July 2012
Conversion of Some 2(3H)-Furanones into Pyrrolinotriazine
949
and Oxazolopyrimidine Derivatives
2-(3-((1H-indol-3-yl)methylene)-2-oxo-5-phenyl-2,3-dihydropyrrol-
1-yl)acetic acid (3b). Bright yellow crystals (75% yield), m.p
115–117ꢀC. IR: nmax 3,250–3,420 (OH), 3,300 (NH), 1,700,
inferred from their analytical, as well as, spectral data
(cf. Experimental section).
1,640 (C═O) cmÀ1 1H NMR (DMSO-d6): d 3.90 (s, 2H,
.
CH2COOH), 6.54 (s, 1H, HC═), 6.90–7.99 (m, 12H, 11ArH +
NH), 12.01 (br.s, 1H, OH, exchangeable). Anal. Calcd. for
C21H16N2O3: C, 73.24; H, 4.68; N, 8.13. Found: C, 73.40; H,
4.81; N, 8.24.
EXPERIMENTAL
Melting points were measured on an electrothermal melting
point apparatus. Elemental analyses were performed using a
Heraeus CHN rapid analyzer at the Microanalytical unit, Cairo
University. IR spectra were measured on a Unicam SP-1200
spectrophotometer using KBr wafer technique. H NMR spec-
tra were measured in DMSO-d6 on a Varian plus instrument
(300 MHz).
General procedure for the preparation of 5-phenyl-3-
heterylmethylene-2(3H)-furanones (1). These compounds were
prepared according to the procedure described by previous
investigators [10–12].
General procedure for the preparation of 3-benzoyl-2-
heterylmethylene propionic acid hydrazides (5). These
compounds were prepared according to the procedure described
by previous investigators [1,5].
General procedure for the reaction of the 5-phenyl-3-
heterylmethylene-2(3H)-furanones 1 with glycine. A suspension
of the furanones 1 (1 mmol) and glycine (2 mmol) in (20 mL)
ethanol were refluxed at 70ꢀC for 6 h and left to cool. The
solid obtained was filtered off, washed, and recrystallized
from ethanol and was found to be 2-(2-heterylmethylene-4-
oxo-4-phenylbutanamido) acetic acid 2.
General procedure for the preparation of pyrrolotriazinone
derivatives (4). A mixture of pyrrolin-5-one derivatives 3
(1 mmol) and thionyl chloride (20 mL, 0.17 mol) was
refluxed for 3 h. The excess thionyl chloride was then evaporated
under vacuum. The oily product obtained was dissolved in
ethanol (20 mL), and 4 mL of hydrazine was added. The reaction
mixture was heated under reflux for 2 h and left to cool. The solid
obtained was filtered off, washed and recrystallized from ethanol
and was found to be 8-heterylmethylene-6-phenylpyrrolo[2,1-c]
[1,2,4]triazin-3(2H, 4H, 8H)-one 4.
8-(Furan-2-ylmethylene)-6-phenylpyrrolo[2,1-c][1,2,4]triazin-
3(2H, 4H, 8H)-one (4a). Yellow crystals (60% yield), m.p
250–252ꢀC. IR: nmax 3,210 (NH), 1,631 (C═O) cmÀ1. 1H NMR
(DMSO-d6): d 3.62 (s, 2H, CH2CO), 6.62 (s, 1H, CH═),
6.80–7.56 (m, 9H, ArH), 8.32 (s, 1H, NH―CO, exchangeable).
Anal. Calcd. for C17H13N3O2: C, 70.09; H, 4.50; N, 14.42.
Found: C, 70.21; H, 4.68; N, 14.67.
1
8-((1H-indol-3-yl)methylene)-6-phenylpyrrolo[2,1-c][1,2,4]
triazin-3(2H, 4H, 8H)-one (4b). Yellow crystals (65% yield),
m.p 300–302ꢀC. IR: nmax 3,200, 3,210 (NH), 1,640 (C═O)
cmÀ1 1H NMR (DMSO-d6): d 3.60 (s, 2H, CH2CO), 6.66
.
2-(2-(Furan-2-ylmethylene)-4-oxo-4-phenylbutanamido)
acetic acid (2a). Colorless crystals (60% yield), m.p 170–172ꢀC.
IR: nmax 3,150–3,500 (OH), 3,320 (NH), 1,700, 1,680, 1,630
(s, 1H, HC═), 6.80–7.86 (m, 12H, 11ArH + NH), 8.21 (br.s,
1H, NH, exchangeable). Anal. Calcd. for C21H16N4O: C,
74.10; H, 4.74; N, 16.46. Found: C, 73.95; H, 4.91; N, 16.63.
