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A persistent carbene (also known as stable carbene) is an organic molecule whose natural resonance structure has a carbon atom with octet rule (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) (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 Aromaticity 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 in organometallic chemistry.
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. Chemists Approach Elusive Breslow Intermediate Carmen Drahl
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. 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; and by Winberg in 1965. However, subsequent experiments by Denk, Herrmann and others have confirmed this equilibrium, albeit in specific circumstances.
In 1988, Guy Bertrand and others isolated a phosphinocarbene. These species can be represented as either a λ3-phosphinocarbene or λ5-phosphaacetylene:
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 alkyne 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 °C.
In 1991, Arduengo and coworkers obtained the first crystalline diaminocarbene by deprotonation of an imidazolium cation:
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 °C without decomposition.
The first air-stable Arduengo carbene, a chlorinated member of the imidazol-2-ylidene family, was obtained in 1997.
That persistent carbenes have ylidic character is hardly obvious, and indeed was initially contradicted. The X-ray structure of N, -diadamantyl-imidazol-2-ylidene revealed longer N–C in the ring of the carbene than in the parent imidazolium compound, suggesting very little double bond character to these bonds. Hence early workers attributed the stability of Arduengo carbenes to the bulky N-adamantyl substituents, which steric hindrance with other molecules.
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 ( 3D):
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. The following year, the first acyclic persistent carbene demonstrated that stability did not require even cyclicity.
Unhindered derivatives of the hydrogenated and acyclic 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.
Subsequent research has focused on expanding the array of Heteroatom stabilizing the ylide. Most persistent carbenes are stabilized by two flanking nitrogen centers. The outliers include an aminothiocarbene and an aminooxycarbene ( 3D)... ...and room-temperature-stable bis(diisopropylamino)cyclopropenylidene, in which the amines are connected through vinylogy. In 2000, Bertrand obtained a moderately stable (amino)(aryl)carbene with only one heteroatom adjacent to the carbenic atom.
Carbenes with sulfur, oxygen, or other at both Locant locations are expected to dissociate into an alkyne (R1C≡CR2) and a carbon chalcogenide (X1=C=X2). 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.
The most useful such carbenes are aromatic, for otherwise the Wanzlick equilibrium favors dimerization. Typically, they are derived from imidazole or triazole rings. However, one stable N-heterocyclic carbene derives from borazine:
1,3-Dimesityl-4,5-dichloroimidazol-2-ylidene, the first air-stable carbene, bears two chlorine atoms on the "backbone" ( 3D):
The chlorines likely reduce the electron density on the carbenic/ylidic carbon via inductive effect through the σ system.
Because imidazolylidenes are stable against dimerization, molecules can contain multiple imidazol-2-ylidene groups:
Few such carbenes have been reported, but a triphenyl molecule is commercially available:
Since oxygen and sulfur are divalent, steric protection of the carbenic centre is particularly limited.
A claimed isothiazole carbene ( 2b) is not stable, rearranging instead to a βthiolactam:
[[File:Tomioka Carbene 2001.svg|center|thumb|650px|Delocalization in a stable triplet carbene reported by . 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 photochemistry decomposition of a diazomethane precursor by 300 nanometer light in benzene with expulsion of nitrogen gas.
[[File:Persistent triplet carbene.png|center|thumb|600px|A persistent triplet carbene (right), synthesized by . 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 is formed when it is trapped by cyclohexa-1,4-diene.
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 bond length of the divalent carbon atom to its neighbors is claimed to be 138 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°).
| +Reactions of triazol-5-ylidene !a | 3,6-diphenyl-1,2,4,5-tetrazine, toluene | 92% | !e2 equiv., PhNCO, toluene, reflux | 92% |
Conjugate p Ka values for several NHC families have been examined in aqueous solution. pKa values of triazolium ions lie in the range 16.5–17.8, around 3 p Ka units more acidic than related imidazolium ions. Contrariwise, diaminocarbenes will deprotonate DMSO solvent, with the resulting anion reacting with the resulting amidinium salt:
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 Biomimetics descendant, the Stetter reaction.
Protons, which create formamidinium salts, catalyze the reaction, as do other Lewis acids.
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.
Chen and Taton demonstrated that a sufficiently short tether (i.e., propylene, but not butylene) could force aromatic stable carbenes to dimerize:
If a dicarbene, the carbenic would be forced into close proximity. To avoid electrostatic repulsion between the lone pairs, the orbitals hybridize into bonds.
In many cases, the complexes have been identified by single crystal X-ray crystallography.
Stable carbenes are roughly isolobal with . The carbenic lone pair is a good σ donor, and the adjacent, stabilizing heteroatoms enrich the π system with such electrons as to inhibit Pi backbonding. Enders
and Hermann
Molecules containing two and three carbene moieties have been prepared as potential bidentate and tridentate carbene ligands.
X-ray structures of imidazolic carbenes show N–C–N bond angles of 103–110°, but typically 104°. 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 is 121°. Contrariwise, monoamino carbenes X-ray structures have shown N–C–X bond angles of around 104° and 109° respectively.
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.
Ag(I)-NHC complexes have been widely tested for their biological applications.
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. 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 or .
Alternate techniques have been developed to avoid such purification difficulties.
Imidazol-2-ylidenes and dihydroimidazol-2-ylidenes, such as IMes, have been prepared by the deprotonation of the respective imidazolium and imidazoline salts. Acyclic carbenes and tetrahydropyrimidinyl-based carbenes 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.
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, because they are too nucleophilic and often act as hydridic reductants:
In principle, Sodium hydride or potassium hydride would be the ideal base for deprotonating these precursor salts, but in practice the salt dissolves too slowly for effective reaction. DMSO or Tert-Butanol catalyze the reaction through the soluble tert-butoxide or dimsyl sodium bases, but those compounds are too nucleophilic for non-aromatic carbenes.
Deprotonation with sodium or potassium hydride in a mixture of liquid ammonia/tetrahydrofuran at −40 °C has been reported for imidazole-based carbenes, and Arduengo and coworkers 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.
Lithium amides like the diisopropylamide (LDA) and tetramethylpiperidide (LiTMP) generally work well for the deprotonation of all types of salts, providing that not too much LiOH impurity is present. Metal hexamethyldisilazides deprotonate almost all salts cleanly, except for unhindered formamidinium salts, where this base can act as a nucleophile to give a triaminomethane adduct.
A single example of deoxygenation a urea with a fluorene derived carbene to give the tetramethyldiaminocarbene and fluorenone has also been reported:
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. For example:
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 Monocrystal 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 °C.
[[File:Air-free sublimation.png|thumb|600x600px|Apparatus:
For a review on the physico-chemical properties (electronics, sterics, ...) of N-heterocyclic carbenes:
Dechalcogenation and dechlorination
For carbenes stable at elevated temperatures, a rare approach desulfurisation in THF with molten potassium:
A contributing factor to the reaction's success is that the potassium sulfide byproduct is insoluble in the solvent.
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 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:
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.
Method (steps 4 and 5 can be repeated as required; steps 6 and 7 are not essential):
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Further reading
Reviews on persistent carbenes:
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