Pd/C-catalyzed aminocarbonylation of aryl iodides via oxidative C-N bond activation of tertiary amines to tertiary amides

Article abstract of DOI:10.1021/acs.joc.5b02385

This work reports oxidative N-dealkylation/carbonylation of tertiary amines to tertiary amides by using molecular oxygen as a sole oxidant using a Pd/C catalyst. This protocol is free from ligands, additives, bases, and cocatalysts. Different tertiary amines as well as aryl iodides have been examined for this transformation, providing desired products in good to excellent yield.

Full text of DOI:10.1021/acs.joc.5b02385

Note
pubs.acs.org/joc
Pd/C-Catalyzed Aminocarbonylation of Aryl Iodides via Oxidative
C−N Bond Activation of Tertiary Amines to Tertiary Amides
Rajendra S. Mane and Bhalchandra M. Bhanage*
Department of Chemistry, Institute of Chemical Technology, Mumbai 400019, India
S
* Supporting Information
ABSTRACT: This work reports oxidative N-dealkylation/carbonylation of tertiary amines to tertiary amides by using molecular
oxygen as a sole oxidant using a Pd/C catalyst. This protocol is free from ligands, additives, bases, and cocatalysts. Different
tertiary amines as well as aryl iodides have been examined for this transformation, providing desired products in good to excellent
yield.
In continuation of our ongoing work on Pd/C-catalyzed
carbonylation reactions,16 we describe herein a simple approach
for the direct synthesis of a wide range of tertiary amides under
mild conditions. Pd/C was found to be a highly efficient
catalyst for the carbonylation of aryl iodides via oxidative N-
dealkylation/carbonylation of tertiary amines using O2 as a sole
oxidant (Scheme 1).
Our studies began with the carbonylation of iodobenzene 1a
and triethyl amine 2a as an aminal source under the pressure of
CO/O2 (9:1) in MeCN using 10% Pd/C as a catalyst. Initially,
we examined various palladium precursors including PdCl2,
Pd(OAc)2, PdCl2(PPh3)2 with PPh3 as a ligand, and Pd/C
(Table 1). The results revealed that 10% Pd/C was the optimal
mide structural motifs are important functional groups
Abecause of their wide applications in pharmaceuticals,
natural products, agrochemicals, and biologically active
molecules.1,2 Traditionally, amides are synthesized by the
reaction of acyl chloride or carboxylic acid derivatives with
amines.3 Several named reactions, such as Beckmann,4
Staudinger,5 Ugi,6 and Ritter,7 are also known. Direct oxidative
amidation of aldehydes (or alcohols),8 hydroamination of
alkynes,9 and transamidation10 with amines are also widely
studied. Ours and other groups have disclosed DMF as a
coupling reagent for the synthesis of tertiary amides.11
However, despite their potential utility, these methods have
limitations due to their poor atom economy, the use of highly
hazardous reagents, and the expensive and toxic nature of many
of the coupling reagents.
Scheme 1. Overview of the Synthetic Approach for the
Tertiary Amides
The synthesis of secondary as well as tertiary amides through
carbonylation of aryl halides with primary and secondary
amines is studied.12 They have limitations due to the use of
excess base, additives, and moisture-sensitive phosphine ligands
along with non-recyclable Pd precursors. The C−N bond
activation of highly stable tertiary amine is a challenging task.13
The literature reveals that there are very few reports on the
carbonylation reactions.14 Recently, Deng et al. reported
carbonylative synthesis of amides via C−N bond activation of
tertiary amines.15 This protocol is disadvantageous as it requires
3.0 equiv of CuO as an oxidant for the cleavage of the C−N
bond as well as limits in their poor substrate scope and non-
recyclability with harsh reaction conditions. The use of Pd/C
catalysts has gained attention in green and sustainable
chemistry as it is inexpensive, easily available, and can be
recycled, thus making it an interesting catalytic system.
