Mild, Efficient and Selective Silver Carbonate Mediated O-Alkylation of 4-Hydroxy-2-quinolones: Synthesis of 2,4-Dialkoxyquinolines

Ademir Farias Morel; Enrique L. Larghi; Marcel Manke Selvero

doi:10.1055/s-2005-918945

Subscribe to RSS

Please copy the URL and add it into your RSS Feed Reader.

https://www.thieme-connect.de/rss/thieme/en/10.1055-s-00000083.xml

Share / Bookmark

Facebook X Linkedin Weibo

Download PDF

Synlett 2005(18): 2755-2758
DOI: 10.1055/s-2005-918945

LETTER

Mild, Efficient and Selective Silver Carbonate Mediated O-Alkylation of 4-Hydroxy-2-quinolones: Synthesis of 2,4-Dialkoxyquinolines

Ademir Farias Morel^a, Enrique L. Larghi*^b, Marcel Manke Selvero^a
^a Departamento de Química, Universidade Federal de Santa Maria-UFSM, Campus UFSM, Santa Maria, RS - 97105-900, Brazil
Fax: +55(55)2208031; e-Mail: amorel@base.ufsm.br;
^b Instituto de Química Orgánica de Síntesis (CONICET-UNR), Suipacha 531, 2000 Rosario, Argentina
e-Mail: iquiosra@fbioyf.unr.edu.ar;

Further Information

Publication History

Received 5 August 2005
Publication Date:
12 October 2005 (online)

Abstract
Full Text
References

Permissions and Reprints All articles of this category

Abstract

The reaction of 4-hydroxy-2-quinolones with alkyl iodides, benzyl bromides and allyl bromides in benzene at room temperature, in the presence of Ag₂CO₃, afforded 2,4-dialkoxyquinolines in moderate to excellent yields. The process is highly regioselective and constitutes a new and mild one-pot alternative for the preparation of this class of compounds.

Key words

alkylation - 4-hydroxy-2-quinolones - silver carbonate - 2,4-dialkoxyquinolines

References

1a Arndt F. Ergener L. Kutlu O. Chem. Ind. (London) 1950, 465

Google Scholar
1b Reische J. Mester I. Arch. Pharm. (Weinheim, Ger.) 1980, 313: 751

Google Scholar
1c Buchman FJ. Hamilton CS. J. Am. Chem. Soc. 1942, 64: 1357

Google Scholar
1d Osborne AG. Warmsley JF. Dimitrova GT. J. Nat. Prod. 1990, 55: 589

Google Scholar
2a Comins DL. Jianhua G. Tetrahedron Lett. 1994, 35: 2819

Article in Thieme Connect Google Scholar
2b Diez-Barra AE. de la Hoz A. Synth. Commun. 1994, 24: 1057

Article in Thieme Connect Google Scholar
2c Liu H. Ko S.-B. Josien H. Curran DP. Tetrahedron Lett. 1995, 36: 8917

Article in Thieme Connect Google Scholar
2d Joseph B. Darro F. Béhard A. Lesur B. Collignon F. Decaestecker C. Frydman A. Guillaumet G. Kiss R. J. Med. Chem. 2002, 45: 2543

Article in Thieme Connect Google Scholar
2e Curran DP. Liu H. J. Am. Chem. Soc. 1992, 114: 5863

Article in Thieme Connect Google Scholar
2f Comins DL. Baevsky MF. Hong H. J. Am. Chem. Soc. 1992, 114: 10971

Article in Thieme Connect Google Scholar
2g Sato T. Yoshimatsu K. Otera J. Synlett 1995, 845

Article in Thieme Connect Google Scholar
3 Kornblum N. Smiley RA. Blackwood RK. Iffland DC. J. Am. Chem. Soc. 1955, 77: 6269 ; and references cited therein

Crossref Google Scholar
4a Hopkins GC. Jonak JP. Minnemeyer HJ. Tieckelmann H. J. Org. Chem. 1967, 32: 4040

Crossref Google Scholar
4b Hopkins GC. Jonak JP. Minnemeyer HJ. Tieckelmann H. J. Org. Chem. 1966, 31: 3969

Crossref Google Scholar
5a Tomchin AB. Shirokii GA. Dmitrukha VS. Khim. Geterotsikl. Soedin. 1976, 83 ; Chem. Abstr. 1976, 84, 179383m

