A novel mechanism for the oxidation of erythro-series pentoses and hexoses by N-arylbromosulphonamides in alkaline medium

Article abstract of DOI:10.1081/CAR-120004334

Kinetic studies of the oxidation of D-mannose, D-glucose, D-fructose, L-arabinose and D-ribose by bromamine-T (sodium N-bromo-p-toluenesulphonamide or BAT) and bromamine-B (sodium N-bromobenzenesulphonamide or BAB) in alkaline medium were investigated at 30°C. The rate of the reaction was first order both with respect to the oxidant and the sugar and second order with respect to [HO^-]. The addition of the reaction product, p-toluenesulphonamide (PTS) or benzenesulphonamide (BSA), and the variation of ionic strength of the medium have no effect on the rate. The rate decreases with decrease in dielectric constant of the medium and values of d_AB, the size of activated complex, were calculated. Proton inventory studies were made in H₂O-D₂O mixtures. The activation parameters of the reaction were computed from Arrhenius plots. HPLC and GLC-MS analysis of the products indicated that the sugars were oxidized to a mixture of aldonic acids consisting of arabinonic, ribonic, erythronic and glyceric acids. A general mechanism consistent with the observed results has been proposed.

Full text of DOI:10.1081/CAR-120004334

Journal of Carbohydrate Chemistry
ISSN: 0732-8303 (Print) 1532-2327 (Online) Journal homepage: http://www.tandfonline.com/loi/lcar20
A NOVEL MECHANISM FOR THE OXIDATION OF
ERYTHRO-SERIES PENTOSES AND HEXOSES BY
N-ARYLBROMOSULPHONAMIDES IN ALKALINE
MEDIUM
V. Shashikala & K. S. Rangappa
To cite this article: V. Shashikala & K. S. Rangappa (2002) A NOVEL MECHANISM
FOR THE OXIDATION OF ERYTHRO-SERIES PENTOSES AND HEXOSES BY N-
ARYLBROMOSULPHONAMIDES IN ALKALINE MEDIUM, Journal of Carbohydrate Chemistry,
21:3, 219-234
To link to this article: http://dx.doi.org/10.1081/CAR-120004334
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J. CARBOHYDRATE CHEMISTRY, 21(3), 219–234 (2002)
A NOVEL MECHANISM FOR THE
OXIDATION OF ERYTHRO-SERIES
PENTOSES AND HEXOSES BY
N-ARYLBROMOSULPHONAMIDES
IN ALKALINE MEDIUM
*
V. Shashikala and K. S. Rangappa
Department of Studies in Chemistry, University of Mysore,
Manasagangotri, Mysore-570006, India
ABSTRACT
Kinetic studies of the oxidation of d-mannose, d-glucose, d-fructose, l-
arabinose and d-ribose by bromamine-T (sodium N-bromo-p-toluenesul-
phonamide or BAT) and bromamine-B (sodium N-bromobenzenesulpho-
namide or BAB) in alkaline medium were investigated at 30°C. The rate
of the reaction was first order both with respect to the oxidant and the
sugar and second order with respect to [HOꢀ ]. The addition of the
reaction product, p-toluenesulphonamide (PTS) or benzenesulphonamide
(BSA), and the variation of ionic strength of the medium have no effect
on the rate. The rate decreases with decrease in dielectric constant of the
medium and values of dAB, the size of activated complex, were cal-
culated. Proton inventory studies were made in H2O–D2O mixtures. The
activation parameters of the reaction were computed from Arrhenius
plots. HPLC and GLC-MS analysis of the products indicated that the
sugars were oxidized to a mixture of aldonic acids consisting of arabi-
*
Corresponding author. Fax: +91-821-518835, +91-821-421263; E-mail: rangappaks@yahoo.com
219
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220
SHASHIKALA AND RANGAPPA
nonic, ribonic, erythronic and glyceric acids. A general mechanism con-
sistent with the observed results has been proposed.
Key Words: Erythrose series sugars; Oxidation; Bromamine-T;
Bromamine-B; Kinetics; Mechanism
INTRODUCTION
Aldo and ketohexoses and pentoses have been oxidized with several oxidants.
Kinetics of oxidation of sugars by halogens[1–3] and copper (II)[4,5] in alkaline medium
are reported, but the information in the literature on the oxidation of sugars by N-
arylhalosulphonamides is very scanty. In this laboratory, we have already studied the
oxidation of hexoses, pentoses, amino sugars and uronic acids by both chloramine-T
(CAT) and chloramine-B (CAB) in alkaline medium.[6–9] However, the bromine
analogues of N-arylhalosulphonamides have not been extensively used for oxidation of
sugars. It was, therefore, of interest to compare the oxidation of hexoses and pentoses
by bromamine-T (BAT) and bromamine-B (BAB) with that of their chlorine analogues.
In this paper, we have reported the kinetics of oxidation of three hexoses, namely,
d-glucose, d-mannose and d-fructose, and two pentoses, namely, l-arabinose and d-
ribose, with BAT and BAB in alkaline medium at 30°C and compared the results with
those of their chlorine anologues (CAT and CAB).[6,7] Each sugar is oxidized to a
mixture of several aldonic acids. Pentoses form mainly pentonic acids as major pro-
ducts, but hexoses also form pentonic acids. In the case of hexoses, oxidation occurs
mainly with the cleavage of the C-1–C-2 and C-2–C-3 bonds, whereas pentoses oxi-
dize mainly with cleavage of C-1–H and C-1–C-2 bonds. On the basis of the above
results, a novel mechanism for the oxidation of erythro-series sugars by N-arylbro-
mosulphonamides is proposed.
RESULTS AND DISCUSSION
The reactions were carried out with varying concentrations of the oxidant (BAT
or BAB) at constant [HOꢀ ] and [S]o with substrate (S) in large excess. Plots of log
[OX] vs time, where OX is oxidant, were linear indicating a first order dependence of
the reaction rate on [BAT]o or [BAB]o. The pseudo first order rate constants kobs
obtained with different [OX]o were similar, confirming the first order dependence of
the rate on [OX]o (Table 1). The kobs values increased with increase in [S]o (Table 1).
The plots of log kobs vs. log [S]o were linear with unit slopes. The second order rate
constants (k2 = kobs/[S]o) were constant within the experimental errors demonstrating a
first order dependence of the rate on [S]o. Furthermore, the plots of kobs vs. [S]o gave
straight lines (Figure 1) passing through the origin indicating that the intermediates
formed are of transient existence. At constant [OX]o, [S]o and temperature, values of
kobs increased with an increase in [NaOH] (Table 2). The plots of log kobs vs. log
[HO ꢀ ] were linear with slopes of 2, indicating a second order dependence of the rate
on [HO ꢀ ]. Addition of the reaction products, p-toluenesulphonamide (PTS) or ben-
zenesulphonamide (BSA) (0.008 M), and Br- and Cl ꢀ ions had negligible influence on

