Chemistry of naphthazarin derivatives 13. Conformational analysis of 3-(alk-1-enyl)-2-hydroxy-1,4-naphthoquinones by quantum chemistry methods

Article abstract of DOI:10.1007/s11172-006-0480-z

The molecular structures of various conformers of 2-hydroxy-1,4- naphthoquinone; 3-(alk-1-enyl)-2-hydroxy-1,4-naphthoquinones; 2,5,8-trihydroxy-1,4-naphthoquinone; and 3-(alk-1-enyl)-2,5,8-trihydroxy-1,4- naphthoquinones were studied by density functional theory (B3LYP/6-31(d), B3LYP/6-31(d, p)) and ab initio (MP2/6-31G, MP2/6-31(d)) methods. The strengths of the intramolecular hydrogen bonds formed by the β-hydroxy group with the O atom at C(1) and with the double bond π-electrons of the alkenyl substituents in the quinonoid rings were estimated. The compounds studied mainly exist as rotamers with the former-type hydrogen bonds. The splitting of the quinonoid bands of the stretching vibrations of the β-hydroxy group in the IR spectra of 3-(alk-1-enyl)-2-hydroxy-1,4-naphthoquinones and 3-(alk-1-enyl)-2,5,8-trihydroxy-1,4-naphthoquinones in hexane solutions is due to the existence of rotamers formed upon internal rotation of the alkenyl substituent.

Full text of DOI:10.1007/s11172-006-0480-z

Russian Chemical Bulletin, International Edition, Vol. 55, No. 10, pp. 1729—1736, October, 2006
1729
Chemistry of naphthazarin derivatives
13.* Conformational analysis of 3ꢀ(alkꢀ1ꢀenyl)ꢀ2ꢀhydroxyꢀ1,4ꢀnaphthoquinones
by quantum chemistry methods
V. P. Glazunov,ꢀ D. V. Berdyshev, A. Ya. Yakubovskaya, and N. D. Pokhilo
Pacific Institute of Bioorganic Chemistry, FarꢀEastern Branch of the Russian Academy of Sciences,
159 prosp. 100 let Vladivostoku, 690022 Vladivostok, Russian Federation.
Fax: +7 (423 2) 31 4050. Eꢀmail: glazunov@piboc.dvo.ru
The molecular structures of various conformers of 2ꢀhydroxyꢀ1,4ꢀnaphthoquinone; 3ꢀ(alkꢀ
1ꢀenyl)ꢀ2ꢀhydroxyꢀ1,4ꢀnaphthoquinones; 2,5,8ꢀtrihydroxyꢀ1,4ꢀnaphthoquinone; and 3ꢀ(alkꢀ
1ꢀenyl)ꢀ2,5,8ꢀtrihydroxyꢀ1,4ꢀnaphthoquinones were studied by density functional theory
(B3LYP/6ꢀ31(d), B3LYP/6ꢀ31(d,p)) and ab initio (MP2/6ꢀ31G, MP2/6ꢀ31(d)) methods. The
strengths of the intramolecular hydrogen bonds formed by the βꢀhydroxy group with the
O atom at C(1) and with the double bond πꢀelectrons of the alkenyl substituents in the
quinonoid rings were estimated. The compounds studied mainly exist as rotamers with the
formerꢀtype hydrogen bonds. The splitting of the quinonoid bands of the stretching vibrations
of the βꢀhydroxy group in the IR spectra of 3ꢀ(alkꢀ1ꢀenyl)ꢀ2ꢀhydroxyꢀ1,4ꢀnaphthoquinones
and 3ꢀ(alkꢀ1ꢀenyl)ꢀ2,5,8ꢀtrihydroxyꢀ1,4ꢀnaphthoquinones in hexane solutions is due to the
existence of rotamers formed upon internal rotation of the alkenyl substituent.
Key words: ab initio quantum chemical calculations; rotamers; 2ꢀhydroxyꢀ1,4ꢀnaphthoꢀ
quinone; 3ꢀ(alkꢀ1ꢀenyl)ꢀ2ꢀhydroxyꢀ1,4ꢀnaphthoquinones; 3ꢀ(alkꢀ1ꢀenyl)ꢀ2,5,8ꢀtrihydroxyꢀ
1,4ꢀnaphthoquinones.
When investigating the prototropic tautomerism of
hydroxy derivatives of naphthazarins (5,8ꢀdihydroxyꢀ
1,4ꢀnaphthoquinones) 1 with alkenyl substituents in the
orthoꢀposition to the βꢀhydroxy group (Scheme 1) by
IR spectroscopy, we faced1 with difficulty in interpreting
the stretching bands of βꢀhydroxy groups (ν(OH)).
Scheme 1
1: R1 = H, Alk; R2 = Alk; R3 = H, OH, OMe, Cl
* For Part 12, see Ref. 1.
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 10, pp. 1667—1673, October, 2006.
1066ꢀ5285/06/5510ꢀ1729 © 2006 Springer Science+Business Media, Inc.

1730
Russ.Chem.Bull., Int.Ed., Vol. 55, No. 10, October, 2006
Glazunov et al.
