Sciencemadness Discussion Board - benzyl methyl ether

benzyl methyl ether

Fery - 30-5-2023 at 06:58

Hi guys,
I was pleased by the amazing scent of Lilac (Syringa vulgaris) in blossom so I searched internet and found the contents of its scent here:
https://www.bojensen.net/EssentialOilsEng/EssentialOils17/Es...

Quote:

(E)-ocimene to be the major component, and the most characteristic components to be the furanoid terpene aldehyde 'lilac aldehyde' and the corresponding alcohol (four diastereoisomers each), benzyl methyl ether, 1,4-dimethoxybenzene (hydroquinone dimethyl ether) and indole. In fact the diffusive aura of lilacs in full bloom is highly influenced by the compound benzyl methyl ether. This simple but rare chemical has an intense fruity-etheral odor, reminiscent of the top note in ylang-ylang oil

The hydroquinone dimethyl ether has only hay / mown grass / green scent and I do not plane to synthesize it. If someone synthesized it and the scent is worth to smell it, please let us know your experience.
http://www.thegoodscentscompany.com/data/rw1004451.html

So I decided to focus on benzyl methyl ether
http://www.thegoodscentscompany.com/data/rw1007261.html

Quote:

Odor Type: fruity ethereal ylang green floral hyacinth

In the above bojensen link, there is an information:

Quote:

As almost nothing is published on benzyl methyl ether, a note may be relevant concerning the small-scale synthesis of an olfactory pure quality of this odorant. Although the straightforward method would be from benzyl chloride and a surplus of methanolic sodium methoxide, this results in a product contaminated by an obnoxiously smelling impurity. Instead, benzyl alcohol should be methylated in methanol under mild conditions using an acidic catalyst and a water-removing agent (personal experiments).

There is wonderful detailed synthesis of diethyl ether on the forum here:
http://www.sciencemadness.org/talk/viewthread.php?tid=9747

But using H2SO4 should polymerize benzyl alcohol:
https://www.vedantu.com/question-answer/benzyl-alcohol-with-...

The bojensen method using acid catalyst and entrainer to remove reaction water is mystery for me then... I have dean stark trap, also various entrainers. I wouldn't use toluene as it could react with H2SO4. Maybe using aliphatic hydrocarbon like heptane or octane would be the way? But there is still that polymerization of benzyl alcohol problem (catalyzed by H2SO4). Also the azeotrope with water would distill below 100 C and for the ether formation the temperature 140 C is necessary (though maybe the reaction could have such a temperature and the vapor will escape overheated similarly like in diethylether synthesis where b.p. of diethylether is even much more lower than 140 C).

So due to doubts I will have to very likely start from benzyl chloride, which as bojensen stated introduces that lachrymator into the product and makes it unsuitable for use as an aroma (who would like to scent even traces of lachrymator???).

Then I found this:
https://sci-hub.wf/10.1021/ja01202a060

Attachment: ja01202a060.pdf (499kB)
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Quote:

Benzyl Methyl Ether.
Sodium hydroxide (6.9 kg, 172 moles) was mixed with 38 kg. (1190 moles) of methyl alcohol. Benzyl chloride (15.1 kg., 119 moles) was added at reflux temperature and refluxed nine to twelve hours. The product was distilled azeotropically with cyclohexanol (2400 g. of the ether with 750 g. of cyclohexanol). A 90% yield (10.7 moles, 13.1 kg.) was obtained.
It was noted that pure benzyl ethers formed peroxides extremely rapidly. A sample of benzyl methyl ether stored in a dark cabinet for six months was found to contain 2.6 equivalents of peroxidic oxygen per liter.
In most cases it was necessary to remove traces of halogen from the crude product by treatment with sodium in liquid ammonia or by azeotropic distillation. After treatment all materials were found to be halogen free by the Beilstein test.

