**4. Generation of carbenes**

The synthesis of carbene molecules is generally based on elimination and fragmentation reactions. Carbenes are formed as intermediate products when groups attached to the carbon atom are broken as a result of photolysis, thermolysis or reaction with metals.

#### **4.1 Fragmentation reactions**

Diazo compounds, tosylhydrazones, ketenes, three-membered carbon rings, strained alkenes and heterocyclic compounds are generally used as carbene precursors in fragmentation reactions.

#### *4.1.1 Diazo compounds*

Diazo compounds (RR'C=N2), constitute a principal class of carbene precursors, known since the first preparation of ethyl diazoacetate by Curtius in 1883 [24]. Diazo compounds, which have 1,3-dipolar structures (**Figure 5a**), are generally converted to related carbenes by easily removing nitrogen gas when heated or photolyzed in aprotic solvents as shown in **Figure 5b**. This conversion has been proven by spectroscopic methods. The electronic spectrum of methylene produced in the gas phase by flash photolysis of diazomethane was recorded by Herzberg and Shoosmith [25]. Various metal complexes are used as catalyst for carbene formation to occur at low temperatures. Since diazo compounds are generally unstable and easily degradable compounds, they must be synthesized before each reaction.

#### **Figure 5.**

*(a) Resonance structure of 1,3-dipolar diazo compound. (b) Generation of carbene from diazo compounds.*

Diazo compounds, which have a unique reactivity due to their 1,3-dipole and ylide structures, are useful synthetic products in organic synthesis. However, their large-scale use has been avoided due to their toxicity and unpredictable explosive behavior [26].

#### *4.1.2 Tosylhydrazones*

Where the diazo compound is somehow unstable and dangerous to use, it is usually better to use a diazo precursor. The simplest and most common compounds used for this are hydrazones. Ketones and aldehydes easily react with hydrazine to form hydrazone compounds. The oxidation of hydrazones with metal salts such as Ag2O, HgO, MnO2, Pb(OAc)4 gives the diazo compound (**Figure 6**).

The most widely known and used carbene precursors are tosylhydrazones which are prepared from the reaction of aldehydes and ketones with p-toluenesulphonyl hydrazide.

*Carbene*

**Figure 6.** *Generation of carbenes from hydrazones compound.*

p-Toluenesulpnonylhydrazones (tosylhydrazones) of aldehydes and ketones undergo base-catalyzed thermal decomposition with loss of p-toluenesulfinate to give intermediate diazo compounds [27]. This method is called the Bamford-Stevens reaction (**Figure 7**).

**Figure 7.** *Bamford-Stevens reaction.*

When the N-H proton in the tosylhydrazone molecule is removed with a base such as NaH or NaOCH3, the formed anion is stabilized by the tosyl group. Therefore, the resulting salt can be isolated and stored for a long time. This salt can be converted to carbene by heating at any time in situ. After the nitrogen gas is separated, alkene formation is observed as a result of 1,2-hydrogen shift. When the alkene formation mechanism was examined comprehensively, it was found that the products formed may vary depending on the reaction conditions [28]. In the Bamford-Stevens reaction, if the decomposition of the tosylhydrazone salt is done in aprotic solvents, carbene is formed by the removal of nitrogen gas. The resulting carben usually forms an alkene as a result of 1,2-hydrogen shift. However, if the salt is decomposed in protic solvents, the diazonium salt is formed first. Diazonium salts, especially the aliphatic ones, are not stable, they turn into carbenium ions by removing nitrogen gas.

*Basic Information about Carbenes DOI: http://dx.doi.org/10.5772/intechopen.100425*

#### *4.1.3 Ketenes*

Ketenes can eliminate CO molecule on thermolysis or photolysis to generate carben. Since ketenes are not readily available precursor and polymerize under the reaction conditions, they are not widely used. Ketene has been used extensively to generate CH2.

$$\mathbf{c}\mathbf{^{\mathcal{R}}\_{\mathsf{B}}} \xrightarrow[\mathsf{GC}\mathbf{^{\mathcal{R}}}]{} \mathbf{^{\bullet}\_{\mathsf{F}}} \mathbf{^{\bullet}\_{\mathsf{F}}} \mathbf{^{\bullet}\_{\mathsf{F}}} \mathbf{^{\bullet}\_{\mathsf{B}}}$$

#### *4.1.4 Three-membered carbon ring*

Three-membered rings that have a high ground state energy due to steric strain often decompose to give carbene intermediates by heating or irradiation. For example; photolysis of 1,1-dichloro-2-phenylcyclopropane apparently gives CCl2 and photolytic decomposition of oxiranes yield arylcarbenes and related species as shown in **Figure 8**.

