Maui3
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Synthesis and Smell of 2-Phenylethyl chloride
I know the same reaction (just with benzyl alcohol to benzyl chloride) has been convered a lot, but I still wanted to share my synthesis of phenethyl
chloride by the same method. 2-Phenylethanol (my starting material) is not soluble in the 37% HCl - so it might be hard to seperate the
phenethylchloride from unreacted 2-phenylethanol. I didn't care that much about unreacted 2-phenylethanol, so I did not remove it.
Firstly, 25 g of 37% HCl was added to an erlenmeyer flask containing 15 g 2-Phenylethanol. The to mixtures did not dissolve in one another. The
mixture was refluxe at 120 C for 1 hour under strong magnetic stirring. The mixture was thereafter cooled and dilute sodium carbonate solution was
added VERY SLOWLY. The 2-Phenylethylchloride (upper layer) was sucked up by a pipette and dried over calcium chloride.
Now for the fun part! I could not find any info about the smell of phenylethylchloride, so here is my evaluation: It smells kind of like cress and
honey - and if you take a big wiff of it, it smells very spicy.
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Dr.Bob
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You likely have some styrene in the mixture, due to elimination of HCl/H2O from the ethanol derivitive. Benzyl halides can't form alkenes, so they
are very stable, compared to phenethylhalides. I have done reactions with those, and they often form styrenes as byproducts.
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Maui3
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Okay. Thanks for letting me know. Do you still think I have some phenethylchloride in there? Also, is it unstable to moisture or oxygen?
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Texium
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I highly doubt that you have much of your desired product at all.
These conditions (strong acid, protic solvent) promote an SN1 or E1 reaction. These mechanisms require the formation of a carbocation intermediate. In
the benzyl case, that’s great, because the benzyl carbocation is very stable and long lived. It also can’t undergo an E1 elimination, so its only
option is SN1. The phenylethyl case is entirely different. Regular primary carbocations are very unstable, and will rearrange if possible. So what
will most likely happen will be a hydride shift from the benzylic carbon to the primary carbon to place the positive charge on the benzylic carbon.
Then it can undergo E1 to form styrene as Dr. Bob noted, or if it were to undergo SN1, you’d get 1-phenyl-1-chloroethane instead of your desired
isomer. Pathways for formation of your desired product are limited and unfavorable under these conditions.
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Dr.Bob
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I think you can get some of the desired product, although I have cheated and bought my 2-phenethylchoride, but I am also thinking that the reaction
conditions may favor elimination more then reaction, unless you are very careful with the solvent, base, temp, and conditions, as that was what I have
to optimize to make my reaction work, albeit not in great yields. My product was a chiral, sterically hindered complex target towards an arthritis
drug, so not very much comparable to whatever you are doing. But Texium is right that the reaction may provide multiple products. If there is a
more stable intermediate, that is usually the route of least resistance. For a few stable compounds, an SN1 works well, benzyls and t-butyl being
great examples, but in this case the reaction will likely go other paths.
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Keras
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Indeed, for 2-phenethylbromide I would start from styrene and brominate with NBS or bromine under UV light.
I’m not sure what reagent could led to an anti-Markhovnikov addition of chlorine. Hydroboration of styrene gives 2-phenethylethanol, but that’s of
no use here.
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Maui3
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Thank you all for the answers. I should really have thought about that before posting on here.
Dr. Bob, forgive me for asking this, but you say you bought the 2-phenethylchloride. Have you smelled it? I know smell is not a good indicator of the
presence and concentration of a compound, but I am still quite curious to hear if your phenethylchloride smelled cress-like.
I did find this paper saying phenethyl bromide can be made from HBr and Phenylethanol - which is quite similar to what I did. https://cdnsciencepub.com/doi/pdf/10.1139/v54-132
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Keras
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If I can hazard a guess, I would say that phenethyl chloride would hydrolyse to phenethyl ethanol and HCl on contact with nose's cell wall, a bit the
same way acetic anhydride does, giving rise to a scent of roses probably somewhat muffled by the pungency of HCl.
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Texium
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I decided to try this procedure myself today on the side at work and get an NMR of the result. I ran it on a 1 gram scale and extracted the product
with diethyl ether since it was a little more difficult to separate from the aqueous layer on the smaller scale. I also dried it with
K2CO3 instead of CaCl2 so that residual HCl would be removed. Otherwise I did everything the same as Maui3 described.
The verdict is...
