One-Pot Three-Component Synthesis
of 4(3H)-Quinazolinones from Benzyl Halides,
Isatoic Anhydride, and Primary Amines

Mehdi Adib; Ehsan Sheikhi; Hamid Reza Bijanzadeh

doi:10.1055/s-0031-1290098

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Synlett 2012(1): 85-88
DOI: 10.1055/s-0031-1290098

LETTER

One-Pot Three-Component Synthesis of 4(3H)-Quinazolinones from Benzyl Halides, Isatoic Anhydride, and Primary Amines

Mehdi Adib*^a, Ehsan Sheikhi^a, Hamid Reza Bijanzadeh^b
^a School of Chemistry, University College of Science, University of Tehran, P. O. Box 14155-6455, Tehran, Iran
Fax: +98(21)66495291; e-Mail: madib@khayam.ut.ac.ir;
^b Department of Chemistry, Tarbiat Modares University, P. O. Box 14115-175, Tehran, Iran

Further Information

Publication History

Received 7 August 2011
Publication Date:
07 December 2011 (online)

Abstract
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Abstract

A novel, one-pot, and three-component synthesis of 4(3H)-quinazolinones is described. Benzyl halides are oxidized to aldehydes under mild Kornblum conditions then undergo a three-component reaction with isatoic anhydride and primary amines to produce 4(3H)-quinazolinones in excellent yields.

Key words

benzyl halides - Kornblum oxidation - isatoic anhydride - amines - 4(3H)-quinazolinones - multicomponent reactions

References and Notes

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27

Typical Procedure for the Preparation of Compounds 4a-m, Exemplified with 4a (Table 1, Entry 1)
A mixture of benzyl chloride (0.126 g, 1 mmol) and K₂CO₃ (1.5 mmol) in DMSO (1 mL) was stirred for 4 h at 90 ˚C. Then, isatoic anhydride (0.163 g, 1 mmol) and aniline (0.093 g, 1 mmol) were added to the reaction mixture and stirring continued at 90 ˚C for 2 h. The reaction mixture was cooled to r.t., H₂O (3 mL) was added, and stirring was continued for 1 h at ambient temperature. The white precipitate was filtered, washed with H₂O (2 × 2 mL), dried, and then recrystallized from of n-hexane-EtOAc (3:1) to give 4a as white solid.
2,3-Diphenylquinazolin-4 (3 H )-one (4a, Table 1, Entry 1)
Yield 0.286 g (96%); white solid. ^¹H NMR (500.1 MHz, CDCl₃): δ = 7.12-7.35 (m, 10 H, 10 × CH), 7.53 (d, J = 7.8 Hz, 1 H, CH), 7.80 (d, J = 7.5 Hz, 2 H, 2 × CH), 8.33 (d, J = 8.0 Hz, 1 H, CH). ^¹³C NMR (125.8 MHz, CDCl₃): δ = 121.0, 127.4, 127.8, 128.0, 128.2, 128.5, 128.7, 129.4, 129.5, 129.6, 135.0, 135.9, 138.2, 147.7, 155.2, 162.5.
3-(4-Methoxyphenyl)-2-phenylquinazolin-4 (3 H )-one (4c, Table 1, Entry 3)
Yield 0.312 g (95%); white solid. ^¹H NMR (500.1 MHz, CDCl₃): δ = 3.75 (s, 3 H, OCH₃), 6.77 (d, J = 8.2 Hz, 2 H, 2 × CH), 6.99 (d, J = 8.2 Hz, 2 H, 2 × CH), 7.15-7.23 (m, 3 H, 3 × CH), 7.35 (d, J = 7.7 Hz, 2 H, 2 × CH), 7.47 (d, J = 7.8 Hz, 1 H, CH), 7.73-7.77 (m, 2 H, 2 × CH), 8.33 (d, J = 8.0 Hz, 1 H, CH). ^¹³C NMR (125.8 MHz, CDCl₃): δ = 55.3, 114.4, 121.0, 127.1, 127.4, 128.2, 128.8, 129.2, 129.6, 130.3, 130.5, 135.2, 136.3, 147.7, 155.5, 159.8, 162.7. 3-(4-Methoxybenzyl)-2-phenylquinazolin-4 (3 H )-one (4f, Table 1, Entry 6)
Yield 0.308 g (90%); white solid. ^¹H NMR (500.1 MHz, CDCl₃): δ = 3.79 (s, 3 H, OCH₃), 5.20 (s, 2 H, CH₂), 6.75 (d, J = 8.1 Hz, 2 H, 2 × CH), 6.84 (d, J = 8.1 Hz, 2 H, 2 × CH), 7.33-7.56 (m, 6 H, 6 × CH), 7.76 (d, J = 7.7 Hz, 2 H, 2 × CH), 8.35 (d, J = 7.9 Hz, 1 H, CH). ^¹³C NMR (125.8 MHz, CDCl₃): δ = 48.7, 55.0, 113.2, 121.0, 127.0, 127.1, 127.7, 127.9, 128.4, 128.5, 128.7, 129.9, 134.0, 135.2, 147.0, 156.5, 158.8, 162.7. 2-Phenyl-3-phenylethylquinazolin-4 (3 H )-one (4g, Table 1, Entry 7)
Yield 0.300 g (92%); white solid. ^¹H NMR (500.1 MHz, CDCl₃): δ = 3.41 (t, J = 7.7 Hz, 2 H, CH₂), 4.68 (t, J = 7.7 Hz, 2 H, CH₂), 7.37-7.60 (m, 10 H, 10 × CH), 7.66 (d, J = 7.9 Hz, 1 H, CH), 7.95 (d, J = 7.6 Hz, 2 H, 2 × CH), 8.44 (d, J = 7.9 Hz, 1 H, CH). ^¹³C NMR (125.8 MHz, CDCl₃): δ = 33.9, 46.8, 120.1, 126.6, 126.7, 127.1, 127.3, 127.6, 127.9, 128.4, 128.7, 130.0, 134.1, 135.3, 138.3, 147.0, 156.5, 162.3.
2-(4-Chlorophenyl)-3-phenylquinazoline-4 (3 H )-one (4j, Table 1, Entry 10)
Yield 0.312 g (94%); white solid. ^¹H NMR (500.1 MHz, CDCl₃): δ = 7.12-7.21 (m, 4 H, 4 × CH), 7.26-7.33 (m, 5 H, 5 × CH), 7.52 (d, J = 7.9 Hz, 1 H, CH), 7.79 (d, J = 8.3 Hz, 2 H, 2 × CH), 8.34 (d, J = 8.1 Hz, 1 H, CH). ^¹³C NMR (125.8 MHz, CDCl₃): δ = 121.1, 127.1, 127.4, 127.8, 128.1, 128.7, 129.3, 129.5, 130.6, 133.7, 134.9, 135.6, 137.2, 147.1, 154.8, 162.6. 2-(4-Chlorophenyl)-3-(4-methoxybenzyl)quinazolin-4 (3 H )-one (4k, Table 1, Entry 11)
Yield 0.361 g (96%); white solid. ^¹H NMR (500.1 MHz, CDCl₃): δ = 3.79 (s, 3 H, CH₃), 5.22 (s, 2 H, CH₂), 6.77 (d, J = 8.2 Hz, 2 H, 2 × CH), 6.82 (d, J = 8.4 Hz, 2 H, 2 × CH), 7.33 (d, J = 8.2 Hz, 2 H, 2 × CH), 7.43 (d, J = 8.4 Hz, 2 H, 2 × CH), 7.49-7.53 (m, 1 H, CH), 7.70-7.81 (m, 2 H, 2 × CH), 8.33 (d, J = 7.9 Hz, 1 H, CH). ^¹³C NMR (125.8 MHz, CDCl₃): δ = 48.7, 55.1, 113.6, 121.1, 127.0, 127.2, 127.6, 128.1, 128.4, 128.8, 129.3, 133.9, 134.4, 136.2, 147.5, 155.7, 158.2, 162.5.
3-(4-Methylphenyl)-2-(4-nitrophenyl)quinazolin-4 (3 H )-one (4m, Table 1, Entry 13)
Yield 0.328 g (92%); pale yellow solid. ^¹H NMR (500.1 MHz, CDCl₃): δ = 2.29 (s, 3 H, CH₃), 7.00 (d, J = 8.3 Hz, 2 H, 2 × CH), 7.17 (d, J = 8.3 Hz, 2 H, 2 × CH), 7.51-7.62 (m, 3 H, 3 × CH), 7.90 (d, J = 8.2 Hz, 2 H, 2 × CH), 8.12 (d, J = 8.2 Hz, 2 H, 2 × CH), 8.34 (d, J = 7.9 Hz, 1 H, CH). ^¹³C NMR (125.8 MHz, CDCl₃): δ = 22.3, 121.7, 123.4, 127.2, 127.7, 127.9, 128.7, 129.9, 130.2, 134.4, 134.8, 139.3, 141.6, 147.4, 147.6, 153.2, 161.6.