Synlett 2002(12): 2043-2044
DOI: 10.1055/s-2002-35592
LETTER
© Georg Thieme Verlag Stuttgart · New York

Efficient Synthesis of 5-Hydroxymethyl Pyrimidines and their Nucleosides Using Microwave Irradiation

Adel A.-H. Abdel-Rahmana, El S. H. El Ashry*b
a Department of Chemistry, Faculty of Science, Menoufia University, Shebin El-Koam
b Department of Chemistry, Faculty of Science, Alexandria University, Alexandria, Egypt
Fax: +20(3)4271360; e-Mail: eelashry@link.net; e-Mail: eelashry60@hotmail.com;
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Publikationsverlauf

Received 1 October 2002
Publikationsdatum:
20. November 2002 (online)

Abstract

Hydroxymethylation of uracil (1), cytosine (3), 5-hydroxymethyl-2′,3′-O-isopropylideneuridine (5), 5′-O-tert-butyldiphenylsilyl-2′,3′-O-isopropylideneuridine (7), 2′,3′-O-isopropyl-idenecytidine (9) and 2′,3′-O-isopropylidene-5′-O-tritylcytidine (11) was efficiently carried out with paraformaldehyde in alkaline medium under microwave irradiation in very high yield.

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Selected Physical Data: 2: White powder; mp >300 °C (H2O); TLC (CHCl3-MeOH, 8.5:1.5 v/v): Rf 0.59. 1H NMR (DMSO-d 6, 300 MHz): δ = 4.11 (s, 2 H, CH2), 7.24 (s, 1 H, H-6), 10.71 (br s, 1 H, NH), 11.05 (br s, 1 H, NH). 13C NMR (DMSO-d 6, 75.04 MHz): δ = 55.7 (CH2), 112.6 (C-5), 138.1 (C-6), 151.3 (C-2), 163.7 (C-4). 4: White powder; mp >300 °C (H2O); TLC (CHCl3-MeOH, 8:2 v/v): Rf 0.35. 1H NMR (DMSO-d 6, 300 MHz): δ = 3.51 (s, 2 H, CH2), 7.12 (br s, 2 H, NH2), 8.15 (s, 1 H, H-6), 11.18 (br s, 1 H, NH). 6: White powder; mp 170-172 °C (H2O); TLC (CHCl3-MeOH, 8.5:1.5 v/v): Rf 0.50. 1H NMR (DMSO-d 6, 300 MHz): δ = 1.36 (s, 3 H, CH3), 1.57 (s, 3 H, CH3), 3.85 (d, 1 H, J gem = 12.1 Hz, H-5′a), 3.97 (d, 1 H, J gem = 12.1 Hz, H-5′b), 4.12 (s, 1 H, CH2), 4.80 (dd, 1 H, J 3 ,4 = 3.0 Hz, J 4 ,5 = 2.4 Hz, H-4′), 4.95 (dd, 1 H, J 3 ,4 = 3.0 Hz, J 2 ,3 = 6.2 Hz, H-3′), 4.98 (brs, 1 H, OH), 5.01 (dd, 1 H, J 2 ,3 = 6.2 Hz, J 1 ,2 = 2.5 Hz, H-2′), 5.67 (d, 1 H, J 1 ,2 = 2.5 Hz, H-1′), 7.57 (s, 1 H, H-6), 9.01 (br s, 1 H, NH). 7: White foam; TLC (CHCl3-MeOH, 9.5:0.5 v/v): Rf 0.61. 1H NMR (CHCl3, 300 MHz): δ = 1.08 (s, 9 H, 3 CH3), 1.34 (s, 3 H, CH3), 1.57 (s, 3 H, CH3), 3.94 (d, 1 H, J gem = 12.4 Hz, H-5′a), 3.96 (d, 1 H, J gem = 12.4 Hz, H-5′b), 4.26 (dd, 1 H, J 3 ,4 = 3.3 Hz, J 4 ,5 = 2.6 Hz, H-4′), 4.75 (m, 1 H, H-3′), 4.82 (m, 1 H, H-2′), 5.44 (d, 1 H, J 1 ,2 = 3.1 Hz, H-1′), 5.97 (d, 1 H, J 5,6 = 5.0 Hz, H-5), 7.34-7.41 (m, 5 H, Ar-H), 7.44-7.65 (m, 6 H, Ar-H, H-6), 9.51 (br s, 1 H, NH). 13C NMR (CHCl3, 75.04 MHz): δ = 19.3 (Me3 C), 25.3 (CH3), 26.9 (Me 3 C), 27.2 (CH3), 63.9 (C-5′), 80.1 (C-3′), 84.9 (C-2′), 86.4 (C-4′), 91.5 (C-1′), 102.4 (Me2 C), 114.3 (C-5), 127.8, 127.9, 129.9, 130.0, 132.2, 132.7, 135.3, 135.5 (Ar-Carbons), 140.6 (C-6), 150.1 (C-2), 163.3 (C-4). 8: White foam; TLC (CHCl3-MeOH, 9:1 v/v): Rf 0.58. 1H NMR (CHCl3, 300 MHz): δ = 1.10 (s, 9 H, 3 CH3), 1.35 (s, 3 H, CH3), 1.60 (s, 3 H, CH3), 3.90 (d, 1 H, J gem = 12.2 Hz, H-5′a), 3.94 (d, 1 H, J gem = 12.2 Hz, H-5′b), 4.15 (s, 2 H, CH2), 4.15 (dd, 1 H, J 3 ,4 = 3.0 Hz, J 4 ,5 = 2.7 Hz, H-4′), 4.77 (dd, 1 H, J 3 ,4 = 3.0 Hz, J 2 ,3 = 6.3 Hz, H-3′), 4.80 (dd, 1 H, J 2 ,3 = 6.3 Hz, J 1 ,2 = 3.2 Hz, H-2′), 5.50 (d, 1 H, J 1 ,2 = 3.2 Hz, H-1′), 7.35-7.44 (m, 5 H, Ar-H), 7.50-7.60 (m, 5 H, Ar-H), 8.01 (s, 1 H, H-6), 10.32 (br s, 1 H, NH). 10: Pale yellow foam; TLC (CHCl3-MeOH, 9:1 v/v): Rf 0.45.
1H NMR (DMSO-d 6, 300 MHz): δ = 1.36 (s, 3 H, CH3), 1.63 (s, 3 H, CH3), 3.49 (s, 2 H, CH2), 4.01 (m, 2 H, H-5′), 4.31 (m, 1 H, H-4′), 4.39 (m, 1 H, H-3′), 4.78 (m, 1 H, H-2′), 5.51 (d, 1 H, J 1 ,2 = 2.8 Hz, H-1′), 7.21 (br s, 2 H, NH2), 8.01 (s,
1 H, H-6). 12: Yellow foam; TLC (CHCl3-MeOH, 9:1 v/v): Rf 0.65. 1H NMR (CDCl3, 300 MHz): δ = 1.37 (s, 3 H, CH3), 1.63 (s, 3 H, CH3), 3.50 (s, 2 H, CH2), 3.79 (m, 2 H, H-5′), 4.33 (m, 1 H, H-4′), 4.95 (m, 1 H, H-3′), 5.09 (m, 1 H, H-2′), 5.60 (d, 1 H, J 1 ,2 = 2.9 Hz, H-1′), 7.09-7.25 (m, 8 H, NH2, Ar-H), 7.29-7.38 (m, 9 H, Ar-H), 8.06 (s, 1 H, H-6).