A novel method for the conversion of carboxylic acids to N,N-dimethylamides using N,N-dimethylacetamide as a dimethylamine source

Article abstract of DOI:10.3184/174751913X13602686612047

A simple, cost effective and environmentally benign method is reported for the preparation of N,N-dimethylamides from carboxylic acids. The versatility of the method is determined by synthesising a large number of N,N-dimethylamide derivatives. Carboxylic acids are heated at 160-165°C in N,N-dimethylacetamide solvent in the presence of1,1'-carbonyldiimidazole to afford the corresponding N,N-dimethylamides in good to excellent yields.

Full text of DOI:10.3184/174751913X13602686612047

JOURNAL OF CHEMICAL RESEARCH 2013
RESEARCH PAPER 155
MARCH, 155–159
A novel method for the conversion of carboxylic acids to N,N-dimethyl-
amides using N,N-dimethylacetamide as a dimethylamine source
Sanjeev Kumar Aavula*, Anil Chikkulapally, N. Hanumanthappa, Indira Jyothi, C.H. Vinod
Kumar, Sulur G. Manjunatha, and Suresh Kumar Sythana
Pharmaceutical Development, AstraZeneca India Pvt. Ltd, off Bellary Road, Hebbal, Bangalore 560 024, India
A simple, cost effective and environmentally benign method is reported for the preparation of N,N-dimethylamides
from carboxylic acids. The versatility of the method is determined by synthesising a large number of N,N-dimethyl-
amide derivatives. Carboxylic acids are heated at 160–165 °C in N,N-dimethylacetamide solvent in the presence of
1,1′-carbonyldiimidazole to afford the corresponding N,N-dimethylamides in good to excellent yields.
Keywords: N,N-dimethylacetamide, 1,1′-carbonyldiimidazole, carboxylic acids, amidation, one-pot synthesis
In general, synthetic methods for N,N-dimethylamides require
the reaction of acid chlorides with N,N-dimethylamines in the
presence of activating agents. The most typical and industri-
ally used method for the preparation of N,N-dimethylbenza-
mide is the heating of commercially available benzoyl chloride
at 150 °C in dimethylformamide (DMF) for a long time.1 A
mixture of DMF and thionyl chloride is known to generate a
Vilsmeier complex at 80 °C, and this complex acts as a reagent
for chlorination of benzoic acids2 followed by a N,N-dimethyl-
amino group transfer reaction between benzoyl chlorides and
DMF at 150 °C. An alternative method for the synthesis of
N,N-dimethylamides is to use carboxylic acids and dimethyl
amine in the presence of coupling reagents.3 Tetrakis(dimethy
lamino)silane in an anhydrous solvent at high temperature has
been used for the preparation of N,N-dimethylamides from
carboxylic acids.4 A one-pot tandem chlorination and amida-
tion reaction of carboxylic acids in DMF in the presence of
thionyl chloride at 150 °C has been reported by Kumagai
et al.5 Kaboudin and Haghighat reported a one-pot conversion
of carboxylic acids into N,N-dimethylamides by using N,N-
dimethylsulfamoyl imidazole/N,N-dimethylsulfamoyl chloride
in the presence of a mixture of methanesulfonic acid and
phosphorus pentoxide.6 Recently, Xavier et al. Reported
solvent-free formation of amide bonds from carboxylic acids
and amines using 1,1′-carbonyldiimidazole (CDI).7
A few direct methods of N,N-dimethylamination of acid
chlorides with DMF solvent1,2 at 150 °C for longer time have
been reported in the literature. These processes involve the
formation of a Vilsmeier complex (N,N-dimethylchloromethy-
liminium chloride) which is known to be explosive under
certain conditions, for example, in contact with metals, and
may also undergo decomposition to produce sulfur, dimethyl-
carbamoylchloride (a potent animal carcinogen) and liberation
of toxic gases like sulfur dioxide (from thionyl chloride) and
carbon monoxide (from the DMF solvent).
