Steric effects diazonium coupling

One circumstance that could affect the k2/k ratio is steric hindrance. Thus, diazonium coupling of 3 gave no isotope effect, while coupling of 5 gave a h/ d ratio of 6.55.8 For... 

Iodination of 2-benzyl-2-hydroxypyridine (9.101) occurs at the 6- and subsequently at the 4-position. Under similar conditions, the corresponding N-oxide gave only the 4,6-diiodo product. This does not necessarily prove that the N-oxide function is more effective in activating the 4-position steric hindrance to 6-substitution may be involved (cf. 75CHE478). Whereas both aminomethylation and diazonium coupling were easier for the N-oxide than for 9.101, the 4- 6-isomer ratio for both reactions was similar for both pyridine and its N-oxide (75CHE478). 

Diazonium coupling of 3-hydroxyquinoline and 4-hydroxyisoquinoline occur at the expected 4- and 3-positions, respectively (72BAU452). For-mylation of 6-methoxy-3-methy]benzoU/, ]cinnolines (11.117) takes place at the 7- and 9-positions (3.3 and 33%, respectively) for R = H. However, for R = Me, no 9-formylation occurs, the yield of 7-formylation is increased to 30%, and 5.5% of N-formylation occurs (8IJOU2I83). The difference between these results appears to reflect a steric effect. 

One circumstance that could affect the 2/ -1 ratio is steric hindrance. Thus, diazonium coupling of 6 gave no isotope effect, while coupling of 8 gave a kn/kj) ratio of 6.55. For steric reasons, it is much more difficult for 9 to lose a proton (it is harder for a base to approach) than it is for 7, so 2 is greater for the latter. Since no base is necessary to remove ArN2", k- does not depend on steric factors and is about the same for each. Thus the partition factor 2/ -1... 

As in the reaction of imidazole, no major isotope effect has been observed 3-deuterioindole reacts at about the same rate as indole. The diazo coupling of five-membered heteroaromatic substrates therefore appears similar to that of homocyclic compounds where, in the absence of steric hindrance, slow attack of the diazonium ion is followed by a fast proton loss.165... 

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