Sciencemadness Discussion Board

Diethylamine Hydrochloride Synthesis

MrHomeScientist - 1-5-2013 at 07:42

I'm very eager to try the experiment posted by smaerd in the Pretty Pictures thread - making the thermochromic salt bis(diethylammonium) tetrachlorocuprate(II). The only reagent that eludes me is diethylamine hydrochloride, so I am looking into ways of making it myself. Disclaimer: I know very little about organic chemistry!

There already exists a thread on making diethylamine, and I read this with the thought of making that compound then reacting with muriatic acid to precipitate the acid salt. However there was one method mentioned to directly make it using acid hydrolysis instead of base hydrolysis - here's an excerpt from page 4 of that thread:

Quote: Originally posted by Arrhenius  
Acid Hydrolysis (already suggested by Ritter):

I.) Reflux a solution of ~ 3:1 (v:v) DEET:HCl (30% muriatic acid is probably okay) for ~1-2hr.
II.) Cool the solution to room temperature.
III.) Extract the resulting solution with toluene (easy to get) to remove the (similar to toluene) m-methylbenzoic acid.
IV.) Boil off the water/acid in a fume hood or outdoors to yield Et2NH*HCl.
IIV.) For fun, let the toluene evaporate and hopefully you'll find your m-methylbenzoic acid left behind.

*Note: I don't believe there's anything particularly dangerous with this procedure. As always, a hot plate is preferred over a bunsen burner, toluene is flammable (DEET too), and if you get acid on yourself wash it with water immediately. HCl vapor is not particularly dangerous as it is too irritating to stay near for more than a couple seconds. Oh.. and don't eat any of your products.


My question is, does this sound feasible? Has anyone tried this? There was little talk about it in the rest of the thread. There were numerous mentions of needing a cosolvent like ethylene glycol for the base hydrolysis, but I'm not sure if it's necessary here. Again, I don't know much about organic. I was able to purchase 98.11% DEET, and I have a small amount of toluene (can anything else be used in its place? I'd prefer using something I have more of).

I'd have posted a reply in the existing thread, but I am more interested in the hydrochloride salt than diethylamine itself.

blogfast25 - 1-5-2013 at 09:35

This would be better suited to the organics section.

MrHomeScientist - 1-5-2013 at 11:50

I suppose; if a mod would like to move this please do so. I just had worried my lack of references would be offputting to some over there (plus organic is a big and scary place for someone as inexperienced in it as I!).

DrSchnufflez - 1-5-2013 at 15:17

I have also been looking into a route to make diethylamine hydrochloride so that I can synthesize the tetrachlorocuprate complex.
So far I have the following steps:

Cleave DEET to form diethylamine and the sodium salt of meta Toluic acid via the procedure suggested by Jon in the diethylamine thread

Quote: Originally posted by jon  
i got this from a chemist who made it from deet

OTC Hydrolysis of N,N-diethyl-meta-toluamide (DEET) to Diethylamine and M-toluic acid


To a 250ml autoclavable media bottle is added in order, 175ml N,N-diethyl-meta-toluamide (98.11% comerc grade, $15) followed by 40ml 70% EtOH. the media bottle is capped and vigorusly shaken for one minute. the EtOH and DEET should now be a homogenous mixture. to this solution is added 40g NaOH and once again capped. the media bottle containing the mix is now sealed and heated in a hot water bath (crock pot set on low) added to the bath at 55*C (125*F) ending at 70*C (160*F) periodicly agitating for the legnth of time it takes to compleatly desolve the NaOH plus 1.5hr. the solution should now be a deep yellow color the crock pot is turned off and allowed to cool to RT. it is removed from the bath and allowed to stand at RT for one day minimum. the bottle will then be carefuly opened after cooling in the refridgerator for 1hr. obsedved was the strong smell of diethylamine, no longer did it smell of DEET and EtOH. the solution is fractionaly distilled (dont forget boiling chips, this stuff likes to bump) collecting the fraction along a 9 degree tempeture arc centered on 55*C (51-59*C). the solution may solidify twords the end of the distilation and a small ammount of DH2O can be added to liquify the waxy mass of M-toluic acid and NaOH. total yeild form aprx 225ml of solution was 57ml of crystal clear diethylamine in freebase form. 25.3%

MeOH can be used in a pinch but i like EtOH, it mixes better with the DEET and has just enough water for the hydrolysis but not enough to cause separation.

Diethylamine C4H11N 73.14g/mol boiling point 55.5*C (131.9*F)

N,N-Diethyl-M-Toluamide C12H17NO 191.27g/mol boiling point 288-292*C (550.4-557.6*F)

M-toluic acid C8H8O2 136.15g/mol boiling point 263*C (505.4*F) (melt at 111-113*F)
-------------------------------------------------------------------------------------------------------------------------------------
Ethanol C2H6O 46.07g/mol boiling point 78.4*C (173.12*F)

Methanol CH4O 32.04g/mol boiling point 64.7*C (148.4*F)

water H2O 18.015g/mol boiling point 100*C (212*F)




Then reflux the Diethylamine with either aqueous or ethanoic hydrogen chloride to synthesize diethylamine hydrochloride

I am farly new to organic chemistry so I am not sure weather the conversion to diethylamine hydrochloride will work though.

DrSchnufflez

aaparatuss - 1-5-2013 at 20:06

Well if you ever get around to isolating the tetrachlorocuprate its a beautiful but hygroscopic compound.

The reaction conditions to make it need to be anhydrous as well.


Then when you have the best dry crystals you can achieve i would try to encapsulate the crystals between to microscope slides some how sealed.

This way you will have tiles that you can play with.

Also be careful with over heating them as you will quickly destroy them.


You will probably come to the realization that the best way to control them is a peltier device.

