Ortho substituents, calculation

From the understanding, provided by the calculations, of the mechanism by which lb cyclizes, what can be predicted about how the rate of this reaction might be affected by substituents on the benzene ring The substiment effects would, in fact, be expected to be small, except for possible steric effects due to substituents in the ortho positions. If both ortho positions are substimted, one would expect to see a decrease in rate, relative to unsubstituted lb. On the other hand, if only one ortho position is substituted, cyclization should be about as fast as in unsubstituted lb but cyclization should preferentially occur at the unsubstituted ortho carbon. Additional (8/8)CASPT2/6-31G calculations by Bill Kamey in our group and subsequent experiments by the Platz group confirmed these qualitative predictions about the effects of ortho substituents. 

Of particular interest are the results in Table 7 for cyclization of singlet or/Ao-cyanophenylnitrene (8c). The barrier to cyclization of 8c away from the cyano substituent to give 9c is calculated to be about the same as that for cyclization of PN, and the barrier to cyclization of 8c toward the cyano substituent to give 10c is predicted to be either about the same as (CASSCF) or slightly lower than (CASPT2) the barrier to cyclization of 8c away from the cyano group. This prediction is very different from the computational and experimental results for cyclization of ortho-methy -phenylnitrene where cyclization away from the ortho substituent is strongly preferred over cyclization toward the substituent. 

An approximation approach to study the torsonial amplitudes in biphenyls without ortho substituents using electron-diffraction data leads to rather large amplitudes216. The two molecules chosen were 33 -dibromobiphenyl and 3,5,3 5 -tetra-bromobiphenyl. The u-value for the Br3. ..Br3.-distance was calculated from the electron-diffraction data. Only the larger of the two Br3. .. Br3.-distances appeared suited for the study. Since the total u-value is composed of contributions both from the framework vibration and from the torsional motion, an estimate of the framework vibration amplitude is needed in order to obtain the rotational amplitude, a In order to estimate the framework vibration, 3,5,4 -tribromobiphenyl was studied. 

Hammett postulated that the cr values calculated for the ring substituents of a series of benzoic acids could also be valid for those ring substituents in a different series of similar aromatic compounds. This relationship has been found to be in good agreement for the meta and para substituents of a wide variety of aromatic compounds but not for their ortho substituents. The latter is believed to be due to steric hindrance and other effects, such as intramolecular hydrogen bonding. 

Calculations for ort/io-disubstituted compounds are less satisfactory because of steric or other interactions between the ortho substituents. 

These calculations show that the barriers are quite low in the unsubstituted molecule and little affected by remote substitutions. These compounds provide an interesting basic set for the study of steric barriers when ortho substituents are introduced. 

In their studies of multisubstituted aromatic compounds, Hansch and co-workers have generally summed ir and a values for individual substituents to obtain estimates of tt and a characterizing the multisubstituted derivative (10). Although tr and o- constants for ortho substituents may not be well represented by the corresponding values for para substituents, let us assume that tt(2-C1) = 7r(4-Cl) and o-(2-Cl) = o-(4-Cl) for our predictive calculation. For the disubstituted TFMS derivatives, we obtain from Table IV (in the absence of surfactant) ... 

Using the a values for ortho substituents given in Appendix 3, Table 10 calculate the pA values of the following (experimental values given in brackets) 2-chloro-4-nitrobenzoic acid (1.96), 2,6-dimethylpyridine (6.77), 2,4-dichloroanilinium ion (2.05) and 2,3,5-trichlorophenol (6.43). Hammett equations for the dissociation of substituted phenols, pyridinium ions, anilinium ions and benzoic acids are given in Appendix 4, Table 1. 

Chemical shift increments are the shifts from that of the protons of benzene (8 7.27). Thus for a CH C=0 substituent (line 26, Appendix Chart D.l), the ortho increment is +0.63, and the meta and para increments are both +0.28 (+ being at higher frequency than 8 7.27). The C-2 proton has two ortho substituents the C-4 and C-6 protons are equivalent and have ortho and para substituents the C-5 proton has two meta substituents. Thus the calculated increment for C-2 is + 1.26, for C-4 and C-6 is +0.91, and for C-5 is +0.56. The spectrum shows increments of +1.13, + 0.81, and +0.20, respectively. This agreement is adequate for determining the substitution pattern. Integration of the spectrum would show the expected ratio of 1 2 1. Furthermore, both the ortho- (with identical substituents) and para-substituted compounds would show the characteristic, symmetrical patterns of Figures... 

Aromatic tt or / values derived from meta and para substituents tend to be identical, but ortho substituents often give outlying values, e.g., when they permit internal hydrogen-bonding, lipophilicity is increased. Nevertheless, by much more complicated calculations, Fujita and Nishioka (1975) have made a special table for ortho substituents that integrate well with the meta and para values. Apart from this, these tt and / values are very sensitive to polar environments. For example, tt for chlorine substituted in benzene is 0.71, but this becomes (insertion is in all cases, meta) 0.61 in nitrobenzene, 0.68 in phenylacetic acid, 0.83 in benzoic acid (all ionizable substances are corrected for ionization), 0.98 in aniline, and 1.04 in phenol. This difference of 0.43 between extremes is increased to 0.90 when nitro-group replaces chlorine in the... 

Only one actual problem in chemistry was solved using molecular mechanics as we use it now, by hand calculations. In a series of studies, Frank Westheimer described the following situation. Ortho-substituted biphenyl molecules are generally not co-planar because of the steric interference of the ortho substituents. A typical example is 2,2 -dibromo-4,4 -dicarboxybiphenyl. Consider the two structures of this molecule shown in Reaction (1) ... 

Myers and coworkers reported an unprecedented example for catalytic decar-boxylative alkenylation of ortho-substituted benzoic acids [25]. Thus, treatment with styrene in the presence of 20 mol% of Pd(02CCF3)2 and 1.2 equiv. of Ag2COg in dimethyl formamide (DMF)/dimethyl sulfoxide (DMSO) at 80-120 C gives stUbene derivatives (Scheme 4.21). density functional theory (DFT) calculations of the reaction were performed to interpret the promotion effects of ortho-substituents on benzoic acids [26]. 

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