Mechanism of elimination of amino acid derivatives in the gas phase. Pyrolysis kinetics of ethyl picolinate, ethyl 1-methylpipecolinate and picolinic acid

Article abstract of DOI:10.1002/poc.568

The kinetics of the gas-phase elimination of the title compounds were determined in a static reaction system over the temperature range 180.8-419.4 °C and the pressure range 15-86 Torr (1 Torr = 133.3 Pa). The reactions are homogeneous and unimolecular and obey a first-order rate law. The observed rate coefficients are represented by the following Arrhenius equations: for ethyl picolinate, log[k₁(s^-1)] = (11.30 ± 0.24) -(180.9 ± 3.0) Kj mol^-1 (2.303 RT)^-1, for ethyl 1-methylpipecolinate, log[k₁(s^-1)] = (13.36 ± 0.31) -(209.5 ± 3.9) Kj mol^-1 (2.303 RT)^-1 and for picolinic acid, log[k₁(s^-1)] = (12.05 ± 0.10) -(135.7 ± 0.9) Kj mol^-1 (2.303 RT)^-1. The data from this work together with those reported in the literature confirm previous considerations that amino acids or α-nitrogen substituents of carboxylic acids undergo an extremely rapid decarboxylation process. The pyrolysis kinetics of picolinic acid, which is an intermediate of ethyl picolinate elimination, showed a dramatic fast decomposition into pyridine and CO₂ gas. The decarboxylation process of α-amino or α-nitrogen substituents of carboxylic acids differs from the decarboxylation elimination of several known α-substituted carboxylic acids in the gas phase. Copyright

Full text of DOI:10.1002/poc.568

JOURNAL OF PHYSICAL ORGANIC CHEMISTRY
J. Phys. Org. Chem. 2003; 16: 84–88
Published online in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1002/poc.568
Mechanism of elimination of amino acid derivatives in the
gas phase. Pyrolysis kinetics of ethyl picolinate, ethyl 1-
methylpipecolinate and picolinic acid
1
1
2
2
2
Jennifer Lafont, Adolfo Ensuncho, Rosa M. Dom õÂ nguez, Alexandra Rotinov, Armando Herize,
3
2
Jairo Quijano and Gabriel Chuchani *
1
Departamento de Qu õÂ mica, Universidad de Cordoba, Monter õÂ a, Colombia
Centro de Qu õÂ mica, Instituto Venezolano de Investigaciones Cient Âõ ®cas (IVIC), Apartado 21827, Caracas 1020-A, Venezuela
Departamento de Qu õÂ mica, Universidad Nacional de Colombia, Sede Medell õÂ n, Medell õÂ n, Colombia.
2
3
Received 22 February 2002; revised 12 August 2002; accepted 13 August 2002
ABSTRACT: The kinetics of the gas-phase elimination of the title compounds were determined in a static reaction
system over the temperature range 180.8–419.4°C and the pressure range 15–86 Torr (1 Torr = 133.3 Pa). The
reactions are homogeneous and unimolecular and obey a first-order rate law. The observed rate coefficients are
À1
represented by the following Arrhenius equations: for ethyl picolinate, log[k (s )] = (11.30 Æ 0.24) À(180.9 Æ
1
À1
À1
À1
À1
3
(
.0) kJ mol (2.303 RT) , for ethyl 1-methylpipecolinate, log[k (s )] = (13.36 Æ 0.31) À(209.5 Æ 3.9) kJ mol
À1 À1 À1 À1
1
2.303 RT) and for picolinic acid, log[k (s )] = (12.05 Æ 0.10) À(135.7 Æ 0.9) kJ mol (2.303 RT) . The data
1
from this work together with those reported in the literature confirm previous considerations that amino acids or a-
nitrogen substituents of carboxylic acids undergo an extremely rapid decarboxylation process. The pyrolysis kinetics
of picolinic acid, which is an intermediate of ethyl picolinate elimination, showed a dramatic fast decomposition into
pyridine and CO gas. The decarboxylation process of a-amino or a-nitrogen substituents of carboxylic acids differs
2
from the decarbonylation elimination of several known a-substituted carboxylic acids in the gas phase. Copyright 
