Rearrangements of N-tert-butylimines under Flash Vacuum Thermolysis conditions

Abstract

In the thesis presented below, results of the research of thermal reaction under gas phase (FVT – flash vacuum thermolysis) tert-butylimines has been described. The starting imines was synthesized by the reaction of corresponding aldehydes with tert-butylamine. The aldehydes was commercially available compounds or was synthesized based on the literature or oryginal procedures. In the next step, obtained N-tert-butylimines 1a-k was reacted under FVT conditions. It has been shown that: N-tert-butyl-(E)-crotonaldimine – (1a) Thermolysed at 800 oC under 3x10-4 hPa led to the mixture of pirol (2) and crotononitrile (3) in a ratio of 3.5:1 and in 85% of total yield. In the same condition 1,4-di-(tert-butyl)-1,4-diazabuta-1,3-diene (1b) led to the 2-methylimidazole (6) in 67% yield. The radical mechanism was proposed for this reaction. The first one (for 1a) assumed the C-N bond cleavage in the first step and then, cyclisation to the pirol 2 or elimination of hydrogen atom to formation of nitrile 3. The second mechanism supposed sequential elimination two methyl radical from tert-butyl group to give imidazole 6. N-benzylidene-tert-butylamine (1c) under FVT conditions at 800 oC under 3x10-4 hPa provided the mixture of 1,2-dimethylindole (8; 55%), 3-methylisoquinoline (9; 24%) and benzonitrile (10; 17%). The proposed mechanism assumed in the first step elimination of the methyl radical from tert-butyl group. The formed isopropyl radical undergo rearrangement to the azirydynyl radical and then cyclization to the indole. The consequence of this mechanism is the change of the atoms sequence of substrate (C-N-C) and product (C-C-N). This reaction pathway does not have any precedent in the literature. N-(tert-butylo)-N-(pirydylo-2-methylidene)amine (1d) under conditions as presented above led to the 3-methylimidazo[1,5-a]pyridine (13) as a major product in 80% yield. The proposed mechanism assumed the elimination of the methyl radical from the tert-butyl group in the first step and then cyclization of the formed isopropyl radical on the pyridyl nitrogen atom. Elimination of the second methyl radical underwent to the major product 13. FVT of N-(tert-butylo)-N-(pirydylo-4-methylidene)amine (1e). In this reaction, carried out at 800 oC under 3x10-4 hPa, the 1,2-dimethylpyrrolo[2,3-c]pyridine (17; 34%), 3-methyl-[2,7]naphthyridine (18; 11%), 3-methyl-[2,6]naphthyridine (19; 10%) and 4-pyridinecarbonitrile (20; 33%) was formed. More complicated reaction mixtures was formed from less symmetric N-(tert-butylo)-N-(pirydylo-3-methylidene)amine (1f). This reaction led to the 1,2-dimethyl-1H-pyrrolo[2,3-b]pyridine (23) as a major product. Furthermore, the 1,2-dimethyl-1H-pyrrolo[3,2-c]pyridine (24), and five methylnaphthyridines (18, 19, and 25-27) and 3-pyridinecarbonitrile (28) was obtained. All of these compounds was separated, purified and was fully characterized and identified. The one general mechanism to explain the formation of all products was proposed. In the first step the elimination of the methyl radical from the tert-butyl group with formation of the isopropyl radical take place. This is the key reaction in the cycle of the transformations. The fact that the reaction of the tert-butylimine contain the imine group next to the C=N double bond led to the imidazole derivatives enable the synthesis in excellent or good yield the 3-methylimidazo[1,5-a]pyrimidine (31), 3-methylimidazo[1,5-a]pyrazine (32), 1-methylimidazo[1,5-a]quinoline (33), 3-methylimidazo[1,5-a]quinoxaline (38) and 3-methylimidazo[5,1-a]isoquinoline (41). The general mechanism for the formation of all products was proposed. All of the reaction described above was also monitored directly by linear coupled FVT apparatus with UV photoelectron spectrometry (PES) in the group of Prof. Anna Chrostowska. All reaction mechanisms and pathways was theoretically calculated also in group of Prof. Anna Chrostowska.