Categories: C-N Bond Formation > Amines >
Synthesis of anilines
A general and practical aryl amination of aryl chlorides with aqueous or gaseous ammonia, CuI as the catalyst, and bisaryl oxalic diamides as the ligands proceeds at 105-120 °C to provide a diverse set of primary (hetero)aryl amines in high yields with various functional groups.
M. Fan, W. Zhou, Y. Jiang, D. Ma, Org. Lett., 2015, 17, 5934-5937.
CuI/4-hydroxy-l-proline-catalyzed coupling of aryl bromides and N-Boc hydrazine takes place in DMSO to give N-aryl hydrazides. When aryl iodides are employed, no ligand is required. Under the catalysis of CuI/4-hydroxy-l-proline, the coupling reaction of aqueous ammonia with aryl bromides proceeds smoothly to afford primary arylamines.
L. Jiang, X. Lu, H. Zhang, Y. Jiang, D. Ma, J. Org. Chem., 2009, 74, 4542-4546.
CuI-nanoparticles catalyze a selective synthesis of phenols, anilines, and thiophenols from aryl halides in the absence of both ligands and organic solvents. Anilines were formed selectively with ammonia competing with hydroxylation and thiophenols were generated selectively with sulfur powder after subsequent reduction competing with hydroxylation and amination.
H.-J. Xu, Y.-F. Liang, Z.-Y. Cai, H.-X. Qi, C.-Y. Yang, Y.-S. Feng, J. Org. Chem., 2011, 76, 2296-2300.
LiN(SiMe3)2, Ph3SiNH2, and LiNH2 can be be used as ammonia equivalents for the Pd-catalyzed coupling of aryl halides to provide simple anilines, including ortho-substituted ones, as well as di- and triarylamines.
X. Huang, S. L. Buchwald, Org. Lett., 2001, 3, 3417-3419.
The use of lithium bis(trimethylsilyl)amide (LiN(SiMe3)2) enables a simple, palladium-catalyzed conversion of aryl halides to the parent anilines. The reaction is catalyzed by Pd(dba)2 and P(t-Bu)3 and can be run with as little as 0.2 mol % of catalyst.
S. Lee, M. Jĝrgensen, J. F. Hartwig, Org. Lett., 2001, 3, 2729-2732.
A complex generated from Pd[P(o-tol)3]2 and the alkylbisphosphine CyPF-t-Bu is a highly active and selective catalyst for the coupling of ammonia with aryl chlorides, bromides, iodides, and sulfonates. The couplings with this catalyst conducted with a solution of ammonia in dioxane form primary arylamines from various aryl electrophiles in high yields.
G. D. Vo, J. F. Hartwig, J. Am. Chem. Soc., 2009, 131, 11049-11061.
A phosphetane-based catalyst operating within PIII/PV=O redox cycling is able to capture HNO, generated in situ by Nef decomposition of 2-nitropropane, to selectively furnish versatile primary arylamines from arylboronic acid substrates with the preservation of otherwise reactive functional groups.
S. Y. Hong, A. T. Radosevich, J. Am. Chem. Soc., 2022, 144, 8902-8907.
Various anilines are prepared by treatment of functionalized arylboronic acids with H2N-OSO3H (HSA) as a common, inexpensive source of electrophilic nitrogen, under basic aqueous conditions. Electron-rich substrates are found to be the most reactive by this method, whereas highly electron-deficient substrates must be converted at reflux. Sterically hindered substrates appear to be equally effective compared to unhindered ones.
S. Voth, J. W. Hollett, J. A. McCubbin, J. Org. Chem., 2015, 80, 2545-2553.
A transition-metal-free synthesis of a series of primary arylamines from potassium aryltrifluoroborates and phenylboronic acids uses hydroxylamine-O-sulfonic acid as a mild, inexpensive source of nitrogen in cooperation with aqueous sodium hydroxide in acetonitrile. Both a sonication and a microwave-assisted method were developed.
D. Kuik, J. A. McCubbin, G. K. Tranmer, Synthesis, 2017, 49, 2555-2561.
An efficient, metal and base-free, chemoselective reaction of boronic acids with cyanamidyl/arylcyanamidyl radicals provides primary aryl-, heteroaryl-, and alkyl amines at ambient temperature within 1 h. The reaction is mediated by PIFA and NBS.
