Kap 5 Stereochemistry at Tetrahedral Centers

Racemate (Section 5.8):

A mixture consisting of equal parts (1) and (2) enantiomers of a chiral substance; also called a racemic mixture.
Meso compound (Section 5.7)
A compound that contains chirality centers but is nevertheless achiral because it contains a symmetry plane.
Optical activity (Section 5.3)
The rotation of the plane of polarization of plane-polarized light by a chiral substance in solution.

Kap 8 Alkenes: Reactions and Synthesis 262

8.2 Halogenation of Alkenes: Addition of X2 p 264

8.3 Halohydrins from Alkenes: Addition of HOX p. 267

Mechanism of the acid-catalyzed hydration of an alkene to yield an alcohol. P.268

Addition of H2O to alkenes by Oxymercuration p.272

Mechanism

8.5 Hydration of Alkenes: Addition of H2O by Hydroboration p. 273

8.6 Reduction of Alkenes: Hydrogenation p.279

8.9 Addition of Carbenes to Alkenes: Cyclopropane Synthesis

Nonhalogenated cyclopropanes is by a process called the

SimmonsSmith reaction p.289

8.7 Oxidation of Alkenes: Epoxidation and Hydroxylation p.281

P.282

Epoxides undergo an acid-catalyzed ring-opening reaction with water (a hydrolysis)

Hydroxylation: alken syn-diol p.283

8.8 Oxidation of Alkenes: Cleavage to Carbonyl Compounds

Tetrasubst2 ketoner. Trisubst. en keton + en aldehyde. Disubst. 2 aldehyder.

If hydrogens are present on the double bond, carboxylic acids are produced; if two hydrogens are present on one carbon, CO 2
is formed.

Diol karbonyl (aldehyde/keton)

As a general rule, the formation of a new chirality center by the reaction of a chiral reactant leads to unequal amounts of
diastereomeric products. If the chiral reactant is optically active because only one enantiomer is used rather than a
racemic mixture, then the products are also optically active.

Summary Ch 8

Kap. 9 Alkynes

9.4 Hydration of Alkynes: Mercury(II)-Catalyzed Hydration of Alkynes

Mechanism Mercury(II)-Catalyzed Hydration of Alkynes.

HydroborationOxidation of Alkynes

Internal alkyne

Terminal alkyne
Skillnad:

9.5 Reduction of Alkynes

keton

Aldehyde

Li, NH3 mekanism:

9.6 Oxidative Cleavage of Alkynes

9.7 Alkyne Acidity: Formation of Acetylide Anions

9.8 Alkylation of Acetylide Anions

Mek:

The alkylation reaction is limited to the use of primary alkyl bromides and alkyl iodides because acetylide ions are
sufficiently strong bases to cause elimination instead of substitution when they react with secondary and tertiary alkyl
halides.

Kap 10 Organohalides 344

10.6 Reactions of Alkyl Halides: Grignard Reagents

10.7 Organometallic Coupling Reactions Gilman reagents

Kap 11 SN2, SN1, E2, E1 och E1cB

SN2

The Substrate: Steric Effects in the SN2 Reaction

The Nucleophile
Any species, either neutral or negatively charged, can act as a nucleophile as long as it has an unshared pair of electrons; that
is, as long as it is a Lewis base.

Nucleophilicity roughly parallels basicity

Nucleophilicity usually increases going down a column of the periodic table.
Negatively charged nucleophiles are usually more reactive than neutral ones.

The Leaving Group

The best leaving groups are those that best stabilize the negative charge in the transition state. Those groups that best
stabilize a negative charge are also the weakest bases. Thus, weak bases such as Cl2, Br2, and tosylate ion make good leaving
groups, while strong bases such as OH- and NH2- make poor leaving groups.

Para-toluenesulfonyl chloride

The Solvent
Protic solvents those that contain an OH or NH group are generally the worst for SN2 reactions, while polar aprotic
solvents, which are polar but dont have an OH or NH group, are the best.
Acetonitrile (CH3CN), dimethylformamide [(CH3)2NCHO, abbreviated DMF], dimethyl sulfoxide [(CH3)2SO, abbreviated
DMSO], and hexamethylphosphoramide {[(CH3)2N]3PO, abbreviated HMPA} are particularly useful.

SN1

11.5 Characteristics of the SN1 Reaction

The Substrate

The Leaving Group

SN1 of a tertiary alcohol

The Nucleophile
The nature of the nucleophile plays a major role in the SN2 reaction but does not affect an SN1 reaction. Because the SN1
reaction occurs through a rate-limiting step in which the added nucleophile has no part, the nucleophile cant affect the
reaction rate.
The Solvent
SN1 reactions take place much more rapidly in strongly polar solvents, such as water and methanol, than in less polar
solvents, such as ether and chloroform.

E2

11.9 The E2 Reaction and Cyclohexane Conformation

The leaving group and the hydrogen must both be axial for anti periplanar elimination to occur.

