For each of the following compounds, draw its structure: (a) 2,6-Dibromo-4-chloroanisole

Provide a systematic name for each of the following compounds: H O (a) CH3 Br (b) O2N NO2 (c) OH (d) OH Br Br (e) Cl

Aromatic compounds often have multiple names that are all accepted by IUPAC. Provide three different systematic (IUPAC) names for the following compound: Br CH3 OH

For each of the following compounds, draw its structure: (a) 2,6-Dibromo-4-chloroanisole (b) meta-Nitrophenol

Provide at least five different acceptable IUPAC names for the following compound:

In Chapter 9, we saw that meta-chloroperoxybenzoic acid (MCPBA) is a peroxy acid commonly used to convert alkenes into epoxides. Recall that peroxy acids have the following structure: R O O O H (a) Draw the structure of MCPBA. (b) Provide a systematic name for the compound formed by replacing the chlorine atom in MCPBA with a methyl group.

Compound A is an aromatic compound with molecular formula C8H8. When treated with excess Br2, compound A is converted into compound B, with molecular formula C8H8Br2. Identify the structures of compounds A and B. Compound a b Compound B (C8h8) (C8h8Br2)

In some circumstances, dehydrogenation is observed. Dehydrogenation involves the loss of two hydrogen atoms (the reverse of hydrogenation). Analyze each of the following dehydrogenation reactions and then use the information in Figure 18.1 to predict whether each transformation will be downhill in energy (negative value for DH) or uphill in energy (positive value for DH). H2 (a) + 2 H2 (b) + H2 (c) +

Predict whether each of the following compounds should be aromatic: (a) (b) (c)

The cyclopropenyl cation has a three-membered ring that contains a continuous system of overlapping p orbitals. This system contains a total of two p electrons. Using a Frost circle, draw an energy diagram showing the relative energy levels of all three MOs and then predict whether this cation is expected to exhibit aromatic stabilization. !

Predict whether the following compound will be aromatic, nonaromatic, or antiaromatic. Explain your reasoning.

Determine whether each of the following ions is aromatic, nonaromatic, or antiaromatic: (a) @ (b) ! (c) ! (d) @

Explain the vast difference in pKa values for the following two apparently similar compounds: pKa 16 pKa 36

Predict which compound will react more readily in an SN1 process and explain your choice: Br Br

Identify which of the following compounds is more acidic and explain your choice:

For each of the following compounds determine which (if any) lone pairs are participating in aromaticity: (a) O (b) S (c) N H (d) N S O (e) ! N N H NH2 Histamine N N H NH2 N N (f) O O (g) N

Go to the beginning of Section 18.1 where eight best-selling drugs were shown. Review the structures of those compounds and identify all of the aromatic rings that are not already highlighted in red.

Identify which compound is expected to have a lower pKa. Justify your choice. N N H H H ! !

Meclizine, shown below, is an antiemetic (prevents nausea and vomiting). (a) Would you expect meclizine to be an antihistamine as well? Justify your answer. (b) This drug is known to cause sedation. Describe the source of the sedative properties of meclizine. (c) Can you suggest a structural modification that could poss bly modify the sedative properties of meclizine? Meclizine

Draw the expected product when each of the following compounds is treated with chromic acid: (a) (b) (c)

Propose an efficient synthesis for each of the following transformations: (a) OH (b) N (c) O (d)

Propose an efficient synthesis for the following transformation:

Starting with isopropyl benzene, propose a synthesis for acetophenone. (Hint: Make sure to count the number of carbon atoms in the starting material and product.)

Propose an efficient synthesis for the following transformation: OH

Predict the major product obtained when each of the following compounds is treated with Birch conditions: (a) (b) (c) (d) OH O (e) HO O (f)

Consider the structure of anisole (also called methoxybenzene). In the next chapter, we will discuss whether a methoxy group is electron donating or electron withdrawing. We will see that there is a competition between two factors. Specifically, we will see that the methoxy group is electron withdrawing because of induction, but it is electron donating because of resonance. (a) Draw the resonance structures of anisole. (b) Whenever resonance and induction compete with each other, resonance is generally the dominant factor. Using this information, predict the regiochemical outcome of a Birch reduction of anisole.

A compound with molecular formula C8H8O produces an IR spectrum with signals at 3063, 1686, and 1646 cm-1 . The 1 H NMR spectrum of this compound exhibits a singlet at 2.6 ppm (I=3H) and a multiplet at 7.5 (I=5H). (a) Draw the structure of this compound. (b) What is the common name of this compound? (c) When this compound is treated with Na, CH3OH, and NH3, a reduction takes place, giving a new compound with molecular formula C8H10O. Draw the product of this reaction.

A compound with molecular formula C8H10 produces an IR spectrum with many signals, including 3108, 3066, 3050, 3018, and 1608 cm-1 . The 1 H NMR spectrum of this compound exhibits a singlet at 2.2 ppm (I=6H) and a multiplet at 7.1 ppm (I=4H). The 13C NMR spectrum of this compound exhibits signals at 19.7, 125.9, 129.6, and 136.4 ppm. (a) Draw the structure of this compound. (b) What is the common name of this compound? (c) Treating this compound with chromic acid yields a product with molecular formula C8H6O4. Draw the product of this reaction.

Provide a systematic name for each of the following compounds: OH O (a) OH Br (b) O Cl 2N (c) OH Br H O O2N (d) (e)

Draw a structure for each of the following compounds: (a) ortho-Dichlorobenzene (b) Anisole (c) meta-Nitrotoluene (d) Aniline (e) 2,4,6-Tribromophenol (f) para-Xylene

Draw structures for the eight constitutional isomers with molecular formula C9H12 that contain a benzene ring.

Draw structures for all constitutional isomers with molecular formula C8H10 that contain an aromatic ring.

Draw all aromatic compounds that have molecular formula C8H9Cl.

The systematic name of TNT, a well-known explosive, is 2,4,6-trinitrotoluene (as seen in SkillBuilder 18.1). There are only five constitutional isomers of TNT that contain an aromatic ring, a methyl group, and three nitro groups. Draw all five of these compounds and provide a systematic name for each.

Identify the number of p electrons in each of the following compounds: (a) @ (b) S (c) (d) N (e) !

Students often confuse cyclohexane and benzene. Cyclohexane Benzene In fact, these compounds have different properties, different geometry, and different reactivity. Each of these compounds also has a unique set of terminology. For each of the following terms, identify whether it is used in reference to benzene or to cyclohexane: (a) meta (b) Frost circle (c) sp2 (d) Chair (e) ortho (f) sp3 (g) Resonance (h) p Electrons (i) para (j) Ring flip (k) Boat

Identify which of the following compounds are aromatic: (a) (b) O O O (c) O N (d) (e) !

Firefly luciferin is the compound that enables fireflies to glow. N HO S N S OH O Firefly luciferin (a) The structure exhibits three rings. Identify which of the rings are aromatic. (b) Identify which lone pairs are participating in resonance.

Identify each of the following compounds as aromatic, nonaromatic, or antiaromatic. Explain your choice in each case. O (a) (b) N H N S (c) N N (d) (e) N ! H N H (f) H ! (g) O H ! N N (h)

Consider the structures of the following alkyl chlorides: O Cl Cl Cl (a) Which compound would you expect to undergo an SN1 process most readily? Justify your choice. (b) Which compound would you expect to undergo an SN1 process least readily? Justify your choice.

Which of the following compounds would you expect to be most acidic? Justify your choice. O

Identify which of the following compounds is expected to be a stronger base. Justify your choice. N N

Draw a Frost circle for the following cation and explain the source of instability of this cation: !

Do you expect the following dianion to exhibit aromatic stabilization? Explain. @ @

Would you expect the following compound to be aromatic? Justify your answer. N N O OR

Diphenylmethane exhibits two aromatic rings, which achieve coplanarity in the highest energy conformation. Explain. Diphenylmethane

The following two drawings are resonance structures of one compound: But the following two drawings are not resonance structures: Not resonance structures They are, in fact, two different compounds. Explain.

Predict the major product of the following reactions. NBS (a) Heat or light ? Na2Cr2O7 H2SO4 (b) , H2O ? HO H2SO4 (c) Heat ? Br NaOEt (d) ?

How many signals do you expect in the 13C NMR spectrum of each of the following compounds? (a) (b) Br (c) (d)

Predict the product of the following reaction and propose a mechanism for its formation: Na, CH3OH NH3 ?

One of the constitutional isomers of xylene was treated with sodium, methanol, and ammonia to yield a product that exhibited five signals in its 13C NMR spectrum. Identify which constitutional isomer of xylene was used as the starting material.

Consider the following two compounds: How would you distinguish between them using: (a) IR spectroscopy? (b) 1 H NMR spectroscopy? (c) 13C NMR spectroscopy?

Explain how the following two compounds can have the same conjugate base. Is this conjugate base aromatic?

Compare the electrostatic potential maps for cycloheptatrienone and cyclopentadienone. Cycloheptatrienone Cyclopentadienone O O Both of these maps were created using the same color scale so they can be compared. Notice the difference between the oxygen atoms in these two compounds. There is more partial negative character on the oxygen in the first compound (cycloheptatrienone). Can you offer an explanation for this difference?

