Condensed isoquinolines 28. Synthesis and properties of 10a,15b-diazadibenzo[a,e]-pleiaden-11-ones

Article abstract of DOI:10.1007/s10593-008-0025-5

The reaction of 7,12-dihydro-5H-isoquino[2,3-a]quinazolin-5-ones with o-xylidene dibromide leads to 11-oxo-4bH,5H,10H,11H,16H-10a-aza-15b- azoniadibenzo[a,e]pleiadene bromides, which are converted to 11-oxo-10H,11H,16H-10a-aza-15b-azoniadibenzo[a,e]pleiadene salts upon oxidation using nitrobenzene. The reaction of these salts with benzylamine leads to 6-{2-[(benzylimino)methyl]phenyl}-7,12-dihydroisoquino[3,2-b][2] benzazepin-14(6H)-ones, which recyclize to 11-oxo-5H,10H,11H-10a-aza-15b- azoniadibenzo[a,e]pleiadene perchlorates upon the action of perchloric acid. The reactions of the 10a,15b-diazadibenzo[a,e]pleiadene salts obtained with NaBH₄ were studied and the structures of the reduction products were determined by spectral methods.

Full text of DOI:10.1007/s10593-008-0025-5

Chemistry of Heterocyclic Compounds, Vol. 44, No. 2, 2008
CONDENSED ISOQUINOLINES
28*. SYNTHESIS AND PROPERTIES
OF 10a,15b-DIAZADIBENZO[a,e]-
PLEIADEN-11-ONES
V. M. Kisil, L. M. Potikha, A. V. Turov, and V. A. Kovtunenko
The reaction of 7,12-dihydro-5H-isoquino[2,3-a]quinazolin-5-ones with o-xylidene dibromide leads to
11-oxo-4bH,5H,10H,11H,16H-10a-aza-15b-azoniadibenzo[a,e]pleiadene
bromides,
which
are
converted to 11-oxo-10H,11H,16H-10a-aza-15b-azoniadibenzo[a,e]pleiadene salts upon oxidation
using nitrobenzene. The reaction of these salts with benzylamine leads to 6-{2-[(benzylimino)methyl]-
phenyl}-7,12-dihydroisoquino[3,2-b][2]benzazepin-14(6H)-ones, which recyclize to 11-oxo-
5H,10H,11H-10a-aza-15b-azoniadibenzo[a,e]pleiadene perchlorates upon the action of perchloric acid.
The reactions of the 10a,15b-diazadibenzo[a,e]pleiadene salts obtained with NaBH4 were studied and
the structures of the reduction products were determined by spectral methods.
Keywords: 10a,15b-diazadibenzo[a,e]pleiadene, isoquino[2,3-a]quinazoline, quinazolino[3,2-b][2]-
benzazepine, borohydride reduction, oxidation.
In previous work [2], we reported that the reaction of 7,12-dihydro-5H-isoquino[2,3-a]quinazolin-5-one
(1a) with o-xylylene dibromide leads to derivative of a new heterocyclic system, 10a,15b-diazadibenzo-
[a,e]pleiadene. This system is a unique combination of three condensed heterocycles, namely, isoquinoline,
quinazoline, and benzazepine, each of which, considering the enormous amount of information on the biological
activity of their derivatives (see, for example, some recent studies [3-5]), may be seen as holding promise for
medicinal chemistry [6]. Furthermore, there is considerable evidence that polycondensed systems containing
elements of these heterocycles are found in nature and possess biological activity [7-10]. These findings have led
us to synthesize new derivatives of diazadibenzopleiadene system starting with substituted 7,12-dihydro-
5H-isoquino[2,3-a]quinazoline-5-ones and to carry out a detailed study of the chemical transformations of these
compounds. This was the subject of the present work.
We have found that, similar to 1a [2], aryl-substituted isoquinoquinazolines react with o-xylylene
dibromide to give different types of products depending on the reaction conditions. Thus, in the presence of
strong bases, the alkylation of 1b-d leads to spiro[5H-isoquino[2,3-a]quinazoline-(12H)-2'-indan]-5-ones 2b-d
in high yield.
_______
* For Communication see 27 [1].
__________________________________________________________________________________________
Taras Shevchenko Kiev National University, 01033 Kiev, Ukraine, e-mail: potikha_l@mail.ru. Translated
from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 280-292, February, 2008. Original article submitted
March 27, 2007.
214
0009-3122/08/4402-0214©2008 Springer Science+Business Media, Inc.

R1
R1
R2
R2
CH2Br
CH2Br
N
N
+
N
O
N
O
1a-d
2a-d
R1
R1
R2
–
R2
Br
1
+
12
N
N
N
O
N
O
4
6
3a-d
4a-d
a R1 = R2 = H; b R1 = Cl, R2 = H; c R1 = H, R2 = Me; d R1 = H, R2 = Br
Carrying out the reaction by fusing a mixture of equivalent amounts of the starting compounds at
110-120°C leads to 11-oxo-5,10,11,16-tetrahydro-4bH-10a-aza-15b-azoniadibenzo[a,e]pleiadene bromides 3b-d
(Table 1). Reaction products 3 were obtained in good yield and the formation of by-products was minimal. Some
difference was found in the time required for complete conversion of the starting materials: thin-layer
chromatography indicated that complete conversion for 1c (R2 = Me) was achieved in 3.5 h, while the reaction
was complete for 1b (R1 = Cl) after only 1 h. The action of Et3N on salts 3b-d leads to C(4b)-deprotonation to
give 5,10-dihydro-11,16-tetrahydro-10a,15b-diazadibenzo[a,e]pleiaden-11-ones 4b-d. The reversibility of this
transformation was established in our previous work [2] for aryl-nonsubstituted diazadibenzopleiadene 4a. The
data from the IR and 1H NMR spectra of solutions of salts 3b-d in CF3CO2D, bases 4b-d in CDCl3 (see Table 2),
and spiro compounds 2b-d in CDCl3 are in good accord, on the whole, with the data for aryl-nonsubstituted 2a,
3a, and 4a [2].
In earlier work [11], we showed that 6-methyl-5-oxo-5,6,7,12-tetrahydroisoquino[2,3-a]quinazolin-
13-ium perchlorate (5) is readily oxidized by nitrobenzene to give 6-methyl-5(6H)-oxoisoquino-
[2,3-a]quinazolin-13-ium perchlorate (6), which undergoes reversible opening of the C(12)–N(13) bond by the
action of primary amines. In particular, this reaction with benzylamine leads to 2-{2-[(benzylimino)-
methyl]benzyl}-3-methyl-4-(3H)-quinazolinone (7).
It would be logical to assume that analogous assignments would be found for
diazadibenzopleiadenes 3a-d in light of their obvious structural similarity. However, the benzazepine system
produces significant change in the reactivity of the isoquinoquinazoline fragment. Thus, the oxidation of
salts 3a-c, achieved by heating the solutions of these compounds in nitrobenzene with subsequent treatment by
perchloric acid, does not lead to the expected aromatization of the isoquinoline ring but rather to
dehydrogenation of the C(4b)–C(5) bond to give 11-oxo-10,10a,11,16-tetrahydro-10a-aza-15b-azoniadibenzo-
[a,e]pleiadene perchlorates 8a-c. Analysis of the spatial models showed that the molecules of salts 8 are
nonplanar; the azepine ring has distorted boat conformation, leading to molecular asymmetry, nonequivalence of
1
the protons of the C(10)H2 and C(16)H2 methylene groups, which are seen in the H NMR spectra as AB spin
systems with 2J = 14 and 2J = 16 Hz, respectively (Table 2).
215

TABLE 1. Physicochemical Characteristics of the Synthesized Compounds
Found, %
Calculated, %
——————
Com-
pound
Empirical
formula
Yield,
%
mp, °C*
C
H
Hal
N
2b
2c
2d
3b
С24H17СlN2O
С25H20N2O
74.85
74.90
82.30
82.39
67.09
67.14
61.81
61.89
4.40
4.45
5.47
5.53
3.90
3.99
3.86
3.90
9.22
9.21
7.29
7.28
7.70
7.69
6.54
6.53
6.01
6.01
297-299
292-294
276-278
255-258
74
61
69
73
С24H17BrN2O
С24Н18BrClN2O
18.61
18.61
17.17
17.16
7.62*2
7.61
3c
С25Н21BrN2O
С24Н18Br2N2O
С24Н17ClN2O
С25Н20N2O
67.37
67.42
56.46
56.50
74.87
74.90
82.39
82.39
67.05
67.14
64.14
64.22
59.60
59.64
64.80
64.87
82.16
82.26
74.84
74.90
82.28
82.39
81.68
81.73
75.91
75.99
64.16
64.22
81.69
81.79
4.70
4.75
3.47
3.56
4.39
4.45
5.53
5.53
3.89
3.99
3.78
3.82
3.28
3.34
4.06
4.14
5.09
5.18
4.37
4.45
5.46
5.53
5.49
5.53
4.84
4.94
3.77
3.82
5.64
5.72
17.95
17.94
31.31
31.32
9.22
9.21
—
6.30
6.29
5.51
5.49
7.29
7.28
7.69
7.69
6.55
6.53
6.25
6.24
5.82
5.80
6.04
6.05
8.00
7.99
7.30
7.28
7.71
7.69
9.22
9.22
8.59
8.58
6.25
6.24
7.94
7.95
241-243
253-255
184-186
128-130
131-133
306-309
>320 dec)
228–230
218-220
222-224
213-215
246-249
154-156
276-278
165-167
64
70
75
69
71
69
67
65
73
70
65
40
31
87
66*3
3d
4b
4c
4d
8a
8b
8c
С24Н17BrN2O
С24Н17ClN2O5
С24Н16Cl2N2O5
С25Н19ClN2O5
С24Н18N2O
18.60
18.61
7.91
7.90
14.69
14.67
7.68
7.66
9a
9b
9c
—
С24Н17ClN2O
С25Н20N2O
9.22
9.21
—
10a
10b
12
13
С31H25N3O
—
С31H24СlN3O
С24Н17ClN2O5
С24Н20N2O
7.25
7.24
7.91
7.90
—
_______
* Recrystallization solvents: DMF for 2b-d, 4b-d, and 9a-c, 2-propanol for
10a, 10b, acetic acid for 3b-d, 8a-c, and 12, and 1:2 2-propanol–DMF for 13.
*2 Analysis data for Cl.
*3 Yield in method A.
The assignment of the signals for the methylene group protons was carried out through
NOE experiments (Table 2, Fig.1). The signal for the methine proton at C(5) is in the aromatic proton region,
which makes its observation difficult.
The behavior of salts 8 in the presence of nucleophiles proved unexpected. The characteristic
1,4-addition for 2-enimines [12] does not occur in this case. Thus, the reduction of salts 8a-c by excess NaBH4
leads to 10,11,15c,16-tetrahydro-10a,15b-diazadibenzo[a,e]pleiaden-11-ones 9a-c, as indicated by the
one-proton signal at 6.19-6.29 ppm observed along with two AB spin systems of the benzylamine methylene
group protons at C(10) and C(16) with ∆δ ~0.5 ppm. The signal for H-5 is found in the aromatic proton region due
to the anisotropic effect of the two adjacent benzene rings and its position in the spectrum of 9b (7.50 ppm) was
determined from the 1H NMR 2D spectra and the NOE experiments (Table 2, Fig. 1).
216

–
–
PhCH2N
ClO4
ClO4
+
N
PhCH2NH2
+
N
N
N
O
N
N
O
O
Me
Me
Me
6
7
PhCH2N
6
5
R1
R
–
R2
4
ClO4
+
N
1
N
[O]
PhCH2NH2
3a–c
N
O
N
O
R1
NaBH4
R2
10a,b
8a-c
N
N
O
9a-c
8–10 a R1 = R2 = H; b R1 = Cl, R2 = H; 8, 9 c R1 = H, R2 = Me
Ph
H
H
H
H
N
H
H
N
H
H
H
+
N
H
N
H
N
O
N
O
N
O
H
H
H
H
H
H
_
ClO4
H
H
H
9a
8a
10a
H
N
H
H
H
H
H
H
+
N
_
ClO4
H
N
O
N
O
H
H
H
H H
H
H
H
H
H
H
H
13
12
Fig. 1. Observed NOE for compounds 8a, 9a, 12, and 13.
217

