Kinetic and mechanistic study of N-aminopiperidine formation via the raschig process

Article abstract of DOI:10.1134/S0023158413060037

Formation of N-aminopiperidine (NAPP) in the reaction of monochloramine with piperidine was studied by varying the reagents concentrations, pH and temperature. The study was carried out in diluted solutions, recording simultaneously monochloramine concentration by UV spectrophotometry at 243 nm and hydrazine concentration at 237 nm after treatment with formaldehyde. The presence of two competitive reactions: formation of NAPP and a complex parallel reaction limiting the yield of hydrazine, was established. Reaction products were characterized by GC/MS analysis. The rate constant of NAPP formation and activation parameters were determined, k₁ = 56 × 10 ^-3 M^-1 s^-1 (25°C) and k₁ = 9.3 × 10⁶ exp(-46.5/RT) M^-1 s^-1, respectively. Pleiades Publishing, Ltd., 2013.

Full text of DOI:10.1134/S0023158413060037

ISSN 0023ꢀ1584, Kinetics and Catalysis, 2013, Vol. 54, No. 6, pp. 649–655. © Pleiades Publishing, Ltd., 2013.
Kinetic and Mechanistic Study of
NꢀAminopiperidine Formation
via the Raschig Process1
C. Darwich, M. Elkhatib, V. Pasquet*, and H. Delalu
Laboratoire Hydrazines et Composés Energétiques Polyazotés, Université Claude Bernard Lyon 1, France
*eꢀmail: veronique.pasquet@univꢀlyon1.fr
Received February 6, 2012
Abstract—Formation of Nꢀaminopiperidine (NAPP) in the reaction of monochloramine with piperidine was
studied by varying the reagents concentrations, pH and temperature. The study was carried out in diluted soluꢀ
tions, recording simultaneously monochloramine concentration by UV spectrophotometry at 243 nm and
hydrazine concentration at 237 nm after treatment with formaldehyde. The presence of two competitive reacꢀ
tions: formation of NAPP and a complex parallel reaction limiting the yield of hydrazine, was established. Reacꢀ
tion products were characterized by GC/MS analysis. The rate constant of NAPP formation and activation
parameters were determined,
tively.
k1 = 56 × °C) and k1 = 9.3 ×
10–3 M–1 s–1 (25 106 exp(–46.5/RT) M–1 s–1, respecꢀ
DOI: 10.1134/S0023158413060037
1
N
ꢀAminopiperidine (NAPP) is currently used [1, which imposes nonꢀstoichiometric conditions at all
stages of the synthesis.
2] as a precursor in pharmaceutical, cosmetics and
photographic industries and also for plant protection.
It is a component of drugs used particularly for smokꢀ
ing cessation and obesity. Moreover, NAPP has appliꢀ
cations in the field of crop protection where it is used
to prepare herbicide derived from tetrazolinone. Other
uses are reported [3]: manufacture of paper and transꢀ
parent film recording, elaboration of inhibitor gels and
resistant to amineꢀbased solvent.
The Raschig process is represented by the two folꢀ
lowing basic steps: (i) monochloramine (NH2Cl) forꢀ
mation
NH3 + OCl− ⎯⎯→NH2Cl + OH−
and (ii) hydrazine formation
R1R2NH + NH2Cl + OH−
⎯⎯→R1R2NNH2 + H2O + Cl−.
The methods for NAPP synthesis described in the
literature are essentially based on the use of urea [4–6]
or nitrosamines [7–17]. The first method, requiring
several steps, is not compatible with a continuous proꢀ
cess, the second one presents a great toxicity due to the
carcinogenic effect of nitrosamines, and hence
becomes a problem for industrialization. In our laboꢀ
ratory, another way has been developed: the reaction of
Despite its disadvantages, the Raschig process remains
the most economical method and lends itself to the
development of a continuous industrial process [19].
This challenge needs a thorough study of each step
of the basic and sideꢀreactions. The study of the oxiꢀ
dation of NAPP with monochloramine [20] and
the chlorine atom transfer reaction between
monochloramine and piperidine [21], which is one of
the principal sideꢀreactions observed in the synthesis
of NAPP via the Raschig process, are already pubꢀ
lished. In this paper, we report a kinetic and mechanisꢀ
tic study of NAPP formation via the monochloramꢀ
ine–piperidine interaction.
hydroxylamineꢀOꢀsulfonic acid (HOSA) with piperiꢀ
dine [18]. The first results are promising. However, it
presents some disadvantages related to the instability
of HOSA that leads to many sideꢀreactions and lowers
the yield.
