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Till now I could only find one laboratory preparation of aniline, i.e. reducing nitrobenzene with $\ce{Sn}$ and concentrated $\ce{HCl}$. I'm confused if Hofmann degradation is only commercial. I'd like to know if there are other processes to prepare aniline in laboratory.

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    $\begingroup$ Catalytic hydrogenation of nitrobenzene over Pd/Pt/Ni catalysts $\endgroup$ – Waylander Aug 22 '20 at 19:09
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    $\begingroup$ Why would anybody prepare aniline in lab? $\endgroup$ – Mithoron Aug 22 '20 at 19:09
  • $\begingroup$ Is Hoffmann Bromamide reaction only commercial or a laboratory method? I only want to know, I don't perform these experiments so don't ask me why to prepare in laboratory or whatnot. $\endgroup$ – Aksh Sarma Aug 23 '20 at 3:30
  • $\begingroup$ Check this 2009 paper which gives loads of palladium catalyzed and copper catalyzed reactions. $\endgroup$ – Nilay Ghosh Aug 23 '20 at 5:39
  • $\begingroup$ @AkshSarma Hoffman Bromamide is pointless from a synthesis perspective; if you have to prepare aniline, it is much easier/cheaper to use nitrobenzene as a raw material than Acetanilide. Chances are if you have acetanilide, you will also have aniline. $\endgroup$ – Aniruddha Deb Aug 23 '20 at 7:08
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It is true that until recently, the syntheses of primary anilines mostly rely on the reduction of corresponding nitroarenes. However, recent publications allow the synthesis of primary anilines or their derivatives in laboratory.

One such method is Buchwald–Hartwig amination:

Buchwald–Hartwig amination

The palladium-catalyzed cross-coupling of amines and aryl (pseudo)halides, now commonly known as the Buchwald–Hartwig amination, was first reported 25 years ago. Since the simultaneous breakthrough reports of Buchwald and Hartwig in 1995, this reaction has transformed the way synthetic chemists think about synthesizing aromatic amines... (Ref.1):

Progress of Buchwald–Hartwig amination through recent years

A continuous process for Buchwald–Hartwig amination in different scale synthesis has also been introduced recently (Ref.2). Further, a version of Buchwald–Hartwig amination for the preparation of primary arylamines has been introduced recently as a general method (Ref.3):

Preparation of primary arylamines

The importance of the method is reflected by the development of a synthetic route to manufacture the drug candidate AMG 925 on kilogram scale using Buchwald–Hartwig amination (Ref.4):

synthetic route to manufacture intermediate for AMG 925

Another amine synthetic method not following nitro reduction is Ullmann amine synthesis and its variations (Ref.5 and references therein):

Ullmann amine synthesis and its variations

In addition, secondary or tertiary amine can be prepared using Chan-Lam coupling reaction. For example see following reaction (Ref.6):

Chan-Lam coupling reaction

Other than using aryl halides, there is an another method to convert phenol derivatives to anilines. One such example describes a direct conversion of phenols into primary anilines with hydrazine catalyzed by palladium (Ref.7):

Direct conversion of phenols into primary anilines


References:

  1. Paola A. Forero-Cortés, Alexander M. Haydl, "The 25th Anniversary of the Buchwald–Hartwig Amination: Development, Applications, and Outlook," Org. Process Res. Dev. 2019, 23(8), 1478–1483 (https://doi.org/10.1021/acs.oprd.9b00161).
  2. Sebastian Falß, Giovanna Tomaiuolo, Antonio Perazzo, Paul Hodgson, Polina Yaseneva, Jacek Zakrzewski, Stefano Guido, Alexei Lapkin, Robert Woodward, Rebecca E. Meadows, "A Continuous Process for Buchwald–Hartwig Amination at Micro-, Lab-, and Mesoscale Using a Novel Reactor Concept," Org. Process Res. Dev. 2016, 20(2), 558–567 (https://doi.org/10.1021/acs.oprd.5b00350).
  3. Giang D. Vo, John F. Hartwig, "Palladium-Catalyzed Coupling of Ammonia with Aryl Chlorides, Bromides, Iodides, and Sulfonates: A General Method for the Preparation of Primary Arylamines," J. Am. Chem. Soc. 2009, 131(31), 11049–11061 (https://doi.org/10.1021/ja903049z).
  4. Caroline Affouard, Richard D. Crockett, Khalid Diker, Robert P. Farrell, Gilles Gorins, John R. Huckins, Seb Caille, "Multi-Kilo Delivery of AMG 925 Featuring a Buchwald–Hartwig Amination and Processing with Insoluble Synthetic Intermediates," Org. Process Res. Dev. 2015, 19(3), 476–485 (https://doi.org/10.1021/op500367p).
  5. Andrea Francesca Quivelli, Paola Vitale, Filippo Maria Perna, Vito Capriati, "Reshaping Ullmann Amine Synthesis in Deep Eutectic Solvents: A Mild Approach for Cu-Catalyzed C–N Coupling Reactions With No Additional Ligands," Frontiers in Chemistry 2019, 7, Article 723 (14 pages) (https://doi.org/10.3389/fchem.2019.00723)(Full Paper).
  6. Carolin Fischer, Burkhard Koenig, "Palladium- and copper-mediated N-aryl bond formation reactions for the synthesis of biological active compounds," Beilstein J. Org. Chem. 2011, 7, 59-74 (https://doi.org/10.3762/bjoc.7.10)(Full Paper).
  7. Zihang Qiu, Leiyang Lv, Jianbin Li, Chen-Chen Li, Chao-Jun Li, "Direct conversion of phenols into primary anilines with hydrazine catalyzed by palladium," Chem. Sci. 2019, 10(18), 4775-4781 (https://doi.org/10.1039/C9SC00595A)(Full Paper).
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