Kinetics and mechanism of gas-phase pyrolysis of N-aryl-3-oxobutanamide ketoanilides, their 2-arylhydrazono derivatives, and related compounds

Article abstract of DOI:10.1002/kin.20220

Rates and products of reaction and Arrhenius activation parameters were determined for the gas-phase thermolysis of 14 substrates of the title compounds using sealed pyrex reactor tubes and HPLC/UV-VIS to monitor substrate pyrolysis. The 14 compounds under study are N-phenyl-3-oxo- (1), N-(p-chlorophenyl)-3-oxo- (2). N-(p-methylphenyl)-3-oxo- (3). and N-(p-methoxyphenyl)-3-oxobutanamide (4). in addition to (i) four substrates (5-8) obtained by the replacement of the pairs of methylene hydrogens at the 2-position of compounds (1-4), each pair by a phenylhydrazono group; (ii) three arylhydrazono derivatives (9-11) in which Cl, CH₃, or OCH₃ groups are substituted at the para position of the phenylhydrazono moiety of compound 5, (iii) 3-oxobutanamide (acetoacetamide. 12), N-phenyl-3-oxo-3- phenylpropanamide (13), and N,N′-diphenylpropanediamide (14). The reactions were conducted over 374-546 K temperature range, and the values of the Arrhenius log A(s^-1) and E_a(kJ mol^-1) of these reactions were, respectively, 120±2.0 and 119.2 ± 17.0 for the ketoanilides (1-4, 12-14), and 13.0 ± 0.7 and 157.5 ± 8.6 for the arylhyrazono compounds (5-11). Kinetically. the arylhydrazono derivatives were found to be ca. 1.4 × 10³ to 5.7 × 10³ times less reactive than the parent ketoanilides. A mechanism is proposed to account for reaction products and to rationalize molecular reactivities.

Full text of DOI:10.1002/kin.20220

Kinetics and Mechanism of
Gas-Phase Pyrolysis of
N-Aryl-3-oxobutanamide
Ketoanilides, Their
2-Arylhydrazono
Derivatives, and Related
Compounds
RANA N. MALHAS, NOURIA A. AL-AWADI, OSMAN M. E. EL-DUSOUQUI
Chemistry Department, Kuwait University, P.O. Box 5969, Safat 13060, Kuwait
Received 6 April 2006; revised 8 July 2006; accepted 6 October 2006
DOI 10.1002/kin.20220
Published online in Wiley InterScience (www.interscience.wiley.com).
ABSTRACT: Rates and products of reaction and Arrhenius activation parameters were deter-
mined for the gas-phase thermolysis of 14 substrates of the title compounds using sealed pyrex
reactor tubes and HPLC/UV-VIS to monitor substrate pyrolysis. The 14 compounds under study
are N-phenyl-3-oxo- (1), N-(p-chlorophenyl)-3-oxo- (2), N-(p-methylphenyl)-3-oxo- (3), and
N-(p-methoxyphenyl)-3-oxobutanamide (4), in addition to (i) four substrates (5–8) obtained
by the replacement of the pairs of methylene hydrogens at the 2-position of compounds (1–4),
each pair by a phenylhydrazono group; (ii) three arylhydrazono derivatives (9–11) in which Cl,
CH3, or OCH3 groups are substituted at the para position of the phenylhydrazono moiety of com-
pound 5; (iii) 3-oxobutanamide (acetoacetamide, 12), N-phenyl-3-oxo-3-phenylpropanamide
(13), and N,Nꢀ-diphenylpropanediamide (14). The reactions were conducted over 374–546 K
temperature range, and the values of the Arrhenius log A(s−1) and Ea(kJ mol−1) of these
reactions were, respectively, 12.0 2.0 and 119.2 17.0 for the ketoanilides (1–4, 12–14), and
Correspondence to: Nouria A. Al-Awadi; nouria@kuc01.kuniv.
edu.kw.
Contract grant sponsor: ANALAB.
Contract grant number: GS 01/01.
Contract grant sponsor: SAF.
Contract grant number: 03/01.
2006 Wiley Periodicals, Inc.
c
ꢀ

KINETICS AND MECHANISM OF GAS-PHASE PYROLYSIS OF N-ARYL-3-OXOBUTANAMIDE KETOANILIDES
83
13.0 0.7 and 157.5 8.6 for the arylhyrazono compounds (5–11). Kinetically, the arylhydra-
zono derivatives were found to be ca. 1.4 × 103 to 5.7 × 103 times less reactive than the parent
ketoanilides. A mechanism is proposed to account for reaction products and to rationalize
molecular reactivities. ꢁ 2006 Wiley Periodicals, Inc. Int J Chem Kinet 39: 82–91, 2007
C
arylhydrazono derivatives, and compares these find-
ings with relevant data on 1,3-diketones and analogous
cyanoketones and their arylhydrazono derivatives [16].
The results indicate that the arylhydrazono group has
opposite effects on the reactivity of these two systems.
