u/CHKP2025

▲ 3 r/OrganicChemistry+1 crossposts

Guanidinylation reaction

Hi everyone,

I am working on the selective guanidinylation/protection of a diamine-containing intermediate and would appreciate suggestions from people who have experience with polyamine chemistry.

I want to convert both terminal primary amines into bis-Boc protected guanidines using a reagent such as:

N,N′-di-Boc-N″-triflylguanidine or related guanidinylation reagents.

The target compound has:

  1. two guanidine groups

  2. each guanidine protected with two Boc groups

  3. carboxylic acid left untouched

My Questions;

  1. What are the best reaction conditions for this transformation?

solvent?

  1. Is it necessary to protect the carboxylic acid before guanidinylation?

  2. Would DIPEA or Et₃N be sufficient as base, or is stronger base preferred?

  3. Any issues expected from the tertiary amine during guanidinylation?

  4. What purification method worked best for you?

6.Any side reactions or over-guanidinylation problems observed with polyamine substrates?

Any literature references, practical tips, TLC behavior, or workup suggestions would be very helpful. Thanks in advance!

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u/CHKP2025 — 3 days ago