Help on organic synthesis

[vishesh]

Dear forum members

 

I am a biologist who is trying to synthesize an organic compound. I am trying to synthesize an organic compound 5-(2-hydroxy-5-nitrophenylazo)rhodanine using a protocol stated in article "Zaijun, L. et al. (2003). Analytical and Bioanalytical Chemistry 375, 408-413."

 

The protocol states that - Transfer 1.54 g of 4-nitro-2-aminophenol dissolved in 45 mL of 95% alcohol into a 100 mL beaker, add 12.0 mL of 6.0 mol L–1 HCI then cool the solution to 0 °C, and add 7 mL of 10% NaNO2 slowly. In another 200 mL beaker, 1.34 g of rhodanine and 14mL of 7.5 mol L–1 ammonia were added. After the solution has been cooled to 0 °C, add the above diazotized solution dropwise and leave the mixture overnight. The solution is then acidified to pH 1 with concentrated HCI and the precipitate was isolated and dried.

The crude product was re-crystallized from alcohol, giving pure 5-(2-hydroxy-5-nitrophenylazo)rhodanine (HNAR) in 65% yield.

 

When I acidify the reaction mixture I get yellow precipitate which are not soluble in ethanol. But when NaOH solution is added to these ppt. they solubelize just fine. According to authors this compound has three dissociation constants and it appears yellow in acidic conditions and red in basic conditions. As the compound has three states of pKa (2.75, 6.88, 10.91) can I precipitate this compound by using alkaline conditions? Also how can I check the purity of the compound formed?

 

Also I figured that this synthesis is a two step process which involves diazotization of 2-amino-4-nitrophenol followed by its addition to the solution of rhodanine. Can incomplete/inefficient diazotization be a problem in this synthesis? Is water essential for diazotization? Can I take conc. HCl or higher concentration of Sodium Nitrite to increase the efficiency of diazotization reaction?

 

Thanks.

[hypervalent_iodine]

I don't mean this to be rude, but I have to ask if you have much experience in synthetic organic chemistry and furthermore, if you have experience in handling sensitive compounds? Diazo aromatics are typically shock sensitive and will cause an explosion if you don't handle them correctly. Nitro aromatics will do the same. I'm happy to answer your questions here and will do in due course (I need to have a look at the paper), however I would like to er on the side of caution first and make sure you are fully aware and fully prepared for this kind of synthesis.

 

Also, you don't usually use beakers as reaction vessels, you would use round bottomed flasks. I haven't looked at the paper, but I am skeptical of the fact that it would specify the use of beakers.

Edited March 2, 2012 by hypervalent_iodine

[mississippichem]

I should stress that you DO keep that diazonation mixture cold. Do you stir vigorously during the diazonation? I ran into problems a few years back with cold diazonation mixtures forming gels.

[vishesh]

I don't mean this to be rude, but I have to ask if you have much experience in synthetic organic chemistry and furthermore, if you have experience in handling sensitive compounds? Diazo aromatics are typically shock sensitive and will cause an explosion if you don't handle them correctly. Nitro aromatics will do the same. I'm happy to answer your questions here and will do in due course (I need to have a look at the paper), however I would like to er on the side of caution first and make sure you are fully aware and fully prepared for this kind of synthesis.

 

Also, you don't usually use beakers as reaction vessels, you would use round bottomed flasks. I haven't looked at the paper, but I am skeptical of the fact that it would specify the use of beakers.

 

I am using RB flasks for synthesis and I am currently doing synthesis in a chemical hood. Protocol stated here is taken ad verbum from the paper. I also wear protective clothing and eye protection during synthesis. I have done some very basic functional group analysis in organic chemistry. So I don't have an experience in handling such compounds.

 

I should stress that you DO keep that diazonation mixture cold. Do you stir vigorously during the diazonation? I ran into problems a few years back with cold diazonation mixtures forming gels.

 

I keep mixture cold by keeping it in ice bath. Although I did not stirred the reaction mixture vigorously during diazonation. As soon as sodium nitrite is added to the mixture it forms a solid yellow colored precipitate. Also I am adding sodium nitrite very slowly to the reaction mixture.

Edited March 2, 2012 by vishesh

[hypervalent_iodine]

I'm having a little trouble accessing the proxy server for my university, so I'm unable to get the paper at the moment.

 

A few things at a glance.

 

• It would be called 2-amino-4-nitrophenol, not 4-nitro-2-aminophenol.
• By alcohol, I assume ethanol?
• How are you extracting the precipitate from the acidic mixture?

