CH105: Consumer Chemistry

Chapter 10 – Compounds with Sulfur, Phosphorus, and Nitrogen

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Opening Essay – Organic Chemicals as Agents of War

Development of the first chemotherapy drug

10.1 Compounds Containing Sulfur

10.2 Compounds Containing Phosphorous

10.3 Compounds Containing Nitrogen

Opening Essay – Organic Chemicals as Agents of War

Recall that a heteroatom is any atom other than carbon or hydrogen that is found in an organic molecule. In the previous chapter, we were introduced to compounds that contain oxygen. In this chapter, we will focus on compounds that contain nitrogen, suflur, and phosphorous. Compounds that contain these unique heteroatoms have been used in a variety of ways, including highly deadly and destructive ones. Small organic molecules that contain heteroatoms, such as nitrogen, phosphorous and sulfur, have been used to create chemical warfare agents. This includes the sulfur mustards, nitrogen mustards, and organophosphates (like Sarin Gas), represented by the compounds below:

Mustard Gas

Sulfur mustard is the prototypical substance of the sulfur-based family of cytotoxic warfare agents which have the ability to form large blisters on exposed skin and in the lungs. Pure sulfur mustards are colorless, viscous liquids at room temperature. When used in impure form, such as warfare agents, they are usually yellow-brown and have an odor resembling mustard plants, garlic, or horseradish, hence the name. Sulfur mustard was originally assigned the name LOST, after the scientists Wilhelm Lommel and Wilhelm Steinkopf, who developed a method of large-scale production for the Imperial German Army in 1916.

Mustard agents are regulated under the 1993 Chemical Weapons Convention. Three classes of chemicals are monitored under this Convention, with sulfur and nitrogen mustard grouped in Schedule 1, as substances with no use other than in chemical warfare. Mustard agents could be deployed on the battlefield by means of artillery shells, aerial bombs, rockets, or by spraying from warplanes.

Figure 10.1 Use of Mustard Gas During World Wars I and II. A. US Army World War II Gas Identification Poster, ca. 1941–1945. B. Blisters on a human arm created by exposure to mustard gas.

Photo of Identification Poster provided by: US Army. Photo of Blisters provided by: ClockworkSoul

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Development of the first chemotherapy drug

As early as 1919 it was known that mustard agents supress hematopoiesis, or the formation of blood cells. In addition, autopsies performed on 75 soldiers who had died of mustard agent during World War I were done by researchers from the University of Pennsylvania who reported decreased counts of white blood cells. This led the American Office of Scientific Research and Development (OSRD) to finance the biology and chemistry departments at Yale University to conduct research on the use of chemical warfare during World War II. As a part of this effort, the group investigated nitrogen mustard as a therapy for Hodgkin’s lymphoma and other types of lymphoma and leukemia, and this compound was tried out on its first human patient in December 1942. The results of this study were not published until 1946, when they were declassified.In a parallel track, after the air raid on Bari in December 1943, the doctors of the U.S. Army noted that white blood cell counts were reduced in their patients. Some years after World War II was over, the incident in Bari and the work of the Yale University group with nitrogen mustard converged, and this prompted a search for other similar chemical compounds. Due to its use in previous studies, the nitrogen mustard called “HN2”, later known as mustine, became the first cancer chemotherapy drug to be used. Mustine (HN2), is no longer commonly in use because of excessive toxicity.

Organophosphate Nerve Agents

Sarin is an organophosphate nerve agent. Like all other nerve agents, sarin attacks the nervous system by interfering with the degradation of the neurotransmitter acetylcholine at neuromuscular junctions. Death will usually occur as a result of asphyxia due to the inability to control the muscles involved in breathing function.

Initial symptoms following exposure to sarin are a runny nose, tightness in the chest and constriction of the pupils. Soon after, the person will have difficulty breathing and they will experience nausea and drooling. As they continue to lose control of bodily functions, they may vomit, defecate and urinate. This phase is followed by twitching and jerking. Ultimately, the person becomes comatose and suffocates in a series of convulsive spasms. Moreover, common mnemonics for the symptomatology of organophosphate poisoning, including sarin gas, are the “killer B’s” of bronchorrhea and bronchospasm because they are the leading cause of death, and SLUDGE – salivation, lacrimation, urination, defecation, gastrointestinal distress, and emesis. Death may follow in 1 to 10 minutes after direct inhalation.

Sarin has a high volatility (ease with which a liquid can turn into a gas) relative to similar nerve agents, therefore inhalation can be very dangerous and even vapor concentrations may immediately penetrate the skin. A person’s clothing can release sarin for about 30 minutes after it has come in contact with sarin gas, which can lead to exposure of other people. Production and stockpiling of sarin was outlawed as of April 1997 by the Chemical Weapons Convention of 1993, and it is classified as a Schedule 1 substance. The suspected use of sarin in recent bombing attacks in Syria remains a controversial topic in global politics.

