Kinetics and mechanism of thermal gas-phase elimination of α- and β- (N-arylamino)propanoic acid: Experimental and theoretical analysis

Article abstract of DOI:10.1016/j.tet.2004.01.087

2-(N-Phenylamino)propanoic acid 1a and 3-(N-phenylamino)-propanoic acid 2a together with four of their aryl analogues were pyrolysed in the gas-phase. The reactions were homogeneous and free from catalytic and radical pathways. Analysis of the pyrolysate of 1 showed the elimination products to be carbon monoxide, acetaldehyde and aniline, while the pyrolysate of 2 reveals the formation of acrylic acid in addition to aniline. Theoretical study of the pyrolysis of 2 using an ab initio SCF method lend support to a reaction pathway involving a 4-membered cyclic transition state.

Full text of DOI:10.1016/j.tet.2004.01.087

Tetrahedron 60 (2004) 3045–3049
Kinetics and mechanism of thermal gas-phase elimination of
a- and b- (N-arylamino)propanoic acid: experimental and
theoretical analysis
*
Sundus A. Al-Awadi, Mariam R. Abdallah, Mohamad A. Hasan and Nouria A. Al-Awadi
Department of Chemistry, Kuwait University, PO Box 5969, Safat 13060, Kuwait
Received 20 October 2003; revised 5 January 2004; accepted 29 January 2004
Abstract—2-(N-Phenylamino)propanoic acid 1a and 3-(N-phenylamino)-propanoic acid 2a together with four of their aryl analogues were
pyrolysed in the gas-phase. The reactions were homogeneous and free from catalytic and radical pathways. Analysis of the pyrolysate of 1
showed the elimination products to be carbon monoxide, acetaldehyde and aniline, while the pyrolysate of 2 reveals the formation of acrylic
acid in addition to aniline. Theoretical study of the pyrolysis of 2 using an ab initio SCF method lend support to a reaction pathway involving
a 4-membered cyclic transition state.
q 2004 Elsevier Ltd. All rights reserved.
1. Introduction
p-chlorophenyl for 1c and 2c p-methylphenyl group.
We have recently reported on the kinetics and mechanism of
thermal gas-phase elimination of a-substituted carboxylic
acids, namely 2-phenoxypropanoic acid together with five
of its aryl derivatives; phenylthio and N-phenylamino
analogues were also investigated.1 The reaction pathway
is considered to involve a cyclic five-membered transition
state associated with elimination of HX and formation of an
a-lactone intermediate (Scheme 1). The effect of the
a-substituent (X) is related to the basicity of X.
2. Results and discussion
2.1. Kinetics
Percent (10–20%) pyrolysis at the reaction temperature is
used to evaluate the rate constant of reaction on the basis of
HPLC retention data. Each recorded rate constant represents
an average from at least three kinetic runs, which are in
agreement to within ^2%. Rate coefficients were deter-
mined at different temperatures of 5–10 8C intervals for
$95% reaction. The kinetic measurements of each substrate
were followed over a temperature range of .50 K, an
experimental requirement in thermal gas-phase elimination
studies. The homogeneity of the reaction was tested by
comparing the kinetic rate using an empty carbonized tube
with that of similar vessel packed with glass helices. The
results show that no pyrolysis occurred due to activation at
the reactor surface. Since six-fold change in the amount of
substrate used per kinetic run gave no significant change in
rate coefficient, these reactions were deemed to be of first
order. The presence or absence of a radical mechanism was
Scheme 1.
In this study, we look at the pyrolysis reaction of 2-(N-
arylamino)propanoic acid 1a–c and 3-(N-arylamino)pro-
panoic acid 2a–c; the two systems are a- and b-derivatives
of propanoic acid. Substituents which make up the aryl
moiety for 1a and 2a, phenyl group; for 1b and 2b,
Keywords: a- and b- (N-Arylamino)propanoic acid; Thermal gas-phase
elimination; Theoretical analysis.
*
Corresponding author. Tel.: þ965-4845098; fax: þ965-4836127;
e-mail address: nouria@kuc01.kuniv.edu.kw
0040–4020/$ - see front matter q 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2004.01.087

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S. A. Al-Awadi et al. / Tetrahedron 60 (2004) 3045–3049
Table 1. Rate coefficients and Arrhenius parameters for pyrolysis of 1a–c
and 2a–c
summarized in Table 1. The rates at 600 K are calculated
using the kinetic equation for first order reactions:
Compound
T
(K)
104 k
(s21
Log A
(s21
Ea
(kJ mol21
103 k600 K
(s21
log k ¼ log A 2 Ea=4:575 T
)
)
)
)
1a
550.50
560.85
570.75
572.05
591.65 30.03
602.15 53.38
2.320 12.13^0.50 166.18^6.12 3.68
The noteworthy observation in this kinetic study is that in
the earlier paper1 we reported reactivity correlations for a-
substituents in propanoic acid in which the order of
reactivity of the aryl groups was: –NHPh .–OPh.–
SPh. On the basis of re-evaluation of the rate constant of
2-(N-phenylamino)propanoic acid, the order now is: –OPh
.–SPh.–NHPh. This order corresponds more closely to
the trend expected from the nature of the incipient phenol,
thiophene and aniline fragments. It is of interest to note that
there seems to be no opposing substituent effect from the
p-position of the aryl moiety of the amino group consistent
with the electron-donating character of the methyl and the
electron-withdrawing character of the chloro substituent.
The pyrolysates from the complete gas-phase pyrolysis of
a-substituted carboxylic acids [2-(N-arylamino)propanoic
acid 1a–c] and b-substituted carboxylic acids [3-(N-
arylamino)propanoic acid 2a–c] were analysed and their
constituents fully characterized using LC retention data, MS
and NMR techniques.
4.640
9.070
9.810
1b
1c
548.50
552.55
570.65
589.05 20.75
606.75 46.72
2.320 10.04^0.15 143.58^1.64 6.63
2.890
7.930
475.55
516.15
537.05
556.35 18.29
576.55 31.40
596.85 57.54
0.900
4.210
8.990
4.86^0.09
81.21^1.01 5.47
2a
2b
2c
547.50
558.65
568.55
578.55 13.88
589.05 23.46
605.50 46.10
3.260
5.720
9.080
8.53^0.34 125.96^3.63 4.64
The pyrolysates from substrates 1a–c were ascertained to
be ArNH2, CH3CHO and CO. The reaction pathway shown
in Scheme 1 is compatible with the products of pyrolysis
from 1a–c and follows earlier findings by us and others.4–7
540.50
543.65
557.35 10.34
567.75 14.15
581.95 31.90
590.50 44.33
4.320
5.010
8.68^0.61 124.77^6.70 3.46
The pyrolysates from the pyrolytic reaction of substrates
2a–c were identified as ArNH2 and acrylic acid. A plausible
mechanism is outlined in Scheme 2 to account for the
formation of acrylic acid and substituted anilines from the
pyrolysis of 2a–c. This proposed pathway proceeds either
through a six-membered transition state (route i) or through
a four-membered transition state (route ii). Elimination of
aniline in route (i) involves the acidic proton of the
carboxylic group, while in route (ii) it involves the less
acidic proton of the a-carbon atom.
506.25
519.45
532.05
544.45 11.55
569.95 28.54
4.060
6.080
9.130
3.93^0.41
71.17^5.47 6.21
also tested by adding a radical trap, the presence of
cyclohexene which was used in this test had no effect on
the rate.2,3 Arrhenius plots of log k vs 1/T (K) showed strict
linearity up to .90% reaction. Kinetic data, Arrhenius
parameters, and rate coefficients of reaction at 600 K are
Examining and characterizing in detail both routes
(Scheme 2) in the suggested mechanism was carried out
Scheme 2.

