Fused pyrazolo[3,4-d] pyrimidine nitrogen-rich salts with balanced energetic performance

Abstract

In this study, a series of novel energetic salts were synthesized and characterized using a pyrazolo[3,4-d]pyrimidine-derived fused tetracyclic backbone. All of them exhibit good densities, good detonation parameters, and low sensitivity toward mechanical stimuli. Detonation testing revealed that the detonation performance of compound 4c produces a dent of 36 × 31 mm on a lead plate, qualifying it as a potential secondary explosive.

---

High-energy-density materials (HEDMs) are known to store large amounts of chemical energy per unit mass and deliver very high performance upon initiation, which has diverse applications, including weaponry, rocket propulsion, and engineering explosives.^1–4 As carriers of high-density chemical energy, these materials are vital to both national defense technologies and broader industrial and economic development. In the pursuit of high-performance energetic compounds, nitrogen-rich heterocyclic structures have attracted significant attention.^5,6 Current research emphasizes the development of new heterocyclic frameworks that exhibit a positive heat of formation (HOF), high density, favourable oxygen balance, and reduced sensitivity to external stimuli such as impact, friction, and electrostatic discharge.^5,7 Among all heterocyclic ring backbones, 1,2,4-triazole, pyrazole, and pyrimidine have been widely studied due to their good stability, high energy content, and importantly, the ability to incorporate multiple functional groups on them.^8,9 Their energetic performance and oxygen balance can be further optimized by introducing various explosophoric groups such as nitramine (–NHNO₂), trinitromethyl (–C(NO₂)₃), azide (–N₃), and nitroimine (=N–NO₂).^10,11 Polynitro-substituted compounds represent an essential class of high-performing energetic materials.^12,13 In particular, the trinitromethyl and nitramino groups significantly enhance the oxygen balance, nitrogen content, density, and explosive performance of energetic compounds. As highly oxygen-rich and thermally labile fragments, they act as a powerful oxidizer, promoting rapid gas generation and heat release during detonation.¹⁴ When combined in a single molecule, trinitromethyl and nitramine groups act synergistically to enhance detonation velocity and pressure while maintaining acceptable thermal and mechanical stability.¹⁵ The demand for energetic materials that offer high thermal stability, low impact sensitivity, and elevated HOFs continues to rise. In this context, nitrogen-rich energetic salts have become promising HEDMs due to their balanced energetic properties.^16,17 Strategic cation–anion pairing designed for specific performance goals offers a flexible platform for designing new materials.¹⁸ Recently, significant attention has been given to the design of energetic molecules featuring fused heterocycles.^19,20 Compared to single-ring systems, fused molecules offer several advantages, such as rigid frameworks, multiple functionalization sites, extended π-conjugation, and a high proportion of sensitive C–N, N–N, and N–O bonds.²¹ While bicyclic and tricyclic fused systems have been extensively studied, there are few reports on fused tetracyclic backbones, mainly due to synthetic challenges as shown in Fig. 1b.^22–24 Despite these challenges, recent advancements have explored innovative strategies, including treating the explosive molecule itself as a modular scaffold for constructing “hybrid” energetic systems. Borrowing from the concept of “privileged scaffolds” in medicinal chemistry,²⁵ which are chemical frameworks that consistently yield compounds with desirable properties when derivatized, this approach enables the design of hybrid molecules with enhanced energetic characteristics. Fused-ring hybridization paves new ways to develop energetic molecules that combine the strengths of multiple structural motifs.²⁶ Regardless of these difficulties, we successfully designed and synthesized a series of energetic salts based on pyrazolo[3,4-d]pyrimidine-derived fused tetracyclic compounds. All synthesized compounds were thoroughly characterized by infrared (IR) spectroscopy, proton and carbon nuclear magnetic resonance (¹H and ¹³C NMR), elemental analysis, and TGA-DSC. These new compounds demonstrate well-balanced properties such as superior detonation performance, positive HOFs, good thermal stability, and well-controlled impact and friction sensitivities when compared to conventional explosives. Their promising properties establish them as strong candidates for practical applications and contribute significantly to the advancement of safer, more efficient, and environmentally friendly high-energy-density materials.

Fig. 1 (a) Examples of some traditional energetic materials. (b) Previously reported high-performing energetic salts. (c) Our studies, synthesis of fused-tetracyclic energetic salts.

