A Magnetically Recyclable Palladium-Catalyzed Formylation of Aryl Iodides with Formic Acid as CO Source: A Practical Access to Aromatic Aldehydes

Article abstract of DOI:10.1055/s-0040-1706621

A magnetically recyclable palladium-catalyzed formylation of aryl iodides under CO gas-free conditions has been developed by using a bidentate phosphine ligand-modified magnetic nanoparticles-anchored- palladium(II) complex [2P-Fe ₃O ₄@SiO ₂-Pd(OAc) ₂] as catalyst, yielding a wide variety of aromatic aldehydes in moderate to excellent yields. Here, formic acid was employed as both the CO source and the hydrogen donor with iodine and PPh ₃as the activators. This immobilized palladium catalyst can be obtained via a simple preparative procedure and can be facilely recovered simply by using an external magnetic field, and reused at least 9 times without any apparent loss of catalytic activity.

Full text of DOI:10.1055/s-0040-1706621

SYNTHESIS
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Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart
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021, 53, A–I
paper
A
en
Synthesis
S. You et al.
Paper
A Magnetically Recyclable Palladium-Catalyzed Formylation of
Aryl Iodides with Formic Acid as CO Source: A Practical Access to
Aromatic Aldehydes
Shengyong Youa,b
Rongli Zhanga
Mingzhong Cai*a
2
P-Fe
3
O
(
4
@SiO
3 mol%)
2 2
-Pd(OAc)
O
0
0
0
0
-
0
0
0
2
-
1
0
5
6
-
2
8
4
6
Ar
I
+
HCOOH
I
2
, PPh
3
, Et
3
N, toluene, 80 °C
Ar
H
a
37 examples
up to 93% yield
Key Laboratory of Functional Small Organic Molecule, Ministry of
Education and College of Chemistry & Chemical Engineering,
Jiangxi Normal University, Nanchang 330022, P. R. of China
mzcai@jxnu.edu.cn
Institute of Applied Chemistry, Jiangxi Academy of Sciences,
Nanchang 330029, P. R. of China
Broad substrate scope
Moderate to excellent yields
CO gas-free
Mild reaction conditions
High FG compatibility
Recyclable palladium catalyst
b
MKe Me i yna giLClzaomhb r orz nerc agsa tpi oC@o ranjyixd noi nfu gF. eudA nuuc .ttchinoo nr al Small Organic Molecule, Ministry of Education and College of Chemistry & Chemical Engineering, Jiangxi Normal University, Nanchang 330022, P. R. of China
Received: 03.10.2020
Accepted after revision: 10.11.2020
Published online: 13.01.2021
DOI: 10.1055/s-0040-1706621; Art ID: ss-2020-g0521-op
metal reagents, and have limited functional groups toler-
ance. Therefore, there has been a continuing quest for sim-
ple and efficient approaches.
Since the discovery of palladium-catalyzed carbonyla-
tion of aryl halides by Heck in 1974, the palladium-cata-
Abstract A magnetically recyclable palladium-catalyzed formylation
of aryl iodides under CO gas-free conditions has been developed by us-
ing a bidentate phosphine ligand-modified magnetic nanoparticles-
anchored palladium(II) complex [2P-Fe O @SiO -Pd(OAc) ] as catalyst,
yielding a wide variety of aromatic aldehydes in moderate to excellent
yields. Here, formic acid was employed as both the CO source and the
hydrogen donor with iodine and PPh3 as the activators. This immobi-
lized palladium catalyst can be obtained via a simple preparative proce-
dure and can be facilely recovered simply by using an external magnetic
field, and reused at least 9 times without any apparent loss of catalytic
activity.
5
lyzed formylation of aryl halides with carbon monoxide has
been developed into an alternative and more efficient route
3
4
2
2
6
to aryl aldehydes, and has been widely employed to con-
7
struct carbonyl-containing compounds. However, labora-
torial use of CO gas suffers from transportation, handling,
storage, and safety regulations due to its high toxicity and
flammable characters. For reasons of safety and operation,
a variety of CO surrogates have been extensively utilized in
palladium-catalyzed reductive carbonylation of aryl halides
Key words formylation, palladium, magnetic nanoparticles, hetero-
geneous catalysis, aromatic aldehyde
8
towards aryl aldehydes, including N-formylsaccharin, para-
9
10
formaldehyde, 9-methylfluorene-9-carbonyl chloride,
1
1
12
13
14
acetic formic anhydride, formic acid, Fe(CO)5, CO2, S-
1
5
16
Aromatic aldehydes are a class of important chemical
phenyl thioformate, and isocyanide. Although these pal-
ladium-catalyzed formylations of aryl halides under CO gas-
free conditions are highly efficient for the synthesis of aro-
matic aldehydes, in almost all cases homogeneous palladi-
um complexes such as Pd(OAc) /BuPAd , PdCl (dppp),
intermediates that are widely employed for the synthesis of
chemical materials, pharmaceuticals, pesticides, food addi-
1
tives, and so on. The conventional methods for the prepa-
ration of aromatic aldehydes involve an electrophilic formy-
lation of electron-rich aromatic rings including Gatter-
mann–Koch reaction, Reimer–Tiemann reaction, Vilsmeier
reaction, and Duff reaction, which generally suffer from
some inherent drawbacks such as the use of high amounts
of reagents and formation of wastes and by-products, mul-
tiple steps, low yields and/or poor selectivity as well as the
2
2
2
Pd(OAc) /dppb, and Pd(MeCN) Cl /dppb were used as the
2
2
2
catalysts, which suffered from the high cost, difficulty with
separation and non-recyclability of the palladium catalysts
as well as palladium contamination of the desired product
due to palladium leaching, thereby restricting their applica-
tions in large-scale synthesis or in industry. Therefore, the
development of an efficient, economic, and practical route
to aromatic aldehydes is highly desirable.
Anchoring homogeneous palladium catalysts through
covalent bond formation onto a solid support is one of the
most effective ways to solve these problems. The employ-
ment of the immobilized catalysts could result in conve-
nient separation, recovery, and recycle of the palladium cat-
alysts, thereby preventing contamination of the desired
2
incompatibility of many functional groups. In addition,
some other synthetic routes such as the reduction of aro-
3
matic carboxylic acids or esters and the direct formylation
of aryl halides via a halogen/lithium exchange followed by
4
addition of formylating agents are also well represented.
But these approaches usually require low reaction tempera-
tures and a stoichiometric amount of reductive agents or
©
2021. Thieme. All rights reserved. Synthesis 2021, 53, A–I
Georg Thieme Verlag KG, Rüdigerstraße 14, 70469 Stuttgart, Germany

