Persistent carbene

{{Short description|Type of carbene demonstrating particular stability}} [[File:SIMes.png|thumb|300px|1,3-Dimesityl-imidazol-4,5-dihydro-2-ylidene, a representative persistent carbene]] A '''persistent carbene''' (also known as '''stable carbene''') is an organic molecule whose natural resonance structure has a carbon atom with incomplete octet (a carbene), but does not exhibit the tremendous instability typically associated with such moieties. The best-known examples and by far largest subgroup are the '''''N''-heterocyclic carbenes''' (NHC)<ref name="Hopkinson-2014">{{cite journal |author1=Hopkinson, M. N. |author2=Richter, C. |author3=Schedler, M. |author4=Glorius, F. |year=2014 |title=An Overview of ''N''-Heterocyclic Carbenes |journal=Nature |volume=510 |issue=7506 |pages=485–496 |bibcode=2014Natur.510..485H |doi=10.1038/nature13384 |pmid=24965649 |s2cid=672379}}</ref> (sometimes called '''Arduengo carbenes'''), in which nitrogen atoms flank the formal carbene.

Modern theoretical analysis suggests that the term "persistent carbene" is in fact a misnomer. Persistent carbenes do not in fact have a carbene electronic structure in their ground state, but instead an ylide stabilized by aromatic resonance or steric shielding. Acid catalyzes the carbene-like dimerization that some persistent carbenes undergo over the course of days.

Persistent carbenes in general, and Arduengo carbenes in particular, are popular ligands in organometallic chemistry.

==History==

===Early evidence=== In 1957, Ronald Breslow proposed that a relatively stable nucleophilic carbene, a thiazol-2-ylidene derivative of vitamin B₁ (thiamine), was the catalyst involved in the benzoin condensation that yields furoin from furfural.<ref name=Breslow2>{{cite journal |title = Mechanism of Thiamine Action: Participation of a Thiazolium Zwitterion |author = Ronald Breslow |journal=Chem. Ind. |volume = 26 |pages = 893 |year = 1957}}</ref><ref>{{cite journal | author = Ronald Breslow| year = 1958 | title = On the Mechanism of Thiamine Action. IV.1 Evidence from Studies on Model Systems | journal =J. Am. Chem. Soc. | volume = 80 | issue = 14| pages = 3719–3726 | doi = 10.1021/ja01547a064| bibcode = 1958JAChS..80.3719B }}</ref> In this cycle, the vitamin's thiazolium ring exchanges a hydrogen atom (attached to carbon 2 of the ring) for a furfural residue. In deuterated water, the C2-proton was found to rapidly exchange for a deuteron in a statistical equilibrium:<ref name=Breslow3>{{cite journal |title = Rapid Deuterium Exchange in Thiazolium Salts |author = R. Breslow |journal =J. Am. Chem. Soc. |volume = 79 |issue = 7|pages = 1762–1763 |year = 1957 |doi = 10.1021/ja01564a064|bibcode = 1957JAChS..79.1762B }}</ref> center|600px|Deuterium exchange of the C2-proton of thiazolium salt.|frameless

This exchange was proposed to proceed via intermediacy of a thiazol-2-ylidene. In 2012 the isolation of the so-called ''Breslow intermediate'' was reported.<ref>{{cite journal |author1=Berkessel A. |author2=Elfert S. |author3=Yatham V. R. |author4=Neudörfl J.-M. |author5=Schlörer N. E. |author6=Teles J. H. | year = 2012 | title = Umpolung by ''N''-Heterocyclic Carbenes: Generation and Reactivity of the Elusive 2,2-Diamino Enols (Breslow Intermediates)| journal =Angew. Chem. Int. Ed. | volume = 51| issue = 49| pages = 12370–12374| doi = 10.1002/anie.201205878 |pmid=23081675|doi-access=free }}</ref><ref>[http://cen.acs.org/articles/90/i44/Chemists-Approach-Elusive-Breslow-Intermediate.html Chemists Approach Elusive Breslow Intermediate Carmen Drahl]</ref>

In 1960, Hans-Werner Wanzlick and coworkers conjectured that carbenes derived from dihydroimidazol-2-ylidene were produced by vacuum pyrolysis of the corresponding 2-trichloromethyl dihydroimidazole compounds with the loss of chloroform.<ref name=Wanzlick1>{{cite journal|title = Ein neuer Zugang zur Carben-Chemie |trans-title=A new way into carbene chemistry |author1=Hans-Werner Wanzlick |author2=E. Schikora |journal=Angew. Chem. |volume = 72 |issue = 14 |pages = 494|year = 1960 |doi = 10.1002/ange.19600721409|bibcode=1960AngCh..72..494W }}</ref><ref name=Wanzlick2>{{cite journal |title = Ein nucleophiles Carben |trans-title=A nucleophilic carbene |author1=H. W. Wanzlick |author2=E. Schikora |journal =Chem. Ber. |volume = 94 |issue = 9 |pages = 2389–2393 |year = 1960 |doi = 10.1002/cber.19610940905}}</ref> <ref name=Wanzlick3>{{cite journal|author = H. W. Wanzlick|journal = Angew. Chem. Int. Ed.|year = 1962|volume = 1|pages = 75–80|doi = 10.1002/anie.196200751|title = Aspects of Nucleophilic Carbene Chemistry|issue = 2}}</ref> They conjectured that the carbene existed in equilibrium with its dimer, a tetraaminoethylene derivative, the so-called Wanzlick equilibrium. This conjecture was challenged by Lemal and coworkers in 1964, who presented evidence that the dimer did not dissociate;<ref name=Lemal1>{{cite journal|author1=D. M. Lemal |author2=R. A. Lovald |author3=K. I. Kawano |title = Tetraaminoethylenes. The Question of Dissociation| journal=J. Am. Chem. Soc.| year=1964 |volume=86 |pages=2518–2519 |doi=10.1021/ja01066a044|issue = 12|bibcode=1964JAChS..86.2518L }}</ref> and by Winberg in 1965.<ref name=Winberg1>{{cite journal|author1=H. E. Winberg |author2=J. E. Carnahan |author3=D. D. Coffman |author4=M. Brown |title = Tetraaminoethylenes |journal=J. Am. Chem. Soc. |year=1965 |volume=87 |pages=2055–2056 |doi=10.1021/ja01087a040 |issue=9|bibcode=1965JAChS..87.2055W }}</ref> However, subsequent experiments by Denk, Herrmann and others have confirmed this equilibrium, albeit in specific circumstances.<ref name=denk99>{{cite journal |author1=Denk M. K. |author2=Hatano K. |author3=Ma M. | year = 1999 | title = Nucleophilic Carbenes and the Wanzlick Equilibrium A Reinvestigation | journal =Tetrahedron Lett. | volume = 40 | issue = 11| pages = 2057–2060 | doi = 10.1016/S0040-4039(99)00164-1}}</ref><ref>{{cite journal |author1=Böhm Volker P. W. |author2=Herrmann Wolfgang A. | year = 2000 | title = The Wanzlick Equilibrium | journal =Angew. Chem. Int. Ed. | volume = 39 | issue = 22| pages = 4036–4038 | doi = 10.1002/1521-3773(20001117)39:22<4036::AID-ANIE4036>3.0.CO;2-L|pmid=11093196 }}</ref>

