Novel synthesis route for pyrrolo[1,2-a]quinazolines

Full text of DOI:10.1023/B:COHC.0000033556.58356.5c

Chemistry of Heterocyclic Compounds, Vol. 40, No. 4, 2004
NOVEL SYNTHESIS ROUTE
FOR PYRROLO[1,2-a]QUINAZOLINES
E. S. Vostrov, D. V. Gilev, and A. N. Maslivets
Keywords: 2-aroylmethylene-3-aryl-4-quinazolones, hetereno[a]-2,3-dihydro-2,3-pyrrolediones.
3-Phenacylidene-1,2,3,4-tetrahydro-2-quinoxalones react with oxalyl chloride to form substituted
3-aroyl-1,2,4,5-tetrahydropyrrolo[1,2-a]quinoxaline-1,2,4-triones [1], while 2-phenacylidene-1,2-dihydro-
quinoxalines react to form 5-aryl-4-quinoxalinyl-2,3-dihydro-2,3-furandiones [2]. With the aim of extending the
data so we can predict which of the two directions indicated above will occur, we undertook the synthesis of
2-phenacylidene-3-aryl-1,2,3,4-tetrahydro-4-quinazolones 2a,b and studied their reaction with oxalyl chloride.
The structure of the substituted quinazolones 2a,b is the limiting factor for realization of one of the alternative
directions for reaction of a heterocyclic enaminoketone with oxalyl chloride.
Usually 2-acylmethylene-3-aryl-4-quinazolones are obtained by reaction of 2-(methyl lithium)-3-aryl-4-
quinazolones with esters [3] or ester condensation of 2-(methyl lithium)-3-aryl-4-quinazolones in the presence of
sodium hydride [4]. We propose a novel and simple method for obtaining substituted quinazolones 2a,b by
reaction of 2-phenacylidene-3,4-dihydro-1H-3,1-benzoxazin-4-one (1) with aromatic amines. When substituted
quinazolones 2a,b react with oxalyl chloride under conventional conditions for synthesis of five-membered
2,3-dioxo heterocycles [1, 2], instead of the expected 3-aryl-2-(4,5-dioxo-2-phenyl-4,5-dihydro-3-furyl)-3,4-
dihydro-4-quinazolones (3a,b), we get 4-aryl-3-benzoyl-1,2,4,5-tetrahydropyrrolo[1,2-a]quinazoline-1,2,5-
triones (4a,b).
O
O
Ar
O
N
O
O
N
H
N
O
.
.
1
.
O
Ph
Ph
ArNH2
3a,b
∆
O
N
O
Ar
Ar
N
(COCl)2
N
COPh
N
H
.
.
.
O
O
Ph
O
2a,b
4a,b
2–4 a Ar = Ph, b Ar = o-MeC6H4
__________________________________________________________________________________________
Perm State Pedagogical University, Perm 614990, Russia; e-mail: koh2@psu.ru. Translated from
Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 629-630, April, 2004. Submitted November 21, 2003.
532
0009-3122/04/4004-0532©2004 Plenum Publishing Corporation

