Mo(CO)6-mediated carbamoylation of aryl halides

Article abstract of DOI:10.1021/jo101611g

A simple method for the synthesis of amides has been developed by molybdenum-mediated carbamoylation of aryl halides. Whereas the conventional palladium-catalyzed three-component coupling reaction requires a large excess of gaseous carbon monoxide, the incorporation of carbon monoxide in this Mo-mediated carbamoylation reaction is so efficient that it requires only a slight excess amount of carbon monoxide in the form of its molybdenum complex, Mo(CO)₆. The reaction is applicable for the synthesis of a wide variety of not only secondary and tertiary amides but also primary amides by using aqueous ammonia.

Full text of DOI:10.1021/jo101611g

pubs.acs.org/joc
Mo(CO)6-Mediated Carbamoylation of Aryl Halides
Wei Ren and Motoki Yamane*
Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences,
Nanyang Technological University, 21 Nanyang Link, Singapore 637371, Singapore
yamane@ntu.edu.sg
Received August 19, 2010
A simple method for the synthesis of amides has been developed by molybdenum-mediated
carbamoylation of aryl halides. Whereas the conventional palladium-catalyzed three-component coupling
reaction requires a large excess of gaseous carbon monoxide, the incorporation of carbon monoxide
in this Mo-mediated carbamoylation reaction is so efficient that it requires only a slight excess
amount of carbon monoxide in the form of its molybdenum complex, Mo(CO)6. The reaction is
applicable for the synthesis of a wide variety of not only secondary and tertiary amides but also primary
amides by using aqueous ammonia.
Introduction
metal carbonyl complexes such as Mo(CO)6 could be used as
the sources of carbon monoxide in the reaction under microwave
irradiation.2 Nevertheless, it still requires a large excess of metal
carbonyl complexes calculated on the basis of the stoichiom-
etric amount of carbon monoxide.3,4 In 1969, Corey and
Hegedus reported the synthesis of amides in the reaction
between aryl halides, Ni(CO)4, and amines.3h Although it
required 6 molar amounts of Ni(CO)4, it is noteworthy that
nickel carbonyl complex can also serve as a mediator to form
carbon-carbon and carbon-nitrogen bonds, apart from
being the source of carbon monoxide. Recently, our group
reported the carbamoylation of aryl halides by using group
VI metal amine carbonyl complexes (Scheme 1).5 The results
indicated that group VI metal carbonyl complexes as expected
It is well known that the palladium-catalyzed three-
component coupling reaction between aryl halides, carbon
monoxide, and amines is a very powerful synthetic method to
prepare amides.1 Various secondary and tertiary amides are
prepared from aryl halides with one-carbon elongation by
this method. However, it is necessary to use a large excess
amount of carbon monoxide because the reaction takes place
under gaseous carbon monoxide and sometimes high pres-
sure is required. Recently, it was reported that group VI
(1) For selected reviews, see: (a) Schoenberg, A.; Bartoletti, I.; Heck, R. F.
J. Org. Chem. 1974, 39, 3318. (b) Schoenberg, A.; Heck, R. F. J. Org. Chem. 1974,
39, 3327. (c) Schoenberg, A.; Heck, R. F. J. Am. Chem. Soc. 1974, 96, 7761.
(d) Barnard, C. F. J. Organometallics 2008, 27, 5402. (e) Yasui, Y.; Takemoto, Y.
Chem. Rec. 2008, 8, 386. (f) Beccalli, E. M.; Broggini, G.; Martinelli, M.;
Sottocornola, S. Chem. Rev. 2007, 107, 5318.
(2) (a) Wannberg, J.; Larhed, M. J. Org. Chem. 2003, 68, 5750. (b) Georgsson,
J.; Hallberg, A.; Larhed, M. J. Comb. Chem. 2003, 5, 350. (c) Wu, X.;
Mahalingam, A. K.; Wan, Y. Q.; Alterman, M. Tetrahedron Lett. 2004, 45,
4635. (d) Herrero, M. A.; Wannberg, J.; Larhed, M. Synlett 2004, 2335.
(3) For using aldehyde as the substitute for CO gas, see: (a) Morimoto, T.;
Fujioka, M.; Fuji, K.; Tsutsumi, K.; Kakiuchi, K. Chem. Lett. 2003, 32, 154.
(b) Morimoto, T.; Fujioka, M.; Fuji, K.; Tsutsumi, K.; Kakiuchi, K.
J. Organomet. Chem. 2007, 692, 625. For using formamide, see: (c) Wan,
Y. Q.; Alterman, M.; Larhed, M.; Hallberg, A. J. Comb. Chem. 2003, 5, 82.
For using dimethylformamide, see: (d) Hosoi, K.; Nozaki, K.; Hiyama, T.
Org. Lett. 2002, 4, 2849. (e) Wan, Y. Q.; Alterman, M.; Larhed, M.; Hallberg,
A. J. Org. Chem. 2002, 67, 6232. (f) Ju, J.; Jeong, M.; Moon, J.; Jung, H. M.;
Lee, S. Org. Lett. 2007, 9, 4615. (g) Tambade, P. J.; Patil, Y. P.; Bhanushali,
M. J.; Bhanage, B. M. Tetrahedron Lett. 2008, 49, 2221. For using Ni(CO)4,
see: (h) Corey, E. J.; Hegedus, L. S. J. Am. Chem. Soc. 1969, 91, 1233. For
using group VI metal carbonyl complexes, see ref 2.
€
(e) Yamazaki, K.; Kondo, Y. J. Comb. Chem. 2004, 6, 121. (f) Wu, X.; Ronn,
R.; Gossas, T.; Larhed, M. J. Org. Chem. 2005, 70, 3094. (g) Cao, H.; Xiao, W. J.
