X-Substituents

Figure 3-8 a) The dissociation of substituted benzoic acids (X = substituent), and b) the hydrolysis of benzoic acid methyl esters. 

Figure 7-2 indicates that this intramolecular assistance takes place with those compounds having substituents to the right of X = OMe = —0.78), for in this portion of the a scale compounds 8 solvolyze more rapidly than do 7. At the X = OMe member, however, the two series have essentially identical reactivities, and this behavior continues at more negative cr. It. therefore, appears that intramolecular participation by the double bond occurs when it is needed when the X substituent is sufficiently electron-donating to stabilize the cation, intramolecular assistance is not needed, so it does not occur, and the saturated and unsaturated series show the same reactivity. 

The curvature may be an artifact of a selection of nucleophiles of mixed structural types chosen to display a wide range in pAo. Buncel et al. ° varied pK by changing the solvent composition over a limited range rather than by changing the structure. They studied the reaction between X-C6H4-CT and p-nitrophenyl acetate in 40-90 mol% dimethylsulfoxide—water mixtures with just three X substituents... 

For amide enolates (X = NR2), with Z geometry, model transition state D is intrinsically favored, but, again, large X substituents favor the formation of nt/-adducts via C. Factors that influence the diastereoselectivity include the solvent, the enolate counterion and the substituent pattern of enolate and enonc. In some cases either syn- or unh-products are obtained preferentially by varying the nature of the solvent, donor atom (enolate versus thioeno-late), or counterion. Most Michael additions listed in this section have not been examined systematically in terms of diastereoselectivity and coherent transition stale models are currently not available. Similar models to those shown in A-D can be used, however all the previously mentioned factors (among others) may be critical to the stereochemical outcome of the reaction. 

In eq. (32), pi and p2 denote the percent of the product containing boron at C and, respectively. Applying the extended Hammett equation to the partial rate constants ki and k2 for the compound bearing the X substituent gives... 

The indicator variable I is assigned the value of 1 for the presence of amide derivatives and 0 for the esters. Its negative coefficient suggests that esters would be preferred over amides for this data set. nx is the calculated hydrophobic parameter of the X-substituents. Its positive coefficient suggests that the highly hydrophobic X-substituents would be preferred. 

MRx is the calculated molar refractivity of X-substituents, whereas I is an indicator variable taking the value of 1 and 0 for the presence and absence of a phenyl ring in the X-substituents. The negative sign of MRx brings out a steric effect for the X-substituents that do not appear to reach a hydrophobic surface for ttx (calculated hydrophobicity of X-substituents), r = 0.470. The indicator variable (I) with positive coefficient suggests that the presence of a phenyl ring in the X-substituents would be favorable. 

This is a parabolic relation in terms of MRx (calculated molar refractivity of X-substituents), which suggests that the inhibitory activities of quinolones (XIX) against topo II first increases with an increase in the molar refractivity of X-substituents up to an optimiun MRx of 1.84 and then decreases. 

Perhaps the most important conclusion to be drawn from results for metal atoms in groups such as 7SiL3 or -PL3+ is undetectably small (70,71). Indeed, the R2C- moiety displays hyperfine interaction with H and 13C that suggest normal planarity at carbon with essentially unit spin-density thereon, and coupling to the metal atom (specifically, 31P) is small and probably negative. This implies that spin-density is acquired by spin-polarisation of the C-M o-electrons and not by p -d delocalisation, as is so often... 

Variation of the X-substituent in (190) may be used to tune the pH at which efficient extraction occurs. For example, for the case where X = N02, the electron-withdrawing ability of this group results in more facile deprotonation of the amino proton. Thus the extraction may be performed at a lower pH than for the system with X = H. Similarly, variation of n in (190) may be used to tune the system for metal ions of different radii. 

For application in organic synthesis, the regiochemistry of insertion of carbenoids into un-symmetrical zirconacydes needs to be predictable. In the case of insertion into mono- and bicydic zirconacydopentenes where there is an wide variety of metal carbenoids insert selectively into the zirconium—alkyl bond [48,59,86], For more complex systems, the regiocon-trol has only been studied for the insertion of lithium chloroallylides (as in Section 3.3.2) [60]. Representative examples of regiocontrol relating to the insertion of lithium chloroal-lylide are shown in Fig. 3.2. 

This is the best known rearrangement reaction of phenylhydroxylamines and is an acid catalysed reaction leading principally to the formation of 4-amino phenols 37, although a little of the 2-isomers 38 are also sometimes formed. Reaction proceeds quite smoothly in relatively dilute acid at room temperature. Reaction is quite general for a range of R and X substituents. Much of the early work was carried out by Bamberger38 and the position up to 1967 has been very well reviewed39. 

