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Chapter 6 and

Chapter 6 Amines and Amides

Chapter Objectives: • Learn to recognize the and functional groups. • Learn the IUPAC system for naming amines and amides. • Learn the important physical properties of the amines and amides. • Learn the major chemical reactions of amines and amides, and learn how to predict the products of amide synthesis and reactions. • Learn some of the important properties of condensation , especially the .

Mr. Kevin A. Boudreaux Angelo State University CHEM 2353 Fundamentals of Organic Organic and for Today (Seager & Slabaugh) www.angelo.edu/faculty/kboudrea

Nitrogen-Containing Functional Groups • is in Group V of the periodic table, and in most of its compounds, it has three single bonds and one : N

• In this chapter, we will take a look at two functional groups which contain nitrogen connected to : the amines and the amides. O

RR''N RCN R'

R' R" Amine Amide 2 Chapter 6 Amines and Amides

Classification and Nomenclature of Amines

3

Amines • Amines and amides are abundant in nature. They are a major component of and , nucleic , , etc. ( are N- containing, weakly basic organic compounds; thousands of these substances are known.)

• Amines are organic derivatives of , NH3, in which one or more of the three H’s is replaced by a group. • Amines are classified as primary (1°), (2°), or (3°), depending on how many carbon groups are connected to the nitrogen .

HHN RHN RHN RR''N

H H R' R' Ammonia 1° Amine 2° Amine 3° Amine 4 Chapter 6 Amines and Amides

Examples: Classifying Amines • Classify the following amines as primary (1°), secondary (2°), or tertiary (3°).

H CH3 NH2

CH3CH2CH2 N H CH3 N CH3 CH3CH2CHCH3

H N CH3CH2 N CH3 N H

5

Nomenclature of Amines • Simple 1°, 2°, and 3° amines: common (trivial) names are obtained by alphabetically arranging the names of the on the nitrogen and adding the suffix -amine (e.g., ethylmethylamine). • Amines in the IUPAC system: the “e” ending of the name for the longest chain is replaced with –amine. The amine group is located by the position number. Groups that are attached to the nitrogen atom are located using “N” as the position number. More complex primary amines are named with —NH2 as the amino . • Aromatic amines: named as derivatives of the NH2 parent compound . Substituents attached to the nitrogen are indicated by using “N-” as the location number.

aniline 6 Chapter 6 Amines and Amides

Examples: Nomenclature of Amines • Provide common names for the following 2° and 3° amines; for 1° amines, provide common and/or IUPAC names where possible.

H

CH3 NH2 CH3 NCH3

H

CH3 NCH2CH3 CH3CH2CH2 NH2

7

Examples: Nomenclature of Amines • Provide common names for the following 2° and 3° amines; for 1° amines, provide common and/or IUPAC names where possible.

NH2 CH3

CH3CH2CH2CHCH3 CH3 NCH3

NH CH 3 CH3CHCH2CH2 NH2 CH CH CH CHCH 3 2 2 3 NH2

8 Chapter 6 Amines and Amides

Examples: Nomenclature of Amines • Provide common names for the following 2° and 3° amines; for 1° amines, provide common and/or IUPAC names where possible.

OH

ONH2 NH2

CH3CCH2CH2CH2CHCH3

9

Examples: Nomenclature of Amines • Provide names for the following aromatic amines.

NH CH3 NH2

CH3

CH3 CH3 CH3 CH2CH3 N N

10 Chapter 6 Amines and Amides

Examples: Nomenclature of Amines • Provide names for the following aromatic amines.

CH3 CH3 CH3 H N N

CH3 CH2CH3

CH3 CH3 N

CH3CH2 CH3 11

Examples: Nomenclature of Amines • Draw structural formulas for the following molecules: – ethylisopropylamine

– tert-butylamine

– 2-pentanamine

12 Chapter 6 Amines and Amides

Examples: Nomenclature of Amines • Draw structural formulas for the following molecules: – N-methyl-2-propanamine

– 1,6-diaminohexane

– 3-amino-1-propanol

13

Examples: Nomenclature of Amines • Draw structural formulas for the following molecules: – N-methyl-2-chloroaniline

– N,3-diethylaniline

– N,N-

14 Chapter 6 Amines and Amides

Physical Properties of Amines

15

Physical Properties of Amines: H-Bonding • 1° and 2° amines can bond to each other:

CH3 N H CH3 N CH3

H H H H

CH3 N H N H CH3 N H N CH3

H CH3 CH3 CH3 • 3° amines cannot to each other:

CH3 NCH3

CH3 CH3 X CH3 N CH3X N CH3

16 CH3 CH3 Chapter 6 Amines and Amides

Physical Properties of Amines: Boiling Points • Nitrogen is less electronegative than , so the N—H bond is not quite as polar as the O—H bond. – Hydrogen bonds from N—H’s are not as strong as those resulting from O—H’s. – Hydrogen bonding between 1° and 2° amines is not as strong as those found in or carboxylic acids. • 1° and 2° amines have lower boiling points than alcohols of similar molecular weight. • 3° amines, since they do not hydrogen bond to each other, have boiling points similar to of the same molecular weight.

