View source for Diazo

{{short description|1=Chemical group (>C=N=N)}}
{{About||a discussion of copiers using the diazo process|whiteprint|the software|Diazo (software)}}

[[File:DiazoResonance.svg|300px|right|Diazo compounds have two main Lewis structures in resonance: R<sub>2</sub>>C<sup>−</sup>–N<sup>+</sup>≡N and R<sub>2</sub>>CH=N<sup>+</sup>=N<sup>−</sup>]]

In [[organic chemistry]], the '''diazo group''' is an organic [[moiety (chemistry)|moiety]] consisting of two linked [[nitrogen]] atoms at the terminal position.  Overall charge-neutral [[organic compound]]s containing the diazo group bound to a [[carbon]] atom are called '''diazo compounds''' or '''diazoalkanes'''{{efn|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).}} and are described by the general [[structural formula]] {{chem2|R2C\dN+\dN-}}. The simplest example of a diazo compound is [[diazomethane]], {{chem2|CH2N2}}.  Diazo compounds ({{chem2|R2C\dN2}}) should not be confused with [[azo compound]]s ({{chem2|R\sN\dN\sR}}) or with [[diazonium compound]]s ({{chem2|R\sN2+}}).

== 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-dipole]]s.  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<sub>2</sub>CHCOOEt). A group of isomeric compounds with only few similar properties are the [[diazirine]]s, where the carbon and two nitrogens are linked as a ring.

Four [[resonance structures]] can be drawn:<ref>F.A. Carey R.J. Sundberg ''Advanced Organic Chemistry'', 2nd Edition</ref>

:[[File:Diazo resonance structures.svg|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 ==
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."<ref>Trevor I. Williams, 'Griess, (Johann) Peter (1829–1888)', [[Oxford Dictionary of National Biography]], Oxford University Press, 2004</ref><ref>Peter Griess (1858) [http://babel.hathitrust.org/cgi/pt?id=njp.32101044011037;view=1up;seq=541 "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.</ref>

== Synthesis ==
Several methods exist for the preparation of diazo compounds.<ref>{{JerryMarch}}</ref><ref>''New Syntheses of Diazo Compounds'' Gerhard Maas [[Angew. Chem. Int. Ed.]] '''2009''', 48, 8186 – 8195 {{doi|10.1002/anie.200902785}}</ref>

=== From amines or nitrosamines ===
Alkyl-acyl [[nitrosamine]]s in base [[dehydration reaction|dehydrate]] to diazo compounds:<ref>Example: Organic Syntheses, Coll. Vol. 6, p.981 (1988); Vol. 57, p.95 (1977). [http://www.orgsynth.org/orgsyn/pdfs/CV6P0981.pdf Link]</ref>
[[File:Diazo Synthesis.svg|thumb|center|upright=1.75|alt=Diazo synthesis from N-alkyl-N-nitroso compounds|The mechanism shown here is one possibility;<ref>{{Cite book|title=The chemistry of diazonium and diazo groups. Part 1|date=1978|publisher=Wiley|others=Patai, Saul., Wiley InterScience (Online service)|isbn=978-0-470-77154-9|location=Chichester|oclc=501316965}}</ref> 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 [[amine]]s R-CH<sub>2</sub>-NH<sub>2</sub> with an α acceptor (R = COOR, CN, CHO, COR)  directly generate a diazo compound in [[nitrous acid]].

=== From hydrazones ===
[[Hydrazone]]s are [[organic oxidation|oxidized]] ([[dehydrogenation]]) for example with [[silver oxide]] or [[mercury oxide]] for example the synthesis of {{ill|2-diazopropane|fr}} from [[acetone hydrazone]].<ref>Organic Syntheses, Coll. Vol. 6, p.392 (1988); Vol. 50, p.27 (1970). [http://www.orgsyn.org/demo.aspx?prep=CV6P0392 Link]</ref> Other oxidizing reagents are [[lead tetraacetate]], [[manganese dioxide]] and the [[Swern reagent]]. [[Tosyl hydrazone]]s RRC=N-NHTs are reacted with base for example [[triethylamine]] in the synthesis of crotyl diazoacetate<ref>Organic Syntheses, Coll. Vol. 5, p.258 (1973); Vol. 49, p.22 (1969). [http://www.orgsyn.org/orgsyn/prep.asp?prep=CV5P0258 Link]</ref> and in the synthesis of [[phenyldiazomethane]] from PhCHNHTs and [[sodium methoxide]].<ref>Organic Syntheses, Coll. Vol. 7, p.438 (1990); Vol. 64, p.207 (1986).http://www.orgsyn.org/orgsyn/prep.asp?prep=CV7P0438</ref>

