Palladium-Catalyzed Aminocarbonylation of Aryl Halides with 2,4,6-Trichloro-1,3,5-triazine/Formamide Mixed Reagent

Article abstract of DOI:10.1002/ejoc.201501607

In this work, the mixture of formamide and 2,4,6-trichloro-1,3,5-triazine (cyanuric chloride or TCT) is introduced as a new amidating agent in Pd-catalyzed aminocarbonylation of aryl halides. In the presence of a catalytic amount of palladium and TCT/formamide reagent, a range of aryl halides (X = Cl, Br, I) were converted into amides efficiently in N,N-dimethylformamide at 120 °C. The 2,4,6-trichloro-1,3,5-triazine/formamide mixed reagent was found to be an efficient amidating agent in Pd-catalyzed aminocarbonylation of aryl halides. In the presence of this reagent and a catalytic amount of Pd, a range of amides were synthesized by using aryl halides.

Full text of DOI:10.1002/ejoc.201501607

DOI: 10.1002/ejoc.201501607
Full Paper
Aminocarbonylation
Palladium-Catalyzed Aminocarbonylation of Aryl Halides with
2,4,6-Trichloro-1,3,5-triazine/Formamide Mixed Reagent
Nasser Iranpoor,*[a] Farhad Panahi,*[a,b] Fatemeh Roozbin,[a] Soodabeh Erfan,[a] and
Sajjad Rahimi[a]
Abstract: In this work, the mixture of formamide and 2,4,6- dium and TCT/formamide reagent, a range of aryl halides (X =
trichloro-1,3,5-triazine (cyanuric chloride or TCT) is introduced
as a new amidating agent in Pd-catalyzed aminocarbonylation
of aryl halides. In the presence of a catalytic amount of palla-
Cl, Br, I) were converted into amides efficiently in N,N-dimethyl-
formamide at 120 °C.
Introduction
Aminocarbonylation of aryl halides is one of the interesting
strategies in amide synthesis. In this protocol, carbon monoxide
and amine in the presence of a transition metal is converted
into the amide. Since the discovery of this valuable reaction by
Heck, many modifications have been developed to improve its
applicability in amide synthesis.[1] Most of these modifications
rely on the application of new carbonyl and amine sources.
Some of the reported methodologies are shown in Scheme 1.
In most cases, a stoichiometric amount of carbon monoxide
from different CO-precursors is used to prepare amides.[2] Given
that toxic carbon monoxide is often required in excess, chemists
have devised alternative methods that avoid its direct use.[3] To
remove the practical problems associated with the use of
carbon monoxide, metal carbonyl compounds [Mn(CO)m] have
been developed for the generation of CO gas in situ. However,
toxicity of metal carbonyls and harsh reaction conditions are
the main disadvantages of this strategy.[4] Carbamoylstannanes
and carbamoylsilanes were also used in aminocarbonylation re-
actions, however the thermal instability of these reagents is the
main limitation of this method.[5] In other reports, N,N-dimethyl-
formamide (DMF) was used as the source of the carbonyl group
in aminocarbonylation of aryl halides in the presence of an
amine.[6] Formamide was also used as an ammonia synthon in
aminocarbonylation reactions.[7] This reagent can also be used
as amidating agent in the absence of amine.[8] However, this
transformation requires high temperature and strongly basic
conditions. The use of DMF as amide source in the presence of
POCl3 was reported in CO-free aminocarbonylation of aryl and
Scheme 1. Some of the methodologies used for aminocarbonylation of aryl
halides. Replacing CO by metal carbonyl compounds, carbamoylstannanes,
carbamoylsilanes, DMF, and CHCl3.
alkenyl halides through the formation of the Vilsmeier immin-
ium intermediate.[9] The use of excess POCl3 to form the inter-
mediate is a limitation of this methodology. Recently, our group
reported that WCl6/DMF is an efficient system for amidation of
aryl halides.[10] The reaction was accomplished in the presence
of 2.5 mol-% PdCl2 at 140 °C. The WCl6 reagent is responsible
for the generation of both Pd0 catalyst as well as the formation
of a Vilsmeier iminium type intermediate. Overall, harsh condi-
tions were needed to perform this reaction. Very recently,
chloroform was used as a source of CO in the aminocarbonyl-
ation of aryl iodides and bromides in the presence of a Pd-
catalyst system.[11] In this methodology, the reaction was per-
formed in the presence of PdCl2 as catalyst, DPEphos as ligand,
and CsOH (10 equimolar) as base in toluene at 80 °C for 24 h.
