Cobalt(II)-Catalyzed N-Acylation of Amines through a Transamidation Reaction

Article abstract of DOI:10.1002/ejoc.201800253

A practical protocol has been developed for a Co(OAc)₂·4H₂O-catalyzed transamidation reaction. The reaction gives high yields and uses N,N-dimethylformamide and other amides as carbonyl sources. The protocol is rapid and simple, and it does not require any acids, bases, ligands, or other additives. It works well for a wide range of primary, secondary, and heterocyclic amines.

Full text of DOI:10.1002/ejoc.201800253

A Journal of
Accepted Article
Title: Cobalt (II)-Catalyzed N-Acylation of Amines via Transamidation
Reaction
Authors: Juan Ma, Feng Zhang, Jingyu Zhang, and Hang Gong
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To be cited as: Eur. J. Org. Chem. 10.1002/ejoc.201800253
Link to VoR: http://dx.doi.org/10.1002/ejoc.201800253
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European Journal of Organic Chemistry
10.1002/ejoc.201800253
Full Article
DOI: 10.1002/adsc.201((will be filled in by the editorial staff))
Cobalt (II)-Catalyzed N-Acylation of Amines via
Transamidation Reaction
†
‡
†
,†
Juan Ma, Feng Zhang, Jingyu Zhang, Hang Gong*
†The Key Laboratory for Green Organic Synthesis and Application of Hunan Province; The Key Laboratory of
Environmentally Friendly Chemistry and Application of the Ministry of Education College of Chemistry, Xiangtan
University, Xiangtan 411105 (China). Fax: (+86)-731-5829-2251; phone: (+86)-731-5829-2251; e-mail:
hgong@xtu.edu.cn Homepage http://yjs.xtu.edu.cn/gmis/dsgl/dsfc.aspx?id=9978A402D577F13438429E6FC6B2EF33
‡
College of Science, Hunan Agricultural University, Changsha, 410128, (China)
Received: ((will be filled in by the editorial staff))
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201######.((Please
delete if not appropriate))
Abstract. A practical protocol has been developed here for widely served as the source of −NMe , −CHO, −CO,
2
[8]
the Co(OAc)
high yields using N,N-dimethylformamide and other
amides as carbonyl sources. The protocol is simple, does reported using DMF as a carbonyl source in the
2
•4H
2
O-catalyzed transamidation reaction with −CONMe
2
, and −Me.
Numerous N-acylation of amines have been
[9]
[3a]
not require any acid, base, ligand, or other additives, time- presence of various catalysts, such as Pd, Ni,
[
3g]
[3d]
[3l]
[3m]
[3c]
saving, and encompasses a broad substrate scope for
primary, secondary, and heterocyclic amines.
Fe, Ce, Cu, L-Proline,
boronic acid and
[3b,f]
[10]
[3j]
its derivatives,
imidazole and its derivatives.
Particularly, the transamidation reaction also can be
achieved in mild conditions by using hydroxylamine
Keywords: N-Acylation, Transamidation, Cobalt, Amide
[3k]
hydrochloride as an inorganic catalyst.
Herein, highly efficient Co(OAc)
a
2
•4H O-
2
catalyzed strategy for N-acylation of amines using
DMF and other amides as carbonyl sources is
reported (Scheme 1). This strategy is simple and cost-
effective because the reagents and catalyst are
inexpensive and do not require any acid, base, ligand,
or other additives. A broad substrate scope is given,
and primary, secondary, and heterocyclic amines with
various functional groups can be converted to the
desired N-acylation product with good to excellent
yields. This strategy is time-saving, the reaction could
be completed within 3 hours. Furthermore, other
amides such as formamide, N-methylformamide,
acetamide and propionamide can also serve as
carbonyl sources to achieve the N-acylation reaction
with excellent yields.
N-acylation of amines is a very important organic
reaction.[ Moreover, the amide building block is
widely present in pharmaceuticals, such as
1]
[2a]
[2b]
[2c]
formoterol,
leucovorin,[
lacosamide,
tetrahydrolipstatin,
2d]
[2e]
natural products,
and functional
materials (Figure 1).[
2f]
Several carbonyl sources, such as N,N-
dimethylformamide (DMF)/N,N-dimethylacetamide
3]
[4]
[5]
[6]
(
DMA),[ formic acid/formate, methanol, ester,
[7]
and others have been applied to the N-acylation of
amines. Among them, DMF is widely used as an
inexpensive and readily available solvent in industrial
production and laboratory research. And DMF also
Initially, the reaction of tetrahydroisoquinoline and
DMF in the presence of CoCl was selected as the
2
model reaction (Table 1). Various reaction conditions
were confirmed, including the type and the amount of
Co catalyst, reaction temperature, reaction time, and
the reaction atmosphere. The results indicated that the
conversion rate is very poor in the absence of Co
catalyst (entry 1). When CoCl (20 mol%) and
2
Figure 1. Amide-containing biologically active molecular
and polymer.
Scheme 1. Co-catalyzed N-acylation of amines via
transamidation reaction.
1
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European Journal of Organic Chemistry
10.1002/ejoc.201800253
Table 1. Selected optimization results.a
Table 2. Substrate scope of amines.a
T
t
Yield
(%)
27
91
44
Entry
[Co](equiv)
--
(oC) (h)
150 18
150 18
150 18
150 18
150 18
1
2
3
4
5
CoCl
CoSO
2
(0.2)
(0.2)
4
Co(acac)
Co(acac)
2
(0.2)
(0.2)
75
63
3
cobaltous
naphthenate(0.2)
6
150 18
84
7
8
9
Co(OAc)
Co(OAc)
Co(OAc)
2
·4H
·4H
·4H
2
O(0.2) 150 18
O(0.15) 150 18
O(0.1) 150 18
O(0.05) 150 18
O(0.01) 150 18
O(0.15) 140 18
O(0.15) 130 18
O(0.15) 110 18
97
98
92
82
82
86
81
56
99
2
2
2
2
1
1
1
1
1
1
1
1
1
0
1
2
3
4
5
6
7
8
Co(OAc)
Co(OAc)
Co(OAc)
Co(OAc)
Co(OAc)
Co(OAc)
Co(OAc)
Co(OAc)
Co(OAc)
Co(OAc)
2
·4H
·4H
·4H
·4H
·4H
·4H
·4H
·4H
·4H
·4H
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
O(0.15) 150
O(0.15) 150
O(0.15) 150
O(0.15) 150
O(0.15) 150
4
3
2
1
3
3
3
3
3
3
3
a
b
Unless otherwise noted, all reactions were conducted on a
.2 mmol scale, DMF (1.0 mL), Co(OAc) ·4H O (15
100(99)
91
0
2
2
mol%) in a sealed tube under an atmosphere of argon for 3
77
59
86
82
75
82
16
12
b
h. Isolated yield was given; Absence of catalyst.
c
19
2
2
2
2
0
1
2
3
Fe(OAc)
Mn(OAc)
2
·4H
·2H
2
O(0.15) 150
O(0.15) 150
150
O(0.15) 150
amines, such as primary, secondary, and heterocyclic
amines, using DMF as reagent was conducted (Table
3
2
Cu(OAc)
Ni(OAc) ·4H
2
2
). The reaction proceeded well when using
2
2
tetrahydroisoquinoline or its analogs as secondary
amine substrates; good to excellent yields were
obtained (2a–f). Different functional groups on the
benzene ring such as methoxy, bromide, and nitro
were compatible with this reaction. However, the
nitro group, which is known as an electron-
withdrawing group, has a negative influence on this
transformation (2d), and a yield of only 75% could be
obtained. When using heterocyclic amines as
substrates, excellent yields also could be achieved
d
24
Co(OAc)
Co(OAc)
2
2
·4H
·4H
2
O(0.15) 150
O(0.15) 150
e
25
2
a
Unless otherwise noted, all reactions were conducted at
0
.2 mmol scale in a sealed tube in 1.0 mL DMF under
1
argon atmosphere. Yields are detected by H NMR using
CH
as internal standard; Isolated yield; c Under air
b
3
NO
2
d
atmosphere; 1 mL toluene and 1.5 equiv. DMF were used;
e
1
mL dioxane and 1.5 equiv. DMF were used.
(
2g–h). Other secondary amines, including
Co(OAc)
2
·4H O(20 mol%) were used as catalyst, an
2
circularand linear amines, smoothly underwent the
transformation with good to excellent yields in most
cases (2i–o). In particular, N-formyl fluoxetine (2o),
excellent yield of 91% and 97% can be achieved,
respectively (entries 2, 7). A high yield of 82% still
can be achieved when the amount of Co(OAc)
2
·4H
2
O
[11]
which has been applied as a marker for fluoxetine,
reduced to 1 mol% (entries 8-11). Decreasing the
reaction temperature (entries 12-14) proved to be
unfavorable to this transformation. This reaction
proceeds quickly and can be completed within 3
hours (entries 15-18). Additionally, the presence of
air is harmful to this reaction (entry 19). Afterward,
could be obtained with good yield (84%). However,
the ethyl substitution on nitrogen resulted in obvious
steric hindrance and subsequent lower yields (58%)
(
2j). This successful protocol for N-formylation of
secondary amines were expanded to primary amines,
and a high efficiency as well as secondary amines
were obtained (2p–v). Remarkably, the substrates
with hydroxyl also proceeded this reaction smoothly
acetate-containing
metal
salts,
2
such
as
Fe(OAc)
Ni(OAc)
2
·4H
·4H
2
O, Mn(OAc)
3
·2H O, Cu(OAc)
2
and
2
2
O were investigated as catalyst. And
(
2u). The N-formylation of primary amine is a
good yields also could be achieved (entries 20-23).
Finally, this reaction was conducted by using
stoichiometric amounts of DMF (1.5 euive.) as
reagent in other solvent, only poor yield could be
found (entries 24-25).
valuable organic reaction. For instance, the natural
molecule homoveratrylamine can be converted to N-
formylation product 2x, which can then be applied as
a precursor for preparing the natural products
pseudopalmatine,
8-oxopseudopalmatine,
and
After optimization, N-formylation of various
[12]
ilicifoline B.
2
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European Journal of Organic Chemistry
10.1002/ejoc.201800253
Table 3. Substrate scope of amides.a
Scheme 2. Gram reaction, competition experiment and
radical inhibition experiments.
achieved at an excellent yield of 94% and 85%,
respectively (entries 3-4). However, when aromatic
amides such as 2-thiophenecarboxamide and
benzamide were used as carbonyl sources, only 38%
and 32% yield could be obtained, respectively
a
Unless otherwise noted, all reactions were conducted on a
0
.2 mmol scale in a sealed tube in 1.0 mL amide under an
b
atmosphere of argon for 3 h. Isolated yield was given;
From 2-thiophenecarboxamide 0.5 g, ethylene glycol 0.5
mL, reaction time is 24 h; From benzamide 0.5 g,
c
(
entries 5-6).
ethylene glycol 0.5 mL, reaction time is 24 h.
Since the N-acetylation and N-propionylation of 1a
achieved with good results, the extrapolation for the
N-acylation and N-propionylation of several amines
were conducted (Table 4). Delightedly, both the
primary and secondary amine are transferred to
desired products with satisfied yields (2za-zb, ze-zn).
Importantly, the gram-scale reaction of
tetrahydroisoquinoline 1a and 1q using only 3 mol%
To validate the practicability of the strategy, the
extrapolation
for
the
N-acylation
of
tetrahydroisoquinoline using various carbonyl
sources was conducted (Table 3). The results
indicated that formamide and N-methylformamide,
can also serve as formyl sources to achieve the N-
formylation reaction with excellent yields (entries 1-
). When acetamide and propionamide were used, the
N-acetylation and N-propionylation product were
Co(OAc)
2
•4H
2
O as catalyst were conducted (Scheme
2
2
, A), and an excellent yield of 86% and 89% were
achieved with an extended reaction time (24 h)
respectively. The competition experiment also was
conducted to investigate the selectivity of this
reaction, and the results indicate that the activation of
primary aliphatic amine is slightly higher than the
secondary aliphatic amine (Scheme 2, B). To
examine the reaction mechanism, radical inhibition
experiments were conducted using 1 equiv butylated
hydroxytoluene (BHT) or 1,1-diphenylethene as
blocker, resulting in the desired product with 96%
and 95% yield, respectively (Scheme 2, C). In our
opinion, this reaction is not a radical process, but
instead, is a nucleophilic process.
Table 4. Substrate scope of acetylation and propanylation
of amine.a
Based on the radical inhibition experiments and the
3a
reported metal-catalyzed N-formylation reactions, a
reasonable mechanism is proposed (Scheme 3). First,
the carbonyl of DMF is activated by Co(OAc) via
2
coordination. Subsequently, the activated DMF
undergoes nucleophilic attack by the amine, which
results in the formation of a tetrahedral intermediate
(
I). Afterward, with a proton transfer, the sterically
congested intermediate (I) disintegrates, resulting in
intermediate II. Finally, the target molecule (T.M.) in
intermediate II is replaced by DMF to finish the
catalyzed cycle.
a
Unless otherwise noted, all reactions were conducted on a
0
.2 mmol scale, acetamide or propionamide (1.0 g),
Co(OAc) ·4H O (15 mol%) in a sealed tube under an
atmosphere of argon for 3 h. Isolated yield was given.
2
2
3
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European Journal of Organic Chemistry
10.1002/ejoc.201800253
1
0
5
H), 4.63 (major rotamer, s, 1.27H), 4.49 (minor rotamer, s,
.77H), 3.79-3.75 (m, 3.89H), 3.63 (major rotamer, t, J =
13
.8 Hz, 1.25H), 2.90-2.83 (m, 2H); C NMR (100 MHz,
CDCl
3
) δ 161.68 (major rotamer), 161.22 (minor rotamer),
58.54 (minor rotamer), 158.19 (major rotamer), 135.74
minor rotamer), 134.80 (major rotamer), 127.68 (major
rotamer), 126.92 (minor rotamer), 124.40 (minor rotamer),
23.86 (major rotamer), 113.77 (minor rotamer), 113.58
1
(
1
(
major rotamer), 113.06 (major rotamer), 112.84 (minor
rotamer), 55.32 (s), 46.88 (minor rotamer), 43.20 (major
rotamer), 41.86 (major rotamer), 37.91 (minor rotamrer),
3
3
1
0.03 (major rotamer), 28.28 (minor rotamer); IR (neat)
140, 1672, 1612, 1508, 1402, 1312, 1277, 1262, 1241,
－
-
1
2
119, 1036 cm ; HRMS (ESI) m/z [M+HCO H-H] calcd
for C12
H
14NO
4
236.09173, found 236.09208.
-bromo-3,4-dihydroisoquinoline-2(1H)-carbaldehyde
2c): Purified by TLC; Yellow solid; Isolated yield 99%;
7
(
o
1
3
mp 58-60 C; H NMR (400 MHz, CDCl ) δ 8.24 (minor
rotamer, s, 0.36H), 8.19 (major rotamer, s, 0.64H), 7.33-
7.26 (m, 2H), 7.02 (t, J = 8.8 Hz, 1H), 4.66 (major rotamer,
s, 1.28H), 4.52 (minor rotamer, s, 0.72H), 3.78 (minor
rotamer, t, J = 6.2 Hz, 0.74H), 3.65 (major rotamer, t, J =
Scheme 3. Proposed mechanism for transamidation
reaction using Co(OAc) •4H O as catalyst.
2 2
13
5
.8 Hz, 1.33H), 2.87-2.80 (m, 2H); C NMR (100 MHz,
In summary, an efficient cobalt (II)-catalyzed N-
acylation of amines using DMF and other amides as
carbonyl sources was developed. The advantages of
this strategy are the use of a metal as the catalyst that
is readily available and inexpensive, the
unencumbered availability of various inexpensive
amides as the carbonyl source, the lack of
requirement for any acid, base, ligand, or other
additives, the time-saving process, broad substrate
scopes, and high yields.
CDCl
34.30 (minor rotamer), 133.92 (major rotamer), 133.40
3
) δ 161.70 (major rotamer), 161.16 (minor rotamer),
1
(
minor rotamer), 132.54 (major rotamer), 130.90 (minor
rotamer), 130.62 (major rotamer), 130.23 (minor rotamer),
129.83 (major rotamer), 129.48 (major rotamer), 128.84
(
minor rotamer), 120.31 (major rotamer), 119.99 (minor
rotamer), 46.91 (minor rotamer), 43.01 (major rotamer),
1.87 (major rotamer), 37.78 (minor rotamer), 29.29
major rotamer), 27.50 (minor rotamer); IR (neat) 3140,
4
(
-
1
1672, 1402, 1191, 1157, 1116, 1075, 1051, 932, 829 cm ;
+
HRMS (ESI) m/z [M+NH
4
]
calcd for C10
H
14BrN
2
O
2
7
57.0284, found 257.02746.
-nitro-3,4-dihydroisoquinoline-2(1H)-carbaldehyde
1
(
2d): Purified by TLC; brown oil; Isolated yield 75%; H
NMR (400 MHz, CDCl
3
) δ 8.29 (minor rotamer, s, 0.38H)
8
7
.24 (major rotamer, s, 0.62H), 8.07-8.03 (m, 2H), 7.36-
Experimental Section
.30 (m, 1H), 4.79 (major rotamer, s, 1.23H), 4.66 (minor
rotamer, s, 0.68H), 3.85 (minor rotamer, t, J = 6.2 Hz,
0.75H), 3.73 (major rotamer, t, J = 6.0 Hz, 1.18H), 3.05-
General Information
13
2
3
.97 (m, 2H); C NMR (100 MHz, CDCl ) δ 161.59
(
major rotamer), 161.07 (minor rotamer), 146.83 (major
rotamer), 146.55 (minor rotamer), 142.20 (minor rotamer),
41.17 (major rotamer), 133.77 (minor rotamer), 133.51
major rotamer), 130.38 (minor rotamer), 130.11 (major
rotamer), 122.14 (minor rotamer), 121.95 (major rotamer),
21.70 (major rotamer), 121.28 (minor rotamer), 47.06
minor rotamer), 42.49 (major rotamer), 42.06 (major
2 2
A solution of amine (0.2 mmol), and Co(OAc) ·4H O (15
mol%) in DMF (1 mL) was stirred in a sealed tube under
argon atmosphere at 150 °C for 3 h. After cooled to room
1
(
2
temperature, 5 mL H O was added. And then, the reaction
mixture was extracted with ethyl acetate (3 mL X 6).