===Isolation=== In 1970, Wanzlick's group generated imidazol-2-ylidene carbenes by the deprotonation of an imidazolium salt.<ref name="Wanzlick-1970">{{cite journal |author1=H. W. Wanzlick |author2=H. J. Schonherr |year=1970 |title=Chemie nucleophiler Carbene, XVIII, 1) 1.3.4.5-Tetraphenyl-imidazoliumperchlorat |trans-title=Chemistry of nucleophilic carbenes, XVIII. 1) 1,3,4,5-Tetraphenylimidazolium perchlorate |journal=Liebigs Ann. Chem. |volume=731 |pages=176–179 |doi=10.1002/jlac.19707310121}}</ref> Wanzlick as well as Roald Hoffmann,<ref name=Wanzlick3 /><ref>{{cite journal|author1=R. Gleiter |author2=R. Hoffmann |title = Stabilizing a singlet methylene |journal=J. Am. Chem. Soc. |year=1968 |volume=90| pages=5457–5460 |doi=10.1021/ja01022a023 |issue=20|bibcode=1968JAChS..90.5457G }}</ref> proposed that these imidazole-based carbenes should be more stable than their 4,5-dihydro analogues, due to Hückel-type aromaticity. Wanzlick did not however isolate imidazol-2-ylidenes, but instead their coordination compounds with mercury and isothiocyanate:<ref name="Wanzlick-1970" />

center|600px|Preparation and trapping of an imidazol-2-ylidene.|frameless

In 1988, Guy Bertrand and others isolated a phosphinocarbene. These species can be represented as either a λ³-phosphinocarbene or λ⁵-phosphaacetylene:<ref name=Bertrand4>{{cite journal|title = Analogous α,α{{prime}}-bis-carbenoid, triply bonded species: synthesis of a stable λ³-phosphino carbene-λ³-phosphaacetylene |author1=A. Igau |author2=H. Grutzmacher |author3=A. Baceiredo |author4=G. Bertrand |journal=J. Am. Chem. Soc. |volume=110 |pages=6463–6466 |year=1988 |issue=19 |doi=10.1021/ja00227a028}}</ref><ref name=Bertrand5>{{cite journal |title = λ³-Phosphinocarbenes λ⁵-phosphaacetylenes |author1=G. Bertrand |author2=R. Reed |journal=Coord. Chem. Rev. |volume=137 |pages=323–355 |year=1994 |doi=10.1016/0010-8545(94)03005-B}}</ref> center|600px|Alkyne and carbene resonances structures of Bertrand's carbene|frameless

These compounds were called "push-pull carbenes" in reference to the contrasting electron affinities of the phosphorus and silicon atoms, and exhibited both carbenic and alkynic reactivity; their electronic structure was (and would remain!) unclear. In 2000, Bertrand would obtain additional carbenes of the phosphanyl type, including (phosphanyl)(trifluoromethyl)carbene, stable in solution at -30&nbsp;°C.<ref>{{cite journal |author1=Christophe Buron |author2=Heinz Gornitzka |author3=Vadim Romanenko |author4=Guy Bertrand |year=2000 |title=Stable Versions of Transient Push-Pull Carbenes: Extending Lifetimes from Nanoseconds to Weeks |journal=Science |volume=288 |issue=5467 |pages=834–836 |bibcode=2000Sci...288..834B |doi=10.1126/science.288.5467.834 |pmid=10796999}}</ref>

In 1991, Arduengo and coworkers obtained the first crystalline diaminocarbene by deprotonation of an imidazolium cation:<ref name="Arduengo1">{{cite journal |author1=Arduengo, A.J. |author2=Harlow, R.L. |author3=Kline, M. |title=A stable crystalline carbene |year=1991 |journal=J. Am. Chem. Soc. |volume=113 |issue=1|pages=361–363 |doi=10.1021/ja00001a054|bibcode=1991JAChS.113..361A }}</ref>

center|600px|Preparation of ''N'',''{{prime|N}}''-diadamantyl-imidazol-2-ylidene|frameless

This carbene, heralding a large family of carbenes with the imidazol-2-ylidene core, is indefinitely stable at room temperature in the absence of oxygen and moisture, and melts at 240–241&nbsp;°C without decomposition.

The first air-stable Arduengo carbene, a chlorinated member of the imidazol-2-ylidene family, was obtained in 1997.<ref name="Arduengo5" />

===New examples and new theory=== [[file:AllylMO.png|left|120px|thumb|MO's of the allylic system.]] In the modern understanding, the superficially unoccupied ''p''-orbital on a stable carbene is not, in fact, fully empty. Instead, the carbene Lewis structures are in resonance with dative bonds toward adjacent lone-pair or π bond orbitals.<ref>{{Cite web |last=Rzepa |first=Henry |author-link=Henry Rzepa |date=11 Sep 2016 |title=What's in a name? Carbenes: a reality check. |url=https://www.ch.imperial.ac.uk/rzepa/blog/?p=16758 |access-date=15 Feb 2024 |website=Chemistry with a Twist}}</ref>

That persistent carbenes have ylidic character is hardly obvious, and indeed was initially contradicted. The X-ray structure of ''N'',''{{prime|N}}''-diadamantyl-imidazol-2-ylidene revealed longer N–C bond lengths in the ring of the carbene than in the parent imidazolium compound, suggesting very little double bond character to these bonds.<ref>{{cite journal |last1=Arduengo |first1=Anthony J. |last2=Harlow |first2=Richard L. |last3=Kline |first3=Michael |date=January 1991 |title=A stable crystalline carbene |journal=J. Am. Chem. Soc. |volume=113 |issue=1 |pages=361–363 |doi=10.1021/ja00001a054|bibcode=1991JAChS.113..361A }}</ref> Hence early workers attributed the stability of Arduengo carbenes to the bulky ''N''-adamantyl substituents, which prevent reaction with other molecules.{{Cn|date=June 2025}}

However, replacement of the ''N''-adamantyl groups with methyl groups also affords 1,3,4,5-tetramethylimidazol-2‑ylidene (Me₄ImC:), a thermodynamically stable unhindered NHC ([http://ajarduengo.net/Jmol/htmlfiles/0161Viewer.html 3D]):<ref name="Arduengo2" />

120px|1,3,4,5-tetramethyl&shy;imidazol-2-ylidene, a relatively unhindered carbene. |center|frameless left|thumb|120px|Bis(diisopropylamino) carbene, the first acyclic stable carbene. In 1995, Arduengo's group obtained a carbene derivative of dihydroimidazol-2-ylidene, proving that stability did not arise from the aromaticity of the conjugated imidazole backbone.<ref name="Arduengo3">{{cite journal |author1=J. Arduengo |author2=J. R. Goerlich |author3=W. J. Marshall |year=1995 |title=A stable diaminocarbene |journal=J. Am. Chem. Soc. |volume=117 |issue=44 |pages=11027–11028 |doi=10.1021/ja00149a034|bibcode=1995JAChS.11711027A }}</ref> The following year, the first acyclic persistent carbene demonstrated that stability did not require even cyclicity.<ref name="Alder1">{{cite journal |author1=R. W. Alder |author2=P. R. Allen |author3=M. Murray |author4=A. G. Orpen |year=1996 |title=Bis(diisopropylamino)carbene |journal=Angew. Chem. Int. Ed. |volume=35 |issue=10 |pages=1121–1123 |doi=10.1002/anie.199611211}}</ref>

Unhindered derivatives of the hydrogenated<ref name="Denk1">{{cite journal |author1=M. K. Denk |author2=A. Thadani |author3=K. Hatano |author4=A. J. Lough |year=1997 |title=Steric Stabilization of Nucleophilic Carbenes |journal=Angew. Chem. Int. Ed. |volume=36 |issue=23 |pages=2607–2609 |doi=10.1002/anie.199726071}}</ref><ref name="AlderEtDAC">{{cite journal |last1=Alder |first1=RW |last2=Chaker |first2=L |last3=Paolini |first3=FP |year=2004 |title=Bis(diethylamino)carbene and the mechanism of dimerisation for simple diaminocarbenes |journal=Chemical Communications |issue=19 |pages=2172–2173 |doi=10.1039/b409112d |pmid=15467857}}</ref> and acyclic<ref name="AlderEtDAC" /><ref name="Alder2">{{cite journal |author1=R. W. Alder |author2=M. E. Blake |year=1997 |title=Bis(''N''-piperidyl)carbene and its slow dimerisation to tetrakis(''N''-piperidyl)ethene |journal=Chem. Commun. |issue=16 |pages=1513–1514 |doi=10.1039/a703610h}}</ref><ref name="Alder3">{{cite journal |author1=R. W. Alder |author2=M. E. Blake |author3=J. M. Oliva |year=1999 |title=Diaminocarbenes; Calculation of Barriers to Rotation about C_carbene–N Bonds, Barriers to Dimerization, Proton Affinities, and ¹³C NMR Shifts |journal=J. Phys. Chem. A |volume=103 |issue=50 |pages=11200–11211 |bibcode=1999JPCA..10311200A |doi=10.1021/jp9934228}}</ref> carbenes dimerize over time, but proved key to resolving the electronic structure. Acyclic carbenes are flexible and bonds to the carbenic atom admit rotation. But bond rotation in the compound appeared hindered, suggesting that they did indeed have a double bond character.<ref name="Alder1" />

