Unlocking the potential of pyridazine: a promising backbone for high-energy density compounds

Abstract

Nitrogen-rich heterocycles represent a significant class of backbone in energetic compounds, distinguished by their substantial nitrogen content and elevated heats of formation. These characteristics make them a crucial area of investigation in the ongoing quest to develop high-energy-density materials (HEDMs). Within this domain, azines, which are heterocyclic compounds incorporating two or more nitrogen atoms within their ring structure, have garnered increasing scholarly interest. Inherent structural design of pyridazine facilitates the strategic integration of multiple explosophoric groups, thereby amplifying their energetic capabilities. Among the azine derivatives, pyridazines, a specific type of diazine, typically exhibit resistance to direct nitration. However, they can effectively undergo electrophilic substitution when activated by potent electron-donating functionalities. A notable characteristic of pyridazines is their planar molecular configuration, which promotes efficient π–π stacking interactions. This intermolecular arrangement contributes to highly dense crystal packing, consequently yielding materials with superior densities.

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Introduction

Energetic materials (EMs) are essential components of modern weapons and military systems. They supply the energy required for these systems to operate, meaning their performance has a direct impact on the effectiveness and technological advancement of military equipment.^1,2 Due to their vital role in national defense, many countries continue to invest in the development of improved EMs. This ongoing need for high-performance EMs has also driven industrial progress in the field of explosives in recent years.³ The representative ancient high-energy-density materials (HEDMs) are black powder and nitroglycerine (NG), followed by first-generation HEDMs, including trinitrotoluene (TNT) and dynamite, while the second generation includes triaminotrinitrobenzene (TATB), cyclotrimethylenetrinitramine (RDX), and cyclotetramethylenetetranitramine (HMX). Contemporary research and development have yielded a third generation of HEDMs, exemplified by compounds such as hexanitrohexaazaisowurtzitane (CL-20) and octanitrocubane (ONC) (Fig. 1).^4,5 As a result of these advancements, the energy output of explosives and propellant components has seen substantial improvement.^6,7 However, this notable increase in detonation performance has also heightened global concerns about safety. In response, recent research in EMs has shifted toward the design and synthesis of new HEDMs that combine high energy with insensitivity, aiming to address the evolving requirements of modern military applications.⁸ With the increasing demand for HEDMs, new EMs are being developed using innovative concepts and methodologies.⁹ The most prominent backbones are five and six-membered heterocyclic compounds having two or more nitrogen atoms in the backbone.^10–16 These structures are characterized by a high number of energetic N–N bonds, along with a planar, conjugated framework that allows for electronic delocalization.^17–19 As a result, they offer several key advantages, including excellent density, elevated heat of formation (HOF), high molecular stability, and environmentally friendly detonation products.^20–23

Fig. 1 Advancement in the field of HEDMs and scope of research based on pyridazines.

These remarkable molecular frameworks, when combined with introduced explosophoric groups such as nitro, azido, nitramino, nitro ester, and others, further enhance the energetic properties of the materials.²⁴ These nitrogen-rich compounds derive their energy primarily from their high HOF, rather than through intramolecular oxidation of a carbon backbone, as seen in traditional explosives like TNT or pentaerythritol tetranitrate (PETN). The elevated energy content of HEDMs is largely attributed to the presence of adjacent nitrogen atoms, which readily convert into nitrogen gas (N₂) upon detonation.²⁵ The HOF in compounds is influenced by their ring structures and can be tuned by substituting hydrogen atoms with various energetic functional groups. These substitutions can markedly alter physical properties such as density, oxygen balance, thermal stability, HOF, sensitivity, and melting point. Ultimately, these changes can enhance the exothermic performance of combustion and detonation processes.^26,27 Considerable research has been directed toward azoles as key building blocks in energetic compounds. When these substituted azoles are combined with energetic anions, they form new energetic salts. These five-membered heterocycles are among the most widely used structures for the development of novel energetic salts and ionic liquids.^28–30 Recently, efforts to modify these rings with various substituents have advanced the design of new EMs. These systems offer multiple sites for the incorporation of explosophoric groups, thereby enhancing their potential as energetic compounds. Among the diazine isomers, pyridazine is particularly noteworthy due to its comparatively higher HOF (278.36 kJ mol⁻¹), surpassing that of pyrimidine (195.94 kJ mol⁻¹) and pyrazine (196.06 kJ mol⁻¹), thus highlighting its suitability for advanced energetic applications. Like other diazines, pyridazines are resistant to nitration and can undergo electrophilic substitution reactions when the ring is strongly activated by electron-donating groups.³¹ The planar geometry of pyridazine enables effective π–π stacking, promoting dense crystal packing resulting in high material density.