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:<ref>{{Cite journal| last1 = Lei | first1 = X.| last2 = Porco Ja | first2 = J.| title = Total synthesis of the diazobenzofluorene antibiotic (-)-kinamycin C1| journal = Journal of the American Chemical Society| volume = 128| issue = 46| pages = 14790–14791| year = 2006| pmid = 17105273 | doi = 10.1021/ja066621v}}</ref><ref>''Elusive Natural Product Is Synthesized'' Stu Borman [[Chemical & Engineering News]] October 31, 2006 [http://pubs.acs.org/cen/news/84/i45/8445notw4.html Link] {{Webarchive|url=https://web.archive.org/web/20080828122002/http://pubs.acs.org/cen/news/84/i45/8445notw4.html |date=2008-08-28 }}.</ref>
:[[File:KinamycinCSynthesis.png|400px|Kinamycin C synthesis]]

=== From diazomethyl compounds ===
An example of an [[electrophilic substitution]] using a diazomethyl compound is the [[Nierenstein reaction]] between an [[acyl halide]] and [[diazomethane]].<ref>Example [[Organic Syntheses]], Coll. Vol. 3, p.119 (1955); Vol. 26, p.13 (1946).[http://www.orgsynth.org/orgsyn/pdfs/CV3P0119.pdf Link]</ref>  The same reaction is the first step in the [[Arndt-Eistert synthesis]].

=== By diazo transfer ===
[[File:DOXGON.png|thumb|left|Solid state structure of the diazo compound t-BuO<sub>2</sub>CC(N<sub>2</sub>)C<sub>6</sub>H<sub>4</sub>NO<sub>2</sub>.  Key distances: C-N = 1.329 Å, N-N = 1.121 Å.<ref>{{cite journal|author=Shishkov, I. V.|author2=Rominger, F.|author3=Hofmann, P.|title=Remarkably Stable Copper(I) α-Carbonyl Carbenes: Synthesis, Structure, and Mechanistic Studies of Alkene Cyclopropanation Reactions|journal=Organometallics|year=2009 |volume=28|issue=4|pages=1049–1059|doi=10.1021/om8007376}}</ref>]]
In '''diazo transfer''', sometimes called '''Regitz diazo transfer''', certain [[carbon acid]]s react with [[sulfonyl azide]]s and a weak base like [[triethylamine]] or [[1,8-Diazabicyclo(5.4.0)undec-7-ene|DBU]], with corresponding [[sulfonamide]] byproduct.<ref>M. Regitz, Angew. Chem., 79, 786 (1967); Angew. Chem. Intern. Ed. Engl., 6, 733 (1967).</ref> The mechanism involves [[enolate]] attack at the terminal nitrogen, proton transfer, and sulfonamide anion expulsion.<ref name=KCStrat/>  
[[File:Regitz.png|center|frameless|450x450px|alt=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]], {{ill|4-Acetamidobenzenesulfonyl azide|lt=''p''{{nbh}}acetanilide&shy;sulfonyl azide|de|4-Acetamidobenzolsulfonylazid}}, and [[methanesulfonyl azide]].<ref>{{citation|first=Gerhard |last=Maas |date=2009-10-19 |doi=10.1002/anie.200902785 |issue=44 |pages=8186–8195 |periodical=Angewandte Chemie International Edition |title=New Syntheses of Diazo Compounds |volume=48}}<!-- auto-translated from German by Module:CS1 translator --></ref>  β-Carbonyl aldehydes undergo a [[decarbonylation|deformylative]] variant to give primary diazo compounds stabilized by only the [[ketone]].<ref name=KCStrat>{{Cite book|title=Strategic Applications of Named Reactions in Organic Synthesis|author=Kurti Laszlo|date=2005|publisher=Elsevier Science|others=Czako Barbara|isbn=978-0-08-057541-4|location=Burlington|oclc=850164343}}</ref>

