I? Molina, A. Alias, A. Balado, A. Arques 745

Notiz / Note

Iminophosphorane-Mediated Synthesis of Fused Perimidines: Preparation of Quinazolino[3,4-a]perimidine Derivatives Pedro Molina", Asunci6n Alias, Ana Balado and Antonio Arques

Departamento de Quimica Organica, Facultad de Quimica, Universidad de Murcia, Campus de Espinardo, E-30071, Murcia, Spain

Received February 7, 1994

Key Words: Aza Wittig reaction I Heterocumulene-mediated annulation I Perimidines, fused

An aza-Wittig-type reaction of iminophosphoranes 2 and 3, derived from 2-(2-azidophenyl)-l,2-dihydroperimidine and 2-(2-azidophenyl)perimidine, respectively, with isocyanates,

carbon dioxide, carbon disulfide and acyl chlorides provides 6-substituted quinazolino[3,4-a]perimidines 4-10.

The heteroaromatic system perimidine exhibits simultaneously the distinct properties of compounds with an excess and a de- ficiency of K electrons, together with a wide variety of practical applications[']. In spite of the extensive work spent on the prep- aration of perimidine derivatives, only a few methods of the syn- thesis of fused perimidines, namely quinazolino[3,4-~]perimidines have been reported until now. It has only been briefly mentioned that treatment of 2-(2-aminophenyl)perimidine with either chloro- thioformyl chloride['] or aromatic aldehydes and further oxi- dationl3] provide quinazolin0[3,4-~]perimidines. Reaction of 2-iso- cyanatobenzoyl chloride with 1,s-diaminonaphthalene affords 5H- 6-oxoquinazolino[3,4-u]perimidine in moderate yieldL4]. The main disadvantage of these methods is that the scope for the introduction of different substituents is limited. We now report on a general synthesis of functionalized quinazolin0[3,4-~]perimidines which is capable of modification to allow the introduction of a wide range of substituents. Our approach is based on an efficient application of the aza-Wittigheterocumulene-mediated annulation strategy in- volving the NH group of the perimidine ring. Although a wide variety of nitrogen-containing heterocycles have been prepared by means of this methodol0gy~~1, no examples involving pyrimidine- like amino groups have been reported.

The Staudinger reaction of 1,2-dihydroproperimidine 1, readily available in 78% yield by condensation of 1,s-diaminonaphtalene with o-azidobenzaldehyde[6], with triphenylphosphane at room temperature provides the iminophosphorane 2 in 87% yield, which undergoes dehydrogenation by the action of 10% P d C to give the iminophosphorane 3 in 80% yield (Scheme 1).

An aza-Wittig-type reaction of iminophosphorane 2 with aro- matic isocyanates in dry dichloromethane at reflux temperature di- rectly affords 6-arylamino-14,14a-dihydroquinazolino[3,4-u]perimi- dines 4 in moderate yields (45-51%). Likewise, reaction with car- bon dioxide or carbon disulfide in a sealed tube at 100°C provides the 6-0x0 or 6-thioxo derivatives 5 and 6, respectively, in good yields (Scheme 2).

On the other hand, iminophosphorane 3 reacts with aromatic and aliphatic isocyanates in dichloromethane at room temperature to give 6-alkyl(aryl)aminoquinazolino[3,4-u]perimidines 8 in good yields, while iminophosphorane 3 does not react with aroyl chlor- ides in the presence of triethylamine in toluene at reflux tempera-

Scheme 1

1 2

p N = P P h .

N ' N X H 10% Pd/C, toluene, reflux,

8041~

3

Scheme 2

Ar-NCO CH2CIZ, reflux

2 c 45-5 1 %

'NH-Ar

1 67-75% 4

ture even after prolonged reaction time; in a sealed tube at 160°C the 6-aryl-substituted quinazolino[3,4-u]perimidines 7 were ob-

Liebigs Ann. Chem. 1994,745-749 0 VCH Verlagsgesellschaft mbH, D-69451 Weinheim, 1994 0170-2041/94/0707-0745 $10.00+.2510

746 I? Molina, A. Alias, A. Balado, A. Arques

tained in moderate yields. These rigorous reaction conditions sug- gest that the conversion of 3 to 7 involves initial acylation of the perimidine ring instead of formation of an imidoyl chloride by an aza Wittig reaction between the iminophosphorane moiety and the acyl chloride[']. Finally, intramolecular aza Wittig reaction between the carbonyl group of the amide function and the iminophos- phorane provides the cyclized product 7. Iminophosphorane 3 also reacts with carbon dioxide and carbon disulfide to give 9 and 10, respectively, in excellent yields (Scheme 3). Structural elucidation of compounds 4-10 has been accomplished on the basis of their analytical and spectral data.

Scheme 3

7 8

q-5 10 s

a: Ar-COC1, Et3N, toluene, sealed tube, 160°C; yield 40-57%. - b: R-NCO, CH2C12, room temperature; yield 43-79%. - c: CX2, sealed tube, 100°C; yield 85-90%.

