Reaction of 3-substituted and 4-bromo-3-substituted isoquinolin-1-(2H)-ones with propargyl bromide

Article abstract of DOI:10.1002/jhet.5570380307

Isoquinolinones were brominated using N-bromosuccinimide in dimethylformamide at room temperature to give 4-bromo-3-substituted isoquinolin-1-(2H)-ones. The reaction of these isoquinolinones with propargyl bromide in the presence of anhydrous potassium carbonate yielded N and O-alkylated products.

Full text of DOI:10.1002/jhet.5570380307

May-Jun 2001
Reaction of 3-Substituted and 4-Bromo-3-Substituted Isoquinolin-1-
(2H)-ones with Propargyl Bromide
597
Cyril Odianose Usifoh
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Benin, Benin City, Nigeria
Received July 27, 2000
Isoquinolinones were brominated using N-bromosuccinimide in dimethylformamide at room temper-
ature to give 4-bromo-3-substituted isoquinolin-1-(2H)-ones. The reaction of these isoquinolinones with
propargyl bromide in the presence of anhydrous potassium carbonate yielded N and O-alkylated products.
J. Heterocyclic Chem., 38, 597 (2001).
In continuation of the search for interesting heterocyclic
bromide with the isoquinolinone 6a gave both N- and
O-alkylated products 7a and 8a, while the isoquinolinone 6b
gave only O-alkylated product 8b when the substitution at
carbon 3 is an isopropyl group.
The O-alkylation products were obtained when there is
steric hindrance or a bulky group at position 3. Bromination
at position 4 probably contributed to the steric hindrance
such that O-alkylation is favored. It is worth mentioning that
the phenyl group, though bulky, may also act by stabilizing
the isoquinolinone through its aromatic system, which is
absent in the isopropyl group.
compounds with the N-prop-2-ynyl moiety, which may have
possible biological activity, the isoquinolinones 3 and 6 were
synthesized according to literature procedures [1,2,3]. The
reactions and formation of heterocycles from processes
involving propargyl bromides have continued to receive
attention in recent times [4,5,6].
Bromination of the isoquinolinones 3a and 3b at position 4
was found to proceed smoothly and optimally in dimethyl-
formamide with N-bromosuccinimide at room temperature
within 2 hours. The proton nmr clearly shows a singlet at δ
6.67 and δ 6.32 ppm for 3a and 3b, respectively corre-
sponding to position 4, and the absence of a singlet in the
isoquinolinones 6a and 6b. The reaction of propargyl
The nmr spectra show that the prop-2-ynyl moiety of the
O-alkylated products are shifted downfield compared with
that of the N-alkylated products. The methylene doublet
signal appears at about δ 5.10 ppm for O-alkylated products
compared to δ 4.20 ppm for the N-alkylated products while
the triplet of the acetylene proton is situated at about δ
2.40-2.50 ppm for O-alkylated and between δ 2.10 and δ
2.30 ppm for N-alkylated products. In addition, the infra-red
13
and C-nmr spectra confirmed the absence of the carbonyl
functional group in O-alkylated products, which is present in
the N-alkylated products. The syntheses of 4a and 5a have
been previously reported with the only characterization being
melting points and elemental analyses [7]. An improved
synthetic method and relevant spectroscopic data are
presented in this work. All compounds were characterized
spectroscopically with support from elemental analyses.
EXPERIMENTAL
Melting points were determined with a Kofler hot stage
microscope and are uncorrected. The reactions and purity of the
products were monitored by tlc using pre-coated silica gel plates
(Merck 60F ). Silica gel Merck 60 (70-230 mesh) was used
254
1
13
for column chromatography. The H and C nmr spectra were
recorded on a Varian Gemini 200 with tetramethylsilane as
internal standard, infra red spectra were measured on a Perkin-
Elmer type 457 and the mass spectra were determined using
Varian MAT 44S, EI: 70 eV.
General Synthetic Procedure for Isoquinolines 3a-b.
N-Methyl-o-toluamide (2).
