Hydrazone iodination
Encyclopedia
Hydrazone iodination is an organic reaction
in which a hydrazone
is converted into a vinyl iodide
by reaction of iodine
and a non-nucleophilic base such as DBU
. First published by D. H. R. Barton
in 1962 the reaction is sometimes referred to as the Barton reaction (although there are many different Barton reactions) or, more descriptively, as the Barton vinyl iodine procedure.
The reaction has earlier roots with the 1911 discovery by Wieland and Roseeu that the reaction of hydrazones with iodine alone (without base) results in the azine dimer (structure 2 in scheme 1).
In the original Barton publication the reaction was optimized by using a strong guanidine
base, the inverse addition of the hydrazone to an iodine solution, and by exclusion of water.
When iodine as an electrophile
is replaced by aromatic selenyl bromides, the corresponding vinyl selenides are obtained:
proposed in the original Barton publication is outlines as follows:
The hydrazone is oxidized by iodine into a diazo
intermediate. In the next step, iodine reacts as a nucleophile
; displacement of nitrogen then generates an iodocarbonium ion
. When the reaction site is not sterically hindered, a second iodide can recombine to form the geminal
di-iodide; otherwise an elimination reaction
leads to the vinyliodide. When water is present, the reaction product can revert to the ketone
.
This reaction is related to the Shapiro reaction
.
to the hydrazone by reaction with hydrazine
and triethylamine
in ethanol
at reflux
followed by reaction of the hydrazone with iodine
in the presence of 2-tert-butyl-1,1,3,3-tetramethylguanidine
(cheaper than DBU) in diethyl ether
at room temperature
. Another example can be found in the Danishefsky Taxol total synthesis
.
In one study it is attempted to trap any reactive intermediate
of this reaction with an internal alkene
. When the hydrazone 1 in scheme 5 is reacted with iodine and triethylamine
in toluene
, the expected reaction product is not the di-iodide 10 through path B in a free radical mechanism. The actual process taking place is path A with elimination
of HI to the diazo
compound 4 followed by a diazoalkane 1,3-dipolar cycloaddition
to the pyrazoline 5 in 85% yield.
Organic reaction
Organic reactions are chemical reactions involving organic compounds. The basic organic chemistry reaction types are addition reactions, elimination reactions, substitution reactions, pericyclic reactions, rearrangement reactions, photochemical reactions and redox reactions. In organic synthesis,...
in which a hydrazone
Hydrazone
Hydrazones are a class of organic compounds with the structure R1R2C=NNH2. They are related to ketones and aldehydes by the replacement of the oxygen with the NNH2 functional group...
is converted into a vinyl iodide
Vinyl halide
In organic chemistry, a vinyl halide is any alkene with at least one halide substituent bonded directly on one of the unsaturated carbons. Vinyl chloride is one such substance....
by reaction of iodine
Iodine
Iodine is a chemical element with the symbol I and atomic number 53. The name is pronounced , , or . The name is from the , meaning violet or purple, due to the color of elemental iodine vapor....
and a non-nucleophilic base such as DBU
DBU (chemistry)
1,8-Diazabicyclo[5.4.0]undec-7-ene, or more commonly DBU, is a chemical compound and belongs to the class of amidine compounds. It is used in organic synthesis as a catalyst and complexing ligand and a strong non-nucleophilic base.It is used as a curing agent for epoxy; it is used as a protecting...
. First published by D. H. R. Barton
Derek Harold Richard Barton
Sir Derek Harold Richard Barton FRS was a British organic chemist and Nobel Prize laureate.-Biography:Barton was born to William Thomas and Maude Henrietta Barton. He attended Tonbridge School and in 1938 he entered Imperial College London, where he graduated in 1940 and obtained his Ph.D. degree...
in 1962 the reaction is sometimes referred to as the Barton reaction (although there are many different Barton reactions) or, more descriptively, as the Barton vinyl iodine procedure.
