Nitrification Progress of Nitrogen-Rich Heterocyclic Energetic Compounds: A Review

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.


Introduction
Nitrogen-rich compounds have attracted widespread attention in energetic materials (EMs) because of their advantages of outstanding density, excellent positive enthalpy of formation, remarkable detonation performance, and high thermal stability [1][2][3]. They can be used in explosives, propellants, gas generators, and smokeless pyrotechnic fuels [4,5]. In order to meet the increasing performance requirements, new nitrogen-rich EMs are being developed with upgradable density, better detonation performance, lower impact and friction sensitivity, and higher thermal stability.
The main skeletons of nitrogen-rich heterocyclic energetic compounds are azole rings (imidazole, pyrazole, triazole, tetrazole, oxadiazole) and azine rings (pyrazine, pyridazine, triazine, tetrazine) [11,12]. Different nitration systems can be used to nitrate specific compounds on the basis of the structural characteristics of compounds [13]. According (2) 80% HNO3/H2SO4 system• Li et al. [15] synthesized BI using ammonium acetate (CH3COONH4) and glyoxal as raw materials. Then, BI was added to 95-98% concentrated H2SO4 at 20-25 °C. After that, the mixed solution of 80% HNO3 and 95-98% H2SO4 was added dropwise as the mixture was heated to 45 °C. Four hours later, the reaction solution was poured onto crushed ice, filtered, washed with cold water, and dried to obtain TNBI. The synthesis route is shown in Scheme 2. The yield was 51.7%. Compared with the traditional operation process [14], this strategy saves the reaction time and lowers the reaction temperature via a gentle and stable reaction process, thus, the danger of the reaction is reduced. Scheme 2. Synthesis of 4,4′,5,5′-tetranitro-2,2′-biimidazole [15].

Nitration of -NH2 on Imidazole Ring C/N
The H atom of NH2 can be nitrified to obtain different nitration products using the HNO3/H2SO4 system.

/H 2 SO 4 system
Li et al. [15] synthesized BI using ammonium acetate (CH 3 COONH 4 ) and glyoxal as raw materials. Then, BI was added to 95-98% concentrated H 2 SO 4 at 20-25 • C. After that, the mixed solution of 80% HNO 3 and 95-98% H 2 SO 4 was added dropwise as the mixture was heated to 45 • C. Four hours later, the reaction solution was poured onto crushed ice, filtered, washed with cold water, and dried to obtain TNBI. The synthesis route is shown in Scheme 2. The yield was 51.7%. Compared with the traditional operation process [14], this strategy saves the reaction time and lowers the reaction temperature via a gentle and stable reaction process, thus, the danger of the reaction is reduced.
Molecules 2022, 27, x FOR PEER REVIEW 2 of 20 pyridazine, triazine, tetrazine) [11,12]. Different nitration systems can be used to nitrate specific compounds on the basis of the structural characteristics of compounds [13]. According to the diversity of the nitration positions on these frameworks, this paper classifies the nitration of H on heterocyclic C, the nitration of -NH2 on heterocyclic C, the nitration of H on heterocyclic N, and the nitration of -NH2 on heterocyclic N.
(2) 80% HNO3/H2SO4 system• Li et al. [15] synthesized BI using ammonium acetate (CH3COONH4) and glyoxal as raw materials. Then, BI was added to 95-98% concentrated H2SO4 at 20-25 °C. After that, the mixed solution of 80% HNO3 and 95-98% H2SO4 was added dropwise as the mixture was heated to 45 °C. Four hours later, the reaction solution was poured onto crushed ice, filtered, washed with cold water, and dried to obtain TNBI. The synthesis route is shown in Scheme 2. The yield was 51.7%. Compared with the traditional operation process [14], this strategy saves the reaction time and lowers the reaction temperature via a gentle and stable reaction process, thus, the danger of the reaction is reduced. Scheme 2. Synthesis of 4,4′,5,5′-tetranitro-2,2′-biimidazole [15].

Nitration of -NH2 on Imidazole Ring C/N
The H atom of NH2 can be nitrified to obtain different nitration products using the HNO3/H2SO4 system. Thomas

