An Integrated Carbon Nitride‐Nickel Photocatalyst for the Amination of Aryl Halides Using Sodium Azide

Abstract The synthesis of primary anilines via sustainable methods remains a challenge in organic synthesis. We report a photocatalytic protocol for the selective synthesis of primary anilines via cross‐coupling of a wide range of aryl/heteroaryl halides with sodium azide using a photocatalyst powder consisting of nickel(II) deposited on mesoporous carbon nitride (Ni‐mpg‐CN x ). This heterogeneous photocatalyst contains a high surface area with a visible light‐absorbing and adaptive “built‐in” solid‐state ligand for the integrated catalytic Ni site. The method displays a high functional group tolerance, requires mild reaction conditions, and benefits from easy recovery and reuse of the photocatalyst powder. Thereby, it overcomes the need of complex ligand scaffolds required in homogeneous catalysis, precious metals and elevated temperatures/pressures in existing protocols of primary anilines synthesis. The reported heterogeneous Ni‐mpg‐CN x holds potential for applications in the academic and industrial synthesis of anilines and exploration of other photocatalytic transformations.


General information
Reagents used in this study were of the highest available purity acquired from commercial suppliers and used directly without any further purification, unless mentioned otherwise. Mesoporous, pristine and cyanamide functionalized carbon nitride were synthesized according to previously reported procedures. 1,2 Products were purified by flash column chromatography on silica gel 60 (0.040-0.063 mm mesh) from Material Harvest. Thin layer chromatography (TLC) was carried out on aluminum Merck Kieselgel 60 F254 sheets, visualized by ultraviolet irradiation (254 and 365). 1 H and 13 C NMR spectroscopy were recorded on a Bruker DPX 400 spectrometer at room temperature. Chemical shifts (δ) of 1 H and 13 C NMR spectra are given in ppm and the peaks were internally referenced against the residual solvent peak (CDCl3 referenced at δ 7.26 ppm for 1 H and 77. 16 ppm for 13 C). NMR data were reported in the following form: Chemical shift, multiplicity, coupling constant and integration. Inductively coupled plasma-optical emission spectroscopy (ICP-OES) was carried-out in the Yusuf Hamied Department of Chemistry, University of Cambridge with a Perkin-Elmer ICP-OES chemical analyzer. Attenuated total reflection Fourier transform infrared (ATR-IR) spectra were recorded on a Nicolet iS50 spectrometer and reported in terms of absorption frequency (cm -1 ). UV-vis diffuse reflection spectroscopy (DRS) of powder materials was carried out on an Agilent Cary 60 machine. Mass spectra were recorded on a Waters LCT premier Time of Flight mass spectrometer or Micromass Quadrupole-Time of Flight mass spectrometer. Reported mass values are within the error limits of 5 ppm.

ICP-OES sample preparation
The nickel loading in the materials was determined by ICP-OES after digestion of the material (<1 mg) in concentrated HNO3 (70%) (~1 mL) overnight and dilution to 10 mL with Milli-Q ® water. The ICP-OES data are shown in Table S1.
Preparation of mesoporous carbon nitride (mpg-CNx) 1 Cyanamide (3 g) was heated at 50 ºC until it completely melted and then a 40 wt.% dispersion of SiO2 in water (7.5 g, Ludox HS) was added to form a homogeneous solution. The resultant transparent mixture was heated at 100 o C to form a white solid. The white solid was ground and transferred to an alumina crucible and heated at a ramping rate of 2.3 °C min -1 to reach a temperature of 550 o C, and then kept at this temperature for a further 4 h under normal atmosphere (air). The resulting brown-yellow powder was treated with 4 M NH4HF2 for 24-48 h to remove the silica template. The powders were then washed three times with hot distilled water, ethanol, and acetone over suction filtration. 3 In a 20 mL alumina crucible, 5 g of melamine was taken and heated at 550 o C for 3 h at the ramping rate of 10 o C per min under atmospheric condition. Pristine carbon nitride was obtained as yellow powder (3 g), which was grinded for 5-10 min using mortar and pestle till fine powder. 4 A mixture of pristine CNx and KSCN (weight ratio 1:2) was prepared and heating first to 400 o C for 1 hour followed by 500 o C for 30 min with the ramping rate 30 o C min -1 under Ar atmosphere. After cooling naturally, the powder was washed with H2O and dried under vacuum at 60 o C. 5 In a 20 mL microwave vial charged with a magnetic bead, mpg-CNx (0.3 g) was suspended in dry acetonitrile (12 mL), purged with N2 and ultrasonicated for 10 min. Anhydrous NiCl2 (50 mg) and anhydrous triethylamine (0.15 mL) were added to the suspension and the mixture was purged again for 5 min under N2. The suspension was stirred at room temperature for 30 min, followed by heating under microwave at 80 o C for 2 h. After cooling to room temperature, the resulting yellow solid was collected by filtration sequentially washed with acetonitrile, hot water, boiling ethanol, boiling methanol, boiling acetone, and dried under vacuum. The material was characterized with powder X-ray, attenuated transmission reflectance Infra-ray (ATR-IR) and UV-Vis diffuse reflectance (UV DRS), which matches with the reported literature ( Figure S2-S4). 5

General procedure for photocatalytic C-N coupling reactions
All photocatalytic experiments were performed using blue LED photoreactors (λ = 447 ± 20 nm, 1.03 W @ 700mA per LED) as a light source. 6 In a 10 mL borosilicate photoreactor vial charged with four glass beads (6 mm), Ni-mpg-CNx (10 mg), aryl halide (0.4 mmol) and sodium azide (2 mmol, 5 equiv.) were added. The vial was crimped by a septum-aluminum cap and purged with N2 atmosphere via "vacuum and N2 refill" cycles (x3). Then, 2 mL of a degassed methanol:water mixture (5:3) was added as a solvent and purged with N2 atmosphere, followed by addition of triethylamine (0.8 mmol, 2 equiv.) using a syringe. The reaction mixture was then shaken rapidly using an orbital stirrer and irradiated using blue LEDs at 60 o C ( Figure  S7). The reaction was monitored by TLC. Upon completion of the irradiation, the reaction mixture was purified by flash column chromatography. In case of the optimization study, 1,3,5trimethoxybenzene (50 μmol) was added to the reaction mixture as internal standard and submitted for NMR in deuterated acetonitrile. A general representation of 1 H NMR spectra used during optimization studies is presented in Figure S6.

General procedure for the recovery of the material after catalytic studies
After completion of the reaction, the mixture was centrifuged at 1000 rpm for 10 min. The recovered material was washed again with water and acetone, centrifuged and the collected solid dried overnight. More than 90% of the material can be recovered. 7 4-Aminobenzonitrile (5 mmol, 590 mg) was add to a 50 mL round bottom flask charged with a magnetic bead and purged with N2. A solution of 1 M HCl (15 mL) was added, and the contents cooled to 0 o C using an ice bath. A solution of NaNO2 (1.2 equiv.) in water (2mL) was added to the reaction mixture drop wise at <5 o C and stirred for 20 min. To the mixture, NaN3 (1.5 equiv.) in water (2 mL) solution was added at 0 o C and the obtained suspension was stirred for 24 h. The solution was extracted with diethyl ether using separation and further washed with brine solution. The organic layer was dried over MgSO4, filtered, and concentrated under reduced pressure. The residue was further purified by column chromatography (10 % EtOAc: Hexane) to give a pale-yellow powder with 86% yield (624 mg).

Computational studies
DFT calculations have been performed with the Gaussian09 software package. 8 First, geometry optimizations and frequency calculations of the ground state structure of a simplified model for the Ni-mpg-CNx system have been performed at the B3LYP/6-31G* level of theory ( Figure S8). 5,[9][10][11] Solvent effects (MeOH) are considered with the polarizable continuum model PCM-SMD of Truhlar and coworkers. [12][13][14][15] Additionally, the energy of the geometry optimized molecules was refined by single point calculation with the cc-pVTZ basis set for all atoms. 16,17 Standard reduction potentials (E°) have been evaluated through the Nernst equation in standard state conditions using the Standard Hydrogen Electrode ( ) as reference following the equation 1: is the free energy change associated with reduction at standard conditions, n is the number of electrons involved in the redox reaction, F is the Faraday constant and is the free energy change associated with the reduction of a proton (-4.28 eV). 18 All energies given in this work are referred to Gibbs energies G in kcal mol -1 , unless otherwise noted. The nature of the stationary points was established by frequency calculations in the solvent-phase, in which minima have no imaginary frequencies.

