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Synlett 2014; 25(11): 1550-1554
DOI: 10.1055/s-0033-1339107
letter
© Georg Thieme Verlag Stuttgart · New York

Copper-Catalyzed N-tert-Butylation of Aromatic Amines under Mild Condi­tions Using tert-Butyl 2,2,2-Trichloroacetimidate

John W. Cran*
Department of Chemistry and Biochemistry, Florida State University, Tallahassee, FL 32306-4390, USA   Fax: +1(850)6447409   Email: jcran@chem.fsu.edu
,
Dinesh V. Vidhani
Department of Chemistry and Biochemistry, Florida State University, Tallahassee, FL 32306-4390, USA   Fax: +1(850)6447409   Email: jcran@chem.fsu.edu
,
Marie E. Krafft
Department of Chemistry and Biochemistry, Florida State University, Tallahassee, FL 32306-4390, USA   Fax: +1(850)6447409   Email: jcran@chem.fsu.edu
› Author Affiliations
Further Information

Publication History

Received: 10 March 2014

Accepted after revision: 10 April 2014

Publication Date:
23 May 2014 (online)

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Abstract

A variety of aromatic amines have been found to expediently undergo copper-catalyzed N-tert-butylation in the presence of tert-butyl 2,2,2-trichloroactimidate at room temperature.