Azulene exhibits an appreciable dipole moment, and an electrostatic potential map indicates that the five-membered ring is electron rich (at the expense of the seven-membered ring). Azulene (a) In Chapter 2, we saw that a resonance structure will be insignificant if it has carbon atoms with opposite charges (C- and C+). Azulene represents an exception to this rule, because some resonance structures (with C- and C+) exhibit aromatic stabilization. With this in mind, draw resonance structures of azulene and use them to explain the observed dipole moment. (b) Based on your explanation, determine which compound is expected to exhibit a larger dipole moment.

Propose an efficient synthesis for the following transformation: Br

Propose a plausible mechanism for the following transformation: OH Cl HCl

Identify the structure of a compound with molecular formula C9H10O2 that exhibits the following spectral data: (a) IR: 3005 cm-1 , 1676 cm-1 , 1603 cm-1 (b) 1 H NMR: 2.6 ppm (singlet, I = 3H), 3.9 ppm (singlet, I = 3H), 6.9 ppm (doublet, I = 2H), 7.9 ppm (doublet, I = 2H) (c) 13C NMR: 26.2, 55.4, 113.7, 130.3, 130.5, 163.5, 196.6 ppm

Propose an efficient synthesis for each of the following transformations: H O (a) O (b) OH OH (c) (d)

A compound with molecular formula C11H14O2 exhibits the following spectra (1 H NMR, 13C NMR, and IR). Identify the structure of this compound. Proton NMR Carbon NMR 9 1 2 2 180 160 140 120 100 80 20 0 11 12345678910 60 40 Chemical Shift (ppm) Chemical Shift (ppm) 125.2 30.9 130.4 172.6 157.4 34.7 126.5 Wavenumber (cm1)

A compound with molecular formula C9H10O exhibits the following spectra (1 H NMR, 13C NMR, and IR). Identify the structure of this compound. Proton NMR Carbon NMR 2 5 1 2 200 180 160 140 120 100 80 60 40 20 10 9 8 7 6 5 4 3 2 Chemical Shift (ppm) Chemical Shift (ppm) 201.5 126.4 140.7 128.6 45.2 25.1 128.5 Wavenumber (cm1 )

Below are two hypothetical compounds. N O N N N (a) Which compound would you expect to hold greater promise as a potential antihistamine? Explain your choice. (b) Do you expect the compound you chose [in part (a)] to exhibit sedative properties? Explain your reasoning.

Would you expect the following compound to be aromatic? Explain your answer. O

Compounds A, B, C, and D are constitutionally isomeric, aromatic compounds with molecular formula C8H10. Deduce the structure of compound D using the following clues: The 1 H NMR spectrum of compound A exhibits two upfield signals as well as a multiplet near 7 ppm (with I=5). The 13C NMR spectrum of compound B exhibits four signals. The 13C NMR spectrum of compound C exhibits only three signals.

The following two compounds each exhibit two heteroatoms (one nitrogen atom and one oxygen atom): N O Compound A N O Compound B In compound A, the lone pair on the nitrogen atom is more likely to function as a base. However, in compound B, a lone pair on the oxygen atom is more likely to function as a base. Explain this difference.

Propose an efficient synthesis for the following transformation: CH3 O CH3 CH

Using toluene and acetylene as your only sources of carbon atoms, show how you would prepare the following compound: O

Due to their potential application in organic electronic devices, such as television screens, a large number of compounds containing quinoidal pi systems (such as compound A) have been prepared. Reduction of A gives B, as shown (Tetrahedron Lett. 2012, 53, 5385 5388): NC CN NC CN A 2e@ NC CN NC CN B @ @ (a) Determine whether the 14-membered ring in B is aromatic. (b) Draw resonance structures showing how the negative charges in B are delocalized. (c) Draw at least three resonance structures that demonstrate the delocalized nature of the unpaired electrons in B.

Compound 1 contains a tetrazole ring (a five-membered ring containing four nitrogen atoms), while its constitutional isomer, compound 2, exhibits an azido group (!N3). There is evidence that compounds 1 and 2 rapidly interconvert, and exist in equilibrium with one another (J. Am. Chem. Soc. 1959, 81, 46714673). Of the four nitrogen atoms in these compounds, only one of them remains incorporated in a ring in compound 2. Determine whether this nitrogen atom undergoes a change in hybridization state as a result of the isomerization process. Explain. S N N N N S N N N N 1 2 ! @

Studies modeling chemical reactions in the atmosphere of Saturns moon Titan suggest that the compound 1,2,5,6-tetracyanocyclooctatetraene can form through one of a series of gas-phase reactions mediated by monocationic magnesium (Mg+ ). This organic compound forms a complex in which the lone pairs on all four nitrogen atoms interact with a single Mg+ ion (J. Am. Chem. Soc. 2005, 127, 1307013078). (a) Sketch the structure of this complex as described. Use dotted lines to show the interactions between the lone pairs and the magnesium ion. (b) Explain why 1,2,4,5-tetracyanobenzene would not be able to form a comparable complex.

Consider the structures for naphthalene and phenanthrene. 1 2 3 45 6 7 8 9 10 1 2 3456 7 8 9 10 Naphthalene Phenanthrene (a) Draw all three resonance structures of naphthalene and then explain why the C2!C3 bond has a longer bond length (1.42 ) than the C1!C2 bond (1.36 ). (b) The difference in bond lengths, called bond fixation, is very pronounced in phenanthrene. Draw all five resonance structures of phenanthrene and then use those resonance structures to predict which bond is expected to exhibit the shortest bond length. (c) Treatment of phenanthrene with Br2 affords a compound with molecular formula C14H10Br2 (J. Am. Chem. Soc. 1985, 107, 6678 6683). Draw the structure of this product.

Cyclobutadiene is not stable at room temperature. Upon formation, it rapidly dimerizes via a Diels-Alder reaction. However, several derivatives of cyclobutadiene are known to be stable at room temperature (Angew Chem. Int. Ed. 1988, 27, 14371455): R1 R2 R4 R3 (a) One such derivative is tri-tert-butylcyclobutadiene (R1=R2=R3= t-Bu; R4=H). Suggest an explanation for why this compound is stable. (b) Another stable derivative of cyclobutadiene has been prepared in which R1=R3=NEt2 and R2=R4=CO2Et. Suggest an explanation for why this compound is stable. (c) In part (b), we saw that cyclobutadiene is stabilized by the presence of neighboring NEt2 and CO2Et groups. In contrast, the presence of these two groups has a destabilizing effect on systems with 4n+2 p electrons. Explain this observation.

When the following cyclopentadiene-fused [14]annulene is treated with KH, a green solution of a stable cyclopentadiene anion results. This transformation causes a dramatic change in part of the 1 H NMR spectrum: the methyl groups shift from -3.9 ppm to -1.8 ppm (J. Org. Chem. 2004, 69, 549554). Provide an explanation for this observation. t-Bu t-Bu t-Bu t-Bu KH @

The following compound, isolated from a New Zealand sea squirt, demonstrates activity against a malarial strain that is resistant to other treatments (J. Nat. Prod. 2011, 74, 19721979). Consider the relative basicity of each nitrogen atom in this structure and draw the product expected when this compound is treated with two equivalents of a strong acid (e.g., HCl). N N N H H Br NH2

In a mass spectrometric study of nitrogenous aromatic compounds, a peak at m/z = 39 was found for 17 of the 20 compounds investigated, including the 4 compounds in the first row below, with a relative intensity ranging from 5 to 84% of the base peak. This peak was absent in the mass spectrum of each of the three compounds in the bottom row (J. Org. Chem. 1964, 29, 20652066). Propose a structure for the cationic fragment with m/z = 39 and an explanation consistent with the information provided. N N N N N HN HN HN HN N N NH2 NH2 N N N H2N

Fluorenyldiene 1 is a highly conjugated, planar molecule that is readily oxidized to dication 2 (J. Org. Chem. 2002, 67, 7029 7036). 1 2 ! ! 2e (a) Draw at least four other resonance structures of dication 2 and identify why the resonance structure shown here is the greatest contributor to the overall resonance hybrid, despite the presence of neighboring like charges (which is generally a destabilizing factor). (b) Explain why the lowest energy conformation for 2 is not planar and instead exhibits a perpendicular arrangement between the two ring systems.

Numerous herbicides and fungicides are known to contain an acetylenic group. For example, compound A is a pyrimidinone herbicide that functions by inhibiting the accumulation of both chlorophyll and b-carotene. During a synthesis of A, shown below, an inactive product was also formed (compound B) which was found to be a constitutional isomer of A, also containing an acetylenic group. The ratio of A:B was 1:4 (Bioorg. Med. Chem. 2009, 17, 40474063). NHN F3C O NN F3C O A B HC CCH2Br NaOMe + (a) Draw a plausible mechanism for the formation of compound A. (b) Draw the likely structure of compound B and provide a mechanism for its formation. (c) Explain why B is favored over A in this process.