bis(3,5‐dinitro‐1H‐pyrazole‐4,1‐diyl)]dinitramide
(2) 70% HNO3/H2SO4 system [22].
Molecules 2022, 27, x FOR PEER REVIEW Zhang et al. [23] added 4-amino-3,5-dinitropyrazole (16) to a mixture of HNO 6 of 320(70%)
and concentrated
Zhang et al. [23]H 2
(2) 70% HNO3/H2SO4 system SO
added
4 in a volume ratio of 1:1 at
4‐amino‐3,5‐dinitropyrazole 0 C. The
(16) mixture
to was
a mixture stirred
of HNOfor 3 2h
and then slowly warmed to room temperature. After stirring for another 4 h, the reaction
(70%) and concentrated H 2SO 4 in a volume ratio of 1:1 at 0 °C. The mixture was stirred
for 2 Zhang
h and
mixture
reaction was
et al.slowly
then
poured
[23] added
wasintowarmed 4‐amino‐3,5‐dinitropyrazole
to room
ice water ice temperature.
and extracted After
with
(16) to afor
stirring
ether to
mixture
another
obtain
of HNO
h, the3
to 4stirred
4-nitroamino-3,5-
(70%) andmixture
concentrated poured
H2SO4 ininto a volume water and
ratio of 1:1extracted
at 0 °C. The with ether
mixture was obtain
dinitropyrazole (17). The synthesis
4‐nitroamino‐3,5‐dinitropyrazole (17).route is shownroute
The synthesis in Scheme
is shown10. in Scheme 10.
for 2 h and then slowly warmed to room temperature. After stirring for another 4 h, the
Scheme Synthesisofof4‐nitramino‐3,5‐dinitropyrazole
10.Synthesis
Scheme 10. 4-nitramino-3,5-dinitropyrazole[23].[23].
(3) HNO3/Ac
(3) HNO 3 /Ac O system
2O2system
He etetal. al.
He [23] synthesized 4-methylamino-3,5-dinitropyrazole
[23] synthesized 4‐methylamino‐3,5‐dinitropyrazole (18) using
(18) 4-chloro-3,5-
using
dinitro pyrazole (10)
4‐chloro‐3,5‐dinitro as a raw(10)
pyrazole material through
as a raw nucleophilic
material substitutionsubstitution
through nucleophilic reaction. Firstly,
100% HNO
reaction. 3 was
Firstly, slowly
100% HNOadded
3 was to a cooled
slowly solution
added of compound
to a cooled solution of18 in acetic acid,
compound 18 in after
which Ac2 O was added, and the mixture was stirred for 1.5 h at room temperature. 4-(N-
acetic acid, after which Ac 2O was added, and the mixture was stirred for 1.5 h at room
methylnitramino)-3,5-dinitropyrazole (19) was finally obtained
temperature. 4‐(N‐methylnitramino)‐3,5‐dinitropyrazole (19) was by removing
finally obtainedexcess
by acid
removing
under excess
vacuum acida under
with yield ofvacuum
95%. Thewith a yield route
synthesis of 95%. The synthesis
is shown route
in Scheme 11.isThis
shownreaction
in Scheme
uses HNO311. /Ac This reaction uses HNO3/Ac2O as a nitration system, which is simple to
2 O as a nitration system, which is simple to operate, has no by-products,
operate,
and has noisby‐products,
the yield as high as 95%.and the yield is as high as 95%.
Scheme 10. Synthesis of 4‐nitramino‐3,5‐dinitropyrazole [23].
(3) HNO3/Ac2O system
He et al. [23] synthesized 4‐methylamino‐3,5‐dinitropyrazole (18) using
4‐chloro‐3,5‐dinitro He et al.(10)[23]
pyrazole as asynthesized
raw material 4‐methylamino‐3,5‐dinitropyrazole
through nucleophilic substitution (18) using
4‐chloro‐3,5‐dinitro pyrazole (10) as a raw material through nucleophilic substitution
reaction. Firstly, 100% HNO3 was slowly added to a cooled solution of compound 18 in
reaction. Firstly, 100% HNO3 was slowly added to a cooled solution of compound 18 in
acetic acid, after which Ac2O was added, and the mixture was stirred for 1.5 h at room
acetic acid, after which Ac2O was added, and the mixture was stirred for 1.5 h at room
temperature. 4‐(N‐methylnitramino)‐3,5‐dinitropyrazole (19) was finally
temperature. 4‐(N‐methylnitramino)‐3,5‐dinitropyrazole obtained
(19) was by
finally obtained by
removing excess acid under vacuum with a yield of 95%. The synthesis route
removing excess acid under vacuum with a yield of 95%. The synthesis routeis shown is shown
Molecules 2022, 27, 1465 6 of 20
in Scheme 11. This reaction
in Scheme 11. uses HNO3/Ac
This reaction 2O HNO
uses as a nitration
3/Ac2O as system, which
a nitration is simple
system, which istosimple to
operate, has no operate,
by‐products, and the yield is as high as 95%.
has no by‐products, and the yield is as high as 95%.
Scheme 11. Synthesis of 4‐(N‐methylnitramino)‐3,5‐dinitropyrazole [24].

Scheme 11. Synthesis
Scheme 11. of 4‐(N‐methylnitramino)‐3,5‐dinitropyrazole
Synthesis of 4-(N-methylnitramino)-3,5-dinitropyrazole [24].
[24].
2.2.3. Nitrification of Nitrification

2.2.3. H on Pyrazole of HRing N
on Pyrazole Ring N
2.2.3. Nitrification of H on Pyrazole Ring N
(1) HNO3 /Ac2 O system
(1) Tang
HNO3et /Ac
al.2O[25]
system
synthesized
Tang et al. [25]1H,1
0 H-3,30 -bispyrazole(20) using oxalyl chloride and
synthesized 1H,1′H‐3,3′‐bispyrazole(20) using oxalyl chloride and
ethoxyethylene as rawsynthesized
materials
Tang et al.ethoxyethylene
[25] as through addition, elimination,
1H,1′H‐3,3′‐bispyrazole(20)
raw materials through and
using
addition, cyclization
oxalyl
elimination, andreactions.
chloride and
cyclization reac‐
Firstly, 100% HNO
ethoxyethylene tions. was
as 3 raw added
materials
Firstly, 100%dropwise
through
HNO 3 wasto addition,
AC2 O dropwise
added at 0elimination,
C, then
to AC compound
2O and °C, 20 was
at 0 cyclization
then slowly
reac‐ 20 was
compound
added to the mixed
tions. Firstly, slowly
100% acid.
HNOadded The
3 was reaction
to the mixed
added mixture was
acid. Theto
dropwise ACwarmed
reaction mixture
2O at to then
0 °C, room
was temperature,
warmed
compound to room and
temperature,
20 was
stirred
slowly for 6 h. to
added Thethereaction
and stirred
mixed for mixture
6 h.
acid. The was
The subsequently
reaction
reaction mixturewas
mixture poured
waswarmedinto ice
subsequently water,
to room pouredfiltered, and
into ice
temperature, water, fil‐
washed withfor
trifluoroacetic acid (TFAA) to obtain 0
1,1 -dinitro-1H, 0
1 H-3,3 0 -bispyrazole
and stirred tered, and washed
6 h. The reaction with
mixture trifluoroacetic
was subsequently acid (TFAA)
poured to
into ice water, (21),
obtain 1,1′‐dinitro‐1H,
fil‐
with
tered,a yield 1′H‐3,3′‐bispyrazole
and ofwashed
71%. Thewith
synthesis (21),
routewith
trifluoroacetic a yield
is shown of(TFAA)
acid in 71%. The12.
Scheme synthesis
to obtainroute is shown in Scheme 12.
1,1′‐dinitro‐1H,
1′H‐3,3′‐bispyrazole (21), with a yield of 71%. The synthesis route is shown in Scheme 12.
Scheme 12. Synthesis 12.0 -dinitro-1H,1H’-3,3

of 1,1
Scheme 0 -bipyrazole [25].
Synthesis of 1,1′‐dinitro‐1H,1H’‐3,3′‐bipyrazole [25].
(2) NH4 NO3 /TFAA

(2) NHsystem
4NO3/TFAA system
Scheme 12. Synthesis of 1,1′‐dinitro‐1H,1H’‐3,3′‐bipyrazole [25].
Molecules 2022, 27, x FOR PEER REVIEW Kumar et al. [26] Kumar et al.4,4
prepared 0 -dinitro-1H,1
[26] 0 H-3,30 -bipyrazole (22) by nitrating
prepared 4,4′‐dinitro‐1H,1′H‐3,3′‐bipyrazole 7(22) by nitrating bi‐
bipyra-
of 20
zole
(2) (20)
NH4with pyrazole
nitric–sulfur
NO3/TFAA (20) mixed
system with nitric–sulfur mixed
acid. Then, NH4acid.
NO3Then, NH4NOto
was added 3 was added to the suspension
the suspension of
compound of compound 5 in TFAA ((CF3CO)2O) in batches at 0–5 °C. The reaction mixture was
in al.
TFAA
Kumar5 et [26]((CF 3 CO)2 O)
prepared in batches at 0–5 C. The reaction(22)
4,4′‐dinitro‐1H,1′H‐3,3′‐bipyrazole mixture was stirred
by nitrating bi‐
for 5 h at room temperature, filtered, and washed with water to obtain 1,1 0 ,4,40 -tetranitro-
stirred for 5 h at room temperature, filtered, and washed with water
pyrazole (20) with nitric–sulfur mixed acid. Then, NH4NO3 was added to the suspension to obtain
1H,1 0 H-3,30 -dipyrazole (23). The synthesis route is shown in Scheme 13. NH NO /TFAA
1,1′,4,4′‐tetranitro‐1H,1′H‐3,3′‐dipyrazole
of compound 5 in TFAA ((CF3CO)2O) (23). The synthesis
in batches route
at 0–5 °C. is reaction
The shown inmixture
4Scheme3 was
are used
13. NH 4NOas3/TFAA
nitrationare reagents to makereagents
used as nitration reactiontoconditions mild,
make reaction and post-treatment
conditions mild, and of
waste acid is not
post‐treatment needed
of waste at the
acid end
is not of theatreaction.
needed the end of the reaction.
Scheme 13.Synthesis
Scheme 13. 4,40 ,5,50 -tetranitro-2H,20 H-3,30 -bipyrazole
Synthesisofof4,4′,5,5′‐tetranitro‐2H,2′H‐3,3′‐bipyrazole [26]. [26].
2.2.4. Nitrificationofof‐NH
2.2.4. Nitrification -NH 2 Connected
2 Connected
with
with thethe Pyrazole
Pyrazole RingRing
N N
A fuming
A fumingHNO HNO 3 /con.
3/con. H2SOH24SO 4 system
system canused
can be be used to nitrate
to nitrate –NH2 -NH 2 to NHNO
to NHNO 2 , is
2, which
which
is connected
connected with
with Nainpyrazole
N in a pyrazole
ring.ring.
Yin et
Yin et al.
al. [27]
[27] cooled
cooledaaconcentrated
concentratedHH 2 SO
2SO 4 suspension
4 suspension
of 3,6-dinitropyrazole[4,3-c]
of 3,6‐dinitropyrazole[4,3‐c]
pyrazole-1,4-diamine (24) to 15 C in an ice-salt bath,
pyrazole‐1,4‐diamine (24) to −15°C in an ice‐salt bath, then fuming then fumingHNO HNO
3 was 3 was
added added
dropwise 0
dropwise to the mixture. After the mixture was stirred for 2 h at −15 °C, -(3,6-
to the mixture. After the mixture was stirred for 2 h at 15 C, N,N
dinitropyrazole[4,3-c] pyrazole-1,4-diyl)dinitramine
N,N’‐(3,6‐dinitropyrazole[4,3‐c] (25) was
pyrazole‐1,4‐diyl)dinitramine (25) obtained
was obtainedby filtering
by fil‐ the
reaction
tering thesolution
reactionand washing
solution andwith TFAA.
washing The
with synthesis
TFAA. The route is shown
synthesis route in Schemein14.
is shown
Scheme 14.
Scheme 14. Synthesis of N,N’‐ (3,6‐dinitropyrazole [4,3‐c] pyrazole‐1,4‐diyl) dinitramine [27].