2
002 John Wiley & Sons, Ltd.
KEYWORDS: gas-phase pyrolysis; kinetics; mechanism; amino acid derivatives; ethyl picolinate; ethyl 1-
methylpipecolinate; picolinic acid
INTRODUCTION
It is very difficult to displace an amino or a nitrogen
derivative as a leaving substituent L in organic
compounds in gas-phase elimination reactions. In addi-
tion, most simple amino acids are solids, which limits
their suitability for their investigation as neutral mol-
Experimental determinations and ab initio theoretical
calculations on the gas-phase pyrolyses of 2-substituted
1–7
carboxylic acids suggested a decarbonylation process
as described in reaction (1). The acidic H of the COOH
group assists the leaving group L for elimination,
followed by the participation of the oxygen of the
carbonyl to give an unstable a-lactone. This intermediate
rapidly decomposes into the corresponding carbonyl
compound and CO gas.
8
ecules in the gas phase. However, in recent work it was
possible to examine the formation of neutral amino acid
intermediates from the pyrolyses of their corresponding
ethyl ester derivatives. The mechanism of these reactions
was formulated as in reaction (2).
According to the results of the above-mentioned
8
work, neutral amino acids are very reactive species in
the gas phase. This is because the N atom becomes more
polarized when approaching the acidic H of the COOH
group, thus causing a lowering of the energy. Therefore, a
very rapid decomposition is to be expected. The nitrogen
atom as a 2-substituent of carboxylic acids is not a
leaving group, and decarboxylation [reaction (2)] rather
than decarbonylation [reaction (1)] was obtained. The
mechanistic rationalization for the fast decomposition of
neutral amino acid intermediates is supported from the
elimination kinetics of N,N-dimethylglycine, an inter-
mediate of N,N-dimethylglycine ethyl ester pyrolysis.
The former substrate was found to be decomposed ꢁ96
ꢀ
1†
*
Correspondence to: G. Chuchani, Centro de Qu ´ı mica, Instituto
Venezolano de Investigaciones Cient ı´ ficas (IVIC), Apartado 21827,
Caracas 1020-A, Venezuela.
E-mail: chuchani@quimica.ivic.ve
Contract/grant sponsor: Fondo Nacional de Ciencia, Tecnologia e
Innovaci o´ n (FONACIT); Contract/grant number: S1-97000005.
Copyright  2002 John Wiley & Sons, Ltd.
J. Phys. Org. Chem. 2003; 16: 84–88

KINETICS OF GAS-PHASE ELIMINATION OF AMINO ACIDS
85
ꢀ2†
8
times faster than the latter at 400°C. This means that
N,N-dimethylglycine decomposes rapidly at the working
temperature of the corresponding ethyl ester. Conse-
quently, the gas-phase elimination of neutral amino acids
is expected to occur at very low temperatures. To further
our knowledge of the mechanistic pathway of the gas-
phase elimination of a-amino or a-nitrogen substituents
of carboxylic acids, this work was initiated to examine
the gas-phase pyrolysis kinetics of ethyl picolinate and
ethyl 1-methylpipecolinate. In addition to these sub-
strates, picolinic acid, which may be an intermediate in
ethyl picolinate elimination, was examined in order to
determine the extent of decomposition of a-nitrogen
substituents of carboxylic acids.
no significant variation in the rate coefficients was
obtained in these experiments when using both clean
Pyrex and seasoned Pyrex vessels with a surface to
volume ratio of 6.0 relative to both clean Pyrex and
seasoned Pyrex normal vessels. The effect of different
proportions of toluene inhibitor is shown in Table 4.
Therefore, this elimination reaction is molecular and not
free radical in nature. No induction period was observed.
The rate coefficients are reproducible with a standard
deviation of not greater than 5% at a given temperature.
ꢀ3†
RESULTS ANDDISCUSSION
Ethyl picolinate
The elimination reaction of ethyl picolinate [reaction (3)]
The first-order rate coefficients for ethyl picolinate,
demands P /P = 3.0, where P and P are the final and
initial pressures, respectively. The average experimental
calculated from k = (2.303/t)log[2P /(3P À P )] were
f
0
f
0
1
0
0
t
found to be independent of the initial pressure (Table 5).