Then you will have tiles each controlled by a peltier device ... then of course you could form a large grid and control the color change with a computer program. Ether heating or cooling for the maximum wow factor...

Go further then i did my friend....


Cheers....







MrHomeScientist - 2-5-2013 at 05:45

Quote: Originally posted by DrSchnufflez  
I have also been looking into a route to make diethylamine hydrochloride so that I can synthesize the tetrachlorocuprate complex.
So far I have the following steps:

Cleave DEET to form diethylamine and the sodium salt of meta Toluic acid via the procedure suggested by Jon in the diethylamine thread

[snip]

Then reflux the Diethylamine with either aqueous or ethanoic hydrogen chloride to synthesize diethylamine hydrochloride

I am farly new to organic chemistry so I am not sure weather the conversion to diethylamine hydrochloride will work though.

DrSchnufflez


That was my initial thought as well (and I actually found that procedure where it was originally posted on Zoklet.net before I saw it on SM), but the mention of directly making it by refluxing with acid instead of base sounded simpler to me. Plus I don't have a fractionating column so isolating the product would be difficult, I think. I was hoping someone could comment on the validity of the acid hydrolysis method.

If no one has tried it, I suppose I should soldier on and experiment myself. I just don't know how to test the products I obtain, really.


Quote: Originally posted by aaparatuss  
Well if you ever get around to isolating the tetrachlorocuprate its a beautiful but hygroscopic compound.

The reaction conditions to make it need to be anhydrous as well.

Then when you have the best dry crystals you can achieve i would try to encapsulate the crystals between to microscope slides some how sealed.

This way you will have tiles that you can play with.

Also be careful with over heating them as you will quickly destroy them.

You will probably come to the realization that the best way to control them is a peltier device.

Then you will have tiles each controlled by a peltier device ... then of course you could form a large grid and control the color change with a computer program. Ether heating or cooling for the maximum wow factor...

Go further then i did my friend....

Cheers....


Neat ideas! I especially like the peltier element for more controllable temperatures. My idea for presentation was to sandwich the crystals between two watch glasses or petri dishes so I can hold it vertically, and heat it from behind with a heat gun. We'll see how that pans out.

Also you mention overheating can destroy them - are you sure? What temperature does this happen at? The papers that smaerd kindly provided me in the References section say that you can heat them until they melt with no decomposition. If they do melt, they have an interesting tendency to supercool in the yellow state, and only slowly switch back to green.

DraconicAcid - 2-5-2013 at 11:38

Quote: Originally posted by DrSchnufflez  

Then reflux the Diethylamine with either aqueous or ethanoic hydrogen chloride to synthesize diethylamine hydrochloride

I am farly new to organic chemistry so I am not sure weather the conversion to diethylamine hydrochloride will work though.

DrSchnufflez


Once you've got the diethylamine, you won't have to reflux it with acid to get it to convert- just add the acid. Acid-base reactions are faster than most reactions.

MrHomeScientist - 7-5-2013 at 06:29

My thread was moved here at my request (thanks woelen!), to see if anyone 'round these parts might have more input. I'm interested in the direct synthesis of the hydrochloride, so I don't have to go through the distillation step. I don't have a fractionating column, so I'm concerned about my ability to accurately collect a product over a narrow temperature range.

Diethylamine Hydrochloride Disposal

MrHomeScientist - 30-11-2015 at 13:47

I ended up purchasing some of the title compound to attempt the thermochromic crystal synthesis, and long story short I could never get it to work properly. So, I have a small amount (<25mL) of diethylamine hydrochloride in anhydrous ethanol to dispose of. Anyone know of any simple reactions to render this chemical into a less harmless, safe to dispose down the drain form? I have access to many standard inorganic laboratory chemicals (acids, bases, hydrogen peroxide, etc.), but not very many other organic reagents.

[Edited on 11-30-2015 by MrHomeScientist]

aga - 30-11-2015 at 14:02

I admire your persistence MrHomeScientist, truly.

How about we call in the Big Guns and try to work this out ?

Chances are that NaOH will wreck it up enough to render it 'disposable' although i am nowhere near an expert.

[Edited on 30-11-2015 by aga]

softbeard - 30-11-2015 at 14:09

As far as I am aware, diethylamine has a low order of toxicity, on par with ammonia. An ethanol solution of the hydrochloride salt is relatively innocuous, especially if it is a small quantity.
I would just dilute your diethylamine.HCl/ethanol solution with 10 x its volume of water and pour it down the drain or let it soak into the ground.

careysub - 30-11-2015 at 14:16

If it is in usable condition someone might like to take that off your hands.

MrHomeScientist - 1-12-2015 at 13:21

Unfortunately it was purchased for my outreach program with Not My Money<sup>TM</sup>, so giving it away is unfortunately not an option.

My MSDS does list it with 1's across the board, so it certainly doesn't seem too dangerous. Just seeing if anyone knew of a way to destroy the compound in case drain disposal wasn't a good idea.

clearly_not_atara - 1-12-2015 at 15:29

NaOH will do nothing. Whatever you do, don't sell it: it's a List I chemical as an essential LSD precursor and you'll be riding the partyvan faster than you can say "phosphorus oxychloride".

Simple answer is to set fire to it, outside of course, as long as it contains no Cl or P you'll be fine.

JJay - 1-12-2015 at 15:35

It's perfectly legal to possess phosphorus oxychloride, right?

clearly_not_atara - 1-12-2015 at 16:13

Yes. Also apparently it's monoethylamine that's listed, not diethylamine. Diethylamine is watched, but not listed. I guess ethylamine is a solvent for Birch reductions (shake n' bake meth). Still, I would not fuck with that.

[Edited on 2-12-2015 by clearly_not_atara]

zed - 1-12-2015 at 17:03

Hmmm. Perhaps, the list has changed.

Seems like I remember Diethylamine as being listed.

