Sciencemadness Discussion Board

Ethyl centralite synthesis

Priority - 6-8-2008 at 11:20

Hi all,

How do one go about and prepare ethyl centralite or 3-Diethyl-1,3-diphenylurea. Wikipedia entry is just a stub, google search yields -apart from how to detect it- very little, this board hasn't worked out the details of the synthesis yet, the elitists at weapons and explosives forums banned me for asking this question (althogh it was empty there as well, and I have spent hours looking for it).


Such an important compound; so hard to find info on how to make it!

[Edited on 6-8-2008 by Priority]

Ritter - 6-8-2008 at 11:50

Quote:
Originally posted by Priority
Hi all,

How do one go about and prepare ethyl centralite or 3-Diethyl-1,3-diphenylurea. Wikipedia entry is just a stub, google search yields -apart from how to detect it- very little, this board hasn't worked out the details of the synthesis yet, the elitists at weapons and explosives forums banned me for asking this question (althogh it was empty there as well, and I have spent hours looking for it).


Such an important compound; so hard to find info on how to make it!

[Edited on 6-8-2008 by Priority]


Not if you use Google to find the correct nomenclature for your compound (sym-diethyldiphenylurea) & then search the USPTO. Here is one prep patent but it involves phosgene chemistry. Since this stuff is commercially available, I would try to obtain it through commercial channels.

http://www.pat2pdf.org/patents/pat2403068.pdf

Priority - 6-8-2008 at 12:10

Thanks alot Ritter. I've heard about the phosgen pathway, are you aware of any alternatives out there?

Here is the essence of the patent:

page 3 of the patent 2403068

1475 parts by weight of ethylaniline mix (65% of di- and 35% monoethylaniline) heated to 160-170 deg C. Stop heating. Carbonyl chloride (=Phosgen!) gas is added to the liquid at a rate of about 105 parts by weight per hour initialy. Reaction is exothermic and temp will rise to 190 - 210. Temp should be maintained at thes range for the remainder of the reaction period through the controlling of the flow of phosgen. The flow of phosgen is stopped after about 300 parts by weight = the amount equivalent of diethylaniline content.

Authors report that cylindrical nickel reactors (tanks) with heating coils or jacket and preferably externally insulated against heat loss, would do the job.


[Edited on 6-8-2008 by Priority]

Ritter - 6-8-2008 at 12:18

Quote:
Originally posted by Priority
Thanks alot Ritter. I've heard about the phosgene pathway, are you aware of any alternatives out there?


Sure, but only paper chemistry. For instance, it might be possible to react N-ethylaniline with diethyl carbonate to make it. But it sounds like a lot of effort to get something that should be commercially available.

[Edited on 6-8-2008 by Ritter]

Priority - 6-8-2008 at 12:32

As you are already aware, I'm not a organic chemist, Ritter. I also understand your point in obtaining this chemical through commercial channels, but i cannot help wanting to know exactly how one could prepare ethyl centralite (paper chemistry and speculation doesn't matter) . Would you care to elaborate on how much N-ethylaniline with how much diethyl carbonate, under which conditions you THINK MIGHT produce ethyl centralite?

Ritter - 6-8-2008 at 12:50

Quote:
Originally posted by Priority
As you are already aware, I'm not a organic chemist, Ritter. I also understand your point in obtaining this chemical through commercial channels, but i cannot help wanting to know exactly how one could prepare ethyl centralite (paper chemistry and speculation doesn't matter) . Would you care to elaborate on how much N-ethylaniline with how much diethyl carbonate, under which conditions you THINK MIGHT produce ethyl centralite?


If you have no background in chemistry & are only looking for a recipe, I can't help you. Professionals make this stuff on an industrial scale using phosgene, which is a war gas. To steer you into just mixing chemicals without understanding what you're doing & why is a responsibility I'd rather not take on.