Oxygen is the most common and plentiful heteroatom found in organic molecules and is a constituent of all the major macromolecules found in the human body (proteins, carbohydrates, fats/lipids, and nucleic acids). In addition to oxygen, sulfur, phosphorous and nitrogen are also common heteroatoms that have special roles in biological systems. Nitrogen is a key component in proteins and phosphorous is found in deoxyribonucleic acid (DNA), and ribonucleic acid (RNA). Sulfur is found in more limited quantities in protein, as well as in many other small molecules found in the human body, including several vitamins. Sulfur-containing organic compounds are also required for the biosynthesis of many chemical signaling molecules such as hormones and neurotransmitters. Thus, this chapter will focus on organic functional groups and the associated chemical reactions associated with nitrogen, sulfur, and phosphorus containing molecules.

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10.1 Compounds Containing Sulfur

Thiols and Disulfides

Because sulfur is in the same group (6A) of the periodic table as oxygen, the two elements have some similar properties. We might expect sulfur to form organic compounds related to those of oxygen, and indeed it does. Thiols (also called mercaptans), are sulfur analogs of alcohols and have the general formula R-SH. For example, methanethiol (also called methyl mercaptan), has the formula CH₃SH. Ethanethiol (ethyl mercaptan or CH₃CH₂SH) is the most common odorant for liquid propane (LP) gas. Its structure parallels that of ethanol, but with sulfur in place of oxygen. The odor of CH₃CH₂SH is infamous. Ethanethiol is more volatile than ethanol due to a diminished ability to engage in hydrogen bonding. Ethanethiol is toxic. It occurs naturally as a minor component of petroleum, and is commonly added to otherwise odorless gaseous products such as liquefied petroleum gas (LPG), at very low doses, to help warn of gas leaks. At these concentrations, ethanethiol is not harmful.

Thiols can undergo mild oxidation to produce compounds called disulfides. This type of reaction is common in protein structures where it forms intramolecular disulfide bridge structures. The amino acids cysteine [HSCH₂CH(NH₂)COOH] and methionine [CH₃SCH₂CH₂CH(NH₂)COOH] contain sulfur atoms, as do all proteins that contain these amino acids. Disulfide linkages (–S–S–) between protein chains are extremely important in protein structure.

Figure 10.2 The formation of disulfides from thiol structures. A. depicts a generic equation for the formation of a disulfide from two thiol molecules. Note that during this reaction an oxidizing reagent is required to remove 2 hydrogens and 2 electrons from the thiol structures in order to form the oxidized disulfide product. B. Shows two cysteine amino acids that have formed a disulfide bond. C. When cysteine occurs in protein sequences it can react with other cysteine residues within the structure and form internal protein structures called disulfide bridges. Disulfide bridges are important in maintaining the correct 3-dimentional structure, and thus, the overall function of proteins within biological systems.

Depiction of disulfide protein bridges in C, provided by: Jü

Disulfide Bonds in Hair and Feathers - A Closer Look

Over 90% of the dry weight of hair comprises proteins called keratins, which have a high disulfide content, from the amino acid cysteine.

The robustness conferred in part by disulfide linkages is illustrated by the recovery of virtually intact hair from ancient Egyptian tombs. Feathers have similar keratins and are extremely resistant to protein digestive enzymes. Different parts of the hair and feather have different cysteine levels, leading to harder or softer material. Manipulating disulfide bonds in hair is the basis for the permanent wave in hairstyling. Reagents that affect the making and breaking of S–S bonds are key, e.g., ammonium thioglycolate. The high disulfide content of feathers dictates the high sulfur content of bird eggs. The high sulfur content of hair and feathers contributes to the disagreeable odor that results when they are burned.

Figure 10.3 The importance of disulfide bridges. Disulfide bonds are highly abundant in hair and feathers. A. Depicts a 200X magnification of a human hair. B. Shows the structure of a feather without any coloration. C. Shows a permanent hair-style.

Photo of magnified human hair is provided by: Jan Homann Photo of the feather provided by: Rita Ballantyne Photo of permanent hair-style provided by: LJP Assistant

In the hair protein, keratin, disulfide bonds are formed by oxidation of the sulfhydryl groups on cysteine. Different protein chains or loops within a single chain are held together by the strong covalent disulfide bonds. In the permanent wave process, a basic reducing substance (usually ammonium thioglycolate) is first added to reduce and disrupt the disulfide cross-links.

Figure 10.4 First Step in Receiving a Permanent Hair Treatment. The hair is first rolled tight onto curlers. The first reagent, a basic reducing agent is then added to the hair. The reducing agent disrupts the disulfide bonds in the keratin hair proteins, allowing the folding pattern of the keratin to shift and accommodate the curled hair structure.

To stabilize the hair in the new position an oxidizing agent, usually a dilute solution of hydrogen peroxide, (also called the neutralizer) is added to reform the disulfide bonds in their new positions. The permanent will hold these new disulfide bond positions until the hair grows out. The new hair growth has not been treated and will thus, adopt it’s natural disulfide bond structure.

Figure 10.5 Second Step in a Permanent Hair Treatment. After treatment of the curled hair with the reducing agent. An oxidizing agent is added to the hair to reform the disulfide bridges while the hair is in the curled position. Upon unrolling the hair, the hair will now retain the curly conformation due to the formation of the new disulfide bridges.

Thioethers

Thioethers, which are sulfur analogs of ethers, have the form general formula RSR′. The sulfur mustard in the opening essay is an example of a thioether. A similar, but nontoxic thioether is dimethylsulfide (CH₃SCH₃), which is responsible for the sometimes unpleasant odor of cooking cabbage and related vegetables.

