Selenium(IV) Oxide


[7446-08-4]  · O2Se  · Selenium(IV) Oxide  · (MW 110.96)

(oxidant of activated, saturated positions)

Alternate Name: selenium dioxide.

Physical Data: mp 315 °C (subl); d 3.95 g cm-3.

Solubility: sol water, methanol, ethanol, acetone, acetic acid.

Form Supplied in: off-white powder;1 widely available.

Purification: by sublimation, or by treatment with HNO3.28

Handling, Storage, and Precautions: toxic; corrosive; causes intense local irritation of skin and eyes; use in a fume hood.

Allylic Hydroxylation.

Selenium(IV) oxide is known primarily for hydroxylation of activated carbon-bearing positions, particularly at allylic (or propargylic) sites. Studies by Guillemonat and others have led to the following hydroxylation selectivity rules:2,3

  • 1)Hydroxylation occurs a to the more substituted end of the double bond.
  • 2)The order of facility of oxidation is CH2 > CH3 > CH.
  • 3)When the double bond is in a ring, oxidation occurs within the ring when possible, and a to the more substituted end of the double bond.
  • 4)Oxidation of a terminal double bond affords a primary alcohol with allylic migration of the double bond.

    An example of rules (1) and (2) is shown in the oxidation of 3-methyl-3-butene, where the allylic methylene position is oxidized in preference to the methyl or methine positions (eq 1).2 Alkene-selective oxidation of 5,6-dihydroergosterol in ethanol, an example of rule (3), occurs at C-14 and is followed by allylic rearrangement to give a 7a-ethoxy product (eq 2).4 The mechanism of the allylic oxidation reaction is proposed to be initiated by ene addition, followed by dehydration and [2,3]-sigmatropic rearrangement of the resultant allylseleninic acid.5,6 In a key step of the synthesis of a-onocerin, a-oxidation in acetic acid leads to an unsaturated g-lactone product in good yield (eq 3).7 The milbemycins have been hydroxylated in the 13b-position by selenium dioxide.8 Because selenium dioxide forms selenious acid (H2SeO3) in the presence of water, hydroxylations of alkenes containing acid-labile groups (e.g. acetals) have been run in pyridine.9

    Higher-Order Oxidations.

    Selenium dioxide can introduce carbonyl functionality at activated positions, and can also effect dehydrogenation10-13 at highly activated saturated sites. For instance, phenylglyoxal is isolated in high yield from a-oxidation of acetophenone (eq 4).14 On a large scale, dissolution of the selenium dioxide in aqueous dioxane at 55 °C is required prior to acetophenone addition. Similarly, 6-methyluracil is readily converted to orotaldehyde in acetic acid (eq 5).15 Oxidation of aryl-substituted succinic acids to maleic anhydride analogs occurs readily in acetic anhydride (eq 6).16 This is a preferred method, since oxidations of this type with N-Bromosuccinimide give bromoarene byproducts. Additionally, selenium dioxide in the presence of Trimethylsilyl Polyphosphate has been used to aromatize cyclohexenes and cyclohexadienes.17 Using only a slight excess (1.2 molar equiv) of selenium dioxide in pyridine, methyl 2-methyl-4-pyrimidinecarboxylate has been prepared regioselectively from 2,4-dimethylpyrimidine after methanolysis of the carboxylic acid product (eq 7).18 Interestingly, Sulfuric Acid-catalyzed oxidation of 1-octene in acetic acid affords a 1,2-diacetate product (eq 8).19 Only a trace amount of 1-acetoxy-3-octene is observed.

    Oxidative Cleavage.

    Attack of selenium dioxide at activated positions can lead to oxidative bond cleavage when appropriate leaving groups are present. Aryl propargyl ethers undergo oxidation at the a-alkynyl position to afford a phenolic species and propargyl aldehyde (eq 9).20 The analogous aryl allyl ether fragmentations occur in somewhat lower yields. (Hydroxyaryl)pyrazolines have been oxidized, with nitrogen extrusion, to afford 2-hydroxychalcone products (eq 10).21 Oxidations of pyrazolines with Bromine, Potassium Permanganate, Chromium(VI) Oxide, and other reagents result in pyrazole formation.

    Miscellaneous Transformations.

    Alkyl and aryl nitriles can be prepared from the corresponding aldehydes via conversion to the aldoxime, followed by catalytic selenium dioxide-mediated elimination (eq 11).22,23 Aliphatic nitriles are formed at rt, while aryl nitrile formation requires heating. 1,2,3-Selenadiazoles have been synthesized by treatment of an N-benzylazepine 4-semicarbazone with selenium dioxide (or selenoyl dichloride) (eq 12).24,25 The N-benzyl proximal product is formed with high regioselectivity vis-à-vis the distal product in polar solvents. Nonpolar solvents give ca. 3:1 mixtures (proximal/distal). The oxygen-catalyzed reaction of trialkylboranes with 1 equiv of selenium dioxide affords a dialkyl selenide as the major product.26 Similarly, dialkyl selenides have been prepared by reaction of alkyllithiums or Grignard reagents with selenium dioxide.27

    Related Reagents.

    Selenium(IV) Oxide-t-Butyl Hydroperoxide.

    1. Stahl, K.; Legros, J. P.; Galy, J. Z. Kristallogr. 1992, 202, 99.
    2. (a) Guillemonat, A. AC(R) 1939, 11, 143. (b) Fieser, L. F.; Fieser, M. FF 1967, 1, 992.
    3. Bhalerao, U. T.; Rapaport, H. JACS 1971, 93, 4835.
    4. Fieser, L. F.; Ourisson, G. JACS 1953, 75, 4404.
    5. Arigoni, D.; Vasella, A.; Sharpless, K. B.; Jensen, H. P. JACS 1973, 95, 7917.
    6. Wiberg, K. B.; Nielsen, S. D. JOC 1964, 29, 3353.
    7. Danieli, N.; Mazur, Y.; Sondheimer, F. TL 1961, 310.
    8. Tsukamoto, Y.; Sato, K.; Kinoto, T.; Yanai, T. BCJ 1992, 65, 3300.
    9. Camps, F.; Coll, J.; Parente, A. S 1978, 215.
    10. Bernstein, S.; Littell, R. JACS 1960, 82, 1235.
    11. Heller, M.; Bernstein, S. JOC 1961, 26, 3876.
    12. Fried, J. H.; Arth, G. E.; Sarett, L. H. JACS 1959, 81, 1235.
    13. Allen, G. R.; Austin, N. A. JOC 1961, 26, 4574.
    14. Riley, H. A.; Gray, A. R. OSC 1943, 2, 509.
    15. Zee-Cheng, K.-Y.; Cheng, C. C. JHC 1967, 4, 163.
    16. Hill, R. K. JOC 1961, 26, 4745.
    17. Lee, J. G.; Kim, K. C. TL 1992, 33, 6363.
    18. Sakasai, T.; Sakamoto, T.; Yamanaka, H. H 1979, 13, 235.
    19. Javaid, K. A.; Sonoda, N.; Tsutsumi, S. TL 1969, 4439.
    20. Kariyone, K.; Yazawa, H. TL 1970, 2885.
    21. Berge, D. D.; Kale, A. V. CI(L) 1979, 662.
    22. Sosnovsky, G.; Krogh, J. A. S 1978, 703.
    23. Sosnovsky, G.; Krogh, J. A.; Umhoefer, S. G. S 1979, 722.
    24. Maryanoff, B. E.; Rebarchak, M. C. JOC 1991, 56, 5203.
    25. Meier, H.; Voigt, E. T 1972, 187.
    26. Arase, A.; Masuda, Y. CL 1975, 419.
    27. Arase, A.; Masuda, Y. CL 1975, 1331.
    28. Perrin, D. D.; Armarego, W. L. F. Purification of Laboratory Chemicals, 3rd ed.; Pergamon: New York, 1988; p 342.

    William J. Hoekstra

    The R. W. Johnson Pharmaceutical Research Institute, Spring House, PA, USA

    Copyright 1995-2000 by John Wiley & Sons, Ltd. All rights reserved.