Substituted phenyloxiranes provide convenient precursors for substituted arylcarbenes, such as diphenylcarbene [29], phenylmethylcarbene [30], cyanophenylcarbene [31, 32], and methoxycarbonylphenylcarbene [33]. Selective cleavage was observed with unsymmetrical precursors, the thermodynamically more stable isomer appears to be favored.

#### **Figure 8.**

*Generation of carbene from cyclopropanes and epoxides.*

The most useful carbene precursors of the three-membered ring are diazirines. Diazirines, the cyclic isomers of diazoalkanes, also decompose under the influence of heat and light to give carbenes [34–37]. As shown in **Figure 9**, they are prepared from ketones by reaction with ammonia and chloramine followed by oxidation of the resulting diaziridine. This method is quite widely used especially for halocarbenes.

#### **Figure 9.** *Preparation and decomposition of diazirines.*

#### *4.1.5 Strained alkenes*

If the alkene is extremely sterically hindered then the π-bond is weakend due to the substantially reduced p–p overlap and distortion from planarity. As a result, the ground state energy is raised and then dissociation to carbenes become possible by heating. The well-known example of this process is the reversible dissociation of tetranaphth-1-ylethene into bis(naphth-1-yl) carbene at 250°C [38] (**Figure 10**).

**Figure 10.** *Thermal dissociation of tetranaphth-1-ylethene.*

#### *4.1.6 Heterocycles*

Various five-membered heterocyclic compounds decompose to give carbenes by heating or irradiation (**Figure 11**). The decomposition of 1,5-dihydro-1,3,4 oxadiazoles give carbenes at about 80°C with loss of nitrogen followed by the carbonyl fragment.

**Figure 11.** *Fragmentation of five-membered heterocycles to carbenes.*

## **4.2 α-Elimination**

The hydrolysis of chloroform in basic medium was probably the first reaction in which intermediate carbene formation was suggested by Geuther [39]. The investigation the mechanism of this reaction by Hine and co-workers initiated the modern era of carben chemistry in the early 1950s [40–42]. In the basic environment, the acidic proton of chloroform separates and trichloromethyl anion is formed.

*Basic Information about Carbenes DOI: http://dx.doi.org/10.5772/intechopen.100425*

Dichlorocarbene is formed as a result of the removal of the chloride anion from the carbanion. By hydrolysis of dichlorocarbene in aqueous media, carbon monoxide is formed (**Figure 12**). These types of reactions are called α-elimination reactions because the hydrogen and chlorine released in the formation of carbene are attached to the same carbon atom.

$$\begin{array}{ccccccccc} \text{Cl}^{-} & \text{Cl}^{-} & & & \text{Cl}^{2} \\ & & & \text{Cl}^{2} & & \\ \text{Cl}^{2} & & & \text{Cl}^{2} & & \\ & & & \text{Cl}^{2} & & \\ & & & & \text{Cl}^{2} & \\ \end{array} \quad \begin{array}{ccccccccc} \text{Cl}^{-} & & & \text{Cl}^{2} & & \\ & & & \text{Cl}^{2} & & \\ & & & \text{Cl}^{2} & & \\ & & & \text{Cl}^{2} & & \\ & & & \text{Cl}^{2} & & \\ \end{array} \quad \begin{array}{ccccccccc} \text{Cl}^{-} & & & \text{Cl}^{2} & & \\ & & & \text{Cl}^{2} & & \\ & & & \text{Cl}^{2} & & \\ & & & \text{Cl}^{2} & & \\ \end{array}$$

**Figure 12.** *α-Elimination reactions.*

In experiments with aprotic solvents and strong bases, it was determined that carbene was formed and added to the double bond electrons to form cyclopropane derivatives as shown in **Figure 13**. This reaction is the best method for cyclopropane synthesis in organic chemistry.

$$\text{3.3.} \xrightarrow[]{\text{C}} \text{ \downarrow\text{C}}^{\text{\downarrow\text{C}}} \text{ \downarrow\text{C}}^{\text{\downarrow\text{C}}} \xrightarrow[]{\text{A}} \text{8.08}^{\text{\downarrow\text{C}}} \text{ + } \text{H}\_{\text{C}}^{\text{\downarrow\text{C}}}$$

**Figure 13.** *Cyclopropane synthesis.*

Before the reaction, the solvent used must be dried very well. Because the water in the environment can easily react with the carbene formed, and it also reacts with the base in the environment and completely prevents the formation of carbenes. However, in Makosza, a study carried out in a two-phase system, showed that carbenes were formed in the presence of phase transfer catalysts in aqueous medium and added to double bonds (**Figure 14**) [43].