Molecular oxygen is considered as an ideal oxidant due to its
natural, inexpensive, and eco-friendly character.17
Received: October 14, 2015
© XXXX American Chemical Society
A
DOI: 10.1021/acs.joc.5b02385
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
Table 1. Summary of Screening of Catalyst, Loading of
Catalyst, and Ligands
Table 2. Screening of Optimized Reaction Parameters for
Aminocarbonylation Reactions
a
a
b
entry
solvent
temp (°C)
t (h)
PCO/O (bar)
yield (%)
b
2
entry
catalyst
PdCl2
mol %
L
yield (%)
1
MeCN
toluene
THF
100
100
100
100
120
90
8
8
10
10
10
10
10
10
10
10
10
10
10
7
95
79
65
58
93
83
74
94
95
84
61
94
95
92
63
0
1
2
3
4
5
6
7
8
9
5
5
5
5
5
5
5
3
7
3
PPh3
PPh3
PPh3
77
73
75
82
78
94
81
95
96
73
2
Pd(OAc)2
PdCl2(PPh3)2
PdCl2
3
8
4
DMF
8
5
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
8
Pd(OAc)2
10% Pd/C
5% Pd/C
10% Pd/C
10% Pd/C
10% Pd/C
6
8
7
80
8
8
100
100
100
100
100
100
100
100
100
100
24
12
6
9
10
11
12
13
14
c
10
4
a
Reaction conditions: 1a (1.0 mmol), Et3N (2.0 mmol), Pd catalyst,
Pd/P = 1/4, MeCN (10 mL) under 10 atm of CO/O2 (9:1) at 100 °C
for 8 h. GC and GCMS. With 2 equiv of CuO.
8
8
6
b
c
8
5
c
15
8
6
d
catalyst for this transformation (Table 1, entry 6). The Pd/C
catalyst works at a loading of 3 mol %, and 3a was obtained in
excellent yield (Table 1, entry 8). In the absence of Pd/C, the
reaction does not provide the desired product. It is noteworthy
that the reaction can also be performed in the presence of CuO
as an oxidant, regrettably, the yield of 3a decreased to 73%
(Table 1, entry 10).
16
8
6
e
17
8
6
95
a
Reaction conditions: 1a (1 mmol), 2a (2.0 mmol), 10% Pd/C (3 mol
%), solvent (10 mL) under CO atm, 1 atm of O2. GC and GCMS.
One atm of air. Under inert conditions, CO/O2 = 6/0 atm. Et3N
(1.5 mmol).
b
c
d
e
Scheme 2. Scope of Carbonylation of Aryl Iodides with
Triethyl Amine as Amine Source
Furthermore, we have investigated various reaction param-
eters for optimizing the yield of 3a, the results are summarized
in Table 2. First, we investigated the choice of solvent,
including acetonitrile, toluene, THF, and DMF. It was found
that the acetonitrile was the best solvent for this transformation,
which gave an excellent yield (Table 2, entry 1). When the
reaction temperature was lowered to 80 °C, the yield of 3a
decreased, whereas increasing it had no significant effect on the
yield of 3a (Table 2, entries 5−7). Conversely, when the
reaction time was reduced to 4 h, the yield of 3a was decreased
to 61%, and increasing the reaction time to 24 h had no
significant effect on yield (Table 2, entries 8−11). Under a 9:1
ratio of CO/O2 pressure, the reaction proceeded faster within 8
h to give 3a in 95% yield. We found that the corresponding
tertiary amide product was obtained in an excellent yield under
CO/O2 (5:1) pressure (Table 2, entry 13). When air was used
as the oxidant instead of O2, the obtained yield of 3a decreased
(Table 2, entry 15).18 In contrast, under an inert atmosphere,
the reaction did not proceed (Table 2, entry 16). Thus, this
indicates that molecular oxygen plays an important role in the
oxidative cleavage of tertiary amines to secondary amines.
Notably, the reaction was successfully performed with 1.5
mmol Et3N to afford 3a in 95% yield (Table 2, entry 17).
