PHOSPHORUS, SULFUR, AND SILICON
7
only at the beginning of the reaction under non-nucleophilic Synthesis of N-chloro-N-(4-methylphenyl)acetamide
neutral conditions and then it would be accompanied by the
N-Chloro-N-(4-methylphenyl)acetamide was prepared as
colorless crystals in 70% yield by following the reported
procedure.34 1H NMR (400 MHz, CDCl3): δ = 2.05 (s, 3H,
CH3), 2.40 (s, 3H, CH3), 7.23−7.28 (m, 4H, ArH).
acid-catalyzed ionic rearrangement. The current results do not
provide any evidence for the concerted Cl[1,3] sigmatropic shift
mechanism.
Attempts to trap the chlorine radical with TEMPO were
performed, but failed, possibly due to the existence of the
hydrochloric acid generated in the reaction system.
Thermal rearrangement of
N-chloro-N-(4-methylphenyl)acetamide in anisole
Conclusion
N-Chloro-N-(4-methylphenyl)acetamide (366 mg, 2 mmol) was
The thermal 1,3-chlorine migration reactions of N-chloro-N-(4- dissolved in anisole (5 mL) in a round-bottom flask under
methylphenyl)acetamide under nucleophilic neutral conditions nitrogen. After covered the flask with aluminum foil, the solu-
in anisole as the solvent and under non-nucleophilic neutral tion was heated at 110°C under stirring for 12 h. The reaction
conditions in cumene as the solvent have been investigated. The mixture was monitored by TLC and GC-MS. Evaporation of the
results indicate that the thermal 1,3-chlorine migration occurs solvent and purification by silica gel column chromatography
through an ionic process under nucleophilic neutral conditions. afforded products N-(4-methylphenyl)acetamide 259 mg (87%
However, under non-nucleophilic neutral conditions, it is ini- yield), 4-chloroanisole 234 mg (82%). In addition, GC analysis
tiated by the radical homolysis of the Cl-N bond and subse- of the crude reaction mixture indicated that both N-(2-chloro-
quent radical combination of the Cl-C bond on the aromatic 4-methylphenyl)acetamide and 2-chloroanisole generated in 9%
rings. After generation of hydrochloric acid in the radical sub- yield.
stitution, the migrations occurred through the acid-catalyzed
rearrangement, similar to the acid-catalyzed Orton reaction.
The current results provide a comprehensive understanding on
the mechanistic insights in the Orton reaction under different
conditions.
Thermal rearrangement of
N-chloro-N-(4-methylphenyl)acetamide in cumene
N-Chloro-N-(4-methylphenyl)acetamide (366 mg, 2 mmol)
was dissolved in cumene (5 mL) in a round-bottom flask.
After covered the flask with aluminum foil, the solution
was heated at 110°C under stirring for 12 h. The reaction
mixture was monitored by TLC and GC-MS. Evaporation
of the solvent and purification by silica gel column chro-
matography afforded products N-(4-methylphenyl)acetamide
256 mg (86% yield), 4-chlorocumene 215 mg (70% yield) and
(1-chloromethyl)vinylbenzene 61 mg (20% yield). In addi-
tion, GC analysis of the crude reaction mixture indicated
that N-(2-chloro-4-methylphenyl)acetamide, 4-chlorocumene,
and 2-chlorocumene generated in 5%, 4.5%, and 0.5% yields,
respectively.
Experimental
Cumene was dried over CaCl2 and refluxed with sodium wire
and benzophenoneas an indicator under nitrogen, and freshly
distilled prior to use. Anisole was dried over CaCl2 and refluxed
1
over CaH2 under nitrogen and freshly distilled prior to use. H
and 13C NMR spectra were recorded on a 400 MHz spectrome-
ter in CDCl3 with TMS as an internal standard and the chemical
shifts (δ) are reported in parts per million (ppm). Melting points
were obtained on a melting point apparatus and are uncorrected.
GC-MS measurements were carried out on GC System with a
Mass Selective Detector. TLC analysis was performed on silica
gel GF254 plates. Spots were visualized with UV light or iodine.
Column chromatography was performed on silica gel (200–300
Funding
mesh) with a mixture of petroleum ether (PE) (60–90°C) and This work was supported in part by the National Basic Research Program
of China (No. 2013CB328905), the National Natural Science Foundation of
ethyl acetate (EA) as an eluent.
China (Nos. 21372025 and 21572017).
Synthesis of N-(4-methylphenyl)acetamide
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1
(
(
CH2Cl2) (Lit.35 154°C). H NMR (400 MHz, CDCl3): δ = 2.13
s, 3H, CH3), 2.30 (s, 3H, CH3), 7.09 (d, J = 8.2 Hz, 2H, ArH),
1
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7
.37 (d, J = 8.3 Hz, 2H, ArH), 7.60 (br, 1H, NH).
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