S. A. Al-Awadi et al. / Tetrahedron 60 (2004) 3045–3049
3047
by theoretical calculation of the thermal elimination of
aniline and acrylic acid from substrate 2a using ab initio
SCF method.
2.2. Computational studies
Theoretical studies on the thermolysis of b-substituted
carboxylic acids in the gas phase were carried out using an
ab initio SCF method. Calculations were carried out to
explore the nature of the reaction mechanism of the
unimolecular decomposition of molecule 2a. Two competi-
tive reaction pathways for the decomposition process have
been studied. All the calculations have been performed with
the TITAN computational package.8
Figure 1. Schematic representation of optimized structure of 2a to show
˚
main distances (A), obtained by HF/6-31G* basis set.
The geometric parameters of the substrate 2a, the transition
states A and B, were fully optimized at the HF/6-31G* level
to obtain the energy profile corresponding to the studied
reaction. Each stationary structure characterized by
frequency calculations was a minimum or saddle point of
first-order. A scaling factor of 0.9135 for the zero-point
vibrational energies has been used.9 The structures obtained
from the optimization calculations are represented in
Figures 1–3.
Figure 2. Schematic representation of the optimized structure of TS-AI to
˚
show main distances (A) obtained by HF/6-31G*.
Table 2 shows the main distances in each optimized
structure. During the thermolysis process, when 2a is
being transformed into TS-AII, the N1–C2 and C3–C4
distances are increasing, whereas the C2–C3 and N1–H7
distances are decreasing.
Electronic energies, zero-point vibrational energies, enthal-
pies and entropies were evaluated at the HF/6-31G* level of
theory for the substrate 2a, TS-AI and TS-AII, and the
products involved in the two pathways of the studied
reaction are collected in Table 3.
Figure 3. Schematic representation of the optimized structure of TS-AII, to
˚
show main distances (A), obtained by HF/6-31G* basis set.
The free energy profile for the decomposition process of the
studied reaction is re-presented in Figure 4, obtained at the
HF/6-31G* level.
˚
Table 2. Main distances (A) in the substrate 2a and transition states (AI,
AII), calculated at the HF/6-31G* level
˚
Distance, A
2a
TS-AI
TS-AII
Examination of the free energy of the two suggested
transiting states shows that TS-AII has a lower free energy
barrier than TS-AI (Fig. 4). The calculated activation free
energies are 89.59 and 66.41 kJ mol21 for the reaction via
the transition states TS-AI and TS-AII, respectively. The
overall process is exergonic; with reaction free energy equal
N1–C2
C2–C3
C3–C4
C3–H7
C4–O8
C4–O5
O5–H6
N1–H7
N1–H6
O8–H7
1.446
1.532
1.505
1.085
1.189
1.330
0.953
2.770
5.631
3.102
1.477
1.514
1.453
1.523
1.251
1.286
0.965
3.916
2.020
1.208
1.517
1.512
1.438
1.550
1.215
1.337
0.951
1.235
4.638
2.705
to 292.89 kJ mol21
.
From the results obtained, it appears that the single cyclic
4-membered ring transition state, TS-AII, is more
favored than the cyclic 4- and 6-membered ring transition
state, TS-AI.
Table 3. Total energy zero-point vibrational energy (ZPE) and thermal correction to enthalpy and entropy at HF/6-31G* and 573 K for 2a, transition states and
products
Species
Total energy (Hartrees)
ZPE (kcal mol21
)
Enthalpy (kcal mol21
)
Entropy (cal mol21 K21
)
2a
TS-AI
TS-AII
PhNH2
H2CvCHCOOH
2551.410335
2551.266869
2551.301672
2285.730756
2265.653665
127.988
124.854
125.137
78.870
134.533
130.937
131.305
82.269
104.899
99.273
100.440
74.352
70.635
45.866
48.866

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S. A. Al-Awadi et al. / Tetrahedron 60 (2004) 3045–3049
Figure 4. Free energy profile evaluated at the HF/6-31G* level for 2a decomposition process.
