Shown below is a synthesis of the elm bark beetle pheromone, multistriatin (see 16.44)

For all practical purposes, the compound cyclohexa-2,4-dien-1-one exists totally in its Practice Problem 18.1 enol form. Write the structure of cyclohexa-2,4-dien-1-one and of its enol form. What special factor accounts for the stability of the enol form?

Would optically active ketones such as the following undergo acid- or base-catalyzed racemization? Explain your answer.

Write a mechanism using sodium ethoxide in ethanol for the epimerization of cis-decalone Practice Problem 18.3 to trans-decalone. Draw chair conformational structures that show why trans-decalone is more stable than cis-decalone. You may find it helpful to also examine handheld molecular models of cis- and trans-decalone.

Why do we say that the halogenation of ketones in a base is base promoted rather than base catalyzed?

Additional evidence for the halogenation mechanisms that we just presented comes from the following facts: (a) Optically active 2-methyl-1-phenylbutan-1-one undergoes acid-catalyzed racemization at a rate exactly equivalent to the rate at which it undergoes acid-catalyzed halogenation. (b) 2-Methyl-1-phenylbutan-1-one undergoes acid-catalyzed iodination at the same rate that it undergoes acid-catalyzed bromination. (c) 2-Methyl-1- phenylbutan-1-one undergoes base-catalyzed hydrogendeuterium exchange at the same rate that it undergoes base-promoted halogenation. Explain how each of these observations supports the mechanisms that we have presented.

(a) Write a reaction involving a lithium enolate for introduction of the methyl group in the following compound (an intermediate in a synthesis by E. J. Corey of cafestol, an anti-inflammatory agent found in coffee beans): O O (b) Dienolates can be formed from b-keto esters using two equivalents of LDA. The dienolate can then be alkylated selectively at the more basic of the two enolate carbons. Write a reaction for synthesis of the following compound using a dienolate and the appropriate alkyl halide:

Show how you would use the acetoacetic ester synthesis to prepare (a) 3-propyl-2- hexanone and (b) 4-phenyl-2-butanone.

The acetoacetic ester synthesis generally gives best yields when primary halides are used in the alkylation step. Secondary halides give low yields, and tertiary halides give practically no alkylation product at all. (a) Explain. (b) What products would you expect from the reaction of sodioacetoacetic ester and tert-butyl bromide? (c) Bromobenzene cannot be used as an arylating agent in an acetoacetic ester synthesis in the manner we have just described. Why not?

In the synthesis of the keto acid just given, the dicarboxylic acid decarboxylates in a Practice Problem 18.9 specific way; it gives rather than O OH O O OH O Explain.

How would you use the acetoacetic ester synthesis to prepare the following?

Outline all steps in a malonic ester synthesis of each of the following: (a) pentanoic acid, (b) 2-methylpentanoic acid, and (c) 4-methylpentanoic acid.

The antiepileptic drug valproic acid is 2-propylpentanoic acid (administered as the sodium salt). One commercial synthesis of valproic acid begins with ethyl cyanoacetate. The penultimate step of this synthesis involves a decarboxylation, and the last step involves hydrolysis of a nitrile. Outline this synthesis.

Show how you could employ enamines in syntheses of the following compounds:

Rank the following in order of increasing acidity for the indicated hydrogen atoms (bold) (1 = least acidic; 4 = most acidic).

Treating a solution of cis-1-decalone with base causes an isomerization to take place. When the system reaches equilibrium, the solution is found to contain about 95% trans-1-decalone and about 5% cis-1-decalone. Explain this isomerization

Explain the variation in enol content that is observed for solutions of acetylacetone (pentane-2,4-dione) in the several solvents indicated:

Provide a structural formula for the product from each of the following reactions.

Write a stepwise mechanism for each of the following reactions.

Outline syntheses of each of the following from acetoacetic ester and any other required reagents: (a) tert-Butyl methyl ketone (c) 2,5-Hexanedione (e) 2-Ethyl-1,3-butanediol (b) 2-Hexanone (d) 4-Hydroxypentanoic acid (f) 1-Phenyl-1,3-butanediol

Outline syntheses of each of the following from diethyl malonate and any other required reagents: (a) 2-Methylbutanoic acid (b) 4-Methyl-1-pentanol

Provide a structural formula for the product from each of the following reactions

The synthesis of cyclobutanecarboxylic acid given in Section 18.7 was first carried out by William Perkin, Jr., in 1883, and it represented one of the first syntheses of an organic compound with a ring smaller than six carbon atoms. (There was a general feeling at the time that such compounds would be too unstable to exist.) Earlier in 1883, Perkin reported what he mistakenly believed to be a cyclobutane derivative obtained from the reaction of acetoacetic ester and 1,3-dibromopropane. The reaction that Perkin had expected to take place was the following: O OEt O Br Br O OEt O EtONa The molecular formula for his product agreed with the formulation given in the preceding reaction, and alkaline hydrolysis and acidification gave a nicely crystalline acid (also having the expected molecular formula). The acid, however, was quite stable to heat and resisted decarboxylation. Perkin later found that both the ester and the acid contained six-membered rings (five carbon atoms and one oxygen atom). Recall the charge distribution in the enolate ion obtained from acetoacetic ester and propose structures for Perkins ester and acid.

a) In 1884 Perkin achieved a successful synthesis of cyclopropanecarboxylic acid from sodiomalonic ester and 1,2-dibromoethane. Outline the reactions involved in this synthesis. (b) In 1885 Perkin synthesized five-membered carbocyclic compounds D and E in the following way: EtO O OEt O Br Br B 999999999: (1) HO/H2O (2) H3O Na C 99:heat D E 9: A (C17H28O8) (C9H10O8) (C7H10O4) (C7H10O4 (C ) 17H28O8) 99999: 2 EtONa 9: Br2 where D and E are diastereomers; D can be resolved into enantiomeric forms while E cannot. What are the structures of AE? (c) Ten years later Perkin was able to synthesize 1,4-dibromobutane; he later used this compound and diethyl malonate to prepare cyclopentanecarboxylic acid. Show the reactions involved.

