596 J . Org. Chem., Vol. 67, No. 2, 2002
Notes
Commercially obtained materials were used as received
without further purification. Aryl halides, ligands, reagents, and
solvents were purchased from Fluka Chemical Co. with the
exception 3-bromobenzotrifluoride (Novartis AG). Anhydrous
dioxane (stored over molecular sieves) was used. PdCl2(PPh3)2
was purchased from Avocado Chemical Co.
Sch em e 1
1H and 13C{1H} NMR spectra were recorded on a Bruker dpx
300 spectrometer. Chemical shifts (δ) are given in ppm and refer
to TMS as internal standard. IR spectra were recorded on a
Perkin-Elmer 1710 spectrometer. Melting points were measured
with a Bu¨chi 520 apparatus and are uncorrected. The combus-
tion analyses were carried out by Solvias AG, Switzerland.
N-F or m yl-m -tr iflu or om eth ylben zim id e (Ta ble 2, en tr y
1). The autoclave was charged with 3-bromobenzotrifluoride
(8.01 g, 35.6 mmol), triethylamine (3.85 g, 38.0 mmol), forma-
mide (3.20 g, 71.2 mmol), PdCl2(PPh3)2 (243 mg, 0.35 mmol, 1
mol %), and 1,4-dioxane (25 mL). The autoclave was purged
three times with nitrogen (6 bar) and charged with 5 bar CO,
and the reaction mixture was heated to 120 °C. After 8 h and
cooling to room temperature, acetic acid (5 mL) was added to
the reaction mixture, and it was partitioned between dichlo-
romethane and water. The aqueous layer was extracted two
times with additional dichloromethane. The organic phases were
combined, dried (Na2SO4), and concentrated under reduced
pressure. The crude material was purified by column chroma-
tography (silica gel, EtOAc/hexane 1:2 as eluent). The title
compound (5.1 g, 23.5 mmol, 66%) was obtained as colorless
crystals. Rf ) 0.42 (EtOAc:hexane 1:2); mp: 130.0-130.5 °C; 1H
NMR (300.1 MHz, DMSO-d6, 297 K) δ 11.96 (d, J ) 8.6 Hz, 1H),
9.28 (d, J ) 8.4 Hz, 1H), 8.34 (s, 1H), 8.30 (d, J ) 7.9 Hz, 1H),
8.03 (dd, J ) 7.8 Hz, 0.7 Hz, 1H), 7.79 (t, J ) 7.8 Hz, 1H); 13C-
{1H} NMR (75.5 MHz, DMSO-d6, 297 K) δ 167.2, 165.2, 133.6,
133.3, 130.8, 130.6 (q, J (C-F) ) 4 Hz), 130.3 (q, J (C-F) ) 32
Hz), 125.9 (q, J (C-F) ) 4 Hz), 124.6 (q, J (C-F) ) 272 Hz); IR
(KBr, cm-1) 3246, 1740, 1678, 1469; Anal. Calcd for C9H6F3-
NO2: C, 49.78; H, 2.79; N, 6.45; F, 26.25; O, 14.74. Found: C,
49.89; H, 2.83; N, 6.27; F, 26.08; O, 14.75.
Sch em e 2
The imides were easily hydrolyzed under aqueous basic
conditions which was already noticed for formimides by
Ueda et al.6a Therefore, the excess base had to be
neutralized prior to the workup, or alternatively, the
workup had to be carried out under anhydrous condi-
tions.
The course of the hydrolysis depends mainly on the R
group of the amide and their influence on the electro-
philicity of the carbonyl group (see Table 2). With
formimides the more electrophilic formyl group was
attacked by a nucleophile, and the primary benzoyl amide
and formic acid were formed (Scheme 2), whereas acetyl-
benzimides were decomposed to the benzoic acids and
acetamides.
The method described here is an interesting alternative
to our previous protocol for the synthesis of primary
benzamides using DMAP, especially since the yields of
the primary amide was higher with NEt3 followed by a
basic workup than in the direct reaction with DMAP
(Table 1, entries 2 and 3). Moreover, the reaction times
were shorter, and it was easier to determine the end of
the reaction.
Our protocol expands the scope of the aminocarbony-
lation of aryl halides to the synthesis of aroyl imides.
