Download Compounds Containing A Single Bond To A

ORGANIC CHEMISTRY
Dr. Serkan SAYINER
[email protected]
Compounds Containing A
Single Bond To A Heteroatom
Alkyl Halides, Alcohols, Ethers, Amines, Thiols, Sulfides
Compounds Containing a Single Bond to a
Heteroatom
 Several types of functional groups contain a carbon
atom singly bonded to a heteroatom.
• These are alkyl halides, alcohols, ethers, amines, thiols and
sulfides.
 Molecules containing these functional groups may be
simple or very complex.
• It doesn’t matter what else is present in other parts of the
molecule.
Bromomethane
Methanol
Dimethyl ether
Methylamine
Methanethiol
Dimethyl sulfide
Alkyl Halides
Introduction, Nomeclature (IUPAC system and common names), Physical Properties, Interesting
Alkyl Halides, The Polar Carbon–Halogen Bond (substitution and elimination reactions)
Introduction
 Alkyl halides are organic molecules containing a
halogen atom X bonded to an sp3 hybridized carbon
atom.
• Halogens are any of the elements fluorine, chlorine, bromine,
iodine, and astatine, occupying group VIIA (17) of the periodic
table. They are reactive nonmetallic elements that form
strongly acidic compounds with hydrogen, from which simple
salts can be made.
• Denoting lamps and radiant heat sources use a filament
surrounded by the vapor of iodine or another halogen.
Introduction
 Alkyl halides are classified as primary (1°), secondary
(2°), or tertiary (3°) depending on the number of
carbons bonded to the carbon with the halogen.
• Whether an alkyl halide is 1°, 2°, or 3° is the most important
factor in determining the course of its chemical reactions.
• Alkyl halides have the general molecular formula CnH2n+1X, and
are formally derived from an alkane by replacing a hydrogen
atom with a halogen.
Introduction
 There are four types of organic halides having the
halogen atom in close proximity to a π bond.
1. Vinyl halides have a halogen atom bonded to a carbon–carbon
double bond
2. Aryl halides have a halogen atom bonded to a benzene ring.
3. Allylic halides have X bonded to the carbon atom adjacent to
a carbon–carbon double bond
4. Benzylic halides have X bonded to the carbon atom adjacent
to a benzene ring.
Nomenclature
 The systematic (IUPAC) method for naming alkyl halides
follows from the basic rules described in hydrocarbons.
 They have common names too, because many low molecular
weight alkyl halides are often referred to by their common
names.
 According to IUPAC System;
• An alkyl halide is named as an alkane with a halogen substituent—
that is, as a halo alkane. To name a halogen substituent, change
the -ine ending of the name of the halogen to the suffix –o (chlorine
→ chloro).
Name the parent chain as an alkane,
with the halogen as a substituent
bonded to the longest chain.
Begin at the end nearest the first
substituent, either alkyl or
halogen.
ANSWER: 2-chloro-5-methylheptane
Nomeclature
 Common Names
• Common names for alkyl halides are used only for simple alkyl
halides. To assign a common name:
• Name all the carbon atoms of the molecule as a single alkyl group.
• Name the halogen bonded to the alkyl group. To name the halogen,
change the -ine ending of the halogen name to the suffix -ide; for
example, bromine  bromide.
• Combine the names of the alkyl group and halide, separating the words
with a space.
Physical Properties
 Alkyl halides are weakly polar molecules.
 They exhibit dipole–dipole interactions because of their
polar C—X bond, but because the rest of the molecule
contains only C—C and C—H bonds they are incapable of
intermolecular hydrogen bonding.
 Alkyl halides have higher boiling points and melting
points than alkanes having the same number of carbons.
• CH3CH3 bp= -89º C iken CH3CH3Br bp= 39º C
Physical Properties
 Boiling points and melting points increase as the size of R
increases.
• Larger surface area, higher boiling and melting point.
 Boiling points and melting points increase as the size of X
increases.
• More polarizable halogen, higer melting and boiling point.
 RX is soluble in organic solvents, but not in water.
Interesting Alkyl Halides
 Many simple alkyl halides make excellent solvents because
they are not fl ammable and dissolve a wide variety of
organic compounds.
 Compounds in this category include CHCl3 (chloroform or
trichloromethane) and CCl4 (carbon tetrachloride or
tetrachloromethane).
