Organic Chemistry 2nd Edition solutions

Organic Chemistry 2
Spermine is a naturally occurring compound that contributes to the characteristic odor of semen. Classify each nitrogen atom in spermine as primary, secondary, or tertiary. H2N N H N H NH2 Spermine

Organic Chemistry 2
Clomipramine is marketed under the trade name Anafranil and is used in the treatment of obsessive compulsive disorder. Clomipramine N Cl N (a) Identify which nitrogen atom in clomipramine is more basic and justify your choice. (b) Draw the form of clomipramine that is expected to predominate at physi

Organic Chemistry 2
Cinchocaine is a long-acting local anesthetic used in spinal anesthesia. Identify the most basic nitrogen atom in cinchocaine. Cinchocaine N O O N H N

Organic Chemistry 2
For each pair of compounds, identify the stronger base. N N vs. (a) N N O (b) vs. HN H N HN NH (c) vs

Organic Chemistry 2
Draw the structure of each of the following compounds: (a) N-Ethyl-N-isopropylaniline (b) N,N- Dimethylcyclopropylamine (c) (2R,3S)-3-(N,N-Dimethylamino)-2-pentanamine (d) Benzylamine

Organic Chemistry 2
Consider the structure of lysergic acid diethylamide (LSD), a potent hallucinogen containing three nitrogen atoms. One of these three nitrogen atoms is significantly more basic than the other two. Identify the most basic nitrogen atom in LSD and explain your choice. LSD N H N O N H

Organic Chemistry 2
Identify the number of chirality centers in each of the following structures: NH2 (a) N (b) (c) N

Organic Chemistry 2
Assign a name for each of the following compounds: NH2 (a) O NH2 (b) N (c) NH2 (d) Br N (e) N (f)

Organic Chemistry 2
Draw all constitutional isomers with molecular formula C4H11N and provide a name for each isomer.

Organic Chemistry 2
Draw all tertiary amines with molecular formula C5H13N and provide a name for each isomer. Are any of these compounds chiral?

Organic Chemistry 2
Each pair of compounds below will undergo an acid-base reaction. In each case, identify the acid, identify the base, draw curved arrows that show the transfer of a proton, and draw the products. N OH O (a) + N OH O (b) +

Organic Chemistry 2
Draw the structure of the major product obtained when aniline is treated with each of the following reagents: (a) Excess Br2 (b) PhCH2COCl, py (c) Excess methyl iodide (d) NaNO2 and HCl followed by H3PO2 (e) NaNO2 and HCl followed by CuCN

Organic Chemistry 2
Identify how you would make each of the following compounds from 1-hexanol: (a) Hexylamine (b) Heptylamine (c) Pentylamine

Organic Chemistry 2
Identify how you would make hexylamine from each of the following compounds: (a) 1-Bromohexane (b) 1-Bromopentane (c) Hexanoic acid (d) 1-Cyanopentane

Organic Chemistry 2
Tertiary amines with three different alkyl groups are chiral but cannot be resolved because pyramidal inversion causes racemization at room temperature. Nevertheless, chiral aziridines can be resolved and stored at room temperature. Aziridine is a three-membered heterocycle containing a nitrogen atom

Organic Chemistry 2
Lidocaine is one of the most widely used local anesthetics. Draw the form of lidocaine that is expected to predominate at physiological pH. Lidocaine N O H N

Organic Chemistry 2
Propose a mechanism for the following transformation: H H O NH3 CH3NH2 [H+] NaBH3CN

Organic Chemistry 2
When aniline is treated with fuming sulfuric acid, an electrophilic aromatic substitution reaction takes place at the meta position instead of the para position, despite the fact that the amino group is an ortho-para director. Explain this curious result. NH2 NH2 SO3H Fuming H2SO4

Organic Chemistry 2
para-Nitroaniline is an order of magnitude less basic than metanitroaniline. (a) Explain the observed difference in basicity. (b) Would you expect the basicity of ortho-nitroaniline to be closer in value to meta-nitroaniline or to para-nitroaniline?

Organic Chemistry 2
Methadone is a powerful analgesic that is used to suppress withdrawal symptoms in the rehabilitation of heroin addicts. Identify the major product that is obtained when methadone is subjected to a Hofmann elimination. Methadone O N

Organic Chemistry 2
In general, nitrogen atoms are more basic than oxygen atoms. However, when an amide is treated with a strong acid, such as sulfuric acid, it is the oxygen atom of the amide that is protonated, rather than the nitrogen atom. Explain this observation.

Organic Chemistry 2
Propose a synthesis for each of the following transformations: N O (a) COOH (b)

Organic Chemistry 2
Draw a mechanism for the last step of the Gabriel synthesis, performed under basic conditions. N O O R RNH2 COO COO NaOH @ @ +

Organic Chemistry 2
One variation of the Gabriel synthesis employs hydrazine to free the amine in the final step of the synthesis. Draw the by-product obtained in this process. N O O R RNH2 H2N NH2 + ?