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ERYTHRO-SERIES PENTOSES AND HEXOSES
221

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222
SHASHIKALA AND RANGAPPA
50
45
40
35
30
25
20
15
10
5
A-[D-Man]
B-[D-Glu]
C-[D-Fru]
D-[L-Ara]
E-[D-Rib]
a-[D-Man]
b-[D-Glu]
c-[D-Fru]
d-[L-Ara]
e-[D-Rib]
0
0
10 20 30 40 50 60 70
70 60 50 40 30 20 10
102 [S]0 (M)
0[BAB]
Figure 1. Plots of kobs vs. [S]o; [BAT]o = 2.00 ꢁ 10ꢀ3 M, [HOꢀ ] = 2.00 ꢁ 10ꢀ2 M, temp = 30°C.
A, B, C, D and E refer to BAT and a, b, c, d and e refer to BAB.
the rate of reaction. The rate of oxidation of sugars was unaltered when ionic strength
(I) of the medium was changed using sodium perchlorate. When the solvent com-
position of the medium was varied by adding methanol (0 to 40% v/v), the reaction rate
decreased with increasing methanol content of the medium. Plots of log kobs vs. 1/e (e-
dielectric constant of the medium) were linear with negative slopes (Figure 2). The
reactions were studied at different temperatures (298 to 318 K) and the Arrhenius plots
of log kobs vs 1/T were found to be linear. The activation parameters for the composite
reaction were calculated (Table 3). The solvent isotope studies were made in D2O and
the ratios, kobs(H2O)/kobs(D2O) were 0.5 to 0.56 (Figure 3).
Proton inventory studies were made in H2O–D2O mixtures (Table 4). Addition of
an aqueous solution of acrylamide to the reaction mixture did not cause polymerization,
showing the absence of free radical species during oxidation. A comparison of HPLC
and GLC-MS retention times of the reaction products with those of the standards,
indicated that arabinonic, ribonic, erythronic and glyceric acids are the major oxidation
products for all the erythro-series sugars. In addition to these acids, small proportions
of hexonic acids were formed from hexoses (Figure 4, Table 5). Incubation of sugars
with alkali alone under the reaction conditions did not degrade the sugars.
The oxidation products of sugars were also analyzed at 0.5, 1, 2, 4, 8, 16 and
24 h. The formation of various six-carbon aldonic acids was observed only after 4 h,

