Palladium-catalyzed C8-H alkoxycarbonylation of 1-naphthylamines with alkyl chloroformates

Article abstract of DOI:10.1039/d0ob00586j

A simple and efficient protocol for palladium-catalyzed C8-H alkoxycarbonylation of 1-naphthylamine derivatives with alkyl chloroformates has been developed, exhibiting broad functional group tolerance, high regioselectivity, and oxidant-free conditions. Furthermore, the reaction features its ease of further functionalization and transformation. For example, the concise synthesis of one BET bromodomain inhibitor was accomplished via benz[cd]indol-2(1H)-one after multistep transformations from the obtained alkoxycarbonylation product. In addition, the control experiments suggest that the reaction might involve a radical process and the C-H bond cleavage might not be involved in the rate-determining step.

Full text of DOI:10.1039/d0ob00586j

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Palladium-Catalyzed C8-H Alkoxycarbonylation of
-Naphthylamines with Alkyl Chloroformates
1
a
a
a
Yaqi Shi, Fan Yang * and Yangjie Wu *
Received 00th January 20xx,
Accepted 00th January 20xx
A simple and efficient protocol for palladium-catalyzed C8-H alkoxycarbonylation of 1-naphthylamine
derivatives with alkyl chloroformates has been developed, exhibiting broad functional group tolerance, high
regioselectivity, and oxidant-free conditions. Furthermore, the reaction features its ease of further
functionalization and transformation. For example, the concise synthesis of one BET bromodomain inhibitor
was accomplished via benz[cd]indol-2(1H)-one after multistep transformations from the obtained
DOI: 10.1039/x0xx00000x
alkoxycarbonylation product. In addition, the control experiments suggest that the reaction might involve a
radical process and the C-H bond cleavage might not be involved in the rate-determining step.
Introduction
Previous work
Aromatic esters, as a type of important synthetic building
blocks, are ubiquitous in many fields, such as pharmaceutical
industries, natural products, and materials science. Therefore,
the synthesis of organic compounds containing such structural
moiety has attracted synthetic chemists’ efforts. The traditional
synthetic methodologies for these compounds relied on either
the reaction of activated acid derivatives with alcohols or the
transition metal-catalyzed cross-coupling reaction of aryl
halides with carbon monoxide.2
RuCl2(PPh3)3 (10 mol %)
K2CO3 (2.5 equiv)
N
O
N
O
+
Cl
O
(a)
(b)
1
toluene, 120 °C, 12 h
O
Pd(OAc)2 (10 mol %)
Ag CO (2.0 equiv)
O
O
2
3
+
O
O
NH
Cl
O
O
NH
toluene, 100 °C, N , 8 h
2
N
N
This work
The C-H carbonylation/esterification reactions have been
proven to be an important tool towards synthesis of
amides/lactams, carboxylic acids, esters, ketones, and
anhydrides involving carbon monoxide as a carbonyl source.3
However, carbon monoxide as the carbonyl source have its
drawbacks of high toxicity, flammability, explosibility, and
difficult handling of gaseous carbon monoxide. Since Yu and
co-workers developed the first palladium-catalyzed oxidative
ethoxycarbonylation of aromatic C–H bonds with diethyl
azodicarboxylate (DEAD),4a many groups have successfully
O
O
Pd(OAc)2 (15 mol %)
NaOAc (2.0 equiv)
N
O
O
O
N
HN
HN
+
(c)
Cl
O
NaI (1.0 equiv)
toluene, 120 °C, Ar, 12 h
Scheme 1. Ligand-directed regioselective C-H alkoxycarbonylation
In 2009, the ruthenium-catalyzed direct alkoxycarbonylation
of the aromatic C–H bonds with alkyl chloroformates was
described by Kakiuchi and co-workers (Scheme 1a).11a
Subsequently,
Shi
disclosed
the
Pd(II)-catalyzed
3
stereoselective alkoxycarbonylation of C(sp )–H bonds with
alkyl chloroformates.11b And then, they realized the
alkoxycarbonylation of aromatic C–H bonds using 8-
aminoquinoline moiety (AQ) as a directing group (Scheme
b).11c Despite these advances, the above alkoxycarbonylation
protocols belong to the ortho-C-H functionalization, and the
catalytic C8–H of 1-Naphthylamines alkoxycarbonylation
remains rare.
achieved
carbonylative
transformations
with
4
azodicarboxylate. Other esterification reagents also appeared,
such as carbon dioxide, glyoxylate, α-keto esters, di-tert
5
6
7
-
butyl decarbonate (Boc
2
O),8 formates,9 and potassium
1
1
0
oxalate. Although the abovementioned carboxylation reagents
have been widely utilized in the synthesis of ester compounds,
investigating new avenues for direct C–H alkoxycarbonylation
would be highly desirable.
Since Daugulis and co-workers introduced the picolinamide
(
PA) moiety as a bidentate directing group in 2005,12 several
catalytic versions for regioselective C-H functionalization of 1-
naphthylamine have been achieved.13 The research interest in
our group mainly focuses on the remote C-H functionalization
of arene derivatives at an unusual site, especially at the C4 or
C5 site of 8-aminoquinoline derivatives14 and the C415 or
aCollege of Chemistry, Green Catalysis Center, Henan Key Laboratory of Chemical
Biology and Organic Chemistry, Key Laboratory of Applied Chemistry of Henan
Universities, Zhengzhou University, Zhengzhou 450052, P R China
E-mail: yangf@zzu.edu.cn, wyj@zzu.edu.cn
Electronic Supplementary Information (ESI) available: [details of any supplementary
information available should be included here]. See DOI: 10.1039/x0xx00000x
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ARTICLE
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C813d,13j,13k site of 1-naphthylamide derivatives. Just recently,
an efficient palladium-catalyzed C8-H acylation of 1-
naphthylamines was developed in our group.13j Inspired by
abovementioned pioneering examples, herein we envisioned
showcasing a simple and efficient protocol for direct C8–H
alkoxycarbonylation of 1-naphthylamides with alkyl
chloroformates (Scheme 1c).
Results and discussion
2
Initially, the Pd(OAc) -catalyzed reaction of N-(naphthalen-1-
yl) picolinamide 1a with isopropyl chloroformate 2a was
performed in the presence of NaOAc in toluene, and
gratifyingly, the desired product 3aa was obtained in 57% yield
(
Table 1, entry 1). However, other palladium species did not
provide comparable yields of the product 3aa (Table 1, entries
-6). Then, various bases were examined, and NaOAc was the
best base with high yield of 57% (Table 1, entry 1 vs. entries 7-
2 and the ESI). Subsequently, different additives were
examined, NaI exhibited the best activity for this reaction
Table 1, entries 13-16). However, a catalytic amount of NaI
did not afford the products with better results (Table 1, entries
7 and 18 vs. entry 14). Finally, some control experiments were
2
1
(
1
performed (Table 1, entries 19-23). Both the palladium catalyst
and the base played important roles for this successful catalytic
reaction (Table1, entries 19 and 20). When the catalyst loading
was increased to 15 mol %, the product was obtained in a higher
yield of 88% (Table 1, entry 21 vs. entry 14). However, when
o
the temperature reduced to 100 C, the yield of 3aa was
Table 1. Optimization of the reaction conditionsa
Scheme 2. Scope of 1-(Naphthalenyl)picolinamides
decreased to 48% (Table 1, entry 22 vs. entry 21). The reaction
could also be conducted under air, albeit generating the product
in a lower yield of 77% (entry 23 vs entry 21)
.
entry
catalyst
base
additive
Yield
b
With the optimized reaction conditions in hand, the substrate
scope of N-(naphthalen-1-yl)picolinamide derivatives with
isopropyl chloroformate 2a was explored, and the results are
summarized in Scheme 2. Generally, the reaction could tolerate
various electron-donating and -withdrawing substituents in the
pyridine ring or the naphthalene moiety, affording the
corresponding products in moderate to good yields (3ba-3qa).
Comparatively, substrates bearing electron-donating groups
could result in products in slightly higher yields of than those
of substrates bearing electron-withdrawing groups in the
pyridine ring (3ca and 3da vs. 3ea-3ga). Substrates bearing an
ortho-substituent in the pyridine ring would lead to lower yields
(
%)
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
Pd(OAc)
Pd(TFA)
2
2
NaOAc
NaOAc
NaOAc
NaOAc
NaOAc
NaOAc
-
-
-
-
-
57
45
43
32
<5
26
40
43
41
35
44
47
<5
81
73
16
68
72
<5
<5
88
PdCl
2
Pd(CH
3
2 2
CN) Cl
Pd
2
dba
3
PdI
2
Pd(OAc)
Pd(OAc)
Pd(OAc)
Pd(OAc)
Pd(OAc)
Pd(OAc)
Pd(OAc)
Pd(OAc)
Pd(OAc)
Pd(OAc)
Pd(OAc)
Pd(OAc)
-
2
2
2
2
2
2
2
2
2
2
2
2
Na
2
CO
3
-
-
-
-
-
-
K
2
CO
3
Na
Na
3
PO
4
0
1
2
3
4
5
6
7
8
9
0
1
2
HPO
4
EtONa
tBuONa
NaOAc
NaOAc
NaOAc
NaOAc
NaOAc
NaOAc
NaOAc
-
I
2
NaI
KI
AgSbF
NaI
NaI
NaI
NaI
NaI
6
c
(
3ba vs. 3ca), which may be attributed to the ortho-steric effect.
d
Notably, the AQ directing group possessing a benzene ring
moiety would accelerate reaction, affording the product 3ha in
a high yield of 92%. However, the similar result of 3ia was
obtained to that of 3ba probably due to the steric effect of the
C8-H bond in the isoquinoline moiety. The electron-poor
directing group did not have advantage to this reaction and
result in the product 3ja in a low yield of 23%. The substrates
bearing electron-donating or -withdrawing groups at the C4 or
C5 site in the naphthalene ring could afford the desired products
Pd(OAc)
Pd(OAc)
Pd(OAc)
Pd(OAc)
2
2
e
NaOAc
NaOAc
NaOAc
e,f
e,g
2
2
2
3
2
2
NaI
NaI
48
77
a
Reaction conditions: 1a (0.1 mmol), 2a (0.3 mmol), Pd catalyst (10
mol %), base (0.2 mmol) and an additive in toluene (1.0 mL) at 120
C under argon for 12 h. Isolated yield based on 1a
o
b
c
. With an
d
additive loading of 30 mol %. With an additive loading of 50 mol
e
f
o
g
%
. With a catalyst loading of 15 mol %. At 100 C. Under air.
