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Synlett 2014; 25(11): 1596-1600
DOI: 10.1055/s-0033-1341202
letter
© Georg Thieme Verlag Stuttgart · New York

An Efficient Approach to the Synthesis of Coumarin-Bearing 2,3-Dihydro-4(1H)-Quinazolinone Derivatives Using a Piperidine and Molecular Iodine Dual-Catalyst System

Abdolali Alizadeh*
a   Department of Chemistry, Tarbiat Modares University, P.O. Box 14115-175, Tehran, Iran   Fax: +98(21)88006544   Email: abdol_alizad@yahoo.com   Email: aalizadeh@modares.ac.ir
,
Rashid Ghanbaripour
a   Department of Chemistry, Tarbiat Modares University, P.O. Box 14115-175, Tehran, Iran   Fax: +98(21)88006544   Email: abdol_alizad@yahoo.com   Email: aalizadeh@modares.ac.ir
,
Long-Guan Zhu
b   Department of Chemistry, Zhejiang University, Hangzhou 310027, P. R. of China
› Author Affiliations
Further Information

Publication History

Received: 01 March 2014

Accepted: 22 March 2014

Publication Date:
10 April 2014 (online)

 
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Abstract

An efficient dual-catalyst system of piperidine and molecular iodine has been developed for the synthesis of 2-alkyl-2-(2-oxo-2H-chromen-3-yl)-2,3-dihydro-4(1H)quinazolinone derivatives by a four-component reaction of salicylaldehydes, β-keto esters, ammonium acetate, and isatoic anhydride. Good yields, mild reaction conditions, and easy purification are attractive features of the present method.


#

Key words

salicylaldehyde - β-keto ester - isatoic anhydride - ammonium acetate - 2-alkyl-2-(2-oxo-2H-chromen-3-yl)-2,3-dihydro-4(1H)quinazolinone - dual-catalyst system

Coumarins and their derivatives are very important structural motifs that occur widely in natural products.[1] Coumarins are widespread in animal and microbial metabolites and also in higher plants such as rutaceae, apiaceae, asteraceae, and thymelaeaceae.[2] They display a broad range of pharmacological properties such as antioxidant,[3] enzyme inhibition (aromatase, horseradish peroxidase, 17β-hydroxysteroid dehydrogenase type 3, etc.),[4] anti-HIV,[5] anti-inflammatory,[6] and antifungal.[7] Coumarins have also been used in the preparation of insecticides,[8] optical brighteners,[9] and triplet sensitizers.[10] Among these, 3-substituted coumarins are among the most important skeletons that are present in drug and drug candidates such as AP2238 (anti-Alzheimer drug candidate),[11] carbochromen (coronary heart disease treatment),[12] and warfarin (anticoagulant).[13] Despite the long history, due to the wide-ranging biological activity of coumarin derivatives, both naturally occurring and synthetic, the synthesis of this important ring system is still of interest and there are many reports for synthesis of these heterocycles.[14]

Quinazoline and its derivatives are biologically important compounds which exist as the core backbone in lots of natural pruducts.[15] Quinazolines possess a wide range of biological activities like antitumor,[16] anticonvulsant,[17] and antiplasmodial.[18] Among these, 2,3-dihydroquinazolinones are an important class of biologically compounds such as antitremor, antifertility, and antibacterial.[19] They have also been evaluated as antagonists of various biological receptors such as calcitonin gene related peptide, 5-HT5A related diseases, and vasopressin V3 receptors.[20] Due to their biological properties, 2,3-dihydroquinazolinone derivatives have attracted considerable attention and a range of methods has been reported for their synthesis.[21]

In recent years, molecular iodine has been used as a catalyst in organic synthesis due to its availability, low cost, and high tolerence to air and moisture.[22] Recently, molecular iodine has been used for the synthesis of quinazoline derivatives[23] from reaction between 2-aminobenzamide and various kinds of aldehydes and ketones. Accordingly and in continuation of our studies on the synthesis of new coumarin derivatives and investigation of molecular iodine in the synthesis of various heterocycles compounds,[24] we decided to synthesize coumarin bearing 2,3-dihydroquinazolinone by the reaction of salicylaldehydes 1, β-keto esters 2, isatoic anhydride, and ammonium acetate catalyzed by piperidine and molecular iodine as a dual-catalyst system.