In recent years, the application of self-assembly strategies to modulate the properties of pyridazine-based EMs has garnered considerable interest, primarily due to their operational simplicity and environmentally benign nature.^32,33 This strategy illustrates the efficacy of self-assembly in tailoring the sensitivity of EMs.³⁴ Numerous energetic compounds featuring molecular perovskite structures through the self-assembly strategy were designed and synthesized.³⁵ Consequently, this approach holds significant promise for advancing the development of energetic materials by offering a straightforward and efficient synthetic route. This review highlights recent advances in the field, with a particular emphasis on pyridazine-based nitrogen-rich heterocycles and the synthetic strategies employed to incorporate “explosophore” groups into these heterocyclic structures. It offers a thorough comparison and discussion of synthetic methodologies and the overall research idea. Additionally, the review aims to shed light on the intriguing chemistry and potential applications of pyridazine-based HEDMs.

Monocyclic pyridazine compounds

Developing EMs that exhibit both powerful detonation capabilities and desirable safety characteristics, such as insensitivity towards mechanical stimuli and high thermal stability, is a complex and ongoing challenge. To overcome these difficulties, researchers have explored several molecular design strategies. One common approach involves introducing conjugated systems, which can enhance stability through electron delocalization and aromaticity.³⁶ Another widely used method is the formation of nitrogen-rich salts, which not only increase the nitrogen content, contributing to a higher energy output, but also improve thermal stability and reduce sensitivity. Additionally, the strategic inclusion of alternating amino (NH₂), nitro (NO₂), and N-oxide (N⁺–O⁻) groups has been shown to significantly influence the material's structural and energetic properties.³⁷ These functional groups often participate in the formation of both intra- and intermolecular hydrogen bonds, which help to stabilize the material by reinforcing its molecular framework. Notably, the incorporation of the N-oxide moiety has a dual benefit: it elevates the density and oxygen balance, which are key factors in improving overall energetic performance (Table 1).

Table 1 Physicochemical properties of benchmark explosives

Compounds	T d [°C]	ρ [g cm^−3]	HOF^c [kJ mol^−1]	VOD^d [m s^−1]	DP^e [GPa]	IS^f [J]	FS^g[N]
a T d: onset thermal decomposition temperature. b ρ: gas pycnometer density at room temperature. c HOF: computed solid-state heats of formation. d VOD: detonation velocity calculated using Explo-5. e DP: detonation pressure calculated using Explo-5. f IS: impact sensitivity. g FS: friction sensitivity.
TNT^36	300	1.65	−59.3	6820	19.4	39.2	353
RDX^38	205	1.80	86.0	8803	33.8	7.5	120
HMX^39	280	1.91	74.8	9144	39.2	7	120
FOX-7^40	220	1.85	−134.0	8613	31.6	24.7	>360
TATB^41	350	1.93	−139.7	8179	30.5	50	>360
DDNP^41	157	1.72	321.0	6900	24.7	1	24.7
CL-20^36	210	2.05	397.8	9706	45.2	4	94
LA^41	315	4.80	450.1	5920	33.8	2.5–4	0.1–1

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In 2018, Klapötke and co-workers reported the synthesis of 3,5-dimethoxypyridazine (5) from 2,2,2-trichloroethane-1,1-diol (1). Further, 5 was nitrated and N-oxidised. The attempts to get 3,5-dimethoxy-4,6-dinitropyridazine (8) using nitrating conditions from 5 and 7 failed due to the low nucleophilicity after mono-nitration.⁴² The di-nitration of 6 was carried out using 100% nitric acid and oleum to get 3,5-dimethoxy-4,6-dinitropyridazine-1-oxide (9). Various nucleophiles were further employed to substitute the methoxy group to get energetic compounds (9–14) with balanced properties. The nitration of 14 using 100% HNO₃ to get nitro ester substituted 15 was unsuccessful (Scheme 1).⁴³

Scheme 1 Pyridazine-based monocyclic HEDMs.

The physicochemical properties of all the synthesized EMs were evaluated. The thermal stability of compounds 9–14 ranges from 120–250 °C, and their detonation velocity (VOD) ranges from 6994 to 8486 m s⁻¹ with moderate sensitivities (Table 2).