Subsequent research has focused on expanding the array of heteroatoms stabilizing the ylide. Most persistent carbenes are stabilized by two flanking nitrogen centers. The outliers include an aminothiocarbene and an aminooxycarbene ([http://ajarduengo.net/Jmol/htmlfiles/0165Viewer.html 3D])...<ref name="Arduengo4">{{cite journal |author=A. J. Arduengo, J. R. Goerlich and W. J. Marshall |year=1997 |title=A Stable Thiazol-2-ylidene and Its Dimer |journal=Liebigs Ann. Chem. |volume=1997 |issue=2 |pages=365–374 |doi=10.1002/jlac.199719970213}}</ref><ref name="Alder4">{{cite journal |author1=R. W. Alder |author2=C. P. Butts |author3=A. G. Orpen |year=1998 |title=Stable Aminooxy- and Aminothiocarbenes |journal=J. Am. Chem. Soc. |volume=120 |issue=44 |pages=11526–11527 |doi=10.1021/ja9819312|bibcode=1998JAChS.12011526A }}</ref> center|600px|Stable carbenes with oxygen or sulfur atoms bound to the carbenic atom |frameless...and room-temperature-stable bis(diisopropylamino)cyclopropenylidene, in which the amines are connected through vinylogy.<ref name="bertrand2006">{{cite journal |last1=Lavallo |first1=Vincent |last2=Canac |first2=Yves |last3=Donnadieu |first3=Bruno |last4=Schoeller |first4=Wolfgang W. |last5=Bertrand |first5=Guy |year=2006 |title=Cyclopropenylidenes: From Interstellar Space to an Isolated Derivative in the Laboratory |journal=Science |volume=312 |issue=5774 |pages=722–724 |bibcode=2006Sci...312..722L |doi=10.1126/science.1126675 |pmc=2427275 |pmid=16614171}}</ref> In 2000, Bertrand obtained a moderately stable (amino)(aryl)carbene with only one heteroatom adjacent to the carbenic atom.<ref>{{cite journal |last1=Solé |first1=Stéphane |last2=Gornitzka |first2=Heinz |last3=Schoeller |first3=Wolfgang W. |last4=Bourissou |first4=Didier |last5=Bertrand |first5=Guy |year=2001 |title=(Amino)(Aryl)Carbenes: Stable Singlet Carbenes Featuring a Spectator Substituent |journal=Science |volume=292 |issue=5523 |pages=1901–1903 |bibcode=2001Sci...292.1901S |doi=10.1126/science.292.5523.1901 |pmid=11397943}}</ref><ref>{{cite journal |author1=Lai Chun-Liang |author2=Guo Wen-Hsin |author3=Lee Ming-Tsung |author4=Hu Ching-Han |year=2005 |title=Ligand properties of ''N''-heterocyclic and Bertrand carbenes: A density functional study |journal=J. Organomet. Chem. |volume=690 |issue=24–25 |pages=5867–5875 |doi=10.1016/j.jorganchem.2005.07.058}}</ref> <!-- TO DO (?): * Triplet carbenes * Wanzlick equilibrium mechanism elucidation * Mesoionic carbenes -->

==Classes of stable carbenes== Stable carbenes rely on adjacent heteroatoms to stabilize the "carbenic" carbon. Stable carbenes can be usefully categorized by the number of such atoms that are nitrogen.

Carbenes that formally derive from imidazol-2-ylidenes by substitution of sulfur, oxygen, or other chalcogens for ''both'' α-nitrogens are expected to be unstable, as they have the potential to dissociate into an alkyne (R¹C≡CR²) and a carbon dichalcogenide (X¹=C=X²).{{original research inline|date=March 2026}} Evidence for the reverse process exists: carbon disulfide (CS₂) reacts with electron-deficient acetylene derivatives to conjecturally give transient 1,3-dithiolium carbenes (i.e. where X¹ = X² = S), which then dimerise to tetrathiafulvene derivatives.<ref name="Haztzler1970">{{cite journal |author=H. D. Haztzler |year=1970 |title=Nucleophilic 1,3-dithiolium carbenes |journal=J. Am. Chem. Soc. |volume=92 |issue=5 |pages=1412–1413 |doi=10.1021/ja00708a058|bibcode=1970JAChS..92.1412H }}</ref><ref name="Haztzler1972">{{cite journal |author=H. D. Hartzler |year=1972 |title=1,3-Dithiolium carbenes from acetylenes and carbon disulfide |journal=J. Am. Chem. Soc. |volume=95 |issue=13 |pages=4379–4387 |doi=10.1021/ja00794a039}}</ref>

=== Diaminocarbenes === A wide variety of bisazomethine ylides are known, both cyclic<ref name="Arduengo3" /><ref name="Denk1" /><ref name="Alder5">{{cite journal |author1=R. W. Alder |author2=M. E. Blake |author3=C. Bortolotti |author4=S. Buffali |author5=C. P. Butts |author6=E. Lineham |author7=J. M. Oliva |author8=A. G. Orpen |author9=M. J. Quayle |year=1999 |title=Complexation of stable carbenes with alkali metals |journal=Chem. Commun. |issue=3 |pages=241–242 |doi=10.1039/a808951e}}</ref> and acylic:<ref name="Alder1" /><ref name="Alder2" /><ref name="Alder3" /> {{vanchor|2NSatCNMRTables|text=center|thumb|600px|Some saturated metastable diaminocarbenes}} The most useful such carbenes are aromatic, for otherwise the Wanzlick equilibrium favors dimerization.<ref name="Denk1" /><ref name="Alder2" /> Typically, they are derived from imidazole or triazole rings. However, one stable ''N''-heterocyclic carbene derives from borazine:<ref name="Prasang-2005">{{cite journal |last1=Präsang |first1=C |last2=Donnadieu |first2=B |last3=Bertrand |first3=G |year=2005 |title=Stable Planar Six-π-Electron Six-Membered ''N''-Heterocyclic Carbenes with Tunable Electronic Properties |journal=J. Am. Chem. Soc. |volume=127 |issue=29 |pages=10182–10183 |doi=10.1021/ja052987g |pmc=2440681 |pmid=16028925|bibcode=2005JAChS.12710182P }}</ref>center|800px|frameless

==== Imidazol-2-ylidenes ==== Imidazol-2-ylidenes are known with alkyl, aryl,<ref name="Arduengo2">{{cite journal|author1=A. J. Arduengo |author2=H. V. R. Dias |author3=R. L. Harlow |author4=M. Kline |title = Electronic stabilization of nucleophilic carbenes|journal=J. Am. Chem. Soc.|year = 1992|volume = 114|pages = 5530–5534|doi = 10.1021/ja00040a007|issue = 14|bibcode=1992JAChS.114.5530A }}</ref> alkyloxy, alkylamino, alkylphosphino and even chiral substituents on the nitrogen atoms.<ref name="Herman1">{{cite journal |author1=W. A. Herrmann |author2=C. Kocher |author3=L. J. Goossen |author4=G. R. J. Artus |year=1996 |title=Heterocyclic Carbenes: A High-Yielding Synthesis of Novel, Functionalized ''N''-Heterocyclic Carbenes in Liquid Ammonia |journal=Chem. Eur. J. |volume=2 |issue=12 |pages=1627–1636 |doi=10.1002/chem.19960021222}}</ref>

1,3-Dimesityl-4,5-dichloroimidazol-2-ylidene, the first air-stable carbene, bears two chlorine atoms on the "backbone" ([http://ajarduengo.net/Jmol/htmlfiles/0173Viewer.html 3D]):<ref name="Arduengo5">{{cite journal|author1=A. J. Arduengo |author2=F. Davidson |author3=H. V. R. Dias |author4=J. R. Goerlich |author5=D. Khasnis |author6=W. J. Marshall |author7=T. K. Prakasha |title = An Air Stable Carbene and Mixed Carbene "Dimers"|journal=J. Am. Chem. Soc.|year = 1997|issue = 52|pages = 12742–12749|doi = 10.1021/ja973241o|volume = 119|bibcode=1997JAChS.11912742A }} </ref>

upright=0.7|alt=1,3-Dimesityl-4,5-dichloroimidazol-2-ylidene|center|frameless The chlorines likely reduce the electron density on the carbenic/ylidic carbon via induction through the σ system.