To test this new process, initially we chose the reaction of salicylaldehyde, methyl acetoacetate, isatoic anhydride, and ammonium acetate as a model reaction. To optimize the reaction conditions, we investigated various solvents, base, and acid catalysts. The best results were obtained for the reaction in DMF in the presence of piperidine (10 mol%) and molecular iodine (15%) at 60 °C for five hours.[25] The results are summarized in Table [1].

We also performed the model reaction in the absence of piperidine or molecular iodine but these failed to give the desired product (Table [1], entries 14 and 15). Moreover, increasing the amount of piperidine and iodine did not improve the yield (Table [1], entries 7 and 9), while decreasing these amounts led to reduced yield (Table [1], entries 6 and 8). To explore the generality of the reaction, we extended our study with different salicylaldehydes 1 and β-keto esters 2. This protocol tolerates a variety of salicylaldehydes containing both electron-withdrawing and electron-donating substituents. The results are summarized in Table [2]. We also examined methyl 4-methyl-3-oxopentanoate (Table [2], entry 9) and methyl 4,4-dimethyl-3-oxopentanoate (Table [2], entry 10) in this protocol, but this failed to afford the desired products, probably it is related to high steric effect of the R2 group.

Table 1 Optimization of the Reaction Conditions

Entry

Solvent

Base (mol%)

Acids (mol%)

Yield (%)

 1

DMF

DABCO (10)

I2 (15)

–

 2

DMF

piperidine (10)

I2 (15)

84

 3

DMF

Et3N (10)

I2 (15)

–

 4

MeCN

piperidine (10)

I2 (15)

50

 5

EtOH

piperidine (10)

I2 (15)

65

 6

DMF

piperidine (5)

I2 (15)

55

 7

DMF

piperidine (15)

I2 (15)

84

 8

DMF

piperidine (10)

I2 (10)

40

 9

DMF

piperidine (10)

I2 (20)

85

10

DMF

piperidine (10)

FeCl3 (15)

trace

11

DMF

piperidine (10)

CuCl2 (15)

trace

12

DMF

piperidine (10)

BF3 (15)

30

13

DMF

piperidine (10)

PTSA (15)

–

14

DMF

piperidine (10)

–

–

15

DMF

–

I2 (15)

–

Table 2 One-Pot, Four-Component Synthesis of 2-Alkyl-2-(2-oxo-2H-chromen-3-yl)-2,3-dihydro-4(1H)quinazolinone Derivatives 3a–j

Entry

Products

Compound 1

R2

Yield (%)

 1

3a

salicylaldehyde

Me

84

 2

3b

3-methoxysalicylaldehyde

Me

77

 3

3c

5-methylsalicylaldehyde

Me

65

 4

3d

3,5-dichlorosalicylaldehyde

Me

87

 5

3e

3,5-bromosalicylaldehyde

Me

90

 6

3f

salicylaldehyde

n-Pr

65

 7

3g

3-methoxysalicylaldehyde

n-Pr

59

 8

3h

2-hydroxynaphthalene-1-carbaldehyde

Me

83

 9

3i

salicylaldehyde

i-Pr

Trace

10

3j

salicylaldehyde

t-Bu

–

The molecular structures of all products 3a–h were deduced from their elemental analyses, IR, mass, 1H NMR, and 13C NMR spectra as described for 3g. The mass spectrum of 3g displays a peak at m/z = 321 which is related to elimination of propyl group from the molecular structure. In the IR spectrum of 3g, absorption bands at 3375, 3238, 1696, 1659, 1610, 1477, 1272, and 1176 cm–1, related to 2 NH, CO2 and CONH, C=C, and C–O stretching frequencies, respectively, clearly indicated the most significant functional groups of the product. The 1H NMR spectrum of 3g exhibited one triplet at δ = 0.91 ppm for CH3 and four multiplets signals at δ = 1.47–1.52, 1.53–1.61, 1.92–1.99, and 2.11–2.19 ppm for CH2 groups of propyl because these hydrogens are diastereotopic. Four singlets at δ = 3.86, 7.08, 7.80, and 8.30 ppm are related to OCH3, NHCO, CH of coumarin ring and NH. Seven aromatic hydrogens are also shown one triplet at δ = 6.63 ppm, two doublets at δ = 6.88 and 7.56 ppm and one multiplet at δ = 7.16–7.25 ppm.