The reaction has earlier roots with the 1911 discovery by Wieland and Roseeu that the reaction of hydrazones with iodine alone (without base) results in the azine dimer (structure 2 in scheme 1).
In the original Barton publication the reaction was optimized by using a strong guanidine
Guanidine
Guanidine is a crystalline compound of strong alkalinity formed by the oxidation of guanine. It is used in the manufacture of plastics and explosives. It is found in urine as a normal product of protein metabolism. The molecule was first synthesized in 1861 by the oxidative degradation of an...
base, the inverse addition of the hydrazone to an iodine solution, and by exclusion of water.
When iodine as an electrophile
Electrophile
In general electrophiles are positively charged species that are attracted to an electron rich centre. In chemistry, an electrophile is a reagent attracted to electrons that participates in a chemical reaction by accepting an electron pair in order to bond to a nucleophile...
is replaced by aromatic selenyl bromides, the corresponding vinyl selenides are obtained:
Reaction mechanism
The reaction mechanismReaction mechanism
In chemistry, a reaction mechanism is the step by step sequence of elementary reactions by which overall chemical change occurs.Although only the net chemical change is directly observable for most chemical reactions, experiments can often be designed that suggest the possible sequence of steps in...
proposed in the original Barton publication is outlines as follows:
The hydrazone is oxidized by iodine into a diazo
Diazo
Diazo refers to a type of organic compound called diazo compound that has two linked nitrogen atoms as a terminal functional group. The general formula is R2C=N2. The simplest example of a diazo compound is diazomethane...
intermediate. In the next step, iodine reacts as a nucleophile
Nucleophile
A nucleophile is a species that donates an electron-pair to an electrophile to form a chemical bond in a reaction. All molecules or ions with a free pair of electrons can act as nucleophiles. Because nucleophiles donate electrons, they are by definition Lewis bases.Nucleophilic describes the...
; displacement of nitrogen then generates an iodocarbonium ion
Carbocation
A carbocation is an ion with a positively-charged carbon atom. The charged carbon atom in a carbocation is a "sextet", i.e. it has only six electrons in its outer valence shell instead of the eight valence electrons that ensures maximum stability . Therefore carbocations are often reactive,...
. When the reaction site is not sterically hindered, a second iodide can recombine to form the geminal
Geminal
In chemistry, the term geminal refers to the relationship between two functional groups that are attached to the same atom...
di-iodide; otherwise an elimination reaction
Elimination reaction
An elimination reaction is a type of organic reaction in which two substituents are removed from a molecule in either a one or two-step mechanism...
leads to the vinyliodide. When water is present, the reaction product can revert to the 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...
.
This reaction is related to the Shapiro reaction
Shapiro reaction
The Shapiro reaction or tosylhydrazone decomposition is an organic reaction in which a ketone or aldehyde is converted to an alkene through an intermediate hydrazone in the presence of 2 equivalents of strong base. The reaction was discovered by Robert H. Shapiro in 1975...
.
Scope
An example of this procedure is the reaction of 2,2,6-trimethylcyclohexanoneCyclohexanone
Cyclohexanone is the organic compound with the formula 5CO. The molecule consists of six-carbon cyclic molecule with a ketone functional group. This colorless oil has an odor reminiscent of peardrop sweets as well as acetone. Over time, samples assume a yellow color due to oxidation...
to the hydrazone by reaction with hydrazine
Hydrazine
Hydrazine is an inorganic compound with the formula N2H4. It is a colourless flammable liquid with an ammonia-like odor. Hydrazine is highly toxic and dangerously unstable unless handled in solution. Approximately 260,000 tons are manufactured annually...
and triethylamine
Triethylamine
Triethylamine is the chemical compound with the formula N3, commonly abbreviated Et3N. It is also abbreviated TEA, yet this abbreviation must be used carefully to avoid confusion with triethanolamine, for which TEA is also a common abbreviation....
