Hi, All
I trying to synthesis peptide with Amine (NH2) and Chlorine including fragment.
I tried second times.
1) just left peptide with amine & 4X chlorine 3h
2) peptide with amine & 4X chlorine & 4X 6M NaOH 3h
After synthesis, I did test-cleavage to check the mass but I could not get the expected mass.
Could you tell me the synthesis method??
Thank you so much!!!
The electrophiles of the type 2-chlorobenzoimidazole are very weak and need drastic conditions for necleophilic substitution with amines. If the amine is a normal amine or aniline without further functionality, temperatures of 130 to 200°C are required.Sometimes the reaction is done in an autoclave. Typical solvents are isoamylalcohol, butanol, acetonitrile, acetonitrile + water, NMP or pyridine. Bases which are used for this rection are pyridine, Hünig base or alkali hydroxides. For your purpose pyridine as solvent and base, eventually combined with water, could be a good choice. Also NMP (+ water) and an organic superbase like DBU could work. At temperature of 100°C you need reaction times of several days or a week. Perhaps assistance with microwave or utrasonic sound helps. But you must face the possibility that it does not work at all. Very drastic conditions would destroy the amino acids or recemize them.
This paper explains side reactions:
https://pdfs.semanticscholar.org/f31b/2efed887c3f2046fdd140acdc274212372ec.pdf
https://digitalcommons.lsu.edu/cgi/viewcontent.cgi?article=3150&context=gradschool_disstheses
Dear Jürgen, if I am right the paper describes the reaction of 2-Chloromethyl-benzimidazole with aminoacid derivatives, but the chloromethyl groups reacts much faster than the chloro substituent directly linked to the heteroaromatic ring. The aliphatic nucleophilic substitution on a reactive chloromethyl groups is not comparable to a nuclephilic aromatic substitution which is planned by Sunga.
Dear Burkhard ,
Thank you for this information.
How about '2-chloropyridine' instead of '2-chlorobenzoimidazole '?
Is it also need heat and long reaction time in NMP?
I don't have any experience like this synthesis at all.
I am not sure if 2-chloropyridine is more reactive but principally there will be the same problems. But it is worth an experiment. Perhaps also refluxing acetonitrile at 80 °C is sufficient. DMSO is another suitable solvent.
- Badges
- Science topic
- Similar topics
- Biological Science
- Biochemistry
- Biomolecules
- Peptides