New routes to fused isoquinolines

Article abstract of DOI:10.1002/1522-2675(200201)85:1<320::AID-HLCA320>3.0.CO;2-X

Treatment of 6,7-diethoxy-3,4-dihydroisoquinoline (8) and its 1-methyl derivative 12 with hydrazonoyl halides 10 in the presence of Et₃N in THF under reflux afforded the corresponding 5,6-dihydro-1,2,4-triazolo[3,4-a]isoquinolines 11 and 13, re

Full text of DOI:10.1002/1522-2675(200201)85:1<320::AID-HLCA320>3.0.CO;2-X

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Helvetica Chimica Acta Vol. 85 (2002)
New Routes to Fused Isoquinolines
by Enas M. Awad1)2), Nehal M. Elwan, and Hamdi M. Hassaneen*
Department of Chemistry, Faculty of Science, University of Cairo, Giza
and Anthony Linden and Heinz Heimgartner*
Organisch-chemisches Institut der Universit‰t Z¸rich, Winterthurerstrasse 190, CH-8057 Z¸rich
Treatment of 6,7-diethoxy-3,4-dihydroisoquinoline (8) and its 1-methyl derivative 12 with hydrazonoyl
halides 10 in the presence of Et3N in THF under reflux afforded the corresponding5,6-dihydro-1,2,4-
triazolo[3,4-a]isoquinolines 11 and 13, respectively, in high yield (Schemes 2 and 3). The products are formed
via regioselective 1,3-dipolar cycloaddition of the intermediate nitrilimines 9 with the isoquinoline CˆN bond.
Reaction of 6,7-diethoxy-3,4-dihydroisoquinoline-1-acetonitrile (4a) with ethyl a-cyanocinnamates 15 in the
presence of piperidine in refluxingMeCN yielded benzo[ a]quinolizin-4-ones 16 (Scheme 4). Under the same
conditions, 12 and arylidene malononitriles 19 reacted to give benzo[a]quinolizin-4-imines 20 (Scheme 5).
Instead of 15 and 19, mixtures of an aromatic aldehyde, and ethyl cyanoacetate or malononitrile, respectively,
can be used in a one-pot reaction.
Introduction. Within the class of fused isoquinolines with their cardiovascular [1],
anti-inflammatory [2], and antidepressant [3] activities, [1,2,4]triazolo[3,4-a]isoquino-
lines are of considerable pharmaceutical and agricultural interest [4 7]. Therefore, the
synthesis of this ringsystem is an attractive goal. A convenient approach is the 1,3-
dipolar cycloaddition of nitrilimines [8 10], generated by elimination of HX from
correspondinghydrazonoyl halides [11 13], to the C ˆN bond of 3,4-dihydroisoquin-
olines [12][14]. It has been shown that derivatives of type 1 can be obtained in high
yields with R1 ˆ H or alkyl [5][6][15][16]. On the other hand, 3,4-dihydroisoquinolin-
1-acetonitriles and hydrazonoyl halides in refluxingTHF in the presence of Et N
3
reacted to give pyrrolo[2,1-a]isoquinoline derivatives of type 2 via a cyclocondensation
reaction [15][17]. Spirocyclic adducts of type 3, which could have been formed by 1,3-
dipolar cycloaddition with the enamine tautomer of 3,4-dihydroisoquinolin-1-acet-
amide, have never been observed [6][15][17]3).
The recently reported results of the reaction of hydrazonoyl halides with 3,4-
dihydroisoquinolin-1-acetamide 4 in the presence of Et3N [17] are in pronounced
contrast to those published earlier [6]. Whereas the reaction of 5 in refluxingTHF
yielded only the cyclocondensation product 6, the structure of the product obtained
from the reaction in CH2Cl2 at room temperature was described as the cycloadduct 1a
1
)
Part of the Ph.D. thesis of E.M.A., University of Cairo, 2001. Present address: National Research Centre,
Tahrir Street, Dokki, Giza, Egypt.
Swiss Federal Scholar (−Bundesstipendiatin×) at the University of Z¸rich, October 1998 June 2000.
For a similar system in which cycloadditions with both the imine and the enamine tautomer occurred, see
[18].
2
3
)
)

Helvetica Chimica Acta Vol. 85 (2002)
321
R2
R2
N
N
NH
Ar
R1
Ar
N
N
NC
N
N
N
NC
N
R
Ar
1
2
3
(Scheme 1). In none of the reactions was the formation of a fused six-membered ring
observed (cf. [6][15]).
Scheme 1
Cl
RO
RO
RO
PhHN
N
CO2Et
N
N
CO2Et
5
RO
NC
N
N
4A
4B
CN
CH2Cl2, Et3N
r.t.
Ph
1a
[6]
Cl
PhHN
N
RO
RO
RO
RO
CO2Et
5
O
NH
CN
N
THF, Et3N
reflux
NC
N
NHPh
[17]
6
Isoquinoline derivatives with a fused six-membered ringat the C(1) ÀN(2) bond
have also been studied extensively (cf. [19 21]). Amongthem, benzo[ a]quinolizines
are well-known, and several methods for their preparation have been reported [22
27]. In the present paper, we introduce a new and general route to polyfunctional
benzo[a]quinolizine derivatives of type 7, which compares favorably to the reported
methods. The aim of this study is, on the one hand, to elaborate an efficient one-pot
synthesis startingfrom inexpensive reactants and leadingto 7 in good yields, and, on the
other hand, to prepare compounds that might have pharmacological activity.
EtO
X
N
EtO
R
CN
7
Ar
Results and Discussion. 1,3-Dipolar Cycloadditions with Nitrilimines. Treatment
of 6,7-diethoxy-3,4-dihydroisoquinoline (8) with nitrilimines 9a h, generated in situ
by the action of Et3N on the correspondinghydrazonoyl halides 10 in refluxingTHF for
6 h, afforded, in each case, a single product as evidenced by means of TLC and
1H-NMR analysis of the crude mixture. All products gave correct elemental analyses