Table 2 Physicochemical properties of monocyclic pyridazine-based energetic materials 9–14

Compounds	T d [°C]	ρ [g cm^−3]	HOF^c [kJ mol^−1]	VOD^d [m s^−1]	DP^e [GPa]	IS^f [J]	FS^g [N]
a T d: onset thermal decomposition temperature. b ρ: gas pycnometer density at room temperature. c HOF: computed solid-state heats of formation. d VOD: detonation velocity calculated using Explo-5. e DP: detonation pressure calculated using Explo-5. f IS: impact sensitivity. g FS: friction sensitivity.
9	151	1.59	−114.0	7227	20.8	20	360
10	250	1.63	102.7	7365	20.4	10	360
11	120	1.68	298.3	8276	29.1	5	120
12	215	1.84	110.0	8486	30.2	18	360
13	217	1.54	156.4	6994	17.6	30	360
14	170	1.69	−250.8	7389	20.2	8	360

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Bicyclic fused pyridazine compounds

Fused cyclic EMs, a unique class of large conjugate structures containing two or more rings that share two atoms and the bond between the rings, have demonstrated promising potential in the field of HEDMs. These compounds with a coplanar polycyclic structure exhibit considerably high HOF and ring-strain energy stored in the molecules and show obvious physicochemical characteristics with increased safety of the synthesis, transfer, and storage of HEDMs.⁴⁴ Therefore, pyridazine-based fused moieties have attracted significant attention, highlighting a new avenue to develop novel HEDMs with balanced detonation properties and sensitivity parameters. A unique strategy to substitute the pyridazine backbone with explosophore groups via a peripheral editing approach helps to synthesize several novel bicyclic fused EMs with excellent properties. As outlined in Scheme 2, commercially available 3,6-dichloropyridazin-4-amine (16) underwent nitration followed by amination and azidation with NaN₃ to yield 7-nitrotetrazolo[1,5-b]pyridazine-6,8-diamine (19), which was subsequently oxidized using HOF·CH₃CN to afford 6,7-dinitrotetrazolo[1,5-b]pyridazin-8-amine (20).⁴⁵ Additionally, 6-chloro-3-hydrazineylpyridazin-4-amine (22) was synthesized from 16 which was further reacted with trifluoroacetic acid to yield 6-chloro-3-(trifluoromethyl)-[1,2,4]triazolo[4,3-b]pyridazin-8-amine (23), followed by nitration to afford nitro substituted 6-chloro-7-nitro-3-(trifluoromethyl)-[1,2,4]triazolo[4,3-b]pyridazin-8-amine (24). Subsequent nucleophilic substitutions produced energetic salts 25–27.⁴⁶

Scheme 2 Triazole and tetrazole fused pyridazine-based bicyclic HEDMs.

Additionally, 22 underwent diazotization to form fused tetrazole compound 28, which, upon nitration followed by substitution, formed tetrazolo[1,5-b] pyridazine-based compounds 30 and 31 in good yields.

Additionally, Zhang and co-workers reported cyclisation of 3-chloro-6-hydrazineyl-5-nitropyridazin-4-amine (32) with cyanogen bromide in a mixed solvent afforded 6-chloro-8-nitro-[1,2,4]triazolo[4,3-b]pyridazine-3,7-diamine (33). Subsequent oxidation selectively transformed the amino group into a nitro group to yield 6-chloro-3,8-dinitro-[1,2,4]triazolo[4,3-b]pyridazin-7-amine (34). Further amination and azidation reactions were carried out to obtain 35 and 36, respectively.⁴⁰

Favourable properties of 19 include high insensitivities, detonation performance (VOD: 8899 m s⁻¹; DP: 30.3 GPa), and commendable thermal stability (T_d: 287 °C), affirming its potential as a heat-resistant explosive. Furthermore, tetrazole-substituted fused compounds 30 and 31 exhibit good detonation properties (VOD: 8830, 8837 m s⁻¹; DP: 29.8, 31.4 GPa), along with elevated insensitivity, highlighting their potential as advanced secondary explosives as depicted in Table 3. In the pursuit of heat-resistant EMs, 8-bromo-6-chloroimidazo[1,2-b] pyridazine (37) was treated with sodium methoxide to yield 6-chloro-8-methoxyimidazo[1,2-b]pyridazine (38), followed by nitration to obtain 6-chloro-8-methoxy-3,7-dinitroimidazo[1,2-b]pyridazine (39). Amination under varying pressures led to yield 6-chloro-3,7-dinitroimidazo[1,2-b]pyridazin-8-amine (40) and 3,7-dinitroimidazo[1,2-b]pyridazine-6,8-diamine (41).⁴⁷ Furthermore, in 2022, Zhang and co-workers applied similar strategies with 17 and produced tetrazolo[1,5-b]pyridazine derivatives 2-((8-amino-7-nitrotetrazolo[1,5-b]pyridazin-6-yl)amino)ethan-1-ol (43), N6-methyl-7-nitrotetrazolo[1,5-b]pyridazine-6,8-diamine (46), and N3-(2-((5,6-diamino-4-nitropyridazin-3-yl)amino)ethyl)-5-nitropyridazine-3,4,6-triamine (49). These compounds were further nitrated to form 2-((8-amino-7-nitrotetrazolo[1,5-b]pyridazin-6-yl)amino)ethyl nitrate (44), N-(8-amino-7-nitrotetrazolo[1,5-b]pyridazin-6-yl)-N-methylnitramide (47), and N-(5,6-diamino-4-nitropyridazin-3-yl)-N-(2-((4,6-diamino-5-nitropyridazin-3 yl)(nitro)amino) ethyl) nitramide (50), highlighting the efficiency and adaptability of the synthetic routes (Scheme 3).⁴⁸ Among all, 41 and 49 demonstrate an exceptional decomposition temperature (T_d: 324, 303 °C), comparable to the benchmark heat-resistant explosive HNS (T_d: 318 °C), making them excellent heat-resistant explosives. Compounds 44, 47, and 50⁴⁸ exhibit excellent detonation performances (VOD: 8407–8665 m s⁻¹; DP: 28.7–33 GPa), low sensitive (IS: 18–>40; FS: 112–360 N), considered as high energy explosives, underscoring the critical role of pyridazine-based fused backbone in multipurpose real-world applications (Table 4).

