Reactivity steric effects

R. Brooks [42-44] the process of electron transfer for K to oriented t-butyl bromide is found strongly dependent on the orientation. Systems involving metal atoms are traditional favorites of molecular beam studies, particularly of stereodynamics. In recent experiments [45], with brute force oriented ICl, experimental determination was made of the cone of acceptance for reactivity (steric effect) in a "harpooning" reaction, Sr + ICl leading to electroiucally excited products detected via their chemiluminescence... 

The chemical structures of the monomers also determine their reactivity toward cationic polymerizations. Electron-donating groups enhance the electron densities of the double bonds. Because the monomers must act as nucleophiles or as electron donors in the course of propagation, increased electron densities at the double bonds increase the reaction rates. It follows, therefore, that electron-withdrawing substituents on olefins will hinder cationic polymerizations. They will, instead, enhance the ability for anionic polymerization. The polarity of the substituents, however, is not the only determining factor in monomer reactivity. Steric effects can also exert considerable controls over the rates of propagation and the modes of addition to the active centers. Polymerizations... 

The equation does not take into account such pertubation factors as steric effects, solvent effects, and ion-pair formation. These factors, however, may be neglected when experiments are carried out in the same solvent at the same temperature and concentration for an homogeneous set of substrates. So, for a given ambident nucleophile the rate ratio kj/kj will depend on A and B, which vary with (a) the attacked electrophilic center, (b) the solvent, and (c) the counterpart cationic species of the anion. The important point in this kind of study is to change only one parameter at a time. This simple rule has not always been followed, and little systematic work has been done in this field (12) stiH widely open after the discovery of the role played by single electron transfer mechanism in ambident reactivity (1689). 

If the medium is sufficiently basic to generate the arabident anion 31. mixtures of products resulting from N-nng and N-exocyclic reactivity are observed. Here again steric effects can preferentially orient the whole reaction toward one of the two nitrogens. A general study clearly delineating the rules of behavior for 31 accordine to the nature of R. the... 

The reaction of 2.4-dimethylthiazole with butyllithium shows that, in contrast to 2-methylthiazole, the benzyl position (the 2-position) is the most reactive. The effect of the substituent in the 4-position may well be steric 4-r-butyl-2-methylthiazole in the same reaction gives no 5-substituted product (223). 

Reactions such as catalytic hydrogenation that take place at the less hindered side of a reactant are common m organic chemistry and are examples of steric effects on reactivity Previously we saw steric effects on structure and stability m the case of CIS and trans stereoisomers and m the preference for equatorial substituents on cyclo hexane rings... 

This last identification makes the Q s strictly a matter of resonance, whereas the general concept of reactivity also includes steric effects. The effects... 

The reactivity of the individual O—P insecticides is determined by the magnitude of the electrophilic character of the phosphoms atom, the strength of the bond P—X, and the steric effects of the substituents. The electrophilic nature of the central P atom is determined by the relative positions of the shared electron pairs, between atoms bonded to phosphoms, and is a function of the relative electronegativities of the two atoms in each bond (P, 2.1 O, 3.5 S, 2.5 N, 3.0 and C, 2.5). Therefore, it is clear that in phosphate esters (P=0) the phosphoms is much more electrophilic and these are more reactive than phosphorothioate esters (P=S). The latter generally are so stable as to be relatively unreactive with AChE. They owe their biological activity to m vivo oxidation by a microsomal oxidase, a reaction that takes place in insect gut and fat body tissues and in the mammalian Hver. A typical example is the oxidation of parathion (61) to paraoxon [311-45-5] (110). 

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. 

Resonance effects are the primary influence on orientation and reactivity in electrophilic substitution. The common activating groups in electrophilic aromatic substitution, in approximate order of decreasing effectiveness, are —NR2, —NHR, —NH2, —OH, —OR, —NO, —NHCOR, —OCOR, alkyls, —F, —Cl, —Br, —1, aryls, —CH2COOH, and —CH=CH—COOH. Activating groups are ortho- and para-directing. Mixtures of ortho- and para-isomers are frequently produced the exact proportions are usually a function of steric effects and reaction conditions. 

Because of steric effects, TMXDI is less reactive than the trifunctional derivatives of hexamethylene diisocyanate (HDI) (1,6-diisocyanatohexane)... 

