Condensation of 2-Benzoyl-1-cyano-1,2-dihydroisoquinoline with Electrophilic Alkenes under Phase-transfer Catalytic (PTC) Conditions

Article abstract of DOI:10.1039/a709142g

Condensation of Reissert compound 1 with electrophilic alkenes 2 carried out in the presence of 50% aqueous sodium hydroxide and benzyltriethylammonium chloride (TEBAC) as a catalyst, affords 1-(2-substituted-ethyl)isoquinolines 3 and/or 4.

Full text of DOI:10.1039/a709142g

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262 J. CHEM. RESEARCH (S), 1998
J. Chem. Research (S),
1998, 262±263$
Condensation of 2-Benzoyl-1-cyano-1,2-
dihydroisoquinoline with Electrophilic Alkenes Under
Phase-transfer Catalytic (PTC) Conditions$
Andrzej Jonczyk* and Urszula Lorencewicz-Pakulska
Warsaw University of Technology, Faculty of Chemistry, Koszykowa 75, 00-662 Warsaw, Poland
Condensation of Reissert compound 1 with electrophilic alkenes 2 carried out in the presence of 50% aqueous sodium
hydroxide and benzyltriethylammonium chloride (TEBAC) as a catalyst, affords 1-(2-substituted-ethyl)isoquinolines 3
and/or 4.
Alkylation1,2 of 2-benzoyl-1-cyano-1,2-dihydroisoquinoline2
(isoquinoline Reissert compound) 1 and its condensation2,3
with aldehydes or ketones can be conveniently and
eciently carried out in the presence of concentrated
aqueous alkali-metal hydroxides and a quaternary am-
monium salt as a catalyst (phase-transfer catalysis, PTC4±7).
On the other hand, application of PTC for synthetically
useful reactions of nitrile 1 with electrophilic alkenes has
not been described, but these processes were conducted with
Scheme 2
PhLi in ethereal solvents8±11 or with ButOK in DMSO,12 to
give the products in good to low yield (Scheme 1).
Now we report that a simple stirring of nitrile 1, slight
excess of electrophilic alkene 2, benzyltriethylammonium
chloride (TEBAC) as a catalyst (5 mol%), and 50% aqueous
sodium hydroxide, in benzene or acetonitrile, at 20±30 8C,
resulted in the formation of products 4 or their mixtures
with 3 (Scheme 2, Tables 1 and 2).
Analysis of the crude reaction products by 1H NMR
Scheme 1
spectroscopy reveals that the use of acrylates 2a±c resulted
Table 1 Reaction of 1 with electrophilic alkenes 2
2, 3, 4
Product, yield (%)
Reaction
time/h
Entry
R
Z
3 (mp 8C)
4 (mp 8C)
1a
2a
3a
4
a, H
b, H
c, H
d, Me
e, Me
f, H
CO2Me
CO2Pri
CO2But
CO2Me
CO2Bun
CN
2.0
3.5
2.0
2.0
6.0
2.0
1.0
2.0
a, 42 (132±134)
b, 73 (71±72)
c, 44 (64±66)
Ð
Ð
Ð
Ð
Ð
ab, Ð
b, oil
c, oil
d, 56 (88±90)
e, 47 (oil)
f, 65 (89±91)
g, 53 (62±64)
h, 25 (136±137)
5
6c
7
g, Me
h, H
CN
SO2Ph
8
aRatio of 3: 4 determined by 1H NMR spectra in crude reaction mixtures: 3a: 4a13.3:1; 3b: 4b15.0:1;
3c :4c13.8:1. bAnalytical sample was not isolated. cIn MeCN, other reactions in benzene.
in the formation of mixtures of 3a±c and 4a±c in which the
*To receive any correspondence.
former prevail. Pure products 3a±c were easily isolated by
crystallization, while separation of analytical samples of 4b,
c required the use of column chromatography. Particularly
$This is a Short Paper as de®ned in the Instructions for Authors,
Section 5.0 [see J. Chem. Research (S), 1998, Issue 1]; there is there-
fore no corresponding material in J. Chem. Research (M).

