Dess Martin Synthesis Essay

Names
IUPAC name

1,1,1-Triacetoxy-1,1-dihydro-1,2-benziodoxol-3(1H)-one

Other names

Dess–Martin periodinane

Identifiers

CAS Number

3D model (JSmol)

ChemSpider
ECHA InfoCard100.197.885

PubChemCID

InChI

  • InChI=1S/C13H13IO8/c1-8(15)19-14(20-9(2)16,21-10(3)17)12-7-5-4-6-11(12)13(18)22-14/h4-7H,1-3H3

    Key: NKLCNNUWBJBICK-UHFFFAOYSA-N

  • InChI=1S/C13H13IO8/c1-8(15)19-14(20-9(2)16,21-10(3)17)12-7-5-4-6-11(12)13(18)22-14/h4-7H,1-3H3

    Key: NKLCNNUWBJBICK-UHFFFAOYAQ

SMILES

  • CC(=O)OI1(c2ccccc2C(=O)O1)(OC(=O)C)OC(=O)C

Properties

Chemical formula

C13H13IO8
Molar mass424.14 g/mol
Appearancewhite powder, chips,
crystals or crystalline
powder and/or chunks
Density1.362 g/cm3 solid
Melting point103 to 133 °C (217 to 271 °F; 376 to 406 K)
Related compounds

Related compounds

2-Iodoxybenzoic acid

Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).

Infobox references

Dess–Martin periodinane (DMP) is a chemical reagent used to oxidize primary alcohols to aldehydes and secondary alcohols to ketones.[1][2] This periodinane has several advantages over chromium- and DMSO-based oxidants that include milder conditions (room temperature, neutral pH), shorter reaction times, higher yields, simplified workups, high chemoselectivity, tolerance of sensitive functional groups, and a long shelf life. It is named after the American chemists Daniel Benjamin Dess and James Cullen Martin who developed the reagent in 1983. It is based on IBX, but due to the acetate groups attached to the central iodine atom, DMP is much more reactive than IBX and is much more soluble in organic solvents.[3]

Preparation[edit]

The most friendly synthesis of IBX has been determined to be treating 2-iodobenzoic acid with oxone in water, at elevated temperatures for 3 hours.[4] IBX is then acylated using Ireland and Liu’s [5] modifications from the original procedure. These modifications allowed for higher yields and a simplified work up procedure. The resulted solids can be obtained via filtration and washing with ether. Ireland and Liu used a catalytic amount of tosylic acid, which allowed the reaction to complete in less than 2 hours (compared to the classic synthesis, utilizing 24 hours) and in yields exceeding 90%.

The classic method presented by Boeckman and Mullins[6] involved heating a solution of potassium bromate, sulfuric acid, 2-iodobenzoic acid to afford IBX (1-hydroxy-1,2-benziodoxol-3(1H)-one 1-oxide, 2-iodoxybenzoic acid). IBX was then acylated using acetic acid and acetic anhydride.

Plumb and Harper[7] reported that both 2-iodoxybenzoic acid and DMP were tested to determine their ability to explode, and both samples reacted violently.

Oxidation mechanism[edit]

Dess–Martin periodinane is mainly used as an oxidant for complex, sensitive and multifunctional alcohols. One of the reasons for its effectiveness is its high selectivity towards complexation of the hydroxyl group, which allows alcohols to rapidly perform ligand exchange; the first step in the oxidation reaction.

Proton NMR has indicated that using one equivalent of alcohol forms the intermediate diacetoxyalkoxyperiodinane. The acetate then acts as a base to deprotonate the α-H from the alcohol to afford the carbonyl compound, iodinane, and acetic acid.

