Synthesis of N-aminopyrrolidine by the raschig process: Kinetic and mechanistic study of the monochloramine-pyrrolidine interaction

Article abstract of DOI:10.1002/kin.20833

1-Pyrrolidinamine (NAPY) belongs to a family of large compounds, namely the alkylhydrazines, used as precursors for different targets in fine chemicals, such as pharmaceuticals and cosmetics. Different synthetic methods are described in the literature; however, many of them are not adaptable on a large scale. The Raschig process appears to be the most relevant method for preparing hydrazines at the industrial scale: hydrazines are obtained by two successive reactions. The first involves the formation of monochloramine from sodium hypochlorite and excess ammonia. The second consists of reacting, in a basic medium, the monochloramine previously synthesized with excess amine to provide the corresponding hydrazine. It is a clean and selective method, distinguished by its nonpolluting aspect, its low cost, and the feasibility of continuous transposition to industrial scale. However, it presents some disadvantages linked to the low hydrazine concentrations in the synthesis solutions. The optimization of the synthesis parameters is therefore essential and requires a detailed kinetic and mechanistic study of the reaction of NAPY formation by the chloramine/pyrrolidine interaction. The kinetics of the NAPY formation reaction were studied in alkaline medium, at first at a temperature of 25°C. Excess pyrrolidine was used with respect to NH₂Cl, in order to minimize the influence of side reactions. Owing to the high reaction rates, the essays were carried out in a dilute medium, using reagent concentrations ranging between 1 × 10^-3 and 4 × 10^-2 M. The ionic strength of the medium was established by NaOH concentration (0.1 M). Then, the influence of the temperature was studied between 15 and 45°C for NH₂Cl and PY concentrations, respectively, equal to 2 × 10^-3 and 0.01 M, in order to check the conformance to the Arrhenius law. Finally, the characterization of the reaction mixture permitted establishment of a global reaction scheme, including two main secondary reactions.

Full text of DOI:10.1002/kin.20833

Synthesis of
N-Aminopyrrolidine by the
Raschig Process: Kinetic
and Mechanistic Study of
the Monochloramine-
Pyrrolidine Interaction
A. DHENAIN, C. DARWICH, M. R. FRANGIEH, L. GOUTAL, H. DELALU
UCBL/CNRS/CNES/Herakles (Groupe Safran), Universit e´ Claude Bernard Lyon 1, F-69622 Villeurbanne Cedex, France
Received 31 May 2013; revised 7 October 2013; accepted 12 October 2013
DOI 10.1002/kin.20833
Published online 25 April 2014 in Wiley Online Library (wileyonlinelibrary.com).
ABSTRACT: 1-Pyrrolidinamine (NAPY) belongs to a family of large compounds, namely the alkyl-
hydrazines, used as precursors for different targets in fine chemicals, such as pharmaceuti-
cals and cosmetics. Different synthetic methods are described in the literature; however, many
of them are not adaptable on a large scale. The Raschig process appears to be the most relevant
method for preparing hydrazines at the industrial scale: hydrazines are obtained by two succes-
sive reactions. The first involves the formation of monochloramine from sodium hypochlorite
and excess ammonia. The second consists of reacting, in a basic medium, the monochloramine
previously synthesized with excess amine to provide the corresponding hydrazine. It is a clean
and selective method, distinguished by its nonpolluting aspect, its low cost, and the feasibil-
ity of continuous transposition to industrial scale. However, it presents some disadvantages
linked to the low hydrazine concentrations in the synthesis solutions. The optimization of the
synthesis parameters is therefore essential and requires a detailed kinetic and mechanistic
study of the reaction of NAPY formation by the chloramine/pyrrolidine interaction. The kinetics
of the NAPY formation reaction were studied in alkaline medium, at first at a temperature of
◦
2
5 C. Excess pyrrolidine was used with respect to NH2Cl, in order to minimize the influence
of side reactions. Owing to the high reaction rates, the essays were carried out in a dilute
−
3
−2
medium, using reagent concentrations ranging between 1 × 10 and 4 × 10 M. The ionic
strength of the medium was established by NaOH concentration (0.1 M). Then, the influence
◦
of the temperature was studied between 15 and 45 C for NH2Cl and PY concentrations, re-
spectively, equal to 2 × 10− and 0.01 M, in order to check the conformance to the Arrhenius
3
Correspondence to: A. Dhenain; e-mail: anne.dhenain@
univ-lyon1.fr.
2014 Wiley Periodicals, Inc.
ꢀ
C

