Chapter 26, Problem 26.47P

Biaryls, compounds containing two aromatic rings joined by a C-C bond, can often be efficiently made by two different Suzuki couplings; that is, either aromatic ring can be used to form the organoborane needed for coupling. In some cases, however, only one route is possible. With this in mind, synthesize each of the following biaryls using benzene as the starting material for each aromatic ring. When more than one route is possible, draw both of them. You may use any required organic or inorganic reagents.

a. b. c.

Interpretation Introduction

(a)

Interpretation: The synthesis of given biaryl compound using benzene as the starting material and any required organic or inorganic reagents is to be stated, and if more than one route is possible, then both routes are to be drawn.

Concept introduction: The treatment of an organic halide $\left({\text{R}}^{\text{'}}\text{X}\right)$ with an organoborane reagent $\left({\text{RBY}}_{\text{2}}\right)$ in the presence of $\text{Pd}$ catalyst to afford the $\text{C}-\text{C}$ coupling is known as Suzuki reaction. During reaction, the metal catalyst is coordinated with some ligands, like ${\text{PPh}}_{\text{3}}$. The reaction is facilitated in the presence of strong inorganic base like ${\text{NaOCH}}_{\text{2}}{\text{CH}}_{\text{3}}$ or $\text{NaOH}$.

Answer to Problem 26.47P

The synthesis of given biaryl compound (two routes) using benzene as the starting material and any required organic or inorganic reagents are shown below.

Explanation of Solution

The treatment of an organic halide $\left({\text{R}}^{\text{'}}\text{X}\right)$ with an organoborane reagent $\left({\text{RBY}}_{\text{2}}\right)$ in the presence of $\text{Pd}$ catalyst to afford the $\text{C}-\text{C}$ coupling is known as Suzuki reaction. During reaction, the metal catalyst is coordinated with some ligands, like ${\text{PPh}}_{\text{3}}$. The reaction is facilitated in the presence of strong inorganic base like ${\text{NaOCH}}_{\text{2}}{\text{CH}}_{\text{3}}$ or $\text{NaOH}$.

The retrosynthetic analysis of the given compound is,

Figure 1

The above analysis shows that there are two possible routes to synthesize the given compound.

Route 1:

The Route 1 involves formation of desired biaryl in nine steps. The first step is Friedel-Crafts alkylation of benzene with ${\text{CH}}_{\text{3}}\text{Cl}$ in the presence of ${\text{AlCl}}_3$ catalyst to yield toluene. The second step is bromination of toluene in the presence of ${\text{FeBr}}_3$ catalyst to yield p-bromotoluene. The third step is treatment of p-bromotoluene with lithium to yield corresponding lithium compound. The fourth step is reaction of lithium compound with trimethyl borate to form an aryl borane (III). The fifth step is chlorination of benzene in the presence of ${\text{FeCl}}_3$ catalyst to yield chlorobenzene. The sixth step is treatment of chlorobenzene with ${\text{NaOH, H}}_{\text{2}}\text{O}$ to yield an alkoxide. The seventh step is methylation of formed alkoxide to yield anisole. The eighth step is bromination of anisole in the presence of ${\text{FeBr}}_3$ catalyst to yield p-bromoanisole (IV). The ninth step is Suzuki reaction between III and IV in the presence of $\text{Pd}{\left({\text{PPh}}_{\text{3}}\right)}_{\text{4}}$ catalyst and $\text{NaOH}$, an inorganic base. These steps are shown below.

Figure 2

Route 2:

The Route 2 involves $\left[\text{10-12}\right]$ steps. The tenth step is treatment of obtained compound in eighth step with lithium to yield corresponding lithium compound. The eleventh step is reaction of this lithium compound with trimethyl borate to yield an aryl borane (II). The twelfth step is Suzuki reaction between obtained compound in second step (I) and (II) to yield the desired biaryl compound. These steps are shown below.

Figure 3

Conclusion

The synthesis of given biaryl compound (two routes) using benzene as the starting material and any required organic or inorganic reagents are shown in Figure 2, and Figure 3.

Interpretation Introduction

(b)

Interpretation: The synthesis of given biaryl compound using benzene as the starting material and any required organic or inorganic reagents is to be stated, and if more than one route is possible, then both routes are to be drawn.

Concept introduction: The treatment of an organic halide $\left({\text{R}}^{\text{'}}\text{X}\right)$ with an organoborane reagent $\left({\text{RBY}}_{\text{2}}\right)$ in the presence of $\text{Pd}$ catalyst to afford the $\text{C}-\text{C}$ coupling is known as Suzuki reaction. During reaction, the metal catalyst is coordinated with some ligands, like ${\text{PPh}}_{\text{3}}$. The reaction is facilitated in the presence of strong inorganic base like ${\text{NaOCH}}_{\text{2}}{\text{CH}}_{\text{3}}$ or $\text{NaOH}$.

Answer to Problem 26.47P

The synthesis of given biaryl compound (two routes) using benzene as the starting material and any required organic or inorganic reagents are shown below.

