Practical Synthesis of Useful Substances Using Organocatalysts - Research Paper Example

Practical Synthesis of Useful Substances Using Organocatalysts I. Introduction The use of knowledge in organic chemistry has been beneficial developing chemical reactions that are industrially applied. In chemical reaction, catalysts serve to increase the rate of chemical reaction. Organocatalysts is a term that comes from two chemical terms organic and catalyst. It refers to a catalyst that comprises of organic compounds. Scientists argue that the ability to produce and recycle multiple reactions increases the efficacy of organocatalysts. This makes it a more efficient process, which uses fewer chemicals in the synthesis process, making it by a far greener and less toxic process. II. Background A. The concept of organocatalysis Acceleration of chemical processes through addition of substoichiometric quantity of organic compound refers to organocatalysis. In the last few years, interest in this field has increased because of selectivity and efficiency of many organocatalytic reactions, which have met standards of the required organic reactions. Observably, organocatalytic reactions are becoming popular in constructions of complex molecules. This recent development is because the process is less toxic compared to metallic catalysts. Predominant molecules used in the organocatalytic reaction are carbon, hydrogen, nitrogen, sulphur and phosphorous (McMurry, 2009). Organocatalysts usually display secondary characteristics, which would lead to enamine catalysis or iminium catalysis. The mechanism involved is covalent organocatalysis. High catalysts loading apply in covalent binding of substrates while non-covalent bonding requires low substrate loading. Knoevenagel Condensation applies regular achiral organocatalysts, which uses nitrogen as its basis. The current focus of organocatalysis is asymmetric organocatalysis, which involves the use of chiral catalysts. Scientific reactions indicate asymmetric catalysis occurs when organocatalyst is chiral as observed in aldol reactions (McMurry, 2009). Organocatalysts have the following advantages they are less sensitive to moisture or oxygen, readily available, less toxic, and inexpensive (Berkessel, 2006). These advantages make organocatalysts preferable in pharmaceutical processes. During the chemical reactions toxin produced usually influence usage of certain chemical process. Notably, organocatalysis has less impact to the environment. The condition for the reaction is relatively mild thus making organocatalysts preferable over metal catalysts. The following example illustrating Knoevenagel Condensation indicates that Piperdine forms iminium ion, which is reactive with carbonyl compound. Fig 1: Retrieved from http://www.organic-chemistry.org/topics/organocatalysis.shtm B. Definition of terms Catalyst is a chemical substance that increases the rate of a chemical reaction but does not change its chemical composition at the end of the chemical process. Organocatalyst are catalysts, which contain organic compounds. Enamine catalysts refers to a compound that forms when ketone or aldehyde react with secondary amine resulting into a loss of Water. Imine is a compound that contains carbon hydrogen double bond. Covalent bonding refers to a chemical bonding process where atoms share electrons. Covalent bonding occurs between non-metallic atoms. Chiral is a term used to describe a molecule that does not fit on its mirror image (Reetz & Joroch, 2008). Achiral refers to molecules that are identical or fit into their mirror image. Asymmetric organocatalysis refers to organic synthesis, which leads to introduction of desired element of chirality (Berkessel, 2006). This technology applies in pharmaceuticals since different enantiomers of molecule contain different biological components. Aldol reaction refers to a method that leads to formation of carbon-carbon bonds. Knoevenagel Condensation this refers to carbon acid compound condensation using aldehydes to produce unsaturated ? and ? compounds (Berkessel, 2006). III. The advent of organocatalysis has led to new opportunities for the manufacture of sustainable plastics. This is very important to world industrialization because the process allows recycling of useful substances. Polymer chemistry provides the basis of manufacture of plastics, which find a wide application in the industrial world. A. Organic catalysis for synthetic polymer chemistry A polymer is a large chemical molecule that comprises of repeated monomer. A monomer is the smallest unit that repeatedly bond together to form a polymer. In polymer science, polymerization refers to the degree of repletion of the basic units. Carbon molecules form the backbone of polymerization. The following illustration shows polymerization of propylene. Branching of chains discourages fitting of monomer close together thus leading to amorphous structure. In condensation polymer, the backbones contain non-carbon atoms as illustrated below. The use of unsymmetrical reactants reacts exclusively to form head to tail products. For instance, vinyl monomer reacts to form a product, which has head to tail in which substituent, appear on alternative atoms of carbon as illustrated below. –CH 2 –CHX–CH 2 –CHX–CH 2 –CHX–CH 2 –CHX– Ideally, polymer usually contains straight chains, which have short branches. Changing