11.10 The E1 and E1cB Reactions

The E1cB Reaction

11.12 A Summary of Reactivity: SN1, SN2, E1, E1cB, and E2

Primary alkyl halides SN2 substitution occurs if a good nucleophile is used, E2 eli mination
occurs if a strong, sterically hindered base is used, and E1cB elimination occurs if the leaving
group is t w o carbons a w a y fro m a carbon yl group .
Secondary alkyl halides SN2 substitution occurs if a w eakl y basic nucleophile is used in a polar
aprotic solvent , E2 eli mination predo minates if a strong base is used, and E1cB elimination takes
place if the leaving group is two carbons away fro m a carbonyl group. Secondary allylic and
benzylic alkyl halides can also under go SN1 and E1 reactions if a weakly basic nucleophile is used in
a
solvent.
protic
Tertiary
alkyl halides E2 elimination occurs w hen a base is used, but SN1 substitution and E1
eli mination occur together under neutral conditions, such as in pure ethanol or water. E1cB
eli mination takes place if the leaving group is two carbons away fro m a carbonyl group.

Kap 12 Structure Determination: Mass Spectrometry and Infrared Spectroscopy

424
12.3 Mass Spectrometry
Alcohols

A mines

Carbon yl Co m pounds

12.8 Infrared Spectra of Some Common Functional Groups

Kap 13 Structure Determination: Nuclear Magnetic Resonance Spectroscopy 456

Degreeof unsaturation(HDI )=

2 C +2+ NH X
2

Dr C = kol, N = kvve, H = vte och X = halogen

Kap 14
14.2 Electrophilic Additions to Conjugated Dienes: Allylic Carbocations

14.3 Kinetic versus Thermodynamic Control of Reactions

Electrophilic addition to a conju gated diene at or below roo m te m perature nor mall y leads to a
mi xture of products in w hich the 1,2 adduct predominates o ver the 1,4 adduct.
At higher te m peratures 1,4 adduct predominates.

14.4 The DielsAlder Cycloaddition Reaction

The DielsAlder reaction is that it is stereospecific, meaning that a single product stereoisomer is formed.
Cis-alken cis-produkt
Trans-alken trans-produkt

Kap 15
15.3 Aromaticity and the Huckel 4n+2 Rule
(4n + 2) electrons aro matisk
(4n ) electrons anti- aro matisk

Imidazole, both nitrogens are sp2-hybridized, but one is in a double bond and contributes only one electron to the aromatic
system while the other is not in a double bond and contributes two electrons from its lone pair.

Kap 16 Chemistry of Benzene

16.1 Electrophilic Aromatic Substitution Reactions: Bromination

Aromatic Fluorination, Chlorination, and Iodination

Iodination (Section 16.2)

Aromatic Nitration

Jrn, tenn (Sn) eller SnCl2 kan anvndas som reagens fr att reducera nitrobensen till anilin:

Tin(II) chloride (SnCl2) is particularly mild and is often used when other
reducible functional groups are present.

Aromatic Sulfonation (H2SO4, SO3)

16.3 Alkylation and Acylation of Aromatic Rings: The FriedelCrafts Reaction

FriedelCrafts acylation (Section 16.3)

16.7 Nucleophilic Aromatic Substitution

Nucleophilic aromatic substitution occurs only if the aromatic ring has an electron-withdrawing substituent in a position
ortho or para to the leaving group to stabilize the anion intermediate through resonance.

Note the differences between electrophilic and nucleophilic aromatic substitutions. Electrophilic substitutions are favored
by electron-donating substituents, which stabilize a carbocation intermediate, while nucleophilic substitutions are favored
by electron-withdrawing substituents, which stabilize a carbanion intermediate. Thus, the electron-withdrawing groups
that deactivate rings for electrophilic substitution (nitro, carbonyl, cyano, and so forth) activate them for nucleophilic
substitution. Whats more, these groups are meta directors in electrophilic substitution but are orthopara directors in
nucleophilic substitution. And finally, electrophilic substitutions replace hydrogen on the ring, while nucleophilic
substitutions replace a leaving group, usually halide ion.
16.8 Benzyne

16.9 Oxidation of Aromatic Compounds

O xidation of Alkyl Side Chains
KMnO 4 and Na 2Cr 2O 7

Bromination of Alkylbenzene Side Chains

Bromination occurs exclusively in the benzylic position ne xt to the aro matic rin g and does not gi ve
a mi xture of products.

16.10 Reduction of Aromatic Compounds

Reduction of Aryl Alkyl Ketones

Kap 17 Alcohols and Phenols 620

17.3 Preparation of Alcohols: A Review

17.4 Alcohols from Carbonyl Compounds: Reduction

Reduction of Aldehydes and Ketones

Aldehydes are easily reduced to give primary alcohols, and ketones are reduced to give secondary alcohols.

Reduction of Carboxylic Acids and Esters

Carboxylic acids and esters are reduced to gi ve primary alcohols.

Carboxylic acid and ester reductions are usually carried out with the more reactive reducing agent LiAlH4. All carbonyl
groups, including acids, esters, ketones, and aldehydes, are reduced by LiAlH4.

17.5 Alcohols from Carbonyl Compounds: Grignard Reaction

Carboxylic acids dont give addition products with Grignard reagents because the acidic carboxyl hydrogen reacts with the
basic Grignard reagent to yield a hydrocarbon and the magnesium salt of the acid.

17.6 Reactions of Alcohols

Conversion of Alcohols into Alkyl Halides
Tertiary alcohols react with either HCl or HBr at 0 C by an SN1 mechanism through a carbocation intermediate.

The reactions of primary and secondary alcohols with SOCl2 and PBr3 take place by SN2 mechanisms.

Conversion of Alcohols into Tosylates

Alcohols react with p-toluenesulfonyl chloride (tosyl chloride, p-TosCl) in pyridine solution to yield alkyl tosylates, ROTos.

One of the most important reasons for using tosylates in S N2 reactions is stereochemical. The SN2 reaction of an alcohol via
an alkyl halide proceeds with two inversions of configurationone to make the halide from the alcohol and one to substitute
the halideand yields a product with the same stereochemistry as the starting alcohol. The S N2 reaction of an alcohol via a
tosylate, however, proceeds with only one inversion and yields a product of opposite stereochemistry to the starting alcohol.

Dehydration of Alcohols to Yield Alkenes

Tertiary alcohols

Mekanism:

Alcohol dehydrations carried out with POCl3 in pyridine take place by an E2 mechanism
Mechanism:
Secondary and tertiary alcohols

Alcohol alken E1cB mechanism on a substrate in

which the OH group is two carbons away from a
carbonyl group.

Conversion of Alcohols into Esters

17.7 Oxidation of Alcohols

Primary alcohols yield aldehydes or carboxylic acids, secondary alcohols yield ketones, but tertiary alcohols dont normally
react with most oxidizing agents.

Oxidation of a primary or secondary alcohol KMnO4, CrO3, and Na2Cr2O7, (1*alcohol Dess-Martin
periodinane)

(PCC) Oxidation of a primary or

secondary alcohol Pyridinium chlorochromate (PCC)
PCC is used as an oxidant. In particular, it has proven to be highly effective in oxidizing primary and secondary alcohols to
aldehydes and ketones, respectively.

17.8 Protection of Alcohols

Chlorotrimethylsilane (Cl-TMS) is often used, and the reaction is carried out in the presence of a base, such as
triethylamine, to help form the alkoxide anion from the alcohol and to remove the HCl by-product from the reaction

Ta bort TMS:

17.9 Phenols and Their Uses

Kap 18 Ethers and Epoxides; Thiols and Sulfides

18.2 Synthesis of Ethers

Unfortunately, the method is limited to use with primary alcohols because secondary and tertiary alcohols dehydrate by an
E1 mechanism to yield alkenes.
The Williamson Ether Synthesis

Unsymmetrical ethers should therefore be synthesized by reaction between the more hindered alkoxide partner and less
hindered halide partner rather than vice versa.

Alkoxymercuration of Alkenes
Alken + 1. Hg(OAc)2,H2O 2.NaBH4 alcohol
Alken + 1. (CF3CO2)2Hg, CH3OH 2.NaBH4 Eter

Mekanism:

18.3 Reactions of Ethers: Acidic Cleavage

In fact, ethers undergo only one truly general reactionthey are cleaved by strong acids. Aqueous HBr and HI both work
well, but HCl does not cleave ethers.

Ethers with only primary and secondary alkyl groups react by an SN2 mechanism, in which I2 or Br2 attacks the protonated
ether at the less hindered site.

Ethers with a tertiary, benzylic, or allylic group cleave by either an SN1 or E1 mechanism because these substrates can
produce stable intermediate carbocations.
Mechanism:

18.4 Reactions of Ethers: Claisen Rearrangement

18.5 Cyclic Ethers: Epoxides

18.6 Reactions of Epoxides: Ring-Opening

Acid-Catalyzed Epoxide Opening

Dihydropyran
In organic synthesis, the 2-tetrahydropyranyl group is used as a protecting group for alcohols. Reaction of the alcohol with
dihydropyran forms a tetrahydropyranyl ether, protecting the alcohol from a variety of reactions. The alcohol can later be
restored readily by acidic hydrolysis with formation of 5-hydroxypentanal.

OBS!
When both epoxide carbon atoms are either primary or secondary, attack of the
nucleophile occurs primarily at the less highly substituted sitean SN2-like result. When one of the epoxide carbon atoms is
tertiary, however, nucleophilic attack occurs primarily at the more highly substituted site an SN1-like result.

Base-Catalyzed Epoxide Opening

Base-catalyzed epoxide opening is a typical SN2 reaction in which attack of the nucleophile takes place at the less hindered
epoxide carbon. For example, 1,2-epoxypropane reacts with ethoxide ion exclusively at the less highly substituted, primary,
carbon to give 1-ethoxy-2-propanol.

18.8 Thiols and Sulfides

The reaction often works poorly unless an excess of the nucleophile is used because the product thiol can undergo a second
SN2 reaction with alkyl halide to give a sulfide as a by-product. To circumvent this problem, thiourea, (NH 2)2C P S, is often
used as the nucleophile in the preparation of a thiol from an alkyl halide.

Unlike dialkyl ethers, dialkyl sulfides react rapidly with primary alkyl halides by an SN2 mechanism to give sulfonium ions
(R3S+).

Another difference between sulfides and ethers is that sulfides are easily oxidized. Treatment of a sulfide with hydrogen
peroxide, H2O2, at room temperature yields the corresponding sulfoxide (R2SO), and further oxidation of the sulfoxide with
a peroxyacid yields a sulfone (R2SO2).

