Organic Syntheses, Coll. Vol. 10, p.696; Vol. 77, p.141
THE DESS-MARTIN PERIODINANE:
[ 1,2-Benziodoxol-3(1H)-one, 1,1,1-tris(acetyloxy)-1,1-dihydro- ]
Submitted by Robert K. Boeckman, Jr., Pengcheng Shao, and Joseph J.
Checked by Kevin P. Minbiole and Amos B. Smith, III.
Caution: Compounds 1 and 2 are heat- and shock-sensitive compounds,
showing exotherms when heated (>130?C). All operations should be conducted behind an explosion shield.
A. 1-Hydroxy-1,2-benziodoxol-3(1H)-one 1-oxide (1) . A 2-L, three-necked,
round-bottomed flask, fitted with a mechanical stirrer, condenser, and an immersion thermometer is charged with 80.0 g (0.48 mol) of potassium
bromate (KBrO) and 750 mL of 2.0 M sulfuric acid (Note 1),(Note 2),(Note 3). 3
The resulting clear solution is heated to 60?C in an oil bath and 80.0 g of finely powdered 2-iodobenzoic acid (0.323 mol) is added in 10-g portions over 40
min (Note 4), (Note 5). The solution becomes red-orange, bromine vapor is
evolved, and a white solid begins to separate (Note 6). After the addition is
complete, the temperature is maintained at an internal temperature of 65?C for 2.5 hr (Note 3).
The reaction mixture is cooled to 2-3?C in an ice-water bath, and the resulting solids are collected by vacuum filtration (Note 7), (Note 8). The filter
cake is thoroughly washed successively with 500 mL of cold deionized water, 2 × 80 mL of absolute ethanol , and 500 mL of cold deionized water affording 88.2 g (98% of theoretical) of moist solid iodinane oxide 1 (Note 9), (Note 10).
B. 1,1,1-Triacetoxy-1,1-dihydro-1,2-benziodoxol-3(1H)-one (2) . A 1-L,
three-necked, round-bottomed flask, equipped for magnetic stirring and fitted with an immersion thermometer, is charged with 88.2 g of the moist solid iodinane oxide 1 , 150 mL of glacial acetic acid , and 300 mL of acetic anhydride
(Note 11). The flask is flushed with dry argon, and maintained under a dry argon
atmosphere. Magnetic stirring is commenced, and the mixture is heated to 85?C (internal temperature) over 30 min by means of an oil bath, and kept at this
temperature until all the solids dissolve (20 min) to afford a colorless to clear
yellow solution (Note 12). Heating and stirring are discontinued and the reaction mixture is allowed to cool slowly to room temperature in the oil bath for 24 hr. A large quantity of colorless crystals separate during this time (Note 13). The
resulting crystalline solids are isolated by careful vacuum filtration in the reaction vessel under argon using a fritted adapter followed by washing the solids with three 80-mL portions of anhydrous ether and subsequent vacuum
filtration in the reaction vessel as above (Note 14), (Note 15). Residual solvent
is removed under vacuum affording 101.0 g (74% yield over 2 steps) of periodinane 2 as a white, free-flowing crystalline solid that is largely or completely soluble (slightly cloudy to clear solution) in chloroform and
methylene chloride and is sufficiently pure (95%) to be suitable for use in
oxidations (Note 16),(Note 17),(Note 18),(Note 19).
1. Although no problems with explosion of 1 or 2 have been encountered in
the use of this procedure, prudence dictates that all operations should be
2,34567,8conducted behind an explosion shield.
Potassium bromate (>99.5%) was used as received from Fluka Chemical 2.
3. Use of higher concentration sulfuric acid (2.0 M) than traditionally
2-iodobenzoic acid to employed is crucial to allow complete conversion of the
21. In the submitters hands, use of lower concentrations (0.5 M) of sulfuric
acid at 60?C led to exclusive formation of
1-hydroxy-1,2-benziodoxol-3(1H)-one. When lower concentrations of sulfuric
acid are employed, higher temperatures are required to effect oxidation, as judged by the initiation of bromine evolution. One of the factors leading to the lack of reproducibility in the preparation of 2 results from incomplete conversion
4. 2-Iodobenzoic acid (Aldrich Chemical Company, Inc.) was recrystallized from toluene (100 g/500 mL).
