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All 6 posts Subject: Acetone + Benzene -> P2P Please login to post Down

Rhodium
(Chief Bee)
11-26-02 18:54
No 383594
User Picture       Acetone + Benzene -> P2P

Check out https://www.rhodium.ws/pdf/archive/alpha-arylation.html

It is a review article about alpha-arylation of ketones, in other words methods which can be used to attach acetone to a benzene ring, forming phenylacetone (P2P). I don't have the time to chase all those references, but somebody else may be interested in doing that some rainy day?

slappy
(Hive Bee)
11-27-02 06:49
No 383819
      P2P's by Pd-catalyzed arylation of acetoacetates
(Rated as: excellent)

The yields are no good. You need to use a beta-ketoester as the acetone source, then decarboxylate.

That is why I present...

Synthesis of substituted Phenylacetone derivatives via Pd-catalysed alpha-Arylation of Acetoacetate esters.

The efficent large scale synthesis of Phenylacetone and it's derivatives can be accomplished from economical precursors via a Pd-catalysed coupling reaction, and subsequent decarboxylation. First, Methyl (or Ethyl) Acetoacetate is alpha-Arylated with an Aryl Halide (Ph-Br, Ph-I, Ph-OTf), to form 1-Carbomethoxy-Phenylacetone. This ester is then decarboxylated by boiling in dilute HCl, yielding P2P. The attractivness of this route is that it starts from cheap, commodity chemicals (Bromobenzene, Ethyl Acetoacetate, and tribasic Potassium Phosphate are less than $30/kg), low catalyst loading (1-2 mol% Pd), and high efficiancy (yield 80-90%).

The mechanism involves oxidative addition of Ar-X to the Pd center to give L_n(Ar)Pd-X (where L=1 or 2),which then coordinates to the enolate (formed by the beta-Ketoester and base, like K₃PO₄), and eliminates a mole of KX, giving L_n(Ar)Pd-Enolate, which couples the coordinated Aryl moiety, and reductivly eliminates.

Aryl Halide (1 eq) = R-Ph-Br, R-Ph-I, R-Ph-OTf
Alkyl Acetoacetate (1.2 eq)
Base (2 eq) = K₃PO₄
Pd pre-catalyst (1 mol%) = Pd(OAc)₂, Pd₂(dba)₃
Phosphine ligand (2.2 mol%) = PPh₃, P^tBu₃, PCy₃

Sutible solvents:
THF, Toluene, Dioxane

Reaction conditions:
10-48h at 70-100°C

Ref:

Buchwald et al., "Highly Active and Selective Catalysts for the Formation of a-Aryl Ketones", J. Am. Chem. Soc. 2000, 122, 1360-1370
Hartwig et al., "Transition metal-catalysed process for preparing alpha-arylated carbonyl containing compounds", Patent US6057456

java
(Hive Bee)
09-15-03 02:55
No 459112
      Re: Acetone + Benzene -> P2P"

slappy,..have you had a chance to run this procedure , if so can you walk it through as to the arylation, is this a reflux procedure , and then the step 2 with then decarboxylated with HCl with some boiling , how long whe will you know the process has ended....TLC?

If you can , a walk through would be appreciated......java

Note: I did get the reference reading you posted and will go through it to gain understanding

We're all in this world together,
http://www.chiapaslink.ukgateway.net/

Barium
(Heavyweight Chempion(eer))
09-15-03 07:44
No 459159
      The decarboxylation can easily be monitored by

The decarboxylation can easily be monitored by the gas evolution. Since a excess of HCl will be present all the CO₂ will be driven out of solution. If you want to be absolutely sure not to run it too long lead the CO₂ through a Ca(OH)₂ solution and stop the heating when no more CaCO₃ precipitates.

Isn't the arylation of the ester a example of a Heck coupling?

The Unworthy

Vitus_Verdegast
(Hive Bee)
09-15-03 14:40
No 459194
User Picture       Heck

It looks very similar to a Heck coupling, but I haven't seen that performed with an ester before, I thought it was mainly used on alkenes.