2
| J. Name., 2012, 00, 1‐3
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a
Reagents and conditions: (a) CH
3
CH
2 3
I, NaH, DMF, rt; (b) HNO ,
o
o
AcOH, 0-50 C, 1 h; (c) Fe, NH
4
Cl, AcOH, 50 C, 30 min; (d) 5-
2 2
Bromo-2-methoxybenzenesulfonyl chloride, CH Cl , pyridine, rt.
Scheme 4. Synthetic Applications
In order to demonstrate the synthetic utility of this protocol,
a gram scale reaction and some potential applications of the
Scheme 3. Scope of Various Chloroformates
in moderate yields (3ka-3oa). Especially, the molecular esterification product were completed (Scheme 4). A gram
structure of 3na was unambiguously confirmed by single- scale reaction of 1a (7 mmol, 1.736 g) was investigated under
1
8
crystal X-ray diffraction study. However, when there was a the standard conditions, affording the product 3aa (1.075 g) in
a moderate yield of 46% (Scheme 4a). The experiment of
removal of the directing group was carried out, and
benz[cd]indol-2(1H)-one 4a was successfully obtained in 55%
yield via the hydrolysis process of 3aa (Scheme 4b).
substituent at the C7 or C2 site in the naphthalene ring, the
reactivity was switched off and few products 3ra and 3sa
can be obtained due to the strong steric hindrance.
Subsequently, the substrate scope of chloroformates and aryl Benz[cd]indol-2(1H)-one 4a as a significant skeleton is
chlorides were also explored under the standard reaction frequently found in pharmaceuticals, natural products, and
conditions (Scheme 3). Chloroformates containing a wide range biologically active compounds, and notably, the BET inhibitor
of aliphatic groups were employed in this reaction, affording is a new class of potent BET bromodomain inhibitor with anti-
the desired products in mostly moderate yields (3ab-3ec). tumor and anti-inflammatory activities.16 Herein its facile
Moreover, the 3-chloropropyl chloroformate 2e could also synthesis was successfully achieved from benz[cd]indol-2(1H)-
tolerated in this reaction, providing the product in moderate one 4a. First, alkyl substitution product 5a was obtained by
yields of 52% and 75%, respectively (3de and 3he). However, nucleophilic substitution of 4a with iodoalkane in 96% yield.
in the case of benzyl chloroformate 2f as an esterification Then, nitration reaction of 5a with nitric acid took place to
reagent, the desired product 3df was obtained in a lower yield afford the product 6a in 67% yield, followed by a nitro
of 21%. In addition, allyl chloroformate 2g was also checked in reduction in the presence of iron and AcOH to form 7a in 77%
this reaction, albeit generating the target products in lower yield. Finally, the sulfonamidation occurred to provide the BET
yields of 23% and 32%, respectively (3bg and 3hg). Finally, the bromodomain inhibitor 8a in a high yield of 88% (Scheme 4c).
reaction was also suitable to traditional aryl chlorides, although
In order to gain insight into the mechanism, several control
providing the target products in relatively lower yields, which
experiments were conducted (Scheme 5). Some designed
is attributed to the electron-poor property of the aryl chlorides
substrates (A–D) were first explored under the standard
reaction conditions, but no esterification products were
(
3ah-3aj).
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addition of radical scavenger of 2,2,6,6-tetramethylpiperidin-1-
oxyl (TEMPO) successfully suppressed the reaction (Scheme
5b). When the reaction were performed in the presence of
TEMPO or 2,6-di-tert-butyl-4-methylphenol (BHT), an adduct
of TEMPO and isopropyl chloroformate 2a as the product 9a
and an adduct of BHT and N-(naphthalen-1-yl) picolinamide 1a
as the product 10a could be detected by HR-MS, respectively
(
Scheme 5c). These results suggested that the reaction might
involve a radical process. Finally, the experiment of the
kinetic isotope effect (KIE) was carried out, and the result
(
KIE = 0.3) may imply that the C–H bond cleavage might
not be involved in the rate-determining step (Scheme 5d)
.
Based on the above experimental results and previous reports,13
a plausible mechanism is proposed in Scheme 6. First, the
coordination of the substrate 1a to the Pd(II) species with the
help of a base occurs to afford a bischelated metallacyclic Pd(II)
intermediate
iodine anion to generate an intermediate radical
radical under the standard heating conditions. Subsequently, the
reaction of the intermediate with the iodine radical undergoes
A
. The isopropyl chloroformate 2a reacts with
D
and an iodine
A
a single electron transfer (SET) process to generate iodine anion
and
an intermediate radical
process to generate a Pd(III) intermediate
oxidative addition of the intermediate radical
intermediate forms a Pd(IV) intermediate , the reductive
elimination of which takes place to afford a Pd(II) intermediate
. Finally, the ligand dissociation of the resulting Pd(II)
intermediate occurs to provide the corresponding naphthyl
B
, followed by an intramolecular SET
.17 Next, the
to the
C
+
+
D
HRMS (ESI ) for 9a: calcd for C13
H26NO
3
[M+H] : 244.1907, found:
2
44.1908.
C
E
F
F
ester 3aa and regenerate the catalytically active Pd(II) species
to fulfil the catalytic cycle.
+
+
HRMS (ESI ) for 10a: calcd for C31
H
35 2
N O
2
[M+H] : 467.2693,
found: 467.2692.
Scheme 6. Proposed Reaction Mechanism
Scheme 5. Control Experiments
Conclusions
observed, demonstrating that the N,N-bidentate directing group
may be essential in this transformation (Scheme 5a). The
4
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In conclusion, we have developed an efficient and convenient
General Procedures for the Deprotection of Directing Groups.
protocol for palladium-catalyzed regioselective C8-H bond A mixture of 3aa (66.8 mg, 0.2 mmol, 1.0 equiv) and NaOH (240 mg,
o
6
mmol, 30 equiv) was heated in ethanol (3.0 mL) for 12 h at 80 C.
alkoxycarbonylation of 1-naphthylamine derivatives with
chloroformates. The reaction proceeded smoothly under
oxidant-free conditions, which showed broad functional group
tolerance and high regioselectivity. Remarkably, the reaction
offered a convenient alternative to the concise synthesis of one
BET bromodomain inhibitor.
After the mixture was cooled to room temperature and diluted with
water (3.0 mL), the solution of diluted hydrochloric acid was added
until it was acidic. The saturated NaHCO
until the pH value was about 7. The mixture was then extracted with
CH Cl and dried over anhydrous Na SO . After the organic material
3
solution was then added
2
2
2
4
was concentrated in vacuum, the product was purified by column
chromatography on silica gel (100‒200 mesh) using hexane/EtOAc as
an eluent (3:1, V/V) to afford the pure product 4a.
Experimental section
General Information
General Procedures for the BET bromodomain inhibitor. To a
solution of 4a (169 mg, 1.0 mmol, 1.0 equiv) in DMF (2.5 mL), NaH
1H NMR and 13C NMR spectra were recorded on a Bruker DPX-400
spectrometer with CDCl as the solvent and TMS as an internal
3
o
(
36 mg, 1.5 mmol, 1.5 equiv) was added at 0 C. After stirred for 10
o
min at 0 C, iodoethane (96 µL, 1.2 mmol, 1.2 equiv) was added
dropwise into the solution and the reaction mixture was stirred at room
temperature. After the reaction was completed, the resulting mixture
standard. Melting points were measured using a WC-1 microscopic
apparatus and are uncorrected. High resolution mass spectra were
ensured on an Agilent Technologies 1290-6540 UHPLC/Accurate-
Mass Quadrupole Time-of-Flight LC/MS. All solvents were used
directly without further purification. Dichloromethane, ethyl acetate,
and hexane were used for column chromatography. The commercials
were obtained from commercial sources and used as-received without
further purification unless otherwise noted. Chemical shift
multiplicities are represented as follows: s = singlet, d = doublet, t =
triplet, m = multiplet, dd = double doublet, td = three doublets. Unless
otherwise mentioned, all materials were commercially obtained and
used without further purification.
was poured into H
material was dried over Na
product was purified by column chromatography on silica gel (100‒
00 mesh) using hexane/EtOAc as an eluent (5:1, V/V) to afford the
2
O and extracted with ethyl acetate. The organic
2
SO and concentrated in vacuum, and the
4
2
pure product 5a.
