Organic synthesis is a branch of chemical synthesis concerned with the construction of organic compounds. Organic compounds are molecules consisting of combinations of covalently-linked hydrogen, carbon, oxygen, and nitrogen atoms. Within the general subject of organic synthesis, there are many different types of synthetic routes that can be completed including total synthesis, stereoselective synthesis, automated synthesis, and many more.
Total synthesis
A total synthesis refers to the complete chemical synthesis of molecules from simple, natural precursors. Total synthesis is accomplished either via a linear or convergent approach. In a linear synthesis—often adequate for simple structures—several steps are performed sequentially until the molecule is complete; the chemical compounds made in each step are called synthetic intermediates. Most often, each step in a synthesis is a separate reaction taking place to modify the starting materials. For more complex molecules, a convergent synthetic approach may be better suited. This type of reaction scheme involves the individual preparations of several key intermediates, which are then combined to form the desired product. Robert Burns Woodward, who received the 1965 Nobel Prize for Chemistry for several total syntheses including his synthesis of strychnine, is regarded as the grandfather of modern organic synthesis. Some latter-day examples of syntheses include Wender's, Holton's, Nicolaou's, and Danishefsky's total syntheses of the anti-cancer drug paclitaxel (trade name Taxol).
Methodology and applications Understanding the chemical reactions, reagents, and conditions required in each step to guarantee successful product yield is essential for organic synthesis. When determining optimal reaction conditions for a given synthesis, the goal is to produce an adequate yield of pure product with as few steps as possible. When deciding conditions for a reaction, the literature can offer examples of previous reaction conditions that can be repeated, or a new synthetic route can be developed and tested. For practical, industrial applications additional reaction conditions must be considered to include the safety of both the researchers and the environment, as well as product purity.
Synthetic techniques Organic synthesis may require many steps to separate and purify products after performing one or more chemical reactions. Depending on the chemical state of the product to be isolated, different techniques are required. For liquid products, a very common separation technique is liquid–liquid extraction and for solid products, filtration (gravity or vacuum) can be used.
Liquid–liquid extraction
Liquid–liquid extraction uses the density and polarity of the product and solvents to perform a separation. Based on the concept of "like-dissolves-like", non-polar compounds are more soluble in non-polar solvents, and polar compounds are more soluble in polar solvents. By using this concept, the relative solubility of compounds can be exploited by adding immiscible solvents into the same flask and separating the product into the solvent with the most similar polarity. Solvent miscibility is of major importance as it allows for the formation of two layers in the flask, one layer containing the side reaction material and one containing the product. As a result of the differing densities of the layers, the product-containing layer can be isolated and the other layer can be removed.
Heated reactions and reflux condensers
Many reactions require heat to increase reaction speed. However, in many situations increased heat can cause the solvent to boil uncontrollably which negatively affects the reaction, and can potentially reduce product yield. To address this issue, reflux condensers can be fitted to reaction glassware. Reflux condensers are specially designed pieces of glassware that possess two inlets for water to run in and out through the glass against gravity. This flow of water cools any escaping substrate and condenses it back into the reaction flask to continue reacting and ensure that all product is contained. The use of reflux condensers is an important technique within organic syntheses and is utilized in reflux steps, as well as recrystallization steps. When being used for refluxing a solution, reflux condensers are fitted and closely observed. Reflux occurs when condensation can be seen dripping back into the reaction flask from the reflux condenser; 1 drop every second or few seconds. For recrystallization, the product-containing solution is equipped with a condenser and brought to reflux again. Reflux is complete when the product-containing solution is clear. Once clear, the reaction is taken off heat and allowed to cool which will cause the product to re-precipitate, yielding a purer product.
Gravity and vacuum filtration
Solid products can be separated from a reaction mixture using filtration techniques. To obtain solid products a vacuum filtration apparatus can be used. Vacuum filtration uses suction to pull liquid through a Büchner funnel equipped with filter paper, which catches the desired solid product. This process removes any unwanted solution in the reaction mixture by pulling it into the filtration flask and leaving the desired product to collect on the filter paper.
Liquid products can also be separated from solids by using gravity filtration. In this separatory method, filter paper is folded into a funnel and placed on top of a reaction flask. The reaction mixture is then poured through the filter paper, at a rate such that the total volume of liquid in the funnel does not exceed the volume of the funnel. This method allows for the product to be separated from other reaction components by the force of gravity, instead of a vacuum.
Stereoselective synthesis
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