Compounds with the structure ArNRNCONRNAr (where Ar represents an aromatic group) are

Rank the following radicals in order of stability: (a) (b)

Draw resonance structures for each of the following radicals: (a) (b) (c) (d)

The triphenylmethyl radical was the first radical to be observed. Draw all resonance structures of this radical and explain why this radical is unusually stable:

5-Methylcyclopentadiene undergoes homolytic bond cleavage of a C!H bond to form a radical that exhibits five resonance structures. Determine which hydrogen atom is abstracted and draw all five resonance structures of the resulting radical. Methylcyclopentadiene

Identify the weakest C!H bond in each of the following compounds: (a) (b) (c) (d)

The C!H bonds shown in red exhibit very similar BDEs, because homolytic cleavage of either bond results in a resonance-stabilized radical. Nevertheless, one of these C!H bonds is weaker than the other. Identify the weaker bond and explain your choice: Ha Hb

Draw the appropriate fishhook arrows for each of the following radical processes. HBr H + + Br (a) + Br (b) Br (c) + CH3 + + HBr (d) Br (e) + R R O O O O 2 R O O

Draw a mechanism for the following intramolecular process:

The triphenylmethyl radical reacts with itself to form the following dimer: 2 Identify the type of radical process taking place and draw the appropriate fishhook arrows. (Hint: It will help to draw just a few resonance structures of the triphenylmethyl radical.)

Draw a mechanism for each of the following processes: (a) Chlorination of methylene chloride to produce chloroform (b) Chlorination of chloroform to produce carbon tetrachloride (c) Chlorination of ethane to produce ethyl chloride (d) Chlorination of 1,1,1-trichloroethane to produce 1,1,1,2-tetrachloroethane (e) Chlorination of 2,2-dichloropropane to produce 1,2,2-trichloropropane

In practice, the chlorination of methane often produces many by-products. For example, ethyl chloride is obtained in small quantities. Can you suggest a mechanism for the formation of ethyl chloride?

Predict the major product obtained upon radical bromination of each of the following compounds: (a) (b) (c)

Compound A has molecular formula C5H12 and undergoes monochlorination to produce four different constitutional isomers. (a) Draw the structure of compound A. (b) Draw all four monochlorination products. (c) If compound A undergoes monobromination (instead of monochlorination), one product predominates. Draw that product.

Predict the stereochemical outcome of radical bromination of the following alkanes: (a) (b) (c) (d)

Compound A has molecular formula C5H11Br. When compound A is treated with bromine in the presence of UV light, the major product is 2,2-dibromopentane. Treatment of compound A with NaSH (a strong nucleophile) produces a compound with one chirality center having the R configuration. What is the structure of compound A?

Predict the products when each of the following compounds is treated with NBS and irradiated with UV light: (a) (b) (c) (d)

When 2-methyl-2-butene is treated with NBS and irradiated with UV light, five different monobromination products are obtained, one of which is a racemic mixture of enantiomers. Draw all five monobromination products and identify the product that is obtained as a racemic mixture.

Most supersonic planes produce exhaust of hot gases containing many compounds, including nitric oxide (NO). Nitric oxide is a radical that is believed to play a role in ozone depletion. Propose propagation steps that show how nitric oxide can destroy ozone in a chain process.

Compare the structure of vitamin E with the structures of BHT and BHA and then determine which hydrogen atom is most easily abstracted from vitamin E.

Predict the products for each reaction. In each case, be sure to consider whether a chirality center is being generated and then draw all expected stereoisomers. HBr (a) ROOR ? HBr (b) ROOR ? HBr (c) ROOR ? HBr (d) ROOR ? HBr (e) ROOR ? HBr (f) ROOR ?

The initiation step for radical addition of HBr is highly endothermic: h or heat RO OR RO OR H = +151 kJ/mol (a) Explain how this step can be thermodynamically favorable at high temperature even though it is endothermic. (b) Explain why this step is not thermodynamically favorable at low temperature.

Draw all resonance structures for each of the following radicals: (a) (b) (c) (d) (e)

Consider all of the different C!H bonds in cyclopentene and rank them in order of increasing bond strength: H H

Rank each group of radicals in order of increasing stability: (a) (b

Draw all resonance structures of the radical produced when a hydrogen atom is abstracted from the OH group in BHT: OH Butylated hydroxytoluene (BHT)

When isopropylbenzene (cumene) is treated with NBS and irradiated with UV light, only one product is obtained. Propose a mechanism and explain why only one product is formed. Br NBS h

There are three constitutional isomers with the molecular formula C5H12. Chlorination of one of these isomers yields only one product. Identify the isomer and draw the product of chlorination.

When ethylbenzene is treated with NBS and irradiated with UV light, two stereoisomeric compounds are obtained in equal amounts. Draw the products and explain why they are obtained in equal amounts. two products NBS h

AIBN is an azo compound (a compound with a NRN double bond) that is often used as a radical initiator. Upon heating, AIBN liberates nitrogen gas to produce two identical radicals: AIBN N N C C N N 2 + N2 C N (a) Give two reasons why these radicals are so stable. (b) Explain why the following azo compound is not useful as a radical initiator: N N

Triphenylmethane readily undergoes autooxidation to produce a hydroperoxide: Triphenylmethane (a) Draw the expected hydroperoxide. (b) Explain why triphenylmethane is so susceptible to autooxidation. (c) In the presence of phenol (C6H5OH), triphenylmethane undergoes autooxidation at a much slower rate. Explain this observation.

For each of the products shown in the following reaction, propose a mechanism that explains its formation: Br Br NBS h

Abstraction of a hydrogen atom from 3-ethylpentane can yield three different radicals, depending on which hydrogen atom is abstracted. Draw all three radicals and rank them in order of increasing stability

Identify the major product(s) for each of the following reactions. If any of the reactions do not yield a product, indicate no reaction. Br2 (a) h ? I2 (b) h ? Cl2 (c) h ? NBS h (d) ? NBS (e) h ? Br2 h (f)

Chlorination of (S)-2-chloropentane produces a mixture of isomers with molecular formula C5H10Cl2. How many isomers are obtained (consider stereoisomers as separate products)? Draw all of the products.

Predict the major product(s) obtained upon bromination of (S)-3-methylhexane.

Identify all products expected for each of the following reactions. Take stereochemistry into account and draw expected stereoisomer(s), if any: NBS (a) h ? NBS h (b) ?

Draw the propagation steps that achieve the autooxidation of diethyl ether to form a hydroperoxide: O Diethyl ether O OOH A hydroperoxide

Compound A has molecular formula C5H12, and monobromination of compound A produces only compound B. When compound B is treated with a strong base, a mixture is obtained containing compound C and compound D. Using this information, answer the following questions: (a) Draw the structure of compound A. (b) Draw the structure of compound B. (c) Draw the structures of compounds C and D. (d) When compound B is treated with potassium tert-butoxide, which product predominates: C or D? Explain your choice. (e) When compound B is treated with sodium ethoxide, which product predominates: C or D? Explain your choice.

Draw the products obtained when 3,3,6-trimethylcyclohexene is treated with NBS and irradiated with UV light.

When 2-methylpropane is treated with bromine in the presence of UV light, one product predominates. (a) Identify the structure of the product. (b) Draw the structure of the expected minor product. (c) Draw a mechanism for formation of the major product. (d) Draw a mechanism for formation of the minor product. (e) Using the mechanisms that you just drew, explain why we expect very little of the minor product.

Consider the structure of the following compound: (a) When this compound is treated with bromine under conditions that favor monobromination, two stereoisomeric products are obtained. Draw them and identify whether they are enantiomers or diastereomers. (b) When this compound is treated with bromine under conditions that favor dibromination, three stereoisomeric products are obtained. Draw them and explain why there are only three products and not four.

The rate at which two methyl radicals couple to form ethane is significantly faster than the rate at which two tert-butyl radicals couple. Offer two explanations for this observation.