N. Chatterjee, M. Arfeen, P. V. Bharatam, A. Goswami, J. Org. Chem., 2016, 81, 5120-5127.
A palladium-catalyzed coupling of aryl chlorides with ammonia and gaseous amines as their ammonium salts provides monoarylated products with high selectivity. The resting state for reactions of aryl chlorides is different from the resting state for reactions of aryl bromides, and this change in resting states is proposed to account for a difference in selectivities for reactions of the two haloarenes.
R. A. Green, J. F. Hartwig, Org. Lett., 2014, 16, 4388-4391.
In a Pd-catalyzed arylation of ammonia with a wide range of aryl and heteroaryl halides, excellent selectivity for monoarylation was achieved under mild conditions or at rt by the use of bulky biarylphosphine ligands as well as their corresponding aminobiphenyl palladacycle precatalysts. As this process requires neither the use of a glovebox nor high pressures of ammonia, it should be widely applicable.
C. W. Cheung, D. S. Surry, S. L. Buchwald, Org. Lett., 2013, 15, 3734-3737.
Magnetically separable CuFe2O4 nanoparticles in a poly(ethylene glycol) medium are an inexpensive, nontoxic, environmentally benign, and recyclable system for the amination of various aryl iodides with aqueous ammonia to afford the corresponding aryl amines in good yields. The catalytic system was recycled five times with consistent activity.
A. S. Kumar, T. Ramani, B. Sreedhar, Synlett, 2013, 24, 843-846.
An efficient, fast and selective electrosynthesis of phenols and anilines from arylboronic acids in aqueous ammonia is achieved in an undivided cell. By simply changing the concentration of aqueous ammonia and the anode potential, good yields of phenols and anilines can be obtained chemoselectively.
H.-L. Qi, D.-S. Chen, J.-S. Ye, J.-M. Huang, J. Org. Chem., 2013, 78, 7482-7487.
Zn[N(SiMe3)2]2 is a mild ammonia equivalent and base for the palladium-catalyzed amination of aryl halides and triflates. The combination of Zn[N(SiMe3)2]2 and LiCl coupled with aryl halides containing base-sensitive functionality in high yields.
D.-Y. Lee, J. F. Hartwig, Org. Lett., 2005, 7, 1169-1172.
A metal-free synthesis of primary aromatic amines from arylboronic acids affords structurally diverse primary arylamines in good chemical yields, including various halogenated primary anilines. The reaction is operationally simple, requires only a slight excess of aminating agent, proceeds under neutral or basic conditions, and can be scaled up to provide multigram quantities of anilines.
C. Zhu, G. Li, D. H. Ess, J. R. Falck, L. Kürti, J. Am. Chem. Soc., 2012, 134, 18253-18256.
The direct amination of alkyl and aryl pinacol boronates with lithiated methoxyamine provides aliphatic and aromatic amines, stereospecifically, and without preactivation of the boronate substrate.
S. N. Mlynarski, A. S. Karns, J. P. Morken, J. Am. Chem. Soc., 2012, 134, 16449-16451.
A facile and practical copper powder-catalyzed Ullmann amination of aryl halides with aqueous methylamine and other aliphatic primary amines under organic solvent- and ligand-free condition at 100°C and in air gave N-arylamines as sole products in very good yields. The presence of a small amount of air is essential. Secondary amines and aniline are not reactive. Sensitive substituents are tolerated.
J. Jiao, X.-R. Zhang, N.-H. Chang, J. Wang, J.-F. Wei, X.-Y. Shi, Z.-G. Chen, J. Org. Chem., 2011, 76, 1180-1183.
Amination Reactions of Aryl Halides with Nitrogen-Containing Reagents Mediated by Palladium/Imidazolium Salt Systems
G. A. Grasa, M. S. Viciu, J. Huang, S. P. Nolan, J. Org. Chem., 2001, 66, 7714-7722.
A metal-free synthesis of arylamines via the direct amination of phenols using easily accessible aminating reagents provides a versatile route to a broad range of arylamines with various functionalities in good yield. By using a two-step route of amination and oxidative coupling reaction, three naturally occurring carbazole alkaloids are synthesized from commercially available phenols: murrayafoline A, mukonine, and clausenine.
J. Yu, Y. Wang, P. Zhang, J. Wu, Synlett, 2013, 24, 1448-1454.
The reaction of di-tert-butyl dicarbonate or a chloroformate and sodium azide with an aromatic carboxylic acid produces the corresponding acyl azide. The acyl azide undergoes a Curtius rearrangement to form an isocyanate derivative which is trapped either by an alkoxide or by an amine to form the aromatic carbamate or urea.
H. Lebel, O. Leogane, Org. Lett., 2006, 8, 5717-5720.
An oxime reagent as an amino group source achieves a direct conversion from acetyl arenes and alkanes to primary amines with C-C bond cleavage via domino transoximation/Beckmann rearrangement/Pinner reaction. The method was also applied to the synthesis of γ-aminobutyric acids, such as rolipram and baclophen.
K. Hyodo, G. Hasegawa, H. Maki, K. Uchida, Org. Lett., 2019, 21, 2818-2822.
The use of a Pd/C-ethylene system enables a synthesis of anilines and indoles from cyclohexanones in the presence of NH4OAc. Hydrogen transfer between cyclohexanone and ethylene generates the desired products. The reaction tolerates a variety of substitutions on the starting cyclohexanones.
K. Maeda, R. Matsubara, M. Hayashi, Org. Lett., 2021, 23, 1530-1534.
A highly efficient Ni(II)-catalyzed photoredox N-arylation of Cbz-amines/Boc-amines with aryl electrophiles at room temperature provides a wide variety of N-aromatic and N-heteroaromatic carbamate products that find use in the synthesis of several biologically active molecules. The reaction offers a viable alternative to traditional palladium-catalyzed Buchwald-Hartwig reaction.
L. R. Reddy, S. Kotturi, Y. Waman, V. R. Reddy, C. Patel, A. Kobarne, S. Kuttappan, J. Org. Chem., 2018, 83, 13854-13860.
A Synthetic Approach to N-Aryl Carbamates via Copper-Catalyzed Chan-Lam Coupling at Room Temperature
S.-Y. Moon, U. Bin Kim, D.-B. Sung, W.-S. Kim, J. Org. Chem., 2015, 80, 1856-1865.
A photoinduced transition-metal-free C(aryl)-N bond formation between 2,4,6-tri(aryl)boroxines or arylboronic acids and 1,4,2-dioxazol-5-ones (dioxazolones) provides N-arylamides under mild conditions. Chloride anions, either generated in situ by photodissociation of the chlorinated solvent or added separately as an additive, were found to play a critical cooperative role.
Z. Zhou, J. Kweon, H. Jung, D. Kim, S. Seo, S. Chang, J. Am. Chem. Soc., 2022, 144, 9161-9174.
A convenient, general, and high yielding Pd-catalyzed cross-coupling of methanesulfonamide with aryl bromides and chlorides eliminates concern over genotoxic impurities that can arise when an aniline is reacted with methanesulfonyl chloride. The application of this method to the synthesis of dofetilide is also reported.
B. R. Rosen, J. C. Ruble, T. J. Beauchamp, A. Navarro, Org. Lett., 2011, 13, 2564-2567.
Iridium-catalyzed direct ortho C-H amidation of arenes works well with sulfonyl- and aryl azides as the nitrogen source. The reaction proceeds efficiently with a broad range of conventional directing groups with excellent functional group compatibility under mild conditions via 5- as well as 6-membered iridacycle intermediates.
D. Lee, Y. Kim, S. Chan, J. Org. Chem., 2013, 78, 11102-11109.
Direct Synthesis of Paracetamol via Site-Selective Electrochemical Ritter-type C-H Amination of Phenol
I. M. Taily, D. Saha, P. Banerjee, Org. Lett., 2022, 24, 2310-2314.
1,1,1-Trimethylhydrazinium Iodide: A Novel, Highly Reactive Reagent for Aromatic Amination via Vicarious Nucleophilic Substitution of Hydrogen
P. F. Pagoria, A. R. Mitchell, R. D. Schmidt, J. Org. Chem., 1996, 61, 2934-2935.