The authors are indebted to Direccidn General de Znvestigacion Cientifica y Ticnica for financial support (Project Number PB92- 0984).

Experimental Melting points (uncorrected): Kofler hot-stage apparatus. - IR:

Nicolet FT 5DX; nujol emulsions in NaCl plates. - 'H and I3C NMR: Bruker AC 200. - MS (EI, 70 eV): Hewlett-Packard 5993C. - CC: Silica gel 60 (Co. Merck); columns of 4.5 cm diameter and 70 cm height were used.

2-(2-Azidopheny1)-2,3-dihydro-lH-perimidine (1): To a mixture of o-azidobenzaldehyde (2.94 g, 20 mmol), acetic acid (2 ml) and dry Et20 (40 ml) were added in one portion to a solution of 1,8- diaminonaphthalene (3.16 g, 20 mmol) in the same solvent (20 ml). The resultant solution was stirred at 0°C for 1 h, then allowed to warm to room temp. The solvent was removed under reduced press- ure, and the residual material was suspended in cold n-hexane (2 X 10 ml). The resultant solid was recrystallized from CH2C12/Et20 (1 : 1, vlv) to give 1; yield 4.47 g (78%), colorless prisms, m.p. 97°C. - IR: 0 = 3364 cm-' (NH), 2129, 2095, 1602, 1428, 1298, 1259,

IH, 3J = 7.8 Hz, 4J = 1.4 Hz), 7.36 (dt, l H , 3J = 7.3 Hz, 4J = 1.7 Hz), 7.25-7.14 (m, 6H), 6.50 (dd, 2H, 3J = 6.8 Hz, 4J = 1.4 Hz), 5.75 (s, lH), 4.54 (br. s, 2H, NH). - I3C NMR (CDC13): 6 = 141.57 (q), 137.82 (q), 134.74 (q), 131.44 (4). 130.00, 128.44,

1164, 1086, 1072, 809, 753. - 'H NMR (CDCl3): 6 = 7.70 (dd,

126.81, 125.30, 118.04, 117.81, 113.30 (q), 106.02, 61.72. - MS:

rnlz (%) = 287 (39) [M+], 258 (100). - Cl7HI3N5 (287.3): calcd. C 71.07, H 4.56, N 24.37; found C 70.95, H 4.61, N 24.18.

2-[2- ( Triphenylphosphoranilideneamino)phenyl]-2,3-dihydro-l H- perimidine (2): To a stirred solution of 1 (2.87 g, 10 mmol) in anhy- drous CH2C12 (30 ml) at 0°C was added dropwise a solution of triphenylphosphane (2.62 g, 10 mmol) in the same solvent under nitrogen. The reaction mixture was allowed to warm to room temp. and stirred for 16 h. The solvent was removed under reduced press- ure, and the residue was recrystallized from CH2Clz/Et20 (1 : 1, v/ v) to give 2; yield 4.53 g (87%), colorless prisms, m.p. 198°C. - IR: it = 3352 cm-I, 1598, 1436, 1414, 1341, 1315, 1108, 1021,821,757, 742, 722, 693. - 'H NMR (CDC13): 6 = 7.75-7.68 (m, 6 H), 7.52-7.31 (m, 10 H), 7.25-7.15 (m, 5 H), 6.87 (t, 1 H, 3J = 7.8 Hz), 6.69 (t, 1 H, 3J = 7.3 Hz), 6.51-6.46 (m, 2 H), 6.18 (s, 1 H), 5.41 (br. s, 2 H, NH). - 13C NMR (CDCI3): 6 = 148.88 (q), 143.05 (q), 134.97 (q), 133.46 (q, 3Jp = 21.2 Hz), 132.40 (*JP = 10.1 Hz), 131.88 (4Jp = 2.5 Hz), 130.71 (q, 'JP = 100.2 Hz), 128.79 (3Jp = 11.6 Hz), 128.22, 126.78, 125.43 (4Jp = 2.5 Hz), 121.07 (3Jp = 10.1 Hz), 117.58, 116.96, 113.88 (4). 105.84, 64.51. - MS: mlz (YO) = 521 (2) [M+], 259 (100). - C35H28N3P (521.6): calcd. C 80.60, H 5.41, N 8.06; found C 80.78, H 5.28, N 8.25.

