Unexpected reaction of 3-benzoyl-4-hydroxy-1-methyl-4-phenylpiperidine with 1,2-diaminobenzene [4]

Full text of DOI:10.1007/s10593-005-0084-9

Chemistry of Heterocyclic Compounds, Vol. 40, No. 10, 2004
ANNELATION OF 3,4-DIHYDROISOQUINOLINES
BY 3-ACYL-5,5-DIMETHYLTHIOPYRAN-2,4-DIONES.
SYNTHESIS AND PROPERTIES OF 8-AZA-
17-THIA-D-HOMOGONA-12,17a-DIONES
M. V. Budnikova, O. V. Gulyakevich, T. A. Zheldakova, A. L. Mikhal'chuk,
and D. B. Rubinov
We have used annelation of 3,4-dihydroisoquinolines by 3-acyl-5,5-dimethylthiopyran-2,4-diones to
obtain the corresponding 8-aza-17-thia-D-homogonanes, which are novel representatives of
heterosteroids. We have studied the tautomerism of 3-acylthiopyran-2,4-diones using NMR
2
spectroscopy and H/D-isotope exchange. We have obtained H-isotopomers of 3-acylthiopyran-2,4-
diones.
Keywords: 8-aza-17-thia-D-homogonanes, azomethines, 3-acyl-5,5-dimethyltetrahydrothiopyran-2,4-
diones, heterosteroids, 3,4-dihydroisoquinolines, Schiff's bases, thiopyrano[3',4':5,6]pyrido[2,1-a]-
isoquinolines, annelation, [2+4] cyclocondensation.
Among heterocyclic analogs of steroids, the most well known today are the aza analogs, in particular
those exhibiting quite valuable properties as inhibitors of 5α-reductase and antiandrogens, 4-aza steroids [1, 2],
and also 8-aza steroids, which are of considerable practical and theoretical interest as low molecular weight
immunomodulators [3-5]. Studies of the structure–function relations in the 8-aza steroid series have shown [3, 5-
7] that by means of structural and functional group transformations, we can change both the direction and the
level of their immunomodulating effect. A quite promising approach to controlling the immune activity of 8-aza
steroids is to introduce additional heteroatoms into their tetracyclic ring [8]. So far 8,16-diaza- [9], 8-aza-16-oxa-
[10], 8-aza-16-thia- [11], 8,17-diaza-D-homo- [12], and 8-aza-17-oxa-D-homogonanes have been synthesized
and studied [13]. At the same time, compounds in the 8-aza-17-thia-D-homogonane series have been described
only recently [14]. With the aim of expanding the indicated series, we have studied the reaction of 3,4-
dihydroisoquinolines
1a-d
with
3-acyl-6,6-dimethylthiopyran-2,4-diones
2a,b,
obtained
from
6,6-dimethyltetrahydrothiopyran-2,4-dione (3). In this case, it was also important to clarify the effect of the
sulfur atom in the ring of the original dione 2 on the activity of the latter in the reaction with compounds 1. We
have established that when 3,4-dihydroisoquinolines 1a,b, unsubstituted in the 1 position, are boiled in ethanol
with diones 2a,b, the corresponding tetracyclic derivatives 4a-d are formed: the products of an annelation
reaction ([2+4] cyclocondensation) at the C=N bond (Scheme 1). However, we were unable to obtain products of
type 3 from 1-methyl-substituted dihydroisoquinolines 1c,d and the same diones 2a,b. The data presented
__________________________________________________________________________________________
Institute of Bioorganic Chemistry, National Academy of Sciences of Belarus, Minsk 220141; e-mail:
rubinov@ns.iboch.ac.by. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1572-1583,
October, 2004. Original article submitted July 6, 2001; revision submitted April 4, 2002.
0009-3122/04/4010-1359©2004 Springer Science+Business Media, Inc.
1359

Scheme 1
R2
O
O
1
R1
R1
R3
8
2N
3
2
7
1S
6
3
4
+
4
R2 = H
O
O
5
O
R3
R2
1a–d
11
S 17
2a,b
D
9 C
R1
R1
14
N8
R2 = Me
B
15
A
7
4
4a–d
1a,c, 4a,c R1 = H; 1b,d, 4b,d R1 = OMe; 1a,b, 4a–d R2 = H; 1 c, d R2 = Me;
2a, 4a,b R3 = H; 2b, 4c,d R3 = Me
along with the results of previous studies [8, 9, 15, 16] allow us to say that in this case, the reaction is hindered
by the 1-Me group in dihydroisoquinolines 1c,d and also by the sulfur atom and the gem-dimethyl group in the
position 6 of diones 2a,b.
In order for the described reaction to occur, which ultimately involves formation of the C(9)–C(11) and
N(8)–C(14) bonds closing the 2,3-dihydropiperidinone ring C of 8-aza-17-thia steroids 4a-d, both substrates
should be at least bifunctionalized. In azomethines 1a-d, the C=N bond is polarized, and as a result the
azomethine carbon atom, which has electrophilic properties, reacts with nucleophiles while the nucleophilic
nitrogen atom reacts with electrophiles [17]. According to modern theories, β,β'-tricarbonyl compounds, in
particular acylthiopyrandiones 2a,b, exist as a mixture of interconverting tautomeric endo(21, 22) and exo (23, 24)
enols (Scheme 2) [18, 19], for which we may expect the presence of four sets of resonance signals in the
1H NMR spectrum. However, due to the low population of individual tautomers, rapid interconversion between
them, and other factors, the actually observed number of signals is generally significantly lower. Thus in the
1H NMR spectrum of compound 2a, along with the four major signals (integrated intensity 93%), there are
additional signals at 17.06 ppm and 2.82 ppm (I = 7%) corresponding to the enol and methylene protons of the
C(5)H2 group respectively.
Scheme 2
H
R3
O
O
O
R3
O
H
S
S
O
O
22
21
H
R3
O
O
O
O
R3
O
H
S
S
O
23
24
1360

This may be either a consequence of significantly faster interconversion rates between the endo and exo
enols 21 ↔ 23 and 22 ↔ 24 than can be distinguished on the NMR time scale [18], or else the tautomers 21, 23 and
22, 24 degenerate to betaine chelate complexes 25 and 26 due to 1,5(O,O')-tunneling proton transfer [20].
According to the data in [21], the indicated major signals are assigned to the complex 25 while the minor signals
are assigned to the complex 26. However, we cannot explain the nucleophilicity of the acyl group in the
acylthiopyran diones 2a,b within such a theory [18].
