腈被氯化亞錫/HCl氣體還原，形成Sn-醛亞胺絡合物，水解得到醛的反應，被稱為Stephen醛合成反應。此反應最早由Stephen在1925年首先報道。反應中生成的醛亞胺-氯化錫絡合物（RCH=NH·HCl)2SnCl4）在乙醚中不溶，直接過濾洗滌純化，然后水解得到產(chǎn)物醛。對于一些不能生成不溶性絡合物的底物腈通常反應不好。如果反應中能絡合物中間體，也可以直接水解不用事先分離。通常芳香腈的反應效果要優(yōu)于脂肪腈。此反應在強酸條件下進行，基團耐受度不是很好，實現(xiàn)由腈制備醛，通常利用在低溫下還原得到。

反應機理

HCl首先活化氰基，氯化亞錫對氰基碳進行單電子轉(zhuǎn)移，生成醛亞胺-氯化錫絡合物，水解后得到醛。

反應實例

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.

【W(wǎng)illiams, 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 Journal2002, 8(12), 2753-2763】

【W(wǎng)O2004041793 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】

相關(guān)文獻

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

參考資料

一、Comprehensive Organic Name Reactions and Reagents, by Zerong Wang，2659-2662.

二、Organic Syntheses Based On Name Reactions, 3RdEd, A. Hassner, Page 456.