SYNTHESIS OF N-AMINOPYRROLIDINE BY THE RASCHIG PROCESS
339
law. Finally, the characterization of the reaction mixture permitted establishment of a global
reaction scheme, including two main secondary reactions. ꢀC 2014 Wiley Periodicals, Inc. Int J
Chem Kinet 46: 338–349, 2014
INTRODUCTION
This green and selective method is distinguished
by its nonpolluting aspect (chemistry in water with-
out using any organic solvent), its low cost (inexpen-
sive reagents NH3 and NaOCl) and the feasibility of
a continuous transposition to an industrial scale. Nev-
ertheless, it presents some disadvantages linked to the
low hydrazine concentrations in the synthesis solu-
tions, due to the dilution of the initial reactants and to
the existence of a large number of secondary interac-
tions that require nonstoichiometric conditions at all
stages of the synthesis.
Despite its disadvantages, the Raschig process re-
mains the most relevant method for an industrial
process development. The optimization of the synthe-
sis parameters requires a detailed kinetic and mech-
anistic study of the reaction of NAPY formation by
chloramine–pyrrolidine interaction.
1-Pyrrolidinamine also named n-aminopyrrolidine
(NAPY) belongs to a family of large compounds,
namely the alkylhydrazines, used as precursors for dif-
ferent targets in fine chemicals, such as pharmaceuti-
cals [1] and cosmetics.
In particular, it is used as a reducing agent, an an-
tioxidant, and as an epoxy hardener. It also acts as
an intermediate in the synthesis of tetrahydropyrazi-
dine and its derivatives, like hexahydropyridazine, tra-
ditionally used as raw materials in pharmaceutical and
agrochemicals (herbicides) [2,3]. It is also used as an
intermediate in the synthesis of cosmetic products and
compounds such as pigments and dyes [4] that have
applications in industrial chemistry.
Different synthetic methods are described in the lit-
erature; however, many of them are not adaptable on
a large scale due to various drawbacks. Indeed, some
of them are based on the use of nitrosamines, which
present a great toxicity due to their carcinogenic effect
EXPERIMENTAL
Reagents
[5]; others are based on the use of costly reagents, such
as hydrazine hydrate or chlorohydrate [2,6]. Hence,
another alternative consists in obtaining NAPY from
the corresponding secondary amine, but the yields of
hydrazine observed are very low [7]. Other synthe-
sis’ assays were performed by the gaseous chloramine
process, leading to good yields; however, problems of
ammonium chloride precipitation were encountered,
resulting in the blockage of the chloride inlet [8].
However, the Raschig process is a general method
for preparing hydrazines including two successive
steps and presenting many advantages. The prepara-
tion of NAPY via this method has been largely studied
in our laboratory [9,10]. The first step of the synthe-
sis involves the formation of monochloramine from
sodium hypochloride and an excess of ammonia. The
second one consists of reacting the monochloramine
previously synthesized with an excess of amine, in
an alkaline medium, to provide the corresponding
hydrazine [11,12]:
Pyrrolidine (99% + purity) was provided by Acros
Organics, and ammonia in solution (32%) was pro-
vided by Prolabo. Sodium hypochlorite solutions were
obtained by dilution of concentrated solutions (48–53
chlorometric degrees) supplied by ARKEMA. They
◦
were kept at 5 C and systematically analyzed before
use.
All other reagents and salts used in this study
(NaOH, Na2HPO4, KH2PO4, KI, Na2S2O3, CH2O
(36%), and CH3COOH) were supplied by Sigma
Aldrich or Acros. Water was demineralized by
circulation on an ion-exchange resin (conductivity
−
1
<5 μS cm ).
Monochloramine solutions are not stable and need
to be prepared in situ. Monochloramine solutions (1 M)
were prepared in quasistoichiometric conditions, using
+
-
+
-
NH3
R1
+
Na OCl
NH Cl
+
Na OH
2
R1
NaOH
N-NH2
+
NaCl
+
H O
2
N-H
+
NH Cl
2
R2
R2
International Journal of Chemical Kinetics DOI 10.1002/kin.20833

