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[*] posted on 28-5-2019 at 03:46
Pathways to phenethyl alcohol


Folks,

I’m planning to give a go at synthesising phenethyl alcohol, to use as a perfume component.

Knowing that I can start from benzene, toluene or benzyl alcohol, I thought that I could:

1. Make iodobenzene, then phenylmagnesium iodide then a Grignard reaction with 2-chloroethanol. 2-chloroethanol apparently can be made by bubbling ethylene (from alcool + sulphuric acid over 160 °C) in bleach.

2. Make benzyl chloride (benzyl iodide?), then benzylmagnesium chloride/iodide and another Grignard reaction with formaldehyde
(I have a 40% solution of formaldehyde).

Benzyl chloride I can derive from toluene, or maybe better from benzyl alcohol and hydrochloric acid.

Which way would be the more practical? Also is there another, easier way to go?
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[*] posted on 28-5-2019 at 03:54


"Perfume component", sure.
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[*] posted on 28-5-2019 at 04:15


Quote: Originally posted by DavidJR  
"Perfume component", sure.


Doesn't it smell like roses?

[Edited on 28-5-2019 by Keras]
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Pumukli
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[*] posted on 28-5-2019 at 04:34


2-chloro-ethanol in a Grignard reaction? Think it over. :) (OH)

Grignard reaction with formaldehyde solution? It contains water! Grignards does not like water!
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[*] posted on 28-5-2019 at 04:47


Quote: Originally posted by Pumukli  
2-chloro-ethanol in a Grignard reaction? Think it over. :) (OH)


So Ph-MgCl + Cl-R-OH doesn’t lead to Ph-R-OH + MgCl2? Oh, yeah, Cl-R-O-MgCl. Not really useful. Bad idea, you’re right.

Quote: Originally posted by Pumukli  
Grignard reaction with formaldehyde solution? It contains water! Grignards does not like water!


Yeah, I know. I'd have to make the solution boil and use gaseous formaldehyde. TBH, that’s why I asked here: I know there are catches.

[Edited on 28-5-2019 by Keras]
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[*] posted on 28-5-2019 at 04:51


Do a grignard with halobenzene on ethylene oxide to get phenethyl alcohol in one step. Should be fairly straight forward I think.
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[*] posted on 28-5-2019 at 04:57


(OH) was a hint.
The OH group is not tolerated in a Grignard reaction. That H is too acidic and decomposes the reagent. It will form R-H (and MgOHCl or other magnesium salt.)

The problem may be worked around by using 2 equivalents of Grignard reagent. First one is wasted and yields benzene, the second one may react via the expected way.

Boiling the formaldehyde solution is not enough: you need dry formaldehyde. Paraformaldehyde is the usual reagent in such reactions, because it is a dry powder and on heating it decomposes to formaldehyde gas.

On paper (or screen) the ethylene-oxide reaction looks nice. In a real amateur laboratory - or in the hands of a less experienced fellow, it can be disastrous. Ethylene-oxide is a gas, which is poisonous, carcinogene and on top of that explosive too.



[Edited on 28-5-2019 by Pumukli]
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[*] posted on 28-5-2019 at 04:58


Quote: Originally posted by laserlisa  
Do a grignard with halobenzene on ethylene oxide to get phenethyl alcohol in one step. Should be fairly straight forward I think.


And ethylene oxide I could produce by dehydrating 2-chloroethanol with NaOH or KOH, right?

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[*] posted on 28-5-2019 at 05:25


Quote: Originally posted by Pumukli  
(OH) was a hint.
On paper (or screen) the ethylene-oxide reaction looks nice. In a real amateur laboratory - or in the hands of a less experienced fellow, it can be disastrous. Ethylene-oxide is a gas, which is poisonous, carcinogene and on top of that explosive too.
[Edited on 28-5-2019 by Pumukli]


Yeah, that’s why I didn't mention this route at first. But ethylene oxide is liquid under 10 °C, so working in an ice bath + salt could maybe solve the problem?


[Edited on 28-5-2019 by Keras]
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[*] posted on 28-5-2019 at 06:04


It may solve the problem. I suggest though to look up some real preparation with ethyleneoxide before volunteering into such a synthesis based on the info in this thread!
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[*] posted on 28-5-2019 at 06:24


Quote: Originally posted by Pumukli  
It may solve the problem. I suggest though to look up some real preparation with ethyleneoxide before volunteering into such a synthesis based on the info in this thread!


Yup. Good idea. Also, paraformaldehyde apparently can be made by evaporating a formaldehyde solution with a bit of sulphuric acid?
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[*] posted on 28-5-2019 at 07:41


Quote: Originally posted by Keras  
Make benzyl chloride (benzyl iodide?), then benzylmagnesium chloride/iodide and another Grignard reaction with formaldehyde
(I have a 40% solution of formaldehyde).
This route won't give the expected product - https://www.thevespiary.org/rhodium/Rhodium/pdf/bzmgcl.abnor...

The easiest way IMO would be hydroboration oxidation of styrene.If that's not possible,then an anti markonikoff hydrobromination,followed by an Sn2 hydration should give the target compound -http://www.sciencemadness.org/talk/viewthread.php?tid=61976#...
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[*] posted on 28-5-2019 at 11:39


Quote: Originally posted by CuReUS  

This route won't give the expected product - https://www.thevespiary.org/rhodium/Rhodium/pdf/bzmgcl.abnor...

The easiest way IMO would be hydroboration oxidation of styrene.If that's not possible,then an anti markonikoff hydrobromination,followed by an Sn2 hydration should give the target compound -http://www.sciencemadness.org/talk/viewthread.php?tid=61976#...


Thanks, I wasn't aware of this. It's always a good idea to discuss reactions here before even attempting them.

Your route entails I have styrene available, which I have not. Besides, I have no idea how expensive is BH3 in THF. HBr anti-Markovnikov could be a possibility, but that still poses the styrene availability problem.

Finally, the oxirane route seems the most practical, despite having to be done in an ice bath using 2-chloroethanol.
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[*] posted on 28-5-2019 at 12:56


Lets see what what P. Z. Bedoukian says about this in Perfume and Flavoring Synthetics

1: Reduction of phenylacetaldehyde with sodium amalgam in aqueous alcohol (Radziszewski, Ber., 9 (1876) 373.)

2: Reduction of phenylacetaldehyde by hydrogen with nickel or palladium catalysts (Skita and Rojahn, Ber., 33 (1900) 1723)

3: Phenyl acetic acid reduction by Bouveault-Blanc reduction (sodium in absolute alcohol). (Bouveault and Blanc, compt Rend, 137 (1903) 61.)

4: Phenyl acetic acid reduction by sodium aluminum hydride in THF. (Pitha, Hermanek and Vit (Collection Czech Chem. Commun.,25 (1960) 736; C. A., 54 (1960) 13055.

5: alkaline borohydride reduction of esters (Paul and Joseph, Bull. Soc. Chim. France, (1952) 550

6:Ethyl phenyl acetate in liquid ammonia using sodamide (Chabley, Compt. Rend. 156 (1913) 1022.

7: Electrolytic reduction of phenylacetic acid in 75% sulfuric acid with a lead cathode gives phely ethyl phenylacetate which can be saponified to give phenylethyl alcohol. (Marie, Marquis and Birkenstock, (Bull. Soc. Chim. France, [4], 24 (1919) 513.

8: Styrene plus Hydrogen chloride to give phenyl ethyl chloride, which on hydrolysis with weak aqueous alkalis gives phenylethyl alcohol. (Britton, Coleman and Hadler, US patent 2,185,141 Dec. 26, 1939 )

He warns against diphenyl as a difficult to remove and smelly impurity in most Grignard processes for making it, but says these Grignard reaction paths have been used commercially. (the smell would be important to your perfumery plans, but probably less so to people with more stimulating aims in mind)

Apparently a lot of work has gone into using chlorobenzene instead of the bromo or Iodo benzenes as an economic measure. (forcing under pressure, special magnesium alloys, treating the magnesium turnings with hallides of copper, aluminum or silver, etc)

He lists others, but most involve ethylene oxide.
Besides, I'm tired of copying stuff.

Edit: putting the word phenyl too close to a colon made it look like I was sticking my tongue out at you. No offense, just poor text spacing.
.




[Edited on 28-5-2019 by SWIM]





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[*] posted on 28-5-2019 at 19:53


Quote: Originally posted by Keras  
Your route entails I have styrene available, which I have not
Then go to your nearest hardware store and get it.Its sold OTC as paint thinner ;)
Quote: Originally posted by Keras  
Besides, I have no idea how expensive is BH3 in THF
There is something called "google"... :P
Quote: Originally posted by SWIM  
Styrene plus Hydrogen chloride to give phenyl ethyl chloride, which on hydrolysis with weak aqueous alkalis gives phenylethyl alcohol.
Interesting.I thought HCl couldn't undergo anti-markonikoff reaction :o

EDIT : SWIM ,I understood how that reaction happens.HCl isn't undergoing an antimarkonikoff,its just reacting normally with styrene to give a mixture of 1 and 2-phenyl chloride.Even if they get 1% yield of the 2-phenylchloride,they can still make a lot of 2-phenylethanol since they run the reaction in tonnes as its an industrial method.

[Edited on 29-5-2019 by CuReUS]
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[*] posted on 28-5-2019 at 20:18


I just copied that stuff from the book mentioned.
Now I tried googling the patent and it's listed but when I clicked on it it isn't coming up.
Hope I didn't post a mis-print.

Damn, it is a patent for making phenylethyl alcohol from beta halo ethylbenzenes, but says nothing about making beat halo ethylbenzenes.

Exact wording of description in book: Under controlled conditions, it adds hydrogen chloride to yield phenyl ethyl chloride...

But bedoukian doesn't describe those 'controlled conditions"
The other references for this is Salnikov and Volkov, Zhur. Priklad. Khim. 33 (1960) 2118
And C.A. 55 (1961) 3501

But for all I know they're just the hydrolysis reaction like the first reference.

Edit: oh well, read your explanation. Not exactly a lab worthy method then.






[Edited on 29-5-2019 by SWIM]

[Edited on 29-5-2019 by SWIM]

[Edited on 29-5-2019

Ozonolysis of allylbenzene with a reductive workup? (wild stab in the dark)

[Edited on 29-5-2019 by SWIM]





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[*] posted on 28-5-2019 at 23:50


Quote: Originally posted by CuReUS  
Quote: Originally posted by Keras  
Your route entails I have styrene available, which I have not
Then go to your nearest hardware store and get it.Its sold OTC as paint thinner ;)

I checked that out and most of the paint thinners I could get info on were made of xylene, toluene, ethylbenezene or a mix of those plus various ketones. No styrene, definitely.

Quote: Originally posted by CuReUS  

Quote: Originally posted by Keras  
Besides, I have no idea how expensive is BH3 in THF
There is something called "google"... :P


Yeah, right. Google's your friend. :p Ok, it's not cheap but not as expensive I was figuring.

Apparently, the ethylene oxide route is the easiest, since most of the routes SWIM quotes entails already having a compound that looks like phenethyl alcohol. No real synthetic way besides ethylene oxide.

[Edited on 29-5-2019 by Keras]
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[*] posted on 29-5-2019 at 00:18


Or, you could just extract the stuff from a commercial product, like hand lotion or fabric softener.

Of course, if you have a legit cosmetics business, you can just order it.

[Edited on 5/29/19 by PirateDocBrown]




Phlogiston manufacturer/supplier.

For all your phlogiston needs.
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[*] posted on 29-5-2019 at 02:50


Quote: Originally posted by PirateDocBrown  
Or, you could just extract the stuff from a commercial product, like hand lotion or fabric softener.

Of course, if you have a legit cosmetics business, you can just order it.

[Edited on 5/29/19 by PirateDocBrown]


Sure, but that’s cheating :)
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[*] posted on 29-5-2019 at 03:51


Whoa, SWIM, you weren't lazy! Came up with so many suggestions. I'd join the train of thoughts and suggest other routes to target compound. Preferably less dangerous, more OTC ones. :-)

So what if you started from OTC phenylalanine?
One theoretical route: phenylalanine -> 2-phenethylamine -> diazotisation with HNO2, N2 released, remaining cation takes up OH from water solution.
I know, yield would suffer from rearrangement to secondary corbocation and yield 1-phenethylalcohol along target compound. Purification may be possible via either distillation or making esters and distilling those esters.

There may be another possibility from phenylalanine:
decarboxylation to phenethylamine -> heating 2-phenethylamine in diethyleneglycol with KOH. This is a neat direct conversion of primary aliphatic amino groups to primary OH-s. Literature in attachement.
Diethyleneglycol may be substituted with brake fluid. Boiling point of 2-phenethylamine may be a problem. (Too low!)
In this case, or if you are concerned about isolating the 2-phenethylamine, maybe the NH2 -> OH conversions can be done at first, on phenylalanine. Then the decarboxylation may directly yield the phenethylalcohol(s).


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[*] posted on 29-5-2019 at 04:43


That phenylalanine> phenylethylamine>diotization route is an interesting Idea.

In fact, phenylethylamine is fairly cheap itself so you might even be able to save a step.

I've seen it on Ebay as some sort of dietary supplement or alternative medicine or some such thing in 500 gram bags.





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[*] posted on 29-5-2019 at 06:26


In fact, I wanted to synthesise it by addition from simple benzyl/phenyl compounds, that’s why I didn't consider making it by taking away bits and pieces from something more complex. Thanks for suggesting that. I’m going to research a bit into this pathway too.
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[*] posted on 29-5-2019 at 17:59


Quote: Originally posted by DavidJR  
"Perfume component", sure.


It is missing a methyl group for it to be made into an amphetamine.




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[*] posted on 29-5-2019 at 21:33


I was gonna suggest the phenylalanine route but someone beat me to it.

For the OTC source of styrene if your interested, its not in any paint thinner as far as im aware.
Its used for PVC, i believe as some kind of adhesive or plasticizer, we have some at work that we never use and i can get you an exact product label tomorrow.

If you were to opt for the route using styrene then you would have to epoxidize the double bond and then hydrolyse this with H2SO4 (don't quote me on this working), if it does work then you should still end up with a small amount of the more substituted alcohol.
If H2SO4 doesn't work then a lewis acid would instead have to be employed.

There was a reference floating around about H2SO4 working specifically on styrene oxide to produce the less substituted alcohol but i haven't a clue where it is.




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[*] posted on 29-5-2019 at 21:41


Haven't people cracked polystyrene to get styrene on this very forum?

yeah: http://www.sciencemadness.org/talk/viewthread.php?tid=88675#...




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