2.2.4. Nitrification of ‐NH2 Connected with the Pyrazole Ring N
Scheme 13. Synthesis of 4,4′,5,5′‐tetranitro‐2H,2′H‐3,3′‐bipyrazole [26].
A fuming HNO3/con. H2SO4 system can be used to nitrate –NH2 to NHNO2, which is
2.2.4. Nitrification
connected with of
N‐NH
in a2 Connected with the Pyrazole Ring N
pyrazole ring.
AYin et al.
fuming HNO[27] cooled
3/con. H2SOa4 system
concentrated H2to
can be used SOnitrate
4 suspension of 3,6‐dinitropyrazole[4,3‐c]
–NH2 to NHNO 2, which is
connected with N in a pyrazole

pyrazole‐1,4‐diamine (24) ring.
to −15°C in an ice‐salt bath, then fuming HNO3 was added
Yin et al. [27] cooled a concentrated H2SO4 suspension of 3,6‐dinitropyrazole[4,3‐c]
dropwise to the mixture. After the mixture was stirred for 2 h at −15 °C,
pyrazole‐1,4‐diamine (24) to −15°C in an ice‐salt bath, then fuming HNO3 was added
N,N’‐(3,6‐dinitropyrazole[4,3‐c]
dropwise to the mixture. After the pyrazole‐1,4‐diyl)dinitramine
mixture was stirred for 2 h (25) at −15was°C,obtained by fil‐
Molecules 2022, 27, 1465 N,N’‐(3,6‐dinitropyrazole[4,3‐c] pyrazole‐1,4‐diyl)dinitramine (25) was obtained by fil‐7 of is
tering the reaction solution and washing with TFAA. The synthesis route 20 shown in
Scheme 14.
tering the reaction solution and washing with TFAA. The synthesis route is shown in
Scheme 14.
Scheme 14. Synthesis of N,N’‐ (3,6‐dinitropyrazole [4,3‐c] pyrazole‐1,4‐diyl) dinitramine [27].

0 -(3,6-dinitropyrazole [4,3-c] pyrazole-1,4-diyl) dinitramine [27].
Scheme 14.Synthesis
Scheme14. Synthesisof N,N
of N,N’‐ (3,6‐dinitropyrazole [4,3‐c] pyrazole‐1,4‐diyl) dinitramine [27].
2.3. Triazoles
2.3. Triazoles
2.3.
2.3.1.Triazoles
2.3.1. NitrificationofofHHon
Nitrification on1,2,4‐Triazole
1,2,4-Triazole Ring
Ring CC
2.3.1.70%
(1) Nitrification
HNO3 systemof H on 1,2,4‐Triazole Ring C
(1) 70% HNO3 system
3-nitro-1,2,4-triazol-5-one (NTO) is is a kind of insensitive high-energy explosive
with with
(1) 3‐nitro‐1,2,4‐triazol‐5‐one
70%comprehensive
excellent HNO3 systemperformance (NTO) a kind of insensitive high‐energy explosive
excellent comprehensive performance [28,29]. The more mature synthesis method of of
[28,29]. The more mature synthesis method
NTO is by
by nitration
nitrationof ofTO(1,2,4‐triazol‐5‐one),
NTO 3‐nitro‐1,2,4‐triazol‐5‐one
is TO(1,2,4-triazol-5-one),
(NTO) iswhich a which
kind is synthesized
of insensitive
is synthesized fromfrom semicarbazide
high‐energy
semicarbazide explosive with
hydrochloride
excellent
hydrochloride and formic
formicacid
comprehensive
and acidperformance
usingcondensation
using condensation[28,29].
andand cyclization
The
cyclizationmore reaction.
mature
reaction. TheThe synthesismethod of
synthesis
synthe‐
route is shown
sis route in Scheme 15.15.
The nitrating
nitratingagent
agentisis70% oror98% HNO
HNO33.. Huang
Huang et etal.
al. [30]
NTO is is
byshown in Scheme
nitration The
of TO(1,2,4‐triazol‐5‐one), 70%
which 98%
is synthesized from semicarbazide
added TO to 70%
[30] added TO to 70% HNO HNO 3 3 in batches at 60–65 °C, reacted for 1 h, then cooled to 3 °C inin an
in batches at 60–65 C, reacted for 1 h, then cooled to 3 C
hydrochloride
ice-water bath, and
filtered,formic
and acid
collected using condensation and cyclization reaction. The synthe‐
an ice‐water bath, filtered, and collectedthe theHNO
HNO 3 3filtrate,
filtrate,which
which waswas recycled
recycled in in the
the next
sis
batchroute is shown
of reactions.
next batch Thein
of reactions.
Scheme
filter cake cake
The filter
15.rinsed
was The nitrating
with with
was rinsed
agent
waterwater is 70% by
and followed
and followed
or vacuum
98% HNO
by vacuum
3. Huang et al.
filtration.
Finally,
[30] added
filtration.NTO wasto
TO
Finally, obtained
NTO70%was HNOvia 3recrystallization
obtainedin batches at 60–65
via recrystallization °C,from
from water with
reacted
watera for
yield
with of
1 h,
a then
yield ofand a to 3 °C in
75.4%cooled
purity
an
75.4% of
and99.94%.
ice‐water Compared
bath,
a purity with
of filtered,
99.94%. the use
and
Compared ofwith
collected98%theHNO
theuseHNO3 as
of the
98% nitrating
3 filtrate,
HNO3 as agent,
which this
was nitration
the nitrating recycled in the
method
agent, has
this a simpler
nitration process,
method hassafer
a operation,
simpler and
process, HNO
safer
next batch of reactions. The filter cake was rinsed with water and followed 3 filtrate
operation, canandbe reused,
HNO so the
3 filtrate cost
by vacuum
of
canraw materials
be reused, cancost
so the be lowered.
of raw materials can be lowered.
filtration. Finally, NTO was obtained via recrystallization from water with a yield of
75.4% and a purity of 99.94%. Compared with the use of 98% HNO3 as the nitrating
agent, this nitration method has a simpler process, safer operation, and HNO3 filtrate
can be reused, so the cost of raw materials can be lowered.

Scheme Synthesisofof3‐nitro‐1,2,4‐triazol‐5‐one
15. Synthesis
Scheme 15. 3-nitro-1,2,4-triazol-5-one [30].
[30].
(2) HNO3 /Ac2 O system

