Steric hindrance mechanism

C. A. Johnson and P. H. Gross, Heterocyclic amino sugar derivatives. 6. Stabilization of a reactive intermediate by steric hindrance. Mechanism of 3,6-anhydro sugar formation, J. Org. Chem., 38 (1973) 2509-2512. 

A second mechanism of preferential exclusion is based on the steric properties of the protein and cosolvent. The three-dimensional structure of the cosolvent may hinder interactions with the protein surface. High-molecular-weight cosolvents like polyethylene glycols (PEGs) and other proteins may be preferentially excluded through this steric hindrance mechanism. 

Flow-assisted methods typically utilize steric hindrance mechanisms in which microchannels or microstructures form barriers to move particles out of their streamlines and into a desired equilibrium position. The steric hindrance mechanism allows size separation of micron and submicron... 

Figure 1. Hydrophoretic separation principle, (a) Schematic showing a hydrophoretic device with anisotropic microfluidic obstacles, (b and c) Simulated streamlines in the device. The slanted groove patterns on the channel generate rotational flows by using a steady axial pressure gradient, (d) Different particle ordering according to particle size by steric hindrance mechanism. (Reproduced with permission from Ref [20] Copyright 2009, American Chemical Society.)...

Steric hindrance Physical separation of particles in a fluid suspension. Specifically, the hindrance to flocculation of a steric mechanism or arrangement of molecules. The steric hindrance mechanism typically relies on an adsorbed organic layer on particle surfaces that physically prohibits primary particles from touching each other. 

The simplest and most quickly computed models are those based solely on steric hindrance. Unfortunately, these are often too inaccurate to be trusted. Molecular mechanics methods are often the method of choice due to the large amount of computation time necessary. Semiempirical methods are sometimes used when molecular mechanics does not properly represent the molecule. Ah initio methods are only viable for the very smallest molecules. These are discussed in more detail in the applicable chapters and the sources mentioned in the bibliography. 

Having just learned that tertiary alkyl halides are practically inert to substitution by the Sn2 mechanism because of steric hindrance we might wonder whether they undergo nucleophilic substitution at all We 11 see m this section that they do but by a mecha nism different from 8 2... 

As crowding at the carbon that bears the leaving group decreases the rate of nude ophilic attack by the Lewis base increases A low level of steric hindrance to approach of the nucleophile is one of the special circumstances that permit substitution to pre dominate and primary alkyl halides react with alkoxide bases by an 8 2 mechanism m preference to E2... 

Absorption, metaboHsm, and biological activities of organic compounds are influenced by molecular interactions with asymmetric biomolecules. These interactions, which involve hydrophobic, electrostatic, inductive, dipole—dipole, hydrogen bonding, van der Waals forces, steric hindrance, and inclusion complex formation give rise to enantioselective differentiation (1,2). Within a series of similar stmctures, substantial differences in biological effects, molecular mechanism of action, distribution, or metaboHc events may be observed. Eor example, (R)-carvone [6485-40-1] (1) has the odor of spearrnint whereas (5)-carvone [2244-16-8] (2) has the odor of caraway (3,4). 

The azo coupling reaction proceeds by the electrophilic aromatic substitution mechanism. In the case of 4-chlorobenzenediazonium compound with l-naphthol-4-sulfonic acid [84-87-7] the reaction is not base-catalyzed, but that with l-naphthol-3-sulfonic acid and 2-naphthol-8-sulfonic acid [92-40-0] is moderately and strongly base-catalyzed, respectively. The different rates of reaction agree with kinetic studies of hydrogen isotope effects in coupling components. The magnitude of the isotope effect increases with increased steric hindrance at the coupler reaction site. The addition of bases, even if pH is not changed, can affect the reaction rate. In polar aprotic media, reaction rate is different with alkyl-ammonium ions. Cationic, anionic, and nonionic surfactants can also influence the reaction rate (27). 

In the El cb mechanism, the direction of elimination is governed by the kinetic acidity of the individual p protons, which, in turn, is determined by the polar and resonance effects of nearby substituents and by the degree of steric hindrance to approach of base to the proton. Alkyl substituents will tend to retard proton abstraction both electronically and sterically. Preferential proton abstraction from less substituted positions leads to the formation of the less substituted alkene. This regiochemistry is opposite to that of the El reaction. 

Examine space-filling models and electron density surfaces for alkene A and alkene B. For each, which face of the double bond is less hindered Which atoms cause steric hindrance of the alkene Is this reaction controlled by steric hindrance If so, explain which step(s) in the catal3 ic mechanism would be most affected. 

To establish a mechanism for the formation of 33, the reaction has been monitored by H-NMR spectroscopy (91CB2013).Tlie basicity of the azine is a rate-determining effect as well as a steric hindrance. Pyridine is more reactive than pyrimidine. 2-Substituted pyridines do not give the corresponding salts. 

Steric hindrance raises the energy of the Sjv-2 transition state, increasing AG- and decreasing the reaction rate (Figure 11.7a). As a result, SN2 reactions are best for methyl and primary substrates. Secondary substrates react slowly, and tertiary substrates do not react by an S -2 mechanism. 

The mechanism of the alkoxymercuration reaction is similar to that described in Section 7.4 for hvdroxymercuration. The reaction is initiated by electrophilic addition of Iig2+ to the alkene, followed by reaction of the intermediate cation with alcohol and reduction of the C-Hg bond by NaBH4. A variety of alcohols and alkenes can be used in the alkoxymercuration reaction. Primary, secondary, and even tertiary alcohols react well, but ditertiary ethers can t be prepared because of steric hindrance to reaction. 

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