Cyclization Of Diethyl-2-Acetamido-2-[2-(4-Octylphenyl)Ethyl]Malonate

Oxazole compounds are one kind of important compounds in heterocyclic chemistry, but they seldom exist in the nature. In addition, the synthesis of them is very difficult until the emergence of penicillin which facilitated the development of such kind of oxazole compounds.Oxazole compounds'core is an unsaturated five-membered ring including a nitrogen atom and oxygen atom. They are quite easy to be resolved in water,ethanol,diethyl ether etc. Because of their weak alkalinity, they can not make the litmus paper change the color. Their activities are much closed to furan which can open the ring and have [4+2] addition reaction easily. The atom of nitrogen impedes its electrophilic substitution reaction, but it makes the nucleophilic substitution in 2-position much easier. Although oxazole is heterocyclic aromatic hydrocarbon, due to its delocalization in its ring, its aromaticity is weaker than furan. Oxazole compounds can take part in many kinds of reactions such as: salt forming reaction,metallation,electrophilic reaction,nucleophilic and the addition reaction.In our lives, the oxazole compounds have many applications. For example: In the drug domain, oxaprozin tablets can relieve the pain and eliminate inflammation; in industry, 4,4'-dioxazole-2-distyrene has strong fluorescence which can be used as the fluorescent material; in agriculture, fenoxaprop-p-ethyl can be used as a herbicide. Although oxazole compounds play an important role in our lives, the research on them is not enough.Since the synthesis of oxazole in 1947, people have accumulated many methods to synthesize oxazole which can be distributed into three types: type one is the intra-cyclization of one compound which should have both the esterfunction and the amide under the catalysis of polyphosphoric acid; type two is the condensation ofα-halogeno-carbonyl compound and amide; type three is the Fischer synthesis of oxazole which makes the HCl go through the solution of Mandelonitrile and benzaldehyde, but this way is only suitable for the aromatic aldehyde.The purpose of this paper is to find a new way to synthesize tetralin-oxazole compound which has few research on it. In tradition, the synthesis of it is made by tetralin derivates. We referred to the synthesis of pyridonecarboxylic compounds and the classic synthetic way of tetralin-oxazole and found that both of them were happened under the catalysis of Lewis acid. On the basis of it, we propose a new way to synthesize retralin-oxazole using diethyl 2-acetamido-2-[2-(4-octylphenyl)ethyl]malonate as the raw material. This method is totally new which has never been reported. We use poiyphosphoric acid as the catalyst and solution to have the cyclization under 110℃. We get two main compounds in this reaction. After analysis using 1H NMR,13C NMR,MS and IR, we confirm their structure. One of them is the tetralin-oxazole derivate and the yield is 62%. The synthesis of it explains that the success of the original design of the synthetic route. The other compound is tetralone and the yield is 18%. It is one important intermediate in chemical industry. This way can provide a new way to synthesize such compound.On the basis of experiment, we propose the possible mechanism of the cyclization. First, diethyl 2-acetamido-2-[2-(4-octylphenyl)ethyl]malonate has the Fridedl-Crafts acylation under the catalysis of poiyphosphoric acid, then hydrolysis,decarboxylation,the change of ketone-enolic form,condensation and then dehydration to get the target compound of oxazole. We use one step to have two consecutive cyclizations and get the oxazole compound. No matter the synthesis of the raw material or the synthesis of the target compound is very simple. It provides one totally new way to synthesize such compounds and have a promising development.