Aizikovich et al. [31] added 99% HNO to Ac O at 0 C while stirring for 30 min. The
Aizikovich et al. [31] added 99% HNO33 to Ac22O at 0 °C while stirring for 30 min.
solid N3 ,N6 -bis(1H-1,2,4-triazol-5-yl)-1,2,4,5-tetrazine-3,6-diamine (26) was slowly added to
The solid N3,N6‐bis(1H‐1,2,4‐triazol‐5‐yl)‐1,2,4,5‐tetrazine‐3,6‐diamine (26) was slowly
the mixture,
Scheme after which, the solution was stirred for 2 h under anhydrous conditions. Then,
added to 15.
the Synthesis of 3‐nitro‐1,2,4‐triazol‐5‐one
mixture, after which, the solution was stirred [30].for 2 h under anhydrous con‐
the reaction solution was warmed to room temperature, filtered and
ditions. Then, the reaction solution was warmed to room temperature, filtered and
washed quickly with
TFAA,
washedand immediately
quickly with TFAA, redissolved in hot CH
and immediately 3 CN. Theinobtained
redissolved CH3The
hot CH3CN. CN obtained
solution was
heated for 30 min at 65 C, then cooled to room temperature. Pure N 3 ,N 6 -bis(3-nitro-1H-
CH3CN solution was heated for 30 min at 65 °C, then cooled to room temperature. Pure
1,2,4-triazole-5-yl)-1,2,4,5-tetrazine-3,6-diamine (28) was filtrated and
N3,N6‐bis(3‐nitro‐1H‐1,2,4‐triazole‐5‐yl)‐1,2,4,5‐tetrazine‐3,6‐diamine washed
(28) was with CH3 CN
filtrated
to give a yield of 31%. The synthesis route is shown in Scheme 16. Although
and washed with CH3CN to give a yield of 31%. The synthesis route is shown in Scheme the yield of
the
16. Although the yield of the reaction is low, the operation is simple with short reaction does
reaction is low, the operation is simple with short reaction time, and the product
not
time,need
and further purification.
the product does not need further purification.
Scheme SynthesisofofNN
16. Synthesis 3 ,N 6 -Bis(3-nitro-1H-1,2,4-triazol-5-yl)-1,2,4,5-tetrazine-3,6-diamine [31].
Scheme 16. 3,N 6‐Bis(3‐nitro‐1H‐1,2,4‐triazol‐5‐yl)‐1,2,4,5‐tetrazine‐3,6‐diamine [31].
2.3.2. Nitrationofof‐NH
2.3.2. Nitration -NH onon
22
1,2,4-Triazole
1,2,4‐triazole ringRing
C C
(1) HNO3 /concentrated H2 SO4 system
(1) HNO3/concentrated H2SO4 system
From the synthetic method by Astachov et al. [32], Dippold et al. [33] synthesized
From the synthetic
3,30 -diamino-5,5 method by Astachov
0 -bis (1H-1,2,4-triazole) et al. [32],
(DABT,29) Dippold et al. reaction
via condensation [33] synthesized
using oxalic
3,3′‐diamino‐5,5′‐bis (1H‐1,2,4‐triazole) (DABT,29) via condensation reaction using oxalic
acid and aminoguanidine bicarbonate as raw materials. After that, HNO3 was slowly
added to a concentrated H2SO4 solution of compound 29 at 0 °C. The mixture was
warmed to room temperature and stirred for 1 h. The clear solution was then poured
onto ice and the precipitate was collected by filtration. A yellow crystalline solid of
3,3′‐dinitramine‐5,5′‐bis (1H‐1,2,4‐triazole) (DNABT, 30) was obtained by recrystalliza‐
tion from boiling water with a yield of 77%. The synthesis route is shown in Scheme 17.
Scheme 16. Synthesis of N3,N6‐Bis(3‐nitro‐1H‐1,2,4‐triazol‐5‐yl)‐1,2,4,5‐tetrazine‐3,6‐diamine [31].
2.3.2.
Scheme Nitration of ‐NH
16. Synthesis 2 on
of N 3,N61,2,4‐triazole ring C
‐Bis(3‐nitro‐1H‐1,2,4‐triazol‐5‐yl)‐1,2,4,5‐tetrazine‐3,6‐diamine [31].
(1)
2.3.2.HNO 3/concentrated H2SO4 system
Nitration of ‐NH2 on 1,2,4‐triazole ring C
From the synthetic method by Astachov et al. [32], Dippold et al. [33] synthesized
3,3′‐diamino‐5,5′‐bis
(1) HNO3/concentrated (1H‐1,2,4‐triazole)
H2SO4 system(DABT,29) via condensation reaction using oxalic
Molecules 2022, 27, 1465 acid From
and aminoguanidine
the synthetic method bicarbonate as raw etmaterials.
by Astachov After that,
al. [32], Dippold HNO
et al. was
of 20 slowly
[33]3 8synthesized
added to a concentrated H 2SO4 solution of compound 29 at 0 °C. The mixture was
3,3′‐diamino‐5,5′‐bis (1H‐1,2,4‐triazole) (DABT,29) via condensation reaction using oxalic
warmed
acid andtoaminoguanidine
room temperature and stirred
bicarbonate for 1materials.
as raw h. The clear solution
After was 3then
that, HNO waspoured
slowly
acid
onto
addedand
icetoaminoguanidine
and
a concentrated bicarbonate
the precipitate H2SO was as raw of
collected
4 solution materials.
bycompound After29
filtration. Athat,
at HNO
yellow was slowly
0 °C.crystalline
3 The mixturesolidwas
of
added to a concentrated
3,3′‐dinitramine‐5,5′‐bis H 2 SO solution of
(1H‐1,2,4‐triazole)
4 compound
(DNABT,29 at 0 C.
30) The
was mixture
obtained
warmed to room temperature and stirred for 1 h. The clear solution was then poured wasby warmed
recrystalliza‐
to room
tion
onto fromtemperature
ice boiling
and and stirred
thewater with afor
precipitate 1 h. collected
yield
was The clearThe
of 77%. solution was then
by synthesis
filtration. Apoured
route onto
is shown
yellow ice
inand thesolid
Scheme
crystalline 17.of
precipitate was collected by filtration. A yellow crystalline solid of 3,30 -dinitramine-5,50 -bis
3,3′‐dinitramine‐5,5′‐bis (1H‐1,2,4‐triazole) (DNABT, 30) was obtained by recrystalliza‐
(1H-1,2,4-triazole) (DNABT, 30) was obtained by recrystallization from boiling water with
tion from boiling water with a yield of 77%. The synthesis route is shown in Scheme 17.
a yield of 77%. The synthesis route is shown in Scheme 17.
Scheme 17. Synthesis of 3,3′‐dinitrimino‐5,5′‐bis(1H‐1,2,4‐triazole) [33].
(1) HNO
Scheme
Scheme 17. 3/P2O5 system
17.Synthesis
Synthesisof of 0 -dinitrimino-5,50 -bis(1H-1,2,4-triazole) [33].
3,33,3′‐dinitrimino‐5,5′‐bis(1H‐1,2,4‐triazole) [33].
Wang et al. [21] dissolved P2O5 in fuming HNO3, then
(2)
(1) HNO
HNO33/P O5 system
/P22O
(6‐(3,5‐dimethyl‐1H‐pyrazol‐1‐yl)‐1,2,4‐
5 system triazole[4,3‐b]‐1,2,4,5‐tetrazine‐3‐amino (31) was
added Wang
Wang et al.
to the [21]
et dissolved
mixture at 0 °C
al. Pand
[21]2 O5 in fuming
stirred at HNO
dissolved room3P,temperature
then (6-(3,5-dimethyl-1H-pyrazol-1-
2O5 in for 10 h. Then,
fuming HNO the3, mixture
then
yl)-1,2,4-
was triazole[4,3-b]-1,2,4,5-tetrazine-3-amino
poured onto crushed ice and (31) was
extracted added
with to the
ethyl mixture at
acetate, 0 C and which,
after
(6‐(3,5‐dimethyl‐1H‐pyrazol‐1‐yl)‐1,2,4‐ triazole[4,3‐b]‐1,2,4,5‐tetrazine‐3‐amino (31) was
stirred at room temperature for 10 h. Then, the mixture was poured onto crushed ice and
N‐(6‐(3,5‐dimethyl‐4‐nitro‐1H‐pyrazol‐1‐yl)‐1,2,4‐triazole[4,3‐b]‐1,2,4,5‐tetrazin‐3‐yl) ni‐
added to the mixture at 0 °C and stirred at room temperature for 10 h. Then, the mixture
extracted with ethyl acetate, after which, N-(6-(3,5-dimethyl-4-nitro-1H-pyrazol-1-yl)-1,2,4-
tramine (32) was purified
was poured onto crushed nitramineby column chromatography
ice and (32)extracted with a yield
withby ethyl of 58%. The synthesis
triazole[4,3-b]-1,2,4,5-tetrazin-3-yl) was purified column acetate, after which,
chromatography
route is shown in Scheme 18. The nitrating reagents used in this reaction are relatively
N‐(6‐(3,5‐dimethyl‐4‐nitro‐1H‐pyrazol‐1‐yl)‐1,2,4‐triazole[4,3‐b]‐1,2,4,5‐tetrazin‐3‐yl) ni‐
with a yield of 58%. The synthesis route is shown in Scheme 18. The nitrating reagents
mild,
traminebut the
(32) post‐treatment
was purified by is relatively
column complicated.
used in this reaction are relatively mild, but the post-treatment is relatively complicated.
chromatography with a yield of 58%. The synthesis
route is shown in Scheme 18. The nitrating reagents used in this reaction are relatively
mild, but the post‐treatment is relatively complicated.
Scheme
18. of
2.3.3. Nitrification ofN-(6-(3,5-dimethyl-4-nitro-1H-pyrazol-1-yl)
H Synthesis
on 1,2,4‐Triazole -1,2,4-triazolo[4,3-b]-1,2,4,5-
of Ring NN‐(6‐(3,5‐dimethyl‐4‐nitro‐1H‐pyrazol‐1‐yl)
tetrazin-3-yl)nitramide [21].
‐1,2,4‐triazolo[4,3‐b]‐1,2,4,5‐tetrazin‐3‐yl)nitramide [21].
(1)
2.3.3.
SchemeHNO 3/Ac18.
2O
Nitrification ofsystem
H on 1,2,4-Triazole
Synthesis RingofN N‐(6‐(3,5‐dimethyl‐4‐nitro‐1H‐pyrazol‐1‐yl)
‐1,2,4‐triazolo[4,3‐b]‐1,2,4,5‐tetrazin‐3‐yl)nitramide
(1) HNO
Yin et/Ac O system
al. [34] [21].
dissolved TFAA and 3‐nitro‐1,2,4‐triazole in chloroform at 0~5 °C, and
3 2
fuming HNO
Yin et 3 was
al. [34] addedTFAA
dissolved dropwise while maintaining
and 3-nitro-1,2,4-triazole the temperature.
in chloroform at 0~5 C, After
and the drop‐
wise addition
fuming HNO3 was was completed,
added dropwise the reaction
while was the
maintaining warmed and stirred
temperature. fordropwise
After the 1 h at room tem‐
addition
perature. was The
completed, the reaction
reaction was warmed
solution was and thenstirred for 1 h atonto
poured room temperature.
crushed ice, and
The reaction solution was then poured onto crushed ice, and 1,3-dinitro-1H-1,2,4-triazole
1,3‐dinitro‐1H‐1,2,4‐triazole (33) was obtained by extraction with chloroform with a
(33)
yieldwasofobtained
53%. The by synthesis
extraction with
routechloroform
is shownwith a yield of19.
in Scheme 53%. The synthesis route is
shown in Scheme 19.
Scheme 19.Synthesis
Scheme19. Synthesisof 1,3-dinitro-1H-1,2,4-triazole [34]. [34].
of 1,3‐dinitro‐1H‐1,2,4‐triazole
2.3.4. Nitrification of -NH2 on 1,2,4-Triazole Ring N
2.3.4. Nitrification of ‐NH2 on 1,2,4‐Triazole Ring N
(1) HNO3 system
(1) Klapçtke et al. [35] synthesized 4,40 ,5,50 -tetraamino-3,30 -bi-1,2,4-triazole (34) using
HNO3 system
oxalic acid and diaminoguanidine hydrochloride as raw materials via a condensation
Klapçtke
reaction et al.
under the [35]ofsynthesized
action polyphosphoric 4,4′,5,5′‐tetraamino‐3,3′‐bi‐1,2,4‐triazole
acid. HNO3 was cooled to 10 C and (34) using
compound 1 was slowly added while the temperature was
oxalic acid and diaminoguanidine hydrochloride as kept
rawbelow 0 C. After
materials via a that,
condensation
the mixture was stirred for 90 min at 5 C. Then, the solution was poured onto
reaction under the action of polyphosphoric acid. HNO3 was cooled to −10 °C and com‐ crushed
ice, stirred for 10–15 min,added
filtered, and 5,5 0 0 -dinitroammonium-3,30 -di-(1,2,4-
pound 1 was slowly while the-diamino-4,4
temperature was kept below 0 °C. After that, the
triazole) (35) was obtained by washing with cold water, ethanol, and ether, respectively,
mixture was stirred for 90 min at −5 °C. Then, the solution was poured onto crushed ice,
stirred for 10–15 min, filtered, and
5,5′‐diamino‐4,4′‐dinitroammonium‐3,3′‐di‐(1,2,4‐triazole) (35) was obtained by washing
with cold water, ethanol, and ether, respectively, with a yield of 69%. The synthesis
route is shown in Scheme 20. The synthetic method is simple in operation, and the ob‐
tained product does not require further purification.
reaction under the action of polyphosphoric acid. HNO3 was cooled to −10 °C and com‐
pound 1 was slowly added while the temperature was kept below 0 °C. After that, the
mixture was stirred for 90 min at −5 °C. Then, the solution was poured onto crushed ice,
stirred for 10–15 min, filtered, and
5,5′‐diamino‐4,4′‐dinitroammonium‐3,3′‐di‐(1,2,4‐triazole) (35) was obtained by washing
with cold water, ethanol, and ether, respectively, with a yield of 69%. The synthesis
route is shown in Scheme 20. The synthetic method is simple in operation, and the ob‐
Molecules 2022, 27, 1465 tained product does not require further purification. 9 of 20
with a yield of 69%. The synthesis route is shown in Scheme 20. The synthetic method is
simple in operation, and the obtained product does not require further purification.
Scheme 20. Synthesis of 5,5′‐diamino‐4,4′‐dinitramino‐3,3′‐bi‐1,2,4‐triazole [35].
Scheme 20. Synthesis of 5,50 -diamino-4,40 -dinitramino-3,30 -bi-1,2,4-triazole [35].

2.3.5. Nitration of ‐NH2 Connected with 1,2,3‐Triazole Ring C
2.3.5. Zhang
Nitration
etofal.-NH 2 Connected
[36] with 1,2,3-Triazole Ring C
added 4‐amino‐5‐nitro‐1,2,3‐2H‐triazole (36) to a mixture of HNO3
(70%) Zhang
and et al. [36] addedH4-amino-5-nitro-1,2,3-2H-triazole
concentrated 2SO4 in batches and stirred for (36)
2 htoata mixture of HNO
0 °C. After stirring
3 for an‐
(70%) and concentrated H 2 SO 4 in batches and stirred for 2 h at 0 C.
other 2 h at room temperature, the reaction mixture was poured into ice water. After stirring for
another 2 h at room temperature, the reaction mixture was poured into ice water. 4-
4‐nitramine‐5‐nitro‐1,2,3‐2H‐ triazole (37) was obtained by ether extraction, and the yield
nitramine-5-nitro-1,2,3-2H-triazole (37) was obtained by ether extraction, and the yield was
was 76%. The synthesis route is shown in Scheme 21.
76%. The synthesis route is shown in Scheme 21.
2.3.6.
Scheme
Scheme Nitrification
21.Synthesis
21. Synthesisofof4-nitramino-5-nitro-1,2,3-2H-triazole
ofH4‐nitramino‐5‐nitro‐1,2,3‐2H‐triazole
on 1,2,3‐Triazole Ring N [36]. [36].
2.3.6. Thottempudi
Nitrification of Het on
al.1,2,3-Triazole
[37] added Ringconcentrated
N HNO3 to Ac2O dropwise at −5 °C, the
mixture
Thottempudi et al. [37] added concentrated HNO3 toanother
was stirred for 30 min, and then stirred for 45 min at
Ac2 O dropwise at room temperature.
5 C, the
Subsequently,
mixture was stirred the for
mixture
30 min,wasand cooled to −5for°C,
then stirred and tris(triazolo)
another 45 min at roombenzene (38) was add‐
temperature.
Subsequently,
ed in portions, thestirred
mixturefor
wasabout
cooled15to min,
5 C, andstirred
and tris(triazolo) benzene
overnight at (38)
room was added
temperature. The
in portions,
mixture was stirred
thenfor about 15
poured min,
onto and
ice, stirred and
filtered, overnight
washed at room
withtemperature. The the final
water to obtain
mixture was
product then poured onto ice, filtered, and
of trinitrotris(triazolo)benzene (39) washed
with a with
yieldwater to obtain
of 53%. the final route is
The synthesis
product of trinitrotris(triazolo)benzene (39) with a yield of 53%. The synthesis route is
shown in Scheme 22.
shown in Scheme 22.
22.Synthesis
Scheme 22.
Scheme Synthesisof 2,5,8-trinitrotris(triazolo)benzene [37]. [37].
of 2,5,8‐trinitrotris(triazolo)benzene
2.4. Tetrazoles
2.4.
2.4.1.Tetrazoles
Nitrification of -NH2 on Tetrazole C
2.4.1.NO
(1) Nitrification
2 BF4 systemof ‐NH2 on Tetrazole C
Stierstorfer et al. [38] dissolved 1-(2-azidoethyl)-5-aminotetrazole (40) in MeCN in

