Sciencemadness Discussion Board - Pathways to phenethyl alcohol

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.

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]

laserlisa - 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.

Pumukli - 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]

Keras - 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?

Keras - 28-5-2019 at 05:25

(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]

Pumukli - 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!

Keras - 28-5-2019 at 06:24

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?

CuReUS - 28-5-2019 at 07:41

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#...

Keras - 28-5-2019 at 11:39

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.

SWIM - 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]

CuReUS - 28-5-2019 at 19:53

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

Besides, I have no idea how expensive is BH₃ in THF

There is something called "google"...

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

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]

SWIM - 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]

Keras - 28-5-2019 at 23:50

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.

Besides, I have no idea how expensive is BH₃ in THF

There is something called "google"...

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]

PirateDocBrown - 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]

Keras - 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

Pumukli - 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).

Attachment: aminetoalcohol.pdf (101kB)
This file has been downloaded 339 times

SWIM - 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.

Keras - 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.

VSEPR_VOID - 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.

Assured Fish - 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.

DraconicAcid - 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#...

Assured Fish - 29-5-2019 at 22:56

Quote: Originally posted by DraconicAcid

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

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

Yup. Also UC235 made a video on it.
Although im pretty sure the process stinks to high heaven just based on the fact that polystyrene always contains other additives, someone could do it that way if they wish, as 350°C isn't too hard to reach with heating tape or a burner.
Id just pitty the fool who tried without a fumehood.

Keras - 30-5-2019 at 08:47

350 °C could even be reached with a good heating mantle. But I’m surprised he didn't get more tar.

But using styrene to epoxide it (with peracetic acid) is more or less the same than using oxirane from the get go. It seems that oxirane can be produced in one step from ethylene by bubbling it in a strongly basic bleach solution. The hypochlorite oxidise the ethylene to 2-choloroethanol which is then dehydrated into oxirane by the base. Besides this reaction can be conducted around 0°C which would avoid the formation of oxirane gas. It’s hard to find a reference, but this Japanese patent seems to indicate so…

CuReUS - 30-5-2019 at 09:45

as 350°C isn't too hard to reach...

its more like 2000'C

H2SO4 working specifically on styrene oxide to produce the less substituted alcohol.

http://www.sciencemadness.org/talk/viewthread.php?tid=22421&...

the only way to make 2-phenylethanol from styrene oxide is with reducing agents like Pt,Pd,SAH,DIBAL-H and LiH -http://www.escience.cn/system/file?fileId=96971

using NaBH₄-https://www.tandfonline.com/doi/abs/10.1080/0039791090307960...

but this route is cumbersome and goes against the OP's desire for an easy method

-http://www.sciencemadness.org/talk/viewthread.php?tid=22421&...

But I’m surprised he didn't get more tar.

You wouldn't be if you had watched the video I sent you

Quote:

Besides this reaction can be conducted around 0°C which would avoid the formation of oxirane gas.

but you have to distill it later to get pure oxirane

...

btw,I found a ref for the anti-markonikoff bromination of styrene

clearly_not_atara - 30-5-2019 at 10:41

https://www.tandfonline.com/doi/abs/10.1080/00397911.2017.12...

Attachment: bhatt2017.pdf (658kB)
This file has been downloaded 378 times

Keras - 30-5-2019 at 11:39

Quote: Originally posted by clearly_not_atara

https://www.tandfonline.com/doi/abs/10.1080/00397911.2017.12...

Thanks a bunch for that! Serendipitously I had just ordered zinc powder with my latest batch of magnesium turnings. So I’ll be able to test that out next time I can put my hands on my glassware. Meanwhile I should find a way to get paraformaldehyde from the 40% formaldehyde solution I have.

SWIM - 30-5-2019 at 13:29

Styrene thinner is available in California in shops that sell fiberglass making materials.
I think it is used at times to thin the resin.

What I know for certain is it is on the shelf in cans at Tap Plastics in San Mateo, and since California has serious environmental regulations I would assume its available in most of the US.

I've seen it online too. It is 90% styrene monomer and $25 a quart from Fiber Glast Developments corp. (That's not a typo)
They are in Ohio.

draculic acid69 - 30-5-2019 at 18:07

Diazotise phenethylamine with nano2 and HCl.its that simple.i think.
No need to fuck with etO.