To a solution of 5a (189 mg, 0.96 mmol, 1.0 equiv) in AcOH (2.5
o
mL), HNO
3
(61 mg, 0.96 mmol, 1.0 equiv) was added at 0 C and then
o
the reaction mixture was stirred at 50 C for 1 h. After the reaction
was completed, the reaction mixture was cooled to room temperature.
The mixture was extracted with ethyl acetate, dried over anhydrous
Preparation of Naphthalene. A 100 mL two-necked round-
bottom flask was equipped with a magnetic stir bar and charged with
2 4
Na SO and concentrated in vacuo, and the product was purified by
column chromatography on silica gel (100‒200 mesh) using
hexane/EtOAc as an eluent (5:1, V/V) to afford the pure product 6a.
1
-naphthylamine (20 mmol, 2.86 g), picolinic acid (1.1 equiv, 2.70 g),
N,N-dimethyl-4-aminopyridine (DMAP, 0.1 equiv, 0.244 g) in 30 mL
o
anhydrous CH Cl
2 2
at 0 C. After EDCI (4.20 g, 1.1 equiv) in CH
Cl
2 2
A mixture of iron powder (179 mg, 3.2 mmol, 5.0 equiv) and NH
4
Cl
(
20 mL) was added dropwise to the solution under a nitrogen
(
68 mg, 1.28 mmol, 2.0 equiv) in a mixture of AcOH/water (2 mL/8
atmosphere, the reaction was then warmed to room temperature,
stirred for 12 h and quenched with water (30 mL). The reaction
mL) was heated at 50 °C for 5 min. Subsequently, 6a (155 mg, 0.64
mmol, 1.0 equiv) was dissolved in DMF (2 mL) and added to the
reaction mixture. After completion, the mixture was cooled to room
temperature, extracted with ethyl acetate. After the organic layer was
mixture was extracted with CH
organic solvent was dried over Na
2
Cl
2
(3 × 20 mL), and the combined
SO , filtered and concentrated
2
4
under reduced pressure. The resulting residue was purified by column
chromatography (hexane/ethyl acetate = 3:1) (V/V) to afford the pure
product 1a as a white solid (4.42 g, 89%).
2 4
washed with brine, dried over Na SO and filtered, the filtrate was
concentrated in vacuo. The product was purified by column
chromatography on silica gel (100‒200 mesh) using hexane/EtOAc as
an eluent (3:1, V/V) to afford the pure product 7a.
All amides were prepared from the corresponding 1-naphthylamine
derivatives and 2-picolinic acid according to the reported procedure.19
A mixture of 7a (105 mg, 0.5 mmol, 1.0 equiv) and 5-bromo-2-
methoxybenzenesulfonyl chloride (170 mg, 0.6 mmol, 1.2 equiv) in
General Experimental Procedure for alkoxycarbonylation
reaction. A Schlenk tube was equipped with a magnetic stir bar and
charged with N-(naphthalen-1-yl)picolinamide 1a (0.1 mmol, 24.8
CH
temperature for 2 h. The mixture was extracted with CH
organic layer was washed with brine, dried over anhydrous Na
2
Cl
2
(10 mL) was added in pyridine (0.5 mL) and stirred at room
Cl , and the
SO
2
2
2
4
mg), 2a (0.3 mmol, 41 µL), NaOAc (0.2 mmol, 16 mg), Pd(OAc)
2
and filtered. The filtrate was concentrated in vacuo, and the product
was purified by column chromatography on silica gel (100‒200 mesh)
using hexane/EtOAc as an eluent (2:1, V/V) to afford the pure product
(
0.015 mmol, 3.3 mg), NaI (0.1 mmol, 15 mg) in toluene (1.0 mL).
o
The resulting mixture was sealed under argon, heated at 120 C for 12
h, and cooled to room temperature. Upon completion, CH Cl (20 mL)
2
2
8
a.16
was added to the reaction system, and the resulting mixture was
filtered through a pad of Celite. After the organic material was
concentrated in vacuum, the product was purified by column
chromatography on silica gel (100‒200 mesh) using hexane/EtOAc as
an eluent (5:1, V/V) to afford the pure product 3aa.
A Gram scale Synthesis. A oven-dried, 500 mL round-bottom
flask with Condensing return pipe was equipped with a magnetic stir
bar and charged with N-(naphthalen-1-yl)picolinamide 1a (7.0 mmol,
1.736 g), 2a (21.0 mmol, 2.5 mL), NaOAc (14.0 mmol, 1.1 g),
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Pd(OAc)
Journal Name
2
(10.5 mmol, 231.0 mg), NaI (7.0 mmol, 1.0 g) in toluene 149.2, 148.7, 140.2, 135.1, 132.1, 131.4, 129.2, 128.6, 127.7, 126.7,
+
(
1
150 mL). The resulting mixture was sealed under argon, heated at 126.3, 125.6, 124.6, 124.4, 124.3, 69.5, 21.6; HRMS (ESI ): calcd for
20 C for 12 h, and cooled to room temperature. Upon completion,
Cl (150 mL) was added to the reaction system. After the organic
o
+
20
C H
18BrN
2
O
3
[M+H] : 413.0495, found: 413.0497.
CH
2
2
Isopropyl 8-(5-chloropicolinamido)-1-naphthoate, 3fa: yellow
material was concentrated in vacuum, the product was purified by
column chromatography on silica gel (100‒200 mesh) using
hexane/EtOAc as an eluent (5:1, V/V) to afford the pure product 3aa.
o
1
solid (18.8 mg, 51%); mp 102-104 C; H NMR (400 MHz, CDCl
3
) δ
0.27 (s, 1H), 8.66 (d, J = 2.09 Hz, 1H), 8.25 (d, J = 8.27 Hz, 1H),
.00 (dd, J = 8.19 Hz, J = 0.88 Hz, 1H), 7.91-7.84 (m, 3H), 7.69 (dd,
= 7.11 Hz, J = 1.26 Hz, 1H), 7.62 (t, J = 7.83 Hz, 1H), 7.50-7.46
1
8
1
2
Characterization Data of the Products. Isopropyl 8-
J
1
2
(
1
picolinamido)-1-naphthoate, 3aa: yellow solid (29.4 mg, 88%); mp (m, 1H), 5.18-5.11 (m, 1H), 1.24 (d, J = 6.28 Hz, 6H); 13C NMR (100
o
1
10-112 C; H NMR (400 MHz, CDCl
3
3
) δ 10.37 (s, 1H), 8.72-8.70 MHz, CDCl ) δ 170.8, 162.6, 148.4, 147.1, 137.2, 135.4, 135.1, 132.1,
(
7
7
m, 1H), 8.30-8.28 (m, 1H), 7.98 (dd, J
.92-7.88 (m, 2H), 7.84 (d, J = 7.20 Hz, 1H), 7.67-7.62 (m, 2H), 7.49- 21.6; HRMS (ESI ): calcd for C20
.45 (m, 2H), 5.15-5.09 (m, 1H), 1.20 (d, J = 6.28 Hz, 6H); 13C NMR found: 369.0998.
1
= 8.24 Hz, J
2
= 1.12 Hz, 1H), 131.5, 129.2, 128.6, 127.7, 126.7, 126.3, 125.6, 124.6, 123.9, 69.5,
+
+
2 3
H18ClN O [M+H] : 369.1000,
(100 MHz, CDCl
3
) δ 170.8, 163.5, 150.2, 148.1, 137.5, 135.1, 131.9,
Isopropyl 8-(4-chloropicolinamido)-1-naphthoate, 3ga: white
1
6
31.7, 129.4, 128.3, 127.5, 126.7, 126.5, 126.4, 125.7, 124.6, 122.8,
9.5, 21.6; HRMS (ESI ): calcd for C20H N O [M+H] : 335.1390,
19 2 3
o
1
+
+
solid (28.3 mg, 77%); mp 146-148 C; H NMR (400 MHz, CDCl
3
) δ
0.35 (s, 1H), 8.61 (d, J = 5.24 Hz, 1H), 8.29 (d, J = 1.92 Hz, 1H),
.00-7.98 (m, 1H), 7.91 (d, J = 7.44 Hz, 1H), 7.85 (d, J = 8.00 Hz,
1
8
found: 335.1391.
Isopropyl
8-(3-methylpicolinamido)-1-naphthoate,
3ba: 1H), 7.70-7.68 (m, 1H), 7.62 (t, J = 7.82 Hz, 1H), 7.52-7.47 (m, 2H),
colorless solid (14.3 mg, 41%); mp 113-115 C; H NMR (400 MHz, 5.17-5.11 (m, 1H), 1.23 (d, J = 6.28 Hz, 6H); 13C NMR (100 MHz,
o
1
CDCl
dd, J
H), 7.49-7.45 (m, 1H), 7.40-7.37 (m, 1H), 5.04-4.98 (m, 1H), 2.76 HRMS (ESI ): calcd for C20
s, 3H), 1.16 (d, J = 6.28 Hz, 6H); 13C NMR (100 MHz, CDCl
) δ 369.1002.