When a diol or more than one equivalent of alcohol is used, acetoxydialkoxyperiodinane is formed instead. Due to the labile nature of this particular periodinane, oxidation occurs much faster.[3]

Schreiber and coworkers have shown that water increases the rate of the oxidation reaction.[8] Dess and Martin had originally observed that the oxidation of ethanol was increased when there was an extra equivalent of ethanol. It is believed that the rate of dissociation of the final acetate ligand from the iodine is increased, because of the electron-donating ability of the hydroxyl group (thus weakening the I-OAc bond).[3]

Chemoselectivity[edit]

Using the standard Dess–Martin periodinane conditions, alcohols can be oxidized to aldehydes/ketones without affecting furan rings, sulfides, vinyl ethers, and secondary amides.[3] Allylic alcohols are easily oxidized using DMP, which are typically difficult to convert to their respective carbonyls using the typical oxidants.[9]

Myers and coworkers determined that DMP could oxidize N-protected-amino alcohols, without epimerization (unlike most other oxidants, including Swern oxidation). These protected amino alcohols can be very important in the pharmaceutical industry.[10]

Benzylic and allylic alcohols react faster than saturated alcohols,[3] while DMP oxidizes aldoximes and ketoximes to their respective aldehydes and ketones, faster than a primary, secondary or benzylic alcohol to its respective carbonyl.[11]

In one example of the Dess–Martin oxidation, involves transforming a sensitive α-β-unsaturated alcohol to its corresponding aldehyde. This moiety has been found in several natural products and due to its high functionality, it could be a valuable synthetic building block in organic synthesis. Thongsornkleeb and Danheiser oxidized this sensitive alcohol by employing the Dess Martin Oxidation and altering the work up procedure (diluting with pentanes, washing with poly(4-vinylpyridine) to remove the acetic acid generated during the reaction, filtering and concentrating via distillation.[12]

t-Butyl DMP[edit]

Difluoro and monofluoro alcohols are more difficult to oxidize. Swern oxidation has been used, but a large excess of the oxidant had to be employed, and in some cases did not give reproducible results. Linderman and Graves[13] found DMP was partially successful, but side reactions occurred. Using the compound shown below, produced the wanted carbonyl in high yields. The reason Linderman and Graves chose tert-butyl alcohol as a functionality instead of acetate was due to its steric bulk, thus minimizing the formation of unwanted acetic acid.

See also[edit]

References[edit]

External links[edit]

  1. ^Dess, D. B.; Martin, J. C. (1983). "Readily accessible 12-I-5 oxidant for the conversion of primary and secondary alcohols to aldehydes and ketones". J. Org. Chem.48: 4155. doi:10.1021/jo00170a070. 
  2. ^Boeckman, R. J. In "Encyclopedia of Reagents for Organic Synthesis"; Paquette, L. A., Ed.; Wiley: Chichester, UK, 1995, Vol. 7, pp. 4982–4987. (Review)
  3. ^ abcdeDess, D. B.; Martin, J. C. (1991). "A useful 12-I-5 triacetoxyperiodinane (the Dess-Martin periodinane) for the selective oxidation of primary or secondary alcohols and a variety of related 12-I-5 species". J. Am. Chem. Soc.113: 7277. doi:10.1021/ja00019a027. 
  4. ^Frigerio, M.; Santagostino, M.; Sputore, S. (1999). "A User-Friendly Entry to 2-Iodoxybenzoic Acid (IBX)". J. Org. Chem.64: 4537. doi:10.1021/jo9824596. 
  5. ^Ireland, R. E.; Liu, L. (1993). "An improved procedure for the preparation of the Dess-Martin periodinane". J. Org. Chem.58: 2899. doi:10.1021/jo00062a040. 
  6. ^Boeckman Jr., R. K.; Shao, P.; Mullins, J. J. (2004). "The Dess-Martin Periodinane". Organic Syntheses.  ; Collective Volume, 10, p. 696 
  7. ^Plumb, J.B.; Harper, D.J. (1990). "Chemical Safety: 2-Iodoxybenzoic acid". Chem. Eng. News. 68: 3. doi:10.1021/cen-v068n029.p002. 
  8. ^Meyer, S. D.; Schreiber, S. L. (1994). "Acceleration of the Dess-Martin Oxidation by Water". J. Org. Chem.59: 7549. doi:10.1021/jo00103a067. 
  9. ^Lawrence, N.J.; Crump, J.P.; McGown, A.T.; Hadfield, J.A. (2001). "Reaction of Baylis-Hillman products with Swern and Dess-Martin oxidants". Tetrahedron Lett.42: 3939. doi:10.1016/S0040-4039(01)00587-1. 
  10. ^Myers, A.G.; et al. (2000). "Synthesis of highly epimerizable N-protected _-amino aldehydes of high enantiomeric excess". Tetrahedron Lett.41: 1359. doi:10.1016/S0040-4039(99)02293-5. 
  11. ^Chaudhari, S.S.; Akamanchi, K.G. (1999). "A mild, chemoselective, oxidative method for deoximation using Dess-Martin periodinane". Synthesis. 1999: 760. doi:10.1055/s-1999-3476. 
  12. ^Thongsornkleeb, C.; Danheiser, R.L. (2005). "A Practical Method for the Synthesis of 2-Alkynylpropenals". J. Org. Chem.70: 2364. doi:10.1021/jo047869a. 
  13. ^Linderman, R.J.; Graves, D.M. (1989). "Oxidation of Fluoroalkyl-Substituted Carbinols by the Dess-Martin reagent". J. Org. Chem.54: 661. doi:10.1021/jo00264a029. 

