Energetic Materials Based on N-substituted 4(5)-nitro-1,2,3-triazoles

The regularities and synthetic potentialities of the alkylation of 4(5)-nitro-1,2,3-triazole in basic media were explored, and new energetic ionic and nitrotriazole-based coordination compounds were synthesized in this study. The reaction had a general nature and ended with the formation of N1-, N2-, and N3-alkylation products, regardless of the conditions and reagent nature (alkyl- or aryl halides, alkyl nitrates, dialkyl sulfates). This reaction offers broad opportunities for expanding the variability of substituents on the nitrotriazole ring in the series of primary and secondary aliphatic, alicyclic, and aromatic substituents, which is undoubtedly crucial for solving the problems related to both high-energy materials development and medicinal chemistry when searching for new efficient bioactive compounds. An efficient methodology for the separation of regioisomeric N-alkyl(aryl)nitrotriazoles has been devised and relies on the difference in their basicity and reactivity during quaternization and complexation reactions. Based on the inaccessible N3-substitution products that exhibit a combination of properties of practical importance, a series of energy-rich ionic systems and coordination compounds were synthesized that are gaining ever-increasing interest for the chemistry of energy-efficient materials, coordination chemistry, and chemistry of ionic liquids.

The favorable properties of the enhanced biological activities of the triazole ring include hydrogen bonding capability under in vivo conditions, a strong dipole moment, high chemical stability (they are typically inert toward oxidizing and reducing agents), and rigidity [8].
1,2,3-Triazole nitro derivatives-five-membered heteroaromatic systems bearing three endocyclic nitrogen atoms and exocyclic explosophoric NO 2 groups-are commonly used in the development of efficient high-energy compounds, including ionic ones, that exhibit enhanced technological and operational safety for various applications [9][10][11][12][13][14]. The aromatic nature provides the triazole heterocyclic molecule with high thermal and chemical stabilities and a low sensitivity to mechanical stimuli [9,10]. The three coupled nitrogen atoms united into the five-membered heterocyclic system preserve the energy potential of the azido group and impart quite a high enthalpy of formation to 1,2,3triazoles [15]. The functionalization with supplemental energy-rich moieties in the form of NO 2 groups promotes enhanced density and increases the number of oxidizing elements (oxygen balance) required to oxidize components and maximize the energetic potential of the overall system [16]. The capability of accepting various metal ions and oxoacid anions opens the door to the synthesis of various supramolecular ionic systems, including the oxygen-enriched ones in the active form, starting from cations of triazolium heterocycles [10]. Such ionic systems holds promise as energetic compounds, which concurrently combine low sensitivity to mechanical stimuli and high energetic performance [17].
The high potential for practical application of 1,2,3-triazole derivatives provides for the highly relevant problem of finding directed synthesis methods for various functionalized triazoles-bearing systems.
There are two well-known, conceptually distinct approaches for the synthesis of Nsubstituted 4-nitro-1,2,3-triazoles. The first approach refers to the heterocyclization of nitrogen derivatives that contain activated C-C, N-N, and C-N bonds. A good deal of original papers and review articles report the findings of the first approach [18,19]. However, such methods are limited by the synthesis directions of inaccessible N3-substituted nitro derivatives of 1,2,3-triazoles.
The rational method for the functionalization of 1,2,3-triazole nitro derivatives for the potential synthesis of N1, N2, and N3 isomers is by alkylating unsubstituted 4-nitro-1,2,3-triazoles. Varying the nature of substituents and their location within the structure of N-substituted nitrotriazoles imparts a specified set of characteristics to the compounds and allows the control of their biological activity, energy performance, complexing, and other useful properties.
Along with that, inaccessible N3-substitution products in the series of isomeric N-substituted 4-nitro-1,2,3-triazoles are of special interest for the development of highenergy [26,27], ionic [28][29][30], and polymeric materials [31] and metal complexes [32,33]. Due to the low accessibility, N3-substitution products are almost understudied. At the same time, they may serve as promising cages for high-energy materials because they have a unique combination of extreme and practically important properties (high enthalpy of formation [34], basicity [35]). From the synthetic standpoint, N3 derivatives arouse a huge interest, as they are more efficient in quaternization [36] and complexation [32,33] reactions among the isomeric N-substituted 4-nitro-1,2,3-triazoles. Such reactions are a powerful tool to produce the important class of compounds-energy-rich ionic systems and coordination compounds starting from nitrotriazoles.
Thus, the present study was focused on the synthesis and transformations of a wide array of N-alkyl(aryl)-nitrotriazoles differing in substituent types. The present study reports the results of the alkylation of 4-nitro-1,2,3-triazole in alkali whereby the triazole heterocycle is functionalized over all the three endocyclic nitrogen atoms. The unique properties of the N3 isomers allow for new quaternization and complexation processes that afforded a series of ionic and coordination compounds that have a set of characteristics combining enhanced energy performance and safety.

Materials and Methods
All the reagents and solvents were used as received.  [37]. 1 H and 13 C NMR spectra were recorded on a Bruker Avance III spectrometer (Bruker Corporation, Billerica, MA, USA). 1H NMR spectra were acquired at 400.13 MHz, while 13 C NMR spectra were taken at 100.61 MHz. The measurements were conducted at 298 K unless otherwise stated. The spectra were calibrated using residual solvent signals (DMSO-d 6 : 2.50 ppm for 1 H, 39.5 ppm for 13 C). All NMR spectra of the new compounds are shown in the Supplementary Materials (Figures S1-S21). IR spectra (KBr): Simex FT-801 FTIR spectrometer (Simex, Novosibirsk, Russia). The melting point was determined on a Stuart SMP30 apparatus (Bibby Scientific Ltd., Stone, Staffordshire, UK). Elemental analyses were done on a Thermo Scientific Flash EA1112 CHNS elemental analyzer (Thermo Fisher Scientific, Waltham, MA, USA) for carbon, hydrogen, nitrogen, and oxygen contents. The XRD analysis was performed on a Bruker KAPPA APEX II CCD diffractometer (Bruker AXS GmbH, Karlsruhe, Germany) (λ(MoKα) = 0.71073 Å, ϕ,ω-scans of narrow (0.5 • ) frames). The density of the synthesized samples was measured on a AccuPyc II 1340 helium pycnometer (Micromeritics, Norcross, GA, USA) at 25 • C.
The reagents were procured from commercial sources and used as received unless otherwise stated. The commercially available compounds were used without additional purification unless otherwise stated. Triazole 1 was synthesized by the procedure reported [37].
Synthesis of triazoles 2-4a, 2-4b, 2-4c, 2-4d, 2-4e, 2-4f, 2-4g, 2-4h (general procedure). A suspension of triazoles 1 (2.85 g, 25 mmol) in ethanol (15 mL) (or water, 7.5 mL) and the corresponding alkali metal hydroxide (25 mmol) was heated to 40 • C with stirring until a solution was prepared. Then, dialkyl sulfate (benzyl chloride) (22.5 mmol, 0.9 equiv) or alkyl halide (50 mmol) was added and stirred. Low-boiling alkyl halides (EtBr, Pr i Br) were added dropwise with constant stirring. The reaction temperature and time for each case are summarized in Table 1. After the reaction was completed, the reaction mixture in ethanol was cooled to room temperature and concentrated in a rotary evaporator. The residue was treated with CH 2 Cl 2 (3 × 25 mL). The reaction mixture in water was cooled, and extraction with CH 2 Cl 2 (3 × 25 mL) was performed. The combined organic layers were washed successively with 3% aqueous sodium carbonate (7.5 mL), water (7.5 mL), dried over MgSO 4 , and then concentrated in a rotary evaporator. The overall yield and the composition of mixed alkylation products are listed in Table 1. Table 1. Alkylation of 4(5)-nitro-1,2,3-triazole with different alkylating agents. procedure). A suspension of triazoles 1 (2.85 g, 25 mmol) in ethanol (15 mL) (or water, 7.5 mL) and the corresponding alkali metal hydroxide (25 mmol) was heated to 40 °С with stirring until a solution was prepared. Then, dialkyl sulfate (benzyl chloride) (22.5 mmol, 0.9 equiv) or alkyl halide (50 mmol) was added and stirred. Low-boiling alkyl halides (EtBr, Pr i Br) were added dropwise with constant stirring. The reaction temperature and time for each case are summarized in Table 1. After the reaction was completed, the reaction mixture in ethanol was cooled to room temperature and concentrated in a rotary evaporator. The residue was treated with CH2Cl2 (3 × 25 mL). The reaction mixture in water was cooled, and extraction with CH2Cl2 (3 × 25 mL) was performed. The combined organic layers were washed successively with 3% aqueous sodium carbonate (7.5 mL), water (7.5 mL), dried over MgSO4, and then concentrated in a rotary evaporator. The overall yield and the composition of mixed alkylation products are listed in Table 1. Synthesis of triazoles 2−4j. To a suspension of triazoles 1 (2.85 g, 25 mmol) in ethanol (15 mL) was added an equimolar quantity of sodium hydroxide and cyclohexyl nitrate (22.5 mmol) and stirred at 78−80 °С for 13 h. 1 Н NMR spectroscopy identified the formation of three isomeric N-cyclohexylnitrotriazoles 2−4j (conversion degree of the starting cyclohexyl nitrate did not exceed 1%) in the reaction mixture. The reaction mixture was cooled to room temperature and ethanol was removed in vacuo. To the residue was added water (7.5 mL), the whole mixture was heated to 90−95 °С and held Note: a KOH was used as the base, while NaOH was used in all of the other reactions. b Time is expressed in minutes. c Ratios obtained by comparing peak integrations in the 1 H NMR spectrum of the crude reaction product.

Synthesis of triazoles 2-4j.
To a suspension of triazoles 1 (2.85 g, 25 mmol) in ethanol (15 mL) was added an equimolar quantity of sodium hydroxide and cyclohexyl nitrate (22.5 mmol) and stirred at 78-80 • C for 13 h. 1 H NMR spectroscopy identified the formation of three isomeric N-cyclohexylnitrotriazoles 2-4j (conversion degree of the starting cyclohexyl nitrate did not exceed 1%) in the reaction mixture. The reaction mixture was cooled to room temperature and ethanol was removed in vacuo. To the residue was added water (7.5 mL), the whole mixture was heated to 90-95 • C and held for 25 h with stirring. The product was isolated in a manner similar to the previous procedure. The overall yield and the ration of isomers 2-4j are specified in Table 1.
Salts 5e,f,h were isolated as follows: after being diluted, the reaction mixture was extracted with CH 2 Cl 2 (20 mL) to recover products 5e,f,h together with unreacted triazoles 2e,f,h and 3e,f,h. The organic layer was concentrated in a rotary evaporator and the residue was treated with Et 2 O. The precipitated products were combined by filtration and washed with Et 2 O to furnish salts 5e,f,h.
Salts 5e,f,h were isolated as follows: after being diluted, the reaction mixture was extracted with CH2Cl2 (20 mL) to recover products 5e,f,h together with unreacted triazoles 2e,f,h and 3e,f,h. The organic layer was concentrated in a rotary evaporator and the residue was treated with Et2O. The precipitated products were combined by filtration and washed with Et2O to furnish salts 5e,f,h.
Salts 5a−d and 5j were compatible by the spectral characteristics with the compounds synthesized and characterized previously [36].   for 25 h with stirring. The product was isolated in a manner similar to the previous procedure. The overall yield and the ration of isomers 2−4j are specified in Table 1.
Salts 5e,f,h were isolated as follows: after being diluted, the reaction mixture was extracted with CH2Cl2 (20 mL) to recover products 5e,f,h together with unreacted triazoles 2e,f,h and 3e,f,h. The organic layer was concentrated in a rotary evaporator and the residue was treated with Et2O. The precipitated products were combined by filtration and washed with Et2O to furnish salts 5e,f,h.

X-Ray Crystallography
Single crystal X-ray diffraction intensity data were collected at 296(2) K using a Bruker APEX-II CCD diffractometer equipped with graphite monochromated MoKα radiation (λ = 0.71073 Å). Data reduction was carried out using the program Bruker SAINT, and an empirical absorption correction was applied with the Bruker SADABS
Single crystal X-ray diffraction intensity data were collected at 296(2) K using a Bruker APEX-II CCD diffractometer equipped with graphite monochromated MoKα radiation (λ = 0.71073 Å). Data reduction was carried out using the program Bruker SAINT, and an empirical absorption correction was applied with the Bruker SADABS program based on the multi-scan method. The structure of the complex was solved by the direct method (SHELXT-18) and refined by the full-matrix least-square technique (SHELXL-18) with anisotropic thermal parameters. All hydrogen atoms were refined isotropically in riding positions. CCDC 2119451 contains the supplementary crystallographic data of 6. These data can be obtained free of charge from the Cambridge Crystallographic Data Centre.
More information can be found in the Supplementary Materials (Tables S1 and S2).

Results and Discussion
The first phase of this study was to explore the alkylation regularities of triazole 1 in basic media. All the three available reaction sites-N1, N2, and N3 heteroatoms-were found to undergo an electrophilic attack, irrespective of the alkylating agent nature (alkylor aryl halides, alkyl nitrates, dialkyl sulfates), solvent and base types, and reaction temperature and time. All the cases resulted in high yields of three regioisomeric N-alkylation products 2-4 among which N2-substituted derivatives 3 were mostly prevailing (Table 1).
At the first stage, the equimolar quantity of alkali produced easily a highly nucleophilic anion from NH-triazole 1 that had quite a high acidity (pKa 4.8). The latter underwent an attack by different electrophilic agents to furnish N-substitution products.
The structure of the alkylating reagent determined significantly the reaction conditions and the ratio of alkylation products. The reaction with dialkyl sulfates (DAS) at 78 • C in ethanol or at 84-90 • C in water in excess of triazoles 1 was completed within 5-10 min (Entries 1-4). Prolongation of the reaction involving N-substituted azoles, including Nalkyl-4-nitro-1,2,3-triazoles [20,38], in acidic media or by using activated alkylating reagents may be accompanied by the migration of substituents and interconversion of regioisomers. An increase in time of the reaction between triazole 1 and diethyl sulfate from 5 min to 10-15 h did not considerably alter the composition and ratio of isomers 2-4b (Entries 4-6).
To exclude possible quaternization processes when triazole 1 is reacted with DAS, the alkylating reagent was used in deficiency (0.9 equiv). Since alkyl halides do not engage in the quaternization reaction with N-substituted 4-nitro-1,2,3-triazole, excess alkyl halides (2-3 equiv) were utilized in the alkylation of triazole 1, which is especially important when using lower alkyl halides because of possible reaction losses associated with their low boiling points. When alkyl halides or DAS were employed in ethanol, isomer 3 was prevailing in mixed alkylation products 2-4 in all cases. The proportion of 3 in the mixture was 53-57% (Entries 1, 3, 4, 7-13). The alkylation conditions using water as the polar solvent increased naturally a proportion of the most polar N1-isomer 2, in which case one of regioisomers 2 or 3 (Entries 2, 4-6, 9) was observed to dominate slightly (Entries 2, [4][5][6]9).
The content of minor N3-isomer 4 in the mixed alkylation products of triazole 1 and dialkyl sulfates was 11-12% (Entries 1-4) and did not exceed 9% when alkyl halides were used (Entries 7-16). A minimum proportion of isomer 4 (as little as 2%, Entry 15) was documented in the reaction with ethylhexyl nitrate, which is likely due to the steric effects of the ethylhexyl substituent. Unexpectedly, when cyclohexyl nitrate was used, the composition of the isomers changed dramatically, and the proportion of 4 came up to 18% (Entry 16). Moreover, the alkylation reaction between triazoles 1 and cyclohexyl nitrate in basic media considerably diminished the yield of products 2-4j. The yield of the target N-cyclohexylnitrotriazoles 2-4j in water was not above 8%, and when reacted in alcohol, the products were documented only in the 1 H NMR spectra. This is attributed to the tendency of cyclohexyl nitrate to undergo a side elimination reaction to form cyclohexene. The latter did not probably participate in the primary reaction; instead, it was consumed during polymerization. As opposed to the conditions considered, unsaturated alicycles have successfully been used to alkylate azoles in acidic media [41,42].
Benzyl chloride used as the activated electrophilic reagent afforded mixed regioisomers containing chiefly N1-substitution product 2h. The proportion of 2h in the mixture reached 64% (Entry 14).
Nitrotriazolium salts 5a-d, 5g, 5j (where R = Me, Et, Pr, i-Pr, Bn, cyclohexyl) precipitated as crystals from the reaction mixture. As the length of the substituent (R = Bu, i-amyl, 2-ethylhexyl) increased due to the higher solubility, salts 5e,f,h required other isolation conditions: products 5e, f, and h were extracted with dichloromethane from the water-diluted reaction mixture; the solvent was removed in vacuo; they were treated with diethyl ether, and the precipitated products were combined by filtration to yield salts 5e,f,h individually.
Treatment of mixed N-alkyl nitrotriazoles 2-4c with copper(II) chloride afforded coordination compound 6 in which N3-isomer 4c acted as the monodentant ligand (L) due to the N1 atom being involved in the coordination (Scheme 2). The selective formation of complex isomer 4c was also due to the higher basicity of the N3 derivatives from among their regioisomers 2-4c [35]. The resultant complex 6 was easily decomposed by water to form free ligand 4c. Scheme 2. Complexation of triazole 4c.
Thus, the difference in basicity [35] and reactivity during the quaternization [36] and complexation [32,33] processes typical of isomeric alkyl nitrotriazoles was used herein to isolate inaccessible N3-substituted derivatives from the resultant mixed regioisomers 2a-j, 3a-j and 4a-j and use them for the synthesis of high-energy ionic materials and coordination compounds.

Conclusions
Synthetic methods for a wide array of N-alkyl(aryl)-4(5)-nitro-1,2,3-triazoles (alkyl = Me, Et, Pr, Pr i , Bu, 2-ethylhexyl, cyclohexyl; aryl = Bn), including inaccessible N3-substitution products, have been devised herein. Due to the unique physicochemical characteristics (the highest enthalpies of formation, density, basicity), the inaccessible N3-substitutuion products appeared to be quite attractive as cages for the construction of energetic ionic and coordination compounds. The synthesis involved the N-monoalkylation in basic media, quaternization using the highly efficient t-BuOH-HClO 4 system, and complexation with transition metal salts. The methodology for the separation of regioisomeric N-alkyl(aryl)nitrotriazoles by quaternization and complexation reactions warranted the synthesis of a range of new energyefficient nitrotriazole salts and coordination compounds.