(1) NO2BFbath,
an ice-water 4 system
and added nitronium tetrafluoroborate (NO2 BF4 ) to the solution. The
solution was then stirred
Stierstorfer for 30dissolved
et al. [38] min at 0 C1‐(2‐azidoethyl)‐5‐aminotetrazole
and for another 1 h at 25 C. The solvent
(40)was
in MeCN in
evaporated
an ice‐waterand KOHand
bath, ethanol
addedsolution was added.
nitronium The precipitated
tetrafluoroborate KBF
(NO 4 was
2BF
removed
4) to the solution. The
by filtration and another equivalent of KOH in ethanol was added. The solvent was
solution was then stirred for 30 min at 0 °C and for another 1 h at 25 °C. The solvent was
evaporated and cold water was added. The insoluble material was removed by filtration
evaporated
and the waterand
was KOH ethanol
evaporated. solution
Potassium was added. The precipitated KBF
1-(2-azidoethyl)-5-nitroaminotetrazole (41)4 was
was removed
evaporated and cold water was added. The insoluble material was removed by filtration
and the water was evaporated. Potassium 1‐(2‐azidoethyl)‐5‐nitroaminotetrazole (41)
was finally obtained by recrystallization from hot ethanol with a yield of 33%. After that,
an equimolar amount of dilute (1N) HCl was added to compound 41. Then, the solvent
was evaporated and acetone was added to the residue. The solution was filtered to re‐
(1) NO2BF4 system
Stierstorfer et al. [38] dissolved 1‐(2‐azidoethyl)‐5‐aminotetrazole (40) in MeCN in
an ice‐water bath, and added nitronium tetrafluoroborate (NO2BF4) to the solution. The
solution was then stirred for 30 min at 0 °C and for another 1 h at 25 °C. The solvent was
evaporated and KOH ethanol solution was added. The precipitated KBF4 was removed
Molecules 2022, 27, 1465 evaporated and cold water was added. The insoluble material was removed10byof filtration 20
and the water was evaporated. Potassium 1‐(2‐azidoethyl)‐5‐nitroaminotetrazole (41)

was finally obtained by recrystallization from hot ethanol with a yield of 33%. After that,
finally obtainedamount
an equimolar by recrystallization from
of dilute (1N) hotwas
HCl ethanol withtoa compound
added yield of 33%.41.After that,
Then, theansolvent
equimolar amount of dilute (1N) HCl was added to compound 41. Then, the
was evaporated and acetone was added to the residue. The solution was filtered to re‐ solvent was
evaporated
move KCl. and acetone
After acetonewaswasadded to the residue.
evaporated, The solution
the crude product was filtered
was to removefrom a
recrystallized
KCl. After acetone was evaporated, the crude product was recrystallized from a small
small amount of methanol to yield colorless 42 (90%). The synthesis route is shown in
amount of methanol to yield colorless 42 (90%). The synthesis route is shown in Scheme 23.
Scheme 23. The reaction conditions are mild and the temperature is easy to control.
The reaction conditions are mild and the temperature is easy to control. However, HBF4
However, HBF4 must
must be removed be removed
after the after
reaction, the theofreaction,
yield compoundthe41 yield of and
is low, compound 41 is low, and
the purification
the
is purification is difficult.
difficult.
N N NO2 N NO2
N N HCl N
NH2 NO2BF4 N N
N N N N N N H
K
N3 N3 N3
40 41 42
Scheme 23.Synthesis
Scheme23. Synthesisofof
1-(2-azidoethyl)-5-nitriminotetrazole [38]. [38].
1‐(2‐azidoethyl)‐5‐nitriminotetrazole
(2) N O system
(2) N22O55 system
Fischer et al. [39] synthesized 1-methoxycarbonyl-1,5-diaminotetrazole (43) using
Fischer et al. [39] synthesized 1‐methoxycarbonyl‐1,5‐diaminotetrazole (43) using
dimethyl carbonate via nucleophilic substitution and a ring formation reaction. After that,
dimethyl carbonate via nucleophilic substitution and a ring formation reaction. After
compound 43 was suspended in anhydrous acetonitrile at 0 C, a solution of N2 O5 in
that, compound
acetonitrile (MeCN) 43was
was suspended
added, and the in anhydrous
mixture acetonitrile
was stirred at 0 aqueous
for 1 h. KOH °C, a solution
solutionof N2O5
Molecules 2022, 27, x FOR PEER REVIEW
in acetonitrile (MeCN) was added, and the mixture was stirred for
was then added dropwise, the aqueous phase was separated, and the water was evaporated 1 h. KOH 11 of 20
aqueous
under
solutionhigh
wasvacuum. The residue
then added was stirred
dropwise, in methanol
the aqueous phasefor several
was hours. and
separated, The reaction
the water was
solution
evaporatedwas filtered,
under highwashed with methanol,
vacuum. and dried.
The residue The obtained
was stirred solid was
in methanol fordissolved
several hours.
in
The 2Mreaction
tion HCl,ethyl
with and 1,5-bis(nitroamino)tetrazole
solution
acetatewas
in afiltered,
yield ofwashed
50%. The(46)
withwas obtained
methanol,
synthesis routebyisextraction
and dried.
shownThe inwith ethyl24.solid
obtained
Scheme The
acetate
was in a yieldin
dissolved of 2M
50%.HCl,
The synthesis
and route is shown in Scheme 24.
1,5‐bis(nitroamino)tetrazole The
(46) wasreaction
obtainedhas less
by extrac‐
reaction has less heat generation and the temperature is easy to control. Moreover, the
heat generation and the temperature is easy to control. Moreover, the product separation is
product separation is simple
simple with no waste acid treatment.
with no waste acid treatment.
Scheme 24.Synthesis
Scheme24. Synthesisof of
1,5-di(nitramino)tetrazole [39]. [39].
1,5‐di(nitramino)tetrazole
(3) 100% HNO system

3
(3) 100% HNO 3 system
Kumar et al. [40] synthesized amino 1-((1H-tetrazol-5-yl)methyl)-1H-tetrazole-5-amino
Kumar et al. [40] synthesized amino
(48) using aminoacetonitrile hydrochloride and cyanide azide (47) as raw materials through
1‐((1H‐tetrazol‐5‐yl)methyl)‐1H‐tetrazole‐5‐amino
two-step ring formation reaction. Then, compound 2 was (48)slowly
usingadded
aminoacetonitrile
to 100% HNO3 hydro‐
chloride and cyanide azide (47) as raw materials through two‐step
at 0–2 C. After stirring for 12 h at room temperature, the mixture was poured ring formation
into cold reac‐
tion. Then, compound 2 was slowly added to 100% HNO at 0–2 °C. After
water. Thus, N-(1-((1H-tetrazol-5-yl)methyl)-1H-tetrazole-5 (4H)-alkylene)nitramine
3 stirring
(49) for 12
was
h atobtained
roomby temperature,
extraction with the
ethyl mixture
acetate in awas
yieldpoured
of 65%. The
intosynthesis
cold route
water.is Thus,
shown in Scheme 25.
N‐(1‐((1H‐tetrazol‐5‐yl)methyl)‐1H‐tetrazole‐5 (4H)‐alkylene)nitramine (49) was ob‐
tained by extraction with ethyl acetate in a yield of 65%. The synthesis route is shown in
Scheme 25.
Kumar et al. [40] synthesized amino
1‐((1H‐tetrazol‐5‐yl)methyl)‐1H‐tetrazole‐5‐amino (48) using aminoacetonitrile hydro‐
chloride and cyanide azide (47) as raw materials through two‐step ring formation reac‐
tion. Then, compound 2 was slowly added to 100% HNO3 at 0–2 °C. After stirring for 12
h at room temperature, the mixture was poured into cold water. Thus,
N‐(1‐((1H‐tetrazol‐5‐yl)methyl)‐1H‐tetrazole‐5 (4H)‐alkylene)nitramine (49) was ob‐
Molecules 2022, 27, 1465 tained by extraction with ethyl acetate in a yield of 65%. The synthesis route11isofshown
20 in
Scheme 25.
Scheme 25.Synthesis
Scheme25. Synthesisof of
N-(1-((1H-tetrazol-5-yl)methyl)-1H-tetrazol-5(4H)-ylidene)nitramide [40].
N‐(1‐((1H‐tetrazol‐5‐yl)methyl)‐1H‐tetrazol‐5(4H)‐ylidene)nitramide [40].
2.4.2. Nitrification of -NH2 Connected with Tetrazole Ring N
2.4.2. Nitrification of ‐NH2 Connected with Tetrazole Ring N
(1) NO2 BF4 system
(1) Klapçtke
NO2BF4 et al. [41] dissolved 1,5-diaminotetrazole in anhydrous acetonitrile at 0 C and
system
added NO2 BF4 to the solution with stirring. The reaction mixture was then stirred overnight
Klapçtke et al. [41] dissolved 1,5‐diaminotetrazole in anhydrous acetonitrile at 0 °C
at room temperature. A pale yellow solid was obtained by evaporating acetonitrile under
vacuum. The NO
and added solid2BF was4 to the solution with stirring. The reaction mixture was then stirred
re-dissolved in a small amount of ethanol, and then a mixed solution
overnight at room
of KOH and ethanol was temperature. A pale yellow
added to precipitate solidtetrafluoroborate.
potassium was obtained byFollowed
evaporating
by ace‐
tonitrile under
filtration, the filtratevacuum. The solidand
was evaporated was re‐dissolved in a small amount
5-amino-1-nitroaminotetrazole (HDATNOof ethanol,
2 , 50)
and
was
thenobtained
Molecules 2022, 27, x FOR PEER REVIEW a mixed with a yield of
solution of 59%.
KOHThe andsynthesis
ethanol route
wasis added
shown in toScheme 26. The
precipitate nitrating tetra‐
potassium 12 of 20
Molecules 2022, 27, x FOR PEER REVIEW agent, NO
fluoroborate.
2 BF 4 , is environmentally
Followed by friendly and
filtration, does not
the require waste
filtrate acid
was treatment.
evaporatedThe and
reaction conditions are mild and the
5‐amino‐1‐nitroaminotetrazole temperature
(HDATNO is easy
2, 50) was to control. with
obtained Thereaare fewer
yield of by-
59%. The
products in the reaction and the selectivity of the reaction is high, but NO
synthesis route is shown in Scheme 26. The nitrating agent, NO2BF4, is environmentally 2 BF4 is expensive
and has high
friendly andcosts.
does not require waste acid treatment. The reaction conditions are mild and
the temperature is easy to control. There are fewer by‐products in the reaction and the
selectivity of the reaction is high, but NO2BF4 is expensive and has high costs.
Scheme 26. Synthesis of 5‐amino‐1‐nitriminotetrazole [41].
(2) N226.
Scheme O5Synthesis
system of 5-amino-1-nitriminotetrazole [41].
Scheme 26. Synthesis of 5‐amino‐1‐nitriminotetrazole [41].
Fischer et al. [42] suspended 1,1′‐diamino‐5,5′‐azobitetrazole (51) in dry acetonitrile
(2) N2 O5 system
at 0 °C and added a solution of0 N2O5 in cold acetonitrile dropwise. The KOH solution
(2) Fischer
N2O5etsystem al. [42] suspended 1,1 -diamino-5,50 -azobitetrazole (51) in dry acetonitrile
was added dropwise until 1,1′‐diamino‐5,5′‐azobitetrazole was dissolved, and then the
at 0 C and added a solution of N2 O5 in cold acetonitrile dropwise. The KOH solution
red added
was
Fischer
crystal of et
dropwise
al. [42] suspended 1,1′‐diamino‐5,5′‐azobitetrazole
1,1′‐dinitroammonium‐5,5′‐azobitetrazole dipotassium
until 1,10 -diamino-5,50 -azobitetrazole was dissolved, and thensalt
(51)
(52)
the red
in ob‐
was dry
at 0 °C
tained
crystal ofviaand
1,1 addedThe
filtration. a solution
yield was
0 -dinitroammonium-5,5 of N2O
62%. 5 in cold acetonitrile
Subsequently,
0 -azobitetrazole dipotassium the
saltsalt
(52)4was dropwise.
was dissolvedThe
obtained in 2MKO
via
HCl,filtration.
and a The yield
colorless was 62%.
single Subsequently,
crystal of the salt 4 was dissolved in 2M
1,1′‐dinitroammonium‐5,5′‐azotetrazole
was added dropwise 0 until 1,1′‐diamino‐5,5′‐azobitetrazole HCl, and a (53)
was dissolved, anwas
colorless
obtainedsingle crystal of 1,1
via extraction with ethyl acetate. The0 -azotetrazole
-dinitroammonium-5,5 (53) was
synthesis route obtainedinvia
is shown Scheme 27.
red crystal
extraction
of 1,1′‐dinitroammonium‐5,5′‐azobitetrazole
with uses
ethylN acetate.
dipotassium
The synthesis route is shown in Scheme 27. This reaction
salt (5
This reaction 2O5 as a nitration system, which has higher nitration selectivity, less
tained
uses
side N 2 Ovia
5 as a
reactions,
filtration. The yield
nitration system,
superior yield, and which haswasequipment
62%.nitration
lowerhigher
Subsequently, the
selectivity, less
requirements,
saltreac-
side
thereby
4 was disso
reducing the
tions, superior
HCl,of and yield, and
a colorless lower equipment requirements, thereby reducing the cost of the
cost the entire
entire process.
process. single crystal of 1,1′‐dinitroammonium‐5,5′‐azotetrazo
obtained via extraction with ethyl acetate. The synthesis route is shown in
This reaction uses N2O5 as a nitration system, which has higher nitration sele
side reactions, superior yield, and lower equipment requirements, thereby re
cost of the entire process.
0 -dinitramino-5,50 -azobitetrazole [42].
Scheme 27.Synthesis
Scheme27. Synthesisof 1,1
of 1,1′‐dinitramino‐5,5′‐azobitetrazole [42].
2.5. Oxadiazoles
2.5.1. Nitration of ‐NH2 on 1,2,4‐oxadiazole ring C
(1) 100%27.
Scheme HNO 3 system
Synthesis of 1,1′‐dinitramino‐5,5′‐azobitetrazole [42].
Tang et al. [43] slowly added 5,5′‐diamino‐3,3′‐azo‐1,2,4‐oxadiazole (54) to 100%
HNO 3 at −5 °C and then slowly raised the temperature to room temperature. The mix‐
2.5. Oxadiazoles
cost of the entire process.
Scheme 27. Synthesis of 1,1′‐dinitramino‐5,5′‐azobitetrazole [42].

