ORGANIC CHEMISTRY - CHAPTER 21: AMINES AND THEIR DERIVATIVES

ORGANIC CHEMISTRY - CHAPTER 20: CARBOXYLIC ACIDS DERIVATIVES

New Reactions

Important Concepts

1.  The electrophilic reactivity of the carbonyl carbon in carboxylic acid derivatives is weakened by good electron-donating substituents. This effect, measurable by IR spectroscopy, is responsible not only for the decrease in the reactivity with nucleophiles and acid, but also for the increased basicity along the series: acyl halides – anhydrides – esters – amides. Electron donation by resonance from the nitrogen in amides is so pronounced that there is hindered rotation about the amide bond on the NMR time scale.

2.  Carboxylic acid derivatives are named as acyl halides, carboxylic anhydrides, alkyl alkanoates, alkanamides, and alkanenitriles, depending on the functional group.

3.  Carbonyl stretching frequencies in the IR spectra are diagnostic of the carboxylic acid derivatives: Acyl chlorides absorb at 1790 – 1815 cm^-1, anhydrides at 1740 – 1790 and 1800 – 1850 cm^-1, esters at 1735 – 1750 cm^-1, and amides at 1650 – 1690 cm^-1.

4. Carboxylic acid derivatives generally react with water (under acid or base catalysis) to hydrolyze to the corresponding carboxylic acid; they combine with alcohols to give esters and with amines to furnish amides. With Grignard and other organometallic reagents, they form ketones; esters may react further to form the corresponding alcohols. Reduction by hydrides gives products in various oxidation states: aldehydes, alcohols, or amines.

5.  Long-chain esters are the constituents of animal and plant waxes.Triesters of glycerol are contained in natural oils and fats. Their hydrolysis gives soaps. Triglycerides containing phosphoric acid ester subunits belong to the class of phospholipids. Because they carry a highly polar head group and hydrophobic tails, phospholipids form micelles and lipid bilayers.

6.  Transesterification can be used to convert one ester into another.

7.  The functional group of nitriles is somewhat similar to that of the alkynes. The two component atoms are sp hybridized. The IR stretching vibration appears at about 2250 cm^-1. The hydrogens next to the cyano group are deshielded in ¹H NMR. The ¹³C NMR absorptions for nitrile carbons are at relatively low field (δ, 112 – 126 ppm), a consequence of the electronegativity of nitrogen.

From "Organic Chemistry" Textbook of VOLLHARDT & SCHORE

ORGANIC CHEMISTRY - CHAPTER 19: CARBOXYLIC ACIDS

Important Concepts

1.  Carboxylic acids are named as alkanoic acids. The carbonyl carbon is numbered 1 in the longest chain incorporating the carboxy group. Dicarboxylic acids are called alkanedioic acids. Cyclic and aromatic systems are called cycloalkane carboxylic and benzoic acids, respectively.  In these systems the ring carbon bearing the carboxy group is assigned the number 1.

2.  The carboxy group is approximately trigonal planar. Except in very dilute solution, carboxylic acids form dimers by hydrogen bonding.

3.  The carboxylic acid proton chemical shift is variable but relatively high (δ = 10 – 13),  because of hydrogen bonding. The carbonyl carbon is also relatively deshielded but not as much as in aldehydes and ketones, because of the resonance contribution of the hydroxy group. The carboxy function shows two important infrared bands, one at about 1710 cm^-1 for the C=O bond and a very broad band between 2500 and 3300 cm^-1 for the O – H group. The mass spectrum of carboxylic

acids shows facile fragmentation in three ways.

4.  The carbonyl group in carboxylic acids undergoes nucleophilic displacement via the addition – elimination pathway. Addition of a nucleophile gives an unstable tetrahedral intermediate that decomposes by elimination of the hydroxy group to give a carboxylic acid derivative.

5.  Lithium aluminum hydride is a strong enough nucleophile to add to the carbonyl group of carboxylate ions. This process allows the reduction of carboxylic acids to primary alcohols.

From "Organic Chemistry" Textbook of VOLLHARDT & SCHORE

ORGANIC CHEMISTRY - CHAPTER 18: ENOLS, ENOLATES AND THE ALDOL CONDENSATION

Important Concepts

1.  Hydrogens next to the carbonyl group (α-hydrogens) are acidic because of the electron-withdrawing nature of the functional group and because the resulting enolate ion is resonance stabilized.