5. The bromine vapors are vented by inverting a funnel over the open condenser (allowing a small gap between the funnel and the condenser top) with the stem attached to a gas washing bottle containing saturated aqueous sodium thiosulfate solution, which is in turn, connected to a water aspirator.
6. Addition of the 2-iodobenzoic acid to the bromate-aqueous acid mixture
results in an easily controlled, smooth reaction and an easily stirred reaction mixture. The stirring rate should be regulated such that splashing is minimized and solids do not accumulate on the walls or roof of the reaction vessel. Any solids which adhere to the sides or roof of the reaction vessel above the level of the liquid should be washed back into the reaction mixture with the minimum amount of 2M sulfuric acid. Addition of the bromate to the mixture of
2iodobenzoic acid and sulfuric acid as originally described, led to a thick
precipitate that was difficult to stir, and the accumulation of solid on the walls of
the reaction vessel. Given the thermal sensitivity of 1, the present procedure
8,9appears much safer (Note 1).
7. The reaction mixture is thoroughly cooled prior to filtration and cold water is employed for washing because of the low but appreciable solubility of 1 in
0.3 g/100 mL). water (
8. Use of a ceramic Büchner funnel with coarse filter paper is recommended to avoid scraping a glass frit during removal of 1. A rubber spatula is
recommended for stirring and manipulation of the filter cake. The filter cake can be conveniently removed from the funnel by applying a small amount of air pressure to the stem.
9. All washes were conducted by slurrying the solids on the filter bed with a rubber spatula followed by application of the vacuum. In view of the sensitivity
34567(Note 10) of this intermediate and/or the periodinane 2, care should be
taken to avoid thorough drying of the solid oxide 1. The use of the ethanol
washes appears essential to reduce further the explosion hazard. These washes presumably destroy any unreacted bromate present in the solids. The submitters have observed that another of the factors leading to the lack of reproducibility in the preparation of the periodinane is associated with the
ethanol after the washing in an effort to avoid drying the incomplete removal of
oxide 1. The presence of ethanol in the oxide results in destruction of the
periodinane 2 as it is formed in the next transformation. The use of a final aqueous wash serves to remove the ethanol and keep the oxide moist. This
moisture is not detrimental in the next reaction. Small samples of moist solid 1
were also washed successively with reagent grade acetone and anhydrous ether,
and residual solvent was removed under vacuum. Identical overall yields of 2
were obtained by both procedures.
19110. Recently, the H NMR of 1 in d DMSO has been reported. The H NMR 61spectrum of 1 prepared as described above was identical to that reported: H
NMR (400 MHz in d DMSO) δ as follows: 7.84 (t, 1 H, J = 14.8), 7.99 (t, 1 H, J 6
= 7.9), 8.02 (d, 1 H, J = 14.8), 8.15 (d, 1 H, J = 7.9) . Incomplete conversion results in impurity peaks at δ 7.71 (t or m, 1 H) from
1-hydroxy-1,2-benziodoxol-3(1H)-one or from both
1-hydroxy-1,2-benziodoxol-3(1H)-one and 2-iodobenzoic acid (if both are
present), and δ 7.48 (t, 1 H) and 7.25 (t, 1 H) from 2-iodobenzoic acid (if
present). Conversion to 1 can also be conveniently assayed by reduction of a weighed sample of 1 with excess aqueous sodium iodide and titration of the
resulting iodine with standardized 1N sodium thiosulfate solution to a colorless
endpoint (1 mmol of thiosulfate per mmol of 1 required). The physical
properties of authentic 1 are also diagnostic. From the present procedure, 1 is
obtained as a somewhat granular, easily-filtered solid.
1-Hydroxy-1,2-benziodoxol-3(1H)-one or impure samples of 1 containing
significant amounts of 1-hydroxy-1,2-benziodoxol-3(1H)-one and possibly 2-iodobenzoic acid are obtained as sticky precipitates which are difficult to filter and wash, and which retain substantial amounts of solvent. Samples of the
moist oxide 1 were found to exhibit impact sensitivity and were found to exhibit exotherms upon heating (> 130?C) characteristic of an explosive material upon examination by differential scanning
11. Glacial acetic acid and acetic anhydride were used as received from J. T.
Baker Chemical Co. The checkers used glacial acetic acid as received from
Fisher Scientific and acetic anhydride (99%) as received from Aldrich Chemical
12. Monitoring the reaction by NMR immediately upon dissolution of 1
indicated that the major product was the desired 2 accompanied by a minor
amount of what is likely the I(V) monoacetate and a small amount (<5%) of
1-acetoxy-1,2-benziodoxol-3(1H)-one possibly resulting from incomplete oxidation to 1 (see (Note 17) for chemical shift values). Heating the reaction mixture for 3 hr at 110?C results in complete conversion to
1-acetoxy-1,2-benziodoxol-3(1H)-one; thus prolonged heating should be avoided.
