Organic Chemistry Second Edition Chapter 11 David Klein

Organic Chemistry Second Edition Chapter 11 David Klein
Radical Reactions Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

11.1 Free Radicals Free radicals form when bonds break homolytically
Note the single-barbed or fishhook arrow used to show the electron movement Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

11.1 Free Radicals Free radicals can be thought of as sp2 hybridized or quickly interconverting sp3 hybridized sp2 hybridized Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

11.1 Free Radical Stability
Free radicals do not have a formal charge but are unstable because of an incomplete octet Groups that can push (donate) electrons toward the free radical will help to stabilize it. WHY? HOW? Consider hyperconjugation Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

11.1 Free Radical Stability
Use arguments that involve hyperconjugation and an energy diagram to explain the differences in bond dissociation energy below Practice with conceptual checkpoint 11.1 Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

11.1 Free Radical Resonance
Drawing resonance for free radicals using fishhook arrows to show electron movement Remember, for resonance, the arrows don’t ACTUALLY show electron movement. WHY? Draw the resonance hybrid for an allyl radical HOW and WHY does resonance affect the stability of the free radical? Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

11.1 Free Radical Resonance
The benzylic radical is a hybrid that consists of 4 contributors Draw the remaining contributors Draw the hybrid Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

11.1 Resonance Stabilization
How does resonance affect the stability of a radical? WHY? What is a bigger factor, hyperconjugation or resonance? Practice with SkillBuilder 11.1 Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

11.1 Resonance Stabilization
Vinylic free radicals are especially unstable What type of orbital is the vinylic free radical located in, and how does that affect stability? Practice with SkillBuilder 11.2 No resonance stabilization Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

11.2 Radical Electron Movement
Free radical electron movement is quite different from electron movement in ionic reactions For example, free radicals don’t undergo rearrangement There are SIX key arrow-pushing patterns that we will discuss Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

Homolytic Cleavage: initiated by light or heat Addition to a pi bond Hydrogen abstraction: NOT the same as proton transfer Halogen abstraction Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

Elimination: the radical from the α carbon is pushed toward the β carbon to eliminate a group on the β carbon (reverse of addition to a pi bond) The –X group is NOT a leaving group. WHY? Coupling: the reverse of homolytic cleavage Note that radical electron movement generally involves 2 or 3 fishhook arrows Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

Radical electron movement is generally classified as either initiation, termination, or propagation Initiation Termination Initiation occurs when radicals are created Termination occurs when radicals are destroyed Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

11.3 Chlorination of Methane
Let’s apply our electron-pushing skills to a reaction We must consider each pattern for any free radical that forms during the reaction Is homolytic cleavage also likely for CH4? Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

The propagation steps give the net reaction Initiation produces a small amount Cl• radical H abstraction consumes the Cl• radical Cl abstraction generates a Cl• radical, which can go on to start another H abstraction Propagation steps are self-sustaining Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

Reactions that have self-sustaining propagation steps are called chain reactions Chain reaction: the products from one step are reactants for a different step in the mechanism Polychlorination is difficult to prevent, especially when an excess of Cl2 is present. WHY? Practice with SkillBuilder 11.4 Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

Draw a reasonable mechanism that shows how each of the products might form in the following reaction Which of the products above are major and which are minor? Are other products also possible? Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

11.3 Radical Initiators An initiator starts a free radical chain reaction Which initiator above initiates reactions most readily? WHY? The acyl peroxide will be effective at 80 °C Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

11.3 Radical Inhibitors Inhibitors act in a reaction to scavenge free radicals to stop chain reaction processes Oxygen molecules can exist in the form of a diradical, which reacts readily with other radicals. Use arrows to show the process How can reaction conditions be modified to stop oxygen from inhibiting a desired chain reaction? Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

11.3 Radical Inhibitors Hydroquinone is also often used as a radical inhibitor Draw in necessary arrows in the reactions above Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

11.4 Halogenation Thermodynamics
If we want to determine whether a process is product favored, we must determine the sign (+/-) for ΔG In a halogenation reaction, will ΔH or -TΔS have a bigger effect on the sign of ΔG? WHY? Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

Because the -TΔS term should be close to zero, we can simplify the free energy equation Considering the bonds that break and form in the reaction, estimate ΔHhalogenation for each of the halogens in the table below Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

Fluorination is so exothermic that it is impractical. WHY does that make it impractical? Iodination is nonspontaneous, so it is not product favored Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

Which step in the mechanism is the slow step? Which reaction has a faster rate? Which is more product favored? First step is endothermic Both steps are exothermic Second step is exothermic Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

11.5 Halogenation Regioselectivity
With substrates more complex than ethane, multiple monohalogenation products are possible If the halogen were indiscriminant, predict the product ratio? Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

For the CHLORINATION process, the actual product distribution favors 2-chloropropane over 1-chloropropane Which step in the mechanism determines the regioselectivity? Show the arrow pushing for that key mechanistic step Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

In one reaction, a 1° free radical forms, and in the other a 2° radical forms Is the chlorination process thermodynamically or kinetically controlled? WHY? Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

For the BROMINATION process, the product distribution vastly favors 2-bromopropane over 1-bromopropane Which step in the mechanism determines regioselectivity? Show the arrow pushing for that key mechanistic step Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

Is the key step in the bromination mechanism kinetically or thermodynamically controlled? WHY? First step is endothermic Both steps are exothermic Second step is exothermic Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

Focus on the H abstraction step, and consider the Hammond postulate: species on the energy diagram that are similar in energy are similar in structure Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

When the bromine radical abstracts the hydrogen, the carbon must be able to stabilize a large partial radical When the chlorine radical abstracts the hydrogen, the carbon does not carry as much of a partial radical Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

Which process is least regioselective? WHY? What is the general relationship between reactivity and selectivity? WHY? Practice with SkillBuilder 11.5 Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

Ignoring possible addition products for now, draw the structure for EVERY possible monobromination product for the reaction below Rank the products in order from most major to most minor Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

11.6 Halogenation Stereochemistry
The halogenation of butane or more complex alkanes forms a new chirality center 2-chlorobutane will form as a racemic mixture Which step in the mechanism is responsible for the stereochemical outcome? Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

Whether the free radical carbon is sp2 or a rapidly interconverting sp3, the halogen abstraction will occur on either side of the plane with equal probability sp2 hybridized Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

Three monosubstituted products form in the halogenation of butane Draw all of the monosubstituted products that would form in the halogenation of 2-methylbutane including all stereoisomers Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

In the halogenation of (S)-3-methylhexane, the chirality center is the most reactive carbon in the molecule. WHY? Name the product and predict the stereochemical outcome Practice with SkillBuilder 11.6 Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

Draw all of the monosubstituted products that would form in the halogenation below including all stereoisomers Classify any stereoisomer pairs as either enantiomers or diasteriomers Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

11.7 Allylic Halogenation When an C=C double bond is present it affects the regioselectivity of the halogenation reaction Given the bond dissociation energies below, which position of cyclohexene will be most reactive toward halogenation? Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

11.7 Allylic Halogenation When an allylic hydrogen is abstracted, it leaves behind an allylic free radical that is stabilized by resonance Based on the high selectivity of bromination that we discussed, you might expect bromination to occur as shown below What other set of side-products is likely to form in this reaction? Hint: addition reaction Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

11.7 Allylic Halogenation with NBS
To avoid the competing halogenation addition reaction, NBS can be used to supply Br• radicals Show how resonance stabilizes the succinimide radical Heat or light initiates the process Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

Propagation produces new Br• radicals to continue the chain reaction Where does the Br-Br above come from? The amount of Br-Br in solution is minimal, so the competing addition reaction is minimized Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

The succinimide radical that is produced in the initiation step can also undergo propagation when it collides with an H-Br molecule. Show a mechanism + H-Br Give some examples of some termination steps that might occur Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

Give a mechanism that explains the following product distribution. Hint: resonance Practice with SkillBuilder 11.7 Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

11.8 Atmospheric Chemistry and O3
Ozone is both created and destroyed in the upper atmosphere O3 molecules absorb harmful UV radiation O3 molecules are recycled as heat energy is released Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

For this process to be spontaneous, the entropy of the universe must increase Heat is a more disordered form of energy than light. WHY? Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

O3 depletion (about 6% each year) remains a serious health and environmental issue Compounds that are most destructive to the ozone layer Are stable enough to reach the upper atmosphere Form free radicals that interfere with the O3 recycling process Chlorofluorocarbons (CFCs) fit both criteria Atmosphere O3 is vital for protection, but what effect does O3 have at the earth’s surface? Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

CFC substitutes that generally decompose before reaching the O3 layer include hydrochlorofluorocarbons Hydrofluorocarbons don’t even form the chlorine radicals that interfere with the O3 cycle Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

11.8 Combustion and Firefighting
Like most reactions, combustion involves breaking bonds and forming new bonds A fuel is heated with the necessary Eact to break bonds (C-C, C-H, and O=O) homolytically The resulting free radicals join together to form new O-H and C=O bonds Why does the process release energy overall? What types of chemicals might be used in fire extinguishers to inhibit the process? Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

Water deprives the fire of the Eact needed by absorbing the energy CO2 and Argon gas deprive the fire of needed oxygen Halons are very effective fire-suppression agents Halons suppress combustion in three main ways Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

Halons suppress combustion in three main ways As a gas, they can smother the fire and deprive it of O2 They absorb some of the Eact for the fire by undergoing homolytic cleavage The free radicals produced can combine with C• and H• free radicals to terminate the combustion chain reaction Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

How do you think the use of halons to fight fires affects the ozone layer? FM-200 is an alternative firefighting agent Practice with conceptual checkpoint 11.18 Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

11.9 Autooxidation Autooxidation is the process by which compounds react with molecular oxygen The process is generally very slow Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

11.9 Autooxidation Mechanism
The mechanism illustrates the need for a more refined definition of initiation and propagation. HOW? Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

11.9 Autooxidation Mechanism
Propagation can be more precisely defined as the steps that add together to give the net chemical equation Steps in the mechanism that are not part of the net equation must be either initiation or termination Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

11.9 Autooxidation Some compounds such as ethers are particularly susceptible to autooxidation Because hydroperoxides can be explosive, ethers like diethyl ether must not be stored for long periods of time They should be dated and used in a timely fashion Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

11.9 Autooxidation Light accelerates the autooxidation process
Dark containers are often used to store many chemicals such as vitamins In the absence of light, autooxidation is usually a slow process Compounds that can form a relatively stable C• radical upon H abstraction are especially susceptible to autooxidation. WHY? Consider the autooxidation of compounds with allylic or benzylic hydrogen atoms Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

11.9 Antioxidants Triglycerides are important to a healthy diet
Autooxidation can occur at the allylic positions causing the food to become rancid and toxic Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

11.9 Antioxidants Preservatives can undergo H abstraction to quench the C• radicals that form in the first step of autooxidation One molecule of BHT can prevent thousands of autooxidation reactions by stopping the chain reaction How does BHT’s structure make it good at taking on a free radical? Consider resonance and sterics Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

11.9 Natural Antioxidants Vitamins C is hydrophilic
Vitamin E is hydrophobic What parts of the body do these vitamins protect? For each vitamin, show its oxidation mechanism, and explain how that protects the body from autooxidation Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

11.10 Anti-Markovnikov Addition
We learned in chapter 9 that H-X will add across a C=C double bond with anti-Markovnikov regioselectivity when peroxides are present Now that we have discussed free radicals, we can explain the mechanism for the anti-Markovnikov addition Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

The Br• radical reacts to give the more stable C• radical A 3° radical forms through a lower TS than a 2° radical Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

Most of the radicals in solution at any given moment will be Br• radical. WHY? Give some examples of other termination steps that might occur but that would be less common Go back through each step in the mechanism to explain the ΔH value for each step Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

11.10 Addition Thermodynamics
Anti-Markovnikov radical addition of HBr is generally spontaneous (product favored) Yet, radical addition of HCl and HI are generally nonspontaneous (reactant favored) On the next few slides, we will examine the thermodynamics of each propagation step Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

Explain the sign (+/-) for the entropy term in each process Will the entropy change favor products or reactants? WHY? The enthalpy change is affected most by the relative stability of the two radical species Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

The HI reaction will never favor products. WHY? How can the temperature be adjusted to favor products for the HCl and HBr reaction? Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

For the second propagation step, why is the entropy term approximately zero? What small differences in entropy between products and reactants might account for entropy changes being slightly + or -? Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

For HCl , the second propagation step will not be product favored. WHY? HBr is the only reactant that favors product formation for both propagation steps Might the overall propagation involving HCl be product favored if the –ΔG of step 1 outweighs the +ΔG of step 2? Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

11.10 Addition Stereochemistry
Addition reactions often form a new chirality center Recall that at least 1 reagent in the reaction must be chiral for the reaction to be stereoselective Predicts the product distribution for the reaction below and explain the stereochemical outcome Practice with SkillBuilder 11.8 Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

11.11 Radical Polymerization
In chapter 9, we learned how some ionic polymerizations occur Free radical conditions are also frequently used to form polymers Recall that a polymerization process joins together many small units called monomers in a long chain Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

Radical polymerizations generally proceed through a chain reaction mechanism Note how the sum of the propagation steps yields the overall reaction Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

Radical polymerizations generally produce chains of monomers with a wide distribution of lengths How might experimental conditions be optimized to control the average length of the chains? Because the mechanism we just learned proceeds through 1° carbon free radical intermediates, it is usually not facile In chapter 27, we will discuss specialized catalysts that can be used to control such polymerization reactions Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

Branching is common in some radical polymerizations Branching makes polymer materials more flexible such as a polyethylene squeeze bottle When catalysts are used to minimize branching, more rigid materials are produced such as the squeeze bottle cap Why does branching affect rigidity? Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

11.12 Radical Petroleum Processes
Recall the cracking and reforming processes from chapters 4 and 8 Crude oil is cracked to produce smaller alkanes and alkenes Reforming increases branching. Propose a mechanism Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

11.13 Synthetic Utility of Halogenation
Radical chlorination and bromination are both useful processes Recall that bromination is more selective. WHY? Temperature can be used to help avoid polysubstitution. HOW? Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

Chlorination can be useful with highly symmetrical substrates It is difficult to avoid polysubstitution. WHY? The synthetic utility of halogenation is limited Chlorination is difficult to control Bromination requires a substrate with 1 site that is significantly more reactive than all others Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

Synthesizing a target molecule from an alkane is challenging because of its limited reactivity Often halogenation is the best option Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

Organic Chemistry Second Edition Chapter 11 David Klein

Similar presentations

Presentation on theme: "Organic Chemistry Second Edition Chapter 11 David Klein"— Presentation transcript:

Similar presentations

About project

Feedback

Log in

Auth with social network:

Organic Chemistry Second Edition Chapter 11 David Klein

Similar presentations

Presentation on theme: "Organic Chemistry Second Edition Chapter 11 David Klein"— Presentation transcript:

Similar presentations

About project

Feedback