Reactivity of ethyl 1,2,3,4-tetrahydro-6,7-dimethoxy-1-isoquinolylidene acetate towards nitrilimines. Synthesis of pyrrolo[2,1-a]-5,6-dihydroisoquinoline

Article abstract of DOI:10.1081/SCC-120003395

Hydrazonoyl halides 3 and 8 react with 3,4-dihydro-6,7-dimethoxyisoquinoline-1-methyleneethoxycarbonyl 2 to give ethyl 2-(1,2,3,4-tetrahydro-6,7-dimethoxyisoquinoline-1-ylidene)-2-(N-phenyl-N ′-benzylidene-hydrazine) acetate 7 and pyrrolo[2,1-a]5,6-dihydroisoquinoline 13 respectively. Structures of the new compounds were elucidated on the basis of elemental analysis, spectral data (IR, ¹H NMR, MS).

Full text of DOI:10.1081/SCC-120003395

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REACTIVITY OF ETHYL 1,2,3,4-TETRAHYDRO-6,7-
DIMETHOXY-1-ISOQUINOLYLIDENE ACETATE TOWARDS
NITRILIMINES. SYNTHESIS OF PYRROLO[2,1-a]-5,6-
DIHYDROISOQUINOLINE
Tayseer A. Abdallah a
a Department of Chemistry , Faculty of Science , Cairo University , Giza, 12613, Egypt
Published online: 16 Aug 2006.
To cite this article: Tayseer A. Abdallah (2002) REACTIVITY OF ETHYL 1,2,3,4-TETRAHYDRO-6,7-DIMETHOXY-1-
ISOQUINOLYLIDENE ACETATE TOWARDS NITRILIMINES. SYNTHESIS OF PYRROLO[2,1-a]-5,6-DIHYDROISOQUINOLINE, Synthetic
Communications: An International Journal for Rapid Communication of Synthetic Organic Chemistry, 32:16, 2459-2465, DOI:
10.1081/SCC-120003395
To link to this article: http://dx.doi.org/10.1081/SCC-120003395
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SYNTHETIC COMMUNICATIONS
Vol. 32, No. 16, pp. 2459–2465, 2002
REACTIVITY OF ETHYL 1,2,3,4-
TETRAHYDRO-6,7-DIMETHOXY-1-
ISOQUINOLYLIDENE ACETATE
TOWARDS NITRILIMINES. SYNTHESIS
OF PYRROLO[2,1-a]-5,6-
DIHYDROISOQUINOLINE
Tayseer A. Abdallah
Department of Chemistry, Faculty of Science,
Cairo University, Giza 12613, Egypt
E-mail: tiseer123@hotmail.com
ABSTRACT
Hydrazonoyl halides 3 and 8 react with 3,4-dihydro-6,7-
dimethoxyisoquinoline-1-methyleneethoxycarbonyl 2 to give
ethyl 2-(1,2,3,4-tetrahydro-6,7-dimethoxyisoquinoline-1-ylid-
ene)-2-(N-phenyl-N0-benzylidene-hydrazine) acetate 7 and pyr-
rolo[2,1-a]5,6-dihydroisoquinoline 13 respectively. Structures
of the new compounds were elucidated on the basis
of elemental analysis, spectral data (IR, 1H NMR, MS).
In continuation of our previous work on the use of isoquinoline
derivatives for the synthesis of heterocyclic compounds.[1–3] I wish to
report the synthesis of pyrrolo[2,1-a]dihydroisoquinoline derivatives. Such
ring systems have a considerable pharmacological activities as cardiovascu-
larly,[4] antiflammatory[5] and antidepressant.[6] Also, I study the effect of
2459
DOI: 10.1081/SCC-120003395
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2460
ABDALLAH
the presence of the carbonyl group in ꢀ-ketohydrazonoyl halide on the
course of the reaction.
RESULTS AND DISCUSSION
The starting material 2 was prepared by esterification of 1 in absolute
ethanol as previously described.[7] Its 1H NMR spectrum confirmed the
enamine form 2A (Scheme 1). It shows signals at ꢁ 1.5 (t, 3H), 2.8 (t, 2H),
3.4 (t, 2H), 3.8 (s, 3H), 3.9 (s, 3H), 4.2 (q, 2H), 5.0 (s, 1H), 6.7 (s, 1H), 7.1
(s, 1H), 9.0 (s, 1H, NH).
Reaction of 3,4-dihydro-6,7-dimethoxyisoquinoline-1-methyleneethoxy-
carbonyl 2 with diphenylnitrilimine, generated in situ by the reaction of
triethylamine on the N-phenylbenzohydrazonoyl chloride 3 in refluxing
chloroform, yielded a product whose elemental analysis was compatible
with the amidrazone structure 4, the hydrazone 5 or the rearranged product
7 resulting from the spiro compound 6 (Scheme 2).
Although amidrazone of type 4 is known to be stable[8–10] all attempts
made to separate it from the reaction mixture were failed. The substitution
1
product 5 was rejected on the basis of its H NMR and IR spectrum. The
IR spectrum of 5 reveals two NH stretching vibrations which not appear in
the IR spectrum of the product. The structure of compound 7 was confirmed
1
1
on the basis of H NMR and 13C NMR spectra. Thus H NMR spectrum
shows a signal at ꢁ 8.1 corresponding to the methine CH-proton of the
hydrazone moiety.[11,12]
Next, the effect of carbonyl group in ꢀ-ketohydrazonoyl halides
on the course of their reaction with 2 was investigated. Treatment of 2
Scheme 1.

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PYRROLO[2,1-a]-5,6-DIHYDROISOQUINOLINE
2461
Scheme 2.
with ꢀ-ketohydrazonoyl halides 8 in refluxing chloroform in the presence of
triethylamine leads to the formation of 13. In all cases, only one product was
1
formed as shown by TLC and H NMR of the crude reaction mixture. The
isolated products 13 gave satisfactory elemental analyses and
1
spectroscopic data (IR, H NMR, MS) for the proposed structures. For
example, the IR spectra of all the products isolated from the reaction of
8 with 2 showed a characteristic carbonyl absorption band for ethoxycar-
bonyl group near 1700 cmÀ1
.
The 1H NMR spectra of all compounds showed a triplet signal at ꢁ 1.4
and quartet signal at ꢁ 4.4 corresponds to ethoxycarbonyl group in 13.
The mass spectra of all compounds exhibit a molecular ion peak with
high intensity. The electronic absorption spectra of the resulting products
are characterised by four intense maxima at ꢂ near 480, 410, 330 and 250 nm
assignable to azo chromophore.[13]
Also, 13C-NMR of compound 13a taken as a typical example illus-
trates the signals that confirm the structure 13. On the basis of the above

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2462
ABDALLAH
data, the products isolated from reaction of 8 with 2 were assigned structure
13 and not the amidrazone 9 or the cycloadduct 10. The reaction pathway
that seems to account for the formation of 13 from 8 and 2 is outlined
in Scheme 3. It is proposed that the reaction involves initial nucleophilic
substitution to give 11, which cyclized via elimination of the elements of
water to give 13.
Scheme 3.

