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Author: Subject: Synthesis of 3-(p-Hydroxyphenyl)-2-Butanone "raspberry ketone"
Klute
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[*] posted on 5-10-2008 at 10:20


Good news!


I have tried out the atm hydrogenation of dehydrorheosmin over Pd/C, using 25% mol/mol AcONa as an additive, in AcOEt, and after 14H all the unsaturated ketone was reduced to the saturate dketone, without any traces of the alcohol!

I'm unsure if it is this substrate that is much more ressitant to reduction of the carbonyl, or if using sodium acetate is very effective as suppressing 1,2-hydrogenation, but the reduction was text book perfect: regular H2 absorption, and theoritical amount consumed.

Using 1:1 AcOEt:Pet ether as an eluant proved to give a superior seperation than with the eluant used during the Zn reduction. I am unsure of which side-products are formed during the reduction, but I'm pretty sure Zn/AcOH can't be used as a preparative procedure for phenolic butanones..

Sorry, still no photos I haven't got the camera issu dealt with yet..

Workup was simple: filtration of the catalyst and suspended AcONa, washing on the colorless filtrate, followed by drying and removal of the solvent..

The isolated product smells much nicer than the Zn reduction product! Much more subtle, "natural" aroma.

I can't wait to try the NiB hydrogeantion on the substrate. Even if it is clear than Pd/C is an ideal catalyst for such hydrogeantion, it si quite expensive and not always accesable. A cheap, easily made catalyst would really be usefull to many.




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[*] posted on 5-10-2008 at 23:30


Quote:
Originally posted by Klute
I'm unsure if it is this substrate that is much more ressitant to reduction of the carbonyl, or if using sodium acetate is very effective as suppressing 1,2-hydrogenation, but the reduction was text book perfect: regular H2 absorption, and theoritical amount consumed.

The aliphatic ketone carbonyl is not reducible using Pd-C (at least not at the usual conditions), with or without additives such as you used. In conjugated ketones it is normal that only the double bond gets reduced. Conjugated double bonds, particularly such conjugated with electron withdrawing groups like in your case, are considerably slower to reduce than isolated double bonds. Actually, isolated double bonds reduce in matter of minutes using couple of mol% 5% Pd-C at 1 atm. Moderately electron rich double bonds conjugated with the benzene ring (aka styrenes) also reduce quite fast.

Thanks for sharing your experience with Cu/SiO2 catalyst. I'm looking forward to read about your experiments using nickel boride based catalysts.




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[*] posted on 6-10-2008 at 02:07


Well, when reducing dehydrozingerone, at least 5% saturated alcohol was formed using Pd/C and K2CO3 (which I neutralized after). The Chem Educ. article on Rheosmin also mention this. It seems dehydrorheosmin is much less prone to this.

One of the NiB article claimed 99% selectivity using Pd/C, which i doubt at first, but has now confirmed. They say NiB give sthe same selectivity, but with a much higher absorption rate, and reduction of the double-bond is doen in a matte rof minutes. Can't wait to get this started.




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[*] posted on 6-10-2008 at 02:43


That ref I gave over in the Cassione, using MVK in a Heck reaction, used Pd/TiO2 for both the Heck and the reduction of the C=C double bond, further suggesting that Pd is useful although perhaps not optimal time-wise for this class of reduction. I wonder if Pd/TiO2 would prove easier to reactivate than Pd/C.
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[*] posted on 8-10-2008 at 12:36


Ok, I just HAD to find a camera to take pictures of theses and show them to you guys... I have fallen in love of my Rheosmin and have been showinbg it to evryone I cross :)








96.6% Yield by H2/ Pd/C hydrogenation (actually I realized absorption was finished after 4h, as the theorical volume was 150mL! I guess the other 100mL were lost from small leaks or something. The absorption rate had greatly diminished afetr 150mL mark...

Ideal TLC eluant: 50:50 AcOEt: Pet ether. Will get Rf if someone wants them (saturated ketone higher than the unsaturated one, no traces of alcohol or other by-products!)

Let's hope NiB can do as good! I feel like making dozen grams of the stuff, my room smells beautifull :) Pretty strangely, the nice crystals smell much less than the crude powder, before recrystallization.




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[*] posted on 6-2-2009 at 03:44


I've stumbled on a pretty interesting article, detailing the use of NiB supported on silica gel to selectivily reduce cyclopentadiene to cyclopentene...

NiB/SiO2 is prepared by impregneting NaBH4 on silica gel, then adding this silica to a solution of NiCl2, forming amorphous NiB on the support. Good selectivities are reported for the reduction of cyclopentadiene, and I assume the NiB posses the same reactivity as collodial NiB towards unsaturated ketones, and would then offer a good alternative to collodial borides and their tedious workup..