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SHASHIKALA AND RANGAPPA
A-[D-Man]
B-[D-Glu]
C-[D-fru]
D-[L-Ara]
E-[D-Rib]
a-[D-Man]
b-[D-Glu]
c-[D-Fru]
d-[L-Ara]
e-[D-Rib]
2.6
2.1
1.6
1.1
0.6
1.2 1.3 1.4 1.5 1.6 1.7 1.8
1.8 1.7 1.6 1.5 1.4 1.3
1.2[BAB]
100/ε
Figure 2. Plots of log kobs vs. 1/D; [BAT]o = [BAB]o = 2.00 ꢁ 10ꢀ3 M, [S]o = 3.00 ꢁ 10ꢀ2
M, [HO ꢀ ] = 2.00 ꢁ 10ꢀ2 temp = 30°C. A, B, C, D and E refer to BAT and a, b, c, d and e refer
to BAB.
revealing that the lower carbon aldonic acids were not derived from the initially formed
six-carbon aldonic acids.
Similar products were observed even when the reactions were carried out under
kinetic conditions mentioned in Tables 1 and 2.
The identical orders observed with respect to both oxidant (BAT or BAB) and all
sugars suggest a common mechanism for the oxidation process. The organic hal-
oamines behave as strong electrolytes in aqueous solutions and the several equilibria
present are predominantly pH dependent.[10,11] Although the oxidizing species in
acidic solutions of BAT or BAB are RNBrH and RNBr2 and hypobromous acid, it
has been established that in alkaline medium RNBrꢀ is the active oxidant[12–14] (R =
p-CH3C6H4SO2 for BAT and R= C6H5SO2 for BAB).
In alkaline solution, sugars undergo enolization to form enediolate anions in the
absence of other reactants. These anions undergo epimerizaton and isomerization
(Lobry de Bruyn–Alberda Van Ekenstein transformation) to form a mixture of isomeric
aldoses and ketoses. However, in the presence of BAT or BAB the enediolate anions
(E ꢀ ) react with RNBr ꢀ to form intermediate (X), which in turn undergoes a cleavage
to form products (Table 5).

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ERYTHRO-SERIES PENTOSES AND HEXOSES
225
Scheme 1. Kinetic scheme.
In view of the observed first order dependence of the rate on oxidant and [S]o and
second order dependence on [HO ꢀ
the following reaction sequence (Scheme 1) is
proposed for the oxidation of sugars by BAT or BAB in alkaline medium.
]
o,
Rate ¼ k3½XŠ½HOꢀŠ
ð1Þ
or
2
K1K2k3½SŠ½OXŠ ½HOꢀŠ
t
Rate ¼
ð2Þ
½H2OŠ½1 þ K2½EꢀŠŠ
where [OX]t =[BAT]t or [BAB]t, K1 and K2 represent the equilibrium constants for
steps (i) and (ii) respectively, and k3 represents the specific reaction rate for the rate
Table 3. Activation Parameters for the Oxidation of Sugars by BAT and BAB at 30°C
d-Mannose
d-Glucose
d-Fructose
l-Arabinose
d-Ribose
Activation
Parameter
BAT BAB BAT BAB
BAT
84.7
BAB BAT BAB BAT BAB
Ea kJ molꢀ1 126
124
121
117
115
115
112
83.8 124
81.2 121
122
119
111
108
110
108
¼
DH kJ
molꢀ1
123
82.1
90.5
¼
DG kJ
molꢀ1
96.2 95.7 94.1 93.7
90.0 94.8 94.5 93.3 92.9
¼
DS JKꢀ1
molꢀ1
88.1 83.2 66.2 60.8 ꢀ 27.1 ꢀ 32.7 84.9 79.4 48.2 47.8
22.8 22.5 21.7 21.4 16.8 16.7 22.6 22.3 20.7 20.6
Log A
[BAT]o = [BAB]o = 2.00 ꢁ 10ꢀ3 M; [HOꢀ ] = 2.00 ꢁ 10ꢀ2 M; [S]0 = 3.00 ꢁ 10ꢀ2 M; I = 0.100 M.