The 1H-decoupled 13C NMR spectrum of 3g showed 21 distinct signals in agreement with the suggested structure. In the aliphatic region there are four resonances at δ = 13.9, 16.6, 39.5, and 56.1 ppm which is related to the propyl and methoxy groups, respectively. Resonance due to CO2 and CONH appeared at δ = 158.7 and 163.5 ppm, respectively. The most important peak is related to C2 of quinazolinone ring which appeared at δ = 72.2 ppm (see Supporting Information). Final confirmation for the formation of the reaction products were derived from X-ray analysis of compound 3g. The ORTEP diagram of crystallography for compound 3g is shown in Figure [2].

Zoom Image
Figure 2 ORTEP diagram of 3g

A plausible mechanism for the synthesis of product 3a has been proposed in Scheme [1]. The isatoic anhydride is first converted into 2-aminobenzamide (4a). Then the Knoevenagel condensation and cyclization between salicylaldehydes 1 and β-keto esters 2 in the presence of piperidine leads to 3-acetylcoumarins 5a.[26] Next, condensation reaction between 4a and 5a in the presence of iodine leads to 6a. Finally, nucleophilic attack of the NH2 of amide to the imine group leads to the desired product 3a.

Zoom Image
Scheme 1 Proposed mechanism for the formation of 3

To investigate the proposed mechanism, 3-acetylcoumarin was synthesized separately and it was added to the 2-aminobenzamide solution in the presence of iodine, and the same product was obtained. For more information about the proposed mechanism, we examined the reaction between 3-acetylcoumarin and 2-aminobenzamide in the absence of molecular iodine, and we observed that there was no significant change in the reaction mixture. It seems that molecular iodine plays two important roles in this reaction, formation of imine 6a, potentially by coordinating to the carbonyl group and activation of imine group for further nucleophilic addition (Scheme [1]). In another attempt, we investigated the effect of molecular iodine in the formation of intermediates 4a and 5a, and we did not observe significant change in the reaction mixture. It seems the formation of both of them is fast and the molecular iodine would not effect on the rate of their formation.

In summary, we have presented a powerful and efficient method for the synthesis of 2-alkyl-2-(2-oxo-2H-chromen-3-yl)-2,3-dihydro-4(1H)quinazolinone derivatives by the reaction between salicylaldehyde, β-keto esters, isatoic anhydride, and ammonium acetate by piperidine and molecular iodine as a dual-catalyst system. Mild reaction conditions, ease of handling, easy workup, and good yields are the main features of this method. Due to the importance of both coumarin and quinazolinone moieties, 2-alkyl-2-(2-oxo-2H-chromen-3-yl)-2,3-dihydro-4(1H)-quinazolinone derivatives can be considered for biological application in the near future.


#

Supporting Information

    for this article is available online at http://www.thieme-connect.com.accesdistant.sorbonne-universite.fr/ejournals/toc/synlett.
  • Supporting Information