EDIT: attached article


Selective hydrogenation of cyclopentadiene to cyclopentene
Wang et al.
Applied Catalysis A; 163, 101-109 (1997)

Abstract
An amorphous NiB/SiO2 catalyst, with a large specific surface area, was prepared by a reductive-impregnation method. The
selective hydrogenation of cyclopentadiene to cyclopentene was carried out in a continuous flow fix-bed reactor at
atmospheric pressure and with 10 g g cat -I h -l of cyclopentadiene feed. The catalyst showed high selectivity and stability.
Cyclopentene was obtained in 96--100% yield at complete conversion of cyclopentadiene at temperatures ranging from 80°C
to 200°C and no significant decrease of the activity was observed during the reaction period of 500 h. The catalyst sample was
characterized by ICP, XRD, DSC, SEM, XPS, BET and 02 adsorption. XRD measurement revealed that the amorphous state
was kept after catalytic reaction. Differential kinetic study showed that the hydrogenation proceeded according to a Rideal-
Eley mechanism.

Keywords:
Supported amorphous alloy; Nickel-boron alloy; Cyclopentadiene hydrogenation; Catalytic activity; Differential
kinetics

[Edited on 6-2-2009 by Klute]

Attachment: NiB_SiO2.pdf (590kB)
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[*] posted on 6-2-2009 at 06:59


Yes i am !
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[*] posted on 6-2-2009 at 12:19


Klute you have some amazingly pretty crystals there! Nice work and great yield!



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[*] posted on 6-2-2009 at 12:30


Thank you :)

They really are part of my favourites! Both the smell and the apparence!




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[*] posted on 30-4-2009 at 14:40


Recently I have got few grams of 10% Pd/alumina, so I have tried hydrogenation of benzylideneacetone. Unfortunately, suspension of catalyst (0,3g) in 30g unsaturated ketone+50 cm3 of toluene does not want to "eat" hydrogen (under almost atmospheric pressure and 30-40 C). I also tried ethyl acetate instead of toluene - results the same.
This Pd/alumina is a little old - is it possible that it needs to be activated somehow ? I mean H2 stream nad ~300 C....
I do not know, I am not familiar with hydrogenations on Pd :(
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[*] posted on 30-4-2009 at 23:12


Klute has reported in this thread that formate can liven up an old catalyst. Can't say about the solvent, but I would stick to GAA for starters.
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[*] posted on 1-5-2009 at 07:12


The activity of the catalyst depends on how the metal has been deposited on the carrier. There are three types of deposition and the one suited for low pressure reactions is the eggshell type. The fact that alumina is the carrier makes it likely that you have an industrial catalyst which requires higher pressures, although there are eggshell types of catalysts using alumina as carrier.
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[*] posted on 3-5-2009 at 07:35


All I know is on the label: Koch-Light, 8874h Pd 10% on alumina, for lab use only.
I did reactivation in slow H2 stream at 320 C and hydrogenation takes place, but is very slow. I will try to increase overpressure from 100 to 200 mm of H2O.
ps. product smells nicer and nicer, strawberry-like and reminds me benzylmethyl ketone.
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[*] posted on 4-5-2009 at 00:14


I would try using CTH conditions, I requested a few articles on the subject lately, apparently ammonium formate gives excellent resultd for the selective reduction of the conjugated double bond, without producing any (or very little) alcohol. You could try adding some formate to a suspension of your catalyst and see if any gas is evolved, then try the reduction under CTH conditions in methanol. Good luck! Please let us know how it goes!



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[*] posted on 22-8-2009 at 12:51


Why not give sodium dithionite a try for the reduction of the double bond?

It works for isatylideneacetone, it might as well for your substrate. The procedure is so straightforward that it can't hurt giving it a try.



Tet. Lett. 49, 21 p 4741-4758 (1993)




Attachment: isatylideneacetones.pdf (1.8MB)
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[*] posted on 23-8-2009 at 13:35


Interesting, never thought of that. Could be worth a try!



