Organic Chemistry: Concepts and Applications - Headley Allan D. 2020
Synthetic Polymers and Biopolymers
20.15 Reactions of Monosaccharides
20.15.1 Hemiacetal Formation Involving Monosaccharides
The reactions that monosaccharides undergo are the same as those of molecules that have the same functionalities, alcohols and aldehyde and were covered in earlier chapters. Hemiacetal formation reactions involve an addition reaction of alcohols to an aldehyde to form hemiacetals, as shown in Reaction (20-53).
(20-53)
Monosaccharides contain both functionalities on the same molecule, and as a result, the possibility exists for intramolecular reactions. Cyclic hemiacetal formation reactions are one of the most important reactions of monosaccharides. An example of an intramolecular hemiacetal formation reaction is given in Reaction (20-54).
(20-54)
Problem 20.15
Give the cyclic hemiacetal or hemiketal for each of the compounds shown below.
A similar intramolecular reaction occurs with glucose as shown in Reaction (20-55).
(20-55)
Note that the two hemiacetal products are stereoisomers and are known as anomers. These two stereoisomers differ from each other in the orientation of the OH; the OH group can be in the equatorial position (up) or in the axial position (down) of this six-member cyclic compound. Anomers are diastereomers that differ in configuration around only one atom, the anomeric atom. The reaction given in Reaction (20-55) can be represented differently in an aqueous solution and is shown in Reaction (20-56) to better illustrate the equatorial and axial groups.
(20-56)
The name of these cyclic hemiacetals is derived from pyran due to the similarity of the structure of both these compounds; both structures are six-member ring compounds, which contain an oxygen atom as part of the ring.
The cyclic hemiacetal of glucose is called a glucopyranose. The carbon at which the reaction takes place is called the anomeric carbon as shown in Reaction (20-55). Both anomers have a root name of D-glucose since the starting compound is D-glucose. The Greek letters α and β are used to differentiate these anomers; if the OH group is down or axial, the α notation is used, and if the OH group is up or equatorial, the β notation is used. Since the hemiacetal reactions are equilibrium reactions, all three species exist in equilibrium in solution; however, one dominates in concentration at equilibrium. The chair conformer of glucopyranose that has the OH group in the equatorial position is the more stable conformation and hence the one that is in abundance, compared to the other isomers, as shown in Reaction (20-57). The equatorial position has more room to accommodate the fairly large OH group, and hence this epimer is more stable, compared to the other epimer, which has the OH in the axial position.
(20-57)αβ
Problem 20.16
Give the most stable product for the hemiacetal formation of galactose.
You may be wondering if there are other possible cyclic hemiacetals that could be formed? The answer is yes; however, the formation of seven-member ring hemiacetal is more difficult, compared to six-member ring hemiacetals. The five-member ring hemiacetal is however fairly stable and easier to form than the seven-member ring due to the proximity of the two reacting groups. The reaction for the formation of the five-member ring hemiacetal is shown in Reaction (20-58).
(20-58)αβ
The root name of these five-member ring hemiacetals is derived from furan, which is a five-member cyclic compound which contains four carbons and one oxygen.
A similar system as that described for the nomenclature of different six-member ring hemiacitals (anomers) of glucose can be used to name the different epimers of the five-member ring hemiacetals of glucose. There are two possible anomers; in this case, however, the anomers are called glucofuranose and specifically α-D-glucofuranose and β-D-glucofuranose, depending on the orientation of the —OH group as shown in Reaction (20-58).
20.15.2 Base-catalyzed Epimerization of Monosaccharides
Since the α-hydrogen of monosaccharides is acidic, in the presence of a base, that proton can be abstracted to form an enolate anion, as shown below in Reaction (20-59).
(20-59)
Since the enolate anion formed is sp2 and flat, it can acquire another proton for the solvent, this proton can add to either side to create the opposite configuration of the original conformer as shown in Reaction (20-60).
(20-60)
As shown in the reaction, there is a mixture of glucose and mannose.
20.15.3 Enediol Rearrangement of Monosaccharides
Another reaction that is possible once the enoate is formed by the removal of the α-hydrogen of glucose is a possible rearrangement to form the keto monosaccharide as shown in Reaction (20-61).