Preview of Carbonyl Chemistry

III. General Reactions of Carbonyl Compounds

1. Nucleophilic Addition Reactions of Aldehydes and Ketones (Chapter 19)

2. Nucleophilic Acyl Substitution Reactions of Carboxylic

Acid Derivatives (Chapter 21)

Mechanism

3. Alpha-Substitution Reactions (Chapter 22)

4. Carbonyl Condensation Reactions (Chapter 23)

Carbonyl condensation, takes place w hen two carbonyl compounds react w ith each other Aldol

Mechanism

Kap 19 Aldehydes and Ketones: Nucleophilic Addition Reactions

19.2 Preparing Aldehydes and Ketones
Primary alcohol aldehyde (DessMartin periodinane)

Certain carboxylic acid derivatives can be partially reduced to yield aldehydes. Diisobutylaluminum hydride (DIBAH, or
DIBAL-H)

Preparing Ketones
Either the DessMartin periodinane or a Cr(VI) regent such as CrO3 is a common choice.

19.3 Oxidation of Aldehydes and Ketones

19.4 Nucleophilic Addition Reactions of Aldehydes and Ketones

19.5 Nucleophilic Addition of H2O: Hydration

Mekanism; basisk

Mechanism; sur

19.6 Nucleophilic Addition of HCN: Cyanohydrin Formation

19.7 Nucleophilic Addition of Hydride and Grignard Reagents: Alcohol Formation

Addition of Hydride Reagents: Reduction

Addition of Grignard Reagents, RMgX

Mekanism:

19.8 Nucleophilic Addition of Amines: Imine and Enamine Formation

Mechanism of imine formation. Primary amine. Acid-catalyzed process

Mechanism of enamine. An aldehyde or ketone with a secondary amine, R2NH. Acid-catalyst

19.9 Nucleophilic Addition of Hydrazine: The WolffKishner Reaction: reduction of an aldehyde or ketone
to yield an alkane.

Mechanism Wolff-Kishner

19.10 Nucleophilic Addition of Alcohols: Acetal Formation

Mechanism of acid-catalyzed acetal formation by reaction of an aldehyde or

ketone with an alcohol.

19.11 Nucleophilic Addition of Phosphorus Ylides: The Wittig Reaction

PCl5 will convert carboxylic acids to the corresponding acyl chloride. It also converts alcohols to alkyl chloride. SOCl2 is
more commonly used in the laboratory because the SO2 is more easily separated from the organic products than is POCl 3.

19.13 Conjugate Nucleophilic Addition to , unsaturated Aldehydes and Ketones

The net effect is addition of the nucleophile to the C=C bond, with the carbonyl group itself unchanged. In fact, of course,
the carbonyl group is crucial to the success of the reaction. The C=C bond would not be activated for addition, and no
reaction would occur, without the carbonyl group.

Conjugate Addition of Amines

Reaktionen ovan sker under termodynamisk kontroll och inte kinetisk kontroll. Drfr bildas endast den mest stabila
konjugat additionsprodukt.
Conjugate Addition of Alkyl Groups: Organocopper Reactions
Only ketones, not aldehydes

Mechanism:

Kap 20 Karboxylsyror & Nitriler

20.5 Preparing Carboxylic Acids

Oxidation of a substituted alkylbenzene with KMnO4 or
Na2Cr2O7 gives a substituted benzoic acid (Section 16.9).

Alcohol & aldehyde carboxylic acid

Hydrolysis of Nitriles
Note that the product acid has one more carbon than the starting alkyl halide.

Carboxylation of Grignard Reagents

Exempel

20.6 Reactions of Carboxylic Acids: An Overview

Preparation of Nitriles
The simplest method of nitrile preparation is the S N2 reaction of CN with a primary or secondary alkyl halide, as discussed
in Section 20.5.
Primary amide, RCONH2 + SOCl2 eller POCl3 nitriles

Mechanism:

Reactions of Nitriles

Hydrolysis: Conversion of Nitriles into Carboxylic Acids

OBS! Se section 21.7

Step 4 (21.7)

Reduction: Conversion of Nitriles into Amines

NH2

Mechanism:

Reaction of Nitriles with Grignard Reagents

The mechanism of the hydrolysis is the exact reverse of imine formation.

Kap 21Carboxylic Acid Derivatives: Nucleophilic Acyl Substitution Reactions

21.2 Nucleophilic Acyl Substitution Reactions

21.3 Nucleophilic Acyl Substitution Reactions of Carboxylic Acids

Conversion of Carboxylic Acids into Acid Chlorides

Mechanism:

Conversion of Carboxylic Acids into Esters

Fischer esterification reaction

Unfortunately, the need to use an excess of a liquid alcohol as solvent effectively limits the method to the synthesis of
methyl, ethyl, propyl, and butyl esters.

Mechanism:

Conversion of Carboxylic Acids into Amides

Amides are difficult to prepare by direct reaction of carboxylic acids with amines because amines are bases that convert
acidic carboxyl groups into their unreactive carboxylate anions. Thus, the OH must be replaced by a better, nonacidic
leaving group. Dicyclohexylcarbodiimide (DCC) is used.

Conversion of Carboxylic Acids into Alcohols

Alternatively, borane in tetrahydrofuran (BH3/THF) is a useful reagent for reducing carboxylic acids to primary alcohols.
Reaction of an acid with BH3/THF occurs rapidly at room temperature, and the procedure is often preferred to reduction with
LiAlH4 because of its relative ease and safety.

LiAlH4 hade reducerat bde karboxylsyra och nitrogrupp (NO2)

21.4 Chemistry of Acid Halides

Jmf

Reactions of Acid Halides

Conversion of Acid Halides into Acids: Hydrolysis

Because HCl is formed during the hydrolysis, the reaction is often carried out in the presence of a base such as pyridine or
NaOH to remove the HCl and prevent it from causing side reactions.
Conversion of Acid Halides into Anhydrides

Both symmetrical and unsymmetrical acid anhydrides can be prepared.

Conversion of Acid Halides into Esters: Alcoholysis

Conversion of Acid Halides into Amides: Aminolysis

Because HCl is formed during the reaction, 2 equivalents of the amine must be used.

Conversion of Acid Chlorides into Alcohols: Reduction and Grignard Reaction

Conversion of Acid Chlorides into Ketones: Diorganocopper Reaction

Note that the diorganocopper reaction occurs only with acid chlorides. Carboxylic acids, esters, acid anhydrides, and amides
do not react with lithium diorganocopper reagents.

21.5 Chemistry of Acid Anhydrides

Preparation of Acid Anhydrides
Both symmetrical and unsymmetrical acid anhydrides can be prepared in this way.

Reactions of Acid Anhydrides

Conversion of Acid Anhydrides into Esters

Conversion of Acid Anhydrides into Amides

Mechanism:

Ex 2

21.6 Chemistry of Esters

Reactions of Esters
Esters undergo the same kinds of reactions that weve seen for other carboxylic acid derivatives, but they are less reactive
toward nucleophiles than either acid chlorides or anhydrides. All their reactions are applicable to both acyclic and cyclic
esters, called lactones.

Conversion of Esters into Carboxylic Acids: Hydrolysis

Mekanism: Ester hydrolysis in basic solution is called saponification. Aqueous base or acid.

Mechanism of acid-catalyzed ester hydrolysis. Reverse of Fischer esterification

Conversion of Esters into Amides: Aminolysis

The reaction is not often used, however, because its usually easier to prepare an amide by starting with an acid chloride
(Section 21.4).

Conversion of Esters into Alcohols: Reduction

Mechanism:

Ester aldehyde

Conversion of Esters into Alcohols: Grignard Reaction

Esters react with 2 equivalents of a Grignard reagent to yield a tertiary alcohol in which two of the substituents are identical
(Section 17.5).

21.7 Chemistry of Amides

Amides are the least reactive of the common acid derivatives and undergo relatively few nucleophilic acyl substitution
reactions.
Preparation of Amides

Reactions of Amides
Conversion of Amides into Carboxylic Acids: Hydrolysis
Amides undergo hydrolysis to yield carboxylic acids plus ammonia or an amine on heating in either aqueous acid or aqueous
base.
Syra-katalys:

Bas-katalys:

Conversion of Amides into Amines: Reduction

This kind of reaction is specific for amides and does not occur with other carboxylic acid derivatives.

Mechanism:

Ex

Uppg 21.21

Solution

Ch. 22 Carbonyl Alpha-Substitution Reactions

22.1 KetoEnol Tautomerism

Note the difference between tautomers and resonance forms. Tautomers are constitutional isomers different compounds with
different structures while resonance forms are different representations of a single compound. Tautomers have their atoms
arranged differently, while resonance forms differ only in the position of their and nonbonding electrons.

Mechanism of enol formation under both acid-catalyzed and base-catalyzed conditions

Note that only the hydrogens on the -position of carbonyl compounds are acidic. Hydrogens at , , , and so on, arent
acidic and cant be removed by base because the resulting anions cant be resonance- stabilized by the carbonyl group.
22.2 Reactivity of Enols: The Mechanism of Alpha-Substitution Reactions

22.3 Alpha Halogenation of Aldehydes and Ketones

Cl2, Br2 eller I2 i sur lsning p aldehyders och ketoners -position.
(acetic acid)

Mekanism:

Uppg 22.5 Show how you might prepare 1-penten-3-one from 3-pentanone.

22.4 Alpha Bromination of Carboxylic Acids

HellVolhardZelinskii (HVZ) reaction

Mekanism:

Acid Halides into Acids: Hydrolysis

Alcohols into Alkyl Halides

Carboxylic Acids into Acid Chlorides

22.5 Acidity of Alpha Hydrogen Atoms: Enolate Ion Formation

In practice, the strong base lithium diisopropylamide [LiN(i-C3H7)2; abbreviated LDA] is commonly used for making enolate
ions.

Many types of carbonyl compounds, including aldehydes, ketones, esters, thioesters, acids, and amides, can be converted
into enolate ions by reaction with LDA.

22.6 Reactivity of Enolate Ions

22.7 Alkylation of Enolate Ions

Haloform Reaction

The Malonic Ester Synthesis

The malonic ester synthesis, a method for preparing a carboxylic acid from an alkyl halide while lengthening the carbon
chain by two atoms.

The product of a malonic ester alkylation has one acidic hydrogen remaining, so the alkylation process can be repeated to
yield a dialkylated malonic ester.