The group enhances the reactivity of the ketones, while
decreasing that of the ketoamides, in each case by a
large rate factor. NMR and IR studies have drawn at-
tention to the importance of H-bond interactions in-
volving the oxygen of the ketone carbonyl (CO) group
and the (H) of the arylhydrazono (NH) moiety, as well
as the effect of substituents on the strength of these
interactions [17,18]. In the case of the ketoamides, the
carbonyl oxygen is also susceptible to interaction with
the (H) of the amide (NH) moiety.
INTRODUCTION
Studies on ketoanilides and thione analogues have
shown that these compounds pyrolyse into organic iso-
cyanates and isothiocyanates [1,2]. The reactions are
considered to proceed through a cyclic six-membered
transition state (TS) [2,3]. Generally, flow and static
and flash vacuum pyrolysis (FVP) techniques provide
useful strategies in synthesis, and the importance of
FVP in this respect has been emphasized [4–6]. Be-
sides, gas-phase pyrolytic reactions, which involve no
solvents, reagents, or catalysts, are increasingly being
used as atom-efficient and environmentally desirable
pathways to clean functional group transformation and
synthesis of novel heterocycles [6–8]. It is noteworthy
that under these reaction conditions, molecular reac-
tivities depend solely on the structure of the substrate
and the effects of its substituents, and could, there-
fore, be deemed intrinsic. In addition, these same char-
acteristics make these thermal gas-phase elimination
reactions ideal models for theoretical investigations
[8–12]. It is of interest to note that experimental results
on activation barriers, TSs, and rate constants have
been confirmed by theoretical calculations for a num-
ber of thermal gas-phase reactions including pyroly-
sis of oximes, amides, hydroxyl ketones, anhydrides,
and ketoesters [8–15a,b]. In these studies the proposed
mechanisms were concerted asynchronous processes
involving a cyclic six-membered TS (Scheme 1), and
molecular reactivities were reported to be a function
of the H-bond donor acidity of the H X bond (i), the
polarity of the A B bond (ii), the protophilicity of the
YZ multiple bond (iii), or an effect combining two or
all of the three bonds (Scheme 1). Reactivity might
additionally be subject to the thermodynamic stability
of the incipient elimination fragments [8,16].
EXPERIMENTAL
General
Melting points were recorded on a Shimadzu–
Gallenkamp apparatus and are uncorrected. Elemental
analysis was by means of a LECO CHNS Elemen-
tal Analyzer. The GC-MS/EI analysis was made us-
ing a Finnigan MAT INCOSXL GC/MS mode, and
the HNMR spectra were recorded at 80 MHz on a
Bruker AC80 FT-NMR spectrometer, with CDCl3 as
solvent and TMS internal standard. The HPLC anal-
ysis was performed using a Metrohm HPLC (pump
model 7091C and SHIMADZU SPD-10 UV/VIS de-
tector), and Suppelco ABZ+ LC-8 chromatography
column (2.5-cm length and 4.6-mm ID, for 5-µm sam-
ple). The reactor used for kinetic and product analy-
sis is a Chemical Data System (CDS) custom-made
pyrolyzer consisting of an insulated aluminum-alloy
block fitted with a platinum resistance thermocouple
connected to a Comark microprocessor thermometer
for reactor temperature read-out, accurate to <0.5◦C.
The alloy was chosen for its high thermal conductivity
and low-temperature gradient, and may be heated for
up to 530◦C. The temperature of the reactor is con-
trolled by means of a Eurotherm 093 precision temper-
ature regulator to provide 0.1◦C incremental change.
The reaction tubes were Pyrex: 8 cm long for kinetic
runs, and 12 cm for product analysis; with internal and
outer diameters of 1.5 and 1.7 cm, respectively, for
both tubes.
The present study examines the results of the
kinetic and product analysis of the thermal gas-phase
elimination reaction of seven ketoamides and seven
A
X
(i)
(ii)
B
heat
H
A
X + [B
Y
ZH
HB
Y
Z]
Y
Z
(iii)
Scheme 1 Cyclic six-membered TS involving proton trans-
fer leading to molecular fragmentation.
International Journal of Chemical Kinetics DOI 10.1002/kin

84
MALHAS, AL-AWADI, AND EL-DUSOUQUI
Compounds 1–11, 13, and 14 were prepared fol-
Synthesis
lowing literature procedures [18], and compound 12
(acetoacetamide) was commercially available from
Aldrich: mp = 54–56◦C. All the compounds were
solids, and were recrystallized from either ethanol or
petroleum ether.
Synthesis of ketoanilides 1–4, 13 [21] from the re-
action of equimolar amounts of ethyl acetoacetate or
ethyl 3-phenylpropanoate with aniline or an appropri-
ate derivative. The reaction mixture was refluxed for
10–15 min (glycerol bath at 180◦C), cooled to room
temperature, and the solid thus obtained was then re-
crystallized from the appropriate solvent.
Kinetic Runs and Data Analysis
Synthesis of phenylhydrazono ketoanilides 5–8
[22,23] from the reaction of equimolar amounts of the
appropriate acetoacetarylide (0.01 mol) with phenyl-
diazonium salt (0.01 mol) in the presence of sodium
acetate (8 g) and ethanol (100 mL). The resulting
solid was washed with water, and recrystallized from
ethanol.
Synthesis of arylhydrazono ketoanilides 9–11
[18,22–24] from the reaction of equimolar amounts
of acetoacetanilide with the appropriate aryldiazonium
salt as described above.
Stock solution (7 mL) was prepared by dissolving
5–10 mg of the substrate in acetonitrile to give a
concentration of 1 × 103 to 2 × 103 ppm. An inter-
nal standard was then added, the amount of which
was adjusted to give the desired peak area ratio of
substrate to standard (2.5:1). The solvent and stan-
dard were selected to be stable under the conditions
of pyrolysis, and because they do not interact or react
with either substrate or product. The internal standard
used in the present study was benzene for compounds
1–5 and 14, and 1,3-dichlorobenzene for substrates
6–13. Each mixture was filtered before use to ensure
a homogeneous solution. Care was exercised when us-
ing benzene, and this compound could be replaced by
toluene.
Synthesis of N,Nꢀ-diphenylpropanediamide (14)
[25] from the reaction of equimolar amounts of
dimethyl malonate with aniline as described in the lit-
erature, for 10 min at 180◦C. The solid recovered was
recrystallized from dilute ethanol.
The ratio of the amount of substrate with respect
to the internal standard was calculated from the ra-
tio 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: An aliquot
part (0.2 mL) of each solution containing the substrate
and the internal standard was pipetted into the pyrol-
ysis tube, which was then cooled in liquid nitrogen
and sealed at reduced pressure (0.28 mbar). The tube
was then placed in the pyrolyzer for 6 min under non-
thermal conditions (ambient temperature). A sample
was then analyzed using HPLC with UV/VIS detector
at wavelength, λ = 250–260 nm, to calculate the stan-
dardization value (Ao). Several HPLC measurements
were obtained with an accuracy ≥2%. The temperature
of the pyrolysis block was then raised until ca. 10% py-
rolysis of the substrate was deemed to occur over 600-s
interval except substrate 14 for which the interval was
540 s; the HPLC measurements were carried out as
above. This process was repeated after each ca. 10◦C
rise in the reaction temperature until >95% reaction
was achieved. The relative ratios of the sample and the
internal standard (A) at each reaction temperature were
calculated for a minimum of three kinetic runs made
at each of these temperatures that were in agreement
to within 2% in order to ensure reproducible values
of (A). Treatment of the kinetic data has been detailed
elsewhere [15,19,20].
N-Phenyl-3-oxobutanamide, acetoacetanilide (1).
1
mp 85◦C (lit. [21] 83–86◦C); H NMR δ (CDCl3):
2.31 (3H, s, CH3), 3.57 (2H, s, CH2), 7.09–7.58 (5H,
n, ArH), 9.20 (1H, b, NH); MS (EI) M+, m/z = 177;
C10H11NO2 requires: C, 67.78; H, 6.25; N, 7.90%.
Found: C, 67.28; H, 6.30; N, 7.67%.
N-(P-Chlorophenyl)-3-oxobutanamide
(2). mp
128◦C (lit. [25] 132◦C); H NMR δ (CDCl3): 2.28
(3H, s, CH3), 3.55 (2H, s, CH2), 7.18–7.40 (4H,
m, ArH), 9.20 (1H, b, NH); MS (EI) M+/M+ + 2,
m/z = 211/213; C10H10NO2Cl requires: C, 56.74; H,
4.76; N, 6.62%. Found: C, 57.32; H, 4.67; N, 6.52%.
1
N-(P-Methylphenyl)-3-oxobutanamide (3). mp 95◦C
(lit. [26] 95◦C); 1H NMR δ (CDCl3): 2.29 (3H, s, CH3),
2.56 (3H, s, CH3), 3.55 (2H, s, CH2), 7.10–7.27 (4H,
m, ArH), 9.20 (1H, b, NH); MS (EI) M+, m/z = 191;
C11H13NO2 requires: C, 69.09; H, 6.85; N, 7.32%.
Found: C, 69.08; H, 6.80; N, 7.10%.
N-(P-Methoxyphenyl)-3-oxobutanamide
(4). mp
118◦C (lit. [26] 117◦C); H NMR δ (CDCl3): 2.32
(3H, s, CH3), 3.56 (2H, s, CH2), 3.78 (3H, s, OCH3),
6.95–7.38 (4H, m, ArH); 9.20 (1H, b, NH); MS (EI)
M+, m/z = 207; C11H13NO3 requires: C, 63.76; H,
6.32; N, 6.44%. Found: C, 63.22; H, 6.47; N, 6.44%.
1
International Journal of Chemical Kinetics DOI 10.1002/kin

KINETICS AND MECHANISM OF GAS-PHASE PYROLYSIS OF N-ARYL-3-OXOBUTANAMIDE KETOANILIDES
85
2-Phenylhydrazono-acetoacetanilide (5). mp 108–
109◦C (lit. [23,24] 108–110◦C); 1H NMR δ (CDCl3):
2.57 (3H, s, CH3), 7.12–7.68 (10H, m, ArH), 11.50
(1H, b, NH), 14.80 (1H, b, NH); MS (EI) M+,
m/z = 281; C16H15N3O2 requires: C, 68.32; H, 5.37;
N, 14.94%. Found: C, 67.90; H, 5.36; N, 15.10%.