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SHASHIKALA AND RANGAPPA
1.1
1
A-[D-Man]
B-[D-Glu]
C-[D-Fru]
D-[L-Ara]
E-[Rib]
a-[D-Man]
b-[D-Glu]
c-[D-Fru]
d-[L-Ara]
e-[Rib]
0.9
0.8
0.7
0.6
0.5
0.4
0
1
0.2
0.8
0.4
0.6
0.6
0.4
0.8
0.2
1
0[BAB]
`n'
Figure 3. Plots of koobs/konbs vs. ‘n’ in H2O–D2O mixtures; [S]o = 3.00 ꢁ 10ꢀ2 M, [BAT]o =
[BAB]o = 2.00 ꢁ 10ꢀ3 M, [HOꢀ ] = 2.00 ꢁ 10ꢀ2 M, temp = 30°C. A, B, C, D and E refer to BAT
and a, b, c, d and e refer to BAB.
limiting step. It is assumed that [H2O] > 1 +K2 [Eꢀ ] and the rate law Eq. 2 is reduced
to Eq. 3.
2
K1K2k3½SŠ½OXŠ ½HOꢀŠ
t
Rate ¼
ð3Þ
½H2OŠ
which agrees with the observed rate law, rate = kobs [S] [HO ꢀ ]2 [OX].
Table 4. Proton Inventory Studies for the Oxidation of Sugars by BAT and BAB in H2O–D2O
Mixtures at 30°C
104 kobs (sꢀ1
)
Atom Fraction
of Deuterium
(n)
d-Mannose
d-Glucose
d-Fructose
l-Arabinose
d-Ribose
BAT BAB BAT BAB BAT BAB BAT BAB BAT
BAB
0.000
0.250
0.500
0.750
0.930
1.32
1.51
1.72
2.01
2.44
1.73
1.96
2.34
2.86
3.46
3.58
4.36
4.97
5.80
6.82
4.37
5.21
6.12
7.20
8.40
16.8
20.0
23.5
26.2
31.3
20.2
24.2
28.5
33.3
38.4
2.51
3.91
3.31
4.02
5.27
2.74
3.08
3.64
4.38
5.80
6.74
7.92
9.48
6.24
7.14
8.44
9.98
13.7
5.71 12.4
[BAT]o = [BAB]o = 2.00 ꢁ 10ꢀ3 M; [S]o = 3.00 ꢁ 10ꢀ2 M; [HOꢀ ] = 2.00 ꢁ 10ꢀ2 M; I = 0.100 M.

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ERYTHRO-SERIES PENTOSES AND HEXOSES
227
Figure 4. HPLC analysis of the products formed by the oxidation of sugars by bromamines in
presence of NaOH at 30°C. 1. Glyceric acid; 2. erythronic acid; 3. Arabinonic acid; 4. ribonic
acid; 5 and 6. hexonic acids. Man, Glc, Fru, Ara and Rib, respectively, represent the reaction of
BAT or BAB with d-mannose, d-glucose, d-fructose, l-arabinose and d-ribose. The skewed
shoulder on the tailing edge of the peak 2 represent a small amount (2–4%) of threonic acid.
The following results support the above conclusion:
(i) For reaction involving a fast pre-equilibrium of H + or HOꢀ ion transfer, the
rate increases in deuterium oxide medium, because D3O+ is a stronger acid than H3O +
and DOꢀ is a stronger base than HOꢀ. Therefore, the observed increase of oxidation
rate in deuterium oxide agrees with the fast pre-equilibrium transfer of H + to HOꢀ
ion[15] (step i). The dependence of rate constant (konbs) on ‘n’ (n = the atom fraction of
deuterium oxide in a solvent mixture of water and deuterium oxide) is given by the
Gross–Butler[16,17] Eq. 4,
p
ð1 ꢀ n þ nFjÞ
TS
koobs=knobs
¼
ð4Þ
p
RSð1 ꢀ n þ nFjÞ