3
40
DHENAIN ET AL.
a process developed in our laboratory [13]. It consists
of adding a sodium hypochlorite solution containing
Iodometry. A Metrohm 848 Titrino Plus titrator with
automatic equivalence point recognition was used. The
method is based on the redox reactions between iodide
and hypochlorite ions (titration of NaOCl) or NH2Cl
(titration of monochloramine solutions) in the presence
of acetic acid. The iodine formed is then titrated with
0.1 M sodium thiosulfate solution.
0
.12 molar equivalent of NaOH with respect to NaOCl
◦
(
50 mL, 2.3 M NaOCl, 0.28 M NaOH, T = −15 C)
to an ammonium chloride solution (2.53 M, 50 mL,
◦
T = −11 C). This method is advantageous compared
with the classical preparation of NH2Cl using nonstoi-
chiometric conditions ([NH4Cl] + [NH3])/[NaOCl] =
3
[14] because it allows us to obtain concentrated
UV Spectrophotometry. The samples were analyzed
with a CARY 100 double-beam VARIAN UV–visible
spectrophotometer, linked to a data-acquisition system.
Quartz cells of 5–10 mm pathway were used. The con-
centration of monochloramine was directly monitored
monochloramine solutions with very low amounts of
ammonia.
Monochloramine so obtained is then extracted in
diethyl ether and washed with aliquots of water. This
extraction allows us to obtain monochloramine solu-
tions free of sodium hydroxide and sodium chloride.
Then monchloramine aqueous solutions can be pre-
pared, in situ, by reextraction from the ethereal phase.
A further stripping step eliminates from the aqueous
solutions the residual solvent and ammonia traces. At
this stage of preparation, the NH2Cl concentration is
about 0.3 M, and monochloramine solutions are right
−1
by making use of its UV absorption (εNH Cl = 458 M
2
−1
cm at λ = 243 nm). However, n-aminpyrrolidine,
which does not directly absorb in UV, was monitored
after derivation with formaldehyde (50-fold excess in
a solution of pH 6.88), to convert NAPY into its chro-
mophore corresponding hydrazone FNAPY (εFNAPY =
−1
−1
5
046 M cm at λ = 240 nm) [15].
−3
away prepared by dilution of 1 or 2 × 10 M concen-
trations.
GC–MS. GC–MS analyses were performed to char-
acterize the synthesis solutions and to particularly
identify NAPY and the by-products of the reaction.
Therefore, an Agilent Technologies 6890 chromato-
graph coupled to a 5970 mass spectrometer was
used, equipped with a quadruple analyzer, where the
molecules are ionized by electronic impact (70 eV).
The ionic fragments were identified according to
their mass/charge (m/z) ratio. The chromatograph was
equipped with a HP Innowax capillary column (30 m ×
0.32 mm (i.d.), film thickness = 0.25 μm). The tem-
Apparatus and Experimental Protocol
The apparatus used is composed of a thermostated re-
actor of 250 mL capacity, fitted with a placed tempera-
ture sensor and a magnetic stirrer. Several inlets in the
upper part of the reactor allowed reactants to be added,
aliquots to be taken, and temperature to be measured.
The reactor was maintained at a constant temperature
by using a Julabo cooling thermostat.
◦
◦
Pyrrolidine (PY) solutions (100 mL) were in-
troduced into the reactor, whereas monochloramine
perature program was set from 40 C up to 260 C, with
a heating rate of 30 C/min.
◦
(
NH2Cl) solutions were prepared in volumetric flasks
and placed in the bath of the cooling thermostat. When
temperature of the two reactants is homogeneous, the
NH2Cl solution is introduced quickly into the reactor
RESULTS AND DISCUSSION
(
at time t0) and samples are taken from the reaction
Kinetic Study of the NAPY Formation by
Reaction of Monochloramine on Pyrrolidine
medium and analyzed during the course of the reac-
tion.
The kinetics of NAPY formation reaction was studied
in alkaline medium at pH 12.89 ([NaOH] = 0.1 M), at
Analyses
◦
first at a temperature of 25 C. Excess PY was used with
Different analytical techniques were used to determine
the concentrations of the reactants and products along
the reaction.
Sodium hypochlorite and monochloramine so-
lutions were titrated by iodometry. NH2Cl and
NAPY concentrations were followed by UV (ul-
traviolet) spectrometry, and the reaction products
were identified by GC–MS (gas chromatography–mass
spectrometry).
respect to NH2Cl, to minimize the influence of side
reactions. Owing to the high reaction rates, the essays
were carried out in a dilute medium, using reagent
concentrations ranging from 1 × 10 to 4 × 10 M.
The ionic strength of the medium was established by
NaOH concentration (0.1 M). Under these conditions,
the kinetic parameters of the reaction between NH2Cl
and PY were determined via UV spectrophotometry,
by monitoring NH2Cl and NAPY concentrations.
−3
−2
International Journal of Chemical Kinetics DOI 10.1002/kin.20833

SYNTHESIS OF N-AMINOPYRROLIDINE BY THE RASCHIG PROCESS
341
Figure 1 UV-absorption spectra recorded over time of a chloramine–pyrrolidine reaction mixture of chloramine and pyrrolidine
[C4H8NH]0 = 10 × 10− M, [NH2Cl]0 = 2 × 10 M, [NaOH] = 0.1 M, T = 25 C). t0 indicates initial time, and tf indicates
3
−3
◦
(
final time.
Figure 1 represents a UV recording of the reaction
mixture at different times. The reaction was conducted
centrations of NH2Cl and NAPY with UV spectropho-
tometry, which permits a precise determination of the
rate laws. They have been determined by means of a
method based on exploiting the isobestic point as well
as the concentration–time curves. The measurements
were approximately limited at the reactions half-lives.
Under these conditions, chloramine and pyrrolidine
disappear to give rise not only to NAPY but also to
compound P. Indeed, the rate of chloramine disappear-
ance, involved in reactions (1) and (2), can be written
as follows:
−3
with initial concentrations of 2 × 10 M for NH2Cl
−3
and 10 × 10 M for PY. A decrease in the UV charac-
teristic band of chloramine at λ = 243 nm and a gradual
deviation of the absorption maximum toward higher
wavelengths are observed. Moreover, the presence of
an isosbestic point at λ = 277 nm can be noticed.
The presence of this isobestic point testifies a de-
fined stoichiometry between two chromogenic com-
pounds, a reactant that is chloramine and its instan-
taneous product. It excludes any slow subsequent
reaction involving one of the two compounds. This
characteristic point can only be interpreted by the ex-
istence of a parallel, so-called twin, a reaction that
involves the same reactants of NAPY formation reac-
tion and leading to a chromogenic compound that we
will name P:
d[NH2Cl]
d[NAPY] d [P]
−
=
+
(1)
dt
dt
dt
The absorbance of the reaction mixture at any wave-
length λ can be written as follows (l = 1.00 cm):
k1
+
+
+
HCl
NH Cl
NH
NH
N-NH2
+
(1)
(2)
2
k2
NH Cl
P
2
Σi Pi
Rate Laws
λ
λ
P
It is possible to kinetically characterize the synthesis
by following the evolution of the instantaneous con-
Dλ = ε
[NH Cl] + ε [P]
NH2Cl
2
International Journal of Chemical Kinetics DOI 10.1002/kin.20833

