09-27-02 10:37
No 361260
      Internal aryl alkenes from aryl ketones (WOW!)
(Rated as: excellent)

A Modified Clemmensen Reduction Procedure for Conversion of Aryl Ketones into Aryl Alkenes
G. A. Hiegel and Carney, John R.
Synthetic Communications, 26 (14), 2625-2531 (1996)

Here's a way to reduce aryl ketones (easily synthesized by way of the Friedel-Crafts acylation reaction) to internal aryl alkenes. 


Reduction of 1-Phenyl-butanone.  This procedure was used for all reactions reported in the table.  In a round bottom flask were placed 10.11 g (0.155 mol) of Zn dust, 0.498 g (1.84 mmol) of HgCl2, 10 mL of H2O, 0.5 mL of conc HCl, and a stir bar.  After 10 min of stirring, the liquid was decanted, and any lumps were broken up with a spatula.  To the flask were added 20 mL of 88% formic acid, 6 mL of 95% ethanol, and 2.0 mL (13.78 mmol) of 1-phenyl-1-butanone.  The mixture was refluxed and stirred for 1 h.  The liquid was decanted into a separatory funnel, and the residue stirred with 20 mL of H2O for 5 min.  The water was also added to the separatory funnel and the residue stirred with 20 mL of CH2Cl2 for 5 min.  The CH2Cl2 was used to extract the aqueous phase.  The residue was washed two more times with 20 mL each of CH2Cl2, and the CH2Cl2 was used to extract the aqueous phase each time.  The combined CH2Cl2 solution was washed with 1 N NaOH until the wash was basic (60 mL and 30 mL) and with sat. NaCl solution (60 mL) and dried over MgSO4.  After filtration and solvent removal, the residue was distilled using a Kugelrohr apparatus to give 1.46 g of product (80% yield based on the molecular weight of the alkene) (bath temp 113-121 C at 43 torr). The IR and NMR spectra were a good match for that of trans-1-phenyl-1-butene, and the NMR spectrum also showed peaks indicative of the presence of small amounts of cis-1-phenyl-1-butene, butylbenzene, and CH2Cl2.  Analysis by GC (10% Carbowax 20M) showed significant peaks at 0.54 min (1.3%), 1.7 min (7.2%), 2.3 min (10.1%), 3.4 min (80.5%).  The peaks at 0.54, 1.7, and 3.4 min correspond tothe retention times of CH3Cl2, butylbenzene, and trans-1-phenyl-1-butene, respectively.  The peaks at 2.3 and 3.4 min were collected by preparative GC.  The NMR of the peak at 2.3 min agreed eith that reported for cis-1-phenyl-1-butene, and the NMR of the peak at 3.4 min matched that of trans-1-phenyl-1-butene.

Here are the some of the more interesting segments of the article:

"Our modification of the Clemmensen procedure which gives the highest ratio of alkene to alkane and the highest isolated yields involves refluxing the ketone with amalgamated zinc in 88% formic acid and 95% ethanol for 1 h. Significant results are summarized in the Table.  Acetic acid could be used in place of formic acid, but replacement of phosphoric acid, ammonium chloride, or anilinium chloride resulted in a lower ratio of alkene or a very slow reaction.  Methanol as the cosolvent was about as effective as ethanol, but cylcohexane, benzene, t-butyl alcohol, dioxane, or no cosolvent gave a slightly lower ratio of alkene.  Zinc amalgamated in the usual manner was used for extraction during the work-up was used for most experiments and gave the best results.  When methylene chloride was used for extraction during the work-up instead of diethyl ether, the isolated yields were improved significantly.

"1-Phenyl-2-propanone and 2-octanone, both alkyl ketones, did not react appreciably under the mild conditions used for aromatic ketones. 1-Phenyl-1-ethanone was reduced to a 16:84 GC ratio of ehtyl benzene to styrene but a distilled yield of only 19% was obtained.  A H NMR of the undistilled sample showed the presence of a cyclopropyl group which is believed to be formed from a zinc-carbene intermediate (Zn=C) reacting with the alkene.

"Rearrangement of the same zinc-carbene intermediate accounts for eh formation of the alkene.  Under the milder Clemmensen reduction conditions used here, apparantly aryl ketones easily form the zinc-carbene intermediate, and rearrangement to the alken is normally the major reaction pathway."

Yeilds for valerophenone were 80.6% of the trans isomer and 10.1% of the cis isomer (80% overall yield)

I hope I interpreted this part right (in regard to the cis and trans thing):

Yields for propiophenone were 78.2% of the trans isomer and 13.5% of the cis isomer (80% overall yield) 

There's more interesting stuff about the standard Clemmensen reduction but my hands are tired of typing.

