Chapter 5

Carbocations, Carbanions, Free Radicals, Carbenes, and Nitrenes

There are four types of organic species in which a carbon atom has a valence of only 2 or 3.¹ They are usually very short-lived, and most exist only as intermediates that are quickly converted to more stable molecules. However, some are more stable than others and fairly stable examples have been prepared for three of the four types. The four types of species are carbocations (A), carbon radicals (B), carbanions (C), and carbenes (D). Of the four, only carbanions have a complete octet around the carbon. There are many other organic ions and radicals with charges and unpaired electrons on atoms other than carbon, but only nitrenes (E), the nitrogen analogues of carbenes, will be discussed. Each of these five types is discussed in a separate section, which in each case includes brief summaries of the ways in which the species form and react. These summaries are short and schematic. The generation and fate of the five types are more fully treated for the appropriate specific reactions in Part II.

5.A. Carbocations2

5.A.i. Nomenclature

First, the nomenclature of carbocations (A) is discussed. For many years, these species were called “carbonium ions,” although it was suggested³ as long ago as 1902 that this was inappropriate because “-onium” usually refers to a covalency higher than that of the neutral atom. Nevertheless, the name “carbonium ion” was well established and created few problems⁴ until some years ago, when Olah and co-workers^2,5 found evidence for another type of intermediate in which there is a positive charge at a carbon atom, but in which the formal covalency of the carbon atom is five rather than three. The simplest example is the methanonium ion (CH₅⁺; see Reaction 12-01). Olah⁵ proposed that the name “carbonium ion” be henceforth reserved for pentacoordinated positive ions, and that A be called a “carbenium ions.” He also proposed the term “carbocation” to encompass both types. IUPAC has accepted these definitions.⁶ For the most part, intermediates such as A are called carbenium ions or carbocations, but the latter term will be used more often in this book.

5.A.ii. Stability and Structure of Carbocations

[Reprinted with permission from Kato, T.; Reed, C.A. Angew. Chem. Int. Ed. 2004, 43, 2908, Wiley–VCH Verlag GmbH & Co. KGaA, Weinheim. Copyright © 2004 by Wiley–VCH Verlag]

Carbocations are intermediates in several kinds of reactions.⁷ The more stable ones have been prepared in solution and in some cases even as solid salts. X-ray crystallographic structures also have been obtained in some cases.⁸ The X-ray of the tert-butyl cation complexed with dichloromethane was reported,⁹ for example, and is presented as 1 with the solvent molecules removed for clarity. The IR spectrum of the tert-butyl cation has been recorded in the gas phase.¹⁰ An isolable dioxa-stabilized pentadienylium ion was isolated and its structure was determined by NMR, NMR, mass spectrometry, and IR.¹¹ A β-fluoro substituted 4-methoxyphenethyl cation has been observed directly by laser flash photolysis.¹² In solution, the carbocation may be free (this is more likely in polar solvents, in which it is solvated) or it may exist as an ion pair,¹³ which means that it is closely associated with a negative ion, called a counterion or gegenion. Ion pairs are more likely in nonpolar solvents.

Among simple alkyl carbocations,¹⁴ the order of stability is tertiary > secondary > primary. There are many known examples of rearrangements of primary or secondary carbocations to tertiary, both in solution and in the gas phase (see Sec. 18.A.ii). Since simple alkyl cations are unstable in ordinary strong-acid solutions (e.g., H₂SO₄), the study of these species was greatly facilitated by the discovery that many of them could be kept indefinitely as stable solutions in mixtures of fluorosulfuric acid and antimony pentafluoride. Such mixtures, usually dissolved in SO₂ or SO₂ClF, are among the strongest acidic solutions known and are often called superacids.¹⁵ The original experiments involved the addition of alkyl fluorides to SbF₅.¹⁶

Subsequently, it was found that the same carbocations could also be generated from alcohols in superacid–SO₂ at −60 °C¹⁷ and from alkenes by the addition of a proton from superacid or HF–SbF₅ in SO₂ or SO₂ClF at low temperatures.¹⁸ Even alkanes give carbocations in superacid by loss of H⁻. For example,¹⁹ 2-methylpropane gives the tert-butyl cation.

No matter how they are generated, study of the simple alkyl carbocations has provided dramatic evidence for the stability order.²⁰ Both propyl fluorides gave the isopropyl cation; all four butyl fluorides²¹ gave the tert-butyl cation, and all seven of the pentyl fluorides examined gave the tert-pentyl cation. n-Butane, in superacid, gave only the tert-butyl cation. To date, no primary cation has survived long enough for detection. Neither methyl nor ethyl fluoride gave the corresponding carbocations when treated with SbF₅. At low temperatures, methyl fluoride gave chiefly the methylated sulfur dioxide salt [(CH₃OSO)⁺SbF₆⁻],²² while ethyl fluoride rapidly formed the tert-butyl and tert-hexyl cations by addition of the initially formed ethyl cation to ethylene molecules also formed.²³ At room temperature, methyl fluoride also gave the tert-butyl cation.²⁴ In accord with the stability order, hydride ion is abstracted from alkanes by superacid most readily from tertiary and least readily from primary positions.

The stability order can be explained by the polar effect and by hyperconjugation (Sec. 2.M). In the polar effect, nonconjugated substituents exert an influence on stability through bonds (inductive effect) or through space (field effect). Since a tertiary carbocation has more carbon substituents on the positively charged carbon, relative to a primary, there is a greater polar effect that leads to great stability. In the hyperconjugation explanation,²⁵ a primary carbocation is compared with a tertiary, and “the hyperconjugation concept arises from model-building procedures (see Sec. 2.M). In general, this means that the model must be corrected by including some delocalization in order to get a good enough description.”²⁶ Evidence used to support the hyperconjugation explanation is that the equilibrium constant for this reaction involving 2 and 3 is 1.97, showing that 3 is more stable than 2.²⁷ Due to a β secondary isotope effect, there is less hyperconjugation in 2 than in 3 (see Sec. 6.J.V.ii for isotope effects).²⁸ The field effect explanation is that the electron-donating effect of alkyl groups increases the electron density at the charge-bearing carbon, reducing the net charge on the carbon, and in effect spreading the charge over the α carbons. It is a general rule that the more concentrated any charge is, the less stable the species bearing it will be. There are several structural types of delocalization, as summarized in Table 5.1.²⁹

Table 5.1 Structural Types of Delocalization^a

Valence Structures	Abbreviation	Name
	ππ	Simple conjugation
	σπ	Hyperconjugation
	πσ	Homoconjugation
	σσ	Homohyperconjugation
	σπ/ππ	Hyperconjugation/conjugation
	σπ/σπ	Double hyperconjugation
[Reprinted with permission from Radom, L.; Poppinger, D.; Haddon, R.C. in Olah, G.A.; Schleyer, P.v.R. Carbonium Ions, Vol. 5, Wiley, NY, 1976, pp. 2303–2426, Wiley–VCH Verlag GmbH & Co. KGaA, Weinheim. Copyright © 1976 by Wiley–VCH Verlag].
a. See Ref. 25.

The most stable of the simple alkyl cations is the tert-butyl cation. Even the relatively stable tert-pentyl and tert-hexyl cations fragment at higher temperatures to produce the tert-butyl cation, as do all other alkyl cations with four or more carbons to date studied.³⁰ Methane,³¹ ethane, and propane, in superacid, also yield tert-butyl cations as the main product (see Reaction 12-20). Even paraffin wax and polyethylene give a tert-butyl cation. Solid salts of tert-butyl and tert-pentyl cations, [e.g., Me₃C⁺ SbF₆⁻], have been prepared from superacid solutions and are stable below −20 °C.³²

In carbocations, where the positive carbon is in conjugation with a double bond, as in allylic cations (the allyl cation is 4, R = H), the stability is greater because of increased delocalization due to resonance³³ where the positive charge is spread over several atoms instead of being concentrated on one (see the molecular orbital picture of 4 in Sec. 2.C, category 2). Each of the terminal atoms in 4 has a charge of (the charge is exactly if all of the R groups are the same). Stable cyclic and acyclic allylic-type carbocations³⁴ have been prepared by dissolving conjugated dienes in concentrated sulfuric acid; the cyclopentadienyl cation, (5) is an example.³⁵

Stable allylic carbocations have also been obtained by the reaction between alkyl halides, alcohols, or alkenes (by hydride extraction) and SbF₅ in SO₂ or SO₂ClF.³⁶ Bis(allylic) cations³⁷ are more stable than the simple allylic type, and some of these have been prepared in concentrated sulfuric acid.³⁸ Arenium ions (Sec. 11.A.i) are familiar examples of this type. Propargyl cations (RCCC⁺R₂) have also been prepared.³⁹

Canonical forms can be drawn for benzylic carbocations, as shown,⁴⁰ and they are similar to those shown above for allylic cations.

A number of benzylic carbocations have been obtained in solution as SbF₆⁻ salts.⁴¹ Diarylmethyl and triarylmethyl cations are even more stable because more canonical forms are possible (i.e., there is more extensive delocalization, hence greater stability). Chlorotriphenylmethane ionizes in polar solvents to give the stable triphenylmethyl cation (trityl cation, see 18), for example, because the solvent does not react with the ion,

whereas water does react with the ion. In liquid SO₂, for example, the ion remains stable for many years. Both triphenylmethyl and diphenylmethyl cations have been isolated as solid salts.⁴² In fact, Ph₃C⁺ BF₄⁻ and related salts are available commercially. Arylmethyl cations are further stabilized if they have electron-donating substituents in ortho or para positions.⁴³ Dications⁴⁴ and trications are also possible, including the particularly stable dication (6), where each positively charged benzylic carbon is stabilized by two azulene rings.⁴⁵ A related trication is known where two azulene rings stabilize each benzylic cationic center.⁴⁶

Cyclopropylmethyl carbocations⁴⁷ are even more stable than benzylic carbocations. Carbocations 7, 8, and similar ions have been prepared by dissolution of the alcohols in FSO₃H–SO₂–SbF₅,^{48 and 9 has been prepared from the corresponding alcohol in 96% H₂SO₄.49 This special stability, which increases with each additional cyclopropyl group, is}

a result of conjugation between the bent orbitals of the cyclopropyl rings (Sec. 4.Q.i) and the vacant p orbital of the cationic carbon (see 10). Nuclear magnetic resonance and other studies have shown that the vacant p orbital lies parallel to the C-2–C-3 bond of the cyclopropane ring and not perpendicular to it.⁵⁰ In this respect, the geometry is similar to that of a cyclopropane ring conjugated with a double bond (Sec. 4.Q.i). Cyclopropylmethyl cations are further discussed in Section 10.C.i, category 4. The stabilizing effect just discussed is unique to cyclopropyl groups. Cyclobutyl and larger cyclic groups are about as effective at stabilizing a carbocation as ordinary alkyl groups.⁵¹

Another structural feature that increases carbocation stability is the presence, adjacent to the cationic center, of a heteroatom bearing an unshared pair⁵² (e.g., oxygen,⁵³ nitrogen,⁵⁴ or halogen).⁵⁵ Such ions are stabilized by resonance, as with the oxocarbenium ion (R₂C=O⁺Me).

This methoxymethyl cation can be obtained as a stable solid, MeOCH₂⁺ SbF₆⁻.⁵⁶ Carbocations containing either α, β, or γ silicon atom are also stabilized,⁵⁷ relative to similar ions without the silicon atom. γ-Silyl cyclobutylcarbocations are known.⁵⁸ In superacid solution, ions [e.g., CX₃⁺ (X = Cl, Br, I)] have been prepared.⁵⁹ Vinyl-stabilized halonium ions are also known.⁶⁰

Simple acyl cations (RCO⁺) have been prepared⁶¹ in solution and the solid state.⁶² The acetyl cation (CH₃CO⁺) is about as stable as the tert-butyl cation (see Table 5.1). The 2,4,6-trimethylbenzoyl and 2,3,4,5,6-pentamethylbenzoyl cations are especially stable (for steric reasons) and are easily formed in 96% H₂SO₄.⁶³ These ions, often referred to as acylium ions, are stabilized by a canonical form containing a triple bond (12), although the positive charge is principally located on the carbon,⁶⁴ so that 11 contributes more than 12.