  • References and Notes

  • 1 Murray RD. H In Progress in the Chemistry of Organic Natural Products . Vol. 83. Herz W, Falk H, Kirby GW, Moore RE. Springer Verlag; Wien: 2002: 1-529
    Search in Google Scholar
  • 2 Murray RD. H, Mendez J, Brown SA. The Natural Coumarins: Occurrence, Chemistry and Biochemistry . John Wiley and Sons; New York: 1982: 21
    Search in Google Scholar
  • 3 Kontogiorgis C, Hadjipavlou-Litina D. J. Enzyme Inhib. Med. Chem. 2003; 18: 63
    CrossrefSearch in Google Scholar
  • 5 Kirkiacharian S, Thuy DT, Sicsic S, Bakhchinian R, Kurkjian R, Tonnaire T. Farmaco 2002; 57: 703
    CrossrefSearch in Google Scholar
  • 8 Kennedy RO, Zhorenes RD. Coumarins: Biology, Applications and Mode of Action . John Wiley and Sons; Chichester: 1997
    Search in Google Scholar
  • 9 Zabradnik M. The Production and Application of Fluorescent Brightening Agents. John Wiley and Sons; New York: 1992
    Search in Google Scholar
  • 11 Piazzi L, Rampa A, Bisi A, Gobbi S, Belluti F, Cavalli A, Bartolini M, Andrisano V, Valenti P, Recanatini M. J. Med. Chem. 2003; 46: 2279
    CrossrefSearch in Google Scholar
  • 12 Opherk D, Schuler G, Waas W, Dietz R, Kubler W. Eur. Heart J. 1990; 11: 342
    Search in Google Scholar
  • 13 Cao YG, Liu XQ, Chen YC, Hao K, Wang GJ. Eur. J. Pharm. Sci. 2007; 30: 175
    CrossrefSearch in Google Scholar
  • 16 Noolvi MN, Patel HM, Bhardwaj V, Chauhan A. Eur. J. Med. Chem. 2011; 46: 2327
    CrossrefPubMedSearch in Google Scholar
  • 17 El-Helby AG. A, Wahab MH. A. Acta Pharm. 2003; 53: 127
    Search in Google Scholar
  • 18 Kabri Y, Azas N, Dumètre A, Hutter S, Laget M, Verhaghe P, Gellis A, Vanlee P. Eur. J. Med. Chem. 2010; 45: 616
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    • 20a Alanine A, Gobbi LC, Kolczewski S, Luebbers T, Peters JU, Steward L. US 2006293350 A1, 2006 ; Chem. Abstr. 2006, 146, 100721
    • 20b Chaturvedula PV, Chen L, Civiello R, Degnan AP, Dubowchik GM, Han X, Jiang XJ, Macor JE, Poindexter GS, Tora GO, Luo G. US 2007149503 A1, 2007 ; Chem. Abstr. 2007, 147, 118256
    • 20c Letourneau J, Riviello C, Ho KK, Chan JH, Ohlmeyer M, Jokiel P, Neagu I, Morphy JR, Napier SE. WO 2006095014 A1, 2006 ; Chem. Abstr. 2006, 145, 315012
  • 25 To a solution of isatoic anhdyride (1 mmol) in DMF (2 mL) was added NH4OAc (1 mmol), and the solution was stirred for 15 min at 60 °C. Then, salicylaldehyde 1 (1 mmol), β-keto ester 2 (1 mmol), and piperidine (0.1 mmol) were added, and the solution was stirred. After 10 min molecular iodine (0.15 mmol) was added to the reaction mixture, and the reaction was stirred about 5 h. Upon completion (monitored by TLC) the solvent was evaporated under reduced pressure, and the residue was recrystallized from EtOH to afford the pure product 3a–h. 2-Methyl-2-(2-oxo-2H-chromen-3-yl)-2,3-dihydro-4(1H)quinazolinone (3a) White powder; 0.257 g, 84% yield; mp 298 °C (decomp.). IR (KBr): 3441 and 3169 (2 NH), 1717 (C=O), 1664 (CONH), 1609, 1570 and 1525 (Ar), 1199 (CO) cm–1. 