General procedure for the reaction of hydrazides 5 with
NaNO2/AcOH. To a solution of hydrazide 5 (2 gm) in AcOH
(20 mL) cooled in an ice-bath at 5ꢀC, a cold NaNO2 solution
was added dropwise while stirring. After complete addition,
the reaction mixture was left at room temperature for 30 min
and then poured into ice-cold water. The crystals separated
were filtered-off, washed with cold water, and found to be 1-
azido-2-heterylmethyl-4-phenylbutane-1,4-dione 6.
(C═O) cmÀ1. H NMR (DMSO-d6): d 3.19 (s, 2H, CH2―CO),
1
3.95 (s, 2H, CH2―COOH), 6.50 (s, 1H, HC═), 7.01–7.98 (m,
8H, ArH), 8.12 (br.s, 1H, NH, exchangeable), 12.01 (br.s, 1H,
OH, exchangeable). Anal. Calcd. for C17H15NO5: C, 65.17; H,
4.83; N, 4.47. Found: C, 65.41; H, 4.65; N, 4.61.
2-(2-((1H-indol-3-yl)methylene)-4-oxo-4-phenylbutanamido)
acetic acid (2b). Colorless crystals (50% yield), m.p 140–141ꢀC.
IR: nmax 3,220–3,500 (OH), 3,300 (NH), 1,705, 1,677, 1,640
(C═O) cmÀ1 1H NMR (DMSO-d6): d 3.22 (s, 2H, CH2CO),
.
3.91 (s, 2H, CH2―COOH), 6.52 (s, 1H, HC═), 6.97–8.03
(m, 11H, 10ArH NH), 8.23 (br.s, 1H, NH―CO,
1-Azido-2-(furan-2-ylmethylene)-4-phenylbutane-1,4-dione
(6a). Yellow crystals (52% yield), m.p 94–96ꢀC. IR: nmax 2,150
+
(N3), 1,760, 1,710 (C═O) cmÀ1 1H NMR (DMSO-d6): d 3.22
.
exchangeable), 11.95 (br.s, 1H, OH, exchangeable). Anal.
Calcd. for C21H18N2O4: C, 69.60; H, 5.01; N, 7.73.Found:
C, 69.89; H, 4.77; N, 7.92.
General procedure for the ring closure of compounds
(2). A solution of 2 (1 gm) in a mixture of (HCl-AcOH) (1:1)
(30 mL), was heated under reflux for 1 h and then left to
cool. The solid obtained was collected by filtration, washed
with water and recrystallized from benzene/ethanol to give
pyrrolone derivatives 3.
(s, 2H, CH2CO), 6.60 (s, 1H, HC═), 7.21–7.88 (m, 8H, ArH).
Anal. Calcd. for C15H11N3O3: C, 64.05; H, 3.94; N, 14.94.
Found: C, 64.23; H, 3.71; N, 15.02.
1-Azido-2-((1H-indol-3-yl)methylene)-4-phenylbutane-1,4-
dione (6b). Yellow crystals (50% yield), m.p 114–116ꢀC. IR:
1
nmax 2,120 (N3), 1,757, 1,712 (C═O) cmÀ1. H NMR (DMSO-
d6): d 3.20 (s, 2H, CH2CO), 6.62 (s, 1H, HC═), 7.30–8.11
(m,11H, 10ArH + NH). Anal. Calcd. for C19H14N4O2:
C, 69.08; H, 4.27; N, 16.96. Found: C, 69.27; H, 4.35; N, 17.10.
General procedure for the reaction of azido compounds
6 with glycine. The azido compound 6 (1 mmol) and glycine
(1mmol) in 10 mL of dry benzene was heated under reflux
for 1 h. The reaction mixture was concentrated, and the solid
product obtained was filtered off and recrystallized from
benzene/ethanol and was found to be ureido acetic acid
derivatives 7.
The same products 3 were obtained when furanones 1
(1 mmol) and glycine (2 mmol) were refluxed in acetic acid
(10 mL) for 10 hrs and then poured into ice-cold water. The crys-
tals separated were filtered off and recrystallized from ethanol.
2-(3-(Furan-2-ylmethylene)-2-oxo-5-phenyl-2,3-dihydropyrrol-
1-yl)acetic acid (3a). Bright yellow crystals (70% yield), m.p
130–131ꢀC. IR: nmax 3,200–3,450 (OH), 1,700, 1,641 (C═O)
cmÀ1. H NMR (DMSO-d6): d 3.92 (s, 2H, CH2COOH), 6.50
1
(s, 1H, HC═), 6.65–7.89 (m, 9H, ArH), 12.01 (br.s, 1H, OH,
exchangeable). Anal. Calcd. for C17H13NO4: C, 69.15; H,
4.44; N, 4.74. Found: C, 68.93; H, 4.60; N, 4.89.
2-(3-(1-(Furan-2-yl)-4-oxo-4-phenylbut-1-en-2-yl)ureido)
acetic acid (7a). Brown crystals (45% yield), m.p 224–226ꢀC.
IR: nmax 3,300–3,450 (OH), 3,320 (NH), 1,705, 1,680, 1,632
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet