[donaxad704]

Hi, so I want to try out the following synthesis but I am still unsure about a few things as the guide I found is a little imprecise at some steps:

The main two ingredients are Benzaldehyde-2,4-disulfonic acid disodium salt (http://www.chemspider.com/Chemical-Structure.148249.html?rid=eab8f5d0-39fd-4fec-b59c-18761b05cc83&page_num=0) and N-tert-butylhydroxylamine (http://www.chemspider.com/Chemical-Structure.89031.html?rid=98327942-127b-429f-aa0f-9a68e58f1cb0). These two molecules should react in a condensation to Disufenton sodium (http://www.chemspider.com/Chemical-Structure.4944488.html?rid=8eb8acfa-fc26-49fa-bca0-960eeef76b2b)

The steps of the reaction are according to the source I found the following:

• A 3-neck 250ml round bottom flask was setup with a stir bar, a gas dispersion tube, an addition funnel and a Friedrichs condenser cooled with recirculating ice.
• To the flask were added 200 mL of methanol, Benzaldehyde-2,4-disulfonic acid disodium salt (9.31g, 30mmoles) and N-tert-butylhydroxylamine (2.67g, 30mmoles - already dissolved in 25ml of methanol).
• The reaction was heated to reflux with a heating mantle while bubbling the reaction with nitrogen with stirring.
• The mixture was refluxed for 2 hours.
• An additional 30mmol of N-tert-butylhydroxylamine was added.
• Refluxing was continued with nitrogen bubbling for at least 18 hours but no more than 24 hours.
• The hot mixture was filtered on a Buchner funnel and the solid washed with hot methanol.
• The methanol was stripped off by rotary evaporation to a yellow viscous oil.
• Hot 1:1 ethanol:acetone (200mL) was added and the mixture heated to dissolve the oil.
• The solution was cooled to crystallise the product.
• The product was collected on a Buchner funnel and dried under vacuum overnight.
• The reaction typicaly gives 75% yield of Disufenton sodium, a white powder.

Several aspects of this guide are still unclear to me:

• In this guide, the exact temperature for the condensation is not given. Obviously there is an upper limit due to the evaporation point of methanol. However I do not know the disintegration temperature for the 2 precursors in this reaction. The melting point for N-tert-buytlhydroxylamine is supposed to be at 64°C and the boiling point at 120.9ºC at 760mmHg. However I am still worried, that the compound may disintegrate already at lower temperatures slowly. The same applies also to the other precursor, which is supposed to melt at 83°C and most importantly to the final product for which I have no clue at which temperature it disintegrates (which it definetely does). Can somebody give me advice which temperature for the synthesis is most suitable and/or how to find this out?
• As far as I understand the nitrogen is just there to create an atmosphere void of oxygen (to avoid oxidative reactions). Does this mean, that one only needs to produce a slight constant nitrogen flow after initially removing all the previous air so that no new air from the outside enteres the flask? Or is in the reaction in fact oxygen constantly produced as a side product, which needs to be washed out by the nitrogen? Also does one really need to bubble the nitrogen into the solvent or does it suffice if one simply 'fills' the flask with it?
• To my understanding the molar amount of N-tert-butylhydroxylamine is twice the one of the Benzaldehyde-2,4-disulfonic acid disodium salt as the condensation also creates water as a side product. I believe that N-tert-butylhydroxylamine strongly reacts with water and hence one also needs twice the amount of N-tert-butylhydroxylamine in order to completely deplete the other precursor in this reaction. However I do not know what the product of the reaction of N-tert-butylhydroxylamine with water will be. Can somebody maybe explain me what the additional side products of this reaction can be?
• I understand step 7. in the way, that the filter is there to filter out solid impurities after the reaction while the actual desired output is actually the solution which has passed the filter. I guess I am correct with this assumption?
  
• Since the condensation already takes almost an entire day I thought about putting the resulting solution in a refrigerator to avoid degradation of the product and do the evaporation of the methanol in the rotary evaporator maybe a few hours (maybe 6) later. Is it reasonable to believe, that this will not degrade the product?
  
• For the rotary evaporator I have the same question as for the reaction itself. I think 40 degrees should be a good temperature while the evaporation is mainly accomplished by reducing the pressure inside the rotary evaporator steadily.
• Is the total volume of the solvent used for crystallisation 200ml (i.e. 100ml of ethanol and 00ml of acetone), or in fact 400ml?
  
• What is the best way to proceed the crystallisation in detail.
  
• Generally speaking: what is the temperature which I should see as upper boundary in every part of the this synthesis?
  

Already many thanks in advance!

[Babcock_Hall]

I read your questions, and I doubt that you have sufficient training to perform this synthesis safely and successfully on your own.  If you are a student, maybe you should do supervised chemical research under a professor.  Why did you pick this synthesis and not something a bit easier?