Author Topic: hey! Bandil, there is for sure great interest...  (Read 3277 times)

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Xicori

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hey! Bandil, there is for sure great interest...
« on: June 21, 2004, 03:16:00 PM »
hey!

Bandil, there is for sure great interest on your research, keep on posting!

And I´m sure there will be a lot bees have to add when they try the procedure for themselves...

...SWIM is very limited on time right now, but your method is on top of my list of what to try out next ;) A different substrate like 2,5-Dimethoxy benzyl chloride/bromide might be also very interesting (i´ll try this out for sure, just wait til august)!

keep the wonderful work up, many people are very thankful for it (even if they don´t post here!)

...and the Novel discourse is a way better home for your threads than the stimulants  ;D

have a nice summer!

armageddon

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Wow! Nice done!
« Reply #1 on: July 08, 2004, 08:42:00 AM »
My compliments to you Bandil - very impressive! A real breakthrough would I say.  8)

Thanks for your work, keep on.

Greetz A


armageddon

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much cleaner acetylacetonate salt..
« Reply #2 on: August 02, 2004, 08:41:00 PM »
To get very clean sodium acetylacetonate suitable for above Grignard rxn, you should try the following: suspend 20g NaOH(s) in 250ml ice-cold abs. EtOH in RBF, stir to dissolve as much as possible, place in cold water bath and let cool. When done, attach reflux condenser and slowly add ~1.05 eq. acetylacetone (~53ml) via addition funnel while stirring very vigorously. When all acetylacetone is added, the reflux condenser is replaced with a three-way adapter fitted with downward condenser and the (viscous) suspension of crystals/ethanol/water is reduced to at least 2/3 of its volume using slight vacuum, then everything is cooled very slowly, first in cooling bath, then in fridge. The precipitated acetylacetone*Na is vacuum filtered and rinsed with cold, anhydr. acetone and the remaining mother liquor is again concentrated to obtain a second crop of crystals after again adding some dry acetone to it.

The resulting crystals are put into a dry RBF which is evacuated to dry them, as usual. The yield is only 85% of theory (around 60g from 0.5mol acetylacetone), but purity is outstanding (shiny little plates) - and concerning the few grams of acetonate salt remaining in the residual mother liquor: well there are always losses, right? The price to pay for purity...

(although I don't know if high purity is really essential in this case...  ;) )

If you experience problems with Grignards not wanting to start when using acetylacetonate prepared like described above, simply dry your acetylacetone*Na in a desiccator over molar sieves for some days next time - should become "bone-dry", too. And if it still doesn't work, you know at least the reason was not the Na salt being too wet... :)

Greetz A


armageddon

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anhydrous.. (?)
« Reply #3 on: August 10, 2004, 12:09:00 AM »
Hi!

A friend of mine (I'll call him SWIA for simplicity  :) ) just did his first Grignard reaction with benzyl chloride and acetylacetone (sodium salt), and succeeded...

OK so far nothing important, but the surprising detail: He didn't dry any glassware prior to using it, nor did he use drying tubes, and the weather was only so-so (high humidity and temp.) - he simply dried the BzCl/ether solution with molecular sieves, as well as the ether he used as solvent, and SWIA used in-situ drying (he just added several grams mol. sieves to the Mg/Et2O prior to adding the BzCl-soln., like described by Bandil).

And his molecular sieves were 4 Angstrom pore size (4A) and were not dried/activated by microwave or other methods, just used directly out of the (air-tight) container..

And all glassware SWIA used was as moist as the air was that day - and the grignard complex formed after stirring the Mg/Et2O together with 1/4 of the BzCl/Et2O soln. and warming the flask with bare hands, just like described...

...but SWIA told me he would strongly advise using a big reflux condenser or even better double-surface condenser instead of a vigreaux - he lost 250ml ether during the rxn, and had to leave the lab for a while due to becoming a bit drowsy... ;D  (so better use that reflux condenser with cold water)

But the point is: even a bee with sloppy technique (like SWIA) and absolutely NO experience with grignards is able to reproduce the results of above method, if the necessary precautions are taken (ether is explosive, volatile, etc.etc.blabla).