 Large quantities of these solvents are produced industrially
each year, but like many chlorinated organic compounds,
both chloroform and carbon tetrachloride are toxic if inhaled
or ingested.
• Chloromethane (CH3Cl) is produced by giant kelp and algae and
also found in emissions from volcanoes such as Hawaii’s Kilauea.
• Dichloromethane (or methylene chloride, CH2Cl2) is an
important solvent, once used to decaffeinate coffee. Coffee is
now decaffeinated by using supercritical CO2 (liquid state) due
to concerns over the possible ill effects of trace amounts of
residual CH2Cl2 in the coffee.
• Halothane (CF3CHClBr) is a safe general anesthetic that has now
replaced other organic anesthetics such as CHCl3 (chloroform),
which causes liver and kidney damage, and CH3CH2OCH2CH3
(diethyl ether), which is very flammable.
Interesting Alkyl Halides
 Synthetic organic halides are also used in insulating
materials, plastic wrap, and coatings. Two such
compounds are Teflon and poly(vinyl chloride) (PVC).
Interesting Alkyl Halides
 Although the beneficial effects of many organic halides
are undisputed, certain synthetic chlorinated organics
such as the chlorofluorocarbons and the pesticide DDT
have caused lasting harm to the environment.
• Chlorofluorocarbons having been extensively used as a
refrigerant and an aerosol propellant.
• Sunlight catalyzes their decomposition, a process that
contributes to the destruction of the ozone layer.
Interesting Alkyl Halides
• DDT is an organic molecule with valuable short-term effects
that has caused long-term problems. DDT kills insects that
spread diseases such as malaria and typhus, and in controlling
insect populations, DDT has saved millions of lives worldwide.
• DDT is a weakly polar organic compound that persists in the
environment for years. Because DDT is soluble in organic
media, it accumulates in fatty tissues.
• DDT is acutely toxic to many types of marine life (crayfish, sea
shrimp, and some fish), but the long-term effect on humans is
not known.
The Polar Carbon–Halogen Bond
 The properties of alkyl halides dictate their reactivity.
 The electronegative halogen X creates a polar C– X bond,
making the carbon atom electron deficient. The chemistry
of alkyl halides is determined by this polar C—X bond.
 The characteristic reactions of alkyl halides are
substitution and elimination. Because alkyl halides contain
an electrophilic carbon, they react with electron-rich
reagents; Lewis bases (nucleophiles) and Brønsted–Lowry
bases.
The Polar Carbon–Halogen Bond
 A nucleophile is a reactant that provides a pair of
electrons to form a new covalent bond. In other
words, nucleophiles are Lewis bases.
 When the nucleophile donates a pair of electrons to a
proton, it’s called a Brønsted base, or simply, “base”.
• Nucleophiles and bases are structurally similar: both have a
lone pair or a π bond. They differ in what they attack.
• Bases attack protons. Nucleophiles attack other electron-
deficient atoms (usually carbons).
The Polar Carbon–Halogen Bond
 Alkyl halides undergo substitution reactions with
nucleophiles.
• In a substitution reaction of RX, the halogen X is replaced by
an electron-rich nucleophile :Nu–. The C—X σ bond is broken
and the C—Nu σ bond is formed.
The Polar Carbon–Halogen Bond
 Alkyl halides undergo elimination reactions with
Brønsted–Lowry bases.
• In an elimination reaction of RX, the elements of HX are
removed by a Brønsted–Lowry base :B.
The Polar Carbon–Halogen Bond
 All elimination reactions involve loss of elements from
the starting material to form a new π bond in the
product.
 Alkyl halides undergo elimination reactions with
Brønsted–Lowry bases. The elements of HX are lost and
an alkene is formed.
THE POLAR CARBON–HALOGEN BOND
Removal of the elements of HX, called dehydrohalogenation, is
one of the most common methods to introduce a π bond and
prepare an alkene.
Alcohols and Ethers
Introduction, Nomenclature, Physical Properties, Interesting Alcohols, Ethers, and Epoxides,
Preparation of Alcohols and Ethers, Reactions of Alcohols, Oxidation and Blood Alcohol
Screening, The Metabolism of Ethanol, Reactions of Ethers
Introduction
 Alcohols and ethers are two functional groups that
contain carbon–oxygen σ bonds.
• Although alcohols and ethers share many characteristics, each
functional group has its own distinct reactivity, making each
unique and different from the alkyl halides.
