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Article

A New Pd-Based Catalytic System for the Reductive Carbonylation of Nitrobenzene to Form N-(4-hydroxyphenyl)acetamide Selectively in One Pot

by
Andrea Vavasori
*,
Marco Capponi
and
Lucio Ronchin
Department of Molecular Science and Nanosystems, Ca’ Foscari University Venice, Via Torino 155, 30172 Venezia, Italy
*
Author to whom correspondence should be addressed.
Reactions 2023, 4(4), 725-736; https://doi.org/10.3390/reactions4040042
Submission received: 25 August 2023 / Revised: 11 September 2023 / Accepted: 10 November 2023 / Published: 17 November 2023
(This article belongs to the Special Issue Traditional and Innovative Catalysts for Reactions of Industrial Interest)
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Abstract

:
N-(4-hydroxyphenyl)acetamide (commonly named paracetamol or acetaminophen) is a target molecules for many industries that produce chemicals for pharmaceutical applications. The industrial processes, however, use multistep procedures with low overall yield and/or severe drawbacks and problems in terms of sustainability. In the present paper, a one-pot synthesis is proposed based on the reductive carbonylation of nitrobenzene catalyzed by Pd(II)-complexes. Usually, such a reaction leads to a mixture of different products, including aniline, 4-aminophenol and 1,3-diphenylurea. However, the selectivity towards the possible products strongly depends by the ligands on the Pd(II)-catalyst, but also by the nature of the solvent. According to this, we have found that when the reaction was carried out in dilute acetic acid as a solvent, the [PdCl2(dppb)] catalyst precursor leads in one pot to N-(4-hydroxyphenyl)acetamide. Under optimized reaction conditions, it was possible to produce N-(4-hydroxyphenyl)acetamide with a 85 mol % of selectivity in ca. 5 h.

1. Introduction

The synthesis of N-(4-hydroxyphenyl)acetamide (commonly named paracetamol or acetaminophen) has long been attracting the interest of many industries which produce chemicals for pharmaceutical applications, since it is the main ingredient in numerous cold and flu medications [1,2,3,4,5]. Over the last century, among the several routes proposed for acetaminophen production, those that have emerged industrially have used raw materials such as phenol [6,7,8], 4-nitrophenol [9], or nitrobenzene [10,11,12,13,14,15,16]. The corresponding industrial processes, however, have drawbacks and problems in terms of sustainability, mainly due to the use of multistep production procedures with low overall yield and/or severe effluent problems [17,18,19,20,21,22,23]. For instance, phenol is first nitrated to 4-nitrophenol, which is reduced to 4-amminophenol, and finally N-acetylated to N-(4-hydroxyphenyl)acetamide [3,4,5,6]. Alternatively, phenol can be first acetylated with acetic anhydride to 4-hydroxyacetophenone (e.g., in the Hoechst-Celanese process), which is then converted into the corresponding oxime through reaction with hydroxylamine [7]: in the last step, the acid-catalyzed (H2SO4) Beckmann’s transposition forms acetaminophen [11,24,25,26,27,28,29]. This route is very attractive, but suffers from moderate selectivity (aniline is obtained as a by-product) and problems related to the corrosion and the pollution due to the large quantities of sulfate salts generated. To improve the sustainability of such a step, several authors have proposed alternative catalysts for the Beckmann’s transposition, to use instead of sulfuric acid [30,31,32,33,34,35,36,37,38,39]. On the other hand, new promising routes have been proposed, for instance starting again from phenol but involving at first its direct oxidation to hydroquinone, followed by reaction with acetamide to acetaminophen [40,41]. Similarly, the syntheses of acetaminophen based on nitrobenzene or 4-nitrophenol require, in general, more than two steps, including the selective NO2-reduction and the acetylation. For instance, the catalytic hydrogenation of 4-nitrophenol leads directly to 4-aminophenol [32,36,42,43,44,45,46,47,48], which is then acetylated to N-(4-hydroxyphenyl)acetamide. Alternatively, N-phenyl(hydroxylamine) can be produced from nitrobenzene in a first step, which is then converted in one pot into 4-aminophenol through the catalyzed Bamberger’s rearrangement [9,10,11,12,13,32,45,46,47,48,49,50,51,52], followed by the acetylation step. Nowadays, although many solutions have been adopted (or only proposed) to further improve the sustainability of such industrial processes, the realization of a more efficient and eco-friendly process for the production of acetaminophen still represents an interesting target for numerous academic and industrial researchers [53,54,55,56,57,58].
In the present paper, the authors reported the synthesis of acetaminophen carried out in one pot, starting from nitrobenzene through the Pd-catalyzed reductive carbonylation of the nitro-group in water–acetic acid as a solvent. As pointed out in previous papers, the choice of the catalyst plays a key role in determining the selectivity of such reaction, but no less important is the influence of the solvent. For instance, the Pd-catalyzed reductive carbonylation of nitrobenzene can readily lead to aniline in high yield when methanol was used as a solvent, but the addition of a co-solvent can strongly influence the selectivity [57,58,59,60,61,62,63,64,65,66,67,68,69,70,71]. According to this, we reported the selective synthesis of 1,3-diphenylurea in one pot by using an appropriate methanol–acetic acid mixture as a solvent [71]. On the other hand, in the same reaction when H2O–acetic acid was used as a solvent, the selectivity moved again toward the aniline as the main products, even if traces of acetaminophen was also found in the by-products [72]. This suggested to us the chance to obtain acetaminophen in one pot and in high yield. Therefore, the [PdCl2(dppb)] (dppb = 1,4 bis(diphenylphosphine)butane) complex has been selected to carry out the reaction (reaction 1) first, and the influence of some reaction parameters have been studied, with the aim of increasing the selectivity towards acetaminophen.
Reactions 04 00042 i001

2. Materials and Methods

2.1. Reagents

The Pd(II)-diphosphine complexes were prepared as reported in the literature [71,73] and characterized by FTIR and NMR analysis. Carbon monoxide was supplied by SIAD Company, Bergamo, Italy (‘research grade’, purity > 99.9%); PdCl2, nitrobenzene (NB), acetic acid-glacial (AcOH), 1,2-bis(diphenylphosphino)ethane (dppe), 1,3-bis(diphenylphosphino)propane (dppp), 1,4-bis(diphenylphosphino)butane (dppb), 1,1′-bis(diphenylphosphino)ferrocene (dppf), 4-aminophenol, N-(4-hydroxyphenyl)acetamide, aniline, acetanilide, 2-aminophenol, (9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphane) (Xantphos), N-(2-hydroxyphenyl)acetamide, 1,3-diphenylurea, N,N′-azobenzene, and N,N′-oxy-azobenzene were Aldrich/Merck products.

