Hi, I'd like to post the improvements I made for this synthesis:
For oxime synthesis, 40 hours is just insane, you can do it in just 2 hours :
10g helional + 15.35g sodium acetate tetrahydrate (or 8.16g anhydrous) + 3.88g NH3OHCl in 50mL water and 50mL EtOH. Reflux 2h. Extract 3 times 20mL DCM (You can dilute the Rm if the DCM forms an emulsion due to the ethanol) and wash the organic phase twice with 50mL water. The DCM extracts are dried using Na2SO4 and then evaporated at 110°C. You will see that the Rm becomes pink after 10min, then yellow after 30min. You'll get almost quantitative yields (96% here).
Oxime, even when vacuum-dried, is a pain in the ass to crystallize. I'd therefore advise you to use it in its “oil” form for the Beckmann rearrangement, as it makes no difference. The oil is quite viscous, so I'd advise you to heat it when you want to transfer it to another glassware. As it heats up, it becomes much less viscous.
For Beckmann, the reason GhostChemist uses so much DCM is that the amide is not very soluble in DCM. In fact, in the publication, they use DCM to triturate the amide. My advice would be to let cool the Rm, and when the brown amide precipitates, just filter it out, and recrystallize the amide in heptane, toluene or xylene (any apolar solvent with a high b.p.). When cold, apolar solvent solubilizes very badly the amide, so if you give the Rm enough time to cool down after the Beckmann rearrangement, you won't have any loss.
Also, as long as the reaction is green, it's not complete. It will start to turn light/dark brown when it's finished.
For oxime synthesis, 40 hours is just insane, you can do it in just 2 hours :
10g helional + 15.35g sodium acetate tetrahydrate (or 8.16g anhydrous) + 3.88g NH3OHCl in 50mL water and 50mL EtOH. Reflux 2h. Extract 3 times 20mL DCM (You can dilute the Rm if the DCM forms an emulsion due to the ethanol) and wash the organic phase twice with 50mL water. The DCM extracts are dried using Na2SO4 and then evaporated at 110°C. You will see that the Rm becomes pink after 10min, then yellow after 30min. You'll get almost quantitative yields (96% here).
Oxime, even when vacuum-dried, is a pain in the ass to crystallize. I'd therefore advise you to use it in its “oil” form for the Beckmann rearrangement, as it makes no difference. The oil is quite viscous, so I'd advise you to heat it when you want to transfer it to another glassware. As it heats up, it becomes much less viscous.
For Beckmann, the reason GhostChemist uses so much DCM is that the amide is not very soluble in DCM. In fact, in the publication, they use DCM to triturate the amide. My advice would be to let cool the Rm, and when the brown amide precipitates, just filter it out, and recrystallize the amide in heptane, toluene or xylene (any apolar solvent with a high b.p.). When cold, apolar solvent solubilizes very badly the amide, so if you give the Rm enough time to cool down after the Beckmann rearrangement, you won't have any loss.
Also, as long as the reaction is green, it's not complete. It will start to turn light/dark brown when it's finished.
hydroxylamine can even be simply synthesis OTC with good yields:
(You can skip the formaldehyde part if you don't have any, that works just as well).
(You can skip the formaldehyde part if you don't have any, that works just as well).
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Your reaction takes longer because you're doing it at R°t and not at reflux. If we take the rule of thumb: reaction rates for many reactions double for every ten degrees Celsius increase in temperature, which means that my reaction takes place about 32 to 64 times faster than at R°t. Moreover, most protocols, such as for vanilin, suggest only 20 min at reflux to complete the reaction.
Even for large-scale applications, this is sufficient; for example, p-Hydroxyphenylacetaldehyde Oxime is produced in just 6h at R°t. The maximum time I've been able to find for oxime synthesis is for caprolactam, 12h at 100°C. So even though scaling up may take longer, I'm sure you can form your oxime in less than 12h if you heat at reflux, and not in 40 hours, unless there's an interest in doing the reaction at R°t, in which case I'm interested to know why.
Even for large-scale applications, this is sufficient; for example, p-Hydroxyphenylacetaldehyde Oxime is produced in just 6h at R°t. The maximum time I've been able to find for oxime synthesis is for caprolactam, 12h at 100°C. So even though scaling up may take longer, I'm sure you can form your oxime in less than 12h if you heat at reflux, and not in 40 hours, unless there's an interest in doing the reaction at R°t, in which case I'm interested to know why.
I'm sure it works because the reaction rate depends on the concentration and not on the volume, whether you're on a small scale or a large scale the concentration remains the same, your reaction will take 3 hours whether you're handling mmol or moles, otherwise industrial processes would take months.
en.wikipedia.org
Reaction rate - Wikipedia
Your reaction lasts 40h because you do it at R°t, do a reflux set-up and you will also finish it in 2h-3h.