In our efforts to explore insensitive energetic salts, we synthesized a pyrazolo-pyrimidine fused ring through privileged scaffold hybridization, as illustrated in Schemes 1 and 2. Bisdiethyl 2,2′-(10H-pyrazolo[4,3-e]bis([1,2,4]triazolo)[4,3-a:4′,3′-c]pyrimidine-3,7-diyl)diacetate (2) was obtained in a 73% yield by refluxing 4,6-dihydrazinyl-2H-pyrazolo[3,4-d]pyrimidine (1) with ethyl 3-ethoxy-3-iminopropanoate in acetic acid for 12 h. Subsequent nitration of compound 2 using a mixture of 100% HNO₃ and 98% H₂SO₄ for 10 h afforded diethyl 2,2′-(10H-pyrazolo[4,3-e]bis([1,2,4]triazolo)[4,3-a:4′,3′-c]pyrimidine-3,7-diyl)bis(2,2-dinitroacetate) (3) in 90% yield. Compound 3 was then reacted with nitrogen-rich bases such as aqueous ammonia, hydroxylamine hydrate, and hydrazine monohydrate in ethanol at room temperature for 4 h, forming the corresponding ammonium (4a), hydroxylammonium (4b), and hydrazinium (4c) salts in quantitative yields. Furthermore, compound 2 was treated with ethyl bromoacetate at 70 °C for 12 h to get triethyl 2,2′,2″-(10H-pyrazolo[4,3-e]bis([1,2,4]triazolo)[4,3-a:4′,3′-c]pyrimidine-3,7,10-triyl)triacetate (5) in 70% yield.

Scheme 1 Synthesis of energetic salts 4a–4c and neutral compound 7.

Scheme 2 Synthesis of energetic salts 10a–10c from 9.

Hydrolysis of compound 5 with aqueous sodium hydroxide at 70 °C followed by neutralisation with 6N H₂SO₄ yielded the corresponding triacetic acid derivative 2,2′,2″-(10H-pyrazolo[4,3-e]bis([1,2,4]triazolo)[4,3-a:4′,3′-c]pyrimidine-3,7,10-triyl)triacetic acid (6) in 75% yield. Nitration of compound 6 with 100% HNO₃ and 98% H₂SO₄ at 0 °C to room temperature gave 2-(3,7-bis(trinitromethyl)-10H-pyrazolo[4,3-e]bis([1,2,4]triazolo)[4,3-a:4′,3′-c]pyrimidin-10-yl)acetic acid (7) in 88% yield instead of 3,7,10-tris(trinitromethyl)-10H-pyrazolo[4,3-e]bis([1,2,4]triazolo)[4,3-a:4′,3′-c]pyrimidine (7′). Despite exploring various nitration conditions, the fully nitrated compound 7′ could not be obtained, possibly due to decreased electron density, which reduces the reactivity of the reaction sites as illustrated in Scheme 1.

Tricyclic compound 10H-pyrazolo[4,3-e]bis([1,2,4]triazolo)[4,3-a:4′,3′-c]pyrimidine-3,7-diamine (8) was isolated in 83% yield when molecule 1 was treated with CNBr in 1 M HCl at 70 °C for 15 h. A subsequent nitration reaction of compound 8 was performed with 100% HNO₃ at room temperature, which furnished N,N′-(9H-pyrazolo[4,3-e]bis([1,2,4]triazolo)[4,3-a:4′,3′-c]pyrimidine-3,7-diyl)dinitramide (9)²⁷ in 87% yield. Furthermore, compound 9 was treated with nitrogen-rich bases such as aqueous ammonium, hydroxylammonium, and 3,6,7-triamino-7H-[1,2,4]triazolo[4,3-b][1,2,4]triazol-2-ium (TATOT) in ethanol at room temperature for 4 h to obtain the ammonia (10a), hydroxylamine (10b), and TATOT (10c) salts in quantitative yields as shown in Scheme 2.

A suitable single crystal of compound 5 was obtained in dimethyl sulfoxide solution at room temperature. The compound crystallizes in the monoclinic space group P2₁/c with a calculated crystal density of 1.40 g cm⁻³. Structural analysis reveals that all the ring-fused atoms lie in the same plane, whereas the ester substituents adopt out-of-plane orientations, as illustrated in Fig. 2b.

Fig. 2 (a) Molecular structure of compound 5. (b) Planarity of compound 5.