To o-toluic acid 1 (10.2 g, 0.075 mol) in a 250 ml flask was
added thionyl chloride (15.0 g, 0.125 mol) and refluxed for 2

Vol. 38
C. O. Usifoh
598
hours. After the excess thionyl chloride was distilled off, 60 ml
of diethyl ether was added and the mixture gradually poured into
30 ml of a stirring ice-cooled solution of 40% methylamine. The
precipitate formed was filtered and the mother liquor was
concentrated in vacuo to afford some more of the precipitate.
Crystallization of the precipitate from ethanol-water gave 8.5 g
(76%) of 2 as a crystalline solid; mp 76-77 °C (Lit. [1] 78-79
room temperature for 2 hours and then poured into cold water
(50 ml). The filtration of the solid formed and subsequent crys-
tallization from ethanol afforded needles of 6a or 6b.
4-Bromo-3-phenyl-isoquinolin-1-(2H)-one (6a).
This compound was prepared according to the general proce-
dure to give 6a as colorless needles, 1.22 g (90%) mp 270-208
°C; ir (potassium bromide): v 3300 (NH), 3005, 2990 (C- H),
1
°C); H nmr (deuterochloroform): δ 2.37 (s, 3H, CH ), 2.88-2.90
3
-1
1
1640, 1600, 1590, 1140, 780, 700 cm ; H nmr (dimethyl-
(d, J = 4.8 Hz, 3H, NCH ), 6.14 (br, 1H, NH), 7.10-7.17 (m, 2H,
3
13
sulphoxide-d ): δ 7.49 (m, 5H, Ar-H), 7.61-7.68 (t, J = 7.9 Hz,
Ar-H), 7.23-7.28 (m, 2H, Ar-H); C nmr (deuterochloroform):
6
1H, 6-H), 7.84-7.88 (t, J = 7.9 Hz, 1H, 7-H), 7.93 (d, J = 8.0 Hz,
δ 20.3, 27.1, 126.2, 127.2, 130.3, 131.5, 136.5, 137.0, 171.5; ms:
13
m/z: 149 [M+. ].
1H, 5-H), 8.28 (d, J = 8.0 Hz, 1H, 8-H), 11.81 (br, 1H, NH);
C
nmr (dimethylsulphoxide-d ): δ 97.8 (C-4), 125.5, 126.0, 127.2,
6
Synthesis of 3-Phenyl-isoquinolin-1-(2H)-one 3a and
3-Isopropyl-isoquinolin-1-(2H)-one 3b.
127.4, 128.2, 129.4, 129.6, 133.6, 134.8, 136.2, 140.4, 161.1
(C = 0); ms m/z 301 (100%) [M+. +1], 299 (99) [M+. -1], 255
(12), 220 (69), 193 (80), 177 (5), 165 (78), 150 (4), 114 (6), 96
To N-methyl-o-toluamide 2 (7.46 g, 50 mmol) in 300 ml of
dry tetrahydrofuran under nitrogen in a 500 ml flask cooled in
an ice-salt bath, was added slowly n-butyllithium (80 ml, 135
mmol) such that the internal temperature never exceeded 15 °C.
The resulting orange-red reaction mixture was stirred at 0 °C for
1.5 hours, cooled to -63 °C and benzonitrile or isobutyronitrile
(62 mmol) in 40 ml tetrahydrofuran were added via a syringe as
quickly as possible. The cooling bath was removed and the reac-
tion mixture allowed to warm up to room temperature. Saturated
ammonium chloride solution (150 ml) was carefully added to
reaction mixture until the resulting phases separated. The
organic phase was washed with water (2 x 30 ml), brine (2 x 30
ml) and dried over anhydrous sodium sulphate. Subsequent
filtration and removal of organic solvent in vacuo gave a crude
product, which was crystallized from ethanol or ethanol-water.
(7), C
H NOBr (300.155).
15 10
Anal. Calcd. for C
H NOBr: C, 60.02; H, 3.35; N, 4.67.
15 10
Found: C, 60.00; H, 3.30; N, 4.60.
4-Bromo-3-isopropyl-isoquinolin-1-(2H)-one (6b).
