Sciencemadness Discussion Board

Acetic anhydride pondering

12AX7 - 4-5-2007 at 21:53

So, if THF can be oxidized to a lactone (GBL), could it be double-oxidized to a dicarboxylic anhydride (in this case, succinic)? And likewise, by analogy, could diethyl ether's adjecent carbons be oxidized to ketones, giving acetic anhydride? (Neverminding the terminal methyls, which I'm guessing are orders of magnitude more reactive!)

Tim

Sauron - 4-5-2007 at 22:45

I didn't realize there was any shortage of succinic acid.

If you wanted to prepare it in the lab why not chew up butylene glycol (cheap) instead of THF?

Likewise, no shortage of acetic acid, and if there was, always available from ethanol.

So, you aren't really proposing to take THF through GBL to BDO just to turn it into succinic acid?

As to the Et2O you are musing about oxidizing the two methylenes (-ch2-) adjacent to O to carbonyls without disturbing the ehter linkage AND without oxidizing the terminal methyls?

Nice work if you can get it. But I wouldn't recommend quitting your day job.

Do not halogenate as those propducts are nasty vesicants and analogs of sulfur mustard. Carcinogens. Ugh.

Can you reduce Ac2O to Et2O? Not that I ever heard of.

Does the intermediate exist?

Me-CH(OH)-O-CH(OH)-Me? If it did you might have a shot.



[Edited on 5-5-2007 by Sauron]

not_important - 4-5-2007 at 23:10

Yes, the lactone can be taken to succinic acid, although it may take two steps to get there from THF.

The oxidation of ethers generally stops with one methylene being converted to carbonyl, you get esters. Yields are often not that good.

There are much easier ways, and more OTC, to those products than your proposed routes.

Sauron - 4-5-2007 at 23:22

I suspect our colleague was just thinking out loud on the keyboard...

Nicodem - 5-5-2007 at 07:41

Quote:
Originally posted by 12AX7
So, if THF can be oxidized to a lactone (GBL), could it be double-oxidized to a dicarboxylic anhydride (in this case, succinic)? And likewise, by analogy, could diethyl ether's adjecent carbons be oxidized to ketones, giving acetic anhydride? (Neverminding the terminal methyls, which I'm guessing are orders of magnitude more reactive!)

Tim

You can oxidize diethyl ether to ethyl acetate (for example with O2 by a radical process or with several other oxidants). The problem is that the next similar position in ethyl acetate (Me-CH2-O-CO-Me) is much less prone to oxidation that in the original diethyl ether due to the higher electroinductive effect of the acetoxy group when compared to the ethoxy. It would be difficult to oxidize it further under anhydrous conditions (else you don't get the anhydride) and leaving the alpha ester position (Me-CH2-O-CO-Me) intact since it now becomes susceptible to most oxidants (due to enolization, etc.). I don't think there exists any such one step oxidation, but I will check nevertheless.
With THF it is easy to oxidize it to succinic acid which on turn dehydrates easily to succinic acid anhydride by mere heating. However this oxidation is mechanistically different in that the ring of the ester intermediate (GBL) opens and it is actually the alcohol group that gets oxidized (and not the alkyl side of the ester). The analogous reaction on diethyl ether would be its oxidation to acetic acid.

garage chemist - 5-5-2007 at 07:58

THF to succinic acid can be done in one step with high yield, using HNO3 as the oxidiser:
http://www.sciencemadness.org/talk/viewthread.php?tid=7765
I have "discovered" this reaction as you can see. Adding THF to 65% HNO3 gives an immediate reaction producing lots of NOx.
Very similar to the analogous oxidation of cyclohexanol/one to adipic acid.
However, no anhydride is produced.

A milder oxidation method which gives GBL as the main product is outlined here:
http://www.designer-drugs.com/pte/12.162.180.114/dcd/pdf/thf...
See the note about dioxane, which was totally oxidised to CO2 instead of oxalic acid or glycolic acid.

12AX7 - 5-5-2007 at 08:53

Quote:
Originally posted by Sauron
I didn't realize there was any shortage of succinic acid.

If you wanted to prepare it in the lab why not chew up butylene glycol (cheap) instead of THF?


My pondering was in analogy to this reaction, which apparently works. I don't care about succinic anhydride.

Acetic anhydride contains the same group, being an anhydride, and my pondering was purely conceptual (hence "ignoring the methyls", something considerably more difficult in practice than in thought, I would assume).
Quote:
Likewise, no shortage of acetic acid


But there IS a shortage of acetic anhydride made from acetic acid. A lot of people here seem to be concerned about making the stuff, partly because it can't be made from its acid in one step. I'm just thinking out loud (as you say later).

Tim

Sauron - 5-5-2007 at 18:14

Think out loud all you like. However the transformation you are thinking about can't be done. Acetic anhydride can't be prepared from ethyl ether.

We know know how it can be prepared.

Acetic anhydride and oxalyl chloride in one step with proper proportions (Roger Adams, JACS 1920)

Acetic acid and acetyl chloride over tertiary amine (Vogel)

Anhydrous sodium acetate and acetyl chloride (Vogel, Rhodium)

Anhydrous sodium acetate and sulfur and bromine, Russian process (Rhodium from Chem & Ind, 1940s)

All of those are one step. All of those are proven literature routes.

Over the last couple of months we have heard from one member in Iran who says he makes dozens of liters a day by the NaOAc method with Merck acetyl chloride that he buys in 200 L drums for $6/liter.

He wants a cheaper route. I have given him several alternative routes but he has logistical problems, those I can't tackle.

Another member in Pakistan has gone round and round endlessly spinning his wheels trying to implement a couple of the processes I suggested, but he admits he isn't a chemist. And in the case of his least understandable failure it turns out that he was NOT using the reagent I suggested after all (TCT) simply because his supplier delivered cyanuric acid instead of cyanuric chloride, and he never bothered to read the label!

So the question really is NOT how to make acetic anhydride in one step.

Depending on the circumstances of the individual the question might be:

How to obtain or make acetyl chloride

How to obtain or make oxalyl chloride (costlier and more difficult but more versatile)

How to obtain TCT (CC) which is a remedy for the above questions

We have elucidated a number of answers to the first two questions. These include the use of either benzoyl chloride per H.C.Brown's method, or phthaloyl chloride per Kyrides' method, the former is cheap enough, the latter is not but can be readily made and then is just as cheap. (from benzotrichloride and phthalic anhydride). Oxalyl chloride is best made from TCT and oxalic acid.

And one answer to the third question (how to make TCT) which @garage chemist is going to do. Not for the faint of heart.

ALL of the above is apart from the vinyl acetate process which @S.C.Wack suggested and which has yet to be tested in skilled hands. That is acetaldehyde and acetic anhydride as products in one step from VA and acetic acid, with a catalyst.

Further there's a patent suggesting that 1,1,1-trichloroethane can be hydrolyzed under pressure/heat in an autoclave to acetyl chloride, acetic anhydride, or acetic acid, depending on ratio of water. Catalyst required. One step again. However the substrate is now hard to get for many of us and few of us have pressure reactors. So this one is not very practical.

Most if not all of these methods have been documented with articles posted already on this forum in various threads, many of the posts predating my arrival.

Here are a few more that IMO are NOT answers at least for amateur or bench scale:

1. Ketene lamp. Finicky, hazardous and slow. Requires some fancy glassblowing and a really good hood, or a deathwish the size of Gibraltar.

2. The other industrial Ac2) processes.

3. Thionyl chloride. Unsuitable for chlorinating acids <C4. See Vogel. Hard to get. For higher acids OK, and can be made (see Kyrides article on phthaloyl chloride).

4. The phosphorus chlorides. Too hard to get, too hard to make. Some of us are working on this. POCl3 may be tractable.

My intention is not to discourage you from creative speculation but, just trying to clarify the state of the game.

Boomer - 7-5-2007 at 08:13

You mind to tell what those people from iran/pakistan need the Ac2O for?

I'd probably make HMX to bragg about on the internet, but in those countries it is more likely the acetylation of the 3- and 6-position of a certain plant product... ;)

If you had acetyl chloride, would you personally go NaOAc or acid over amine (small scale, just to have done it, no fanzy glassware)?

Sauron - 7-5-2007 at 08:26

The Iranian member says he has a small business making cellulose acetate. This is credible, as the primary use of acetic anhydride in the world is in fact, production of cellulose acetate and after that, vinyl acetate/PVA.

The Pakistani member has never publicly disclosed his purposes, but in the event he is in no great danger of making any AA as he has, frankly, screwed the pooch. So it matters not.

However, it does not really pay to enquire too closely into these issues does it? My attitude is that as long as someone is not blatantly asking for a recipe for a controlled substance, so what? There are a kazillion legitimate uses for acetic anhydride quite apart from either the natural isoquinoline alkaloid you have in mind, or the Bachmann process to cyclic nitramines. I have uses for acetic anhydride that have nothing to do with either and because of where I am I cannot buy it, despite having a legitimate company and routinely buying many chemicals. So I have to make my own. Nothing sinister about it. It's a dehydrated form of fermented grape juice that's gone off. Super vinegar. Not a big deal.

S.C. Wack - 7-5-2007 at 16:00

Quote:
Originally posted by Sauron
Do not halogenate as those propducts are nasty vesicants and analogs of sulfur mustard. Carcinogens. Ugh... Acetic anhydride can't be prepared from ethyl ether.


