Heterocyclic Chemistry
N
Chapter 5 Carbohydrates
Part II
S
O
Heterocyclic Chemistry
Physical properties of monosaccharides
 Carbohydrates are polar due to they contain a large number of hydroxyl
groups
Thus they are soluble in water and other polar solvents but insoluble in non
polar solvents.
They have very high boiling points due to their molecules can form Hbonds; e.g. glyceraldehyde boils at 150 °C
Chemical Reactions of monosaccharides
 Many of the reactions of monosaccharides are those expected of their
functional groups (carbonyl and hydroxyl).
 These reactions occur to them in open chain forms.
 It is preferred to avoid using bases in their reactions due to in basic medium
side reactions take place which involve removal of the acidic proton (next to
carbonyl group) to give enolate anion that may reacquire a proton to give the
original sugar or its epimer (e.g. conversion of glucose to mannose).
Also the enolate anion may convert to enediol that then converts to a
different enolate and eventually isomerizes to a functional sugar (e.g. CHO
group convert to C=O group as in interconversion of glucose to fructose).
Heterocyclic Chemistry
Interconversion of glucose , mannose and fructose
O
H
B
H
C
H
OH
HO
H
HO
HO
H
H
OH
H
OH
H
OH
H
OH
H
OH
H
OH
H
H
OH
H
OH
CH2OH
D-fructose
H
H-OH
OH
O
HO
H-OH
H-OH
H
Enolate
C
Epimerization
Isomerization
OH
H
H
H
OH
H
OH
CH2OH
Enolate
C
HO
H
OH
OH
O
HO
CH2OH
CH2OH
D-Glucose
CH
C
O
OH
OH
CH2OH
H
C
H
O
OH
H
O
C
HO
H
HO
H
H
OH
H
OH
H
OH
H
OH
CH2OH
Enediol
Heterocyclic Chemistry
CH2OH
D-Mannose
I- Reduction of monosaccharides
 Since they contain carbonyl group in the form of aldehydic or ketonic group
these groups can be reduced by reducing agents such as NaBH4 or catalytic
hydrogenation (H2 / Ni) to the corresponding alcoholic group i.e. to a primary or
secondary alcoholic group respectively.
 The name of the resulting polyhydroxy compound is derived by replacing the
suffix ose in the sugar name by itol
e.g1. Reduction of glucose to glucitol (sorbitol) where the aldehydic group is
reduced to a primary alcoholic group that is not a stereogenic center
CHO
OH
OH
H
H O
HO
H
H
H
OH
OH
OH
H
 -D-glucose
CH2OH
OH
H
H
H2 / Ni
OH
HO
H
H
OH
H
OH
H
OH
H
OH
CH2OH
D-glucose
CH2OH
D-glucitol
D-Sorbitol
sweetner -sugar
substitute
Heterocyclic Chemistry
I- Reduction of monosaccharides
e.g2. Reduction of fructose to glucitol and mannitol
 Reduction of fructose results in the formation of two alditols due to the
carbonyl group exists in the form of a ketonic group that upon reduction gives
a secondary alcoholic group which is considered as a new stereogenic center
that can exist as a pair of enantiomers at that center only
CH2OH
CH2OH
HO
O
O
H
HO
OH
H
OH
HO
H
 -D-fructofuranose
CH2OH
H
H
NaBH4
HO
OH
H
H
OH
H
OH
H
OH
H
OH
CH2OH
D-fructose
Heterocyclic Chemistry
CH2OH
CH2OH
HO
H
+ HO
H
H
OH
H
OH
CH2OH
D-glucitol
D-mannitol
(epimers at C2)
II- Oxidation of monosaccharides
 Aldoses can be oxidized easily but the product of oxidation depends on the
oxidizing agent used.
 Although ordinary ketones resist oxidation, ketoses can be oxidised
specially in the basic medium due to they will isomerize to aldoses thus
being oxidized easily.
a) Oxidation by bromine water (Br2 / H2O)
 This reagent oxidize selectively CHO group to COOH group and since this
reagent is acidic no epimerization or isomerization can take place thus this
reagent can be used to differentiate between aldoses and ketoses.
O
H
O
OH
C
C
(CHOH)n
Br2 / H2O
(CHOH)n
CH2OH
CH2OH
Aldose
if n=4 , glucose
Aldonic acid
gluconic acid
Heterocyclic Chemistry
II- Oxidation of monosaccharides
b) Oxidation by nitric acid (HNO3)

This reagent oxidize both aldehydic and primary alcoholic group to give
dicarboxylic acid known as aldaric acid
H
O
O
C
(CHOH)n
HNO3
OH
C
(CHOH)n
CH2OH
COOH
Aldose
if n=4 , glucose
Aldaric acid
glycaricacid
Saccharic acid
c) Oxidation by Tollen’s reagent
 Tollen’s reagent can be used to differentiate between simple aldehydes and
ketones where simple aldehydes give +ve result (sliver mirror due to reduction
of Ag+1 ions in the reagent by the aldehyde to Ag0) while ketones give –ve
result.
 However this reagent can not be used to differentiate between aldoses and
ketoses since both of them give +ve result this due to ketoses isomerize to
aldoses by this reagent which is basic in nature.
Sugars which give +ve results with Tollen’s called reducing sugars.
Heterocyclic Chemistry
II- Oxidation of monosaccharides
CHO
H
H OH
HO
HO

H
H
OH
HO
H O
H
OH
OH
COOH
H
H
HO
Ag(NH 3)2OH
H
OH
H
OH
oxidizing agent
H
H
OH
H
OH
CH 2OH
+ Ag0
silver mirror
CH 2OH
Glucose
open chain f orm
Reducing sugar
Glucopyranose
(hemiacetal form)
OH
Gluconic acid
 Monosacharides give + ve result with Tollen’s reagent if they exist in open
chain form or hemiacetal or hemiketal cyclic forms (pyranose or furanose
forms).
However, if the monosaccharides exist in the form of glucosides (acetals or
ketal forms) in this case they give –ve results with Tollen’s and described as
non reducing sugars.
H OH
HO
HO
HO
H
H
acetal
HO
O
H
H
OH 
OCH3
CH2OH
OH 
H
methyl-  -D-glucoside
acetal
OCH2CH3
H
HO
ethyl- - D-fructoside
Ag(NH3)2OH
No reaction
Heterocyclic Chemistry
III- Glycosides formation (sugar acetals and ketals)
 Cyclic hemiacetal and cyclic hemiketal forms of monosaccharides convert to
acetals and ketals (diethers) respectively upon reaction with alcohols in the
presence of catalytic amounts of dry acids.
 The new C-O bond is called glycosidic linkage
 The alkoxy group at the anomeric carbon is known as aglycon and the formed
acetal as glycoside
H OH
H OH
H O
HO
HO
H
H
H
OH
OH
 -Glucopyranose
Hemiacetal
H O
CH3OH / H+ HO
HO
H2O / H+
H
H
H
-glycosidic linkage
OH
O
CH3
methyl- -D-glucoside
Acetal
 These glycosides are non reducing sugars due to absence of free OH group
at the anomeric carbon thus they can not reopen to give the open chain form
which then undergoes oxidation.
Heterocyclic Chemistry
IV- Ether formation
H OH
H OCH3
H O
HO
HO
CH3I, Ag2O
H
H
OH
H
H O
H 3 CO
H 3CO
OH
H
OCH 3
OCH3
H
H
Methyl-2,3,4,6-tetra-O-methyl- -D-glucopyranoside
 -Glucopyranose
Hemiacetal
V-Ester formation
OH
HO
O
H
OH
H
O
(CH3CO)2O / pyridine
CH2OH
HO
O-COCH3
H3COCO
H
H
OCOCH3
H
H3COCO
CH2OCOCH3
H
 -D-fructofuranose
Heterocyclic Chemistry
VI-Osazone formation (reaction with phenyl
hydrazine)
 When aldoses and ketoses are treated with an excess of phenyl hydrazine,
they are converted into well defined crystalline structures known as
osazones that have different shapes thus they are used for identification
purposes.
 An osazone is a phenyl hydrazone derivative of both C1 and C2 of an
aldose or a ketose thus the configuration at these carbons is destroyed
resulting in that a sugar and its epimer at C2 give the same osazone ( e.g.
mannose and glucose) also a sugar and its functional isomer give the
same osazone (e.g. glucose and fructose).
