5-(Hydroxymethyl)uracil

5-Hydroxymethyluracil is a product of oxidative DNA damage. 5-Hydroxymethyluracil can be used as a potential epigenetic mark enhancing or inhibiting transcription with bacterial RNA polymerase.

Solid

5-hydroxymethyluracil is a primary alcohol that is uracil bearing a hydroxymethyl substituent at the 5-position. It has a role as a human metabolite. It is a primary alcohol and a pyrimidone. It derives from a uracil.

To a mixture of 1H-pyrimidine-2, 4-dione (20 g, 178.4 mmol) in aqueous solution of potassium hydroxide (8.0 g, 142.7 mmol) in water (160.0 mL), paraformaldehyde (6.96 g, 231.9 mmol) was added portion-wise at 0° C. The resulting reaction mixture was stirred at 55° C. for 36 h. After completion, the reaction was cooled to room temperature and concentrated to A suspension of uracil (2.5 g, 22.3 mmol) and para-formaldehyde (2.0 g, 66.9 mmol) in H2O (75 mL)was treated with NEt3 (4.6 mL, 33.4 mmol) and heated with stirring at 60 °C for 16 h. The mixture wasrotary evaporated, and the residue triturated with H2O and EtOH (1:1, 20 mL), stirred for 1 h at 0 °C, filtered and washed with cold EtOH to yield 5-hydroxymethyluracil (20) (2.3 g, 73 percent) as a white solidA mixture of uracil (3.6 g, 32.1 mmol), formaldehyde (37percent in water) (3.25 ml), KOH (1.4 g, 25 mmol) in water (45 ml) was stirred at 50° C. for 20 h. The reaction was acidified with 1 N HCl to give a white precipitate. The solids were collected dried under vacuum to give the 5-(hydroxymethyl)-2, 4(1H, 3H)-pyrimidinedione (2.01 g, 44percent) as a white solid.Uracil (10.0 g, 89.2 mmol, 1.0 eq.) and paraformaldehyde (3.24 g, 107 mmol, 1.2 eq.) were treated with KOH (0.5 M, 133 ml) and the mixture heated at 50 °C for 8 hours 30 minutes, stirred at rt for 64 hours then heated at 50°C for 24 hours. The mixture was cooled to 0°C in an ice bath and acidified to pH 6 with HC1 (conc). The precipitate wasfiltered off, washed with water and oven dried providing the title compound (4.93 g, 39percent) as a white solid.‘HNMR (400 MHz, DMSO)6 11.05 (s, IH), 10.71 (s, 1H), 7.24(s, IH), 4.85 (t, J=5.5 Hz, 1H), 4.11 (dd, J 5.5, 1.1 Hz, 2H). Rf = 0.10 (50:8:1 DCM:EtOH:NH3)Intermediate 1 [00353j A 1-L, three-necked flask equipped with a mechanical stirrer, was charged with uracil (45.0 g, 401 mmol) and paraformaldehyde (14.5 g, 483 mmol). A solution of potassium hydroxide (0.5 M, 600 mL, 0.30 mol) was added in one portion. The resulting mixture was stirred at 55 °C overnight. The mixture was cooled in an ice-water bath and the pH was adjusted to 6 with 12 N HC1. The resulting precipitate was collected by filtration and dried to afford the title compound (46.0 g) as a white solid which was used in the next step without further purification. ‘H NMR (400 MHz, DMSO-d6): ö 4.12 (d, 2H), 4.78 (t, 1H), 7.24 (s, 1H), 10.64 (s, 1H), 10.98 (s, 1H).(2) Uracil (13.5 g, 100 mmol) and paraformaldehyde (4.5 g, 120 mmol) were dissolved in 150 mL of 0.5 mol / L After the potassium hydroxide solution was stirred for half an hour, it was stirred in a water bath at 52 ° C for about 20 hours. The thin layer analysis showed that the raw material completely disappeared. Most of the water is removed with a rotary evaporator so that the inner volume of the flask is approximately 1/3 of the original volume, After adding an equal amount of acetone recrystallized at 0 ~ 5 °C , 3 hours, suction filtration, washing, pumping dry, vacuum drying, weighing. Product is a white solid 16.26g

Molecular Weight:142.11
XLogP3:-1.9
Hydrogen Bond Donor Count:3
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:1
Exact Mass:142.03784206
Monoisotopic Mass:142.03784206
Topological Polar Surface Area:78.4
Heavy Atom Count:10
Complexity:209
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes