Sciencemadness Discussion Board

P2P via Tosic acid. Results.

FriendlyFinger - 13-4-2005 at 21:18

65g Trans Beta-Methylstyrene, 330g DCM and 8.3g Na2CO3 was placed in a 1L RBF and stirred. 137.3g 86% Formic acid and 82.9g 35% H2O2 was mixed, left for 1 hour then placed in the freezer till 0 deg.

The Performix was dropped in over 3 hrs keeping temp 39-40 deg. 22hrs later it was separated, washed with 100ml 10% NaHCO3 and Na2CO3 (by mistake) then 2x 100ml dH2O, dried, filtered and fractionally distilled. 9.4g Propenylbenzene and something else was recovered. Then at 133 - 137 deg @ approx 4mm was collected 59.3g of very clear viscous whatever the hell it is. 1,2-Phenylpropandiol? 12.3g was left in the reaction flask just because I didn't feel like finishing.

So! 30.1g of this glycol, 90ml toluene and 1.7g p-toluenesolphonic acid was placed in a 250ml RBF and set up with a dean stark trap and heated the oil bath to 140-150 deg C for 90 minutes. In that time 3.5ml water was collected.

Cooled, neutralized with 60ml 10% NaHCO3, washed with 60ml Brine and dried with MgSO4. Colour was golden honey. I felt good here! Filtered into a 250ml RBF and set up for simple distillation. Removed most of the toluene then transfered to a 100ml RBF and set up for vacuum fractional distillation with a packed claison adaptor. With bath at 120 deg @8mbar, no sign of P2P. No problem. So far was running as planned. 0.4g Tosic acid was added so with bath at 140 deg @9mbar came light yellow P2P. For a while, then stopped. Shit!! Not like before! 0.5 g extra was added and when vacuum was applied P2P came gushing over, for a while. Added another 0.4g and distilled to the end.

21.3g raw P2P was collected and 5.5g black residue.

I ran this same amount twice before with less problems and better yield. For instance, during the final distillation only about 0.4g was added and P2P came over nonstop till the end. I used both Toluene and Xylene with the same outcome.The only difference was how I got the Glycol.

The first two times I tried to run a full modified performic with the 15%H2SO4 @80 deg thing. Failed. The glycol residue from this was used for a very sucussful rearrangment with Tosic. I've run many other Performic nightmares and have never been successful at rearranging with H2SO4.

The thing I want to know is why don't I get a full load P2P when refluxing in toluene with 6%w/w tosic. There is some P2P formed but only a drop or two. I've even used twice that amount with the same results. I tried Xylene because I thought the reaction temp might be higher. I was actually more confident this time because I collected more water in the trap, 3.5ml as apposed to 2.7ml as in previous runs. So does anyone have a clue cause I frigging don't! I know there are other ways to P2P, but I want to conquere the Performic like the MDP2P guys.

Kind regards,
FF.

FriendlyFinger - 13-4-2005 at 22:17

Here’s what I did with the rest of the glycol.

42g Glycol with 1.8g Tosic acid and 90ml toluene was refluxed with a dean stark again.After 2 hours I realised the tosic and toluene values were wrong so I added an extra 0.7g tosic and 40ml toluene. After a total of 3 and ½ hrs, 3.4ml water was collected. Colour was much darker then before.

Neutralized, washed, dried, filtered, removed toluene with vacuum, transferred to smaller flask then fractionally distilled. With bath @128 deg C, @7.5mbar, P2P came over at 80 deg. About 10ml came over very very slowly, then there was a sudden loss of vacuum then regained slowly and P2P stopped. Added 0.5g tosic and P2P started coming over again until a higher fraction started coming. Stopped and added another 0.5g tosic and P2P started coming over again almost clear. Towards the end there was a dramatic loss of vacuum up to 25mbar which then started climbing back but that was the end of P2P. Bath was up to 176 deg. What was that? Did something blow up? The tosic? That’s what the flask looked like. The and a portion of the rashig rings

22.8g raw P2P was collected and 5.3g residue in reaction flask.

P2P via TsOH without solvent

FriendlyFinger - 25-4-2005 at 00:18

Anyway here's what I did next; P2P via TsOH without solvent.

