Silylation: Difference between revisions
Added an example image of deprotection |
Expanded the enolate trapping section with more detail and an image. |
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==Protection Chemistry== |
==Protection Chemistry== |
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=== Protection === |
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Silylation is often used to protect alcohols and amines. The products after silylation, namely silyl ethers and silyl amines, are resilient toward basic conditions.<ref>{{Cite book |last=Clayden |first=Jonathan |title=Organic chemistry |last2=Greeves |first2=Nick |last3=Warren |first3=Stuart |date=2012 |publisher=Oxford university press |isbn=978-0-19-927029-3 |edition=2nd |location=Oxford |pages=549-550}}</ref> Protection is typically done by reacting the functional group with a silyl halide by an [[SN2 reaction]] mechanism, typically in the presence of base.<ref>{{Cite journal |last=Pagliano |first=Enea |last2=Campanella |first2=Beatrice |last3=D'Ulivo |first3=Alessandro |last4=Mester |first4=Zoltán |date=September 2018 |title=Derivatization chemistries for the determination of inorganic anions and structurally related compounds by gas chromatography - A review |url=https://linkinghub.elsevier.com/retrieve/pii/S0003267018304227 |journal=Analytica Chimica Acta |language=en |volume=1025 |pages=12–40 |doi=10.1016/j.aca.2018.03.043}}</ref> |
Silylation is often used to protect alcohols and amines. The products after silylation, namely silyl ethers and silyl amines, are resilient toward basic conditions.<ref>{{Cite book |last=Clayden |first=Jonathan |title=Organic chemistry |last2=Greeves |first2=Nick |last3=Warren |first3=Stuart |date=2012 |publisher=Oxford university press |isbn=978-0-19-927029-3 |edition=2nd |location=Oxford |pages=549-550}}</ref> Protection is typically done by reacting the functional group with a silyl halide by an [[SN2 reaction]] mechanism, typically in the presence of base.<ref>{{Cite journal |last=Pagliano |first=Enea |last2=Campanella |first2=Beatrice |last3=D'Ulivo |first3=Alessandro |last4=Mester |first4=Zoltán |date=September 2018 |title=Derivatization chemistries for the determination of inorganic anions and structurally related compounds by gas chromatography - A review |url=https://linkinghub.elsevier.com/retrieve/pii/S0003267018304227 |journal=Analytica Chimica Acta |language=en |volume=1025 |pages=12–40 |doi=10.1016/j.aca.2018.03.043}}</ref> |
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[[File:Bis(trimethylsilyl)acetamide.svg|220px|thumb|[[Bis(trimethylsilyl)acetamide]], a popular reagent for silylation]][[Bis(trimethylsilyl)acetamide]] ("BSA", Me<sub>3</sub>SiNC(OSiMe<sub>3</sub>)Me is an efficient silylation agent. The reaction of BSA with alcohols gives the corresponding trimethyl[[silyl ether]], together with acetamide as a byproduct (Me = CH<sub>3</sub>):<ref>{{cite journal |doi=10.15227/orgsyn.063.0079 |title=2-Methyl-2-(Trimethylsiloxy)pentan-3-one |journal=Organic Syntheses |year=1985 |volume=63 |page=79|first1=Steven D.|last1=Young|first2=Charles T.|last2=Buse|first3=Clayton H.|last3=Heathcock }}</ref> |
[[File:Bis(trimethylsilyl)acetamide.svg|220px|thumb|[[Bis(trimethylsilyl)acetamide]], a popular reagent for silylation]][[Bis(trimethylsilyl)acetamide]] ("BSA", Me<sub>3</sub>SiNC(OSiMe<sub>3</sub>)Me is an efficient silylation agent. The reaction of BSA with alcohols gives the corresponding trimethyl[[silyl ether]], together with acetamide as a byproduct (Me = CH<sub>3</sub>):<ref>{{cite journal |doi=10.15227/orgsyn.063.0079 |title=2-Methyl-2-(Trimethylsiloxy)pentan-3-one |journal=Organic Syntheses |year=1985 |volume=63 |page=79|first1=Steven D.|last1=Young|first2=Charles T.|last2=Buse|first3=Clayton H.|last3=Heathcock }}</ref> |
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:{{chem2|2 ROH + MeC(OSiMe3)NSiMe3 → MeC(O)NH2 + 2 ROSiMe3}} |
:{{chem2|2 ROH + MeC(OSiMe3)NSiMe3 → MeC(O)NH2 + 2 ROSiMe3}} |
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===Deprotection=== |
===Deprotection=== |
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[[File:Silylation Deprotection Scheme.png|545x545px]] |
[[File:Silylation Deprotection Scheme.png|545x545px]] |
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=== Enolate Trapping === |
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| ⚫ | Silylation can also be used to trap reactive compounds for isolation or identification. A common example of this is by trapping reactive enolates as [[Silyl enol ether|silyl enol ethers]], which represent reactive tautomers of many carbonyl compounds.<ref name=":1">{{Cite book |last=Clayden |first=Jonathan |title=Organic chemistry |last2=Greeves |first2=Nick |last3=Warren |first3=Stuart |date=2012 |publisher=Oxford university press |isbn=978-0-19-927029-3 |edition=2nd |location=Oxford |pages=466-467}}</ref> The original enolate can be reformed upon reaction with an organolithium, or other strong base.<ref name=":1" /> |
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[[File:Enolate Trapping by Silylation.png|800x800px]] |
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==Applications in Analysis== |
