W. M. Abdou, A. F. M. Fahmy, A. A. Kamel
FULL PAPER
(m, 13 H, Ph-H); δC (CDCl3) ϭ 21.9 (Ph-CH3), 39.8 (3-CϪH), O, acetyl]; NMR: δH (CDCl3) ϭ 2.36 (s, 3 H, PhϪCH3), 2.43 [s, 3
174.3 (4-CϭO), 195.2 (CϭO, benzoyl); m/z (EI) (%): 339 [Mϩ]
(100), 311 (33), 262 (12), 234 (25). Compound 7c is partially soluble
H, C(O)CH3], 3.66 (s, 1 H, 3-C-H), 6.85Ϫ7.78 (m, 13 H, Ph-H);
m/z (EI) (%): 277 [Mϩ] (100), 249 (34), 144 (58). Compound 7d is
in 10% aq. NaOH, and gives no colour reaction with 1% alcoholic partially soluble in 10% NaOH aq., and gives no colour reaction
FeCl3 solution.
with 1% alcoholic FeCl3 solution.
The second fraction (7:3, v/v) was triturated with a small volume
of cyclohexane to give yellow crystals of (2-benzoylmethylenetri-
phenylphosphorane) o-(4-methylphenyl)benzophenone oxime (9a)
(570 mg, 22%), m.p. 193Ϫ195 °C (benzene) [C41H32NO3P (617.69):
calcd. C 79.72, H 5.22, N 2.27, P 5.01; found C 79.64, H 5.15, N
2.13, P 5.07%]; IR (KBr): ν˜ ϭ 3419 (NOH), 1750 [C-7Ϫ(O)], 1682
[C-9Ϫ(O)], 1610 (CϭN), 1478 (CϭP), 976 (PϪPh) cmϪ1; NMR:
δH (CDCl3) ϭ 2.41 (s, 3 H, PhϪCH3), 7.24Ϫ8.46 (m, 28 H, Ph-H),
8.78 (s, 1 H, NOH); δC (CDCl3) ϭ 22.2 (Ph-CH3), 87.6 (d, JC,Pϭ
96.8 Hz, CϪP), 154.5 (CϭNOH), 192.8 (CϭO, benzoyl), 196.3 (7-
CϭO); δP ([D6]DMSO) ϭ 15.98; m/z (EI) (%): 617 [Mϩ] (20), 589
(8), 511 (29), 478 (26), 301 (100).
2-Acetyl-3-methyl-5-(4-methylphenyl)benzocyclohepten-1-one (14):
This compound was obtained (hexane/EtOAc, 4:6, v/v) as colour-
less crystals (280 mg, 22%), m.p. 175Ϫ177 °C (MeCN). [C21H18O2
(302.37): calcd. C 83.42, H 6.00; found C 83.32, H 5.87%]; IR
(KBr): ν˜ ϭ 1725 (1-CϭO), 1656 cmϪ1 (CϭO, acetyl); NMR: δH
(CDCl3) ϭ 2.18, 2.47 (2s, 2 ϫ 3 H, 3-CϪCH3 and PhϪCH3), 2.55
[s, 3 H, C(O)CH3], 6.67 (s, 1 H, 4-C-H), 7.46Ϫ8.23 (m, 8 H, Ph-
H); δC (CDCl3)
ϭ 13.8 (3-C-CH3), 21.8 (Ph-CH3), 28.65
[C(O)CH3), 111.4 (2-C), 144.6 (4-C), 163.5 (1-CϭO), 206.7 (CϭO,
acetyl); m/z (EI) (%): [Mϩ], 302 (18), 274 (25), 259 (55), 231 (100),
216 (12), 201 (31).
2,3-Diacetyl-4-(4-methylphenyl)-α-naphthol (13): This compound
was obtained (hexane/EtOAc, 2:8 v/v) as colourless crystals
(440 mg, 33%), m.p. 185Ϫ187 °C (C2H5OH). [C21H18O3 (318.37):
calcd. C 79.22, H 5.70; found C 79.36, H 5.62%]; IR (KBr): ν˜ ϭ
3430 (OH), 1662 (br., 2 ϫ CϭO, acetyl) cmϪ1; NMR: δH
(CDCl3) ϭ 2.43 (s, 3 H, PhϪCH3), 2.55, 2.57 (2s, 2 ϫ 3 H, 2 ϫ
C(O)CH3), 10.36 (s, 1 H, OH); δC (CDCl3) ϭ 22.4 (Ph-CH3), 28.51,
28.83 [2 ϫ C(O)CH3], 153.7 (C-1-OH), 202.7, 206.6 (2 ϫ CϭO,
acetyl); m/z (EI) (%): [Mϩ], 318 (38), 257 (18), 231 (100), 204 (50).
(ii) Conversion of 9a into Isoquinolone 7c: The ylide 9a (0.3 g) was
heated under reflux in ethyl acetate (10 mL) for 30 h. After evap-
oration of the solvent in vacuo, the pale yellow solid (66 mg, 40%)
was collected in a small amount of chloroform and shown to be
identical with 7c (TLC, and comparative IR and mass spectra).
The reaction between the ylide 9 (0.3 g) and benzaldehyde (0.1 mL)
in boiling toluene (or EtOAc) (10 mL) for 45 h, was carried out
and the product mixture was worked up as above to give the isoqui-
nolone 7c (61 mg, 35%).
The reaction between equimolar amounts of 1 and 3b under the
same conditions again afforded 7d (10%), 13 (14%), and 14 (11%)
along with 1 (28%).
