2-C-Methyl-D-ribono-1,4-lactone

2-C-Methyl-D-ribono-1,4-lactone is White to Off-White Solid

D-Glucose (90.1 g) was suspended in absolute ethanol (130 mL) with acetic acid (30.0 g) and was charged to a reactor at 20 0C. Dimethylamine solution (33percent solution in absolute ethanol, 69.7 g) was added to the suspension within 30 minutes at 20 0C (exothermic), and a dropping funnel employed for additions to the reactor was rinsed with absolute ethanol (5 mL). The reaction mixture was heated to 75 0C. within a 30 minute period, then cooled to 55 0C. within 1 hour, and maintained at 55 0C. for an additional 2 hours, to afford a orange solution. The orange solution then was concentrated at 50 0C. in vacuo to provide a brown oil. Water (190 g) was then added to the brown oil, and the reactor was evacuated three times to approximately 100 mbar and each time was relieved with nitrogen, following which a weak nitrogen flow was continued. Calcium oxide (36.5 g) was added in 4 portions at 10 minute intervals at15 0C, with rises of approximately 5 0C. in internal temperature observed after addition of each portion. The reactor was evacuated twice to approximately 100 mbar and relieved with nitrogen, following which a weak nitrogen flow was continued. The mixture then was heated to an internal temperature of 25 0C within about 20 minutes, then heated to an internal temperature of 40 0C. within 18 hours, following which it was stirred at an internal temperature of 40 0C for four hours, and finally cooled to an internal temperature of 3 0C. 96percent sulfuric acid (80.6 g) was added over a 2 hour period while maintaining an internal temperature of 3 0C to provide a yellow colored mixture. The pH was checked to reach a targeted pH of between 2.4 and 2.7; EPO D-Glucose (3.17 g, 17.6 mmol) was suspended in ethanol (5 niL) with glacial acetic acid (1 niL). Dimethylamine solution (33percent solution in methylated spirits, 3.2 mL, 18.0 mmol) was added to the suspension and the reaction mixture stirred at 80 0C for one and a half hours. The resulting dark orange solution was concentrated in vacuo to afford a crude dark orange-brown oil (6.55 g). The crude product mixture was then dissolved in water (150 mL) and stirred at 70 0C with calcium oxide (5.6fg, 100 mmol) for 24 hours when TLC analysis (chloroform:methanol:water:acetic acid, 60:30:5:3) revealed no starting materials (Rf 0.09 0.24) and only baseline products. LRMS analysis (ESI -ve) of the crude alkaline reaction mixture showed only one major peak at 179.01 Da. Oxalic acid dihydrate (6.74 g, 53.5 mmol) was added to the suspension to afford a pale pink precipitate suspended in a solution with a measured pH of 10. The mixture was allowed to cool to room temperature, filtered through a pad of Celite.(R). with water and the filtrate passed through Amberlite.(R). IR 120 ion exchange resin, using water as eluent. The water was then removed under reduced pressure to afford a crude orange oil (2.39 g). The crude product was dissolved in water (50 mL) and heated at 40 0C for 15 minutes. TLC analysis (15percent methanol in dichloromethane) revealed the presence of one major product (Rf 0.38) and LRMS analysis (ESI -ve) revealed no peak at 179.01 Da and a major peak at 161.15 Da. The water was removed under reduced pressure and the crude product purified by flash column chromatography (ethyl acetate: cyclohexane, (1:1) --> ethyl acetate) and subsequently by recrystallisation from ethyl acetate by the addition of cyclohexane to afford 2-C-methyl-D-ribono-l, 4-lactone (534 mg, 19percent) as a white crystalline solid; mp 158-159 0C {Lit. 160-161 0C); [alpha]^5 +87.5 (c 0.76 in water) {Lit. [alpha.pound.° +93 (water)}; vmax(film): 3356 (br, O-H), 1773 (gamma-lactone C=O) cm4; deltaH (CD3OD, 400 EPO Starting material 3 (5.0 g, 30.84 mmol) [prepared according to Tetrahedron: Asymmetry 2007, 18, 500-512] was dissolved in anhydrous DMF (200 mL).Protected with nitrogen and cooled to -10 ° C, Slowly add 60percent NaH (1.6 g, 40.09 mmol), After stirring at -10 ° C for 1 hour, 2-Bromomethylnaphthalene (10.2 g, 46.26 mmol) was slowly added.After stirring for another 30 minutes, Add 60percent NaH (1.6g, 40.09mmol) as above.And 2-bromomethylnaphthalene (10.2 g, 46.26 mmol), Repeat twice, keep the temperature at -10 ° C and stir the reaction for 48 hours.The reaction mixture was poured into 500 mL of ice water to quench the reaction, and extracted with ethyl acetate (100 mL×4).The organic layer was washed with 200 mL of brine, dried over anhydrous sodium sulfateOn a silica column (10: 1, V / V, petroleum ether: EtOAc) to give a white oily product 3-1a (12.6g, 21.59mmol), Yield: 70percent.

Used in synthesis of enantiomerically pure 4-substituted riboses; also for preparing saccharinic acids and lactones via Amadori rearrangement for use as synthons toward herbicidal esters and branched nucleosides.

Molecular Weight:162.14
XLogP3:-1.2
Hydrogen Bond Donor Count:3
Hydrogen Bond Acceptor Count:5
Rotatable Bond Count:1
Exact Mass:162.05282342
Monoisotopic Mass:162.05282342
Topological Polar Surface Area:87
Heavy Atom Count:11
Complexity:180
Defined Atom Stereocenter Count:3
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes