Org Prep Daily

May 16, 2007

5-chlorofuroic acid

Filed under: procedures — milkshake @ 4:37 am

chlorite.gif 

A solution of 5-chlorofurfural 823 mg (6.305 mmol) in acetonitrile 25 mL was diluted with water 150mL and sulfamic acid 1.50g (15.4 mmol) was added. After complete dissolution, NaClO2 1.58g (80% tech product, Aldrich, 14mmol) solid was added in one portion and the mixture was stirred for 30 min at RT. (HPLC indicated complete a conversion within 10 min). The obtained golden-yellow reaction mixture (containing some dissolved Cl2 and ClO2) was extracted twice with ethyl acetate (2x100mL). The organic extracts were washed with water (100mL), combined, dried with magnesium sulfate and evaporated. The obtained crystalline residue was dissolved in acetonitrile (30mL, with gentle heating) and re-evaporated to dryness. Dried on highvac.
Y= 893 mg (96.5%) of a pearl-shiny white crystalline solid.

1H(d6-DMSO, 400MHz): 13,376(br s, 1H), 7.291(d, 3.6Hz, 1H), 6.702(d, 3.6Hz, 1H)
13C(d-DMSO, 100MHz): 158.26, 144.59, 139.10, 120.00, 109.63; LC-MS(-ESI): 145, 147 (M-1)

More sensitive substrates are often oxidized in presence of chlorine scavenger (isobutylene, etc). The chlorite + sulfamic acid in aqueous acetone allowed clean oxidation with unprotected phenolic aldehyde-arylacetone substrate: J. Chem. Soc. Perkin 1, (1980), 136-140

11 Comments »

  1. “More sensitive substrates are often oxidized in presence of chlorine scavenger (isobutylene, etc).”

    Is sulfamic acid not supposed to be a chlorine scavenger?

    Comment by Spiro — May 16, 2007 @ 9:01 pm

  2. if it is, then it certainly does not work according to the plan. The produced reaction mix is golden-yellow, from some volatile yellow stuff that goes into rotavap. Cl2 or ClO2, IMHO.
    I think sulfamic acid is there just to buffer the reaction.

    Comment by milkshake — May 17, 2007 @ 1:34 am

  3. Nice transformation. Is chlorine cleavage the main (less than 3% i guess) by-product?

    Comment by Organic Chemistry Help — May 17, 2007 @ 7:38 am

  4. there is no observable sideproduct, it goes cleanly peak-to-peak on HPLC, practically instant.
    It is easy to lose 4% on aqueous workup and on highvac. These furoic acids are quite water-soluble and also somewhat volatile.

    Comment by milkshake — May 17, 2007 @ 10:22 am

  5. At first sight, I also thought it was a buffer, but it is too fancy for a
    buffer.

    Here they confirm it is a scavenger for the hypochlorite species:
    http://doi.wiley.com/10.1002/anie.200700159 ref 14

    Comment by Spiro — May 17, 2007 @ 8:43 pm

  6. hey milkshake, have you ever used something similar to go all the way up to the acid from the primary alcohol? i’ve seen it done with NaClO2/NaOCl/TEMPO, but the reaction i’m thinking of (propargyl alcohol -> propynoic acid) dies under these conditions (the product is sensitive to the NaOCl). i’ve been using the jones reagent to do this, it works, but i die a little inside every time.

    Comment by kiwi — May 17, 2007 @ 9:40 pm

  7. There were two papers from Merck process group on catalytic oxidation of alcohols to carboxylic acids, from early 2000. One used H5IO6 and catalytic CrO3 in wet acetonitrile and the other one was TEMPO radical + NaClO2 + catalytic bleach. I tried the H5IO6 + cat. CrO3 on 5-chlorofurfural first, because previously I had good luck with using this “catalytic Jones” on sensitive substrates – but it did not work so great in this particular case.

    Comment by milkshake — May 18, 2007 @ 4:31 am

  8. i have seen the paper where it was catalytic in bleach, but decided that still might not be mild enough (a patent i saw also had a few words to that effect, but i’m quite sceptical of patents). i haven’t tried it yet though. and i’ll certainly have a look at that catalytic jones, thanks

    Comment by kiwi — May 20, 2007 @ 6:52 am

  9. There is a new book “Oxidation of Primary Alcohols to Carboxylic Acids
    A Guide to Current Common Practice”. Springer 2006
    http://www.springer.com/dal/home/chemistry/organic?SGWID=1-142-22-173663739-detailsPage=ppmmedia|samplePages

    by the way, they have a free chapter about TEMPO-mediated oxidation:
    http://www.springer.com/cda/content/document/cda_downloaddocument/9780387354316-c6.pdf?SGWID=0-0-45-346628-p173663739

    Comment by Alexey — May 20, 2007 @ 11:23 am

  10. Dear MS,

    I am trying to convert 2,5 dimethoxy furan derivative into the corressponding butryo lactone derivative (3-bromofuran-2(5H)-one) using 48 % aq HBr in acetone but that gave low yield (20 -30% yield) i am unable to conclude about the low yield . As per the literature, i used high excess of (30 v) of 48 % aq. HBr and acetone as solvent.

    I am gettig one non ploar spot in the TLC. isolation of this compound also problematic with distillation results in low receovery. Could you suggest me any conditions for this convesion.

    Thanks

    Marto

    Comment by marto — November 24, 2013 @ 1:36 pm

    • sorry I am not familiar with this procedure, and in the absence of more information I cannot give you a qualified answer. (My first instinct is that a ring opening reaction of alkoxyfurane with HBr in acetone is bound to produce a nasty polymeric mess.)

      Comment by milkshake — November 24, 2013 @ 4:44 pm


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