Molecules 2022, 27, 1465 12 of 20
2.5. Oxadiazoles
2.5.1. Nitration of ‐NH2 on 1,2,4‐oxadiazole ring C
2.5. Oxadiazoles
(1)
2.5.1.100% HNO
Nitration of3 system
-NH2 on 1,2,4-Oxadiazole Ring C
Tang et al.
(1) 100% HNO3 system [43] slowly added 5,5′‐diamino‐3,3′‐azo‐1,2,4‐oxadiazole (54) to 100%
HNO3 at −5 °C and then slowly raised the temperature to room temperature. The mix‐
Tang et al. [43] slowly added 5,50 -diamino-3,30 -azo-1,2,4-oxadiazole (54) to 100% HNO3 at
ture was stirred overnight. 5,5′‐dinitroammonium‐3,3′‐azo‐1,2,4‐oxadiazole (55) was ob‐
5 C and then slowly raised the temperature to room temperature. The mixture was stirred
tained via filtration and washed with TFAA, with a yield of 75%. The synthesis route is
overnight. 5,50 -dinitroammonium-3,30 -azo-1,2,4-oxadiazole (55) was obtained via filtration
shown in Scheme 28. The reaction yield is high and the obtained product is pure without
and washed with TFAA, with a yield of 75%. The synthesis route is shown in Scheme 28. The
further
reaction purification.
yield is high and the obtained product is pure without further purification.
0 -dinitramino-3,30 -azo-1,2,4-oxadiazole [43].

28. Synthesis
Scheme 28.
Scheme Synthesisof
of5,5
5,5′‐dinitramino‐3,3′‐azo‐1,2,4‐oxadiazole [43].
(2)
(2) HNOHNO33/Ac
/Ac2O 2 Osystem
system
Tang
Tang etet al.
al.[44]
[44]synthesized
synthesized3-amino-5-N-ethoxychloroamido-1,2,4-oxadiazole
3‐amino‐5‐N‐ethoxychloroamido‐1,2,4‐oxadiazole hy-hy‐
drochloride (56)
drochloride (56)using
usingthethe
sodium
sodiumsaltsalt
of malononitrile and hydroxylamine
of malononitrile and hydroxylamine as raw materials
as raw ma‐
(Scheme 29) through
terials (Scheme 29) athrough
ring formation
a ring reaction
formationandreaction
substitution
and reaction. HNOreaction.
substitution 3 (100%) was
HNO3
slowly added
(100%) was to the acetic
slowly added anhydride
to the at 0anhydride
acetic C. Compoundat 0 56 was
°C. then added
Compound 56 to
wasthethen
mixture
added
andthe
to stirred for 1and
mixture h. Afterwards,
stirred for 1the
h. reaction solution
Afterwards, the was poured
reaction into ice
solution waswater. The pure
poured into ice
product
water. The of 3-amino-5-N-nitro-ethoxyformamido-1,2,4-oxadiazole
pure product of 3‐amino‐5‐N‐nitro‐ethoxyformamido‐1,2,4‐oxadiazole (57) was obtained via(57)
filtration and washing with cold water. The yield was 73%.
was obtained via filtration and washing with cold water. The yield was Subsequently, compound 57
73%. Subse‐
was treated with a solution of hydrazine in acetonitrile to obtain 3-amino-5-nitroamino-
ino‐1,2,4‐oxadiazole
quently, compound 57 monohydrate
was treated with (59) was obtained
a solution via acidification
of hydrazine in acetonitrile with concentrated
to obtain
1,2,4-oxadiazole hydrazine salt (58). 3-amino-5- nitroamino-1,2,4-oxadiazole monohydrate
3‐amino‐5‐nitroamino‐1,2,4‐oxadiazole
hydrochloric acid.
ino‐1,2,4‐oxadiazole monohydrate (59) was hydrazine
obtained via salt (58). with
acidification 3‐amino‐5‐
concentrated nitroam‐
(59) was obtained via acidification with concentrated hydrochloric acid.
hydrochloric acid.
Scheme 29. Synthesis of 3‐amino‐5‐nitramino‐1,2,4‐oxadiazole monohydrate [44].

Scheme 29.Synthesis
Scheme29. Synthesisof 3-amino-5-nitramino-1,2,4-oxadiazole monohydrate
of 3‐amino‐5‐nitramino‐1,2,4‐oxadiazole [44].
monohydrate [44].
2.5.2. Nitrification of ‐NH2 on 1,3,4‐Oxadiazole Ring C
2.5.2. Nitrification of -NH2 on 1,3,4-Oxadiazole Ring C
2.5.2. Nitrification of ‐NH2 on 1,3,4‐Oxadiazole Ring C
(1) 100%HNO
(1) 100% HNO3 3system
system
0 -diamino-5,50 -bis(1-3,4-oxadiazole) (60)
100%et
(1) Tobias et al.
HNO al.[45]
[45]synthesized
synthesizedintermediate
3 system
intermediate2,2
2,2′‐diamino‐5,5′‐bis(1‐3,4‐oxadiazole)
using oxalodiazide
(60) using andand
oxalodiazide BrCNBrCNas raw materials.
as raw Compound
materials. Compound was
60 60 wasadded to to
added 100%
100%HNO3
in
HNO 3Tobias
portions at et
in portions0 al.
C, [45]
at 0and synthesized
°C, the
and mixture wasintermediate
the mixture stirred
was 122,2′‐diamino‐5,5′‐bis(1‐3,4‐oxadiazole)
forfor
stirred h at
12 h atroom temperature. 2,20 -
roomtemperature.
2,2′‐dinitroamino‐5,5‐bi(1‐3,4‐oxadiazole)
dinitroamino-5,5-bi(1-3,4-oxadiazole)
(60) using oxalodiazide and BrCN(61) (61)
as waswasobtained
raw obtainedby
materials. byCompound
filteringand
filtering andwashing
60washing with to 100%
was added
with
water,water,
HNOmethanol, methanol,
3 in portions
and
and ether, ether, respectively,
at 0 respectively,
°C, and thewith with a yield
a yieldwas
mixture of
of 84%.84%. The synthesis
The synthesis
stirred atroute
for 12 hroute is temperature.
is shown
room
shown
in Schemein Scheme 30. In
30. In this this reaction,
reaction, 100% 100%
HNOHNO 3 is used as a nitrating agent, and the
2,2′‐dinitroamino‐5,5‐bi(1‐3,4‐oxadiazole) 3 is used
(61)aswas
a nitrating
obtained agent,
byand the yield
filtering is washing
and
yield is
greater greater
than 80%than 80%
with a with
high a high
purity purity
of the of the nitrated
nitrated product.
product.
with water, methanol, and ether, respectively, with a yield of 84%. The synthesis route is
shown in Scheme 30. In this reaction, 100% HNO3 is used as a nitrating agent, and the
yield is greater than 80% with a high purity of the nitrated product.

