Palladium on manganese ferrite: an efficient catalyst for one pot synthesis of primary amides from iodobenzene

Abstract

Amidation of aryl iodide in one pot is reported using Pd–MnFe₂O₄ as a catalyst. The catalyst was characterized by various techniques such as XRD, FEG-SEM, EDS, TEM, BET surface area and ICP AES. K₄[Fe(CN)₆]is used as a non toxic cyanation reagent for in situ generation of benzonitrile and hydrolyzed as soon as it formed. The catalyst was found to be efficient and can be used for several cycles without loss in activity. Good to excellent yields of primary amides were obtained.

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1. Introduction

Primary amides are the most important functionality in pharmaceuticals, natural products, agrochemicals and biologically active molecules.^1–3 Generally, primary amides are synthesized either by the reaction of carboxylic acid or its derivatives with ammonia or its equivalent.⁴ They are also synthesized by different methodologies such as catalytic rearrangement of aldoximes,⁶ reaction of aldehydes with ammonia,⁷ oxidation of benzylic alcohols in the presence of ammonia⁸ and catalytic oxidation of benzyl amines.⁹ Aminocarbonylation of aryl halide by using carbon monoxide and ammonia or ammonia equivalent is also reported as the efficient method for the synthesis of primary amides. However, this process involves handling of toxic gas and reduces its use at kilogram level.⁵ Aryl halides with ammonia in presence of metal carbonyls also have been used for the synthesis of primary amides, but it leads to release of toxic carbon monoxide gas and also the metal carbonyl complexes are volatile and unstable.¹⁰ Hydration of nitriles is an atom economical process and numbers of catalytic methods have been developed for nitrile synthesis.¹¹ Hence preparation of nitriles as an intermediate for amide synthesis is of great importance. Nitriles are prepared by reaction of aryl halides with various nitrile sources such as alkali cyanide, CuCN, TMSCN and K₄[Fe(CN)₆] salt in presence of transition metal catalyst. Among these K₄[Fe(CN)₆] is used as a less toxic and cheaper cyanide source for cyanation of aryl halides.¹²

Recently oxidation of benzyl amine to primary amide by using OMS-2 catalyst was reported.^9c However, the reaction requires very high pressure (6 bar) and temperature (160 °C) and also gives side products, where as we have reported general synthesis of primary amides at mild reaction conditions using magnetically retrievable catalyst.

Magnetically separable catalyst has attracted much attention in the area of heterogeneous catalyst as it is easily separated by external magnet and can be used several times without losing its activity.¹³ Super paramagnetic materials, spinel ferrites MFe₂O₄ (M = Ni, Co, Mn, Zn) are one of the important advance materials used in drug delivery and biomedical applications such as MRI.¹⁴ Besides this, they are also found to be good support for transition metal catalysts.¹⁵ In particular, palladium supported on super paramagnetic material is the most important heterogeneous catalyst as it offers high surface area and easy separation. In continuation of our work with metal nano particles supported on super paramagnetic material,^15b herein we report palladium nanoparticles (PdNPs) supported on MnFe₂O₄ and its application in one pot synthesis of primary amides (Fig. 1).

Fig. 1 General synthesis of primary amide.

Manganese ferrite (MnFe₂O₄) nano crystals possess higher magnetization as compared to magnetite, CoFe₂O₄ and NiFe₂O₄ nanoparticles.¹⁶ Here we have carried out the tandem synthesis of primary amide from iodobenzene via in situ generation of benzonitrile in presence of DMSO : H₂O solvent system using Pd nano particles supported on MnFe₂O₄. This is the first report of the application of the heterogeneous catalyst for the synthesis of primary amide and that too using nontoxic nitrile source K₄[Fe(CN)₆]. Very good yields of the desired products were obtained.

2. Experimental

2.1 Catalyst preparation

Catalyst was prepared by using ultrasound assisted coprecipitation method. FeCl₃·6H₂O (9.5 mmol, 50 mL) and MnCl₂·4H₂O (4.4 mmol, 50 mL) solutions were added in 250 mL round bottom flask followed by addition of 0.5 g KCl and PdCl₂ (60 mg). This mixture was placed in ultrasound bath for 5 min. Then pH of this mixture was adjusted at 12 by adding 3 N NaOH followed by heating at 60 °C for 30 min. The obtained catalyst was filtered and washed with distilled water several times and then by ethanol to remove water. The catalyst was dried under vacuum at 60 °C for 24 h, and subsequently at 200 °C for 4 h.