2-[2- ( Triphenylphosphoranylideneamino)phenyl]-1 H-perimidine (3): To a suspension of iminophosphorane 2 (2.60 g, 5 mmol) in anhydrous toluene (75 ml) was added palladium on charcoal (0.3 g). The mixture was stirred at reflux temperature for 20 h. After cooling, the mixture was filtered through Celite, and the solvent was removed from the filtrate to give a crude product, which was recrystallized from CHzC1z/EtzO (l: l , vlv) to give 3; yield 2.07 g (SO%), yellow prisms, m.p. 210-211°C. - IR: 0 = 3408 cm-', 1623, 1578, 1438, 1321, 1280, 1161, 1107, 1008,769, 749,720, 693,

7.79-7.68 (m, 8 H), 7.61-7.54 (m, 4 H), 7.51-7.44 (m, 7 H), 7.02 (br. s, 1 H, NH), 6.94-6.87 (m, 3 H), 6.77 (t, 1 H, 3J = 7.2 Hz),

149.93 (q, 2Jp = 3.4 Hz), 143.05 (q), 135.76 (q), 132.61 (2Jp = 10.1 Hz), 132.50 (4Jp = 2.0 Hz), 130.54, 130.26 (4Jp = 2.1 Hz), 129.12 (3Jp = 12.1 Hz), 128.16, 122.86 (3Jp = 12.2 Hz), 118.21, 117.61, 117.58, 116.96 (9). - MS: rnlz (%) = 519 (3) [M+], 183 (100). - C35H26N3P (519.6): calcd. C 80.91, H 5.04, N 8.09; found C 81.14, H 4.95, N 8.27. 6-Arylarnino-l4,14a-dihydroquinazolino[3,4-a]perimidines (4). -

General Procedure: To a solution of iminophosphorane 2 (0.52 g, 1 mmol) in anhydrous CH2CI2 (20 ml) was added the appropriate isocyanate (1 mmol). The resultant solution was stirred at reflux temperature for 24 h. After cooling, the solvent was removed under reduced pressure, and the solid residue was chromatographed on silica gel (70-230 mesh; column 40 X 3.5 cm) using EtOAchexane (1 : 1) as eluent to give 4 which was recrystallized from CH2C12.

6-Phenylamino-14,14a-dihydroquinazolino[3,4-a]perimidine (4a): Yield 0.16 g (45%), colorless prisms, m.p. 179-180°C. - IR: 5 = 3415 cm-', 1634. - 'H NMR (CDCI3): 6 = 7.68 (d, 1 H, 3J = 8.4 Hz), 7.50-7.25 (m, l lH) , 7.03-6.96 (m, 3H), 6.65 (dd, l H , 3J =

619. - 'H NMR (CDCl3): 6 = 8.50 (d, l H , 3J = 7.8 Hz),

6.47 (d, 1 H, 3J = 8.1 Hz). - 13C NMR (CDCl3): 6 = 155.37 (4).

5.1 Hz, 4J = 3.3 Hz), 5.85 (s, 1 H), 4.54 (s, 1 H, NH). - 13C NMR (CDC13): 6 = 145.89 (q), 141.82 (4). 135.29 (q), 135.09 (q), 130.27, 129.85 [i-C], 128.04 [m-C], 127.70, 126.21, 126.01, 125.49, 122.84, 122.58 [p-C], 120.67 [o-C], 119.31 (q), 118.64, 108.70, 67.63; the signals of 2 CH groups and 2 quaternary C atoms were not ob- served. - MS: rnlz (%) = 362 ( 5 ) [M+], 270 (30), 169 (19), 140 (21), 115 (35), 93 (100). - CZ4Hl8N4 (362.4): calcd. C 79.54, H 5.01, N 15.46; found C 79.60, H 4.87, N 15.22.

6-[ (4-Fluorophenyl) amino]-1 4,14a-dihydroquinazolino[3,4-a]- perimidine (4b): Yield 0.18 g (470/0), colorless prisms, m.p.

Liebigs Ann. Chem. 1994, 745-749

Preparation of Quinazolino[3,4-a]perimidine Derivatives 747

208-209°C. - IR: 0 = 3381 cm-I, 1633. - 'H NMR (CDCI3): 6 = 7.69 (d, l H , 3J = 8.3 Hz), 7.49-7.16 (m, IOH), 7.07-6.88 (m. 3H), 6.65 (t, l H , 3J = 4.2 Hz), 5.86 (d, lH , 3J = 1.4 Hz), 4.53 (s,

(YO) = 303 (41) [M+], 270 (70), 169 (94), 168 (57), 140 (76), 139 (23), 115 (100). - CI8Hl3N3S (303.4): calcd. C 71.26, H 4.32, N 13.85; found C 71.32, H 4.16, N 13.69.

lH , NH). - 13C NMR (CDC13): 6 = 158.69 ( J F = 241.6, p-C), 146.13 (q), 141.72 (9). 135.22 (q), 134.94 (q), 130.23, 127.65, 126.13, 125.41, 122.54 (0-C and CH), 119.18 (i-C and q), 118.58, 115.28 (J = 22.3, m-C), 108.62, 67.57; the signals of 2 CH groups and 2 quaternary carbon atoms were not observed. - MS: rnlz (YO) = 380 (11) [M+], 270 (54), 169 (41), 168 (36), 140 (SO), 115 (100). - C24H17FN4 (380.4): calcd. C 75.77, H 4.50, N 14.73; found C 75.90, H 4.36, N 14.93.

