Volume 4

Glucose, Fructose, and Sucrose • Cellulose and Starch • Exercises
4.8.1. Glucose, Fructose, and Sucrose. We all have heard the word "carbohydrates" or just "carbs" many times. Carbohydrates constitute one of the three main macronutrients, the other two being fats and proteins. Although the "carbs" have received a bad reputation in certain countries, they are essential for our well-being and health, providing the energy that is critical for the proper functioning of our bodies, especially of the brain and muscles.

Carbohydrates are conventionally referred to as sugars or saccharides. The old name "carbohydrate", meaning "hydrated" or "watered" carbon, comes from the fact that all saccharides known back then fitted the general formula Cn(H2O)m. For example, the formula of sucrose, C12H22O11, may be rewritten as C12(H2O)11, formally a total of 12 carbon atoms "hydrated" with 11 molecules of water. Glucose and fructose are isomers having the same formula C6H12O6, or C6(H2O)6. Later on, sugars were found that did not fit the general formula Cn(H2O)m, such as deoxyribose (C5H10O4), a key component of DNA.

In this course, we will consider glucose, fructose, and sucrose as well as some of their simple derivatives. All three of these carbohydrates are sweet but have a different degree of sweetness, for which sucrose (table sugar) is used as the reference standard. Most humans can recognize sweetness in 1-2% solution of sucrose in water. Glucose is about 20-25% less sweet than sucrose, whereas fructose, the sweetest carbohydrate, is approximately 20-75% sweeter than sucrose. Some believe that there is nothing sweeter than fructose. That is not true. There are many compounds that are hundreds and even thousands of times sweeter. The most powerful sweetener, lugduname, is approximately 300,000 times as sweet as table sugar!

Glucose and fructose (Figure 4-129) are isomeric six-carbon-atom molecules featuring five OH groups and either an aldehyde (glucose) or a ketone (fructose) group. A carbohydrate containing an aldehyde group is referred to as an aldose and that bearing a ketone group a ketose.
Figure 4-129. Glucose and fructose.

One would have thought that glucose and fructose could be experimentally distinguished using the Cu(OH)2 or the silver mirror test, which are characteristic of aldehydes but not of ketones (4.7.3). However, this is not the case. Under the alkaline conditions that are invariably used for both tests, fructose isomerizes to glucose as well as to mannose, which is also an aldose. These two aldoses, produced under the alkaline conditions of the tests, give a positive reaction for aldehydes.

Oxidation of the aldehyde group of glucose gives rise to gluconic acid (Figure 4-130). In industry, gluconic acid is produced by microbal oxidation of glucose. Some salts of gluconic acid find important uses. Calcium gluconate is used to treat calcium deficiency in blood, as well as extremely painful and slowly healing hydrofluoric acid burns. Low blood levels of potassium are treated with potassium gluconate. Sodium gluconate also has many applications, including in the dyeing of textiles and as a cleaning agent for glass bottles and steel surfaces.
4-130. Oxidation of glucose to gluconic acid.

The aldehyde group of glucose can also be reduced to give sorbitol (Figure 4-131). In industry, this reduction is performed with hydrogen gas in the presence of a catalyst. Being only about 40% less sweet than table sugar, sorbitol is used as a low-calorie sweetener for sugar-free chewing gum and mints, diet foods, and cough syrups. Sorbitol is also a component of some toothpastes, mouthwash products, and moisturizing creams.
Figure 4-131. Reduction of glucose to sorbitol.

The structure of glucose shown in Figure 4-129 is the so-called linear form of glucose. In solution, this form is present only in small quantities, less than 0.5%. The rest are mainly two cyclic forms of glucose, α-glucose and β-glucose in a roughly 1:2 ratio, which exist in equilibrium with the linear form (Figure 4-132).
Figure 4-132. Equilibrium between the linear and cyclic forms of glucose.

