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11/30/2012 Preparation of an Alkyl Halide Conversion of a 3o Alcohol to 3-Chloro-3,7-dimethyloctane Nucleophilic Substitution, SN Nu: + R L SN R Nu + L: Substitution of one group for another at an sp3 hybridized carbon is a very common method of functional group interconversion. Nu: represents an atom or group of atoms that has nucleophic character. The nucleophile donates its electron pair to form a new covalent bond to carbon as the leaving group takes an electron pair with it. 1 11/30/2012 Nucleophilic Substitution All good nucleophiles in this reaction possess a non-bonding pair of electrons. Therefore, chloride ion, bromide ion, hydroxide ion, cyanide ion, water, and ammonia are typical nucleophiles. NUCLEOPHILES Cl C N Br OH HOH NH3 Nucleophilic Substitution, SN Nu: + R L SN R Nu + L: “L” represents the leaving group in this reaction. Good leaving groups are the conjugate bases of strong acids. Therefore, iodide, bromide, and chloride are good leaving groups. Hydroxide ion is a poor leaving group, but a neutral water molecule is a good leaving group. 2 11/30/2012 Alkyl Halides from Tertiary Alcohols R OH HX + R X + H2O 3o The most valuable method for synthesis of alkyl halides is synthesis from alcohols. The simplest method for converting an alcohol to an alkyl halide involves treating an alcohol with hydrogen halide. This reaction works well only with tertiary alcohols. Alkyl Halides from Tertiary Alcohols R OH HX + R X + H2O 3o Tertiary alcohols react much more rapidly in this reaction because the reaction proceeds through an SN1 reaction mechanism. Relative Reactivity in SN1 Reactions R3C 3o L > R2CH 2o L >> RCH2 L 1o 3 11/30/2012 Mechanism of SN1 Reaction of Alcohols There are three steps in the mechanism for reaction of a tertiary alcohol with HCl. The first step is protonation of the alcohol by the acid. 1) CH3 CH3 R C OH + H OH2 R Cl CH3 C CH3 OH2 + H2O Cl Mechanism – Second Step The second step of the reaction involves the slow, rate-determining loss of a neutral water molecule to form a tertiary carbocation. This is the step that accounts for the easy reaction of tertiary alcohols and very slow reaction of primary alcohols. 2) CH3 R C CH3 CH3 OH2 R slow + H2O C CH3 Cl 4 11/30/2012 Mechanism – Third Step The tertiary carbocation now undergoes a rapid reaction with the chloride ion as nucleophile to give the alkyl chloride. This reaction is essentially irreversible because the alkyl chloride forms a separate nonpolar organic layer. 3) CH3 R CH3 C CH3 fast R Cl C Cl CH3 Experimental procedure Mix 10 mL of conc. hydrochloric acid with 3.8 mL (3.17 g) of 3,7-dimethyl-3-octanol in a 50-mL Erlenmeyer flask containing a stir bar. Stir the mixture at a moderate rate for at least 20 minutes. From time to time use a plastic dropper to rinse the sides of the flask with the aqueous (upper) layer in the flask. 5 11/30/2012 Work-up and Isolation of Product Transfer the contents of the flask to a test tube and allow the layers to separate. Remove the lower, aqueous layer with a pipet. Use the Micro-extraction procedure discussed on page 70 of the lab manual to wash the organic layer, the top layer, sequentially with aqueous sodium chloride, aqueous sodium bicarbonate, and water. Work-up and Isolation of Product, Cont. Transfer the organic layer to a vial containing calcium chloride to remove water. Then filter the material through a Pasteur pipet containing a small plug of cotton into a weighed vial. Weigh the vial, cap it tightly, and label it with your name. Then store it in your section’s storage drawer until next week. 6 11/30/2012 Clean-up Aqueous phases may be disposed of in the sink. The first rinse of glassware contaminated with any organic material should be into the waste container in the hood. Safety Be careful with the concentrated hydrochloric acid. If it comes in contact with your skin, wash with large amounts of water and then sodium bicarbonate solution. Avoid contact with the silver nitrate solution. It will produce black stains on skin. Wash any affected area with soap and warm water. 7