Download PDF
Synlett 2008(2): 233-236  
DOI: 10.1055/s-2007-1000841
LETTER
© Georg Thieme Verlag Stuttgart · New York

Investigation of the Reaction of o-Aminonitriles with Ketones: A New Modification of Friedländer Reaction and Structures of Its Products

Jiarong Li*, Lijun Zhang, Daxin Shi, Qing Li, Dong Wang, Chunxia Wang, Qi Zhang, Ling Zhang, Yanqiu Fan
School of Chemical Engineering and Environment, Beijing Institute of Technology, 100081 Beijing, P. R. of China
Fax: +86(10)68913293; e-Mail: jrli@bit.edu.cn;
Further Information

Publication History

Received 22 September 2007
Publication Date:
11 December 2007 (online)

    Permissions and Reprints All articles of this category

Abstract

A new modification of the Friedländer reaction is described and the new byproduct obtained from the reaction of o-aminonitriles and ketones was found to be 2,3-dihydroquinazolin-4(1H)-one. The mechanism probably involved the formation of an intermediate oxazine, via the Pinner reaction and its transformation into new products via the Dimroth rearrangement.

Key words

Friedländer reactions - cyclizations - spiro compounds - rearrangements - molecular recognition

11

Typical Procedure for Preparation of Products 2 and 4: o-Aminonitrile 1 (1.5 mmol), cyclohexanone (1.7 mmol), anhyd zinc chloride (1.6 mmol) and DMF (10 mL) were added into a 50-mL flask. The reaction mixture was refluxed for 2 h (monitored by TLC). Then the mixture was diluted with H2O and titrated to pH 12-13 by 20% NaOH. After filtration, the solid was dissolved in THF, the organic phase obtained was combined with the extracted component of filtrate (using EtOAc) and evaporated in vacuo, and then chromatographed (Merck, 200-300 mesh, EtOAc-PE, 1:2) to afford product 2 and 4.Selected data for compounds 2, 4 and 8:14-(3-Nitrophenyl)-9,10,11,12-tetrahydro-14 H -naphtho[1′,2′:5,6]pyrano[2,3- b ]quinolin-13-amine (2a): yellow solid; mp 287-289 °C. IR (KBr): 3450, 3364, 2935, 1640, 1607, 1573, 1523, 1445, 1348, 1232 cm-1. 1H NMR: (400 MHz, CDCl3): δ = 1.80-1.86 (m, 4 H, CH2), 2.28-2.42 (m, 2 H, CH2), 2.82 (m, 2 H, CH2), 4.42 (s, 2 H, NH2), 5.76 (s, 1 H, CH), 7.34-7.40 (q, J = 8.0 Hz, 2 H, ArH), 7.46-7.51 (m, J = 8.0 Hz, 2 H, ArH), 7.72 (d, J = 7.9 Hz, 1 H, ArH), 7.79 (t, J = 7.9 Hz, 2 H, ArH), 7.98 (m, J = 2.0, 8.0 Hz, 2 H, ArH), 8.38 (t, J = 2.0 Hz, 1 H, ArH). 13C NMR (100 MHz, CDCl3): δ = 22.3, 22.4, 22.9, 32.4, 37.9, 99.3, 113.2, 114.9, 118.5, 121.8, 122.1 (2 × C), 124.3, 127.1, 128.9, 129.8, 129.9, 130.5, 130.8, 134.3, 145.6, 148.0, 149.0, 150.3, 154.5, 154.8. MS (ESI): m/z = 424.3 [M + H+]. Anal. Calcd for C26H21N3O3: C, 73.74; H, 5.00; N, 9.92. Found: C, 73.60; H, 5.05; N, 9.75.8,9,12-Trihydro-9,9-pentamethylene-12-(3-nitrophenyl)-11 H -naphtho[1′,2′:5,6]pyrano[2,3- d ]pyrimidin-11 (10 H )-one (4a): yellow solid; mp 275-278 °C. IR (KBr): 3187, 2937, 1659, 1630, 1527, 1349, 1227 cm-1. 1H NMR (400 MHz, DMSO-d 6): δ = 1.22 (m, 1 H, CH2), 1.38 (m, 4 H, CH2), 1.66 (m, 4 H, CH2), 1.76 (m, 1 H, CH2), 5.76 (s, 1 H, CH), 7.23 (s, 1 H, NH), 7.43-7.52 (m, J = 7.8 Hz, 4 H, ArH), 7.58 (s, 1 H, NH), 7.63 (d, J = 7.8 Hz, 1 H, ArH), 7.96 (m, J = 1.8, 7.8 Hz, 4 H, ArH), 8.12 (t, J = 1.8 Hz, 1 H, ArH). 13C NMR (100 MHz, DMSO-d 6): δ = 20.7, 21.1, 24.7, 34.3, 36.0, 36.3, 67.1, 81.6, 116.9, 117.0, 121.1, 121.9, 123.3, 125.0, 127.4, 128.6, 129.6, 129.9, 130.6, 130.8, 134.1, 147.6, 147.7, 148.8, 154.8, 165.5. MS (ESI): m/z = 442.3 [M + H+]. Anal. Calcd for C26H23N3O4: C, 70.73; H, 5.25; N, 9.52. Found: C, 70.45; H, 5.22; N, 9.61.6-Chloro-2,2-pentamethylene-1,2-dihydroquinazolin-4 (3 H )-one (8a): light yellow solid; mp 232-233 °C. IR (KBr): 3358, 3173, 2934, 2855, 1643, 1612, 1493, 825 cm-1. 1H NMR (DMSO-d 6): δ = 1.23-1.73 (m, 10 H, CH2), 6.63 (dd, J = 2.0, 8.0 Hz, 1 H, ArH), 6.86 (d, J = 2.0 Hz, 1 H, ArH), 6.90 (s, 1 H, NH), 7.54 (d, J = 8.0 Hz, 1 H, ArH), 8.05 (s, 1 H, NH). MS (ESI): m/z (%) = 264.2 (100) [M + H]+. Anal. Calcd for C13H15ClN2O (252.1): C, 62.28; H, 6.03; N, 14.14. Found: C, 62.19; H, 5.92; N, 14.11.2,2-Butamethylene-6-nitro-1,2-dihydroquinazolin-4 (3 H )-one (8b): mp 281-283 °C. IR (KBr): 3319, 3180, 2912, 1672, 1619, 1534, 1310 cm-1. 1H NMR (DMSO-d 6): δ = 1.67-1.88 (m, 8 H, C4H8), 6.82 (d, J = 8.0 Hz, 1 H, ArH), 8.10 (dd, J = 2.4, 8.0 Hz, 1 H, ArH), 8.30 (s, 1 H, NH), 8.42 (d, J = 2.4 Hz, 1 H, ArH), 8.56 (s, 1 H, NH). 13C NMR (DMSO-d 6): δ = 21.90 (2 × C), 40.15 (2 × C), 77.32, 112.31, 114.14, 124.11, 128.62, 136.68, 151.63, 161.21. MS (ESI): m/z (%) = 248.2 (100) [M + H]+. Anal. Calcd for C12H13N3O3: C, 58.29; H, 5.30; N, 16.99. Found: C, 58.33; H, 5.31; N, 17.08.

13

CCDC 660416 (4a) and CCDC 667600(4b) contain the supplementary crystallographic data for this paper. These data can be obtained free of charge from The Cambridge Crystallographic Data Centre via http://www.ccdc.cam.ac.uk/data_request/cif.

16

This new conversion is abbreviated as PDF conversion, which means a new conversion from Pinner to Dimroth rearrangement in the Friedländer reaction.