70.8, 165.1, 147.3, 145.5, 141.0, 136.2, 135.1, 132.1, 131.7, 130.0,
28.0, 127.3, 126.8, 126.3, 126.0, 124.5, 69.3, 21.5, 20.7; HRMS
3
) δ 10.39 (s, 1H), 8.55 (dd, J
1 2 3
= 4.56 Hz, J = 1.04 Hz, 1H), 7.97 CDCl ) δ 170.7, 162.4, 151.7, 149.0, 146.0, 135.1, 132.2, 131.4,
(
3
(
1
1
1
= 8.24 Hz, J = 1.12 Hz, 1H), 7.88-7.82 (m, 2H), 7.65-7.59 (m, 129.1, 128.7, 127.7, 126.7, 126.4, 125.6, 124.6, 123.5, 69.5, 21.6;
2
+
+
2 3
H18ClN O [M+H] : 369.1000, found:
3
Isopropyl 8-(quinoline-2-carboxamido)-1-naphthoate, 3ha:
o
1
+
+
yellow solid (35.3 mg, 92%); mp 93-95 C; H NMR (400 MHz,
21 2
(ESI ): calcd for C21H N O3, [M+H] : 349.1547, found: 349.1549.
3
CDCl ) δ 10.67 (s, 1H), 8.40-8.32 (m, 3H), 7.99-7.97 (m, 2H), 7.90
Isopropyl 8-(6-methylpicolinamido)-1-naphthoate, 3ca: yellow (dd, J
1
= 8.06 Hz, J = 1.02 Hz, 1H), 7.84-7.79 (m, 2H), 7.68-7.60 (m,
2
o
1
solid (31.7 mg, 91%); mp 109-110 C; H NMR (400 MHz, CDCl
3
) δ 3H), 7.49-7.45 (m, 1H), 5.09-5.03 (m, 1H), 1.01 (d, J = 6.28 Hz, 6H);
0.43 (s, 1H), 8.09 (d, J = 7.64 Hz, 1H), 7.97 (d, J = 8.08 Hz, 1H), 13C NMR (100 MHz, CDCl
) δ 170.9, 163.7, 149.9, 146.5, 137.7,
1
7
(
(
1
1
3
.90 (d, J = 7.40 Hz, 1H), 7.83-7.75 (m, 2H), 7.65-7.58 (m, 2H), 7.46 135.2, 131.9, 130.3, 129.9, 129.5, 129.4, 128.3, 128.2, 127.8, 127.5,
t, J = 7.62 Hz, 1H), 7.34 (d, J = 7.68 Hz, 1H), 5.09-5.02 (m, 1H), 2.70 126.6, 126.4, 125.8, 124.6, 119.1, 69.3, 21.5; HRMS (ESI ): calcd for
+
s, 3H), 1.13 (d, J = 6.28 Hz, 6H); 13C NMR (100 MHz, CDCl
) δ
70.7, 163.8, 157.3, 149.4, 137.6, 135.1, 132.0, 129.5, 128.1, 127.4,
26.6, 126.4, 126.2, 125.8, 124.5, 119.8, 69.1, 24.1, 21.6; HRMS
+
3
C
24
H
21
2
N O
3
[M+H] : 385.1547, found: 385.1548.
Isopropyl 8-(isoquinoline-1-carboxamido)-1-naphthoate, 3ia:
+
+
o
1
(
ESI ): calcd for C21
H
21
N
2
O
3
[M+H] : 349.1547, found: 349.1548.
colorless solid (16.9 mg, 44%); mp 84-85 C; H NMR (400 MHz,
CDCl ) δ 10.57 (s, 1H), 9.62-9.59 (m, 1H), 8.63 (d, J = 5.52 Hz, 1H),
Isopropyl 8-(5-methoxypicolinamido)-1-naphthoate, 3da: 8.01-7.97 (m, 2H), 7.89-7.84 (m, 3H), 7.75-7.63 (m, 4H), 7.50-7.46
3
brown solid (28.8 mg, 79%); mp 76-79 C; H NMR (400 MHz, (m, 1H), 5.00-4.94 (m, 1H), 1.08 (d, J = 6.28 Hz, 6H); 13C NMR (100
CDCl ) δ 10.18 (s, 1H), 8.36 (d, J = 2.80 Hz, 1H), 8.24 (d, J = 8.64 MHz, CDCl
) δ 170.9, 165.1, 148.2, 140.2, 137.5, 135.2, 132.0, 131.9,
Hz, 1H), 7.90 (dd, J
o
1
3
3
1
= 8.24 Hz, J
2
= 1.12 Hz, 1H), 7.89 (d, J = 7.44, 130.6, 129.5, 128.9, 128.2, 127.8, 127.5, 127.3, 126.9, 126.8, 126.4,
+
Hz, 1H), 7.83-7.81 (m, 1H), 7.66-7.58 (m, 2H), 7.48-7.45 (m, 1H), 125.9, 124.8, 124.6, 69.4, 21.5; HRMS (ESI ): calcd for C24
H
21
N
2
O
3
+
7
3
1
1
.33 (dd, J
H), 1.22 (d, J = 6.28 Hz, 6H); 13C NMR (100 MHz, CDCl
63.4, 158.1, 142.8, 136.4, 135.1, 131.9, 131.8, 129.5, 128.1, 127.3,
1
= 8.68 Hz, J
2
= 2.84 Hz, 1H), 5.15-5.09 (m, 1H), 3.93 (s, [M+H] : 385.1547, found: 385.1548.
3
) δ 170.8,
Isopropyl 8-(pyrimidine-4-carboxamido)-1-naphthoate, 3ja:
1
26.7, 126.4, 125.8, 124.5, 124.1, 120.3, 69.5, 55.8, 21.6; HRMS yellow oil (7.7 mg, 23%); H NMR (400 MHz, CDCl
3
) δ 10.47 (s,
+
+
(
ESI ): calcd for C21
H
21
N
2
O
4
[M+H] : 365.1496, found: 365.1498.
1H), 9.41 (d, J = 1.28 Hz, 1H), 9.04 (d, J = 5.00 Hz, 1H), 8.22 (dd, J
5.02 Hz, J = 1.34 Hz, 1H), 8.02 (dd, J = 8.22 Hz, J
Isopropyl 8-(5-bromopicolinamido)-1-naphthoate, 3ea: yellow 1H), 7.93 (d, J = 7.48 Hz, 1H), 7.87 (d, J = 8.08 Hz, 1H), 7.76 (dd, J
1
=
2
1
2
= 1.06 Hz,
1
o
1
solid (21.4 mg, 52%); mp 85-87 C; H NMR (400 MHz, CDCl
0.28 (s, 1H), 8.77 (dd, J = 2.22 Hz, J = 0.58 Hz, 1H), 8.18 (dd, J
8.32 Hz, J = 0.56 Hz, 1H), 8.04 (dd, J = 8.32 Hz, J = 2.28 Hz, MHz, CDCl
H), 7.99 (dd, J = 8.24 Hz, J = 1.12 Hz, 1H), 7.90 (d, J = 7.48 Hz, 129.2, 128.8, 128.1, 126.8, 126.3, 125.4, 124.7, 119.1, 69.7, 21.6;
H), 7.84 (d, J = 8.16 Hz, 1H), 7.69 (dd, J
H), 7.61 (t, J = 7.84 Hz, 1H), 7.50-7.46 (m, 1H), 5.18-5.11 (m, 1H), 336.1342.
3
) δ = 7.12 Hz, J
2
= 1.20 Hz, 1H), 7.63 (t, J = 7.84 Hz, 1H), 7.52-7.48 (m,
1H), 5.24-5.18 (m, 1H), 1.26 (d, J = 6.24 Hz, 6H); 13C NMR (100
1
=
1
1
1
1
1
2
1
2
1
2
3
) δ 170.1, 161.9, 159.4, 157.8, 156.8, 135.2, 132.5, 130.9,
1
2
+
+
1
2
= 7.10 Hz, J = 1.26 Hz, HRMS (ESI ): calcd for C19
18 3 3
H N O [M+H] : 336.1343, found:
.24 (d, J = 6.28 Hz, 6H); 13C NMR (100 MHz, CDCl
3
) δ 170.7, 162.8,
6
| J. Name., 2012, 00, 1‐3
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Page 7 of 11
Or gP al en ai cs e& d Bo i on mo to al edc j uu lsat r mC ha re gmi ni ss try
View Article Online
DOI: 10.1039/D0OB00586J
Journal Name
ARTICLE
Isopropyl
5-acetoxy-8-(picolinamido)-1-naphthoate,
3ka: δ 170.4, 163.7, 149.5, 146.4, 137.8, 133.2, 131.9, 130.9, 130.6, 130.4,
) δ 10.28 (s, 130.2, 129.9, 129.5, 128.8, 128.3, 127.8, 127.3, 126.8, 126.1, 121.6,
1
brown oil (18.4 mg, 47%); H NMR (400 MHz, CDCl
3
+
[M+H]+:
1
H), 8.70 (d, J = 4.52 Hz, 1H), 8.29 (d, J = 7.76 Hz, 1H), 8.06-8.04 119.0, 69.5, 21.0; HRMS (ESI ): calcd for C24
H
20
N
O
2 3
(m, 1H), 7.92-7.87 (m, 2H), 7.66 (d, J = 6.28 Hz, 1H), 7.54-7.49 (m, 463.0652, found: 463.0653.
2
H), 7.41 (d, J = 8.20 Hz, 1H), 5.11-5.05 (m, 1H), 2.47 (s, 3H), 1.19
d, J = 6.28 Hz, 6H); 13C NMR (100 MHz, CDCl
Isopropyl
naphthoate, 3qa: yellow solid (29.1 mg, 63%); mp 137-139 C; H
NMR (400 MHz, CDCl ) δ 10.54 (s, 1H), 8.37-8.31 (m, 4H), 7.99 (d,
J = 7.44 Hz, 1H), 7.93-7.91 (m, 1H), 7.85-7.80 (m, 2H), 7.75-7.71 (m,
H), 7.69-7.65 (m, 1H), 7.46 (d, J = 7.68 Hz, 1H), 5.00-4.94 (m, 1H),
Isopropyl 4-methoxy-8-(picolinamido)-1-naphthoate, 3la: 0.99 (d, J = 6.28 Hz, 6H); 13C NMR (100 MHz, CDCl
) δ 170.1, 163.8,
brown solid (25.1 mg, 69%); mp 156-158 C; H NMR (400 MHz, 149.6, 146.4, 137.7, 133.4, 132.3, 130.4, 129.9, 129.7, 129.5, 129.1,
CDCl ) δ 10.55 (s, 1H), 8.69 (d, J = 4.56 Hz, 1H), 8.31-8.26 (m, 2H), 128.3, 127.9, 127.8, 127.7, 127.6, 127.3, 126.8, 126.6, 119.1, 69.6,
.96 (d, J = 7.32 Hz, 1H), 7.87 (t, = 7.70 Hz, 1H), 7.72 (d, J = 8.08 21.4; HRMS (ESI ): calcd for C24
4-bromo-8-(quinoline-2-carboxamido)-1-
(
1
1
3
) δ 170.4, 169.3,
o
1
63.6, 149.9, 148.1, 145.2, 137.5, 129.9, 129.7, 128.5, 128.2, 126.8,
26.6, 126.4, 125.2, 124.6, 122.9, 118.9, 69.7, 21.5, 21.1; HRMS
3
+
+
21 2 5
(ESI ): calcd for C22H N O [M+H] : 393.1445, found: 393.1444.
1
3
o
1
3
+
+
7
20 2 3
H N O [M+H] : 463.0652, found:
Hz, 1H), 7.61 (t, = 7.96 Hz, 1H), 7.48-7.45 (m, 1H), 6.76 (d, J = 8.04 463.0653.
Hz, 1H), 5.19-5.12 (m, 1H), 4.00 (s, 3H), 1.21 (d, J = 6.28 Hz, 6H);
13C NMR (100 MHz, CDCl
Propyl 8-(picolinamido)-1-naphthoate, 3ab: yellow solid (30.1
3
) δ 170.4, 163.5, 158.3, 150.3, 148.1,
o
1
mg, 90%); mp 108-110 C; H NMR (400 MHz, CDCl
1H), 8.72-8.70 (m, 1H), 8.31-8.28 (m, 1H), 7.99 (dd, J
= 1.16 Hz, 1H), 7.93-7.89 (m, 2H), 7.86-7.84 (m, 1H), 7.69 (dd, J
.08 Hz, J
Isopropyl 4-amino-8-(picolinamido)-1-naphthoate, 3ma: brown 2H), 4.11 (t, J = 6.82 Hz, 2H), 1.66-1.57 (m, 2H), 0.83 (t, J = 7.44 Hz,
3
) δ 10.31 (s,
1
1
37.4, 131.7, 130.4, 127.3, 127.2, 127.0, 126.4, 125.7, 122.8, 121.3,
+
1
= 8.28 Hz, J
2
21.1, 102.3, 69.1, 55.9, 21.6; HRMS (ESI ): calcd for C21
H
21
N
2
O
4
+
1
=
[M+H] : 365.1496, found: 365.1499.
7
2
= 1.28 Hz, 1H), 7.62 (t, J = 7.82 Hz, 1H), 7.53-7.46 (m,
o
1
) δ 3H); 13C NMR (100 MHz, CDCl
solid (13.3 mg, 38%); mp 130-133 C; H NMR (400 MHz, CDCl
3
3
) δ 171.3, 163.5, 150.0, 149.1, 137.5,
1
=
7
6
1
6
0.78 (s, 1H), 8.72-8.71 (m, 1H), 8.43 (d, J = 7.48 Hz, 1H), 8.36 (d, J 135.1, 131.9, 131.6, 129.1, 128.3, 127.6, 126.8, 126.6, 126.4, 125.9,
+
7.80 Hz, 1H), 8.00-7.89 (m, 3H), 7.74 (d, J = 8.56 Hz, 1H), 7.60- 124.6, 122.8, 67.6, 21.7, 10.3; HRMS (ESI ): calcd for C20
.52 (m, 3H), 7.01 (s, 1H), 5.12-5.06 (m, 1H), 1.35 (d, J = 6.24 Hz, [M+H] : 335.1390, found: 335.1393.
H
19
N
2
O
3
+
H); 13C NMR (100 MHz, CDCl
33.5, 133.0, 127.0, 126.6, 126.2, 126.1, 122.5, 118.7, 117.3, 116.9,
) δ 162.3, 154.0, 149.9, 148.2, 137.8,
3
Hexadecyl 8-(picolinamido)-1-naphthoate, 3ac: yellow solid
(17.5 mg, 34%); mp 66-68 C; H NMR (400 MHz, CDCl ) δ 10.32
3
o
1
+
+
9.1, 22.2; HRMS (ESI ): calcd for C20
H
20
3
N O
3
[M+H] : 350.1499,
(
J
s, 1H), 8.71-8.70 (m, 1H), 8.30-8.28 (m, 1H), 7.99 (dd, J
= 1.08 Hz, 1H), 7.93-7.88 (m, 2H), 7.85-7.83 (m, 1H), 7.68 (dd, J
Isopropyl 5-bromo-8-(picolinamido)-1-naphthoate, 3na: yellow = 7.08 Hz, J = 1.24 Hz, 1H), 7.62 (t, J = 7.84 Hz, 1H), 7.52-7.46 (m,
) δ 2H), 4.14 (t, J = 6.88 Hz, 2H), 1.60-1.55 (m, 2H), 1.25-1.20 (m, 26H),
0.87 (t, J = 6.68 Hz, 3H); 13C NMR (100 MHz, CDCl
) δ 171.3, 163.5,
.00 Hz, 1H), 8.28 (d, = 7.84 Hz, 1H), 7.93-7.88 (m, 2H), 7.75 (d, J = 150.1, 148.1, 137.5, 135.1, 131.9, 131.7, 129.1, 128.3, 127.5, 126.7,
1
= 8.28 Hz,
found: 350.1051.
2
1
2
o
1
solid (31.3 mg, 76%); mp 114-116 C; H NMR (400 MHz, CDCl
3
1
1
8
0.26 (s, 1H), 8.70 (d, J = 4.48 Hz, 1H), 8.45 (dd, J
1
= 8.52 Hz, J
2
=
3
.12 Hz, 1H), 7.68 (dd, J
1
= 7.04 Hz, J
2
= 1.12 Hz, 1H), 7.61-7.57 (m, 126.5, 126.4, 125.9, 124.6, 122.9, 66.3, 31.9, 29.7, 29.7, 29.7, 29.6,
H), 7.52-7.49 (m, 1H), 5.11-5.04 (m, 1H), 1.18 (d, J = 6.28 Hz, 6H); 29.6, 29.5, 29.4, 29.2, 28.4, 25.9, 22.7, 14.1; HRMS (ESI ): calcd for
+
1
1
3C NMR (100 MHz, CDCl
C
[M+H] : 517.3425, found: 517.3427.
+
3
) δ 170.2, 163.5, 149.8, 148.1, 137.6,
33
H
45 2
N O
3
1
1
33.1, 131.7, 130.9, 130.6, 130.1, 128.8, 127.2, 127.0, 126.7, 126.1,
+
Cyclopentyl 8-(picolinamido)-1-naphthoate, 3ad: yellow solid
22.9, 121.6, 69.8, 21.5; HRMS (ESI ): calcd for C20
H
18BrN
2
O
3
o
1
+
(18.7 mg, 52%); mp 95-97 C; H NMR (400 MHz, CDCl
s, 1H), 8.72 (d, J = 4.28 Hz, 1H), 8.29 (d, J = 7.80 Hz, 1H), 7.97 (dd,
= 8.22 Hz, J = 1.04 Hz, 1H), 7.92-7.88 (m, 2H), 7.83 (d, J = 8.08
) δ Hz, 1H), 7.64-7.59 (m, 2H), 7.51-7.45 (m, 2H), 5.25-5.22 (m, 1H),
0.27 (s, 1H), 8.71-8.69 (m, 1H), 8.34-8.28 (m, 2H), 7.93-7.88 (m, 1.69-1.65 (m, 6H), 1.54-1.50 (m, 2H); 13C NMR (100 MHz, CDCl
3
) δ 10.36
[M+H] : 413.0495, found: 413.0496.
