[jimmyapex]

Hello,everybody,could anyone help me choose an appropriate reducing agent to reduce acid/ester to alcohol while keeping nitro group not being reduced?

The final product i wanna synthesis is 1-bromo-3-(4-nitrophenyl)propane.I searched the Beilstein database and the most routes are started from 1-bromo-3-phenyl propane and just need a nitration step.In order to remove 2-isomer of nitration,we must do distillation under high vacuum at about 0.13 torr,and the purification of 4-isomer should be handled  at negative 65 degree centigrade as it is liquid with low melting point.The above reaction condition is somewhat hard for us to meet in my laboratory.As a result,i'm going to try another route which start from 4-(4-nitrophenyl)butanoic acid which i can get.So, i need a good reducing agent to reduce carboxylic acid to alcohol and then do bromation,but the nitro group might be reduced at the same time. Can anyone give any suggestion?

If u could find a good reducing agent or a good reaction condition or you can figure out any other good synthesis route,please let me know.Thanks a lot in advance.

[agrobert]

Your naming is off I don't know if you want a three or four carbon chain because you go from butanoic acid to propane.

[macman104]

Hi, I've actually done this reaction before.  Unfortunately, I'm a couple hundred miles away from the lab I work in, and so I can't provide exact details.

However, I do know that while it can be long and use quite a bit of solvent, careful column chromatography instead of the the distillation under reduced pressure can yield pure para-nitro product.  I want to say I started with 1:12 ethyl acetate/hexane mixture (but I'm not 100% on the mixture, it may have been 1:10), and just wash with that until all of the ortho product is gone, and then you are free to rinse with ethyl acetate and get pure para product.  In the middle there will be some o/p mixture, but it should be minimal.

I'm not sure about the reduction, but I thought I would mention the other possibility...

[jimmyapex]

sorry for my mistake in typing,it's propyl acid not butanoic acid.

[jimmyapex]

thanks for your suggestion,macman104!I think going through flash culumn might takes too much time.I'll try.

[lutesium]

NaBH4 might work maybe... But I don't know if the media isn't acidic enough to catch a fire!!! Maybe you can neutralize your acid (w/Na2CO3) first and then start the reducing process...

Good luck with your study


Lutesium...

[macman104]

thanks for your suggestion,macman104!I think going through flash culumn might takes too much time.I'll try.

It does take a decent amount of time (definitely need to devote an evenings worth to it), but right now it's the best solution we have.  However, if you are able to find a suitable alternative, I'd love to hear about it.

[gaurang]

Ester and acid is only reduced by LiAlH4 and Red-AL solution.

[jimmyapex]

After studying the synthesis routes and procedures,I’d like to let you know of my plans for synthesizing p-nitrophenylpropyl bromide.

I’d like to use phenylpropyl alcohol as starting material and do bromation at the first step. However,it’s somewhat difficult to get pure 4-nitrophenylpropyl bromide as it’ll give ortho-nitro isomer during the reaction and it has to be removed by distillation at high temperature under high vacuum.(130-136 degree/0.4 torr, 156-160/2torr) as the literature indicates. Also, It might be dangerous to heat the compound with nitro-group at high temperature. Good thing, the melting point of this compound is about negative 2 to 0 degree as the literature reports,so,I’ll try to do recrystalization to remove the ortho-nitro isomer to seek the possibility. In addition, I’ve been told that the ortho-nitro isomer could be removed by distillation with water. The last possible way is by passing through silica gel column as macman104 suggests. I’ll try to do the purification based on the above mentioned tree possible methods to see which will be the most effective.

If all the above measures are proved to be unfeasible, I think I’ll change the synthesis route and start with p-nitrophenyl propyl acid.The first step is esterification to give p-nitrophenyl propyl acid methyl ester and then reducing the ester to alcohol while keeping the nitro-group not being reduced at the second step. The NaBH4 and LiAlH4 could be used as the reducing agent as the attached articles reported. The final step is bromation to give target compound.

I’ve bought phenylpropyl alcohol today and I estimate I can get it in the next few days. I’ll try to synthesis the compound according to above measures and I’ll keep you informed if I get any update. Welcome to take part in the discussion of this topic and thanks for your attention and help.

[jimmyapex]

attached is the third article

[macman104]

I look forward to hearing how the recrystallization and the distillation go, please do keep us informed (or at least me ).

[Rabn]

yes, please do post your results.

[PAY]

It shoud be better to start with 4 -nitrophenylbutanoic acid. You might to transform it in necessary product by Hunsdiker reaction, or Barton reaction/