Another way is the Raschig process. This is a selecꢀ
tive synthesis using neither organic solvent nor pollutꢀ
ing reagents. Moreover, contrary to the reaction with
participation of HOSA, it is particularly suitable for
continuous industrial process. However, it has disadꢀ
vantages related to low hydrazine content in the synꢀ
thesis solutions due to the high dilution of the reagents
and to the existence of numerous sideꢀreactions,
EXPERIMENTAL
Reagents and Apparatus
All the reagents and salts used were reagent grade
products from “Aldrich” and “Prolabo RP.” Water was
passed through an ionꢀexchange resin, then distilled
twice, deoxygenated, and stored under nitrogen.
Monochloramine is unstable in water and was thereꢀ
1
The article is published in the original.
fore prepared in situ at –10°C in reaction of sodium
649

650
DARWICH et al.
hypochlorite (2 M, 25 mL) and with NH3/NH4Cl XDB–C8 column (dP = 5
μ
m) using MeOH/H2O
aqueous solution ([NH4Cl] = 2.3 M, [NH3] = 3.6 M,
20 mL) in the presence of diethyl ether (40 mL). The
organic layer (0.8–1.0 M NH2Cl) was shaken and
washed several times with aliquots of distilled water.
Aqueous solution of monochloramine was obtained by
reꢀextraction from the ethereal phase.
The apparatus used for NAPP synthesis consisted
of two thermostated vessels, one on the top of the other
and joined by a conical fitting. The lower reactor
(70/30) as mobile phase (rate flow = 0.5 mL/min).
The monochloramine concentration was determined
with the use of previous calibration of column by stanꢀ
dard solutions of NH2Cl iodometrically titrated.
Concentrations of NAPP formed was also followed
by UV after derivation by the method developed in our
laboratory [22]: NAPP itself is transparent to UV in
the studied range (220–350 nm), therefore aliquots
were treated with formaldehyde (40ꢀfold excess) in
order to convert NAPP into its hydrazone (FNAPP),
which has an absorption maximum in UV at 237 nm
(
200 cm3) contained a magnetic stirrer and had inlets
to allow pH and temperature measurements, the
influx of circulating nitrogen and the removal of aliꢀ
quots for analysis. Because of the sensitivity of hydraꢀ
zine to oxidation upon exposure to air, the mixture was
monitored by an oxygenꢀsensitive electrode conꢀ
nected to a numerical indicator. The upper cylindrical
vessel (100 cm3) had a temperature sensor. It was
blocked at its base by a large diameter needle valve
integrated in the thermoꢀstated jacket. This setup
allowed rapid introduction of the ampoule contents
into the reactor and therefore precise definition of the
start of the reaction. A slightly reduced pressure was
maintained throughout the reaction mixture and the
temperatures of the two vessels were defined to
(
εFNAPP = 4485 M–1 cm–1).
GC/MS analyses were carried out on a chromatoꢀ
graph coupled to a mass spectrometer HP 5970
equipped with a CP–Sil C19 column (30 m, 250
i.d., f = 1.5 ), oven temperature rising from 30 up
to 200 with a heating rate of C/min. Methodꢀ
μ
m
d
μ
m
°
C
5°
ological details on the apparatus and the experimental
procedure have been described elsewhere [23, 24].
RESULTS AND DISCUSSION
Kinetic Study of the Monochloramine–Piperidine
Interaction
0.1°C.
Rate laws. The rate of the NAPP formation is
expressed by the following relation:
Reaction Conditions
d[NAPP]
α
β
(1)
v1 =
where k1
= k1[NH2Cl] [PP] ,
The reaction of NAPP formation was carried out in
alkaline medium, at pH 12.89 ([NaOH] = 0.1 M) and
dt
β
,
α
and
are the rate constant of NAPP forꢀ
mation and partial reaction orders, respectively.