2.  Electrophilic attack on enolates can occur at both the α-carbon and the oxygen. Haloalkanes usually prefer the α-carbon. Protonation of the oxygen leads to enols.

3.  Enamines are neutral analogs of enolates. Resonance donation of the nitrogen lone pair imparts nucleophilic character on the remote double bond carbon, which can be alkylated to give iminium cations that hydrolyze to aldehydes and ketones on aqueous work-up.

4.  Aldehydes and ketones are in equilibrium with their tautomeric enol forms; the enol – keto conversionis catalyzed by acid or base. This equilibrium allows for facile a-deuteration and stereochemical equilibration.

5.  A-Halogenationof carbonyl compounds may be acid or base catalyzed. With acid, the enol is halogenated by attack at the double bond; subsequent renewed enolization is slowed down by the halogen substituent. With base, the enolate is attacked at carbon, and subsequent enolate formation is accelerated by the halogens introduced.

6.  Enolates are nucleophilic and reversibly attack the carbonyl carbon of an aldehyde or a ketone in the aldol condensation. They also attack the β-carbon of an α,β-unsaturated carbonyl compound in the Michael addition.

7.  α,β-Unsaturated aldehydes and ketones show the normal chemistry of each individual double bond, but the conjugated system may react as a whole, as revealed by the ability of these compounds to undergo acid- and base-mediated 1,4-additions. Cuprates add in 1,4-manner, whereas alkyllithiums normally attack the carbonyl function.

From "Organic Chemistry" Textbook of VOLLHARDT &SCHORE

ORGANIC CHEMISTRY - CHAPTER 17: ALDEHYDES AND KETONES

New Reaction

Important Concepts

1. The carbonyl group is the functional group of the aldehydes (alkanals) and ketones (alkanones). It has precedence over the hydroxy, alkenyl, and alkynyl groups in the naming of molecules.

2. The carbon – oxygen double bond and its two attached nuclei in aldehydes and ketones form a plane. The C=O unit is polarized,with a partial negative charge on oxygen and a partial positive charge on carbon.

3. The ¹H NMR spectra of aldehydes exhibit a peak at δ ≈ 9.8 ppm. In ¹³C NMR, the carbonyl carbon absorbs at ~200 ppm. Aldehydes and ketones have strong infrared bands in the region 1690 – 1750 cm^-1; this absorption is due to the stretching of the C=O bond. Because of the avail-ability of low-energy n → π* transitions, the electronic spectra of aldehydes and ketones have relatively long wavelength bands. This class of compounds displays characteristic mass spectral fragmentations around the carbonyl function.

4. The carbon – oxygen double bond undergoes ionic additions.The catalysts for these processes are acids and bases.

5. The reactivity of the carbonyl group increases with increasing electrophilic character of the carbonyl carbon. Therefore, aldehydes are more reactive than ketones.

6. Primary amines undergo condensation reactions with aldehydes and ketones to imines; secondary amines condense to enamines.

7. The combination of Friedel-Crafts acylation and Wolff-Kishner or Clemmensen reduction allows synthesis of alkylbenzenes free of the limitations of Friedel-Crafts alkylation.

8. The Wittig reaction is an important carbon – carbon bond-forming reaction that produces alkenes directly from aldehydes and ketones.

9. The reaction of peroxycarboxylic acids with the carbonyl group of ketones produces esters.

From "Organic Chemistry" Textbook of VOLLHARDT & SCHORE

ORGANIC CHEMISTRY - CHAPTER 16: ELECTROPHILIC ATTACK ON DERIVATIVES OF BENZENE

New Reactions

Important Concepts

1.  Substituents on the benzene ring can be divided into two classes: those that activate the ring by electron donation and those that deactivate it by electron withdrawal. The mechanisms of donation and withdrawal are based on induction or resonance. These effects may operate simultaneously to either reinforce or oppose each other. Amino and alkoxy substituents are strongly activating, alkyl and phenyl groups weakly so; nitro, trifluoromethyl, sulfonyl, oxo, nitrile, and cationic groups are strongly deactivating, whereas halogens are weakly so.

2. Activators direct electrophiles ortho and para; deactivators direct meta, although at a much lower rate. The exceptions are the halogens,which deactivate but direct ortho and para.