Scheme 3
+
R3
H
–
O
O
O
O
R3
O
H
S
S
–
+
O
25
26
Azomethines 1a-d are bases [22], while the β,β'-tricarbonyl compounds 2a,b are acids [23].
Consequently, the initial event in their reaction is formation of the salt 5.
R2
O
O
O
R3
R1
R1
_
+
S
NH
.
An
Cat
5
The mesomeric azomethine cation 5Cat, as was shown earlier in [15], exists as an equilibrium mixture
of immonium and enammonium tautomers. The acylthiopyrandione anion 5An is also mesomeric, and
hypothetically can exist as a heptad mesomer 5An1, pentad mesomers 5An2-5An4, or triad mesomers
5An5-5An8.
R3
O
O
O
O
O
O
O
O
O
O
_
R3
_
R3
R3
_
S
_
S
O
S
S
O
5An4
5An3
5An1
5An2
R3
O
O
_
R3
O
O
O
_
O
S
R3
R3
O
S
S
_
O
O
S
_
O
O
5An8
O
5An7
5An5
5An6
1361

Due to structural (planarity) and conformational factors, the mesomeric anions 5An2, 5An5, and 5An8,
which permit free rotation of the acyl side chain, probably have the highest populations in this series. An isotope
exchange study for acetylthiopyrandione 2a in CDCl3 and Py-d5 in the presence of D2O at 20°C showed that
under neutral conditions (CDCl3), H/D isotope exchange occurs only for the chelated proton of the enol, while
under basic conditions (Py-d5) such exchange also occurs for the protons of the methyl (methylene) group of the
acyl side chain and the methylene group C(5)H2. This suggests that for anions 5, as for anions of
2-acylcycloalkane-1,3-diones [15, 24, 25] and anions of 3-acylthiotetronic acids [16], a tautomeric equilibrium is
established between the forms [5An2, 5An5-5An8] and [5An9-5An12], where both the α' protons of the acyl
substituents and the protons of the C(5)H2 groups are involved in H/D isotope exchange (Scheme 4). The
physicochemical characteristics (1H NMR, 13C NMR, and mass spectra) of the 2H-isotopomers 6a,b obtained are
given in the experimental section.
1
According to H NMR data, as a result of H/D isotope exchange for the acylthiopyrandiones 2a,b in
Py-d5 (D2O) solutions, H/D isotope exchange also occurs for the chelated enol proton, which during separation
of the isotopomers is regenerated due to D/H exchange with atmospheric moisture. As a result, we cannot obtain
isotopomers with a chelated deuterium isotope under the described experimental conditions. Analysis of the
physicochemical characteristics of 2H isotopomers 6a,b suggests that their isotopic frequency is ~90%.
Scheme 4
R3
α
O
OH
O
'
R3
α
α
5An8
_
_
O
H
S
S
α'
O
O
5An10
5An9
5An7
5An6
R3
R3
α
O
'
α
O
'
_
α
α
O
S
_
O
H
S
5An2
5An5
H
O
O
5An11
5An12
O
O
Py-d5
D2O
R3
2a,b
S
D
D
OH
D
D
6a,b
In light of these data and the theories, we can understand the mechanism for the appearance of
nucleophilicity in the α' position of the acylthiopyrandiones 2a,b, and the electrophilicity of the C(4) atom in the
tautomers 5An2, 5An5-5An12 is obvious as a consequence of polarization and alternation effects. Considering the
above discussion, the mechanism of the reaction of annelation of 3,4-dihydroisoquinolines 1a-d by
acylthiopyrandiones 2a,b can be represented by Scheme 5.
1362

Scheme 5
1
2
+
5
OH
OH
O
O
_
δ +
S
4a–d
+
O
–H2O
S
+
N
NH
OH
7
TS
The proposed mechanism, in contrast to what has been discussed earlier in [9, 10, 12] and in accordance
with the studies in [11], assumes concerted formation of the C–C and C=N bonds, closing the dihydro-γ-
pyridinone ring C of product 4 via a six-membered transition state TS. The hypothetical alcohol 6 is either
metastable and dehydrated to form the end product under the reaction conditions, or else it is generally not
formed as an intermediate but rather the conversion 5 → 3a-d occurs with elimination of a water molecule
directly during formation of the pyridone ring C. Considering the data in [26], the second route is preferred.
The composition and structure of the synthesized compounds 2a,b and 4a-d are supported by elemental
analysis data and physicochemical studies. Thus in the mass spectra of azathia steroids 4b-d, there are
characteristic sets of signals corresponding to radical molecular ions with mass numbers from [M+2] to [M-2],
and also split signals (typical od sulfur-containing compounds) that involve the sulfur atom of the radical ions
formed upon fragmentation of the molecular ions.
In the IR spectra of diones 2a,b there are strong (~80-90%) broadened and asymmetric absorption bands
at ~1630, ~1570, and ~1470 cm-1 that are due to vibrations of the enolized β,β'-tricarbonyl moiety [19]. The
bands at ~1630 cm-1 have quite extended high-frequency slopes going into the ~1800 cm-1 region, suggesting
that they have a complex composition. We may assume that they include absorption bands for symmetric and
asymmetric stretching, bending and other vibrations of the C=O groups of the β,β'-tricarbonyl moiety. The bands
at ~1570 can be assigned to vibrations of the C=C bonds, while the intense and asymmetric absorption bands in
the 1500-1300 cm-1 region can be assigned to bending vibrations of the C–H bonds in the methylene and methyl
groups adjacent to the β,β'-tricarbonyl moiety. A distinguishing feature of the IR spectra of derivatives 2a,b is
the presence of intense absorption bands in the 870 cm-1 region, probably due to stretching vibrations of the C–S
bonds.
For the IR spectra of derivatives 4a-d, characteristic features are the strong broadened and asymmetric
absorption bands at ~1680 cm-1, which obviously include absorption bands for stretching vibrations of the
CO and C(O)S groups, and bands at ~1530 cm-1 due to stretching vibrations of the C=C bond of the enolized
β,β'-tricarbonyl moiety [27]. Intense absorption bands in the 1500-1300 cm-1 region probably belong to bending
vibrations of the C–H bonds of the methylene groups, while the bands in the 800-700 cm-1 region probably
belong to vibrations of the C–N bond.
