All information and images from my personal notes and the Organic Chemistry with Biological Concepts Textbook by Janice Gorzynski Smith Heidi R. Vollmer-Snarr Chapter 16 – Conjugation, Resonance, and Dienes

• Conjugation occurs whenever p orbitals can overlap on three of more adjacent atoms

• 1,3-Dienes = contain two carbon-carbon double bonds joined by a single sigma

bond o The four p orbitals on adjacent atoms make a 1,3-diene a conjugated

system

• When p orbitals overlap, the electron density in each of the pi bonds is spread out over a larger volume, thus lowering the energy of the molecule and making it more stable

• Two resonance structures differ in the placement of pi bonds and nonbonded electrons. The placement of atoms and sigma bonds stays the same

• Draw two more resonance structures for the following:

• In a system X=Y-Z:, Z is generally sp2 hybridized, and the nonbonded electron

pair occupies a p orbital to make the system conjugated

• S-cis conformation = two double bonds on the same side of the single bond

• S-trans conformation = two double bonds on opposite sides of the single bond

• Four features distinguish conjugated dienes from isolated dienes o The C-C single bond joining the two double bonds is unusually short o Conjugated dienes are most stable that similar isolated dienes o Some reactions of conjugated dienes are different than reactions of

isolated double bonds o Conjugated dienes absorb longer wavelengths of ultraviolet light

• Use resonance theory to explain why the labeled C-O bond lengths are equal:

• Heat of hydrogenation = the more stable diene has the smaller heat of

hydrogenation

• Electrophilic addition in conjugated dienes gives a mixture of products – the 1,2 kinetic product (major product at low temperature), and the 1,4 thermodynamic product (major product at high temperature)

o Form two products because of the resonance-stabilized allylic carbocation

intermediate o The more substituted alkene is the thermodynamic product

• Diels-Alder Reaction

• All Diels-Alder reactions have the following features in common:

o Initiated by heat (thermal reaction) o Form six-membered rings o Three pi bonds break, and two new C-C sigma bonds and one new C-C pi

bond form o They are concerted (all bonds are broken and formed in a single step)

• Rules governing the Diels-Alder Reaction o The diene can react only when it adopts the s-cis conformation o Electron-withdrawing substituents in the dienophile increase the reaction

rate o The stereochemistry of the dienophile is retained in the product o When endo and exo products are possible, the endo product is preferred

Endo = substituent is closer to the longer bridge that joins the two carbons common to both ring

Exo = substituent closer to the shorter bridge that joins the carbons together

• Conjugated dienes and polyenes absorb lights in the UV region of the

electromagnetic spectrum (200-400 nm) Chapter 16 Quick Review

1. Which of the following structure contains conjugated double bond?

2. What is the hybridization around the indicated oxygen atom in the following

anion?

3. Rank the following anions from most to least stable, listing the most stable first.

4. What is (are) the major products of the following reaction?

5. What is the major organic product of the following reaction?

Chapter 17

• Aromatic compound o Cyclic, planar, completely conjugated, that contains 4n+2 pi electrons o More stable than a similar acyclic compound having the same number of

pi electrons

• Antiaromatic compound o Cyclic, planar, completely conjugated, that contain 4n pi electrons o Less stable than a similar acyclic compound having the same number of pi

electrons

• Nonaromatic compound o A compound that lacks one (or more) of the four requirements to be

aromatic and antiaromatic

• Properties of aromatic compounds o Every atom in an aromatic ring has a p orbital to delocalize electron

density o Aromatic compounds are unusually stable, having a smaller heat of

hydrogenation o Have highly deshielded protons on the H NMR spectrum o All bonding Mos and HOMOs are completely filled and no electron occupy

antibonding orbitals’

• Ortho, Para, Meta

• When a heteroatom is already part of a double bond (as in the N of pyridine), its

lone pair cannot occupy a p orbital and so it cannot be delocalized over the ring

• When a heteroatom is not part of a double bond (as in the N of pyrrole), its lone pair can be located in a p orbital and delocalized over a ring to make it aromatic

Chapter 17/18 Quick Review

1. What is the major organic product obtained from the following reaction?

2. What is the major organic product obtained from the following reaction?

3. Rank the following compounds in order of increasing reactivity in electrophilic

aromatic substitution?