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Helvetica Chimica Acta Vol. 85 (2002)
and mass spectra for cycloadducts of type 11 (Scheme 2 and Table 1), and IR and
1H-NMR spectra supported the proposed structures. For example, a singlet at ca.
1
6.6 ppm in the H-NMR spectrum (CDCl3) was characteristic for HÀC(10b).
Scheme 2
EtO
EtO
THF
R
NAr
R
C
N
+
N
N
EtO
reflux
EtO
N
N
11
8
9
Ar
Et3N - HX
X
10
NHAr
C
R
N
Table 1. Reaction of 3,4-Dihydroisoquinoline 8 with Nitrilimines 9a
h
9
R
Ar
11
Yield [%]
a
b
c
d
e
f
PhCO
PhCO
MeCO
MeCO
(Thiophen-2-yl)carbonyl
MeOCO
MeOCO
EtOCO
Ph
4-MeC6H4
Ph
4-MeC6H4
Ph
Ph
a
b
c
d
e
f
77
85
81
78
82
78
75
80
g
h
4-MeC6H4
4-MeClC6H4
g
h
The second dipolarophile that was selected for our studies was 6,7-diethoxy-3,4-
dihydro-1-methylisoquinoline (12), containingan −active Me group× at C(1). The ability
of 12 to behave either as a cyclic ketimine 12A or as an enamine 12B was discussed
earlier (e.g., [28][29]). Therefore, the main interest of the present study was whether
the addition of nitrilimines 9 occurs at the CˆN bond of 12A or the CˆC bond of 12B
(Scheme 3).
When the reactions of 12 with hydrazonoyl halides of type 10 were carried out
under the same conditions as those involving 8 (Et3N, THF, reflux), a single product
was formed in each case, which was a cycloadduct of the correspondingnitrilimine
(elemental analysis, MS). Structure 14 was eliminated on the basis of 1H-NMR
evidence: 14 was expected to reveal a singlet for CH2 and an NH signal, but both were
absent in the spectrum. Instead, the 1H-NMR spectra (CDCl3) of the products showed a
singlet for an Me group at ca. 1.9 ppm, which is compatible with structure 13. Indeed,
the Me absorption of ÀNˆC(Me)À in the startingmaterial 12 appeared at 2.3 ppm.
The shift of the signal by ca. 0.4 ppm towards higher field indicated the conversion of
j
j
this group into the saturated moiety ÀNÀC(Me)À due to the cycloaddition at the
CˆN bond. Furthermore, the molecular structure of 13e has been established by X-ray
crystallography (Fig.).

Helvetica Chimica Acta Vol. 85 (2002)
323
Scheme 3
EtO
EtO
N
EtO
CH3
R
N
EtO
12A
H3C
Ar
R
C
N NAr
9
N
N
13
14
EtO
EtO
EtO
EtO
NH
NH
CH2
Ar
N
N
R
12B
Figure. ORTEP Plot [30] of the molecular structure of 13e (arbitrary numberingof the atoms; 50% probability
ellisoids)

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Helvetica Chimica Acta Vol. 85 (2002)
Table 2. Reaction of 1-Methyl-3,4-dihydroisoquinoline 12 with Nitrilimines 9
9
R
Ar
13
Yield [%]
a
b
c
f
i
k
l
m
n
o
PhCO
PhCO
MeCO
MeOCO
EtOCO
PhNHCO
PhNHCO
Ph
Ph
4-MeC6H4
Ph
Ph
Ph
Ph
4-MeC6H4
Ph
Ph
a
b
c
d
e
f
g
h
i
81
83
80
81
85
86
85
80
78
80
PhCHˆCH
Thiophen-2-yl
4-NO2C6H4
k
In conclusion, under the reaction conditions chosen the 1,3-dipolar cycloaddition of
nitrilimines 9 with 3,4-dihydroisoquinoline 8 as well as with the 1-Me derivative 12
occurs exclusively at the CˆN bond (cf. also [5][6][15]). This is in contrast to the
recently reported reactions of hydrazonoyl halides with a 3,4-dihydroisoquinolin-1-
acetonitrile derivative [17] in which no 1,3-dipolar cycloaddition took place, but
pyrrolo[2,1-a]isoquinolines of type 2 were formed.
Synthesis of Benzo[a]quinolizine Derivatives. The reaction of 6,7-diethoxy-3,4-
dihydroisoquinoline-1-acetonitrile (4a) with a-cyanocinnamates 15 in refluxingMeCN
in the presence of piperidine afforded a single product 16 in each case, as evidenced by
TLC (Scheme 4). The structures of the benzo[a]quinolizine derivatives 16 were
1
established on the basis of their spectroscopic data (MS, H-NMR, IR) and their
elemental analyses. For example, the 1H-NMR spectra (CDCl3) revealed the absence of
the ester EtO group, while the IR spectra (KBr) exhibited three bands near 2221
(CꢀN), 2197 (CꢀN), and 1666 cmÀ1 (CO lactam). In the case of 16a, the 13C-NMR
spectrum of 16a ((D6)DMSO) supported the structure: characteristic signals appeared
at 160.3 ppm for a lactam CˆO, at 117.33 and 117.30 ppm for two CꢀN groups, and at
99.7 and 88.9 for two sp2-C-atoms bearingthe CN groups. The same products 16 were
also obtained in a one-pot reaction from equimolar amounts of 4a, ethyl cyanoacetate,
and arylaldehyde in refluxingMeCN in the presence of piperidine.
A conceivable reaction mechanism for the formation of 17 is proposed in Scheme 4:
Michael addition of the enamine structure 4aB (cf. [17]) with the cinnamates 15 yields
the adducts 17, which undergo a cyclization by elimination of EtOH, leading to 18. The
latter is then dehydrogenated by −aromatization× to yield 16.
In contrast to 4a, there is no spectroscopic evidence for the presence of an enamine
structure in the case of 3,4-dihydro-1-methylisoquinoline 12, although some reactions
have to be explained via the enamine tautomer (cf. [28][29]). Therefore, it was of
interest to compare the reactivity of 12 with that of 4a. Treatment of 12 with an
equimolar amount of arylidenemalononitrile 19 in MeCN and piperidine under reflux
yielded a single product in each case. For example, the reaction with benzylidene-
malononitrile (19, Arˆ Ph) gave a product with the molecular formula C24H23N3O2
(elemental analysis, MS). The same compound was formed in a one-pot reaction from
12, malononitrile, and benzaldehyde under the same conditions. The IR spectrum
(KBr) showed characteristic absorption bands at 3313 and 2202 cmÀ1 for NH and CꢀN,

