Radical substitution From Wikipedia, the free encyclopedia In organic chemistry, a radical-substitution reaction is a substitution reaction involving free

radicals as a reactive intermediate.[1] The reaction always involves at least two steps, and possibly a third.

In the first step called initiation (2,3) a free radical is created by homolysis. Homolysis can be brought about by heat or light but also by radical initiators such as organic peroxides or azo compounds. Light is used to create two free radicals from one diatomic species. The final step is called termination (6,7) in which the radical recombines with another radical species. If the reaction is not terminated, but instead the radical group(s) go on to react further, the steps where new radicals are formed and then react is collectively known as propagation (4,5) because a new radical is created available for secondary reactions. Radical substitution reactions[edit] In free radical halogenation reactions radical substitution takes place with halogen reagents and alkane substrates. Another important class of radical substitutions involve aryl radicals. One example is the hydroxylation of benzene by Fenton's reagent. Many oxidation and reduction reactions in organic chemistry have free radical intermediates, for example the oxidation of aldehydesto carboxylic acids with chromic acid. Coupling reactions can also be considered radical substitutions. Certain aromatic substitutions takes place by radical-

nucleophilic aromatic substitution.Auto-oxidation is a process responsible for deterioration of paints and food and lab hazards such as diethyl ether peroxide. Introduction to Free Radical Substitution Reactions in ALKANES, ALKYL HALIDES, ORGANIC CHEMISTRY 1, ORGANIC REACTIONS The four posts on acid-base, substitution, addition, and elimination covered the 4 main reactions in organic chemistry I. In this second series of posts we go beyond these to introduce a few of the less common (but still important) reactions you learn in organic chemistry 1. We talked aboutrearrangements last time: today lets talk about free-radical substitution, and leave cleavage (oxidative cleavage) for last. As Ive said with everything in this series, the point is not to understand why just yet, but to be able to see from the diagrams what bonds are broken and formed. You need to understand how to read line diagrams and also the concept of isomers. But other than that no further skills are required. The point here is to be able to follow the plot - to see what is happening. A later series of posts will go into more detail as to why things happen. Lets take two really simple examples. If you take a simple hydrocarbon like ethane (CH3CH3) and keep it in the dark with chlorine gas (Cl2), absolutely nothing happens at all.

But when you open the cover and let the light shine in, something interesting happens. As seen in the first example below, one of the hydrogens on ethane is replaced by an atom of chlorine, forming CH3CH2Cl (ethyl chloride). Along the way, we also form an equivalent of hydrochloric acid (HCl). In other words, were breaking C-H and forming C-Cl. (Why might this happen? Not going to talk about it right now. But dont forget that light (photons) carry energy, and that energy can be enough to break certain types of bonds.)

If you recall, this is very similar to the pattern we saw for substitution reactions earlier: replacement of one group at carbon for another. What makes this substitution different from the previous example is the fact that we need light or some other kind of initiator in order for the reaction to occur. Thats definitely not the case for the examples in the first substitution post. (Spoiler that name free radical substitution is going to tell us the proposed path by which this substitution occurs, but for now you can just think of it as light-dependent substitution.) The second reaction shows another example: treatment of cyclohexane with Cl2 (1 equivalent) gives cyclohexyl chloride and HCl. Same essential pattern: break C-H, form CCl. This reaction is also dependent on light being present (as will be all the reactions below). You might notice that substitution of ethane or cyclohexane with chlorine can lead to only one possible product. So what happens if you use something a little different like butane, for instance? Lets look:

See that we have two possible products 1-chlorobutane and 2-chlorobutane and theyre formed in about a 3:2 ratio. Not coincidentally, this is also the ratio of CH3 hydrogens (there are 6) to CH2 hydrogens (4). So in essence, substitution on butane is pretty much random. This also holds true if we use a more complicated alkane like 2-methylbutane. Note again that were always doing the same reaction: break a C-H bond, form a C-Cl bond. Same pattern. Different starting material, different product, but the same pattern. What happens if you use a large excess of chlorine gas? Well, it will start replacing all of the hydrogens on the hydrocarbon, like in the third example. This is the same reaction (substitution), just repeated multiple times. Nothing new here, actually! By the way: we arent using theory to predict these results, these are results that experiments tell us. Nobody predicted these results in advance. They just did the experiments, and these are the results. Thats organic chemistry. Theory comes after weve had enough experimental results to start making hypotheses. One last slide. Chlorine isnt the only halogen on the periodic table. What about fluorine (F2), bromine (Br2), and iodine (I2)?

Lets look at bromine and iodine. Fluorine well leave until the end.

Bromine is cool. When we take 2-methyl butane and treat it with bromine, we get one major product: 2-bromo-2-methyl butane. This is the major product even if we add a large excess of Br2. This is a useful property. What about iodine? Well it doesnt do much of anything, as you can see. Doesnt matter how many equivalents of iodine you add, or how much light nothing happens. Interesting! So how can we explain all of these results? How can we come up with some hypotheses to explain all of these different experimental observations? PS.OK, OK. I didnt mention fluorine. Why havent we talked about fluorine yet? Because fluorine gas is the Honey Badger Of Chemistry . It really doesnt give a shit. It will react with anything you put in front of it, and unless you are 1) extremely technically competent 2) extremely safety conscious, and 3) a little crazy, fluorine gas is something you should never, ever work with.

RADICAL CHAIN MECHANISM FOR REACTION OF METHANE WITH Br2

Step 1 (Initiation) Heat or uv light cause the weak halogen bond to undergo homolytic cleavage to generate two bromine radicals and starting the chain process. Step 2 (Propagation) (a) A bromine radical abstracts a hydrogen to form HBr and a methyl radical, then (b) The methyl radical abstracts a bromine atom from another molecule of Br2 to form the methyl bromide product and anotherbromine radical, which can then itself undergo reaction 2(a) creating a cycle that can repeat. Step 3 (Termination) Various reactions between the possible pairs of radicals allow for the formation of ethane, Br2 or the product, methyl bromide. These reactions remove radicals and do not perpetuate the cycle.

Selectivity There are two components to understanding the selectivity of radical halogenations of alkanes:

reactivity of R-H system reactivity of X.

R-H The strength of the R-H varies slightly depending on whether the H is 1o, 2o or 3o. The following table shows the bond dissociation energy, that is the energy required to break the bond in a homolytic fashion, generating

R. and H.
Type 1o 2o 3o R-H CH3-H CH3CH2-H (CH3)2CH-H (CH3)3C-H kJ/mol kcal/mol 435 104 Note how the bonds get weaker as we move down the table, so the 410 98 R. also get easier to form, with 3o 397 95 being the easiest. 380 91

Halogen radical, X.

Bromine radicals are less reactive than chlorine radicals Br. tends to be more selective in its reactions, and prefers to react with the weaker R-H bonds. The more reactive chlorine radical is less discriminating in what it reacts with.

The selectivity of the radical reactions can be predicted mathematically based on a combination of an experimentally determined reactivity factor, Ri, and a statistical factor, nHi. In order to use the equation shown below we need to look at our original alkane and look at each H in turn to see what product it would give if it were to be susbtituted. This is an exercise in recognizing different types of hydrogen, something that will be important later.

%Pi = % yield of product "i" nHi = number of H of type "i" Ri = reactivity factor for type "i" i = sum for all types

Reactivity factors, Ri Br Cl o 1 1 1 o 2 82 3.9 o 3 1640 5.2

What do the reactivity factors indicate ? Well as an example of the conclusions we could make:

Bromination is 1640 times more likely to occur at a 3o position than 1o Chlorination is 5.2 times more likely to occur at a 3o position than 1o

. Radical Halogenation of Alkanes

RADICAL CHAIN MECHANISM FOR REACTION OF METHANE WITH Br2 Step 1 (Initiation) Heat or uv light cause the weak halogen bond to undergo homolytic cleavage to generate two bromine radicals and starting the chain process. Step 2 (Propagation) (a) A bromine radical abstracts a hydrogen to form HBr and a methyl radical, then (b) The methyl radical abstracts a bromine atom from another molecule of Br2 to form the methyl bromide product and anotherbromine radical, which can then itself undergo reaction 2(a) creating a cycle that can repeat. Step 3 (Termination) Various reactions between the possible pairs of radicals allow for the formation of ethane, Br2 or the product, methyl bromide. These reactions remove radicals and do not perpetuate the cycle.

More highly brominated by-products are possible if methyl bromide reacts with a bromine radical in the same fashion as methane does. Can you draw the cycle that leads to the formation of dibromomethane ?