We examined the substrate scope of aryl iodides with Et3N
2a as an amine source, allowing the desired amides in high
yields at optimized reaction conditions (Scheme 2). Both
electron-rich and -deficient aryl iodides could be employed
efficiently under mild conditions (3a−3n). Aryl iodides bearing
methyl, methoxy, bromo, fluoro, nitro, and cyano substituents
on the phenyl ring were compatible with the developed
catalytic system, providing desired amides in good to excellent
yields. 1-Iodo and 2-iodonaphthalene were afforded excellent
yields of the corresponding amides (3f and 3g). Gratifyingly,
a
a
Reaction conditions: ArI (1.0 mmol), Et3N (1.5 mmol), Pd/C (3 mol
%), MeCN (10 mL) under 6 atm CO/O2 (5:1) at 100 °C for 8 h.
Isolated yield.
b
the double carbonylation of 1,4-diiodobenzene proceeded
smoothly and afforded desired amide 3n in 89% yield. The
phenyl tosylate and phenyl mesylate were also tested under the
optimized reaction conditions; unfortunately, the reaction did
not proceed. The carbonylation of heteroaryl iodides does not
B
DOI: 10.1021/acs.joc.5b02385
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The Journal of Organic Chemistry
Note
proceed, which could be because of the formation of stable
metal chelates with nitrogen of the heteroaryl iodides.
Scheme 4. Control Experiments
Subsequently, the scope of oxidative N-dealkylation/carbon-
ylation of a wide range of tertiary amines with 1a was also
investigated (Scheme 3). Both symmetrical as well as
Scheme 3. Scope of Carbonylation of Aryl Iodides with C−N
a
Bond Cleavage of Various Tertiary Amines
The recyclability of Pd/C catalyst was investigated by the
reaction of 1a with 2a under the optimal reaction conditions
(Table 3). The recovered catalyst could be reused up to five
Table 3. Reusability of Pd/C Catalyst
run
1st
95
2nd
94
3rd
92
4th
89
5th
88
b
yield (%)
a
Standard conditions: 1a (1 mmol), 2a (1.5 mmol), Pd/C (3 mol %),
b
CO/O2 = 5/1 in 10 mL of MeCN, 100 °C, 8 h. GC Yield.
times with a slight decrease in its catalytic activity. The leaching
of palladium metal was also explored and first and fifth recycle
samples subjected to the inductively coupled plasma atomic
emission spectrometry (ICP−AES) technique. No detectable
amount of palladium (below 0.1 ppm) was present in these
samples, indicating a negligible catalyst leaching.
a
Reaction conditions: 1a (1.0 mmol), amines (1.5 mmol), Pd/C (3
mol %), MeCN (10 mL), and 6 bar CO/O2 (5:1) at 100 °C for 8 h.
b
c
d
Isolated yield. With 5.0 mmol of 1a. With 2.0 equiv of CuO.
On the basis of experimental results and previous
literature,13d,f,g we proposed here a plausible reaction
mechanism for the palladium-catalyzed oxidative N-deal-
kylation/carbonylation of tertiary amines with aryl iodides
(Scheme 5). Initially, oxidative addition of ArI to Pd0 was
unsymmetrical tertiary amines reacted smoothly to afford the
corresponding amides in good yields. For symmetrical tertiary
amines, the selectivity of N-dealkylation independent of alkyl
chain lengths and oxidative N-dealkylation/carbonylation of
different aliphatic amines with 1a, afforded the corresponding
amides in high yields (3o and 3q−3u). In unsymmetrical
tertiary amines, N,N-diisopropylethyl amine, we observed three
kinds of N-dealkylation that potentially results in the formation
of three types of products (3pa, 3pb, and 3pc). N,N-
Dimethyloctyl amine also gave good yield selectively (3t).
Remarkably, trimethyl amine also proceeded smoothly and gave
the corresponding amides (3t). These results indicate that the
C−N bond cleavage of tertiary amines was selective at the less-
steric sides. When tribenzyl amines were used, the obtained
yield was very low (3u). For increasing the yield of 3u, the
reaction was carried out in the presence of 2 equiv of CuO,
which afforded 3u in 63% yield. When triphenyl amine (NPh3)
was used under the optimized conditions, the desired product
was not observed. In the case of cyclic tertiary amines, N-ethyl
and N-methyl derivatives of cyclic amines were also proven to
be good substrates (3v, 3w, and 3x). To further demonstrate
the robustness of developed catalytic system, we performed the
reaction on the gram scale under optimal reaction conditions. It
is noteworthy that the reaction of 5.0 mmol of 1a with Bu3N as
an amine source proceeded smoothly to give 3q in 86% yield.