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228
SHASHIKALA AND RANGAPPA
Table 5. HPLC Analysis of the Products Formed by the Oxidation of Sugars by BAT and BAB
in Alkaline Medium
Products (Approximate Mole %)a
Mole of BAT or
BAB Consumed
per Mole of Sugar
Erythronic and
Threonic
Acid
Arabon Ribonic
Acid
Glyceric Hexonic
Acid
Sugar
Acid
Acid
d-Mannose
d-Glucose
d-Fructose
l-Arabinose
d-Ribose
2.50
2.80
2.90
2.20
1.70
36.0
35.0
30.0
28.0
30.0
19.0
21.0
20.0
8.00
8.00
35.0
36.0
40.0
49.0
48.0
4.00
3.00
8.00
14.0
14.0
6.00
5.00
4.00
–
–
a Based on the areas normalized using response factors obtained by analyzing standard aldonic
acid solutions.
where Fi and Fj are isotopic fractionation factors for the isotopically exchangeable
hydrogen sites in the transition state (TS) and reactant site (RS) respectively. If the
reaction proceeds through a single transition state, then Eq. 4 becomes Eq. 5.
koobs=konbs ¼ ½1 þ nðFj ꢀ 1ފ
ð5Þ
A comparison of the plots of konbs vs. ‘n’ (not shown) with the standard curves[18]
suggested a single proton exchange in the transition state. Furthermore, the plots of
(koobs/konbs) vs. ‘n’ (Figure 3) were linear with slopes (Fj ꢀ 1) from which Fj the
fractionation factor of HO ꢀ ion can be calculated. The Fj for the oxidation of erythro-
series sugars by BAT or BAB is about 0.5. Hence the formation of a single transition
state with the active participation of HOꢀ ion are indicated in the present studies.
(ii) Addition of methanol to the reaction mixture decreased the rate. The plots of
log kobs vs. 1/e were linear with negative slopes (Figure 2). Assuming a double sphere
model[17] for the reaction, the effects of solvent composition on the rate of a reaction
involving two negative ions are given by Eq. 6,
log k ¼ log ko ꢀ ZAZBe2=DKTdAB
ð6Þ
where ko is the rate constant in a medium of infinite dielectric constant, ZAe and ZBe
are the charges on the ions, dAB is the size of the activated complex, K is Boltz-
mann constant and T is absolute temperature. From the slopes of the straight lines, in
Figure 2 (slope = ꢀ ZAZBe2/KTdAB), dAB values are calculated. The values are 3.3 A,
˚
˚
˚
˚
˚
˚
˚
˚
˚
4.5 A, 4.8 A, 3.6 A and 4.6 A in the case of BAT and 2.8 A, 3.6 A, 4.1 A, 3.01 A and
˚
3.7 A in the case of BAB for d-mannose, d-glucose, d-fructose, l-arabinose, and
d-ribose, respectively. These values are comparable with those obtained for similar
reactions.[19]
(iii) Scheme 1 shows that the rate determining step, Eq. iii, involves interaction
between two negatively charged ions which requires a very high activation energy. The
observed high activation energies agree with this prediction (Table 3). Positive values of

