A synthesis of n-formylenamides of isoquinoline

Article abstract of DOI:10.3987/COM-05-10645

N-Formylenamides of isoquinoline (6) were obtained from N-[2-(2-acyl-4,5-dimethoxyphenyl)ethyl]formamides (5) by cyclization in the presence of catalytic amount of p-toluensulfonic acid. The starting keto formamides (5) were obtained by acylation of a N-[

Full text of DOI:10.3987/COM-05-10645

HETEROCYCLES, Vol. 68, No. 2, 2006
387
HETEROCYCLES, Vol. 68, No. 2, 2006, pp. 387 - 393. © The Japan Institute of Heterocyclic Chemistry
Received, 5th December, 2005, Accepted, 12th January, 2006, Published online, 17th January, 2006. COM-05-10645
A SYNTHESIS OF N-FORMYLENAMIDES OF ISOQUINOLINE
Iliyan Ivanov,* Stoyanka Nikolova, Stela Statkova-Abeghe, and Plamen
Angelov
University of Plovdiv, Department of Organic Chemistry, 4000 Plovdiv, Bulgaria
E-mail: ivanov@argon.acad.bg
Abstract – N-Formylenamides of isoquinoline (6) were obtained from N-[2-(2-
acyl-4,5-dimethoxyphenyl)ethyl]formamides (5) by cyclization in the presence of
catalytic amount of p-toluensulfonic acid. The starting keto formamides (5) were
obtained by acylation of a N-[2-(3,4-dimethoxyphenyl)ethyl]formamides (1) with
carboxylic acids or their anhydrides in polyphosphoric acid (PPA).
INTRODUCTION
The enamides have proven to be versatile reagents in the contemporary organic synthesis.1-6 Enamide
derivatives of isoquinoline, in particular, have been utilized as starting compounds in numerous
asymmetric,7,8 cycloaddition9-11 and photochemical reactions for synthesis of isoquinoline alkaloids or
their analogs.12-15 Some enamides of this type, like polycarpine, have also been isolated as natural
products.3 The enamides of isoquinoline are usually synthesized by acylation of 3,4-dihydroisoquinolines
with acid chlorides or anhydrides.1,2 A few years ago we demonstrated a different approach, in which N-
[2-(2-acyl-4,5-dimethoxyphenyl)ethyl]amides were obtained by acylation of N-acyl-3,4-
dimethoxyphenylethyl-amines with carboxylic acids in PPA and then cyclized in acidic media to provide
various enamides of isoquinoline.16 The success of this approach depends to an extent on the reaction
conditions and on the nature of the N-acyl group in the starting compounds, since a cleavage of this group
in the course of the reaction would lead to the formation 3,4-dihydroisoquinolines instead of enamides as
end products. In this paper we report an extention of this method, allowing the synthesis of N-formyl-
enamides of isoquinoline, which represent interest as intermediates in the synthesis of protoberberines,
aporphines, dibenzopyrrocolines.12-15 Until now these compounds have been synthesized only by
acylation of 3,4-dihydroisoquinolines with formic, formic-acetic or formic-pivalic anhydrides1,2,7-10 which
are not commercially available.

388
HETEROCYCLES, Vol. 68, No. 2, 2006
N
N
N
Protoberberine
Aporphine
Dibenzopyrrocoline
RESULTS AND DISCUSSION
Our initial studies showed that the reaction of N-[2-(3,4-dimethoxyphenyl)ethyl]formamides (1)17 and
carboxylic acids in PPA for 2 h at 80oC leads to a mixture of N-[2-(2-acyl-4,5-dimethoxyphenyl)-
ethyl]formamides (5a-g) and 3,4-dihydroisoquinolines (7a-g). Later we found that the ratio of 5 to 7
could be increased when the reaction was carried out at lower temperature (50oC), using the more reactive
acid chlorides or anhydrides as acylating agents (Table 1).