Introduction
 Alcohols (ROH) contain a hydroxy group (OH group)
bonded to an sp3 hybridized carbon atom.
 Alcohols are classified as primary (1°), secondary (2°), or
tertiary (3°) based on the number of carbon atoms bonded
to the carbon with the OH group.
 Compounds having a hydroxy group on an sp2 hybridized
carbon atom —enols and phenols— undergo different
reactions than alcohols.
• Enols have an OH group on a carbon of a C=C double bond.
• Phenols have an OH group on a benzene ring.
Introduction
 Ethers (ROR) have two alkyl groups bonded to an
oxygen atom.
 An ether is symmetrical if the two alkyl groups are the
same, and unsymmetrical if they are different.
Introduction
 Both alcohols and ethers are organic derivatives of H2O,
formed by replacing one or both of the hydrogens on the
oxygen atom by R groups, respectively.
 Epoxides are ethers having the oxygen atom in a
three-membered ring. Epoxides are also called
oxiranes.
Nomenclature
 To name an alcohol or ether using the IUPAC system, we
must learn how to name the functional group either as a
substituent or by using a suffix added to the parent
name.
 Naming Alcohols
• In the IUPAC system, alcohols are identified by the suffix -ol.
Change the -e ending of
the parent alkane to the
suffix -ol.
Step [2] Number the carbon chain to give the OH group the lower
number, and apply all other rules of nomenclature.
Answer: 5-methyl-3-hexanol
Nomenclature
 When an OH group is bonded to a ring, the ring is
numbered beginning with the OH group.
 Because the functional group is always at C1, the “1” is
usually omitted from the name.
 The ring is then numbered in a clockwise or
counterclockwise fashion to give the next substituent the
lower number.
Nomenclature
 Common names are often used for simple alcohols. To
assign a common name:
• Name all the carbon atoms of the molecule as a single alkyl
group.
• Add the word alcohol, separating the words with a space.
Nomenclature
 Compounds with two hydroxy groups are called diols
(using the IUPAC system) or glycols.
 Compounds with three hydroxy groups are called
triols, and so forth... Poliols.
 To name a diol, for example, the suffix -diol is added to
the name of the parent alkane, and numbers are used in
the prefix to indicate the location of the two OH groups.
Nomenclature
 Naming Ethers
• Simple ethers are usually assigned common names.
• To do so, name both alkyl groups bonded to the oxygen,
arrange these names alphabetically, and add the word ether.
• For symmetrical ethers, name the alkyl group and add the
prefix di-.
Nomenclature
• More complex ethers are named using the IUPAC system. One
alkyl group is named as a hydrocarbon chain, and the other is
named as part of a substituent bonded to that chain.
• Name the simpler alkyl group + O atom as an alkoxy substituent by
changing the -yl ending of the alkyl group to -oxy.
• Name the remaining alkyl group as an alkane, with the alkoxy group as
a substituent bonded to this chain.
Answer: 4-ethoxyoctane
Physical Properties
 Alcohols, ethers, and epoxides exhibit dipole–dipole
interactions because they have a bent structure with two
polar bonds.
 Alcohols are also capable of intermolecular hydrogen
bonding, because they possess a hydrogen atom on an
oxygen, making alcohols much more polar than ethers
and epoxides.
Physical Properties
 For compounds of comparable molecular weight, the
stronger the intermolecular forces, the higher the
boiling point or melting point.
• Alcohols and Ethers have higher boiling points and melting
points than hydrocarbons of comparable size and shape.
• Ethers have lower melting points and boiling points than
alcohols of comparable size and shape.
• Boiling point increase as the extent of hydrogen bonding
increases.
Physical Properties
 Solubility
• Alcohols, ethers, and epoxides having ≤ 5 C’s are H2O soluble
because they each have an oxygen atom capable of hydrogen
bonding to H2O.
• Alcohols, ethers, and epoxides having > 5 C’s are H2O insoluble
because the nonpolar alkyl portion is too large to dissolve in
H2O.
• Alcohols, ethers, and epoxides of any size are soluble in
organic solvents.
Interesting Alcohols
 Ethanol (CH3CH2OH), formed by the fermentation of the
carbohydrates in grains, grapes, and potatoes, is the alcohol
present in alcoholic beverages.
• It is perhaps the first organic compound synthesized by humans, because
alcohol production has been known for at least 4000 years.