The stabilities of many other stable carbocations can also be attributed to resonance. Among these are the tropylium, cyclopropenium,⁶⁵ and other aromatic cations discussed in Chapter 2. Where resonance stability is completely lacking, as in the phenyl (C₆H₅⁺) or vinyl cations,⁶⁶ the ion, if formed at all, is usually very short lived.⁶⁷ Neither a vinyl⁶⁸ nor a phenyl cation has as yet been prepared as a stable species in solution.⁶⁹ However, stable alkenyl carbocations have been generated on Zeolite Y,⁷⁰ and the phenyl cation has been observed in cryogenic argon matrices.⁷¹

Various quantitative methods have been developed to express the relative stabilities of carbocations.⁷² One of the most common of these, although useful only for relatively stable carbocations that are formed by ionization of alcohols in acidic solutions, is based on the equation⁷³

pK_R+ is the pK value for the reaction and is a measure of the stability of the carbocation. The H_R parameter is an easily obtainable measurement of the stability of a solvent (Sec. 8.C) and approaches pH at low concentrations of acid. In order to obtain pK_R+, for a cation R⁺, one dissolves the alcohol ROH in an acidic solution of known H_R. Then, the concentration of R⁺ and ROH are obtained, generally from spectra, and pK_R+ is easily calculated.⁷⁴ A measure of carbocation stability that applies to less stable ions is the dissociation energy [D(R⁺–H⁻)] for the cleavage reaction R–H → R⁺ + H⁻, which can be obtained from PES (Sec. 1.E) and other measurements. Some values of D(R⁺–H⁻) are shown in Table 5.2.^{75–7875767778} Within a given class of ion, (primary, secondary, allylic, aryl, etc.), D(R⁺–H⁻) has been shown to be a linear function of the logarithm of the number of atoms in R⁺, with larger ions being more stable.⁷⁷

Table 5.2 R–H → R⁺ + H⁻ Dissociation Energies in the Gas Phase.

Since the central carbon of tricoordinated carbocations has only three bonds and no other valence electrons, the bonds are sp² and should be planar.⁷⁹ Raman, IR, and NMR spectroscopic data on simple alkyl cations show this to be so.⁸⁰ In methylcycohexyl cations, there are two chair conformations where the carbon bearing the positive charge is planar (13 and 14), and there is evidence that 14 is more stable due to a difference in hyperconjugation.⁸¹ Arenonium ions (15) are also known, and are relatively stable.⁸² Other evidence is that carbocations are difficult to form at bridgehead atoms in [2.2.1] systems,⁸³ where they cannot be planar (see Sec. 10.A.ii).⁸⁴ Bridgehead carbocations are known, however, as in [2.1.1]hexanes⁸⁵ and cubyl carbocations.⁸⁶ However, larger bridgehead ions can exist. For example, the adamantyl cation (15) has been synthesized, as the SF₆⁻ salt.⁸⁷ The relative stability of 1-adamantyl cations is influenced by the number and nature of substituents. For example, the stability of the 1-adamantyl cation increases with the number of isopropyl substituents at C-3, C-5, and C-7.⁸⁸ Among other bridgehead carbocations that have been prepared in superacid solution at –78 °C are the dodecahydryl cation (16)⁸⁹ and the 1-trishomobarrelyl cation (17).⁹⁰ In the latter case, the instability of the bridgehead position is balanced by the extra stability gained from the conjugation with the three cyclopropyl groups.

Triarylmethyl cations (e.g., the triphenylmethyl carbocation, 18),⁹¹ are propeller-shaped, although the central carbon and the three ring carbons connected to it are in a plane:⁹² The three benzene rings cannot be all in the same plane due to steric hindrance, although increased resonance energy would be gained if they could.

An important tool for the investigation of carbocation structure is measurement of the NMR chemical shift of the carbon atom bearing the positive charge.⁹³ This shift approximately correlates with electron density on the carbon. The chemical shifts for a number of ions are given in Table 5.3.⁹⁴ As shown in Table 5.3, the substitution of an ethyl for a methyl or a methyl for a hydrogen atom causes a downfield shift, indicating that the central carbon becomes somewhat more positive. On the other hand, the presence of hydroxy or phenyl groups decreases the positive character of the central carbon. The chemical shifts are not always in exact order of carbocation stabilities, as determined in other ways. Thus the chemical shift shows that the triphenylmethyl cation has a more positive central carbon than diphenylmethyl cation, although the former is more stable. Also, the 2-cyclopropylpropyl and 2-phenylpropyl cations have shifts of −86.8 and −61.1, respectively, although we have seen that according to other criteria a cyclopropyl group is better than a phenyl group at stabilizing a carbocation.⁹⁵ The reasons for this discrepancy are not fully understood.⁸⁸,⁹⁶

Table 5.3 The NMRChemical-Shift Values, in Parts per Million from S₂, for the Charged Carbon Atom of Some Carbocations in SO₂ClF–SbF₅, SO₂–FSO₃H–SbF₆, or SO₂–SbF₅^a

Nonclassical carbocations are discussed in section 10.C.i.

5.A.iii. The Generation and Fate of Carbocations

A number of methods are available to generate carbocations, stable or unstable.

1. A direct ionization, in which a leaving group attached to a carbon atom leaves with its pair of electrons, as in solvolysis reactions of alkyl halides (see Sec. 10.G.i) or sulfonate esters (Reaction 10-04):

2. Ionization after an initial reaction that converts one functional group into a leaving group, as in protonation of an alcohol to give an oxonium ion (ROH₂⁺) or conversion of a primary amine to a diazonium salt, both of which ionize to the corresponding carbocation:

Oxonium ions are also generated by protonation of ethers,⁹⁷ including epoxides.⁹⁸ However, these ions do not always lead to carbocations via ionization, but often undergo substitution reactions (see Chap 10). Oxatriquinane, (19) is a fused, tricyclic alkyl oxonium ion that is remarkably stable. Oxonium ion 19 has been heated to reflux in water, can be chromatographed, and does not react with alcohols or alkyl thiols.⁹⁹ The X-ray crystal structure shows longer C–O bond distances and more acute C–O–C bond angles than any reported alkyloxonium salt. Oxatriquinene (20) has also been synthesized.

3. A proton or other positive species adds to one atom of an alkene or alkyne, leaving the adjacent carbon atom with a positive charge (see Chapters 11 and 15).

4. A proton or other positive species adds to one atom of a C=X bond, where X = O, S, N in most cases, leaving the adjacent carbon atom with a positive charge (see Chapter 16). When X = O, S, this ion is a resonance stabilized oxocarbenium ion (X = O) or thiacarbenium ion (X = S), as shown. When X = NR, protonation leads to an iminium ion (X = N), with the charge localized on the nitrogen. A silylated carboxonium ion (e.g., 21) has been reported.¹⁰⁰

When formed by any of the processes 1–3, carbocations are most often short-lived transient species and react further without being isolated. Oxocarbenium ions are more stable and may be longer lived, but even oxocarbenium ions are transient intermediates. The intrinsic barriers to formation and reaction of carbocations have been studied.¹⁰¹

There are two principal pathways by which carbocations react to give stable products that are effectively the reverse of the two pathways just described.

1. A carbocation may combine with a species possessing an electron pair (essentially a Lewis acid–base reaction, see Chapter 8). This reaction occurs by an atom or group donating electrons to the positive carbon of the carbocation. The atom or group that donates the electrons to carbon is called a nucleophile (see Chapter 10):

Any reasonable nucleophile will react with the carbocation, but the nucleophile may also be a neutral species with a pair to donate, in which case, of course, the immediate product must bear a positive charge (see Chapters 10, 13, 15, and 16). These reactions are very fast. A recent study measured k_s (the rate constant for reaction of a simple tertiary carbocation) to be 3.5 × 10¹² s⁻¹.¹⁰²

2. The carbocation may have a proton (or much less often, another positive ion) removed from the adjacent atom (see Chapters 11 and 17):

Carbocations can also adopt two other pathways that lead not to stable products, but to other carbocations:

3. Rearrangement. An alkyl or aryl group or a hydrogen atom (sometimes another group) migrates with its electron pair to the positive center, leaving another positive charge behind (see Chap 18):

A novel rearrangement has been observed. The 2-methyl-2-butyl-1-¹³C cation (¹³C-labeled tert-amyl cation) shows an interchange of the inside and outside carbons with a barrier of 19.5 kcal mol⁻¹ (81.6 kJ mol⁻¹) (±2.0 kcal mol⁻¹, 8.4 kJ mol⁻¹).¹⁰³ Another unusual migratory process has been observed for the nonamethylcyclopentyl cation. It has been shown that “four methyl groups undergo rapid circumambulatory migration with a barrier <2 kcal mol⁻¹ (8.4 kJ mol⁻¹) while five methyl groups are fixed to ring carbons. The process that equalizes the two sets of methyls has a barrier of 7.0 kcal mol⁻¹ (29.3 kJ mol⁻¹).”¹⁰⁴

4. Addition. A carbocation may add to a double bond, generating a positive charge at a new position (see Chaps 11 and 15). This means that the π bond donates two electrons to a positive atom, generating positive charge on the carbon as shown:

Whether formed by pathway 3 or 4, the new carbocation normally reacts further in an effort to stabilize itself, usually by pathway 1 or 2. However, 22 can add to another alkene molecule, and this product can add to still another, and so on. This is one of the mechanisms for vinyl polymerization.

5.B. Carbanions

5.B.i. Stability and Structure105

Formally, a carbanion is a trivalent carbon atom with an unshared electron pair, and a formal charge of −1. In fact, there are few carbanions that do not have an anion-stabilizing group attached to the carbon atom. Stabilization may be by resonance delocalization or by orbital participation of an atom with d orbitals or orbitals associated withy a metal.

By definition, every carbanion possesses an unshared pair of electrons and is formally a base. When a carbanion donates an electron to a proton, it is converted to its conjugate acid (an acid–base reaction, see Chapter 8). If the carbanion (R₃C:⁻) were available, reaction with an acid generates the conjugate acid (R₃C–H), an alkane. The stability of the carbanion is directly related to the strength of the conjugate acid. The weaker that conjugate acid, the greater the base strength of the carbanion, and the lower the stability of the carbanion.¹⁰⁶ Stability here is judged by diminished reactivity (lower electron-donating ability) with a proton. The greater the stability, the lower the electron-donating ability (lower reactivity) for reaction of the carbanion with a proton (any acid that is sufficiently strong), and hence the longer lived the carbanion. Thus the determination of the order of stability of a series of carbanions is equivalent to a determination of the inverse order of strengths of the conjugate acids, and one can obtain information about relative carbanion stability from a table of acid strengths (e.g., Table 8.1).

While formation of simple carbanions (e.g, CH₃⁻) is rare, formation of a carbon–metal bond often generates a molecule (e.g., R₃C–M, where M = a metal atom) that has a polarized bond in which the carbon is electron rich (δ⁻). An organic molecule that contains a carbon–metal bond is called an organometallic compound. Organometallic compounds where the metal is Mg, Li, or other metals are carbanion surrogates, and in much of their chemistry they react as if they were carbanions (see Reactions 12-22–12.39). Many such compounds are known, and organometallic chemistry is a very large area, occupying a borderline region between organic and inorganic chemistry. This section will discuss carbanions with little reference to a metal. Section 5.B.ii will discuss the structures of organometallic compounds, which are often carbanion surrogates.

Carbanions are very strong bases, and the conjugate acids of simple unsubstituted carbanions are very weak acids, with very few exceptions. Unfortunately, it is not easy to measure acid strengths of very weak acids. There is little doubt that carbanions are very unstable in solution, and in contrast to the situation with carbocations, efforts to prepare solutions in which carbanions (e.g., ethyl or isopropyl) exist in a relatively free state have not yet been successful. It has also not been possible to form these carbanions in the gas phase. Indeed, there is evidence that simple carbanions (e.g., ethyl and isopropyl) are unstable, losing an electron, which converts them to radicals.¹⁰⁷ Nevertheless, there have been several approaches to the problem. Applequist and O'Brien¹⁰⁸ studied the position of equilibrium for the reaction:

This reaction was done in ether or an ether–pentane mixture. The reasoning in these experiments was that the R group that forms the more stable carbanion would be more likely to be bonded to lithium than to iodine. Carbanion stability was found to be in the order: vinyl > phenyl > cyclopropyl > ethyl > n-propyl > isobutyl > neopentyl > cyclobutyl > cyclopentyl. In a somewhat similar approach, Dessy et al.¹⁰⁹ treated a number of alkylmagnesium compounds with a number of alkylmercury compounds in THF, setting up the equilibrium:

where the group of greater carbanion stability is linked to magnesium. The carbanion stability determined this way was phenyl > vinyl > cyclopropyl > methyl > ethyl > isopropyl. The two stability orders are in fairly good agreement, and they show that stability of simple carbanions decreases in the order methyl > primary > secondary. It was not possible to determine the position of tert-butyl by the experiments reported by Dessy et al.¹⁰⁹, but there seems little doubt that it is still less stable. This stability order can be interpreted as solely a consequence of the field effect since resonance is absent. The electron-donating alkyl groups of isopropyl result in a greater negative charge density at the central carbon atom (compared with methyl), thus decreasing its stability. The results of Applequist and O'Brien¹⁰⁸ show that β branching also decreases carbanion stability. Cyclopropyl occupies an apparently anomalous position, but this is probably due to the large amount of s character in the carbanionic carbon (see Sec. 5.B.i, category 2). Strongly electron-withdrawing groups (e.g., trifluoromethylsulfonyl) provide exceptional stability to carbanions.¹¹⁰

A different approach to the problem of hydrocarbon acidity, and hence carbanion stability, is that of Shatenshtein and Shapiro, who treated hydrocarbons with deuterated potassium amide and measured the rates of hydrogen exchange.¹¹¹ The experiments did not measure thermodynamic acidity, since rates were measured, not positions of equilibria. They measured kinetic acidity; that is, which compounds gave up protons most rapidly (see Sec. 6.F for the distinction between thermodynamic and kinetic control of product). Measurements of rates of hydrogen exchange enable one to compare acidities of a series of acids against a given base even where the positions of the equilibria cannot be measured because they lie too far to the side of the starting materials; that is, where the acids are too weak to be converted to their conjugate bases in measurable amounts. Although the correlation between thermodynamic and kinetic acidity is far from perfect,¹¹² the results of the rate measurements, too, indicated that the order of carbanion stability is methyl > primary > secondary > tertiary.¹¹¹

Experiments described above were done in solution, and experiments in the gas phase gave different results. In reactions of ⁻OH with alkyltrimethylsilanes, it is possible to cleave either R or Me. Since the R or Me come off as a carbanion or incipient carbanion, the product ratio RH/MeH can be used to establish the relative stabilities of various R groups. From these experiments a stability order of neopentyl > cyclopropyl > tert-butyl > n-propyl > methyl > isopropyl > ethyl was found.¹¹³ On the other hand, in a different kind of gas-phase experiment, Graul and Squires¹¹⁴ were able to observe CH₃⁻ ions, but not the ethyl, isopropyl, or tert-butyl ions.

As mentioned above, carbanion-stabilizing groups can increase the stability of carbanions, which influences their ease of formation. Six structural features that lead to improved stability are listed:

1. Conjugation of the Unshared Pair with an Unsaturated Bond

In cases where a double or triple bond is located α to the carbanionic carbon, the ion is stabilized by resonance in which the unshared pair overlaps with the π electrons of the double bond. This factor is responsible for the stability of the allylic¹¹⁵ and benzylic¹¹⁶ types of carbanions:

Diphenylmethyl and triphenylmethyl anions are still more stable due to extensive delocalization into the benzene rings, and can be kept in solution indefinitely if water is rigidly excluded.¹¹⁷ X-ray crystallographic structures have been obtained for Ph₂CH⁻ and Ph₃C⁻ enclosed in crown ethers.¹¹⁸ Carbanion 23 has a lifetime of several minutes (hours in a freezer at −20 °C) in dry THF.¹¹⁹ Condensed aromatic rings fused to a cyclopentadienyl anion are known to stabilize the carbanion.¹²⁰

Where the carbanionic carbon is conjugated with a carbon–oxygen or carbon–nitrogen multiple bond (Y = O or N), the stability of the ion is greater than that of the triarylmethyl anions, since these electronegative atoms are more capable of bearing a negative charge than carbon. However, it is questionable whether ions of this type should be called a carbanion at all, since in the case of enolate ions, for example, 25 contributes more to the hybrid than 24 although such ions react more often at the carbon than at the oxygen. In benzylic enolate anions (e.g., 26), the conformation of the enolate can be coplanar with the aromatic ring or bent out of plane if the strain is too great.¹²¹ Enolate ions can also be maintained in solution in many cases, at least for minutes or hours at lower temperatures. In the case of carbanions at a carbon α to a nitrile, the “enolate” resonance form would be a ketene imine nitranion, but the existence of this species has been called into question.¹²² A nitro group is particularly effective in stabilizing a negative charge on an adjacent carbon, and the anions of simple nitro alkanes can exist in water. Thus the pK_a for nitromethane is 10.2. Dinitromethane is even more acidic (pK_a = 3.6). In contrast to the stability of cyclopropylmethyl cations (Sec. 5.A.ii), the cyclopropyl group exerts only a weak stabilizing effect on an adjacent carbanionic carbon.¹²³

By combining a very stable carbanion with a very stable carbocation, Okamoto et al.¹²⁴ were able to isolate the salt (27), as well as several similar salts, as stable solids. These are salts that consist entirely of carbon and hydrogen atoms.

2. Carbanions Increase in Stability with an Increase in the Amount of s Character at the Carbanionic Carbon. Thus the order of stability is

Acetylene, where the carbon is sp hybridized with 50% s character, is much more acidic than ethylene¹²⁵ (sp², 33% s), which in turn is more acidic than ethane, with 25% s character. Increased s character means that the electrons are closer to the nucleus, and hence of lower energy. As previously mentioned, cyclopropyl carbanions are more stable than methyl, owing to the larger amount of s character as a result of strain (see Sec. 4.Q.i).

3. Stabilization by Sulfur¹²⁶ or Phosphorus. Attachment to the carbanionic carbon of a sulfur or phosphorus atom causes an increase in carbanion stability, although the reasons for this are in dispute. One theory is that there is overlap of the unshared pair with an empty d orbital¹²⁷ (pπ–dπ bonding, see Sec. 2.H). For example, a carbanion containing the SO₂R group would be written as follows:

However, there is evidence against d-orbital overlap; and the stabilizing effects have been attributed to other causes.¹²⁸ In the case of a PhS substituent, carbanion stabilization is thought to be due to a combination of the inductive and polarizability effects of the group, and d–pπ resonance and negative hyperconjugation play a minor role, if any.¹²⁹ An α silicon atom also stabilizes carbanions.¹³⁰

4. Field Effects. Most of the groups that stabilize carbanions by resonance effects (either the kind discussed in paragraph 1 above or the kind discussed in paragraph 3) have electron-withdrawing field effects and thereby stabilize the carbanion further by spreading the negative charge, although it is difficult to separate the field effect from the resonance effect. However, in a nitrogen (ylid R₃N⁺–CR₂, see Sec. 2.H), where a positive nitrogen is adjacent to the negatively charged carbon, only the field effect operates. Ylids are more stable than the corresponding simple carbanions. Carbanions are stabilized by a field effect if there is any heteroatom (O, N, or S) connected to the carbanionic carbon, provided that the heteroatom bears a positive charge in at least one important canonical form,¹³¹ for example,

5. Certain Carbanions Are Stable because They Are Aromatic. See the cyclopentadienyl anion in Section 2.I.ii, and other aromatic anions in Chapter 2.

6. Stabilization by a Nonadjacent π Bond.¹³² In contrast to the situation with carbocations (see Sec. 2.C.i), there have been fewer reports of carbanions stabilized by interaction with a nonadjacent π bond. One that may be mentioned is 30, formed when optically active camphenilone (28) was treated with a strong base (potassium tert-butoxide).¹³³ That 30 was truly formed was shown by the following facts: (1) A proton was abstracted: ordinary CH₂ groups are not acidic enough for this base; (2) recovered 28 was racemized: 30 is symmetrical and can be attacked equally well from either side; (3) when the experiment was performed in deuterated solvent, the rate of deuterium uptake was equal to the rate of racemization; and (4) recovered 28 contained up to three atoms of deuterium per molecule, although if 29 were the only ion, no more than two could be taken up. Ions of this type, in which a negatively charged carbon is stabilized by a carbonyl group two carbons away, are called homoenolate ions.

Based on these four categories, functional groups in the α position stabilize carbanions in the following order: NO₂ > RCO > COOR > SO₂ > CN ~ CONH₂ > halogen > H > R.

It is unlikely that free carbanions exist in solution, although some of the stabilized carbanions noted above have reasonable lifetimes in solution. Like carbocations, they usually exist as either ion pairs or they are solvated.¹³⁴ Among experiments that demonstrate ion pairing or solvation was the treatment of PhCOCHMe^– M⁺ with ethyl iodide, where M⁺ was Li⁺, Na⁺, or K⁺. The half-lives of the reaction were¹³⁵ for Li, 31 × 10⁻⁶; Na, 0.39 × 10⁻⁶; and K, 0.0045 × 10⁻⁶, demonstrating that the species involved were not identical. Similar results¹³⁶ were obtained with Li, Na, and Cs triphenylmethides (Ph₃C⁻ M⁺).¹³⁷ Where ion pairs are unimportant, carbanions are solvated. Cram¹⁰⁵ demonstrated solvation of carbanions in many solvents. There may be a difference in the structure of a carbanion depending on whether it is free (e.g., in the gas phase) or in solution. The negative charge may be more localized in solution in order to maximize the electrostatic attraction to the counterion.¹³⁸

The structure of simple unsubstituted carbanions is not known with certainty since they have not been isolated, but it is likely that the central carbon is sp³ hybridized, with the unshared pair occupying one apex of the tetrahedron. Carbanions are expected to have pyramidal structures (e.g., 31, similar to those of amines.