Crossref Google Scholar
5b Da Silva JFM. Garden SJ. Pinto AC. J. Braz. Chem. Soc. 2001, 12: 273

Crossref Google Scholar
6a Freeman GA. Webster-Andrews C. Hopkins AL. Lowell GS. Schaller LT. Cowan JR. Gonzáles SS. Koszalka GW. Hazen RJ. Boone LR. Ferris RG. Creech KL. Roberts GB. Short SA. Weaver K. Reynolds DJ. Milton J. Ren J. Stuart DI. Stammers DK. Chan JH. J. Med. Chem. 2004, 47: 5923

Crossref Google Scholar
6b Youngdale GA. Oglia TF. J. Med. Chem. 1985, 28: 1790

Crossref Google Scholar
7a Baldwin JE. Adlington RM. Conte A. Irlapati NR. Marquez R. Pritchard GJ. Org. Lett. 2002, 4: 2125

Article in Thieme Connect Google Scholar
7b Wei ZL. Petukhov PA. Xiao Y. Tuckmantel W. George C. Kellar KJ. Kozikowski AP. J. Med. Chem. 2003, 46: 921

Article in Thieme Connect Google Scholar
7c Trécourt F. Mallet M. Mongin O. Quéguiner G. J. Heterocycl. Chem. 1995, 32: 1117

Article in Thieme Connect Google Scholar
7d Chung MC. Tieckelmann H. J. Org. Chem. 1970, 35: 2517

Article in Thieme Connect Google Scholar
7e Peukert F. Schwahn U. Güssregen S. Schreuder H. Hofmeister A. Synthesis 2005, 1550

Article in Thieme Connect Google Scholar
7f McGee KF. Al-Tel TH. Sieburth SM. Synthesis 2001, 1185

Article in Thieme Connect Google Scholar
8a Narasimhan NS. Paradkar MV. Alurkar RH. Tetrahedron 1971, 27: 1351

Crossref Google Scholar
8b Collins JF. Gray GA. Grundon MF. Harrison DM. Spyropoulos CG. J. Chem. Soc., Perkin Trans. 1 1973, 94

Crossref Google Scholar
8c Narasimhan NS. Bhagwat SP. Synthesis 1979, 903

Crossref Google Scholar
8d Boyd DR. Sharma ND. Barr SA. Carroll JG. Mackerrecher D. Malone JF. J. Chem. Soc., Perkin Trans. 1 2000, 3397

Crossref Google Scholar
8e Jones K. Roset X. Rossiter S. Whitefield P. Org. Biomol. Chem. 2003, 1: 4380

Crossref Google Scholar
9a Ulubelen A. J. Nat. Prod. 1990, 53: 207

Google Scholar
9b Cuca LE. Martinez JC. Delle Monache F. Rev. Col. Quím. 1998, 27: 13

Google Scholar
9c Cuca LE. Martinez JC. Delle Monache F. J. Braz. Chem. Soc. 2002, 13: 339

Google Scholar
10 Reisch J. Iding M. Schönweiler D. J. Heterocycl. Chem. 1993, 30: 861

Google Scholar
11a Narasimhan NS. Mali RS. Tetrahedron 1974, 30: 4153

Google Scholar
11b Nickel P. Barnickel H. Preissinger L. Fink E. Dann O. Arzneim.-Forsch. 1978, 28: 367

Google Scholar
11c Belli ML. Illuminati G. Marino G. Tetrahedron 1963, 19: 345

Google Scholar
11d Osborne AG. Miller LAD. J. Chem. Soc., Perkin Trans. 1 1993, 181

Google Scholar
11e Osborne AG. Buley JM. Clarke H. Dakin RCH. Price PI. J. Chem. Soc., Perkin Trans. 1 1993, 2747

Google Scholar
11f Tagawa Y. Kawaoka T. Goto Y. J. Heterocycl. Chem. 1997, 34: 1677

Google Scholar
For approaches to the syntheses of 4-hydroxy-2-quinolones, see:
12a Shobana N. Yeshoda P. Shanmugan P. Tetrahedron 1989, 45: 757

Google Scholar
12b Fischer M. Laschober R. Preiß A. Kappe T. Sci. Pharm. 1996, 64: 353

Google Scholar
12c Ziegler E. Gelfert K. Monatsh. Chem. 1959, 90: 822

Google Scholar
12d Kappe T. Karem AS. Stadlbauer W. J. Heterocycl. Chem. 1988, 25: 857