4. What is (are) the product(s) of the following reaction?

5. Rank the following compounds in order of decreasing reactivity in electrophilic

aromatic substitution.

Chapter 18

• Electrophilic Aromatic Substitution = replace of H on the benzene ring with another substituent

o Follows a two-step mechanism, reaction of the aromatic ring with an electrophile forms a carbocation, and loss of a proton regenerates the aromatic ring

First step = rate-determining (slow) o The intermediate carbocation is stabilized by resonance

• All ortho, para directors except the halogens activate the benzene ring

• All meta directors deactivate the benzene ring

• The halogens deactivate the benzene ring and direct ortho, para

• Five examples of electrophilic aromatic substitution

o Halogenation – replacement of H by Cl or Br o Nitration – replacement of H by NO2 o Sulfonation – replacement of H by SO3H o Friedel-Crafts alkylation – replacement of H by R o Friedel-Crafts acylation – replacement of H by RCO

• Addition-elimination o The mechanism has two steps o Strong electron-withdrawing groups at the ortho or para positions are

required o Increasing the number of electron-withdrawing groups increases the rate o Increasing the electronegativity of the halogen increases the rate

• Elimination-addition

o Reaction coordinates are harsh o Benzyne is formed as an intermediate o Product mixtures may result

• Other reactions of benzene derivates

Chapter 19

• The carboxylic acid

o Contain a carboxy group (COOH), the central carbon is sp2 hybridized and trigonal planar

o Carboxylic acids are identified by the suffixes -oic acid, carboxylic acid, or -ic acid

o Are polar compounds that exhibit hydrogen bonding interaction

• IR absorptions:

o C=O (1710 cm) o OH (3500-2500 cm)

• H NMR absorptions: o OH (10-12 ppm) o C-H alpha to COOH (2-2.5 ppm)

• C NMR absorption: o C=O (170-210 ppm)

• Carboxylic acids are especially acidic because carboxylate anions are resonance stabilized

• Acidity effects o A carboxylic acid is more acidic than an alcohol or phenol because its

conjugate base is more effectively stabilized by resonance o Acidity increases with the presence of electron-withdrawing groups and

decreased with the presence of a electron-donating groups o Electron-donor groups make a substituted benzoic acid less acidic than

benzoic acid o Electron-withdrawing groups make a substituted benzoic acid more acidic

than benzoic acid

• Preparation of carboxylic acids

o By oxidation of 1 alcohols o By oxidation of alkyl benzenes o By oxidative cleavage of alkynes

Chapter 19 Quick Review

1. What is the IUPAC name of the following compound?

2. Rank the following compounds in order of increasing acidity, putting the least

acidic first.

3. Rank the following compounds in order of increasing acidity, putting the least

acidic first.

4. What two strong absorptions are characteristic of the IR spectrum of carboxylic

acids?

5. At pH 7.0, is benzoic acid mainly existing as a neutral molecule or charged molecule?

Chapter 20

• Aldehydes vs. Ketones o Aldehyde = at least one H atom bonded to the carbonyl group o Ketone = two alkyl or aryl groups bonded to the carbonyl group

o Undergo nucleophilic addition o Aldehydes are MORE reaction (due to being less crowded and less table)

• Carbonyl compounds that contain leaving groups undergo nucleophilic substitution

• Reduction reactions

• Oxidation reactions

• Organometallic reagents (act as a base)

o RLi, RMgX, R2CuLi

o Can react with aldehydes and ketones to form 1, 2, and 3 alcohols

o Can react with esters to form 3 alcohols

o Ca react with acid chlorides to form 3 alcohols or ketones RLi and RMgX (more reactive) add two equivalents of R to an acid

chloride to form a 3 alcohol

R2CuLi (less reactive) only add one equivalent of R to an acid chloride to form a ketone

o React with carbon dioxide to form a carboxylic acid (carboxylation) o React with epoxides to open them up and form an alcohol

