Steric effects

See also: intramolecular forces
The steric effect of tri-(tert-butyl)amine makes electrophilic reactions, like forming the tetraalkylammonium cation, difficult. It is difficult for electrophiles to get close enough to allow attack by the lone pair of the nitrogen (nitrogen is shown in blue)

Steric effects arise from a fact that each atom within a molecule occupies a certain amount of space. If atoms are brought too close together, there is an associated cost in energy due to overlapping electron clouds (Pauli or Born repulsion), and this may affect the molecule's preferred shape (conformation) and reactivity.

Types

Steric hindrance

Steric hindrance occurs when the large size of groups within a molecule prevents chemical reactions that are observed in related molecules with smaller groups. Although steric hindrance is sometimes a problem (it prevents SN2 reactions with tertiary substrates from taking place), it can also be a very useful tool, and is often exploited by chemists to change the reactivity pattern of a molecule by stopping unwanted side-reactions (steric protection) or by leading to a preference for one stereochemical reaction course as in diastereoselectivity. Steric hindrance between adjacent groups can also restrict torsional bond angles. However, hyperconjugation has been suggested as an explanation for the preference of the staggered conformation of ethane because the steric hindrance of the small hydrogen atom is far too small.[1][2] This is the effect responsible for the observed shape of rotaxanes.

Regioselective dimethoxytritylation of the primary 5'-hydroxyl group of thymidine in the presence of a free secondary 3'-hydroxy group as a result of steric hindrance due to the dimethoxytrityl group and the ribose ring (Py = pyridine).[3]

When a Lewis acid and Lewis base cannot combine due to steric hindrance, they are said to form a frustrated Lewis pair.[4]

Other steric effects

Steric shielding occurs when a charged group on a molecule is seemingly weakened or spatially shielded by less charged (or oppositely charged) atoms, including counterions in solution (Debye shielding). In some cases, for an atom to interact with sterically shielded atoms, it would have to approach from a vicinity where there is less shielding, thus controlling where and from what direction a molecular interaction can take place.

Steric attraction occurs when molecules have shapes or geometries that are optimized for interaction with one another. In these cases molecules will react with each other most often in specific arrangements.

Chain crossing: A chain, ring, or a set of rings cannot change from one conformation to another if it would require a chain (or ring - a ring is a cyclic chain) to pass through itself or another chain. This effect, or lack of, is responsible for the shape of catenanes and molecular knots.

Steric repulsions between different parts of a molecular system were found to be of key importance in governing the direction of transition-metal-mediated transformations and catalysis. Steric effects can even induce a mechanism switch in the catalytic reaction.[5] Steric repulsion is also largely responsible for the stabilizing of colloids by coating the surface with a polymer, and can also cause bond length shortening, and compressional frequency enhancement in the IR spectrum.[6]

Steric inhibition of resonance is present only in benzene rings. The presence of any group at the ortho position in benzoic acid will throw the carboxylic acid group out of the plane, and thus its mesomeric connection with the benzene ring vanishes. This means that ortho-substituted benzoic acids are stronger than meta- and para-substituted benzoic acids.

Steric inhibition of protonation

Consider 2,2,6,6-Tetramethylpiperidine and in,in-diphosphine.[7]

Distinction from electronic effects

The structure, properties, and reactivity of a molecule is dependent on straightforward bonding interactions including covalent bonds, ionic bonds, hydrogen bonds and lesser forms of bonding. This bonding supplies a basic molecular skeleton that is modified by repulsive forces. These repulsive forces include the steric interactions described above. Basic bonding and steric are at times insufficient to explain many structures, properties, and reactivity. Thus steric effects are often contrasted and complemented by electronic effects implying the influence of effects such as induction, conjunction, orbital symmetry, electrostatic interactions, and spin state. There are more esoteric electronic effects but these are among the most important when considering structure and chemical reactivity.

A special computational procedure was developed to separate electronic and steric effects of an arbitrary group in the molecule and to reveal their influence on structure and reactivity.[8]

Significance

Understanding steric effects is critical to chemistry, biochemistry and pharmacology. In organic chemistry, steric effects are nearly universal and affect the rates and activation energies of most chemical reactions to varying degrees. Steric effects often dictate reaction pathways in organic synthesis because there are fewer configurations in which molecules can collide and successfully react. In surface chemistry, steric effects manifest in an entropic contribution to the overall Gibbs energy. Hence, colloidal stability can be obtained by steric shielding from polymers, often made possible via block co-polymer adsorption or grafting polymer onto charged nanoparticles. This spatial shielding effect is large-scale in comparison to Debye shielding due to the size of the attached polymer strands. In biochemistry, steric effects are often exploited in naturally occurring molecules such as enzymes, where the catalytic site may be buried within a large protein structure. In pharmacology, steric effects determine how and at what rate a drug will interact with its target bio-molecules.

Note the organic chemical example of Stereochemistry of ketonization of enols and enolates where diastereoselectivity results from steric hindrance.

See also

References

  1. ↑ Pophristic, Vojislava; Goodman, Lionel (2001). "Hyperconjugation not steric repulsion leads to the staggered structure of ethane". Nature 411 (6837): 565–8. doi:10.1038/35079036. PMID 11385566.
  2. ↑ Weinhold, Frank (2001). "Chemistry. A new twist on molecular shape". Nature 411 (6837): 539–41. doi:10.1038/35079225. PMID 11385553.
  3. ↑ Gait, Michael (1984). Oligonucleotide synthesis: a practical approach. Oxford: IRL Press. ISBN 0-904147-74-6.
  4. ↑ Stephan, Douglas W. "Frustrated Lewis pairs": a concept for new reactivity and catalysis. Org. Biomol. Chem. 2008, 6, 1535-1539. doi:10.1039/b802575b
  5. ↑ Ananikov, Valentin P.; Szilagyi, Robert; Morokuma, Keiji; Musaev, Djamaladdin G. (2005). "Can Steric Effects Induce the Mechanism Switch in the Rhodium-Catalyzed Imine Boration Reaction? A Density Functional and ONIOM Study". Organometallics 24 (8): 1938. doi:10.1021/om049156o.
  6. ↑ Zong, J., J. T. Mague, and R. A. Pascal, Jr., Exceptional Steric Congestion in an in,in-Bis(hydrosilane), J. Am. Chem. Soc. 2013, 135, 13235-13237.http://DOI: 10.1021/ja407398w
  7. ↑ Zong, J., Mague, J. T., Kraml, C. M., & Pascal Jr, R. A. (2013). "A Congested in, in-Diphosphine." Organic letters, 15(9), 2179-2181. DOI: 10.1021/ol400728m
  8. ↑ Ananikov, Valentine P.; Musaev, Djamaladdin G.; Morokuma, Keiji (2007). "Critical Effect of Phosphane Ligands on the Mechanism of Carbon–Carbon Bond Formation Involving Palladium(II) Complexes: A Theoretical Investigation of Reductive Elimination from Square-Planar and T-Shaped Species". European Journal of Inorganic Chemistry 2007 (34): 5390. doi:10.1002/ejic.200700850.

External links

This article is issued from Wikipedia - version of the Thursday, January 14, 2016. The text is available under the Creative Commons Attribution/Share Alike but additional terms may apply for the media files.