In a continuation of our previous work on 2,4,6-trichloro-
1,3,5-triazine (cyanuric chloride or TCT) reagent,[12] herein, we
[a] Chemistry Department, College of Sciences, Shiraz University,
Shiraz 71454, Iran
E-mail: iranpoor@susc.ac.ir
[b] Department of Polymer Engineering and Color Technology,
Amirkabir University of Technology,
Tehran, Iran
E-mail: fpanahi@aut.ac.ir
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/ejoc.201501607.
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disclosed the use of TCT/DMF mixed reagent for aminocarbon-
ylation of aryl halides in the presence of a Pd catalyst system.
To our knowledge, there is no report on the use of TCT/DMF
as amidating agent in Pd-catalyzed aminocarbonylation of aryl
halides.
Results and Discussion
Although the TCT/DMF salt was previously synthesized, herein
we detail some additional information about the structure of
this reagent. The TCT/DMF mixed reagent as amidating reagent
is produced by simply reacting TCT and DMF at room tempera-
ture. DMF immediately reacts with TCT and forms a white pow-
der, which is stable under ambient conditions. The possible
chemical structures of this salt are shown in Scheme 2.
All of the chemical structures (especially B and C) can act as
amidating agents.[13] It should be mentioned that the chemical
structures proposed for this reagent are formed at room tem-
perature and there are other suggested structures for higher
temperatures.[13a,14] In this study, the formed reagent at room
temperature was characterized by using 1H NMR, 13C NMR, and
FTIR spectroscopy. A comparison between the 1H NMR and
13C NMR spectra of TCT/DMF and those of the starting materials
is shown in Figure 1. Signals for DMF, which was used in excess,
also appear in the spectra of the TCT/DMF mixture. A singlet at
δ = 8.71 ppm appears for the vinylic H-atom of the TCT/DMF
regent and a 0.8 ppm downfield shift relative to DMF shows
the iminium nature of this salt. The methyl groups of this rea-
gent also appear at higher chemical shift relative to those of
the methyl groups of DMF.
Figure 1. Comparison of 1H NMR spectra of DMF and the TCT/DMF mixture
(a). The 13C NMR spectra of TCT, DMF, and TCT/DMF regent (b).
stead, new peaks were observed for the TCT/DMF mixed rea-
gent system.
The combination of TCT and DMF generates a stable and
easy to handle Vilsmeier iminium type intermediate that has
been used for the formyl protection of primary hydroxyl groups
by Luca et al.[15] This reagent was also used for formylation
of enol ethers.[16] Another application of this reagent is in the
synthesis of alkyl chlorides and N-alkylphthalimides from alco-
hols.[17] The use of this reagent for the formylation of some
reactive aromatic compounds has also been reported.[18]
To obtain optimized conditions to convert aryl halides into
amides using TCT/DMF as amidating agent, iodobenzene was
selected as starting material. The obtained optimized condi-
tions are summarized in Table 1.
Comparison of the 13C NMR spectra shows that TCT was con-
sumed completely and that there is only DMF in the spectrum
of this salt. In the structure of TCT/DMF, the imminium carbon
signal appears at higher chemical shift (δ = 171.4 ppm) com-
pared with that of the DMF carbonyl group (δ = 167.3 ppm).
As shown in Table 1, a catalytic amount of Pd is needed
The peaks at δ = 160.6 and 155.1 ppm are attributed to carbon to accomplish the reaction with excellent isolated yield. In the
atoms of the TCT ring, which are deshielded by the iminium absence of phosphine ligand, at 140 °C, no product was ob-
group. According to the carbon chemical shifts, it can be sug- served by using PdCl2 as catalyst (entry 1), and for Pd(OAc)2 a
gested that the chemical structure B is more likely because the trace amount of the product was observed (entry 2). By use of
chemical shift of the C-atoms of the triazine ring are shielded PPh3 as ligand, 78 % of product was obtained after 2 h (entry 3).
by the negative charge on the O-atom in the iminium group. By changing the ligand to 1,1′-bis(diphenylphosphino)ferrocene
Comparison of the FTIR spectra of DMF, TCT, and TCT/DMF rea- (dppf), the reaction yield was enhanced to 91 % (entry 4). Other
gent, shown in Figure S1 (see the Supporting Information), ligands, dppp and dppe were also checked, but no increase in
clearly shows that the amidic C=O of DMF (1682 cm–1) disap- yield was observed (entries 5 and 6). The use of Pd/C catalytic
peared in the TCT/DMF reagent and two new peaks associated system was also studied but the reaction was did not reach
with the iminium bond appears at 1713 and 1612 cm–1. The completion (entry 7). Thus, the use of Pd(OAc)2/dppf catalyst
peaks corresponding to the TCT ring also disappeared and, in- system was selected as the best choice for this transformation.
