Experimental and Theoretical Justification for the Regiospecific Cycloaddition of Levopimaric Acid to 2-Acetyl- or 2-(Methoxycarbonyl)-1,4-Benzoquinone

Article abstract of DOI:10.1007/s10600-015-1506-2

New 4a-quinopimaric acid derivatives were synthesized via a Diels-Alder reaction of levopimaric acid with 2-acetyl- or 2-(methoxycarbonyl)-1,4-benzoquinone and were characterized using elemental analysis and NMR spectroscopy. Thermodynamic and activation

Full text of DOI:10.1007/s10600-015-1506-2

DOI 10.1007/s10600-015-1506-2
Chemistry of Natural Compounds, Vol. 51, No. 6, November, 2015
EXPERIMENTAL AND THEORETICAL JUSTIFICATION
FOR THE REGIOSPECIFIC CYCLOADDITION
OF LEVOPIMARIC ACID TO 2-ACETYL- OR
2-(METHOXYCARBONYL)-1,4-BENZOQUINONE
*
G. F. Vafina, S. S. Borisevich, A. R. Uzbekov,
A. I. Poptsov, L. V. Spirikhin, and S. L. Khursan
New 4a-quinopimaric acid derivatives were synthesized via a Diels–Alder reaction of levopimaric acid with
2-acetyl- or 2-(methoxycarbonyl)-1,4-benzoquinone and were characterized using elemental analysis and
NMR spectroscopy. Thermodynamic and activation parameters of the Diels–Alder reactions of levopimaric
acid and a model diene (7-isopropyl-1,2,3,4,4a,5-hexahydronaphthalene) with 2-acetyl- or
2-(methoxycarbonyl)-1,4-benzoquinone were calculated by density-functional theory in order to explain the
observed regioselective cycloaddition.
Keywords: diene synthesis, quinopimaric acid, density-functional theory.
The reaction of levopimaric acid with quinones is one of the most interesting diene syntheses, which are promising
methods for synthesizing polycyclic compounds. This is due to the fact that many quinone derivatives of diterpenic acids have
recently exhibited biological activity including antitumor and antiviral [1]. Several levopimaric-acid derivatives
(dihydroquinopimaric acid, adducts with 2-acetylaminoquinone, sulfonylnaphthoquinone, and 3-hexylthio-2-thiolen-4-one-
1,1-dioxide) acted as anti-inflammatory agents [1]. The diene-synthesis reaction of levopimaric acid with 2-acetyl- or
2-methoxycarbonyl-1,4-benzoquinone is interesting with respect to the potential discovery of optically active compounds
with biological activity.
O
O
H
R
2
3
2
3
12a
4a
12a
4a
+
R
H
O
O
O
COOH
R
COOH
4a, 5a
4b, 5b
+
O
O
O
COOH
R
2
12a
4a
1
2, 3
3
+
R
O
O
2, 4: R = -C(O)CH ; 3, 5: R = -C(O)OCH
3
3
COOH
COOH
4c, 5c
4d, 5d
ꢀHꢁ (4a) = – 3.5 kJ/mol; ꢀHꢁ (4b) = – 16.3 kJ/mol
295
295
ꢀHꢁ (4c) = – 33.6 kJ/mol; ꢀHꢁ (4d) = – 34.9 kJ/mol
295
295
ꢀHꢁ (5a) = – 20.7 kJ/mol; ꢀHꢁ (5b) = – 25.7 kJ/mol
295
295
ꢀHꢁ (5c) = – 38.4 kJ/mol; ꢀHꢁ (5d) = – 40.2 kJ/mol
295
295
Ufa Institute of Chemistry, RussianAcademy of Sciences, 450054, Ufa, Prosp. Oktyabrya, 71, e-mail: vafina@anrb.ru.
Translated from Khimiya Prirodnykh Soedinenii, No. 6, November–December, 2015, pp. 964–969. Original article submitted
April 10, 2015.
©
1120
0009-3130/15/5106-1120 2015 Springer Science+Business Media New York

In continuation of studies on the synthesis of new quinopimaric-acid derivatives [2], we studied the Diels–Alder
reaction of levopimaric acid (1) contained (~30%) in pine tar with 2-acetyl- (2) and 2-(methoxycarbonyl)-1,4-benzoquinone
(3). The reaction occurred stereo- and regiospecifically during seven days to give only regioisomers 4a and 5a in 99 and 73%
yields, respectively.
