Fig. 6. The effectiveness test of the RSscore on Paracetamol synthetic routes analysis
Another validation example is also given here for Clobazam synthesis routes. After obtaining the reaction condense hypergraph descriptors and calculating the average RSscore of each reaction synthetic routes inFig. 7 , the average RSscore for route (a), (b) and (c) are 0.5915, 0.7493 and 0.7721, respectively. By comparing the average RSscore values of the synthetic routes, the reactions in route (b) and (c) exhibit better overall performance compared to the route (a). This demonstrates that synthetic route (b) 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 longer reaction steps and low yield (total yield can reach approximate 11%).51 Route (b) and Route (c) require fewer steps and the yield for each step in Clobazam generation are high (total yield can reach approximate 50%) which provides a methodology for the industrial production of clobazam.52,53 Through a comparison of the synthetic routes from literature results, Route (b) and Route (c) are relatively better. However, Route (b) requires hydrogenation reaction equipment, which results in higher production cost than Routes (c). According to the development of RSscore, the production cost is not considered. Therefore, the RSscore is not able to distinguish the difference between the Route (b) and Route (c). The comparation result of the synthetic routes is consistent with the conclusions obtained by RSscore, which shows that RSscore can be a better aid to the analysis of the synthetic routes.