Helvetica Chimica Acta Vol. 85 (2002)
325
Scheme 4
EtO
EtO
EtO
CO2Et
N
N
CO2Et
CN
EtO
CH
CN
ArCH
15
NC
CH
CN
4aA
Ar
or ArCHO + NCCH2CO2Et
MeCN , Piperidine
17
EtO
EtO
EtO
EtO
CO2Et
NH
CN
NH
CH
CN
NC
CH
Ar
4aB
- EtOH
EtO
EtO
EtO
EtO
O
O
N
N
CN
H
- ‘H2’
NC
NC
CN
H
Ar
16
18
Ar
a Ar = Ph; b Ar = 4-MeC6H4; c Ar = 4-MeOC6H4; d Ar =4-ClC6H4; e Ar = Thiophen-2-yl
respectively, in accordance with the structure of the imino benzo[a]quinolizine
derivative 20a (Scheme 5). The MS exhibited a molecular ion peak at m/z 385 with
1
high intensity, and the H-NMR spectrum (CDCl3) showed a characteristic singlet at
6.3 ppm assigned to HÀC(1) of 20a. Analogously, compounds 20b h were prepared
from 12 and the correspondingbenzylidenemalononitriles 19b h. The structures of
these products were established on the basis of their spectroscopic data. The 13C-NMR
spectrum ((D6)DMSO) of 20d showed signals at 148.0 and 120.4 ppm, which could be
assigned to the amidine C-atom (C(4)) and C(1), respectively. The characteristic
absorptions are at 118.2 (CꢀN) and 100.3 ppm (C(3)). Furthermore, propylidene-
malononitrile (19i) and 12 reacted to give the benzo[a]quinolizine 20i with an Et group
at C(2) instead of Ar.
The formation of 20 is proposed to proceed analogously to that of 16: Michael
addition of the enamine tautomer of 12 with 19 gives the adduct 21, which undergoes
cyclization to yield 22. Again, the latter is dehydrogenated spontaneously under the
reaction conditions to give the final product 20.
In summary, the reaction of 1-substituted 3,4-dihydroisoquinolines, which are able
to undergo an imine/enamine tautomerism, with a-cyanocinnamates and benzylidene-
malononitriles, respectively, opens a new and convenient route to benzo[a]quinazoline
derivatives.
We thank the analytical units of our institutes for spectra and analyses. E.M.A. thanks the Swiss Federal
Government for the provision of a National Scholarship for Foreign Students.

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Helvetica Chimica Acta Vol. 85 (2002)
Scheme 5
EtO
EtO
EtO
EtO
CN
MeCN , Piperidine
CN
CH
ArCH
+
N
N
or ArCHO + H2C(CN)2
CN
CH3
CH
CN
reflux
12
19
Ar
21
EtO
EtO
EtO
EtO
EtO
CN
CH
NH
N
NH
CN
NH
N
EtO
CN
H
- ‘H2’
CH
Ar
CN
H
Ar
Ar
20
22
a Ar = Ph; b Ar = 4-MeC6H4; c Ar = 4-MeOC6H4; d Ar = 4-ClC6H4; e Ar = 4-BrC6H4;
f Ar = Thiophen-2-yl; g Ar = 3,4-(MeO)2C6H3; h Ar = 3,4-(OCH2O)C6H3; i Ar = C2H5
Experimental Part
1. General. See [17]. Hydrazonoyl halides (chlorides or bromides) 10a,b [31], 10c,d [32], 10e [33], 10f,g
[34], 10h [35], 10i [36], 10k,l [37], 10m [38], 10n [39], and 10o [40], and 3,4-dihydroisoquinolines 8 [17] and 12
[41], a-cyanocinnamates 15a d [42] and 15e [43], and benzylidenemalononitriles 19a d [42], 19f [44], 19h
[45], and 19i [46] were prepared accordingto the procedures reported.
2. Synthesis of 1,5,6,10b-Tetrahydro-1,2,4-triazolo[3,4-a]isoquinoline Derivatives 11a h. To a soln. of a
hydrazonoyl halide 10 (5 mmol) and 6,7-diethoxy-3,4-dihydroisoquinoline (8; 1.1 g, 5 mmol) in THF (40 ml)
was added Et3N (1.4 ml, 10 mmol) at r.t., and the mixture was refluxed for 6 h. The solvent was evaporated i.v.,
and the residue was triturated with MeOH (10 ml) leadingto solidification. The crude product was crystallized
from EtOH or MeOH. The compounds 11a h with their physical data are listed below.
3-Benzoyl-8,9-diethoxy-1,5,6,10b-tetrahydro-1-phenyl-1,2,4-triazolo[3,4-a]isoquinoline (11a): 1.700 g
.
‡
‡
(77%). M.p. 1148 (EtOH). IR: 1643 (CO). EI-MS: 442 (13, [M ‡ 1] ), 441 (49, M ), 440 (100), 105 (15),
77 (6). Anal. calc. for C27H27N3O3 (441.54): C 73.45, H 6.16, N 9.52; found: C 73.30, H 6.02, N 9.24.
3-Benzoyl-8,9-diethoxy-1,5,6,10b-tetrahydro-1-(4-methylphenyl)-1,2,4-triazolo[3,4-a]isoquinoline (11b):
1.936 g(85%). M.p. 116 8 (EtOH). IR: 1635 (CO). 1H-NMR: 1.29, 1.45 (2t, J ˆ 7, 2 MeCH2); 2.30 (s, Me);
2.85 (m, CH2); 3.88 (m, CH2N); 4.10 (m, 2 CH2O); 6.54 (s, HÀC(10b)); 6.68, 6.75 (2s, 2 arom. H); 7.10 7.60 (m,
.
‡
‡
9 arom. H). EI-MS: 456 (14, [M ‡ 1] ), 455 (69, M ), 454 (100), 440 (8), 349 (6), 105 (15). Anal. calc. for
C28H29N3O3 (455.57): C 73.83, H 6.41, N 9.22; found; C 73.54, H 6.14, N 9.02.
3-Acetyl-8,9-diethoxy-1,5,6,10b-tetrahydro-1-phenyl-1,2,3-triazolo[3,4-a]isoquinoline (11c): 1.537 g(81%).
M.p. 1078 (EtOH). IR: 1672 (CO). 1H-NMR: 1.28, 1.45 (2t, J ˆ 7, 2 MeCH2); 2.45 (s, Me); 2.71, 2.85 (2m, CH2);
3.79 (q, J ˆ 7, CH2O); 3.95 (m, CH2N); 4.08 (q, J ˆ 7, CH2O); 6.54 (s, HÀC(10b)); 6.68, 6.72 (2s, 2 arom. H); 6.96
.
‡
‡
(m, 1 arom. H); 7.21 (m, 2 arom. H); 7.31 (m, 2 arom. H). EI-MS: 380 (11, [M ‡ 1] ), 379 (60, M ), 378 (100),
350 (5), 334 (5). Anal. calc. for C22H25N3O3 (379.46): C 69.64, H 6.63, N 11.07; found: C 69.92, H 6.44, N 11.19.
3-Acetyl-8,9-diethoxy-1,5,6,10b-tetrahydro-1-(4-methylphenyl)-1,2,4-triazolo[3,4-a]isoquinoline (11d):
1.535 g(78%). M.p. 111 8 (EtOH). IR: 1680 (CO). 1H-NMR: 1.32, 1.51 (2t, J ˆ 7, 2 MeCH2); 2.33, 2.44 (2s,
2 Me); 2.91 (m, CH2); 3.80 (m, CH2N); 4.12 (m, 2 CH2O); 6.40 (s, HÀC(10b)); 6.74, 6.84 (2s, 2 arom. H); 7.12
7.62 (m, 4 arom. H). Anal. calc. for C23H27N3O3 (393.49): C 70.21, H 6.91, N 10.68; found: C 70.50, H 6.58,
N 10.41.
8,9-Diethoxy-1,5,6,10b-tetrahydro-1-phenyl-3-[(thiophen-2-yl)carbonyl]-1,2,4-triazolo[3,4-a]isoquinoline
.
‡
‡
(11e): 1.835 g(82%). M.p. 248 8 (EtOH). IR: 1681 (CO). EI-MS: 448 (15, [M ‡ 1] ), 447 (61, M ), 446 (100),
111 (14). Anal. calc. for C25H25N3O3S (447.57): C 67.09, H 5.63, N 9.39, S 7.16; found: C 67.36, H 5.88, N 9.47,
S 7.02.