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ERYTHRO-SERIES PENTOSES AND HEXOSES
229
¼
¼
DS and relatively high values of DH indicate more disorders in the transition state,
¼
and near constancy of DG values supports the proposed similar mechanism for the
oxidation of sugars.
The formation of pentonic acids and erythronic acid by the loss of one and two
carbon atoms, respectively, and minor proportions of hexonic acids suggested that these
sugars react with BAT or BAB mainly through keto-enolic intermediates. The for-
mations of only minor amounts of hexonic acids suggest that hexoses react extremely
slowly with BAT or BAB in the aldo-enolic forms. This conclusion agrees with the
formation of only a minor amount of mannonic acid despite the existence of a significant
amount of unreacted mannose in the aldose form even after 24 h of incubation with BAT
or BAB (Figure 4).
In contrast to hexoses, pentoses gave significant amounts of corresponding al-
donic acids (pentonic acids). From the product profiles, clearly, the major products are
formed by the cleavage of C-1–H and C-1–C-2 bonds. Furthermore, since erythro-
pentulose was not formed to a noticeable extent by the alkali-catalyzed tautomerization
of arabinose or ribose, this result together with the above data suggests that pentoses
undergo oxidation by BAT or BAB through aldo-enolic intermediates.
The negative entropy change for fructose demonstrates that fructose has a more
orderly structure in the transition state and is sterically favored for oxidation by BAT or
BAB. HPLC sugar profiles of the reaction mixture at various time points and product
profiles demonstrate that, in the case of aldo-hexoses, the fructose isomer formed by
the alkali-catalyzed isomerization is the species that reacts with BAT or BAB. The
observed faster reaction rate and lower activation energy for fructose (Tables 1 and 3)
compared with glucose and mannose agree with the above conclusion. Based on these
considerations, a plausible mechanism for the oxidation of sugars by BAT or BAB is
proposed in Scheme 2. This general mechanism accounts for the observed kinetics and
products of oxidation.
In the proposed mechanism (Scheme 2) the anion Eꢀ of sugars (keto-isomer in
the case of hexoses and aldo isomer in the case of pentoses) reacts with BAT or BAB
to form intermediates X1, X3. In the case of anions (Eꢀ ) from hexoses, the loss of
hydrogen occurs at either C-1 or C-3 to form C-1–C-2 or C-2–C-3 enediols containing
bromoxyl group at C-2. Since these enediols contain polarized double bonds, hydroxide
ion can add at C-2 to form intermediates X1 and X2. The formation of X2 accompanies
epimerization at C-2 and C-3, then X1 and X2 can undergo cleavage of C–C bonds
between C-1 and C-2, the former giving arabinonic acid and the latter forming a
mixture of arabinonic and ribonic acids. In the case of Eꢀ from pentoses, hydrogen can
be removed only from C-2 to form C-1–C-2 enediol anion, which in the presence of
alkali forms intermediate X3 with epimerization at C-2. Breakage of C-1–H bonds
from X3 gives a mixture of arabinonic and ribonic acids as in the case of X2. The
cleavage of C–C bonds between C-2 and C-3 in X1 and X2, and the breaking of C–C
bonds between C-1 and C-2 in X3 yield aldotetrose without epimerization at C-4
(hexoses) or at C-3 (pentoses). The aldotetrose further oxidizes to yield erythronic acid
and a minor proportion of threonic acid (Table 5). The reaction can proceed further,
with the cleavage of C–C bonds between C-3 and C-4 of hexoses and the breaking of
C–C bonds between C-2 and C-3 of pentoses, to form glyceric acid.
Since a common mechanism is operative, a comparison of the rates of oxidation
of sugars by BAT and BAB was desirable. If the values of standard rate constants

