Sciencemadness Discussion Board

Isolation and Synthesis: Benzyne?

Bromolone - 1-6-2020 at 03:36


Here's another amateur chemist, hailing from India. I was lurking around the forum as a Guest until the recent one-day forum downtime when I decided to register.
Well, I do have some experience handling corrosive acids, bases, and organics, but I shall be synthesising most of the acids as they're not available OTC.

[This question might seem stupid]

Benzyne is a highly useful synthetic intermediate for several reactions and is often produced in-situ due to its instability. The HDDA (hexadehydro Diels-Alder) reaction, dehalogenation of aryl halides, etc are preferred methods for generating arynes but are not 'readily' available to the amateur chemist (as far as I could Google). Most reactions involving arynes call for their synthesis as an intermediate in the reaction. How about isolating it for a short-term?
Diphenylene forms by the dimerization of benzyne, in good yields. Is there a way to 'trap arynes' in an isolable manner - avoiding the dimerization - in a bottle?

I have just ventured into amateur chemistry and do not possess any equipment required for any sort of distillations (coming soon) and haven't performed any yet. My first projects in distillation would be crude ethanol and trichloromethane. I have no hands-on experience in organic syntheses at the moment, but at 18 I find it better to first start off with simple inorganic experiments with safety equipment. :)
I remember how one day my entire class was working in the lab without gloves with nitric acid in school. :o
Also, I do deem ScienceMadness as one of my life-long compaions in my journey ahead.

[Edited on 1-6-2020 by Bromolone]

12thealchemist - 1-6-2020 at 04:05

Welcome to Sciencemadness! And a very interesting question to start with! Unfortunately, the short answer is that it's not possible in the sense you mean. This is because the alkyne is so very strained. There are resonance forms can be drawn:

lossless-page1-640px-Resonance_contributors1.tif.png - 29kB

As you can see, the alkyne and cumulene (which like 180° angles) are bent to 60°, immensely increasing reactivity. Radicals, as you are probably aware, are extremely reactive and rarely stable, and the diradical form also shown helps explain benzyne's extreme reactivity.

The reason why benzyne is never isolated is that it is impossible to do so, except under very carefully controlled conditions. The classic for this is isolation within a matrix. The compound to be studied is prepared in the gas phase, and then frozen in argon or some inert gas at very low temperatures. The low temperature and physical seperation is what enables the compound's isolation.

Another common method (a good example being carbenes) is to coordinate the compound in question to a metal. Somewhat unusual since it uses uranium, but is an illustration. For carbenes, consider Grubb's catalyst.

Finally, encapsulation within a macromolecule is the last option I'm aware of that is commonly used. Again, this is physical separation from other reactive species, enabling "isolation".

As may be clear, most if not all of these options are extremely difficult for the amateur to achieve, and actually lie at the frontier of science. But, having said that, the same used to be said of carbenes - species of the type R2C: with a lone pair. The easiest for the amateur to prepare would be dichlorocarbene, :CCl2. However, these are short-lived species normally, but then persistent carbenes were discovered, of which a large category are N-heterocyclic carbenes (NHCs). Wikipedia gives a good enough background to this area.

Welcome Bromolone

Sulaiman - 1-6-2020 at 05:07

Concentrated nitric acid is best handled carefully without cheap gloves,
fuming nitric acid ignites nitrile and latex gloves.

Bromolone - 1-6-2020 at 07:11


fuming nitric acid ignites nitrile and latex gloves

Thanks, Sulaiman!


most if not all of these options are extremely difficult for the amateur to achieve

Thanks for the references, 12thealchemist! Benzyne is indeed out of our reach to be stored in a bottle :P

(Well, the preprative difficulty of other interesting stuff - say, salts of the pyrylium cation - is far less than benzyne isolation and seems like a good idea for some advanced organic synthesis!)

[Edited on 1-6-2020 by Bromolone]

Cou - 1-6-2020 at 21:19

The smallest possible ring of alternating triple bonds and single bonds is C18.

Bromolone - 3-6-2020 at 07:57

Thanks, Cou.

Cyclooctyne is the smallest cycloalkyne that is isolable and can be stored. Cyclopentyne and some other lower members have been reported as complexes with certain metals.

[Edited on 3-6-2020 by Bromolone]

Texium - 3-6-2020 at 12:02

If you're interested in performing a Diels-Alder reaction using benzyne, it is actually possible in spite of its instability. When anthranilic acid undergoes diazotization and decarboxylation in the presence of a suitable diene, the benzyne that is momentarily formed can be trapped:
It's a really neat reaction!

Anthranilic acid itself is a good intermediate level synthesis once you become more experienced with organic chemistry. Here's my write-up of it: There's links to Chemplayer's excellent video demonstrations from there as well.

Bromolone - 5-6-2020 at 07:36

Thanks, Texium!

I had already planned to follow your preparation of anthranilic acid after nitrobenzene and aniline :D. Happy to see you back on your blog.
And yes, I do need to get more experienced in organic chemistry as I'm yet to prepare phthalimide from the not-so-easily-available-here phthalic anhydride.
The Chemplayer video links on your site only show up the videos as nonexistent on YouTube; all are available here tho: :)

Texium - 5-6-2020 at 07:39

Ah, right. Thanks for reminding me about ChemPlayer. I should change the links to lead to their BitChute uploads instead.

Metacelsus - 6-6-2020 at 04:02

I did my undergrad work on benzyne chemistry (specifically, the HDDA reaction). PM me if you'd like to discuss this more.

How about isolating it for a short-term? Is there a way to 'trap arynes' in an isolable manner - avoiding the dimerization - in a bottle?

Unfortunately no; they're extremely reactive as electrophiles and cycloaddition partners. If they can't find anything else to react with, they'll even rip H2 off of solvent and hydrogenate themselves to a stable arene. Any isolation would have to be in the gas phase, or in a matrix of frozen argon.

Bromolone - 7-6-2020 at 21:26

Thanks, Metacelsus; I had already read your post on your thesis before starting this topic!

Solomons' Organic Chemistry suggests Texium's anthranilic acid method for temporary benzyne trapping, and I have got quite a lot of reagent and apparatus acquisition to do before I start off (shipping delays, basically). I will contact you once I synthesize anthranilic acid so I can later diazotize it and work on some Diels-Alder reactions.

If you might have some other methods in mind (I'm yet to read the doc you uploaded in the thread), I'll discuss them then! :D

[Edited on 8-6-2020 by Bromolone]

Methyl.Magic - 10-6-2020 at 14:00

Benzyne is my field of research. I prepare benzocyclobutene with it by trapping the aryne with an alkene.

The easiest way of generating benzyne is refluxing bromobenzene with NaNH2 (strong base). Personally I prepare them from the fluorobenzene, then deprotonate the alpha acidic proton of the fluorobenzene with BuLi, then on heating LiF is realease along with the aryne :cool:

Bromolone - 15-6-2020 at 01:48

Thanks, Methyl.Magic.

Apologies for not seeing your post soon enough. I'm currently stuck in the transition between high school and uni and I've got several exams coming up; I can't spare much time for the forum nowadays.

Well, strong bases such as NaNH2 are pretty expensive here OTC and it'll take me long before I start off preparing it in the lab. The anthranilic acid route seems to be the most convenient synthesis for now.

The reagents I had ordered have now arrived (lab work to be continued on weekends) and I will return to the forum (in August) with a series of syntheses of organics I've been waiting to do since long (Trimesaldehyde et al).

Methyl.Magic - 15-6-2020 at 03:57

NaNH2 expensive ? really ? This is one of the cheapest strong base...

What is your substrate ? maybe I can help you...

Bromolone - 3-7-2020 at 08:00

@Methyl.Magic: Sodamide is indeed expensive in here - about 14 USD for a few grams. Chemicals that one might find easily in other parts of the world - say acetic anhydride - are banned for individual use by our Narcotics Department and their purchase requires tons of paperwork.
The substrate is the classic for DA reactions: Furan.

And I'm back! (Exams postponed to September :D)

I've been fairly successful in preparing elementary, essential reagents for several experiments and org-chem workups. Benzyne is far from now but I'm now working on mesitylene and other symmetric aromatics. A thread shall follow this up.