We report here a safe, efficient and novel method for
the N,N-dimethylamination of carboxylic acids (Scheme 1).
Carboxylic acids were heated at 160–165 °C in N,N-dimethyl-
acetamide solvent in the presence of CDI to afford the corre-
sponding N,N-dimethylamides in good to excellent yields in
short times. To the best of our knowledge, there is no report in
the literature that DMAc solvent in combination with CDI can
be used as a source of N,N-dimethylamine. The advantages
of this method are that the by-products are carbon dioxide,
N-acetyl imidazole and imidazole which are not especially
hazardous; in addition to this the imidazole and N-acetyl imid-
azole by-products can be washed out by simple water washes.
Results and discussion
We wished to synthesise benzamide 3, which we planned to do
by coupling of acid 1 and aniline 2 with CDI mediated amide
coupling in dimethylacetamide (DMAc) solvent at 55–60 °C
for 120 mins (Scheme 2), but were surprised to find 4 (15–20%
area by HPLC) along with product 3. This finding encouraged
us to study the scope and limitations of DMAc as a potential
Scheme 1 Synthesis of N,N-dimethylamides where FG=CN,
N(CH3)2, F, Br, Me, CH=CH2, COCH3, COOH, OMe.
Scheme 2 CDI-mediated amidation in DMAc solvent.
* Correspondent. E-mail: Sanjeev.aavula@astrazeneca.com

156 JOURNAL OF CHEMICAL RESEARCH 2013
Table 1 Amidation of imidazolide 6 under different reaction
conditions
N,N-dimethyl amine precursor for amidation reaction in more
detail.
First, we attempted to synthesise N,N-dimethylbenzamide 7
from benzoic acid 5 in DMAc solvent without an external
amine source to assess whether one pot N,N-dimethylamina-
tion is accessible in the presence of the CDI reagent. Thus,
benzoic acid (1.0 g, 0.0081 mol) and CDI (2.0 g, 0.012 mol)
were heated to 160–165 °C in dry N,N-dimethylacetamide
(10 mL) solvent. The benzamide 7 could be isolated in 82%
yield after a reaction time of 1 h (Scheme 3).
Entry Substrate DMAc CDI/mol Imidazole Time Purity by
/mL
equiv. /mol equiv. /h HPLC 7/%
1
2
3
4
6
6
6
6
10
10
10
10
1.0
0.25
–
–
–
1.0
–
2.0
4.0
24.0
6.0
85
84
66
0
–
Reactionconditions:imidazolide6(0.05moles), CDI(0.05/0.0015
moles), imidazole (0.05 moles), and heating (160–165 °C, 2–24 h).
To investigate the mechanism of the reaction a series of
experiments were screened with isolated imidazolide interme-
diate 6 (N-benzoylimidazole), and the results are presented in
Table 1. The amidation reaction proceeded smoothly in the
presence of CDI/imidazole (entries 1–3). The reaction is much
faster with CDI reagent as compared to imidazole. Attempts to
conduct the amidation reaction only with DMAc solvent in the
absence of both CDI and imidazole (entry 4), did not produce
amidation product 7 and the starting material was recovered
almost quantitatively by column chromatography.
corresponding to mass 110 and 149 were observed, which
corresponded to the structures of N,N-Dimethylbenzamide (7)
and N-acetyl imidazole respectively (Figs 1, 2 and 3).
Based on the above optimisation work (Table 1) and GC-MS
analysis, the reaction mechanism (Scheme 4) for the formation
of N,N-dimethylamides may be suggested; nucleophilic attack
of imidazole on DMAc results in the formation of tetrahedral
intermediate A. Attack on the tetrahedral intermediate by
imidazole leads to the generation of N-acetyl imidazole and
N,N-dimethylamine. So it is then possible that the liberated
A reaction sample was withdrawn for gas chromatography
mass spectrometric analysis (GCMS) after 1 h. Two peaks
Scheme 3 N,N-Dimethylamination of benzoic acid.