The rate coefficient, at a given temperature, is measured
at each reaction time, and after a significant number of
lectures obtained, the average k value is estimated within
Æ5% standard deviation. A plot of log(3P À P ) vs time t
P /P value at four different temperatures and 10 half-
f
0
lives is 2.9 (Table 1). Additional confirmation of the
stoichiometry, up to 75% decomposition, was obtained
by comparing the pressure measurements with the
quantitative analyses of ethylene formation (Table 2).
Elimination reaction (3) is homogeneous (Table 3), since
0
t
gave a good straight line up to 75% decomposition. The
variation of the rate coefficients with temperature and the
Table 1. Rate of ®nal (P ) to initial pressure (P ) of the substrate
f
0
a
a
Substrate
Temperature (°C)
P0 (Torr)
Pf (Torr)
Pf/P0
Average
2.95
Ethyl picolinate
380.3
391.2
399.9
414.1
381.1
389.6
401.1
419.4
190.8
199.7
210.2
220.3
26
30.5
29
57
65
71.5
64.5
45
26.5
30
74
90
88
172
197
210
184
132
49.5
56
2.84
2.95
3.00
3.00
3.00
2.93
2.85
2.93
1.87
1.87
1.83
7.85
Ethyl 1-methylpipecolinate
Picolinic acid
2.93
1.86
37.5
40.5
68.5
75
a
1
Torr = 133.3 Pa.
Copyright  2002 John Wiley & Sons, Ltd.
J. Phys. Org. Chem. 2003; 16: 84–88

8
6
J. LAFONT ET AL.
Table 2. Stoichiometry of the reaction
Substrate
Temperature (°C)
Parameter
Value
Ethyl picolinate
370.0
379.0
199.7
Time (min)
6
12
21
39
59
Reaction (%) (pressure)
Ethylene (%) (GC)
Time (min)
13.26
13.56
7
25.30
25.25
14
42.60
43.35
23
58.94
58.87
37
76.15
76.76
65
Ethyl 1-methylpipecolinate
Picolinic acid
Reaction (%) (pressure)
Ethylene (%) (GC)
Time (min)
15.65
15.59
4
30.60
30.00
7
51.40
48.75
10
63.46
61.65
13
81.10
82.32
16
Reaction (%) (pressure)
Pyridine (%) (GC)
24.2
24.4
38.0
40.1
49.6
47.7
59.6
58.7
68.3
65.9
Table 3. Homogeneity of pyrolysis reactions
À1 a
4
À1 b
4
À1 c
Compound
S/V (cm
)
10 k (s
)
10 k (s
)
1
1
Ethyl picolinate at 399.9°C
1
6
1
6
1
6
19.90
19.76
12.48
12.47
11.42
12.35
19.90
19.91
12.43
12.45
11.58
11.70
Ethyl 1-methylpipecolinate at 401.1°C
Picolinic acid at 199.7°C
a
S = surface area; V = volume.
Clean Pyrex vessel.
Vessel seasoned with allyl bromide.
b
c
a
Table 4. Effect of free radical inhibitor on rates
b
c
4
À1
Substrate
Temperature (°C)
Ps (Torr)
P (Torr)
Pi/Ps
10 k (s
)
i
1
Ethyl picolinate
380.3
3
4
5
6
2
3
6
6
7
5
4
3
4
3
3
1
–
18
40
88
76
128
–
34
75
88
90
–
–
6.82
6.81
0
0.5
0.8
1.5
2.9
3.4
–
2
6.70
0
6.83
6
6.80
8
6.73
Ethyl 1-methylpipecolinate
Picolinic acid
401.1
199.7
8
12.74
12.71
12.49
12.93
12.70
11.28
11.42
11.17
11.58
4.5
0
0.5
1.1
1.5
2.1
–
1.5
2.4
3.0
8
3
2
4
66
81.5
107
3.5
0
a
Cyclohexene or toluene inhibitor.
b
P
s
= pressure of the substrate.
c
P
i
= pressure of the inhibitor.
