The kinetics and mechanism of cyclodimerization of alkylthiopropenals

Article abstract of DOI:10.1023/A:1009507522009

The kinetics of 2-alkylthiopropenals cyclodimerization was studied in the temperature range from -7 to +42 °C in heptane and at 20 °C in various solvents. The rate constants for cyclodimerization of 2-alkylthiopropenals are four orders of magnitude higher than those for dimerization of the oxygen-containing analogs, 2-alkoxypropenals, and are independent of the solvent polarity and substituent steric constant. The activation parameters for 2-butylthiopropenal cyclodimerization were estimated. The distribution of electron density in the 2-methoxy-and 2-methylthiopropenals molecules was calculated by the ab initio method. From comparison of the HOMO and LUMO energies for these aldehydes it was concluded that the ratio between the cyclodimerization rates for 2-alkylthio-, 2-ethoxypropenals, and propenal is determined by the HOMO-LUMO gap.

Full text of DOI:10.1023/A:1009507522009

Russian Chemical Bulletin, International Edition, Vol. 49, No. 12, December, 2000
1977
The kinetics and mechanism of cyclodimerization of alkylthiopropenals
«
N. A. Keiko, L. G. Stepanova, G. I. Sarapulova, A. V. Vashchenko, L. I. Larina,
E. A. Funtikova, and M. G. Voronkov
Irkutsk Institute of Chemistry, Siberian Branch of the Russian Academy of Sciences,
1 ul. Favorskogo, 664033 Irkutsk, Russian Federation.
Fax: +7 (395 2) 39 6046. E-mail: keiko@irioch.irk.ru
The kinetics of 2-alkylthiopropenals cyclodimerization was studied in the temperature
range from –7 to +42 °C in heptane and at 20 °C in various solvents. The rate constants for
cyclodimerization of 2-alkylthiopropenals are four orders of magnitude higher than those for
dimerization of the oxygen-containing analogs, 2-alkoxypropenals, and are independent of the
solvent polarity and substituent steric constant. The activation parameters for 2-butyl-
thiopropenal cyclodimerization were estimated. The distribution of electron density in the
2
-methoxy- and 2-methylthiopropenals molecules was calculated by the ab initio method.
From comparison of the HOMO and LUMO energies for these aldehydes it was concluded
that the ratio between the cyclodimerization rates for 2-alkylthio-, 2-ethoxypropenals, and
propenal is determined by the HOMO—LUMO gap.
Key words: 2-alkylthiopropenals, Diels—Alder reaction, kinetics, reaction mechanism,
2
,5-dialkylthio-3,4-dihydro-2H-pyran-2-carbaldehyde, IR spectroscopy, ab initio calculations.
Many naturally occurring molecules contain the pyran
ring and its hydrogenated forms.1,2 The Diels—Alder
reaction, in which 1-oxa-1,3-butadienes are the diene
components, is widely used for the synthesis of these
heterocyclic compounds.1 The interaction between
α,β-unsaturated aldehydes or ketones and electron-
enriched alkenes such as enol ethers or thioethers is a
convenient method for the synthesis of substituted 3,4-di-
hydro-2Í-pyrans,3,4 and some of them are bio-active
compounds and medicines.5—7
Results and Discussion
The rate constant of reaction (1) was monitored by
IR spectroscopy either by a decrease in the absorbance of
the C=O or Ñ=Ñ absorption bands of a monomer or by
an increase in the absorbance of these bands in the dimer
molecule. The solvents used exclude specific interactions.
The frequencies of the absorption bands in the solvents
are presented in Table 1. It is seen that the nature of alkyl
substituents and solvents have no effect on conjugation in
the molecules of the monomer or dimer.