Yeah well, this is not so much of a desirable route, but I knew of the patent, so...1,1'-dichlorodiethyl ether is part of a patented process for the anhydride, US1859786
and there are two ACS preps for it, one of which is from ether and attached here; though such long chlorination would only be handy if one has a cylinder of it. The other preparation makes use of acetaldehyde:
http://pubs.acs.org/cgi-bin/abstract.cgi/jacsat/1934/56/i09/...

There was an addendum to the vinyl acetate patent BTW, DE526795. The earlier German version of the original US patent on this by the same inventors is referred to there.

Also, the use of other easily made chlorides such as benzyl dichloride and trichloride is also of interest here due to the availability of toluene.

Attachment: joc_15_715_1950.pdf (333kB)
This file has been downloaded 728 times

Sauron - 7-5-2007 at 19:59

Thanks, @S.C., however

1. The page referring to vinyl acetate concerns a reaction in liquid HCl (anhydrous) to produce not Ac2) and acetaldehyde but 1-chloroethyl acetate. Pertinent neither to ethyl ether nor the Ac2O prep.

2. The link to JOC article did not work. It did not open in Adobe Acrobat Professional 8 and instead wanted me to save a file viewthread.php which I cannot open and I DID try both left clicking and right clicking with Save As. I have been using a PC since 1982 and Windows since 3.0 thank you very muc for your advice.

However since the link identifies the JOC file I can go download it
from ACS myself, so thanks for that.

Thanks for the patent and the number of the German addendum to the VA patent.

The second page of the patent pdf from the EPO was corrupt, so I must go and fetch it from freepatentsonline.com or the USPTO server.

If the procedure as described in Example 2 actually works, this is not so bad (75%). Example 1 is clearly impractical and was only included for comparison. I can't examine the other examples till I can obtain second page.

All of those depend on availability on a prep scale of the bis(1-chloroethyl) ether. The other reference you provided suggests chlorination of ether at -20 - -30 C. Not very practicable. The patent claims that chlorination of acetaldehyde with hydrochlorice acid but gives no details or references. The bis(1-chloroethyl)ether is supposed to be sensitive to hydrolysis. Does the inventor mean anhydrous HCl?

Yes that's just what is mean. See following:

"In the same year as Wurz and Frapolli made 1-chloroethyl ethyl ether was bis(1-chloroethyl) ether prepared by Lieben by reacting acetaldehyde with dry HCl gas.[Lieben, 1858]

This reaction was studied further by Geuther et al. [Geuther, 1859] Tishchenko extended the reaction to the preparation of bis(chloromethyl), bis(bromomethyl) and bis(iodomethyl) ether. [Tishchenko,1883]

In 1883 it was shown that acetals in the presence of phosphorus pentachloride would give the corresponding a-monochloro ether.[Geuther, 1883] Later was acetyl chloride[Myolo, 1911] or thionyl chloride[Straus, 1932] used. Acetyl bromide and an acetal gives the corresponding a-bromo ether.[Myolo, 1911]"

The passage above is from:
http://folk.uio.no/toreben/a-monohalo-ethers/Introduction/History/History.html#(5)

References as provided by author Prof.Tore Benneche, Univ. of Oslo

Lieben, A. 1858 Liebigs Ann. Chem.
Geuther, A., Cartmell, R. 1859 Liebigs Ann. Chem.
Geuther, A., Bachmann, A. 1883 Liebigs Ann. Chem.
Mylo, B., 1911, Chem. Ber.
Straus, F,, Heinze, F. 1932 Liebigs Ann. Chem.
Tishchenko, V. 1883, Chem. Ber.


[Edited on 10-5-2007 by Sauron]

enhzflep - 7-5-2007 at 21:09

Sauron,

Don't right click the link then choose save as..

Just left click it then the server will process the viewthread.php file and provide your browser with a link to the desired file.


Oh, and btw - when you write @user_ name, it means (this is directed)at user_name. It is not correct syntax to use it everytime before the name of a user....

Sauron - 7-5-2007 at 23:29

I tried left clicking, and just got a dialog box informing me that the default program (which is Acrobat Professional 8) can't open the file viewthread.php, and do I want to save it?

In short same result as when I try to do a right click/Save As

This not S.C.Wack's fault this is the forum server fucking up AGAIN and before you tell me to install Firefox, last time it did this, last week, it was affecting both IE and Firefox.

I went and got the file from JOC, and I went and got the complete patent from freepatentsonline after the second page of the patent document from EPO's server was corrupted.

Brother @Nicodem found that attachments are being corrupted on forum server if you edit post after attaching file.

not_important - 8-5-2007 at 00:38

Quote:
Originally posted by Sauron
I tried left clicking, and just got a dialog box informing me that the default program (which is Acrobat Professional 8) can't open the file viewthread.php, and do I want to save it?
...
Brother @Nicodem found that attachments are being corrupted on forum server if you edit post after attaching file.