Scheme 2. Three possible forms of DMF/TCT as amidating agent. Reaction conditions: TCT (1 mmol), DMF (0.5 mL), r.t., 1 h.
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Table 1. Optimization of the reaction conditions for the Pd-catalyzed amino-
carbonylation of iodobenzene by using the TCT/DMF reagent.[a]
Decreasing the amounts of Pd to 1.5 mol-% led to a significant
decrease in the yield of product (entry 9). When the optimum
amount of Pd was used in dioxane and toluene as solvent (en-
tries 8 and 9) the reaction yield was again decreased (entries 10
and 11). Furthermore, in the presence of K3PO4 as base, no
coupling product was detected; in this case, the TCT probably
reacts with base and no Vilsmeier iminium species is formed
(entry 12).
Entry
Catalyst (mol-%)
Temp.
[°C]
Time
[h]
Yield[b]
[%]
The required amount of TCT for this amidation reaction was
also studied and 1 mmol was selected as optimum. On the
basis of the obtained results, the best conditions for conversion
of aryl iodides into amides using aminocarbonylation with TCT/
DMF mixed reagent is that detailed in Table 1, entry 14.
1
2
3
4
5
6
7
8
PdCl2 (2.5)
Pd(OAc)2 (2.5)
140
140
120
120
120
120
120
120
120
120
120
120
120
120
140
24
24
5
2
2
2
2
2
2
2
2
2
2
2
24
0
trace
78
91
87
83
61
90
75
Pd(OAc)2(2.5)/PPh3 (10)
Pd(OAc)2(2.5)/dppf (5)
Pd(OAc)2(2.5)/dppp (5)
Pd(OAc)2(2.5)/dppe (5)
Pd/C (2.5)
Pd(OAc)2(2.0)/dppf (4)
Pd(OAc)2(1.5)/dppf (3)
Pd(OAc)2(2.0)/dppf (4)
Pd(OAc)2(2.0)/dppf (4)
Pd(OAc)2(2.0)/dppf (4)
Pd(OAc)2(2.0)/dppf (4)
Pd(OAc)2(2.0)/dppf (4)
PdCl2 (2.5)
Bromobenzene was also checked under the optimized condi-
tions and 84 % of product was observed after 6 h. Furthermore,
51 % of the desired product was obtained from the reaction of
chlorobenzene with TCT/DMF mixed reagent after 12 h. The
reaction yield was enhanced to 63 % when the temperature
was increased to 140 °C for chloroarene substrate.
9
10
11
12
13
14
15
65[c]
32[d]
0[e]
87[f]
90[g]
0
Having successfully applied TCT/DMF reagent for the amino-
carbonylation of iodobenzene, the scope of the reaction with
respect to the aryl halide was then explored (Scheme 3).
[a] Reaction conditions: TCT/DMF reagent preparation step: DMF (0.5 mL),
TCT (1 mmol), room temp., 2 h; coupling step: iodobenzene (1.0 mmol), DMF
(2.0 mL). [b] Isolated yield. [c] Dioxane was used as solvent. [d] Toluene was
used as solvent. [e] K3PO4 was used as base. [f] 0.8 mmol of TCT was used.
[g] 1.2 mmol iodobenzene was used.
Aryl halides having electron-donating (3b, 3c, and 3j) and
electron-withdrawing (3d–h) groups, were compatible under
the optimized conditions. Various functional groups, such as
methoxy (3b), methyl (3c), cyano (3e), and nitro (3d, 3f–h, and
3k) groups, were compatible with these conditions to give the
Scheme 3. Product of N,N-dimethylbenzamide with different aryl halides. Reaction conditions: 1. TCT (1 mmol) and DMF (0.5 mL), room temperature, 1 h;
2. aryl halide (1.2 mmol), Pd(OAc)2 (2.0 mol-%), dppf (4.0 mol-%), DMF (2 mL), 120–140 °C.
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desired products in good yields. All of the aryl halides investi-
gated produced the desired product, but the yield of reaction
for aryl chlorides were less, especially for unactivated rings.
Substrates with a methyl group in the ortho-position also pro-
ceeded smoothly to give 3j and 3k in good yields. Furthermore,
1-iodo- and 1-bromonaphthalene gave the corresponding
product (3l), in 90 and 81 % yield, respectively.
Encouraged by the above results, we turned our attention to
the use other formamides in the Pd-catalyzed aminocarbonyl-
ation of aryl halides. When N,N-diethylformamide was sub-
jected to the optimized reaction conditions, N,N-diethylbenz-
amides 4a–d were obtained in good to excellent yields
(Scheme 4).
