(a) Outline the syntheses indicated in Solved 18-2, beginning with aldehydes and alkyl

Give the IUPAC name and (if possible) a common name for each compound.

NMR spectra for two compounds are given here, together with the molecular formulas. Each compound is a ketone or an aldehyde. In each case, show what characteristics of the spectrum imply the presence of a ketone or an aldehyde, and propose a structure for the compound.

Why were no products from the McLafferty rearrangement observed in the spectrum of butan-2-one (Figure 18-3)?

Use equations to show the fragmentation leading to each numbered peak in the mass spectrum of octan-2-one.

Oxidation of cholesterol converts the alcohol to a ketone. Under acidic or basic oxidation conditions, the CC double bond migrates to the more stable, conjugated position. Before IR and NMR spectroscopy, chemists watched the UV spectrum of the reaction mixture to follow the oxidation. Describe how the UV spectrum of the conjugated product, cholest-4- en-3-one, differs from that of cholesterol.

Show how you would synthesize each compound from starting materials containing no more than six carbon atoms.

Show how you would accomplish the following synthetic conversions by adding an organolithium reagent to an acid. COOH pentanoic acid heptan-3-one Br (a) (c) (d) phenylacetic acid 3,3-dimethyl-1-phenylbutan-2-one

Predict the products of the following reactions. (a) CH3CH2CH2CH2CN + CH3CH2MgBr, then H3O+ (b) CH3CH2CH2CH2CN + DIBAL-H, then H3O+ (c) benzyl bromide + sodium cyanide (d) product of (c) + cyclopentylmagnesium bromide, then acidic hydrolysis (e) product of (c) + DIBAL-H, then hydrolysis

Show how the following transformations may be accomplished in good yield. You may use any additional reagents that are needed. (a) bromobenzene \(\rightarrow\) propiophenone (b) CH_3CH_2CN \(\rightarrow\) heptan-3-one (c) benzoic acid \(\rightarrow\) phenyl cyclopentyl ketone (d) 1-bromohept-2-ene \(\rightarrow\) oct-3-enal

Predict the products of the following reactions:

Show how you would accomplish the following synthetic conversions. You may use any additional reagents and solvents you need. CHOPh Ph PhC (a) O CPh Ph O OHPh3C (b) CH OH CPh Ph Ph Ph (c) O PhCHO CCH2CH3 PhCHC (d) OH

Sodium triacetoxyborohydride, NaBH(OAc)3, is a mild reducing agent that reduces aldehydes much more quickly than ketones. It can be used to reduce aldehydes in the presence of ketones, such as in the following reaction: CH3 C CH2 O O C H CH3 C CH2 O CH2 OH NaBH(OAc)3 CH3COOH (a) Draw a complete Lewis structure for sodium triacetoxyborohydride. (b) Propose a mechanism for the reduction of an aldehyde by sodium triacetoxyborohydride.

Propose mechanisms for (a) the acid-catalyzed hydration of chloral to form chloral hydrate. (b) the base-catalyzed hydration of acetone to form acetone hydrate.

Rank the following compounds in order of increasing amount of hydrate present at equilibrium.

Propose a mechanism for each cyanohydrin synthesis just shown.

Show how you would accomplish the following syntheses. (a) acetophenone S acetophenone cyanohydrin (b) cyclopentanecarbaldehyde S 2-cyclopentyl-2-hydroxyacetic acid (c) hexan@1@ol S 2-hydroxyheptanoic acid

Propose mechanisms for the three imine-forming reactions just shown.

Depending on the reaction conditions, two different imines of formula C8H9N might be formed by the reaction of benzaldehyde with methylamine. Explain, and give the structures of the two imines.

Give the structures of the carbonyl compound and the amine used to form the following imines.

Propose a mechanism for the hydrolysis of benzaldehyde methyl imine just shown.

2,4-Dinitrophenylhydrazine is frequently used for making derivatives of ketones and aldehydes because the products (2,4-dinitrophenylhydrazones, called 2,4-DNP derivatives) are even more likely than the phenylhydrazones to be solids with sharp melting points. Propose a mechanism for the reaction of acetone with 2,4-dinitrophenylhydrazine in a mildly acidic solution.

