A Practical Approach for the Transamidation of N, N-Dimethyl Amides with Primary Amines Promoted by Sodium tert-Butoxide under Solvent-Free Conditions

Article abstract of DOI:10.1055/s-0040-1705892

A practical sodium tert-butoxide (NaO t Bu)-mediated protocol is disclosed for the transamidation of various N, N-dimethyl amides with primary amines to afford the corresponding amides in moderate to good yields at room temperature under solvent-free conditions. This protocol features a facile work-up procedure and good functional group compatibility, especially for N, N-dimethyl amides with long-chain alkyl groups and heteroatom-containing amines. Notably, a few representative gram-scale reactions proceed smoothly to furnish the desired amides in high yields, which demonstrates the potential of this process for further practical applications. Several control experiments are carried out and a plausible mechanism is provided.

Full text of DOI:10.1055/s-0040-1705892

SYNTHESIS
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Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart
2020, 52, A–I
special topic
A
Amide Bond Formation
R. Zhang et al.
Special Topic
Synthesis
A Practical Approach for the Transamidation of N,N-Dimethyl
Amides with Primary Amines Promoted by Sodium tert-Butoxide
under Solvent-Free Conditions
Rui Zhanga
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O
H
R2
NaOtBu, rt
N
45–90% yield
23 examples
R1 NH2
+
Jun-Chao Zhanga
Wei-Yi Zhanga
Yu-Qing Hea
Hua Cheng*a
Cheng Chen*b
R1
N
R2
neat
O
R1 = aliphatic, (hetero)aryl; R2 = H or alkyl
Transition-metal-free and solvent-free
Uses 1.5 equiv of NaOtBu and 3.0 equiv of the N,N-disubstituted amide
Compatible with long-chain alkyl groups and heteroatom-containing amines
Gram-scale reactions with an easy work-up procedure
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Yu-Cheng Guc
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a Department of Chemical Engineering and Food Science, Hubei University
of Arts and Science, Xiangyang 441053, P. R. of China
cch510@126.com
b State Key Laboratory of Advanced Technology for Materials Synthesis and
Processing, Wuhan University of Technology, 122 Luoshi Road, Wuhan
430070, P. R. of China
chengchen@whut.edu.cn
c Syngenta, Jealott’s Hill International Research Centre, Bracknell,
Berkshire, RG42 6EY, UK
This paper is dedicated to Professor Youyou Tu, the 2015 Nobel Prize
Laureate of Physiology or Medicine, on the occasion of her 90th birthday
Published as part of the Special Topic
Recent Advances in Amide Bond Formation
Corresponding Author
CDeMheepanailgrtcmCch
e
e5
n
n1t0
o
@f 1C2h6e.mcoicmal Engineering and Food Science, Hubei University of Arts and Science, Xiangyang 441053, P. R. of China
quirement of stoichiometric amounts of coupling reagents,
thus leading to the production of numerous byproducts.3a
In recent decades, non-traditional methods to synthesize
the amide bond have gained significant attention.4 Among
these, the transamidation of amides with amines has
served as a convenient and straightforward alternative,5
which has been utilized in different areas, such as materials
science,6 polymer synthesis,7 protein engineering8 and en-
zymatic transformations.9 Therefore, numerous metal-
based catalysts, including Al-,10 Sc-,10a Ti-,10a Hf-,11 Ce-,12 Zr-
Received: 29.05.2020
Accepted after revision: 22.07.2020
Published online: 08.09.2020
DOI: 10.1055/s-0040-1705892; Art ID: ss-2020-c0297-st
Abstract A practical sodium tert-butoxide (NaOtBu)-mediated proto-
col is disclosed for the transamidation of various N,N-dimethyl amides
with primary amines to afford the corresponding amides in moderate to
good yields at room temperature under solvent-free conditions. This
protocol features a facile work-up procedure and good functional group
compatibility, especially for N,N-dimethyl amides with long-chain alkyl
groups and heteroatom-containing amines. Notably, a few representa-
tive gram-scale reactions proceed smoothly to furnish the desired am-
ides in high yields, which demonstrates the potential of this process for
further practical applications. Several control experiments are carried
out and a plausible mechanism is provided.
,
13 Nb-,14 Ni-15, Cu-16, Fe-17 and Pd-based18 catalysts, as well
as heterobimetallic complexes,19 have been reported for
this transformation. However, many of these methods suf-
fer from the involvement of noble metal catalysts, high
temperatures or complicated work-up procedures. Accord-
ingly, transition-metal-free protocols have also been uti-
lized to facilitate transamidations.20 Among these protocols,
only aliphatic amines were compatible in some
cases.20b,e,i,o,q Besides, additional solvents,20a–d,20f,h,20l–n
microwave irradiation,20g,h high temperatures20q or activat-
ed amides20j–m,20o,p were usually used. Therefore, it is still
highly desirable to develop mild and economic approaches
for the transamidation of amides with aromatic amines
(weaker nucleophiles than aliphatic amines) under transi-
tion-metal-free and solvent-free conditions.
Key words NaOtBu, transamidation, N,N-dimethyl amides, primary
amines, solvent-free, gram-scale
The amide bond, an undoubtedly fundamental motif in
Nature, is extensively represented in natural products,
pharmaceuticals, agrochemicals and functional materials.1
Amide bond formation has been recognized as one of the
most frequently used transformations in the pharmaceuti-
cal industry and in academic research.2 As a consequence,
numerous synthetic methods have been developed for the
construction of the amide bond. Among them, the most
general approach is the direct condensation between a car-
boxylic acid and an amine, a process known as direct ami-
dation.3 However, this approach is hampered by the re-
In 2019, Yu’s group21 reported the KOtBu-promoted
transamidation of tertiary amides with aromatic amines at
temperatures ranging from room temperature to 130 °C
(Scheme 1a). In this protocol, 4.0 equivalents of KOtBu and
© 2020. Thieme. All rights reserved. Synthesis 2020, 52, A–I
Georg Thieme Verlag KG, Rüdigerstraße 14, 70469 Stuttgart, Germany

B
R. Zhang et al.
Special Topic
Synthesis
10–15 equivalents of the tertiary amides were utilized
without any solvent, with microwave irradiation being es-
sential for N-acetylation and N-benzoylation. In the same
year, the Dash group22 reported another KOtBu-promoted
and solvent-free transamidation of primary or tertiary am-
ides with amines at room temperature (Scheme 1, b). In
their report, 1.5 equivalents of KOtBu and 10–20 equiva-
lents of the amide were used. With an aim to develop a
more practical protocol for this transamidation, we have
studied the NaOtBu-promoted transamidation of N,N-
disubstituted amides with primary amines (Scheme 1, c).