• Ethanol depresses the central nervous system, increases the production of
stomach acid, and dilates blood vessels, producing a flushed appearance.
• Ethanol is also a common laboratory solvent, which is sometimes made
unfit to ingest by adding small amounts of benzene or methanol (both of
which are toxic).
• Ethanol is a common gasoline additive, widely touted as an
environmentally friendly fuel source.
 Methanol (CH3OH) is also called wood alcohol, because it can be
obtained by heating wood at high temperatures in the absence of
air. Methanol is extremely toxic because of the oxidation products
formed when it is metabolized in the liver. Ingestion of as little as
15 mL causes blindness, and 100 mL causes death.
 2-Propanol [(CH3)2CHOH] is the major component of rubbing
alcohol. When rubbed on the skin it evaporates readily, producing
a pleasant cooling sensation. Because it has weak antibacterial
properties, 2-propanol is used to clean skin before minor surgery
and to sterilize medical instruments.
 Ethylene glycol (HOCH2CH2OH) is the major component of
antifreeze. It is readily prepared from ethylene oxide. It is sweet
tasting but toxic.
 Glycerol [(HOCH2)2CHOH] is used in lotions, liquid soap, and
shaving cream. Since it is sweet tasting and nontoxic, it is also an
additive in candy and some prepared foods. Its three OH groups
readily hydrogen bond to water, so it helps to retain moisture in
these products.
Interesting Ethers
 The discovery that diethyl ether (CH3CH2OCH2CH3) is a
general anesthetic revolutionized surgery in the
nineteenth century.
• Diethyl ether is an imperfect anesthetic, but considering the
alternatives in the nineteenth century, it was a miracle drug.
• It is safe, easy to administer, and causes little patient
mortality, but it is highly flammable and causes nausea in many
patients.
• For these reasons, alternatives to diethyl ether are now widely
used.
 Many of these newer general anesthetics, which cause little patient
discomfort, are also ethers. These include isoflurane, enflurane, and
methoxyflurane.
 Replacing some of the hydrogen atoms in the ether by halogens results
in compounds with similar anesthetic properties but decreased
flammability.
Interesting Epoxides
 Although epoxides occur less widely in natural products than
alcohols or ethers, interesting and useful epoxides are also
known.
 As an example, two recently introduced drugs that contain
an epoxide are eplerenone and tiotropium bromide.
• Eplerenone is prescribed to reduce cardiovascular risk in patients
who have already had a heart attack.
• Tiotropium bromide is a long-acting bronchodilator used to treat the
chronic obstructive pulmonary disease of smokers and those
routinely exposed to secondhand smoke.
Preparation of Alcohols, Ethers, and Epoxides
 Alcohols and ethers are both common products of
nucleophilic substitution. They are synthesized from
alkyl halides.
Reactions of Alcohols
 Alcohols undergo two useful reactions; dehydration
and oxidation.
 Dehydration
• When an alcohol is treated with a strong acid such as H2SO4,
the elements of water are lost and an alkene is formed as
product.
• Loss of H2O from a starting material is called dehydration.
• Dehydration takes place by breaking bonds on two adjacent
atoms; the C—OH bond and an adjacent C—H bond.
• Dehydration is an example of a general type of organic reaction
called an elimination reaction.
• Elimination is a reaction in which elements of the starting material are
“lost” and a new multiple bond is formed.
Ethanol
Reactions of Alcohols
 Oxidation
• To determine if an organic compound has been oxidized, we
compare the relative number of C—H and C—O bonds in the
starting material and product.
• Oxidation results in an increase in the number of C—O bonds
or a decrease in the number of C—H bonds.
• An organic compound like CH4 can be oxidized by replacing C—
H bonds with C—O bonds. Organic chemists use the symbol [O]
to indicate oxidation.
Reactions of Alcohols
• Alcohols can be oxidized to a variety of compounds, depending
on the type of alcohol and the reagent.
• Oxidation occurs by replacing the C—H bonds on the carbon
bearing the OH group by C—O bonds.
• All oxidation products from alcohol starting materials
contain a C=O, a carbonyl group.
• Primary (1°) alcohols are first oxidized to aldehydes (RCHO),
which are further oxidized to carboxylic acids (RCOOH) by
replacing one and then two C—H bonds by C—O bonds.
• Secondary (2°) alcohols are oxidized to ketones (R2CO), by
replacing one C—H bond by one C—O bond.