Don't be afraid, try it! With proper in-situ drying, this grignard rxn is really hard to screw up IMO!

(Oh, and don't make the same mistake like SWIA and store your recovered ether in the same PE flask whose bottom is still covered with the mol. sieves from the initial solvent drying: his ether got dark-brown overnight upon standing in the fridge and scared the shit out of SWIA because of all the stories bout self-ignition of dried, peroxide-containing Et2O during shaking - until he figured to add some water/FeSO4 and let again stand overnight instead of shaking it - which luckily restored both the colorless appearance of the Et2O and SWIAs feeling of relative safety..  :-[ )

Greetz A


armageddon

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strange distillate...
« Reply #4 on: August 10, 2004, 11:27:00 PM »
Hi bees!

My buddy SWIA vac distilled his ketone gotten from said AcAc Grignard twice - and collected some strange fractions..(?)

First, some different clear liquids came over, followed by a nice fraction of yellow oil - so far so good. He then decided to redistill, because the smell of the oil was still somewhat disgusting and not really like phenylacetone at all...

Said done. First some small amount of clear liquid came over below 80°C at 270torr. Then, a small fraction was collected at 150°C (corresponding to ~185°C at 760torr) - probably benzylchloride, SWIA thought - at least it would explain the disgusting smell of the raw product..
Then, nice greenish ketone came over at above ~165°C (just like P2P should), but the amount was only roughly half of the original volume!
Then distillation ceased and SWIA had to crank the heat control up to over 350°C to be able to collect a large fraction between 210° and 230°C - WTF is that???

Appearance of the unknown substance is oily, slightly yellow and the bp should be around 260°C at ambient pressure - maybe 4-benzyl-3-pentene-2-one? Its bp would match, and

https://www.thevespiary.org/rhodium/Rhodium/pdf/p2p.acac-grignard.pdf

  states that said ketone is obtained by heating the bis addition product of this reaction at 130°C under vacuum followed by distillation, so maybe...?

This really puzzles me, especially because you guys have spent that much effort in analyzing the product!? (did SWIA use too little HCl for hydrolysis maybe?)

Any ideas about what could've happened?

[EDIT] after some more 24hours in the fridge, the P2P SWIA isolated has still its beautiful colour - while the higher-boiling fraction has become strongly yellow-tinted[/EDIT]

THX A


armageddon

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another reply to myself...
« Reply #5 on: August 18, 2004, 12:16:00 PM »
The strange high-boiling ketone SWIA isolated during redistilling his phenylacetone didn't only take on a deep yellow/orange color, but also solidified after being kept in the fridge (+7°C) for one week...

Appearance is yellow/white, the crystalline mass consists mainly of many clear needles...

WTF is that?

Input is greatly appreciated!

Greetz A


Bandil

  • Guest
The dehydration product!
« Reply #6 on: August 18, 2004, 01:25:00 PM »
Perhaps the dehydration product? It's higher boiling and will most likely solidify upon storage at low temperatures...


armageddon

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lazy..
« Reply #7 on: August 19, 2004, 03:40:00 PM »
Beat me for not wading through the original reference, but:

How does the dehydration product form? Or better said: what did SWIA do wrong? He told me that the "good" ketone he isolated was successfully aminated via leuckart with good yield.. so some minor error must have happened, I'd suppose? I didn't notice you got any of this wierd by-product - did I miss something?  :)

Greetz A


Nicodem

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Maybe acid remains?
« Reply #8 on: August 20, 2004, 12:50:00 AM »
Just avoid using any acid stronger than Bandil used to quench his Grignard product (he used ammonium chloride, I think) and most importantly wash the ether with a bicarbonate solution before doing the disstilation. As long as there is absolutely no traces of acid present while distilling, the elimination side reaction should bee kept at minimum (in my opinion at least).
Anyway, you did not gave details on your work up of the Grignard. It might have been something else?