The ¹⁵N NMR spectra of compounds 4a and 10c were recorded in DMSO-d6, and the chemical shift values are given with regard to CH₃NO₂ as an external standard, as depicted in Fig. 3. All peaks are assigned according to nitrogen atom signals reported in the literature.^28–30 A total of eleven and twenty distinct nitrogen signals were identified and assigned in compounds 4a and 10c, respectively. For compound 4a, the –NO₂ signals appear at N9/N10 (δ = −25.73/−25.84 ppm). The triazole ring nitrogens resonate at N3/N4/N5 (δ = −115.17/−63.74/−74.91 ppm) and N6/N7/N8 (δ = −102.00/−56.81/−71.46 ppm), while the pyrazole ring nitrogens are observed at N1/N2 (δ = −221.49/−85.12 ppm). The ammonium nitrogen is detected at N11 (δ = −225.56 ppm). For compound 10c, the –NO₂ signals are found at N10/N12 (δ = −14.55/−15.33 ppm), and the –N=NO₂ nitrogens resonate at N9/N11 (δ = −112.31/−131.10 ppm).

Fig. 3 ¹⁵N {¹H} NMR spectra of compounds 4a and 10c.

The triazole ring nitrogens appear at N3/N4/N5 (δ = −201.95/−86.33/−177.44 ppm) and N6/N7/N8 (δ = −201.90/−79.89/−152.79 ppm). The pyrazole ring nitrogens resonate at N1/N2 (δ = −205.13/−192.90 ppm). The TATOT ring nitrogens are observed at N13/N14/N15/N16/N17 (δ = −228.94/−317.01/−264.54/−287.44/−264.60 ppm), and the TATOT –NH₂ signals appear at N18/N19/N20 (δ = −331.89/−326.97/−329.84 ppm).

The physicochemical and energetic properties of all newly synthesized compounds are summarized in Table 1. Thermal stability was assessed using differential scanning calorimetry under a nitrogen atmosphere with a heating rate of 5 °C min⁻¹. All compounds displayed good thermal stability, with decomposition temperatures ranging from 134 to 253 °C. Hydroxylammonium salt 4b exhibits lower thermal stability (T_d = 134 °C) compared to salts 4a and 4c. This reduced stability can be attributed to the presence of the hydroxylammonium cation (NH₃OH⁺), which contains an internal N–O bond that is inherently weaker and more thermally labile than the N–H bonds present in ammonium and hydrazinium cations. Upon heating, this N–O bond can undergo facile homolytic or heterolytic cleavage, generating reactive species that promote early thermal decomposition. All compounds have high nitrogen content (>41%), which is beneficial for energy release during detonation and leads to lower pollutant emissions upon decomposition. Density is a key factor in determining the performance and effectiveness of energetic materials, and it was measured using a gas pycnometer in a helium atmosphere at room temperature (25 °C). The densities of newly synthesized compounds range from 1.69 to 1.86 g cm⁻³. The solid-state heats of formation (HOFs) were calculated using the Gaussian 09 software suite.³¹ All synthesized compounds showed high positive HOFs, ranging from 397.68 to 1694.61 kJ mol⁻¹, which are significantly higher than those of benchmark explosives such as HNS, RDX, and HMX. Detonation parameters, including detonation pressure (DP) and velocity of detonation (VOD), were calculated using the Explo5 code (version 7.01.01), based on the computed HOFs and measured densities. The DP values vary between 22.39 and 32.19 GPa, whereas the VOD values range from 7846 to 8776 m s⁻¹. Notably, among all, compound 4c exhibited the highest VOD (8776 m s⁻¹), close to that of RDX (8878 m s⁻¹). The VOD and DP values of all other compounds surpass those of TNT (6881 m s⁻¹ and 19.5 GPa) and HNS (7164 m s⁻¹ and 21.65 GPa).³² Impact sensitivity (IS) and friction sensitivity (FS) tests, which are crucial for guiding the safe use and handling of energetic materials, were performed using a BAM fall hammer and friction tester. All compounds exhibited low sensitivity to external mechanical stimuli, with IS values >35 J and FS values >360 N, respectively. Overall, considering their synthetic feasibility, high thermal stability, positive HOFs, and superior detonation performance, these compounds can be a perfect blend for replacing many presently used secondary benchmark explosives in real-time applications. To evaluate energetic performance, a lead-plate test was carried out for compound 4c (Fig. 4a) because of its superior detonation properties. A 5.0 mm-thick lead witness plate was placed in direct contact with the bottom of the detonator cap (Fig. 4b). The detonator assembly was loaded sequentially with 40 mg of the primary explosive ((E)-1,2-bis(3-azido-5-(trifluoromethyl)-4H-1,2,4-triazol-4-yl)diazene)³⁴ as the initiator, 100 mg of RDX as the booster, and 400 mg of compound 4c as the main charge; initiation was achieved with a standard pyrotechnic ignitor. Explosive performance was assessed by measuring the perforation (dent) diameter in the lead plate after detonation. Compound 4c produced a dent of approximately 36 × 31 mm (Fig. 4c), indicating excellent detonation performance and supporting its candidacy as a secondary explosive.