Because imidazolylidenes are stable against dimerization, molecules can contain multiple imidazol-2-ylidene groups:<ref name="Herman2">{{cite journal|author1=W. A. Herrmann |author2=M. Elison |author3=J. Fischer |author4=C. Kocher |author5=G. R. J. Artus |journal =Chem. Eur. J. |year = 1996|volume = 2|pages = 772–780|doi = 10.1002/chem.19960020708|title = ''N''-Heterocyclic Carbenes: Generation under Mild Conditions and Formation of Group 8–10 Transition Metal Complexes Relevant to Catalysis|issue = 7 |bibcode=1996ChEuJ...2..772H }}</ref><ref name="Dias1">{{cite journal|author1=H. V. R. Dias |author2=W. C. Jin |journal = Tetrahedron Lett.|year = 1994|volume = 35|pages = 1365–1366|doi = 10.1016/S0040-4039(00)76219-8|title = A stable tridentate carbene ligand|issue = 9}}</ref> <gallery mode="packed"> File:Poly-imidazolylidenes1.png File:Poly-imidazolylidenes2.png </gallery>

==== Triazol-5-ylidenes ==== In principle, triazol-5-ylidenes occur in two isomeric families, the 1,2,3-triazol-5-ylidenes and 1,2,4-triazol-5-ylidenes:

400px|center|Triazol-5-ylidene isomers.|frameless

Few such carbenes have been reported, but a triphenyl molecule is commercially available:{{Cn|date=June 2025}} alt=1,3,4-triphenyl-1,2,4-triazol-5-ylidene.|center|frameless|250x250px|Commercial 1,2,4-triazol-5-ylidene.

===Monoaminocarbenes=== The non-nitrogen atom adjacent to the carbene may be carbon (the cyclic monoamino carbenes),{{Cn|date=June 2025}} oxygen,<ref name="Alder4" /> sulfur,<ref name="Arduengo4" /><ref name="Alder4" /> or phosphorus:<ref name="Bertrand4" /><ref name="Bertrand5" />

center|thumb|upright=2.5|Synthesised heteroamino carbenes (top and bottom right) and Bertrand's carbenes (bottom left)

Since oxygen and sulfur are divalent, steric protection of the carbenic centre is particularly limited.

A claimed isothiazole carbene ('''2b''')<ref name="wolf2007">{{cite journal |last1=Wolf |first1=J |last2=Böhlmann |first2=W |last3=Findeisen |first3=M |last4=Gelbrich |first4=T |last5=Hofmann |first5=HJ |last6=Schulze |first6=B |year=2007 |title=Synthesis of stable isothiazole carbenes |journal=Angew. Chem. Int. Ed. |volume=46 |issue=17 |pages=3118–3121 |doi=10.1002/anie.200604305 |pmid=17372997 |bibcode=2007ACIE...46.3118W }}</ref> is not stable, rearranging instead to a β{{Nbh}}thiolactam:<ref name="DeHope-2006">{{cite journal |last1=DeHope |first1=A |last2=Lavallo |first2=V |last3=Donnadieu |first3=B |last4=Schoeller |first4=WW |last5=Bertrand |first5=G |year=2007 |title=Recently reported crystalline isothiazole carbenes: Myth or reality |journal=Angew. Chem. Int. Ed. |volume=46 |issue=36 |pages=6922–6925 |doi=10.1002/anie.200702272 |pmid=17661300 |bibcode=2007ACIE...46.6922D }}</ref><ref>{{cite journal |author1=Wolf Janine |author2=Böhlmann Winfried |author3=Findeisen Matthias |author4=Gelbrich Thomas |author5=Hofmann Hans-Jorg |author6=Schulze Borbel |year=2007 |title=Reply to "Recently Reported Crystalline Isothiazole Carbenes: Myth or Reality" |journal=Angew. Chem. Int. Ed. |volume=46 |issue=36 |page=6926 |doi=10.1002/anie.200702746 |bibcode=2007ACIE...46.6926W }}</ref>

frameless|upright=2.5|center

===Cyclopropenylidenes=== Another family of carbenes is based on a cyclopropenylidene core, a three-carbon ring with a double bond between the two atoms adjacent to the carbenic one. This family is exemplified by bis(diisopropylamino)cyclopropenylidene.<ref name="bertrand2006" />

===Bertrand's carbenes=== In Bertrand's persistent carbenes, the unsaturated carbon is bonded to a phosphorus and a silicon.<ref>{{cite journal|author1=G. Bertrand |author2=A. Igau |author3=A. Baceiredo |author4=G. Trinquier |journal =Angew. Chem. Int. Ed.|year = 1989|volume = 28|pages = 621–622|doi = 10.1002/anie.198906211|title = [Bis(diisopropylamino)phosphino]trimethylsilylcarbene: A Stable Nucleophilic Carbene|issue=5}} </ref> However, these compounds exhibit some alkynic properties and may instead be a hypervalent phosphaalkyne. The exact nature of these red oils remained unclear {{As of|2006|lc=y}}.<ref name="Bertrand5" /> center|thumb|600px|Alkyne and carbene resonances structures of Bertrand's carbene

===Triplet state carbenes=== Persistent carbenes tend to exist in the singlet, dimerizing when forced into triplet states. Nevertheless, Hideo Tomioka and associates used electron delocalization to produce a comparatively stable triplet carbene (bis(9-anthryl)carbene) in 2001. It has an unusually long half-life of 19 minutes.<ref>{{cite journal |last1=Tomioka |first1=H |last2=Iwamoto |first2=E |last3=Itakura |first3=H |last4=Hirai |first4=K |year=2001 |title=Generation and characterization of a fairly stable triplet carbene |journal=Nature |volume=412 |issue=6847 |pages=626–628 |bibcode=2001Natur.412..626T |doi=10.1038/35088038 |pmid=11493917 |s2cid=4373216 |ref={{harvid|Tomioka|2001}}}}</ref><ref>{{cite journal|journal = Chemical & Engineering News|date = 2001-08-13|volume = 79|issue = 33|pages = 11|url=http://pubs.acs.org/cen/topstory/7933/7933notw5.html|title = Triplet Carbene has Long Life|author1=Michael Freemantle|doi=10.1021/cen-v079n033.p011a|url-access = subscription}}</ref> Metal (Pb, Pd, Pt) substituted triplet carbenes (metalla-carbenes) are only stable in the cold.[10][11]

[[File:Tomioka Carbene 2001.svg|center|thumb|650px|Delocalization in a stable triplet carbene reported by {{Harvtxt|Tomioka|2001}}. Note that the molecule is not planar; each arene system forms a plane perpendicular to the other]]

In 2006 a triplet carbene was reported by the same group with a half-life of 40 minutes. This carbene is prepared by a photochemical decomposition of a diazomethane precursor by 300&nbsp;nm light in benzene with expulsion of nitrogen gas.<ref>{{cite journal |last1=Itoh |first1=T |last2=Nakata |first2=Y |last3=Hirai |first3=K |last4=Tomioka |first4=H |year=2006 |title=Triplet Diphenylcarbenes Protected by Trifluoromethyl and Bromine Groups. A Triplet Carbene Surviving a Day in Solution at Room Temperature |journal=J. Am. Chem. Soc. |volume=128 |issue=3 |pages=957–967 |doi=10.1021/ja056575j |pmid=16417387 |bibcode=2006JAChS.128..957I |ref={{harvid|Itoh|2006}}}}</ref>

[[File:Persistent triplet carbene.png|center|thumb|600px|A persistent triplet carbene (right), synthesized by {{Harvtxt|Itoh|2006}}. Note that the molecule is neither bent at the central carbon nor planar; that carbon is ''sp'' hybridized and each arene system forms a plane perpendicular to the other]]

Exposure to oxygen (a triplet diradical) converts this carbene to the corresponding benzophenone. A diphenylmethane compound{{Which|date=June 2025}} is formed when it is trapped by cyclohexa-1,4-diene.{{Cn|date=June 2025}}

As with the other carbenes, this species contains large bulky substituents, namely bromine and the trifluoromethyl groups on the phenyl rings, that shield the carbene and prevent or slow down the process of dimerization to a 1,1,2,2-tetra(phenyl)alkene. Based on computer simulations, the distance of the divalent carbon atom to its neighbors is claimed to be 138 picometers with a bond angle of 158.8°. The planes of the phenyl groups are almost at right angles to each other (the dihedral angle being 85.7°).{{OR?|date=June 2025}}

=== Mesoionic carbenes === Mesoionic carbenes (MICs) are similar to ''N''-heterocyclic carbenes (NHCs), except that canonical resonance structures with the carbene depicted cannot be drawn without adding additional charges. Mesoionic carbenes are also referred to as abnormal ''N''-heterocyclic carbenes (aNHC) or remote ''N''-heterocyclic carbenes (rNHC).

==Chemical properties== Enders ''et al.''<ref name="Enders-1995">{{cite journal |author1=D. Enders |author2=K. Breuer |author3=G. Raabe |author4=J. Runsink |author5=J. H. Teles |author6=J. P. Melder |author7=K. Ebel |author8=S. Brode |year=1995 |title=Preparation, Structure, and Reactivity of 1,3,4-Triphenyl-4,5-dihydro-1''H''-1,2,4-triazol-5-ylidene, a New Stable Carbene |journal=Angew. Chem. Int. Ed. |volume=34 |issue=9 |pages=1021–1023 |doi=10.1002/anie.199510211}}</ref><ref name="Enders-2019">{{cite journal |author1=Enders, D. |author2=Breuer, K. |author3=Runsink, J. |author4=Teles, J.H. |year=1996 |journal=Liebigs Ann. Chem. |pages=2019–2028|title=Chemical Reactions of the Stable Carbene 1,3,4-Triphenyl-4,5-dihydro-1''H''-1,2,4-triazol-5-ylidene|volume=1996 |issue=12 |doi=10.1002/jlac.199619961212}}</ref><ref name=Enders-1997> {{cite journal |author1=Enders, D. |author2=Breuer, K. |author3=Teles, J.H. |author4=Ebel, K. |year=1997 |journal=J. Prakt. Chem. |pages=397–399 |title=1,3,4-Triphenyl-4,5-dihydro-1''H''-1,2,4-triazol-5-ylidene – applications of a stable carbene in synthesis and catalysis |doi=10.1002/prac.19973390170 |volume=339}}</ref> have performed a range of organic reactions involving a model triazol-5-ylidene: [[File:triazol5ylidene reactions.png|center|thumb|600px| {|class=wikitable |+Reactions of triazol-5-ylidene<ref name=Enders-1997/> !a |3,6-diphenyl-1,2,4,5-tetrazine, toluene |92% |style="border-top: 0px; border-bottom: 0px"| !e |2 equiv., PhNCO, toluene, reflux |92% |- !b |RXH, RT |95–97% |style="border-top: 0px; border-bottom: 0px"| !f |CS₂, toluene, or PhNCS, THF, RT |71–90% |- !c |O₂, S₈, or Se, toluene, reflux |54–68% |style="border-top: 0px; border-bottom: 0px"| !g |Maleimide, THF, RT |47–84% |- !d |R₁CH=CHR², THF, RT |25–68% |style="border-top: 0px; border-bottom: 0px"| !h |Dimethylacetylene dicarboxylate, THF, reflux |21% |}]] The unprotonated molecule performed nucleophilic addition ('''e''' and '''f'''), possibly in conjugate ('''d''', '''g''' and '''h'''). As a base, it abstracts labile protons easily; the resulting cation can easily add a nucleophile (a net insertion reaction; '''b'''). Chalcogens add at the carbene to recover the (thio)urea ('''c''') and activated dienes add the carbene in [4+1] cycloadditions ('''a''').

===Basicity and nucleophilicity===

The imidazol-2-ylidenes are strong bases, having conjugate p''K''_a&nbsp;≈&nbsp;24 in dimethyl sulfoxide (DMSO):<ref name=Alder6/>

center|600px|Measurement of the pKa value for the conjugate acid of an imidazol-2-ylidene|frameless

Conjugate p''K''_a values for several NHC families have been examined in aqueous solution. pK_a values of triazolium ions lie in the range 16.5–17.8,<ref>{{cite journal |author=Massey Richard S |year=2012 |title=Proton Transfer Reactions of Triazol-3-ylidenes: Kinetic Acidities and Carbon Acid pKaValues for Twenty Triazolium Salts in Aqueous Solution |url=http://dro.dur.ac.uk/17557/1/17557.pdf |journal=J. Am. Chem. Soc. |volume=134 |issue=50 |pages=20421–20432 |doi=10.1021/ja308420c |pmid=23173841|bibcode=2012JAChS.13420421M }}</ref> around 3 p''K''_a units more acidic than related imidazolium ions.<ref>{{Cite journal |last1=Higgins |first1=Eleanor M. |last2=Sherwood |first2=Jennifer A. |last3=Lindsay |first3=Anita G. |last4=Armstrong |first4=James |last5=Massey |first5=Richard S. |last6=Alder |first6=Roger W. |last7=O'Donoghue |first7=Annmarie C. |year=2011 |title=p''K''_as of the conjugate acids of ''N''-heterocyclic carbenes in water |url=https://semanticscholar.org/paper/666ab73922ee8874fa58dfa9f87544420f4f40bb |journal=Chem. Commun. |volume=47 |issue=5 |pages=1559–1561 |doi=10.1039/C0CC03367G |pmid=21116519 |s2cid=205757477}}</ref> Contrariwise, diaminocarbenes will deprotonate DMSO solvent, with the resulting anion reacting with the resulting amidinium salt:

[[File:AlderTIPcarbeneDMSO.png|center|thumb|600px|Using D6-DMSO as an NMR solvent can have unexpected results.]]

The molecules are likely also reasonably nucleophilic. Reaction of imidazol-2-ylidenes with 1-bromohexane gave 90% of the 2-substituted adduct, with only 10% of the corresponding alkene.

Stable carbenes derived from thiazole underlie the action of thiamine in biological systems, and its biomimetic descendant, the Stetter reaction.<ref>{{cite journal |author=R. Breslow |year=1957 |title=Rapid Deuterium Exchange in Thiazolium Salts |journal=J. Am. Chem. Soc. |volume=79 |issue=7 |pages=1762–1763 |doi=10.1021/ja01564a064|bibcode=1957JAChS..79.1762B }}</ref>

===Dimerisation=== At one time, stable carbenes were thought to reversibly dimerise through the so-called Wanzlick equilibrium.<ref name="AlderEtDAC" /> The uncatalyzed reaction is typically slow,<ref>{{cite journal |last1=Messelberger |first1=J. |last2=Kumar |first2=M. |last3=Goodner |first3=S. J. |last4=Munz |first4=D. |title=Wanzlick's Equilibrium in Tri- and Tetraaminoolefins |journal=Organic Chemistry Frontiers |year=2021 |volume=8 |page=6663 |doi=10.1039/D1QO01320C|doi-access=free }}</ref> presumably in part because direct, planar dimerization ('''A''') requires first crossing the high singlet-triplet barrier. In the preferred pathway ('''B'''), the empty carbon ''p'' orbital attacks a nearby carbene lone pair:<ref name="Alderreview">{{cite journal |last1=Alder |first1=Roger W. |last2=Blake |first2=Michael E. |last3=Chaker |first3=Leila |last4=Harvey |first4=Jeremy N. |last5=Paolini |first5=François |last6=Schütz |first6=Jan |year=2004 |title=When and How Do Diaminocarbenes Dimerize? |journal=Angew. Chem. Int. Ed. |volume=43 |issue=44 |pages=5896–5911 |doi=10.1002/anie.200400654 |pmid=15457494 |bibcode=2004ACIE...43.5896A |doi-access=free}}</ref>

center|600px|frameless Protons, which create formamidinium salts, catalyze the reaction,<ref name="AlderEtDAC" /> as do other Lewis acids.<ref name="Alderreview" />