 

 

Also I figured that this synthesis is a two step process which involves diazotization of 2-amino-4-nitrophenol followed by its addition to the solution of rhodanine. Can incomplete/inefficient diazotization be a problem in this synthesis? Is water essential for diazotization? Can I take conc. HCl or higher concentration of Sodium Nitrite to increase the efficiency of diazotization reaction?

 

Thanks.

 

Are you monitoring your reaction with TLC? If so, and you should be, how does it look before you add it to the rhodanine solution? Obviously if the diazotization doesn't go to or near completion, you will get lower yields. As to whether the starting material messes with the second part to your synthesis, I'm not sure, but I doubt it.

 

At a guess, I would say that the precipitates you're getting when you acidify the solution could be ammonium salts. It would also explain why the precipitate is soluble when you basify it. I wouldn't precipitate under basic conditions, since you will pull through a bunch of impurities and starting material.

 

Are you asking whether or not you need to add water to participate in the reaction? If so, then no, but you will have water in the reaction whether you like it or not as it will form during the reaction and is of course in your HCl solution. Ignoring that, you would still want water as a solvent in this system as you need a solvent that is polar and can solubilise all of the charged complexes that are present in the reaction. Water is very good at that.

 

 

I would be careful with adding conc. HCl (in fact, I wouldn't do it at all) and the concentration of NaNO₂ should be kept as it is. If you are meaning that you want to add molar excess of the nitrite, I would also avoid that until you've played around with the reaction time. You need to be checking the progress of the reaction with TLC. Chances are, you aren't going to get it to work in the exact time frame stated in the paper.

 

Edit: Another thought regarding the addition of base. Generally not a good idea given that it might hydrolyse your rhodinane component.

Edited March 2, 2012 by hypervalent_iodine

[vishesh]

I'm having a little trouble accessing the proxy server for my university, so I'm unable to get the paper at the moment.

 

A few things at a glance.

 

• It would be called 2-amino-4-nitrophenol, not 4-nitro-2-aminophenol.
• By alcohol, I assume ethanol?
• How are you extracting the precipitate from the acidic mixture?

 

Are you monitoring your reaction with TLC? If so, and you should be, how does it look before you add it to the rhodanine solution? Obviously if the diazotization doesn't go to or near completion, you will get lower yields. As to whether the starting material messes with the second part to your synthesis, I'm not sure, but I doubt it.

 

At a guess, I would say that the precipitates you're getting when you acidify the solution could be ammonium salts. It would also explain why the precipitate is soluble when you basify it. I wouldn't precipitate under basic conditions, since you will pull through a bunch of impurities and starting material.

 

Are you asking whether or not you need to add water to participate in the reaction? If so, then no, but you will have water in the reaction whether you like it or not as it will form during the reaction and is of course in your HCl solution. Ignoring that, you would still want water as a solvent in this system as you need a solvent that is polar and can solubilise all of the charged complexes that are present in the reaction. Water is very good at that.

 

 

I would be careful with adding conc. HCl (in fact, I wouldn't do it at all) and the concentration of NaNO₂ should be kept as it is. If you are meaning that you want to add molar excess of the nitrite, I would also avoid that until you've played around with the reaction time. You need to be checking the progress of the reaction with TLC. Chances are, you aren't going to get it to work in the exact time frame stated in the paper.

 

Edit: Another thought regarding the addition of base. Generally not a good idea given that it might hydrolyse your rhodinane component.

 

 

Yes its 2-amino-4-nitrophenol and was wrongly mentioned in paper

 

I am using ethanol.

For extracting precipitate I am doing vacuum filtration.

 

I am not monitoring reaction progress using TLC.

 

Thanks for clearing many of my doubts. I guess I'll monitor my reaction using TLC next time and see if I can get complete diazotization and if that solves the problem. I'll come back to this forum if I face any problem during synthesis. Also I see a clear rationale about why I can not use basic conditions for precipitation.

 

Thanks a lot once again

[hypervalent_iodine]

No problems and certainly feel free to come back if you have any other questions.

 

Edit: Just re-read my last post and realised I had my stupid cap on. The precipitates won't be ammonium salts. Possibly the addition of HCl at the end is to generate ammonium salts, which will stay dissolved in your aqueous reaction mix, and allow your compound to crash out of solution. This way you keep out the impurities and starting material.

Edited March 2, 2012 by hypervalent_iodine