Nitration of -NH 2 on Imidazole Ring C/N
The H atom of NH 2 can be nitrified to obtain different nitration products using the HNO 3 /H 2 SO 4 system.
Thomas et al. [16] added 2-aminobenzimidazole (1) to the solution of 100% HNO 3 and concentrated H 2 SO 4 (96-98%) while stirring at 0 • C. After stirring for 48 h at 25 • C, the mixture was poured onto crushed ice, then filtered and washed with 20% HNO 3 and a 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, x FOR PEER REVIEW 3 of 20 a 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.
Another example is nitration of -NH2 on imidazole ring N. Yin et al. [17] synthesized 4,4′,5,5′-tetranitro-1H,1′H-(2,2′-benzimidazole)-1,1′-diamine (4) from glyoxal and ammonium acetate by using condensation, nitration, and N-amination reactions. Compound 4 was then slowly added to the HNO3/H2SO4 solution at −10 °C and stirred for 90 min. The solution was subsequently poured onto crushed ice, stirred for about 10-15 min, filtered, and washed with ice-cooled water, ethanol, and ether to obtain N,N'-dinitroamino-4,4′,5,5′-tetranitro-bisimidazole (5). The synthesis route is shown in Scheme 4. In order to prevent the N-N bond from being broken, the nitration reaction should be performed in a mixed acid at a temperature of −15 to −10 °C because the N-amino group is highly reactive. It has been found that the nitrification ability of HNO3/H2SO4 is stronger than that of HNO3, so HNO3/H2SO4 with an appropriate ratio is always selected for nitrating NH2 to NHNO2. The reaction condition is mostly mild and the operation is simple. (1) HNO3/Ac2O system Chand et al. [18] synthesized compound 7 using benzimidazole as a raw material through iodination, nitration, substitution, and ring formation reactions (Scheme 5). Then, 100% HNO3 was added dropwise to acetic anhydride (Ac2O) at −5 °C, and the resulting mixture was stirred for 0.5 h. Compound 7 was then added to the reaction solution in portions and stirred for 2 h. Afterwards, the reaction mixture was poured onto crushed ice. Compound 8 was obtained by filtration with a yield of 67%. Compared with the nitrifying agent HNO3/H2SO4, 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 3. Synthesis of 2-nitrimino-5,6-dinitrobenzimidazole [16].
Another example is nitration of -NH 2 on imidazole ring N. Yin et al. [17] synthesized 4,4 ,5,5 -tetranitro-1H,1 H-(2,2 -benzimidazole)-1,1 -diamine (4) from glyoxal and ammonium acetate by using condensation, nitration, and N-amination reactions. Compound 4 was then slowly added to the HNO 3 /H 2 SO 4 solution at −10 • C and stirred for 90 min. The solution was subsequently poured onto crushed ice, stirred for about 10-15 min, filtered, and washed with ice-cooled water, ethanol, and ether to obtain N,N -dinitroamino-4,4 ,5,5tetranitro-bisimidazole (5). The synthesis route is shown in Scheme 4. In order to prevent the N-N bond from being broken, the nitration reaction should be performed in a mixed acid at a temperature of −15 to −10 • C because the N-amino group is highly reactive. It has been found that the nitrification ability of HNO 3 /H 2 SO 4 is stronger than that of HNO 3 , so HNO 3 /H 2 SO 4 with an appropriate ratio is always selected for nitrating NH 2 to NHNO 2 . The reaction condition is mostly mild and the operation is simple. Another example is nitration of -NH2 on imidazole ring N. Yin et al. [17] synthesized 4,4′,5,5′-tetranitro-1H,1′H-(2,2′-benzimidazole)-1,1′-diamine (4) from glyoxal and ammonium acetate by using condensation, nitration, and N-amination reactions. Compound 4 was then slowly added to the HNO3/H2SO4 solution at −10 °C and stirred for 90 min. The solution was subsequently poured onto crushed ice, stirred for about 10-15 min, filtered, and washed with ice-cooled water, ethanol, and ether to obtain N,N'-dinitroamino-4,4′,5,5′-tetranitro-bisimidazole (5). The synthesis route is shown in Scheme 4. In order to prevent the N-N bond from being broken, the nitration reaction should be performed in a mixed acid at a temperature of −15 to −10 °C because the N-amino group is highly reactive. It has been found that the nitrification ability of HNO3/H2SO4 is stronger than that of HNO3, so HNO3/H2SO4 with an appropriate ratio is always selected for nitrating NH2 to NHNO2. The reaction condition is mostly mild and the operation is simple. (1) HNO3/Ac2O system Chand et al. [18] synthesized compound 7 using benzimidazole as a raw material through iodination, nitration, substitution, and ring formation reactions (Scheme 5). Then, 100% HNO3 was added dropwise to acetic anhydride (Ac2O) at −5 °C, and the resulting mixture was stirred for 0.5 h. Compound 7 was then added to the reaction solution in portions and stirred for 2 h. Afterwards, the reaction mixture was poured onto crushed ice. Compound 8 was obtained by filtration with a yield of 67%. Compared with the nitrifying agent HNO3/H2SO4, 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. Chand et al. [18] synthesized compound 7 using benzimidazole as a raw material through iodination, nitration, substitution, and ring formation reactions (Scheme 5). Then, 100% HNO 3 was added dropwise to acetic anhydride (Ac 2 O) at −5 • C, and the resulting mixture was stirred for 0.5 h. Compound 7 was then added to the reaction solution in portions and stirred for 2 h. Afterwards, the reaction mixture was poured onto crushed ice. Compound 8 was obtained by filtration with a yield of 67%. Compared with the nitrifying agent HNO 3 /H 2 SO 4 , the nitrifying ability of HNO 3 /Ac 2 O mixed solution is weaker, but Ac 2 O can effectively decrease the oxidizing property of HNO 3 and avoid the formation of by-products of compound 8.  