Can. J. Chem. 2005, 83, 826. (h) Wannberg, J.; Dallinger, D.; Kappe, C. O.;
Larhed, M. J. Comb. Chem. 2005, 7, 574. (i) Wannberg, J.; Kaiser, N.-F. K.;
Vrang, L.; Samuelsson, B.; Larhed, M.; Hallberg, A. J. Comb. Chem. 2005, 7, 611.
(j) Wu, X.; Larhed, M. Org. Lett. 2005, 7, 3327. (k) Lagerlund, O.; Larhed
M. J. Comb. Chem. 2006, 8, 4. (l) Wu, X.; Ekegren, J. K.; Larhed, M.
Organometallics 2006, 25, 1434. (m) Wu, X.; Wannberg, J.; Larhed, M. Tetra-
hedron 2006,62, 4665. (n) Gold, H.; Ax, A.; Vrang, L.; Samuelsson, B.; Karlen,A.;
Hallberg, A.; Larhed, M. Tetrahedron 2006, 62, 4671. (o) Letavic, M. A.; Ly, K. S.
Tetrahedron Lett. 2007, 48, 2339.
(4) Just after the submission of our manuscript, Roberts and co-workers
reported molybdenum-mediated carbonylation of aryl halides using micro-
wave irradiation. See: Roberts, B.; Liptrot, D.; Alcaraz, L.; Luker, T.;
Stocks, M. J. Org. Lett. 2010, 12, 4280.
ꢀ
(5) Ren, W.; Yamane, M. J. Org. Chem. 2010, 75, 3017.
8410 J. Org. Chem. 2010, 75, 8410–8415
Published on Web 11/18/2010
DOI: 10.1021/jo101611g
r
2010 American Chemical Society

Ren and Yamane
JOCArticle
SCHEME 1. Carbamoylation of Aryl Halides by Molybdenum
Carbonyl Amine Complexes
TABLE 2. Scope of Aryl Halides for Mo(CO)6-Mediated
Carbamoylation Reactiona
TABLE 1. Group VI Metal Carbonyl Complex-Mediated
Carbamoylation of Phenyl Iodidea
entry
M
x (equiv)
time (h)
yield (%)
1
W
W
Mo
Mo
Mo
1.0
1.0
1.0
0.2
12
20
3
3
3
90
13
97
97
85
2b
3
4
5
0.167
aThe reactions were carried out in the molar ratio of H2NBn/PhI/
NBu3 = 1.0:1.2:1.1. bReaction without Et4NCl.
can used as both carbon monoxide source and the catalyst as
well in the mechanistic cycle.6 We considered that the amount of
metal carbonyl complex could be reduced if the metal carbonyl
amine complex was generated in situ in the reaction con-
ditions. Herein, we present a simple and efficient amide synth-
esis with a low loading of Mo(CO)6, which is used as both the
catalyst and the carbon monoxide source.
Group VI metal amine carbonyl complexes are known
to be prepared from amine and (CO)5MClNEt4 (M = Cr,
Mo, W),7 which is readily obtained by subjecting M(CO)6 to
Et4NCl. Thus, we first examined carbamoylation of phenyl
iodide with M(CO)6 and amine (Table 1). When W(CO)6
(1 equiv) was treated with phenyl iodide and benzylamine in
the presence of Et4NCl and NBu3, 90% yield of amide 3aa
was obtained (entry 1). The yield of the amide was decreased
to 13% in the absence of Et4NCl (entry 2). The reaction with
Mo(CO)6 showed an efficient conversion and 3aa was obtained
in 97% yield (entry 3). Interestingly, the yield of 3aa was not
affected even when the amount of Mo(CO)6 was decreased
to 0.2 equiv (entry 4). It is noteworthy that 0.167 equiv of
Mo(CO)6, which involves a stoichiometric amount of CO,
gave 85% yield of amide 3aa (entry 5). These results explain
the high efficiency of the catalyst to incorporate its CO ligand
into the amide product.
aThe reactions were carried out with 1 (0.60 mmol), 2a (0.50 mmol),
and NBu3 (0.55 mmol) in diglyme at 150 °C unless otherwise stated. bThe
reaction temperature is 90 °C. cThe reaction temperature is 140 °C. dThe
reaction temperature is 120 °C. eThe reaction temperature is 80 °C. fThe
reaction temperature is 100 °C.
Results and Discussion
As we found that the carbamoylation of phenyl iodide
with 0.2 equiv of Mo(CO)6 sufficiently proceeded, we then
investigated the scope of aryl halides for this reaction (Table 2).
Regardless of the electronic property of the substituents and
substitution positions on the phenyl ring, the correspond-
ing amides were obtained in excellent yields (entries 1-5).
The naphthalenyl halides and heteroaromatic halides were also
applicable for this reaction, and the corresponding amides were
obtained (entries 6-11, 14, and 15). When 1-bromo-4-iodoben-
zene was used, selective carbamoylation proceeded to give
p-bromobenzamide 3ka (entry 12). Interestingly, when 2-chloro-
5-iodopyridine was used, N-benzyl-5-iodopicolinamide 3ja was
obtained as the product in 53% yield instead of the expected
(6) For oxidative addition of sp2-carbon halogen bond to molybdenum or
tungsten carbonyl complexes, see: (a) Richmond, T. G.; King, M. A.; Kelson,
E. P.; Arif, A. M. Organometallics 1987, 6, 1995. (b) Buffin, B. P.; Arif, A. M.;
Richmond, T. G. J. Chem. Soc., Chem. Commun. 1993, 1432.
(c) Kiplinger, J. L.; Richmond, T. G. Polyhedron 1997, 16, 409. (d) Sangu,
K.; Watanabe, T.; Takaya, J.; Iwasawa, N. Synlett 2007, 6, 929. (e) Takaya,
J.; Sangu, K.; Iwasawa, N. Angew. Chem., Int. Ed. 2009, 48, 7090.
(7) Schenk, W. A. J. Organomet. Chem. 1979, 179, 253.
J. Org. Chem. Vol. 75, No. 24, 2010 8411

Ren and Yamane
SCHEME 2. Mo(CO)6-Mediated Intramolecular
Aminocarbonylations
JOCArticle
TABLE 3. Scope of Amines for Mo(CO)6-Mediated Carbamoylation
Reactiona
TABLE 4. Using Aqueous Ammonia To Synthesize the Primary Amidea
aThe reactions were carried out with ArX (0.5 mmol) and aq. NH3
(ca. 1.5 mmol, 25-28% w/w) at 150 °C.
higher yield.9 The reaction with alkenyl halides 1o and 1p pro-
ceeded at lower temperatures (80-100 °C), to give the corre-
sponding R,β-unsaturated amides 3oa and 3pa in good yields
(entries 16-18). Although the yield was not so good, benzyl
bromide was also applicable for this reaction (entry 19).
Next, the scope of this reaction was examined with respect
to the amines (Table 3). N-Arylbenzamides 3ac, 3ad, and 3ae
were obtained in moderate to good yields when aniline deriva-
tives 2c-e were used (entries 3-5). Electron-rich aniline 2e gave
a better yield indicating that the nucleophilicity of anilines may
affect the reaction. Not only the aryl amines but also the alkyl
amines can be applied to give the corresponding amide in good
yields (entries 6-9). Cyclic secondary amines such as pyrrolidine
and piperidine as well as the acyclic secondary amines such as
methylbenzylamine and diethylamine can be used in this reac-
tion to provide good to excellent yields (entries 10-13). Hetero-
aromatic amines gave the corresponding amides in good yields
(entries 14-16).
aThe reactions were carried out in diglyme at 150 °C with 1a
(0.60 mmol), 2 (0.50 mmol), and NBu3 (0.55 mmol) unless otherwise
mentioned. bThe reaction was carried out with a 1:5 ratio of 1a (0.5 mmol)
and 2 (2.5 mmol). The reaction was carried out with a 1:2 ratio of 1a
(0.5 mmol) and 2 (1.0 mmol).
c
product, N-benzyl-6-chloronicotinamide (entry 11).8 3-Chloro-
pyridine, on the contrary, gave only a trace amount of amide 3la
despite longer reaction time (entry 13). These results suggest that
the chelation-assisted oxidative addition of 2-chloropyridine to
the molybdenum intermediate enhanced the reaction and gave
(8) For a review about palladium-catalyzed coupling reactions of aryl
chlorides, see: (a) Littke, A. F.; Fu, G. C. Angew. Chem., Int. Ed. 2002, 41,
4176. (b) Blaser, H.-U.; Indolese, A.; Naud, F.; Nettekoven, U.; Schnyder, A.
Adv. Synth. Catal. 2004, 346, 1583. For palladium-catalyzed aminocarbonyla-
tion of aryl chlorides, see: (c) Ben-David, Y.; Portnoy, M.; Milstein, D. J. Am.
Chem. Soc. 1989, 111, 8742. (d) Takeuchi, R.; Suzuki, K.; Sato, N. J. Mol. Catal.
1991, 66, 277. (e) Carpentier, J. F.; Petit, F.; Mortreux, A.; Dufaud, V.; Basset,
J. M.; Thivolle-Cazat, J. J. Mol. Catal. 1993, 81, 1. (f) Perry, R. J.; Wilson, B. D.
J. Org. Chem. 1996, 61, 7482. (g) Kim, J. S.; Sen, A. J. Mol. Catal. A 1999, 143,
We applied this Mo(CO)6-mediated carbamoylation reac-
tion for the lactam synthesis via intramolecular aminocar-
bonylation. Primary amines 2q and 2r that contain a
2-iodoaryl moiety were prepared and subjected to the reaction
conditions to give five- and six-membered ring lactams 3q and 3r
in good yields (Scheme 2).
€
197. (h) Magerlein, W.; Indolese, A. F.; Beller, M. Angew. Chem., Int. Ed. 2001,
40, 2856. (i) Calo, V.; Giannoccaro, P.; Nacci, A.; Monopoli, A. J. Organomet.
Chem. 2002, 645, 152. (j) Lagerlund, O.; Larhed, M. J. Comb. Chem. 2006, 8, 4.
(k) Martinelli, J. R.; Clark, T. P.; Watson, D. A.; Munday, R. H.; Buchwald,
S. L. Angew. Chem., Int. Ed. 2007, 46, 8460.
(9) For references related to chelation assisted oxidative addition of Ar-X
to tungsten or molybdenum carbonyl complexes, see refs 6a, 6b, 6c, and 6e.
8412 J. Org. Chem. Vol. 75, No. 24, 2010

Ren and Yamane
JOCArticle
SCHEME 3. Proposed Mechanisma
yet to be elucidated, it is noteworthy that molybdenum carbonyl
species acts as the catalyst and most of the carbonyl ligands on
the molybdenum center are incorporated into the product.
Conclusions
In conclusion, we have established an efficient molybde-
num-mediated carbamoylation of aryl halides. The proce-
dure is simple and requires only slight excess of carbon
monoxide in the form of Mo(CO)6. This reaction provides a
method for synthesis of a variety of amides. Primary amides are
also prepared in the reaction with aqueous ammonia.
Experimental Section
General Procedure for Mo(CO)6-Mediated Carbamoylation of
Aryl Halides. A mixture of aryl halide 1 (0.60 mmol), amnie
complex 2(0.50 mmol), Mo(CO)6 (0.10 mmol), NEt4Cl(0.1mmol),
and NBu3 (0.55 mmol) in diglyme (5 mL) was heated at 150 °C
under N2 atmosphere. The reaction was monitored by thin-layer
chromatography. The volatile materials were removed under the
reduced pressure, and the residue was purified by flash column
chromatography (SiO2, hexane/ethyl acetate = 8:1) to afford the
pure amide products.
an = 5, 4, 3, and 2 for the first, second, third, and fourth cycles, respec-
tively. L = X-, Cl-, HNR2, -NR2, 1,4-diglyme, or CO.
Finally, we also applied this Mo(CO)6-mediated carba-
moylation to the synthesis of primary amides. To the best of our
knowledge, there is no example reported on the synthesis of
primary amides by the conventional palladium-catalyzed three-
component coupling reaction by means of aqueous ammonia,
which is the most readily available ammonia source.10,11 This is
because the palladium catalysts may be deactivated in the
reaction conditions with aqueous ammonia.
We attempted Mo(CO)6-mediated carbamoylation of organic
halides with aqueous ammonia as summarized in Table 4. When
phenyl iodide was treated with aqueous ammonia in the pres-
ence of 0.2 equiv of Mo(CO)6, benzamide was obtained in 91%
yield (entry 1).12 The reaction proceeded at ambient pressure,
and hence special apparatus such as a sealed tube or autoclave
is not necessary. Both electron-rich and -deficient aryl iodides
1b and 1e afforded the corresponding primary amides 3bq
and 3eq in moderate yields (entries 2 and 3). 3-Bromothiophene
was also used in this reaction to afford amide 3hq in 54% yield
(entry 4). Cinnamamide (3oq) was obtained in good yield when
β-bromostyrene (1o) was used (entry 5).
1
N-Benzylbenzamide (3aa).13 White solid; H NMR (CDCl3,
400 MHz) δ 4.65 (d, J = 6.0 Hz, 2H), 6.42 (br s, 1H), 7.28-7.37
(m, 5H), 7.41-7.45 (dd, J = 7.6 Hz, 7.2 Hz, 2H), 7.48-7.52 (t, J =
7.2 Hz, 1H), 7.79 (d, J= 7.2 Hz, 2H); 13CNMR(CDCl3, 100MHz)
δ 44.1, 126.9, 127.6, 127.9, 128.6, 128.8, 131.5, 134.4, 138.1, 167.3.
N-Benzyl-4-methoxybenzamide (3ba).14 White solid; 1H
NMR (CDCl3, 500 MHz) δ 3.74 (s, 3H), 4.51 (d, J = 5.5 Hz,
2H), 6.50 (br s, 1H), 6.80 (d, J = 8.5 Hz, 2H), 7.18-7.27 (m, 5H),
7.68 (d, J = 9.0 Hz, 2H); 13C NMR (CDCl3, 125 MHz) δ (ppm)
44.0, 55.3, 113.7, 126.6, 127.4, 127.8, 128.7, 128.8, 138.4, 162.1, 166.9.
N-Benzyl-3-methoxybenzamide (3ca).15 Colorless oil; 1H
NMR (CDCl3, 400 MHz) δ 3.80 (s, 3H), 4.59 (d, J = 6.0 Hz,
2H), 6.70 (br s, 1H), 6.99-7.02 (m, 1H), 7.25-7.39 (m, 8H); 13
C
NMR (CDCl3, 100 MHz) δ (ppm) 44.0, 55.3, 112.3, 117.7, 118.7,
127.5, 127.8, 128.7, 129.5, 135.8, 138.1, 159.7, 167.2.
N-Benzyl-2-methoxybenzamide (3da).16 Colorless oil; 1H
NMR (CDCl3, 400 MHz) δ 3.89 (s, 3H), 4.68 (d, J = 5.6 Hz,
2H), 6.95 (d, J = 8.4 Hz, 1H), 7.08 (t, J = 7.6 Hz, 1H),
7.25-7.37 (m, 5H), 7.41-7.46 (m, 1H), 8.21 (br s, 1H), 8.25
(dd, J = 7.6, 1.6 Hz, 1H); 13C NMR (CDCl3, 100 MHz) δ (ppm)
43.6, 55.8, 111.2, 121.2, 121.3, 127.1, 127.4, 128.5, 132.3, 132.7,
138.7, 157.4, 165.2.
Two possible mechanisms are depicted in Scheme 3. One
of the plausible pathways involves oxidative addition of aryl
halide and a subsequent insertion of carbon monoxide to
generate acylmolybdenum intermediate A. Alternatively,
carbamoylmolybdenum intermediate B would be generated by
nucleophilic attack of amine to the carbonyl ligand followed by
oxidative addition of aryl halide. Although the mechanism has
1
4-Acetyl-N-benzylbenzamide (3ea).17 White solid; H NMR
(CDCl3, 400 MHz) δ 2.60 (s, 3H), 4.63 (d, J = 5.6 Hz, 2H), 6.75
(brs, 1H), 7.28-7.35 (m, 5H), 7.86 (d, J= 8.4 Hz, 2H), 7.96 (d, J=
8.0 Hz, 2H); 13C NMR (CDCl3, 100 MHz) δ (ppm) 26.7, 44.2,
127.3, 127.7, 127.9, 128.5, 128.8, 137.8, 138.2, 139.1, 166.4, 197.4.
N-Benzylnaphthalene-1-carboxamide (3fa).18 White solid; 1H
NMR (CDCl3, 400 MHz) δ 4.70 (d, J = 5.6 Hz, 2H), 6.39 (br s,
1H), 7.28-7.43 (m, 6H), 7.49-7.60 (m, 3H), 7.85-7.91 (m, 2H),
8.33-8.35 (m, 1H); 13C NMR (CDCl3, 100 MHz) δ 44.1, 124.6,
124.9, 125.4, 126.4, 127.1, 127.6, 127.8, 128.3, 128.8, 130.1, 130.6,
133.6, 134.2, 138.1, 169.4.
(10) For palladium-catalyzed aminocarbonylation reactions by using
water as the solvent, see: (a) Wu, X.; Larhed, M. Org. Lett. 2005, 7, 3327.
(b) Wu, X.; Ekegren, J. K.; Larhed, M. Organometallics 2006, 25, 1434.
(c) Tambade, P. J.; Patil, Y. P.; Bhanushali, M. J.; Bhanage, B. M. Synthesis
2008, 15, 2347.