The reactions proceeded smoothly at room temperature
under solvent-free conditions. More significantly, 1.5
equivalents of NaOtBu (the same or even lower than the
amount of KOtBu in Schemes 1, a and b) and only 3.0 equiv-
alents of the N,N-disubstituted amides (being much lower
than the amounts in Schemes 1, a and b) were required to
efficiently deliver a range of amide products from various
N,N-dimethyl amides (including examples with long-chain
alkyl groups) and primary amines (especially heteroatom-
containing amines). Gratifyingly, gram-scale reactions
could be smoothly accomplished and a simple work-up
procedure was utilized. Additional investigations were also
conducted in an effort to understand the reaction mecha-
nism.
resulted in a slightly better result (entry 2), while an even
weaker base (LiOtBu) only produced a moderate yield of 3a,
with 46% of 1a remaining (entry 3). Unfortunately, other
bases including carbonate salts (entries 4–6), hydroxides
(entries 7–9) and organic bases (entries 10 and 11) did not
promote this transamidation. It stands to reason that NaOt-
Bu promotes this transamidation in the most effective
manner. Intending to further increase the yield of 3a, we
continued to investigate other parameters. Accordingly, dif-
ferent amounts of NaOtBu were then screened (entries 12–
15). When the amount of NaOtBu was reduced to 1.00
equivalent or 1.25 equivalents, the yield of 3a decreased to
76% (entry 12) and 88% (entry 13). This result indicated
that decreasing the amount of NaOtBu was detrimental to
the generation of 3a. Increasing the amount of NaOtBu from
1.50 equivalents to 1.75 equivalents and 2.00 equivalents
Table 1 Optimization of the Reaction Conditionsa
H
O
NH2
N
H
base (y equiv)
rt, 3 h
+
N
H
O
1a (1.00 equiv)
2a (x equiv)
3a
Entry
DMF (x equiv) Base (y equiv)
Yieldsb
3a
Unreacted 1a
(a) Yu's work, 2019
1
2
4.00
4.00
4.00
4.00
4.00
4.00
4.00
4.00
4.00
4.00
4.00
4.00
4.00
4.00
4.00
3.00
1.50
1.00
3.00
KOtBu (1.50)
NaOtBu (1.50)
LiOtBu (1.50)
Cs2CO3 (1.50)
Na2CO3 (1.50)
K2CO3 (1.50)
LiOH (1.50)
88%
95%
48%
6%
3%
O
H
NH2
KOtBu (4.0 equiv)
N
R2
R1
+
R1
N
R2
O
3
46%
99%
98%
97%
96%
99%
99%
97%
98%
23%
11%
2%
10–15 equiv
High temperature when R2 = Me
Microwave irradiation involved when R2 = Ph
O
c
4
–
c
(b) Dash's work, 2019
O
5
–
c
6
–
F3C
(10.0 equiv)
NH2
Ph/Me/H
NMe2
H
H
c
N
CF3
N
H/Me/Ph
7
–
(10.0–20.0 equiv)
R
H2N
R
R
KOtBu (1.5 equiv), rt
c
KOtBu (1.5 equiv), rt
8
NaOH (1.50)
KOH (1.50)
–
O
O
Additional extraction to remove excess DMF or DMAc
c
9
–
(c) This work:
c
10
11
12
13
14
15
16
17
18
19d
DIPEA (1.50)
DBU (1.50)
–
O
H
NaOtBu (1.5 equiv)
N
R2
45–90% yield
23 examples
R1 NH2
+
R1
c
–
N
R2
neat
O
NaOtBu (1.00)
NaOtBu (1.25)
NaOtBu (1.75)
NaOtBu (2.00)
NaOtBu (1.50)
NaOtBu (1.50)
NaOtBu (1.50)
NaOtBu (1.50)
76%
88%
95%
96%
97%
77%
55%
87%
(3.0 equiv)
R1 = aliphatic, (hetero)aryl; R2 = H or alkyl
Transition-metal-free Compatible with long-chain alkyl groups
Gram-scale reactions with an easy work-up procedure
c
–
Scheme 1 Previous studies on the transamidation of amides and the
strategy utilized in this work
c
–
16%
38%
9%
At the outset of our studies, the reaction of aniline (1a)
and anhydrous N,N-dimethylformamide (DMF) (2a) was se-
lected as a model reaction to optimize the reaction condi-
tions (Table 1). With KOtBu (1.50 equiv) as the base, the re-
action of 1a (1.00 equiv) and 2a (4.00 equiv) was initially
conducted at room temperature under argon for 3 hours,
leading to an 88% yield of amide 3a and 6% of unreacted 1a
(entry 1). To our delight, replacing KOtBu with milder NaOtBu
a Reaction conditions: 1a (2.15 mmol, 1.0 equiv), 2a (x equiv) and base (y
equiv) were added to a 10 mL round-bottom flask in a glovebox. The result-
ing mixture was stirred at room temperature under argon for 3 h.
b 1H NMR yields using 1,3,5-trimethoxybenzene as an internal standard (av-
erage of two consistent runs).
c The starting material was not detected in the crude 1H NMR spectrum.
d Reaction under air instead of argon (with a drying tube containing CaCl2).
© 2020. Thieme. All rights reserved. Synthesis 2020, 52, A–I

C
R. Zhang et al.
Special Topic
Synthesis
led to almost identical yields of 3a (entries 14 and 15 vs en-
try 2). Therefore, 1.50 equivalents of NaOtBu was selected
as the optimum amount of base. Next, the substrate ratio of
2a/1a was evaluated (entries 16–18). Interestingly, reducing
the ratio from 4:1 to 3:1 resulted in an even better yield of
3a (97%) and without the detection of any unreacted 1a ac-
uct yields. Under the standard conditions, 3-methylaniline
(1j) and 2-methylaniline (1k) delivered the desired prod-
ucts 3m and 3n in yields of 86% and 80%, respectively. In ad-
dition, anilines with two substituents on the aromatic ring
furnished the corresponding products 3l and 3m in good
yields. Amines with privileged scaffolds, such as 4-phe-
nylaniline (1n), 4-phenoxyaniline (1o) and p-aminodiphe-
nylamine (1p), were employed to further test the scope of
this transformation. To our delight, these three substrates
were converted into the desired products 3n–p in yields of
75–86%. In particular, only the mono-formylated product
3p was detected and isolated in 78% yield from p-aminodi-
phenylamine (1p), which indicated that secondary amines
probably could not be applied in this reaction. Meanwhile,
two heterocyclic amines, namely pyridin-2-amine (1q) and
quinolin-8-amine (1r), were efficiently transformed into N-
(pyridin-2-yl)formamide (3q) and N-(quinolin-8-yl)forma-
mide (3r), respectively. Primary aliphatic amines were also
evaluated using 2-phenylethan-1-amine (1s) and hexan-1-
amine (1t) as the substrates, with N-phenethylformamide
(3s) and N-hexylformamide (3t) being isolated in 81% and
94% yields, respectively.
To further extend the scope of this protocol, the reactiv-
ity of several N,N-dialkyl-substituted amides was examined
(Scheme 3). Aniline (1a) was selected as the amine sub-
strate for reactions with N,N-dimethylacetamide (2u), N,N-
dimethylbutyramide (2v) and N,N-dimethyldecanamide
(2w). As expected, the corresponding transamidation prod-
ucts were obtained, albeit in moderate yields (40–65%). To
improve these moderate yields of the desired products 3u–
w, further optimization of the reaction conditions (increas-
1
cording to the crude H NMR spectrum (entry 16 vs entry
2). When the ratio was further decreased to 1.5:1 or 1:1,
the yields of 3a were reduced to 77% and 55%, respectively
(entries 17 and 18 vs entry 1). When the reaction was con-
ducted under dry air instead of argon, a slightly reduced
yield of 3a was obtained (entry 19). Therefore, the opti-
mized conditions were as follows: NaOtBu (1.50 equiv), a
primary amine (1.00 equiv), N,N-dimethyl amide (3.00
equiv), room temperature, 3 h (entry 16).
With optimized reaction conditions in hand, the sub-
strate scope and limitations of this protocol were explored.
Firstly, the reactions of various (hetero)aromatic amines
and DMF were attempted, with the desired products being
obtained in good to excellent yields (Scheme 2). Anilines
bearing an electron-donating group such as methyl (1b),
methoxy (1c) or tert-butyl (1d) reacted well with DMF to
provide the corresponding products in 78–92% yield. For
anilines bearing an electron-withdrawing group, including
F (1e), Cl (1f), Br (1g), OCF3 (1h) or CN (1i), the transamida-
tion reactions also proceeded smoothly, providing the de-
sired formylated products in high yields (72–97%). These re-
sults imply that the electronic properties of the substitu-
ents only marginally affected the reactivity of the anilines.
It also appeared that the position of the substituent on the
phenyl ring did not have a considerable impact on the prod-
O
H
NaOtBu (1.50 equiv)
N
H
R
NH2
+
R
N
H
neat, rt, 3 h
O
1 (1.00 equiv)
2 (3.00 equiv)
3
H
H
H
H
N
H
N
H
N
H
N
H
H
N
H
H
H
N
H
O
O
O
O
O
O
O
Cl
Br
MeO
F
3a (95%)
3b (92%)
3h (97%)
3c (85%)
3d (78%)
3e (90%)
3f (72%)
H
H
H
H
H
N
H
N
N
H
N
H
N
H
N
H
H
O
O
O
O
O
F3CO
Br
NC
3g (80%)
3i (88%)
3j (86%)
3k (80%)
3l (84%)
H
H
N
N
H
H
H
H
N
H
N
H
N
N
H
H
O
O
O
O
O
N
O
Br
H
3m (65%)
3n (75%)
3o (86%)
3p (78%)
3q (71%)
O
H
H
N
H
N
H
N
H
H
O
O
N
3r (71%)
3s (81%)
3t (94%)
Scheme 2 Exploration of the scope of the NaOtBu-mediated transamidation of anilines with DMF. The reactions were performed under argon using a
Schlenk line inside a fume hood. Yields are those of isolated products obtained under standard reaction conditions.
© 2020. Thieme. All rights reserved. Synthesis 2020, 52, A–I

D
R. Zhang et al.
Special Topic
Synthesis
ing the reaction temperature and/or equivalents of NaOtBu)
was conducted, leading to products 3u, 3v and 3w being ob-
tained in increased yields of 86%, 81% and 72%, respectively.
Interestingly, the reaction could be conducted under dry air,
with only a slightly lower yield being obtained compared
with that under argon (entry 2 vs entry 1). In order to verify
whether a radical process was involved in this transforma-
tion, different equivalent amounts of TEMPO were added to
the reaction mixture (entries 3–5). However, the addition of
TEMPO had no significant influence on the yield of 3a (en-
tries 3–5). Moreover, another radical scavenger, 1,1-di-
phenylethylene, was also utilized, but again, no significant
decrease in the yield of 3a was observed (entry 6). There-
fore, a radical-involved process is excluded in our NaOtBu-
mediated transamidation. Probably, NaOtBu interacts with
the primary amine at room temperature, which results in
the enhanced nucleophilicity of the amine.
H
O
NH2
NaOtBu (1.50–2.50 equiv)
N
R2
+
N
R2
neat, rt to 80 °C, 3–12 h
O
3u: R2 = Me, 65%,a 86%b
3v: R2 = n-propyl, 56%,a 81%c
3w: R2 = n-nonyl, 40%,a 72%c
1a (1.00 equiv) 2 (3.00 equiv)
Scheme 3 NaOtBu-promoted transamidation of N,N-dimethyl amides
with aniline (1a). The reactions were performed under argon using a
Schlenk line inside a fume hood. a Yields of the isolated products under
the standard conditions. b Yields of the isolated products using NaOtBu
(2.00 equiv) at 80 °C for 12 h. c Yields of the isolated products using
NaOtBu (2.50 equiv) at 80 °C for 12 h.
Table 2 Control Experiments
To demonstrate the practical value of our protocol, we
selected a few representative reactions and scaled them up
to 20 mmol (Scheme 4). Firstly, the model reaction of 1a (20
mmol) and 2a (60 mmol) was carried out in the presence of
NaOtBu (30 mmol). Interestingly, 20 mmol of 1a was fully
converted at room temperature after 3 hours, affording the
target amide 3a in 94% yield (2.27 g). Similarly, the reaction
of a mixture of NaOtBu, 4-methylaniline (1b) and DMF also
proceeded smoothly to deliver N-p-tolylformamide (3b) in
88% yield (2.38 g) when performed on a 20 mmol scale.
Treatment of 1q with DMF and of 1a with 2u was also ap-
plicable to reactions on a 20 mmol scale, albeit with slightly
reduced yields of the corresponding products 3q and 3u be-
ing obtained in comparison with the respective reactions
on 2.15 mmol scale.
NaOtBu (1.50 equiv)
O
H
radical scavenger (x equiv)
N
H
+
NH2
N
H
neat, atmosphere, rt, 3 h
O
1a (1.00 equiv) 2a (3.00 equiv)
3a
Entry
Radical scavenger Atm
Yieldsa
(equiv)
3a
Unreacted 1a
1
2
3
4
5
6
–
argon
dry airb
argon
argon
argon
argon
97%
90%
87%
86%
85%
90%
–
–
5%
TEMPO (1.00)
TEMPO (2.00)
TEMPO (3.00)
10%
11%
11%
7%
1,1-diphenyleth-
ylene (1.00)
Subsequently, control experiments were performed to
gain more insight into the reaction mechanism (Table 2).
a 1H NMR yields using 1,3,5-trimethoxybenzene as an internal standard.
b Equipped with a drying tube containing CaCl2.
H
NaOtBu
(30 mmol)
O
N
H
On the basis of the above observations and related pre-
vious reports,10b,21–23 a plausible reaction mechanism in-
volving coordination of the N,N-dimethyl amide with NaOtBu
and subsequent nucleophilic addition of an activated amine
is proposed (Scheme 5). It has already been established that
Na+ can form strong interactions with the oxygen atom of
DMF and its derivatives, and that such interactions lead to
an overall increase in the extent of the positive charge on
the nitrogen atom.24 In related transamidations, KOtBu is a
strong base and a good single-electron transfer (SET) re-
agent,25 so it is reasonable to assume that deprotonation of
the amine is the first step.21,22 However, compared with
KOtBu, NaOtBu is a milder base and does not tend to act as a
SET reagent. Therefore, NaOtBu probably activates (not
deprotonates) amine 1 via coordination to generate inter-
mediate 4. Meanwhile, amide 2 is transformed into inter-
mediate 2′ via a coordination interaction with NaOtBu.24,26
Next, activated amine 4 reacts with 2′ to deliver the unsta-
ble tetrahedral intermediate 5 via nucleophilic addition,
NH2
+
+
+
N
H
neat, Ar, rt, 3 h
O
1a (20 mmol, 1.9 mL)
2a (60 mmol, 4.7 mL)
3a (18.7 mmol, 2.27 g)
Yield: 94%
H
NaOtBu
(30 mmol)
O
N
H
NH2
N
H
neat, Ar, rt, 3 h
O
2 (60 mmol, 4.7 mL)
3b (17.6 mmol, 2.38 g)
1b (20 mmol, 2.2 mL)
Yield: 88%
H
NaOtBu
(30 mmol)
O
N
N
H
N
NH2
N
H
neat, Ar, rt, 3 h
O
3q (12.2 mmol, 1.49 g)
1q (20 mmol, 1.9 mL)
2a (60 mmol, 4.7 mL)
Yield: 61%
H
N
NaOtBu
(30 mmol)
O
NH2
+
N
neat, Ar, rt, 3 h
O
3u (10.8 mmol, 1.46 g)
1a (20 mmol, 1.9 mL)
2u (60 mmol, 5.6 mL)
Yield: 54%
Scheme 4 Representative reactions on 20 mmol scale
© 2020. Thieme. All rights reserved. Synthesis 2020, 52, A–I

E
R. Zhang et al.
Special Topic
Synthesis
followed by proton transfer to form intermediate 6.27 Final-
ly, intermediate 6 eliminates a molecule of dimethylamine
7 to afford the desired product 3.27
Calculation of the NMR Yields of 3a During Optimization of the
Reaction Conditions; General Procedure
After completion of the transamidation, the reaction mixture was
quenched by the addition of water (5 mL) and EtOAc (10 mL). The or-
ganic layer was separated and the aqueous layer was extracted with
EtOAc (2 × 10 mL). The organic layers were combined and washed
with brine (20 mL), dried over Na2SO4, and concentrated under re-
duced pressure. 1,3,5-Trimethoxybenzene (168.0 mg, 1.0 mmol) and
CDCl3 (1.5 mL) were added. Subsequently, 0.5 mL of the upper solu-
tion was added to an NMR tube, and this sample was used to record
the crude 1H NMR spectra for determination of NMR yields (based on
the exact amount of 1,3,5-trimethoxybenzene).
O
R
N
2
Na
O
NaOtBu
OtBu
O
R
N
H
2'
Na
OtBu
R' NH2
R
N
R
N
NH2
H
4
R'
1
5
Amides 3a–w; General Procedure
O
Inside an argon-filled glovebox, NaOtBu (309.6 mg, 3.23 mmol),
amine 1 (2.15 mmol) and amide 2 (6.45 mmol) were added succes-
sively to a 10 mL Schlenk flask containing a magnetic stir bar. The re-
action mixture was stirred at room temperature for 3 h (monitored by
TLC) and then quenched by the addition of water (5 mL) and EtOAc
(10 mL). The organic layer was separated, washed with brine (20 mL),
dried over Na2SO4 and concentrated under reduced pressure. The resi-
due was subjected to column chromatography (silica gel, 200–300
mesh, petroleum ether/EtOAc = 10:1 to 4:1) to afford the desired
product 3a–w.
R
O
Proton transfer
R'
R'
H
R
N
N
N
H
H
3
6
N
H
7
Scheme 5 A plausible reaction mechanism
In conclusion, a practical NaOtBu-promoted protocol
has been reported for the transamidation of primary
amines with N,N-dimethyl amides. Accordingly, a wide
range of amide products has been obtained in moderate to
good yields at room temperature under solvent-free condi-
tions. Moreover, a facile work-up procedure was utilized
and various primary amines (including heteroatom-
containing amines) and N,N-dimethyl amides (including ex-
amples with long-chain alkyl groups) were compatible.
More significantly, this protocol could be smoothly applied
to gram-scale reactions, delivering a set of selected amides
in high yields, which demonstrates the practical value of
this process for further applications. Finally, several control
experiments excluded the possibility of a radical-involved
process, and instead, a mechanism involving deprotonation,
coordination and nucleophilic addition has been proposed.
Gram-Scale Reaction under Argon; Typical Procedure
To a solution of aniline (1a) (1.86 g, 20 mmol) and DMF (2a) (4.65 mL,
60 mmol) was added NaOtBu (2.88 g, 30 mmol) in a glovebox. The re-
action mixture was stirred under argon for 3 h (monitored by TLC) at
room temperature. After the complete consumption of aniline, the re-
action was quenched by the addition of water (10 mL) and EtOAc (40
mL). The organic layer was separated and washed with brine (2 × 20
mL), dried over Na2SO4 and concentrated under reduced pressure. The
residue was purified by column chromatography (200–300 mesh sili-
ca gel, petroleum ether/EtOAc = 10:1 to 4:1) to afford N-phenylforma-
mide (3a) in 94% yield. Similar procedures were followed when this
transamidation was conducted on a 20 mmol scale using p-toluidine
(1b), pyridin-2-amine (1q) or N,N-dimethylacetamide (2u) as sub-
strates, affording N-p-tolylformamide (3b), N-(pyridin-2-yl)forma-
mide (3q) and N-phenylacetamide (3u) in 88%, 61% and 54% yields,
respectively.
Radical Studies with TEMPO or 1,1-diphenylethylene; General Pro-
cedure
The reactions were set up using standard Schlenk techniques or in an
argon-filled glovebox unless otherwise mentioned. All standard re-
agents and solvents were obtained from commercial suppliers and
used directly without further purification. TLC was performed using
Qingdao Haiyang Chemical Co., Ltd Silica gel as adsorbent. Column
chromatography was carried out using Qingdao Haiyang Chemical
Co., Ltd silica gel (200–300 mesh). Melting points were obtained using
a Buchi M-560 melting point apparatus without calibration. Nuclear
magnetic resonance (NMR) spectra were recorded on a Bruker Avance
500 spectrometer in CDCl3 or DMSO-d6, with tetramethylsilane (TMS)
as an internal reference. Multiplicities are designated using the fol-
lowing abbreviations: s = singlet, br s = broad singlet, d = doublet, t =
triplet, q = quartet, dd = doublet of doublets, td = triplet of doublets, m
= multiplet. High-resolution mass spectrometry (HRMS) was per-
formed with Bruker Daltonics microTOF-QII or Thermo Fisher Q Exac-
tiveTM UHMR OrbitrapTM instruments.