3. Experimental
2-(4-Chlorophenylamino)propanoic acid, 1b White crys-
tals, mp 143 8C. 1H NMR (acetone-d6): d 1.47 (d, J¼6.9 Hz,
3H, CH–3), 4.1 (q, J¼6.9 Hz, 1H, CH), 6.67 (d, J¼8.6 Hz,
2H, ArH), 7.11 (d, J¼8.6 Hz, 2H, ArH). 13C NMR (CDCl3):
d 19.2, 52.6, 115.1, 124.1, 129.7, 145.2, 177.9. Anal. calcd
for C9H10NO2Cl:, 54.13; H, 5.01; N, 7.02. Found: C, 54.0;
H, 5.16; N, 7.03%. MS: m/z 199 (Mþ). IR (cm21): 3400
(NH), 1592 (CO).
3.1. Synthesis
3.1.1. Ethyl 2-arylaminopropionate. A mixture of ethyl
2-bromopropionate (0.10 mol), aniline or its p-substituted
analogues (0.10 mol) and sodium acetate (0.20 mol) was
refluxed at 125 8C for 12 h. The reaction mixture was
cooled, filtered free of the salt and repeatedly washed with
ether. The ether was removed in vacuo and the remaining
product was distilled to afford the title compounds.10
2-(p-Methylphenylamino)propanoic acid, 1c. Light brown
crystals, mp 142 8C. 1H NMR (acetone-d6): d 1.45 (d,
J¼6.9 Hz, 3H, CH3), 2.18 (s, 3H, CH3), 4.07 (q, J¼6.9 Hz,
1H, CH), 6.58 (d, J¼8.2 Hz, 2H, ArH), 6.93, (d, J¼8.2 Hz,
2H, ArH). 13C NMR (CDCl3): d 19.0, 21.0, 54.4, 115.3,
129.6, 130.4, 143.6, 179.3. Anal. Calcd. For C10H13NO2: C,
67.03; H, 7.26; N, 7.82. Found: C, 67.39; H, 7.26; N, 8.06%.
MS: m/z 179.1 (Mþ). IR (cm21): 3436 (NH), 1579 (CO).
3.1.2. 2-Arylaminopropanoic acid, 1a–c. Ethyl 2-aryl-
aminopropionate was hydrolysed by heating under reflux
with 10% aqueous sodium hydroxide solution (100 ml) for
4–5 h. After cooling, the product was acidified by dropwise
addition of diluted hydrochloric acid, the crystals of the
products were filtered and recrystallized from ethyl
acetate and petroleum ether to afford the title compounds
in 55–75% yield. The following compounds were thus
synthesized.
3.1.3. Preparation of 3-arylaminopropanoic acid, 2a–c.
To a 10% aqueous solution of NaOH (60 ml) was added 5 g
of 3-aminoaryl propionitrile11 and the mixture was heated
under reflux for 6 h. The reaction was then cooled and
acidified cautiously by dropwise addition of glacial acetic
acid. The acidified solution was then extracted with ethyl
acetate; the extract was dried and concentrated under
vacuum to afford scales of product which were crystallized
from petroleum ether-ether to afford.
2-Phenylaminopropanoic acid, 1a. Light brown crystals,
1
mp 165.5 8C. H NMR (acetone-d6): d 1.47 (d, J¼7.2 Hz,
3H, CH3), 4.12 (q, J¼7.2 Hz, 1H, CH), 6.62–6.68 (m, 3H,
ArH), 7.12 (t, J¼7.2 Hz, 2H, ArH). 13C NMR (CDCl3): d
19.3, 52.9, 115.6, 119.6, 129.8, 146.5, 177.6. Anal. calcd for
C9H11NO2: C, 65.45; H, 6.66; N, 8.48. Found: C, 64.95; H,
6.61; N, 8.6%. MS: m/z 165 (Mþ). IR (cm21): 3420 (NH),
1570 (CO).