3. When there are several substituents, the strongest activator (or weakest deactivator) controls the regioselectivity of attack, the extent of control decreasing in the following order: NR2, OR > X₂, R > meta directors

4. Strategies for the synthesis of highly substituted benzenes rely on the directing power of the substituents, the synthetic ability to change the sense of direction of these substituents by chemical manipulation, and the use of blocking and protecting groups.

5. Naphthalene undergoes preferred electrophilic substitution at C1 because of the relative stability of the intermediate carbocation.

6. Electron-donating substituents on one of the naphthalene rings direct electrophiles to the same ring, ortho and para. Electron-withdrawing substituents direct electrophiles away from that ring; substitution is mainly at C5 and C8.

7.The actual carcinogen derived from benzo[a]pyrene appears to be an oxacyclopropanediol in which C7 and C8 bear hydroxy groups and C9 and C10 are bridged by oxygen. This molecule alkylates one of the nitrogens of one of the DNA bases, thus causing mutations.

From "Organic Chemistry" Textbook of VOLLHARDT & SCHORE

ORGANIC CHEMISTRY - CHAPTER 15: BENZENE AND AROMATICITY

Important Concepts

1. Substituted benzenes are named by adding prefixes or suffixes to the word benzene. Disubstituted 

systems are labeled as 1,2-, 1,3-, and 1,4- or ortho, meta, and para, depending on the location of the substituents. Many benzene derivatives have common names, sometimes used as bases for naming their substituted analogs. As a substituent, an aromatic system is called aryl; the parent aryl substituent, C₆H₅, is called phenyl; its homolog C₆H₅CH₂ is named phenylmethyl (benzyl).

2. Benzene is not a cyclohexatriene but a delocalized cyclic system of six π electrons. It is a regular hexagon of six sp²-hybridized carbons. All six p orbitals overlap equally with their neighbors. Its unusually low heat of hydrogenation indicates a resonance energy or aromaticity of about 30 kcal mol^-1 (126 kJ mol^-1). The stability imparted by aromatic delocalization is also evident in the transition state of some reactions, such as the Diels-Alder cycloaddition and ozonolysis.

3. The special structure of benzene gives rise to unusual UV,  IR,  and NMR spectral data. ¹H NMR spectroscopy is particularly diagnostic because of the unusual deshielding of aromatic hydrogens by an induced ring current. Moreover,  the substitution pattern is revealed by examination of the o,  m, and p coupling constants.

4. The polycyclic benzenoid hydrocarbons are composed of linearly or angularly fused benzene rings. The simplest members of this class of compounds are naphthalene, anthracene, and phenanthrene.

5.  In these molecules, benzene rings share two (or more) carbon atoms, whose π  electrons are delocalized over the entire ring system. Thus, naphthalene shows some of the properties characteristic of the aromatic ring in benzene: The electronic spectra reveal extended conjugation, ¹H NMR exhibits deshielding ring-current effects, and there is little bond alternation.

6. Benzene is the smallest member of the class of aromatic cyclic polyenes following Hückel’s 

(4n + 2) rule. Most of the 4n π systems are relatively reactive anti- or nonaromatic species. Hückel’s rule also extends to aromatic charged systems, such as the cyclopentadienyl anion, cycloheptatrienyl cation, and cyclooctatetraene dianion.

7. The most important reaction of benzene is electrophilic aromatic substitution. The rate-determining step is addition by the electrophile to give a delocalized hexadienyl cation in which the aromatic character of the original benzene ring has been lost. Fast deprotonation restores the aromaticity of the (now substituted) benzene ring. Exothermic substitution is preferred over endothermic addition. The reaction can lead to halo- and nitrobenzenes, benzenesulfonic acids, and alkylated and acylated derivatives. When necessary, Lewis acid (chlorination, bromination, Friedel-Crafts reaction) or mineral acid (nitration, sulfonation) catalysts are applied. These enhance the electrophilic power of the reagents or generate strong, positively charged electrophiles.

8. Sulfonation of benzene is a reversible process. The sulfonic acid group is removed by heating 

with dilute aqueous acid.

9. Benzenesulfonic acids are precursors of benzenesulfonyl chlorides. The chlorides react with alco-hols to form sulfonic esters containing useful leaving groups and with amines to give sulfonamides, some of which are medicinally important.

10. In contrast with other electrophilic substitutions, including Friedel-Crafts acylations, Friedel-Crafts alkylations activate the aromatic ring to further electrophilic substitution, leading to product mixtures.

From "Organic Chemistry" Textbook of VOLLHARDT & SCHORE