The IR spectra of the compounds in hexane solutions
exhibited a doublet splitting of both the quinonoid
ν(OH) bands at 3420—3370 cm–1 corresponding to the
βꢀhydroxy groups in the quinonoid rings and the benꢀ
zenoid ν(OH) bands at 3540—3510 cm–1 corresponding
to the βꢀhydroxy groups in the benzenoid rings, the splitꢀ
ting, ∆ν(OH), being 26—39 and 14—16 cm–1, respecꢀ
tively. We suggested that the observed splitting is due to
different types of intramolecular hydrogen bonds (IMHB)
formed by the βꢀhydroxy group, namely, IMHBꢀ1
(OH...O=C(1)) in tautomer Q, IMHBꢀ1´ (OH...O—H)
with the O atom of the αꢀhydroxy group at the C(1) atom
in tautomer В, and IMHBꢀ2 (OH...π) with the polarized
πꢀelectrons of the C(1´)=C(2´) bond of the alkenyl subꢀ
stituent in isomers Q´ and B´.
study1 and required an additional investigation. In this
work, using quantum chemical methods, we carried out
the conformational analysis of molecules 1 and 5, estiꢀ
mated the strengths of the IMHBꢀ1 and IMHBꢀ2, perꢀ
formed the normalꢀmode analysis and calculated vibraꢀ
tion frequencies of the possible rotamers formed upon
internal rotation of βꢀhydroxy and alkenyl groups. Based
on the results obtained, the experimental IR spectra of
the compounds under study were interpreted. Since comꢀ
pounds 1 exist in solutions mainly as tautomers Q (the
βꢀhydroxy group is in the quinonoid ring),1 only these
forms were considered in this study.
Results and Discussion
Previously1 we excluded the following reasons for splitꢀ
ting of the ν(OH) bands in the IR spectra of compounds 1
and 5: the existence of intermolecular complexes of difꢀ
ferent compositions, coupling with overtones or comꢀ
pound tones, and the presence of 1,5ꢀtautomers. The posꢀ
sibility of splitting of the ν(OH) bands due to the fact that
these compounds can exist as several rotamers formed
upon internal rotation of the alkenyl substituent, the
βꢀhydroxy group, or both (Scheme 2) was not considered
earlier. In rotamers а and b, the βꢀhydroxy group forms an
IMHBꢀ1 with the oxygen atom of the O=C(1) carbonyl
group, while in rotamer с, a weak multicenter IMHBꢀ2
(OH...π) is formed. Rotamer d corresponds to the conꢀ
figuration of the molecule with formally broken IMHBꢀ2
and completely broken IMHBꢀ1.
The OH...π hydrogen bond was first detected by
IR spectroscopy for 2ꢀphenylphenol (2).2 This type of
bond has been studied for оꢀvinylphenol (3) and its deꢀ
rivatives3—5 and for allylphenol (4) and its derivatives6,7
where polarized πꢀelectrons of the double bond act as
electron donors.
Unlike other known IMHB types (O—H...O,
N—H...O, N—H...N, S—H...O), in this case a dynamic
equilibrium between the rotamers with bonded and free
OH groups is possible at room temperature. In a later
study, based on ab initio calculations, the OH...π interacꢀ
tion was suggested to be mainly electrostatic in characꢀ
ter;6 however, the term "hydrogen bond" is still used.7
The magnitudes of the splitting of the benzenoid and
quinonoid ν(OH) bands in the IR spectra of compounds 1
are difficult to interpret in terms of the model according
to which the components of the doublet refer to isomers
with different IMHBs. On the one hand, dissociation of
the OH...π bond in molecule 3 is characterized by
∆ν(OH) = 54 cm–1, which is ∼4 times greater than the
splitting of the benzenoid bands and ∼2 times greater than
the splitting of the quinonoid bands (see above). On the
other hand, the IMHBꢀ2 is a very weak hydrogen bond
with a strength of about 0.75—1.5 kcal mol–1,3 whereas
according to estimates made in this study, the strength
of the IMHBꢀ1 exceeds 6 kcal mol–1. A similar splitting,
∆ν(OH) = 30 cm–1, was also observed for 2ꢀhydroxyꢀ
1,4ꢀnaphthoquinone 5 with an alkenyl substituent in the
orthoꢀposition to the βꢀhydroxy group.1
Scheme 2
R1, R2 = H, Me, Et, But (1, 5); R3 = OH (1), H (5)
Detailed investigation of the reasons for the splitting
of the ν(OH) bands was beyond the scope of the previous
Compounds 1 and 5 differ basically from vinylꢀ
phenol 3 in that the βꢀhydroxy group is simultaꢀ

Rotamers of alkenylhydroxynaphthoquinones
Russ.Chem.Bull., Int.Ed., Vol. 55, No. 10, October, 2006
1731
Scheme 3
i. ∆E7d = 7.92 kcal mol–1; ii. ∆E7c = 5.65 kcal mol–1; iii. ∆E7b = 0.43 kcal mol–1 (according to MP2/6ꢀ31(d) calculations).