Scheme 30. 2,20 -dinitramino-5,5-bi(1-oxa-3,4-diazole)
Synthesisofof2,2′‐dinitramino‐5,5‐bi(1‐oxa‐3,4‐diazole) [45].[45].
2.5.3. Nitration of ‐NH2 Connected with 1,2,5‐Oxadiazole(Furazan) Ring C
(1) N2O4/100% HNO3 system

Scheme 30. Synthesis of 2,2′‐dinitramino‐5,5‐bi(1‐oxa‐3,4‐diazole) [45].
Sheremetev et al. [46] added 3‐amino‐4‐methylfurazan (62) to a mixture of 100%
HNO3 and 2% N2O4 at −5 °C, and stirred for 1 h. Then, the reaction mixture was heated
2.5.3. Nitration of ‐NH2 Connected with 1,2,5‐Oxadiazole(Furazan) Ring C
Scheme 30. Synthesis of 2,2′‐dinitramino‐5,5‐bi(1‐oxa‐3,4‐diazole) [45].
Molecules 2022, 27, 1465 2.5.3. Nitration of ‐NH2 Connected with 1,2,5‐Oxadiazole(Furazan)
13 ofRing
20 C
(1) N2O4/100% HNO3 system

2.5.3. Nitration of -NH2 Connected with 1,2,5-Oxadiazole(Furazan) Ring C
(1) NSheremetev et al. [46] added 3‐amino‐4‐methylfurazan (62) to a mixture
2 O4 /100% HNO3 system
HNO 3 and 2% N2O4 at −5 °C, and stirred for 1 h. Then, the reaction mixture wa
Sheremetev et al. [46] added 3-amino-4-methylfurazan (62) to a mixture of 100% HNO3
to 20
and 2% N °C
2 Oand
4 at poured onto for
5 C, and stirred ice.1 h.3‐nitroamino‐4‐methylfurazan
Then, the reaction mixture was heated(63)
to 20 was
C obtained
and poured onto ice. 3-nitroamino-4-methylfurazan (63) was obtained
traction with diethyl ether, washing with cold water, and drying with MgSO via extraction with
diethyl ether, washing with cold water, and drying with MgSO4 , with a yield of 40–45%.
yield of 40–45%. The synthesis route is shown in Scheme 31.
The synthesis route is shown in Scheme 31.
Scheme 31. Synthesis of 3-nitroamino-4 -methylfurazan with N2 O4 /100% HNO3 system [46].
Scheme 31. Synthesis of 3‐nitroamino‐4 ‐methylfurazan with N2O4/100% HNO3 system [4
(2) NO2 BF4 system
(2) Sheremetev
NO2BF4 system
et al. [46] also added 3-amino-4-methylfurazan (62) to a CH2 Cl2 suspen-
sion ofSheremetev
NO2 BF4 . The mixture was cooled
et al. [46] to 0 C, stirred
also added for 1 h, and then the temperature
3‐amino‐4‐methylfurazan (62) to a CH2Cl2
was slowly raised to 5 C. Subsequently, the reaction mixture was poured onto ice, and the
sion of NO 2BF4. The mixture was cooled to 0 °C, stirred for 1 h, and then the tem
resulting emulsion was extracted with diethyl ether to obtain 3-nitroamino-4-methylfurazan
wasin slowly
(63) raised
a 63% yield. to 5 °C.route
The synthesis Subsequently, the reaction
is shown in Scheme 32. mixture was poured onto
the resulting emulsion was extracted with diethyl ether to
3‐nitroamino‐4‐methylfurazan (63) in a 63% yield. The synthesis route is s
Scheme
Scheme 32. 32.
Synthesis of 3‐nitroamino‐4 –methylfurazan with NO2BF4 system [46].
Scheme
(3) 32.
100%
Scheme 32.Synthesis
HNO of 3-nitroamino-4
3 system
Synthesis –methylfurazan
of 3‐nitroamino‐4 with NOwith
–methylfurazan 2 BF4 NO
system
2BF[46].
4 system [46].
(3) Fischer
100% HNO et al.system
3
[47] synthesized 3,3′‐diamino‐4,4′‐bifurazan (64) using glyoxal and
(3) 100% HNO system
hydroxylamine by nucleophilic addition,
3 chlorination, substitution, nucleophilic addi‐
tion,Fischer
and et al. [47] reactions.
cyclization synthesized 3,30 -diamino-4,4
Then, compound
0 -bifurazan (64) using glyoxal and hy-
64 was slowly added (64) to 100% HNO 3 at
droxylamine by nucleophilic addition, chlorination, substitution, nucleophilic using
Fischer et al. [47] synthesized 3,3′‐diamino‐4,4′‐bifurazan glyoxal
addition, and
−5 °C to
hydroxylamine 0 °C, and stirred
by nucleophilicfor 45 min.
addition,The suspension was poured onto ice and
and cyclization reactions. Then, compound 64 waschlorination,
slowly added substitution,
to 100% HNO3 nucleophilic
at 5 C addi‐
3,3′‐dinitroamino‐4,4′‐furazan (65) was obtained by filtering and washing with ice water,
0 -dinitroamino-
to 0 C,and
tion, andcyclization
stirred for 45reactions.
min. The suspension was poured
Then, compound 64onto
wasice and 3,3added
slowly to 100% HNO3 at
with a yield of 80%. The synthesis route is shown in Scheme 33. The yield can be in‐
−50 -furazan
4,4 °C to (65)0 °C,wasand obtained by filtering
stirred for 45and washing
min. The with ice water, was
suspension with apoured
yield of 80%.
onto ice and
creased
The to more
synthesis routethan
is 90% by
shown in using an
Scheme organic
33. The solvent
yield can be(such as ethyl
increased to acetate)
more to extract
than 90% by ice water,
3,3′‐dinitroamino‐4,4′‐furazan
filtrate. (65) was obtained by filtering and washing with
using an organic solvent (such as ethyl acetate) to extract filtrate.
with a yield of 80%. The synthesis route is shown in Scheme 33. The yield can be in‐
creased to more than 90% by using an organic solvent (such as ethyl acetate) to extract
filtrate.
0 -dinitramino-4,40 -bifurazane [47].

Scheme 33. Synthesisofof3,3
3,3′‐dinitramino‐4,4′‐bifurazane [47].
(4) HNO33/Ac
(4) HNO /Ac22OOsystem
system
Zhang
Zhangetetal.al.[48]
[48]added
added compound
compound (66)(66)
in batches to a mixture
in batches of acetic
to a mixture of anhydride and
acetic anhydride
100% HNO
Scheme 33.
3 at 0 C.
Synthesis Theofreaction mixture was stirred
3,3′‐dinitramino‐4,4′‐bifurazane for 6 h at
[47].room
and 100% HNO3 at 0 °C. The reaction mixture was stirred for 6 h at room temperaturetemperature and then
poured intopoured
ice water. 0 0 -bis [3-(methyl-azo-nitrogen oxide) furazan-4-yl]
and then N,N
into ice-dinitro-N,N
water. N,N’‐dinitro‐N,N’‐bis [3‐(methyl‐azo‐nitrogen oxide)
methylene
(4) HNO
furazan‐4‐yl]diamine
3/Ac 2O(67) was
system
methylene obtained
diamine bywas
(67) filtering and washing
obtained the precipitate
by filtering and washingwiththe
ethanol
precip‐
in a yield of 66%. The synthesis route is shown in Scheme 34. In this nitration system,
itate with
Zhang ethanol
et al.in[48]
a yield
addedof 66%. The synthesis
compound (66) inroute
batchesis shown in Scheme
to a mixture of 34. In this
acetic anhydride
nitration system, the acid anhydride can effectively reduce the
and 100% HNO3 at 0 °C. The reaction mixture was stirred for 6 h at room temperature oxidizing property of
HNO 3, preventing the generation of by‐products. The reaction has simple operation
and then poured into ice water. N,N’‐dinitro‐N,N’‐bis [3‐(methyl‐azo‐nitrogen oxide)
procedures and a high yield.
furazan‐4‐yl] methylene diamine (67) was obtained by filtering and washing the precip‐
itate with ethanol in a yield of 66%. The synthesis route is shown in Scheme 34. In this
nitration system, the acid anhydride can effectively reduce the oxidizing property of
Scheme 33. Synthesis of 3,3′‐dinitramino‐4,4′‐bifurazane [47].

Zhang et al. [48] added compound (66) in batches to a mixture of acetic anhydride
and 100% HNO3 at 0 °C. The reaction mixture was stirred for 6 h at room temperature
and then poured into ice water. N,N’‐dinitro‐N,N’‐bis [3‐(methyl‐azo‐nitrogen oxide)
Molecules 2022, 27, 1465
furazan‐4‐yl] methylene diamine (67) was obtained by filtering and washing the precip‐
14 of 20
itate with ethanol in a yield of 66%. The synthesis route is shown in Scheme 34. In this
nitration system, the acid anhydride can effectively reduce the oxidizing property of
HNO3, preventing the generation of by‐products. The reaction has simple operation
the acid anhydride can effectively reduce the oxidizing property of HNO3 , preventing the
procedures and a high yield.
generation of by-products. The reaction has simple operation procedures and a high yield.
0 0
Scheme34. Synthesis of N,N -dinitro-N,N
Scheme 34. -bis[3-(methyl-NNO-azoxy)furazan-4-yl]methylenediamine
Synthesis [48]. of
N,N’‐dinitro‐N,N’‐bis[3‐(methyl‐NNO‐azoxy)furazan‐4‐yl]methylenediamine [48].
(5) N2 O5 system
(5) Klapötke
Molecules 2022, 27, x FOR PEER REVIEW et al. [49] cooled dichloromethane (CH2 Cl2 ) to
N2O5 system 20 C and added N2 O5 , 15 of 20
whileKlapötke
keeping the temperature at 20 C. After it was completely dissolved, 3-amino-4-
et al. [49] cooled dichloromethane (CH2Cl2) to −20 °C and added N2O5,
nitrofurazan
while keepingwas slowly added at 20at C.−20
the temperature The °C.
solution wasitslowly
After was warmed up todissolved,
completely 0–5 C
and stirred for 3 h. The solvent was removed under a constant nitrogen stream until most
3‐amino‐4‐nitrofurazan was slowly added at −20 °C. The solution was slowly warmed
of the solvent was removed and 3-nitramino-4-nitrofurazan (68) was obtained in a yield of
up to 0–5 °C and stirred for 3 h. The solvent was removed under a constant nitrogen
66%. The synthesis route is shown in Scheme 35.
stream until most of the solvent was removed and 3‐nitramino‐4‐nitrofurazan (68) was
obtained in a yield of 66%. The synthesis route is shown in Scheme 35.
Scheme 35. Synthesis of 3‐nitramino‐4‐nitrofurazan [49].
3. Nitrification of Azines as Nitrogen‐Rich Heterocyclic Energetic Compounds

