Osmium(VIII)-catalyzed oxidation of some cyclic amines by potassium hexacyanoferrate(III) in alkaline media: A kinetics and mechanistic study

Article abstract of DOI:10.1023/A:1024765330259

Reactions of morpholine, piperidine, and piperazine with Os(VIII) -catalyzed hexacyanoferrate(III) in alkaline media to produce the corresponding lactam have been studied at constant temperature and ionic strength. The reactions followed first-order kinetics with respect to [amine] and [Os(VIII)] but were independent of [Fe(CN)₆^3-] and [OH^-]. The effects of introduced electrolytes, potassium hexacyanoferrate(II), relative permitivity, and temperature have also been studied. A mechanism accounting for these results has been proposed.

Full text of DOI:10.1023/A:1024765330259

Chemistry of Heterocyclic Compounds, Vol. 39, No. 4, 2003
OSMIUM(VIII)-CATALYZED OXIDATION
OF SOME CYCLIC AMINES BY POTASSIUM
HEXACYANOFERRATE(III) IN ALKALINE MEDIA:
A KINETICS AND MECHANISTIC STUDY
M. M. Al-Subu1, W. J. Jondi1, A. A. Amer1, M. Hannoun1, and M. J. Musmar2
Reactions of morpholine, piperidine, and piperazine with Os(VIII)-catalyzed hexacyanoferrate(III) in
alkaline media to produce the corresponding lactam have been studied at constant temperature and
ionic strength. The reactions followed first-order kinetics with respect to [amine] and [Os(VIII)] but
3–
were independent of [Fe(CN)6 ] and [OH–]. The effects of introduced electrolytes, potassium
hexacyanoferrate(II), relative permitivity, and temperature have also been studied. A mechanism
accounting for these results has been proposed.
Keywords: morpholine, piperidine, piperazine, Os(VIII), hexacyanoferrate(III), lactam, kinetics,
oxidation.
The use of oxidizing agents in attacking particular groups in simple and large organic molecules has
received great attention [1, 2]. Among these is potassium hexacyanoferrate(III) [3-7], a one-electron oxidant
with a redox potential of 0.36 V. Although hexacyanoferrate(III) has some advantages that make it suitable for
the oxidation of several organic substrates [8, 9], in particular its stability over the entire pH scale and its being
a moderate oxidant, its reactions with some nitrogen-containing compounds are not facile and require the
presence of a catalyst [10, 11]. The present work aimed to investigate the suitability of employing Os(VIII) as a
3-
catalyst in the oxidation of some six-membered cyclic amines by alkaline Fe(CN)6 . Furthermore, the effect of
the atom occupying position 4 in the cyclic amine molecule will be explored.
MATERIALS AND METHODS
Reagents. Potassium hexacyanoferrate(III), piperidine, and metal halides (Riedel-deHaen), morpholine,
piperazine, and K4Fe(CN)6 (Merck), and OsO4 (Sigma) were used in the purest form available without further
purification. Deionized distilled water was used for the preparation and dilution of all solutions. The desired
hydroxide ion concentration was achieved using prestandardized NaOH solution. The required ionic strength
was achieved by adding NaCl. The reactions were initiated by simultaneous addition of the required volume of
K3Fe(CN)6 and the amine solutions to keep the total volume constant in all runs.
__________________________________________________________________________________________
1 Department of Chemistry, An-Najah National University, Nablus, Palestinian autonomy, Israel; e-mail:
alsubu@najah.edu. 2 College of Pharmacy, An-Najah National University, Nablus, Palestinian autonomy, Israel.
Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 559-565, April, 2003. Original article
submitted March 27, 2002.
478
0009-3122/03/3904-0478$25.00©2003 Plenum Publishing Corporation

