Chapter 10: Organohalides
A polar C-X bond, and three ways to classify the carbon that carries it
An organohalide is any compound with a carbon-halogen bond, and the alkyl halides of this chapter place that halogen on an sp3 carbon. The defining structural feature is the polarity of the bond. Fluorine, chlorine, bromine, and iodine are all more electronegative than carbon, so bonding electrons are pulled toward the halogen, leaving carbon with a partial positive charge. That is the electrophilic carbon a nucleophile will later attack. Two separate trends run down the halogen column and it is worth keeping them apart. First, electronegativity decreases from fluorine to iodine, so the…
A radical chain: initiation, propagation, termination, and the reactivity-selectivity trade
Radical halogenation is the classic way to put a halogen on an unfunctionalized alkane, and its mechanism is a chain reaction built from three kinds of steps. Initiation creates the first radicals: heat or ultraviolet light homolyzes the weak X-X bond of Cl2 or Br2 so that each atom leaves with one of the two bonding electrons, giving two neutral halogen atoms. These steps move single electrons, so they are drawn with fishhook (single-barbed) arrows, not the two-electron arrows of ionic mechanisms. Propagation is the cycle that actually turns starting material into product, and it consumes no…
NBS brominates the allylic position instead of adding across the double bond
Alkenes present a choice. Molecular bromine will add across the double bond by an ionic mechanism to give a vicinal dibromide, but the carbons next to the double bond, the allylic carbons, carry C-H bonds that a radical will attack. Which pathway dominates depends almost entirely on the concentration of Br2. Ionic addition needs an appreciable concentration of bromine, while the radical allylic substitution proceeds happily at a very low one, so the trick is simply to keep the bromine concentration low. That is exactly what N-bromosuccinimide accomplishes. NBS is a stable, easily handled…
The allylic radical is delocalized over two carbons, and that can give two products
The reason allylic bromination targets the allylic position is the stability of the radical produced there, and that stability comes from resonance. When the allylic C-H breaks, the carbon left with the unpaired electron has a singly occupied p orbital positioned right next to the p orbitals of the double bond. These overlap, so the unpaired electron is not stuck on one atom: it is spread across the first and third carbons of an allylic three-carbon unit, and the double bond is correspondingly spread over the same span. We represent this with two resonance structures, one showing the radical…
Turning an alcohol into an alkyl halide: HX for tertiary, PBr3 or SOCl2 for the rest
Because alcohols are among the most available organic compounds, converting them to alkyl halides is the workhorse preparation of this functional group. The choice of reagent tracks the class of the alcohol, and understanding why avoids a lot of memorization. A tertiary alcohol needs nothing more than concentrated aqueous HCl or HBr. The acid protonates the hydroxyl oxygen, converting the terrible leaving group hydroxide into water, and because a tertiary center forms a carbocation readily, loss of water gives a stable tertiary cation that the halide ion then captures. The reaction is fast at…
R-MgX inverts the polarity of carbon and is quenched by any acidic hydrogen
Organometallic reagents are the payoff of the chapter, because they take a carbon that was electrophilic and make it nucleophilic. To make a Grignard reagent, an alkyl, vinyl, or aryl halide is stirred with magnesium metal in an anhydrous ether solvent such as diethyl ether or tetrahydrofuran. The magnesium inserts into the carbon-halogen bond to give R-MgX, a species in which carbon is now bonded to an electropositive metal. Treating the same halide with lithium metal instead gives an organolithium reagent, R-Li, which is similar but even more reactive. The conceptual heart of this is a…
Diorganocopper coupling builds C-C bonds; oxidation-state bookkeeping tracks H and heteroatoms
Two threads close the chapter: one new reaction that forms carbon-carbon bonds, and a bookkeeping skill that runs through all of organic chemistry. The reaction is organometallic coupling. Start by making an organolithium reagent from an organohalide and lithium, then treat two equivalents of it with copper(I) iodide. The product is a lithium diorganocopper reagent, R2CuLi, traditionally called a Gilman reagent. Its value is that it couples: when it encounters a separate organohalide R'-X, one of the organic groups on copper is transferred and bonds to R', producing R-R' and thereby stitching…
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