B
Synthesis
S. You et al.
Paper
product from palladium and minimizing waste derived
from reaction workup.17 The use of magnetic nanoparticles
as the support is particularly attractive in this regard be-
cause the catalysts anchored onto magnetic nanoparticles
can be facilely separated and recovered from the product
simply by using an external magnetic field, which avoids
filtration or centrifugal operation, thereby effectively pre-
venting loss of catalyst and greatly improving the recy-
of 2P-Fe O @SiO -Pd(OAc) , which shows the excellent dis-
3
4
2
2
persion of the palladium sites on the magnetic nanoparti-
cles. These results indicate that the bidentate phosphine-
palladium complex has been successfully anchored onto the
magnetic nanoparticles.
PPh
PPh
2
(EtO) Si
3
N
2
O
O
PPh
2
Fe
SiO
@SiO
2
3
O
4
33 44
Fe O
Si
N
toluene, 110 °C, 48 h
SiO
2
PPh2
1
8
2
clability. During recent years, some functionalized mag-
netic nanoparticles-anchored palladium complexes have
been successfully utilized as recyclable catalysts in various
carbon–carbon coupling reactions.19 Very recently, we re-
ported the synthesis of a bidentate phosphine ligand-modi-
fied magnetic nanoparticles-anchored palladium(II) com-
plex [2P-Fe O @SiO -Pd(OAc) ] and its catalytic behavior in
OEt
P-Fe
Fe
3
O
4
2
3 4 2
O @SiO
PPh
2
Pd(OAc)
2
O
F ee 33
O
44
Si
N
Pd(OAc)
2
acetone, reflux, 48 h
SiO2
O
PPh2
OEt
2
3 4 2 2
P-Fe O @SiO -Pd(OAc)
Scheme 2 Preparation of the 2P-Fe O @SiO -Pd(OAc) complex
3
4
2
2
3
4
2
2
Heck coupling polycondensation of bis(acrylamide)s with
aromatic diiodides towards polycinnamamides.20 To extend
the application of this supported palladium catalyst, we
herein report a recyclable palladium-catalyzed formylation
of aryl iodides by using 2P-Fe O @SiO -Pd(OAc) as the het-
3
4
2
2
erogeneous catalyst with formic acid as both the CO source
and the hydrogen donor in the presence of iodine and PPh3
as the activators (Scheme 1). This heterogeneous formyla-
tion reaction proceeded smoothly under CO gas-free condi-
tions, delivering a wide variety of aryl aldehydes in moder-
ate to excellent yields with high functional group tolerance
and easy recycle of the palladium catalyst.
2
P-Fe3O4@SiO2-Pd(OAc)2
3 mol%)
O
(
Ar
I
+
HCOOH
I2, PPh3, Et3N, toluene, 80 °C
Ar
H
Figure 1 FT-IR spectra of Fe O @SiO (a) and 2P-Fe O @SiO -Pd(OAc) (b)
3
4
2
3
4
2
2
Scheme 1 Heterogeneous palladium-catalyzed formylation of aryl
iodides with HCOOH as CO source
The bidentate phosphine ligand-modified magnetic
nanoparticles-anchored palladium(II) complex [2P-
Fe O @SiO -Pd(OAc) ] was prepared by referring to our pre-
3
4
2
2
20
viously reported route as depicted in Scheme 2. The silica-
coated magnetic nanoparticles (Fe O @SiO ) was reacted
3
4
2
with
N,N-bis[(diphenylphosphino)methyl]-3-(triethoxy-
silyl)propan-1-amine in anhydrous toluene at 110 °C for 48
hours to give the bidentate phosphine ligand-modified
magnetic nanoparticles (2P-Fe O @SiO ). The 2P-Fe O @SiO
2
3
4
2
3
4
was then complexed with palladium acetate in acetone at
reflux for 48 hours to furnish the bidentate phosphine li-
gand-modified magnetic nanoparticles-anchored palladi-
um(II) complex [2P-Fe O @SiO -Pd(OAc) ]. Figure 1 shows
3
4
2
2
the FT-IR spectra of Fe O @SiO (a) and 2P-Fe O @SiO -
Figure 2 XRD patterns of Fe O @SiO (a) and 2P-Fe O @SiO -Pd(OAc) (b)
3 4 2 3 4 2 2
3
4
2
3
4
2
Pd(OAc)2 (b). In the FT-IR spectrum of 2P-Fe O @SiO -
3
4
2
–
1
Pd(OAc) , absorptions at 2924 cm (CH ), 1605 and 1559
2
2
–
1
cm (benzene ring) were observed indicating the presence
of silylated phosphine-palladium groups. The XRD patterns
of Fe O @SiO (a) and 2P-Fe O @SiO -Pd(OAc) (b) are
The 2P-Fe O @SiO -Pd(OAc) complex was then utilized
3
4
2
2
as the catalyst for the formylation of aryl iodides by using
HCOOH as both the CO source and the hydrogen donor in
3
4
2
3
4
2
2
presented in Figure 2. No peaks characteristic for palladi-
um(0) nanoparticles were observed from the XRD pattern
the presence of iodine and PPh as the activators. Initially,
3
©
2021. Thieme. All rights reserved. Synthesis 2021, 53, A–I

