Volume 4

Amines. Basicity of Amines • Aniline • Amino Acids. Proteins • Chirality. We Are All Chiral! • Nylon. Kevlar®. Nomex® • Exercises
4.9.1. Amines. Basicity of Amines. Amines are organic derivatives of ammonia, NH3. Replacement of one, two, or all three hydrogen atoms on the molecule of NH3 with an organic group produces amines. Some examples of amines are presented in Figure 4-144.
Figure 4-144. Examples of amines with names.

The way amines are named should be pretty clear from Figure 4-144. Amines bearing one, two, and three organic groups are called primary, secondary, and tertiary amines, respectively. To name a primary amine, name the organic group on the N atom, followed by "amine", in one word. If both substituents on the N atom of a secondary amine are identical, place prefix "di" before the name of the organic group, followed by "amine". If the groups are different, name each of them before "amine". Tertiary amines with three identical groups are named using prefix "tri". If only two groups are identical, name them with prefix "di", followed by the name of the group, then name the third group before saying or writing "amine". If all three groups are different, name each of them, followed by "amine". Although phenylamine is a correct name for the simplest aromatic amine, it is conventionally called by its common name, aniline.

Most amines are liquids, although the simplest amine, methylamine (CH3NH2) is a gas at room temperature and atmospheric pressure. There are also some solid amines, for instance hexamethylenetetramine (Figure 4-145), also known as hexamine. Hexamine is sold in stores as smokeless solid fuel tablets for camping and other outdoor uses. The tablets burn very cleanly and are safe to handle. Hexamethylenetetramine has a very faint ammonia-like smell, in contrast with most other amines that have a strong rotten fish odor.
Figure 4-145. Hexamethylenetetramine.

Like hexamethylenetetramine, other amines burn in air to give CO2, H2O, and N2. A balanced chemical equation for the combustion of methylamine is presented below.

4 CH3NH2 + 9 O2 = 4 CO2 + 10 H2O + 2 N2

Write balanced chemical equations for the combustion of triethylamine, aniline, and hexamethylenetetramine.

Ammonia is a base. The basicity of ammonia comes from the lone electron pair on the nitrogen atom. This electron pair is responsible for the formation of the coordinate bond between a molecule of ammonia and a proton. Amines are also bases behaving in exactly the same way (Figure 4-146).
Figure 4-146. Protonation of ammonia and methylamine.

Some amines are more basic than ammonia and some are less. While aniline and other aromatic amines are weaker bases than NH3, alkyl amines are more basic than ammonia. For example, methylamine is over 10 times stronger a base than ammonia. Dimethylamine is slightly more basic than methylamine. Trimethylamine, however, is less basic than methylamine and dimethylamine, while still being more basic than NH3. The order of basicity is as follows.

(CH3)2NH > CH3NH2 > (CH3)3N > NH3 > C6H5NH2

Similarly to solutions of ammonia in water, aqueous solutions of alkyl amines change the color of red litmus paper to blue and turn purple-pink on addition of phenolphthalein, thereby indicating the presence of hydroxide. The OH- comes from the reversible abstraction of a proton from H2O molecules by ammonia or an amine (Figure 4-147). To name a cation produced on protonation of an amine, just add the name of the organic substituent before "ammonium". The cation shown at the bottom in Figures 4-146 and 4-147 is methylammonium. Protonation of dimethylamine, methylethylamine, and triethylamine produces dimethylammonium, methylethylammonium, and triethylammonium ions, respectively.
Figure 4-147. Reversible deprotonation of water with ammonia (top) and with methylamine (bottom).

4.9.2. Aniline. As mentioned above, aniline and other aromatic amines are weaker bases than NH3. Aqueous solutions of aniline (solubility ~3.5 g in 100 mL at 20 oC) are not basic enough to change the color of red litmus paper. Nevertheless, aniline forms salts with strong acids, such as H2SO4 and HCl. Adding concentrated HCl to aniline results in the formation of white crystals of phenylammonium (anilinium) chloride (Figure 4-148).
Figure 4-148. Reaction of aniline with HCl.

Aniline is an oily liquid with a boiling point of 184 oC. Pure aniline is colorless, but on storage it turns yellow due to slow oxidation with the air. Aniline is toxic. The synthesis of aniline was discovered by Nikolai Zinin (1812-1880), an outstanding Russian chemist who demonstrated that aniline can be prepared by the reduction of nitrobenzene. In his work, Zinin used hydrogen sulfide to reduce nitrobenzene to aniline.

