obituary (Hive Addict)
07-26-01 03:03
No 198944
      nitro mechanism  Bookmark   

In the case of article synlett no7 1064-1066 yr 2000 on Rhodium's site, obit would like to propose a improvement on the nitroalkane synthesis based on the authors views.  In the article the authors state [quote]..we have observed that when a mixture of NaNO2-AcOH-HCl is treated with a variety of alcohols the corresponding nitro compounds are formed in excellent yields." 

obit's opinion on this:  good, we have some proof of nitro formation.  octanol is used (aliphatic- what we want) in good yeilds of 87%

"In our case we believe that HCl/HNO2 protonates the alcohol which dissociates to the carbonium ion which reacts with NO2- present in the mixture giving the corresponding nitroalkanes in excellent yeilds"

obit's view:  ok, we have carbonium ions formed, so the stonger the acid, the faster the protonation and then subsequent formation of the carbocation. 

"In the case of entry 2,3 and 7-14 (some of which are primary aliphatic alcohols, which we want), more obvious fast expulsion of a proton from the *adjacent carbon* (alkene synthesis) is suppressed by a more rapid nucleophilic attack of NO2- at the carbocation resulting , in most cases in the nitroalkanes. 

obit's view: ok, we need to provide a large concentration of the NO2- to give good results.  to supply the carbocation by protonation/dissociation and NO2(-) by nitrous acid, we need a strong, concentrated acid. 

in obit's words from the text given: IR data shows no formation of the nitrite esters (yes!laughsmile).  all of the data shows the formation of the respective nitro compounds or their respective alkenes.note1

note 1: fortunately for us, none of the aliphatic alcohols resulted in the alkene!  the reason: the nucleophilic attack by the NO2- is much faster than the adjacent deprotonation to give the alkenes. 

obituary wants to suggest the improvement of simply using H2SO4 chilled instead of the HCl for increase in strength of acid and no water.  plus, the H2SO4 is excellent at dehydration- yes, this means formation of ethylene, but only at higher temps, for our purposes and low temps, it would serve to pick up the water off of the alcohol when protonated.  plus, with a stronger acid, the HNO2 would be formed faster delivering a greater concentration of the NO2 ion. 

Now, obit knows that there may not be a large difference in yeilds, but it makes the synth more versatile and perhaps more volumetrically efficient. 

comments?  esp. Rhodium, Lugh, Osmium, Unobtainium, Stonium, and anybody else that has some practical experience in mechanism derivation and use. 
 
 
 
 
    obituary
(Hive Addict)
07-26-01 03:07
No 198945
      Re: nitro mechanism  Bookmark   

perhaps HCl (anhyd) could be bubbled in as a strong acid, that would cut down on volume and give a continous source of strong acid.  Plus, the bottom addition would mean any nitrogen oxides formed (if any) would have to travel through the solution. 
 
 
 
 
    Antoncho
(Official Hive Translator)
07-26-01 09:05
No 199007
      Re: nitro mechanism  Bookmark   

Yess'... smile

You know, Obit, i actually tried this rxn (inspired by your post, BTW) while the Hive was down and it failed - that is, the way i did it, it failed. However I'm quite confident that it can be made to work - at least, to some degree. It's just unscalable as it is now. You can't increase the amt of alc used w/out increasing the amt of the solvent likewise, cause it seems that when the conc-tion of water hits a certain point all turns to nitrite.

I recall that after the 1st fuckup i decided to scale the procedure from the article 10x in respect to alc/nitrite, but adding them in portions of 2x and letting react. The 1st batch worked just as described - ie, no bubbles. After it sat there for like 40 min i added another portion and even bee4 i added HCl it started to fucken bubble away.

I'm certainly no advanced theoretic smile but adding conc. H2SO4 instead of HCl would IMHO work better - in fact, that idea has crossed my mind then and i tried to carry it out (BTW, based on the calculations derived from the 1st portion "success" above it could give a conceivable yield) but made a fatal mistake of using toluene instead of DCM that time, and that just didn't fucken work - duhhh...:)

Well, let me repeat once again that i feel that this rxn has a potential ranging from "another alternative" to "revolutionary"; but some serious labor must be done bee4 it works. One more idea that i'd like to propose is using some water-removing agent like MgSO4, fuck my life, this water has to bee removed somehow.

I'm not gonna work on this in the immediate future, though, beecause DCM is so expensive here that i can't really afford experimenting much w/it. Dear Obituary... wink, since it was you who first reported a success w/this... would you uhh...smilelaughwink

Looking forward to hearing from you,

Antoncho

P.S. Oh yeah - i was trying to make nitromethane, so it was methanol i used; i suspect it was not quite dry, BTW.
 