6: R1 = H, R2 = But; 7: R1 = H, R2 = Me; 8: R1 = R2 = Et
neously in orthoꢀposition to the carbonyl and vinyl
groups, which can form the IMHBꢀ1 or IMHBꢀ2, reꢀ
spectively. The presence of carbonyl groups in poꢀ
sitions 1 and 4 changes substantially the condiꢀ
tions of internal rotation of the hydroxy and alkenyl
groups. Due to these differences, the ratio of the conꢀ
tents of the rotamers with and without the IMHBꢀ2 is
expected to differ markedly from their ratio for comꢀ
pound 3.
Density functional (B3LYP/6ꢀ31(d,p)) and the
secondꢀorder Møller—Plesset perturbation theory
(MP2/6ꢀ31(d)) calculations of the total energies E =
E0 + ZPE (E0 is the groundꢀstate electronic energy, ZPE
is the zeroꢀpoint vibrational energy) for molecule 7
(Scheme 3) showed that rotamer а (Table 1), in which the
βꢀhydroxy group forms IMHBꢀ1 and the alkenyl double
bond is as close to it as possible, is the most stable of the
four possible rotamers. According to B3LYP/6ꢀ31(d,p)
calculations, rotamer 7а has a planar structure, while the
MP2/6ꢀ31(d) calculations predict a nonplanar structure
of this rotamer.
nient to compare the rotamer stabilities using relative
energies
∆EYx = E(Yх) – E(Yа),
where Y is the number of the compound, x = b—d is the
rotamer type. The MP2/6ꢀ31(d) and B3LYP/6ꢀ31(d,p)
calculations give similar ∆E7b values of 0.43 and
0.49 kcal mol–1, respectively.
The third in stability is rotamer 7с. Geometry optimiꢀ
zation for this rotamer carried out by both methods results
in a nonplanar structure, the MP2ꢀcalculated dihedral
angles θOH, θC=C, and θcycl being equal to 5.92, 48.20,
and 7.86°, respectively. The relative energy of rotamer 7c
with broken IMHBꢀ1 (∆E7c) is 8.05 (B3LYP/6ꢀ31(d,p))
or 5.65 kcal mol–1 (MP2/6ꢀ31(d)), which is an order
of magnitude higher than the relative energy of rotaꢀ
mer 7b.W
The most unstable rotamer is 7d with the relative enꢀ
ergy ∆E7d = 7.92 (MP2/6ꢀ31(d)) and 9.47 kcal mol–1
(B3LYP/6ꢀ31(d,p)). Like rotamer 7c, compound 7d is
nonplanar: according to MP2 calculations, θOH = 11.51°,
θC=C = 143.31°, and θcycl = 8.65°. Thus, the stability of
rotamers of alkenylnaphthoquinone 7 decreases in the
order 7a > 7b > 7c > 7d.
The strengths of the O—H...O and OH...π bonds in
molecule 7 can be compared by estimating the strength of
IMHBꢀ1 as the energy difference between rotamers 7b
and 7d
The
θOH
MP2ꢀcalculated
(H(8)—O(7)—C(2)—C(3))
dihedral
and
angles,
θC=C
(C(2´)=C(1´)—C(3)—C(2)), which characterize the
deviation of the hydroxy and alkenyl groups from the
quinonoidꢀring plane, are 176.36 and –4.07°, respectively,
and the dihedral angle θcycl (C(5)—C(4)—C(3)—C(2)),
which characterizes the distortion of the quinonoid
ring, is equal to 8.36°. B3LYP and MP2 techniques deꢀ
scribe very differently the spatial structures of the
type 7 compounds, especially the substantial deviation
of atoms of the =C(2´)HMe group and the hydrogen
atom of the βꢀhydroxy group from the naphthoquinonoid
plane and the outꢀofꢀplane distortion of the quinonoid
nucleus.
∆HIMHBꢀ1 = ∆E7b→7d = E7d – E7b
,
and the strength of IMHBꢀ2 as the energy difference beꢀ
tween rotamers 7d and 7c
∆HIMHBꢀ2 = ∆E7c→7d = E7d – E7c
.
The next in stability is rotamer 7b. B3LYP/6ꢀ31(d,p)
calculations predict a planar structure, while the
MP2/6ꢀ31(d) method predicts a nonplanar structure of
this species. The θOH, θC=C, and θcycl dihedral angles are
176.77, –178.03, and 10.18°, respectively. It is conveꢀ
In the former case, rotamer b was chosen as the referꢀ
ence point due to the most distant position of the double
bond of the alkenyl substituent from the βꢀhydroxy group.
In estimating the strength of IMHBꢀ2, rotamer 7d with
broken hydrogen bonds was taken as the reference point.

1732
Russ.Chem.Bull., Int.Ed., Vol. 55, No. 10, October, 2006
Glazunov et al.
Table 1. Total (E) and relative (∆E) energies with allowance for the zeroꢀpoint vibrational energy (ZPE), geometric parameters (θ
,
OH
θ
C=C, θcycl, RO...O), rotamer contents, and calculated ν(OH) frequencies of 3ꢀalkenylꢀ2ꢀhydroxyꢀ1,4ꢀnaphthoquinones and 3ꢀalkenylꢀ
2ꢀhydroxynaphthazarins from DFT (B3LYP) and MP2 data
Rotaꢀ
mer
Calculation
method
–E/a.u.
