Cornforth reagent
Encyclopedia
The Cornforth reagent or pyridinium dichromate (PDC) is a pyridinium
salt of dichromate with the chemical formula
[C5H5NH]2[Cr2O7]. This compound is named after the Australian-British chemist Sir John Warcup Cornforth
(b. 1917) who introduced it in 1962. The Cornforth reagent is a strong oxidizing agent which can convert primary
and secondary alcohol
s to aldehyde
s and ketone
s respectively. In its chemical structure and functions it is closely related to other compounds made from hexavalent chromium
oxide, such as pyridinium chlorochromate
and Collins reagent
. Because of their toxicity, these reagents are rarely used nowadays.
to pyridine
. The reaction may cause explosion, which is avoided by thoroughly dissolving the trioxide in water and cooling the solution by ice. The product is filtered, washed with acetone and dried, yielding an orange powder. The powder is stable in air, not particularly hygroscopic and has an almost neutral pH
that facilitates its handling; it is only slightly acidic owing to the presence of pyridinium cations. The Cornforth reagent is readily soluble in water, dimethylformamide
and dimethyl sulfoxide
(DMSO). It is poorly soluble in acetone
and chlorinated organic solvents, such as dichloromethane
, and forms suspensions
.
s to ketone
s, both as a solution or suspension. This application was first mentioned in 1969, but fully developed only in 1979 by Corey and Schmidt. They mentioned that reaction of saturated primary alcohols with PDC, using dimethylformamide as solvent, results in oxidation to carboxylic acid
s rather than aldehyde
s. However, no oxidation to carboxylic acids occurs on allylic and benzylic primary alcohols.
The oxidation is usually carried out at ambient conditions, in nearly neutral pH
conditions, in dimethylformamide or dichloromethane or their mixture. The choice of solvent or their ratio affects the reaction rate; in particular, higher content of dimethylformamide results in stronger oxidation. The slow oxidation rate for some alcohols can be accelerated by the addition of molecular sieve
s, organic acids or acetic anhydride
or of their combinations. The acceleration by molecular sieves works best when their pore diameter is about 0.3 nm, and it is apparently unrelated to their water absorption capability. Among organic acids, acetic acid
, pyridinium trifluoroacetate
or pyridinium tosyl
ate can be added, the first one being most efficient and easiest to remove. The achieved acceleration is remarkable, but the reaction inevitably turns from neutral (pH) to acidic. Comparable acceleration is achieved with acetic anhydride, which is used in sugar and nucleoside
chemistry. Reaction acceleration depends not only on the additives but also on their form, so all reagents are preferred dry and freshly prepared, and PDC and molecular sieves should be finely ground. The disadvantange of the accelerators is that they may simultaneously promote several oxidation routes thereby reducing the selectivity of the reaction.
In its chemical structure and functions, the Cornforth reagent is closely related to other pyridinium salts of hexavalent chromium oxide, such as pyridinium chlorochromate
[PyH][CrO3Cl] and to pyridine complexes such as the Collins reagent
, CrO3·2Py in dichloromethane and the Sarret reagent
, CrO3·2Py in pyridine.
varies between 0.01 and 0.1 mg·m–3 in air depending on the country. As a strong oxidant, pyridinium dichromate promotes fires, releasing carbon monoxide
, carbon dioxide
and toxic metal smoke. The fire can be extinguished by water or CO2.
Pyridinium
Pyridinium refers to the cationic form of pyridine. This can either be due to protonation of the ring nitrogen or because of addition of a substituent to the ring nitrogen, typically via alkylation. The lone pair of electrons on the nitrogen atom of pyridine is not delocalized, and thus pyridine...
salt of dichromate with the chemical formula
Chemical formula
A chemical formula or molecular formula is a way of expressing information about the atoms that constitute a particular chemical compound....
[C5H5NH]2[Cr2O7]. This compound is named after the Australian-British chemist Sir John Warcup Cornforth
John Cornforth
Sir John Warcup 'Kappa' Cornforth, AC, CBE, FRS , is an Australian scientist who won the Nobel Prize in Chemistry in 1975 for his work on the stereochemistry of enzyme-catalyzed reactions....
