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

Adel A.-H.  Abdel-Rahman; El S. H.  El Ashry

doi:10.1055/s-2002-35592

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Synlett 2002(12): 2043-2044
DOI: 10.1055/s-2002-35592

LETTER

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

Adel A.-H. Abdel-Rahman^a, 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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Publication History

Received 1 October 2002
Publication Date:
20 November 2002 (online)

Abstract
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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.

Key words

microwave - uracil - cytosine - 5-hydroxymethyluracil - uridine - cytidine - formaldehyde addition

References

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20

Selected Physical Data: 2: White powder; mp >300 °C (H₂O); TLC (CHCl₃-MeOH, 8.5:1.5 v/v): R_f 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): R_f 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): R_f 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): R_f 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 ₃C), 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): R_f 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): R_f 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): R_f 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).