C6H5NO2 + 3 H2S = C6H5NH2 + 3 S + 2 H2O

The first samples of aniline prepared by Zinin himself about 175 years ago are on display in The Museum of Kazan School of Chemistry, Kazan, Russia (Figure 1-149).
Figure 4-149. Nikolai Zinin (1812-1880) (source) and original samples of aniline prepared and flame-sealed in glass tubes by Zinin (source).

We put special emphasis on Zinin's synthesis of aniline because of the exceptional importance of this reaction. In their obituary on Nikolai Zinin, the two outstanding German chemists, August Wilhelm von Hofmann (1818-1892) and Johann Karl Wilhelm Ferdinand Tiemann (1848-1899), wrote:

"If Zinin had done nothing more than to convert nitrobenzene into aniline, even then his name should be inscribed in golden letters in the history of chemistry!" ("Hätte Zinin nichts Anderes als die Ueberführung des Nitro- benzols in Anilin gelehrt, sein Name würde mit goldenen Lettern in der Geschichte der Chemie verzeichnet bleibeu!").

The importance of aniline stems from many factors. One is that, being readily and cheaply available, aniline displays a very rich chemistry. Also, without aniline there would have been no modern synthetic dyes. Although most of the currently produced aniline is used to make polyurethanes, the dye industry also consumes large amounts of aniline. One important pigment produced from aniline is indigo (Figure 4-150), which is used to dye denim for the production of blue jeans.
Figure 4-150. Structure of indigo with the aniline moiety in blue (left) and bulk samples of indigo (right; source).

In the modern industry, the reduction of nitrobenzene to aniline is performed with hydrogen in the presence of a catalyst (Figure 4-151). This method is much environmentally cleaner and vastly more economical than the reduction with H2S, originally developed by Zinin.
Figure 4-151. Catalytic reduction of nitrobenzene to aniline with H2.
Digression. The first synthetic aniline dye was discovered by accident. In 1856, William Henry Perkin (1838-1907), the then 18-year-old youngest of the seven children of a carpenter, was doing research in his home laboratory in the East End of London. In one experiment, he oxidized aniline with potassium dichromate, K2Cr2O7, and obtained a black solid. When cleaning the reaction flask with ethanol, Perkin noticed the remarkable purple color of the ethanol extract. Perkin isolated the purple substance, which he called "mauveine". Having found that his mauveine died silk and that the color was both beautiful and stable, Perkin applied for a patent and started to manufacture the dye. Back then, all dyes to color fabrics were extracted from natural sources. The natural purple dye Tyrian or Royal Purple, which was in great demand from the wealthy aristocracy, was obtained from some sea mollusks in a particularly tricky, labor-intense, and costly procedure. Perkin's mauveine emerged as a vastly lower-cost, higher-quality replacement for Tyrian Purple to become the first commercial synthetic color, thereby marking the birth of the synthetic dye industry.
4.9.3. Amino Acids. Proteins. Amino acids are organic compounds bearing both an amino group NH2 and a carboxy group COOH on the same molecule. The simplest amino acid is aminoacetic acid, H2N-CH2-COOH, also known as glycine. While many amino acids have common names, they can also be named by naming the parent acid prefixed by the number of the carbon atom the NH2 group is bonded to, followed by "amino" (Figure 4-152).
Figure 4-152. Examples of amino acids with names.

Amino acids are white crystalline compounds. A remarkable feature of amino acids is the presence on their molecules of two different functional groups, one of which is basic (amine) and the other acidic (carboxy). Consequently, amino acids react with both acids and bases (Figure 4-153). Bases neutralize the COOH group, whereas acids protonate the NH2 group. Since amino acids react with both acids and bases, they may be viewed as amphoteric organic compounds.
Figure 4-153. Reactions of aminoacetic acid (glycine) with NaOH (top) and HCl (bottom).

In the absence of strong acids or bases, amino acids neutralize themselves internally by means of reversible proton transfer from the acidic carboxyl group to the basic amino group (Figure 4-154). The result of this transfer is an inner salt, a chemical compound bearing a cationic center and an anionic center within the same molecule. Inner salts are also often called zwitterions from German Zwitter = hermaphrodite.
Figure 4-154. Intramolecular "self-neutralization" of an amino acid.

