Synthesis and reactivity of 2-(6,7-diethoxy-3,4-dihydroisoquinolin-1-yl)acetonitrile towards hydrazonoyl halides

Article abstract of DOI:10.1002/1522-2675(20010516)84:5<1172::AID-HLCA1172>3.0.CO;2-X

The synthesis of 2-(6,7-diethoxy-3,4-dihydroisoquinolin-1-yl)acetonitrile (1) has been performed by ring closure of the corresponding amide according to the Bischler-Napieralski method (Scheme 1). Based on spectroscopic data, the tautomeric 2-(tetrahydroisoquinolin-1-ylidene)acetonitrile is the actual compound. The reactions of 1 with α-oxohydrazonoyl halides 4 in the presence of Et₃N led to 2-(aryldiazenyl)pyrrolo[2,1-a]-isoquinoline derivatives 8 (Scheme 2), whereas with C-(ethoxycarbonyl)hydrazonoyl chlorides 14, 2-(arylhydrazono)pyrrolo[2,1-a]isoquinoline-1-carbonitriles 16 were formed (Scheme 4). The structures of the products were established from their analytical and spectroscopic data and, in the case of 8b, by X-ray crystallography.

Full text of DOI:10.1002/1522-2675(20010516)84:5<1172::AID-HLCA1172>3.0.CO;2-X

1172
Helvetica Chimica Acta ± Vol. 84 (2001)
Synthesis and Reactivity of 2-(6,7-Diethoxy-3,4-dihydroisoquinolin-
1-yl)acetonitrile towards Hydrazonoyl Halides
by Enas M. Awad1)2), Nehal M. Elwan, and Hamdi M. Hassaneen*
Department of Chemistry, Faculty of Science, Cairo University, Giza
and Anthony Linden and Heinz Heimgartner*
Organisch-chemisches Institut der Universität Zürich, Winterthurerstrasse 190, CH-8057 Zürich
The synthesis of 2-(6,7-diethoxy-3,4-dihydroisoquinolin-1-yl)acetonitrile (1) has been performed by ring
closure of the corresponding amide according to the Bischler-Napieralski method (Scheme 1). Based on
spectroscopic data, the tautomeric 2-(tetrahydroisoquinolin-1-ylidene)acetonitrile is the actual compound. The
reactions of 1 with a-oxohydrazonoyl halides 4 in the presence of Et3N led to 2-(aryldiazenyl)pyrrolo[2,1-a]-
isoquinoline derivatives 8 (Scheme 2), whereas with C-(ethoxycarbonyl)hydrazonoyl chlorides 14, 2-(arylhy-
drazono)pyrrolo[2,1-a]isoquinoline-1-carbonitriles 16 were formed (Scheme 4). The structures of the products
were established from their analytical and spectroscopic data and, in the case of 8b, by X-ray crystallography.
Introduction. ± Fused isoquinoline derivatives compose a very interesting class of
compounds because of their significant biological and pharmaceutical activities [1 ± 3].
As part of our studies aimed at developing simple and efficient syntheses of
polyfunctional heteroaromatics from readily obtained starting materials, we have
previously reported the synthesis of triazoloisoquinolines and pyrroloisoquinolines
from 3,4-dihydroisoquinolines and hydrazonoyl halides [4][5]. However, in many
cases, the exact structure of the reaction products could not be established
unequivocally, because several closely similar isomeric products could be formed (cf.
[5]). Whereas 1-unsubstituted and 3,4-dihydro-1-methylisoquinolines in the presence
of Et3N reacted with a-oxo hydrazonoyl halides to give [1,2,4]triazolo[3,4-a]isoquino-
lines [5] via a 1,3-dipolar cycloaddition of the in situ generated nitrile imines (cf. [6] and
refs. cit. therein), the reaction course of the 1-cyanomethyl derivative (2-(3,4-
dihydroisoquinolin-1-yl)acetonitrile) was obviously quite different.
In the present paper, we report on the investigation of the latter reaction and the
elucidation of the structures of the products by spectroscopy and X-ray crystallography.