O
H
CH2OH
C
CHOH
or
H
C=O
excess Ph- NH-NH2
(CHOH)n
(CHOH)n
CH2OH
CH2OH
Aldose
Ketose
H+
C=N-NHPh
C=N-NHPh
(CHOH)n
CH2OH
Osazone
Heterocyclic Chemistry
VI-Osazone formation (reaction with phenyl
hydrazine)
CHO
CHO
CHO
H
OH
HO
H
H
OH
H
OH
H
OH
H
OH
H
OH
H
OH
CH2OH
CH2OH
D-Allose
D-Atrose
CHO
H
OH
HO
H
OH
H
OH
H
OH
H
OH
CH2OH
CH2OH
D-Arabinose
D-Ribose
These two sugars give the same osazone
H
These two sugars give the same osazone
VII-Ruff degradation (it leads to reduction of
length of the aldose chain)
CHO
HO
COOH
H
H
OH
H
OH
CH2OH
D-Arabinose
(5 C)
HO
Br2 / H2O
H
H
CHO
H
OH
OH
CH2OH
H2O2
Fe2(SO4)3
H
OH
H
OH
+ CO2
CH2OH
(4C)
 Since this reaction involves C1 & C2 in the aldose chain, thus sugars
have the same configuration at the other carbons give the same product
Heterocyclic Chemistry
VIII- Kiliani- Fischer synthesis
 This reaction is used to increase the length of the aldose chain where a
new carbon is added and the original aldehydic group convert to a
secondary alcoholic group and becomes atom number 2.
O
H
CN
C
CHOH
CHOH
(CHOH)n
CH2OH
Aldose
HCN
CHOH
(CHOH)n
CH2OH
H3O+
COOH
CHO
CHOH
CHOH
CHOH
Na(Hg)
CHOH
(CHOH)n
(CHOH)n
CH2OH
CH2OH
Heterocyclic Chemistry
Di-, Oligo- and Poly-saccharides
These sugars are formed via biochemical condensation of two ( or more)
monosaccharides by the elimination of water molecule from two OH groups
present on the two sugars.
Most commonly the reaction occurs between the OH present on C1
(anomeric carbon) of one monosacharide and that on C4 of the second to form
a1
4 glycosidic linkage. Because the reaction involves C1, which can
exist in either α- or β- forms, we can obtain either α (1
4) or β (1
4)
glycosidic linkage.
Glycosidic linkages to other carbon atoms are fairly common, notably 1
2
And 1
6.
Some disaccharides are reducing sugars and others are non reducing
depending on whether or not there is a hemiacetal or hemiketal at any on of
the anomeric carbons.
α (1
4) Glycosidic linkage.
β (1
4) Glycosidic linkage.
Heterocyclic Chemistry
Important disaccharides
glucose unit
1
glucose unit Free OH
galactose unit
1
4
Maltose
α-D(glucopyranosyl)-(1
β-D glucopyranose
Reducing sugar
Sucrose (Table sugar)
α-D(glucopyranosyl)-((1
Non reducing sugar
4)-
glucose unit
Free OH
4
Lactose (Cow’s & human milk)
β-D(galactopyranosyl)-(1
4)-β-D glucopyranose
Reducing sugar
2)-β-fructofuranoside
Heterocyclic Chemistry
Polysaccharides
 Polysaccharides contain hundreds or thousands of carbohydrate units
 All of them are non reducing sugars, since the anomeric carbons are
connected through glycosidic linkages
 Examples: starch, glycogen and cellulose ; all of them are polymers of
glucose
 There are two forms of starch; amylose and amylopectin
Starch -Amylose (10-20 %)
Starch- Amylopectin(80- 90 %)
Heterocyclic Chemistry
Polysaccharides
 Glycogen (animal starch), structurally similar to amylopectin, containing
both α(1
4) glycosidic linkages and α(1
6) branch points but it is more
branched
 It is abundant in the liver and muscles.
 Cellulose (in plants and wood), it is unbranched polymer made of β-Dglucose units i.e contains β(1
4) glycosidic linkages
Heterocyclic Chemistry