 
 
 
    Osmium
(Stoni's sexual toy)
07-26-01 10:49
No 199024
      Re: nitro mechanism  Bookmark   

Iīm not convinced that the reaction can be done anhydrous at all, but I have to admit I havenīt looked at it closely yet.

Is H2SO4 really a stronger acid than HCl? And if so, by how much?  And will HNO2 really form in H2SO4?
 
 
 
 
    lugh
(Hive Bee)
07-26-01 14:20
No 199048
      Re: nitro mechanism  Bookmark   

Reacting alcohols with sodium nitrite and sulfuric acid is the general route to obtaining nitrite esters, it's doubtful that this will be useful for producing the nitro compound. Gassing may prove effective, but as Osmium stated, the water may be needed for the reaction pathway to lead to the nitroalkane. Is it possible  this works through the rare SNi (frontside attack) mechanism?
 
 
 
 
    obituary
(Hive Addict)
07-26-01 20:58
No 199108
      Re: nitro mechanism  Bookmark   

as described by the patent it has to be an SN1 b/c a carbocation is formed by protonation and removal of water.  also, being a primary alcohol, it would be favored in this manner.  this also means that a protic solvent would be best (ethanol, acetic acid, various other acids- as is seen in the synth)

in regards to Osmium, obit has thought about where the HNO2 would go without water- is it soluble in AA?  if so, no need for water, unless it appreciably slows down the rxn.  (less soluble,less concentration, slower)  but as Antoncho has suggested, the H2SO4 route is used more often for the synthesis of the nitrite.  now, we could always isomerize our nitrite, correct? still possibly good yeilds!  simply pass over asbestos catalyst @ 115-120*C and viola! nitro.

what this bee would like to know is, why is the DCM included at all?  it makes no sense at this point.  perhaps understanding its role in the rxn would lead us to better inovations. 

(obit thinking to self-"Where is Rhodium's voice in this?")

Antoncho, what is the reasoning behind the formation of the nitrite instead of the nitro compound when using the sulfuric?  believe it caused by incomplete separation and dissociation of the the ion from the sodium before attaching to the new molecule, hence the oxygen connects versus the nitrogen.  thoughts? 


 
 
 
 
    Rhodium
(Chief Bee)
07-26-01 21:55
No 199120
      Re: nitro mechanism  Bookmark   

To be really honest, I have no idea why the reaction works at all.

../rhodium
 
 
 
 
    obituary
(Hive Addict)
07-26-01 22:46
No 199129
      Re: nitro mechanism  Bookmark   

Rhodium, what are your qualms with the rxn?  what part is giving you a problem?  the patent gives good reasoning for the formation of the products given (except maybe the formation of nitrites may seem more probable, but shown not to be formed- again, yes!!)  everything procedes as the literature explains and to obit it seems reasonable

 
 
 
 
    Rhodium
(Chief Bee)
07-26-01 23:14
No 199137
      Re: nitro mechanism  Bookmark   

Personally, I don't know why the nitro compound is formed in this reaction instead of the nitrite ester, it seems so similar to reactions which just produces nitrites. I'm just a chemistry undergraduate, so don't ask me about mechanisms wink

../rhodium
 
 
 
 
    obituary
(Hive Addict)
07-26-01 23:39
No 199144
      Re: nitro mechanism  Bookmark   

currently, said mix (50x rxn w/ some modification) is running on about 12 hr mark.  filtered off most of the crystalline mass and added the mix to 150ml DCM with a little bit (15ml) h2o,  bubbling gently like a slight reflux would.  placed back on stirrer- going to wait till tomorrow to finish
 
 
 
 
    lugh
(Hive Bee)
07-27-01 04:34
No 199191
      Re: nitro mechanism  Bookmark   

A hypothetical reaction mechanism for this reaction is that first the alcohol is chlorinated, second a nucleophilic replacement of the chlorine by the nitrite ion occurs, then the nitroalkane is removed from the aqueous layer by the DCM. If this mechanism is what's really going on, then it is perhaps a PTC could enhance this reaction, though on the other hand, a PTC could promote formation of the nitrite ester. Reducing the amount of DCM or changing the acids as suggested would be counterproductive if this hypothesis is correct.
 
 
 
 
    Rhodium
(Chief Bee)
07-27-01 05:50
No 199198
      Re: nitro mechanism  Bookmark   

A way to test that hypothesis would be to use HBr or HI in the reaction, and check for differences in the outcome, and to use the same reaction conditions with ethyl chloride and other ethyl halides.

../rhodium
 
 
 
 
    lugh
(Hive Bee)
07-27-01 13:15
No 199286
      Re: nitro mechanism  Bookmark   

Yes, and tlc of the original published reaction and the modified procedure using changes in the halogen acid  or otherwise would be very useful, along with other characterization tests if possible.smile
 
 
 
 
    Antoncho
(Official Hive Translator)
07-27-01 23:00
No 199394
      May i suggest a mechanism?  Bookmark   

Well i think i have a couple of thoughts on all this.

