| Pages:
1
2 |
Sauron
International Hazard
Posts: 5351
Registered: 22-12-2006
Location: Barad-Dur, Mordor
Member Is Offline
Mood: metastable
|
|
2-Bromo-6-nitrotoluene
I have need to prepare this compound. The literature recommends starting with p-toluidine, dinitrating that, and eliminating the 4-amino group as
diazonium compound, to get pure 2,6-dinitrotoluene (epsilon-DNT).
One nitro group is reduced with ammonium sulfide, the resulting amino grroup is then subjected to the Sandmeyer reaction to obtain the target
compound.
So I am hunting for procedure for the dinitration.
Also soliciting alternative reducing agents for the -NO2 -> -NH2
Ammonium sulfide gives a crummy 45%
It would be unpolitic to try to buy the 2,6-DNT as it is explosive and probably controlled here.
The target compound is absurdly expensive from Aldrich. No way I will pay $100/g for something I can make.
I would also appreciate a critique of the following alternative scheme:
p-toluenesulfonic acid is mononitrated then monobrominated.
The sulfonic acid group is then removed.
This is simpler than the lit. route, so what is wrong with it?
Sic gorgeamus a los subjectatus nunc.
|
|
|
not_important
International Hazard
Posts: 3873
Registered: 21-7-2006
Member Is Offline
Mood: No Mood
|
|
Sulfifr reduction is one of the best general routes for reducing some of the nitro groups in a poly-nitro aromatic, other common reduction methods are
usually more difficult to control and give even worse yields SFAIK.
Seems that the p-toluenesulfonic route is running into some fairly strong deactivation, although I can see why you like it. Starting with p-toluic
acid (should I say crithminic acid?) would be a less desirable related route, as the decarboxylation would likely be more difficult that the
desulfanation.
I'll have to think a bit on this.
|
|
|
Sauron
International Hazard
Posts: 5351
Registered: 22-12-2006
Location: Barad-Dur, Mordor
Member Is Offline
Mood: metastable
|
|
Fundamental Processes od Dye Chemistry p 165 9forum library) has mononitration of p-toluidine at -5 to 0 C with mixed acid (sans NOx) and teaches that
under the stated conditions, nitration occurs only ortho to the Me group and not ortho to the amino.
Modifying this to dinitration ought to be straightforward.
I have not yet looked in Davis or Urbanski, my source for the prep of epsilon-DNT from p-toluidine was the ACS monograph on TNT in forum library. See
chapter on the mono and dinitrotoluenes. Epsilon = 2,6-DNT.
The temporary blocking of the para position in nitration to drive nitration to the ortho position(s) is taught in Org.Syn. and Vogel as well as the
dye chem text for the example of p-acetanilide-sulfonic acid. With the two PGs removed the nitroaniline is oxidized to o-phenylenediamine.
Sic gorgeamus a los subjectatus nunc.
|
|
|
not_important
International Hazard
Posts: 3873
Registered: 21-7-2006
Member Is Offline
Mood: No Mood
|
|
I was thinking more of bromination of the SO3H+NO2 containing beastie, dinitration with somewhat forcing conditions would be likely to go.
|
|
|
Sauron
International Hazard
Posts: 5351
Registered: 22-12-2006
Location: Barad-Dur, Mordor
Member Is Offline
Mood: metastable
|
|
The same ref. (Dye Chemistry) has preps for the ortho chloro p-toluidines. Again the Me group overrides the amino. Interesting because I have a copy
of a patent that teaches the opposite.
It appears that the dinitro-p-toluidine is well known in energetics circles as 4-ADNT (4-amino-2,6-dinitrotoluene) and per PATR 2700 (Federoff et al)
it is usually prepared by reduction of TNT. PATR also says (in volume 9 under dinitro-toluidines) that it can be made by nitration of the
mononitro-p-toluidine, for which I have a prep from the Dye Chem book. I will continue to look for a one-step to this or an alternate pre for 2,6-DNT
cleanly without having to muck around with sorting out isomers.
The 2-position of 6-nitro-4-toluenesulfonic acid is activated by both the Me and the nitro, and deactivated only by the sulfonic acid. So I think
bromination as well as nitration ought to work there, obviously if bromination works I will save a step or two and have no need to introduce a second
NO2. If the lit. is mum then only one way to find out.
FINALLY I found what I was looking for in Urbanski volume 1. A reference to the unambiguous preparation of 2,6-dinitrotoluene free from other isomers,
by diazotization and alcoholysis of dinitro-p-toluidine:
H,Kolbe, J.prakt.Chem 5, pp427-431 (1872.)
[Edited on 3-1-2009 by Sauron]
Sic gorgeamus a los subjectatus nunc.
|
|
|
stoichiometric_steve
National Hazard
Posts: 819
Registered: 14-12-2005
Member Is Offline
Mood: satyric
|
|
| Quote: | Originally posted by Sauron
I have need to prepare this compound. |
Ah, going for Wang-Hendrickson?
|
|
|
not_important
International Hazard
Posts: 3873
Registered: 21-7-2006
Member Is Offline
Mood: No Mood
|
|
| Quote: | Originally posted by Sauron
The same ref. (Dye Chemistry) has preps for the ortho chloro p-toluidines. Again the Me group overrides the amino. Interesting because I have a copy
of a patent that teaches the opposite.
The 2-position of 6-nitro-4-toluenesulfonic acid is activated by both the Me and the nitro, and deactivated only by the sulfonic acid.
|
Aromatic amino groups in strong acid are in the form of the ammonium salt which is deactivating meta-directing, so there's no 'overriding' -
o,p-activating Me plus o,p-deactivating ammonium ion para to the Me. If not in acid solution then amino overrides alkyl.
Nitro is deactivating, just less deactivating to the meta positions than to the o/p ones. So -SO3H and -NO2 on the same ring should be fairly
deactivating overall, the Me- just isn't that activating, although the 6- position will be the least deactivated.
|
|
|
Sauron
International Hazard
Posts: 5351
Registered: 22-12-2006
Location: Barad-Dur, Mordor
Member Is Offline
Mood: metastable
|
|
@steve
Yes, but as I have a thread going on the W-H that is hardly a Holmesian deduction.ccMore of a Lestrade.
I figure I will use 3-chloropicolinic acid so as to specifically NOT make LA.
@not_important:
I am awaiting the old German lit.
Meanwhile I found a prep in same dye chem book of 2-chloro-6-nitrotoluene. They did not block the 4-position, but 2/3 of the product went ortho as
desired, and this was seperable from the 2,4- byproduct by fractionation in vacuo with a high reflux ration (15-20).
I could go this route, using Br2 rather than Cl2, and would need to ascertain the constants of the two isomers from the lit.
(Aldrich website:
the 2-nitro-6-bromotoluene bp 143 C/22 mm
and the 2-nitro-4-chlorotoluene bp 130 C/12 mm
They sell both
So the question boils down to: is it better to do a dinitration (in one or two steps), then a diazotization, a reduction and then a Sandmeyer? That's
4-5 steps. Or just a mononitration andbromination then a fractionation? If I buy the 2-nitrotoluene then, it's only two steps. In the fractionation,
the ortho, ortho product comes over first, after a small forerun of starting material, so I would not have to much around recovering the 2,3 product
or working over the eutectic.
[Edited on 3-1-2009 by Sauron]
[Edited on 3-1-2009 by Sauron]
Attachment: Pages 160-161_of_dye_chemistry.pdf (174kB)
This file has been downloaded 915 times
Sic gorgeamus a los subjectatus nunc.
|
|
|
Sauron
International Hazard
Posts: 5351
Registered: 22-12-2006
Location: Barad-Dur, Mordor
Member Is Offline
Mood: metastable
|
|
And here is the longer alternative
[Edited on 3-1-2009 by Sauron]
Attachment: Pages 165-167 dye_chemistry-.pdf (189kB)
This file has been downloaded 691 times
Sic gorgeamus a los subjectatus nunc.
|
|
|
not_important
International Hazard
Posts: 3873
Registered: 21-7-2006
Member Is Offline
Mood: No Mood
|
|
A possible problem with halogenation of the nitrotoluene is the tendency of bromine to substitute para over ortho. For toluene the o/p distribution
is roughly 40:60 (meta < 1%) while for chlorine the ratio is reversed. For cheap raw materials and easy separation this may not be a problem.
55289-35-5
2-Bromo-6-nitrotoluene
bp 143 °C/22 mmHg
136.0 °C / 8.0mmHg
108-110 / 0.3 mmHg
mp 38-40 °C
60956-26-5
4-Bromo-2-nitrotoluene
Boiling point, 130 ºC (12 mmHg)
256 ºC
Melting point 43-46 ºC
|
|
|
Sauron
International Hazard
Posts: 5351
Registered: 22-12-2006
Location: Barad-Dur, Mordor
Member Is Offline
Mood: metastable
|
|
That would certainly push things toward the dinitro-p-toluidine route.
The following is from Ullmann's section on nitroaromaticsulphonic acids, specifically nitrotoluenesulphonic acids.
Nitrotoluenesulfonic acids have properties similar to 3-nitrobenzenesulfonic acids and are reduced to toluidinesulfonic acids, which sometimes
offer advantages over anilinesulfonic acids as colorant intermediates. The methyl group introduces an additional functionality, leading to alternative
derivatives, mainly via oxidation reactions.
2-Nitrotoluene-4-sulfonic acid[97-06-3] (18), 3-nitro-4-methylbenzenesulfonic acid C7H7NO5S, Mr 217.20, crystallizes from water as pale yellow
hygroscopic needles of the dihydrate (mp 92 °C, decomp. < 245 °C).
2-Nitrotoluene-4-sulfonic acid[97-06-3] (18), 3-nitro-4-methylbenzenesulfonic acid C7H7NO5S, Mr 217.20, crystallizes from water as pale yellow
hygroscopic needles of the dihydrate (mp 92 °C, decomp. < 245 °C).
[1] B.I.O.S., F.I.A.T. reports: German Dyestuffs and Dyestuffs Intermediates, Including Manufacturing Processes, Plant Design and Research
Data 1945 –1948.
2,6-Dinitrotoluene-4-sulfonic acid [88-90-4] (160), 3,5-dinitro-4-methylbenzenesulfonic acid, C7H6N2O7S, Mr 262.20, crystallizes as a hydrate
in the form of pale yellow crystals, which soften at 110 °C, dehydrate at 140 °C, and melt at 165 °C.
Production. 2-Nitrotoluene is sulfonated to form 2-nitrotoluene-4-sulfonic acid; the reaction mixture is diluted with 90 % sulfuric acid, and
sodium nitrate is added over 6 h at 80 °C. After a further 1 h at this temperature the reaction mass is poured into water and the sodium salt of the
product is salted out by addition of sodium sulfate. After being washed acid-free with brine, the yield of 160is ca. 80 %.
These are major industrial chemical commodities in the dyestuffs industry.
So, my question is, cannot we alter the order of preparation?
Start with p-toluenesulphonic acid, nitrate that?
I have no particular qualms about o-nitrotoluene as a feedstock but I'd rather not have to use oleum.
[Edited on 3-1-2009 by Sauron]
Sic gorgeamus a los subjectatus nunc.
|
|
|
Sauron
International Hazard
Posts: 5351
Registered: 22-12-2006
Location: Barad-Dur, Mordor
Member Is Offline
Mood: metastable
|
|
I found a patent on separation of DNT isomers by fractional distillation at 20 mbar (15 mm Hg) The inventor claims purity of 99.9% for 2,6-DNT, but I
think fractionation of DNT mixtures is not a very pregnant idea. Sounds like an explosion waiting to happen.
The patent does contain a reference to a Can J Chem paper describing the diazotization of 4-amino-2,6-DNT (dinitro-p-toluidine).