Predict the products of the following reactions. O H+ + HONH2 (a) O H+ + H2NNH2 (b) H+ CPh Ph PhNHNH2 O + (c) H+ PhCH CHCHO H2NCNHNH2 O + (d)

Show what amines and carbonyl compounds combine to give the following derivatives. Ph CH O N NH C NH2 (a) NOH (b) (c) N NHPh NO2 NNH O2N (d) N CH3 (e) N N (f)

Propose a mechanism for the acid-catalyzed reaction of benzaldehyde with methanol to give benzaldehyde dimethyl acetal.

Propose a mechanism for the acid-catalyzed hydrolysis of cyclohexanone dimethyl acetal.

Show what alcohols and carbonyl compounds give the following derivatives.

In the mechanism for acetal hydrolysis shown, the ring oxygen atom was protonated first, the ring was cleaved, and then the methoxy group was lost. The mechanism could also be written to show the methoxy oxygen protonating and cleaving first, followed by ring cleavage. Draw this alternative mechanism.

(a) Propose a mechanism for the acid-catalyzed reaction of cyclohexanone with ethylene glycol to give cyclohexanone ethylene acetal. (b) Propose a mechanism for the acid-catalyzed hydrolysis of cyclohexanone ethylene acetal. (c) Compare the mechanisms you drew in parts (a) and (b). How similar are these mechanisms, comparing them in reverse order? (d) Propose a mechanism for the acid-catalyzed hydrolysis of the acetal given in Problem 18-26(f).

Show how you would accomplish the following syntheses. You may use whatever additional reagents you need.

Trimethylphosphine is a stronger nucleophile than triphenylphosphine, but it is rarely used to make ylides. Why is trimethylphosphine unsuitable for making most phosphorus ylides?

Like other strong nucleophiles, triphenylphosphine attacks and opens epoxides. The initial product (a betaine) quickly cyclizes to an oxaphosphetane that collapses to an alkene and triphenylphosphine oxide. (a) Show each step in the reaction of trans-2,3-epoxybutane with triphenylphosphine to give but-2-ene. What is the stereochemistry of the double bond in the product? (b) Show how this sequence might be used to convert cis-cyclooctene to trans-cyclooctene.

(a) Outline the syntheses indicated in Solved Problem 18-2, beginning with aldehydes and alkyl halides. (b) Both of these syntheses of 1-phenylbuta-1,3-diene form the central double bond. Show how you would synthesize this target molecule by forming the terminal double bond.

Show how Wittig reactions might be used to synthesize the following compounds. In each case, start with an alkyl halide and a ketone or an aldehyde. (a) \(Ph - CH = C(CH_3)_2\) (b) \(Ph - C(CH_3) = CH_2\) (c) \(Ph - CH = CH - CH = CH - Ph\)

Predict the major products of the following reactions.

Propose a mechanism for both parts of the Wolff–Kishner reduction of cyclohexanone: the formation of the hydrazone, and then the base-catalyzed reduction with evolution of nitrogen gas.

Predict the major products of the following reactions: O Zn(Hg) HCl, H2O (a) O (1) H2NNH2 (2) KOH, heat (b) O O O (1) N2H4 (2) KOH, heat (c) Zn(Hg) O HCl, H2O

Name ketones and aldehydes, and draw the structures from their names. Identify their hydrates, acetals, imines, and other derivatives. (Problems 18-37, 38, 40, 41, and 61)

Interpret the IR, NMR, UV, and mass spectra of ketones and aldehydes, and use spectral information to determine the structures.

Propose single-step and multistep syntheses of ketones and aldehydes from alcohols, alkenes, alkynes, carboxylic acids, nitriles, acid chlorides, esters, and aromatic compounds. (Problems 18-55, 56, 60, and 64)

Predict the products of reactions of ketones and aldehydes with the following types of compounds, and give mechanisms where appropriate: (a) hydride reducing agents; (b) Clemmensen and Wolff-Kishner reagents; (c) Grignard and organolithium reagents; (d) phosphorus ylides; (e) water; (f) hydrogen cyanide; (g) ammonia and primary amines; (h) hydroxylamine and hydrazine derivatives; (i) alcohols; and (j) oxidizing agents.

