[Scooby-Doo]

Chào BW-swe,

Hy vọng bạn đã điều chế được ketal từ dẫn xuất ester của sorbitol. Lâu quá Scooby-Doo mới quay lại diễn đàn nên bây giờ mới đọc câu hỏi của bạn.

Nếu bạn vẫn chưa điều chế được ketal mong muốn thì bạn có thể xem xét những yếu tố sau:

1. Dẫn xuất sorbitol dùng làm starting material (SM) còn mấy nhóm OH? Bạn muốn bảo vệ nhóm OH nào? SM của bạn có khan nước không? Nếu là chất lỏng có thể làm khan bằng MgSO4 hoặc MS 4A. Nếu là chất rắn có thể rút nước bằng bơm chân không qua đêm hoạc 1-2 ngày.

2. Có thể dùng acetone để bảo vệ được hay không? Hay phải bắt buộc phải dùng p-anisalhedyde? Nếu dùng acetone, bạn có thể làm khan acetone bằng MS 4A để làm khan qua đêm rồi tiến hành phản ứng. Dùng lượng dư acetone để làm dung môi phản ứng luôn. Nếu dùng acetone, bạn chỉ cần nhỏ vài giọt acid HCl đậm đặc rồi đun hoàn lưu từ 2-48 giờ. Nhớ theo dõi bằng TLC để xem phản ứng diễn ra thế nào. Dung môi cho TLC có thể là EtOAc nguyên chất, hay CHCl3-MeOH, hay CH2Cl2-MeOH. Có thể dung bản silica gel, không cần dùng bản alox.

3. THF bạn dùng làm khan bằng cái gì? 03 cách phổ biến nhất, Scooby-Doo đã dùng qua: Na-benzophenone, hỗn hống Na-K hay LiAlH4 đều cho kết quả tốt. Để an toàn, nên làm khan THF trước bằng KOH viên một đêm rồi hẵng cho vào bình cầu để đun hoàn lưu và chưng cất. Hoặc có thể làm như TLTK ở dưới.

4. p-Anisaldehyde có còn tinh khiết không? Có thể chạy IR hay GC hay NMR để kiểm tra xem có vết nước hay acid không? Nếu cần có thể chưng cất lại.

5. MgSO4 bạn cho vào phản ứng có thật sự khan nước hay không? Vì khí hậu ở VN rất ẩm,nên MgSO4 hút ẩm rất nhanh, nên không tốt cho phản ứng.

Thường hiệu suất bảo vệ diol bằng aldehyde cho hiệu suất từ 40-100% tùy loại chất nền và aldehyde sử dụng.

Chúc bạn thành công.

Cach lam khan THF:

Tetrahydrofuran [109-99-9] M 72.1, b 25°/176mm, 66°/760mm, dj° 0.889, n2
D° 1.4070, pK-2.48 (aq H2SO4). It is obtained commercially by catalytic hydrogenation of furan from pentosancontaining agricultural residues. It was purified by refluxing with, and distilling from LiAlI^ which removes water, peroxides, inhibitors and other impurities [Jaeger et al. J Am Chem Soc 101 717 1979]. Peroxides can also be removed by passage through a column of activated alumina, or by treatment with aq ferrous sulfate and sodium bisulfate, followed by solid KOH. In both cases, the solvent is then dried and fractionally distd from sodium. Lithium wire or vigorously stirred molten potassium have also been used for this purpose. CaH2 has also been used as a drying agent.

Several methods are available for obtaining the solvent almost anhydrous. Ware [/ Am Chem Soc 83 1296 7967] dried vigorously with sodium-potassium alloy until a characteristic blue colour was evident in the solvent at Dry-ice/cellosolve temperatures. The solvent was kept in contact with the alloy until distd for use. Worsfold and Bywater [J Chem Soc 5234 I960], after refluxing and distilling from ?2O5 and KOH, in turn, refluxed the solvent with sodium-potassium alloy and fluorenone until the green colour of the disodium salt of fluorenone was well established. [Alternatively, instead of fluorenone, benzophenone, which forms a blue ketyl, can be used.] The tetrahydrofuran was then fractionally distd, degassed and stored above CaH2- p-Cresol or hydroquinone inhibit peroxide formation. The method described by Coetzee and Chang [Pure Appl Chem 57 633 1985] for 1,4-dioxane also applies here. Distns should always be done in the presence of a reducing agent, e.g. FeSO4. It irritates the skin, eyes and mucous membranes and the vapour should never be inhaled. It is HIGHLY FLAMMABLE and the necessary precautions should be taken.
Rapid purification: Purification as for diethyl ether.

Cach lam khan Diethyl ether:
Diethyl ether (ethyl ether) [60-29-7] M 74.1, b 34.6°/760mm, d 0.714, n15 1.3555, n
1,35272. Usual impurities are water, EtOH, diethyl peroxide (which is explosive when concentrated), and aldehydes. Peroxides [detected by liberation of iodine from weakly acid (HCl) solutions of KI, or by the blue colour in the ether layer when lmg of Na2Cr2Oy and 1 drop of dil H2SO4 in ImL of water is shaken with 1OmL of ether] can be removed in several different ways. The simplest method is to pass dry ether through a column of activated alumina (8Og Al2O3/700mL of ether). More commonly, IL of ether is shaken repeatedly with 5-
1OmL of a soln comprising 6.Og of ferrous sulfate and 6mL of cone H2SO4 in 11OmL of water. Aqueous 10% №2803 or stannous chloride can also be used. The ether is then washed with water, dried for 24h with CaCl2, filtered and dried further by adding sodium wire until it remains bright. The ether is stored in a dark cool place,until distd from sodium before use. Peroxides can also be removed by wetting the ether with a little water, then adding excess LiAlH4 or CaH2 and leaving to stand for several hours. (This also dried the ether.)

Werner [Analyst 58 335 1933] removed peroxides and aldehydes by adding 8g AgNO3 in 6OmL of water to IL of ether, then 10OmL of 4% NaOH and shaking for 6min. Fierz-David [Chimia 1 246 1947} shook IL of ether with 1Og of a zinc-copper couple. (This reagent was prepared by suspending zinc dust in 5OmL of hot water, adding 5mL of 2M HCl and decanting after 20sec, washing twice with water, covering with 5OmL of water and 5mL of 5% cuprous sulfate with swirling. The liquid was decanted and discarded, and the residue was washed three times with 2OmL of ethanol and twice with 2OmL of diethyl ether).

Aldehydes can be removed from diethyl ether by distn from hydrazine hydrogen sulfate, phenyl hydrazine or thiosemicarbazide. Peroxides and oxidisable impurities have also been removed by shaking with strongly alkaline satd KMnO4 (with which the ether was left to stand in contact for 24h), followed by washing with water, cone H2SO4, water again, then drying (CaC^) and distn from sodium, or sodium containing benzophenone to form the ketyl. Other purification procedures include distn from sodium triphenylmethide or butyl magnesium bromide, and drying with solid NaOH or P2O5. Rapid purification: Same as for 1,4-dioxane.

TLTK: PURIFICATION OF LABORATORY CHEMICALS, F i f t h E d i t i o n
Wilfred L. E Armarego, Christina Li Lin Chai