Do not be intimidated by these cyclic structures. Let us figure out how this cyclization reaction occurs. The flexible carbon chain of glucose bends in such a way that the OH group in the 5 position can interact with the aldehyde group (Figure 4-133). This interaction (blue dotted lines) leads to the addition of the H atom of the OH group to the O atom of the aldehyde group and of the O atom of the OH group to the C atom of the aldehyde group. Compare the cyclic structure on the right of Figure 4-133 with those in Figure 4-132 and watch this animated cartoon to see how the cyclization happens.
Figure 4-133. The bending of the linear form of glucose leading to cyclization.

So, if over 99.5% of glucose in solution is in the cyclic forms, how come it undergoes the silver mirror reaction so efficiently? We know that this reaction is characteristic of aldehydes, but the cyclic forms of glucose are devoid of the aldehyde group. Maybe only the linear form of glucose is converted to gluconic acid and the cyclic forms stay intact in the presence of Ag+? No, this is not the case. Glucose reacts with Tollens' reagent in its entirety. That is because the linear and cyclic forms of glucose are in equilibrium and this equilibrium is fast. In accordance with Le Chatelier's principle, the equilibrium between the cyclic forms and the linear form shifts to the latter as it is consumed in the irreversible oxidation.

Two important reactions of glucose (as well as some other carbohydrates) are alcoholic and lactic acid fermentation (Figure 4-134). Alcoholic fermentation, also known as ethanol fermentation, converts a molecule of glucose to two molecules of ethanol and two molecules of CO2. In lactic acid fermentation, two molecules of lactic acid are produced from each molecule of glucose. Both types of glucose fermentation can be caused by various microorganisms such as bacteria and yeasts. With the right microorganism used, one or the other reaction can be performed selectively.
Figure 4-134. Alcoholic and lactic acid fermentation reactions of glucose.

Ethanol fermentation is used to make wines and other alcoholic beverages. Lactic acid fermentation is crucial in the manufacturing of various dairy products such as yogurt, butter milk, cheese, and sour cream. It is lactic acid that is responsible for the sour taste of these products.

Fructose, C6H12O6, is a ketose (ketone carbohydrate) and an isomer of glucose (Figure 4-129). Like glucose, fructose exists largely in its cyclic rather than linear form. The cyclization of fructose is also reversible, occurring through the addition of the OH group on the carbon atom in the 5th position to the C=O group (Figure 4-135).
Figure 4-135. Cyclization of the linear form of fructose.

Sucrose (table sugar or just sugar) is a disaccharide composed of glucose and fructose. Sucrose is conventionally extracted from sugarcane and sugar beets. In boiling water, sucrose is hydrolyzed to glucose and fructose (Figure 4-136). The resultant 1:1 mixture of glucose and fructose is called inverted (or invert) sugar. Being sweeter than regular table sugar, invert sugar is used in food industry.
Figure 4-136. Hydrolysis of sucrose (sugar) to glucose and fructose.

The hydrolysis of sucrose in pure water is rather slow, but can be efficiently catalyzed by small quantities of acids, such as HCl and H2SO4. To produce food grade invert sugar and invert sugar syrups, citric acid or lemon juice (contains ~5% citric acid) can be used. Industrial methods to make invert sugar from sucrose often employ an enzyme catalyst, invertase.
Digression. Like most other organic compounds, carbohydrates are combustible. However, if you try to set on fire a sugar cube, you will soon find out that the sugar melts but does not burn. Then take another sugar cube, sprinkle it with ashes and try again. It will burn. This is an old, very well-known demonstration experiment that you can watch here. Numerous articles and books say that the ashes catalyze the combustion of sugar. Moreover, some of these books and articles even state that the catalytic effect is due to potassium salts present in ashes and/or the alkaline nature of ashes. This view is still widely accepted, despite the fact that more than 40 years ago a note was published, seriously contesting the "catalytic" combustion explanation. In this publication, Douglas D. Smith of Guilford High School in Rockford, Illinois, wrote the following.

"A wide range of powdered solids, other than cigarette ashes, may be used to produce a burning sugar cube. Among these are powdered Al, Sb, Zn, Fe2O3, PbO, MnO2, graphite, talcum, instant coffee, nutmeg, cinnamon, and dirt. The effectiveness of such a wide variety of substances suggests that unquestioning application of the catchall explanation 'catalysis' may not be justified. Rather, the demonstration seems to illustrate the effect of particle size on the rate of combustion. The heat probably melts a thin film of sugar which then coats the particles. The kindling temperature of the film of sugar is reached before the melting process can dissipate the heat; hence, the rapid burning of the treated cube."

Indeed, as shown in this video, finely ground sucrose (icing sugar) is highly flammable when dispersed in air in the absence of any ashes or other additives. This story teaches us that, first, not everything that is written in books and articles is guaranteed to be 100% true, and, second, that stereotypes and even urban legends can be amazingly persistent even in science.
4.8.2. Cellulose and Starch. Both cellulose and starch are polymers of glucose and both are widespread in nature. In fact, cellulose is probably the most abundant organic compound on earth.

Starch is made by plants to store energy. Potatoes contain up to 20% starch, corn up to 70%, and rice up to 80%. Starch is one of the key nutrients.

Cellulose is produced by plants to build cell walls, the skeleton of the plant. Cellulose can be found in nature in a highly pure form. Cotton is up to 98% pure cellulose. Wood contains 40-50% cellulose. The importance of cellulose and starch in our everyday life is hard to overestimate.

Both starch and cellulose are white solids that are insoluble in water and other liquids. Fine starch powders can be solubilized in hot water though, to give cloudy, opalescent colloidal solutions. Concentrated colloidal solutions of starch are widely used as a nontoxic, environmentally friendly glue for paper and cardboard as well as for yarn crafts. Corrugated cardboard is made using a starch-based glue.

Cellulose and starch come from plants. First, plants make glucose and oxygen from water and carbon dioxide in the atmosphere, using the unique light-promoted reaction called photosynthesis.

6 CO2 + 6 H2O = C6H12O6 + 6 O2

The glucose produced in photosynthesis is then polymerized by plants to starch and cellulose.

Cellulose is a linear polymer of β-glucose (Figure 4-137). The construction of cellulose from glucose is a polycondensation process because a molecule of water is formed during the formation of each C-O-C bond between the glucose units (Figure 4-138). The C-O-C bonds between two saccharides are called glycosidic bonds.
Figure 4-137. Structure of cellulose.
Figure 4-138. Formation of the C-O-C glycosidic bond linking together two β-glucose units.

While cellulose is made up of β-glucose units, starch is a polymer of α-glucose. Furthermore, starch is a mixture of two α-glucose polymers, amylose (10-30%) and amylopectin (70-90%). While amylose is a linear polymer (Figure 4-139), amylopectin is branched (Figure 4-140). The branching in amylopectin occurs at the CH2OH group of some of the glucose units.
Figure 4-139. Structure of amylose.
gure 4-140. Structure of amylopectin.

Watch this video showing how starch and cellulose are made in plants. Unfortunately, while being beautifully crafted and highly illustrative and informative, this video contains some mistakes. Can you find them? [Answer: The glycosidic C-O-C bond in starch is between the carbon atoms in the 1st and 4th positions, whereas in the video this bond is drawn between those in the 1st and 3rd positions. Likewise, the structure of maltose, the α-glucose dimer, is incorrect. Look up the chemical structure of maltose on the Internet.]

The polymer chains of starch and cellulose are long. While the molecular weight of the linear form (amylose) is on the order of hundreds of thousands of a.m.u., the branched form (amylopectin) has a molecular mass of millions of a.m.u. The molecular weight of cellulose varies in a broad range depending on the source, roughly 50,000-300,000 for wood pulp and from ca. 130,000 to over 1,500,000 for cotton and some other plant fibers.