Afterwards, the combined organic phase was dried with
1
(
2 4
Na SO , and the solvent was evaporated in vacuo. The
rotamer), 37.30 (minor rotamer), 29.95 (major rotamer),
residue was purified by preparative thin-layer
chromatography on silica gel with petroleum ether and
ethyl acetate to yield the pure product.
2
1
[
8.22 (minor rotamer); IR (neat) 3129, 1672, 1525, 1402,
-1
347, 1088, 855, 744 cm ; HRMS (ESI) m/z
－
M+CH
3
CO
65.08243.
-formyl-1,3-dihydro-isoindole (2e) : Purified by TLC;
2 13 2 5
H-H] calcd for C12H N O 265.0819, found
2
2
Experimental Data
[15]
1
Black oil; Isolated yield 84%; H NMR (400 MHz, CDCl
3
)
[
13]
2
-formyl-1,2,3,4-tetrahydroisoquinoline (2a) : Purified
δ 8.43 (s, 1H), 7.32-7.28 (m, 4H), 4.91 (s, 2H), 4.77(s,
1
13
by TLC; Yellow oil; Isolated yield 99%; H NMR (400
MHz, CDCl ) δ 8.22 (minor rotamer, s, 0.36H), 8.17
2H); C NMR (100 MHz, CDCl ) δ 161.56, 135.99,
3
3
135.34, 128.07, 127.76, 123.30, 122.88, 51.53, 49.92; IR
-
1
(
major rotamer, s, 0.64H), 7.20-7.10 (m, 4H), 4.67 (major
(neat) 3140, 1668, 1465, 1402, 1159, 1092, 747, 608 cm ;
－
rotamer, 1.27H), 4.52 (minor rotamer, 0.73H), 3.76 (minor
HRMS (ESI) m/z [M+Cl] calcd for C H ClNO 182.03672,
9
9
rotamer, t, J = 6.2 Hz, 0.77H), 3.63 (major rotamer, t, J =
found 182.03682.
1
3
5
.8 Hz, 1.27H), 2.90-2.83 (m, 2H); C NMR (100 MHz,
5-formyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridine
[3a]
CDCl
34.42 (minor rotamer), 133.60 (major rotamer), 132.29
minor rotamer), 131.76 (major rotamer), 129.21 (minor
rotamer), 128.97 (major rotamer), 127.12, 126.75-126.52
m), 125.94, 47.33 (minor rotamer), 43.26 (major rotamer),
2.31 (major rotamer), 38.01 (minor rotamer), 29.72
3
) δ 161.75 (major rotamer), 161.25 (minor rotamer),
( (2f) : Purified by TLC; Yellow oil; Isolated yield 97%;
1
1
(
H NMR (400 MHz, CDCl ) δ 8.25 (minor rotamer, s,
3
0.39H), 8.21 (major rotamer, s, 0.61H), 7.18-7.16 (m, 1H),
6.82-6.80 (m, 1H), 4.61 (major rotamer, s, 1.29H), 4.48
(minor rotamer, s, 0.74H), 3.87 (minor rotamer, t, J = 5.6
Hz, 0.74H), 3.71 (major rotamer, t, J = 5.8 Hz, 1.29H),
(
4
1
3
(
major rotamer), 27.94 (minor rotamer); IR (neat) 3151,
2.95-2.88 (m, 2H); C NMR (100 MHz, CDCl ) δ 161.81
3
3
1
7
025, 2931, 2862, 1672, 1584, 1498, 1439, 1400, 1343,
318, 1282, 1228, 1197, 1164, 1109, 1049, 930, 882, 814,
(major rotamer), 161.45 (minor rotamer), 133.93 (minor
rotamer), 132.22 (major rotamer), 130.85 (major rotamer),
130.77 (minor rotamer), 125.04 (major rotamer), 124.36
(minor rotamer), 123.88 (s), 45.82 (minor rotamer), 43.75
(major rotamer), 40.68 (major rotamer), 38.01 (minor
rotamer), 25.90 (major rotamer), 24.49 (minor rotamer); IR
(neat) 3129, 1705, 1670, 1433, 1402, 1314, 1176, 1043,
-
1
+
51, 710, 675, 606 cm ; HRMS (ESI) m/z [M+Na] calcd
for C10
H
11NNaO 184.07329, found 184.07325.
2
-formyl-l,2,3,4-tetrahydro-6-methoxyisoquinoline
[
14]
(
2b) : Purified by TLC; Yellow solid; Isolated yield
o
1
9
3
9%; mp 63-64 C; H NMR (400 MHz, CDCl ) δ 8.24
-
1
+
(
minor rotamer, s, 0.39H), 8.19 (major rotamer, s, 0.61H),
1018, 824, 706 cm ; HRMS (ESI) m/z [M+NH ] calcd
4
7
.06-7.01 (m, 1H), 6.80-6.76 (m, 1H), 6.67 (d, J = 10.0 Hz,
for C H N SO 185.07431, found 185.07353.
8
13
2
4
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European Journal of Organic Chemistry
10.1002/ejoc.201800253
[
16]
4
-phenylpiperazine-1-carboxaldehyde (2g) : Purified
(minor rotamer), 162.78 (major rotamer), 140.12 (major
rotamer), 139.92 (minor rotamer), 130.63 (major rotamer),
130.31 (minor rotamer), 130.12 (major rotamer), 129.80
(minor rotamer), 128.43 (major rotamer), 127.67 (minor
rotamer), 125.96 (minor rotamer, q, J = 3.7 Hz), 125.71
(major rotamer q, J = 3.7 Hz), 125.40 (major rotamer),
125.27 (minor rotamer), 122.69 (major rotamer), 122.57
(minor rotamer), 53.01 (minor rotamer), 47.43 (major
rotamer), 34.23 (major rotamer), 29.63 (minor rotamer)
o
by TLC; Yellow solid; Isolated yield 91%; mp 86-87 C;
1
H NMR (400 MHz, CDCl
3
) δ 8.08 (s, 1H), 7.31-7.27 (m,
2
=
H), 6.94-6.90 (m, 3H), 3.69 (t, J = 5.2 Hz, 2H), 3.51 (t, J
1
3
5.0 Hz, 2H), 3.18-3.12 (m, 4H); C NMR (100 MHz,
) δ 160.80, 150.99, 129.31, 120.88, 117.12, 50.50,
9.37, 45.57, 39.99; IR (neat) 3131, 1664, 1402, 1152,
CDCl
3
4
1
-
1
+
115, 529 cm ; HRMS (ESI) m/z [M+K] calcd for
KO 229.07377, found 229.07419.
C
11
H
14
N
2
[
17]
19
4
-phenylpiperidine-1-carbaldehyde (2h) : Purified by
; F NMR (377 MHz, CDCl3) δ -62.53 (major rotamer, s),
o
1
TLC; Yellow solid; Isolated yield 93%; mp 98-99 C; H
NMR (400 MHz, CDCl
-62.59 (minor rotamer, s); IR (neat) 3140, 2361, 2343,
3
) δ 8.07 (s, 1H), 7.34-7.18 (m, 5H), 1675, 1621, 1402, 1327, 1165, 1113, 1068, 1019, 848, 818
-
1
+
4
.57 (d, J = 13.6 Hz, 1H), 3.73 (d, J = 13.2 Hz, 1H), 3.20 (t, cm ; HRMS (ESI) m/z [M+NH
4
] calcd for C10
H
14
F
3
N
2
O
J = 13 Hz, 1H), 2.78-2.71 (m, 2H), 1.93 (t, J = 15.8 Hz,
235.10527, found 235.10666.
1
3
[19]
2
1
4
1
H), 1.65-1.58 (m, 2H); C NMR (100 MHz, CDCl
3
) δ
N-methyl-N-phenethyl-formamide (2m) : Purified by
1
60.92, 144.94, 128.68, 126.72, 126.67, 46.52, 42.94,
0.30, 33.95, 32.43; IR (neat) 3140, 1675, 1653, 1402,
TLC; Yellow oil; Isolated yield 95%; H NMR (400 MHz,
3
CDCl ) δ 8.01 (minor rotamer, s, 0.37H), 7.79 (major
-
1
+
170, 1064, 759, 699 cm ; HRMS (ESI) m/z [M+Na]
rotamer, s, 0.63H), 7.32-7.13 (m, 5H), 3.56 (minor rotamer,
calcd for C12
H
15NNaO 212.10459, found 212.10475.
t, J = 7.6 Hz, 0.82H), 3.47 (major rotamer, t, J = 7.0 Hz
[
7a]
13
N-methyl-N-benzylformamide (2i) : Purified by TLC;
1.24H), 2.90-2.82 (m, 5H); C NMR (100 MHz, CDCl
3
) δ
1
Yellow oil; Isolated yield 72%; H NMR (400 MHz,
162.71 (major rotamer), 162.54 (minor rotamer), 138.61
(minor rotamer), 137.76 (major rotamer), 128.82 (major
3
CDCl ) δ 8.29 (major rotamer, s, 0.57H), 8.17 (minor
rotamer, s, 0.42H), 7.38-7.20 (m, 5H), 4.53 (minor rotamer, rotamer), 128.79 (minor rotamer), 128.73 (major rotamer),
s, 0.84H), 4.40 (major rotamer, s, 1.13H), 2.85 (minor
128.60 (minor rotamer), 126.87 (major rotamer), 126.53
(minor rotamer), 51.32 (major rotamer), 46.05 (minor
rotamer), 35.14 (minor rotamer), 34.84 (major rotamer),
33.24 (minor rotamer), 29.80 (minor rotamrer); IR (neat)
13
rotamer, s, 1.38H), 2.79 (major rotamer, s, 1.80H);
NMR (100 MHz, CDCl ) δ 162.86 (major rotamer), 162.70
minor rotamer), 135.98 (minor rotamer), 135.72 (major
rotamer), 128.94 (major rotamer), 128.73 (minor rotamer),
28.28 (major rotamer), 128.15 (minor rotamer), 127.69
minor rotamer), 127.43 (major rotamer), 53.55 (major
C
3
(
-
1
3140, 1666, 1402, 1152, 529 cm ; HRMS (ESI) m/z
+
1
(
[M+H] calcd for C10
N-methyl-N-(naphthalen-1-ylmethyl)methanamide
(2n): Purified by TLC; Yellow oil; Isolated yield 95%; H
H13NO 164.10699, found 164.10706.
