A Mild Synthesis of ¹³C-Methanol

Abstract

The formation of oxazolidinon-2-ones from amino alcohols and carbon dioxide is well known. Until now it was not possible to reduce the fixed carbon dioxide to any basic chemical like formaldehyde or methanol, only the less interesting N-methyl compounds were formed with lithium aluminium hydride. Here we show the reduction of a oxazolidin-2-one derivative to methanol and the corresponding sulfone amide after introducing a sulfone group at the nitrogen. With selective labelling of the carbonyl ­carbon it was possible to produce ¹³C-labelled methanol.

carbon dioxide - sulfonation - reduction - oxazolidin-2-ones - methanol

References

1 Inui T. In Effective Conversion of CO ₂ to Valuable Compounds by Using Multifunctional Catalysts   Song C. Gaffney AF. Fujimoto K. ACS Symposium Series 809; Washington DC: 2002.  p.153 

2 Arakawa H. Aresta M. Armor JN. Barteau MA. Beckman EJ. Bell AT. Bercaw JE. Creutz C. Dinjus E. Dixon DA. Domen K. DuBois DL. Eckert J. Fujita E. Gibson DH. Goddard WA. Goodman DW. Keller J. Kubas GJ. Kung HH. Lyons JE. Manzer LE. Marks TJ. Morokuma K. Nicholas KM. Periana R. Que L. Rostrup-Nielson J. Sachtler WMH. Schmidt LD. Sen A. Somorjai GA. Stair PC. Stults BR. Tumas W. Chem. Rev.  2001,  101:  953 

3 Suda T. Iwaki T. Mimura T. Chem. Lett.  1996,  25:  777 

4a Hassner A. Burke SS. Tetrahedron  1974,  30:  2613 

4b Schlörer E. PhD Thesis   Universität Leipzig; Germany: 2001. 

5 Tominaga K. Sasaki Y. Synlett  2002,  307 

6

We are indepted to Prof. K. Burger and Prof. H. Wilde (University Leipzig) for helpful suggestions.

7

Sulfonation of Oxazolidin-2-one ( 5). Oxazolidin-2-one (500 mg, 3.07 mmol) was dissolved in dry THF (10 mL) under N₂ atmosphere. At -80 °C n-BuLi (1.93 mL, 3.07 mmol, 1.6 M solution in THF) was added slowly to the solution. After the solution was allowed to warm up to -30 °C, p-toluenesulfonyl chloride (585 mg, 3.07 mmol) in dry THF (5 mL) was added. After stirring at r.t. for 4 h, the reaction mixture was hydrolyzed with sat. NH₄Cl solution, extracted with EtOAc (4 × 20 mL), the organic layer was dried (MgSO₄) and the solvent evaporated. The residue was recrystallized from EtOH to yield the N-sulfonated oxazolidin-2-one (6b, 836 mg, 86%); mp 122-124 °C. ¹H NMR (400 MHz, CDCl₃, TMS): δ = 2.47 (s, Ph-CH ₃), 3.89 (dd, ² J _HH = 9.2 Hz, ³ J _HH = 7.8 Hz, CH _A -NH), 4.42 (dd, ² J _HH = 9.2 Hz, ³ J _HH = 8.1 Hz, CH _B -NH), 5.52 (dd, ³ J _HH = 8.1 Hz, O-CH), 7.37 (m, Ph), 7.95 (d, ³ J _HH = 8.1 Hz, Ph). ¹³C NMR (100 MHz, CDCl₃, TMS): δ = 21.7 (Ph-CH₃), 51.6 (CH₂-N), 75.3 (Ph-CH), 125.6, 128.3, 128.9, 129.1, 133.8, 136.2, 145.7 (Ph), 151.5 (C=O). MS (ES⁺): m/z = 318 [M⁺].

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Reduction of Sulfonated Oxazolidin-2-one ( 6b) Under an N₂ atmosphere, LiAlH₄ (15 mg, 0.39 mmol) was dissolved in dry THF (5 mL). While cooling the suspension (0 °C), the N-tosyloxazolidin-2-one (200 mg, 0.63 mmol) in THF (5 mL) was added slowly and refluxed for 2 h. After cooling to r.t. the mixture was hydrolyzed with sat. NH₄Cl solution, extracted with Et₂O (4 × 15 mL) and the solvent removed to yield the sulfone amide 7b (149 mg, 81%); mp 115-117 °C.
¹H NMR (400 MHz, CDCl₃, TMS): δ = 2.42 (s, Ph-CH ₃), 3.03 (dd, ² J _HH = 13.4 Hz, ³ J _HH = 8.5 Hz, CH _A -NH), 3.85 (dd, ² J _HH = 13.4 Hz, ³ J _HH = 3.5 Hz, CH _B -NH), 4.80 (dd, ³ J _HH = 8.5 Hz = 3.5 Hz, CH-Ph), 7.29 (m, Ph), 7.72 (d, ³ J _HH = 8.1 Hz, Ph). ¹³C NMR (100 MHz, CDCl₃, TMS): δ = 21.5 (Ph-CH₃), 50.2 (CH₂-NH), 72.8 (CH-Ph), 125.8, 127.1, 128.3, 128.7, 129.8, 136.8, 140.8 and 143.6 (Ph). MS (ES⁺): m/z = 292 [M]⁺.

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Determination of the Yield of Methanol in the Unlabelled Case.
The reaction was performed like described (200 mg, 0.63 mmol 6b). After hydrolysis the reaction mixture was filtered off and filled with H₂O to a volume of 10 mL. An aliquot (0.5 mL) was taken and a ¹H NMR spectrum was measured. As integral reference we used sodium benzoate (453.5 mg in 10 mL H₂O), because of its good solubility and the well separated ortho-protons of the aromatic ring. Then, 200 µL of a standard solution were added and the integrals of the methyl group signals of the methanol and the ortho-proton signals of the benzoate were compared to find a methanol yield of 73% (0.46 mmol).

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