The position of the R substituent was determined using PMR and NMR correlation spectra of 4a. Thus, the PMR
spectrum showed two doublets at ꢂ 5.97 and 6.03 ppm with SSCC 10.2 Hz that were consistent with protons of a 2(3) double
13
bond. The proton of the other double bond resonated as a singlet at ꢂ 5.33 ppm. A singlet at ꢂ 71.82 ppm in the C NMR
spectrum belonged to C-4a and indicated that the acetyl was located at this position. The proton with chemical shift (CS)
3.25 ppm in the HSQC spectrum correlated with C-12a (ꢂ 56.40 ppm). The proton with CS 2.79 ppm gave a cross peak with
C-12 (ꢂ 40.84 ppm). Proton H-12a (ꢂ 3.25 ppm) gave cross peaks with C-4a (ꢂ 71.82 ppm), C-4b (ꢂ 46.72 ppm), C-11
1
1
(ꢂ 30.13 ppm), C-12 (ꢂ 40.84 ppm), and C-13 (ꢂ 148.52 ppm) and with the three ketones C-1, C-4, and COMe. The H– H
COSY spectrum of H-12a indicated correlations with H-12 and H-11ax although the SSCC between them was <1 Hz.
The NOESY spectrum showed correlations of the acetyl methyl protons with H-10b and H-12a. This confirmed that it had the
ꢃ-position and that rings D and E were cis-fused. The same scenario was observed for 5a.
Thus, addition of 2-substituted-1,4-benzoquinones 2 or 3 to levopimaric acid (1) formed a single adduct in which the
substituent (acetyl or methoxycarbonyl) was located in the 4a-position at the ring fusion site. This contrasted with all previously
synthesized quinopimaric-acid derivatives, in which the substituents were terminal (on the side of the C-2=C-3 double bond)
[2]. On one hand, this agreed with previous results [3–5] for dienophiles 2 and 3 in diene syntheses. On the other, a diene
synthesis of in-situ-generated 2-acetylbenzoquinone with 1-methyl-1,3-butadiene in THF–TFA and Pb O proceeded
3
4
anomalously and formed a product in which the acetyl was located on the terminal C-2=C-3 double bond [6]. The Diels–Alder
reaction of levopimaric acid with dienophiles 2 and 3 was investigated using density-functional theory in order to obtain
additional information regarding the dominant steric effects for this system.
NMR spectral data showed unambiguously that the reaction of levopimaric acid with 2-acetyl- and
2-(methoxycarbonyl)-1,4-benzoquinones (2 and 3) formed only the endo-adducts. This phenomenon is well-known in the
literature [7] and is called the Alders endo-effect. Therefore, we did not analyze the possible exo-directed cycloaddition. It
was obvious considering this model limitation that the addition of 2 and 3 to 1 could form four endo-oriented regioisomers
4a–d (5a–d), the structures of which depended on the positioning of the second reagent relative to the acid reactive center.
The studied reaction was exothermic for both benzoquinones. The quantity ꢀ H°
was greatest for the reaction
r
295
leading to adducts 4a and 5a. The enthalpies of formation of regioisomers 4a–d and 5a–d [B3LYP/6-311+G(d,p)] were
calculated considering solvation (CH Cl ) at 295 K. The result indicated that the formation of these compounds was least
2
2
probable with respect to thermodynamic stability. However, regioisomers 4a and 5a were the only reaction products according
to NMR studies (see above). Therefore, the preferential formation of 4a (5a) was due to kinetic factors, i.e., the faster
formation of these isomers due to differences in the activation energies for forming regioisomers 4a–d (5a–d). This hypothesis
was checked by locating all four possible transition states (TS) for the [4+2]-cycloaddition reaction using the reactions of 2
and 3 with the model diene 7-isopropyl-1,2,3,4,4a,5-hexahydronaphthalene (6) as examples. Diene 6 was selected as a simplified
analog of 1 in order to conserve computing time and preserved all structural features of the levopimaric-acid reaction centers.
The numbering for model products 7a–d (8a–d) is the same as for adducts 4a–d (5a–d).