Fig. 1 GC trace of N,N-dimethylamination of benzoic acid.
Fig. 2 GC-MS of N-acetyl imidazole.

JOURNAL OF CHEMICAL RESEARCH 2013 157
Fig. 3 GC-MS of N,N-dimethylbenzamide (7).
dimethylamine reacts with the reactive species imidazolide to
yield the amide.
the multiple spots in TLC. The amination reaction of a disub-
stituted acid substrate (Table 2, entry 14) was examined under
the conditions. The yield of phthalamide was relatively low
(< 10%) probably due to poor solubility of the acids in DMAc.
When the reaction times were prolonged, the yields went up to
80%. Due to poor solubility of the product in isopropyl acetate
solvent, this was replaced by the highly polar solvent n-butanol
for extraction of the product. The reaction even worked well
for five membered heterocycles. For example, 2-furonoic acid
gave N,N-dimethylfuran-2-carboxamide (Table 2, entry 8)
in 64% yield. Amination of 1-naphthalenecarboxylic acid
(Table 2, entry 10) successfully produced N,N-dimethyl-1-
naphthamide in good yield. The reaction equally worked for
the aliphatic acids (Table 2, entries 13, 18 and 19) that were
examined under the conditions.Amination proceeded smoothly
to afford corresponding N,N-dimethylamide products in
70–76% yields.
The dimethylamination of benzoic acid (Table 2, entry 12)
using DMAc and CDI was the first N,N-dimethylamination
reaction to be investigated. Benzoic acid was added to 2.0
equiv. of CDI in DMAc solvent and heated at 160–165 °C for
1.5 h. HPLC analysis of the crude reaction product showed
that the reaction had proceeded to 100% conversion. The reac-
tion mixture could be readily purified by extracting the product
in isopropyl acetate solvent followed by water washes to
remove the by-products. The solvent was then concentrated
under reduced pressure to give an analytically pure sample
of N,N-dimethylbenzamide (Table 2, entry 12) in 82% yield
without the need for column chromatography. This successful
dimethylamination protocol was then applied to a range of
carboxylic acids, with the results summarised in Table 2.
The dimethylamination reactions of benzoic acid derivatives
(Table 2, entries 1–7, 9, 10, 12, 15 and 16) proceeded well,
enabling the N,N-dimethylamides products to be isolated
above 80% yields, except for 4-formylbenzoic acid where
product formation was observed. Here decomposition had
occurred under the conditions for proposed 4-formyl-N,N-
dimethylbenzamide preparation (Table 2, entry 17) leading to
Conclusions
In conclusion, DMAc in combination with CDI provides a
simple, mild, good yield and relatively clean reaction for the
synthesis of N,N-dimethylamides. This method is an attractive
Scheme 4 A proposed mechanism of N,N-dimethylamination of carboxylic acid.

158 JOURNAL OF CHEMICAL RESEARCH 2013
Table2 ConversionofcarboxylicacidstoN,N-dimethylamides
using DMAc and CDI at 160–165 °C
products gave satisfactory analytical data. Identification of the prod-
1
ucts was carried out by H NMR, 13C NMR and mass spectroscopic
analytical techniques.
N,N-Dimethyl-4-cyanobenzamide (9a):5 Yield (85%); colourless
solid: m.p. 98–100 °C (lit.5 99–100 °C); 1H NMR (400 MHz, CDCl3):
δ 7.76–7.67 (d, J = 8.5 Hz, 2H), 7.57–7.49 (d, J = 8.5 Hz, 2H), 3.13
(s, 3H), 2.96 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 169.3, 140.6,
132.2, 127.5, 118.1, 113.0, 39.2, 35.1.
