Sciencemadness Discussion Board

Dimethylsulfate - synthesis

Mephisto - 2-3-2004 at 04:00

I want to know your opinion how it could be possible to improve this synthesis. I have tried a DMS synthesis based on Rhodium's diethyl sulfate synthesis, but get only a very small yield. Here's exactly what I have done:

[color=darkred]500 grams of sodium sulfate were placed in a dry 4 liter flask connected with a condenser and a receiver arranged for vacuum distillation (see below). The flask was heated by means of an oil bath to 150 °C. The apparatus was exhausted as nearly as possible by means of a filter pump, and a mixture of 200 grams of methanol and 590 grams of concentrated sulfuric acid was allowed to drop on the sodium sulfate. The distillation of the mixture required about one hour. The part of the mixture, which didn't distil over at 150 °C remained in the 4 liter flask.
The DMS was separated from the top layer with a separatory funnel. It was washed with a dilute solution of sodium carbonate and then once with cold water, then dried with anhydrous sodium sulfate. Yielding only 30 ml of DMS.[/color]

The set-up:


What did I wrong? I thought the yield would be at least 120 grams. Should I distil at a higher temperature, so that the whole mixture could distil over?

And some information material

Mephisto - 2-3-2004 at 04:01

DDTea - 2-3-2004 at 08:36

I think you might be interested in the section about DMS from War Gases. The method they use is Ullmann's method again, but they have some interesting references:

"Guyot and Simon, employing oleum containing 60% SO3 in the last method [the SO3 being reacted with Methanol] have obtained a very high yield of Dimethyl Sulfate (about 90%)."

However, as you've probably found by your reading, the method preferred to produce DMS is the Chlorosulphonic Acid route.

BromicAcid - 2-3-2004 at 10:51

Do you remember the fuming body incident with Gloria Ramirez? You can do a google search for her name plus DMSO and get some hits if you're interested but the point is, one of the theories for her body possibly producing corpious amounts of poison gas is that she had applied a topical ointment containing large amounts of DMSO to her body, in the ambulance they administered oxygen in excess and the theory states that the DMSO in her body could have added a few oxygens to produce dimethyl sulfate with the excess of oxygen. Could be a possible route to your dimethyl sulfate, even if it isn't it still makes for an interesting read if a little far-fetched.

http://www.gasdetection.com/MDS/m092198.html

http://www.ga.k12.pa.us/curtech/physiolo/Avi/Ramirez.htm

http://home.earthlink.net/~hdcr/Fuming.htm

DDTea - 2-3-2004 at 11:04

That seems like an interesting route... There are a few websites that sell DMSO, and Oxygen is readily available at hardware stores for welding. The temperatures required here are not that high-- just body temperature, and then cooling to allow for the crystallization of DMS. They say nothing of yields, however..

BromicAcid - 2-3-2004 at 11:15

Quote:

Oxygen is readily available at hardware stores for welding


Jeeze, around here oxygen might be readily availible from hardware stores, but it costs $7 for 18g!!!! NO ONE IN THEIR RIGHT MIND PAYS ALMOST $2 A GRAM FOR OXYGEN!! (Yes, I used all caps, I feel strongly on the issue, okay?) But who knows, it might be cheaper where you come from, personally I prefer the catalytic decomposition of H2O2 @ 35% fast and very very cheap.

I however am sceptical of this reaction taking place in the body of a human being at anywhere near an appreciable rate (i.e. I don't think it really happened the way they make it sound) But who knows, it might work on the lab scale, although the oxidation seems a bit off, putting oxygen between the methyl groups and the sulfur and all.

Haggis - 2-3-2004 at 12:03

Dimethyl sulfate...hmm. It's rapidly absorbed into the skin. Once inside the skin, the hydrolysis products are methanol and sulfuric acid. Sounds like a wonderful way to die. You go blind as the methanol is attacking your optic nerve and liver, while the sulfuric acid is scarring your veins, causing inflammation and possibly internal bleeding. Fantastic stuff. As simple as the synthesis is, be careful, this one can bite you back.

Mephisto - 2-3-2004 at 12:25

The 'DMSO to DMS way' is interesting. But I'm only interested in a synthesis with methanol as starting material.

Samosa: I already thought about the synthesis with oleum and methanol from "The War Gases". But I only found an expensive oleum-source. It's possible to make your own oleum this way:

(1) 3 FeSO<sub>4</sub> x aq --[O<sub>2</sub>;<font face="symbol">D</font>]--> FeO + Fe<sub>2</sub>(SO<sub>4</sub>;)<sub>3</sub>

(2) Fe<sub>2</sub>(SO<sub>4</sub>;)<sub>3</sub> --> Fe<sub>2</sub>O<sub>3</sub> + 3 SO<sub>3</sub>

(3) SO<sub>3</sub> + H<sub>2</sub>SO<sub>4</sub> --> oleum

However, for me this is to complicated and time-consuming as for a synthesis of a basic material.

Never thought about the way with chlorosulphonic acid, because this chemical isn't easy to get, too.