O
O
R
H
+
H
R
O
O
O
7a, 8a
7b, 8b
R
+
O
O
O
R
O
6
2, 3, 7, 8
+
R
2, 7: R = -C(O)CH
3, 8: R = -C(O)OCH
3
O
3
7c, 8c
7d, 8d
1121

ꢄ
TABLE 1. Enthalpies of Reaction (ꢀ Hꢁ) and Activation (ꢀH ) at the B3LYP/6-311+G(d,p) Level for the Reaction of 6 with
r
2-Acetyl- and 2-(Methoxycarbonyl)-1,4-benzoquinones
ꢀHꢄ, kJ/mol
ꢀrHꢁ295, kJ/mol
ꢀHꢄ, kJ/mol
ꢀrHꢁ295, kJ/mol
Reaction
Reaction
70.6
88.8
85.3
84.6
–19.4
–30.3
–47.1
–48.3
75.9
93.1
106.6
103.8
–35.9
–39.2
–49.4
–53.1
6 + 2ꢅ7a
6 + 2ꢅ7b
6 + 2ꢅ7c
6 + 2ꢅ7d
6 + 3ꢅ8a
6 + 3ꢅ8b
6 + 3ꢅ8c
6 + 3ꢅ8d
2.05
12a
2.45
1.95
12a
2.06
12a
3
2.49
2.02
2.96
2.41
4a
12a
2
4a
4a
3
4a
2
2
3
2
3
–1
–1
–1
–1
TS (7a) ꢆ
= 338i cm
TS (7b) ꢆ
= 396i cm
TS (7c) ꢆ
= 424i cm
TS (7d) ꢆ = 420i cm
imag
imag
imag
imag
Fig. 1. Transition states (TS) for the reaction of 7-isopropyl-1,2,3,4,4a,5-hexahydronaphthalene with 2-acetyl-1,4-benzoquinone at
°
the B3LYP/6-311+G(d,p) level; bond lengths are given in A; the value of the only imaginary frequency ꢆ
is given for each TS.
imag
The Diels–Alder reaction of 6 with 2 and 3 formed cyclic TS with similar geometric parameters. The presence of a
single imaginary frequency in the calculated TS vibrational spectrum confirmed that they were valid. Figure 1 shows the
structures of the activated complexes of the four possible adducts from the Diels–Alder reaction of 6 with 2 as examples.
The activated complexes and products from the reaction of 6 with 2 and 3 were localized on the system potential-
#
energy surface. This allowed the activation energy ꢀH and enthalpies of reaction ꢀ H° to be calculated for the corresponding
r
directions with consideration of solvation (CH Cl ) at 295 K and 1 atm. Table 1 lists the results.
2
2
The fact that the thermodynamic stabilities of 7a–d (8a–d) followed the same order as those of 4a–d (5a–d) confirmed
that the simplified model was valid (Table 1). Model product 7a (8a) was thermodynamically the least stable. Therefore, its
preferential formation was explained by other factors. In fact, our calculations showed that the barrier height of the heat of
#
formation ꢀH for 7a (8a) was the lowest. The difference in the TS energies was 15 kJ/mol and greater. This indicated that the
other isomers formed negligibly slowly compared to 7a (8a).
Thus, DFT calculations confirmed theoretically that 4a and 5a were formed exclusively in our experiments. Let us
discuss briefly the effects of the cycloaddition regioselectivity using our calculations.
Frontier molecular orbitals are often and successfully used to explain the course of Diels–Alder reactions. An orbital
diagram (Fig. 2) that was constructed using our results showed as expected that the course of the reaction of 1 (6) with 2 (3)
was controlled by interaction of the highest occupied molecular orbital (HOMO) of the diene with the lowest unoccupied
molecular orbital (LUMO) of the mono-substituted benzoquinone. Because the latter displays electrophilic properties, the
C=C bond with elevated electrophilicity due to the electron-accepting effect of the –COMe (–COOMe) substituent will be the
more reactive of the two centers in 2 (3). Figure 2 shows that more strongly accepting substituents gave lower LUMO energies
and lower energy splitting for the HOMO–LUMO pair. The cycloaddition was favored as the frontier orbitals drew closer.
Therefore, the acetyl- or (methoxycarbonyl)-substituted C=C bond in 2 or 3 was more reactive than the unsubstituted one
despite the possible steric hindrance. Furthermore, the order of reactivities of the mono-substituted benzoquinones from DFT
calculations agreed fully with the experimental sequence for diene syntheses of benzoquinones [8].
The regiospecificity of the reaction was also apparent in the positioning of the acetyl or methoxycarbonyl substituent
exclusively in the 4a-position of quinopimaric acid. Our DFT calculations confirmed the conclusion based on NMR studies
and provided a theoretical explanation of the observed effect.