Furthermore, to demonstrate the applicability of this meth-
odology in the synthesis of a diverse range of amides by using
other formamides, a selection of compounds was synthesized
Scheme 4. Product of N,N-diethylbenzamide with different aryl halides. Reac-
tion conditions: 1. TCT (1 mmol) and N,N-diethylformamide (0.5 mL), room
temperature, 1 h; 2. aryl halide (1.2 mmol), Pd(OAc)2 (2.0 mol-%), dppf
(4.0 mol-%), DMF (2 mL), 120–140 °C.
(Scheme 5). In this way, the formamide first reacted with TCT yields, respectively. The formyl-protected primary amines were
at 50 °C and the obtained salt was treated further under the also applicable in this methodology for amide synthesis, giving
optimized reaction conditions to obtain the desired amide 5f–i. By using this procedure, it was also possible to employ
product.
As shown in Scheme 5, it was also possible to synthesize
amide derivatives from different formamides. N,N-Diphenyl-
heterocyclic substrates under the optimized conditions, giving
the corresponding products 5j–l.
Overall, this synthetic methodology offers considerable im-
formamide gave good yield of the corresponding amide prod- provement over previous methods. For example, in this study,
uct 5a–c. N,N-Diisopropyl- and N,N-dibenzyl-formamides could expensive and corrosive reagents such as WCl6 and POCl3 were
also be used, with amides 5d and 5e being obtained in good replaced with TCT as an inexpensive, easily available and stable
Scheme 5. Synthesis of N,N-disubstituted benzamides under the optimized conditions. Reaction conditions: 1. TCT (1 mmol) and formamide (3.5 mmol), 50 °C,
1 h; 2. aryl halide (1.2 mmol), Pd(OAc)2 (2.0 mol-%), dppf (4.0 mol-%), DMF (2 mL), 120–140 °C.
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solutions with tetramethylsilane (TMS) as an internal standard. Fou-
rier-transform infrared (FTIR) spectroscopy with a Shimadzu FTIR-
8300 spectrophotometer was employed for characterization of
products. Melting points were determined in open capillary tubes
with a Barnstead electrothermal 9100 BZ circulating oil melting-
point apparatus. Reaction monitoring was accomplished with thin-
layer chromatography (TLC) on silica gel PolyGram SILG/UV254
plates. Column chromatography was carried out on columns of sil-
ica gel 60 (70–230 mesh).
reagent. In the previous methods, either a stoichiometric or an
excess amount of WCl6 and POCl3 were used, whereas in this
protocol less TCT is required to complete the reaction.
A reaction mechanism was also proposed according to previ-
ous reports (Scheme 6).[9a,9c]
General Procedure for the Amidation of Aryl Halides Using TCT/
DMF Reagent: Into a reaction tube, TCT (1 mmol, 0.189 g) and DMF
(0.5 mL or 3.5 mmol of non-liquid formamides) were added and the
mixture was stirred for 1–3 h at room temperature (or 50 °C). The
reaction mixture was then charged with aryl halide (1.2 mmol),
Pd(OAc)2 (2.0 mol-%), dppf (4.0 mol-%), DMF (2 mL) as solvent and
stirred for appropriate time specified in Schemes 3, 4, and 5 at
120–140 °C. Upon completion of the reaction (monitored by TLC),
a saturated solution of Na2CO3 (25 mL) was added to hydrolyze the
iminium salt for the formation of the amide group. Ethyl acetate
(25 mL) was added to the reaction mixture and the organic layer
was separated. The aqueous phases was extracted with ethyl acet-
ate (25 mL) and the combined organic layers were then dried with
anhydrous Na2SO4, filtered, and concentrated in vacuo to give the
crude product, which was purified by column chromatography (n-
hexane/ethyl acetate) to obtain the product with the desired purity.
N,N-Dimethylbenzamide (3a):[8] Yield 161 mg (90 %); m.p. 42–
43 °C. 1H NMR (250 MHz, CDCl3): δ = 2.95 (s, 3 H), 3.09 (s, 3 H), 7.38
(m, 5 H) ppm. 13C NMR (62.5 MHz, CDCl3): δ = 35.3, 39.5, 126.9,
128.3, 129.5, 136.3, 171.6 ppm. C9H11NO (149.19): calcd. C 72.46, H
7.43, N 9.39; found C 72.38, H 7.36, N 9.30.
Scheme 6. Proposed reaction mechanism.
Aryl halide can be oxidatively added to Pd0 to form complex
A. Reaction of the Vilsmeier iminium type intermediate with
complex A through Heck-type addition of aryl halides to the
iminium species resulted in the production of intermediate B.
Elimination of the palladium hydride species affords intermedi-
ate C, which, after hydrolysis, results in the formation of the
amide product. Removal of H from the Pd as HX regenerates
the Pd0 species, ready for the next cycle.