Results and Discussion. ± The starting material 2-(6,7-diethoxy-3,4-dihydroisoqui-
nolin-1-yl)acetonitrile (1) was prepared as shown in Scheme 1 in analogy to [7]: ring
closure of 2-cyano-N-[2-(3,4-diethoxyphenyl)ethyl]acetamide (2), prepared by heat-
ing equimolar amounts of ethyl cyanoacetate and 2-(3,4-diethoxyphenyl)ethylamine
(3) with POCl3 in CHCl3 according to the Bischler-Napieralski method [8], led to 1 in
80% yield. The structure of 1 was established on the basis of its elemental analysis and
1
)
)
Part of the Ph.D. thesis of E.M.A., Cairo University, 2001. Present address: National Research Centre,
Tahrir Street, Dokki, Giza, Egypt.
Swiss Federal scholar (Bundesstipendiatin) at the University of Zürich, October 1998 ± June 2000.
2

Helvetica Chimica Acta ± Vol. 84 (2001)
1173
Scheme 1
EtO
EtO
EtO
NH
+
NCCH2COOEt
NH2
EtO
O
NC
3
2
EtO
EtO
EtO
EtO
POCl3
NH
CN
N
CN
1B
1A
spectroscopic data. For example, the EI-MS showed an intense molecular-ion peak at
1
m/z 258. The IR spectrum (KBr) revealed the CꢀN absorption at 2167 cm , indicating
a conjugated CꢀN group. In addition, an absorption for NH appeared at 3348 cm 1 in
1
accordance with the enamine structure 1B. The H-NMR spectrum confirmed the
existence of the enamine tautomer in CDCl3 solution; it showed a singlet at 4.23 ppm
for ˆCH and a second one at 5.64 ppm for NH. The latter disappeared on shaking the
solution with D2O.
The reaction of 1 with a-oxohydrazonoyl halides 4 in refluxing THF in the presence
of Et3N afforded, in each case, a single product as evidenced by TLC analysis. Based on
the general reactivity of 1A/1B towards 4 and the corresponding nitrile imines 5,
respectively, there are four possible products 6 ± 9 (Scheme 2, cf. [5]).
Scheme 2
X
EtO
EtO
Et3N
R
CO
C
R CO
C
N
Ar
N
+
N
N
NHAr
CN
4 (X = Cl, Br)
5
1
EtO
EtO
EtO
EtO
EtO
EtO
NH
EtO
NC
O
Ar
N
N
N
N
R
NAr
N
R
N
EtO
R
N
NC
Ar
N
N
NC
NAr
NC
R
O
6
7
8
9
R / Ar
R / Ar
a
e
Me / Ph
2-thienyl / Ph
b
c
Me / 4-MeC6H4
Ph / Ph
f
g
2-naphthyl / Ph
2-naphthyl / 4-MeC6H4
d
Ph / 4-MeC6H4

1174
Helvetica Chimica Acta ± Vol. 84 (2001)
The cycloadducts 6 and 7, which could be formed via 1,3-dipolar cycloadditions of 5
with 1A and 1B, respectively (cf. [9]), were ruled out on the basis of elemental analysis
and the mass spectra of the products, which proved the loss of H2O. Furthermore, the
1
IR spectra showed the presence of a conjugated CꢀN group (2208 ± 2196 cm ) and the
absence of a CˆO group. All data were in agreement with structures 8 and 9, which are
cyclocondensation products. The electronic absorption spectra were characterized by
three maxima at 420 ± 390, 340 ± 320, and 255 ± 240 nm, corresponding to the NˆN
chromophore [10]. Unfortunately, despite all these data, one cannot distinguish
between the isomeric structures 8 and 9.
Two mechanistic pathways A and B that account for the formation of 8 and 9,
respectively, are proposed in Scheme 3. In route A, the reaction involves an initial
nucleophilic substitution of the halide of 4 by the enamine C-atom of 1B to give
intermediate 10, which is in equilibrium with the tautomer 11. Alternatively, 1B reacts
Scheme 3
EtO
EtO
NH
N
EtO
EtO
CN
CN
1B
1A
+ 4, Et3N
+ 4, Et3N
Path A
Path B
EtO
EtO
N NHAr
O
C
NH
N
O
EtO
EtO
C
C
C
N
R
NC
NC
R
NHAr
10
12
EtO
EtO
EtO
EtO
NH
N
NAr
OH
N
C
C
C
R
C
N
NC
NC
HO
R
NAr
11
- H2O
13
- H2O
EtO
EtO
EtO
EtO
N
N
R
NAr
N
R
NC
NAr
N
NC
8
9

Helvetica Chimica Acta ± Vol. 84 (2001)
1175
with nitrile imine 5 via protonation and nucleophilic addition (1,3 addition with 1,3-
dipoles, cf. [6][11 ± 14]) to give 10. Then, cyclization via elimination of H2O affords 8. In
route B, the corresponding nucleophilic substitution/addition occurs at the imine
N-atom of 1A, leading to 12 and 13 and, via elimination of H2O, to the isomeric
compound 9.