Thioesters

Similar to alcohols, thiols can also react with carboxylic acids in a dehydration reaction to form an ester structure. In this case, the -OH group from the carboxylic acid acts as a leaving group following the nucleophilic attack of the sulfur at the carbonyl carbon. The resulting product is called a thioester. The general structure of a thioester is shown below:

The dehydration reaction needed to form a thioester is shown below:

The formation of thioesters are very important in biological systems, especially with regards to fat metabolism. Long chain fatty acids cannot be carried through the cell as a free fatty acid. The carboxylic acid structure would be damaging to the integrity of the cell membrane. Thus, fatty acids are shuttled safely within the cell as a thioester with an important organic molecule known as coenzyme A. The structure of coenzyme A is quite large and complex. However, the important active component is the key thiol group indicated with the arrow.

In fact, coenzyme A is often abbreviated HSCoA, in order to emphasize that it is the thiol sulfur that provides the critical thioester linkage to fatty acid groups. When a fatty acid is attached to coenzyme A, the fatty acid group is called a fatty acyl- or more simply an acyl- group. An example of a C₁₆ fatty acid that has been activated and linked with Coenzyme A is shown below:

When your food (carbohydrate and fat) is broken down in your body, it is eventually converted to a simple two-carbon unit called acetyl CoA, which is essentially a thioester derivative of acetic acid:

Acetyl-CoA is then utilized in a complex metabolic cycle, called the Kreb Cycle, to produce large quantities of Adenosine Triphosphate (ATP). ATP is the main source of energy that keeps your cells alive and functioning.

Key Takeaway

Thiols, disulfides, thioethers, and thioesters are common in biological compounds.

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10.2 Compounds Containing Phosphorous

Just as carboxylic acids do, inorganic acids such phosphoric acid (H₃PO₄) also form esters. The esters of phosphoric acid are especially important in biochemistry. Note that phosphoric acid contains three alcohol positions and one position which has a double-bonded oxygen. Thus, unlike a carboxylic acid that only contains one alcohol position, a phosphoric acid molecule can form a mono-, di-, or tri phosphoester by reaction with one, two, or three molecules of an alcohol. The formation of a phosphoester is also a dehydration reaction that is characterized by the loss of water.

If ethanol (CH₃CH₂OH) was the alcohol reacting with phosphoric acid, the three potential products would be:

Esters of pyrophosphoric acid and triphosphoric acid are also important in biochemistry.

Esters of these acids are present in every plant and animal cell. They are biochemical intermediates in the transformation of food into usable energy. The bonds between phosphate units in adenosine triphosphate (ATP) are called phosphoanhydride bonds. These are high-energy bonds that store energy from the metabolism of foods. Most cellular functions need energy in order to be carried out: synthesis of proteins, synthesis of membranes, movement of the cell, cellular division, transport of various solutes etc. The ATP is the molecule that carries energy to the place where the energy is needed. When ATP is hydrolyzed into ADP (Adenosine diphosphate) and P_i (phosphate), the breakdown of the last covalent link of phosphate (a simple -PO₄) liberates energy that is used in reactions where it is needed.

Phosphate esters are also important structural constituents of phospholipids and nucleic acids, DNA and RNA. In the next chapter, you will be introduced to the major macromolecules of the body and will revisit the phosphoester linkages found in DNA, RNA, and the phospholipids.

Key Takeaway

Inorganic acids such as H₃PO₄ form esters. The esters of phosphoric acid are especially important in biochemistry.

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10.3 Compounds Containing Nitrogen

Amines

Classification and Properties

An amine is any compound that has one or more organic groups bonded to a nitrogen atom. Recall that nitrogen atoms have 5 electrons in their valence shell. Thus, they tend to form three covalent bonds and have one lone pair of electrons associated with them.

Amines are classified according to the number of carbon atoms bonded directly to the nitrogen atom. A primary (1°) amine has one carbon (alkyl) group attached to the nitrogen atom, a secondary (2°) amine has two, and a tertiary (3°) amine has three.

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Figure 10.6 The Structure of Amines Compared to Water, an Alcohol, and an Ether

This differs from the way that we classified alcohols as primary, secondary and tertiary. To classify alcohols, we look at the number of carbon atoms bonded to the carbon atom bearing the OH group, not the oxygen atom itself. Thus, although isopropylamine looks similar to isopropyl alcohol, the former is a primary amine, while the latter is a secondary alcohol. Note that both primary and secondary amines have hydrogen atoms attached to the nitrogen. Thus, they can both participate in hydrogen bonding. This causes primary and secondary amines to have higher boiling points than alkanes of similar size. However, because nitrogen has less electronegativity than oxygen, primary and secondary amines have lower boiling points than alcohols of similar size. All amines can form hydrogen bonds with water due to the lone pair of electrons on the nitrogen atom. Due to the polarity of the amine, amines with up to six carbons are soluble in water.

Interestingly, due to the lone pair of electrons that nitrogen has, they can also form a coordinate covalent bond. Recall that a coordinate covalent bond is one where a single atom shares two electrons with another atom that doesn’t bring any electrons into the shared bond. When nitrogen forms a bond with a fourth group through this lone pair of electrons, the resulting molecule is called a quaternary ammonium ion. This ion has a positive charge and can for ionic bonds with common anions.