the structure of a polymer may lead to formation irregular structure. Manipulation of polymers leads to the formation of polymer which exhibit different structure. B. Ring opening polymerization In ring opening polymerization, the terminal of a polymer forms a reactive center where cyclic monomer bond through ionic propagation to form a large polymer. Treatment of cyclic polymer leads to cleavage of ring and eventual polymerization (Reetz & Joroch 2008). Usually, the reactive center influence polymerization i.e. cationic ring opening occurs when propagating chain is carbocation, polymerization that occurs. When a reactive center is an anion, the reaction that follows leads to formation of anion ring opening. Olefin metathesis leads to formation of ring opening polymerization, which does not use anion or cationic propagation. The illustration below shows the structure ring-opening polymerization. Fig 2: Retrieved from http://onlinelibrary.wiley.com/doi/10.1002/anie.201107239/abstract C. Applications using organic catalysts rather than the most active metal-based catalysts Organic catalysts find application in the following areas pharmaceutical and industrial manufacture and recycle of plastic. Example of polymers manufactured through open-ring polymerization includes polycaprolactame, polylauroamide, polycaprolactone, polythene oxide, polyproplyne oxide, and polytetrahydrofuran. Food process industry use catalysis process of hydrogenation to preserve or process liquid oil to fat. Manufacture of chemical also uses the organocatalysts to manufacture bioactive compounds. In petroleum refining, organocatalysts apply as reactants that leads to processing of petroleum. Another application is energy processing where harmful by products from automobile break down to form carbon dioxide and nitrogen, which are not harmful to the environment (McMurry, 2009). IV. Organocatalyst for direct aldol reactions of aldehydes and ketones Two different enantiometric products (aldehydes and ketones) are used to achieve asymmetric synthesis by using a single organocatalyst having (or lacking) chiral organic acid additives. A. Chirality and enantioselectivity of certain organocatalysts In enantioselective hydrogenation, hydride donor or molecular hydrogen combined with a chiral metal catalyst system is dominating as the preeminent plan for asymmetric catalysis in the chemical community. Indeed, it is intriguing to note that most of the current C-H stereogenic centers were created via organometallic catalysis (List, 2010). This is attributed to the numerous and continuous biochemical processes that form hydrogen-bearing stereo-centers existing in biological sequences controlled by hydride reduction cofactors and enzymes. 1. Definition of terms Aldehydes and ketones are compounds that contain a carbon-oxygen double bond (carbonyl group). These compounds are simple since they do not contain other reactive groups like -CI or –OH attached to the carbon atom in the carbon-oxygen double bond, particularly common in carboxylic acids having the –COOH attachment (Reetz, List, and Jaroch, 2008). The carbonyl group in aldehydes has a hydrogen atom attached together with another hydrogen atom or a hydrocarbon group containing either a benzene ring or an alkyl group. Examples of aldehydes include ethanal, methanal, and 2-methylbutanal among others. Aldehydes difference with ketone is that they have the carbonyl group has a hydrogen atom attachment, making ladehydes easy to oxidize. Enantioselectivity of organocatalysts refers to the degree to which a given a chiral product’s enantiomer is produced preferentially in a chemical reaction (Dalko, 2007). Chirality is the level of handedness displayed by a molecule. An aldol reaction is a condensation reaction that involves aldehydes resulting in an aldol. Fig 3: Aldol reaction. Retrieved from http://onlinelibrary.wiley.com/doi/10.1002/anie.201107239/abstract 2. Applications The main area of application of chirality and enantioselectivity of organocatalysts is asymmetric synthesis and other photochemical reactions that produce pharmaceutically important products having excellent enantioselectivities and high yields (List, 2010). B. S- proline as Organocatalyst for aldol reactions Asymmetric aldol reaction is difficult to achieve in water, but presence of polar solvents like dimethyl sulfoxide (DMSO) improve the efficiency of reaction. Presence of a proline-surfactant (S-proline) with an enamine intermediate in aldol reactions improves the enantioselectivities (Dalko, 2007). 1. Aldol reactions of aldehydes donors Aldol reactions generally occur through nucleophilic addition of enolate ion from donor molecules to the acceptor’s molecule carbonyl group (Dalko, 2007). Acetaldehyde reacts with another acetaldehyde molecule in a basic solution (NaOH or NaOEt) to produce a ?-hydroxy aldehydes result, or aldol. Below is the general reaction. Fig 4: Aldol reactions of aldehydes donors. Retrieved from http://www.highlands.edu/academics/divisions/scipe/chemistry/Site/Chem2402Klect_files/Lecture%20Notes%20Chapter%2023.pdf 2. Aldol reactions of ketone donors Various organocatalysts for asymmetric aldol reactions of ketones having ?-keto acids have designs based on molecular recognition and preparation from aminopyridines and proline. The best catalyst was organic molecule 8e from 6-methyl-2-amino pyridine and proline, achieving a 98%ee for direct aldol reaction of ketone donors like 2-butanone and acetone with a range of ?