MeO
R
MeO
R
MeO
R
PPA
Δ
+
NH_CHO
NH_CHO
N
MeO
MeO
MeO
1
5
O
7
+
CH2
R1
R1CH2COOH (2)
R1
or
(R1CH2CO)2O (3);
R1CH2COCl (4)
PTS
C2H4Cl2
MeO
MeO
R
PPA
Δ
N_CHO
6
R1
Scheme 1
Table 1
7
Yield [%]
Compound
R
R1
5
6
a
b
c
d
e
f
H
H
H
H
H
H
60
53
59
61
60
55
57
80
82
65
71
85
62
70
13
18
17
10
13
19
11
CH3
CH2CH3
CH(CH3)2
C6H5
CH3
CH3
H
C6H5
g

HETEROCYCLES, Vol. 68, No. 2, 2006
389
Practically, however, it is more convenient to be used carboxylic acids in this reaction instead of their
anhydrides or chlorides. The reaction in this case depended on the order of mixing the reagents. Thus, two
equivalents of the carboxylic acid should be mixed with excess of PPA and heated at 50oC for 30 min
prior to addition of one equivalent of the formamide (1). The increase of 5 to 7 ratio under these
conditions could be attributed to an initial formation of anhydride in situ from the carboxylic acid. When
the reaction was carried out at higher temperatures (80∼100oC), the 3,4-dihydroisoquinolines 7 are the
predominant product.
We assume that under the reaction conditions enamides (6) are initially obtained from 5 and subsequent
cleavage of the formyl group in 6 furnishes the 3,4-dihydroisoquinolines (7). In support of this
assumption, we found that the reaction of formamide (1) with benzoic acid under the same conditions
stoped at the first stage 3,4-dihydroisoquinoline, (Scheme 2) caused by to give no possibility for enamide
formation in this case.
MeO
MeO
MeO
PPA
Δ
PPA
Δ
NH_CHO
NH_CHO
N
MeO
MeO
MeO
1
5h
O
7
+
C6H5
C6H5
C6H5COOH
Scheme 2
Furthermore, the cyclization of 5a-g could be stopped at the enamide stage when milder acidic conditions
are applied. Their cyclization in less acidic medium as in the presence of catalytic amount of p-
toluenesulfonic acid monohydrate (PTS) afforded the corresponding enamides (5a-g) to (6a-g) for 30 min
in refluxing 1,2-dichloroethane solution. When the isolated in this way enamides (6) were treated with
PPA at 80-100oC, the N-formyl group is cleaved and 3,4-dihydroisoquinolines (7) were obtained, which
are known compounds.10,16,18
EXPERIMENTAL
Melting points were determined on a Boëtius hotstage apparatus and are uncorrected. Infrared spectra
were recorded on a FT-IR Perkin-Elmer 1750. 1H-NMR and 13C-NMR spectra were recorded on a Bruker
250 MHz device by using CDCl3 as solvent. Chemical shifts (δ, ppm) were referenced to the chemical
shifts of either TMS as an internal standard and coupling constants are indicated in Hz. Unless otherwise
noted, all the NMR spectra were taken at room temperature (ca. 295 K). MS spectra were recorded on a
JEOL JMS-D300 spectrometer (70 eV). All new compounds had correct parent ion peaks by mass
spectrometry. All experiments were monitored by TLC using DC Alufolien Kieselgel 60.
Polyphosphoric acid was obtained from 85% phosphoric acid and P2O5 (1:1 w/w).
Synthesis of N- [2-(2-acyl-4,5-dimethoxyphenyl)ethyl)]formamides (5a-h); Typical procedure:

390
HETEROCYCLES, Vol. 68, No. 2, 2006
N-[2-(3,4-dimethoxyphenyl)ethyl]formamides (3 mmol) and the corresponding anhydride (6 mmol) were
dissolved in CH2Cl2 (5-10 mL) in an open flask and polyphosphoric acid (10 g) was added. (When
carboxylic acid was used instead of anhydride then the carboxylic acid was initially mixed with the
polyphosphoric acid and the mixture was heated for 30 min at 50oC. To this mixture then was added N-
[2-(3,4-dimethoxyphenyl)ethyl]formamide). The reaction mixture was stirred carefully at 50ºC for 2 h,
then poured on crushed ice and extracted with CH2Cl2 (3 х 20 mL). The organic phase was dried over
Na2SO4, filtered on a short column with neutral Al2O3. The products, after evaporation of the solvent,
were recrystallized from 2:1hexane-ethyl acetate.