Synthesize each of the following compounds from diethyl malonate or ethyl acetoacetate and any other organic and inorganic reagents.

Outline a reaction sequence for synthesis of each of the following compounds from the indicated starting material and any other organic or inorganic reagents needed.

Linalool, a fragrant compound that can be isolated from a variety of plants, is 3,7-dimethyl-1,6-octadien-3-ol. Linalool is used in making perfumes, and it can be synthesized in the following way: sodioacetoacetic ester F (C5H9Br) HBr G (C11H18O3) H (C8H14O) I (C10H16O) linalool (1) dil. NaOH (2) H3O (3) heat (1) LiC#CH (2) H3O H2 Lindlars catalyst Outline the reactions involved. (Hint: Compound F is the more stable isomer capable of being produced in the first step.)

Compound J, a compound with two four-membered rings, has been synthesized by the following route. Outline the steps that are involved. C13H20O4 C9H12O4 J (C8H12O2) CO2 heat 999999999: (1) HO, H2O (2) H3O C10H16O4 C6H12O2 C6H10Br 99: 2 (1) LiAlH4 HBr (2) H2O 2 NaOEt EtO O OEt O 9: C10H17BrO4 99999: NaOEt EtO O OEt O

ldehydes that have no a hydrogen undergo an intermolecular oxidationreduction called the Cannizzaro reaction when they are treated with concentrated base. An example is the following reaction of benzaldehyde: H O OH O O 2 99: HO H2O (a) When the reaction is carried out in D2O, the benzyl alcohol that is isolated contains no deuterium bound to carbon. It is C6H5CH2OD. What does this suggest about the mechanism for the reaction? (b) When (CH3)2CHCHO and Ba(OH)2/H2O are heated in a sealed tube, the reaction produces only (CH3)2CHCH2OH and [(CH3)2CHCO2]2Ba. Provide an explanation for the formation of these products.

Shown below is a synthesis of the elm bark beetle pheromone, multistriatin (see Problem 16.44). Give structures for compounds A, B, C, and D.

(a) A compound U (C9H10O) gives a negative iodoform test. The IR spectrum of U shows a strong absorption peak at 1690 cm-1 . The 1 H NMR spectrum of U gives the following: Triplet d 1.2 (3H) Quartet d 3.0 (2H) Multiplet d 7.7 (5H) What is the structure of U? (b) A compound V is an isomer of U. Compound V gives a positive iodoform test; its IR spectrum shows a strong peak at 1705 cm-1 . The 1 H NMR spectrum of V gives the following: Singlet d 2.0 (3H) Singlet d 3.5 (2H) Multiplet d 7.1 (5H) What is the structure of V?

Compound A has the molecular formula C6H12O3 and shows a strong IR absorption peak at 1710 cm-1 . When treated with iodine in aqueous sodium hydroxide, A gives a yellow precipitate. When A is treated with Tollens reagent (a test for an aldehyde or a group that can be hydrolyzed to an aldehyde), no reaction occurs; however, if A is treated first with water containing a drop of sulfuric acid and then with Tollens reagent, a silver mirror (positive Tollens test) forms in the test tube. Compound A shows the following 1 H NMR spectrum: Singlet d 2.1 Doublet d 2.6 Singlet d 3.2 (6H) Triplet d 4.7 Write a structure for A

The following is an example of a reaction sequence developed by Derin C. DAmico and Michael E. Jung (UCLA) that results in enantiospecific formation of two new chirality centers and a carboncarbon bond. The sequence includes a HornerWadsworthEmmons reaction (Section 16.10B), a Sharpless asymmetric epoxidation (Section 11.13), and a novel rearrangement that ultimately leads to the product. Propose a mechanism for rearrangement of the epoxy alcohol under the conditions shown to form the aldol product. [Hint: The rearrangement can also be accomplished by preparing a trialkylsilyl ether from the epoxy alcohol in a separate reaction first and then treating the resulting silyl ether with a Lewis acid catalyst (e.g., BF3).]

b-Carotene is a highly conjugated hydrocarbon with an orange-red color. Its biosynthesis occurs via the isoprene pathway (Special Topic E in WileyPLUS), and it is found in, among other sources, pumpkins. One of the chemical syntheses of b-carotene was accomplished near the turn of the twentieth century by W. Ipatiew (Ber. 1901, 34, 594596). The first few steps of this synthesis involve chemistry that should be familiar to you. Write mechanisms for all of the reactions from compounds 2 to 5, and from 8 to 9 and 10.

Dehydroabietic acid is a natural product isolated from Pinus palustris. It is structurally related to abietic acid, which comes from rosin. The synthesis of dehydroabietic acid (J. Am. Chem. Soc. 1962, 84, 284292) was accomplished by Gilbert Stork. In the course of this synthesis, Stork discovered his famous enamine reaction. (a) Write detailed mechanisms for the reactions from 5 to 7 below. (b) Write detailed mechanisms for all of the reactions from 8 to 9a in Storks synthesis of dehydroabietic acid. Note that 9a contains a dithioacetal, which forms similarly to acetals you have already studied (Chapter 16).