Regioselective synthesis of chromeno[4,3-c] isoquinolin-11-ones by radical cyclization

Article abstract of DOI:10.1081/SCC-200026621

A number of 4-tosyloxycoumarins were treated with N-methyl,N-(2- bromobenzyl)amine, and N-methyl,N-(2-bromo-5-methoxybenzyl)amine in refluxing ethanol to give different 4-[N-(2′-bromobenzyl),N-methyl] amino coumarins in 70-75% yield. These tertiary amine

Full text of DOI:10.1081/SCC-200026621

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Regioselective Synthesis
of Chromeno[4,3‐c]
isoquinolin‐11‐ones by Radical
Cyclization
K. C. Majumdar a & S. Sarkar a
a Department of Chemistry, University of Kalyani,
Kalyani, 741 235, West Bengal, India
Version of record first published: 06 Jan 2011.
To cite this article: K. C. Majumdar & S. Sarkar (2004): Regioselective Synthesis
of Chromeno[4,3‐c] isoquinolin‐11‐ones by Radical Cyclization, Synthetic
Communications: An International Journal for Rapid Communication of Synthetic
Organic Chemistry, 34:16, 2873-2883
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SYNTHETIC COMMUNICATIONSw
Vol. 34, No. 16, pp. 2873–2883, 2004
Regioselective Synthesis of Chromeno[4,3-c]
isoquinolin-11-ones by Radical Cyclization
*
K. C. Majumdar and S. Sarkar
Department of Chemistry, University of Kalyani, Kalyani,
West Bengal, India
ABSTRACT
A number of 4-tosyloxycoumarins were treated with N-methyl,N-(2-bro-
mobenzyl)amine, and N-methyl,N-(2-bromo-5-methoxybenzyl)amine in
refluxing ethanol to give different 4-[N-(20-bromobenzyl),N-methyl]
amino coumarins in 70–75% yield. These tertiary amine substrates
were then refluxed in dry benzene under nitrogen with tri-n-butyltin
chloride and sodium cyanoborohydride in the presence of 0.5–0.6 mol
equiv. of azobisisobutyronitrile(AIBN) for 4–5 hr to give the title com-
pounds in 65–68% yield.
Key Words: 2-Bromobenzyl bromide; AIBN; Sodium cyanoboro-
hydride; Tri-n-butyltin chloride; Radicals and radical reactions.
*
Correspondence: K. C. Majumdar, Department of Chemistry, University of Kalyani,
Kalyani 741 235, West Bengal, India; Fax: þ91-33-25828282; E-mail: kcm@klyuniv.
ernet.in.
2873
DOI: 10.1081/SCC-200026621
0039-7911 (Print); 1532-2432 (Online)
www.dekker.com
Copyright # 2004 by Marcel Dekker, Inc.

2874
Majumdar and Sarkar
INTRODUCTION
Aryl radical cyclization has recently emerged as a valuable tool for
organic synthesis.[1] In the course of our studies on the application of [3,3]-
sigmatropic rearrangements[2] for the synthesis of heterocyclic compounds,
we recently noted the unusual formation of [6,6]pyranopyrans in case of sub-
strates containing 3-hydroxycoumarin[3] and 5-hydroxy uracil[4] in the second
Claisen rearragement step. We became interested to investigate whether [6,6]
ring system could be achieved by tri-n-butyltin hydride mediated aryl radical
cyclization. The generation and subsequent reactions of aryl radical formed
from an aryl halides using tri-n-butyltin chloride, sodium cyanoborohydride,
and azobisisobutyronitrile (AIBN) is now well-established[5] and synthesis
of a wide range of natural products based on aryl radical cyclization have
been reported.[6] However, the literature reports on heteroaryl radicals are
relatively much less. Some examples by Snieckus[6a,b] and Harrowven[7]
involve pyridine and pyridyl radicals. Sundberg[8a] reported one example of
indonyl radical[8b,c] in the synthesis of iboga alkaloids. The cyclization of
radical derived from N-o-bromobenzylanilines to phenanthridine[9] was
very recently reported. Lack of significant work on the generation of radical
on heteroaromatic systems has prompted us to undertake a study on the
radical cyclization of 4-(20-bromobenzyl)amino[1]benzopyran-7-ones to
achieve the synthesis of [6,6]pyranoisoquinoline ring system.