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SHASHIKALA AND RANGAPPA
OH
_
OH
OH
C
OH
OH
H_
C
H
O
N
_
_
COOH
_
H _
H
O
C H
H--OH
C
H
_
_
H
_
H
C
_
R
Br
_
C
=
HO C_O
HO-C-H
Br_
_ B
_
r
_
HO-C-H
_
C _ O _ Br
C _
O
H
C
_
OH
O
HO-C-H
H-C-OH
H-C-OH
H-C-OH
OH
+
HO-C-H
HO-C-H
H-C-OH
H-C-OH
_
HO-C-H
H-C-OH
2
-
Br
,
-
RN
H-C-OH
H-C-OH
H-C-OH_ C H
H-C-OH
OH
2
OH
CH
H-C-OH
2
H-C-OH
Arabinonic acid
C H OH
OH
CH OH
2
CH
OH
2
CH
2
CH
2
OH
2
Hexoses
X
1
Keto-enolic anion
(Fructose)
_
E
(
)
_
OH
R
_
N
OH
OH
OH
OH
_
H _C _
H
H_ _ H
C
H
C
H
CO OH
HO-C-H
H-C-OH
_
_
COOH
Br
H
C _
C
H
O
C
_ Br
_
_ O_ Br
C
_
O
HO
_
_
HO C O Br
H-C-OH
_
OH
HO
C
H _OH
H-C-OH
H-C-OH
HO-C-H
H-C-OH
HO
+
_
C
_
H-C-OH
H-C-OH
+
_
Br
,
H-C-OH
H-C-OH
OH
H-C-OH
H-C-OH
_ C H OH
2
H-C-OH
H-C-OH
H-C-OH
CH
_
2
CH
CH
OH
CH
OH
OH
CH OH
2
2
2
OH
CH
2
2
X
Ribonic acid Arabinonic acid
2
Keto-enolic anion
_
( E)
OH
H
COOH
H
H_ _ H
C
_
_
_
HO C O Br
H-C-OH
_
=
C O
_
_
_
HO
C
O Br
RNBr
,
OH
H-C-OH
H-C-OH
_
H-C-OH
H-C-OH
_
_
+
_
H
O OH
,
2
-
H C O
C
_
H
-
RN
,
Br
CHOH
2
OH,
2
_Br
H-C-OH
_CH
,
_
H-C-OH
+
CHOH
2
_
H-C-OH
H
,
CH OH
2
C HOH
2
Erythronic acid
Erythrose
X
and X
1
2
H
H
_
_ O_Br
HO
C
H
COOH
=
_
C
O
_
_
H
H C O
_
_
,
RN
OH
_Br
H-C-OH
RNBr
HO C O
H-C-OH
_
_
HCO O H
+
_
Br
H-C-OH
2
_
_
-
H-C-OH
H
,
+
OH
CH
-
_ Br
CH
OH
2
_H
,
2
C H OH
2
CHOH
2
Glyceric acid
_
N
H
H
C
H
H
CO OH
HO-C-H
R
2
H
CO OH
Br
_
O
_
_
O
_
_
_
_
_
_
C
HO C_
Br
Br
_
_
C =O
_
H
O
_
C
Br
O
O
H
C
OH
_
OH
_
OH
HO H
_
H
C
OH
HO-C-H
C_ OH
H-C-OH
+
H-C-OH
H-C-OH
C
OH
+
_
H-C-OH
H-C-OH
_
_
+
_Br
H
_
H
C
C
O
_
H
,
H-C-OH
H-C-OH
_
H-C-OH
H-C-OH
H-C-OH
H-C-OH
_
_
RN
H-C-OH
H-C-OH
CH
OH
H
OH
CH
CH OH
CH OH
2
2
2
CH OH
CH OH
OH
CH
Arabinonic
2
Ribonic
acid
2
2
OH
Pentoses
(Ribose)
2
acid
Keto-enolic
anion ( E )
X
3
H
_
_
H
C_ O_
HO
H_
Br
_
CO OH
C= O
COO
_
_
H
_O
H
-
C
_
RNBr OH
H-C-OH
H-C-OH
,
H C OH
H-C-OH
H-C-OH
H-C-OH
_
Br
COO H
+
_
-
2
OH
CH
2
H-C-OH
-
RN
_
CH OH
CH OH
CH OH
2
2
2
Glyceric acid
Erythronic acid
X
3
Erythrose
Scheme 2. Reaction mechanism scheme.