Haggis: I know this. I used a ABEK-standard-gasmask and worked in a good ventilated area.

Maybe the yield of my synthesis above could be improved by changing some parameters? What do you think?

Marvin - 2-3-2004 at 12:38

Was the 500g of sodium sulphate anhydrous, it isnt clear from the description or on Rhodium. I think it should be. How much water in the methanol, shouldnt be too much normally, how much is in the sulphuric acid though?

Aside from these I would be worried that the sulphuric will soak up any water vapour in the 'vacuum', if the filter pump is the water type this could be a serious problem. Also to check, the vacuum was isolated during the actual distillation?

I might also be inclined to try less sodium sulphate and drop the mixture in over a longer period, but this is a 'tweak' it wont affect things enough either way.

Ive heard scare stories about how toxic DMS is, I dont plan on using it in future. If I need a methylating agent I might use sodium methyl sulphate. This isnt volatile and sounds easier to make with 'home' concentration sulphuric. Would this work for your application?

Edit in reply to last to posts.

Haggis, nonononononooooo!

Its worse, its a methylating agent which makes it much more toxic than its constituents. Like 20 times, in addition to being carcinogenic and a whole bunch of other things that go hand in hand with methylating agents.

Mephisto, the synthesis doesnt need an 'improved yeild', its failing at somepoint and you need to track down why. Work out what is being done wrong, and get a decent yeild from it. Alternativly, use a different methylating agent for the problem.

[Edited on 2-3-2004 by Marvin]

Polverone - 2-3-2004 at 12:59

I'm just passing on second-hand information here, but recently there was a short discussion about preparing DMS on the Hive itself. Vitus_Verdegast, I believe, suggested that it was better to mix the methanol, H2SO4, and Na2SO4 for some time, then decant the liquid and distill it. The idea was that with that method, any water bound by the Na2SO4 couldn't un-bind when the temperature was raised. I don't know if this modified method had been tested.

DDTea - 2-3-2004 at 16:32

Quote:
Ive heard scare stories about how toxic DMS is, I dont plan on using it in future. If I need a methylating agent I might use sodium methyl sulphate. This isnt volatile and sounds easier to make with 'home' concentration sulphuric. Would this work for your application?


This is of interest, because if you can make Sodium Methyl Sulfate, perhaps you could make Methyl Sulfuric Acid from this...which, on heating, forms Dimethyl Sulfate.

With proper care, DMS is a wonderful Methylating agent, and can act as a cheaper substitute for Methyl Iodide. That's all Samosa has to say on the issue of safety :)

Mephisto - 3-3-2004 at 03:18

Marvin: The sodium sulfate was absolute anhydrous. I dried it 2 hours at 240 °C. The methanol was OTC-bought - I don't know how anhydrous it was. H2SO4 was 96%. I never heard, that the water vapour from the filter pump (yes it was the water type) could get to the distilling-flask. For this it had to pass through both condensers. At 10 mbar it would condense there. The whole apparatus wasn't very well isolated. Therefore the filter pump ran the whole time, to prevent a higher pressure than 10 mbar during the synthesis. So a low air-stream passed through the set-up (from the not airtight fittings to the filter pump). The humidity of this air-stream could be a problem, but I think that's of almost no consequence.
I think the fault was not to distil above 150 °C. There was a big rest of the MeOH,H2SO4,Na2SO4-mixture, which won't distill over at 150 °C. I think the yield would be better if I would distill to 180 °C - even if the part of by-products gets higher.

Polverone: I will check this. Till now I only read half-apint's method for DMS at the hive (which seems to be good, but isn't proved yet).

DDTea - 3-3-2004 at 11:41

Did you try drying your OTC Methanol with a suitable desiccant? Also, you might want to try boiling the H2SO4 until it begins to fume--I'm pretty sure this is important for the reaction.

Mephisto - 3-3-2004 at 15:14

Next time I will dehydrate the methanol with some CaCl2 and boil off the water from the H2SO4. I think the possible 99% methanol from the CaCl2-dehydration will be enough and boiling with some magnesium powder under reflux won't be necessary.

Marvin - 4-3-2004 at 21:18

No dont dehydrate the methanol with CaCl2 they are incompatable.

Commercial methanol should be fairly anhydrous, I'd be more worried about the acid.

SciGuy and Vitus_Verdegast have the idea that dehydration is performed by the sodium sulphate removing the water from the reaction, Verdegast then goes furthur to suggest that dehydration should be done in the cold, followed by decantation and distillation to avoid the heat decomposing the fragile hydrated sodium sulphate. This is presumbly founded in the use of sodium sulphate to dry organic extractions. This doesnt sound right to me as sulphuric acid itself is a much stronger dehydrating agent and what we know doesnt fit his ideas. We can form the monomethyl sulphate in decent yeild mearly by boiling sulphuric acid with methanol (or ethanol) in a 2:1 by weight ratio, letting cool and neutralising. (fownes, but similar to a rhodium synth in the nitroalkane section)

It seems more likley to me the use of the sodium sulphate is in some way related to avoiding the production of diethyl ether or ethene. e.g. sodium methyl sulphate maybe decomposing to dimethyl sulphate and sodium sulphate at heat.