The COOH group of an amino acid can react with the NH2 group of another molecule of the same or different amino acid. As a result, a dipeptide is formed, in which the two amino acid residues are connected by an amido or peptide bond, C(O)-NH (Figure 4-155).
Figure 4-155. Formation of a dipeptide from two molecules of aminoacetic acid.

Similarly, the amino group or the COOH group of the dipeptide formed can react with yet another amino acid molecule, then with one more, and so on. As a result, a polymer is produced, which is called a polypeptide or just peptide.

We have already learned that carbohydrates can dimerize and polymerize. Molecules of glucose are the building blocks used by nature to make starch, a polymer that is the source of energy for animals and plants. Similarly, amino acids are polymerized in living organisms to make special polypeptides that are called proteins. Proteins are the materials the tissues of our bodies are made of. Various proteins are used in nature to make muscles, cartilage, hair, blood vessels, and other tissues. In both plants and animals, proteins are involved in a myriad of functions, without which life would be impossible.

Every protein is a polypeptide but not every polypeptide is a protein. Proteins are polymers of a finite number of particular amino acids that are called proteinogenic amino acids. There are 22 amino acids used by living organisms to build proteins, all of them being 2-aminoacids. Of these 22, we, humans, use 20. Of these 20, our body can synthesize 12. The other 8, called essential amino acids, have to come from the food that we eat in order to avoid malnutrition.

Proteins are made of hundreds of amino acid residues. Considering the number of the amino acid building blocks (20) in various ratios and sequences, the number of different proteins is virtually unlimited. As each of us needs our own specific set of proteins, our bodies cannot use proteins that we consume in foods. Our bodies first need to hydrolytically depolymerize the external proteins to individual amino acids and then use them, along with our own-produced amino acids to build the unique set of proteins each of us needs.
Digression. It is often said that vegetarians cannot be healthy and that their brain cannot function properly because some of the essential amino acids can come only from animal products such as red meat, poultry or fish. Is that true? Click here to make your own judgement. Apparently all necessary amino acids can be obtained from plants and even a 100% vegan diet can be sufficiently healthy, let alone an ovo-lacto vegetarian one.
4.9.4. Chirality. We Are All Chiral! Figure 4-156 displays two 3-D structures (using wedge and dash notation) of alanine, one of the simplest and smallest amino acids. Are these two structures 100% identical?
Figure 4-156. Structure of alanine showing the tetrahedral geometry of the central carbon atom.

Here is an answer to this question. The two structures in Figure 4-156 are as mutually identical as one of our hands is identical with the other one. We often think that our left hand is the same as the right hand. Yet if we try to superimpose them, we quickly find out that this is impossible. One of the two hands is a mirror image of the other. Likewise, the structures shown in Figure 4-156 are mirror reflections of each other. They are the same and yet not exactly the same because they are not superimposable. Figure 4-157 further illustrates this point. We are now dealing with a type of isomerism that is new to us. This isomerism is called enantiomerism. The two isomers of alanine shown in Figures 4-156 and 4-157 are enantiomers.
Figure 4-157. Enantiomers of alanine as mirror images of each other.

All 20 amino acids that our body needs are 2-amino acids, the number meaning that the NH2 substituent in their molecules is located on the carbon atom next to the COOH group. The general formula of 2-aimno acids is therefore R-CH(NH2)COOH. For glycine and alanine, R = H and CH3, respectively. For valine, R = isopropyl, (CH3)2CH (Figure 4-152). Except for one (see below), all 2-amino acids can exist in two enantiomeric forms, as illustrated by Figure 4-158.
Figure 4-158. Enantiomers of 2-amino acids (source).

A molecule that is not superimposable with its mirror image is called a chiral molecule, from Greek χέρι (hand), which certainly makes sense (Figure 4-158). All organic compounds containing a tetrahedral (sp3) carbon atom bearing four different substituents are chiral. A carbon atom bonded to four different atoms or groups of atoms is referred to as a chiral carbon atom, or a chiral center, or a center of chirality.

Among the 20 amino acids found in our bodies, there is only one that is non-chiral, glycine (R = H). Of the four substituents on the sp3 carbon of glycine, two are identical (H atoms), exactly what makes glycine non-chiral. Imagine R = H in Figure 4-158 and you will see that the two images become superimposable.