Bandil

  • Guest
I used dilute HCl in the last run, which gave...
« Reply #9 on: August 20, 2004, 09:14:00 AM »
I used dilute HCl in the last run, which gave about 20% dehydration product. I also forgot to wash with bicarbonate... Great idea  :)

I'll be sure to try that out in the forthcomin up-scale run  ;)

Regards
Bandil


armageddon

  • Guest
well then
« Reply #10 on: August 20, 2004, 02:33:00 PM »
Hm, I used excess HCl 'cuz I wasn't sure about its concentration - too bad...

Bandil: be sure to use good cooling and a condenser with wide inlet, and clamp everything very tight - I don't know if you read my post in "lab mistakes", but the pressure buildup can become a serious problem with scaleups... ::)

(thanks for your responses btw!)


[edit]

Oh, the workup - of course: after hydrolysis, the ethereal layer was separated and the rxn extracted 2x with more ether, then the combined extracts were washed with brine, dried over Na2SO4 and solvent removed with a rotovap  8)  - the resulting oil was vacuum distilled, discarding a large forerun of clear liquid, then yellow oil was collected. This was redistilled (vacuum/vigreux) and gave less than 30% yield of very clean P2P, the remainder distilled at >200° with same vacuum and was dark yellow and solidified after one week at 7°C.

I guess it was the acid, too much maybe...

Greetz A


armageddon

  • Guest
strange
« Reply #11 on: August 21, 2004, 06:22:00 PM »
Another try was made, using 0.54 mol BzMgCl and, unfortunately, 30 grams sodium acetylacetonate and 24ml acetylacetone in ether (due to a brain glitch; the actonate salt was prepared in large quantity time ago, and the chemist thought he still had enough, until during the reaction, when he realized there was in fact only 30g left  :( ).

Maybe this accounts for the low yields, too - the bis addition product may have formed in significant quantity, but anyway: yield from this 0.54 mol run was only 13.4ml phenylacetone! (too disappointed to calculate any yield anymore  >:( ) And the hydrolysis as well as the vacuum distillation of crude product was done *very* carefully. And all traces of acid were removed by shaking the ethereal extracts of rxn twice with sat. sodium bicarbonate solution, followed by 2 washes with brine. Ether was stripped using a rotavap, the remainder was distilled under 20torr vacuum and P2P was collected between 108° and 118°C (note that steam temp. fell from >50°C to 24.5°C before it suddenly jumped to >100°C after a long while of heating - all fractions collected before were clear liquids with bp's below 70°C, therefore the ketone should've been distilled very sharply, with good separation from by-products).

The remainder was flooded with 230ml H2O and steam distilled, hoping to reverse said dehydration process somehow, and is still in progress...

Honestly, I don't think the dehydration due to traces of acid being present is the explanation for this wierd, high-boiling side product (which is sadly more the main product  :( ). Maybe something was wrong with this huge batch of acetylacetone*Na. The Mg and ether shouldn't be the problem, they're both expensive quality grade reagents, the AA is tech grade (still very xpensive though  :) ), and  - lo and behold - the BzCl used is analytical grade, well branded too  8) , so the reactands are not the problem I think. The technique should be good enough to reproduce Bandil's results (at least getting the Grignard to start isn't any problem, and separating, washing and distilling organic liquids belongs to the few things SWIA as well as me are pretty familiar/skilled with).

HELP!

Are there any important things to consider (besides dryness of reaction, patience, attention, safety, precise measurement and practice of course  :) ) when doing this reaction?

Is the purity of the acetylacetonate salt essential for success maybe? I suspect that the salt that was used in the several miserable trials maybe contained traces of NaOH and therefore fucked up everything with "in-situ hydrolysis" while adding it? (just my thoughts; I'm a bit lost...  :( )

Greetz A


Bandil

  • Guest
Acetylacetonate purity
« Reply #12 on: August 22, 2004, 09:41:00 AM »
Hi Armageddon!

Sorry to hear about those poor yields  ::)

First of all, the purity of the acetylacetonate is not one of the limiting factors. The highest yield I got was with brownish - ugly looking sodium acetylacetonate (overbaked in the oven - heh). It's obviously important that it's dry, but it seems that you got that covered.

I think the problem is located in your acid hydrolysis / splitting technique. Heres what bothers me in your description: And the hydrolysis as well as the vacuum distillation of crude product was done *very* carefully.