• Tert-butyldimethylsilyl ether o Acts as a protecting group

Chapter 20 Quick Review

1. Which reagent can be used to reduce an acid chloride to an aldehyde? a. NaBH4 b. LiAlH(OtBu)3 c. LiAlH4 d. FeCl3

2. What is the product of the following reaction:

3. What is the product of the following reaction:

4. What is the major product of the following reaction:

5. What is the major product of the following reaction:

Chapter 21

• Aldehydes and ketones contain a carbonyl group bonded to only H atoms or R groups. The carbonyl carbon is sp2 hybridized and trigonal planar

• Aldehydes are identified by the suffix -al, whereas ketones are identified by the suffix -one

• Aldehydes and ketones are polar compounds that exhibit dipole-dipole interactions

• Nucleophilic addition reactions

• Reactions going to back ketones and aldehydes

• Spectroscopy

o The carbonyl absorption of cyclic ketones shifts to higher wavelengths as the size of the ring decreases and the ring strain increases

o Conjugation of the carbonyl group with a C = C or a benzene ring shifts the absorption to lower wavenumber by ~30 cm-1

Chapter 21 Quick Review

1. Using 1H NMR spectroscopy, how can you tell the difference between an aldehyde and a ketone?

a. An aldehyde has a C-H stretch (one or two) between 2700-2830 cm-1 b. An aldehyde has a proton signal between 9-10 ppm. c. A ketone has signals around 2-3 ppm. d. A ketone has a signal around 200 ppm.

2. What is the major product from the following sequence of reactions?

3. What is the product of the following reaction?

4. What is the product of the following reaction?

5. What is the product of the following reaction?

Chapter 22

• The characteristic reaction of compounds having the general structure RCOZ is

nucleophilic acyl substitution

• The mechanism consists of two steps: o Addition of a nucleophile to form a tetrahedral intermediate o Elimination of a leaving group

• More reactive acyl compounds can be used to prepare less reactive acyl compounds. The reverse is not necessarily true (but can happen in some cases)

• Reactions of Nitriles

Chapter 22 Quick Review

1. What is the IUPAC name of the following compound?

2. Will the following reaction occur?

3. What is the product of the following reaction?

4. What is the product of the following reaction?

5. What is the product of the following reaction?

Chapter 23

• Kinetic enolate o The less substituted enolate o Favored by strong base, polar aprotic solvent, low temperature; LDA,

THF, -78 C

• Thermodynamic enolate o The more substituted enolate o Favored by strong base, protic solvent, higher temperature: NaOCH2CH3,

CH3CH2OH, room temperature

• Reactions done in acid generally involve enol intermediates

• Reactions done in base generally involve enolate intermediates

• Halogenation at the alpha carbon

• Malonic Ester Synthesis

• Acetoacetic Ester Synthesis

Chapter 23 Quick Review

1. What is the enol form of the following compound?

2. Which of the following compounds is the most acidic?

3. What is the missing reagent in the following reaction?

4. Which is the kinetic enolate of 2-methylcyclohexanone?

5. What is the major product of the following reaction?

Chapter 24

• Aldol Reaction = nucleophilic addition in which an enolate is the nucleophile

o Retro-Aldol Reaction = reverse reaction that occurs with heat in the

presence of base o An aldol reaction between two different carbonyl compounds is called a

crossed aldol or mixed aldol reaction

• Claisen Reaction = nucleophilic substitutions in which an enolate is the nucleophile

o The Dieckmann Reaction = intramolecular Claisen reactions of diesters

form five- and six-membered rings

• Michael Reaction = conjugate addition (1,4-addition) of a resonance-stabilized enolate to the beta carbon of an alpha, beta-unsaturated carbonyl system

o always form a new carbon-carbon bond on the beta carbon of the Michael

acceptors

• Robinson Annulation = ring-forming reaction that combines a Michael reaction an intramolecular aldol reaction

Chapter 24 Quick Review

1. What is the aldol addition product formed from the rection of the following compound with itself?

2. What is the cyclic product formed in the intramolecular Aldol condensation when

the following compound is treated with aqueous NaOH?

3. What reaction type is involved in Claisen reaction?

a. Nucleophilic acyl substitution b. Electrophilic substitution c. Electrophilic addition d. Nucleophilic addition

4. Which of the following statement about Aldol condensation is NOT true?

a. It involves an enolate formation b. It involves a nucleophilic addition reaction c. It involves the loss of a water molecule d. It involves a nucleophilic acyl substitution reaction