(20-61)
20.15.4 Oxidation of Monosaccharides with Silver Ions
Since monosaccharides have an aldehyde functionality, and as we saw in Chapter 11, aldehydes are easily oxidized to carboxylic acids or carboxylate salts, depending on the reagent used. If the monosaccharide is shown in the hemiacetal form, it is not immediately obvious that it can be oxidized, but in solution, there is an equilibrium between the open chain aldehyde and the hemiacetal forms, and it is the aldehyde form that is oxidized. The Tollen's reagent is often used as a mild oxidizing reagent to test the presence of a monosaccharide of an unknown sample. The presence of a silver mirror is an indication of the presence of the aldehyde functionality as shown in Reaction (20-62).
(20-62)β
Other reagents that are frequently used for the oxidation of monosaccharides include the Benedict's Reagent and the Fehlings Reagent. Both reagents contain Cu2+, which is blue colored, and its reaction with a monosaccharide gives Cu2O, which is a red solution. The main difference between the two reagents is that the Benedict's solution has a citric acid complex, whereas the Fehling's reagent is made with a tartaric acid complex, but a color change is an indication of the presence of a monosaccharide that was oxidized.
20.15.5 Oxidation of Monosaccharides with Nitric Acid
Another important oxidation reaction is shown below, in which the terminal hydroxyl group of glucose is oxidized to a carboxylic acid using nitric acid to form glucaric acid as shown in Reaction (20-63).
(20-63)
D-Glucaric acid, also known as saccharic acid, is a good chelating agent; its salt is used in dishwasher detergents to assist in the chelation of calcium and magnesium ions, which makes detergents more efficient in hard water. As you can imagine, the primary alcohol is much easier to oxidize, compared to the other alcohols, which are secondary.
20.15.6 Oxidation of Monosaccharides with Periodic Acid
As we have seen from Chapter 11 on oxidation reactions, periodic acid is used to oxidize and cleave the carbon—carbon single bonds of compounds that have 1,2-diols functionalities. Examples are given in Reactions (20-64) and (20-65).
(20-64)
(20-65)
Note the products that are produced from each carbon that contained the hydroxyl functional group. This type of oxidation occurs with not only alcohols that are adjacent to each other but also molecules that contain the two oxidizable functionalities in a 1,2-relationship as shown in Reaction (20-66).
(20-66)
Problem 20.17
1. Give the products for the periodic oxidation reaction shown below and predict how many moles of products are formed.
2. Give the structure of an unknown monosaccharide, if after oxidation, 4 mol of formic acid and 2 mol of formaldehyde are produced.
20.15.7 Reduction of Monosaccharides
The reduction of glucose gives a very important compound that is used as a sugar substitute and the reaction is given in Reaction (20-67).
(20-67)
20.15.8 Ester Formation of Monosaccharides
Each monosaccharide has several alcohol functionalities, and as we saw in Chapter 7, alcohols react with carboxylic acid derivatives, such as acid chlorides or acid anhydrides, to form esters as shown in Reaction (20-68), Ac = CH3CO2 (acetate).
(20-68)β
20.15.9 Ether Formation of Monosaccharides
The alcohol groups of monosaccharides can be alkylated with alkyl halides using a substitution reaction that was used for the synthesis of ethers. This type of reaction you will recall involves the use of a base to deprotonate the hydrogen of the alcohol functionality, followed by a substitution reaction using an electrophilic alkyl halide. This reaction involving glucopyranose is shown in Reaction (20-69).
(20-69)β
20.15.10 Intermolecular Acetal Formation Involving Monosaccharides
As we have seen in Chapter 12, the reaction of an aldehyde with 2 mol of an alcohol gives an acetal after first forming a hemiacetal as shown in Reaction (20-70).
(20-70)
The same type of reaction can occur with difunctional molecules. First, an intramolecular reaction would yield the cyclic hemiacetal, followed by the reaction with a mole of an alcohol that would yield an acetal, as shown in the example given in Reaction (20-71).
(20-71)
Problem 20.18
Give the acetal that will result from the reaction of methanol with each of the following compounds.
A similar reaction occurs with monosaccharides, a glycopyranoside results as shown in Reaction (20-72).
(20-72)ββ
Based on the mechanism for the acetal formation, an equal mixture of epimer will be the product as shown below in Reaction (20-73).
(20-73)ββα
We will see in the next section that glycoside bonds are the bonds of polysaccharides that are formed from the monosaccharides.