In the original article, they state that: This dehydration is a delicate operation; in some runs, only the splitting product, phenylacetone (IX) could be isolated

I think that using dilute hydrochloric acid for the acid splitting operation will increase your yields. The reasoning behind this is that the hydrochloric/water layer will be less overall polar than a saturated ammoniumchloride/water layer. In theory this would allow more of the ether/product layer to mix with it, and thus increasing the water contents during the acid hydrolysis. This could push the equilibrium in the right direction.

But more importantly: After stripping the ether and prior to distilling the ketone I heated the whole shebang to about 150°C at atmospheric pressure for about an hour, to facilitate the "deacetone'ation"(step IVb to IX).

So next time, try treating it like you would with a real woman - rough  8)

Give it a whirl with this scheme:
1: React the grignard reactant with the sodium acetylacetonate.
2: Reflux for 4 hours.
3: Add dilute hydrochloric acid and stirr
4: Separate the organics and extract once more with ether
5: Wash the ether with aq. bicarbonate, twice with water, once with brine and finally dry it with whatever you have at hand.
6: Strip the ether
7: Heat the remaining organics to 120-150°C at atmospherical pressure for about one hour.
8: Distill the P2P under vacuum

Regards
Bandil


Lilienthal

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Re: The Mg and ether shouldn't be the problem,
« Reply #13 on: August 23, 2004, 02:02:00 AM »

The Mg and ether shouldn't be the problem, they're both expensive quality grade reagents,...



Have you explicitly ultra-dried your ether? 'Quality grade' from the bottle might not be enough.  :)


armageddon

  • Guest
Thanks guys
« Reply #14 on: August 23, 2004, 02:41:00 AM »
Lilienthal: lemme cite from Bandil's last post here  :) : "It's obviously important that it's dry, but it seems that you got that covered."

(in fact I sometimes have problems with recycled ether becoming brown, i.e. developing peroxides, within 1 hour; although keeping it cooled and in the dark! I think its due to drying it too thoroughly...  :)  - and initiating the grignard reaction luckily is no problem for me)

So I would say drying is not the issue. (remaining H2O is 0.001% with 4A mol.sieves, and I hope you don't think I'm not capable of adding enough drying agent and/or be patient enough, or that I don't use air-tight containers for drying!?  :P )


Bandil: SWIA used dil. HCl for hydrolysis, but didn't heat (reflux?) the crude products after solvent removal. And I think this caused SWIAs dreaded results. Also after reacting the grignard complex with the AA salt, reflux was done for 9 hours (chemist was tired from supervising the reaction for hours and left lab to take a short nap, damn ether  :) ).

As said, no heating before vacuum distilling was applied. But I would think that during distillation, the acetone should spit off, too? Temperature of the liquid is well above 130°C if steam temp. is >110°C, and the vacuum should even facilitate the "de-acetonylation" (my all-around favorite "LeChatelier" again). But of course the extra 1h heating will bee included in future trials.

Any more input before SWIA proceeds with his next try to reproduce the >60% yield result?

If not: thanks anyway, your help at least gave me motivation  ;)

Greetz, A


Organikum

  • Guest
Add some copperwire to your dry ether and...
« Reply #15 on: August 23, 2004, 09:43:00 AM »
Add some copperwire to your dry ether and suppress peroxide formation this way.

ATT.: This doesnt destroy peroxides which are already formed.


moo

  • Guest
It would be nice if peroxides could be ...
« Reply #16 on: August 23, 2004, 01:16:00 PM »
It would be nice if peroxides could be detected by a brown colour, but I strongly doubt it. That would've made the KI-starch test papers and other tests for peroxides obsolete decades ago. It most likely is other impurities. So wash your ether properly before distilling it.