3
42
DHENAIN ET AL.
After differentiating the above equation, one obtains
reaction. This deviation is especially related to the in-
terference of the spectral absorption band responsi-
ble for the isosbestic point and to the oxidation of
the so-obtained NAPY. Therefore the monitoring of
chloramine concentration with respect to time was
carried out for a series of different initial reactants
concentrations.
dDλ
d[NH2Cl]
dt
d[P]
dt
λ
λ
=
ε
+ εP
NH2Cl
dt
Taking into account relation (1), this leads to
ꢀ
ꢁ
The value of β was then determined with a con-
dDλ
d[P] d[NAPY]
d[P]
dt
−3
λ
λ
stant chloramine concentration of 2 × 10 M while
=
−ε
+
+ εP
NH2Cl
−
3
dt
dt
dt
pyrrolidine’s concentration ranged from 10 × 10 up
−3
to 45 × 10 M. The plot ln ψ = f (ln [C4H8NH]0)
gives a straight line with a slope β = 1.0017 and a y in-
tercept ln (k1 + k2) (Fig. 3). Hence, the above results
confirm that the partial orders of the reaction com-
pared with chloramine and pyrrolidine are respectively
equal to 1.
(
2)
As the ratio d[NAPY]/d[P] is equal to k1/k2, relation
(
2) becomes
ꢀ
ꢁ
dDλ
=
d[P]
dt
k1
k2
d[P]
dt
λ
λ
−ε
1 +
+ εP
NH2Cl
dt
Rate of NAPY Formation. The rate of NAPY forma-
tion can be expressed by relation (4), where k1, α, and
β represent, respectively, the rate constant of NAPY
formation and the partial orders with respect to chlo-
ramine and amine:
Moreover, the presence of an isobestic point at λiso
is due to the relation
dDλiso
dt
=
0
d[NAPY]
dt
α
β
v1 =
= k1[NH2Cl] [PY]
(4)
From this reasoning, one can deduce that reactions
1) and (2) are linked by their rate through constants.
(
Denoting the initial concentrations of chloramine
and pyrrolidine, respectively, by [NH2Cl]0 and [PY]0,
relation (1) leads to Eq. (5) and then to relation (6) after
integration and supposing that α = β = 1:
Rate of NH2Cl Disappearance. The rate of NH2Cl
disappearance can be expressed by relation (3), where
k1, k2, α, and β, respectively, represent the rate con-
stants of NAPY and P formation and the partial orders
with respect to chloramine and pyrrolidine:
[NAPY]
ꢂ
d[NAPY]
(
[NH2Cl]0 − [NAPY])([PY]0 − [NAPY])
0
α
β
−
d [NH Cl]/dt = (k + k2) [NH Cl] [C H8NH]
2
1
2
4
t
ꢂ
(3)
=
k1dt
(5)
0
The rate of NH2Cl disappearance was studied
1
and the value of k1 +k2 thereby calculated, for a
series of mixtures of different compositions. The
rate laws were established via the Ostwald isolation
method.
[
PY]0 − [NH2Cl]0
ꢀ
ꢁ
[NH2Cl]0([PY]0 − [NAPY])
·
ln
= k1 · t (6)
[PY]0([NH2Cl]0 − [NAPY])
The initial concentrations of chloramine were lim-
−
3
−3
ited to 1 × 10 M or 2 × 10 M to remain in the linear
range of the spectrophotometer for the measurement of
UV absorbance, whereas concentrations of pyrrolidine
ranged from 5 × 10 to 45 × 10 M (pH 12.89,
The rate constant k1 was therefore determined from
the experimental curves representing the evolution
of the NAPY’s concentration as a function of time
(relation (6)). As mentioned previously, the NAPY con-
centration can be followed by UV spectroscopy after
derivation with formaldehyde.
−3
−3
◦
T = 25 C).
In the presence of amine excess and in the first in-
stants of the reaction, the plot –ln [NH2Cl] = f(t) is
Figure 4 represents an example of UV absorption
recording, over time, of the reaction mixture chlo-
ramine/pyrrolidine after derivation with formaldehyde.
The reaction was conducted for initial concentrations
a straight line with a slope equal to ψ = (k1 + k2)
β
0
[
(
C4H8NH] and a y intercept equal to –ln [NH2Cl]0
Fig. 2). Then, one can observe from the straight line
−3
−3
a deviation that increases with the progression of the
of 2 × 10 M in chloramine and 10 × 10 M in
International Journal of Chemical Kinetics DOI 10.1002/kin.20833