Priority - 6-8-2008 at 13:27

Not having a background as a chemist doesn't mean I am a complete moron. Anyone knows that phosgen is a WMD. Even dubya. A Phd is not required. That is the reason I asked if there are alternatives to this preparation, preferably laboratory sized and not industrial scale.

Anyway, thanks alot for your help Ritter. Very friendly of you. If anyone knows of a safe viable labsized prep, please let us all know.

[Edited on 6-8-2008 by Priority]

Klute - 6-8-2008 at 15:38

Beleive him, even properly trained, experienced and well equipped chemist are reluctant at using phosgene. If trying to attempt its use, your are surely going to put you and others at risk.

And if your not a chemist, why do you want to make this compound anyway?

leu - 6-8-2008 at 18:56

It seems that 1,3-Diethyldiphenylurea/N, N-Diethylcarbanilide was developed in Germany, so one might want to try searching the German chemical literature for the information you seek instead of expecting someone else to do it for you :cool:

Sauron - 6-8-2008 at 20:25

Obviously @Priority wants to avoid the use of phosgene.

I am unclear about whether or not this is a paper exercise for Prioruty or whether or not he wants to actually prepare ethyl centralite, and if so, on what scale?

There are safe alternatives to phosgene such as the solid reagent "triphosgene" which is readily prepared by the UV chlorination of dimethyl carbonate. It is commercially available but expensive. Better to make your own. It reacts like phosgene but slower, and is non-volatile.

For alternative preparative routes to various centralite derivatives, none directly involving phosgenation, the attached paper is very helpful.

Its methods might be modified to prepare centralite itself.

SYNTHESIS OF CERTAIN ETHYL, PHENYL, AND NITROPHENYL DERIVATIVES OF UREA2
PHILIP E. WILCOX, W. A. SCHROEDER
J. Org. Chem.; 1950; 15(5); 944-949. DOI: 10.1021/jo01151a004

Other suggestions:

Stepwise alkylation of sym-diphenylurea with ethyl iodide, diethyl sulfate, or triethyl phosphite.

Example of the use of modified method of the JOC paper:

Prepare ethyl isocyanate by method in footnote 4 (diethyl sulfate, KOCN, potassium carbonate heated together cautiously.) I will obtain the Ber. reference.

React ethyl isocyanate with N-ethylaniline to obtain i,3-diethyl-1-phenylurea.

Alkylate that product with your choice of ethylating reagent to obtain the ethyl centralite.

By now you probably can see why phosgenation of N-ethylaniline is the industrial method.

Ethyl centralite is a common chemical commodity used as a modifier for propellants and as a plasticizer, mostly for cellulose.

If you can buy its precursors you can buy ethyl centralite itself.

So is this an academic exercise or what?

[Edited on 7-8-2008 by Sauron]

Attachment: jo01151a004.pdf (122kB)
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Sauron - 6-8-2008 at 23:08

Ullnann's suggests transamination of urea or substituted ureas with amines or amine salts in the melt is a productive route.

I am digging out the references now.

1,3-Diphenylurea can be prepared from aniline and urea.

Diphenylurea and ethylamine (2 mols) under autogenous pressure or ethylamine hydrochloride (more conveniently) give ethyl centralite.

THE UREA DEARRANGEMENT. II
Tenney L. Davis and Kenneth C. Blanchard
JACS 45 pp 1816 - 1820 (1923)
DOI: 10.1021/ja01660a038

THE UREA DEARRANGEMENT
Tenney L. Davis and H. W. Underwood
JACS 44 pp 2595 - 2604 (1922)
DOI: 10.1021/ja01432a028

I have requested these. Note they are by the author of THE CHEMISTRY OF POWDER AND EXPLOSIVES and I have little doubt that ethyl centralite was on his mind when carrying out these studies.

[Edited on 7-8-2008 by Sauron]

Nicodem - 6-8-2008 at 23:38

I don't understand what the original poster wants. If he needs the end compound then why buying N-ethylaniline and all the other reagents needed and wasting time with a lab scale reaction when the end compound itself is already available and cheap? The way the question is asked it does not look likely he wants to practice a reaction either. What kind of an energetic compound is this thing a precursor for anyway?
Quote:
Originally posted by Sauron
Diphenylurea and ethylamine (2 mols) under autogenous pressure or ethylamine hydrochloride (more conveniently) give ethyl centralite.

Are you sure? I think that would give you a mixture of starting materials, aniline, PhNHCONHEt and EtNHCONHEt.
You can obtain EtNPhCONPhEt by heating urea and N-ethylaniline without solvent until no more ammonia evolves. A single recrystallization should give a pure product. Alternatively, for a lab scale reaction you can react N-ethylaniline with carbonyldiimidazole (CDI) in THF at room temperature. The reaction is fast (accompanied by CO2 evolution) and the work up easy.

Sauron - 7-8-2008 at 00:01

CDI is a very good suggestion. It is not particularly cheap, and making it of course requires phosgene or a substitute, so back to square one.

So is transamination of ethylaniline a good idea, or its hydrochloride, with urea.

Am I sure about diphenylurea and ethylamine? Well, I was confident enough to post it, but I have not yet read Davis's patent, and not yet obtained anything but first pages of his JACS articles on this. Ullmann's strongly implies it will work but of course say nothing about details where the devil always abides.

I also am not surer what the thread author wants, but I don't really care as long as the topic is interesting.

Ethyl centralite is not an energetics precursor but rather a burning rate moderator for smokeless powders. Also a plasticizer for cellulose.

But every time I point out that something is cheap and available commercially I get yelled at by those who never like to buy anything, so prepare yourself for their brickbats.

Nicodem - 7-8-2008 at 00:11

Quote:
Originally posted by Sauron
Ethyl centralite is not an energetics precursor but rather a burning rate moderator for smokeless powders. Also a plasticizer for cellulose.

But every time I point out that something is cheap and available commercially I get yelled at by those who never like to buy anything, so prepare yourself for their brickbats.

I just thought it strange that he wants to buy the precursors but not the product itself when it is obvious from his posts that he is not really interested in the chemistry itself. Otherwise, I surely rather see people doing some experimental work from the scratches rather than buying stuff - that is the only way to learn the basics, as you start as close to the beginnings of the chemical chain as possible.

Sauron - 7-8-2008 at 00:46

I concurr that the motives of the thread author are opaque; perhaps he is idly curious or, is letting us do his (academic) homework for him. That is always annoying but I found the problem mildly interesting in its own right and therefore worth some attention. Ritter dismissed all alternatives to phosgenation as "paper chemistry" with which I cordially disagree.

His own suggestion of diethyl carbonate and N-ethylaniline ought to work, Ullmann's gives a sheath of mostly 19th century German refs to this sort of reaction. As diethyl carbonate leads us back to phosgene I see little point in going down that road, although it is not a dead end.

Your suggestion of urea and N-ethylaniline is probably the best, followed by CDI couplins, or a safe phosgenation reagent like triphosgene.

The Davis patent (attached) is not helpful as it is limited to primary alkyl amines and urea, probably because prior art forced him to exclude aryl amines, such as discussed in his JACS articles.

[Edited on 7-8-2008 by Sauron]

Attachment: US1785730.pdf (67kB)
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Sauron - 7-8-2008 at 02:05

Ain't this a kick in the head?

Davis (see attached) teaches that: secondary amines as their hydrochlorides react with urea in boiling water under reflux to give unsym-disubstituted ureas only. Ethylaniline hydrochloride and urea give only 1-pheny-3-ethylurea. No tetrasubstituted ureas are formed.

No reaction took place when ethylaniline base and urea were heated as melt, the melt was in two immiscible phases.

@Nicodem, any literature on the reaction of ethylaniline and urea you described. I hope so because otherwise this route is doom and gloom.

