Theoretical Study On The Synthesis And Isomerization Of Thiotriazinone

With a large market damand, thiotriazinone is an intermediate in thesynthesis of semi-synthetic ceftriaxone. Presently, the production technologyof thiotriazinone is still to be improved in domestic. It is very significant tostudy thiotriazinone both experimentally and theoretically. In this work, themolecular structures and spectroscopic properties of the four isomers ofthiotriazinone (denoted as TTZ1, TTZ2, TTZ3and TTZ4, respectively) werestudied by quantum chemistry method, as well as mechanisms of its synthesisand isomerization.Firstly, single crystals of thiotriazinone were cultivated in differentsolvents. Three single crystal samples were used for single-crystal X-raydiffraction analysis. The three results were the same as TTZ1. Then, thestructural optimizations and frequency calculations of the four isomers werecarried out by B3LYP and HF methods, respectively, with the6-311++G(d,p)basis set. The theoretical structural parameters of TTZ1were in goodagreement with the experimentally measured values. According to the resultsof single-crystal diffraction and the calculated total energies of the fourmolecules, it could be inferred that thiotriazinone most probably existed asTTZ1. Besides, IR and NMR spectra of both single crystal and raw materialsamples of TTZ1were measured. The results of the two samples were thesame. The scaled frequencies showed good agreement with the experimental wavenumbers. The13C NMR and1H NMR chemical shifts were obtainedusing a higher basis set6-311++G(2d,2p), in accordance with the experimentalresults. Based on the optimized structures by B3LYP method, the frontiermolecular orbitals and molecular electrostatic potential (MEP) were analysed.The values of the energy separations between the frontier molecular orbitalsgave significant information about these compounds. The MEP maps showedthat the negative potential sites were on electronegative oxygen atoms and thepositive potential sites were mostly around the hydrogen atoms.Secondly, reaction mechanisms of the synthesis of thiotriazinone werestudied at the B3LYP/6-311G(d,p) level. The synthesis methods includedintramolecular cyclization with1-oxamoylthiosemicarbazide andintermolecular cyclization with2-methylthiosemicarbazide and diethyl oxalate.It can be concluded that the main reaction pathway for intramolecularcyclization was cyclization through dealcoholization after the transfer of Hatom. The activation energy for the process of H transfer was distinctlylowered under the catalysis of DBU. As to intermolecular cyclization, themain reaction pathway contained condensation, dealcoholization, cyclization,dealcoholization, isomerization. And the rate-determining step wascyclization.Finally, reaction mechanisms of isomerization among the four isomers ofthiotriazinone were researched. It can be concluded that the isomerization ofthiotriazinone was realized through the transfer of the active H12and H15atoms, accompanied the rotation of methyl group. The activation energybarrier of the conversion of TTZ2to TTZ1was relatively higher, and it is alittle hard to realize. The activation energy barrier of the conversion of TTZ4to TTZ2was relatively lower, and it is easy to realize.