SYNTHESIS OF N-AMINOPYRROLIDINE BY THE RASCHIG PROCESS
343
Figure 2 NH2Cl–C4H8NH interaction: Determination of rate constants sum k1 + k2, ([NH2Cl]0 = 1 × 10− M, [C4H8NH]0 =
3
−3
◦
5
× 10 M, pH 12.89, T = 25 C).
Figure 3 NH2Cl–C4H8NH interaction: Determination of the partial order with respect to the pyrrolidine ([NH2Cl]0 =
−3
◦
2
× 10 M, pH 12.89, T = 25 C).
pyrrolidine. Aliquots taken from the reaction mixture
at different times were divided into two categories. The
first one treated with a 50-fold excess of formaldehyde-
in a phosphate buffer solution and poured into sam-
ple UV cells, and the second was diluted with buffer
solution following the same procedure as for sample
aliquots, then, poured into the reference UV cell. It
is important to notice that the presence of the re-
action mixture in the reference cell is necessary be-
cause it contents interfering substances influencing
the spectra.
We can notice that in these conditions that the
NAPY yield does not exceed 75%, which confirms,
on one hand, the existence of a twin reaction responsi-
ble for the consumption of a part of chloramine, and,
on the other hand, the partial degradation of the nascent
NAPY by oxidation with chloramine. The oxidation of
NAPY by chloramine being negligible until reaction
half-lives, k1 was determined from relation (6).
1
The
· ln([
plots
representing
) = f (t), ([PY] ꢁ= [NH Cl] )
[
PY]0−[NH2Cl]0
[
NH2Cl]0([PY]0−[NAPY])
0
2
0
PY]0([NH2Cl]0−[NAPY])
are in all cases straight lines going through the origin,
with same slope equals to k , which additionally
1
proves that partial orders are equal to 1 with respect
to each reactant. Figure 5 shows initial chloramine
−
3
and pyrrolidine concentrations of 2 × 10 and 10 ×
−3
◦
10 M, respectively (T = 25 C, pH 12.89). The plot
linearity is demonstrated up to t ≤ 60 min, which
corresponds to a conversion rate of advancement
of ε = ([NH Cl] – NH Cl])/[NH Cl] = 0.65.
2
0
2
2
0
In addition, the observed deviation is related to
the oxidation of the nascent NAPY by chloramine
International Journal of Chemical Kinetics DOI 10.1002/kin.20833

3
44
DHENAIN ET AL.
Figure 4 UV absorption recording over time of a reaction mixture of chloramine and pyrrolidine after derivation with
−3
−3
◦
formaldehyde ([C4H8NH]0 = 10 × 10 M, [NH2Cl]0 = 2 × 10 M, [NaOH] = 0.1 M, T = 25 C). t0 indicates initial time, and
tf indicates final time.
Figure 5 NH2Cl–C4H8NH interaction: Determination of the rate constant k1 ([NH2Cl]0 = 2 × 10− M, [C4H8NH]0 =
3
−3
◦
2
0 × 10 M, T = 25 C, pH 12.89).
mentioned above, which becomes more important at
the end of the reaction.
verify the invariability of k1. The uncertainty of mea-
surement is about 10% for k1 and 6% for k1 + k2. The
overall results are presented in Table I.
For the segment of time studied herein, the straight
line obtained passes through the origin with an exper-
The sum (k1 + k2) is nearly constant and equal
−
1
−1
−3
−3
−3
−1 −1
M s . On the other
M s . Hence, the
imental slope equal to 2.3881 M min and a corre-
to 45 × 10 ± 2.3 × 10
2
−1 −1
lation coefficient R = 0.996. The yield of the reaction
hand, k1 = 40 ± 1.7 × 10
then defined with respect to NH2Cl (φ = [NAPY]∞/
corresponding values of k1 and k2 at pH 12.89 and
◦
[
NH2Cl]0) is close to 72%.
T = 25 C are
Several assays were carried out for a series of re-
action mixtures of different reactant compositions, to
k1 = 40 × 10−
3
M
−1 −1
s
,
k2 = 5 × 10−3
M
−1 −1
s
International Journal of Chemical Kinetics DOI 10.1002/kin.20833