Key words

anilines - tert-butylation - copper - catalysis - alkylation
 

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  • 12 General Experimental Methods All commercially available chemicals were used as received. MeNO2 and CH2Cl2 were distilled from CaH2. Reagent-grade solvents were used for solvent extraction, and organic extracts were dried over anhydrous Na2SO4 or MgSO4. Alumina gel (80–200 mesh) was used for flash chromatography with dry hexane–EtOAc eluent system.1H NMR spectra were recorded on a 500 MHz Bruker or a 300 MHz Varian spectrometer. 13C NMR spectra were recorded on a 125 MHz Bruker or a 75 MHz Varian spectrometer. The proton chemical shifts (δ) are reported as parts per million relative to 7.26 ppm for CDCl3. The carbon chemical shifts (δ) were reported as parts per million relative to the centerline of the triplet for CDCl3 at 77.1 ppm. Mass spectra were recorded using a Jeol JMS-600 instrument or an Agilent 6220 TOF-MS (NSF CRIF Grant 0541761). Typical Procedure for tert-Butylation Reaction To a dry round-bottom flask, equipped with a stirrer bar, under argon was added freshly distilled MeNO2 (2.5 mL), tert-butyl 2,2,2-trichloroacetimidate (0.45 mL, 2.5 mmol), amine (1.0 mmol), and CuOTf (18 mg, 0.05 mmol). The reaction was stirred at r.t. for 2 h, or until the reaction was observed to have gone to completion by TLC or 1H NMR spectroscopy of small aliquots of the reaction mixture. The reaction mixture was then diluted with EtOAc (25 mL) and washed with aq sat. NaHCO3 solution (20 mL). The aqueous phase was extracted with an additional portion of EtOAc (20 mL). The combined organic extracts were dried with Na2SO4 and filtered through a plug of alumina before being reduced in vacuo. The crude product was purified by flash column chromatography (typically 20:1, hexane–EtOAc).
  • 13 tert-Butylphenylamine (2) Clear oil (125 mg, 0.84 mmol, 84% yield). 1H NMR (300 MHz, CDCl3): δ = 7.16 (dd, J = 8.1, 8.1 Hz, 2 H), 6.79–6.73 (m, 3 H), 3.30–2.30 (br s, 1 H), 1.34 (s, 9 H). Compound identified by 1H NMR spectroscopy by comparison with data previously published in the literature.1a 4-tert-Butylaminobenzoic Acid Methyl Ester (3) Light yellow oil (208 mg, 1.00 mmol, 99% yield). 1H NMR (300 MHz, CDCl3): δ = 7.81 (d, J = 9.0 Hz, 2 H), 6.63 (d, J = 9.0 Hz, 2 H), 4.25–4.00 (br s, 1 H), 3.84 (s, 3 H), 1.40 (s, 9 H). 13C NMR (125 MHz, CDCl3): δ = 167.4, 151.0, 131.3 (2 C), 117,7, 113.7 (2 C), 51.3, 29.7 (3 C). ESI-HRMS: m/z calcd for C12H18NO2 [MH]+: 208.1338; found: 208.1349. 1-(4-tert-Butylaminophenyl)-ethanone (4) Yellow oil (189 mg, 0.99 mmol, 99% yield). 1H NMR (300 MHz, CDCl3): δ = 7.78 (d, J = 8.4 Hz, 2 H), 6.63 (d, J = 8.4 Hz, 2 H), 4.32 (br s, 1 H), 2.49 (s, 3 H), 1.41 (s, 9 H). 13C NMR (125 MHz, CDCl3): δ = 196.4, 151.2, 130.6 (2 C), 126.0, 113.5 (2 C), 51.3, 29.7 (3 C), 26.0. ESI-HRMS: m/z calcd for C12H18NO [MH]+: 192.1383; found: 192.1374. 4-tert-Butylaminobenzonitrile (5) Light brown oil (165 mg, 0.95 mmol, 95% yield). 1H NMR (300 MHz, CDCl3): δ = 7.37 (d, J = 9.0 Hz, 2 H), 6.62 (d, J = 9.0 Hz, 2 H), 4.30-4.10 (br s, 1 H), 1.40 (s, 9 H). Compound identified by 1H NMR spectroscopy by comparison with data previously published in the literature.14 tert-Butyl-(4-nitrophenyl)-amine (6) Yellow oil (192 mg, 0.99 mmol, 99% yield). 1H NMR (300 MHz, CDCl3): δ = 8.03 (d, J = 9.0 Hz, 2 H), 6.59 (d, J = 9.0 Hz, 2 H), 4.70–4.50 (br s, 1 H), 1.43 (s, 9 H). Compound identified by 1H NMR spectroscopy by comparison with data previously published in the literature.1a tert-Butyl-(2-nitro-4-trifluoromethyl-phenyl)-amine (7) Yellow oil (262 mg, 1.00 mmol, 99% yield). 1H NMR (300 MHz, CDCl3): δ = 8.68–8.56 (br s, 1 H), 8.45 (d, J = 2.4 Hz, 1 H), 7.56 (dd, J = 9.0, 2.4 Hz, 1 H), 7.18 (d, J = 15.0 Hz, 1 H), 1.53 (s, 9 H). 13C NMR (125 MHz, CDCl3): δ = 146.3, 133.4, 133.3 (q, J = 3.8 Hz), 125.5 (q, J = 43.8 Hz), 123.7, (q, J = 268.8 Hz), 116.7 (q, J = 30.0 Hz), 116.3, 52.3, 29.6 (3 C). ESI-HRMS: m/z calcd for C11H14N2O2F3 [MH]+: 263.1002; found: 263.1002. tert-Butyl-(4-trifluoromethyl-phenyl)-amine (8) Light brown oil (210 mg, 0.97 mmol, 97% yield). 1H NMR (300 MHz, CDCl3): δ = 7.37 (d, J = 9.0 Hz, 2 H), 6.69 (d, J = 9.0 Hz, 2 H), 3.97 (s, 1 H), 1.39 (s, 9 H). 