Author Topic: Methylating agent sources?? (Read 1306 times)

Sedit · « **Reply #20 on:** May 05, 2009, 12:15:26 AM »

Discussion of insitu bromomethane for methylenation I found over at the hyperlab.

https://www.hyperlab.info/inv/index.php?act=ST&f=17&t=29370&s=7fa0f7db842ab9346e502df479acd792

Persona speaks english so you should be ok understanding the discussion.

Vesp · « **Reply #21 on:** May 05, 2009, 12:27:40 AM »

I am unable to view it for some reason (both in FF and IE) Could you perhaps post the important discussion here? I will try later if it is to difficult to get the useful information.

Sedit · « **Reply #22 on:** May 05, 2009, 12:35:18 AM »

You may have to register over at hyperlab Im unsure though. Ill see what I can dig up for you.

Sedit · « **Reply #23 on:** May 05, 2009, 01:01:57 AM »

Upon further inspection Im not sure if this is the reaction desired. This is a bromo or chloromethylation and is most effective on aromatic rings. If im not mistaken they are shoting for Blancs chloromethylation and what there attempting is an old procedure posted by Nicodem over at the hive some time back. Here is the post from the hive at the very lest,

Post 514652 (Nicodem: “Brominations in a two phase system”, Chemistry discourse)

2-bromo-1,4-dimethoxybenzene.
In a 1L two neck flask with a thermometer and a dropping funnel was added 50g of 1,4-dimethoxybenzene (362mmol), 38.4g sodium bromide (369mmol), 100ml of water, 165ml 35% sulphuric acid and 200ml methylenechloride. The flask was set on an ice bath and magnetic stirring was applied. When all the solids dissolved there was added trough the dropping funnel 45ml of about 30% hydrogen peroxide (388mmol) with such a speed that the temperature of the reaction mixture stayed below 20°C. About an hour and a half was needed and then the reaction was left stirring for a further half an hour. The water phase was carefully decanted, 200ml water added, mixed and again decanted. This was repeated once more and then also with 100ml 5% sodium bicarbonate and again 200ml water. The methylenechloride solution was put into a 500ml flask trough a separation funnel in order to remove any remaining water and then the methylenechloride recycled by distillation. The water cooled condenser was removed and the two ends connected in a short path distilling apparatus. Vacuum was then applied and the contents distilled at a higher temperature. The first 3ml of distillate contained some 1,4-dimethoxybenzene as shown by the formation of some crystals and were thus discarded. The distillation was stopped before the third fraction of dibrominated products began to come over. The distillate containing 2-bromo-1,4-dimethoxybenzene as a golden yellow oil weighted 64.35g (82%). From the dark solid remains in the flask, 1.4g of a colorless crystalline material, presumably 2,5-dibromo-1,4-dimethoxybenzene, was isolated by recrystallization from ethanol.

Douchermann · « **Reply #24 on:** May 05, 2009, 01:32:10 AM »

My appologies good sirs. I just re-read and realized I didn't even post the link about the production of tosyl chloride (or the analogous procedure I should say). No wonder there was confusion about where the aminobenzotrifluoride came from. Here is the link:
http://www.orgsyn.org/orgsyn/pdfs/CV7P0508.pdf

Quote from: Douchermann on April 16, 2009, 07:29:44 AM

Possibly. Alcohol + HCl + lewis acid will yeild the appropriate alkyl chloride. A lewis acid commonly employed for this is ZnCl2, so it might be worth a shot, by adding a couple grams of ZnCl2 to the reaction. Give it a shot, if you want.

Alright guys, after some reading around, I believe methyl tosylate is quite in reach. It wont be an easy procedure, however methyl tosylate is quite powerful, yet very safe (as compared to MeI and DMS). Below is the preparation of butyll tosylate from tosyl chloride and butanol:
http://orgsynth.org/orgsyn/prep.asp?prep=cv1p0145
obvious substitution of methanol for the butanol does yeild the correct product:
http://www.sciencemadness.org/talk/viewthread.php?tid=11004#pid133307

As for tosyl chloride, it can be prepared from quite OTC materials, if you substitute aniline for aminobenzotriflouride.
(tolune ---> nitrotoluene ----> aniline)
SO2 can be generated from sodium dithionite, which is 'RUST RAZE', a rust remover available in grocery stores. Just add HCl. It's not the most favorable route, but its a route regardless, and it's a methylating agent that works quite well and is no where near as toxic.