Google Scholar

13

General Procedure for the Dialkylation of 4-Hydroxy-2-quinolones. To a suspension of 2,4-dihydroxyquinoline (1 mmol) [12] in anhyd benzene (5 mL) was added Ag₂CO₃ (2 mmol) under an Argon atmosphere and the resulting slurry was homogenized by magnetic stirring at r.t. for 5 min, giving a yellowish suspension. Then, the halide (4 mmol) was added dropwise to the suspension and the mixture was further stirred at r.t. for 3 d in the dark. After this period the suspension was diluted with EtOAc, filtered through Celite, and the remaining greenish solid was washed 5 times with small portions of EtOAc. After evaporation of the volatiles, the product was isolated by silica gel (230-400 mesh) column chromatography, eluting with mixtures of hexanes and EtOAc.

14

Selected physical and spectral data for the synthesized 2,4-dialkoxyquinolines.
2,4-Dimethoxyquinoline (2a): white solid, mp 79-81 °C (hexane-EtOAc); lit. 81-82 °C. [1a]
2,4-Diethoxyquinoline (2b): white solid, mp: 55-56 °C (hexane-CH₂Cl₂); lit. 55-56 °C. [1c]
2,4-Bis(pentyloxy)quinoline (2c): yellowish oil. IR (film): 2930, 2860, 1900, 1600, 1570, 1410, 1340, 1180, 1100, 820, 760 cm^-1. ¹H NMR (200 MHz, CDCl₃): δ = 8.05 (d, J = 7.6 Hz, 1 H), 7.75 (d, J = 7.9 Hz, 1 H), 7.56 (t, J = 6.9 Hz, 1 H), 7.29 (t, J = 7.9 Hz, 1 H), 6.18 (s, 1 H), 4.45 (t, J = 6.6 Hz, 2 H), 4.09 (t, J = 6.3 Hz, 2 H), 1.85 (m, 4 H), 1.45 (m, 8 H), 0.95 (m, 6 H). ¹³C NMR (50 MHz, CDCl₃): δ = 163.7, 163.1, 147.2, 129.7, 128.5, 126.8, 123.2, 122.9, 121.8, 119.3, 91.3, 68.4, 65.9, 28.8, 28.5, 28.3, 28.2, 22.5, 22.4, 13.9. HRMS (FAB): m/z calcd for C₁₉H₂₇NO₂: 302.21200. Found: 302.21094 [M⁺ + H]. Anal. Calcd for C₁₉H₂₇NO₂: C, 75.71; H, 9.03; N, 4.65. Found: C, 76.11; H, 9.15; N, 4.57.
2,4-Diisopropoxyquinoline (2d): colorless oil. IR (film): 2980, 1600, 1570, 1400, 1320, 1200, 1120, 1010, 920, 830, 760 cm^-1. ¹H NMR (200 MHz, CDCl₃): δ = 7.97 (ddd, J = 8.2, 1.5, 0.4 Hz, 1 H), 7.70 (d, J = 8.4 Hz, 1 H), 7.51 (ddd, J = 8.4, 6.9, 1.5 Hz, 1 H), 7.33 (ddd, J = 8.2, 6.9, 1.2 Hz, 1 H), 6.10 (s, 1 H), 5.54 (sept, J = 6.3 Hz, 1 H), 4.67 (sept, J = 6.0 Hz, 1 H), 1.40 (d, J = 6.0 Hz, 6 H), 1.34 (d, J = 6.3 Hz, 6 H). ¹³C NMR (50 MHz, CDCl₃): δ = 163.0, 162.1, 147.2, 129.7, 126.7, 122.8, 122.0, 119.6, 92.3, 70.7, 67.9, 22.1, 21.7. MS (EI): m/z (%) = 245 [M⁺], 230, 203, 187, 161 (100), 145, 119, 77, 43.