(b. 1917) who introduced it in 1962. The Cornforth reagent is a strong oxidizing agent which can convert primary
Primary alcohol
A primary alcohol is an alcohol which has the hydroxyl radical connected to a primary carbon. It can also be defined as a molecule containing a “–CH2OH” group.Examples include ethanol and butanol....
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 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 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 respectively. In its chemical structure and functions it is closely related to other compounds made from hexavalent chromium
Hexavalent chromium
Hexavalent chromium refers to chemical compounds that contain the element chromium in the +6 oxidation state. Virtually all chromium ore is processed via hexavalent chromium, specifically the salt sodium dichromate. Approximately of hexavalent chromium were produced in 1985...
oxide, such as pyridinium chlorochromate
Pyridinium chlorochromate
Pyridinium 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...
and Collins reagent
Collins reagent
Collins reagent is the complex of chromium oxide with pyridine in dichloromethane. It is used to selectively oxidize primary alcohols to the aldehyde, and will tolerate many other functional groups within the molecule....
. Because of their toxicity, these reagents are rarely used nowadays.
Synthesis and properties
The Cornforth reagent is prepared by slow addition of a concentrated aqueous solution of chromium trioxideChromium trioxide
Chromium trioxide is the inorganic compound with the formula CrO3. It is the acidic anhydride of chromic acid, and is sometimes marketed under the same name.This compound is a dark-red/orange brown solid, which dissolves in water concomitant with hydrolysis...
to pyridine
Pyridine
Pyridine is a basic heterocyclic organic compound with the chemical formula C5H5N. It is structurally related to benzene, with one C-H group replaced by a nitrogen atom...
. The reaction may cause explosion, which is avoided by thoroughly dissolving the trioxide in water and cooling the solution by ice. The product is filtered, washed with acetone and dried, yielding an orange powder. The powder is stable in air, not particularly hygroscopic and has an almost neutral pH
PH
In chemistry, pH is a measure of the acidity or basicity of an aqueous solution. Pure water is said to be neutral, with a pH close to 7.0 at . Solutions with a pH less than 7 are said to be acidic and solutions with a pH greater than 7 are basic or alkaline...
that facilitates its handling; it is only slightly acidic owing to the presence of pyridinium cations. The Cornforth reagent is readily soluble in water, dimethylformamide
Dimethylformamide
Dimethylformamide is an organic compound with the formula 2NCH. Commonly abbreviated as DMF , this colourless liquid is miscible with water and the majority of organic liquids. DMF is a common solvent for chemical reactions...
and dimethyl sulfoxide
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...
(DMSO). It is poorly soluble in acetone
Acetone
Acetone is the organic compound with the formula 2CO, a colorless, mobile, flammable liquid, the simplest example of the ketones.Acetone is miscible with water and serves as an important solvent in its own right, typically as the solvent of choice for cleaning purposes in the laboratory...
and chlorinated organic solvents, such as dichloromethane
Dichloromethane
Dichloromethane is an organic compound with the formula CH2Cl2. This colorless, volatile liquid with a moderately sweet aroma is widely used as a solvent. Although it is not miscible with water, it is miscible with many organic solvents...
, and forms suspensions
Suspension (chemistry)
In chemistry, a suspension is a heterogeneous fluid containing solid particles that are sufficiently large for sedimentation. Usually they must be larger than 1 micrometer. The internal phase is dispersed throughout the external phase through mechanical agitation, with the use of certain...
.
Applications
The Cornforth reagent is a strong oxidizing agent which can convert primary and secondary 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 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, both as a solution or suspension. This application was first mentioned in 1969, but fully developed only in 1979 by Corey and Schmidt. They mentioned that reaction of saturated primary alcohols with PDC, using dimethylformamide as solvent, results in oxidation to carboxylic acid
Carboxylic acid
Carboxylic acids are organic acids characterized by the presence of at least one carboxyl group. The general formula of a carboxylic acid is R-COOH, where R is some monovalent functional group...
s rather than 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. However, no oxidation to carboxylic acids occurs on allylic and benzylic primary alcohols.