25g glycol and 1.8g TsOH was placed in a 100mm RBF and set up for simple distillation in an oil bath. With bath at 130 deg C, aqueous stuff was seen creeping up into the head then at 140 (bath) started coming over. Took bath up to 155 deg. 15 minutes passed between seeing distillate and removing bath.

Transfered to a 250ml sep with 75ml DCM, neutralised with 50ml 10% NaHCO3, then brine and dried with MgSO4 and set up for simple fractional distillation in a water bath. After DCM was removed, transfered to a 100ml RBF. removed rest of DCM with vacuum and distilled very clear P2P.

Collected 15g P2P with 4.5g golden stuff as residue, which I'm willing to bet, can be rearranged in another run.

I'm exited by this reaction but I think it might be difficult to time it perfectly when scaling up, even so, it was quick and clean.

Kind regards,
FF.

PS, Does anyone have BP info on the glycol?

Boiling points

Kinetic - 25-4-2005 at 10:46

Nice work, thanks for sharing.
This should work on the more interesting propenylbenzenes too, which are easy to make from the corresponding propiophenone (most of which can be readily made by a Friedel-Crafts acylation on your arene of choice).

The only boiling points listed for the glycol are under reasonable vacuum, suggesting it may be unstable when heating to its atmospheric boiling point. Perhaps it will rearrange to the desired product spontaneously.;)
I was quite surprised to find the glycol is a solid, melting at either 52-53C or 92-93C, depending on whether it is a 'high-melting' or 'low-melting' form (probably the threo- or erythro- diastereoisomers).
The listed boiling points are:
Either 99C or 118C at 1 torr (the former looks more believable);
121-121.5C at 3 torr;
127-127.5C at 3.5 torr;
and 154-156C at 17 torr.

Organikum - 25-4-2005 at 12:36

Quote:

propenylbenzenes too, which are easy to make from the corresponding propiophenone
Will you tell me how? Just some keywords for the further search are enough.

thanks
/ORG

Kinetic - 25-4-2005 at 13:00

How to make propenylbenzenes from propiophenones? I thought you would know, especially as I linked a one-pot method in a thread of yours not too long ago.;)
You can do it in either one step or two. The two step method, of course, involves reduction of the carbonyl to an alcohol and subsequent dehydration, usually with KHSO4. See http://rhodium.moppy.net/www.rhodium.ws/chemistry/propioprop... and FriendlyFinger's work archived in http://rhodium.moppy.net/www.rhodium.ws/chemistry/p1pol.elim... for these steps. I can do a literature search if you want to see what alternatives are available to NaBH4.
Shulgin uses this dehydration in his synthesis of 3,4-methylenedioxyphenyl-2-butanone: http://www.erowid.org/library/books_online/pihkal/pihkal094....

The one-pot method is probably most suited to you since it's very OTC: http://rhodium.moppy.net/www.rhodium.ws/chemistry/arylketone...

Organikum - 25-4-2005 at 16:08

Thanks kinetic, you are right on this of course. But I have not been able to do or read much chemistry for months and I got a little bit bit rusty....
...hope this will change in about two month from now.

/ORG :(

Sandmeyer - 27-4-2005 at 05:53

benzylic ketones are reduced to alcohols in excellent yields with sodium dithionite.

Search engine fault?

UpNatom - 27-4-2005 at 14:25

Quote:

Just some keywords for the further search are enough.


That's interesting, I double checked my post because I was sure the keywords propiophenone and propenylbenzene are in it (they are) and should have brought you here, but lo and behold a big fat nuthin from the search engine.

What up with that?

Organikum - 27-4-2005 at 15:13

The search function of the board is poor - use Google instead:
xxxxxxx site: sciencemadness.org
this works well.

I already explained my main problem, thanks for the spooning.

/ORG

JohnWW - 27-4-2005 at 15:39

If the URL of a site desired to be searched specifically starts with "www.", this has to be included in the search parameter, i.e. site:www.sciencemadness.org

neutrino - 27-4-2005 at 16:33

No, just "site:sciencemadness.org" works.

Organikum - 27-4-2005 at 20:21

because nicely http://sciencemadness.org
as http://www.sciencemadness.org , both resolve to the same old board.

Wonders of algorythm! Praise!

UpNatom - 28-4-2005 at 11:12

Quote:

thanks for the spooning.


Eh?

Anyway..using google to search for those keywords yields one hit and it isn't the thread in question.

Organikum - 8-5-2005 at 12:23

Regarding Sandmeyers post:
Quote:

Subject: dithionite aldehyde/ketone reductions
Posted by: GC_MS (Hive Addict)
Posted on: 05-19-03 09:59
Post No: 434107

Sodium dithionite as a reductant for aldehydes and ketones
JG de Vries e.a. Synthesis (1977) 246-247

Sodium dithionite, Na2S2O4, is a reducing agent widely applied both in the laboratory and industry. It is commonly used in biochemistry for the reduction of a variety of coenzymes and enzymes and in organic chemistry to reduce several types of functional groups, especially those containing nitrogen. [...] General procedure for the reduction of aldehydes and ketones: a solution of substrate (50 mmol) in dioxan (175 mL) or DMF for more difficulty reducible substrates (cf table), is added to water (175 mL) containing sodium hydrogen carbonate (27.5 g). When no cosolvent is used, the substrate is added neat. Sodium diothionite (12.5 g) is added and the reaction mixture refluxed for 4 h during which time three additional 12.5 g portions of sodium dithionite are added. The reaction is carried out under an atmosphere of nitrogen. After cooling to rt, water is added until the solution becomes clear and thereafter the solution is extracted with ether (furfuryl alcohol and gamma-valeroacetone were isolated by continuous extraction with ether for 7 and 72 hours respectively). When DMF is used as cosolvent the ether extracts are back-washed twice with water to remove traces of DMF. After drying (MgSO4) and removal of the ether, the products are isolated by either distillation or recrystallization. Identification is based on boiling points, IR and 1H-NMR spectra, and comparison with authentic materials.

SUBSTRATE PRODUCT SOLVENT YIELD
Ph-CHO - Ph-CH2OH H2O/dioxan 84%
Ph-COCH3 - PhCHOHCH3 H2O/dioxan (1/1) 30%; H2O/DMF (1/1) 94%

Maybe they might be useful for certain propiophenones (as alternative to NaBH4)... Who knows


DMF is a hard to come by solvent. How are yields without co-solvent? Can ethanol be used as co-solvent?
Would a Al/Hg not be favorable in yields when no DMF is available?

/ORG

[Edited on 8-5-2005 by Organikum]

Organikum - 8-5-2005 at 12:47

European Journal of Organic Chemistry
Volume 2002, Issue 19 , Pages 3326 - 3335

Published Online: 20 Sep 2002
Quote:

Facile Reduction of Aromatic Aldehydes, Ketones, Diketones and Oxo Aldehydes to Alcohols by an Aqueous TiCl3/NH3 System: Selectivity and Scope Angelo Clerici, Nadia Pastori, Ombretta Porta * Dipartimento di Chimica, Materiali ed Ingegneria Chimica Giulio Natta del Politecnico, Sezione Chimica, Via Mancinelli 7, 20131 Milano, Italy *Correspondence to Ombretta Porta, Dipartimento di Chimica, Materiali ed Ingegneria Chimica Giulio Natta del Politecnico, Sezione Chimica, Via Mancinelli 7, 20131 Milano, Italy Keywords Aldehydes • Chemoselectivity • Ketones • Reduction • Titanium trichloride

Abstract
A simple and rapid procedure for the almost quantitative reduction of aromatic aldehydes, ketones, diketones and oxo aldehydes to alcohols by use of TiCl3/NH3 in aqueous methanol solution is reported. The reducing system distinguishes between different classes of aldehydes and/or ketones, and many functionalities that usually do not survive under reducing conditions are tolerated well. The concept of reversal of chemoselectivity has also been developed. A mechanism based on two sequential one-electron transfers from TiIII to the carbonyl carbon atom is proposed, the second SET becoming operative only in the presence of ammonium ion (either added or formed in situ).
(© Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002)
Received: 15 April 2002
Digital Object Identifier (DOI)
10.1002/1099-0690(200210)2002:19<3326::AID-EJOC3326>3.0.CO;2-V


Can somebody retrieve this article or link to it so it is already retrieved - I couldn´t find it.

Also I believe that Sn/SnCl2 should work - perhaps with NH3 - to redide the ketone.

regards
/ORG



[Edited on 8-5-2005 by Organikum]

Sandmeyer - 8-5-2005 at 13:18

Quote:
Originally posted by Organikum
Regarding Sandmeyers post:

DMF is a hard to come by solvent. How are yields without co-solvent? Can ethanol be used as co-solvent?
Would a Al/Hg not be favorable in yields when no DMF is available?

