Cycloserine is an antibiotic isolated from the microbe Streptomyces orchidaceous. It is

Draw a Lewis structure for each of the compounds below: (a) \(\mathrm{CH}_{2}=\mathrm{CHOCH}_{2} \mathrm{CH}\left(\mathrm{CH}_{3}\right)_{2}\) (b) \(\left(\mathrm{CH}_{3} \mathrm{CH}_{2}\right)_{2} \mathrm{CHCH}_{2} \mathrm{CH}_{2} \mathrm{OH}\) (c) \(\left(\mathrm{CH}_{3} \mathrm{CH}_{2}\right)_{3} \mathrm{COH}\) (d) \(\left(\mathrm{CH}_{3}\right)_{2} \mathrm{C}=\mathrm{CHCH}_{2} \mathrm{CH}_{3}\) (e) \(\mathrm{CH}_{2}=\mathrm{CHCH}_{2} \mathrm{OCH}_{2} \mathrm{CH}\left(\mathrm{CH}_{3}\right)_{2}\) (f) \(\left(\mathrm{CH}_{3} \mathrm{CH}_{2}\right)_{2} \mathrm{C}=\mathrm{CH}_{2}\) (g) \(\left(\mathrm{CH}_{3}\right)_{3} \mathrm{CCH}_{2} \mathrm{CH}_{2} \mathrm{OH}\) (h) \(\mathrm{CH}_{3} \mathrm{CH}_{2} \mathrm{CH}_{2} \mathrm{CH}_{2} \mathrm{CH}_{2} \mathrm{CH}_{3}\) (i) \(\mathrm{CH}_{3} \mathrm{CH}_{2} \mathrm{CH}_{2} \mathrm{OCH}_{3}\) (j) \(\left(\mathrm{CH}_{3} \mathrm{CH}_{2} \mathrm{CH}_{2}\right)_{2} \mathrm{CHOH}\) (k) \(\left.\mathrm{CH}_{3} \mathrm{CH}_{2}\right)_{2} \mathrm{CHCH}_{2} \mathrm{OCH}_{3}\) (l) \(\left(\mathrm{CH}_{3}\right)_{2} \mathrm{CHCH}_{2} \mathrm{OH}\)

Identify which two compounds below are constitutional isomers: (CH3)3COCH3 (CH3)2CHOCH3 (CH3)2CHOCH2CH3

Identify the number of sp3 -hybridized carbon atoms in the following compound: (CH3)2CRCHC(CH3)3

Cyclopropane (shown below) has only one constitutional isomer. Draw a condensed structure of that isomer. H2C H2C CH2

For each of the following molecules, determine the number of carbon atoms present and then determine the number of hydrogen atoms connected to each carbon atom: (a) (b) O N H (c) (d) (e) OH O (f) O (g) O (h) OH (i) (j) (k) O (l) O

Each transformation below shows a starting material being converted into a product (the reagents necessary to achieve the transformation have not been shown). For each transformation, determine whether the product has more carbon atoms, fewer carbon atoms, or the same number of carbon atoms as the starting material. In other words, determine whether each transformation involves an increase, decrease, or no change in the number of carbon atoms. (a) O (b) O O (c) OH (d) O O HO OH

Identify whether each transformation below involves an increase, a decrease, or no change in the number of hydrogen atoms: (a) (b)

Draw a bond-line structure for each of the following compounds: (a) C C C H H H H H H H C H H C C H H H C H H H C H H H (b) O H C H C H H H C H H C C H H H (c) OH HO C OH C C H H H H H (d) (CH3)3C!C(CH3)3 (e) CH3CH2CH(CH3)2 (f) (CH3CH2)3COH (g) (CH3)2CHCH2OH (h) CH3CH2CH2OCH3 (i) (CH3CH2)2CRCH2 (j) CH2RCHOCH2CH(CH3)2 (k) (CH3CH2)2CHCH2CH2NH2 (l) CH2RCHCH2OCH2CH(CH3)2 (m) CH3CH2CH2CH2CH2CH3 (n) (CH3CH2CH2)2CHCl (o) (CH3)2CRCHCH2CH3 (p) (CH3CH2)2CHCH2OCH3 (q) (CH3)3CCH2CH2OH (r) (CH3CH2CH2)3COCH2CH2CHRCHCH2CH2OC(CH2CH3)3