Just when I thought my entire book collection contained only a single paragraph on dimethyl sulphate (telling me how great it is for methylations due to its high boiling point), fownes turns up a prep for methyl hydrogen sulphate (above), similar to the rhodium one, and a surprisingly simple prep for dimethyl sulphate :- 8 to 10 parts of conc sulphuric acid mixed with 1 part of methyl alcohol and distilled neerly to dryness. The layers of the distillate are seperated and the DMS neutralised and dried. The same book also has a method for diethyl sulphate and this is *not* analagous, it involves passing sulphur trioxide into diethyl ether. The reason presumably is that ethyl alcohol will dehydrate to ethene under those conditions (150C or so, sulphuric in excess), whereas methyl alcohol cannot.

I think based on this there are some plausable variations you can try, and be aware that dimethyl sulphate is supposed to decompose at its atmospheric pressure boiling point, the main reason for the vacuum. Fownes is an old reference (middle 19th century) but it does seem reliable. This said its methods are frequently not optimal. SciGuy suggests molar ratios of methanol to acid in his (only!) post on this forum, and also the use of magnesium sulphate, Verdegast on the hive also suggests that trimethyl phosphate can sometimes be used to replace dimethyl sulphate in methylations.

"parts"

Polverone - 4-3-2004 at 21:38

Sorry, a bit unclear: 8 to 10 parts conc. H2SO4 to 1 of methanol means... moles? Grams? CCs? Also, is this an atmospheric pressure distillation in Fownes? And does distilling nearly to dryness mean (as it seems) to distill the majority of the conc. acid as well?!

I like the utter simplicity of this method. If I were to try to come up with a DMS synthesis on my own, I would've said "use methanol and a lot of H2SO4." It's nice to know that intuition can be right once in a while.

Edit: while searching for more information on Fownes, I found a reference to a rather clever preparation of aqueous HCN that he apparently gave: KCN is decomposed with tartaric acid in an alcohol/water mixture; sparingly soluble potassium hydrogen tartrate precipitates and can be easily removed. I think this book may bear ordering, if there are other such interesting bits in it...

[Edited on 3-5-2004 by Polverone]

Mephisto - 5-3-2004 at 05:31

A drying agent is necessary, because water shifts the equilibrium to the left side of the first reaction (lowers the yield).

1) MeOH + H2SO4 <---> MeHSO4 + H2O
2) 2 MeHSO4 <---> Me2SO4 + H2SO4

Mountain_Girl (hive) tried it without dehydration and got a very poor yield.

The claim of Vitus_Verdegast (to dehydrate the MeOH + H2SO4 -mixture and remove the hydrated sodium sulfate) is logically. Above 100 °C it loses it's water again. My main fault was not to remove the Na2SO4 <b>&middot;</b> 10 H20 from the mixture before distilling.

Marvin: I checked it in Roempp (chemistry lexicon): CaCl2 is right for methanol. Other possible desiccants are CaO, magnesium and 3A molecular sieves.

Marvin - 5-3-2004 at 16:26

Polverone,

Parts is usually by weight, particually in 19th century books as I'm sure youve seen before, yes I assume neerly to dryness means most of the acid too. I agree, its a little strange. There is no mention of a vacuum, so I assume a improvement in the yeild is possible when you use lower pressure. The sum of information so far implies that a yeild in excess of 50% is possible with methanol and sulphuric acid alone, based on methanol.

I am unable to find the HCN synth by that method in my copy. The index is shockingly bad, even considering the language. There are also a lot of versions of this book and some may be much better than others. Since the lethal dose for an adult is something like 50mg of HCN, I wont be trying it. It does bring to mind a similar synth where a weak acid is left almost pure in solution by ppting alum though. Some odd ideas and some very clever ones. The plan is to scan the book when I get back to scanning, I only have volume 2 though (organic compounds).

Mephisto,

"Mountain_Girl (hive) tried it without dehydration and got a very poor yield."

Sulphuric acid is a very good dehydrating agent, so I dont share your concerns. What Mountain_Girl tried was a variation at low temperature, high concentration of alcohol and with the DMS voltalised with a stream of gas based on a british patent. Water was also sucked back into the reciver from the trap. From the description it is unsurprising it failed.

I did make a mistake with the sodium sulphate. What can I say, my credibility is completely ruined :D I assumed sulphuric was in excess and it isnt, serves me right for shirking the math. If sulphuric was in excess this would be the stronger dehydrating agent, when not in excess its quite plausable sodium sulphate hydrates. I am under the impression that with methanol the sodium sulphate method is less of an improvement then with ethanol, but it should help. Methanol forms esters more easily (rapidly, completely) than ethanol.

"I checked it in Roempp (chemistry lexicon): CaCl2 is right for methanol."