-keto acids and reaction of different acyclic aliphat ketones having 3-(2-nitrophenyl)-2-oxopropanoic acid (Dalko, 2007). Additionally, aldol adducts may convert to 2-hydro-y-butyrolactones by diastereoselective lactonization and reduction. Fig 5: Aldol reactions of ketone donors . Retrieved from http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/joceah/2007/joceah.2007.72.issue-26/jo701868t/production/images/medium/jo701868tn00001.gif 3. Intramolecular aldol reactions Intermolecular aldol reactions form an important pathway for cyclic compounds synthesis, but only five or six-member rings may be achieved. Additionally, the two-carbonyl components of the starting product can react as nucleophilic enolate or electrophilic carbonyl component (Dalko, 2007). Moreover, ketones carbonyl components may form two different enolates, thus there is possibility of having various products. C. Enamine catalysis Enamine catalysis is an essential strategy in the use of carbanion equivalents and for the catalytic generation. The foundation of this strategy is the catalytic and reversible generation of enamines from carbonyl and amines products (Reetz, List, and Jaroch, 2008). The formation of enamines is facilitated by the rapid increase of C-H-acidity when carbonyl compounds conversion to iminium ion takes place. The enamine generated then passes through addition reactions with different electrophiles through substitution reaction or nucleophilic addition (Dalko, 2007). Hydrolysis with generated water furnishes the resulting iminium ion. D. L-proline as an asymmetric Organocatalyst L-proline contains an isoster of type (S)-(–)-5-(2-Pyrrolidinyl)-1H-tetrazole, similar to pKa, has greater anticipated reactivity and solubility in lipophilic organic solvents. Their main applications include synthesis of organocatalytic application, proving its usefulness in various reactions. 1. Chiral molecule A chiral molecule is one that has non-superposible mirror image, or lacks symmetry of its internal plane. The cause of chirality in molecules is often asymmetric carbon atom presence (Reetz, List, and Jaroch, 2008). Their opposite, achiral, refer to molecules that have similar identity to their mirror image. They also have characteristics of optical activity. Fig 6: Chiral molecule. Retrieved from http://physics.unl.edu/~tgay/content/ChiralM.html 2. Enantioselectivity and catalyst for intermolecular reactions Excellent and good yields enantioselectivities result from cis-fused triquinane derivatives. These derivatives result from elements like Diphenylprolinol silyl that is an effective organocatalyst in the promotion of catalytic, asymmetric, intermolecular [6+2] cycloaddition fulvenes reaction (List, 2010). V. Recycling procedures A. Recovery of catalyst Organocatalysts tagged with Fluorous are used by various groups in removal, recovery, and reuse of important catalyst in post-reaction mixtures. An example is using sulfonamide derivate (L-phenylalamine) in asymmetric an aldol reaction running in brine. Fig 7: Recovery of catalyst Retrieved from http://www.fluorous.com/journal/?p=1386 B. Recycle catalyst The best catalytic asymmetric conjugate strategy involves combining ?, ?-unsaturated aldehydes to nitroalkanes in an aqueous environment through using water-soluble organocatalysts like benzoic acid and diarylprolinol silyl ether. The result adduct has an enantioselectivity of 95% ee (List, 2010). The catalyst is recyclable at least five times, with slight reduction in selectivity and activity. C. Environmental benefits Organocatalysis contributes to green chemistry, as it does not require metal-based catalysis. Simple organic acids are used as catalysts to modify cellulose in water on a large scale. Chiral organocatalysts open avenues for asymmetric catalysis, as is the case with proline in aldol reaction. VI. Conclusion In essence, organocatalysis is the acceleration or speeding up of a chemical step using molecules that do not contain metals, such as proline, thiazolium salts, Cinchona alkaloids, DMAP, among others (List, 2010). It has had an enormous impact on chemistry synthesis over the past decades. Organocatalysis represents a very diverse and powerful field in chemistry analysis, but many biochemist experts have not ventured in it. It is also a very effective complementary to metal-catalysis, as its asymmetric catalysis do not harm the environment. The chemistry field has high environmental sustainability and economic potential. Nonetheless, it has some drawbacks, including variability of yields, the need asymmetric synthesis of syn-aldol adducts. Moreover, catalysts are not general, and may become more complex than (S)-Pro. The reactions may also require tailoring after organocatalytic process. Reference List Berkessel, A. et.al . Asymmetric Organocatalysis: From Biomimetic Concepts to Applications in Asymmetric Synthesis; John Willy & Sons: New Jersey, 2006. Dalko, P. O. Enantioselective Organocatalysis; Wiley-VCH Verlag GnbH & Co: Weinheim, 2007. List, B. Asymmetric Organocatalysis; Springer –Verlag Berlin Heidelberg: Berlin, 2010. McMurry, J. Organic Chemistry: With Biological Applications; Cengage Learning: New York, 2009. Reetz, M.; List, B.; Jaroch, S. Organocatalysis; Springer –Verlag Berlin Heidelberg: Berlin, 2008. Read More