Attached below, bundled into one pdf
[Edited on 4-1-2009 by Sauron]
Attachment: DNT.pdf (732kB)
This file has been downloaded 782 times
Sic gorgeamus a los subjectatus nunc.
|
|
|
Sauron
International Hazard
Posts: 5351
Registered: 22-12-2006
Location: Barad-Dur, Mordor
Member Is Offline
Mood: metastable
|
|
Another method cited as prior art in the US patent above is the pyrolysis of 2,6-dinitrophenylacetic acid referenced from Ann. 379, p 152 (1911) and
in particular p 181.
I will obtain this but I suspect that dinitration of PA will produce an isomer mix, unless the 4-position is blocked just as in the case of toluene,
either with a sulfonic acid or with an amino group tractible to diazotization.
If there are any surprises I will let you know.
The main surprise I would expect is that, unless this PA decarboxylates very easily at a relatively low temperature, this is an explosion waiting to
happen. At least a deflagartion, and not something amenable to scale-up.
W. Borsche, D. Rantscheff
Ann. 379, 152-182 (1911)
DOI: 10.1002/jlac.19113790203
[Edited on 4-1-2009 by Sauron]
Sic gorgeamus a los subjectatus nunc.
|
|
|
Sauron
International Hazard
Posts: 5351
Registered: 22-12-2006
Location: Barad-Dur, Mordor
Member Is Offline
Mood: metastable
|
|
The other approach to 6-halo-2-nitrotoluenes is also documented in Ullmann's section on nitro aromatics, particularly o-nitrochlorobenzene and similar
toluene derivatives. These include the toluidines and the sulphonic acids.
Some literature is turned up in the process.
4.3. Chloronitrotoluenes
Of the ten chloronitrotoluene isomers available, only five are of potential technical interest. Both nitration of chlorotoluenes and chlorination of
nitrotoluenes result in isomer problems, but the latter is more substituent directive.
2-Chloro-6-nitrotoluene[83-42-1] (17), 6-chloro-2-nitrotoluene, 2-nitro-6- chloro-1-methylbenzene, C7H6ClNO2 , Mr 171.58, mp 37.5 °C, b p 238 °C
(101 kPa).
Production. Chlorination of 2-nitrotoluene, in a process similar to the chlorination of nitrobenzene, gives a mixture of 6- chloro (80 %) and 4-
chloro (20 %) isomers. The major component 17is separated by vacuum distillation.
Uses. Reduction of 17 gives 6- chloro-o-toluidine [87-63-8] (Fast Scarlet TR Base, 84) which, apart from forming azo dyes, is used to produce
2,6-dichlorotoluene, by Sandmeyer reaction, for conversion to 2,6-dichlorobenzaldehyde.
----------------------------------------------
6-Nitro-o-toluidine[603-83-8] (122), 2-methyl-3-nitroaniline, C7H8N2O2 , Mr 152.15, mp 92 °C, b p 305 °C, d 415 1.378, crystallizes from ethanol as
yellow leaflets.
Production. 6-Nitro-o-toluidine is produced by sulfide reduction of 2,6-dinitrotoluene in a process similar to that for 3-nitroaniline (Section 5.1.
Nitroanilines) or by controlled hydrogenation of 2,6-dinitrotoluene with palladium on a carbon catalyst [62].
[62] M. Lounasmaa, Acta Chem. Scand. 22 (1968) 2388 –2390. (NB attached below)
Nitration of 2-nitrotoluene yields a mixture of 2,4-dinitrotoluene and 2,6-dinitrotoluene. Chlorination in the presence of iron or Friedel – Crafts
catalysts yields a mixture of 4-chloro-2-nitrotoluene (16) and 2-chloro-6-nitrotoluene (17), whereas in the absence of iron, 2-nitrobenzyl chloride
[612-23-7] (28) or 2-chlorotoluene is formed, depending on reaction conditions.
[Edited on 4-1-2009 by Sauron]
Attachment: acta_vol_22_p2388-2390.pdf (405kB)
This file has been downloaded 745 times
Sic gorgeamus a los subjectatus nunc.
|
|
|
Ebao-lu
Unregistered
Posts: N/A
Registered: N/A
Member Is Offline
|
|
P-position may be also protected by t-Bu, and it is removed with excess of benzene(transalkylation) in the presence of Friedel-Crafts or acidic
catalysts. Probably, you may add benzene after the chlorination/bromination step, while the catalyst is there. But there is another hassle with making
the t-butyl precursor
[sorry, really no literature(from avaliable sources), but found that making p-tertbutyl toluene is a problem because of low regioselectivity (20-30%
meta). ]
[Edited on 5-1-2009 by Ebao-lu]
|
|
|
Sauron
International Hazard
Posts: 5351
Registered: 22-12-2006
Location: Barad-Dur, Mordor
Member Is Offline
Mood: metastable
|
|
Nice. And lit. on this?
(much later) I calculate not.
-----------------
To summarize, the best route to 2-bromo-6-nitrotoluene is from p-toluidine dinitration in the cold and with a large excess of H2SO4 so the toluidine
is in the form of the anilinium salt. Under these conditions only ortho nitration (to the methyl) occurs. The resulting 4-amino-2,6-dinitrotoluene is
well known as a reduction product of TNT. Diazotization and alcoholysis provides pure 2,6-DNT. Monoreduction gives 2-methyl-3-nitroaniline, or
6-nitro-o-toluidine.
When using the toluidine nomenclature be careful. Present conventions number the toluidines 1-methyl while older literature numbers then 1-amino,
which can lead to confusion.
This compound is a dye intermediate and as such is commercially available.
From 2-methyl-3-nitroaniline, one step (Sandmeyer) to 6-bromo-2-nitromethane.
I don' think it is going to get any easier than this.
[Edited on 6-1-2009 by Sauron]
Sic gorgeamus a los subjectatus nunc.
|
|
|
Nicodem
Super Moderator
Posts: 4230
Registered: 28-12-2004
Member Is Offline
Mood: No Mood
|
|
| Quote: | Originally posted by Sauron
Nice. And lit. on this? |
The use of t-Bu protection of aromatic positions is one of the most common ones (it is easy to introduce and remove, it does not reduce the
Pi-nucleophilicity and it is not prone to ipso substitution like most other protections such as -SO3H). If you are interested there is a nice
review by M. Tashiro in Synthesis (1979) 921-936.
…there is a human touch of the cultist “believer” in every theorist that he must struggle against as being
unworthy of the scientist. Some of the greatest men of science have publicly repudiated a theory which earlier they hotly defended. In this lies their
scientific temper, not in the scientific defense of the theory. - Weston La Barre (Ghost Dance, 1972)
Read the The ScienceMadness Guidelines!
|
|
|
Sauron
International Hazard
Posts: 5351
Registered: 22-12-2006
Location: Barad-Dur, Mordor
Member Is Offline
Mood: metastable
|
|
While I was looking at sulfonation, or more precisely, looking at starting from commercial pTsOH, the very standard prep of 2,6-DNT is the dinitration
of p-toluidine sulfate in the cold.
Reducing the DNT gets 2-methyl-3-nitroaniline. The simple fact is that this is a very common chemical commodity used in the dye industry for preparing
disperse dyes for syeing polyesters.
The dinitro-p-toluidine is also a degradation product of TNT.
So there really is little need to investigate the synthesis any further, is there? With the aminonitrotoluene at hand, all we are looking at is a
Sandmeyer to the thread title target compound. The isobutene cylinder can stay on the shelf.
I am no stranger to tBu groups, per my long interest in peptide synthesis. I merely wanted ephoton to realize that including some lit. citation is de
riguer.
But thanks.
Sic gorgeamus a los subjectatus nunc.
|
|
|
Sauron
International Hazard
Posts: 5351
Registered: 22-12-2006
Location: Barad-Dur, Mordor
Member Is Offline
Mood: metastable
|
|
The following sequence is supported in the literature.
1. One-pot sulfonation of chlorobenzene followed by addition of two mol-eq KNO3 to produce 4-chloro-3,5-dinitrobenzenesulfonic acid
2. Desulfonation
3. Reaction with sodiomalonic ester followed by hydrolysis and decarboxylation to produce 2,6-dinitrophenylacetic acid
4. decarboxylation to 2,6-DNT
I have two criticisms before even looking at yields.