CaCl2 cannot be used for drying alcohols or amines (including ammonia) becuase it forms adducts, acids (including phenols) and rather oddly esters. This alcohol effect is sometimes used to purify methanol, you form the hex-adduct, evaporate to crystals and decompose the crystals with a large amount of water, followed by distillation and dehydration. Calcium oxide, anhyd. sodium or magnesium sulphate would be fine for drying methanol. The magnesium metal method is the best, but a bit extreme for the circumstances.

There is a lot of information on the hive, some genius, some utter stupidity and a lot inbetween. The method halfapint is using with alcohol,SO2 and CuCl2 is interesting and I partulally like his method for generating SO2 from sulphuric acid and sulphur. The patent that uses sodium pyrosulphate and alcohol alone looks particually promising (USP1506228) for a home synth.

BromicAcid - 5-3-2004 at 20:21

How about a strong, possibly pyro phosphoric acid, that should dehydrate like no-one's business. But it might react under these conditions. Well, anything to drive the equilibrium to the right, eh?

Mephisto - 6-3-2004 at 05:38

Marvin: Excellent work!

I am under the impression that with methanol the sodium sulphate method is less of an improvement then with ethanol, but it should help.

Yes, now I read in Houben-Weyl, that the Na2SO4 improves especially the reaction with ethanol (also NaCl could be used instead of the sulfate).

Fownes' method sounds not very scientific. Without vacuum most of the product would be destroyed. Also distilling to dryness will cause this: At first the dimethyl sulfate comes to the receive-flask, then at higher temperatures the sulfuric acid. Both react back this way:

Me2SO4 + H2SO4 <---> 2 MeHSO4

BTW (Marvin): PM my if you need some help with OCR and PDF-creation from the originals. Some ideas in Fownes could be better than the DMS-method.

Next time I will use some more H2SO4 and Na2SO4 - if I'll use it at all - just in the cold.

thefips - 6-3-2004 at 15:07

Hi @ all! This is my first post.

I think that it is not very difficult to make oleum.
SO3 can be made by heating FeSO4 to ~400°C or mixing conc. H2SO4 with P2O5.
Perhaps 96% H2SO4 could be dried by mixing with Na2SO4 and separating the liquid phase,but I am not sure about this.



[Edited on 6-3-2004 by thefips]

BromicAcid - 6-3-2004 at 19:18

Quote:

Yes, now I read in Houben-Weyl, that the Na2SO4 improves especially the reaction with ethanol (also NaCl could be used instead of the sulfate).


Are you saying to use NaCl in place of Na2SO4 with H2SO4 and MeOH? If that was the case you would probably end up with just HCl considering that H2SO4 reacts with NaCl. If it somehow didn't you would end up with methyl chloride, same as the procedure to make methyl iodide.

Or am I misunderstanding?

Also thefips, your oleum production method is mentioned further up thread.

[Edited on 3/7/2004 by BromicAcid]

Mephisto - 7-3-2004 at 03:26

Are you saying to use NaCl in place of Na2SO4 with H2SO4 and MeOH?

No. I was talking about the analogue reaction, which ends up with Diethylsulfate. This reaction with EtOH is improved by adding Na2SO4 or NaCl. Apparently the synthesis of DMS from MeOH and H2SO4 isn't improved that way.

The DES-synthesis improved by NaCl:
(Note: 2 moles ethyl hydrogensulfate are with 1 mole sodium chloride in one pot.)

C2H5OSO2OH + NaCl → C2H5OSO2ONa + HCl
C2H5OSO2ONa + C2H5OSO2OH → (C2H5)2SO4 + NaHSO4

The reaction could by improved because the ethyl hydrogensulfate would react further with the sulfuric acid (according to Houben-Weyl). Methyl hydrogensulfate doesn't react further this way.

[Edited on 7-3-2004 by Mephisto]

BASF - 14-10-2005 at 11:56

Maybe this patent is useful too..

It describes the formation of sodium methyl sulfate using sodium sulfite, iodine(as an oxidation agent to form SO3 in situ) in aqueous (!) methanol.
The yield seems satisfactory :D

Description of DE4135728

Schwefeltrioxid, das Anhydrid der Schwefelsäure, ist eine seit langem bekannte und für Sulfurierungsreaktionen eingesetzte Verbindung. Es gibt deshalb auch eine Reihe von Verfahren für seine Darstellung, die ausführlich aus anorganischer Sicht in Gmelins Handbuch der anorganischen Chemie 9 (Schwefelband) Teil A, S. 320- 484 und Teil B, S. 323-366 (8. Auflage, 1953), Verlag Chemie, Weinheim, beschrieben sind. Erinnert sei an das Bleikammer- bzw. Kontaktverfahren. Bei beiden wird aus Schwefeldioxid und Sauerstoff im ersten Schritt Schwefeltrioxid hergestellt.