N-[2-(2-Acetyl-4,5-dimethoxyphenyl)ethyl]formamide (5a): mp 90-92°C. IR (KBr): 3335, 1678, 1655.
1H-NMR: 2.60 (s, 3H), 3.03 (t, 2H, J=6.6 Hz), 3.58 (q, 2H, J=5.5 Hz), 3.92 (s, 3H), 3.93 (s, 3H), 6.68 (s,
1H, br, NH), 6.77 (s, 1H), 7.28 (s, 1H), 8.10 (s, 1H, CHO). 13C-NMR: 29.23, 32.51, 40.04, 55.88, 55.89,
112.79, 113.96, 129.63, 133.98, 146.74, 151.92, 161.33 (NH-CHO), 200.75 (CO). Anal. Calcd for
C13H17NO4: C 62.14, H 6.82, N 5.57. Found: C 62.12, H 6.98, N 5.64.
N-[2-(4,5-Dimethoxy-2-propionylphenyl)ethyl]formamide (5b): mp 101-103°C. IR (KBr): 3321, 1674,
1656. 1H-NMR: 1.16 (t, 3H, J=7.2 Hz), 2.93 (t, 2H, J=6.5 Hz), 2.92 (q, 2H, J=7.2 Hz), 3.53 (q, 2H, J=5.3
13
Hz), 3.87 (s, 3H), 3.88 (s, 3H), 6.74 (s, 1H), 6.99 (s, 1H, br, NH), 7.13 (s, 1H), 8.06 (s, 1H, CHO). C-
NMR: 8.40, 32.26, 34.26, 40.27, 55.90, 56.03, 111.73, 113.82, 129.96, 133.42, 146.84, 151.69, 161.49
(NH-CHO), 204.24 (CO). Anal. Calcd for C14H19NO4: C 63.38, H 7.22, N 5.28. Found: C 63.02, H 6.96,
N 5.02.
N-[2-(2-Butyryl-4,5-dimethoxyphenyl)ethyl]formamide (5c): mp 93.5-95°C. IR (KBr): 3325, 1675,
1
1657. H-NMR: 0.96 (t, 3H, J=7.5 Hz), 1.70 (sextet, 2H, J=7.4 Hz), 2.85 (t, 2H, J=7.3 Hz), 2.92 (t, 2H,
J=6.8 Hz), 3.53 (q, 2H, J=6.4 Hz), 3.88 (s, 3H), 3.89 (s, 3H), 6.74 (s, 1H), 7.04 (s, 1H, br, NH), 7.11 (s,
13
1H), 8.07 (s, 1H, CHO). C-NMR: 13.72, 17.90, 32.13, 40.35, 43.07, 55.92, 56.07, 111.74, 113.79,
130.30, 133.37, 146.85, 151.70, 161.51 (NH-CHO), 204.06 (CO). Anal. Calcd for C15H21NO4: C 64.50, H
7.58, N 5.01. Found: C 64.21, H 7.45, N 4.96.
