Sciencemadness Discussion Board

Aromatic nitration with Guanidine Nitrate

Intergalactic_Captain - 16-1-2009 at 12:26

Attached is a relatively recent paper titled "Guanidinium Nitrate: a novel reagent for aryl nitrations." I found it while searching for ortho-selective nitrations of toluene that didn't require Ac2O - The procedure reportedly yeilds 64:14 (%, not ratio) o:p mononitrotoluenes, though no indication is given as to what happens to the remaining toluene. As no indication is given that m-nitrotoluene is produced, I'm assuming it remains unreacted.

Anyone familiar with this nitration scheme? I can deal with a 64% yeild as long as it's relatively clean - IE, no dinitro products were obtained, implying that a simple crystalisation and/or steam-distillation would yeild o-nitrotoluene with relative ease.

The experimental section;
Quote:

Typical procedure: To a well-stirred mixture of aromatic
compound (0.01mol) and sulfuric acid (85%, 15cm3)
was slowly added guanidinium nitrate 1 (1.22 g,
0.01mol) while maintaining the temperature at 0–5C. After the addition of 1 was complete, the mixture was
stirred for an additional 0.5–3h (Table 1) at the same
temperature or at rt (for entries 21–23). The reaction
mixture was poured onto ice water (100 cm3) and in
the case of anilines it was poured onto ice cold
NaOH solution (20%, 100cm3). The solid obtained
was filtered, washed thoroughly with water and dried.
Where solid was not obtained the aqueous layer was extracted with CHCl3 (4 · 50cm3). The combined CHCl3
layer was washed with 10% Na2CO3 (2 · 25cm3), water
(2 · 25cm3) and then dried (anhyd Na2SO4). After
evaporation of the solvent, a brown residue was obtained,
which was purified by column chromatography
to afford the corresponding nitro compound. All the
compounds synthesised (entries 1–26) gave satisfactory
physical and spectral data consistent with literature
data.


Attachment: guanidinium nitrate nitration.pdf (240kB)
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Intergalactic_Captain - 16-1-2009 at 12:46

Hate to double-post but I can only do one attachment at a time... Here's the paper that the first article was cited in, it deals with nitration with guanindine nitrate, nitroguanidine, urea nitrate, nitrourea, EGDN, AN, and HNO3.

Of interest here is that the general procedure uses 96% H2SO4 rather than 85% and has somewhat different results - Use of guanidine nitrate gave a 42:2:38 o:m:p (% again), along with 3:16 2,6:2,4-DNT yeild from toluene rather than 64:18 o:p. The use of nitrourea gave a 59:41 o:p yield (note that this is the only reaction tested that gave only MNT's with one equivalent and only DNT's with two equivalents) - For my purposes this seems suitable, but nitrourea is tricky to prep and store due to its ready hydrolysis with cold water and atmospheric moisture.

Considering that the only thing that really changed between the two papers is the concentration of the sulfuric acid, I'm a bit stumped as to the differing product distributions of MNT's from guanidine nitrate...My guess is that the more concentrated acid gives rise to a higher nitronium ion concentration leading to higher reactivity, while the lower concentration sacrificed yeild for selectivity in that the overall nitrating mixture was less reactive. Anyone care to chime in on this one?

Attachment: Aromatic nitration using Nitroguanidine and EGDN.pdf (149kB)
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Eclectic - 16-1-2009 at 12:46

Makes you wonder about using ammonium nitrate-sulfuric acid to do the same thing...;)

chemoleo - 16-1-2009 at 18:05

Quote:
Originally posted by Eclectic
Makes you wonder about using ammonium nitrate-sulfuric acid to do the same thing...;)


That was my first thought too - with a slight mechanistic difference:
Quote:
It is well documented
that guanidinium nitrate 1 is converted into nitroguanidine
by the action of sulfuric acid. Further, there is a
report wherein nitroguanidine was used to generate
the nitronium ion in sulfuric acid. However surprisingly,
1 has never been utilised for the nitration of aromatic
compounds. These observations led us to explore
the potential of 1 for nitration of various aromatic
compounds.


That may explain why poly-nitration occurs only to a small degree...otherwise they'd have hardly had cause to publish this!

S.C. Wack - 16-1-2009 at 20:23

In case anyone is wondering how they made the nitrourea, I happen to have the JACS ref (ref 17 of the second paper) that they say that they used, my interest being semicarbazide and the fact that boiling nitrourea with water gives nitrous oxide quantitatively. It says:

"Preparation of Nitrourea.-Nitrourea was prepared by a modification of the original method of Thiele and Lachman. Two hundred grams of carefully dried urea nitrate was added in small portions at a time with stirring to 300 cc. of concd. sulfuric acid (1.84) while the temperature of the mixture was kept below 0°. After the last portion had been added, the cold milky mixture was allowed to stand for one minute and was then poured into a liter of ice and water. The finely-divided white precipitate was collected on the filter, sucked as dry as might be, and, without washing, was immediately dissolved while still wet in boiling alcohol. (The precipitate still contained enough acid to prevent the dearrangement of the nitrourea in boiling alcohol. For a second recrystallization it was found to be unsafe to heat the alcohol above 60°.) The liquid deposited pearly leaflets on cooling. It was chilled in ice water before filtering and the crystals were rinsed with cold alcohol. The alcoholic mother liquors were used for the crystallization of several successive batches. The air-dried product was sufficiently pure without another crystallization. Samples of it have remained unchanged in hard glass bottles for several years; yield, 90% or better.