In der organischen Chemie wird Schwefeltrioxid meist als Reagenz eingesetzt, um organische Verbindungen mit beweglichem Wasserstoff wie Alkohole, Phenole, aliphatische und aromatische Amine, aromatische Kohlenwasserstoffe oder auch Heterocyclen zu sulfurieren. Hierbei kann das Schwefeltrioxid je nach Struktur der umgesetzten Substanz und den Reaktionsbedingungen auch an unterschiedlichen Stellen des Moleküls angreifen und eintreten. Bei der Verwendung von Anilin als Modellsubstanz bildet sich bekanntlich mit Schwefeltrioxid erst Phenylsulfaminsäure, die sich bei erhöhter Temperatur in Sulfaminsäure umwandelt.

An Stelle von SO3 können für Sulfurierungen auch Schwefeltrioxidderivate eingesetzt werden wie Schwefelsäure, Chlorsulfonsäure, Chlorsulfonsäureester bzw. Schwefeltrioxid-Addukte an Pyridin, Dioxan oder Dimethylformamid.

Diese Verfahren und Methoden sind z. B. ausführlich beschrieben im Houben-Weyl, Methoden der organischen Chemie, Band 9, S. 343-599 (4. Auflage, 1955) bzw. im Band E11, S. 1042 ff (1985), Georg Thieme Verlag, Stuttgart. Eine eingehende Darstellung findet sich auch in dem Artikel von E.E. Gilbert in Chem. Rev. 62, 549-589 (1962) unter der Überschrift: "The reactions of sulfur trioxide, and its adducts, with organic compounds".

Wie aus den Beschreibungen hervorgeht, sind diese Verfahren nicht universell anwendbar. Es besteht deshalb Interesse an der Entwicklung weiterer, vor allem preiswerter Verfahren.

Wir fanden jetzt überraschend, dass sich Schwefeltrioxid auch in wässrigem Milieu bildet, wenn man Sulfite mit Halogen umsetzt. Wir nehmen folgenden Reaktionsweg an: Überraschend ist dieser Befund deshalb, weil nach bisherigem Lehrbuchwissen bei dieser Reaktion Schwefelsäure bzw. Sulfat entsteht. Diese entstehen nach unseren Untersuchungen jedoch erst in einem 2. Schritt, in dem sich das Schwefeltrioxid mit Wasser umsetzt. Überraschend ist weiter, dass das Schwefeltrioxid unter diesen Bedingungen nicht nur mit Wasser reagiert, sondern auch mit gleichzeitig anwesenden organischen Verbindungen mit beweglichem Wasserstoff. Damit steht ein weiteres Sulfurierverfahren zur Verfügung.

Gegenstand der Erfindung ist ein Verfahren zur Darstellung von Schwefeltrioxid, dadurch gekennzeichnet, dass Sulfite im Beisein von Wasser mit Halogen umgesetzt werden. Ein weiterer Gegenstand der Erfindung ist die Verwendung des hergestellten Schwefeltrioxids für Sulfurierungsreaktionen, dadurch gekennzeichnet, dass die Umsetzung von Sulfit mit Halogen im Beisein von sulfurierbaren Verbindungen durchgeführt wird.

Als Sulfite kommen die Alkali- und Erdalkalisulfite in Frage, aber auch Sulfite, deren Kationen aus protonierten (bzw. quartärnisierten) organischen Basen oder Aminen bestehen. Auch entsprechende Bi- bzw. Disulfite sind einsetzbar.

Bezüglich der Halogene liefern Chlor, Brom und Jod gute Ergebnisse. Die Brauchbarkeit von Fluor ist zweifelhaft. Dafür können Interhalogenverbindungen wie Jodchlorid oder Jodbromid Verwendung finden.

Als besonderer Vorteil der Erfindung wird angesehen, dass als Ausgangsstoffe des erfindungsgemässen Verfahrens Abfallprodukte anderer chemischer Reaktionen eingesetzt werden können, die so einer Entsorgung und zugleich einer Wiederverwendung zugeführt werden. Zu denken ist hierbei z. B. an die Absorption von bei der Verbrennung von Erdöl oder Kohle entstehendem SO2 in Lauge oder Amin und Einsatz des so gebildeten Sulfits in einem erfindungsgemässen Prozess.

Wie in der Einleitung beschrieben, gibt es sehr viele sulfurierbare Verbindungen. Die nachfolgenden Beispiele sollen das Verfahrensprinzip verdeutlichen. Die Anwendungsbreite des Verfahrens lässt sich durch fachmännisches Kombinieren natürlich viel weiter ausschöpfen.


Beispiel 1



Darstellung von Natriummethylsulfat


In 100 ml Wasser wurden 12,6 g Natriumsulfit gelöst. Unter Rühren wurden 100 ml Methanol zugesetzt. Zu der jetzt stark trüben Lösung wurde unter Eiskühlung eine Lösung von 25,4 g Iod in 250 ml Methanol zugetropft. Die Mischung wurde mit etwa 10 ml 32%iger Natronlauge neutralisiert. Die Lösungsmittel wurden am Rotationsverdampfer abgezogen.

