What is the Difference Between Synthesis and Retrosynthesis

The main difference between synthesis and retrosynthesis is that synthesis is the process of combining simple reactions to form an organic compound. But, retrosynthesis is the process of working backward from the target organic compound to devise a suitable route of synthesis, starting from a simple precursor molecule. Furthermore, synthesis is a chemical process done in a test tube, while retrosynthesis is some sort of planing done on a paper. 

Synthesis and retrosynthesis are two important processes in organic chemistry, allowing the construction of a particular organic compound, starting from simple precursor molecules through a series of chemical reactions. 

Key Areas Covered 

1. What is Synthesis
     – Definition, Process, Significance
2. What is Retrosynthesis
     – Definition, Process, Significance
3. What are the Similarities Between Synthesis and Retrosynthesis
     – Outline of Common Features
4. What is the Difference Between Synthesis and Retrosynthesis
     – Comparison of Key Differences

Key Terms 

Chemical Reactions, Organic Compounds, Retrosynthesis, Synthetic Intermediate, Synthesis, Synthon

What is Synthesis 

Synthesis is the process of constructing an organic compound chemically through a series of reactions. Generally, organic compounds are complexes that mainly contain covalent bonds. Also, the main significant feature of synthesis is that it starts from simple precursors, which leads to the formation of the target organic compound. Here, the precursor molecules can be either naturally or commercially available. Furthermore, there are two approaches to the total synthesis of an organic compound. They are the linear synthesis and convergent synthesis.

Figure 1: Alprostadil Synthesis

Generally, in the linear synthesis, several steps of chemical reactions are performed one after another. Therefore, it is only adequate for the synthesis of simple types of organic compounds. However, convergent synthesis involves individual preparation of several “pieces”  or key intermediates, which are then combined to form the desired product. Hence, it is preferable for the synthesis of more complex organic compounds. Here, synthetic intermediate refers to each chemical compound synthesized at the end of each step. Also, each chemical reaction is responsible for modifying the starting compound. 

What is Retrosynthesis 

Retrosynthesis is the deconstruction of the target organic compound, which is complex into its simple forms of precursors. However, it is done on a paper, not done chemically. Thereby, the main importance of retrosynthesis is that it helps to identify the route of synthesis of the target organic compound. Although it is a kind of paperwork, retrosynthesis is the reverse process of the synthesis. Therefore, it starts with the complex target compound and goes back to its simple precursors. Importantly, retrosynthesis permits the comparison of several routes of synthesis of a particular target compound in both a logical and straightforward manner. Basically, a synthon refers to a fragment of a compound that assists in the formation of a synthesis, derived from that target molecule. Also, synthetic equivalent refers to the corresponding commercially available form of a synthon.

Figure 2: Retrosynthetic Analysis of Phenylacetic Acid

Moreover, there are several strategies of retrosynthesis. They include functional group strategies, stereochemical strategies, structural-goal strategies, transform-based strategies, and topological strategies. Of these, functional group strategies manipulate functional groups of the organic compound, reducing its chemical complexity. Meanwhile, stereochemical strategies remove the chirality of the target in order to simplify it. However, structural-goal strategies direct the synthesis toward a desirable intermediate, greatly narrowing the focus of analysis. On the other hand, transform-based strategies reduce the molecular complexity of the target organic compound through the introduction of transformations. But, topological strategies identify key substructures by the disconnection of one or more key bonds. 

Similarities Between Synthesis and Retrosynthesis  

• Synthesis and retrosynthesis are two processes in the construction of a particular organic compound.  
• Both use simple precursor molecules in order to synthesize a complex organic compound through a series of chemical reactions in organic chemistry.  
• Here, the precursors can be either commercially available or natural molecules.  
• The construction of organic compounds is important for industrial purposes, especially in the pharmaceutical industry. 

Difference Between Synthesis and Retrosynthesis 

Definition 

Synthesis refers to a special branch of chemical synthesis and is concerned with the intentional construction of organic compounds, but retrosynthesis refers to a technique for searching a suitable route of synthesis in the planning of organic synthesis.  

Significance 

Synthesis is the process of combining simple reactions to form an organic compound, but retrosynthesis is the process of working backward from the target organic compound to devise a suitable route of synthesis starting from a simple precursor molecule.  

Direction 

Synthesis is the forward process, starting from precursors and ending from the target organic compound, but retrosynthesis is the reverse process, starting from the target organic compound and going back to its relevant precursors. 

Type of Process 

Synthesis is a chemical process done in a test tube, while retrosynthesis is some sort of planing done on a paper. 

Importance 

Synthesis is important for the chemical construction of an organic compound, while retrosynthesis is important for the planning of the synthesis of that particular organic compound starting from its precursors. 

Types 

The two approaches of synthesis are linear and convergent synthesis, while the strategies of retrosynthesis include the functional group strategies, stereochemical strategies, structural-goal strategies, transform-based strategies, and topological strategies.  

Conclusion 

Synthesis is a chemical process of constructing organic molecules by means of a series of chemical reactions. Generally, it starts from simple precursor molecules and ends up with the target organic compound, which is normally a complex. But, in contrast, retrosynthesis is the reverse process of synthesis, and it takes part in the deconstruction of the target organic compound in order to figure out its simple precursor molecules. However, it is a type of paperwork, which helps to find out a route of synthesis of the target organic compound. Hence, the main difference between synthesis and retrosynthesis is the direction and type of process. 

References:

1. “Organic Synthesis and Carbon-Carbon Bond Forming Reactions” Organic Synthesis and Carbon-Carbon Bond Forming Reactions, Available Here.
2. “A Simple Approach to Retrosynthesis in Organic Chemistry.” Retrosynthesis Organic Chemistry Tutorial, Available Here.

Image Courtesy:

1. “Alprostadil synthesis” By Nuklear – Own work (CC BY-SA 4.0) via Commons Wikimedia   
2. “Retrosynthetic analysis of phenylacetic acid” (Public Domain) via Commons Wikimedia