Green and efficient synthesis of dibenzyl cyanamides and ureas with cyanamide as a block

Abstract

A method for the two-step synthesis of dibenzyl cyanamide and dibenzyl urea via cyanamide is presented. This approach is both efficient and environmentally friendly. Various N,N-dibenzyl ureas could be obtained by reactions of N,N-dibenzyl cyanamides and N,N-dibenzyl cyanamides as intermediates formed from cyanamide. In the absence of metal, ligand and hydrogen peroxide as the oxidant, products with moderate yields have been obtained under mild conditions. Key features include the use of widely available and easily handled cyanamide sources as starting materials.

Scheme 1. Synthesis of N,N-functionalized cyanamides or ureas.

Scheme 2. The substrate scope of the N,N-functionalized cyanamide 3. Conditions of reaction: 1a (0.44 mmol), 2a (0.20 mmol), K₂CO₃ (0.60 mmol) in MeCN (5 mL) stirred for 5 h at 80 °C at air, isolated yields.

Scheme 3. Substrate scope of the N,N-functionalized urea 4. Reaction conditions: 3a (0.20 mmol), H₂O₂ (0.24 mmol, 30% a.q.), K₂CO₃ (0.20 mmol) in DMSO (3 mL) stirred for 4 h at r.t. under air, isolated yields.

Scheme 4. Gram-scale synthesis of 4a. Conditions of reaction: 1a (22.0 mmol), 2a (10.0 mmol), K₂CO₃ (30.0 mmol) in MeCN (25 mL) stirred for 5 h at 80 °C under air atmosphere, isolated yields; 3a (8.1 mmol), hydrogen peroxide (9.7 mmol), K₂CO₃ (8.1 mmol) in DMSO (15 mL) stirred for 4 h at r.t. under air, isolated yields.

Scheme 5. Synthesis of derivatives 5a. Reaction conditions: 3d (0.2 mmol), CuI (0.02 mmol), t-BuOK (0.6 mmol) in DMSO (2 mL) stirred for 8 h at 130 °C under air, isolated yields.

Scheme 6. Proposed mechanism.