This compound was prepared according to the general proce-
dure to give 6b as colorless needles, 1.20 g (80 %) mp: 184-185
°C; ir (potassium bromide): v 3300 (NH), 3000, 2995 (C-H),
-1
1
1645, 1600, 1590, 1140, 780, 700 cm ; H nmr (deuterochloro-
form): δ 1.40-1.43 (d, J = 7.2 Hz, 6H, 2 x CH ), 3.66-3.80 (sept,
3
J = 7.2 Hz, 1H, -CH(CH ) ), 7.47-7.55 (ddd, J = 1.2, 6.9, 8.1
3 2
Hz, 1H, 7-H), 7.72-7.79 (ddd, J = 1.2, 7.0, 8.2 Hz, 1H, 6-H),
7.96-8.00 (dd, J = 1.2, 8.0 Hz, 1H, 5-H), 8.40-8.44 (dd, J = 1.3,
13
8.0 Hz, 1H, 8-H), 10.82 (br, 1H, N-H); C nmr (deuterochloro-
form): δ 20.1 (2 x CH ), 32.4, 98.9, 125.2, 126.5, 126.8, 127.6,
3
3-Phenyl-isoquinolin-1-(2H)-one (3a).
133.5, 137.3, 144.5, 163.4; ms: m/z 267 (99%) [M+. +1], 266
(18) [M+.], 265 (100) [M+. -1], 250 (73), 237 (56), 223 (5), 186
(34) [M+. –Br], 171 (81), 153 (28), 142 (20), 128 (16), 115 (47),
This product was obtained by the condensation-hydrolysis-
cyclization of dilithiated 2 with benzonitrile. Crystallization
from ethanol afforded 3a as needles; 2.1 g (91%), mp 199-200
°C (Lit. [2] 198-199 °C); ir (potassium bromide): v 3320 (NH),
89 (14), 63 (6); C
H NOBr (266.138).
12 12
Anal. Calcd. for C
H NOBr: C, 54.19; H, 4.55; N, 5.26.
12 12
-1
1
Found: C, 53.98; H, 4.42; N, 5.06.
3000, 2990 (C-H), 1650, 1600, 1140, 770, 700 cm ; H nmr
(deuterochloroform): δ 6.77 (s, 1H, 4-H), 7.24-7.48 (m, 4H,
Ar-H), 7.49 (d, J = 7.8 Hz, 1H, Ar-H), 7.52-7.54 (t, J = 7.8 Hz,
1H, Ar-H), 7.73-7.78 (m, 2H, Ar-H), 8.38 (d, J = 8.0 Hz, 1H,
General Reaction Procedure of Isoquinolinones 3a-b and 6a-b
with Propargyl Bromide.
To isoquinolinone (3.03 mmol) either 3a, 3b, 6a or 6b and
potassium carbonate (3.03 mmol) in a 100 ml two-necked flask
was added dimethylformamide (30 ml). The solution was stirred
at room temperature for 15 minutes. Propargyl bromide 0.12 g
(3.03 mmol) was added slowly and the reaction mixture carefully
monitored by tlc till the total disappearance of isoquinolinone.
The reaction mixture was poured into water (60 ml) and extracted
into ethyl acetate (3 x 30 ml). The combined organic phase was
washed with brine (2 x 20 ml), dried over anhydrous sodium
sulphate and the organic solvent removed in vacuo to give a crude
product, which was crystallized or subjected to column
chromatography for purification and isolation of the product.
13
Ar-H), 11.60 (br, 1H, NH); C nmr (deuterochloroform): δ
104.2, 124.9, 126.2, 126.5, 126.6, 127.4, 129.1, 129.5, 132.8,
134.3, 138.3, 139.6, 164.0; ms: m/z 222 (18%) [M+.].
3-Isopropyl-isoquinolin-1-(2H)-one (3b).
