Steric effects Subject

Hydrolysis reactions involving tetrahedral intermediates are subject to steric and electronic effects. Electron-withdrawing substituents faciUtate, but electron-donating and bulky substituents retard basic hydrolysis. Steric effects in acid-cataly2ed hydrolysis are similar to those in base-cataly2ed hydrolysis, but electronic effects are much less important in acid-cataly2ed reactions. Higher temperatures also accelerate the reaction. 

Ionization reaction rates are subject to both electronic and steric effects. The most important electronic effects are stabilization of the carbocation by electron-releasing... 

A few comments on the polar effects of the substituents reported in Tables IX—XI are now relevant. With the exception of 4-chloro-5-nitroquinoline (see Section IV, C, l,c), they involve only positions not subject to primary steric effects. The relations to the reaction center are of the conjugative cata, amphi) as well as of the non-conjugative class meta, epi, pros) as shown in Chart 3 by structures 45 and 46. 

The scope of heteroaryne or elimination-addition type of substitution in aromatic azines seems likely to be limited by its requirement for a relatively unactivated leaving group, for an adjacent ionizable substituent or hydrogen atom, and for a very strong base. However, reaction via the heteroaryne mechanism may occur more frequently than is presently appreciated. For example, it has been recently shown that in the reaction of 4-chloropyridine with lithium piperidide, at least a small amount of aryne substitution accompanies direct displacement. The ratio of 4- to 3-substitution was 996 4 and, therefore, there was 0.8% or more pyridyne participation. Heteroarynes are undoubtedly subject to orientation and steric effects which frequently lead to the overwhelming predominance of... 

The approach taken above estimates the effect of the metal by simply considering its electrostatic effect (subjected, of course, to the correct steric constraint as dictated by the metal van der Waals parameters). To examine the validity of this approach for other systems let s consider the reaction of the enzyme carbonic anhydrase, whose active site is shown in Fig. 8.6. The reaction of this enzyme involves the hydration of C02, which can be described as (Ref. 5)... 

Since steric effects can change catalysis (e.g., the above mentione trypsin case), one may still argue that such effects do influence the correl tion between structure and function. However, this case is not so relevant t structure-function correlation since the steric effects establish new structui and the activity associated with this structure is the main subject of ot... 

The steric environment of the atoms in the vicinity of the reaction centre will change in the course of a chemical reaction, and consequently the potential energy due to non-bonded interactions will in general also change and contribute to the free energy of activation. The effect is mainly on the vibrational energy levels, and since they are usually widely spaced, the contribution is to the enthalpy rather than the entropy. When low vibrational frequencies or internal rotations are involved, however, effects on entropy might of course also be expected. In any case, the rather universal non-bonded effects will affect the rates of essentially all chemical reactions, and not only the rates of reactions that are subject to obvious steric effects in the classical sense. 

Similarly to peroxycarboxylic acids, DMDO is subject to cis or syn stereoselectivity by hydroxy and other hydrogen-bonding functional groups.93 However a study of several substituted cyclohexenes in CH3CN —H20 suggested a dominance by steric effects. In particular, the hydroxy groups in cyclohex-2-enol and... 

The addition of trialkylsilyl radicals to 1,2-disubstituted ethylene derivatives is subject to a steric effect [49], This shows itself in the greater Ee0 value for Et3Si addition to RCH=CHR compared with that for the addition of the same radical to CH2=CHR. The contribution of... 

Although alkylidenecarbenes (R)2C=C and carbenoids 22-24 have an ip-hybridized carbene center similar to that of vinylidenecarbenes, the reactivity will be subject to the steric influence of substituents R3 and R4 because its location is closer to the carbene center than vinylidenecarbenes (Scheme 11). The steric effect was exerted in the reactions of 2-methylpropenylidene 22 generated from 2-methyl-1-chloropropene and butyllithium (BuLi) (Scheme ll).22 23 The results are summarized in Table 5. A more detailed discussion on the stereoselectivity of this reaction will be revisited in Section HI. A. 

Bimolecular reactions of aniline with /V-acyloxy-/V-alkoxyamides are model Sn2 processes in which reactivity is dictated by a transition state that resembles normal Sn2 processes at carbon. Electronic influences of substituents support a non-synchronous process which has strong charge separation at the transition state and which is subject to steric effects around the reactive centre, at the nucleophile but not on the leaving group. The sp3 character of nitrogen and disconnection between the amino group and the amide carbonyl renders these reactions analogous to the displacement of halides in a-haloketones. 

