Ring destabilization, aromatic

Both tetrahydroisoquinoline amides and formamidines may be successively alkylated at the l-posi-tion. The second deprotonation is somewhat less facile, however, since it entails removal of a methine proton. In applying this methodology to the synthesis of naturally occurring tetrahydroisoquinoline alkaloids, a problem is encountered. The presence of oxygen substituents on the aromatic ring destabilizes the benzylic carbanion, and since this effect is felt in the transition state, the acidity of the benzylic protons is lowered. Thus, successive alkylation of t-butylformamidines of oxygenated tetrahydroisoquinolines is not possible. To circumvent the decreased acidity, a study of the relative acidity of various N-substituted formamidines was done- that resulted in a solution to the problem. As shown in Scheme 15, successive alkylation of the methoxymethylphenylformamidine (9) is readily achieved. 

Rings can either stabilize or destabilize molecules beyond what is to be expected from a simple additivity scheme. Stabilization comes from aromatic ring systems... 

An EPR study of the monomeric 02 adducts of the Schiff base complexes of Co(bzacen)(py) (71a) and the thiobenzoyl analog Co(Sbzacen)(py) (71b) characterized the five-coordinate mono (pyridine) precursors and the six-coordinate 02 adducts.327 Increased covalency in the Co—S bonds was seen in the EPR parameters, indicative of 7r-backbonding. Substituent effects on the aromatic rings had no effect on the EPR spectra, but these were reflected in the observed redox potentials. Furthermore, the S-donors stabilize the Co ion in lower oxidation states, which was consistent with destabilization of the 02 adducts. 

The findings discussed above led Herbrandson and Cusano to the conclusion that the thermodynamically less stable diastereomer (-)-62 has the (i5)-configuration because in this structure there is a strong destabilizing interaction between the aromatic ring and the isopropyl group of the menthyl residue. X-Ray analysis of (->62 confirmed the correctness of this assignment (204). 

Substituents already bonded to an aromatic ring influence both the rate of electrophilic substitution and the position of any further substitution. The effect of a particular substituent can be predicted by a consideration of the relative stability of the first-formed arenium cation, formation of which constitutes the rate-lintiting step. In general, substituents that are electron releasing activate the ring to further substitution - they help to stabilize the arenium ion. Substituents that are electron withdrawing destabilize the arenium ion, therefore, are deactivating and hinder further substitution. 

At all levels of theory, the N-acetyl group of N-acetyl-N-arylnitrenium ions is rotated out of the plane of the aromatic ring, although to different extents." The N-acetyl group destabilizes the ion by ca. 20 kcal/mol relative to an N-methyl substituent in comparison with the neutral amide and amine precursors. This destabilization was attributed by Ford and Herman to loss of resonance in the amide precursor on going to the nitrenium ion, not to inductive destabilization of the ion by the acyl group. 

The much higher reactivity of hexahelicene compared to phenanthrene as demonstrated in competition experiments169) and apparent from the f-values170) is in line with the regular increase in reactivity in the series phenanthrene, benzo[c]phenan-threne, pentahelicene, hexahelicene. It demonstrates the effect of the increasing distortion of the aromatic rings, what destabilizes the ground state. 

Type A systems seem to behave as two separate aromatic rings, since there is a good deal of evidence for a lack of interaction between the two parts. Compounds with a central double bond (e.g., 482 and 483) are more stable than, for example, 484, at least when one of the heteroatoms (X and Y) is sulfur [compare 282b (Section IV,A,1) and 89 (Section V,B)]. Peri-interactions between free lone pairs can destabilize a system. 

Coloumbic repulsive effects are thought to destabilize the o- or m-dibro-monium ions. Mixed dihalonium ions (248) have also been prepared. Alkylaiylchloronium ions however could not be prepared under these conditions due to facile aromatic ring alkylation. 

---