In contrast to the cycloalkane-1,3-diones in [19], in the electronic absorption spectra of 3-acylthiopyran-
2,4-diones 2a,b we observe three absorption bands, where two long-wavelength absorption bands (240-320 nm)
have well-resolved maxima and the short-wavelength absorption band (210-240 nm) has a pronounced
absorption maximum in the case of derivative 2a while in the case of derivative 2b it appears as a faint shoulder
on the high-frequency slope of the spectral line. The refined values for the absorption maxima and minima for
diones 2a,b (obtained by taking the derivatives of the experimental spectral lines) are: for acetylthiopyrandione
2a, λmax 225, 255, and 285 nm; λmin 207.7, 240, 269.6, and 303.1 nm; for propionylthiopyrandione 2b,
λmax 226.2, 255.4, 285.4, and 418.9 nm; λmin 210.4, 242.3, 270, 303.9, 404.6, and 440 nm. While the numerical
values for the two intense (log ε > 4) long-wavelength absorption bands correlate well with the absorption bands
1363

observed for alicyclic β,β'-tricarbonyl compounds in [19] and consequently can be assigned to π → π* electronic
transitions in the β,β'-tricarbonyl moiety, the short-wavelength absorption band may be due to the sulfur atom
present in the structure of these compounds and probably can be assigned to electronic transitions in the
thiolactone group. In addition to the absorption bands discussed above, for compound 2b we can observe very
broad (~60-100 nm) low-intensity absorption bands (ε < 100) in the long-wavelength region of the spectrum that
are due to n → π* electronic transitions.
In the electronic absorption spectra of azathia-D-homogonanes 4a,c, there are two intense absorption
bands (log ε > 4) at ~270 nm and ~315 nm that are typical of compounds containing an α-acyl-β-
aminovinylcarbonyl (AAVC) group N(8)–C(14)=C(13)(–C(12)=O)–C(17/17a)=O [5, 11, 12]. In the spectra of
derivatives 4b,d, along with what has been indicated, there are also asymmetric absorption bands in the ~230 nm
region (of about the same intensity), probably due to electronic transitions of the methoxy-substituted aromatic
ring A [5, 12, 13] and the thiolactone moiety. Evidence in favor of such a conclusion is the fact that the intensity
of absorption bands due to only the methoxy-substituted aromatic ring A is generally significantly lower [5, 12,
13].
1
The NMR data were the most informative for the structural studies. Thus in the H NMR spectra of
compounds 4a-d, there are resonance signals from all the protons of the proposed structures, with a characteristic
pattern of spin–spin couplings revealed using the double resonance method. The position of the sulfur atom in
products 4 was established based on analysis of long-range spin–spin couplings, showing that for all the
indicated compounds, we observe a direct and a reverse NOE (nuclear Overhauser effect) for protons in the
positions 7 and 15, which clearly confirms position 15 for the methylene unit and accordingly position 17 for the
sulfur atom.
The series of homogonane diones 4a-d obtained also provided the opportunity to observe and study the
individual and combined effect on the spectral characteristics of these compounds from the methoxy substituents
on the aromatic ring A and the methyl group on the pyridine ring C. The effect of the methoxy group on the
benzyl proton H-9 is worth noting: it is expressed in a 20-40 Hz upfield shift of the signal from the latter (diones
4b,d). It may be due either to a hyperconjugation effect [17] or to stereoelectronic interactions between the
indicated proton and the π-electron cloud of ring A through space. We can easily track the effect of the 11-CH3
group from the downfield shift we see in all cases for the signal from the equatorial proton H-7. This effect can
be explained by perturbation of the planarity of the aminovinyldicarbonyl moiety. The remaining 1H signals for
compounds 4a-d are found in regions typical for spectra of 8-aza-D-homogonanes [19, 21, 26].
13
The most pronounced differences between the homogonane diones 4a-d are observed in their C NMR
spectra. These differences are connected not only with the appearance of additional signals as we go from the
unsubstituted dione 4a to the 2,3-dimethoxy or the 11-methyl derivatives 4b-d, but also with different positions
for some of the 13C atoms common to all the structures. Thus introducing OMe electron-donor substituents onto
the aromatic ring A causes quite obvious changes in the multiplicity and position of the signals for the 13C atoms
forming it, while substitution of the proton in the 11-CH2 group by a methyl substituent leads to a change in the
13
multiplicity and position of the
C
(11)
signal. However, the shifts of signals for nuclei far away from the
positions where structural changes occur are more meaningful for studying and understanding the
stereoelectronic changes in the molecules of the considered series of compounds. Thus the 11-methyl derivatives
13
13
13
4c,d differ from their 11-unsubstituted analogs 4a,b in the signals for the C(9), C(7),
C
(13)
atoms that are
13
shifted downfield by ~4.0 ppm, 1.0 ppm, and 1.5 ppm respectively, and also in the signal for the
C
(12)
atom,
which is found ~3 ppm upfield. These shifts are certainly connected with differences in the electronic
environment of the indicated atoms, and those differences in turn are connected with a change in the planarity of
the AAVC moiety. The change in the planarity of the AAVC moiety when a methyl group is introduced into the
position 11 may be explained by stereoelectronic effects involving interaction of the group with the π-electrons
of the aromatic ring A. This conclusion is quite consistent with X-ray diffraction data for 8-aza steroids [28] and
1364

the results of examination of Dreiding models for compounds 4a-d, which shows that due to bending of the
molecular frameworks at the N(8)–C(9) bond, the 11-Me group is found in a region of anisotropy of the π-electron
cloud of ring A.
Thus as a result of our studies we have established that reaction of 3,4-dihydroisoquinolines 1a,b with
acylthiopyrandiones 2a,b leads to the previously unknown 8-aza-17-thia-D-homogona-12,17a-diones 4a-d.
Products of annelation with an angular 9-Me group are not formed from 3,4-dihydroisoquinolines 1c,d and
acylthiopyrandiones 2a,b; the reaction mixtures become tarry and the original substrates cannot be recovered.
Attempts to obtain salts 5 from 3,4-dihydroisoquinolines 1c,d and acylthiopyrandiones 2a,b remained
unsuccessful, which is probably connected with the lability of the latter. We have shown that anions of
acylthiopyrandiones 5An exist as an equilibrium mixture of "enol–anion tautomers" 5An9-5An12, where the
tautomerism involves the hydrogen atoms of the methylene (methyl) groups adjacent to the β,β'-tricarbonyl
moiety. From acylthiopyrandiones 2a,b, we obtained 2H-isotopomers 6a,b, which are of interest for
physicochemical and biological studies.