N-Phenyl-3-oxo-3-phenylpropanamide
(13). mp
91◦C, 1H NMR δ (CDCl3): 3.58 (2H, s, CH2),
7.06–7.99 (10H, m, ArH), 9.26 (1H, s, NH); MS(EI)
M+, m/z = 239; C15H13NO2 requires: C, 75.3; H,
5.47, N, 5.85%. Found: C, 74.85; H, 5.61; N, 6.12%.
N,Nꢀ-Diphenylpropanediamide (14). mp 226◦C (lit.
[27] 220, 225◦C). 1H NMR δ (CDCl3): 3.58 (2H,
s, CH2), 7.17 (2H, t, J = 7.8), 7.37 (4H, t, J = 8.0),
7.58 (4H, d, J = 7.9), 8.89 (2H, s, NH); MS (EI) M+,
m/z = 254; C15H14N2O2 requires: C, 75.3; H, 5.47, N,
5.85%. Found: C, 74.85; H, 5.61; N, 6.12%.
N-(P-Chlorophenyl)-2-phenylhyrazono-3-oxobutan-
amide (6). mp 127◦C; 1H NMR δ (CDCl3): 2.58
(3H, s, CH3), 7.17–7.64 (9H, m, ArH), 11.50 (1H,
b, NH); 14.80 (1H, b, NH); MS (EI) M+/M+ + 2,
m/z = 315/317; C16H14N3O2Cl requires: C, 60.80;
H, 4.40; N, 13.30%. Found: C, 60.05; H, 4.20; N,
13.54%.
RESULTS AND DISCUSSION
Kinetic Analysis
N-(P-Methylphenyl)-2-phenylhyrazono-3-oxobutan-
amide (7). mp 116–117◦C; 1H NMR δ (CDCl3): 2.31
(3H, s, CH3), 2.58 (3H, s, CH3), 7.10–7.38 (9H, m,
ArH), 11.50 (1H, b, NH); 14.80 (1H, b, NH); MS
(EI) M+, m/z = 295; C17H17N3O2 requires: C, 69.15;
H, 5.76; N, 14.24%. Found: C, 69.58; H, 5.88; N,
14.60%.
The kinetic data on the pyrolysis of compounds (1–14)
are summarized in Table I. The reactions followed
first-order kinetics. Each rate constant at a given
temperature represents an average of at least three
measurements in agreement to within 2% rate
spread. To ensure reliable kinetic results, the pyrolysis
of each substrate was followed over 59 12 K tem-
perature range and 94%–98% reaction [6–8,12–16].
The Arrhenius log A(s−1) and activation energy (Ea,
kJ mol−1), and the rate constants (k, s−1) at 450
K for the reactions of the compounds under study
are recorded in Table II. The Arrhenius plots were
strictly linear over >95% reaction with correlation
coefficients in the order of 0.99 0.01. Typical plots
are shown in Figure 1 for ketoanilide substrate 1 and its
phenylhydrazono derivative (5). The coefficients for
these two correlations are 0.99 and 1.00, respectively.
P-(P-Methoxyphenyl)-2-phenylhyrazono-3-oxobuta-
namide (8). mp 129–130◦C; lit. [24] 125–126◦C;
1H NMR δ (CDCl3): 2.56 (3H, s, CH3), 3.78 (3H,
s, OCH3), 6.83–7.58 (9H, m, ArH), 11.50 (1H, b,
NH); 14.80 (1H, b, NH); MS (EI) M+, m/z = 311;
C17H17N3O3 requires: C, 65.59; H, 5.46; N, 13.50%.
Found: C, 65.30; H, 5.47; N, 12.70%.
2-(P-Chlorophenylhyrazono)acetoaceanilide (9). mp
1
143◦C (lit. [24] 142–143◦C); H NMR δ (CDCl3):
2.51 (3H, s, CH3), 7.32–7.38 (9H, m, ArH), 11.50
(1H, b, NH); 14.80 (1H, b, NH); MS (EI) M+/M+
+
To facilitate comparison, the rate constants (k, s−1
)
2, m/z = 315/317; C16H14N3O2 requires: C, 60.80; H,
of thermolysis at 450 K of compounds (1–14) are
compiled in Figure 2. The figure also includes the
rate constants at 600 K reported earlier for six related
diketone and cyano analogues (15–20) [2,16]. The
reactions of all these substrates obeyed a first-order
rate equation, and the values of their Arrhenius log
A(s−1) and Ea(kJ mol−1) parameters are in the range
expected for unimolecular polar thermal gas-phase
elimination reactions [6–8,12–16]. Reaction rates
were followed by monitoring the disappearance of
substrates during reaction. The rate coefficients at
T = 450 K were calculated using the kinetic relation:
log k = log A − Ea/4.574T ; log A and Ea being the
Arrhenius parameters obtained for the substrates. The
limits of error in Table II represent the correlation
statistical values. The rate coefficients were computed
at T = 450 K for two valid reasons: (i) this temper-
ature lies well within the range (374–546 K) over which
4.40; N, 13.30%. Found: C, 60.81; H, 4.33; N, 13.34%.