I also disagree about the need for a condenser with a wide inlet. The trick is to get the reaction to start before most of the halide has been added. Then you can add more and maintain a gentle reflux all the way, without fear of sudden exotherms. A textbook gave the general directions for performing a Grignard on small scale, the instructions told to add at most 1/10 of the halide in the beginning. The crystal of iodine does wonders too.


armageddon

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my problem is not ether but low yield! *lol*
« Reply #17 on: August 23, 2004, 02:35:00 PM »
Impurities boiling at 34.5°C? And becoming brownish only when the ether is dried thoroughly? Being easily removed by washing with water/FeSO4? I doubt that. Especially as 2 bicarb washes followed by 1 water wash and 2 brine washes were done on crude product before solvent removal - thoroughly enuff?  :)

Think copper wire will do fine to prevent this from happening though. (thx)

And Moo, I would not have stated it if I didn't knew about the danger of condensers not being able to handle huge amount of ether while still allowing for condensed ether to fall back, therefore leading to significant pressure buildup - and this is not a question of how much halide solution to add in the beginning; above a certain amount of solvent used, the reaction simply produces a lot of heat and vapor NO MATTER how careful the addition is done - maybe the wide inlet condenser isn't really necessary, but then a good cooling bath (ice/salt) is! I fail to understand the purpose behind advertising low security methods?!

Greetz A


moo

  • Guest
Don't get me wrong, I don't mean to be an...
« Reply #18 on: August 23, 2004, 05:33:00 PM »
Don't get me wrong, I don't mean to be an asshole. I've seen enough heated discussion here in the Hive lately  :( , so  I'll give you my reasons for my opinions.

My problem is with theories that seem unreasonable and unjustified. The FeSO4 procedure is a time-tested method for removal of peroxides. The presence of peroxides can be verified easily and I've seen it work (the KI-starch test paper was used for verification). I've also read my share of literature regarding reactions of peroxides and metal ions.

My rationale is based on the fact that the peroxides from ethers are colourless. The colour has to originate somewhere else, even if the peroxides took part in the reactions. Surely the boiling point of the mixture is the boiling point of ether, but that doesn't mean small amounts of low-boiling impurities, for example acetone (bp 56.5°), won't come over with the ether. Acetone is a bitch to remove completely with water washes. Various salts dissolved in the water make it even less soluble in it. Acetone can also undergo an aldol condensation with another molecule of acetone, a process where water is eliminated and absorbing water is what molecular sieves are good for. When the condensation products condensate with more acetone you have polymerization that can lead to compounds with long conjugated chains. Such properties often make organic molecules coloured. Does that sound reasonable? Washing with bisulfite can be used to remove compounds bearing a carbonyl group, the same ones that can undergo an aldol condensation, were they acetone or something else. Maybe a few of those washes could give better results?

Regarding the Grignard. I've never done a Grignard with BnCl, so I don't know how bad it is, although I've done a few Grignards with other compounds. What I said was what mostly a reaction to your post in the lab mistakes thread, but I surely didn't suggest being careless. That would be promoting insecure methods. What you said of an ice bath on hand is what I was after and I should've said so. I also promise you that I'll remember your advise if I ever do a Grignard with BnCl. ;)

However, it is very good to see people trying out new procedures and discussing them! :)


armageddon

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my problem isn't...
« Reply #19 on: August 24, 2004, 05:30:00 AM »
Well, the stupidity of my "stupid lab mistake" was using an improvised condenser connected to the rxn flask with glass tubing which was unfortunately not capable of allowing for reflux, due to the ether vapors pushing everything into the condenser instead of letting it fall back into flask. So in fact I used a condenser with narrow inlet and plop! - crash! - (cough, cry, gasp for breath and start swearing like a drunk, 80 year old sailor while wiping up the mess  :) ) - and I can just tell that this doesn't happen if a normal condenser is used!

And about my ether: it is OK! I can re-use it without problems, as long as I shake every discolored ether with FeSO4 soln. and then dry it again. And I don't know: every chemistry textbook tells that ether becoming brownish is due to peroxide development, and my ether if it has become brown responds pretty good to the usual techniques of peroxide removal...

Left to say: stockpile ice cubes, dry your ether and be careful with adding the BzCl *slowly*. Good luck.

Anyone got any ideas about hydrolysis of the "acetyl-P2P", before SWIA tries it a last time (tired of unseccessful grignards  :( )?

Greetz A