(
J
Isopropyl 4-bromo-8-(picolinamido)-1-naphthoate, 3oa: yellow
1
2
o
1
solid (28.4 mg, 69%); mp 114-116 C; H NMR (400 MHz, CDCl
3
1
2
7
6
1
1
3
)
H), 7.80 (d, J = 7.68 Hz, 1H), 7.75-7.71 (m, 1H), 7.52-7.48 (m, 1H), δ 171.0, 163.5, 150.1, 148.1, 137.5, 135.1, 131.9, 131.7, 129.4, 128.3,
.45 (d, J = 7.68 Hz, 1H), 5.07-5.01 (m, 1H), 1.17 (d, J = 6.28 Hz, 127.5, 126.7, 126.5, 126.4, 125.8, 124.6, 122.8, 78.8, 32.6, 20.8;
H); 13C NMR (100 MHz, CDCl
+
+
3 21 2 3
) δ 170.0, 163.6, 149.8, 148.1, 137.6, HRMS (ESI ): calcd for C22H N O [M+H] : 361.1547, found:
33.4, 132.2, 129.6, 129.1, 127.9, 127.8, 127.7, 127.2, 126.8, 126.7, 361.1548.
+
26.6, 122.9, 69.8, 21.5; HRMS (ESI ): calcd for C20
H
18BrN
2
O
3
+
Hexadecyl 8-(5-bromopicolinamido)-1-naphthoate, 3ec: yellow
[M+H] : 413.0495, found: 413.0493.
o
1
solid (25.5 mg, 43%); mp 65-68 C; H NMR (400 MHz, CDCl
3
) δ
Isopropyl
naphthoate, 3pa: yellow solid (28.6 mg, 62%); mp 128-130 C; H
NMR (400 MHz, CDCl ) δ 10.54 (s, 1H), 8.48 (dd, J = 8.52 Hz, J
.24 Hz, 1H), 8.38 (s, 2H), 8.33 (d, J = 8.44 Hz, 1H), 7.96-7.93 (m, 7.62 (t, J = 7.84 Hz, 1H), 7.50-7.47 (m, 1H), 4.17 (t, J = 6.26 Hz, 2H),
H), 7.86-7.80 (m, 2H), 7.71-7.67 (m, 2H), 7.63-7.59 (m, 1H), 5.03- 1.64-1.55 (m, 2H), 1.25-1.22 (m, 26H), 0.88 (t, J = 6.80 Hz, 3H); 13
.97 (m, 1H), 1.00 (d, J = 6.28 Hz, 6H); 13C NMR (100 MHz, CDCl
NMR (100 MHz, CDCl ) δ 171.3, 162.7, 149.3, 148.6, 140.2, 135.1,
5-bromo-8-(quinoline-2-carboxamido)-1- 10.23 (s, 1H), 8.76 (d, J = 1.76 Hz, 1H), 8.20-8.17 (m, 1H), 8.04 (dd,
o
1
J
1
= 8.32 Hz, J
2
= 2.24 Hz, 1H), 8.00 (dd, J
1
= 8.24 Hz, J
2
= 1.00 Hz,
3
1
2
=
1H), 7.90-7.84 (m, 2H), 7.71 (dd, J
1
= 7.08 Hz, J
2
= 1.20 Hz, 1H),
1
2
4
C
3
)
3
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Organic & Biomolecular Chemistry
Page 8 of 11
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DOI: 10.1039/D0OB00586J
ARTICLE
Journal Name
+
+
1
1
2
5
32.1, 131.4, 128.9, 128.6, 127.7, 126.8, 126.4, 125.7, 124.6, 124.4, HRMS (ESI ): calcd for C24
H
19
N
O
2 3
[M+H] : 383.1390, found:
24.3, 66.3, 31.9, 29.7, 29.7, 29.7, 29.7, 29.6, 29.5, 29.4, 29.3, 28.5, 383.1392.
+
2 3
H44BrN O
[M+H]+:
5.9, 22.7, 14.2; HRMS (ESI ): calcd for C33
N-(8-benzoylnaphthalen-1-yl)picolinamide, 3ah: White solid (12.7
mg, 36%); mp 144-146 C; H NMR (400 MHz, CDCl
95.2530, found: 595.2531.
o
1
3
) δ 9.72 (s,
3
-Chloropropyl 8-(5-methoxypicolinamido)-1-naphthoate, 3de: 1H), 8.54-8.52 (m, 1H), 8.04-8.02 (m, 1H), 7.92 (d, J = 7.92 Hz, 1H),
o
1
brown solid (20.7 mg, 52%); mp 93-95 C; H NMR (400 MHz, 7.80-7.78 (m, 1H), 7.74-7.68 (m, 2H), 7.64-7.60 (m, 1H), 7.56-7.52
CDCl
) δ 10.07 (s, 1H), 8.37 (d, J = 2.68 Hz, 1H), 8.24 (d, J = 8.64 (m, 1H), 7.50-7.48 (m, 2H), 7.42-7.32 (m, 3H), 7.14-7.10 (m, 2H); 13
Hz, 1H), 7.99 (dd, J = 8.24 Hz, J = 1.00 Hz, 1H), 7.88-7.82 (m, 2H), NMR (100 MHz, CDCl ) δ 199.4, 163.1, 149.2, 147.9, 137.0, 136.9,
.67-7.59 (m, 2H), 7.49-7.46 (m, 1H), 7.33 (dd, J
3
C
1
2
3
7
2
1
= 8.68 Hz, J
2
=
136.0, 135.1, 133.2, 131.7, 130.5, 130.0, 128.0, 127.9, 127.8, 126.9,
+
.84 Hz, 1H), 4.30 (t, J = 6.24 Hz, 2H), 3.93 (s, 3H), 3.51 (t, J = 6.34 126.6, 126.5, 126.2, 124.9, 122.1; HRMS (ESI ): calcd for
Hz, 2H), 2.08-2.02 (m, 2H); 13C NMR (100 MHz, CDCl
) δ 171.1,
63.4, 158.3, 142.5, 136.5, 135.0, 132.0, 131.8, 128.7, 128.2, 127.5,
26.9, 126.5, 126.0, 124.6, 124.1, 120.5, 62.8, 55.9, 41.2, 31.3;
[M+H] : 353.1285, Found: 353.1287.
+
3
23
C H
16 2
N O
2
1
1
N-(8-(4-methylbenzoyl)naphthalen-1-yl)picolinamide,
3ai:
White solid (13.9 mg, 38%); mp 166-168 C; H NMR (400 MHz,
CDCl ) δ 9.72 (s, 1H), 8.55-8.53 (m, 1H), 8.03-8.00 (m, 1H), 7.91 (d,
J = 8.20 Hz, 1H), 7.81-7.79 (m, 1H), 7.75-7.68 (m, 2H), 7.63-7.59 (m,
8-(quinoline-2-carboxamido)-1-naphthoate, 1H), 7.55-7.52 (m, 1H), 7.42-7.38 (m, 4H), 6.91 (d, J = 7.96 Hz, 2H),
o
1
+
+
2 4
HRMS (ESI ): calcd for C21H20ClN O [M+H] : 399.1106, found:
3
99.1107.
3
3
-Chloropropyl
he: yellow solid (31.4 mg, 75%); mp 104-106 C; H NMR (400 2.27 (s, 3H); 13C NMR (100 MHz, CDCl
) δ 10.54 (s, 1H), 8.41-8.36 (m, 2H), 8.32 (d, J = 8.44 147.9, 144.1, 136.8, 136.2, 135.1, 134.6, 131.8, 130.4, 130.2, 128.6,
Hz, 1H), 8.02 (dd, J = 8.24 Hz, J = 1.04 Hz, 1H), 7.97-7.92 (m, 2H), 127.9, 127.7, 126.8, 126.5, 126.4, 126.2, 124.9, 122.1, 21.6; HRMS
.87-7.82 (m, 2H), 7.70-7.62 (m, 3H), 7.52-7.48 (m, 1H), 4.19 (t, J = (ESI ): calcd for C24
.22 Hz, 2H), 3.32 (t, J = 6.38 Hz, 2H), 1.90-1.83 (m, 2H); 13C NMR
) δ 171.1, 163.6, 149.6, 146.4, 137.8, 135.1, 132.1,
o
1
3
3
) δ 199.2, 163.2, 149.3,
MHz, CDCl
3
1
2
+
+
7
6
(
1
1
C
18 2 2
H N O [M+H] : 367.1441, Found: 367.1442.
N-(8-(4-chlorobenzoyl)naphthalen-1-yl)picolinamide,
White solid (11.8 mg, 36%); mp 174-177 C; H NMR (400 MHz,
3aj:
100 MHz, CDCl
3
o
1
31.8, 130.5, 129.8, 129.5, 128.7, 128.3, 128.3, 127.9, 127.6, 126.7,
+
CDCl ) δ 9.66 (s, 1H), 8.54 (d, J = 4.72 Hz, 1H), 8.03 (d, J = 8.12 Hz,
26.6, 125.9, 124.6, 119.1, 62.6, 40.9, 31.2; HRMS (ESI ): calcd for
3
+
1H), 7.92 (d, J = 8.04 Hz, 1H), 7.82-7. 81 (m, 1H), 7.77-7.73 (m, 1H),
24
H
20ClN
2
O
3
[M+H] : 419.1157, found: 419.1159.