Earlier8 we have shown that 2-alkylthiopropenals
dimerize easily according to the Diels—Alder scheme,
transforming into 2,5-dialkylthio-3,4-dihydro-2Í-pyran-
The kinetics of cyclodimerization obeys a second
order equation. The rate constant was calculated by the
formula
2
-carbaldehydes. In our study of the kinetics of
cyclodimerization of acrolein and its α-substituted
derivatives, we have found that the dimerization of 2-alkyl-
k = x/[ta(a – x)],
where à is the initial molar concentration of monomer
1, and õ is the molar concentration of the monomer
transformed to dimer 2 at time t.
thiopropenals is too fast and inaccessible for kinetic
measurements.9 However, when the retrodiene decay of
2
,5-dialkylthio-3,4-dihydro-2Í-pyran-2-carbaldehydes
was used, binary mixtures of a monomer and cyclic dimer
containing from 25 to 80% 2-alkylthiopropenal were
obtained.10 The rate constants for cyclodimerization of
Table 1. Absorption frequencies (ν/cm–1) for monomers 1 and
dimers 2 in various solvents
2
-alkylthiopropenals in CDCl have been determined in a
3
R
Solvent
ν(Ñ=Ñ)
ν(Ñ=Î)
1
11
Í NMR study of the composition of these mixtures.
This work continues our studies of the kinetics and
mechanism of reaction (1) and also presents the results
of quantum-mechanical calculations of the structures of
the starting reagents.
1
2
1
2
Ea nt He ept
Pr
Bu
1585
Heptane
MeÑN
Acetone-d6
THF
1626
1687 1728
1628
1580
1582
1583
1582
1584
1584
1582
1580
1690 1728
1685 1728
1687 1730
1683 1728
1685 1730
1687 1732
1682 1730
1692 1725
1624
1628
1626
1626
1628
1626
1626
RS
RS
+
SR
(1)
ÑDCl3
O
CHO
Heptane
Microlayer
Heptane
O
RS
CHO
1
2
C H
6
13
R = Et, Pr, Bu, C H
6
13
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 12, pp. 2009—2013, December, 2000.
066-5285/00/4912-1977 $25.00 © 2000 Plenum Publishing Corporation
1

1
978
Russ.Chem.Bull., Int.Ed., Vol. 49, No. 12, December, 2000
Keiko et al.
Table 2. Rate constants of 2-butylthiopropenal cyclodimerization
in various solvents at different temperatures
It is typical of reactions proceeding through a polar
transition state to be accelerated with an increase in the
dielectric constant of the medium.14 Variation in the
solvent polarity did not change significantly the cyclo-
dimerization rate for 2-butylthioacrolein (see Table 2).
Hence, the transition state of reaction (1) is nonpolar.
Examination of the data of Table 3 on the distribution
of the electron density in the aldehydes studied indicates
that the highest negative charge occurs, as a rule, at the
Cβ atom of 2-methoxy- and 2-methylthiopropenals in
their ground state. The gradient along the Ñ=Ñ bond in
the trans-form is considerably greater than that in the
cis-form. The charge on the Cβ atom in 2-methoxy-
propenal is nearly two times higher than that in 2-methyl-
Solvent
ε
T/°C
k•104
/L mol–1 s–1
(
20 °C)
Heptane
1.92
42
3.81±1.2
3
2
–
20
20
20
20
2
0
7
2.57±1.39
1.21±0.31
0.21±0.02
0.99±0.81
1.09±1.14
0.49±0.15
0.35±0.05
THF
7.5
1
,2-Dichloroethane 10.1
Acetone-d6
MeCN
20.7
36.0
thiopropenal.
The rate constants of cyclodimerization of 2-butyl-
thiopropenals at various temperatures and in different
solvents are shown in Table 2.
This does not contradict the 1H and 13Ñ NMR
spectral data for 2-ethoxypropenal and 2-butylthio-
propenal.15 The spectra showed that the C atom in both
β
The temperature dependence of the rate constant
for 2-butylthiopropenal cyclodimerization obeys the
Arrhenius equation (Fig. 1). On this basis we found the
molecules is more screened than the Cα atom and the
β-atom in the oxygen analog is more screened than that
in the sulfur analog (see Experimental). It is highly
improbable that similarly charged fragments (for example,
the Cβ atoms) of two molecules approached each other
in the polar transition state.
It is known1,13,16 that the reaction rate depends not
only on the electron nature of substituents in a diene
molecule but also on their effect on the conformational
equilibrium, and the reaction rates for open-chain dienes
depends on the content of the cis-conformer. As the
calculation of the overall energy of the conformers of
aldehydes showed (see Table 3), the S-trans-form is
more favorable for the ground states of oxygen- and
sulfur-substituted propenals.* The difference between
the energies of the trans- and cis-conformers is
–
1
effective activation energy E = 39.7±7.5 kJ mol and
a
Arrhenius preexponential factor À, logA = 3.2. For
cyclodimerization of the oxygen analog of 2-butylthio-
propenal (2-ethoxypropenal) E = 86.0 kJ mol–1 and
a
9
logA = 7.1 in cyclohexane. Then, the rate constant for
cyclodimerization of 2-ethoxypropenal at 20 °C is
–
9
–1 –1
6
.3•10
L mol
s
. Thus, 2-alkylthioacroleins
cyclodimerize more than four orders of magnitude faster
than their oxygen analogs.
≠
–1
The enthalpy of activation ∆Í = 37.2±7.5 kJ mol
≠
and the entropy of activation ∆S = –203.9±59.0
J K mol for 2-butylthiopropenal cyclodimerization
–
1
–1
at 20 °C were calculated from the values of Å and logA.
a
The high negative effective entropy of activation
found is typical of the reactions of diene synthesis
proceeding through a cyclic transition state.12,13
To verify the possibility of the participation of free
radicals in the reaction, 2-butylthiopropenal cyclodimeri-
zation was carried out in the dark in the presence of
hydroquinone and in the light in the absense of
hydroquinone. In both cases, the reaction rates turned
out the same.
.5 kcal mol–1 (∆E = 0.00394 Hartree) in the first case
compounds 3à and 3b, respectively) and 1.9 kcal mol
∆E = 0.003008 Hartree) in the second case (compounds
2
(
(
–1
4
à and 4b, respectively). This means that the trans-form
of the molecules of both oxygen- and sulfur-substituted
dienes has to isomerize into the cis-form prior to
participation in diene synthesis. The barrier for transition
from the S-trans- to S-cis-form was estimated from the
potential energy of internal rotation of the aldehyde
group about the σ-bond. The energy barrier for this
–
1
transition is 9.0 kcal mol
7
for 2-alkoxypropenal and
5
+ lg(k/L mol–1 s–1
)
.5 kcal mol–1 for its thio-analog. Hence, the relative
easiness of the trans- to cis-isomerization of 2-alkylthio-
-propenals may account for the higher rates of their
dimerization as compared to the oxygen analogs.
As is known, bulky substituents in position 3 often
favor the formation of the cis-like diene conformation
and thereby such dienes are more reactive. However, a
comparison of the rate constants for cyclodimerization
of various 2-alkylthiopropenals shows that the bulk of a
1
1
0
0
.6
.2
.8
.4
2
*
The orthogonal form of 2-methoxypropenal, in which the
T –1•10 /K
3
–1
3
.2
3.4
3.6
MeO group is in the plane of the C=C bond and the carbonyl
group comes out of the plane, is less favorable (the overall
energy is –306.485469 Hartree) than the cis-form (cf. Table 3).
Fig. 1. Temperature dependence of the rate constant of 2-butyl-
thiopropenal cyclodimerization (k) (heptane is the solvent).

Mechanism of alkylthiopropenals cyclodimerization Russ.Chem.Bull., Int.Ed., Vol. 49, No. 12, December, 2000 1979
Table 3. Energies of molecules and electron density distribution (according to Mulliken) in conformers of 2-methoxy- (3a,b),
2
-methylthiopropenals (4a,b), and propenal (5a,b) calculated by the B3LYP/D95++(d,p) method
H
H
H
H
H
,8,9
H
9,10,11
H
7,8,9
H
H 5,6
1
H
H 5,6
1
H
4
7
7,8,9
7
7
2
3
2
2
1
1
1
H
2
H
2
O
O
O
S
H
H
H
H
3
H11
2
3
H11
3
12H
5
6O
5
H8
12H
5
6O
5
H
3
3
4
1
4
4
10,11
4
8
H8
O
O4
5b
H
O6
H10
H12 H7
O6
H10
H12
4b
H
5
a
3
a
3b
4a
1
Mol-
ecule
E *
q/a.u.