2.2. Equipment and Characterization

The catalyst precursors have been weighted on a Sartorious Micro balance (precision 0.001 mg). High-performance liquid chromatography (HPLC) analyses were carried out by a Perkin Elmer 250 equipped with a diode array LC-235 detector and a Lichrosphere 100 (RP-18, 5 μm) column employing water acetonitrile mixtures as eluent; the concentrations of the reagent and products were calculated by calibration with standard solution. GC/MS analyses were performed on a MS Agilent apparatus 5975C Model, interfaced with an Agilent chromatograph 7890 A Model equipped with a HP1 column (30 m × 0.25 mm × 0.25 μm, oven: 45 °C (3 min) to 250 °C at 15 °C/min). Fourier transform infrared (FTIR) spectra were recorded on a Nicolet Magna 750 instrument in KBr powder. All the NMR spectra were recorded on a Bruker Avance 300 spectrometer.

2.3. Catalytic Reactions

The catalysis has been carried out in a batch reactor of ca. 60 mL provided with a magnetic stirrer. In a typical experiment, 2.48 × 10−3 mmol of Pd(II) complex (for instance 1.50 mg of [PdCl2(dppb)]), together with 0.5 mL (0.600 g, 4.87 mmol) of nitrobenzene, were added to 11.5 mL of solvent (H2O-AcOH). In order to avoid catalyst deactivation due to the presence of air, the reactor was carefully flushed with CO at room temperature with stirring and then pressurized with 0.5 MPa of CO and heated up to 373 K in ca. 10 min without stirring. The pressure was then adjusted to the desired value (typically 5.0 MPa of total pressure) and, while stirring, maintained constant throughout the experiment (3 h) by continuously supplying the carbon monoxide from a reservoir. At the end of each experiment, the reactor was quickly cooled and carefully depressurized.
The reaction products were detected and quantified by the HPLC and GC-MS analysis. All the experiments were repeated at least twice, and the error analysis confirmed the reproducibility of the data within an error of ±1%.

3. Results and Discussion

3.1. Preliminary Experiments

Table 1 shows the results of the preliminary experiments carried out by using some Pd(II) complexes as catalyst precursors in H2O-acetic acid as a solvent. The reaction conditions adopted in such tests were typically used in a previous paper to produce 1,3-diphenylurea [71]. Among the complexes tested, the [PdCl2(dppb)] led to the best conversion (60 mol %, TON = 1178 mol/mol, entry 3), forming, under reaction conditions adopted, aniline (33%), and acetanilide (25%), together with 4-aminophenol (19%) and acetaminophen (8%), whereas only a trace amount of 1,3-diphenylurea was detected.
The experiments have been limited to such complexes because they are stable, easily handled at room temperature Pd(II) and effective in several carbonylation reactions, including the reductive carbonylation of nitrobenzene to 1,3-diphenylurea carried out in methanol as a solvent [71,72]. In addition, they are interesting from an industrial point of view, being readily synthesized from commercially available reagents and are very soluble in several solvents (e.g., alcoholic solvents or in H2O-acetic acid mixture, as in the present case). The results in Table 1 suggest that both catalytic activity and selectivity are strongly influenced by the electronic and steric characteristics of the chelating di-phosphine ligands, according to the studies reported in literature [71,73].
Furthermore, the Table 1 shows also that the nature of ionic ligand have poor influence on the conversion and selectivity under the reaction conditions. This could be ascribed to the nature of the solvent mixture used, in which the amount of acetic acid determinates the solubility of the complexes, whereas H2O has a key role to form the desired products (see mechanism), but also in determining the dielectric constant of the reaction medium. The latter could favor the solvation and the displacement of ionic ligands from the coordination site of the metal center. In such a way, it is plausible to suppose that such sites become more available for the coordination of the reagents, regardless of the coordinating ability of the ionic ligands.
On the basis of such preliminary results, the [PdCl2(dppb)] complex has been used as catalyst precursor in all the following experiments.

3.2. One-Pot Synthesis of Acetaminophen in H2O-Acetic Acid as a Solvent

Figure 1 and Table 2 show that the solvent composition strongly influences the conversion and the selectivity to acetaminophen. In fact, the conversion of nitrobenzene increases by increasing the amount of H2O in the reaction medium, reaching ca. 100 mol % at H2O 60 mol % (H2O/acetic acid 60/40 mol/mol). At H2O higher than 65 mol %, the conversion sharply decreases (it was ca. 22 mol % at H2O = 80 mol %), probably due to the separation of two liquid phases (nitrobenzene and water) observed at the end of such an experiment.
As schematized in Scheme 1, in order to simplify the discussion, we have indicated the molar sum of 4-aminophenol and its acetylated derivative with A, the molar sum of aniline and its acetylated derivative with B, and the molar sum of 2-aminophenol and its acetylated derivative with C. D indicates the molar sum of some compounds that, under the experimental conditions adopted, were each formed in concentration < 5 mol % (by-products), such as 1,3-diphenylurea, nitrosobenzene, N,N′-azobenzene, etc.
Regarding the selectivity to A, it increases with the amount of H2O in the solvent, reaching 40 mol % when H2O was ca. 60 mol % (see Table 2, entry 5).
The acid concentration, however, also influences the yield of acetylation. For instance, the percent of acetaminophen in A was 1 mol % when AcOH in H2O was 40 mol % (Table 3, entry 1; for conversion 99 mol %, see Table 2, entry 5), whereas it was 72 mol % when AcOH in H2O was 93 mol % (Table 3, entry 5; for conversion 39 mol %, see Table 2, entry 1). The same trend was observed for aniline and acetanilide in B composition (see Table 3).
In light of such results, and with the aim to increase the conversion and the selectivity to acetaminophen at the same time, we have carried out the following experiments by using a solvent dilution such as H2O/acetic acid = 50/50 (mol/mol).

3.3. Influence of Pressure and Temperature on Conversion and Selectivity

The conversion of nitrobenzene linearly increases with the pressure of carbon monoxide in the range 0–6.0 MPa (Table 4), whereas under 5.0 MPa of CO, the conversion reaches its maximum (100%) between 393 K and 403 K (Table 5).
The decrease of conversion observed at temperatures higher than 410 K could be ascribed to the progressive thermal decomposition of the Pd(II) complex, which leads to a loss of catalytic activity [71]. Focusing on the reaction at 403 K, it can be observed that nitrobenzene was fully converted with 85 mol % of selectivity towards A, which contains ca. 95 molar % of acetaminophen (see Figure 2). However, under the last conditions but with an increasing reaction time (e.g., 5 h), it was possible to obtain a selectivity of 85 mol % towards A, containing 100% acetaminophen.

3.4. On the Reaction Mechanism

The catalytic reductive carbonylation of nitrobenzene (or nitro-arenes), to form aniline, 1,3-diphenylurea, N-phenylisocyanates, or carbamate (in alcoholic solvents), has been extensively studied by several authors, who generally have proposed a reaction mechanism starting from a Pd (0) species, usually formed in situ from a Pd(II) precursor [69,70,71,72]. Such a species can activate the reaction of nitrobenzene with CO to form a complex which eliminates CO2 to lead to the Pd(II)-nitroso species 1 (see Scheme 2, reaction a). As schematized, following the reaction pathway b′–d′, the species 4′ can form which, in turn, can lead to aniline (reaction e′, together with azo-benzene), 1,3-diphenylurea (reaction e″) and/or N-phenylisocyanates (reaction e‴, together with carbamate in alcoholic solvents) [71].
However, when the reaction has been carried out in H2O-acetic acid as a solvent, 4-aminophenol together with aniline and the corresponding acetylated products (not included in the scheme) are mainly formed whereas azo-benzene and 1,3-diphenylurea are detected only in trace amounts (<5 mol %).
Since aniline, azo-benzene and 1,3-diphenylurea were formed even under the experimental conditions of the present work, we can assume the mechanism proposed in the literature is still effective. However, to also include the formation of 4-aminophenol, it is necessary to suppose the presence of parallel reaction pathways. For instance, we can suggest two hypotheses: (i) 4-aminophenol could form from N-phenylhydroxylamine, which in turn forms through reactions b–c″, and/or (ii) 4-aminophenol could form through reactions b–d.
Since, in all experiments of the present work, we never detected N-phenylhydroxylamine in the reaction medium, we assumed that it reacted quickly during the reaction. As a matter of fact, it is reported that some metal catalysts (usually Pd/C, Pt/C, or Ru/C, but it could be possible also the Pd(0) species active in the present work) catalyze the fast reaction of N-phenylhydroxylamine with hydrogen to form aniline together with the 4-aminophenol, via the Bamberger’s rearrangement (Scheme 3, [50,52,74,75,76,77,78]). By considering that it is plausible also the formation in situ of hydrogen from CO and H2O, through the Pd(II)-catalyzed water gas shift reaction [79,80,81], we have carried out some additional experiments to test such a pathway.
At first, N-phenylhydroxylamine was used as feedstock instead of nitrobenzene. It was verified that aniline and 4-aminophenol were not formed under the reaction conditions (H2O/AcOH = 50/50 mol/mol, 403 K, 3 h). In the second set of experiments, hydrogen (up to 1.0 MPa) was added to the reaction mixture, starting both from nitrobenzene and N-phenylhydroxylamine. Also in these cases, 4-aminophenol was not detected in the reaction medium at the end of the reaction.
Therefore, it has been hypothesized that 4-aminophenol forms through the pathway c–d, which supposes the formation of Pd-species (3 and 3″, Scheme 2) similar to those invoked in literature for the mechanism of the Bamberger’s rearrangement [50,52,74,75,76,77,78]. Such point, however, needs further studies, which are in progress.

4. Conclusions

The reductive carbonylation of nitrobenzene, by using the [PdCl2(dppb)] complex as a catalyst precursor, leads to a mixture of acetaminophen and N-phenylacetamide in one pot when carried out in dilute acetic acid as a solvent. Although both products are interesting targets for the pharmaceutical industry, we can produce acetaminophen in one pot, choosing the most suitable reaction conditions (for instance, in H2O/AcOH = 50/50 mol/mol and at 403 K, 5 h of reaction it has been obtained acetaminophen, with 85% selectivity and 100% conversion of nitrobenzene).
We have pointed out that the selectivity towards A (4-aminophenol and acetaminophen) increases by increasing the amount of H2O but, on the other hand, the high percent of H2O favors 4-aminophenol rather than acetaminophen. Moreover, by increasing the temperature and the reaction time, it is possible to favor both the selectivity towards A and the acetylation to acetaminophen (100% at 5 h).

Author Contributions

Conceptualization, M.C. and A.V.; Methodology M.C., L.R. and A.V.; Data curation, M.C. and A.V.; Writing—review and editing, A.V. and L.R.; Supervision, A.V. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding. This work was supported by the Department of Molecular Sciences and Nanosystems of Ca’ Foscari University of Venice.

Data Availability Statement

The data presented in this study are available in the main text.

Acknowledgments

The authors are grateful to Claudio Tortato for his support in the HPLC characterization of the products.

Conflicts of Interest

The authors declare no conflict of interest.

