Effect of 7-substituents

In the preceding section, we saw that a substituent influences both the rate and distribution of products in electrophilic aromatic substitution reactions. The abihty of a substituent either to donate or withdraw electron density from the aromatic ring determines both the rate of the reaction and the product distribution. Let s consider the effect of a group, G, on the electron density of the benzene ring. 

If G is an electron-donating group, the ring gains electron density 

If G is a withdrawing group, the ring loses electron density 

We have seen that alkyl groups stabilize double bonds and carbocations by an inductive effect. We have also seen that an sp -hybridized carbon is electron withdrawing with respect to an sp -hybridized carbon. Therefore, it follows that alkyl groups also transfer electron density to a benzene ring by an inductive effect. 

An alkyl group donates electron density to the ring by an inductive effect 

Unlike the carbonyl linkage, the carbon-carbon double bond undergoes polymerization by both radical and ionic initiators. The difference arises because the re-bond of a vinyl monomer can respond appropriately to the initiator species by either homolytic or heterolytic bond breakage  

A wide range of carbon-carbon double bonds undergo chain polymerization. Table 3-1 shows monomers with alkyl, alkenyl, aryl, halogen, alkoxy, ester, amide, nitrile, and heterocyclic substituents on the alkene double bond. 

Whether a vinyl monomer polymerizes by radical, anionic, or cationic initiators depends on the inductive and resonance characteristics of the substituent(s) present. The effect of the 

The alkoxy substituent allows a delocalization of the positive charge. If the substituent were not present (e.g., in ethylene), the positive charge would be localized on the single a-carbon atom. The presence of the alkoxy group leads to stabilization of the carbocation by delocalization of the positive charge over two atoms—the carbon and the oxygen. Similar delocalization effects occur with phenyl, vinyl, and alkyl substituents, for example, for styrene polymerization  

Thus monomers such as isobutylene, styrene, methyl vinyl ether, and isoprene undergo polymerization by cationic initiators. The effect of alkyl groups in facilitating cationic polymerization is weak, and it is only the 1,1-dialkyl alkenes that undergo cationic polymerization. 

Gronowitz first applied the modern electronic theories of organic chemistry to elucidating the directing effects of substituents in the thiophene ring and has summarized concepts and experimental data in a recent review. The same rules can be extended without appreciable modifications to the other monocyclic systems furan, selenophene, and pyrrole. 

Selenophene is very similar in chemical behavior to thiophene therefore, it is not surprising that also here a 2-alkyl group directs the substitution preferentially to C-5. This has been observed in acetylation, chloromethylation, aminomethylation, and for-mylation of 2-methylselenophene. 

262 Ya. L. Gol dfarb and I. S. Korsakova, Bull. Acad. Sci. USSR Div. Chem. 481 (1954) CTiem. Ahstr. 49, 9615d (1965). 

Since the a-directing power is more pronounced in furan than in thiophene (see Section III,A, 2), the preference for substitution at C-5 is here reinforced. Substitution in 2-alkylfurans actually occurs at this position in all cases and no detectable formation of other isomers is observed.  

In pyrrole the a )3 reactivity ratio is much smaller than in the other 5-membered rings (see Section III,A, 2) here the formation of a relatively larger amount of 3-substituted isomer could be expected. Actually, the 5-substituted 2-alkyl derivative appears to be the main product in all the electrophilic substitutions of the 2-alkylpyrroles in some cases, as in the reactions with trifluoroacetic anhydride and acetyl trifluoroacetate, the 5-substituted isomer is apparently the only product formed. 

2- alkyl 3-substituted isomers are also formed in some cases, but only in the nitration of 2-methylthiophene are appreciable amounts (30%) of 3-substitution obtained.264 

---

The term p is a reaction constant and is mathematically evaluated for a particular reaction by plotting log kjkQ against a. The slope of the straight lines is p, and reflects the sensitivity of the reaction under study to effects of substituents. The value of p is obviously affected by temperature, solvent changes, etc. 

Effects of substituent on the regiochemistry of the 5-hexenyl radical cyclization... 

The effect of substituents on the rate of the reaction catalysed by different metal ions has also been studied Correlation with resulted in perfectly linear Hammett plots. Now the p-values for the four Lewis-acids are of comparable magnitude and do not follow the Irving-Williams order. Note tlrat the substituents have opposing effects on complexation, which is favoured by electron donating substituents, and reactivity, which is increased by electron withdrawirg substituents. The effect on the reactivity is clearly more pronounced than the effect on the complexation equilibrium. 

Table 2.10 shows the effect of substituents on the endo-exo ratio. Under homogeneous conditions there is hardly any substituent effect on the selectivity. Consequently the substituents must have equal effects on the Gibbs energies of the endo and the exo activated complex. 

Recent investigation of the effect of substituents in the para position of the phenylalanine ligand on the stability of the ternary complexes has revealed the secpience Br > OH > Q NH2 > H > F". Interestingly, analysis of CD spectra indicates a reduction of the arene-arene interaction" upon addition of 1,4-dioxane to aqueous solutions of the mixed-ligand complexes, in disagreement with previous observations by Sigel" . 

We have also analysed the effect of substituents in the dienophile on (1) the coordination behaviour... 

The relative basicities of aromatic hydrocarbons, as represented by the equilibrium constants for their protonation in mixtures of hydrogen fluoride and boron trifluoride, have been measured. The effects of substituents upon these basicities resemble their effects upon the rates of electrophilic substitutions a linear relationship exists between the logarithms of the relative basicities and the logarithms of the relative rate constants for various substitutions, such as chlorination and... 