To a solution of aniline (1a) (200.2 mg, 2.15 mmol) and DMF (2a)
(0.49 mL, 6.45 mmol) in a 10 mL round-bottomed flask equipped
with a magnetic stir bar were added NaOtBu (309.6 mg, 3.2 mmol)
and TEMPO (335.9 mg, 2.15 mmol) in a glovebox. The reaction mix-
ture was stirred under argon at room temperature for 3 h (monitored
by TLC) and then quenched by the addition of water (0.5 mL) and
EtOAc (10 mL). The organic layer was separated and washed with
brine (2 × 10 mL), dried over Na2SO4 and concentrated under reduced
pressure. 1,3,5-Trimethoxybenzene (168.0 mg, 1.0 mmol) and CDCl3
(1.5 mL) were added. Subsequently, 0.5 mL of the upper solution was
added to an NMR tube, and this sample was used to record the crude
1H NMR spectrum for determination of the NMR yield (based on the
exact amount of 1,3,5-trimethoxybenzene). A similar procedure was
utilized for reactions in which 2.00 or 3.00 equivalents of TEMPO was
used.
© 2020. Thieme. All rights reserved. Synthesis 2020, 52, A–I

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R. Zhang et al.
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Synthesis
N-Phenylformamide (3a)20e
1H NMR (500 MHz, CDCl3):  (rotamer 1) = 8.57 (d, J = 11.4 Hz, 1 H),
8.34 (d, J = 1.5 Hz, 1 H), 7.53–7.48 (m, 2 H), 7.06–7.04 (m, 2 H).
1H NMR (500 MHz, CDCl3):  (rotamer 2) = 8.41 (s, 1 H), 7.55 (br s, 1
Obtained as a 1:1 mixture of two rotamers.
Yield: 248 mg (95%); brown solid; mp 49.0–50.0 °C.
1H NMR (500 MHz, CDCl3):  (rotamer 1) = 8.37 (d, J = 1.9 Hz, 1 H),
7.37–7.35 (m, 2 H), 7.14 (td, J = 7.4, 1.3 Hz, 1 H), 7.11–7.08 (m, 2 H).
1H NMR (500 MHz, CDCl3):  (rotamer 2) = 8.70 (d, J = 11.4 Hz, 1 H),
8.44 (br s, 1 H), 7.58–7.52 (m, 2 H), 7.34–7.31 (m, 2 H), 7.21–7.17 (m,
1 H).
H), 7.09–7.07 (m, 2 H), 7.02–6.99 (m, 2 H).
13C NMR (126 MHz, CDCl3):  (mixture of rotamers) = 162.9, 160.4 (d,
J = 244.9 Hz), 159.6 (d, J = 244.3 Hz), 159.0, 132.8 (d, J = 3.0 Hz), 132.7
(d, J = 2.8 Hz), 121.8 (d, J = 7.9 Hz), 121.2 (d, J = 8.2 Hz), 116.5 (d, J =
22.9 Hz), 115.8 (d, J = 22.6 Hz).
HRMS (ESI+): m/z [M + H]+ calcd for C7H7FNO: 140.05062; found:
140.05045.
13C NMR (126 MHz, CDCl3):  (mixture of rotamers) = 162.7, 159.1,
136.9, 136.7, 129.7, 129.1, 125.3, 124.8, 120.0, 118.8.
HRMS (ESI+): m/z [M + H]+ calcd for C7H8NO: 122.06004; found:
122.05993.
N-(4-Chlorophenyl)formamide (3f)28
Obtained as a 1:1 mixture of two rotamers.
Yield: 248 mg (72%); white solid, mp 66.9–69.6 °C.
1H NMR (500 MHz, CDCl3):  (rotamer 1) = 8.67 (d, J = 11.9 Hz, 1 H),
8.27 (s, 1 H), 7.52–7.49 (m, 2 H), 7.29 (s, 2 H).
1H NMR (500 MHz, CDCl3):  (rotamer 2) = 8.40 (s, 1 H), 7.40 (br s, 1
H), 7.34 (d, J = 8.9 Hz, 2 H), 7.06 (s, 2 H).
13C NMR (126 MHz, CDCl3):  (mixture of rotamers) = 162.3, 158.9,
135.4, 135.3, 130.8, 129.9, 129.8, 129.2, 121.2, 120.1.
HRMS (ESI–): m/z [M – H]+ calcd for C7H5ClNO: 154.00652, found:
154.00555.
N-p-Tolylformamide (3b)21
Obtained as a 1:1 mixture of two rotamers.
Yield: 267 mg (92%); white solid; mp 58.0–59.4 °C.
1H NMR (500 MHz, CDCl3):  (rotamer 1) = 8.62 (d, J = 11.5 Hz, 1 H),
8.14 (s, 1 H), 7.42 (d, J = 8.2 Hz, 2 H), 7.10 (d, J = 7.8 Hz, 2 H), 2.32 (s, 3
H).
1H NMR (500 MHz, CDCl3):  (rotamer 2) = 8.34 (s, 1 H), 7.32 (br s, 1
H), 7.16–7.12 (m, 2 H), 6.98 (d, J = 8.2 Hz, 2 H), 2.33 (s, 3 H).
13C NMR (126 MHz, CDCl3):  (mixture of rotamers) = 162.7, 158.9,
135.2, 134.5, 134.1, 130.3, 129.6, 120.1, 119.2, 20.9, 20.8.
HRMS (ESI+): m/z [M + H]+ calcd for C8H10NO: 136.07569; found:
136.07551.
N-(4-Bromophenyl)formamide (3g)28
Obtained as a 1.5:1 mixture of two rotamers.
Yield: 350 mg (80%); yellow solid; mp 116.7–119.0 °C.
N-(4-Methoxyphenyl)formamide (3c)28
1H NMR (500 MHz, CDCl3):  (major rotamer) = 8.38 (d, J = 1.7 Hz, 1
H), 7.48–7.45 (m, 4 H), 6.98–6.96 (m, 1 H).
Obtained as a 1:1 mixture of two rotamers.
1H NMR (500 MHz, CDCl3):  (minor rotamer) = 8.65 (d, J = 11.4 Hz, 1
H), 7.91 (br s, 1 H), 7.50–7.46 (m, 4 H).
13C NMR (126 MHz, CDCl3):  (mixture of rotamers) = 162.1, 158.8,
135.8, 135.7, 132.8, 132.1, 121.5, 120.4, 118.3, 117.5.
HRMS (ESI+): m/z [M + H]+ calcd for C7H7BrNO: 199.97055; found:
199.97038.
Yield: 275 mg (85%); yellow solid; mp 78.8–81.5 °C.
1H NMR (500 MHz, CDCl3):  (rotamer 1) = 8.49 (d, J = 11.5 Hz, 1 H),
7.95 (s, 1 H), 7.47–7.39 (m, 2 H), 6.90–6.86 (m, 2 H), 3.77 (s, 3 H).
