User:Leafsfan3/Organic synthesis

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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 are many different types of synthetic routes including Total Synthesis, Stereoselective Synthesis, and Automated Synthesis. Also important to organic synthesis are the synthetic techniques, methodology, and characterization techniques used to analyze organic products.

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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 chemistry was reserved for large-scale industrial chemistry but has recently transitioned to bench-scale chemistry to improve the efficiency of reactions beyond industry(1).

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(2).

Automated chemistry and the Automated synthesizers used, demonstrate a potential direction for synthetic chemistry in the future.

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) is used.

Liquid-Liquid Extraction

Separation02

Liquid-liquid extraction harnesses the density and polarity of the product and solvents used during separation(6). 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 two layers to form within the flask, one layer containing the 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 side-material layer can be removed.

Heated Reactions and Reflux Condensors

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 potentially reduces 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 against gravity. This flow of water cools any escaping substrate and condenses it back into the reaction flask to continue reacting(3) and ensure that all product is contained. The use of reflux condensers is important in multiple steps within organic syntheses including initial reaction/reflux, and recrystallization.

When being used for reaching reflux, 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(3).

Reflux labled

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(5).

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.

FilterFunnelApparatus

Vacuum filtration uses suction to pull liquid through a Buchner funnel equipped with filter paper, which catches the desired solid product(4). This process removes any unwanted solution in the reaction mixture, trapping it in the filtration flask and leaving only the desired product.

Liquid products can also be separated from solids by using gravity filtration(4). 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(4). This method allows for the product to be separated from other reaction components by the force of gravity, instead of a vacuum.

Cold Filtration

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), Mass spectroscopy, Fourier-Transform Infrared Spectroscopy (FTIR), and melting point analysis. Each of these techniques allow for a chemist to obtain structural information about a newly synthesized organic compound. Depending on the nature of the experiment, the characterization method used can vary.

Relevance of Organic Synthesis

Organic synthesis is an important chemical process that is integral to many scientific fields like the medical and pharmaceutical industry. These organic processes allow for the industrial-scale creation of pharmaceutical products that are relied on daily. An example of such a synthesis is Ibuprofen. Ibuprofen can be synthesized from a series of reactions including: reduction, acidification, formation of a Grignard reagent, and carboxylation(7).

Synthesis of Ibuprofen by Kjonass et. al

Specifically, p-isobutylacetophenone (starting material) is reduced with Sodium Borohydride (NaBH4) to form an alcohol functional group. The resulting intermediate is then acidified with HCL to create a chlorine group which is then reacted with Magnesium turnings to form a Grignard Reagent(7). The newly formed Grignard is then carboxylated to form the desired product, Ibuprofen. Without organic synthesis, the production of Ibuprofen and many other important drugs would not be possible.

Line Edits to be made to the original article:

• Revise wording and remove unnecessary filler
• Revise the statement claiming that "Organic molecules are often more complex than inorganic compounds". This is not true, and creates a misconception about chemistry as a whole.
• Find additional sources for claims that are made without a literature-backing
• Add hyperlinks to words that should have them
• Remove stereoselective synthesis paragraph. We feel this is too specific for such a broadly defined wikipedia article, and could be adequately described with one or two sentences
• Similarly, the synthetic design portion can be greatly reduced. We feel that simply defining retro synthetic analysis is enough for this article.
• Additionally, the methodology section will be revised for content as some of it is too lengthy.

References

1. A. Kirschning (Editor): Chemistry in flow systems and Chemistry in flow systems II Thematic Series in the Open Access Beilstein Journal of Organic Chemistry.
2. Collins, N.; Stout, D.; Lim, J.-P.; Malerich, J. P.; White, J. D.; Madrid, P. B.; Latendresse, M.; Krieger, D.; Szeto, J.; Vu, V.-A.; Rucker, K.; Deleo, M.; Gorfu, Y.; Krummenacker, M.; Hokama, L. A.; Karp, P.; Mallya, S. Fully Automated Chemical Synthesis: Toward the Universal Synthesizer. Organic Process Research & Development 2020, 24 (10), 2064–2077. https://doi.org/10.1021/acs.oprd.0c00143.
3. Nichols, L. Reflux. Chemistry LibreTexts. https://chem.libretexts.org/Bookshelves/Organic_Chemistry/Organic_Chemistry_Lab_Techniques_(Nichols)/01%3A_General_Techniques/1.04%3A_Heating_and_Cooling_Methods/1.4K%3A_Reflux.
4. Nichols, L. 1.5A: Overview of Methods. Chemistry LibreTexts. https://chem.libretexts.org/Bookshelves/Organic_Chemistry/Organic_Chemistry_Lab_Techniques_(Nichols)/01%3A_General_Techniques/1.05%3A_Filtering_Methods/1.5A%3A_Overview_of_Methods.
5. ‌Barich, A. Recrystallization. Chemistry LibreTexts. https://chem.libretexts.org/Bookshelves/Physical_and_Theoretical_Chemistry_Textbook_Maps/Supplemental_Modules_(Physical_and_Theoretical_Chemistry)/Physical_Properties_of_Matter/Solutions_and_Mixtures/Case_Studies/RECRYSTALLIZATION.
6. Nichols, L. 4.2: Overview of Extraction. Chemistry LibreTexts. https://chem.libretexts.org/Bookshelves/Organic_Chemistry/Organic_Chemistry_Lab_Techniques_(Nichols)/04%3A_Extraction/4.02%3A_Overview_of_Extraction.
7. Kjonaas, R. A.; Williams, P. E.; Counce, D. A.; Crawley, L. R. Synthesis of Ibuprofen in the Introductory Organic Laboratory. Journal of Chemical Education 2011, 88 (6), 825–828. DOI:10.1021/ed100892p.