6-[ (4- Methoxyphenyl) amino]-1 4,14a-dihydroquinazolino[3,4-a]- perimidine (4c): Yield 0.18 g (47%), colorless prisms, m.p. 119-120°C. - IR: 0 = 3415 cm-I, 1618. - 'H NMR (CDCI3): 6 = 7.66 (d, lH , 3J = 8.1 Hz), 7.44-7.14 (m, lOH), 6.98 (t, lH , 3J=7.3Hz),6.75(d,2H,3J=8.8Hz),6.65(t,1H,3J=4.1H~), 5.83 (s, 1 H), 4.63 (s, 1 H, NH), 3.72 (s, 3H). - 13C NMR (CDC13): 6 = 155.65 (p-C), 146.33 (q), 141.70 (q), 135.13 (q), 134.94 (q), 132.70 (q), 132.50 (q), 130.13, 127.56, 126.10, 125.82, 125.35, 122.70 (0-C), 122.28, 119.12 (q), 119.05 (i-C), 118.45, 113.96 (m- C), 108.61, 67.59, 55.42; the signals of 2 CH groups were not ob- served. - MS: mlz (%) = 392 (12) [M+], 270 (loo), 196 (26), 169 (22), 115 (17), 108 (15). - C ~ S H ~ ~ N ~ O (392.5): calcd. C 76.51, H 5.14, N 14.28; found C 76.39, H 5.30, N 14.17.

6-[ (4-Methylphenyl)amino]-14,14a-dihydroquinazolino[3,4-a]- perimidine (4d): Yield 0.19 g (51Y0), colorless prisms, m.p. 164-165°C. - IR: 0 = 3364 cm-I, 1660. - 'H NMR (CDC13): 6 = 7.69 (d, 1 H, 3J = 8.3 Hz), 7.56-7.18 (m, 9H), 7.05-7.02 (m, 4H), 6.68 (t, 1 H, 3J = 4.2 Hz), 5.89 (d, 1 H, 3J = 1.2 Hz), 4.56 (s, lH, NH), 2.26 (s, 3H). - I3C NMR (CDCl3): 6 = 146.16 (9). 141.77 (q), 135.27, 134.04 (p-C), 135.01 (q), 132.63 (q), 130.33, 129.65 (i-C), 129.34 (m-C), 127.69, 126.20, 126.00, 125.49, 122.58, 120.97 (0-C), 119.31 (q), 118.71, 108.80, 67.79, 20.83; the signals of 1 CH group and 1 quaternary carbon atom were not observed. - MS: rnlz (YO) = 376 (5) [M+], 270 (26), 168 (9), 133 (loo), 132 (46), 105 (21). - C25H2~N4 (376.5): calcd. C 79.76, H 5.35, N 14.88; found C 79.89, H 5.57, N 14.68.

14,14a-Dihydroquinazolino[3,4-a]perimidin-6(5H)-one and -thione (5 and 6): A mixture of iminophosphorane 2 (0.52 g, 1 mmol), anhydrous toluene (20 ml) and an excess of carbon dioxide or car- bon disulfide was heated in a sealed tube at 100°C for 20 h. After cooling, the separated solid was collected by filtration and recrys- tallized from toluene to give 5 or 6.

5: Yield 0.21 g (75%), yellow prisms, m.p. 268-269°C. - IR: 0 = 3358 cm-I, 1692. - 'H NMR (CDC13/[D6]DMSO): 6 = 5.91 (s, 1 H), 6.22 (s, 1 H, NH), 6.74 (t, 1 H, 3J = 4.2 Hz), 6.96 (d, 1 H, 3 J = 8.3 Hz), 6.99 (t, lH , 3J = 7.5 Hz), 7.24 (d, 2H, 3J = 4.1 Hz), 7.30-7.60 (m, SH), 9.79 (s, lH, NH). - I3C NMR (CDC13/

133.32 (q), 128.68, 126.00, 125.34, 124.24, 122.76, 120.53, 118.22, 117.21 (q), 116.71, 115.39 (q), 113.46, 106.53, 66.77. - MS: mlz (%) = 287 (58) [M+], 286 (52), 169 (loo), 168 (57), 140 (56), 129 (30), 115 (62). - CI8Hl3N30 (287.3): calcd. C 75.25, H 4.56, N 14.62; found C 75.41, H 4.30, N 14.90.