On heating with aqueous hydrochloric acid, the alkylated (or dialkylated) malonic ester undergoes hydrolysis of its two ester
groups followed by decarboxylation (loss of CO2) to yield a substituted monocarboxylic acid.

Only substituted malonic acids and -keto acids undergo loss of CO2 on heating (decarboxylation).

Exempel:

The malonic ester synthesis can also be used to prepare cycloalkanecarboxylic acids.
Ex:

The Acetoacetic Ester Synthesis

The acetoacetic ester synthesis converts an alkyl halide into a methyl ketone having three more carbons.

Decarboxylation:

Direct Alkylation of Ketones, Esters, and Nitriles

Ketones, esters, and nitriles can all be alkylated using LDA or related dialkylamide bases in THF.

Kap 23 Carbonyl Condensation Reactions

23.1 Carbonyl Condensations: The Aldol Reaction
The general mechanism of a carbonyl condensation reaction. Carbonyl condensation reactions take place between two
carbonyl partners. One partner becomes a nucleophilic donor and adds to the second partner as an electrophilic acceptor.
After protonation, the final product is a -hydroxy carbonyl compound.

Problem 23.1
Predict the aldol reaction product of the following compounds:

23.2 Carbonyl Condensations versus Alpha Substitutions

Alpha-substitution reactions require a full equivalent of strong base and are normally carried out so that the carbonyl
compound is rapidly and completely converted into its enolate ion at a low temperature. An electrophile is then added rapidly
to ensure that the reactive enolate ion is quenched quickly.

On the other hand, carbonyl condensation reactions require only a catalytic amount of a relatively weak base rather than a
full equivalent so that a small amount of enolate ion is generated in the presence of unreacted carbonyl compound.

23.3 Dehydration of Aldol Products: Synthesis of Enones

The real value of aldol dehydration is that removal of water from the reaction mixture can be used to drive the aldol
equilibrium toward product.

23.4 Using Aldol Reactions in Synthesis

The aldol reaction yields either a -hydroxy aldehyde/ketone or an ,-unsaturated aldehyde/ketone, depending on the
experimental conditions. Whenever the target molecule contains either a -hydroxy aldehyde/ketone or a conjugated
enone functional group, it might come from an aldol reaction.

23.5 Mixed Aldol Reactions

In general, a mixed aldol reaction between two similar aldehyde or ketone partners leads to a mixture of four possible
products. For example, base treatment of a mixture of acetaldehyde and propanal gives a complex product mixture
containing two symmetrical aldol products and two mixed aldol products.

On the other hand, mixed aldol reactions can lead cleanly to a single product if either of two conditions is met:
If one of the carbonyl partners contains no hydrogens, and thus cant form an enolate ion to become a donor, but does
contain an unhindered carbonyl group and so is a good acceptor of nucleophiles, then a mixed aldol reaction is likely to
be successful.
Example:

If one of the carbonyl partners is much more acidic than the other and so is transformed into its enolate ion in preference
to the other, then a mixed aldol reaction is likely to be successful.
Example:

23.6 Intramolecular Aldol Reactions

When certain dicarbonyl compounds are treated with base an intramolecular aldol reaction can occur, leading to the
formation of a cyclic product.

Solution:

23.7 The Claisen Condensation Reaction

Esters, like aldehydes and ketones, are weakly acidic. When an ester with an hydrogen is treated with 1 equivalent of a
base such as sodium ethoxide, a reversible carbonyl condensation reaction occurs to yield a -keto ester.

Mekanism:

The only difference between the aldol condensation of an aldehyde or ketone and the Claisen condensation of an ester
involves the fate of the initially formed tetrahedral intermediate. The tetrahedral intermediate in the aldol reaction is
protonated to give an alcohol product exactly the behavior previously seen for aldehydes and ketones (Section 19.4). The
tetrahedral intermediate in the Claisen reaction, however, expels an alkoxide leaving group to yield an acyl substitution
product exactly the behavior previously seen for esters (Section 21.6).
Problem 23.12
As shown in Figure 23.4, the Claisen reaction is reversible. That is, a -keto ester can be cleaved by base into two fragments.
Using curved arrows to indicate electron flow, show the mechanism by which this cleavage occurs.

Solution:

23.8 Mixed Claisen Condensations

Mixed Claisen reactions are successful only when one of the two ester components has no hydrogens and thus cant form
an enolate ion.

Mixed Claisen-like reactions

Can also be carried out between an ester and a ketone, resulting in the synthesis of a -diketone. The reaction works best
when the ester component has no hydrogens and thus cant act as the nucleophilic donor.

23.9 Intramolecular Claisen Condensations: The Dieckmann Cyclization

Intramolecular Claisen condensations can be carried out with diesters, just as intramolecular aldol condensations can be
carried out with diketones (Section 23.6).

The cyclic -keto ester produced in a Dieckmann cyclization can be further alkylated and decarboxylated by a series of
reactions analogous to those used in the acetoacetic ester synthesis (Section 22.7).
The overall sequence of (1) Dieckmann cyclization, (2) -keto ester alkylation, and (3) decarboxylation is a powerful method
for preparing 2-substituted cyclopentanones and cyclohexanones.

(2)
(22.7 Alkylation of Enolate Ions

(3)

23.10 Conjugate Carbonyl Additions: The Michael Reaction

The best Michael reactions are those that take place when a particularly stable enolate ion such as that derived from a -keto
ester or other 1,3-dicarbonyl compound adds to an unhindered ,-unsaturated ketone.

23.11 Carbonyl Condensations with Enamines: The Stork Reaction

(1) Enamine formation from a ketone (sid 50 word). (2) The enamine adds to the ,-unsaturated ketone in a Michael
reaction (ovan p denna sida). (3) Enamine hydrolysis back to a ketone (sid 50).

23.12 The Robinson Annulation Reaction: (Aldol reaction)

The Robinson annulation is a two-step process that combines a Michael reaction with an intramolecular aldol reaction. It
takes place between a nucleophilic donor, such as a -keto ester, an enamine, or a -diketone, and an ,-unsaturated
ketone acceptor, such as 3-buten-2-one. The product is a substituted 2-cyclohexenone.

Kap 24 Amines and Heterocycles

24.4 Basicity of Arylamines
Arylamines are generally less basic than alkylamines. Arylamines are less basic than alkylamines because the nitrogen lonepair electrons are delocalized by interaction with the aromatic ring electron system and are less available for bonding to
H+.

24.6 Synthesis of Amines

Reduction of Nitriles, Amides, and Nitro Compounds

Tin(II) chloride (SnCl2) is particularly mild and is often used when other reducible functional groups are present.
SN2 Reactions of Alkyl Halides

Unfortunately, these reactions dont stop cleanly after a single alkylation has occurred. Because ammonia and primary
amines have similar reactivity, the initially formed monoalkylated substance often undergoes further reaction to yield a
mixture of products.
Ex:

Reductive Amination of Aldehydes and Ketones

Azide ion ()
A better method for preparing primary amines is to use azide ion, N3-, as the nucleophile rather than ammonia for SN2
reaction with a primary or secondary alkyl halide. The product is an alkyl azide, which is not nucleophilic, so overalkylation
cant occur.

Gabriel amine synthesis

Mechanism; sista steg

Reductive Amination of Aldehydes and Ketones

Mechanism:

Ammonia adds to the ketone carbonyl group in a nucleophilic addition reaction to yield an intermediate carbinolamine.
The carbinolamine loses water to give an imine.
product.

The imine is reduced by NaBH4 or H2/Ni to yield the amine

NB: Its usually better to choose the combination with the simpler amine component methylamine in this case and to use an
excess of that amine as reactant.
Hofmann and Curtius Rearrangements
Carboxylic acid derivatives can be converted into primary amines with loss of one carbon atom by both the Hofmann
rearrangement and the Curtius rearrangement. Although the Hofmann rearrangement involves a primary amide and the
Curtius rearrangement involves an acyl azide, both proceed through similar mechanisms.

Hofmann Mechanism:

(1) Base abstracts an acidic N-H proton, yielding an amide anion. (2) The anion reacts with bromine in an alpha-substitution
reaction to give an N-bromoamide. (3) Abstraction of the remaining NH proton by base gives a resonance-stabilized
bromoamide anion . . . (4) . . . which rearranges when the R group attached to the carbonyl carbon migrates to nitrogen at the
same time the bromide ion leaves. (5) The isocyanate formed on rearrangement adds water in a nucleophilic addition step to
yield a carbamic acid. (6) The carbamic acid spontaneously loses CO2 to give an amine.

Curtius mechanism

Ex:

24.7 Reactions of Amines

(Sections 21.4 and 21.5) Primary and secondary (but not tertiary) amines can also be acylated by nucleophilic acyl
substitution reaction with an acid chloride or an acid anhydride to yield an amide.

Hofmann Elimination
Like alcohols, amines can be converted into alkenes by an elimination reaction. But because an amide ion, NH 2-, is such a
poor leaving group, it must first be converted into a better leaving group.

Silver oxide acts by exchanging iodide ion for hydroxide ion in the quaternary salt, thus providing the base necessary for
elimination. The actual elimination step is an E2 reaction (Section 11.8) in which hydroxide ion removes a proton at the same
time that the positively charged nitrogen atom leaves.
Unlike what happens in other E2 reactions, the major product of the Hofmann elimination is the less highly substituted
alkene rather than the more highly substituted one.

Ex p Hofmann elimination:
1.

2.

24.8 Reactions of Arylamines

This high reactivity of amino-substituted benzenes can be a drawback at times because its often difficult to prevent
polysubstitution.
Ex:

Another drawback to the use of amino-substituted benzenes in electrophilic aromatic substitution reactions is that Friedel
Crafts reactions are not successful (Section 16.3). The amino group forms an acidbase complex with the AlCl3 catalyst,
which prevents further reaction from occurring. Both drawbacks can be overcome, however, by carrying out electrophilic
aromatic substitution reactions on the corresponding amide rather than on the free amine.

Ex:

Ex:

Diazonium Salts: The Sandmeyer Reaction

Primary arylamines react with nitrous acid, HNO2 salpetersyrlighet, to yield stable arenediazonium salts,
a process called a diazotization reaction.

Arenediazonium salts are useful because the diazonio group (N2) can be replaced by a nucleophile in a substitution reaction.

