Amines Chapter 16 Amines and Amides Derivatives of ammonia, NH 3, where one or more hydrogen atoms have been replaced by an aromatic or alkyl group (R) Classified on the basis of molecular structure Primary amines: Have one alkyl or aromatic group bonded to nitrogen R NH 2 Secondary amines: Have two alkyl or aromatic groups bonded to nitrogen R 2 NH Tertiary amines: Have three alkyl or aromatic groups bonded to nitrogen R 3 N Subclasses of Amines Classify benzyldimethylamine 1. 1 amine 2. 2 amine 3. 3 amine 4. 4 amine Common Naming for Amines Used extensively for amines with low molecular weight Steps Alphabetically link the names of the alkyl or aromatic groups bonded to the nitrogen Attach the suffix -amine so the name is one word Use di- or tri- prefixes for identical alkyl groups IUPAC Naming for Amines Determine the root name by the longest continuous chain of carbon atoms Change the -e ending in the alkane to amine Position of amino group on the chain is shown by a number Numbers are also used to locate other substituents on the carbon chain Italic capital N is used as a prefix for substituents on nitrogen 1
Naming Aromatic Amines Compounds are named as substituted anilines Simplest aromatic amines An italic N is used to indicate that an alkyl group is attached to the nitrogen and not to the ring Example You are not responsible for naming aromatic amines Physical Properties of Amines Simple, low molecular weight amines are gases at room temperature Heavier, more complex compounds are liquids or solids N H bond is not quite as polar as the O H bond Primary and secondary amines form hydrogen bonds, which are not as strong as those of alcohols since nitrogen is less electronegative than oxygen Boiling points are somewhat lower than those of alcohols with similar molecular weights Physical Properties of Amines Tertiary amines cannot form hydrogen bonds since nitrogen has no attached hydrogen atom Boiling points are similar to alkanes with similar molecular weights Amines with fewer than 6 carbon atoms are soluble in water Result of hydrogen bond formation between amine functional groups and water molecules Physical Properties of Amines (continued 2) Low molecular weight amines have a sharp, penetrating odor similar to that of ammonia Some larger amines have the odor reminiscent of decaying fish Some amines are partially responsible for the odor of decaying animal tissue - Putrescine and cadaverine Table 16.2 - Properties of Some Amines Which of the following has the strongest intermolecular forces? 1. Primary alcohols 2. Primary amines 3. Ethers 4. Thiols 2
Biologically Important Amines - Neurotransmitters Substance that acts as a chemical bridge in nerve impulse transmission between nerve cells Biologically Important Amines - Neurotransmitters Acetylcholine Involved in the transmission of neural impulses Dopamine Synthesized from the amino acid tyrosine Norepinephrine Synthesized from dopamine and may be associated with mental illness Serotonin Synthesized from the amino acid tryptophan Can be associated with mental illness Biologically Important Amines - Epinephrine Epinephrine (adrenaline) More important as a hormone than as a neurotransmitter Synthesized in the adrenal gland Acts to increase the blood level of glucose for a sudden burst of energy Released in response to pain, anger, or fear Called the fight-or-flight hormone Biologically Important Amines - Epinephrine Raises blood pressure by increasing the rate and force of heart contractions and constricting peripheral blood vessels Component in injectable local anesthetics because it constricts blood vessels in the vicinity of the injection Used to: Reduce hemorrhage Treat asthma attacks Combat anaphylactic shock Biologically Important Amines - Amphetamine Amphetamine (Benzedrine ) Powerful nervous system stimulant Similar in structure to epinephrine Raises blood glucose level and increases pulse rate and blood pressure Biologically Important Amines - Amphetamine Addictive and concentrate in the brain and nervous system Produce: Long periods of sleeplessness Weight loss Paranoia Prompt the use of other drugs to prevent the crash brought on by discontinuation of use Structural arrangement is referred to as phenethylamine 3