4-Methoxy-N,N-dimethylbenzamide (3b):[8] Yield 189 mg (88 %);
1
m.p. 195–197 °C. H NMR (250 MHz, CDCl3): δ = 3.05 (s, 6 H), 3.83
(s, 3 H), 6.89–6.92 (m, 2 H), 7.39–7.42 (m, 2 H) ppm. 13C NMR
(62.5 MHz, CDCl3): δ = 36.5, 39.7, 55.3, 113.5, 128.4, 129.1, 160.6,
171.5 ppm. C10H13NO2 (179.22): calcd. C 67.02, H 7.31, N 7.82; found
C 66.92, H 7.23, N 7.75.
N,N,4-Trimethylbenzamide (3c):[8] Yield 170 mg (87 %); m.p. 49–
51 °C. 1H NMR (250 MHz, CDCl3): δ = 2.37 (s, 3 H), 2.97 (s, 3 H), 3.07
(s, 3 H), 7.17–7.19 (m, 2 H), 7.30–7.33 (m, 2 H) ppm. 13C NMR
(62.5 MHz, CDCl3): δ = 29.6, 35.3, 39.6, 127.2, 128.9, 133.3, 139.6,
171.7 ppm. C10H13NO (163.22): calcd. C 73.59, H 8.03, N 8.58; found
C 73.52, H 7.94, N 8.51.
Conclusions
We have developed an efficient method for the Pd-catalyzed
aminocarbonylation of aryl halide by using the TCT/formamide
mixed reagent. The synthetic usefulness of this methodology
for amide synthesis was evaluated and a range of amide prod-
ucts were obtained in moderate to good yields in short reaction
times. The method is characterized by its simplicity, easy han-
dling of the reagents, and by the availability of the formylating
agent employed. The waste product formed from the TCT/
formamide reagent is cyanuric acid, which is safer and more
environmentally acceptable than the residue generated from
the Vilsmeier–Haack reagent.
N,N-Dimethyl-4-nitrobenzamide (3d):[9b] Yield 221 mg (95 %).
1H NMR (250 MHz, CDCl3): δ = 2.97 (s, 3 H), 3.15 (s, 3 H), 7.56–7.61
(m, 2 H), 8.25–8.30 (m, 2 H) ppm. 13C NMR (62.5 MHz, CDCl3): δ =
35.3, 39.3, 123.7, 128.0, 142.5, 148.2, 169.2 ppm. C9H10N2O3 (194.19):
calcd. C 55.67, H 5.19, N 14.43; found C 55.60, H 5.13, N 14.35.
4-Cyano-N,N-dimethylbenzamide (3e):[10a] Yield 194 mg (93 %);
1
m.p. 46–48 °C. H NMR (250 MHz, CDCl3): δ = 2.96 (s, 3 H), 3.13 (s,
3 H), 7.51–7.55 (m, 2 H), 7.70–7.75 (m, 2 H) ppm. 13C NMR (62.5 MHz,
CDCl3): δ = 35.3, 39.3, 113.3, 118.2, 127.7, 132.3, 140.7, 169.5 ppm.
C10H10N2O (174.20): calcd. C 68.95, H 5.79, N 16.08; found C 68.88,
H 5.71, N 16.00.
N,N-Dimethyl-2,4-dinitrobenzamide (3f):[10a] Yield 252 mg (88 %).
1H NMR (250 MHz, CDCl3): δ = 3.08 (s, 6 H), 7.04 (d, J = 9.7 Hz, 1 H),
8.19 (dd, J = 9.5, 2.7 Hz, 1 H), 8.70 (d, J = 2.7 Hz, 1 H) ppm. 13C NMR
(62.5 MHz, CDCl3): δ = 42.4, 116.7, 124.1, 127.7, 130.4, 136.2, 149.2,
170.0 ppm. C9H9N3O5 (239.19): calcd. C 45.19, H 3.79, N 17.57; found
C 45.09, H 3.71, N 17.48.
Experimental Section
General Experimental Details: Chemicals were purchased from
Merck and Aldrich chemical companies and used without further
purification. 1H NMR (250 MHz) and 13C NMR (62.9 MHz) spectra
were recorded with a Bruker Avance spectrometer in deuterated
chloroform (CDCl3) and deuterated dimethyl sulfoxide ([D6]DMSO)
N,N-Dimethyl-3,5-dinitrobenzamide (3g): Yield 243 mg (85 %).
