[Babcock_Hall]

We have been trying some test reactions using previously obtained protocols (one from the 1930s), and the preliminary H-1 results from the first protocol is very promising. Today I found the two papers below, which use TFA and a metal-ion salt of nitrate or nitrite.  We are looking for references to other TFA-based methods, just in case our first methods fail.

https://pubs.rsc.org/en/content/articlepdf/1978/p1/p19780001076
S Uemura et al., J Chem Soc Perkin I 1076-1079 1978.
https://jcsp.org.pk/ArticleUpload/1368-6161-1-RV.pdf
Munawar and Khalid 2004
From the first reference:  "A typical procedure is given. To a stirred solution of toluene (0.184 g, 2 mmol) in trifluoroacetic acid (15 ml) was added solid sodium nitrite (0.414g, 6 mmol) in one portion a t 25 "C. The resulted dark brown mixture was stirred for 8 h at 25 "C during which period the mixture turned orange, water (100 ml) was added, and the solution was extracted with benzene (3 x 50 ml)...Reactions with sodium nitrate were carried out similarly."  The substrates in the second reference were haloaromatics, and the conditions were 90 °C.  I don't think that their substrates are similar to ours, and I doubt that I would try this method as is.

[rolnor]

Nice! You can do a lot of chemistry with thiophenes that is not possible with benzenes. If you lithiate thiophene you can alkylate it with alkyl iodides, you dont need to make a cuprate like you need with phenyl lithiums for example.

[Babcock_Hall]

The thiophenes we have tested so far have modest antimicrobial activity.  Our second small-scale nitration using slightly different conditions also went well.  We will combine them to test our purification conditions and to work out any bugs.  We also have a medium-scale nitration reaction waiting in the wings once the first column is completed.

[Babcock_Hall]

Probably worth trying the 90% before screwing around to try to make the 98% yourself. Both are nasty stuff, even in small amounts they spit out NOx smoke in surprising amounts just from being exposed to the air. It lives up to the name "fuming nitric acid" I assure you.

Thank you for this suggestion.  We have now performed a medium-scale nitration using 90% nitric acid by adapting a protocol that had been used on a derivative of pyrrole, and we purified it via silica.  We had to use more acetic anhydride to address solubility of the starting thiophene aldehyde.  The yield was 38%, which is certainly adequate for our purposes and in the same range as what was reported for a similar thiophene aldehyde.

[Babcock_Hall]

We are short one signal in the C-13 spectrum; we could use LC-MS data to confirm this product.

[rolnor]

The signals may be overlapping. You can change solvent to pull them apart or use INEPT if they have different multiplicity I think.

[Babcock_Hall]

Good idea.  We have made other nitro-aromatics or -heteroaromatics and the carbon attached to the nitrogen is often broader than the others.