There are also , remember, other lists. Those pertaining to potential chemical weapons, and other WMD.

If you wish to purchase a trainload of PCl3, the rules are different. Some enthusiastic company will find a way to fill your order, regardless of regulations. Money talks.



[Edited on 2-12-2015 by zed]

[Edited on 2-12-2015 by zed]

careysub - 1-12-2015 at 20:23

Diethylamine, and its salts are on the DEA "Special Surveillance List Published Pursuant to Title 21, United States Code, Section 842(a)(11)".

So are sodium metal, magnesium metal turnings, sodium and potassium dichromate, formic acid, Freon-11 and Freon-113.

MrHomeScientist - 2-12-2015 at 07:14

Let's not all panic here. This chemical was bought from Alfa with government money for a government outreach program. I'll be fine.

careysub - 2-12-2015 at 07:55

I have been curious about this DEA listing thing for some time, and pay close to attention to what is on their lists, but for their regular list II (not "special surveillance") includes things like: acetone, potassium and sodium permanganate, MEK, toluene, hydrochloric acid, sulfuric acid, and MIBK -- all of which can be purchased OTC for various uses (mostly from standard hardware stores).

Knowing that these common chemicals appear on a "DEA list" is what motivates me to try to understand what is really a likely cause of harassment by law enforcement.

If you look at the reporting quantities of the things I listed above the amounts are very large: 50 gallons (*per month*) of toluene and acetone for example.

Clearly they aren't tracking these List II chemicals like they are some List I chemicals like white phosphorus or pseudoephedrine.

For the "special surveillance list", which diethylamine appears on, the corresponding regulation appears to be simply the admonition (in its entirety):

"The Comprehensive Methamphetamine Control Act of 1996 (MCA) makes it unlawful for any person to distribute a laboratory supply to a person who uses, or attempts to use, that laboratory supply to manufacture a controlled substance or a listed chemical, with reckless disregard for the illegal uses to which such laboratory supply will be put. Individuals who violate this provision are subject to a civil penalty
of not more than $25,000; businesses which violate this provision are subject to a civil penalty of not more than $250,000. The term "laboratory supply" is defined as "a listed chemical or any chemical, substance, or item on a special surveillance list published by the Attorney General, which contains chemicals, products, materials, or equipment used in the manufacture of controlled substances and scheduled listed
chemicals."

This is in a 76 page handling manual, providing guidance to people actually selling this stuff on what to do.

It appears then that the "special surveillance list", which includes diethylamine, has no reporting requirements, and is not actually being tracked at all in an active sense. I would come into play (I gather) when an operation gets busted, and criminal charges are being prepared (i.e. seller beware).

So far I have not seen any clear account on this site about someone being visited by the law for a small purchase of a List II or "special surveillance" chemical.

http://www.deadiversion.usdoj.gov/pubs/manuals/chem/chem_man...

Bezaleel - 2-12-2015 at 08:10

Quote: Originally posted by MrHomeScientist  
I ended up purchasing some of the title compound to attempt the thermochromic crystal synthesis, and long story short I could never get it to work properly. So, I have a small amount (<25mL) of diethylamine hydrochloride in anhydrous ethanol to dispose of. Anyone know of any simple reactions to render this chemical into a less harmless, safe to dispose down the drain form? I have access to many standard inorganic laboratory chemicals (acids, bases, hydrogen peroxide, etc.), but not very many other organic reagents.

[Edited on 11-30-2015 by MrHomeScientist]

I'd be interested in your long story long ;)
Seriously, what exactly did you try?

Offtopic: A while ago I tried to synthesize Ni(en)2(PbI3)2, but without any success. This left me puzzling, as the publication simply calls for a strong solution of Pb(OAc)2 in KI solution (1:4 ratio - top of my head) and dripping into this Ni(OAc)2 with (en) (1:1 ratio) dissolved in 50ml of H2O.
Nothing happened, just the green nickel solution on top of the PbI2 that had remained largely undissolved.
I'm trying to dry this in a desiccator, but to no avail, as a thin layer of PbI2 forms on the surface, preventing further evaporation of the solvent.

MrHomeScientist - 2-12-2015 at 08:46

Apparently I've already posted my experimental details: http://www.sciencemadness.org/talk/viewthread.php?tid=30117

I came across that while looking up the paper I based the experiment on, so lucky for me I didn't have to type it all again :P

Bezaleel - 4-12-2015 at 08:40

Thanks, going to read through it right away :cool:

skip - 4-12-2015 at 16:01

Right stupid to buy some diethylamine hcl and toss it out, fuckin dumb. I swear some people have no buisenss tinkering with chemicals.

zed - 2-1-2016 at 15:56

Eh....No big deal. Easy to make. Lots of ways to make it.

Some of the guys seem to have no problem, just buying it by the liter.

Dr.Bob - 2-1-2016 at 19:47

If you have Et2NH HCl in ethanol, just let the ethanol evaporate, and you will get a solid which is safe to store and dispose of.

And to make it, using 6N HCl and DEET for about 6-12 hours at 100 C should cleave the amide to the amine HCl salt.

careysub - 2-1-2016 at 21:38

Quote: Originally posted by Dr.Bob  

And to make it, using 6N HCl and DEET for about 6-12 hours at 100 C should cleave the amide to the amine HCl salt.


Are you speaking from actual experience?

One thing I noted on the very lengthy DEET thread(s) was an apparent lack of SM members confirming a successful procedure.

clearly_not_atara - 3-1-2016 at 00:58

I've seen a couple reports claiming success with DEET but not on SM. What successful reports have in common is that they're done in small batches using alkaline hydrolysis with excess NaOH or KOH and the NHEt2 is distilled right out of the rxn mixture.

