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Request for help in reaction between acyl halide and amine
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Request for help in reaction between acyl halide and amine
The ideal is of course that all components in a reaction are in solution, but this doesn't always happen. I wouldn't use water in general around an acid chloride, so try first using DMF and just see if enough of the amino goes into solution to allow the reaction to proceed. You might have to heat/sonicate the reaction a bit, but more than likely it will proceed (admittedly slowly) as long as you don't get decomposition. Other solvents can be used as well, but generally stay away from protic solvents.
The ideal is of course that all components in a reaction are in solution, but this doesn't always happen. I wouldn't use water in general around an acid chloride, so try first using DMF and just see if enough of the amino goes into solution to allow the reaction to proceed. You might have to heat/sonicate the reaction a bit, but more than likely it will proceed (admittedly slowly) as long as you don't get decomposition. Other solvents can be used as well, but generally stay away from protic solvents.
A simple solution would be to avoid the use of the acid chloride altogether. You should be able to use EDCI/triethylamine/NHS plus your amine in DMF at room temperature. I've used these conditions to conjugate taurine with a DMF-soluble carboxylic acid and it worked well enough (>60%) If you still want to use the acid chloride in DMF (check that there are no reactions between acid chloride and DMF) it should be possible to enhance the solubility of the amine in DMF by adding an equivalent of a tertiary amine (triethylamine, diisopropylethylamine, etc.). I usually add 2-4x equivalents of tertiary amine to ensure that the HCl released during the coupling is scavenged.
A simple solution would be to avoid the use of the acid chloride altogether. You should be able to use EDCI/triethylamine/NHS plus your amine in DMF at room temperature. I've used these conditions to conjugate taurine with a DMF-soluble carboxylic acid and it worked well enough (>60%) If you still want to use the acid chloride in DMF (check that there are no reactions between acid chloride and DMF) it should be possible to enhance the solubility of the amine in DMF by adding an equivalent of a tertiary amine (triethylamine, diisopropylethylamine, etc.). I usually add 2-4x equivalents of tertiary amine to ensure that the HCl released during the coupling is scavenged.
I wouldn't use water in general around an acid chloride, so try first using DMF and just see if enough of the amino goes into solution to allow the reaction to proceed. You might have to heat/sonicate the reaction a bit, but more than likely it will proceed (admittedly slowly) as long as you don't get decomposition.
Other solvents can be used as well, but generally stay away from protic solvents.
I wouldn't use water in general around an acid chloride, so try first using DMF and just see if enough of the amino goes into solution to allow the reaction to proceed. You might have to heat/sonicate the reaction a bit, but more than likely it will proceed (admittedly slowly) as long as you don't get decomposition.
Other solvents can be used as well, but generally stay away from protic solvents.
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If you still want to use the acid chloride in DMF (check that there are no reactions between acid chloride and DMF) it should be possible to enhance the solubility of the amine in DMF by adding an equivalent of a tertiary amine (triethylamine, diisopropylethylamine, etc.). I usually add 2-4x equivalents of tertiary amine to ensure that the HCl released during the coupling is scavenged.
If you still want to use the acid chloride in DMF (check that there are no reactions between acid chloride and DMF) it should be possible to enhance the solubility of the amine in DMF by adding an equivalent of a tertiary amine (triethylamine, diisopropylethylamine, etc.). I usually add 2-4x equivalents of tertiary amine to ensure that the HCl released during the coupling is scavenged.
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