Many different nucleophileshalide, hydride, cyanide, and hydroxide among othersreact with arenediazonium salts,
yielding many different kinds of substituted benzenes. The overall sequence of (1) nitration, (2) reduction, (3) diazotization,
and (4) nucleophilic substitution is perhaps the single most versatile method of aromatic substitution.
Sandmeyer reaction

Aryl chlorides and bromides are prepared by reaction of an arenediazonium salt with the corresponding copper(I) halide,
CuX. Aryl iodides can be prepared by direct reaction with NaI without using a copper(I) salt.

Nitriles:
Similar treatment of an arenediazonium salt with CuCN yields the nitrile, ArCN, which can then be further converted into
other functional groups such as carboxyl.

OH

H: med hjlp av H3PO2 hypofosforsyra

Diazonium Coupling Reactions

Azo compounds,
.

Mechanism:

Kap 25 Biomolecules: Carbohydrates

25.5 Cyclic Structures of Monosaccharides: Anomers
By convention, the rings are usually drawn by placing the hemiacetal oxygen atom at the right rear. Note that an OH
group on the right in a Fischer projection is on the bottom face of the pyranose ring, and an OH group on the left in a
Fischer projection is on the top face of the ring. For D sugars, the terminal CH2OH group is on the top of the ring, whereas
for L sugars, the CH2OH group is on the bottom.

The compound with its newly generated OH group at C1 cis to the OH at the lowest chirality center in a Fischer
projection is called the anomer; its full name is -D-glucopyranose. The compound with its newly generated OH group
trans to the OH at the lowest chirality center in a Fischer projection is called the anomer; its full name is -Dglucopyranose.
Note that in -D-glucopyranose, all the substituents on the ring are equatorial. Thus, -D-glucopyranose is the least sterically
crowded and most stable of the eight D aldohexoses.

25.6 Reactions of Monosaccharides

Ester and Ether Formation

Glycoside Formation

Reduction of Monosaccharides

Oxidation of Monosaccharides

Chain Lengthening: The KilianiFischer Synthesis

Chain Shortening: The Wohl Degradation

Kap 30 Orbitals and Organic Chemistry: Pericyclic Reactions

Pericyclic reaction
A pericyclic reaction is one that occurs by a concerted process through a cyclic transition state. The word concerted means
that all bonding changes occur simultaneously; no intermediates are involved.
30.1 Molecular Orbitals of Conjugated Pi Systems
Those molecular orbitals with fewer nodes are lower in energy than the isolated p atomic orbitals and are bonding MOs;
those molecular orbitals with more nodes are higher in energy than the isolated p orbitals and are antibonding MOs.

30.2 Electrocyclic Reactions

An electrocyclic reaction is a pericyclic process that involves the cyclization of a conjugated acyclic polyene. One bond is
broken, the other bonds change position, a new bond is formed, and a cyclic compound results.

In general, the triene cyclohexadiene equilibrium favors the cyclic product, whereas the diene cyclobutene equilibrium
favors less strained open-chain product.

30.3 Stereochemistry of Thermal Electrocyclic Reactions

30.4 Photochemical Electrocyclic Reactions

Kap 26 Biomolecules: Amino Acids, Peptides and Proteins

26.7 Peptide Synthesis
A simple amide might be formed by treating an amine and a carboxylic acid with dicyclohexylcarbodiimide (DCC; Section
21.7), but peptide synthesis is a more difficult problem because many different amide bonds must be formed in a specific
order rather than at random.
The solution to the specificity problem is protection (Section 17.8). If we want to couple alanine with leucine to synthesize
Ala-Leu, for instance, we could protect the ] NH2 group of alanine and the ] CO2H group of leucine to shield them from
reacting, then form the desired Ala-Leu amide bond by reaction with DCC, and then remove the protecting groups.
Carboxyl groups are often protected simply by converting them into methyl or benzyl esters. Both groups are easily
introduced by standard methods of ester formation (Section 21.6) and are easily removed by mild hydrolysis with aqueous
NaOH. Benzyl esters can also be cleaved by catalytic hydrogenolysis of the weak benzylic C-O bond (RCO2 CH2Ph + H2
RCO2H + PhCH3).

Amino groups are often protected as their tert-butyloxycarbonyl amide (Boc) or fluorenylmethyloxycarbonyl amide (Fmoc)
derivatives. The Boc protecting group is introduced by reaction of the amino acid with di-tert-butyl dicarbonate in a
nucleophilic acyl substitution reaction and is removed by brief treatment with a strong acid such as trifluoroacetic acid,
CF3CO2H. The Fmoc protecting group is introduced by reaction with an acid chloride and is removed by treatment with
base.

Thus, five steps are needed to synthesize a dipeptide such as Ala-Leu:

Determining relative acidity and basicity

A BrnstedLowry acid is a substance that donates a hydrogen ion, H+.
BrnstedLowry base is a substance that accepts a hydrogen ion.
A Lewis acid is a substance that accepts an electron pair.
Lewis base is a substance that donates an electron pair.
Acids
When determining the acidity of two acids, evaluate the relative stabilities of their conjugate bases acid after donating the
proton (H) by considering these factors:

Bases
When determining the basicity of two bases, evaluate the relative stabilities of the bases themselves.

Evaluate which of the two or more bases is better able to donate its lone pair of electrons?
Electronegativity; the more electronegative atom will hold on its electrons more tightly than the atom that is less e-negative.