Author Topic: benzaldehydes to phenylacetones  (Read 14051 times)

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Barium

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Hi Beaker It could very well be the reason for ...
« Reply #20 on: July 24, 2002, 07:04:00 AM »
Hi Beaker

It could very well be the reason for the lower yields. But I suspect that the very short reaction time is the primary cause. I intentionally shortened the reaction time just because I did not have the time to let it run full time. And the test verified that ketone could be made this way as well.

No did not check the toluene for substrate.

I will dig myself down in this reaction when a little more time is avalible. Imaging to be able to run this reaction in just MeOH without PTC....  ;D

Barium

  • Guest
Check this out!!
« Reply #21 on: July 31, 2002, 03:58:00 AM »
To a three-necked 3000ml rb flask with a stir bar add 166g (1mol) 2,5-dimethoxybenzaldehyde, 15g Aliquat 336, 159g (1.3mol, 139.5ml) methyl 2-chloropropionate, 500ml toluene and 200ml MeOH .With a cold water bath the temperature is brought down to 10-15 deg C. 60g solid NaOH is added in portions of 2-4g over two hours while not allowing the temperature to rise over 15 deg C.

Do not get to brave while adding the hydroxide because the temperature can rise very quick, and you do not want to mop up the haloester from the floor and ceiling – trust me.
When about about 30g NaOH has been added the solution becomes very thick from some precipitate but this will gradually dissolve again. If it becomes too thick to be properly stirred add some more MeOH.

When all NaOH has been added allow the solution to stir for another two hours at room temp.
Then add a pre-made solution of 100g NaOH in 450ml MeOH dropwise during 2 hours while keeping the temperature at 20-30 deg C. Keep it stirring at room temp for another 4 hours and the let it stand over night. The next day the solution will be very thick from precipitated crystals. Add 500ml water and the crystals will dissolve. Separate the two layers and extract the organic layer with another 500ml water. The toluene layer can now be discarged.

To the combined aqueous extracts conc HCl is added until pH 2.5-3 is reached. This will cause a yellow oil to fall out. Allow the acid solution to stir for one hour at room temp, add solid NaCl (enough to saturate the solution) and 500ml toluene and stir for 10 minutes.
Separate the layers and extract the aqueous phase once more with 250ml toluene. Wash the combined toluene phases once with saturated NaHCO3 solution, dry with MgSO4 and remove the toluene by distillation. This leaves 2,5-dimethoxyphenylacetone as a yellow oil.

Yield: 152g (0.78mol) 2,5-dimethoxyphenylacetone

Rhodium

  • Guest
Great - but what about distillation of the ...
« Reply #22 on: July 31, 2002, 11:17:00 AM »
Great - but what about distillation of the ketone? What is the isolated yield after that, and what is the boiling point of 2,5-dimethoxyphenyl-2-propanone?

Barium

  • Guest
I´ve taken my old friend the oilpump to the ...
« Reply #23 on: August 01, 2002, 02:59:00 AM »
I´ve taken my old friend the oilpump to the graveyard. All I have left is the teflon membrane pump used for my rotovap system. This pump is not good enough to perform vac distillations of ketones in my opinion. In a short while I´ll get a new oil pump then you´ll get more data.

Bwiti

  • Guest
Methyl 2-Chloropropionate
« Reply #24 on: August 02, 2002, 11:26:00 PM »
Anyone know any patent #'s or synths for the methyl 2-chloropropionate?

Love my country, fear my government.

Rhodium

  • Guest
UTFSE for chloropropionate/bromopropionate/halopro...
« Reply #25 on: August 02, 2002, 11:55:00 PM »
UTFSE for chloropropionate/bromopropionate/halopropionate, it has been mentioned before in another context. Then it is just an easy esterification, you can use the procedure in

https://www.thevespiary.org/rhodium/Rhodium/chemistry/2ch.darzen.html

for methyl 2-chloroacetate.

Precursor2112

  • Guest
My first novel post
« Reply #26 on: August 13, 2002, 02:03:00 PM »
I was happy just to be able to locate 2,5,dmb.

Now, Barium, your telling me nothing has to blow up and I won't have to change indentities 5 times (radioactive precursors)?

Barium if you ever need rare blood or use of a kidney...

Dude, my life just got WAY more interesting...

Thank you and thank you hive!

The sky was the color of television tuned to a dead channel.

