Hello,
i found this synthesis but it seems a bit to simple is it correct or not and if correct what would the theoratical yield be?
Materials and Reagents
Phenyl2propanone (P2P): ~130 ml (approximate scale based on 2000 ml flask volume)
Sodium borohydride (NaBH4): ~1520 g (stoichiometric excess, see calculation below)
Methanol or ethanol (anhydrous preferred): ~1000 - 1500 ml (solvent for reduction)
Dilute hydrochloric acid (e.g., 1 M HCl): for quenching and salt formation
Dichloromethane (DCM) or diethyl ether: ~1000 ml (for extraction)
Anhydrous sodium sulfate: for drying organic layer
Ice and water: for cooling and quenching
Stepbystep Synthesis
1. Setup:
Place the 2000 ml roundbottom flask on a magnetic stirrer. Insert a stir bar.
Add approximately 130 ml of phenyl-2-propanone to the flask.
Add 1000-1500 ml of anhydrous methanol or ethanol to dissolve the P2P completely.
2. Cooling:
Place the reaction flask in an ice bath to maintain the temperature at 05 °C. Insert a thermometer to monitor temperature.
3. Preparation of NaBH4 solution:
Weigh approximately 1520 g of sodium borohydride (about 1.5 equivalents relative to P2P).
Optionally, dissolve NaBH4 in a small amount of cold methanol or add as solid directly.
4. Addition of NaBH4:
Add the sodium borohydride portionwise slowly to the cooled reaction mixture over 2030 minutes while stirring.
Maintain temperature at 05 °C to control reaction rate and minimize side reactions.
5. Reaction time:
Once addition is complete, stir the mixture at 05 °C for an additional 12 hours.
Optionally, allow the reaction to warm to room temperature and stir for another hour to ensure completion.
6. Quenching:
Carefully add dilute hydrochloric acid (1 M HCl) dropwise to quench excess NaBH4 and protonate the amine intermediate.
Monitor pH to reach acidic conditions (pH ~2-3).
7. Extraction:
Transfer the reaction mixture to a separatory funnel.
Extract the product with ~3 × 300 ml portions of dichloromethane (DCM) or diethyl ether.
Combine organic layers.
8. Washing and drying:
Wash the combined organic extracts with water (2 × 200 ml).
Dry the organic layer over anhydrous sodium sulfate (approx. 50100 g).
Filter to remove drying agent.
9. Concentration:
Evaporate the solvent under reduced pressure using a rotary evaporator to yield crude AMP free base as an oil or solid.
10. Salt formation (optional):
Dissolve the crude AMP free base in minimal acetone or ethanol (~100 ml).
Slowly add 35 ml of concentrated sulfuric acid dropwise with stirring until neutral pH is reached and a precipitate forms.
Filter the AMP sulfate salt by vacuum filtration and dry under vacuum.
Steam distillation can be used to isolate and partially purify AMP freebase, especially to separate it from highboiling impurities. However, steam distillation often does not provide the high purity required for freebase AMP due to possible codistillation of impurities and limited separation efficiency.
For higher purity, ShortPath vacuum distillation is preferred because:
It allows distillation at lower temperatures, minimizing decomposition.
It provides better separation and higher purity by controlling pressure and temperature precisely.
It removes residual solvents and impurities effectively.
In summary:
Steam distillation can be a preliminary purification step.
For high purity freebase AMP, shortpath vacuum distillation is generally necessary.
Theoratical Yield:
Molecular weight of P2P: 134.18 g/mol
Molecular weight of AMP freebase: approximately 135.21 g/mol
Therefore, from 1 mole of P2P (134.18 g), the theoretical maximum yield of AMP freebase is approximately 135.21 g.
Summary:
Theoretical yield (g AMP) = grams of P2P × (135.21 / 134.18) ≈ grams of P2P × 1.0077
Practically, almost a 1:1 mass yield is expected under ideal conditions.
i found this synthesis but it seems a bit to simple is it correct or not and if correct what would the theoratical yield be?