Use your knowledge of the mechanisms of ketone and aldehyde reactions to propose mechanisms and products of similar reactions you have never seen before. (Problems 18-50, 58, 62, 63, 68, 69, 70, 72, 73, and 75) Problem-Solving Strategy: Proposing Reaction Mechanisms (Problems 18-50, 58, 62, 63, 68, 69, 70, 72, 73, and 75)

Show how to convert ketones and aldehydes to other functional groups, and devise multistep syntheses using ketones and aldehydes as starting materials and intermediates. (Problems 18-47, 51, 52, 59, and 60)

Draw structures of the following derivatives. (a) the 2,4-dinitrophenylhydrazone of benzaldehyde (b) the semicarbazone of cyclobutanone (c) cyclopropanone oxime (d) the ethylene acetal of hexan-3-one (e) acetaldehyde dimethyl acetal (f) the methyl hemiacetal of formaldehyde (g) the (E) isomer of the ethyl imine of propiophenone (h) the hemiacetal form of 5-hydroxypentanal

Name the following ketones and aldehydes. When possible, give both a common name and an IUPAC name. (a) CH3CO(CH2)4CH3 (b) CH3(CH2)2CO(CH2)2CH3 (c) CH3(CH2)5CHO (d) PhCOPh (e) CH3CH2CH2CHO (f) CH3COCH3 (g) CH3CH2CHBrCH2CH(CH3)CHO (h) PhCHCHCHO (i) CH3CHCHCHCHCHO (j) O O OH (a) (k) CHO (k) O (l) CH3 O CH3

Predict the major products of the following reactions. H+ O PhNHNH2 (a) O OCH3 (b) (2) H2O (1) DIBAL-H (78 C) (c) CN (2) H3O+ (1) DIBAL-H Cl O (d) (CH2CH)2CuLi OCH3 O H3O+ (e) Cl O LiAlH(O-t-Bu)3 (f) COOH (2) H3O+ (1) 2 CH3CH2Li (g) C PPh3 H (h) O + O O H3O+ (i) (lose H2O) H+ CH3 , heat

Rank the following carbonyl compounds in order of increasing equilibrium constant for hydration: CH3COCH2Cl ClCH2CHO CH2O CH3COCH3 CH3CHO

Acetals can serve as protecting groups for 1,2-diols, as well as for aldehydes and ketones. When the acetal is formed from acetone plus the diol, the acetal is called an acetonide. Show the acetonides formed from these diols with acetone under acid catalysis.

Sketch the expected proton NMR spectrum of 3,3-dimethylbutanal.

A compound of formula C6H10O2 shows only two absorptions in the proton NMR: a singlet at 2.67 ppm and a singlet at 2.15 ppm. These absorptions have areas in the ratio 2:3. The IR spectrum shows a strong absorption at 1708 cm-1 . Propose a structure for this compound.

The proton NMR spectrum of a compound of formula \(C_{10}H_{12}O\) follows. This compound reacts with an acidic solution of 2,4-dinitrophenylhydrazine to give a crystalline derivative, but it gives a negative Tollens test. Propose a structure for this compound and give peak assignments to account for the signals in the spectrum.

The following compounds undergo McLafferty rearrangement in the mass spectrometer. Predict the masses of the resulting charged fragments. (a) pentanal (b) 3-methylhexan-2-one (c) 4-methylhexan-2-one

An unknown compound gives a molecular ion of m/z 70 in the mass spectrum. It reacts with semicarbazide hydrochloride to give a crystalline derivative, but it gives a negative Tollens test. The NMR and IR spectra follow. Propose a structure for this compound, and give peak assignments to account for the absorptions in the spectra. Explain why the signal at \(1790 cm^{-1}\) in the IR spectrum appears at an unusual frequency.

Show how you would accomplish the following synthetic conversions efficiently and in good yield. You may use any necessary additional reagents and solvents.

The following road-map problem centers on the structure and properties of A, a key intermediate in these reactions. Give structures for compounds A through J. CH2OH OH PCC (excess) B OH OH (1 equiv) TsOH A Tollens reagent D (1) CH3MgI (2) H3O+ PhNHNH2 (excess) dil H2SO4 C G OH NaBH4 H+ H warm gently I (1) J (2) H3O+ H3O+, then excess NaOCl/HOAc E Zn (Hg) HCl F

For each compound, 1. name the functional group. 2. show what compound(s) result from complete hydrolysis.

Propose mechanisms for the following reactions. O Ph C H Ph C H CH3O OCH3 CH3OH, H+ (a) CH3 C H CH3 C H O PhNHNH N NHPh 2, H+ (b) O CH CH2 2 Ph3P (c) + O O O OH CH2 CH2 OH H+ H2O (d) HN NH3 + CHO H+ H2O (e) OCH3 NCH2CH3 OCH3 + CH3CH2NH3 Cl CH3CH2NH2

Show how you would accomplish the following syntheses efficiently and in good yield. You may use any necessary reagents. (a) acetaldehyde lactic acid, CH3CH(OH)COOH (b) O CHPh CHO O CH2OH (c) O CHO O CHO (d) H OH (e) CHO O CHO CHCH2CH3 (e) (f) O O (g) O OH

Show how you would synthesize the following derivatives from appropriate carbonyl compounds.

Predict the products formed when cyclohexanone reacts with the following reagents. (a) CH3NH2, H+ (b) excess CH3OH, H+ (c) hydroxylamine and weak acid (d) ethylene glycol and p-toluenesulfonic acid (e) phenylhydrazine and weak acid (f) PhMgBr and then mild H3O+ (g) Tollens reagent (h) sodium acetylide, then mild H3O+ (i) hydrazine, then hot, fused KOH (j) Ph3PCH2 (k) sodium cyanide (l) acidic hydrolysis of the product from (k)

Predict the products formed when cyclohexanecarbaldehyde reacts with the following reagents. (a) PhMgBr, then H3O+ (b) Tollens reagent (c) semicarbazide and weak acid (d) excess ethanol and acid (e) propane-1,3-diol, H+ (f) zinc amalgam and dilute hydrochloric acid

Show how you would synthesize octan-2-one from each compound. You may use any necessary reagents. (a) heptanal (b) oct-1-yne (c) 2,3-dimethylnon-2-ene (d) octan-2-ol (e) heptanoic acid (f) CH3(CH2)5CN

Show how you would synthesize octanal from each compound. You may use any necessary reagents. (a) octan-1-ol (b) non-1-ene (c) oct-1-yne (d) 1-bromoheptane (e) 1-bromohexane (f) octanoic acid (g) ethyl octanoate

Both NaBH4 and NaBD4 are commercially available, and D2O is common and inexpensive. Show how you would synthesize the following labeled compounds, starting with butan-2-one.

When \(LiAlH_4\) reduces 3-methylcyclopentanone, the product mixture contains 60% cis-3-methylcyclopentanol and 40% trans-3-methylcyclopentanol. Use your models, and make three-dimensional drawings to explain this preference for the cis isomer.

The Wittig reaction is useful for placing double bonds in less stable positions. For example, the following transformation is easily accomplished using a Wittig reaction. (a) Show how you would use a Wittig reaction to do this. (b) Show how you might do this without using a Wittig reaction, and then explain why the Wittig reaction is a much better synthesis.

Show how you would accomplish the following syntheses. (a) benzene n@butylbenzene (b) benzonitrile propiophenone (c) benzene p@methoxybenzaldehyde (d) Ph (CH2)4 OH

There are three dioxane isomers: 1,2-dioxane, 1,3-dioxane, and 1,4-dioxane. One of these acts like an ether and is an excellent solvent for Grignard reactions. Another one is potentially explosive when heated. The third one quickly hydrolyzes in dilute acid. Show which isomer acts like a simple ether, and then explain why one of them is potentially explosive. Propose a mechanism for the acid hydrolysis of the third isomer.

Two structures for the sugar glucose are shown on page 914. Interconversion of the open-chain and cyclic hemiacetal forms is catalyzed by either acid or base. (a) Propose a mechanism for the cyclization, assuming a trace of acid is present. (b) The cyclic hemiacetal is more stable than the open-chain form, so very little of the open-chain form is present at equilibrium. Will an aqueous solution of glucose reduce Tollens reagent and give a positive Tollens test? Explain.

Two structures of the sugar fructose are shown next. The cyclic structure predominates in aqueous solution. (a) Number the carbon atoms in the cyclic structure. What is the functional group at C2 in the cyclic form? (b) Propose a mechanism for the cyclization, assuming a trace of acid is present.