Vesp · « **Reply #25 on:** May 12, 2009, 03:09:56 AM »

Oh silly me, according to Orgsyn sodium methyl sulfate can be used to make methoxybenzene from phenol or its salts.

Quote

Anisole can be prepared from phenol or its salts by the use of the following methylating agents: methyl chloride;1 sodium methyl sulfate;2 methyl alcohol in the presence of thorium oxide;3 methyl alcohol and ?-naphthalenesulfonic acid4 or potassium hydrogen sulfate5 or boron fluoride;6 dimethyl sulfate;7 and methyl ether and boron fluoride.8

The bold statement really interests me though. I wonder if that could be a one pot synthesis from sodium phenol, sodium bisulfate, and methanol?

Goldmember · « **Reply #26 on:** July 07, 2009, 01:17:54 PM »

Go green

Urea, methanol, polyphosphoric acid -> DMC
Autoclave yeah!

Synthesis of dimethyl carbonate from urea and methanol using polyphosphoric acid as catalyst
doi:10.1016/j.molcata.2005.06.001

A new process was proposed for the synthesis of dimethyl carbonate (DMC) from urea and methanol in a batch operation. Polyphosphoric acid (PPA) was used as the catalyst and the absorbent for the ammonia, which was produced during the reaction. The effects of various operation conditions, such as reaction temperature, pressure, reaction time and the molar ratio of the reactants were investigated in the terms of DMC yield. The experimental results indicated that the optimal reaction conditions were the molar ratio of methanol/urea of 14, reaction time of 4 h, reaction temperature of 413 K, PPA/urea mass ratio of 1 and initial pressure of CO2 of 0.8 MPa, respectively. The DMC yield of 67.4% was obtained in the optimal reaction conditions. The by-product, ammonia was also used as a starting material of a useful fertilizer in the proposed process.

POSEIDON · « **Reply #27 on:** July 12, 2009, 05:23:55 AM »

Hey look this pdf about halides , think in methyl iodide

Vanadium · « **Reply #28 on:** August 03, 2009, 07:07:14 AM »

Quote from: Vesp on May 04, 2009, 05:24:07 AM

Then from there, just do a duff reaction, using the typical boric acid, glycerol and hexamine. React with acid, and then you should have 3,4,5-Trimethoxybenzaldehyde.

Or the typical AcOH and hexamine

It may just be preferable to leave the phenol alone before the Duff because OH>OR in terms of activation of the benzene ring.

Quote from: POSEIDON on July 12, 2009, 05:23:55 AM

Hey look this pdf about halides , think in methyl iodide

Thanks for that paper! I don't want to turn this into a safrole thread though, so...

If we're looking for alkylating agents I would definitely prefer the methyl sulfate. Regarding this, while I'm not sure about your hypothetical procedure for M-SO4-Me, Vesp, one could easily modify this: http://www.sciencemadness.org/talk/viewthread.php?tid=1113 to get the desired product.

Goldmember · « **Reply #29 on:** August 15, 2009, 09:20:47 AM »

DimethylSULPHITE cops a mention here.

"Process for the alkylation of phenolic compounds"

http://www.patentstorm.us/patents/4453004/description.html

Formula409 · « **Reply #30 on:** September 01, 2009, 09:43:40 AM »

Hi there

I have this:
http://www.sciencemadness.org/talk/viewthread.php?tid=11580#pid143066

And this:
https://www.hyperlab.info/inv/index.php?act=ST&f=17&t=28895&s=34957a25d5da9fd745511f5ccdc214a0

