Glucose is the most common monosaccharide. It is known as Dextrose because it occurs in nature principally as the optically active dextrorotatory isomer. Glucose is found in most sweet fruits, especially grapes (20-30%), and honey. It is an essential constituent of human blood. The blood normally contains 65 to 110 mg (0.06 to 0.1%) of glucose per 100 ml. in diabetic persons, the level may be much higher. In the combined form glucose occurs in abundance in cane sugar and polysaccharides such as starch and cellulose.
Preparation of glucose.
Glucose is produced commercially by the hydrolysis of starch with dilute hydrochloric acid at high temperature under pressure.
An aqueous suspension of starch obtained from corn is acidified with hydrochloric acid, It is then heated with high-pressure steam in an autoclave. When the hydrolysis is complete, the liquid is neutralized with sodium carbonate to a pH of 4-5. The resulting solution is concentrated under reduced pressure to get the crystals of glucose.
Uses of glucose.
- As a sweetening agent in syrups and confectionery.
- As food for infants.
- As a reducing agent in the silvering of mirrors and to convert indigo blue to indigo white in vat dyeing.
- As a raw material for wine and alcohol manufacture.
Structure of glucose.
The structure of glucose may be discussed under the following heads.
- Open Chain formula.
- Cyclic structure.
- Haworth representation.
The open-chain formula of glucose is constructed from the following facts:
Elemental analysis and molecular weight determination have established that glucose has the molecular formula C6H12O6.
(2) Presence of 6-carbon unbranched chain.
The complete reduction of glucose with concentrated hydrogen iodide and red phosphorus gives n-hexane. This proves that a glucose molecule is made of an unbranched six-carbon chain.
(3) Presence of 5 OH group.
Glucose reacts with acetic anhydride to form the pentadactyl derivative. This shows the presence of five hydroxy groups. Since glucose is a stable compound, no two OH groups are attached to the same carbon. In other words, the five OH groups are on different carbons.
(4) Presence of the C=O group.
Glucose reacts with hydroxylamine to form an oxime. It suggests the presence of a carbonyl group.
(5) Presence of terminal CHO function.
On mild oxidation with bromine water, glucose is converted to glucose acid which when reduced with an excess of Hl yields n-hexanoic acid.
This shows that glucose contains a six-carbon straight chain with CHO at one end, which has been oxidized to COOH.
(6) Construction of open-chain formula.
Knowing that glucose has a straight 6-carbon chain with a terminal CHO, the five OH groups can be placed one each on the remaining five carbons. Supplying hydrogen atoms to these carbons to satisfy their tetracovalency, the open-chain structure of glucose can be written as :
Configuration of D-Glucose.
The configuration of D-glucose was proved by Emil Fischer by arguments similar to the ones stated below.
(1) Construction of four possible D-pentoses.
Taking the configuration of D-glyceraldehyde as the standard, two possible D-aldotetroses (A and B) may be constructed by adding a CHOH just below CHO, placing OH to the right and then to the left.
Similarly, each of the two D-tetroses (A and B) gives two D-aldopentoses. Thus four possible D-aldopentoses are :
(2) D-Arabinose has configuration II or IV.
Oxidation of D-arabinose with nitric acid oxidizes the terminal CHO and CH2OH groups yielding two optically active (asymmetric) dicarboxylic acids. The forms II and IV can form two optically active (asymmetric) diacids, while I and III can give meso acids only that has a plane of symmetry. Therefore, D-arabinose is either II or IV.
(3) Configuration II confirmed for D-arabinose.
D-arabinose by Killiani -Fischer synthesis yields two epimeric aldohexoses, D-glucose and D-mannose. These on oxidation with nitric acid form two optically active (asymmetric) dicarboxylic acids. This is theoretically possible only if D-arabinose has the configuration II and not IV.
Proceeding similarly, you will find that if D arabinose had configuration IV, of the two dicarboxylic acids derived from it, one would be meso and one asymmetric (optically active). Hence D-arabinose has configuration II.
(4) Ruff degradation of D-glucose and D-mannose produces D- arabinose in each case.
In ruff degradation, the CHOH below CHOH is destroyed. Therefore, the configuration of the two aldohexoses, D-glucose and D-mannose, can be derived by adding a new CHOH below CHO in form II of D-arabinose.
Hence D-glucose has configuration V or VI.
(5) D-glucose and L-glucose yield the same dicarboxylic acid.