3 ) in tetrahydrofuran (THF) and stirred for 2.5 h. The solvent was then evaporated under reduced pressure using a vacuum pump for 5 min. The mixture was repeatedly washed with dichloromethane (CH 2 Cl 2 ) and concentrated to give the crude K-10. The pure product was isolated by column chromatography with a yield of 98%. The synthesis route is shown in Scheme 6. The ranking of nitration capacities of some nitrates is as follows: Bi(NO 3 ) 3 > AgNO 3 > KNO 3 > NaNO 3 > NH 4 NO 3 > Pb(NO 3 ) 2 > Ba(NO 3 ) 2 . In the reaction, Bi(NO 3 ) 3 , which is impregnated on K-10, has a fast nitration rate and high yield and is easy to separate from the product by filtration. The methyl group in the pyrazole ring contributes to the nitration process, and the nitration rate will increase with the number of methyl groups. Scheme 5. Synthesis of 7-nitro-7H-imidazo[4′, 5,5,6]benzo [1][2][3][4] [19] added 1-methylpyrazole-2-oxide and montmorillonite (K-10) t suspension of bismuth nitrate (Bi(NO3)3) in tetrahydrofuran (THF) and stirred for 2.5 The solvent was then evaporated under reduced pressure using a vacuum pump fo min. The mixture was repeatedly washed with dichloromethane (CH2Cl2) and conc trated to give the crude K-10. The pure product was isolated by column chromatograp with a yield of 98%. The synthesis route is shown in Scheme 6. The ranking of nitrati capacities of some nitrates is as follows: Bi(NO3)3＞AgNO3＞KNO3＞NaNO3＞NH4N ＞Pb(NO3)2＞Ba(NO3)2. In the reaction, Bi(NO3)3, which is impregnated on K-10, ha fast nitration rate and high yield and is easy to separate from the product by filtrati The methyl group in the pyrazole ring contributes to the nitration process, and the nit tion rate will increase with the number of methyl groups. Scheme 6. Synthesis of 1-methyl-5-nitropyrazole-2-oxide (K-10) [19].
(2) HNO3/H2SO4 system The HNO3/H2SO4 system usually has a strong nitration effect. Fischer et al. [ synthesized 4-chloropyrazole (9) using pyrazole as a raw material via chlorination re tion. Compound 9 was then dissolved in the concentrated H2SO4, and 100% HNO3 w slowly added below 40 °C. Then, the mixture was heated to 100 °C and stirred for 5 under reflux. After cooling to room temperature, the final solution was poured on crushed ice water and extracted with acetoacetic acid. The organic layers were wash with water, dried over magnesium sulfate, and dried under nitrogen to g 4-chloro-3,5-dinitro-1H-pyrazole (10) in a yield of 86.7%. The synthesis route is shown Scheme 7. The reaction is simple, no further purification is required, and the react yield is high.  (2) HNO 3 /H 2 SO 4 system The HNO 3 /H 2 SO 4 system usually has a strong nitration effect. Fischer et al. [20] synthesized 4-chloropyrazole (9) using pyrazole as a raw material via chlorination reaction. Compound 9 was then dissolved in the concentrated H 2 SO 4 , and 100% HNO 3 was slowly added below 40 • C. Then, the mixture was heated to 100 • C and stirred for 5 h under reflux. After cooling to room temperature, the final solution was poured onto crushed ice water and extracted with acetoacetic acid. The organic layers were washed with water, dried over magnesium sulfate, and dried under nitrogen to give 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.  [19] added 1-methylpyrazole-2-oxide and montmorillonite (K-10) t suspension of bismuth nitrate (Bi(NO3)3) in tetrahydrofuran (THF) and stirred for 2.5 The solvent was then evaporated under reduced pressure using a vacuum pump fo min. The mixture was repeatedly washed with dichloromethane (CH2Cl2) and conc trated to give the crude K-10. The pure product was isolated by column chromatograp with a yield of 98%. The synthesis route is shown in Scheme 6. The ranking of nitrati capacities of some nitrates is as follows: Bi(NO3)3＞AgNO3＞KNO3＞NaNO3＞NH4N ＞Pb(NO3)2＞Ba(NO3)2. In the reaction, Bi(NO3)3, which is impregnated on K-10, ha fast nitration rate and high yield and is easy to separate from the product by filtrati The methyl group in the pyrazole ring contributes to the nitration process, and the nit tion rate will increase with the number of methyl groups. (2) HNO3/H2SO4 system The HNO3/H2SO4 system usually has a strong nitration effect. Fischer et al. [ synthesized 4-chloropyrazole (9) using pyrazole as a raw material via chlorination re tion. Compound 9 was then dissolved in the concentrated H2SO4, and 100% HNO3 w slowly added below 40 °C. Then, the mixture was heated to 100 °C and stirred for 5 under reflux. After cooling to room temperature, the final solution was poured on crushed ice water and extracted with acetoacetic acid. The organic layers were wash with water, dried over magnesium sulfate, and dried under nitrogen to g 4-chloro-3,5-dinitro-1H-pyrazole (10) in a yield of 86.7%. The synthesis route is shown Scheme 7. The reaction is simple, no further purification is required, and the react yield is high. (3) HNO 3 /P 2 O 5 system Wang et al. [21] dissolved P 2 O 5 in fuming HNO 3 and then added (6-(3,5-dimethyl-1Hpyrazole-1-yl)-1,2,4-triazole[4,3-b]-1,2,4,5-tetrazine-3-amino (11) at 0 • C. The reaction mixture 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-3yl)nitramide (12) with a yield of 58%. In this reaction, the NH 2 in 1,2,4-triazol ring is also nitrated to NHNO 2 . The synthesis route is shown in Scheme 8. The nitrification system used in this reaction is HNO 3 /P 2 O 5 . P 2 O 5 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. 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/P2O5. P2O5 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. (1) 100% HNO3 system HNO3 is a strong nitration agent, it can be used to nitrate NH2 to NHNO2. Yin et al. [22] synthesized 1,1′-(ethane-1,2-diyl)bis(3,5-dinitro-)1H-pyrazole-4-amine) (14) using pyrazole as raw material through halogenation, nitration, neutralization, and alkylation reaction. Afterwards, compound 14 was added to 100% HNO3 in portions below 10 °C. The reaction was held for 10 min at 5 °C, and HNO3 was removed by blowing in air. The residue was dried under vacuum to give (15). The synthesis route is shown in Scheme 9. This process uses 100% HNO3 as the nitration system. For the nitration of different azole rings, different concentrations of HNO3 are required. (2) 70% HNO3/H2SO4 system Zhang et al. [23] added 4-amino-3,5-dinitropyrazole (16) to a mixture of HNO3 (70%) and concentrated H2SO4 in a volume ratio of 1:1 at 0 °C. The mixture was stirred for 2 h and then slowly warmed to room temperature. After stirring for another 4 h, the (1) 100% HNO 3 system HNO 3 is a strong nitration agent, it can be used to nitrate NH 2 to NHNO 2 . Yin et al. [22] synthesized 1,1 -(ethane-1,2-diyl)bis(3,5-dinitro-)1H-pyrazole-4-amine) (14) using pyrazole as raw material through halogenation, nitration, neutralization, and alkylation reaction. Afterwards, compound 14 was added to 100% HNO 3 in portions below 10 • C. 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 -[1,1 -(ethane-1,2-diyl)bis(3,5-dinitro-1Hpyrazole-4,1-diyl)]dinitramide (15). The synthesis route is shown in Scheme 9. This process uses 100% HNO 3 as the nitration system. For the nitration of different azole rings, different concentrations of HNO 3 are required.