Draw bond-line structures for all constitutional isomers of the following compound: CH3CH2CH(CH3)2

In each of the following compounds, identify all carbon atoms that you expect will be deficient in electron density (d+). If you need help, refer to Section 1.5. (a) O Br H (b) O O (c)

Atenolol and enalapril are drugs used in the treatment of heart disease. Both of these drugs lower blood pressure (albeit in different ways) and reduce the risk of heart attack. Using Table 2.1, identify and label all functional groups in these two compounds: Atenolol Enalapril

For each of the following structures determine whether any of the nitrogen atoms bear a formal charge: (a) N (b) N (c) N (d) N

For each of the following structures determine whether any of the oxygen atoms bear a formal charge: (a) O (b) O (c) O (d) O H H

Draw all lone pairs on each of the oxygen atoms in the following structures. Before doing this, review Table 2.2 and then come back to these problems. Try to identify all lone pairs without having to count. Then, count to see if you were correct. (a) O (b) O O (c) OH O (d) O O @ (e) O@ (f) O (g) O H ! (h) O H H H ! (i) O O O ! @ (j) O O H H R

A carbene is a highly reactive intermediate in which a carbon atom bears a lone pair and no formal charge: How many hydrogen atoms are attached to the central carbon atom above?

Draw all lone pairs on each of the nitrogen atoms in the following structures. First, review Table 2.3 and then come back to these problems. Try to identify all lone pairs without having to count. Then, count to see if you were correct. (a) N (b) N H (c) N (d) N! (e) N @ (f) N (g) N ! (h)

Each of the following structures contains both oxygen and nitrogen atoms. Identify all lone pairs associated with those atoms. ! H (b) O C N @ (c) O N O ! (d) N O ! O @ (e) NH2 O (f) O C N

Identify the number of lone pairs in each of the following structures: (a) @ (b) ! (c) @ (d) O O @

Amino acids are biological compounds with the following structure, where the R group can vary. The structure and biological function of amino acids will be discussed in Chapter 25. Identify the total number of lone pairs present in an amino acid, assuming that the R group does not contain any atoms with lone pairs.(a) O N ! H (b) O C N @ (c) O N O ! (d) N O ! O @ (e) NH2 O (f) O C N @ O NH3 O R An amino acid

Troglitazone, rosiglitazone, and pioglitazone, all antidiabetic drugs introduced to the market in the late 1990s, are believed to act on the same receptor: Troglitazone S N O O H O O HO Rosiglitazone S N O O H O N N Pioglitazone S N O O H O N (a) Based on these structures, try to identify the likely pharmacophore that is responsible for the antidiabetic activity of these drugs. (b) Consider the structure of rivoglitazone (below). This compound is currently being studied for potential antidiabetic activity. Based on your analysis of the likely pharmacophore, do you believe that rivoglitazone will exhibit antidiabetic properties? Rivoglitazone

For each of the problems below, determine whether each curved arrow violates either of the two rules and describe the violation, if any. (Dont forget to count all hydrogen atoms and all lone pairs.) (a) N H H ! (b) O (c) OH (d) O H (e) O H (f) (g) (h) O (i) N C (j) H3C N N ! (k) O R (l) N

Drawing the resonance structure of the following compound requires one curved arrow. The head of this curved arrow is placed on the oxygen atom, and the tail of the curved arrow can only be placed in one location without violating the rules for drawing curved arrows. Draw this curved arrow. O

For each of the structures below, draw the resonance structure that is indicated by the curved arrows. Be sure to include formal charges. (a) ! (b) @ (c) O O (d) N @ (e) OH (f) O O N ! @ (g) O O N ! @ (h) O

In each case below, draw the curved arrow(s) required in order to convert the first resonance structure into the second resonance structure. In each case, begin by drawing all lone pairs and then use the formal charges to guide you. (a) O O ! @ (b) O O ! @ (c) N O O N @ @ (d) ! !