Assured Fish - 30-5-2019 at 21:26

as 350°C isn't too hard to reach...

its more like 2000'C

No, its more like 400*C : https://www.youtube.com/watch?v=6tEs7P6UUVQ
https://en.wikipedia.org/wiki/Depolymerization

H2SO4 working specifically on styrene oxide to produce the less substituted alcohol.

http://www.sciencemadness.org/talk/viewthread.php?tid=22421&...

the only way to make 2-phenylethanol from styrene oxide is with reducing agents like Pt,Pd,SAH,DIBAL-H and LiH

Yea i should know better, im gonna put that down to a brain fart.

Well if anyone is interested, (which i don't think they are).
The styrene at my work is this stuff: https://www.amcsupplies.com.au/manuals/Styrene%20Monomer%20-...

Probably only available in australia and new zealand, but im sure other similar products are available elsewhere.
Apparently it has a hell of a lot more than one use, as it solvates a few other plastics like PVC.
Or its just used as a generic adhesive or in making ABS resins.
It should be available in virtually any westernized part of the world.
It just won't be the easiest to track down.

Keras - 31-5-2019 at 00:31

Quote: Originally posted by draculic acid69

Diazotise phenethylamine with nano2 and HCl.its that simple.i think.
No need to fuck with etO.

I'd need to make phenethylamine first :p

I think I’ll try the zinc route first, seems challenging… although it takes a bit of time.

For styrene, I surmise it’s been registered in the European REACH directive annex XVII (can’t check out, the related website seems to be dead) and phased out in commercial products, to be replaced by the less noxious ethyltoluene/vinyltoluene, a bit the same way benzene has been replaced by toluene, which is not as carcinogenic.

Also this patent claims to make styrene out of toluene and methanol.

[Edited on 31-5-2019 by Keras]

Waffles SS - 31-5-2019 at 01:28

My advise:
"Dont trust to Indian or Iranian or even Chinese articles"
(unfortunately i did this mistake many times)

I have experience on making Phenethyl alcohol from Phenylacetic acid ester by Bouveault-Blanc reduction and this is easiest and cheapest method.

Suggested method for synthesis Phenylacetic acid is Willgerodt-Kindler reaction from Styrene.

I attach reaxys search of all possible way for synthesis Phenethyl alcohol

Attachment: Phenethyl alcohol.pdf (2.3MB)
This file has been downloaded 1513 times

[Edited on 31-5-2019 by Waffles SS]

Keras - 31-5-2019 at 03:42

Quote: Originally posted by Waffles SS

My advise:
"Dont trust to Indian or Iranian or even Chinese articles"
(unfortunately i did this mistake many times)

I don't trust Chinese material in general

Quote: Originally posted by Waffles SS

I have experience on making Phenethyl alcohol from Phenylacetic acid ester by Bouveault-Blanc reduction and this is easiest and cheapest method.

Suggested method for synthesis Phenylacetic acid is Willgerodt-Kindler reaction from Styrene.

I attach reaxys search of all possible way for synthesis Phenethyl alcohol

Thanks for that. I'm still amazed that most of these reactions proceed from something more complex and take out a moiety to form phenethyl alcohol, as if it was impossible to synthesise from simplier molecules.

draculic acid69 - 31-5-2019 at 04:09

Why would you need to make phenethylamine just buy it off eBay or alibaba.by the time you buy phenylalanine and decarboxylation catalyst and work it up,or if your making it from phenethylbromide(unlikely) it can't possibly be cost effective to make it rather than buy it.

clearly_not_atara - 31-5-2019 at 08:47

Indian research is certainly suspect, except the best Indian universities. But the formation of benzylzinc reagents and the addition of benzylzinc to aldehydes are both multiply attested. Reaxys showed another version of this reaction that uses water as a solvent with catalytic CdCl2 and InCl3:

https://www.thieme-connect.com/products/ejournals/abstract/1...

There may be other versions that use BnBr instead of BnCl to generate the BnZnX, since the bromide is usually better for these reactions.

CuReUS - 1-6-2019 at 09:32

Quote: Originally posted by draculic acid69

Why would you need to make phenethylamine just buy it off eBay or alibaba

In that case,the OP could just buy phenylethanol itself