Helvetica Chimica Acta Vol. 85 (2002)
327
Methyl 8,9-Diethoxy-1,5,6,10b-tetrahydro-1-phenyl-1,2,4-triazolo[3,4-a]isoquinoline-3-carboxylate (11f):
1.542 g(78%). M.p. 116 8 (EtOH). IR: 1722 (CO). 1H-NMR: 1.20, 1.36 (2t, J ˆ 7, 2 MeCH2); 2.75 (m, CH2);
3.62 (m, CH2N); 3.73 (q, J ˆ 7, CH2O); 3.80 (s, MeO); 3.99 (q, J ˆ 7, CH2O); 6.37 (s, HÀC(10b)); 6.61, 6.62 (2s, 2
arom. H); 6.82 7.27 (m, 5 arom. H). Anal. calc. for C22H25N3O4 (395.46): C 66.82, H 6.37, N 10.63; found;
C 66.54, H 6.08, N 10.42.
Methyl 8,9-Diethoxy-1,5,6,10b-tetrahydro-1-(4-methylphenyl)-1,2,4-triazolo[3,4-a]isoquinoline-3-carbox-
.
‡
‡
ylate (11g): 1.536 g(75%). M.p. 132 8 (EtOH). IR: 1716 (CO). EI-MS: 410 (8, [M ‡ 1] ), 409 (39, M ), 408
(100), 350 (7), 349 (19), 295 (6), 105 (6), 91 (5). Anal. calc. for C23H27N3O4 (409.49): C 67.47, H 6.64, N 10.26;
found: C 67.21, H 6.45, N 10.12.
Ethyl 1-(4-Chlorophenyl)-8,9-diethoxy-1,5,6,10b-tetrahydro-1,2,4-triazolo[3,4-a]isoquinoline-3-carboxylate
(11h): 1.776 g(80%). M.p. 141 8 (EtOH). IR: 1719 (CO). 1H-NMR: 1.24, 1.27, 1.41 (3t, J ˆ 7, 3 MeCH2); 2.82 (m,
CH2); 3.72 (m, CH2N); 3.85, 4.08, 4.35 (3q, J ˆ 7, 3 CH2O); 6.36 (s, HÀC(10b)); 6.61, 6.70 (2s, 2 arom. H); 7.10
(m, 2 arom. H); 7.25 (m, 2 arom. H). Anal. calc. for C23H26N3O4Cl (443.93): C 62.23, H 5.90, N 9.47; found: C
62.51, H 5.75, N 9.18.
3. Synthesis of 1,5,6,10b-Tetrahydro-10b-methyl-1,2,4-triazolo[3,4-a]isoquinoline Derivatives 13a k. These
compounds were prepared accordingto the protocol in Sect. 2 with 6,7-diethoxy-3,4-dihydro-1-methylisoquino-
line 12 instead of 8. The prepared compounds with their physical data are listed below.
3-Benzoyl-8,9-diethoxy-1,5,6,10b-tetrahydro-10b-methyl-1-phenyl-1,2,4-triazolo[3,4-a]isoquinoline (13a):
.
‡
‡
1.845 g(81%). M.p. 118 8 (MeOH). IR: 1665 (CO). EI-MS: 456 (6, [M ‡ 1] ), 455 (8, M ), 442 (6), 441
(45), 440 (100), 412 (5), 396 (13), 383 (7), 350 (5), 327 (7), 105 (37), 77 (17). Anal. calc. for C28H29N3O3
(455.56): C 73.83, H 6.41, N 9.22; found: C 73.71, H 6.54, N 9.27.
3-Benzoyl-8,9-diethoxy-1,5,6,10b-tetrahydro-10b-methyl-1-(4-methylphenyl)-1,2,4-triazolo[3,4-a]isoquino-
line (13b): 1.949 g(83%). M.p. 119 8 (EtOH). IR: 1665 (CO). 1H-NMR: 1.19, 1.40 (2t, J ˆ 7, 2 MeCH2); 2.10, 2.30
(2s, 2 Me); 2.42, 2.92 (2m, CH2); 3.32 (q, J ˆ 7, CH2O); 3.50 (m, 1 H of CH2N); 4.02 (q, J ˆ 7, CH2O); 4.62 (m, 1
.
‡
‡
H of CH2N); 5.95, 6.45 (2s, 2 arom. H); 7.05 8.10 (m, 9 arom. H). EI-MS: 470 (1, [M ‡ 1] ), 469 (1, M ), 456
(30), 455 (100), 454 (86), 105 (37), 77 (26). Anal. calc. for C29H31N3O3 (469.59): C 74.18, H 6.65, N 8.95; found:
C 74.51, H 6.93, N 8.84.
3-Acetyl-8,9-diethoxy-1,5,6,10b-tetrahydro-10b-methyl-1-phenyl-1,2,4-triazolo[3,4-a]isoquinoline (13c):
