Nucleophilic Cyclization Of Monosubstituted Urea:Synthesis Of 2,4,5-Trisubstituted Oxazoles

Compounds containing oxazole rings are widely found in natural products and are widely used in biology,chemistry,materials science and medical field.In the field of materials,oxazole compounds can be used as dye lasers,tracers and probes because of their fluorescent properties.They can also be used as useful drugs for the treatment of various diseases in biomedicine.At present,most methods for synthesizing oxazole ring structure require transition metal catalysis.In this paper,a new method for dehydration and cyclization of monosubstituted alkyl ureas to form oxazole ring by Hendrickson reagent without external metal is developed.The main content of this research is divided into the following parts:(1)Based on the existing literature methods,chiral carbamate hydrochloride and aqueous ammonia were reacted at room temperature to obtain chiral ?-aminoamide compounds in a yield of 90%.After the addition of the ligand N,N'-dimethylethylenediamine to the system,the coupling of the copper-catalyzed aryl halide and the amide nitrogen of chiral ?-aminoamide at 50? is achieved.?-Aminoamide with various functional groups is obtained in a yield of 54-96%.The reaction is complementary to the improved Ullmann-coupling reaction at low temperatures,with high yield,short time and good reproducibility.(2)We empolyed different N-aryl ?-amino amide as starting materials to synthesis the monosubstituted alkyl ureas.The volume ratio of methanol to water(1:1)was used as a solvent and acetic acid as catalyst.The reaction was carried out with potassium cyanate at 50? for 3-6 hours,giving a final yield of 76-91%.Eight new monosubstituted alkyl ureas were obtained.(3)The new N,2-diaryl-2-ureidoacetamides undergo efficient Hendrickson's reagent-mediated nucleophilic cyclization to afford seven new 2,5-diamine-4-aryloxazoles in 61-78% yield.Hendrickson reagent was generated by in situ formation of triphenylphosphine oxide and trifluoromethanesulfonic anhydride at 0 ?.It has been found that in the process of forming a closed-loop? compound,the nucleophilic attack in the urea group takes precedence over the nitrogen nucleophilic attack,thereby forming an oxazole ring instead of the imidazole ring,which is different from what we have expected.Furthermore,when the substituent of the monosubstituted alkyl urea is a ?-benzyl group,the reaction produced a corresponding cyanide compound.