How many constitutional isomers are obtained when each of the following compounds undergoes monochlorination? (a) (b) (c) (d) (e) (f) (g) (h) (i) (j)

Using acetylene and 2-methylpropane as your only sources of carbon atoms, propose a plausible synthesis for CH3COCH2CH(CH3)2. You will need to utilize many reactions from previous chapters.

Propose an efficient synthesis for each of the following transformations. You might find it useful to review Section 11.13 before attempting to solve these problems (a) (b) (c) (d) (e)

Consider the following two compounds. Monochlorination of one of these compounds produces twice as many stereoisomeric products as the other. Draw the products in each case and identify which compound yields more products upon chlorination.

When butane reacts with Br2 in the presence of Cl2, both brominated and chlorinated products are obtained. Under such conditions, the usual selectivity of bromination is not observed. In other words, the ratio of 2-bromobutane to 1-bromobutane is very similar to the ratio of 2-chlorobutane to 1-chlorobutane. Can you offer an explanation as to why we do not observe the normal selectivity expected for bromination?

When an acyl peroxide undergoes homolytic bond cleavage, the radicals produced can liberate carbon dioxide to form alkyl radicals: + CO2 R O O or h An acyl peroxide O R R O O O R Using this information, provide a mechanism of formation for each of the following products: O O O O

Consider the following radical process, called a thiol-ene coupling reaction, in which an alkene is treated with a thiol (RSH) in the presence of a radical initiator: R H S R R S R H H H H + Radical initiator Heat or light (a) Draw a plausible mechanism for this process, showing the initiation and propagation steps. (b) Biochemists have become increasingly interested in using organic reactions to modify proteins (Chapter 26) and study their behavior. The thiol-ene coupling reaction has recently been used to couple proteins together in an effort to elucidate the function of specific enzymes (J. Am. Chem. Soc., 2012, 134, 69166919). Predict the product that is expected when the following proteins undergo a thiol-ene coupling reaction: N O H S PROTEIN H PROTEIN

Commercial samples of pentacene (A) generally contain small amounts of impurities, including 6,13-dihydropentacene (B). Upon vacuum sublimation at high temperature (>300 C), a series of radical reactions are initiated leading to the formation of peripentacene (F) (J. Am. Chem. Soc. 2007, 129, 65366546). Several of the initial steps of a proposed mechanism of this conversion are shown below. Draw curved arrows consistent with the changes in bonding for each of the following steps: A + B S 2 C; C + C S D; C + A S E. + H 2 H A B C C A D E F

The alkyl halide 1-bromopropane is one of a number of compounds being considered as a replacement for chlorofluorocarbons as an industrial cleaning solvent. In a computational study of its atmospheric oxidation products, bromoacetone (structure below) was determined to be the major product (J. Phys. Chem. A 2008, 112, 79307938). The proposed mechanism involves four steps: (1) hydrogen abstraction by an OH radical, (2) formation of a peroxy radical by coupling with O2, (3) abstraction of an oxygen atom by NO, thus forming NO2 and an alkoxy radical, and (4) abstraction of a hydrogen atom by O2. Draw the mechanism that is consistent with this description. Br Br O + Other oxidized products

One strategy for the synthesis of complicated polycyclic ring systems involves radical-mediated cyclization processes. For example, when the following radical is generated, it undergoes a spontaneous cyclization to produce two new radicals (J. Am. Chem. Soc. 1986, 108, 17081709). Propose a plausible mechanism to account for the formation of each tricyclic ring system. CO2Et CN EtO2C CN CO2Et

Compounds with the structure ArNRNCONRNAr (where Ar represents an aromatic group) are used in liquid crystal formulations for LCDs (liquid crystal displays) as well as for optical switches and image storage because of their high resolution and sensitivity. However, it has been found recently that, upon irradiation with light at 350 nm, bisphenyl carbodiazone (PhNRNCONRNPh) undergoes homolytic decomposition to give radicals that can be trapped with a tetramethylpiperidinoxyl (TEMPO) radical (Tetrahedron Lett. 2006, 47, 21152118). Propose a mechanism that explains the formation of all three products from this process, shown below. N N N O N O N (TEMPO) Ph N N O O N + + O N Ph N2