1.574 g(80%). M.p. 104 8 (MeOH). IR: 1676 (CO). 1H-NMR: 1.18, 1.40 (2t, J ˆ 7, 2 MeCH2); 2.09 (s, Me);
2.35, 2.88 (2m, CH2); 2.44 (s, Me); 3.26 (q, J ˆ 7, CH2O); 3.48 (m, 1 H of CH2N); 3.99 (q, J ˆ 7, CH2O); 4.65 (m, 1
H of CH2N); 5.97, 6.44 (2s, 2 arom. H); 7.10 7.36 (m, 5 arom. H). Anal. calc. for C23H27N3O3 (393.49): C 70.21, H
6.91, N 10.68; found: C 70.46, H 6.72, N 10.44.
Methyl 8,9-Diethoxy-1,5,6,10b-tetrahydro-10b-methyl-1-phenyl-1,2,4-triazolo[3,4-a]isoquinoline-3-carbox-
ylate (13d): 1.658 g(81%). M.p. 114 8 (MeOH). IR: 1713 (CO). 1H-NMR: 1.18, 1.40 (2t, J ˆ 7, 2 MeCH2);
2.08 (s, Me); 2.44, 2.94 (2m, CH2); 3.27 (q, J ˆ 7, CH2O); 3.45 (m, 1 H of CH2N); 3.85 (s, MeO); 3.99 (q, J ˆ 7,
‡
CH2O); 4.51 (m, 1 H of CH2N); 5.94, 6.45 (2s, 2 arom. H); 7.07 7.30 (m, 5 arom. H). EI-MS: 410 (2, [M ‡ 1] ),
.
‡
409 (1, M ), 396 (28), 395 (100), 350 (15), 234 (19), 91 (10), 77 (14). Anal. calc. for C23H27N3O4 (409.49): C
67.47, H 6.64, N 10.26; found: C 67.25, H 6.42, N 10.01.
Ethyl 8,9-Diethoxy-1,5,6,10b-tetrahydro-10b-methyl-1-phenyl-1,2,4-triazolo[3,4-a]isoquinoline-3-carboxy-
1
late (13e): 1.800 g(85%). M.p. 137 8 (MeOH). IR: 1708 (CO). H-NMR: 1.19, 1.35, 1.45 (3t, J ˆ 7, 3 MeCH2);
2.07 (s, Me); 2.44, 2.99 (2m, CH2); 3.29 (q, J ˆ 7, CH2O); 3.50 (m, 1 H of CH2N); 4.01, 4.35 (2q, J ˆ 7, 2 CH2O);
4.54 (m, 1 H of CH2N); 5.93, 6.45 (2s, 2 arom. H); 7.09 7.33 (m, 5 arom. H). Anal. calc. for C24H29N3O4 (423.51):
C 68.07, H 6.89, N 9.92; found: C 68.24, H 6.72, N 9.65.
Recrystallization from MeOH gave suitable crystals for an X-ray-diffraction analysis.
8,9-Diethoxy-1,5,6,10b-tetrahydro-10b-methyl-1,N-diphenyl-1,2,4-triazolo[3,4-a]isoquinoline-3-carbox-
1
amide (13f): 2.023 g(86%). M.p. 113 8 (EtOH). IR: 3210 (NH), 1670 (CO). H-NMR: 1.40, 1.52 (2t, J ˆ 7, 2
MeCH2); 1.83 (s, Me); 2.42, 2.73 (2m, CH2); 3.02, 3.82 (2m, CH2N); 3.91, 4.14 (2q, J ˆ 7, 2 CH2O); 6.63, 6.84 (2s, 2
.
‡
‡
arom. H); 7.10 7.82 (m, 10 arom. H); 9.13 (s, NH). EI-MS: 471 (6, [M ‡ 1] ), 470 (3, M ), 458 (6), 457 (35),
456 (100), 455 (99), 428 (6), 351 (5), 91 (11), 77 (15). Anal. calc. for C28H30N4O3 (470.58): C 71.47, H 6.42, N
11.91; found: C 71.33, H 6.25, N 11.84.
8,9-Diethoxy-1,5,6,10b-tetrahydro-10b-methyl-1-(4-methylphenyl)-N-phenyl-1,2,4-triazolo[3,4-a]isoquino-
1
line-3-carboxamide (13g): 2.060 g(85%). M.p. 165 8 (EtOH). IR: 3255 (NH), 1681 (CO). H-NMR: 1.42, 1.54
(2t, J ˆ 7, 2 MeCH2); 1.72, 2.33 (2s, 2 Me); 2.42, 2.64 (2m, CH2); 3.14, 3.73 (2m, CH2N); 3.82, 4.14 (2q, J ˆ 7, 2
CH2O); 6.53, 6.71 (2s, 2 arom. H); 7.00 7.72 (m, 9 arom. H); 9.11 (s, NH). Anal. calc. for C29H32N4O3 (484.61): C
71.88, H 6.65, N 11.56; found: C 71.62, H 6.82, N 11.34.

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Helvetica Chimica Acta Vol. 85 (2002)
8,9-Diethoxy-1,5,6,10b-tetrahydro-10b-methyl-1,3-diphenyl-1,2,4-triazolo[3,4-a]isoquinoline (13h): 1.710 g
(80%). M.p. 1298 (MeOH). 1H-NMR: 1.33, 1.43 (2t, J ˆ 7, 2 MeCH2); 1.80 (s, Me); 2.38, 2.80 (2m, CH2); 3.13,
3.70 (2m, CH2N); 3.82, 4.04 (2q, J ˆ 7, 2 CH2O); 6.55, 6.56 (2s, 2 arom. H); 6.96 7.78 (m, 10 arom. H). EI-MS:
.
‡
‡
429 (6), 428 (32, [M ‡ 1] ), 427 (77, M ), 414 (53), 413 (77), 412 (100), 368 (71), 355 (38), 326 (25), 310 (24),
204 (17), 194 (31), 185 (11), 176 (29), 104 (9), 92 (16), 77 (31). Anal. calc. for C27H29N3O2 (427.55): C 75.86, H
6.83, N 9.83; found: C 75.72, H 6.63, N 9.87.
8,9-Diethoxy-1,5,6,10b-tetrahydro-10b-methyl-1-phenyl-3-(2-phenylethenyl)-1,2,4-triazolo[3,4-a]isoquino-
line (13i): 1.769 g(78%). M.p. 103 8 (MeOH). 1H-NMR: 1.28, 1.40 (2t, J ˆ 7, 2 MeCH2); 1.88 (s, Me); 2.48, 2.98
(2m, CH2); 3.26 (m, 1 H of CH2N); 3.65 (q, J ˆ 7, CH2O); 3.86 (m, 1 H of CH2N); 4.06 (q, J ˆ 7, CH2O); 6.38,
6.55 (2s, 2 arom. H); 6.77 (d, J ˆ 16, 1 H of PhCHˆCH); 7.03 (m, 1 arom. H); 7.10 7.39 (m, 8 H); 7.51 (m, 2
.
‡
‡
arom. H). EI-MS: 454 (6, [M ‡ 1] ), 453 (15, M ), 440 (8), 439 (48), 438 (100), 394 (18), 381 (8), 212 (6), 91
(16). Anal. calc. for C29H31N3O2 (453.59): C 76.80, H 6.88, N 9.26; found: C 76.54, H 6.62, N 9.47.
8,9-Diethoxy-1,5,6,10b-tetrahydro-10b-methyl-1-(4-nitrophenyl)-3-(thiophen-2-yl)-1,2,4-triazolo[3,4-a]iso-
quinoline (13k): 1.914 g(80%). M.p. 162 8 (MeOH). 1H-NMR: 1.25, 1.43 (2t, J ˆ 7, 2 MeCH2); 1.80 (s, Me); 2.33,
2.70 (2m, CH2); 3.12, 3.80 (2m, CH2N); 3.71, 4.01 (2q, J ˆ 7, 2 CH2O); 6.55, 6.70 (2s, 2 arom. H); 6.82 8.20 (m, 7
arom. H). Anal. calc. for C25H26N4O4S (478.58): C 62.75, H 5.47, N 11.71, S 6.70; found: C 62.48, H 5.65, N 11.62,
S 6.60.
4. Synthesis of Benzo[a]quinolizinone Derivatives 16a e. Method A: A mixture of equimolar amounts of
the appropriate aryl aldehyde, ethyl cyanoacetate, and 6,7-diethoxy-3,4-dihydroisoquinolin-1-acetonitrile (4a)
in MeCN (40 ml) and piperidine (4 drops) was heated under reflux for 6 h. The solvent was evaporated i.v., and
the residue was triturated with MeOH (10 ml), resultingin solidification. The crude product was crystallized
from EtOH to give 16a e.
MethodB: To a soln. of 4a (1.29 g, 5 mmol) and ethyl a-cyanocinnamates 15a e (5 mmol) in MeCN
(40 ml) was added piperidine (4 drops) at r.t. Similar treatment of the mixture as in Method A gave products that
were identical in all respects (m.p., mixed m.p., IR, 1H-NMR, MS) with those obtained by Method A. The
products 16a e obtained and their physical data are listed below.
9,10-Diethoxy-6,7-dihydro-4-oxo-2-phenylbenzo[a]quinolizine-1,3-dicarbonitrile (16a): 1.543 g(75%).
M.p. 2248 (EtOH). IR: 2214, 2195 (CN), 1666 (CO). 1H-NMR: 1.28, 1.45 (2t, J ˆ 7, 2 MeCH2); 2.88 3.05
(m, CH2); 3.8 (m, CH2N); 4.10 (q, J ˆ 7, 2 CH2O); 6.45 7.35 (m, 7 arom. H). 13C-NMR ((D6)DMSO): 14.4, 14.5
(2 MeCH2); 26.1 (CH2); 40.4 (CH2N); 64.20, 64.24 (2 CH2O); 88.9, 99.7 (C(1), C(3)); 111.7, 113.6, 115.0 (3 C);
117.30, 117.33 (2 CN); 128.2, 128.6, 130.5, 134.0, 134.1, 146.1, 152.9, 153.5, 158.2 (14 C); 160.3 (C(4)ˆO). EI-MS:
.
‡
411 (100, M ), 382 (42), 354 (89), 339 (17), 326 (26), 313 (34), 280 (20), 242 (8), 214 (11), 171 (13), 129 (11),
107 (13), 77 (5). Anal. calc. for C25H21N3O3 (411.46): C 72.98, H 5.14, N 10.21; found: C 72.75, H 5.02, N 10.06.
9,10-Diethoxy-6,7-dihydro-(4-methylphenyl)-4-oxobenzo[a]quinolizine-1,3-dicarbonitrile (16b): 1.638 g
(77%): M.p. 2208 (EtOH). IR: 2214, 2189 (CN), 1666 (CO). 1H-NMR: 1.41 1.59 (m, 2 MeCH2); 2.45 (s,
Me); 2.95 (t-like, CH2); 4.15 4.39 (m, CH2N, 2 CH2O); 6.80 (s, 1 arom. H); 7.32 7.50 (m, 4 arom. H); 7.93 (s, 1
.
‡
arom. H). EI-MS: 425 (20, M ), 368 (99), 313 (51), 218 (55), 160 (43), 137 (34), 129 (100), 123 (53), 109 (44),
103 (51), 97 (37), 83 (73). Anal. calc. for C26H23N3O3 (425.49): C 73.40, H 5.44, N 9.88; found: C 73.13, H 5.25, N
9.72.
9,10-Diethoxy-6,7-dihydro-2-(4-methoxyphenyl)-4-oxobenzo[a]quinolizine-1,3-dicarbonitrile (16c): 1.766 g
(80%). M.p. 2048 (EtOH). IR: 2214, 2197 (CN), 1658 (CO). 1H-NMR: 1.40 1.59 (m, 2 MeCH2); 2.95 (t-like,
CH2); 3.88 (s, MeO); 4.10 4.35 (m, CH2N, 2 CH2O); 6.80 (s, 1 arom. H); 7.05 (d-like, 2 arom. H); 7.55 (d-like, 2
.
‡
arom. H); 7.93 (s, 1 arom. H). EI-MS: 441 (15, M ), 383 (54), 368 (100), 341 (51), 284 (28), 262 (39), 242 (45),
239 (55), 193 (10), 187 (40), 146 (50), 125 (34), 112 (100), 102 (68). Anal. calc. for C26H23N3O4 (441.49): C 70.74,
H 5.25, N 9.52; found: C 70.52, H 5.14, N 9.36.
2-(4-Chlorophenyl)-9,10-diethoxy-6,7-dihydro-4-oxobenzo[a]quinolizine-1,3-dicarbonitrile (16d): 1.739 g
(78%). M.p. 2208 (EtOH). IR: 2221, 2197 (CN), 1666 (CO). 1H-NMR: 1.40 1.59 (m, 2 MeCH2); 2.95 (t-
like, CH2); 4.09 4.36 (m, CH2N, 2 CH2O); 6.82 (s, 1 arom. H); 7.45 7.60 (m, 4 arom. H); 7.90 (s, 1 arom. H). EI-
.
‡
MS: 446 (31, M ), 445 (100), 388 (49), 354, 296 (18), 268 (8), 250 (44), 242 (16), 214 (11), 191 (24), 169 (32),
128 (25), 108 (59), 77 (15). Anal. calc. for C25H20N3O3Cl (445.91): C 67.34, H 4.52, N 9.42; found: C 67.16, H 4.41,
N 9.22.
9,10-Diethoxy-6,7-dihydro-4-oxo-2-(thiophen-2-yl)benzo[a]quinolizine-1,3-dicarbonitrile (16e): 1.670 g
(80%). M.p. 2658 (EtOH). IR: 2210, 2197 (CN), 1662 (CO). 1H-NMR: 1.41 1.59 (m, 2 MeCH2); 2.95 (t-
like, CH2); 4.13 4.35 (m, CH2N, 2 CH2O); 6.80 (s, 1 arom. H); 7.21 7.73 (m, 3 arom. H); 7.92 (s, 1 arom. H).
Anal. calc. for C23H19N3O3S (417.49): C 66.17, H 4.58, N 10.07; found: C 66.11, H 4.53, N 10.01.

Helvetica Chimica Acta Vol. 85 (2002)
329
5. Synthesis of Benzo[a]quinolizine Derivatives 20a i. Method A: Equimolar amounts of 12, the
appropriate aldehyde, and malononitrile in MeCN, in the presence of piperidine, were heated under reflux
for 3 h. The solvent was evaporated i.v., and the residue was triturated with MeOH (10 ml), leadingto
solidification. The crude product was crystallized from EtOH or MeOH.
Method B: To a soln. of 12 (1.2 g, 5 mmol) and arylidinemalononitrile 19 (5 mmol) in MeCN (40 ml) was
added piperidine (0.5 ml) at r.t., and the mixture was refluxed for 3 h. Workup as in Method A yielded products
identical in all respects to those obtained from Method A. The compounds 20a i prepared together with their
physical data are listed below.
9,10-Diethoxy-6,7-dihydro-4-imino-2-phenyl-4H-benzo[a]quinolizine-3-carbonitrile (20a): 1.735 g(90%).
M.p. 1768 (EtOH). IR: 3313 (NH), 2202 (CN). 1H-NMR: 1.40 1.58 (m, 2 MeCH2); 2.90 3.03 (m, CH2); 4.03
4.25 (m, CH2N, CH2O); 4.27 4.39 (m, CH2O); 6.30, 6.76, 6.88, 7.20 (4s, 3 arom. H, NH); 7.50 7.71 (m, 5 arom.
.
‡
H). EI-MS: 385 (100, M ), 356 (70), 328 (27), 300 (16), 165 (9). Anal. calc. for C24H23N3O2 (385.50): C 74.78, H
6.01, N 10.90; found: C 74.54, H 5.82, N 10.73.
9,10-Diethoxy-6,7-dihydro-4-imino-2-(4-methylphenyl)-4H-benzo[a]quinolizine-3-carbonitrile (20b):
1.740 g(87%). M.p. 184 8 (EtOH). IR: 3312 (NH), 2197 (CN). 1H-NMR: 1.40 1.56 (m, 2 MeCH2); 2.40 (s,
Me); 2.90 3.02 (m, CH2); 4.03 4.23 (m, CH2N, CH2O); 4.27 4.38 (m, CH2O); 6.23, 6.75, 6.88, 7.30 (4s, 3 arom.
H, NH); 7.40 (d-like, 2 arom. H); 7.53 (d-like, 2 arom. H). Anal. calc. for C25H25N3O2 (399.53): C 75.17, H 6.30, N
10.52; found: C 75.36, H 6.54, N 10.41.
9,10-Diethoxy-6,7-dihydro-4-imino-2-(4-methoxyphenyl)-4H-benzo[a]quinolizine-3-carbonitrile (20c):
1.808 g(87%). M.p. 148 8 (EtOH). IR: 3320 (NH), 2200 (CN). 1H-NMR: 1.41 1.56 (m, 2 MeCH2); 2.90
3.02 (m, CH2); 3.90 (s, MeO); 4.04 4.23 (m, CH2N, CH2O); 4.26 4.37 (m, CH2O); 6.23, 6.75, 6.87 (3s, 2 arom.
.
‡
H, NH); 7.01 (d-like, 2 arom. H); 7.20 (s, 1 arom. H); 7.61 (d-like, 2 arom. H). EI-MS: 415 (100, M ), 414 (95),
386 (89), 358 (21), 330 (16), 300 (5), 180 (14). Anal. calc. for C25H25N3O3 (415.53): C 72.27, H 6.06, N 10.11;
found: C 72.54, H 6.17, N 10.02.
2-(4-Chlorophenyl)-9,10-diethoxy-6,7-dihydro-4-imino-4H-benzo[a]quinolizine-3-carbonitrile (20d):
1.785 g(85%). M.p. 217 8 (EtOH). IR: 3312 (NH), 2203 (CN). 1H-NMR: 1.41 1.57 (m, 2 MeCH2); 2.91
3.02 (m, CH2); 4.04 4.24 (m, CH2N, CH2O); 4.28 4.38 (m, CH2O); 6.20, 6.75, 6.88, 7.30 (4s, 3 arom. H, NH);
7.44 7.62 (m, 4 arom. H). 13C-NMR ((D6)DMSO): 15.3 (2 MeCH2); 27.1 (CH2); 46.0 (CH2N); 64.7, 65.1 (2
CH2O); 100.3 (C(3)); 112.2, 112.4 (2 C); 118.2 (CN); 120.4, 129.4, 130.6, 130.9, 135.5, 136.3, 148.1, 152.3, 154.4
(14 C); 157.2 (CˆNH). Anal. calc. for C24H22N3O2Cl (419.91): C 68.65, H 5.28, N 10.01; found: C 68.91, H 5.54, N
9.92.
2-(4-Bromophenyl)-9,10-diethoxy-6,7-dihydro-4-imino-4H-benzo[a]quinolizine-3-carbonitrile (20e):
1.857 g(80%). M.p. 225 8 (EtOH). IR: 3312 (NH), 2202 (CN). 1H-NMR: 1.40 1.56 (m, 2 MeCH2); 2.90
3.03 (m, CH2); 4.04 4.24 (m, CH2N, CH2O); 4.28 4.39 (m, CH2O); 6.20, 6.75, 6.80, 7.30 (4s, 3 arom. H, NH);
.
‡
7.50 (d-like, 2 arom. H); 7.71 (d-like, 2 arom. H). EI-MS: 464 (25, M ), 408 (6), 359 (32), 267 (8), 123 (18), 83
(20), 77 (14), 69 (19), 56 (100). Anal. calc. for C24H22N3O2Br (464.37): C 62.08, H 4.77, N 9.05; found: C 62.25, H
4.72, N 9.00.
9,10-Diethoxy-6,7-dihydro-4-imino-2-(thiophen-2-yl)-4H-benzo[a]quinolizine-3-carbonitrile (20f): 1.605 g
(82%). M.p. 1908 (EtOH). IR: 3316 (NH), 2197 (CN). 1H-NMR: 1.45 1.57 (m, 2 MeCH2); 2.91 3.03 (m,
CH2); 4.08 4.23 (m, CH2N, CH2O); 4.27 4.36 (m, CH2O); 6.35, 6.75, 6.86, 7.26 (4s, 3 arom. H, NH); 7.44, 7.61,
7.94 (3 br. s, 3 arom. H). Anal. calc. for C22H21N3O2S (391.49): C 67.50, H 5.40, N 10.73, S 8.19; found: C 67.82, H
5.08, N 10.52, S 8.04.
9,10-Diethoxy-6,7-dihydro-4-imino-2-(3,4-dimethoxyphenyl)-4H-benzo[a]quinolizine-3-carbonitrile (20g):
1.916 g(86%). M.p. 185 8 (MeOH). IR: 3321 (NH), 2194 (CN). 1H-NMR: 1.39 1.57 (m, 2 MeCH2); 2.90 3.01
(m, CH2); 3.94, 4.00 (2s, 2 MeO); 4.05 4.23 (m, CH2N, CH2O); 4.26 4.38 (m, CH2O); 6.30, 6.75, 6.86, 7.10 (4s, 3
arom. H, NH); 7.24 7.34 (m, 3 arom. H). Anal. calc. for C26H27N3O4 (445.53): C 70.10, H 6.10, N 9.43; found: C
70.32, H 6.34, N 9.15.
9,10-Diethoxy-6,7-dihydro-4-imino-2-[3,4-(methylenedioxy)phenyl]-4H-benzo[a]quinolizine-3-carbonitrile
(20h): 1.890 g(88%). M.p. 172 8 (MeOH). IR: 3311 (NH), 2201 (CN). 1H-NMR: 1.42 1.57 (m, 2 MeCH2);
2.90 3.02 (m, CH2); 4.04 4.22 (m, CH2N, CH2O); 4.28 4.38 (m, CH2O); 6.10 (s, CH2O2); 6.21, 6.75, 6.83, 7.04
.
‡
(4s, 3 arom. H, NH); 7.10 7.31 (m, 3 arom. H). EI-MS: 429 (14, M ), 428 (14), 359 (38), 299 (19), 267 (11), 201
(14), 171 (16), 123 (16), 102 (43), 56 (100). Anal. calc. for C25H23N3O4 (429.49): C 69.92, H 5.39, N 9.78; found: C
69.64, H 5.56, N 9.62.
9,10-Diethoxy-2-ethyl-6,7-dihydro-4-imino-4H-benzo[a]quinolizine-3-carbonitrile (20i): 1.383 g(82%).
M.p. 1738 (EtOH). IR: 3319 (NH), 2198 (CN). 1H-NMR: 1.30 (t, J ˆ 7, MeCH2); 1.42 1.57 (m, 2 MeCH2);
2.64 (q, J ˆ 7, MeCH2); 2.85 2.96 (m, CH2); 4.08 4.19 (m, CH2N, CH2O); 4.20 4.32 (m, CH2O); 6.10, 6.74,