-The oxidation of alcohols by Dess-Martin periodinane (DMP).

-The reaction proceeds at room temperature, converting alcohols into aldehydes.

-Reactive and mild enough to be used for sterically hindered alcohols and α-substituted carbonyl compounds prone to racemization.

-Used frequently in the synthesis of complex molecules.

-Can be used for many acid- and base-sensitive compounds. For compounds that are sensitive to the slight acidity of the two equivalents of acetic acid produced by the reaction, DMP can be used with the addition of a buffer such as pyridine.

・Dess, D. B.; Martin, J. C. J. Org. Chem.1983, 48, 4155. DOI:10.1021/jo00170a070
・Dess, D. B.; Matrin, J. C. J. Am. Chem. Soc.1991, 113, 7277. doi:10.1021/ja00019a027
・Stevenson, P. J.; Treacy, A. B. J. C. S. Perkin Trans. 2 1997, 589. DOI: 10.1039/a605253c

DMP is a highly functional group tolerant reagent as shown in the example below. It is used regularly in natural product synthesis. The addition of water occasionally shows beneficial effects.

Example 1.[1]

Example 2.[2]

The synthesis of spongistatin 2.[3]

The DMP reagent is readily prepared from 2-iodobenzoic acid. The preparation method reported in the original paper was somewhat irreproducible, but the modified method that uses catalytic TsOH solved the problem. The oxidation to IBX can be done reasonably safely and easily using Oxone.

The reaction workup is very simple: The mixture can either be diluted with ether and washed with aqueous NaOH or NaHCO3/Na2SO3, or directly subjected to column purification.

DMP used to be unavailable commercially because of its explosive potential, but it is available today with the establishment of improved preparation procedures. Since it is a relatively expensive reagent, one needs to prepare it him/herself for a large scale experiment. In that case, note that the activity of the reagent tends to vary depending on the amount of residual water from the workup. DMP and its synthetic precursor (IBX) are hypervalent iodine compounds whose risks as explosives are well known, thus one must plan experimental scale carefully and handle the reagent with necessary caution.

[1] 大学院講義有機化学(Japanese book) II p.174
[2] ファルマシア (Japanese magazine) 1996, 32(9)
[3] Smith, A. B., III et al. Angew. Chem. Int. Ed.2001, 40, 196. [abstract]
[4] (a) Dess, D.B.; Martin, J. C. J. Org. Chem.1983, 48, 4155. (b) idem.J. Am. Chem. Soc.1991, 113, 7277. doi:10.1021/ja00019a027 (c) Stevenson, P. J.; Treacy, A. B. J. C. S. Perkin Trans. 2 1997, 589.
[5] Irekand, R.E.; Liu, L. J. Org . Chem.1993, 58, 2899. DOI: 10.1021/jo00062a040
[6] Frigerio, M.; Sntagostino, M.; Sputore, S. J. Org. Chem. 1999, 64, 4537. DOI: 10.1021/jo9824596

 

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oxidation of alcohols, synthesis of aldehydes and ketones
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