Question

Starting with ethylene oxide and methy 1 iodide as the only organic materials, suggest a synthesis of alanine, \(\mathrm{CH}_{3} \mathrm{CH}\left(\mathrm{NH}_{2}\right) \mathrm{CO}_{2} \mathrm{H}\), an important amino acid.

Short answer

To synthesize alanine starting with ethylene oxide and methyl iodide, follow these steps: 1. React ethylene oxide with methyl iodide: \( CH2-O-CH2 + CH3I \rightarrow (CH2-O-CH2-CH3)^+ \) 2. Deprotonate the alpha proton: \((CH3)_{2}CH-\overset{_-}{O} -> CH2=CH-\overset{_-}{O}\) 3. Perform a nucleophilic attack with cyanide: \( CH2=CH-\overset{_-}{O} + HCN \rightarrow CH2=CH-CN \) 4. Hydrolyze the nitrile group to form a carboxylic acid: \( CH2=CH-CN + H2O + H2SO4 \rightarrow CH2=CH-COOH + NH3\) 5. React with ammonia to form alanine: \( CH_{2}= CHCOOH+NH_{3} \rightarrow CH_{3} CH(NH_{2}) CO_{2}H \)

Step-by-step solution

Ethylene oxide reaction with methyl iodide

First, we need to open the ethylene oxide ring. This can be done by reacting ethylene oxide with methyl iodide in the presence of a base. Reaction: \[ CH2-O-CH2 + CH3I \rightarrow (CH2-O-CH2-CH3)^+\]

Deprotonation

Next, we need to deprotonate the proton in the alpha-position to form a carbanion. Reaction: \[(CH3)_{2}CH-\overset{_-}{O} -> CH2=CH-\overset{_-}{O} \]

Cyanide nucleophilic attack

For the next step, allow the carbanion to react with hydrogen cyanide (HCN). The negatively charged oxygen will attack the carbon in HCN, resulting in a nitrile group formation. Reaction: \[ CH2=CH-\overset{_-}{O} + HCN \rightarrow CH2=CH-CN \]

Nitrile hydrolysis to carboxylic acid

The nitrile group can be hydrolyzed to a carboxylic acid by treating it with an aqueous solution of a strong acid, such as sulfuric acid. Reaction: \[ CH2=CH-CN + H2O + H2SO4 \rightarrow CH2=CH-COOH + NH3\]

Addition of ammonia to form the final product

Finally, react the obtained compound with ammonia (NH3). The carboxylic group converts into an amide group, forming alanine as the final product. Reaction: \[ CH_{2}= CHCOOH+NH_{3} \rightarrow CH_{3} CH(NH_{2}) CO_{2}H \] In summary, these are the main steps for the synthesis of alanine starting with ethylene oxide and methyl iodide: 1. Reaction of ethylene oxide with methyl iodide. 2. Deprotonation of the alpha proton. 3. Nucleophilic attack of cyanide on the carbanion. 4. Hydrolysis of the nitrile group to form the carboxylic acid. 5. Reaction with ammonia to form alanine.

Key concepts

Ethylene Oxide

Ethylene oxide is a cyclic ether and an extremely important chemical used as a starting material in producing various compounds, including the synthesis of amino acids like alanine. Its three-membered ring structure is characterized by high ring strain, which makes it highly reactive and susceptible to ring-opening reactions. In the context of alanine synthesis, ethylene oxide reacts with methyl iodide. This initial step creates a more reactive intermediate that can further participate in downstream chemical transformations. The ring-opening of ethylene oxide is facilitated by a nucleophile in subsequent nucleophilic attack steps.
A crucial comment for learners is to understand that the high reactivity of ethylene oxide’s strained ring makes it an ideal candidate for initiating the synthetic process. Moreover, recognizing that ethylene oxide can react with a wide range of nucleophiles, such as methyl iodide, lays the foundation for understanding its behavior in complex organic synthesis scenarios.

Nucleophilic Attack

Nucleophilic attack is a fundamental type of chemical reaction wherein a nucleophile, an electron-rich molecule or ion, targets an electron-deficient site or electrophile. This process is essential in the formation of many organic compounds, such as during the synthesis of the amino acid alanine. In the provided exercise, the formation of a carbanion through deprotonation sets the stage for a nucleophilic attack by the negatively charged oxygen on hydrogen cyanide (HCN).
Understanding this concept is crucial as it directs how we can form new bonds in organic molecules. The nucleophile in question must have a pair of electrons it can donate, and the electrophile it targets should be willing to accept those electrons. The cyanide anion's attack results in a nitrile group, pivotal in converting a simple carbon chain into a molecule with the potential to be an amino acid. Explaining nucleophilic attacks with real-life examples can greatly enhance the learning experience for students.

Nitrile Hydrolysis

Nitrile hydrolysis is a chemical transformation that converts nitrile groups to carboxylic acids or their derivatives, such as amides. This conversion is significant in synthesizing amino acids from simpler starting materials. In alanine synthesis, nitrile hydrolysis is accomplished by treating the nitrile group with an aqueous solution of a strong acid. The reaction of the nitrile with water and sulfuric acid leads to the formation of a carboxylic acid and ammonia.
By grasping the nitrile hydrolysis mechanism, students can understand how carboxylic acids, vital functional groups in biochemistry, are introduced into organic molecules. The process of hydrolysis underscores the importance of water and acid catalysis in modifying molecular structures and paves the way for the final step of amino acid synthesis. Describing the process step-by-step with possible intermediate structures helps solidify the learning of nitrile hydrolysis.

Amino Acid Synthesis

Amino acid synthesis involves creating amino acids, the building blocks of proteins, from simpler organic compounds through a series of chemical reactions. The final steps often involve the incorporation of an amino group (-NH2) into the molecule. In the context of alanine synthesis, after the nitrile hydrolysis, the resulting carboxylic acid is reacted with ammonia. This allows the carboxylic group to convert into an amide, ultimately resulting in the production of alanine.
A key component for learners is to recognize that amino acid synthesis is a delicate orchestration of reactions that integrate both amino and carboxyl groups into a single molecule. Linking this process to the body's method of synthesizing amino acids can provide a real-world application that may help students understand and remember the steps involved in laboratory synthesis. It demonstrates the direct application of organic synthesis in biology and biochemistry.