Sciencemadness Discussion Board

Catalytic transfer hydrogenation of cinnamic acid in alkaline aqueous medium using PdCl2/HCOOH/NaOH

greenivan - 1-7-2012 at 16:25

Catalytic transfer hydrogenation can be an effective method for reducing a variety of organic substrates, which avoids some of the technical and safety concerns associated with using compressed hydrogen gas. The heterogeneous mixture of Pd-C and ammonium formate in alcohol solvent has proven to be a particularly effective reagent in organic synthesis (Chan et al., 1997). Replacing organic solvents with water offers economic advantages, improves safety, reduces the environmental impact of the waste stream, and in combination with the development of catalytic processes offers great opportunities for `green' chemistry.' We have studied transfer hydrogenation in alkaline aqueous conditions as part of a broad investigation of noble metal-catalyzed reactions of organic substrates in water. Herein, we report a convenient, effective method for reducing unsaturated carboxylic acids using the nonpyrophoric catalyst palladium(II)chloride, formic acid, and sodium hydroxide base in water.

The reduction of cinnamic acid was carried out using 10 mol% PdCl2 and 4 equivalents of hydrogen donor, in 2.5 M aqueous NaOH solution, heated to 65°C for 16 h. A series of potential hydrogen donors was investigated, from which formic acid was the most effective (yield of hydrocinnamic acid was 98%), followed in decreasing order of effectiveness by: glyoxylic acid (80%), gluconic acid (35%), N-(2-hydroxyethyl)ethylenediaminetriacetic acid (20%), glycolic acid (20%), and formaldehyde (5%). Formaldehyde is known to produce hydrogen under alkaline aqueous conditions, but was ineffective for the reduction under these conditions. The reaction was also successful using varying hydroxide concentrations ranging from 0.5 to 5 M; however, no reduction was evident when 2.5 M Na2CO3 was used as base (Tjiasmanto & Takigawa, 2011).

In summary, PdCl2 is an effective catalyst for transfer hydrogenations using formic acid in alkaline aqueous media. This procedure is advantageous because no organic solvent is required, the reagents are inexpensive, and the catalyst is nonpyrophoric. These reaction conditions should be suitable for the reduction of a wide variety of organic substrates, and offers an economical, safe, and environmentally benign alternative to available procedures.

Typical procedure: To a stirred solution of cinnamic acid (50 mg, 0.33 mmol) in 2.5 M aqueous NaOH (4 mL) was added PdCl2 (6.0 mg, 0.025 mmol). Formic acid (50 uL, 1.3 mmol) was added dropwise, then heated to 65°C for 16 h. The reaction mixture was neutralized with 2 M HCI, extracted with diethyl ether (2x5 mL), washed with water (10 mL), and dried (Na2SO4). The product was then purified by a short column of silica gel eluted with 25% ethyl acetate in hexanes. Removal of solvent in vacuo gave hydrocinnamic acid (50 mg, 98% yield).


Sources:
Tetrahedron Letters 41, 7847-7849

chemrox - 1-7-2012 at 16:47

It's nice to know that "tried and true" applied in the use of formic acid here. Is it possible that formaldehyde engaged a competing reaction with the double bond? I applaud the use of aqueous conditions and appreciate the good write-up.

madcedar - 1-7-2012 at 19:53

Nice find. Won't the PdCl2 get reduced to Pd?... not that it matters because in that case you can just use the Pd for the next reaction run.

jon - 1-7-2012 at 20:46

love the cth but therre wsa this particular substrate that required very specific conditions for it's reduction the only literature ex reads


analog 2
(des-chloroloperamide)
was synthesized by hydrogenation of 1 (loperamide) (514 mg) in ethanol 20 ml, containing triethylamine (.4ml) and 50 mg's of 10% pd/c for 24 hr. to yeild 44% (196 mg) after recrystalization (i think it's isopropanol/acetone)


another thing heat in the range of 50-65C is best in this case if it hits 80 the tert alcohol gets it.
but the lit reads 2 hours for some substrates but you were wise to run it 16 hours.
some of the substrates that have nucleophlillic groups tie up that pd and slow the reaction down.
it's first order so dependdant on conc of formate as long as it's no lower than 1 mol% no problems.
have fun with that hydrocinnamic acid.

but i suspect cth is better it's a work in progress.
it's not as easy as cinnamic acid though it takes basic conditions to get this to work so you have to work with the base you can use any of the formate donors.
they compete for binding at pd so you use exactly 2 moles ammonium formate if you use sodium formate and water use 3 moles of water.
methanol is no joy,
ethanol and ipa, joy!


[Edited on 2-7-2012 by jon]

DrNoiZeZ - 2-7-2012 at 04:49

Good work

I never did it that way, I use Pd/C 5% and NaBH4 in MeOH / THF with very good results and the catalist is very easy to use again. Next time I`ll try that way.

jon - 2-7-2012 at 12:15

strange why would you need a catalyst when you hav a already source of hydride solvated in methanol?
it's news to me.
please explain.

Nicodem - 2-7-2012 at 12:31

Quote: Originally posted by chemrox  
It's nice to know that "tried and true" applied in the use of formic acid here. Is it possible that formaldehyde engaged a competing reaction with the double bond? I applaud the use of aqueous conditions and appreciate the good write-up.

It is not his work. He copy-pasted everything in his post from that Tetrahedron letters article, except for the last two lines. I don't know what purpose such a clumsy pseudoplagiarism could have. I would have thought he simply forgot to put the text in quotations, but then even that is doubtful given the post is introducing no discussion and contains no questions. We already had such wannabe-autistic new members who would post random copypasta from articles without any point, but I never figured what their purpose is.

