Sciencemadness Discussion Board

2,5-Dibromo-1,4-benzoquinone Reactivity?

APO - 13-11-2013 at 20:16

Will 2,5-Dibromo-1,4-benzoquinone react with Sodium Hydroxide or Sodium Methoxide? I can't find any free literature on 2,5-Dibromo-1,4-benzoquinone's reactivity towards bases at all!

PHILOU Zrealone - 14-11-2013 at 05:24

It should behave like 2,3,5,6-tetrabromo-1,4-benzoquinone (bromanil).

The chemistry behind must be the same as for chloranil.
The halogen atoms are very easily exchanged by nitrite, hydroxyl or azido anions; one get from this nitranilic acid (2,5-dihydroxy-3,6-dinitro-benzoquinone), 2,3,5,6-tetrahydroxy-1,4-benzoquinone and 2,3,5,6-tetraazido-1,4-benzoquinone.

If you use the search engine there is a tread of Axt about nitranile and nitranilate salts.

deltaH - 14-11-2013 at 05:54

I have myself reacted chloranal with sodium methoxide in methanol (refluxed). I will try to recall some details for you from memory (it was many years ago):

Although the chloranil didn't dissolve well in the concentrated sodium methoxide/methanol solution I was using, it netherless reacted nicely in time forming a yellow mixture of precipitate and solution under stirring with a bar magnet that also kinda milled the solids on the bottom as it stirred to form a slurry.

After running for some time (can't remember how long) I filtered and washed with an organic solvent (can remember which but probably methanol) to [ultimately] recover a red crystalline flake product highly soluble in organic solvents and a bright white amorphous powder after washing heavily at the filter with water (it was completely insoluble in everything I could try).

IR suggested that the red soluble flakes was indeed tetramethoxyquinone. No surprise, it looked very much like chloranil shiny plates, simply a beautiful deep red colour.

The question was what was the second super bright white amorphous looking insoluble in everything product :) I had made a lot of that too.

IR of this material suggested it was also heavily methoxylated, but it had clear hydroxyl note on the IR, so I concluded I had over methoxylation here attacking the carbonyl as well and upon washing it released the sodium and formed a hemiacetal that proved to be very insoluble and very pretty white and non-crystalline.

This should be reversible then and indeed, heating the white product in a test tube under flame caused vigorous boiling upon melting yielding the same red crystalline product in time as previously obtained (the tetramethoxyquinone). I am thus fairly sure that methanol was eliminated from the hemiacetal (seen as a vigorous boiling) and so this was no problem and I could convert the white product into what I wanted easily.

Long story short, don't be surprised if you possibly obtain a hellishly insoluble white product, in fact, it may be worthwhile to use excess methoxide and target it specifically as it's unavoidable. It is easier to isolate this thing by making use of its extreme insolubility, just wash with copious water, dry and then do the methanolysis by heating and then recrystallise your quinone product.

Hope my suggestions prove useful.

The structures of the two products that I believe were made are:

quinone products.gif - 3kB

[Edited on 14-11-2013 by deltaH]

APO - 14-11-2013 at 10:21

Does 2,5-Dibromo-1,4-benzoquinone react with Diethylamine or Diethyl Ether? I know, this is tedious.

deltaH - 14-11-2013 at 11:29

It would really help if you could give a bit more info APO, what are you after, a base catalyst that won't condense with bromoquinones as well as a solvent system for it?

If so, may I suggest you read up on non-nucleophilic / sterically hindered organic bases. This will also answer your question about diethylamine.

The solvent suitability depends somewhat on the reaction you are attempting as well as the nature of the reagents/products, so again, info please...

[Edited on 14-11-2013 by deltaH]

APO - 14-11-2013 at 12:40

I'm sorry, but I can't find anything on Diethylamine's reactivity towards bromoquiones. I'm guesing Diethyl Ether will just act as a solvent for them? All I know, is that most non-nucleophilic bases decompose 2,5-Dibromo-1,4-benzoquinone on site, such as 1,8-Diazabicyclo[5.4.0]undec-7-ene.