7.71-7.69 (m, 1H), 7.64-7.61 (m, 1H), 7.56-7.53 (m, 1H), 7.44-7.37
Benzyl 8-(5-methoxypicolinamido)-1-naphthoate, 3df: brown (m, 4H), 7.07 (d, J = 8.56 Hz, 2H); 13C NMR (100 MHz, CDCl
) δ
3
1
3
oil (8.7 mg, 21%); H NMR (400 MHz, CDCl ) δ 10.17 (s, 1H), 8.31 198.2, 163.2, 149.1, 147.9, 139.7, 137.1, 135.4, 135.3, 135.1, 131.6,
(
d, J = 2.76 Hz, 1H), 8.23 (d, J = 8.64 Hz, 1H), 7.98 (dd, J
1
= 8.26 Hz, 131.3, 130.7, 128.2, 128.2, 128.0, 127.2, 126.7, 126.4, 126.4, 124.9,
+
+
J
2
= 1.10 Hz, 1H), 7.89 (d, J = 7.44 Hz, 1H), 7.83 (d, J = 8.16 Hz, 122.2; HRMS (ESI ): calcd for C23
H), 7.67-7.59 (m, 2H), 7.47-7.43 (m, 1H), 7.32-7.28 (m, 6H), 5.22 Found: 387.0894.
s, 2H), 3.91 (s, 3H); 13C NMR (100 MHz, CDCl
) δ 171.0, 163.4,
2 2
H15ClN O [M+H] : 387.0895,
1
(
3
Benzo[cd]indol-2(1H)-one, 4a: yellow solid (18.6 mg, 55%); mp
1
1
5
4
58.2, 142.6, 136.4, 135.5, 135.0, 132.0, 131.8, 128.7, 128.5, 128.3
28.3, 128.0, 127.4, 126.8, 126.5, 126.0, 124.6, 124.2, 120.4, 67.6,
o
1
1
73-176 C; H NMR (400 MHz, CDCl
7.00 Hz, 1H), 8.05 (d, J = 8.08 Hz, 1H), 7.76-7.72 (m, 1H), 7.56 (d, J
8.44 Hz, 1H), 7.48-7.44 (m, 1H), 7.03 (d, J = 7.00 Hz, 1H); 13C
3
) δ 9.10 (s, 1H), 8.11 (d, J =
+
+
5.8; HRMS (ESI ): calcd for C25
21 2
H N O
4
[M+H] : 413.1496, found:
=
13.1499.
NMR (100 MHz, CDCl
3
) δ 170.4, 137.2, 131.2, 129.4, 128.7, 126.8,
+
Allyl 8-(3-methylpicolinamido)-1-naphthoate, 3bg: brown solid 126.3, 124.5, 120.4, 106.7; HRMS (ESI ): calcd for C11
H
8
NO
o
1
+
(
(
7
(
J
1
1
8.0 mg, 23%); mp 119-121 C; H NMR (400 MHz, CDCl
s, 1H), 8.55-8.53 (m, 1H), 7.99 (dd, J = 8.24 Hz, J = 1.12 Hz, 1H),
.87-7.83 (m, 2H), 7.68-7.60 (m, 3H), 7.50-7.46 (m, 1H), 7.42-7.38
m, 1H), 5.89-5.79 (m, 1H), 5.23-5.12 (m, 2H), 4.57 (dt, J = 5.77 Hz,
= 1.26 Hz, 2H), 2.77 (s, 3H); 13C NMR (100 MHz, CDCl
) δ 170.8,
3
) δ 10.35 [M+H] : 170.0600, found: 170.0599.
1
2
1
-Ethylbenzo[cd]indol-2(1H)-one, 5a: yellow solid (189 mg,
o
1
9
6%); mp 65-68 C; H NMR (400 MHz, CDCl
3
) δ 8.00 (d, J = 6.96
1
Hz, 1H), 7.91 (d, J = 8.12 Hz, 1H), 7.64-7.60 (m, 1H), 7.45-7.37 (m,
2
3
2
7
H), 6.83 (d, J = 6.88 Hz, 1H), 3.92 (q, J = 7.24 Hz, 2H), 1.34 (t, J =
.24 Hz, 3H); 13C NMR (100 MHz, CDCl
) δ 167.7, 139.0, 130.6,
65.0, 147.0, 145.4, 141.1, 136.4, 135.1, 131.9, 131.8, 131.6, 128.9,
28.2, 127.4, 126.9, 126.4, 126.2, 126.1, 124.6, 118.6, 66.4, 20.8;
HRMS (ESI ): calcd for C21
3
+
+
129.0, 128.5, 128.4, 126.7, 125.1, 124.0, 120.1, 104.8, 34.9, 14.1;
19 2 3
H N O [M+H] : 347.1390, found:
+
+
HRMS (ESI ): calcd for C13
98.0915.
H12NO [M+H] : 198.0913, found:
3
47.1392.
1
Allyl 8-(quinoline-2-carboxamido)-1-naphthoate, 3hg: brown
o
1
1-Ethyl-6-nitrobenzo[cd]indol-2(1H)-one, 6a: yellow solid (155
solid (12.2 mg, 32%); mp 109-111 C; H NMR (400 MHz, CDCl
0.54 (s, 1H), 8.41-8.35 (m, 2H), 8.31 (d, J = 8.48 Hz, 1H), 8.02-7.92
m, 3H), 7.87-7.81 (m, 2H), 7.73-7.62 (m, 3H), 7.52-7.48 (m, 1H),
.78-5.67 (m, 1H), 5.05-4.95 (m, 2H), 4.55 (dt, J = 5.76 Hz, J = 1.36
Hz, 2H); 13C NMR (100 MHz, CDCl
) δ 170.8, 163.6, 149.7, 146.4,
37.7, 135.1, 132.0, 131.8, 131.5, 130.4, 129.9, 129.5, 128.8, 128.4,
3
) δ
o
1
mg, 67%); mp 158-161 C; H NMR (400 MHz, CDCl
8.52 Hz, 1H), 8.56 (d, J = 8.00 Hz, 1H), 8.06 (d, J = 6.96 Hz, 1H),
.86 (t, J = 7.76 Hz, 1H), 6.92 (d, J = 8.00 Hz, 1H), 3.99 (q, J = 7.20
Hz, 2H), 1.40 (t, J = 7.20 Hz, 3H); 13C NMR (100 MHz, CDCl
) δ
67.6, 145.6, 138.9, 131.9, 129.9,129.9, 126.0, 125.6, 125.3, 122.5,
3
) δ 8.89 (d, J
1
(
5
=
7
1
2
3
3
1
1
1
28.2, 127.8, 127.5, 126.6, 126.5, 125.9, 124.7, 119.2, 118.4, 66.4;
8
| J. Name., 2012, 00, 1‐3
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Or gP al en ai cs e& d Bo i on mo to al edc j uu lsat r mC ha re gmi ni ss try
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DOI: 10.1039/D0OB00586J
Journal Name
ARTICLE
+
[M+H]+:
1
2
02.9, 35.2, 13.9; HRMS (ESI ): calcd for C13
43.0764, found: 243.0762.
11
H N
O
2 3
J. B. Ni, J. Li, Z. L. Fan and A. Zhang, Org. Lett., 2016, 18
,
5
960-5963; (d) T. T. Nguyen, L. Grigorjeva and O. Daugulis,
Chem. Commun., 2017, 53, 5136-5138; (e) R. Sang, Y. Zheng,
H. L Zhang, X. H. Wu, Q. T. Wang, L. Hai and Y. Wu, Org.
1
-Ethyl-6-nitrobenzo[cd]indol-2(1H)-one, 7a: red solid (105 mg,
7%); mp 181-183 C; H NMR (400 MHz, CDCl ) δ 8.07 (d, J = 7.00
3
Hz, 1H), 8.00 (d, J = 8.16 Hz, 1H), 7.69-7.65 (m, 1H), 6.73 (d, J =
.44 Hz, 1H), 6.64 (d, J = 7.44 Hz, 1H), 3.94 (q, J = 7.24 Hz, 2H),
.41 (s, 2H), 1.35 (t, J = 7.24 Hz, 3H); 13C NMR (100 MHz, CDCl
Chem. Front., 2018,
D. Wu, Z. H. Guan and W. B. Liu, Org. Chem. Front., 2019,
, 1905-1928.
(a) H. Mizuno, J. Takaya and N. Iwasawa, J. Am. Chem. Soc.,
2011, 133, 1251-1253; (b) K. Sasano, J. Takaya and N.
5, 648-652; (f) M. Usman, X. W. Zhang,
o
1
7
6
7
3
5
3
)
Iwasawa, J. Am. Chem. Soc., 2013, 135, 10954-10957.
S. Z. Wang, Z. Y. Yang, J. D. Liu, K. Xie, A. W. Wang, X.
Chen and Z. Tan, Chem. Commun., 2012, 48, 9924-9926.
W. Zhou, P. H. Li, Y. C. Zhang and L. Wang, Adv. Synth.
Catal., 2013, 355, 2343-2352.
δ 167.3, 138.4, 131.1, 127.6, 127.4, 125.6, 125.3, 124.3, 121.5, 109.7,
6
7
8
9
+
13 2
H N
O [M+H]+:
1
2
06.5, 34.9, 14.1; HRMS (ESI ): calcd for C13
13.1022, found: 213.1023.
5-bromo-N-(1-ethyl-2-oxo-1,2-dihydrobenzo[cd]indol-6-yl)-2-
X. H. Hong, H. Wang, B. X. Liu and B. Xu, Chem. Commun.,
2014, 50, 14129-14132.
methoxybenzenesulfonamide, 8a: yellow solid (202 mg, 88%); mp
o
1
J. Wu, J. B. Lan, S. Y. Guo and J. S. You, Org. Lett., 2014, 16
862-5865.
