Question

Outline a possible laboratory synthesis of each of the following compounds from alcohols and phenols: (a) methy1 tert-buty 1 ether (b) n-propy1 phenyl ether (c) cyclohexy1 methy1 ether

Short answer

To synthesize the three ethers using alcohols and phenols, we utilize the Williamson ether synthesis method: (a) To synthesize methyl tert-butyl ether, use methanol and tert-butyl chloride. Deprotonate methanol to form the methoxide ion and react it with tert-butyl chloride to yield methyl tert-butyl ether. (b) To synthesize n-propyl phenyl ether, use phenol and n-propyl bromide. Deprotonate phenol to form the phenoxide ion and react it with n-propyl bromide to yield n-propyl phenyl ether. (c) To synthesize cyclohexyl methyl ether, use cyclohexanol and methyl iodide. Deprotonate cyclohexanol to form the cyclohexoxide ion and react it with methyl iodide to yield cyclohexyl methyl ether.

Step-by-step solution

(a) Synthesis of methyl tert-butyl ether

Step 1: Choose the appropriate alcohols and phenols Select a combination of an alcohol and an alkyl halide. In this case, you would need methanol (CH3OH) and tert-butyl chloride (CH3)3CCl. Step 2: Formation of the alkoxide Deprotonate methanol with a strong base, like sodium hydride (NaH), to form the methoxide ion (CH3O−). \[ CH_{3}OH + NaH \rightarrow CH_{3}O^{-}Na^{+} + H_{2} \] Step 3: Williamson ether synthesis Perform the Williamson ether synthesis by mixing the methoxide ion with tert-butyl chloride. The reaction yields methyl tert-butyl ether. \[ CH_{3}O^{-}Na^{+} + (CH_{3})_{3}CCl \rightarrow (CH_{3})_{3}COCH_{3} + NaCl \]

(b) Synthesis of n-propyl phenyl ether

Step 1: Choose the appropriate alcohols and phenols Select a combination of a phenol and an alkyl halide. In this case, you would need phenol (C6H5OH) and n-propyl bromide (CH3CH2CH2Br). Step 2: Formation of the phenoxide Deprotonate phenol with a strong base, like sodium hydroxide (NaOH), to form the phenoxide ion (C6H5O-). \[ C_{6}H_{5}OH + NaOH \rightarrow C_{6}H_{5}O^{-}Na^{+} + H_{2}O \] Step 3: Williamson ether synthesis Perform the Williamson ether synthesis by mixing the phenoxide ion with n-propyl bromide. The reaction yields n-propyl phenyl ether. \[ C_{6}H_{5}O^{-}Na^{+} + CH_{3}CH_{2}CH_{2}Br \rightarrow C_{6}H_{5}OCH_{2}CH_{2}CH_{3} + NaBr \]

(c) Synthesis of cyclohexyl methyl ether

Step 1: Choose the appropriate alcohols and phenols Select a combination of an alcohol and an alkyl halide. In this case, you would need cyclohexanol (C6H11OH) and methyl iodide (CH3I). Step 2: Formation of the cyclohexoxide Deprotonate cyclohexanol with a strong base, like potassium tert-butoxide (t-BuOK), to form the cyclohexoxide ion (C6H11O-). \[ C_{6}H_{11}OH + t-BuOK \rightarrow C_{6}H_{11}O^{-}K^{+} + t-BuOH \] Step 3: Williamson ether synthesis Perform the Williamson ether synthesis by mixing the cyclohexoxide ion with methyl iodide. The reaction yields cyclohexyl methyl ether. \[ C_{6}H_{11}O^{-}K^{+} + CH_{3}I \rightarrow C_{6}H_{11}OCH_{3} + KI \]

Key concepts

Synthesis of Ethers

Ethers are a versatile class of organic compounds characterized by an oxygen atom connecting two alkyl or aryl groups. They are commonly used as solvents, fuel additives, and in the synthesis of other chemicals. In the laboratory, ethers can be synthesized using the Williamson ether synthesis. This process involves the reaction of an alkoxide ion with a primary alkyl halide. This reaction is particularly useful because it can be used to create a wide variety of ether molecules with different alkyl or aryl groups, offering considerable flexibility in the design of organic syntheses.

For instance, to create methyl tert-butyl ether, methoxide, an alkoxide ion derived from methanol, reacts with tert-butyl chloride. In the case of n-propyl phenyl ether, phenoxide ion from phenol joins with n-propyl bromide. Lastly, for cyclohexyl methyl ether synthesis, one combines cyclohexoxide ion, derived from cyclohexanol, with methyl iodide. The general approach in each of these reactions is to first generate an alkoxide ion and then to engage in the ether-forming step.

Alkoxide Formation

Central to the synthesis of ethers is the formation of alkoxide ions. Alkoxide ions are the conjugate bases of alcohols and are essential intermediates in the Williamson ether synthesis. The process of forming an alkoxide involves deprotonating an alcohol with a strong base.

For instance, when sodium hydride (NaH) is used to deprotonate methanol, the reaction yields a methoxide ion along with hydrogen gas. The choice of base is crucial as it must be strong enough to remove a proton from the alcohol, which is a relatively weak acid. Common bases used in this process include sodium hydride, potassium hydride, and sodium or potassium alkoxides. Each base is chosen for its ability to effectively deprotonate specific types of alcohols to generate the desired alkoxide ion.

Ether Synthesis from Alcohols and Phenols

The synthesis of ethers typically starts with alcohols or phenols because they have hydroxyl groups that can be converted into reactive alkoxide or phenoxide ions. The conversion of alcohols into ethers is a two-step process. First, one transforms the alcohol into its corresponding alkoxide ion, which acts as a nucleophile. In the next step, this nucleophile attacks an electrophilic alkyl halide to form the ether linkage.

Similarly, phenols can be converted into ethers through a similar process. The phenol is deprotonated to generate a phenoxide ion, which is then reacted with an alkyl halide to produce the aryl ether. This versatility allows chemists to create a vast array of ethers from readily available starting materials, making it a valuable method in organic chemistry.

Strong Bases in Organic Synthesis

Strong bases are indispensable in organic synthesis, playing a key role in the deprotonation of alcohols and phenols to form alkoxide and phenoxide ions. Their strength, meaning their ability to accept protons, determines their effectiveness in these reactions.

For example, sodium hydride, sodium hydroxide, and potassium tert-butoxide are commonly used bases capable of deprotonating alcohols and phenols due to their strong basic nature. The stronger the base, the more readily it can abstract a proton from the alcohol or phenol, enabling the subsequent steps in ether synthesis. It's important to match the strength of the base to the pKa of the starting alcohol or phenol to efficiently produce the alkoxide or phenoxide ion necessary for successful ether synthesis.