2-(P-Methylphenylhyrazono)acetoaceanilide (10).
mp 128◦C (lit. [24] 125–127◦C); 1H NMR δ (CDCl3):
2.34 (3H, s, CH3), 2.58 (3H, s, CH3); 7.32–7.38 (9H,
m, ArH), 11.50 (1H, b, NH); 14.80 (1H, b, NH); MS
(EI) M+, m/z = 295; C17H17N3O2 requires: C, 69.15;
H, 5.76; N, 14.24%. Found: C, 69.11; H, 5.81; N,
14.40%.
2-(P-Methoxyphenylhyrazono)acetoaceanilide (11).
mp 130◦C (lit. [24] 127–129◦C); 1H NMR δ (CDCl3):
2.49 (3H, s, CH3), 3.78 (3H, s, OCH3); 6.83–7.58 (9H,
m, ArH), 11.50 (1H, b, NH); 14.80 (1H, b, NH); MS
(EI) M+, m/z = 311; C17H17N3O3 requires: C, 65.59;
H, 5.76; N, 14.24%. Found: C, 69.11; H, 5.81; N,
14.40%.
International Journal of Chemical Kinetics DOI 10.1002/kin

86
MALHAS, AL-AWADI, AND EL-DUSOUQUI
Table I Kinetic Data for Gas-Phase Pyrolysis of
Compounds 1–14
Table I Kinetic Data for Gas-Phase Pyrolysis of
Compounds 1–14 (Continued)
Compound
T (K)
103 k (s−1
)
Compound
T (K)
103 k (s−1
)
1
374.2
396.8
416.2
426.0
436.0
441.6
445.6
387.2
399.3
409.1
422.6
428.6
432.6
438.7
399.9
408.9
414.3
423.2
430.4
437.1
445.6
399.5
410.5
420.0
426.2
433.4
450.4
453.4
498.2
518.4
528.3
533.6
540.8
545.6
489.2
502.1
503.8
514.5
524.2
533.6
545.0
493.2
502.0
511.4
523.4
533.4
542.9
497.2
506.5
516.1
525.7
536.3
544.8
0.030
9
494.0
503.5
511.8
521.9
531.3
542.3
494.3
502.0
511.6
521.3
531.2
538.3
484.7
494.1
504.8
515.1
523.7
534.1
541.7
413.2
423.2
434.7
440.0
443.2
448.2
458.3
408.3
418.0
425.7
435.6
444.7
454.3
466.6
484.9
488.3
498.3
501.3
508.1
517.7
0.252
0.158
0.647
1.43
3.78
4.32
0.482
0.883
1.99
4.06
7.88
0.175
0.346
0.775
1.33
2.78
4.39
0.187
0.361
0.696
1.40
2.80
5.20
6.75
10
11
2
3
4
0.030
0.298
0.602
1.22
1.41
3.40
8.72
0.243
0.321
0.515
0.873
1.41
9.43
4.87
7.07
12
0.099
0.270
0.704
1.00
1.29
1.92
3.68
0.662
1.37
2.29
4.43
0.086
0.193
0.404
0.702
1.18
3.14
4.85
0.215
0.952
1.78
2.58
4.38
6.15
0.074
0.263
0.391
0.541
1.27
2.46
5.07
0.133
0.192
0.388
1.26
2.46
4.30
0.171
0.336
0.710
1.45
13
14
5
6
7.90
9.78
0.086
0.309
0.416
0.787
0.891
1.31
2.57
the present reactions were studied and (ii) the rates
at this temperature would facilitate direct comparisons
with data on rates from earlier studies, should the need
arise.
7
8
Reaction Products and Mechanism
To ensure complete substrate pyrolysis, reactions for
product analysis were carried out at temperatures ex-
ceeding those required for >98% reaction as per ki-
netic measurements, namely, a range of ca. 475–600 K.
Absence of substrates from product mixtures was
further confirmed by inspection of data on reaction
2.95
5.19
Continued
International Journal of Chemical Kinetics DOI 10.1002/kin

KINETICS AND MECHANISM OF GAS-PHASE PYROLYSIS OF N-ARYL-3-OXOBUTANAMIDE KETOANILIDES
87
Table II Arrhenius Log A (s−1), Energy of Activation
(Ea, kJ mol−1), and Rate Constants (k, s−1) at 450 K for
Gas-Phase Pyrolysis of Compounds 1–14
transfer from the (N H) moiety to a protophilic (C O)
center whereas the four-center TS requires fission of
a relatively stronger (C C) bond. Moreover, theoreti-
cal studies using ab initio calculations have supported
the cyclic six-membered TS in numerous thermal gas-
phase elimination reactions, and an analogous TS has
also been proposed to explain the results from the
gas-phase thermolysis of pentane-2,4-dione (15), its
3-phenylhydrazono derivative (16), and the cyano ana-
logues (17–20) (Fig. 2) [2,8,16].