13. Slow cooling affords better product crystallinity and easier handling during isolation of 2.
Ether was dried and deoxygenated by distillation from sodium 14.
benzophenone ketyl under nitrogen just prior to use. Experience has shown that the quality of reagent 2 is most directly affected by 1) failure to control conversion to the triacetate and 2) exposure to moisture during filtration and other manipulations performed during isolation of the periodinane. Extensive hydrolysis of 2 was observed when washing with ether was conducted in a
15. Vacuum filtration was accomplished with a water aspirator fitted with a drying tube. A gas inlet tube with a Teflon stopcock and a medium to coarse porosity glass fritted disc sealed in the bottom of the joint was employed for filtration in the flask. The outlet of the fritted adapter is connected to a filter flask that is attached to a water aspirator, and argon is introduced to equalize
pressure in the flask during filtration. The fritted outlet adapter can be purchased from Ace Glass Co., Vineland, NJ (Cat. No. 5295-16-SP). The checkers used a similar adapter from United Glass Technologies. A glove bag or Schlenk filtration is also suitable to effect filtration under an inert atmosphere when the humidity is high.
16. The submitters reported a two-step yield of 111.0 g (80%).
17. The purity of the Dess-Martin periodinane (2) was assayed by treatment
of 2 (1 equiv) with an excess of benzyl alcohol (2 equiv) in methylene chloride
(CHCl) followed by analysis of the reaction mixture for benzaldehyde by 22
capillary vapor phase chromatography (15-m fused silica capillary column, Durawax DX3 stationary phase, 120?C). After correction for response factors, the purity was established to be ?95%.
118. The Dess-Martin periodinane (2) had H NMR (300 MHz in CDCl) δ as 3
follows: 1.99 (s, 6 H), 2.32 (s, 3 H), 7.91 (t, 1 H, J = 7.4), 8.09 (t, 1 H, J = 8.1), 8.29 (d, 2 H, J = 8.1) . Minor impurity peaks were observed at δ 8.39 (d), 8.21
13(d), 8.00 (d), 7.27 (s), and 2.08 (s) (possibly the mono acetate); dC NMR (75
MHz in CDCl) δ: 20.2, 20.4, 125.9, 126.5, 131.7, 133.8, 135.8, 142.2, 166.1, 3
174.0, 175.7 . The checkers note that a freshly opened bottle of deuterochloroform (CDCl ) was required to dissolve 2 and that drying of older 3
CDCl by running the solvent through potassium carbonate (KCO) did not 323
facilitate dissolution. The submitters observed the same phenomenon and believe that traces of acid in the fresh CDCl may be responsible for this 3
19. The Dess-Martin periodinane (2) can be stored in a dark bottle under
argon at ?20?C in a freezer.
Waste Disposal Information
All toxic materials were disposed of in accordance with "Prudent Practices in the Laboratory"; National Academy Press; Washington, DC, 1995.