Despite their low nucleophilicity, a broad range of
primary amides and sulfonamides react readily to the
corresponding imides. The reaction conditions are rea-
sonably mild, and all starting materials are stable and
easy to handle; therefore, the protocol is well suited for
laboratory synthesis and has the potential for large scale
production.
In addition, 1.45 g (7.7 mmol, 22%) of 3-trifluoromethylbenz-
amide was obtained as yellow crystals. Rf ) 0.06 (EtOAc:hexane
1:2);1H NMR (300.1 MHz, DMSO-d6, 297 K) δ 8.25 (s (br), 1H),
8.22-8.17 (m, 2H), 7.89 (dd, J ) 7.8 Hz, 0.7 Hz, 1H), 7.71 (t, J
) 7.8 Hz, 1H), 7.64 (s (br), 1H).
N-F or m yl-p-m eth oxyben zim id e (Ta ble 2, en tr y 3). The
reaction of 4-bromoanisole (6.86 g, 35.6 mmol) with formamide
(3.21 g, 71.2 mmol) was effected using the procedure described
above, but with additional triphenylphosphine (377 mg, 1.4
mmol). After a reaction time of 12 h, 10 M hydrochloric acid (0.5
mL) and methanol (170 mL) were added, the mixture was cooled
to -78 °C, and the precipitate was filtered to afford 3.70 g (20.6
mmol, 58%) of the title compound as a colorless solid. mp: 203-
205 °C; 1H NMR (300.1 MHz, DMSO-d6, 297 K) δ 11.42 (d, J )
9.0 Hz, 1H), 9.04 (d, J ) 9.0 Hz, 1H), 7.83 (d, J ) 8.8 Hz, 2H),
6.87 (d, J ) 8.8 Hz, 2H), 3.65 (s, 3H); 13C{1H} NMR (75.5 MHz,
DMSO-d6, 297 K) δ 167.5, 165.4, 164.3, 131.5 (2C), 124.3, 114.8
(2C), 56.4; IR (KBr, cm-1) 3261, 1725, 1675, 1465, 1375. Anal.
Calcd for C9H9NO3: C, 60.33; H, 5.06; N, 7.82; O, 26.79. Found:
C, 60.09; H, 5.07; N, 7.83; O, 26.79.
N-Acetyl-m -tolu im id e (Ta ble 2, en tr y 5). The reaction of
3-bromotoluene (6.15 g, 35.6 mmol) with acetamide (4.25 g, 71.2
mmol) was effected using the procedure described above, but
with additional triphenylphosphine (377 mg, 1.4 mmol). After a
reaction time of 20 h, acetic acid (5 mL) and dichloromethane
(250 mL) were added to afford a orange solution. Diethyl ether
(300 mL) was added, and the precipitate was filtered off. The
filtrate was concentrated under reduced pressure, and the
residue was purified by column chromatography (silica gel,
EtOAc/hexane as eluent). Yellow crystals (4.97 g) were obtained
containing ca. 90% (28.0 mmol, 67%) of the title compound. Rf
) 0.32 (EtOAc:hexane 1:2); 1H NMR (300.1 MHz, DMSO-d6, 297
K) δ 10.73 (s (br), 1H), 7.53-7.48 (m, 2H), 7.24-7.15 (m, 2H),
2.16 (s 3H), 2.12 (s, 3H); 13C{1H} NMR (75.5 MHz, DMSO-d6,
297 K) δ 172.9, 167.4, 138.7, 134.1, 134.0, 129.7, 129.2, 126.4,
26.4, 21.7; IR (KBr, cm-1) 3304, 1713, 1682, 1672, 1458. Anal.
Calcd for C10H11NO3: C, 67.78; H, 6.26; N, 7.90; O, 18.06. Found
(after crystallization from hexane): C, 67.48; H, 6.24; N, 7.90;
O, 17.95.
Exp er im en ta l Section
Gen er a l Con sid er a tion s. For the carbonylation experi-
ments, a 250 mL glass autoclave equipped with a magnet-driven
hollow shaft stirrer was used. The reactions were carried out
under nonisobaric conditions, and the progress of reaction was
followed by measuring the pressure in the autoclave. CO gas
(purity 99.97%) was purchased from Carbagas Chemical Co.