Novel Carbon-Carbon Bond Oxidative Cleavage of Hexabenzylhexaazaisowurtzitane by n-BuONO and (NH₄)₂Ce(NO₃)₆

Abstract

Treatment of 2,4,6,8,10,12-hexabenzyl-2,4,6,8,10,12-hexaazatetracyclo-[5.5.0.0^5,9.0^3,11]dodecane (1) with n-butyl nitrite or ammonium cerium nitrate results in novel C(1)-C(7) oxidative cleavage to give 1,3,4,5,7,8-hexabenzyl-cis-cisoid-cis-hexahydro-1H,5H-diimidazolinium[4,5-b:4′,5′-e]pyrazine dinitrate (2).

Introduction

2,4,6,8,10,12-Hexabenzyl-2,4,6,8,10,12-hexaazatetracyclo[5.5.0.0^5,9.0^3,11]dodecane (hexabenzyl-hexaazaisowurtzitane, 1) is an interesting polyaza “cage” compound synthesized recently [1]. In an effort to study the chemical behaviour of 1, we have explored a series of debenzylation method to remove the N-benzyl groups in 1 [2]. Reductive acetyldebenzylation of 1 (H₂, 20%Pd(OH)₂/C, Ac₂O) gives 2,6,8,12-tetraacetyl-4,10-dibenzyl-2,4,6,8,10,12-hexaazatetracyclo[5.5.0.0^5,9.0^3,11]dodecane[2,3], which could be further transformed to hexanitrohexaazaisowurtzitane [2]. In this communication we wish to report an unexpected carbon-carbon oxidative cleavage of 1 caused by n-BuONO and (NH₄)₂Ce(NO₃)₆, respectively (Scheme 1).

Results and Discussion

n-BuONO is a convenient reagent for N-dealkylnitrosation of N,N-dialkyl aromatic amines with preferential debenzylation [4]. However, under the same condition, compound 1 did not go through N-dealkylnitrosation. Instead, diimidazolinium dinitrate 2 was obtained in 42% yield, whose structure was established through the analyses of IR, ¹H and ¹³C NMR, MS and elemental microanalysis. In particular, the IR spectrum shows a strong peak at 1640 cm⁻¹, indicating the existence of iminium cation, which was further confirmed by ¹H NMR spectrum (δ 9.04 ppm, 2H) and ¹³C NMR spectrum (δ 158.4 ppm, d), and a very intense band of nitrate anion at 1382 cm⁻¹. The elemental analysis and the field desorption mass spectrum (m/z 770, M–NO₃⁻, 100%), is consistent with formula C₄₈H₄₈N₈O₆ . In addition, the ¹H and ¹³C NMR spectra also indicated that the molecule was mirror symmetric. These results demonstrate that the product 2 is 1,3,4,5,7,8-hexabenzyl-cis-cisoid-cis-hexahydro-1H,5H-diimidazolinium[4,5-b:4′,5′-e]pyrazine.

Under mild conditions, (NH₄)₂Ce(NO₃)₆ can remove the N-(4-methoxybenzyl) group on 2,5-piperazinediones [5]. However, when 1 was exposed to (NH₄)₂Ce(NO₃)₆, instead of debenzylation, 2 was isolated in 59% yield.

The easy cleavage of C(1)-C(7) bond reflects that the cage skeleton of 1 is somewhat strained. Crystal structure analysis of hexa(4′-chlorobenzyl)hexaazaisowurtzitane shows that the framework C-C bonds are longer than usual value for unstrained C_sp3-C_sp3 bond and C(1)-C(7) bond [1.579(3)Å] is the longest [1b]. This implys that C(1)-C(7) bond is probably the weakest C-C bond in this cage skeleton.

A mechanism that accounts for the observed oxidative cleavage of 1 to 2 is depicted in Scheme 2. The initially formed aminium radical cation 3 rapidly undergoes C(1)-C(7) cleavage followed by a second electron loss to give diimidazolinium dinitrate 2. It has been reported that 1,2-diamine radical cations undergo rapid C-C bond fragmentation to form an α-amino radical and an iminium ion [6], and iminium salts are generally believed to be the key intermediates during the oxidation of tertiary amines [7]. The readily oxidative cleavage of 1 must arise from the through-bond interaction between N(2), N(6), N(8) and N(12) atoms, which stabilizes the intermediate-like transition state relative to the ground state. Relief of strain energy contained within the hexaazaisowurtzitane framework and formation of the resonance-stabilized imidazolinium ion provides the driving force for the oxidative cleavage of C(1)-C(7) bond. The similar type of Grob fragmentation was also observed in the reaction of triethylenediamine with either ClO₂ or HOCl [8].

In oxidative dealkylation of tertiary amine, the intermediate iminium cation, which are generally believed to be the key intermediates, is hydrolyzed more or less rapidly, in aqueous solution, with the formation of the corresponding secondary amine [7]. Usually, imidazolinium salts are also too labile to resist hydrolysis [9]. The high stability of 2 towards hydrolysis may be partially attributed to being capped of the cage skeleton by the six sterically hindered and hydrophobic benzyl groups.

Experimental

Oxidation of Hexaazahexbenzylisowurtzitane (1) with n-BuONO

A mixture of 1 (501 mg, 0.707 mmol), n-BuONO (5.0 mL, 55 mmol), NH₄Cl (50 mg, 0.99 mmol) and H₂O (150 μL, 8.3 mmol) was refluxed under N₂ for 1h. Volatile material was then evaporated in vacua and the residue was washed with a small amount of water. Recrystallization of the crude solid from CH₃CN/CHCl₃/hexane afforded pure 2 as colorless crystals (249 mg, 42.3%), mp 224.2~225.0 °C; IR (KBr, cm⁻¹): 1640(C=N⁺), 1382(NO₃⁻;), 692; ¹H NMR (DMSO-d₆ ,60MHz): δ 3.93(s, 4H, CH₂), 4.59(d, 4H, J_AB=15.0Hz, CH₂), 4.99(d, 4H, J_AB=15.0Hz, CH₂), 5.33(s, 4H, CH), 6.9~7.6 (m, 30H, Ph), 9.04(s, 2H, HC=N⁺) ; ¹³C NMR (DMSO-d₆, 75Hz): δ 48.2(t), 58.4(t), 68.9(d), 127.9(d), 128.0(d), 128.3(d), 128.5(d), 128.7(d), 129.0(d), 133.4(s), 135.9(s), 158.4(d); MS (FD, m/z): 770(M⁺–NO₃, 100%). Anal. Calcd. for C₄₈H₄₈N₈O₆: C, 69.21; H, 5.81; N, 13.45; O, 11.52; Found: C, 69.13; H, 6.00; N, 13.67; O, 11.37.

Oxidation of Hexaazahexbenzylisowurtzitane (1) with (NH₄)₂Ce(NO₃)₆

A solution of 1 (710 mg, 1.00 mmol) and (NH₄)₂Ce(NO₃)₆ (12.995 g, 23.70 mmol) in acetonitrile (75 mL) and water (25 mL) was stirred at r.t. for 24h. EtOAc (50 mL) was then added. The organic layer was separated, washed with water, dried over MgSO₄ and evaporated in vacua. The residual solid was recrystallized from CH₃CN/CHCl₃/ hexane to give pure 2 as colorless crystals (490 mg, 58.8%).