Ethyl[2-(2-oxopentyloxy)quinolin-4-yloxy]acetate (2e): yellowish oil. IR (film): 2990, 2940, 1760, 1730, 1620, 1600, 1580, 1400, 1370, 1210, 1170, 1030, 760 cm^-1. ¹H NMR (200 MHz, CDCl₃): δ = 8.16 (dd, J = 8.2, 1.1 Hz, 1 H), 7.99 (dd, J = 8.0, 1.3 Hz, 1 H), 7.60 (m, 2 H), 7.39 (m, 2 H), 6.26 (s, 1 H), 5.04 (s, 2 H), 5.02 (s, 2 H), 4.81 (s, 2 H), 4.73 (s, 2 H), 4.32-4.11 (m, 10 H), 3.97 (s, 2 H), 1.34-1.24 (m, 15 H). ¹³C NMR (50 MHz, CDCl₃): δ = 171.8, 169.2, 168.9, 168.4, 167.4, 162.6, 161.7, 161.5, 160.1, 146.3, 146.2, 130.4, 129.8, 127.6, 126.8, 124.5, 124.0, 122.1, 122.0, 120.8, 119.1, 91.3, 71.4, 65.3, 63.0, 62.9, 61.7, 61.5, 61.1, 61.0, 60.9, 60.4, 30.1, 14.1. MS (EI): m/z (%) = 333 [M⁺], 288, 260 (100), 232, 174, 158, 130, 116, 89.
2,4-Bis(benzyloxy)quinoline (2g): white solid; mp 54-56 °C (hexane-EtOAc). IR (KBr): 2924, 1621, 1603, 1576, 1405, 1345, 1183, 1107, 1024, 821, 764, 731, 697 cm^-1. ¹H NMR (200 MHz, CDCl₃): δ = 7.99 (d, J = 8.0 Hz, 1 H), 7.68 (d, J = 8.3 Hz, 1 H), 7.50-7.06 (m, 12 H), 6.21 (s, 1 H), 5.40 (s, 2 H), 5.04 (s, 2 H). ¹³C NMR (50 MHz, CDCl₃): δ = 163.1, 162.9, 147.0, 137.4, 135.8, 129.9, 128.7, 128.4, 128.3, 127.8, 127.4, 126.9, 123.4, 121.1, 119.4, 91.9, 70.2, 67.7. MS (EI): m/z (%) = 341 [M⁺], 250, 235, 91 (100).
2,4-Bis(allyloxy)quinoline (2h): colorless oil. IR (film): 2990, 2940, 1760, 1730, 1620, 1600, 1580, 1400, 1370, 1210, 1170, 1030, 760 cm^-1. ¹H NMR (200 MHz, CDCl₃): δ = 8.10 (dd, J = 8.2, 1.2 Hz, 1 H), 7.81 (d, J = 8.4 Hz, 1 H), 7.61 (ddd, J = 8.4, 7.0, 1.2 Hz, 1 H), 7.33 (ddd, J = 8.2, 7.0, 1.3 Hz, 1 H), 6.26 (s, 1 H), 6.17-6.11 (m, 2 H), 5.54-5.28 (m, 4 H), 5.02 (d, J = 5.3 Hz, 2 H), 4.72 (d, J = 5.3 Hz, 2 H). ¹³C NMR (50 MHz, CDCl₃): δ = 162.8, 162.7, 146.9, 133.6, 131.9, 129.9, 126.8, 123.3, 121.9, 119.3, 118.3, 117.6, 91.6, 68.9, 66.7. MS (EI): m/z = 241 [M⁺], 226, 200, 184, 158, 69, 41.
2,4,6-Trimethoxyquinoline (2i): mp 78-79 °C (hexane-EtOAc); lit. 79 °C. [9a]
2,4,8-Trimethoxyquinoline (2j): mp 150-152 °C (hexane-CH₂Cl₂); lit. 152 °C. [9a]
2,4-Dimethoxy-8-methylquinoline (2k): mp 45-47 °C (hexane-EtOAc). IR (KBr): 2960, 1620, 1590, 1450, 1410, 1360, 1210, 1160, 1060, 820, 800, 760 cm^-1. ¹H NMR (200 MHz, CDCl₃): δ = 7.84 (d, J = 7.7 Hz, 1 H), 7.40 (d, J = 7.2 Hz, 1 H), 7.15 (dd, J = 7.7, 7.2 Hz, 1 H), 6.15 (s, 1 H), 3.99 (s, 3 H), 3.90 (s, 3 H), 2.61 (s, 3 H). ¹³C NMR (50 MHz, CDCl₃): δ = 164.1, 162.5, 145.8, 134.9, 130.1, 122.7, 119.4, 118.9, 90.1, 55.6, 53.1, 17.9. HRMS (FAB): m/z calcd for C₁₂H₁₄NO₂: 204.10245. Found: 204.10184 [M⁺ + H].