For each of the compounds below, locate the pattern we just learned (lone pair next to a p bond) and draw the appropriate resonance structure: (a) O O (b) @ (c) O (d) NH2 (e) O N O @ ! (f) O@ (g) N Acetylcholine (a neurotransmitter) O O ! (h) 5-Amino-4-oxopentanoic acid (used in therapy and diagnosis of hepatic tumors)

Draw the resonance structure(s) for each of the compounds below: (a) ! (b) ! (c) ! (d)

For each of the compounds below, locate the lone pair adjacent to a positive charge and draw the resonance structure: (a) N ! (b) N @ ! (c) O !

Draw a resonance structure for each of the compounds below. (a) N (b) O (c)

Draw a resonance structure of the compound below, which was isolated from the fruits of Ocotea corymbosa, a native plant of the Brazilian Cer

Draw a resonance structure of the compound shown below, called 2-heptanone, which is found in some kinds of cheese.

Fingolimod is a novel drug that has recently been developed for the treatment of multiple sclerosis. In April of 2008, researchers reported the results of phase III clinical trials of fingolimod, in which 70% of patients who took the drug daily for three years were relapse free. This is a tremendous improvement over previous drugs that only prevented relapse in 30% of patients. Draw a resonance structure of fingolimod: Fingolimod H2N HO OH

Draw resonance structures for each of the following compounds: (a) O (b) ! (c) @ (d) O O (e) O ! (f) O (g) N ! (h) N (i) N O (j) Cl

Draw all significant resonance structures for each of the following compounds: (a) N H (b) N (c) N@ (d) O C N (e) S O (f) @ (g) O (h) ! (i) O @ (j) C N @ (k) C N (l) OH !

Use resonance structures to help you identify all sites of low electron density (d+) in the following compound: Step 2 Identify if the resonance structure is significant by inspecting the number of charges and the number of electrons on heteroatoms. Step 3 Repeat steps 1 and 2 to identify any other significant resonance structures. O

Use resonance structures to help you identify all sites of high electron density (d-) in the following compound: OH

For each compound below, identify all lone pairs and indicate whether each lone pair is localized or delocalized. Then, use that information to determine the hybridization state and geometry for each atom that exhibits a lone pair. (a) H2N NH2 (b) O N O (c) O OH H2N NH2 (d) N (e) N H (f) O O

Nicotine is a toxic substance present in tobacco leaves. Nicotine N N There are two lone pairs in the structure of nicotine. In general, localized lone pairs are much more reactive than delocalized lone pairs. With this information in mind, do you expect both lone pairs in nicotine to be reactive? Justify your answer.

Isoniazid is used in the treatment of tuberculosis and multiple sclerosis. Identify each lone pair as either localized or delocalized. Justify your answer in each case. Isoniazid N N O NH2 H

Draw all carbon atoms, hydrogen atoms, and lone pairs for the following compounds: O OH O O HO N O H Caffeine N N N N O O Acetaminophen (Tylenol) Acetylsalicylic acid (aspirin)

Draw bond-line structures for all constitutional isomers of C4H10.

Draw bond-line structures for all constitutional isomers of C5H12.

Draw bond-line structures for vitamin A and vitamin C: Vitamin A C C C C C C C C C C C C C C C C C C C O H H H H H H H H C H H H H H H H H H H H H H H H H H H H H H H Vitamin C C C C O C HO OH C O C HO HO H H H H

How many lone pairs are found in the structure of vitamin C?

Identify the formal charge in each case below: O N N O O N

Draw significant resonance structures for the following compound: O

Learning to extract structural information from molecular formulas: (a) Write out the molecular formula for each of the following compounds: Compare the molecular formulas for the above compounds and fill in the blanks in the following sentence: The number of hydrogen atoms is equal to __________ times the number of carbon atoms plus __________. (b) Now write out the molecular formula for each of these compounds: Each of the compounds above has either a double bond or a ring. Compare the molecular formulas for each of these compounds. In each case, the number of hydrogen atoms is __________ times the number of carbon atoms. Fill in the blank. (c) Now write out the molecular formula for each of these compounds: Each of the compounds above has either a triple bond or two double bonds or two rings or a ring and a double bond. Compare the molecular formulas for each of these compounds. In each case, the number of hydrogen atoms is __________ times the number of carbon atoms minus __________. Fill in the blanks. (d) Based on the trends above, answer the following questions about the structure of a compound with molecular formula C24H48. Is it possible for this compound to have a triple bond? Is it possible for this compound to have a double bond? (e) Draw all constitutional isomers that have the molecular formula C4H8.

