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
editProtection
editSilylation 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
editDue 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
editSilylation 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
editThe 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
edit
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
editReferences
edit- ^ 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.