EXPERIMENTAL
The IR spectra were obtained on a UR-20 in KBr disks. The UV spectra were taken on a Specord M-400
spectrophotometer in ethanol. The derivatives of the experimental spectral curves were taken using the built-in
software of the instrument. The mass spectra of derivatives 2a,b and their isotopomers 6a,b were measured on
an HP 5890/5972 GC/MS chromatograph/mass spectrometer (quartz capillary column HP 5MS 30 m × 0.25 mm
× 0.25 µm; carrier gas, helium, 0.7-1 µl/min; vaporizer temperature, 250°C; temperature program 40-300°C,
6°C/min). The mass spectra of the azathia steroids 4b-d were taken on a high-resolution MicroMass MasSpec
mass spectrometer with direct injection of the sample and electron ionizing energy 70 eV. The 1H and 13C NMR
spectra were obtained on a Bruker AC-200 (1H, 200 MHz and 13C, 50 MHz) and a Bruker DRX-500 (1H,
500 MHz and 13C, 125 MHz) rf spectrometer, internal standard TMS.
The course of the reactions was monitored using TLC on Silufol UV-254 plates, eluent 9:1 chloroform–
methanol. The melting points were determined on a Boetius heating stage.
The 3,4-dihydroisoquinolines 1a-d used in this work were obtained by cyclodehydration of the
corresponding phenethylamides when treated with PPA (azomethines 1a,b) or phosphorus oxychloride
(azomethines 1c,d) under Bischler–Napieralski reaction conditions [29]. 3-Acylthiopyran-2,4-diones 2a,b were
obtained by acylation of thiopyrandione 3 [30] by acetyl and propionyl chlorides in the presence of pyridine,
followed by Claisen–Haase O,C-isomerization [29] of the enol acylates formed as intermediates by treatment
with 4-dimethylaminopyridine [31]. Since 3-acylthiopyran-3,4-diones 2a,b have been described only in patent
literature [31], where there are no details given for the synthesis and their physicochemical characteristics are not
indicated, we considered it advisable to give the general procedure for obtaining these compounds and data from
physical and chemical investigation methods.
3-Acyl-6,6-dimethyltetrahydro-2H-thiopyran-2,4-diones (2a,b) (General Procedure). Dry pyridine
(0.97 ml, 12 mmol) and the corresponding acid chloride (11 mmol) were added while stirring to thiopyrandione
3 (1.58 g, 10 mmol) in dry toluene (40 ml). The reaction mixture was stirred for 1 h (monitored by TLC,
visualized with an iron chloride solution). Then the reaction mixture was washed with a 1% HCl solution, water,
and a Na2CO3 solution; then it was dried with Na2SO4 and filtered. Dimethylaminopyridine (0.25 g, 2 mmol) was
added to the filtrate; the mixture was stirred while protected from moisture for 6-8 h (monitored by TLC). The
reaction mixture was extracted with a 10% NaOH solution until the β-triketone 2 was completely recovered
(extract 1). Extract 1 was acidified with a 10% HCl solution and extracted with chloroform (4 × 20 ml,
extracts 2). The combined extracts 2 were dried with Na2SO4 and then filtered. The filtrate was evaporated down
on a rotary evaporator and the residue was crystallized from ether.
1365

3-Acetyl-6,6-dimethyltetrahydro-2H-thiopyran-2,4-dione (2a). Dione 2a (1.32 g) was obtained as
cream-colored crystals from thiopyrandione 3 (1.58 g, 10 mmol) [30] and acetyl chloride (0.78 ml, 11 mmol).
Yield 66%; mp 100°C (ether). IR spectrum, ν, cm-1: 3450, 1630, 1560, 1545, 1450, 1420, 1395, 1370, 1325,
1295, 1260, 1240, 1205, 1160, 1130, 1115, 1045, 1030, 985, 935, 880. UV spectrum, λmax, nm (lg ε): 229.6
(4.02), 256.6 (4.05), 280.4 (4.07); λmin, nm (log ε): 240 (4.00), 267.3 (4.03). 1H NMR spectrum (CDCl3), δ, ppm
(J, Hz): 1.50 (6H, s, 6-CH3); 2.58 (3H, s, 8-CH3); 2.96 (2H, s, 2H-5); 18.40 (1H, s, OH). 13C NMR spectrum (Py-
d5), δ, ppm: 27.616 (C-8); 29.348 (6-CH3); 42.988 (C-6); 49.791 (C-5); 112.885 (C-3); 189.095 (C-2); 197.226
(C-4); 199.762 (C-7). Mass spectrum, m/z (Irel, %): 202.05 [M+2]+· (5.8); 201.05 [M+1]+· (11.3); 200.05 [M]+·
(100); 185.05 [M-15]+· (15.3); 172.10 (12.1); 167.10 (15.4); 158.05 (3.2); 157.05 (20.0); 153.05 (5.1); 151.05
(6.6); 145.05 (13.5); 144.05 (13.1); 126.00 (10.0); 125.10 (4.3); 115.95 (9.1); 110.95 (7.1); 100.95 (9.0); 99.00
(3.1); 98.00 (50.9); 89.00 (5.9); 24.65 (87.9); 85.00 (19.9); 84.00 (74.3); 83.00 (63.8); 76.95 (3.2); 74.95 (13.9);
73.95 (9.5); 70.95 (3.0); 69.95 (11.5); 68.95 (30.4); 66.95 (5.6); 60.95 (3.3); 58.90 (20.2); 57.90 (3.2); 57.00
(6.6); 56.00 (9.7); 55.00 (21.2); 53.00 (7.2); 45.00 (7.5); 44.00 (5.8); 43.00 (77.6); 42.10 (5.0). Found, %: C
53.79, 53.87; H 5.92, 5.85; S 16.12, 15.84. C9H12O3S. Calculated, %: C 53.98; H 6.04; S 16.01. M 200.26.