Quote

O-ethyl-eugenol. In a 250 ml flask there was added 60 ml clove oil (about 360 mmol of eugenol), 60 ml diethyl oxalate (438 mmol), 60 g K2CO3 (438 mmol) and the mixture magnetically stirred and heated on an oil bath with a short air cooled reflux condenser, thus allowing for the water vapors to escape. The mixture formed a yellow slurry. When the oil bath temperature reached 120°C there started the evolution of CO2 and steam. The heating was continued for further two hours, meantime allowing the temperature to slowly rise up to 190°C. When the reaction mixture cooled to about 80°C, there was added 180 ml water and the flask shaken until most of the solids dissolved forming two brown layers (with a little tar at the bottom). The organic layer was separated, washed 3 times with 80 ml 6% NaOH(aq) and 30 ml brine. The resulting dark oil was distilled in the vacuum of an aspirator. About 1 or 2 ml of some liquid came over up to 130°C (probably some remaining diethyl oxalate) which was discarded. Then the product distilled at 130-140°C, resulting in 40.5 g (58%) of a clear, colorless oil.
(Additional information: The reaction does not proceed with Na2CO3 as a base!)

Formula409.

Baba_McKensey · « **Reply #31 on:** September 26, 2009, 08:41:57 PM »

http://www.sciencemadness.org/talk/viewthread.php?tid=1261&page=4#pid157397

US patent 2490842 Anisole manufacture
Column 2 lines 6+
The methyl sulfate may also contain a metal substituent on the sulfate radical, as in the case of sodium methyl sulfate or potassium methyl sulfate, it may contain an ammonium substituent as in the case of ammonium methyl sulfate, or it may contain a hydrogen substituent as in the case of methyl acid sulfate.

US patent 2529887 Process for the preparation of anisole
Column 5 lines 30+
Suitable methylating agents for phenol include, for example, a methyl sulfate having the methyl group directly attached to the sulfate radical such as dimethyl sulfate, sodium methyl sulfate, potassium methyl sulfate, ammonium methyl sulfate, or methyl acid sulfate; also methyl halides such as methyl chloride, methyl iodide, and methyl bromide; and organic methyl esters such as methyl acetate.

Sedit · « **Reply #32 on:** September 26, 2009, 09:03:17 PM »

Ammonia Methylsulfate can be used as a methylating reagent?

. And all this time I have been isomerizing it to Methylamine bisulfate... Huh go figure.

no1uno · « **Reply #33 on:** September 30, 2009, 10:08:31 PM »

Apparently Methyl Methanesulfonate can be used as a fucking handy methylating agent - need to find some ref's on it's use (MP 20C, BP 200+C), anyway, here is it's preparation

madprossor · « **Reply #34 on:** November 28, 2009, 10:43:02 AM »

Quote from: no1uno on September 30, 2009, 10:08:31 PM

Apparently Methyl Methanesulfonate can be used as a fucking handy methylating agent - need to find some ref's on it's use (MP 20C, BP 200+C), anyway, here is it's preparation

thanks for the awesome Mesyl Chloride preparation!!! (i don't understand how you would make Mesyl Chloride into methanesulfonic acid though, how is that step done?)

mesyl chloride is used industrially for preparing dialkyltryptamines from indole-3-ethanol. like in the patent for sumatriptan. i found a good procedure here-
www.patentstorm.us/patents/5567824/description.html

could come in handy if urishibara with a dean-stark doesn't work out. bromination is the hundred year old alternative.

hmm, mesyl chloride inhalation kills rats at 25ppm in 4 hours. at least it's not a mutagen too. it's vapor pressure is about 1/10 that of water, which makes sense with a boiling point of 160C. so it's nasty but at least it's not highly volatile.

madprossor · « **Reply #35 on:** November 28, 2009, 11:45:46 AM »

sorry for the double post. here's an excellent alkyl halide preparation from orgsyn-

http://www.orgsyn.org/orgsyn/default.asp?formgroup=basenp_form_group&dataaction=db&dbname=orgsyn

you can't make alkyl iodides from NaI + sulfuric, though it looks like phosphoric would do it. i would think that the chlorides are accessible via HCl + h2so4, but Methyl Chloride is too volatile for swim to work with. also MeI > MeBr > MeCl in terms of methylating ability, right?

