Question

Outline all steps in a possible laboratory synthesis of each of the following, using benzene, toluene, and any needed aliphatic or inorganic reagents. (a) p-bromobenzyl chloride (b) triphenylchloromethane (c) allyl iodide (d) benzal bromide (e) \(\mathrm{m}\) -nitrobenzotrichloride (f) 1,2 -dichloro-1- phenylethane (g) phenylacetylene (h) phenylcyclopropane

Short answer

(a) p-bromobenzyl chloride synthesis: 1. Friedel-Crafts Alkylation of benzene with 1-chloropropane (AlCl3 catalyst). 2. Bromination of propylbenzene (Br2, FeBr3 catalyst). 3. Chlorination of p-bromopropylbenzene (SOCl2). (b) triphenylchloromethane synthesis: 1. Friedel-Crafts Alkylation of benzene with chloroform (CHCl3, AlCl3 catalyst). (c) allyl iodide synthesis: 1. Preparation of allyl chloride (propene + Cl2). 2. Halogen exchange reaction (KI). (d) benzal bromide synthesis: 1. Gattermann-Koch reaction (benzene, CO, HCl, AlCl3, CuCl catalysts). 2. Bromination (benzaldehyde + PBr3). (e) m-nitrobenzotrichloride synthesis: 1. Nitration (benzene, HNO3, H2SO4). 2. Trichlorination (m-nitrobenzene, Cl2, AlCl3 or FeCl3 catalyst). (f) 1,2-dichloro-1-phenylethane synthesis: 1. Friedel-Crafts Alkylation (benzene, 1,2-dichloroethane, AlCl3 catalyst). (g) phenylacetylene synthesis: 1. Birch reduction (benzene, Na, NH3, ethanol). 2. Bromination (1,4-cyclohexadiene, NBS). 3. Corey-Fuchs reaction (1-bromo-4-cyclohexene, PPh3, CCl4). (h) phenylcyclopropane synthesis: 1. Simmons-Smith reaction (styrene, CH2I2, Zn-Cu couple catalyst).

Step-by-step solution

(a) p-bromobenzyl chloride synthesis

1. Friedel-Crafts Alkylation: React benzene with 1-chloropropane in the presence of an aluminum chloride catalyst (AlCl3) to form propylbenzene. 2. Bromination: React propylbenzene with bromine (Br2) and iron(III) bromide (FeBr3) catalyst to form p-bromopropylbenzene. 3. Chlorination: React p-bromopropylbenzene with thionyl chloride (SOCl2) to replace the bromine with a chlorine atom, resulting in the final product, p-bromobenzyl chloride.

(b) triphenylchloromethane synthesis

1. Friedel-Crafts Alkylation: React benzene with chloroform (CHCl3) and anhydrous aluminum chloride (AlCl3) as a catalyst to produce triphenylchloromethane.

(c) allyl iodide synthesis

1. Preparation of allyl chloride: React propene with Cl2 to form allyl chloride. 2. Halogen exchange reaction: Treat the allyl chloride with potassium iodide (KI) to produce allyl iodide.

(d) benzal bromide synthesis

1. Gattermann-Koch reaction: React benzene with carbon monoxide (CO) and hydrogen chloride (HCl) in the presence of an aluminum chloride (AlCl3) and cuprous chloride (CuCl) catalyst to form benzaldehyde. 2. Bromination: Treat benzaldehyde with phosphorus tribromide (PBr3) to form benzal bromide.

(e) m-nitrobenzotrichloride synthesis

1. Nitration: Treat benzene with nitric acid (HNO3) and sulfuric acid (H2SO4) to form m-nitrobenzene. 2. Trichlorination: Treat m-nitrobenzene with chlorine (Cl2) and a Lewis acid catalyst such as aluminum chloride (AlCl3) or iron(III) chloride (FeCl3) to form m-nitrobenzotrichloride.

(f) 1,2-dichloro-1-phenylethane synthesis

1. Friedel-Crafts Alkylation: React benzene with 1,2-dichloroethane and aluminum chloride (AlCl3) catalyst to form 1,2-dichloro-1-phenylethane.

