Mechanism study of the N-butoxycarbonyl-2,5-dimethylpyrrole synthesis reaction based on in-situ FTIR monitoring

The reaction pathway of many Paal-Knorr reactions for pyrrolic compounds hasn’t been thoroughly studied and remains controversial. In this work, the synthesis of an important anti-ultraviolet agent N-butoxycarbonyl-2,5-dimethylpyrrole based on the Paal-Knorr reaction was studied via in-situ Fourier transform infrared (FTIR) analysis combined with density functional theory (DFT) calculation. The online spectral data were analyzed using K-means clustering in order to find the characteristic wavenumbers of intermediates. It was found that the reaction with 2,5-hexadione and butyl carbamate are more favorable to form the imine and enamine intermediates by nucleophilic addition, which is different from another Paal-Knorr reaction with 2, 5-hexadione and ethanolamine. In addition, the reaction kinetic model was established through chemometric methods, with parameters of two rate-limiting reaction steps calculated. This approach of FTIR analysis is proven to be an effective tool for mechanism study of organic synthesis.