1H NMR (250 MHz, CDCl3): δ = 2.72 (s, 3 H), 2.84 (s, 3 H), 8.64–8.67
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(m, 3 H) ppm. 13C NMR (62.5 MHz, CDCl3): δ = 34.9, 36.6, 120.7, 7.70–7.74 (m, 1 H), 8.00–8.29 (m, 3 H) ppm. 13C NMR (62.5 MHz,
128.6, 137.7, 148.0, 164.3 ppm. C9H9N3O5 (239.19): calcd. C 45.19, H
3.79, N 17.57; found C 45.11, H 3.73, N 17.50.
CDCl3): δ = 117.5, 120.5, 124.1, 127.1, 129.2, 129.4, 134.8, 137.7,
142.9, 147.5, 168.2 ppm. C19H14N2O3 (318.33): calcd. C 71.69, H 4.43,
N 8.80; found C 71.61, H 4.35, N 8.71.
4-Nitro-N,N-diphenylbenzamide (5b):[19] Yield 295 mg (80 %).
1H NMR (250 MHz, [D6]DMSO): δ = 7.30 (m, 10 H), 7.67–7.70 (m, 2
H), 8.07–8.10 (m, 2 H) ppm. 13C NMR (62.5 MHz, [D6]DMSO): δ =
123.0, 126.9, 127.7, 129.2, 129.6, 142.7, 142.8, 147.5, 167.8 ppm.
N,N-Dimethyl-3-nitrobenzamide (3h):[10a] Yield 191 mg (82 %).
1H NMR (250 MHz, CDCl3): δ = 2.89 (s, 3 H), 3.01 (s, 3 H), 7.51 (s, 1
H), 7.65 (s, 1 H), 8.14–8.21 (m, 2 H) ppm. 13C NMR (62.5 MHz, CDCl3):
δ = 35.5, 39.5, 122.2, 124.3, 129.7, 133.1, 137.6, 147.8, 168.9 ppm.
C9H10N2O3 (194.19): calcd. C 55.67, H 5.19, N 14.43; found C 55.58,
H 5.14, N 14.34.
C19H14N2O3 (318.33): calcd. C 71.69, H 4.43, N 8.80; found C 71.60,
H 4.36, N 8.72.
4-Chloro-N,N-dimethylbenzamide (3i):[10a] Yield 198 mg (90 %);
1
m.p. 57–59 °C. H NMR (250 MHz, [D6]DMSO): δ = 2.61 (s, 3 H), 2.69
3,5-Dinitro-N,N-diphenylbenzamide (5c): Yield 361 mg (83 %).
1H NMR (250 MHz, [D6]DMSO): δ = 6.50–6.56 (m, 2 H), 6.79–6.97 (m,
9 H), 8.60–8.67 (m, 2 H) ppm. 13C NMR (62.5 MHz, [D6]DMSO): δ =
116.5, 119.4, 119.8, 128.5, 128.9, 140.1, 143.3, 147.7, 164.7 ppm.
C19H13N3O5 (363.33): calcd. C 62.81, H 3.61, N 11.57; found C 62.73,
H 3.52, N 11.50.
(s, 3 H), 7.13–7.29 (m, 2 H), 7.67 (d, J = 8.5 Hz, 2 H) ppm. 13C NMR
(62.5 MHz, [D6]DMSO): δ = 34.7, 35.7, 128.2, 128.9, 133.9, 135.1,
168.9 ppm. C9H10ClNO (183.63): calcd. C 58.87, H 5.49, N 7.63; found
C 58.80, H 5.42, N 7.55.
N,N-2-Trimethylbenzamide (3j):[9c] Yield 164 mg (84 %). 1H NMR
(250 MHz, CDCl3): δ = 2.29 (s, 3 H), 2.84 (s, 3 H), 3.15 (s, 3 H), 7.18–
7.28 (m, 4 H) ppm. 13C NMR (62.5 MHz, CDCl3): δ = 18.9, 34.5, 38.4,
125.8, 125.9, 128.7, 130.3, 134.0, 136.7, 169.2 ppm. C10H13NO
(163.22): calcd. C 73.59, H 8.03, N 8.58; found C 73.52, H 7.97, N
8.49.
N,N-2-Trimethyl-4-nitrobenzamide (3k):[10a] Yield 219 mg (88 %).
1H NMR (250 MHz, CDCl3): δ = 2.33 (s, 3 H), 2.78 (s, 3 H), 3.07 (s, 3
H), 7.22–7.31 (m, 1 H), 7.99–8.03 (m, 2 H) ppm. 13C NMR (62.5 MHz,
CDCl3): δ = 19.0, 34.6, 38.1, 121.3, 125.2, 126.9, 136.3, 142.9, 147.8,
169.2 ppm. C10H12N2O3 (208.22): calcd. C 57.69, H 5.81, N 13.45;
found C 57.63, H 5.78, N 13.38.