1
rotamer), 47.82 (minor rotamer), 34.13 (minor rotamer),
2
1
9.51 (major rotamer); IR (neat) 3122, 1664, 1402, 1379,
3
NMR (400 MHz, CDCl ) δ 8.38 (minor rotamer, s, 0.37H),
-
1
140, 1066, 1081, 705 cm ; HRMS (ESI) m/z
8.17 (major rotamer, s, 0.62H), 8.10 (d, J = 8.0 Hz, 0.56H),
7.91-7.82 (m, 2.32H), 7.55-7.26 (m, 4H), 4.98 (major
rotamer, s, 1.14H), 4.87 (minor rotamer, s, 0.72H), 2.85
－
[
M+CH
3
CO
08.09706.
2 3
H-H] calcd for C11H14NO 208.09682, found
2
[
18]
N-benzyl-N-ethylformamide (2j) : Purified by TLC;
(minor rotamer, s, 1.16H), 2.74 (major rotamer, s, 1.66H);
1
13
Yellow oil; Isolated yield 58%; H NMR (400 MHz,
3
C NMR (100 MHz, CDCl ) δ 163.31 (minor rotamer),
CDCl
3
) δ 8.25 (minor rotamer, s, 0.49H), 8.23 (major
162.38 (major rotamer), 133.87, 131.56, 131.32, 131.10,
rotamer, s, 0.52H), 7.39-7.21 (m, 5H), 4.55 (major rotamer, 131.02, 129.13, 128.94, 128.87, 128.72, 127.77, 126.76,
s, 1.02H), 4.40 (minor rotamer, s, 1.01H), 3.29 (minor
126.18, 125.57, 125.40, 125.15, 123.88 (major rotamer),
122.34 (minor rotamer), 51.05 (minor rotamer), 45.90
(major rotamer), 34.07 (major rotamer), 30.06 (minor
rotamer); IR (neat) 3140, 1672, 1510, 1402, 1258, 1161,
rotamer, q, J = 7.2 Hz, 1.01H), 3.21 (major rotamer, q, J =
7
1
.2 Hz, 1.05H), 1.15 (major rotamer, t, J = 7.2 Hz, 1.59H),
13
.06 (minor rotamer, t, J = 7.2 Hz, 1.51H); C NMR (100
) δ 162.67, 136.53 (major rotamer), 136.23
minor rotamer), 128.90 (minor rotamer), 128.70 (major
rotamer), 128.16 (major rotamer), 128.10 (minor rotamer),
27.59 (minor rotamer), 127.52 (major rotamer), 50.89
minor rotamer), 44.79 (major rotamer), 41.53 (major
-
1
+
MHz, CDCl
3
1081, 803, 779, 529 cm ; HRMS (ESI) m/z [M+H] calcd
(
for C13
H
14NO 200.10699, found 200.10687.
N-formylfluoxetine (2o): Purified by TLC; Yellow oil;
1
1
(
3
Isolated yield 84%; H NMR (400 MHz, CDCl ) δ 8.02
(minor rotamer, s, 0.41H), 7.99 (major rotamer, s, 0.59H),
7.44-7.26 (m, 7H), 6.90-6.87 (m, 2H), 5.20 (minor rotamer,
q, J = 4.4 Hz, 0.40H), 5.13 (major rotamer, dd, J = 8.8, 3.6
Hz, 0.60H), 3.58-3.52 (major rotamer, m, 1.49H), 3.42-
3.37 (minor rotamer, m, 0.62H), 2.93 (minor rotamer, s,
1.24H), 2.90 (major rotamer, s, 1.78H), 2.24-2.17 (m,
rotamer), 36.81 (minor rotamer), 14.39 (major rotamer),
1
1
2.25 (minor rotamer); IR (neat) 3140, 1672, 1497, 1402,
-1
109, 1079, 740, 703 cm ; HRMS (ESI) m/z
－
[
M+CH
3
CO
22.11189.
2 3
H-H] calcd for C12H16NO 222.11247, found
2
13
N-(4-methoxybenzyl)-N-methylformamide (2k): Purified
1.43H), 2.15-2.09 (m, 1.34H); C NMR (100 MHz,
CDCl ) δ 162.83 (major rotamer), 162.68 (minor rotamer),
1
by TLC; Yellow oil; Isolated yield 96%; H NMR (400
3
MHz, CDCl
(
(
3
) δ 8.27 (major rotamer, s, 0.58H), 8.13
160.23 (minor rotamer), 159.92 (major rotamer), 140.44
(minor rotamer), 139.92 (major rotamer), 129.10 (major
rotamer), 128.93 (minor rotamer), 128.33 (major rotamer),
128.10 (minor rotamer), 127.00-126.78 (m), 125.72 (minor
rotamer), 125.63 (major rotamer), 123.11 (s), 115.75
(minor rotamer), 115.66 (major rotamer), 78.17 (minor
rotamer), 76.94 (major rotamer), 46.04 (major rotamer),
41.57 (minor rotamer), 36.95 (major rotamer), 35.87
(minor rotamer), 34.93 (minor rotamer), 29.61 (major
minor rotamer, s, 0.42H), 7.20-7.12 (m, 2H), 6.91-6.85
m, 2H), 4.46 (minor rotamer, s, 0.87H), 4.33 (major
rotamer, s, 1.18H), 3.81 (major rotamer, s, 1.83H), 3.80
(
2
minor rotamer, s, 1.48H), 2.83 (minor rotamer, s, 1.29H),
1
3
.76 (major rotamer, s, 1.73H); C NMR (100 MHz,
) δ 162.62 (major rotamer), 162.53 (minor rotamer),
59.44 (major rotamer), 159.11 (minor rotamer), 130.48,
29.67 (minor rotamer), 128.80 (major rotamer), 128.13
CDCl
3
1
1
(
19
minor rotamer), 127.62 (major rotamer), 114.24 (major
rotamer); F NMR (377 MHz, CDCl3) δ -61.52 (minor
rotamer, s); -61.59 (major rotamer, s); IR (neat) 3140, 1675,
1616, 1519, 1329, 1251, 1161, 1113, 1068, 837, 703, 527
rotamer), 114.03 (minor rotamer), 113.65, 55.31 (major
rotamer, d, J = 4.4 Hz), 52.98 (minor rotamer), 47.12
-
1
+
(
major rotamer), 44.89 (minor rotamer), 33.95 (minor
cm ; HRMS (ESI) m/z [M+Na] calcd for C18
360.11818, found 360.11776.
18 3 2
H F NNaO
rotamer), 29.25 (major rotamer); IR (neat) 3140, 1671,
612, 1515, 1402, 1303, 1249, 1176, 1079, 1032, 846, 814
[
5c]
1
N-benzylformamide (2p) : Purified by TLC; Yellow
o 1
-
1
+
cm ; HRMS (ESI) m/z [M+NH
97.12845, found 197.13044.
N-methyl-N-[[4-
trifluoromethyl)phenyl]methyl]methanamide
4
] calcd for C10
H
17
N
2
O
2
solid; Isolated yield 86%; mp 54-58 C; H NMR (400
1
3
MHz, CDCl ) δ 8.25 (major rotamer, s, 0.84H), 8.17
(minor rotamer, d, J = 12 Hz, 0.16H), 7.35-7.24 (m, 5H),
6.00 (br s, 1H), 4.49 (major rotamer, d, J = 6.0 Hz, 1.71H),
(
(2l):
1
13
Purified by TLC; Yellow oil; Isolated yield 83%; H NMR
4.41 (minor rotamer, d, J = 6.4 Hz, 0.36H); C NMR (100
(
(
400 MHz, CDCl
3
) δ 8.31 (minor rotamer, s, 0.47H), 8.19
3
MHz, CDCl ) δ 164.77 (minor rotamer), 161.12 (major
major rotamer, s, 0.53H), 7.65-7.59 (m, 2H), 7.39-7.34 (m, rotamer), 137.56 (major rotamer), 137.47 (minor rotamer),
2
0
H), 4.58 (major rotamer, s, 1.11H), 4.48 (minor rotamer, s, 128.96 (minor rotamer), 128.82 (major rotamer), 128.01
.94H), 2.89 (major rotamer, s, 1.62H), 2.80 (minor
(minor rotamer), 127.83 (major rotamer), 127.73 (major
rotamer), 126.99 (minor rotamer), 45.69 (minor rotamer),
1
3
rotamer, s, 1.41H); C NMR (100 MHz, CDCl
3
) δ 162.86
5
This article is protected by copyright. All rights reserved.