Some control experiments were also carried out for the
confirmation of tertiary amines as an aminal source via C−N
bond activation. When HNEt2 was used as the amine source
under standard conditions, only 48% yield of 3a was obtained
(Scheme 4).
Scheme 5. Plausible Reaction Mechanism
followed by insertion of CO to form acylpalladium complex I.
The nitrogen of tertiary amines coordinates with complex I to
form complex II followed by elimination of HI to give a Pd-
imminium type intermediate (III).13f,g,19 Notably, the HI
liberated in situ are oxidized by oxygen to form water and
iodine.18 Furthermore, hydrolysis of III eliminates aldehyde
and forms complex IV. Finally, desired amide 3 was provided
by reductive elimination of complex IV with formation of Pd0
species and completion of the catalytic cycle.
C
DOI: 10.1021/acs.joc.5b02385
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The Journal of Organic Chemistry
Note
N,N-Diethyl-4-methoxybenzamide (3d).3i Colorless oil; 194.7 mg,
In summary, this work reports an efficient and novel Pd/C−
O2 catalytic system for the aminocarbonylation of aryl iodides
via C−N bond cleavage of tertiary amines as an amine source.
The present approach is simple to perform, scalable, recyclable,
ligand-free, additive-free, cocatalyst-free, and uses molecular
oxygen as an ideal and greener oxidant. Remarkably, a wide
range of substrates of aryl iodides as well as tertiary amines are
well-tolerated.
1
94% yield. H NMR (400 MHz, CDCl3): δ 7.27 (d, J = 8.3 Hz, 2H),
6.83 (d, J = 8.4 Hz, 2H), 3.75 (s, 3H), 3.31 (s, 4H), 1.11 (s, 6H). 13C
NMR (101 MHz, CDCl3): δ 171.2, 160.2, 129.3, 128.1, 113.6, 55.2,
43.3, 39.3, 14.1, 9.3. GC-MS (EI, 70 eV) m/z (%): 207 (13) [M]+, 206
(29.5), 135 (100), 107 (13), 92 (14), 77 (21), 42 (3.5).
N,N-Diethyl-2-methoxybenzamide (3e).3i Colorless oil; 163.6 mg,
1
79% yield. H NMR (500 MHz, CDCl3): δ 7.29 (dd, J = 8.3, 7.5 Hz,
1H), 7.16 (d, J = 7.4 Hz, 1H), 6.95−6.87 (m, 2H), 3.78 (s, 3H), 3.57−
3.51 (m, 2H), 3.14−3.10 (q, 2H), 1.22 (t, 3H), 1.00 (t, 3H). 13C NMR
(126 MHz, CDCl3): δ 168.8, 155.1, 129.9, 127.4, 126.8, 120.7, 110.9,
55.46, 42.8, 38.8, 13.9, 12.9. GC-MS (EI, 70 eV) m/z (%): 207 (9)
[M]+, 206 (29), 135 (100), 92 (11), 77 (23), 42 (3).
EXPERIMENTAL SECTION
■
General. The Pd/C was purchased from Sigma-Aldrich (10 wt %
loading; matrix: activated carbon support; product number: 205699;
brand: Aldrich). Solvents were purchased with high purity and used
without further purification. All of the reactions were monitored by
using TLC, GC, and GC-MS techniques. Products were purified by
N,N-Diethyl-1-naphthamide (3f).12i Colorless oil; 220.3 mg, 97%
yield. 1H NMR (400 MHz, CDCl3): δ 7.93−7.69 (m, 2H), 7.54−7.44
(m, 2H), 7.39 (dd, 1H), 3.82 (s, 1H), 3.50 (s, 1H), 3.00−3.04 (t, 1H),
1.34 (t, 3H), 0.95 (t, 3H). 13C NMR (101 MHz, CDCl3): δ 170.3,
135.1, 133.4, 129.5, 128.7, 128.3, 126.8, 126.3, 125.1, 124.7, 123.1,
43.1, 39.0, 14.2, 13.0. GC-MS (EI, 70 eV) m/z (%): 227 (38) [M]+,
226 (44), 198 (3), 155 (100), 127 (84), 101 (5), 77 (8), 51(2).