Der Rückstand wurde mit 500 ml Aceton verrührt, um das gebildete Natriumiodid zu entfernen. Der verbliebene Rückstand wurde abgesaugt und mit 250 ml Methanol verrührt. Vom unlöslichen Rest (Natriumsulfat) wurde abfiltriert. Das Lösungsmittel des Filtrats wurde verdampft. Es verblieben 8,6 g Natriummethylsulfat=63% d. Th.

Identifizierung durch Vergleich des IR-Spektrums mit dem einer käuflichen Probe.


Beispiel 2



Darstellung von Cyclohexylammoniumcyclohexansulfamat


In einer Mischung von 117 g Cyclohexylamin und 70 g Wasser wurden nacheinander unter Eiskühlung und Rühren 6 g Schwefeldioxid und 5 g Chlor gasförmig eingeleitet. Die Lösungsmittel wurden am Rotationsverdampfer abgezogen. Der Rückstand wurde mit 50 ml Wasser gut verrührt. Anschliessend wurde abgesaugt, mit Aceton gewaschen und getrocknet.
Ausbeute: 17,7 g=677% d. Th.

Das IR-Spektrum der Substanz entsprach dem einer aus äquimolaren Mengen von Cyclohexylamin und Cyclohexansulfaminsäure hergestellten Vergleichssubstanz.

Dimethyl sulphate prep idea and question

mechem - 28-12-2007 at 11:29

Hello everyone

Before I start I must stress DMS is HIGHLY TOXIC and all preparations and use must be carried out in a fume cupboard followed by cleaning all glassware with a methanol/ammonia solution. Remember this substance can affect you hours later so do your research first please.
So far I have not come across any literature on its preparation, but this method might work and I would be delighted to hear about any genuine lab procedure or any quires/ideas you might have with my method. Maybe for example boiling methanol/H2SO4 using a Dean/Stk to remove the water but not heating over 140C. ( DMS decomposes )

I have not tried this yet, but if one mixed equal molar quantities of methanol and conc. H2SO4 in a dropping funnel placed on top of a 3-neck R/B flask set up for vacuum distillation. Then dripped the meth/H2SO4 at a few drops per second into the R/B flask. The R/B flask contains an excess of anhy Na2SO4 preheated to 140 C ( might be a slight problem here with water absorption ). The receiver flask being placed in an ice bath to allow the DMS formed not to hydrolyze back. The DMS can then be washed and separated first with cold sodium carbonate sol. then water and dried over anhy sodium sulphate.


Edit by Chemoleo: Please search before making new threads next time!

[Edited on 28-12-2007 by chemoleo]

Sauron - 28-12-2007 at 15:09

What he means by highly toxic is that DMS is a known human carcinogen and specific brain carcinogen, it causes brain tumors.

Do not mess with it

If you MUST, do so with proper protection IN A FUME HOOD.

peach - 21-9-2011 at 07:07

Old thread, but did anyone make any more progress with it?

It may be of interest that sodium sulphate begins to loose it's water of crystallisation at just 30C, as illustrated in this patent all about cost effectively drying Glauber's salt (sodium sulphate decahydrate) to an anhydrous state for shipping.

And concentrated sulphuric will loose water up to the point of it's azeotrope, passing it over to the receiver for the DMS to land in.

I am listing this section in red to highlight that this is theory rather than fact, regarding a potentially very dangerous process.

If you have them under vacuum, you may shift those points and make it more favourable for water to cause problems.

2 CH3OH + H2SO4 → (CH3)2SO4 + 2 H2O

The easiest way to deal with that, more surely, would be to physically removed the hydrated sulphate once cool and before distillation, as Verdegast suggested.

Despite me constant going on about fridge pumps, the aspirator may actually be of benefit here, as it at least provides for a constant curtain of water over the only exit. A drying tube between it and the apparatus would help prevent vapour back streaming to the product. If using a regular pump, I would want some form of comparable absorption trap before the exhaust made it's way out into the atmosphere.

One solution could be to use water on the low side and ammonia on the high side.
Quote: Originally posted by Sauron  
What he means by highly toxic is that DMS is a known human carcinogen


I certainly would not want to test that! However, it is in the IARC Group 2A, meaning;
Quote:
Substances, mixtures and exposure circumstances in this list have been classified by the IARC as Group 2A: The agent (mixture) is probably carcinogenic to humans.


Here's a copy of the IARC monograph on DMS for those interested.
Quote:
Regulations and guidelines
The American Conference of Governmental Industrial Hygienists (ACGIH) (1997)
has recommended 0.52 mg/m3 as the 8-h time weighted average threshold limit value for occupational exposures to dimethyl sulfate. Values used as standards or guidelines have ranged from 0.05 to 0.50 mg/m3 in other countries (International Labour Office, 1991).
***
Quote:
Studies of Cancer in Humans
As previously summarized, four cases of bronchial carcinoma were reported in men
exposed occupationally to dimethyl sulfate (IARC, 1974). Additional case reports have
since appeared: a case of pulmonary carcinoma in a man exposed for seven years to
‘small amounts’ of dimethyl sulfate but to larger amounts of bis(chloromethyl)ether and
chloromethyl methyl ether (IARC, 1987b), and a case of choroidal melanoma in a man
exposed for six years to dimethyl sulfate (IARC, 1987a).