In order to determine partial orders and rate conꢀ
stant, we have measured the instantaneous evolution
of chloramine and NAPP concentrations. Figure 1a
shows the successive UV spectra recorded at different
times. The evolution of the spectra is intricate and
involves several steps: during the first step, the
chloramine absorption at 243 nm decreases and shifts
toward higher wavelengths. At the same time, an isosꢀ
bestic point at 277 nm appears (Fig. 1b). During the
final step, a new absorption peak appears, increases
slowly, and shifts toward the lower wavelengths and
then stabilizes at 237 nm (Fig. 1a).
T
= 25°C. In order to minimize sideꢀreactions [20],
piperidine (PP) was used in excess with respect to
PP
[
]
chloramine (1.5
≤
≤
45). Concentrations of
NH Cl
[
]
2
reagents ranged between
1
×
10–3 and 10–2 M.
9
×
Procedure and Analysis
Piperidine was dissolved in deoxygenated water
and introduced into the lower reactor. The pH value
was adjusted by addition of sodium hydroxide and/or
a buffer solution. When thermal equilibrium was
reached, the aqueous solution of monochloramine of
identical pH was added from the upper vessel.
The concentration of monochloramine was moniꢀ
tored at 243 nm, the maximum of its ultraviolet
absorption (
(ε
These results show that it is not possible to follow
directly monochloramine concentration up to the end
of the reaction because of the interference of these sevꢀ
eral steps. Hence, in order to determine the rate laws,
= 458 M–1 cm–1), either by UV a method based on the use of the isosbestic point and
NH2Cl
concentration–time curves was established, limiting
the measurements to the half time of the reaction.
The presence of an isosbestic point requires a
spectrophotometry using a Cary 1E doubleꢀbeam
spectrophotometer or by HPLC using a HP 1100
chromatograph equipped with a Diode Array Detecꢀ
tor. As PP is not transparent in the UV spectral range defined stoichiometry between two chromogenic
and was present in excess in the reaction medium, the compounds, monochloramine and its instantaneous
reference cell in the experiments monitored by UV product. It excludes any subsequent slow reaction
spectrophotometry was filled with a PP aqueous soluꢀ involving one of the two compounds. This result is surꢀ
tion of identical concentration and pH as the reaction prising as the expected product, i. e. NAPP
medium. For experiments monitored by HPLC, the
(
C5H10NNH2) does not show any absorption in the
separation was carried out on a 150 mm ODS UV range under study. It cannot be an intermediate
×
3
KINETICS AND CATALYSIS Vol. 54
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2013

KINETIC AND MECHANISTIC STUDY OF
N
ꢀAMINOPIPERIDINE FORMATION
651
compound between NH2Cl and hydrazine because of
the immediate formation of the latter. The isosbestic
point can only be due to a parallel or competitive
reaction between the same reagents giving a chroꢀ
mophore P:
A
(a)
0.9
0.8
0.7
0.6
0.5
0.4
0.3
0.2
0.1
0
t
= 0
k1
End of the reaction
NH2Cl +
NH
+ HCl,
⎯⎯→
NNH2
k2
NH2Cl +
P +
⎯⎯⎯→
NH
Pi.
∑
i
Under these conditions, the absorbance of the reacꢀ
t
= 9.25 min
tion medium at any wavelength
lows ( = 1 cm):
λ
can be written as folꢀ
l
λ
λ
220 240 260 280 300 320 340
(2)
A = εNH Cl[NH2Cl] + εP[P].
λ
2
(b)
0.9
1
By deriving Eq. (2), we obtain:
0.8
0.7
0.6
0.5
0.4
0.3
0.2
0.1
0
dA
d[NH2Cl]
dt
d[P]
dt
λ
λ
λ
(3)
= εNH Cl
+ εP
.
2
dt
19
Taking into account the expressions for the reaction
rate, that gives:
dA
d[C5H10NNH2]
d[P]
dt
d[P]
dt
/
λ
λ
λ
19
1
(4)
.
= −εNH Cl
+
+ εP
(
)
2
dt
dt
As the ratio d[C5H10NNH2]/d[P] is equal to k1
Eq. (4) becomes:
k2, the
dA
k1
k2
d[P]
dt
d[P]
dt
λ
λ
⎛
⎜
⎝
⎞
⎟
⎠
λ
(5)
= −εNH Cl
1 +
+ εP
.