N,N-Diethyl-2-naphthamide (3g).8e Colorless oil; 222.5 mg, 98%
yield. 1H NMR (400 MHz, CDCl3): δ 7.84 (t, J = 6.4 Hz, 4H), 7.55−
7.41 (m, 3H), 3.58 (s, 2H), 3.29 (s, 2H), 1.26 (s, 3H), 1.11 (s, 3H).
13C NMR (101 MHz, CDCl3): δ 171.4, 134.4, 133.3, 132.7, 128.3,
128.2, 127.7, 126.7, 126.6, 125.7, 123.8, 43.4, 39.4, 14.2, 12.9. GC-MS
(EI, 70 eV) m/z (%): 227 (29) [M]+, 226 (41), 198 (2), 155 (100),
127 (71), 101 (5), 77(6), 51(2).
1
column chromatography on silica (100−200 mesh). The H NMR
spectra were recorded on a 400 and 500 MHz spectrometer in CDCl3
using tetramethylsilane (TMS) as the internal standard. The 13C NMR
spectra were recorded on a 101 and 126 MHz spectrometer in CDCl3.
Chemical shifts are reported in parts per million (δ) relative to TMS as
the internal standard. The J (coupling constant) values are described in
Hz. Splitting patterns of proton are depicted as s (singlet), d
(doublet), t (triplet), and m (multiplet). The products were confirmed
by the comparison of their GC-MS and 1H and 13C NMR spectra with
those of authentic data.
General Experimental Procedure for Oxidative N-Deal-
kylation/Carbonylation of Tertiary Amines with Aryl Iodides.
To a 100 mL stainless steel autoclave were added aryl iodide (1
mmol), tertiary amine (1.5 mmol), and 10% Pd/C (3 mol %) in 10
mL of MeCN. The autoclave was closed and pressurized with oxygen
(1 atm) and CO (5 atm) without flushing. The reaction mixture was
stirred with a mechanical stirrer (550 rpm) and heated at 100 °C for 8
h. The reactor was then cooled to room temperature and degassed
carefully, and the reactor was opened. The reactor vessel was washed
with ethyl acetate (3 × 5 mL) to remove traces of product and catalyst
if present. The reaction mixture was filtered; filtrates were dried over
Na2SO4, and the solvent was evaporated under vacuum. Products were
purified using column chromatography (Silica gel 100−200 mesh,
petroleum ether/ethyl acetate) to afford the corresponding products in
good to excellent yields. The purities of compounds were confirmed
by GC and GCMS analysis. The structures of products were confirmed
by GC-MS and 1H and 13C NMR spectroscopic techniques (Caution!
CO and O2 may form an explosive mixture under certain conditions).19
Procedure for Recycling of Catalyst. After completion of the
reaction, the recovered catalyst was washed with distilled water (3 × 5
mL) and finally with methanol (3 × 5 mL) to remove trace amounts of
organic material. Then, the catalyst was dried in an oven at 80 °C for 5
h and after washing and drying, and the catalyst was reused for the
next run.
4-Cyano-N,N-diethylbenzamide (3h).3i White solid; 196 mg, 97%
1
yield. H NMR (400 MHz, CDCl3): δ 7.67 (d, J = 8.0 Hz, 2H), 7.44
(d, J = 8.0, 2 Hz, 2H), 3.51 (d, J = 6.6 Hz, 2H), 3.16 (d, J = 6.7 Hz,
2H), 1.15 (dd, J = 56.9, 6.4 Hz, 6H). 13C NMR (101 MHz, CDCl3): δ
169.1, 141.5, 132.3, 127.0, 118.2, 112.9, 43.2, 39.4, 14.8, 12.8. GC-MS
(EI, 70 eV) m/z (%): 202 (10) [M]+, 201 (27), 159 (3), 130 (100),
102 (37), 75 (8), 51(6).
