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Synlett 2010(6): 921-923  
DOI: 10.1055/s-0029-1219562
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

An Efficient Three-Component Synthesis of 3-(1-Hydroxyalkyl)[1,2,4]-triazolo[4,3-c]quinazolines

Mehdi Adib*a, Samira Ansaria, Shahzad Feizia, Hamid Reza Bijanzadehb
a School of Chemistry, University College of Science, University of Tehran, PO Box 14155-6455, Tehran, Iran
Fax: +98(21)66495291; e-Mail: madib@khayam.ut.ac.ir;
b Department of Chemistry, Tarbiat Modarres University, PO Box 14115-175, Tehran, Iran
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Publication History

Received 10 November 2009
Publication Date:
02 March 2010 (online)

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Abstract

An efficient three-component synthesis of 3-(1-hydroxyalkyl)[1,2,4]triazolo[4,3-c]quinazolines is described. A mixture of N-isocyaniminotriphenylphosphorane, an aldehyde, and a 4(3H)-quinazolinone undergo a 1:1:1 addition reaction in refluxing THF to afford the title compounds in good to excellent yields.

Key words

N-isocyaniminotriphenylphosphorane - 4(3H)-quin­azolinones - aldehydes - 3-(1-hydroxyalkyl)[1,2,4]triazolo[4,3-c]quin­azolines - multicomponent reactions - cyclizations - heterocycles

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19

General Procedure for the Preparation of Compounds 4a-l
A mixture of N-isocyaniminotriphenylphosphorane (1 mmol) and the appropriate aldehyde (1 mmol) was dissolved in hot THF (5 mL). Then the appropriate 4 (3H)-quinazo-linone (1 mmol) was added to the reaction mixture which was refluxed for 3 h. Then, the solvent was removed under the reduced pressure, and the residue was purified by TLC using CHCl3-EtOAc (3:1) as eluent. The solvent was removed, and the product was obtained as colorless crystals.
3-[1-Hydroxy-1-(4-fluorophenyl)methyl]-5-phenyl-[1,2,4]triazolo[4,3- c ]quinazoline (4c)
Yield 0.34 g (93%); colorless crystals; mp 192-193 ˚C. IR (KBr): 3266 (OH), 1609, 1515, 1374, 1332, 1264, 1211, 1187, 1156, 1106, 1056, 1019, 947, 863, 794, 769, 680 cm-¹. ¹H NMR (500.1 MHz, DMSO-d 6): δ = 5.35 (br s, 1 H, CH), 6.02 (d, J = 4.6 Hz, 1 H, OH), 7.08 (dd, J = 8.8, 8.9 Hz, 2 H, 2 × CH), 7.11-7.19 (m, 2 H, 2 × CH), 7.56-7.66 (m, 4 H, 4 × CH), 7.78 (dd, J = 6.8, 7.4 Hz, 2 H, 2 × CH), 7.86 (dd, J = 7.3, 8.1 Hz, 1 H, CH), 7.96 (d, J = 8.1 Hz, 1 H, CH), 8.54 (d, J = 7.9 Hz, 1 H, CH). ¹³C NMR (125.8 MHz, DMSO-d 6): δ = 65.94 (CH), 114.46 (d, ² J FC = 21.4 Hz, CH), 115.94 (C), 122.56, 127.89, 128.28 and 128.73 (4 × CH), 128.87 (d, ³ J FC = 8.1 Hz, CH), 129.25, 130.63 and 131.83 (3 × CH), 133.48 (C), 137.16 (d, 4 J FC = 2.7 Hz, C), 140.33, 145.65, 148.88 and 150.75 (4 × C), 161.45 (d, ¹ J CF = 243.2 Hz, CF). MS (EI): m/z (%) = 370 (6) [M+], 279 (20), 247 (12), 205 (9), 167 (23), 149 (100), 113 (10), 104 (9), 83 (9), 71 (18), 57 (29). Anal. Calcd for C22H15FN4O (370.38): C, 71.34; H, 4.08; N, 15.13. Found: C, 71.3; H, 4.2; N, 15.1.
3-[1-Hydroxy-1-(4-nitrophenyl)methyl]-5-(4-methyl-phenyl)[1,2,4]triazolo[4,3- c ]quinazoline (4f)
Yield 0.40 g (97%); colorless crystals; mp 228 ˚C. IR (KBr): 3344 (OH), 1614, 1511, 1466, 1335, 1181, 1105, 1069, 1039, 986, 948, 818, 769, 696 cm-¹. ¹H NMR (500.1 MHz, DMSO-d 6): δ = 2.42 (s, 3 H, CH3), 5.52 (d, J = 5.8 Hz, 1 H, CH), 6.25 (d, J = 5.8 Hz, 1 H, OH), 7.37 (d, J = 7.2 Hz, 2 H, 2 × CH), 7.49 (d, J = 8.7 Hz, 2 H, 2 × CH), 7.73 (d, J = 7.8 Hz, 2 H, 2 × CH), 7.79 (dd, J = 7.4, 7.7 Hz, 1 H, CH), 7.88 (t, J = 7.1, 7.2 Hz, 1 H, CH), 7.98 (d, J = 8.1 Hz, 1 H, CH), 8.16 (d, J = 8.7 Hz, 2 H, 2 × CH), 8.53 (d, J = 7.4 Hz, 1 H, CH). ¹³C NMR (125.8 MHz, DMSO-d 6): δ = 21.12 (CH3), 65.77 (CH), 115.83 (C), 122.61, 122.92, 127.93, 127.96, 128.75, 128.85, 129.26 (7 × CH), 130.59 (C), 131.98 (CH), 140.48, 140.52, 145.81, 146.79, 148.70, 149.08 and 150.11 (7 × C). MS (EI): m/z (%) = 411 (2) [M+], 386 (5), 370 (14), 277 (100), 247 (31), 205 (24), 183 (19), 152 (16), 123 (12), 97 (18), 77 (28). Anal. Calcd for C23H17N5O3 (411.41): C, 67.15; H, 4.16; N, 17.02. Found: C, 67.2; H, 4.2; N, 16.9.