N-{2-[4,5-Dimethoxy-2-(3-methylbutyryl)phenyl]ethyl}formamide (5d): mp 79-82°C. IR (KBr): 3319,
1
1672, 1654. H-NMR: 0.95 (d, 6H, J=6.6 Hz), 2.17-2.24 (m, 1H), 2.74 (d, 2H, J=6.9 Hz), 2.92 (t, 2H,
J=6.8 Hz), 3.55 (q, 2H, J=5.2 Hz), 3.88 (s, 3H), 3.89 (s, 3H), 6.74 (s, 1H), 7.03 (s, 1H, br, NH), 7.63 (s,
13
1H), 8.07 (s, 1H, CHO). C-NMR: 22.59, 25.37, 32.01, 40.37, 50.17, 55.91, 56.08, 111.78, 113.76,
130.67, 133.34, 146.83, 151.70, 161.49(NH-CHO), 204.03(CO). Anal. Calcd for C16H23NO4: C 65.51, H
7.90, N 4.77. Found: C 65.21, H 7.85, N 4.74.
N-[2-(4,5-Dimethoxy-2-phenylacetylphenyl)ethyl]formamide (5e): mp 103-104°C. IR (KBr): 3324,
1
1672, 1648. H-NMR: 2.91(t, 2H, J=6.7 Hz), 3.49 (q, 2H, J=5.5 Hz), 3.87 (s, 3H), 3.89 (s, 3H), 4.20 (s,
13
2H), 6.74 (s, 1H), 6.77 (s, 1H, br, NH), 7.24 (s, 1H), 7.17-7.35 (m, 5H), 8.03 (s, 1H, CHO). C-NMR:

HETEROCYCLES, Vol. 68, No. 2, 2006
391
28.66, 38.50, 48.26, 55.83, 56.04, 111.44, 113.31, 127.19, 128.64, 128.85, 129.28, 133.77, 146.72, 152.90,
162.67 (NH-CHO), 200.07 (CO). Anal. Calcd for C19H21NO4: C 69.71, H 6.47, N 4.28. Found: C 69.97,
H 6.53, N 4.52.
N-[2-(2-Acetyl-4,5-dimethoxyphenyl)-1-methylethyl]formamide (5f): mp 124-125°C. IR (KBr): 3320,
1
1673, 1646. H-NMR: 1.33 (d, 3H, J=6.4 Hz), 2.61 (s, 3H), 2.73 (dd, 1H, J=4.3, 14.3 Hz), 3.08 (dd, 1H,
J=11.1, 14.3 Hz), 3.91 (s, 3H), 3.92 (s, 3H), 4.15-4.25 (m, 1H), 6.77 (s, 1H), 7.15 (s, 1H), 7.31 (s, 1H, br
13
NH), 7.94 (s, 1H, CHO). C-NMR: 21.59, 29.44, 38.60, 47.40, 55.87, 56.05, 112.38, 113.79, 130.18,
133.56, 146.78, 152.02, 160.77 (NH-CHO), 202.3(CO). Anal. Calcd for C14H19NO4: C 63.38, H 7.22, N
5.28. Found: C 63.49, H 7.54, N 5.32.
N-{2-[4,5-Dimethoxy-2-(2-oxo-2-phenylethyl)phenyl]-1-methylethyl}formamide (5g): mp 122-123°C.
1
IR (KBr): 3318, 1673, 1642. H-NMR: 1.28 (d, 3H, J=6.4 Hz), 2.66 (dd, 1H, J=4.3, 11.3 Hz), 2.95 (dd,
1H, J=11.2, 2.2 Hz), 3.88 (s,3H), 3.90 (s, 3H), 4.14-4.30 (m, 1H), 4.20 (s, 2H), 6.76 (s, 1H), 7.19 (s, 1H,
br, NH), 7.21 (s, 1H), 7.22-7.35 (m, 5H), 7.90 (s, 1H, CHO). 13C-NMR: 21.6, 38.5, 47.4, 48.4, 55.9, 56.1,
111.8, 113.7, 127.1, 128.7, 129.3, 129.9, 133.8, 146.8, 152.0, 160.8 (NH-CHO), 201.8(CO). Anal. Calcd
for C20H23NO4: C 70.36, H 6.79, N 4.10. Found: C 70.44, H 6.53, N 4.25.