References

  1. Ellis, F. Paracetamol, a Curriculum Resource; Osborne, C., Pack, M., Eds.; RSC: London, UK, 2002. [Google Scholar]
  2. Ogemdi, I.K. A Review on the Properties and Uses of Paracetamol. Int. J. Pharm. Chem. 2019, 5, 31–35. [Google Scholar] [CrossRef]
  3. Eynde, J.J.V. How Efficient Is My (Medicinal) Chemistry? Pharmaceuticals 2016, 9, 26. [Google Scholar] [CrossRef] [PubMed]
  4. Saragiotto, B.T.; Shaheed, C.A.; Maher, C.G. Paracetamol for pain in adults. BMJ 2019, 367, l6693. [Google Scholar] [CrossRef] [PubMed]
  5. Friderichs, E.; Christoph, T.; Buschmann, H. Analgesics and Antipyretics. In Ullmann’s Encyclopedia of Industrial Chemistry; Wiley-VCH Verlag GmbH & Co. KGaA: Hoboken, NJ, USA, 2007; pp. 1–97. [Google Scholar] [CrossRef]
  6. Anantharaman, P.N. p-acetamol from phenol via p-nitrophenol. Bull. Electrochem. 1985, 1, 471. [Google Scholar]
  7. Davenport, K.G.; Hilton, C.B. Process for Producing N-acyl-hydroxy Aromatic Amines. U.S. Patent 4,524,217, 18 June 1985. [Google Scholar]
  8. Fritch, J.R.; Fruchey, S.O.; Horlenko, T.; Aguilar, D.A.; Hilton, C.B.; Snyder, P.S.; Seeliger, W.J. Production of acetaminophen. U.S. Patent 5,155,273, 13 October 1992. [Google Scholar]
  9. Du, Y.; Chen, H.; Chen, R.; Xu, N. Synthesis of p-aminophenol from p-nitrophenol over nano-sized nickel catalysts. Appl. Catal. A Gen. 2004, 277, 259–264. [Google Scholar] [CrossRef]
  10. Rode, C.V.; Vaidya, M.J.; Chaudhari, R.V. Synthesis of p-Aminophenol by Catalytic Hydrogenation of Nitrobenzene. Org. Proc. Res. Dev. 1999, 3, 465–470. [Google Scholar] [CrossRef]
  11. Min, K.; Choi, J.; Chung, Y.; Ahn, W.; Ryoo, R.; Lim, P.K. p-Aminophenol synthesis in an organic/aqueous system using Pt supported on mesoporous carbons. Appl. Catal. A Gen. 2008, 337, 97–104. [Google Scholar] [CrossRef]
  12. Wang, Y.; Wang, S.; Li, F. Process for Synthesizing Paracetamol. CN Patent 1569819(A), 26 January 2005. [Google Scholar]
  13. Takasaki, M.; Motoyama, Y.; Higashi, K.; Yoon, S.-H.; Mochida, I.; Nagashima, H. Chemoselective Hydrogenation of Nitroarenes with Carbon Nanofiber-Supported Platinum and Palladium Nanoparticles. Org. Lett. 2008, 10, 1601–1604. [Google Scholar] [CrossRef]
  14. Li, M.; Hu, L.; Cao, X.; Hong, H.; Lu, J.; Gu, H. Direct Hydrogenation of Nitroaromatics and One-Pot Amidation with Carboxylic Acids over Platinum Nanowires. Chem. Eur. J. 2011, 17, 2763–2768. [Google Scholar] [CrossRef]
  15. Xu, K.; Zhang, Y.; Chen, X.; Huang, L.; Zhang, R.; Huang, J. Convenient and Selective Hydrogenation of Nitro Aromatics with a Platinum Nanocatalyst under Ambient Pressure. Adv. Synth. Catal. 2011, 353, 1260–1264. [Google Scholar] [CrossRef]
  16. Cárdenas-Lizana, F.; Berguerand, C.; Yuranov, I.; Kiwi-Minsker, L. Chemoselective hydrogenation of nitroarenes: Boosting nanoparticle efficiency by confinement within highly porous polymeric framework. J. Catal. 2013, 301, 103–111. [Google Scholar] [CrossRef]
  17. Anastas, P.T.; Zimmerman, J.B. Peer Reviewed: Design Through the 12 Principles of Green Engineering. Environ. Sci. Technol. 2003, 37, 94A–101A. [Google Scholar] [CrossRef] [PubMed]
  18. Abraham, M.A.; Nguyen, N. Green engineering: Defining the principles”—Results from the Sandestin conference. Environ. Prog. 2003, 22, 233–236. [Google Scholar] [CrossRef]
  19. Mitchell, S. Kirk-Othmer Encyclopedia of Chemical Technology, 4th ed.; Wiley-Interscience: New York, NY, USA, 1992; Volume 2, pp. 481–580. [Google Scholar]
  20. Juang, T.M.; Hwang, J.C.; Ho, H.O.; Chen, C.Y. Selectivity in the Phase Transfer Catalytic Hydrogenation of Nitrobenzene by Transition VIII Metals. J. Chin. Chem. Soc. 1988, 35, 135. [Google Scholar] [CrossRef]
  21. Anastas, P.T.; Williamson, T.C. (Eds.) Green Chemistry: Frontiers in Chemical Synthesis and Processes; Oxford Univ. Press: Oxford, UK, 1998. [Google Scholar]
  22. Sheldon, R.A. Industrial Environmental Chemistry; Sawyer, D.T., Martell,, A.E., Eds.; Plenum: New York, NY, USA, 1992; pp. 99–119. [Google Scholar]
  23. Busacca, C.A.; Fandrick, D.R.; Song, J.J.; Senanayake, C.H. The Growing Impact of Catalysis in the Pharmaceutical Industry. Adv. Synth. Catal. 2011, 353, 1825–1864. [Google Scholar] [CrossRef]
  24. Fritch, J.R.; Fruchey, O.S.; Horlenko, T. Production of Acetaminophen. U.S. Patent 4,954,652, 4 September 1990. [Google Scholar]
  25. Beckmann, E. Zur Kenntniss der Isonitrosoverbindungen. Ber. Dtsch. Chem. Ges. 1886, 19, 988–993. [Google Scholar] [CrossRef]
  26. Donaruma, L.G.; Heldt, W.Z. The Beckmann Rearrangement. Org. React. 1960, 11, 1–156. [Google Scholar]
  27. Gawley, R.E. The Beckmann Reactions: Rearrangement, Elimination-Additions, Fragmentations, and Rearrangement-Cyclizations. Org. React. 1988, 35, 14–24. [Google Scholar]
  28. Rode, C.V.; Vaidya, M.J.; Jaganathan, R.; Chaudhari, R.V. Hydrogenation of nitrobenzene to p-aminophenol in a four-phase reactor: Reaction kinetics and mass transfer effects. Chem. Eng. Sci. 2001, 56, 1299–1304. [Google Scholar] [CrossRef]
  29. Nadgeri, J.M.; Biradar, N.S.; Patil, P.B.; Jadkar, S.T.; Garade, A.C.; Rode, C.V. Control of Competing Hydrogenation of Phenylhydroxylamine to Aniline in a Single-Step Hydrogenation of Nitrobenzene to p-Aminophenol. Ind. Eng. Chem. Res. 2011, 50, 5478–5484. [Google Scholar] [CrossRef]
  30. Quartarone, G.; Rancan, E.; Ronchin, L.; Vavasori, A. Beckmann rearrangement of acetophenone oximes to the corresponding amides organo-catalyzed by trifluoroacetic acid for sustainable NSAIDs synthesis. Appl. Cat. A Gen. 2014, 472, 167–177. [Google Scholar] [CrossRef]
  31. Chaudhari, R.V.; Divekar, S.S.; Vaidya, M.J.; Rode, C.V. Single Step Process for the Preparation of P-aminophenol. U.S. Patent 6,028,227, 22 February 2000. [Google Scholar]
  32. Komatsu, T.; Hirose, T. Gas phase synthesis of para-aminophenol from nitrobenzene on Pt/zeolite catalysts. Appl. Catal. A Gen. 2004, 276, 95–102. [Google Scholar] [CrossRef]
  33. Wang, S.; Ma, Y.; Wang, Y.; Xue, W.; Zhao, X. Synthesis of p-aminophenol from the hydrogenation of nitrobenzene over metal–solid acid bifunctional catalyst. J. Chem. Technol. Biotechnol. 2008, 83, 1466–1471. [Google Scholar] [CrossRef]
  34. Liu, P.; Hu, Y.; Ni, M.; You, K.; Luo, H. Liquid Phase Hydrogenation of Nitrobenzene to Para-Aminophenol over Pt/ZrO2 Catalyst and SO4 2−/ZrO2–Al2O3 Solid Acid. Catal. Lett. 2010, 140, 65–68. [Google Scholar] [CrossRef]
  35. Wang, S.; Wang, Y.; Gao, Y.; Zhao, X. Preparation of SAPO-5 and Its Catalytic Synthesis of p-Aminophenol. Chin. J. Catal. 2010, 311, 637–644. [Google Scholar] [CrossRef]
  36. Deshpande, A.; Figueras, F.; Kantam, M.L.; Ratnam, K.J.; Reddy, R.S.; Sekhar, N.S. Environmentally friendly hydrogenation of nitrobenzene to p-aminophenol using heterogeneous catalysts. J. Catal. 2010, 275, 250–256. [Google Scholar] [CrossRef]
  37. Wang, S.; Jin, Y.; He, B.; Wang, Y.; Zhao, X. Synthesis of bifunctional Pt/MgAPO-5 catalysts and their catalytic performance in the hydrogenation of nitrobenzene to p-aminophenol. Sci. China Chem. 2010, 53, 1514–1519. [Google Scholar] [CrossRef]
  38. Aricò, F.; Quartarone, G.; Rancan, E.; Ronchin, L.; Tundo, P.; Vavasori, A. One-pot oximation–Beckmann rearrangement of ketones and aldehydes to amides of industrial interest: Acetanilide, caprolactam and acetaminophen. Cat. Commun. 2014, 49, 47–51. [Google Scholar] [CrossRef]
  39. Rancan, E.; Aricò, F.; Quartarone, G.; Ronchin, L.; Tundo, P.; Vavasori, A. Self-catalyzed direct amidation of ketones: A sustainable procedure for acetaminophen synthesis. Cat. Commun. 2014, 54, 11–16. [Google Scholar] [CrossRef]
  40. Joncour, R.; Duguet, N.; Métay, E.; Ferreira, A.; Lemaire, M. Amidation of phenol derivatives: A direct synthesis of paracetamol (acetaminophen) from hydroquinone. Green Chem. 2014, 16, 2997–3002. [Google Scholar] [CrossRef]
  41. Bhattacharya, A.; Purohit, V.C.; Suarez, V.; Tichkule, R.; Parmer, G.; Rinaldi, F. One-step reductive amidation of nitro arenes: Application in the synthesis of Acetaminophen™. Tetrahedron Lett. 2006, 47, 1861–1864. [Google Scholar] [CrossRef]
  42. Rylander, P.N. Hydrogenation Methods; Academic Press: New York, NY, USA, 1985. [Google Scholar]
  43. Gao, Y.; Wang, F.D.; Liao, S.J.; Yu, D.R. Selective hydrogenation of nitrobenzene top-Aminophenol by the polymer-supported palladium-based mono- and bimetallic catalyst. React. Kinet. Catal. Lett. 1998, 64, 351–357. [Google Scholar] [CrossRef]
  44. Wang, S.F.; He, B.B.; Wang, Y.J.; Zhao, X.Q. MgAPO-5-supported Pt–Pb-based novel catalyst for the hydrogenation of nitrobenzene to p-aminophenol. Catal. Commun. 2012, 24, 109–113. [Google Scholar] [CrossRef]
  45. Quartarone, G.; Ronchin, L.; Tosetto, A.; Vavasori, A. New insight on the mechanism of the catalytic hydrogenation of nitrobenzene to 4-aminophenol in CH3CN–H2O–CF3COOH as a reusable solvent system. Hydrogenation of nitrobenzene catalyzed by precious metals supported on carbon. Appl. Cat. A Gen. 2014, 475, 169–178. [Google Scholar] [CrossRef]
  46. Zou, L.Y.; Cui, Y.Y.; Dai, W.L. Highly Efficient Au/TiO2 Catalyst for One-pot Conversion of Nitrobenzene to p-Aminophenol in Water Media. Chin. J. Chem. 2014, 32, 257–262. [Google Scholar] [CrossRef]
  47. Tanielyan, S.K.; Nair, J.J.; Marin, N.; Alvez, G.; McNair, R.J.; Wang, D.; Augustine, R.L. Hydrogenation of Nitrobenzene to 4-Aminophenol over Supported Platinum Catalysts. Org. Process Res. Dev. 2007, 11, 681–688. [Google Scholar] [CrossRef]
  48. Serrà, A.; Alcobé, X.; Sort, J.; Nogués, J.; Vallés, E. Highly efficient electrochemical and chemical hydrogenation of 4-nitrophenol using recyclable narrow mesoporous magnetic CoPt nanowires. J. Mater. Chem. A 2016, 4, 15676–15687. [Google Scholar] [CrossRef]
  49. Joncour, R.; Ferreira, A.; Duguet, N.; Lemaire, M. Preparation of para-Aminophenol from Nitrobenzene through Bamberger Rearrangement Using a Mixture of Heterogeneous and Homogeneous Acid Catalysts. Org. Process Res. Dev. 2018, 22, 312–320. [Google Scholar] [CrossRef]
  50. Bamberger, E. Ueber das Phenylhydroxylamin. Ber. Dtsch. Chem. Ges. 1894, 27, 1548–1557. [Google Scholar] [CrossRef]
  51. Chandrashekha, V.R.; Manisha, J.V.; Chaudhari, R.V. Single Step Hydrogenation of Nitrobenzene to P-aminophenol. U.S. Patent 6,403,833 B1, 11 June 2002. [Google Scholar]
  52. De Fonzo, N.; Quartarone, G.; Ronchin, L.; Tortato, C.; Vavasori, A. Kinetics and mechanistic study of the Bamberger rearrangement of N-phenylhydroxylamine to 4-aminophenol in acetonitrile-trifluoroacetic acid: A substrate acid complex as para selectivity driver. App. Catal. A Gen. 2016, 516, 58–69. [Google Scholar] [CrossRef]
  53. Olariu, T.; Suta, L.M.; Popoiu, C.; Ledeti, I.V.; Simu, G.M.; Balint, G.S. Fulias, Alternative Synthesis of Paracetamol and Aspirin Under Non-conventional Conditions. Rev. Chim. 2014, 65, 633–635. [Google Scholar]
  54. Mane, S.N.; Gadalkar, S.M.; Rathod, V.K. Intensification of paracetamol (acetaminophen) synthesis from hydroquinone using ultrasound. Ultrasonics–Sonochemistry 2018, 49, 106–110. [Google Scholar] [CrossRef]