Summary

An amine is a derivative of ammonia in which one, two, or all three hydrogen atoms are replaced by hydrocarbon groups. The amine functional group is as follows:

Amines are classified as primary, secondary, or tertiary by the number of hydrocarbon groups attached to the nitrogen atom. Amines are named by naming the alkyl groups attached to the nitrogen atom, followed by the suffix –amine.

Key Takeaways

Primary and secondary amines have higher boiling points than those of alkanes or ethers of similar molar mass because they can engage in intermolecular hydrogen bonding. Their boiling points are lower than those of alcohols because alcohol molecules have hydrogen atoms bonded to an oxygen atom, which is more electronegative.
The boiling points of tertiary amines, which cannot engage in hydrogen bonding because they have no hydrogen atom on the nitrogen atom, are comparable to those of alkanes and ethers of similar molar mass.
Because all three classes of amines can engage in hydrogen bonding with water, amines of low molar mass are quite soluble in water.

Concept Review Exercises

Which compound has the higher boiling point, CH₃CH₂CH₂CH₂CH₂NH₂ or CH₃CH₂CH₂CH₂CH₂CH₃? Explain.
Which compound is more soluble in water, CH₃CH₂CH₂CH₂CH₃ or CH₃CH₂NHCH₂CH₃? Explain.

Answers

CH₃CH₂CH₂CH₂CH₂NH₂ because the nitrogen-to-hydrogen (N–H) bonds can engage in hydrogen bonding; CH₃CH₂CH₂CH₂CH₂CH₃ cannot engage in hydrogen bonding
CH₃CH₂NHCH₂CH₃ because amines can engage in hydrogen bonding with water; alkanes cannot engage in hydrogen bonding

To Your Health: The Smell of Death

Amines have “interesting” odors. The simple ones smell very much like ammonia. Higher aliphatic amines smell like decaying fish. Or perhaps we should put it the other way around: Decaying fish give off odorous amines. The stench of rotting fish is due in part to two diamines: putrescine and cadaverine. They arise from the decarboxylation of ornithine and lysine, respectively, amino acids that are found in animal cells.

Example Problems:

Classify each compound as a primary, secondary, or tertiary amine.

CH₃CH₂CH₂NH₂
CH₃CH₂NHCH₂CH₃
CH₃CH₂CH₂NHCH₃

Solution

There is only one alkyl group attached to the nitrogen atom, so the amine is primary.
There are two methyl groups and one ethyl group on the nitrogen atom. The compound is a tertiary amine.
There are two ethyl groups attached to the nitrogen atom; the amine is secondary.
The nitrogen atom has a methyl group and a propyl group, so the compound is a secondary amine.

More Practice

Classify each compound as a primary, secondary, or tertiary amine..

CH₃CH₂CH₂CH₂NH₂
CH₃CH₂CH₂NHCH₂CH₂ CH₃

Solution

There is an isopropyl group (in red) and two methyl groups (in green) attached to the nitrogen atom; the amine is tertiary.

3. There is one n-butyl group and two hydrogens attached to the nitrogen atom; the amine is primary.

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The Basicity of Amines

The ability of the nitrogen to form coordinate covalent bonds accounts for many of the chemical features of amines. For example, the lone pair electrons of the nitrogen in amines enables them to act as a weak base. In this case, the nitrogen is acting as a Lewis base. A Lewis base, by definition, is any compound that can donate a pair of electrons to an acceptor. Typically, this will be a H⁺ (proton) that is donated from a water molecule or an acid. In the case of the water molecule, you can see that amines effectively increase the basicity (alkalinity) of water by increasing the concentration of hydroxide (OH^–) ions that are in solution. Note that amines are only weak bases, they do not fully ionize.

As a weak base, amines can also participate in acid-base neutralization reactions.

Amines in Aromatic and Heterocyclic Compounds

The primary amine in which the nitrogen atom is attached directly to a benzene ring has a special name—aniline. Aryl amines are named as derivatives of aniline. Like most volatile amines, aniline possesses the odor of rotten fish. It ignites readily, burning with a smoky flame characteristic of aromatic compounds.

Analine was first discovered by the destructive distillation of the dye, indigo. Soon after, analine was used to produce the first synthetic dye, mauveine. Other aniline-baed dyes (also known as azo dyes) followed, such as fuchsine and safranine.

Figure 10.7 Aniline and the Creation of Synthetic Dyes. A. Aniline was originally isolated from the decomposition of indigo. Following it’s isolation, aniline has been used to create several synthetic dyes including B. Mauveine, C. Fuchsine, and D. Safranine.

Photo of Indigo provided by: David Stroe, Photo of Mauveine provided by: Science Museum Group Collection, Photo of Fuchsine and Safranine provided by: LHcheM

Following on the early work with aniline as the starting material for building synthetic dyes, it was discovered that aniline also had analgesic or pain relieving properties. While the toxic side effects of aniline limited its widespread use, it sparked research on the medicinal properties of synthetic dyes. In 1932, Bayer Laboratories discovered that a red azo dye also had antibacterial properties. The resulting compound, Prontosil (also known as a sulfa drug because it contains sulfur) became the first widely used antibiotic.