6: Yield 0.20 g (67%), yellow prisms, m.p. 251-252°C. - IR: F = 3228 cm-I, 1630. - 'H NMR ([D6]DMSO): 6 = 11.43 (s, 1 H, NH), 7.69 (dd, 2H, 3J = 8.3 Hz, 4J = 4.1 Hz), 7.47-7.37 (m, 3H), 7.31 (d, 2H, 3J = 4.2 Hz), 7.17 (d, 2H, 3J = 8.0 Hz), 7.03 (s, lH , NH), 6.74 (t, lH , 3J = 3.9 Hz), 6.07 (s, 1H). - I3C NMR ([D,]DMSO): 6 = 175.96 (q), 142.35 (q), 136.60 (q), 134.04 (q),

[DslDMSO): 6 = 150.03 (q), 141.27 (q), 135.31 (q), 133.50 (q),

133.72 (q), 130.15, 127.76, 126.57, 124.93, 124.40, 123.20, 121.95, 118.54 (q), 117.27, 117.09 (q), 114.01, 107.52, 67.07. - MS: rnlz

6-Arylquinazolino[3,4a]perimidines 7. - General Procedure: To a solution of iminophosphorane 3 (0.52 g, 1 mmol) in anhydrous toluene (20 ml) were added dropwise the appropriate aroyl chloride (1 mmol) and triethylamine (1.01 g, 1 mmol). The mixture was heated in a sealed tube at 160°C for 20 h. After cooling, the formed ammonium salt was separated by filtration, and the filtrate was concentrated to dryness. The residual material was chromato- graphed on silica gel (70-230 mesh; column 40 X 3.5 an) using EtOAchexane (1 :2) as eluent to give 7. 6-Phenylquinazolino[3,4-a]perimidine (7a): Yield 0.19 g (57%),

orange prisms, m.p. 182-183°C. - IR: 0 = 1619 cm-I, 1574. - 'H NMR (CDC13): 6 = 8.40 (d, 1 H, 3J = 7.8 Hz), 7.63-7.60 (m, 2H), 7.53 (dd, 2H, 3J = 7.6 Hz, 4J = 1.4 Hz), 7.45-7.27 (m, 6H), 7.20 (dd, 2H, 3J = 6.9 Hz, 4J = 1.3 Hz), 6.82 (t, lH , 3J = 7.9 Hz), 5.95 (d, 1 H, 3J = 7.7 Hz). - I3C NMR (CDCl3): 6 = 151.00 (9). 147.87 (q), 144.10 (q), 140.54 (q), 134.95 (i-C), 134.29 (q), 133.38 (q), 133.02, 130.17, 128.72 (OX), 128.54 (m-C), 128.42, 127.50, 126.94, 125.57 (2 CH), 123.31 (q), 122.56, 121.80 (q), 121.21, 117.58, 115.58. - MS: rnlz (%) = 345 (34) [M+], 216 (68), 215 (54), 214 (loo), 213 (12), 173 (38), 172 (54). - C24H15N3 (345.4): calcd. C 83.46, H 4.38, N 12.17; found C 83.30, H 4.12, N 12.31.

6-(4-Methylphenyl)quinazolino[3,4-a]perimidine (7b): Yield 0.14 g (40%), orange prisms, m.p. 206-207°C. - IR: 0 = 1618 cm-',

7.66-7.62 (m, 2H), 7.46-7.24 (m, 7H), 7.14 (d, 2H, 3J = 8.0 Hz), 6.87 (t, lH , 3J = 7.9 Hz), 6.03 (d, lH , 3J = 7.7 Hz), 2.36 (s, 3H, CH3). - I3C NMR (CDCl3): 6 = 151.02 (q), 148.18 (q), 144.19 (9). 140.59 (q), 140.24 (p-C), 134.24 (q), 133.39 (q), 133.15, 131.91

1572. - 'H NMR (CDC13): 6 = 8.46 (d, lH , 3J = 7.8 Hz),

(i-C), 129.23* (0-C), 128.71* (m-C), 128.39, 127.41, 126.88, 125.65 (2CH), 123.28(q), 122.54, 121.42(q), 121.24, 117.39, 115.73,21.44 (CH3); * assignments exchangeable. - MS: mlz (%) = 359 (93) [M+], 358 (36), 214 (32), 172 (93), 119 (loo), 91 (58), 90 (30), 89 (32). - C25H17N3 (359.4): calcd. C 83.54, H 4.77, N 11.69; found C 83.62, H 4.59, N 11.49.

6-(4-Methoxyphenyl)quinazolino[3,4-a]perimidine (7c): Yield 0.19 g (53%), yellow prisms, m.p. 215-216°C. - IR: 0 = 1625 cm-', 1608. - 'H NMR (CDC13): 6 = 8.41 (dd, 1 H, 3J = 7.8 Hz, 4J = 1.5 Hz), 7.63-7.60 (m, 2H), 7.49 (d, 2H, 3J = 9.0 Hz), 7.41 (t, 2H, 3J = 7.8 Hz), 7.34-7.16 (m, 3H), 6.90 (t, lH , 3J = 9.0 Hz), 6.85 (d, 2H, 3J = 9.0 Hz), 6.05 (d, lH, 3J = 7.5 Hz), 3.85 (s,

(q), 144.30 (q), 140.70 (q), 134.33 (q), 133.69 (q), 133.10, 130.54 (0-C), 128.48, 127.26, 127.04 (i-C), 126.81, 125.79, 125.60, 123.41 (q), 122.47, 121.72(q), 121.23, 117.54, 115.79, 113.97 (m-C), 55.44. - MS: rnlz (%) = 375 (100) [M+], 374 (44), 331 (26), 241 (31), 165 (20). - C25H17N30 (375.4): calcd. C 79.98, H 4.56, N 11.19; found C 80.12, H 4.70, N 11.35.

