Sciencemadness Discussion Board

Yield of Nencki reaction

goldberg - 20-3-2021 at 04:22

Have you any practical experience with Nencki reaction?
I tried to synthesise gallacetophenone following this procedure but on much smaller scale (i have used 15g of pyrogallol) http://www.orgsyn.org/demo.aspx?prep=CV3P0761
but my yield was about 20%.
Reaction was carried out in 100ml beaker heated on electric plate and manually stirred while keeping temperature below 150C for 20min.
Refluxing of zinc chloride, glacial acetic acid and pyrogallol for 1h also did not gave better results.

I have also tried using hydroquinone to get quinacetophenone but yield was about 15%.

I'm thinking what i have missed? After reaction mixture was poured into brine and putted into refrigerator, then i have collected crystals and recrystalized them from 20% ethanol with activated carbon.

Significant amount of red water soluble substance have formed in both cases so maybe temperature was too high?

njl - 20-3-2021 at 06:20

Did you use acetic anhydride or not?

goldberg - 20-3-2021 at 08:56

No, i have not used acetic anhydride. Only glacial acetic acid and anhydrous zinc chloride.
I'm thinking about making next attempt but with lower temperature, around 140C.
Red colored by-product appears immediately after addition of pyrogallol or hydroquinone to hot solution of zinc chloride in acetic acid.

DraconicAcid - 20-3-2021 at 12:02

I suspect acetic anhydride would give you an ester.

njl - 20-3-2021 at 13:50

I'm sure it would as a side reaction, but the procedure linked uses acetic anhydride, and it looks like it's not even catalytic. So goldberg if you left out acetic anhydride there really isn't any mystery here. Looking at the mechanism, I think you need an anhydride.

DraconicAcid - 20-3-2021 at 13:56

"One hundred and sixty-five grams (1.2 moles) of anhydrous zinc chloride (Note 1) is dissolved with the aid of heat in 165 g. (158 ml., 2.7 moles) of glacial acetic acid, which has been placed in a 1-l. beaker. To this hot mixture (about 140°), 110 g. (1 mole) of resorcinol is added with constant stirring."

No, no acetic anhydride.

njl - 20-3-2021 at 15:05

Ok, this is weird. I was sure @goldberg linked the following prep (which actually is about gallacetophenone)

http://orgsyn.org/demo.aspx?prep=CV2P0304

But now the link leads to the prep for resacetophenone. Even though it doesn't show up as edited. Anyway, the prep for gallacetophenone calls for acetic anhydride.

[Edited on 3-20-2021 by njl]

DraconicAcid - 20-3-2021 at 15:06

Okay- I thought I was going blind and was wondering where you had seen acetic anhydride. All good, and I stand corrected.

UC235 - 20-3-2021 at 15:10

You could start by using the orgsyn procedure for your target compound (which does use acetic anhydride): http://orgsyn.org/demo.aspx?prep=CV2P0304

That procedure calls for 140-145C for 45min.

It may be that the acetic anhydride is not strictly necessary but it consumes water liberated in the course of the reaction. The quality of your acetic acid may be an issue and ZnCl2 is extremely hygroscopic. Refluxing everything prior to adding the pyrogallol will conveniently dry everything thoroughly if acetic anhydride is being used.

goldberg - 21-3-2021 at 03:28

Unfortunately acetic anhydrite has a few bad uses and due to this it is controlled substance. That's why i do not want to try obtain it.
How about using Al2O3 or molecular sieves for removal of water?
Idea with refluxing everything befor adding pyrogallol is interesting but condenser has te be well choosen to let water escape why condensing acetic acid.

But even with procedure without acetic anhydrie yield was much better than what i get.
How water sensitive this reaction is? Maybe i should dry ZnCl2 immediately before use.

Gave you any experience with workup and recrystallisation of gallacetophenone and quinacetophenone?
Maybe during this phase i lost much of product.

njl - 21-3-2021 at 07:19

Try a regular fischer esterificaton followed by a fries rearrangement. This route will have lower selectivity but you only need the you already have, plus some H2SO4. I believe ZnCl2 works for the fries but AlCl3 is better.

solo - 21-3-2021 at 10:13


Reference Information



Synthesis of Gallacetophenone (2,3,4-trihydroxyacetophenone)

Procedure

In a 250mL RB flask, fitted with a reflux condenser to which is attached a calcium chloride tube, 28g (0.21 mole) of freshly fused and finely powdered zinc chloride (Note 1) is dissolved in 38mL of glacial acetic acid by heating in an oil bath at 135–140°C. Forty grams (0.37 mole) of 95% acetic anhydride is then added to the clear, pale brown liquid, followed by the addition in one lot of 50g (0.4 mole) of distilled pyrogallol (Note 2). The mixture is heated at 140–145°C (Note 3) for 45 minutes with frequent and vigorous shaking. The unused acetic anhydride and acetic acid are removed by distilling under reduced pressure. The red-brown cake is broken up by the addition of 300mL of water with mechanical stirring for a few minutes. The mixture is cooled in ice water, filtered with suction, and washed with cold water. The crude material, 45–50g, is crystallized from 500mL of boiling water saturated with sulfur dioxide. The yield of straw-colored needles melting at 171–172°C is 36–38g (54–57% of the theoretical amount). On saturating the mother liquor with salt and cooling to 10°C, 4–5g of crude material is obtained, which on recrystallization yields 3–4g of pure material (Note 4).


....see,

https://chemistry.mdma.ch/hiveboard/novel/000413969.html

[Edited on 21-3-2021 by solo]

[Edited on 21-3-2021 by solo]

zed - 21-3-2021 at 14:20

Well, it appears you are running it as a Friedel-Crafts, which you might not have to do.

The Acetyl esters, and Allyl Ethers of Phenols, rearrange pretty easily, and in high yields.

Generally, the group goes Ortho, but if Ortho isn't available, migration will be Para.

Kind of a special case. Works for Acetyl. Works for Allyl. Other groups may be hideously transmogrified by the process. Like in the horror movie "The Fly".

I'll go check for a reference.

OK, I'm back.

Ummm. Perhaps I am mistaken.

Seems like the same reaction to me. Acetyl and Allyl. Similar result anyway.

But, my first stop only talks about Allyl. So, to the Claisen Rearrangement. http://library.sciencemadness.org/library/books/organic_reac...

Oh, yah! The analogous rearrangement of Phenol Acetates, is called the "Fries Rearrangement". May require catalyst.

http://library.sciencemadness.org/library/books/organic_reac...

Page 342 onwards.



[Edited on 21-3-2021 by zed]

[Edited on 21-3-2021 by zed]

[Edited on 21-3-2021 by zed]