Honors Cup Group IV Section 231 Lauren Leader, Nikola Collins, Anuj Shah 1/25/08 Proposal Honors Cup Proposal Title: Synthesis of Relief Introduction: Ibuprofen is an over the counter pain reliever and is used as an alternative to Tylenol. It is an anti-inflammatory. It is used for relief of symptoms of arthritis, fever, and as a blood thinner. History: Ibuprofen was discovered by the Boots Group, the dominant pharmacy chain in the UK, in the ‘60’s. It was initially launched to heal rheumatoid arthritis. Racemic mixtures do not affect the human body, in fact, most of ibuprofen is manufactured in racemic mixtures. However, the S-conformation in the one chiral carbon ibuprofen has is the active ingredient. Since that one conformation is very hard to produce, and its enantiomer has no negative effect on the body, it is acceptable to have a mixture. Reaction Scheme: OClOAlClClClIIHCOOOONaOHHOO Journal of Organic Chemistry, 53(20), 4858-9; 1988 Chemical & Pharmaceutical Bulletin, 31(9), 3139-48; 1983 Synthesis, (12), 1044-5; 1986Honors Cup Group IV Section 231 Lauren Leader, Nikola Collins, Anuj Shah 1/25/08 Proposal STEP 1 OClAlOAlClClClClOHHO In step one, Electrophilic Aromatic Substitution occurs in which pi electrons from the double bonds of the benzene react with a good electrophile (EtC(=O)Cl). This reaction is very similar to the one done in experiment one (Friedel-Crafts Acylation reaction). First, Anhydrous aluminum chloride and propanoyl chloride should be mixed and flushed with nitrogen in a flask. Then cool temperature to zero degrees Celsius. Then the aromatic compound is added in the same manner. After stirring for an additional 15 minutes at room temperature, the reaction mixture was poured carefully and slowly, with stirring, into ice and HCl in a beaker. Separatory funnel was used to separate the organic layer from the aqueous. Separation through differing boiling points and additional seperatory methods were used to separate the reactants and solution from the products. Expected Yield: 0.52744 grams Safety, disposal and green issues 1: Acetyl Chloride: Safety: Flammable liquid and vapor. Corrosive. May cause central nervous system depression. Causes eye and skin burns. May cause severe respiratory tract irritation with possible burns. May cause severe digestive tract irritation with possible burns. Water-reactive. Disposal: RCRA P-Series: None listed. RCRA U-Series: CAS# 75-36-5: waste number U006 (Corrosive waste, Reactive waste, Toxic waste). Green Issues: NoneHonors Cup Group IV Section 231 Lauren Leader, Nikola Collins, Anuj Shah 1/25/08 Proposal Isobutylbenzene: Safety: Flammable liquid and vapor. Causes eye, skin, and respiratory tract irritation. Aspiration hazard if swallowed. Can enter lungs and cause damage. May cause central nervous system depression. Marine pollutant. Target Organs: Central nervous system, lungs. Disposal: Chemical waste generators must determine whether a discarded chemical is classified as a hazardous waste. US EPA guidelines for the classification determination are listed in 40 CFR Parts 261.3. Additionally, waste generators must consult state and local hazardous waste regulations to ensure complete and accurate classification. Green issues: Ecotoxicity: Algae: 35 mg/l; 96 hr; LC50 Sheepshead minnow: > 200 mg/l; 96 hr; LC50 Propanoyl Chloride: Safety: Corrosive. Causes eye and skin burns. Water-reactive. Reacts violently and/or explosively with water, steam or moisture. Flammable liquid and vapor. May ignite or explode on contact with moist air. Lachrymator (substance which increases the flow of tears). May cause severe respiratory tract irritation with possible burns. May cause severe digestive tract irritation with possible burns. Disposal: Chemical waste generators must determine whether a discarded chemical is classified as a hazardous waste. US EPA guidelines for the classification determination are listed in 40 CFR Parts 261.3. Additionally, waste generators must consult state and local hazardous waste regulations to ensure complete and accurate classification. Green Issues: No information is availableHonors Cup Group IV Section 231 Lauren Leader, Nikola Collins, Anuj Shah 1/25/08 Proposal STEP 2 Step two involves the synthesis of methyl 2- arylpropanoates by treatment of the product of reaction one with Iodine. The chemistry of the reaction is similar to the example that follows. OI IO OTMOFIII-CH3IOO 1= Benzene product from step one. Yield for this product is expected to be 93% of methyl ibuprofen (starting material of Step 3). This step is quite easy to carry out. First carry out a mixture of the products from step one with TMOF (trimethyl orthoformate) in a round bottom flask. Then stir this mixture until it looks homogenous. After this is accomplished, add the I2 at a temperature of 27° C and stir for twenty four hours. Expected Yield: 0.592837 grams A facile and efficient preparative method of methyl 2-arylpropanoates by treatment of propiophenones and their derivatives with iodine or iodine chlorides Yamauchi, Takayoshi, Hattori, Kaneaki, Nakao, Kenji, and Tamaki, Kentaro J. Org. Chem., 53, 20, 4858 - 4859, 1988, 10.1021/jo00255a037 Safety, disposal and green issues 2: Trimethoxymethane: Safety: Hazardous in case of eye contact (irritant), of inhalation (lung irritant). Slightly hazardous in case of skin contact (irritant), of ingestion, CARCINOGENIC EFFECTS: Not available. MUTAGENIC EFFECTS: Not available. TERATOGENIC EFFECTS: Not available. DEVELOPMENTAL TOXICITY: Not available. TheHonors Cup Group IV Section 231 Lauren Leader, Nikola Collins, Anuj Shah 1/25/08 Proposal substance may be toxic to upper respiratory tract, skin, eyes. Repeated or prolonged exposure to the substance can produce target organs damage. Disposal: Waste must be disposed of in accordance with federal, state and local environmental control regulations. Green Issues: Ecotoxicity: Not available. BOD5 and COD: Not available. Products of Biodegradation: Possibly hazardous short term degradation products are not likely. However, long term degradation products may arise. Toxicity of the Products of Biodegradation: The product itself and its products of degradation are not toxic. Special Remarks on the Products of Biodegradation: Not available. Iodine: Safety: Safety glasses, nitrile gloves. Effective ventilation. Disposal: RCRA P-Series: None listed. RCRA U-Series:
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