2.2 Characterization of material

The as synthesized catalyst was characterized by various techniques such as X-ray diffraction (XRD), Field emission gun scanning electron microscopy (FEG-SEM), Transmission electron microscopy (TEM), FTIR, ICP-AES analysis, BET surface area. The XRD analysis was performed on Shimadzu XRD 2400 instrument using Cu Kα radiation (λ = 1.5406 Å) with scanning rate 2 degree per minute. TEM analysis was performed over PHILIPS 2200 instrument. FEG-SEM analysis was performed on TESCAN MIRA Instrument. The energy dispersive X-ray spectral analysis (EDS) image was recorded with an Oxford instrument at 10 kV. Beam intensity was kept high to get good response by the detector. Inductively coupled plasma atomic absorption spectrometry (ICP AES) analysis was performed on ARCOS from M/s. Spectro, Germany. GC analysis is performed over PerkinElmer Clarus 480 instrument. GC-MS Spectra recorded over Shimadzu QP-2010 Instrument. ¹H and ¹³C NMR spectra's were recorded on Agilent 400 MHz and 100 MHz instrument respectively.

3. Results and discussion

XRD analysis showed peak at 2θ = 30.1, 35.14, 43.41, 54.601, 57.0671 and 63.6651 which represent the Bragg reflections from the (220), (311), (400), (422), (511) and (440) planes respectively. The crystalline data matches with the JCPDS Card no. (74-2403). Palladium peaks at 40, 46 θ values were not observed because of the low loading of the palladium (Fig. 2a). Displacing value from XRD and TEM SEAD pattern is same and found to be 2 Å (Fig. 3c and d).

Fig. 2 (a) XRD and (b) EDS analysis of Pd–MnFe₂O₄.

Fig. 3 FEG-SEM image (a) fresh and (b) reused catalyst after fifth cycle. (c) TEM image of catalyst and (d) SEAD pattern.

The elemental analysis of Pd–MnFe₂O₄ was confirmed by EDS analysis as shown in Fig. 2b. The distribution of elements in Pd–MnFe₂O₄ was Mn = 11.45%, Fe = 28.15%, O = 59.31% and Pd = 1.09%.

FEG-SEM analysis shows highly crystalline morphology of the catalyst (Fig. 3a and b).

The TEM image of Pd–MnFe₂O₄ NPs (Fig. 3c) clearly indicates that NPs are uniform in size with average particle size less than 45 nm. This is in accordance with the average crystallite size obtained by using the Debye–Scherrer equation. The image also exhibits that the Pd NPs on MnFe₂O₄ are well dispersed. Pd NPs size ranges from 2–10 nm.

From the N₂ adsorption–desorption isotherm of Pd–MnFe₂O₄ NPs, the BET surface area of the particles was found to be 24.9346 m² g⁻¹ and the adsorption average pore width was 315 Å. Single point surface area at P/P_o = 0.254238207 : 24.5190 m² g⁻¹ (Fig. 2 ESI†).

Reaction of iodobenzene with K₄[Fe(CN)₆] was treated as a model reaction and various reaction parameters were optimized for this reaction. Initially (1 mmol) of iodobenzene was treated with 0.25 mmol of K₄[Fe(CN)₆] in the presence of Pd–MnFe₂O₄ catalyst (30 mg, 1 mol% Pd), K₂CO₃ as a base in DMF : H₂O (1 : 1) solvent system, at 100 °C, which offered 58% yield of benzamide (Table 1, entry 1). Series of experiments were performed to optimize the various reaction parameters such as catalyst loading, solvent, base and temperature of the reaction (Scheme 1).

Table 1 Optimization of reaction parameters^a

Entry	Pd–MnFe2O4 (mol%)	Base	Solvent : H2O	Temperature (°C)	Yield^b (%)
a Reaction conditions: aryl halide (1 mmol), K4[Fe(CN)]6 (0.25 mmol), time 12 h, base (1.2 mmol).b Isolated yield.c Time 18 h.d 24 h.e Benzonitrile 92%.
1	0.5	K2CO3	DMF : H2O (1 : 1)	100	58
2	0.5	K2CO3	NMP : H2O (1 : 1)	100	64
3	0.5	K2CO3	DMSO : H2O (1 : 1)	100	70
4	1	K2CO3	DMSO : H2O (1 : 1)	100	78
5	1	K2CO3	DMSO : H2O (2 : 1)	100	84
6	1	K2CO3	DMSO : H2O (2 : 1)	110	88
7	2	K2CO3	DMSO : H2O (2 : 1)	110	88
8	3	K2CO3	DMSO : H2O (2 : 1)	110	88
9	1	Cs2CO3	DMSO : H2O (2 : 1)	110	74
10	1	TEA	DMSO : H2O (2 : 1)	110	Trace
11	1	DBU	DMSO : H2O (2 : 1)	110	Trace
12	1	KOH	DMSO : H2O (2 : 1)	110	20
13	1	K2CO3	DMSO : H2O (2 : 1)	90	19
14	1	K2CO3	DMSO : H2O (2 : 1)	120	91
15	1	K2CO3	DMSO : H2O (2 : 1)	140	90
16	1	K2CO3	H2O	110	—
17	1	K2CO3	DMSO	110	—^e
18	1	K2CO3	DMSO : H2O (2 : 1)	110	90^c
19	1	K2CO3	DMSO : H2O (2 : 1)	110	90^d

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Scheme 1 One pot synthesis of amide from iodobenzene.

