582 JOURNAL OF CHEMICAL RESEARCH 2018
4-Methyl-5-formylthiazole (1): Light yellow solid; m.p. 74.0–75.1 °C
(lit.34 74.0–75.0 °C); 1H NMR (400 MHz, CDCl3): δ 10.13 (s, 1H), 8.97
(s, 1H), 2.81 (s, 3H). MS (ESI) m/z 128.0 [M + H]+.
yield. So we think the role of DMSO is probably to accelerate
the decomposition of aryldiazene radical 9 into aryl radical 11
under the mild conditions, although the hydrogen transfer from
THF is the rate-limiting step of the reaction.28
1
Ethylbenzene (3c): Colourless oil; H NMR (400 MHz, CDCl3): δ
7.33–7.27 (m, 2H), 7.24–7.17 (m, 3H), 2.68 (q, J = 7.6 Hz, 2H), 1.28 (t,
J = 7.6 Hz, 3H). The spectrum matched that previously reported.35
Ethoxybenzene (3d): Colourless oil; 1H NMR (400 MHz, CDCl3): δ
7.34–7.24 (m, 2H), 6.99–6.88 (m, 3H), 4.05 (q, J = 7.2 Hz, 2H), 1.44 (t,
J = 7.2 Hz, 3H). The spectrum matched that previously reported.36
Conclusions
In conclusion, we have developed a new and practical DMSO-
accelerated deamination of aromatic amines with t-BuONO
in THF for the reductive deamination of aromatic amines.
Mechanistic studies revealed that the role of DMSO is probably
to accelerate the decomposition of the aryldiazene radical to
the aryl radical under the mild reaction conditions. A wide
variety of aromatic amines with electron-withdrawing or
donating groups provided the corresponding products in good
yields under this system. The advantages of this process are
operational convenience, environmentally friendly procedure,
mild reaction conditions, short reaction times and high yields.
1
Bromobenzene (3e): Colourless oil; H NMR (400 MHz, CDCl3):
δ 7.53–7.49 (m, 2H), 7.34–7.27 (m, 1H), 7.27–7.22 (m, 2H). The
spectrum matched that previously reported.37
1,4-Dichlorobenzene (3f): White solid; m.p. 52.2–52.9 °C (lit.38
52.8–53.0 °C); 1H NMR (400 MHz, CDCl3): δ 7.27 (s, 4H).
Benoic acid (3g): White solid; m.p. 122.2–122.9 °C (lit.39
1
122.0–122.5 °C); H NMR (400 MHz, CDCl3): δ 8.17–8.09 (m, 2H),
7.67–7.57 (m, 1H), 7.52–7.45 (m, 2H).
Methyl benzoate (3h): Colourless oil; 1H NMR (400 MHz, CDCl3): δ
8.07–8.01 (m, 2H), 7.60–7.52 (m, 1H), 7.48–7.40 (m, 2H), 3.93 (s, 3H).
The spectrum matched that previously reported.40
Experimental
Diphenylmethanone (3i): White solid; m.p. 47.5–48.3 °C (lit.41
48.1 °C); 1H NMR (400 MHz, CDCl3): δ 7.84–7.78 (m, 2H), 7.63–7.56
(m, 1H), 7.53–7.45 (m, 2H).
All reagents were obtained from commercial suppliers and used
without further purification, unless otherwise indicated. TLC
analysis was performed using pre-coated glass plates. Silica gel for
column chromatography was purchased from the Qingdao Haiyang
Chemical Co. Ltd. Melting points were determined using a Büchi
B-540 capillary melting point apparatus and are uncorrected. GC
analysis was determined by an Agilent Technologies 6890N Network
GC System and Agilent Technologies 7683B Series Injector. 1H NMR
and 13C NMR were recorded on a Varian Mercury Plus 400 instrument
at 400 and 100 MHz, respectively, and TMS was used as internal
standard. Mass spectra were measured with a Thermo Finnigan LCQ-
Advantage instrument. High resolution mass spectroscopic (HRMS)
analysis was performed on a Bruker microTOF-Q II instrument using
ESI techniques.