Kinetics Studies. The kinetics were studied by measuring the absorbance of the unreacted K3Fe(CN)6,
at 414 nm, by transferring some of the reaction mixture, within 20-25 s, into the thermostated cell of the
spectrophotometer. The absorbance was recorded at appropriate intervals for more than four half-lives.
Stoichiometry. The stoichiometry of the reactions was determined by reacting the corresponding amine
(1.0 × 10-4 mol·dm-3) with Fe(CN)63- (1.00 × 10-3 mol·dm-3) for 96 h to ensure complete reaction as indicated by
3-
the constant absorbance of Fe(CN)6 . The [OH-] was kept constant at 0.100 mol·dm-3 and the temperature at
3-
308 K; the concentration of OsO4 was also kept constant at 1.0 × 10-5 mol·dm-3. The consumed Fe(CN)6 was
found to be (4.0 to 4.2) × 10-4 mol·dm-3 for the case of morpholine and piperidine, and about 2.0 × 10-4 mol·dm-3
3-
for the case of piperazine. The presence or absence of OsO4 has no effect on the total consumption of Fe(CN)6 .
Product Analysis. A known amount of the amine was placed in a flask, and a tenfold excess of
3-
Fe(CN)6 and the required amount of OH- were added. The resulting solution was shaken and kept for 96 h to
ensure completion of the reaction. The precipitate was filtered off and the organic material was extracted from
the mixture by chloroform (4 × 60 ml). The chloroform solution was evaporated to a small volume, until the
organic material precipitated. The products, 2-morpholinone, 2-piperidinone, and 2,5-piperazinedione, were
identified by comparison of their IR spectra, obtained by a Pye Unicam Sp200 spectrometer, and the mass
spectra, obtained at the Midwest Center for Mass Spectroscopy at the University of Nebraska-Lincoln, with
those of authentic samples.
RESULTS AND DISCUSSION
The stoichiometric analysis showed that 1 mol of the amine consumes 4 mol of Fe(CN)63- regardless of
the presence of OsO4. This indicates that OsO4 has no effect on the final outcome. Furthermore, product analysis
3-
showed that the products of the catalyzed and uncatalyzed reactions of Fe(CN)6 with morpholine, piperidine,
and piperazine were 2-morpholinone, 2-piperidinone, and 2,5-piperazinedione, respectively. Accordingly, the
overall balanced equations can be written as
O
O
4OH–
4Fe(CN)6
4–
4–
3–
(1)
3H2O
4Fe(CN)6
+
+
+
+
+
+
+
N
H
N
H
O
4OH–
3–
4Fe(CN)6
(2)
3H2O
4Fe(CN)6
+
N
H
O
O
N
H
H
N
H
N
O
3–
4–
8OH–
8Fe(CN)6
8Fe(CN)6
+
6H2O (3)
+
+
+
N
H
N
H
The relative reactivity of the amines toward hexacyanoferrate(III), as indicated by the initial rate values,
followed the order piperidine > piperazine >> morpholine.
3-
The effect of [OsO4] on the reaction rate of the amines with Fe(CN)6 is shown in Table 1. Plots of
-log[initial rate] versus -log[OsO4] indicate that the reaction order with respect to [OsO4] is 1.0 ± 0.1 in all cases.
Species such as OsO4, [OsO4 (H2O)2], [OsO4 (H2O) (OH)]-, and [OsO4 (OH)2]2- coexist in fast equilibria
with each other, as different forms of Os(VIII), in basic medium [12]. Since the present reaction medium is
strongly basic, the total [Os(VIII)] can be assumed to be [OsO4(OH)2]2- [4].
479

TABLE 1. Dependence of Initial Rate on Initial [Os(VIII)]
103[initial rate], mol·dm-3·s-1
piperidine
105 [Os(VIII)],
mol·dm-3
morpholine
piperazine
1.00
2.00
3.00
4.00
5.00
6.00
1.73
3.50
5.15
6.90
8.60
9.95
2.77
5.33
8.31
10.45
13.10
15.98
2.05
4.00
5.98
7.90
9.98
12.04
_______
3-
103 [Fe(CN)6 ] = 1.00, 10 [amine] = 1.00, 10 [OH-] = 1.00 mol·dm-3,
temp. 35°C, and 10µ = 1.5 mol·dm-3.
3-
The orders with respect to [amine] (Table 2) and [Fe(CN)6 ] (Table 3) were 1.0 ± 0.15 and 0.0 ± 0.1
respectively. Similar results were reported for the oxidation of carbonyl compounds with Fe(CN)63- catalyzed by
Os(VIII) [3, 4]. The nearly zero-order effect of the hydroxyl ion (Table 4) is acceptable as a result of its
relatively high concentration (0.10 mol dm-3) relative to [Os(VIII)] (1.0 × 10-5 mol dm-3). Moreover, the
hydroxyl ion may not act as free OH- but as a part of the [Os(VIII)] complex. Addition of Fe(CN)64- retarded the
TABLE 2. Dependence of Initial Rate on Initial [Amine]
103 [initial rate], mol·dm-3·s-1
10 [amine], mol·dm-3
morpholine
piperidine
piperazine
1.00
1.50
2.00
3.00
4.00
6.00
1.73
2.46
3.33
4.90
6.66
9.52
2.77
3.72
5.12
7.75
10.10
15.15
2.05
3.01
3.98
5.95
7.88
10.20
_______
3-
103 [Fe (CN)6 ] = 1.00, 10 [OH-] = 1.00, 105 [Os(VIII)] = 1.00 mol·dm-3,
temp. 35°C and 10µ = 1.5 mol·dm-3.
3-
TABLE 3. Dependence of Initial Rate on Initial [Fe(CN)6 ]
103 [initial rate], mol·dm-3·s-1
piperidine
103 [Fe(CN)63-],
mol·dm-3
morpholine
piperazine
0.40
0.60
0.80
1.00
1.20
1.55
1.60
1.64
1.73
1.73
2.70
2.73
2.74
2.77
2.80
1.95
1.95
1.98
2.05
2.05
_______
10 [amine] = 1.00, 10 [OH-] = 1.00, 105 [ Os(VIII)] = 1.00 mol·dm-3,
temp. 35°C and 10µ = 1.5 mol·dm-3.
480