2
dt
220 240 260 280 300 320 340
, nm
The existence of an isosbestic point at λiso allows for
solution of the Eq. (6):
λ
Fig. 1. (a) Evolution of UV spectra during the interaction
dA
λiso
of piperidine with monochloramine. (b) Evolution of UV
(6)
= 0.
spectra in the first step of the reaction, time, min: 0 (
1), 0.93
dt
(
2
), spectra (3–19) were recorded successively in 0.47 min.
This leads to:
–2
–3
[C H NH] = 5
×
10 M, [NH Cl] = 2
×
10 M,
5
10
0
2
0
pH 12.89, 25°C.
⎛
k1 ⎞
λiso
λiso
= εP .
(7)
εNH Cl 1 +
⎜
⎟
2
k2
⎝
⎠
the evolution of NAPP concentration vs. time. Hence,
we obtain:
Hence, it is possible to follow the reaction kinetics by
recording the evolution of NH2Cl and NAPP instanꢀ
taneous concentrations. In fact, Eq. (1) for the disapꢀ
pearance rate of monochloramine can be rewritten as
follows:
[NH2Cl]
−
d[NH2Cl]
∫
[NH2Cl]0
(10)
α
β
[C5H10NNH2]
–d[NH2Cl]/d
t
= (k1
+ k2)[NH2Cl] [C5H10NH] , (8)
k1 + k2
=
d[C5H10NNH2].
where α and
β
are the partial orders of the reagents. In
∫
0
k1
the presence of PP excess and in the first moments of
From Eq. (10) we deduce:
[NH2Cl]0
the reaction, the slope
can be written as follows:
ψ = (k1 + k2)[C5H10NH]0.
ψ
of the curve
=
ln
k2
⎛
⎜
⎝
⎞
⎟
⎠
[NH2Cl]
[NH2Cl]0 – [NH2Cl] =
[C5H10NNH2]. (11)
1 +
f(t)
k1
As mentioned above, the study was carried out in
the diluted solution, following simultaneously
β
(9)
Simultaneously, the rate constant k1 was deterꢀ monochloramine concentration by UV spectrophoꢀ
mined from the experimental curve corresponding to tometry at = 243 nm and hydrazine concentration at
λ
KINETICS AND CATALYSIS Vol. 54
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652
DARWICH et al.
–ln[NH2Cl]
7.6
–ln
ψ
8.0
7.4
7.2
7.0
6.8
6.6
6.4
6.2
7.5
7.0
6.5
6.0
5.5
5.0
4.5
4.0
6.0
0
2.0
2.5
3.0
3.5
4.0
4.5
–ln[C5H10NH]0
5.0
2
4
6
8
10
, min
t
Fig. 2. Dependence of –ln[NH Cl] against time according
2
Fig. 3. Dependence of –ln
ψ
against –ln[C H NH]
5 10 0
–3
–3
to Eq. (8). [NH Cl] = 2
×
10 M, [C H NH] =
5 10 0
2
0
according to Eq. (9). [NH Cl] = 2
×
10 M, pH 12.89,
2
0
–2
5
×
10 M, pH 12.89, 25
°
C
.
25°C.
λ
= 237 nm after treatment with formaldehyde. Durꢀ iments, (k1
ing the first four minutes of the reaction, the curves
–ln[NH –ln[NH2Cl] = showed to be straight lines
with ꢀinterception equal to –ln[NH2Cl]0 and the and k2 at pH 12.89 (25
+
k2) and k1
equal to (61.0 1.2)
respectively. Hence, the corresponding values for k1
C) are 56
10–3 M–1 s–1 and
10–3 M–1 s–1, respectively.
/
×
k2 are practically constant and
10–3 M–1 s–1 and 11.2 0.4
,
f(t)
y
°
×
β
5
×
slope equal to
(k1
+
k2)
(Fig. 2). A deviaꢀ
[C5H10NH]0
tion was then observed increasing with reaction
progress. This phenomenon was accounted for by the
interference of the spectral bands of the products
responsible for the isosbestic point (Products P) as well
as of those stemming from NAPP oxidation [20].
Effect of pH. The influence of pH was studied
according to the same procedure using sodium
hydroxide solutions at concentrations ranging from
0.05 up to 1 M (T = 25°C). The corresponding values
of pH were calculated from [25, 26], which were carꢀ
ried out on the determination of activity coefficients of
The
β
value was determined at constant
monochloramine concentration equal to
2
1
×
10–3
10–2 up
M
and piperidine concentration varying from
×
10–2 M. The curve –ln
ψ
=
f
(–ln[C5H10NH]0) is
ꢀinterception equal to –ln(k1 k2
= 0.99 (Fig. 3).
