Rutile Promoted Synthesis of Sulfonylamidonitriles from Simple Aldehydes and Sulfonamides

Abstract

We report the first rutile-promoted synthesis of sulfonylamidonitriles from aldehydes and sulfonamides with NaCN in water. This transformation has proven to work for a variety of aliphatic and aromatic aldehydes with excellent yields. The scope also extends to a variety of substituted sulfonamides. Rutile can be easily recycled and reused without significant reaction erosion. The benign nature of rutile and its natural abundance highlights this transformation as a model green reaction.

Mechanochemical Strecker Reaction: Access to α‐Aminonitriles and Tetrahydroisoquinolines under Ball‐Milling Conditions

“…Once again, the milling of the three components in the presence of SiO 2 gave the corresponding α‐aminonitriles 8 a – d in yields ranging from 70 to 95 %. In addition, the more challenging p ‐toluenesulfonamide ( 5 f ) was utilized as amino component . After three hours of milling, sulfonylamidonitrile 8 e was obtained in 45 %.…”

“…In addition, the more challenging p-toluenesulfonamide (5f)w as utilized as amino component. [17] After three hours of milling, [a] Reactionc onditions: 1a-l (0.5 mmol), 5a (53.6 mg, 0.5 mmol), KCN (35.8 mg, 0.55 mmol), and SiO 2 (240 mg) were milled in ap lanetary ball mill at 700 rpm for 3h using a1 2mLa gate jar with 20 agate balls of 5mmi nd iameter. sulfonylamidonitrile 8e was obtained in 45 %.…”

Strecker-Derived Methodology for Library Synthesis of N-Acylated α-Aminonitriles

“…In addition, limited documentation can be found in the literature for a related reaction type involving the use of sulfonamides. 17 The under-representation of such reactions in the literature is likely to be related to the reduced nucleophilicity of acylated amines, implying a more sluggish formation of the N -acylimine intermediate of the reaction. Likewise, the relatively higher Gibbs free energy of an N -acylimine intermediate (compared to a classical imine) also contributes to the inherently lower reactivity of acylated amines in Strecker settings.…”

“…To the best of our knowledge, however, the same direct condensation involving a carboxamide instead of a carbamate has not been reported. In addition, limited documentation can be found in the literature for a related reaction type involving the use of sulfonamides . The under-representation of such reactions in the literature is likely to be related to the reduced nucleophilicity of acylated amines, implying a more sluggish formation of the N -acylimine intermediate of the reaction.…”

Synthesis and Biological Activity Study of Novel Cyano-containing Multi-substituted Pyrazoles Obtained via Strecker Reaction

“…通过 Strecker 反应, 醛(或酮)、胺、HCN 三组分可 一步合成 α-氨基腈 [1] , 该类物质不仅是制备氨基酸的重 要原料 [2] , 而且是构建多种重要有机分子骨架的关键中 间体 [3] ; 此反应可广泛用于氨基酸 [4] 、同位素标记物 [5] 、 天然产物 [6] 、药物 [7] 及农药合成 [8] 等领域, 以及生命起源 等基本科学问题的研究 [9] . 近年来大量报道表明, MgI 2 乙醚加合物 [10] 、Zn(OAc) 2 [11] 、ZnCl 2 氯化胆碱加合物 [12] 、 Sc(III) [13] 、In(III)和 Ga(III)盐 [14] 、V(V)配合物 [15] 、金红 石(TiO 2 )及二茂钛衍生物 [16,17] 、ZrOCl 2 [18] 、HfCl 4 [19] 、硫 酸钼(MSA) [20] 、Fe(II)配合物 [21] 、杂多酸 [22] 等金属离子 催化剂, 及甲酸 [23] 、NH 4 Cl [24] 、离子液体 [25] 、石墨烯 [26] 、 氮卡宾 [27] 、木质素 [28] 、壳聚糖 [29] 等非金属催化剂对反应 都有催化作用, 多孔骨架催化剂 [30] 和改性固载催化 剂 [31] 的研究则是以实现反应的绿色化为目标, 对烷基 亚磺酰胺 [32] 、糖 [33] 、手性胺 [34] 等手性辅体和联萘 [35] 、 奎宁 [36] 、(硫)脲 [37] 、binol 催化剂 [38] 、膦配合物 [39] 、方酮 衍生物 [40] 、金刚烷衍生物 [41] 、环胍衍生物 [42] 、糖 [43] 、 双磺酸配合物 [44] 、改性共聚物 [45] 等催化剂的研究, 则以 实现反应的高效立体选择性为目标; 除常用的 TMSCN 外, 2-氰基-2-丙醇 [46] 、氰基乙酰 [47] 、六氰合铁(II)酸钾 [48] 等低毒氰化物也可作为反应氰源. 然而, 在现有报道中, 该反应的胺底物多为取代苯胺或脂肪胺、环状亚胺, 而 杂环芳胺作为底物的研究鲜见报道.…”