N,N-Dimethyl-1-naphthamide (3l):[9c] Yield 215 mg (90 %).
1H NMR (250 MHz, CDCl3): δ = 2.81 (s, 3 H), 3.26 (s, 3 H), 7.43–7.53
(m, 4 H), 7.85–7.89 (m, 3 H) ppm. 13C NMR (62.5 MHz, CDCl3): δ =
34.8, 38.8, 123.8, 124.8, 125.2, 126.3, 126.9, 128.4, 129.0, 129.4, 133.4,
134.7, 170.9 ppm. C13H13NO (199.25): calcd. C 78.36, H 6.58, N 7.03;
found C 78.30, H 6.51, N 6.95.
N,N-Diethylbenzamide (4a):[9b] Yield 187 mg (88 %); m.p. 29–
31 °C. 1H NMR (250 MHz, CDCl3): δ = 1.10 (m, 3 H), 1.24 (m, 3 H),
3.25 (m, 2 H), 3.53 (m, 2 H), 7.36–7.38 (m, 5 H) ppm. 13C NMR
(62.5 MHz, CDCl3): δ = 12.7, 14.9, 36.6, 41.8, 126.2, 128.4, 129.1,
137.2, 171.3 ppm. C11H15NO (177.25): calcd. C 74.54, H 8.53, N 7.90;
found C 74.48, H 8.47, N 7.82.
N,N-Diethyl-4-methoxybenzamide (4b):[10a] Yield 211 mg (85 %).
1H NMR (250 MHz, CDCl3): δ = 1.19–1.20 (m, 6 H), 3.35–3.37 (m, 4
H), 3.83 (s, 3 H), 6.93–6.94 (m, 2 H), 7.33–7.34 (m, 2 H) ppm. 13C NMR
(62.5 MHz, CDCl3): δ = 12.7, 14.8, 36.6, 41.9, 55.3, 113.7, 128.2, 132.0,
162.3, 169.1 ppm. C12H17NO2 (207.27): calcd. C 69.54, H 8.27, N 6.76;
found C 69.48, H 8.22, N 6.69.
N,N-Diethyl-4-nitrobenzamide (4c):[10a] Yield 240 mg (90 %).
1H NMR (250 MHz, CDCl3): δ = 0.53–0.58 (m, 3 H), 0.65–0.70 (m, 3
H), 2.66–2.68 (m, 2 H), 2.98–3.00 (m, 2 H), 7.02 (d, J = 8.7 Hz, 2 H),
7.69 (d, J = 8.7 Hz, 2 H) ppm. 13C NMR (62.5 MHz, CDCl3): δ = 12.5,
13.8, 39.2, 43.0, 123.5, 127.1, 143.2, 147.6, 168.5 ppm. C11H14N2O3
(222.24): calcd. C 59.45, H 6.35, N 12.61; found C 59.37, H 6.29, N
12.55.
4-Chloro-N,N-diethylbenzamide (4d):[10a] Yield 211 mg (83 %).
1H NMR (250 MHz, CDCl3): δ = 1.13–1.19 (m, 6 H), 3.12–3.13 (m, 2
H), 3.37–3.39 (m, 2 H), 7.52–7.55 (m, 2 H), 7.90–7.93 (m, 2 H) ppm.
13C NMR (62.5 MHz, CDCl3): δ = 15.6, 45.9, 132.8, 133.2, 133.4, 134.3,
135.8, 142.5, 171.1 ppm. C11H14ClNO (211.69): calcd. C 62.41, H 6.67,
N 6.62; found C 62.34, H 6.61, N 6.55.
N,N-Diisopropyl-3,5-dinitrobenzamide (5d): Yield 287 mg (81 %).
1H NMR (250 MHz, [D6]DMSO): δ = 1.22 (s, 6 H), 1.24 (s, 6 H), 3.35
(s, 2 H), 8.85–8.90 (m, 3 H) ppm. 13C NMR (62.5 MHz, [D6]DMSO):
δ = 10.8, 16.4, 18.6, 46.0, 53.1, 120.6, 128.5, 137.9, 148.0, 164.2 ppm.
C13H17N3O5 (295.30): calcd. C 52.88, H 5.80, N 14.23; found C 52.81,
H 5.71, N 14.14.
N,N-Dibenzyl-4-nitrobenzamide (5e):[20] Yield 320 mg (77 %).
1H NMR (250 MHz, [D6]DMSO): δ = 4.33 (s, 2 H), 4.60 (s, 2 H), 7.10–
7.34 (m, 9 H), 7.69–7.72 (m, 2 H), 8.12–8.29 (m, 3 H) ppm. 13C NMR
(62.5 MHz, [D6]DMSO): δ = 47.0, 51.3, 123.6, 123.8, 126.8, 126.9,
127.3, 127.5, 127.6, 127.7, 128.6, 128.7, 130.6, 136.0, 136.3, 136.6,
142.3, 147.6, 149.9, 165.7, 169.4 ppm. C21H18N2O3 (346.39): calcd. C
72.82, H 5.24, N 8.09; found C 72.75, H 5.17, N 8.01.
