The Vespiary

The Hive => Novel Discourse => Topic started by: Rhodium on January 12, 2004, 09:11:00 PM

Title: P2P by grignard addition to acetylacetone
Post by: Rhodium on January 12, 2004, 09:11:00 PM

Someone really should take a closer look at this reaction, which is the addition of benzylmagnesium chloride to acetylacetone. The authors seems to have a real tough problem on their hands - their desired addition product is violently unstable, and decomposes to phenylacetone upon the slightest treatment with acid. They aren't explicitly mentioning any yields, but 96 mL benzyl chloride, 19g Mg and 40 mL acetylacetone gives 140 mL of "mainly" IV, which upon heating decomposes to "mainly" phenylacetone (IX). Shouldn't be too bad, all in all - and why shouldn't the reaction be extendable to substituted P2P's?

Mono- and bis-Addition Products of Benzylmagnesium Chloride to Acetylacetone
A. Barabás and A. T. Balaban

Tetrahedron 27, 5495-5503 (1971) (https://www.thevespiary.org/rhodium/Rhodium/pdf/p2p.acac-grignard.pdf)

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

Abstract
The addition of excess benzylmagnesium chloride to acetylacetone affords a mixture of mono- and bis-addition products, whose relative yields suggest that the mono-addition isa reaction of the enol tautomer and the bis-addition a reaction of the diketo-tautomer. 4-Benzyl-4-hydroxypentan-2-one (IV), the primary mono-addition product, is easily dehydrated to 5-phenyl-4-methyl-3-pentene-2-one (XI), which was isolated and characterized. This dehydration is a delicate operation; in some runs, only the splitting product, phenylacetone (IX) could be isolated.


Experimental

Addition of acetylacetone to Benzylmagnesium chloride

Benzylmagnesium chloride was prepared as usual from 19.2 g Mg turnings and 96 ml (0.8 moles) PhCH₂Cl in ether. To this solution 40 ml 10.4 moles) of acetylacetone in 50 ml ether were introduced dropwise under vigorous stirring ata rate which allows the mixture to reflux gently. The stirring under reflux was maintained for an additional 6 hr period by heating. The mixture was then cooled by an ice-salt bath and 200 ml of ice-cold. sat. NH₄Cl(aq) added under vigorous stirring continued till nearly all solid material dissolved. The cold solution was filtered and the precipitate washed several times with fresh NH₄Cl(aq). The ethereal layer of the filtrate was separated and the aqueous phase extracted with ether. Combined organic layers were dried (Na₂SO₄) and the ether evaporated at room temperature. About 150 ml of yellowish oil was obtained. consisting mainly of 4-benzyl-4-hydroxypentan-2-one (IV), which could not be purified because it underwent dehydration.

Splitting of benzyl-methyl-acetonyl carbinol (IV) to benzyl methyl ketone (phenylacetone, IX)

By heating product IV without I₂ (or in a few irreproducible runs even with I₂), 40 ml of a different distillate, b.p. 100-130°C/10mmHg was obtained. Its main component IX could be obtained by refractionation at 80°C/6mmHg or 71°C/3mmHg and yielded on treating with DNPH only a yellow adduct, which after several recrystallizations from dioxane melted at 156°C. Literature mp for X, 152-4°C.

Title: Someone really should take a closer look at...
Post by: Nicodem on January 15, 2004, 10:25:00 AM

Someone really should take a closer look at this reaction

The key part is the retro-aldol reaction and you are right, it should be extendable to more interesting P2P’s. One trouble is the need of two equivalents of the Grignard. When you use precious benzylchlorides this is unacceptable. But maybe that can be solved by using an alkaly salt of acetoacetone in the first place instead of plain actoacetone.

Otherwise it is very promising indeed.
Now, who among us is the most fanatic Grignard fan? :P

Title: High! Thats really a procedure that should be...
Post by: Xicori on January 15, 2004, 05:11:00 PM

High!

Thats really a procedure that should be tried out  8)

As Swim´s somewhat a grignard fanatic i´ll try out as soon as i can get my hands on acetylacetone...

So much to do, so little time   ::)

best wishes,
xicori

Title: Great Xicori!
Post by: Nicodem on January 15, 2004, 07:25:00 PM

Great Xicori!