Fig. 4 Detonation tests. (a) Structure of compound 4c. (b) Illustration of the plate-dent test setup. (c) Lead plate that was blasted out of the hole by using compound 4c.

Table 1 Physicochemical properties of energetic salts 4a to 10c

Comp.	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]	N [%]	OB^i [%]
a Onset decomposition temperature (DSC, 5 °C min^−1). b Density measured using a gas pycnometer (25 °C). c Computed HOF values in the condensed phase. d Detonation velocity. e Detonation pressure. f Impact sensitivity. g Friction sensitivity. h Nitrogen percentage. i Oxygen balance (CO). j Ref. 30. k Ref. 32. l Ref. 33.
4a	193	1.72	397.68	7846	24.20	40	>360	44.34	−21.71
4b	134	1.80	483.30	8357	29.78	35	>360	41.35	−13.49
4c	193	1.86	657.50	8776	32.19	40	>360	47.45	−23.71
7	114, 191	1.75	224.8	8085	26.79	30	360	35.25	2.9
9	213	1.83	730.3	8165	27.38	15	>360	52.50	−24.99
10a	227	1.69	525.85	7935	22.39	40	>360	55.36	−36.13
10b	240	1.72	635.26	8193	26.36	40	>360	50.64	−24.85
10c	253	1.80	1694.61	8677	27.70	40	>360	62.41	−43.28
RDX	210	1.80	86.3	8878	34.90	7.5	120	37.84	0
TATB	360	1.94	−139.5	8114	32.40	>40	>360	32.56	−18.59
TNT	295	1.65	−67	6881	19.5	39.2^l	353	18.50	−24.66

---

In this study, we successfully synthesized a novel series of energetic salts containing tetracyclic fused-ring frameworks. The synthesized compounds demonstrate an optimal balance of physicochemical and energetic properties, including good thermal stability (134 to 253 °C) and high densities (1.69 to 1.86 g cm⁻³). Their high positive heats of formation (397.68 to 1694.61 kJ mol⁻¹) and strong detonation characteristics (VOD: 7846 to 8776 m s⁻¹ and DP: 22.39 to 32.19 GPa) outperform those of several traditional explosives such as TNT and HNS. Notably, compound 4c exhibited the highest VOD (8776 m s⁻¹), comparable to that of RDX. Detonation testing revealed that the detonation performance of compound 4c produces a dent of 36 × 31 mm on a lead plate, qualifying it as a potential secondary explosive.

Conflicts of interest

The authors declare no competing financial interest.

Data availability

The data supporting this article have been included as part of the supplementary information (SI). Supplementary information is available. See DOI: https://doi.org/10.1039/d5dt02893k.

CCDC 2482600 contains the supplementary crystallographic data for this paper.³⁵

Acknowledgements

S.N. thanks IIT Kanpur for the fellowship and infrastructure. S.D. is grateful for the financial support from Core Research Grant CRG/2023/000007 from the Science and Engineering Research Board, Department of Science and Technology, Government of India.

