Table substituent parameters

Several Hansch-Leo n substituent parameters denved from octanol-water partition coefficients (P), = log p (ce sX) - log P (C H ), are hsted m Table 9... 

The previous analysis by the dual substituent parameter equation of substituent effects in the naphthalene series provided support for the scale, especially for sets involving nonconjugating positions (2p). The available data yield six basis sets which presumably give a critical analysis and, in particular, provide distinctions between conjugative (three sets) and nonconjugative positions (three sets). The results (using the earlier symbolism (2p)) are given in Table X. 

X", n, SD, / values obtained for each on fittings with the values of Table V. In Table XII, the comparative values of SD and SD/RMS are given for each of these reactions for fittings to all of the various substituent parameters. As expected from the fact that X values are small (. 3-.5), the meta data are not discriminating. Three of the eleven meta basis sets are best fit by the values (Table XII) two sets are essentially equally well fit by and crj (A) two sets are best fit by two sets are best fit by itd two sets are best fitted... 

These sets of substituent parameters are dependent upon the Oj values of Table I in one respect only namely, in the p/ and values generated by the preliminary fittings as the constraints. This procedure then allows for the detection of any clearly errant substituent parameters. For example, the finite 0/ values for the CF3 substituent have been questioned (29) on the basis of an errant (too small) value of Oj. However, the substituent parameters generated from individual reaction series by this procedure (cf. Table XXV) are in good accord with the values of Table I. Accordingly, the results of this treatment provide no evidence of inadequate or errant o/values. 

From the and p values of Tables II, VI, and VIII, data for additional substituents may be used to obtain the various Or parameters. A number of secondary substituent parameters so derived are summarized in Table XXVI. The Or values are rounded values obtained from the indicated data. The oj parameters are based upon m-FC6H4X F-nmr shifts. The results in Table II are untested, of course, and should be used with due caution. 

Table XIV lists comparative SD and /values for fittings of all the sets of Table Xlll with each of the scales of Table V, the FandR values of Swain, and with the single substituent parameter treatment, po y These statistics, coupled with structural considerations, we believe support the usefulness and uniqueness of a scale of limited generality. In general, the / values of Table XIV for the Or scale are smaller than those of the other scales by factors of from 2 to 10. The root-mean-square F values for the other scales are from 2.25 (< j (BA)) to 3 to 4 (S L,, cr (yv)) times that for. Because this analysis has demonstrated that Swain s F and R are generally inferior for the discriminating data for all four types, there appears little to encourage proliferation of these parameters.

A table of correlations between seven physicochemical substituent parameters for 90 chemical substituent groups has been reported by Hansch et al. [39]. The parameters include lipophilicity (log P), molar refractivity MR), molecular weight MW), Hammett s electronic parameters (a and o ), and the field and resonance parameters of Swain and Lupton F and R). 

Fig. 37.2. Principal components loading plot of 7 physicochemical substituent parameters, as obtained from the correlations in Table 37.5 [39,40]. The horizontal and vertical axes account for 46 and 31%, respectively, of the correlations. Most of the residual correlation is along the perpendicular to the plane of the diagram. The line segments define clusters of parameters that have been computed by means of cluster analysis.

For cyclopropanations with ethyl diazoacetate, a rather weak influence of the olefin structure has been noted 59 60, (Table 7). The preference for the sterically less crowded cyclopropane is more marked for 1,2-disubstituted than for 1,1-disubstituted olefins. The influence of steric factors becomes obvious from the fact that the ratio Z-36/E-36, obtained upon cyclopropanation of silyl enol ethers 35, parallels Knorr s 90> empirical substituent parameter A.d of the group R 60). These ZjE ratios, however, do not represent the thermodynamic equilibrium of both diastereomers. 

Reynolds and coworkers156 based a similar operation on 13C substituent chemical shifts of meta- and para-substituted styrenes. Iterative multiple regression was used for the redefinition of the 07 and crjj scales. The authors also took the opportunity to replace the symbol 07 by op, having become convinced that the so-called inductive effect was entirely a field effect (see the present author s discussion of this matter76). The authors presented an extensive table in which their values of the substituent parameters are compared with those obtained by other authors. Their cr value of 0.144 for NO2 essentially confirmed the various values of about 0.15 already mentioned and their 07 value of 0.651 essentially confirmed the various values of about 0.65. 

Structural parameters of selected mononuclear complexes containing heteroatomic 7i-donor-substituted allenylidene ligands are summarized in Table 1. When these data are compared to those reported for related complexes bearing conventional alkyl or aryl substituents (see Table 1 of chapter All-Carbon-Substituted Allenylidene and Related Cumulenylidene Ligands ), a lengthening of the M=C bond... 

The influence of substituents, including aza, on reactivity of the nitrogen atom in such systems have been considered in detail1 6,7,47 102,188 189 and may be correlated with Dewar—Grisdale calculations [Eq. (2)],6 33-190-192 or dual-substituent parameter [Eqs. (3) and (4)].6,7,47,188-190 Thus, analysis6 of pXa s (HzO, 25°) of substituted quinolinium and isoquinolinium cations according to Eq. (20) gave the results shown in Table V, where they are compared with those for substituted naphthoic acids (aq. EtOH, 25°). 

From the pK values of 2,6-dimethyl-4-pyrone and -4-thiapyrone and the p value of —1.75 for the correlation of 4-substituted 3,5-dimethylphenols, 07 values of 5.8 and 5.4 were derived for the heteroatoms 0+ and S+, respectively, while values of of 3.0 and 3.2, respectively, similarly uniquely large, were calculated from hydrogen exchange data.80 Table VII gives substituent parameters for the total effect of some six-membered rings. 

