Phenylpropanol Dehydration

[POPTART]

Swim has burrowed some 1-phenyl-3-propanol from the local grocery store. From what swim was able to find, psychokitty mentioned that dehydration of 1-phenyl-1-propanol is straight forward. but what about having the alcohol at the end of the chain. Swim wants to know if and how can the dehydration be done.
Dripping into hot sulfuric acid and having the propenylbenzene distill over?
Passing over some alumina?
Couldn't find much in the search.

Any ideas?

[Osmium]

Add a little bit of KHSO4 and distill. This should produce allylbenzene and some water, dunno if isomerisation to propenylbenzene will also take place. PIHKAL contains procedures for substituted 1-phenyl-1-OH-butanes, the same reaction conditions should work here.

[POPTART]

Thanks Osmium for the info. Here are a few more Q’s that SWIM has.

Lets say Swim has 200g of the alcohol, what would be a little bit of KHSO4?
Some extra information:
3-phenyl-1-propanol has a bp of 455 degrees
allylbenzene has a bp of 156=157 degrees
propenylbenzene has a bp of 172-172 degrees

Now refluxing this alcohol mean bringing the temp to 455 degrees (that is quite hot). Do you think Swim could do this under vacuum?
Overall, is Swim looking at a complete conversion?
Swim is also guessing that most of the product will the propenylbenzene, acid catalyzed dehydration right?

Where in PIKHAL is this mentioned (#), Swim is very interested in taking a look, but the file is so huge! Swim has already started to look…

Oh ya, is KHSO4 only found in chem stores (y or n). No sources!

[Rhodium]

To make your own KHSO4, mix 1 mole of KOH with 1 mole of H2SO4 (both diluted) and then evaporate the solution. There you have one mole of KHSO4 crystals.

As the bp of the alcohol is much higher than the bp of allyl/propenylbenzene, just distill off the alkenes as soon they are formed, as their boiling points are so low. As long as the alkenes are formed, the reaction temperature will not rise above the bp of the alkenes.

[Osmium]

The procedure must be somewhere in the J/Methyl-J/BDB/MDBD procedures.

I doubt that the alcohol has a boiling point of 455! Are you sure that´s not degree Fahrenheit? Assuming it is the BP would be around 235°C, which sounds much more reasonable.

[POPTART]

Osmium,
I believe that you are right, the BP is wrong. Will have to check that again. 235 degrees sounds more accurate. Actually, just checked the merck, it says 237-239 degrees (much better). thanks for pointing that out.

[Lino]

POPTART! 3-phenyl-1-propanol, b.p.=235ºc, F.W.=136.19, Phikal p698, also TS2 p239 for KHSO4 procedure (1g KHSO4/60g OH). SWIM found this bit v.tricky due to frothing of the alc./KHSO4 mix under vac. P-1-P-OH is far worse than toluene for this. The product requires much heat/vac. to climb up the still head, it then froths up and shoots down the condenser. Perhaps as Rhod. says, propenylbenzene wasn't formed, though some water certainly was.

SWIM's been considering PK's chem prof's lab notes. 1st dream failed to produce ketone. Unsure where the problem lay, could be L/T's mod. perf. or the dehydration. Producing 1-phenyl-1-propanol appears straight forward but Vogel's advice on this step is v.useful. Is it advantageous to add a little H2O to the MeOH, or anhydrous?

Regarding the dehydration. SWIM recommends you try this step in a MW oven…
In a 500ml Erlenmeyer flask, add 200-250g of your alc. and 3-4g KHSO4, then full power until it boils. Remove from MW and swirl, be careful of spitting oil. Return flask to oven and give it 2-3 min. longer, maybe on a lower power setting. There should now be steam and condensation visible, which shows the process is working (hopefully). Give it further cycles until no more water vapour appears. The sound it makes is like dropping frozen chips (french fries), into a hot deep fat fryer. When this noise ceases, after swirling and standing for a minute, it probably indicates the alc. is dehydrated. Give it one more cycle to make sure, your probable propenylbenzene should still be a clear pale yellow; perfect for further research as is. See L/T's latest performic.

Lino
Linoleum: the 13th element!  Now available at all good DIY stores… & Walmart.

[Lino]

Don't bother with the MW oven! SWIM thought longer about Rh's comments and re-read what Shulgin said. Then re-dehydrated the MW batch. Loads more fizzing, hissing and water: t'was clearly not done.

