Steric and Solvent Effects in Substitution

The a value measures the intrinsic reactivity of the complex, and measures how much the rate is affected by the or-donor strength of the ligand. The result is a Hammett-type linear free eneigy (LFE) relationship. Very bulky ligands show rates slower than predicted, however. 

As we have seen in the last few sections, solvents can act as ligands. Of the common solvents, the ones most likely to bind, and therefore perha to divert the reaction from its intended goal are MeCN, pyridine, MeiSO (dimethylsulfoxide, DMSO), and MC2NCHO (dimethylfoimami, DMF). Several species dissolve cmly in such solvents, which bind to the metal. DMF binds via the carbonyl because the nitrogen lone pair is tied up by resonance with the CO to give  

DMSO is a particularly interesting ligand because it can bind either via the S or the O. Both steric and hard and soft considerations seem to play a role in the choice. Unhindered, soft Rh(I) gives S-bound [Rh(SOMe2)3Cl], for example. CS2 is another solvent that finds restricted use in oiganmnetallic chemistry because it reacts with most complexes SO2 has been used successfully, especially as a low-temperature NMR solvent. 

Arenes can in principle bind to metals, but the reaction is usually either sufficiently slow or thermodynamically unfavorable to permit the satisfactory use of arenes as solvents without significant interference. Alkanes are normally reliably noncoordinating (but see Section 12.4). Many complexes do not have sufficient solubility in the usual alkanes, but solvents such as ethylcyclohexane—the molecules of which pack poorly, leaving gaps in the liquid structure—are significantly belter. IR spectra are best recorded in alkanes because they interact least with the solute and give the sharpest absorbtion peaks. 

Even xenon is able to act as a ligand, as in Seidel and Seppelt s fAu(Xe)4][Sb2FiiJ2, which is even stable enough for an X-ray structural study.  

As we saw in Section 4.4, the substitution rate for an associative reaction changes as we change the incoming ligand L, but what properties of L are important in deciding the rate At first sight this looks complicated because 

Tetrahydrofuran (THF), acetone, water, and ethanol are much less strongly ligating and are widely used. Early transition metal complexes can be very sensitive to solvents containing labile protons, but this depends on the case. All of these solvents can act as weak ligands, and their complexes can be synthetically useful. Ketones usually bind in the mode via O, as in 4.22, but can also bind in the V mode via both C and O, as in 4.23 (Eq. 4.S9). The latter is favored by low steric hindrance and by a strongly back-donating 

In the case of ionic complexes, the choice of counterion may be important, because they may bind to the metal. Several anions in common use are 

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Recent observations bearing on reactivity have usually been scattered and of uneven quality. We can add very few kinetic data on additions (equation 1) to those of a previous review on the other hand, kinetic data for substitutions (equation 2) are available. Studies of substituent, steric and solvent effects, which influence nucleo-philicity and electrophilicity orders as well as stereoselectivity, are limited and usually qualitative. For these reasons, we shall treat some of the large issues in this section and pick others up later in the context of specific nucleophiles. 

One of the main goals in physical organic chemistry is the systematic description of the influence of chemical substitution in the reactivity pattern of molecules.124 The major difficulty to achieve this objective is that substituent effects are experimentally assessed as global responses, and therefore steric and solvent effects may mask the intrinsic electronic contributions. Many detailed linear relationships between substituent groups and chemical properties have been developed to date.71014125 In many cases, such relationships can be expressed quantitatively, thereby providing useful clues for interpreting reaction mechanisms and to predict reaction rates and equilibria. 

The same conclusion was reached in a kinetic study of solvent effects in reactions of benzenediazonium tetrafluoroborate with substituted phenols. As expected due to the difference in solvation, the effects of para substituents are smaller in protic than in dipolar aprotic solvents. Alkyl substitution of phenol in the 2-position was found to increase the coupling rate, again as would be expected for electron-releasing substituents. However, this rate increase was larger in protic than in dipolar aprotic solvents, since in the former case the anion solvation is much stronger to begin with, and therefore steric hindrance to solvation will have a larger effect (Hashida et al., 1975 c). 

