Steric effects

Steric effectsarise from the spatial arrangement of atoms. When atoms come close together there is generally a rise in the energy of the molecule. Steric effects are nonbonding interactions that influence the shape (conformation) andreactivityof ions and molecules. Steric effects complementelectronic effects,which dictate the shape and reactivity of molecules. Steric repulsive forces between overlappingelectron cloudsresult in structured groupings of molecules stabilized by the way that opposites attract and like charges repel.

The parentcyclobutadiene(R = H) readilydimerizesbut the R =*tert*-butyl derivative is robust.^[1]

Steric hindrance

Regioselective dimethoxytritylation of the primary 5'-hydroxylgroup ofthymidinein the presence of a free secondary 3'-hydroxy group as a result of steric hindrance due to thedimethoxytritylgroup and theribosering (Py =pyridine).^[2]

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

Steric hindrance between adjacent groups can also affect torsionalbond angles.Steric hindrance is responsible for the observed shape ofrotaxanesand the low rates of racemization of 2,2'-disubstitutedbiphenylandbinaphthylderivatives.

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 bromidesolvolyzes10⁷faster than doesneopentyl bromide.The difference reflects the inhibition of attack on the compound with the sterically bulky(CH₃)₃Cgroup.^[3]

A-values

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

The A-value for amethylgroup is 1.74 as derived from thechemical equilibriumabove. It costs 1.74 kcal/mol for the methyl group to adopt to the axial position compared to the equatorial position.

Substituent	A-Value
H	0
CH₃	1.74
CH₂CH₃	1.75
CH(CH₃)₂	2.15
C(CH₃)₃	>4

Ceiling temperatures

Ceiling temperature( $T_{c}$ ) is a measure of the steric properties of the monomers that comprise a polymer. $T_{c}$ is the temperature where the rate ofpolymerizationanddepolymerizationare equal. Sterically hindered monomers give polymers with low $T_{c}$ 's, which are usually not useful.

Monomer	Ceiling temperature (°C)^[8]	Structure
ethylene	610	CH₂=CH₂
isobutylene	175	CH₂=CMe₂
1,3-butadiene	585	CH₂=CHCH=CH₂
isoprene	466	CH₂=C(Me)CH=CH₂
styrene	395	PhCH=CH₂
α-methylstyrene	66	PhC(Me)=CH₂

Cone angles

Ligand cone angle.

Ligand cone anglesare measures of the size ofligandsincoordination chemistry.It is defined as thesolid angleformed with the metal at the vertex and the hydrogen atoms at the perimeter of the cone (see figure).^[9]

Cone angles of commonphosphineligands
Ligand	Angle (°)
PH₃	87
P(OCH₃)₃	107
P(CH₃)₃	118
P(CH₂CH₃)₃	132
P(C₆H₅)₃	145
P(cyclo-C₆H₁₁)₃	179
P(t-Bu)₃	182
P(2,4,6-Me₃C₆H₂)₃	212

Significance and applications

Steric effects are critical tochemistry,biochemistry,andpharmacology.In organic chemistry, steric effects are nearly universal and affect the rates and activation energies of mostchemical reactionsto varying degrees.

In biochemistry, steric effects are often exploited in naturally occurring molecules such asenzymes,where thecatalyticsite may be buried within a largeproteinstructure. In pharmacology, steric effects determine how and at what rate adrugwill interact with its target bio-molecules.