This product was crystallized from ethanol-water and gave 3b
as fine needles; 0.99 g (40%) mp 188-189 °C (Lit [2]; 188-189
°C); ir (potassium bromide): v 3325 (NH), 3000, 2990, 1648,
1
1608, 1556, 1476, 1384, 840, 754 cm-1; H nmr (dimethyl-
sulphoxide-d ): δ 1.21 (d, J = 6.8 Hz, 6H, 2 x CH3), 2.76 (sept,
6
J = 6.8 Hz, 1H, CH(CH ) ), 6.32 (s, 1H, 4-H), 7.37 (t, J = 8.0
3 2
Hz, 1H, Ar-H), 7.55 (d, J = 8.0 Hz, 1H, Ar-H), 7.61 (t, J = 8.0
Hz, 1H, Ar-H), 8.12 (d, J = 8.0 Hz, 1H, Ar-H), 10.82 (br, 1H,
Isolation of 3-Phenyl-2-(prop-2-ynyl)-isoquinolin-1-(2H)-one 4a
and 3-Phenyl-1-(prop-2-ynyloxy)-isoquinoline 5a.
13
NH); C nmr (dimethylsulphoxide-d ): δ 21.3, 31.0 (2 x CH ),
6
3
99.5, 124.4, 125.9, 126.5, 132.3, 138.3, 148.2, 162.6; ms: m/z
188 (16%) [M+.], 187 (10) [M+. -1], 172 (67), 159 (20).
The reaction of 3a with propargyl bromide according to the
general procedure yielded a crude product after 72 hours. This
was purified by column chromatography (hexane:dichloro-
methane 1:1 to dichloromethane). 3-Phenyl-1-(prop-2-ynyloxy)-
isoquinoline 5a was isolated first, followed by 3-phenyl-2-(prop-
2-ynyl)-isoquinolin-1-(2H)-one 4a. 4a and 5a were crystallized
Bromination of Isoquinolinones (3a-b).
A sample of N-bromosuccinimide (4.5 mmol) was added to a
stirred solution of isoquinolinone 3a or 3b (4.5 mmol) in
dimethylformamide (20 ml). The reaction mixture was stirred at

May-Jun 2001
Reaction of 3-Substituted and 4-Bromo-3-Substituted Isoquinolin-1-(2H)-ones
599
from hexane-dichloromethane to give colorless needles of 4a
and 5a.
3-Isopropyl-1-(prop-2-ynyloxy)-isoquinoline (5b).
This compound was prepared according to the general proce-
dure to give 5b as colorless oil, 0.21 g (30%), oil; (sodium chlo-
ride): v 3110, 2985, 1620, 1600, 1590, 1140, 770, 700 cm ; H
3-Phenyl-2-(prop-2-ynyl)-isoquinolin-1-(2H)-one (4a).
-1
1
This compound was prepared according to the general
procedure to give 4a as colorless needles, 0.18 g (23%) mp:
132-133 °C; (Lit [7] 132-133 °C); ir (potassium bromide): v
nmr (deuterochloroform): δ 1.29-1.31 (d, J = 7.1 Hz, 6H, 2 x
CH ), 2.42 (s, 1H, ≡CH), 2.95-3.01 (sept, J = 7.2 Hz, 1H,
3
-CH(CH ) ), 5.15 (s, 2H, CH ), 7.00 (s, 1H, 4-H), 7.39 (t,
3 2
2
-1
1
2990, 2970, 1660, 1620, 1240, 1150, 780, 700 cm ; H nmr
J = 8.0 Hz, 1H, Ar-H), 7.53 (t, J = 7.9 Hz, 1H, Ar-H), 7.61 (d,
J = 7.9 Hz, 1H, Ar-H), 7.61 (d, J = 7.9 Hz, 1H, Ar-H), 8.17 (d,
(deuterochloroform): δ 2.22 (t, J = 2.0 Hz, 1H, ≡CH), 4.58
(d, J = 2.0 Hz, 2H, -CH -), 6.41 (s, 1H, 4-H), 7.43 (m, 5H,
2
13
J = 8.0 Hz, 1H, Ar-H); C nmr (deuterochloroform): δ 22.3,
Ar-H), 7.51 (m, 2H, Ar-H), 7.59 (m, 1H, Ar-H), 8.43 (d,
35.6, 53.4, 73.8, 79.7, 110.4, 117.9, 123.9, 125.7, 125.9, 130.3,
13
J = 8.0 Hz, 1H, Ar-H); C nmr (deuterochloroform): δ 35.7
+.
+.
138.9, 157.6, 158.3; ms: m/z 225 (26%) [M ], 224 (30) [M
1], 210 (100), 195 (27), 182 (22), 167 (21), 154 (10), 141 (5),
128 (8), 115 (10), 89 (7); C NO (225.291).
-
(CH ), 71.5 (≡CH), 79.3 (C≡), 107.9, 124.7, 125.8, 126.6,
2
127.9, 128.5, 129.1, 132.5, 135.2, 136.2, 142.9, 162.3; ms:
H
15 15
+.
+.
m/z 259 (61%) [M +1], 258 (100) [M ], 232 (16), 202 (12),
190 (6), 176 (10), 165 (15), 152 (4), 129 (6), 115 (7), 89 (11);
Anal. Calcd. for C
H NO: C, 79.97; H, 6.71; N, 6.22.
15 15
Found: C, 79.94; H, 6.68; N, 6.12.
C
H NO (259.308).
18 13
Isolation of 4-Bromo-3-phenyl-2-(prop-2-ynyl)-isoquinolin-1-
(2H)-one 7a and 4-Bromo-3-phenyl-1-(prop-2-ynyloxy)-
isoquinoline 8a.
Anal. Calcd. for C
H NO: C, 83.38; H, 5.05; N, 5.40.
18 13
Found: C, 83.18; H, 5.00; N, 5.30.
3-Phenyl-1-(prop-2-ynyloxy)-isoquinoline (5a).
The reaction of 6a with propargyl bromide according to the
general procedure yielded a crude product after 10 hours which
on column chromatography (hexane to hexane:dichloromethane
1:1) gave 8a and then followed by 7a. Crystallization from
hexane-dichloromethane mixture afforded colorless needles of
8a and 7a.
This compound was prepared according to the general
procedure to give 5a as colorless needles, 0.54 g (68 %), mp:
92-93 °C; (Lit [7] 87-88 °C); ir (potassium bromide): v 3000,
-1
1
2980, 1620, 1600, 1540, 320, 780, 700 cm ; H nmr (deutero-
chloroform): δ 2.53 (t, J = 2.4 Hz, 1H, ≡CH ), 5.31 (d, J = 2.2
Hz, 2H, -CH -), 7.40 (t, J = 8.0 Hz, 1H, Ar-H), 7.70 (s, 1H,
2
4-Bromo-3-phenyl-2-(prop-2-ynyl)-isoquinolin-1-(2H)-one (7a).
4-H), 7.76 (d, J = 8.0 Hz, 1H, Ar-H), 8.16 (m, 2H, Ar-H), 8.38
13
(d, J = 8.0 Hz, 1H, Ar-H); C nmr (deuterochloroform): δ
This compound was prepared according to the general proce-
dure to give 7a as colorless needles, 0.17 g (15%); mp: 163-164
°C; ir (potassium bromide): v 3210, 2100, 1640 (C=0), 1600,
53.6 (-CH ), 74.2 (≡CH), 79.5 (C≡), 111.0, 118.5, 124.1,
2
126.5, 126.6, 128.4, 128.6, 130.7, 138.9, 139.0, 147.4, 158.5;
+.
+.
+.
-1
1
ms: m/z 260 (4) [M +1], 259 (25) [M ], 258 (100) [M -1],
229 (8), 202 (6), 190 (4), 165 (11), 129 (7), 115 (3), 89 (11);
1560, 760, 700 cm . H nmr (deuterochloroform): δ 2.20 (t,
J = 2.5 Hz, 1H, 3'-H), 4.55 (d, J = 2.5 Hz, 2H, 1'-H), 7.42-7.51
(m, 2H, Ar-H), 7.53-7.64 (m, 4H, Ar-H), 7.72-7.84 (ddd,
J = 1.4, 7.8, 8.0 Hz, 1H, Ar-H), 7.98-8.02 (dd, J = 1.3, 7.8 Hz,
C
H NBrO (259.308).