RESULTS AND CONDITIONS
4-Tosyloxy[1]benzopyran-2-ones(1a–d) were synthesized following
published procedure. The compounds 1a–d were refluxed with N-(2-bromoben-
zyl),N-methylamine(2a), and N-(2-bromo-5-methoxybenzyl),N-methylamine(2b)
in ethanol for 8–10 hr to give 4[N-(20-bromobenzyl),N-methyl]amino[1]benzo-
pyran-7-ones(3a–h) in 70–75% yield (Sch. 1).
Compounds 3a–h were characterized from their elemental analyses and
spectroscopic data (vide Experimental). The substrate 3a was then refluxed in
dry benzene under nitrogen atmosphere with tri-n-butyltin chloride and
sodium cyanoborohydride in the presence of 0.5–0.6 mol equiv. of AIBN
for 4–5 hr to afford a cyclic product 4a, m.p. 1288C, yield 65%. Compound
4a was characterized from its elemental analysis and spectroscopic data.
The IR spectrum of the compound 4a showed nmax at 2950, 1710, 1580,
and 1390 cm21. The high field (300 MHz) 1H-NMR of the product 4a
exhibited a nine-proton singlet at d 1.38 for –C(CH3)3 protons, a three
proton singlet at d 3.15 for –NCH3 group, a two proton singlet at d 4.29
for –NCH2 group and rest are aromatic protons. The 13C-chemical shifts of

Synthesis of Chromeno[4,3-c]isoquinolin-11-ones
2875
Scheme 1.
compound 4a are assigned by DEPT experiment. Multiplicity are also esta-
blished by DEPT experiment. DEPT shows 12 protonated carbons among
which seven .CH–, four –CH3, and one –CH2–. 13C-NMR displayed the
following peaks: dc: 29.66 (–C(Me)3), 31.38 (–C(CH3)3), 41.66 (–NCH3),
54.51 (C-6), 107.89 (C-4a), 115.93 (C-1), 116.80 (C-9), 121.38 (C-8),
125.16 (C-7), 125.27 (C-10), 127.82 (C-4), 127.90 (C-10a), 128.93 (C-6a),
129.02 (C-4), 129.26 (C-4), 146.40 (C-11a), 151.33 (C-1a), 155.25 (C-11b),
160.46 (C-11). The mass spectrum of the product 4a showed a molecular
ion peak at m/z 319(Mþ). The generality of the reaction was tested by subject-
ing seven other substrates 3b–h under the same reaction condition to give
products 4b–h in 65–68% yield (Sch. 2).
The formation of products 4a–h from substrates 3a–h may be easily
explained by the generation of an aryl radical 5 in the tri-n-butyltin hydride
and AIBN mediated reaction.The aryl radical 5 may undergo cyclization by
Scheme 2.

2876
Majumdar and Sarkar
two different modes, a 6-endo trig cyclization[10] to afford the heterocyclic
radical 7 (“pathway a”) or a 5-exo trig cyclization to give the spiroheterocyclic
radical[11] 6 (not isolated, “pathway b”). The relatively more stable
heterocyclic radical 7 (benzyl radical) may form a conjugated double bond to
yield the products 4a–h by an unknown mechanism which is usual for this
type of synthetic sequence i.e. an oxidation step in a Bu3SnH mediated cycliza-
tions.[9b,12] The possibility for the formation of heterocyclic radical 7 via spiro-
cyclic radical 6 by a neophyl rearrangement[13] cannot be ruled out (Sch. 3).
It is known that radical cyclizations leading to six-membered rings are
usually less general than cyclization leading to five-membered rings. Six
membered ring forming reactions are also slower than five membered ring
forming reactions and are subject to competitive formation of reduced uncy-
clized by-products. However, appropriately substituted five hexenyl radicals
are known to undergo 6-endo cyclization to give six membered rings. It
is interesting to note that regioselectively six membered heterocyclic ring is
formed in all the cases studied at the present instance. The reaction
is mild, and regioselective. This is an attractive and simple methodology for
the synthesis of [6,6]pyrano isoquinoline ring system.