Works for me with Acrobat V7, left click ends up giving a save/open dialog where saving gives the proper filespec.

And I was repeatedly able to download that file of Nicodem's after he had problems trying to DL it, so it's not just editing the post.

Sauron - 8-5-2007 at 00:59

SKIP TO NEXT HEADER IF YOU WANT TOPIC

God damn it, it is a waste of time saying it works for you. It doesn't work for me.

Nicodem's file didn't work for me AND didn't work for Nicodem.

It didn't work for chemrox either.

So obviously SOMETHING is amiss at the forum server level. It is not a matter of good vs bad browser, OS, or color of desktop. It is not a figment of anyone's imagination, it is a real problem. It also ought to be discussed in Forum Matters and not clutter up a thread about chemistry.

BACK TO CHEMISTRY

Apparently this is a fairly well mined subject, as there is a Chem.Rev. article on alpha-haloethers, and here it is:

http://www.4shared.com/dir/2245331/5a78115f/sharing.html

Too big for forum hosting so I put it on 4shared.

I am not altogether enthusiastic about this route as I fear that bis(1-chloroethyl) ether will be of a similar order of carcinogenicity as bis(2-chloroethyl) ether and bis(chloromethyl) ether both of which are well known proven human carcinogens and vesicants analogous to the corresponding S-mustards. That being said this did not prevent the use of the former as an industrial solvent and the latter as a reagent, both now somewhat mutes by OSHA and EPA and CWC. Even so, well, it's an unnecessary hazard as there are alternative routes to Ac2O that do not fuck with one's DNA.


[Edited on 8-5-2007 by Sauron]

S.C. Wack - 8-5-2007 at 04:11

Quote:
Originally posted by Sauron

1. The page referring to vinyl acetate concerns a reaction in liquid HCl (anhydrous) to produce not Ac2) and acetaldehyde but 1-chloroethyl acetate. Pertinent neither to ethyl ether nor the Ac2O prep.

2. The link to JOC article did not work.

The second page of the patent pdf from the EPO was corrupt, so I must go and fetch it from freepatentsonline.com or the USPTO server.


1. ??? I referred to the JACS page as a preparation of 1,1'-dichlorodiethyl ether, which is highly pertinent to the patent. Read it again.

2. The link works fine for me (Pro 6/Firefox/XP), but what I do is click the scroll wheel of the mouse, which opens a new tab and asks me if I want to open, save to... (only because I have it ask every time instead of checking the automatic box) It is not a waste of time telling that there is no problem, when it is obvious from here that there isn't anything "amiss at the forum server level". Alternatively, a single right click and a new window comes up and all is well - but then I configured my mouse for right instead of left and single instead of double, because that's how I like it.

I've had no problems with the second page of either the US or DE patent that I mentioned, neither the first time that I looked at them nor just now.

The references that you're looking for are in the JOC article.

[Edited on 8-5-2007 by S.C. Wack]

enhzflep - 8-5-2007 at 04:25

Sauron, sending the PDF file to your email addr as I type. Enjoy!

-enhzflep

Sauron - 8-5-2007 at 22:39

@S.C., apologies, I indeed missed that little half a line mention of bis(1-chloroethyl)ether in that half a page JACS item.

On the other hand I am inclined to pronounce Requiescat in Pace over this reaction in general.

Liquid neat HCl bp -85 C? How many home chemists have liquid N2 for cooling, or a cryo system to replace it?

If it's beyond the reach of dry ice-acetone (-73 C) it's beyond the capabilities of 99.9% of us.

The alternate is a 15 hr chlorination at -20 to -30 C and a yield of <50% after fractionation.

All the chloroethyl ethers and chloromethyl ethers are proven (as opposed to suspected) human (as opposed to animal) carcinogens so even if the prep were facile it would be to say the least, hazardous if not foolhardy. As I said near the start of this thread. So while the chemistry is interesting a practical route to Ac2O it is not nor is it anything resembling a safe one, it's as bad as ketene if not worse.

But thanks for your help.



-------------------

On the other hand:

Dry ice-acetone temperature would certainly chill a solution of ether, aldehyde or acetal in an inert solvent to well below the -30 range employed by the investigators in the JOC article, and the selectivity of the alpha chlorination ought to increase as temperature decreases. The same may be true of dry HCl; the controlling factor ought to be temperature and not phase. So HCl gas at -60 to - 70 ought to be about as selective as liquid neat HCl below -85.

The bis(1-chloroethyl) ether can be reacted in situ rather than isolated.

So maybe this could be practicable within the bounds of sanity.


[Edited on 10-5-2007 by Sauron]