4-Bromo-N,N-diethylbenzamide (3i).8g Colorless oil; 227 mg, 89%
yield. 1H NMR (400 MHz, CDCl3): δ 7.52−7.44 (m, 2H), 7.23−7.17
(m, 2H), 3.47 (s, 2H), 3.18 (s, 2H), 1.18 (s, 3H), 1.05 (s, 3H). 13C
NMR (101 MHz, CDCl3): δ 170.2, 135.9, 131.6, 128.0, 123.3, 43.3,
39.3, 14.2, 12.8. GC-MS (EI, 70 eV) m/z (%): 255 (62) [M]+, 254
(62), 184 (90), 182 (100), 156 (30), 154 (31.3), 104 (18.4), 76 (39),
75 (27), 50 (16.5), 42 (16.5).
4-Fluoro-N,N-diethyl-benzamide (3j).3j Colorless oil; 169.7 mg,
1
87% yield. H NMR (400 MHz, CDCl3): δ 7.47−7.09 (dd, 2H), 7.02
(dd, 2H), 3.47 (s, 2H), 3.20 (s, 2H), 1.12 (d, 6H). 13C NMR (101
MHz, CDCl3): δ 170.3, 164.2, 161.7, 133.2, 133.2, 128.4, 128.4, 115.5,
115.3, 43.3, 39.4, 14.1, 12.8. GC-MS (EI, 70 eV) m/z (%): 195 (10.5)
[M]+, 194 (28), 166 (2), 123 (100), 95 (33), 75 (10), 42 (10).
N,N-Diethyl-4-nitrobenzamide (3k).3i Yellow oil; 219.9 mg, 99%
1
yield. H NMR (400 MHz, CDCl3): δ 8.43−8.12 (d, 2H), 7.58−7.34
(d, 2H), 3.51 (s, 2H), 3.15 (q, 2H), 1.13 (t, 6H). 13C NMR (101
MHz, CDCl3): δ 168.9, 147.9, 143.3, 127.3, 123.8, 43.2, 39.4, 14.1,
12.8. GC-MS (EI, 70 eV) m/z (%): 222 (16) [M]+, 221 (36.5), 205
(7), 175 (5), 150 (100), 120 (14), 134 (34.5), 92 (14.2), 76 (26), 32
(17).
N,N-Diethylbenzamide (3a).8h Colorless oil; 168.2 mg, 95% yield.
1H NMR (400 MHz, CDCl3): δ 7.31 (m, 5H), 3.48 (s, 2H), 3.19 (s,
2H), 1.18 (s, 3H), 1.04 (s, 3H). 13C NMR (101 MHz, CDCl3): δ
171.3, 137.1, 129.0, 128.3, 126.2, 43.2, 39.2, 14.1, 12.8. GC-MS (EI, 70
eV) m/z (%): 177 (12) [M]+, 176 (33), 148 (4), 134 (3), 105 (100),
77 (52), 51 (17).
N,N-Diethyl-3-nitrobenzamide (3l).3i Yellow oil; 215.4 mg, 97%
yield. 1H NMR (400 MHz, CDCl3): δ 8.43−7.94 (m, 2H), 7.68 (dd, J
= 7.6, 1H), 7.57 (dd, 1H), 3.53 (d, 2H), 3.21 (d, 2H), 1.23 (s, 3H),
1.10 (s, 3H). 13C NMR (101 MHz, CDCl3): δ 168.6, 147.9, 138.6,
132.4, 129.7, 124.0, 121.5, 43.4, 39.6, 14.2, 12.9. GC-MS (EI, 70 eV)
m/z (%): 222 (10) [M]+, 221 (20), 204 (9), 150 (100), 134 (5.4), 104
(32), 76 (24.8), 50 (5).