Accordingly, the kinetic results reported here
are analyzed and discussed using the proposed re-
action mechanism. The assessment of structure–
reactivity correlations and substituent effects for
(1–14) and related compounds is consistent with this
mechanism.
Compound log A (s−1
)
E (kJ mol−1
)
k s−1 at 450 K
a
1
2
3
4
5
6
7
8
10.22 0.39 106.1 2.93
8.13 × 10−3
16.2 × 10−3
14.0 1.4
136.1 1.35
9.97 0.01 105.0 0.012 6.02 × 10−3
10.39 0.24 110.4 1.92
12.97 0.16 158.7 1.63
13.19 0.57 161.3 5.44
13.49 0.82 164.7 8.68
13.28 0.09 162.3 0.92
13.59 0.34 162.7 3.14
13.15 0.36 159.6 3.51
12.30 0.20 148.9 2.22
11.76 0.05 124.3 3.04
9.91 0.56 102.2 4.56
10.69 0.19 131.7 1.80
3.80 × 10−3
3.50 × 10−6
2.85 × 10−6
2.36 × 10−6
2.75 × 10−6
5.13 × 10−6
4.28 × 10−6
10.5 × 10−6
2.14 × 10−3
11.2 × 10−3
2.57 × 10−5
9
10
11
12
13
14
Hammett and Structure–Reactivity
Correlations
A plot of log kG/kH of compounds 1–4 (0.00, 0.30,
−0.13, −0.33) against the Hammett σ values of the cor-
responding substituent constants (0.00, 0.21, −0.16,
−0.29) shows a linear Hammett correlation and gives
a reaction constant, ρ = 1.22 0.03 (Fig. 3) [15c,d].
This correlation lends support to the proposed mecha-
nism, and demonstrates the importance of N H bond
breaking (bond (i), Schemes 1 and 2) to the overall
molecular reactivity of the ketoanilides under study, as
well as the effect substituents have on charge develop-
ment on the amide (NH) hydrogen.
A positive Hammett reaction constant with a magni-
tude of ρ = 1.22 is indicative of considerable negative
charge development on the amide (N) atom concomi-
tant with the departure of the (NH) proton to the pro-
tophilic carbonyl (C O) moiety. Aryl groups attached
to the amide (N) would neutralize the negative charge
and consequently stabilize the TS and hence increase
rates of reaction when the aryl groups have electron-
withdrawing substituents, whereas aryl groups with
electron-donating substituents would be expected to
retard the rate of reaction relative to the phenyl group.
These structure–reactivity correlations are borne out by
the quantitative Hammett analysis of the kinetic data
from the present ketoamides. We have previously used
Hammett correlations in the analysis of the kinetics
and mechanism of several thermal gas-phase elimina-
tion reactions, and have also provided novel gas-phase
Hammett replacement substituent constants of furyl,
thienyl, and pyridyl systems [15a–c].
products. The pyrolysates were analyzed using GC-
MS and HNMR, and typical representative results are
shown in Table III. The pyrolysate from each sub-
strate consisted of two fragments only: (i) a phenyl or
aryl isocyanate fragment and (ii) acetone, acetophe-
none, PhNHN CHCOCH3, ArNHN CHCOCH3, or
acetanilide fragment. It is important to note that no
ketene compounds were detected among the prod-
ucts of pyrolysis. These results could be fully ex-
plained on the basis of a reaction mechanism with a
cyclic six-membered TS (Scheme 2). The other plau-
sible pathway involves a four-membered TS, which
would also account for the observed reaction products
(Scheme 2). However, the former TS is thermodynam-
ically more stable, and it involves a facile hydrogen
−1
Substrate 1
Substrate 5
−2
−3
−4
−5
−6
Intercept : 12.97
Intercept : 10.22
Slope
r ²
: −8.29
: 0.999
Slope
: −5.55
r ²
: 0.990
1.6
1.8
2.0
2.2
2.4
2.6
2.8
Furthermore, the effect of bond (i) on molecular re-
activity also provides an explanation for the following:
(a) the large (1.8 × 106 fold) difference in the rate con-
stants of the reaction of compound 15 compared with
1000/T
Figure 1 Arhenius plots of log k vs. 1000/T for substrates
1 and 5.