1122

O
O
R
E, eV
-0.71
-5.54
-3.63
-7.54
-3.78
-7.63
-3.95
-7.81
-4.07
-4.24
-7.57
-4.60
-8.41
-7.78
R = -CN> -C(O)Me > -C(O)OMe > -H > -Me > -OMe
Increasing reactivity
Fig. 2. Frontier orbital energies [B3LYP/6-311+G(d,p)] for diene 6
and several substituted 1,4-benzoquinones.
The studied transformations occurred through the two-center addition mechanism typical of Diels–Alder reactions
[7]. However, the C–C bonds in the TS were not formed synchronously (Fig. 1). The nature of the asynchronicity and its
scale, which was estimated as the difference of the resulting bond lengths, varied as a function of the acetyl position. Interatomic
distance r in TS(7a), i.e., r(C12–C12a), was significantly shorter than r = r(C4b–C4a) whereas the reverse relationship of
12
4
bond lengths (r < r ) was noted for TS(7b). The effect was less pronounced in the other two TS (Fig. 1) although r > r .
4
12
4
12
The reaction of model diene 6 (and also 1) is a classical instance of the reaction of reagents containing substituents
with opposing electronic effects. The weakly electron-donating isopropyl radical in 6 affects the molecular wave function so
that the AO coefficient of the neighboring C atom (marked by a dot in the diagram) in the MO LCAO expansion for the HOMO
is increased. In a similar manner, the electron-accepting substituent in 2-acetyl-1,4-benzoquinone increases theAO coefficient
on the distal C atom of the double bond in the expansion of the LUMO of the dienophile over the basis AO. This C atom is
marked with a large dot in the diagram because the acetyl substituent displays strong accepting properties.
O
R
+
O
R = Ac
O
O
R
O
O
O
R
R
O
R
O
O
TS ( 7a)
TS ( 7d)
TS ( 7b)
TS (7c)
7a
7c
7d
7b
ꢁ
ꢀr = r – r , A
4
12
ꢁ
ꢀr = 1.01 A (7a); –0.47 (7b); 0.35 (7c); 0.40 (7d)
Only the substituted diene moiety of 6 is shown in the diagram for simplicity. The values ꢀr = r – r are shown.
4
12
The HOMO–LUMO overlap for forming the r bond is maximum in the TS corresponding to the major reaction adduct 7a.
12
As a result, the distance between C atoms marked with dots in the diagram will be much less than the length of C–C bonds
formed in the other activated complexes. This is clearly illustrated by the quantum-chemical calculations (Fig. 1).
The diagram explains correctly the TS asynchronicity in all instances. For example, if the acetyl substituent is located on the
side of the terminal C=C double bond [TS(7c, 7d)], then the moderate asynchronicity of forming the C–C bonds in the TS is
due only to the effect of the isopropyl substituent in 6. The effectiveness of orbital overlap in the TS is reflected in
#
the activation energy and explains the variation of ꢀH for the different courses of the cycloaddition (Table 1). Obviously, all
electronic effects examined using 2-acetyl-1,4-benzoquinone as an example are valid for 3.
Thus, the formation of only adducts 4a and 5a in the reaction of levopimaric acid with 2-acetyl- or 2-(methoxycarbonyl)-
1,4-benzoquinones is explained primarily by the interaction of the reagent frontier orbitals. The substituents in both reagents
affect their energy and composition. This interaction controls both the reaction energetics and its regiospecificity.
1123

EXPERIMENTAL
13
PMR and C NMR spectra were recorded in CDCl on a pulsed Bruker Avance-III spectrometer (500 MHz) at
3
1
13
13
operating frequency 500.13 MHz for H and 125.47 MHz for C. Chemical shifts in PMR and C NMR spectra are given in
ppm vs. solvent resonances. 2D correlation spectra were recorded using the standard instrument library of pulse sequences.
IR spectra of thin layers were taken on a Shimadzu instrument. Elemental analysis was performed on a Euro EA 3000
analyzer. Melting points were uncorrected and were measured on a Boetius apparatus. NMR, mass, and IR spectra were
recorded on equipment at the Khimiya CCU, UIC, RAS. Elemental analyses of all synthesized compounds agreed with those
calculated.
The course of reactions was monitored by TLC on Sorbfil PTSKh-AF-Aplates. Compounds were detected by spraying
with H SO solution (5%) followed by heating to 100–120°C. The eluent was CHCl –MeOH (50:1, 10:1, 5:1). Flash
2
4
3
chromatography was carried out over standard silica gel 60 (0.04–0.063 mm, 230–400 mesh) (Macherey–Nagel, Germany).