[Edited on 7-8-2008 by Sauron]

Attachment: ja01660a038.pdf (387kB)
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Sauron - 7-8-2008 at 02:07

Here's the first Davis paper describing the melts, rather than the aqueous reflux reactions.

[Edited on 7-8-2008 by Sauron]

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Nicodem - 7-8-2008 at 03:51

Quote:
Originally posted by Sauron
No reaction took place when ethylaniline base and urea were heated as melt, the melt was in two immiscible phases.

@Nicodem, any literature on the reaction of ethylaniline and urea you described. I hope so because otherwise this route is doom and gloom.

I have no references for that or else I would provide them or at least mention that it was actually done. However, I do know from experience that if you heat anilines (or amines) and urea at temperatures of 150-200°C until no more ammonia evolves you get the N,N'-diphenylureas. Though I have to admit that I never tried with N-alkylanilines, but as far as I know it should not make much difference as the method is based on urea<=>cyanate equilibrium and differences in volatility of the aniline and ammonia. I have not read the paper you mention, but perhaps the reaction mixture was simply not heated enough (or the biphasic melt not stirred intensively enough).
Also, if one can prepare EtPhN-CO-NH2 (either using urea or cyanate) it should be possible to heat above 200°C which causes such ureas to decompose to tetrasubstituted ones (EtPhN-CO-NPhEt) and cynuric acid (again no references).

Sauron - 7-8-2008 at 04:22

I posted Davis's two JACS papers so you could read them, so kindly do so before you question Davis's competence to conduct a simple experiment. This is the T.L.Davis whose THE CHEMSITRY OF POWDER AND EXPLOSIVES is a standard reference and in the forum library. Not some nonentity, after all.

I obtained those papers expecting to confirm your statements, not refute them. But, there we are. In the absence of any lit. to the contrary and until such literature is turned up (by you, by me, or whoever) then what choice do we have but to accept Davis's experimental findings? It would be irrational to do otherwise.

Davis says that under the only conditions producing any reaction between N-ethylaniline or its hydrochloride and urea, i.e., aqueoux reflux, the only product, and that in small yield, was 1-phenyl-3-ethylurea.

Similar results were obtained with homologous compounds.

Primary arylamines react readily and in high yield.

Diphenylamine does not react at all.

Do have the courtesy to read the articles I posted when you can find the time and at your convenience of course.

Nicodem - 7-8-2008 at 07:50

Since the job I'm supposed to be doing is too boring, I did a little experiment to see if N-alkylanilines do not work in this reaction while the anilines do (as claimed in the paper Sauron provided above). I heated the mixture of 2 mmol urea with 4 mmol N-methylaniline (I don't have any N-ethylaniline) to reflux in a test tube with the thermometer. The reflux temperature (using a heat gun) slowly increased and the starting biphasic system slowly became homogenous at somewhere around 170°C. I heated for some 15 minutes more and the end temperature of the reflux was about 210°C where it remained more or less constant. A few crystals formed (probably cyanuric acid or some other stuff from urea decomposition). The reaction mixture was diluted with 1M HCl to dissolve any unreacted starting materials and there remained only a little mass that solidified. This was extracted into a ml of ethyl acetate to perform a TLC and IR.
The TLC using a mildly polar mobile phase (petroleum ether : ethyl acetate = 2 : 1) showed two spots, one on the starting line and the other a on the two thirds of the hight of the N-methylaniline spot (which did not show up in the extract since removed with HCl). Developing the TLC again, but this time in ethyl acetate only, demonstrated that the spot on the starting line actually consists of two compounds. So, this makes for three UV absorbing products (containing the UV absorbing anilino moiety): two highly polar (containing the CONH2 group?) and one non polar.
The IR (thin film on NaCl window): 1761 (weak), 1713, 1660, 1585, 1495, 1397 cm-1. So obviously there are at least two or three compounds with a carbonyl group there (or one or two containing nonequivalent carbonyls).
The IR spectra of 1-methyl-1-phenylurea and 1,3-dimethyl-1,3-diphenylurea should be checked to see if any peak corresponds. For 1-methyl-1-phenylurea the IR is supposed to be in Chemical & Pharmaceutical Bulletin, 31 (1983) 423-428. For 1,3-dimethyl-1,3-diphenylurea the spectra is at SDBS where the major peaks are 1662, 1585, 1498 cm-1 which are all present also in the sample within error (to see the spectra you need to search for "N,N'-dimethyl-N,N'-diphenylurea" or "C15H16N2O" since it is not possible to use static link on their site).
So, for now it appears like some substituted ureas do form, but compared to the reaction with N-unsubstituted anilines the reaction is unusually slow and it is questionable if it is useful for preparative use. I do not fell interested enough to run an 1H NMR on the reaction mixture. Besides, I have to continue with the job I'm paid for so I let someone evaluate the results.