6-[Alkyl(aryl)amino]quinazolino[3,4-a]perimidines (8). - Gen- eral Procedure: To a solution of the iminophosphorane 3 (0.52 g, 1 mmol) in anhydrous CH2C12 (10 ml) was added the appropriate isocyanate (1 mmol). The resultant solution was stirred at room temp. for 20 h. Then, the solvent was removed under reduced press- ure, and the residue was chromatographed on silica gel (70-230 mesh; column 40 X 3.5 cm) using EtOAchexane (1 :2) as eluent to give 8.

6-(Phenylamino) quinazolino[3,4-a]perimidine (8a): Yield 0.28 g (79%), orange prisms, m.p. 211-212°C. - IR: 0 = 3330 cm-I,

3H). - I3C NMR (CDC13): 6 = 161.20 (p-C), 150.84 (q), 148.19

1624. - 'H NMR (CDC13): 6 = 8.27 (dd, 1 H, 3J = 8.1 Hz, 4J =

Liebigs Ann. Chem. 1994, 745-749

748 P. Molina, A. Alias, A. Balado, A. Arques

1.5 Hz), 7.62-7.19 (m, 11H), 7.16-7.00 (m, 4H). - I3C NMR (CDCI,): 6 = 148.33 (q), 144.89 (q), 142.71 (q), 140.47 (q), 137.97 (i-C), 134.96 (q), 133.10, 132.65 (q), 129.14, 126.50, 125.67, 124.82, 124.27, 123.75 (m-C and p-C), 123.75 (q), 123.23, 121.23, 120.19 (0-C), 120.06 (9). 117.88, 111.59. - MS: rnlz ("h) = 360 (15) [M+],

calcd. C 79.98, H 4.47, N 15.54; found C 79.85, H 4.31, N 15.78.

269(48), 166(15), 142(13), 140 (15), 113 (10). - C20H1&(312.4): calcd. C 76.90, H 5.16, N 17.94; found C 77.05, H 5.23, N 17.76.

6-(Isopropylamino)quinazolino[3,4-a]perimidine (8g): Yield 0.21 g (65%), yellow prisms, m.p. 132-133°C. - IR: 2 = 3415 cm-I,

1.5 Hz), 7.47 (td, 1 H, 3J = 9.0 Hz, 4J = 1.2 Hz), 7.36 (d, 2H, 3J = 140 (21), 114 (ll), 113 (16), 91 (8), 77 (100). - C24H16N4 (360.4): 1627. - 'H NMR (CDC13): 6 = 8.25 (dd, l H , 3J = 7.8 Hz, 4J =

6-[(4-Fluorophenyl)amino]quinazolino[3,4-a]perimidine (8b): Yield 0.25 g (70%), yellow prisms, m.p. 88-89°C. - IR: 2 = 3425 cm-I, 1625. - 'H NMR (CDCl,): 6 = 8.25 (d, l H , 3J = 7.8 Hz), 7.57-7.02 (m, 14H). - I3C NMR (CDC13): 6 = 159.12 ('JF =

(q), 133.05, 133.79 (i-C), 135.55 (q), 128.99, 126.38, 125.51, 124.65, 124.15, 123.62 (q), 123.16, 122.05 (3JF = 7.5, 0-C), 121.11, 119.95 (q), 117.77, 115.69 ( 2 J F = 22.0, m-C), 111.37. - MS: rnlz (YO) = 379 (30), 378 (100) [M+], 189 (38), 140 (23), 139 (ll), 95 (16). - C24H15FN4 (378.4): calcd. C 76.18, H 4.00, N 14.81; found C 76.27, H 4.23, N 14.67.

6-[(4-Methoxyphenyl)amino]quinazolino[3,4-a]perimidine (8c): Yield 0.25 g (65%), yellow prisms, m.p. 174-175°C. - IR: 2 = 3395 cm-', 1660. - 'H NMR (CDC13): 6 = 8.19 (dd, l H , 3J = 7.8 Hz, 4J = 1.2 Hz), 7.43-7.09 (m, 12H), 6.83 (d, 2H, 3J = 8.7 Hz), 3.75 (s, 3H, CH30). - 13C NMR (CDC13): 6 = 156.17 (p-C), 148.02 (q), 144.93 (q), 143.01 (q), 140.40 (q), 134.79 (q), 132.97, 132.72 (q), 130.09 (i-C), 128.85, 126.37, 125.47, 124.62, 123.71,

(m-C), 111.52,55.48 (CH30). - MS: mlz ("h) = 390 (56) [M+], 201

(390.4): calcd. C 76.91, H 4.65, N 14.35; found C 76.80, H 4.81, N 14.51.