The oxidation is usually carried out at ambient conditions, in nearly neutral pH
PH
In chemistry, pH is a measure of the acidity or basicity of an aqueous solution. Pure water is said to be neutral, with a pH close to 7.0 at . Solutions with a pH less than 7 are said to be acidic and solutions with a pH greater than 7 are basic or alkaline...
conditions, in dimethylformamide or dichloromethane or their mixture. The choice of solvent or their ratio affects the reaction rate; in particular, higher content of dimethylformamide results in stronger oxidation. The slow oxidation rate for some alcohols can be accelerated by the addition of molecular sieve
Molecular sieve
A molecular sieve is a material containing tiny pores of a precise and uniform size that is used as an adsorbent for gases and liquids.Molecules small enough to pass through the pores are adsorbed while larger molecules are not. It is different from a common filter in that it operates on a...
s, organic acids or 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...
or of their combinations. The acceleration by molecular sieves works best when their pore diameter is about 0.3 nm, and it is apparently unrelated to their water absorption capability. Among organic acids, 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...
, pyridinium trifluoroacetate
Trifluoroacetic acid
Trifluoroacetic acid is the simplest stable perfluorinated carboxylic acid chemical compound, with the formula CF3CO2H. It is a strong carboxylic acid due to the influence of the electronegative trifluoromethyl group. TFA is almost 100,000-fold more acidic than acetic acid...
or pyridinium tosyl
Tosyl
A tosyl group is CH3C6H4SO2. This group is usually derived from the compound 4-toluenesulfonyl chloride, CH3C6H4SO2Cl, which forms esters and amides of toluenesulfonic or tosylic acid...
ate can be added, the first one being most efficient and easiest to remove. The achieved acceleration is remarkable, but the reaction inevitably turns from neutral (pH) to acidic. Comparable acceleration is achieved with acetic anhydride, which is used in sugar and nucleoside
Nucleoside
Nucleosides are glycosylamines consisting of a nucleobase bound to a ribose or deoxyribose sugar via a beta-glycosidic linkage...
chemistry. Reaction acceleration depends not only on the additives but also on their form, so all reagents are preferred dry and freshly prepared, and PDC and molecular sieves should be finely ground. The disadvantange of the accelerators is that they may simultaneously promote several oxidation routes thereby reducing the selectivity of the reaction.
In its chemical structure and functions, the Cornforth reagent is closely related to other pyridinium salts of hexavalent chromium oxide, such as pyridinium chlorochromate
Pyridinium chlorochromate
Pyridinium 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...
[PyH][CrO3Cl] and to pyridine complexes such as the Collins reagent
Collins reagent
Collins reagent is the complex of chromium oxide with pyridine in dichloromethane. It is used to selectively oxidize primary alcohols to the aldehyde, and will tolerate many other functional groups within the molecule....
, CrO3·2Py in dichloromethane and the Sarret reagent
Sarett oxidation
The Sarett oxidation is the oxidation of an alcohol to a ketone or an aldehyde using chromium trioxide and pyridine. Primary alcohols will only be oxidised to the aldehyde and not on to carboxylic acids....
, CrO3·2Py in pyridine.
Safety issues
The Cornforth reagent is very toxic to aquatic life and may cause long-term damage to the environment if released in large amounts. It irritates skin and mucous membranes and may induce allergic reactions; it is carcinogenic. The maximum allowable concentrationThreshold Limit Value
The threshold limit value of a chemical substance is a level to which it is believed a worker can be exposed day after day for a working lifetime without adverse health effects. Strictly speaking, TLV is a reserved term of the American Conference of Governmental Industrial Hygienists...
varies between 0.01 and 0.1 mg·m–3 in air depending on the country. As a strong oxidant, pyridinium dichromate promotes fires, releasing carbon monoxide
Carbon monoxide
Carbon monoxide , also called carbonous oxide, is a colorless, odorless, and tasteless gas that is slightly lighter than air. It is highly toxic to humans and animals in higher quantities, although it is also produced in normal animal metabolism in low quantities, and is thought to have some normal...
, carbon dioxide
Carbon dioxide
Carbon dioxide is a naturally occurring chemical compound composed of two oxygen atoms covalently bonded to a single carbon atom...
and toxic metal smoke. The fire can be extinguished by water or CO2.