International Journal of Chemical Kinetics DOI 10.1002/kin

88
MALHAS, AL-AWADI, AND EL-DUSOUQUI
G
Cpd
G
:
:
1
H
2
3
4
O
N
Cl CH3 OCH3
103 k(s−1) : 8.13 16.2 6.02 3.80
H
G
O
Cpd
G
: 5
6
7
8
O
N
: H Cl CH3 OCH3
106
k(s−1) : 3.50 2.85 2.36 2.75
NHN
H
O
Ph
H
Cpd
G
106k(s−1
:
:
9
10
11
O
Cl CH3 OCH3
N
O
)
: 5.13 4.28 10.5
G
NHN
O
Ph
H
H
Ph
H
O
O
N
O
N
N
O
H
O
Ph
N
Ph
H
14
12
13
103k(s−1) : 2.14
11.2
0.0257
O
Ph
H
O
O
N
H
O
PhNHN
H
O
CN
15
16
17
–6
1.35 × 10–3
2.80 × 10–4
k (s−1
)
)
: 5.25 × 10
O
O
O
PhNHN
p-O2NC6H4NHN
p-CH3OC6H4NHN
H
H
H
CN
CN
CN
18
: 1.45 × 10–2
19
20
2.51 × 10–1
1.15 × 10–2
k (s−1
Figure 2 Rate constants at 450 K of compounds 1–14 and at 600 K of compounds 15–20.
substrate 1 (k = 9.46 s−1 at 600 K), which correlates
with C H bond cleavage in 15 compared with a more
facile hydrogen exchange in 1; (b) the higher reactiv-
ity (ca. 3.8 fold) of 1 over 12 due to the stabilizing
substituent effect of the phenyl group on partial charge
development at the incipient amide proton of 12. Be-
sides, the effect of substituents on the protophilicity of
bond ((iii) of Schemes 1 and 2), and hence on molecu-
lar reactivity, is reflected in the rates of reaction of the
1/13 substrate pair.
tuted 2-arylhydrazono ketoanilides (5–8) are less reac-
tive than the unsubstituted analogues (1–4) by factors
≥1.4 × 103. Unsubstituted pentane-2,4-dione (15) is,
on the other hand, ca. 2.6 × 102 times less reactive than
its phenylhydrazone derivative (16). Analysis of the ef-
fect of the phenylhydrazono group on the kinetic and
mechanistic behavior of these two systems provides a
novel example of structure–reactivity correlation stud-
ies. Structurally, the two carbonyl (C O) functions of
the diketones (15,16) are equivalent, and hence when
one function is bound in an interaction with the phenyl-
hydrazono group (16), the other is still available to
participate in the thermal elimination (pyrolysis) path-
way (Schemes 1 and 2) responsible for both reaction
The influence of the arylhydrazono substituent
on the reactivity of the present ketoanilides and of
pentane-2,4-dione derivatives is quite significant in
both magnitude and direction (Fig. 2). The substi-
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KINETICS AND MECHANISM OF GAS-PHASE PYROLYSIS OF N-ARYL-3-OXOBUTANAMIDE KETOANILIDES
89
0.4
Table III GC-MS and H NMR of Pyrolysate Fragments
M+ (m/z)
δ/ppm (CDCl3)
0.3
Fragment
ρ = 1.22
0.2
0.1
PhN C O
PhCOCH3
119
120
7.05–7.49 (m, ArH)
7.20–8.05 (m, ArH)
2.50 (3H, s, CH3)
6.95–7.18 (m, ArH)
2.10 (3H, s, ArH)
6.65–7.50 (m, ArH)
3.76 (3H, s, OCH3)
6.95–7.18 (m, ArH)
0.0
p-CH3C6H4N C O
p-CH3C6H4N C O
p-ClC6H4N C O
PhNHN CHCOCH3
133
149
−0.1
−0.2
−0.3
−0.4
153
155
162
7.18–7.35 (m, ArH)
25.7–2.60 (3H, s, CH3)
11.50 (1H, s, NH)
−0.4
−0.3
−0.2
−0.1
0.0
0.1
0.2
0.3
σ
p-CH3C6H4NHN
176
135
7.10–7.60 (m, ArH)
Figure 3 Hammett correlation of log kG/kH for compounds
1–4.
CHCOCH3
2.05 (3H, s, CH3)
11.45 (1H, s, NH)
7.13–7.60 (m, ArH)
2.55 (3H, s, CH3)
10.15 (1H, s, NH)
PhNHCOCH3
(16). Furthermore, the electron-withdrawing p-NO2
group increased the reactivity of compound 19 over 18
through an increase in the positive charge of the hy-
drazono (NH) hydrogen, while the electron-donating
p-OCH3 group produced the expected opposite effect
(20). The higher reactivity of the cyanoketones 18–
20 over the diketone 16 is to be expected since any
kinetically adverse effect by the phenylhydrazono sub-
stituent would be less pronounced on the linear (CN)
than on the angular carbonyl (C O) group (Scheme 4).
In absence of the phenylhydrazono substituent, how-
ever, this structural difference makes the cyanoanilide
17 less reactive than the analogous ketoanilide 1, as the
(CN) group would be less effective in the development
of the TS leading to pyrolysis than the (C O) group
(Scheme 2).
