2-Amino-5-chlorophenyl-1H-pyrazole-Directed Pd(?) Catalysis:Nitrooxylation Of Unactivated ?-C(sp~3)-H Bonds

In organic compounds,chemical groups affect the properties and uses of compounds.Organic nitrate esters are an important class of compounds,which has a wide range of applications in the fields of medical drugs and energetic materials.Traditional methods for the synthesis of organic nitrate esters has several drawbacks,including poor functional group tolerance and harsh reaction conditions.Herein,this scheme report a Pd-catalyzed nitrooxylation of unactivated?-C(sp³)-H bonds under mild condition.The main contents of the scheme are as follows:First of all,this scheme uses aniline pyrazole-directed carboxylic acid as the substrate,and synthesizes the nitrooxylated product under the catalysis of transition metal palladium.Based on the realization of the nitrooxylated reaction,a condition optimization experiment was carried out,and the optimal conditions for the nitrooxylation of unactivated?-C(sp³)-H bonds were successfully explored.The desired product was obtained in 69%yield,with palladium acetate as catalyst,aluminum nitrate nonahydrate as nitrooxylation agent and oxidant,and benzotrifluoride as the solvent,the reaction was carried out at 100°C for 24hours.Subsequently,17 substrates expansion experiments were completed under optimal reaction conditions,and the carboxylic acid substrates containing various functional groups were obtained in high yield.The substrates and products were characterized by ¹H NMR,¹³C NMR and HRMS.To gain more insight into the mechanism,a range of mechanism experiments were conducted.According to the experimental results and previous related work,the possible mechanism of this paper was proposed:Firstly,the substrate undergoes concerted metallation-deprotonation in the presence of Palladium acetate catalyst to obtain divalent palladium intermediate.Then divalent palladium intermediate was converted into the tetravalent palladium intermediate by oxidative addition under the action of aluminum nitrate.Finally,the desired product was obtained by reduction elimination,the cycle of catalyst was completed at the same time.In addition,this paper also studies the derivatization of nitrooxylated product,and successfully transforms nitrooxylated product into hydroxyl compounds and lactam compounds,which provides a certain reference for the follow-up research.