That's all for now, folks!!!
10-01-02 14:45
No 362906
      Correction . . .     


In the experimental section, it should be 1-phenyl-1-butanone NOT 1-phenyl-butanone.

And at the bottom of the page, it should read as follows:

Yields of 1-phenyl-1-pentene from valerophenone were 80.6% of the trans isomer and 10.1% of the cis isomer (80% overall yield)

Yields of 1-phenyl-propene (propenyl benzene) from propiophenone were 78.2% of the trans isomer and 13.5% of the cis isomer (80% overall yield) 

So, I guess there's absolutely no interest in commenting on this monumental find? Maybe you guys simply don't understand what it is you're reading.

See ya.
(Chief Bee)
10-01-02 17:39
No 362977
      I believe it is wonderful, and I rated it ...     

I believe it is wonderful, and I rated it accordingly. When I have the time I will publish it on my page, after coding it to HTML and adding illustrations.

I am afraid I just cannot comment on the actual synthesis any further until I have had the opportunity to try it out in practice on some neutral substrate, and with my current busyness that will probably take ages... frown
(Official Hive Translator)
10-02-02 04:04
No 363179
      Me too     

I too think that your find is fabulous, Regis!

Don't worry - this board is notorious for meeting the MOST excellent findings with silencesmile - don't know why, probably 'cause everybee is so astounded that they are unable to speaklaugh

Well, anyway, what you posted is really cool - once again, thanks!


(Hive Addict)
10-02-02 10:23
No 363285
      enlighten us please...     

 Some, (like me) who have not climbed far enough up the org chem mountain to appreciate what you've found, would seriously appreciate a reduction of the significance into terms we could understand...

  When I read this, looks like you could take a ketone, like mp2p and reductively aminate it in 80%+ yields?

Infinite Radiant Light - THKRA
(Chief Bee)
10-02-02 11:06
No 363301
      No, the use of this is that you with a single ...     

No, the use of this is that you with a single reaction can transform cheap propiophenones (phenyl ethyl ketone) to propenylbenzenes (which as you know are only an oxidation away from P2Ps).
(Hive Bee)
10-02-02 14:19
No 363388
      chems cheap     

Hey Rhodium, glad that they're cheap for you.  no so much here.  got any suggestions for cheap (or at least easy formations of propiophenones- aside from classic friedel crafts?)
(Chief Bee)
10-02-02 14:43
No 363397
      Yes, you can react benzene with propionic acid in ...     

Yes, you can react benzene with propionic acid in polyphosphoric acid in high yield, grignard between benzonitrile/EtMgBr etc. 2-Hydroxypropiophenones can be formed from phenylpropionates too.
(Hive Bee)
10-03-02 16:22
No 363920
      Polyphosphoric acid     

Where was that polyphosphoric acid synth?  Lugh?  ....
(Chief Bee)
10-03-02 17:18
No 363947
      polyphosphoric acid
(Rated as: good read)

But Aurelius, can't even you find the search button? wink "Polyphosphoric" gives only 50 hits.

From Merck:
Post 464602 (roger2003: "Polyphosphoric Acid", Chemistry Discourse)

From lugh:

Liebig's Ann 65 30, 387 (1845) & 118 99 (1861)
Ueber einige Metallverbindungen der Triphosphorsäure Rostock (1896)
Beitrag zur Kenntnis der Triphosphorsäure und ihrer Salze Berlin (1899)
Ueber die Einwirkung von Phenolen auf Pyro- und Orthophosphorsäurchlorid, Rostock (1896)
Ultraphosphate Leipzig (1912)
Stahl Eisen 28 675 (1908) & 31 2020 (1911)
Chem Ztg 47 195 (1923)
Zeit anorg Chem 12 444 (1896); 76 387 (1912); 77 1 (1912) &  78 95 (1912)
Compt Rend Trav Chim 19 (1849)
Jour Iron Steel Inst 84 ii, 126 (1911)
(Chief Bee)
01-26-04 04:44
No 484656
      Conversion of Aryl Ketones into Aryl Alkenes
(Rated as: good read)

A Modified Clemmensen Reduction Procedure for Conversion of Aryl Ketones into Aryl Alkenes
G. A. Hiegel and Carney, John R.
Synthetic Communications, 26(14), 2625-2531 (1996) (../rhodium/chemistry /arylketones2arylalkenes.html)

Aryl alkenes can be prepared from aryl ketones through reduction by refluxing with amalgamated zinc in a mixture of formic acid and ethanol.