(g) phenylacetylene synthesis

1. Birch reduction: Reduce benzene to 1,4-cyclohexadiene using sodium metal (Na) and liquid ammonia (NH3) in the presence of an alcohol, such as ethanol. 2. Bromination: React 1,4-cyclohexadiene with N-bromosuccinimide (NBS) to form 1-bromo-4-cyclohexene. 3. Corey-Fuchs reaction: Treat the 1-bromo-4-cyclohexene with two equivalents of triphenylphosphine (PPh3) and one equivalent of carbon tetrachloride (CCl4) to form phenylacetylene.

(h) phenylcyclopropane synthesis

1. Simmons-Smith reaction: React styrene (vinylbenzene) with diiodomethane (CH2I2) and a zinc-copper couple catalyst to form phenylcyclopropane.

Key concepts

Friedel-Crafts Alkylation

Friedel-Crafts Alkylation is a popular reaction in organic chemistry commonly used to attach alkyl groups to an aromatic ring, such as benzene. This process uses catalysts called Lewis acids, which include Aluminum Chloride (AlCl3), to activate the alkyl halide.

During the reaction, the Lewis acid forms a complex with the alkyl halide, creating a carbocation. This positively charged species then attacks the electron-rich benzene, resulting in the alkylation of the benzene ring.

• For example, in synthesizing p-bromobenzyl chloride, benzene is reacted with 1-chloropropane in the presence of AlCl3 to form propylbenzene.
• Similarly, for triphenylchloromethane, benzene reacts with chloroform under AlCl3 catalysis.

Understanding the mechanism of Friedel-Crafts Alkylation is essential for efficiently synthesizing complex organic compounds in the lab.

Bromination

Bromination is a chemical reaction used to introduce a bromine atom into an organic compound. Typically, bromination reactions are used to add bromine to aromatic compounds. The presence of a catalyst, such as iron(III) bromide (FeBr3), facilitates the reaction by promoting the formation of a bromonium ion.

In organic synthesis, bromination can achieve selective substitutions on an aromatic ring. The most substituted position on the aromatic compound is often favored, particularly in reactions that proceed by a radical mechanism.

• During the synthesis of p-bromobenzyl chloride, bromination of propylbenzene with Br2 and FeBr3 yields p-bromopropylbenzene.
• In another example, benzal bromide synthesis involves the introduction of a bromine atom into benzaldehyde through a reaction with phosphorus tribromide (PBr3).

Thus, understanding bromination is important for effectively introducing bromine into desired positions in organic molecules.

Chlorination

Chlorination is a versatile reaction used to add chlorine atoms to organic molecules. It can target various functional groups, facilitating transformations such as replacing hydrogen atoms or other halogens. Chlorine can be added to both aliphatic and aromatic compounds. The reaction typically proceeds through a radical or electrophilic mechanism.

For instance, chlorination plays a role in synthesizing p-bromobenzyl chloride, where thionyl chloride (SOCl2) replaces an existing bromine atom with chlorine in the p-bromopropylbenzene intermediate.

• This step is crucial to converting the intermediate compound to the final product.
• Chlorination often requires careful control to ensure selectivity and avoid over-chlorination.

Overall, chlorination is a key tool in organic synthesis, capable of generating important compounds by altering the halogen content of molecules.

Reagents and Catalysts

Reagents and catalysts play a pivotal role in organic synthesis, often determining the success and specificity of a reaction. Reagents are substances added to cause a chemical reaction, while catalysts are substances that accelerate the reaction without being consumed.

Different reactions utilize different reagents and catalysts. For example, in Friedel-Crafts Alkylation, anhydrous Aluminum Chloride (AlCl3) is used as a catalyst to promote the formation of carbocations.

• Bromination reactions often employ bromine (Br2) with an iron(III) bromide (FeBr3) catalyst to facilitate the substitution of bromine into aromatic rings.
• Chlorination may use reagents like thionyl chloride (SOCl2).

Choosing the appropriate combination of reagents and catalysts is critical in conducting efficient and effective organic synthesis.