The reason why I want to know is because I came across a reaction that would make a suitable precursor for Cubane 1,3,5-Tricarboxylic Acid, it involved condensing 2,5-Dibromo-1,4-benzoquinone with Bromocyclopentadienone.

The problem is that the Bromocyclopentadienone must be made in situ while in the presense of the 2,5-Dibromo-1,4-benzquinone so that it will condense with the 2,5-Dibromo-1,4-benzoquinone, instead of spontaniously dimerizing.

Bromocyclopentadienone is made by base catalysed dehydrohalogenation of Tribromocyclopentanone, but I'm unaware of any reactants that will do this without reacting with 2,5-Dibromo-1,4-benzoquinone.

So pretty much I need a base catalyst that's inreactive towards bromoquinones, something that will elimanate the two extra bromine atoms on the Tribromocyclopentanone while leaving the ones on the 2,5-Dibromo-1,4-benzoquinone alone, as well as a solvent for all of this to take place.

deltaH - 15-11-2013 at 00:38

Now it makes more sense, thanks for the info.

Okay, a good base catalyst for this from my experience might be DABCO. It usually plays nicely with quinones. I can't gaurantee it specifically with your bromoquinone, but I have personally used it as catalyst for a very neat synthesis that made 2,5-dimethoxy-1,4-benzoquinone from paraformaldehyde in methanol refluxing for several hours with p-benzoquinone and DABCO catalyst (yields and selectivity were okish... but nevertheless).

In regards to solvent, my 2,5-dimethoxy-1,4-benzoquinone was stubbornly insoluble, I don't know if your bromo version will behave in the same way. Anyhow, the only half decent solvent for it that I found was DCM, however, that was not for a reaction where strong bases were present! This is a big problem with things like DCM of course.

So as for a solvent, I hope you don't have the same kind of solubility as I had with the dimethoxy derivative, else you've got a problem.

[Edited on 15-11-2013 by deltaH]

APO - 15-11-2013 at 07:48

Thanks, that seems possible.

But what will eliminate the unwanted bromine atoms on the Tribromocyclopentanone though? Of course while leaving the bromoquinone alone. Will the base catalyst itself work? That's the way Diethylamine functions for the usual dehydrohalogenation.

deltaH - 15-11-2013 at 11:04

DABCO should do a marvelous job of elimination the bromines for you, but then you will need it in stoichiometric amounts and not catalytic.

In that case perhaps you'd do much better with triethylamine, it's so much cheaper, especially if you will be needing stoichiometric amounts of base!

[Edited on 15-11-2013 by deltaH]

APO - 15-11-2013 at 17:58

Wonderful, thanks.

So, just to be clear, DABCO or Triethylamine will work as a base catalyst, remove the unwanted bromines from the Tribromocyclopentanone, all while leaving the bromoquinone alone?

Also, still need a solvent, preferably not Methylene Chloride.

[Edited on 16-11-2013 by APO]

deltaH - 16-11-2013 at 01:50

So, just to be clear, DABCO or Triethylamine will work as a base catalyst, remove the unwanted bromines from the Tribromocyclopentanone, all while leaving the bromoquinone alone?

No, these MIGHT work, you won't know till you try :( The best is to follow a known procedure that has been shown to already work if you want to maximise your chances of success. Failing that, DABCO or TEA are probably half reasonable trial choices but are needed in stoichiometric amounts to affect dehydrohalogenation.

The worry with chloromethanes is the possibility of forming reactive carbenes by the special dehydrohalogenation of an alpha proton... HOWEVER, this is not an easy task at all and requires super bases which DABCO and TEA aren't, so on second thought, DCM might in fact be fine.... again experimentation will tell all!

As you said, I would prefer you don't use DCM, but if you must for solubility reasons, it may well work just fine. So ether is first choice, failing that try DCM.

[Edited on 16-11-2013 by deltaH]

APO - 16-11-2013 at 09:58

Ok, thanks.

Any idea of which may give highest yield?