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J. CHEM. RESEARCH (S), 1998 263
Table 2 Proton NMR data of products 3 and 4
Product
dH (CDCl3), J/Hz
3a
3b
3c
3.69 (s, 3 H, CH3), 4.06, 4.10 (part AB of ABX, JAB117.2, 2 H, CH2), 5.58 (part X of ABX, JAX19.0, JBX15.0, 1 H, CH),
7.45±7.82 (m, 7 H, ArH), 8.12±8.26 (m, 4 H, ArH)
1.10 and 1.12 [two d, J16.3, 6 H together, C(CH3)2], 4.05 (d, J17.1, 2 H, CH2), 4.99 (sep, J16.3, 1 H, CH), 5.50
(t, J17.1, 1 H, CH), 7.44±7.80 (m, 7 m, ArH), 8.10±8.28 (m, 4 H, ArH)
1.31 [s, 9 H, C(CH3)3], 4.00, 4.05 (part AB of ABX, JAB116.7, 2 H, CH2), 5.44 (part X of ABX, JAX17.7, JBX16.6, 1 H,
CH), 7.44±7.84 (m, 7 H, ArH), 8.10±8.28 (m, 4 H, ArH)
4aa
4b
2.96±3.04 (m, 2 H, CH2), 3.61±3.69 (m, 2 H, CH2), 3.69 (s, 3 H, CH3), ArH overlapped with those of 3a
1.19 [d, J16.3, 6 H, C(CH3)2], 2.89±2.97 (m, 2 H, CH2), 3.58±3.66 (m, 2 H, CH2), 5.02 (sep, J16.3, 1 H, CH),
7.48±7.81 (m, 4 H, ArH), 8.17 (dm, J17.8, 1 H, ArH), 8.39 (d, J15.7, 1 H, ArH)
1.41 [s, 9 H, C(CH3)3], 2.83±2.91 (m, 2 H, CH2), 3.54±3.62 (m, 2 H, CH2), 7.46±7.80 (m, 4 H, ArH), 8.16 (dm, J18.0,
1 H, ArH), 8.40 (d, J15.7, 1 H, ArH)
4c
4d
4e
1.29 (d, J16.8, CH3), 3.24±3.39 (m, 2 H, CH2), 3.36 (s, 3 H, CH3O), 3.70±3.84 (m, 1 H, CH), 7.51 (d, J15.5, 1 H,
ArH), 7.55±7.83 (m, 3 H, ArH), 8.17 (dm, J18.0, 1 H, ArH), 8.42 (d, J15.7, 1 H, ArH)
0.85 (t, J17.0, 3 H, CH3), 1.15±1.60 and 1.30 (m and d, J16.0, 7 H, CH2CH2 and CH3CH), 3.20±3.40 (m, 2 H, CH2CH),
3.65±3.85 (m, 1 H, CH), 4.03 (t, J16.6, 2 H, CH2O), 7.47 (d, J15.4, 1 H, ArH), 7.51±7.79 (m, 3 H, ArH),
8.16 (dm, J18.4, 1 H, ArH), 8.42 (d, J15.8 ArH)
4f
3.03±3.13 (m, 2 H, CH2), 3.63±3.71 (m, 2 H, CH2), 7.50±7.90 (m, 4 H, ArH), 8.09 (dm, J18.0, 1 H, ArH), 8.45
(d, J16.8, 1 H, ArH)
4g
4h
1.46 (d, J16.8, 3 H, CH3), 3.35±3.80 (m, 3 H, CH2CH), 7.57 (d, J15.6, 1 H, ArH), 7.58±7.86 (m, 3 H, ArH), 8.09
(dm, J18.4, 1 H, ArH), 8.47 (d, J15.7, 1 H, ArH)
3.80 [br s, 4 H, (CH2)2], 7.49±7.85 (m, 7 H, ArH), 7.95±8.01 (m, 2 H, ArH), 8.10 (dm, J17.9, 1 H, ArH), 8.31 (d, J15.7,
1 H, ArH)
aTaken from the spectrum of a mixture of 3a and 4a.
with benzene, the organic phases were washed with brine,
dried (MgSO4), the solvent was evaporated, and the residue was
puri®ed by column chromatography (4e) or by crystallization (4g,h).
1-(2-Butoxycarbonylpropyl)isoquinoline (4e). (Found: C, 75.28; H,
7.85; N, 5.20. C17H21NO2 requires C, 75.25; H, 7.79; N, 5.16%).
1-(2-Cyanopropyl)isoquinoline (4g). (Found: C, 79.78; H, 6.12;
N, 14.22. C13H12N2 requires C, 79.60; H, 6.12; N, 14.28%).
1-(2-Phenylsulfonylethyl)isoquinoline (4h). (Found: C, 68.16; H, 5.07;
N, 4.55. C17H15NO2S requires C, 68.66; H, 5.08; N, 4.71%).
signi®cant are the results of reaction of 1 with acrylonitrile
2f. According to the literature8,12 this process a€ords a
benzopyrrocoline derivative, under PTC conditions in
benzene a complex mixture of products, while in acetonitrile
1-(2-substituted-ethyl)isoquinoline 4f, is formed, in good
yield.
The mechanistic pathway leading to the formation of 3
comprises a series of anionic reactions visualized in Scheme
2.2 A driving force is the regeneration of an aromatic system
in the last step.The products 4 are possibly formed either via
cleavage of 3 or directly from alkylated Reissert compounds;
both processes are promoted by base.
1-(2-Cyanoethyl)isoquinoline (4f ).ÐNitrile
1 (1.30 g, 5 mmol),
acetonitrile (8 cm3), TEBAC (0.057 g, 0.25 mmol), and 50% aqueous
NaOH (ca. 5 cm3) were stirred, then nitrile 2f (0.32 g, 6 mmol) was
added at 20±30 8C, and the mixture was stirred for 2 h (during
stirring ca. 10 cm3 of acetonitrile in three portions was added). The
mixture was worked-up according to procedure B, and the residue
was crystallized (EtOH) to give 4f, 0.59 g, 65% (Found: C, 78.79;
H, 5.37; N, 15.39. C12H10N2 requires C, 79.09; H, 5.53; N, 15.37%).
In conclusion, the presented work demonstrates the
usefulness of PTC for carbanionic reactions of Reissert
compound 1 with electrophilic alkenes 2.
Received, 22nd December 1997; Accepted, 26th January 1998
Paper E/7/09142G
Experimental
Melting points are uncorrected. Proton NMR spectra were
measured on a Varian Gemini 200 spectrometer in CDCl3. Column
chromatography was performed on Merck silica gel 60, eluent:
hexane±AcOEt (gradient). Reissert compound 1 was prepared by a
described procedure.13 All reactions were carried out under argon.
General Procedure for the Reaction of 1 with 2.ÐNitrile 1 (1.30 g,
5 mmol), benzene (7 cm3), TEBAC (0.057 g, 0.25 mmol) and alkene
2a±e,g,h (6 mmol) were stirred, then 50% aqueous NaOH (ca.
5 cm3) was added dropwise at 20±30 8C. The mixture was stirred for
the time indicated in Table 1, diluted with water, the phases were
separated, the water phase was extracted with benzene, the organic
phases were washed with water and worked-up according to pro-
cedure A or B. Procedure A. In the case of reactions 1±4 (Table 1)
the organic phases were dried (MgSO4), the solvent was evaporated
and the products were isolated by crystallization (3a±c, 4d) or
by column chromatography (4b,c). 1-(2-Benzoyl-2-methoxycarbonyl-
ethyl)isoquinoline (3a). (Found: C, 74.88; H, 5.30; N, 4.39.
References
1 M. Makosza, Tetrahedron Lett., 1969, 677.
2 A review on chemistry of Reissert compounds and their open-
chain analogs: J. V. Cooney, J. Heterocycl. Chem., 1983, 20,
823.
3 A. Jonczyk, Bull. Acad. Pol. Sci., Ser. Sci. Chim., 1974, 22, 849;
(Chem. Abstr., 1975, 82, 139936w).
4 E. V. Dehmlow and S. S. Dehmlow, Phase Transfer Catalysis,
Verlag Chemie, Weinheim, 3rd edn., 1993.
5 C. M. Starks, C. L. Liotta and M. Halpern, Phase-transfer
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6 M. Makosza and M. Fedorynski, Pol. J. Chem., 1996, 70, 1093.
7 M. Makosza and M. Fedorynski, in Handbook of Phase
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C
20H17NO3 requires C, 75.22; H, 5.36; N, 4.38%). 1-(2-Benzoyl-2-
isopropoxycarbonylethyl)isoquinoline (3b). (Found: C, 76.18; H, 5.97;
N, 3.95. 22H21NO3 requires C, 76.06; H, 6.09; N, 4.03%).
C
1-(2-Benzoyl-2-tert-butoxycarbonylethyl)isoquinoline (3c). (Found:
C, 76.54; H, 6.38; N, 3.80. C23H23NO3 requires C, 76.43; H, 6.41;
N, 3.87%). 1-(2-Iso-propoxycarbonylethyl)isoquinoline (4b). (Found:
C, 74.24; H, 6.75; N, 5.54. C15H17NO2 requires C, 74.05; H, 7.04;
N, 5.75%). 1-(2-tert-Butoxycarbonyl)isoquinoline (4c). (Found:
C, 74.76; H, 7.35; N, 5.42. C16H19NO2 requires C, 74.71; H, 7.39;
N, 5.45%). 1-(2-Methoxycarbonylpropyl)isoquinoline (4d). (Found:
C, 73.01; H, 6.59; N, 5.96. C14H15NO2 requires C, 73.34; H, 6.59;
N, 6.10%). Procedure B: in the case of reactions 5, 7 and 8 (Table 1)
the organic phases were extracted with 5% HCl, the combined
extracts were made more alkaline with Na2CO3, reextracted
13 M. Makosza, in Synteza Organiczna, PWN, Warszawa, 1972,
p. 299.