(11) For Pd-catalyzed primary amides preparation, see: (a) Morera, E.;
Ortar, G. Tetrahedron Lett. 1998, 39, 2835. (b) Schnyder, A.; Beller, M.;
Mehltretter, G.; Nsenda, T.; Studer, M.; Indolese, A. F. J. Org. Chem. 2001,
66, 4311. (c) Shen, Q.; Hartwig, J. F. J. Am. Chem. Soc. 2006, 128, 10028.
N-Benzylnaphthalene-2-carboxamide (3ga).18 White solid; 1H
NMR (CDCl3, 500 MHz) δ 4.67 (d, J = 6.0 Hz, 2H), 6.90
ꢀ
€
ꢀ
(d) Takacs, E.; Varga, C.; Skoda-Foldes, R.; Kollar, L. Tetrahedron Lett.
ꢀ
(13) Katritzky, A. R.; Cai, C.-M.; Singh, S. K. J. Org. Chem. 2006, 71,
3375.
ꢀ
ꢀ
€
2007, 48, 2453. (e) Balogh, J.; Maho, S.; Hada, V.; Kollar, L.; Skoda-Foldes,
R. Synthesis 2008, 19, 3040.
(14) Yamazaki, K.; Kondo, Y. J. Comb. Chem. 2004, 6, 121.
(15) Agwada, V. C. J. Chem. Eng. Data 1982, 27, 479.
(16) Martinelli, J. R.; Watson, D. A.; Freckmann, D. M. M.; Barder,
T. E.; Buchwald, S. L. J. Org. Chem. 2008, 73, 7102.
(17) Ren, W.; Yamane, M. J. Org. Chem. 2009, 74, 8332.
(18) Ragnarsson, U.; Grehn, L.; Maia, H. L. S.; Monteiro, L. S. J. Chem.
Soc., Perkin Trans. 1. 2002, 97.
(12) The absence of Et4NCl did not lower the yield of primary amide.
Although we are not sure the role of Et4NCl in the reaction of primary and
secondary amine, chloride anion may coordinate to the molybdenum center
and stabilize the intermediates. In the reaction with aqueous ammonia,
ammonia or water molecule may coordinate and stabilize the molybdenum
intermediate instead of chloride anion.
J. Org. Chem. Vol. 75, No. 24, 2010 8413

Ren and Yamane
JOCArticle
(br s, 1H), 7.28-7.38 (m, 5H), 7.49-7.56 (m, 2H), 7.84-7.87
(m, 4H), 8.31 (s, 1H); 13C NMR (CDCl3, 125 MHz) δ 44.1,
123.6, 126.6, 127.4, 127.5, 127.6, 127.7, 127.8, 128.4, 128.69,
128.8, 131.5, 132.5, 134.7, 138.2, 167.5.
1215, 771, 667 cm-1; 1H NMR (CDCl3, 400 MHz) δ 2.42-2.45
(m, 2H), 2.82-2.84 (m, 2H), 4.51 (d, J = 5.8 Hz, 2H), 6.46
(s, 1H), 7.03 (br s, 1H), 7.25-7.34 (m, 5H); 13C NMR (CDCl3,
100 MHz) δ (ppm) 27.7, 35.2, 43.7, 127.7, 127.8, 128.7, 133.4,
137.3, 163.9, 168.3, 209.3. ESIHRMS found: m/z 216.1025.
Calcd for C13H14NO2: (M þ H)þ 216.1025.
N-Benzylthiophene-3-carboxamide (3ha).17 White solid; 1H
NMR (CDCl3, 500 MHz) δ 4.57 (d, J = 5.5 Hz, 2H), 6.61
(br s, 1H), 7.26-7.35 (m, 6H), 7.39-7.41 (m, 1H), 7.87-7.88
(m, 1H); 13C NMR (CDCl3, 125 MHz) δ (ppm) 43.7, 126.1,
126.4, 127.5, 127.8, 128.3, 128.7, 137.2, 138.2, 163.0.
1
N-Benzyl-2-phenylacetamide (3ra).21 White solid; H NMR
(CDCl3, 500 MHz) δ 3.59 (s, 2H), 4.38 (d, J = 5.5 Hz, 2H), 5.90
(br s, 1H), 7.16 (d, J = 7.0 Hz, 2H), 7.22-7.34 (m, 8H); 13C
NMR (CDCl3, 125 MHz) δ (ppm) 43.5, 43.7, 127.28, 127.33,
127.4, 128.6, 128.9, 129.4, 134.8, 138.1, 170.9.
N-Benzylpyridine-2-carboxamide (3ia).18 White solid; 1H
NMR (CDCl3, 500 MHz) δ 4.68 (d, J = 6.0 Hz, 2H), 7.27-
7.30 (m, 1H), 7.33-7.39 (m, 4H), 7.41-7.44 (m, 1H), 7.84-7.87
(m, 1H), 8.23-8.25 (m, 1H), 8.39 (br, s, 1H), 8.52-8.53 (m, 1H);
13C NMR (CDCl3, 125 MHz) δ (ppm) 43.5, 122.3, 126.2, 127.5,
127.8, 128.7, 137.4, 138.2, 148.1, 149.8, 164.2.
N-(4-Methoxybenzyl)benzamide (3ab).22 White solid; 1H
NMR (CDCl3, 400 MHz) δ 3.77 (s, 3H), 4.52 (d, J = 5.6 Hz, 2H),
6.69 (br s, 1H), 6.85 (d, J = 8.3 Hz, 2H), 7.24 (d, J = 8.3 Hz, 2H),
7.38-7.48 (m, 3H), 7.77 (d, J = 7.9 Hz, 2H); 13C NMR (CDCl3,
100 MHz) δ (ppm) 43.5, 55.2, 114.0, 126.9, 128.4, 129.2, 130.3,
131.4, 134.4, 158.9, 167.3.