==Applications in Analysis== |
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Revision as of 07:50, 24 November 2024
Silylation is the introduction of one or more (usually) substituted silyl groups (R3Si) to a molecule. Silylations are core methods for production of organosilicon chemistry. Silanization involves similar methods but usually refers to attachment of silyl groups to solids.[1]
Protection Chemistry
Protection
Silylation is often used to protect alcohols and amines. The products after silylation, namely silyl ethers and silyl amines, are resilient toward basic conditions.[2] Protection is typically done by reacting the functional group with a silyl halide by an SN2 reaction mechanism, typically in the presence of base.[3]
The mechanism involves the replacement of a proton or an anion with a trialkylsilyl group, typically trimethylsilyl (-SiMe3), as illustrated by the synthesis of a trimethylsilyl ethers from alcohols and trimethylsilyl chloride (Me = CH3):
- ROH + Me3SiCl → ROSiMe3 + HCl
acetamide.svg)
Bis(trimethylsilyl)acetamide ("BSA", Me3SiNC(OSiMe3)Me is an efficient silylation agent. The reaction of BSA with alcohols gives the corresponding trimethylsilyl ether, together with acetamide as a byproduct (Me = CH3):[4]
- 2 ROH + MeC(OSiMe3)NSiMe3 → MeC(O)NH2 + 2 ROSiMe3
Deprotection
Due to the strength of the Si-F bond, fluorides are commonly used to deprotect silyl groups via an SN2 mechanism.[5] The primary deprotecting agent is tetra-n-butylammonium fluoride (TBAF), as its aliphatic chains in help incorporate F- into organic solvent.[6][7][8]
Enolate Trapping
Silylation can also be used to trap reactive compounds for isolation or identification. A common example of this is by trapping reactive enolates as silyl enol ethers, which represent reactive tautomers of many carbonyl compounds.[9] The original enolate can be reformed upon reaction with an organolithium, or other strong base.[9]
Applications in Analysis
The introduction of a silyl group(s) gives derivatives of enhanced volatility, making the derivatives suitable for analysis by gas chromatography and electron-impact mass spectrometry (EI-MS). For EI-MS, the silyl derivatives give more favorable diagnostic fragmentation patterns of use in structure investigations, or characteristic ions of use in trace analyses employing selected ion monitoring and related techniques.[10][11]
Of metals
Coordination complexes with silyl ligands are well known. An early example is CpFe(CO)2Si(CH3)3, prepared by silylation of CpFe(CO)2Na with trimethylsilyl chloride. Typical routes include oxidative addition of Si-H bonds to low-valent metals. Metal silyl complexes are intermediates in hydrosilation, a process used to make organosilicon compounds on both laboratory and commercial scales.[12][13]
See also
References
- ^ Pape, Peter G. (2017). "Silylating Agents". Kirk-Othmer Encyclopedia of Chemical Technology. pp. 1–15. doi:10.1002/0471238961.1909122516011605.a01.pub3. ISBN 9780471238966.
- ^ Clayden, Jonathan; Greeves, Nick; Warren, Stuart (2012). Organic chemistry (2nd ed.). Oxford: Oxford university press. pp. 549–550. ISBN 978-0-19-927029-3.
- ^ Pagliano, Enea; Campanella, Beatrice; D'Ulivo, Alessandro; Mester, Zoltán (September 2018). "Derivatization chemistries for the determination of inorganic anions and structurally related compounds by gas chromatography - A review". Analytica Chimica Acta. 1025: 12–40. doi:10.1016/j.aca.2018.03.043.
- ^ Young, Steven D.; Buse, Charles T.; Heathcock, Clayton H. (1985). "2-Methyl-2-(Trimethylsiloxy)pentan-3-one". Organic Syntheses. 63: 79. doi:10.15227/orgsyn.063.0079.
- ^ Clayden, Jonathan; Greeves, Nick; Warren, Stuart (2012). Organic chemistry (2nd ed.). Oxford: Oxford university press. ISBN 978-0-19-927029-3.
- ^ Paquette, Leo A., ed. (1995). Encyclopedia of reagents for organic synthesis. Chichester ; New York: Wiley. ISBN 978-0-471-93623-7.
- ^ Mercedes Amat, Sabine Hadida, Swargam Sathyanarayana, and Joan Bosch "Regioselective Synthesis of 3-Substituted Indoles: 3-Ethylindole" Organic Syntheses 1997, volume 74, page 248. doi:10.15227/orgsyn.074.0248
- ^ Nina Gommermann and Paul Knochel "N,N-Dibenzyl-n-[1-cyclohexyl-3-(trimethylsilyl)-2-propynyl]-amine from Cyclohexanecarbaldehyde, Trimethylsilylacetylene and Dibenzylamine" Organic Syntheses 2007, vol. 84, page 1. doi:10.15227/orgsyn.084.0001
- ^ a b Clayden, Jonathan; Greeves, Nick; Warren, Stuart (2012). Organic chemistry (2nd ed.). Oxford: Oxford university press. pp. 466–467. ISBN 978-0-19-927029-3.
- ^ Luis-Alberto Martin; Ingrid Hayenga. "Silylation of Non-Steroidal Anti-Inflammatory Drugs". sigmaaldrich.com. Retrieved 24 September 2023.
- ^ Blau, Karl; J. M. Halket (1993). Handbook of Derivatives for Chromatography (2nd ed.). John Wiley & Sons. ISBN 0-471-92699-X.
- ^ Moris S. Eisen "Transition-metal silyl complexes" in The Chemistry of Organic Silicon Compounds. Volume 2 Edited by Zvi Rappoport and Yitzhak Apeloig, 1998, John Wiley & Sons
- ^ Corey, Joyce Y.; Braddock-Wilking, Janet (1999). "Reactions of Hydrosilanes with Transition-Metal Complexes: Formation of Stable Transition-Metal Silyl Compounds". Chemical Reviews. 99 (1): 175–292. doi:10.1021/CR9701086. PMID 11848982.