In the indicated reaction, probably closure of the pyrroledione ring occurs due to its greater
thermodynamic stability compared with the alternative furandione ring, while in our case steric hindrances
leading to closure of the furandione ring are not as important as in the case described in [2]. The described
reaction is a novel route to constructing a heterocyclic system of a substituted pyrrolo[1,2-a]quinazoline.
E-2-Phenacylidene-3-phenyl-1,2,3,4-tetrahydro-4-quinazolone (2a). A solution of benzoxazinone 1
(0.50 g, 1.88 mmol) and aniline (0.17 ml, 1.88 mmol) in decane (1 ml) was boiled for 1 h and then cooled down.
The precipitate was filtered out. Yield 0.60 g (93%); mp 212-214°C (2-propanol). IR spectrum (vaseline oil),
ν, cm-1: 3040 broad (NH in the intramolecular hydrogen bond), 1685 (C(4)=O), 1610 broad (COPh in the
1
intramolecular hydrogen bond). H NMR spectrum (250 MHz, DMSO-d6), δ, ppm (J, Hz): 5.04 (1H, s,
C(2)=CH); 7.30-7.85 (13H, m, ArH); 8.07 (1H, d, J = 8.0, C(5)H); 15.60 (1H, s, NH). Found, %: C 77.67; H 4.73;
N 8.25. C22H16N2O2. Calculated, %: C 77.63; H 4.74; N 8.23.
E-2-Phenacylidene-3-o-tolyl-1,2,3,4-tetrahydro-4-quinazolone (2b) was synthesized similarly.
Yield 0.60 g (90%); mp 218-219°C (2-propanol). IR spectrum (vaseline oil), ν, cm-1: 3060 broad (NH in the
intramolecular hydrogen bond), 1683 (C(4)=O), 1615 broad (COPh in the intramolecular hydrogen bond).
1H NMR spectrum (400 MHz, DMSO-d6), δ, ppm (J, Hz): 2.12 (3H, s, Me); 4.96 (1H, s, C(2)=CH); 7.30-7.90
(12H, m, ArH); 8.05 (1H, d, J = 7.9, C(5)H); 15.38 (1H, s, NH). Found, %: C 77.95; H 5.05; N 7.94. C23H18N2O2.
Calculated, %: C 77.97; H 5.08; N 7.91.
3-Benzoyl-4-phenyl-1,2,4,5-tetrahydropyrrolo[1,2-a]quinazoline-1,2,5-trione (4a). A solution of
quinazolone 1a (0.10 g, 0.29 mmol) and oxalyl chloride (0.03 ml, 0.29 mmol) in absolute chloroform (3 ml) was
boiled for 30 min under reflux and then cooled down. The precipitate was filtered out. Yield 0.10 g (95%);
mp 255-256°C (with decomposition, from chloroform). IR spectrum (vaseline oil), ν, cm-1: 1790 (C(1)=O), 1728
1
(C(2)=O), 1716 (C(5)=O) 1648 (COPh). H NMR spectrum (500 MHz, DMSO-d6), δ, ppm (J, Hz): 7.03-7.95
(12H, m, ArH); 8.11 (1H, d, J = 7.9, C(6)H); 8.68 (1H, d, J = 8.0, C(9)H). Found, %: C 73.07; H 3.52; N 7.10.
C24H14N2O4. Calculated, %: C 73.10; H 3.55; N 7.11.
3-Benzoyl-4-o-tolyl-1,2,4,5-tetrahydropyrrolo[1,2-a]quinazoline-1,2,5-trione (4b) was synthesized
similarly. Yield 0.11 g (93%); mp 230-232°C (with decomposition, from chloroform). IR spectrum (vaseline
oil), ν, cm-1: 1783 (C(1)=O), 1725 (C(2)=O), 1712 (C(5)=O), 1650 (COPh). 1H NMR spectrum (400 MHz, CDCl3),
δ, ppm (J, Hz): 2.23 (3H, s, Me); 7.11-7.85 (11H, m, ArH); 8.23 (1H, d, J = 7.9, C(6)H); 8.82 (1H, d, J = 8.0,
13
C(9)H). C NMR spectrum (100 MHz, CDCl3), δ, ppm: 17.79 (Me); 114.32 (C(9)); 126.25-137.21 (Ar); 156.78
(C(1)); 157.49 (C(5)); 161.71 (C(3a)); 173.49 (C(2)), 186.50 (COPh). Found, %: C 73.50; H 3.95; N 6.88.
C25H16N2O4. Calculated, %: C 73.53; H 3.92; N 6.86.
This work was carried out with the financial support of the Russian Foundation for Basic Research
(grants Nos. 01-03-32641, 02-03-96411, 03-03-06634). The NMR spectra were taken at the Ural Regional NMR
Spectroscopy Center, URAL-NMR (Russian Foundation for Basic Research grant No. 00-03-40139).
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