Question

It is thought that the first amino acids were synthesized from formaldehyde, hydrogen cyanide, ammonia and water in the primitive atmosphere. A possible synthesis involves a series of nucleophilic attacks and proton transfers. Propose a mechanism for the synthesis of glycine using the above mentioned compounds.

Short answer

The synthesis of glycine can be proposed using formaldehyde, hydrogen cyanide, ammonia, and water through a series of nucleophilic attacks and proton transfers. Initially, hydrogen cyanide reacts with formaldehyde to form a cyanohydrin. A proton transfer occurs, followed by nucleophilic addition of ammonia, forming an amino nitrile intermediate. Finally, hydrolysis of the nitrile group results in the formation of glycine.

Step-by-step solution

Identify the nucleophiles and electrophiles in the reactants

To begin the synthesis, we need to identify the nucleophilic and electrophilic centers of the reactants. Formaldehyde (H2CO) contains a polar carbonyl group with a partially positive carbon atom, making it electrophilic. Hydrogen cyanide (HCN) has a polar C≡N triple bond with a negative charge on the carbon atom, making it nucleophilic. Ammonia (NH3) has a lone pair on the nitrogen atom, making it nucleophilic as well. Water (H2O), which will be the solvent for the reaction, acts as a source of protons (H+) and a proton acceptor (OH-) for proton transfers.

Nucleophilic addition of HCN to H2CO

The first step in the synthesis is the nucleophilic addition of hydrogen cyanide (HCN) to formaldehyde (H2CO). The nucleophilic carbon atom of HCN attacks the electrophilic carbon atom of the carbonyl group in H2CO, forming a new C-C bond. The negative charge on the oxygen is now neutralized by a proton transfer from HCN to the oxygen atom, resulting in the formation of an imine and releasing a hydroxide ion (OH-). The intermediate product will be a cyanohydrin with the formula OHC-CH2-CN.

Proton transfer and nucleophilic addition of ammonia

The next step involves a proton transfer from the hydroxyl group of cyanohydrin to the water molecule, resulting in the formation of an oxonium ion and a hydroxide ion (OH-). The oxonium ion can now react with ammonia (NH3) through a nucleophilic attack. The nitrogen of ammonia attacks the electrophilic carbon of the oxonium ion, forming a nitrogen-carbon bond and breaking the carbon-oxygen bond.

Proton transfer to form the amino nitrile intermediate

The oxygen atom with the negative charge acquires a proton from water, generating a hydroxide ion again and stabilizing the intermediate. At this stage, we have an amino nitrile intermediate with the formula NH2-CH2-CN.

Hydrolysis of the nitrile group to form glycine

The final step in the synthesis of glycine involves the hydrolysis of the nitrile group in the amino nitrile intermediate. The hydroxide ion attacks the carbon of the nitrile group, resulting in the formation of a new carbon-oxygen bond. This is followed by a proton transfer from water to the nitrogen atom, yielding cyanic acid, which further hydrolyses to produce CO2 and another hydroxide ion. The hydroxide ion then removes a proton from the ammonium ion, resulting in the formation of glycine NH2-CH2-COOH. The proposed mechanism used formaldehyde, hydrogen cyanide, ammonia, and water to synthesize glycine through several nucleophilic attacks and proton transfers.

Key concepts

Nucleophilic Substitution

Nucleophilic substitution is an essential reaction type in organic chemistry. It involves the replacement of an atom or a group by a nucleophile. This process is pivotal when discussing the synthesis of glycine from simpler molecules.
In the context of glycine synthesis, the reactants exhibit distinct nucleophilic and electrophilic characteristics:

• Formaldehyde ( H_2CO")): Contains an electrophilic center at the carbon in the carbonyl group due to electronic polarization.
• Hydrogen cyanide ( HCN": A triple bond polarizes the carbon, providing nucleophilic properties to react with formaldehyde.
• Ammonia ( NH_3"): The lone pair on nitrogen provides nucleophilic behavior, crucial for subsequent reactions.
• Water ( H_2O"): Serves dual roles, both as a proton donor and acceptor, facilitating essential proton transfers.

Understanding these roles helps elucidate how nucleophilic attacks drive the conversion of starting materials into intermediate and final products in the amino acid synthesis.

Amino Acid Formation

Amino acid formation, particularly for glycine, from primitive atmospheric components is a fascinating chemical journey. The process exemplifies how life's building blocks could have arisen from simple molecules through a series of chemical reactions.
The synthesis pathway described consists of multiple steps where key intermediates are formed:

• Initially, hydrogen cyanide adds nucleophilically to formaldehyde, forming a cyanohydrin.
• The introduction of ammonia leads to a transformation into an amino nitrile intermediate.
• Hydrolysis of the nitrile group concludes the process, resulting in glycine.

This sequence of transformations illustrates nature’s propensity for forming complex structures from basic origins, a crucial understanding in prebiotic chemistry.

Chemical Mechanism Steps

Exploring the detailed mechanism of glycine synthesis involves appreciating each step in the structured pathway. Initially, nucleophilic addition plays a critical role where HCN" attacks H_2CO". This is followed by proton transfers enabling the stabilization of intermediate structures.
Each subsequent step enables necessary transformations:

• Formation of the cyanohydrin, which includes a proton transfer from HCN" to neutralize the negative oxygen charge.
• Nucleophilic addition of ammonia to the oxonium ion, which aids breaking and forming new bonds.
• Hydrolysis of the nitrile group finally restructures molecules into the amino acid. This involves attacking by hydroxide ions and multiple proton transfers, ultimately forming glycine.

Grasping these mechanisms reveals the importance of each step and the roles these molecules play towards forming amino acids like glycine.