**Figure 14.** *Carbene formation in a two-phase system.*

Since the reaction is between two phases, effective mixing is very important for this reaction. Although the reaction is carried out in the presence of water, the carbene is generated and reacts in the organic phase.

#### *4.2.1 Simmon-Smith reaction*

It is not possible to synthesize methylene carbene by the α-elimination method. However, there are methods that form methylene carbene adducts. The most commonly used method is the reaction of alkenes with diiodomethane in the presence of zinc. As a result of the reaction, cyclopropane compounds are formed (**Figure 15**) [44, 45].

**Figure 15.** *Simmon-Smith reaction.*

During this reaction, methylene carbene is not formed in the free form. First, zinc and diiodomethane react to form a carbenoid intermediate, which acts as a carbene. Later, since this product is unstable, it transforms into zinc iodide by transferring the methylene group to the double bond as shown in **Figure 16** [46].

**Figure 16.** *Mechanism of Simmon-Smith reaction.*

#### **5. Carbene reactions**

Singlet and triplet carbene exhibit different reactivity. Singlet carbenes generally participate in reactions as either electrophiles or nucleophiles. Singlet carbenes which have unfilled p-orbitals should be electrophilic. Triplet carbenes can be considered as diradicals and participate in stepwise radical additions. Triplet carbenes must pass through an intermediate with two unpaired electrons, while single carbenes can react in a single concerted step. Because carbenes have two modes of reactivity, singlet methylene gives stereospecific reactions where as triplet methylene gives stereoselective reactions [47].

Carbenes are highly reactive intermediate due to electron deficiency. Carbenes react instantly in various ways in the environment where they are formed. Carbene reactions are classified under four main groups.

#### **5.1 Cycloaddition reaction of carbenes**

Since carbenes generally react electrophilically, they give a [2 + 2] cycloaddition reaction with double bonds to form cyclopropane compounds (**Figure 17**). This

*Basic Information about Carbenes DOI: http://dx.doi.org/10.5772/intechopen.100425*

**Figure 17.** *Cycloaddition reaction of carbenes.*

method, the most characteristic reaction of carbene intermediates, has now been widely used as a synthetic route to cyclopropane since 1954 [6].

According to the theory proposed by Skell and Woodworth [47], singlet carbenes are added the double bonds simultaneously in a single step. The opening of double bond electrons and the formation of new carbon–carbon bonds occur simultaneously. On the other hand, triplet carbenes are not added in double bonds in a single step because this addition is forbidden by orbital symmetry. Triplet carbenes form cyclopropane compounds by adding double bonds as a result of a multi-step reaction.

Since carbenes are generally electrophilic compounds, they prefer double bonds where the electron density is high when adding systems that contain more than one double bond. In particular, singlet carbenes (dihalocarbenes) show more regioselective properties as they are more stable. For example, in the isotetralin compound, which has two different double bonds, dihalocarbene selectively adds the central double bond, although it has a steric hindrance. However, the more reactive ethoxycarbonylcarbene cannot act selectively due to its shorter lifetime and adds the double bonds located on the outer part of the molecule as shown below.

#### **5.2 Dimerization reaction of carbenes**

When carbenes cannot find a reagent that can react in the environment in which they are formed, they dimerize to fill the electron gap in their outer orbitals and turn into olefins (**Figure 18**).

**Figure 18.** *Dimerization reaction of carbenes.*

#### **5.3 Insertion reaction of carbenes**

Another characteristic reaction that carbenes give to become stable is that carbenes insert between C-H or C-C bonds (**Figure 19**).

**Figure 19.** *Examples of carbene insertion reaction.*

Methylene, when there is no double bond to react it is not selective and insert into a random C-H bond in the liquid phase. Methylene acts selectively in the gas phase and preferentially inserts into tertiary C-H bonds as shown in **Figure 20**.

**Figure 20.** *Insertion of methylene.*

The electronic structure of carbene plays an important role in the insertion reactions (**Figure 21**). Singlet carbenes generally insert into bonds in a single step with retention of configuration. The situation is different with triplet carbenes. Since triplet carbenes act as radicals, they first abstract hydrogen from the C-H bond and form two new radicals. With the combination of these radicals, a new C-C bond is formed. Meanwhile, as the radical configuration undergoes isomerization, a racemic mixture is formed as a result of the reaction. In the insertion of triplet carbenes, tertiary carbon-hydrogen bonds are primarily preferred because they form stable radicals.

**Figure 21.** *Mechanism of singlet and triplet carbene in the insertion reaction.*