in ethanol
Ethanol
Ethanol, also called ethyl alcohol, pure alcohol, grain alcohol, or drinking alcohol, is a volatile, flammable, colorless liquid. It is a psychoactive drug and one of the oldest recreational drugs. Best known as the type of alcohol found in alcoholic beverages, it is also used in thermometers, as a...
at reflux
Reflux
Reflux is a technique involving the condensation of vapors and the return of this condensate to the system from which it originated. It is used in industrial and laboratory distillations...
followed by reaction of the hydrazone with iodine
Iodine
Iodine is a chemical element with the symbol I and atomic number 53. The name is pronounced , , or . The name is from the , meaning violet or purple, due to the color of elemental iodine vapor....
in the presence of 2-tert-butyl-1,1,3,3-tetramethylguanidine
Guanidine
Guanidine is a crystalline compound of strong alkalinity formed by the oxidation of guanine. It is used in the manufacture of plastics and explosives. It is found in urine as a normal product of protein metabolism. The molecule was first synthesized in 1861 by the oxidative degradation of an...
(cheaper than DBU) in diethyl ether
Diethyl ether
Diethyl ether, also known as ethyl ether, simply ether, or ethoxyethane, is an organic compound in the ether class with the formula . It is a colorless, highly volatile flammable liquid with a characteristic odor...
at room temperature
Room temperature
-Comfort levels:The American Society of Heating, Refrigerating and Air-Conditioning Engineers has listings for suggested temperatures and air flow rates in different types of buildings and different environmental circumstances. For example, a single office in a building has an occupancy ratio per...
. Another example can be found in the Danishefsky Taxol total synthesis
Danishefsky Taxol total synthesis
The Danishefsky Taxol total synthesis in organic chemistry is an important third Taxol synthesis published by the group of Samuel Danishefsky in 1996...
.
In one study it is attempted to trap any reactive intermediate
Reactive intermediate
In chemistry a reactive intermediate is a short-lived, high energy, highly reactive molecule. When generated in a chemical reaction it will quickly convert into a more stable molecule. Only in exceptional cases can these compounds be isolated and stored, e.g. low temperatures, matrix isolation...
of this reaction with an internal alkene
Alkene
In organic chemistry, an alkene, olefin, or olefine is an unsaturated chemical compound containing at least one carbon-to-carbon double bond...
. When the hydrazone 1 in scheme 5 is reacted with iodine and triethylamine
Triethylamine
Triethylamine is the chemical compound with the formula N3, commonly abbreviated Et3N. It is also abbreviated TEA, yet this abbreviation must be used carefully to avoid confusion with triethanolamine, for which TEA is also a common abbreviation....
in toluene
Toluene
Toluene, formerly known as toluol, is a clear, water-insoluble liquid with the typical smell of paint thinners. It is a mono-substituted benzene derivative, i.e., one in which a single hydrogen atom from the benzene molecule has been replaced by a univalent group, in this case CH3.It is an aromatic...
, the expected reaction product is not the di-iodide 10 through path B in a free radical mechanism. The actual process taking place is path A with elimination
Elimination reaction
An elimination reaction is a type of organic reaction in which two substituents are removed from a molecule in either a one or two-step mechanism...
of HI to the diazo
Diazo
Diazo refers to a type of organic compound called diazo compound that has two linked nitrogen atoms as a terminal functional group. The general formula is R2C=N2. The simplest example of a diazo compound is diazomethane...
compound 4 followed by a diazoalkane 1,3-dipolar cycloaddition
Diazoalkane 1,3-dipolar cycloaddition
The Diazoalkane 1,3-dipolar cycloaddition is a 1,3-dipolar cycloaddition between a 1,3-dipole diazo compound and a dipolarophile. When the dipolarphile is an alkene, the reaction product is a pyrazoline....
to the pyrazoline 5 in 85% yield.