N,N-Diethyl-4-methylbenzamide (3b).12g Colorless oil; 183.4 mg,
96% yield. 1H NMR (400 MHz, CDCl3): δ 7.25−7.20 (dd, 8 Hz, 2H),
7.14 (dd, J = 7.9 Hz, 2H), 3.49 (s, 2H), 3.22 (s, 2H), 2.32 (s, 3H), 1.18
(s, 3H), 1.07 (s, 3H). 13C NMR (101 MHz, CDCl3): δ 171.5, 139.0,
134.2, 128.9, 126.2, 43.2, 39.2, 21.3, 14.1, 12.8. GC-MS (EI, 70 eV) m/
z (%): 191 (14) [M]+, 190 (36), 162 (3), 148 (2.5), 119 (100), 91
(41), 65 (19.5), 42 (4.5).
N,N-Diethyl-2-nitrobenzamide (3m). Yellow oil; 179.9 mg, 81%
1
N,N-Diethyl-2-methylbenzamide (3c).12g Colorless oil; 156.7 mg,
yield. H NMR (400 MHz, CDCl3): δ 8.15 (d, J = 8.2 Hz, 1H), 7.66
1
(td, J = 7.5, 1H), 7.51 (td, J = 8.3, 1H), 7.38−7.32 (m, 1H), 3.55 (s,
2H), 3.08 (q, 2H), 1.27−1.20 (m, 3H), 1.04−0.98 (m, 3H). 13C NMR
(101 MHz, CDCl3): δ 167.2, 144.9, 134.3, 133.5, 129.5, 127.9, 124.7,
42.7, 38.9, 13.5, 11.9. GC-MS (EI, 70 eV) m/z (%): 222 (2) [M]+, 161
(3), 151 (72), 150 (79), 134 (12.5), 121 (18.5), 104 (15), 72 (100),
51 (33.6), 44 (13), 39 (55).
82% yield. H NMR (400 MHz, CDCl3): δ 7.70−6.62 (m, 4H), 3.52
(d, 2H), 3.06 (d, 2H), 2.23 (s, 3H), 1.21 (t, 3H), 0.97 (t, 3H). 13C
NMR (101 MHz, CDCl3): δ 170.8, 137.0, 133.7, 130.2, 128.4, 125.7,
125.3, 42.5, 38.6, 18.7, 13.9, 12.8. GC-MS (EI, 70 eV) m/z (%): 227
(29) [M]+, 226 (41), 198 (2), 155 (100), 127 (71), 101 (5), 77(6),
51(2).
D
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The Journal of Organic Chemistry
Note
N1,N1,N4,N4-Tetraethylterephthalamide (3n).3h White solid; 245.8
m/z (%): 191 [M+] (9), 190 (24.68), 176 (7), 105 (100), 84(10), 77
(42.31), 56 (12).
1
mg, 89% yield. H NMR (400 MHz, CDCl3): δ 7.35 (s, 4H), 3.50 (s,
4H), 3.19 (s, 4H), 1.20−1.04 (m, 12H). 13C NMR (101 MHz,
CDCl3): δ 170.6, 137.9, 126.4, 43.2, 39.2, 14.2, 12.8. GC-MS (EI, 70
eV) m/z (%): 276 (33) [M]+, 275 (56), 247 (10), 233 (2), 205 (21),
204 (100), 176 (7), 132 (8), 105 (28), 105 (28), 76 (12), 44 (5).
N,N-Dipropylbenzamide (3o).12g Colorless oil; 190.8 mg, 93%
Phenyl(pyrrolidin-1-yl)methanone (3x).8i Colorless oil; 85.7 mg,
49% yield. 1H NMR (400 MHz, CDCl3): δ 7.52−7.41 (m, 2H), 7.41−
7.37 (m, 3H), 3.64 (t, 2H), 3.42 (t, 2H), 2.04−1.93 (p, 2H), 1.90−
1.83 (p, 2H). 13C NMR (101 MHz, CDCl3): δ 169.7, 137.1, 129.8,
128.2, 127.0, 77.4, 77.1, 76.8, 49.6, 46.8, 26.3, 24.4. GC-MS (EI, 70
eV) m/z (%): 175 [M+] (30), 146 (13), 122 (8), 105 (100), 77 (72),
51 (25), 32 (10).