A Dream Within A Dream (http://www.poedecoder.com/Qrisse/works/dreamw.html)

java
(Hive Bee)
09-16-03 16:54
No 459422
      Heck Reaction on Functional groups..
(Rated as: good read)

(Excerps taken from March's 5th edition.....pg. 930 Sec. 14-9)

Arylation and Alkylation of Alkenes by Organopalladium compounds : The Heck Reaction

R2C=CH2 +"ArPdX"------>R2C=CH-Ar

"the Heck Reaction is not limited to activated substrates. The substrate can be a simple alkene , or it can contain a variety of functional groups,such as ester, ether,(348,349), carboxylic acids, phenolic or cyano groups.(350) It can also be a diene.(351) Primary and sedondary allylic alcohols (and even non -allylic unsaturated alcohols (352) ) give aldehydes or ketones that are products of double -bond migration,(353)..."

e.g. CH2=CH-CH2OH-----PhPdCl------>PhCH2CH2CHO

References.

348.For a review pertaining to enol ethers, see Daves Jr.,G.D. Adv. Met.-Org. Chem., 1991,2,59
349. Larhead, M,; Hallberg, A. J.Org.Chem.,1996,61,9582
350.for a review of cases where the alkenen contains an heteroatom, see Daves Jr., G.D.; Hallberg, A. Chem. Rev. 1989,89,1433
351.Jeffrey,T. Tetrahedron Lett., 1991,33,1989
352.Larock, R, C,; Leung, W.; Stolz-Dunn, S.Tetrahedral Lett..1989,30,6629
353.See, for example, Melpolder, J.P.;Heck, R.F.J. Org. Chem.,1976,41,265Chalk, A.J.; Magennis, S.A. J. Org. Chem., 1976,41,273,...1206

Note:... so based on the above text and example then......

CH3-CH(OH)-CH3------>PhPdCl----->PhCH2-CO-CH3

should also be possible.....java

We're all in this world together,
http://www.chiapaslink.ukgateway.net/

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	All 6 posts		Subject: Acetone + Benzene -> P2P		Please login to post		Down


		Rhodium (Chief Bee) 11-26-02 18:54 No 383594				Acetone + Benzene -> P2P
						Check out https://www.rhodium.ws/pdf/archive/alpha-arylation.html It is a review article about alpha-arylation of ketones, in other words methods which can be used to attach acetone to a benzene ring, forming phenylacetone (P2P). I don't have the time to chase all those references, but somebody else may be interested in doing that some rainy day?



		slappy (Hive Bee) 11-27-02 06:49 No 383819				P2P's by Pd-catalyzed arylation of acetoacetates (Rated as: excellent)
						The yields are no good. You need to use a beta-ketoester as the acetone source, then decarboxylate. That is why I present... *Synthesis of substituted Phenylacetone derivatives via Pd-catalysed alpha-Arylation of Acetoacetate esters.* The efficent large scale synthesis of Phenylacetone and it's derivatives can be accomplished from economical precursors via a Pd-catalysed coupling reaction, and subsequent decarboxylation. First, Methyl (or Ethyl) Acetoacetate is alpha-Arylated with an Aryl Halide (Ph-Br, Ph-I, Ph-OTf), to form 1-Carbomethoxy-Phenylacetone. This ester is then decarboxylated by boiling in dilute HCl, yielding P2P. The attractivness of this route is that it starts from cheap, commodity chemicals (Bromobenzene, Ethyl Acetoacetate, and tribasic Potassium Phosphate are less than $30/kg), low catalyst loading (1-2 mol% Pd), and high efficiancy (yield 80-90%). The mechanism involves oxidative addition of Ar-X to the Pd center to give L_n(Ar)Pd-X (where L=1 or 2),which then coordinates to the enolate (formed by the beta-Ketoester and base, like K₃PO₄), and eliminates a mole of KX, giving L_n(Ar)Pd-Enolate, which couples the coordinated Aryl moiety, and reductivly eliminates. Aryl Halide (1 eq) = R-Ph-Br, R-Ph-I, R-Ph-OTf Alkyl Acetoacetate (1.2 eq) Base (2 eq) = K₃PO₄ Pd pre-catalyst (1 mol%) = Pd(OAc)₂, Pd₂(dba)₃ Phosphine ligand (2.2 mol%) = PPh₃, P^tBu₃, PCy₃ Sutible solvents: THF, Toluene, Dioxane Reaction conditions: 10-48h at 70-100°C Ref: Buchwald et al., "Highly Active and Selective Catalysts for the Formation of a-Aryl Ketones", J. Am. Chem. Soc. 2000, 122, 1360-1370 Hartwig et al., "Transition metal-catalysed process for preparing alpha-arylated carbonyl containing compounds", Patent US6057456



