Honors Cup Synthetic ProposalExpected yield: 54% 1.8gExpected yield: 73% 1.3gExpected yield: 97% 1.26gHONORS CUP SYNTHETIC PROPOSAL Adrenaline From mild to wild Angelique Sao‐Mai Do Brittany Mitchell Jonathan Browalski Honors Cup Synthetic Proposal Section: 231 – Group I Group Members: Angelique Do, Jonathan Browalski, Brittany Mitchell Title: Synthesizing Epinephrine Introduction: Epinephrine, or adrenaline, is an important chemical that has a huge impact as a hormone in the human body. It is a neurotransmitter and is secreted in the adrenal gland. It is responsible in large part for the “flight or fight” evolutionary reaction. In an emergency situation, it boosts the supply of oxygen and glucose to the brain and muscles and suppresses non‐emergency bodily processes such as digestion. It also suppresses the immune system, and causes the breakdown of lipids in fat cells to provide additional energy. Additionally, it causes an increased heart rate and stroke volume. Being able to synthesize epinephrine is important because it is used as a drug to treat cardiac arrest and other cardiac dysrhythmias. Due to its effect on the immune system, epinephrine is also used to treat anaphylaxis and sepsis. Because of its use in treating health disorders and as an interesting hormone naturally produced by the central nervous system, synthesizing epinephrine is a worthwhile goal. Overall synthetic reaction scheme: OHOHOHHOOClCl CO2HCOHHOONHCHOHHOOHNH Section 231 – Group I 1Step 1 Synthetic transformation 1: OOHOHOHHOClClCH2CO2H+R: POCl3,R:SO2 Experimental 1: “Fifty grams each of monochloroacetic acid, catechol, and freshly distilled phosphorus oxychloride were mixed together in a one‐liter short‐necked flash fitted with reflux condenser and a tube through which sulfur dioxide was passed. A tube was attached to the end of the reflux condenser to lead away hydrogen chloride gas evolved in the reaction, and the sulfur dioxide. After the flask was filled with the sulfur dioxide from a tank, heating was started, a steady stream of gas always flowing. At the end of an hour heating was stopped, the purple crystals of crude chloroaceto‐catechol crystallized from hot water, decolorized with acid, Norite and sodium sulfite, and again crystallized. The light violent tinged crystals were washed with absolute alcohol, and finally ether.” Modifications: • Rather than using sulfur dioxide, we could use nitrogen gas to prevent oxidation of catechol and undesirable side products. Sulfur dioxide also happens to be a very environmental unfriendly molecule. • We won’t be using fifty grams of each, but 2 grams of each. • Replace norite, a drying agent, and sodium sulfite with magnesium sulfate. • Possible: Should the use of phosphorus oxycholoride be unpractical due to toxicity levels, we could use aluminum trichloride. Expected yield: 54% 1.8g Safety, disposal and green issues 1: Safety Issues: 1. Catechol • Is a carcinogen, corrosive, and combustile • Suspected to be cardiovascular, gastrointestinal, liver, immuno, and neurotoxicant • Skin toxicant; readily absorbed through skin Section 231 – Group I 2• Harmful if inhaled, but relatively negligible evaporation at 20 degrees; for personal safety, the use of a respirator is advised • Reactive with oxidants • For cleaning up any spills, first moisten to prevent dusting. 2. Monochloroacetic Acid • Deliquescent (absorbs water from the air) • Corrosive – can cause severe burns • Harmful if swallowed or inhaled • Severe respiratory irritant • Chronic exposure may lead to CNS damage 3. Phosphorus Oxychloride • Reacts violently with water; hydrolyzes in moist air to phosphoric acid to release choking fumes of hydrogen chloride; can cause delayed pulmonary edema • May be fatal if inhaled, swallowed, or absorbed through skin • Can cause serious eye damage • Corrosive; can cause serious, possibly fatal burns • Use only under chemical fume hood 4. Aluminum Trichloride (possible replacement for phosphorus oxychloride) • Eye, skin, and respiratory irritant • Not considered to be a fire hazard Green Issues: 1. Catechol: Toxic to aquatic organisms; must be kept out of the environment 2. Monochloroacetic Acid • Does not bioaccumulate • Low vapor pressure indicates that a significant amount is not present in the atmosphere • Readily biodegrades • Not an ecotoxin 3. Phosphorus Oxychloride: May have long term adverse effects in aquatic environments 4. Aluminum Trichloride (possible replacement for phosphorus oxychloride): Hydrolyzes in water to aluminum hydroxide and hydrochloric acid Disposal: Whatever can not be saved for recovery or recycling, should be handled as hazardous waste and sent to a RCRA approved incinerator or disposed in a RCRA approved waste facility. If there is any spillage, soak it up with a non‐reactive substance, such as sand. Dispose in a solid waste container. Section 231 – Group I 3Step 2 Synthetic transformation 2: Experimental 2: “Monochloroacetocatechol is mixed with a solvent and reactant system of 40% MeNH2 in H2O. Cool for 30 min ice bath. Purify as HCl salt.” Modifications: • Do not purify as a HCl salt. • We are using 2 g of methyl amine. Expected yield: 73% 1.3g Safety, disposal and green issues 2: Safety Issues for Methyl Amine: • Flammable • Incompatible with oxidizing agents, acids, alkalis, alkaline earth metals, copper, and zinc • Harmful if inhaled • Destructive to mucous membranes • Corrosive Green Issues for Methyl Amine: • Not a serious environmental hazard Disposal: Whatever can not be saved for recovery or recycling, should be handled as hazardous waste and sent to a RCRA approved incinerator or disposed in a RCRA approved waste facility. If there is any spillage, soak it up with a non‐reactive substance, such as sand. Dispose in a solid waste container. Section 231 – Group I 4Step 3 Synthetic transformation 3: Experimental 3: Add the triethylamine and solvent (benzene) to the previous product. Stir briefly. Add the catalyst (Rh CCD Cl dimer) and diphenylsilane. Allow reaction to sit for several hours at room temperature. Add hydrochloric acid and water to the mixture. Dry and recrystallize for purification. Test for presence of product via
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