The Dess-Martin periodinane
[1,1,1-triacetoxy-1,1-dihydro-1,2-benziodoxol-3(1H)-one (2)] is one of
several 12-I-5 periodinane species developed by J. C. Martin and co-workers, and has found wide acceptance and utility for the selective oxidation of primary
2,10and secondary alcohols to carbonyl compounds. The present procedure is a
2variation of the Martin procedure and is based heavily upon it. Modified
1112preparations have been reported by Ireland and Schreiber. The reported
34567explosiveness of samples of impure 2 has prompted a more thorough
2examination of the properties of 2. Possible impurities that could be
responsible for rendering the samples explosive are 1 and/or the monoacetate
derivatives of 1 and 2 that could arise by incomplete oxidation to 1 or hydrolysis
of 2 on storage. Samples of 2 that indicate the presence of significant quantities
1of 1 or the monoacetate derivatives of 1 and 2 as judged by H NMR should be
handled with caution. Although these investigations were inconclusive as to the precise nature of the impurity/ies that rendered the impure samples of 2
explosive, fresh samples of crude moist 1 were found to be both impact and heat sensitive, decomposing explosively under confinement. Pure 2 is significantly less temperature and impact sensitive; nevertheless, it should be handled with appropriate caution as a potentially explosive
The Dess-Martin periodinane (2) has found wide utility as a selective oxidant in sensitive, highly functionalized intermediates commonly encountered in the
2synthesis of natural products and related complex molecules. The Dess-Martin
periodinane (2) has several advantages over other commonly employed
oxidizing agents such as chromium(VI)-based reagents and dimethyl sulfoxide
(DMSO)-based oxidations including nearly ideal stoichiometry, mild non-acidic or mildly acidic reaction conditions, shorter reaction times, relative ease in the preparation and storage of the reagent, simplified workups with easy removal of the by-products of oxidation, the ease of safe disposal of residues, and the lower toxicity of the the reagents and by-products [relative to chromium(VI) reagents
A selection of cases in which 2 has been found to be particularly efficacious is
19given in the Table. Additional examples are cited in references and .
Particularly noteworthy examples include the oxidation of acid- and base-sensitive systems, systems containing sulfur and selenium, and 1,3-diols
to 1,3-dicarbonyl compounds. Use of chromium reagents in these latter cases
often leads to fragmentation products.
References and Notes
1. Department of Chemistry, University of Rochester, Rochester, New York
2. Dess, D. B.; Martin, J. C. J. Am. Chem. Soc. 1991, 113, 7277.
3. Plumb, J. B.; Harper, D. J. Chem. Eng. News 1990 (July 16) 3;
4. Hartmann, C.; Meyer, V. Chem. Ber. 1893, 26, 1727;
5. Greenbaum, F. R. Am. J. Pharm. 1936, 108, 17;
6. Banerjee, A.; Banerjee, G. C.; Dutt, S.; Banerjee, S.; Samaddar, H. J.
Indian Chem. Soc. 1980, 57, 640;
7. Banerjee, A.; Banerjee, G. C.; Bhattacharya, S.; Banerjee, S.; Samaddar,
H. J. Indian Chem. Soc. 1981, 58, 605.
8. Differential scanning calorimetry and impact studies on 1 and 2 were
performed by the courtesy of Dr. David Coffen and his colleagues of
Hoffmann La-Roche Inc., and Dr. Ichiro Shinkai and his colleagues of
Merck Co. Both moist and partially dried samples of 1 were found to
exhibit impact sensitivity and large exotherms characteristic of
potentially explosive deflagration were observed beginning at
temperatures above 140?C. Samples of pure 2 appeared somewhat less
impact sensitive, and had smaller exotherms beginning at 170?C, but
prudence dictates that 2 be handled with appropriate precautions as
9. Recently, an alternative preparation of 1 employing oxone as the oxidant
has been reported: Frigerio, M.; Santagostino, M.; Sputore, S. J. Org.
Chem. 1999, 64, 4537
10. For a leading reference, Boeckman, R. J. In "Encyclopedia of Reagents
for Organic Synthesis"; Paquette, L. A., Ed.; Wiley: Chichester, U.K.,
1995, Vol. 7, pp. 4982-4987.
11. Ireland, R. E.; Liu, L. J. Org. Chem. 1993, 58, 2899;
12. Meyer, S. D.; Schreiber, S. L. J. Org. Chem. 1994, 59, 7549.
13. Ladlow, M.; Pattenden, G.; Teague, S. J. Tetrahedron Lett. 1986, 27,
14. Farr, R. A.; Peet, N. P.; Kang, M. S. Tetrahedron Lett. 1990, 31, 7109. 15. de Lera, A. R.; Okamura, W. H. Tetrahedron Lett. 1987, 28, 2921. 16. Hanson, G. J.; Lindberg, T. J. Org. Chem. 1985, 50, 5399. 17. Polson, G.; Dittmer D. C. J. Org. Chem. 1988, 53, 791. 18. Linderman, R. J.; Graves, D. M. J. Org. Chem. 1989, 54, 661. 19. Danishefsky, S. J.; Mantlo, N. B.; Yamashita, D. S.; Schulte, G. J. Am.
Chem. Soc. 1988, 110, 6890.
20. Abelman, M. M.; Overman, L. E.; Tran, V. D. J. Am. Chem. Soc. 1990,