		java (Hive Bee) 09-15-03 02:55 No 459112				Re: Acetone + Benzene -> P2P"
						slappy,..have you had a chance to run this procedure , if so can you walk it through as to the arylation, is this a reflux procedure , and then the step 2 with then decarboxylated with HCl with some boiling , how long whe will you know the process has ended....TLC? If you can , a walk through would be appreciated......java Note: I did get the reference reading you posted and will go through it to gain understanding We're all in this world together, http://www.chiapaslink.ukgateway.net/



		Barium (Heavyweight Chempion(eer)) 09-15-03 07:44 No 459159				The decarboxylation can easily be monitored by
						The decarboxylation can easily be monitored by the gas evolution. Since a excess of HCl will be present all the CO₂ will be driven out of solution. If you want to be absolutely sure not to run it too long lead the CO₂ through a Ca(OH)₂ solution and stop the heating when no more CaCO₃ precipitates. Isn't the arylation of the ester a example of a Heck coupling? The Unworthy



		Vitus_Verdegast (Hive Bee) 09-15-03 14:40 No 459194				Heck
						It looks very similar to a Heck coupling, but I haven't seen that performed with an ester before, I thought it was mainly used on alkenes. A Dream Within A Dream (http://www.poedecoder.com/Qrisse/works/dreamw.html)



		java (Hive Bee) 09-16-03 16:54 No 459422				Heck Reaction on Functional groups.. (Rated as: good read)
						(Excerps taken from March's 5th edition.....pg. 930 Sec. 14-9) Arylation and Alkylation of Alkenes by Organopalladium compounds : The Heck Reaction R2C=CH2 +"ArPdX"------>R2C=CH-Ar "the Heck Reaction is not limited to activated substrates. The substrate can be a simple alkene , or it can contain a variety of functional groups,such as ester, ether,(348,349), carboxylic acids, phenolic or cyano groups.(350) It can also be a diene.(351) Primary and sedondary allylic alcohols (and even non -allylic unsaturated alcohols (352) ) give aldehydes or ketones that are products of double -bond migration,(353)..." e.g. CH2=CH-CH2OH-----PhPdCl------>PhCH2CH2CHO References. 348.For a review pertaining to enol ethers, see Daves Jr.,G.D. Adv. Met.-Org. Chem., 1991,2,59 349. Larhead, M,; Hallberg, A. J.Org.Chem.,1996,61,9582 350.for a review of cases where the alkenen contains an heteroatom, see Daves Jr., G.D.; Hallberg, A. Chem. Rev. 1989,89,1433 351.Jeffrey,T. Tetrahedron Lett., 1991,33,1989 352.Larock, R, C,; Leung, W.; Stolz-Dunn, S.Tetrahedral Lett..1989,30,6629 353.See, for example, Melpolder, J.P.;Heck, R.F.J. Org. Chem.,1976,41,265Chalk, A.J.; Magennis, S.A. J. Org. Chem., 1976,41,273,...1206 Note:... so based on the above text and example then...... CH3-CH(OH)-CH3------>PhPdCl----->PhCH2-CO-CH3 should also be possible.....java We're all in this world together, http://www.chiapaslink.ukgateway.net/

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