Scheme 35.Synthesis
Scheme35. Synthesisof 3-nitramino-4-nitrofurazan [49]. [49].
of 3‐nitramino‐4‐nitrofurazan
3.1. Pyridazines
3. Nitrification of Azines as Nitrogen-Rich Heterocyclic Energetic Compounds
Nitrification
3. Pyridazinesof H
Nitrification
3.1. of on Pyridazine
Azines Ring C
as Nitrogen‐Rich Heterocyclic Energetic Compounds
Nitrification of H on et
Gospodinov
3.1. Pyridazines Pyridazine
al. [50] Ring C
prepared the compound 3,5‐dimethoxypyridazine‐1‐oxide
(69) Gospodinov et al.
on[50]
using dichloropyridazine
Nitrification of H preparedasthe
Pyridazine a compound
Ringraw 3,5-dimethoxypyridazine-1-oxide
C material by substitution reaction and (69) oxidation
using dichloropyridazine
reaction, and then used as atwo
raw material
nitrationby systems
substitution
to reaction
obtain and oxidation 70.
compound reaction,
The synthesis
and Gospodinov
then et al. [50] prepared the compound 3,5‐dimethoxypyridazine‐1‐oxide
route is used
showntwoinnitration
Schemesystems
36. to obtain compound 70. The synthesis route is shown
(69) using
in Scheme 36. dichloropyridazine as a raw material by substitution reaction and oxidation
reaction, and then used two nitration systems to obtain compound 70. The synthesis
route is shown in Scheme 36.
Scheme 36.Synthesis
Scheme36. Synthesisof 3,6-diamino-4,6-dinitropyridazine-1-oxide [50].
of 3,6‐diamino‐4,6‐dinitropyridazine‐1‐oxide [50].
(1) 20% H2 SO4 /100% HNO3 system
(1) 20% H2SO4/100% HNO3 system
Compound
Scheme 69 wasofdissolved
36. Synthesis in 20% fuming H2 SO4 at 5 C, after[50].
3,6‐diamino‐4,6‐dinitropyridazine‐1‐oxide which, NaNO3 was
addedCompound 69 reaction
in batches, the was dissolved
mixture in
was20% fuming
stirred for 1 h, SO4was
H2and at 5then
°C, after
slowlywhich,
warmedNaNO3 was
up to
added room
in temperature.
batches, the After
(1) 20% H2SO4/100% HNO3 system that,
reaction the
mixturereaction
was mixture
stirred was
for 1stirred
h, andovernight
was thenat 60 C warmed
slowly
up to room temperature. After that, the reaction mixture was stirred overnight at 60 °C
Compound 69 was dissolved in 20% fuming H2SO4 at 5 °C, after which, NaNO3 was
and then poured onto crushed ice. The resulting suspension was stirred until the ice
added in batches, the reaction mixture was stirred for 1 h, and was then slowly warmed
dissolved and the resulting precipitate was filtered. The crude product was dissolved in
up to room temperature. After that, the reaction mixture was stirred overnight at 60 °C
conc. H2SO4, stirred for 3 h at 60 °C, and then poured on ice and the precipitate was fil‐
tered. 3,5‐dimethoxy‐4,6‐dinitropyridazine‐1‐oxide (70) was obtained after washing with
dissolved and the resulting precipitate was filtered. The crude product was dissolved in
Molecules 2022, 27, 1465 15 of 20
dissolved and the resulting precipitate was filtered. The crude product was dissolved
in conc. H2 SO4 , stirred for 3 h at 60 C, and then poured on ice and the precipitate was
filtered. 3,5-dimethoxy-4,6-dinitropyridazine-1-oxide (70) was obtained after washing with
ice water several times in a yield of 13%.
(2) 20% H2 SO4 /100% NaNO3 system
Compound 69 was dissolved in 20–25% fuming H2 SO4 at 10 C, and 100% HNO3
was added dropwise below 8 C. The reaction mixture was first stirred at 0 C for 1.5 h,
then at room temperature for 2 h, and finally stirred at 45–50 C for 20 h. After cooling,
the reaction was poured onto crushed ice. The resulting suspension was stirred for 2 h
Molecules 2022, 27, x FOR PEER REVIEW 16 of
and the obtained yellowish precipitate was filtered off and washed with water. The crude
product was dissolved in conc. H2 SO4 and stirred at 60 C for 2 h. The mixture was poured
onto crushed ice, filtered, and washed with ice water to obtain compound 70 in a yield of
28%. Finally, 3,6-diamino-4,6-dinitropyridazine-1-oxide (71) was synthesized by reacting
3.2. Pyrazines
compound 70 with concentrated ammonia in acetonitrile solution.
Nitrification of H on Pyrazine Ring C
3.2. Pyrazines
The density of 2,6‐diamino‐3,5‐dinitropyrazine‐1‐oxide (LLM‐105, 73) is 1.92 g∙cm
Nitrification of H on Pyrazine Ring C
with the detonation velocity of 8516 m∙s and the detonation pressure of 35.9
−1 GPa. It is
The density of 2,6-diamino-3,5-dinitropyrazine-1-oxide (LLM-105, 73) is 1.92 g·cm 3
new explosive with excellent energy and safety performance. In the process of its pre
with the detonation velocity of 8516 m·s 1 and the detonation pressure of 35.9 GPa. It
aration, there is with
is a new explosive a typical nitration
excellent energy andreaction of H on pyrazine
safety performance. C, andof the
In the process its preparatio
preparation,
method of there is a typical
LLM‐105 has nitration reaction of HInon2014,
been improving. pyrazineZhouC, and the [51]
et al. preparation
used two nitratio
method
systems of LLM-105 has been
to nitrate theimproving. In 2014,2,6‐diacetamidopyrazine‐1‐oxide
intermediate Zhou et al. [51] used two nitration systems
(72) to obta
to nitrate the intermediate 2,6-diacetamidopyrazine-1-oxide
LLM‐105. The synthesis route is shown in Scheme 37. (72) to obtain LLM-105. The
synthesis route is shown in Scheme 37.
Scheme Synthesis
Scheme37.37. of 2,6-diamino-3,5-dinitropyrazine-1-oxide
Synthesis [51].
of 2,6‐diamino‐3,5‐dinitropyrazine‐1‐oxide [51].
(1) 20% H2 SO4 /100% HNO3 system
(1) 20% H2SO4/100% HNO3 system
Compound 72 was added into 20% fuming H2 SO4 when the temperature was lower
than 25Compound 72 wasofadded
C, the temperature intowas
the mixture 20%controlled
fumingtoHbe 2SO 4 when
lower than the
10 C temperature
at the end was low
of feeding,
than 25 °C,andthethen fuming HNOof
temperature 3 was
theslowly added
mixture wasinto the mixture.
controlled to Afterwards,
be lower the
than 10 °C at t
system was controlled to react for 1 h within 10–15 C and then heated to room
end of feeding, and then fuming HNO3 was slowly added into the mixture. Afterward temperature
for 2 h. Finally, the mixture was poured onto crushed ice, filtered, washed with water, and
the system was controlled to react for 1 h within 10–15 °C and then heated to room tem
dried to obtain the bright yellow LLM-105 solid with the yield of 72%.
perature for 2 h. Finally, the mixture was poured onto crushed ice, filtered, washed wi
(2) 100% HNO3 /TMPSHSO4 system
water, and dried to obtain the bright yellow LLM‐105 solid with the yield of 72%.
N,N,N-trimethyl-N-propanesulfonate-ammonium bisulfate (TMPSHSO4 ), as an ionic
liquid,
(2) 100%was dissolved in fuming HNO
HNO3/TMPSHSO 3 , cooled to about 0 C, and then compound 72 was
4 system
slowly added. The reaction solution was stirred for 0.5 h; then heated to 25 C, reacting for
N,N,N‐trimethyl‐N‐propanesulfonate‐ammonium
1 h; and bisulfate (TMPSHSO
heated to 75 C, reacting for 4 h. After the reaction was completed, the mixture 4), as an io
was cooled was
ic liquid, to room temperature,
dissolved diluted HNO
in fuming with distilled water,
3, cooled filtered0and
to about °C,washed withcompound
and then
water three times, and dried to obtain yellow LLM-105, with a yield of 68.4%. Compared
was slowly added. The reaction solution was stirred for 0.5 h; then heated to 25 °C, r
with nitration with mixed acid, HNO3 /acid ionic liquid has the advantages of simpler
acting for 1 h; and heated to 75 °C, reacting for 4 h. After the reaction was completed, t
post-treatment and less waste acid discharge.
mixture was cooled to room temperature, diluted with distilled water, filtered an
washed with water three times, and dried to obtain yellow LLM‐105, with a yield
68.4%. Compared with nitration with mixed acid, HNO3/acid ionic liquid has the a
vantages of simpler post‐treatment and less waste acid discharge.
(3) H2SO4/95% HNO3 system

Liu et al. [52] synthesized 2,6‐dipyramidopyrazine (74) usin
2,4,6‐trinitrochlorobenzene and 2,6‐diaminopyrazine by condensation reaction. Nex
mixture was cooled to room temperature, diluted with distilled water,
washed with water three times, and dried to obtain yellow LLM‐105, w
68.4%. Compared with nitration with mixed acid, HNO3/acid ionic liqui
vantages of simpler post‐treatment and less waste acid discharge.
Molecules 2022, 27, 1465

(3) H2SO4/95% HNO3 system 16 of 20
Liu et al. [52] synthesized 2,6‐dipyramidopyrazine
2,4,6‐trinitrochlorobenzene and 2,6‐diaminopyrazine by condensation re
(3) H2 SO4 /95% HNO3 system
95% fuming HNO3 and concentrated H2SO4 were stirred for 0.5 h at 0 °
Liu et al. [52] synthesized 2,6-dipyramidopyrazine (74) using 2,4,6-trinitrochlorobenzene
compound 74 was by
and 2,6-diaminopyrazine slowly added,
condensation andNext,
reaction. then 95%the temperature
fuming was gradually
HNO3 and concen-
trated
°C H23
for SOh.
4 were stirred for 0.5 h at
Subsequently, the0 C. After that,solution
reaction compound was74 wascooled,
slowly added, and into ice w
poured
then the temperature was gradually raised to 50 C for 3 h. Subsequently, the reaction solution
and washed with acetone, and dried in a vacuum to obtain 2,6‐dipyramid
was cooled, poured into ice water, filtered and washed with acetone, and dried in a vacuum
pyrazine (BPNP, 75). The yield
to obtain 2,6-dipyramido-3,5-dinitro- was
pyrazine 66%.
(BPNP, 75). The synthesis
The yield was 66%. route is shown in Sc
The synthesis
Molecules 2022, 27, x FOR PEER REVIEW 17
3.3.
Molecules 2022, 27, x FOR PEER REVIEW Nitrification of ‐NH2 Connected with Triazine Ring C 17 of 20
Huang et al. [53] synthesized 6‐amino‐2,4‐diazio[1,3,5]triazine (76) using cya

acid chloride with aqueous NH3 at 0 °C and then sodium azide in acetone/H2O(1:1
3.3. Nitrification
ter that, compound 2 Connected
of ‐NH(76) was addedwith Triazine
to HNO Ring C
3 (100%) in batches below 5 °C, after w
Scheme
Scheme 38.
the reaction
Huang Synthesis
38. et of
Synthesis
mixture BPNP
al. [53] was[52].
of BPNP
stirred
synthesized [52].
for 30 min at 0 °C, slowly warmed
6‐amino‐2,4‐diazio[1,3,5]triazine up tocyanuric
(76) using room tem
ature,
acid
3.3. and stirred
chloride
Nitrification of -NHfor
with another
aqueous
2 Connected
NHwith
3 3 Triazine
h. Afterwards,
at 0 °C and then
Ring C the reaction mixture was pouredAf‐
sodium azide in acetone/H 2O(1:1). ont
ter that,
filtered, compound
washed (76) was
with addedcoldto HNO 3 (100%)and
water, in batches below
dried 5
in
Huang et al. [53] synthesized 6-amino-2,4-diazio[1,3,5]triazine (76) using cyanuric acid °C, after
air which
to o
the reaction
chloride with mixture
aqueous NHwas atstirred
0
2‐nitroamino‐4,6‐diazo[1,3,5]triazine
3 C andfor 30
then min
sodiumat 0 °C,
azide inslowly warmed
acetone/H
(77) in a yield of 54%. up
O(1:1). to
After room
that, temper‐
2 The synthesis route is sh
compound
ature,
in Schemeand(76) was added
stirred
39. to HNO33 h.
for another (100%) in batchesthe
Afterwards, below 5 C, after
reaction whichwas
mixture the reaction
poured onto ice,
mixture
filtered,was stirred
washed for 30 min
withat 0 cold
C, slowlywater,
warmed up to roomdried
and temperature,
in andairstirred
to obtain
for another 3 h. Afterwards, the reaction mixture was poured onto ice,
2‐nitroamino‐4,6‐diazo[1,3,5]triazine (77) in a yield of 54%. The synthesisfiltered, washed
route is shown
with cold water, and dried in air to obtain 2-nitroamino-4,6-diazo[1,3,5]triazine (77) in a
in Scheme 39.
yield of 54%. The synthesis route is shown in Scheme 39.
Scheme 39. Synthesis of 2‐Nitroamino‐4,6‐diazido[1,3,5]triazine [53].
Scheme
Scheme 39.Synthesis
39.
3.4. Nitrification
Synthesisof 2-Nitroamino-4,6-diazido[1,3,5]triazine
of ‐NH
of 2 on Tetrazine Ring C [53].
2‐Nitroamino‐4,6‐diazido[1,3,5]triazine [53].
3.4. Nitrification
Zhang etof al.
-NH[54]
2 on Tetrazine
added Ring C
3,6‐diamino‐1,2,4,5‐tetrazine to fuming HNO3 at 0 °C,
3.4. Nitrification
Zhang etstirred of ‐NH
al. [54] added2 on Tetrazine Ring C
gradually for 1 3,6-diamino-1,2,4,5-tetrazine to fuming HNO3 at 0 C, then
h, filtered, and dried. 3,6‐dinitroamino‐1,2,4,5‐tetrazine (D
gradually
Zhang stirred
et for[54]
al. 1 h, filtered,
added and dried. 3,6-dinitroamino-1,2,4,5-tetrazine
3,6‐diamino‐1,2,4,5‐tetrazine to fuming (DNAT,3 78)
HNOyield.
at 0 °C, then
78) was obtained by recrystallization from ethyl acetate with 85.0% The syn
was obtainedstirred
gradually by recrystallization from ethyl
for 1 h, filtered, and acetate
dried.with 85.0% yield. The synthesis route (DNAT,
3,6‐dinitroamino‐1,2,4,5‐tetrazine
route
is shownisinshown
Scheme in40.Scheme 40.
78) was obtained by recrystallization from ethyl acetate with 85.0% yield. The synthesis
Scheme
Scheme Synthesis
40.40. of 3,6-dinitroamine-1,2,4,5-tetrazine
Synthesis [54].
of 3,6‐dinitroamine‐1,2,4,5‐tetrazine [54].
4. Conclusions
Scheme 40. Synthesis of 3,6‐dinitroamine‐1,2,4,5‐tetrazine [54].
4. Conclusions
The characteristics of the used nitration agents are listed in Table 1.
4. Conclusions
Table 1. Characteristics of different nitrification systems.
Nitrification System Characteristic
HNO3 Cheap. To nitrate different azole rings, different concentrations of HNO3 are requi
HNO3 Cheap. To nitrate different azole rings, different concentrations of HNO3 are required.
Thenitration
The nitrationability
ability
is is stronger
stronger than
than thatthat of HNO
of HNO 3, and it is often used for the nitra
3, and it is often used for the nitration
Molecules 2022, 27, 1465 17 of 20