13C NMR (75 MHz, CDCl3): δ = 149.7, 126.4 (q, J = 3.4 Hz, 2 C), 125.1 (q, J = 268.7 Hz), 118.5 (q, J = 32.4 Hz), 114.4 (2 C), 51.3, 29.8. ESI-HRMS: m/z calcd for C11H15NF3 [MH]+: 218.1151; found: 218.1153. tert-Butyl-(4-chloro-3-trifluoromethyl-phenyl)-amine (9) Light yellow oil (251 mg, 1.00 mmol, 99% yield). 1H NMR (300 MHz, CDCl3): δ = 7.22 (d, J = 9.0 Hz, 1 H), 6.97 (d, J = 3.0 Hz, 1 H), 6.77 (dd, J = 9.0, 3.0 Hz, 1 H), 4.02–3.02 (br s, 1 H), 1.35 (s, 9 H). 13C NMR (125 MHz, CDCl3): δ = 145.6, 131.8, 128.4 (q, J = 31.3 Hz), 123.1 (q, J = 271.3 Hz), 119.3, 119.2 (q, J = 1.3 Hz), 114.7 (q, J = 6.3 Hz), 51.6, 29.8 (3 C). HRMS (EI): m/z calcd for C11H13F3NCl [M]+: 251.0689; found: 251.0690. tert-Butyl-(4-chlorophenyl)-amine (10) Light orange oil (0.181 g, 0.99 mmol, 99% yield). 1H NMR (300 MHz, CDCl3): δ = 7.10 (d, J = 9.0 Hz, 2 H), 6.65 (d, J = 9.0 Hz, 2 H), 1.32 (s, 9 H). Compound identified by 1H NMR spectroscopy by comparison with data previously published in the literature.1a (2-Bromo-phenyl)-tert-butylamine (11) Pink oil (228 mg, 1.00 mmol, 99% yield). 1H NMR (300 MHz, CDCl3): δ = 7.43 (dd, J = 7.8, 1.8 Hz, 1 H), 7.14 (ddd, J = 7.8, 7.8, 1.8 Hz, 1 H), 6.97 (dd, J = 7.8, 1.8 Hz, 1 H), 6.55 (ddd, J = 7.8, 7.8, 1.8 Hz, 1 H), 4.40–4.25 (br s, 1 H), 1.41 (s, 9 H). Compound identified by 1H NMR spectroscopy by comparison with data previously published in the literature.4c (2-Bromo-6-methylphenyl)-tert-butylamine (12) Light pink oil (213 mg, 0.88 mmol, 88% yield). 1H NMR (300 MHz, CDCl3): δ = 7.39 (d, J = 7.8, 1 H), 7.11 (d, J = 7.8 Hz, 1 H), 6.82 (dd, J = 7.8, 7.8 Hz, 1 H), 3.37–3.29 (br s, 1 H), 2.42 (s, 3 H), 1.26 (s, 9 H). 13C NMR (125 MHz, CDCl3): δ = 143.9, 137.2, 130.5, 130.2, 124.3, 124.2, 56.1, 31.1 (3 C), 21.6. HRMS (EI): m/z calcd for C11H16BrN [M]+: 241.0466; found: 241.0476. tert-Butyl-o-tolylamine (13) Light brown oil (98 mg, 0.60 mmol, 60% yield). 1H NMR (300 MHz, CDCl3): δ = 7.13–7.04 (m, 2 H), 6.92 (d, J = 8.4 Hz, 1 H), 6.66 (dd, J = 7.2, 7.2 Hz, 1 H), 3.60–3.25 (br s, 1 H), 2.13 (s, 3 H), 1.40 (s, 9 H). Compound identified by 1H NMR spectroscopy by comparison with data previously published in the literature.1a tert-Butyl-m-tolylamine (14) Light brown oil (135 mg, 0.83 mmol, 83% yield). 1H NMR (300 MHz, CDCl3): δ = 7.06 (dd, J = 9.0, 9.0 Hz, 1 H), 6.62–6.55 (m, 3 H), 3.20–2.65 (br s, 1 H), 2.28 (s, 3 H), 1.34 (s, 9 H). Compound identified by 1H NMR spectroscopy by comparison with data previously published in the literature.1c tert-Butyl-p-tolylamine (15) Light brown oil (132 mg, 0.81 mmol, 81% yield). 1H NMR (300 MHz, CDCl3): δ = 6.99 (d, J = 8.4 Hz, 2 H), 6.71 (d, J = 8.4 Hz, 2 H), 3.30–2.40 (br s, 1 H), 2.26 (s, 3 H), 1.30 (s, 9 H). Compound identified by 1H NMR spectroscopy by comparison with data previously published in the literature.1a tert-Butyl-(4-methoxyphenyl)-amine (17) Red oil (127 mg, 0.72 mmol, 72% yield). 1H NMR (300 MHz, CDCl3): δ = 6.84–6.73 (m, 4 H), 3.76 (s, 3 H), 1.23 (s, 9 H). Compound identified by 1H NMR spectroscopy by comparison with data previously published in the literature.1a Biphenyl-4-yl-tert-butylamine (19) Light yellow oil (196 mg, 0.87 mmol, 87% yield). 1H NMR (300 MHz, CDCl3): δ = 7.55 (d, J = 7.2 Hz, 2 H), 793 (d, J = 8.4 Hz, 2 H), 7.40 (t, J = 7.5 Hz, 2 H), 7.26 (t, J = 7.5 Hz, 1 H), 6.82 (d, J = 9.0 Hz, 2 H), 4.00–3.20 (br s, 1 H), 1.39 (s, 9 H). Compound identified by 1H NMR spectroscopy by comparison with data previously published in the literature.15 tert-Butyl-(4-nitro-naphthalen-1-yl)-amine (20) Yellow oil (203 mg, 0.83 mmol, 83% yield). 1H NMR (300 MHz, CDCl3): δ = 9.05 (d, J = 9.0 Hz, 1 H), 8.46 (d, J = 9.0 Hz, 1 H), 7.76 (d, J = 9.0 Hz, 1 H), 7.67 (dd, J = 7.8, 7.8 Hz, 1 H), 7.51 (dd, J = 7.8, 7.8 Hz, 1 H), 6.78 (d, J = 9.0 Hz, 1 H), 5.38–5.31 (br s, 1 H), 1.58 (s, 9 H). 13C NMR (75 MHz, CDCl3): δ = 148.5, 134.1, 129.5, 129.1, 128.1, 125.7, 125.0, 122.5, 120.1, 103.5, 52.2, 29.4 (3 C). HRMS (EI): m/z calcd for C14H16O2N2 [M]+: 244.1212; found: 244.1212. tert-Butyl-naphthalen-2-yl-amine (22) Red oil (123 mg, 0.62 mmol, 62% yield). 1H NMR (300 MHz, CDCl3): δ = 7.66 (d, J = 8.4 Hz, 1 H), 7.61 (d, J = 8.4 Hz, 2 H), 7.36 (dd, J = 7.5, 7.5 Hz, 1 H), 7.20 (dd, J = 7.5, 7.5 Hz, 1 H), 7.04 (d, J = 2.4 Hz, 1 H), 6.90 (dd, J = 9.0, 2.4 Hz, 1 H), 4.00–3.20 (br s, 1 H), 1.43 (s, 9 H). Compound identified by 1H NMR spectroscopy by comparison with data previously published in the literature.16
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