In the case of the reaction of 1 with 4b (R ˆ Me, Arˆ 4-MeC6H4, X ˆ Cl), the
structure of the orange product has been established by X-ray crystallography to be 8b
(Fig.). In the structure, the Et group of the EtO substituent at C(9)3) is disordered over
two approximately equally occupied orientations. The central fused six-membered ring
shows a screw-boat conformation. All other rings are planar. The torsion angle between
the azo group and both the pyrrole and toluene rings is ca. 98.
Figure. ORTEP Plot [15] of the molecular structure of 8b: disordered conformation A (arbitrary numbering of
the atoms; 50% probability ellipsoids)
Next, we studied the reaction between 1 and ethyl 2-(arylhydrazono)-2-chloro-
acetates 14a ± e. Treatment of 1 with 14a (Arˆ Ph) in THF in the presence of Et3N
under reflux afforded a single product 16a in 80% yield. The same product was
obtained from 1 and methyl 2-chloro-2-(phenylhydrazono)acetate (17a) under similar
conditions and by stirring equimolar amounts of 1 and 14a in ethanolic EtONa solution
at room temperature. The structure of the isolated product was assigned to be 8,9-
diethoxy-5,6-dihydro-3-oxo-2-(phenylhydrazono)pyrrolo[2,1-a]isoquinoline-1-carbo-
nitrile (16a; Scheme 4) on the basis of its elemental analysis and spectroscopic data.
3
)
Arbitrary numbering of the atoms according to the Figure.

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Helvetica Chimica Acta ± Vol. 84 (2001)
Scheme 4
Cl
N
EtO
EtO
Et3N
- HCl
EtOCO
C
+
NH
CN
NHAr
14
1B
EtO
EtO
EtO
EtO
NH
N
OEt
O
N
N
- EtOH
NC
O
NC
NHAr
NHAr
15
16
Cl
Et3N
1B
MeOCO
C
+
- HCl, - MeOH
N NHAr
17
Ar
Ph
4-MeC6H4
Ar
a
b
c
d
e
4-ClC6H4
4-NO2C6H4
4-MeOC6H4
Analysis and CI-MS indicated its molecular formula as C23H22N4O3, i.e., a condensation
1
product has been formed by elimination of HCl and EtOH. The H-NMR spectrum
revealed the absence of signals characteristic for the EtOCO group, and there was no
1
absorption due to an ester CˆO group (ca. 1735 cm ) in the IR spectrum (KBr).
1
Rather it showed two absorption bands at 2206 and 1674 cm , which can be assigned to
the conjugated CN and the lactam groups, respectively.
Similarly, the ethyl 2-(arylhydrazono)-2-chloroacetates 14b ± e reacted with 1 to
give the corresponding pyrrolo[2,1-a]isoquinolin-3-ones 16b ± e in excellent yield. The
proposed reaction mechanism (Scheme 4) that seems to account for the formation of 16
is analogous to path A in Scheme 3. Nucleophilic substitution of chloride in 14 by the
enamine C-atom of 1B (or nucleophilic addition onto the corresponding nitrile imine)
gives 15, which undergoes ring closure by elimination of EtOH to afford 16.
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.
Experimental Part
1. General. M.p.: Gallenkamp melting-point apparatus; uncorrected. UV/VIS spectra: Perkin-Elmer
Lambda 4B spectrometer. IR spectra: Pye Unicam SP-300 IR spectrophotometer and Testscan Shimadzu FTIR
1
8000 series; in KBr; nÄ in cm
.
1H-NMR spectra: Varian Gemini (200 MHz) and Varian EM (390 MHz)
instruments; in CDCl3 with TMS as an internal standard; chemical shifts d in ppm, coupling constants J in Hz.
EI-MS: GCMS-QP 1000-EX Shimadzu instrument; 70 eV. Elemental analyses were carried out at the Center of
Microanalysis, Cairo University, Giza. The X-ray crystallographic analysis was carried out at the University of
Zürich. Compounds 4a,b (chlorides) [16], 4c,d (bromides) [17], 4e (chloride) [18], 4f,g (chlorides) [19], 13a ± c

Helvetica Chimica Acta ± Vol. 84 (2001)
1177
(chlorides) [20], 13d,e (chlorides) [21], and 16a (chloride) [22] were prepared according to the reported
procedures.
2. Synthesis of 2-(6,7-Diethoxy-3,4-dihydroisoquinolin-1-yl)acetonitrile (1). A mixture of 2-(3,4-diethoxy-
phenyl)ethylamine (3; 20.9 g, 100 mmol) and ethyl cyanoacetate (11.3 g, 100 mmol) was refluxed for 3 h. The
mixture was cooled to r.t., at which it solidified. The solid was washed with EtOH and crystallized from EtOH to
give 2-cyano-N-[2-(3,4-diethoxyphenyl)ethyl]acetamide (2). The latter product was cyclized to give 1 by the
Bischler-Napieralski method [8]: 20.7 g (80%) of 1. M.p.: 1678. IR: 3348 (NH), 2167 (CN). 1H-NMR: 1.32 ± 1.52
(m, 2 Me); 2.75 ± 2.89 (m, CH2); 3.30 ± 3.46 (m, CH2N); 3.98 ± 4.16 (m, 2 CH2O); 4.23 (s, ˆCH ); 5.64 (s, NH);
.
‡
6.63, 7.01 (2s, 2 arom. H). EI-MS: 258 (100, M ), 230 (13), 201 (23), 173 (26), 149 (44), 91 (16), 81 (33), 69 (68),
57 (53), 55 (41). Anal. calc. for C15H18N2O2 (258.32): C 69.74, H 7.02, N 10.84; found: C 69.54, H 6.81, N 10.74.
3. Synthesis of 5,6-Dihydropyrrolo[2,1-a]isoquinoline Derivatives 8a ± g. General Procedure. To a soln. of 4
(5 mmol) and 1 (1.29 g, 5 mmol) in THF (40 ml) was added Et3N (1.4 ml, 10 mmol) at r.t. The mixture was
refluxed for 6 h, then the solvent was evaporated under reduced pressure, and the residue was triturated with
MeOH (10 ml), under which it solidified. The crude product was crystallized from DMF. The prepared
compounds 8a ± g are listed below.
8,9-Diethoxy-5,6-dihydro-3-methyl-2-(phenyldiazenyl)pyrrolo[2,1-a]isoquinoline-1-carbonitrile (8a): Yield
1.442 g (72%). M.p. 2548 (DMF). IR: 2196 (CN). 1H-NMR: 1.45 (m, 2 Me); 2.42 (s, Me); 3.01 ± 3.23 (m, CH2);
.
‡
‡
3.41 ± 3.60 (m, CH2N); 4.15 (m, 2 CH2O); 7.80 ± 8.25 (m, 7 arom. H). EI-MS: 401 (100, [M ‡ 1] ), 400 (90, M ),
371 (21), 296 (42), 240 (9), 77 (45), 51 (13). Anal. calc. for C24H24N4O2 (400.48): C 71.98, H 6.04, N 13.99; found:
C 72.30, H 6.23, N 13.82.
8,9-Diethoxy-5,6-dihydro-3-methyl-2-[(4-methylphenyl)diazenyl]pyrrolo[2,1-a]isoquinoline-1-carbonitrile
(8b): Yield 1.617 g (78%). M.p. 2598 (DMF). IR: 2200 (CN). 1H-NMR: 1.43 (t, J ˆ 7, Me); 1.51 (t, J ˆ 7, Me ) ;
2.40 (s, Me); 2.58 (s, Me); 3.01 (m, CH2); 4.00 (m, CH2N); 4.10 (q, J ˆ 7, CH2O); 4.21 (q, J ˆ 7, CH2O); 6.68 (s, 1
.
