OCHM – Organic Synthesis Question Information Q-Bank MCAT Sim Non-Sim Subject Organic Chemistry Foundation OCHM – Organic Synthesis Validity 5 years Author(s) Reyes, V. M. Reviewer(s) 0000000 Editor(s) 0000000 Passage Information Passage ID Media ID(s) Passage Stem Synthetic organic chemistry is arguably the most important and most active branch of organic chemistry, and a casual inspection of the chemical literature will attest to that. Synthetic organic chemists are especially in high demand in the drug discovery and manufacturing as well as the big bio-pharma industries. Organic reactions named after their discoverers (“named organic reactions”) alone number a few hundred, and most of them are intended for the synthetic route to novel organic compounds. Synthetic organic reactions involve the formation of new covalent bonds usually involving C-atoms and the reassembly of old ones. The product is usually an organic molecule larger than the reactants involved, and ready for the next synthetic reaction. The ultimate aim is the creation of a new drug or material for specialized purposes (e.g., biomaterials, etc.). In this module, shall focus on the Diels-Alder reaction, an important and time-tested way to create cyclic organic compounds.

The Diels-Alder reaction is a reaction between a conjugated diene (a.k.a., 1,3-diene) and an alkene (a.k.a. olefin ), or sometimes an alkyne (a.k.a. acetylene), to form a 6-membered cyclic adduct containing one or two double bonds in the case of olefins and acetylenes, respectively: R R P T P T heat + pressure Q U Q U S S dienophile (alkene or alkyne) conjugated diene cyclic adduct In the reaction above, P, Q, R, S, T and U are suitable alkyl groups. The alkene or alkyne reactant (red bond in the dienophile in case of alkynes) is often termed the “dienophile” (phile = “loving”; dienophile = “diene-loving”) because of its tendency to react with the conjugated diene. The reaction is carried out under heat and pressure. Since the Diels-Alder reaction produces a cyclic adduct, it is considered as a cyclo-addition reaction of the [4+2] type since it involves 4π electrons of the 1,3-diene and 2π electrons of the olefin (or acetylene). For example, applying heat and pressure to a mixture of 1,3-butadiene and acrolein yields 1,2,5,6-tetrahydrobenzaldehyde: + 10 kbar ∆ 1,3-butadiene acrolein 1,2,5,6-tetrahydrobenzaldehyde 1,3-butadiene plays the role of the conjugated diene, and acrolein the dienophile; the resulting cyclic adduct is 1,2,5,6-tetrahydrobenzaldehyde. Reactivity between diene and dienophile depends on the substituents either molecule has, with electron-donating on the former and electron-withdrawing groups on the latter enhancing adduct formation.

Question Attributes #1 (QID: 000000) Passage References PMID/Page # Title of Publication or Book Type 000000000 R. Brewster & W. McEwen, Organic Chemistry textbook R. W. Griffin, Jr., Modern Organic Chemistry textbook 000000000 (N/A) en.wikipedia.com, youtube.com internet (N/A) Author’s own lecture notes Question Attributes #1 (QID: 000000) Topic Blueprint The Diels-Alder Reaction Competency MCAT: BS-2: Application of Concepts & Principles Objective To gain an understand of the Diels-Alder reaction and be able to predict the product of the reaction given the reactants. Media ID(s) 00000000 Question ID 00000000 Question Stem #1 Cyclopentadiene is known to undergo Diels-Alder adduct formation near room temperature. Predict the molecular structure of the resulting product. 2 ? cyclopentadiene

I. II. IV. III. Answer Choices #1 A) I B) II C) III D) IV Correct: D) III dicyclopentadiene IV. III. (Cont’d. on the next page.)

The correct answer is C, molecule III. Explanation #1 The correct answer is C, molecule III. The first step is to identify the diene and the dienophile. Since in this case they are identical molecules, it is important to identify the conjugated C=C bonds in the diene and the electrophilic C=C or CΞC in the dienophile. They are identified on the right hand side of the above reaction forming incipient bonds. It is thus easy to see that this intermediate will give rise to molecule III. (Choice A) This molecule is cycloheptatriene and is an incorrect choice. It is composed of eight carbon atoms in cyclic, conjugated form. Its formation would have involved the recyclization/reassembly of two molecules of linearized cyclopentadiene which is expected to have 10 carbon atoms, five from each linearized cyclopentadiene, thus this molecule fails to account for two carbon atoms. (Choice B) This choice in incorrect. This molecule is the Diels-Alder adduct product between anthracene and singlet oxygen. This choice may also be eliminated by the fact that the two oxygen atoms in it are unaccounted for. (Choice D) This choice is also incorrect. This compound is azulene, the blue chromophore in chamomile and the blue mushroom. It has 10 π electrons and hence aromatic by Huckel’s rule. The synthetic route to azulene does not involve the Diels- Alder reaction. (Cont’d. on the next page.)

Educational objective: To gain an understand of the Diels-Alder reaction and be able to predict the product of the reaction given the reactants. References #1 PMID/Book Title of Publication or Book 0000000 000000000 000000000 0000000 Verifications #1 Yes / No The question is at the Application or higher cognitive level. Yes / No The question is based on a realistic clinical scenario. Yes / No The question has at least one close distracter, and other options have educational value. Yes / No The question is appropriate to the entry level of nursing practice. Yes / No The explanation is short and concise, yet thorough. Yes / No The question has an appropriate table/flow chart/illustration.