18 13
Anal. Calcd. for C
H NBrO: C, 83.38; H, 5.05; N, 5.40.
18 13
13
Found: C, 83.32; H, 5.15; N, 5.38.
1H, Ar-H), 8.52-8.58 (dd, J = 1.3, 7.9 Hz, 1H, Ar-H); C nmr
(deuterochloroform): δ 36.9, 71.7, 78.9, 102.9, 123.9, 125.5,
Isolation of 3-Isopropyl-2-(prop-2-ynyl)-isoquinolin-1-(2H)-one
4b and 3-Isopropyl-1-(prop-2-ynyloxy)-isoquinoline 5b.
126.7, 128.5, 128.9, 129.6, 129.7, 133.4, 133.6, 135.5, 135.6,
+.
+.
141.5, 161.4; ms: m/z 340 (15%) [M +2], 339 (18) [M +1],
The reaction of 3b with propargyl bromide according to the
general procedure yielded a crude product after 48 hours. This
was purified by column chromatography (hexane to hexane-
dichloromethane 1:1) to give 5b as an oil and then closely
followed by 4b which was recrystallised from hexane-
dichloromethane.
+.
338 (100) [M ], 337 (85), 336 (88), 310 (11), 292 (13), 257 (55)
[M -Br], 219 (22), 202 (22), 190 (24), 176 (9), 114 (4), 88 (8),
+.
C
H NBrO (338.204).
18 12
Anal. Calcd. for C
H NBrO: C, 63.93; H, 3.58; N, 4.14.
18 12
Found: C, 64.00; H, 3.60; N, 4.20.
4-Bromo-3-phenyl-1-(prop-2-ynyloxy)-isoquinoline (8a).
3-Isopropyl-2-(prop-2-ynyl)-isoquinolin-1-(2H)-one (4b).
This compound was prepared according to the general proce-
dure to give 8a as colorless needles, 0.9 g (80 %); mp: 79-81 °C;
ir (potassium bromide): v 3300, 2900, 2885, 2100, 1600, 1560,
This compound was prepared according to the general proce-
dure to give 4b as colorless needles, 0.41 g (60 %), mp: 116-117
°C; ir (potassium bromide): v 3000, 2995 (C-H), 1670, 1610,
-1
1
1400, 770, 700 cm ; H nmr (deuterochloroform): δ 2.52 (t,
J = 2.5 Hz, 1H, 3'-H), 5.20 (d, J = 2.5 Hz, 2H, 1'-H), 7.42-7.54
(m, 3H, Ar-H), 7.58-7.68 (ddd, J = 1.1, 7.3, 8.1 Hz, 1H, Ar-H),
7.76-7.86 (m, 3H, Ar-H), 8.24-8.38 (t, J = 8.0 Hz, 2H, Ar-H);
-1
1
1595, 1540, 1240, 1140, 780, 700 cm ; H nmr (deuterochloro-
form): δ 1.24-1.26 (br, 6H, 2 x CH ), 2.14 (s, 1H, ≡CH),
3
3.13-3.16 (m, 1H, CH(CH ) ), 4.89 (s, 2H, -CH -), 6.33 (s, 1H,
3 2
2
13
4-H), 7.23-7.35 (m, 2H, Ar-H), 7.48 (t, J = 8.0 Hz, 1H, Ar-H),
C nmr (deuterochloroform): δ 54.2 (CH ), 74.6 (C-3'), 79.2
2
13
8.27 (d, 1H, J = 8.0 Hz, Ar-H); C nmr (deuterochloroform): δ
(C-2'), 110.7, 119.7, 124.4, 127.5, 127.8, 128.3, 130.2, 131.7,
132.0, 137.8, 140.6, 158.8; ms: m/z 340 (3) [M +2], 339 (20%)
[M +1], 338 (100) [M ], 337 (22), 336 (96), 310 (3), 292 (26),
257 (32) [M -Br], 229 (9), 219 (13), 190 (14), 169 (6), 111 (5),
+.
