Chapter 1 — Exercises
Thirty-eight exercises. Work them with a pencil — no laptop, no phone — unless a computational exercise says otherwise. The point is to build the habits.
Exercises marked (routine) should take under five minutes each. (moderate) problems require thinking through a definition or piece of reasoning. (challenge) problems go somewhat beyond what Chapter 1 covers and are meant to preview later chapters. Exercises marked with a ∗ have full worked solutions in Appendix Answers to Selected Exercises.
Section A — What counts as organic chemistry
1.1∗ (routine) For each compound, state whether it would conventionally be classified as organic or inorganic:
(a) methanol, $CH_3OH$ (b) sodium chloride, $NaCl$ (c) urea, $(NH_2)_2CO$ (d) carbon dioxide, $CO_2$ (e) benzene, $C_6H_6$ (f) hydrogen cyanide, $HCN$ (g) sodium acetate, $CH_3COONa$ (h) carbon tetrachloride, $CCl_4$
1.2 (moderate) Wöhler's 1828 synthesis of urea from ammonium cyanate is often said to have "disproved vitalism." In one or two sentences, explain what vitalism claimed and why the Wöhler synthesis undermined it.
1.3 (moderate) A student argues that vitalism is equivalent to the modern concept that living systems use enzymes to produce compounds that are difficult to synthesize in a flask without them. Why is this a misreading of the vitalist claim?
1.4 (routine) The Chemical Abstracts Service has registered roughly $2.1 \times 10^8$ compounds. If roughly $3 \times 10^3$ new compounds are added each day, approximately how many years would it take (at constant rate) to double the current number? What does this pace tell you about the discipline?
1.5 (challenge) It is often said that "organic" in "organic chemistry" is a historical artifact. Would you rename the discipline? If so, to what? If not, why not? (One paragraph.)
Section B — Why carbon
1.6∗ (routine) State, without looking, the ground-state electron configuration of a neutral carbon atom. Identify the valence electrons. How many valence electrons does carbon have, and why does this predict a valence of four?
1.7 (routine) For each of the following pairs, which atom forms the stronger single bond to itself? Explain briefly why.
(a) $C-C$ vs $Si-Si$ (b) $C-C$ vs $N-N$ (c) $C=C$ vs $Si=Si$
1.8 (moderate) Silicon and carbon both have four valence electrons and both can form four bonds. Nevertheless, biology uses carbon, not silicon. Give three specific chemical reasons why silicon would not work as a replacement for carbon in biology. (Be more specific than "carbon is better at forming chains.")
1.9 (moderate) Explain, using the concept of electronegativity, why a $C-H$ bond is less polar than an $O-H$ bond. Why does this polarity difference matter for chemistry?
1.10 (routine) Which of the following atoms can form a stable double bond to a carbon atom (for example, in an analogue of a carbonyl group) at room temperature: $N$, $O$, $S$, $Si$, $P$, $F$? Sort the list into "forms stable $C=X$ bonds" and "does not."
1.11∗ (challenge) Carbon forms up to four $\sigma$ bonds to other atoms, and also forms $\pi$ bonds in multiple bonds. Nitrogen can also form three $\sigma$ bonds (plus a lone pair) and can participate in $\pi$ bonds. If nitrogen has a complete octet when it forms three $\sigma$ bonds, why does nitrogen not dominate biology the way carbon does? What does carbon offer that nitrogen does not?
Section C — Structures and drawings
1.12∗ (routine) Using condensed formulas (not skeletal), write the structure of each of the following:
(a) methane (b) ethane (c) propane (d) 2-methylpropane (isobutane) (e) ethanol (f) acetic acid (g) acetone
1.13 (routine) How many distinct constitutional isomers of $C_4H_{10}$ exist? Draw them and name each one.
1.14 (moderate) How many distinct constitutional isomers of $C_5H_{12}$ exist? Draw them.
1.15 (challenge) A chemist in 1800 knew about ethanol, $CH_3CH_2OH$. A student argues that dimethyl ether, $CH_3OCH_3$, should have identical physical properties because it has the same formula ($C_2H_6O$). Why is the student wrong? (Do not use functional-group vocabulary from Chapter 4 — reason only from structure.)