N-Benzyl-5-iodopyridine-2-carboxamide (3ja). White solid; mp
76-77 °C (AcOEt); IR (NaCl, CHCl3) 3392, 3018, 2399, 1670, 1523,
1
1456, 1215, 759, 669 cm-1; H NMR (CDCl3, 400 MHz) δ 4.65
1
N-Phenylbenzamide (3ac).23 White solid; H NMR (CDCl3,
(d, J = 6.0 Hz, 2H), 7.27-7.35 (m, 5H), 7.99 (d, J = 8.0 Hz, 1H),
8.17 (dd, J = 2.0, 8.0 Hz, 1H), 8.26 (br s, 1H), 8.72 (d, J = 2.0 Hz,
1H); 13C NMR (CDCl3, 100 MHz) δ (ppm) 43.5, 97.0, 124.0, 127.5,
127.8, 128.7, 137.9, 145.7, 148.6, 154.1, 163.7. ESIHRMS found:
m/z 338.9981. Calcd for C13H12IN2O: (M þ H)þ 338.9994.
400 MHz) δ 7.15 (t, J = 7.6 Hz, 1H), 7.36 (t, J = 7.6 Hz, 2H),
7.45-7.56 (m, 3H), 7.65 (d, J = 7.6 Hz, 2H), 7.86 (d, J = 7.6 Hz,
2H), 7.95 (br s, 1H); 13C NMR (CDCl3, 100 MHz) δ (ppm)
120.2, 124.5, 127.0, 128.7, 129.0, 131.8, 135.0, 137.9, 165.8.
Methyl 4-Benzamidobenzoate (3ad).24 White solid; 1H NMR
(CDCl3, 400 MHz) δ 3.92 (s, 3H), 7.49-7.60 (m, 3H), 7.75 (d, J =
8.2 Hz, 2H), 7.88 (d, J = 7.2 Hz, 2H), 7.99 (br s, 1H), 8.06 (d, J =
8.8 Hz, 2H); 13C NMR (CDCl3, 100 MHz) δ (ppm) 52.1, 119.2,
125.9, 127.1, 128.9, 130.9, 132.2, 134.5, 142.1, 165.8, 166.6.
N-(4-Methoxyphenyl)benzamide (3ae).25 White solid; 1H
NMR (CDCl3, 400 MHz) δ 3.82 (s, 3H), 6.91 (d, J = 9.2 Hz, 2H),
7.47-7.56 (m, 5H), 7.73 (br s, 1H), 7.86 (d, J = 7.6 Hz, 2H); 13C
NMR (CDCl3, 100 MHz) δ (ppm) 55.5, 114.2, 122.1, 127.0, 128.7,
131.0, 131.7, 135.0, 156.6, 165.6.
1
N-Benzyl-4-bromobenzamide (3ka).19 White solid; H NMR
(CDCl3, 300 MHz) δ 4.61 (d, J = 5.7 Hz, 2H), 6.50 (br s, 1H),
7.29-7.38 (m, 5H), 7.55 (d, J = 8.4 Hz, 2H), 7.65 (d, J = 8.7 Hz,
2H); 13C NMR (CDCl3, 75 MHz) δ (ppm) 44.2, 126.2, 127.7,
127.9, 128.6, 128.8, 131.8, 133.2, 137.9, 166.4.
N-Benzylquinoline-2-carboxamide (3ma). White solid; mp
124-125 °C (AcOEt); IR (NaCl, CHCl3) 3388, 3014, 1670,
1529, 1500, 1427, 1217, 846, 771, 667 cm-1; 1H NMR (CDCl3,
400 MHz) δ 4.73 (d, J = 6.4 Hz, 2H), 7.24-7.40 (m, 5H), 7.57
(t, J = 7.6 Hz, 1H), 7.71 (t, J = 7.6 Hz, 1H), 7.84 (d, J = 8.0 Hz,
1H), 8.05 (d, J = 8.4 Hz, 1H), 8.27 (d, J = 8.4 Hz, 1H), 8.34
(d, J= 8.4 Hz, 1H), 8.64 (br s, 1H); 13CNMR(CDCl3, 100MHz) δ
(ppm) 43.5, 118.8, 127.4, 127.6, 127.77, 127.79, 128.6, 129.2, 129.5,
130.0, 137.4, 138.2, 146.4, 149.6, 164.4. ESIHRMS found: m/z
263.1176. Calcd for C17H15N2O: (M þ H)þ 263.1184.
N-Butylbenzamide (3af).26 Light yellow oil; 1H NMR (CDCl3,
400 MHz) δ 0.90 (t, J = 7.6 Hz, 3H), 1.35 (qt, J = 7.2, 7.6 Hz, 2H),
1.55 (tt, J = 7.2 Hz, 2H), 3.39 (dt, J = 6.8, 6.4 Hz, 2H), 6.65
(br s, 1H), 7.33-7.45 (m, 3H), 7.75 (d, J = 6.8 Hz, 2H); 13C NMR
(CDCl3, 100 MHz) δ (ppm) 13.7, 20.0, 31.6, 39.7, 126.8, 128.3,
131.1, 134.7, 167.6.
N-Benzyl-4,6-dimethoxy-1,3,5-triazine-2-carboxamide (3na).
White solid; mp 112-114 °C (AcOEt); IR (NaCl, CHCl3)
3437, 3265, 3016, 2399, 1570, 1467, 1377, 1219, 1143, 1111,
819, 781, 667 cm-1; 1H NMR (CDCl3, 400 MHz) δ 3.89 (s, 3H),
3.95 (s, 3H), 4.64 (d, J = 6.12 Hz, 2H), 6.89 (br s, 1H), 7.25-7.32
(m, 5H); 13C NMR (CDCl3, 100 MHz) δ (ppm) 44.7, 54.4, 54.6,
127.2, 127.5, 128.4, 138.4, 168.1, 171.9, 172.4. ESIHRMS found:
m/z 275.1140. Calcd for C13H15N4O3: (M þ H)þ 275.1144.
