Jump to content

Diazo

From Wikipedia, the free encyclopedia
For a discussion of copiers using the diazo process, see whiteprint. For the software, see Diazo (software).
Diazo compounds have two main Lewis structures in resonance: R2>C−–N+≡N and R2>CH=N+=N−
Diazo compounds have two main Lewis structures in resonance: R2>C−–N+≡N and R2>CH=N+=N−

In organic chemistry, the diazo group is an organic moiety consisting of two linked nitrogen atoms at the terminal position. Overall charge-neutral organic compounds containing the diazo group bound to a carbon atom are called diazo compounds or diazoalkanes[a] and are described by the general structural formula R2C=N+=N−. The simplest example of a diazo compound is diazomethane, CH2N2. Diazo compounds (R2C=N2) should not be confused with azo compounds (R−N=N−R) or with diazonium compounds (R−N+2).

Structure

[edit]

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 (N2CHCOOEt). A group of isomeric compounds with only few similar properties are the diazirines, where the carbon and two nitrogens are linked as a ring.

Four resonance structures can be drawn:[1]

Diazo resonance structures

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

[edit]

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."[2][3]

Synthesis

[edit]

Several methods exist for the preparation of diazo compounds.[4][5]

From amines or nitrosamines

[edit]

Alkyl-acyl nitrosamines in base dehydrate to diazo compounds:[6]

Diazo synthesis from N-alkyl-N-nitroso compounds
The mechanism shown here is one possibility;[7] see diazald for an alternative.

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 amines R-CH2-NH2 with an α acceptor (R = COOR, CN, CHO, COR) in nitrous acid directly generate a diazo compound.

From hydrazones

[edit]

Hydrazones are oxidized (dehydrogenation) for example with silver oxide or mercury oxide for example the synthesis of 2-diazopropane [fr] from acetone hydrazone.[8] Other oxidizing reagents are lead tetraacetate, manganese dioxide and the Swern reagent. Tosyl hydrazones RRC=N-NHTs are reacted with base for example triethylamine in the synthesis of crotyl diazoacetate[9] and in the synthesis of phenyldiazomethane from PhCHNHTs and sodium methoxide.[10]

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:[11][12]

Kinamycin C synthesis

From diazomethyl compounds

[edit]

An example of an electrophilic substitution using a diazomethyl compound is that of a reaction between an acyl halide and diazomethane,[13] for example the first step in the Arndt-Eistert synthesis.

By diazo transfer

[edit]
Solid state structure of the diazo compound t-BuO2CC(N2)C6H4NO2. Key distances: C-N = 1.329 Å, N-N = 1.121 Å.[14]

In diazo transfer, sometimes called Regitz diazo transfer, certain carbon acids react with sulfonyl azides and a weak base like triethylamine or DBU, with corresponding sulfonamide byproduct.[15] The mechanism involves enolate attack at the terminal nitrogen, proton transfer, and sulfonamide anion expulsion.[16]

Mechanism for diazomalonate from malonic acid and tosyl azide

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, p‑acetanilide­sulfonyl azide [de], and methanesulfonyl azide.[17] β-Carbonyl aldehydes undergo a deformylative variant to give primary diazo compounds stabilized by only the ketone.[16]

Simple examples synthesize tert-butyl diazoacetate,[18] diazomalonate,[19] or methyl phenyldiazoacetate (from methyl phenylacetate).[20][21]

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.[22]

From azides

[edit]

One method is described for the synthesis of diazo compounds from azides using phosphines:[23]

Azide to diazo conversion

Reactions

[edit]

In cycloadditions

[edit]

Diazo compounds react as 1,3-dipoles in diazoalkane 1,3-dipolar cycloadditions.

As carbene precursors

[edit]

Diazo compounds are used as precursors to carbenes, which are generated by thermolysis or photolysis, for example in the Wolff rearrangement. (In this regard, they resemble diazirenes.) As such they are used in cyclopropanation for example in the reaction of ethyl diazoacetate with styrene.[24] Certain diazo compounds can couple to form alkenes in a formal carbene dimerization reaction.

Diazo compounds are intermediates in the Bamford–Stevens reaction of tosylhydrazones to alkenes, again with a carbene intermediate:

Bamford-Stevens reaction

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

[edit]

The Buchner-Curtius-Schlotterbeck reaction yields ketones from aldehydes and aliphatic diazo compounds:

Buchner-Curtius-Schlotterbeck reaction

The reaction type is nucleophilic addition.

Occurrence in nature

[edit]

Several families of naturally occurring products feature the diazo group. The kinamycins 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.[25]

See also

[edit]

Notes

[edit]
  1. ^ The term diazoalkane is used by some authors to refer to any substituted diazomethane (i.e., all diazo compounds). However, other authors use the term to refer exclusively to diazo compounds with alkyl substituents that do not contain other functional groups (which would exclude compounds like diazo(diphenyl)methane or ethyl diazoacetate).