Scheme 3 Imidazole, tetrazole, and pyridazine-based fused bicyclic HEDMs.

Table 3 Physicochemical properties bicyclic compounds 19–36

Compounds	T d [°C]	ρ [g cm^−3]	HOF^c [kJ mol^−1]	VOD^d [m s^−1]	DP^e [GPa]	IS^f [J]	FS^g [N]
a T d: onset thermal decomposition temperature. b ρ: gas pycnometer density at room temperature. c HOF: computed solid-state heats of formation. d VOD: detonation velocity calculated using Explo-5. e DP: detonation pressure calculated using Explo-5. f IS: impact sensitivity. g FS: friction sensitivity.
19	287	1.86	398	8899	30.3	>40	>360
20	202	1.88	470	9021	34.8	18	112
25	274	1.82	−357.49	6876	17.9	>40	>360
26	229	1.87	−234.65	7306	21.1	>40	>360
27	217	1.90	−344.76	7503	23.7	>40	>360
30	215	1.86	537.41	8830	29.8	28	>360
31	203	1.91	426.58	8837	31.4	25	>360
35	234	1.93	348	8994	34.1	20	>360
36	217	1.84	684	8819	32.4	18	360

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Table 4 Physicochemical properties of compounds 41–63

Compounds	T d [°C]	ρ [g cm^−3]	HOF^c [kJ mol^−1]	VOD^d [m s^−1]	DP^e [GPa]	IS^f [J]	FS^g [N]
a T d: onset thermal decomposition temperature. b ρ: gas pycnometer density at room temperature. c HOF: computed solid-state heats of formation. d VOD: detonation velocity calculated using Explo-5. e DP: detonation pressure calculated using Explo-5. f IS: impact sensitivity. g FS: friction sensitivity.
41	324	1.85	158.45	8336	27.25	40	350
44	161	1.75	406	8407	29.3	—	—
47	201	1.77	481	8496	28.7	18	112
49	303	1.84	908	8809	29.3	>40	>360
50	199	1.80	1075	8665	33	>40	>360
52at	163	1.82	811.2	8746	31.5	5	120
54	290	1.80	446.5	8434	27.7	>40	>360
55	140	1.84	538	8926	33.7	—	—
62	292	1.87	1079	9064	35.2	16	>360
63	260	1.77	1235	8429	27.8	4	160

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In 2020, Shreeve and co-workers explored the priming capability of pyridazine-based moieties. In this study, azidation reaction on 17 yielded 52, which existed solely in the azido-tetrazole tautomeric form (52at), as confirmed by single-crystal X-ray analysis. Further, 32 underwent diazotisation followed by subsequent treatment with ammonia, yielding 8-nitrotetrazolo[1,5-b] pyridazine-6,7-diamine (54), which upon nitration yielded 55.^41,49,50 Additionally, on treatment of 17 and 32, yield hydrazo-bridged 6,6′-(hydrazine-1,2-diyl) bis(3-chloro-5-nitropyridazin-4-amine) (61), followed by cyclization with NaN₃ in dimethylformamide (DMF) to form 6,6′-(hydrazine-1,2-diyl)bis(7-nitrotetrazolo[1,5-b]pyridazin-8-amine) (62). Further dehydrogenation with NBS produced (E)-6,6′-(diazene-1,2-diyl) bis(7-nitrotetrazolo[1,5-b] pyridazin-8-amine) (63)⁵¹ (Scheme 4).

