Studies On The Catalytic Synthesis And The Structure Of 1, 6-dihydro-1,2,4,5-tetrazines And Their Derivatives

Tetrazine is a class of nitrogen-rich element of heterocyclic compounds,which are used for pharmaceuticals,pesticides,explosives,LCD and so on.Therefore,it is very significant to study on the synthesis,structure and property of tetrazine compounds.In this dissertation,we are focused on the synthesis,structure and property of some 3,6-unsymmetrical substituted-1,6-dihydro-1,2,4,5-tetrazines and their derivatives,giving the following findings:1.Studying on the new synthesis method of 3,6-umsymmetrical substituted -1,2,4,5-terazines,and finding that aryl nitrile and substituted benzylcyanide were reacted with 85%hydrazine hydrate in the presence of sulfur to obtain the 3-aryl-6-substituted benzyl-1,2,4,5-tetrazines,the yields were in 19%～39%,which were 4 to 8 times higher than that of the literature.The crystal structures of these compounds showed that the substituents have regular influence on their crystal system and space group.2.It is observed that 1,2,4,5-tetrazines could be reduced to 1,6-dihydro-1,2,4,5-tetrazines in the presence of sodium borohydride with the yields in 11%～18%;if both of 3 and 6 positions of the tetrazine ring were aryls,it would be reduced to 1,2-dibenzylidene hydrazine derivatives rather than corresponding 1,6-dihydro-1,2,4,5 tetrazines.By X-ray crystallographic analysis,3-aryl-6-methyl-1,6-dihydro-1,2,4,5-tetrazines can be considered as homoaromatic,and the tetrazine ring has an obvious unsymmetrical boat conformation.It is obvious that the C6-methyl was in the deshielded(equatorial) position and the methine proton was in the shielded position (axial position).3.It was found that 3-aryl-6-methyl-1,6-dihydro-1,2,4,5-tetrazines can smoothly proceed in chloroform under alkali condition at room temperature with aryl isocyanates, chloroformates and acyl chlorides,which afforded thirty-eight new compounds of 1-acyl-3-aryl-6-methyl-1,6-dihydro-1,2,4,5-tetrazines with the yields in 41%～93%. The results of experiment show that pyridine is a good acid binding agent;and the chloroformates and acyl chlorides proved less reactive than the substituted phenyl isocyanates in this reaction.By X-ray crystalographic analysis,it could be considered that these compounds also have homoaromaticity,and in which it can be see that the C6-methyl was in the deshielded(equatorial) position and the methine proton was in the shielded position(axial position),which showed an opposite situation of 1,6-dihydro-1,2,4,5-tetrazines.This is a result of the conformational inversion of the tetrazine ring.4.6-methyl-3-phenyl-1,6-dihydro-1,2,4,5-tetrazine was stable in alkali solution at room temperature in a period of time and was decomposed gradually to form 1,2-dibenzylidene-hydrazine.Since it was stable in a period of time,a new method for synthesis of 1-alkyl-1,6-dihydro-1,2,4,5-tetrazines have been developed.The starting 1,6-dihydro-1,2,4,5-tetrazine can be alkylated with alkyl halides in methanol and lithium hydroxide monohydrate as a base at room temperature to obtain eleven new compounds of 1-alkyl-6-methyl-3-aryl-1,6-dihydro-1,2,4,5-tetrazines in moderate to good yields.Compared the spectra of 1H NMR of these products with that of 3-phenyl-6-methyl-1, 6-dihydro-1,2,4,5-tetrazine,it can be see that the conformation of these products didn’t inversed.This result also confirmed that the conformational inversion was caused by the effect of steric hindrance of the carbonyl group.5.From the spectra of ~1H NMR,it was found that the double hydrogen atoms on the methylene substituted on N1 position gave unconventional coupling split,which may be resulted from the existence of chiral carbon(C6).The crystal structures proved that 3-aryl-6-methyl-1,6-dihydro-1,2,4,5-tetrazines and their derivatives do exsist the pair of enantiomers taking C6 as chiral center.It was also found that the degree of coupling split had some relationship with the distance between the methylene and C6 as well as the substituted position on the benzyl group.