Iodination of p-dimethoxybenzene under non-organic solvent free conditions without organic solvents?

A solvent is a solvent is a - mediator? - reagent! -....

Striving for the solventfree crown of green chemistry the authors do what chemists always do since the times of alchemy: They twist the nomenclatura to achieve what they are after.

Of course it´s nonsense to say 30% H2O2 is a reagent or "mediator" and with UHP this is a reagent IN water as solvent.

The stunning result they present says that 1,4-dimethoxybenzene yields nothing with iodine and H2O2 30% w/w in water, whilst in the earlier studies they are referring to, iodine and UHP and water in the same molar amounts regarding active H2O, iodine, water gave 94%.
Thats puzzling and the logical conclusion - also founded by a look on table 1 - is that they fucked something nicely up and now they don´t know if it was in the earlier experiments or now.

Resume: Water when with H2O2 dissolved is no solvent anymore but transmutates into a - eh - now reactand not - yep! - lets say "mediator".



/ORG

PS: This "mediator" speak got pretty hip, didn´t it? And iodine too! Searching turned up a big pile on iodinations...

PS2: The 94% will be somewhere in this heap of articles:

M. Jereb, M. Zupan, S. Stavber, Chem. Commun. 2004,
2614–2615; b) G. Stavber, M. Zupan, M. Jereb, S. Stavber,
Org. Lett. 2004, 6, 4973–4976; c) M. Jereb, J. Iskra, M. Zupan,
S. Stavber, Lett. Org. Chem. 2005, 2, 465–468; d) A.
Podgor{ek, S. Stavber, M. Zupan, J. Iskra, Tetrahedron Lett.
2006, 47, 1097–1099; e) I. Pravst, M. Zupan, S. Stavber,
Green Chem. 2006, 8, 1001–1005; f) J. Pavlinac, M. Zupan,
S. Stavber, J. Org. Chem. 2006, 71, 1027–1032; g) J. Pavlinac,
M. Zupan, S. Stavber, Synthesis 2006, 2603–2607; h) I.
Pravst, M. Zupan, S. Stavber, Tetrahedron Lett. 2006, 47,
4707–4710; i) A. Podgor{ek, S. Stavber, M. Zupan, J. Iskra,
Tetrahedron Lett. 2006, 47, 7245–7247; j) G. Stavber, M.
Zupan, S. Stavber, Tetrahedron Lett. 2006, 47, 8463–8466;
k) A. Podgor{ek, S. Stavber, M. Zupan, J. Iskra, Green
Chem. 2007, 9, 1212–1218.

but probably it suffices to read the review:

S. Stavber, M. Jereb, M. Zupan, Synthesis 2008, 1487–1513.

I requested this review in references.

[Edited on 21-2-2012 by Organikum]

Jeeez, louise! Messed up again!

For an account of how NOT to conduct an experiment continue reading:
A scale up of Synthesis 2006, 2603–2607 to 10 g HQDME (p-dimethoxybenzene) while reducing the relative amount of H2O was attempted. 10 g HQDME, 19 g I2, 400 ml H2O in 1 L flask. Heated to 50°C internal temp, added 8.5 g H2O2 30% and 0.5 ml H2SO4. Error 1: Underestimated hotplate, internal temp shot to 70°C, terrible sublimation of I2 everywhere. Obvious gas evolution (O2?) which quickly died down. Cooled to 50°C, stirred a few hours at 50°C. Still problems with I2 sublimation. The reaction was three-phased: large yellow top aqueous layer, very dark liquid bottom layer and solid I2. The stirring was deemed to be inadequate, since there was no thorough mixing of the phases. Error 2: From the looks of it (never judge a reaction based on what it looks like!), nothing had reacted and another 8.5 g H2O2 was added, after all even if it doesn't help, it will not hurt. Again: Gas evolution which quickly died away.

After ~27h, the reaction still looked the same and was extracted with DCM, washed in succession with bisulfite and water and the DCM removed under reduced pressure to obtain a yellow oil from which lots of snow white crystals precipitated, which were filtered off. From the filtrate precipitated more crystals which were filtered again. The crystals were supposed to be unreacted HQDME, but they certainly lacked the intense smell. So the oracle was consulted - and the somewhat unexpected answer was: clean 1,4-diiodo-2,5-dimethoxybenzene, amounting to 7% of theory.

