Dess-Martin periodinane
Encyclopedia
Dess–Martin periodinane (DMP) is a chemical reagent used to oxidize primary alcohols
to aldehyde
s and secondary alcohol
s to ketone
s. 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 soluble in organic solvents.
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 Lui 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 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 reported that both 2-iodoxybenzoic acid and DMP were tested to determine their ability to explode, and both samples reacted violently.
s. One of the reasons for its effectiveness is its high selectivity towards complexation of the hydroxylic
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.
Meyer and coworkers have shown that water increases the rate of the oxidation reaction. 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).
rings, sulfides, vinyl ethers
, and secondary amides. Allylic alcohols are easily oxidized using DMP, which are typically difficult to convert to their respective carbonyls using the typical oxidants.
Myers and coworkers determined that DMP could oxidize N-protected-amino alcohols, without epimerization (unlike most other oxidants, including Swern oxidation). These proctected amino alcohols can be very important in the pharmaceutical industry.
Benzylic and allylic alcohols react faster than saturated alcohols, while DMP oxidizes aldoximes and ketoximes to their respective aldehydes and ketones, faster than a primary, secondary or benzylic alcohol to its respective carbonyl.
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.
has been used, but a large excess of the oxidant had to be employed, and in some cases did not produce repeatable results. Linderman and Graves found DMP was partially successful, but side reactions occurred. Using the modified DM oxidant shown below, produced the wanted carbonyl in high yields. The reason Linderman and Graves chose tert-butyl alcohol as a ligand instead of acetate was due to its bulk and nonoxidizable characteristics. This was to minimize the unwanted byproduct acetic acid formed.
Alcohol oxidation
Alcohol oxidation is an important organic reaction. Primary alcohols can be oxidized either to aldehydes or to carboxylic acids , while the oxidation of secondary alcohols normally terminates at the ketone stage...
to aldehyde
Aldehyde
An aldehyde is an organic compound containing a formyl group. This functional group, with the structure R-CHO, consists of a carbonyl center bonded to hydrogen and an R group....
s and secondary alcohol
Alcohol
In chemistry, an alcohol is an organic compound in which the hydroxy functional group is bound to a carbon atom. In particular, this carbon center should be saturated, having single bonds to three other atoms....
s to ketone
Ketone
In organic chemistry, a ketone is an organic compound with the structure RCR', where R and R' can be a variety of atoms and groups of atoms. It features a carbonyl group bonded to two other carbon atoms. Many ketones are known and many are of great importance in industry and in biology...
s. This periodinane
Periodinane
Periodinanes are chemical compounds containing hypervalent iodine. These iodine compounds are hypervalent because the iodine atom in it contains more than the 8 electrons in the valence shell required for the octet rule...
has several advantages over chromium
Chromium
Chromium is a chemical element which has the symbol Cr and atomic number 24. It is the first element in Group 6. It is a steely-gray, lustrous, hard metal that takes a high polish and has a high melting point. It is also odorless, tasteless, and malleable...
- and DMSO
Dimethyl sulfoxide
Dimethyl sulfoxide is an organosulfur compound with the formula 2SO. This colorless liquid is an important polar aprotic solvent that dissolves both polar and nonpolar compounds and is miscible in a wide range of organic solvents as well as water...
-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
James Cullen Martin
James Cullen Martin was an American chemist. He specialized in organic chemistry and main group element chemistry with an emphasis on physical organic chemistry....
who developed the reagent in 1983. It is based on IBX
2-Iodoxybenzoic acid
IBX acid or 2-iodoxybenzoic acid is an organic compound used in organic synthesis as an oxidizing agent. This Periodinane is especially suited to oxidize alcohols to aldehydes. The IBX acid is prepared from 2-iodobenzoic acid, potassium bromate and sulfuric acid...
, but due to the acetate groups attached to the central iodine atom, DMP is much more soluble in organic solvents.
Preparation
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. IBX is then acylated using Ireland and Liu’smodifications 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 Lui used a catalytic amount of tosylic acid
P-Toluenesulfonic acid
p-Toluenesulfonic acid or tosylic acid is an organic compound with the formula CH3C6H4SO3H. It is a white solid that is soluble in water, alcohols, and other polar organic solvents. The 4-CH3C6H4SO2- group is known as the Tosyl group and is often abbreviated as Ts or Tos...
, 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 involved heating a solution of potassium bromate
Potassium bromate
Potassium bromate , is a bromate of potassium and takes the form of white crystals or powder.-Uses in baking:Potassium bromate is typically used as a flour improver , strengthening the dough and allowing higher rising. It is an oxidizing agent, and under the right conditions, will be completely...
, sulfuric acid
Sulfuric acid
Sulfuric acid is a strong mineral acid with the molecular formula . Its historical name is oil of vitriol. Pure sulfuric acid is a highly corrosive, colorless, viscous liquid. The salts of sulfuric acid are called sulfates...
, 2-iodobenzoic acid
2-Iodobenzoic acid
2-Iodobenzoic acid, or o-iodobenzoic acid, is an organic compound with the formula IC6H4COOH. The synthesis of 2-iodobenzoic acid via the diazotization of anthranilic acid is a common performed in university organic chemistry labs.- Synthesis :...
to afford IBX (1-hydroxy-1,2-benziodoxol-3(1H)-one 1-oxide, 2-iodoxybenzoic acid
2-Iodoxybenzoic acid
IBX acid or 2-iodoxybenzoic acid is an organic compound used in organic synthesis as an oxidizing agent. This Periodinane is especially suited to oxidize alcohols to aldehydes. The IBX acid is prepared from 2-iodobenzoic acid, potassium bromate and sulfuric acid...
). IBX was then acylated using acetic acid and acetic anhydride
Acetic anhydride
Acetic anhydride, or ethanoic anhydride, is the chemical compound with the formula 2O. Commonly abbreviated Ac2O, it is the simplest isolatable acid anhydride and is a widely used reagent in organic synthesis...
.
Plumb and Harper reported that both 2-iodoxybenzoic acid and DMP were tested to determine their ability to explode, and both samples reacted violently.
Oxidation mechanism
Dess–Martin periodinane is mainly used as an oxidant for complex, sensitive and multifunctional alcoholAlcohol
In chemistry, an alcohol is an organic compound in which the hydroxy functional group is bound to a carbon atom. In particular, this carbon center should be saturated, having single bonds to three other atoms....
s. One of the reasons for its effectiveness is its high selectivity towards complexation of the hydroxylic
Hydroxide
Hydroxide is a diatomic anion with chemical formula OH−. It consists of an oxygen and a hydrogen atom held together by a covalent bond, and carrying a negative electric charge. It is an important but usually minor constituent of water. It functions as a base, as a ligand, a nucleophile, and a...
group, which allows alcohols to rapidly perform ligand
Ligand
In coordination chemistry, a ligand is an ion or molecule that binds to a central metal atom to form a coordination complex. The bonding between metal and ligand generally involves formal donation of one or more of the ligand's electron pairs. The nature of metal-ligand bonding can range from...
exchange; the first step in the oxidation reaction.
Proton NMR
Proton NMR
Proton NMR is the application of nuclear magnetic resonance in NMR spectroscopy with respect to hydrogen-1 nuclei within the molecules of a substance, in order to determine the structure of its molecules. In samples where natural hydrogen is used, practically all of the hydrogen consists of the...
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
Carbonyl
In organic chemistry, a carbonyl group is a functional group composed of a carbon atom double-bonded to an oxygen atom: C=O. It is common to several classes of organic compounds, as part of many larger functional groups....
compound, iodinane, and acetic acid
Acetic acid
Acetic acid is an organic compound with the chemical formula CH3CO2H . It is a colourless liquid that when undiluted is also called glacial acetic acid. Acetic acid is the main component of vinegar , and has a distinctive sour taste and pungent smell...
.
When a diol
Diol
A diol or glycol is a chemical compound containing two hydroxyl groups A geminal diol has two hydroxyl groups bonded to the same atom...
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.
Meyer and coworkers have shown that water increases the rate of the oxidation reaction. 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
Electron donor
An electron donor is a chemical entity that donates electrons to another compound. It is a reducing agent that, by virtue of its donating electrons, is itself oxidized in the process....
ability of the hydroxyl group (thus weakening the I-OAc bond).
Chemoselectivity
Using the standard Dess–Martin periodinane conditions, alcohols can be oxidized to aldehydes/ketones without affecting furanFuran
Furan is a heterocyclic organic compound, consisting of a five-membered aromatic ring with four carbon atoms and one oxygen. The class of compounds containing such rings are also referred to as furans....
rings, sulfides, vinyl ethers
Enol ether
An enol ether is an alkene with an alkoxy substituent. The general structure is R_1R_2C=CR_3-O-R_4 with R an alkyl or an aryl group. Enol ethers and enamines are so-called activated alkenes or electron rich alkenes because the oxygen atom donates electrons to the double bond by forming a resonance...
, and secondary amides. Allylic alcohols are easily oxidized using DMP, which are typically difficult to convert to their respective carbonyls using the typical oxidants.
Myers and coworkers determined that DMP could oxidize N-protected-amino alcohols, without epimerization (unlike most other oxidants, including Swern oxidation). These proctected amino alcohols can be very important in the pharmaceutical industry.
Benzylic and allylic alcohols react faster than saturated alcohols, while DMP oxidizes aldoximes and ketoximes to their respective aldehydes and ketones, faster than a primary, secondary or benzylic alcohol to its respective carbonyl.
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.
t-Butyl DMP
Difluoro and monofluoro alcohols are more difficult to oxidize. Swern oxidationSwern oxidation
The Swern oxidation, named after Daniel Swern, is a chemical reaction whereby a primary or secondary alcohol is oxidized to an aldehyde or ketone using oxalyl chloride, dimethyl sulfoxide and an organic base, such as triethylamine...
has been used, but a large excess of the oxidant had to be employed, and in some cases did not produce repeatable results. Linderman and Graves found DMP was partially successful, but side reactions occurred. Using the modified DM oxidant shown below, produced the wanted carbonyl in high yields. The reason Linderman and Graves chose tert-butyl alcohol as a ligand instead of acetate was due to its bulk and nonoxidizable characteristics. This was to minimize the unwanted byproduct acetic acid formed.
See also
- Swern oxidationSwern oxidationThe Swern oxidation, named after Daniel Swern, is a chemical reaction whereby a primary or secondary alcohol is oxidized to an aldehyde or ketone using oxalyl chloride, dimethyl sulfoxide and an organic base, such as triethylamine...
- Parikh-Doering oxidationParikh-Doering oxidationThe Parikh-Doering oxidation is an oxidation reaction that transforms primary and secondary alcohols into aldehydes and ketones, respectively. The procedure uses DMSO as the oxidant, activated by sulfur trioxide-pyridine complex in the presence of triethylamine base:The procedure can be run at...
- Corey–Kim oxidation
- Pfitzner–Moffatt oxidation
- Pyridinium chlorochromatePyridinium chlorochromatePyridinium chlorochromate is a reddish orange solid reagent used to oxidize primary alcohols to aldehydes and secondary alcohols to ketones. Pyridinium chlorochromate, or PCC, will not fully oxidize a primary alcohol to the carboxylic acid as does the Jones reagent. A disadvantage to using PCC is...
- Jones oxidationJones oxidationThe Jones oxidation, is an organic reaction for the oxidation of primary and secondary alcohols to carboxylic acids and ketones, respectively. It is named after its discoverer, Sir Ewart Jones....
- Ley oxidation
- Oppenauer oxidationOppenauer oxidationOppenauer oxidation, named after Rupert Viktor Oppenauer, is a gentle method for selectively oxidizing secondary alcohols to ketones.The reaction is the opposite of Meerwein-Ponndorf-Verley reduction. The alcohol is oxidized with aluminium isopropoxide in excess acetone...