European Journal of Organic Chemistry
10.1002/ejoc.201800253
[
7a]
4
2.19 (major rotamer); IR (neat) 3140, 1666, 1402, 699
N-(dodecyl)formamide (2v) : Purified by TLC; Gray
o 1
-
1
+
cm ; HRMS (ESI) m/z [M+H] calcd for C
8
H
10NO
solid; Isolated yield 95%; mp 33.2-34.5 C; H NMR (400
1
36.07569, found 136.07468.
3
MHz, CDCl ) δ 8.16 (major rotamer, s, 0.79H), 8.04
[
7a]
N-(2-phenylethyl)formamide (2q) : Purified by TLC;
(minor rotamer, d, J = 12 Hz, 0.20H), 5.62 (br s, 1H), 3.28
(major rotamer, q, J = 6.8 Hz, 1.62H), 3.21 (minor rotamer,
q, J = 6.8 Hz, 0.54H), 1.54-1.49 (m, 2H), 1.30-1.26 (m,
1
Yellow oil; Isolated yield 97%; H NMR (400 MHz,
3
CDCl ) δ 8.10 (major rotamer, s, 0.84H), 7.88 (minor
13
rotamer, d, J = 12 Hz, 0.16H), 7.34-7.17 (m, 5H), 5.82 (br
18H), 0.88 (t, J = 6.6 Hz, 3H); C NMR (100 MHz,
s, 1H), 3.59-3.54 (m, 1.68H), 3.49-3.44 (m, 0.39H), 2.86-
3
CDCl ) δ 164.73 (minor rotamer), 161.27 (major rotamer),
1
3
2
1
1
.80 (m, 2H); C NMR (100 MHz, CDCl
3
) δ 161.31,
41.85 (minor rotamer), 38.23 (major rotamer), 31.93
(major rotamer), 31.24 (minor rotamer), 29.64-29.16 (m),
26.87 (major rotamer), 26.40 (minor rotamer), 22.70,
38.53 (major rotamer), 137.62 (minor rotamer), 128.90-
28.74 (m), 126.95 (minor rotamer), 126.69 (major
-
1
rotamer), 43.20 (minor rotamer), 39.23 (major rotamer),
14.14; IR (neat) 3122, 1670, 1401, 1150, 1113, 529 cm ;
+
3
3
7.75 (minor rotamer), 35.51 (major rotamer); IR (neat)
HRMS (ESI) m/z [M+K] calcd for
13
C H27NKO
-
1
140, 1670, 1402, 1154, 689 cm ; HRMS (ESI) m/z
252.17242, found 252.17239.
+
[5c]
[
M+Na] calcd for
C
9
H
11NNaO 172.07329, found
N-formylhexamethyleneimine (2w) : Purified by TLC;
1
1
72.07409.
Yellow oil; Isolated yield 56%; H NMR (400 MHz,
[
5b]
N-formyl-3-phenylpropylamine (2r)
: Purified by
CDCl ) δ 8.08 (s, 1H), 3.48-3.37 (m, 4H), 1.74-1.58 (m,
3
1
13
TLC; Yellow oil; Isolated yield 98%; H NMR (400 MHz,
3
8H); C NMR (100 MHz, CDCl ) δ 162.93, 47.70, 43.43,
CDCl
3
) δ 8.13 (major rotamer, s, 0.80H), 7.99 (minor
30.27, 27.97, 26.97, 26.85; IR (neat) 3137, 2932, 2857,
1681, 1428, 1402, 1299, 1277, 1260, 1202, 1157, 1105,
rotamer, d, J = 12 Hz, 0.20H), 7.32-7.16 (m, 5H), 6.03 (br
s, 1H), 3.31 (major rotamer, q, J = 6.8 Hz, 1.62H), 3.20
-
1
1003, 971, 910, 885, 811, 751, 654, 531 cm ; HRMS (ESI)
－
(
minor rotamer, q, J = 6.8 Hz, 0.37H), 2.68-2.63 (m, 2H),
m/z [M+HCO
found 172.09779.
N-[2-(3,4-dimethoxyphenyl)ethyl]formamide
Purified by TLC; Yellow oil; Isolated yield 72%; H NMR
2
H-H]
8 3
calcd for C H14NO 172.09682,
1
3
1
3
.89-1.81 (m, 2H); C NMR (100 MHz, CDCl ) δ 164.90
[
23]
(
minor rotamer), 161.47 (major rotamer), 141.24 (major
(2x)
:
1
rotamer), 140.64 (minor rotamer), 128.66 (minor rotamer),
28.54 (major rotamer), 128.41 (major rotamer), 126.30
minor rotamer), 126.13 (major rotamer), 41.15 (minor
rotamer), 37.82 (major rotamer), 33.19 (major rotamer),
1
(
3
(400 MHz, CDCl ) δ 8.12 (major rotamer, s, 0.85H), 7.90
(minor rotamer, d, J = 12 Hz, 0.15H), 6.83-6.68 (m, 3H),
5.96 (br s, 1H), 3.87 (major rotamer, s, 4.10H), 3.86 (minor
rotamer, s, 2.46H), 3.54 (major rotamer, q, J = 6.7 Hz,
3
2.58 (minor rotamer), 32.51 (minor rotamer), 31.15
(
major rotamer); IR (neat) 3122, 1666, 1402, 1154, 1113,
1.73H), 3.45 (minor rotamer, q, J = 6.7 Hz, 0.39H), 2.85-
-
1
+
13
7
49, 701 cm ; HRMS (ESI) m/z [M+Na] calcd for
2.74 (m, 2H); C NMR (100 MHz, CDCl
3
) δ 164.60
C
10
H
13NNaO 186.08894, found 186.08968.
(minor rotamer), 161.33 (major rotamer), 149.07 (minor
rotamer), 148.99 (major rotamer), 147.87 (minor rotamer),
147.69 (major rotamer), 130.99 (major rotamer), 130.12
(minor rotamer), 120.90 (minor rotamer), 120.66 (major
rotamer), 111.91 (minor rotamer), 111.80 (major rotamer),
111.41 (minor rotamer), 111.30 (major rotamer),
55.91(major rotamer), 55.87(minor rotamer), 43.35 (minor
rotamer), 39.34 (major rotamer), 37.32 (minor rotamer),
35.09 (major rotamer); IR (neat) 3140, 3006, 2941, 2838,
1668, 1610, 1593, 1519, 1467, 1400, 1265, 1238, 1195,
[
20]
N-(1-phenylethyl)formamide (2s) : Purified by TLC;
1
Yellow oil; Isolated yield 87%; H NMR (400 MHz,
CDCl ) δ 8.11 (s, 1H), 7.34-7.25(m, 5H), 6.32 (br s, 1H),
3
5
.21-5.14 (m, 0.83H), 4.71-4.65 (m, 0.20H), 1.55 (minor
rotamer, d, J = 6.8 Hz, 0.57H), 1.49 (major rotamer, J =
1
3
6
1
1
3
.8 Hz, 2.52H); C NMR (100 MHz, CDCl ) δ 160.46,
42.64, 128.95 (minor rotamer), 128.76 (major rotamer),
27.79 (minor rotamer), 127.54 (major rotamer), 126.17
(
major rotamer), 125.81 (minor rotamer), 51.76 (minor
-
1
rotamer), 47.63 (major rotamer), 23.61 (minor rotamer),
1159, 1142, 1029, 937, 859, 811, 810, 766, 632 cm ;
+
2
1
1.81 (major rotamer); IR (neat) 3100, 1662, 1534, 1497,
HRMS (ESI) m/z [M+H] calcd for C11
found 210.11217.
H
16NO
3
210.11247,
-
1
402, 1238, 1118, 762, 698, 609 cm ; HRMS (ESI) m/z
+
[24]
[
M+H] calcd for C
9
H
12NO 150.09134, found 150.09122.
