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Author: Subject: Propiophenone rearrangement

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[*] posted on 5-3-2005 at 14:01
Journal requested

Anyone have: 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) ?

A rather elegant method (if not quite so elegant as a straight up rearrangement) describes the reduction of propiophenone to propenylbenzene using Zn amalgam in EtOH and formic acid mixture, which can then of course be oxidised to p2p. Yields are high for both steps.
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[*] posted on 5-3-2005 at 15:14

This is a neat article, although I am a little put off by the use of mercury. I remember this was originally posted at the Hive by Regis, and it was archived by Rhodium. The best version of Rhodium's archive is surely that provided by mophead; thanks to him for providing the following: A Modified Clemmensen Reduction Procedure for the Conversion of Aryl Ketones into Aryl Alkenes.

I said earlier in the thread that I was working on a route to transform propiophenones to phenylacetones. I now know that the route is indeed successful and practical, at least when 1-(5-indanyl)-1-propanone is the starting material. The epoxide is made in about 80% yield from the propiophenone (bromine, then NaBH4 followed by KOH), and this is rearranged to the phenylacetone with 10mol% LiI in ethyl acetate in 63% yield. The low yield for the rearrangement was due to problems (severe bumping) with the distillation, leading to the loss of a significant amount of product. An NMR of the product obtained after redistillation was entirely consistent with the predicted spectrum for 1-(5-indanyl)-2-propanone.
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Hazard to Self

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[*] posted on 21-3-2005 at 17:45
P1P to P2P

I've tried this route;

P1P -- P1POH -- B-Methylsytrene, in high yield. Then Standard and modified performic to P2P in low yield with many problems.

After the initial performic, (modified) the H2SO4 rearrangement yielded zip. The stuff I (lots of loss) was rearranged sucessfully with Tosic acid. The yield was about 88%.

Has anybody sucessfully turned B-Methylstyrene in to P2P via Performic. Id like to meet you!

Kind regards FF
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International Hazard

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[*] posted on 8-8-2005 at 06:35

Someone in this thread suggested use of aluminium isopropoxide in reduction of alpha-bromo ketone IIRC. Following old Meerwein-Ponndorf-Verley reference gives mixture of products in low yield, so trying alternative reducing agent for this purpose is better, but that's another saga. Aromatic a-halo ketones could give slightly better yields.

The Reduction of -Bromocyclohexanone with Aluminum Isopropoxide
S. Winstein;
J. Am. Chem. Soc.; 1939; 61(6); 1610-1610

78.8 g. (0.428 mole) of bromocyclohexanone, b. p. 69-71 O (1.5 mm.;, prepared by the method of Kötz (Ann., 868, 196 (1907)) dissolved in 200 ml. of anhydrous isopropanol (Shell) was added to aluminum isopropoxide solution prepared from 7.5 g. of aluminum and 75 ml. of anhydrous isopropanol, according to the directions of Young, Hartung and Crossley (JACS 58, 100 (1936)). The mixture was refluxed for three and one-half hours. Then it was concentrated to a thick residue by distillation first of acetone, then of solvent through a 20- cm. column of glass helices for two hours at atmospheric pressure and finally with the aid of an aspirator. One hundred ml. of water and 130 ml. of 6 N sulfuric acid were added to the residue and all lumps were broken up. A little ether was added and the oil phase was separated, washed with bicarbonate solution and dried over sodium sulfate. Distillation and then refractionation at reduced pressure through a 40-cm. Weston column yielded 22.6 g. (30%) of 2-bromocyclohexanol, b. p. (10 mm.) 85.5-86.5 C, and 14.3 g. (33%) of cyclohexanol, b. p. (10 mm.) 61.0-61.2 C.


No doubt there are some oldschool chemistry fanatics at sciencemadness possibly interested in aluminium isopropoxide. I have bunch of unsorted references (not retrived papers) of its applications, in case someone is interested I can post. An interesting, and likely less known aspect of this wonderful reaction is that it is an equilibrium process - meaning that the reverse reaction (oxidation) can also be exploited. Pioneering chemist in this area was Oppenauer, he did a lot of work on steroids. He has oxidized steroids containing secondary alcohol groups in high yield (without harsh conditions) using acetone in benzene as the oxidation agent. Catalysts used were aluminum ter-butoxide as well as ordinary aluminium isopropoxide. When benzophenone, cyclohexanone, and quinones are used as oxizing agents the Oppenauer oxidations are extended to conversion of primary alcohols into their corresponding aldehydes. Advantage here over alternative methods for oxidation of primary alcohols to aldehydes is that overoxidation to carboxylic acid is fully avoided. It is shame that Meerwein-Ponndorf-Verley and especially Oppenauer has recived so little attention in litterature.

