腈被氯化亚锡/HCl气体还原，形成Sn-醛亚胺络合物，水解得到醛的反应，被称为Stephen醛合成反应。此反应最早由Stephen在1925年首先报道。反应中生成的醛亚胺-氯化锡络合物（RCH=NH·HCl)2SnCl4）在乙醚中不溶，直接过滤洗涤纯化，然后水解得到产物醛。对于一些不能生成不溶性络合物的底物腈通常反应不好。如果反应中能络合物中间体，也可以直接水解不用事先分离。通常芳香腈的反应效果要优于脂肪腈。此反应在强酸条件下进行，基团耐受度不是很好，实现由腈制备醛，通常利用DIBALH在低温下还原得到。
反应机理
HCl首先活化氰基，氯化亚锡对氰基碳进行单电子转移，生成醛亚胺-氯化锡络合物，水解后得到醛。
反应实例
Phenylacetaldehyde (7). Dry HCl gas was passed for 2 h with stirring into anhyd SnCl2 (57 g, 0.3 mol in 400 mL dry ether) to form a separate viscous layer. Freshly distilled 6 (16 g, 0.136 mol) was added with vigorous stirring for 1 h. After the mixture stood for 18 h, 2 slowly separated and after 5 h the ether was decanted and the residue washed with dry ether. Water (800 mL) and NaHCO3 (till neutral to congo red) were added to the residue. The mixture was boiled and steam was passed through until the total volume of distillate was 250 mL. Extraction with ether and workup afforded 5.4 g, 33% of 7, bp 87–88 C.
【Williams, J. W., J. Am. Chem. Soc., 1939, 61, 2248】
【J. Am. Chem. Soc., 1949, 71, 2862】
【Russian Journal of General Chemistry (Translation of Zhurnal Obshchei Khimii) ，2001, 71(7), 1121-1125】
【Chemistry - A European Journal 2002, 8(12), 2753-2763】
【WO2004041793 A1】
【Russian Journal of Organic Chemistry，2006, 42, 430–434】
To a solution of anhydrous diethyl ether (100 mL), anhydrous stannous chloride (37.9 g, 0.2 mol) and acetyl chloride (62.8 g, 0.8 mol) at –10 oC was added deuterium oxide (15 g, 0.75 mol) slowly dropwise such that the temperature did not rise above 10 °C. To the homogeneous solution was added benzonitrile (10.3 g, 0.1 mol), and stirring was continued for 12 h at room temperature. The precipitated crystalline stannic chloride complex was filtered away from the solution, washed with ether, dried in the dark. Hydrolysis of the complex to benzaldehyde-D was accomplished upon addition to hot water. Then the aqueous layer was extracted with EA for three times, the combined organic layers were dried and concentrated under reduced pressure, the residue was purified by column chromatography to furnish the Benzaldehyde-d (8.56 g, 80% yield). 1H NMR (300 MHz, CDCl3): δ 7.91-7.88 (m, 2H), 7.67-7.61 (m, 1H), 7.57-7.51 (m, 2H).
【J. Am. Chem. Soc. 2021, 143, 6, 2608–2619】
相关文献
1 Stephen J J Chem Soc 1925 127 1874
2 Williams JW J Am Chem Soc 1939 61 2248
3 Ferguson LW Chem Rev 1946 38 243
4 Mosettig E Org React 1954 8 246
5 Stephen TW J Chem Soc 1956 4695
6 Tolbert J J Org Chem 1963 28 696
7 Markaryan EA Armen Khim Zhu 1974 27 878
8 Voloboev SN Russ J Gen Chem 2001 71 1121
参考资料
一、Comprehensive Organic Name Reactions and Reagents, by Zerong Wang，2659-2662.
二、Organic Syntheses Based On Name Reactions, 3RdEd, A. Hassner, Page 456.
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