3-Phenylaminopropanoic acid, 2a. Greenish crystals, mp
1
70.5 8C. H NMR (acetone-d6): d 2.62 (t, J¼6.8 Hz, 2H,

S. A. Al-Awadi et al. / Tetrahedron 60 (2004) 3045–3049
3049
CH2–CO), 3.43 (t, J¼6.8 Hz, 2H, CH2–NH), 6.61 (d,
3.3. General procedure for product analysis
J¼7.6 Hz, 2H, ArH), 6.67 (t, J¼7.6 Hz, 1H, ArH), 7.12 (t,
J¼7.6 Hz, 2H, ArH). 13C NMR (CDCl3): d 34.0, 39.8,
113.8, 118.6, 129.8, 147.6, 177.8. Anal. Calcd. for
C9H11NO2: C, 65.45; H, 6.6; N, 8.48. Found: C, 65.09; H,
6.55; N 8.6%. MS: m/z 165 (Mþ). IR (cm21) 3407 (NH),
1682 (CO).
The apparatus used for this purpose was the same pyrolysis
unit used for kinetic studies. Each of the substraters (0.2 g)
was introduced in the reaction tube, cooled in liquid
nitrogen, sealed under vacuum and placed in the pyrolyzer
for 900 s at a temperature comparable to that used for
complete pyrolysis in the kinetic studies. The contents of the
tube were then analysed by NMR and LC/MS and the yield
was determined by HPLC with reference sample (Table 4).
The spectral data of the pyrolysates were compared with
their reference spectra.
3-(p-Chloroanilino)propanoic acid, 2b. Light brown crys-
tals, mp 125 8C, 1H NMR (acetone-d6): d 2.62 (t, J¼6.8 Hz,
2H, CH2), 3.41 (t, J¼6.8 Hz, 2H, CH2), 6.67 (d, J¼6.8 Hz,
2H, Ar H), 7.11 (d, J¼6.8 Hz, 2H, ArH). 13C NMR
(CDCl3): d 34.1, 40.0, 114.9, 123.3, 129.8, 146.4, 177.8.
Anal. Calcd. for C9H10NO2: C, 54.13; H, 5.01; N, 7.01.
Found: C, 54.5; H, 5.07; N, 7.07%. MS: m/z¼199 (Mþ), IR
(cm21): 3424 (NH), 1708 (CO).
Table 4. Product analysis of compounds 1a–c and 2a–c
Cpd
T (K)
Pyrolysates and yields (%)
1a
1b
1c
2a
2b
2c
630
620
600
630
620
600
Aniline (52%)
Acetaldehyde (42%)
Acetaldehyde (38.3%)
Acetaldehyde (12%)
Acrylic acid (25.9%)
Acrylic acid (30.6%)
Acrylic acid (35.6%)
p-Chloroaniline (33.7%)
p-Tolylaniline (26.4%)
Aniline (18.6%)
p-Chloroaniline (49.9%)
p-Tolylaniline (33.6%)
3-(p-Methylphenylmino)propanoic acid, 2c. Brown crystals,
mp 85.5 8C, 1H NMR (acetone-d6): 2.18 (s, 3H, CH3), 2.59
(t, J¼6.8 Hz, 2H, CH2), 3.38 (t, J¼6.8 Hz, 2H, CH2), 6.57
(d, J¼8.4 Hz, 2H, Ar H), 6.93 (d, J¼8.4 Hz, 2H, ArH). 13C
NMR (CDCl3): d 21.0, 34.1, 40.5, 114.4, 128.4, 130.4,
145.3, 177.8. Anal. Calcd. for C10H13NO2: C, 67.03; H,
7.26; N, 7.82. Found: C, 66.75; H, 7.24; N, 7.99%. MS: m/z
179.1 (Mþ). IR (cm21): 3364 (NH), 1684 (CO).
Acknowledgements
The support of the University of Kuwait received through
research grants # GS01/01 and GS03/01 for the facilities of
ANALAB/SAF is highly acknowledged.