Quote:
Studies of Cancer in Experimental Animals
Dimethyl sulfate has been tested for carcinogenicity in rats by inhalation, sub-
cutaneous and intravenous injection, and following prenatal exposure. It produced local
sarcomas and tumours of the nervous system (IARC, 1974).


Quote:
Absorption, distribution, metabolism and excretion
As previously summarized, after an intravenous injection of 75 mg/kg bw in the rat,
dimethyl sulfate was no longer detectable in blood after three minutes. No other data were available to the Working Group (IARC, 1974). Dimethyl sulfate rapidly decom-
poses on contact with water to methanol and methyl sulfate (Figure 1) (Mathison et al.,
1995).


Quote:
Human carcinogenicity data
No epidemiological studies were available to the Working Group. A small number of
cases of, mainly, bronchial carcinoma has been reported.


Quote:
Occupational exposure
According to the 1981–83 National Occupational Exposure Survey (NOES, 1997) as
many as 10 000 workers in the United States were potentially exposed to dimethyl sulfate (see General Remarks). No information was available as to the operations in which these exposures might have occurred.


*** To give that some grounds for comparison, I did some digging around for Benzene, which is in the IARC Group 1 (confirmed human carcinogen).
Quote:
In September 2010, the Department of Labour lowered the Workplace Exposure Standard (WES) for benzene.

The old WES for benzene (as of 2002) was:

5ppm or 16mg/m3 TWA (Time Weighted Average)

The new WES for benzene (effective from September 2010) is:

1ppm or 3.19 mg/m3 TWA
2. 5ppm or 7.8 mg/m3 STEL (Short Term Exposure Limit)

What is a Workplace Exposure Standard?

There are, in fact, a number of Workplace Exposure Standards (WES), and they are all designed to give a maximum limit that a person can be exposed to, for a particular substance, over a certain amount of time, and still remain healthy.

In the case of benzene, we use the following values:

Time Weighted Average (TWA) – this means that you could be exposed to an average of up to 1ppm (part per million) benzene over the course of an eight-hour work day and not experience poor health effects.[1]
Short Term Exposure Limit (STEL) –2.5ppm is the highest average level of benzene you can be exposed to over a 15-minute period throughout the working day.


The governments own OSHA site help page for permissible exposures doesn't make mention of whether the TWA has any repetition factored in for; e.g. whether it refers to one day or 30 years of work.

However, DOW does reference the repetition of exposure.
Quote:
Threshold Limit Value (TLV®): Occupational exposure limit set by the American Conference of Governmental Industrial Hygienists. An airborne concentration of a gas or particle to which most workers can be exposed on a daily basis for a working lifetime without adverse effect.¹

Time-weighted average (TWA): A method employed to calculate the exposure of workers to airborne materials, which considers the duration of exposure to various airborne concentrations, usually during an 8-hour day.¹


Lots of quotes in there, but given the high carcinogen risk and lack of a wide experience base, I thought it'd be worth me posting what I've found for anyone else perusing the graveyard.

[Edited on 21-9-2011 by peach]

DJF90 - 31-7-2012 at 14:46

Sorry to bump an old thread but I've come across a complication. US patent 3024263 claims the preparation of ethyl sulfuric acid using the reaction of ethanol with sodium bisulfate. The example refluxes an impossibly small amount of ethanol with sodium bisulfate monohydrate for 4h, but claims a larger volume can be used if required.

I have little interest in ethyl sulfuric acid. My priority lies with finding an appropriate precursor for dimethyl sulfate preparation. To this end I anticipated being able to replace ethanol with methanol in the cited procedure, and expected methylsulfuric acid to form. To this end, 25.06g NaHSO4 (200mmol) (pool grade, anhydrous prills) was added to 81ml of warm stirred methanol (2mol, 5x excess based on the stoichiometry 2NaHSO4 => MeOSO3H + Na2SO4) and the mixture was gently refluxed for 3 hours with appropriate stirring (largest magnetic stir bar that would fit in the conical flask, set at approx 400rpm). Heating was ceased and the mixture was allowed to cool independantly for 40 minutes before application of an ice bath for a further 30 minutes. When removed from the ice bath, a thick slush was observed. This was filtered at the pump, titurated with a little methanol and then the filtrate was concentrated by gentle distillation of the excess methanol over an hour or so (approx 90mls collected). The yellow-tinted fluid was left to cool before attempting a rough density measurement but on my return I was met with crystals (with a little methanol trapped within the solidified structure (see pics).