6,6-Dimethyl-3-propionyltetrahydro-2H-thiopyran-2,4-dione (2b). Propionylthiopyrandione 2b (1.28
g) was obtained as colorless crystals from thiopyrandione 3 (1.58 g, 10 mmol) [30] and propionyl chloride (0.96
ml, 11 mmol). Yield 60%; mp 53°C (ether). IR spectrum, ν, cm-1: 3450, 1630, 1580, 1560, 1450, 1420, 1395,
1370, 1310, 1270, 1260, 1140, 1130, 1085, 985, 940, 870. UV spectrum, λmax, nm (log ε): 257.7 (4.09), 280.8
(4.10), 413.5 (2.51); λmin, nm (log ε): 205 (3.56), 270 (4.07), 365 (2.38). 1H NMR spectrum (CDCl3), δ, ppm (J,
Hz): 1.18 (3H, t, J = 7.0, 9-CH3); 1.50 (6H, s, two 6-CH3); 2.90 (2H, s, two H-5); 3.04 (2H, q, J = 7.0, two H-8);
18.54 (1H, s, OH). 13C NMR spectrum (Py-d5), δ, ppm: 8.852 (C(9)); 29.301 (6-CH3); 33.582 (C(8)); 43.043 (C(6));
49.391 (C(5)); 112.415 (C(3)); 188.982 (C(2)); 196.402 (C(4)); 204.084 (C(7)). Mass spectrum, m/z (Irel, %): 216.10
[M+2]+· (5.77); 215.10 [M+1]+· (12.2); 214.10 [M]+· (98.9); 199.05 [M-15]+· (4.2); 186.05 (4.2); 185.05 (35.6);
182.10 (3.1); 181.10 (28.2); 180.10 (8.0); 172.00 (5.6); 171.10 (11.6); 165.10 (25.7); 158.95 (4.6); 157.95 (6.1);
156.95 (3.6); 153.05 (3.6); 140.00 (7.6); 138.00 (3.2); 130.00 (16.5); 125.00 (9.2); 124.00 (3.9); 116.95 (4.7);
111.95 (19.3); 110.95 (6.4); 101.95 (17.3); 100.95 (6.8); 99.00 (8.9); 98.00 (23.6); 97.00 (14.8); 89.00 (5.9);
86.90 (3.2); 83.00 (100); 76.95 (3.8); 74.95 (14.4); 73.95 (7.7); 70.95 (4.1); 69.95 (5.4); 68.95 (51.6); 66.95
(3.6); 60.95 (5.4); 58.90 (18.1); 57.90 (4.8); 57.00 (67.5); 56.00 (9.5); 55.00 (27.4); 53.00 (8.8); 51.00 (3.1);
45.00 (7.3); 44.00 (5.3); 43.00 (11.8); 42.10 (4.7). Found, %: C 55.87, 55.93; H 6.53, 6.46; S 14.82, 15.05.
C10H14O3S. Calculated, %: C 56.05; H 6.59; S 14.96. M 214.28.
rac-16,16-Dimethyl-8-aza-17-thia-D-homogona-1,3,5(10),13-tetraene-12,17a-diones
(General
Procedure). An equimolar mixture of 3,4-dihydroisoquinoline 1a-d and acylthiopyrandione 2a,b in an ~3-5-fold
volume of alcohol was boiled under a stream of argon; the course of the reaction was followed using TLC. It
took 15-24 h to complete the process. Then the reaction mixture was evaporated down to one-third of the
original volume and held at 0 to +5°C. The separated product 4 was filtered out and recrystallized from alcohol.
rac-16,16-Dimethyl-8-aza-17-thia-D-homogona-1,3,5(10),13-tetraene-12,17a-dione (4a). Product 4a
(0.21 g) was obtained as colorless crystals from isoquinoline 1a (0.13 g, 1 mmol) and dione 2a (0.2 g, 1 mmol).
Yield 67%; mp 227-230°C (alcohol). IR spectrum, ν, cm-1: 3100-2830, 1680, 1620, 1590, 1530, 1500, 1480,
1445, 1420, 1380, 1320, 1300, 1270, 1250, 1230, 1200, 1160, 1150, 1120, 1070, 1040, 1010, 985, 955, 905,
890, 880, 840, 800, 760. UV spectrum, λmax, nm (log ε): 273.80 (4.25), 315.30 (4.35); λmin, nm (log ε): 236.45
1
(3.77), 288.80 (4.06). H NMR spectrum (CDCl3), δ, ppm (J, Hz): 1.48 (3H, s, 16-CH3); 1.52 (3H, s, 16-CH3);
2.70 (1H, dd, J1 = 15.0, J2 = 15.5, 11-HB); 2.90 (1H, dd, J1 = 15.5, J2 = 4.0, 11-HA); 2.98 (2H, s, two 15-H); 3.02
(2H, m, two 6-H); 3.50 (1H, m, 7-Ha); 4.20 (1H, tt, J1 = 13.0, J2,3 = 4.0, 7-He); 5.94 (1H, dd, J = 15.0, J = 4.0,
9-HX); 7.20 (4H, m, 1-, 2-, 3-, 4-H). 13C NMR spectrum (CDCl3), δ, ppm: 29.40 (16-CH3), 29.62 (16-CH3),
30.14 (C(6)), 42.79 (C(11)), 43.30 (C(16)), 45.94 (C(15)), 46.68 (C(7)), 57.59 (C(9)), 107.98 (C(13)), 127.03 (C(4)),
1366

128.33 (C(1)), 128.46 (C(3)), 129.04 (C(2)), 132.06 (C(10)), 136.11 (C(5)), 170.55 (C(14)), 189.89 (C(17a)), 194.49
(C(12)). Found, %: C 69.09, 68.92; H 6.05, 6.20; N 4.38, 4.34; S 10.12, 10.36. C18H19NO2S. Calculated, %:
C 68.98; H 6.11, N 4.47; S 10.23. M 313.40.