• Tertiary 3° alcohols have no H atoms on the carbon with the
OH group, so they are not oxidized.
Oxidation and Blood Alcohol Screening
 A common reagent for alcohol oxidation is potassium
dichromate, K2Cr2O7, a red-orange solid.
 Oxidation with this chromium reagent is characterized by
a color change, as the red-orange reagent is reduced to
a green Cr3+ product.
 The first devices used to measure blood alcohol content
in individuals suspected of “driving under the influence,”
made use of this color change.
Oxidation and Blood Alcohol Screening
 The oxidation of CH3CH2OH with K2Cr2O7 to form
CH3COOH and Cr3+ was the first available method for the
routine testing of alcohol concentration in exhaled air.
Some consumer products for alcohol screening are still
based on this technology.
 A driver is considered “under the influence” in most
countries with a blood alcohol concentration of 0.08%.
• Values may vary.
The Metabolism of Ethanol
 When ethanol is consumed, it is quickly absorbed in the
stomach and small intestines and then rapidly
transported in the bloodstream to other organs.
 Ethanol is metabolized in the liver, by a two-step
oxidation sequence.
 High molecular weight enzymes, alcohol dehydrogenase
and aldehyde dehydrogenase, and a small molecule
called a coenzyme carry out these oxidations.
The Metabolism of Ethanol
 The products of the biological oxidation of ethanol are
the same as the products formed in the laboratory. When
ethanol (CH3CH2OH, a 1° alcohol) is ingested, it is
oxidized in the liver first to CH3CHO (acetaldehyde), and
then to CH3COOH (acetic acid).
 If more ethanol is ingested than can be metabolized in a
given time period, the concentration of acetaldehyde
accumulates. This toxic compound is responsible for the
feelings associated with a hangover.
Reactions of Ethers
 Ethers have a poor leaving group, so they cannot undergo
nucleophilic substitution or elimination reactions directly.
 Instead, they must first be converted to a good leaving group
by reaction with strong acids. Only HBr and HI can be used,
though, because they are strong acids that are also sources
of good nucleophiles (Br– and I–, respectively).
 When ethers react with HBr or HI, both C—O bonds are
cleaved and two alkyl halides are formed as products.
Amines and Amids
Amines; Introduction, Structure and Classification, Nomenclature, Physical Properties, Amines as
Bases, Reaction of Amines with Acids, Ammonium Salts, Ammonium Salts as Useful Drugs
Amides; Naming an Amide, Physical Properties, Amide hydrolysis, Interesting Amines and Amids,
Epinephrine and related compounds, Penicillin
Introduction
 Amines are organic nitrogen compounds, formed by
replacing one or more hydrogen atoms of ammonia
(NH3) with alkyl groups.
 Like ammonia, the amine nitrogen atom has a
nonbonded electron pair, making it both a base and a
nucleophile. As a result, amines react with electrophiles
to form ammonium salts; compounds with four bonds to
nitrogen.
Structure and Classification
 Amines are classified as 1°, 2°, or 3° by the number of
alkyl groups bonded to the nitrogen atom.
• A primary (1°) amine has one C—N bond and the general
structure RNH2.
• A secondary (2°) amine has two C—N bonds and the general
structure R2NH.
• A tertiary (3°) amine has three C—N bonds and the general
structure R3N.
Like ammonia, the amine nitrogen atom has a lone pair of electrons, which is
generally omitted in condensed structures. An amine nitrogen atom is surrounded
by three atoms and one nonbonded electron pair, making it trigonal pyramidal in
shape, with bond angles of approximately 109.5°.
Structure and Classification
 The amine nitrogen can also be part of a ring.
• Aliphatic and aromatic amines.
 The structures of morphine and atropine, two alkaloids;
naturally occurring amines derived from plant sources.
 Each alkaloid contains a nitrogen atom in a ring.
• The analgesic and narcotic effects of opium are due largely to the
alkaloid morphine.
• Atropine is isolated from Atropa belladonna, the deadly nightshade
plant. Atropine dilates pupils, increases heart rate, and relaxes
smooth muscles.
Nomenclature
 To name a primary (1°) amine, name the alkyl group
bonded to the nitrogen atom and add the suffix -amine,
forming a single word.
 For 2° and 3° amines with different alkyl groups,
alphabetize the names of the alkyl groups. 2° and 3°
amines having identical alkyl groups are named by using
the prefix di- or tri- with the name of the primary
amine.