218

219

1
The reaction of salts 8a,b with benzylamine leads to compounds with H NMR spectra displaying A2,
AB, and ABX spin systems for seven aliphatic protons in the aliphatic protons absorbtion region and a
downfield signal at 8.48 ppm. Taking account of the spectral behavior of imine 7 [11], these findings are in
accord with the structure of products such as 6-{2-[(benzylimino)methyl]phenyl}-7,12-dihydroisoquino-
[3,2-b][2]benzazepin-14(6H)-ones 10a and 10b. This hypothesis is also supported by the NOE experiments for
10a (see Experimental and Fig. 1) and the UV spectra. Thus, the great similarity of the electronic spectrum of
10a to the spectrum of 6,11-dihydro-13H-isoquino-[3,2-b]quinazolin-6-one [13] confirms the existence of a
2,3-cycloalkylated 4(3H)-quinazolone.
H
+
N
–
+
N
:
B
8
N
O
N
O
–
– HB
H
11
:
– B
HB
H
PhCH2
–
ClO4
N
+
N
N
– HB
PhCH2NH2
HClO4
10
N
O
N
O
HClO4
HB
12
The formation of imines 10a and 10b may be seen as initial deprotonation at C(16) by the action of the base
(benzylamine), which leads to an intermediate betaine 11. Further protonation gives the 11-oxo-5,10,10a,11-
tetrahydro-10a-aza-15b-azoniadibenzo[a,e]pleiadene cation (12), which is a structural analog of cation 6. Similar to
6, the addition of a primary amine at C(16) is accompanied by opening of the N(15a)–C(16) bond. Similar to imine 7,
imine 10a is converted by treatment with perchloric acid to 11-oxo-10,11-dihydro-10a-aza-15b-
azoniadibenzo[a,e]pleiadene perchlorate (12), whose formation was expected in the oxidation of salt 3a. This
1
reaction is reversible and imine 10a is reobtained upon the reaction of salt 12 with benzylamine. The H NMR
spectrum of 12 shows signals characteristic for the aromatic system of isoquino[2,3-a]quinazoline. The
assignment of these signals was supported by the NOE experiments (Table 2, Fig. 1). The total similarity of the
UV spectra of salts 6 and 12, indicating that these salts are isoelectronic, is final proof for the structure of salt 12.
We also found evidence for the proposed transformation scheme 8 → 11 → 12 → 10. In a comparative analysis
of the UV spectra of 8a, 12, and a mixture of 8a + Et3N in methanol (Fig. 2), we found that the absorption curve
for the mixture is extremely similar in form to the curves for 6 and 12.
Perchlorate 12 readily reacts with NaBH4 in methanol to give 4b,5,10,10a,11,15b,15c,16-octahydro-
10a,15b-diazadibenzo[a,e]pleiaden-11-one (13).
The same compound was obtained in the reduction of bromide 3a by a 10-fold excess of NaBH4 in
acetic acid–methanol. The use of acetic acid in the latter case proved necessary since the free base,
dibenzopleiadene 4a, which is readily formed in basic medium (in the absence of acetic acid), proved inert
toward the action of NaBH4 under these conditions.
220

N
NaBH4
NaBH4
AcOH
12
3a
N
O
13
The reaction is stereoselective as indicated by the single set of NMR signals of the raw reaction product.
Only the erythro isomer is formed in this reaction of the two theoretically possible diastereomeric products (with
cis and trans arrangement of the hydrogen atoms in the C(4b)–C(15c) fragment). This finding is supported by the
1H NMR spectral data for 13 in benzene-d6. The one-proton doublet at 4.54 ppm with J = 3.9 Hz,
ε, liters⋅mol-1⋅cm-1
200
300
400
λ, nm
Fig. 2. UV spectra of 6 (1), 8a (2), 12 (3), and a mixture of 8a and Et3N (4) in methanol.
characteristic for a vicinal cis proton coupling was assigned to H-15c. The final conclusion concerning the cis
structure of the reduction product was made using the results of a series of NOE experiments (Table 2, Fig. 1).
Using a modified Karplus equation, the H–C(15c)–C(4b)–H, H–C(15c)–C(5)–HB, and H–C(15c)–C(5)–HA dihedral
angles were found to be 48, 87, and 153°, respectively. Analysis of a molecular model showed that the values of
φ correspond to a distorted half-chair conformation of the tetrahydroisoquinoline ring atom (N(15b) is located in
the plane of the isoquinoquinazoline fragment, while atom C(15c) is located above this plane) and a distorted boat
conformation for the azepine ring (C(4b) and C(15c) are located above the plane, while atoms N(10a) is located below
the plane of the other atoms in the bicyclic system).
221