17

Physical Properties of Amines: Boiling Points : Carboxylic Alcohols 1°/2° Amines 3° Amines/

Molecular Boiling Name weight point 60.0 g/mol 118°C 1-propanol 60.1 g/mol 97°C propyl amine 59.1 g/mol 48°C ethylmethylamine 59.1 g/mol 36°C 59.1 g/mol 2.9°C 58.1 g/mol -0.5°C 18 Chapter 6 Amines and Amides

Physical Properties of Amines: • 1°, 2°, and 3° amines can all form hydrogen bonds with water. • Low-molecular weight amines are generally water- soluble.

H H H O O O

H H H H H

CH3 N H O CH3 N H O CH3 N CH3 H H H CH3 CH3

O HH

19

Physical Properties of Amines: • Low molecular-weight amines tend to have sharp, penetrating similar to ammonia • Higher molecular-weight amines often smell like rotting fish, and are often found in decaying animal tissues. NH2 NH2

CH3 N CH3 CH2CH2CH2CH2 CH2CH2CH2CH2CH2

CH3 NH2 NH2 Trimethylamine 1,4-Diaminobutane 1,5-Diaminopentane Responsible for the () (Cadaverine) odor of rotting fish A poisonous oil present in A poisonous, viscous liquid rotting flesh; produced present in rotting flesh; during the decomposition of produced during the the ; also decomposition of the amino partially responsible for the acid ; also partially odor of and responsible for the odor of urine and bad breath 20 Chapter 6 Amines and Amides

Examples: Predicting Physical Properties • Arrange the following compounds in order of increasing boiling point. (All of the compounds have about the same molecular weight.) propanoic acid, , 1-, ethyldimethylamine

21

Examples: Predicting Physical Properties • Which member of each of the following pairs of compounds would you expect to have a higher boiling point? – 2-aminopropane or 2-aminohexane

– or 1-aminohexane

– propanoic acid or diethylamine

– 1-pentanol or 1-aminopentane

22 Chapter 6 Amines and Amides

Some Important Alkaloids

23

Important Alkaloids

O O CH3 CH3 H CH 3 N H N N N N CH N 3 O N O N N N Nicotene CH 3 CH3 Found in tobacco plants; mild in small doses; Found in the seeds of Coffea arabica, Found in the seeds of addictive, but not especially roasted beans; inhibits the action of Theobroma cacao; the harmful itself phosphodiesterase, an which stimulating ingredient in inhibits cyclic . (AMP), which is responsible for forming in the bloodstream CH3 N HO N

CH3O

N Quinine CH3O 24 Ingredient in cough suppressants. Antimalarial from cinchona tree Chapter 6 Amines and Amides

CH3 CH3 CH3 N O N N

OCH 3 O H

H H H O O O O O O OH

OH The form which is “snorted” relaxes muscles and reduces secretion is the hydrochloride ; the of saliva during surgery; used to free- “crack” form is dilate pupils for eye examinations. used in treatment of motion burned and inhaled, and sickness reaches the brain in 15 H CCH seconds. 3 3 N+ R N Zephiran chloride H H () Antiseptic compound that kills bacteria and fungi on contact Poison from hemlock 25

O O CH2CH3 H N

N CH2CH3 CH3O H N CH3 N H H A naturally occuring hormone produced in the pineal gland; its production is triggered by the N absence of light; causes drowsiness in humans H diethylamide (LSD) at night, triggers to migrate, and signals A synthetic from alkaloids obtained to shed their winter coats; sold as a from , a which grows on rye treatment for jet lag. OH

Strychnine N N N H A poison from strychnos O plant (Nux vomica); used N as a rat and mouse poison HO P N H H O N OH H OH OH O O H Inosine Monophosphate (IMP) With monosodium glutamate (MSG), one of the major substances responsible for the of 26 Chapter 6 Amines and Amides

