The mechanism of neutral amino acid decomposition in the gas phase. The elimination kinetics of N,N-dimethylglycine ethyl ester, ethyl 1-piperidineacetate, and N,N-dimethylglycine

Article abstract of DOI:10.1002/kin.1043

The gas-phase elimination kinetics of the ethyl ester of two α-amino acid type of molecules have been determined over the temperature range of 360-430°C and pressure range of 26-86 Torr. The reactions, in a static reaction system, are homogeneous and unimolecular and obey a first-order rate law. The rate coefficients are given by the following equations. For N,N-dimethylglycine ethyl ester: log k₁(s^-1) = (13.01 ± 3.70) - (202.3 ± 0.3)kJ mol^-1 (2.303 RT)^-1 For ethyl 1-piperidineacetate: log k₁(s^-1) = (12.91 ± 0.31) - (204.4 ± 0.1)kJ mol^-1 (2.303 RT)^-1 The decompositon of these esters leads to the formation of the corresponding α-amino acid type of compound and ethylene. However, the amino acid intermediate, under the condition of the experiments, undergoes an extremely rapid decarboxylation process. Attempts to pyrolyze pure N,N-dimethylglycine, which is the intermediate of d imethylglycine ethyl ester pyrolysis, was possible at only two temperatures, 300 and 310°C. The products are trimethylamine and CO₂. Assuming log A = 13.0 for a five-centered cyclic transition-state type of mechanism in gas-phase reactions, it gives the following expression: log k₁(s^-1) = (13.0) - (176.6)kJ mol^-1 (2.303 RT)^-1. The mechanism of these α-amino acids differs from the decarbonylation elimination of 2-substituted halo, hydroxy, alkoxy, phenoxy, and acetoxy carboxylic acids in the gas phase.

Full text of DOI:10.1002/kin.1043

The Mechanism of Neutral
Amino Acid Decomposition
in the Gas Phase. The
Elimination Kinetics of N,N-
Dimethylglycine Ethyl Ester,
Ethyl 1-Piperidineacetate,
and N,N-Dimethylglycine
ADOLFO ENSUNCHO,1 M. JENNIFER LAFONT,1 ALEXANDRA ROTINOV,2
2
2
3
´
ROSA M. DOMINGUEZ, ARMANDO HERIZE, JAIRO QUIJANO,
GABRIEL CHUCHANI2
1Departamento de Quı´mica, Universidad de Cordoba, Monter´ıa, Colombia
2Centro de Qu´ımica, Instituto Venezolano de Investigaciones Cient´ıficas (I.V.I.C.), Caracas, Venezuela
3Departamento de Quı´mica, Universidad Nacional de Colombia, Sede Medellı´n, Medell´ın, Colombia
Received 26 September 2000; accepted 13 April 2001
ABSTRACT: The gas-phase elimination kinetics of the ethyl ester of two ␣-amino acid type of
molecules have been determined over the temperature range of 360–430ЊC and pressure range
of 26–86 Torr. The reactions, in a static reaction system, are homogeneous and unimolecular
and obey a first-order rate law. The rate coefficients are given by the following equations. For
N,N-dimethylglycine ethyl ester:
log k1(sϪ1) ϭ (13.01 Ϯ 3.70) Ϫ (202.3 Ϯ 0.3)kJ molϪ (2.303 RT)Ϫ
For ethyl 1-piperidineacetate:
log k1(sϪ1) ϭ (12.91 Ϯ 0.31) Ϫ (204.4 Ϯ 0.1)kJ molϪ (2.303 RT)Ϫ
1
1
1
1
The decompositon of these esters leads to the formation of the corresponding ␣-amino acid
type of compound and ethylene. However, the amino acid intermediate, under the condition
of the experiments, undergoes an extremely rapid decarboxylation process. Attempts to py-
rolyze pure N,N-dimethylglycine, which is the intermediate of dimethylglycine ethyl ester py-
rolysis, was possible at only two temperatures, 300 and 310ЊC. The products are trimethyl-
amine and CO2. Assuming log A ϭ 13.0 for a five-centered cyclic transition-state type of
mechanism in gas-phase reactions, it gives the following expression: log k1(sϪ1) ϭ (13.0) Ϫ
1
(176.6)kJ molϪ (2.303 RT)Ϫ1. The mechanism of these ␣-amino acids differs from the decar-
bonylation elimination of 2-substituted halo, hydroxy, alkoxy, phenoxy, and acetoxy carboxylic
acids in the gas phase. ᭧ 2001 John Wiley & Sons, Inc. Int J Chem Kinet 33:465–471, 2001
Correspondence to: G. Chuchani (chuchani@quimica.ivic.ve)
᭧ 2001 John Wiley & Sons, Inc.