Scheme 3.

Synthesis of Chromeno[4,3-c]isoquinolin-11-ones
2877
EXPERIMENTAL
Melting points were determined in an open capillary and are uncorrected.
UV absorption spectra were recorded in EtOH on a Shimadzu UV-2401 PC
spectrophotometer (lmax in nm) and IR spectra in KBr discs on a Perkin
Elmer L 120-000A apparatus (nmax in cm21). 1H-NMR and 13C-NMR
spectra were run in CDCl3 with TMS as an internal standard on a Bruker
DPX-300 MHz and 75.5 MHz instrument at the Indian Institute of Chemical
Biology, Kolkata (chemical shifts in d ppm). Elemental analyses and mass
spectra were recorded by RSIC (CDRI), Lucknow on a JEOL D-300 (E1)
instrument. Silica gel (60–120 mesh) was obtained from Spectrochem,
India. Extracts were dried over anhydrous sodium sulfate. Petroleum ether
refers to the fraction boiling between 608C and 808C.
The starting materials (1a–d) for this study were prepared according to
our earlier published procedure.[14] The substrates 1a and 1c were newly
prepared from the 6-tertiarybutyl-4-hydroxycoumarin and 8-methyl-4-hydro-
xycoumarin for which characterization datas are given as follows.
6-Tertiarybutyl-4-tosyloxy[1]benzopyran-2-one (1a). M.p. 1778C;
yield 90%; UV(EtOH) lmax: 217, 274, 314 nm; IR(KBr) nmax: 1740, 1620,
1
1250 cm21; H-NMR (300 MHz): d 1.34 (s, 9H), 2.47 (s, 3H), 6.31 (s, 1H),
7.24–7.91 (m, 7H); Anal. calcd for C20H20O5S: C, 64.52; H, 5.37; found C,
64.66; H, 5.21 %.
8-Methyl-4-tosyloxy[1]benzopyran-2-one (1c). M.p. 1248C; yield
90%; UV(EtOH) lmax: 217, 275, 323 nm; IR(KBr) nmax: 1725, 1615,
1
1240 cm21; H-NMR (300 MHz): d 2.39 (s, 3H), 2.47 (s, 3H), 6.25 (s, 1H),
7.19–7.91 (m, 7H); Anal. calcd for C17H14O5S: C, 61.82; H, 4.24; found C,
61.95; H, 4.38 %.
General Procedure for the Preparation of 4-[N-Methyl-N-
(2-bromobenzyl)]aminobenzopyran-7-ones (3a–h)
4-Tosyloxy[1]benzopyran-2-ones (1a–d) (4 mmol) were refluxed with N-
methyl,N-(2-bromobenzyl)amine (2a) (4 mmol) or N-methyl,N-(2-bromo-5-
methoxybenzyl)amine (2b) (4 mmol) in alcohol (100 mL) for 8–10 hr. The
alcohol was removed under reduced pressure. The residual mass was extracted
with CHCl3 (3 ꢀ 50 mL) and the extract was washed with water (2 ꢀ 50 mL)
and dried (Na2SO4). The residual mass after removal of the solvent (CHCl3)
was subjected to column chromatography over silica gel using petroleum
ether–ethylacetate (2 : 1) as eluant to give compounds 3a–h which were
then recrystallized from chloroform–petroleum ether.

2878
Majumdar and Sarkar
4-[N-Methyl,N-(2-bromobenzyl)]amino-6-tertiarybutylbenzopyran-
7-one (3a). Yield 75%, white solid, m.p. 1388C; [Found C, 63.16; H, 5.41; N,
3.62%. C21H22NO2Br requires C, 63.01; H, 5.50; N, 3.50%]; nmax (KBr) 2980,
1705, 1620, 1405, 1360 cm21; lmax 218, 304 nm; dH (300 MHz, CDCl3) 1.35
(s, 9H, –C(CH3)3), 2.96 (s, 3H, –NCH3), 4.66 (s, 2H, –NCH2), 5.67 (s, 1H,
55CH), 6.92–6.94 (m, 1H, ArH), 7.24–7.32 (m, 2H, ArH), 7.38–7.44 (m, 1H,
ArH), 7.53–7.55 (m, 2H, ArH), 7.67–7.69 (m, 1H, ArH); m/z 399, 401 (Mþ).