(2) 70% HNO3/H2SO4 system Zhang et al. [23] added 4-amino-3,5-dinitropyrazole (16) to a mixture of HNO3 (70%) and concentrated H2SO4 in a volume ratio of 1:1 at 0 °C. The mixture was stirred for 2 h and then slowly warmed to room temperature. After stirring for another 4 h, the (2) 70% HNO 3 /H 2 SO 4 system Zhang et al. [23] added 4-amino-3,5-dinitropyrazole (16) to a mixture of HNO 3 (70%) and concentrated H 2 SO 4 in a volume ratio of 1:1 at 0 • C. The mixture was stirred for 2 h and then slowly warmed to room temperature. After stirring for another 4 h, the reaction mixture was poured into ice water and extracted with ether to obtain 4-nitroamino-3,5dinitropyrazole (17). The synthesis route is shown in Scheme 10. (3) HNO3/Ac2O system He et al. [23] synthesized 4-methylamino-3,5-dinitropyrazole (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 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 obtained by removing excess acid under vacuum with a yield of 95%. The synthesis route is shown in Scheme 11. This reaction uses HNO3/Ac2O as a nitration system, which is simple to operate, has no by-products, and the yield is as high as 95%. (3) HNO 3 /Ac 2 O system He et al. [23] synthesized 4-methylamino-3,5-dinitropyrazole (18) using 4-chloro-3,5dinitro pyrazole (10) as a raw material through nucleophilic substitution reaction. Firstly, 100% HNO 3 was slowly added to a cooled solution of compound 18 in acetic acid, after which Ac 2 O was added, and the mixture was stirred for 1.5 h at room temperature. 4-(Nmethylnitramino)-3,5-dinitropyrazole (19) was finally obtained by removing excess acid under vacuum with a yield of 95%. The synthesis route is shown in Scheme 11. This reaction uses HNO 3 /Ac 2 O as a nitration system, which is simple to operate, has no by-products, and the yield is as high as 95%.
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 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 obtained by removing excess acid under vacuum with a yield of 95%. The synthesis route is shown in Scheme 11. This reaction uses HNO3/Ac2O as a nitration system, which is simple to operate, has no by-products, and the yield is as high as 95%.
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 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 obtained by removing excess acid under vacuum with a yield of 95%. The synthesis route is shown in Scheme 11. This reaction uses HNO3/Ac2O as a nitration system, which is simple to operate, has no by-products, and the yield is as high as 95%.
Molecules 2022, 27, x FOR PEER REVIEW 7 of 20 stirred for 5 h at room temperature, filtered, and washed with water to obtain 1,1′,4,4′-tetranitro-1H,1′H-3,3′-dipyrazole (23). The synthesis route is shown in Scheme 13. NH4NO3/TFAA are used as nitration reagents to make reaction conditions mild, and post-treatment of waste acid is not needed at the end of the reaction. Yin et al. [27] cooled a concentrated H2SO4 suspension of 3,6-dinitropyrazole[4,3 pyrazole-1,4-diamine (24) to −15°C in an ice-salt bath, then fuming HNO3 was add dropwise to the mixture. After the mixture was stirred for 2 h at −15 ° N,N'- (3,6-dinitropyrazole[4,3-c] pyrazole-1,4-diyl)dinitramine (25) was obtained by tering the reaction solution and washing with TFAA. The synthesis route is shown Scheme 14. (1) 70% HNO3 system 3-nitro-1,2,4-triazol-5-one (NTO) is a kind of insensitive high-energy explosive w excellent comprehensive performance [28,29]. The more mature synthesis method NTO is by nitration of TO(1,2,4-triazol-5-one), which is synthesized from semicarbazi hydrochloride and formic acid using condensation and cyclization reaction. The synth sis route is shown in Scheme 15. The nitrating agent is 70% or 98% HNO3. Huang et [30] added TO to 70% HNO3 in batches at 60-65 °C, reacted for 1 h, then cooled to 3 °C an ice-water bath, filtered, and collected the HNO3 filtrate, which was recycled in t next batch of reactions. The filter cake was rinsed with water and followed by vacuu filtration. Finally, NTO was obtained via recrystallization from water with a yield 75.4% and a purity of 99.94%. Compared with the use of 98% HNO3 as the nitrati agent, this nitration method has a simpler process, safer operation, and HNO3 filtr can be reused, so the cost of raw materials can be lowered. (1) 70% HNO 3 system 3-nitro-1,2,4-triazol-5-one (NTO) is a kind of insensitive high-energy explosive with excellent comprehensive performance [28,29]. The more mature synthesis method of NTO is by nitration of TO(1,2,4-triazol-5-one), which is synthesized from semicarbazide hydrochloride and formic acid using condensation and cyclization reaction. The synthesis route is shown in Scheme 15. The nitrating agent is 70% or 98% HNO 3 . Huang et al. [30] added TO to 70% HNO 3 in batches at 60-65 • C, reacted for 1 h, then cooled to 3 • C in an ice-water bath, filtered, and collected the HNO 3 filtrate, which was recycled in the next batch of reactions. The filter cake was rinsed with water and followed by vacuum 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% HNO 3 as the nitrating agent, this nitration method has a simpler process, safer operation, and HNO 3 filtrate can be reused, so the cost of raw materials can be lowered.