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[*] posted on 11-9-2009 at 00:38


Maybe you could try a catalytic reduction with an iron catalyst:

catalytic amounts of [Fe(CN)5NH3]3- reducte in an excess of NH2OH oelfines without affecting carbonyl functionalities and aromatic rings

[Fe(CN)5NH3]3- can be prepared from [Fe(CN)5NO]2- (Nitroprusside-anion) with can be prepared from [Fe(CN)6]4-

seen at: http://pubs.acs.org/doi/abs/10.1021/jo800302v
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Klute
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[*] posted on 12-9-2009 at 10:43


Interesting alternative, but the preparation of the catalyst requires cyanide, which I do not have, and isn't specialy oTC.. But surely other ligands could work aswell..
I have started to interest myself to homogeneous catalysis, using avaible transition metals, like Cu, Fe, Ni, etc. Not alot of ligands are easily made at home, but there could be some viable paths.. I guess reduction-wise , Nickel complexes are the best candidates. If I could find a cheap source of ruthenium, I could try using some of teh catalysts I worked on recently, very active in CTH conditions..




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[*] posted on 12-9-2009 at 11:40


No, it does not require cyanide. Potassium ferrocyanide , K4Fe(CN)6.3H2O is very cheaply available from chemicals suppliers, is not suspious, and is not toxic. The cyanide is only slowly released when heating with a strong acid.

IIRC, the nitroprusside can be prepared by treating the ferrocyanide with nitric acid, but I don't know the exact procedure. Be warned, the nitroprusside is very toxic, at least it is when injected.
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[*] posted on 12-9-2009 at 12:17


other lingand no problem.... ;)

http://pubs.acs.org/doi/abs/10.1021/om050625b

but i think this one might be carcinogen and it need's (silght) overpressure... would prefer the [Fe(CN)5NH3]3- which possibly is not toxic at all since the toxic effekt of the [Fe(CN)5NO]2- is induced by the elimination of NO

I've tryed to make [Fe(CN)5NH3]3- some time ago (wanted to use it on dehydrozingerone) but instead of obtaining nice red crystals i obtained a brown slurry, if someone made this already i would be thankfully for some hints ^^
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[*] posted on 14-9-2009 at 06:36


Quote: Originally posted by Sydenhams chorea  
Why not give sodium dithionite a try for the reduction of the double bond?

It works for isatylideneacetone, it might as well for your substrate. The procedure is so straightforward that it can't hurt giving it a try.



Tet. Lett. 49, 21 p 4741-4758 (1993)


Interesting. However, that double bond is doubly alpha to carbonyls, and hence highly activated. Perhaps thiourea dioxide would be worth a test here.

EDIT: What am I thinking. Thiourea dioxide would reduce the ketone.

[Edited on 9-14-09 by UnintentionalChaos]




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[*] posted on 22-9-2009 at 23:03


Here's a little something for anyone interested. I ran the condensation of Vanillin with acetone (24h at room temperature), and recrystallized my product from 50:30 water:isopropanol. I then brought it over to school for use as a Michael acceptor in undergrad research. Here's a 400MHz proton NMR for you guys. Looks pretty good for all over the counter chemicals, huh? :P

The peak at 1.6ppm is water, but after running a blank of CDCl3 through the NMR, it's contamination of the chloroform, not the sample.

2.35ppm is the methyl ketone.

3.9ppm is the methoxy group

5.9ppm is the phenol hydrogen

The "triplet" with integration of 2 at 7.1ppm is the overlap of the singlet from the hydrogen in the 2-position on the ring with what I suspect is the 6 position hydrogen's doublet.

Unrelated, but has anyone seen what this stuff costs from Aldrich?

http://www.sigmaaldrich.com/catalog/ProductDetail.do?lang=en...

:o

[Edited on 9-23-09 by UnintentionalChaos]

vanillylNMR.jpg - 20kB




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[*] posted on 23-9-2009 at 02:52


Nice! Thanks for sharing! It's a rather clean spectra you've got there! Looks like the reaction is pretty selective and no impurirites remain after a single recrystallization..

Do you intend on reducing it to the butanone? A spectra of the butanone would be great too!




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[*] posted on 23-9-2009 at 04:57


Quote: Originally posted by Klute  
Nice! Thanks for sharing! It's a rather clean spectra you've got there! Looks like the reaction is pretty selective and no impurirites remain after a single recrystallization..

Do you intend on reducing it to the butanone? A spectra of the butanone would be great too!


I also have a carbon spectra for this one if you'd like and I forgot to mention that I took a m.p. with a thiele tube and got 126-128C.

Possibly over winter break when I'm at home, but not with this material. More than likely, it'll be O-methylated to shield the phenol, since we think the reaction we're studying proceeds by a radical mechanism and phenols are radical traps. I won't know until I try though.

I will hopefully prepare some of the 4-hydroxyphenyl variant and reduce it to rheosmin, which I can get spectra for.




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[*] posted on 23-1-2016 at 18:47


Thanks for Klute's thread, i learn a lot from here. And the pink colour must be the combination phenol and zn2+ . Maybe add EDTA solution can eliminate it.
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