C(1)
O(2),
C(2),
S(2)
C(3),
O(3)
C(4),
O(4)
C(5),
H(5)
O(6),
H(6)
H(7)
(H(8))
[H(9)]
H(10)
(H(11))
[H(12)]
3
3
4
4
a
b
a
b
–306.4997769** –0.433399 –0.328905
0.657223 –0.503881 –0.101188 –0.386915
0.173779
0.184830) (0.196819)
0.194862] [0.137822]
0.194318
0.207196) (0.182923)
0.208798] [0.147284]
0.203144
0.202586) (0.224637)
0.197524] [0.169759]
0.208954
(
[
–306.5037163*** –0.831332
0.755334 –0.337837 –0.399536
0.052586 –0.374084
0.194551
(
[
–629.4618867
–629.464895
–0.573199 –0.292121
0.293971 –0.232724 –0.037616 –0.351819
0.195858
(
[
–0.582509 –0.181778
0.377308 –0.442599
0.036532
–0.364077
0.242825
0.177478
(
[
0.190417) (0.228783)
0.193234] [0.124385]
5
5
a
b
–191.95216
–0.456254
–0.530280
0.160073 –0.059190 –0.356560
0.245692 –0.050737 –0.370319
0.210169
0.185806
0.183572
0.191272
0.186281
0.131907)
0.200807
0.127760)
—
(
(
–191.955390
—
*
*
Total energies in Hartree units.
* The energy is presented for a molecule in which the Me group is out of the plane of the double bonds and the O atom of the ether
group, and the dihedral angle is 71°.
** The energy is presented for a molecule in which the Me group is out the plane of the double bonds and the O atom of the ether
*
group, and the dihedral angle is –44.7°.
substituent R does not affect the reaction rate.
Average values of the rate constants for dimerization
(
gradually lowers. This likely explains the retardation of
aldehyde dimerization in the series of heteroatoms
k•10 /L mol s–1) of α-alkylthioacroleins in heptane
4
–1
at 20 °C and their standard deviations at R = Pr, Bu,
and C H are 0.65±0.19, 1.21±0.31, and 0.33±0.049,
respectively.
These findings allow us, by analogy with the
Table 4. The LUMO and HOMO energies for oxabutadienes
6
13
(
eV) calculated by the Â3LYP/D95++(d,p) method
Oxabutadiene
∆E*trans-trans
ELUMO
EHOMO
data1,3,17,18 on the Diels—Alder reaction, to classify
reaction (1) as a pericyclic process, which is controlled
by orbital interaction. The stabilization energy for two
molecular orbitals of approaching molecules is inversely
proportional to the difference in the energies of their
0.15160
0.01339
0.00826
0.00733
–0.01181
0.08542
–0.23702
–0.27680
–0.31008
–0.34795
–0.38984
MeS
–
O
MeO
O
–
1
levels , i.e., the narrower the energy gap, the stronger
the interaction17 and the corresponding contribution to
0.178441
0.02157
0.01688
0.00315
–0.00866
0.08041
–0.25882
–0.27494
–0.33595
–0.36926
–0.40831
the stabilization of filled orbitals.19 The HOMO and
LUMO mostly contribute to the stabilization energy.20
The orbital energies of the aldehydes under study
were calculated by the B3LYP/D95++(d,p) method21
–
0
.18890
0.02076
–0.27152
–0.30493
–0.40413
–0.40919
–0.43099
(
Table 4). As can be seen in Table 4, the substitution of
0
0
.01454
.00569
the H atom in position 3 for the O atom and then for the
S atom enhances the HOMO energy. A comparison of
the energy difference between the HOMO and LUMO
for 2-methylthio- and 2-methoxypropenals and unsub-
stituted propenal shows that the stabilization energy
O
–0.00842
0.08286
–
Note. ∆E* = ELUMO – ÅHOMO
.

1
980
Russ.Chem.Bull., Int.Ed., Vol. 49, No. 12, December, 2000
Keiko et al.