Triazoles
A fuming HNO3/con. H2SO4 system can be used to nitrate -NH2 to NHNO2, which is connected with N in a pyrazole ring.

Triazoles
2.3.1. Nitrification of H on 1,2,4-Triazole Ring C (1) 70% HNO3 system 3-nitro-1,2,4-triazol-5-one (NTO) is a kind of insensitive high-energy explosive with excellent comprehensive performance [28,29]. The more mature synthesis method of NTO is by nitration of TO(1,2,4-triazol-5-one), which is synthesized from semicarbazide hydrochloride and formic acid using condensation and cyclization reaction. The synthesis route is shown in Scheme 15. The nitrating agent is 70% or 98% HNO3. Huang et al. [30] added TO to 70% HNO3 in batches at 60-65 °C, reacted for 1 h, then cooled to 3 °C in an ice-water bath, filtered, and collected the HNO3 filtrate, which was recycled in the next batch of reactions. The filter cake was rinsed with water and followed by vacuum 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. (2) HNO 3 /Ac 2 O system Aizikovich et al. [31] added 99% HNO 3 to Ac 2 O at 0 • C while stirring for 30 min. The solid N 3 ,N 6 -bis(1H-1,2,4-triazol-5-yl)-1,2,4,5-tetrazine-3,6-diamine (26) was slowly added to the mixture, after which, the solution was stirred for 2 h under anhydrous conditions. Then, the reaction solution was warmed to room temperature, filtered and washed quickly with TFAA, and immediately redissolved in hot CH 3 CN. The obtained CH 3 CN solution was heated for 30 min at 65 • C, then cooled to room temperature. Pure N 3 ,N 6 -bis(3-nitro-1H-1,2,4-triazole-5-yl)-1,2,4,5-tetrazine-3,6-diamine (28) was filtrated and washed with CH 3 CN to give a yield of 31%. The synthesis route is shown in Scheme 16. Although the yield of the reaction is low, the operation is simple with short reaction time, and the product does not need further purification. (2) HNO3/Ac2O system Aizikovich et al. [31] added 99% HNO3 to Ac2O at 0 °C while stirring for 30 min. The solid N 3 ,N 6 -bis(1H-1,2,4-triazol-5-yl)-1,2,4,5-tetrazine-3,6-diamine (26) was slowly added to the mixture, after which, the solution was stirred for 2 h under anhydrous conditions. Then, the reaction solution was warmed to room temperature, filtered and washed quickly with TFAA, and immediately redissolved in hot CH3CN. The obtained CH3CN solution was heated for 30 min at 65 °C, then cooled to room temperature. Pure N 3 ,N 6 -bis(3-nitro-1H-1,2,4-triazole-5-yl)-1,2,4,5-tetrazine-3,6-diamine (28) was filtrated and washed with CH3CN to give a yield of 31%. The synthesis route is shown in Scheme 16. Although the yield of the reaction is low, the operation is simple with short reaction time, and the product does not need further purification. acid and aminoguanidine bicarbonate as raw materials. After that, HNO 3 was slowly added to a concentrated H 2 SO 4 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 recrystallization from boiling water with a yield of 77%. The synthesis route is shown in Scheme 17.