N-[2-(2-Benzoyl-4,5-dimethoxyphenyl)ethyl]formamide (5h): mp 73-75°C from ether. IR (KBr): 3322,
1
1659, 1648. H-NMR: 2.83 (t, 2H, J=8 Hz), 3.40-3.65 (m, 2H), 3.75 (s, 3H), 3.95 (s, 3H), 6.85 (s, 1H),
6.91 (s, 1H), 7.20 (s, 1H, br, NH), 7.45-7.95 (m, 5H), 8.18 (s, 1H, CHO). Anal. Calcd for C18H19NO4: C
68.99, H 6.11, N 4.47. Found: C 68.74, H 6.23, N 4.23.
Synthesis of 1-alkylidene-, 1-phenylmethylidene-3,4-dihydro-1H-isoquinoline-2-carbaldehyde (6a-
g); Typical procedure: Solution of N-[2-(2-acyl-4,5-dimethoxyphenyl)ethyl)]formamides (3 mmol) and
a catalytic amount of p-toluenesulfonic acid (20 mg) in 20 mL of 1,2-dichloroethane was refluxed for 30
min. The solvent was removed under reduced pressure and the remainder was taken with CH2Cl2 and
washed with 5% aq. Na2CO3. The organic phase was dried over Na2SO4. The products, after evaporation
of the solvent, were purified by column chromatography on neutral Al2O3 with ether as eluent.
6,7-Dimethoxy-1-methylene-3,4-dihydro-1H-isoquinoline-2-carbaldehyde (6а): mp 135-137°C (lit.,8
mp 136.5-138°C). IR (KBr): 1662, 1622. 1H-NMR: 2.75 (t, 2H, J=6 Hz), 3.85 (s, 3H), 3.87 (s, 3H), 3.90
(t, 2H, J=6 Hz), 4.78 (d, 1H, J=2 Hz, C=CH2), 5.13 (d, 1H, J=2 Hz, C=CH2), 6.58 (s, 1H), 7.03 (s, 1H),
8.53 (s, 1H, CHO). 13C-NMR: 28.68, 38.59, 55.78, 55.93, 94.60, 106.50, 110.95, 121.84, 127.27, 140.67,
147.88, 149.90, 160.41 (CHO). Anal. Calcd for C13H15NO3: C 66.94, H 6.48, N 6.00. Found: C 66.89, H
6.41, N 6.03.
1-Ethylidene-6,7-dimethoxy-3,4-dihydro-1H-isoquinoline-2-carbaldehyde (6b): mp 117-118°C. IR
1
(KBr): 1661, 1620. H-NMR (CDCl3): 1.89 (d, 3H, J=7.1 Hz), 2.84 (t, 2H, J=6.1 Hz), 3.86 (t, 2H, J=6.1
Hz), 3.87 (s, 3H), 3.90 (s, 3H), 6.02 (q, 1H, J=7.1 Hz, C=CH-CH3), 6.58 (s, 1H), 7.03 (s, 1H), 8.21 (s, 1H,

392
HETEROCYCLES, Vol. 68, No. 2, 2006
13
CHO). C-NMR: 13.43, 28.41, 38.88, 55.77, 55.91, 105.60, 111.99, 111.34, 123.94, 126.18, 134.52,
147.78, 149.09, 162.07 (CHO). Anal. Calcd for C14H17NO3: C 68.00, H 6.93, N 5.66. Found: C 67.92, H
6.74, N 5.53.
6,7-Dimethoxy-1-propylidene-3,4-dihydro-1H-isoquinoline-2-carbaldehyde (6c): mp 110-112°C. IR
(KBr): 1663, 1618. 1H-NMR: 1.11 (t, 3H, J=7.5 Hz), 2.29 (pentet, 2H, J=7.4 Hz), 2.84 (t, 2H, J=6.2 Hz),
3.89 (t, 2H, J=6.2 Hz), 3.87 (s, 3H), 3.92 (s, 3H), 5.88 (t, 1H, J=7.4 Hz, C=CH-CH2-CH3), 6.58 (s, 1H),
13
7.30 (s, 1H), 8.22 (s, 1H, CHO). C-NMR: 14.59, 21.07, 28.38, 38.99, 55.76, 55.94, 105.66, 111.34,
118.68, 123.89, 126.34, 133.03, 147.77, 149.11, 161.91 (CHO). Anal. Calcd for C15H19NO3: C 68.94, H
7.33, N 5.36. Found: C 68.88, H 7.44, N 5.30.