N-acetyl-1,2,3,4-tetrahydroisoquinoline
(2za)
1
:
[
21]
N-Formyl-1-indanamin (2t) : Purified by TLC; Yellow
Purified by TLC; Yellow oil; Isolated yield 94%; H NMR
o
1
solid; Isolated yield 80%; mp 109-110 C; H NMR (400
3
(400 MHz, CDCl ) δ 7.20-7.13 (m, 4H), 4.72 (major
MHz, CDCl
(
1
3
) δ 8.24 (major rotamer, s, 0.90H), 8.20
rotamer, s, 1.15H), 4.61 (minor rotamer, 0.85H), 3.81
(minor rotamer, t, J = 6.0 Hz, 0.85H), 3.67 (major rotamer,
t, J = 6.0 Hz, 1.12H), 2.91 (major rotamer, t, J = 5.8 Hz,
1.17H), 2.85 (minor rotamer, t, J = 6.0 Hz, 0.82H), 2.18
minor rotamer, s, 0.10H), 7.29-7.20 (m, 4H), 5.98 (br s,
H), 5.54 (major rotamer, q, J = 8.0 Hz, 0.80H), 4.98
(
minor rotamer, q, J = 8.5 Hz, 0.19H), 3.02-2.95 (m, 1H),
2
.91-2.83 (m, 1H), 2.64-2.56 (m, 1H), 1.92-1.78 (m, 1H);
(minor rotamer, s, 1.42H), 2.17 (major rotamer, s, 1.61H);
13
13
C NMR (100 MHz, CDCl
3
) δ 163.95 (minor rotamer),
3
C NMR (100 MHz, CDCl ) δ 169.65 (major rotamer),
1
60.99 (major rotamer), 143.46 (major rotamer), 142.59
169.56 (minor rotamer), 135.10 (minor rotamer), 134.04
(major rotamer), 133.50 (major rotamer), 132.55 (minor
rotamer), 128.97 (minor rotamer), 128.31 (major rotamer),
126.95 (minor rotamer), 126.69 (major rotamer), 126.65
(major rotamer), 126.57 (minor rotamer), 126.39 (major
rotamer), 126.06 (minor rotamer), 48.10 (minor rotamer),
44.12 (major rotamer), 44.04 (major rotamer), 39.53
(minor rotamer), 29.46 (major rotamer), 28.53 (minor
rotamer), 21.97 (minor rotamer), 21.70 (major rotamer); IR
(neat) 3159, 3029, 2933, 2857, 1661, 1634, 1456, 1403,
1374, 1299, 1284, 1254, 1232, 1170, 1075, 1034, 1001,
(
minor rotamer), 128.49 (minor rotamer), 128.18 (major
rotamer), 127.06 (minor rotamer), 126.90 (major rotamer),
25.08 (minor rotamer), 124.91 (major rotamer), 124.02
major rotamer), 123.78 (minor rotamer), 57.46 (minor
rotamer), 53.35 (major rotamer), 35.16 (minor rotamer),
1
(
3
4.00 (major rotamer), 30.27 (major rotamer), 29.93
(
minor rotamer); IR (neat) 3118, 1640, 1547, 1402, 1154,
－
-
1
1
3 2
115, 751, 529 cm ; HRMS (ESI) m/z [M+CH CO H-H]
calcd for C12
H
14NO
3
220.09682, found 220.0971.
[
22]
N-(2-hydroxy-2-phenylethyl)formamide (2u) : Purified
1
-1
by TLC; Yellow oil; Isolated yield 58%; H NMR (400
930, 766, 652, 636, 602 cm ; HRMS (ESI) m/z
－
MHz, CDCl
3
) δ 8.09 (major rotamer, s, 0.83H), 7.87
[M+HCO
220.09813.
N-propionyl-1,2,3,4-tetrahydroisoquinoline
Purified by TLC; Yellow oil; Isolated yield 85%; H NMR
2 3
H-H] calcd for C12H14NO 220.09682, found
(
minor rotamer, d, J = 12 Hz, 0.17H), 7.35-7.27 (m, 5H),
[
25]
6
0
3
1
.36 (br s, 1H), 4.80 (major rotamer, dd, J = 8.4, 3.6 Hz,
.84H), 4.71 (minor rotamer, dd, J = 7.6, 4.0 Hz, 0.17H),
.74-3.67 (major rotamer, m, 1.66H), 3.41-3.27 (m,
(2zb)
:
1
3
(400 MHz, CDCl ) δ 7.27-7.10 (m, 4H), 4.73 (major
13
.17H); C NMR (100 MHz, CDCl
3
) δ 165.53 (minor
rotamer, s, 1.12H), 4.61 (minor rotamer, 0.88H), 3.83
(minor rotamer, t, J = 6.0 Hz, 0.88H), 3.67 (major rotamer,
t, J = 5.8 Hz, 1.10H), 2.90 (major rotamer, t, J = 5.8 Hz,
1.15H), 2.84 (minor rotamer, t, J = 6.0 Hz, 0.90H), 2.46-
rotamer), 162.26 (major rotamer), 141.44 (major rotamer),
1
40.90 (minor rotamer), 128.76 (minor rotamer), 128.63
major rotamer), 128.27 (minor rotamer), 128.05 (major
rotamer), 125.92 (minor rotamer), 125.86 (major rotamer),
3.43 (minor rotamer), 72.96 (major rotamer), 49.32
minor rotamer), 45.79 (major rotamer); IR (neat) 3140,
670, 1523, 1495, 1402, 1239, 1198, 1096, 915, 755, 703
(
13
2.40 (m, 2H), 1.21-1.16 (m, 3H); C NMR (100 MHz,
7
(
3
CDCl ) δ 172.90 (major rotamer), 172.80 (minor rotamer),
135.23 (minor rotamer), 134.11 (major rotamer), 133.70
(major rotamer), 132.69 (minor rotamer), 128.97 (minor
rotamer), 128.25 (major rotamer), 126.90, 126.72, 126.59,
126.50, 126.33, 126.03, 47.26 (minor rotamer), 44.27
1
-
1
+
cm ; HRMS (ESI) m/z [M+H] calcd for C
9 2
H12NO
1
66.08626, found 166.08598.
6
This article is protected by copyright. All rights reserved.

European Journal of Organic Chemistry
10.1002/ejoc.201800253
(
major rotamer), 43.13 (major rotamer), 39.71 (minor
rotamer), 29.53 (major rotamer), 28.55 (minor rotamer),
7.04 (minor rotamer), 26.84 (major rotamer), 9.44 (major
4.55 (minor rotamer, s, 0.95H), 3.91 (minor rotamer, t, J =
5.6 Hz, 0.95H), 3.74 (major rotamer, t, J = 6.0 Hz, 1.07H),
2.92 (major rotamer, t, J = 5.8 Hz, 1.06H), 2.85 (minor
2
rotamer), 9.36 (minor rotamer); IR (neat) 3120, 2983, 2941, rotamer, t, J = 5.8 Hz, 0.97H), 2.19 (major rotamer, s,
13
2
1
607, 2361, 1942, 1694, 1646, 1454, 1401, 1310, 1223,
1.56H), 2.17 (minor rotamer, s, 1.45H); C NMR (100
MHz, CDCl ) δ 169.70 (minor rotamer), 169.52 (major
148, 1113, 1083, 1053, 980, 959, 807, 746, 706, 650, 583
3
－
-
1
cm ; HRMS (ESI) m/z [M+HCO
2
H-H]
calcd for
rotamer), 134.40 (minor rotamer), 132.47 (major rotamer),
132.15 (minor rotamer), 131.13 (major rotamer), 125.20
(major rotamer), 124.47 (minor rotamer), 123.65 (minor
rotamer), 123.48 (major rotamer), 46.43 (minor rotamer),
44.28 (major rotamer), 42.48 (major rotamer), 39.52
(minor rotamer), 25.63 (major rotamer), 24.74 (minor
rotamer), 22.04 (minor rotamer), 21.68 (major rotamer); IR
(neat) 3111, 3014, 2928, 2850, 1634, 1403, 1361, 1336,
1318, 1277, 1241, 1217, 1178, 1083, 1010, 893, 833, 708,
C
13
H
16NO
3
234.11247, found 234.11247.
3,4-dihydroisoquinolin-2(1H)-yl)(thiophen-2-
yl)methanone (2zc): Purified by TLC; Yellow oil; Isolated
(
1
3
yield 38%; H NMR (400 MHz, CDCl ) δ 7.46 (d, J = 4.8
Hz ,1H), 7.38 (d, J = 3.6 Hz ,1H), 7.20-7.06 (m, 5H), 4.87
(
s, 2H), 3.94 (t, J = 5.8 Hz, 2H), 2.96 (t, J = 5.8 Hz, 2H);
13
3
C NMR (100 MHz, CDCl ) δ 163.91, 137.58, 134.48,
1
1
2
8
[
(
33.00, 128.92, 128.88, 128.72, 126.84, 126.82, 126.59,
26.45, 44.92 (br s), 29.72, 29.19; IR (neat) 3152, 2361,
345, 1620, 1523, 1402, 1297, 1251, 1101, 1038, 980, 932,
-
1
+
656, 593 cm ; HRMS (ESI) m/z [M+Na] calcd for
11NSNaO 204.04536, found 204.04520.