Does someone know which of the compounds (benzyl chloride or benzyl methyl ether) makes an azeotrope with cyclohexanol? I found only these cyclohexanol azeotropes (you have to scroll down a lot of pages) and none of them is useful even in giving a clue with which the cyclohexanol forms the azeotrope (reactant lachrymator or product aroma)
http://www.homepages.ed.ac.uk/jwp/Chemeng/azeotrope/CC.html
Suppose I correctly is it benzyl methyl ether (the product) as the y. 1947 article uses the ratio 2400 g of the ether with 750 g of cyclohexanol?

I would like to synthesize the ether at the perfumery purity. I have a lot of powerful distillation columns / Raschig rings / variable ratio distillation heads. I would finally have a usage for my benzyl chloride. I have also the cyclohexanol (thanks chemship1978). I don't have the possibility to purify the product and remove benzyl chloride via NaNH2 (Na in liquid NH3).

Keras - 30-5-2023 at 07:06

I have something like that on my to do list, but the compound I was told smells like lilac is dimethylbenzylcarbinol which can conveniently be made by a Grignard from your benzyl chloride and acetone.

Fery - 30-5-2023 at 10:20

Hi Keras, thx for the idea, it is worth to try. This database reports its scent:
http://www.thegoodscentscompany.com/data/rw1004412.html

Quote:

2-methyl-1-phenylpropan-2-ol
dimethyl benzyl carbinol
alpha,alpha-dimethylphenethyl alcohol
Odor Strength:low
Odor Description:at 100.00 %. clean floral green rose cortex oily rhubarb
Luebke, William tgsc, (1982)

kmno4 - 30-5-2023 at 14:28

Quote:

Does someone know which of the compounds (benzyl chloride or benzyl methyl ether) makes an azeotrope with cyclohexanol?

The most possibly - none of these ones. I think it is simply H2O.
Besides, the article gives original paper, from which the procedure is taken. The procedure in english version looks like some patent s*it, maybe orginal german version is better (but I doubt

).
Anyway, it looks like classic Williamson ether synthesis.

Fery - 30-5-2023 at 20:38

Yes Williamson is the way I will have to go. Methanol + NaOH <-> Na methoxide + H2O. Benzyl chloride + Na methoxide -> Benzyl methyl ether + NaCl.
Removing water from the ether or benzyl chloride or their mixture could be easily done using cheap solid drying agents (CaCl2, Na2SO4, MgSO4 and so on).
If there is an azeotrope of benzyl methyl ether + cyclohexanol then why to add that cyclohexanol (lowering b.p. would make column distillation more efficient as the b.p. difference between azeotrope and benzyl chloride would be wider than without azeotrope where b.p. difference 10 C - b.p. benzyl methyl ether 169 C, b.p. benzyl chloride 179 C). How to finally separate the entrainer from the product as the distillation of azeotrope doesn't help (very likely washing with water)?
I'm concerned with benzyl chloride - how to remove it. Even traces of this lachrymator would destroy the nice scent of the ether. If I'm unable to remove benzyl chloride then the synthesis would be worthless to do.

Keras - 30-5-2023 at 21:42

There seems to be little choice apart from Williamson, yes (but see below). But yields are at most modest (~ 50 %, dixit Vogel). Unless more modern method using different products exist.

Probably traces of benzyl chloride can be removed by washing with dilute sodium hydroxide (or a solution of sodium carbonate?), which wouldn’t affect the ether. The benzyl alcohol would be washed with the water, in which the ether should be all but insoluble.

[Edit]

Of course, the disconnection point can be placed nearer to the benzene cycle. Ph-/-CH₂-O-CH₃ instead of Ph-CH₂-/O-CH₃. In this case, that means you could use chloromethyl methyl ether ClCH₂-O-CH₃ and use a Fridel-Craft alkylation to attach it to the benzene cycle. Chloromethyl methyl ether is not easy to synthetise. Maybe using dichloromethane and methoxide in a Williamson synthesis (although you risk obtaining dimethoxymethane)?

[Edited on 31-5-2023 by Keras]

kmno4 - 31-5-2023 at 02:06

Quote:

Methanol + NaOH <-> Na methoxide + H2O. Benzyl chloride + Na methoxide -> Benzyl methyl ether + NaCl.
Removing water from the ether or benzyl chloride or their mixture could be easily done using cheap solid drying agents (CaCl2, Na2SO4, MgSO4 and so on).