3.2. Kinetic runs and data analysis
Stock solution (7 ml) is prepared by dissolving 6–10 mg of
the substrate in acetonitrile as solvent to give a concen-
tration of 1000–2000 ppm. Internal standard is then added,
the amount of which is adjusted to give the desired peak area
ratio of substrate to standard (2.5:1). The solvent (aceto-
nitrile) and the internal standard (chlorobenzene) were
selected because both are stable under the conditions of
pyrolysis, and because they do not react with either substrate
or product. Each reaction mixture is filtered to ensure that a
homogeneous solution is obtained.
References and notes
1. Al-Awadi, N.; Kaul, K.; El-Dusouqui, O. J. Phys. Org. Chem.
2000, 13, 499–504.
2. Al-Awadi, N.; El-Dusouqui, O.; Int, J. Chem. Kinet. 1997, 29,
295–298.
3. Al-Awadi, N.; Al-Bashir, R.; El-Dusouqui, O. J. Chem Soc.,
Perkin Trans. 2 1989, 579–581.
The weight ratio of the substrate with respect to the internal
standard is calculated from the ratio of the substrate peak
area to the peak area of the internal standard. The kinetic
rate was obtained by tracing the rate of disappearance of the
substrate with respect to the internal standard as follows.
4. Chuchani, G.; Rotinov, A. Int. J. Chem. Kinet. 1989, 21,
367–371.
5. Chuchani, G.; Martin, I.; Rotinov, A.; Dominiguzz, R. M. Int.
J. Chem. Kinet. 1991, 23, 779–783.
6. Chuchani, G.; Martin, I.; Rotinov, A.; Dominguzz, R. M.
J. Phys. Org. Chem. 1993, 6, 54–58.
An aliquot (0.2 ml) of each solution containing the substrate
and the internal standard was pipetted into the reaction tube
which was then placed in the pyrolyzer for 6 min under non-
thermal conditions. A sample was then analyzed using the
HPLC probe with the UV detector at wavelength of 256 nm,
and the standardization value (A0) was calculated. Several
HPLC measurements were obtained with an accuracy of
$2%. The temperature of the pyrolysis block was then
raised until approximately 10% pyrolysis was deemed to
occur over 900 s. This process was repeated after each 10–
15 8C rise in the temperature of the pyrolyzer until $90%
pyrolysis occurred. The relative ratios of the integration
values of the sample and the internal standard (A) at the
pyrolysis temperature was then calculated. A minimum of
three kinetic runs were carried out at each 10–15 8C rise in
the temperature of the pyrolyzer to ensure reproducible
values of (A). Treatment of the kinetic data has been
detailed elsewhere.12–14
7. Chuchani, G.; Martin, I.; Rotinov, A.; Dominguzz, R. M. Int.
J. Chem. Kinet. 1995, 27, 849–853.
8. Titan, Tutorial and User’s Guide, Wavefunction, Inc.: 18401
Von Karman Avenue, USA, 1999..
9. Scott, A.; Radom, L. J. Phys. Chem. 1996, 100, 16502–16513.
10. Szulc, Z.; Mlochowski, J.; Pauls, J. J. Prakt. Chem. 1988, 330,
1023–1029.
11. Organic Synth.; Rabjohn, E., Ed.; Wiley: London, 1963;
Collect. Vol. 4, p 205.
12. Al-Awadi, N. A.; Elnagdi, M. H.; Kaul, K.; Ilingovan, S.; El-
Dusouqui, O. M. E. J. Phys. Org. Chem. 1999, 12, 654–656.
13. Al-Awadi, N. A.; El-Dusouqui, O. M. E.; Kaul, K.; Dib, H. H.
Int. J. Chem. Kinet. 2000, 32, 403–407.
14. Al-Awadi, N. A.; Kaul, K.; El-Dusouqui, O. M. E. J. Phys.
Org. Chem. 2000, 13, 499–504.