rac-2,3-Dimethoxy-16,16-dimethyl-8-aza-17-thia-D-homogona-1,3,5(10),13-tetraene-12,17a-dione
(4b). Product 4b (0.264 g) as colorless crystals was obtained from isoquinoline 1b (0.19 g, 1 mmol) and dione
2a (0.2 g, 1 mmol). Yield 70.7%; mp 259-261°C (alcohol). IR spectrum, ν, cm-1: 3100-2830, 1680, 1620, 1600,
1525, 1510, 1455, 1420, 1380, 1340, 1310, 1265, 1230, 1210, 1150, 1120, 1065, 1055, 1020, 990, 960, 870,
835, 780. UV spectrum, λmax, nm (log ε): 202.4 (4.73), 230.6 (4.14), 275.00 (4.25), 315.30 (4.29); λmin, nm
1
(log ε): 225.05 (4.40), 246.75 (3.90), 292.95 (4.14). H NMR spectrum (CDCl3), δ, ppm (J, Hz): 1.48 (3H, s,
16-CH3); 1.52 (3H, s, 16-CH3); 2.65 (1H, dd, J = 15.0, J = 15.5, 11-HB); 2.86 (1H, dd, J = 15.5, J = 3.5, 11-HA);
2.89 (1H, m, 6-He); 2.96 (2H, s, two 15-H); 3.05 (1H, m, 6-Ha); 3.42 (1H, tt, J = 11, J = 3.6, 7-Ha); 3.85 (3H, s,
OCH3); 3.88 (3H, s, OCH3); 4.20 (1H, tt, J = 13, J = 4, 7-He); 4.85 (1H, dd, J = 15.1, J = 3.5, 9-HX); 6.63 (1H, s,
4-H); 6.68 (1H, s, 1-H). 13C NMR spectrum (CDCl3), δ, ppm: 29.38 (16-CH3); 29.68 (16-CH3); 29.80 (C(6));
43.31 (C(16)); 43.32 (C(11)); 45.86 (C(15)); 46.72 (C(7)); 56.30 (3-OCH3); 56.46 (2-OCH3); 57.85 (C(9)); 107.95
(C(13)); 110.07 (C(4)); 111.95 (C(1)); 124.83 (C(10)); 128.40 (C(5)); 149.40 (C(3)); 149.79 (C(2)); 170.38 (C(14));
189.79 (C(17a)); 194.72 (C(12)). Mass spectrum, m/z (Irel, %): 375 [M+2]+· (8.4), 374 [M+1]+· (25.1), 373 [M]+·
(100); [M-1]+· 372 (13.3), 359 (7.2), 358 [M-15]+· (27.4), 346 (9.1), 345 (40.8), 341 (12.5), 340 (45.5), 331
(12.5), 330 (33.0), 313 (8.5), 312 (16.5), 302 (11.5), 299 (14.8), 298 (39.5), 284 (12.3), 271 (18.8), 270 (24.5),
256 (6.3), 243 (17.9), 242 (16.5), 204 (8.3), 192 (8.1), 191 (13.7), 190 (30.0), 188 (10.5), 177 (8.1), 176 (12.3),
146 (8.5), 115 (5.0), 107 (7.5), 91 (5.5), 77 (9.5), 59 (8.5). Found: m/z 373.133661 [M]+· C20H23NO4S.
Calculated: M 373.134780.
rac-11,16,16-Trimethyl-8-aza-17-thia-D-homogona-1,3,5(10),13-tetraene-12,17a-dione
(4c).
Product 4c (0.25 g) was obtained as colorless crystals from isoquinoline 1a (0.13 g, 1 mmol) and dione 2b
(0.21 g, 1 mmol). Yield 77%; mp 223-225°C (alcohol). IR spectrum, ν, cm-1: 3100-2830, 1680, 1600, 1530,
1505, 1475, 1450, 1380, 1360, 1320, 1300, 1270, 1265, 1240, 1200, 1150, 1130, 1110, 1060, 1030, 1010, 990,
970, 940, 885, 835, 800, 760. UV spectrum, λmax, nm (log ε): 273.25 (4.26), 315.00 (3.36); λmin nm (log ε):
1
237.35 (3.82), 288.55 (4.06). H NMR spectrum (CDCl3), δ, ppm (J, Hz): 0.82 (3H, d, 11-CH3); 1.48 (3H, s,
16-CH3); 1.52 (3H, s, 16-CH3); 2.68 (1H, m, 11-H); 3.02 (4H, m, two H-15, two 6-H); 3.40 (1H, m, 7-Ha); 4.32
(1H, m, 7-He); 5.04 (1H, d, J = 2.7, 9-Ha); 7.26 (4H, m, 1-, 2-, 3-, 4-H). 13C NMR spectrum (CDCl3), δ, ppm:
9.46 (11-CH3), 29.39 (16-CH3), 29.63 (16-CH3), 30.09 (C(6)), 43.24 (C(16)), 46.79 (C(15)), 47.61 (C(7)), 49.51
(C(11)), 61.68 (C(9)), 109.46 (C(13)), 125.53 (C(3)), 126.78 (C(4)), 129.29 (C(1)), 129.10 (C(2)), 134.76 (C(10)), 135.24
(C(5)), 171.40 (C(14)), 188.79 (C(17a)), 189.94 (C(12)). Mass spectrum, m/z (Irel, %): 329 [M+2]+· (9.8), 328 [M+1]+·
(31.9), 327 [M]+ (100), 326 [M-1]+· (9.0), 325 [M-2]+· (5.5), 313 (11.6), 312 [M-15]+· (41.5), 299 (19.5), 298
(6.0), 296 (6.5), 295 (12.0), 294 (48.9), 285 (9.5), 284 (24.7), 278 (7.0), 267 (6.1), 266 (12.0), 253 (11.5), 252
(29.1), 238 (8.5), 225 (7.8), 224 (12.6), 209 (5.8), 210 (7.6), 197 (13.1), 196 (20.5), 182 (10.2), 181 (8.6), 132
(26.5), 131 (10.1), 130 (35.9), 129 (8.9), 128 (12), 117 (11.9), 116 (8.6), 115 (15.8), 108 (9.8), 106 (5.5), 105
(6.4), 103 (7.4), 91 (9.2), 77 (12.8), 59 (8.5). Found: m/z 327.129547 [M]+· C19H21NO2S. Calculated:
M 327.129301.