Redox potentials
The possibility to have a first reduction of the Ni(II) center in Ni-mpg-CNx to Ni(I) after photoinduced electron transfer (PET) from the mpg-CNx matrix to the Ni site and then a subsequent reduction to Ni(0) by intramolecular PET was evaluated: Considering that the potential of the CNx conduction band is -0.5 V vs. SHE, the reduction of Ni(II) to Ni(I) within the mpg-CNx matrix is possible (0.33 V vs SHE), but not a second reduction of the Ni(I) to Ni(0) (-1.51 V vs SHE). The calculated energy profile and the proposed catalytic cycle is represented in Figure S9-S10.

Products characterization
The products are reported from the aryl bromide substrates, unless otherwise mentioned.

4-Aminobenzonitrile
The reaction was completed in 24 h and the desired product (yellow powder, 84% yield) was obtained by flash chromatography (20% ethyl acetate/hexane). 1  The reaction performed with 4-iodo benzonitrile was completed in 20 h. The reaction yielded 65% of the desired aniline product and the dehalogenated side product was observed with 25% NMR yield.
The reaction performed with 4-chloro benzonitrile was stopped after 60 h. The reaction proceeded to 48% conversion with 21% of the desired product. Side products resulted from hydrolysis of the nitrile group.

1-(4-Aminophenyl)ethan-1-one
The reaction was completed in 40 h and the desired product (brown powder, 83% yield) was obtained by flash chromatography (20% ethyl acetate/hexane). 1  The reaction performed with 4-iodo acetophenone was completed in 40 h. The reaction yielded 74% of the desired aniline product and the dehalogenated side product was observed with 20% NMR yield.
The reaction performed with 4-chloro acetophenone was stopped after 60 h. The reaction proceeded to 25% conversion with 23% of desired product.

Methyl 4-aminobenzoate
The reaction was completed in 40 h and the desired product (brown powder, 84% yield) was obtained by flash chromatography (20% ethyl acetate/hexane). 1  The reaction performed with methyl 4-Iodobenzoate was completed in 40 h. The reaction yielded 76% of the desired aniline product and the dehalogenated side product was observed with 16% NMR yield.
The reaction performed with methyl 4-chlorobenzoate was stopped after 60 h. The reaction proceeded 24% conversion with 22% of desired product.

4-aminobenzamide
The reaction was completed in 40 h and the desired product (brown powder, 83% yield) was obtained by flash chromatography (ethyl acetate). 1

4-Aminobenzophenone
The reaction was completed in 40 h and the desired product (brown powder, 75% yield) was obtained by flash chromatography (20% ethyl acetate/hexane). 1

2-Aminobenzonitrile
The reaction was completed in 40 h and the desired product (brown powder, 76% yield) was obtained by flash chromatography (10% ethyl acetate/hexane). 1

4-Bromoaniline
The reaction was stopped after 60 h and, 68% conversion was observed in proton NMR spectroscopy. The desired product (white powder, 56% yield) was obtained by flash chromatography (20% ethyl acetate/hexane). 1

4-Aminobiphenyl
The reaction was completed in 60 h and the desired product (white powder, 72% yield) was obtained by flash chromatography (20% ethyl acetate/hexane). 1

Pyridin-3-amine
The reaction was completed in 40 hours and the desired product (brown powder, 87% yield) was obtained by flash chromatography (2% methanol/ethyl acetate). 1

Pyrimidin-5-amine
The reaction was completed in 24 hours and the desired product (brown powder, 67% yield) was obtained by flash chromatography (2% methanol/ethyl acetate). 1

6-Aminonicotinonitrile
The reaction was completed in 50 hours and the desired product (white powder, 74% yield) was obtained by flash chromatography (80% ethyl acetate/hexane). 1

Ethyl 4-aminobenzoate
The reaction employed ethanol as a solvent instead of methanol and was completed in 50 hours. The desired product (white powder, 83% yield) was obtained by flash chromatography (20% ethyl acetate/hexane). 1

4-Aminobenzenesulfonamide
The reaction was completed in 50 hours and the desired product (white powder, 85% yield) was obtained by flash chromatography (ethyl acetate). 1 Tables   Table S1. ICP-OES data for different Ni deposited carbon nitrides.          Figure S1. TEM image of Ni-mpg-CNx. Figure S2. pXRD spectra of Ni-mpg-CNx. The peaks present at 27 and 12 confirm the stacking and in-plane periodicity, respectively. 5 Figure S3. ATR-IR spectra of Ni-mpg-CNx. The peak at 804 cm -1 is consistent with the characteristic vibration of the heptazine core.