References

[edit]
  1. ^ F.A. Carey R.J. Sundberg Advanced Organic Chemistry, 2nd Edition
  2. ^ Trevor I. Williams, 'Griess, (Johann) Peter (1829–1888)', Oxford Dictionary of National Biography, Oxford University Press, 2004
  3. ^ 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.
  4. ^ March, Jerry (1985). Advanced Organic Chemistry: Reactions, Mechanisms, and Structure (3rd ed.). New York: Wiley. ISBN 9780471854722. OCLC 642506595.
  5. ^ New Syntheses of Diazo Compounds Gerhard Maas Angew. Chem. Int. Ed. 2009, 48, 8186 – 8195 doi:10.1002/anie.200902785
  6. ^ Example: Organic Syntheses, Coll. Vol. 6, p.981 (1988); Vol. 57, p.95 (1977). Link
  7. ^ The chemistry of diazonium and diazo groups. Part 1. Patai, Saul., Wiley InterScience (Online service). Chichester: Wiley. 1978. ISBN 978-0-470-77154-9. OCLC 501316965.{{cite book}}: CS1 maint: others (link)
  8. ^ Organic Syntheses, Coll. Vol. 6, p.392 (1988); Vol. 50, p.27 (1970). Link
  9. ^ Organic Syntheses, Coll. Vol. 5, p.258 (1973); Vol. 49, p.22 (1969). Link
  10. ^ Organic Syntheses, Coll. Vol. 7, p.438 (1990); Vol. 64, p.207 (1986).http://www.orgsyn.org/orgsyn/prep.asp?prep=CV7P0438
  11. ^ Lei, X.; Porco Ja, J. (2006). "Total synthesis of the diazobenzofluorene antibiotic (-)-kinamycin C1". Journal of the American Chemical Society. 128 (46): 14790–14791. doi:10.1021/ja066621v. PMID 17105273.
  12. ^ Elusive Natural Product Is Synthesized Stu Borman Chemical & Engineering News October 31, 2006 Link Archived 2008-08-28 at the Wayback Machine.
  13. ^ Example Organic Syntheses, Coll. Vol. 3, p.119 (1955); Vol. 26, p.13 (1946).Link
  14. ^ Shishkov, I. V.; Rominger, F.; Hofmann, P. (2009). "Remarkably Stable Copper(I) α-Carbonyl Carbenes: Synthesis, Structure, and Mechanistic Studies of Alkene Cyclopropanation Reactions". Organometallics. 28 (4): 1049–1059. doi:10.1021/om8007376.
  15. ^ M. Regitz, Angew. Chem., 79, 786 (1967); Angew. Chem. Intern. Ed. Engl., 6, 733 (1967).
  16. ^ a b Kurti Laszlo (2005). Strategic Applications of Named Reactions in Organic Synthesis. Czako Barbara. Burlington: Elsevier Science. ISBN 978-0-08-057541-4. OCLC 850164343.
  17. ^ Maas, Gerhard (2009-10-19), "New Syntheses of Diazo Compounds", Angewandte Chemie International Edition, vol. 48, no. 44, pp. 8186–8195, doi:10.1002/anie.200902785
  18. ^ Organic Syntheses, Coll. Vol. 5, p.179 (1973); Vol. 48, p.36 (1968). Link
  19. ^ Organic Syntheses, Coll. Vol. 6, p.414 (1988); Vol. 59, p.66 (1979). Link
  20. ^ Huw M. L. Davies; Wen-hao Hu; Dong Xing (2015). "Methyl Phenyldiazoacetate". EEROS: 1–10. doi:10.1002/047084289X.rn00444.pub2. ISBN 978-0-470-84289-8.
  21. ^ Selvaraj, Ramajeyam; Chintala, Srinivasa R.; Taylor, Michael T.; Fox, Joseph M. (2014). "3-Hydroxymethyl-3-phenylcyclopropene". Org. Synth. 91: 322. doi:10.15227/orgsyn.091.0322.
  22. ^ Taber, Douglass F.; Bai, Sha; Guo, Peng-fei (November 2008), "A convenient reagent for aldehyde to alkyne homologation", Tetrahedron Letters, vol. 49, no. 48, pp. 6904–6906, doi:10.1016/j.tetlet.2008.09.114, PMC 2634292, PMID 19946355
  23. ^ A Phosphine-Mediated Conversion of Azides into Diazo Compounds Eddie L. Myers and Ronald T. Raines Angew. Chem. Int. Ed. 2009, 48, 2359 –2363 doi:10.1002/anie.200804689
  24. ^ Organic Syntheses, Coll. Vol. 6, p.913 (1988); Vol. 50, p.94 (1970).Link
  25. ^ Hagihara, Ryota; Katsuyama, Yohei; Sugai, Yoshinori; Onaka, Hiroyasu; Ohnishi, Yasuo (2018). "Novel desferrioxamine derivatives synthesized using the secondary metabolism-specific nitrous acid biosynthetic pathway in Streptomyces davawensis". J. Antibiot. 71 (11): 911–919. doi:10.1038/s41429-018-0088-1. PMID 30120394.
Retrieved from "https://en.wikipedia.org/w/index.php?title=Diazo&oldid=1284912203"