Loading of the catalyst was also the important parameter and it was found that 1 mmol of the catalyst was enough to achieve the maximum yield of the desired product (Table 1, entry 4). Solvent study was the important part for this transformation. Various solvent systems such as DMF : H₂O, DMSO : H₂O and NMP : H₂O were used out of which DMSO : H₂O (2 : 1) was found to be the most suitable solvent system for this transformation (Table 1, entry 5). When reaction was carried out in DMSO solvent only, benzonitrile was formed (Table 1, entry 17). Iodobenzene was in situ converted to benzonitrile by the cyanating reagent K₄[Fe(CN)₆] which immediately gets hydrated to benzamide in the presence of water.

The reaction was also carried out with various inorganic and organic bases such as TEA, DBU, K₂CO₃, KOH and Cs₂CO₃, out of which K₂CO₃ was found to be the most efficient base giving maximum yield of the benzamide (Table 1, entry 8). The reaction was also carried out at various temperatures under optimized reaction conditions. The product yield increased dramatically from 19% to 90% when temperature increased from 90 °C to 110 °C whereas beyond 110 °C no significant increase in the product yield with increase in temperature was observed (Table 1, entries 13–15).

We also studied the effect of concentration of K₄[Fe(CN)₆] salt on the product yield by increasing the amount from 0.1 mmol to 0.25 mmol. Conversion of aryl halide to benzonitrile was 100% at 0.25 mmol concentration of K₄[Fe(CN)₆]. The reaction was also carried out at various time intervals and 100% conversion was obtained in 18 h. For optimized reaction TON and TOF‡ for amidation of iodobenzene was found to be 90 and 5 h⁻¹.

The applicability of the protocol was examined for various substituted aryl iodides (Table 2). It was found that electron rich substrate gave very good yield of the desired product.

Table 2 One pot synthesis of primary amides from aryl iodides^a

Entry	Iodobenzene	Amide	Yield
a Reaction conditions: aryl halide (1 mmol), K4[Fe(CN)6] (0.25 mmol), 12 h, base (1.2 mmol), Pd–MnFe2O4 (30 mg, 1 mol% Pd).b Isolated yield.
1			90
2			20
3			—
4			88
5			90
6			80
7			88
8			90
9			88
10			90
11			78
12			84
13			84
14			88
15			85
16			81

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In case of p-NO₂ iodobenzene electron withdrawing effect was more prominent giving moderate yield of the desired products. However, in m-nitro iodobenzene the yield was increased due to minimum electron withdrawing effect. Results are summarized in Table 2 (entries 6 and 11).

Donating substituents at ortho positions were well tolerated giving good yield of the corresponding primary amides. We further studied amidation of bromobenzene as well as chlorobenzene and observed that bromobenzene gave only 20% yield of the desired product whereas chlorobenzene was unreactive with optimized reaction conditions (Table 2, entries 2 and 3). Heteroaryl iodide also gave good yield of corresponding amide (Table 2, entry 16).

3.1 Heterogeneous test for the catalyst

We also examined the heterogeneous nature of the catalyst by hot filtration test. The catalyst was separated by using external magnet from reaction mass after half of the reaction time and the filtrate was stirred for required time under same reaction conditions. The reaction did not proceed further, which indicated that there is no leaching of palladium during the reaction. We also carried out the ICP AES analysis to test the recyclability of the catalyst for first and fifth cycles which showed that the palladium leaching was below detectable level (0.01 ppm) (Fig. 4 and 6).

Fig. 4 Recycle study of the catalyst.

Fig. 5 Plausible mechanism of the reaction.

Plausible mechanism suggests that iodobenzene is oxidatively added to the catalyst and then in presence of K₄[Fe(CN)₆] salt gives benzonitrile which subsequently get hydrolyzed in presence of water and catalyst to give primary amide (Fig. 5).

Fig. 6 Magnetic separation of the catalyst (a) before and (b) after applying external magnet.

4. Conclusions

In summary, we have developed the simple and practically applicable protocol for the synthesis of primary amides from aryl iodides. Pd–MnFe₂O₄ is the first heterogeneous catalyst for such transformation. Catalyst was found to be efficient for the transformation of iodobenzenes to respective amides. K₄[Fe(CN)₆] was used as the non toxic cyanating reagent and in situ generated benzonitrile was hydrated as soon as it forms. The catalyst can be retrieved using external magnet and reused up to five consecutive cycles without much loss in its activity.

Acknowledgements

The authors are very thankful to the UGC-SAP, New Delhi, India for awarding the fellowship.

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Footnotes

† Electronic supplementary information (ESI) available: Experimental procedure, characterization of the catalyst, mass and 1H NMR spectrum of representative compounds are given. See DOI: 10.1039/c4ra12827c

‡ TOF = [mole of product/(mole catalyst × h)].

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