EXPERIMENTAL
1
The UV spectra for tablets in KBr were taken on an SP3-300 Pye Unicam spectrometer. The H NMR
spectra were taken on a Varian Mercury 400 spectrometer at 400 MHz, while the 13C NMR and COSY HH
spectra were taken on a Bruker-250 spectrometer at 63 and 250 MHz, respectively with TMS as the internal
standard. The UV spectra were taken on a Specord M400 spectrophotometer in methanol. The mass spectra were
recorded on a Nermag R10 mass spectrometer by the FAB method in DMSO (9a) and by the CI method (NH3)
in acetonitrile (9b). The melting points were taken on a Boetius block.
Spiro[R-5H-isoquino[2,3-a]quinazoline-7(12H)-2'-indan]-5-ones 2b-d were obtained by a procedure
described by Milanowski [3] of the corresponding isoquinoquinazoline 1b-d (0.5 mmol), 2-PrONa (0.1 g,
1.1 mmol), and o-xylylene dibromide (0.13 g, 0.5 mmol).
Ketone 2b. IR spectrum, ν, cm-1: 1635 br. (C=O). H NMR spectrum (CDCl3), δ, ppm (J, Hz): 8.33
1
o
m
m
o
(1H, J = 8.0, H-4); 7.69 (1H, d, J = 2.0, H-1); 7.46 (1H, dd, J = 2.0, J = 8.0, H-3); 7.38-7.20 (8H, m, HAr);
5.31 (2H, s, H-12); 4.28 (2H, d, 2J = 16.0, HA-1',3'); 3.33 (2H, d, 2J = 16.0, HB-1',3').
Ketone 2c. IR spectrum, ν, cm-1: 1635 br. (C=O). 1H NMR spectrum (CDCl3), δ, ppm (J, Hz): 8.19 (1H,
s, H-4); 7.61 (2H, m, H-1,2); 7.40-7.20 (8H, m, HAr, 5.34 (2H, s, H-12); 4.29 (2H, d, 2J = 16.0, HA-1',3'); 3.31
(2H, d, 2J = 16.0, HB-1',3').
Ketone 2d. IR spectrum, ν, cm-1: 1632 br. (C=O). 1H NMR spectrum (CDCl3), δ, ppm (J, Hz): 8.51 (1H,
d, mJ = 2.0, H-4); 7.88 (1H, dd, mJ = 2.0, oJ = 8.0, H-2); 7.57 (1H, d, oJ = 8.0, H-1); 7.40-7.20 (8H, m, HAr); 5.33
(2H, s, H-12); 4.28 (2H, d, 2J = 16.0, HA-1',3'); 3.32 (2H, d, 2J = HB-1',3').
11-Oxo-5,10,11,16-tetrahydro-4bH-10a-aza-15b-azoniadibenzo[a,e]pleiadenes Bromides 3b-d were
obtained according to the procedure described by Milanowski [3] of the corresponding
isoquinoquinazoline 1b-1d (0.5 mmol) and o-xylylene dibromide (0.13 g, 0.5 mmol). Heating times: 1 h for 1b,
3.5 h for 1c, and 1.5 h for 1d.
5,10,11,16-Tetrahydro-10a,15b-diazadibenzo[a,e]pleiaden-11-ones 4b-d were obtained by
a
procedure described by Milanowski [3] using Et3N.
11-Oxo-10,10a,11,16-tetrahydro-10a-aza-15b-azoniadibenzo[a,e]pleiadenes Perchlorates 8a-c. Salt
3a-c (5 mmol) was dissolved with heating in nitrobenzene (3 ml). The solution of, aqueous perchloric acid
(1 ml) was added and the mixture was heated at reflux for 10 min. After cooling, 2-propanol (20 ml) was added.
A yellow precipitate formed after 5 h. The precipitate was filtered off, washed with 2-propanol, and
recrystallized from acetic acid.
10,11,15c,16-Tetrahydro-10a,15b-diazadibenzo[a,e]pleiaden-11-ones 9a-c. NaBH4 (0.95 g, 25 mmol)
was added in small portions to a suspension of the corresponding dibenzopleiadene perchlorate 8a-c (5 mmol)
in methanol (10 ml). After the vigorous reaction, the mixture was heated at reflux for 15 min. The solvent was
evaporated off and the residue was treated with 15 ml 10% aq. NaOH. The solid colorless product was filtered
off, washed with water and, then, ethanol, and recrystallized from DMF.
Ketone 9a. Mass spectrum (FAB, MeCN), m/z (Irel., %): 351 [M+1]+ (60), 232 [M-118]+ (100), 202
[M-148]+ (15).
Ketone 9b. 13C NMR spectrum in CDCl3, δ, ppm: 160.57 (C-11); 147.73 (C-15a); 138.67 (C-11a);
138.07 (C-9a); 133.65 (C-4a); 133.56 (C-5a); 133.25 (C-16a); 115.53 (C-4b); 133.19-112.95 (C-1–C-9, C-12–
C-15); 74.85 (C-15c); 50.15 (C-10); 47.65 (C-16). Mass spectrum (CI, DMSO), m/z, (Irel., %): 385
[M+(NH3)2H]+ (100), 235 [M-149]+ (24).
6-{2-[(Benzylimino)methyl]phenyl}-7,12-dihydroquinazolino[3,2-b][2]benzazepin-14(6H)-ones
10a,b. Dibenzopleiadene perchlorate 8a or 8b (5 mmol) was dissolved with heating in benzylamine (3 ml).
Then, water (3 ml) was added to the cooled solution and the mixture was heated at reflux for 5 min. After
cooling, the oil was separated by decanting. The oil was triturated while added ethanol (4 ml) in small portions
until a colorless precipitate formed. The precipitate was filtered off and washed with ethanol.
222

