Synthesis
Trimethyltin chloride (370 mg) and anhydrous methanol (5 mL) were added to a dry reaction flask. Then, potassium hydroxide solid (104 mg, 1.9 mmol) was slowly added to the resulting reaction solution. The reaction solution was stirred continuously at ambient temperature for 1 hour. During the reaction, potassium chloride solid was clearly observed to precipitate from the reaction system. After the reaction was complete, the potassium chloride solid precipitate in the reaction mixture was filtered off. The filtrate containing the product was then evaporated and concentrated under reduced pressure under vacuum to obtain the target product molecule, trimethyltin hydroxide.
Figure: Synthetic Route of Trimethyltin Hydroxide
Chemical Properties
Trimethyltin hydroxide is a colorless, white crystals. It is soluble in water and many organic solvents. It is commercially available in the form of large, needle-shaped, crystals with a significant propensity for twinning along the needle axis. The twinning of the trimethyltin hydroxide needle shaped crystals makes finding a single crystal for data collection very difficult.
Uses
Trimethyltin hydroxide is used in the synthesis of modified thymines, which is useful as inhibitors of RNase A. It is also used in the preparation of ketoheterocycle inhibitors of fatty acid amide inhibitors. It reacts with 2,2-disubstituted benzothiazolines to form trialkyltin derivatives of sulphur containing Schiff base complexes.
Reactions
The synthesis of N-Boc-N-(2-(tritylthio)ethoxy)glycine (4) is illustrated in Scheme 2. O-(2-(tritylthio)ethyl)hydroxylamine (1) was synthesized using the literature method. The aminooxy group was then protected with Boc, followed by alkylation with methyl bromoacetate in the presence of sodium hydride. Saponification of the methyl ester with trimethyltin hydroxide afforded N-Boc-N-(2-(tritylthio)ethoxy)glycine (4) in an overall yield of 19% after three steps of reactions. The Boc and Trt protecting groups in building block 4 are stable to Fmoc SPPS and are readily removable by treatment with trifluoroacetic acid (TFA).
References
[1] Anderson, Kirsty M., et al. "Trimethyltin hydroxide: a crystallographic and high Z′ curiosity." Crystal Growth & Design, 2011, 11 3: 820-826. DOI:
10.1021/cg101464j.
[2] K. C. NICOLAOU PROF. DR. A Mild and Selective Method for the Hydrolysis of Esters with Trimethyltin Hydroxide[J]. Angewandte Chemie International Edition, 2005, 44 9: 1378-1382. DOI:
10.1002/anie.200462207.
[3] ROBIN K HARRIS Patrick R Kenneth J Packer. High-resolution Tin-119 NMR of solid trimethyltin hydroxide[J]. Journal of Magnetic Resonance (1969), 1985, 61 3: Pages 564-566. DOI:10.1016/0022-2364(85)90199-4.
[4] LINGLING PENG, AIMIN SONG* N-tert-Butoxycarbonyl-N-(2-(tritylthio)ethoxy)glycine as a Building Block for Peptide Ubiquitination[J]. Bioconjugate Chemistry Bioconjugate, 2024, 35 2: 245-253. DOI:10.1021/acs.bioconjchem.3c00541.