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PYRROLO[2,1-a]-5,6-DIHYDROISOQUINOLINE
2463
EXPERIMENTAL
Melting points were taken on a Gallenkamp apparatus and are uncor-
rected. Infrared spectra (KBr) were determined on a Pye Unicam SP-3000
infrared spectrophotometer. The NMR spectra in CDCl3 were recorded
on a Varian Gemini 200 instrument (1H NMR 200 MHz) with TMS as the
internal standard. Elemental analyses were carried out at the Microanaly-
tical center, University of Cairo, Giza, Egypt. Hydrazonoyl halides 3,[14]
8a,b[15], 8c,d[16], 8e,f[17], 8g,h.[18]
Synthesis of ethyl 2-(1,2,3,4-tetrahydro-6,7-dimethoxyisoquinoline-1-
ylidene)-2-(N-phenyl-N0-benzylidenehydrazine)acetate 7: To a solution of
hydrazonoyl halide 3 (5 mmol) and 3,4-dihydro-6,7-dimethoxyisoquino-
line-1-methyleneethoxycarbonyl 2 (1.38 g, 5 mmol) in chloroform (40 mL)
was added triethylamine (1.4 mL, 10 mmol) at room temperature. The
reaction mixture was refluxed for 6 h. The solvent was evaporated under
reduced pressure and the residue was triturated with methanol (10 mL)
where it solidified. The crude product was collected and crystallised
from dimethylformamide-ethanol mixture to give the corresponding ethyl
2-(1,2,3,4-tetrahydro-6,7-dimethoxyisoquinoline-1-ylidene)-2-(N-phenyl-N0-
benzylidenehydrazine) acetate 7. The compound prepared with its physical
constants are given below. 7: m.p. 170ꢀC; 80% yield; ꢃmax/cmÀ1 (KBr) 1640
(C¼O); ꢁH (CDCl3) 1.1 (t, J ¼ 7Hz, 3H), 3.4 (m, 2H), 3.5 (s, 3H), 3.8 (s, 3H),
4.0 (m, 2H), 4.1 (q, J ¼ 7Hz, 2H), 6.8 (s, 1H), 7.1 (s, 1H), 7.1–8.1 (m, 10H),
10.5 (s, 1H); 13C (CDCl3) (APT pulse sequence) ꢁ 16.30, 31.10, 40.75,
57.47, 57.55, 61.14, 82.71, 112.054, 113.27, 115.02, 121.67, 122.71, 127.89,
129.37, 130.11, 131.25, 132.94, 141.91, 145.35, 147.13, 149.30, 152.82,
160.65, 172.0; m/z 471; (Found: C, 71.2; H, 5.9; N, 8.8. C28H29N3O4 requires
C, 71.3; H, 6.1; N, 8.9%).
Synthesis of pyrrolo[2,1-a]-5,6-dihydroisoquinoline 13: These com-
pounds were prepared by the same method described for the synthesis of
7 using hydrazonoyl halide 8 in place of 3 to give 13. The compounds
prepared with their physical constants are given below. 13a: m.p. 187ꢀC;
82% yield; ꢃmax/cmÀ1 (KBr) 1693 (C¼O); ꢁH (CDCl3) 1.3 (t, J ¼ 7 Hz, 3H),
2.6 (s, 3H), 3.0 (m, 2H), 3.9 (s, 3H), 4.0 (s, 3H), 4.0 (m, 2H), 4.3 (q, J ¼ 7 Hz,
2H), 6.7 (s, 1H), 7.4 (s, 1H), 7.4–7.8 (m, 5H); 13C (CDCl3) (APT
pulse sequence) ꢁ 9.25, 14.14, 28.45, 40.72, 55.86, 55.92, 61.14, 108.14,
111.08, 122.08, 122.22, 125.15, 128.76, 128.99, 129.19, 133.46, 148.50,
148.65, 153.43, 168.96, 181.06; m/z 419; (Found: C, 68.8; H, 5.6;
N, 9.8.C24H25 N3O4 requires C, 68.7; H, 5.9; N, 10.0%). 13b: m.p. 188ꢀC;
80% yield; ꢃmax/cmÀ1 (KBr) 1714 (C¼O); ꢁH (CDCl3) 1.2 (t, J ¼ 7Hz, 3H),
2.3 (s, 3H), 2.5 (s, 3H), 3.3 (m, 2H), 3.8 (s, 3H), 3.9 (s, 3H), 3.9 (m, 2H),
4.3 (q, J ¼ 7Hz, 2H), 6.5 (s, 1H), 7.0 (s, 1H), 7.2–7.7 (m, 4H), m/z