∆E
Content
(%)
ν(ОН)
/cm–1
θ
θ
θ
cycl
RO...O/Å
OH
C=C
/kcal mol–1
deg
6a
6b
B3LYP/6ꢀ31(d,p) 844.752905
0
0
0
71.7
72.0
69.6
28.3
28.0
3537.1
3475.9
3486.9
3565.8
3502.8
3514.2
3698.6
3634.2
3793.0
3727.8
3540.9
3478.3
3491.7
3518.4
3567.0
3504.0
3514.9
3544.1
3701
180.00
180.00
176.99
180.01 –179.81
179.98 –179.65
177.88 –168.89
7.71
7.71
9.54 –155.44
9.58 –154.44
0.00
0.00
–5.24
0.00
0.00
8.78
0.02
0.03
10.38
5.20
5.59
3.62
3.64
0.00
2.5718
2.5732
2.6607
2.5816
2.5827
2.6678
—
—
—
—
2.5730
B3LYP/6ꢀ31(d)
MP2/6ꢀ31
844.724613
840.961372
B3LYP/6ꢀ31(d,p) 844.752035
0.55
0.56
0.49
7.70
7.65
9.54
9.64
0
B3LYP/6ꢀ31(d)
MP2/6ꢀ31
844.723724
840.960597
30.4
6c
6d
7a
B3LYP/6ꢀ31(d,p) 844.740628
B3LYP/6ꢀ31(d) 844.712414
B3LYP/6ꢀ31(d,p) 844.737707
B3LYP/6ꢀ31(d) 844.709247
B3LYP/6ꢀ31(d,p) 726.889048
2•10–6
2•10–6
7•10–8
6•10–8
68.9
37.76
38.85
180.00
0.00
B3LYP/6ꢀ31(d)
MP2/6ꢀ31
MP2/6ꢀ31(d)
726.869472
723.711341
724.662478
0
0
0
69.6
69.6
67.4
31.2
30.4
30.4
32.6
10–6
5•10–5
10–7
10–6
79.4
69.4
176.96
176.36
180.00
—
177.64 –172.91
176.77 –178.03
–4.41
–4.07
180.00
—
8.61
8.36
0.00
—
2.5749
2.5950
2.5824
—
2.5838
2.6060
—
—
—
—
2.5820
2.6830
2.5940
2.6940
—
—
—
—
2.6056
–
2.7067
2.6278
2.6486
—
2.7056
2.6444
2.5787
2.6502
2.5856
2.5884
2.6661
2.5978
—
7b
B3LYP/6ꢀ31(d,p) 726.888335
0.47
0.49
0.49
0.43
8.05
5.65
9.47
7.92
0
B3LYP/6ꢀ31(d)
MP2/6ꢀ31
MP2/6ꢀ31(d)
726.868697
723.710567
724.661786
9.93
10.18
5.64
10.24
4.03
8.65
5.52
0.98
7.07
11.09
5.64
0.90
–0.53
3.03
0.00
–
7c
7d
8a
8b
8с
8d
9a
B3LYP/6ꢀ31(d,p) 726.876234
MP2/6ꢀ31(d) 724.653472
B3LYP/6ꢀ31(d,p) 726.873993
8.52
7.88
36.54
46.15
3622.3
3797
3702
3498
3503.4
3511
9.49 –158.77
11.51 –143.31
179.29
176.95
179.97 –140.28
178.26 –136.02
5.03
3.65
MP2/6ꢀ31(d)
B3LYP/6ꢀ31(d)
MP2/6ꢀ31
B3LYP/6ꢀ31(d)
MP2/6ꢀ31
B3LYP/6ꢀ31(d)
MP2/6ꢀ31
B3LYP/6ꢀ31(d)
MP2/6ꢀ31
724.649863
844.719821
840.957125
844.718521
840.956339
844.711526
840.951959
844.709336
840.949504
–47.15
–51.10
0
0.80
0.49
5.20
3.24
6.58
4.78
0
0
0
0
7.13
7.15
5.63
6.34
0
20.6
30.3
10–4
0.3
3515.9
3638
55.51
56.57
3545.2
3649.9
3572.8
3585.8
3522.0
3532.3
3576.2
3796.6
3728.3
3615.5
3719.7
3500.7
3490.4
3523.4
3525.8
3513.8
3550.5
3634.0
3731.0
3488.6
—
10–5
2•10–2
∼100
∼100
∼100
∼100
6•10–4
5•10–4
7•10–3
2•10–3
72.3
5.55 –122.24
4.70 —120.95
180.00
B3LYP/6ꢀ31(d,p) 610.221595
—
–
B3LYP/6ꢀ31(d)
MP2/6ꢀ31
MP2/6ꢀ31(d)
610.208160
607.621204
608.414171
–
177.58
177.82
0.00
—
2.24
—
—
—
—
—
—
6.07
5.12
0.00
—
9b
B3LYP/6ꢀ31(d,p) 610.210247
B3LYP/6ꢀ31(d)
MP2/6ꢀ31
MP2/6ꢀ31(d)
B3LYP/6ꢀ31(d)
MP2/6ꢀ31
MP2/6ꢀ31(d)
B3LYP/6ꢀ31(d)
MP2/6ꢀ31
MP2/6ꢀ31(d)
B3LYP/6ꢀ31(d)
B3LYP/6ꢀ31(d)
B3LYP/6ꢀ31(d)
MP2/6ꢀ31
610.196762
607.612235
608.404055
877.318588
873.608292
874.742102
877.318100
873.607242
874.741112
877.306562
877.303850
841.181457
837.551867
841.172957
837.546017
5.33
4.56
0.00
8.06
8.02
0.01
8.73
8.58
4.04
3.10
1.18
6.85
2.91
5.25
1.64
10a
10b
180.00
177.30
177.07
180.00
178.02 –170.71
177.46 –175.77
8.08
9.71 –156.05
178.02
175.39
2.39
0.00
0
0
75.3
74.0
27.6
24.7
–3.87
–4.08
180.00
0.57
0.66
0.62
7.55
9.25
0
0
5.33
3.67
26.0
10c
10d
11a
2•10–6
1•10–7
99.99
99.8
38.59
—
–41.11
–46.03
52.01
2.5724
