Triisopropylsilyl chloride
[CAS# 13154-24-0]

Identification

• Classification: Chemical reagent >> Organic reagent >> Silane
• Name: Triisopropylsilyl chloride
• Synonyms: Chlorotriisopropylsilane; Triisopropylchlorosilane
• Molecular Formula: C₉H₂₁ClSi
• Molecular Weight: 192.80
• CAS Registry Number: 13154-24-0
• EC Number: 603-492-0
• SMILES: CC(C)[Si](C(C)C)(C(C)C)Cl

Properties

• Density: 0.901
• Boiling point: 198 °C (739 torr)
• Refractive index: 1.452-1.454
• Flash point: 62 °C

Safety Data

• Hazard Symbols: GHS05 Danger
• Risk Statements: H314
• Safety Statements: P260-P264-P280-P301+P330+P331-P302+P361+P354-P304+P340-P305+P354+P338-P316-P321-P363-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Skin corrosion	Skin Corr.	1B	H314
Serious eye damage	Eye Dam.	1	H318
Skin corrosion	Skin Corr.	1A	H314
Specific target organ toxicity - single exposure	STOT SE	3	H335
Substances or mixtures corrosive to metals	Met. Corr.	1	H290
Skin irritation	Skin Irrit.	2	H315

Discovery and Applications

Triisopropylsilyl chloride (TIPS-Cl) was synthesized in the mid-20th century as part of efforts to develop efficient silyl protecting groups for organic synthesis. Chemists aimed to create a bulky, sterically hindered silyl group to protect functional groups like alcohols and amines from unwanted reactions. TIPS-Cl's ability to form stable, easily removable protecting groups under mild conditions made it a significant advancement. Its introduction enabled chemists to carry out complex, multi-step syntheses with greater control, enhancing the efficiency and selectivity of various synthetic procedures.

TIPS-Cl is commonly used to protect alcohols, phenols, and amines during organic synthesis. Its bulkiness prevents unwanted side reactions and provides excellent stability under a wide range of reaction conditions. For instance, in the synthesis of complex natural products or pharmaceuticals, protecting hydroxyl or amine groups with TIPS allows chemists to perform multiple reaction steps without interference from these functional groups, preserving their integrity until the final stages. Its steric bulk enables selective protection of specific functional groups within a molecule, which is crucial in multi-step synthesis involving molecules with multiple reactive sites. This selective protection allows for precise manipulation of different parts of the molecule sequentially, which is particularly valuable in constructing complex molecular architectures. TIPS groups can be removed under mild conditions, typically using fluoride reagents like tetrabutylammonium fluoride (TBAF). This gentle deprotection is advantageous for sensitive molecules, minimizing the risk of degradation or side reactions. The mild removal conditions make TIPS-Cl an attractive choice for protecting groups, particularly in delicate synthetic sequences.

In pharmaceuticals, TIPS-Cl is used to protect hydroxyl and amine groups in drug molecules during synthesis. This protection allows for the modification and assembly of complex drug structures that might otherwise be unstable or reactive under the conditions required for their formation. For example, in synthesizing antiviral or anticancer agents, TIPS-Cl helps maintain the integrity of functional groups during the rigorous chemical transformations needed to build these complex molecules. TIPS-Cl is utilized to protect amino groups in peptide synthesis, facilitating the construction of peptide chains by preventing unwanted side reactions. Its use ensures that amino acids and peptide fragments can be linked together efficiently, improving the overall yield and purity of the resulting peptides, which are important in drug development and biochemical research.

TIPS-Cl is used to modify polymers, enhancing their properties such as solubility and stability. In polymer synthesis, TIPS groups can introduce functionalities that improve the material's performance, making it suitable for applications like coatings, adhesives, and advanced composites. For instance, incorporating TIPS into a polymer backbone can impart desirable mechanical and chemical resistance properties, beneficial for high-performance materials. TIPS-Cl is applied to modify surfaces, imparting hydrophobicity and chemical resistance. This application is valuable for creating water-repellent and corrosion-resistant coatings, which are used in industries ranging from electronics to construction. For example, TIPS-modified surfaces are used to prevent corrosion in metal components exposed to harsh environmental conditions.

In analytical chemistry, TIPS-Cl is used to derivatize analytes to enhance their volatility and detectability in gas chromatography (GC) and mass spectrometry (MS). This application is crucial for analyzing complex samples, where derivatization improves the separation and identification of components, leading to more accurate and sensitive analysis. For instance, TIPS-Cl can be used to derivatize steroid hormones for better resolution in GC-MS analysis.

References

1976. General laws of the interaction of the silanol groups of silica with alkylchlorosilanes of the ClnSi(CH3)4−n (n=0-4) series. Theoretical and Experimental Chemistry, 12(2).
DOI: 10.1007/bf00526712

2023. Organosilicon Derivatives of β-D-Ribofuranoside: Synthesis, Pharmacological Study, and Insecticidal Activity. Russian Journal of General Chemistry, 93(13).
DOI: 10.1134/s1070363223130297

1993. Oligoribonucleotide synthesis. The silyl-phosphoramidite method. Methods in Molecular Biology.
DOI: 10.1385/0-89603-281-7:81