[NH2Cl]0[C5H10NH]
lnꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀꢀ
[C5H10NH]0[NH2Cl]
to
a straight line of
and a slope equal to
9
×
y
+
)
β
3.5
3.0
2.5
2.0
1.5
1.0
0.5
Further experiments were carried out using HPLC
analysis by following monochloramine concentration
until the end of the first step. The value kapp
= k1 + k2
was evaluated for longer time, NAPP oxidation being
still neglected. Under these conditions, kapp was deterꢀ
mined from the Eq. (12) at [C5H10NH]0 ≠ [NH2Cl]0.
1
[C5H12NH]0 − [NH2Cl]0
[NH2Cl]0 [C5H12NH]
(12)
× ln
= f (t).
[C5H12NH]0 [NH2Cl]
Figure 4 represents the corresponding dependence for
a mixture of monochloramine and piperidine. The
overall results are listed in Table 1.
0
10
20
30
40
50
60
, min
t
The ratio k1
shows the plot of
(where [NH Cl] = [NH2Cl]0 – [NH2Cl]t), which is
a straight line2passing through the origin with a slope
equal to 1 + k2 k1. As follows from the results of experꢀ
/
k2 is determined from Eq. (11). Figure 5
[NH2Cl]0 [C5H10NH]
Δ
[NH2Cl] = ([C5H10NNH2])
f
ln
Fig. 4. Dependence of
against
[C5H10NH]0 [NH2Cl]
Δ
–3
time according to Eq. (12). [NH Cl] = 5
×
10 M,
2
0
[C H NH] = 0.02 M, pH 12.89, 25
°
C
.
/
5
10
0
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KINETIC AND MECHANISTIC STUDY OF
N
ꢀAMINOPIPERIDINE FORMATION
653
Table 1. Kinetic parameters for the reaction between monochloramine and piperidinee (pH 12.89, 25°C)
[NH2Cl]0
×
103 M [C5H10NH]0
,
×
103 M kapp
×
103 M–1 s–1* kapp
×
103 M–1 s–1**
,
k1/k2
,
,
1
20
20
20
20
20
10
30
40
50
90
30
15
10
59.6
62.4
60.0
61.4
59.0
61.7
63.3
61.1
62.4
61.0
–
–
–
–
59.5
61.4
–
–
–
–
–
–
11.5
11.2
–
11.3
10.9
–
10.8
–
–
2
3
5
6
2
2
2
2
2
5
6
6
60.2
59.6
61.6
–
11.8
–
61.3
–
* Samples analyzed by UV spectrophotometry.
** Samples analyzed by HPLC.
“–” means that the reaction was not followed by HPLC, only by UV or the other way round.
sodium hydroxide concentrated solutions. Table 2
shows that k1 increases with NaOH concentration,
while, under the same conditions, k2 appears to be
Mechanistic Aspect
As the reaction of NAPP formation showed to be
bimolecular with respect to each reagent (α ≈ β ≈ ),
1
constant at different alkalinity (
Temperature dependence. The effect of the temperꢀ
ature was studied at the temperature range 15–45
for monochloramine and piperidine concentrations
equal to
10–3 and 0.01 M, respectively. The variaꢀ
tion of kapp kapp k1 k2 with temperature follows the
Arrhenius law (Fig. 6), kapp 9.3
106 exp(–46.5/RT
M–1 s–1 (
app expressed in kJ/mol)
k2 = 5
×
10–3 M–1 s–1).
therefore this reaction presents a SN2 type mechanism:
NH2Cl + C5H10NH + OH–
→
(I)
(II)
C H NNH + Cl– + H O,
°C
→
2
5
10
2
C5H10NH + OH–
C5H10N– + H2O,
2
×
C H N– + NH Cl C H NNH + Cl–. (III)
→
(
=
+ )
5
10
2
5
10
2
=
×
)
At pH
≤
12.89, k1 is practically constant and
E
.
increases rapidly for higher pH values. A priori, the
[NH2Cl]
103, М
×
–lnkapp
Δ
4.0
1.0
0.9
0.8
0.7
0.6
0.5
0.4
0.3
0.2
0.1
3.5
3.0
2.5
2.0
1.5
1.0
0.0031
0.0032
0.0033
0.0034
0.0035
1/
, K–1
T
0
0.2
0.4
0.6 0.8
[C5H10NNH2]
1.0
103, М
×
Fig. 5. Dependence of
Δ
[NH Cl] against [C H NNH
]
5
10
2
2
Fig. 6. Temperature dependence of
k
for the reaction of
app
–3
according to Eq. (11). [NH Cl] = 3
×
10
M,
monochloramine with piperidine in Arrhenius coordinates.