Explanation of Solution

The treatment of an organic halide $\left({\text{R}}^{\text{'}}\text{X}\right)$ with an organoborane reagent $\left({\text{RBY}}_{\text{2}}\right)$ in the presence of $\text{Pd}$ catalyst to afford the $\text{C}-\text{C}$ coupling is known as Suzuki reaction. During reaction, the metal catalyst is coordinated with some ligands, like ${\text{PPh}}_{\text{3}}$. The reaction is facilitated in the presence of strong inorganic base like ${\text{NaOCH}}_{\text{2}}{\text{CH}}_{\text{3}}$ or $\text{NaOH}$.

The retrosynthetic analysis of the given compound is,

Figure 4

The above analysis shows that there are two possible routes to synthesize the given compound.

Route 1:

The Route 1 involves eight steps. The first step is bromination of benzene in the presence of ${\text{FeBr}}_3$ catalyst to yield bromobenzene (II). The second step is nitration of benzene to yield nitrobenzene. The third step is bromination of nitrobenzene to yield m-bromonitrobenzene. The fourth step is reduction of nitro group of m-bromonitrobenzene by $\text{Sn/HCl}$ to yield m-bromoaniline. The fifth step is diazotization of m-bromoaniline followed by hydrolysis to yield m-bromophenol. The sixth step is conversion of m-bromophenol into corresponding lithium compound (replacement of $\text{Br}$ by $\text{Li}$). The seventh step is treatment of this lithium compound with trimethyl borate to yield an aryl borane (I). The eighth step is Suzuki reaction between (II) and (I) to yield the desired biaryl. These steps are shown below.

Figure 5

Route 2:

The Route 2 involves $\left[\text{9-11}\right]$ steps. The ninth step is treatment of bromobenzene (obtained compound in first step) with lithium to yield phenyllithium. The tenth step is treatment of phenyllithium with trimethyl borate to yield an aryl borane (IV). The eleventh step is Suzuki reaction between the compound obtained in third step (III) and (IV) to yield the desired aryl borane.

Figure 6

Conclusion

The synthesis of given biaryl compound (two routes) using benzene as the starting material and any required organic or inorganic reagents are shown in Figure 5, and Figure 6.

Interpretation Introduction

(c)

Interpretation: The synthesis of given biaryl compound using benzene as the starting material and any required organic or inorganic reagents is to be stated, and if more than one route is possible, then both routes are to be drawn.

Concept introduction: The treatment of an organic halide $\left({\text{R}}^{\text{'}}\text{X}\right)$ with an organoborane reagent $\left({\text{RBY}}_{\text{2}}\right)$ in the presence of $\text{Pd}$ catalyst to afford the $\text{C}-\text{C}$ coupling is known as Suzuki reaction. During reaction, the metal catalyst is coordinated with some ligands, like ${\text{PPh}}_{\text{3}}$. The reaction is facilitated in the presence of strong inorganic base like ${\text{NaOCH}}_{\text{2}}{\text{CH}}_{\text{3}}$ or $\text{NaOH}$.

Answer to Problem 26.47P

The synthesis of given biaryl compound (two routes) using benzene as the starting material and any required organic or inorganic reagents are shown below.

Explanation of Solution

The treatment of an organic halide $\left({\text{R}}^{\text{'}}\text{X}\right)$ with an organoborane reagent $\left({\text{RBY}}_{\text{2}}\right)$ in the presence of $\text{Pd}$ catalyst to afford the $\text{C}-\text{C}$ coupling is known as Suzuki reaction. During reaction, the metal catalyst is coordinated with some ligands, like ${\text{PPh}}_{\text{3}}$. The reaction is facilitated in the presence of strong inorganic base like ${\text{NaOCH}}_{\text{2}}{\text{CH}}_{\text{3}}$ or $\text{NaOH}$.

The retrosynthetic analysis of the given compound is,

Figure 7

The above analysis shows that there are two possible routes to synthesize the given compound.

Route 1:

The Route 1 involves eight steps. The first step is bromination of benzene in the presence of ${\text{FeBr}}_3$ catalyst to yield bromobenzene (I). The second step is chlorination of benzene in the presence of ${\text{FeCl}}_3$ catalyst to yield chlorobenzene. The third step is treatment of chlorobenzene under Dow process to yield phenol. The fourth step is bromination of phenol to form p-bromophenol. The fifth step is esterification of p-bromophenol with ethanoyl chloride to yield p-bromobenzoate. The sixth step is treatment of p-bromobenzoate with lithium to yield the corresponding lithium compound. The seventh step is reaction of lithium compound with trimethyl borate to yield an aryl borane (II). The eighth step is Suzuki reaction between (I) and (II) to yield the desired aryl borane. These steps are shown below.

Figure 8

Route 2:

The Route 2 involves $\left[\text{9-11}\right]$ steps. The ninth step is treatment of bromobenzene (obtained compound in first step) with lithium to yield phenyllithium. The tenth step is treatment of phenyllithium with trimethyl borate to yield an aryl borane (III). The eleventh step is Suzuki reaction between the compound obtained in fifth step (IV) and (III) to yield the desired aryl borane.

Figure 9

Conclusion

The synthesis of given biaryl compound (two routes) using benzene as the starting material and any required organic or inorganic reagents are shown in Figure 8, and Figure 9.