Behavior of 3-Amino-2-phenyl-4(3H)-quinazolinone
983
(NH), 1686, 1515 (C¼P), 1432, 985 (P–C, phenyl) cmꢂ1
;
Reaction of Compound 1 with Ethoxycarbonylmethylene
triphenylphosphorane (3a)
1H NMR (270MHz, CDCl3): ꢀ ¼ 8.72, 8.75 (2s, NH2),
4
8.43 (d, NH, JHP ¼ 10 Hz), 6.72–7.35 (m, Ar) ppm; 13C
A mixture of 1 mmol 1 and 1 mmol phosphonium ylide 3a in
30cm3 dry toluene was refluxed for 6 h. The volatile materials
were evaporated under reduced pressure. The residue was
subjected to silica gel column chromatography to give 6.
2
NMR (270MHz, CDCl3): ꢀ ¼ 118.2 (C ¼ N, JCP ¼ 26.1Hz),
1
2
105.83 (C ¼ P, JCP ¼ 115 Hz), 69.55 (N–C–N, JCP
¼
22.0Hz), 165.22 (NC¼O), 128.12, 117.15, 132.62, 112.65
(4CH, Ar), 117.31, 142.32 (C¼C, Ar), 142.45, 127.12,
128.34, 126.52 (Ph), 128.37, 131.26, 129.05, 126.24 (PPh3)
ppm; 31P NMR (270 MHz, CDCl3): ꢀ ¼ þ21.75ppm; MS
(EI): m=z (%) ¼ 538 (Mþ, 100).
3a-Phenyl-3-(triphenylphosphoranylidene)-3a,4-
dihydropyrazolo[5,1-b]-quinazolin-2,9(1H,3H)-dione
(6, C34H26N3O2P)
Eluent: petroleum ether=acetone (70=30, v=v). Product 6 was
separated as white crystals, yield 80%; mp 221ꢁC; IR (KBr):
ꢁꢀ¼ 1666 (CO–NH), 3254 (b, 2NH), 1680, 1510 (C¼P) and
Reaction of Tris(dialkylamino)phosphines 4a and 4b with
3-Amino-2-phenyl-4(3H)-quinazolinone (1)
A suspension of 0.23g 1 (1mmol), 1 cm3 tris(dialkylamino-
phosphines 4a or 4b was heated in an oil bath at 110ꢁC for 8 h.
The reaction mixture was evaporated under reduced pressure.
The residue was subjected to silica gel column chromatogra-
phy to give products 9a and 9b.
1
at 1430, 990 (P–C, phenyl) [23] cmꢂ1; H NMR (270MHz,
CDCl3): ꢀ ¼ 6.61–7.30 (m, 24H, Ar), 8.55, 8.64 (d, 2H, NH,
JHP ¼ 8 Hz) ppm; 13C NMR (270MHz, CDCl3): ꢀ ¼ 122.29
(d, 1JCP ¼ 124.45 Hz, C¼P), 168.59 (d, 2JCP ¼ 33.7Hz, C¼O),
164.96 (s, C¼O), 128.22, 116.70, 132.25, 113.53 (4CH, Ar),
115.13, 147.25 (C¼C, Ar), 144.52, 127.10, 128.32, 126.25
(4CH, Ph), 128.74, 131.30, 128.52, 129.03 (PPh3) ppm;
31P NMR (270MHz, CDCl3): ꢀ ¼ þ26.21 ppm; MS (EI):
m=z (%) ¼ 539 (Mþ, 90).
3-Amino-4-hydroxy-2-phenyl-3,4-dihydro-quinazolin-4-yl)-
(dimethylamino)oxophosphonium (9a, C16H17N4O2P)
Eluent: petroleum ether=acetone (50=50, v=v). Product 9a was
separated as colorless crystals, yield 75%; mp 215ꢁC; IR (KBr):
ꢁꢀ¼ 1580 (C¼N), 1240 (P¼O), 1320, 860 [P–N(CH3)2]
Similarly, product 6 was obtained by the reaction of me-
thoxycarbonylmethylenetriphenylphosphorane (3b) with 1.
1
3230 (NH2) cmꢂ1; H NMR (270MHz, CDCl3): ꢀ ¼ 2.43 [d,
JHP ¼ 10Hz, PN(CH3)2], 7.05–7.62 (m, 9H, Ar), 8.65, 8.68
(2s, NH2) ppm; 13C NMR (270 MHz, CDCl3): ꢀ ¼ 165.64
(C¼O), 119.73 (¼C–CO), 139.50 (¼C–N), 76.46 (N–C–P),
25.72, 25.72 [P–(NCH3)2], 139.60, 128,63, 127,08, 127.43
(C6H5), 127.45, 119.50, 137.65, 115.34 (4CH, Ar) ppm;
31P NMR (270MHz, CDCl3): ꢀ ¼ þ50 ppm; MS (EI): m=z
(%) ¼ 328 (Mþ, 100).