As seen in this chapter, hydrocarbons typically do not undergo radical iodination in the presence of I2 (compound 2a). Furthermore, radical halogenation (even chlorination) of strained hydrocarbons, like cubane (1), is problematic if the reaction produces a halogen radical (X). An alternative method circumvents both of these issues by replacing the elemental halogen, X2, with a tetrahalomethane, CX4 (J. Am. Chem. Soc. 2001, 123, 18421847). The reaction is initiated by formation of a trihalomethyl radical, CX3. + + ZH 1 I I Z 2 3 4 2a: Z = I 2b: Z = CI3 4a: Z = I 4b: Z = CI3 (a) Propose a propagation cycle for the production of iodocubane (3) from cubane (1) and tetraiodomethane (2b). (b) Provide three possible termination steps. (c) The bond dissociation energy (BDE) for I!CI3 is 192 kJ/mol, while the BDE for H!CI3 is 423 kJ/mol. Using this information, provide a thermodynamic argument that explains why 2b is an effective iodination reagent while 2a is not.

Resveratrol is a naturally occurring antioxidant found in a broad range of plants including grapes, mulberries, and peanuts. It demonstrates useful activity against heart disease and cancer. In the presence of an alkoxy radical (RO), a hydrogen atom is abstracted from resveratrol (J. Org. Chem. 2009, 74, 50255031). Predict which hydrogen atom is preferentially abstracted and justify your choice. HO HO OH Resveratrol

In Chapter 2, we saw several patterns for drawing resonance structures of ions or uncharged compounds. There are also several patterns for drawing resonance structures of radicals, although we have only encountered one such pattern (allylic or benzylic radicals). One other pattern is characterized by a lone pair on an atom that is adjacent to an atom with an unpaired electron, as seen in the following example. The unpaired electron is delocalized by resonance, with radical character being spread over the nitrogen and phosphorus atoms. Note that phosphorus is a third-row element, so it can have more than eight electrons. We will make use of a related pair of resonance structures in this problem. N P N P The rearrangement shown below (Ar = aromatic group) represents the conversion of a sulfenate to a sulfoxide, which is initiated by heat. The transformation is believed to occur via a two-step process in which the C!O bond undergoes homolytic cleavage followed by a recombination of the resulting radicals to form the product (J. Am. Chem. Soc. 2000, 122, 33673374): O S Ar S Ar Heat O (a) Draw a mechanism of this rearrangement, consistent with the description provided. (b) Provide a reasonable rationalization for the fact that the C!O bond is cleaved preferentially over the O!S bond in the first step of the mechanism.

Compound 2 was used as a key intermediate in a synthesis of oseltamivir, an anti-influenza agent (J. Am. Chem. Soc. 2006; 128, 63106311). Propose a plausible mechanism for the conversion of 1 to 2, as shown, and explain the stereochemical outcome: N O R I N O R Br 1 2 1) t-BuOK 2) NBS, h

The Kharasch reaction is a radical process in which carbon tetrachloride is added across an alkene: R R Cl CCl3 O O Ph O Ph O Heat CCl4 (a) Draw a mechanism showing initiation and propagation steps for this reaction and explain the observed regiochemical outcome. (b) A variation of the Kharasch reaction was employed during a synthesis of a key piece of paclitaxel, an anticancer agent used in the treatment of breast cancer (Tetrahedron Lett. 2002, 43, 85878590). Propose a plausible mechanism (initiation and propagation steps) for this ring-closure reaction, shown here: O OH O O HO CCl4 (PhCOO)2 heat O O O HO OH Cl3C Cl

The ring-forming reaction below (initiated by heat) is believed to undergo a stepwise radical mechanism via the intermediate diradical shown (J. Am. Chem. Soc. 2009, 131, 653661). Propose a reasonable mechanism to account for the formation of the product from the intermediate diradical. N O N O N OH