1.16 (moderate) A molecule has molecular formula $C_2H_5Cl$. How many structural isomers are possible? If you count by connectivity alone (ignoring 3D arrangement), what is the answer?
1.17∗ (routine) Count the total number of valence electrons in the following:
(a) $CH_4$ (b) $CH_3Cl$ (c) $NH_3$ (d) $HCN$ (e) $CO$
Section D — Preview of mechanism thinking
1.18∗ (moderate) The reaction of $HCl$ with ethylene ($CH_2=CH_2$) gives chloroethane, $CH_3CH_2Cl$.
(a) Identify which atom of $HCl$ (H or Cl) becomes bonded to which carbon of ethylene. (b) Explain in words which part of $HCl$ is the "electron-poor" part (the electrophile) and which part of ethylene could be considered "electron-rich." (c) This is an addition reaction. Predict what you think the general pattern would be for adding $HBr$ to ethylene. (You have not been taught this yet — reason by analogy.)
1.19 (moderate) Sodium borohydride ($NaBH_4$) reduces aldehydes to primary alcohols. The worked problem in Chapter 1 argued that this could be derived from the mechanism of cyanohydrin formation ($HCN$ + aldehyde → cyanohydrin). Using the same reasoning, predict what $NaBH_4$ would do to a ketone.
1.20 (moderate) Consider two students facing a new organic chemistry problem: - Student A memorizes a list of reactions and looks up the product. - Student B reasons from mechanism.
For each of the following situations, explain which student's approach is more likely to produce the correct answer:
(a) A standard exam question asking for the product of a specific named reaction covered in lecture. (b) An exam question on a substrate the student has never seen before, with a familiar reagent. (c) A research problem where a familiar reagent is used on an unfamiliar substrate.
1.21∗ (challenge) Treatment of methyl bromide ($CH_3Br$) with sodium iodide in acetone gives methyl iodide ($CH_3I$) and a precipitate of sodium bromide ($NaBr$). This is the Finkelstein reaction, which you have not met yet. Reason from first principles:
(a) What kind of reaction has occurred? (Bond broken, bond formed.) (b) What role does sodium iodide play? (c) Why does the reaction proceed rather than reverse? (Hint: think about the solubility of $NaBr$ vs. $NaI$ in acetone.)
Section E — Anchor examples
1.22 (routine) Identify which of the three over-the-counter drugs (aspirin, ibuprofen, acetaminophen) contains:
(a) an ester group (b) an amide group (c) a carboxylic acid (d) a phenol (OH on an aromatic ring) (e) a chiral carbon
1.23∗ (moderate) Thalidomide has molecular formula $C_{13}H_{10}N_2O_4$. Confirm this by counting atoms in Figure 1.2 of the chapter. Then calculate its molecular weight (atomic weights: C 12.01, H 1.01, N 14.01, O 16.00).
1.24 (moderate) The $R$ and $S$ enantiomers of thalidomide have identical $^1H$ NMR spectra when run in an achiral solvent like $CDCl_3$. What does this tell you about NMR as a diagnostic tool for stereochemistry? What does it tell you about the biological activity of a drug?
1.25 (challenge) The thalidomide tragedy led to stricter regulations on drug development. In your own words, write a one-paragraph case for why — given the lessons of thalidomide — pharmaceutical chemists today should develop new drugs as single enantiomers rather than as racemates. List one exception or counterargument.
1.26 (moderate) The $S_{N}2$/$S_{N}1$/$E2$/$E1$ decision framework was previewed in Section 1.6. Which of the five factors (substrate, nucleophile/base, solvent, temperature, leaving group) do you predict will matter most for distinguishing $S_{N}2$ from $S_{N}1$? (Guess based on what you know about the mechanisms — we will confirm in Chapter 13.)
1.27 (challenge) Retrosynthetic analysis starts at the target and works backward. Sketch a (very simple) retrosynthesis of ethanol, $CH_3CH_2OH$. What would you disconnect? What precursors would you propose? (Don't worry about realism — this is a gesture at what the skill looks like.)