In a 500ml RB flask set up for distillation, 200ml P-1-P-OH was gently boiled following patient adjustment to the heat and strirring to ensure the vigorous frothing did not overshoot into the condenser. Vac. cannot be used at this stage and it takes 2-3 hours to dehydrate a batch. After such time  the fizzing and hissing subsides as H2O evolution ceases. You can then increase the temp. and stirring and a clear oil distills at 174º, (172/173º official) along with some water. When half the batch has distilled, let it cool and then apply vac. for the remainder. The oil comes over without too much frothing at 86º, 10mm hg.  Let us know how things go.
Linoleum: the 13th element!  Now available at all good DIY stores… & Walmart.

[PolytheneSam]

See this post

Post 178931 (missing)

(PolytheneSam: "PPA --> meth this easy?", Chemistry Discourse) Maybe the hydrogenation can be done at atmospheric pressure or another reduction method might work.
http://www.geocities.com/dritte123/PSPF.html

[Scooby_Doo]

Which one is it 1-Phenyl-3-propanol or 3-Phenyl-1-propanol (which has a bp of 235ºC not 455ºC).
To dehydrate just heat with the KHSO4 without vac until 170ºC then cool and distil under vac. This eliminates the bubbling and carry on.

Also J. Org. Chem. 1980 45, 917-919 uses anhydrous Copper (II) Sulfate to dehydrate 1-phenyl-1-propanol and 2-phenyl-2-propanol in 69 and 70% respectively.

[foxy2]

"Which one is it 1-Phenyl-3-propanol or 3-Phenyl-1-propanol"

Scooby they are both the same thing.


Do Your Part To Win The War

[terbium]

Scooby they are both the same thing.

Yes, I wasn't sure if he was asking that or just which of the two is the correct name. I would go with 1-phenyl-3-propanol as being the commonly used naming convention.

[Rhodium]

Lino: You did that dehydration of 1-Phenyl-1-propanol or 1-phenyl-3-propanol? The product was allylbenzene or propenylbenzene? What was the yield?

[foxy2]

Here is a Byzantine route, just to add a little spice to the thread.

Chugaev Method.





L. Chugaev (Tschugaeff), Ber. 32, 3332 (1899)
F. C. Whitman and C. T. Simpson, J. Am. Chem. Soc. 55, 3809 (1933)
P. G. Stevens and J. H. Richmond, J. Am. Chem. Soc. 63, 3132 (1941)
E. R. Alexander and A. Mudrak, J. Am. Chem. Soc. 72, 1810 (1950)
V. Franzen, Chem. Ztg. 79, 548(1955)
D. J. Cram, G. S. Hammond, Organic Chemistry (McGraw-Hill, New York, 1959), p 405
C. H. DePuy and R. W. King, Chem. Rev., 60, 444 (1960)
H. R. Nace, Organic Reactions, 12, 57 (1962).

from

http://www.geocities.com/chempen_software/reactions/RXN149.htm

Do Your Part To Win The War

[Rhodium]

I don't want to know what COS smells like, and I know that I will avoid smelling CH3SH the rest of my life after the first time I smelled it.

[obituary]

sulfur compounds just plain suck when it comes to smell

think skunk

[Lino]

Rhodium: SomeBee sez she de-hydrated P-1-P-OL from P-1-P following the NaBH4 treatment. The 'yields' at this point looked v.good. (she didn't weigh) Volume looked almost same c.200ml from 250g P-1-P.

Sadly: she ffff…sked up w/performic, probly over hydrolized or summat. The 100ml-ish oil contained c. 50ml of a viscous oil of high b.p. 20ml suspected prod. (smells nice) and 20ml poss. P-1-P-OL (same b.p. and smell). Further research is called for.

Errrrrrrr… this should have been propenylbenzene right? b.p. 175ish at atmospheric.
I just asked this in another post. How does the oxygen know which carbon to jump on during performic?
Linoleum: the 13th element!  Now available at all good DIY stores… & Walmart.

[foxy2]

Reduction of aldehydes and ketones.

Patent US4877909

Abstract
Aldehydes and ketones were reduced by treating with alcs. in the presence of zirconium oxide hydrate.  Thus, PhCOPh was refluxed with iso-PrOH in the presence of zirconium oxide hydrate obtained from ZrOCl2.8H2O to give 98% PhCHOHPh.

