A few wasps have contacted Ab2 asking for details of the acetylation step used in a DET synth. Ab2 thought it made sense to post it to the forum so other wasps can avail themselves of this OTC shortcut to an acetylated product.
Ab2 should also mention that her experiments using aspirin where inspired by a thread over at Science madness (https://www.sciencemadness.org/whisper/viewthread.php?tid=11706#pid149377) where Jor was acetylating aniline with asprin. However, this was some time ago and it received little attention at the time. There are also many references in literature for the in-vivo acetylation of prostaglandin synthase with acetylsalicylic acid. This is also very handy technique to remove 1° and 2° amines from mixtures of 3° amines, and can be done directly to the post rxn residue of an alkyl halide n-alkylation after the solvent and DIPEA have been removed by distillation. Ab2 is sure enterprising wasps can think of a myriad of other applications for it too.
This method is simple, clean and fast.
Dissolve a 1.2 molar XS of aspirin1 (relative to tryptamine) in the minimum amount of boiling EtOH (other alcohols like IPA or MeOH will also work, but solubilities will vary). Some of the binders will not go into solution, but it doesn’t matter, they will not affect the rxn. Dissolve the tryptamine in the minimum amount of boiling EtAcO or EtOH2. Remove from heat and let both stand long enough to cool by 1-2 degrees, then combine the two mixtures and heat to boiling again for 1-2 minutes. Remove from heat and allow to cool to room temp3, then refrigerate for 20 minutes. Upon refrigeration long thin needles may form in the post rxn mixture if you didn’t add too much solvent. This is a good sign. Neutralize, basify and extract using EtAcO. (Or simply separate the layers, retaining the organic layer, if you used EtAcO as your rxn solvent)
That’s it, you’re done.
1. acetylsalicylic acid 180 g/mol, tryptamine 160 g/mol
2. Tryptamine is more soluble in EtAcO than in EtOH, although it is soluble in both.
3. You can follow this RXN on TLC. Using a 3/1 EtAcO/MeOH your tryptamine will have an rf of 0.1 – 0.2, while your n-acetyl tryptamine will have an rf of 0.6 - 0.7.
Ab2 should also mention that her experiments using aspirin where inspired by a thread over at Science madness (https://www.sciencemadness.org/whisper/viewthread.php?tid=11706#pid149377) where Jor was acetylating aniline with asprin. However, this was some time ago and it received little attention at the time. There are also many references in literature for the in-vivo acetylation of prostaglandin synthase with acetylsalicylic acid. This is also very handy technique to remove 1° and 2° amines from mixtures of 3° amines, and can be done directly to the post rxn residue of an alkyl halide n-alkylation after the solvent and DIPEA have been removed by distillation. Ab2 is sure enterprising wasps can think of a myriad of other applications for it too.
This method is simple, clean and fast.
Dissolve a 1.2 molar XS of aspirin1 (relative to tryptamine) in the minimum amount of boiling EtOH (other alcohols like IPA or MeOH will also work, but solubilities will vary). Some of the binders will not go into solution, but it doesn’t matter, they will not affect the rxn. Dissolve the tryptamine in the minimum amount of boiling EtAcO or EtOH2. Remove from heat and let both stand long enough to cool by 1-2 degrees, then combine the two mixtures and heat to boiling again for 1-2 minutes. Remove from heat and allow to cool to room temp3, then refrigerate for 20 minutes. Upon refrigeration long thin needles may form in the post rxn mixture if you didn’t add too much solvent. This is a good sign. Neutralize, basify and extract using EtAcO. (Or simply separate the layers, retaining the organic layer, if you used EtAcO as your rxn solvent)
That’s it, you’re done.
1. acetylsalicylic acid 180 g/mol, tryptamine 160 g/mol
2. Tryptamine is more soluble in EtAcO than in EtOH, although it is soluble in both.
3. You can follow this RXN on TLC. Using a 3/1 EtAcO/MeOH your tryptamine will have an rf of 0.1 – 0.2, while your n-acetyl tryptamine will have an rf of 0.6 - 0.7.