1
yield. H NMR (400 MHz, CDCl3): δ 7.34−7.28 (m, 5H), 3.41 (s,
2H), 3.11 (s, 2H), 1.65 (d, J = 6.8 Hz, 2H), 1.47 (d, J = 6.7 Hz, 2H),
0.95−0.69 (m, 6H). 13C NMR (101 MHz, CDCl3): δ 171.7, 137.3,
128.9, 128.3, 126.3, 50.6, 46.2, 21.8, 20.6, 11.4, 11.0. GC-MS (EI, 70
eV) m/z (%): 205(10) [M]+, 204 (14), 176 (7), 134 (8), 105 (100),
77 (35), 51 (7).
ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.joc.5b02385.
■
S
N,N-Diisopropylbenzamide (3pa).12g White solid; 49.2 mg, 24%
1
yield. H NMR (400 MHz, CDCl3): δ 7.34−7.24 (m, 5H), 3.80 (s,
1H), 3.49 (s, 1H), 1.50−1.11 (m, 12H). 13C NMR (101 MHz,
CDCl3): δ 171.1, 138.8, 132.6, 129.8, 128.6, 128.4, 128.1, 125.5, 50.9,
45.8, 20.7. GC-MS (EI, 70 eV) m/z (%): 205 (3) [M]+, 190 (7), 162
(11), 105 (100), 77 (32.5), 51(8), 40 (27.8).
1H and 13C NMR spectra and analysis by GC-MS (PDF)
AUTHOR INFORMATION
Corresponding Author
*Tel: +91 22 33612603. Fax: +91 22 33611020. E-mail: bm.
bhanage@ictmumbai.edu.in.
■
N-Ethyl-N-isopropylbenzamide (3pb). GC-MS (EI, 70 eV) m/z
(%): 191 (3) [M]+, 190 (5), 163 (10), 162 (8), 148 (7), 122 (5), 105
(100), 77 (43), 51(15), 32 (29).
N-Isopropylbenzamide (3pc).8f White solid; 63.6 mg, 39% yield.
1H NMR (400 MHz, CDCl3): δ 7.74−7.71 (m, 2H), 7.46−7.37 (m,
3H), 5.97 (s, 1H), 4.26 (m, 1H), 1.24 (s, 6H). 13C NMR (101 MHz,
CDCl3): δ 166.7, 13.9, 131.2, 130.0, 128.5, 128.3, 126.8, 41.9, 22.8.
GC-MS (EI, 70 eV) m/z (%): 163 (23) [M]+, 162 (8.5), 148 (10),
106 (8), 105 (100), 77 (35), 51 (11).
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
R.S.M. gratefully acknowledges the Council of Scientific &
Industrial Research (CSIR), New Delhi, India for a Senior
Research Fellowship (SRF) award.
N,N-Dibutylbenzamide (3q).15 Colorless oil; 200.5 mg, 93% yield.
1H NMR (400 MHz, CDCl3): δ 7.35−7.24 (m, 5H), 3.42 (q, 2H),
3.15 (q, 2H), 1.44−1.36 (m, 4H), 1.22−1.09 (m, 2H), 0.94−0−0.74
(m, 6H). 13C NMR (101 MHz, CDCl3): δ 171.7, 137.2, 129.88, 129.0,
128.3, 128.2, 126.4, 48.7, 44.4, 30.7, 29.6, 20.2, 19.7, 13.9, 13.5. GC-
MS (EI, 70 eV) m/z (%): 233 (8) [M]+, 232 (7), 190 (12), 148 (5),
134 (4), 105 (100), 77 (25.9), 51(4), 40 (11).
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■
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1
and 83% yield. H NMR (500 MHz, CDCl3): δ 7.43−7.26 (m, 5H),
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1
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1
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