SYNTHESIS OF N-AMINOPYRROLIDINE BY THE RASCHIG PROCESS
345
◦
Table I Determination of the Rate Constants of the Reaction between Chloramine and Pyrrolidine (T = 25 C,
pH 12.89)
a
b
[
(
NH2Cl]0
M)
[C4H8NH]0
(M)
k1
(k1 + k2)
ψ
−
1
−1
−1 −1
−1
(M
s
)
(M
s
)
(min )
−
−
−
−
−
−
−
−
3
3
3
3
3
3
3
3
−3
−3
−3
−3
−3
−3
−3
−3
−3
−3
2
2
2
2
1
2
2
2
× 10
× 10
× 10
× 10
× 10
× 10
× 10
× 10
10 × 10
39.7 × 10
41.0 × 10
38.3 × 10
39.6 × 10
37.0 × 10
40.2 × 10
44.5 × 10
48.8 × 10
45.6 × 10
–
0.0268
0.0320
0.0630
–
0.0160
0.0455
0.0952
0.1202
−3
10 × 10
−3
20 × 10
−3
20 × 10
−3
−3
−3
−3
−3
5 × 10
44.6 × 10
45.1 × 10
46.8 × 10
46.0 × 10
−3
15 × 10
−3
30 × 10
41.6 × 10-3
−3
−3
40 × 10
40.7 × 10
a
Standard uncertainty is 0.1.
Standard uncertainty is 0.06.
b
Influence of Temperature. The influence of the tem-
Influence of pH. Although the systematic study of
the influence of pH on the reaction rate has not been
carried out in this study, similar studies on formation
reactions of other hydrazines through the Raschig way
are described in the literature.
◦
◦
perature has been studied between 15 C and 45 C, for
NH2Cl and PY concentrations, respectively, equal to
−3
2
× 10 and 0.01 M. The variation of k1 as a func-
tion of the temperature conforms to the Arrhenius law
Fig. 6).
Table II presents the influence of temperature on the
(
For example, the formation of n-aminoaza-3-
bicyclo-[3,3,0]octane by a reaction of monochloramine
on aza-3-bicyclo-[3,3,0]octane has been studied in de-
constants k1 and k1 + k2 in the same conditions. We can
◦
notice that the evolution of k1/k2 seems to indicate an
tail [16]. The reaction constant was calculated at 25 C,
◦
optimum for the temperature of the medium at 35 C:
with initial monochloramine and amine concentra-
−
3
−3
M
in the first time, the increase of temperature leads to
tions, respectively, equal to 2 × 10 , 30 × 10
◦
−3
−3
an increase of k1 but above 35 C, k2 increases more
or 1 × 10 , and 15 × 10 M, and NaOH concentra-
−
1
than k1, which shows that higher temperatures favor
tions in the range between 0.01 and 3.00 mol L . The
−3
−1 −1
s
the parallel reactions.
reaction constant is equal to 38.9 × 10 L mol
Ea
1
−
According to the Arrhenius law, k1 = A1.e R.T , the
plot –ln k1 = f(1/T) gives a straight line with a slope
E1/R and a y intercept –ln A1. Ea1 and A1, respectively,
correspond to the activation energy and the Arrhenius
at pH <12.5 and increases rapidly at more basic pH
−1
−1
at pH 14.42.
values, to reach 90.3 L mol
Another similar study was carried out on the
n-aminopiperidine formation reaction, from
s
−1
monochloramine and piperidine, for NaOH con-
centrations between 0.05 and 1 M. The authors noticed
factor of the global reaction (Ea1 in kJ mol ):
−
57.25
R.T
8
that the reaction constant k increases from 55 ×
1
k1 = 4.88 × 10 × e
−3
−3
−1 −1
1
0
to 84 × 10 L mol
s
when pH increases
−
1 −1
−1
×
(k in M
s
, Ea1 in kJ mol
)
−3
M,
1
from 12.69 to 13.83 ([NH Cl] = 2 × 10
2
0
−
3
◦
[
C5H10NH]0 = 10 × 10 M, T = 25 C) [17]. The
from which the enthalpy and the entropy can be
deduced:
hydrazine formed only differs from NAPY with one
carbon, which let us suppose that similar results would
be observed for the NAPY formation in the same
pH range.
ꢀ
ꢁ
A1.h
ekB .T
◦
0#
ꢀ
H 10 # = Ea1 − RT ,ꢀS1 = R ln
By analogy with the observed results for the for-
mation of similar hydrazines, we can assume that an
increase in the medium’s alkalinity leads to the in-
crease in the reaction rate, which demonstrates that the
where kB and h represent the Boltzmann constant and
Planck universal constant, respectively (kB = 1.380 ×
−
23
−34
J s). The quantities have
10
J/K, h = 6.623 × 10
−
reaction of formation of NAPY is catalyzed by OH
the following numerical values:
Mechanistic Aspect
ꢀ
H 10 # = 54.8 kJ/mol,
ꢀS 10 # = −86.9 J/mol · k
The NAPY formation mechanism is of the SN2 type.
The limiting step corresponds to a nucleophilic at-
tack of the electron doublet of the amine nitrogen,
The uncertainty is about 10% for these thermody-
namic values.
International Journal of Chemical Kinetics DOI 10.1002/kin.20833