Examples of effects of reactant stmcture on the rate of nucleophilic substitution reactions have appeared in the preceding sections of this chapter. The general trends of reactivity of primaiy, secondary, and tertiaiy systems and the special reactivity of allylic and benzylic systems have been discussed in other contexts. This section will emphasize the role that steric effects can pl in nucleophilic substitution reactions. 

We will discuss shortly the most important structure-reactivity features of the E2, El, and Elcb mechanisms. The variable transition state theoiy allows discussion of reactions proceeding through transition states of intermediate character in terms of the limiting mechanistic types. The most important structural features to be considered in such a discussion are (1) the nature of the leaving group, (2) the nature of the base, (3) electronic and steric effects of substituents in the reactant molecule, and (4) solvent effects. 

Reductions by NaBKt are characterized by low enthalpies of activation (8-13kcal/mol) and large negative entropies of activation (—28 to —40eu). Aldehydes are substantially more reactive than ketones, as can be seen by comparison of the rate data for benzaldehyde and acetophenone. This relative reactivity is characteristic of nearly all carbonyl addition reactions. The reduced reactivity of ketones is attributed primarily to steric effects. Not only does the additional substituent increase the steric restrictions to approach of the nucleophile, but it also causes larger steric interaction in the tetrahedral product as the hybridization changes from trigonal to tetrahedral. 

When this stereoelectronic requirement is combined with a calculation of the steric and angle strain imposed on the transition state, as determined by MM-type calculations, preferences for the exo versus endo modes of cyclization are predicted to be as summarized in Table 12.3. The observed results show the expected qualitative trend. The observed preferences for ring formation are 5 > 6, 6 > 7, and 8 > 7, in agreement with the calculated preferences. The relationship only holds for terminal double bonds. An additional alkyl substituent at either end of the double bond reduces the relative reactivity as a result of a steric effect. 

Taft began the LFER attack on steric effects as part of his separation of electronic and steric effects in aliphatic compounds, which is discussed in Section 7.3. For our present purposes we abstract from that treatment the portion relevant to aromatic substrates. Hammett p values for alkaline ester hydrolysis are in the range +2.2 to +2.8, whereas for acid ester hydrolysis p is close to zero (see Table 7-2). Taft, therefore, concluded that electronic effects of substituents are much greater in the alkaline than in the acid series and. in fact, that they are negligible in the acid series. This left the steric effect alone controlling relative reactivity in the acid series. A steric substituent constant was defined [by analogy with the definition of cr in Eq. (7-22)] by Eq. (7-43), where k is the rate constant for acid-catalyzed hydrolysis of an orr/to-substituted benzoate ester and k is the corresponding rate constant for the on/to-methyl ester note that CH3, not H, is the reference substituent. ... 

The steric constant Es and related quantities do not constitute the only approach to the study of steric effects on reactivity. Steric strain energy calculations and topological indices are more recent approaches. Qualitative concepts have been... 

Hydrolysis of an enamine yields a carbonyl compound and a secondary amine. Only a few rate constants are mentioned in the literature. The rate of hydrolysis of l-(jS-styryl)piperidine and l-(l-hexenyl)piperidine have been determined in 95% ethanol at 20°C 13). The values for the first-order rate constants are 4 x 10 sec and approximately 10 sec , respectively. Apart from steric effects the difference in rate may be interpreted in terms of resonance stabilization by the phenyl group on the vinyl amine structure, thus lowering the nucleophilic reactivity of the /3-carbon atom of that enamine. 

The rate of saponification of ethyl 2-thenoate, in contrast to ethyl 3-thenoate, was found to be considerably slower than predicted from the pKa of the acid, showing that the reactivities of thiophenes do not parallel those of benzene. The first explanation, that this was produced by a steric effect of the ring sulfur similar to the case in or /lo-substituted benzenes and in ethyl 1-naphthoate, could not be upheld when the same effect was found in ethyl 2-furoate. It was later ascribed to a stereospecific acid strengthening factor, involving the proper relation of the carboxylic hydrogen and the heteroatom, as the rate of saponification of 2-thienylacrylic acid was in agreement with that predicted from the acid constants. ... 

Secondary steric effects of nitro groups are more easily detected by comparing the reactivities with those of aza derivatives. For example, in structure 20 the rate depression on passing from methyl to -butyl is only 2.5-fold and can be attributed to an inductive effect, whereas in structure 21 a similar change involves the factor 16, which can be attributed in part to steric inhibition of resonance (S.I.R.) of thep-N02 group (reaction with piperidine). 

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