As we have already learned, carbon skeleton isomers, substituent position isomers, double or triple bond position isomers, and cis-trans isomers all display different physical properties, such as boiling and melting points, density, and more. This is not the case with enantiomers. All physical properties of enantiomers are identical, except just one: enantiomers rotate plane-polarized light by the same angle, but in opposite directions. That is why enantiomers are sometimes called optical isomers. Enantiomers that rotate plane-polarized light to the right are called dextrorotatory from Latin "dexter", meaning right, and are designated as D. The ones rotating plane-polarized light to the left are called laevorotatory (or levorotatory) from Latin "laevus", meaning left, and are designated as L (see, for example, Figure 4-159).
Figure 4-159. Structures of D-alanine and L-alanine.

As structurally insignificant as the difference between two given enantiomers might seem, that difference is of extreme importance. Life on Earth is based on proteins composed of L-enantiomers of amino acids. D-amino acids are seldom found in nature. The rare case of some bacteria using D-enantiomers of amino acids is the exception that proves the rule: leftists and rightists, Christian, Muslim, Jews, and Buddhists, atheists and agnostics, all of us are made up of levorotatory amino acids, no exception.

Why L-, not D-amino acids? Expect to win a Nobel Prize and become super-famous and rich if you can answer this question.

4.9.5. Nylon. Kevlar®. Nomex®. All of us have seen spider silk, but did you know that, "Quantitatively, spider silk is five times stronger than steel of the same diameter. It has been suggested that a Boeing 747 could be stopped in flight by a single pencil-width strand and spider silk is almost as strong as Kevlar, the toughest man-made polymer" (source)? Believe it or not, spider silk, which is stronger than steel, is a protein fiber, an organic polymer made of amino acids. There are chemically akin man-made polymers that are even more than 5 times stronger than steel, such as certain types of Kevlar®. First, however, let us consider nylon, a polymer of exceptional importance.

One type of nylon is a polymer of 6-aminohexanoic acid. Polycondensation of this amino acid occurs due to the formation of the C(O)-N(H) bond between its molecules via extrusion of molecules of water. After the formation of the first C(O)-N(H) bond, the resultant dimer reacts with another monomer molecule and so on (Figure 4-160). The resultant polymer is called nylon 6 to indicate the number of carbon atoms in the monomer, 6-aminohexanoic acid.
Figure 4-160. Polycondensation of 6-aminohexanoic acid to Nylon 6.

As a matter of fact, it is not pre-formed and isolated 6-aminohexanoic acid that is used in the synthesis of nylon 6, but its precursor called caprolactam (Figure 4-161). Caprolactam is made from cyclohexane via a series of beautiful chemical transformations that are, alas, beyond the scope of our course.
Figure 4-161. Formation of Nylon 6 from caprolactam.

Interestingly, water is used in catalytic rather than stoichiometric quantities to make nylon 6 from caprolactam. Think this way: one molecule of water is consumed to ring-open one molecule of caprolactam by hydrolysis of its amide bond. When the 6-aminohexanoic acid produced reacts with another molecule of 6-aminohexanoic acid formed in the same way, one molecule of water is released. This molecule of water then gets involved in the ring-opening of another molecule of caprolactam. The process repeats itself again and again until the polymerization reaction has gone to completion.