‡
‡
arom. H); 7.25 ± 7.78 (m, 4 arom. H); 7.90 (s, 1 arom. H). EI-MS: 416 (27), 415 (100, [M ‡ 1] ), 414 (3, M ), 385
(19), 358 (9), 296 (35), 239 (10), 193 (9), 91 (43), 77 (5), 65 (15). Anal. calc. for C25H26N4O2 (414.51): C 72.45, H
6.32, N 13.52; found: C 72.40, H 6.43, N 13.32.
8,9-Diethoxy-5,6-dihydro-3-phenyl-2-(phenyldiazenyl)pyrrolo[2,1-a]isoquinoline-1-carbonitrile (8c): Yield
1.804 g (78%). M.p. 2758 (DMF). IR: 2204 (CN). 1H-NMR: 1.43 (m, 2 Me); 2.40 ± 2.62 (m, CH2); 2.81 ± 3.43 (m,
.
‡
‡
CH2N); 4.18 (m, 2 CH2O); 7.01 ± 8.04 (m, 12 arom. H). EI-MS: 464 (30), 463 (100, [M ‡ 1] ), 462 (80, M ), 405
(13), 330 (18), 301 (18), 283 (11), 255 (13), 91 (15), 77 (46), 51 (12). Anal. calc. for C29H26N4O2 (462.56): C
75.31, H 5.67, N 12.11; found: C 75.13, H 5.61, N 12.32.
8,9-Diethoxy-5,6-dihydro-3-phenyl-2-[(4-methylphenyl)diazenyl]pyrrolo[2,1-a]isoquinoline-1-carbonitrile
(8d): Yield 1.787 g (75%). M.p. 2758 (DMF). R: 2198 (CN). 1H-NMR: 1.45 (m, 2 Me); 2.53 (s, Me); 2.81 ± 3.03
(m, CH2); 3.22 ± 3.44 (m, CH2N); 4.18 (m, 2 CH2O); 7.11 ± 8.04 (m, 11 arom. H). EI-MS: 478 (32), 477 (100,
.
‡
‡
[M ‡ 1] ), 476 (33, M ), 463 (17), 447 (13), 420 (11), 358 (13), 301 (14), 273 (13), 255 (11), 243 (10), 91 (46),
77 (10), 65 (16), 51 (5). Anal. calc. for C30H28N4O2 (476.58): C 75.61, H 5.92, N 11.76; found: C 75.34, H 5.65, N
11.48.
8,9-Diethoxy-5,6-dihydro-2-(phenyldiazenyl)-3-(2-thienyl)pyrrolo[2,1-a]isoquinoline-1-carbonitrile (8e):
.
‡
‡
Yield 1.898 g (81%). M.p. 2438 (DMF). IR: 2208 (CN). EI-MS: 469 (100, [M ‡ 1] ), 468 (91, M ), 440
(14), 439 (6), 412 (10), 363 (15), 307 (10), 280 (6), 261 (7), 77 (44), 51 (10). Anal. calc. for C27H24N4O2S
(468.58): C 69.21, H 5.16, N 11.96, S 6.84; found: C 69.18, H 5.32, N 11.68, S 6.63.
8,9-Diethoxy-5,6-dihydro-3-(naphthalen-2-yl)-2-(phenyldiazenyl)pyrrolo[2,1-a]isoquinoline-1-carbonitrile
.
‡
‡
(8f): Yield 1.922 g (75%). M.p. 2828 (DMF). IR: 2208 (CN). EI-MS: 513 (37, [M ‡ 1] ), 512 (100, M ), 483
(10), 455 (21), 407 (14), 362 (8), 334 (8), 322 (14), 305 (10), 293 (8), 292 (7), 77 (9). Anal. calc. for C33H28N4O2
(512.62): C 77.32, H 5.51, N 10.93; found: C 77.43, H 5.42, N 10.64.
8,9-Diethoxy-5,6-dihydro-2-[(4-methylphenyl)diazenyl]-3-(naphthalen-2-yl)pyrrolo[2,1-a]isoquinoline-1-
.
‡
carbonitrile (8g): Yield 2.159 g (82%). M.p. 2988 (DMF). IR: 2206 (CN). EI-MS: 526 (100, M ), 469 (9), 407
(17), 351 (23), 322 (29), 305 (26), 293 (22), 235 (15), 152 (7), 91 (88), 65 (21), 55 (21). Anal. calc. for
C34H30N4O2 (526.64): C 77.54, H 5.74, N 10.64; found: C 77.69, H 5.77, N 10.41.