466
ENSUNCHO ET AL.
INTRODUCTION
siderations according to the nature of the substrate un-
der examination.
Recent works in both experimental determinations and
ab initio theoretical calculations on the gas phase pyr-
olyses of 2-substituted chloro, hydroxy, alkoxy, phen-
oxy, and acetoxy carboxylic acids [1–7] suggested a
mechanism in which the acidic H of the COOH group
assists the leaving group for elimination. This is fol-
lowed by the participation of the oxygen carbonyl to
give the unstable ␣-lactone [reaction (1)]. The ␣-lac-
An interesting theoretical study [13] of the zwitter-
ϩ
ionic form of glycine (NH3 CH2COO)Ϫ) using the ab
initio molecular orbital technique, at the Hartree-Fock
level, reached the conclusion that glycine zwitterion
does not exist in the gas phase.
In view of the scarce information on gas-phase py-
rolysis of amino acids at subatmospheric pressure, in-
cluding the above theoretical consideration, the
O
O
O
dϩ
9C9C
9C9C
C9C
ϩ HL
O
dϪ
OH
L
O
L
H
L ϭ Cl, OH, OR, OPh, OAc
C"O ϩ CO
(1)
present work aimed at examining the elimination ki-
netics of some type of amino acids in the gas phase.
Unfortunately, most simple amino acids are solids that
on heating sinter or decompose into amorphous ma-
terials. Moreover, they are insoluble in most organic
solvents. Their high solubility in water, forming zwit-
terion species, limits their study as neutral molecules
in the gas phase. However, it is possible to study the
formation of neutral amino acids intermediate from
pyrolysis of their corresponding derivatives, such as
the ethyl esters. In this manner, some information
about their mode of mechanistic decomposition as
neutral molecules may be obtained. Consequently, the
study of gas-phase elimination kinetics of N,N-dime-
thylglycine ethyl ester, ethyl 1-piperidineacetate, and
N,N-dimethylglycine has been undertaken.
tone rapidly decomposes into the corresponding car-
bonyl compound and carbon monoxide.
An interesting substituent at the 2-position of carbox-
ylic acids is the amino group, as in the known amino
acid molecules. However, the amino or a nitrogen de-
rivative, as a leaving group in organic molecules, has
been found to be very difficult for displacement in gas-
phase elimination reactions. Because of this, the gas-
phase pyrolysis of some types of amino acids may
probably undergo a different mechanistic process from
that described in reaction (1).
The literature reports the pyrolysis of amino acids
[8–9] and their sodium salts [10] as a potential method
for identification of their constituents in peptides and
proteins. However, the analytical technique of gas
chromatography and mass spectra either were inade-
quate to detect all the products or because different
decomposition processes occurred in related amino
acid substrates. An additional reference is the thermal
decomposition of aromatic and heteroaromatic amino
acids [11] carried out in stainless steel reactors, be-
tween 400–600ЊC from 4 s to 1 min, with complex
results.
EXPERIMENTAL
N,N-dimethylglycine (97%), N,N-dimethylglycine
ethyl ester (98%), and ethyl 1-piperidine acetate (98%)
were acquired from Aldrich. The quantitative chro-
matographic analysis of the product ethylene was de-
termined in a column of Porapak Q 80-100 mesh. The
verifications of the substrates and identifications of
Ratcliff et al. [12] have pyrolyzed several structur-
ally different amino acids in a stainless steel tube at-
tached directly to a gas chromatograph at 500ЊC. The
results of this method led to various mechanistic con-

