Chem 1152: Ch. 16 Amines

Nitrogen Mostly inert gas (N2) under standard conditions ~78% of atmosphere Found in: Ammonia (NH3) Nitrates (fertilizers) Nitric acid (HNO3) Propellants (N2O, nitrous oxide) Explosives (nitroglycerine) Cyanides (CN-) 4th most abundant element in human body Critical to building blocks of life/CNS function Proteins DNA RNA Neurotransmitters nitroglycerine Amino acid

Amines Organic derivatives of ammonia One or more H atoms replaced by aromatic or alkyl group Primary (1°) Secondary (2°) Tertiary (3°) : : : : ammonia R-OH alcohols Seager SL, Slabaugh MR, Chemistry for Today: General, Organic and Biochemistry, 7th Edition, 2011

Naming Amines – Common Names For low MW amines Alphabetically link names of alkyl or aromatic groups bonded to nitrogen, attach suffix –amine. methylamine ethylmethylamine trimethylamine methylphenylamine propylamine

Naming Amines – IUPAC Names Replace –e in alkane with –amine. Number position of amino group lowest on parent chain. If substituent on nitrogen, prefixed with N.

Naming Amines – IUPAC Names Replace –e in alkane with –amine. Number position of amino group lowest on parent chain. If substituent on nitrogen, prefixed with N. 3-Pentanamine 2-Hexanamine 3-Methyl-1-butanamine N-Methyl-2-butanamine N-Methyl-2-hexanamine N,N-Dimethyl-2-hexanamine N-Ethyl-N-methyl-2-hexanamine 2,5-hexanediamine cyclohexanamine

Naming Amines – Aromatics Usually named as substituted anilines For groups on N of aniline, identify with N to indicate not attached to ring aniline 2-Methylaniline 3-Ethylaniline N-Ethylaniline N-Ethyl-N-methylaniline N,N-dimethylaniline diphenylamine 2-Ethyl-N-methylaniline N-Ethyl-2-methylaniline 3-phenyl-2-heptanamine

Priority of Functional Groups in IUPAC Names 8 8

Physical Properties of Amines 1° and 2° amines form H-bonds among themselves (increases BP) Bonds weaker for amines than alcohols (EN of oxygen > nitrogen) BP’s of 1° and 2° amines lower than alcohols of comparable MW alcohol amine Amines with 6 or fewer C’s (1° > 2° > 3°) soluble in water due to H-bonding Amines stink! Low MW amines smell like ammonia Higher MW amines smell like rotten fish putrescine cadaverine

Chemical Properties of Amines Basicity: Amines are weak bases From Brønsted-Lowry Base accepts proton and becomes a conjugate acid

Chemical Reactions of Amines Amines reversibly react with water, form hydroxide ions Amines form salts when they react with acids

Amine Salts Naming: Change amine to ammonium and add name of negative ion derived from acid Ethyldimethylamine (common) N,N-dimethylethanamine (IUPAC) ethyldimethylammonium ethyldimethylammonium bromide Amine salts are white crystalline solids with high MP’s. Amine drugs usually given in form of salts to improve their ability to dissolve in body fluids Seager SL, Slabaugh MR, Chemistry for Today: General, Organic and Biochemistry, 7th Edition, 2011

Amine Salts Amine salts are pH dependent, like CA’s. (high pH) amine salt (low pH) Amine salts may have 4 alkyl/benzene groups  quaternary ammonium salts Acetylcholine is important QA salt involved in transmission of nerve impulses Some QA salts have antiseptic qualities that kill bacteria and fungi. e.g. benzalkonium (Zephiran) chloride used by physicians to scrub before surgery and to sterilize instruments Seager SL, Slabaugh MR, Chemistry for Today: General, Organic and Biochemistry, 7th Edition, 2011

Cocaine is sold illegally as an amine salt. is reacted with NaOH to produce the free amine form known as “crack.” 14 14

Amides Amides are combination of CA and ammonia or amine joined by amide linkage. Amide Ester Carboxylic Acid Carboxylic Acid Amide linkage Ammonia or amine Ester linkage Alcohol Not formed by reaction between CA and amine (produces salt)

Amines Form Amides Amides are formed through reaction of primary and secondary amines with acid chlorides and acid anhydrides. Similar to esterification reactions. Seager SL, Slabaugh MR, Chemistry for Today: General, Organic and Biochemistry, 7th Edition, 2011

Amide Reactions No Rxn

Synthesis of Nylon Carpeting Clothing Medical tubing Sutures Parachutes Seager SL, Slabaugh MR, Chemistry for Today: General, Organic and Biochemistry, 7th Edition, 2011

Alkaloids Weakly basic amines derived from plants Stimulate CNS/Resp. systems Treatment of malaria Opiates CNS Depressants, used as painkillers Morphine derivative Seager SL, Slabaugh MR, Chemistry for Today: General, Organic and Biochemistry, 7th Edition, 2011

Synthesizing Drugs: Pharmacology Alkaloids can be used as the basis for designing new drugs, such as procaine, lidocaine, and Demerol, that retain some of the characteristics of alkaloids. modify the structures of cocaine and morphine to produce anesthesia, but without the addictive side effects. 20 20

An Amide as an Aspirin Substitute Acetylsalicylic acid Aspirin Pain reliever Fever reducer Anti-inflammatory Acetaminophen Pain reliever Fever reducer Does not irritate intestinal tract Harmful side effects Allergic reactions Gastrointestinal bleeding Can induce Reye’s syndrome in children Negatives Not an anti-inflammatory Overuse can lead to liver and kidney damage Seager SL, Slabaugh MR, Chemistry for Today: General, Organic and Biochemistry, 7th Edition, 2011

Naming Amides Simple amides named after corresponding carboxylic acids by changing –ic or –oic of acid to –amide. Common names are used more often than IUPAC names. Common name formic acid formamide IUPAC name methanoic acid methanamide Common name acetic acid acetamide IUPAC name ethanoic acid ethanamide Common name benzoic acid benzamide IUPAC name benzoic acid benzamide

Naming Amides Simple amides named after corresponding carboxylic acids by changing –ic or –oic of acid to –amide. Common names are used more often than IUPAC names. Use italicized capital N to identify alkyl groups bonded to nitrogen. Common N-methylformamide N,N-dimethylacetamide N-ethyl-N-methylbenzamide IUPAC N-methylmethanamide N,N-dimethylethanamide N-ethyl-N-methylbenzamide

N,N-diethylethanamide N-isobutylbutanamide N-ethyl-N-phenylbenzamide Naming Amides Simple amides named after corresponding carboxylic acids by changing –ic or –oic of acid to –amide. Common names are used more often than IUPAC names. Use italicized capital N to identify alkyl groups bonded to nitrogen. N,N-diethylethanamide N-isobutylbutanamide N-ethyl-N-phenylbenzamide 2,N-dimethylbenzamide

Physical Properties of Amides Unsubstituted amides can form complex networks of intermolecular H-bonds Increases MP’s of these substances Increasing the number of substituents on amide reduces H-bonding Reduces MP’s and BP’s Amides do form H-bonds with water Increases solubility Seager SL, Slabaugh MR, Chemistry for Today: General, Organic and Biochemistry, 7th Edition, 2011

Amide Hydrolysis Most important rxn is hydrolysis May involve either acid or base One of the products will always be a salt Seager SL, Slabaugh MR, Chemistry for Today: General, Organic and Biochemistry, 7th Edition, 2011

Amide Hydrolysis Seager SL, Slabaugh MR, Chemistry for Today: General, Organic and Biochemistry, 7th Edition, 2011

methylammonium chloride Amide Hydrolysis acetamide Acetic acid Ammonium chloride N-methylacetamide Acetic acid methylammonium chloride N-methylacetamide Sodium acetate methylamine

Ethylammonium chloride Amide Hydrolysis N-ethylbenzamide Ethylammonium chloride Benzoic acid N-ethylbenzamide Ethylamine Sodium benzoate

Amines as Neurotransmitters Neurotransmitters: Molecules that carry chemical messages between neurons in nervous system released into synapse (gap between synaptic terminal of one neuron and Dendrite of another) in response to electrical signal Diffuse across synapse and bind to receptors on dendrites of next neuron In the CNS, the most important neurotransmitters are amines Seager SL, Slabaugh MR, Chemistry for Today: General, Organic and Biochemistry, 7th Edition, 2011

Amine Neurotransmitters: Acetylcholine Acetylcholine (ACh) was first identified neurotransmitter. Neurotransmitters communicate between CNS and muscle. When stimulated, it releases into the synapse where it binds to muscle cell receptors causing the muscles to contract. Acetylcholine is linked to Alzheimer’s disease In Alzheimer’s disease, acetylcholine levels may decrease by 90%. 31

Catecholamines Amines derived from the essential AA tyrosine (found in egg whites, turkey, soy) Include dopamine, norepinephrine, and epinephrine Closely related in structure, and have similar effects. 32

Norepinephrine and Epinephrine Norepinephrine and epinephrine (adrenaline), produced in adrenal glands, are hormonal neurotransmitters that play a role in sleep, attention and focus, and alertness. act as drugs related to fight or flight response directly increasing heart rate triggers the release of glucose from energy stores increases blood flow to skeletal muscle increases the brain's oxygen supply Excess norepinephrine (NE) results in feelings of elation Low NE levels may cause depression Seager SL, Slabaugh MR, Chemistry for Today: General, Organic and Biochemistry, 7th Edition, 2011

Dopamine Dopamine is produced in the nerve cells of the midbrain and acts as a natural stimulant to give us energy and feelings of enjoyment. Cocaine and amphetamine block the reuptake of dopamine resulting in a longer lifetime in synapse. 34

Amphetamines Amphetamines structurally and chemically similar to adrenaline Raise glucose level in blood Increase pulse rate Increase blood pressure May be legally prescribed to elevate mood or reduce fatigue Street names: Bennies, pep pills, Reds, red devils, speed, dexies, uppers Seager SL, Slabaugh MR, Chemistry for Today: General, Organic and Biochemistry, 7th Edition, 2011

Serotonin Serotonin helps us relax, sleep deeply and peacefully, think rationally, and it provides us a feeling of well-being and calmness. Serotonin is synthesized from the amino acid tryptophan. Low serotonin levels may be associated with depression, anxiety disorders, etc. Prozac and Paxil (antidepressant drugs) are selective serotonin reuptake inhibitors (SSRIs). 36

Histamine Synthesized in nerve cells in hypothalamus from AA histidine. Produced by immune system in response to pathogens and invaders, or injury. When histamine combines with histamine receptors, it produces allergic reactions. 37

AA Neurotransmitter Glutamate Most abundant neurotransmitter in the nervous system. Involved in cognitive functions (learning and memory). Used as a source of energy for certain types of brain tumors. Too much glutamate in the spinal cord causes degeneration of nerve cells (known as Lou Gehrig’s disease). Precursor for synthesis of GABA. GABA produces a calming effect by inhibiting the ability of nerve cells to send electrical signals to nearby nerve cells. 38