  55. Jung, S.; Kawashima, Y.; Noguchi, T.; Imai, N. Synthesis of Acetaminophen Analogues Containing α-Amino Acids and Fatty Acids for Inhibiting Hepatotoxicity. Synthesis 2019, 51, 3683–3696. [Google Scholar] [CrossRef]
  56. Ammin, M.; Iqbal, M.S. Solvent Free Synthesis of Acetaminophen. U.S. Patent 9,006,488 B1, 14 April 2015. [Google Scholar]
  57. Corma, A.; Concepción, P.; Serna, P. A Different Reaction Pathway for the Reduction of Aromatic Nitro Compounds on Gold Catalysts. Angew. Chem. Int. Ed. 2007, 46, 7266–7269. [Google Scholar] [CrossRef]
  58. Zhao, R.; Tan, C.; Xie, Y.; Gao, C.; Liu, H.; Jiang, Y. One step synthesis of azo compounds from nitroaromatics and anilines. Tetrahedron Lett. 2011, 52, 3805–3809. [Google Scholar] [CrossRef]
  59. Wehman, P.; Dol, G.C.; Moorman, E.R.; Kamer, P.C.J.; van Leeuwen, P.W.N.M.; Fraanje, J.; Goubitz, K. Ligand Effects in the Palladium-Catalyzed Reductive Carbonylation of Nitrobenzene. Organometallics 1994, 13, 4856–4869. [Google Scholar] [CrossRef]
  60. Wehman, P.; Kaasjager, V.E.; de Lange, W.G.J.; Hartl, F.; Kamer, P.C.J.; van Leeuwen, P.W.N.M.; Fraanje, J.; Goubitz, K. Subtle Balance between Various Phenanthroline Ligands and Anions in the Palladium-Catalyzed Reductive Carbonylation of Nitrobenzene. Organometallics 1995, 14, 3751–3761. [Google Scholar] [CrossRef]
  61. Bolzacchini, E.; Lucini, R.; Meinardi, S.; Orlandi, M.; Rindone, B. Effect of a proximal substituent on the triruthenium dodecacarbonyl-catalyzed reductive carbonylation of nitroarenes. J. Mol. Catal. A Chem. 1996, 110, 227–233. [Google Scholar] [CrossRef]
  62. Macho, V.; Kralik, M.; Halmo, F. New catalytic system of N,N′-diphenylurea synthesis from nitrobenzene, carbon monoxide and water or aniline. J. Mol. Catal. A Chem. 1996, 109, 119–125. [Google Scholar] [CrossRef]
  63. Wehman, P.; Borst, L.; Kamer, P.C.J.; van Leeuwen, P.W.N.M. Influence of an aromatic carboxylic acid as cocatalyst in the palladium-catalysed reductive carbonylation of aromatic nitro compounds. J. Mol. Catal. A Chem. 1996, 112, 23–36. [Google Scholar] [CrossRef]
  64. Wehman, P.; Kamer, P.C.J.; van Leeuwen, P.W.N.M. Reductive carbonylation of aromatic dinitro compounds with a palladium(phenanthroline)2(triflate)2 catalyst and an aromatic carboxylic acid as cocatalyst. Chem. Commun. 1996, 217–218. [Google Scholar] [CrossRef]
  65. Ya, Y.; Lu, S. Selenium-catalyzed reductive carbonylation of nitrobenzene with amines as coreagents to give unsymmetric phenylureas. Tetrahedron Lett. 1999, 40, 4845–4846. [Google Scholar] [CrossRef]
  66. Ragaini, F.; Ghitti, A.; Cenini, S. Mechanistic Study of the Ru3(CO)12/Tetraalkylammonium Chloride Catalyzed Carbonylation Reactions of Nitroarenes to Carbamates and Ureas:  A Completely Revised Picture. Organometallics 1999, 18, 4925–4933. [Google Scholar] [CrossRef]
  67. Ragaini, F.; Cenini, S. Mechanistic study of the Ru3(CO)12/chloride catalyzed carbonylation reactions of nitroarenes to carbamates and ureas; the role of the alkylammonium cation. J. Mol. Catal. A Chem. 2000, 161, 31–38. [Google Scholar] [CrossRef]
  68. Ling, G.; Chen, J.Z.; Lu, S.W. Selenium-catalyzed carbonylation of substituted nitrobenzenes with aminomethylpyrimidines as co-reagents to synthesize N-phenyl-N′-methylpyrimidylurea derivatives. J. Mol. Catal. A Chem. 2003, 202, 23–29. [Google Scholar] [CrossRef]
  69. Ragaini, F.; Gasperini, M.; Cenini, S.; Arnera, L.; Caselli, A.; Macchi, P.; Casati, N. Mechanistic Study of the Palladium–Phenanthroline Catalyzed Carbonylation of Nitroarenes and Amines: Palladium–Carbonyl Intermediates and Bifunctional Effects. Chem. Eur. J. 2009, 15, 8064–8077. [Google Scholar] [CrossRef] [PubMed]
  70. Mooibroek, T.J.; Schoon, L.; Bouwman, E.; Drent, E. Carbonylation of Nitrobenzene in Methanol with Palladium Bidentate Phosphane Complexes: An Unexpectedly Complex Network of Catalytic Reactions, Centred around a Pd–imido Intermediate. Chem. Eur. J. 2011, 17, 13318–13333. [Google Scholar] [CrossRef]
  71. Vavasori, A.; Ronchin, L. Phosgene-free synthesis of 1,3-diphenylurea via catalyzed reductive carbonylation of nitrobenzene. Pure Appl. Chem. 2012, 84, 473–484. [Google Scholar] [CrossRef]
  72. Vavasori, A.; Capponi, M.; Ronchin, L. One-pot synthesis of paracetamol via the catalytic reductive carbonylation of nitrobenzene in acetic acid-water as a solvent. Chem. Listy 2012, 106, 1191. [Google Scholar]
  73. van Leeuwen, P.W.N.M.; Kamer, P.C.J.; Reek, J.N.H. The bite angle makes the catalyst. Pure Appl. Chem. 1999, 71, 1443–1452. [Google Scholar] [CrossRef]
  74. Fishbein, J.C.; McClelland, R.A. Halide ion trapping of nitrenium ions formed in the Bamberger rearrangement of N-arylhydroxylamines. Lifetime of the parent phenylnitrenium ion in water. Can. J. Chem. 1996, 74, 1321–1328. [Google Scholar] [CrossRef]
  75. Heller, H.E.; Hughes, E.D.; Ingold, C.K. A New View of the Arylhydroxylamine Rearrangement. Ingold Nat. 1951, 168, 909–910. [Google Scholar] [CrossRef]
  76. Sone, T.; Tokuda, Y.; Sakai, T.; Shinkai, S.; Manabe, O. Kinetics and mechanisms of the Bamberger rearrangement. Part 3. Rearrangement of phenylhydroxylamines to p-aminophenols in aqueous sulphuric acid solutions. J. Chem. Soc. Perkin Trans. 1981, 2, 298–302. [Google Scholar] [CrossRef]