Sauron - 7-8-2008 at 09:15

Sorry to hear your current official project is boring, but I guess that is why they call it "work".

Sluggishness and small yield are consistent with Davis. He of course lacked instrumental methods in the early 1920s. But the bottom line remains same: prepareatively useless.

So there remains your proposal using carbonyldiimidazole.

Or phosgenation using hexachlorodimethyl carbonate (triphosgene).

Both starting with N-ethylaniline.

Or, I think we agree, just buy this stuff, which will be cheaper and easier than preparing it.

Priority - 7-8-2008 at 11:02

Sauron and Nicodem, thanks a bunch for this info. Very very friendly of you. And no, you're not doing my homework. This has become more or less a paper exercise. The reason for this post was, I wanted to know if the possibility exists to make high quality homemade triple based smokeless gunpowder from scratch (SAFE and SECURE). The other parts, nitrocellulose and nitroglycerine and diphenylamine are comparatively easy (not safe though) to make. Obviously, putting it all together is very very hard, especially the ethyl centralite part. No wonder everyone buys the stuff. I guess this project is shelved.

[Edited on 7-8-2008 by Priority]

Sauron - 7-8-2008 at 11:33

Ah. You have large bore artillery at home? Picking up where Gerry Bull left off with the Supergun project? Because that is what triple base propellants are all about, lowering bore temperature to extend gun tube life. They have no small arms or medium caliber applications that I know of. About possible applications to rocketry I have no idea.

There's a lot of highly specialized chemical engineering and technology that goes into propellant formulation, manufacture, control of particle size, surface area, stabilization, and a myriad of other factors. Nitrocellulose loves to auto-oxidize. I hardly need to expound on the joys of nitroglycerin. The other component is of course nitroguanidine. Additives are many and varied. Do you have Federoff's series (PATR)?

Anyway I am having a hard time conceptualizing triple base propellant as a home chemistry project. Hats off to you for the maddest mad science idea of the month, maybe the year. Possibly the decade.

@Nicodem, back to an idea I was kicking around upthread:

N,N'-diphenyl-N-ethylurea is readily made from ethyl isocyanate and N-ethylaniline.

Can't one alkylate this to ethyl centralite? Say, iodoethane?

The isocyanate is readily made from diethyl sulfate, potassium cyanate and sodium carbonate by heating with caution as per:

Über Isocyanate, L: Darstellung aliphatischer Isocyanate
Ber., 58 (p 1320-1323)
K. H. Slotta, L. Lorenz

DOI: 10.1002/cber.19250580722


If not I'd like to know why not?

[Edited on 8-8-2008 by Sauron]

Nicodem - 7-8-2008 at 12:08

Well, N,N'-diphenylurea can be ethylated (I saw at least one reference using diethyl sulfate), so I'm sure N-ethyl-N,N'-diphenylurea can be as well. But if you choose alkylation then it is better to start from aniline rather than any isocyanate and prepare N,N'-diphenylurea via urea+aniline which gives nearly quantitative yields (and there are several references besides Davis's paper for this one). Now it is too late for searching the literature - will do so tomorrow.