No idea about acidic hydrolysis. It sounds difficult. I would try using a PTC with the acidic hydrolysis, and maybe a water/acetone solvent mixture or water/DMSO if you have it.

I've heard some salts, notably copper nitrate, can catalyze amide hydrolysis. I don't know how well it will work with this substrate.

[Edited on 3-1-2016 by clearly_not_atara]

byko3y - 3-1-2016 at 09:27

Tell me more about acidic PTC catalyst. AFAIK for most cases tosylic or trifluoroacetic acid plays the role of catalyst.

nlegaux - 3-1-2016 at 15:46

I was able to successfully prepare freebase diethylamine with the following procedure. I refluxed 50ml DEET with 32ml 8M HCl(aq) for 1.5h. Following this, I added 15g NaOH (which was first dissolved in 20ml water) and distilled off the resulting diethylamine with a 75% yield. It may be easier to purify the freebase in this way and form the salt afterwards than attempt to purify the salt from the m-toluic acid produced.

nlegaux


[Edited on 1-3-2016 by nlegaux]

JJay - 13-8-2017 at 20:17

I'm giving this a try with 5 mL DEET and 4.4 mL azeotropic HCl.

JJay - 13-8-2017 at 23:53

After refluxing gently for about three hours and seeing little change aside from a light pink color forming, I turned up the heat to establish a rolling boil. This quickly resulted in the formation of a light precipitate, likely m-toluic acid. Fortunately, the increased reflux didn't threaten to flood the air condenser that had been placed over the flask. I'm going to let it run for a while longer and then add some base and distill the DEA!



JJay - 14-8-2017 at 09:21

I ended up adding 2 mL more azeotropic HCl and running for about five hours, with two hours at a rolling boil. I definitely got some product (smells like ammonia), but there's a lot of DEET still left, and however much product there is, it's not enough to distill through a microscale column in a boiling water bath. I'm doing a simple distillation right now, but I don't expect much (maybe a mL if I'm really lucky, probably more like 0.1 mL), and it will probably have some water in it. I'm actually headed out of town, but when I get back I want to try with sulfuric acid.

Edit: Oh and I should mention that I added 2.2 grams of NaOH in 5 mL water before trying to distill it, and I basically only got enough diethylamine to wet the inside of the still head, although it does have a strong ammonia odor.

[Edited on 14-8-2017 by JJay]

sykronizer - 17-12-2017 at 04:09

If you are desperate or out of reagents there is a simple source of dimethyl, diethyl and isopropyl amine....it's in your hardware store, or garden store etc. The weed killers (bare with me!) the ones that contain only Glyphosate, and there are plenty of them, are made water soluble by creating an amine salt...that's right...so, all you need to do is get the stuff that's around 36 percent Glyphosate and chill it, add some non polar solvent, then some concentrated sodium hydroxide, mix thoroughly and the amine will become freebase and dissolve into your organic solvent which will separate out in minutes. Different brands use different amines, but I have seen at least these three.

DJF90 - 17-12-2017 at 15:23

Quote: Originally posted by JJay  
I'm doing a simple distillation right now, but I don't expect much (maybe a mL if I'm really lucky, probably more like 0.1 mL)
...I basically only got enough diethylamine to wet the inside of the still head, although it does have a strong ammonia odor.

[Edited on 14-8-2017 by JJay]


You know the boiling point of dimethylamine is 7 *C, right?

JJay - 17-12-2017 at 15:52

I wasn't really expecting any dimethylamine... I'd expect most diethylamine to be condensed by an air condenser, though. I think a better workup is likely to heat more strongly, neutralize the distillate with clean hydrochloric acid, and boil off the water. The diethylamine hydrochloride could be heated with sodium hydroxide and the vapors condensed and dried to obtain pure anhydrous diethylamine (I think).

I've been meaning to try it again with 60% sulfuric acid on a larger scale.

DJF90 - 17-12-2017 at 16:07

Apologies, I clearly misread the target wrong.

In any case, you might be better off running the hydrolysis (monitor for consumption of DEET by TLC), and then filter (?) or extract the acid with organic solvent. Concentate the aqueus to yield Et2NH*HCl, recrystallise for purity, and then proceed to the salt release.

JJay - 17-12-2017 at 17:02

That seems reasonable.

clearly_not_atara - 17-12-2017 at 17:58

Quote:
I ended up adding 2 mL more azeotropic HCl and running for about five hours, with two hours at a rolling boil. I definitely got some product (smells like ammonia), but there's a lot of DEET still left, and however much product there is, it's not enough to distill through a microscale column in a boiling water bath. I'm doing a simple distillation right now, but I don't expect much (maybe a mL if I'm really lucky, probably more like 0.1 mL), and it will probably have some water in it. I'm actually headed out of town, but when I get back I want to try with sulfuric acid.
I think you probably want to add more water. Azeotropic HCl should have a pretty strong affinity for water (hence its bp above that of pure water) but 1 M HCl is only 0.6 pH points less acidic than 6 M (azeotropic) HCl. I think about this in terms of the chemical potential of the H2O molecule:

http://en.wikipedia.org/wiki/Chemical_potential

The chemical potential of water roughly defined is the "energy released" when you add one molecule of H2O to the solution through cohesive forces. By conservation of energy, it's the energy cost of hydrolysis. In concentrated acids, the chemical potential of water is large -- the solution heats up when you add water -- so the reaction (R2NH + RCOOH <<=>> H2O + RCONR2) shifts to the right. In dilute acids, the chemical potential of water is less, so the reaction shifts left. You also see this effect in sulfonation reactions, where dilute acid promotes desulfonation and concentrated acid promotes sulfonation. So with 1 M HCl, the reaction should shift to the left and produce more diethylamine.

Fun fact: Azeotropic HCl is HCl*8H2O almost exactly.

