Org. Synth. 2000, 77, 141
DOI: 10.15227/orgsyn.077.0141
THE DESS-MARTIN PERIODINANE: 1,1,1-TRIACETOXY-1,1-DIHYDRO-1,2-BENZIODOXOL-3(1H)-ONE
[
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. Mullins
1
.
Checked by Kevin P. Minbiole and Amos B. Smith, III.
1. Procedure
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 (KBrO3) and
750 mL of 2.0 M sulfuric acid
(Note 1),(Note 2),(Note 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).
2. Notes
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 conducted behind an explosion shield.
2,3
4
5
6
7,8
2.
Potassium bromate
(>99.5%) was used as received from Fluka Chemical Co.
3.
Use of higher concentration
sulfuric acid (~2.0 M) than traditionally employed is crucial to allow complete conversion of the
2-iodobenzoic acid to
1.
2 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 to
1.
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
iodobenzoic acid and
sulfuric acid as originally described,
2 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 appears much safer
(Note 1).
8,9
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 water (~0.3 g/100 mL).
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
(Note 10) of this intermediate and/or the periodinane
2,
3
4
5
6
7 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 incomplete removal of
ethanol after the washing in an effort to avoid drying the 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.
10.
Recently, the
1H NMR of
1 in d
6 DMSO has been reported.
9 The
1H NMR spectrum of
1 prepared as described above was identical to that reported:
1H NMR (400 MHz in d
6 DMSO) δ as follows: 7.84 (t, 1 H, J = 14.8), 7.99 (t, 1 H, J = 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 calorimetry.
2,3
4
5
6
7,8
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 Company, Inc.
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.
14.
Ether was dried and deoxygenated by distillation from
sodium 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 humid environment.
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 (CH
2Cl
2) followed by analysis of the reaction mixture for
benzaldehyde by 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%.
18.
The Dess-Martin periodinane
(2) had
1H NMR (300 MHz in CDCl
3) δ as 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 (d), 8.00 (d), 7.27 (s), and 2.08 (s) (possibly the mono acetate); d
13C NMR (75 MHz in CDCl
3) δ: 20.2, 20.4, 125.9, 126.5, 131.7, 133.8, 135.8, 142.2, 166.1, 174.0, 175.7
. The checkers note that a
freshly opened bottle of
deuterochloroform
(
CDCl3
) was required to dissolve
2 and that drying of older
CDCl3
by running the solvent through
potassium carbonate (K2CO3) did not facilitate dissolution. The submitters observed the same phenomenon and believe that traces of acid in the fresh
CDCl3
may be responsible for this observation.
19.
The Dess-Martin periodinane
(2) can be stored in a
dark bottle under
argon at ~ −20°C in a freezer.
Handling and Disposal of Hazardous Chemicals
The procedures in this article are intended for use only by persons with prior training in experimental organic chemistry. All hazardous materials should be handled using the standard procedures for work with chemicals described in references such as "Prudent Practices in the Laboratory" (The National Academies Press, Washington, D.C., 2011 www.nap.edu). All chemical waste should be disposed of in accordance with local regulations. For general guidelines for the management of chemical waste, see Chapter 8 of Prudent Practices.
These procedures must be conducted at one's own risk. Organic Syntheses, Inc., its Editors, and its Board of Directors do not warrant or guarantee the safety of individuals using these procedures and hereby disclaim any liability for any injuries or damages claimed to have resulted from or related in any way to the procedures herein.
3. Discussion
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 and secondary alcohols to carbonyl compounds.
2,10 The present procedure is a variation of the Martin procedure and is based heavily upon it.
2 Modified preparations have been reported by Ireland and Schreiber.
11
12 The reported explosiveness of samples of impure
2
3
4
5
6
7 has prompted a more thorough examination of the properties of
2.
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 of
1 or the monoacetate derivatives of
1 and
2 as judged by
1H 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 material
.
8
The Dess-Martin periodinane
(2) has found wide utility as a selective oxidant in sensitive, highly functionalized intermediates commonly encountered in the synthesis of natural products and related complex molecules.
2 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 in particular].
2
A selection of cases in which
2 has been found to be particularly efficacious is given in the Table. Additional examples are cited in references
1 and
9. 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.
Appendix
Chemical Abstracts Nomenclature (Collective Index Number);
(Registry Number)
1,1,1-Triacetoxy-1,1-dihydro-1,2-benziodoxol-3(1H)-one:
1,2-Benziodoxol-3(1H)-one,
1,1,1-tris(acetyloxy)-1,1-dihydro- (11); (87413-09-0)
1-Hydroxy-1,2-benziodoxol-3(1H)-one 1-oxide:
1,2-Benziodoxol-3(1H)-one,
1-hydroxy-, 1-oxide (10); (61717-82-6)
Potassium bromate:
Bromic acid, potassium salt (8,9); (7758-01-2)
2-Iodobenzoic acid:
Benzoic acid, o-iodo- (8);
Benzoic acid, 2-iodo- (9); (88-67-5)
Bromine (8,9); (7726-95-6)
Glacial acetic acid:
Acetic acid (8,9); (64-19-7)
Acetic anhydride (8);
Acetic acid anhydride (9); (108-24-7)
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