From Post 361260 (Regis: "Internal aryl alkenes from aryl ketones (WOW!)", Novel Discourse)

The Hive - Clandestine Chemists Without Borders
(Chief Bee)
05-20-04 17:01
No 508503
      Organic Reactions: The Clemmensen Reduction
(Rated as: excellent)

The Clemmensen Reduction
Elmore L. Martin
Organic Reactions, Volume 1, Chapter 7, p. 155-200 (1942) (../rhodium/pdf /or.clemmensen.reduction.pdf)


Types Of Compounds Reduced By The Clemmensen Method
Aliphatic Aldehydes
Aromatic Aldehydes
Aliphatic and Alicyclic Ketones
Aliphatic-Aromatic Ketones
Aromatic Ketones
Keto Acids
α-Keto Acids
β-Keto Acids
γ-Keto Acids
Other Keto Acids
α,β-Unsaturated Carbonyl Compounds
The Reduction of Other Functional Groups by Amalgamated Zinc and Hydrochloric Acid

Experimental Procedures
General Discussion
Preparation of Zinc Amalgam
The Clemmensen Reduction in the Absence of an Organic Solvent (Method I)
Reduction of β-(p-Tolyl)-propionic Acid
Reduction of 2,4-Dihydroxyacetophenone
The Clemmensen Reduction in the Presence of a Solvent Miscible with Aqueous Hydrochloric Acid (Method II)
Preparation of 4-Chloro-7-methylindan
Reduction of γ-Keto-γ-(2-fluorene)-butyric Acid
The Clemmensen Reduction in the Presence of a Solvent Immiscible with the Hydrochloric Acid (Method III)
Reduction of β-Benzoylpropionic Acid
Reduction of β-(p-Anisoyl)-propionic Acid
Reduction of Stearophenone
The Clemmensen Reduction in the Presence of Solvents of Both Types (Method IV)
The Clemmensen Reduction with Unamalgamated Zinc (Method V)

The Hive - Clandestine Chemists Without Borders
(Chief Bee)
05-21-04 06:45
No 508584
      Organic Reactions: The Wolff-Kishner Reduction
(Rated as: excellent)

The Wolff-Kishner Reduction
David Todd
Organic Reactions, Volume 4, Chapter 8, pp. 378-4?? (1948) (../rhodium/pdf /or.wolff-kishner.pdf)


Scope And Limitations
Side Reactions and Abnormal Reductions
Variations in the Wolff-Kishner Method
Reduction at Atmospheric Pressure
Comparison with Other Methods
Table I. Comparison of Wolff-Kishner and Clemmensen Reductions
Experimental Procedures
Wolff Reduction of a Hydrazone
Reduction of Camphor
Reduction of 1-Keto-8-methyloctahydropyridocoline
The Direct Wolff Reduction
Reduction of 2,4-Dimethyl-3-acetyl-5-carbethoxypyrrole
Kishner Reduction of a Hydrazone
Reduction of Ethyl Cyclobutyl Ketone
Reduction of 4-Methylacetophenone
Kishner Reduction of a Semicarbazone
Reduction of cis-β-Bicyclooctanone
Wolff-Kishner Reduction without an Alkaline Catalyst
Reduction of 2,3-Benzo-1-azafluorenone
Reduction of Pyrene-3-aldehyde
Direct Wolff-Kishner Reduction at Atmospheric Pressure
Reduction of 5-Keto-8-methylnonanoic Acid
Reduction of β-(p-Phenoxybenzoyl)-propionic Acid

The Hive - Clandestine Chemists Without Borders
05-21-04 10:08
No 508622
      What are they doing?     

It looks like the reduction reduces the ketone to an alcohol, which then spontaneously dehydrates to an alkene in the acidic reaction conditions.

Very likely any kind of reduction that would produce an alcohol would have the same effect, due to the extra stability gained by conjugating with the benzene ring. Perhaps someone should try using the Meerwein-Ponndorf-Verley reduction, perhaps followed by strong H2SO4 or something to ensure full dehydration.

Or at least, that's how it plucks my wires.

Nice find.

We'll all meet someday...on the other side
(Chief Bee)
05-21-04 12:47
No 508645
      Simplicity is always nice     

Correct, reducing propiophenone to 1-phenyl-1-propanol followed by acid-catalyzed dehydration of the alcohol is a two-step route to the same alkene. The fancy thing about the ketone -> alkene reaction is that it proceeds in one step and consistently gives a good yield of the desired product.

The Hive - Clandestine Chemists Without Borders