E at and thiophene ioiodine-bearing carbon (three.633 (Figure 8C). dine-bearing carbon (three.633 (FigureE

E at and thiophene ioiodine-bearing carbon (three.633 (Figure 8C). dine-bearing carbon (three.633 (Figure
E at and thiophene ioiodine-bearing carbon (three.633 (Figure 8C). dine-bearing carbon (three.633 (Figure 8C).Molecules 2021, 26, x FOR PEER REVIEW11 ofFigure 7. ORTEP diagrams (30 probability) of 3a, 3a, 3g, 3g and 3k. Figure 7. ORTEP diagrams (30 probability) of 3a, 3a , 3g, 3g and 3k .Figure eight. Cont.Molecules 2021, 26,11 ofFigure Halogen and chalcogen bond networks observed for 3a (A) and 3g (B), respectively; brief Figure eight.eight. Halogen and chalcogen bond networks observed for 3a (A) and 3g (B), respectively; short make contact with involving iodine atoms for 3g (C). make contact with involving iodine atoms for 3g (C).2.three. Direct Iodination ofof RP101988 Biological Activity 1-arylated 7-Azaindoles two.three. Direct Iodination 1-Arylated 7-Azaindoles The incorporation of iodine atoms at the 3-position of 7-azaindole is often utilized toto The incorporation of iodine atoms the 3-position of 7-azaindole may be made use of inintroduce unique aryl or heteroaryl groups [604], as well as other functions [8,65]. Our troduce distinctive heteroaryl groups [604], at the same time as other functions [8,65]. Our objective in this component isis to predict the outcome of this aromatic electrophilic substitution objective within this aspect to predict the outcome of this aromatic electrophilic substitution (SE Ar) within the case of 1-arylated 7-azaindoles. Certainly, ifif 7-azaindole can be effortlessly iodinated (SEAr) within the case of 1-arylated 7-azaindoles. Indeed, 7-azaindole could be easily iodinated at its 3-position in in DMF containing iodine soon after treatmentpotassium hydroxide [43], the at its 3-position DMF containing iodine just after treatment by by potassium hydroxide [43], behavior of 1-aryl-7-azaindoles has only been been the topic of handful of research. the behavior of 1-aryl-7-azaindoles has only the subject of very BSJ-01-175 Formula really few studies. Liu, Xu and coworkers showed in 2014, in the course of the rhodium-catalyzed chlorination Liu, Xu and coworkers showed in 2014, throughout the rhodium-catalyzed chlorination of 7-azaindoles, that 3-iodo-1-phenyl-7-azaindole may be obtained by reacting 1a with of 7-azaindoles, that 3-iodo-1-phenyl-7-azaindole may very well be obtained by reacting 1a with N-iodosuccinimide (NIS; 11 equiv) and potassium hydroxide (three equiv) in acetonitrile at rt N-iodosuccinimide (NIS; equiv) and potassium hydroxide (3 equiv) in acetonitrile at rt for 11 h h [66]. Inspired by their protocol, we replaced NIS with iodine and isolated having a for 11 [66]. Inspired by their protocol, we replaced NIS with iodine and isolated 1a 1a with yield of 65 65 (Table three, entry 1).present reaction takes spot at the carbon carbon internet site posa yield of (Table 3, entry 1). The The present reaction takes spot in the internet site possessing probably the most the most negativecharge (C charge; charge; Figure 9). Anotherto rationalize the sessing negative atomic atomic charge (C Figure 9). Another way method to rationalize regioselectivity of SE Ar reactions [67,68] should be to use to work with Fukui’s notion (an aromatic comthe regioselectivity of SEAr reactions [67,68] is Fukui’s idea (an aromatic compound reacts with an electrophile at its carbon having the highest orbital coefficient of HOMO pound reacts with an electrophile at its carbon possessing the highest orbital coefficient 34 of Molecules 2021, 26, x FOR PEER Review 12 of in absolute value) [69] and thus to calculate the HOMO coefficients by applying H kel’s HOMO in absolute value) [69] and hence to calculate the HOMO coefficients by applying theory [702] (Figure 9).(Figure present case, both approaches convergeconvergeatoward H kel’s theory [702] In th.