General Procedure for the Reaction of Phosphonium Ylides
3c, 3d with Quinazolinone 1
A mixture of 1 mmol 3c and 3d and 1 mmol quinazolinone 1
in 30 cm3 dry toluene was refluxed for 8 h. The volatile mate-
rials were evaporated under reduced pressure. The residue was
subjected to silica gel column chromatography to give prod-
ucts 7 and 8.
3-Amino-4-hydroxy-2-phenyl-3,4-dihydro-quinazolin-4-yl)-
(diethylamino)oxophosphonium (9b, C18H21N4O2P)
(3-Amino-4-oxo-2-phenyl-1,2,3,4-tetrahydroquinazolin-2-yl)-
(triphenylphosphoranylidene)acetaldehyde (7, C34H28N3O2P)
Eluent: petroleum ether=acetone (85=15, v=v). Product 7
was separated as colorless crystals, yield 75%; mp 237ꢁC;
IR (KBr): ꢁꢀ¼ 1718 (C¼O, aldehyde), 1656 (C¼O, O¼C–
N–NH2) 1674, 1530 (C¼P), 1448, 928 (P–C, phenyl), 3230
Eluent: petroleum ether=acetone (75=25, v=v). Product 9b
was separated as colorless crystals, yield 80%; mp 211ꢁC;
IR (KBr): ꢁꢀ¼ 1585, 1245 (P¼O), 1315, 870 [P–N (C2H5)2],
1
3240 (NH2) cmꢂ1; H NMR (270 MHz, CDCl3): ꢀ ¼ 1.94 (t,
3
6H, P[N–CH2CH3)2], 2.35 {q, 4H, P[N(CH2CH3)2], JHP
¼
(NH2), 3254 (NH) cmꢂ1
;
1H NMR (270 MHz, CDCl3):
10Hz}, 6.80–7.73 (m, 9H, Ar), 8.0, 8.15 (2s, NH2) ppm; MS
(EI): m=z (%) ¼ 356 (Mþ, 95).
2
ꢀ ¼ 9.95 (d, 1H, O¼CH–C¼P, JHP ¼ 30 Hz), 8.30 (d,
4
1H, NH, JHP ¼ 10 Hz), 8.65, 8.70 (2s, NH2), 6.90–7.90
(m, 24H, Ar) ppm; 13C NMR (270 MHz, CDCl3): ꢀ ¼
193.05 (d, 2JCP ¼ 27.0 Hz, CHO), 115.30 (d, 1JCP ¼ 120 Hz,
2
References
C¼PPh3), 54.73 (d, JCP ¼ 25.0 Hz, C–C¼P), 164.52
(NC¼O), 113.37, 113.23, 117.45, 128.50 (4CH, Ar), 115.35,
147.43 (C¼C, Ar), 144.32, 127.23, 128.42, 126.50 (Ph),
128.37, 132.05, 129.13, 127.05 (PPh3) ppm; 31P NMR
(270 MHz, CDCl3): ꢀ ¼ þ22.7 ppm; MS (EI): m=z (%) ¼
541 (Mþ, 90).
[1] Bartroli J, Turmo E, Alguero M, Boncompte E, Vericat
ML, Conte L, Ramis J, Merlos M, Garcia-Rafanell J,
Forn (1998) J Med Chem 41: 1869
[2] Shiba SA, El-Khamry AA, Shaban ME, Atia KS (1997)
Pharmazie 52: 189
[3] Abdel-Hamid SG (1997) J Ind Chem Soc 74: 613
[4] Barker A (1995) J Eur Pat 635498; Chem Abstr 122:
214099
(3-Amino-4-oxo-2-phenyl-1,2,3,4-tetrahydroquinazolin-2-
yl)(triphenylphosphoranylidene)acetonitrile
(8, C34H27N4OP)
[5] Bekhit AA, Khalil MA (1998) Pharmazie 53: 539
[6] Gursoy A, Karali N (1995) Farmaco 50: 857
[7] Nawrocka W, Zimecki M (1997) Arch Pharm 330:
399
Eluent: petroleum ether=ethyl acetate (50=50, v=v). Product 8
was separated as colorless crystals, yield 80%; mp 243ꢁC;
IR (KBr): ꢁꢀ¼ 1660 (C¼O, O¼C–N–NH2) 2200 (CN), 3250