Honors Cup Synthetic ProposalExpected yield: 78% 2.59 gExpected yield: 70% 1.76 gExpected yield: 60% 0.725 gHonors Cup Synthetic Proposal Section: 290-3 Group Members: Naomi Nemoto Stephen Chiang Kevin Brown Title: Introduction: (what makes your target interesting?) Paracetamol (Tylenol) is an analgesic drug that is used widely throughout the world. From pain relief to a simple cold, it is able to cure the human body of many ailments. Being able to synthesize Tylenol would be an exciting task as it is done regularly in the pharmaceutical field, and to create the molecule would be a step towards understanding how it aids the human body. Additionally, despite extensive studies on the crystallization of the compound, it is only very recently that the first of its solvates or adducts have been isolated and structurally characterized. These include a monohydrate and a trihydrate. Fabbiani, F.; Allan, D. R.; David, W.; Moggach, S. A.; Parsons, S.; Pulham, C. R. CrystEngComm 2004. 6, 504-511. Overall synthetic reaction scheme: (a Chemdraw or similar drawing of all three steps) HOCOCH3NOHHHOC CO OH3CCOHO CH3SOOOHH3CHONHCOCH3CH3HOCNOHCH3ONHCOCH3COH3CStep 1 Synthetic transformation 1: (Chemdraw picture of first transformation) HOCOCH3NOHHHHOCNOHCH3NaOOH2O Experimental 1 (notes if this transformation is not exactly the one reported in literature (e.g. on a different scale) and how it was modified): 4-Hydroxyacetophenone (3g, 0.022 mol) was added to a solution of hydroxylamine hydrochloride (5.13g, 0.074 mol) and sodium acetate (10.26g 0.125 mol) in water (26 ml). The solution was stirred at reflux temperature for one hour. After this time, the aqueous solution was extracted exhaustively with diethyl ether. The organic phase was dried with magnesium sulfate and the solvent (aqueous sodium acetate) evaporated under vacuum. To the resulting crude, hexane was added and the product starts to precipitate as a white solid. Baleizao, C.; Corma, A.; Garcia, H.; Leyva, A. J. Org. Chem. 2004, 69, 439-446. Corma, A.; Garcia, H.; Leyva, A. Tetrahedron 2004, 60, 8553-8560. Expected yield: 78% 2.59 g Safety, disposal and green issues 1: The green issues for this first part of synthesizing acetaminophen are compliant with the interests of the atmosphere. The solvent system used, sodium acetate along with water, are toxic to humans. This includes carcinogenicity, reproductive and developmental toxicity, neurotoxicity, and acute toxicity. Alternative solvent systems might be safer for the environment. Like sodium acetate, magnesium sulfate has similar toxicity effects on humans. The short reflux time allows for conservation of energy, in opposition to many reactions that require days and/or weeks of reflux.Step 2 Synthetic transformation 2: (Chemdraw picture of second transformation) HOCNOHCH3OC CO OH3C CH3COHO CH3ONHCOCH3COH3CAB Experimental 2 (notes if this transformation is not exactly the one reported in literature (e.g. on a different scale) and how it was modified): Compound A (2g, 0.013mol) add to acetic anhydride (1.53g 0.015mol) and then add 15ml of 80% acetic acid in a round bottom flask. Heat it under reflux for one hour. Cool to room temperature. Quench the reaction. Extract and dry with MgSO4. Recrystallize. Corma, A.; Garcia, H.; Leyva, A. Tetrahedron 2004, 60, 8553-8560. Mori, T.; Takamoto, M.; Wada, T.; Inoue, Y. Photochem. Photobiol. Sci. 2003, 2(11), 1187-1199. Expected yield: 70% 1.76 g Safety, disposal and green issues 2: For this second step, the green issues are typical of any lab substance. Both reagents are known as being irritable to eyes and skin (especially moist skin), etc.Step 3 Synthetic transformation 3: (Chemdraw picture of third transformation) ONHCOCH3COH3CSOOOHH3CHONHCOCH3BC Experimental 3 (notes if this transformation is not exactly the one reported in literature (e.g. on a different scale) and how it was modified): Compound B (1.54g, 8mmol) added to 4 ml of sulfonic acid. Heat under reflux for one hour. Cool to room temperature. Solvent evaporated and recrystallization of remaining solid. Engqvist, R.; Javaid, A.; Bergman, J. Eur. J. Org. Chem. 2004, 12, 2589-2592. Mori, T.; Takamoto, M.; Wada, T.; Inoue, Y. Photochem. Photobiol. Sci. 2003, 2(11), 1187-1199. Expected yield: 60% 0.725 g Safety, disposal and green issues 3: No major safety and green issue. Follow normal lab disposal and safety conduct.Overall budget: Chemical Supplier Cost Amt. Needed Total Ethanone MP Biomedical NV/SA $0.50 per gram 3g $1.50 NH2OH Aldrich $0.22 per mL 5.13ml $1.13 Ac2O Alfa Aesar $0.02 per gram 1.53g $0.04 AcOH Chem-Impex International Inc. $0.03 per mL 15ml $0.45 MeSO3H Acros Organics $0.03 per mL 4ml $0.12 NaOAc Chem-Implex International Inc. 0.06 per gram 7.076ml $0.43 Total costs per synthesis: ____$3.67_________ References (include at least two different sources for your
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