Effect of Substrate Structure

Nucleophilicity and basicity parallel each other only when there are no steric effects, and the species compared are within the same row of the periodic table. 

Heavier atoms tend to be more nucleophilic because they are more poiarizable thus, RS is more nucleophilic than RO . 

In HSAB theory, hard electrophilic centers such as protons and carbonyi groups respond best to hard bases such as hydroxyi ion. Soft, poiarizabie centers such as Mei or Brj respond best to soft nucleophiies such as RS and aikenes. 

Good leaving groups are the anions of strong acids. 

Rank the following three reactions in order of the rate at which you expect they will proceed  

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The effect of substrate structure on product profile is further illustrated by the reactions of cis- and trons-stilbene oxides 79 and 83 with lithium diethylamide (Scheme 5.17) [32]. Lithiated cis-stilbene oxide 80 rearranges to enolate 81, which gives ketone 82 after protic workup, whereas with lithiated trans-stilbene oxide 84, phenyl group migration results in enolate 85 and hence aldehyde 86 on workup. Triphenylethylene oxide 87 underwent efficient isomerization to ketone 90 [32]. 

In the discussion of electrophilic aromatic substitution (Chapter 11) equal attention was paid to the effect of substrate structure on reactivity (activation or deactivation) and on orientation. The question of orientation was important because in a typical substitution there are four or five hydrogens that could serve as leaving groups. This type of question is much less important for aromatic nucleophilic substitution, since in most cases there is only one potential leaving group in a molecule. Therefore attention is largely focused on the reactivity of one molecule compared with another and not on the comparison of the reactivity of different positions within the same molecule. 

Anthonsen, T. and Hoff, B. (1998) Resolution of derivatives of 1,2-propanediol with lipase B from C antarctica. Effect of substrate structure, medium, water activity and acyl donor on enantiomeric ratio. Chem. Phys. Lipids, 93, 199-207. 

Boger and co-workers performed a detailed study on the effect of substrate structural features on the 17-membered ring macrolactamization. It was found that the substituent at the remote C4 aryl position had a profound effect on the rate and yield of the cyclization. Substrates bearing either a free phenol or no substituent were found to cyclize more efficiently, whereas those bearing methyl or benzyl ethers cyclized considerably less efficiently (Table 1)J5 ... 

The effect of substrate structure on enantioselectivity has been explored for the catalytic intramolecular cyclopropanation reaction of a-diazo-/3-keto arylsulfones.56 It has especially been shown that substitution of the phenyl ring by a methyl at the ortho position of the sulfonyl group dramatically increased the ees, with values up to 93%. 

V. T. Pham and R. S. Phillips, Effects of substrate structure and temperature on the stereospedfidty of secondary alcohol dehydrogenase from Thermoanaerobacter ethanolicus,]. Am. Chem. Soc. 1990, 112, 3629-3632. 

In analogy to the discussion of the loading step processes, both the processes occurring in the curing step and the effect of substrate structure on these processes will be discussed. Whereas the study of the loading step processes involved analysis of the solvent, here the modified substrate is studied. For this, various spectroscopic techniques are applied. The discussion is focused on the silicon side of the aminosilane molecule. The interactions at the amine side will be discussed in the next paragraph. 

In analogy to the loading step study, the effect of substrate structure has been studied by modifying mesoporous silica gels with a variable mean pore diameter.28 Sample pretreatment and curing (20 h, 423 K) were performed under vacuum. Variation of the pretreatment temperature causes a change in specific surface area and silanol number. 

Effect of Substrate Structure in the Hydrogenation of a-Keto Acetals22... 

The determination of binding constants, K, and inhibitor constants, Ki, for micelle-catalyzed reactions permits at least qualitative interpretations of the effect of substrate structure on the extent and nature of micellar complexation and allows a comparison of the magnitude of the binding constants for substrates in micellar systems with those in enzymatic systems. The hmited quantity of such data available at... 

Table 2 Effect of Substrate Structure on the Competition Between Dimerization and Hydrogenation in the Reduction of Ring-Substituted Allylbenzenes (4) ...

In view of the complications imposed on interpretation of kinetic isotope effects by quantum mechanical tunnelling and a variable profile of isotope effect with proton transfer to different bases, a more certain prediction would seem most probable if comparisons are restricted to reactions of a series of similar substrates within a given reaction medium. Within this framework it is possible to make reasonable predictions of the effect of substrate structure on the nature of the transition state for elimination using only primary kinetic hydrogen isotope effects. 

The first-order kinetics, lack of dependence of rate upon pressure in the gas phase above 1 torr, absence of catalysis, and stereospecificity all show that vinyl allyl ether isomerizations are unimolecular reactions. The effects of substrate structure and solvents on reactivity indicate that the rate-limiting transition state does not resemble an ion pair. Methyl substituents on the a and y carbons of the allylic group increase reactivity by only about 10- and 2.5-fold respectively, which is very much less than substituent effects on ionic allylic reactions. While the isomerization of vinyl a-methylallyl ether is about ten times faster in organic solvents than in the vapor phase, the solvent effect is small and does not correlate with solvent polarity. 

The effect of substrate structure on diffusion, since most work has been done with gel model systems, but real systems are likely to be more complex... 

Examples of effects of substrate structure on the rates of nucleophilic substitution reactions have appeared in the preceding sections of this chapter. Additionally, some special effects will be covered in detail in succeeding sections. This section will emphasize the role steric effects can play in nucleophilic substitution reactions. 

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