Both starch and cellulose are hydrolyzed on a large industrial scale in a variety of chemical and biochemical processes. In all of these processes, which are the reverse of glucose polycondensation, the C-O-C glycosidic bond is attacked by molecules of water to produce two C-OH moieties. For different applications, the long chains of starch and cellulose can be broken down to glucose, its dimer maltose, shorter glucose polymeric chains (dextrines), or mixtures thereof. For example, in the beer brewing, the starch of malt from barley is hydrolyzed to maltose, which is then fermented by yeast. For making ethanol and biofuel, cellulose is hydrolyzed to glucose.

Let us now consider some interesting reactions of cellulose and starch. Starch forms a remarkably deep-blue complex with the triiodide-anion, I3-, which is produced on addition of an iodide salt such as KI to iodine, e.g.,: KI + I2 = KI3. Amylose of starch wraps around the I3-, to form an inclusion compound, whose structure can be seen here. Watch the appearance of the dark-blue, almost black color on addition of a triiodide salt to a weak colloidal solution of starch in this video. Note that contrary to the widely accepted incorrect view, neither pure iodine (I2), nor iodide (I-) forms the colored compound with starch. Only triiodide does.

The extremely deep color of the starch-triiodide compound makes starch a uniquely sensitive indicator for triiodide and vice versa. Consequently, starch has long been used as the indicator in iodometry, an important method of analytical chemistry. A more recent application of the deeply colored starch-triiodide compound is in counterfeit banknote detection pens (Figure 4-141). These pens are like highlighters, except they are charged with a solution of triiodide rather than with a dye. Modern US and Canadian dollar, euro, UK pound sterling, Swiss franc, and many other Western banknotes are printed on special paper based on pure cellulose (cotton), which, unlike starch, does not produce any deep-colored compounds with triiodide. A counterfeit bill detection pen leaves only a colorless or light-yellow mark on a genuine banknote, but a dark one on a fake banknote printed on regular paper (Figure 4-141). Regular papers are also based on cellulose yet they contain small quantities of starch. Note that these tiny amounts of starch are not present in the pulp used to make regular papers but rather are formed in the paper manufacturing process upon exposure of the pulp to hot steam.
Figure 4-141. Marks left by a counterfeit banknote detection pen on a fake banknote and a genuine banknote (source).

Besides hydrolysis, cellulose undergoes two more industrially significant chemical transformations. One is esterification of the OH groups of cellulose with acetic acid or acetic anhydride, CH3C(O)-O-(O)CCH3. The esterification of only two of the three OH groups on each glucose module gives rise to cellulose acetate (Figure 4-142). When all three OH groups on each link of cellulose have been esterified, cellulose triacetate is produced. Both cellulose acetate and triacetate are used in the production of fibers, textile, films, lacquers, magnetic tape, and membranes. A most recent use of cellulose triacetate is in the production of polarized films for liquid crystal displays.
Figure 4-142. The formation of cellulose acetate (cellulose diacetate) from cellulose.

Another important reaction of cellulose is its nitration to produce guncotton, also known as "smokeless powder" in the U.S.A. and "propellant" in Europe. On treatment of cellulose with nitric acid in the presence of sulfuric acid, all three O-H groups on each glucose link of cellulose are displaced with O-NO2 groups to give nitrocellulose (Figure 4-143). Actually, the name nitrocellulose is not entirely correct as nitro compounds are those containing a C-NO2 bond. A more correct name for nitrocellulose would be cellulose nitro ester.
Figure 4-143. Nitration of cellulose.

