Recently, I've seen in a patent a simple N-alkylation reaction of 2-aminobenzothiazole with ethyl bromoacetate. The inventors have carried out N-formylation reaction first followed by coupling with ethyl bromoacetate. So, I wonder why they did not react the free amino group directly with ethyl bromoacetate? Were they afraid of another side cyclization reaction? If so, what is the role of formyl group in this reaction and also to prevent this side reaction?
Many thanks and sorry for that long question...!!!
With the non formylated system you would get significant statistical problems in mono alkylation. In addition to the desired product, the bis alkylated product would also be observed as a significant byproduct. The formylated system can only be alkylated once, and results in a cleaner reaction overall.
According to my experiments, when I was using 4-bromo aniline to do Sonogashira coupling with 4-ethylnyl anisole, this reaction always failed. but I succeeded in coupling N-(4-iodophenyl)acetamide with 4-ethylnyl anisole.
Many thanks Eric B. J. Harris but, do you have some helpful references in this reaction???
http://en.wikipedia.org/wiki/Acetic_formic_anhydride
there is a reference to Organic Syntheses.
Hi Ahmed: I'm very curious about that as well. Would you mind to share the link of that patent or paste the page here? Thanks.
NEW AMINO-ALKYL-AMIDE DERIVATIVES AS CCR3 RECEPTOR LIGANDS.
Pub. No.: US 2008/0280961 A1
Alkylation of free 2-aminobenzothiazle with haloesters or haloketones will result in alkylation of the ring nitrogen, rather than the 2-amino group. (See, e.g., US 7,601,846).
Formylation allows ready generation of the N-anion, which reacts at the desired position.
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