6-[(4-Methylphenyl)amino]quinazolino[3,4-a]perimidine (8d): Yield 0.27 g (72%), orange prisms, m.p. 80-81°C. - IR: 2 = 3217 cm-', 1629. - 'H NMR (CDC13): 6 = 8.26 (d, l H , 3J = 7.8 Hz), 7.49-7.45 (m, 4H), 7.41 (d, 2H, 3J = 4.5 Hz), 7.36 (d, 2H, 3J = 6.0 Hz), 7.26-7.08 (m, 6H), 2.32 (s, 3H, CH3). - 13C NMR

(q), 134.98 (i-C), 133.49 (p-C), 133.08, 132.81 (q), 129.69 (m-C), 129.06, 126.51, 125.67, 124.77, 124.06, 123.81 (q), 123.16, 121.15, 120.51 (0-C), 120.09 (q), 117.80, 111.57, 20.91 (CH3). - MS: rnlz

(51), 106 (24), 91 (100). - C25H18N5 (374.4): calcd. C 80.19, H 4.85, N 14.96; found C 80.00, H 4.57, N 14.75. 6-[(4-Chlorophenyl)amino]quinazolino[3,4-a]perimidine (8e):

Yield 0.23 g (6O%), yellow prisms, m.p. 113-114°C. - IR: 2 = 3415 cm-', 1625. - 'H NMR (CDC13): 6 = 8.17 (d, 1 H, 3J = 7.5 Hz), 7.53 (d, 2H, = 8.9 Hz), 7.47-7.00 (m, lOH), 6.93 (d, 2H,

142.18 (q), 140.25 (q), 136.48 (i-C), 134.78 (q), 132.96, 132.40 (q), 130.00 (p-C), 128.90 (0-C and CH), 126.28, 125.47, 124.66, 124.22, 123.50(q), 123.09, 121.10(m-C), 121.07, 119.96(q), 117.68, 111.29. - MS: rnlz (%) = 396 (38) [M+ + 21, 394 (100) [M+], 270 (15), 149 (12). - C24H15C1N4 (394.9): calcd. C 73.00, H 3.83, N 14.19; found C 72.91, H 3.69, N 14.05.

6-(Ethylamino)quinazolino[3,4-a]perimidine (80: Yield 0.21 g (67%), yellow prisms, m.p. 123-124°C. - IR: 2 = 3409 cm-I,

(t, 2H, 3J = 7.6 Hz), 7.42-7.19 (m, 4H), 7.15-7.08 (m, 3H), 5.19 (br. s, 1 H, NH), 3.65-3.53 (m, 2H), 1.23 (t, 3H, 3J = 7.2 Hz). -

(q), 132.98, 132.88 (q), 128.90, 126.21, 125.60, 123.96, 123.71 (q),

14.50 (CH,). - MS: rnlz (YO) = 312 (100) [M+], 311 (51), 270 (24),

241.8, p-C), 148.10 (q), 144.74 (q), 142.73 (q), 140.32 (q), 134.85

123.57 (q), 122.92, 122.47 (0-C), 121.07, 119.93 (q), 117.54, 114.32

(loo), 183 (82), 173 (16), 140 (30), 139 (27), 108 (41). - C25H18N40

(CDCI3): 6 = 148.39 (q), 145.05 (q), 142.83 (4, 140.55 (q), 135.26

c / o ) = 374 (13) [M+], 187 (41), 149 (31), 140 (62), 133 (21), 113

3J = 7.5 Hz). - 13C NMR (CDC13): 6 = 147.93 (q), 144.55 (q),

1621. - 'H NMR (CDC13): 6 = 8.22 (d, l H , 3J = 7.9 Hz), 7.47

13C NMR (CDC13): 6 = 148.54 (q), 145.82 (2 q), 140.70 (4, 134.98

122.93, 122.74, 120.66, 119.12 (q), 117.35, 111.09, 36.70 (CH,),

8.1 Hz), 7.34-7.26 (rn, 3H), 7.20-7.10 (m, 3H), 5.07 (d, l H , 3J = 7.0 Hz, NH), 4.50-4.44 (m, lH), 1.29 (d, 6H, 3J = 6.5 Hz).

(9). 135.10 (q), 133.16, 132.95 (9). 129.07, 126.34, 125.69, 124.07, 123.83 (q), 122.99, 122.88, 120.79, 119.04 (q), 117.44, 111.22,43.71, 22.79. - MS: rnlz (Oh) = 326 (100) [M+], 270 (19), 269 (55), 166 (41), 140 (29). - C2'HI8N4 (326.4): calcd. C 77.28, H 5.56, N 17.16; found C 77.13, H 5.74, N 17.04.