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2464
ABDALLAH
433; (Found: C, 69.0; H, 6.1; N, 9.5. C25H27N3O4 requires C, 69.2; H,
6.2; N, 9.6%). 13c: m.p. 214ꢀC; 78% yield; ꢃmax/cmÀ1 (KBr) 1718 (C¼O);
ꢁH (CDCl3) 1.3 (t, J ¼ 7 Hz, 3H), 3.0 (m, 2H), 3.9 (s, 3H), 4.0 (s, 3H), 4.1
(m, 2H), 4.4 (q, J ¼ 7Hz, 2H), 6.7 (s, 1H), 7.3 (s, 1H), 7.3–7.7 (m, 10H); m/z
481; (Found: C, 72.6; H, 5.4; N, 8.5. C29H27N3O4 requires C, 72.3; H, 5.6;
N, 8.7%). 13d: m.p. 220ꢀC; 81% yield; ꢃmax/cmÀ1 (KBr) 1710 (C¼O);
ꢁH (CDCl3) 1.4 (t, J ¼ 7 Hz, 3H), 2.4 (s, 3H), 3.0 (m, 2H), 3.9 (s, 3H), 4.0
(s, 3H), 4.0 (m, 2H), 4.4 (q, J ¼ 7Hz, 2H), 6.7 (s, 1H), 7.1 (s, 1H), 7.2–7.7
(m, 9H); m/z 495; (Found: C, 72.5; H, 5.6; N, 8.1. C30H29N3O4 requires C,
72.7; H, 5.8; N, 8.4%. 13e: m.p. 271ꢀC; 79% yield; ꢃmax/cmÀ1 1708 (C¼O);
ꢁH (CDCl3) 1.3 (t, J ¼ 7Hz, 3H), 3.0 (m, 2H), 3.9 (s, 3H), 4.0 (s, 3H), 4.2 (m,
2H), 4.4 (q, J ¼ 7 Hz, 2H), 6.7 (s, 1H), 7.3 (s, 1H), 7.3–8.1 (m, 12H); m/z 531;
(Found: C, 74.6; H, 5.6; N, 7.8. C33H29N3O4 requires C, 74.6; H, 5.5, N,
7.9%). 13f: m.p. 218ꢀC; 80% yield; ꢃmax/cmÀ1 (KBr) 1706 (C¼O); ꢁH
(CDCl3) 1.3 (t, J ¼ 7 Hz, 3H), 2.3 (s, 3H), 3.0 (m, 2H), 3.9 (s, 3H), 4.0
(s, 3H), 4.1 (m, 2H), 4.4 (q, J ¼ 7 Hz, 2H), 6.7 (s, 1H), 7.2 (s, 1H), 7.2–8.1
(m, 11H); m/z 545; (Found: C, 74.7; H, 5.6; N, 7.5. C34H31N3O4 requires
74.8; H, 5.6; N, 7.7%). 13g: m.p. 159ꢀC; 81% yield; ꢃmax/cmÀ1 (KBr)
1713 (C¼O); ꢁH (CDCl3) 1.3 (t, J ¼ 7 Hz 3H), 3.0 (m, 2H), 3.9 (s, 3H),
4.0 (s, 3H), 4.2 (m, 2H), 4.4 (q, J ¼ 7 Hz, 2H), 6.7 (s, 1H), 7.2 (s, 1H),
7.2–7.8 (m, 8H), m/z 487; (Found: C, 66.6; H, 5.3; N, 8.6; S, 6.7.
C27H25N3O4S requires C, 66.5; H, 5.1; N, 8.6; S, 6.5%). 13h: m.p. 210ꢀC;
78% yield; ꢃmax/cmÀ1 (KBr) 1701 (C¼O); ꢁH (CDCl3) 1.3 (t, J ¼ 7 Hz, 3H),
2.4 (s, 3H), 3.0 (m, 2H), 3.9 (s, 3H), 4.0 (s, 3H), 4.2 (m, 2H), 4.4 (q, J ¼ 7 Hz,
2H), 6.7 (s, 1H), 7.1 (s, 1H), 7.2–8.2 (m, 7H); m/z 501; (Found: C, 67.0; H,
5.1; N, 8.4; S, 6.1. C28H27N3O4S requires C, 67.0; H, 5.3; N, 8.3; S, 6.3%).
REFERENCES
1. Elwan, N.M.; Abdelhadi, H.A.; Abdallah, T.A.; Hassaneen, H.M.
Tetrahedron 1996, 52, 3451.
2. Abdelhadi, H.A.; Elwan, N.M.; Abdallah, T.A.; Hassaneen, H.M.
J. Chem. Res (s) 1996, 292.
3. Abdallah, T.A.; Abdelhadi, H.A.; Ibrahim, A.A.; Hassaneen, H.M.
Synth. Commun. 2001 (in press).
4. Geigy, J. R.; Neth pat. 1967, 66, 14979 (Chem. Abstr. 1968, 68, 95859).
5. Cavallito, C. J.; Gary, A.P.; Fr. Pat. 2135297, 1973, (Chem. Abstr. 1973,
79, 96989).
6. Maryanoff, B.E.; McComsey, D.F.; Constanzo, M.J.; Setler, P.E.;
Garddock, G.F.; Shank, R.P.; Schemeider, C.R. J. Med. Chem. 1984,
27, 946.

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PYRROLO[2,1-a]-5,6-DIHYDROISOQUINOLINE
2465
7. Osbond, J.M. J. Am. Chem. Soc. 1951, 73, 3464.
8. Hassaneen, H.M.; Mousa, H.A.H.; Abed, N.M. Heterocycles 1988,
3, 27.
9. Shawali, A.S.; Hassaneen, H.M.; Sherif, M.S. J. Heterocycl. Chem.
1980, 17, 1745.
10. Hassaneen, H.M.; Abdelhamid, A.O.; Fahmi, A.A.; Shawali, A.S.
J. Heterocycl. Chem. 1985, 22, 395.
11. Badawy, M.A.; Abdel-Hady, S.A.; Ibrahim, Y.A. Liebigs Ann. Chem.
1990, 393.
12. Badawy, M.A.; Abdel-Hady, S.A.; Kadry; A.M.; Ibrahim, Y.A. Sulfur
Letters 1989, 9, 149.
13. Salem, A.G.; Thompson, A.R. J. Chem. Soc. 1952, 4793.
14. Wolkoff, P. Can. J. Chem. 1975, 53, 1333.
15. Eweiss, N.F.; Abelhamid, A.O. J. Heterocycl. Chem. 1980, 17, 1713.
16. Shawali, A.S.; Abelhamid, A.O. Bull. Chem. Soc. Jpn. 1976, 49, 321.
17. Hassaneen, H.M.; Shawali, A.S.; Elwan, N.M.; Abounada, N.M.
Sulfur letters, 1992, 13, 273.
18. Farag, A.M.; Algharib, M.S. Org. Prep. Proced. Int. 1988, 20, 521.
Received in the UK March 28, 2001

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