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Synthesis of 6‐Nitro‐1,2,3,4‐tetrahydroquinoline: An Experimental and Theoretical Study of Regioselective Nitration
Author(s) -
Cordeiro Alessandra,
Shaw Julian,
O'Brien John,
Blanco Fernando,
Rozas Isabel
Publication year - 2011
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201001459
Subject(s) - nitration , chemistry , regioselectivity , steric effects , protonation , reagent , nitro , nitro compound , computational chemistry , organic chemistry , medicinal chemistry , combinatorial chemistry , catalysis , ion , alkyl
A revision of the literature on the nitration of tetrahydroquinolines yielded a number of inconsistencies. Thus, we have carried out a thorough study on the nitration of tetrahydroquinoline and several of its N ‐protected derivatives both experimentally and at theoretical level. Usually, nitration is carried out in acidic conditions and, thus, tetrahydroquinoline would be N ‐protonated; however, if the amino group is protected, the neutral system will be the one undergoing nitration. Different protecting groups have been explored varying, not only electronic and steric effects, but also deprotection conditions. Additionally, different reagents and reaction conditions have been investigated. From this study we have been able to achieve total regioselectivity for nitration at the 6‐position. A very detailed NMR study has been carried out to unequivocally characterise the four nitro isomers. In parallel, a computational study has been performed that is in agreement with the experimental results obtained. With this purpose, all the σ complexes of the four nitro isomers neutral and N ‐protonated have been optimized both in gas and water condensed phases by using the B3LYP/6‐31++G** level of computation.