Reaction steric effects

When the halide is bonded to an allylic system (CH CH-CH -X) an alkoxide ion will react analogously to the previously described S 2 displacement on an alkyl halide. The most significant difference is the rate enhancing effect of the alkene moiety which has been attributed to a decrease in the activation energy of the reaction (9). A second possible mode of reaction is available with allylic halides. This mode of displacement is usually called S 2 and, in general, will be promoted relative to the normal displacement when there are substituents on the alpha carbon which tend to inhibit the normal SN2 pathway by inductive or steric effects (Reaction VII). 

Secondary amine acid acceptors can terminate chain growth by reacting with the diadd halide unless amine reactivity is minimized by steric effects. Reactions between a tertiary amine add acceptor and the acid halide or certain solvents must also be avoided. An add chloride and a tertiary amine can react to form a monoamide and an alkyl halide (Equation 13.20). This reaction is known to occur in fair yield at high temperatures and probably takes place to some extent at room temperature [67-69]. In the usual preparative method wherein diacid halide is added to a solution of diamine and a strongly basic acid acceptor, no difficulty is experienced if the polycondensation reaction is rapid. As the polycondensation reaction rate decreases, the potential for interference by side reactions increases. In a polymerization system, this would be a chain terminating reaction. 

BetMIC is characterized by two key properties first, the good leaving ability of the benzotriazole (Bet) moiety and, second, the high acidity of the methylene protons. BetMIC is reactive with ketones to afford 4-ethoxy-2-oxazolines (94), which can be hydrolyzed to synthetically useful a-hydroxyaldehydes (95). It must be noted that unlike TosMIC, BetMIC forms 94/96 without the presence of highly toxic thallium alkoxides. The reaction works well in the absence of ethanol and provides better yields when using aliphatic ketones. With aromatic ketones, for example, ben-zophenone, partial conversion to oxazoline occurs probably due to steric effects. Reaction of BetMIC with aldehydes typically generates oxazoles 97 (Scheme 7.24) [43,44]. 

Loesch H J and Remscheid A 1990 Brute force in molecular reaction dynamics a novel technique for measuring steric effects J. Chem. Phys. 93 4779-90... 

Taft then noted that the tetrahedral intermediates of both reactions differ by only two protons, suggesting that the steric effect in both reactions is expected to be the same. Taking the difference in these reaction rates, thus allowed the quantification of the inductive effect. 

The roles of phosphines are not clearly understood and are unpredictable. Therefore, in surveying optimum conditions of catalytic reactions, it is advisable to test the activity of all these important types of phosphines and phosphites. which have different steric effects and electron-donating properties. 

The amino group activates the thiazole ring toward electrophilic centers. This point is illustrated by the rate constants of the reaction between 2-dialkylaminothiazoles (32) and methyl iodide in nitromethane at 25 C (Scheme 23) (158). The steric effects of substituents on nitrogen are... 

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 HSAB pattern may also be reversed by steric effects a Japanese patent describes the preparation of 3-(4-R-thiazolyl-2)thioallophanic acid esters (151) by reaction between 2-amino-4-R-thiazoles (4-R = H or low alkyl) and isothiocyanate formic acid ester (Scheme 96) (309). 

The quatemization reaction of the thiazole nitrogen has been used to evaluate the steric effect of substituents in heterocyclic compounds since thiazole and its alkyl derivatives are good models for such study. In fact, substituents in the 2- and 4-positions of the ring only interact through their steric effects (inductive and resonance effects were constant in the studied series). The thiazole ring is planar, and the geometries of the ground and transition states are identical. Finally, the 2- and 4-positions have been shown to be different (259. 260). 

If the rate constants for quaternization of 2-alkylthiazoles depended on electronic factors, they would all be greater than that of thiazole, which has the low est pK. and all of the same order. The decrease in rate constants that is observed is attributed wholly to steric effects. In Table III-50 we report the main parameters for the reaction of 2-alkylthiazoles with methyl iodide. 

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... 

For most vinyl polymers, head-to-tail addition is the dominant mode of addition. Variations from this generalization become more common for polymerizations which are carried out at higher temperatures. Head-to-head addition is also somewhat more abundant in the case of halogenated monomers such as vinyl chloride. The preponderance of head-to-tail additions is understood to arise from a combination of resonance and steric effects. In many cases the ionic or free-radical reaction center occurs at the substituted carbon due to the possibility of resonance stabilization or electron delocalization through the substituent group. Head-to-tail attachment is also sterically favored, since the substituent groups on successive repeat units are separated by a methylene... 

The way out of this dilemma is easily stated, although not easily acted upon. It is not adequate to consider any one of these approaches for the explanation of something as complicated as these reactions. Polarity effects and resonance are both operative, and, if these still fall short of explaining all observations, there is another old standby to fall back on steric 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. 

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 ... 

The steric effects in isocyanates are best demonstrated by the formation of flexible foams from TDI. In the 2,4-isomer (4), the initial reaction occurs at the nonhindered isocyanate group in the 4-position. The unsymmetrically substituted ureas formed in the subsequent reaction with water are more soluble in the developing polymer matrix. Low density flexible foams are not readily produced from MDI or PMDI enrichment of PMDI with the 2,4 -isomer of MDI (5) affords a steric environment similar to the one in TDI, which allows the production of low density flexible foams that have good physical properties. The use of high performance polyols based on a copolymer polyol allows production of high resiHency (HR) slabstock foam from either TDI or MDI (2). 

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. 

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. 

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