rac-2,3-Dimethoxy-11,16,16-trimethyl-8-aza-17-thia-D-homogona-1,3,5(10),13-tetraene-12,17a-dione
(4d). Product 4c (0.29 g) as colorless crystals was obtained from isoquinoline 1b (0.19 g, 1 mmol) and dione 2b
(0.21 g, 1 mmol). Yield 72%; mp 268-270°C (alcohol). IR spectrum, ν, cm-1: 3100-2830, 1685, 1660, 1620,
1600, 1520, 1460, 1450, 1380, 1360, 1340, 1320, 1310, 1270, 1235, 1210, 1155, 1130, 1110, 1085, 1040, 1025,
995, 940, 880, 825, 795. UV spectrum, λmax, nm (log ε): 202.35 (4.55), 231.45 (4.09), 275.00 (4.18), 314.40
(4.22); λmin, nm (log ε): 222.05 (4.05), 247.05 (3.85), 290.00 (4.09). 1H NMR spectrum (CDCl3), δ, ppm (J, Hz):
0.8 (3H, d, J = 7, 11-CH3); 1.47 (3H, s, 16-CH3); 1.51 (3H, s, 16-CH3); 2.62 (1H, m, 11-Ha); 2.86 (1H, dd,
J1 = 15.6, J2 = 2.8, 11-Ha); 2.96 (4H, m, two 6-H, two 15-H); 3.34 (1H, ddd, J1,2 = 12.4, J3 = 2.3, 7-Ha); 3.85
(3H, s, OCH3); 3.89 (3H, s, OCH3); 4.30 (1H, tt, J1 = 12.4, J2,3 = 2.3, 7-He);4.96 (1H, d, 9-Ha); 6.58 (1H, s, 4-H);
1367

6.67 (1H, s, 1-H). 13C NMR spectrum (CDCl3), δ, ppm: 9.51 (11-CH3), 29.41 (16-CH3), 29.59 (16-CH3), 29.75
(C(6)), 43.36 (C(16)), 45.02 (C(15)), 47.52 (C(11)), 47.68 (C(7)), 56.51 (2-OCH3), 56.34 (3-OCH3), 61.87 (C(9), 109.54
(C(13)), 110.29 (C(4)), 112.32 (C(1)), 126.78 (C(10)), 127.44 (C(5)), 149.57 (C(2)), 149.57 (C(3)), 174.41 (C(14)),
189.18 (C(17a)), 190.41 (C(12)). Mass spectrum, m/z (Irel, %): 390 [M+2]+· (8.0), 388 [M+1]+· (26.5), 387 [M]+·
(100), 386 [M-1]+· (13.0), 373 [M-2]+· (6.8), 372 [M-15]+· (26.8), 359 (8.7), 355 (7.2), 354 (26.5), 350 (8.5), 349
(24.5), 326 (7.2), 312 (11.5), 285 (6.0), 284 (9.0), 270 (5.1) 266 (5.0), 242 (6.2), 192 (13.1), 191 (24.8), 190
(18.8), 177 (8.5), 176 (13.0), 107 (5.8). Found: m/z 387.147285 [M]+· C21H25NO4S. Calculated: M 387.147058.
1
[5,5,8,8,8-(5)2H]-3-Acetyl-6,6-dimethyltetrahydro-2H-thiopyran-2,4-dione (6a). H NMR spectrum
(CDCl3), δ, ppm (J, Hz): 1.50 (6H, s, 6-CH3); 18.6 (1H, s, OH). 13C NMR spectrum (CDCl3), δ, ppm: 29.348
(two CH3); 42.988 (C(6)); 112.885 (C(3)); 189.095 (C(2)); 197.226 (C(4)); 199.762 (C(7)). Mass spectrum,
m/z (Irel,%): 206.20 [M+1]+· (13.2); 295.20 [M]+· (80.9); 204.20 [M-1]+· (64.8); 203.15 (16.6); 190.05 [M-15]+·
(10.1); 189.05 (8.4); 177.10 (8.9); 176.10 (7.1); 171.10 (8.5); 179.10 (7.8); 162.05 (16.3); 161.05 (13.6); 148.05
(14.02); 147.05 (18.5); 146.05 (9.0); 131.00 (7.4); 130.00 (7.4); 118.95 (9.5); 117.95 (5.3); 113.95 (5.4); 103.05
(44.4); 102.05 (41.3); 101.05 (12.6); 92.00 (5.1); 91.00 (30.1); 90.00 (15.9); 89.00 (9.6); 88.00 (18.6); 87.00
(82.4); 86.00 (44.6); 85.00 (18.9); 84.00 (84.3); 83.00 (17.4); 74.95 (30.8); 73.95 (23.1); 72.95 (6.1); 69.95
(16.4); 68.95 (42.2); 67.95 (5.7); 60.95 (5.2); 59.95 (6.0); 58.90 (39.5); 58.00 (20.2); 57.00 (21.3); 56.00 (14.1);
55.00 (5.6); 54.00 (6.0); 47.00 (5.1); 46.00 (100); 45.00 (69.5); 44.00 (23.4); 43.00 (14.4); 42.00 (12.7).
[5,5,8,8-(4)2H]-6,6-Dimethyl-3-propionyltetrahydro-2H-thiopyran-2,4-dione (6b). 1H NMR
spectrum (CDCl3), δ, ppm (J, Hz): 1.18 (3H, s, 9-H3); 1.50 (6H, s, two 6-CH3); 18.95 (1H, s, OH). 13C NMR
spectrum (CDCl3), δ, ppm: 8.852 (C(9)); 29.301 (two 6-CH3); 43.043 (C(6)); 112.415 (C(3)); 188.982 (C(2));
196.402 (C(4)); 204.084 (C(7)). Mass spectrum, m/z (Irel, %): 219.10 [M+1]+· (13.0); 218.10 [M]+· (45.6); 217.10
[M-1]+· (37.1); 216.10 (7.0); 188.05 (11.6); 187.05 (22.2); 186.05 (6.4); 184.15 (12.5); 183.10 (11.6); 182.10
(5.6); 175.10 (6.5); 174.00 (8.1); 168.10 (9.3); 167.10 (12.3); 159.95 (5.8); 143.05 (5.0); 132.00 (11.7); 131.00
(10.5); 127.00 (5.7); 126.00 (6.5); 115.95 (9.5); 114.95 (14.9); 113.95 (7.7); 112.95 (6.0); 103.95 (14.3); 102.95
(15.9); 101.95 (8.4); 100.95 (10.7); 100.00 (21.3); 99.00 (24.0); 98.00 (12.5); 91.00 (7.0); 88.00 (6.2); 87.00
(11.7); 86.00 (12.3); 85.00 (24.4); 84.00 (100); 83.00 (24.80); 74.95 (22.2); 73.95 (13.5); 72.95 (5.2); 71.95
(5.1); 70.95 (8.6); 69.95 (20.4); 68.95 (82.4); 67.95 (7.7); 60.95 (8.4); 59.95 (8.2); 59.00 (88.7); 58.00 (68.8);
57.00 (33.9); 56.00 (26.5); 55.00 (12.6); 54.00 (9.2); 53.00 (7.3); 46.00 (6.0); 45.00 (20.1); 44.00 (17.7); 43.00
(24.5); 42.00 (19.8).
