Batch and Continuous-Flow One-Pot Processes using Amine Diazotization to Produce Silylated Diazo Reagents

Area of Science:

• Organic Chemistry
• Synthetic Chemistry

Background:

• Diazomethane reagents are valuable in organic synthesis.
• Existing methods for synthesizing diazomethane derivatives can be hazardous or inefficient.

Purpose of the Study:

• To develop a novel, safe, and efficient synthesis of trimethylsilyldiazomethane (TMSCHN2).
• To explore the applicability of this synthesis for various silicon-bearing diazomethane reagents.
• To demonstrate the utility of TMSCHN2 in one-pot reactions and continuous flow processes.

Main Methods:

• Diazotization of trimethylsilylmethylamine (TMSCH2NH2) using batch and continuous flow synthesis.
• Reaction of other silylated methylamines under developed conditions.
• One-pot esterification and 1,3-dipolar cycloaddition reactions in batch and continuous flow.
• Continuous flow esterification of carboxylic acids.

Main Results:

• Successful synthesis of TMSCHN2 with a daily production of 275 g (2.4 mol) via continuous flow.
• Synthesis of various silicon-bearing diazomethane reagents.
• Demonstrated applicability in one-pot esterification and 1,3-dipolar cycloaddition reactions.
• High-yielding continuous flow esterification of carboxylic acids.
• Reported work-up and purification for a 2-MeTHF solution of TMSCHN2.

Conclusions:

• The developed diazotization method provides an efficient and scalable route to TMSCHN2.
• The process is versatile for synthesizing diverse silicon-bearing diazomethane reagents.
• TMSCHN2 is a valuable reagent for esterification, cycloaddition, methylenation, and homologation reactions, particularly in continuous flow setups.