1
Nitrobenzene (3j): Light yellow oil; H NMR (400 MHz, CDCl3):
δ 8.25–8.21 (m, 2H), 7.73–7.67 (m, 1H), 7.58–7.52 (m, 2H). The
spectrum matched that previously reported.42
1-Methoxy-3-nitrobenzene (3m): Yellow solid; m.p. 37.6–38.3 °C
(lit.43 37.5–38.5 °C);1H NMR (400 MHz, CDCl3): δ 7.84–7.81 (m, 1H),
7.74–7.72 (m, 1H), 7.46–7.40 (m, 1H), 7.25–7.20 (m, 1H), 3.90 (s, 3H).
1-Chloro-3-nitrobenzene (3n): Light yellow solid; m.p. 45.8–46.7 °C
(lit.44 45.3–45.8 °C); 1H NMR (400 MHz, CDCl3): δ 8.23 (t, J = 2.4 Hz,
1H), 8.16–8.11 (m, 1H), 7.72–7.64 (m, 1H), 7.51 (t, J = 8.0 Hz, 1H).
1,3-Dinitrobenzene (3o): Yellow solid; m.p. 89.3–90.5 °C (lit.45
89–90 °C);1H NMR (400 MHz, CDCl3): δ 9.08 (t, J = 2.0Hz, 1H), 8.58
(dd, J = 8.0, 2.0 Hz, 2H), 7.82 (t, J = 8.0 Hz, 1H).
Reductive deamination of aromatic amines (2); general procedure
1,3-Dichloro-5-nitrobenzene (3q): Light yellow solid; m.p.
63.5–64.5 °C (lit.43 63.8–64.2 °C); 1H NMR (400 MHz, CDCl3): δ 8.13
(d, J = 1.6 Hz, 2H), 7.70 (t, J = 1.6 Hz, 1H).
A solution of amine 2 (5 mmol) in THF (3 mL) was added dropwise
over 20 min to a solution of t-BuONO (7.5 mmol) and DMSO
(0.5 mmol) in THF (7 mL) at 30 °C. The mixture was stirred at 30 °C
until the starting materials 2 were consumed (monitored by TLC). The
solvent was evaporated, and the yields of the low boiling point products
were determined by GC; the high boiling point products were isolated
by column chromatography on silica gel (hexane/ethyl acetate).
Methyl 3,5-dibromobenzoate (3r): White solid; m.p. 62.3–63.1 °C
1
(lit.46 62–63 °C); H NMR (400 MHz, CDCl3): δ 8.10 (d, J = 1.6 Hz,
2H), 7.84 (t, J = 1.6 Hz, 1H), 3.94 (s, 1H).
3,5-Dichlorobenzoic acid (3s): White solid; m.p. 187.3–188.5 °C
(lit.47 186–188 °C); 1H NMR (400 MHz, CDCl3): δ 7.98 (d, J = 2.0 Hz,
2H), 7.61 (t, J = 2.0 Hz, 1H), 1.27 (s, 1H).
Deuterodeamination reaction (3a’); general procedure
Benzothiazole (3u): Light yellow oil; 1H NMR (400 MHz, CDCl3): δ
8.99 (s, 1H), 8.15 (d, J = 8.4 Hz, 1H), 7.96 (d, J = 8.0 Hz, 1H), 7.56–7.49
(m, 1H), 7.44 (t, J = 7.2 Hz, 1H). The spectrum matched that previously
reported.48
The amine 2a (0.172 g, 1 mmol) and DMSO (8 mg, 0.1 mmol) were
added to an oven dried Schlenck tube. The system was evacuated
and filled with argon (three times) before dry d8-THF (0.5 mL) was
added, and the reaction mixture was stirred vigorously for 5 min.