QUANTITATIVE CORRELATIONS OF SUBSTITUENT EFFECTS The theories outlined above are concerned with the way in which substituents modify the reactivity of the aromatic nucleus. An alternative approach to the effects of substituents is provided by quantitative... 

There were two schools of thought concerning attempts to extend Hammett s treatment of substituent effects to electrophilic substitutions. It was felt by some that the effects of substituents in electrophilic aromatic substitutions were particularly susceptible to the specific demands of the reagent, and that the variability of the polarizibility effects, or direct resonance interactions, would render impossible any attempted correlation using a two-parameter equation. - o This view was not universally accepted, for Pearson, Baxter and Martin suggested that, by choosing a different model reaction, in which the direct resonance effects of substituents participated, an equation, formally similar to Hammett s equation, might be devised to correlate the rates of electrophilic aromatic and electrophilic side chain reactions. We shall now consider attempts which have been made to do this. 

The occurrence of a hydrogen isotope effect in an electrophilic substitution will certainly render nugatory any attempt to relate the reactivity of the electrophile with the effects of substituents. Such a situation occurs in mercuration in which the large isotope effect = 6) has been attributed to the weakness of the carbon-mercury bond relative to the carbon-hydrogen bond. The following scheme has been formulated for the reaction, and the occurrence of the isotope effect indicates that the magnitudes of A j and are comparable ... 

In addition to benzene and naphthalene derivatives, heteroaromatic compounds such as ferrocene[232, furan, thiophene, selenophene[233,234], and cyclobutadiene iron carbonyl complexpSS] react with alkenes to give vinyl heterocydes. The ease of the reaction of styrene with sub.stituted benzenes to give stilbene derivatives 260 increases in the order benzene < naphthalene < ferrocene < furan. The effect of substituents in this reaction is similar to that in the electrophilic aromatic substitution reactions[236]. 

The amino group activates the thiazole ring toward electrophilic centers. This point is illustrated by the rate constants of the reaction between 2-dialkylaminothiazoles (32) and methyl iodide in nitromethane at 25 C (Scheme 23) (158). The steric effects of substituents on nitrogen are... 

The quatemization reaction of the thiazole nitrogen has been used to evaluate the steric effect of substituents in heterocyclic compounds since thiazole and its alkyl derivatives are good models for such study. In fact, substituents in the 2- and 4-positions of the ring only interact through their steric effects (inductive and resonance effects were constant in the studied series). The thiazole ring is planar, and the geometries of the ground and transition states are identical. Finally, the 2- and 4-positions have been shown to be different (259. 260). 

The transmission of the effects of substituents in the 2- and 4-positions across the thiazole ring has been determined from the rates of solvolysis... 

Alkenes resemble alkanes m most of their physical properties The lower molecular weight alkenes through 4 are gases at room temperature and atmospheric pressure The dipole moments of most alkenes are quite small Among the 4 isomers 1 butene cis 2 butene and 2 methylpropene have dipole moments m the 0 3-05 D range trans 2 butene has no dipole moment Nevertheless we can learn some things about alkenes by looking at the effect of substituents on dipole moments... 

Table 6 3 shows that the effect of substituents on the rate of addition of bromine to alkenes is substantial and consistent with a rate determining step m which electrons flow from the alkene to the halogen Alkyl groups on the carbon-carbon double bond release electrons stabilize the transition state for bromonium ion formation and increase the reaction rate... 

Often the directing effects of substituents reinforce each other Brommation of p mtrotoluene for example takes place at the position that is ortho to the ortho para directing methyl group and meta to the meta directing nitro group... 

Because the position of electrophilic attack on an aromatic nng is controlled by the direct ing effects of substituents already present the preparation of disubstituted aromatic com pounds requires that careful thought be given to the order of introduction of the two groups Compare the independent preparations of m bromoacetophenone and p bromoace tophenone from benzene Both syntheses require a Friedel-Crafts acylation step and a bromination step but the major product is determined by the order m which the two steps are carried out When the meta directing acetyl group is introduced first the final product IS m bromoacetophenone... 

Deactivating substituent (Sections 12 11 and 12 13) A group that when present in place of hydrogen causes a particular reaction to occur more slowly The term is most often ap plied to the effect of substituents on the rate of electrophilic aromatic substitution... 

Table 7.51 Effect of Substituent Groups on Alkyl Chemical Shifts 7.102...

Disubstituted Boranes. Even slight differences in stetic or electronic effects of substituents may have an effect on the hydroboration reaction course. These effects are well demonstrated in disubstituted boranes, and consequentiy a range of synthetically useful reagents has been developed. 

Other examples illustrating the effect of substituent distribution on properties include (/) enzymatic stabiUty of hydroxyethjlceUulose (16,17) (2) salt compatibihty of carboxymethylceUulose (18,19) and (J) thermal gelation properties of methylceUulose (20). The enzymatic stabUity of hydroxyethylceUulose is an example where the actual position of the substituents within the anhydroglucose units is considered important. Increasing substitution at the C2 position promotes better resistance toward enzymatic cleavage of the polymer chain. Positional distribution is also a factor in the other two examples. 

The shade may be varied by choosing amines. For aromatic amines, the steric effect of substituents in the ortho position reduces the conjugation of the anibno group with the anthraquinone moiety, and the result is a hypsochromic shift and brighter shade. Thus Cl Acid Blue 129 (120) has a more reddish and brighter shade than Cl Acid Blue 25 (118). Cycloalkylamines have a similat effect on the shade. Cl Acid Blue 62 [5617-28-7] (125) Cl 62045) is an example. 

---