S > Î > Í. This conclusion is in agreement with the
sequence of the experimental rate constants.9
5. L. L. Dmitrieva, V. P. Zinov'eva, G. I. Sarapulova, O. B.
Bannikova, and N. A. Nedolya, Zh. Org. Khim., 1996, 32,
1
348 [Russ. J. Org. Chem., 1996, 32, No. 9 (Engl. Transl.)].
6
7
. L. K. Korostyleva, Ph. D. (Pharm.) Thesis, Moscow Medical
Akad. im. I. S. Sechenov, Moscow, 1997 (in Russian).
. Yu. A. Khomov, I. V. Pepelyaeva, N. V. Koksharova, and
G. P. Vdovina, Tez. dokl. ÕÕ Vseros. konf. po khimii i
tekhnologii organicheskikh soedinenii sery [Abstrs. XX All-Russ.
Conf. on Chemistry and Technology of Organic Sulfur
Compounds], Kazan', 1999, p. 232 (in Russian).
. N. A. Keiko and L. G. Stepanova, Izv. Akad. Nauk SSSR,
Ser. Khim., 1972, 2516 [Bull. Acad Sci. USSR, Div. Chem.
Sci., 1972, 21, 2446 (Engl. Transl.)].
Experimental
1
3
C
NMR spectra were obtained on a Jeol FX-90
spectrometer (89.95 MHz) in CDCl3 with HMDS internal
standard.
A Specord IR-75 spectrometer with a Carl Zeiss Jena
temperature cuvette and calibrated thermocouple was used for
kinetic measurements. Monomeric 2-alkylthiopropenals prepared
8
9
1
0
by retrodiene synthesis
were contaminated by the dimers
immediately after distillation. Therefore, the initial concentration
of the monomer was determined by 1Í NMR from the ratio of
the integral intensities of the singlets from protons in the CHO
groups of the monomer and dimer molecules, taking into
account the weighted portion of aldehyde and the volume of the
solvent. It was found in preliminary experiments that the integral
intensities of these signals correlate exactly with those of the
. N. A. Keiko, L. G. Stepanova, N. N. Vainberg, O. B.
Bannikova, and M. G. Voronkov, Zh. Org. Khim., 1983, 19,
4
80 [J. Org. Chem. USSR, 1983, 19, No. 3 (Engl. Transl.)].
1
1
0. N. A. Keiko, Yu. A. Chuvashev, L. G. Stepanova, L. I.
Larina, G. I. Sarapulova, and M. G. Voronkov, Zh. Org.
Khim., 1999, 35, 41 [Russ. J. Org. Chem., 1999, 35, No. 1
(
Engl. Transl.)].
protons at the double bond (Í Ñ= of a monomer and ÍÑ= of a
2
1. N. A. Keiko, L. G. Stepanova, Yu. A. Chuvashev, L. I.
dimer) and therefore associates (for example, trimers formed
through the carbonyl group of the monomer or dimer) do not
form under the experimental conditions. The 1Í NMR spectra
were recorded on a Bruker DPX-400 (400 Hz) spectrometer.
Kinetic measurements were performed in a stationary cuvette
of the IR spectrometer with the use of as-distilled mixtures of
the monomer and dimer of 2-alkylthiopropenal. The kinetic
data were calculated from changes in the absorbance of the
absorption bands of the Ñ=Ñ or Ñ=Î groups of the monomer
or dimer. The scale of measurement was 15/100 cm–1, the time
of measurement was 11 min, and the resolution in the range of
Larina, and M. G. Voronkov, Izv. Akad. Nauk, Ser. Khim.,
1
999, 2020 [Russ. Chem. Bull., 1999, 48, 1997 (Engl.
Transl.)].
1
1
1
2. H. E. Avery, Basic Reaction Kinetics and Mechanisms,
Lanchester Polytechnik, Coventry, Macmillan, 1974.
3. T. L. Gilchrist and R. C. Storr, Organic Reaction and Orbital
Symmetry, University Press, Cambridge, 1972.
4. H. Eyring, S. H. Lin, and S. M. Lin, Basic Chemical
Kinetics, Wiley, New York—Chichester—Brisbane—To-
ronto, 1980.