4-[N-Methyl-N-(20-bromo-50-methoxybenzyl)]amino-6-tertiarybutyl-
benzopyran-7-one (3b). Yield 73%, white solid, m.p. 1228C; [Found C,
61.33; H, 5.47; N, 3.38%. C22H24NO3Br requires C, 61.41; H, 5.58; N,
3.26%]; nmax(KBr) 2950, 1705, 1610, 1405, 1350 cm21; lmax 215, 302 nm;
dH (300 MHz, CDCl3) 1.31 (s, 9H, –C(CH3)3), 2.81 (s, 3H, N–CH3), 3.80
(s, 3H, O–CH3), 4.53 (s, 2H, N–CH2), 5.62 (s, 1H, 55CH), 6.86–6.89
(m, 1H, ArH), 7.09–7.11 (m, 1H, ArH), 7.29–7.31 (m, 1H, ArH), 7.40–
7.43 (m, 1H, ArH), 7.56–7.59 (m, 1H, ArH), 7.69–7.70 (m, 1H, ArH).
4-[N-Methyl-N-(20-bromobenzyl)]amino-6-methylbenzopyran-7-one
(3c). Yield 70%, white solid, m.p. 1028C; [Found C, 60.26; H, 4.54; N,3.83%.
C18H16NO2Br requires C, 60.35; H, 4.47; N, 3.91%]; nmax (KBr) 2980, 1710,
1620, 1410, 1380 cm21; lmax 218, 305 nm; dH (300 MHz, CDCl3) 2.41 (s, 3H,
C–CH3), 2.99 (s, 3H, –NCH3), 4.67 (s, 2H, –NCH2), 5.66 (s, 1H, 55CH),
7.11–7.23 (m, 2H, ArH), 7.22–7.27 (m, 1H, ArH), 7.38–7.42 (m, 2H,
ArH), 7.45–7.47 (m, 1H, ArH), 7.67–7.69 (m, 1H, ArH).
4-[N-Methyl-N-(2-bromo-5-methoxybenzyl)]amino-6-methylbenzo-
pyran-7-one (3d). Yield 73%, white solid, m.p. 1188C; [Found C, 58.69; H,
4.78; N, 3.72%. C19H18NO3Br requires C, 58.78; H, 4.64; N, 3.61%]; nmax
(KBr) 2950, 1705, 1635, 1400, 1350 cm21; lmax 215, 302 nm; dH
(300 MHz, CDCl3) 2.46 (s, 3H, C–CH3), 2.96 (s, 3H, –NCH3), 3.79 (s, 3H,
O–CH3), 4.51 (s, 2H, –NCH2), 5.73 (s, 1H, 55CH), 6.77–6.81 (m, 2H,
ArH), 6.99–7.04 (m, 1H, ArH), 7.04–7.09 (m, 1H, ArH), 7.32–7.35
(m, 1H, ArH), 7.50–7.53 (m, 1H, ArH).
4-[N-Methyl-N-(2-bromobenzyl)]amino-8-methylbenzopyran-7-one
(3e). Yield 75%, white solid, m.p. 928C; [Found C, 60.26; H, 4.54; N,3.83%.
C18H16NO2Br requires C, 60.35; H, 4.47; N, 3.91%]; nmax (KBr) 2965, 1720,
1630, 1420, 1360 cm21; lmax 215, 305 nm; dH (300 MHz, CDCl3) 2.47 (s, 3H,
C–CH3), 2.97 (s, 3H, –NCH3), 4.61 (s, 2H, –NCH2), 5.67 (s, 1H, 55CH),
7.17–7.20 (t, J ¼ 7.6 Hz, 1H, ArH), 7.25–7.29 (m, 1H, ArH), 7.37–7.42
(m, 2H, ArH), 7.51–7.53 (d, J ¼ 7.6 Hz, 1H, ArH), 7.63–7.65
(d, J ¼ 7.9 Hz, 1H, ArH), 7.73–7.74 (d, J ¼ 7.9 Hz, 1H, ArH).
