Organic synthesis
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,[1] stereoselective synthesis,[2] automated synthesis,[3] and many more. Additionally, in understanding organic synthesis it is necessary to be familiar with the methodology, techniques, and applications of the subject.
Total synthesis
A total synthesis refers to the complete
Methodology and applications
Before beginning any organic synthesis, it is important to understand the
Synthetic techniques
Organic Synthesis requires many steps to separate and purify products. 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.[15][16]
Liquid–liquid extraction
Heated reactions and reflux condensers
Many reactions require heat to increase reaction speed.[18] 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 calibrated 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[19] 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.[19]
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.[20]
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.
Liquid products can also be separated from solids by using gravity filtration.[15] 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.[15] This method allows for the product to be separated from other reaction components by the force of gravity, instead of a vacuum.
Stereoselective synthesis
Most complex
As chemistry has developed methods of stereoselective
Using techniques developed by
Synthesis design
Many synthetic procedures are developed from a
Automated organic synthesis
A recent development within organic synthesis is automated synthesis. To conduct organic synthesis without human involvement, researchers are adapting existing synthetic methods and techniques to create entirely automated synthetic processes. This type of synthesis is advantageous as synthetic automation can increase yield with continual "flowing" reactions. In flow chemistry, substrates are continually fed into the reaction to produce a higher yield. Previously, this type of reaction was reserved for large-scale industrial chemistry but has recently transitioned to bench-scale chemistry to improve the efficiency of reactions on a smaller scale.[3]
Currently integrating automated synthesis into their work is SRI International, a nonprofit research institute. Recently SRI International has developed Autosyn, an automated multi-step chemical synthesizer that can synthesize many FDA-approved small molecule drugs. This synthesizer demonstrates the versatility of substrates and the capacity to potentially expand the type of research conducted on novel drug molecules without human intervention.[29]
Automated chemistry and the automated synthesizers used demonstrate a potential direction for synthetic chemistry in the future.
Characterization
Necessary to organic synthesis is characterization. Characterization refers to the measurement of chemical and physical properties of a given compound, and comes in many forms. Examples of common characterization methods include: nuclear magnetic resonance (NMR),[30] mass spectrometry,[31] Fourier-transform infrared spectroscopy (FTIR),[32] and melting point analysis.[33] Each of these techniques allow for a chemist to obtain structural information about a newly synthesized organic compound. Depending on the nature of the product, the characterization method used can vary.
Relevance
Organic synthesis is an important chemical process that is integral to many scientific fields. Examples of fields beyond chemistry that require organic synthesis include the
In the synthesis of Ibuprofen proposed by Kjonass et al., p-isobutylacetophenone, the starting material, is reduced with sodium borohydride (NaBH4) to form an alcohol functional group. The resulting intermediate is acidified with HCl to create a chlorine group. The chlorine group is then reacted with magnesium turnings to form a Grignard reagent.[34] This Grignard is carboxylated and the resulting product is worked up to synthesize ibuprofen.
This synthetic route is just one of many medically and industrially relevant reactions that have been created, and continued to be used.
See also
- Automated synthesis
- Electrosynthesis
- Methods in Organic Synthesis(journal)
- Organic Syntheses (journal)
References
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- ^ "13.2: Solutions- Homogeneous Mixtures". Chemistry LibreTexts. 2020-02-25. Retrieved 2023-12-08.
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Further reading
- ISBN 978-0471115946.