Simple examples synthesize tert-butyl diazoacetate,<ref>Organic Syntheses, Coll. Vol. 5, p.179 (1973); Vol. 48, p.36 (1968). [http://www.orgsyn.org/orgsyn/prep.asp?prep=cv5p0179 Link]</ref> diazomalonate,<ref>Organic Syntheses, Coll. Vol. 6, p.414 (1988); Vol. 59, p.66 (1979). [http://www.orgsyn.org/orgsyn/prep.asp?prep=cv6p0414 Link]</ref>  or [[methyl phenyldiazoacetate]] (from [[methyl phenylacetate]]).<ref>{{cite journal|title=Methyl Phenyldiazoacetate|author=Huw M. L. Davies|author2=Wen-hao Hu|author3=Dong Xing|journal=EEROS|pages=1–10|doi=10.1002/047084289X.rn00444.pub2|year=2015|isbn=978-0-470-84289-8}}</ref><ref>{{cite journal|title=3-Hydroxymethyl-3-phenylcyclopropene|first1=Ramajeyam|last1=Selvaraj|first2=Srinivasa R.|last2=Chintala|first3=Michael T.|last3=Taylor|first4=Joseph M.|last4=Fox|journal=Org. Synth.|year=2014|volume=91|page=322|doi=10.15227/orgsyn.091.0322}}</ref>  

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 [[Seyferth–Gilbert_homologation#Bestmann_modification|Ohira-Bestmann reagent]] but is significantly more expensive.<ref>{{citation|first1=Douglass F. |last1=Taber |first2=Sha |last2=Bai |first3=Peng-fei |last3=Guo |date=November 2008 |doi=10.1016/j.tetlet.2008.09.114 |issue=48 |pages=6904–6906 |periodical=Tetrahedron Letters |pmc=2634292 |pmid=19946355 |title=A convenient reagent for aldehyde to alkyne homologation |volume=49}}<!-- auto-translated from German by Module:CS1 translator --></ref>

=== From azides ===
One method is described for the synthesis of diazo compounds from [[azide]]s using [[phosphines]]:<ref>''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}}</ref>
:[[File:AzidetoDiazo Myers 2009.svg|Azide to diazo conversion]]

== Reactions ==

=== In cycloadditions ===
Diazo compounds react as 1,3-dipoles in [[diazoalkane 1,3-dipolar cycloaddition]]s.

=== As carbene precursors ===
Diazo compounds are used as precursors to [[carbene]]s, which are generated by [[thermolysis]] or [[photolysis]], for example in the [[Wolff rearrangement]]. (In this regard, they resemble [[diazirene]]s.)  As such they are used in [[cyclopropanation]] for example in the reaction of [[ethyl diazoacetate]] with [[styrene]].<ref>Organic Syntheses, Coll. Vol. 6, p.913 (1988); Vol. 50, p.94 (1970).[http://www.orgsyn.org/orgsyn/prep.asp?prep=CV6P0913 Link]</ref> Certain diazo compounds can couple to form [[alkene]]s in a formal [[carbene dimerization]] reaction.

Diazo compounds are intermediates in the [[Bamford–Stevens reaction]] of [[tosylhydrazone]]s to alkenes, again with a carbene intermediate:
:[[File:Bamford-Stevens reaction mechanism.svg|550px|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 ===
The '''Buchner-Curtius-Schlotterbeck reaction''' yields ketones from aldehydes and aliphatic diazo compounds:
:[[File:Buchner-Curtius-Schlotterbeck Reaction.svg|400px|Buchner-Curtius-Schlotterbeck reaction]]
The reaction type is [[nucleophilic addition]].

== Occurrence in nature ==
Several families of naturally occurring products feature the diazo group. The [[kinamycin]]s and [[lomaiviticin]] are [[DNA intercalation|DNA intercalating]] molecules, with the diazo functionality as their "warheads". In the presence of a [[reducing agent]], loss of N<sub>2</sub> occurs to generate a DNA-cleaving [[fluorenyl]] radical.

One [[biochemical]] process for diazo formation is the <small>L</small>-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 [[Sequence homology|homologous]] genes appear widespread in [[actinobacteria]].<ref>{{cite journal |journal= J. Antibiot. |year= 2018 |volume= 71 |issue= 11 |pages= 911–919 |doi= 10.1038/s41429-018-0088-1 |title= Novel desferrioxamine derivatives synthesized using the secondary metabolism-specific nitrous acid biosynthetic pathway in ''Streptomyces davawensis'' |first1= Ryota |last1= Hagihara |first2= Yohei |last2= Katsuyama |first3= Yoshinori |last3= Sugai |first4= Hiroyasu |last4= Onaka |first5= Yasuo |last5= Ohnishi |pmid= 30120394 |doi-access= free }}</ref>

== See also ==
* [[Fluorosulfonyl azide]]
* [[Reprography]]
* [[Whiteprint]]

== Notes ==
{{notelist|30em}}

== References ==
{{Reflist}}

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[[Category:Functional groups]]
[[Category:Diazo compounds| ]]