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Synlett 2003(2): 0256-0258
DOI: 10.1055/s-2003-36780
LETTER
© Georg Thieme Verlag Stuttgart · New York

An Efficient Route to Novel 2-(Salicylmethylidine)imidazolidines and (Salicylmethylidene)hexahydropyrimidines through Reactions of 2-(N-Methylanilino)-3-formylchromone with Aliphatic Diamines

Gurmit Singh, Gurpinder Singh, M. P. S. Ishar*
Department of Pharmaceutical Sciences, Guru Nanak Dev University, Amritsar - 143005, Punjab, India
Fax: +91(183)258820; e-Mail: mpsishar@rediffmail.com;
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Publication History

Received 23 November 2002
Publication Date:
22 January 2003 (online)

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Abstract

Contrary to the reactions of 2-(N-methylanilino)-3-formylchromones (3) with aliphatic/aromatic primary amines, including o-phenylenediamine, which involve nucleophilic substitution at C2 and/or condensation with the 3-formyl function, the reactions of 3 with aliphatic diamines such as ethylenediamine and 1,3-diaminopropane proceed through sequential attack by both amino functions at C2 in 3. The latter reactions afford, through nucleophilic substitution of the N-methylanilino moiety followed by chromone ring opening, novel potentially biologically active, 2-(formyl-salicyl-methylidene)imidazolidines (7a-c) and 2-(formyl-salicyl-methylidene)hexahydropyrimidines (7d-f) in high yields.

Key words

imidazolidines - hexahydropyrimidines - chromones - nucleophilic substitution - diamines