Answer: Pentylamine
Answer: ethylmethylamine
Aromatic amines, amines having a nitrogen atom
bonded directly to a benzene ring, are named as
derivatives of aniline. Use the prefix N- before any alkyl
group bonded to the amine nitrogen.
Physical Properties
 Many low molecular weight amines have very foul odors.
• Trimethylamine [(CH3)3N], formed when enzymes break down
certain fish proteins, has the characteristic odor of rotting fish.
• Cadaverine (NH2CH2CH2CH2CH2CH2NH2) is a poisonous diamine
with a putrid odor also present in rotting fish, and partly
responsible for the odor of semen, urine, and bad breath.
Physical Properties
 Because nitrogen is much more electronegative than carbon
or hydrogen, amines contain polar C—N and N—H bonds.
Primary (1°) and 2° amines are also capable of
intermolecular hydrogen bonding, because they contain
N—H bonds.
 In comparing compounds of similar size, 1° and 2° amines
have higher boiling points than compounds incapable of
hydrogen bonding, but lower boiling points than alcohols that
have stronger intermolecular hydrogen bonds.
Tertiary (3°) amines have lower boiling points than 1° and 2° amines
of comparable size, because they have no N—H bonds.
Physical Properties
 Amines are soluble in organic solvents regardless of size.
Amines with fewer than six carbons are water soluble
since they can hydrogen bond with water.
 Larger amines are water insoluble since the nonpolar
alkyl portion is too large to dissolve in the polar water
solvent.
Amines as Bases
 Like ammonia (NH3), amines are bases; that is, they are
proton acceptors.
• When an amine is dissolved in water, an acid–base reaction
occurs: the amine accepts a proton from H2O, forming its
conjugate acid, an ammonium ion, and water loses a proton,
forming hydroxide, –OH.
• While amines are more basic than other families of organic compounds,
they are weak bases compared to inorganic bases like NaOH.
Reaction of Amines with Acids
 Amines also react with acids such as HCl to form
water-soluble salts.
 The lone pair of electrons from the amine nitrogen atom
is always used to form a new bond to a proton from the
acid.
 The amine [(CH3)3N] gains a proton to form its conjugate acid, an
ammonium cation [(CH3)3NH+].
 A proton is removed from the acid (HCl) to form its conjugate
base, the chloride anion (Cl–).
 In an acid–base reaction of an amine, the amine nitrogen
always forms a new bond to a proton forming an ammonium
ion.
Ammonium Salts
 When an amine reacts with an acid, the product is an
ammonium salt: the amine forms a positively charged
ammonium ion and the acid forms an anion.
• To name an ammonium salt, change the suffix -amine of the
parent amine from which the salt is formed to the suffix ammonium. Then add the name of the anion.
Name the ammonium salt: (CH3)3NH+ CH3COO−
Answer: trimethylammonium acetate
Ammonium Salts
 Ammonium salts are ionic compounds, and as a result:
• Ammonium salts are water-soluble solids.
• In this way, the solubility properties of an amine can be
changed by treatment with acid.
• For example, octylamine has eight carbons, making it water
insoluble.
• Reaction with HCl forms octylammonium chloride. This ionic
solid is now soluble in water.
Ammonium Salts as Useful Drugs
 Many amines with useful medicinal properties are sold as
their ammonium salts. Since the ammonium salts are
more water soluble than the parent amine, they are
easily transported through the body in the aqueous
medium of the blood.
• Diphenhydramine is a 3° amine that is sold as its ammonium salt. Its
salt is formed by treating diphenhydramine with HCl
(diphenhydramine hydrochloride), is an over-the-counter
antihistamine that is used to relieve the itch and irritation of skin
rashes and hives.
Amides
 Amides contain a carbonyl group bonded to a nitrogen
atom.
 The N atom of an amide may be bonded to other
hydrogen atoms or alkyl groups.
 Amides are classified as 1°, 2°, or 3° depending on the
number of carbon atoms bonded directly to the nitrogen
atom.
 A primary (1°) amide contains one C—N bond. A 1° amide has
the structure RCONH2.
 A secondary (2°) amide contains two C—N bonds. A 2° amide has
the structure RCONHR'.
 A tertiary (3°) amide contains three C—N bonds. A 3° amide has
the structure RCONR'2.
Naming an Amide
 In the IUPAC system, amides are identified by the
suffix -amide.
Naming an Amide
 A 2° or 3° amide has two parts to its structure: the RCO–
group that contains the carbonyl and one or two alkyl
groups bonded to the nitrogen atom.
 To name a 2° or 3° amide,
• Name the alkyl group (or groups) bonded to the N atom of the
amide. Use the prefix “N-” preceding the name of each alkyl
group.
• Name the RCO– group with the suffix -amide.
Name the following amide: HCONHCH2CH3.
Answer: N-ethylformamide
Physical Properties
 1° and 2° amides have higher boiling points and melting
points than esters and 3° amides of comparable size.
 Amides having fewer than six carbons are soluble in
water.
 Higher molecular weight amides are insoluble in water
because the nonpolar portion of the molecule, the C—C
and C—H bonds, gets larger than the polar carbonyl
group.
Amide Hydrolysis
 Treatment of an amide (RCONHR') with water in the
presence of an acid catalyst (HCl) forms a carboxylic acid
(RCOOH) and an ammonium salt (R'NH3+Cl–).
Amide Hydrolysis
 Amides are also hydrolyzed in aqueous base to form
carboxylate anions and a molecule of ammonia (NH3) or
amine.
Interesting Amines and Amides
 Caffeine and nicotine are widely used stimulants of the
central nervous system that contain nitrogen atoms in
rings. Caffeine and nicotine, like the amines, are
alkaloids, naturally occurring amines derived from
plant sources.
Epinephrine and Related Compounds
 Epinephrine, or adrenaline as it is commonly called, is
an amine synthesized in the adrenal glands from
norepinephrine (noradrenaline).
Epinephrine and Related Compounds
 When an individual senses danger or is confronted by stress,
the hypothalamus region of the brain signals the adrenal
glands to synthesize and release epinephrine, which enters
the bloodstream and then stimulates a response in many
organs.
• Epinephrine synthesis occurs in the interior of the adrenal gland.
 Epinephrine release causes; increase in heart rate, increase
in blood pressure, increase in glucose synthesis, dilation of
lung passages.
Epinephrine and Related Compounds
 The search for drugs that were structurally related to
epinephrine but exhibited only some components of its
wide range of biological activities led to the discovery of
some useful medications.
 Both albuterol and salmeterol dilate lung passages; that
is, they are bronchodilators. They do not, however,
stimulate the heart. This makes both compounds useful
for the treatment of asthma.
Penicillin
 The antibiotic properties of penicillin were first
discovered in 1928 by Sir Alexander Fleming, who noticed
that a mold of the genus Penicillium inhibited the
growth of certain bacteria.
 The penicillins are a group of related antibiotics. All
penicillins contain two amide units. One amide is part of
a four-membered ring called a 𝛃-lactam. The second
amide is bonded to the four-membered ring.
Penicillin
 The first penicillin to be discovered was penicillin G.
Amoxicillin is another example in common use today.
 Penicillin interferes with the synthesis of the bacterial
cell wall.
Thiols and Sulfides
Introduction, Reactions of Thiols, Sulfides, Dimethyl Sulfoxide
Introduction
 Thiols contain a sulfhydryl group (SH –
mercapto group) bonded to a
tetrahedral carbon.
 The sulfur atom in thiols have two lone
pairs of electrons, so each heteroatom is
surrounded by eight electrons.
Thiols differ from alcohols in one important way. They contain no O—H bonds,
so they are incapable of intermolecular hydrogen bonding. This gives thiols
lower boiling points and melting points compared to alcohols having the
same size and shape. The most obvious physical property of thiols is their
distinctive foul odor. 3-Methyl-1-butanethiol [(CH3)2CHCH2CH2SH] is one of
the main components of the defensive spray of skunks.
Reactions of Thiols
 Thiols undergo one important reaction: thiols are
oxidized to disulfides, compounds that contain a
sulfur–sulfur bond. This is an oxidation reaction because
two hydrogen atoms are removed in forming the
disulfide.
Reactions of Thiols
 Disulfides can also be converted back to thiols with a
reducing agent.
 The symbol for a general reducing agent is [H], since
hydrogen atoms are often added to a molecule during
reduction.
Reactions of Thiols
 The chemistry of thiols and disulfides plays an important
role in determining the properties and shape of some
proteins.
 For example, α-keratin, the protein in hair, contains
many disulfide bonds.