N-(p-Tolyl)benzamide (5f):[10b] Yield 189 mg (75 %); m.p. 156–
158 °C. 1H NMR (250 MHz, [D6]DMSO): δ = 2.25 (s, 3 H), 7.11–7.15
(m, 2 H), 7.46–7.67 (m, 4 H), 7.91–7.95 (m, 2 H), 10.15 (s, 1 H) ppm.
13C NMR (62.5 MHz, [D6]DMSO): δ = 127.38, 127.42, 128.0, 128.1,
131.1, 134.0, 134.1, 168.1 ppm. C14H13NO (211.26): calcd. C 79.59, H
6.20, N 6.63; found C 79.48, H 6.11, N 6.55.
3-Nitro-N-(p-tolyl)benzamide (5g):[10b] Yield 218 mg (71 %).
1H NMR (250 MHz, [D6]DMSO): δ = 2.27 (s, 3 H), 7.17 (d, J = 8.2 Hz,
2 H), 7.62–7.84 (m, 4 H), 8.35–8.43 (m, 2 H), 8.75–8.77 (m, 1 H), 10.49
(s, 1 H) ppm. 13C NMR (62.5 MHz, [D6]DMSO): δ = 20.4, 120.4, 120.5,
122.3, 126.0, 129.0, 130.1, 133.1, 134.0, 147.7, 162.9 ppm.
C
14H12N2O3 (256.26): calcd. C 65.62, H 4.72, N 10.93; found C 65.55,
H 4.66, N 10.85.
N-(tert-Butyl)-4-nitrobenzamide (5h):[10b] Yield 186 mg (70 %).
1H NMR (250 MHz, [D6]DMSO): δ = 1.37 (s, 9 H), 7.96–8.02 (m, 2 H),
8.11 (s, 1 H), 8.22–8.27 (m, 2 H) ppm. 13C NMR (62.5 MHz,
[D6]DMSO): δ = 28.3, 123.2, 128.8, 141.5, 148.6, 164.6 ppm.
C11H14N2O3 (222.24): calcd. C 59.45, H 6.35, N 12.61; found C 59.38,
H 6.31, N 12.55.
N-Isopropyl-3-nitrobenzamide (5i):[10b] Yield 177 mg (71 %).
1H NMR (250 MHz, [D6]DMSO): δ = 1.13 (s, 3 H), 1.16 (s, 3 H), 4.04–
4.12 (m, 1 H), 7.66–7.72 (m, 1 H), 8.24–8.30 (m, 2 H), 8.59–8.64 (m,
2 H) ppm. 13C NMR (62.5 MHz, [D6]DMSO): δ = 22.0, 41.3, 121.8,
125.4, 129.7, 133.6, 136.0, 147.5, 163.0 ppm. C10H12N2O3 (208.22):
calcd. C 57.69, H 5.81, N 13.45; found C 57.69, H 5.81, N 13.45.
N,N-Dimethylnicotinamide (5j):[21] Yield 146 mg (81 %); m.p. 43–
45 °C. 1H NMR (250 MHz, CDCl3): δ = 2.91 (s, 3 H), 3.01 (s, 3 H),
7.34–7.39 (m, 1 H), 7.83 (d, J = 8 Hz, 1 H), 8.60 (d, J = 4.2 Hz, 1 H),
8.79 (s, 1 H) ppm. 13C NMR (62.5 MHz, CDCl3): δ = 37.6, 38.8, 126.4,
129.9, 132.3, 147.3, 148.3, 164.9 ppm. C8H10N2O (150.18): calcd. C
63.98, H 6.71, N 18.65; found C 63.90, H 6.66, N 18.58.
3-Nitro-N,N-diphenylbenzamide (5a): CAS No.: 73333-82-1. Yield
1
294 mg (77 %). H NMR (250 MHz, CDCl3): δ = 7.10–7.32 (m, 10 H),
Eur. J. Org. Chem. 2016, 1781–1787
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© 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
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1H NMR (250 MHz, [D6]DMSO): δ = 1.12 (s, 3 H), 1.20 (s, 3 H), 3.24
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Acknowledgments
Financial support from the research councils of Shiraz University
and a grant from the Iran National Elite Foundation are grate-
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Keywords: Synthetic methods · Palladium · Amides ·
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Received: December 26, 2015
Published Online: March 8, 2016
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