22.9 (2 x CH ) 29.7, 32.1, 71.6, 79.2, 102.6, 124.2, 125.5, 126.1,
3
+.
+.
128.0, 132.4, 136.7, 148.7, 162.8 (C=0); ms: m/z 226 (8%)
+.
+.
+.
[M + 1], 225 (36) [M ], 210 (100), 195 (27), 182 (17), 167 (18),
154 (6), 128 (15), 115 (18), 89 (11), 77 (4); C H NO (225.291).
85 (9), 57 (13); C
H NBrO (338.204).
15 15
18 12
Anal. Calcd. for C
H NO: C, 79.97; H, 6.71; N, 6.22.
Anal. Calcd. for C
H NBrO: C, 63.93; H, 3.58; N, 4.14.
18 12
15 15
Found: C, 97.96; H, 6.70; N, 6.19.
Found: C, 63.74; H, 3.52; N, 4.02.

Vol. 38
C. O. Usifoh
600
4-Bromo-3-isopropyl-1-(prop-2-ynyloxy)-isoquinoline (8b).
Acknowledgement.
I thank Dr. G. Bergenthal, Department of Pharmaceutical
Chemistry, University of Münster, Germany for running nmr and
mass spectra.
The reaction of 6b with propargyl bromide according to the
general procedure yielded a crude product after 12 hours.
Subsequent purification of the crude product using column
chromatography (hexane) gave colorless oil of 8b; 0.80 g
(90%); ir: (sodium chloride): v = 3205, 2100, 1600, 1520,
REFERENCES AND NOTES
-1
1
760, 700 cm ; H nmr (deuterochloroform): δ 1.33-1.37 (d,
J = 6.7 Hz, 6H, 2 x CH ), 2.51 (t, J = 2.4 Hz, 1H, 3'-H),
[1] R. L. Vaulx, W. H. Puterbaugh and C. R. Hauser, J. Org.
Chem., 29, 3514 (1964).
[2] G. S Poindexter, J. Org. Chem., 47, 3787 (1982).
[3] A. A. Patchett, S. E. De Laszlo and W. J. Greenlee,
Substituted 1-(2H)-Isoquinolinones. European Patent Application, 502
0575 (1992).
[4] H. Liu, S. B. Ko, H. Josien and D. P. Curran, Tetrahedron.
Lett., 36, 8917 (1995).
[5] J. Reisch, A. R. R. Rao and C. O. Usifoh, Monatsh. Chem.,
125, 79 (1994).
3
3.70-3.84 (sept, J = 6.7 Hz, 1H, -CH(CH ) ) 5.20 (d, J = 2.4
3 2
Hz, 2H, 1'-H), 7.48-7.57 (ddd, J = 1.2, 7.0, 8.2 Hz, 1H, 7-H),
7.68-7.77 (ddd, J = 1.2, 7.1, 8.4 Hz, 1H, 6-H), 8.14 (d, J = 8.6
13
Hz, 1H, 5-H). 8.21-8.25 (d, J = 8.2 Hz, 1H, 8-H); C nmr
(deuterochloroform): δ 21.5, 29.8, 34.2, 53.7, 74.2, 79.4,
110.2, 119.3, 124.2, 126.6, 131.5, 137.4, 154.8, 157.7; ms:
+.
+.
m/z 305 (25%) [M +1], 304 (61) [M ], 303 (25), 302 (57),
288 (32), 275 (6), 224 (5), 209 (100), 88 (5), 184 (3), 170
[6] J. Reisch, A. R. R. Rao and C. O. Usifoh, Monatsh. Chem.,
124, 1217 (1993).
[7] C. Bogentoft, L. Kronberg and B. Danielsson, Acta. Pharm.
Suecica., 6, 489 (1969).
(12), 115 (11); C
H NBrO (304.187).
15 14
Anal. Calcd. for C
H NBrO: C, 59.23; H, 4.64; N, 4.61.
15 14
Found: C, 59.10; H, 4.40; N, 4.52.