Synthesis of 2,4,6,8,10-pentaaza[3.3.3]propellane substituted with different groups

Polyaza[3.3.3]propellanes have good symmetry and strong ring tension, which are suitable as the skeleton structure of functional materials such as high energy density materials. Based on the single benzyl derivative of 3,7,9.11-tetraoxo-2,4,6,8,10-pentaaza[3.3.3]propellane (compound3), a series of 2,4,6,8,10- pentaaza[3.3.3]propellane derivatives, such as4a-cand their reduced derivatives5a-c, were synthesized successfully.


Introduction
Tricyclic propellanes are a kind of polycyclic compounds in which three ring systems share a single bond ( Figure 1) [1][2][3][4][5]. They have high reactivity and exist in many natural products [6][7][8][9][10][11][12][13]. Since the propellanes were firstly reported by Ginsburg [14] in 1965, they have aroused the interest of many chemists [15][16][17]. Nitrocyclopropellanes, a class of heterocyclic propellanes, can be easily transformed to N-substituted compounds due to the high reactivity of nitrogen atoms, and they have attracted the attention of many researchers [18][19][20]. Because aza [3.3.3]propellanes have good symmetry and compact skeleton, they have good compactness. In 1966, Altman [2] et al first synthesized monoaza [3.3.3]propellane and diaza [3.3.3] propellane, which enabled researchers to started the design and synthesis of azapropellanes. Combined with the influence of space tension on enthalpy of formation, detonation rate and work ability, they are ideal structures of energycontain-ing compounds. The secondary amine in the azapropellanes structure provides an active reaction site for the further introduction of energetic groups, and further reactions to obtain nitrogensubstituted compounds [21].

Results and discussion
Compound 1 was prepared by bromination and urea condensation with diethyl tartrate as raw material according to the literature 22, but it was worth mentioning that the yield of compound 1 increased by 30% here. Compound 1 is difficult to dissolve in most organic solvents, however, when the amount of benzylamine used as a solvent and reactant was increased, compound 1 was successfully transformed to compound 2 in high yield.

Synthesis of glycoluric diethyl ester (1)
Diethyl tartrate (50 mmol, 10.30 g) and NBS (125 mmol, 22.25 g) were added to a 250 mL round bottom flask, then 80 mL 1,2-dichloroethane was added as a solvent, stirred and refluxed under argon. After 4 hours, the solution was cooled to room temperature, adding anhydrous sodium sulfite to the solution. The mixture was distilled to remove the solvent under reduced pressure, adding 40 mL ethyl acetate to dilute the mixture. The solid was filtered out, and brown organic phase was removed in vacuum distillation to give a white oily liquid. A solution of this oily liquid, trifluoroacetic acid (218 mmol, 16.5 mL) and urea (100 mmol, 6.00 g) in 80 mL toluene, were refluxed under argon atmosphere. After 6 hours, the solvent was removed in vacuum distillation and the concentrated solution was stirred for 3 hours in 100 mL ethanol. The mixture was filtered to give a white powder solid 1 (85%

N, N'-Dibenzyl glycolide diamide (2)
Glycoluric diethyl ester 1 (20 mmol, 5.72 g) was added in a round bottom flask containing 60 mL benzylamine, and the mixture was refluxed under argon atmosphere. When the reaction was completed, 100 mL ethanol was added to the resulting mixture. The mixture was stirred at room temperature for 30 minutes to obtain compound 2.

.3] propellane (3)
A mixture of compound 2 (10 mmol, 4.08 g), p-TsOH (30 mmol, 5.17 g) and 60 mL 1,2-dichloroethane was refluxed under argon atmosphere. When the reaction was completed, the solvent was removed under reduced pressure. The residue was stirred in 100 mL ethanol for 3 hours. The white solid was collected by filtration and washed three times with ethanol. The solid was dried under vacuum to obtain compound 3 (97%

3,7,9,11-Tetraoxo-2,4,6,8,10-pentabenzyl-2,4,6,8,10-penta-aza[3.3.3]propellane (4a)
Compound 3 (10 mmol, 3.01 g) and BnBr (60 mmol, 10.26 g) were dissolved in a mixture of solvents (VDMSO : VDMF = 1 : 4) under argon atmosphere. The reaction temperature was cooled using an ice bath. After 5 minutes, NaH (50 mmol, 2.00 g) was added and the resulting mixture was stirred for 1 h. Then the reaction temperature was raised to room temperature and the reaction was continued for another 12 h. When the end of the reaction was detected, reaction mixture was cooled again and diluted with diethyl ether (30 mL). A solution of aq HCl was slowly added to the mixture to quench the unreacted hydride. The resulting mixture was added H2O and extracted with ethyl acetate. The combined organic layers were dried with MgSO4, filtered, and concentrated under reduced pressure. The residue oil was purified by silica gel column chromatography, to provide the compound 4a as a white solid (81%

2,4,6,8,10-Pentabenzyl-2,4,6,8,10pentaaza[3.3.3]propellane (5a)
Compound 4a was dissolved in 50 mL THF, cooling the solution to 0 ℃ with an ice bath. After 5 minutes, LAH (60 mmol, 2.28 g) was added slowly at low temperatures, under refluxing for 12 h. When the reaction was completed, the reaction mixture was cooled to 0 ℃ again. Ethyl acetate (6 mL) was slowly added to the reaction mixture and the resulting mixture was stirred for 30 minutes to quench the residual hydride. A solution of aq NaOH (10%, 12 mL) was added until the sludgy phase disappeared. After stirring for another 20 minutes, the mixture was filtered with EtOAc and the filtrate was evaporated. The yellow oil was purified by silica gel column chromatography to give white solid compound 5a (2.57g, 85%