Classification of Alkyl Halides ⚫ Alkyl halides are organic molecules containing a halogen atom bonded to an sp³ hybridized carbon atom. • Alkyl halides are classified as primary (1°), secondary (2°), or tertiary (3°), depending on the number of carbons bonded to the carbon with the halogen atom (denoted by the symbol "X"). Copyright the McGraw-Hill Companies Inc. Permission required for reproduction or display Lab 9-S1 Experiment Overview In this experiment, you will form an alkyl halide from a tertiary alcohol. Specifically, you will convert 2-methyl- 2-butanol (t-amyl alcohol or t-pentyl alcohol) to 2-chloro-2-methyl butane (t-amyl chloride or t-pentyl chloride) as shown as Figure SN.7 Alkyl halide Classification of alkyl halides H H-C-X H H R R R-C-X R-C-X R-C-X H H sp hybridized C methyl halide R-X X-F, Cl, Br, I 1 (one R group) 25 (two R groups) R 3 (three R groups) Figure SN.1. Classifications of alkyl halides Reactions of Alkyl Halides: Alkyl Halides undergo two types of Reactions, these are Substitution Reactions and Elimination Reactions see Figure SN.2 + HCI Figure SN.7 + H₂O The starting alcohol, 2-methyl-2-butanol, is soluble in water while the product, 2-chloro-2-methylbutane, is insoluble in water. When 2-chloro-2-methylbutane formed, it immediately separates from the aqueous layer and creates a new organic layer. If two or more layers exist in a centrifuge tube, you can determine the identity of the aqueous layer by adding drops of water to the tube and observing the layer into which the droplets merge. NOTE: . a substitution reaction RCH-CHY + X RCH CHX + Y RCH=CH2 +HY + X an elimination reaction the leaving group Figure SN.2. 4/1/2025 . Your starting material is a tertiary alcohol Carbocation intermediate (3°, most stable) forms quickly. Nucleophile is a weak base and strong nucleophile (CH), S1 Reaction Product is a substitution product Leaving group is water molecule Reactions of Alkyl Halides: Substitution and Elimination Alkyl Halides undergo two types of Reactions, these are Elimination reaction . the halide ion is eliminated along with another atom (often H") to form an Alkene. eliminations of alkyl halides are called dehydrohalogenations because a hydrogen halide has been removed from the alkyl halide. Substitution reaction • . the halogen atom (leaving group) is replaced (substituted) by another group (nucleophile), halogen atom leaves with its bonding electron pair form a stable halide ion. Substitution reactions involves sigma(o) bonds only, one σ bond breaks and a new σ bond forms at the same carbon atom. In any substitution reaction three components are necessary. 1. sp³ hybridized carbon 2. Nucleophile 3. Leaving group Conversion of Alcohols to Alkyl Halides by Substitution Reactions ⚫ Alkyl halides can be formed by reaction of alcohols with H-X acids, see Figure SN.3 In acidic media, the alcohol is in equilibrium with its protonated form. The -OH is a poor leaving group, but -OH is an excellent leaving group because upon cleavage it forms a neutral molecule, once the -OH is protonated, it becomes a good leaving group, the molecule may take part in a variety of substitution and/or elimination reactions. ANALYSIS: The presence of primary and secondary chlorides or bromides can be confirmed by reacting the product with sodium iodide in acetone. The byproduct, sodium halide, is insoluble acetone and crashes out. The precipitate is indicative of a positive test (Figure SN.8). Nal Acetone H NaBri Figure SN.8: Substitution reaction in the sodium iodide test Silver Nitrate Analysis Silver nitrate is one of the very few water-soluble silver salts. Silver nitrate reacts with an alkyl halide to form silver halide, this is insoluble and will appear as a white cloud or a white precipitate. The presence of a tertiary alkyl halide can be determined by reacting a small amount of your product with a solution of silver nitrate in ethanol. Tertiary alkyl halides react rapidly by an SN1 mechanism with the AgNO3 to form a precipitate of AgCl(s) (Figure SN.9). Ag NO AgCl(s) + NO Figure SN.9. R-O-H + H 2 R-X R-O-H Sylor S2 R-X Figure SN.3. Ag +H₂O Alkyl halide silver ion water R-OH + AgX (ppt) +H* alcohol silver halide poor leaving group good leaving group 9 Conversion of Alcohols to Alkyl Halides by Substitution Reactions The nature of R determines whether the reactions proceed via SN1 or SN2 mechanisms. If the substrate is a primary alkyl, then an SN2 reaction will occur. If the substrate is a bulky, tertiary alkyl, then an SN1 reaction will occur. The general pattern is shown in Figure SN.3. Reactions of alcohols with non nucleophilic acids (Sulfuric acid, Phosphoric acid) produce elimination products. The conjugate base (SO4) of these acids are not nucleophilic Reactions of alcohols with acids like Hydrogen halides (HCI, HBr), produce substitution product predominantly. The reasons for this behaviour is that the conjugate base of these acids are very nucleophilic (Cl-, Br-or I-). This nucleophilic weak conjugate base then adds to the carbocation and substitution occurs. Low temperature (room temperature and below) favors SN1. SN1 Mechanism In an S, 1 reaction between an alcohol and a hydrogen halide (Figure SN.4), the alcohol is first protonated by the hydrogen halide. . The protonated alcohol (an oxonium ion) then loses a molecule of water to form a carbocation intermediate in the rate-determining step. The carbocation is then rapidly attacked by the halide ion (X), producing the alkyl halide. Substrates that can form relatively stable carbocations react fastest in an S,, 1 pathway. . Since tertiary alcohols form more stable carbocation intermediates than primary and secondary alcohols, tertiary alcohols are the most likely to react with hydrogen halides through the S, 1 pathway. ⚫ Because S, 1 reactions go through carbocation intermediates, both rearrangements and competing elimination reactions may occur. Purpose of Hydrogen Chloride? In this Experiment Convert alcohol into a good leaving group. Provide a strong nucleophile, Ct. What is the limiting reactant? 2-methyl-2-butanol Solvent in this Experiment? HCI (Hydrochloric acid) Purpose of Sodium bicarbonate? Neutralized excess acid HCI; Products are CO, and H₂O Purpose of Sodium sulfate? Anhydrous Sodium sulfate is a dehydrating (drying) agent. It absorbs water from materials with which it comes in contact. S1 Reaction Mechanism of 2-methyl-2-butanol with HCI Substrates that form stable carbocation reacts via an S,1 pathway Weak base, strong Nucleophile H₂O leaving group - CH H HC-C-- CH 4/1/2025 CH CH HC-C H Figure SN.4. CH CH S2 Mechanism In an S, 2 reaction between an alcohol and a hydrogen halide (Figure SN.5), the alcohol is also protonated. The nucleophile displaces water from the oxonium ion through a bimolecular transition state. Alcohols with little steric hindrance, such as primary alcohols, react with hydrogen halides most rapidly through this mechanism. CH-CH-CH --H H CHCH CH H butun-1-ol CH-CH-CH + HO Figure SN.5. 1-bromabuland The S,2 process is not observed for tertiary alcohols since the transition state is too crowded, the rate of S1 reaction increases. Secondary Alcohols Secondary alcohols can react via either mechanism depending on reaction conditions (see Table SN.1), the-OH group is a poor leaving group so direct halide displacement is not a good synthetic option - however the hydroxyl group can be easily converted into other groups (e.g. tosylates) that are superior leaving groups, substitution of the tosylate with a halide can then proceed (Figure SN.6). OH TvC1 Pyridine {༣ / OTS Nuc (substitution) + OTS Nue Figure SN.6: SN2 reaction of a tosylate 2-methyl-2-butanol Oxonium lon к 2-chloro-2-methylbutane tertiary carbocation, very stable 2) Using chemical structures draw the complete chemical reaction mechanism of the reaction of 2 methyl 2 butanol with HCI, provide all the products and any intermediates involved (1.0 point) 3) For reaction drawn above, what is the theoretical yield if you started with 1.5 mL of 2 methyl 2 butanol (MW = 88.15 g/mol; density = 0.805 g/mL) and excess HCI to produce the product (MW= 106.59.15 g/mol)? .1 point