4. Synthesis of 5,6-Dihydro-3-oxopyrrolo[2,1-a]isoquinoline-1-carbonitrile Derivatives (16a ± e). General
Procedure 1. Compounds 16 were prepared by the same method described for the synthesis of 8, but using 1 and
14 in place of 4.
General Procedure 2. To a stirred ethanolic soln. of EtONa, prepared from Na (0.1 g, 5 mmol) and abs.
EtOH (30 ml), was added 1 (1.29 g, 5 mmol). Then the appropriate hydrazono acetate 14 (5 mmol) was added
at r.t. The mixture was stirred for 1 h, during which 14 was dissolved and the crude product was precipitated. The

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Helvetica Chimica Acta ± Vol. 84 (2001)
latter was washed with H2O, dried, and crystallized from a suitable solvent. The prepared compounds 16a ± e are
listed below.
8,9-Diethoxy-5,6-dihydro-3-oxo-2-(phenylhydrazono)pyrrolo[2,1-a]isoquinoline-1-carbonitrile (16a):
Yield 1.611 g (80%). M.p. 2488 (DMF). IR: 3258 (NH), 2207 (CN), 1667 (CO). 1H-NMR: 1.34 (m, 2 Me);
3.02 (m, CH2); 3.83 (m, CH2N); 4.11 (m, 2 CH2O); 7.12 (s, 1 arom. H); 7.15 ± 7.53 (m, 5 arom. H); 7.74 (s, 1 arom.
.
‡
H); 12.64 (s, NH). EI-MS: 402 (100, M ), 374 (13), 345 (17), 317 (8), 241 (5), 77 (33), 65 (16), 51 (8). Anal.
calc. for C23H22N4O3 (402.46): C 68.64, H 5.51, N 13.92; found: C 68.50, H 5.41, N 13.72.
8,9-Diethoxy-5,6-dihydro-2-[(4-methylphenyl)hydrazono]-3-oxopyrrolo[2,1-a]isoquinoline-1-carbonitrile
(16b): Yield 1.688 g (81%). M.p. 2458 (DMF). IR: 3363 (NH), 2211 (CN), 1670 (CO). 1H-NMR: 1.34 (m,
2 Me); 2.34 (s, Me); 3.03 (m, CH2); 3.82 (m, CH2N); 4.14 (m, 2 CH2O); 7.11 (s, 1 arom. H); 7.20 ± 7.43 (m, 4
.
‡
arom. H); 7.74 (s, 1 arom. H); 12.61 (s, NH). EI-MS: 416 (100, M ), 359 (14), 282 (15), 194 (6), 180 (9), 106
(39), 91 (45), 77 (18), 55 (15). Anal. calc. for C24H24N4O3 (416.48): C 69.22, H 5.80, N 13.45; found: C 69.01, H
5.73, N 13.22.
8,9-Diethoxy-5,6-dihydro-2-[(4-methoxyphenyl)hydrazono)]-3-oxopyrrolo[2,1-a]isoquinoline-1-carboni-
trile (16c): Yield 1.688 g (78%). M.p. 2538 (DMF). IR: 3286 (NH), 2205 (CN), 1676 (CO). 1H-NMR: 1.49 (t,
J ˆ 7, Me); 1.53 (t, J ˆ 7, Me); 3.00 (m, CH2); 3.82 (s, MeO); 3.90 (m, CH2N); 4.13 (q, J ˆ 7, CH2O); 4.21 (q, J ˆ 7,
CH2O); 6.71 (s, 1 arom. H); 6.86 ± 7.40 (m, 4 arom. H); 7.85 (s, 1 arom. H); 12.75 (s, NH). EI-MS: 434 (5), 433
.
‡
‡
(35, [M ‡ 1] ), 432 (100, M ), 122 (5). Anal. calc. for C24H24N4O4 (432.48): C 66.65, H 5.59, N 12.96; found: C
66.60, H 5.32, N 12.71.
2-[(4-Chlorophenyl)hydrazono]-8,9-diethoxy-5,6-dihydro-3-oxopyrrolo[2,1-a]isoquinoline-1-carbonitrile
(16d): Yield 1.638 g (75%). M.p. 2608 (DMF). IR: 3315 (NH), 2202 (CN), 1685 (CO). EI-MS: 439 (35), 438
.