First, although it wasn't my suggestion that H2SO4 is used to make nitrites i still think that it should work, possibly better. The bottom line is that HCl is just as suitable for producing nitrites as is sulfuric, it's just not used because HCl vapors would contaminate the nitrite.

I'm quite certain that formation of alkylhalogenides has nothing to do with this rxn at all, because HCl turns into NaCl the very instant it hits the rxn surface. You can't make ethyl chloride w/NaCl smile

Now to the possible rxn mechanism. This is an exert from  ../rhodium/chemistry /nitrite2nitro.txt:


The theory of isomeric conversion not being adequate to explain the formation of the entire quantity of the nitro-compound actually produced, the formation of unstable intermediate compounds becomes the only alternative explanation of the formation of the aliphatic nitro-compounds. This additive hypothesis is
summarised thus: Nitrous acid, which forms aliphatic nitrites, and not nitro-compounds with alcohols, evidently possesses the oxylic constitution HO-N=O, and the inorganic nitrites, including silver and mercurous nitrites, being obtained simply by the neutralisation of nitrous acid with inorganic oxides, would also possess the same constitution. When the alkyl iodides react with silver or mercurous nitrite, or when the alkyl sulphates react with alkali  nitrites, two reactions take place, namely, (1) the aliphatic nitrites are obtained by direct interchange, and (2) unstable intermediate compounds are formed, which decompose with the formation of nitro-compounds thus:

              AgO-N=O + C2H5I => AgO-N(C2H5)-OI => C2H5-NO2 + AgI
           KO-N=O + C2H5KSO4 => KO-N(C2H5)-OKSO4 => C2H5-NO2 + K2SO4



I vaguely recall seeing another paper on the web that explained the mechanism (speaking of NaNO2/DMF) some other way, but i can't remember it for my life's sake.

OK, anyway. From what i have recently learned :) NO2- ion has two nucleophilic centers, N and O smile which obviously  compete w/each other in rxns like ours. In this case it would mean that we get nitro as soon as nitrogen prevales and forms the menioned above adduct. Now as you easily can see in NO2- ion one of the oxygenes has an extra electrone which makes it a better nucleophil than the N atom. Now, in undissociated HNO2 it doesn't have that advantage and makes nitration possible. It's entirely consistent w/the fact that in all nitrations (AgNO2; EtBr/DMSO; NaHSO3) the nitro carrier is not dissociated.
Which brings us to suggest that we need some undissociated HNO2, which means - unhydrous conds!
Now, the role of acid. NaNO2 doesn't react w/glacial AcOH at all. In fact, glacial AcOH doesn't even react w/carbonates. So, just like Antibody2 suggested in the old thread, it is to create some initial amt of HNO2 that we need acid for. As soon as some water appears in the rxn, AcOH itself begins to dissociate and liberate HNO2  - and indeed, when you add some acid, all the nitrite immediately changes its appearance but - note that - no NO2 is formed! Which means that we have a HNO2/AcOH soln. As the alcohol is processed, though, more water appears into the rxn which causes more HNO2 to dissociate and form nitrite, which formes yet more water - and faster than w/nitroalkane... The snowball effect. It does indeed start very gradually - first a couple of tiny bubbles, in ten minutes a fucken volcano.
Again, the purpose of adding CH2Cl2 seems to be its forming an emulsion with water/AcOH. Since all alcohols in the original article were water-insoluble, they'd stay in the DCM reacting w/undissociated HNO2, while its dissociated portion was contained in the aqueous medium. I think that's why the yields were so high. In our case the alcohol is water soluble, and that's badfrown.

So...Where does that leave us? Obviously, the water must be removed somehow. But i really see no way to do this... The point is to remove the extra water and not dehydrate HNO2 lest it should fly away - H2SO4's no good...

Another idea that comes to my mind is rxn between alc. and NO2/NO mixture at, say, 130 C. I suggest that catalytic trace amt of water is needed here - see nitrite2nitro.txt, section "Influence of moisture" for details. - BTW, this fact also supports the HNO2 hypothesiscool One might say that it's the same as isomerizing nitrites - well, no it's not the same, the yields should be much better, since the rate limiting step in that isomerization is the dissociation of nitrite, not the formation of nitrocompd. In practice, that could mean that instead of designing a 3 meter all-glass anakonda one could settle w/smth that fits into his usual oil bath...- BTW, with a 2 meter pipe filled w/asbesthos the claimed yield is around 25%...yuck.

Well, that's it for now. Please feel free to flame me if i fucked smth up. Any ideas are highly appreciated.

Antoncho