Prontosil

In addition to aromatic nitrogen compounds, nitrogen can also be incorporated directly into cyclic structures forming a heterocycle. Recall that a heterocycle is any cyclic organic molecule that contains a heteroatom (typically N, S, or O). Heterocycles that contain nitrogen are widely found in nature and contribute to the biological activity of many compounds.

Many heterocyclic amines occur naturally in plants. Like other amines, these compounds are basic. Such a compound is called an alkaloid, a name that means “like alkalis.” Many alkaloids are physiologically active, including the familiar drugs caffeine, nicotine, and cocaine.

To Your Health: Three Well-Known Alkaloids

Caffeine is a stimulant found in coffee, tea, and some soft drinks. Its mechanism of action is not well understood, but it is thought to block the activity of adenosine, a heterocyclic base that acts as a neurotransmitter, a substance that carries messages across a tiny gap (synapse) from one nerve cell (neuron) to another cell. The effective dose of caffeine is about 200 mg, corresponding to about two cups of strong coffee or tea.

Nicotine acts as a stimulant by a different mechanism; it probably mimics the action of the neurotransmitter acetylcholine. People ingest this drug by smoking or chewing tobacco. Its stimulant effect seems transient, as this initial response is followed by depression. Nicotine is highly toxic to animals. It is especially deadly when injected; the lethal dose for a human is estimated to be about 50 mg. Nicotine has also been used in agriculture as a contact insecticide.

Cocaine acts as a stimulant by preventing nerve cells from taking up dopamine, another neurotransmitter, from the synapse. High levels of dopamine are therefore available to stimulate the pleasure centers of the brain. The enhancement of dopamine action is thought to be responsible for cocaine’s “high” and its addictive properties. After the binge, dopamine is depleted in less than an hour. This leaves the user in a pleasureless state and (often) craving more cocaine.

Cocaine is used as the salt cocaine hydrochloride and in the form of broken lumps of the free (unneutralized) base, which is called crack cocaine.

Because it is soluble in water, cocaine hydrochloride is readily absorbed through the watery mucous membranes of the nose when it is snorted. Crack cocaine is more volatile than cocaine hydrochloride. It vaporizes at the temperature of a burning cigarette. When smoked, cocaine reaches the brain in 15 seconds.

Summary

Amines are bases; they react with acids to form salts. Salts of aniline are properly named as anilinium compounds, but an older system is used to name drugs: the salts of amine drugs and hydrochloric acid are called “hydrochlorides.” Heterocyclic amines are cyclic compounds with one or more nitrogen atoms in the ring.

Concept Review Exercises

Explain the basicity of amines.
Contrast the physical properties of amines with those of alcohols and alkanes.
What is a heterocyclic compound?

Answers

Amines have a lone pair of electrons on the nitrogen atom and can thus act as proton acceptors (bases).
The solubilities of amines are similar to those of alcohols; the boiling points of primary and secondary amines are similar to those of alcohols; the boiling points of tertiary amines, which cannot engage in hydrogen bonding because they do not have a hydrogen atom on the nitrogen atom, are comparable to those of alkanes.
Heterocyclic compounds are ring compounds with atoms other than carbon atoms in the ring.

Exercises

What salt is formed in each reaction? Write its condensed structural formula.
1. CH₃NH₂(aq) + HBr(aq) →
2. CH₃NHCH₃(aq) + HNO₃(aq) →
What salt is formed in each reaction? Draw its structure.

Answer

1. CH₃NH₃⁺Br⁻(aq)
2. [CH₃NH₂CH₃]⁺NO₃⁻(aq)

Career Focus: Emergency Medical Technician (EMT)

Paramedics are highly trained experts at providing emergency medical treatment. Their critical duties often include rescue work and emergency medical procedures in a wide variety of settings, sometimes under extremely harsh and difficult conditions. Like other science-based professions, their work requires knowledge, ingenuity, and complex thinking, as well as a great deal of technical skill. The recommended courses for preparation in this field include anatomy, physiology, medical terminology, and—not surprisingly—chemistry. An understanding of basic principles of organic chemistry, for example, is useful when paramedics have to deal with such traumas as burns from fuel (hydrocarbons) or solvent (alcohols, ethers, esters, and so on) fires and alcohol and drug overdoses.

To become a paramedic requires 2–4 y of training and usually includes a stint as an emergency medical technician (EMT). An EMT provides basic care, can administer certain medications and treatments, such as oxygen for respiratory problems and epinephrine (adrenalin) for allergic reactions, and has some knowledge of common medical conditions. A paramedic, in contrast, must have extensive knowledge of common medical problems and be trained to administer a wide variety of emergency drugs.

Paramedics usually work under the direction of a medical doctor with a title such as “medical director.” Some paramedics are employed by fire departments and may work from a fire engine that carries medical equipment as well as fire-fighting gear. Some work from hospital-sponsored ambulances and contiAmidesnue to care for their patients after reaching the hospital emergency room. Still other paramedics work for a government department responsible for emergency health care in a specific geographical area. Finally, some work for private companies that contract to provide service for a government body.