A similar system, (CH3)2C=CH X, was studied by Endrysova and Kraus (55) in the gas phase in order to eliminate the possible leveling influence of a solvent. The rate data were separated in the contribution of the rate constant and of the adsorption coefficient, but both parameters showed no influence of the X substituents (series 61). A definitive answer to the problem has been published by Kieboom and van Bekum (59), who measured the hydrogenation rate of substituted 2-phenyl-3-methyl-2-butenes and substituted 3,4-dihydro-1,2-dimethylnaphtalenes on palladium in basic, neutral, and acidic media (series 62 and 63). These compounds enabled them to correlate the rate data by means of the Hammett equation and thus eliminate the troublesome steric effects. Using a series of substituents with large differences in polarity, they found relatively small electronic effects on both the rate constant and adsorption coefficient. 

The log A vs o plot is reasonably linear with no marked deviations for seven X-substituents. The value of p is 0.75 and this is much smaller than that for alkaline hydrolysis of the free... 

The nitrenium ion +NH2 has been the subject of a detailed, comprehensive calculation. Calculations on (48) with 15 different X substituents reveal a large substituent sensitivity, and also that aqueous solvation preferentially stabilizes the singlet state. This substiment sensitivity agrees with the results of a time-resolved IR study of the diphenylnitrenium ion (49), which shows that resonance contributors such as (50) and (51) are very important to the overall structure. Substituted 4-biphenyl nitrenium ions... 

Anomeric effects in ONCl systems are Uo-Oj a even though oxygen is more electronegative than chlorine N and O orbitals are similar in size and chlorine is a 3p element, thus favouring overlap between the p-type lone pair on O with the low-energy N-Cl <7 orbital. In XNY systems, occupation by Uy leads to transfer of electron density to the X substituent and the substantially higher electron affinity of chlorine will also favour this anomeric interaction rather than an Uci-cTno overlap. 

Fig. 8 Plots of half-lives for deglycosylation rates of 8-/>-X-Ph-dG adducts versus Hammett CT+ values in 0.1 N HCl at 37.2°C (a) and 0.05 M citrate buffer (pH = 4.0), /i = 0.31 M NaCl at 48.4°C (b). The X-substituent of the phenyl ring is identified next to its data point.

Fig. 9 Plots of Hammett values versus Ep/2 (volts vs. SCE) for 8-/)-X-Ph-dG adducts using (a) (T+ value for OH (—0.92) for 8- -PhOH-dG (b) it+ value for 0 (—2.30) for 8-p-PhOH-dG. The X-substituent of the phenyl ring is identified next to its data point. See 181.

Case I. First of all, we systematically introduced perturbation at coupled ff-systems (e.g. ethylene, butadiene, hexatriene and combinations of them) by substituting hydrogen for functional groups (classified by K. N. Houk as C-, Z- and X-substituents ), especially by methyl phenyl and carboxylic ester groups. We have so far introduced perturbations in the rr-system by replacing carbon atoms by heteroatoms (N and 0) in the rr-system skeleton. 

There are relatively few methods available for the preparation of condensed 1,2,3-triazines. By far the most commonly employed procedure is diazotization of a suitably ortho-substituted aniline (4) or amino-substituted heterocycle of the type 5, and examination of the different X substituents which have been used successfully in this synthesis reveals... 

Applications of the model to Ru clusters have been reported namely by Toma etal. [78] and Keister etal. [79, 80], and, for example, for the single-electron oxidation of the 48-electron complexes of the type ]Ru3(/r-H)3(/r3-CX) (CO)9 L [, expression (20) is followed [79, 80], being derived from the general Lever s equation with inclusion of a Hammett term concerning the methylidyne X substituent. The observed value of 5 m3 (0.37) (vs. the unity expected for a monometallic Ru center) is indicative of an effective delocalization of the ligand effects over the three Ru atoms [79]. 

As shown in Figure 9.2(a), an X substituent, which has a p orbital, or other suitable doubly occupied orbital that will interact with the n bond, raises the 2p orbital of the carbene, thereby increasing the separation of the 2p and ip" (a) orbitals. The ground state of an X -substituted carbene becomes a singlet, and many carbenes in this class are known. The most familiar of these are the halocarbenes. 

Figure 9.2. A carbene center interacting with (a) an X substituent, (b) a Z substituent, and (c) a C substituent.

Comparison of the conformational behavior of different C = X substituents seems necessary either to acquire a more general knowledge of s-cis/ s-trans isomerism in heterocyclic systems or for a better understanding of the behavior of acyl derivatives. 

---