9
C H
-
1
[30]
18, 740, 721 cm ; HRMS (ESI) m/z calcd for C14
H
12NSO
N-benzylacetamide (2zi) : Purified by TLC; A colorless
－
o 1
M-H] 242.06451, found 242.06397.
solid; Isolated yield 83%; mp 63.5-64.0 C; H NMR (400
MHz, CDCl ) δ 7.35-7.26 (m, 5H), 6.05(br s, 1H), 4.40 (d,
J = 5.6 Hz, 2H), 2.00 (s, 3H); C NMR (100 MHz, CDCl
δ 170.07, 138.25, 128.73, 127.86, 127.55, 43.74, 23.26; IR
H), 4.90 (major rotamer, s, 1.14H), 4.59 (minor rotamer, s, (neat) 3282, 1651, 1556, 1402, 1290, 1079, 1031, 734, 699,
3,4-Dihydroisoquinolin-2(1H)-yl)(phenyl)methanone
3
[
26]
13
(
2zd) : Purified by TLC; Yellow oil; Isolated yield 32%;
3
)
1
H NMR (400 MHz, CDCl
3
) δ 7.44 (s, 5H), 7.22-7.17(m,
4
0
-
1
+
.86H), 4.00 (minor rotamer, s, 0.69H), 3.64 (major
611, 574 cm ; HRMS (ESI) m/z [M+Na] calcd for
rotamer, s, 1.10H), 2.97 (minor rotamer, s, 0.95H), 2.88
9
C H11NNaO 172.07329, found 172.07275.
1
3
(
major rotamer, s, 1.24H); C NMR (100 MHz, CDCl
3
) δ
1-(4-phenylpiperazin-1-yl)propan-1-one (2zj): Purified
1
1
4
2
70.99 136.14, 133.00, 129.84, 128.56, 127.17-126.40(m),
9.84, 45.34, 44.88, 40.53, 29.72, 28.32; IR (neat) 3153,
363, 2345, 1633, 1402, 1299, 1258, 1107, 934, 753, 699
by TLC; Yellow oil; Isolated yield 78%; H NMR (400
3
MHz, CDCl ) δ 7.31-7.27 (m, 2H), 6.95-6.89 (m, 3H), 3.79
(t, J = 4.8 Hz, 2H), 3.62 (t, J = 4.6 Hz, 2H), 3.19-3.14 (m,
-
1
+
13
cm ; HRMS (ESI) m/z [M+H] calcd for C16
H
16NO
4H), 2.40 (q, J = 7.6 Hz, 2H), 1.18 (t, J = 7.6 Hz, 3H); C
2
38.12264, found 238.12215.
3
NMR (100 MHz, CDCl ) δ 172.36, 151.01, 129.27, 120.53,
[
27]
N-(4-phenylpiperazin-1-yl)acetamide (2ze) : Purified
116.66, 49.76, 49.44, 45.36, 41.49, 26.51, 9.53; IR (neat)
3137, 1653, 1601, 1498, 1402, 1157, 1029, 1075, 936, 760,
1
by TLC; Yellow oil; Isolated yield 89%; H NMR (400
MHz, CDCl
(
-
1
+
3
) δ 7.31-7.27 (m, 2H), 6.94-6.89 (m, 3H), 3.77
695, 527 cm ; HRMS (ESI) m/z [M+ Na] calcd for
t, J = 5.2 Hz, 2H), 3.62 (t, J = 5.2 Hz, 2H), 3.19-3.13 (m,
13 18 2
C H N NaO 241.13113, found 241.13052.
1
3
4
1
2
1
H), 2.14 (s, 3H); C NMR (100 MHz, CDCl
3
) δ 169.05,
N-methyl-N-phenethylpropionamide (2zk): Purified by
1
50.96, 129.28, 120.60, 116.70, 49.74, 49.40, 46.27, 41.38,
TLC; Yellow oil; Isolated yield 46%; H NMR (400 MHz,
3
1.42; IR (neat) 3152, 2820, 1644, 1597, 1504, 1433, 1280, CDCl ) δ 7.33-7.15 (m, 5H), 3.58 (t, J = 7.8 Hz, 1.05H),
-
1
230, 1158, 1115, 1034, 997, 906, 760, 695, 589, 527 cm ;
3.50 (t, J = 7.4 Hz, 0.95H), 2.96 (minor rotamer, s, 1.37H),
2.87 (major rotamer, s, 1.59H), 2.84 (t, J = 7.4 Hz, 2H),
2.31 (major rotamer, q, J = 7.2Hz, 1.07H), 2.13 (minor
rotamer, q, J = 7.6 Hz, 0.91H), 1.14 (major rotamer, t, J =
7.4 Hz, 1.60H), 1.04 (minor rotamer, t, J = 7.4 Hz, 1.39H);
+
HRMS (ESI) m/z [M+Na] calcd for C11
H
14
N
2
NaO
2
27.11548, found 227.11570.
N-methyl-N-phenethylacetamide (2zf): Purified by TLC;
1
Yellow oil; Isolated yield 83%; H NMR (400 MHz,
13
CDCl
3
) δ 7.33-7.15 (m, 5H), 3.58 (minor rotamer, t, J =
3
C NMR (100 MHz, CDCl ) δ 173.80 (minor rotamer),
7
2
1
1
.6 Hz, 0.98H), 3.50 (major rotamer, t, J = 7.2 Hz 1.02H),
173.60 (major rotamer), 139.32 (major rotamer), 138.28
(minor rotamer), 128.87 (minor rotamer), 128.77 (major
rotamer), 128.49, 126.75 (minor rotamer), 126.29 (major
rotamer), 51.60 (minor rotamer), 50.08 (major rotamer),
35.99 (minor rotamer), 34.92 (major rotamer), 33.86
(major rotamer), 33.58 (minor rotamer), 26.86 (major
rotamer), 25.93 (minor rotamer), 9.54 (minor rotamer),
9.25 (major rotamer); IR (neat) 3152, 1649, 1402, 1152,
.94 (major rotamer, s, 1.52H), 2.87 (minor rotamer, s,
.46H), 2.84 (t, J = 7.4 Hz, 2H), 2.06 (minor rotamer, s,
1
3
.45H), 1.84 (major rotamer, s, 1.50H); C NMR (100
MHz, CDCl
3
) δ 170.65, 170.51, 139.21 (minor rotamer),
38.20 (major rotamer), 128.83, 128.79, 128.77, 128.50,
26.79, 126.32, 52.59 (major rotamer), 49.75 (minor
1
1
rotamer), 36.89 (minor rotamer), 34.77 (major rotamer),
-
1
+
3
3.77 (major rotamer), 33.40 (minor rotamrer), 21.97
531 cm ; HRMS (ESI) m/z [M+H] calcd for C12
192.13829, found 192.13786.
H
18NO
(
minor rotamer), 20.96 (major rotamer); IR (neat) 3029,
2
7
935, 1651, 1402, 1305, 1202, 1129, 1079, 1033, 1005,
N-methyl-N-(naphthalen-1-ylmethyl)propionamide
-
1
+
1
53, 703, 595, 567 cm ; HRMS (ESI) m/z [M+ Na] calcd
15NNaO 200.10459, found 200.10386.
(2zl): Purified by TLC; Yellow oil; Isolated yield 55%; H
for C11
H
3
NMR (400 MHz, CDCl ) δ 8.09 (d, J = 8.0 Hz, 0.64H),
[
28]
N-methyl-N-(naphthalen-1-ylmethyl)acetamide (2zg)
:
7.93-7.79 (m, 2.36H), 7.59-7.32 (m, 3.69H), 7.20 (d, J =
7.2 Hz, 0.36H), 5.08 (major rotamer, s, 1.28H), 5.00
(minor rotamer, s, 0.72H), 3.08 (minor rotamer, s, 1.07H),
2.83 (major rotamer, s, 1.93H), 2.45-2.33 (m, 2H), 1.24-
1
Purified by TLC; Yellow oil; Isolated yield 86%; H NMR
(
(
0
1
3
400 MHz, CDCl ) δ 8.10 (d, J = 8.0 Hz, 0.66H), 7.92-7.79
m, 2.40H), 7.58-7.40 (m, 3.09H), 7.33 (d, J = 6.8 Hz,
13
.64H), 7.22 (d, J = 7.2 Hz, 0.36H), 5.06 (major rotamer, s,
3
1.13 (m, 3H); C NMR (100 MHz, CDCl ) δ 174.82
.27H), 4.99 (minor rotamer, s, 0.73H), 3.06 (minor
(minor rotamer), 173.70 (major rotamer), 133.88 (major
rotamer), 133.79 (minor rotamer), 132.95 (major rotamer),
131.78 (major rotamer), 131.70 (minor rotamer), 130.70
(minor rotamer), 129.08 (minor rotamer), 128.62 (major
rotamer), 128.41 (major rotamer), 128.01 (minor rotamer),
127.03 (minor rotamer), 126.50 (major rotamer), 126.06
(minor rotamer), 125.95 (major rotamer), 125.64 (minor
rotamer), 125.18 (major rotamer), 124.02, 122.40 (minor
rotamer), 122.00 (major rotamer), 51.12 (minor rotamer),
48.58 (major rotamer), 34.62 (minor rotamer), 34.04
(major rotamer), 27.02 (major rotamer), 26.14 (minor
rotamer), 9.60 (minor rotamer), 9.47 (major rotamer); IR
rotamer, s, 1.08H), 2.83 (major rotamer, s, 1.88H), 2.18
(
major rotamer, s, 1.94H), 2.12 (minor rotamer, s, 1.10H);
13
C NMR (100 MHz, CDCl
3
) δ 171.70 (minor rotamer),
1
70.56 (major rotamer), 133.89 (major rotamer), 133.81
(
minor rotamer), 132.72, 131.74, 131.44, 130.68, 129.09,
1
1
1
28.64, 128.50, 128.11, 127.06, 126.58, 126.55, 126.10,
25.99, 125.65, 125.18, 123.97, 122.46 (minor rotamer),
21.99 (major rotamer), 52.08 (minor rotamer), 48.40
(
major rotamer), 34.94 (major rotamer), 34.40 (minor
rotamer), 22.08 (major rotamer), 21.31 (minor rotamer); IR
-
1
(
neat) 3140, 1655, 1402, 1262, 1163, 792, 529 cm ;
+
-
HRMS (ESI) m/z [M+ Na] calcd for C14
H
15NNaO
(neat) 3144, 1651, 1510, 1403, 1256, 1120, 1066, 794 cm
1
+
2
5
36.10459, found 236.10408.
-acetyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridine
; HRMS (ESI) m/z [M+Na] calcd for C15H17NNaO
250.12024, found 250.11964.
[
29]
(
2zh) : Purified by TLC; A pale yellow oil; Isolated
1-(6,7-dihydrothieno[3,2-c]pyridin-5(4 H)-yl)propan-1-
1
yield 84%; H NMR (400 MHz, CDCl
3
)  7.16-7.12 (m,
one (2zm): Purified by TLC; Yellow oil; Isolated yield
1
1
H), 6.80-6.79 (m, 1H ), 4.66 (major rotamer, s, 1.05H),
61%; H NMR (400 MHz, CDCl
3
) δ 7.16-7.12 (m, 1H),
7
This article is protected by copyright. All rights reserved.

European Journal of Organic Chemistry
10.1002/ejoc.201800253
6
.81-6.78 (m, 1H), 4.68 (major rotamer, s, 1.04H), 4.54
minor rotamer, s, 0.96H), 3.93 (minor rotamer, t, J = 5.4
Hz, 0.97H), 3.74 (major rotamer, t, J = 5.4 Hz, 1.06H),
C. Nayler, G. N. Rolinson, Nature 1959, 183, 257−258; f)
Polyimides Fundamentals and Applications (Eds.: M. K.
Ghosh, K. L. Mittal), Marcel Dekker, New York, 1996.
[3] a) R. B. Sonawane, N. K. Rasal, S. V. Jagtap, Org. Lett.
(
2
.91-2.85 (m, 2H), 2.48-2.39 (m, 2H), 1.21-1.15 (m, 3H);
13
3
C NMR (100 MHz, CDCl ) δ 172.92, 172.77, 134.53,
32.69, 132.16, 131.24, 125.27, 124.48, 123.58, 123.39,
5.52 (minor rotamer), 43.34 (major rotamer), 42.63
1
4
2
017, 19, 2078−2081; b) T. M. El Dine, D. Evans, J.
Rouden, J. Blanchet, Chem. Eur. J. 2016, 22, 5894−5898;
c) T. B. Nguyen, J. Sorres, M. Q. Tran, L. Ermolenko, A.
Al-Mourabit, Org. Lett. 2012, 14, 3202−3205; d) Y.
Wang, F. Wang, C. Zhang, J. Zhang, M. Lia, J. Xu, Chem.
Commun. 2014, 50, 2438−2441; e) Y. Wang, J. Zhang, J.
Liu, C. Zhang, Z. Zhang, J. Xu, S. Xu, F. Wang, F. Wang,
ChemSusChem 2015, 8, 2066−2072; f) R. M. Lanigan, P.
Starkov, T. D. Sheppard, J. Org. Chem. 2013, 78,
(
major rotamer), 39.73 (minor rotamer), 27.09 (minor
rotamer), 26.85 (major rotamer), 25.74 (major rotamer),
4.78 (minor rotamer), 9.56 (major rotamer), 9.37 (minor
rotamer); IR (neat) 3122, 1648, 1429, 1402, 1264, 1224,
2
-
1
1
046, 1012, 889, 831, 706, 658, 595 cm ; HRMS (ESI)
+
m/z [M+Na] calcd for C10
H
13NSNaO 218.06101, found
2
18.06026.
N-benzylpropionamide (2zn) 31]: 1 Purified by TLC;
[
Yellow oil; Isolated yield 73%; H NMR (400 MHz,
CDCl
3
) δ 7.35-7.26 (m, 5H), 5.96 (br s, 1H), 4.42 (d, J =
4
512−4523; g) P. B. Thale, P. N. Borase, G. S.
5
3
1
1
.2 Hz, 2H), 2.23 (q, J = 7.6 Hz, 2H), 1.17 (t, J = 7.6 Hz,
13
H); C NMR (100 MHz, CDCl
3
) δ 173.74, 138.44,
Shankarling, RSC Adv. 2016, 6, 52724−52728; h) Q.
Zhang, C. Chen, J. Saudi Chem. Soc. 2016, 20, 114−119; i)
L. Becerra-Figueroa, A. Ojeda-Porras, D. Gamba-Sánchez,
J. Org. Chem. 2014, 79, 4544−4552; j) A. Chikkulapalli, S.
K. Aavula, M. N. P. Rifahath, C. Karthikeyan, K. C. H.
Vinodh, S. G. Manjunatha, S. Shanmugam, Tetrahedron
Lett. 2015, 56, 3799−3803; k) C. Liana Allen, B. N.
Atkinson, J. M. J. Williams, Angew. Chem. Int. Ed. 2012,
28.71, 127.82, 127.49, 43.57, 29.70, 9.91; IR (neat) 3289,
651, 1554, 1402, 1236, 1105, 1031, 732, 699, 501 cm ;
-
1
+
HRMS (ESI) m/z [M+Na] calcd for C10
H
13NNaO
1
86.08894, found 186.08897.
Gram reaction
A solution of 1,2,3,4-tetrahydroisoquinoline (1 g, 7.5
mmol), Co(OAc) •4H O (60 mg, 3 mol%) in DMF (8 mL)
2
2
5
1, 1383–1386; l) M. Zhang, S. Imm, S. Bähn, L. Neubert,
H. Neumann, M. Beller, Angew. Chem. Int. Ed. 2012, 51,
905−3909; m) S. N. Rao, D. C. Mohan, S. Adimurthy,
Org. Lett. 2013, 15, 1496–1499.
4] a) M. Hosseini-Sarvari, H. Sharghi, J. Org.
was stirred in a sealed tube under an atmosphere of argon
at 150°C for 24 h. After being cooled to room temperature,
the reaction mixture were filtered, washed with ethyl
acetate. Afterward, the solution was added 30 mL water
and extracted with ethyl acetate (4 × 30 mL), then the
combined organic layers were dried with anhydrous
3
[
Na
2
SO
4
. Afterward, the solution was evaporated under
Chem. 2006, 71, 6652−6654; b) Z. Chen, R. Fu, W. Chai,
H. Zheng, L. Sun, Q. Lu, R. Yuan, Tetrahedron 2014, 70,
vacuum. The residue was purified by silica gel column
chromatography with petroleum ether and ethyl acetate to
2
237−2245; c) B. Das, M. Krishnaiah, P.
obtain
the
pure
product
2-formyl-1,2,3,4-
tetrahydroisoquinoline (1.04 g, yield: 86%).
Balasubramanyam, B. Veeranjaneyulu, D. Nandankumar,
Tetrahedron Lett. 2008, 49, 2225−2227; d) G.
Brahmachari, S. Laskar, Tetrahedron Lett. 2010, 51,
Acknowledgements
2
319−2322; e) B. A. Aleiwi, K. Mitachi, M. Kurosu,
Tetrahedron Lett. 2013, 54, 2077−2081; f) M. Rahman, D.
Kundu, A. Hajra, A. Majee, Tetrahedron Lett. 2010, 51,
2896−2899; g) P. Ganapati Reddy, G. D. Kishorekumar, S.
Baskaran, Tetrahedron Lett. 2000, 41, 9149−9151.
We are grateful to the National Natural Science Foundation of
China (No. 21402168), Scientific Research Foundation of Hunan
Provincial Education Department (No. 15B232), National
Natural Science Foundation of Hunan Province (No.
2
018JJ2389), “1515” academic leader team program of Hunan
[
5] a) S. Chakraborty, U. Gellrich, Y. Diskin-Posner, G.
Agricultural University and Hunan 2011 Collaborative
Innovation Center of Chemical Engineering & Technology with
Environmental Benignity and Effective Resource Utilization for
their support of our research.
Leitus, L. Avram, D. Milstein, Angew. Chem. Int. Ed. 2017,
56, 4229−4233; b) B. Kang, S. H. Hong, Adv. Synth. Catal.
2
015, 357, 834−840; c) N. Ortega, C. Richter, F. Glorius,
Org. Lett. 2013, 15, 1776−1779; d) S. Tanaka, T. Minato,
E. Ito, M. Hara, Y. Kim, Y. Yamamoto, N. Asao, Chem.-A
Eur. J. 2013, 19, 11832−11836; e) B. Xu, R. J. Madix, C.
M. Friend, Chem.-A Eur. J. 2012, 18, 2313−2318.
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Full Article
Cobalt (II)-Catalyzed N-Acylation of Amines via
Transamidation Reaction
Eur. J. Org. Chem. Year, Volume, Page – Page
Juan Ma, Feng Zhang, Jingyu Zhang, Hang Gong*,
An efficient, practical Co(II)-catalyzed N-acylation of various amines using readily available and
inexpensive DMF and other amides as carbonyl sources is described.
1
0
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