Organic Chemistry 2
Predict the major product for each of the following reactions: N H 1) Excess MeI 2) Ag2O, H2O, heat (a) ? N O O H 1) KOH 2) EtBr 3) H2NNH2 (b) ? Br 1) NaCN, DMSO 3) SOCl2 4) excess NH3 2) H3O+, heat (c) ? 1) HNO3, H2SO4 2) Fe, H3O+ 3) NaNO2, HCl (d) 4) CuCN ?

Organic Chemistry 2
Fill in the missing reagents: O N CHO CHO NH2 NH2 a b c d

Organic Chemistry 2
In this chapter, we explained why pyrrole is such a weak base, but we did not discuss the acidity of pyrrole. In fact, pyrrole is 20 orders of magnitude more acidic than most simple amines. Draw the conjugate base of pyrrole and explain its relatively high acidity.

Organic Chemistry 2
Rimantadine is an antiviral drug used to treat people infected with life-threatening influenza viruses. Identify the starting ketone that would be necessary in order to prepare rimantadine via a reductive amination. Rimantadine NH2

Organic Chemistry 2
Benzphetamine is an appetite suppressant that is marketed under the trade name Didrex and used in the treatment of obesity. Identify at least two different ways to make benzphetamine via a reductive amination process. Benzphetamine N

Organic Chemistry 2
Draw the product formed when each of the following compounds is treated with NaNO2 and HCl: NH2 (a) H N (b)

Organic Chemistry 2
Consider the structure of the azo dye called alizarine yellow R (below). Show the reagents you would use to prepare this compound via an azo coupling process. N N OH OH O O2N

Organic Chemistry 2
Draw the major product(s) that are expected when each of the following amines is treated with excess methyl iodide and then heated in the presence of aqueous silver oxide. NH2 (a) NH2 (b)

Organic Chemistry 2
Predict the major product(s) for each of the following reactions: NO2 Br 1) Fe, H3O+ 2) NaOH (a) ? NH2 O [H+] (b) + NaBH3CN ? CN 1) xs LAH 2) H2O (c) ? N O 1) xs LAH 2) H2O (d) ?

Organic Chemistry 2
meta-Bromoaniline was treated with NaNO2 and HCl to yield a diazonium salt. Draw the product obtained when that diazonium salt is treated with each of the following reagents: (a) H2O (b) HBF4 (c) CuCN (d) H3PO2 (e) CuBr

Organic Chemistry 2
Draw the expected product of the following reductive amination: O NH2 [H2SO4] NaBH3CN ?

Organic Chemistry 2
Starting with benzene and any reagents with three or fewer carbon atoms, show how you would prepare each of the following compounds: N H (a) Cl Cl Cl O NH2 (b) N H O (c) N N NH2 (d)

Organic Chemistry 2
Draw the structures of all isomeric amines with molecular formula C6H15N that are not expected to produce any signal above 3000 cm-1 in their IR spectra.

Organic Chemistry 2
When the following compound is treated with excess methyl iodide, a quaternary ammonium salt is obtained that bears only one positive charge. Draw the structure of the quaternary ammonium salt. O N H NH2

Organic Chemistry 2
Draw a mechanism for the following transformation: N H O N H N Cl O N H Cl@ ! + +

Organic Chemistry 2
A compound with molecular formula C5H13N exhibits three signals in its proton NMR spectrum and no signals above 3000 cm-1 in its IR spectrum. Draw two possible structures for this compound.

Organic Chemistry 2
Coniine has molecular formula C8H17N and was present in the hemlock extract used to execute the Greek philosopher Socrates. Subjecting coniine to a Hofmann elimination produces (S)- N,Ndimethyloct-7-en-4-amine. Coniine exhibits one peak above 3000 cm-1 in its IR spectrum. Draw the structure of coniin

Organic Chemistry 2
Piperazine is an antihelminthic agent (a drug used in the treatment of intestinal worms) that has molecular formula C4H10N2. The proton NMR spectrum of piperazine exhibits two signals. When dissolved in D2O, one of these signals vanishes over time. Propose a structure for piperazine.

