Org Prep Daily

July 3, 2007

8-iodo-4,7-octadiynoic acid methyl ester

Filed under: Chris Douglas, procedures — milkshake @ 12:58 am

iodoacetylene1.gif

Silver nitrate (0.74 g, 4.40 mmol) was added to a solution of methyl 4,7-octadiynoate (6.77 g, 44.0 mmol) in THF (45 mL).  The suspension was shielded from light and stirred at rt for 5 min.  N-iodosuccinimide (10.1 g, 44.0 mmol) was added to the reaction mixture in one portion and stirring was maintained for 2h.   The reaction mixture was poured into 100 mL water and extracted with Et2O (3´100 mL).  The combined extracts were dried with Na2SO4 and concentrated onto Celite (20 g).  Purification of the resulting powder by flash chromatography (1:10 Et2O:Pentane) gave the title compound as a light and air sensitive colorless powder, 8.52 g (30.4 mmol, 69%).

1H NMR (500 MHz, CDCl3) d 3.70 (s, 3H), 3.30 (t, J = 2.2, 2H), 2.52–2.48 (m, 4H); 13C NMR (125 MHz, CDCl3) d 172.4, 87.9, 79.5, 73.8, 51.8, 33.2, 14.6, 11.8, –4.6; IR (film) 2997, 2950, 1730 cm-1 LRMS (CI, NH4) m/z, 294 (M + NH4)+, 277 (M + H)+, 168.  Calcd for C9H9IO2: C, 39.16; H, 3.29. Found C, 39.37; H, 3.34.

Note: 1-Iodo-phenylacetylene can be easily prepared using the same procedure. The yields can be slightly variable depending on the scale.

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15 Comments »

  1. variable as in upwards? i’ve done analogous brominations of an alkyne with AgOAc/NBS – yields never below 80% (and from memory usually >90%), one of my favourite easy reactions. but always on a smaller scale than this, or maybe the nitrate counterion is a bit oxidising?

    Comment by kiwi — July 3, 2007 @ 3:12 am

  2. These things are not exceedingly stable, they are highly endothermic. I have seen self-combustion of neat 1-iodopropyne.

    Comment by milkshake — July 3, 2007 @ 3:20 am

  3. sweet i didn’t know that, i had heard about Cu and Ag acetylides getting nasty though.

    Comment by kiwi — July 3, 2007 @ 4:00 am

  4. Are those alkynyl iodide as unstable as alkyl and alkenyl iodide? (My guess is that they would be even less stable)

    Could it help to add copper wires to stabilize your products and increase your yields?

    Comment by Spiro — July 3, 2007 @ 8:45 am

  5. kiwi – the yields were variable in the range of low 60s to low 80s – this was the largest scale the rxn was run on.

    spiro – to add copper to the product and get a stabilizing effect, I’d probably have needed to keep it as a solution – the product is a solid after all. also, since the next step was a double hydroboration with (sia)2BH, I would be concerned that trace copper salts might promote side rxns like iodide reduction. the next step was bad enough already with yields usually south of 50%. these alkynyl iodides and bromides are unstable. this one was stored shielded from light, under N2 in a -20 C freezer. these conditions (and related ones like the AgOAc mentioned by kiwi) are really mild though – the weak, doubly propargylic methylene did not appear to react.

    iodo and bromo alkynes can be lacrimators and sensitizers in addition to explosive – handle these fellows with care.

    Comment by cjdquest — July 3, 2007 @ 9:28 am

  6. I was not just talking about storing your product on copper, but adding copper during every single operation you do during your synthesis : adding copper to the reactor, then to the celite, then to the Na2SO4, then to your silica, then to your final flask, and storing your compound in the solvent used in the hydroboration step… over copper.

    I used to work with alkyl iodide and adding copper everywhere allowed me to be very careless. A friend of mine who worked with allyl iodides (you can imagine the stability!!!) taught me those tricks.

    I understand your fear of having trace amounts of copper that would catalyze side-reactions, but if you fish your wires out before starting the next step, you should be fine. After all, metallic copper should not dissolve in organic solvents – ppm, ppb?.

    Comment by spiro — July 3, 2007 @ 10:16 am

  7. spiro – ah – i see. although what you suggestion seems logical, I would, unfortunately, expect an inorganic reaction between the Ag (I) ion and Cu (s) to give Ag (s) and Cu (II). This redox reaction happens readily between Ag(I) aq and Cu metal and could just as well go in THF to kill the catalyst. It might be worth trying out though, since the iodination might be done before the catalyst is decomposed.

    http://www.chemicool.com/definition/redox_reactions_introduction.html

    As for storing over Cu, although metallic Cu would not be in the organic solvent beyond the level you suggest, the expected product of attack on the stabilizer (CuI) certainly would. This is what I’d be more concerned about. I did hear an antidote about a student “discovering” an unprecedented selectivity for conjugate addition from Grignards without the addition of Cu salts. The PI got very excited until student 2 could not reproduce the original result. – the difference maker? Student 1 stored his bromides over Cu before generating the Grignard, while student 2 distilled them prior to use…

    Comment by cjdquest — July 3, 2007 @ 10:48 am

  8. OK! Cu is probably a looser in this reaction. You have the point ;-)

    However I maintain that the amount of Cu leaking, either as Cu metal or Cu+ or Cu(n+) should be very low during the storage – because the degradation of these iodides is certainly autocatalytic, which means that if you add an inhibitor, there should be no degradation at all.

    From my experience, when I concentrate the purified iodides after I have columned them, they turn pink, then red, then dark, etc… It is a matter of seconds or minutes. However when I add one tiny chunk of Cu and hexanes as a solvent, I can leave my flask before the window for hours without noticing anything, and the Cu wire remains clean.

    Comment by Spiro — July 3, 2007 @ 2:15 pm

  9. I’ve often wondered why MeI often comes stored over Cu shot; so CuI is the actual stabilizer, keeping free I- from cooking the whole lot?

    Comment by Jose — July 3, 2007 @ 4:15 pm

  10. Cu gobbles up I2. It keeps your MeI colorless but the produced CuI slowly precipitates in the bottle – so you should not shake the bottle with MeI needlesly as the cloudy MeI can take some time to settle…
    I was doing a large-scale methylations where CuI was undesirable. Instead of using the ridiculously overpriced 99.5%+ methyl iodide, I bought the common cheap grade with lots of CuI sediment and I filtered it through a short pad of neutral activated alumina, then I added some fresh (sandpaper-cleaned) Cu wire to the filtered stuff and kept it in dark, at RT.
    I don’t recommend adding Cu to stabilize iodoalkynes – in fact I would worry the copper effect could be rather opposite with the triple bond compounds.

    Comment by milkshake — July 3, 2007 @ 4:42 pm

  11. thanks for clearing up my poorly worded post, milkshake. I did mean attack of I2 on the stabilizer Cu (s) produces the expected product CuI, but rereading my post I see that what I wrote might be misunderstood as the stabilizer being CuI – sorry for any confusion.

    Comment by cjdquest — July 4, 2007 @ 5:39 pm

  12. That’s not N-iodosuccinimide you have drawn. :)

    See: http://blog.chembark.com/2007/07/04/mistakes-and-mnemonics/

    Comment by Chemgeek — July 5, 2007 @ 10:06 pm

  13. Milkshake, new post pls.

    Comment by dan — July 16, 2007 @ 7:46 pm

  14. Can’t. Chemistry does not work. And what works cannot be published,

    Comment by milkshake — July 16, 2007 @ 8:01 pm

  15. Milkshake: “What I cannot create I cannot understand”

    Comment by Wavefunction — July 20, 2007 @ 2:18 pm


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