in amide synthesis with carboxylic acid, I have two compounds, one have a NH2 group and the other one have a NH3+ group, which one is more active? R-NH3+ or R'-NH2?
R-NH2 is more active because it strong nucleophile
Regards
If you're doing a coupling reaction with activated acid or using carbonyl chloride (like acyl chloride, then this reaction will only occur with amine, as salt lacks lone pair to donate to carbonyl carbon in order to establish the bond. Salt will need a base to remove acidic proton from the reaction in order to partisipate in it (in some reactions amines are deliberately acidified to protect them from reaction with acylating or alkylating agent).
Mikhail Nekrasov
Thank you for your answer.
My reaction is between an amine and a peptide which contains a lot of NH3+ group. The yield is quite bad therefore I am wondering if it is because the competition reaction between intra-molecular reaction between COOH and NH3+.
since the salt form cannot react with carboxylic acid, then why people are using Fmoc or Boc to protect NH2 but few people are using salt form?
RNH2 is stronger base than it's salt, so it is stronger nucleophilide than the salt.So amine is more active.
Protecting groups are more reliable than salts and can survive reactions with bases, which are plenty.
If you're just trying to react acid from peptide with amine, it will be hard, because it either needs high temperature for good yield or some form of activation. One of the simpler ways is to make 4-nitrophenyl ester of acid.
Another problem is that if you're mixing amine salt with amine, you're likely to get dynamic equilibrium with part of salt turning into base and base turning into salt. This depends of relative strengths of amines. Also amino acids are weaker as acids and harder to esterify, unless amine is bound into amide, like with Boc. This problem is also defeated with protecting groups.
Selection of appropriate protection of amino groups in peptides have following advantages. Generally reactions are performed by protecting amine groups .
a) It influences the purity and yield.
b) Suppress the racemisation and side reactions
All the best
The NH2 is more active with carboxylic acid to obtain an amide using DCC or BOP as coupling agents, in juste less than one hour at room temperature.
During the protection process both groups ( NH2 and COOH) will protect , but in different rates , so the product is a mixture of protected ( one or both site) and unprotected compound.
RNH2 should be more suitable as it has a lone pair in nitrogen of the -NH2 freely available to coordinate with COOH group of carbxylic actd.
Another two points have affect on the protection :
1- Type of the solvent protic or aprotic , and it's polarity.
2- The median, is it acidic or basic?
That is right primary amine is very active site , strong nuceophile.
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