Biologically Important Amines - Alkaloids Alkaloids - Class of nitrogen-containing organic compounds obtained from plants Include nicotine, which is found in tobacco Acts as a stimulant in small doses and is not especially harmful Habit-forming Addiction exposes habitual tobacco users to other harmful substances (Tars, CO, and polycyclic carcinogens) Other Alkaloids - Caffeine Found in coffee, cola drinks, tea, chocolate, and cocoa Mild stimulant of the respiratory and central nervous systems Side effects include nervousness and insomnia Mild diuretic and is used in pain relievers, cold remedies, diet pills, and stay-awake pills Should be prudently consumed by pregnant women Can enter the bloodstream, cross the placental barrier, and reach the fetus Other Alkaloids - Opium Dried juice of the poppy plant Contains numerous alkaloids, including morphine and codeine Morphine exerts a soothing effect on the body, making it a useful painkiller Codeine in cough syrup helps depress the action of the cough center in the brain Highly addictive Morphine Derivative Heroin Destructive and a hard illegal drug Addicts are likely to commit crimes to support their habits Medically-Used Alkaloids Quinine Used to treat malaria Atropine Preoperative drug used to: Relax muscles Reduce the secretion of saliva in surgical patients Dilate the pupil of the eye in patients undergoing eye examinations Chemical Reactions Amines as Bases All amines behave as weak bases in water and produce OH ions All amines behave as weak bases and form salts when they react with acids such as HCl 4
Chemical Reactions Amines as Bases Amines react with other acids to form salts Sulfuric, nitric, phosphoric, and carboxylic acids Example Amine Salts Named by changing amine to ammonium and adding the name of the negative ion derived from the acid Have physical properties characteristic of ionic compounds White crystalline solids with high melting points More soluble in water than the parent amines Amine Salts Can be converted back to amines by adding a strong base Form in which amines occur in solutions is ph dependent, just as is the case for carboxylic acids In a solution of low ph (high H + ), salt form of amines predominates In a solution of high ph (high OH ), amine form is favored Amides Formed when amines react with acid chlorides or acid anhydrides Characteristic functional group is a carbonyl group attached to nitrogen Amide linkage: Carbonyl carbon nitrogen single bond of the amide group Amides (continued) Can be thought of as containing an ammonia or amine portion and a portion derived from a carboxylic acid Chemical Reaction Amine Esterification Primary and secondary amines can be used for preparation, but tertiary amines do not react to form amides General reactions Note - Reaction of an amine with a carboxylic acid normally produces a salt and not an amide 5
Chemical Reaction Amine Esterification Reaction Map for Amines Naming Amides Steps Use the carboxylic acid name Drop the -ic ending (common name) or -oic ending (IUPAC name) and change it to -amide Naming Amides (continued) If an alkyl group is attached to the nitrogen atom of the amides: Name of the alkyl group precedes the name of the amide Italic capital N is used to denote that the alkyl group is bonded to the nitrogen Which of the following is an amide? What is the IUPAC name of this molecule? 1. 2. 3. 4. 1. N,1-diethylmethanamide 2. N-ethylpropanamide 3. 3-N-4-hexanone 4. Ethyl N-propanoate 6
Physical Properties of Amides Formamide is the only unsubstituted amide that is a liquid at room temperature All other unsubstituted amides are solids at room temperature Complex hydrogen bonding between unsubstituted and monosubstituted amides causes them to have high melting points Hydrogen Bonding in Amides Amides with fewer than 6 carbon atoms are water soluble Trisubstituted amides have sufficiently fewer hydrogen bonds with water and are therefore much less soluble Physical Properties of Amides Classify the following amide: 1. Unsubstituted 2. Monosubstituted 3. Disubstituted 4. Trisubstituted Which of the following CANNOT experience hydrogen bonding with another molecule of the same type? 1. More than one of these answer choices is correct 2. 3. Chemical Reaction - Amide hydrolysis Amides are neither acidic nor basic Carbonyl group bonded to the nitrogen destroys the basicity of the original amine Nitrogen of the amine replaces the acidic OH of the carboxylic acid Amide hydrolysis Amide is cleaved to produce a carboxylic acid and an amine or ammonia 4. 7
Chemical Reaction - Amide hydrolysis Chemical Reaction - Amide hydrolysis Requires the presence of strong acid or base and heat Nature of final products depends on the reactants used One product must always be in the form of a salt Central reaction in the digestion of proteins and the breakdown of proteins within cells Hydrolysis is catalyzed by enzymes in the body Some Important Amides in Medicine Basic hydrolysis of amides will produce and 1. carboxylic acids and amines 2. carboxylate salts and amines 3. carboxylic acids and ammonium salts 4. carboxylate salts and ammonium salts Some Important Amides in Medicine Amides as Aspirin Substitutes Acetaminophen Good pain reliever Has no antiinflammatory effect Not a good substitute for aspirin Naproxen A.K.A. Aleve Longer lasting form of ibuprofen Ibuprofen Not really an amide. better antiinflammatory than aspirin 8