Diazo

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Diazo compounds have two main Lewis structures in resonance: R2>C -N [?]N and R2>CH=N =N DiazoResonance.svg
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 [lower-alpha 1] 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).

Contents

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 (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.svg

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." [2] [3]

Synthesis

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

From amines

Alpha-acceptor-substituted primary aliphatic amines R-CH2-NH2 (R = COOR, CN, CHO, COR) react with nitrous acid to generate the diazo compound.

From diazomethyl compounds

An example of an electrophilic substitution using a diazomethyl compound is that of a reaction between an acyl halide and diazomethane, [6] for example the first step in the Arndt-Eistert synthesis.

By diazo transfer

In diazo transfer certain carbon acids react with tosyl azide in the presence of a weak base like triethylamine or DBU. The byproduct is the corresponding tosylamide (p-toluenesulfonamide). This reaction is also called the Regitz diazo transfer. [7] Examples are the synthesis of tert-butyl diazoacetate [8] and diazomalonate. [9] Methyl phenyldiazoacetate is generated in this way by treating methyl phenylacetate with p-acetamidobenzenesulfonyl azide in the presence of base. [10] [11]

Solid state structure of the diazo compound t-BuO2CC(N2)C6H4NO2. Key distances: C-N = 1.329 A, N-N = 1.121 A. DOXGON.png
Solid state structure of the diazo compound t-BuO2CC(N2)C6H4NO2. Key distances: C-N = 1.329 Å, N-N = 1.121 Å.

The mechanism involves attack of the enolate at the terminal nitrogen, proton transfer, and expulsion of the anion of the sulfonamide. Use of the β-carbonyl aldehyde leads to a deformylative variant of the Regitz transfer, which is useful for the preparation of diazo compounds stabilized by only one carbonyl group. [13]

Regitz.png

From N-alkyl-N-nitroso compounds

Diazo compounds can be obtained in an elimination reaction of N-alkyl-N-nitroso compounds, [14] such as in the synthesis of diazomethane from Diazald or MNNG:

Diazo Synthesis.svg

(The mechanism shown here is one possibility. [15] For an alternative mechanism for the analogous formation of diazomethane from an N-nitrososulfonamide, see the page on Diazald.)

From hydrazones

Hydrazones are oxidized (dehydrogenation) for example with silver oxide or mercury oxide for example the synthesis of 2-diazopropane  [ fr ] from acetone hydrazone. [16] 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 [17] and in the synthesis of phenyldiazomethane from PhCHNHTs and sodium methoxide. [18]

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: [19] [20]

KinamycinCSynthesis.png

From azides

One method is described for the synthesis of diazo compounds from azides using phosphines: [21]

AzidetoDiazo Myers 2009.svg

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 carbenes, which are generated by thermolysis or photolysis, for example in the Wolff rearrangement. As such they are used in cyclopropanation for example in the reaction of ethyl diazoacetate with styrene. [22] 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 mechanism.svg

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:

Buchner-Curtius-Schlotterbeck Reaction.svg

The reaction type is nucleophilic addition.

Occurrence in nature

Two families of naturally occurring products feature the diazo group: kinamycin and lomaiviticin. These molecules are DNA-intercalators, with diazo functionality as their "warheads". Loss of N2, induced reductively, generates a DNA-cleaving fluorenyl radical.

See also

Notes

  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).

Related Research Articles

<span class="mw-page-title-main">Hydrazone</span> Organic compounds - Hydrazones

Hydrazones are a class of organic compounds with the structure R1R2C=N−NH2. They are related to ketones and aldehydes by the replacement of the oxygen =O with the =N−NH2 functional group. They are formed usually by the action of hydrazine on ketones or aldehydes.

An ylide or ylid is a neutral dipolar molecule containing a formally negatively charged atom (usually a carbanion) directly attached to a heteroatom with a formal positive charge (usually nitrogen, phosphorus or sulfur), and in which both atoms have full octets of electrons. The result can be viewed as a structure in which two adjacent atoms are connected by both a covalent and an ionic bond; normally written X+–Y−. Ylides are thus 1,2-dipolar compounds, and a subclass of zwitterions. They appear in organic chemistry as reagents or reactive intermediates.

In organic chemistry, a carbene is a molecule containing a neutral carbon atom with a valence of two and two unshared valence electrons. The general formula is R−:C−R' or R=C: where the R represents substituents or hydrogen atoms.