 Straight hair can be made curly by cleaving the disulfide
bonds in α-keratin, then rearranging and re-forming
them.
To make straight hair curly, the disulfide bonds holding the protein
chains together are reduced. This forms free SH groups. The hair is
turned around curlers and then an oxidizing agent is applied. This reforms the disulfide bonds to the hair, now giving it a curly appearance.
Sulfides
 In organic chemistry, "sulfide" usually refers
to the linkage C—S—C, although the term
thioether is less ambiguous. For example, the
thioether dimethyl sulfide is CH3—S—CH3.
 Methionine, an amino acid that also
participates in the building of the proteins is
the most important thioether.
Methionine
(Met or M)
Sulfides
 A disulfide bond is a single covalent bond derived from the
coupling of thiol groups. The linkage is also called an SS-bond
or disulfide bridge. The overall connectivity is therefore C—
S—S—C.
 Acid compounds containing (SOH) groups are distinguished by
the number of oxygen atoms within that group as follows:
• RSOH selfenic acid
• RSO2H sulfinic acid
• RSO3H sulfonic acid
Sulfides
 A sulfenic acid is a sulfur compound and oxoacid with the general
formula RSOH. Sulfenic acids are generally unstable.
 Sulfinic acids are oxoacids of sulfur with the structure RSO(OH).
 Sulfonic acid is a hypothetical acid with formula H-S(=O)2-OH.
• This compound is a tautomer of sulfurous acid HO-S(=O)-OH, but less
stable, and would likely convert to that very quickly if it were formed.
• Although this compound is unimportant, there are many derived
compounds, with formula R-S(=O)2-OH for various R. These may then
form salts or esters, called sulfonates.
• Sulfonic esters are considered good leaving groups in nucleophilic
aliphatic substitution.
Dimethyl Sulfoxide
 Dimethyl sulfoxide (DMSO) is the chemical compound with
the formula (CH3)2SO.
 This colorless liquid is an important polar aprotic solvent
that dissolves both polar and nonpolar compounds and is
miscible in a wide range of organic solvents as well as
water.
• Polar aprotic solvents are solvents that lack an acidic hydrogen.
 It has a distinctive property of penetrating the skin very
readily, allowing the handler to taste it. Some describe it as
an "oyster-like" taste, others claim it tastes like garlic.
Dimethyl Sulfoxide
 DMSO is an important polar aprotic solvent. It is less
toxic than other members of this class such as
dimethylformamide. Because of its excellent solvating
power, DMSO is frequently used as solvent for chemical
reactions involving the reactions of salts.
 DMSO is used in the PCR reaction to inhibit secondary
structures in the DNA template or the DNA primers.
However, use of DMSO in PCR increases the mutation
rate.
Dimethyl Sulfoxide
 In cryobiology DMSO has been used as a cryoprotectant
and is still an important constituent of cryoprotectant
vitrification mixtures used to preserve organs, tissues,
and cell suspensions.
 It is particularly important in the freezing and long-term
storage of embryonic stem cells and hematopoietic stem
cells, which are often frozen in a mixture of 10% DMSO
and 90% fetal calf serum.
Dimethyl Sulfoxide
 In the medical field DMSO is predominantly used as a topical
analgesic, a vehicle for topical application of pharmaceuticals, as
an anti-inflammatory and an antioxidant.
 Because DMSO easily penetrates the skin, substances dissolved in
DMSO may be quickly absorbed. For instance, a solution of sodium
cyanide in DMSO can cause cyanide poisoning through skin
contact. DMSO by itself has low toxicity.
• Dimethyl sulfoxide can produce an explosive reaction when exposed to acid chlorides.
Recently, it was found that DMSO waste disposal into sewers can cause environmental
odor problems in cities.
• Waste water bacteria transform DMSO under hypoxic (anoxic) conditions into dimethyl
sulfide (DMS) that is slightly toxic and has a strong disagreeable odor, similar to rotten
cabbage.
Reference Books
 Eren, M. 2015. Organic Chemistry Lecture Notes (in TR)
• Thanks very much, Prof. Dr. Meryem EREN.
 Fromm JR. "http://www.3rd1000.com/chem301/chem301x.htm" Date of
access: 14.12.2016
 Smith JG (2010). Organic Chemistry, 3rd Edition, McGraw-Hill.
 Smith JG (2012). General, Organic, & Biological Chemistry 2nd Edition,
McGraw-Hill.