Table 5. Variation of the rate coef®cients with initial pressure
Substrate
Temperature (°C)
Parameter
Value
Ethyl picolinate
391.2
P (Torr)
15
11.57
45
36.78
17
23.89
25
11.71
66
36.62
29
24.51
31
11.57
80
36.70
36
24.36
62
11.55
86
36.86
45
24.21
0
4
À1
1
0 k (s
)
)
)
1
Ethyl 1-methylpipecolinate
Picolinic acid
419.4
210.2
P (Torr)
0
4
À1
1
0 k (s
1
P (Torr)
0
4
À1
1
0 k (s
1
Copyright  2002 John Wiley & Sons, Ltd.
J. Phys. Org. Chem. 2003; 16: 84–88

KINETICS OF GAS-PHASE ELIMINATION OF AMINO ACIDS
Table 6. Temperature dependence of the rate coef®cients
87
Substrate
Parameter
Value
Ethyl picolinate
Temperature (°C)
349.7
1.35
359.6
2.30
370.7
4.00
380.3
6.81
391.2
11.59
399.9
19.88
414.1
4
À1
1
0 k (s
)
33.84
1
À1
À1
À1
Rate equation: log[k (s )] = (11.30 Æ 0.24) À(180.9 Æ 3.0)kJ mol (2.303 RT) ; r = 0.9993
1
Ethyl 1-methylpipecolinate
Temperature (°C)
364.6
1.51
371.4
2.57
381.1
4.38
389.6
7.46
401.1
12.71
409.4
21.60
419.4
36.70
4
À1
1
0 k (s )
1
À1
À1
À1
Rate equation: log[k (s )] = (13.36 Æ 0.31) À(209.5 Æ 3.9)kJ mol (2.303 RT) ; r = 0.9991
1
Picolinic acid
Temperature (°C)
180.8
2.75
190.9
5.93
199.7
210.2
24.40
220.3
48.69
4
À1
1
0 k (s
)
11.58
1
À1
À1
À1
Rate equation: log[k (s )] = (12.05 Æ 0.10) À(135.7 Æ 0.9)kJ mol (2.303 RT) ; r = 0.9998
1
corresponding Arrhenius equation is given in Table 6
90% confidence limits from a least-squares procedure).
shown in Table 6, where 90% confidence limits from a
least-squares procedure are given.
(
Ethyl 1-methylpipecolinate
Picolinic acid
The molecular elimination of this substrate, described in
The experimental stoichiometry for the pyrolysis of this
reaction (4), requires that P /P = 3.0. The average
substrate, as shown in reaction (5), requires P /P = 2.0.
f
0
f
0
experimental P /P values at four different temperatures
The average experimental P /P value obtained at four
f
0
f 0
and 10 half lives is 2.93 (Table 1). The stoichiometry of
reaction (4), up to 80% decomposition, was satisfactorily
verified by comparing the percentage decomposition of
the substrate from pressure measurements with that
obtained from the gas chromatographic (GC) measure-
ment of the product ethylene (Table 2).
different temperatures and 10 half-lives was 1.86 (Table
1). It was possible to corroborate the stochiometry of
reaction (5), up to 65% decomposition, by comparing the
percentage decomposition of the substrate from pressure
measurements with those obtained by GC analysis of the
product pyridine (Table 2). The effect of the surface area
in the rate of elimination was determined carried by
employing a vessel with a surface to volume ratio six
times greater than that of the normal vessel. The rate
coefficient for formation of pyridine was unaffected in
the clean Pyrex vessel and in the seasoned glass packed
and unpacked vessels. The clean packed Pyrex vessel
showed a very small heterogeneous effect (Table 3).
Cyclohexene inhibitor had no effect on the rates (Table 4)
and no induction period was observed. The rates are
reproducible with a relative standard deviation of not
greater than 5% at a given temperature.