Section F — The discipline today
1.28 (routine) Rank the following careers by the amount of organic chemistry they typically involve, from most to least:
(a) medicinal chemist at a pharmaceutical company (b) process chemist at a chemical manufacturing plant (c) forensic chemist in a police laboratory (d) high-school chemistry teacher (e) petroleum geologist (f) materials scientist working on plastics
1.29 (moderate) A pharmaceutical company reports synthesizing 25,000 new compounds in a year to find one drug candidate. What are some reasons the success rate is so low? (Answer from any combination of chemical, biological, and business perspectives.)
1.30 (challenge) Nature synthesizes small organic molecules using enzymes, which are proteins that catalyze specific reactions with extraordinary selectivity. Synthetic chemists use non-enzymatic reagents, which are generally less selective. What are advantages the synthetic chemist has over the enzyme? What are advantages the enzyme has over the synthetic chemist?
Section G — Computational exercises
1.31 (computational) Install Avogadro (see Appendix E). Build a propane molecule ($CH_3CH_2CH_3$). Rotate it. Observe: how many hydrogens are on each carbon? How do you distinguish the $CH_3$ carbons from the $CH_2$ carbon in the 3D model?
1.32 (computational) In Avogadro, build cyclohexane ($C_6H_{12}$) and optimize its geometry. Rotate to observe the chair shape. How do the six carbons arrange themselves? Then build benzene ($C_6H_6$) — six carbons with alternating double bonds. Optimize. Compare the two shapes.
1.33 (computational) Build methanol ($CH_3OH$) and ethanol ($CH_3CH_2OH$) in Avogadro. Display the dipole moment (Extensions → Dipole). Which has a larger dipole? What does this suggest about their relative interactions with water?
Section H — Integrative problems
1.34∗ (challenge) A student observes that aspirin is stable as a solid at room temperature for years, but hydrolyzes slowly in the presence of moisture to give salicylic acid and acetic acid. Using only concepts from Chapter 1:
(a) Identify the bond in aspirin that breaks in hydrolysis. (b) Predict which atom of aspirin the water attacks. (c) This is a mechanism problem (nucleophilic acyl substitution, Chapter 26). Sketch, in words, what you think happens electronically. You do not have to be correct — this is a preview.
1.35 (challenge) The price of aspirin has dropped roughly 99% in real terms from 1900 to today, while the yield of the typical aspirin synthesis has stayed roughly constant at about 80%. What factors, other than the reaction yield, have driven the cost reduction? (Think about scale, solvent recycling, catalyst development, purification methods, quality control.)
1.36 (challenge) Read the following primary-source abstract:
"A new class of small-molecule anti-cancer agents, called proteolysis-targeting chimeras (PROTACs), uses thalidomide as a binding scaffold to direct the cellular ubiquitin-proteasome system to degrade specific disease-causing proteins..."
What, in two or three sentences, is the molecular logic of a PROTAC? Why is thalidomide a useful starting point? What does this tell you about the relationship between a molecule's history and its utility?
1.37 (challenge) Estimate: if an organic chemistry research group synthesizes 50 new compounds per week, and each compound requires roughly 20 mL of solvent to synthesize and 100 mL to purify, how much solvent waste does the group generate per year? Convert your answer to liters and tonnes. What does this suggest about the motivation for green chemistry (Chapter 40)?
1.38 (challenge) Choose any one drug in your household's medicine cabinet. Look up its structure on DrugBank (https://go.drugbank.com/). Identify how many carbons, how many oxygens, how many nitrogens it contains. Does it have any stereocenters? How many rings? What functional groups can you recognize (ester, amide, phenol, carboxylic acid, amine, etc., with help from the next few chapters)? Write a one-paragraph note about what you found.
Reading ahead
- Chapter 2 opens by asking what does a carbon atom look like at the electronic level? Preview questions: what is an orbital? What is hybridization? What is the difference between a $\sigma$ and a $\pi$ bond?
- Chapter 3 introduces $pK_a$ as the master framework for predicting acidity, nucleophilicity, leaving-group ability, and equilibrium position. Have an electronic or printed $pK_a$ table (Appendix B) ready when you start Chapter 3.