Preparation of Cyclic Sulfites by Transesterification of Diols and Diisopropyl Sulfite

Abstract

Cyclic Sulfites of 1,2-, 1,3- and 1,4-diols can be prepared in high yield by acid or base catalyzed transesterification with diisopropyl sulfite.

Notes

Diisopropyl Sulfite: Toluene (500 mL) and isopropanol (240 g, 306 mL, 4.00 mol) were combined under nitrogen in a 2 L flask equipped with a dropping funnel. Thionyl chloride (119 g, 73 mL, 1.00 mol) was added from the dropping funnel over 30 min maintaining the reaction temperature at 15–25°C. Some HCl evolution is noted as the reaction proceeds. When the addition was complete, the reaction mixture is put under vacuum to remove HCl. The pressure is slowly lowered. When gas evolution ceases the mixture is concentrated to remove toluene and excess isopropanol. The yield is 157 g (95%). Triethylamine (1 mL) is added to remove residual HCl and the incipient precipitate is filtered away.

Acid Catalyzed Transesterification - Typical Procedure: 1,4-Butanediol (10.1 g, 112 mmol) was suspended in toluene (300 mL) and DIS (19.4 g, 117 mmol). Methanesulfonic acid (0.07 mL, 1.1 mmol) was added and the mixture was distilled at 50°C/95 torr. After 100 mL was collected, the reaction was complete and several drops of triethylamine were added to neutralize the catalyst. The solvent was removed and the product was distilled at 80° C/3 torr to yield 13.0 g (85%) of 12 as a clear liquid. NMR data for the cyclic sulfites (compounds 2, 8–12), taken in CDCl₃ using a 250 MHz instrument are given as follows in δ (ppm):

2) ¹H-NMR: 5.24 (d, J=11.2 Hz, 2H), 3.04 (d, J=11.7 Hz, 2H), 0.84 (dd, J=8.0 6.8 Hz, 2H), 0.47 (dd, J=8.8, 6.6 Hz, 2H). ¹³C-NMR: 64.7, 18.0, 12.9, 7.0.

8) ¹H-NMR: 4.89 (m, 2H), 3.82 (m, 2H), 2.49 (m, 1H), 1.61 (m, 1H). ¹³C-NMR: 57.3, 25.9.

9) ¹H-NMR: 4.59 (d, J=11 Hz, 2H), 3.38 (d, J=11 Hz, 2H), 1.27 (s, 3H), 0.83 (s, 3H). ¹³C-NMR: 66.4, 31.6, 22.5, 22.4).

10) diasteromer A: ¹H-NMR: 7.40 (m, 5H), 5.92 (t, J=6.9 Hz, 1H), 4.93 (dd, J=8.5, 6.5 Hz, 1H), 4.19 (dd, J=8.5, 7.4 Hz, 1H). ¹H-NMR: diasteromer B: 7.40 (m, 5H), 5.41 (dd, J=10.6, 6.5 Hz, 1H), 4.74 (dd, J=9.2, 6.5 Hz, 1H), 4.46 (dd, J=10.6, 9.2 Hz, 1H). ¹³C-NMR for diastereomers A and B: 134.5, 133.9, 129.6, 129.5, 129.1, 127.6, 126.7, 85.6, 81.0, 73.6, 71.4.

11) ¹H-NMR: 7.39 (m, 8H), 7.25 (m, 2H), 5.71 (d, J=9.8 Hz, 1H), 5.23 (d, J=9.8 Hz, 1H). ¹³C-NMR: 133.3, 132.2, 129.7, 129.4, 129.0, 127.6, 127.2, 91.3, 86.0.

12) ¹H-NMR: 4.45 (m, 2H), 3.95 (M, 2H), 1.82 (m, 4H). ¹³C-NMR: 64.1, 28.3.

Base Catalyzed Transesterification and Sulfite Displacement: A solution of 1,1-bis(hydroxymethyl)cyclopropane (25.5 g, 250 mmol) in DMF (250 mL) was prepared and 25 mL was distilled at 70°C/50 torr to dry the solution. NaOrBu solution (2M in THF, 2.0 mL, 4.0 mmol) was added and isopropanol was removed by vacuum distillation (35 - 70°C/50 torr). The base catalyst slowly decomposed during the reaction, so a NaOtBu solution (1.0 mL, 2.0 mmol) was added and the distillation was continued until GC assay showed that less than 0.5 % diol remained and ¹H-NMR showed that less than 2 mol% IPA remained in the reaction mixture. When the mixture had cooled to room temperature, NaCN (13.5 g, 275 mmol) and NaI (7.5 g, 50 mmol) was added. The heterogeneous mixture was slowly warmed over 1 h to 70°C and aged with vigorous stirring. The reaction was followed by GC and was stopped after 36 h when there was less than 2% cyclic sulfite 2 remaining. The reaction was worked up by adding toluene (400 mL) slowly at 70°C. Water (6 mL) was then added dropwise over 30 min. The water addition causes precipitation of large amounts of light yellow solid which was filtered away. The product 7 was obtained as a solution in 77% (21.4 g by GC assay) yield from diol 1. For 7: ¹H-NMR (CDCl₃, 250 MHz) δ (ppm): 3.54 (s, 2H), 2.57 (s, 2H), 0.63 (m, 4H); ¹³C-NMR (CDCl₃, 62 MHz) δ (ppm): 118.6, 67.3, 22.5, 19.3, 9.8.