Amide Acetal In The Synthesis Of Heterocyclic Compounds

1,2,4-triazolin-5-one, 1,2,4-triazole, 1,4,7,10-tetraazacyclododecane, isoxa-zole, pyrazole, indole and their derivatives were synthesized by the reaction of formamide acetals with carbamates, amides, amine and compounds with reactive methyl or methylene. These nitrogen heterocyclic compounds with interesting pharmacological activities have been widely used in medicine, pesticides and other finechemical fields.A novel method of preparing three 1-subsituted-1,2,4-triazolin-5-ones and their mother ring was preferred by the reaction of DMF-DMA and ethyl carbamate[n (DMF-DMA ) : n (ethyl carbamate) =1:1 ], cyclization of the intermediate in acetic acid at 100C for 2h in 76% yield. 1,5-disubstituted-1,2,4-triazole was prepared by the reaction of DMF dimethyl acetal and N- nosubstituted amides. The cyclized reaction was carried out by reactive materials at molar ratio 1:1, in 70% acetic acid solution at 90C for 3h, giving 95% yield.The yield is about 40% more than the literature value of 56%. 1,4,7,10-tetraazacyclododecane (Cyclen) was synthesized by DMF-DMA and TETA through three-step procedure. The yield of "diimidazoline" intermediate was 90%. The yield of the reaction of enlarged ring and basic hydrolysis separately was 78%, 84%. The reaction of DMF diethyl acetal (DMF-DEA) with ethyl acetoacetates having reactive methylene was studied. Isopropylnol was choosed as solvent in the preparation of isoxazoles and pyrazoles, especially giving the high yield of 97.8% in preparation of 5-methyl-pyrazole-4-carboxyl-ate. Indole was prepared by DMF di-n-propyl acetal and 2-nitrotoluene having reactive methyl, which involves using DMF di-n-propyl acetal instead of DMF dimethyl acetal to improve the reaction temperature, pyrrolidine as anti-polymerization agent, and reductive cyclization. The overall yield of the two steps was 75%. Thirteen prepared compounds were characterized by IR, HNMR, MS and elemental analysis.