Cheap. To nitrate different azole rings, different concentrations of HNO3
HNO3
are required.
The nitration ability is stronger than that of HNO3 , and it is often used
for the nitration of a variety of azole compounds. According to the
structural characteristics of different azole rings and the difficulty of the
aromatic electrophilic substitution reaction, a suitable ratio of
HNO3 /H2 SO4 should be selected for nitration. The reaction conditions
HNO3 /H2 SO4 are mostly mild, the required temperature range is generally from 20 C
to 100 C, the reaction time is about 1 h to 2.5 h, and the yield can reach
about 80% or higher. For some azole substrates with relatively inert
reaction activity (such as the existence of strong electron-withdrawing
group), the reaction rate is generally slow and the reaction time needs to
be extended to 10–48 h.
Compared with the nitrating reagent HNO3 /H2 SO4 , the HNO3 /Ac2 O
HNO3 /Ac2 O mixture has a weaker nitrification ability, but the acid anhydride can
effectively reduce the oxidation of HNO3 .
An environmentally friendly nitrating reagent without waste acid
treatment. The reaction condition is relatively mild, and the temperature
is easy to control. It is non-oxidizing and has high reaction selectivity. It
NO2 BF4
can be used for the aromatic electrophilic nitration reaction of various
azole rings, acetonitrile is often used as the solvent, the reaction time is
generally 10 h, and the yield is 30–50%.
N2 O5 is a green nitrification reagent that can be used for the nitration of
sensitive compounds. Compared with nitration reagents such as HNO3 ,
HNO3 /H2 SO4 , HNO3 /acid anhydride, it has the following advantages:
no need for waste acid treatment, the reaction has less heat release and
N2 O5
the temperature is easy to control, the post-treatment is simple as only
the solvent needs to be evaporated, the reaction is usually carried out
with CH2 Cl2 as solvent, the temperature is generally from 20 C to 100
C, and the yield is about 90%.
In this system, P2 O5 is not only a dehydrating agent, but also a
HNO3 /P2 O5 nitrification accelerator. The nitration system is suitable for the nitration
of aromatics as well as amines.
Under catalysis, some nitrates can also act as nitrating reagents, which
are mainly used in the synthesis of some nitropyrazole compounds.
Nitrate
Their nitrating capacities are as follows: Bi(NO3 )3 > AgNO3 > KNO3 >
NaNO3 > NH4 NO3 > Pb(NO3 )2 > Ba(NO3 )2 .
The nitration methods of nitrogen-rich heterocyclic EMs of azoles (imidazole, pyrazole,

triazole, tetrazole, oxadiazole) and azines (pyrazine, pyridazine, triazine, tetrazine) were
reviewed. Most of the above nitro-containing nitrogen-rich heterocyclic EMs have higher
density, outstanding enthalpy of formation, and excellent oxygen balance. Generally
speaking, nitrogen-rich compounds with high density and enthalpy of formation always
have high detonation performance. Although there are many nitration methods of nitrogen-
rich heterocyclic EMs reported in the literature, there are still some problems that need to
be explored and studied. The authors believe that the following aspects of research should
be noted in the future:
1. Nitramino-containing nitrogen-rich EMs have higher sensitivity, and these materials
can be used as primary explosives. From the viewpoint of chemical reactivity, the nitro
group attached to the heterocyclic carbon adjacent to the nitrogen on the heterocyclic
ring is unstable to hydrolysis. The existence of adjacent C-amino groups will improve
the stability of the ring, and the lone pair of electrons on the amino nitrogen provides
electrons to the ring system, thus, the sensitivity of the nitro group to hydrolysis can
Molecules 2022, 27, 1465 18 of 20
be significantly reduced. In addition, the presence of amino and nitro groups will
boost the formation enthalpy, oxygen balance, density, and stability of the compound,
thereby enhancing the detonation and safety of the compound [6,20,55]. Therefore,
when designing the molecular structure of EMs, it should be designed as far as
possible with compounds where nitro and amino groups cross, such as 3,6-diamino-
4,6-dinitropyridazine-1-oxide (Scheme 36) and 2,6-diamino-3,5-dinitropyrazine-1-
oxide (LLM-105) (Scheme 37);
2. Applying organic synthesis technologies, such as ultrasound and microwave, to the
nitration process of nitrogen-rich heterocyclic energetic compounds to shorten the
time and improve the overall yield is imperative;
3. In view of the traditional methods for synthesizing nitro-containing heterocyclic en-
ergetic compounds, including a series of problems brought about by the application
of oleum sulfuric acid and fuming nitric acid, it is necessary to continue research so
as to discover new nitrification methods to adapt to new needs, especially paying
more attention to the development of some low-toxic, cheap, efficient, and environ-
mentally friendly nitrification strategies to adapt to the implementation of sustainable
development strategies and the practical application of green chemistry.
Author Contributions: Conceptualization, X.W. and Y.L.; investigation, W.Z. and F.S.; writing—
original draft preparation, Y.L. and W.Z.; writing—review, X.W. and Y.L.; editing, F.S.; Y.L. and W.Z.
contributed equally to this work. All authors have read and agreed to the published version of
the manuscript.
Funding: This research received no external funding.
Institutional Review Board Statement: Not applicable.
Informed Consent Statement: Not applicable.
Data Availability Statement: Not applicable.
Conflicts of Interest: The authors declare no conflict of interest.
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Abrir Nitrification Progress of Nitrogen-Rich Heterocycl

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Abrir Nitrification Progress of Nitrogen-Rich Heterocycl

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molecules

Abstract: As a momentous energetic group, a nitro group widely exists in high-energy-density

Molecules 2022, 27, 1465. https://doi.org/10.3390/molecules27051465 https://www.mdpi.com/journal/molecules

Molecules 2022, 27, 1465 2 of 20

Scheme 2. Synthesis of 4,4′,5,5′‐tetranitro‐2,2′‐biimidazole [15].

small amount of water. The light yellow solid, 2-nitroammonium-5,6-dinitrobenz imidazole

Molecules 2022, 27, 1465 3 of 20

2.2. Nitrification of Pyrazoles

(1) Bismuth nitrate/montmorillonite

Molecules 2022, 27, 1465 2.2. Nitrification

Scheme 6. Synthesis of 1‐methyl‐5‐nitropyrazole‐ 2‐oxide (K‐10) [19].

(2) HNO3/H2SO4 system

Scheme 7. Synthesis of 4-chloro-3,5-dinitropyrazole [20].

Scheme 8. Synthesis of N‐(6‐(3,5‐dimethyl‐4‐nitro‐1H‐pyrazol‐1‐yl)

Scheme 11. Synthesis of 4‐(N‐methylnitramino)‐3,5‐dinitropyrazole [24].

2.2.3. Nitrification of Nitrification

Scheme 12. Synthesis 12.0 -dinitro-1H,1H’-3,3

(2) NH4 NO3 /TFAA

Scheme 14. Synthesis of N,N’‐ (3,6‐dinitropyrazole [4,3‐c] pyrazole‐1,4‐diyl) dinitramine [27].

connected with N in a pyrazole

Scheme 14. Synthesis of N,N’‐ (3,6‐dinitropyrazole [4,3‐c] pyrazole‐1,4‐diyl) dinitramine [27].

Molecules 2022, 27, x FOR PEER REVIEW 8 of 20

(2) HNO3 /Ac2 O system

Scheme 17. Synthesis of 3,3′‐dinitrimino‐5,5′‐bis(1H‐1,2,4‐triazole) [33].

Scheme 20. Synthesis of 5,5′‐diamino‐4,4′‐dinitramino‐3,3′‐bi‐1,2,4‐triazole [35].

Scheme 20. Synthesis of 5,50 -diamino-4,40 -dinitramino-3,30 -bi-1,2,4-triazole [35].

Molecules 2022, 27, x FOR PEER REVIEW 10 of 20

Stierstorfer et al. [38] dissolved 1-(2-azidoethyl)-5-aminotetrazole (40) in MeCN in

and the water was evaporated. Potassium 1‐(2‐azidoethyl)‐5‐nitroaminotetrazole (41)

(3) 100% HNO system

Scheme 26. Synthesis of 5‐amino‐1‐nitriminotetrazole [41].

Scheme 27. Synthesis of 1,1′‐dinitramino‐5,5′‐azobitetrazole [42].

0 -dinitramino-3,30 -azo-1,2,4-oxadiazole [43].

Scheme 29. Synthesis of 3‐amino‐5‐nitramino‐1,2,4‐oxadiazole monohydrate [44].

Scheme 30. Synthesis

2.5.3. Nitration of ‐NH2 Connected with 1,2,5‐Oxadiazole(Furazan) Ring C

(1) N2O4/100% HNO3 system

(1) N2O4/100% HNO3 system

0 -dinitramino-4,40 -bifurazane [47].

(4) HNO3/Ac2O system

Scheme 35. Synthesis of 3‐nitramino‐4‐nitrofurazan [49].

3. Nitrification of Azines as Nitrogen‐Rich Heterocyclic Energetic Compounds

(3) H2SO4/95% HNO3 system

Molecules 2022, 27, 1465

Molecules 2022, 27, x FOR PEER REVIEW 17

Huang et al. [53] synthesized 6‐amino‐2,4‐diazio[1,3,5]triazine (76) using cya

Scheme 39. Synthesis of 2‐Nitroamino‐4,6‐diazido[1,3,5]triazine [53].

Table 1. Characteristics of different nitrification systems.

Nitrification System Characteristic

The nitration methods of nitrogen-rich heterocyclic EMs of azoles (imidazole, pyrazole,

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