However, imidazol-2-ylidenes and triazol-5-ylidenes are thermodynamically stable and do not dimerise even under relatively forcing conditions. They have been stored in solution in the absence of water and air for years. This is presumably due to the aromatic nature of these carbenes, which is lost upon dimerisation.<ref name="Denk1" /><ref name="Alder2" />

Chen and Taton demonstrated that a sufficiently short tether (i.e., propylene, but not butylene) could force aromatic stable carbenes to dimerize:<ref name="Chen">{{cite journal |author1=T. A. Taton |author2=P. Chen |year=1996 |title=A Stable Tetraazafulvalene |journal=Angew. Chem. Int. Ed. |volume=35 |issue=9 |pages=1011–1013 |doi=10.1002/anie.199610111}}</ref>

center|300px|Dimerisation of tethered diimidazol-2-ylidenes|frameless

If a dicarbene, the carbenic lone pairs would be forced into close proximity. To avoid electrostatic repulsion between the lone pairs, the orbitals hybridize into bonds.

===Metal complexes=== {{Main|Transition metal NHC complex}} Imidazol-2-ylidenes, triazol-5-ylidenes (and less so, diaminocarbenes) coordinate to a plethora of elements: from main group elements, transition metals and actinides to even alkali metals and lanthanides. A periodic table of elements gives some idea of the complexes which have been prepared. {{Periodic table (persistent carbene)}} In many cases, the complexes have been identified by single crystal X-ray crystallography.<ref name="Alder5" /><ref name="Herrmann3">{{cite journal|title = ''N''-Heterocyclic Carbenes|journal =Angew. Chem. Int. Ed.|volume = 36|issue = 20|year = 1997|pages = 2162–2187|author1=Wolfgang A. Herrmann |author2=Christian Köcher |doi = 10.1002/anie.199721621|s2cid =97336589}}</ref><ref name="Boche1">{{cite journal|title = Crystal Structure of the Dimeric (4-''tert''-Butylthiazolato)(glyme)lithium: Carbene Character of a Formyl Anion Equivalent|journal =Angew. Chem. Int. Ed.|volume = 34|issue = 4|year = 1995|pages = 487–489|author1=Gernot Boche |author2=Christof Hilf |author3=Klaus Harms |author4=Michael Marsch |author5=John C. W. Lohrenz |doi =10.1002/anie.199504871}}</ref> Stable carbenes are roughly isolobal with organophosphines. The carbenic lone pair is a good σ donor, and the adjacent, stabilizing heteroatoms enrich the π system with such electrons as to inhibit π backbonding. Enders<ref name="Enders-ChemBer-1996">{{cite journal|author1=D. Enders |author2=H. Gielen |author3=G. Raabe |author4=J. Runsink |author5=J. H. Teles |journal = Chem. Ber.|year = 1996|volume = 129|pages = 1483–1488|doi = 10.1002/cber.19961291213|title = Synthesis and Stereochemistry of the First Chiral (Imidazolinylidene)- and (Triazolinylidene)palladium(II) Complexes|issue = 12}} </ref> and Hermann<ref name="Herrmann3" /><ref name="Herrman4"> {{cite journal|title = Metal Complexes of ''N''-Heterocyclic Carbenes – A New Structural Principle for Catalysts in Homogeneous Catalysis|journal =Angew. Chem. Int. Ed.|issue = 21|year = 1995|pages = 2371–2374|author1=Wolfgang A. Herrmann |author2=Martina Elison |author3=Jakob Fischer |author4=Christian Köcher |author5=Georg R. J. Artus |doi = 10.1002/anie.199523711|volume = 34}} </ref><ref name="Herrman5"> {{cite journal|title = Chiral Heterocylic Carbenes in Asymmetric Homogeneous Catalysis|journal =Angew. Chem. Int. Ed.|volume = 35|issue = 23–24|year = 1996|pages = 2805–2807|author1=Wolfgang A. Herrmann |author2=Lukas J. Goossen |author3=Christian Köcher |author4=Georg R. J. Artus |doi = 10.1002/anie.199628051}} </ref> have shown ligand rough equivalence between stable carbenes and organophosphines in several catalytic cycles: the carbenes do not activate the metal near so much, but the resulting complexes are far more robust. Grubbs has reported replacing a phosphine ligand (PCy₃) with an imidazol-2-ylidene in the olefin metathesis catalyst RuCl₂(PCy₃)₂CHPh, and noted increased ring closing metathesis as well as exhibiting "a remarkable air and water stability".<ref name="Grubbs1"> {{cite journal|author1=M. Scholl |author2=T. M. Trnka |author3=J. P. Morgan |author4=R. H. Grubbs |journal = Tetrahedron Lett.|year = 1999|volume = 40|pages = 2247–2250|doi = 10.1016/S0040-4039(99)00217-8|title = Increased ring closing metathesis activity of ruthenium-based olefin metathesis catalysts coordinated with imidazolin-2-ylidene ligands|issue = 12}} </ref>

Molecules containing two and three carbene moieties have been prepared as potential bidentate and tridentate carbene ligands.<ref name="Herman2" /><ref name="Dias1" />

==Physical properties==

Those carbenes that have been isolated to date tend to be colorless solids with low melting points. These carbenes tend to sublime at low temperatures under high vacuum.{{Cn|date=June 2025}}

X-ray structures of imidazolic carbenes show N–C–N bond angles of 103–110°, but typically 104°.<ref name="HZGBS">{{cite journal |display-authors=3 |vauthors=Haque RA, Zulikha HZ, Ghdhayeb MZ, Budagumpi S, Salman AW |date=January 2012 |title=Cationic Nitrile-Functionalized Ag(I)- and Hg(II)-N-Heterocyclic Carbene Complexes of CCC, CNC, and NCN Pincer-Type Carbene Ligands: Synthesis, Crystal Structures, and Characterization |journal=Heteroatom Chemistry |publisher=Wiley |volume=23 |issue=5 |pages=486–497 |doi=10.1002/hc.21041 |doi-access=free}}</ref><ref name="HCBAAM">{{cite journal |display-authors=3 |vauthors=Haque RA, Choo SY, Budagumpi S, Abdullah AA, Ahamed MK, Majid AA |date=July 2015 |title=Synthesis, crystal structures, characterization and biological studies of nitrile-functionalized silver(I) N-heterocyclic carbene complexes |journal=Inorganica Chimica Acta |volume=433 |pages=35–44 |doi=10.1016/j.ica.2015.04.023 |doi-access=free}}</ref><ref name=HGBSAM>{{cite journal |display-authors=3 |vauthors=Haque RA, Ghdhayeb MZ, Budagumpi S, Salman AW, Ahamed MK, Majid AA |date=January 2013 |title=Non-symmetrically substituted N-heterocyclic carbene–Ag(I) complexes of benzimidazol-2-ylidenes: Synthesis, crystal structures, anticancer activity and transmetallation studies |journal=Inorganica Chimica Acta |volume=394 |pages=519–525 |doi=10.1016/j.ica.2012.09.013 |doi-access=free}}</ref><ref name="LZWGW">{{cite journal |display-authors=3 |vauthors=Liu QX, Zhao XJ, Wu XM, Guo JH, Wang XG |date=December 2007 |title=New mercury(II) and silver(I) complexes containing NHC metallacrown ethers with the π–π stacking interactions |journal=Journal of Organometallic Chemistry |publisher=Elsevier |volume=692 |issue=25 |pages=5671–5679 |doi=10.1016/j.jorganchem.2007.09.027 |doi-access=free}}</ref> Nonaromatic carbenes typically exhibit larger angles: dihydroimidazole-2-ylidene shows a N–C–N bond angle of about 106°, whilst the angle of an acyclic carbene{{Which|date=June 2025}} is 121°. Contrariwise, monoamino carbenes X-ray structures have shown N–C–X bond angles of around 104° and 109° respectively.{{Cn|date=June 2025}}