HO CH3O CH3 O

O

O O O N N N O CH3 CH3 CH3

HO HO CH3 O Found in the opium poppy; a Used in some cough syrups to More -soluble than morphine, CNS depressant; very effective depress the action of the cough and must be injected directly into painkiller center of the brain the bloodstream, but crosses the -brain barrier more readily, causing it to be more potent than morphine

27

Nitrogen Wastes The disposal of waste nitrogen from the body is a problem which different species of animals have solved in different ways: O H O H OH O NH2 O H N N NH2 N O O O N N NH2 N N O N O N H H H H H H Allantoic acid Marine vertebrates further Most contain enzymes metabolyze allantoin into Birds, and insects excrete nigrogen which metabolyze uric acid into wastes in the form of uric acid. Uric acid can allantoic acid. allantoin. be eliminated directly in the solid form, without being dissolved in water. It is produced in the O body from foods and beverages rich in , such as claret and port. inhibits the H H + – removal of salts of uric acid in the urine; these NN NH4 X salts instead deposit in the joints, causing gout. Marine excrete Dalmations have been bred to have black spots H H salts. with no white hairs in them on their coats; however, the gene which determines the Urea is the major organic presence of white hairs is linked to the gene component of urine; about 25 g which codes the enzyme which breaks down are excreted every day by uric acid into allantoin. Dalmations thus humans. Cartilaginous fish and also excrete urea. excrete uric acid instead of allantoin, and are 28 very susceptible to gout. Chapter 6 Amines and Amides

Antihistamines

NH2

NN H People who are allergic to pollen produce histamine, which causes blood vessels to dilate and leak, releasing fluid into surrounding tissues, causing watery eyes, sniffles, congestion, and other symptoms of hay fever (allergic rhinitis); also causes the symptoms of the common cold and swelling after insect bites.

CH3 N O CH3 CH3

CH3 N

OH H Diphenylhydramine / an ; active ingredient in Benadryl; found in the Chinese ma-huang plant; a sometimes used in sleeping pills decongestant used in many cold remedies

29

Antihistamines

O Cl

HO N OH

N N OH

Fexofenadine (Allegra®) O O A non-drowsy antihistamine; available by Loratadine (Claritin®) perscription only A non-drowsy antihistamine

N

N OH Cl O Cetrizide (Zyrtec®) A stronger antihistamine than Allegra or O Claritin, but causes drowsiness in some people 30 Chapter 6 Amines and Amides

Reactions of Amines

31

Bases •A base takes a proton (H+) from another species. A base produces , OH–, when dissolved in water: + – B + H2O  BH + OH •A strong base is one that completely dissociates in water (i.e., every molecule of the acid splits apart). •A weak base is one in which only a small percentage of the molecules are dissociated at any one time.

+ - • Acidic : pH < 7.00 ([H3O ] > [OH ]) + - • Basic solution: pH > 7.00 ([H3O ] < [OH ]) + - • Neutral solution: pH = 7.00 ([H3O ] = [OH ]) 32 Chapter 6 Amines and Amides

Chemical Properties of Amines: Basicity • Amines are weak organic bases. They react with water to produce alkylammonium ions and hydroxide anions: H H

R N ++H O R N H OH

H H H

• and with acids to produce alkylammonium salts:

H H

R N + HNCl R HCl

H H 33

Alkylammonium Salts • Salts of amines are named by changing “amine” to “ammonium” and adding the name of the negative to the end of the word:

H C2H3O2

CH3 NH3 Cl CH3 NCH2CH3 methylammonium chloride H ethylmethylammonium

CH2CH3

CH3CH2 NCH2CH3

H Br triethylammonium bromide 34 Chapter 6 Amines and Amides

Alkylammonium Salts • Salts of amines are generally white crystalline solids with high melting points. • The ionic charges makes these salts more soluble in water than the neutral amines. Many amine- containing drugs are administered in the form of alkylammonium salts to increase their solubility in bodily fluids. H3C H3C H - N HSO4 N

+ H2SO4

O O HO OH HO OH Morphine Morphine 35 water-insoluble water-soluble

Chemical Properties of Amines: Basicity • Ammonium salts may be converted back into neutral amines by a strong base:

+ - R—NH3 Cl + NaOH  R—NH2 + H2O + NaCl

• Thus, by adjusting the pH of the solution, it is possible to influence whether an amine is present in the neutral form or as its ammonium cation form:

acid (low pH) + - RNH2 + H2O RNH3 + OH base amine alkylammonium (high pH) ion

36 Chapter 6 Amines and Amides

Quaternary Ammonium Salts • In addition to salts of 1°, 2°, and 3° amines, it is possible to have amine cations which contain four alkyl groups attached to a nitrogen atom, which will always carry a positive charge, regardless of the pH of the surrounding solution. These are known as quaternary ammonium salts.

R''' CH2CH3

+ - + - RR''N X CH3 N CH2CH3 Cl

R' CH2CH3 quaternary triethylmethylammonium chloride ammonium salt • These salts are present in many antiseptics and antibacterial agents. 37

Examples: Basicity of Amines • Complete the following reactions:

CH3NH2 + HCl

NHCH3

+ HCl

CH 3 Cl

CH3 N H + NaOH

CH3 38 Chapter 6 Amines and Amides

Amides

39

Amides • Amides contain a nitrogen which is directly attached to a carbon in a :

O amide linkage ( bond)

RCN R'

R" Amide

O O O

RCN H RCN CH3 RCN CH3

H H CH3 N,N-unsubstituted amide N-substituted amide N,N-disubstituted amide 40 Chapter 6 Amines and Amides

Nomenclature of Amides • Amides are named by changing the -oic acid ending of the corresponding to -amide. If alkyl groups are attached to the nitrogen, they are named as N-alkyl substituents. O O O HCOH HCNH2 methanoic acid methanamide C () () NH2

O O

benzamide CH3 COHCH3 CNH2 ethanoic acid ethanamide (acetic acid) ()

41

Examples: Nomenclature of Amides • Name the following compounds: O O

CH3 CN CH3 CH3 N C CH3

H CH3

O CH3

CH3 N C CCH3

CH3 CH3

42 Chapter 6 Amines and Amides

Examples: Nomenclature of Amides • Name the following compounds:

OCH3

CH3CH2CH2 CNCH2CH3

NH2 O

CH3CH2CH2CHCH C N CH3

CH3 H

43

Examples: Nomenclature of Amides • Name the following compounds:

CH2CH3 OCH3

CH3CH2CH2CHCH2 CNCH2CH3

CH3

CH3 OCHCH2CH3 2CHCH3

CH3 N C CHCH2CH2CCH3

CH3 44 Chapter 6 Amines and Amides

Examples: Nomenclature of Amides • Name the following compounds:

O

C CH3 N

H

O

C N CH3

CH3

45

Examples: Nomenclature of Amides • Name the following compounds:

O

CH3 C N CH3 H

O

CH3 C N CH3

CH3

CH3 46 Chapter 6 Amines and Amides

Examples: Nomenclature of Amides • Draw structural formulas for the following molecules: – 2-methylpropanamide

– N,2,4-trimethylpentanamide

– N-ethyl-N-methylacetamide

47

Examples: Nomenclature of Amides • Draw structural formulas for the following molecules: – N,2-diethylbenzamide

– N,N,2,3,4-pentamethylbenzamide

– N,N,4,4-tetramethylbutanamide (what’s wrong with this name?)

48 Chapter 6 Amines and Amides

Physical Properties of Amides

49

Physical Properties of Amides • N,N-unsubstituted amides can form a complex network of hydrogen bonds. They tend to have high melting points and also high boiling points. O

RCN H

H H

O NH

RCN H O C

H R

O

RCNH 50 H Chapter 6 Amines and Amides

Physical Properties of Amides • N-substituted amides often have lower melting points and boiling points than N,N-unsubstituted amides because fewer hydrogen bonds can form. • N,N-disubstituted amides cannot form hydrogen bonds, and have even lower melting points and boiling points. • All amides can hydrogen bond with water, so low- molecular weight amides are water-soluble.

Boiling Point: N,N-unsubstituted amides N-substituted amides N,N-disubstituted amides

51

Examples: Predicting Physical Properties • Arrange the following compounds in order of increasing boiling point. (All of the compounds have about the same molecular weight.) N-ethylethanamide butanamide N,N-dimethylethanamide

52 Chapter 6 Amines and Amides

Important Amides

53

Important Amides

H O O N N

CH2CH3 Cl N O ON OON CH2CH3 H Thalidomide Until 1956, a very popular, safe sedative; the largest market was for (Valium) CH 3 pregnant women who were A benzodiazepene experiencing morning sickness. tranquilizer; acts by N,N-Diethyl-m-toluamide However, it caused massive birth enhancing the inhibitory Active ingredient in OFF defects in women who used it in the GABA; early states of pregnancy, and was since it binds to the same banned in Europe; it was never as , authorized for sale in the U.S. combinations of valium and ethanol can be deadly

54 Chapter 6 Amines and Amides

Hot Stuff

O NCS

CH O 3 Allyl N Capsaicin Used in horseradish flavor, H Found in red and green chili mustard oil, pickles, salad HO peppers; active component of dressings and sauces; mustard paprika plasters, medications and fumigants

O O O Component of white and CH3O black pepper N HO Zingerone The pungent, hot component of ginger O

55

Barbiturates

O H O H N N O S N N O H O H First synthesized by Adolf von Baeyer in 1864; Thiopental (Pentothal) are soporifics, and are used as An intravenous anesthetic tranquilizers and anesthetics; many are also addictive, and overdoses can be fatal. (Other barbiturates include Seconal, Veronal, Phenobarbitol, Thiopental, Amobarbitol, etc.)

O H O H N N O O N N O H O H (Amytal) Phenobarbitol Used in the treatment of insomnia Anti-seizure medication, sedative 56 Chapter 6 Amines and Amides

Sulfa Drugs

N O O

N SNH2 H2N SNH2

NH2 O O Prontosil Sulfanilamide OOH O

OH O N

H H O OH O N

H N Folic acid H N N 2 para-Aminobenzoic aid (PABA) H2N N N

Sulfanilamide, the first antibiotic, was discovered by Gerhard Damagk (Nobel Prize, 1939), who observed the antibacterial action of the red Protonsil; further researched showed that it was the metabolic byproduct, sulfanilamide, which was the active form. It prevents bacteria from synthesizing folic acid, which they need in order to grow. Bacterial enzymes synthesize folic acid using para-aminobenzoic acid (PABA); sulfanilamide fits into the enzyme more tightly, blocking it from taking up PABA, and thus blocking folic acid synthesis. The bacterium cannot grow, and eventually dies. Humans obtain folic acid from their diet (an essential ), so sulfa drugs do not harm people in this way (although they can cause allergic reactions). 57

Penicillin

R=

H G O N S CH3 R O Penicillin V N CH3 O CO2H Penicillin

NH2 OCH Penicillin is an antibiotic compound produced by 3 the molds Penicillium notatum and Penicillium chrysogenum; it was discovered by Alexander Fleming in 1928 in a culture of bread mold. There Methicillin are several varieties: Penicillin G and Methicillin are administered by injection; Penicillin V is an oral form which is not broken down in the OCH3 ; Ampicillin is a broad spectrum penicillin which can be administered by injection or orally 58 Chapter 6 Amines and Amides

Molecules To Dye For • are compounds that can be used to color other materials, such as clothing, paper, hair, etc. • Many organic dyes contain a long series of double bonds that are close together. If the chain of double bonds is long enough, these molecules can absorb low-energy light in the visible region of the electromagnetic spectrum, resulting in colors that are visible to the human eye.

O H O H

N N Br

N Br N HO HO Indigo Tyrian purple A naturally occurring blue dye which has been 6,6'-dibromoindigo used for thousands of years. It is obtained Tyrian purple, or “royal purple,” is a purple dye from an Indian plant (Indigofera tinctoria) and originally obtained from a species of mollusk (Murex) the European woad (Isatis tinctoria). Today, found near the cities of Tyre and Sidon in ancient indigo can be made synthetically, and is used Phoenicia. It took about 9,000 mollusk shells to in dyeing denim to make blue jeans. obtain one gram of the dye, making it very expensive. This dye was used by royalty (hence the name “royal purple”) and the Roman aristocracy. 59

Molecules To Dye For

CH3 NCH3

H N N NH2 2_ SO4

CH3 2 Mauve This is the first of the synthetic dyes. It was discovered by the 18-year-old English chemist William Henry Perkin in his home laboratory, while attempting to synthesize quinine (the only known treatment for malaria at that time). While cleaning up the sludge from one of his failed attempts, he noticed that the sludge was turning the water in his sink violet, and that cloth would pick up this purple color. Perkin patented his serendipitous discovery, and went into business making dyes, becoming so successful that he was able to retire at the age of 36 to focus his attention on chemical research.

60 Chapter 6 Amines and Amides

FD&C Dyes These color additives are approved by the Food and Drug Administration (FDA) under the Federal Food, Drug, and Cosmetic Act (FD&C, 1938, amended 1997) for use in foods. O H

NaO3S N - SO3 N SO3Na HO FD&C Blue No. 2 NaO3S SO3Na N N Indigo Carmine, Indigotine

FD&C Blue No. 1 Brilliant Blue FCF II OH NaO O O

I I - SO3 CO2Na

NaO3S SO3Na N N FD&C Red No. 3 Erythrosine FD&C Green No. 3 Fast Green FCF 61

FD&C Dyes

NaO3S NaO3S

CH3 OCH3

NN NN SO3Na SO3Na HO HO

FD&C Red No. 40 CO2Na Allura Red AC FD&C Yellow No. 6 N Sunset Yellow FCF N N NaO3SN HO FD&C Yellow No. 5 SO Na Tartrazine 3

CO2CH2CH3 CH3 OCH3

N N NN N NaO3S N HO HO

Orange B SO3Na Used in sausage and Citrus Red No. 2 frankfurter casings Used to color 62 Chapter 6 Amines and Amides

Molecules To Dye For

CH3 N N

CH3 NSO3Na Methyl orange N

NNO2 OH OH Para red CH3 O CH N N 3 N N CH3 N Methyl red CH3 N yellow

OH HO

N N N N

HO3S NH2 H2N SO3H

CH3O Chicago blue OCH3

SO3H HO3S 63

Molecules To Dye For O H3C CH3 N N

HO O O Resazurin

N Cl CH CH Cl 3 3 H3C CH3 N S N N N CH Blue CH 10B 3 3 CH3 (crystal violet) CH3

NH2 H2N

N N N N O O S S O O NaO Congo red ONa 64 Chapter 6 Amines and Amides

Reactions of Amides

65

Amide Formation • Amides are formed when acid chlorides react with 1° or 2° amines; 3° amines cannot form amides: OOHH

RCCl + R' N H RCNR'+ HCl

OOR'' R''

RCCl + R' N H RCNR'+ HCl

O R''

RCCl+ R'N R''' no reaction 66 Chapter 6 Amines and Amides

Amide Formation • Amides are also formed when acid anhydrides react with 1° or 2° amines.

O O HHO O

RCOCR+ R' N H RCNR'+ HO C R

O O R''O R'' O

RCOCR+ R' N H RCNR'+ HO C R

O O R''

RCOCR+ R'N R''' no reaction

67

Examples: Formation of Amides • Complete the following reactions:

O CH3

CCl+ CH3 NH

68 Chapter 6 Amines and Amides

Examples: Formation of Amides • Complete the following reactions:

O O

CH3 CO C CH3 + CH3CH2CH2NH2

69

Examples: Formation of Amides • Complete the following reactions:

O CH3

CH3 CCl+ CH3 NCH3

70 Chapter 6 Amines and Amides

Chemical Properties of Amides • Unlike amines, amides are not basic. • Amide hydrolysis can take place under acidic or basic conditions:

O R'' O R''

+ - RCNR'++H2O HCl RCOH + H N R' Cl

H

O R''O R''

RCNR'++NaOH RCO- Na+ H NR'

71

Examples: Reactions of Amines and Amides • Complete the following reactions:

O H

CH3 C NCH3 ++HClH2O

O H

CH3 C NCH3 + NaOH

72 Chapter 6 Amines and Amides

Condensation Polymers: Polyamides

73

Condensation Polymers: Polyamides O O H N(CH) NH H N(CH) NH 2 2 6 2 C (CH2)10 C 2 2 6 2 1,6-diaminohexane Cl sebacoyl chloride Cl 1,6-diaminohexane

O O

C (CH2)10 C

H2N(CH2)6 N N(CH2)6 NH2 H H

O O O O O O

C (CH2)10 C C (CH2)10 C C (CH2)10 C

Cl N (CH2)6 N N(CH2)6 N Cl H H H H

O O O O O O

C (CH2)10 C C (CH2)10 C C (CH2)10 C

H2N(CH2)6 N N (CH2)6 N N(CH2)6 N N(CH2)6 NH2 H H H H H H

O O O O O O O O O O

C (CH2)10 C C (CH2)10 C C (CH2)10 C C (CH2)10 C C (CH2)10 C

Cl N (CH2)6 N N (CH2)6 N N(CH2)6 N N(CH2)6 N Cl H H HHH H H H

74 etc. Chapter 6 Amines and Amides

Condensation Polymers: Polyamides O O

C (CH2)10 C

Cl NH—(CH2)6—HN H n -6,12 a Discovered by Wallace Carrothers at DuPont in 1934; polymers average about 10,000 g/mol; 3 billion pound of Nylon made per year; 60% used for nylon fiber in home furnishings (carpet); also used in textile fibers, tire cord, rope, parachutes, brushes, Velcro, electrical parts, medical applications (sutures, etc.) O O O O