Nitrification of H on 1,2,3-Triazole Ring N
Thottempudi et al. [37] added concentrated HNO 3 to Ac 2 O dropwise at −5 • C, the mixture was stirred for 30 min, and then stirred for another 45 min at room temperature. Subsequently, the mixture was cooled to −5 • C, and tris(triazolo) benzene (38) was added in portions, stirred for about 15 min, and stirred overnight at room temperature. The mixture was then poured onto ice, filtered, and washed with water to obtain the final product of trinitrotris(triazolo)benzene (39) with a yield of 53%. The synthesis route is shown in Scheme 22. Thottempudi et al. [37] added concentrated HNO3 to Ac2O dropwise at −5 °C, t mixture was stirred for 30 min, and then stirred for another 45 min at room temperatu Subsequently, the mixture was cooled to −5 °C, and tris(triazolo) benzene (38) was ad ed in portions, stirred for about 15 min, and stirred overnight at room temperature. T mixture was then poured onto ice, filtered, and washed with water to obtain the fin product of trinitrotris(triazolo)benzene (39) with a yield of 53%. The synthesis route shown in Scheme 22.    (40) in MeCN in an ice-water bath, and added nitronium tetrafluoroborate (NO 2 BF 4 ) 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 KBF 4 was removed by filtration and another equivalent of KOH in ethanol was added. The solvent was 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 remove KCl. After acetone was evaporated, the crude product was recrystallized from a small amount of methanol to yield colorless 42 (90%). The synthesis route is shown in Scheme 23. The reaction conditions are mild and the temperature is easy to control. However, HBF 4 must be removed after the reaction, the yield of compound 41 is low, and the purification is difficult.
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 by filtration and another equivalent of KOH in ethanol was added. The solvent was 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 remove KCl. After acetone was evaporated, the crude product was recrystallized from a small amount of methanol to yield colorless 42 (90%). The synthesis route is shown in Scheme 23. The reaction conditions are mild and the temperature is easy to control. However, HBF4 must be removed after the reaction, the yield of compound 41 is low, and the purification is difficult. (2) N2O5 system Fischer et al. [39] synthesized 1-methoxycarbonyl-1,5-diaminotetrazole (43) using dimethyl carbonate via nucleophilic substitution and a ring formation reaction. After that, compound 43 was suspended in anhydrous acetonitrile at 0 °C, a solution of N2O5 in acetonitrile (MeCN) was added, and the mixture was stirred for 1 h. KOH aqueous solution was then added dropwise, the aqueous phase was separated, and the water was evaporated under high vacuum. The residue was stirred in methanol for several hours. The reaction solution was filtered, washed with methanol, and dried. The obtained solid was dissolved in 2M HCl, and 1,5-bis(nitroamino)tetrazole (46) was obtained by extrac- (2) N 2 O 5 system Fischer et al. [39] synthesized 1-methoxycarbonyl-1,5-diaminotetrazole (43) using dimethyl carbonate via nucleophilic substitution and a ring formation reaction. After that, compound 43 was suspended in anhydrous acetonitrile at 0 • C, a solution of N 2 O 5 in acetonitrile (MeCN) was added, and the mixture was stirred for 1 h. KOH aqueous solution was then added dropwise, the aqueous phase was separated, and the water was evaporated under high vacuum. The residue was stirred in methanol for several hours. The reaction solution was filtered, washed with methanol, and dried. The obtained solid was dissolved in 2M HCl, and 1,5-bis(nitroamino)tetrazole (46) was obtained by extraction with ethyl acetate in a yield of 50%. The synthesis route is shown in Scheme 24. The reaction has less heat generation and the temperature is easy to control. Moreover, the product separation is simple with no waste acid treatment. (3) 100% HNO3 system Kumar et al. [40] synthesized amino 1-((1H-tetrazol-5-yl)methyl)-1H-tetrazole-5-amino (48) using aminoacetonitrile hydrochloride and cyanide azide (47) as raw materials through two-step ring formation reaction. 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 obtained by extraction with ethyl acetate in a yield of 65%. The synthesis route is shown in Scheme 25. (3) 100% HNO 3 system Kumar et al. [40] synthesized amino 1-((1H-tetrazol-5-yl)methyl)-1H-tetrazole-5-amino (48) using aminoacetonitrile hydrochloride and cyanide azide (47) as raw materials through two-step ring formation reaction. Then, compound 2 was slowly added to 100% HNO 3 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 obtained by extraction with ethyl acetate in a yield of 65%. The synthesis route is shown in Scheme 25. chloride and cyanide azide (47) as raw materials through two-step ring formation reaction. 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)  Klapçtke et al. [41] dissolved 1,5-diaminotetrazole in anhydrous acetonitrile at 0 °C and added NO2BF4 to the solution with stirring. The reaction mixture was then stirred overnight at room temperature. A pale yellow solid was obtained by evaporating acetonitrile under vacuum. The solid was re-dissolved in a small amount of ethanol, and then a mixed solution of KOH and ethanol was added to precipitate potassium tetrafluoroborate. Followed by filtration, the filtrate was evaporated and 5-amino-1-nitroaminotetrazole (HDATNO2, 50) was obtained with a yield of 59%. The synthesis route is shown in Scheme 26. The nitrating agent, NO2BF4, is environmentally friendly and 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. Klapçtke et al. [41] dissolved 1,5-diaminotetrazole in anhydrous acetonitrile at 0 • C and added NO 2 BF 4 to the solution with stirring. The reaction mixture was then stirred overnight at room temperature. A pale yellow solid was obtained by evaporating acetonitrile under vacuum. The solid was re-dissolved in a small amount of ethanol, and then a mixed solution of KOH and ethanol was added to precipitate potassium tetrafluoroborate. Followed by filtration, the filtrate was evaporated and 5-amino-1-nitroaminotetrazole (HDATNO 2 , 50) was obtained with a yield of 59%. The synthesis route is shown in Scheme 26. The nitrating agent, NO 2 BF 4 , is environmentally friendly and does not require waste acid treatment. The reaction conditions are mild and the temperature is easy to control. There are fewer byproducts in the reaction and the selectivity of the reaction is high, but NO 2 BF 4 is expensive and has high costs. (2) N2O5 system Fischer et al. [42] suspended 1,1′-diamino-5,5′-azobitetrazole (51) in at 0 °C and added a solution of N2O5 in cold acetonitrile dropwise. The was added dropwise until 1,1′-diamino-5,5′-azobitetrazole was dissolved red crystal of 1,1′-dinitroammonium-5,5′-azobitetrazole dipotassium sal tained via filtration. The yield was 62%. Subsequently, the salt 4 was d HCl, and a colorless single crystal of 1,1′-dinitroammonium-5,5′-azotetr obtained via extraction with ethyl acetate. The synthesis route is shown This reaction uses N2O5 as a nitration system, which has higher nitration side reactions, superior yield, and lower equipment requirements, thereb cost of the entire process. (2) N 2 O 5 system Fischer et al. [42] suspended 1,1 -diamino-5,5 -azobitetrazole (51) in dry acetonitrile at 0 • C and added a solution of N 2 O 5 in cold acetonitrile dropwise. The KOH solution was added dropwise until 1,1 -diamino-5,5 -azobitetrazole was dissolved, and then the red crystal of 1,1 -dinitroammonium-5,5 -azobitetrazole dipotassium salt (52) was obtained via filtration. The yield was 62%. Subsequently, the salt 4 was dissolved in 2M HCl, and a colorless single crystal of 1,1 -dinitroammonium-5,5 -azotetrazole (53) was obtained via extraction with ethyl acetate. The synthesis route is shown in Scheme 27. This reaction uses N 2 O 5 as a nitration system, which has higher nitration selectivity, less side reactions, superior yield, and lower equipment requirements, thereby reducing the cost of the entire process. (2) N2O5 system Fischer et al. [42] suspended 1,1′-diamino-5,5′-azobitetrazole (51) in dry acetonitr at 0 °C and added a solution of N2O5 in cold acetonitrile dropwise. The KOH soluti was added dropwise until 1,1′-diamino-5,5′-azobitetrazole was dissolved, and then t red crystal of 1,1′-dinitroammonium-5,5′-azobitetrazole dipotassium salt (52) was o tained via filtration. The yield was 62%. Subsequently, the salt 4 was dissolved in 2 HCl, and a colorless single crystal of 1,1′-dinitroammonium-5,5′-azotetrazole (53) w obtained via extraction with ethyl acetate. The synthesis route is shown in Scheme This reaction uses N2O5 as a nitration system, which has higher nitration selectivity, l side reactions, superior yield, and lower equipment requirements, thereby reducing t cost of the entire process.  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 mixture was stirred overnight. 5,5 -dinitroammonium-3,3 -azo-1,2,4-oxadiazole (55) was obtained via filtration and washed with TFAA, with a yield of 75%. The synthesis route is shown in Scheme 28. The reaction yield is high and the obtained product is pure without further purification. Scheme 27. Synthesis of 1,1′-dinitramino-5,5′-azobitetrazole [42].
(4) HNO3/Ac2O system 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) furazan-4-yl] methylene diamine (67) was obtained by filtering and washing the precipitate 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 procedures and a high yield.