Entry
R
Product Time/h Yield/%a
N,N-Dimethyl-4-dimethylaminobenzamide (9b):5 Yield (80%);
1
2
p-NCC6H4
p-(CH3)2NC6H4
o-FC6H4
3,5-(CH3)2C6H3
p-ClC6H4
p-CH2=CHC6H4
p-CH3COC6H4
2-Furyl
o-CH3OC6H4
1-Naphthy
m-BrC6H4
C6H5
9a
9b
9c
9d
9e
9f
9g
9h
9i
1
85
80
82
80
90
70
87
64
85
90
89
82
70
80
85
90
–
1
1
brown solid; m.p. 88–90 °C (lit.5 89–90 °C); H NMR (400 MHz,
3
1
CDCl3): δ 7.41–7.34 (m, 2H), 6.70–6.63 (m, 2H), 3.07 (s, 6H), 2.99 (s,
6H); 13C NMR (100 MHz, CDCl3): δ 172, 151.2, 129.1, 122.9, 110.9,
40.1, 38.5.
4
1
5
1
6
1.5
1
N,N-Dimethyl-2-fluorobenzamide (9c): Yield (82%); colourless
7
waxy solid; 1H NMR (400 MHz, CDCl3): δ 7.45–7.33 (m, 2H), 7.20
8
2
(t, J = 7.5 Hz, 1H), 7.13–7.09 (m, 1H), 3.13 (s, 3H), 2.94 (s, 3H); 13
C
9
1
NMR (100 MHz, CDCl3): δ 166.7, 158.1 (d, C, J = 246 Hz), 131.2,
128.9, 124.6, 115.8, 115.5, 38.9, 34.9; HRMS (ESI): m/z [M+H+]
Calcd for C9H11FNO: 168.0825; found: 168.0836.
10
11
12
13
14
15
16
17
18
19
9j
9k
9l
1
1
1.5
0.5
2
N,N-Dimethyl-3,5-dimethylbenzamide (9d): Yield (80%); colour-
p-ClC6H4-CH2
1,4-(COOH)2C6H4
p-CH3C6H4
9m
9n
9o
9p
9q
9r
1
less waxy solid; H NMR (400 MHz, CDCl3): δ 7.06–6.97 (m, 3H),
3.17–3.03 (s, 3H), 2.96 (s, 3H), 2.32 (s, 6H); 13C NMR (100 MHz,
CDCl3): δ 172.0, 137.9, 136.3, 130.9, 124.5, 39.5, 35.2, 21.2. HRMS
(ESI): m/z [M+H+] Calcd for C11H16NO: 178.1231; found: 178.1242.
N,N-Dimethyl-4-chlorobenzamide (9e):6 Yield (90%); colourless
1
1
0.5
0.5
0.5
p-(2-C5H4N-CH2)-O-C6H4
o-OHCC6H4
C6H5-CH2CH2
p-CH3OC6H4-CH2
76
72
9s
1
solid: m.p. 56–58 °C (lit.6 56–57 °C); H NMR (400 MHz, CDCl3):
δ 7.44–7.32 (m, 4H), 3.10 (br, s, 3H), 2.96 (br, s, 3H); 13C NMR
(100 MHz, CDCl3): δ 170.1, 135.2, 134.4, 128.33, 128.28, 39.2,
35.1.
a Yields refer to the isolated pure product.
N,N-Dimethyl-4-ethenylbenzamide (9f):9,11 Yield (70%); colourless
and useful contribution to present methodologies for the
conversion of carboxylic acids into corresponding amides.
This protocol is green as it has several advantages over the
previous methods reported which include (i) shorter reaction
times and easy workup, (ii) in-situ generation of dimethyl-
amine, thereby simplifying the operation, (iii) highly water
soluble by-products, and (iv) excellent chemical yields for
wide variety of substrates.
1
solid: m.p. 53–54 °C (lit.11 55–56 °C); H NMR (400 MHz, CDCl3):
δ 7.50–7.34 (m, 4H), 6.72 (dd, J = 17.6, 10.5 Hz, 1H), 5.79 (d, J =
17.6 Hz, 1H), 5.31 (d, J = 10.5 Hz, 1H), 3.10 (br, s, 3H), 2.98 (br, s,
3H); 13C NMR (100 MHz, CDCl3): δ 171.6, 139.0, 136.4, 135.8,
127.7, 126.3, 115.3, 39.8, 35.6.
N,N-Dimethyl-4-acetylbenzamide (9g):8 Yield (87%); brownish vis-
1
cous oil; H NMR (400 MHz, CDCl3): δ 8.04–7.96 (d, J = 8.5 Hz,
2H), 7.55–7.49 (d, J = 8.5 Hz, 2H), 3.13 (s, 3H), 2.96 (s, 3H), 2.63 (s,
3H); 13C NMR (100 MHz, CDCl3): δ 197.4, 170.5, 140.7, 137.6,
128.4, 127.2, 39.3, 35.6, 26.7.
Experimental
N,N-Dimethylfuran-2-carboxamide (9h):10 Yield (64%); colourless
All reagents were purchased from commercial sources and used with-
out any additional purification. All experiments were carried out under
1
viscous oil; H NMR (400 MHz, CDCl3): δ 7.57–7.45 (m, 1H), 6.99
(d, J = 4.0 Hz, 1H), 6.48 (dd, J = 4.0 Hz, 1H), 3.28 (br, s, 3H), 3.10
(br, s, 3H); 13C NMR (100 MHz, CDCl3): δ 160.3, 148.0, 143.7, 116.0,
111.1, 38.9, 36.2.
1
a nitrogen atmosphere to maintain anhydrous conditions. H NMR
and 13C NMR spectra were recorded on a 400-MHz Bruker instrument
with the chemical shifts reported as δ ppm and couplings expressed in
Hertz. The chemical shifts, δ, were recorded relative to tetramethylsi-
lane as an internal standard; all coupling constants, J, are reported in
Hz.
N,N-Dimethyl-2-methoxybenzamide (9i):10 Yield (85%); colourless
1
viscous oil; H NMR (400 MHz, CDCl3): δ 7.39–7.30 (m, 1H), 7.23
(dd, 8.0 Hz, 1H), 6.98 (t, J = 8.0 Hz, 1H), 6.91 (d, J = 8.0 Hz, 1H),
3.83 (s, 3H), 3.12 (s, 3H), 2.85 (s, 3H); 13C NMR (100 MHz, CDCl3):
δ 169.4, 155.2, 130.2, 127.8, 126.2, 120.8, 110.9, 55.5, 38.1, 34.6.
N,N-Dimethyl-1-naphthamide (9j):10 Yield (90%); colourless vis-
cous oil; 1H NMR (400 MHz, CDCl3): δ 7.92–7.82 (m, 3H), 7.82–7.45
(m, 4H), 3.25 (s, 3H), 2.80 (s, 3H); 13C NMR (100 MHz, CDCl3):
δ 170.8, 134.6, 133.3, 129.3, 128.9, 128.3, 126.9, 126.2, 125.1, 124.7,
123.8, 38.8, 34.8.
N,N-Dimethyl-3-bromobenzamide (9k): Yield (89.0%); colourless
viscous oil; 1H NMR (400 MHz, CDCl3): δ 7.61–7.49 (m, 2H), 7.38–
7.31 (m, 1H), 7.31–7.24 (m, 1H), 3.10 (s, 3H), 2.97 (s, 3H); 13C NMR
(100 MHz, CDCl3): 169.7, 138.2, 132.4, 129.9, 125.5, 122.3, 39.4,
35.2. HRMS (ESI): m/z [M+H+] Calcd for C9H11N79BrO: 228.0018;
found: 228.0037.
Synthesis of N-benzoylimidazole (6); typical procedure
1,1′-Carbonyldiimidazole (2.0 g, 0.012 mol) was added to a solution
of benzoic acid (5) (1.0 g, 0.0081 mol) in dichloromethane (6 mL).
