Sciencemadness Discussion Board
Not logged in [Login ]
Go To Bottom

Printable Version  
Author: Subject: The seemingly anomalous reduction of 3,5-dinitrosalicylamide to 3-amino 5-nitrosalicylamide by iron/HCl
nitro-genes
International Hazard
*****




Posts: 1029
Registered: 5-4-2005
Member Is Offline


[*] posted on 2-7-2020 at 16:30
The seemingly anomalous reduction of 3,5-dinitrosalicylamide to 3-amino 5-nitrosalicylamide by iron/HCl


3,5-dinitrosalicylic acid is a generally used reagent for colorimetric determination of reducing sugar concentrations. Direct nitration of salicylic acid seems somewhat difficult though, due to some accompanying decarboxylation/ipso nitration of the carboxylgroup, even at low temperatures. The KNO3/SA mediated nitration of methylsalicylate (oil of wintergreen) is much easier, no decarboxylation is observed at all and the 3,5-dinitro methylsalicylate obtained has a very sharp melting point (122 C) with almost theoretical yield. A small amount of the dinitro methylsalicylate was hydrolysed to yield the free 3,5-dinitrosalicylic acid and was stored for glucose determination.

Since I had made more than enough of the 3,5-dinitro salicylic acid, I decided to see if some other experiments could be performed. While reading through some articles of Meldola (:D), I noticed that they mentioned that the hydrochloride salt of 3-amino 5-nitrosalicylic acid was very insoluble in excess HCl. So I was curious if reduction of 3,5-dinitrosalicylic acid using ethanol/HCl/Fe(0) would be somewhat more selective towards mono-nitro reduction due to this property. Under no circumstances that were tested did this reduction work to produce any of the mono-nitro product however (as is usually the case for reductions using nascent hydrogen).

Assuming some ligand interactions could be helpful during the reduction, I reacted some of the 3,5-dinitro methylsalicylate with a large excess of about 35% ammonia, to form 3,5-dinitrosalicylamide, which crystallized as beautiful cubic blocks (mp. 182 C) from a large volume of hot water (it is much less soluble in water than dinitrosalicylic itself).

The reduction of 3,5-dinitrosalicylamide was performed as follows: 1 g of the 3,5-dinitrosalicylamide was dissolved in 50 ml 98% ethanol and 10 ml 31% HCl was added. While at 50 deg C, 0.8 g steel wool was added and left to react for about 20 minutes at 40-50 C, forming a white precipitate of feathery crystals. When the white precipitate was filtered off and washed with some distilled water, the colour instantly changed to a bright orange. The product reacted with nitrous acid to give the corresponding diazoquinone. Yield of 3-amino 5-nitrosalicylamide (or free acid?) was 52% of theory.

Still somehwat puzzled why 3,5-dinitro salicylic refused to give any mono-nitro product, the same reduction scheme was repeated for 3,5-dinitro methylsalicylate. Also here, no precipitate of the mono-nitro reduction product could be obtained.

So to summarise the ethanol/HCl/Fe(0) mediated reductions performed:

Experiment 1. 3,5 dinitro salicylamide --> white precipitate of hydrochloride salt of 3-amino 5-nitro salicylamide (52% yield)

Experiment 2. 3,5 dinitro salicylic acid --> no precipitate, seemingly mostly overreduction products and some starting product (didn't test very well for this though). Reaction mix turned dark red upon dilution

Experiment 3. 3,5 dinitro methylsalicylate --> no precipitate, seemingly mostly overreduction products and some starting product, reaction mix turned dark red upon dilution

Curious why only the amide seems to give some yield of the mono-reduction product, since the hydrochloride salt of 3-amino 5-nitro salicylic should be at least equally insoluble in the reaction mixture, as described by Meldola. Is the ligand action of the amide group towards the iron indeed the most likely scenario why only the reduction of the 3,5 dinitrosalicylamide yields any of the mono-nitro product? Or would the amide group react with some transient reduction product or other wise help in selectivity towards mono-reduction? Something else completely?

Would also be curious to see if using dry HCl gas dissolved in dry ethanol would be able to produce higher yields than simply adding some 31% HCl. Anyway, couldn't find any examples where an amide group was assisting selective nitro reduction, so seemed interesting to mention at least. :)

[Edited on 3-7-2020 by nitro-genes]

[Edited on 3-7-2020 by nitro-genes]
View user's profile View All Posts By User
Boffis
International Hazard
*****




Posts: 1612
Registered: 1-5-2011
Member Is Offline

Mood: No Mood

[*] posted on 3-7-2020 at 00:51


@nitro-genes; Have you tried sodium sulphide type reducing agents as they tend to give selective o-nitro group reduction (the 3 position in this case)? I have never seen it expressly stated but the abundant literature on the selectivity of the sulphide /alkali hydrogen sulphide reduction of nitro phenol tends to suggest that these systems are anomalous and other reducing agents are less specific or prefer p-nitro groups. If the p-amino-nitrosalicylic acid doesn't form a sparingly soluble hydrochloride you simply might not see a ppt of the hydrochloride.

I must admit that having tried to prepare 3,5-dinitrosalicylic acid myself I can confirm that getting the picric acid out of the product is a bugger. I'll have to try the nitration of the ester. I must say that I am intrigued by the selective reduction of the nitro amide by Fe/acid.
View user's profile View All Posts By User
nitro-genes
International Hazard
*****




Posts: 1029
Registered: 5-4-2005
Member Is Offline


[*] posted on 3-7-2020 at 04:19


Don't own any sulphides myself unfortunately... however, the sulphide mediated reduction of 3,5-dinitrosalicylic is mentioned in an old paper by Meldola (attachment). This was taken from "Meldola, Raphael, Henry Stennett Foster, and Rainald Brightman. "XLVIII.—Attempts to prepare asymmetric quinquevalent nitrogen compounds. Part I. 5-Aminosalicylic acid and related compounds." Journal of the Chemical Society, Transactions 111 (1917): 533-546."

No yield is stated for this reduction, but it seems not an easy synthesis by any means, curious if the methylester would be easier to reduce. Also curious indeed what is going on with the iron mediated reduction. Perhaps it just relates to the solubility and/or ratio of all the different isomers of the corresponding hydrochloride salts and free acids like you mention. Maybe 3-amino 5-nitro salicylamide is just the least soluble in ethanol. Maybe simply using dry HCl in dry ethanol would also precipitate the 3-amino products for 3,5-dinitrosalicylic and it's methyl ester indeed. Or maybe the amide group of 3,5-dinitrosalicylamide changes the o-p isomer distrubition. It seemed an easy reduction though... just add ethanol/HCl/Iron --> stirr at RT until precipitation of the hydrochloride salt stopped --> filter --> wash...done :)

5-nitro 3-aminosalicylic from sulphide mediated reduction of 3,5-dinitrosalicylic acid .jpg - 127kB

[Edited on 3-7-2020 by nitro-genes]
View user's profile View All Posts By User

  Go To Top