using bisulfite adducts w/ nitroalkanes

joe_aldehyde · huxleys associate

swija read the method of kamlet: from benzaldehyde bisulfite adduct to phenylnitropropanol and was wondering if the bisulfite adduct could be used in conjunction with the traditional rxn. pathway to phenylnitropenes.

since the method of kamlet involves KOH in aq. solution as the catalyst, there is no problem with the solubility of the bisulfite adduct. when water is kept out of the reaction as is usually the case in michael additions of aldehydes with nitroalkanes, solubility of the bisulfite adduct ought to be considerably decreased.

has anybody ever thought about/tried using the bisulfite adduct directly, and how would the layout of the rxn. look?

furthermore, what is the most efficient method of regaining aldehydes from bisulfite adducts with minimum loss? swija found that P/NP extraction from dilute acid which liberates the aldehyde from the adduct gives shitty yields, whatever NP solvent is used.
may liberating the aldehyde with dilute acid (hydrochloric), evaporating the water (on the rotavap) and extracting the residue (NaCl, Aldehydes) be more worthwile, or will the liberated SO2/HCl in solution attack the aldehydes while it becomes more and more concentrated?

anime · Thu Aug 25, 2005 10:03 am

joe, why not form the nitro alcohol, react it with acetic anhydride and then do a CTH with potassium formate and pd/c. You'll reduce both acetate and nitro groups to yield the [edit: amine]

look at the hive for the thread greatest CTH documented (or something along those lines). I'll try to post the patent tomorrow.

joe_aldehyde · huxleys associate

anime, why would i want an aldehyde? and why now the need for acetic anhydride? i think you misread my post. i'm very well aware that CTHs will be favourable in my case but that was not the question Sad

anime · Thu Aug 25, 2005 8:32 pm

ahh I meant amine...amine...
the acetic anhydride acetylates the OH group which can be then reduced via Pd/C.
Pd/C reduces both the nitro group and the acetylated group.
Acetic anhydride can be prepared from chloroacetate and sodium acetate in GAA.

Bushroot · Thu Aug 25, 2005 9:06 pm

joe_aldehyde, if I understand correctly you mean if is it possible to react bisulfite adduct with nitroethane. Probably yes, I dont think the Na2SO3 that would be formed would interfere with the reaction. But it would add you extra work after you get the nitropropene oil - before crystallizing it you'll need to filter it off from the sodium sulfite.
And IMHO - KOH catalized condensation of aldehydes with nitroalkanes is a real pain in the ass. Takes too much time and needs babysitting to watch for the temperature (if it goes above 5C you'll end up with red coloured crap).
I'd recommend you to waste a day for getting the free aldehyde, and then do the condensation with some amine catalist. Because the nitropropene will be much more pure (easier to crystallize and better yield)

I too have noted that HCl is no good in making aldehydes and ketones from bisulfite adducts. NaOH (used in equivalent molar amounts) will give quantitative yields (almost 100%). It's also possible to use common baking soda, with almost as good result.

anime · Thu Aug 25, 2005 9:13 pm

thats fine the sodium sulfite isn't very soluable in anhydrous IPA, or non-polar solvents. It wouldn't be too difficult to extract the nitropropene in DCM, remove the dcm and then recrystallize.
IMO if the condensation works on the bisulfite complex I'd opt for this method.

On forming the bisulfite complex for aldehydes, is it the same proceedure as for ketones?

64bandil · Busy Bee

Do not use Pd/C + formate for nitroalcohol reduction. The formate gets oxidised to carbonate, which is basic enough to function as a poor catalyst for the condensation. This means that much nitroetane and benzaldehyde will form in the solution. The nitroethane gets reduced to ethylamine, which will condense with the benzaldehyde, get reduced again and form N-Ethylbenzylamine. The latter is very very hard to remove from the final product and makes a product thats impossible to purify.

Now, Zn + HCl is much more functional. Gives a nice product every time (just go sloooow on the acid addition).

joe_aldehyde · huxleys associate

bandil, swija thought Zn/HCl only worked with amalgamated Zn? i'm pretty sure you have some reference or experimental procedure at hand. swija just tried the method out of some patent about norephedrine precursors, employing 26ml EtNO2, 14ml Triethanolamine and 10ml Benzaldehyde. let it sit at -5degC for 4 hours, can't really tell if anything in there has reacted at all - at least, some water froze out (which it did after mixing EtNO2 with catalyst and putting it in the freezer before Benzaldehyde addition).
i'm really being left in the dark here, whats the usual workup on that kind of substrate? neutralizing the catalyst, salting out the product?

64bandil · Busy Bee

1: Neturalize the catalyst
2: Strip the alcoholic solvent
3: Dissolve in DCM
4: Extract with aq. bisulfute. to remove any benzaldehyde remaining.
5: Strip DCM
6: Dissolve in proper solvent (cant remember which, check the org. procedure).
7: Add activated zinc
8: Stirr
9: Drip in HCl slowly
10: Extract (remember to use the Lemminger reaction to get rid of the zinc complex's)

Work up...