The solution was stirred for 1.5 h. Dichloromethane (20 mL) was
added to the reaction mixture followed by water (40 mL). The dichlo-
romethane layer was separated and dried over anhydrous Na2SO4 and
filtered. Distillation of the dichloromethane extract gave 1.3 g (93%)
of N-benzoylimidazole (6) as a colourless pasty liquid. 1H NMR (400
MHz, CDCl3): δ 7.84 (s, 1H) 7.76–7.69 (m, 1H), 7.56–7.53 (m, 2H),
7.46–7.42 (m, 1H) 7.33–7.29 (m, 2H), 6.91 (s, 1H).
N,N-dimethylamination of acids; typical procedure
N,N-Dimethylbenzamide (9l):5 Yield (82%); colourless solid: m.p.
39–40 °C (lit.5 38–39 °C); 1H NMR (400 MHz, CDCl3): δ 7.46–7.33
(m, 5H), 3.11 (br, s, 3H), 3.04–2.88 (s, 3H); 13C (100 MHz, CDCl3):
171.6, 136.3, 129.5, 128.3, 127.0, 39.5, 35.3.
N,N-Dimethyl-4-chlorophenylacetamide (9m): Yield (70%); waxy
solid; 1H NMR (400 MHz, CDCl3): δ 7.37 (dd, J = 2.0, 7.0 Hz, 1H),
7.32–7.26 (m, 1H), 7.26–7.16 (m, 2H), 3.81 (s, 2H), 3.04 (s, 3H), 3.00
(s, 3H); 13C NMR (100 MHz, CDCl3): 170.1, 133.9, 133.5, 130.7,
129.3, 128.2, 126.9, 38.1, 37.5, 35.6; HRMS (ESI): m/z [M+H+] Calcd
for C10H1335ClNO: 198.06816; found: 198.0693.
A solution of benzoic acid (Table 2, entry 12) (1.0 g, 0.0081 mol) and
1,1′-carbonyldiimidazole (2.0 g, 0.012 mol) in dry N,N-dimethylacet-
amide (10 mL) solvent was heated to 160–165 °C and stirred for 1 h.
HPLC analysis of the crude product showed that the reaction had pro-
ceeded to 100% conversion. The resultant solution was cooled to 20–
25 °C and quenched with water (30 mL). The reaction mixture was
extracted with isopropyl acetate (2 × 15 mL). The combined organic
layer was washed with 5% aqueous NaOH solution (2 × 15 mL), dried
over anhydrous Na2SO4 and filtered. The filtrate was evaporated under
reduced pressure to give 0.98 g (82%) of N,N-dimethylbenzamide
(Table 2, entry 12).
N,N,N′,N′-Tetramethylterephthalamide (9n): Yield (80%); colour-
1
All experiments were run on a 1.0 g scale using dry N,N-dimethyl-
acetamide under nitrogen atmosphere with 1,1′-carbonyldiimidazole.
The yields refer to isolated yields as such and/ or recrystallisation. All
less solid: m.p. 145–146 °C (lit.5 145–146 °C); H NMR (400 MHz,
CDCl3): δ 7.45 (s, 4H), 3.12 (br s, 6H), 2.97 (br s, 6H); 13C NMR
(100 MHz, CDCl3): δ 170.8, 137.5, 126.8, 39.5, 35.3.

JOURNAL OF CHEMICAL RESEARCH 2013 159
N,N-Dimethyl-4-methylbenzamide(9o):10 Yield (85%); colourless
viscous oil; 1H NMR (400 MHz, CDCl3): δ 7.35–7.27 (m, 2H), 7.23–
7.15 (m, 2H), 3.09 (br, s, 3H), 2.98 (br, s, 3H), 2.37 (s, 3H); 13C NMR
(100 MHz, CDCl3): δ 171.8, 139.6, 133.3, 128.9, 127.1, 39.3, 35.1,
21.3.