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    2-(Formyl-salicyl-methylidene)imidazolidine (7a): Colorless crystalline solid, mp 265-266 °C (acetone). UV (MeOH): 362.4, 263, 228.4 nm. IR (KBr): 3310 (s), 3118 (b), 1672 (HC=O), 1625 (C=O), 1602, 1533, 1452, 1434
    cm-1. 1H NMR (200 MHz, DMSO-d 6): δ = 9.18 (overlapping singlets, 2 H, NH, OH), 8.94 (s, 1 H, HC=O), 8.30 (s, 1 H, NH), 7.22 (dt, 1 H, J = 8.61, 2.35 Hz, C4′-H), 7.03 (dd, 1 H, J = 8.29 Hz, 1.69, C6′-H), 6.80-6.76 (m, 2 H, C3′-H and C5′-H), 3.63 (s, 4 H, N-CH2 × 2). MS: m/z (%) = 230 (1) [M+ - 2], 214 (1.5), 213 (3), 205 (5), 204 (29), 203 (8), 84 (100), (Found: C, 62.28; H, 5.11; N, 12.34. C12H12N2O3 requires C, 62.06; H, 5.21; N 12.06 %).
    2-[(5-Chlorosalicyl)-formyl-methylidene]imidazolidine (7b): Colorless crystalline solid, mp 271-272 °C (acetone). UV (MeOH): 262, 223 nm. IR (KBr): 3350 (b), 3100 (b), 1668 (HC=O), 1619 (C=O), 1595, 1556, 1532, 1541 cm-1. 1H NMR (300 MHz, DMSO-d 6): δ = 9.75 (br s, 1 H, OH), 9.21 (br s, 2 H, NH × 2), 9.10 (s, 1 H, CHO), 7.15 (dd, 1 H, J = 8.61, 2.35 Hz, C4′-H), 7.08 (d, 1 H, J = 2.30 Hz, C6′-H), 6.85 (d, 1 H, J = 8.69 Hz, C3′-H), 3.77 (s, 4 H, N-CH2 × 2). 13C NMR (75 MHz, DMSO-d 6): δ = 190.43 (C=O), 188.06 (CHO), 163.43 (C2), 152.69 (C2), 129.72 (C1′), 129.31 (CH), 127.67 (CH), 122.59 (C5′), 117.25 (CH), 99.65 (quat.), 42.43 (N-CH2). Mass (FAB+): m/z (%) = 269 (31) [(M + H)+ + 2 (37Cl)], 268 (22) [(M + H)+ + 1], 267 (100) [(M + H)+ for 35Cl], 266 (36), 249 (37), 155 (18), 154 (93), 140 (30), 139 (24), 138 (45), 137 (68), (Found: C, 53.87; H, 4.01; N, 10.81. C12H11N2O3Cl requires C, 54.05; H, 4.16; N 10.50%].
    2-[Formyl-(5-Methylsalicyl)-methylidene]imidazolidine (7c): Colorless crystalline solid, mp 267-269 °C (acetone). UV (CHCl3): 324, 287, 267.5, 256 nm. IR (KBr): 3290 (b), 3060 (b), 1660 (HC=O), 1622 (C=O), 1580, 1520, 1500, 1428, 1392, 1378, 1331, 1288, 1261 cm-1. 1H NMR (200 MHz, CDCl3-DMSO-d 6, 8:2): δ = 9.75 (br s, 1 H, -OH), 9.33 (s, 1 H, CHO), 9.24 (br s, 2 H, NH × 2), 7.10-7.06 (m, 2 H, arom.-Hs), 6.80 (d, 1 H, J = 8.09 Hz, C3′-H), 3.82 (s, 4 H, N-CH2 × 2), 2.26 (s, 3 H, Ar-CH3). MS: m/z (%) = 245 (8) [M+ - 1], 243 (9), 188 (11), 169 (100), 111 (60), 94 (41), 83 (47), 71 (78), (Found: C, 63.18; H, 5.51; N, 11.64. C13H14N2O3 requires C, 63.40; H, 5.73; N 11.38%).
    2-(Formyl-salicyl-methylidene)hexahydropyrimidine (7d): Colorless crystalline solid (219 mg, 89%), mp 176-177 °C (acetone). UV (MeOH): 332, 262.5, 219 nm. IR (KBr): 3400 (b), 3090 (b), 2755, 1656 (HC=O), 1642 (C=O), 1604, 1572, 1401, 1365, 1338, 1326, 1302, 1273, 1245, 1224, 1147 cm-1: 1H NMR (200 MHz, DMSO-d 6): δ = 10.64 (br s, 2 H, NH and OH), 9.83 (br s, 1 H, NH), 9.13 (s, 1 H, CHO), 7.37 (dt, 1 H, J = 7.02, 1.51 Hz, C4′-H), 7.24 (br d, 1 H, J = 6.42 Hz, C6′-H), 7.07-6.99 (m, 2 H, C5′-H and C3′-H), 3.61 (b, 4 H, N-CH2 × 2), 2.13-2.08 (m, 2 H, -CH2). 13C NMR (50 MHz, DMSO-d 6): δ = 194.25 (C=O), 189.70 (CHO), 158.82 (C2), 153.70 (C2′), 130.10 (CH), 128.98 (C1′), 128.80 (CH), 119.25 (CH), 115.80 (CH), 100.51 (quat.), 37.78 (N-CH2), 19.06 (CH2). MS: m/z (%) = 246 (15) [M+], 228 (69) [M+ - 18], 172 (42), 108 (100), (Found: C, 63.26; H, 5.48; N, 11.11. C13H14N2O3 requires C, 63.40; H, 5.73; N 11.38%).
    2-[(5-Chlorosalicyl)-formyl-methylidene]hexahydro-pyrimidine (7e): Colorless crystalline solid, mp 169-171 °C (acetone). UV (CHCl3): 330, 269.5, 251 nm. IR (KBr): 3490 (b), 3100 (b), 1657 (HC=O), 1635 (C=O), 1611, 1535, 1468, 1430, 1418, 1358, 1322, 1282, 1260, 1240, 1215 cm-1. 1H NMR (200 MHz, CDCl3-DMSO-d 6, 8:2): δ = 10.46 (br, 2 H, NHs), 9.02 (s, 1 H, CHO), 7.28-7.01 (m, 2 H, arom.-Hs), 6.80 (d, 1 H, J = 8.58 Hz, C3′-H), 3.44-3.41 (m, 4 H, N-CH2 × 2), 2.00-1.93 (m, 2 H, -CH2). MS: m/z (%) = 282 [(M+ + 2 (37Cl)], 281 (1.9), 280 (10)[M+ (35Cl)], 279 (35), 264 (8), 262 (31), 254 (14), 252 (30), 247 (5), 246 (3), 245 (18), 152 (4), 150 (18), 172 (5), 171 (23), 169 (70), 99 (15), 98 (100), 97 (14), (Found: C, 55.84; H, 4.81; N, 9.63. C13H13N2O3Cl requires C, 55.62; H, 4.67; N, 9.98%).
    2-[Formyl-(5-methylsalicyl)-methylidene]hexahydro-pyrimidine (7f): Creamy yellow crystalline solid, mp 160-162 °C (acetone). UV (CHCl3): 332, 307, 271.5, 256.5 nm. IR (KBr): 3360 (b), 3040 (b), 1658 (HC=O), 1633 (C=O), 1606, 1571, 1470, 1451, 1390, 1361, 1280 cm-1. 1H NMR (200 MHz, CDCl3): δ = 10.51 (br, 2 H, NHs), 9.35 (s, 1 H, CHO), 7.14-7.08 (m, 2 H, arom -Hs), 6.84 (d, 1 H, J = 8.26 Hz, C3′-H), 3.48-3.41 (s, 4 H, N-CH2 × 2), 2.24 (s, 3 H, Ar-CH3), 2.05-1.97 (m, 2 H, CH2). 13C NMR (50 MHz, CDCl3): δ = 196.66 (C=O), 189.78 (CHO), 159.99 (C2), 156.83 (C2′), 133.41 (CH), 131.71 (CH), 127.11 (C1′), 122.16 (C5′), 117.11 (CH), 100.06 (quat.), 37.81 (N-CH2), 20.41 (Ar-CH3), 19.20 (CH2). MS: m/z (%) = 260 (20) [M+], 259 (18), 169 (91), 111 (76), 83 (49), 71 (100), (Found: C, 64.28; H, 5.96; N, 10.99. C14H16N2O3 requires C, 64.60; H, 6.20; N 10.76%).
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7

General Procedure for Reactions of 2-( N -Methyl-anilino)-3-formylchromones (3a-c) with Aliphatic Diamines (Ethylenediamine and 1,3-Diaminopropane): 2-(N-Methylanilino)-3-formylchromones (3a-c, 1.0 mmol) were dissolved in acetonitrile-water (80:20, 50 mL) at reflux and the solutions of diamines (1.0 mmol) in acetonitrile (5 mL) were added to the above solutions. The contents were heated at reflux for 2 h, after which the solvent was evaporated under vacuum. The crude products were directly crystallized and recrystallized from acetone.