The simplest may be not the cheapest. I mean that preparing MeONa solution from Na and MeOH gives no water, so there is no need to remove it. Reaction of benzyl chloride with MeONa sol. is then much cleaner and small excess of methoxide will destroy any BnCl. Possibly some catalytic amount of iodide (KI) speeds up the reaction. It is good for small amount of the desired ether.
On kilograms-scale, KOH and MeOH can be cheaper, but not simpler.

I forgot to mention simple procedure of obtaining MeOK solution from K2CO3 and MeOH, described in some paper (DOI: 10.1021/je020012v). Worth testing for the ether preparation purposes.

[Edited on 31-5-2023 by kmno4]

Fery - 31-5-2023 at 12:17

kmno4 - great idea !!! thx !!!
the researchers synthesized all the ethers at scale of above 10 kg, so they did not use Na metal. I may try your suggested way (excess methanol + Na and then add BnCl so no BnCl stays unreacted). Also the methanol + K2CO3 route looks promising.

in fact, I already used K2CO3 in Will ether synth here, though it was something else:
https://www.sciencemadness.org/whisper/viewthread.php?tid=15...

[Edited on 31-5-2023 by Fery]

kmno4 - 31-5-2023 at 15:25

Yes, I have seen this post.
Of course, sodium/potasium benzylate + CH3I or Me2SO4 gives the same ether (at least in theory). It depends on what is at hand

I have just set a mixture: K2CO3+MeOH+BnCl(~2 g). I expect that reaction is slow at r.t. , I am going to check it after ~24 h if something changed. If not, small amount of KI will be added.
I am just curious if such simplified procedure works at all.

BTW.
BnCl is really not easy to hydrolyse, washing with NaOH sol. gives nothing at ~r.t., that is why removing of its traces may be problematic.

Fery - 31-5-2023 at 21:08

as you wrote, adding a little of KI should increase the speed of the reaction
BnCl + KI -> BnI which is much more reactive than BnCl
Btw there is a summer on the north hemisphere, I plane to close a reactor flask and put it into a warm but shaded place (e.g. in metallic box to the south wall of the house) for few months (maybe whole summer) occasionally opening it and trying to determine still present BnCl by a scent. I will certainly add KI, that's great idea which you suggested.

Fery - 1-6-2023 at 03:17

So I setup this experiment and I let it to stay in summer oscillating temperatures sealed and inside of metal box. The temperature oscillations may help in crystallizing KHCO3 (partial dissolution during day and crystallization during night).

1,0 g KI (6 mmol, catalyst) was dissolved in 100 ml methanol in 250 ml FBF and then added 31,0 g K2CO3 (224 mmol, big excess, freshly fused = 30 minutes in nickel crucible at 300 C). Flask stoppered and the content mixed for 30 minutes. Most of K2CO3 stayed undissolved as expected. Then 12,7 g benzyl chloride (= 100 mmol = 11,6 ml) added. Stopper greased, flask stoppered and clipped. Put inside metal box and to the south wall of the house for maybe the whole summertime.
Methanol used was quite dry, water content at most 0,05%, the performed analysis result done by the producer or distributor was 0,040%.
https://sklep-chemland.pl/en/odczynniki-chemiczne/odczynniki...
https://sklep-chemland.pl/media/products_pdf/48765_Cert_Meta...
https://sklep-chemland.pl/media/products_pdf/48765_PG_Metano...
benzyl chloride was pure quality, some older commercial sample.

[Edited on 1-6-2023 by Fery]

teodor - 1-6-2023 at 03:26

No comment about benzyl methyl ether yet (but I am following and quite interested) but if KHCO3 has the same stubborn character in regard to crystallization as NaHCO3 it could ignore any changes in a temperature.