Received 20 October 2012; accepted 9 January 2013
Paper 1201581 doi: 10.3184/174751913X13602686612047
Published online: 12 March 2013
References
N,N-Dimethyl-4-(pyridine-2-yl-methoxy)benzamide (9p): Yield
(90%); waxy brownish solid; 1H NMR (400 MHz, DMSO-d6): δ 8.59
(d, J = 4.0 Hz, 1H), 7.98–7.74 (m, 1H), 7.53 (d, J = 8.0, 1H), 7.43–
7.27 (m, 3H) 7.06 (d, J = 8.0 Hz, 2H), 5.22 (s, 2H), 2.94 (s, br, 6H);
13C NMR (100 MHz, DMSO-d6): δ 169.8, 158.8, 156.3, 149.1, 136.9,
128.9, 128.8, 123.0, 121.7, 114.2, 70.3, 40.1, 38.6. HRMS (ESI): m/z
[M+H+] Calcd for C15H17N2O2: 257.1285; found: 257.1293.
N,N-Dimethyl-3-phenylpropanamide (9r):12 Yield (76%); brownish
1
2
G.M. Coppinger, J. Am. Chem. Soc., 1954, 76, 1372.
H.H. Bosshard, R. Mory, M. Schmidt and H. Zollinger, Helv. Chim. Acta,
1959, 42, 1653.
3
4
5
J.I. Le and H.A. Park, Bull. Kor. Chem. Soc., 2001, 22, 421.
R.A. Guobin, Chin. J. Org. Chem., 1996, 16, 68.
T. Kumagai, T. Anki, T. Ebi, A. Konishi, K. Matsumoto, H. Kurata,
T. Kubo, K. Katsumoto, C. Kitamura and T. Kawase, Tetrahedron, 2010,
66, 8968.
1
6
7
B. Kaboudin and H. Haghighat, J. Iran. Chem. Soc. 2012 (in press).
M.T. Xavier, B. Julien, R. Thomas, S. Jordi, M. Jean and L. Frederic,
Chem. Commun., 2012, 48, 11781.
viscous oil; H NMR (400 MHz, CDCl3): δ 7.31 (m, 2H), 7.24–7.16
(m, 3H), 2.97 (t, J = 8.2 Hz, 2H), 2.95 (s, 3H), 2.93 (s, 3H), 2.62 (t,
J = 8.2 Hz, 2H); ESIMS: m/z Calcd [M+]: 177.1; found: 178.1
[M+1].
8
D.N. Sawant, Y.S. Wagh, K.D. Bhatte and B.M. Bhanage, J. Org. Chem.,
2011, 76, 5489.
N,N-Dimethyl-2-(4-methoxyphenyl)acetamide (9s):13 Yield (72%);
brownish oil; 1H NMR (400 MHz, CDCl3): δ 7.17 (d, J = 8.5 Hz, 2H),
6.86 (d, J = 8.5 Hz, 2H), 3.76 (s, 3H), 3.65 (s, 2H), 2.99 (s, 3H), 2.95
(s, 3H); ESIMS: m/z Calcd [M+]: 193.1; found: 194.1 [M+1].
9
S.E. Denmark and C.R. Butler, J. Am. Chem. Soc., 2008, 130, 3690.
10 Z. Liu, J. Zhang, S. Chen, E. Shi, Y. Xu and X. Wan, Angew. Chem., Int.
Ed., 2012, 51, 3232.
11 T. Ishizone, S. Wakabayashi, A. Hirao, and S. Nakahama, Macromol.,
1991, 24, 5015.
12 Y. Sunada, H. Kawakami, T. Imaoka, Y. Motoyama and H. Nagashima,
Angew. Chem., Int. Ed., 2009, 48, 9511.
13 K.H. Shaughnessy, B.C. Hamann and J.F. Hartwig, J. Org. Chem., 1998,
63, 6546.
We thank Sudhir Nambiar, R. Sridharan, Bill Moss and
Ramachandra Puranik for useful discussions and for help with
the manuscript preparation.

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