2.6754
2.6291
2.6914
11b
B3LYP/6ꢀ31(d)
MP2/6ꢀ31
0.01
0.20
3649.3
—
3.02
57.74

Rotamers of alkenylhydroxynaphthoquinones
Russ.Chem.Bull., Int.Ed., Vol. 55, No. 10, October, 2006
1733
The strengths of the IMHBꢀ1 in compound 7 determined
by MP2/6ꢀ31(d) and B3LYP/6ꢀ31(d,p) calculations are
equal to 7.48 and 9.00 kcal mol–1. respectively. The
strengths of the IMHBꢀ2 calculated by the same methods
are 2.27 and 1.42 kcal mol–1, respectively. Thus, the
IMHBꢀ2 in molecule 7 is 3.3 (MP2) and 6.3 (B3LYP)
times weaker than the IMHBꢀ1.
To estimate the effect of the alkenyl substituent in the
orthoꢀposition to the βꢀhydroxy group on the strength of
the O—H...O hydrogen bond, we calculated ∆HIMHBꢀ1
for lawsone (2ꢀhydroxyꢀ1,4ꢀnaphthoquinone (9))
(Scheme 4): ∆HIMHBꢀ1 = ∆Е = E9b – E9a, which gave 7.15
(B3LYP/6ꢀ31(d)) and 6.34 kcal mol–1 (MP2/6ꢀ31(d)).
Due to these high ∆HIMHBꢀ1 values, the content of tauꢀ
tomer 9b is at most 7•10–3% (see Table 1). Therefore,
lawsone is expected to exist in solutions in aprotic nonpoꢀ
lar solvents mainly as rotamer 9a. Indeed, the IR specꢀ
trum of a solution of lawsone in CCl4 in the highꢀfreꢀ
quency region exhibits only one absorption band at
3413 cm–1, which corresponds to the stretching vibration
of the βꢀhydroxy group, involved in the formation of the
intramolecular Hꢀbond (rotamer 9а).
an increase in the ν(OH) frequency. Thus, the lowerꢀ
frequency component of the ν(OH) band at 3362 cm–1
observed in the IR spectra of alkenylhydroxynaphthoꢀ
quinone 7 in hexane refers to rotamer 7а and the higherꢀ
frequency component at 3390 cm–1 corresponds to
rotamer 7b.
The introduction of a tertꢀbutyl or ethyl substituent
into position 2´ of the substituent vinyl group (compounds
6 and 8, respectively) does not change the order in which
the rotamer stability decreases (a > b > c > d) established
for compound 7 with a simpler structure.
The spectrum of compound 8 in hexane shows a much
less pronounced splitting of the ν(OH) band, probably,
due to steric hindrances related to the mutual positions of
the methylene protons of the alkenyl substituent and the
oxygen atom of the βꢀhydroxy group. Unlike the sharp
ν(OH) doublet in the spectra of compounds 6 and 7, the
spectrum of compound 8 exhibits an asymmetric band
with a peak at 3385 cm–1 and a shoulder at ∼3398 cm–1
.
Deconvolution of the contour of the ν(OH) band into
components gives the frequency difference ∆ν(OH) =
16 cm–1 (cf. 30 and 28 cm–1 for compounds 6 and 7,
respectively). In addition, compound 8 shows highꢀ
frequency shifts of both components (3398.5 and
3382.4 cm–1) by 8.5 and 20.8 cm–1 with respect to comꢀ
pound 7.
Scheme 4
Geometry optimization by the MP2/6ꢀ31 and
B3LYP/6ꢀ31(d) methods showed that unlike compounds
6 and 7, all rotamers of compound 8 are nonplanar (see
Table 1). The steric hindrances induce a considerable
deviation of the alkenyl substituent from the molecular
plane, which decreases the conjugation of the doubleꢀ
bond πꢀelectrons with the πꢀsystem of the naphthoquinone
skeleton. As a result, the spectrum of compound 8 shows
a less pronounced splitting of the quinonoid ν(OH) band.