2
0
–3
–3
[C H NH] = 0.02M, pH 12.89, 25
°C.
Δ
[NH Cl] =
[NH Cl]
=
2
×
10 M, [C H NH] = 10
×
10 M,
5
10
0
2
2
0
5
10
0
[NH Cl] – [NH Cl] .
t
pH 12.89.
2
0
2
KINETICS AND CATALYSIS Vol. 54
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654
DARWICH et al.
Table 2. Influence of pH on the reaction between monoꢀ
is a dimeric product, but it was not possible to suggest
its structure and the path of its formation.
chloramine and piperidine ([NH2Cl]0 = 2
×
10–3 M,
[C5H10NH]0 = 10
×
10–3 M, 25°C)
pH
O
[NaOH], M
k1
×
103, M–1 s–1
H O
2
oxidant
H2N–(CH2)4–C–H
0.05
0.10
0.30
0.50
0.80
1.00
12.69
12.89
13.33
13.53
13.74
13.83
55
56
64
72
79
84
N
H
N
1
H2N–(CH2)3–CH=CHOH
H O
2
PP
further
oxidation
N
O
N
H
OH
H
PP
2
pKa of PP
= 11.12) would explain proton transꢀ
(pKa
Scheme.
fer from piperidine followed by the nucleophilic attack
of C5H10N– ion on partially positive nitrogen of the
chlorinated derivative (reactions (II) and (III)).
However, the catalytic effect of OH– ions could be
the result of the partial dissociation of NH2Cl into
The proposed reaction scheme is in agreement with
the literature [29–32] indicating that the formation of
piperideine (
by different oxidants. Consequently, the product
responsible for the isosbestic point at = 277 nm
1) occurs via the oxidation of piperidine
(pKaNH Cl
2
chloramide NHCl–
= 18 [27, 28]), which
λ
reacts on PP according to equations (IV) and (V)
would correspond to a chromophore belonging to the
reaction scheme starting from piperidine and giving
) or an aminoaldehyde (see the aforeꢀ
mentioned scheme) via piperideine (
([NHCl–] increases at pH > 14):
piperidinone (
2
NH2Cl + OH–
NHCl– + H2O,
(IV)
1).
C5H10NH + NHCl– C H NNH + Cl–. (V)
→
5
10
2
In this paper, the exploitation of concentration–
time curves for Nꢀaminopiperidine formation via the
Raschig process combined with the existence of isosꢀ
bestic points in UV spectrophotometry shows the
presence of two competitive reactions: formation of
target hydrazine as a major product and piperideine as
a minor sideꢀproduct, which instantaneously underꢀ
goes a hydrolysis to give mainly an aminoaldehyde or
piperidinone. In all cases, the evolution of imine,
according to the two different ways described above,
does not affect the final yield of hydrazine (up to 93%)
[22]. The partial orders, the bimolecular rate constants
and the activation parameters were determined.
The interaction between NH2Cl and PP, being a
SN2 type reaction, belongs to a pseudoꢀalkaline catalꢀ
ysis, which might be linked with the dissociation of
NH2Cl into chloramide ions NHCl– (reaction (IV)).
Therefore, the reaction rate increases by about 50%
for a pH value ranging from 12.89 to 13.8.
Hence, at higher pH (pH > 12.89), the NAPP formaꢀ
tion would be the result of the two paths (III) and (V).
Consequently, it seems that there are two paths for the
NAPP formation: base independent and base cataꢀ
lyzed paths.
Reaction Products
The concurrent reaction was identified indirectly
by UV analysis, which reveals an isosbestic point, and
was kinetically quantified. Two techniques were used
to identify the different constituents appearing simulꢀ
taneously in the reaction: HPLC/MS and GC/MS.
Nevertheless, it was quite difficult to identify the prodꢀ
ucts of the parallel reaction because of its weak contriꢀ
bution to the overall reaction (~10%).