‡
‡
(29, [M ‡ 1] ), 437 (100, M ), 408 (21), 379 (19), 35 (6), 241 (6), 213 (5), 128 (7), 111 (22), 99 (13), 77 (5).
Anal. calc. for C23H21N4O3Cl (436.90): C 63.23, H 4.85, N 12.82; found: C 63.52, H 4.56, N 12.61.
8,9-Diethoxy-5,6-dihydro-2-[(4-nitrophenyl)hydrazono]-3-oxopyrrolo[2,1-a]isoquinoline-1-carbonitrile
(16e): Yield 1.790 g (80%). M.p. 2788 (DMF). IR: 3280 (NH), 2206 (CN), 1681 (CO). 1H-NMR: 1.44 (m,
2 Me); 3.02 (m, CH2); 3.83 (m, CH2N); 4.12 (m, 2 CH2O); 7.14 (s, 1 arom. H); 7.53 (s, 1 arom. H); 7.71 ± 8.20 (m,
.
‡
‡
4 arom. H); 12.62 (s, NH). EI-MS: 449 (28), 448 (100, [M ‡ 1] ), 447 (72, M ), 390 (21). Anal. calc. for
C23H21N5O5 (447.46): C 61.74, H 4.73, N 15.65; found: C 61.51, H 4.52, N 15.40.
5. Crystal-Structure Determination of 8b (see Table and Fig.)4). All measurements were made on a Rigaku
AFC5R diffractometer with graphite-monochromated MoKa radiation (l 0.71069 Š) 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
the Table, and a view of the molecule is shown in the Figure. The structure was solved by direct methods with
SHELXS97 [23], which revealed the position of all non-H-atoms. The Et group of one EtO substituent is
disordered over two orientations. Two sets of atoms for this Et group were defined and their site occupation
factors were initially refined, then held fixed at a ratio of 0.574 :0.426. The non-H-atoms were refined
anisotropically. All of the H-atoms were fixed in geometrically calculated positions 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 by means of full-matrix least-squares procedures, which minimized the function
Sw j Fo j j Fc j )2. A correction for secondary extinction was applied. Neutral-atom-scattering factors for non-H-
atoms were taken from [24a] and the scattering factors for H-atoms from [25]. Anomalous dispersion effects
were included in Fc [26]; the values for f ' and f '' were those of [24b], and the values of the mass-attenuation
coefficients were those of [24c]. All calculations were performed with the teXsan crystallographic software
package [27].
4
)
Crystallographic data (excluding structure factors) for the structure 8b reported in this paper have been
deposited with the Cambridge Crystallographic Data Centre as supplementary publication Nr. CCDC-
145107. Copies of the data can be obtained, free of charge, on application to the CCDC, 12 Union Road,
Cambridge CB21EZ, UK (fax: ‡44-(0)1223-336033 or e-mail: deposit@ccdc.cam.ac.uk).

Helvetica Chimica Acta ± Vol. 84 (2001)
1179
Table 1. Crystallographic Data of Compound 8b
Crystallized from
DMF
Empirical formula
Formula weight [gmol
Crystal color, habit
Crystal dimensions [mm]
Temp. [K]
Crystal system
Space group
Z
C25H26N4O2
414.51
1
]
orange, plate
0.13 Â 0.40 Â 0.40
233(1)
monoclinic
C2/c
8
Reflections for cell determination
25
2q Range for cell determination [8]
Unit-cell parameters a [Š]
33 ± 40
32.563(2)
7.425(8)
18.394(1)
98.972(6)
4392(4)
1.254
b [Š]
c [Š]
b [8]
V [Š3]
3
Dx [gcm
]
1
m(MoKa) [mm
2q(max) [8]
]
0.0814
55
Total reflections measured
Symmetry-independent reflections
Reflections used [I > 2s(I)]
Parameters refined
5532
5042
2617
299
Final R
0.0514
0.0444
1.643
1
wR (w ˆ [s2(Fo) ‡ (0.005Fo)2]
)
Goodness-of-fit
7
Secondary extinction coefficient
2.1(1) Â 10
Final Dmax/s
D1 (max; min) [e Š
0.0002
3
]
0.19; 0.16
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Received March 3, 2001