The theoretical ∆νb—a(OH) value for compound 8 is equal
to 13 cm–1, which is in good agreement with the observed
splitting (16 cm–1).
Conformational analysis of 2ꢀhydroxynaphthazarin deꢀ
rivative 10 (Scheme 5; the relative energies of the rotamers
(kcal mol–1) were obtained by B3LYP/6ꢀ31(d) calculaꢀ
tions) showed that the stabilities of rotamers a—d deꢀ
crease in the order established for compounds 6—8,
namely, 10a > 10b > 10c > 10d. The theoretical
∆νb—a(OH) value for compound 10 is 27—28 cm–1, which
is in good agreement with the observed splitting of the
ν(OH) quinonoid band in the experimental IR spectrum
(28 cm–1).
Comparison of the ∆HIMHBꢀ1 values for comꢀ
pounds 7 and 9 shows that the IMHBꢀ1 in molecule 7 is
7.48 – 6.34 = 1.14 kcal mol–1 stronger, probably, due to
the enhancement of electronꢀdonating (protonꢀacceptor)
properties of oxygen at the C(1) atom caused by conjugaꢀ
tion of the πꢀsystem of the alkenyl substituent with the
πꢀsystem of the quinonoid nucleus.
The unnormalized normal frequencies calculated for
compound 7 are listed in Table 1. The frequency differꢀ
ences ∆ν7b—7a(OH) = ν7b(OH) – ν7а(OH) calculated by
both methods in different basis sets are about 26 cm–1
,
which is in good agreement with the observed splitting
of the ν(OH) band in the IR spectrum of compound 7
in hexane (28 cm–1). According to calculations,
ν
7a(OH) < ν7b(OH). In rotamer 7a, the double bond of
the alkenyl substituent is most proximate to the OH group
and the distance between the O atoms of the carbonyl and
βꢀhydroxy groups RO...O (parameter determining the
strength of the IMHBꢀ1) is 2.5950 Å. In rotamer 7b
with the double bond of the alkenyl substituent distant
from the βꢀhydroxy group, RO...O increases to 2.6060 Å,
which indicates weakening of the IMHBꢀ1 resulting in
The effect of the nature of the substituent at
the C(3) atom on the characteristics of the ν(OH) band
in the IR spectra are clearly illustrated by the spectra
of 2ꢀhydroxyꢀ3ꢀphenylꢀ1,4ꢀnaphthoquinone (11)
(Scheme 6).
The orientation of the hydroxy group relative to
the C(1)=O carbonyl group determines the condiꢀ

1734
Russ.Chem.Bull., Int.Ed., Vol. 55, No. 10, October, 2006
Glazunov et al.
Scheme 5
i. ∆E10d = 9.25 kcal mol–1; ii. ∆E10c = 7.55 kcal mol–1; iii. ∆E10b = 0.57 kcal mol–1
10: R1 = H, R2 = Me
.
Scheme 6
rotamers c and d, the values of the statistically averaged
distribution function for rotation of the hydroxy and
alkenyl groups is five or more orders of magnitude lower
than the values attained near the equilibrium configuraꢀ
tions a and b.
For compounds 6—8 and 10, the statistical weights ga
and gb (percentages of rotamers а and b) at 298.15 К are
70.8 and 29.2%, 69.0 and 31.0%, 69.4 and 30.3%, and
73.0 and 27.0%, respectively. The ratios of the percentꢀ
ages of rotamers а and b for compounds 6—8 and 10 are
close to the ratios of the areas under the components of
the ν(OH) bands in the IR spectra of their hexane soluꢀ
tions, in particular, 64 : 36, 69 : 31, 66 : 34, and 70 : 30,
respectively.
We also carried out model B3LYP/6ꢀ31(d) calculaꢀ
tions of the solvent effect on the geometric and energy
parameters of the rotamers of compound 7 using the poꢀ
larizable continuum model (PCM) and cyclohexane as
an example. Corrections to the Gibbs energies (∆Gs =
Gs – G, where the subscript "s" designates the value calcuꢀ
lated with allowance for the solvation effects) of rotamers
tions under which the phenyl group rotates. Due to symꢀ
metry, each internal rotation potential Va(θC(1´)=C(2´)) and
Vb(θC(1´)=C(2´)) has four minima with equal energies,
which correspond to equivalent structures. According to
calculations, the energies of rotamers 11b are higher than
those of the most stable rotamers 11a by 3.6 (MP2/6ꢀ31)
and 5.3 kcal mol–1 (B3LYP/6ꢀ31(d)), respectively.
The content of rotamer 11b is only 0.20 (MP2) and
0.01% (B3LYP). Thus, although compound 11 could
exist as a mixture of optical isomers of the types a and b,
it exists predominantly as a single degenerate rotaꢀ
mer 11a. The content of the other rotamer (11b) is
below the experimental detection limit. Indeed, the
experimental spectrum exhibits a single ν(OH) band at
7a—d were –2.62, –2.51, –3.86, and –3.87 kcal mol–1
,
respectively. Thus, the rotamer percentages (g7а,s = 72.0%,
g7b,s = 28.50%, g7c,s = 4•10–6%, and g7d,s = 2•10–7%) for
a cyclohexane solution differ from those for the gas phase
by 1—3%. Apparently, transition from the gas to cycloꢀ
hexane solution would affect the percentages of rotamers
of other compounds studied to the same extent as those of
compound 7.
Thus, we carried out the conformational analysis of
compounds 6—11 and estimated the statistical weights of
the rotamers formed upon internal rotation of the βꢀhydrꢀ
oxy group and the alkenyl substituent at C(3) by quantum
chemistry methods. Based on the results, an interpretaꢀ
tion of the splitting of the experimentally observed ν(OH)
bands was proposed.
3378 cm–1
.
The relative energies of the rotamers of the comꢀ
pounds studied (see above) show that only rotamers b can
occur in the gas phase in noticeable amounts apart from
the major rotamers 6a—8a and 10a. At room temperaꢀ
ture, the populations of the vibrational levels with enerꢀ
gies exceeding the zeroꢀpoint vibrational energy by at
least 5 kcal mol–1 are negligible. Hence, at the angles
0° < θOH < 90°, 0 < θC=C < 90° and 0° < θOH < 90°,
–180° < θC=C < –90° formally corresponding to
It was shown that the content of rotamers с and d
is negligible (∼10–3—10–7%) and the splitting of the
ν(OH) bands in the spectra of these compounds in
the gas phase is only due to the internal rotation of the

Rotamers of alkenylhydroxynaphthoquinones
Russ.Chem.Bull., Int.Ed., Vol. 55, No. 10, October, 2006
1735
(0.6 mmol) and MeNH2•HCl (0.6 mmol) in benzene (10 mL),
the course of the reaction being monitored by TLC. The reacꢀ
tion mixture was cooled, washed with water (3×2 mL), dried
with anhydrous Na2SO4, and concentrated. Compounds (7, 8,
and 10) were isolated by preparative TLC on plates (20×20 cm)
with a 5—40 µm loose silica gel layer (H+ꢀform) in a 3 : 1 hexꢀ
ane—acetone system.
The reaction of lawsone (9) (174 mg) with propanal gave
79 mg (48% based on reacted 9) of 2ꢀhydroxyꢀ3ꢀ(propꢀ1ꢀenyl)ꢀ
1,4ꢀnaphthoquinone (7), m.p. 127—131 °C. IR (nꢀhexane/cycloꢀ
hexane), ν/cm–1: 3390 m, 3361 m (βꢀOH); 1680 sh w, 1663 vs
(C=O); 1636 m, 1619 m (C=C). 1H NMR (CDCl3), δ: 1.99 (dd,
3 H, Me, J1 = 1.7 Hz, J2 = 6.8 Hz); 6.63 (dq, 1 H, C(1´)H, J1 =
1.7 Hz, J2 = 16.1 Hz); 7.08 (dq, 1 H, C(2´)H, J1 = 6.8 Hz, J2 =
16.1 Hz); 7.69, 7.75 (both dt, 1 H each, H(6), H(7), J1 = 1.7 Hz,
J2 = 7.5 Hz); 7.74 (s, 1 H, βꢀOH); 8.06, 8.13 (both dd, 1 H each,
H(5), H(8), J1 = 1.7 Hz, J2 = 7.5 Hz). MS, m/z (Irel (%)): 215
[M + 1]+ (18), 214 [M]+ (100), 213 (17), 199 (37), 186 (18), 171
(33), 168 (24), 158 (22).
The reaction of lawsone (9) (174 mg) with 2ꢀethylbutanal
gave 113 mg (44%) of 2ꢀhydroxyꢀ3ꢀ(2ꢀethylbutꢀ1ꢀenyl)ꢀ1,4ꢀnaphꢀ
thoquinone (8), m.p. 91—95 °C (from a hexane—acetone
mixture). IR (nꢀhexane), ν/cm–1: 3400 sh m, 3385 m (βꢀOH);
1663 vs (C=O); 1643 m, 1599 m (C=C). 1H NMR (CDCl3),
δ: 1.01, 1.16 (both t, 3 H each, Me, J = 7.6 Hz); 2.05 (q, 2 H,
CH2, J = 7.6 Hz); 2.29 (dq, 2 H, CH2, J1 = 1.4 Hz, J2 = 7.6 Hz);
5.90 (br.s, 1 H, C(1´)H); 7.46 (s, 1 H, βꢀOH); 7.69, 7.76
(both dt, 1 H each, H(6), H(7), J1 = 1.7 Hz, J2 = 7.3 Hz);
8.09, 8.12 (both dd, 1 H each, H(5), H(8), J1 = 1.7 Hz, J2 =
7.3 Hz). MS, m/z (Irel (%)): 257 [M + 1]+ (83), 256 [M]+ (90),
255 (11), 242 (29), 241 (37), 228 (17), 227 (47), 203 (14),
202 (100).
alkenyl substituent. The theoretical ratios of the statistiꢀ
cal weights of the rotamers a and b for all compounds
are similar ((2.4—2.7) : 1), which is in good agreement
with the experimental ratios of the areas under the comꢀ
ponents of the ν(OH) bands measured in nꢀhexane and
cyclohexane solutions ((1.8—2.3) : 1). For compound 7,
the effect of the nonpolar solvent (cyclohexane) on the
ratio of rotamer percentages was calculated. The solꢀ
vation effects were shown to change the relative enerꢀ
gies of the rotamers of molecule 7 by ∆Gs ≈ 0.1•∆Ggas
.
This suggests that compounds 6, 7, and 10 exist in
(cyclo)hexane solutions as mixtures of rotamers а
(65—70%) and b (35—30%).
Experimental
Ab initio calculations were carried out by the PC GAMESS
program8 with full geometry optimization and with account of
electron correlation at the secondꢀorder level of Møller—Plesset
perturbation theory (MP2) and the density functional theory
with nonlocal exchangeꢀcorrelation functional B3LYP using the
splitꢀvalence basis sets 6ꢀ31G, 6ꢀ31(d), and 6ꢀ31(d,p). The opꢀ
timization procedure was carried out to an energy gradient of
5•10–6 a.u. Å–1. For each stationary point located on the potenꢀ
tial energy surface (PES), normalꢀmode vibrational frequencies
were calculated. The absence of imaginary frequencies indiꢀ
cated that these stationary points on the PES were minima corꢀ
responding to rotamer forms. At similar energies of rotamers c
and d and low barriers to the reaction d → c (<2 kcal mol–1
compound 8), the minima were located by scanning the PES
over the θ angle. The effect of the nonpolar solvent (cycloꢀ
,
The reaction of naphthopurpurin (2,5,8ꢀtrihydroxyꢀ1,4ꢀ
naphthoquinone) (206 mg) with propanal gave 38 mg (16%) of
2,5,8ꢀtrihydroxyꢀ3ꢀ(propꢀ1ꢀenyl)ꢀ1,4ꢀnaphthoquinone (10), m.p.
160—165 °C. IR (nꢀhexane), ν/cm–1: 3400 m, 3372 m (βꢀOH);
1645 sh w, 1620 sh m, 1605 vs (C=O); 1575 m (C=C). 1H NMR
(CDCl3), δ: 2.00 (dd, 3 H, Me, J1 = 1.7 Hz, J2 = 6.8 Hz); 6.62
(dq, 1 H, C(1´)H, J1 = 1.7 Hz, J2 = 16.1 Hz); 7.08 (dq, 1 H,
C(2´)H, J1 = 6.8 Hz, J2 = 16.1 Hz); 7.19, 7.27 (both d, 1 H
each, H(6), H(7), J = 9.5 Hz); 7.79 (br.s, 1 H, βꢀOH); 11.54,
12.87 (both s, 1 H each, αꢀOH). MS, m/z (Irel (%)): 247 [M + 1]+
C=C
hexane) on the ratio of the rotamer percentages was estimated
using the PCM model.9
Melting points were measured on a Boetius apparatus and
not corrected. 1H NMR spectra were recorded on a Bruker
ACꢀ250 spectrometer (250.13 MHz) in CDCl3 (Me4Si as
the internal standard). EI mass spectra were obtained on an
LKBꢀ9000S instrument with direct inlet and an ionizing energy
of 70 eV. IR spectra were measured on a Bruker Vector 22
FTꢀIR spectrophotometer with a resolution of 2.0 cm–1 in
nꢀhexane or cyclohexane using matched cells with CaF2 winꢀ
dows, layer thickness 1.00—2.50 mm. The frequencies and areas
were measured and the contours of the βꢀhydroxy stretching
bands were deconvolved into components using OPUS/IR 02
software, version 3.0.2. The reproducibility of frequency valꢀ
ues was at least 0.5 cm–1. The solution concentrations were
5—20 mmol L–1. The reactions were monitored and the purity
of the compounds was checked by TLC on Merck 60Fꢀ254
plates in a 3 : 1 hexane—acetone mixture. Commercial 2ꢀhydrꢀ
oxyꢀ3ꢀphenylꢀ1,4ꢀnaphthoquinone (11) ("pure" grade) was used.
The synthesis and the spectroscopic characteristics of 2ꢀhydroxyꢀ
3ꢀ(3,3ꢀdimethylbutꢀ1ꢀenyl)ꢀ1,4ꢀnaphthoquinone (6) were deꢀ
scribed previously.1 Lawsone (9) was prepared by a known proꢀ
cedure.10
+
(16), 246 [M] (100), 234 (13), 231 (15).
This work was supported by the Council on Grants at
the President of the Russian Federation (Program for the
State Support of the Leading Scientific Schools of the
Russian Federation, NSh 1237.2003.3) and by the Rusꢀ
sian Foundation for Basic Research (FarꢀEastern Branch,
Project No. 06ꢀ04ꢀ96070).
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1736
Russ.Chem.Bull., Int.Ed., Vol. 55, No. 10, October, 2006
Glazunov et al.
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Received June 10, 2005;
in revised form June 13, 2006