Steric effects

Steric effects are nonbonding interactions that influence the shape (conformation) and reactivity of ions and molecules. Steric effects complement electronic effects, which dictate the shape and reactivity of molecules. Steric repulsive forces between overlapping electron clouds result in structured groupings of molecules stabilized by the way that opposites attract and like charges repel.

The parent cyclobutadiene (R = H) readily dimerizes but the R = tert-butyl derivative is robust.[1]

Steric hindrance
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).[2]

Steric hindrance is a consequence of steric effects. Steric hindrance is the slowing of chemical reactions due to steric bulk. It is usually manifested in intermolecular reactions, whereas discussion of steric effects often focus on intramolecular interactions. Steric hindrance is often exploited to control selectivity, such as slowing unwanted side-reactions.

Steric hindrance between adjacent groups can also affect torsional bond angles. Steric hindrance is responsible for the observed shape of rotaxanes and the low rates of racemization of 2,2'-disubstituted biphenyl and binaphthyl derivatives.

Measures of steric properties

Because steric effects have profound impact on properties, the steric properties of substituents have been assessed by numerous methods.

Rate data

Relative rates of chemical reactions provide useful insights into the effects of the steric bulk of substituents. Under standard conditions methyl bromide solvolyzes 107 faster than does neopentyl bromide. The difference reflects the inhibition of attack on the compound with the sterically bulky (CH3)3C group.[3]

A-values

A values provide another measure of the bulk of substituents. A values are derived from equilibrium measurements of monosubstituted cyclohexanes.[4][5][6][7] The extent that a substituent favors the equatorial position gives a measure of its bulk.

The A-value for a methyl group is 1.74 as derived from the chemical equilibrium above. It costs 1.74 kcal/mol for the methyl group to adopt to the axial position compared to the equatorial position.
SubstituentA-Value
H0
CH31.74
CH2CH31.75
CH(CH3)22.15
C(CH3)3>4

Ceiling temperatures

Ceiling temperature () is a measure of the steric properties of the monomers that comprise a polymer. is the temperature where the rate of polymerization and depolymerization are equal. Sterically hindered monomers give polymers with low 's, which are usually not useful.

MonomerCeiling temperature (°C)[8]Structure
ethylene610CH2=CH2
isobutylene175CH2=CMe2
1,3-butadiene585CH2=CHCH=CH2
isoprene466CH2=C(Me)CH=CH2
styrene395PhCH=CH2
α-methylstyrene66PhC(Me)=CH2

Cone angles
Ligand cone angle.
Cone angles of common phosphine ligands
LigandAngle (°)
PH387
P(OCH3)3107
P(CH3)3118
P(CH2CH3)3132
P(C6H5)3145
P(cyclo-C6H11)3179
P(t-Bu)3182
P(2,4,6-Me3C6H2)3212

Ligand cone angles are measures of the size of ligands in coordination chemistry. It is defined as the solid angle formed with the metal at the vertex and the hydrogen atoms at the perimeter of the cone (see figure).[9]

Significance and applications

Steric effects are 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.

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.

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)

See also

References
  1. Günther Maier, Stephan Pfriem, Ulrich Schäfer, Rudolf Matusch (1978). "Tetra-tert-butyltetrahedrane". Angew. Chem. Int. Ed. Engl. 17: 520–1. doi:10.1002/anie.197805201.CS1 maint: uses authors parameter (link)
  2. Gait, Michael (1984). Oligonucleotide synthesis: a practical approach. Oxford: IRL Press. ISBN 0-904147-74-6.
  3. Smith, Michael B.; March, Jerry (2007), Advanced Organic Chemistry: Reactions, Mechanisms, and Structure (6th ed.), New York: Wiley-Interscience, ISBN 978-0-471-72091-1
  4. E.L. Eliel, S.H. Wilen and L.N. Mander, Stereochemistry of Organic Compounds, Wiley, New York (1994). ISBN 81-224-0570-3
  5. Eliel, E.L.; Allinger, N.L.; Angyal, S.J.; G.A., Morrison (1965). Conformational Analysis. New York: Interscience Publishers.
  6. Hirsch, J.A. (1967). Topics in Stereochemistry (first ed.). New York: John Wiley & Sons,Inc. p. 199.
  7. Romers, C.; Altona, C.; Buys, H.R.; Havinga, E. (1969). Topics in Stereochemistry (fourth ed.). New York: John Wiley & Sons,Inc. p. 40.
  8. Stevens, Malcolm P. (1999). "6". Polymer Chemistry an Introduction (3rd ed.). New York: Oxford University Press. pp. 193–194. ISBN 978-0-19-512444-6.
  9. Tolman, Chadwick A. (1970-05-01). "Phosphorus ligand exchange equilibriums on zerovalent nickel. Dominant role for steric effects". J. Am. Chem. Soc. 92 (10): 2956–2965. doi:10.1021/ja00713a007.
  10. Stephan, Douglas W. "Frustrated Lewis pairs": a concept for new reactivity and catalysis. Org. Biomol. Chem. 2008, 6, 1535-1539. doi:10.1039/b802575b
  11. Helmut Fiege, Heinz-Werner Voges, Toshikazu Hamamoto, Sumio Umemura, Tadao Iwata, Hisaya Miki, Yasuhiro Fujita, Hans-Josef Buysch, Dorothea Garbe, Wilfried Paulus (2002). "Phenol Derivatives". Ullmann's Encyclopedia of Industrial Chemistry. Weinheim: Wiley-VCH. doi:10.1002/14356007.a19_313.CS1 maint: uses authors parameter (link)
  12. Pieter Gijsman (2010). "Photostabilisation of Polymer Materials". In Norman S. Allen (ed.). Photochemistry and Photophysics of Polymer Materials Photochemistry. Hoboken: John Wiley & Sons. doi:10.1002/9780470594179.ch17.CS1 maint: uses authors parameter (link).
  13. Klaus Köhler; Peter Simmendinger; Wolfgang Roelle; Wilfried Scholz; Andreas Valet; Mario Slongo (2010). "Paints and Coatings, 4. Pigments, Extenders, and Additives". Ullmann's Encyclopedia Of Industrial Chemistry. doi:10.1002/14356007.o18_o03.
  14. Goto, Kei; Nagahama, Michiko; Mizushima, Tadashi; Shimada, Keiichi; Kawashima, Takayuki; Okazaki, Renji (2001). "The First Direct Oxidative Conversion of a Selenol to a Stable Selenenic Acid: Experimental Demonstration of Three Processes Included in the Catalytic Cycle of Glutathione Peroxidase". Organic Letters. 3 (22): 3569–3572. doi:10.1021/ol016682s. PMID 11678710.
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