Facile Conversion of Aryl Amines Having No α-Methylene to Aryl Nitriles.

Dimethyl carbonimidodithioates, 2 derived from various primary aryl amines (1) by reacting with carbon disulfide and methyl iodide in dimethyl formamide in the presence of concentrated sodium hydroxide, are converted to the diaziridine derivatives, 3 by reacting with hydrazine in ethanol. The diaziridines, 3 on oxidation with lead tetraacetate in refluxing xylene, extrudes nitrogen, and intramolecular stabilization, particularly 1,2-carbon migration, takes place to give the product, 5. The reaction may take place through the intermediates, diazirines, 4, which have not been isolated. This work provides a new approach for the conversion of aryl amines having no α-methylene to aryl nitriles.

Introduction

Nitriles are useful organic molecules found in natural products and in synthetic organic chemistry. They are used for the synthesis of a wide variety of biologically active compounds.[1] Conventionally, they are prepared from alcohols,[2] aldehydes,[2a,3] and amines[4] by the nucleophilic displacement of substrates. Other traditional methods include dehydration of amides[5] and aldoximes,[6] conversion of methyl arenes,[7] carboxylic acids,[8] and amines,[4f−4j] and the classic Sandmeyer reaction using NaNO2/HCl/CuCN to nitriles. These methods were of low atom economy, produced stoichiometric wastes, required toxic reagents, had limited selectivity, and often required drastic reaction conditions.[9]

For the transformation of primary amines to nitriles, a number of oxidations using stoichiometric metal oxidants such as KI/I2,[2e] Cu/nitroxyl,[4a] Ir,[4c] nanocatalysts,[10] OsO4,[11] TiO2,[12] nickel peroxide,[13] Nb2O5,[14] Au–Pd/ZrO2,[15] RuO2·xH2O/TiO2,[16] and copper reagents in combination with oxygen,[17] silver reagents,[18] cobalt peroxide,[19] lead tetraacetates (LTAs),[20] NiSO4/K2S2O8,[21] RuCl3/O2,[22] RuCl3/K2S2O8[23] ruthenium complex/O2,[24] Ru supported on alumina/O2,[25] molecular oxygen in the presence of transition-metal catalysts,[26,27] and so forth have been reported. Recently, use of various catalysts for oxidation of primary amines to nitriles is also reported.[28−31]

Aryl nitriles are useful organic compounds used in synthetic organic chemistry and natural product chemistry. Traditional methods for the preparation of aryl nitriles include Rosenmund–von Braun reactions, Sandmayer reactions, as well as dehydration of amides[5] and aldoximes.[6,32] Recently, it was reported that aryl nitriles could be obtained by various catalysts.[10,33,34] However, these methods involved toxic cyanating reagents, such as metal cyanides, harsh conditions, metal catalysts, and so forth. For the first time, we herein report a new approach for the conversion of primary aryl amines having no α-methylene to the corresponding aryl nitriles. Dimethyl carbonimidothioates 2(35) derived from various primary amines (1) could be converted to the diaziridine derivatives 3 by reacting with hydrazine (Scheme ). The diaziridine 3 on oxidation with LTA in refluxing xylene extrudes nitrogen, and intramolecular stabilization took place to give product 5.

Scheme 1

Conversion of Primary Aryl Amines to the Corresponding Aryl Nitriles via Carbonimidodithioates

Results and Discussion

The reaction of primary amines (1) having no α-methylene with carbon disulfide and methyl iodide in the presence of concentrated sodium hydroxide solution gave the corresponding dimethyl carbonimidothioates (2a–o).[36] The intermediate diaziridines, 3a–o, were obtained by the reaction with hydrazine hydrate in ethanol. The reactivity of the carbonimidothioates (2) is due to the facility to displace two molecules of HSMe as leaving groups,[36] when they react with hydrazine to give the corresponding diaziridines (3a–o) (Table ). On refluxing the diaziridines (3) with LTA in xylene yielded the corresponding nitriles 5a–o in 68–93% overall yields (Table ). The reaction may take place through the intermediate, diazirine 4 which has not been isolated (Scheme ).[37,38] The position of the substituent on the aromatic ring (ortho- or para-) did not show any significant effect on the product formation (Scheme ).

Table 1

Transformation of Diaziridines (3a–o) to Nitriles (5a–o)

Scheme 2

Transformation of Diaziridines (3a–o) to Aryl Nitriles (5a–o)

The probable mechanism for the oxidation of diaziridines 3 by LTA in refluxing xylene to afford the nitriles 5 is shown in Scheme . As it is difficult to intercept the carbenes, it is presumed that intramolecular rearrangement, particularly 1,2-carbon migration, takes place. It was reported that the low yields of bimolecular products obtained upon photolysis of diazirine were due to the inefficiency of carbine production from the precursor.[32,33] It was proposed that an excited state of diazirine suffers rearrangement, without intervention of carbine.

Scheme 3

Plausible Mechanism for the Conversion of Diaziridines to Nitriles

Conclusions

In conclusion, we herein report an oxidative conversion of a wide range of primary aryl amines (1), which have no α-methylene to the corresponding nitriles (5). This work provides a new approach to aryl nitriles.