The 1,3-dipolar cycloaddition is a chemical reaction between a 1,3-dipole and a dipolarophile to form a five-membered ring. The earliest 1,3-dipolar cycloadditions were described in the late 19th century to the early 20th century, following the discovery of 1,3-dipoles. Mechanistic investigation and synthetic application were established in the 1960s, primarily through the work of Rolf Huisgen. Hence, the reaction is sometimes referred to as the Huisgen cycloaddition. 1,3-dipolar cycloaddition is an important route to the regio- and stereoselective synthesis of five-membered heterocycles and their ring-opened acyclic derivatives. The dipolarophile is typically an alkene or alkyne, but can be other pi systems. When the dipolarophile is an alkyne, aromatic rings are generally produced.

<span class="mw-page-title-main">Bamford–Stevens reaction</span> Synthesis of alkenes by base-catalysed decomposition of tosylhydrazones

The Bamford–Stevens reaction is a chemical reaction whereby treatment of tosylhydrazones with strong base gives alkenes. It is named for the British chemist William Randall Bamford and the Scottish chemist Thomas Stevens Stevens (1900–2000). The usage of aprotic solvents gives predominantly Z-alkenes, while protic solvent gives a mixture of E- and Z-alkenes. As an alkene-generating transformation, the Bamford–Stevens reaction has broad utility in synthetic methodology and complex molecule synthesis.

<span class="mw-page-title-main">Diazonium compound</span> Group of organonitrogen compounds

Diazonium compounds or diazonium salts are a group of organic compounds sharing a common functional group [R−N+≡N]X− where R can be any organic group, such as an alkyl or an aryl, and X is an inorganic or organic anion, such as a halide.

In organic chemistry, the Arndt–Eistert reaction is the conversion of a carboxylic acid to its homologue. Named for the German chemists Fritz Arndt (1885–1969) and Bernd Eistert (1902–1978), the method entails treating an acid chlorides with diazomethane. It is a popular method of producing β-amino acids from α-amino acids.

The Barton–Kellogg reaction is a coupling reaction between a diazo compound and a thioketone, giving an alkene by way of an episulfide intermediate. The Barton–Kellogg reaction is also known as Barton–Kellogg olefination and Barton olefin synthesis.

<span class="mw-page-title-main">Hydrazone iodination</span> Chemical reaction

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 Derek Barton in 1962 the reaction is sometimes referred to as the Barton reaction or, more descriptively, as the Barton vinyl iodine procedure.

α-Halo ketone

In organic chemistry, an α-halo ketone is a functional group consisting of a ketone group or more generally a carbonyl group with an α-halogen substituent. α-Halo ketones are alkylating agents. Prominent α-halo ketones include phenacyl bromide and chloroacetone.

In organic chemistry, umpolung or polarity inversion is the chemical modification of a functional group with the aim of the reversal of polarity of that group. This modification allows secondary reactions of this functional group that would otherwise not be possible. The concept was introduced by D. Seebach and E.J. Corey. Polarity analysis during retrosynthetic analysis tells a chemist when umpolung tactics are required to synthesize a target molecule.

<span class="mw-page-title-main">Wolff rearrangement</span>

The Wolff rearrangement is a reaction in organic chemistry in which an α-diazocarbonyl compound is converted into a ketene by loss of dinitrogen with accompanying 1,2-rearrangement. The Wolff rearrangement yields a ketene as an intermediate product, which can undergo nucleophilic attack with weakly acidic nucleophiles such as water, alcohols, and amines, to generate carboxylic acid derivatives or undergo [2+2] cycloaddition reactions to form four-membered rings. The mechanism of the Wolff rearrangement has been the subject of debate since its first use. No single mechanism sufficiently describes the reaction, and there are often competing concerted and carbene-mediated pathways; for simplicity, only the textbook, concerted mechanism is shown below. The reaction was discovered by Ludwig Wolff in 1902. The Wolff rearrangement has great synthetic utility due to the accessibility of α-diazocarbonyl compounds, variety of reactions from the ketene intermediate, and stereochemical retention of the migrating group. However, the Wolff rearrangement has limitations due to the highly reactive nature of α-diazocarbonyl compounds, which can undergo a variety of competing reactions.

<span class="mw-page-title-main">Cyclopropanation</span> Chemical process which generates cyclopropane rings

In organic chemistry, cyclopropanation refers to any chemical process which generates cyclopropane rings. It is an important process in modern chemistry as many useful compounds bear this motif; for example pyrethroid insecticides and a number of quinolone antibiotics. However, the high ring strain present in cyclopropanes makes them challenging to produce and generally requires the use of highly reactive species, such as carbenes, ylids and carbanions. Many of the reactions proceed in a cheletropic manner.