Sauron - 7-8-2008 at 12:18

Yes, I suppose making sym-diphenylurea and then alkylating both sides would make sense. Lower alkyl isocyanates are pretty unpleasant critters. Well, so is diethyl sulfate for that matter.

No need to look these up, I just wanted to know if it was feasible. I couldn't see why not. Just thought I'd ask.

Thanks.

leu - 7-8-2008 at 13:07

The direct alkylation of DPU has been published in:

A non-phosgene route for the synthesis of alkyl N-phenylcarbamate. From: Chemistry and Industry | Date: June 17, 1991| Author: Ayyangar, Nagaraj; Kalkote, Uttam R.

Recently, a non-phosgene route was reported' for the synthesis of N,N'-diethyldiphenylurea, commercially known as Centralite-I. This involves the alkylation of sym-N,N'-diphenylurea (DPU), (Ia, R=H) with diethyl sulphate in the presence of sodium hydroxide/potassium carbonate and a phase transfer catalyst. A detailed study of the alkylation of DPU by different alkylating agents has also been carried out.

The same basic chemical process was patented in:

Abstract of US5124451
Process for the N-alkylation of ureas by reacting a urea with an alkylating agent in the presence of a solid base and a phase transfer catalyst in a diluent.

:cool:

Attachment: US5124451A1.pdf (443kB)
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leu - 7-8-2008 at 14:01

A nitrocellulose stabilization patent:

Attachment: FR369797A.pdf (72kB)
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leu - 7-8-2008 at 14:04

Another nitrocellulose stabilization patent:

Attachment: FR410239A.pdf (76kB)
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leu - 7-8-2008 at 14:07

And another gunpowder patent:

Attachment: US701591A1.pdf (106kB)
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Sauron - 7-8-2008 at 19:10

Thanks, leu. The patent ought to be interesting. Chem & Ind is unfortunately unavailable online, so requires someone to trek down to a good library.

Annoyingly the full text IS available online from some pay service called HighBeam, $200 a year. They have a phony 7 day "free trial" offer wherein you have to cough up credit card data up front to activate your "free trial" - my mother didn't raise any stupid children so I declined.

I did obtain about half of the next paragraph of the article:

"The importance of methylene-diphenyl isocyanate (III)3 (MDI) in polymer chemistry prompted the development of a method for the preparation of ethylphenyl carbamate (EPC), (IIa, R=H, R'=Et), a key intermediate in the synthesis of MDI. The known procedures for the ... "

which tells us what their sudden interest in diethyl diphenylurea is all about, and it isn't propellants.

That Austrian-owned US patent is indeed similar chemistry but only explicated the alkylation of urea and monoalkyl ureas, and only with alkyl bromides (and one example of a chloride). No phenylureas are mentioned, possibly because of prior art. Most of the examples are of preps of unsymmetrical dialkylureas from monoalkylureas.

Thus, the Chem & Ind paper appears to be the only one "on point" for the specific target compound and with comparative details for various alkylating agents.



[Edited on 8-8-2008 by Sauron]

Sauron - 7-8-2008 at 21:03

And as it turns out, the above 1991 paper merely points to a 1988 paper in same journal, pp 599-600, by same principle authot A.Ayyangar, entitled "A Non-Phosgene Route to N,N'-Diethyldiphenylurea" and this is our target.

This 1988 paper is cited in the EP patent corresponding to the US patent posted above.

That EP patent (in German) is attached.

[Edited on 8-8-2008 by Sauron]

Attachment: EP0471983A1.pdf (87kB)
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Sauron - 7-8-2008 at 23:24

According to the introductory section of that US patent above, all prior art teaches that N-alkylation of ureas is impossible. Specifically, only O-alkylation occurs with alkyl halides, or, with dialkyl sulfates, the products are the isouronium salts.

Only in the presence of a PTC (or DMSO) do alkyl halides react with ureas to form alkylureas.