(E)-N-Benzylcinnamamide (3oa).20 White solid; 1H NMR
(CDCl3, 400 MHz) δ 4.53 (d, J = 4.0 Hz, 2H), 6.49 (br s, 1H),
6.49 (d, J = 15.6 Hz, 1H), 7.27-7.47 (m, 10H), 7.668 (d, J =
15.6 Hz, 1H); 13C NMR (CDCl3, 100 MHz) δ (ppm) 43.7, 120.5,
127.4, 127.7, 127.8, 128.6, 128.7, 129.6, 134.7, 138.2, 141.2, 165.9.
(E)-N-Benzyl-3-[4-(trifluoromethyl)phenyl]acrylamide (3pa).
White solid; mp 163-165 °C (AcOEt); IR (NaCl, CHCl3) 3263,
3018, 1666, 1627, 1512, 1415, 1323, 1215, 1168, 1130, 1068, 756,
669 cm-1; 1H NMR (CDCl3, 400 MHz) δ 4.56 (d, J = 5.8 Hz, 2H),
6.20 (br s, 1H), 6.50 (d, J = 15.6 Hz, 1H), 7.27-7.36 (m, 5H), 7.57
(dd, J = 8.4, 16.0 Hz, 4H), 7.67 (d, J = 15.6 Hz, 1H); 13C NMR
(CDCl3, 100 MHz) δ (ppm) 43.9, 122.5, 122.9, 125.2, 125.76 (q, J =
3.7 Hz), 127.7, 127.9, 128.8, 131.3 (q, J = 32.4 Hz), 137.9, 138.2,
139.7, 165.1. ESIHRMS found: m/z 306.1110. Calcd for
C17H15N3OF3: (M þ H)þ 306.1106.
N-tert-Butylbenzamide (3ag).27 White solid; 1H NMR
(CDCl3, 400 MHz) δ 1.46 (s, 9H), 5.99 (br s, 1H), 7.38-7.45
(m, 3H), 7.70 (d, J = 7.4 Hz, 2H); 13C NMR (CDCl3, 100 MHz) δ
(ppm) 28.8, 51.5, 126.6, 128.4, 131.0, 135.9, 166.9.
N-Cyclopropylbenzamide (3ah).28 White solid; 1H NMR
(CDCl3, 400 MHz) δ 0.59-0.63 (m, 2H), 0.81-0.86 (m, 2H),
2.85-2.91 (m, 1H), 6.49 (br s, 1H), 7.36-7.48 (m, 3H), 7.73
(d, J = 7.6 Hz, 2H); 13C NMR (CDCl3, 100 MHz) δ (ppm) 6.6,
23.1, 126.8, 128.4, 131.3, 134.3, 168.9.
N-Cyclohexylbenzamide (3ai).29 White solid; 1H NMR
(CDCl3, 400 MHz) δ 1.10-1.43 (m, 5H), 1.59-1.75 (m, 3H),
1.97-2.00 (m, 2H), 3.89-3.98 (m, 1H), 6.23 (br s, 1H),
7.35-7.46 (m, 3H), 7.74 (d, J = 7.2 Hz, 2H); 13C NMR (CDCl3,
100 MHz) δ (ppm) 24.9, 25.4, 33.1, 48.6, 126.8, 128.3, 131.1, 135.0,
166.6.
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(21) Lee, H.-L.; Aube, J. Tetrahedron 2007, 63, 9007.
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2005, 61, 12153.
(23) Zhang, Z. H.; Yu, Y.; Liebeskind, L. S. Org. Lett. 2008, 10, 3005.
(24) Gould, S.; Laufer, D. A. J. Magn. Reson. 1979, 34, 37.
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R.; Saha, P.; Punniyamurthy, T. J. Org. Chem. 2009, 74, 1971.
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Chem. 2004, 69, 8340.
N-Benzyl-3-oxocyclopent-1-ene-1-carboxamide (3qa). Color-
less oil, IR (NaCl, CHCl3) 3321, 3016, 1712, 1653, 1602, 1521,
(27) Baum, J. C.; Milne, J. E.; Murry, J. A.; Thiel, O. R. J. Org. Chem.
2009, 74, 2207.
(19) Petricci, E.; Mugnaini, C.; Radi, M.; Corelli, F.; Botta, M. J. Org.
Chem. 2004, 69, 7880.
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hedron 2000, 56, 979.
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Yasuda, N.; Mase, T. Org. Lett. 2008, 10, 1653.
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6358.
8414 J. Org. Chem. Vol. 75, No. 24, 2010

Ren and Yamane
JOCArticle
1-Benzoylpyrrolidine (3aj).30 Light yellow solid; 1H NMR
(CDCl3, 400 MHz) δ 1.83-1.99 (m, 4H), 3.42 (t, J = 6.4 Hz,
2H), 3.64 (t, J = 6.8 Hz, 2H), 7.38-7.51 (m, 5H); 13C NMR
(CDCl3, 100 MHz) δ (ppm) 24.4, 26.4, 46.1, 49.6, 127.0, 128.2,
129.7, 137.2, 169.7.
(d, J =7.8 Hz, 1H), 8.23 (br s, 1H);13CNMR (CDCl3, 100 MHz) δ
(ppm) 45.8, 123.1, 123.6, 127.9, 131.6, 132.2, 143.7, 172.3.
1,2,3,4-Tetrahydroisoquinolin-1-one (3r).38 White solid; 1H
NMR (CDCl3, 400 MHz) δ 2.93 (t, J = 6.4 Hz, 2H), 3.49-
3.53 (m, 2H), 6.65 (br s, 1H), 7.14-7.19 (m, 1H), 7.26-7.30
(m, 1H), 7.36-7.40 (m, 1H), 7.99 (d, J = 7.6 Hz, 1H); 13C NMR
(CDCl3, 100 MHz) δ (ppm) 28.3, 40.2, 127.0, 127.2, 127.9, 128.9,
132.1, 138.8, 166.4.