-- I see no advantage to this route over the sulfonation and dinitration of p-toluidine
2. The final thermolytic decarboxylation had better be mild, as all the dinitrotoluenes are high explosives.
Yield claimed in the acetoacetic acid step 75%
I will attach the article.
The prep of 2,6-dinitrochlorobenzene is described in Ullmann's under nitrohalosulfonic acids in the Nitroaromatics chapter (Nitro Compounds -
Aromatic)
[Edited on 12-1-2009 by Sauron]
Attachment: diniclbenz.pdf (1.2MB)
This file has been downloaded 738 times
Sic gorgeamus a los subjectatus nunc.
|
|
|
Artemisia
Harmless
Posts: 17
Registered: 19-1-2009
Member Is Offline
Mood: No Mood
|
|
A high yielding nitro reduction reagent is Iron powder/ NH4Cl. I'll try to find you a ref, but it works in much higher yield than 45%. I've got >65
before. Sorry if you already know about this method, Im new to this board so dont know how much everyone knows....
|
|
|
Artemisia
Harmless
Posts: 17
Registered: 19-1-2009
Member Is Offline
Mood: No Mood
|
|
Actually, thinking about it, this would probably work nicely. You should get an overall yield of around 20%. Not bad considering how cheap p-toluidine
is.
1. Mononitrate p-toluidine with NaHSO4/ NaNO2 over Silica in DCM (this works nicely but isnt well known)
2. Brominate the ortho position with NaBrO3/ H3PO4.
3. Diazotise and remove the p-amino group.
4. Reduce the NO2--->NH2 with Fe/NH4Cl.
|
|
|
Sauron
International Hazard
Posts: 5351
Registered: 22-12-2006
Location: Barad-Dur, Mordor
Member Is Offline
Mood: metastable
|
|
Thanks. Actually we can skip step 4 as it is 6-bromo-2-nitrotoluene that I want.
Very nice. The p-toluidine has to be in the anilinium sulface form for the nitro group to enter ortho th -Me doesn't it? Else it will enter ortho to
-NH2 I suspect, not what I want.
Can't I do steps 1 and 2 to p-toluenesulfonic acid, and then knock off the sulfonic acid moiety with H2SO4?
Sic gorgeamus a los subjectatus nunc.
|
|
|
Artemisia
Harmless
Posts: 17
Registered: 19-1-2009
Member Is Offline
Mood: No Mood
|
|
even better actually as the sulfonic acid would ensure substitution ortho to the methyl and meta to the sulfonic acid. I dont know how well sulfonic
acids can be removed with H2SO4 though. have you ever tried doing it?
|
|
|
sparkgap
International Hazard
Posts: 1234
Registered: 16-1-2005
Location: not where you think
Member Is Offline
Mood: chaotropic
|
|
Well, in fuming sulfuric acid, your sulfonation is an equilibrium reaction.  All
Sauron needs to do is shift his equilibrium towards the un-sulfonated product. The other functional groups aren't the kind to be perturbed by fuming
sulfuric acid anyways... 
sparky (~_~)
"What's UTFSE? I keep hearing about it, but I can't be arsed to search for the answer..."
|
|
|
Sauron
International Hazard
Posts: 5351
Registered: 22-12-2006
Location: Barad-Dur, Mordor
Member Is Offline
Mood: metastable
|
|
Several examples of desulphonation with H2SO4 in Org.Syn. and many more in "Fundamental Processes of Sye Chemistry" (forum library.
My interest in preparing this compound or its immediate precursor 2-methyl-3-nitroaniline, was stimulated by obscenely high prices from Aldrich, and
the other usual suspects. But I have now found the aniline for <$1/g in kilo quantity and at that price I am just a Sandmeyer away from target.
The substituted aniline is a dye intermediate usually prepared by half-reduction (with ammonium sulfide) of 2,6-DNT. Anyway it is a bulk chemical.
Sic gorgeamus a los subjectatus nunc.
|
|
|
| Pages:
1
2 |
![[*]](images/xpblue/default_icon.gif){kind=icon}