THE MECHANISM OF NEUTRAL AMINO ACID DECOMPOSITION IN THE GAS PHASE
467
products were carried out by GLC/MS (Saturn 2000,
Varian). Capillary column DB Ϫ5MS, 30 m ϫ 0.250
mm, i.d. 0.25 ␮m.
The stoichiometry described by reaction (2) requires
Pf ϭ 3Po, where Pf and Po are the final and the initial
pressures, respectively. The average experimental re-
sults of Pf /Po values at four different temperatures and
10 half-lives was 3.23 (Table I). Verification of stoi-
chiometry (2), up to 65% decomposition, was obtained
by comparing the pressure measurements with the
quantitative gas chromatographic analysis of ethylene
formation (Table II). The pyrolysis reaction (2) is ho-
mogeneous (Table III), since no significant variation
on the rates 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 the
normal vessel. The effect of different proportions of
the free radical inhibitor on the elimination process is
given in Table IV). Therefore, the reaction is molec-
ular in nature. No induction period was detected and
the rates were reproducible with a relative standard
deviation not greater than 5% at a given temperature.
The first-order rate coefficients of this substrate,
calculated from k1 ϭ (2.303/t) log[2Po/(3Po Ϫ Pt)]
were found to be invariable of the initial pressure (Ta-
ble V), and a plot of log(3Po Ϫ Pt) against time t was
satisfactorily linear up to about 65% reaction. The
temperature dependence of the rate coefficient is given
in Table VI. The results given in Table VI lead, by
using the least-squares method and 90% confidence
coefficient, to the Arrhenius equation shown.
The kinetic experiments were performed in a static
reaction system as described [14–15] with some mod-
ifications and additions of modern electronic and elec-
trical devices. The rate coefficients were determined
manometrically. The temperature was controlled by a
resistance thermometer controller, Shinko DC-PS
25RT, and an Omega solid-state relay, Model SSR280
AC45, maintained within Ϯ0.2ЊC and measured with
a calibrated platinum–platinum 13% rhodium ther-
mocouple. No temperature gradient along the reaction
vessel was observed. The ethyl ester substrates, and
N,N-dimethylglycine, dissolved between 20 and 30%
in acetic acid, were injected directly into the reaction
vessel with a syringe through a silicone rubber septum.
The amount of the substrates employed for each de-
composition process was approximately 0.01–0.1 ml.
RESULTS AND DISCUSSION
N,N-Dimethylglycine Ethyl Ester
The products of the gas-phase pyrolysis of N,N-di-
methylglycine ethyl ester, in a static system, are pre-
dominantly trimethylamine, ethylene, and carbon di-
oxide [reaction (2)].
(CH3)2NCH2COOCH2CH3 !: (CH3)2NCH2COOH ϩ H2C"CH2
s
p
(2)
(CH3)3N ϩ CO2
Table I Rate of Final (Pf) to Initial (Po) Pressure
Temperature
Substrate
(ЊC)
Po (Torr)
Pf (Torr)
Pf/Po
Average
3.23
N,N-Dimethylglycine ethyl ester
380.4
390.9
400.0
410.0
391.0
400.0
410.0
420.0
109
73
38
75
28
47
47
30
304.5
231
123
248.5
80
154
143
108
3.12
3.16
3.22
3.31
2.85
3.34
3.04
3.27
Ethyl 1-piperidineacetate
3.12

468
ENSUNCHO ET AL.
Table II Stoichiometry of the Reactions
N,N-Dimethylglycine ethyl ester at 380.8ЊC
Time (min)
4
10
18
25
30
Reaction (%) (pressure)
Ethylene (%) (GLC)
13.68
13.08
31.61
33.60
45.65
47.10
54.90
56.40
65.85
66.12
Ethyl 1-piperidineacetate at 400.8ЊC
Time (min)
5
8
12
18
24
Reaction (%) (pressure)
Ethylene (%) (GLC)
31.00
31.97
39.58
38.70
53.92
51.87
71.95
69.91
80.23
78.20
Table III Homogeneity of the Reaction
Ethyl 1-Piperidineacetate
S/V
According to the product formation of this substrate
in reaction (3), the final pressure Pf should be threefold
the initial pressure Po. The actual average experimen-
tal results of Pf /Po ϭ 3.12 (Table I). An additional
examination of the stoichiometry of reaction (3), up
to 80% decomposition, was possible by comparing
the pressure measurements with the quantitative gas
chromatographic analyses of the ethylene product
(Table II).
Ϫ
1 a
Ϫ
1 b
Ϫ1 c
Compound
(cm ) 104k1(s ) 104k1(s )
N,N-Dimethylglycine
ethyl ester at 390.8ЊC
Ethyl 1-piperidineace-
tate at 381.6ЊC
1
6
1
6
11.83
11.98
3.40
11.66
11.95
3.46
3.60
3.56
a S ϭ surface area; V ϭ volume.
b Clean Pyrex vessel.
c Vessel seasoned with allyl bromide.
N9CH2COOCH2CH3
N9CH2COOCH ϩ H2C"CH2
N9CH3 ϩ CO2
(3)
Table IV Effect of the Inhibitor Toluene on Ratesa
Substrate
Ϫ
1
Po (Torr)
Pi (Torr)
Pi/Po
104k1(s )
N,N-Dimethylglycine ethyl ester at 400.0ЊC
110
112
60
38
47
36.5
45
34
—
126
157.5
180.5
—
29
68
88
—
1.1
2.6
4.8
—
0.8
1.5
2.6
20.33
20.37
20.48
20.23
18.69
18.54
18.41
18.91
Ethyl 1-piperidineacetate at 410.0ЊC
a Po ϭ pressure of the substrate; Pi ϭ pressure of toluene inhibitor.

