I am trying to synthesize Aminated PEG (NH2-PEG-OCH3) using P-amino benzoic acid to replace the tosyl group on peg-tosylate via nucleophillic substitution reaction. I think both amine and carboxylate groups on PABA can act as a nucleophile, however amine group has more chances of acting as a nucleophile but still the probability of carboxylate group as a nucleophile cannot be ruled out. In NMR data I can't tell whether the nucleophillic reaction is occuring via the amine or the carboxylate group. FT-IR data can support that but I didn't get any peak of ester group. Can someone tell me any other method to confirm that the nucleophillic substitution took place via carboxylate group and amine group is free for further conjugation?
Or if there is any other way to convert tosyl into amine, I don't want to convert tosyl in azide as it involves using DMF and it is not possible for me to remove DMF using rotavapor.
13C NMR should distinguish between -O-CH2-CH2- and >N-CH2-CH2- products. In PhNHCH2CH2OH, the aliphatic carbon bound to N has a chemical shift of about 45 ppm, and the O-bound carbon shows up at about 60 ppm. In PhC(O)OCH2-CH2-OH, the aliphatic carbon in the ester shows up at about 63 ppm.
If selectivity in this bond-forming reaction is a problem, you might be able to react the tosylate with ammonia, and then arylate the primary amine with 4-bromobenzoic acid (or 4-iodobenzoic acid) a palladium catalyst, and some excess weak base (like diisopropylethylamine or postassium carbonate)
Just a dumb question, and I hope Aaron can help me here: When I think of the reaction as described, I almost want to think that the amino end in PABA would be the first to react. Instead of performing the reaction in the manner described, can't one take the tosylate (or any leaving group for that matter) on the acid end of PABA, and react it with the salt of the PEG, thereby ensuring the reaction proceeds in the desired manner?
I would also expect the amine to be more nucleophilic than the carboxylate, but if it is protonated, then the carboxylate will be more nucleophilic than the ammonium... There are reports of PABA reacting with aliphatic electrophiles under basic conditions, preferentially forming N-C bonds by SN2 type chemistry.
In the research article they have used basic conditions (potassium carbonate and in another reaction they have also added potassium iodide) so the nucleophilic attack should be by carboxylate, I'll do 13C NMR as suggested by Aaron. BTW the authors of the research article have also stated that the chemical shift of COOCH2 in 1H-NMR is larger than 4.0 (which I'm getting too), while the chemical shift of RCH2NPh will be smaller than 4.0.
Varun tosylate is better leaving group.. You can react your tosylated peg with excess of amonia to give corresponding amine. Try to find suitable reference for reaction conditions of amonia reaction with tosylates.. Gud luck
You have to perform two step reaction in order to convert Ts group to amine. First convert Ts to azide by reacting Sod. azide in DMF at elevated temperature. Azide group can easily be converted to amine by PPh3 in MeoH (Staudinger Reaction).
I know this is late but some others can benefit from it.
sincerely,
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