3
46
DHENAIN ET AL.
−3
Figure 6 Influence of temperature on the reaction between monochloramine and pyrrolidine ([NH2Cl]0 = 2 × 10 M,
C4H10NH]0 = 10 × 10− M, pH 12.89).
3
[
Table II Influence of the Temperature on the Reaction between Monochloramine and Pyrrolidine ([NaOH] = 0.1 M,
◦
T = 25 C)
k1a
M
(k1 + k2)
b
T
[NH2Cl]
(10 M)
[C4H8NH]
(10 M)
[NaOH]
(M)
◦
−3
−3
−3
−1 −1
−3
−3 −3
(
C)
(10
s
)
(10
M
s
)
k1/k2
1
2
3
4
5
2
2
2
2
10
10
10
10
0.1
0.1
0.1
0.1
15.5
40.0
99.0
20.0
45.1
104.4
238.0
4.5
5.1
5.4
5
5
5
184.5
53.5
a
b
Standard uncertainty is 0.1
Standard uncertainty is 0.06
on the weakly electropositive site of the nitrogen
of the chlorinated derivative. Proton elimination is
instantaneous:
_
+
N
H
+
+
N
H
H N Cl
Cl
N NH2
H Cl
2
d+ d−
NH2
The rate of the NAPY formation, controlled by the
limiting step, is bimolecular and thus agrees with the
kinetic results. Its value is linked to the nucleophilicity
of the amine, its degrees of substitution, and its elec-
tronic environment. Indeed, similar k1 values have been
−
+
NH2Cl ꢀ NHCl + H
−
−
C4H8NH + NHCl → C4H8NNH2 + Cl
calculated for other disubstituted cyclic hydrazines
◦
[
4
M
2,17] at pH 13 and T = 25 C: kf (C7H12NNH2) =
Characterization of the Reaction Medium
−3
−1 −1
−3
5.45 × 10
M
s
, kf (C5H10NNH2) = 56 × 10
A GC–MS analysis of the reaction medium was carried
out to identify the main chemical species present in the
medium at the end of synthesis and to consider the
reaction mechanisms that can lead to each species.
Figure 7 presents the characterization of the end
products by GC–MS, in a reaction mixture contain-
ing about 5 wt% of NAPY, obtained in concen-
trated conditions from a 1 M monochloramine solution
−1
−1
s ).
−
The catalytic effect of the OH ions can be ex-
plained by considering the partial dissociation of
NH2Cl into chloramide ion NHCl (pKaNH2Cl = 18
−
[
18,19]):
NH2Cl + C4H8NH → C4H8NNH2 + HCl
International Journal of Chemical Kinetics DOI 10.1002/kin.20833

SYNTHESIS OF N-AMINOPYRROLIDINE BY THE RASCHIG PROCESS
347
Figure 7 Chromatogram and corresponding mass spectra of a final reaction mixture obtained by reaction of monochloramine
0.1 mol, 1 M) and pyrrolidine (0.8 mol, 99%).
(
(
0
100 mL, 0.1 mol) and pure pyrrolidine (67 mL,
.8 mol). The chromatogram includes five peaks, ob-
previously named P and responsible for the isobestic
point observed by UV spectroscopy (Fig. 1), is formed
by the twin reaction NH2Cl + PY.
served at tr = 1.9, 2.2, 2.8, 3.6, and 5.0 min. Each peak
was identified from the major peak fragments of its
mass spectrum, compared with the reference spectra.
The ion identification results are presented in Table III.
The results show, on one hand, that pyrrolidine is
partially oxidized by chloramine, which leads to the
formation of 3,4-dihydro-2H-pyrrole. This product,
On the other hand, the presence of 1,2-
diazacyclohex-1-ene is observed, which results from
the reaction of oxidation of NAPY by chloramine.
Indeed, by analogy with the phenomena observed in
our laboratory in the case of unsymmetrical dimethyl-
hydrazine, n-aminoaza-3-bicyclo-[3,3,0]octane and
International Journal of Chemical Kinetics DOI 10.1002/kin.20833