We are only able to surmise (until the text becomes available) that N.Ayyangar's 1988 Chem.Ind. paper teaches that PTC also alters the path of the alkylation of ureas with dialkyl sulfates to allow succesful N-alkylation without rearrangemnent to the isourea.

And meanwhile we can but speculate that iodoethane or bromoethane could be used instead of diethyl sulfate in the PTC assisted ethylation of diphenylurea.

The EP version of the patent does include a CA citation of the 1988 paper, but all attempts to google the author's name, the title as given, or both return only that patent, or the 1991 article, equally inaccessible, and which is on derivatives (carbamates and isocyanates) rather than our target ethyl centralite proper.

N.Ayyangar turns up in Google Books as a contributor or editor of a text on Phase Transfer Catalysis. But otherwise, this chemist's publications appear to be limited to the above and a paper on production of codeine from morphine. (And that may or not be actually the same author.)

The patent also cites a paper by another author in Synthesis, on N-alkylation of thioureas. I will retrieve this one. I have Synthesis here on CDs.

[Edited on 8-8-2008 by Sauron]

Nicodem - 7-8-2008 at 23:57

Quote:
Originally posted by Sauron
@Nicodem, back to an idea I was kicking around upthread:

N,N'-diphenyl-N-ethylurea is readily made from ethyl isocyanate and N-ethylaniline.

Can't one alkylate this to ethyl centralite? Say, iodoethane?

The isocyanate is readily made from diethyl sulfate, potassium cyanate and sodium carbonate by heating with caution as per:

Just a minor note since I did not read this carefully enough yesterday. Using EtNCO on PhNHEt would give you EtNH-CO-NEtPh of which N-ethylation would give Et2N-CO-NEtPh and not the target compound. To use isocyanates you would have to react phenyl isocyanate with PhNHEt and then N-ethylate to obtain the target urea PhEtN-CO-NEtPh.

Sauron - 8-8-2008 at 00:44

Thanks. I was going too fast and transposed those.

Anyway the isocyanate route and the trisubstituted urea intermediate are basically out the window, replaced by diphenylurea alkylation with PTC, Et2SO4, NaOH/sodium carbonate and a little PTC. Those are my best guesses at present till this article from Chem.Ind. turns up.

The bill of materials, to borrow a term from another discipline, thus looks like:

Urea and aniline -> DPU
ethanol and H2SO4 -> diethyl sulfate
NaOH and sodium carbonate
Your favorite PTC

[Edited on 8-8-2008 by Sauron]

Sauron - 8-8-2008 at 00:57

The Synthesis article cited in EP above wasfrom 1984 and concerned N-alkylation of cyclic thioureas, specifically crown ethers containing thiourea moiety.

In an earlier paper in same series the authors found that such cyclic thioureas could be S-alkylated, then N-alkylated as the isothiouronium salts and hydrolyzed to the N-alkylated cyclic ureas.

In the subsequent paper nonaqueous conditions were employed and the isothiouronium salts were main products, these readily thermolyzed to the cyclic N,N'-dialkylthioureas.

PTC was used in both instances, but alkylation initially proceeded via the usual S-attack and isomerization.

The papers are nonetheless instructive. I have combined them into a single pdf for posting here.


[Edited on 8-8-2008 by Sauron]

Attachment: s-1982-29837.pdf (187kB)
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Sauron - 8-8-2008 at 03:06

Here is the CA abstract for the 1988 Chem Ind article.


"A non-phosgene route for the synthesis of sym-N,N'-diethyldiphenylurea. Ayyangar, Nagaraj R.; Chowdhary, Anil R.; Kalkote, Uttam R.; Natu, Arvind A. Natl. Chem. Lab., Pune, India. Chemistry & Industry (London, United Kingdom) (1988), (18), 599-600. CODEN: CHINAG ISSN: 0009-3068. Journal written in English. CAN 110:134854 AN 1989:134854 CAPLUS

Abstract

Condensation of PhNH2 with H2NCONH2 in alc. or excess PhNH2 gave 88% and 98% PhNHCONHPh (I) resp. Phase transfer-catalyzed alkylation of I with Et2SO4, powd. NaOH and K2CO3 in xylene in the presence Et3BuN+Br- gave PhEtNCONEtPh in 93% yield."