Now, I'm not sure what's happened here. My first thought is that perhaps sodium methyl sulfate is formed in this instance. However I can't take a melting point due to the trapped methanol, and I'd obviously like to avoid unecessarily playing around with it. I've searched extensively for some resolve, and I've seen breif mention of "sodium methyl sulfate being formed (IIRC "Hexagon" on this site) but I cannot find a reference for that. If it does happen to be sodium methyl sulfate, then it could be that the filtered solids could have also contained some product. I would need to find conditions for the distillation that would yield dimethyl sulfate, something I had hoped to do in the morning (approximately 9 hours from now... So if you can offer help quickly, that would be appreciated very much indeed.

It might be worth mentioning that just prior to concentration of the methanol solution, its pH was tested and gave an orange that changed over the course of a minute or so to red with universal indicator paper. I believe this occurs as the paper picks up water vapour from the atmosphere.

[Edited on 31-7-2012 by DJF90]

DSCF0680.JPG - 166kB

[Edited on 31-7-2012 by DJF90]

Nicodem - 1-8-2012 at 10:55

DJF90, it's been a long time since I read upon alkyl sulfuric acids and don't really remember if methyl sufuric acid can be prepared by the reaction analogous to the US3024263. Though, given that methyl sufuric acid can efficiently be prepared by drying the mixture of H2SO4 : MeOH (1 : 1) with Na2SO4 (as proven by Antoncho in The Hive post #256342), I would expect that the same can be achieved by using anhydrous NaHSO4. Though one needs to consider that a methanolic solution of H2SO4 is already prevalently MeOSO3H even before adding Na2SO4 in regard to the equilibrium (I posted a reference on this topic somewhere), while the NaHSO4+MeOH might not achieve the same equilibrium point in the same time due to the very different acidity.

By the way, are you sure your NaHSO4 is anhydrous? Pool quality bisulfate is usually sold as a monohydrate, at least the one I bought years ago was such.

My only experience with this is pretty much limited. I once left a mixture of Na2S2O7 and methanol stand for a several days, filtered off the salts and rotavaped. This gave a dense colourless liquid - no solids. I know that pyrosulfates are something else, but still, I find it unlikely that you could obtain the sodium salt instead of the acid. Another indication that the equilibrium of MeOSO3H in NaHSO4/MeOH is rather poor, is the miserable yield of methyl iodide obtained in a reaction designed on this hypothetical equilibrium (though there could be other reasons affecting this yield).

Are you sure that the solid is not some NaHSO4 that passed trough the filtration dissolved? This would indicate a failure of the reaction.

In case your reaction just does not want to work, I would suggest a modification that would modify the reaction system to be as similar to the NaHSO4+EtOH reaction as possible. The first such possibility is to reduce the solubility of the bisulfate, for example, by adding toluene as an inert solvent to the methanol. I would use a 4 : 1 or 3 : 1 ratio of MeOH vs. PhMe. Also, let the reaction mixture stand for a day or two before you filter.

PS: In case you are not aware of US1411215, the AlkylOSO3H can efficiently be used directly in the preparation of dialkyl sulfates if anh. Na2SO4 is used as a buffer during the thermolysis. Unfortunately again, the patent only gives diethyl sulfate as the example.

DJF90 - 1-8-2012 at 11:38

Thanks for taking the time to write me a reply Nicodem. I gave up trying to work out what happened (I couldnt get it dry enough to take a melting point although it was like a fine slurry on the hotplate at 150*C) and instead I've just started the addition of sulfuric acid to methanol as per Painkilla's preparation, which references US3047604 and US1411215. I've also taken time to dry my sodium sulfate quickly with a heat gun (I bought anhydrous on ebay a while back but it was packed in a ziplock bag) and ground it finely whilst hot (it was mostly fine anyway so it didnt take long). I should finish the preparation of the methylsulfuric acid this evening, and filter it into the distillation flask (and stopper it) ready for the big distillation tomorrow. I'm running the prep on half the scale of Painkilla, using 1.05 mol methanol and 1 mol sulfuric acid, So I guess theoretical yield is half a mole; 63g (approx 47ml). Assuming a 40% yield like Painkilla, I'll be staring nervously at approx 20ml by tomorrow evening.

Draco_440 - 11-9-2012 at 18:12

Why not follow the method posted here

http://www.sciencemadness.org/talk/viewthread.php?tid=5495

Stop after gas evolution and drip in methanol, reflux then distill

Na2S2O7+2MeOH ---->Na2S04 +(Me)2SO4+H2O

I remember reading a patent for it, I'll see if I can dig it up

SM2 - 12-9-2012 at 05:51

1) Take out a good insurance policy on your self.

AndersHoveland - 15-9-2012 at 13:31

Quote: Originally posted by Haggis  
Dimethyl sulfate...hmm. It's rapidly absorbed into the skin. Once inside the skin, the hydrolysis products are methanol and sulfuric acid. Sounds like a wonderful way to die. You go blind as the methanol is attacking your optic nerve and liver, while the sulfuric acid is scarring your veins, causing inflammation and possibly internal bleeding.

Actually, the reason it is so toxic is because it is an alkylating agent. Cellular DNA gets methylated.