1H NMR (500 MHz, CDCl3):  (rotamer 2) = 8.30 (d, J = 1.9 Hz, 1 H),
7.31 (s, 1 H), 7.06–6.97 (m, 2 H), 6.86–6.82 (m, 2 H), 3.79 (s, 3 H).
13C NMR (126 MHz, CDCl3):  (mixture of rotamers) = 163.0, 158.8,
157.6, 156.7, 129.9, 129.5, 121.8, 121.7, 114.9, 114.2, 55.5, 55.4.
HRMS (ESI+): m/z [M + H]+ calcd for C8H10NO2: 152.07060; found:
152.07045.
N-[4-(Trifluoromethoxy)phenyl]formamide (3h)20p
Obtained as a 1.5:1 mixture of two rotamers.
Yield: 426 mg (97%); yellow oil.
N-[4-(tert-Butyl)phenyl]formamide (3d)29
Obtained as a 1.2:1 mixture of two rotamers.
Yield: 297 mg (78%); white solid; mp 63.1–65.5 °C.
1H NMR (500 MHz, CDCl3):  (major rotamer) = 8.65 (d, J = 11.5 Hz, 1
H), 7.37–7.33 (m, 2 H), 7.02 (s, 2 H), 1.31 (s, 9 H).
1H NMR (500 MHz, CDCl3):  (minor rotamer) = 8.36 (s, 1 H), 7.45 (s, 2
H), 7.32 (dd, J = 8.8, 1.4 Hz, 2 H), 1.30 (s, 9 H).
13C NMR (126 MHz, CDCl3):  (mixture of rotamers) = 162.8, 158.9,
148.5, 147.9, 134.2, 134.1, 126.6, 125.9, 119.9, 118.9, 34.4, 34.4, 31.3,
31.2.
1H NMR (500 MHz, CDCl3):  (major rotamer) = 8.37 (d, J = 1.3 Hz, 1
H), 7.89 (s, 1 H), 7.61–7.55 (m, 2 H), 7.17 (d, J = 8.6 Hz, 2 H).
1H NMR (500 MHz, CDCl3):  (minor rotamer) = 8.79 (s, 1 H), 8.67 (d,
J = 11.2 Hz, 1 H), 7.22 (d, J = 8.6 Hz, 2 H), 7.15–7.11 (m, 2 H).
13C NMR (126 MHz, CDCl3):  (mixture of rotamers) = 162.7, 159.2,
146.4, 145.6, 135.5, 135.4, 120.4 (q, J = 257.0 Hz), 120.3 (q, J = 257.0
Hz), 122.5, 121.8, 121.2, 120.0.
HRMS (ESI–): m/z [M – H]+ calcd for C8H5F3NO2: 204.02779; found:
204.02719.
N-(4-Cyanophenyl)formamide (3i)21
HRMS (ESI+): m/z [M + H]+ calcd for C11H16NO: 178.12264; found:
178.12245.
Obtained as a 3:1 mixture of two rotamers.
Yield: 278 mg (88%); white solid; mp 190.3–191.6 °C.
N-(4-Fluorophenyl)formamide (3e)28
1H NMR (500 MHz, DMSO-d6):  (major rotamer) = 10.63 (s, 1 H),
7.80–7.75 (m, 4 H), 7.38 (d, J = 8.3 Hz, 1 H).
1H NMR (500 MHz, DMSO-d6):  (minor rotamer) = 10.51 (s, 1 H), 8.99
Obtained as a 1:1 mixture of two rotamers.
Yield: 271 mg (90%); yellow solid; mp 67.5–69.8 °C.
(s, 1 H), 8.37 (s, 4 H).
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Synthesis
13C NMR (126 MHz, DMSO-d6):  (mixture of rotamers) = 163.2,
160.9, 143.4, 142.8, 134.3, 133.9, 119.8, 119.4, 117.5, 105.9, 105.7.
HRMS (ESI+): m/z [M + Na]+ calcd for C8H6N2NaO: 169.03723; found:
169.03708.
1H NMR (500 MHz, CDCl3):  (minor rotamer) = 8.44 (d, J = 1.8 Hz, 1
H), 7.83 (d, J = 8.4 Hz, 1 H), 7.39 (d, J = 2.3 Hz, 1 H), 7.11 (br s, 1 H),
7.01 (d, J = 8.4 Hz, 1 H), 2.26 (s, 3 H).
13C NMR (126 MHz, CDCl3):  (1.1:1 mixture of rotamers) = 162.9,
158.9, 134.1, 134.0, 133.7, 133.3, 131.8, 130.5, 130.1, 129.9, 124.3,
122.0, 119.1, 118.3, 17.6, 17.5.
N-m-Tolylformamide (3j)28
HRMS (ESI–): m/z [M – H]+ calcd for C8H7BrNO: 211.97165; found:
Obtained as a 1.3:1 mixture of two rotamers.
211.97118.
Yield: 250 mg (86%); yellow oil.
1H NMR (500 MHz, CDCl3):  (major rotamer) = 8.67 (d, J = 11.3 Hz, 1
H), 8.42 (br s, 1 H), 7.24–7.15 (m, 2 H), 6.90–6.86 (m, 2 H), 2.35 (s, 3
H).
1H NMR (500 MHz, CDCl3):  (minor rotamer) = 8.33 (d, J = 1.9 Hz, 1
H), 7.47–7.44 (m, 1 H), 7.38 (d, J = 2.0 Hz, 1 H), 7.30 (s, 1 H), 6.98 (d, J =
16.8 Hz, 1 H), 6.93 (d, J = 19.2 Hz, 1 H), 2.33 (s, 3 H).
N-([1,1′-Biphenyl]-4-yl)formamide (3n)20q
Obtained as a 1.1:1 mixture of two rotamers.
Yield: 318 mg (75%); white solid; mp 170.9–172.4 °C.
1H NMR (500 MHz, CDCl3):  (major rotamer) = 8.42 (d, J = 1.8 Hz, 1
H), 7.63 (d, J = 2.1 Hz, 1 H), 7.59–7.54 (m, 7 H), 7.38–7.31 (m, 2 H).
13C NMR (126 MHz, CDCl3):  (mixture of rotamers) = 162.8, 159.1,
139.8, 139.0, 136.8, 136.6, 129.5, 128.9, 126.0, 125.6, 120.6, 119.5,
117.0, 115.7, 21.4, 21.3.
HRMS (ESI+): m/z [M + Na]+ calcd for C8H9NONa: 158.05764; found:
158.05750.
1H NMR (500 MHz, CDCl3):  (minor rotamer) = 8.73 (d, J = 11.4 Hz, 1
H), 7.62–7.59 (m, 2 H), 7.46–7.42 (m, 4 H), 7.20–7.11 (m, 3 H).
13C NMR (126 MHz, CDCl3):  (1.1:1 mixture of rotamers) = 162.4,
158.9, 140.3, 140.0, 138.4, 137.7, 136.1, 135.8, 128.9, 128.8, 128.4,
127.7, 127.4, 127.2, 126.8, 126.8, 120.3, 119.1.