Scheme 4 Bridged and fused pyridazine-based bicyclic HEDMs.

52at exhibits exceptional detonation performance (VOD: 8746 m s⁻¹, DP: 31.5 GPa). Its high efficacy highlights its potential as a green primary explosive. Additionally, 54 exhibits excellent thermal stability (T_d: 290 °C), low sensitivity, and strong detonation properties, showing promise as a robust secondary explosive. Interestingly, 62 demonstrates remarkably high decomposition temperature (T_d: 292 °C) and low sensitivities (Table 4), highlighting its potential as a heat-resistant explosive. In contrast, 63 exhibits elevated sensitivities due to the absence of stabilizing intramolecular hydrogen bonding, highlighting its potential as a primary explosive. In the quest for fused imidazole-pyridazine-based HEDMs, Shreeve and coworkers explored commercially available 2-amino-4,5-dicyanoimidazole (64) treated in 1,4-dioxane, followed by DMF and hydrazine hydrate to yield 1H-imidazo[4,5-d] pyridazine-2,4,7-triamine (65).

Oxidation with KMnO₄/HCl gave 7-((2,7-diamino-1H-imidazo[4,5-d] pyridazin-4-yl)diazenyl)-1H-imidazo[4,5-d]pyridazine-2,4-diamine (68).

Further, by reacting 65 with perchloric acid at room temperature, two different polymorphs (α-4, β-4) were obtained on varying the solvent.⁵² The β-4 polymorphs show lower sensitivity towards mechanical stimuli, with a decrease in density and performance than their α-4 polymorph. α-4 and β-4 polymorphs have the VOD of 8437 and 8128 m s⁻¹ and density of 1.93 and 1.88 g cm⁻³ respectively.⁵¹ Nitration of 65 and 68 with 100% nitric acid produced nitrimino-substituted fused pyridazine-based compounds 66 and 69. Further reaction with NH₂OH·H₂O gave salts 67, 70.³⁹ Additionally, 4,5-dicyanoimidazole (71) was reacted with hydrazine monohydrate in isopropanol, followed by cyclisation with acetic acid to give 1H-imidazo[4,5-d]pyridazine-4,7-diamine (73), which on further nitration produced (Z)-N-(7-(nitroamino)-3,5-dihydro-4H-imidazo[4,5-d]pyridazin-4-ylidene)nitramide (74). Later, treatment with several bases yields energetic salts (75–79).⁵³ Furthermore, 2-nitro-4,5-dicyanoimidazole (80) was reacted with hydrazine monohydrate using acetic acid as a catalyst to form an intermediate, which was refluxed to yield 2-nitro-1-imidazo[4,5-d] pyridazine-4,7-diamine (82). Azo-coupling reaction was performed with 82, yielded 7-((7-amino-2-nitro-1H-imidazo[4,5-d] pyridazin-4-yl)diazenyl)-2-nitro-1H-imidazo[4,5-d]pyridazin-4-amine (87). Nitration of 82 and 87 with 100% nitric acid yielded 83 and 88 (Scheme 5).⁵⁴ Among the aminoimidazole fused series, the hydroxylammonium salt (67), exhibiting outstanding VOD (9203 m s⁻¹) and acceptable sensitivities, is comparable to HMX. Furthermore, 77, 85, and 86 exhibit excellent VOD (8782–8964 m s⁻¹) with low sensitivities, comparable to RDX (Table 5). This series of compounds highlights the design objectives for full-nitramino HEDMs, achieving a harmonious balance between energy and safety.

Scheme 5 Fused imidazole-pyridazine-based bicyclic HEDMs.

Table 5 Physicochemical properties of compounds 66–77

Compounds	T d [°C]	ρ [g cm^−3]	HOF^c [kJ mol^−1]	VOD^d [m s^−1]	DP^e [GPa]	IS^f [J]	FS^g [N]
a T d: onset thermal decomposition temperature. b ρ: gas pycnometer density at room temperature. c HOF: computed solid-state heats of formation. d VOD: detonation velocity calculated using Explo-5. e DP: detonation pressure calculated using Explo-5. f IS: impact sensitivity. g FS: friction sensitivity.
65.ClO4 -α-4	274	1.93	120.8	8437	32.86	14	168
65.ClO4 -β-4	272	1.88	−47.58	8128	29.40	20	144
66	116	1.86	349.6	8729	33.2	8	20
67	192	1.86	490.1	9203	37.6	24	160
69	117	1.81	530.2	9031	32.5	18	240
70	191	1.80	634.5	8701	31.6	30	240
74	166	1.82	355.2	8360	29.0	32	120
76	212	1.75	412.8	8425	27.8	24	240
77	228	1.78	561.4	8782	30.6	16	120
78	199	1.78	461.3	8673	31.1	18	160
83	117	1.80	407.8	8568	31.5	7	160
84	218	1.77	301.7	8599	30.0	32	>360
85	171	1.81	619.2	8964	33.4	36	160
86	142	1.79	429.0	8867	34.4	32	240
88	123	1.79	258.8	8263	28.6	40	360

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4,7-Diaminopyridazino[4,5-c] furoxan (93) was synthesized via a multi-step route starting from 2-cyanoacetic acid (89). Subsequent oxidation attempts with HOF and a H₂O₂/trifluoroacetic anhydride (TFAA) mixture led to unexpected products, including fused heterocycles, 7-nitro-[1,2,5]oxadiazolo[3,4-c]pyridazin-6-amine (94), 6-amino-7-nitro-[1,2,5]oxadiazolo[3,4-c]pyridazine 4-oxide (95), and trifluoroacetate salt of 4,7-diamino-[1,2,5]oxadiazolo[3,4-d]pyridazine-6-ium 1-oxide (96), highlighting a novel oxidative rearrangement pathway during the synthesis process.⁵⁴

Furthermore, in 2021, Shreeve and co-workers explored a fused pyridazine backbone to synthesize high-performance secondary explosives. The synthesis incorporates 4,5-dicyanotriazole (97) as starting material, which reacts with hydrazine in DMF at 80 °C to form 1H-[1,2,3] triazolo[4,5-d]pyridazine-4,7-diamine (99). Azo coupling of 99 yields 7-((7-amino-1H-[1,2,3] triazolo[4,5-d]pyridazin-4-yl)diazenyl)-1H-[1,2,3]triazolo[4,5-d]pyridazin-4-amine (105). Nitration of 99 and 105 using 100% nitric acid produces nitramino and nitrimino substituted fused moieties 100 and 106, respectively. Further, 100 react with energetic bases to afford three energetic salts (101–103), and 106 reverts to 105 upon treatment with base⁵⁵ (Scheme 6). Several substitution reactions were also performed on 29 to enhance its stability and performance, yielding 107–111(Scheme 7).⁵⁶ Furthermore, compound 96 surpassed TATB in performance while maintaining insensitivities. Owing to strong intermolecular interactions, 102, 103, and 111 exhibit impressive detonation velocities (9307–9351 m s⁻¹) and insensitivities, underscoring their strong potential for application as a high-energy, low-sensitivity explosive material (Table 6). This series of compounds highlights the importance of a versatile synthetic strategy to offer a promising approach for the design of novel fused-ring systems. In 2025, Srinivas and co-workers explored bicyclic fused pyridazine-based EMs in the quest to synthesise metal-free primary explosives. Ethyl 2-(6-chloro-[1,2,4] triazolo[4,3-b]pyridazin-3-yl)acetate (112) was synthesized via cyclization of 59 with ethoxyiminopropionate, followed by nitration to synthesis 6-chloro-3-(trinitromethyl)-[1,2,4]triazolo[4,3-b]pyridazine (113). Subsequent treatment with nitrogen-rich bases yields salts 114–116. Compound 59, upon further treatment with CNBr, which is upon nitration followed by hydrazine treatment, afforded 124 through nitro group displacement (Scheme 8).^57,58

Scheme 6 Fused furoxan, triazole, tetrazole, and pyridazine-based bicyclic HEDMs.

Scheme 7 Fused tetrazole and pyridazine-based bicyclic HEDMs.

Scheme 8 Fused 1,2,4-triazole and pyridazine-based bicyclic HEDMs.

Table 6 Physicochemical properties of compounds 94–102

Compounds	T d [°C]	ρ [g cm^−3]	HOF^c [kJ mol^−1]	VOD^d [m s^−1]	DP^e [GPa]	IS^f [J]	FS^g [N]
a T d: onset thermal decomposition temperature. b ρ: gas pycnometer density at room temperature. c HOF: computed solid-state heats of formation. d VOD: detonation velocity calculated using Explo-5. e DP: detonation pressure calculated using Explo-5. f IS: impact sensitivity. g FS: friction sensitivity.
94	186	1.79	417.8	8396	29.4	>50	>360
95	175	1.84	268.7	8695	32.9	36	>360
100	162	1.87	303.0	8875	34.5	18	120
101	210	1.77	490.3	8900	31	12	160
102	211	1.78	826.5	9351	34.5	7	120
103	178	1.83	615.8	9307	37.4	8	160
106	151	1.73	−27.5	—	—	>32	>240
107	217	1.85	639.45	8684	30.6	>60	>360
108	275	1.88	777.46	8595	30.0	>60	>360
109	281	1.85	739.55	8327	27.4	>60	>360
110	288	1.88	1121.23	8514	29.0	16	>360
111	239	1.73	950.17	9121	30.1	>60	>360

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Compounds 113, 122 exhibit high VOD and low sensitivity, highlighting their potential as metal-free primary explosives. Additionally, 121 and 123 demonstrate exceptional thermostability (T_d: 300, 353 °C), affirming their promise as a superior heat-resistant explosive (Table 7).

