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Sustainable methodologies for synthesis of small organic molecules using micellar catalysis
Deborah Sam Ogulu ; University of Louisville,2024,4274.
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Abstract: Organic synthesis is a critical process in the creation of small molecule pharmaceuticals and agrochemicals. However, most methods for synthesizing these small molecules rely on toxic organic solvents as the reaction medium which account for approximately 80% of pharmaceutical waste. Moreover, many catalytic reactions require expensive endangered precious metals like palladium and costly metals. This dissertation presents research that aims to develop sustainable, eco-friendly reaction conditions to address these issues. Chapter 1 provides an overview of green and sustainable chemistry and chemistry in water. It explains what sustainability entails and the drive towards greener synthetic methods. Also included is the introduction to the concept of chemistry in water, the different types of roles of water in chemistry, and the development of micellar catalysis – including its evolution, applications, current challenges, and future directions. Chapter 2 discusses the development of a ligand-free bimetallic nanocatalyst for the hydrogenation of unsaturated enones. This ligand-free nanocatalyst was prepared from nickel and ppm loading of palladium and was stabilized by harnessing the structural features of the amphiphile, PS-750-M. The physical properties of the nanoparticles were evaluated and thoroughly characterized using different analytical techniques like HRTEM, XPS, and TGA. Chapter 3 describes the application of a copper catalyst in the hydroboration of unsymmetrical internal alkynes with high regioselectivity under aqueous micellar conditions. The methodology was amenable to internal alkynes with diverse functional groups and provides a unique route to access β selective alkenyl boronates. Chapter 4 showcases the development of a protocol towards coupling of aryl boronic acids and primary amines under aqueous micellar conditions using an inexpensive nickel catalyst and oxygen balloon. The developed methodology provides another way to access amines under more sustainable reaction conditions. Chapter 5 describes the use of ppm palladium and copper catalysts immobilized on silica for the catalytic dehydration of amides to nitriles. The protocol employs acetonitrile as the additive and the reaction is performed using aqueous PS-750-M as the reaction medium.
CAS No. : | 1120-90-7 | MDL No. : | MFCD00023553 |
Formula : | C5H4IN | Boiling Point : | No data available |
Linear Structure Formula : | - | InChI Key : | XDELKSRGBLWMBA-UHFFFAOYSA-N |
M.W : | 205.00 | Pubchem ID : | 70714 |
Synonyms : |
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Signal Word: | Warning | Class: | |
Precautionary Statements: | P261-P305+P351+P338 | UN#: | |
Hazard Statements: | H315-H319-H335 | Packing Group: | |
GHS Pictogram: |
* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
54% | With palladium diacetate; In 1-methyl-pyrrolidin-2-one; at 20 - 140℃; for 24.0h;Inert atmosphere; | General procedure: An oven-dried Schlenk-tube (10?mL) was charged with Pd source (1?mol?percent), and ethyl potassium oxalate (0.75?mmol). The tube was evacuated and backfilled with argon (this procedure was repeated three times). After that, iodobenzene (0.5?mmol) and NMP (1.0?mL) were added by syringe under a counter flow of argon at room temperature. The reaction vessel was closed and then placed under stirring in a preheated oil bath. The reaction mixture was stirred for 24?h. Upon completion of the reaction, the mixture was cooled to room temperature and diluted with ethyl acetate, and analyzed by gas chromatography. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
62% | With 1,8-diazabicyclo[5.4.0]undec-7-ene; In N,N-dimethyl-formamide; at 120℃; under 7500.75 Torr; for 20h;Inert atmosphere; Autoclave; | General procedure: A 12mL vial was charged with MCM-41-2P-Pd(OAc)2 (2molpercent), 2-aminobenzamide (1mmol), aryl iodide (1mmol) (if solid) and a stirring bar. Then, DMF (2mL), aryl iodide (1mmol) (if liquid) and DBU (2mmol) were injected by syringe under an argon atmosphere. The vial was placed in an alloy plate, which was transferred into a 300mL Parr Instruments 4560 series autoclave under an argon atmosphere. After flushing the autoclave three times with CO, a pressure of 10bar CO was fixed at ambient temperature. The autoclave was heated for 20hat 120°C. After completion of the reaction, the autoclave was cooled to room temperature and the pressure was released carefully. The reaction mixture was diluted with ethyl acetate (10mL) and filtered. The palladium catalyst was washed with distilled water (2×5mL) and acetone (2×5mL), and reused in the next run. The filtrate was concentrated in vacuo and the pure product was isolated by either washed with water, ethyl acetate and finally hexane or recrystallization from MeOH. |