- I3C NMR (CDCl3): 6 = 148.79 (q), 146.00 (q), 145.16 (9). 140.78

6-(n-Propylamino)quinazolino[3,4-a]perimidine (8h): Yield 0.14 g (43%), oil. - IR: 2 = 3364 cm-I, 1630. - 'H NMR (CDC13): 6 = 8.23 (dd, l H , 3J = 7.8 Hz, 3J = 1.2 Hz), 7.48 (td, l H , 3J = 7.2 Hz, 4J = 1.2 Hz), 7.41-7.35 (rn, 2H), 7.30-7.21 (m, 3H), 7.16-7.09 (m, 3H), 5.21 (t, l H , 3J = 4.2 Hz, NH), 3.52 (m, 2H), 1.68 (qt, 2H, 3J = 7.5 Hz, ' J = 6.9 Hz), 1.01 (t, 3H, 3J = 7.5 Hz). - I3C NMR (CDCl3): 6 = 148.69 (q), 146.01 (q), 145.96 (4, 140.81 (q), 135.05 (q), 133.09, 132.98 (q), 129.02, 126.29, 125.64, 124.06, 123.80 (q), 122.99, 122.83, 120.73, 119.18 (9). 1 17.40, 1 1 1.12,43.64, 22.46, 11.80. - MS: mlz (%) = 326 (23) [M+], 282 (33), 269 (l l) , 166 (54), 163 (26), 140 (100). - CZ1H18N4 (326.4): calcd. C 77.28, H 5.56, N 17.16; found C 77.00, H 5.35, N 17.31.

Quinazolino[3,4-a]perimidine-6(5H)-one and -thione (9 and 10). - General Procedure: These compounds were prepared from irni- nophosphorane 3 by using the same method as described for the preparation of compounds 5 and 6.

9: Yield 0.25 g (go%), yellow prisms, m.p. 336-337°C. - IR: 2 = 3392 cm-I, 1706. - 'H NMR ([D,]DMSO): 6 = 11.15 (br. s, l H , NH), 8.17 (d, l H , ' J = 7.8 Hz), 8.12 (d, lH , 3J = 8.0 Hz), 7.56-7.26 (m, 5H), 7.14 (t, l H , 3J = 7.7 Hz), 7.04 (d, l H , 3J = 8.1 Hz), 6.95 (dt, l H , ' J = 6.1 Hz, 4J = 1.8 Hz). - I3C NMR ([D,]DMSO): 6 = 148.52 (q), 147.18 (q), 139.57 (q), 137.81 (q), 134.19 (q), 133.59, 128.10, 127.32, 126.47, 122.92, 122.46, 122.21, 122.05 (q), 117.16, 115.46 (q), 114.66, 114.16; the signal of 1 quat- ernary C atom was not observed. - MS: rnlz (YO) = 285 (100) [M+], 143 (49), 140 (54), 139 (52), 121 (55), 115 (36), 114 (59), 113 (51). - CI8Hl1N30 (285.3): calcd. C 75.78, H 3.89, N 14.73; found C 75.88, H 3.75, N 14.53.

10: Yield 0.28 g (85Y0), yellow prisms, m.p. 270-271°C. - IR: 2 = 3347 cm-', 1628. - 'H NMR ([D,]DMSO): 6 = 12.68 (s, 1 H, NH), 8.27 (d, l H , ' J = 7.7 Hz), 8.02 (d, l H , 3J = 7.9 Hz), 7.64-7.37 (m, 5H), 7.32-7.23 (m, 2H), 7.15 (d, l H , 3J = 7.1 Hz).

136.39 (q), 133.49, 133.05 (q), 132.20 (q), 127.49, 125.71, 125.61, 124.61, 123.09, 122.72, 122.54 (q), 119.67, 118.15, 117.87 (q), 115.10. - MS: rnlz (YO) = 301 (4) [M+], 150 (39), 140 (48), 139

calcd. C 71.74, H 3.68, N 13.94; found C 71.89, H 3.54, N 13.76.

- I3C NMR ([D,]DMsO): 6 = 172.85 (q), 144.74 (q), 137.83 (q),

(36), 113 (59), 102 (58), 88 (47), 75 (100). - C18HllN3S (331.4):

1'1 [la] J. H. Richmond, Six-membered Heterocyclic Nitrogen Com- pounds with Three Condensed Rings, Academic Press, New York, 1958, p. 518. - [Ib] A. F. Pozharskii, V. V. Dal'nikovskaya, Russ. Chem. Rev. (Engl. Transl.) 1981, 50, 816. - [Ic] J. Elguero, R. M. Claramunt, A. Fruchier, Spectroscopy (Ottawa) 1988, 6, 295. - [Id] C. Foces-Foces, A. L. Llamas-Saiz, R. M. Clara- munt, D. Sanz, J. Dotor, J. Elguero, .I Crystallogr. Spectrosc.

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