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9.8.1 Product Subclass 1: Azetes

DOI: 10.1055/sos-SD-009-00155

Regitz, M.; Bergsträßer, U.Science of Synthesis, (20019135.

A comprehensive review on this compound class can be found in HoubenWeyl, Vol. E16c, pp 936940. Further reviews are concerned mainly with the synthesis and reactivity of azetes and cover the literature up to 1995.[‌1‌‌3‌]

Theoretical calculations of the resonance energy for the unknown parent azete (azacyclobutadiene) result in a value of 15.5 kcal·mol1 and thus demonstrate the antiaromatic nature of this class of compounds.[‌4‌] Comparison of this value with that of cyclobutadiene (18.0 kcal·mol1)[‌5‌] shows that incorporation of the heteroatom gives some stabilization. Since the isolation of kinetically or \(pushpull\) stabilized cyclobutadiene is possible,[‌6‌] there are no reasons why kinetically or electronically stabilized azetes should not exist.

The first \(pushpull\) stabilized, monocyclic azete was generated by flash vacuum pyrolysis of 4,5,6-tris(dimethylamino)-1,2,3-triazine; the 2,3,4-tris(dimethylamino)azete was frozen out as the red coating on a cold finger (196°C) and characterized by low temperature spectroscopy. The content of the azete was estimated to be about 30% by 1HNMR spectroscopy. Larger amounts of unreacted triazine (>40%) and dimethylcyanamide prevented isolation of the pure compound. Chemical characterization of the azete by trapping reactions was also not possible.[‌7‌] However, the electronic spectral data calculated using the CNDOCI procedure were compatible with the experimentally determined values and thus support the proposed structure.[‌8‌] A thermodynamically stabilized azete was obtained and its existence shown by benzo-condensation: it was generated by the flash-vacuum pyrolysis of 4-phenyl-1,2,3-benzotriazine and characterized by trapping reactions with various 1,3-dienes. The pyrolysate was frozen out on a cold finger at 78°C and then allowed to react with the trapping reagents. In the absence of a trapping reagent warming to room temperature resulted in dimerization with formation of the (also red) 2-phenylbenzazete; isolation was not possible because the pyrolysate contained the benzazete (ca. 51%) as a mixture with the starting material, benzonitrile, 9-phenylacridine, and biphenylene. However, the products isolated from the trapping reactions unequivocally confirmed the existence of a benzazete.[‌9‌,‌10‌] The unsubstituted benzazete can be generated by vacuum pyrolysis (using a CW CO2 laser) of 1,2,3-benzotriazine in the gas phase and characterized by photoelectron spectroscopy.[‌11‌] Theoretical studies have shown that the presence of donor substituents in positions 2 and 4 and acceptor substituents in position 3 has a pronounced stabilizing effect on the azete.[‌12‌] 2,3,4-Trifluoroazete has been generated photochemically in a matrix (77 K) from 4,5,6-trifluoro-1,2,3-triazine and the product identified by mass and IR spectrometry.[‌13‌] Perfluoroalkyl-substituted triazines also give the corresponding azetes on photolysis; however, the products subsequently dimerize or must be trapped by reaction with a 1,3-diene.[‌14‌]

The isolation on a preparative scale of an azete stable at room temperature has been realized: the compound, 2,3,4-tri-tert-butylazete, is prepared by thermolysis of 3-azido-1,2,3-tri-tert-butylcyclopropene (Section[‌15‌] A further approach to 2,3,4-tri-tert-butylazete from 3,4,5,6-tetra-tert-butyl-1,2-diazabicyclo[2.2.0]hexa-2,5-diene (tetra-tert-butyl-Dewar-pyridazine) by thermolysis or irradiation in an argon matrix gives the azete together with 2,2-dimethylpropanenitrile.[‌16‌] 2,3-Di-tert-butyl-4-isopropylazete and 2,4-di-tert-butyl-3-isopropylazete are accessible by analogous routes.[‌17‌] Further attempts to generate azetes by irradiation, thermolysis, or flash-vacuum pyrolysis in a matrix or in the gas phase have been described but result only in the formation of the corresponding alkyne and nitrile fragments and consequently they will not be discussed here (for a comprehensive summary, see the literature[‌2‌,‌3‌]).

Crystal structure analysis of 2,4-di-tert-butyl-3-mesitylazete confirms the planar, slightly distorted rectangular structure of the four-membered ring with alternating bond lengths (CC 159 and 135pm, and CN 158 and 128pm). In contrast, the structural characterization of a (η4-tri-tert-butylazete)cobalt complex reveals almost identical bond lengths in the planar four-membered ring (CC 147.8 and 146.2pm, and CN 143.3 and 142.4pm).[‌18‌] These observations can be explained in terms of delocalization of the π-electrons and reduction of the electron density in the complexed heterocyclic ring in comparison with the free azete. This interpretation is supported by the results of INDO calculations and also by photoelectron spectra.[‌18‌]

The valence tautomerism of 2,3,4-tri-tert-butylazete (1A1B, R1=R2=R3=t-Bu) (Scheme 1) is demonstrated by variable temperature 13CNMR spectroscopy. Thus, at room temperature, which is near the coalescence temperature, a sharp signal at δ 134 for C3 and a broad signal at δ 181 for C2/C4 are observed; the latter becomes sharper at increasing temperatures and splits into two signals at 110°C with δ 158 and 203.[‌15‌] 4-(1-Adamantyl)-2,3-di-tert-butylazete (1, R1=1-adamantyl; R2=R3=t-Bu) behaves analogously,[‌18‌] while the mesityl derivative 1 (R1=Mes; R2=R3=t-Bu) exists exclusively in the form of the valence isomer 1B and its 13CNMR spectrum does not exhibit temperature-dependent changes.[‌19‌]

Scheme 1 Valence Tautomerism of Azetes[‌15‌,‌19‌]

Ab initio calculations on the geometry and IR vibration frequencies of the parent azete confirm the rectangular ground state.[‌20‌‌22‌] The protonation reaction has also been studied using PM3 methods.[‌23‌]

Despite steric shielding, the kinetically stabilized 2,3,4-tri-tert-butylazete is an extremely reactive compound: it exhibits enormous cycloaddition potential and thus provides access to diverse heterocyclic systems. Only a few selected examples are described here to illustrate the breadth of its reactivity; detailed reviews on the reactivity of azetes have been published.[‌1‌‌3‌] 2,3,4-Tri-tert-butylazete is extremely sensitive to oxidation and hydrolysis and must, therefore, always be handled under an inert gas atmosphere. Protic nucleophiles (alcohols, carboxylic acids, and mineral acids) undergo 1,4(2)-addition reactions with the azete to furnish the 1,2-dihydroazetes,[‌24‌] while reaction with water results in ring opening to afford the β-imino ketone.[‌25‌] Triplet oxygen undergoes addition to the C=C bond at 78°C with formation of a thermally labile, bicyclic dioxetane.[‌25‌] Carbon monoxide and the isoelectronic nitriles participate in a [4(2)+1] cycloaddition with the azete to form primary adducts that undergo electrocyclic ring opening to give 2H-pyrrol-2-ones and 3H-pyrrol-3-imines or 2H-pyrrol-2-imines, respectively.[‌25‌] Electron-poor alkynes and phosphaalkynes react regiospecifically with 2,3,4-tri-tert-butylazete by [4(2)+2] cycloaddition to give 1-Dewar-pyridines and 1,3-azaphospha-Dewar-benzenes, respectively.[‌25‌,‌26‌] Photochemical isomerization of these products provides access to the corresponding azaprismanes and azaphosphaprismanes.[‌2‌,‌26‌,‌27‌] Reactions with 1,3-dipoles, such as diazo compounds,[‌25‌] azides,[‌28‌,‌29‌] sydnones, and münchnones, have been reported.[‌30‌] Aldehydes, ketones, and thiocarbonyl compounds also react at room temperature with 2,3,4-tri-tert-butylazete to yield 3-oxa-1-azabicyclo[2.2.0]hexenes and 3-oxa-1-azatricyclo[,6]hexanes and their respective sulfur analogues.[‌31‌] The reaction of 2,3,4-tri-tert-butylazete with in situ generated dichlorocarbene (to give 2H-pyrrole), vinylcarbenes (to give 1-azabicyclo[3.2.0]heptadienes), and (aminophosphinidene)(pentacarbonyl)tungsten complexes (to give 1,2-azaphospholes) have been investigated.[‌32‌]