Tert-butyldimethylsilyl chloride

Definition

tert-Butyldimethylsilyl chloride (TBDMS-Cl) is a silylating agent used to protect hydroxyl (OH) groups in organic synthesis. It is a key reagent in the protection of alcohols, a common step in the synthesis of complex organic molecules.

5 Must Know Facts For Your Next Test

1. tert-Butyldimethylsilyl chloride (TBDMS-Cl) is a sterically hindered silylating agent that selectively reacts with primary and secondary alcohols to form silyl ether protecting groups.
2. The tert-butyl group provides steric bulk, making the silyl ether more resistant to cleavage compared to other silyl protecting groups like trimethylsilyl (TMS).
3. TBDMS-Cl is commonly used to protect alcohols in multi-step organic synthesis, as the silyl ether can be selectively removed under mild conditions using fluoride ion sources.
4. The presence of the TBDMS protecting group increases the solubility of the alcohol in organic solvents, facilitating purification and handling during synthetic steps.
5. TBDMS-Cl reacts with alcohols in the presence of a base, such as imidazole, to form the corresponding silyl ether in high yield.

Review Questions

• Explain the role of tert-butyldimethylsilyl chloride (TBDMS-Cl) in the protection of alcohols during organic synthesis.
  • tert-Butyldimethylsilyl chloride (TBDMS-Cl) is a widely used silylating agent that selectively reacts with alcohols to form silyl ether protecting groups. The bulky tert-butyl group on the silicon atom makes the resulting TBDMS ether more resistant to cleavage compared to other silyl protecting groups, such as trimethylsilyl (TMS). This allows the alcohol functionality to be temporarily masked during subsequent synthetic steps, preventing unwanted reactions. The TBDMS protecting group also increases the solubility of the alcohol in organic solvents, facilitating purification and handling of the molecule.
• Describe the reaction mechanism for the formation of a TBDMS ether from an alcohol and TBDMS-Cl.
  • The formation of a TBDMS ether from an alcohol and TBDMS-Cl proceeds via a nucleophilic substitution reaction. The alcohol first reacts with a base, such as imidazole, to generate an alkoxide ion. This nucleophilic alkoxide then attacks the silicon atom of the TBDMS-Cl, displacing the chloride ion and forming the TBDMS ether. The tert-butyl group on the silicon provides steric hindrance, making the TBDMS ether more resistant to cleavage compared to other silyl protecting groups. This allows the alcohol functionality to be selectively protected during subsequent synthetic transformations.
• Discuss the advantages of using TBDMS-Cl as a protecting group for alcohols in multi-step organic synthesis, and explain how the TBDMS group can be selectively removed.
  • The use of tert-butyldimethylsilyl chloride (TBDMS-Cl) as a protecting group for alcohols in organic synthesis offers several advantages. The bulky tert-butyl group provides steric hindrance, making the resulting TBDMS ether more stable and resistant to cleavage compared to other silyl protecting groups. This allows the alcohol functionality to be effectively masked during subsequent synthetic steps, preventing unwanted reactions. Additionally, the TBDMS group increases the solubility of the alcohol in organic solvents, facilitating purification and handling of the molecule. When the protection is no longer needed, the TBDMS group can be selectively removed under mild conditions using fluoride ion sources, such as tetrabutylammonium fluoride (TBAF) or hydrogen fluoride (HF), regenerating the original alcohol functionality.

Related terms

Silyl Ether: A silyl ether is a functional group in organic chemistry where a silicon atom is bonded to an oxygen atom, which is in turn bonded to an alkyl or aryl group. Silyl ethers are commonly used to protect alcohol groups during synthetic transformations.

Protecting Group: A protecting group is a temporary substituent applied to a functional group in a organic molecule to prevent it from undergoing an unwanted reaction during a chemical transformation.

Alcohols: Alcohols are organic compounds containing a hydroxyl (OH) functional group bonded to a saturated carbon atom. They are important functional groups in organic chemistry and play a key role in many chemical reactions.