The catalytic reduction of aldehydes and ketones with 2-propanol over hydrous zirconium oxide.    
Shibagaki, Makoto; Takahashi, Kyoko; Matsushita, Hajime.
Bull. Chem. Soc. Jpn. (1988) 61(9), 3283-8. Journal in English.

Enantioselective addition of diethylzinc to benzaldehyde catalyzed by a small amount of chiral 2-amino-1-alcohols
Tetrahedron Letters, (1984) 25(26), 2823-2824
Nobuki Oguni, and Takao Omi

Procedure
To a stirred solution of benzaldehyde(9 mmol) and chiral 2-amino-1-alcohol(O.18 mmol) in toluene (15 ml) was added diethylzinc(9 mmol) under argon atmosphere, and the whole mixture was stirred at 20°C for 48 h. Then dilute HCl was added dropwise to the reaction mixture at 0°C and the organic layer was separated, dried over Na2S04, and concentrated under reduced pressure. The resulting 1-phenylpropan-l-ol was distilled under reduced pressure.
Results
-------------------------------------------------------------
Catalyst    Temperature(C)   Time(h)   Yield(%)
-------------------------------------------------------------
(S)-1-phenylethylamine   20   48   95
(S)-1-phenylpropan-1-ol   30   48   56
(S)-alaninol     20   41   97
(S)-valinol   20   44    95
(S)-leucinol   20   43   96
(S)-phenylalaninol   30  41   98
(S)-prolinol   30   42  100

Enantioselective addition of diethylzinc to benzaldehyde in the presence of ephedrine derivatives.
Chaloner, Penny A.; Perera, S. A. Renuka.
Tetrahedron Lett.  (1987),  28(26),  3013-14.
Abstract
Et2Zn adds to RC6H4CHO (R = H, m- and p-Me and -CF3, p-Br, m-Cl) in the presence of ephedrine and its N-alkyl derivs., to give 40-72% RC6H4CHEtOH in 52-80% enantiomeric excess at room temp. without special precautions. 

This is similar to the above article except they don't give exact details of the reaction.  The chiral catalyst is ephedrine, yeild 60%.  With N-isopropylephedrine the yeild is 72%.

Enantioselective reaction of diethylzinc with arenecarboxaldehydes in the presence of ephedrine derivatives.    
Chaloner, Penny A.; Langadianou, Eugenia; Perera, S. A. Renuka.
J. Chem. Soc., Perkin Trans. 1  (1991) (11), 2731-5.     
Abstract
The stereoselective alkylation by diethylzinc of aryl aldehydes was catalyzed by N-alkylephedrines to give 1-aryl-1-propanols.  The (1R,2S)-N-isopropylephedrine-catalyzed alkylation of 4-methylbenzaldehyde with diethylzinc gave (R)-1-(4-methylphenyl)-1-propanol in 73% yield in 73.7% enantiomeric excess.  The (1R,2S)-norephedrine-catalyzed alkylation of benzaldehyde with diethylzinc gave (R)-a-ethylbenzenemethanol in 99% yield in 55.8% enantiomeric excess.  The reaction mechanism was discussed. 


Using the procedure in

Post 292212

(foxy2: "1-phenyl-2-propanol synthesis", Novel Discourse)
First Grignard - PhMgBr
Second Grignard - EtMgCl
Yeild 1-phenyl-2-propanol = 84%

Methylation-hydroxylation of certain aromatic unsaturated compounds.

Patent US3806548

Synth from styrene, peracetic acid and UV light.
Full Text:

Post 481881

(Aurelius: "US pat 3806548  1-phenyl-1-propanol from styrene", Chemistry Discourse)

Preparation of 1-phenylpropanol as choleretic agent.
Oda, Shingo; Aoyama, Hiroshi.
Jpn. Kokai Tokkyo Koho  (1987), JP 62169739  A2  19870725  Patent In Japanese.
Abstract
EtCH(OH)Ph (I), useful as chloretic agent (no data), is simultaneously prepd. with styrene oxide (II).  A 10% soln. of Fe(NO3)3 in HOAc was added to 0.5 mol styrene at 55°, followed by 1.0 mol 30% MeCO2OH, and the mixt. kept 10 min at 55° to give I 22.6, II 53.1, and PhCH2CHO 0.3%, vs. 30.1, 28.0, and 12.3%, resp., at 85°.