The methyl anion (CH₃⁻) has been observed in the gas phase and reported to have a pyramidal structure.¹³⁹ If this is taken as a general structure for carbanions, then any carbanion in which the three R groups are different should be chiral and reactions in which it is an intermediate should give retention of configuration. Attempts have been made to demonstrate this principle, but without success.¹⁴⁰ A possible explanation is that pyramidal inversion takes place here, as in amines, so that the unshared pair and the central carbon rapidly oscillate from one side of the plane to the other. There is, however, other evidence for the sp³ nature of the central carbon and for its tetrahedral structure. Carbons at bridgeheads, although extremely reluctant to undergo reactions in which they must be converted to carbocations, easily undergo reactions in which they must be carbanions and stable bridgehead carbanions are known.¹⁴¹ Also, reactions at vinylic carbons proceed with retention,¹⁴² indicating that the intermediate 32 has sp² hybridization and not the sp hybridization that would be expected in the analogous carbocation. A cyclopropyl anion can also hold its configuration.¹⁴³

Carbanions in which the negative charge is stabilized by resonance involving overlap of the unshared-pair orbital with the π electrons of a multiple bond are essentially planar, as would be expected by the necessity for planarity in resonance, although unsymmetrical solvation or ion-pairing effects may cause the structure to deviate somewhat from true planarity.¹⁴⁴ Cram¹⁴⁴ showed that where chiral carbanions possessing this type of resonance are generated, retention, inversion, or racemization can result, depending on the solvent (see Sec. 12.A.ii). This result is explained by unsymmetrical solvation of planar or near-planar carbanions. However, some carbanions that are stabilized by adjacent sulfur or phosphorus, for example, are inherently chiral, since retention of configuration is observed where

they are generated, even in solvents that cause racemization or inversion with other carbanions.¹⁴⁵ It is known that in THF, PhCH(Li)Me behaves as a prochiral entity,¹⁴⁶ and 33 has been prepared as an optically pure α-alkoxylithium reagent.¹⁴⁷ Cyclohexyllithium (34) shows some configurational stability, and it is known that isomerization is slowed by an increase in the strength of lithium coordination and by an increase in solvent polarity.¹⁴⁸ It is known that a vinyl anion is configurationally stable whereas a vinyl radical is not. This is due to the instability of the radical anion that must be an intermediate for conversion of one isomer of vinyllithium to the other.¹⁴⁹ The configuration about the carbanionic carbon, at least for some of the α-sulfonyl carbanions, seems to be planar,¹⁵⁰ and the inherent chirality is caused by lack of rotation about the C–S bond.¹⁵¹

5.B.ii. The Structure of Organometallic Compounds¹⁵²

Whether a carbon–metal bond is ionic or polar-covalent is determined chiefly by the electronegativity of the metal and the structure of the organic part of the molecule. Ionic bonds become more likely as the negative charge on the metal-bearing carbon is decreased by resonance or field effects. Thus the sodium salt of acetoacetic ester has a more ionic carbon–sodium bond than methylsodium.

Most organometallic bonds are polar-covalent. Only the alkali metals have electronegativities low enough to form ionic bonds with carbon, and even here the behavior of lithium alkyls shows considerable covalent character. The simple alkyls and aryls of Na, K, Rb, and Cs¹⁵³ are nonvolatile solids¹⁵⁴ insoluble in benzene or other organic solvents, while alkyllithium reagents are soluble, although they too are generally nonvolatile solids. Organolithium reagents with alkyl units (alkyllithium reagents) do not exist as monomeric species in hydrocarbon solvents or ether.¹⁵⁵ In benzene and cyclohexane, freezing-point-depression studies have shown that alkyllithium reagents are normally hexameric unless steric interactions favor tetrameric aggregates.¹⁵⁶ Nuclear magnetic resonance studies, especially measurements of ¹³C–⁶Li coupling, have also shown aggregation in hydrocarbon solvents.¹⁵⁷ Boiling-point-elevation studies have been performed in ether solutions, where alkyllithium reagents exist in two- to fivefold aggregates.¹⁵⁸ Even in the gas phase¹⁵⁹ and in the solid state,¹⁶⁰ alkyllithium reagents exist as aggregates. X-ray crystallography has shown that methyllithium has the same tetrahedral structure in the solid state as in ether solution.¹⁶⁰ However, tert-butyllithium is monomeric in THF, although dimeric in ether and tetrameric in hydrocarbon solvents.¹⁶¹ Neopentyllithium exists as a mixture of monomers and dimers in THF.¹⁶²

The C–Mg bond in Grignard reagents is covalent and not ionic. The actual structure of Grignard reagents in solution has been a matter of much controversy over the years.¹⁶³ In 1929, it was discovered¹⁶⁴ that the addition of dioxane to an ethereal Grignard solution precipitates all the magnesium halide and leaves a solution of R₂Mg in ether; (i.e., there can be no RMgX in the solution since there is no halide). The following equilibrium, now called the Schlenk equilibrium, was proposed as the composition of the Grignard solution:

in which 35 is a complex. Much work has demonstrated that the Schlenk equilibrium actually exists and that the position of the equilibrium depends on the identity of R, X, the solvent, the concentration, and the temperature.¹⁶⁵ It has been known for many years that the magnesium in a solution of a Grignard reagent, no matter whether it is RMgX, R₂Mg, or MgX₂, can coordinate with two molecules of ether in addition to the two covalent bonds to generate the solvent-coordinated species shown.

Rundle and Guggenberger¹⁶⁶ performed X-ray diffraction studies on solid phenylmagnesium bromide dietherate and on ethylmagnesium bromide dietherate, which they obtained by cooling ordinary ethereal Grignard solutions until the solids crystallized. They found that the structures were magnesium bromides (e.g., 36). These solids still contained ether. When ordinary ethereal Grignard solutions¹⁶⁷ prepared from bromomethane, chloromethane, bromoethane, and chloroethane were evaporated at ~100 °C under vacuum so that the solid remaining contained no ether, X-ray diffraction showed no RMgX, but a mixture of R₂Mg and MgX₂.¹⁶⁸ These results indicate that in the presence of ether, RMgX√2Et₂O is the preferred structure, while the loss of ether drives the Schlenk equilibrium to R₂Mg + MgX₂. However, conclusions drawn from a study of the solid materials do not necessarily apply to the structures in solution.

Boiling-point-elevation and freezing-point-depression measurements have demonstrated that in THF at all concentrations and in ether at low concentrations (up to ~0.1 M) Grignard reagents prepared from alkyl bromides and iodides are monomeric, (i.e., there are few or no molecules with two Mg atoms).¹⁶⁹ Thus, part of the Schlenk equilibrium is operating but not the other part (i.e., 35 is not present in measurable amounts). This was substantiated by NMR spectra of the ethyl Grignard reagent in THF, which showed the presence of three peaks, corresponding to EtMgBr, Et₂Mg, and MgBr₂.¹⁷⁰ That the equilibrium between RMgX and R₂Mg lies far to the left for “ethylmagnesium bromide” in ether was shown by Smith and Becker,¹⁷¹ who mixed 0.1 M ethereal solutions of Et₂Mg and MgBr₂ and found that a reaction occurred with a heat evolution of 3.6 kcal mol⁻¹ (15 kJ mol⁻¹) of Et₂Mg, and that the product was monomeric (by boiling-point elevation measurements). When either solution was added little by little to the other, there was a linear output of heat until almost a 1 : 1 molar ratio was reached. Addition of an excess of either reagent gave no further heat output. These results show that at least under some conditions the Grignard reagent is largely RMgX (coordinated with solvent), but that the equilibrium can be driven to R₂Mg by evaporation of all the ether or by addition of dioxane.

For some aryl Grignard reagents, it is possible to distinguish separate NMR chemical shifts for ArMgX and Ar₂Mg.¹⁷² From the area under the peaks, it is possible to calculate the concentrations of the two species, and from them, equilibrium constants for the Schlenk equilibrium. These data show¹⁷² that the position of the equilibrium depends very markedly on the aryl group and the solvent, but that conventional aryl Grignard reagents in ether are largely ArMgX. In THF the predominance of ArMgX is less, and with some aryl groups there is actually more Ar₂Mg present. Separate NMR chemical shifts have also been found for alkyl RMgBr and R₂Mg in HMPA¹⁷³ and in ether at low temperatures.¹⁷⁴ When Grignard reagents from alkyl bromides or chlorides are prepared in triethylamine the predominant species is RMgX.¹⁷⁵ Thus the most important factor determining the position of the Schlenk equilibrium is the solvent. For primary alkyl groups the equilibrium constant for the reaction as written above is lowest in Et₃N, higher in ether, and still higher in THF.¹⁷⁶

However, Grignard reagents prepared from alkyl bromides or iodides in ether at higher concentrations (0.5–1 M) contain dimers, trimers, and higher polymers, and those prepared from alkyl chlorides in ether at all concentrations are dimeric,¹⁷⁷ so that 35 is in solution, probably in equilibrium with RMgX and R₂Mg (i.e., the complete Schlenk equilibrium seems to be present).

The Grignard reagent prepared from 1-chloro-3,3-dimethylpentane in ether undergoes rapid inversion of configuration at the Mg containing carbon (demonstrated by NMR; this compound is not chiral).¹⁷⁸ The mechanism of this inversion is not completely known. Despite the mechanistic ambiguity, in almost all cases, it is not possible to retain the configuration of a stereogenic carbon while forming a Grignard reagent.

Organolithium reagents (RLi) are very important reagents in organic chemistry. In recent years, a great deal has been learned about their structure¹⁷⁹ in both the solid state and in solution. X-ray analysis of complexes of n-butyllithium with tetramethylethylenediamine (TMEDA), THF, and 1,2-dimethoxyethane (DME) shows them to be dimers and tetramers [e.g., (BuLi·DME)₄];¹⁸⁰ they are aggregates.¹⁸¹ X-ray analysis of isopropyllithium shows it to be a hexamer [(iPrLi)₆],¹⁸² and unsolvated lithium aryls are tetramers.¹⁸³ α-Ethoxyvinyllithium [CH₂=C(OEt)Li] shows a polymeric structure with tetrameric subunits.¹⁸⁴ Aminomethyl aryllithium reagents have been shown to be chelated and dimeric in solvents (e.g., THF).¹⁸⁵ There are several functionalized organolithium reagents.¹⁸⁶

The dimeric, tetrameric, and hexameric structures of organolithium reagents¹⁸⁷ in the solid state is often retained in solution, but this is dependent on the solvent and complexing additives, if any. A tetrahedral organolithium compound is known,¹⁸⁸ and the X-ray of an α,α-dilithio hydrocarbon has been reported.¹⁸⁹ Phenyllithium is a mixture of tetramers and dimers in diethyl ether, but stoichiometric addition of THF, DME, or TMEDA leads to the dimer.¹⁹⁰ The solution structures of mixed aggregates of butyllithium and amino-alkaloids has been determined¹⁹¹ as well as the solution structure of sulfur-stabilized allyllithium compounds.¹⁹² Vinyllithium is an 8:1 mixture of tetramer/dimer in THF at −90 °C, but addition of TMEDA changes the ratio of tetramer/dimer to 1 : 13 at −80 °C.¹⁹³ Internally solvated allylic lithium compounds have been studied, showing the coordinated lithium to be closer to one of the terminal allyl carbons.¹⁹⁴ A relative scale of organolithium stability has been established,¹⁹⁵ and the issue of configurational stability of enantioenriched organolithium reagents has been examined.¹⁹⁶

Enolate anions are an important class of carbanions that appear in a variety of important reactions, including alkylation α to a carbonyl group and the aldol (16-34) and Claisen condensation (16-85) reactions. Metal enolate anions of aldehydes, ketones, esters, and other acid derivatives exist as aggregates in ether solvents.¹⁹⁷ There is evidence that the lithium enolate of isobutyrophenone is a tetramer in THF,¹⁹⁸ but a dimer in DME.¹⁹⁹ X-ray crystallography of ketone enolate anions have shown that they can exist as tetramers and hexamers.²⁰⁰ There is also evidence that the aggregate structure is preserved in solution and is probably the actual reactive species. Lithium enolate anions derived from esters are as dimers in the solid state²⁰¹ that contain four THF molecules. It has also been established that the reactivity of enolate anions in alkylation and condensation reactions is influenced by the aggregate state of the enolate. It is also true that the relative proportions of (E) and (Z) enolate anions are influenced by the extent of solvation and the aggregation state. Addition of LiBr to a lithium enolate anion in THF suppresses the concentration of monomeric enolate.²⁰²Ab initio studies confirm the aggregate state of acetaldehyde.²⁰³ It is also known that α-Li benzonitrile [PhCH(Li)CN] exists as a dimer in ether and with TMEDA.²⁰⁴ Mixed aggregates of tert-butyllithium and lithium tert-butoxide are known to be hexameric.²⁰⁵

It might be mentioned that matters are much simpler for organometallic compounds with less-polar bonds. Thus Et₂Hg and EtHgCl are both definite compounds, the former is a liquid and the latter is a solid. Organocalcium reagents are also known, and are formed from alkyl halides via a single electron transfer (SET) mechanism with free radical intermediates.²⁰⁶

5.B.iii. The Generation and Fate of Carbanions

There are two principal ways in which most carbanions are generated.