Each compound below exhibits one lone pair. In each case, identify the type of atomic orbital in which the lone pair is contained. (a) N ! (b) @ (c) N !

Draw all significant resonance structures for each of the following compounds: (a) N OH H ! (b) O ! (c) !

Write a condensed structural formula for each of the following compounds: (a) (b) OH (c)

What is the molecular formula for each compound in the previous problem?

Which of the following drawings is not a resonance structure for 1-nitrocyclohexene? Explain why it cannot be a valid resonance structure. (a) O N ! O @ (b) N O ! O@ (c) N O O ! ! @ @ (d) N O

Identify the number of carbon atoms and hydrogen atoms in the compound below:

Identify any formal charges in the following structures: (a) O (b) N N (c) O (d) N

Draw bond-line structures for all constitutional isomers with molecular formula C4H9Cl.

Draw resonance structures for each of the following: (a) O (b) O ! (c) ! (d) N (e) NH2 (f) @ (g) O (h) O O (i) OH ! (j)

Determine the relationship between the two structures below. Are they resonance structures or are they constitutional isomers? O O @

Consider each pair of compounds below and determine whether the pair represent the same compound, constitutional isomers, or different compounds that are not isomeric at all: (a) (b) (c) (d)

Draw a bond-line structure for each of the following compounds: (a) CH2RCHCH2C(CH3)3 (b) (CH3CH2)2CHCH2CH2OH (c) CH#COCH2CH(CH3)2 (d) CH3CH2OCH2CH2OCH2CH3 (e) (CH3CH2)3CBr (f) (CH3)2CRCHCH3

A mixture of sulfuric acid and nitric acid will produce small quantities of the nitronium ion (NO2 +): O N O ! Does the nitronium ion have any significant resonance structures? Why or why not?

Consider the structure of ozone: O O O @ ! Ozone is formed in the upper atmosphere, where it absorbs shortwavelength UV radiation emitted by the sun, thereby protecting us from harmful radiation. Draw all significant resonance structures for ozone. (Hint: Begin by drawing all lone pairs.)

Melatonin is an animal hormone believed to have a role in regulating the sleep cycle: The structure of melatonin incorporates two nitrogen atoms. What are the hybridization state and geometry of each nitrogen atom? Explain your answer. Melatonin N N O O

Draw all significant resonance structures for each of the following compounds: Estradiol (Female sex hormone) Testosterone (Male sex hormone) HO OH H H H O OH H H H

Cycloserine is an antibiotic isolated from the microbe Streptomyces orchidaceous. It is used in conjunction with other drugs for the treatment of tuberculosis. Cycloserine O N O H NH2 (a) What is the molecular formula of this compound? (b) How many sp3 -hybridized carbon atoms are present in this structure? (c) How many sp2 -hybridized carbon atoms are present in this structure? (d) How many sp-hybridized carbon atoms are present in this structure? (e) How many lone pairs are present in this structure? (f) Identify each lone pair as localized or delocalized. (g) Identify the geometry of each atom (except for hydrogen atoms). (h) Draw all significant resonance structures of cycloserine.

Ramelteon is a hypnotic agent used in the treatment of insomnia: Ramelteon O N H O (a) What is the molecular formula of this compound? (b) How many sp3 -hybridized carbon atoms are present in this structure? (c) How many sp2 -hybridized carbon atoms are present in this structure? (d) How many sp-hybridized carbon atoms are present in this structure? (e) How many lone pairs are present in this structure? (f) Identify each lone pair as localized or delocalized. (g) Identify the geometry of each atom (except for hydrogen atoms).

In the compound below, identify all carbon atoms that are electron deficient (d+) and all carbon atoms that are electron rich (d-). Justify your answer with resonance structures. H OH H

Consider the following two compounds: Compound A Compound B O O O O (a) Identify which of these two compounds has greater resonance stabilization. (b) Would you expect compound C (below) to have a resonance stabilization that is more similar to compound A or to compound B? Compound C

Single bonds generally experience free rotation at room temperature (as will be discussed in more detail in Chapter 4): Free rotation of single bond Nevertheless, the single bond shown below exhibits a large barrier to rotation. In other words, the energy of the system is greatly increased if that bond is rotated. Explain the source of this energy barrier. (Hint: Think about the atomic orbitals being used to form the conduit.) ! !

Polymers are very large compounds, assembled from smaller units, called monomers. For example, polymer 2, called poly(vinyl acetate), is made from vinyl acetate (1). Polymer 2 can be converted to polymer 4, called poly(vinyl alcohol), or PVA, via a process called hydrolysis (explored further in Chapter 21). Complete hydrolysis of 2 leads to 4, while incomplete hydrolysis of 2 leads to 3 in which the polymer chain still contains some residual acetate groups. Polymer 2 is one of the main ingredients in white glue, while polymer 3 is present in aqueous PVA glues. Describe how IR spectroscopy can be used to monitor the conversion of 3 to 4. Specifically, describe what you would look for to confirm complete hydrolysis of the acetate groups (J. Chem. Ed. 2006, 83, 15341536). O O O O O O O O 2 OH O OH OH O 3 OH OH OH OH 4

Coumarin and its derivatives exhibit a broad array of industrial applications, including, but not limited to, cosmetics, food preservatives, and fluorescent laser dyes. Some derivatives of coumarin, such as warfarin, exhibit antithrombic activity and are currently used as blood thinners (to prevent the formation of potentially fatal blood clots). Identify how you might use IR spectroscopy to monitor the following reaction, in which compound 1 is converted into a coumarin derivative (compound 2). Describe at least three different signals that you could analyze to confirm the transformation of 1 to 2 (J. Chem. Ed. 2006, 83, 287289). 2 1 N OH H O O O O O O N

CL-20 and HMX are both powerful explosives. CL-20 produces a more powerful blast but is generally considered too shock-sensitive for practical use. HMX is significantly less sensitive and is used as a standard military explosive. When a 2:1 mixture of the two compounds is cocrystallized, the resulting explosive is expected to be more powerful than HMX alone, but with a sensitivity similar to HMX (Cryst. Growth Des. 2012, 12, 43114314). N N N N N N N N NO2 O2N NO2 O2N N N NO2 NO2 NO2 O2N O2N O2N CL-20 HMX (a) What are the molecular formulas for CL-20 and HMX? (b) Consider the lone pair of electrons on one of the nitrogen atoms within the ring(s) for either molecule. Is the lone pair localized or delocalized?

Progesterone is a female hormone that plays a critical role in the menstrual cycle by preparing the lining of the uterus for implantation of an egg. During W. S. Johnsons biomimetic synthesis of progesterone (a synthesis that draws inspiration from and mimics naturally occurring, biosynthetic pathways), one of the final reactions in the synthesis was believed to have proceeded via the following intermediate (J. Am. Chem. Soc. 1971, 93, 43324334). Use resonance structures to explain why this intermediate is particularly stable. ! O H H H O O

Many compounds with desirable medicinal properties are isolated from natural sources and are thus referred to as natural products. However, a compounds medicinal properties are often known before the structure of the compound has been determined. Below are examples of compounds where the first proposed structure was incorrect (Angew. Chem. Int. Ed. 2005, 44, 10121044). In each case, the corresponding correct structure is also shown. Identify all functional groups in each pair of compounds and then compare the similarities and differences between their molecular structures. (a) HO H H H Correct structure of cholesterol OH Proposed structure of cholesterol (b) O NH N OH O OCH3 O O O OCH3 Proposed structure of porritoxin Correct structure of porritoxin