But I hope you are aware that when you go trough the trouble of preparing the Grignard from a benzylchloride all you have to do to get a P2P is to add acetonitrile (PhCH2-MgCl + MeCN -> Ph-CH2-CO-Me) without even using two equivalents of the Grignard. But I would very much like to see the difference in the yields if using, for example, a well dried magnesium salt of acetoacetone.

P.S.: I never ever heard anybody being enthusiastic about the Grignard reaction before. I actually admire you. I would very much like to have the equipment good enough to perform a Grignard.

Title: Hey Nicodem! Yeah, i know the grignard-rnx...
Post by: Xicori on January 15, 2004, 07:48:00 PM

Hey Nicodem!

Yeah, i know the grignard-rnx with acetonitrile, but it is very low yealding and also "old stuff".. trying something new is always more exciting [cool}

performing a grignard-rnx isnt as hard as most people think! All you need is a effecticve condensor, a 2N-Flask, 2 drying tubes and some molecular sieves to drie your solvent :)

usually grignards  are a lot of fun, because there is really much going on in the flask to look at :) - the disappearing of the idodine colour..Mg starts to float around, and seconds later the solvent is at reflux temperature ;)

so best wishes,
xicori

Title: Alternative Acetylacetone Syntheses
Post by: lugh on January 16, 2004, 02:49:00 AM

An alternative synthesis of acetylacetone, using sodium amide as the base, From JACS 66 1220-2 (1944):

(https://www.thevespiary.org/rhodium/Rhodium/hive/hiveboard/picproxie_imgs/djvu.gif)

These patents may also bee of interest:

Patent US2158071 (http://l2.espacenet.com/dips/viewer?PN=US2158071&CY=gb&LG=en&DB=EPD)

Patent US2369250 (http://l2.espacenet.com/dips/viewer?PN=US2369250&CY=gb&LG=en&DB=EPD)

Patent US2395800 (http://l2.espacenet.com/dips/viewer?PN=US2395800&CY=gb&LG=en&DB=EPD)

Patent US2398685 (http://l2.espacenet.com/dips/viewer?PN=US2398685&CY=gb&LG=en&DB=EPD)

;)

Title: Grignard fiends
Post by: SilverSurfer on January 16, 2004, 03:13:00 PM

and by the way: is there something like a grignard tip to rule them all, in terms of starting a (aryl)grignard and keep it runnin without blasting with the heatgun all the time. Ultra sonic (+Iod) or dimethylaniline maybe?

Title: Grignard Reaction Initiation
Post by: Rhodium on January 16, 2004, 04:38:00 PM

Post 383426 (missing)

(Rhodium: "Grignard Reaction Initiation FAQ", Chemistry Discourse)

Title: my problem with grignards...
Post by: hypo on January 16, 2004, 04:50:00 PM

is not that they don't start, usually they do.
but that many of them turn to "stone" making magnetic
stirring more or less useless  :P .

Title: THF instead of ether
Post by: Bandil on March 22, 2004, 10:23:00 AM

Hi!

I have a premade 2M THF solution of benzylmagnesiumchloride. Any neat suggestions on how to use this instead of an etheral solution? It's of course the work up im concerned about, as THF and water is miscible.

Perhaps stripping most of the THF under slightly reduced pressure and extracting the aquous mixture with DCM?

Regards
Bandil

Title: easy to make THF and water separate
Post by: Rhodium on March 22, 2004, 03:09:00 PM

It my experience, it is relatively easy to make THF and water separate by the addition of some conc. NaCl and extracting with diethyl ether.

Title: In my experience, THF is often to be used in...
Post by: fanofshulgin on March 22, 2004, 04:00:00 PM

In my experience, THF is often to be used in preference to ether...since it has a higher BP and thus less likely to bump in case of rapid reaction.  THF and diethyl ether are virtually always interchangeable solvents.  Rhodium is 100% correct, dont worry about the THF/water solubility problem - as long as you saturate with salt and do three extractions you should be able to achieve close to theoretical recovery.

Fan of Shulgin

Title: Perhaps even the addition of sat. aq.
Post by: Bandil on March 22, 2004, 05:05:00 PM

Perhaps even the addition of sat. aq. NH₄Cl will cause the water and THF to separate?

Title: Any salt will do
Post by: Rhodium on March 22, 2004, 05:44:00 PM

Definitely. The thing working its magic is the increased polarity of the aqueous layer by any dissolved salt, which makes it too polar for the THF to want stay in the same phase.