Sciencemadness Discussion Board

it differences between diglyme and THF in LAH reaction

napoleon9 - 25-4-2011 at 08:25

when we made a reductive reaction by LiAlH4. We usually used THF solvent, but sometimes we used diglyme solvent. why ? when we used diglyme ? it differences between diglyme and THF in LAH reaction.

If you used triethylorthoformate protective group, how will you solution protective group ?


Picric-A - 26-4-2011 at 02:40

Diglyme is sometimes more favorable if a higher boiling point is required in reactions requiring more heat. THF is normally easier to use as extracting the product is easier due to ease of boiling off the THF.

Sandmeyer - 26-4-2011 at 12:58

Hmm... It is difficult to say, it is not clear what kind of functional group you want to reduce ;) As for protecting group, I think orthoester should be stable to LAH, but I didn't check the literature. I agree with Picric Acid on the boiling point, if your substrate requires forcing conditions then use diglyme but for LAH reductions in general I use THF as solvent, it has always worked.

EDIT: Generally speaking, you can take a look in Greene's Protective Groups in Organic Synthesis to see the compatibility of various protecting groups with various reagents. You can also check:

[Edited on 26-4-2011 by Sandmeyer]

napoleon9 - 29-4-2011 at 06:48

If product had OTHP group, I washed it by NaOH. But it will give Al(OH)3. So, product will be lost. Please give me some advices.
You will filtered or extracted it.

thanks everybody:D

Sandmeyer - 30-4-2011 at 12:30

Well, you will have to provide some more information, for examle draw a reaction scheme of what you are trying to accomplish :) and attach it as a picture, it is very difficult to discuss otherwise.

I'm puzzled why your THP ether is unstable to NaOH wash (if that's what you mean), it should be stable that's for sure, for more details see:

EDIT: I think I got it. ;) If you mean that after the reduction with LAH and consequent bad workup you're faced with a gel which you can't filter - "been there done that" :D - it is a problem so you have to be careful when quenching LAH, follow the well-established formula: for mixtures containing n grams of LAH, after the reaction, add n mL of H2O followed by n mL of 15% NaOH and finally then 3n mL of H2O. This will give you dry white granular precipitate which you can filter. There is also a method of after the reaction adding Na2SO4*10 H2O (solid) until "salts become white", I never tried this myself. As you have a THP ether, the acidic workup (with 10% H2SO4) will not be an option. I hope this helpz.

[Edited on 30-4-2011 by Sandmeyer]

napoleon9 - 30-4-2011 at 16:54

ok thanks
some magazine give me some advice was it washed by NaOH 0,1M with n mol NaOH = n LAH used.
how do you think about this procedure ?

when do you know finish reaction ? Do you see on TCL ? do you think different value Rf of alkyne and Rf of alkene ?

thank you:P

[Edited on 1-5-2011 by napoleon9]

untitled.JPG - 10kB

[Edited on 1-5-2011 by napoleon9]

Sandmeyer - 1-5-2011 at 07:50

There is a difference between wash and quench. What paper are you talking about? "Some magasine" means absolutely nothing. :D

Take a look in:

Insect Pheromones. Stereoselective Reduction of β- or ω-Alkynols to the Corresponding (E)-Alkenols by Lithium Tetrahydroaluminate

Authors: ROSSI, Renzo, CARPITA, Adriano

In: Synthesis 1977; 1977: 561-562

Read the method in the above paper, they use LAH and diglyme, just like you. Unfortunately I can't get the paper so I can't help you more. Take notice that, in general, LAH gives you E and catalytic hydrogenation Z alkene.

When you talk synthetic routes, papers, reactions and conditions provide as much information as you have otherwise it is very difficult to solve problems. ;)

napoleon9 - 12-5-2011 at 03:18

I were reduction of 2-(hex-1-yn-1-yl)-1,3-dioxolane by LiAlH4 in diglyme solution. After the reaction was finished, I had 2 ways to wash product:

1/ It washed by HCl 10% solution. After it was extracted with diethyl ether.
2/It was for x g of LAH x g of water, then 3x g of 15% KOH, then x g of water. But I didn't gain white solid. .....

Please give me some advices for this way!

It was moving protected group by HCl 15% for 1h, after it was extraxted by diethyl ether.


Sandmeyer - 13-5-2011 at 15:26

Post your entire experimental procedure, with all the juicy details in comprehensible English. You can translate Vietnamese to English online:|en|

Keep in mind that dilute acid will hydrolyse your protecting group.

The quench-formula you used is not the formula I suggested - no surprise you didn't get the white solid. If you have difficulty following this formula then try Na2SO4*10 H2O method I suggested earlier or get another job :P

napoleon9 - 15-5-2011 at 17:07

I were looking for a procedure :"The reaction was quenched by
addition of aqueous sodium hydroxide 0.1 mol/L (2 mL) at
0 °C followed by addition of ether (10 mL). The aqueous
layer was extracted twice with ether and the organic phase
was dried over anhydrous sodium sulphate. The product
was concentrated in vacuo and utilized in the next step
without further purification."

After this was hydrolysis protecting group procedure:
look below the picture :D

quocvu.bmp - 615kB

Some people were intruduce me that I could be hydrolysis protecting group procedure by CH3COOH 50%, reflux for 2 h.

can you give me some advice, please....

[Edited on 16-5-2011 by napoleon9]

vulture - 16-5-2011 at 14:26

For acid sensitive groups I usually work up LAH reductions with NH4Cl. Adding sulfate salts (MgSO4, Na2SO4) can also aid with precipitation of the gel.

But it seems that you are going to remove the protecting group in the next step anyway, so why don't you just use acidic workup?

napoleon9 - 19-5-2011 at 03:59

I will remove the protecting group in the next step. If you are me, how do you do ?

"I usually work up LAH reductions with NH4Cl. Adding sulfate salts (MgSO4, Na2SO4) can also aid with precipitation of the gel"

Can you give me this procedure ? Because I used workup LAH reductions with NH4Cl but It is gel. If you will filter it and wash it with ether, Could you do lost product ?

Hic, I am worry. Please give me some advice ? thanks everyone :(

vulture - 21-5-2011 at 14:58


I will remove the protecting group in the next step. If you are me, how do you do ?

Well then just do acidic workup with HCl, you'll get no gel and you're protecting group will be gone too, skipping the next step.