This means that these two sugars differ only in respect of the position of the terminal groups (CHO and CH2OH). Therefore, the exchange of the terminal groups in D-glucose should be able to give a different aldohexose (L-glucose). Let us now examine configuration formulas V and VI (One of which is D-glucose) from this angle.
If VII is rotated through 180° in the plane of the paper, it gives an aldohexose VIII, different from V. A similar procedure with formula VI does not give rise to a different sugar.
From the above arguments, it is evident that D-glucose has the configuration as shown by the from V.
Cyclic Structure of D-Glucose.
(1) Open-Chain Structure not wholly true.
Fischer realized that the open-chain pentahydroxy aldehyde structure of glucose did not wholly explain its chemical behavior. Unlike simple aldehydes, glucose did not form the crystalline bisulfite compound and failed to give the shiff’s test. Furthermore, the penta-acetate and pentamethyl-ether derivatives of glucose are not oxidized by Tollens’ regent or Fehling’s solution, indicating the absence of CHO group.
(2) The cyclic structure suggested explaining mutarotation.
The French chemist Tarnet established the existence of two crystalline forms of glucose, α-glucose, and β-glucose. α-Glucose had specific rotation +112°, while β-glucose + 19°. The optical rotation of each of these forms changed gradually with time till finally a constant value of +53° was reached. To explain this phenomenon of mutarotation, it was visualized that the α and β glucose were, in reality, the cyclic hemiacetal forms of glucose which were interconvertible via the open-chain form. The constant value of + 19° represented the state of equilibrium between α-D-glucose and β-D-glucose.
The concentrations of α-D glucose, β-D-glucose, and the open-chain glucose at equilibrium are 36%, 64%, and less than 0.01% respectively. This explains why D-glucose can react both as an aldehyde and a cyclic hemiacetal in which CHO is absent.
(3) Glycoside formation confirms the cyclic structure.
Glucose when treated with methanol in the presence of dry HCl, gives two isomeric acetals or glycosides,. These crystalline glycosides, methyl-α-D-glucose, and methyl-β-D glucoside have been actually isolated. These are optically active but do not give any reactions to the free CHO group. Evidently, the two glycosides are the methyl derivatives of α– and β-D-glucose, formed as a result of the reaction between the hemiacetal OH of these forms and methanol.
thus the cyclic structure of D-glucose stands confirmed but whether it has a 5-membered or a 6-membered ring is still to be proved.
(4) Determination of ring size.
So far we have represented the structure of cyclic hemiacetals or anomers of D-glucose as having a ring of six members, five carbons and one oxygen. This has been proved to be correct and a five-membered ring has been ruled out.
Hirst (1926) prepared tetra-O-methyl-D-glucose. by treating methyl-D-glucoside with dimethyl sulfate and subsequent acid hydrolysis of the pentamethyl derivative formed. The oxidation of tetra-O-methyl-D-glucose with nitric acid yielded trimethoxyglutaric acid.
Obviously, the two carboxylic carbons (1,5) of the trimethoxyglutaric acid are the ones originally involved in a ring formation. Hence, there must have existed an oxide ring between C-1 and C-5. Tracing back the reaction sequence, it stands proved that D-glucose has a six-membered ring. The presence of a 6-membered ring in D-glucose has also been confirmed by x-ray analysis.
The Haworth Representation.
So far we have used Fischer projection formulas for representing the cyclic forms of D-glucose. Haworth thought that these structures were awkward. He introduced the hexagonal representations resembling the heterocycle pyran which contains five-carbon and one oxygen in the ring. Thus, he claimed the names α-D-glucopyranose and β-D-glucopyranose for the hexagonal structures of α-D-glucose and β-D-glucose.
It may be noted that in Haworth formula, all the OH groups on the right in Fischer formula are directed below the plane of the ring, while those on the left go above the plane. The terminal CH2OH projects above the plane of the ring.
Physical properties of glucose.
Glucose is a white crystalline solid, mp 146°C. When crystallized from cold water, it forms glucose monohydrate (C6H12O6.H2O), mp 86°C. it is extremely soluble in water, only sparingly so in ethanol, and insoluble in ether. It is about three-fourths as sweet as cane sugar (sucrose). It is optically active, and the ordinary naturally occurring form is (+)-glucose.
Chemical properties of glucose.
We have seen that D-glucose is an equilibrium mixture of a straight-chain form and a cyclic hemiacetal form.