References

1. P. F. Pagoria, G. S. Lee, A. R. Mitchell and R. D. Schmidt, Thermochim. Acta, 2002, 384, 187–204.
2. M. Anniyappan, M. B. Talawar, R. K. Sinha and K. P. S. Murthy, Combust., Explos. Shock Waves, 2020, 56, 495–519.
3. J. C. Oxley, Explos. Eff. Appl., 1998, 137–172.
4. T. M. Klapötke, Chemistry of High-Energy Materials, De Gruyter, Berlin, Boston, 6th edn, 2022.
5. J. P. Agrawal and J. E. Field, Prog. Energy Combust. Sci., 1998, 24, 1–30.
6. J. Tang, H. Wei Yang and G. Bin Cheng, Energ. Mater. Front., 2023, 4, 110–122.
7. T. M. Klapötke, Propellants, Explos., Pyrotech., 2023, 48, e202380331.
8. D. Su, L. Yang, J. Cai, Q. Lai, P. Yin and S. Pang, Mater. Chem. Front., 2025, 9, 2551–2558.
9. H. Gao and J. M. Shreeve, Chem. Rev., 2011, 111, 7377–7436.
10. J. Li, Y. Liu, W. Ma, T. Fei, C. He and S. Pang, Nat. Commun., 2022, 13, 5697.
11. A. K. Sikder and N. Sikder, J. Hazard. Mater., 2004, 112, 1–15.
12. Y. Tang, C. He, G. H. Imler, D. A. Parrish and J. M. Shreeve, J. Mater. Chem. A, 2018, 6, 8382–8387.
13. J. Singh, R. J. Staples and J. M. Shreeve, ACS Appl. Mater. Interfaces, 2021, 13, 61357–61364.
14. P. Yin, J. Zhang, C. He, D. A. Parrish and J. M. Shreeve, J. Mater. Chem. A, 2014, 2, 3200–3208.
15. P. Chen, H. Dou, J. Zhang, C. He and S. Pang, ACS Appl. Mater. Interfaces, 2023, 15, 4144–4151.
16. L. Hu, P. Yin, G. Zhao, C. He, G. H. Imler, D. A. Parrish, H. Gao and J. M. Shreeve, J. Am. Chem. Soc., 2018, 140, 15001–15007.
17. P. Yin, C. He and J. M. Shreeve, J. Mater. Chem. A, 2016, 4, 1514–1519.
18. Y. Zhou, H. Gao and J. M. Shreeve, Energ. Mater. Front., 2020, 1, 2–15.
19. M. Deng, Y. Feng, W. Zhang, X. Qi and Q. Zhang, Nat. Commun., 2019, 10, 1339.
20. H. Gao, Q. Zhang and J. M. Shreeve, J. Mater. Chem. A, 2020, 8, 4193–4216.
21. S. Nehe, A. K. Yadav, V. D. Ghule and S. Dharavath, Org. Lett., 2025, 27, 5165–5169.
22. J. Singh, R. J. Staples and J. M. Shreeve, ACS Appl. Mater. Interfaces, 2021, 13, 61357–61364.
23. T. Zhu, C. Li, J. Tang, C. Xiao, L. Chen, G. Cheng and H. Yang, Cryst. Growth Des., 2024, 24, 8847–8854.
24. C. Lei, J. Tang, Q. Zhang, G. Cheng and H. Yang, Org. Lett., 2023, 25, 3487–3491.
25. Shaveta, S. Mishra and P. Singh, Eur. J. Med. Chem., 2016, 124, 500–536.
26. S. Nehe, A. K. Yadav, V. D. Ghule and S. Dharavath, Chem. Commun., 2025, 61, 9047–9050.
27. S. Nehe, V. D. Ghule and S. Dharavath, Org. Lett., 2025, 27, 13810–13815.
28. Y. Tang, C. He, L. A. Mitchell, D. A. Parrish and J. M. Shreeve, J. Mater. Chem. A, 2015, 3, 23143–23148.
29. Z. Xu, G. Cheng, S. Zhu, Q. Lin and H. Yang, J. Mater. Chem. A, 2018, 6, 2239–2248.
30. A. K. Yadav, V. D. Ghule and S. Dharavath, ACS Appl. Mater. Interfaces, 2022, 14, 49898–49908.
31. M. J. Frisch, G. W. Trucks, H. B. Schlegel, G. E. Scuseria, et al., Gaussian 09, revision A.1, Gaussian, Inc., Wallingford, CT, 2009.
32. Z. Xu, G. Cheng, H. Yang, X. Ju, P. Yin, J. Zhang and J. M. Shreeve, Angew. Chem., Int. Ed., 2017, 56(21), 5633–5941.
33. S. Zeman and V. B. Patil, FirePhysChem, 2025, 5, 68–73.
34. A. K. Yadav, S. Kukreja and S. Dharavath, JACS Au, 2025, 5, 1031–1038.
35. CCDC 2482600: Experimental Crystal Structure Determination, 2026,  DOI:10.5517/ccdc.csd.cc2pbbw8.

---