Steric and Inductive Effects

The alkyl and alkoxy substituents of phosphate or phosphonate esters also affect the phosphorylating abiUty of the compound through steric and inductive effects. A satisfactory correlation has been developed between the quantitative measure of these effects, Tafts s O, and anticholinesterase activity as well as toxicity (33). Thus long-chain and highly branched alkyl and alkoxy groups attached to phosphoms promote high stabiUty and low biological activity. 

Steric and inductive effects determine the rate of formation of the pentacovalent siUcon reaction complex. In alkaline hydrolysis, replacement of a hydrogen by alkyl groups, which have lower electronegativity and greater steric requirements, leads to slower hydrolysis rates. Replacement of alkyl groups with bulkier alkyl substituents has the same effect. Reaction rates decrease according to ... 

In a study of the steric and inductive effects of the alkyl group on the rate of hydrolysis of alkyltrialkoxysilanes, it was also shown [11] that the alkyl substituent on silicon had a significant effect on the rates of hydrolysis under basic and acidic conditions in aqueous medium. 

A method of preparing either cis- or trans-aziridine carboxylates (39) from A-diphenylphosphinylimines (37) and the chiral enolate (36) derived from A-bromo-acetyl 25-2,10-camphorsultam (35) has been reported.54 When the arylimine is substituted in the ortho -position, the product is either a mixture of cis- and trans-aziridine or only the trans-isomer. When the ortho-substituent is H or NO2, only a cz s-aziridine is obtained. The suggested mechanism is partially shown in Scheme 18. Both steric and inductive effects of the ortho- substituent affect the stereochemistry of the addition complex (38) and the stereochemistry of the final aziridine. 

The equilibrium in these reactions may favor the products or the reactants, depending on the strength of the nucleophile and the structure of the carbonyl compound. Stronger nucleophiles shift the equilibrium toward the products, and very strong nucleophiles give an irreversible reaction, that is, one that proceeds in only one direction, from the reactants to the products. The structure of the aldehyde or ketone exerts its influence through resonance, steric, and inductive effects, as usual. It is easiest to see these effects in examples, so let us proceed to examine some of the nucleophiles that can be used in these addition reactions. 

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. 

A third factor regulating the speed of lipolysis is the hydrophobicity of the ester. The normal substrates of lipase—the natural triglycerides— are insoluble in water, and the enzyme acts at the oil-water interface. Thus, lipases have been defined as esterases that act on insoluble substrates at such interfaces. However, triglycerides that are similar in steric and inductive effects may still react with different velocities even if all reactions take place at oil-water interfaces. For instance, emulsified tributyrin is hydrolyzed 20 times faster than emulsified triacetin. This difference is caused by the different hydrophobicity of the triglycerides not by the different chain lengths of butyric and acetic acid. 

Reaction kinetics steric and inductive effects by H bonds. 

Assuming that resonance, steric and inductive effects are additive, an inductive polar substituent constant (qj) may be defined by employing standard reactions reasonably assumed to possess no resonance transmission or steric effect. 

The reaction of NO3 with unsaturated ethers proceeds by addition to the >C=C< double bond. Both steric and inductive effects are known to influence the reactivity of NO3 with unsaturated alcohols, e.g. 2-methyl-3-butene-2-ol is slightly less reactive than 1-butene. Unsaturated ethers are more reactive than unsaturated alcohols towards NO3. Comparison of the measured rate constants shows that, similar to the reaction with O3, the presence of the carbonyl group decreases the reactivity of NO3 toward the >C=C< double bond. The reaction of NO3 with unsaturated oxygenates proceeds by addition to either one of the carbon atoms of >C=C< double bond, preferentially to the most substituted radical. In the presence of NOx, the reaction may ultimately lead to organic nitrates among the first generation products. 

Chlorine and bromine with inductive electron withdrawal ( —I) > mesomeric electron donation (-I- M) direct boron to the a position, the degree of selectivity varying with structure " . The direction of addition to allylic derivatives is influenced by steric and inductive effects of the substituent . Electron-withdrawing groups direct the boron... 

Kinetic measurements on the dimeric hexamethoxydisiloxane species generated values of a = 0.0007 L/mol-min and kw = 0.0011 L/mol-min, versus 0.001 and 0.006 L/mol-min for the monomer (46). The alcohol-producing condensation reaction is about the same for monomers and dimers, but the water-producing condensation is significantly lower for dimers. This difference is probably due to both increased steric crowding in the dimer and the inductive effect of an -OSi ligand retarding the reaction, as described earlier. Steric and inductive effects are important variables on reaction kinetics. 

Such high sensitivity of amino radical cations to steric and inductive effects was also observed in hydrogen abstraction processes from saturated hydrocarbons 31,32) ... 

T.P.G. Sutter, R. Rahimi, P. Hambright, J.C. Bommer, M. Kumar, and P. Neta, Steric and Inductive Effects on the Basicity of Porphyrins and on the Site of Protonation of Porphyrin Dianions Radiolytic Reduction of Porphyrins and Metalloporphyrins to Chlorins or Phlorins, J. Chem. Soc. Faraday Trans., 89 (1993) 495. 

Additional to the polar factors, the steric requirements of the alkyl substituents may play a dominating role by hindering approach of the base to a beta proton or alternatively causing a divergence from the requisite coplanarity of reacting bonds in the transition state for elimination. Often, along a series of alkyl substituents, both steric and inductive effects vary in the same direction and the interpretation of the salient orientating features is a matter of personal preference. 

Relative reaction rates of hydrolysis, condensation, reesterification, and dissolution must be understood and controlled to dictate structural evolution. However, accurate values for rate constants are difficult to obtain because of the enormous number of distinguishable reactions as next nearest neighbors are considered, and to the concurrency of these reactions. Assink and Kay [45] use a simplified statistical model assuming that the local silicon environment does not affect reaction rates, and the reactions for a particular silicon species are the product of a statistical factor and rate constant. These assumptions ignore steric and inductive effects. For example, this model predicts that the relative rate constants for the four sequential hydrolysis steps leading from TMOS to Si(OH)4 would be 4 3 2 1. This model was applied to acid-catalyzed TMOS sols with W values ranging from 0.5 to 2.0. Si NMR spectra on the temporal evolution of various silicon species show the model is in excellent agreement with experimental results. A lower limit for fen was calculated as 0.2 L/mol-min. Values for few and feA are 0.006 and 0.001 L/mol-min, respectively. 

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