Nitrocellulose, which has long replaced classical gun powder, is called "smokeless powder" for a reason. Nitrocellulose does burn without smoke. Moreover, properly prepared nitrocellulose burns so fast that it is safe to set it on fire on the palm of your hand without taking any risk of burning your skin! Hard to believe? Watch this video and this demonstration to see for yourself. In contrast with cellulose itself, and like cellulose acetate and triacetate, nitrocellulose is soluble in some organic solvents, such as diethyl ether and acetone. Solutions of nitrocellulose are used to make wood varnish, fingernail polish, and salicylic acid-based wart removers. Guitar picks and ping-pong balls are made of celluloid, a nitrocellulose-camphor composite.

4.8.3. Exercises.

1. Draw structures of the linear forms of glucose and fructose, gluconic acid, and sorbitol. [Answer: See Figures 4-129, 4-130, 4-131]

2. Draw cyclic structures of α-glucose, β-glucose, fructose, and sucrose. [Answer: See Figures 4-132, 4-135, 4-136]

3. Unlike glucose, fructose has a ketone rather than an aldehyde functional group. In contrast with aldehydes, ketones do not react with Tollens' reagent to give silver metal, nor with Cu(OH)2 to give Cu2O. Fructose, however, reacts with both, as though it were an aldehyde. Why? Answer

4. Glucose has a very high solubility in water. In contrast, the OH-free analog of glucose, hexanal, is very poorly soluble in water. Can you rationalize this difference? Answer

5. Glucose is known to exist in solution largely (>99%) in its cyclic forms, which, unlike the linear form, do not contain an aldehyde group. Nevertheless, glucose is completely oxidized to gluconic acid with Cu(OH)2 or Tollens' reagent. Why? Answer

6. Write balanced chemical equations for lactic acid and alcoholic fermentation reactions of glucose. [Answer: See Figure 4-134]

7. What is inverted sugar? Is inverted sugar sweeter than regular table sugar? [Answer: See Figure 4-136 and accompanying text]

8. Sucrose, a disaccharide, is composed of one glucose unit and one fructose unit. Both glucose and fructose can and do exist in their linear (non-cyclic) forms, but sucrose does not. Why? Answer

9. Two samples were withdrawn from a freshly prepared aqueous solution of sucrose. One sample was treated with Tollens' reagent and the other with Cu(OH)2. No signs of any reaction were observed. The remaining sucrose solution was then treated with a drop of HCl and brought to boiling. After cooling to room temperature, the resultant solution produced silver mirror upon treatment with Tollens' reagent and reacted with Cu(OH)2 to give orange Cu2O. Explain the change in reactivity and write chemical equations for the reactions involved. Answer

10. How is cellulose different from starch? [Answer: See 4.8.2]

11. What is the glycosidic bond? [Answer: See 4.8.2]

12. Cellulose (a) is produced by plants as a source of energy; (b) is composed of β-glucose units; (c) is a polymer of α-glucose; (d) can be used to make ethanol; (e) is a mixture of branched and straight chain polymers of glucose. Answer

13. Write a scheme showing how starch is formed from glucose. [Answer: See 4.8.2]

14. What are amylose and amylopectin? Which of the two has a higher molecular weight? [Answer: See 4.8.2]

15. Naturally occurring cotton (a) is about 98% amylose and 2% amylopectin; (b) is pure amylose; (c) is almost pure cellulose; (d) contains approximately 50% cellulose. Answer

16. When cashing a check at a bank, you were given a 100 dollar bill among other banknotes. The $100 bill looked brand new, never circulated. You put the bill in your shirt pocket and later forgot to take it out before laundering the shirt with other cloths in hot water in a washing machine. The bill survived the washing. But, when you tried to pay with that bill in a store, the salesperson refused to accept it after testing it with a counterfeit banknote detection pen. She showed you the dark mark the pen left on the bill, saying that your banknote was a fake one. Should you blame the bank for giving you a counterfeit bill? Answer

17. Draw a chemical scheme for the reaction of cellulose with nitric acid. Why is the widely used name "nitrocellulose" not entirely correct? [Answer: See Figure 4-143 and accompanying text]