3
48
DHENAIN ET AL.
Table III Identification of the Mass Spectra
Peak
Tr (min)
Ion fragment (relative abundance)
Identification
1
2
3
4
5
1.9
2.2
2.8
3.6
5.0
29 (43), 31 (100), 32 (75)
42 (23), 43 (100), 70 (76), 71 (53)
41 (100), 43 (79), 68 (54), 69 (69), 70 (59)
42 (45), 43 (23), 58 (29), 68 (19), 85 (100), 86 (81)
84 (100), 83 (59), 69 (15), 55 (28), 56 (28), 42 (19), 41 (17)
Methanol
Pyrrolidine
3,4-Dihydro-2H-pyrrole
NAPY
1,2-Diazacyclohex-1-ene
−
n-aminopiperidine, the oxidation of NAPY by chlo-
ramine leads to the formation of a diazene (aminoni-
trene), which rearrange itself by dynamic isomerism
to give a hydrazone with a molecular weight of
catalyzed by OH ions. Finally, we conclude that this
is an SN -type mechanism reaction.
2
The characterization of the reaction mixture permit-
ted to underline the presence of two main by-products
of the reaction: 3,4-dihydro-2H-pyrrole and 1,2-
diazacyclohex-1-ene, and therefore to a global reac-
tion scheme, including two main secondary reactions.
On one hand, pyrrolidine is partially oxidized by chlo-
ramine, which leads to the formation of a chromophore
−1
8
4 g · mol . This reaction, limited by the use of
an excess of amine, is however observed in a small
proportion.
The observed results enable us to conclude the fol-
lowing reaction scheme:
k1
+
+
NH Cl
NH
NH
N-NH2
HCl
(1)
2
k2
k3
+
NH Cl
+
NH Cl
(2)
(3)
N
2
4
+
NH Cl
N
N
+
NH Cl
4
NH +
2
2
N
N
+
(
4)
N
N
N
H
OH-
CONCLUSIONS
product, observed by UV spectroscopy. On the other
hand, as soon as NAPY is formed, it is partially oxi-
dized by chloramine to give an aminonitrene that rear-
ranges itself into a hydrazone.
Further work on the detailed kinetic study of these
secondary reactions would enable us to determine all
the reaction constants involved in the global reaction
scheme, to establish a global kinetic model, and to
define the optimal (pH, excess of amine) conditions
for the formation of NAPY by the Raschig process.
This work has focused on the kinetic study of the for-
mation reaction of NAPY from chloramine and pyrro-
lidine. The results permitted to conclude that the reac-
tion has a global order equal to two, one with respect
to each reactant. The reaction constant k1 is equal to
−3
−1 −1
40 × 10
M s . The variation of k1 as a function
of the temperature was studied and revealed to con-
form to the Arrhenius law. Moreover, by analogy with
other hydrazines, we can assume that the reaction is
International Journal of Chemical Kinetics DOI 10.1002/kin.20833

SYNTHESIS OF N-AMINOPYRROLIDINE BY THE RASCHIG PROCESS
349
BIBLIOGRAPHY
9. Duriche-Colas, C. Ph.D. Thesis no. 213-2001, Lyon 1
University, France, 2001.
1
. Vevert, J. P.; Gasc, J. C.; Delevallee, F.; Petit, F. FR
Patent from Eur. Pat. Appl. (1988), EP 280627 A2
10. El Khatib, M. Ph.D. Thesis no. 89-94, Lyon 1 University,
France, 1994.
1
9880831.
11. Raschig, F. Ber Dts, Chem Ges 1907, 40, 4580–
4588.
2
. Hasegawa, Y.; Hyoda, S.; Fujita, H.; Sawada, H.; Oki,
Y. JP Patent from Eur. Pat. Appl. (1998), EP 850930 A2
12. Raschig, F. Chem.-Ztg. 1907, 31, 926.
13. Delalu, H.; Duriche, C.; Berthet, J.; Le, G. P. FR Patent
from Eur. Pat. Appl. (2004), EP 1415953 A1 20040506.
14. Delalu, H. Ph.D. Thesis no. 77-29, Lyon 1 University,
France, 1977.
15. Frangieh, M. R. Ph.D. Thesis no. 16-2011, Lyon 1 Uni-
versity, France, 2011.
16. Delalu, H.; Marchand, A. J Chim Phys Phys-Chim Biol
1992, 89(6), 1413–1425.
17. Darwich, C. Ph.D. Thesis no. 29-2005, Lyon 1 Univer-
sity, France, 2005.
18. Cohen, R. A.; Cohen, A.; Delalu, H.; Marchand, A.;
Mauge, R. ZA8704526A, 1988.
19. Delalu, H.; Marchand, A.; Ferriol, M.; Cohenadad, R. J
Chim Phys Phys-Chim Biol 1981, 78(3), 247–252.
19980701.
3
. Satow, J. F. K.; Itoh, K.; Ikai, T.; Suzuki, K.; Nawamaki,
T.; Watanabe, S. US Patent 5 039 331, 1991.
. De Lachararriere, O.; Breton, L.; Loussouarn, G. FR
Patent from Eur. Pat. Appl. (1997), EP 764435 A1
4
1
9970326.
. Lunn, G.; Sansone, E. B.; Keefer, L. K. J Org Chem
984, 49(19), 3470–3473.
5
6
1
. Maekawa, T.; Tomotaki, Y.; Ishikawa, K.; Nabeshima,
A.; Furuichi, T. JP Patent from Eur. Pat. Appl. (1999),
EP 894788 A1 19990203.
. Kantor, M. L. US4564677, 1986.
. Jain, S. R.; Chellappa, D. Proc Indian Academy of
Sciences–Chemical Sciences 1985, 95(4), 381–389.
7
8
International Journal of Chemical Kinetics DOI 10.1002/kin.20833