4-[N-Methyl-N-(2-bromo-5-methoxybenzyl)]amino-8-methylbenzo-
pyran-7-one (3f). Yield 73%, white solid, m.p. 1108C; [Found C, 58.65; H,
4.73; N, 3.79% C19H18NO3Br requires C, 58.78; H, 4.64; N, 3.61%];
n
max(KBr) 2960, 1700, 1620, 1430, 1350 cm21; lmax 216, 305 nm;

Synthesis of Chromeno[4,3-c]isoquinolin-11-ones
2879
dH (300 MHz, CDCl3) 2.49 (s, 3H, C–CH3), 2.91 (s, 3H, –NCH3), 3.81 (s, 3H,
O–CH3), 4.55 (s, 2H, –NCH2), 5.61 (s, 1H, 55CH), 6.80–6.83 (dd, J ¼ 2.90,
8.77 Hz, 1H, ArH), 7.06–7.07 (d, J ¼ 2.90 Hz, 1H, ArH), 7.17–7.20
(t, J ¼ 7.6 Hz, 1H, ArH), 7.42–7.44 (d, J ¼ 7.1 Hz, 1H, ArH), 7.51–7.53
(d, J ¼ 8.77 Hz, 1H, ArH), 7.73–7.75 (d, J ¼ 7.1 Hz, 1H, ArH).
4-[N-Methyl-N-(2-bromobenzyl)]aminobenzopyran-7-one (3g). Yield
70%, white solid, m.p. 1128C; [Found C, 59.47; H, 4.14; N, 3.95%.
C17H14NO2Br requires C, 59.32; H, 4.07; N,4.07%]; nmax (KBr) 2943, 1697,
1603, 1438,1353 cm21; lmax 216, 302 nm; dH (300MHz, CDCl3) 2.97 (s, 3H,
–NCH3), 4.59 (s, 2H, NCH2), 5.72 (s, 1H, 55CH), 7.09–7.14 (m, 1H, ArH),
7.22–7.27 (m, 2H, ArH), 7.34–7.53 (m, 4H, ArH), 7.63–7.65 (m, 1H, ArH).
4-[N-Methyl-N-(2-bromo-5-methoxybenzyl)]aminobenzopyran-7-one
(3h). Yield 72%, white solid, m.p. 1308C; [Found C, 57.63; H, 4.28; N,
3.83%. C18H16NO3Br requires C, 57.77; H, 4.28; N, 3.74%]; nmax (KBr)
2950, 1700, 1620, 1430, 1360 cm21; lmax 215, 300 nm; dH (300 MHz,
CDCl3) 2.93 (s, 3H, N–CH3), 3.80 (s, 3H, O–CH3), 4.51 (s, 2H, –NCH2),
5.73 (s, 1H, 55CH), 6.80–6.85 (m, 1H, ArH), 7.05–7.12 (m, 1H, ArH),
7.25–7.33 (m, 2H, ArH), 7.52–7.59 (m, 2H, ArH), 7.74–7.76 (m, 1H, ArH).
General Procedure for the Preparation of (4a–h)
A suspension of the compounds 3a–h (0.5 mmol), nBu3SnCl (0.075 mL),
Na(CN)BH3 (1 mmol) and AIBN (0.5–0.6 mol equiv.) in 7 mL of dry benzene
were refluxed for 4–5 hr under N2 atmosphere. Solvent was evaporated under
reduced pressure and the residue was taken in 10 mL of water and was
extracted with CHCl3 (3 ꢀ 10 mL). The combined organic extract was
washed with 1% aqueous NH4OH (2 ꢀ 10 mL) and brine, and dried
(Na2SO4). Evaporation of the solvent furnished the residual mass which
was then magnetically stirred with saturated solution of potassium fluoride
(5 mL) for 24 hr. It was then extracted with CHCl3 (3 ꢀ 10 mL) and was
washed with water for several times and dried (Na2SO4). The residual
mass after removal of the solvent (CHCl3), was subjected to column
chromatography using petroleum ether–ethyl acetate (3 : 1) as eluant to
give cyclized products 4a–h which were then recrystallized from chloro-
form–petroleum ether.