Ketone 10a. IR spectrum, ν, cm-1: 1665 (C=O); 1640 (C=N). UV spectrum in methanol, λmax, nm
(ε·10-3): 253 (19.0); 280 (9.0, inflection), 310 (6.0), 322 (5.0). 1H NMR spectrum (CDCl3), δ, ppm (J, Hz): 8.48
o
3
3
(1H, s, CH=N); 8.13 (1H, d, J = 8.0, H-1); 7.85-6.80 (16H, m, ArH); 6.28 (1H, dd, J = 4.4, J = 11.2, H-6);
2
2
2
5.68 (1H, d, J = 15.0, HA-12); 5.07 (1H, d, J = 15.0, HB-12); 4.70 (1H, d, J = 13.5, CHAHBPh); 4.49 (1H, d,
2J = 13.5, CHACHBPh); 3.70-3.59 (2H, m, H-7). NOE (CDCl3), δ, ppm: {4.49} → 8.48 (η = 17%, CH=N);
{5.07} → 5.68 (η = 29%, HA-12); 6.28 (η = 28%, H-6); {6.28} → 5.07 (η = 27%, HB-12); 3.65 (η = 15%,
HA-7).
Ketone 10b. IR spectrum, ν, cm-1: 1660 (C=O), 1630 (C=N). H NMR spectrum (CDCl3), δ, ppm
1
o
3
(J, Hz): 8.61 (1H, s, CH=N); 8.01 (1H, d, J = 8.1, H-1); 7.78-6.93 (15H, m, HAr); 6.10 (1H, dd, J = 4.4,
3J = 11.2, H-6); 5.70 (1H, d, 2J = 15.0, HA-12); 5.24 (1H, d, 2J = 15.0, HB-12); 4.83 (1H, d, 2J = 13.5, CHAHBPh);
4.49 (1H, d, 2J = 13.5, CHAHBPh); 3.70-3.55 (2H, m, H-7).
11-Oxo-5,10,10a,11-tetrahydro-10a-aza-15b-azoniadibenzo[a,e]pleiadene
Perchlorate
(12).
Perchloric acid (1 ml) was added to a solution of quinazolino[2]benzazepine 10a (0.91 g, 2 mmol) in 2-propanol
(4 ml). The yellow precipitate, which formed after 1 h, was filtered off, washed with acetone, and recrystallized
from acetic acid. UV spectrum in methanol, λmax, nm (ε·10-3): 295 (15.5), 330 (13.0).
4b,5,10,10a,11,15b,15c,16-Octahydro-10a,15b-diazadibenzo[a,e]pleiaden-11-one (13). A. NaBH4
(0.11 g, 3 mmol) was added in small portions to a suspension of salt 12 (0.87 g, 2.5 mmol) in
methanol (5 ml). After the vigorous reaction, the mixture was heated at reflux for 30 min. The solvent was
evaporated off. The residue was treated with 10% aq. NaOH (5 ml). The solid, colorless crude product was
filtered off, washed with water and, then, ethanol, and recrystallized from DMF.
B. NaBH4 (0.95 g, 2.5 mmol) was added in small portions to a suspension of pleiadene salt 3a (1.55 g,
5 mmol) in a mixture of acetic acid (2 ml) and methanol (25 ml). After the vigorous reaction, the mixture was
heated at reflux for 15 min. After cooling, an additional NaBH4 (0.95 g, 2.5 mmol) was added and a solution of
acetic acid (1 ml) in methanol (5 ml) was added dropwise. The mixture was heated at reflux for 1 h. The solvent
was evaporated off at reduced pressure. The residue was treated with 10% aq. NaOH (20 ml). The solid crude
product was filtered off and washed with water and, then, ethanol.
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