THE MECHANISM OF NEUTRAL AMINO ACID DECOMPOSITION IN THE GAS PHASE
469
Table VI Variation of Rate Coefficient with Temperature
N,N-Dimethylglycine ethyl ester
Temperature (ЊC) 360.8
2.19
370.5
3.93
380.1
6.89
389.0
10.24
400.0
20.35
410.0
35.47
Ϫ
1
104k1(s )
Ϫ1
Ϫ1
Ϫ1
Rate equation: log k1(s ) ϭ (13.01 Ϯ 3.7) Ϫ (202.3 Ϯ 0.3) kJ mol (2.303RT) ; r ϭ 0.9957
Ethyl 1-peperidineacetate
Temperature (ЊC)
381.6
3.90
391.6
6.87
400.0
11.17
410.0
18.38
420.0
31.88
430.6
54.18
Ϫ
1
104k1(s )
Ϫ1
Ϫ1
Ϫ1
Rate equation: log k1(s ) ϭ (12.91 Ϯ 0.31) Ϫ (204.4 Ϯ 0.1) kJ mol (2.303RT) ; r ϭ 0.9997
N,N-Dimethylglycine
Temperature (ЊC)
300.6
8.26
310.0
15.59
Ϫ
1
104k1(s )
Ϫ1
Ϫ1
Ϫ1
Rate equation: log k1(s ) ϭ (13.0) Ϫ (176.6) kJ mol (2.303RT)
The homogeneity of this elimination process was ex-
amined in a vessel with a surface-to-volume ratio six
times greater than that of the normal vessel. The
packed and unpacked clean and seasoned Pyrex ves-
sels showed no effect on the rate coefficients (Table
III). The pyrolysis of this substrate was not affected
by the addition of different proportions of the free rad-
ical inhibitor toluene (Table IV). No induction period
was observed. The rate coefficients are reproducible
with a relative standard deviation not greater than 5%
at a given temperature. The rate coefficient of ethyl 1-
piperidineacetate, calculated from k1 ϭ (2.303/t)
log[2Po/(3Po Ϫ Pt)] was found to be independent of
the intial pressure (Table V), and the first-order plots
are satisfactorily linear up to 75% reaction. The vari-
ation of the rate coefficient with temperature is shown
in Table VI. The data were fitted to the Arrhenius
equation, where the k-values at the 90% confidence
level obtained from the least-squares procedure are
given.
N,N-Dimethylglycine
Carrying out the usual systematic examinations for the
stoichiometry (4), for the homogeneity and for the ef-
fect of the free radical suppressor toluene, this acid
was found to be difficult for complete kinetic work.
Only at 300.6 and 310.0ЊC did it show a first-order
elimination [reaction (4)] with a rate k ϭ 8.26 ϫ 10Ϫ
4
1
sϪ1 and 15.19 ϫ 10Ϫ4 sϪ , respectively.
(CH3)NCH2COOH !: (CH3)3N ϩ CO2 (4)
With these two rate coefficients and by assuming a
frequency factor of 1013 sϪ1 for a five-membered cyclic
transition state mechanism in the gas phase, it is pos-
sible to estimate the Arrhenius expression as given in
Table VI.
The data in Table VII reveals that N,N-dimethyl-
glycine ethyl ester is about 1.8 times faster in rate than
ethyl 1-piperidine acetate at 400ЊC. This small but sig-
nificant difference in rate suggests that the electron-
release of the cyclic methylene chain containing the
nitrogen atom decreases the electron-withdrawing ef-
fect of the piperidine group, thus lowering the rate of
elimination relative to the (CH3)2N group. According
to the results of the present work, the ethyl esters of
these amino acids proceed via a mechanism similar to
carboxylic esters in the gas phase. This means through
a six-membered cyclic transition state as depicted in
reaction (5).
Table V Variation of Overall Rate Coefficients with
Initial Pressure
N,N-Dimethylglycine ethyl ester at 380.1ЊC
Po (Torr)
14
6.83
Ethyl 1-piperidineacetate at 400.0ЊC
21
6.98
32
6.78
41
6.61
50
6.90
Ϫ
1
104k1(s )
Po (Torr)
12
10.93
29
11.48
41
11.17
69
11.03
78
11.24
Ϫ
1
104k1(s )
Table VII Kinetic and Thermodynamic Parameters at 400.0ЊC
Ϫ
1
Ϫ
1
ꢀ
ꢀ
ꢀ
Substrate
104k1(s ) Ea (kJ/mol)
log A(s )
⌬S (J/mol K) ⌬H (kJ/mol) ⌬G (kJ/mol)
N,N-Dimethylglycine ethyl ester
Ethyl 1-piperidineacetate
N,N-Dimethylglycine
20.42 202.3 Ϯ 0.3 13.01 Ϯ 3.7
11.10 204.4 Ϯ 0.1 12.91 Ϯ 0.3
Ϫ10.98
Ϫ12.90
Ϫ11.17
196.7
198.7
171.0
204.1
207.4
178.5
1963.7
176.6
13.00

