Question

Give structures of all compounds below: (a) \(p\) -nitrophenol \(+\mathrm{C}_{2} \mathrm{H}_{5} \mathrm{Br}+\mathrm{NaOH}(\mathrm{aq}) \rightarrow \mathrm{A}\left(\mathrm{C}_{8} \mathrm{H}_{9} \mathrm{O}_{3} \mathrm{~N}\right)\) \(\mathrm{A}+\mathrm{Sn}+\mathrm{HCL} \rightarrow \mathrm{B}\left(\mathrm{C}_{8} \mathrm{~B}_{11} \mathrm{ON}\right)\) \(\mathrm{B}+\mathrm{NaNO}_{2}+\mathrm{HCL}\), then phenol \(\rightarrow \mathrm{C}\left(\mathrm{C}_{14} \mathrm{H}_{14} \mathrm{O}_{2} \mathrm{~N}_{2}\right)\) \(\mathrm{C}+\) ethyl sulfate \(+\mathrm{NaOH}\) (aq) \(\rightarrow \mathrm{D}\left(\mathrm{C}_{16} \mathrm{H}_{18} \mathrm{O}_{2} \mathrm{~N}_{2}\right)\) \(\mathrm{D}+\mathrm{SnCL}_{2} \rightarrow \mathrm{E}\left(\mathrm{C}_{8} \mathrm{H}_{11} \mathrm{ON}\right)\) \(E+\) acetyl chloride phenacetin \(\left(\mathrm{C}_{10} \mathrm{H}_{13} 2 \mathrm{~N}\right)\), an analgesic ("pain-killer") and antypyretic ("fever- killer") (b) \(\beta-(-0-\) hy droxyphenyl \()\) ethyl alcohol \(+\mathrm{HBr} \rightarrow \mathrm{F}\left(\mathrm{C}_{8} \mathrm{H}_{9} \mathrm{OBr}\right)\) \(\mathrm{F}+\mathrm{KOH} \rightarrow\) coumarane \(\left(\mathrm{C}_{8} \mathrm{H}_{8} \mathrm{O}\right)\), insoluble in \(\mathrm{NaOH}\).

Short answer

In summary, we have determined the structures of the compounds produced at each stage of the reaction series. The formation of various functional groups, such as ethers, amines, and azo compounds, were observed throughout the process. The final products include the analgesic and antipyretic agent Phenacetin, and Coumarane, a chromene derivative insoluble in NaOH.

Step-by-step solution

Reaction of p-nitrophenol with ethyl bromide and NaOH (aqueous)

In this step, p-nitrophenol reacts with ethyl bromide and NaOH (aqueous). p-nitrophenol has an -OH group, which can act as a nucleophile, and ethyl bromide has a good leaving group (Br-). When treated with a strong base like NaOH, the phenoxide ion is formed, which is a strong nucleophile and will displace the leaving group Br- from ethyl bromide to form compound A with the formula C8H9O3N: p-nitrophenol + C2H5Br + NaOH (aq) → A (C8H9O3N) **Structure of Compound A**: 4-nitrophenyl ethyl ether: \(C_{6}H_{4}(NO_{2})(OCH_{2}CH_{3})\)

Reaction of compound A with Sn and HCl

Compound A (nitro group) can be reduced when reacted with Sn and HCl, generating the aniline derivative, compound B with the formula C8H11ON: A + Sn + HCl → B (C8H11ON) **Structure of Compound B**: p-anisidine: \(C_{6}H_{4}(NH_{2})(OCH_{2}CH_{3})\)

Reaction of compound B with NaNO2, HCl and phenol

When compound B is treated with NaNO2 and HCl, it forms a diazonium salt, which then reacts with phenol to produce the azo compound C with the formula C14H14O2N2: B + NaNO2 + HCl → Diazo Diazo + Phenol → C (C14H14O2N2) **Structure of Compound C**: p-[(4-anisyl)azo]phenol: \(C_{6}H_{4}(N=NC_{6}H_{4}(OH))(OCH_{2}CH_{3})\)

Reaction of compound C with ethyl sulfate and NaOH (aq)

When compound C is treated with ethyl sulfate and NaOH (aq), an ethoxy group is added to the phenolic OH, forming compound D with the formula C16H18O2N2: C + Ethyl sulfate + NaOH (aq) → D (C16H18O2N2) **Structure of Compound D**: p-anisylazophenetole: \(C_{6}H_{4}(N=NC_{6}H_{4}(OC_{2}H_{5}))(OCH_{2}CH_{3})\)

Reaction of compound D with SnCl2

When reacted with SnCl2, the azo group in compound D is reduced to form compound E with the formula C8H11ON: D + SnCl2 → E (C8H11ON) **Structure of Compound E**: Ethyl p-anisidinium chloride : \(C_{6}H_{4}(NH_{2})(OCH_{2}CH_{3})\)