Regarding DABCO and TEA of course.

[Edited on 16-11-2013 by APO]

deltaH - 16-11-2013 at 14:00

Probably DABCO, but that is speculation! Incidentally, DABCO is one of a few simple amines that has a pleasant odour... smells like peanuts if I remember correctly.

vulture - 17-11-2013 at 01:26

DABCO is very similar in its reactivity to DBU, only weaker, so this might not be a good choice.

APO - 17-11-2013 at 12:45

So what do you think would work vulture?

vulture - 17-11-2013 at 14:41

I'm having a hard time following this synthesis, could you draw a scheme?

By which mechanism do bases like DBU attack the benzoquinone?

APO - 17-11-2013 at 15:54

I could draw the theoretical reaction of which would be wanted, and of how it would be approached if that helps.

I don't know how DBU reacts with 2,5-Dibromo-1,4-benzoquinone, but from what I've read DBU tends to decompose it before can undergo the wanted reaction.

If DeltaH is right that DABCO and TEA typically don't react with bromoquinones, then what would take place is that the DABCO or TEA would react with Tribromocyclopentanone, which would give Bromocyclopentadienone. However, Bromocyclopentadienone quickly dimerizes on it's own, which is not wanted. The wanted reaction is for the Bromocyclopentadienone produced to condense with 2,5-Dibromo-1,4-benzoquinone to give an endo adduct that can undergo photolysis and Favorskii Rearangment to give Cubane 1,3,5-Tricarboxylic Acid. This requires the 2,5-Dibromo-1,4-benzoquinone to be in solution as the Bromocyclopentadienone is made, so that it undergos the wanted reaction, rather than dimerizing.

So ultimantly, reactants that still undergo dehydrohalogenation with Tribromocyclopentanone, but are inreactive towards bromoquinones are needed.

deltaH - 17-11-2013 at 16:36

Amines tend to readily attach to the ring position of quinones under basic conditions, accompanied by the reduction of the quinone to it's hydroquinone form. So for DBU, the fast reaction you have read about is probably the formation of:

DBU addition.gif - 2kB

While for some reason the DABCO version is not favoured, probably because of steric hindrance. The DABCO equivalent that would have formed would be:

DABCO addition.gif - 2kB

In this animation of the 3d structure, the extreme steric hindrance is clear (click on structure to see animation):

DABCO addition animation.gif - 382kB

[Edited on 18-11-2013 by deltaH]

APO - 17-11-2013 at 18:05

Thank you DeltaH, that's very helpful.

Below is a rough draft of the proposed reaction scheme:

The question mark specifies where the suitable reagents from this threads' conclusions will come into play.

vulture - 18-11-2013 at 00:07

1) Do we have any references for this attack of amines on quinones? If yes, please supply. The proposed reaction involves a proton transfer which I would suspect to be hard under aprotic conditions.

2) I don't see how DABCO would cause more steric hindrance than DBU.

3) You obviously got this reaction from the literature, again, a reference would be nice, plus, which conditions do they use?

deltaH - 18-11-2013 at 01:07

Quote: Originally posted by vulture  
1) Do we have any references for this attack of amines on quinones? If yes, please supply. The proposed reaction involves a proton transfer which I would suspect to be hard under aprotic conditions.

2) I don't see how DABCO would cause more steric hindrance than DBU.

3) You obviously got this reaction from the literature, again, a reference would be nice, plus, which conditions do they use?

(1) I worked with quinone addition reaction some several years ago, references are on an old laptop that I have to dig out. It's very old chemistry (~100 years if I recall from an organic chemistry textbook). I tried a quick google search now, but couldn't find anything, so I will describe what I can and maybe the op can do better if he is so inclined.

My apologies, but I am very busy this week so can only dedicate more time to this next week. I'll describe the reaction and perhaps either the op or someone else can chase this up:

The reaction that got me into quinone chemistry was in fact a condensation between aniline and benzoquinone with a base catalyst (this is the 'very old chemistry' bit). Aniline adds on the 2 position via nitrogen, forming a hydroquinone derivative that then get's reoxidised in situ by unsubstituted quinone (which is a stronger oxidant) and then the addition happens again on the 5 position, followed by another reoxidation. In the end, you end up with a 2,5 aniline derivatized quinone and require at least 1.5 equivalents of quinone to aniline and form 1 equivalent underivatized hydroquinone as a co-product.

I have also done this with melamine as the amine and formed pitch black polymers from this type of reaction. I have filed a patent for that incidentally, turns out they were excellent support materials for metal carbonyl cluster based catalysts.

Toma, N.V., University of Cape Town (2012), Stabilised and activated metal cluster complex based catalysts and their preparation, Int Pat Appl No PCT/IB2012/056681.

In fact it's not just amines, quinone chemistry in general tend to form 2,5 addition products in many variations, even the chloranil synthesis from conc. HCl and H2O2 (patent) proceeds via an isolatable 2,5-dichloroquinone.

As I've said before, I've also prepared a 2,5-dimethoxy-benzoquinone by DABCO catalysed addition in methanol and paraformaldehyde. I did have success with a google search for you on that:

Colletti, R. F., Stewart, M. J., Taylor, A. E., MacNeill, N. J. and Mathias, L. J. (1991), 2,5,-Dimethoxy- and 2,5-di-n-butoxy-1,4-benzoquinone reactions and polymerization with 1,6-hexanediamine. J. Polym. Sci. A Polym. Chem., 29: 1633–1638. doi: 10.1002/pola.1991.080291113

I know you are hungry for more, but I am afraid that is the best I can do for now.

(2)So in the case of DBU, since I know that ring additions on the 2 and 5 positions occurs readily with quinones under basic conditions, assuming DBU reacts readily with quinone as the op suggested, this was merely my suggestion of what might be happening. DBU is bulky, but it can twist 90deg. to the quinone and so 'slot' in between the bromine and -OH (not easy, but hypothetically possible). Recall the double bond on DBU is resonant between the two nitrogens making rotation possible.

DABCO, on the other hand, is a bulky 3d 'cage', it cannot twist into any kind of better fit as my animation shows, which is why I would guess it may be a better choice than DBU.

Finally, in regards to your point about protic versus non-protic solvents, you may be right, however, I would not dismiss this so quickly in aprotic solvents. In the end of the day, it either happens or it doesn't, for whatever reasons.

[Edited on 18-11-2013 by deltaH]

APO - 18-11-2013 at 17:17

Thanks for the additional info DeltaH.

Vulture, the literature that suggests the target reaction, and mentions the reactivity of DBU with bromoquinones is here, however, all of there approaches to make the endo adduct failed. They tried a somewhat similar approach, but with much too reactive reagents.

So, vulture, if aprotic solvents aren't very favorable, what do you suggest?

Also, If you don't think DABCO or TEA will work, do you have an idea of what will?

vulture - 19-11-2013 at 14:37

I had a quick look at the file, but not long enough to say anything definitive.

It seems that they completely abandoned the route you are proposing, correct?

What do you mean with "much too reactive reagents"?

APO - 19-11-2013 at 14:57

I wouldn't say they abandonded it, as I don't know if they even thought of it. But yeah, what I'm proposing is considerably different.

What I mean by "much too reactive" is that they tried highly reactive bases, like Potassium Tertiary Butoxide, and pretty much methods that I doubt whould have a chance of working in the first place.

However, the reaction that shows how to get to the endo adduct, and ultimantly Cubane 1,3,5-Tricarboxylic Acid, was originally thought of by Eaton, so I think what's presented is still valid.

deltaH - 22-11-2013 at 04:28


Back from my trip and managed to get my old laptop working (it's power supply was another story). Anyhow, the info is from Organic Chemistry by Finar, I.L (1959), 3rd ed., pp.639-645

I couldn't find this book online, but I found a later edition and browsing through in about the same area, found the same info, you can read this online at:

That page specifically discusses this ring addition chemistry of aniline to benzoquinone and from a few pages before gives a nice introductory discussion about quinone chem in general, you may find it useful in your quinone chemistry.

Hope that helps you!

[Edited on 22-11-2013 by deltaH]

APO - 22-11-2013 at 11:20

That has nothing on reactivity of non-nucleophilic bases with bromoquinones, so I don't really think that's relevant, but thanks, anyways.

Again Vulture, If you don't think aprotic solvents, DABCO, or TEA are suitable for any of this, do you have any ideas?

deltaH - 22-11-2013 at 11:42

No it does not have anything on the reactivity of non-nucleophilic bases per say, just simply supplying the reference as requested, that certain amines are known to add to the 2 and 5 positions of quinones coupled with a reduction of the quinone and then reoxidation by unsubstituted quinones. It's not so easy to find... I had no luck when googling it, for example. I promised before that I would give it a better go after my hectic week was over and so now I could :) I had to pull it from an old presentation of mine and then find some online source for it.

[Edited on 22-11-2013 by deltaH]

APO - 22-11-2013 at 20:33

Oh, I see.

Also I feel it is important to note that specifically in this case, from what I've read, ketal derivatives do not work, and neither do 2,2,5 bromine groupings.

From what I know, the only possible brominated derivative of Cyclopentanone that will work for this reaction is the ketone form with 2,3,4 bromine groupings, so using 2,2,5-Tribromocyclopentanone or it's Ethylene Ketal isn't possible.

So, even though there are other derivatives that seem like they would work, it apears that only one will do the job.

Additionally, on the reaction scheme I posted the last step is actually two, hv, and then NaOH, not at the same time.

Below is the revised, more comprehensive version, including steps for 2-Cyclopenten-1-one, as I will have to make it.

So, any suggestions on what will work for the DABCO step if this doesn't seem likely to work?

DeltaH thinks it has good probability, but Vulture, not so much.

[Edited on 23-11-2013 by APO]

deltaH - 23-11-2013 at 00:32

Are you following published steps up to the cyclopentenone or proposing? Do you know the conditional details and yields?

[Edited on 23-11-2013 by deltaH]

vulture - 23-11-2013 at 03:33

In the second step, are you sure you will only selectively epoxidize one double bond?

I don't understand where the other isomer of the dialcohol comes from.

How do you convert the dialcohol to the ketone with p-TsOH?

I have no idea if DABCO will work or not.

APO - 23-11-2013 at 11:06

DeltaH, all steps up to 2,3,4-Tribromocyclopentanone have been successfully done before, as you know, the part with 2,5-Dibromo-1,4-benzoquinone, DABCO, and Diethyl Ether is the sketchy part. The total yield up to the mixture of Cyclopentendiols is 70%, and the yield of conversion to 2-Cyclopenten-1-one is 60%, so the total yield up 2-Cyclopenten-1-one is 42%. Step one is carried out at 270C, step two at 15C, step three at 5C, and step four at 60C while under vacuum. However, I don't feel the need to go into detail right now.

Vulture, the yield of 1,2-Epoxycyclopentene is nearly quantintative, so I think that it's favored for some reason. I'm not sure why the hydrolysis of the 1,2-Epoxycyclopentene gives two isomers though. I believe the conversion of the Cyclopentendiols to 2-Cyclopenten-1-one is an acid catalysed cycloaddition of some sort.

[Edited on 23-11-2013 by APO]

deltaH - 23-11-2013 at 12:05

...and that Vulture... is why you ask "Are you following published steps up to the cyclopentenone or proposing? Do you know the conditional details and yields?" first :P

Thanks APO, the reason I asked is because the same concerns occured to me as did to Vulture, except the 1,3 product made sense to me, but I was also worried about the selectivity of the partial oxidation and acid catalysed dehydration.

APO - 23-11-2013 at 12:37

You're welcome.

Speaking of conditional details, do you have an idea of what temperature the DABCO step would preferably be conducted at?

Also any idea of work up/purification?

deltaH - 23-11-2013 at 14:10

Answered by U2U.

APO - 23-11-2013 at 16:15