Table 7 Physicochemical properties of compounds 113–124

Compounds	T d [°C]	ρ [g cm^−3]	HOF^c [kJ mol^−1]	VOD^d [m s^−1]	DP^e [GPa]	IS^f [J]	FS^g [N]
a T d: onset thermal decomposition temperature. b ρ: gas pycnometer density at room temperature. c HOF: computed solid-state heats of formation. d VOD: detonation velocity calculated using Explo-5. e DP: detonation pressure calculated using Explo-5. f IS: impact sensitivity. g FS: friction sensitivity.
113	126	1.84	−156.31	7188	20.43	2.5	254
114	194	1.80	−4.14	7025	18.48	25	360
115	156	1.73	−92.8	6798	17.60	10	360
116	197	1.79	−142.7	6624	16.35	20	360
118	128	1.75	1028	7578	22.0	3	240
121	300	1.76	1042	8104	21.7	40	360
122	171	1.71	1598	7203	18.5	2.5	120
123	353	1.77	377.67	6710	17.68	40	360
124	183	1.60	565.5	7554	20.34	40	360

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Tricyclic fused pyridazine compounds

Tricyclic fused ring systems remain comparatively underexplored despite their potential to further enhance performance metrics. The limited advancement in this area can be largely ascribed to the inherent challenges associated with the cyclization of bridged bicyclic intermediates, a key step in the construction of such complex architectures.⁵⁹ These difficulties significantly constrain the skeletal diversity and hinder the development of efficient and versatile synthetic methodologies, thereby impeding the broader application and study of tricyclic fused energetic compounds.⁶⁰ The synthesis of tricyclic fused pyridazine-based energetic material was reported by Yang and co-workers using 3,6-dichloropyridazin-4-amine (16) as the starting material. The cyclisation followed by nitration led to the formation of 6-chloro-7-nitro-[1,2,4] triazolo[4,3-b]pyridazin-8-amine (125), which on treatment with phenyliodinediacetate (PIDA) forms the furoxan ring by the reaction of adjacent amino and nitro functionality. Interestingly, the formation of 125 was obtained back on treatment of 4-chloro-[1,2,5] oxadiazolo[3,4-d][1,2,4]triazolo[4,3-b]pyridazine 3-oxide (126) with aq. NH₃.

The chlorine atom in 126 was further substituted with an azide group and later reduced to an amine using Staudinger reduction (Scheme 9).⁶¹ Compounds 127 and 128 exhibit favourable thermal decomposition temperatures of 184 °C and 195 °C, respectively, along with high detonation velocities of 8644 and 8817 m s⁻¹ (Table 8). The cyclisation of 7-hydrazineyl-1H-pyrazolo[3,4-d]pyridazine-3,4-diamine (129) using cyanogen bromide and further oxidation led to the formation of dinitro-based tricyclic compound 6,7-dinitro-9H-pyrazolo[3,4-d][1,2,4]triazolo[4,3-b]pyridazin-3-amine (132).³⁸ Tricyclic based self-assembled EMs were also synthesized using perchloric acid as an oxidizer (133–137) (Scheme 10).⁶²

Scheme 9 Synthesis of tricyclic fused pyridazine-based HEDMs.

Scheme 10 Synthesis of fused tricyclic pyridazine-based HEDMs from cyanoimidazole.

Table 8 Physicochemical properties of compounds 127–137

Compounds	T d [°C]	ρ [g cm^−3]	HOF^c [kJ mol^−1]	VOD^d [m s^−1]	DP^e [GPa]	IS^f [J]	FS^g[N]
a T d: onset thermal decomposition temperature. b ρ: gas pycnometer density at room temperature. c HOF: computed solid-state heats of formation. d VOD: detonation velocity calculated using Explo-5. e DP: detonation pressure calculated using Explo-5. f IS: impact sensitivity. g FS: friction sensitivity.
127	184	1.77	1177.30	8644	30.90	7	108
128	195	1.93	501.30	8817	32.00	40	128
132	202	1.85	434.70	8440	28.80	25	360
133	336	1.94	733.40	8820	36.20	30	360
134	358	1.76	26.20	6996	15.02	40	360
135	322	1.88	−60.25	8056	19.98	20	216
136	421	1.78	36.10	7105	16.10	40	360
137	310	1.93	−44.16	8329	23.16	40	240

