Iron-Catalyzed Direct Transformation of Benzylic Amines into Carbonyl Compounds in Water

Abstract

Fe-catalyzed direct transformation of benzylic amines into carbonyl compounds was performed in H₂O. The reaction of benzylic amines with formaldehyde in the presence of FeCl₃·6H₂O in H₂O afforded the corresponding carbonyl compounds (80 °C to reflux conditions; 14 examples, up to 94% yield). O¹⁸-labeling experiments indicated that the O atom in the generated carbonyl is derived from H₂O.

Key words

direct transformation - benzylic amines - carbonyl compounds - iron catalysis - formaldehyde

• References and Notes

• 1a Nicolaou KC, Mathison CJ. N, Montagnon T. J. Am. Chem. Soc. 2004; 126: 5192
• 1b Chu G, Li C. Org. Biomol. Chem. 2010; 8: 4716
• 1c Galletti P, Funiciello F, Soldati R, Giacomini D. Adv. Synth. Catal. 2015; 357: 1840
• 1d Patil VV, Gayakwad EM, Shankarling GS. J. Org. Chem. 2016; 81: 781
• 1e Wang Y, Kaboyashi H, Yamaguchi K, Mizuno N. Chem. Commun. 2012; 48: 2642
• 1f Gaspa S, Porcheddu A, Valentoni A, Garroni S, Enzo S, De Luca L. Eur. J. Org. Chem. 2017; 5519
• 1g Iqbal N, Cho EJ. Adv. Synth. Catal. 2015; 357: 2187
• 1h Ratnikov MO, Farkas LE, McLaughlin EC, Chiou G, Choi H, El-Khalafy SH, Doyle MP. J. Org. Chem. 2011; 76: 2585
• 1i Hamamoto H, Suzuki Y, Takahashi H, Ikegami S. Tetrahedron Lett. 2007; 48: 4239
• 1j Golime G, Bogonda G, Kim H, Oh K. ACS Catal. 2018; 8: 4986
• 1k Telvekar VN, Chaudhari HK. Synth. Commun. 2013; 43: 1155
• 1l Hudwekar AD, Reddy GL, Verma PK, Gupta S, Vishwakarma RA, Sawant SD. ChemistrySelect 2017; 2: 4963
• 1m Srogl J, Voltrova S. Org. Lett. 2009; 11: 843
• 1n Knowles DA, Mathews CJ, Tomkinson NC. O. Synlett 2008; 2769
• 1o Miyazawa A, Tanaka K, Sakakura T, Tashiro M, Tashiro H, Prakash GK. S, Olah GA. Chem. Commun. 2005; 2104
• 2 Clayden J, Greeves N, Warren S, Wothers P. Organic Chemistry . Oxford University Press; Oxford: 2001
• 3a Minakawa M, Okubo M, Kawatsura M. Bull. Chem. Soc. Jpn. 2015; 88: 1680
• 3b Minakawa M, Okubo M, Kawatsura M. Tetrahedron Lett. 2016; 57: 4187
• 3c Minakawa M, Watanabe K, Toyoda S, Uozumi Y. Synlett 2018; 29: 2385
• 4a Issleib K, Döpfer K, Balszuweit A. Z. Naturforsch., B 1981; 36: 1392
• 4b Sugimoto H, Nakamura S, Ohwada T. Adv. Synth. Catal. 2007; 349: 669
• 4c Cele ZE. D, Pawar SA, Naicker T, Maguire GE. M, Arvidsson PI, Kruger HG, Govender T. Eur. J. Org. Chem. 2014; 2253
• 5 The reaction with an excess of amine to give an aminal seems to predominate over the conventional reaction (Scheme 1). On the other hand, the reaction with an excess of formaldehyde prevented the formation of an aminal in the presence of FeCl₃·6H₂O.
• 6 0.2 M aq HCl. The concentration was calculated for 1.0 mol equiv of HCl formed from FeCl₃·6H₂O (20 mol% based on amine).
• 7 0.6 M aq HCl. The concentration was calculated for 3.0 mol equiv of HCl formed from FeCl₃·6H₂O (20 mol% based on amine).
• 8 Benzophenone (3a); Typical Procedure (Table [2], Entry 1) A vial was charged with (diphenylmethyl)amine (1a; 91.6 mg, 0.5 mmol), FeCl₃·6H₂O (27.0 mg, 20 mol%), and paraformaldehyde (2; 19.2 mg, 0.6 mmol) under air. H₂O (0.5 mL) was added and the mixture was stirred at 100 °C for 18 h. The aqueous phase was then extracted with EtOAc (×3) and dried (Na₂SO₄). The extract was filtered through paper and concentrated in vacuo. The residue was purified by flash column chromatography [silica gel, EtOAc–hexane (1:10)] to give a white solid; yield: 85.2 mg (94%); mp 47.5–49.0 °C. ¹H NMR (500 MHz, CDCl₃): δ = 7.49 (t, J = 6.2 Hz, 4 H), 7.58–7.61 (m, 2 H), 7.81 (d, J = 6.2 Hz, 4 H). ¹³C NMR (125 MHz, CDCl₃): δ = 128.4, 130.2, 132.6, 137.7, 196.9.
• 9 When amines or imine intermediates were insoluble in water, 1,4-dioxane was added.
• 10 Although amines were consumed, the desired products were obtained in low yields.
• 11 Although the reactions of (pyridin-4-ylmethyl)amine, (pyrazin-2-ylmethyl)amine, and furfurylamine with formaldehyde were also performed under similar reaction conditions, the corresponding carbonyl compounds were not obtained. In addition, 4-nitrobenzylamine with formaldehyde gave 4-nitrobenzaldehyde in 7% yield under similar reaction conditions.
• 12 Without FeCl₃·6H₂O, N-(phenylmethylene)methanamine (6) was detected in quantitative yield after the reaction.
• 13 The yields were determined by ¹H NMR analysis of the crude mixtures (based on an internal standard). After the reaction, benzaldehyde (3f) was also detected in 35% yield.
• 14 The products ratio (O¹⁸/O¹⁶) was determined by GC–MS analysis.
• 15a Casey CP, Johnson JB. J. Am. Chem. Soc. 2005; 127: 1883
• 15b Brune HA, Unsin J, Hemmer R, Reichhardt M. J. Organomet. Chem. 1989; 369: 335
• 15c Gangadasu B, Narender P, China Raju B, Jayathira Rao V. Indian J. Chem., Sect. B: Org. Chem. Incl. Med. Chem. 2005; 44: 2598
• 15d Guthrie RD, Meister W, Cram DJ. J. Am. Chem. Soc. 1967; 89: 5288
• 15e Guthrie RD, Jaeger D, Meister W, Cram DJ. J. Am. Chem. Soc. 1971; 93: 5137
• 16a Pi D, Jiang K, Zhou H, Sui Y, Uozumi Y, Zou K. RSC Adv. 2014; 4: 57875
• 16b Jiang K, Pi D, Zhou H, Liu S, Zou K. Tetrahedron 2014; 70: 3056
• 16c Zhou Y, Shen G, Sui Y, Zhou H. Tetrahedron Lett. 2016; 57: 3396
• 16d Shen G, Zhou H, Sui Y, Liu Q, Zou K. Tetrahedron Lett. 2016; 57: 587
• 16e He R, Cui P, Pi D, Sun Y, Zhou H. Tetrahedron Lett. 2017; 58: 3571