Alternative solvents for elevated-temperature solid-phase parallel synthesis. Application to thionation of amides.

Area of Science:

• Organic Chemistry
• Synthetic Chemistry
• Process Chemistry

Background:

• Elevated-temperature parallel solid-phase synthesis requires solvents with specific properties.
• Traditional solvents may exhibit high vapor pressure at elevated temperatures, posing challenges.
• Solvent selection is critical for optimizing reaction efficiency and yield in solid-phase synthesis.

Purpose of the Study:

• To investigate a novel class of higher-boiling solvents for high-temperature parallel solid-phase synthesis.
• To evaluate the suitability of these solvents based on vapor pressure and solvent effect tuning.
• To identify an optimal solvent for parallel solid-phase Lawesson's thionation reactions.

Main Methods:

• Investigation of higher-boiling solvents for elevated-temperature applications.
• Assessment of solvent properties including vapor pressure at high temperatures.
• Evaluation of solvent effect tuning capabilities.
• Testing of candidate solvents in parallel solid-phase Lawesson's thionation reactions.

Main Results:

• The new class of higher-boiling solvents exhibits extremely low vapor pressures at high temperatures.
• These solvents provide a broader range of solvent effect tuning compared to conventional options.
• Benzyl benzoate demonstrated superior performance as a high-boiling solvent for the specific reaction.

Conclusions:

• Higher-boiling solvents represent an advantageous alternative for high-temperature parallel solid-phase synthesis.
• Their low vapor pressure and tunable solvent effects enhance process safety and efficiency.
• Benzyl benzoate is identified as a highly effective solvent for parallel solid-phase Lawesson's thionation.