0 Z. Y. Li and G. W. Wang, Org. Lett., 2015, 17, 4866-4869.
,
2
8
09-211 C; H NMR (400 MHz, CDCl
.00 (d, J = 6.96 Hz, 1H), 7.80-7.79 (m, 2H), 7.69-7.65 (m, 1H), 7.53
= 8.80 Hz, J = 2.48 Hz, 1H), 7.17 (d, J = 7.56 Hz, 1H), 6.90
d, J = 8.88 Hz, 1H), 6.71 (d, J = 7.60 Hz, 1H), 4.06 (s, 3H), 3.88 (q,
3
) δ 8.21 (d, J = 8.28 Hz, 1H),
5
1
1
(dd, J
1
2
1 (a) T. Kochi, S. Urano, H. Seki, E. Mizushima, M. Sato and F.
Kakiuchi, J. Am. Chem. Soc., 2009, 131, 2792-2793; (b) G.
Liao, X. S. Yin, K. Chen, Q. Zhang, S. Q. Zhang and B. F. Shi,
(
J = 7.20 Hz, 2H), 1.30 (t, J = 7.20 Hz, 3H); 13C NMR (100 MHz,
CDCl ) δ 167.6, 155.4, 138.1, 137.6, 133.2, 129.0, 128.2, 127.0,
26.8, 126.4, 126.1, 125.5, 124.8, 124.4, 113.9, 112.8, 104.8, 56.7,
Nat. Commun., 2016, 7, 12901-12909; (c) G. Liao, H. M. Chen
3
and B. F. Shi, Chem. Commun., 2018, 54, 10859-10862.
2 V. G. Zaitsev, D. Shabashov and O. Daugulis, J. Am. Chem.
Soc., 2005, 127, 13154-13155.
3 For selected examples on the picolinamide moiety directed C8-
H functionalization of naphthalene derivatives, see: (a) R.
Odani, K. Hirano, T. Satoh and M. Miura, J. Org. Chem., 2013,
1
3
4
1
1
+
2 4
H18BrN O
S [M+H]+:
5.0, 14.0; HRMS (ESI ): calcd for C20
61.0165, found: 461.0167.
7
8
, 11045-11052; (b) M. Iwasaki, W. Kaneshika, Y. Tsuchiya,
Conflicts of interest
K. Nakajima and Y. Nishihara, J. Org. Chem., 2014, 79
,
There are no conflicts to declare.
11330−11338; (c) L. Grigorjeva and O. Daugulis, Angew.
Chem. Int. Ed., 2014, 53, 10209-10212; (d) Z. X. Li, S. Y. Sun,
H. J. Qiao, F. Yang, Y. Zhu, J. X. Kang, Y. S. Wu and Y. J.
Wu, Org. Lett., 2016, 18, 4594-4597; (e) K. Takamatsu, K.
Hirano and M. Miura, Angew. Chem. Int. Ed., 2017, 56, 5353-
Acknowledgements
We are grateful to the National Natural Science Foundation of
5
357; (f) J. Y. Lan, H. S. Xie, X. X. Lu, Y. F. Deng, H. F. Jiang
and W. Zeng, Org. Lett., 2017, 19, 4279-4282; (g) Y. S. Xiong,
Y. Yu, J. Weng and G. Lu, Org. Chem. Front., 2018, , 982-
89; (h) S. Roy, S. Pradhan and T. Punniyamurthy, Chem.
Commun., 2018, 54, 3899-3902; (i) S. Rej and N. Chatani, ACS
Catal., 2018, , 6699-6706; (j) X. M. Yu, F. Yang, Y. S. Wu
China (nos. 21102134, 21172200) for financial support.
5
9
Notes and references
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and Y. J. Wu, Org. Lett., 2019, 21, 1726-1729; (k) X. L. Wang,
C. C. Feng, F. Yang and Y. J. Wu, Org. Biomol. Chem., 2019,
17, 4865-4868.
4 (a) H. J. Qiao, S. Y. Sun, F. Yang, Y. Zhu, W. Zhu, Y. X. Dong,
Y. S. Wu, X. T. Kong, L. Jiang and Y. J. Wu, Org. Lett., 2015,
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R. C. Larock, Comprehensive Organic Transformations: A
Guide to Functional Group Preparations, John Wiley & Sons:
New York, 1999.
1
2
3
J. Otera, Esterification: Methods, Reactions, and Applications,
Wiley-VCH: Weinheim, 2003.
For selected examples on the C–H carbonylation using carbon
monoxide as the carbonyl source, see: (a) K. F. Hogg, A.
Trowbridge, A. Alvarez-Perez and M. J. Gaunt, Chem. Sci.,
1
7
, 6086-6089; (b) M. M. Sun, S. Y. Sun, H. J. Qiao, F. Yang,
Y. Zhu, J. X. Kang, Y. S. Wu and Y. J. Wu, Org. Chem. Front.,
016, , 1646-1650; (c) H. J. Qiao, S. Y. Sun, F. Yang, Y. Zhu,
J. X. Kang, Y. S. Wu and Y. J. Wu, Adv. Synth. Catal., 2017,
59, 1976-1981; (d) H. J. Qiao, S. Y. Sun, Y. Zhang, H. M.
Zhu, X. M. Yu, Z. X. Li, F. Yang, Y. S. Wu and Y. J. Wu, Org.
Chem. Front., 2017, , 1981-1986.
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3
2
017,
Chen and W. J. Xiao, ACS Catal., 2019,
Giri and J. Q. Yu, J. Am. Chem. Soc., 2008, 130, 14082-14083;
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8
, 8198-8203; (b) B. Lu, Y. Cheng, L. Y. Chen, J. R.
3
9
, 8159-8164; (c) R.
4
(
1
1
5 (a) P. R. Bai, S. Y. Sun, Z. X. Li, H. J. Qiao, X. X. Su, F. Yang,
Y. S. Wu and Y. J. Wu, J. Org. Chem., 2017, 82, 12119-12127;
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32, 686-693; (e) B. Liu, F. Hu and B. F. Shi, ACS Catal.,
2
015, , 1863-1881. (f) R. R. Du, K. Zhao, J. H. Liu, F. Han,
5
(
b) H. M. Zhu, S. Y. Sun, H. J. Qiao, F. Yang, J. X. Kang, Y.
C. G. Xia and L. Yang, Org. Lett., 2019, 21, 6418-6422; (g) A.
Tlili, J. Schranck, J. Pospech, H. Neumann and M. Beller,
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X. F. Wu, Org. Lett., 2019, 21, 7624-7629; (i) Z. H. Guan, M.
Chen and Z. H. Ren, J. Am. Chem. Soc., 2012, 134, 17490-
S. Wu and Y. J. Wu, Org. Lett., 2018, 20, 620-623.
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P. Xiang, Z. Wang, Z. C. Tu, Y. L. Zhou, K. Ding and Y. Xu,
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C. C. Ge, Y. Chen, X. D. Liu, Y. X. Wang, Y. C. Yang, W.
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7493; (j) W. Z. Zhang, N. Zhang, Y. Q. Sun, Y. W. Ding and
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7
4
For selected examples on the C–H carbonylation using
azodicarboxylate as the carbonyl source, see: (a) W. Y. Yu, W.
N. Sit, K. M. Lai, Z. Y. Zhou and A. S. C. Chan, J. Am. Chem.
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7 (a) A. J. Hickman and M. S. Sanford, Nature, 2012, 484, 177-
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85; (b) D. C. Powers and T. Ritter, Acc. Chem. Res., 2012, 45,
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Huang and J. S. You, Org. Chem. Front., 2014, 1, 347-350; (c)
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DOI: 10.1039/D0OB00586J
ARTICLE
Journal Name
1
8
CCDC 1956109 (3na).† Crystal data for compound 3na
:
α
=
=
C
=
20
H
90°,
V
17BrN
b
= 1804.3(2) Å ,
2
O
3
,
M
= 413.26, monoclinic,
= 14.3268(8) Å, = 100.731(7)°,
= 293(2) K, space group =
a = 16.6385(13) Å,
β
c
= 7.7041(5) Å,
γ
Z
3
9
4
0°,
T
P2
1
/
c,
, reflections collected = 6920, independent reflections = 3221,
[
=
R
(int) = 0.0468], final
R
indices [ = 0.0486, w
I
> 2σ(
I
)]
R
1
R
2
0.1062, indices (all data)
R
R
1
= 0.0755, wR = 0.1265.
2
1
9 R. Shang, L. Ilies, E. Nakamura, J. Am. Chem. Soc., 2015, 137
660-7663.
,
7
1
0 | J. Name., 2012, 00, 1‐3
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Page 11 of 11
Organic & Biomolecular Chemistry
View Article Online
DOI: 10.1039/D0OB00586J
Palladium-Catalyzed C8-H Alkoxycarbonylation of
1
-Naphthylamines with Alkyl Chloroformates
R1
R1
N
N
R3
O
Pd(OAc)2 (15 mol %)
NaOAc (2.0 equiv)
O
O
H
HN
O
H
R2
HN
O
H
R2
R3
+
Cl
O
NaI (1.0 equiv)
toluene, 120 °C, 12 h
1
) regioselectively at the C8 site
26 examples
up to 92%
2
) oxidant-free conditions
A simple and efficient protocol for palladium-catalyzed C8-H alkoxycarbonylation of 1-naphthylamine derivatives with
alkyl chloroformates has been developed.