Then t-BuONO (0.154 g, 1.5 mmol) was added and the stirring was
continued at 30 °C for 1 h. The solvent was evaporated off and the
crude product was purified by column chromatography on silica
gel (hexane/ethyl acetate = 8:1) to obtain the deuterated product 3a’
(0.147 g, 93% yield).
Pyridine (3v): Colourless liquid; 1H NMR (400 MHz, CDCl3): δ 8.60
(d, J = 4.8 Hz, 2H), 7.65 (t, J = 7.6 Hz, 1H), 7.30–7.24 (m, 2H). The
spectrum matched that previously reported.49
5-Bromo-2-chloropyrimidine (3w): White soild; m.p. 78.5–79.9 °C
(lit.50 78–79 °C);1H NMR (400 MHz, CDCl3): δ 8.68 (s, 2H).
2-Phenethoxytetrahydrofuran (5): Colourless oil; 1H NMR (400
MHz, CDCl3): δ 7.33–7.16 (m, 5H), 5.13 (dd, J = 4.0, 2.4 Hz, 1H),
3.95–3.79 (m, 3H), 3.66–3.57 (m, 1H), 2.89 (t, J = 7.2 Hz, 2H),
2.07–1.77 (m, 4H); 13C NMR (100 MHz, CDCl3): δ 139.1, 128.9 (2C),
128.2 (2C), 126.0, 103.9, 68.0, 67.0, 36.6, 32.6, 23.7; HRMS (ESI) m/z
calcd for C12H16NaO2 [M + Na]+: 215.1043; found: 215.1050.
Methyl 2-deuterio-4-methylthiazole-5-carboxylate (3a’): White
Synthesis of methyl 4-methyl-2-[(2,2,6,6-tetramethylpiperidinyl)1-
oxy]thiazole- 5-carboxylate (7); general procedure
A solution of amine 2a (0.866 g, 5 mmol) in THF (3 mL) was added
dropwise over 20 min to a solution of t-BuONO (0.772 g, 7.5 mmol)
and DMSO (39 mg, 0.5 mmol) in THF (7 mL) at 30 °C. Subsequently,
2,2,6,6-tetramethylpiperidinyl-1-oxy radical (TEMPO) (780 mg,
5 mmol) was added and the reaction mixture was stirred vigorously at
30 °C for 1.5 h. The solvent was evaporated off and the crude product
was purified by column chromatography on silica gel (hexane/ethyl
acetate = 15:1) to obtain the aryl radical/TEMPO adduct 7 (0.547 g,
35% yield).
1
solid; m.p. 74.2–75.3 °C (lit.24 74.0–76.0 °C); H NMR (400 MHz,
CDCl3): δ 8.81 (s, 0.07H), 3.92 (s, 3H), 2.81 (s, 3H).
4-Methyl-2-[(2,2,6,6-tetramethylpiperidinyl)1-oxy]thiazole-5-
carboxylate (7): Colourless oil; 1H NMR (400 MHz, CDCl3): δ 3.80 (s,
3H), 2.56 (s, 3H), 1.68–1.56 (m, 5H), 1.45–1.39 (m, 1H), 1.26 (s, 6H),
1.20 (s, 6H). 13C NMR (100 MHz, CDCl3): δ 182.7, 163.1, 157.6, 113.6,
62.4 (2C), 51.6, 39.5 (2C), 32.4 (2C), 20.9 (2C), 17.7, 16.6. HRMS (ESI)
m/z calcd for C15H24N2NaO3S [M + Na]+: 335.1424; found: 335.1410.
Methyl 4-methylthiazole-5-carboxylate (3a): White solid; m.p.
74.2–75.3 °C (lit.24 74.0–76.0 °C); 1H NMR (400 MHz, CDCl3): δ 8.77
(s, 1H), 3.89 (s, 3H), 2.79 (s, 3H). MS (ESI) m/z 158.1 [M + H]+.