C chemical shifts in aromatic compounds are dependent on the polarity of the substituent. Appendix 3, Table A3.14 shows the substituent effects for a range of substituted benzenes. The 13C spectra of substituted benzenes can often be interpreted on the basis of these substituent parameters in association with data from off-resonance decoupled spectra. 

Conjugation of the nitrogen lone pair with the adjacent phosphoryl or carbonyl function was tested by the 13C NMR parameters of the N-phosphorylated and N-acetylated aniline, as well as of their complexes with Lewis acids. (h ). The inductive and resonance constants for the neutral and charged amide groups were determined using the dual substituent parameter (dsp) approach. ( 5). Results are given in the Table. 

The 3,4-dihydroisoquinoline system is also encountered in this family of alkaloids. The assignment of chemical shifts to the aromatic carbon atoms of the substituted 3,4-dihydroisoquinolines (21-25 in Fig. 3 and Table III) followed directly from the application of the appropriate substituent parameters to the shifts reported for 20 (22) and from a consideration of the resonance effect of the carbon-nitrogen double bond. This latter point is especially evident in the methiodide salts, 24 and 25, where charge delocalization causes C-4a, C-6, and C-8 to appear at lower field than their counterparts C-8a, C-l, and C-5, respectively. Carbon-1 was readily recognized as the lowest field resonance because of its imine character. 

The absolute rate constants for ene-addition of acetone to the substituted 1,1-diphenyl-silenes 19a-e at 23 °C (affording the silyl enol ethers 53 equation 46) correlate with Hammett substituent parameters, leading to p-values of +1.5 and +1.1 in hexane and acetonitrile solution, respectively41. Table 8 lists the absolute rate constants reported for the reactions in isooctane solution, along with k /k -, values calculated as the ratio of the rate constants for reaction of acetone and acctonc-rff,. In acetonitrile the kinetic isotope effects range in magnitude from k /k y = 3.1 (i.e. 1.21 per deuterium) for the least reactive member of the series (19b) to A hA D = 1.3 (i.e. 1.04 per deuterium) for the most reactive (19e)41. Arrhenius plots for the reactions of 19a and 19e with acetone in the two solvents are shown in Figure 9, and were analysed in terms of the mechanism of equation 46. 

In contrast, the rate constants for methanol addition to the series of silicon-substituted silenes 2a-i (Table 13) do not vary in a straightforward way with either inductive io ) or resonance (o ) substituent parameters associated with the R substituent. However, a multi-parameter fit of the data to equation 64, in which Es is the steric substituent parameter of Unger and Hansch122 and p, pr and ps are the related standard reaction constants describing the individual effects of inductive, resonance and steric effects on the rate (and are the variables in the analysis), led to an excellent least-squares fit of the data (r2 = 0.965). This afforded the coefficients pr = —3.6 1.2, pi = 3.1 1.0 and ps = 0.21 0.08, where the quoted errors represent the 95% confidence limits of the analysis. Figure 11 shows a plot of the data against the function obtained from the least-squares fit (equation 65). 

Substituent effects on rate constants of base-promoted ionisation of ketones have led to the conclusion that an electron-withdrawing substituent increases the rate of ionisation, in agreement with the anionic character of the transition state. This is based chiefly on studies on halogenation and isotope exchange of aromatic ketones. Data on p-values observed by plotting ionisation rate constants versus Hammett -parameters (Table 3) for substituted... 

The results of two-parameter correlations of the 13C and 15 N NMR chemical shifts of 2-substituted 5(6)-nitrobenzimidazoles with the induction and resonance constants (a, ak) are given in Table 3.26 [688, 689], The electronic influence of substituents on the chemical shifts of carbons (and protons) in positions 4 and 7 are mainly transmitted by a resonance mechanism, C-4 being more sensitive than C-7 to the substituent effect. For positions 5 and 6 a slightly smaller contribution from the resonance component to the total transmission of substituent effects is observed. However, analysis of correlation between 5 15 N and substituent parameters indicates an approximately equal influence of the induction and resonance substituent effects on the nitro group shielding (see Table 3.26) [688, 689], When other sets of substituent constants (F and R, c, and ck, etc.) are used in the correlation the percentage ratios of resonance and inductive contributions remain unchanged. 

The results of two parameter correlations AE m and AE"m (A 1/2=E /2X-H /2H) with constants of the substituents CTjCTr, a ak", FR and CTjCTr+ (Table 3.49) show that the substituent influence on the first half-wave potential follows both induction and resonance mechanisms, the ratio of contributions of these effects being approximately equal and, practically, independent of a choice of the substituent parameters. The correlation results between AE"1/2 and substituent parameters indicate that the substituent influence is mainly achieved by the resonance mechanism (approximately 80%) (Table 3.49) [991],... 

TABLE 6.2 H Substituent Parameters (A5X, ppm) for Substituents on Tetrahedral Carbons"... 

Suppose a methylene group were connected to two of the substituent groups from Table 6.2. Could you predict the chemical shift of the methylene hydrogens If the two substituents (X and Y) exert their (de)shielding effects independently, then perhaps the chemical shift of the methylene group could be calculated by simply adding the substituent parameters of both substituents to the chemical shift of methane ... 

Vinyl hydrogens typically appear in the 8 4.5-7.0 region of the H spectrum. We can establish a list of substituent parameters for vinyl substituents (Table 6.4) similar to the one we had for methyl substituents (Table 6.2). Notice that the magnitude of a substituent s (de)shielding effect is strongly... 

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