The following compound is an intermediate in the synthesis of a gelator, which is a compound capable of self-assembling to form a gel in an organic liquid (Soft Matter 2012, 8, 54865492). N O H O(CH2)11CH3 O CH3(CH2)11O CH3(CH2)11. (a) Identify each functional group in the molecule. (b) In Chapter 4, we will learn that molecules generally rotate freely around single bonds, while rotation around double bonds is significantly restricted. Consider the four single bonds connecting the two rings in this structure. Two of them can rotate freely, while the other two cannot. Identify the two with restricted rotation and justify your answer by drawing resonance structures

The reaction between an aldehyde and an amine results in the formation of a functional group called an imine, as shown in the following general reaction: + O R R NH2 N R R An imine Consider the reactants AD, which have been used in the synthesis of novel self-assembling molecules with unique and dynamic architectures (Langmuir 2012, 28, 1456714572). ! ! ! ! A D O O O H N (CH2)10 (CH2)10 (CH2)10 (CH2)10 N O O N N H O H2N NH2 C B H2N NH2 (a) Draw the product of the reaction between: i. A and C (2:1 molar ratio) ii. C and D (1:2 molar ratio) iii. A and B (2:1 molar ratio) iv. B and D (1:2 molar ratio) (b) What is the relationship between the products of reactions iii and iv?

The following compound is an amino acid derivative (Chapter 25). In solution, molecules of this compound show a tendency to stick together, or self-assemble, via a series of intermolecular hydrogen bonds. During self-assembly, the growing aggregate can entrap molecules of liquid, thereby forming a gel (J. Am. Chem. Soc. 2009, 131, 1147811484). N N O N O N N O O N H H H H H H (a) Each of the six hydrogen atoms bound directly to nitrogen can form a hydrogen bond, but Hs that are on the amides can form stronger hydrogen bonds than Hs on the amines. Explain why this is so using resonance. (b) Draw the intermolecular hydrogen bonds that form during selfassembly. Do this by drawing three molecules stacked directly on top of each other, each in the orientation shown. Then, draw hydrogen bonds from the central molecule to each of the other two molecules, showing eight intermolecular H bonds between amide Hs on one molecule to amide Os on adjacent molecules.

In Chapter 3, we will explore the factors that render compounds acidic or basic. Tropolone (1) is a compound that is both fairly acidic and fairly basic (J. Org. Chem. 1997, 62, 32003207). It is acidic because it is capable of losing a proton (H+) to form a relatively stable anion (2), while it is basic because of its ability to receive a proton to form cation 3: H+ H+ @ ! O O 1 O O 2 O O 3 H H H (a) Draw all significant resonance structures of anion 2 and of cation 3 and explain why each of these ions is stabilized. (b) In compound 1, the bond lengths for the C!C bonds vary greatly and alternate in length (long, short, long, etc.). But in ions 2 and 3, the lengths of the bonds are similar. Explain. (c) The intramolecular hydrogen bonding interaction in 3 is significantly diminished in comparison to 1. Explain.

Triphenylmethane dyes are among the first synthetic dyes developed for commercial use. A comparison of the structures of these compounds reveals that even small differences in structure can lead to large differences in color (Chem. Rev. 1993, 93, 381433). The structures of three such dyes are shown below. @ N! R R N X Basic violet 4 Basic green 4 Basic red 9 Cl N(C2H5)2 C2H5 X R H CH3 NH2 H R R (a) Draw resonance structures for basic green 4 that illustrate the delocalization of the positive charge. (b) Determine whether basic green 4 or basic violet 4 is expected to have greater resonance stabilization. Justify your choice.

Basic red 1 is a tetracyclic compound (it has four rings) that shares many structural similarities with the dyes in the previous problem (Chem. Rev. 1993, 93, 381433). This compound has many significant resonance structures, and the positive charge is highly delocalized. While resonance structures can be drawn in which the positive charge is spread throughout all four rings, nonetheless, one of the rings likely bears very little of the charge relative to the other rings. Identify the ring that is not participating as effectively in resonance and suggest an explanation. @ ! Cl O N H N H O Basic red 1 O