[Edited on 1-6-2023 by teodor]

Fery - 1-6-2023 at 11:07

Figure I in the article posted by kmno4

25 C 0,001 mol KHCO3 / 1 L methanol
45 C 0,006 mol KHCO3 / 1 L methanol

20 C higher T and 6 fold higher solubility KHCO3
concentration of CH3OK almost the same around 0,5 mol / L

Attachment: je020012v.pdf (27kB)
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I hope KHCO3 will crystallize separately and won't cover K2CO3 to prevent it from further reacting.

kmno4 - 3-6-2023 at 17:15

Hm, it seems that this simple procedure works

I expected rather unchanged reagents....
My proportions:
10 g MeOH + 2,1 g BnCl + 6 g K2CO3 + 0,7 g KI (added after 24 h), temp. ~30 C, time 3x24 h.
A sample of evaporated solution (watch glass) gives not lacrymatory residue. Its odour strongly reminds me odour of ethyl benzoate, which is not too pleasant, at least for me (nauseous smell). Also very "distant echoes" of Et2O are smellable.

Keras - 4-6-2023 at 01:41

On the other hand, if you’re not faint-hearted, you can use your benzoyl chloride to get benzoyl peroxide with 12% H₂O₂.
If you‘re interested, see Vogel.

Fery - 4-6-2023 at 02:50

Yes I have almost 2 L of this nasty stuff. Luckily I found first good usage for me in the ether synthesis. I can get benzoyl peroxide pharma grade as it is used for treatment of some skin diseases. Benzoyl peroxide kills all bacteria, there is no possibility of resistance as it could develop for antibiotics in the treatment of acne. The same scabies, a lot of infestations resistant to modern cures, luckily no possibility to develop resistance against old good sulfur powder in the form of an sulfur ointment.

Pumukli - 23-6-2023 at 09:07

Entirely unrelated search a few minutes ago resulted this:

Attachment: benzoicesterelectroreductions.pdf (263kB)
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If I get it right electrolizing methyl- (or ethyl) benzoate in 50% H2SO4 diluted with MeOH or EtOH on Pb cathode yields the respective alkyl-benzyl ethers in a fairly good yield. Old paper, reputable author, probably works.

myr - 23-6-2023 at 16:13

Quote:

The hydroquinone dimethyl ether has only hay / mown grass / green scent and I do not plane to synthesize it. If someone synthesized it and the scent is worth to smell it, please let us know your experience. http://www.thegoodscentscompany.com/data/rw1004451.html

It's an interesting, pleasant smell. I think you can tell that it's adjacent to anisole, but it's still distinct. A long time since I smelled it. I don't remember ethereal notes but hyacinth fits. "Warm", "plastic-y", and sweet are words I wrote down. It reminded me of the laundry detergent my family used to use.
It's not a spectacular aroma, but the re-crystallization is nice. I would say it's more worth testing a methylation reaction system, or for further functionalization, than a target odor.

Fery - 24-6-2023 at 03:40

Anisole did not scent to me pleasant either natural, for me it had some "chemical" scent. Even phenol scented to me quite pleasant, but not the anisole.
Benzylmethylether should be pleasant according good scents company database.
The problem is to complete the reaction to 100% to remove all benzychloride (lachrymator).
The reaction proceeded already but I do not know at which extent. The flask is stoppered and clamped, I did not open it yet (to prevent introducing air moisture). But the solid K2CO3 reactant was quite heavy and prone to settle on the flask bottom. Now there is a lot of lighter white solid, very likely much tinier crystals of KCl and KHCO3, on swirling the flask they float readily and settle only after a lot of time. K2CO3 which was put into flask on the beginning of the experiment settled in few seconds. Now K2CO3 cannot be observed due to milky suspension of lighter smaller crystals of KCl / KHCO3. So the reaction seems to proceed, but the most important thing is whether all the benzylchloride will be reacted or not. The other question is whether benzylchloride just did not hydrolyze to benzyl alcohol in the alkaline solution of K2CO3 in methanol.
I try to swirl the flask in hand every day. It is in black tin on black metal sheet and during shiny days the temperature reaches something like 50 C... I try to swirl it when its temperature raises as then K2CO3 is more soluble than in cold so swirling warm flask should dissolve K2CO3 (which was initially used in slightly more than 2-fold excess).

kmno4 - 24-6-2023 at 05:44

The paper about electroreduction of organic matters is interesting, but badly OCRed. Improved version, with German OCR, ready for G-e translator -> in attachment.
EDIT
Complete setup, mentioned in the paper, is described in reference [3]. Also in attachment.
BTW

Quote:

The other question is whether benzylchloride just did not hydrolyze to benzyl alcohol in the alkaline solution of K2CO3 in methanol.