In summary, we expect that 2,3-substitution will not greatly alter the conformational preference of the diene system, L e. conformational isomerism of 2,3-difluoro-butadiene will be subject to the same electronic factors as that of the unsubstituted diene and these factors operate in the same direction in both cases. It is expected that, by analogy to 1,3-butadiene, the order of conformer stability of 2,3-difluoro-butadiene will be dictated by steric effects, L e. it will be tram > gauche > cis. 

Steric effects were also found to be important for determining the reactivity of rhodium complexes containing N-heterocyclic carbene (NF1C) ligands [47] (Scheme 10), which have been the subject of intense in-... 

The results suggest that the five-membered peptide chelate ring, in which the atoms are nearly coplanar, may be more subject to steric effects than is the case for the gauche conformation of chelate rings of ethylenediamine and its C-methyl derivatives. However, the corresponding nucleophilic displacement reactions have not been studied and it is too early to draw... 

However, given a sufficiently strong steric effect, a permanent twist can be induced in a carbon-carbon double bond even without a push-pull effect. This is a field that has been the subject of much interest, as exemplified by the intense but still unsuccessful search for tetra-/m-butylethylene, and by the still very active studies of trans-cyclooctenes. Besides the synthetic challenge, such compounds present interesting chiroptical and other physical properties, and a knowledge of their heats of formation presents crucial tests for current force fields. 

Reactivity ratios for all the combinations of butadiene, styrene, Tetralin, and cumene give consistent sets of reactivities for these hydrocarbons in the approximate ratios 30 14 5.5 1 at 50°C. These ratios are nearly independent of the alkyl-peroxy radical involved. Co-oxidations of Tetralin-Decalin mixtures show that steric effects can affect relative reactivities of hydrocarbons by a factor up to 2. Polar effects of similar magnitude may arise when hydrocarbons are cooxidized with other organic compounds. Many of the previously published reactivity ratios appear to be subject to considerable experimental errors. Large abnormalities in oxidation rates of hydrocarbon mixtures are expected with only a few hydrocarbons in which reaction is confined to tertiary carbon-hydrogen bonds. Several measures of relative reactivities of hydrocarbons in oxidations are compared. 

It should be noted that the last reaction is anomalous owing to the soft nature of the selenium such that the intermediate is an episelenonium species (i.e. less carbocat-ionic) and the attack of the counterion is subject to steric effects such as the 2,6-endo interaction. 

Of this list, hb interactions can be sensitive to steric effects. This has been established for amino acid transport parameters such as the hydrophobicities and partition coefficients. There is some evidence that charge transfer interactions are also subject to steric effects. 

Of the remaining interactions, those which involve the dipole moment of the bas may be subject to an indirect steric effect as the preferred conformation of the bas may depend on steric effects and the dipole moment will depend on the conformation. 

The Id and Ii interactions may be subject to steric effects resulting from steric hindrance to the solvation of the group which ionizes with the nature of the substituent. 

The variation in the add-catalyzed hydrolysis of aliphatic carboxylic esters RCOOEt is mostly subject to the steric effect intramolecularly exerted by the substituent R on the formation of the tetrahedral reaction intermediate. Taft4) defined the steric parameter E, as Eq. 3,... 

Reduction of aldehydes and ketones. Earlier work on amine borane reagents was conducted mainly with tertiary amines and led to the conclusion that these borane complexes reduced carbonyl compounds very slowly, at least under neutral conditions, and that the yield of alcohols is low. Actually complexes of borane with primary amines, NHj or (CH3)3CNH2, reduce carbonyl compounds rapidly and with utilization of the three hydride equivalents. BH3 NH3 is less subject to steric effects than traditional complex hydrides. A particular advantage is that NH3 BH3 and (CH3)3CNH2 BH3 reduce aldehyde groups much more rapidly than keto groups, but cyclohexanone can be reduced selectively in the presence of aliphatic and aromatic acyclic ketones. 

B Uoster 7 has pointed out the parallelism of the aldol and Darkens reactions -with respect to electronic effects. It is conceivable that steric effects can also play an important role in the reactivity of the carbonyl component, but there is insufficient evidence in the literature at present to warrant any definitive conclusion on this subject.183 ... 

Where (H20) is the first order rate constant for the uncatalyzed reaction at a given water concentration, k3 = A2/[H20], A2 = Ac/[C1 ], kc = ki (catalyzed) + kx (uncatalyzed), and [Cl-] is the concentration of chloride ion from neutral salts. They again oppose the Swain mechanism on the basis a) that the unimolecular dissociation of the pentacovalent complex should be subject to electrophylic catalysis, b) that the steric effects are too great, c) that symmetrical chloride exchange is... 

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