Reaction of compound E with acetyl chloride

Compound E reacts with acetyl chloride to form phenacetin, an analgesic and antipyretic agent, with the formula C10H13NO2: E + Acetyl chloride → Phenacetin (C10H13NO2) **Structure of Phenacetin**: \(C_{6}H_{4}(NHCOCH_{3})(OCH_{2}CH_{3})\)

Reaction of β-(o-hydroxyphenyl)ethyl alcohol with HBr

When β-(o-hydroxyphenyl)ethyl alcohol reacts with HBr, compound F with the formula C8H9OBr is formed: β-(o-hydroxyphenyl)ethyl alcohol + HBr → F (C8H9OBr) **Structure of Compound F**: o-bromophenylethanol: \(C_{6}H_{4}(BrCH_{2}CH_{2}OH)\)

Reaction of compound F with KOH

Compound F reacts with KOH to form coumarane, which is insoluble in NaOH, with the formula C8H8O: F + KOH → Coumarane (C8H8O) **Structure of Coumarane**: Chromene: \(C_{6}H_{4}(OCH=CH2)\)

Key concepts

Nucleophilic Substitution

Nucleophilic substitution is a fundamental type of reaction in organic chemistry, where a nucleophile, an electron-rich species, displaces a leaving group, typically an electron-poor atom or group of atoms, on a carbon atom.

In the given exercise, p-nitrophenol undergoes nucleophilic substitution with ethyl bromide in the presence of NaOH. NaOH deprotonates the hydroxyl group of p-nitrophenol, forming a phenoxide ion, a potent nucleophile. This phenoxide ion then replaces the bromide ion in ethyl bromide to form compound A, which is a 4-nitrophenyl ethyl ether.

The success of this transformation hinges on the stability of the leaving group (Br-) and the strength of the nucleophile (phenoxide ion). Similar reactions are common in the synthesis of ethers and other organic compounds, where alcohols are converted into better leaving groups, making them susceptible to attack by nucleophiles.

Reduction of Nitro Compounds

The reduction of nitro compounds to amines is a pivotal reaction in the preparation of various pharmaceuticals and dyes. This chemical transformation involves the conversion of a nitro group (\textbf{NO}\(_2\)) into an amino group (\textbf{NH}\(_2\)).

In our solution, compound A containing a nitro group is reduced using tin (Sn) and hydrochloric acid (HCl) to yield compound B, p-anisidine. This process typically involves multiple electrons and protons and can be carried out using different reducing agents such as metals in acidic conditions, catalysts like palladium on carbon, or chemical reductants like iron.

Reductions like this are critical in the preparation of aniline derivatives, which serve as building blocks for the synthesis of more complex organic molecules.

Diazonium Salt Reactions

Diazonium salts are valuable intermediates in synthetic chemistry, especially in the synthesis of azo compounds, which are characterized by a nitrogen-to-nitrogen double bond (\textbf{N}\(=\)\textbf{N}). The formation of diazonium salts typically involves the reaction of primary aromatic amines with nitrous acid (\textbf{HNO}\(_2\)), generated in situ from sodium nitrite (\textbf{NaNO}\(_2\)) and a strong acid such as hydrochloric acid (HCl).

Compound B, p-anisidine, reacts with NaNO\(_2\) and HCl to form a diazonium salt. Diazonium salts are versatile and can engage in a variety of reactions such as azo coupling, Sandmeyer reactions, and Schiemann reactions, leading to the synthesis of diverse aromatic compounds. The robustness of diazonium chemistry lies in the ability to introduce various functional groups into aromatic rings under mild conditions.

Azo Coupling

Azo coupling is an important organic reaction where a diazonium salt reacts with another aromatic compound to form an azo derivative, a compound containing the \textbf{N}\(=\)\textbf{N} azo group. This reaction is widely used to synthesize azo dyes, which are intensely colored and find applications in coloring textiles and as pigments.

Compound B undergoes azo coupling with phenol to form compound C, an azo compound. The electron-rich aromatic ring of phenol attacks the electrophilic diazonium ion to create a new \textbf{N}\(=\)\textbf{N} bond. The regioselectivity of this reaction is governed by the electronic properties of the reacting aromatic systems, and often ortho and para substitution positions are favored.

Ethylation Reactions

Ethylation in organic chemistry is a process of introducing an ethyl group into a molecule. It's a subtype of alkylation, which overall means adding an alkyl group to a compound.

The reaction of compound C with ethyl sulfate and NaOH, as mentioned in the solution, is a classic example of ethylation. Compound C, containing an azo group and a phenolic OH, reacts with ethyl sulfate, a good alkylating agent, in the presence of a strong base (NaOH). This results in compound D, where the phenolic oxygen has been ethylated to form p-anisylazophenetole. Such reactions are crucial for modifying the properties of molecules, such as enhancing solubility or altering biological activity and are often used in pharmaceutical chemistry to modify drug molecules.