Synthesis Of Heterocyclic Compunds Using Tetraalkylammionium As Soluble Support

Tetraalkylammionium as soluble support combines the superiorities of solid phase synthesis such as easy separation and purification, recyclable usage, and the advantages of classical liquid phase synthesis such as homogenous reaction, high relativity, ease detection reaction procedure by routine analytic methods, so it has been widely used in organic synthesis. Based on the advantages of tetraalkylammionium as soluble support, we investigated the synthesis of heterocyclic compounds 2-aminothiophenes and 3-amino-5-aryl-2,5-dihydro-pyridazines using trimethyl-2-hydroxyethylammonium chloride as soluble support.Firstly, using trimethyl-2-hydroxyethylammonium chloride as soluble support, we synthesized 2-aminothiophenes derivatives which had the biological activity of anti-convulsive, anti-anxiety and anti-tumor. Using the hydroxy group of tetraalkylammionium as a linker, cyanoacetic acid was supported on tetraalkylammionium and obtained tetraalkylammionium supported ethyl cyanoacetate, which transformed to tetraalkylammionium support 2-aminothiophenes by reacting with sulfur and ketone/aldehyde by Gewald condensation. After a simple cleavage step, the products were obtained in pure form and good yields (55%～91%).Secondly, we investgated the synthesis of 3-amino-5-aryl-2,5-dihydro-pyri-dazines derivatives using trimethyl-2-hydroxyethylammonium chloride as soluble support. Tetraalkylammionium supported ethyl cyanoacetate as starting material reacted with armoatic aldehydes, and then treated with 1-phenylhydrazonopyruvalde-hydes to obtain tetraalkylammionium supported 3-amino-5-aryl-2,5-dihydro-pyri-d azines derivatives. After a simple cleavage step, we obtained 10 kinds of 3-amino-5-aryl-2,5-dihydro-pyri-dazines derivatives in good yields (75-82%).In conclusion,2-aminothiophenes compounds and 3-amino-5-aryl-2,5-dihydro-pyridazines compounds were synthesized using trimethyl-2-hydroxyethylammonium chloride as soluble support. The reaction could be fulfilled quickly with high purity and yield, and the operation was very simple. The structure of tetraalkylammionium has not been destroyed when it was cleaved and it could be reused just by simply washing with ether. This study expanded the application of tetraalkylammionium as a soluble support in organic synthesis, and provided a simple and efficient method to heterocyclic compounds.