1H NMR (400 MHz, DMSO-d 6): δ = 1.81 (s, 3 H, CH3), 6.65 (t, 3 J HH = 7.6 Hz, 1 H, CH of Ar), 6.86 (d, 3 J HH = 8.0 Hz, 1 H, CH of Ar), 7.18 (s, 1 H, NH), 7.24 (td, 3 J HH = 7.6 Hz, 4 J HH = 1.6 Hz, 1 H, CH of Ar), 7.33 (t, 3 J HH = 7.6 Hz, 1 H, CH of Ar), 7.39 (d, 3 J HH = 8.4 Hz, 1 H, CH of Ar), 7.56 (d, 3 J HH = 8.0 Hz, 1 H, CH of Ar), 7.60 (td, 3 J HH = 7.6 Hz, 4 J HH = 1.6 Hz, 1 H, CH of Ar), 7.73 (dd, 3 J HH = 7.6 Hz, 4 J HH = 1.2 Hz, 1 H, CH of Ar), 7.84 (1 H, s, CH4 of coumarin), 8.46 (s, 1 H, NH). 13C NMR (100 MHz, DMSO-d 6): δ = 26.5 (CH3), 69.2 (C2 of quinazoline), 114.1 (C3 of coumarin), 114.6 (CH of Ar), 115.9 (CH of Ar), 117.5 (CH of Ar), 118.0 (C4a of coumarin), 124.8 (CH of Ar), 127.2 (CH of Ar), 128.7 (CH of Ar), 131.0 (C4a of quinazoline), 132.1 (CH of Ar), 133.5 (CH of Ar), 138.6 (CH4 of coumarin), 146.2 (C8a of quinazoline), 152.7 (C8a of coumarin), 159.0 (CO2), 163.2 (CONH). MS: m/z = 264, 173, 145, 132, 118, 101, 89, 63. Anal. Calcd for C18H14N2O3: C, 70.58; H, 4.61; N, 9.15. Found: C, 70.81; H, 4.69; N, 8.99. 2-(8-Methoxy-2-oxo-2H-chromen-3-yl)-2-methyl-2,3-dihydro-4(1H)-quinazolinone (3b) Beige powder; 0.259 g, 77% yield; mp 247–249 °C. IR (KBr): 3345 and 3188 (2 NH), 1706 (C=O), 1650 (CONH), 1612 and 1478 (Ar), 1276 and 1184 (CO) cm–1. 1H NMR (400 MHz, DMSO-d 6): δ = 1.81 (s, 3 H, CH3), 3.88 (s, 3 H, OCH3), 6.65 (t, 3 J HH = 7.4 Hz, 1 H, CH of Ar), 6.85 (d, 3 J HH = 8.0 Hz, 1 H, CH of Ar), 7.17 (s, 1 H, NH), 7.24–7.29 (m, 4 H, CH of Ar), 7.56 (dd, 3 J HH = 7.8 Hz, 4 J HH = 1.4 Hz, 1 H, CH of Ar), 7.81 (s, 1 H, CH4 of coumarin), 8.44 (s, 1 H, NH). 13C NMR (100 MHz, DMSO-d 6): δ = 26.4 (CH3), 56.1 (OCH3), 69.2 (C2 of quinazoline), 114.1 (C3 of coumarin), 114.3 (CH of Ar), 114.6 (CH of Ar), 117.5 (CH of Ar), 118.6 (C4a of coumarin), 119.8 (CH of Ar), 124.8 (CH of Ar), 127.2 (CH of Ar), 131.2 (C4a of quinazoline), 133.5 (CH of Ar), 138.8 (CH4 of coumarin), 142.1 (C8a of coumarin), 146.1 (C8a of quinazoline), 146.2 (C ipso -OCH3), 158.7 (CO2), 163.2 (CONH). MS: m/z (%) = 336 (5) [M+], 321 (67), 161 (100), 120 (76), 92 (81), 76 (26), 65 (43). Anal. Calcd for C19H16N2O4: C, 67.85; H, 4.79; N, 8.33. Found: C, 77.69; H, 4.88; N, 8.21.
  • 26 Frolova LV, Malik I, Uglinskii PY, Rogelj S, Kornienko A, Magedov IV. Tetrahedron Lett. 2011; 52: 6643
    CrossrefSearch in Google Scholar