No water = no hydrolysis

Attachment: electroreductions_2.pdf (96kB)
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Attachment: 281-288.pdf (232kB)
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[Edited on 24-6-2023 by kmno4]

kmno4 - 25-6-2023 at 12:29

Just to end what has been started :

After several days standing (just no time for playing with it), the flask was uncapped and set to free evaporation at r.t. When most of MeOH evaporated, some water was added to dissolve K salts.
Two layers was formed: organic upper one, slighly brownish and water lower one, with no colour.
Most of water pahase was removed and some fresh water added again. This time layers separation was no so clear, because density of BnOMe not differs greatly from H2O density. Some NaCl was added, giving better separation. The organic layer was still brownish, but it was caused by... iodine. Adding some Na2S2O3 gave colorless ether layer. The article mentioned above says the truth and formation of the ether peroxide is relatively quick. About 1,8 cm3 of organic liquid was obtained. Its scent now is not so similar to benzoate ester, but reminds me more odour of BnCl self (but not lacrimatory), with some phenolic and Et2O note. Generally, not very pleasant, strong chemical odour, but not very persistent.

Fery - 4-7-2023 at 02:06

I confirm. I opened the bottle and no lachrymation. I will process the methanolic solution further. For me the scent is very strong and very pleasant, but now it is diluted in methanol so its concentration is approx 10%.
The reaction could be maybe done in few hours under magnetic stirring + reflux and drying tube on top of condenser. Seems the reaction of anhydrous K2CO3 with methanol produces potassium methoxide readily. Addition of KI could make reaction faster as kmno4 suggested (turning BnCl into more reactive BnI) and it is also a good indicator for peroxidation (mine solution is only slightly yellow as in the flask there was only about 100 ml of air so circa 20 mg of O2 present). I will maybe evaporate methanol not in air but under reduces pressure to minimize peroxidation and maximize yield.

Fery - 21-7-2023 at 10:03

After 6 weeks there was no lachrymatory scent of benzylchloride. Middle weight stirbar was added, the flask attached to water aspirator pump and swirled in hand to evaporate methanol at vacuum, it quickly became very cold so was submerged in a bucket with 40 C warm water while continuing swirling until methanol evaporated resulting in final thick mass (that's why the stirbar was added, without it the K salts won't be moving but just attached/sticked to bottom or walls).
100 ml water was added which dissolved inorganic salts and organic upper layer separated in separatory funnel.
Washing with 5 ml of saturated Na2S2O3 did not change the color of the organic layer, draining it into previously separated water bottom layer did not do anything either. Seems not to be peroxides / I2 present (thanks to removing methanol using vacuum). No need to wash with Na2S2O3 in this workup method.
Weight 9,0 g = 74% yield (??? loses due to vacuum evaporation ???)
Crude product was dried with anhydous Na2SO4, it lost its cloudiness and become clear but still yellowish color persisted. Later a little of anhydrous CaCl2 was added (maybe unnecessary, with a hope of binding last traces of benzyl chloride if they were present at all).
weight 8,7 g = 71% yield
Molar mass 122,167 g.mol-1
It was not vacuum distilled due little amount of it.

An attempt to recover product by steam distillation of water phases and washings was made, 15 ml distillate collected with little of product (totally like 1-2 drops), next 10 ml distillate clear and without any scent of the product. Not worth to do it. But maybe steam distillation is a good idea of product purification (as an alternative to vacuum distillation). Reduces the risk of peroxide explosion in the distillation flask. I wouldn't distill the product at atmospheric pressure due to peroxide formation and quite high boiling point (only vacuum distillation or maybe steam distillation).