  77. Sone, T.; Hamamoto, K.; Seiji, Y.; Shinkai, S.; Manabe, O. Kinetics and mechanisms of the Bamberger rearrangement. Part 4. Rearrangement of sterically hindered phenylhydroxylamines to 4-aminophenols in aqueous sulphuric acid solution. J. Chem. Soc. Perkin Trans. 1981, 2, 1596–1598. [Google Scholar] [CrossRef]
  78. Kohnstam, G.; Petch, W.A.; Williams, D.L.H. Kinetic substituent and isotope effects in the acid-catalysed rearrangement of N-phenylhydroxylamines. Are nitrenium lons involved? J. Chem. Soc. Perkin Trans. 1984, 2, 423–427. [Google Scholar] [CrossRef]
  79. Vavasori, A.; Dall’Acqua, F.; Cavinato, G.; Toniolo, L. Influence of the operating conditions on the catalytic activity of [PdCl2(dapp)] in the CO–ethene copolymerization in the H2O–CH3COOH as a solvent (dapp = 1,3-bis(di(2-methoxyphenyl)phosphino)propane). J. Mol. Catal. A Chem. 2010, 332, 158–164. [Google Scholar] [CrossRef]
  80. Zudin, V.N.; Ill’inich, G.N.; Likholobov, V.A.; Yermakow, Y.I. New catalyst for the synthesis of dialkyl ketones from olefins, carbon monoxide, and hydrogen. J. Chem. Soc. Chem. Commun. 1984, 545–546. [Google Scholar] [CrossRef]
  81. Zudin, V.N.; Chinakov, V.D.; Nekipelov, V.M.; Rogov, V.A.; Likholobov, V.A.; Yermakow, Y.I. Determination of key intermediates for homogeneous water-gas shift reaction and hydrocarbonylation of ethylene to diethyl ketone catalyzed by the Pd(OAc)2-PPh3-CF3COOH/H2O system. J. Mol. Catal. 1989, 52, 27–48. [Google Scholar] [CrossRef]
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Figure 1. Influence of solvent composition on the conversion. Run conditions: [PdCl2(dppb)] = 1.50 mg (2.48 × 10−3 mmol), nitrobenzene = 0.5 mL (0.600 g, 4.87 mmoli), Vtot = 12 mL, T = 373 K, PCO = 5.0 MPa, reaction time = 3 h.
Figure 1. Influence of solvent composition on the conversion. Run conditions: [PdCl2(dppb)] = 1.50 mg (2.48 × 10−3 mmol), nitrobenzene = 0.5 mL (0.600 g, 4.87 mmoli), Vtot = 12 mL, T = 373 K, PCO = 5.0 MPa, reaction time = 3 h.
Reactions 04 00042 g001
Reactions 04 00042 sch001
Scheme 1. Scheme of the possible products formed during the reductive carbonylation of nitrobenzene in H2O-AcOH as a solvent.
Scheme 1. Scheme of the possible products formed during the reductive carbonylation of nitrobenzene in H2O-AcOH as a solvent.
Reactions 04 00042 sch001
Reactions 04 00042 g002
Figure 2. Influence of temperature on the selectivity to A and to its composition in terms of acetaminophen and 4-aminophenol. Run conditions: [PdCl2(dppb)] = 1.50 mg (2.48 × 10−3 mmol), nitrobenzene = 0.5 mL (0.600 g, 4.87 mmoli), Vtot = 12 mL (H2O/AcOH = 50/50 mol/mol), PCO = 5.0 MPa, reaction time = 3 h.
Figure 2. Influence of temperature on the selectivity to A and to its composition in terms of acetaminophen and 4-aminophenol. Run conditions: [PdCl2(dppb)] = 1.50 mg (2.48 × 10−3 mmol), nitrobenzene = 0.5 mL (0.600 g, 4.87 mmoli), Vtot = 12 mL (H2O/AcOH = 50/50 mol/mol), PCO = 5.0 MPa, reaction time = 3 h.
Reactions 04 00042 g002
Reactions 04 00042 sch002
Scheme 2. Proposed reaction mechanism.
Scheme 2. Proposed reaction mechanism.
Reactions 04 00042 sch002
Reactions 04 00042 sch003
Scheme 3. Formation of 4-aminophenol through Bamberger’s rearrangement.
Scheme 3. Formation of 4-aminophenol through Bamberger’s rearrangement.
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Table 1. Catalytic activity of some Pd(II)–diphosphine complexes.
Table 1. Catalytic activity of some Pd(II)–diphosphine complexes.
EntryCatalystConversionTONSelectivity (mol %)
n° mol * %mol */mol Pd4-AminophenolAcetaminophenAnilineAcetanilideOther
1[PdCl2(dppe)]47815640309
2[PdCl2(dppp)]22432157363012
3[PdCl2(dppb)]601178198332515
4[PdCl2(dppf)]551080167322817
5[PdCl2(Xantphos)]14276157382515
6[Pd(AcO)2(dppe)]23913543309
7[Pd(AcO)2(dppp)]20393146383012
8[Pd(AcO)2(dppb)]581139156392515
9[Pd(AcO)2(dppf)]571119145362817
10[Pd(AcO)2(Xantphos)]15296146402713
Run conditions: Pd(II) = 2.48 × 10−3 mmol, nitrobenzene = 0.5 mL (0.600 g, 4.87 mmoli), Vtot = 12 mL (H2O/AcOH = 30/70, mol/mol), T = 373 K, PCO = 5.0 MPa, reaction time = 3 h. * moles of NB converted.
Table 2. Influence of solvent composition on conversion and selectivity.
Table 2. Influence of solvent composition on conversion and selectivity.
EntryH2O (AcOH)
mol %		NB Conversion
mol %		TON mol/molSelectivity (mol %)
A
B
C
D
17 (93)39765892n.d.n.d.
214 (86)4486318802n.d.
330 (70)6011772758123
450 (50)75147234421212
560 (40)99194240301812
Run conditions: [PdCl2(dppb)] = 1.50 mg (2.48 × 10−3 mmol), nitrobenzene = 0.5 mL (0.600 g, 4.87 mmoli), Vtot = 12 mL, T = 373 K, PCO = 5.0 MPa, reaction time = 3 h, (n.d. = not detected).
Table 3. Influence of the solvent on composition of A and B.
Table 3. Influence of the solvent on composition of A and B.
EntryH2O (AcOH)Sel. to A *Composition of A (mol %)Sel. to B * (mol %)Composition of B (mol %)
n°mol %mol %4-AminophenolAcetaminophen AnilineAcetaniline
17 (93)8991928218
214 (86)187030805743
330 (70)276040584753
450 (50)344258423367
560 (40)40287230991
Run conditions: * see Table 2.
Table 4. Influence of the pressure on the conversion and selectivity.
Table 4. Influence of the pressure on the conversion and selectivity.
PNB ConversionSelectivity (mol %)
MPamol %ABCD
2.553652078
4.075642565
5.0996519115
6.01006720112
Run conditions: [PdCl2(dppb)] = 1.50 mg (2.48 × 10−3 mmol), nitrobenzene = 0.5 mL (0.600 g, 4.87 mmoli), Vtot = 12 mL, (H2O/AcOH = 50/50 mol/mol), T = 393 K, reaction time = 3 h.
Table 5. Influence of the temperature on the conversion and selectivity.
Table 5. Influence of the temperature on the conversion and selectivity.
TNB ConversionSelectivity