2-Acetyl-1,4-benzoquinone was prepared via oxidation of 2,5-dihydroxyacetophenone by Ag O [9].
2
2-(Methoxycarbonyl)-1,4-benzoquinone was prepared in two steps from 2,5-dihydroxybenzoic acid (first, methylation by
diazomethane; second, oxidation by Ag O [9]). Physicochemical data for the synthesized quinones agreed with those in the
2
literature. We used Pinus sylvestris pine tar containing ~30% levopimaric acid that was collected in spring 2012 near Nizhnii
Novgorod. The levopimaric acid content in the pine tar was determined using GC and the ratio of methyl esters of total
resinous acids that were produced by methylating pine tar with an excess of diazomethane. The product yields were calculated
per starting quinone.
Diene Synthesis Method. Pine tar (5 g) in CH Cl (50 mL) was treated with the appropriate quinone (0.05 mol) in
2
2
hexane (2.5 mL). The reaction mixture was stored in the dark at room temperature for 7 d. The solvent was vacuum distilled
(water aspirator). The residue was crystallized from petroleum ether (40–70°C).
(7R,10aR,12aS,4aS)-4a-Acetyl-13-isopropyl-7,10a-dimethyl-1,4-dioxo-4,4a,5,6,6a,7,8,9,10,10a,10b,11,12,12a-
tetradecahydro-1H-4b,12-ethenochrysene-7-carboxylic Acid (4a). C H O , quantitative yield. Acid 4a was isolated
28 36
5
20
pure as a bright-yellow powder by crystallization from MeOH–hexane, mp 75–78°C (MeOH–hexane), [ꢃ] –129° (c 1.2,
CHCl ). IR spectrum (ꢆ, cm ): 3177, 1733, 1723, 1667, 1616, 1464, 1377, 1363, 1277, 1189, 1028. H NMR spectrum
D
–1
1
3
(C D , ꢂ, ppm, J/Hz): 0.55 (3H, s, Ìå-7), 0.73–0.75 (1Í, m, Í -10), 0.76 (3H, d, J = 7.1, Ìå), 0.78 (3H, d, J = 7.1, Ìå), 0.92–
6
6
eq
0.97 (1Í, m, Í -11), 1.06 (1Í, d, J = 12.6, Í -10), 1.16 (3H, s, Ìå-10à), 1.21–1.32 (3Í, m, Í -9, Í -6, Í -9), 1.39–1.45
eq
ax
eq
eq
ax
(1Í, m, Í -6), 1.49 (1Í, d, J = 13.3, Í -8), 1.55–1.62 (1Í, m, Í -11), 1.70 (3H, s, ÌåÑÎ), 1.75 (1Í, dd, J = 13.3, 4.0,
ax
eq
ax
3
4
Í -8), 1.86 (1H, septd, J = 7.1, J = 1.7, H-15), 2.00 (1H, dd, J = 10.5, 1.6, Í-10b), 2.09 (1H, td, J = 13.6, 4.9, 4.9, Í -5),
ax
eq
2.37 (1H, dd, J = 9.6, 5.6, Í-6à), 2.50 (1H, dt, J = 13.6, 3.1, Í -5), 2.79 (1H, t, J = 0.7, Í-12), 3.25 (1H, s, Í-12à), 5.25 (1H,
ax
13
s, H-14), 5.98 (1H, d, J = 10.2, Í-2), 6.03 (1Í, d, J = 10.2, Í-3). C NMR spectrum (C D , ꢂ, ppm): 15.74 (q, Ìå), 16.57
2-3
3-2
6 6
(q, Ìå), 16.91 (t, Ñ-9), 19.75 (q, Ìå), 20.06 (q, Ìå), 22.29 (t, Ñ-6), 30.12 (q, Ìå), 30.13 (t, Ñ-11), 32.02 (t, Ñ-5), 32.57 (d,
Ñ-15), 36.53 (t, Ñ-8), 37.76 (t, Ñ-10), 37.87 (s, Ñ-10à), 40.84 (d, Ñ-12), 46.05 (d, Ñ-6a), 46.72 (s, Ñ-4b), 47.49 (s, Ñ-7), 47.98
(d, Ñ-10b), 56.40 (d, Ñ-12à), 71.82 (s, Ñ-4à), 127.46 (d, Ñ-14), 138.74 (d, Ñ-3), 143.67 (d, Ñ-2), 148.52 (s, C-13), 185.58 (s,
ÑÎÎ), 196.81 (s, Ñ-4=Î), 198.16 (s, ÑÎÌå), 202.14 (s, Ñ-1=Î).