[Edited on 18-12-2017 by clearly_not_atara]

JJay - 17-12-2017 at 18:08

Quote: Originally posted by clearly_not_atara  

I think you probably want to add more water.


Hmm... interesting idea... DEET is only slightly soluble in water....

clearly_not_atara - 17-12-2017 at 22:36

That will slow the reaction down, for sure, but most solubility numbers for deet in water that I see are at room temperature. At reflux it should be high enough to achieve a decent rxn rate I'd expect.

gravityzero - 26-1-2018 at 17:59

This seems like a fairly cheap and easy procedure to attempt. It is odd that no one has reported much success.

The procedure originally reported by Jon appears to be worth a try.
My only concern is it appears to be a sort of "pipe bomb" method.
Is the procedure describing heating a closed system in an autoclave bottle?
Seems dangerous to me. Am I misreading this method?

Another method describes refluxing ethylene glycol, NaOH, and DEET.
I assume a stoppered reflux column with a tube leading to cold water? or maybe ethanol? Where the diethylamine gas is collected.

Pumukli - 30-1-2018 at 06:25

Quote: Originally posted by sykronizer  
If you are desperate or out of reagents there is a simple source of dimethyl, diethyl and isopropyl amine....it's in your hardware store, or garden store etc. The weed killers (bare with me!) the ones that contain only Glyphosate...


Diethylamine is not used afaik in herbicides. I have seen dimethylamine and isopropylamine and even potassium salts of glyphosate (and the former two amine salts of 2,4-D, and MCPA).
So you can't get diethylamine from these often handy sources.

Mush - 31-1-2018 at 16:47

I lost most of my notes (among this synthesis), unfortunately. This is all I remember.

4,062 g repellent (assy 98% deet) was refluxed with NaOH/ EtOH (denaturated EtOH was distilled once) for about 4 hours. Not much change was noticed in the first hours. At 3-4 hour characteristic amine odor started escaping through the condenser. Reaction was stopped at the end of 4th hour . HCl was added to the mixture after it until PH 6.Thick white smoke (ph paper turned blue upon test) developed during hcl addition . The reaction mixture was filtered then evaporated to dryness. Snow white, soft crystals were scraped off and dissolved in minimum amount of EtOH. Insoluble residue was filtered off (NaCl). Thus obtained filtrate was evaporated to dryness, yield: 0,068 g HCl salt.

Qualitative test:
~0,010g of the above hcl salt was dissolved in ~1 ml ion changed water,a few drops of strong NaOH solution was added. Strong amine odor was detected. Ph paper turned blue holding it close to the mouth of the test tube. Test: +


Conclusion:
This reaction does work at atm pressure, however it has its limitations.


[Edited on 1-2-2018 by Mush]

clearly_not_atara - 1-2-2018 at 12:00

See the attached review on amide hydrolysis. Choice quotes:

"B. Occurence of a Rate Maximum -- Since the acid-catalyzed hydrolysis of amides is reasonably slow, reactions may be carried out in quite high acid concentrations, and as the acid concentration is increased the rate increases to a maximum and then decreases."

"B. Substituent Effects -- Reid investigated the effect of nuclear substituents on the rate of hydrolysis of benzamide and observed that meta- and para- substituents such as -NH2, -OMe, and -Me retarded the rate, whilst -I, -Br, and -NO2 increased it."

"C. Catalysts -- [...] Cationic acids of the amine type, e.g. monoethanolamine, which cannot both donate and accept a proton in a concerted mechanism and are therefore supposed to act only as general acids, can be very effective."

I think that based on Mush's report some of his diethylamine escaped because its bp is lower than ethanol and some of it was never formed because he stopped the reaction shortly after he first smelled it. It might have taken days at that rate, though.

Perhaps nitrating DEET deserves more attention. The product might undergo alkaline hydrolysis at a lower temperature, preferably below the boiling point of diethylamine. I also think that performing acid hydrolysis with a cosolvent would be a good idea.

Attachment: oconnor1970.pdf (805kB)
This file has been downloaded 160 times

[Edited on 1-2-2018 by clearly_not_atara]

Boffis - 28-9-2019 at 06:06

I have just tried the acid hydrolysis of DEET. I used 6.9g of crude m-toluyl-N,N-diethylamide extracted from bug repellant by dilution with water and allowing the liquid to separate into two phases. The organic phase was not dried. The crude DEET was mixed with 20ml of 70% sulphuric acid and heated to 180 C for 2 hours by which time the reaction mixture resembled crude oil! I cooled the mixture and diluted it with 50ml of water and neutralised it with 50% NaOH, reheated it with the addition of 2g of charcoal and 1g of cellite filter aid, filter it hot and cooled. The filtrate was now pale straw coloured to my amazement but did not smell fishy. Rendering a small sub-sample (c 5ml) strongly alkaline with 50% NaOH also fail to generate much evidence of diethylamine though the vapour did slowly blue moist litmus paper.

The remaining filtrate contained a few drops of brown oil so I tried to extract this with ether but the whole lot rapidly solidified into a mass of colourless crystals, these were filtered off and found to be sodium sulphate. The filtrate was allowed to stand in a small separating funnel, the aqueous phase run into a beaker and acidified with 36% HCl. The mixture became cloudy and a little oil separated but no m-toluoic acid crystallised out.

Conclusion. Sulphuric acid hydrolysis does not look like a practical method.

[Edited on 28-9-2019 by Boffis]

Tsjerk - 28-9-2019 at 07:05

I would use a lot less concentrated acid (HCl, so you have less hygroscopic stuff during drying). I think acid hydrolysis is the way to go as while protonated diethylamine won't be lost as a gas.

As a workup I would extract the m-toluic acid with for example toluene from the crude reaction mixture, neutralize to pH 7 with NaOH and boil down the aqueous layer to get the dry salts* and extract the amine.HCl salt with methanol. Evaporate the methanol.