K
mol %		A
(mol %)		B
(mol %)		C
(mol %)		D
(mol %)
333181764712
343241960912
3737534451011
393996519115
40310085852
41390817102
43370807112
Run conditions: [PdCl2(dppb)] = 1.50 mg (2.48 × 10−3 mmol), nitrobenzene = 0.5 mL (0.600 g, 4.87 mmoli), Vtot = 12 mL, (H2O/AcOH = 50/50 mol/mol), PCO = 5.0 MPa, reaction time = 3 h.
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Vavasori, A.; Capponi, M.; Ronchin, L. A New Pd-Based Catalytic System for the Reductive Carbonylation of Nitrobenzene to Form N-(4-hydroxyphenyl)acetamide Selectively in One Pot. Reactions 2023, 4, 725-736. https://doi.org/10.3390/reactions4040042

AMA Style

Vavasori A, Capponi M, Ronchin L. A New Pd-Based Catalytic System for the Reductive Carbonylation of Nitrobenzene to Form N-(4-hydroxyphenyl)acetamide Selectively in One Pot. Reactions. 2023; 4(4):725-736. https://doi.org/10.3390/reactions4040042

Chicago/Turabian Style

Vavasori, Andrea, Marco Capponi, and Lucio Ronchin. 2023. "A New Pd-Based Catalytic System for the Reductive Carbonylation of Nitrobenzene to Form N-(4-hydroxyphenyl)acetamide Selectively in One Pot" Reactions 4, no. 4: 725-736. https://doi.org/10.3390/reactions4040042

APA Style

Vavasori, A., Capponi, M., & Ronchin, L. (2023). A New Pd-Based Catalytic System for the Reductive Carbonylation of Nitrobenzene to Form N-(4-hydroxyphenyl)acetamide Selectively in One Pot. Reactions, 4(4), 725-736. https://doi.org/10.3390/reactions4040042

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