reaction rate (Table 5 and Fig. 1). This indicates that Fe(CN)64- is involved in a reversible step that could affect
the rate-determining step. Addition of different potassium salts to maintain a constant ionic strength had no
effect (within experimental error) on the reaction rates for all amines (Table 6).
TABLE 4. Dependence of Initial Rate on Initial [OH–]
103 [initial rate], mol·dm-3·s-1
102 [OH-], mol·dm-3
morpholine
piperidine
piperazine
0.40
1.00
2.00
3.10
5.00
10.00
0.90
1.15
1.22
1.31
1.45
1.73
2.31
2.42
2.51
2.60
2.65
2.77
1.01
1.21
1.45
1.68
1.98
2.05
_______
3-
103 [Fe(CN)6 ] = 1.00, 10 [amine] = 1.00, 105 [Os(VIII)] = 1.00,
10 [OH-] = 1.00 mol·dm-3, temp. 35°C and 10µ = 1.5 mol·dm-3.
4-
TABLE 5. Dependence of Initial Rate on Added [Fe(CN)6 ]
103 [ initial rate], mol·dm-3 s-1
piperidine
103 [Fe(CN)64-],
mol·dm-3
morpholine
piperazine
0.1
0.4
0.7
1.0
2.0
3.0
1.14
1.05
0.98
0.69
0.60
0.52
2.08
1.96
1.85
1.78
1.72
1.62
1.09
0.92
0.66
0.64
0.31
0.27
_______
3-
103 [Fe (CN)6 ] = 1.00, 10 [amine] = 1.00, 105 [Os(VIII)] = 1.00,
10 [OH-] = 1.00 mol·dm-3, temp. 35°C and 10µ = 1.5 mol·dm-3.
TABLE 6. Dependence of Initial Rate on Different Electrolytic Salts
103 [initial rate], mol·dm-3·s-1
Salt
morpholine
piperidine
piperazine
KF
KCl
KBr
KI
KNO3
NaCl
NH4Cl
1.70
1.65
1.65
1.63
1.64
1.68
1.19
2.95
2.98
2.95
2.95
2.97
2.90
2.20
2.05
2.07
2.10
2.09
2.10
2.00
1.30
_______
3-
102 [salt] = 3.50, 10 [amine] = 1.00, 103 [Fe(CN)6 ] = 1.00, 105 [Os(VIII)] =
= 1.00, 10 [OH-] = 1.00 mol·dm-3, temp. 35°C and 10µ = 1.5 mol·dm-3.
481

103 [Fe(CN)64-] mol·dm-3
Fig. 1. Effect of potassium hexacyanoferrate(II) on the rate of oxidation of piperidine (1),
morpholine (2), and piperazine (3) at 35°C.
Addition of chlorides showed that sodium and potassium cations have no specific effect on rate,
whereas ammonium has. Being acidic, ammonium ion consumes some OH- and thus affects the production of
the assumed active form of the catalyst [OsO4(OH)2]2-. The resulting ammonia could also inhibit the reaction
through the formation of a complex with Os(VIII), say, [OsO4(NH3)2].
Added ethanol retarded the oxidation of morpholine but not that of piperazine or piperidine (Table 7).
This could be due to solvation of the oxygen atom occupying position 4 in the morpholine ring.
The activation parameters were obtained by carrying out the reactions at temperatures 299, 304, 309 and
314 K. Rate constants and activation parameters were calculated (Table 8) using the rate equation (Eq. (4)) and
≠
standard relations such as Arrhenius and Gibbs free energy [13]. ∆S has relatively high negative values
-1
-1
3-
≠
comparable to that reported for the oxidation of benzaldehyde (∆S = -163.75 J·mol ·K ) by Fe(CN)6
catalyzed by Os(VIII) [4]. This indicates that the complexes formed in the present work are of the same type and
the same degree of order as that reported for benzaldehyde.
TABLE 7. Dependence of Initial Rate on % Ethanol
103 [initial rate], mol·dm-3·s-1
% Ethanol (v/v)
morpholine
piperidine
piperazine
0.0
10.0
20.0
30.0
40.0
50.0
1.73
1.50
1.29
0.98
0.82
0.71
2.77
2.73
2.70
2.68
2.68
2.65
2.05
2.08
2.10
2.11
2.12
2.15
_______
3-
103 [Fe(CN)6 ] = 1.00, 10 [amine] = 1.00, 105 [Os(VIII)] = 1.00, 10 [OH-] =
1.00 mol·dm-3, temp. 35°C and 10µ = 1.5 mol·dm-3.
TABLE 8. Activation Parameters
Compound
Ea, kJ·mol-1
S≠ , J·mol-1·K-1
H≠, kJ·mol-1
G≠ , kJ·mol-1
∆
∆
∆
Morpholine
Piperidine
Piperazine
14.80
34.86
23.28
-238.9
-166.4
-151.7
12.20
32.27
20.69
86.24
83.64
67.55
482

The above results suggest an experimental rate law for the initial rate, which can be written as
3-
-d [Fe(CN)6 ] /dt = k [amine] [Os(VIII)]
(4)
Considering the equilibria (5) and (6) for osmium tetroxide in aqueous solution, the following
2-
mechanism presented in Eq. (7)-(12) has been suggested, assuming the active form of Os(VIII) is OsO4(OH)2 :
OsO4(OH)22- (K1 = 5.5 × 1013 and K2 = 24±4) and X = O, CH2, NH.
K1
[OsO4(OH)(H2O)]– + H2O
(5)
(6)
[OsO4(H2O)2]
+
OH–
K2
[OsO4(OH)2]2–
+
H2O
[OsO4(OH)(H2O)]– + OH–
[OsO4(OH)2]2– + C4H9NX
β
[OsO4(OH)2C4H9NX]2–
(7)
I
k
[OsO4(H2O)2]2– + C4H7NX
(8)
(9)
[OsO4(OH)2C4H9NX)]2–
2[Fe(CN)6]3– + [OsO4(H2O)2]2–
2[Fe(CN)6]4– + [OsO4(H2O)2]
[OsO4(OH)2C4H7NX]2–
[OsO4(OH)2]2– + C4H7NX
[OsO4(OH)2C4H7NX]2–
(10)
II
[OsO4(H2O)2]2– + C4H7NXO
(11)
(12)
2[Fe(CN)6]3– + [OsO4(H2O)2]2–
2[Fe(CN)6]4– + [OsO4(H2O)2]
The formation of a complex between Os(VIII) and benzaldehyde was proposed and supported by
Michaelis–Menten type of [initial rate]-1 versus [carbonyl]-1 plots [4] and agrees well with other reported
structures [14, 15]. Therefore complexes such as I and II are expected to be more stable and easier to obtain
from the reaction of Os(VIII) with amines than with benzaldehyde. This is also indicated by the initial rates,
obtained which are of the order of 10-3, while those of benzaldehyde were of the order of 10-7.
The formation and decomposition of the Os(VIII)–enamine transient complex (II) (Eqs. (10) and (11)) is
expected to be faster than the formation and decomposition of the Os(VIII)–amine transient complex (I) (Eqs.
(7) and (8)) as a result of the presence of the double bond in the former case. Therefore, the step desribed by
Eqs. (11) is assumed to be relatively fast and has no effect on the total rate of the reaction.
The reactivity order of the amines (piperidine > piperazine > morpholine) is in reverse to the
electronegativity trend of the atoms occupying positions 4 (C < N < O). Electron-withdrawing groups, through
the inductive effect, are expected to destabilize the iminium cation and the subsequent carbonium ion formed as
a result of the transfer of the first and second electrons, respectively, from Os(VIII) to the amine in the transient
complex (I) before it splits to give the product.
The above mechanism explains also the effect of ethanol on the oxidation of morpholine. Solvation of
morpholine will hinder the formation of complex (I) (Eq. (7)), and thus slow down the reaction.
The effect of potassium ferrocyanide can be seen from Eq. (9). [Fe(CN)6]4- is expected to retard the
regeneration of Os(VIII) from Os(VI) and [Fe(CN)6]3-, and consequently slows down the reaction.
The above mechanism enables us to derive the following rate law:
3-
2-
-d [Fe(CN)6 ] / dt = k0 [OsO4(OH)2 ]·[amine]
which is in agreement with the experimental results.
(13)
483

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