1-Benzoylpiperidine (3ak).31 Colorless oil; 1H NMR (CDCl3,
400 MHz) δ 1.48 (br s, 2H), 1.65 (br s, 4H), 3.31 (br s, 2H), 3.68
(br s, 2H), 7.36 (br s, 5H); 13C NMR (CDCl3, 100 MHz) δ (ppm)
24.5, 25.5, 26.4, 43.0, 48.7, 126.7, 128.3, 129.2, 136.4, 170.2.
N-Benzyl-N-methylbenzamide (3al).32 Colorless oil; 1H NMR
(CDCl3, 400 MHz) δ 2.86 (br s, 1.5H), 3.03 (br s, 1.5H), 4.51
(br s, 1H), 4.76 (br s, 1H), 7.17-7.47 (m, 10H); 13C NMR (CDCl3,
100 MHz) δ (ppm) 33.1, 36.9, 50.7, 55.1, 126.7, 126.9, 127.4, 128.1,
128.4, 128.6, 128.7, 129.5, 136.2, 136.5, 136.9, 171.5, 172.2.
N,N-Diethylbenzamide (3am).33 Colorless oil; 1H NMR
(CDCl3, 400 MHz) δ 1.09 (br s, 3H), 1.23 (br s, 3H), 3.23
(br s, 2H), 3.53 (br s, 2H), 7.36 (br s, 5H); 13C NMR (CDCl3,
100 MHz) δ (ppm) 12.8, 14.2, 39.2, 43.2, 126.2, 128.3, 129.0,
137.2, 171.3.
Benzamide (3aq).39 White solid; 1H NMR (CDCl3, 400 MHz)
δ 6.21 (br s, 2H), 7.44 (t, J = 7.6 Hz, 2H), 7.53 (t, J = 7.6 Hz,
1H), 7.81 (d, J = 7.6 Hz, 2H); 13C NMR (CDCl3, 100 MHz)
δ (ppm) 127.3, 128.6, 132.0, 133.3, 169.6.
4-Methoxybenzamide (3bq).40 White solid; 1H NMR
(DMSO-d6, 400 MHz) δ 3.79 (s, 3H), 6.97 (d, J = 8.8 Hz, 2H),
7.86 (d, J = 8.8 Hz, 3H); 13C NMR (DMSO-d6, 100 MHz) δ (ppm)
55.3, 113.4, 126.5, 129.4, 161.6, 167.5.
4-Acetylbenzamide (3eq).41 White solid; 1H NMR (DMSO-d6,
400 MHz) δ 2.61 (s, 3H), 7.57 (br s, 1H), 8.00 (s, 4H), 8.18
(br s, 1H); 13C NMR (DMSO-d6, 100 MHz) δ (ppm) 27.0, 127.8,
128.1, 138.1, 138.7, 167.2, 197.8.
1-Benzoyl-1H-pyrrole (3an).34 Colorless oil, 1H NMR
(CDCl3, 400 MHz) δ 6.35 (m, 2H), 7.29 (m, 2H), 7.49-7.63
(m, 3H), 7.75 (d, J = 7.6 Hz, 2H); 13C NMR (CDCl3, 100MHz) δ
(ppm) 113.1, 121.3, 128.5, 129.5, 132.3, 133.2, 167.7.
Thiophene-3-carboxamide (3hq).42 White solid; 1H NMR
(DMSO-d6, 400 MHz) δ 7.25 (br s, 1H), 7.48-7.56 (m, 2H),
7.79 (br s, 1H), 8.13 (d, J = 1.6 Hz, 1H); 13C NMR (DMSO-d6,
100 MHz) δ (ppm) 126.6, 127.2, 129.1, 138.0, 163.8.
Cinnamamide (3oq).43 White solid; 1H NMR (CDCl3, 400
MHz) δ 5.65 (br s, 2H), 6.46 (d, J = 15.6 Hz, 1H), 7.37-7.38
(m, 3H), 7.51-7.53 (m, 2H), 7.65 (d, J = 15.6 Hz, 1H); 13C
NMR (CDCl3, 100 MHz) δ (ppm) 119.5, 127.9, 128.8, 130.0,
134.5, 142.5, 167.9.
1
N-Benzoyl-1H-indole (3ao).35 White solid; H NMR (CDCl3,
400 MHz) δ6.62(d, J= 7.6 Hz, 1H), 7.29-7.39(m, 3H),7.41-7.62
(m, 4H), 7.74 (d, J = 7.6 Hz, 2H), 8.40 (d, J = 8.4 Hz, 1H); 13
C
NMR (CDCl3, 100 MHz) δ (ppm) 108.5, 116.4, 120.9, 123.9, 124.9,
127.6, 128.6, 129.2, 130.8, 131.9, 134.6, 136.0, 168.7.
N-Benzoyl-9H-carbazole (3ap).36 White solid; 1H NMR
(CDCl3, 400 MHz) δ 7.32-7.38 (m, 4H), 7.52-7.55 (m, 4H), 7.66
(t, J = 7.2 Hz, 1H), 7.74 (d, J = 7.6 Hz, 2H), 8.02 (d, J = 8.0 Hz,
2H); 13C NMR (CDCl3, 100 MHz) δ (ppm) 115.7, 119.8, 123.4,
126.0, 126.7, 128.9, 129.0, 132.3, 135.7, 139.1, 169.6.
Acknowledgment. We thank Nanyang Technological
University for the generous financial support.
2,3-Dihydro-1H-isoindol-1-one (3q).37 White solid; 1H NMR
(CDCl3, 400 MHz) δ 4.47 (s, 2H), 7.45-7.58 (m, 3H), 7.86
Supporting Information Available: General experimental
procedures for the synthesis of compounds 3 and spectral data
for the amide products. This material is available free of charge
via the Internet at http://pubs.acs.org.
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J. Org. Chem. Vol. 75, No. 24, 2010 8415