Why would anyone want to use this instead of HNO3?

[Edited on 16-1-2009 by S.C. Wack]

Sauron - 16-1-2009 at 21:05

Interestingly the result with toluene and guanidine nitrate (64% ortho) was anomalous. All other compounds nitrated in the para position or anyway not in same manner as toluene. Aniline gave 4-nitroaniline; chlorobenzene and bromobenzene gave 4-nitrated products.

A number of members have complained bitterly about the unreliability of reports in Tett.Lett., which is not peer reviewed. The spleen of these critics is most especially reserved for reports issuing from South Asia, as this one does.

So I am sure we will all be interested in your own results, Captain.

chemoleo - 16-1-2009 at 21:59

Another thought:
Quote:
It is well documented
that guanidinium nitrate 1 is converted into nitroguanidine
by the action of sulfuric acid.


I wonder about the control reaction - using commercially prepared nitroguanidine, and H2SO4 (where the amount of the latter is appropriately reduced). Or, using another strong acid for that matter, together with nitroguanidine. Alternatively, how about using other nitro-compounds?


Quote:
Originally posted by Sauron
Tett.Lett., which is not peer reviewed.

As an aside, I was kind of surprised, hearing this (non-peer-reviewed well-known scientific journals are a relatively recent invention to my knowledge)- although I never checked org chem literature on this.... until now:
From here http://www.elsevier.com/wps/find/journaldescription.cws_home...
Quote:

All papers are submitted to referees who advise the editor on the matter of acceptance in accordance with the high standards required, on the understanding that the subject matter has not been previously published and is not under consideration elsewhere. Referees will be asked to distinguish contributions meeting the above requirements and having an element of novelty, timeliness, and urgency that merits publication in the journal. We ask referees to help in the selection of articles that have this breadth and suggest that papers covering narrower aspects of the field be sent to journals specializing in those areas. Referee names are not disclosed, but their views are forwarded by the editor to the authors for consideration. Authors are encouraged to suggest names of several experts in the field when papers are first submitted or at any time in the evaluation process.


[Edited on 17-1-2009 by chemoleo]

Sauron - 17-1-2009 at 00:46

I was merely commenting on what others on this board have complained about Tet Lett publicly. If they are in error take it up with them.

The result with toluene remain anomalous.

It is also worth pointing out that a 64% yield of ortho-nitrotoluene is nothing special. The routine product mix from standard mixed acid nitration of toluene is stated in Ullmann's to be 60% ortho plus or minus 5%. 64% ortho as stated in this paper from guanidinium nitrate is within that range. The "advantage" being put forward is the apparently lower yield of 4-nitrotoluene, but, the authors make no explanation of the fate of a significant amount of the starting toluene.

This looks to me like a "Where's the beef?" commercial.

2-nitrotoluene is always the predominant isomer formed. Separating it from 4-nitrotoluene is facile. If such separation is deemed difficult, several simple procedures are available to give exclusively ortho mononitrotoluene. You have your choice of sulfonation, nitration and desulfonation; nitration of p-toluidine followed by diazotization and alcoholysis; or blocking the 4-position with a t-butyl group then removing it after nitration.

In all three cases no isomer separation is required because only one isomer can form.

The one I have literature on is the nitration of p-toluidine. I am actively investigating the nitration of p-toluenesulfonic acid as an alternative.

S.C. Wack - 17-1-2009 at 07:06

The use of nitroguanidine/H2SO4 may go back to 1926. From the 1929 JACS article: "We have used such a solution [nitrourea/cold conc. H2SO4] for the nitration of aniline, phenol, acet-p-toluide and cinnamic acid, in a manner similar to that in which a sulfuric acid solution of nitroguanidine has been used*." But they do not even mention what products were given with either nitro cpd.

*Proc. Am. Acad. Arts Sci., 61, 437 (1926)

Tet Lett may well have more reproducible detail in 2008 than in 1968.

Sauron - 17-1-2009 at 07:17

Well, at least in the case of p-toluidine, assuming that excess H2SO4 was employed, so that the substrate was in the anilinium form, the only possible product would be 3-nitro-4-methylaniline (2-nitro-p-toluidine).

But the possibilities with phenol and aniline are an open question.