===NMR=== One of the more useful physical properties is the diagnostic chemical shift of the carbenic carbon atom in the ¹³C-NMR spectrum. Typically this peak is in the range between 200 and 300 ppm, where few other peaks appear in the ¹³C-NMR spectrum. For example, bis(isopropyl)imidazolidinylidene exhibits a peak at 238&nbsp;ppm:{{Cn|date=June 2025}} Carbene peak in ¹³C NMR|center|frameless|upright=4 Imidazole-based carbenes generally have diagnostic ¹³C&nbsp;NMR chemical shift values between 210 and 230&nbsp;ppm for the carbenic carbon:<ref>{{cite journal |last1=Tapu |first1=Daniela |last2=Dixon |first2=David A. |last3=Roe |first3=Christopher |date=12 August 2009 |title=13C NMR Spectroscopy of "Arduengo-type" Carbenes and Their Derivatives |journal=Chem. Rev. |volume=109 |issue=8 |pages=3385–3407 |doi=10.1021/cr800521g |pmid=19281270}}</ref> center|frameless|Stable imidazol-2-ylidenes|upright=1.3 Triazole-based carbenes have shifts between 210 and 220&nbsp;ppm, while nonaromatic diaminocarbenes have shifts between 230 and 270&nbsp;ppm (see diagram). Acyclic, monoamino carbenes have shifts between 250 and 300&nbsp;ppm for the carbenic carbon, further downfield than any other table carbene.{{cn|date=February 2024}}

Upon coordination to metal centers, the ¹³C carbene resonance usually shifts highfield, depending on the Lewis acidity of the complex fragment. Based on this observation, Huynh ''et al.'' developed a new methodology to determine ligand donor strengths by ¹³C NMR analysis of ''trans''-palladium(II)-carbene complexes. The use of a ¹³C-labeled N-heterocyclic carbene ligand also allows for the study of mixed carbene-phosphine complexes, which undergo ''trans''-''cis''-isomerization due to the trans effect.<ref> {{cite journal|doi = 10.1021/om900667d|journal = Organometallics|title = 13C NMR Spectroscopic Determination of Ligand Donor Strengths Using N-Heterocyclic Carbene Complexes of Palladium(II)|year = 2009|author = Han Vinh Huynh | volume = 28|issue = 18|pages = 5395–5404 |display-authors = 1 |last2 = Han |first2 = Yuan |last3 = Jothibasu |first3 = Ramasamy |last4 = Yang |first4 = Jie An|doi-access = free }} </ref>

==Aspirational applications== right|thumb|150px|A second generation Grubbs' catalyst. In academia, NHCs are widely-used ancillary ligands. They are components of the ruthenium-based Grubbs' catalyst for olefin metathesis, which have been intensively investigated. NHC-Palladium Complexes catalyze cross-coupling reactions.<ref>S. P. Nolan [editor] (2006). [https://books.google.com/books?id=9JOG1g9iFrwC N-Heterocyclic carbenes in synthesis], Wiley-VCH {{ISBN|3-527-31400-8}}</ref><ref>F. Glorius [editor] (2007) [https://books.google.com/books?id=Fv2orfXKVnoC&pg=PP1 N-Heterocyclic carbenes in transition metal catalysis], Springer {{ISBN|3-540-36929-5}} </ref><ref>{{Cite journal|last1= Díez-González|first1=Silvia|last2=Marion|first2=Nicolas|last3=Nolan|first3=Steven P.|date=2009-08-12|title=N-Heterocyclic Carbenes in Late Transition Metal Catalysis|journal=Chem. Rev.|volume=109|issue=8|pages=3612–3676|doi=10.1021/cr900074m|pmid=19588961|s2cid=206902952|issn=0009-2665}}</ref>

Ag(I)-NHC complexes have been widely tested for their biological applications.<ref>{{cite journal |author1=Garrison Jered C. |author2=Youngs Wiley J. | year = 2005 | title = Ag(I) N-Heterocyclic Carbene Complexes: Synthesis, Structure, and Application | journal = Chem. Rev. | volume = 105 | issue = 11| pages = 3978–4008 | doi = 10.1021/cr050004s |pmid=16277368 |s2cid=43090499 }}</ref>

==Preparation methods== NHCs are often strongly basic (the pKa value of the conjugate acid of an imidazol-2-ylidene was measured at ca. 24)<ref name=Alder6> {{cite journal|author1=R. W. Alder |author2=P. R. Allen |author3=S. J. Williams |journal=Chem. Commun.|year = 1995|pages = 1267|doi = 10.1039/c39950001267|title = Stable carbenes as strong bases|issue = 12}} </ref> and react with oxygen. Their synthesis, then must be performed free of air and compounds of even moderate acidity. Conversely, provided rigorously dry, relatively non-acidic and air-free materials are used, stable carbenes are reasonably robust to handling ''per se''. [[File:Kcarbene.png|thumb|right|300px|X-ray structure of a KHMDS-diaminocarbene complex, formed when excess KHMDS was used to deprotonate the parent formamidinium salt.{{Cn|date=June 2025}} ]] The simplest syntheses deprotonate a parent salt, but the byproducts can be difficult to separate out, because NHCs coordinate strongly to even alkali metal cations. Potassium and sodium salts tend to precipitate from solution and can be removed, but lithium ions are especially problematic, requiring cryptands or crown ethers.

Alternate techniques have been developed to avoid such purification difficulties.

===Deprotonation=== Deprotonation of carbene precursor salts with strong bases reliably produces almost all stable carbenes:

center|thumb|600px|Deprotonation of precursor salts to give stable carbenes.

Imidazol-2-ylidenes and dihydroimidazol-2-ylidenes, such as IMes, have been prepared by the deprotonation of the respective imidazolium and imidazolinium salts. Acyclic carbenes<ref name=Alder1/><ref name=Alder2/> and tetrahydropyrimidinyl-based carbenes<ref name=Alder5/> were prepared by deprotonation using strong homogeneous bases.

However, the reaction depends on the correct choice of base. Although imidazolium salt precursors are stable to nucleophilic addition, other non-aromatic salts (i.e. formamidinium salts) are not.<ref name="Alderformamidinium">{{cite journal |author1=Roger W. Alder |author2=Michael E. Blake |author3=Simone Bufali |author4=Craig P. Butts |author5=A. Guy Orpen |author6=Jan Schütz |author7=Stuart J. Williams |year=2001 |title=Preparation of tetraalkylformamidinium salts and related species as precursors to stable carbenes |journal=J. Chem. Soc., Perkin Trans. 1 |issue=14 |pages=1586–1593 |doi=10.1039/b104110j}} </ref> In these cases, strong unhindered nucleophiles are avoided whether they are generated in ''situ'' or are present as an impurity in other reagents (such as LiOH in BuLi).

Alkyllithiums are unreliable bases for the reaction,<ref name="Arduengo1" /> because they are too nucleophilic and often act as hydridic reductants:

[[File:Basebutyllithium.png|center|600px|Reduction of formamidinium salts with tert-butyllithium|frameless]]

In principle, sodium or potassium hydride<ref name="Arduengo3" /><ref name="Arduengo4" /> would be the ideal base for deprotonating these precursor salts, but in practice the salt dissolves too slowly for effective reaction. DMSO or ''t''-BuOH catalyze the reaction through the soluble tert-butoxide or dimsyl anion bases,<ref name="Arduengo1" /><ref name="Arduengo2" /> but those compounds are too nucleophilic for non-aromatic carbenes. Deprotonation with sodium or potassium hydride in a mixture of liquid ammonia/THF at −40&nbsp;°C has been reported<ref name="Herman1" /> for imidazole-based carbenes, and Arduengo and coworkers<ref name="Arduengo4" /> managed to prepare a dihydroimidazol-2-ylidene using NaH. However, this method has not been applied to the preparation of diaminocarbenes.