HRMS (ESI+): m/z [M + H]+ calcd for C13H12NO: 198.09134; found:
198.09119.
N-o-Tolylformamide (3k)20q
Obtained as a 2:1 mixture of two rotamers.
N-(4-Phenoxyphenyl)formamide (3o)30
Yield: 232 mg (80%); white solid; mp 170.9–172.4 °C.
Obtained as a 1:1 mixture of two rotamers.
1H NMR (500 MHz, CDCl3):  (major rotamer) = 8.54 (d, J = 11.3 Hz, 1
H), 7.70 (s, 1 H), 7.18 (d, J = 13.6 Hz, 2 H), 7.15–7.10 (m, 2 H), 2.29 (s, 3
Yield: 394 mg (86%); light yellow solid; mp 89.2–92.3 °C.
H).
1H NMR (500 MHz, CDCl3):  (rotamer 1) = 8.62 (d, J = 11.4 Hz, 1 H),
8.37 (br s, 1 H), 7.53–7.49 (m, 1 H), 7.39–7.29 (m, 2 H), 7.17–7.05 (m,
2 H), 7.04–6.93 (m, 4 H).
1H NMR (500 MHz, CDCl3):  (rotamer 2) = 8.35 (d, J = 1.9 Hz, 1 H),
7.58 (br s, 1 H), 7.53–7.49 (m, 1 H), 7.39-7.29 (m, 2 H), 7.17–7.05 (m, 2
H), 7.04–6.93 (m, 4 H).
13C NMR (126 MHz, CDCl3):  (mixture of rotamers) = 162.9, 159.0,
157.3, 157.1, 154.9, 153.9, 132.2, 131.9, 129.8, 129.7, 123.5, 123.2,
121.7, 121.1, 120.1, 119.5, 118.7, 118.5.
1H NMR (500 MHz, CDCl3):  (minor rotamer) = 8.42 (d, J = 1.9 Hz, 1
H), 7.90 (s, 1 H), 7.21 (d, J = 7.5 Hz, 2 H), 7.09 (d, J = 7.6 Hz, 2 H), 2.26
(s, 3 H).
13C NMR (126 MHz, CDCl3):  (2:1 mixture of rotamers) = 163.1,
159.0, 134.9, 134.6, 131.2, 130.5, 129.5, 128.4, 127.1, 126.9, 126.0,
125.5, 123.0, 120.6, 17.7, 17.6.
HRMS (ESI+): m/z [M + H]+ calcd for C8H10NO: 136.07569; found:
136.07556.
HRMS (ESI+): m/z [M + H]+ calcd for C13H12NO2: 214.08626; found:
214.08640.
N-(4-Bromo-3-methylphenyl)formamide (3l)
Obtained as a 1:1 mixture of two rotamers.
Yield: 420 mg (84%); gray solid; mp 86.5–87.8 °C.
1H NMR (500 MHz, CDCl3):  (rotamer 1) = 8.82 (d, J = 11.3 Hz, 1 H),
8.34 (d, J = 1.9 Hz, 1 H), 7.49–7.45 (m, 2 H), 7.22 (dd, J = 8.6, 2.7 Hz, 1
H), 2.38 (s, 3 H).
1H NMR (500 MHz, CDCl3):  (rotamer 2) = 8.65 (d, J = 11.3 Hz, 1 H),
7.82 (br s, 1 H), 7.43 (d, J = 8.6 Hz, 1 H), 6.96 (d, J = 2.7 Hz, 1 H), 6.80
(dd, J = 8.5, 2.7 Hz, 1 H), 2.35 (s, 3 H).
13C NMR (126 MHz, CDCl3):  (mixture of rotamers) = 162.8, 159.3,
139.6, 138.8, 136.1, 136.0, 133.4, 132.7, 122.2, 121.0, 120.8, 120.0,
119.0, 117.5, 23.0.
N-[4-(Phenylamino)phenyl]formamide (3p)31
Obtained as a 3:1 mixture of two rotamers.
Yield: 355 mg (78%); white solid; mp 172.0–173.3 °C.
1H NMR (500 MHz, DMSO-d6):  (major rotamer) = 9.97 (s, 1 H), 8.19
(d, J = 1.6 Hz, 1 H), 7.20 (t, J = 7.8 Hz, 3 H), 7.08–7.00 (m, 6 H).
1H NMR (500 MHz, DMSO-d6):  (minor rotamer) = 9.92 (d, J = 11.1
Hz, 1 H), 8.60 (d, J = 11.1 Hz, 1 H), 8.03 (s, 2 H), 7.46 (d, J = 8.8 Hz, 4 H),
6.77 (t, J = 7.3 Hz, 3 H).
13C NMR (126 MHz, DMSO-d6):  (3:1 mixture of rotamers) = 162.9,
159.4, 144.4, 144.3, 140.1, 139.6, 131.6, 131.3, 129.6, 129.6, 120.9,
120.0, 119.6, 119.6, 118.9, 118.2, 116.4, 116.3.
HRMS (ESI–): m/z [M – H]+ calcd for C8H7BrNO: 211.97165; found:
211.97118.
HRMS (ESI+): m/z [M + H]+ calcd for C13H13N2O: 213.10224; found:
213.10204.
N-(4-Bromo-2-methylphenyl)formamide (3m)22
Obtained as a 1.1:1 mixture of two rotamers.
N-(Pyridin-2-yl)formamide (3q)28
Yield: 300 mg (65%); white solid; mp 144.1–145.3 °C.
Obtained as a 1:1 mixture of two rotamers.
Yield: 187 mg (71%); yellow solid; mp 74.1–75.2 °C.
1H NMR (500 MHz, CDCl3):  (major rotamer) = 8.50 (d, J = 11.2 Hz, 1
H), 7.86 (br s, 1 H), 7.34 (d, J = 2.4 Hz, 2 H), 7.33 (dd, J = 5.2, 2.4 Hz, 1
H), 2.28 (s, 3 H).
© 2020. Thieme. All rights reserved. Synthesis 2020, 52, A–I

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Synthesis
1H NMR (500 MHz, CDCl3):  (rotamer 1) = 9.76 (s, 1 H), 8.52 (s, 1 H),
8.35–8.29 (m, 2 H), 7.78–7.72 (m, 1 H), 6.91 (d, J = 8.2 Hz, 1 H).
1H NMR (500 MHz, CDCl3):  = 7.50 (d, J = 7.8 Hz, 2 H), 7.31 (t, J = 7.7
Hz, 2 H), 7.10 (t, J = 7.3 Hz, 1 H), 2.16 (s, 3 H).
1H NMR (500 MHz, CDCl3):  (rotamer 2) = 9.56 (s, 1 H), 9.32 (d, J =
10.6 Hz, 1 H), 8.24 (d, J = 8.4 Hz, 1 H), 7.70–7.63 (m, 1 H), 7.10–7.05
(m, 2 H).
13C NMR (126 MHz, CDCl3):  = 168.5, 137.9, 129.0, 124.3, 120.0, 24.6.
HRMS (ESI+): m/z [M + H]+ calcd for C8H10NO: 136.07569; found:
136.07556.
13C NMR (126 MHz, CDCl3):  (mixture of rotamers) = 162.9, 159.4,
N-Phenylbutyramide (3v)33
151.0, 150.9, 148.6, 147.5, 138.8, 138.7, 120.2, 119.9, 115.1, 110.5.
HRMS (ESI+): m/z [M + H]+ calcd for C6H7N2O: 123.05529; found:
Yield: 284 mg (81%); yellow solid; mp 92.4–93.9 °C.
123.05518.
1H NMR (500 MHz, CDCl3):  = 7.52 (s, 1 H), 7.50 (s, 1 H), 7.32 (t, J = 7.9
Hz, 2 H), 7.10 (t, J = 7.3 Hz, 2 H), 2.34 (t, J = 7.4 Hz, 2 H), 1.77 (q, J = 7.4
Hz, 2 H), 1.02 (t, J = 7.4 Hz, 3 H).
N-(Quinolin-8-yl)formamide (3r)22
Obtained as a 4:1 mixture of two rotamers.
13C NMR (126 MHz, CDCl3):  = 171.3, 137.9, 129.0, 124.2, 119.8, 39.7,
Yield: 265 mg (71%); white solid; mp 151.9–152.5 °C.
19.0, 13.7.
1H NMR (500 MHz, CDCl3):  (major rotamer) = 9.79 (s, 1 H), 8.82 (dd,
J = 4.2, 1.6 Hz, 1 H), 8.77–8.73 (m, 1 H), 8.70 (d, J = 1.4 Hz, 1 H), 8.18
(dd, J = 8.3, 1.6 Hz, 1 H), 7.58–7.52 (m, 2 H), 7.48–7.46 (m, 1 H).
HRMS (ESI+): m/z [M + H]+ calcd for C10H14NO: 164.10699; found:
164.10671.
N-Phenyldecanamide (3w)20n
1H NMR (500 MHz, CDCl3):  (minor rotamer) = 9.46 (s, 1 H), 9.13 (d,
J = 11.7 Hz, 1 H), 8.82 (dd, J = 4.2, 1.6 Hz, 1 H), 8.77–8.73 (m, 1 H), 8.18
(dd, J = 8.3, 1.6 Hz, 1 H), 7.58–7.52 (m, 2 H), 7.48–7.46 (m, 1 H).
13C NMR (126 MHz, CDCl3):  (mixture of rotamers) = 160.6, 159.2,
149.0, 148.4, 138.3, 138.1, 136.4, 136.1, 133.5, 127.9, 127.3, 126.6,
122.5, 122.2, 121.7, 117.6, 111.0.
Yield: 383 mg (72%); light yellow solid; mp 65.2–65.9 °C.
1H NMR (500 MHz, CDCl3):  = 7.51 (d, J = 7.8 Hz, 2 H), 7.31 (t, J = 7.7
Hz, 2 H), 7.22 (s, 1 H), 7.09 (t, J = 7.3 Hz, 1 H), 2.35 (t, J = 7.5 Hz, 2 H),
1.74–1.72 (m, 2 H), 1.69–1.32 (m, 12 H), 0.88 (t, J = 6.8 Hz, 3 H).
13C NMR (126 MHz, CDCl3):  = 171.4, 138.0, 129.0, 124.2, 119.8, 37.9,
31.9, 29.4, 29.4, 29.3, 29.3, 25.7, 22.7, 14.1.
HRMS (ESI+): m/z [M + H]+ calcd for C10H9N2O: 173.07094; found:
173.07077.
HRMS (ESI+): m/z [M + H]+ calcd . for C16H26NO+ [M+H]+: 248.20089;
found: 248.20067.
N-Phenethylformamide (3s)20q
Obtained as a 5:1 mixture of two rotamers.
Funding Information
Yield: 261 mg (81%); colorless oil.
1H NMR (500 MHz, CDCl3):  (major rotamer) = 8.09 (d, J = 1.8 Hz, 1
H), 7.31–7.29 (m, 2 H), 7.26–7.22 (m, 1 H), 7.21–7.18 (m, 2 H), 5.81 (s,
1 H), 3.56 (q, J = 6.7 Hz, 2 H), 2.83 (t, J = 6.9 Hz, 2 H).
1H NMR (500 MHz, CDCl3):  (minor rotamer) = 7.87 (d, J = 12.0 Hz, 1
H), 7.33–7.31 (m, 2 H), 7.22–7.21 (m, 1 H), 7.18–7.14 (m, 2 H), 5.28 (s,
1 H), 3.45 (q, J = 6.8 Hz, 2 H), 2.80 (d, J = 6.8 Hz, 2 H).
13C NMR (126 MHz, CDCl3):  (mixture of rotamers) = 164.7, 161.3,
138.4, 137.5, 128.8, 128.7, 128.6, 126.8, 126.6, 43.2, 39.1, 37.6, 35.4.
HRMS (ESI+): m/z [M + H]+ calcd for C9H12NO: 150.09134; found:
150.09116.
This research was supported by the National Natural Science Founda-
tion of China (Grant No. 21502062), the Scientific Research Program
Guiding Project of Hubei Provincial Department of Education (Grant
No. B2019135), the Teachers’ Scientific Research Ability Cultivation
Fund, Hubei University of Arts and Science (Natural Science, Grant
No. 2018kypy001), the Foundation of Hubei University of Arts and
Science (Grant No. 2059057), the Open Foundation of Discipline of
Hubei University of Arts and Science (Grant Nos. XK2019038,
XK2019039), and the National Natural Science Foundation Cultivation
Project of Hubei University of Arts and Science (Grant No. 2019ky-
pygp003).NationalNatural
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N-Hexylformamide (3t)32
Obtained as a 3.7:1 mixture of two rotamers.
Supporting Information
Yield: 261 mg (94%); colorless oil.
Supporting information for this article is available online at
1H NMR (500 MHz, CDCl3):  (major rotamer) = 8.13 (d, J = 1.8 Hz, 1
H), 5.84 (s, 1 H), 3.26 (q, J = 6.8 Hz, 2 H), 1.50 (d, J = 7.1 Hz, 2 H), 1.30–
1.23 (m, 6 H), 0.89–0.86 (m, 3 H).
https://doi.org/10.1055/s-0040-1705892. Su
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1H NMR (500 MHz, CDCl3):  (minor rotamer) = 8.00 (d, J = 12.0 Hz, 1
H), 5.28 (s, 1 H), 3.18 (q, J = 6.8 Hz, 2 H), 1.47 (s, 2 H), 1.35–1.30 (m, 6
H), 0.85 (d, J = 3.0 Hz, 3 H).
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© 2020. Thieme. All rights reserved. Synthesis 2020, 52, A–I

I
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© 2020. Thieme. All rights reserved. Synthesis 2020, 52, A–I