>90% from aniline and urea in two steps. Now that's a prep!

So now I really want the full text.

Sauron - 8-8-2008 at 22:52

Here's the take from PATR 2700 Volume 3: useful or at least interesting perspective on the technological applications of the centralites, and a precis on the phosgenation of N-ethylaniline on a lab scale.

I did not consult this earlier simply because I anticipated that no non-phosgene methods for manufacture would be mentioned. Michler's original prep (1876) is referenced but he employed a carbamyl chloride, itself made of course from phosgene.

Still, this might be helpful in case anyone wants to go the long way round using triphosgene as a safe substitute.



[Edited on 9-8-2008 by Sauron]

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vulture - 9-8-2008 at 06:59

Sauron, could you please condense your posts into a small number as possible, unless you are using attachments? Your posting sequence is usually well within the edit function time window.

Sauron - 10-8-2008 at 00:01

Thanks, vulture, I will endeavor to do so at all times.



[Edited on 11-8-2008 by Sauron]

Sauron - 12-8-2008 at 00:03

Thanks to gsd, here is the long awaited full text of the Chem & Ind paper from 1988 (attached.)

The aniline and urea were reacted in alcohol or excess aniline under reflux, giving 88% (in alcohol) or 98% (in aniline) of sym-diphenylurea. Aniline was recycled without reduction in yield. Further details of this step were not given, but are very adequately covered in the literature.

The alkylation step is elucidated on a half molar basis as follows:

0.5 mol sym-siphenylurea in 800 ml xylene is stirred at 200 rpm and 80 C for 1 hour with 2.5 mol powdered NaOH, 0.5 mol powdered potassium carbonate (anhydrous), and 100 mmol triethylbutylammonium chloride. Then 1.1 mol freshly distilled diethyl sulfate was added and stirring and heating continued for two more hours. The sym-diethyldiphenylurea was worked up and recrystallized from ethanol, 93% yield.

sym-N,N'dimethyldiphenylurea was prepared in 91% yield by same method. It is known commercially as methyl centralite or centralite-2.

Other PTCs besides Et3BuN+Cl- were used with equal success including Bu4N+Br- and BnEt3N+Br-.

There are some interesting references in this paper. I am digging up two of them.


[Edited on 12-8-2008 by Sauron]

Attachment: A Non-phosgene Route for the Synthesis of Diethyldiphenylurea.pdf (822kB)
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Klute - 12-8-2008 at 05:10

Oh I'm jealous of those 3 DVDs :)

Sauron - 13-8-2008 at 04:29

The paper references a 1985 Polish patent 126,634 but I found the Polish Patent Office databases to be wholly useless. Anyway it is probably in Polish.

By the way, I misspoke above. The source of the paper was Axt not gsd. Thanks, Axt!

[Edited on 14-8-2008 by Sauron]

Klute - 17-9-2008 at 14:05

This following article might be helpfull for anyone interested in preparing diphenylurea:

A rapid microwave assisted synthesis of N, N'-diarylureas under solvent-free condition
S Sarveswari & T K Raja
Indian Journal of Chemistry, Section B; (2)45, 546-547 (2006)
IPC: Int.Cl.7 C 07 C

Abstract:
A novel microwave assisted phosgene-free synthesis of N,N¢-diaryl ureas under solvent free conditions has been described.

Sauron - 17-9-2008 at 15:03

Diphenylurea is prepared under solvent free conditions anyway, from aniline and urea, so I do not see the utility of substituting ethyl acetoacetate for urea or of having to employ a MW which will restrict the scale.

At most, diphenylurea prep is only solvated with excess aniline which is recyclable to next batch, or with ethanol. Excess aniline gives essentially quant. yields.