C NNCC NNC

HHH H O O O O

C NNCC NNC

HHH H O O O O

C NNCC NNC 75 HHH H

Polyamides

NH2 O

H H2N N + O O O N Cl H Cl used in bullet-proof vests and tire cords O (an , "aromatic polyamide") O

76 Chapter 6 Amines and Amides

Polyamides

H2N NH2

O O O O

+ O O N N H H Cl Cl Nomex Insulates ceramic tiles on the space shuttle; used in firefighting equipment, race car driver suits, flight suits, the airbags on the Mars Pathfinder, Spirit, and Opportunity rovers (less strong than Kevlar, but has excellent thermal, chemical, and radiation resistance)

77

Polyurethanes

RNCO RNCO O HOR H OR C Isocyanate + A Urethane N

OH

H3CNCO HO OH

Toluene diisocyanate

OH

O OH O C

HN OH

O OH H C H C 3 N O 78 A Chapter 6 Amines and Amides

Neurotransmitters

79

Neurotransmitters • Neurotransmitters are small molecules that carry nerve impulses from one neuron to the next. • Neurons consist of the main cell body (the soma), long stemlike projections (the axons), and short fibers connected to the soma (the dendrites). • Neurons are not connected directly to each other, but are separated by a small gap called a synapse. • When an electrical current originating in a neuron reaches the synaptic terminals at the end of the axon, the terminals release neurotransmitter molecules into the synapse; these molecules diffuse across the synapse and bind to receptors on the dendrites of the next neuron, stimulating an electrical current, which travels along that neuron until it reaches the next synapse, and so on until the nerve impulse reaches the brain. 80 Chapter 6 Amines and Amides

Figure 6.5 A nerve cell and the transmission of a nerve signal.

81

HO

HO HO NH2

CO2H Dopa HO NH Synthesized from the amino acid tyrosine; used as a 2 treatment for Parkinson's disease, which is caused by a breakdown of dopamine-based neurons that control the Synthesized from dopa; used as a brain's motor system (dopamine cannot be administered treatment for low directly because it does not cross the blood-brain barrier; however, the L-form of dopa does)

HO

NH2

HO NH2 N OH H (NE) Synthesized from dopamine; an excess of NE in the Synthesized from the amino acid ; brain is related to feelings of elation or manic states; influences sleeping, body temperature, and low NE levels are linked to depression; the stimulant sensory perception; drugs that mimic serotonin action of epinephrine and NE in some cells can be are used to treat depression, anxiety, and reduced by beta blockers, which are used to treat obsessive-compulsive disorder; serotonin cardiac arrhythmias, angina, and hypertension blockers are used to treat migraine headaches and nausea resulting from 82 Chapter 6 Amines and Amides

HO

CH3 HO N

OH H Epinephrine (Adrenalin) More important as a hormone than a neurotransmitter; synthesized in the adrenal glad; release of adrenalin into the bloodstream in response to pain, anger, or fear increases blood glucose levels, and provides a sudden burst of energy (fight-or-flight response); increases force of heart contractions (raising blood pressure); also a vasoconstrictor; used in local anesthetics to keep the anesthetic from being washed away

O O CH 3 CH3 + H2N N OH O CH3 Gamma-aminobutanoic acid (GABA) A inhibitory neurotransmitter

83

Pheynlephrines and

CH3 CH3 CH3

CH3 CH3 NH2 N N

Amphetamine (Benzedrine) H OH H a powerful nervous stimulant; raises N-Methylamphetamine blood glucose levels, increases heart (Methedrine, "speed") Ephedrine / Pseudoephedrine rate and blood pressure Also a powerful nervous found in the Chinese ma-huang plant; a stimulant decongestant used in many cold remedies

O CH3

CH3 CH3 HO N O N CH3O OH H H CH3O 3,4-Methylenedioxymethamphetamine (MDMA), "Ectasy" Common decongestant

CH3O NH2 Hallucinogen from peyote cactus 84 Chapter 6 Amines and Amides

Amino Acids and Proteins

85

Amino Acids O H H2N OH

R Amino Acids

O O O O

H2N H2N H2N H2N OH OH OH OH (Gly) CH3 (Ala) (Val) (Leu)

O O H O O

H2N H2N N H2N OH OH OH OH

S (Pro) (Ile) (Met)

Phenylalanine (Phe) 86 Chapter 6 Amines and Amides

O O O O

H2N H2N H2N H2N OH OH OH OH

OH OH (Ser) (Thr)

OH N Tyrosine (Tyr) H Tryptophan (Try) O O O O

H2N H2N H2N H2N OH OH OH OH O NH2 SH NH NH (Cys) 2 (Gln) N O (His) (Asn) O O O O

H2N H2N H2N H2N OH OH OH OH O O NH2 OH N NH2 Lysine (Lys) OH H Glutamate (Glu) Arginine (Arg) O 87 Aspartate (Asp)

O

H2N O OH

H2N OH OH O O H O CH3 H2N O H2N N Alanine (Ala) Aspartate (Asp) OH Glycine (Gly) OH Glycine (Gly) CH3 Alanine (Ala)

O

H2N OH

O H O H2N H O N Glycine (Gly) N N OH H Tryptophan (Try) CH3 Alanine (Ala) OH

O Aspartate (Asp) 88 Chapter 6 Amines and Amides

O H O H2N H O N H O Glycine (Gly) N N CH3 OH Alanine (Ala) OH etc.

O Aspartate (Asp) N H Tryptophan (Try)

Gly Ala Asp Try a protein (a polyamide) Instructions for making proteins areencodedinDNA.

89

Three levels of structure in a telephone cord 90 Chapter 6 Amines and Amides

R-group interactions leading to a protein tertiary structure 91

Segment of a protein showing -helix, -pleated sheet,

and random coil structures 92 Chapter 6 Amines and Amides

Some Hideously Complex Molecules

93

O

OH O

O N(CH3)2 H OH O H Erythromycin an antibiotic O

OCH3 OH H H N NH CH3 OH 2 H2N N H N OH NH H NH O H O HO OH H H OH O O CHO Streptomycin OH OH an antibiotic CH3 94 Chapter 6 Amines and Amides

O

OO OH O

HN O O H N OH H O HO O H Taxol O O O NNH2 potential anti-cancer drug isolated from the O Pacific yew tree Bufotoxin O isolated from the toad Bufo OH marinus; increases the contractive power of weak O O N heart muscles; also causes H terrifying hallucinations

O

O OH O O 95

O H2N O

O CH3 NH2 CH3 O H2N H C NH 3 N N 2 H3C Co H NN CH3

CH3 O H2N O CH3 CH3 O NH2 Vitamin B12 (cobalamine) Found in meat, fish, eggs, and milk; a NH coenzyme involved in amino acid ; needed for the production O of red blood cells (a deficiency in N vitamin B12 results in anemia) H3CPO O OH O N CH3 O HO 96 CH3 Chapter 6 Amines and Amides

Functional Groups OH H H R R H CCH CC R CCR H H RR alkane aromatic ring (-ane) (-ene) (-yne) (phenyl-, -) (-phenol)

H H R

ROHC ROHC ROHC ROR R SH H R R (alkoxy-, -ether) primary (1°) alcohol secondary (2°) alcohol tertiary (3°) alcohol (-ol) (-ol) (-ol)

O O OH OR OH OR RHC RHC RRC RRC RCH R CR OR OR OR OR (-al) (-one) hemiketal ketal 97

O O O O O O

R COHRCO- M+ R COR RCCl RCOCR carboxylic acid salt acid chloride (-oic acid) (metal + -oate) (alkyl + -oate)

R

RHN RHN RRN RRN+

H R R R primary (1°) amine secondary (2°) amine tertiary (3°) amine quaternary ammonium salt (amino-, -amine) (-amine) (-amine) (alkyl ammonium + anion)

O O O O

RCNH2 RCNHR R C N R RO POH R OH amide ester (N-alkyl + -amide) 98 Chapter 6 Amines and Amides

Reactions of Amines and Amides 1. Reaction of an amine with water to produce an alkylammonium ion. H H

R N + H O R N H + -OH H H H amine alkylammonium ion

2. Reaction of an amine with acid to produce an alkylammonium salt. H H

R N + HNCl R H -Cl H H amine hydrochloric alkylammonium acid chloride

3. Conversion of an alkylammonium salt back to an amine. + - R—NH3 Cl + NaOH  R—NH2 + H2O + NaCl

99

4. Formation of an amide. (NR with tertiaryamines.) OORR

R' C Cl+ RH N R'CNR+ HCl acid chloride amine amide (1° or 2°) O OORRO

R' C OCR+ RH N R'CNR+ R' C OH acid anhydride amine amide carboxylic (1° or 2°) acid 5. Hydrolysis of amides under acidic and basic conditions. OOH + - R' C N R++H2O HCl R' C OH + H N R Cl carboxylic R acid R amide alkylammonium salt OO

R' C N R+ NaOH R' C O- Na+ + H N R carboxylate R salt R amide amine 100