In organic chemistry, the diazo group is an organic moiety consisting of two linked nitrogen atoms at the terminal position. Overall charge-neutral containing the diazo group bound to a carbon atom are called diazo compounds or diazoalkanes and are described by the general structural formula . The simplest example of a diazo compound is diazomethane, . Diazo compounds () should not be confused with () or with diazonium compounds ().
Structure
The electronic structure of diazo compounds is characterized by π electron density delocalized over the α-carbon and two nitrogen atoms, along with an orthogonal π system with electron density delocalized over only the terminal nitrogen atoms. Because all
octet rule-satisfying resonance forms of diazo compounds have formal charges, they are members of a class of compounds known as 1,3-dipoles. Some of the most stable diazo compounds are α-diazo-β-diketones and α-diazo-β-diesters, in which the electron density is further delocalized into an electron-withdrawing carbonyl group. In contrast, most diazoalkanes without electron-withdrawing substituents, including diazomethane itself, are explosive. A commercially relevant diazo compound is ethyl diazoacetate (N
2CHCOOEt). A group of isomeric compounds with only few similar properties are the
, where the carbon and two nitrogens are linked as a ring.
Four resonance structures can be drawn:[F.A. Carey R.J. Sundberg Advanced Organic Chemistry, 2nd Edition]
Compounds with the diazo moiety should be distinguished from diazonium compounds, which have the same terminal azo group but bear an overall positive charge, and azo compounds in which the azo group bridges two organic substituents.
History
Diazo compounds were first produced by
Peter Griess who had discovered a versatile new chemical reaction, as detailed in his 1858 paper "Preliminary notice on the influence of nitrous acid on aminonitro- and aminodinitrophenol."
[Trevor I. Williams, 'Griess, (Johann) Peter (1829–1888)', Oxford Dictionary of National Biography, Oxford University Press, 2004][Peter Griess (1858) "Vorläufige Notiz über die Einwirkung von salpetriger Säure auf Amidinitro- und Aminitrophenylsäure," (Preliminary notice of the reaction of nitrous acid with picramic acid and aminonitrophenol), Annalen der Chemie und Pharmacie, 106 : 123-125.]
Synthesis
Several methods exist for the preparation of diazo compounds.
[ New Syntheses of Diazo Compounds Gerhard Maas Angew. Chem. Int. Ed. 2009, 48, 8186 – 8195 ]
From amines or nitrosamines
Alkyl-acyl
in base dehydrate to diazo compounds:
[Example: Organic Syntheses, Coll. Vol. 6, p.981 (1988); Vol. 57, p.95 (1977). Link]
Examples are the laboratory synthesis of diazomethane from
diazald or
MNNG.
In some cases, the nitrosamine can be produced in situ without base. Primary aliphatic R-CH2-NH2 with an α acceptor (R = COOR, CN, CHO, COR) in nitrous acid directly generate a diazo compound.
From hydrazones
are oxidized (
dehydrogenation) for example with
silver oxide or
mercury oxide for example the synthesis of from acetone hydrazone.
[Organic Syntheses, Coll. Vol. 6, p.392 (1988); Vol. 50, p.27 (1970). Link] Other oxidizing reagents are lead tetraacetate, manganese dioxide and the
Swern reagent.
RRC=N-NHTs are reacted with base for example
triethylamine in the synthesis of crotyl diazoacetate
[Organic Syntheses, Coll. Vol. 5, p.258 (1973); Vol. 49, p.22 (1969). Link] and in the synthesis of phenyldiazomethane from PhCHNHTs and
sodium methoxide.
[Organic Syntheses, Coll. Vol. 7, p.438 (1990); Vol. 64, p.207 (1986).http://www.orgsyn.org/orgsyn/prep.asp?prep=CV7P0438]
Reaction of a carbonyl group with the hydrazine 1,2-bis(tert-butyldimethylsilyl)hydrazine to form the hydrazone is followed by reaction with the iodane difluoroiodobenzene yields the diazo compound:[ Elusive Natural Product Is Synthesized Stu Borman Chemical & Engineering News October 31, 2006 Link .]
From diazomethyl compounds
An example of an electrophilic substitution using a diazomethyl compound is the Nierenstein reaction between an
acyl halide and
diazomethane.
[Example Organic Syntheses, Coll. Vol. 3, p.119 (1955); Vol. 26, p.13 (1946). Link] The same reaction is the first step in the Arndt-Eistert synthesis.
By diazo transfer
In
diazo transfer, sometimes called
Regitz diazo transfer, certain
react with
and a weak base like
triethylamine or DBU, with corresponding
sulfonamide byproduct.
[M. Regitz, Angew. Chem., 79, 786 (1967); Angew. Chem. Intern. Ed. Engl., 6, 733 (1967).] The mechanism involves
enolate attack at the terminal nitrogen, proton transfer, and sulfonamide anion expulsion.
[
]
Historically, Regitz transferred from tosyl azide, but modern transfer uses reagents that are less explosive or more easily separated from the reaction products. These include imidazole-1-sulfonyl azide, , and methanesulfonyl azide.
Simple examples synthesize tert-butyl diazoacetate,[Organic Syntheses, Coll. Vol. 5, p.179 (1973); Vol. 48, p.36 (1968). Link] diazomalonate,[Organic Syntheses, Coll. Vol. 6, p.414 (1988); Vol. 59, p.66 (1979). Link] or methyl phenyldiazoacetate (from methyl phenylacetate).
In a more complicated example, phenacyl bromide reacts with trimethylphosphite and then sodium hydride and methanesulfonyl azide to give a diazo product that converts aldehydes into alkynes. This method resembles the Ohira-Bestmann reagent but is significantly more expensive.
From azides
One method is described for the synthesis of diazo compounds from using phosphines:[ A Phosphine-Mediated Conversion of Azides into Diazo Compounds Eddie L. Myers and Ronald T. Raines Angew. Chem. Int. Ed. 2009, 48, 2359 –2363 ]
Reactions
In cycloadditions
Diazo compounds react as 1,3-dipoles in diazoalkane 1,3-dipolar cycloadditions.
As carbene precursors
Diazo compounds are used as precursors to , which are generated by thermolysis or photolysis, for example in the Wolff rearrangement. (In this regard, they resemble .) As such they are used in cyclopropanation for example in the reaction of ethyl diazoacetate with styrene.[Organic Syntheses, Coll. Vol. 6, p.913 (1988); Vol. 50, p.94 (1970). Link] Certain diazo compounds can couple to form in a formal carbene dimerization reaction.
Diazo compounds are intermediates in the Bamford–Stevens reaction of to alkenes, again with a carbene intermediate:
In the Doyle–Kirmse reaction, certain diazo compounds react with allyl sulfides to the homoallyl sulfide. Intramolecular reactions of diazocarbonyl compounds provide access to cyclopropanes. In the Buchner ring expansion, diazo compounds react with aromatic rings with ring-expansion.
As nucleophile
The Buchner-Curtius-Schlotterbeck reaction yields ketones from aldehydes and aliphatic diazo compounds:
The reaction type is nucleophilic addition.
Occurrence in nature
Several families of naturally occurring products feature the diazo group. The and lomaiviticin are DNA intercalating molecules, with the diazo functionality as their "warheads". In the presence of a reducing agent, loss of N2 occurs to generate a DNA-cleaving fluorenyl radical.
One biochemical process for diazo formation is the L-aspartate-nitro-succinate (ANS) pathway. It involves a sequence of enzyme-mediated redox reactions to generate nitrite by way of a nitrosuccinic acid intermediate. This pathway appears to be active in several different Streptomyces species, and homologous genes appear widespread in actinobacteria.
See also
Notes