The system aminophosphorane (116)-phosphazene (116a) (Scheme 29) studied by Sanchez et al,191 was found to behave differently only 116a can be detected by NMR, i.e. there is no equilibrium. Exactly the opposite situation was found with the system 117-118, in which the only observable species was the aminophosphorane 117. Evidently, the increase in thermodynamic stability results from the formation of a spirophosphorane structure. Similar conclusions were reached by Gololobov et al.191 in the course of a study of structures similar to that of 117. More recently, Stegmann et al.193 extended the scope of their research to substituted 1,2-aryldiamines in a study of the equilibria 119 119a and 120 120a. The thermodynamic parameters AH, AG and AS were determined by NMR. Here too, the position of the equilibrium was found to depend on the substituents (steric and electronic effects), on the solvent and on the temperature. 

Abstract—A review of the literature is presented for the hydrolysis of alkoxysilane esters and for the condensation of silanols in solution or with surfaces. Studies using mono-, di-, and trifunctional silane esters and silanols with different alkyl substituents are used to discuss the steric and electronic effects of alkyl substitution on the reaction rates and kinetics. The influences of acids, bases, pH, solvent, and temperature on the reaction kinetics are examined. Using these rate data. Taft equations and Brensied plots are constructed and then used to discuss the mechanisms for acid and base-catalyzed hydrolysis of silane esters and condensation of silanols. Practical implications for using organofunctional silane esters and silanols in industrial applications are presented. 

The kinetics of polycondensation hy nucleophilic aromatic substitution in highly polar solvents and solvent mixtures to yield linear, high molecular weight aromatic polyethers were measured. The basic reaction studied was between a di-phenoxide salt and a dihaloaromatic compound. The role of steric and inductive effects was elucidated on the basis of the kinetics determined for model compounds. The polymerization rate of the dipotassium salt of various bis-phenols with 4,4 -dichlorodiphenylsulfone in methyl sulfoxide solvent follows second-order kinetics. The rate constant at the monomer stage was found to be greater than the rate constant at the dimer and subsequent polymerization stages. 

In the case of a sterically hindered allylic methoxycarbonyl group, the epoxida-tion of substituted cyclohexenes-1,4-dienes occurs on the opposite side. Further studies on the epoxidation of j3,7-unsaturated cyclohexenecarboxylic acids and esters indicate that the steric and polar effects of the COaMe group result mainly in anh -epoxidation while the carboxyl group in inert solvent exerts a syn directing effect. ... 

Much of the discussion which follows is related to Sjf2 reactions and more specifically to bimolecular nucleophilic substitution at a saturated carbon atom, (Ingold, 1953 Bunton, 1963). Many branches of chemistry have profited from the detailed studies made on this deceptively simple reaction (2), which has attracted the attention of physical organic chemists for many years. Especially notable contributions have been made by Hughes and Ingold (Ingold, 1953). These have led to important advances in our understanding of mechanisms, steric effects, polar substituent effects, salt effects and solvent effects. 

Adsorption of the ketone on montmorillonite clay enhances the axial attack of NaBH reduction to >99% for 4-t-butylcyclohexanone 3.26 and 78% for 3,3,5-trimethylcyclohexanone 3.29 [SRI], Other hindered substituted borohydrides also give higher levels of equatorial attack [CYl]. From the numerous studies to date, it appears that torsional and steric factors are very often predominant, as illustrated by the reduction of eight-membered cyclic taxane derivatives [SH7]. An interesting solvent effect in the reduction of a sugar derivative has been recently shown. The reduction of a substituted rigid six-membered ketone with DIBAH in CH2CI2 or... 

As in the case of solvent exchange reactions, the rate and mechanism of ligand substitution reactions can be systematically tuned through manipulation of steric and electronic effects. The introduction of a metal-carbon bond on an inert metal... 

A study of several substituted alkenes in methanol developed some generalizations pertaining to the capture of bromonium ions by methanol For both E- and Z-disubstituted alkenes, the addition of both methanol and Br was completely anti stereospecific. The reactions were also completely regioselective, in accordance with Markovnikov s rule, for disubstituted alkenes, but not for mono substituted alkenes. The lack of high regioselectivity of the addition to monosubstituted alkenes can be interpreted as competitive addition of solvent at both the mono- and unsubstituted carbons of the bromonium ion. This competition reflects conflicting steric and electronic effects. Steric factors promote addition of the nucleophile at the unsubstituted position, whereas electronic factors have the opposite effect. 

Nucleophilic substitution reactions are one of the most important classes of reactions in organic chemistry. In particular, 8 2 reactions are among the most extensively stndied chemical processes in solution and in the gas phase, both theoretically and experimentally. The history of the study of these reactions closely parallels (and is sometimes responsible for) the development of concepts such as structure-reactivity relationships, linear free-energy relationships, steric inhibition, kinetics as a probe of mechanism, stereochemistry as a probe of mechanism and solvent effects. 

Equation 4 can be classified as S, , ie, substitution nucleophilic bimolecular (221). The rate of the reaction is influenced by several parameters basicity of the amine, steric effects, reactivity of the alkylating agent, and solvent polarity. The reaction is often carried out in a polar solvent, eg, isopropanol, which may increase the rate of reaction and make handling of the product easier. 

Bromination has been shown not to exhibit a primary kinetic isotope effect in the case of benzene, bromobenzene, toluene, or methoxybenzene. There are several examples of substrates which do show significant isotope effects, including substituted anisoles, JV,iV-dimethylanilines, and 1,3,5-trialkylbenzenes. The observation of isotope effects in highly substituted systems seems to be the result of steric factors that can operate in two ways. There may be resistance to the bromine taking up a position coplanar with adjacent substituents in the aromatization step. This would favor return of the ff-complex to reactants. In addition, the steric bulk of several substituents may hinder solvent or other base from assisting in the proton removal. Either factor would allow deprotonation to become rate-controlling. 

The k term is independent of Y and would, therefore, appear to be dissociative, but it is in fact found to be solvent-dependent and so it is thought to be associative. (It is also found to be sensitive to steric effects in the same manner as the k2 pathway.) A plausible pathway for the k route is slow solvolysis followed by fast substitution... 

In similarly substituted olefins Kf is strongly influenced by steric effects, as shown by the comparison of tetraisobutylethylene with adamantylideneadamantane and (i,/-D3-trishomocubylidene-D3-trishomocubane. In particular, the comparison between cyclohexene and the two tetrasubstituted cage olefins indicates that Kf increases at least by a factor of 103 on passing from a 1,2 disubstituted to a tetrasubstituted olefin. This dependence is likely to be similar in other solvents, because solvent effects on Kf are modest. 

The molecular modelling approach, taking into account the pyruvate—cinchona alkaloid interaction and the steric constraints imposed by the adsorption on the platinum surface, leads to a reasonable explanation for the enantio-differentiation of this system. Although the prediction of the complex formed between the methyl pyruvate and the cinchona modifiers have been made for an ideal case (solvent effects and a quantum description of the interaction with the platinum surface atoms were not considered), this approach proved to be very helpful in the search of new modifiers. The search strategy, which included a systematic reduction of the cinchona alkaloid structure to the essential functional parts and validation of the steric constraints imposed to the interaction complex between modifier and methyl pyruvate by means of molecular modelling, indicated that simple chiral aminoalcohols should be promising substitutes for cinchona alkaloid modifiers. Using the Sharpless symmetric dihydroxylation as a key step, a series of enantiomerically pure 2-hydroxy-2-aryl-ethylamines... 

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