  • References and Notes

  • 1 Murray RD. H In Progress in the Chemistry of Organic Natural Products . Vol. 83. Herz W, Falk H, Kirby GW, Moore RE. Springer Verlag; Wien: 2002: 1-529
    Search in Google Scholar
  • 2 Murray RD. H, Mendez J, Brown SA. The Natural Coumarins: Occurrence, Chemistry and Biochemistry . John Wiley and Sons; New York: 1982: 21
    Search in Google Scholar
  • 3 Kontogiorgis C, Hadjipavlou-Litina D. J. Enzyme Inhib. Med. Chem. 2003; 18: 63
    CrossrefSearch in Google Scholar
  • 5 Kirkiacharian S, Thuy DT, Sicsic S, Bakhchinian R, Kurkjian R, Tonnaire T. Farmaco 2002; 57: 703
    CrossrefSearch in Google Scholar
  • 8 Kennedy RO, Zhorenes RD. Coumarins: Biology, Applications and Mode of Action . John Wiley and Sons; Chichester: 1997
    Search in Google Scholar
  • 9 Zabradnik M. The Production and Application of Fluorescent Brightening Agents. John Wiley and Sons; New York: 1992
    Search in Google Scholar
  • 11 Piazzi L, Rampa A, Bisi A, Gobbi S, Belluti F, Cavalli A, Bartolini M, Andrisano V, Valenti P, Recanatini M. J. Med. Chem. 2003; 46: 2279
    CrossrefSearch in Google Scholar
  • 12 Opherk D, Schuler G, Waas W, Dietz R, Kubler W. Eur. Heart J. 1990; 11: 342
    Search in Google Scholar
  • 13 Cao YG, Liu XQ, Chen YC, Hao K, Wang GJ. Eur. J. Pharm. Sci. 2007; 30: 175
    CrossrefSearch in Google Scholar
  • 16 Noolvi MN, Patel HM, Bhardwaj V, Chauhan A. Eur. J. Med. Chem. 2011; 46: 2327
    CrossrefPubMedSearch in Google Scholar
  • 17 El-Helby AG. A, Wahab MH. A. Acta Pharm. 2003; 53: 127
    Search in Google Scholar
  • 18 Kabri Y, Azas N, Dumètre A, Hutter S, Laget M, Verhaghe P, Gellis A, Vanlee P. Eur. J. Med. Chem. 2010; 45: 616
    CrossrefSearch in Google Scholar
    • 20a Alanine A, Gobbi LC, Kolczewski S, Luebbers T, Peters JU, Steward L. US 2006293350 A1, 2006 ; Chem. Abstr. 2006, 146, 100721
    • 20b Chaturvedula PV, Chen L, Civiello R, Degnan AP, Dubowchik GM, Han X, Jiang XJ, Macor JE, Poindexter GS, Tora GO, Luo G. US 2007149503 A1, 2007 ; Chem. Abstr. 2007, 147, 118256
    • 20c Letourneau J, Riviello C, Ho KK, Chan JH, Ohlmeyer M, Jokiel P, Neagu I, Morphy JR, Napier SE. WO 2006095014 A1, 2006 ; Chem. Abstr. 2006, 145, 315012
  • 25 To a solution of isatoic anhdyride (1 mmol) in DMF (2 mL) was added NH4OAc (1 mmol), and the solution was stirred for 15 min at 60 °C. Then, salicylaldehyde 1 (1 mmol), β-keto ester 2 (1 mmol), and piperidine (0.1 mmol) were added, and the solution was stirred. After 10 min molecular iodine (0.15 mmol) was added to the reaction mixture, and the reaction was stirred about 5 h. Upon completion (monitored by TLC) the solvent was evaporated under reduced pressure, and the residue was recrystallized from EtOH to afford the pure product 3a–h. 2-Methyl-2-(2-oxo-2H-chromen-3-yl)-2,3-dihydro-4(1H)quinazolinone (3a) White powder; 0.257 g, 84% yield; mp 298 °C (decomp.). IR (KBr): 3441 and 3169 (2 NH), 1717 (C=O), 1664 (CONH), 1609, 1570 and 1525 (Ar), 1199 (CO) cm–1. 