470
ENSUNCHO ET AL.
‡
H
O
O
O
CH2
CH2
O
NCH29C9OCH2CH3
NCH29C
NCH29C9OH ϩ H2C"CH2
‡
‡
CH2
dϩ
dϪ
O
9CO2
N9CH2
N
H
C
NCH3
H
O
(5)
The corresponding neutral amino acid intermediate
appears to be, under the conditions of the reactions, a
very reactive species due to the high nucleophilicity
of the nitrogen atom. Apparently, the N atom becomes
more polarized when it is approached by the acidic H
of the COOH group, thus causing a lowering in the
energy. Consequently, an extremely faster decompo-
sition process occurs. This amine substituent is not a
leaving group like the 2-substituents described in re-
action (1). The former undergoes a rapid decarboxyl-
ation [reaction (5)], while the latter is a slower decar-
bonylation process [reaction (1)].
In considering the mechanism for the fast decom-
position of these neutral amino acid intermediates, the
elimination kinetics of N,N-dimethylglycine, the in-
termediate of N,N-dimethylglycine ethyl ester pyrol-
ysis, is found to be approximately 96 times faster than
the corresponding ethyl ester at 400ЊC (Table VII).
This means that (CH3)2NCH2COOH must have de-
composed rapidly at the working temperature of the
ethyl ester. Therefore, the gas-phase pyrolytic elimi-
nation of neutral amino acids in general must take
place at very low temperatures. According to these
considerations, N,N-dimethylglycine decomposes
through a mechanism of a five-membered cyclic tran-
sition state for decarboxylation [reaction (6)].
In conclusion, the results of this work appear to
support the theoretical consideration of Ding and
Krogh-Jespersen [13] that glycine does not exist in the
gas phase. In this respect, N,N-dimethylglycine ap-
pears to decompose as a neutral molecule. Moreover,
organic molecules containing a N atom at the ␣-po-
sition of carboxylic acid is not a leaving group like
other substituents described in reaction (1).
We are grateful to the Consejo Nacional de Investigaciones
Cient´ıficas y Tecnolo´gicas of Venezuela (CONICIT) Project
No. S1-97000005 and to the Instituto Colombiano para el
Desarrollo de la Ciencia y Tecnolog´ıa (COLCIENCIAS)
Project No. 1118-05-606-96 for financial support.
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O
ϩ
Ϫ
(CH3)2NCH2C
(CH3)2NCH2C
O
(CH3)2NCH2 ϩ CO2
ϩ
Od
dϪ
H
H
O
H
(CH3)3N
(6)

THE MECHANISM OF NEUTRAL AMINO ACID DECOMPOSITION IN THE GAS PHASE
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