Nylon 6 is largely produced in Europe. In North America, a different type of nylon is manufactured and used, nylon 6.6. Nylon 6.6 is made from two monomers. One of the two is hexamethylenediamine, whose molecule contains two amino groups, and the other is adipic acid (Figure 4-162). Both the diamine and diacid monomers contain 6 carbon atoms, hence the name nylon 6.6.
Figure 4-162. Polycondensation of adipic acid with hexamethylenediamine to Nylon 6.6.
Digression. Nylon 6.6 was invented first. The inventor, a brilliant American chemist Wallace Carothers (1896-1937) made the first samples of nylon 6.6 in 1935, when working for the DuPont Company. This groundbreaking discovery prompted the development of nylon 6 in Germany 3 years later. Originally, nylon was intended to be used for making toothbrushes, which before 1938 were made with bore and horse bristle. In 1938, first nylon toothbrushes entered the market. Sadly, Carothers took his own life in 1937 as a result of deep depression, and could not witness the triumph of his invention. And the triumph was incredible indeed. The next application of nylon was in nylon fiber stockings, which conquered the market immediately after their first appearance for sale in 1939-1940. A pair of "nylons" was sold for $1.15 back in 1940, when the median weekly income for American men and women was $18.50 and $11.50, respectively. The nylon stocking craze – yes, it was a real craze – abruptly came to an end when the U.S.A. declared war on Japan the day after the devastating attack of the Japanese air forces on the U.S. naval base in Pearl Harbor on December 7, 1941. The American government ordered all nylon to be used only for military needs. After the war was over, DuPont resumed the production of nylon stockings to the delight of American women. However, the supply failed to meet the exceedingly high demand, even though the nylon plants operated at full capacity. The unmet demand prompted the nylon riots. In 1945, one month before Christmas, queues to the department stores having nylons in stock consisted of tens of thousands of shoppers, up to 30,000 women in New York City and 40,000 women in Pittsburgh. The lucky ones would sometimes put on their just purchased nylons right in the street, while receiving the envious looks from those still in the mile-long line (Figure 4-163). The demand for nylon stockings was finally met in 1946.
Figure 4-163. An American woman putting on just purchased nylons in the street (1945) (source). Note the queue in the background.

Besides fibers for stockings, fabrics, carpets, and ropes, nylon finds numerous other applications, including for food packaging and in the automobile industry for tires and various molded parts, especially in the engine compartment. Nylon guitar strings have gained tremendous popularity since their development with an active participation of the classical guitar virtuoso Andrés Segovia.

Close relatives of nylon 6.6 are Kevlar® and Nomex®. Both are made from aromatic monomers (Figure 4-164). Kevlar® is an exceptionally high-strength material that was originally famous for its use in bulletproof vests and racing bicycle tires but now has many more applications. Kevlar is 5-7 times stronger than steel. Nomex® is renowned for its resistance to heat, which makes it indispensable in the production of special fabrics for firefighters, military air crew, and race car drivers, among other applications.
Figure 4-164. Structures of Kevlar® and Nomex®.

A brief remark is due concerning the terminology used for the C(O)-NH bond. This bond is sometimes called a peptide bond and sometimes an amide bond. Both names are correct. For a biochemist dealing with proteins, the C(O)-NH bond is a peptide bond. Polymer chemists call this bond an amide bond. Polymers based on the amide bond are called polyamides. Both types of nylon, Kevlar®, and Nomex® are polyamides.

4.9.6. Exercises.

1. Draw chemical structures of (a) pentylamine; (b) dimethylbutylamine; (c) methylethylammonium chloride; (d) aniline; (e) phenylammonium bromide; (f) 3-aminopentanoic acid; (g) 2-methyl-3-aminobutanoic acid.

2. Are ethylamine, diethylamine, and triethylamine stronger bases than ammonia? Answer

3. Place ammonia, trimethylamine, dimethylamine, methylamine, and aniline in the order of decreasing basicity. Answer

4. Write a balanced chemical equation for the full combustion of propylamine. Answer

5. You have benzene, nitric acid, sulfuric acid, and sodium sulfide. How can aniline be made using these chemicals? Answer

6. Which of the following compounds are chiral? (a) dichlorobromomethane; (b) 3-aminobutanoic acid; (c) 4-aminobutanoic acid; (d) bromochlorofluoroiodomethane; (e) bromochlorofluoromethane; (f) isopropanol; (g) acetone; (h) 3-methylhexane; (i) 3-methyl-1-pentene. Hint

7. For each chiral compound identified in Exercise 6 above, sketch 3-dimensional structures of both enantiomers using wedge and dash notation to illustrate that one is a mirror image of the other.

8. Draw a chemical scheme for the formation of the alanine inner salt (zwitterion) from alanine. Hint

9. Write chemical equations for reactions of alanine with (a) HBr and (b) KOH. Hint

10. Draw chemical formulas for nylon 6.6 and nylon 6 and schemes for their formation from the corresponding monomers. [Answer: Figures 4-161 and 4-162]

11. Explain why catalytic rather than stoichiometric amounts of water are used to make nylon 6 from caprolactam. Answer

12. Review the structures of Kevlar® and Nomex® (Figure 4-164) and figure out what monomers are used to make both polyamides. Draw the structures of, and provide chemical names for, the monomers.