(iii) Alkaline Treatment of the Ylide 9a. Preparation of Compound
10: A mixture of 9a (0.3 g, 0.49 mmol) and Na2CO3 (15% aq.,
20 mL) was heated under reflux for 10 h. The mixture was cooled,
diluted with water (5 mL), and extracted with CHCl3. The residue
obtained on removal of the solvent was boiled with light petroleum
ether (40Ϫ60 °C) to afford on concentration 0.13 g of a compound,
m.p. 155 °C, shown to be Ph3PO. The insoluble portion (167 mg,
58%) was recrystallised to give the corresponding benzoylaceto-
phenone 10, m.p. 161Ϫ163 °C (CH2Cl2). [C23H19NO3 (357.41):
calcd. C 77.29, H 5.36, N 3.92; found C 77.36, H 5.42, N 3.88%];
IR (KBr): ν˜ ϭ 3424 (OH), 1731 [C-7Ϫ(O)], 1678 [C(O)Ph], 1609
(CϭN) cmϪ1; NMR: δH (CDCl3) ϭ 2.42 (s, 3 H, PhϪCH3), 2.84
(s, 2 H, CH2) 7.24Ϫ8.44 (m, 13 H, Ph-H), 8.73 (br, 1 H, NOH); δc
(CDCl3) ϭ 21.6 (Ph-CH3), 38.3 (CH2), 153.7 (CϭNOH), 166.5 [C-
7-(O)], 188.4 [C(O)Ph]; m/z (%) ϭ 357 [Mϩ] (100), 329 (13), 253
(21), 237 (100).
Treatment of 1 with Allyltriphenylphosphonium Bromide (4a). Pre-
paration of Compound 18: The oxazinone 1 (1 g, 4.22 mmol) in ethyl
methyl ketone (EMK, 20 mL) was added dropwise to a slurry of
sodium hydride (NaH) dispersion (60% in paraffin oil, 200 mg) in
the same solvent (10 mL). The reaction mixture was stirred at room
temperature until all hydrogen evolution had ceased, and the salt
4a (1.7 g, 4.5 mmol) was introduced all at once. The reaction mix-
ture was allowed to remain at room temp. for further two hours
and was then heated under reflux for 24 h. The product mixture
was concentrated to 10 mL, diluted with 30 mL of dist. H2O, acidi-
fied with conc. HCl, and then extracted with two portions of
CHCl3. The CHCl3 extracts were combined, back-washed with
100 mL of H2O and dried with anhydrous MgSO4, and the solvents
were evaporated to dryness. The residue was chromatographed on
silica gel with hexane/chloroform (3:7, v/v) and afforded colourless
crystals of 3-ethylidene-1-(4-methylphenyl)isoquinolin-4-one (18)
(680 mg, 62%), m.p. 132Ϫ133 °C (CH2Cl2). [C18H15NO (261.33):
calcd. C 82.73, H 5.78, N 5.36; found C 82.81, H 5.74, N 5.23%];
IR (KBr): ν˜ ϭ 1740 (4-CϭO), 1627 (CϭC, ethylidene), 1600 (Cϭ
N) cmϪ1; NMR: δH (CDCl3) ϭ 1.85 (d, 3 H, JH,Hϭ 7.2 Hz, ϭ
CHϪCH3), 2.43 (s, 3 H, PhϪCH3), 7.55 (q, 1 H, JH,H ϭ 7.2 Hz, ϭ
CHϪCH3), 7.34Ϫ8.42 (m, 8 H, Ph-H); δC (CDCl3) ϭ 17.6 (ϭCH-
CH3), 21.9 (Ph-CH3), 133.5 (ϭCHϪCH3), 145.3 (3-C), 192.2 (4-
CϭO); m/z (EI) (%): [Mϩ], 261 (75), 247(30), 219 (100).
(iv) Cyclization of Compound 10 to 7c: Compound 10 (0.13 g) in
polyphosphoric acid (5.0 g) was heated at 140Ϫ150 °C for 4 h. The
cooled reaction product was poured into ice-water (20 mL) and
then extracted with CHCl3. After evaporation of the dried CHCl3
solution, the residual solid was recrystallised from CH2Cl2 to give
0.05 g (49%) of colourless crystals, shown to be identical with 7c
(TLC, and comparative IR and mass spectra).
(B) Preparation of Compounds 7d, 13, and 14: A stirred mixture of
1 (1 g, 4.22 mmol) and acetylmethylenetriphenylphosphorane (3b)
(2.78 g, 8.5 mmol) in dry toluene (30 mL) containing TEA (0.5 mL)
was heated under reflux for 3 days. The product mixture was
worked up as above and gave compounds 7d, 13, and 14.
Treatment of 1 with Phosphonium Salts 4b and 4c. Preparation of
Compounds 21a and 21b: A solution of the appropriate salt 4b (3 g,
8.5 mmol) or 4c (3.2 g, 8.5 mmol) and 1 (1 g, 4.22 mmol) in EMK
(30 mL) was treated with NaH under the experimental conditions
described for the salt 4a. The reaction mixture was heated under
3-Acetyl-1-(4-methylphenyl)-3H-isoquinolin-4-one (7d): This com-
pound was obtained (hexane/ethyl acetate, 3:7, v/v) as colourless
crystals (140 mg, 12%), m.p. 156Ϫ158 °C (acetonitrile). reflux for ca. 18 h (TLC) and then worked up as described for 4a
[C18H15NO2 (277.39): calcd. C 77.94, H 5.45, N 5.07; found C and chromatographed with hexane/CHCl3 to give 21a (3:7, v/v) or
77.99, H 5.48, N 5.02%]; IR (KBr): ν˜ ϭ 1762 (4-CϭO), 1675 (Cϭ
21b (2:8, v/v), respectively.
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Eur. J. Org. Chem. 2002, 1696Ϫ1701