The remaining oil was distilled under reduced pressure. A deep red forerun was discarded (free I2?). The minor residue imediately crystallized after removing heat and probably is the diiodine product. The distillate crystallized overnight to spectacular yellowish crystals with rock crystal like habit, just to melt over the course of the day. Again the oracle was consulted: iodo-HQDME, amounting to 50% of theory.

Total yield: 57%. The biggest losses probably occured during filtration of the dense oil.

Conclusion:
The procedure is kind of messy, with all the sublimating iodine. Furthermore the need of one mole of I2 is quite wasteful. But it does work. It also raises a few questions: the authors note that no diiodination occurs when increasing the amount of I2. Well, no wonder, given that H2O2 is needed for the reaction. Why didn't they try to increase the amount of H2O2 and couldn't the reaction actually be done with half a mole of I2 and by increasing the amount of H2O2? I feel I am missing something...

------

Fed up with the thing, another procedure was tried: "Mild and Efficient Iodination of Aromatic Compounds with Trichloroisocyanuric Acid/I2/Wet SiO2 System" Turk. J. Chem, 33 (2009), 67-72

Reaction is performed in DCM with TCCA on SiO2. Hopes were very low, after all heterogenous catalysis is way over the head of this chemist. And what the hell is wet SiO2 (50% w/w) supposed to mean? Silica gel was ground in a mortar (uff!) and mixed in a flask with an equivalent weight of H2O. This gave an unstirrable mess. The flask was placed in a warm place (ca. 30-35°C) for one week. Appearance didn't change, but the powder actually became nicely stirrable. The reaction was performed like in the paper scaled up to 10 g HQDME, with one exception, instead of "immediately" working it up, it was run over night, since the chemist was tired and even if it doesn't help, it will not hurt. The residue was a semi solid that was recrystallized to white plates, needles and blocks. Analysis revealed at least 1,4-dichloro-2,5-dimethoxybenzene, 1-iodo-4-chloro-2,5-dimethoxybenzene and 1,4-diiodo-2,5-dimethoxybenzene. Seriously, WTF? Overformylation, overiodination, overchlorination... Lately the overreactions are getting out of hand!

[Edited on 28-4-2012 by turd]

Quote: Originally posted by turd

Fed up with the thing, another procedure was tried: "Mild and Efficient Iodination of Aromatic Compounds with Trichloroisocyanuric Acid/I2/Wet SiO2 System" Turk. J. Chem, 33 (2009), 67-72 ... Analysis revealed at least 1,4-dichloro-2,5-dimethoxybenzene, 1-iodo-4-chloro-2,5-dimethoxybenzene and 1,4-diiodo-2,5-dimethoxybenzene. Seriously, WTF? Overformylation, overiodination, overchlorination... Lately the overreactions are getting out of hand!

Yes, I was also suspecting that if I hadn't added any SiO2 the result would have been exactly the same.

Do you think that it's worth trying the I2/H2O2 thing with 0.5 (or maybe 0.75) equivalents of I2 and double the H2O2?

After all, there was solid I2 during the whole reaction, so I don't see how it was necessary to add that much I2 - if there's a solid phase, then the liquid phases are saturated with I2.

The whole matter seems to be at least partly some kinetic thing. In http://acta.chem-soc.si/55/graph/acta-55%284%29-GA.htm they get 65% conversion with 0.5 mol I2 and 82% conversion with 1 mol I2 for 1,2-dimethoxybenzene. If 1 mol of I2 really was necessary, then they should only get 50% conversion in the first experiment.

With 3,4-dimethoxyacetophenone, they really get only half of the conversion with 0.5 mol I2. But that raises the question: What happens with the iodide, so that it cannot be regenerated by H2O2?

I still feel that I am missing something completely obvious.

PS: I don't see the point of powdering the I2 - at 50°C there is appreciable sublimation and growth of nice I2 crystals.