GC/MS analysis indicated the presence of four
products 1–4 with molecular weights equal to
83, 99, 154 and 165, respectively. The study of fragꢀ
mentation allowed to determine that and correꢀ
spond to piperideine ( = 83) and piperidinone
= 99).
m/z =
1
2
m/z
REFERENCES
(m/z
1. Int. Patent WO 03027076, 2003.
2. US Patent 5663366 1997.
3. Schmidt, E.W., Hydrazine and Its Derivatives: Preparaꢀ
tion, Properties, Application, New York: Wiley, 2001.
4. GDR Patent 76520 1970.
N
H
O
N
5. Ohme, R. and Preuschhof, H., J. Prakt. Chem., 1970,
Piperideine (
1
)
Piperidinone (2)
vol. 312, p. 349.
Product
3 could not be identified and probably
6. Murakami, Y., Yokoyama, Y., Sasakura, C., and Tamaꢀ
comes from stationary phase of the column. Product
4
gawa, M., Chem. Pharm. Bull., 1983, vol. 31, p. 423.
KINETICS AND CATALYSIS Vol. 54
No. 6
2013

KINETIC AND MECHANISTIC STUDY OF
N
ꢀAMINOPIPERIDINE FORMATION
655
7. Hanna, C. and Schueler, F.W., J. Am. Chem. Soc., 1952, 21. Darwich, C., Elkhatib, M., Steinhauser, G., and
vol. 74, p. 3693.
Delalu, H., Helv. Chim. Acta, 2009, vol. 92, p. 98.
22. Darwich, C., Ph.D. Thesis, Lyon: Claude Bernard
8. Wright, J.B. and Willette, R.E., J. Med. Pharm. Chem.
,
Univ. Lyon I, 2005.
1962, vol. 5, p. 819.
23. Elkhatib, M., Peyrot, L., Scharff, J.P., and Delalu, H.,
Int. J. Chem. Kinet., 1998, vol. 30, p. 129.
24. Elkhatib, M., Marchand, A., Counioux, J.J., and
Delalu, H., Int. J. Chem. Kinet., 1995, vol. 27, p. 757.
25. Akerlof, G. and Kegeles, G., J. Am. Chem. Soc., 1939,
vol. 61, p. 1027.
26. Akerlof, G. and Kegeles, G., J. Am. Chem. Soc., 1940,
9. French Patent 1400256, 1965.
10. Smith, P.A.S. and Pars, H.G., J. Org. Chem., 1959,
vol. 24, p. 325.
11. Lunn, G., Sansone, E.B., and Keefer, L.K., J. Org.
Chem., 1984, vol. 49, p. 3470.
12. Podgornaya, I.V., Tayusheva, N.N., and Postovskii, I.Y.,
Zh. Obshch. Khim., 1964, vol. 34, p. 2521.
vol. 62, p. 620.
13. Netherlands Patent 6510107.
14. Belgian Patent 812749, 1974.
15. US Patent 3317607 1967.
16. US Patent 2979505 1961.
17. US Patent 3154538 1964.
27. Delalu, H., Marchand, A., Ferriol, M., and Cohenꢀ
Adad, R., J. Chim. Phys. Phys.ꢀChim. Biol., 1981,
vol. 78, p. 247.
28. French Patent 8701334, 1987.
29. Anbar, M. and Yagil, G., J. Am. Chem. Soc., 1962,
vol. 84, p. 1790.
18. Labarthe, E., Bougrine, A.J., Pasquet, V., and
Delalu, H., Kinet. Catal, 2012, vol. 53, p. 25.
30. Lenoble, W.J., Tetrahedron Lett., 1966, vol. 7, p. 727.
19. DuricheꢀColas, C., Ph.D. Thesis, Lyon: Claude Berꢀ
31. Mitteilung, J. and Hausler, J., Monatsh. Chem., 1987,
nard Univ. Lyon I, 2001.
vol. 118, p. 865.
20. Darwich, C., Elkhatib, M., Steinhauser, G., and 32. Mohrle, H. and Mayer, S., Tetrahedron Lett., 1968,
Delalu, H., Kinet. Catal, 2009, vol. 50, p. 103. vol. 7, p. 889.
KINETICS AND CATALYSIS Vol. 54
No. 6
2013