/ORG

[Edited on 8-5-2005 by Organikum]


Yes, but I'm sure will work with NMP (N-methyl pyrrolidine) equally well, if not even better, as it has the same characteristics DMF has and is in some applications even preferable over DMF. It is available OTC as a GBL substitute for the removal of grafitti.

Requested article from European Journal of Organic Chemistry

Mephisto - 8-5-2005 at 13:36

Quote:
Originally posted by Organikum
Can somebody retrieve this article or link to it so it is already retrieved - I couldn´t find it.
I've attached your document. ...Because it was always fun to exchange literature with you :)

~Mephisto

Attachment: European Journal of Organic Chemistry - Volume 2002, Issue 19 , Pages 3326 - 3335.pdf (206kB)
This file has been downloaded 3391 times

Kinetic - 8-5-2005 at 13:37

I can probably get that Eur. J. Org. Chem. article if nobody has provided it by tomorrow. [Edit: OK, I was beaten to it ;) ]

I did a search after my last post in this thread and came across a nice Meerwein-Ponndorf-Verley reduction which should be adaptable from the 4-methylthiopropiophenone the procedure is carried out on. It's pretty OTC, and the intermediate can be dehydrated using formic acid in unspecified yield.

Taken from J. Org. Chem., 17, 350-357 (1951):

4-(a-Hydroxypropyl)thioanisole (V) .
The starting 4-propionylthioanisole was obtained in 80% yield by a Friedel-Crafts reaction between 30 g. of thioanisole, 24 g. of propionyl chloride, and 40 g. of aluminum chloride in carbon disulfide (200 ml.). A mixture of 35 g. of this ketone, 50 g. of aluminum isopropoxide, and 200 ml. of anhydrous 2-propanol was gently refluxed with removal of acetone until the latter could no longer be detected in the distillate. After cooling, the reaction product was treated with cold dilute hydrochloric acid, and extracted with ether; the ether solution was washed with an aqueous solution of sodium carbonate, then with water, dried over sodium sulfate, the solvent removed and the residue vacuum-fractionated. Yield, 98% of a pale yellow, rather viscous oil, boiling at 160-162'/17 mm.


For the dehydration of the butyryl homolog:

The crude alcohol obtained was dehydrated by ten minutes' boiling with 4 times its weight of 98% formic acid; the resulting ethylene was taken up in benzene, and the benzene solution washed with an aqueous solution of sodium carbonate, then with water, and dried over sodium sulfate. After removal of the solvent, the residue gave on vacuum-distillation a fluid, colorless liquid, b.p. 153'/15 mm., with a less pronounced aniseed odor than the lower homolog.

[Edited on 8-5-2005 by Kinetic]

FriendlyFinger - 12-7-2005 at 21:14

Solventless rearrangment with TsOH.
Better yield, more detail.

28.7g Glycol and 2.1 Toluenesulphonic acid monohydrate was placed in a 250 ml RBF with a stir bar and set up for simple distillation in an oil bath without water in the condenser. Heat was applied and after a while a few droplets of water came over. Nothing else was expected. Max bath temp was 148 deg C.

When the oil bath was at 110 deg C, flask wall was frosty with water vapour and at 125 deg, water droplets were forming at the distillation head and at 130 deg, were running down into the flask. This took 24 minutes. Tempreture to 145 deg, time 40 minutes. Heat up to 148 deg. Total time from when water formed droplets till removal of bath was 50 min. Cooled to room temp with fan and water bath approx 10 - 15 min.

Added 90 ml DCM and neutralised with 90 ml 10% NaHCO3, washed with 40 ml brine. Colour at this point was golden like light beer. Dried with MgSO4, placed in a 250 ml RBF, removed DCM then vacuum fractionally distilled the suspected P2P which came over at 5.25 mbar at 75 deg all the way. Collected 18.1g with 4 g residue as a dark thick liquid, did not turn solid. Yield 71.5%. This has not been aminated yet, so god only knows if it's any good.

I don't think this is an ideal way to do it, because you can easily destroy the P2P if not timed well and I have doubts about scaling up, but any comments would be appreciated.

Regards,
FF