GC_MS

  • Guest
Darzens patents
« Reply #27 on: August 13, 2002, 11:07:00 PM »
I found some semi-interesting patents by George Darzens for the reaction named after him. It is not exactly the same as what has been documented by Barium, i.e. synthesis of phenylaceton derivatives from benzaldehydes, but it could be useful for bees who like to experiment with amphetamine analogues. See for yourself  ;) :

-

Patent DE174279

- Verfahren zur Darstellung von disubstituierten glycidsaeuren der allgemeinen Formel [...]
-

Patent DE174239

- Verfahren zur Darstellung von Aldehyden der allgemeinen formel [...]

Doped(TM) since 19.... euhm... a long time  :)

Tricky

  • Guest
?
« Reply #28 on: November 12, 2002, 11:21:00 PM »
Barium or somebee else I've just to ask.
Have you ever tryed this rxn with non-substituted benzaldehyde? Does it works? If yes, how about rate of yield? Or maybe it has some other conditions?
Pliz, if it's not so complicated for you, confide with this magic with me  :)
I'll be very grateful  :) !

Wanna make laugh the GOD? - Tell him about your plans.

Barium

  • Guest
Final touch
« Reply #29 on: November 14, 2002, 08:20:00 AM »
I´ve made quite a few phenylacetones with this method now, and finally I´ve got a nice overall method.

1 mol of your favourite benzaldehyde
1.1 mol methyl or ethyl 2-chloropropionate
1.5 mol sodium methoxide, preferebly as the commercially avalible and dirt cheap 30% soln in MeOH.
Toluene, about 200-250 ml/mol benzaldehyde. Make sure the toluene is dry.

Add the toluene, benzaldehyde and haloester to a rb flask equipped with a mag stirbar, thermometer and a addition funnel. With cooling, add the sodium methoxide solution dropwise at a rate which keeps the reaction temperature between 10 to 15°C. When the addition is over allow the mixture to stir at room temp for one hour.
The toluene solution of the glycidic ester is now poured into 1 mol NaOH, as a 5% aqueous solution, and the mixture heated to 70-75°C for 60 minutes to hydrolyze the glycidic ester. The toluene layer is then separated from the aqueous layer. The sodium salt of the glycidic acid can now be isolated by concentration of the aqueous solution to about one third of the original volume and cooling to 10°C, filtration and washing with cold MeOH affords the salt in a quite pure form.

The phenylacetone is generated by heating the previous alkaline solution of the sodium salt of the glycidic acid to 90°C, and acidifying to pH 5.5 with either acetic acid or hydrochloric acid. A vigourous evolution of carbon dioxide starts immediately upon addition of acid. The slightly acidic solution is kept at 90°C for approximately one hour, or about 10 minutes after the carbon dioxide evolution has ceased. The solution is then cooled to room temperature, the pH raised to 8, and the ketone extracted with ether, DCM or toluene.

Catalytic hydrogenation freak

Tricky

  • Guest
Wow!!!
« Reply #30 on: November 14, 2002, 08:40:00 AM »
Double wow!  :)
Many thanx, Barium.
Henry condensation is sux!

I'm your great fan  :)

Make Drugs, not War!

Cyrax

  • Guest
Barium, what is the P2P yield?
« Reply #31 on: November 15, 2002, 04:01:00 AM »
Barium, what is the P2P yield?

Barium

  • Guest
I do not know
« Reply #32 on: November 15, 2002, 04:36:00 AM »
I won´t be able to try it until my license drops in  :P

Catalytic hydrogenation freak

Hellowin

  • Guest
Thank !
« Reply #33 on: November 16, 2002, 09:29:00 AM »
Possible to replace methyl 2-chloropropionate
for Methyl (Ethyl,Butyl,) Chloroacetate in metod with phenylacetone ?



Rhodium

  • Guest
If you do that, the product will instead be the ...
« Reply #34 on: November 16, 2002, 01:35:00 PM »
If you do that, the product will instead be the phenylacetaldehyde, which depending on structure might polymerize (or not).

See

Patent US5057624

for a method.

Ritter

  • Guest
Check out that patent!!!!
« Reply #35 on: November 18, 2002, 07:35:00 PM »
Everyone!!!

Please examine the patent quoted by Rhodium above:

Patent US5057624


That patent contains some amazing, possibly revolutionary information!  Phenylacetaldehydes are aminated with AQUEOUS (30 & 40% soln) methylamine and aq. solutions of NaBH4.  Amazingly enough, that patent may hold the key to the Hives next revolutionary technique- A LaBTop style borohydride MDMA synth from simple, easy to make methylamine solution rather than the scrupulously anhydrous conditions called for by the Masters(LaBTop) original technique!!!  Although it isn't that difficult to run the procedure as described by LaBTop, it would tremendously simplify things if the NaBH4 could be added dropwise as an aq. soln rather than slowly adding the powdered solid reagent.  Comments?

Barium

  • Guest
Ahem!!
« Reply #36 on: December 09, 2002, 06:19:00 AM »
It has already been done  ;)  

Post 328680

(Barium: "A really wet reductive alkylation", Novel Discourse)


Catalytic hydrogenation freak

Barium

  • Guest
I wonder....
« Reply #37 on: December 09, 2002, 06:29:00 AM »
what the result would be if sodium methoxide is substituted for a strongly alkaline ion exchange resin? Dry sodium hydroxide gives decent results, 50% aq. sodium hydroxide/PTC gives so so results. The less then great yields with sodium hydroxide is most likely due to the fact that the hydroxide saponifies some of the halo ester before it has a chance to form a carbanion. Could this be prevented with the use of a dry alkaline ion exchange resin?
If so, the resin is regenerated very easily with 5-10% aq NaOH, washing with water until neutral and drying.

Comments..



Catalytic hydrogenation freak

Organikum

  • Guest
substituted hydroxyphenylacetone
« Reply #38 on: December 10, 2002, 11:52:00 AM »
Perhaps I am wrong, but I am very sure most of these reactions can easily be done by a biotransformation utilizing a system of active fermenting saccharomyces cervesiae or candida utilis with a carbon source, essential salts and coenzymes in water. The addition of acetaldehyde as hydrogen acceptor gives relevant higher yields. Yields >70% on benzaldehyde can be stated in a system transforming unsubstituted benzaldehyde to hydroxyphenylacetone. The reaction time is between 8 and 10 hours, the reaction itself is carried out in a usual fermenter whereby aeration seems to be a main factor. Literature also states that the oxygen masstransfer limits the reaction. Procedures for substituted benzaldehydes are to find in several patents and articles, this is a old hat to say it in short terms. The furtheron processing of the hydroxyphenylacetones is described in many variations including AL/Hg, Nickel catalyst, noble metal catalyst, with aqueous methylamine, with methylamine.HCL.... I can´t remember a variation not described.

So this yields hydroxyphenylacetones a dehydroxylation will be necessary for many wanted compounds. There can be no doubt that masterhydrogenators will solve this problem in one pot, as rumors go that complete dilletants have done this already.

but this is sure not feasible anyhow and wellknown to those skilled in the art.
I will troll back to crystal....


ORGY

now or never

Organikum

  • Guest
plain benzaldehyde to hydroxyphenylacetone
« Reply #39 on: December 11, 2002, 10:10:00 AM »
How benzaldehyde is transformed to hydroxyphenylacetone:

To a 4 liter mixture containing sterile tap water, 400 gram molasses and 2000 ml brewers wort at 32°C in a usual fermenter 250 gram wet bakers yeast were given. Fermentation started. After one hour 3 gram MgSO4, 8 gram KH2PO4 and 20 gram (NH4)2PO4 were added and ph was adjusted at 4,7 by adding diluted H3PO4. This was allowed to cool down to 25°C. 35ml benzaldehyde in EtOH were added followed by 40 ml acetaldehyde in H2O. Two droppers were installed to drop in 40 ml benzaldehyde and 50 ml acetaldehyde during the next 4 hours. The fermentor was aerated and stirred during the whole procedure.
After 8 hours the yeast was filtered out and the water extracted with petrolether using a perforator. The extraction lasted 12 hours then the petrolether was boiled away and collected for reuse. The remaining sluggish brownish liquid substance, about 130 ml was vacuum distilled and the fraction coming over between 120° to 150°C @ 18 torr was collected. It was about 80 ml which were processed further by an Al/Hg reductive alkylation shameless copied from MaDMAx. Thanks Max! The result of 25 gram ephedrine is mostly to blame on slappy handling, low experience, not éxtracting the yeast and 47.123 more small mistakes adding up. But for it was l-ephedrine, (TLC comparism to a probably clean sample, melting point, taste...) the reaction before has to have produced hydroxyphenylacetone and that was what was to proove.  It was the first run, a "proove of principle" and for this it was more than a success.

Important is heavy aeration with sterile air and permanent ph control with adjusting at <5,3.  Doing some test batches with yeast only is adviced. The whole procedure is certainly more related to brewing than to chemistry what is not negative IMHO. Later runs gave better results, literature claims >70% on benzaldehyde and I think that thats realistic, >50% should be reachable for everyone with some excercise.
This works on substituted benzaldehydes also as I believe also I don´t know if the dehydroxylation is a problem then. PPA is easily made and perhaps a more direct way to 4-MAR is possible? I don´t know.

ORGY

now or never