330
Helvetica Chimica Acta Vol. 85 (2002)
.
‡
6.88, 7.30 (4s, 3 arom. H, NH). EI-MS: 337 (87, M ), 336 (100), 309 (74), 308 (82), 280 (23), 252 (17), 237 (6).
Anal. calc. for C20H23N3O2 (337.42): C 71.20, H 6.86, N 12.45; found: C 71.51, H 6.64, N 12.17.
6. Crystal-Structure Determination of 13e (see Table 3 and Fig.)4). All measurements were performed on a
Rigaku AFC5R diffractometer with graphite-monochromated MoKa radiation (l 0.71069 ä) and a 12-kW
rotating-anode generator. The w/2q scan mode was employed for data collection. The intensities were corrected
for Lorentz and polarization effects but not for absorption. Data collection and refinement parameters are given
in Table 3, and a view of the molecule is shown in the Figure. The structure was solved by direct methods using
Table 3. Crystallographic Data of Compound 13e
Crystallized from
MeOH
Empirical formula
Formula weight [g molÀ1
Crystal color, habit
Crystal dimensions [mm]
Temp. [K]
C24H29N3O4
423.51
pale yellow, tablet
0.15 Â 0.43 Â 0.45
173(1)
]
Crystal system
Space group
triclinic
P1
≈
Z
2
Reflections for cell determination
25
2q Range for cell determination [8]
Unit-cell parameters a [ä]
37 40
12.198(2)
13.076(1)
7.308(2)
98.78(2)
106.13(2)
85.44(1)
1105.7(4)
1.272
b [ä]
c [ä]
a [8]
b [8]
g [8]
V [ä3]
Dx [gcm À3
]
m(MoKa) [mmÀ1
2q(max) [8]
]
0.0873
55
Total reflections measured
Symmetry-independent reflections
Reflections used [I > 2s(I)]
Parameters refined
5317
5077
3671
281
Final R
0.0540
0.0516
2.335
wR (w ˆ [s2(Fo) ‡ (0.005Fo)2]À1
Goodness-of-fit
)
Secondary extinction coefficient
Final Dmax/s
1.5(2) Â 10À6
0.0002
0.50; À 0.31
D1 (max; min) [e äÀ3
]
SHELXS86 [47], which revealed the position of all non-H atoms. The non-H atoms were refined anisotropically.
All of the H-atoms were fixed in geometrically calculated positions (d(CÀH) ˆ 0.95 ä), and each was assigned
a fixed isotropic displacement parameter with a value equal to 1.2 Ueq of its parent C-atom. Refinement of the
structure was carried out on F accordingto full-matrix least-squares procedures, which minimized the function
Sw(j Fo jÀj Fc j )2. A correction for secondary extinction was applied. Neutral-atom-scatteringfactors for non-H
atoms were taken from [48a] and the scatteringfactors for H-atoms from [49]. Anomalous dispersion effects
4
)
Crystallographic data (excluding structure factors) for the structure 13e reported in this paper have been
deposited with the Cambridge Crystallographic Data Centre as supplementary publication No. CCDC-
145106. Copies of the data can be obtained, free of charge, on application to the CCDC, 12 Union Road,
Cambridge CB21EZ, UK (fax: ‡44-(0)1223-336 033 or e-mail: deposit@ccdc.cam.ac.uk).

Helvetica Chimica Acta Vol. 85 (2002)
331
were included in Fc [50]; the values for f ' and f '' were those of [48b], and the values of the mass attenuation
coefficients were those of [48c]. All calculations were performed with the TEXSAN crystallographic software
package [51].
REFERENCES
[1] J. R. Geigy AG, Neth. Appl. 6,614,979, 1967 (Chem. Abstr. 1968, 68, 69003z).
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Received July 21, 2001