If someone can get these papers it would be cool:

Dehydration of secondary alcohols to ketones.I. Preparation of sterol ketones and sex hormones. Red. Trav. Chim. Pays-Bas, 56, 137, 1937. (Oppenauer)

This is supposed to be a review of the literature on Oppenauer oxidations up to date of publication:

Lehman, H., Houben-Weyl, 4th ed., Vol. 4/1 b; Muller, E., Ed.; Thieme: Stuttgart,
1975, p. 901.


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[*] posted on 8-8-2005 at 10:57

I agree, the trouble with the Meerwein-Ponndorf-Verley reduction for the reduction of alpha-haloketones is that there is a tendancy to reduce the halogen atom, leaving either the ketone or simply the alcohol, instead of the desired halohydrin. I would go so far as to say that this reduction system is unsuitable for this type of substrate, due to the side reactions and low yields. That said, there is an interesting article on the reduction of alpha-bromopropiophenone and the use of the resulting bromohydrin (obtained in low yield) in the preparation of ephedrine. The reduction step is below, taken from J. Am. Chem. Soc., 62, 1424-1428 (1938):

Reduction of alpha-Bromopropiophenone. -126 grams of the bromoketone, b. p. 127-129.5' (10 mm.), was added to a solution of 33.0 g of aluminum as isopropylate in 1200 cc. of isopropyl alcohol, and the solution boiled under a reflux distilling column for nine hours. The acetone was removed by fractional distillation. The combined distillate on treatment with alcoholic silver nitrate gave a precipitate of silver bromide equivalent to approximately 8% of the total bromine, indicating the presence of isopropyl bromide. Propylene was also present as evidenced by rapid reduction by aqueous permanganate. Most of the isopropyl alcohol was removed in vacuo, and the residual paste mass poured onto ice and dilute sulfuric acid, extracted with ether, washed with dilute acid, water, potassium carbonate, sodium hydroxide, water, dried over anhydrous potassium carbonate and distilled: first fraction up to 75' (0.1 mm.), second fraction, 44 g., b. p. 75-95' (0.1 mm.). The black tarry residue weighed 42.7 g. Redistillation of the second fraction yielded the bromohydrin, a somewhat viscous yellow-brown oil, b. p. 73-75' (0.1 mm.), n25D 1.5611.

If phenylacetones are the desired product and you really have an urge to use this reduction, it would be far better to reduce the propiophenone itself, then dehydrate it and oxidise to the phenyl-2-propanone. The reduction works beautifully on propiophenones; I posted a synthesis from an article towards the bottom of this thread: P2P via Tosic acid. Results.

I should have access to the Recl. Trav. Chim. Pays-Bas paper requested by Sandmeyer. Unfortunately I won't be able to get it any time soon, but I will add it to my ever-increasing list of 'Wanted References'.
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[*] posted on 8-8-2005 at 15:46

Here's that Oppenauer paper request by Sandmeyer. Somebody else will have to translate it and I couldn't find a electronic copy so the file is a scan.

[Edited on 8-8-2005 by epck]
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[*] posted on 20-2-2012 at 01:55

Quote: Originally posted by Organikum  

Original reference is:
J. Pharm. Soc. Japan 73,1224-6 (1953)


The reference trail proceeds through the J.Pharm.Soc.(Japan) to give

Ichiro Hirao, "Acetylenic Alcohol and its Derivatives. IV Synthesis of Propiophenone and 3, 4-Methylenedioxypropiophenone"
Yakugaku Zasshi, Vol.73(11) 1953 pp.1224-6 (Abstract)

There has to be a better route from propiophenone to the dione though, surely? Despite that, if the experimental details become available (from the Japanese language article) showing how to condense acetylene with benzaldehyde/piperonal to give the P-1-P-ol/P-1-P in good yield, I'm sure many will be interested - I do recall another article - maybe the same journal (for sure the same Country & period) which details a very similar reaction schema (with acetylides as an intermediate IIRC). There is also this one by the same author (same journal), very similar reagents:

Ichiro Harao, "Studies on Phenylethynyl Carbinol and Its Derivatives. I Synthesis of 3, 4-Methylenedioxyephedrine" Yakugaku Zasshi, Vol.72(8) 1952 pp.1006-9 (Abstract)

[Edited on 20-2-2012 by aliced25]

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