1. A Group Attached to a Carbon Leaves Without Its Electron Pair

The “leaving group” is most often a proton. In fact, the proton is removed by a suitable base, and this is a simple acid–base reaction.²⁰⁷ However, other leaving groups are known (see Chap 12), such as carboxyl:

2. A Negative Ion Adds to a Carbon–Carbon Double or Triple Bond (see Chapter 15)

The addition of a negative ion to a carbon–oxygen double bond (C=O) does not give a carbanion, but an alkoxide (R–O⁻), since the negative charge resides on the oxygen.

The most common reaction of carbanions is to donate electrons to a positive species, often a proton, or with another species that has an empty orbital in its outer shell (a Lewis acid–base reaction):

This means that carbanions react with electrophilic atoms (those functionalized so there is a δ⁺ carbon atom); see Chapter 16.

Carbanions may also form a bond with a carbon that already has four bonds, by displacing one of the four groups (S_N2 reaction, see Chapter 10):

Like carbocations, carbanions can also react in ways in which they are converted to species that are still charged. They can add to double bonds (usually C=O double bonds; see Chapters 10 and 16),

or rearrange, although this is rare (see Chapter 18),

or they are oxidized to free radicals.²⁰⁸ A system in which a carbocation [Ph(p-Me₂NC₆H₄)₂C⁺] oxidizes a carbanion [(p-NO₂C₆H₄)₃C⁻] to give two free radicals, reversibly, so that all four species are present in equilibrium, has been demonstrated.^209,210

Organometallic compounds that are not ionic but polar–covalent behave very much as if they were ionic and give similar reactions.

5.C. Free Radicals

5.C.i. Stability and Structure211

A free radical (usually just called a radical) may be defined as a species that contains one or more unpaired electrons. Note that this definition includes certain stable inorganic molecules (e.g., NO and NO₂), as well as many individual atoms (e.g., Na and Cl). As with carbocations and carbanions, simple alkyl radicals are very reactive and are usually transient species. For the most part, their lifetimes are extremely short in solution, but they can be kept frozen for relatively long periods of time within the crystal lattices of other molecules.²¹² There are, however, many stable radicals,²¹³ some of which will be noted below. Many spectral²¹⁴ measurements have been made on radicals trapped in this manner. Even under these conditions the methyl radical decomposes with a half-life of 10–15 min in a methanol lattice at 77 K.²¹⁵ Since the lifetime of a radical depends not only on its inherent stability, but also on the conditions under which it is generated, the terms persistent and stable are usually used for the different senses. A stable radical is inherently stable; a persistent radical has a relatively long lifetime under the conditions at which it is generated, although it may not be very stable.

Radicals can be characterized by several techniques (e.g., mass spectrometry²¹⁶ or the characterization of alkoxycarbonyl radicals by Step–Scan Time-Resolved Infrared Spectroscopy).²¹⁷ Another technique makes use of the magnetic moment that is associated with the spin of an electron, which can be expressed by a quantum number of or . According to the Pauli principle, any two electrons occupying the same orbital must have opposite spins, so the total magnetic moment is zero for any species in which all the electrons are paired. In radicals, however, one or more electrons are unpaired, so there is a net magnetic moment and the species is paramagnetic. Radicals can therefore be detected by magnetic-susceptibility measurements, but for this technique a relatively high concentration of radicals is required.

A much more important technique is electron spin resonance (ESR), also called electron paramagnetic resonance (EPR).²¹⁸ The principle of ESR is similar to that of NMR, except that electron spin is involved rather than nuclear spin. The two electron spin states ( and ) are ordinarily of equal energy, but in a magnetic field the energies are different. As in NMR, a strong external field is applied and electrons are caused to flip from the lower state to the higher by the application of an appropriate radio frequency signal. Inasmuch as two electrons paired in one orbital must have opposite spins that cancel, an ESR spectrum arises only from species that have one or more unpaired electrons (i.e., free radicals).

Since only free radicals give an ESR spectrum, the method can be used to detect the presence of radicals and to determine their concentration.²¹⁹ Furthermore, information concerning the electron distribution (and hence the structure) of free radicals can be obtained from the splitting pattern of the ESR spectrum (ESR peaks are split by nearby protons).²²⁰ Fortunately (for the existence of most free radicals is very short), it is not necessary for a radical to be persistent for an ESR spectrum to be obtained. Electron spin resonance spectra have been observed for radicals with lifetimes considerably <1 s. Failure to observe an ESR spectrum does not prove that radicals are not involved, since the concentration may be too low for direct observation. In such cases, the spin-trapping technique can be used.²²¹ In this technique, a compound is added that is able to combine with very reactive radicals to produce more persistent radicals; the new radicals can be observed by ESR. Azulenyl nitrones have been developed as chromotropic spin-trapping agents.²²² An important class of spin-trapping compounds are nitroso compounds, which react with radicals to give stable nitroxide radicals:²²³ RN=O + R′√ → RR′N–O√. An N-oxide spin trap has been developed [37; 2(diethylphosphino)-5,5-dimethyl-1-pyrroline-N-oxide], and upon trapping a reactive free radical, ³¹P NMR can be used to identify it.²²⁴ This technique is effective, and short-lived species (e.g., the oxiranylmethyl radical) have been detected by spin trapping.²²⁵ Other molecules have been used to probe the intermediacy of radicals via SET processes. They are called SET probes.²²⁶

Because there is an equal probability that a given unpaired electron will have a quantum number of or , radicals are observed as a single line in an ESR spectrum unless they interact with other electronic or nuclear spins or possess magnetic anisotropy, in which case two or more lines may appear in the spectrum.²²⁷

Another magnetic technique for the detection of free radicals uses an ordinary NMR instrument. It was discovered²²⁸ that if an NMR spectrum is taken during the course of a reaction, certain signals might be enhanced, either in a positive or negative direction; others may be reduced. When this type of behavior, called chemically induced dynamic nuclear polarization²²⁹ (CIDNP), is found in the NMR spectrum of the product of a reaction, it means that at least a portion of that product was formed via the intermediacy of a free radical.²³⁰ For example, the question was raised whether radicals were intermediates in the exchange reaction between ethyl iodide and ethyllithium (Reaction 12-39):

Curve a in Fig. 5.1²³¹ shows an NMR spectrum taken during the course of the reaction. Curve b is a reference spectrum of ethyl iodide (CH₃ protons at δ = 1.85; CH₂ protons at δ = 3.2). Note that in curve a some of the ethyl iodide signals are enhanced; others go below the base line (negative enhancement; also called emission). Thus the ethyl iodide formed in the exchange shows CIDNP and so was formed via a free radical intermediate. Chemically induced dynamic nuclear polarization results when protons in a reacting molecule become dynamically coupled to an unpaired electron while traversing the path from reactants to products. Although the presence of CIDNP almost always means that a free radical is involved,²³² its absence does not prove that a free radical intermediate is necessarily absent, since reactions involving free radical intermediates can also take place without observable CIDNP. Also, the presence of CIDNP does not prove that all of a product was formed via a free radical intermediate, only that some of it was. Note that dynamic nuclear polarization (DNP) enhances signal intensities in the NMR spectra of solids and liquids. In a contemporary DNP experiment, a diamagnetic sample is doped with a paramagnet and the large polarization of the electron spins is transferred to the nuclei via microwave irradiation of the EPR spectrum.²³³ Dynamic nuclear polarization has been used to examine biradicals.²³⁴

Fig. 5.1²³¹ (a) The NMR spectrum taken during reaction between EtI and EtLi in benzene (the region between 0.5 and 3.5 δ was scanned with an amplitude twice that of the remainder of the spectrum). The signals at 1.0–1.6 δ are due to butane, some of which is also formed in the reaction. (b) Reference spectrum of EtI. [Reprinted with permission from Ward, H.R.; Lawler, R.G.; Cooper, R.A. J. Am. Chem. Soc. 1969, 91, 746. Copyright © 1969 American Chemical Society.]

As with carbocations, the stability order of free radicals is tertiary > secondary > primary, explainable by field effects and hyperconjugation, analogous to that in carbocations (Sec. 5.A.ii).²³⁵

With resonance possibilities, the stability of free radicals increases;²³⁶ some can be kept indefinitely.²³⁷ Benzylic and allylic²³⁸ radicals for which canonical forms can be drawn similar to those shown for the corresponding cations (Sec. 5.A.ii) and anions (Sec. 5.B.i, category 1) are more stable than simple alkyl radicals, but still have only a transient existence under ordinary conditions. Note that 2-phenylethyl radicals have been shown to exhibit bridging of the phenyl group.²³⁹

The triphenylmethyl and similar radicals²⁴⁰ are stable enough to exist in solution at room temperature, although they are in equilibrium with a dimeric form. The concentration of triphenylmethyl radical in benzene solution is ~2% at room temperature. For many years, it was assumed that Ph₃C√, the first stable free radical known,²⁴¹ dimerized to hexaphenylethane (Ph₃C–CPh₃),²⁴² but UV and NMR investigations have shown that the true structure is 38.²⁴³ Although triphenylmethyl-type radicals are stabilized by resonance:

steric hindrance to dimerization and not resonance is the major cause of their stability.²⁴⁴ This was demonstrated by the preparation of the radicals 39 and 40.²⁴⁵ These radicals are electronically very similar, but 39, being planar, has much less steric hindrance to dimerization than Ph₃C√, while 40, with six groups in ortho positions, has much more. On the other hand, the planarity of 35 means that it has a maximum amount of

resonance stabilization, while 40 must have much less, since its degree of planarity should be even less than Ph₃C√, which itself is propeller shaped and not planar. Thus if resonance is the chief cause of the stability of Ph₃C√, 40 should dimerize and 39 should not, but if steric hindrance is the major cause, the reverse should happen. It was found²³³ that 40 gave no evidence of dimerization, even in the solid state, while 39 existed primarily in the dimeric form, which is dissociated to only a small extent in solution.²⁴⁶ This result indicates that steric hindrance to dimerization is the major cause for the stability of triarylmethyl radicals. A similar conclusion was reached in the case of (NC)₃C√, which dimerizes readily although it is considerably stabilized by resonance.²⁴⁷ Nevertheless, that resonance is still an important contributing factor to the stability of radicals is shown by the facts that (1) the radical t-Bu(Ph)₂C√ dimerizes more than Ph₃C√, while p-PhCOC₆H₄(Ph₂)C√ dimerizes less.²⁴⁸ The latter has more canonical forms than Ph₃C√, but steric hindrance should be about the same (for attack at one of the two rings). (2) A number of radicals (p-XC₆H₄)₃C√, with X = F, Cl, O₂N, CN, and so on, do not dimerize, but are kinetically stable.²⁴⁹ Completely chlorinated triarylmethyl radicals are more stable than the unsubstituted kind, probably for steric reasons, and many are quite inert in solution and in the solid state.²⁵⁰

Allylic radical are relatively stable, and the pentadienyl radical is particularly stable, but (E,E)-, (E,Z)-, and (Z,Z)-stereoisomers can form. It has been calculated that the (Z,Z)-pentadienyl radical is 5.6 kcal mol⁻¹ less stable than the (E,E)-pentadienyl radical.²⁵¹ Note that vinyl radicals have (E)- and (Z)-forms and the inversion barrier from one to the other increases as the electronegativity of substituents increase.²⁵² Conjugated propargylic radicals are calculated to have diminished stability as the conjugation increases, in contrast to the behavior of alkenes.²⁵³ Cyclopropyl alkynes have been used as mechanistic probes to distinguish between vinyl radicals and ionic intermediates.²⁵⁴ Enolate radicals are also known.²⁵⁵

It has been postulated that the stability of free radicals is enhanced by the presence at the radical center of both an electron-donating and an electron-withdrawing group.²⁵⁶ This finding is called the push–pull or captodative effect (see also, Sec. 4.K.i). The effect arises from increased resonance, as in 41.

There is some evidence in favor²⁵⁷ of the captodative effect, some of it from ESR studies.²⁵⁸ However, there is also experimental²⁵⁹ and theoretical²⁶⁰ evidence against it. There is evidence that while FCH₂√ and F₂CH√ are more stable than CH₃√, the radical CF₃√ is less stable; that is, the presence of the third F destabilizes the radical.²⁶¹

Certain radicals with unpaired electron on a carbon are also very stable.²⁶² Radicals can be stabilized by intramolecular hydrogen bonding.²⁶³ Diphenylpicrylhydrazyl (42) is a solid that can be kept for years, and stable neutral azine radicals have been prepared.²⁶⁴ Nitroxide radicals were mentioned previously,²⁶⁵ and the commercially available TEMPO (2,2,6,6-tetramethylpiperidine-1-oxyl) free radical (43) is a stable nitroxyl radical used in chemical reactions (e.g., oxidations),²⁶⁶ or as a spin trap.²⁶⁷ Nitroxyl radical 44 is a nitroxide radical so stable that reactions can be performed on it (e.g., the Grignard reaction shown with 44; see Reaction 16-24) without affecting the unpaired electron²⁶⁸ (the same is true for some of the chlorinated triarylmethyl radicals mentioned above²⁶⁹). Several nitrogen-containing groups are known to stabilize radicals, and the most effective radical stabilization is via spin delocalization.²⁷⁰ A number of persistent N-tert-butoxy-1-aminopyrenyl radicals (e.g., 45) have been isolated as monomeric radical crystals (see 46, the X-ray crystal

structure of 45),²⁷¹ and monomeric N-alkoxyarylaminyls have been isolated.²⁷² α-Trichloromethylbenzyl(tert-butyl)aminoxyl (47) is extremely stable.²⁷³ In aqueous media it is stable for > 30 days, and in solution in an aromatic hydrocarbon solvent it has survived for >90 days.²⁷³ Although the stable nitroxide radicals have the α-carbon blocked to prevent radical formation there, stable nitroxide radicals are also known with hydrogen at the α-carbon,²⁷⁴ and long-lived vinyl nitroxide radicals are known.²⁷⁵ A stable organic radical lacking resonance stabilization has been prepared (48), and its X-ray crystal structure was obtained.²⁷⁶ Dissociation energies (D values) of R–H bonds provide a measure of the relative inherent stability of free radicals R.²⁷⁷ Table 5.4 lists such values. ^278279280281 The higher the D value, the less stable the radical. Bond-dissociation energies also have been reported for the C–H bond of alkenes and dienes²⁸² and for the C–H bond in radical precursors XYC–H, where X,Y can be H, alkyl, COOR, COR, SR, CN, NO₂, and so on.²⁸³ Bond dissociation energies for the C–O bond in hydroperoxide radicals (ROO√) have also been reported.²⁸⁴ However, note that basing radical stabilization energy on the difference between the bond dissociation energy (BDE) of CH₃–H, as a reference point, and of R–H has been observed to have shortcomings.²⁸⁵ The problem is that these values are only applicable to carbon-centered radicals, and the stabilization energies are not transferable and cannot be used to estimate BDE of R–R′, R–R, or any R–X compounds.²⁸²

Table 5.4 The D₂₉₈ Values for Some R–H Bonds^a,b

There are two possible structures for simple alkyl radicals.²⁸⁶ They might have sp² bonding, in which case the structure would be planar, with the odd electron in a p orbital, or the bonding might be sp³, which would make the structure pyramidal and place the odd electron in an sp³ orbital. The ESR spectra of √CH₃ and other simple alkyl radicals as well as other evidence indicate that these radicals have planar structures.²⁸⁷ This finding is in accord with the known loss of optical activity when a free radical is generated at a stereogenic carbon.²⁸⁸ In addition, electronic spectra of the CH₃ and CD₃ radicals (generated by flash photolysis) in the gas phase have definitely established that under these conditions the radicals are planar or near planar.²⁸⁹ The IR spectra of √CH₃ trapped in solid argon led to a similar conclusion.²⁹⁰ Despite the usual loss of optical activity noted above, asymmetric radicals can be prepared in some cases. For example, asymmetric nitroxide radicals are known.²⁹¹ An anomeric effect was observed in alkoxy radical 49, where the ratio of 49a/49b was 1:1.78.²⁹²

Evidence from studies on bridgehead compounds shows that although a planar configuration is more stable, pyramidal structures are not impossible. In contrast to the situation with carbocations, free radicals have often been generated at bridgeheads, although studies have shown that bridgehead free radicals are less rapidly formed than the corresponding open-chain radicals.²⁹³ In sum, the available evidence indicates that although simple alkyl free radicals prefer a planar, or near-planar shape, the energy difference between a planar and a pyramidal free radical is not great. However, free radicals in which the carbon is connected to atoms of high electronegativity (e.g., √CF₃), prefer a pyramidal shape;²⁹⁴ increasing the electronegativity increases the deviation from planarity.²⁹⁵ Cyclopropyl radicals are also pyramidal.²⁹⁶ Free radicals with resonance are definitely planar, although triphenylmethyl-type radicals are propeller shaped,²⁹⁷ like the analogous carbocations (Sec. 5.A.i). Radicals possessing simple alkyl substituents attached to the radical carbon (C√) that have C^sp3–C^sp3 bonds, and rotation about those bonds is possible. The internal rotation barrier for the tert-butyl radical (Me₃C√), for example, was estimated to be ~1.4 kcal mol⁻¹ 6 kJ mol⁻¹.²⁹⁸

A number of diradicals (also called biradicals) are known,²⁹⁹ and the thermodynamic stability of diradicals has been examined.³⁰⁰ Orbital phase theory has been applied to the development of a theoretical model of localized 1,3-diradicals, and used to predict the substitution effects on the spin preference and S–T gaps, and to design stable localized carbon-centered 1,3-diradicals.³⁰¹ When the unpaired electrons of a diradical are widely separated, for example, as in √CH₂CH₂CH₂CH₂√, the species behaves spectrally like two doublets. When they are close enough for interaction or can interact through an unsaturated system (as in trimethylenemethane),³⁰² they can have total spin numbers of +1, 0, or -1, since each electron could be either or . Spectroscopically they are called triplets,³⁰³ since each of the three possibilities is represented among the molecules and gives rise to its own spectral peak. In triplet molecules, the two unpaired electrons have the same spin. Not all diradicals have a triplet ground state. In 2,3-dimethylelecycohexane-1,4-diyl (50), the singlet and triplet states were found to be almost degenerate.³⁰⁴ Diradicals (e.g., 51) are very stable with a triplet ground state.³⁰⁵ Diradicals are generally short-lived species. The lifetime of 52 was measured to be <0.1 ns and other diradicals were found to have lifetimes in the 4–316-ns range.³⁰⁶ Diradical 53 [3,5-di-tert-butyl-3′-(N-tert-butyl-N-aminoxy)-4-oxybiphenyl] was found to have a lifetime of weeks even in the presence of oxygen, and survived brief heating in toluene up to ~60 °C.³⁰⁷ Radicals with both unpaired electrons on the same carbon are discussed under carbenes. 1,4-Biradicals are known, and α-carbonyl substituents increase the lifetime of the radical, and negative α-hyperconjugation (see Sec. 2.M) has been suggested as the cause.³⁰⁸

5.C.ii. The Generation and Fate of Free Radicals³⁰⁹

Free radicals are formed from molecules by breaking a bond so that each fragment keeps one electron.^310,311 The energy necessary to break the bond is supplied in one of two ways.

1. Thermal Cleavage. Subjection of any organic molecule to a high enough temperature in the gas phase results in the formation of free radicals. When the molecule contains bonds with D values or 20–40 kcal mol⁻¹ (80–170 kJ mol⁻¹), cleavage can be caused in the liquid phase. Two common examples are cleavage of diacyl peroxides to acyl radicals that decompose to alkyl radicals³¹² and cleavage of azo compounds to alkyl radicals³¹³

2. Photochemical Cleavage (see Sec. 7.A.v). Light energy of 600–300 nm is 48–96 kcal mol⁻¹ (200–400 kJ mol⁻¹), which is on the order of magnitude of covalent-bond energies. Typical examples are photochemical cleavage of alkyl halides in the presence of triethylamine,³¹⁴ alcohols in the presence of mercuric oxide and iodine,³¹⁵ alkyl 4-nitrobenzenesulfenates,³¹⁶ chlorine and of ketones:

Photolytic decomposition of N-hydroxypyridin-2-thione is a method that generates hydroxyl radicals.³¹⁷ The photochemistry of radicals and biradicals has been reviewed.³¹⁸

Radicals are also formed from other radicals, either by the reaction between a radical and a molecule (which must give another radical, since the total number of electrons is odd) or by cleavage of a radical³¹⁹ to give another radical, for example, the decomposition of benzoyl peroxide to give the benzoyl radical:

Radicals can also be formed by oxidation or reduction, including electrolytic methods.

Reactions of free radicals either give nonradical products (termination reactions) or lead to other radicals, which themselves must usually react further (propagation reactions). The most common termination reactions are simple coupling of similar or different radicals:

Another termination process is disproportionation:³²⁰

A propagation reaction is one in which a radical reacts to give at least one radical product, which continues the radical reaction sequence. There are four principal propagation reactions, of which the first two are most common:

1. Abstraction of Another Atom or Group, Usually a Hydrogen Atom (also see Chap 14).

A radical may abstract hydrogen atoms from a second molecule, or by an intramolecular process. A bromine radical (Br√) reacts with an alkane, for example, to give HBr and a carbon radical. This type of reaction is known as hydrogen-atom transfer. Water is an excellent hydrogen atom source for many reactions involving metals.³²¹ The reduction of a carbon radical with Bu₃SnH is an example of a hydrogen-transfer reaction (see Sec. 14.A.i). Indeed, carbon radicals react as hydrogen-bond acceptors.³²² Other atoms may be removed by a radical via atom-transfer reactions. A halogen atom can be transferred in some cases, including the transfer of an iodine atom from an aryl iodide to give an aryl radical.³²³ Solvent effects play a role in hydrogen-atom transfer (hydrogen abstraction), and hydrogen-bonding plays a role.³²⁴

2. Addition to a Multiple Bond (see Chap 15).

The radical formed from an alkene may add to the double bond of a second equivalent of alkene, and so on. This is one of the chief mechanisms for vinyl polymerization.