Pyridazines
Nitrification of H on Pyridazine Ring C Gospodinov et al. [50] prepared the compound 3,5-dimethoxypyridazine-1-oxi (69) using dichloropyridazine as a raw material by substitution reaction and oxidati reaction, and then used two nitration systems to obtain compound 70. The synthe route is shown in Scheme 36. (1) 20% H2SO4/100% HNO3 system Compound 69 was dissolved in 20% fuming H2SO4 at 5 °C, after which, NaNO3 w added in batches, the reaction mixture was stirred for 1 h, and was then slowly warm up to room temperature. After that, the reaction mixture was stirred overnight at 60 Scheme 35. Synthesis of 3-nitramino-4-nitrofurazan [49].

Pyridazines
Nitrification of H on Pyridazine Ring C Gospodinov et al. [50] prepared the compound 3,5-dimethoxypyridazine-1-oxide (69) using 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.

Pyridazines
Nitrification of H on Pyridazine Ring C Gospodinov et al. [50] prepared the compound 3,5-dimethoxypyridazine-1-ox (69) using dichloropyridazine as a raw material by substitution reaction and oxidat reaction, and then used two nitration systems to obtain compound 70. The synthe route is shown in Scheme 36.
(1) 20% H2SO4/100% HNO3 system Compound 69 was dissolved in 20% fuming H2SO4 at 5 °C, after which, NaNO3 w added in batches, the reaction mixture was stirred for 1 h, and was then slowly warm up to room temperature. After that, the reaction mixture was stirred overnight at 60 and then poured onto crushed ice. The resulting suspension was stirred until the dissolved and the resulting precipitate was filtered. The crude product was dissolved conc. H2SO4, stirred for 3 h at 60 °C, and then poured on ice and the precipitate was (1) 20% H 2 SO 4 /100% HNO 3 system Compound 69 was dissolved in 20% fuming H 2 SO 4 at 5 • C, after which, NaNO 3 was added in batches, the reaction mixture was stirred for 1 h, and was then slowly warmed up to room temperature. After that, the reaction mixture was stirred overnight at 60 • C and then poured onto crushed ice. The resulting suspension was stirred until the ice dissolved and the resulting precipitate was filtered. The crude product was dissolved in conc. H 2 SO 4 , 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% H 2 SO 4 /100% NaNO 3 system Compound 69 was dissolved in 20-25% fuming H 2 SO 4 at 10 • C, and 100% HNO 3 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 and the obtained yellowish precipitate was filtered off and washed with water. The crude product was dissolved in conc. H 2 SO 4 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 compound 70 with concentrated ammonia in acetonitrile solution.