DrNoiZeZ - 2-7-2012 at 14:28

To Jon
Yes, I know that but the NaBH4 does not reduce the nitro group on alcanes and using Pd/C the reduction is very easy and the yields are good. The references I dont have it anymore but I think there where some information on Rhodium but I dont remember where. the fact is that I was having trouble to find a method then I begin to try TCH and for me it is the choice for reduction. I never tried with formates or formic acid.

jon - 2-7-2012 at 14:32

oh so your forming a mixed hydride something similar to using nickel salts to make nickel hydrides in situ.
hand smacks forehead, hand hurts.
same m.o., thanks for jogging my memory.


i seem to remember CTH on nitropropenes made the hydroxyl amines with Pd/C and potassium formate.
MDOH for example was made like that.
that was "barium's" work.
seems to imply a litttle more time heat whatever would give the amines.


[Edited on 2-7-2012 by jon]

[Edited on 2-7-2012 by jon]

DrNoiZeZ - 2-7-2012 at 14:35

I didnt know the work was already published, sorry if someone tried to plagiate, I think it was just a missunderstanding

DrNoiZeZ - 2-7-2012 at 14:40

sorry Jon I am not understanding what you are saying. I am only saying the the reduction works well that way and I am shure that it will not work on a nitropropene with NaBH4 alone (That will go to nitropropane only) so after that I use more NaBH4 and Pd and for me it is OK. Are you triing to say that it is not a CTH reduction?

jon - 2-7-2012 at 15:02

i apologize for my poor communication skills.
what i was saying was it is similar to another process where nickel chloride and sodium borohydride to reducce the double bond and the nitro group so the mecahnism was hydride transfer to nickel formining nickel hydride in-situ.
similar to what you are talking about same mechanism.
and it seems to be the preffered route for reduction of nitropropenes.

what i was also saying is that on the hive i seem to remember "barium" using Pd/C 10% and potassium formate on a nitropropene and getting incomplete reduction yeilding hydroxylaqmine which seemed to suggest that a little more time heat or other optimization would also make this a viable route.

DrNoiZeZ - 2-7-2012 at 15:12

Ok, we really agreed that. I remember to try with Nickel but it didnt work for me. the reduction of a nitropropene direct to amine is problematic thats why I did it two stages. You are right.

solo - 2-7-2012 at 15:13

Quote: Originally posted by Nicodem  
Quote: Originally posted by chemrox  
It's nice to know that "tried and true" applied in the use of formic acid here. Is it possible that formaldehyde engaged a competing reaction with the double bond? I applaud the use of aqueous conditions and appreciate the good write-up.

It is not his work. He copy-pasted everything in his post from that Tetrahedron letters article, except for the last two lines. I don't know what purpose such a clumsy pseudoplagiarism could have. I would have thought he simply forgot to put the text in quotations, but then even that is doubtful given the post is introducing no discussion and contains no questions. We already had such wannabe-autistic new members who would post random copypasta from articles without any point, but I never figured what their purpose is.


.....the is the article copied,

Pergamon Tetrahedron Letters 41 (2000) 7847–7849
Palladium-catalyzed transfer hydrogenation in alkaline aqueous medium
Jeffrey B. Arterburn,a,* Madhavi Pannala,a Anicele M. Gonzaleza and Rebecca M. Chamberlinb


http://144.206.159.178/ft/1010/29532/510078.pdf

jon - 2-7-2012 at 15:35
Quote:

we really agreed that. I remember to try with Nickel but it didnt work for me. the reduction of a nitropropene direct to amine is problematic thats why I did it two stages
.


i seem to remember the competing rates of polymerization and reduction are the main hinderance in direct reduction of nitro propenes.
the infamous "sky blue polymer"

madcedar - 2-7-2012 at 18:10

Thank you for the reference Solo and nice rant Nicodem, not your best buy still a good one. :)
Quote: Originally posted by solo  
Quote: Originally posted by Nicodem  
Quote: Originally posted by chemrox  
It's nice to know that "tried and true" applied in the use of formic acid here. Is it possible that formaldehyde engaged a competing reaction with the double bond? I applaud the use of aqueous conditions and appreciate the good write-up.

It is not his work. He copy-pasted everything in his post from that Tetrahedron letters article, except for the last two lines. I don't know what purpose such a clumsy pseudoplagiarism could have. I would have thought he simply forgot to put the text in quotations, but then even that is doubtful given the post is introducing no discussion and contains no questions. We already had such wannabe-autistic new members who would post random copypasta from articles without any point, but I never figured what their purpose is.


.....the is the article copied,

Pergamon Tetrahedron Letters 41 (2000) 7847–7849
Palladium-catalyzed transfer hydrogenation in alkaline aqueous medium
Jeffrey B. Arterburn,a,* Madhavi Pannala,a Anicele M. Gonzaleza and Rebecca M. Chamberlinb


http://144.206.159.178/ft/1010/29532/510078.pdf

greenivan - 5-7-2012 at 10:40

Quote: Originally posted by Nicodem  
Quote: Originally posted by chemrox  
It's nice to know that "tried and true" applied in the use of formic acid here. Is it possible that formaldehyde engaged a competing reaction with the double bond? I applaud the use of aqueous conditions and appreciate the good write-up.

It is not his work. He copy-pasted everything in his post from that Tetrahedron letters article, except for the last two lines. I don't know what purpose such a clumsy pseudoplagiarism could have. I would have thought he simply forgot to put the text in quotations, but then even that is doubtful given the post is introducing no discussion and contains no questions. We already had such wannabe-autistic new members who would post random copypasta from articles without any point, but I never figured what their purpose is.


really sorry, mod... i dont want to make any plagiarism so I wrote the source of the articles and I just privately think the article is nice to be shared..