We would like to sincerely thank Academician Afanasii Andreevich Akhrem for his attention to the
studies conducted and useful comments in discussion of the experimental data and theoretical studies.
REFERENCES
1.
2.
3.
Li Xun, S. M. Singh, and F. Labrie, J. Med. Chem., 38, 1158 (1995).
M. Lourdusamy, J. Cote, S. Laplante, F. Labrie, and S. M. Singh, Bioorg. Med. Chem., 5, 305 (1997).
A. A. Akhrem, F. A. Lakhvich, L. G. Lis, and B. B. Kuz'mitskii, Vestsi AN BSSR, Ser. Khim. Navuk,
No. 6, 81 (1982).
4.
5.
6.
A. A. Akhrem, B. B. Kuz'mitskii, F. A. Lakhvich, V. A. Khripach, and Yu. L. Zhuravkov, in: The
Chemistry and Biology of Immunoregulators [in Russian], Zinatne, Riga (1985), p. 265.
N. A. Konoplya, O. V. Gulyakevich, A. L. Mikhal'chuk, and B. B. Kuz'mitskii, Vestsi AN Belarusi, Ser.
Khim. Navuk, No. 3, 91 (1994).
B. B. Kuz'mitskii, I. G. Dad'kov, Yu. L. Zhuravkov, N. A. Konoplya, G. S. Lyubin, A. E. Mashkovich,
V. M. Nasek, O. V. Gulyakevich, V. N. Pshenichnyi, and V. A. Khripach, Vestsi AN BSSR, Ser. Khim.
Navuk, No. 1, 64 (1989).
1368

7.
G. S. Lyubin, I. G. Dad'kov, O. V. Gulyakevich, and B. B. Kuz'mitskii, Vestsi AN BSSR, Ser. Khim.
Navuk, No. 2, 93 (1990).
8.
9.
F. A. Lakhvich, L. G. Lis, and A. A. Akhrem, Usp. Khim., 53, 1014 (1984).
V. N. Pshenichnyi, O. F. Lakhvich, and V. A. Khripach, Vestsi AN BSSR, Ser. Khim. Navuk, No. 5, 70
(1991).
10.
11.
A. A. Akhrem, F. A. Lakhvich, L. G. Lis, and V. N. Pshenichnyi, Zh. Org. Khim., 15, 1396 (1979).
M. V. Budnikova, D. B. Rubinov, L. G. Lis, and A. L. Mikhal'chuk, Mendeleev Commun., 5, 208
(1999).
12.
13.
M. von Strandtmann, M. P. Cohen, and J. Shavel, Jr., J. Org. Chem., 31, 797 (1966).
A. A. Akhrem, A. M. Moisenkov, and V. A. Krivoruchko, Izv. Akad. Nauk SSSR, Ser. Khim., 1302
(1973).
14.
15.
M. V. Budnikova, T. A. Zheldakova, D. B. Rubinov, and A. L. Mikhal'chuk, Zh. Org. Khim., 37, 306
(2001).
A. L. Mikhal'chuk, O. V. Gulyakevich, Yu. V. Shklyaev, V. S. Shklyaev, and A. A. Akhrem, Khim.
Geterotsikl. Soedin., 681 (1998).
16.
17.
M. V. Budnikova, A. L. Mikhal'chuk, and D. B. Rubinov, Khim. Geterotsikl. Soedin., 265 (2004).
G. Bekker, Introduction to the Electronic Theory of Organic Reactions [Russian translation from
German by V. M. Potapov], Mir, Moscow (1977), 658 pp.
18.
19.
20.
21.
22.
V. I. Minkin, L. P. Olekhnovich, and Yu. A. Zhdanov, Molecular Design of Tautomeric Systems
[in Russian], Izdat. Rost. Univ., Rostov (1977), 272 pp.
A. L. Mikhal'chuk, O. V. Gulyakevich, A. A. Zenyuk, A. V. Korchik, L. G. Lis, V. A. Khripach,
L. I. Ukhova, and A. A. Akhrem, Dokl. Akad. Nauk, 317, 1397 (1991).
K. H. Grellman and J. S. Stephan, in: Abstracts, 210th ACS Division of Physical Chemistry National
Meeting, Chicago, Illinois, August 20-24 (1995), Washington, D.C.
A. L. Mikhal'chuk, O. V. Gulyakevich, D. B. Rubinov, and A. A. Akhrem, Khim. Geterotsikl. Soedin.,
374 (1993).
Azomethines. Structure, Properties, and Application [in Russian], Izdat. Rost. Univ., Rostov-na-Donu
(1967), p. 293.
23.
24.
O. A. Reutov, I. P. Beletskaya, and K. P. Butin, CH Acids [in Russian], Nauka, Moscow (1980), 247 pp.
A. L. Mikhal'chuk and O. V. Gulyakevich (BY), Belarus Patent Appl. 19990626; Afitsyiny Byuleten.
Vynakhodnitstvy, Karystnyya Madeli, Pramyslovyya Uzory, No. 4, 36 (2000).
A. L. Mikhal'chuk and O. V. Gulyakevich (BY), Belarus Patent Appl. 19990627; Afitsyiny Byuleten.
Vynakhodnitstvy, Karystnyya Madeli, Pramyslovyya Uzory, No. 4, 36 (2000).
A. L. Mikhal'chuk, O. V. Gulyakevich, D. B. Rubinov, and I. L. Rubinova, Zh. Org. Khim., 34, 956
(1998).
A. A. Akhrem, N. A. Borisevich, A. A. Govorova, O. V. Gulyakevich, A. S. Lyakhov,
A. L. Mikhal'chuk, I. V. Skornyakov, and G. B. Tolstorozhev, Zh. Prirodn. Soedin., 69, 303 (2001).
O. V. Gulyakevich, I. L. Rubinova, D. B. Rubinov, A. A. Govorova, A. S. Lyakhov, and
A. L. Mikhal'chuk, Mendeleev Commun., 208 (1999).
25.
26.
27.
28.
29.
K. V. Vatsuro and G. L. Mishchenko, Name Reactions in Organic Chemistry [in Russian], Khimiya,
Moscow (1976), 528 pp.
30.
31.
K. Schweiger, Monatsh. Chem., 113, 1283 (1982).
H.-J. Wroblowsky, J. Stetter, L. Eue, R. R. Schmidt, and H.-J. Santel, Ger. Pat. 3421351; Chem. Abstr.
105:42651 (1986).
1369