α‐Cyanation of Aromatic Tertiary Amines using Ferricyanide as a Non‐Toxic Cyanide Source

Abstract

Ther eactiono fa romatic tertiary amines with potassium ferricyanide directly providest he useful a-amino nitriles.T he inexpensive iron complex functionsb oth as an oxidant anda sacyanide source.T he presence of molecular oxygen speeds up the reactionw hich can be performed in aqueous tert-butanol or even in ethanol-based mixturesl ike Te quila. While amine cyanations usually employ highly toxic cyanide sources,p otassium ferricyanide is evenl ess toxic than table salt.N oe xpensive metal complexes are requireda sc atalysts and the co-product of the cyanation, Prussian blue,h as no known toxicity and is ratherused as an antidote.

Mechanochemical Activation of Iron Cyano Complexes: A Prebiotic Impact Scenario for the Synthesis of α‐Amino Acid Derivatives

“…Various aromatic and aliphatic aldehydes reacted with benzylamine ( 2 a ) and K 3 [Fe(CN) 6 ] affording the expected products 3 aa – 3 ia in good yields. Using benzaldehyde ( 1 a ) and aniline ( 2 b ) led to α‐aminonitrile 3 ab in 61 % yield, confirming the assumption that the process involved a cyanide‐imine addition and not an oxidative α‐cyanation of the amine component …”

Oxidation of Trialkylamines by BrCCl3: Scope, Applications and Mechanistic Aspects

“…In all cases, the expected α‐aminonitrile 4 was obtained in excellent yields. Alternatively, compound 4 was obtained by replacing KCN with potassium ferricyanide K 3 [Fe(CN) 6 ], a nontoxic cyanide source (see the Supporting Information) …”

Mechanochemical Activation of Iron Cyano Complexes: A Prebiotic Impact Scenario for the Synthesis of α‐Amino Acid Derivatives

“…[24] With the aim to stay as close as possible to early Earth conditions,m echanochemistry was also set into the focus for the transformation of a-aminonitriles 3 into amino acid derivatives.T he initial attempts targeted the development of ball milling methods for basic hydrations with urea-hydrogen peroxide complex (UHP). [24] With the aim to stay as close as possible to early Earth conditions,m echanochemistry was also set into the focus for the transformation of a-aminonitriles 3 into amino acid derivatives.T he initial attempts targeted the development of ball milling methods for basic hydrations with urea-hydrogen peroxide complex (UHP).…”

“…Va rious aromatic and aliphatic aldehydes reacted with benzylamine (2a)a nd K 3 [Fe(CN) 6 ]a ffording the expected products 3aa-3ia in good yields.U sing benzaldehyde (1a) and aniline (2b)l ed to a-aminonitrile 3ab in 61 %y ield, confirming the assumption that the process involved ac yanide-imine addition and not an oxidative a-cyanation of the amine component. [24] With the aim to stay as close as possible to early Earth conditions,m echanochemistry was also set into the focus for the transformation of a-aminonitriles 3 into amino acid derivatives.T he initial attempts targeted the development of ball milling methods for basic hydrations with urea-hydrogen peroxide complex (UHP). However,n either the use of substoichiometric amounts of inorganic NaOH monohydrate nor applying 1,8-diazabicyclo [5.4.0]undec-7-ene (DBU) as organic base led to satisfying results.Ineach case,the yields of amino amide 5aa were low (10-43 %) and dehydrocyanation of 3aaled to significant amounts of imine 4aa (for details,see Supporting Information).…”