An experienced paramedic has a broad range of employment options, including training for mountain or ocean rescue, working with police department special weapons and tactics (SWAT) teams, or working in isolated settings such as on oil rigs. With their expertise at treating and stabilizing patients before quickly moving them to a hospital, paramedics often provide the first critical steps in saving an endangered life. The following quotation, inscribed on the Arlington National Cemetery headstone of Army Lieutenant R. Adams Cowley, who is often called the “father” of shock trauma medicine, serves as the motto for many paramedic units: “Next to creating a life the finest thing a man can do is save one.” —Abraham Lincoln

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Amides

Structure and Physical Properties

The amide functional group has an nitrogen atom attached to a carbonyl carbon atom. If the two remaining bonds on the nitrogen atom are attached to hydrogen atoms, the compound is a simple amide. If one or both of the two remaining bonds on the atom are attached to alkyl or aryl groups, the compound is a substituted amide.

The carbonyl carbon-to-nitrogen bond is called an amide linkage. Under conditions of neutral pH, this bond is quite stable and is the primary functional group found in the repeating units of protein molecules, where it is called a peptide linkage. However, in acidic conditions, like those found in the stomach, the amide bond is hydrolized to form a carboxylic acid and amine.

Simple amides are named as derivatives of carboxylic acids. The –ic ending of the common name or the –oic ending of the IUPAC name of the carboxylic acid is replaced with the suffix –amide. For example, the amide version of formic acid is called formamide.

With the exception of formamide (HCONH₂), which is a liquid, all simple amides are solids (Table 10.1) The lower members of the series are soluble in water, with borderline solubility occurring in those that have five or six carbon atoms. Like the esters, solutions of amides in water usually are neutral—neither acidic nor basic.

Physical Constants of Some Unsubstituted Amides
Condensed Structural Formula	Name	Melting Point (°C)	Boiling Point (°C)	Solubility in Water
HCONH₂	formamide	2	193	soluble
CH₃CONH₂	acetamide	82	222	soluble
CH₃CH₂CONH₂	propionamide	81	213	soluble
CH₃CH₂CH₂CONH₂	butyramide	115	216	soluble
C₆H₅CONH₂	benzamide	132	290	slightly soluble

The amides generally have high boiling points and melting points. These characteristics and their solubility in water result from the polar nature of the amide group and hydrogen bonding (Figure 10.8) Similar hydrogen bonding plays a critical role in determining the structure and properties of proteins, deoxyribonucleic acid [DNA], ribonucleic acid [RNA], and other macromolecules so important to life processes. This will be discussed in further detail in Chapter 11.

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Figure 10.8 Hydrogen Bonding in Amides. Amide molecules can engage in hydrogen bonding with water molecules (a). Those amides with a hydrogen atom on the nitrogen atom can also engage in hydrogen bonding (b). Both hydrogen bonding networks extend in all directions.

Key Takeaways

Most amides are solids at room temperature; the boiling points of amides are much higher than those of alcohols of similar molar mass.
Amides of five or fewer carbon atoms are soluble in water?.

Concept Review Exercises

Which compound has the higher boiling point—pentanamide (CH₃CH₂CH₂CH₂CONH₂) or propyl acetate (CH₃COOCH₂CH₂CH₃)? Explain.
Which compound is more soluble in water—propanamide (CH₃CH₂CONH₂) or 1-pentene (CH₂=CHCH₂CH₂CH₃)? Explain.

Answers

pentanamide because the nitrogen-to-hydrogen (N–H) and the carbon-to-oxygen double (C=O) bonds can engage in hydrogen bonding; propyl acetate cannot engage in hydrogen bonding
propanamide because the N–H and C=O bonds can engage in hydrogen bonding with water; 1-pentene cannot engage in hydrogen bonding with water

More Practice

Which compound has the higher boiling point—butyramide (CH₃CH₂CH₂CONH₂) or ethyl acetate (CH₃COOCH₂CH₃)? Explain.
Which compound has the higher boiling point—butyramide or dimethylacetamide [CH₃CON(CH₃)₂]? Explain.
Which compound is more soluble in water—acetamide (CH₃CONH₂) or 1-butene (CH₂=CHCH₂CH₃)? Explain.
Which compound is more soluble in water—CH₃CONHCH₃ or 2-methylbutane [CH₃CH(CH₃)CH₂CH₃)]? Explain.

Answers

butyramide because the nitrogen-to-hydrogen (N–H) and the carbon-to-oxygen double (C=O) bonds can engage in hydrogen bonding; ethyl acetate cannot engage in hydrogen bonding

acetamide because the N–H and C=O bonds can engage in hydrogen bonding with water; 1-butene cannot engage in hydrogen bonding with water

Formation of Amides

Amides are formed by the addition of an amine to a carboxylic acid, and thus, resemble an ester in structure. Amide reactions occur very slowly in the laboratory at room temperature. Similar to ester formation, amide formation is a dehydration reaction where water molecules are split out, and a bond is formed between the nitrogen atom and the carbonyl carbon atom.

In living cells, amide formation is catalyzed by enzymes. Proteins are polyamides; they are formed by joining amino acids into long chains. In proteins, the amide functional group is called a peptide bond. The formation of proteins will be discussed in greater detail in Chapter 11.

