The Mills-Nixon Effect

2 The Mills-Nixon Effect The Mills-Nixon effect is bond localization 

The idea behind bond localization in annelated benzenes is exemplified by compound 66, tricyclopropabenzene. Of the two standard Kekule structures of 66, one places the double bonds within the three-member ring (endo) and the other places the double bonds outside (exo) of the small ring. Since cyclopropene is much more strained than cyclopropane, the avoidance of strain energy suggests that the double bonds might be localized into the exo positions. Compounds 66 and 67 are the prime test subjects for this idea of strain-induced bond localization (SIBL).  

Both 66 and 67 have been examined with a variety of computational techniques, from to CASSCF to The X-ray crystal structure of 67 

2427 A when the C-C-H angle is 90°. Stanger found that there was a correlation between the distortion angle a, where a = (120° - c-c-h)  

While the DFT computations indicate a smaller bond localization that predicted at HF/3-21G, distinct bond localization does result from C-C-H angular distortion from the normal 120° value. 

---

A WAVE-MECHANICAL TREATMENT OF THE MILLS-NIXON EFFECT... 

FIGURE 6.12 Traditional application of the Mills-Nixon effect theory to a-tocopherol-type henzopyranols and benzofuranols, having an anullation angle sum of (a + (3). 

Behan, J. M. Dean, F. M. Johnstone, R. A. W. Photoelectron spectra of cyclic aromatic ethers the question of the Mills-Nixon effect. Tetrahedron 1976, 32, 167-171. 

Taylor has collected the above and similar data and compared the ratio of reactivities of the ortho and para positions of compounds of type 19 (expressed as log/odog/p) with the ratio of reactivities of the equivalent positions, a and c, in compounds of type 20 and found that the latter ratio was lower, i.e., a relative increase in the reactivity of the para position (c) has occurred upon ring formation. This fall in the ratio log fa log fc increases along the series X = S < 0 (< NH < CHg) in 20. As this trend parallels the increase in strain in the fused bridging ring it was argued that ring strain was the primary cause of the reduction in ratio. Position a is a-aromatic and position c is j8-aromatic therefore the above concept represents an extension by Taylor of an earlier explanation of the Mills-Nixon effect in indane. Further substitution... 

This paper records the results of a similar study of the bond structure of tetrahydronaphthalene and a comparison of these results with our earlier work on indan and o-xylene [lc], thus permitting a rather comprehensive evaluation of the Mills-Nixon effect. What is believed to be a novel steric effect on intramolecular hydrogen bonding also will be described. 

Work on the Mills-Nixon effect has been reviewed by Badger [2]. Most of the experimental work done in this field has involved a study of relative chemical reactivities and hence is subject to the severe limitations mentioned earlier [ lc]. From a study of the ease with which the benzoates of isomeric hydroxy-5,6,7,8-tetrahydroacetonaphthones underwent the Baker-Venkataraman transformation O Farrell et ah [3] recently concluded that the 1,2-bond of 5,6,7,8-tetrahydro-naphthalene has a higher bond order than the 2,3-bond. Similar work also led these authors to conclude that the 4,5-bond in indan is of higher order than the 5,6-bond. These workers did not attempt to assess the extent of the difference in bond order presumably exhibited by the bonds in question. 

In the case of 3(5),4-polymethylenepyrazoles (91JHC647), the tautomeric equilibrium is directed by the Mills-Nixon effect thus, the 3,4-trimethylene tautomer (201) is more stable than the 4,5-one (200) (AG = 1.3 kcal mol-1) (94NJC269). 

Advances in spectroscopic and crystallographic techniques, and in computational methods, have allowed for detailed physical and theoretical analyses of the cycloproparenes. Central to a consideration of this interesting class of compounds is their role in debate over the Mills-Nixon effect—the concept of bond localization within the aromatic ring. 

Unsymmetrical /i-dikctoncs can form two /i-kcto—cnol tautomers, (90a), (90b). The corresponding N//-pyrazolcs—readily synthesized from the diketones—exhibit annular tautomerism, (91a), (91b). These tautomerisms have been probed via AMI semiempirical calculations that show that the two phenomena are related 135 in each case the position of equilibrium is strongly influenced by whether or not the CC double bond is part of (another) ring system (the Mills-Nixon effect). 

The Mills-Nixon effect (42 is a previous example) is a very controversial principle according to which the structures (resonance forms) with an endo single bond should be favored [52], Some authors reject its existence [53-55] while others believe firmly in it [56-61], We have proposed that there is some parallelism between the resonance forms of the classical Mills-Nixon 47 effect and the tautomeric forms of some heterocyclic compounds 48. 

Obviously the annular tautomerism of, for instance pyrazoles, and the resonance forms of 1,2-dihydrocyclobutabenzene are fundamentally different, but one can assume that the experimentally measurable equilibrium constant in 48 will reflect the Mills-Nixon effect [62-65], Calculations show that the effect should be very considerable with small rings (cyclobutane, 48, cyclopropane, 42) that are difficult to synthesize. However, we have succeeded in preparing compound 49 that exists as 49a, as predicted by the Mills-Nixon effect [65],... 

Attempts to localize the double bonds of the benzene ring in a Kekule-like structure have been made with some success by the groups of Vollhardt [57] and of Frank and Siegel [58]. This was reminiscent of the Mills-Nixon effect predicted in the 1930 s, although the partial localization has nothing to do with the tautomeric equilibrium in benzene argued by Kekule. 

The Mills - Nixon Effect Fallacies, Facts and Chemical Relevance... 

The Mills—Nixon Effect The First Experimental Result and Theoretical Interpretation by Sutton and Pauling... 

The Mills -Nixon effect is a consequence of the angular strain and the accompanying cr-rehybridization of the junction carbon atoms [18]. In other words a- and 7r-contributions should be dissected and treated separately. Additionally, the cr-effect is perhaps dramatic in some nonexisting model systems, where severe bond bending takes place [19], but it is rather small in real fused molecular systems, where bentbonding occurs to a much lesser extent [20]. 

There are molecular systems exhibiting 7r-bond fixation patterns that are entirely opposite to that induced by the Mills-Nixon effect [82,83,67]. Typical examples of this kind are provided by benzoborirene 33 and benzocyclopropenyl cation 34 (Fig. 19) These compounds represent extended 7r-systems relative to benzene itself since they encompass now empty 7r-orbitals at B and C+ atoms, respectively. The structural parameters offered by HF/6-31G [82] and MP2(fc)/6-31G [43] models are given in Table 10. Both molecules are planar. A salient feature of the aromatic CC bonds is their stretching relative to benzene at ortho and para positions. In contrast, meta bonds are more localized and shortened. Another striking property is a pronounced delocalization within the three-membered ring (aromatic pattern involving 27t electrons) as easily visualized by the resonance structures shown in Scheme 4. The same resonance mechanism is operative in benzocyclopropenyl cation. 

Since Mills and Nixon studied in their original paper hydroxy derivates of fused aromatic systems like /3-hydroxyindan [1], we examined a series of model compounds possessing OH group attached at the /3-position [14], It was found that the hydroxy group exerted overwhelming influence on the electrophilic susceptibility of the aromatic carbons by substantial activation of its ortho positions. However, the free /3 position is the most active one because of the Mills-Nixon effect, which amplifies the OH inductive effect. Hence the selectivity in the electrophilic substitution reactions is governed once again by the MN effect [14]. 

---