( 7 R, 1 0 aR, 1 2 aS, 4 aS ) - 1 3 - I s o p ro p y l - 4 a - ( m e t h o x y c a r b o n y l ) - 7 , 1 0 a - d i m e t h y l - 1 , 4 - d i o x o -
4,4a,5,6,6a,7,8,9,10,10a,10b,11,12,12a-tetradecahydro-1H-4b,12-ethenochrysene-7-carboxylicAcid (5a). C H O , 73%
28 36
6
20
yield. Acid 5a was isolated pure as a bright-yellow powder by crystallization from Et O–hexane, mp 58–60°C, [ꢃ] –53°
(c 2.1, CHCl ). IR spectrum (ꢆ, cm ): 1750, 1718, 1695, 1674, 1464, 1379, 1278, 1234, 1212, 1067. H NMR spectrum
2
D
–1
1
3
(CDCl , ꢂ, ppm, J/Hz): 0.56 (3H, s, Ìå-7), 0.85 (3H, d, J = 6.9, Ìå), 0.86 (3H, d, J = 6.9, Ìå), 0.94–1.04 (1Í, m, Í -10), 1.10
3
eq
(3H, s, Ìå-10à), 1.12–1.18 (1Í, m, Í -9), 1.19–1.25 (1Í, m, Í -11), 1.27–1.38 (2Í, m, Í -6, Í -10), 1.39–1.49 (2Í, m,
eq
eq
eq
ax
Í -6, 9), 1.55 (1Í, d, J = 12.7, Í -8), 1.69–1.78 (1Í, m, Í -8), 1.78–1.85 (2H, m, H-10b, Í -11), 1.94–2.09 (2H, m,
ax
eq
ax
ax
Í -5, Í-15), 2.28–2.35 (2H, m, Í -5, Í-6à), 2.83 (1H, br.s, Í-12), 3.16 (1H, br.s, Í-12à), 3.64 (3H, s, ÑÎÎÌå), 5.44 (1H,
eq
ax
13
s, H-14), 6.45 (1H, d, J = 10.2, Í-2), 6.60 (1Í, d, J = 10.2, Í-3). C NMR spectrum (CDCl , ꢂ, ppm): 15.83 (q, Ìå),
2-3
3-2
3
16.58 (q, Ìå), 17.01 (t, Ñ-9), 19.98 (q, Ìå), 20.24 (q, Ìå), 22.01 (t, Ñ-6), 30.53 (t, Ñ-11), 31.60 (t, Ñ-5), 32.61 (d, Ñ-15),
36.52 (t, Ñ-8), 37.91 (s, Ñ-10à), 38.12 (t, Ñ-10), 40.13 (d, Ñ-12), 45.90 (s, Ñ-4b), 46.29 (d, Ñ-6a), 46.66 (s, Ñ-7), 47.81 (d,
Ñ-10b), 52.64 (q, ÑÎÎÌå), 57.05 (d, Ñ-12à), 65.71 (s, Ñ-4à), 127.51 (d, Ñ-14), 138.48 (d, Ñ-3), 143.87 (d, Ñ-2), 148.31 (s,
C-13), 170.58 (s, ÑÎÎÌå), 184.95 (s, ÑÎÎ), 194.19 (s, Ñ-4=Î), 198.42 (s, Ñ-1=Î).
1124

Procedural Aspects of the Theoretical Calculations. Theoretical calculations were performed using the Gaussian
09 quantum-chemical program [10]. The DFT–B3LYP method [11–13] with basis set 6-311+G(d,p) [14] was used to optimize
the molecular structures (reagents, TS, reaction products) and to solve the vibrational problem. It was shown [15] that results
that correlated exactly with the experimental data were obtained with acceptable time constraints if this approach was used to
estimate the thermodynamic and activation parameters of the Diels–Alder reaction.
The thermodynamic parameters were calculated for an ideal gas at 298 K and modeled experimental conditions with
CH Cl solvent (polarized continuum model [16]) at 295 K.
2
2
Quantum-chemical calculations were performed on the supercomputer at the Ufa Inst. Chem., RAS.
ACKNOWLEDGMENT
The work was sponsored by a Grant of the RF President for Leading Scientific Schools No. NSh-1700.2014.3.
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2.
G. A. Tolstikov, T. G. Tolstikova, E. E. Shul ts, S. E. Tolstikov, and M. V. Khvostov, Resinous Acids of Russian Conifers.
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