5. N. A. Keiko, Yu. A. Chuvashev, L. G. Stepanova, O. B.
Bannikova, and M. G. Voronkov, Izv. Akad. Nauk, Ser.
Khim., 1996, 188 [Russ. Chem. Bull., 1996, 45, 180 (Engl.
Transl.)].
1
1
1
550—1700 cm–1 was 1 cm–1. The correctness of the analytical
procedure is based on the fact that measurements were conducted
simultaneously for several absorption bands (ν(Ñ=Ñ), ν(Ñ=Î)).
The dimerization constant was calculated as an average of
6. A. B. Koldobskii, V. V. Lunin, and S. A. Voznesenskii,
Zh. Org. Khim., 1991, 27, 2615 [J. Org. Chem. USSR, 1991,
5
—9 values obtained for the same absorption band. The second
reaction order was observed at an initial concentration of
α-alkylthioacroleins from 0.04 to 0.87 mol L–1
2
7, No. 12 (Engl. Transl.)].
7. J. Sauer and R. Sustmann, Angew. Chem., Int. Ed. Engl.,
980, 19, 779.
8. K. N. Houk, J. Gonzalez, and Y. Li, Acc. Chem. Res.,
995, 28, 81.
9. A. P. Marchand, B. Gangnly, and R. Shukla, Tetrahedron,
998, 54, 4477.
.
1
1
1
To study the photochemical or radical effects on the
cyclodimerization process, the synthesis of 2-formyl-2,5-
dibutylthio-3,4-dihydro-2Í-pyran was carried out according to
1
1
a
procedure described previously8 in the light without
hydroquinone and in the dark in the presence of hydroquinone
1
(
0.3 mol.%). In both cases, the same amount of cyclodimer was
2
2
0. R. Sustmam, Tetrahedron Lett., 1971, 2717.
found by 1Í NMR.
1. M. J. Frisch, G. W. Trucks, H. B. Schlegel, G. E. Scuseria,
M. A. Robb, J. R. Cheeseman, V. G. Zakrzewski, J. A.
Montgomery, Jr., R. E. Stramann, J. C. Burant, S. Dapprich,
J. M. Millam, A. D. Daniels, K. N. Kudin, M. C. Strain,
O. Farkas, J. Tomasi, V. Barone, M. Cossi, R. Cammi,
B. Mennucñi, C. Pomelli, C. Adamo, S. Clifford,
J. Ochterski, G. A. Petersson, P. Y. Ayala, Q. Cui,
K. Morokuma, D. K. Malick, A. D. Rabuck,
K. Raghavachari, J. B. Foresman, J. Cioslowski, J. V. Ortiz,
B. B. Stefanov, G. Liu, A. Liashenko, P. Piskorz,
I. Komaromi, R. Gomperts, R. L. Martin, D. J. Fox,
T. Keith, M. A. Al-Laham, C. Y. Peng, A. Nanayakkara,
C. Gonzalez, M. Challacombe, P. M. W. Gill, B. Johnson,
W. Chen, M. W. Wong, J. L. Andres, C. Gonzalez,
M. Head-Gordon, E. S. Replogle, and J. A. Pople,
GAUSSIAN-98, Revision A6, Gaussian, Inc., Pittsburgh
The 13C NMR spectrum of 2-butylthiopropenal (δ): 21.85
(
(
CH ); 29.34 and 29.79 (CH CH ); 38.51 (SCH ); 126.10
3 2 2 2
H C=); 147.63 (=CSBu); 190.16 (CH=O).
2
The 13C NMR spectrum of 2-ethoxypropenal (δ): 13.07
(
CH ); 62.90 (OCH ); 102.02 (=CH ); 157.82 (=C—O);
3
2
2
1
87.24 (CHO).
The work was financially supported by the Russian
Foundation for Basic Research (Project No. 99-03-33057).
References
1
2
3
4
. L. F. Tietze, G. Kettschau, J. A. Gewert, and
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1
986, Erevan, Akad. Nauk Arm. SSR, 187 pp. (in Russian).
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Chemistry, Ed. P. Metz, Springer, 1997, 189, 120 pp.
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(
PA), 1998.
Received February 4, 2000;
in revised form June 15, 2000
1
982, 47, 5246.