Prominent sterically hindered compounds
Tris(2,4-di-tert-butylphenyl)phosphite,a widely usedstabilizerin polymers.
Tricyclohexylphosphine,a bulkyphosphine ligandused inhomogeneous catalysisand, withB(C₆F₅)₃,comprises the classicfrustrated Lewis pair.^[10]
2,6-Di-tert-butylphenolis used industrially asUVstabilizers andantioxidantsforhydrocarbon-based products ranging from petrochemicals to plastics.^[11]
Hindered amine light stabilizersare widely used in polymers.^[12]^[13]
Titanium isopropoxideis a monomer, the correspondingtitanium ethoxideis a tetramer.
An isolable selenenic acid owing to steric protection.^[14]

The steric effect of tri-(tert-butyl)aminemakeselectrophilicreactions, like forming the tetraalkyl ammoniumcation, difficult. It is difficult for electrophiles to get close enough to allow attack by thelone pairof the nitrogen (nitrogen is shown in blue)

References

^Günther Maier; Stephan Pfriem; Ulrich Schäfer; Rudolf Matusch (1978). "Tetra-tert-butyltetrahedrane".Angew. Chem. Int. Ed. Engl.17(7): 520–1.doi:10.1002/anie.197805201.
^Gait, Michael (1984).Oligonucleotide synthesis: a practical approach.Oxford: IRL Press.ISBN 0-904147-74-6.
^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
^E.L. Eliel, S.H. Wilen and L.N. Mander, Stereochemistry of Organic Compounds, Wiley, New York (1994).ISBN 81-224-0570-3
^Eliel, E.L.; Allinger, N.L.; Angyal, S.J.; G.A., Morrison (1965).Conformational Analysis.New York: Interscience Publishers.
^Hirsch, J.A. (1967).Topics in Stereochemistry(first ed.). New York: John Wiley & Sons, Inc. p. 199.
^Romers, C.; Altona, C.; Buys, H.R.; Havinga, E. (1969).Topics in Stereochemistry(fourth ed.). New York: John Wiley & Sons, Inc. p. 40.
^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.
^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.
^Stephan, Douglas W. "Frustrated Lewis pairs": a concept for new reactivity and catalysis. Org. Biomol. Chem. 2008, 6, 1535–1539.doi:10.1039/b802575b
^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. pp. a19_313.doi:10.1002/14356007.a19_313.ISBN 3-527-30673-0.
^Pieter Gijsman (2010). "Photostabilisation of Polymer Materials". In Norman S. Allen (ed.).Photochemistry and Photophysics of Polymer Materials Photochemistry.Hoboken: John Wiley & Sons. pp. 627–679.doi:10.1002/9780470594179.ch17.ISBN 978-0-470-59417-9..
^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.pp. o18_o03.doi:10.1002/14356007.o18_o03.ISBN 978-3-527-30673-2.
^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.

External links

Steric Effects (chem.swin.edu.au)at theWayback Machine(archived July 25, 2008)
Steric: A Program to Calculate the Steric Size of Molecules (gh.wits.ac.za)at theWayback Machine(archived December 22, 2017)

[1] Günther Maier; Stephan Pfriem; Ulrich Schäfer; Rudolf Matusch (1978). "Tetra-tert-butyltetrahedrane".Angew. Chem. Int. Ed. Engl.17(7): 520–1.doi:10.1002/anie.197805201.

[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

[ElielWilen-4] E.L. Eliel, S.H. Wilen and L.N. Mander, Stereochemistry of Organic Compounds, Wiley, New York (1994).ISBN 81-224-0570-3

[ElielAllinger-5] Eliel, E.L.; Allinger, N.L.; Angyal, S.J.; G.A., Morrison (1965).Conformational Analysis.New York: Interscience Publishers.

[Hirsch-6] Hirsch, J.A. (1967).Topics in Stereochemistry(first ed.). New York: John Wiley & Sons, Inc. p. 199.

[RomersAltona-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.

[tolman1970-9] 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. pp. a19_313.doi:10.1002/14356007.a19_313.ISBN 3-527-30673-0.

[12] Pieter Gijsman (2010). "Photostabilisation of Polymer Materials". In Norman S. Allen (ed.).Photochemistry and Photophysics of Polymer Materials Photochemistry.Hoboken: John Wiley & Sons. pp. 627–679.doi:10.1002/9780470594179.ch17.ISBN 978-0-470-59417-9..

[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.pp. o18_o03.doi:10.1002/14356007.o18_o03.ISBN 978-3-527-30673-2.

[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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