Organic Chemistry 2
Primary or secondary amines will attack epoxides in a ringopening process: RNH2 OH NR H O For substituted epoxides, nucleophilic attack generally takes place at the less sterically hindered side of the epoxide. Using this type of reaction, show how you might prepare the following compound from benzen

Organic Chemistry 2
Phenacetin was widely used as an analgesic before it was removed from the market in 1983 on suspicion of being a carcinogen. It was widely replaced with acetaminophen (Tylenol), which is very similar in structure but is not carcinogenic. Starting with benzene and using any other reagents of your choi

Organic Chemistry 2
Propose a mechanism for the following process: O N2 CO2 O Heat N O O N @ ! + +

Organic Chemistry 2
Draw the structure of the compound with molecular formula C6H15N that exhibits the following 1 H NMR and 13C NMR spectra: Proton NMR Carbon NMR 2 3 45.8 Chemical Shift (ppm) Chemical Shift (ppm) 3.0 2.8 2.6 2.22.4 2.0 1.8 1.6 1.4 1.2 1.0 0.8 0.6 0.4 70 60 50 40 30 20 10 0 11.3

Organic Chemistry 2
Draw the structure of the compound with molecular formula C8H11N that exhibits the following 1 H NMR and 13C NMR spectra: Proton NMR Carbon NMR 5 138.8 128.4 126.1 43.5 40.0 128.8 2 2 2 Chemical Shift (ppm) Chemical Shift (ppm) 7 140 130 120 110 100 90 80 70 60 50 40 6 5 4 3 2 1

Organic Chemistry 2
Using benzene as your only source of carbon atoms and ammonia as your only source of nitrogen atoms, propose an efficient synthesis for the following compound:

Organic Chemistry 2
Propose an efficient synthesis for the following transformation: N

Organic Chemistry 2
When 3-methyl-3-phenyl-1-butanamine is treated with sodium nitrite and HCl, a mixture of products is obtained. The following compound was found to be present in the reaction mixture. Account for its formation with a complete mechanism (make sure to show the mechanism of formation for a nitrosonium io

Organic Chemistry 2
Guanidine lacks a negative charge but is an extremely powerful base. In fact, it is almost as strong a base as a hydroxide ion. Identify which nitrogen atom in guanidine is so basic and explain why guanidine is a much stronger base than most other amines. H2N NH2 NH Guanidine

Organic Chemistry 2
In the first asymmetric synthesis of (-)-(S,S)-homaline, a symmetrical alkaloid isolated in the early 1970s, a key intermediate was compound 2 (Tetradhedron Lett. 2012, 53, 11191121). Provide reagents for converting compound 1 into compound 2. Ph CO2Me HN Cl Ph CO2Me N N3 Me Two steps 1 2

Organic Chemistry 2
Nicotine is well known for its addictive characteristic in cigarettes. Interestingly, it has also been suggested to have potential therapeutic potential in central nervous system disorders such as Alzheimers disease, Parkinsons disease, and depression. However, due to the toxic side effects of nicoti

Organic Chemistry 2
Halosaline is a naturally occurring alkaloid isolated from the herb Lobelia inflata. Its synthesis was recently completed by an azide reduction followed by an amide reduction (Org. Lett. 2007, 9, 2673 2676). The first of these steps was a ring contraction that converted a lactone to a lactam, shown h

Organic Chemistry 2
The formal synthesis of quinine in 1944 by Woodward and Doering was a landmark achievement (J. Am. Chem. Soc. 1945, 67, 860874). During their synthesis, the following compound was treated with excess methyl iodide, followed by a strong alkali solution of NaOH. Under these conditions, the initial Hofm

Organic Chemistry 2
Piperazinone derivatives, such as compound 4, are being investigated for their potential use in the treatment of migraines as well as a variety of other diseases, including hypertension and sepsis. The following two-step synthetic procedure was developed as a general method for producing a variety of

Organic Chemistry 2
Alkylating agents are compounds capable of transferring an alkyl group to a suitable nucleophile, and they represent an important class of anticancer agents. These agents can transfer an alkyl group to DNA (in a cancer cell), causing structural changes that ultimately lead to cell death. The product

Organic Chemistry 2
Enaminoesters (also called vinylogous carbamates), such as compound 4 below, can serve as building blocks in the synthesis of nitrogen heterocycles. Compound 4 was prepared from compound 1 in a one-pot method (the entire transformation took place in one reaction vessel). Compound 1 was first converte

Organic Chemistry 2
The following reaction was attempted during the total synthesis of crispine A, a cytotoxic alkaloid isolated from a Mongolian thistle (J. Org. Chem. 2011, 76, 16051613). Propose a plausible mechanism for the formation of compound 2 from amine 1. H3CO H3CO NH2 CO2CH3 O Cl [H3O+] H3CO H3CO N CO2CH3 1 2

Organic Chemistry 2
During a recent study of epibatidine, a powerful analgesic isolated from an Ecuadorian poison dart frog, the investigators employed an interesting fragmentation reaction to access ring-opened analogues (J. Org. Chem. 1999, 64, 49664968). Propose a plausible mechanism for the following transformation:

Organic Chemistry 2
Propose a plausible mechanism for the following transformation and justify the stereochemical outcome (J. Org. Chem. 1999, 64, 46174626): O N R CO2Me CO2Me Heat MeOH N R OH MeO