-----BEGIN PGP SIGNED MESSAGE----- Hash: SHA512 N-Propyl-nor-pentedrone (NPP) or α-propylaminopentiophenone synthesis - def 2025-09-23 +-----------------------------------------------------------------------------+ | | | M(NPP fb) = 219.32 g/mol M(2-bromo-valerophenone) = 241.124 g/mol | | M(NPP HCl) = 255.78 g/mol M(propylamine) = 59.11 g/mol | | | | M(HCl) = 36.46 g/mol | | M(Na2CO3) = 106 g/mol | | M(citric acid monohydrate) = 210.14 g/mol | | | +-----------------------------------------------------------------------------+ | | | n = m(2BrV) / M(2BrV) = 100g / 241.24g/mol = 0.415 mol | | | +-----------------------------------------------------------------------------+ | | | 1. Add 100g (76mL) 2BrV to a reaction flask with 250mL EtOAc (or xylene). | | | | 2. Add 62g (85mL) propylamine (2½ mol eq.) dropwise with vigorous stirring | | and maintaining temperature below < 45°C. | | | | 3. Run the reaction for +12h after the addition of the last drop. | | | | 4. Wash 2x with 100mL saturated NaHCO3 water. | | | | 5. Acidify with 15g HCl, that is, 45mL of 33% HCl(aq). | | | | 6. (Optional:) Wash the extracted aqueous layer with 100mL xylene. | | | | 7. Basify with 50g Na2CO3 - be careful with the released CO2 gas! | | | | 8. Decant the top freebase layer, discarding the bottom aqueous layer. | | | | 9. Dissolve the freebase into a freezing-cold acetone and acidify it with | | ~15.12g HCl (i.e., ~45.35g of 33% HCl(aq)) until the buffering capacity | | is exceeded and the pH becomes acidiic (pH < 7). | | | | Do not overshoot pH too low, although whether the crystallization is | | hindered by this remains unclear. | | | | Note that with cold acid and NPP freebase (straight out of freezer), it | | is likely that you will see visible crystals forming when introducing | | the acid. | | | | 10. Filter NPP crystals and wash repeatedly with cold acetone. If filtering | | is not possible due to poor precipitation, put the mixture in a freezer | | overnight (~12h or so) and try again. | | | | 11. Dry the NPP crystals thoroughly in a well-ventilated room with dry air. | | | | 12. (Optional): Recrystallize the product (in acetone or EtOH/H2O). | | | +-----------------------------------------------------------------------------+ | | | Theoretical yield: 106.15 g NPP HCl (0.415 mol). | | Actual yield: ? | | | +-----------------------------------------------------------------------------+ | | | In step 5, you can also use 90g citric acid monohydrate (dissolved in 150mL | | of H2O). However, citric acid is a triprotic acid so you'll need in step 7 | | ~3.5 mol eq. of Na2CO3 (150g or so). | | | +-----------------------------------------------------------------------------+ -----BEGIN PGP SIGNATURE----- iHUEARYKAB0WIQRRfNzxkhGCNUJHauoZ/qATiDeBBAUCaNJxdgAKCRAZ/qATiDeB BLEaAP9RK+Yo9L6ebUOXqT2EPhC9/9NkuVsIiwQy8DcqtFD4CwD/VJ5zVU3gMcVh hbfh8kMO+zcbuLrPfr7jJhreaSpcEQ0= =1TUg -----END PGP SIGNATURE-----