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ERYTHRO-SERIES PENTOSES AND HEXOSES
231
(kobs) are taken into consideration (Table 1), then d-fructose and d-ribose have the
highest rates while d-mannose and l-arabinose react slowly among the the two classes
of sugars hexoses and pentoses, respectively. Isbell and coworkers[20] in their tritium
exchange experiments observed the rate sequence ribose >lyxose> xylose > arabinose.
Dewit et al.[21] studied the behavior of monosaccharides in aqueous alkaline solution
through UV absorption spectroscopy, by monitoring the band at 310 nm. The rates of
enediol formation are xylose >arabinose> ribose. Gleason and Barker[22] noted that the
rates of oxidation of pentoses by oxygen in presence of alkali are dependent on the
medium. In dilute KOH solution, the relative rate was, xylose > ribose >arabinose >
lyxose, while in the presence of concentrated alkali it was ribose >lyxose >xylose>ar-
abinose. However, using the pk values of the pentoses, relative rates for the oxidation
a
of pentoses, were calculated as xylose > ribose > lyxose > arabinose. The difference found
between this work and the rate sequences reported by other workers could possibly
be due to the formation of 1,2-enediols either in the E or Z forms. Isbell and co-
workers[20] proposed that aldoses and ketoses generally yield mixtures of Z and E
enediols, the proportion of which differs from sugar to sugar. We believe that the trend
reflects the probability of E enediol formation, which is more stable than the Z isomer.
The probability is greatest with d-ribose while d-mannose has the least tendency to
form the trans isomer. It appears in general that, the probability of E enediol formation
in the case of pentoses is greater than that of hexoses with the exception of d-glucose.
Earlier studies on the oxidation of hexoses and pentoses by CAT and CAB in
alkaline medium[6,7] showed the experimental rate law, rate = k [OX] [S] [HOꢀ ]2,
which amounts to the involvement of oxidant in a rate limiting step. Substantial
primary salt, solvent isotope, ionic strength and dielectric effects were noticed.
However, in the present studies it was observed that oxidation was generally faster with
the bromine analogues.[23,24] This result has been rationalized in terms of the
differences in electrophilicity of halonium cations, Cl + and Br + which are generally
the reactive species in these reactions.[25] Also, it is partly due to the moderate dif-
ferences in the van der Waal’s radii of bromine and chlorine.
EXPERIMENTAL
Materials and Methods. d-mannose, d-glucose, d-fructose, l-arabinose and d-ribose
were purchased from Sigma chemicals. BAT and BAB were prepared by the method of
Nair et al.[26] The aqueous solutions of BAT and BAB were prepared, iodometrically
standardized, and stored in brown bottles to prevent their photochemical deterioration.
A concentrated aqueous solution of sodium perchlorate was used to maintain the
ionic strength of the reaction mixture. All other chemicals used were of analytical
grades of purity. Triply distilled water was used for preparing aqueous solutions. The
solvent isotope studies were made with D2O (99.4%) supplied by Bhabha Atomic Re-
search Center, Bombay (India).
Kinetic Procedure. The reactions were carried in glass stoppered pyrex boiling
tubes coated black on the outside. Pseudo first order conditions of [sugar]o ꢂ[oxidant]o
were maintained for kinetic runs (oxidant = BAT or BAB). The oxidant and the
requisite amounts of sugar, alkali, sodium perchlorate solutions and water (for constant

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232
SHASHIKALA AND RANGAPPA
total volume) were taken in separate boiling tubes and thermostated for 30 min at 30°C.
The reaction was initiated by the rapid addition of oxidant (BAT or BAB) to the
mixture and its progress was monitored by iodometric estimation of unconsumed oxi-
dant in known aliquots of the reaction mixture at regular intervals of time. The reaction
was studied for more than two half lives. Pseudo first order rate constants kobs were
calculated from the plots of log [OX]o vs. time, where OX represent the oxidant and
these were reproducible within 5% error.
Stoichiometry and Product Analysis. The reaction mixture containing 0.01M sugar,
0.02M alkali, and an excess of oxidant (BAT or BAB ꢃ 0.05M) was kept for 24 h at
30°C. The unconsumed oxidant (BAT or BAB) was determined iodometrically. From
these data, the amount of the oxidant consumed per mole of sugar was found to be 3
moles for hexoses and 2 moles for pentoses.
The oxidation products were analyzed by Dionex HPLC (high performance liquid
chromatography) with pulsed amperometric detection using a Carbopac PA1 high-pH
anion exchange column (4 ꢁ 250 mm)[27] Isocratic elution with 0.2 M NaOH was used.
The products arabonic, ribonic, erythronic, threonic, glyceric and hexonic acids were
identified by comparison of the HPLC retention times with those of standard aldonic
acids and by GLC-MS.
For GLC-MS characterization, the reaction mixture was extracted with diethyl
ether to remove p-toluenesulphonamide and then passed through AG 50 W-X12 (H + )
and AG-4-X4 (base) resins. The AG 4-X4 resins were eluted with 1M pyridine-1M
acetic acid, pH 5.2, and lyophilized. The products were converted into their trime-
thylsilyl derivatives and then analyzed by GLC-MS (Chart speed = 0.5 mm/min and
flow rate = 0.8 ml/min).
ACKNOWLEDGMENTS
One of the authors (KSR) thanks the Department of Science and Technology
(DST), New Delhi, for financial support. V.S. is grateful to the A.V.K. College,
Hassan and University Grants Commission, New Delhi, India, for awarding the Teach-
er Fellowship.
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ERYTHRO-SERIES PENTOSES AND HEXOSES
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Received July 19, 2001
Accepted February 5, 2002