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) (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 derivied from vitamin B1 (thiamine), was the catalyst involved in the benzoin condensation that yields furoin from furfural. 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:
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.
Isolation In 1970, Wanzlick's group generated imidazol-2-ylidene carbenes by the deprotonation of an imidazolium salt. Wanzlick as well as Roald Hoffmann, 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:
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 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 °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.
New examples and new theory
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.
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 bond lengths 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 prevent reaction 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 heteroatoms 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.
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). 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.
Diaminocarbenes A wide variety of bisazomethine ylides are known, both cyclic and acylic:
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:
Imidazol-2-ylidenes Imidazol-2-ylidenes are known with alkyl, aryl, alkyloxy, alkylamino, alkylphosphino and even chiral substituents on the nitrogen atoms.
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 induction through the σ system.
Because imidazolylidenes are stable against dimerization, molecules can contain multiple imidazol-2-ylidene groups:
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:
Few such carbenes have been reported, but a triphenyl molecule is commercially available:
Monoaminocarbenes The non-nitrogen atom adjacent to the carbene may be carbon (the cyclic monoamino carbenes), oxygen, sulfur, or phosphorus:
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:
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.
Bertrand's carbenes In Bertrand's persistent carbenes, the unsaturated carbon is bonded to a phosphorus and a silicon. However, these compounds exhibit some alkynic properties and may instead be a hypervalent phosphaalkyne. The exact nature of these red oils remained unclear .
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. Metal (Pb, Pd, Pt) substituted triplet carbenes (metalla-carbenes) are only stable in the cold.
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 nm light in benzene with expulsion of nitrogen gas.
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 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°).
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. have performed a range of organic reactions involving a model triazol-5-ylidene:
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 pKa ≈ 24 in dimethyl sulfoxide (DMSO):
Conjugate pKa 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 pKa 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 biomimetic descendant, the Stetter reaction.
Dimerisation At one time, stable carbenes were thought to reversibly dimerise through the so-called Wanzlick equilibrium. The uncatalyzed reaction is typically slow, 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:
Protons, which create formamidinium salts, catalyze the reaction, as do other Lewis acids.