By contrast, the two (C O) moieties of the ke-
toanilides 1–11 are structurally nonequivalent. The
ketone (C O) group constitutes the protophilic func-
tion in the elimination (pyrolysis) pathway (bond (iii),
Schemes 1 and 2). Hydrogen transfer from the amide
(NH) function tothis protophilic(C O) groupis shown
above by Hammett and structure–reactivity correla-
tions to be an important step in pyrolysis affecting
rate and determining reaction product. An interaction
kinetics (observed rate) and reaction products (molecu-
lar fragmentation). In addition, the engagement of one
of the two equivalent (C O) functions by the hydra-
zono group assists in the development of partial pos-
itive charge on the hydrogen being transferred to the
other still available (C O) function further affecting
pyrolysis (Scheme 3). The net result is an enhancement
of the rate of pyrolysis of the diketone through the as-
sistance of the phenylhydrazono group without inter-
ference with the elimination (pyrolysis) route. It has
earlier been suggested that the hydrazono substituent
increases reactivity by increasing bond polarity (bond
(ii), Schemes 1 and 2) and protophilicity (bond (iii))
[16].
The rates of reaction of the cyano ketones (18–
20) show appreciable rate-enhancement also due to the
phenylhydrazono group (Fig. 2), and all three ketones
are more reactive than the phenylhydrazono diketone
O
Ar
(i)
O
Ar
C
C
N
O
C
N
(ii)
GC
H
GC
H
H
N
O
COR
(b)
(iii)
R
PhN
H
heat
heat
O
O = C = NAr + GCH COR
G : H2 ; ArNHN= R: CH3; Ph; NHPh
(a)
Scheme 3 Two equivalent (C O) functions: one (a) en-
gaged in (H) transfer leading to elimination and the other (b)
promotes H-bond donor acidity.
Scheme 2
Plausible reaction pathways for gas-phase
pyrolysis.
International Journal of Chemical Kinetics DOI 10.1002/kin

90
MALHAS, AL-AWADI, AND EL-DUSOUQUI
pathway and the partioning of the (N) lone pair by the
phenyl group. The observed rate-reduction factor also
represents a lower limit, since the anilide (PhNH) sub-
stituent is expected to enhance the protophilicity of its
(C O) group through the (N) lone pair of electrons.
Ar
H
O
N
N
H
ArN
O
Scheme 4 Competitive process adversely affecting rate of
thermal elimination without resultant fragmentation.
CONCLUSION
The kinetics, reaction product, and Hammett ρ/σ cor-
relation analysis are reported for the unimolecular gas-
phase pyrolysis of seven ketoamides and seven of their
arylhydrazono compounds, and the results are ade-
quately rationalized on the basis of a mechanism in-
volving a concerted six-membered TS. The first-order
rate constants of the present ketoamides are compared
with those reported for the analogous 1,3-diketones,
cyanoketones and their arylhydrazono derivatives. The
arylhydrazono substituent displayed a novel structural
effect in that it increased (>250-fold) the reactivity
of the diketones by enhancing the H-donor acidity of
the incipient proton in the TS of the elimination pro-
cess. However, the arylhydrazono group, on the other
hand, retarded (>1000-fold) the reactivity of the ke-
toamides by providing a competitive intramolecular
proton transfer cyclization process.
between this ketone (C O) group and the arylhydra-
zono (NH) hydrogen in the substituted ketoanilide
compounds would result in a competing process ad-
versely affecting the rate of pyrolysis. This competi-
tive process is shown in Scheme 4 (a six-membered
intramolecular cyclization process), and would as such
lead to rate reduction but would not, however, produce
fragmentation along this route. On the basis of formal
bond dissociation energies, the TS development, ac-
cording to Scheme 4, is energetically more favorable
than for the TS of Scheme 2. However, a more rigorous
approach would be a theoretical study to calculate and
compare the thermal activation barriers of the asyn-
chronous cyclic six-membered TSs of the two compet-
ing processes. Rate reduction could in principle also be
ascribed to H-bond effects [17,18]. The magnitude of
the experimentally observed rate-reduction factor for
the ketoanilide compounds (ca. 1.4 × 103 −5.7 × 103)
represents only a lower limit since the adverse compet-
itive process (Scheme 4) comes partly at the expense
of the rate-enhancing effect of the hydrazono group
discussed above (Scheme 3).
One of the authors (R.N.M.) thanks the College of Graduate
Studies, Kuwait University, for an M.Sc. candidacy. Grants
from ANALAB and SAF are gratefully acknowledged.
Evidence in support of the adverse and of the rate-
enhancing effects of the phenylhydrazono group with
regard to the reactivity of ketoanilides is provided by
the ratios of the rates of reaction of compounds 5, 9,
10, and 11. Compounds 10 and 11 are both more re-
active than 5, because of the electron-donating methyl
and methoxyl groups that retard positive charge de-
velopment on the hydrazono (NH) hydrogen and thus
minimize its adverse effect on substrate reactivity. The
higher rate of pyrolysis of 9 compared to 5 would be
the result of greater differential assistance by the hy-
drazono (NH) hydrogen in promoting positive charge
development on the incipient amide (NH) hydrogen
with which it is hyperconjugated through the amide
(C=O) moiety (Scheme 3).
A feasible 4-centered competitive pathway, anal-
ogous to the 6-centered intramolecular cycliza-
tion structure (Scheme 4), is shown for N,Nꢀ-
diphenylpropanediamide (14) in Figure 2. The fact that
this substrate is ca. 316 times (633 times, on statisti-
cal basis) less reactive than acetoacetanilide 1 could
be attributed to the adverse effect of the competing
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