Download Preparation of alkyl halides There are lots of ways to make alkyl

Preparation of alkyl halides There are lots of ways to make alkyl halides. Key benefit to alkyl halides is that the C‐X bond is particularly useful for other functional group transformations, which we will talk about in the “reactivity of alkyl halides” section. 1. Preparation of alkyl halides from alcohols: The overall reaction is shown below: This works best with tertiary alcohols (things with 3 carbon atoms attached to the OH containing carbon), and is slower for reactions of primary and secondary alcohols. We will discuss the mechanism of this reaction in detail (which explains why tertiary alcohols are the fastest) during the next class, although a key feature is that the strong acid protonates the OH group, so that the ‘leaving group’ becomes a neutral water molecule. If you want to react primary or secondary alcohols to form the corresponding halides, you usually have to use one of the special halogenating agents shown below: You use some kind of base in each of these cases (either triethylamine or pyridine) so that you can neutralize the acid that is formed during the reaction. The key feature of these reactions is that you are converting OH into a much better leaving group as well. 2. Preparation of alkyl halides from alkenes: Here you have several options, many of which you should have seen at some point last semester 2a. Addition of HX across an alkene double bound: The halide always ends up on the more substituted carbon, which is predicted by Markovnikov’s rule, which states, “when an unsymmetrical alkene reacts with a hydrogen halide to give an alkyl halide, the hydrogen adds to the carbon that has the greater number of hydrogen substituents, and the halogen to the carbon having the fewer number of hydrogen substituents.” The reason for this observed rule can be explained by the mechanism: The first step is protonation which will occur to give the more stable (i.e. more substituted) carbocation: The more stable carbocation then reactions with the bromide nucleophile to generate the final product: 2b. Addition of X2 across a double bond The overall reaction is shown below: The stereochemistry observed for this case is always anti, which can be explained by a mechanism that involves a 3‐membered bromonium ion: First step is nucleophilic attack of the double bond on the bromine, to form a positively charged bromonium ion and a negatively charged bromine anion. Then the anion acts as a nucleophile to attack the three membered ring, and form the dihalogenated final product. 2c. Alkenes can also form alkyl halides using radical chemistry. There are a number of ways in which this can occur, but we will focus only o the one that your book discusses, which is addition of a bromine to an alylic position of a starting material using NBS (N‐
bromosuccinimide). The structure of NBS is shown below: And the overall allylic bromination reaction is shown below: This reaction is pretty selective to add the bromine radical only to the allylic position. The reason for this selectivity is that the allylic radicals that form are the most stable radicals, because they can be resonance stabilized due to their proximity to the double bond: So once we have made the alkyl halides, what do we do with them? Lots and lots of reactions! One key reaction is a ‘substitution reaction’ – where the alkyl halide is substituted by another functional group. There are two main types of substitution reactions, called SN1 and SN2 reactions. We will discuss the mechanisms of those reactions in detail next class. The overall substitution reaction is shown below: R‐X + Nucleophile ‐ R‐Nucleophile + X‐ where the X (representing a halogen) gets displaced by a nucleophile to form a new bond between the carbon and the incoming nucleophile. This substitution reaction is exceptionally useful because we can generate lots of different compounds very easily this way: