3.3 Application in synthetic routes analysis

To study the effectiveness of RSscore in synthetic routes analysis, we utilized three synthetic routes of paracetamol for validation. As all three synthetic routes utilize the reaction of p-aminophenol with acetic acid at the end of paracetamol synthesis routes, its overall impact on synthetic route is negligible. After obtaining the reaction condense hypergraph descriptors and calculating the RSscore of each reaction of the synthetic routes in Fig. 6 , the RSscore for reactions in route (a) are 0.7430 and 0.5587; the RSscore for reactions in route (b) are 0.6535 and 0.4492, and the RSscore for reactions in route (c) are 0.7569 and 0.5867, respectively. By comparing the RSscore values of the reaction in the synthetic routes, the reactions in route (a) and (c) exhibit better overall performance compared to the route (b). This demonstrates that synthetic route (a) and (c) are more favorable than route (b) in terms of the combination of reaction time, yield and temperature condition.
In practical studies of these synthetic pathways, Route (a) has the advantages of short reaction time and high yield.49Route (b) requires fewer steps, but the yield for the p-aminophenol generation is low, while the handling of the waste residue generated is difficult. Therefore, this synthesis method has been abandoned by many countries.50 Route (c) could generate a high-quality of p-aminophenol, and its yield can reach 72%.50Through a comparison of synthetic routes, Routes (a) and Routes (c) are relatively better and perform little difference on reaction yield, time and temperature conditions. Although the cost for Route (c) is cheaper than Route (a), the price factor is not involved in the proposed indicator, therefore the RSscore is not able to distinguish the difference between the two routes.