3-Tertiarybutyl-5-methylchromeno[4,3-c]isoquinolin-11-one (4a). Yield
65%, solid, m.p. 1288C; [Found C, 78.81; H, 6.63; N, 4.23%. C21H21NO2 requires
C, 78.99; H, 6.58; N, 4.39%]; nmax (KBr) 2950, 1710, 1580, 1390 cm21; lmax 218,
263 nm; dH (300 MHz, CDCl3) 1.38 (s, 9H, C(CH3)3), 3.15 (s, 3H, –NCH3), 4.29
(s, 2H, –NCH2), 7.15–7.17 (s, 1H, ArH), 7.28–7.40 (m, 4H, ArH), 7.53–7.57
(m, 1H, ArH), 8.01–8.04 (m, 1H, ArH); 13C-NMR(75.5 MHz, CDCl3) dc:

2880
Majumdar and Sarkar
29.66 (–C(Me)3), 31.38 (–C(CH3)3), 41.66 (–NCH3), 54.51 (C-6), 107.89
(C-4a), 115.93 (C-1), 116.80 (C-9), 121.38 (C-8), 125.16 (C-7), 125.27
(C-10), 127.82 (C-4), 127.90 (C-10a), 128.93 (C-6a), 129.02 (C-4), 129.26
(C-3), 146.40 (C-11a), 151.33 (C-1a), 155.25 (C-11b), 160.46 (C-11); m/z
319 (Mþ).
3-Tertiarybutyl-8-methoxy-5-methylchromeno[4,3-c]isoquinolin-11-
one (4b). Yield 67%, solid, m.p. 1278C; [Found C, 75.45; H, 6.71; N,
4.16%. C22H23NO3 requires C, 75.64; H, 6.59; N, 4.01%]; nmax (KBr)
2930, 1720, 1570, 1390 cm21; lmax 218, 263 nm; dH (300 MHz, CDCl3)
1.35 (s, 9H, C(CH3)3), 3.09 (s, 3H, –NCH3), 3.75 (s, 3H, –OCH3), 4.21
(s, 2H, –NCH2), 6.92–6.94 (m, 1H, ArH), 7.04–7.05 (m, 1H, ArH), 7.13–
7.14 (m, 2H, ArH), 7.22–7.23 (m, 1H, ArH), 7.87–7.91 (m, 1H, ArH); m/z
349 (Mþ).
3,5-Dimethylchromeno[4,3-c]isoquinolin-11-one (4c). Yield 70%
white solid, m.p. 1658C; [Found C, 77.82; H, 5.33; N, 5.12%.
C18H15NO2 requires C, 77.98; H, 5.41; N, 5.05%]; nmax (KBr) 2905,
1705, 1570, 1380 cm21; lmax 218, 290 nm; dH(300 MHz, CDCl3) 2.44
(s, 3H, C–CH3), 3.16 (s, 3H, –NCH3), 4.29 (s, 2H, –NCH2), 7.30–7.33
(m, 4H, ArH), 7.37–7.59 (m, 2H, ArH), 8.05–8.08 (m, 1H, ArH); m/z
277 (Mþ).
8-Methoxy-3,5-dimethylchromeno[4,3-c]isoquinolin-11-one (4d). Yield
67 %, solid, m.p. 1048C; [Found C, 74.36; H, 5.42; N, 4.63%. C19H17NO3
requires C, 74.27; H, 5.53; N, 4.56%]; nmax (KBr) 2956, 1699, 1541,
1369 cm21; lmax 224, 245 nm; dH (300 MHz, CDCl3) 2.48 (s, 3H, C–CH3),
3.14 (s, 3H, –NCH3), 3.84 (s, 3H, O–CH3), 4.27 (s, 2H, –NCH2), 6.87–6.90
(dd, J ¼ 2.50, 8.40 Hz, 1H, ArH), 7.09–7.12 (d, J ¼ 2.50 Hz, 1H, ArH), 7.19–
7.22 (d, J ¼ 8.40 Hz, 1H, ArH), 7.28–7.38 (m, 2H, ArH), 7.87–7.89 (m, 1H,
ArH); m/z 307 (Mþ).