In some cases, potassium tert-butoxide can be employed directly.<ref name="Arduengo2" />

Lithium amides like the diisopropylamide (LDA) and tetramethylpiperidide (LiTMP)<ref name="Alder1" /><ref name="Alder2" /> generally work well for the deprotonation of all types of salts, providing that not too much LiOH impurity is present. Metal hexamethyldisilazides<ref name="Alder5" /> deprotonate almost all salts cleanly, except for unhindered formamidinium salts, where this base can act as a nucleophile to give a triaminomethane adduct.

=== Dechalcogenation and dechlorination === For carbenes stable at elevated temperatures, a rare approach desulfurizes thioureas in THF with molten potassium:<ref name="Denk1" /><ref>{{cite journal|author1=N. Kuhn |author2=T. Kratz |journal = Synthesis|year = 1993|pages = 561–562|doi = 10.1055/s-1993-25902|title = Synthesis of Imidazol-2-ylidenes by Reduction of Imidazole-2(3''H'')-thiones|volume = 1993|issue = 6}}</ref> center|frameless|500x500px A contributing factor to the reaction's success is that the potassium sulfide byproduct is insoluble in the solvent.{{Cn|date=June 2025}}

A single example of deoxygenating a urea with a fluorene derived carbene to give the tetramethyldiaminocarbene and fluorenone has also been reported:<ref>{{cite journal|title = Carbene-to-Carbene Oxygen Atom Transfer|author1=D. Kovacs |author2=M. S. Lee |author3=D. Olson |author4=J. E. Jackson |journal = J. Am. Chem. Soc.|year = 1996|volume = 118|pages = 8144–8145|doi = 10.1021/ja961324j|issue = 34|bibcode=1996JAChS.118.8144K }}</ref> center|frameless|500x500px Bis(trimethylsilyl)mercury (CH₃)₃Si-Hg-Si(CH₃)₃ reacts with chloro-iminium and chloro-amidinium salts to give a metal-free carbene and elemental mercury.<ref>{{cite journal |author1=Michael Otto |author2=Salvador Conejero |author3=Yves Canac |author4=Vadim D. Romanenko |author5=Valentyn Rudzevitch |author6=Guy Bertrand |year=2004 |title=Mono- and Diaminocarbenes from Chloroiminium and -amidinium Salts: Synthesis of Metal-Free Bis(dimethylamino)carbene |journal=J. Am. Chem. Soc. |volume=126 |issue=4 |pages=1016–1017 |doi=10.1021/ja0393325 |pmid=14746458|bibcode=2004JAChS.126.1016O }}</ref> For example: :(CH₃)₃Si−Hg−Si(CH₃)₃ + R₂N=C(Cl)−{{chem|NR|2|+}}Cl⁻ → R₂N−C−NR₂ + Hg_{{{abbr|(l)|liquid}}} + 2(CH₃)₃SiCl

=== Vacuum pyrolysis === Vacuum pyrolysis, with the removal of neutral volatile byproducts i.e. methanol or chloroform, has been used to prepare dihydroimidazole and triazole based carbenes. Historically the removal of chloroform by vacuum pyrolysis of adducts '''A''' was used by Wanzlick<ref name="Wanzlick2" /> in his early attempts to prepare dihydroimidazol-2-ylidenes but this method is not widely used. The Enders laboratory has used vacuum pyrolysis of adduct '''B''' to generate a triazol-5-ylidene:<ref name="Enders-1995" />

center|thumb|400px|Preparation of carbenes via vacuum pyrolysis.

===Purification=== A stable carbene prepared from potassium hydride can be filtered through a dry celite pad to remove excess KH (and resulting salts) from the reaction. On a relatively small scale, a suspension containing a stable carbene in solution can be allowed to settle and the supernatant solution pushed through a dried membrane syringe filter.

Recrystallisation of stable carbenes is difficult, because stable carbenes are readily soluble in non-polar solvents, and polar solvents are insuitably acidic.

Air-free sublimation purifies effectively, even giving monocrystals suitable for X-ray analysis. However, strong complexation to metal ions like lithium will in most cases prevent sublimation. Also, the process must be performed at high vacuum, as persistent carbenes decompose above 60&nbsp;°C. thumb|600x600px|Apparatus:<dl> <dt>a</dt><dd>Rubber cone (typically used to form a vacuum seal in a Büchner flask filtration) which is selected so as to fit snugly around the neck of the Schlenk tube</dd> <dt>b</dt><dd>Schlenk tube</dd> <dt>c</dt><dd>Gas/vacuum inlet</dd> <dt>d</dt><dd>Teflon tap (or stopcock)</dd> <dt>e</dt><dd>Syringe</dd> </dl> Method (steps '''4''' and '''5''' can be repeated as required; steps '''6''' and '''7''' are not essential):<dl> <dt>1</dt><dd>Impure solid to sublime (brown) is placed in a Schlenk tube, avoiding contaminating the sides of the tube (e.g. by careful evaporation from a solution containing the brown solid).</dd> <dt>2</dt><dd>Rubber cone (black) is pushed near top of the Schlenk tube (forming a tight seal around flask) and filled with a coolant such as dry ice/acetone (blue/white). The bottom of the Schlenk tube is heated (red shading) under vacuum (blue arrow), so that the impure solid (brown) sublimes as a pure solid (purple) at the cooled neck area (blue shading).</dd> <dt>3</dt><dd>The flask is held under an atmosphere of an inert gas via Schlenk tube side arm, until step '''7'''. The cooling-cone (black) is removed, leaving the concentrated impurity as a residue (dark brown) in the bottom of the flask, and the purified sublimed solid (purple) at the neck.</dd> <dt>4</dt><dd>Solvent (blue) is inserted via syringe to dissolve the residue (green/brown), taking care to avoid washing off the sublimed solid (purple).</dd> <dt>5</dt><dd>Residue solution is then removed by syringe (green/brown).</dd> <dt>6</dt><dd>Purified sublimed solid (purple) is washed off the neck of the flask with fresh solvent (blue) via a syringe.</dd> <dt>7</dt><dd>Solvent is removed under vacuum to give the purified sublimed solid (dark purple).</dd> </dl>|center

==References== {{Reflist|30em}}

==Further reading== Reviews on persistent carbenes: * {{cite journal|author1=Hopkinson, M. N. |author2=Richter, C. |author3=Schedler, M. |author4=Glorius, F. |title=An Overview of N-Heterocyclic Carbenes|journal=Nature|year=2014|volume=510|issue=7506 |pages=485–496|doi=10.1038/nature13384 |pmid=24965649|bibcode=2014Natur.510..485H|s2cid=672379 }}. * [https://books.google.com/books?id=ElV85eHbubQC&dq=Alder+Bertrand&pg=PA153 Carbene Chemistry: From Fleeting Intermediates to Powerful Reagents, (Chapter 4, Hideo Tomioka (triplet state); Chapter 5 (singlet state), Roger W. Alder) - ed. Guy Bertrand] * [https://books.google.com/books?id=wp0C10qO0A8C&dq=moss+jones+platz+Bertrand&pg=PA329 Reactive Intermediate Chemistry By Robert A. Moss, Matthew Platz, Maitland Jones (Chapter 8, Stable Singlet Carbenes, Guy Bertrand)] * R. W. Alder, in 'Diaminocarbenes: exploring structure and reactivity', ed. G. Bertrand, New York, 2002 * {{cite journal|author=M. Regitz|title=Stable Carbenes—Illusion or Reality?|journal=Angew. Chem. Int. Ed.|year=1996|volume=30|issue=6|pages=674–676|doi=10.1002/anie.199106741}}

For a review on the physico-chemical properties (electronics, sterics, ...) of N-heterocyclic carbenes: * {{cite journal |author1=T. Dröge |author2=F. Glorius |title=The Measure of All Rings - N-Heterocyclic Carbenes |journal=Angew. Chem. Int. Ed. |year=2010 |volume=49 |pages=6940–6952 |doi=10.1002/anie.201001865 |issue=39 |pmid=20715233 |bibcode=2010ACIE...49.6940D }}

Category:Functional groups Category:Carbenes Category:Organometallic chemistry Category:Organic compounds