*If you have toluene anyway you can use it to dry the salt mixture after getting rid of most of the water.

[Edited on 28-9-2019 by Tsjerk]

Pumukli - 28-9-2019 at 08:34

Thanks Boffis for the experiment! I'm amazed that 2 hours at 180 C in 70% H2SO4 was not enough! You saved me a failure and some wasted reagents because if I had tried this reaction I'd have done roughly the same.

The question is: how to proceed?

Boffis - 28-9-2019 at 10:27

Well I also did a test-tube scale test with KOH solution and enough alcohol to give a homogeneous solution and refluxed it for 2 hour with not even the faintest hint of fishy smell so for my next trick I will try more aggresive conditions. I am going try a modification of Dr.Bob's glycol method and catch the amine in dilute HCl.

@Tsjerk: If 70% H2SO4 produces vertually no hydrolysis after 2 hours why should 36% HCl do better? After all the first proton of sulphuric acid is about as ionised as HCl so there isn't really much difference in H+ ion concentration. The only difference is that carbonisation may be less with HCl so a much longer reflux can be used. I don't think you would need to extract the m-toluic acid, I think that it is sufficiently insoluble even in strong HCl to simply precipitate on cooling and can then be filtered off on a glass frit. Recovery of the amine would be best by neutralisation and distillation into fresh HCl and then evaporate this to dryness to remove the excess HCl.

I may try an HCl hydrolysis with a long reflux if the mixture doesn't blacken.

Pumukli - 28-9-2019 at 12:01

Refluxing with HCl may be trickier. The 20% azeotrope boils around 110 C... 36%? Wouldn't it loose too much HCl with time in an open system? 180 C vs. much lower temp that can be achieved with HCl with roughly the same H+ concentration. I doubt it would be much better.

Or maybe this one:
https://quod.lib.umich.edu/a/ark/5550190.p009.205/1

(Dioxane solvent, NaOH in MeOH, reflux at 80 C, several hours... but reportedly works on tertiary amides well.)

Boffis - 29-9-2019 at 08:07

OK, I am now 4 hours into the KOH hydrolysis experiement and a volatile amine is slowly passing over and collecting in 4.5ml of 30% HCl diluted with 20ml of water. For 9.5g of DEET the theory dictates that just over 5.2ml of 30% HCl should be requred to neutralise all of the diethylamine liberated. So when the receiver becomes alkaline I will know that the reaction is about 85% complete. Via a little jiggery pockery I estimate that hydrolysis was about 60% complete at 3.5 hours so I estimate that 8 hours should be sufficient time.

The reaction is being carried as follows: I placed 30ml of ethylene glycol and 20ml of 50% KOH solution in a 100ml conical flask, added a stir bar and then 10ml of 95% DEET (the contents claim 0.1% pyrimethrines and an unspecified amounts of lime oil). The mixture was heated until it just started to boil and then maintained at this temperature and condition. A still head and a reduction adapter act like a crude reflux condenser. The still head feeds into a liebig condenser inclined away from the flask and on the end of it a long receiving spout guides condensate and vapours into a small beaker containing 20ml of water and the HCl. The length and diameter of the spout being sufficient to prevent suck-back. After 4 hours of heating very little has distilled over though what has is cloudy and smalls of limes! The contents of the flask have turned a brown colour and now contain only a little undissolved oil.

Update:

Reflux stoped at 9.25 hours, the flask content has become a clear light brown, tea-like liquid that smells strongly of the amine and more acid had to be added to the collection beaker to hold the amine that distilled over. Hydrolysis would appear to be complete. Tomorrow I'll work up the fractions to see what can be recovered.

[Edited on 29-9-2019 by Boffis]

Tsjerk - 30-9-2019 at 03:25

Quote: Originally posted by Boffis  
Well I also did a test-tube scale test with KOH solution and enough alcohol to give a homogeneous solution and refluxed it for 2 hour with not even the faintest hint of fishy smell so for my next trick I will try more aggresive conditions. I am going try a modification of Dr.Bob's glycol method and catch the amine in dilute HCl.

@Tsjerk: If 70% H2SO4 produces vertually no hydrolysis after 2 hours why should 36% HCl do better? After all the first proton of sulphuric acid is about as ionised as HCl so there isn't really much difference in H+ ion concentration. The only difference is that carbonisation may be less with HCl so a much longer reflux can be used. I don't think you would need to extract the m-toluic acid, I think that it is sufficiently insoluble even in strong HCl to simply precipitate on cooling and can then be filtered off on a glass frit. Recovery of the amine would be best by neutralisation and distillation into fresh HCl and then evaporate this to dryness to remove the excess HCl.

I may try an HCl hydrolysis with a long reflux if the mixture doesn't blacken.


Appearantly 70% sulfuric makes crap out of DEET, I didn't say the acid concentration was too low, more the opposite.

My proposed work up doesn't require distillation.

Boffis - 30-9-2019 at 04:55

Tsjerk. Have you actually tried your proposed method?

My experience already is that there is too much crap even in 95% DEET to simply use any form of hydrolysis and expect to get clean products. I assure you that you will need to purify the amine hydrochloride and distillation is the easiest method as recrystallising the diethylamine hydrochloride is actually difficult due to its high solubility and low thermal solubility gradient.

Tsjerk - 30-9-2019 at 05:44

No I didn't try, I thought that was clear from my post. I have to admit catching diethylamine directly from a KOH hydrolysis is a nice approach.

Boffis - 30-9-2019 at 13:02

I evaporated down the acid collection liquor to recover the diethylamine hydrochloride which worked but the almost white crystalline mass in very deliquescent making it very difficult to manipulate and then get an accurate weight but I'm working on it and the yield looks pretty good. The flask residue was dilute with an equal volume of water, distilled to remove any remaining amine and then treated with charcoal and filtered. The filtrate was still cloudy with tiny droplets of oil but was acidified anyway; fairly coarse straw coloured crystals formed. The crystals were filtered off, washed with a little cold water then petroleum ether (Bp 40-60 C) to remove an oily contaminent and are currently drying.

S.C. Wack - 30-9-2019 at 14:36

Could you not have boiled off your lime oil first? I assume that the amide is less volatile in steam, and that ether lowers solublity of the salt in alcohols. BTW the somewhat pure acid can be an oil.

Boffis - 1-10-2019 at 03:15

The lime oil seems to distil off with the amine so I had to extract the hydrochloric collection liquor with DCM which seemed to work. I then evaporated it to dryness to obtain a very deliquescent white solid.

I am not sure how much of the oil is lime oil and how much is residual toluamide but I suspact there lime oil is added to perfume the product and I doubt that it is 5% more likely <0.5%, hours of boiling with KOH can't do it any good either.

The yield of crude m-toluic acid was 5.060g which is about 75% while the diethylamine hydrochloride weighs about 4g (rapidly deliquescese) so about 70%.

I am going to try and convert the amine to the oxalate salt which is less soluble and not deliquescent.




Pumukli - 2-10-2019 at 10:40

Thanks Boffis for your efforts!

At last it seems proven that one can forget the acid hydrolysis method with this particular amide. The alkaline hydrolysis is the way to go.

You got about 70% amine and 75% acid. They are in good correlation, but it seems that you stopped too soon. Maybe a few more hours boiling would have improved the yield. How many hours did you reflux (refluxed?) the mixture?

Have you tried the oxalic acid method yet? Opinion?

Boffis - 2-10-2019 at 13:11

I am having some problems purifying the toluic acid. I first attempted to recrystallise it from isopropanol with or without the addition of some water but I invariably got an oily precipitate that refused to crystallise. So next I tried dissolving it in sodium hydroxide solution and then evaporating it down until it crystallised: unfortunately it won't. It has evaporated to <10ml of pale straw coloured liquid that does not appear to evaporate further on a steam bath but refuses to crystallise. I have tried scratching the basin etc but to no avail. Anyone has any data on solubilities of m-toluates?

I also carried out today a larger scale experiment (45ml of crude DEET) using essentially the same conditions except that the KOH was added as a solid and then only 20ml of water were added to help create a homogeneous solution. The hydrolysis was run for 10 hour but the initial collection solution containing 20ml of 30% hydrochloric acid was neutralised in 3.5 hour indicating about 80% completion at this point. The final solution in the flask is quite transparent and tea-coloured.

clearly_not_atara - 2-10-2019 at 20:00

http://www.orgsyn.org/demo.aspx?prep=CV3P0820

"Pure white needles of o-toluic acid may be obtained by recrystallization from water (2 l. of water for 20 g. of acid), Darco being used for decolorization. The recovery is about 85% of white needles melting at 101–103°."

Water! Amazing choice, no? Soaps like Na toluate are extremely hydrophilic and might not dry without decomp. However I'm not sure if this technique makes sense when your contaminant is the amide and not the alkane.

Anyway calcium benzoate has very low water solubility so I'm guessing the metatoluate is similar.

Pumukli - 3-10-2019 at 11:02

As a kid I recrystallized nitro-salicylic acid from water. It was quite voluminous but worked. :)

Boffis - 3-10-2019 at 13:27

I actually did a test with 1g in 5ml of water and then added more water in 5ml batches, bringing it to a boil each time before adding the next batch. I got to 50ml, the working capacity of the flask, without getting near complete solution so I gave up and tried IPA instead. I have now found that boiling the diluted sodium salt solution with charcoal and then slowly acidifying while hot with HCl precipitates the acid as pale straw coloured crystals which settle rapidly on cooling and are easily filtered and washed. But I'll give the water method a go. With the new larger batch a longer reaction time and more concentrated KOH has produced a much better, cleaner, cream coloured primary ppt of toluic acid. I haven't worked up the collection liquor yet.

I'm writing up the results of the larger batch with photos for the pre-pub section.

Boffis - 4-10-2019 at 08:40

I am just working up the products from yesterday's larger scale batch and the recovery is nearly quantitative! The recovery of the crude cream coloured m-toluic acid is about 97% and the diethylamine hydrochloride >100% but this is due to problems obtaining it dry and keeping it dry long enough to weigh it. However, it is quite clear that with careful manipulation this reaction can be used to secure both diethylamine and m-toluc acid in very high yields.

Boffis - 5-10-2019 at 12:01

I dried the diethylamine hydrochloride today in a pre-weighed bowl on a steam bath for 2 hours until no more HCl fume could be detected and the material had the appearance of a cream coloured powder and weighed it hot. It gave 23.747g of amine salt which is again about 97% recovery.

I then attempted to recrystallise the crude m-toluic acid from water. I boiled 1 gm of acid with 100ml of water for 20 minutes but it did not dissolve and the water remained colourless. I left the failed experiment to cool. When I returned several hours later the undissolved acid had solidified and stuck to the bottom of the beaker but the aqueous portion was now full of delicate white needles. So not a complete failure but it is going to take more than 150ml of water per gram of acid.

Pumukli - 6-10-2019 at 11:28

Congrats!

Maybe sublimation would be a better option. Benzoic acid sublimes easily and makes great, long needles if heated in a closed jar around 100 C. At least it is my experience.

I'm glad that the recovery is almost quantitative too. Waiting for the prepub article! ;)

S.C. Wack - 6-10-2019 at 12:42

Such a recrystallization (the directions I gave in the other thread) is proven to work; the Merck agrees, giving a solubility of 1:60 in boiling water. If something doesn't dissolve in boiling water it either isn't m-toluic acid or something on the surface isn't. An alternative would be dissolving in alcohol and adding water.