![Screen Shot 2025-01-09 at 4.10.50 PM.png - 183kB](http://www.sciencemadness.org/talk/files.php?pid=698275&aid=104367)
It's all starting material. No sign of styrene or either alkyl chloride. The unlabeled peaks at 3.5 and 1.2 are extraneous diethyl ether because I
didn't have it on the vacuum long enough.
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Maui3
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That's a good theory Keras. I do think it smelled much different than HCl and phenethylalcohol, but I mean.. your theory is still better than a simple
smell-test.
Wow Texium, thank you for doing that! I geuss that solves the mystery. I still have a few questions though:
- Why do I think the odor is that much different? It really didn't smell like phenylethanol or HCL, or both.
- Why does this paper say it was sucessfull with HBr to get alkyl bromide: https://cdnsciencepub.com/doi/pdf/10.1139/v54-132?
- I assume you worked in your fume hood, but did you get a whiff of it? How would you describe it?
I can't argue with Texium's NMR - but the smell still confuses me.
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Keras
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I would expect the Br from HBr to add at the 1-position because of rearrangement of the carbocation.
This is different from direct bromination by Br₂ under UV light or NBS, which form bromine radicals Br•. These radicals are ‘acroselective’,
they add at the terminal carbon because this structure is more stable. See, for example here.
[EDIT: Add textbook excerpt]
[Edited on 10-1-2025 by Keras]
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Texium
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HBr will produce the desired product because
1. Br- is a significantly stronger nucleophile than Cl-
2. HBr is a stronger acid than HCl, so more of the alcohol will be protonated to produce a better leaving group.
The combination of these factors allow for an SN2 substitution to occur that won’t happen with HCl.
As far as the smell goes, I didn’t smell it until after drying with potassium carbonate, but after that it just smelled like phenylethanol. Maybe
try doing the same with yours and see if the smell changes.
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Maui3
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Thank you so much, Keras and Texium, for the thorough explanation! I truly appreciate it!
I really wish I had access to NMR (or a similar technique) to analyze my sample. To me, it has a distinct smell that's very different from
phenylethanol. If I hadn't seen your NMR results, Texium, I would have been 100% convinced it was a different compound—at least, as certain as one
can be from just the smell.
I even had a few friends take a sniff, as you do, and they also agree it smells quite different.
Unfortunately, I don’t have K2CO3 on hand to test your theory.
I have a feeling I come across a bit presumptuous, since you did my exact procedure and analyzed it - and I still keep feeling that my sample must
contain a compound different than my starting material. It's just that I can't see how the same compound could smell that different.
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Maui3
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I will research it a bit further, but I am considering doing a silver nitrate test to my sample, to see if it is an alkyl halide.
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Texium
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Keep in mind that if you have HCl in your sample, that test will give a false positive. Sodium carbonate would also work. If you don’t have that,
heat some bicarbonate in the oven.
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Maui3
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Texium, are you saying sodium carbonate could work instead of silver nitrate or the K2CO3? I assume you mean the K2CO3.
[Edited on 10-1-2025 by Maui3]
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Texium
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Yes, instead of potassium carbonate. It will neutralize HCl to see if that alone changes the perceived smell and also prevent your silver nitrate test
from giving a false positive.
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Maui3
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I'll do that then.
Do you think I could test with sodium metal too? If it is the alcohol it should produce H2, and if it is the alkyl chloride it should not produce any
H2. I could maybe find a way to measure how much H2 generated, as there might be unreacted alcohol in there regardless of the reaction worked or not.
I am not in the mood to synthesize silver nitrate and get my lab-bench stayed black again, so I prefer a test with sodium metal :p
I geuss the sodium metal test is not as precise, since it could be a styrene too, or there could be small amounts of unreacted alcohol in my sample..
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Maui3
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Just did the sodium-test today. I'll do the silver nitrate another day.
2-Phenethylalcohol bubbled slightly when reacted with sodium.
My sample (of hopefully 2-phenethyl chloride) did not.
I did it on a really small scale, so it was hard to see. But I never observed a bubble from my sample.
I geuss this isn't so definitive, so I'll do the silver nitrate soon.
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Dr.Bob
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The smell could come from a very small amount of either 1 or 2-phenylethylchloride. I do understand that the HBr method might work better, there are
also many other ways to make bromides, so there may be other ways to make it. But all will still require careful reactions to be used as an
alkylating agent.
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Maui3
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Yes. I think I'll make the bromide instead.
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kmno4
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2-Phenylethanol can be separated from corresponding chloride by conc. H2SO4 treatment (r.t.) - the alcohol dissolves, the chloride does not. Just 5
cents remark for interested.
Слава Україні !
Героям слава !
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