Pyrazines
Nitrification of H on Pyrazine Ring C The density of 2,6-diamino-3,5-dinitropyrazine-1-oxide (LLM-105, 73) is 1.92 g·cm −3 with the detonation velocity of 8516 m·s −1 and the detonation pressure of 35.9 GPa. It is a new explosive with excellent energy and safety performance. In the process of its preparation, there is a typical nitration reaction of H on pyrazine C, and the preparation method of LLM-105 has been improving. In 2014, Zhou et al. [51] used two nitration systems to nitrate the intermediate 2,6-diacetamidopyrazine-1-oxide (72) to obtain LLM-105. The synthesis route is shown in Scheme 37.
(1) 20% H2SO4/100% HNO3 system Compound 72 was added into 20% fuming H2SO4 when the temperature was than 25 °C, the temperature of the mixture was controlled to be lower than 10 °C end of feeding, and then fuming HNO3 was slowly added into the mixture. Afterw the system was controlled to react for 1 h within 10-15 °C and then heated to room perature for 2 h. Finally, the mixture was poured onto crushed ice, filtered, washe water, and dried to obtain the bright yellow LLM-105 solid with the yield of 72%.
(2) 100% HNO3/TMPSHSO4 system N,N,N-trimethyl-N-propanesulfonate-ammonium bisulfate (TMPSHSO4), as a ic liquid, was dissolved in fuming HNO3, cooled to about 0 °C, and then compou was slowly added. The reaction solution was stirred for 0.5 h; then heated to 25 acting for 1 h; and heated to 75 °C, reacting for 4 h. After the reaction was complete mixture was cooled to room temperature, diluted with distilled water, filtere washed with water three times, and dried to obtain yellow LLM-105, with a yi 68.4%. Compared with nitration with mixed acid, HNO3/acid ionic liquid has t vantages of simpler post-treatment and less waste acid discharge.
(1) 20% H 2 SO 4 /100% HNO 3 system Compound 72 was added into 20% fuming H 2 SO 4 when the temperature was lower than 25 • C, the temperature of the mixture was controlled to be lower than 10 • C at the end of feeding, and then fuming HNO 3 was slowly added into the mixture. Afterwards, the system was controlled to react for 1 h within 10-15 • C and then heated to room temperature for 2 h. Finally, the mixture was poured onto crushed ice, filtered, washed with water, and dried to obtain the bright yellow LLM-105 solid with the yield of 72%.
(2) 100% HNO 3 /TMPSHSO 4 system N,N,N-trimethyl-N-propanesulfonate-ammonium bisulfate (TMPSHSO 4 ), as an ionic liquid, was dissolved in fuming HNO 3 , cooled to about 0 • C, and then compound 72 was slowly added. The reaction solution was stirred for 0.5 h; then heated to 25 • C, reacting for 1 h; and heated to 75 • C, reacting for 4 h. After the reaction was completed, the mixture was cooled to room temperature, diluted with distilled water, filtered and washed with water three times, and dried to obtain yellow LLM-105, with a yield of 68.4%. Compared with nitration with mixed acid, HNO 3 /acid ionic liquid has the advantages of simpler post-treatment and less waste acid discharge.

Conclusions
The characteristics of the used nitration agents are listed in Table 1.
Molecules 2022, 27, x FOR PEER REVIEW

Conclusions
The characteristics of the used nitration agents are listed in Table 1.

Conclusions
The characteristics of the used nitration agents are listed in Table 1. The nitration ability is stronger than that of HNO 3 , 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 HNO 3 /H 2 SO 4 should be selected for nitration. The reaction conditions 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.

HNO 3 /Ac 2 O
Compared with the nitrating reagent HNO 3 /H 2 SO 4 , the HNO 3 /Ac 2 O mixture has a weaker nitrification ability, but the acid anhydride can effectively reduce the oxidation of HNO 3 .

NO 2 BF 4
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 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%. N 2 O 5 N 2 O 5 is a green nitrification reagent that can be used for the nitration of sensitive compounds. Compared with nitration reagents such as HNO 3 , HNO 3 /H 2 SO 4 , HNO 3 /acid anhydride, it has the following advantages: no need for waste acid treatment, the reaction has less heat release and 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 CH 2 Cl 2 as solvent, the temperature is generally from 20 • C to 100 • C, and the yield is about 90%. HNO 3 /P 2 O 5 In this system, P 2 O 5 is not only a dehydrating agent, but also a nitrification accelerator. The nitration system is suitable for the nitration of aromatics as well as amines.
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 nitrogenrich 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 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-1oxide (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 energetic 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 environmentally 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.; writingoriginal 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.