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Question about nitrosation

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In all the articles I've seen where a ketone is nitrosated to a oximoketone like e.g. propiophenone to isonitrosopropiophenone with a alkylnitrite, the alkylnitrite is always added to the reaction mixture either as a gas (methyl- and ethyl nitrite) or as a liquid (butyl- and pentyl nitrites).

I wonder if there is a known reason why the alkylnitrite isn't generated in situ in the reaction mixture? For example: to a solution of propiophenone in IPA is added a saturated solution of sodium nitrite in water followed by a dropwise addition of 50% aq H2SO4. If the water content in the reaction is to be kept to a minumum one could possibly omit the aqueous solution of sodium nitrite and use solid sodium nitrite since water is added with the acid.

This simple change would make such a procedure much easier. Does someone have good reason why this wouldn't work or give lower yields compared to the known methods?

That wouldn't by any chance happen to be a 4-methylpropiophenone would it? ;)  Something that crossed my mind too, but I don't know of any simple ways to reduce the oxime to the amine without affecting the ketone, or at least causing dimerisation due to heat. I'm guessing you do though, and I'm very much looking forward to seeing the results.

Anyway, as to references, the first thing that came into my mind was an old post by Assholium, now archived at, claiming an average 65-70% yield in the articles cited. Here is the link to the Orgsyn article mentioned:; although sodium nitrate is used, the generated methyl nitrite isn't actually used in situ, but it's a start I suppose. If I can get access to the JACS articles I'll try and post them. I'm not sure if such old documents are available online, but I did manage to retrieve a 1952 J. Org. Chem. article online a couple of days ago.

The scientific literature has several examples, one was available to Lego:

Journal of the Chemical Society, Chemical Communications,(1987), (2), 45-7


A solution of NaNO2 (35 g, 0.51 mol) in H2O (70 ml) was added dropwise (hood!) to an ice-cooled, magnetically stirred solution of N,N-diethylacetoacetamid (3b) (78.6 g, 0.5 mol) in glacial acetic acid (100 mL), over ca. 30 min. Upon standing, the product crystallized. Water (100 mL) was added, and the solids were recovered by filtration, washed with H2O, and dried. (The filtrates were discarded.) Yield: 65.3 g (70%), mp 116-118°C. The dense with chunks proved indefinitely stable at room temperature. A sample was recrystallized from aqueous ethanol for analysis, [...]

Another examples were:

NaNO2 + H2SO4
NaNO2 + HNO3
NaNO2 + HCl

Since the actual reagent in all nitrosations is NO+, any source of nitrite will do - the examples in the literature are multiple.

It's always been my impression that alkyl nitrites were used with a sole intent to provide anhydrous conditions of the reaction, and i have no clue if they are really important for propiophenones' nitrosation.

They aren't needed for phenols or anilines, e.g.


Ok, what else could I do but try it myself?

To a 500 ml roundbottom flask equipped with a magnetic stirrer, a thermometer and a addition funnel was added 250 mmol propiophenone (33,5 g), 350 mmol HCl (70 ml of a 5N HCl/IPA) and 100 ml IPA. The addition funnel was charged with a solution of 300 mmol sodium nitrite (20,7 g) dissolved in 30 ml water. The sodium nitrite solution was added dropwise during two hours while the temperature was kept at 25°C by mild cooling. Immediately when the nitrite solution was added sodium chloride started to preciptitate and the temperature rose mildly. The color of the reaction mixture changed from almost colorless to clear yellow. There was never any red fumes from NO2 visible throughout the reaction.

The reaction mixture was allowed to stir for a additional two hours after the addition was complete and was then left over night without stirring at room temp. In the morning the two phases was separated first by decantation then with the aid of a separatory funnel.

The acidic solution was slowly poured poured into 750 mmol NaOH (30 g) dissolved in 200 ml water with cooling and violent stirring. The alkaline solution was extracted with 3x50 ml toluene and the toluene discarded. The alkaline aqueous solution was cooled to 10°C and slowly added to a ice cold solution of 800 mmol HCl in 500 ml water. Isonitrosopropiophenone precipitated out immediately as white crystals and was isolated by filtration.

The still wet isonitrosopropiophenone was divided in two equal portions. One portion (A) was set aside to dry and the other portion (B) hydrolyzed in the following manner:

The wet isonitrosopropiophenone (B) was added to a solution of 400 mmol sulfuric acid (40 g) in 300 ml water and steam distilled until no more oily drops came over. This took about 2 hours. The distillate (little less than 1L) was saturated with NaCl and extracted with 2x100 ml toluene. The combined toluene extracts was dried over MgSO4 and the solvent removed by distillation.

Portion B gave 12,6 g 1-phenyl-1,2-propanedione (68% calculated from propiophenone)
Portion A is not dry yet but I'll add the yield tomorrow.

Ok what have we learned by this?
The alkyl nitrite can very well be generated in situ. Since the yield of the 1,2-diketone isn't too shabby I don't see any reason whatsoever to make any alkyl nitrite separately and add it to the reaction. Unless one wants some amyl nitrite to sniff right before orgasm  ;)

Now with 1-phenyl-1,2-propanedione in hand I will give in to my curiosity of the effects of alpha-pyrrolidinopropiophenone and 2-tert-butylamino-1-phenylpropan-1-one.


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