1H NMR (400 MHz, DMSO-d 6): δ = 1.81 (s, 3 H, CH3), 6.65 (t, 3 J HH = 7.6 Hz, 1 H, CH of Ar), 6.86 (d, 3 J HH = 8.0 Hz, 1 H, CH of Ar), 7.18 (s, 1 H, NH), 7.24 (td, 3 J HH = 7.6 Hz, 4 J HH = 1.6 Hz, 1 H, CH of Ar), 7.33 (t, 3 J HH = 7.6 Hz, 1 H, CH of Ar), 7.39 (d, 3 J HH = 8.4 Hz, 1 H, CH of Ar), 7.56 (d, 3 J HH = 8.0 Hz, 1 H, CH of Ar), 7.60 (td, 3 J HH = 7.6 Hz, 4 J HH = 1.6 Hz, 1 H, CH of Ar), 7.73 (dd, 3 J HH = 7.6 Hz, 4 J HH = 1.2 Hz, 1 H, CH of Ar), 7.84 (1 H, s, CH4 of coumarin), 8.46 (s, 1 H, NH). 13C NMR (100 MHz, DMSO-d 6): δ = 26.5 (CH3), 69.2 (C2 of quinazoline), 114.1 (C3 of coumarin), 114.6 (CH of Ar), 115.9 (CH of Ar), 117.5 (CH of Ar), 118.0 (C4a of coumarin), 124.8 (CH of Ar), 127.2 (CH of Ar), 128.7 (CH of Ar), 131.0 (C4a of quinazoline), 132.1 (CH of Ar), 133.5 (CH of Ar), 138.6 (CH4 of coumarin), 146.2 (C8a of quinazoline), 152.7 (C8a of coumarin), 159.0 (CO2), 163.2 (CONH). MS: m/z = 264, 173, 145, 132, 118, 101, 89, 63. Anal. Calcd for C18H14N2O3: C, 70.58; H, 4.61; N, 9.15. Found: C, 70.81; H, 4.69; N, 8.99. 2-(8-Methoxy-2-oxo-2H-chromen-3-yl)-2-methyl-2,3-dihydro-4(1H)-quinazolinone (3b) Beige powder; 0.259 g, 77% yield; mp 247–249 °C. IR (KBr): 3345 and 3188 (2 NH), 1706 (C=O), 1650 (CONH), 1612 and 1478 (Ar), 1276 and 1184 (CO) cm–1. 1H NMR (400 MHz, DMSO-d 6): δ = 1.81 (s, 3 H, CH3), 3.88 (s, 3 H, OCH3), 6.65 (t, 3 J HH = 7.4 Hz, 1 H, CH of Ar), 6.85 (d, 3 J HH = 8.0 Hz, 1 H, CH of Ar), 7.17 (s, 1 H, NH), 7.24–7.29 (m, 4 H, CH of Ar), 7.56 (dd, 3 J HH = 7.8 Hz, 4 J HH = 1.4 Hz, 1 H, CH of Ar), 7.81 (s, 1 H, CH4 of coumarin), 8.44 (s, 1 H, NH). 13C NMR (100 MHz, DMSO-d 6): δ = 26.4 (CH3), 56.1 (OCH3), 69.2 (C2 of quinazoline), 114.1 (C3 of coumarin), 114.3 (CH of Ar), 114.6 (CH of Ar), 117.5 (CH of Ar), 118.6 (C4a of coumarin), 119.8 (CH of Ar), 124.8 (CH of Ar), 127.2 (CH of Ar), 131.2 (C4a of quinazoline), 133.5 (CH of Ar), 138.8 (CH4 of coumarin), 142.1 (C8a of coumarin), 146.1 (C8a of quinazoline), 146.2 (C ipso -OCH3), 158.7 (CO2), 163.2 (CONH). MS: m/z (%) = 336 (5) [M+], 321 (67), 161 (100), 120 (76), 92 (81), 76 (26), 65 (43). Anal. Calcd for C19H16N2O4: C, 67.85; H, 4.79; N, 8.33. Found: C, 77.69; H, 4.88; N, 8.21.
  • 26 Frolova LV, Malik I, Uglinskii PY, Rogelj S, Kornienko A, Magedov IV. Tetrahedron Lett. 2011; 52: 6643
    CrossrefSearch in Google Scholar

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Zoom Image
Figure 2 ORTEP diagram of 3g
Zoom Image
Scheme 1 Proposed mechanism for the formation of 3