1-Isobutylidene-6,7-dimethoxy-3,4-dihydro-1H-isoquinoline-2-carbaldehyde (6d): mp 153-154°C. IR
(KBr): 1661, 1616. 1H-NMR: 1.10 (d, 6H, J=6.5 Hz), 2.65-2.77 (m, 1H), 2.85 (t, 2H, J=6.1 Hz), 3.87 (s,
3H), 3.90 (t, 2H, J=6.1 Hz), 3.93 (s, 3H), 5.71 (d, 1H, J=10.3 Hz, C=CH-), 6.57 (s, 1H), 7.02 (s, 1H), 8.24
13
(s, 1H). C-NMR: 23.5, 26.8, 28.4, 39.2, 55.8, 56.0, 105.7, 111.4, 124.1, 125.1, 126.5, 131.6, 147.8,
149.2, 161.9 (CHO). Anal. Calcd for C16H21NO3: C 69.79, H 7.69, N 5.09. Found: C 69.70, H 7.72, N
5.14.
1-Benzylidene-6,7-dimethoxy-3,4-dihydro-1H-isoquinoline-2-carbaldehyde (6e): mp 151-152°C. IR
1
(KBr): 1666, 1635. H-NMR: 2.89 (t, 2H, J=6.1 Hz), 3.89 (s, 3H), 3.95 (s, 3H), 3.99 (t, 2H, J=6.1 Hz),
13
6.61 (s, 1H, C=CH-Ph), 6.81 (s, 1H), 7.22 (s, 1H), 7.19-7.40 (m, 5H), 8.12 (s, 1H, CHO). C-NMR:
28.72, 38.53, 55.86, 56.09, 105.75, 111.52, 113.31, 123.28, 126.98, 127.69, 128.68, 128.88, 133.85,
135.24, 147.98, 149.78, 162.66. Anal. Calcd for C19H19NO3: C 73.77, H 6.19, N 4.53. Found: C 73.57, H
6.08, N 4.48.
6,7-Dimethoxy-3-methyl-1-methylene-3,4-dihydro-1H-isoquinoline-2-carbaldehyde (6f): mp 98-99°C.
1
IR (KBr): 1664, 1620. H-NMR: 1.17 (d, 3H, J=6.8 Hz), 2.59 (dd, 1H, J=15.3, 1.9 Hz), 3.23 (dd, 1H,
J=15.3, 5.9 Hz), 3.98 (s, 3H), 4.00 (s, 3H), 4.94 (d, 1H, J=2 Hz, C=CH2), 5.15 (m, 1H), 5.39 (d, 1H, J=2
Hz, C=CH2), 6.69 (s, 1H), 7.25 (s, 1H), 8.71 (s, 1H, CHO). 13C-NMR: 17.22, 34.70, 42.66, 55.83, 56.10,
94.22, 112.24, 114.99, 122.70, 125.51, 135.24, 144.8, 147.85, 162.49. Anal. Calcd for C14H17NO3: C
68.00, H 6.93, N 5.66; Found: C 68.20, H 6.87, N 5.70.