OrgSyn doesn't have a specific prep for Methyl Bromide, but they make ethyl bromide in 90-95% yield, one kg produced in a 5L flask.

they warn that alot of EtBr is lost into the atmosphere during distillation.

in the case of methyl bromide perhaps it could be bubbled it into an ice-cold solvent to trap it? its boiling point is 4C so your solvent would have to be quite cold.

this is the only convenient option i can think of for containing the stuff. Windholz says "Methyl bromide is freely soluble in alcohol, chloroform, ether, carbon disulfide, carbon tetrachloride, and benzene."

anyone want to speculate on whether xylene or toluene will work? i think it will. MeBr should be much less volatile when dissolved in a high-boiling solvent cooled below 4C, right?

in US4933498 they use MeCl and MeBr to make 3,4,5-tmba in around 85% yields. perhaps higher. it runs in a stainless steel vessel at 100C under pressure. (they also hydrolyze bromovanillin beforehand in the same pot, it's pretty cool...)

it seems like you could prepare MeBr as an ice cold solution then throw it in the pot, negating the need for a tank of gas. 6 bar pressure could be generated by heating the vessel.

seems quite a bit of work, but somebody has gotta come up with a good OTC mescaline synth eventually...

thanks for all the good info in this thread. so many methylating agents are listed, every one i've heard of... damn good work.

fun with hydroquinone and vanillin.

Vesp, you are talking about 3,4,5-timba from pyrogallol? what is the availability of that? it doesn't seem as common as the other stuff.

poisoninthestain · « **Reply #36 on:** December 26, 2009, 08:47:31 PM »

before Doucher departed we were discussing an OTC, convienient, in situ rxn of MeI between MeOH + KI + NaHSO4...never quite got the time to actually test it myself but thought I'd drop the idea here. We couldn't find any refs unfortunately.

delic · « **Reply #37 on:** December 26, 2009, 09:30:29 PM »

It seems like the sulfate would still get reduced, but what if you used HCl instead: Aqueous HCl, KI and MeOH. Since iodide is a much better nucleophile than chloride, this should allow distillation of MeI (with methanol, and some acid). The chloride shouldn't form, as we don't expect to get methyl chloride from straight methanol + HCl. The distillate might take careful fractionation to get pure MeI, or it could be used straight for methylation if the acid in it is neutralized and the concentration of MeI predicted. One thing I like about this scheme is that it may allow easy iodide recycling, if the salts from the methylation are run again through this reaction to regenerate methyl iodide. That could make the terrible price of MeI more tolerable.

Vesp · « **Reply #38 on:** December 26, 2009, 09:45:11 PM »

I think what they were thinking was forming methyl hydrogen sulfate and sodium sulfate in situation, and then adding KI to produce MeI and HI - which would probably react with

2 NaHSO4 + MeOH => MeHSO4 + Na2SO4*H2O

MeHSO4 + 2KI => MeI + K2SO4 + HI... the HI would react with any excess MeOH, and also an equilibrium would form..

NaHSO4 + KI <==> HI + K2SO4

Right? I don't know... I think reguardless KI + MeOH + NaHSO4 would indeed form MeI, as HI with MeOH does AFAIK and that would form in situation, esp. with the NaHSO4 dissolved in the alcohol...

no1uno · « **Reply #39 on:** December 27, 2009, 10:17:36 AM »

Here's a paper on the use of trimethylphenylammonium (exhaustive methylation of aniline) to O-alkylate phenols, looks quite interesting, especially given that it is the major route to Codeine from Morphine, the end-product is the methylated phenol and dimethylaniline.

If we could work out a way to generate Methyl halides simply and easily, then use them on aniline (for ease of storage & use, plus safety), that I could live with...

Author Topic: Methylating agent sources?? (Read 1306 times)

Sedit

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Vesp

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Sedit

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Sedit

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Douchermann

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Vesp

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Goldmember

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POSEIDON

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Vanadium

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Goldmember

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Formula409

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Baba_McKensey

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Sedit

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no1uno

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madprossor

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madprossor

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poisoninthestain

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delic

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Vesp

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no1uno

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