<span class="mw-page-title-main">Nierenstein reaction</span>

The Nierenstein reaction is an organic reaction describing the conversion of an acid chloride into a haloketone with diazomethane. It is an insertion reaction in that the methylene group from the diazomethane is inserted into the carbon-chlorine bond of the acid chloride.

Electrophilic amination is a chemical process involving the formation of a carbon–nitrogen bond through the reaction of a nucleophilic carbanion with an electrophilic source of nitrogen.

An insertion reaction is a chemical reaction where one chemical entity interposes itself into an existing bond of typically a second chemical entity e.g.:

Carbene dimerization is a type of organic reaction in which two carbene or carbenoid precursors react in a formal dimerization to an alkene. This reaction is often considered an unwanted side-reaction but it is also investigated as a synthetic tool. In this reaction type either the two carbenic intermediates react or a carbenic intermediate reacts with a carbene precursor. An early pioneer was Christoph Grundmann reporting on a carbene dimerisation in 1938. In the domain of persistent carbenes the Wanzlick equilibrium describes an equilibrium between a carbene and its alkene.

A tosylhydrazone in organic chemistry is a functional group with the general structure RR'C=N-NH-Ts where Ts is a tosyl group. Organic compounds having this functional group can be accessed by reaction of an aldehyde or ketone with tosylhydrazine.

The Buchner–Curtius–Schlotterbeck reaction is the reaction of aldehydes or ketones with aliphatic diazoalkanes to form homologated ketones. It was first described by Eduard Buchner and Theodor Curtius in 1885 and later by Fritz Schlotterbeck in 1907. Two German chemists also preceded Schlotterbeck in discovery of the reaction, Hans von Pechmann in 1895 and Viktor Meyer in 1905. The reaction has since been extended to the synthesis of β-keto esters from the condensation between aldehydes and diazo esters. The general reaction scheme is as follows:

An organic azide is an organic compound that contains an azide functional group. Because of the hazards associated with their use, few azides are used commercially although they exhibit interesting reactivity for researchers. Low molecular weight azides are considered especially hazardous and are avoided. In the research laboratory, azides are precursors to amines. They are also popular for their participation in the "click reaction" between an azide and an alkyne and in Staudinger ligation. These two reactions are generally quite reliable, lending themselves to combinatorial chemistry.

References

  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 edition, 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. 3, p.119 (1955); Vol. 26, p.13 (1946).Link
  7. ↑ M. Regitz, Angew. Chem., 79, 786 (1967); Angew. Chem. Intern. Ed. Engl., 6, 733 (1967).
  8. ↑ Organic Syntheses, Coll. Vol. 5, p.179 (1973); Vol. 48, p.36 (1968). Link
  9. ↑ Organic Syntheses, Coll. Vol. 6, p.414 (1988); Vol. 59, p.66 (1979). Link
  10. ↑ 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.
  11. ↑ 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.
  12. ↑ 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.
  13. ↑ Kurti, Laszlo (2005). Strategic Applications of Named Reactions in Organic Synthesis : Background and Detailed Mechanisms. Czako, Barbara. Burlington: Elsevier Science. ISBN   978-0-08-057541-4. OCLC   850164343.
  14. ↑ Example: Organic Syntheses, Coll. Vol. 6, p.981 (1988); Vol. 57, p.95 (1977). Link
  15. ↑ 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)
  16. ↑ Organic Syntheses, Coll. Vol. 6, p.392 (1988); Vol. 50, p.27 (1970). Link
  17. ↑ Organic Syntheses, Coll. Vol. 5, p.258 (1973); Vol. 49, p.22 (1969). Link
  18. ↑ Organic Syntheses, Coll. Vol. 7, p.438 (1990); Vol. 64, p.207 (1986).http://www.orgsyn.org/orgsyn/prep.asp?prep=CV7P0438
  19. ↑ 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.
  20. ↑ Elusive Natural Product Is Synthesized Stu Borman Chemical & Engineering News October 31, 2006 Link Archived 2008-08-28 at the Wayback Machine .
  21. ↑ 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
  22. ↑ Organic Syntheses, Coll. Vol. 6, p.913 (1988); Vol. 50, p.94 (1970).Link
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