1-Benzylidene-6,7-dimethoxy-3-methyl-3,4-dihydro-1H-isoquinoline-2-carbaldehyde (6g): mp 42-
44°C IR (KBr): 1660, 1618. 1H-NMR: 1.37 (d, 3H, J=6.9 Hz), 2.66 (dd, 1H, J=16.2, 1.2 Hz), 3.33 (dd, 1H,
J=16.2, 6.1 Hz), 3.89 (s, 3H), 3.99 (s, 3H), 5.10-5.20 (m, 1H), 6.59 (s, 1H, C=CH-), 6.91 (s, 1H), 7.16-
13
7.45 (m, 6H), 8.09 (s, 1H, CHO). C-NMR: 17.23, 34.73, 42.70, 55.86, 56.12, 105.53, 112.21, 114.97,
127.10, 128.58, 128.92, 131.91, 135.24, 147.87, 150.03, 162.59 (CHO). Anal. Calcd for C20H21NO3: C
74.28, H 6.55, N 4.33. Found: C 74.30, H 6.50, N 4.30.

HETEROCYCLES, Vol. 68, No. 2, 2006
393
All of the obtained 3,4-dihydroisoquinoline derivatives (7) were characterized by their mp, IR and NMR
spectra and compared with the data known from the literature.10,16,18
ACKNOWLEDGEMENTS
We acknowledge financial support from the Fund for scientific research of the University of Plovdiv.
REFERENCES
1. G. R. Lenz, Synthesis, 1978, 489.
2. A. L. Campbell and G. R. Lenz, Synthesis, 1987, 421.
3. G. R. Lenz and C. M. Woo, J. Heterocycl. Chem., 1981, 18, 691.
4. G. R. Lenz, Heterocycles, 1987, 26, 721.
5. G. R. Lenz, R. A. Lessor, P. W. Rafalko, and Z. Kosarych, J. Chem. Soc., Perkin Trans. I, 1993, 745.
6. G. R. Lenz, R. A. Lessor, P. W. Rafalko, E. Ezell, and Z. Kosarych, Helv. Chim. Acta, 2004, 87, 690.
7. M. Kitamura, M. Tsukamoto, H. Takaya, and R. Noyori, Bull. Chem. Soc. Jpn., 1996, 69, 1695.
8. M. Kitamura, Y. Hsiao, M. Ohta, M. Tsukamoto, T. Ohta, H. Takaya, and R. Noyori, J. Org. Chem.,
1994, 59, 297.
9. N. Atanes, S. Perez, E. Guitian, L. Castedo, and J. M. Saa, Tetrahedron, 1994, 50, 11257.
10. N. Atanes, E. Guitian, C. Saa, L. Castedo, and J. M. Saa, Tetrahedron Lett., 1987, 28, 817.
11. N. Atanes, L. Castedo, E. Guitian, and J. M. Saa, Heterocycles, 1987, 26, 1183.
12. K. W. Bentley, ‘The Isoquinoline Alkaloids’, Vol. 1, ed. by B. Ravindranath, Harwood Academic
Publishers, 1998.
13. V. Deulofeu, J. Comin, and M. J. Vernengo, ‘The Alkaloids’, Vol. 10, ed. by R. H. F. Manske,
Academic Press, New York, 1968.
14. M. Shamma, ‘The Isoquinoline Alkaloids, Chemistry and Pharmacology’, Academic Press, New
York, 1972.
15. T. Kametani, ‘The Total Synthesis of Natural Products’, Vol. 3, ed. by J. ApSimon, Wiley & Sons,
New York, 1977.
16. A. Venkov and I. Ivanov, Tetrahedron, 1996, 52, 12299.
17. A. Venkov and I. Ivanov, Synth. Comm., 1993, 23, 1707.
18. (a) K. Orito, T. Matsuzaki, H. Suginome, and R. Rodrigo, Heterocycles, 1988, 27, 2403. (b) T. Fujii,
M. Ohba, O. Yonemitsu, and Y. Ban, Chem. Pharm. Bull., 1982, 30, 598. (c) G. Tsastsas, Ann.
Pharm. Franc., 1952, 10, 61 (Chem. Abstr., 1952, 46, 11208). (d) S. Rastogi, V. Kansal, and A.
Bhaduri, Ind. J. Chem., 1983, 22B, 234. (e) M. Ragab, A. Mohsen, M. Omar, and A. Hazzaa,
Pharmazie, 1974, 29, 178.