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Self-assembly

The self-assembly strategy for the construction of EMs involves the dissolution of multiple components in a specific solvent, followed by the controlled evaporation of the solvent. This approach presents a facile and efficient synthetic route for the development of advanced energetic compounds.⁶³ The self-assembly process is primarily governed by non-covalent interactions, such as hydrogen bonding and π–π stacking, necessitating the rational selection of molecular components to ensure successful assembly.⁵² In this context, energetic molecules and oxidizing agents, specifically H₂O₂, HNO₃, and HClO₄, are strategically employed as assembly constituents. Incorporation of oxidants enhances the energetic performance of the resulting molecular assemblies.

In 2021, Zhang and co-workers reported the fused 7-nitrotetrazolo[1,5-b]pyridazine-6,8-diamine (19)⁴⁵ based self-assembly utilizing hydrogen peroxide as oxidant (Scheme 11).⁶⁴ They also reported fused furoxan-pyridazine-based self-assembly utilising 4,7-diamino-[1,2,5]oxadiazolo[3,4-d]pyridazine 1-oxide (93)⁶⁵ with nitric acid and perchloric acid as oxidants. Further, the specific impulses of 138–141 were calculated by the NASA Chemical Equilibrium with Applications (CEA) program, offering better performance in comparison to RDX (275 s), HMX (274 s), and CL-20 (278 s) (Table 9). The specific impulse of 138 and 139 was found to be better than ammonium perchlorate (260 s). Later, 2H-[1,2,3]triazolo[4,5-d]pyridazine-4,7-diamine was treated with perchloric acid to get 141.⁶⁶ The near laser ignition test was carried out for 141, which showed excellent ignition and deflagration to detonation transition. The VODs for 138–141 vary from 8238 to 9339 m s⁻¹ while their DPs range from 29.40 to 42.50 GPa.

Scheme 11 Synthetic route for compounds 138–141.

Table 9 Physicochemical properties of compounds 138–141

Compounds	T d [°C]	ρ [g cm^−3]	HOF^c [kJ mol^−1]	VOD^d [m s^−1]	DP^e [GPa]	IS^f [J]	FS^g [N]	I sp [s]
a T d: onset thermal decomposition temperature. b ρ: gas pycnometer density at room temperature. c HOF: computed solid-state heats of formation. d VOD: detonation velocity calculated using Explo-5. e DP: detonation pressure calculated using Explo-5. f IS: impact sensitivity. g FS: friction sensitivity. h Specific impulse.
138	184	1.83	587.8	9166	37.30	10	120	291
139	181	1.94	872.6	9339	42.50	8	96	308
140	173	1.82	550.3	9051	33.10	12	128	256
141	280	2.01	−40.6	8238	35.60	10	120	233

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Conclusions and future directions

Research into pyridazine-based energetic frameworks has surged over the last few years, with a significant increase in the number of publications focusing on the synthesis and applications, which underscores the profound interest and escalating importance of this domain within the chemical and materials science communities. These frameworks present compelling advantages when compared to conventional EMs, notably their structural tunability, straightforward synthetic procedures, and enhanced stability. Despite the considerable advancements achieved thus far, there remains substantial untapped potential for further optimizing the overall performance of these energetic frameworks. Future endeavours could strategically focus on several key areas. Firstly, facilitating metal coordination within these structures could open new avenues for energetic property modulation. Secondly, the deliberate incorporation of ample hydrogen bond donor and acceptor units could significantly enhance intermolecular interactions and material stability. Lastly, promoting sophisticated self-assembly strategies could enable a higher degree of structural control and facilitate the judicious incorporation of oxidizers, thereby leading to an increased oxygen content, a critical factor for improved energetic performance.

Author contributions

Parasar Kumar: formal analysis; writing – original draft, writing – review & editing. Shreyasi Banik: formal analysis; writing – original draft, writing – review & editing. Srinivas Dharavath: funding acquisition; project administration; writing – original draft; writing – review & editing.

The manuscript was written through the contributions of all authors. All authors have given approval to the final version of the manuscript.

Conflicts of interest

The authors declare no competing financial interest.

Data availability

No primary research results, software, or code have been included, and no new data were generated or analysed as part of this review.

Acknowledgements

PK thanks IIT Kanpur for the fellowship and infrastructure. SB thanks UGC India for senior research fellowship and IIT Kanpur for infrastructure. SD is grateful for the financial support from the Core research grant (ANRF-CRG/2023/000007), The Anusandhan National Research Foundation-Science and Engineering Research Board, Department of Science and Technology, Government of India.

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Footnote

† These authors contributed equally.

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