3. Decomposition. This process can be illustrated by the decomposition of the benzoxy radical (see 55).

4. Rearrangement.

This reaction is less common than rearrangement of carbocations, but it does occur (though not when R = alkyl or hydrogen; see Chapter 18). Perhaps the best-known rearrangement is that of cyclopropylcarbinyl radicals to a butenyl radical.³²⁵ The rate constant for this rapid ring opening has been measured in certain functionalized cyclopropylcarbinyl radicals by picosecond radical kinetics.³²⁶ Substituent effects on the kinetics of ring opening in substituted cyclopropylcarbinyl radicals have been studied.³²⁷ “The cyclopropylcarbinyl radical (56) has found an important application as a radical clock.³²⁸ Various radical processes can be clocked by the competition of direct reaction with the cyclopropylcarbinyl radical (k_t) and opening of that radical to the 1-buten-4-yl radical (k_r) followed by trapping. Relative rates (k_t/k_r) can be determined from yields of 4-X-1-butene and cyclopropylcarbinyl products as a function of the radical trap³²⁹ (X–Y) concentration. Absolute rate constants have been determined for a number of radicals with various radical traps by laser flash photolysis methods.³³⁰ From these absolute rate constants, reasonably accurate values of k_t can be estimated, and with the relative rate (k_t/k_r), a value for k_r can be calculated. From the calibrated radical-clock reaction rate (k_r), rates (k_t) of other competing reactions can be determined from relative rate data (k_t/k_r).”³²⁶ Other radical clocks are known.³³¹

Free radicals can also be oxidized to carbocations or reduced to carbanions.³³²

5.C.iii. Radical Ions³³³

Several types of radical anions are known with the unpaired electron or the charge or both on atoms other than carbon. Examples include semiquinones³³⁴ (57), acepentalenes (58),³³⁵ ketyls³³⁶ (59) and the radical anion of the isolable dialkylsilylene (60).³³⁷ Radical anions are formed by the reaction of carbene anions with chloromethanes.³³⁸ Reactions in which alkali metals are reducing agents often involve radical anion intermediates (Birch reduction, e.g., Reaction 15-13) that proceed via radical anion 61.

Several types of radical cation are also known.³³⁹ Typical examples include alkyl azulene cation radicals (62),³⁴⁰ trialkyl amine radical cations,³⁴¹ 1,2-bis(dialkylamino)benzenes radical cations (e.g., 63),³⁴² dimethylsulfonium cation radicals (Me₂S√⁺),³⁴³N-alkyl substituted imine cation radicals (Ph₂C=NEt√⁺),³⁴⁴ dibenzo[a,e]cyclooctene (64, a nonplanar cation radical),³⁴⁵ and [n.n]paracyclophane cation radicals.³⁴⁶ A twisted radical cation derived from bicyclo[2.2.2]oct-2-ene has been reported.³⁴⁷

5.D. Carbenes

5.D.i. Stability and Structure348

Carbenes are highly reactive species, and practically all have lifetimes considerably < 1 s. With exceptions noted below (Sec. 5.D.ii), carbenes have been isolated only by entrapment in matrices at low temperatures (77 K or less).³⁴⁹ The parent species (CH₂) is usually called methylene, although derivatives are more often named by the carbene nomenclature. Thus CCl₂ is generally known as dichlorocarbene, although it can also be called dichloromethylene.

The two nonbonded electrons of a carbene can be either paired or unpaired. If they are paired, the species is spectrally a singlet, while, as seen above (Sec. 5.C.i), two unpaired electrons appear as a triplet. An ingenious

method of distinguishing between the two possibilities was developed by Skell,³⁵⁰ based on the common reaction of addition of carbenes to double bonds to form cyclopropane derivatives (Reaction 15-51). If the singlet species adds to cis-2-butene, the resulting cyclopropane should be the cis isomer since the movements of the two pairs of electrons

should occur either simultaneously or with one rapidly succeeding another. However, if the attack is by a triplet species, the two unpaired electrons cannot both go into a new covalent bond, since by Hund's rule they have parallel spins. So one of the unpaired electrons will form a bond with the electron from the double bond that has the opposite spin, leaving two unpaired electrons that have the same spin and therefore cannot form a bond at once, but must wait until, by some collision process, one of the electrons can reverse its spin. During this time, there is free rotation about the C–C bond and a mixture of cis- and trans-1,2-dimethylcyclopropanes should result.³⁵¹

The results of this type of experiment show that CH₂ itself is usually formed as a singlet species, which can decay to the triplet state, which consequently has a lower energy (MO calculations³⁵² and experimental determinations show that the difference in energy between singlet and triplet CH₂ is ~8–10 kcal mol⁻¹ or 33–42 kJ mol⁻¹)³⁵³. However, it is possible to prepare triplet CH₂ directly by a photosensitized decomposition of diazomethane.³⁵⁴ The CH₂ group is so reactive³⁵⁵ that it generally reacts as the singlet before it has a chance to decay to the triplet state.³⁵⁶ As to other carbenes, some react as triplets, some as singlets, and others as singlets or triplets, depending on how they are generated. There are, however, molecules that generate persistent triplet carbenes.³⁵⁷ Indeed, remarkably stable diaryl triplet carbenes have been prepared,³⁵⁸ and protected diphenylcarbenes are particularly stable.³⁵⁹ There are also persistent singlet carbenes, although radical fragmentation is a problem.³⁶⁰

There is a limitation to the use of stereospecificity of addition as a diagnostic test for singlet or triplet carbenes.³⁶¹ When carbenes are generated by photolytic methods, they are often in a highly excited singlet state. When they add to the double bond, the addition is stereospecific; but the cyclopropane formed carries excess energy (i.e., it is in an excited state). It has been shown that under certain conditions (low pressures in the gas phase) the excited cyclopropane may undergo cis–trans isomerization after it is formed, so that triplet carbene may seem to be involved although in reality the singlet was present.³⁶²

Studies of the IR spectrum of CCl₂ trapped at low temperatures in solid argon indicate that the ground state for this species is the singlet.³⁶³ The geometrical structure of triplet methylene can be investigated by ESR measurements,³⁶⁴ since triplet species are diradicals. Such measurements made on triplet CH₂ trapped in matrices at very low temperatures (4 K) show that triplet CH₂ is a bent molecule, with an angle of ~136°.³⁶⁵ The EPR measurements cannot be made on singlet species, but from electronic spectra of CH₂ formed in flash photolysis³⁶⁶ of diazomethane it was concluded that singlet CH₂ is also bent, with an angle of ~103°.³⁶⁷ Singlet CCl₂³⁰⁰ and CBr₂³⁶⁸ are also bent, with angles of 100 and 114°, respectively. It has long been known that triplet aryl carbenes are bent.³⁶⁹

The most common carbenes are :CH₂ and :CCl₂,³⁷⁰ but many others have been reported,³⁷¹ including heterocyclic carbenes³⁷² diboron carbenes,³⁷³ 65 (stabilized by the steric constraints of the ring geometry),³⁷⁴ 66 (an aminocarbene without π conjugation),³⁷⁵ bicyclo[2.2.2]octylidene, (67),³⁷⁶ alkylidene carbenes (e.g., 68),³⁷⁷ conformationally restricted cyclopropylcarbenes, (e.g., 69),³⁷⁸ β-silylcarbenes (e.g., 70),³⁷⁹ α-keto carbenes,³⁸⁰ vinyl carbenes,³⁸¹ and chiral carbenoids.³⁸² Fluoro(phenoxy)carbene is stable for several days if it is generated within the cavity of a hemicarcerand (see Sec. 3.C.iii).³⁸³ In the case of 65 (R = Ph),³⁸⁴ the precursor is a tetraaminoethylene, and when potassium hydride is present to preclude electrophilic catalysis, starting tetraaminoethylenes are recovered unchanged.

Flash photolysis of CHBr₃ produced the intermediate CBr,³⁸⁵ which is a carbyne.

The intermediates CF and CCl were generated similarly from CHFBr₂ and CHClBr₂, respectively. Triplet acetylenes have been reported as equivalents for 1,2-bicarbenes.³⁸⁶

5.D.ii. The Generation and Fate of Carbenes³⁸⁷

There are two primary methods to form carbenes, although other pathways are also known.

1. In α elimination, a carbon loses a group without its electron pair, usually a proton, and then a group with its pair, usually a halide ion:³⁸⁸

The most common example is formation of dichlorocarbene by treatment of chloroform with a base (see Reaction 10-3) and geminal alkyl dihalides with Me₃Sn⁻,³⁸⁹ but many other examples are known, such as

	Ref. 390
	Ref. 391

2. Disintegration of compounds containing certain types of double bonds:

The two most important ways of forming:CH₂ are examples: the photolysis of ketene

and the isoelectronic decomposition of diazomethane.³⁹²

Some diazoalkanes decompose to the corresponding carbene.³⁹³ Diazirines³⁹⁴ (isomeric with diazoalkanes) give carbenes,³⁹⁵ but arylmethyl radicals have also been generated from diazirines.³⁹⁶ In a different study, thermolysis of diaryloxydiazirines (71) gave the anticipated carbene products, but photolysis gave both carbenes and aryloxy radicals by α-scission.³⁹⁷

Because most carbenes are so reactive, it is often difficult to prove that they are actually present in a given reaction. The lifetime of formylcarbene was measured to be 0.15–0.73 ns by transient absorption and transient grating spectroscopy in dichloromethane.³⁹⁸ In many instances, where a carbene is apparently produced by an α elimination or by disintegration of a double-bond compound, there is evidence that no free carbene is actually involved. The neutral term carbenoid is used where it is known that a free carbene is not present or in cases where there is doubt. α-Halo organometallic compounds, (R₂CXM) are often called carbenoids because they readily give elimination reactions³⁹⁹ (e.g., see Reaction 12-39).

The reactions of carbenes are more varied than those of the species previously discussed in this chapter.⁴⁰⁰ Solvent effects have been observed in carbene reactions. The selectivity of certain carbenes is influenced by the nature of the solvent.⁴⁰¹ The distribution of rearrangement products (see below) from tert-butylcarbene⁴⁰² are influenced by changes in solvent.⁴⁰³ It is known that singlet methylene forms a charge-transfer complex with benzene.⁴⁰⁴ Solvent interactions for chlorophenylcarbene and fluorophenylcarbene, however, are weak.⁴⁰⁵

1. Additions to carbon–carbon double bonds have already been mentioned. Carbenes also add to aromatic systems, but the immediate products rearrange, usually with ring enlargement (see Reaction 15-65). Additions of carbenes to other double bonds [e.g., C=N (Reactions 16-46 and 16-48), and to triple bonds], have also been reported.

2. An unusual reaction of carbenes is that of insertion into C–H bonds (Reaction 12-21). Thus :CH₂ reacts with methane to give ethane and with propane

to give n-butane and isobutane, as shown. Elimination to give an alkene is a competing side reaction in polar solvents, but this is suppressed in nonpolar solvents.⁴⁰⁶ Simple alkyl carbenes, such as this, are not very useful for synthetic purposes, but do illustrate the extreme reactivity of carbene. However, carbenoids generated by rhodium-catalyzed decomposition of diazoalkanes are very useful (see Reaction 12-23) and have been used in a variety of syntheses. Treatment in the liquid phase of an alkane (e.g., pentane) with carbene formed from the photolysis of diazomethane, gives the three possible products in statistical ratios⁴⁰⁷ demonstrating that carbene is displaying no selectivity. For many years, it was a generally accepted principle that the lower the selectivity the greater the reactivity; however, this principle is no longer regarded as general because many exceptions have been found.⁴⁰⁸ Singlet CH₂ generated by photolysis of diazomethane is probably the most reactive organic species known, but triplet CH₂ is somewhat less reactive, and other carbenes are still less reactive. The following series of carbenes of decreasing reactivity has been proposed on the basis of discrimination between insertion and addition reactions: CH₂ > HCCOOR > PhCH > BrCH ~ ClCH.⁴⁰⁹ Dihalocarbenes generally do not give insertion reactions at all. Insertion of carbenes into other bonds has also been demonstrated, although not insertion into C–C bonds.⁴¹⁰

Two carbenes that are stable at room temperature have been reported:⁴¹¹ 72 and 73. In the absence of oxygen and moisture, 72 exists as stable crystals with a melting point of 240–241 °C.⁴¹² This structure was proved by X-ray crystallography.