Reduction of aldehydes and ketones using sodium formate in 1-methyl-2-pyrrolidinone.    
J. Org. Chem.  (1981),  46(16),  3367-9.
Abstract
Several representative aldehydes and ketones were reduced to the corresponding alcs. using HCO2Na in refluxing 1-methyl-2-pyrrolidinone contg. potassium phosphate monobasic as a buffer.  A competitive expt. involving 4-MeC6H4CHO and MeCOCH2CH2Ph was conducted to show that reaction conditions could be developed for chemoselective redn. of aldehydes. 

Reduction of aldehydes and ketones to alcohols with hydrous zirconium oxide and 2-propanol.
Matsushita, Hajime; Ishiguro, Shigeo; Ichinose, Hiroshi; Izumi, Akira; Mizusaki, Shigenobu.   
Chem. Lett. (1985), (6), 731-4. 
Abstract
RCHO (R = EtCHMe, pentyl, nonyl, Ph, 4-Me2CHC6H4CH2CHMe, Pr, Me2CH), R1COR2 [R1 = Ph, octyl, heptyl, Et; R2 = Me, Et, Ph; R1R2 = (CH2)5, CH2CH2CHMe, CH:CHCOCH:CH] and camphor were efficiently reduced with Me2CHOH in the presence of Zr(OH)2O.  RCHOH and R1R2CHOH were easily isolated in the pure state by filtering off the Zr(OH)2O followed by solvent evapn.

Reduction with Raney nickel in aqueous sulfuric acid.
Okimoto, Mitsuhiro; Chiba, Toshiro; Takata, Yoshiyuki.
Nippon Kagaku Kaishi (1985), (9), 1671-5.
ISSN: 0369-4577.  Journal in Japanese.  CAN 105:42295
Abstract
Lab. scale redn. was achieved by adding sulfuric acid to the mixt. of substrate and Ra/Ni either in aq. soln. or aq. methanol soln. at room temp.  Ketones and aldehydes were reduced to the corresponding alc. in good yields.  By use of an excess Ra/Ni, the redn. of ketones contg. a carbonyl group directly attached to an arom. nucleus gave the corresponding hydrocarbons.  Olefinic double bonds were likewise readily hydrogenated under the same conditions.  The selective hydrogenation of unsatd. ketones to the satd. ketones was possible with adjustment of the amt. of Ra/Ni used. 

A new type of complex reagent, tetraalkyllead-titanium tetrachloride.    
Yamamoto, Yoshinori; Yamada, Junichi; Asano, Tetsuya.
Tetrahedron  (1992),  48(27),  5587-96.

A new type of stable, storable, and selective alkylating reagent, tetraalkyllead.
Yamamoto, Yoshinori; Yamada, Junichi.
J. Am. Chem. Soc.  (1987),  109(14),  4395-6. 
Abstract
Tetraalkylleads (R4Pb) reacted quite smoothly with aldehydes R1CHO in the presence of Lewis acids such as TiCl4 and BF3 to produce RR1CHOH in high to good yields.  For example, Et4Pb and Bu4Pb reacted with BzH, cyclohexanecarboxaldehyde, and octanal in the presence of TiCl4.  Even tetracyclohexyllead gave the alkylation product.  The reagent system, R4Pb/TiCl4, exhibited high chemoselectivity; only aldehydes underwent the alkylation in the presence of ketones.  Further, the new reagent exhibited high 1,2- and 1,3-asym. induction.  2-Phenylpropanal produced the Cram isomer in a ratio of 93:7 upon treatment with Et4Pb/TiCl4.  3-(Benzyloxy)butanal gave the chelation product in a ratio of 91:9 upon treatment with Bu4Pb/TiCl4. 

Alkylation of carbonyl compounds with alkylleads.

Patent JP63215644

Abstract
Carbonyl compds. are alkylated with alkylleads in the presence of Lewis acids.  The alkylleads may be R4Pb (R = C1-10 alkyl, C5-12 cycloalkyl).  A CH2Cl2 soln. of TiCl4 and a CH2Cl2 soln. of Et4Pb were successively added to PhCHO in CH2Cl2 at -78° and the reaction mixt. was gradually heated to -30° to give 96% PhCH(Et)OH.


A new convenient reduction of aralkyl ketones to alcohols using Raney nickel-ammonium formate.   
Chen, Fener; Zhang, Heng; Yuan, Wei; Zhang, Wenwen. 
Synth. Commun.  (1991),  21(1),  107-9.
Abstract
Redn. of RCOR1 (R = Ph, substituted Ph; R1 = Me, Et) with Raney Ni and ammonium formate in MeOH at room temp. gave 90-92% RCH(OH)R1. 

Catalytic hydrogen transfer over magnesia. XIII. Liquid phase reduction of substituted 1-phenyl-1-alkanones by 2-octanol.    
Glinski, M.   
Polish Journal of Chemistry  (2000),  74(,  1207-1209.  ISSN: 0137-5083.  Journal in English.   CAN 133:281301
Abstract
1-Phenyl-1-alkanones were reduced by 2-octanol in the liq. phase in presence of MgO as a catalyst to 1-phenyl-1-alkanols.  

Catalytic hydrogen transfer over magnesia. XII. Reduction of metameric 1-phenyl-X-butanones (X = 1, 2 or 3) by 2-propanol.  
Glinski, M.; Radomski, P.   
Pol. J. Chem.  (1999),  73(7),  1233-1235.
Abstract
Hydrogen transfer from 2-propanol to 1-phenyl-1-butanone, 1-phenyl-2-butanone, or 2-phenyl-2-butanone in the presence of magnesium oxide (MgO) catalyst gave the corresponding alcs., i.e., 1-phenyl-2-butanol, 1-phenyl-2-butanol and 4-phenyl-2-butanol, resp. 

Diisopropoxyaluminum trifluoroacetate. A new off-the-shelf metal alkoxide-type reducing agent for reduction of aldehydes and ketones. 
Akamanchi, K. G.; Varalakshmy, N. R.; Chaudari, B. A. 
Synlett  (1997),   (4),  371-372.
Those who give up essential liberties for temporary safety deserve neither liberty nor safety

[POPTART]

SWIM was told that the dehydration does not work. Unless swim missed something. Here is what the beetle heard.
Test 1:
124g of 3-phenyl-1-propanol
2g KHSO4

Clear liquid heated until reached 155 degrees where color changed to a clear dark yellow. At 174 degrees, boiling started and water was collected. At this temperature the solution had changed to a dark red-brown color. Roughly 8 mls or H2O collected with about 2 mls of yellow liquid. Continued to heat, but nothing. Color at end was dark brown-black solution. 5.5 hours from time of last water collected.

Test 2

123g alcohol
2g KHSO4
0.5 Hydroquinone

Solution is a clear yellow color. At 135 degrees orange-yellow color.170 degrees a solution is dark brown in color and strong bubbling was observed. Roughly 10 mls of H2O collected, no oil. Time 5 hours from 0-170 until boiling stops

Test 3:
The beetle is running low on alcohol   , so decides on microwork
5ml alcohol
3 drops of concentrated H2SO4
Heated and boiling starts at 170 until roughly 1ml of H2O is distilled, then temperature starts to rise to 220 where it was stopped. Color of solution at end was black. Reaction time roughly 1 hour from 0-170 when boiling stopped.

Well the water is removed, but the final product does not seem to be the alkene, at least not the one she is dreaming of.
Two more tries are possible with the limited amount of alcohol left. What can be done? Any help would be welcome.

What are the possibilities of adding diluted H2SO4 and boiling in order to shift the alcohol to the 2 or 1st carbon. Maybe then the dehydration would be easier.

later

[POPTART]

OK, SWIM heard that the product was not alkene but an ether. SWIM will try desolving the alcohol in toluene and repeating the dehydration.

[Osmium]

How do you know it didn't work? Distill your products!
I'm not fat just horizontally disproportionate.

[Ritter]

Poptart,

The easiest, sure-fire method of dehydrating either 3-phenyl-1-propanol or 3-phenyl-3-propanol is to dehydrate it with some tosic acid in refluxing toluene.  A Dean-Stark trap should be placed between the still pot and the reflux condensor to monitor the progress of the reaction and keep the equilibrium shifted to the right.  The progress of the reaction can be monitored by keeping an eye on the amount of water collecting in the trap.  This is a very clean reaction and produces very high yields of alkene when applied to 3,4 methylenedioxyphenyl-1-butanol.

[POPTART]

Sorry Osmium, SWIM tried distillation of products. Nothing at 160, nothing at 180 and nothing came out at 250 degrees (swim stopped at 260). Water is generated, but no alkene.

Thanks Ritter. What is the mechanism E2 or E1?

???The problem with this dehydration is the alchol attacking the carbon -C-OH2+ (swim believes this happens only with primary alcohols). if the alcohol solution would be diluted enough then this would be minimized??? input!