1,5-Dimethylchromeno[4,3-c]isoquinolin-11-one (4e). Yield 66%,
solid, m.p. 1088C; [Found C, 77.82; H, 5.33; N, 5.12%. C18H15NO2 requires
C, 77.98; H, 5.41; N, 5.05%]; nmax (KBr) 2925, 1720, 1596, 1380 cm21; lmax
216, 259 nm; dH (300 MHz, CDCl3) 2.42 (s, 3H, C–CH3), 3.14 (s, 3H,
–NCH3), 4.21 (s, 2H, –NCH2), 7.29–7.32 (m, 2H, ArH), 7.37–7.40
(m, 2H, ArH), 7.44–7.49 (m, 1H, ArH), 7.57–7.59 (m, 1H, ArH), 8.04–
8.06 (m, 1H, ArH); m/z 277 (Mþ).
8-Methoxy-1,5-dimethylchromeno[4,3-c]isoquinolin-11-one (4f). Yield
69%, solid, m.p. 1228C; [Found C, 74.36; H, 5.42; N, 4.63%. C19H17NO3
requires C, 74.27; H, 5.53; N, 4.56%]; nmax (KBr) 2900, 1720, 1590,
1370cm21; lmax 218, 265 nm; dH (300MHz, CDCl3) 2.45 (s, 3H, C–CH3),
3.01 (s, 3H, –NCH3), 3.81 (s, 3H, –OCH3), 4.20 (s, 2H, –NCH2), 6.91–
6.94 (m, 1H, ArH), 7.20–7.22 (m, 2H, ArH), 7.36–7.43 (m, 2H, ArH),
7.91–7.93 (m, 1H, ArH); m/z 307 (Mþ).

Synthesis of Chromeno[4,3-c]isoquinolin-11-ones
2881
5-Methylchromeno[4,3-c]isoquinolin-11-one (4g). Yield 68%, solid,
m.p. 1178C; [Found C, 77.51; H, 5.01; N, 5.25%. C17H13NO2 requires C,
77.57; H, 4.94; N, 5.32%]; nmax (KBr) 2920, 1719, 1565, 1393 cm21; lmax
217, 264 nm; dH (300 MHz, CDCl3) 3.17 (s, 3H, –NCH3), 4.30 (s, 2H,
–NCH2), 7.14–7.16 (m, 2H, ArH), 7.27–7.41 (m, 3H, ArH), 7.48–7.53
(m, 2H, ArH), 8.02–8.04 (m, 1H, ArH); m/z 263 (Mþ).
8-Methoxy-5-methylchromeno[4,3-c]isoquinolin-11-one (4h). Yield
65%, solid, m.p. 1328C; [Found C, 73.64; H, 5.16; N, 4.94%. C18H15NO3
requires C, 73.72; H, 5.12; N, 4.78%], nmax (KBr) 2900, 1720, 1580,
1400 cm21; lmax 217, 264 nm; dH (300 MHz, CDCl3) 3.08 (s, 3H, –NCH3)
3.92 (s, 3H, –OCH3), 4.23 (s, 2H, –NCH2), 6.90–6.94 (dd, J ¼ 2.50,
8.40 Hz, 1H, ArH), 7.13–7.14 (d, J ¼ 2.50 Hz, 1H, ArH), 7.20–7.23
(d, J ¼ 8.40 Hz, 1H, ArH), 7.31–7.36 (m, 1H, ArH), 7.39–7.42 (m, 1H,
ArH), 7.53–7.59 (m, 1H, ArH), 7.93–7.94 (m, 1H, ArH); m/z 293 (Mþ).
ACKNOWLEDGMENT
We thank the CSIR (New Delhi) for financial assistance. One of us (S.S.)
is thankful to CSIR (New Delhi) for a Senior Research Fellowship.
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Received in India April 12, 2004