3. It would seem that dimerization to form an alkene should be an important reaction of carbenes, but it is not.

Generally, the reactivity is so great that the carbene species do not have time to find each other and because the dimer generally has so much energy that it dissociates again. Apparent dimerization has been observed, but it is likely that the products in many reported instances of “dimerization” do not arise from an actual dimerization of two carbenes, but come from attack by a carbene on a molecule of a carbene precursor, for example,

4. Alkylcarbenes can undergo rearrangement, with migration of alkyl or hydrogen.⁴¹³ Indeed these rearrangements are generally so rapid⁴¹⁴ that additions to multiple bonds and insertion reactions, which are so common for CH₂, are seldom encountered with alkyl or dialkyl carbenes. Unlike rearrangement of the species previously encountered in this chapter, most rearrangements of carbenes directly give stable molecules. A carbene intermediate has been suggested for the isomerization of cyclopropane.⁴¹⁵ Some examples of carbene rearrangement are

	Ref. 416
	Ref. 417
	Ref. 418
	Ref. 419

The rearrangement of acylcarbenes to ketenes is called the Wolff rearrangement (Reaction 18-8). A few rearrangements in which carbenes rearrange to other carbenes are also known.⁴²⁰ Of course, the new carbene must stabilize itself in one of the ways mentioned.

5. The fragmentation reactions of alicyclic oxychlorocarbenes (e.g., 74 and 75)⁴²¹ give substitution and elimination products. Menthyloxychlorocarbene (74) gave primarily the substitution product, whereas neomenthyloxychlorocarbene (75) gave primarily the elimination product, as shown. In this case, the substitution product is likely due to rearrangement of the chlorocarbene.⁴²² It is known that fragmentation of nortricyclyloxychlorocarbene in pentane occurs by an S_Ni-like process to give nortricyclyl chloride.⁴²³ In more polar solvents, fragmentation leads to nortricyclyl cation–chloride anion pair that gives nortricyclyl chloride and a small amount of exo-2-norbornenyl chloride. Fragmentation can also lead to radicals.⁴²⁴

6. Triplet carbenes can abstract hydrogen or other atoms to give free radicals, for example,

This is not surprising, since triplet carbenes are free radicals. But singlet carbenes⁴²⁵ can also give this reaction, although in this case only halogen atoms are abstracted, not hydrogen.⁴²⁶

5.E. Nitrenes

Nitrenes (R–N),427 are the nitrogen analogues of carbenes, and most of the comments about carbenes also applies to them. Nitrenes are too reactive for isolation under ordinary conditions,⁴²⁸ although ab initio calculations show that nitrenes are more stable than carbenes with an enthalpy difference of 25–26 kcal mol⁻¹ (104.7–108.8 kJ mol⁻¹).⁴²⁹

Alkyl nitrenes have been isolated by trapping in matrices at 4 K,⁴³⁰ while aryl nitrenes, which are less reactive, can be trapped at 77 K.⁴³¹ The ground state of NH, and probably of most nitrenes,⁴³² is a triplet, although nitrenes can be generated in both triplet⁴³³ and singlet states. A quartet ground-state nitreno radical has been reported.⁴³⁴ In additions of EtOOC–N to C=C double bonds two species are involved, one of which adds in a stereospecific manner and the other not. By analogy with Skell's proposal involving carbenes (Sec. 5.D.i) these are taken to be the singlet and triplet species, respectively.⁴³⁵

The two principal means of generating nitrenes are analogous to those used to form carbenes.

1. Elimination. An example is

2. Breakdown of Certain Double-Bond Compounds. The most common method of forming nitrenes is photolytic or thermal decomposition of azides,⁴³⁶

The unsubstituted nitrene (NH) has been generated by photolysis of electric discharge through NH₃, N₂H₄, or HN₃.

The reactions of nitrenes are also similar to those of carbenes.⁴³⁷ As in that case, many reactions in which nitrene intermediates are suspected probably do not involve free nitrenes. It is often very difficult to obtain proof in any given case that a free nitrene is or is not an intermediate.

1. Insertion (see Reaction 12-13). Nitrenes, especially acyl nitrenes and sulfonyl nitrenes, can insert into C–H and certain other bonds, for example,

2. Addition to C=C bonds (see Reaction 15-54):

3. Rearrangements.⁴¹³ Alkyl nitrenes do not generally give either of the two preceding reactions because rearrangement is more rapid, for example,

Such rearrangements are so rapid that it is usually difficult to exclude the possibility that a free nitrene was never present at all; that is, that migration takes place at the same time the nitrene is formed⁴³⁸ (see Reaction 18-12). However, the rearrangement of naphthylnitrenes to novel bond-shift isomers has been reported.⁴³⁹

4. Abstraction, For example,

5. Dimerization. One of the principal reactions of NH is dimerization to diimide (N₂H₂). Azobenzenes are often obtained in reactions where aryl nitrenes are implicated:⁴⁴⁰

It would thus seem that dimerization is more important for nitrenes than it is for carbenes, but again it has not been proven that free nitrenes are actually involved.

At least two types of nitrenium ions,⁴⁴¹ the nitrogen analogues of carbocations, can exist as intermediates, although much less work has been done in this area than on carbocations. In one type (76), the nitrogen is bonded to two atoms (R or R′ can be H),⁴⁴² and in the other (77) to only one atom.⁴⁴³ When R = H in 76 the species is a protonated nitrene. Like carbenes and nitrenes, nitrenium ions can exist in singlet or triplet states.⁴⁴⁴

Notes

1. For general references, see Isaacs, N.S. Reactive Intermediates in Organic Chemistry, Wiley, NY, 1974; McManus, S.P. Organic Reactive Intermediates, Academic Press, NY, 1973. Two serial publications devoted to review articles on this subject are Reactive Intermediates (Wiley) and Reactive Intermediates (Plenum).

2. See Olah, G.A.; Schleyer, P.v.R. Carbonium Ions, 5 Vols., Wiley, NY, 1968–1976; Vogel, P. Carbocation Chemistry, Elsevier, NY, 1985. See Saunders, M.; Jiménez-Vázquez, H.A. Chem. Rev. 1991, 91, 375; Arnett, E.M.; Hofelich, T.C.; Schriver, G.W. React. Intermed. (Wiley) 1987, 3, 189. For reviews of dicarbocations, see Lammertsma, K.; Schleyer, P.v.R.; Schwarz, H. Angew. Chem. Int. Ed. 1989, 28, 1321. See also, the series Advances in Carbocation Chemistry.

3. Gomberg, M. Ber. 1902, 35, 2397.

4. For a history of the term “carbonium ion”, see Traynham, J.G. J. Chem. Educ. 1986, 63, 930.

5. Olah, G.A. CHEMTECH 1971, 1, 566; J. Am. Chem. Soc. 1972, 94, 808.

6. Gold, V.; Loening, K.L.; McNaught, A.D.; Sehmi, P. Compendium of Chemical Terminology, IUPAC Recommendations, Blackwell Scientific Publications, Oxford, 1987.

7. Olah, G.A. J. Org. Chem. 2001, 66, 5943. See Olah, G.A.; Prakash, G.K.S. (Eds.), Carbocation Chemistry, Wiley Intersience, Hoboken, NJ, 2004.

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263. Maki, T.; Araki, Y.; Ishida, Y.; Onomura, O.; Matsumura, Y. J. Am. Chem. Soc. 2001, 123, 3371.

264. Jeromin, G.E. Tetrahedron Lett. 2001, 42, 1863.

265. See Novak, I.; Harrison, L.J.; Kova, B.; Pratt, L.M. J. Org. Chem. 2004, 69, 7628.

266. See Anelli, P.L.; Montanari, F.; Quici, S. Org. Synth. 1990, 69, 212; Fritz-Langhals, E. Org. Process Res. Dev. 2005, 9, 577. See also, Rychnovsky, S.D.; Vaidyanathan, R.; Beauchamp, T.; Lin, R.; Farmer, P.J. J. Org. Chem. 1999, 64, 6745.

267. Volodarsky, L.B.; Reznikov, V.A.; Ovcharenko, V.I. Synthetic Chemistry of Stable Nitroxides, CRC Press, Boca Raton, FL, 1994; Keana, J.F.W. Chem. Rev. 1978, 78, 37; Aurich, H.G. Nitroxides. In Nitrones, Nitronates, Nitroxides, Patai, S.; Rappoport, Z., Eds., Wiley, NY, 1989; Chap. 4.

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269. See Ballester, M.; Veciana, J.; Riera, J.; Castañer, J.; Armet, O.; Rovira, C. J. Chem. Soc. Chem. Commun. 1983, 982.

270. Adam, W.; Ortega Schulte, C. M. J. Org. Chem. 2002, 67, 4569.

271. Miura, Y.; Matsuba, N.; Tanaka, R.; Teki, Y.; Takui, T. J. Org. Chem. 2002, 67, 8764. For another stable nitroxide radical, see Huang, W.-l.; Chiarelli, R.; Rassat, A. Tetrahedron Lett. 2000, 41, 8787.

272. Miura, Y.; Tomimura, T.; Matsuba, N.; Tanaka, R.; Nakatsuji, M.; Teki, Y. J. Org. Chem. 2001, 66, 7456. See also, Miura, Y.; Muranaka, Y.; Teki, Y. J. Org. Chem. 2006, 71, 4786; Miura, Y.; Mu, Y. Chem. Lett. 2005, 34, 48

273. Janzen, E.G.; Chen, G.; Bray, T.M.; Reinke, L.A.; Poyer, J.L.; McCay, P.B. J. Chem. Soc. Perkin Trans. 2. 1993, 1983.

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276. Apeloig, Y.; Bravo-Zhivotovskii, D.; Bendikov, M.; Danovich, D.; Botoshansky, M.; Vakulrskaya, T.; Voronkov, M.; Samoilova, R.; Zdravkova, M.; Igonin, V.; Shklover, V.; Struchkov, Y. J. Am. Chem. Soc. 1999, 121, 8118.

277. It has been claimed that relative D values do not provide such a measure: Nicholas, A.M. de P.; Arnold, D.R. Can. J. Chem. 1984, 62, 1850, 1860.

278. Except where noted, these values are from Lide, D.R. (Ed.), Handbook of Chemistry and Physics, 87th ed.; CRC Press: Boca Raton, FL, 2007, pp. 9-60–9-61. For another list of D values, see McMillen, D.F.; Golden, D.M. Annu. Rev. Phys. Chem. 1982, 33, 493. See also, Holmes, J.L.; Lossing, F.P.; Maccoll, A. J. Am. Chem. Soc. 1988, 110, 7339; Holmes, J.L.; Lossing, F.P. J. Am. Chem. Soc. 1988, 110, 7343; Roginskii, V.A. J. Org. Chem. USSR 1989, 25, 403.

279. For the IR of a matrix-isolated phenyl radical, see Friderichsen, A. V.; Radziszewski, J. G.; Nimlos, M. R.; Winter, P. R.; Dayton, D. C.; David, D. E.; Ellison, G. B. J. Am. Chem. Soc. 2001, 123, 1977.

280. For a review of cyclopropyl radicals, see Walborsky, H.M. Tetrahedron 1981, 37, 1625. See also, Boche, G.; Walborsky, H.M. Cyclopropane Derived Reactive Intermediates, Wiley, NY, 1990.

281. This value is from Gutman, D. Acc. Chem. Res. 1990, 23, 375.

282. Zhang, X.-M. J. Org. Chem. 1998, 63, 1872.

283. Brocks, J.J.; Beckhaus, H.-D.; Beckwith, A.L.J.; Rüchardt, C. J. Org. Chem. 1998, 63, 1935.

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287. See Giese, B.; Beckhaus, H. Angew. Chem. Int. Ed. 1978, 17, 594; Ellison, G.B.; Engelking, P.C.; Lineberger, W.C. J. Am. Chem. Soc. 1978, 100, 2556. See, however, Paddon-Row, M.N.; Houk, K.N. J. Am. Chem. Soc. 1981, 103, 5047.

288. There are a few exceptions. See Section 14.A.iv.

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