ꢀ4†
The reaction can be said to be homogeneous since no
significant effects on the rates were obtained on using
both clean Pyrex and seasoned Pyrex vessels with a
surface to volume ratio of 6.0 relative to the normal clean
and seasoned Pyrex vessels in these experiments (Table
ꢀ5†
3
). The presence of different proportions of toluene, an
The rate coefficient of this substrate was calculated
effective free radical inhibitor, had no effect on the rates
and no induction period was obtained (Table 4). The rates
are reproducible with a standard deviation not greater
than 5% at a given temperature.
from k = (2.303/t) log P /(2P À P ) and was found to be
1
0
0
t
independent of the initial pressure (Table 5). A plot of
log(2P À P ) aganist time t gave a good straight line for
0
t
up to 65% reaction. The temperature dependence of the
rate coefficients and the corresponding Arrhenius equa-
tion are given in Table 6 (90% confidence limits from a
least-squares procedure).
The rate coefficients for elimination, calculated from
k = (2.303/t)log[2P /(3P À P )], are invariable to initial
1
0
0
t
pressures (Table 5), and the first-order plots of
log(3P À P ) against time t gave a good straight line
The k value of ethyl picolinate shows that it undergoes
elimination slightly faster than ethyl 1-methylpipecoli-
nate (Table 7). This small but significant difference in
rate coefficients may be attributed to the aromaticity of
0
t
for up to 80% decomposition. The temperature depen-
dence of the rate coefficients is shown in Table 6. The
experimental data were fitted to the Arrhenius equation as
Copyright  2002 John Wiley & Sons, Ltd.
J. Phys. Org. Chem. 2003; 16: 84–88

8
8
J. LAFONT ET AL.
Table 7. Kinetic parameters for pyrolysis reactions at 360°C
4
À1
À1
≠
À1 À1
≠
À1
≠
À1
Compound
k  10 (s
)
Ea (kJ/mol) Log[A (s )] DS (J mol
K
)
DH (kJ mol
)
DG (kJ mol)
1
Ethyl picolinate
Ethyl 1-methylpipecolinate
Picolinic acid
2.36
1.18
71161
180.9 Æ 3.0 11.30 Æ 0.24
209.5 Æ 3.9 13.36 Æ 0.31
135.7 Æ 0.9 12.05 Æ 0.10
À43.1
À3.7
À28.8
175.6
204.2
130.4
182.1
204.8
134.8
9
,10
the pyridine group. The delocalized p-system of pyridine
must exert a greater electron-withdrawing effect than the
piperidine ring. The reaction mechanism of these
substrates may be explained as in reaction (2).
The homogeneous, unimolecular elimination of pico-
linic acid, which is produced as an intermediate in
reaction (3), gives, as expected, an extremely rapid
decomposition that is 2500 times faster than that for ethyl
picolinate pyrolysis at 360°C (Table 7). Consequently,
neutral amino acid types of molecules must undergo a
very rapid decomposition and at very low temperatures.
The mechanism of picolinic acid elimination is depicted
in reaction (6).
in a static reaction system as described previously
with an Omega DP41-TC/DP41-RTD high-performance
digital temperature indicator. The rate coefficients were
determined from the pressure increase. The temperature
was controlled by a Shinko DC-PS resistance thermo-
meter controller and an Omega Model SSR280A45 solid-
state relay, maintained within Æ0.2°C and measured with
a calibrated platinum–platinum–13% rhodium thermo-
couple. No temperature gradient was observed along the
reaction vessel. The picolinic acid substrate was
dissolved in acetic acid and injected directly into the
reaction vessel with a syringe through a silicone rubber
septum. The amount of substrate used for each reaction
was ꢁ0.01–0.1 ml.
ꢀ6†
Acknowledgement
The financial support of FONACIT (Fondo Nacional de
Ciencia, Tecnolog ı´ a e Innovaci o´ n) of Venezuela through
Project No. S1-97000005 is highly appreciated.
EXPERIMENTAL
Ethyl picolinate (Aldrich) and ethyl 1-methylpipecolinate
Aldrich) of >99.0% purity (GC: Porapak Q, 80–100
(
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J. Phys. Org. Chem. 2003; 16: 84–88