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A Closer Look: Synthetic Polyamides

Many synthetic fabrics are polyamide structures, that is, they contain many amide bonds that link together smaller molecules that act as building blocks. Two important ones are nylon and Kevlar. This section looks at the structures, formation, and hydrolysis of these polyamides.

Polyamides are polymers where the repeating units are held together by amide links. An amide group has the formula – CONH₂. An amide link has this structure:

In nylon, the repeating units contain chains of carbon atoms. (That is different from Kevlar, where the repeating units contain benzene rings – see below.) There are various different types of nylon depending on the nature of the carbon chains.

Nylon-6,6 is made from two monomers each of which contain 6 carbon atoms – hence its name. One of the monomers is a 6 carbon acid with a -COOH group at each end – it is called hexadioic acid. The other monomer is a 6 carbon chain with an amino group, -NH₂, at each end. This is 1,6-hexadiamine.

10.9 Formation of Nylon-6,6.

When these two compounds polymerize, the amine and acid groups combine, each time with the loss of a molecule of water. This is known as condensation polymerization. Condensation polymerization is the formation of a polymer involving the loss of a small molecule. In this case, the molecule is water, but in other cases different small molecules might be lost. Note that this reaction does not readily occur at room temperature. To get amide formation, the reaction must be subjected to high heat (~350^oC) and high pressure conditions.

Figure 10.9 shows the loss of water between two of the monomers. As long as the reagents are readily available and conditions are favorable, condensation polymerization keeps on happening, and so you get a chain that alternates between the building block units and looks like this:

Kevlar is similar in structure to nylon-6,6 except that instead of the amide links joining chains of carbon atoms together, they join benzene rings. The two monomers are benzene-1,4-dicarboxylic acid and 1,4-diaminobenzene.

10.10 The Formation of Kevlar

Similar to nylon, the reactions of kevlar will continue to react and undergo condensation polymerization building long fibers.

Uses of polyamides

Nylon: Apart from obvious uses in textiles for clothing and carpets, a lot of nylon is used to make tire cords – the inner structure of a vehicle tire underneath the rubber. The fibers are also used in ropes, and nylon can be cast into solid shapes for cogs and bearings in machines, for example.
Figure 10.11 Examples of Nylon. (A) Nylon 6,6 produced in a laboratory experiment. Nylon used to make (B) rope, (C) umbrellas, and (D) rain jackets. Photo of Nylon 6,6 is provided by: University of Ulm, Photo of nylon rope provided by: Angelsharum, Photo of nylon jackets provided by: Sam Kim.
Kevlar: Kevlar is a very strong material – about five times as strong as steel, weight for weight. It is used in bulletproof vests, in composites for boat construction, in lightweight mountaineering ropes, and for lightweight skis and racquets – amongst many other things.
Figure 10.12 Examples of Kevlar. Kevlar used in (A) canoes, (B) bullet-proof vests, (C) knife-proof sleeves, and (D) workboots. Photo of canoe provided by: Franklin.vp, Photo of bullet-proof vest provided by: Cyril Thomas, Photo of kevlar sleeves provided by: Erin Carstens, and Photo of workboots provided by: Nextcrave

Key Takeaway

Amides are prepared by the reaction of a carboxylic acid with an amine.
Polyamides contain many amide bonds that link together smaller building blocks into a larger molecule.

Hydrolysis of Amides

Generally, amides resist hydrolysis in plain water, even after prolonged heating. In the presence of added acid or base, however, hydrolysis proceeds at a moderate rate. In living cells, amide hydrolysis is catalyzed by enzymes. Amide hydrolysis is illustrated in the following example:

Career Focus: Athletic Trainer

Athletic training is an allied health-care profession recognized by the American Medical Association. The athletic trainer’s role is to recognize, evaluate, and provide immediate care for athletic injuries; prevent athletic injuries by taping, bandaging, and bracing vulnerable body parts; make referrals to medical doctors when necessary; and rehabilitate injured athletes. Athletic trainers work in high schools, colleges, and other organizations where athletics programs are found. Athletic trainers usually have a degree from an accredited athletic training program whose curriculum includes such basic science courses as biology, chemistry, and physics. These studies provide the necessary background for more applied courses, such as anatomy and physiology, exercise physiology, kinesiology, and nutrition. Knowledge of chemistry is necessary for understanding pharmacological and medical terminology. For example, athletic trainers must understand the action of numerous drugs, many of which are esters, amines, or amides like those mentioned in this chapter.

Athletic trainers may have administrative duties, such as the responsibility for ordering supplies. They also need to be able to evaluate nutritional supplements because providing the wrong one can get an athlete banned from competition and may bring sanctions against a school. In short, the athletic trainer is responsible for the overall health and well-being of the athletes in his or her charge.

Key Takeaway

The hydrolysis of an amide produces a carboxylic acid and ammonia or an amine.

Exercises

Complete each equation.
Complete each equation.

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10.4 Chapter Summary

To ensure that you understand the material in this chapter, you should review the meanings of the following bold terms in the summary and ask yourself how they relate to the topics in the chapter. A carboxylic acid (R-COOH) contains the functional group COOH, called the carboxyl group, which has an OH group attached to a carbonyl carbon atom. An ester (R-COOR′) has an OR′ group attached to a carbonyl carbon atom. Sulfur can be incorporated into organic molecules as thiols (R-SH), disulfides (R-S-S-R’), thioethers (R-S-R’) or thioesters (R-COSR’). Phosphorus can be incorporated into organic molecules as phosphoesters (R-OPO₃^2-) (An amine is derived from ammonia (NH₃), with one, two, or all three of the hydrogen atoms of NH₃ replaced by an alkyl (or an aryl) group. The amide (RCONR’) functional group has a carbonyl group joined to a nitrogen atom from NH₃ or an amine.

Since sulfur is in the same family at oxygen, it has similar characteristics and reactivity when forming organic molecules. However, sulfur is not as electronegative as oxygen, thus, intermolecular forces between sulfur-containing molecules is similar but weaker than those containing oxygen. Thiols resemble the alcohol functional group and can undergo oxidation with other thiols to form disulfide bonds. Disulfide bonds are important in many biological molecules, such as proteins where they aid in maintaining the 3-dimensional structure of the molecules.

Amines are nitrogen-containing organic molecules derived from ammonia (NH₃). A primary (1°) amine (RNH₂) has one organic group bonded to the nitrogen atom, a secondary (2°) amine (R₂NH) has two organic groups bonded to the nitrogen atom, and a tertiary (3°) amine (R₃N) has three organic groups bonded to the nitrogen atom. Amines are basic compounds that react with strong acids to produce ammonium (NH₄⁺) salts. A cyclic compound in which the ring contains one or more noncarbon atoms is called a heterocyclic compound. There are many heterocyclic amines, including many physiologically important ones. Alkaloids are heterocyclic amines found in many plants. Caffeine, nicotine, and cocaine are familiar alkaloids.

The formation of esters and the related compounds, thioesters, amides, and phosphoesters are formed by dehydration synthesis, involving the loss of water. Some of the most important esters in biochemistry are those formed from phosphoric acid. The structures of DNA and RNA contain phosphodiester linkages.

Most amides are colorless and odorless, and the lighter ones are soluble in water. Because they are polar molecules, amides have comparatively high boiling points and melting points. Amides are synthesized from carboxylic acids and NH₃ or amines. Amides are neutral compounds. They resist hydrolysis in water, but acids, bases, and enzymes catalyze the breakdown reaction.

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10.5 References

Sulfur mustard. (2017, May 11). In Wikipedia, The Free Encyclopedia. Retrieved 00:30, May 16, 2017, from https://en.wikipedia.org/w/index.php?title=Sulfur_mustard&oldid=779831530
Nitrogen mustard. (2017, May 10). In Wikipedia, The Free Encyclopedia. Retrieved 00:31, May 16, 2017, from https://en.wikipedia.org/w/index.php?title=Nitrogen_mustard&oldid=77970721.
Sarin. (2017, May 9). In Wikipedia, The Free Encyclopedia. Retrieved 00:31, May 16, 2017, from https://en.wikipedia.org/w/index.php?title=Sarin&oldid=779604274
Ethanethiol. (2017, February 21). In Wikipedia, The Free Encyclopedia. Retrieved 01:44, May 16, 2017, from https://en.wikipedia.org/w/index.php?title=Ethanethiol&oldid=766730923
Disulfide. (2017, May 15). In Wikipedia, The Free Encyclopedia. Retrieved 02:06, May 16, 2017, from https://en.wikipedia.org/w/index.php?title=Disulfide&oldid=780480973
Ophardt, C. (2013) Biological Chemistry. Libretexts. Available at: https://chem.libretexts.org/Core/Biological_Chemistry/Proteins/Case_Studies%3A_Proteins/Permanent_Hair_Wave
Soderberg, T. (2016) Organic Chemistry with a Biological Emphasis. Libretexts. Available at: https://chem.libretexts.org/Textbook_Maps/Organic_Chemistry_Textbook_Maps/Map%3A_Organic_Chemistry_with_a_Biological_Emphasis_(Soderberg)
Ball, et al. (2016) MAP: The Basics of General, Organic, and Biological Chemistry. Libretexts. Available at: https://chem.libretexts.org/Textbook_Maps/Introductory_Chemistry_Textbook_Maps/Map%3A_The_Basics_of_GOB_Chemistry_(Ball_et_al.)
Aniline. (2017, April 11). In Wikipedia, The Free Encyclopedia. Retrieved 14:01, May 17, 2017, from https://en.wikipedia.org/w/index.php?title=Aniline&oldid=774896013
Clark, J. (2017) Organic Chemistry. Libretexts. Available at: https://chem.libretexts.org/Core/Organic_Chemistry/Amides/Reactivity_of_Amides/Polyamides

CH105: Consumer Chemistry

Chapter 10 – Compounds with Sulfur, Phosphorus, and Nitrogen

Opening Essay – Organic Chemicals as Agents of War

Mustard Gas

Development of the first chemotherapy drug

Organophosphate Nerve Agents

10.1 Compounds Containing Sulfur

Thiols and Disulfides

Thioethers

Thioesters

Key Takeaway

Answers

More Practice

Answers

A Closer Look: Synthetic Polyamides

Uses of polyamides

Key Takeaway

Hydrolysis of Amides

Career Focus: Athletic Trainer

Key Takeaway

Exercises

10.5 References

Tools

Resources