Hydration of alkynes (via oxymercuration) gives good yields of single compounds only with symmetrical or terminal alkynes. Show what the products would be from hydration of each compound. (a) hex-3-yne (b) hex-2-yne (c) hex-1-yne (d) cyclodecyne (e) 3-methylcyclodecyne

Which of the following compounds would give a positive Tollens test? (Remember that the Tollens test involves mild basic aqueous conditions.) (a) \(CH_3CH_2CH_2COCH_3\) (b) \(CH_3CH_2CH_2CH_2CHO\) (c) \(CH_3CH=CHCH=CHOH\) (d) \(CH_3CH_2CH_2CH_2CH(OH)OCH_3\) (e) \(CH_3CH_2CH_2CH_2CH(OCH_3)_2\)

Solving the following road-map problem depends on determining the structure of A, the key intermediate. Give structures for compounds A through K.

Within each set of structures, indicate which will react fastest, and which slowest, toward nucleophilic addition in basic conditions.

One of these reacts with dilute aqueous acid and the other does not. Give a mechanism for the one that reacts, and show why this mechanism does not work for the other one.

Show a complete mechanism for this equilibrium established in diethyl ether with HCl gas as catalyst.

Show a complete mechanism for this reaction.

The UV spectrum of an unknown compound shows values of lmax at 225 nm (e = 10,000) and at 318 nm (e = 40). The mass spectrum shows a molecular ion at m>z 96 and a prominent base peak at m>z 68. The IR and NMR spectra follow. Propose a structure, and show how your structure corresponds to the observed absorptions. Propose a favorable fragmentation to account for the MS base peak at m>z 68 (loss of C2H4).

(a) Simple aminoacetals hydrolyze quickly and easily in dilute acid. Propose a mechanism for hydrolysis of the following aminoacetal: O H3O+ N

The mass spectrum of unknown compound A shows a molecular ion at m>z 116 and prominent peaks at m>z 87 and m>z 101. Its UV spectrum shows no maximum above 200 nm. The IR and NMR spectra of A follow. When A is washed with dilute aqueous acid, extracted into dichloromethane, and the solvent evaporated, it gives a product B. B shows a strong carbonyl signal at 1715 cm-1 in the IR spectrum and a weak maximum at 274 nm (e = 16) in the UV spectrum. The mass spectrum of B shows a molecular ion of m>z 72. Determine the structures of A and B, and show the fragmentation to account for the peaks at m>z 87 and 101.

(A true story.) The chemistry department custodian was cleaning the organic lab when an unmarked bottle fell off a shelf and smashed on the floor, leaving a puddle of volatile liquid. The custodian began to wipe up the puddle, but he was overcome with burning in his eyes and a feeling of having an electric drill thrust up his nose. He left the room and called the fire department, who used breathing equipment to go in and clean up the chemical. Three students were asked to identify the chemical quickly so that the custodian could be treated and the chemical could be handled properly. The students took IR and NMR spectra, which follow. The UV spectrum showed \(\lambda_{max}\ \text{at}\ 220\ nm\ (\epsilon\ =\ 16,000)\). The mass spectrometer was down, so no molecular weight was available. Determine the structure of this nasty compound, and show how your structure fits the spectra.

In the absence of water, o-phthalaldehyde has the structure shown. Its strongest IR absorption is at 1687 cm-1 ; the proton NMR data are shown by the structure. In the presence of water, a new compound is formed that has a strong IR absorption around 3400 cm-1 and no absorption in the CO region. The proton NMR data are shown. Propose a structure of X consistent with this information, and suggest how X was formed.

Assume you are a research physiologist trying to unravel a serious metabolic disorder. You have fed your lab animal Igor a deuterium-labeled substrate and now need to analyze the urinary metabolites. Show how you would differentiate these four deuterated aldehydes using mass spectrometry. Remember that deuterium has mass 2. (Hint: Predict the important fragmentations, and show how the different compounds give unique peaks.)

The family of macrolide antibiotics all have large rings (macrocycle) in which an ester is what makes the ring; a cyclic ester is termed a lactone. One example is amphotericin B, used as an anti-fungal treatment of last resort because of its liver and heart toxicity. Professor Martin Burke of the University of Illinois has been making analogs to retain the antifungal properties but without the toxicity, including this structure published in 2015. (Nature Chemical Biology (2015) doi:10.1038/nchembio.1821) The carboxylate of amphotericin B has been replaced with the urea group (shown in red). analog of amphotericin B O HO O OH OH O OH OH OH N H N H OH OH O OH OH O O CH3 NH3 + (a) Where is the lactone group that forms the ring? (b) Two groups are circled. What type of functional group are they? Explain.