Boffis - 7-10-2019 at 03:13

The recovery of crystalline white m-toluic acid by recrystallisation from boiling water was 67% of good material. Boiling the globules of brownish residue with fresh water failed to recovery any further acid so I presume that the residue is either undecomposed amide or lime oil from the perfume (this toluic acid was from the first experiment in which hydrolysis was not nearly complete).

However, unless you need analytically pure m-toluic acid it is much easier to simply treat the diluted reaction mixture with a good amount of decolourizing charcoal and then acidify it, this gives the product as a soft cream powder. If this is dissolved in the minimum of dilute NaOH solution, charcoal treated again and acidified the product is abtained as a pure white powder in high yield.

fusso - 7-10-2019 at 04:19

But what uses does m-toluic acid have, other than making deet?

Boffis - 7-10-2019 at 08:48

Hi Fusso, I don't know yet but its OTC so worth an investigation :D. Actually I did these experiments simply because I had a bottle of jungle strength insect repellant that I am unlikely to use and because so many people have discussed extracting diethylamne from this source but no one has every published anything like a workable method that they have ACTUALLY tried. I will do this shortly, I am just tidying up a few loose ends.

I was recrystallising some of the crude toluic acid from the first batch today on a larger scale than yesterday and I have discovered an interesting feature that suggests that the acid is a mixture of two substances in about 70:30. The more abundant material crystallises in delicate white needles while the second compound crystallises in scales that are so hydrophobic they float on the water. I suspect the insoluble brown residue is the same material. I am wondering if the DEET contains some of the o or p-isomer?

Just investigated the brown globules which had now solidified so I simply picked them out, they weighed 1.060g from 3.28g of crude acid. They are a crystalline solid, Mp about 80 C and insoluble in water but soluble in hot dilute NaOH.

[Edited on 7-10-2019 by Boffis]

[Edited on 7-10-2019 by Boffis]

S.C. Wack - 7-10-2019 at 16:12

The USA product does not require any decolorizing, as noted in the relevant thread. There was nothing unreacted or unexpected under mild conditions. I suspect that the problems above have roots in not steam distilling contaminants before the reaction, because it's one of the easier syntheses there is.

Boffis - 19-10-2019 at 14:18

I have now tried to recrystallise the better m-touic acid from the larger scale hydrolysis experiment from water as suggested by S.C. Wack and I have found that it can be recrystallised from about 100ml per g giving about 86% recovery of soft, pure white needles (less water can be used but it make filtration impossible).

I have also experimented with the barium salts, this method also looks promising as the volumes of water required are much less and the salt has a steep solubility gradient; it crystallises in dense glassy crystals. Experiments with bought laboratory grade p-toluic acid confirm that the Ba salt is much less soluble. This is analgous to the phthalic acids; the Ba salt of m- or isophthalic acid are much more soluble than the p- or terephthalic acid isomer. I don't have any o-toluic acid but I suspect that it solubility is similar to that of the p- isomer as in the case of the phthalic acids.

I have also found a paper in French that descries the properties of derivatives, particularly the nitro derivatives, of all three toluic acids and there are some interesting properties described for the nitro m-toluic acid derivatives. I have translated part of it and will post it shortly:

Rec. Trav. Chim. de Pays Bas 1901 v20 p149 to 182 toluic acid van Scherpenzeel

draculic acid69 - 19-10-2019 at 15:50

You could turn the toluic acid into toluene the same way benzoic acid to benzene.

Boffis - 20-10-2019 at 08:23

Quote: Originally posted by draculic acid69  
You could turn the toluic acid into toluene the same way benzoic acid to benzene.


Yes but its a bt of a waste.

Boffis - 17-11-2019 at 05:11

I finally got round to distilling the free diethylamine from my hydrochloride. The distillation was easy and the process simple. I dissolved the roughly 46g of crude brown diethylamine hydrochloride in to 30ml of water and added 50ml of 50% sodium hydroxide solution slowly. Both solutions were cold circa 10 C and there was no perceptible exotherm and virtually no amine was lost as vapour. The solution turned cloudy as both salt and the amine separated out. On warming the salt dissolved and two phases formed. The upper brown layer is clearly the amine and rapidly boils off between 55 and 58 C when distillation suddenly stalls. At this point distillation was stopped and the receiver removed, just over 40ml were recovered or about 30g of colourless liquid which is over 80% yield based on 100g of 95% DEET.

Purification of the m-toluic acid is also working well. Fractional crystallisation of the barium salt is the best method I have found. Interestingly I prepared some barium p-toluate from Sigma-Aldrich p-toluic acid and it is clear that the main impurity is NOT this compound so it is probably o-toluic acid to the extent of 5-10%.

Pumukli - 17-11-2019 at 06:24

Does it mean that the DEET you used did contain some (5-10%) diethyl-o-toluamide too? Could this be detected on say TLC?

Boffis - 17-11-2019 at 13:58

Quote: Originally posted by Pumukli  
Does it mean that the DEET you used did contain some (5-10%) diethyl-o-toluamide too? Could this be detected on say TLC?


Yes probably, but I didn't think about the possibility of isomers until I tried to recrystallise the and found the acid melted at a rather low temperature. By this time I had hydrolysed all that I had. I have thought about trying to use TLC or paper chromatography to charaterise the acids and compare them with bought or acids prepared by unambiguous routes (I have p-toluic acid, o-toluidine and o-xylene so this shouldn't be too difficult).

An interesting observation I made while dissolving BaCO3 and m-toluic acid in water it required about 30% more carbonate that theory. I have no explanation for this.

Boffis - 4-12-2019 at 06:42

I have just posted in the prepublication section my write-up on my experiments into the hydrolysis of DEET if anyone wants to talk a look.