Materials and Reagents
Phenyl2propanone (P2P): ~130 ml (approximate scale based on 2000 ml flask volume)
Sodium borohydride (NaBH4): ~1520 g (stoichiometric excess, see calculation below)
Methanol or ethanol (anhydrous preferred): ~1000 - 1500 ml (solvent for reduction)
Dilute hydrochloric acid (e.g., 1 M HCl): for quenching and salt formation
Dichloromethane (DCM) or diethyl ether: ~1000 ml (for extraction)
Anhydrous sodium sulfate: for drying organic layer
Ice and water: for cooling and quenching
Stepbystep Synthesis
1. Setup:
Place the 2000 ml roundbottom flask on a magnetic stirrer. Insert a stir bar.
Add approximately 130 ml of phenyl-2-propanone to the flask.
Add 1000-1500 ml of anhydrous methanol or ethanol to dissolve the P2P completely.
2. Cooling:
Place the reaction flask in an ice bath to maintain the temperature at 05 °C. Insert a thermometer to monitor temperature.
3. Preparation of NaBH4 solution:
Weigh approximately 1520 g of sodium borohydride (about 1.5 equivalents relative to P2P).
Optionally, dissolve NaBH4 in a small amount of cold methanol or add as solid directly.
4. Addition of NaBH4:
Add the sodium borohydride portionwise slowly to the cooled reaction mixture over 2030 minutes while stirring.
Maintain temperature at 05 °C to control reaction rate and minimize side reactions.
5. Reaction time:
Once addition is complete, stir the mixture at 05 °C for an additional 12 hours.
Optionally, allow the reaction to warm to room temperature and stir for another hour to ensure completion.
6. Quenching:
Carefully add dilute hydrochloric acid (1 M HCl) dropwise to quench excess NaBH4 and protonate the amine intermediate.
Monitor pH to reach acidic conditions (pH ~2-3).
7. Extraction:
Transfer the reaction mixture to a separatory funnel.
Extract the product with ~3 × 300 ml portions of dichloromethane (DCM) or diethyl ether.
Combine organic layers.
8. Washing and drying:
Wash the combined organic extracts with water (2 × 200 ml).
Dry the organic layer over anhydrous sodium sulfate (approx. 50100 g).
Filter to remove drying agent.
9. Concentration:
Evaporate the solvent under reduced pressure using a rotary evaporator to yield crude AMP free base as an oil or solid.
10. Salt formation (optional):
Dissolve the crude AMP free base in minimal acetone or ethanol (~100 ml).
Slowly add 35 ml of concentrated sulfuric acid dropwise with stirring until neutral pH is reached and a precipitate forms.
Filter the AMP sulfate salt by vacuum filtration and dry under vacuum.
Steam distillation can be used to isolate and partially purify AMP freebase, especially to separate it from highboiling impurities. However, steam distillation often does not provide the high purity required for freebase AMP due to possible codistillation of impurities and limited separation efficiency.
For higher purity, ShortPath vacuum distillation is preferred because:
It allows distillation at lower temperatures, minimizing decomposition.
It provides better separation and higher purity by controlling pressure and temperature precisely.
It removes residual solvents and impurities effectively.
In summary:
Steam distillation can be a preliminary purification step.
For high purity freebase AMP, shortpath vacuum distillation is generally necessary.
Theoratical Yield:
Molecular weight of P2P: 134.18 g/mol
Molecular weight of AMP freebase: approximately 135.21 g/mol
Therefore, from 1 mole of P2P (134.18 g), the theoretical maximum yield of AMP freebase is approximately 135.21 g.
Summary:
Theoretical yield (g AMP) = grams of P2P × (135.21 / 134.18) ≈ grams of P2P × 1.0077
Practically, almost a 1:1 mass yield is expected under ideal conditions.