C
Synthesis
S. You et al.
Paper
the formylation of 4-iodoanisole with HCOOH was chosen
as the model reaction to determine the optimal reaction
conditions including solvents, bases, reaction temperatures,
and catalyst loadings. The results are summarized in Table
para- or meta-substituted ones and produced the corre-
sponding aromatic aldehydes 2u–x in 67–80% yields on a
longer reaction time. Furthermore, highly sterically con-
gested 2,6-disubstituted iodobenzenes 1y and 1z could also
undergo the formylation effectively to give the target prod-
ucts 2y and 2z in 63–68% yields. It is also noteworthy that
aryl iodides bearing active functional groups 1a′–e′ under-
went the formylation smoothly to give the functionalized
aryl aldehydes 2a′–e′ in 75–88% yields. In addition to aryl
iodides, heteroaryl iodides such as 3-iodopyridine, 2-iodo-
thiophene, and 2-iodofuran were also compatible in this re-
action and provided the corresponding heteroaryl alde-
hydes 2f′–h′ in 61–71% yields. A wide variety of functional
groups such as methyl, methoxy, acetyloxy, dimethylamino,
fluoro, chloro, bromo, trifluoromethyl, ester, ketone, cyano,
1
. At first, the effect of various bases on the model reaction
was evaluated in toluene as the solvent at 80 °C in the pres-
ence of I (1.2 equiv) and PPh (1.2 equiv) as the activators
2
3
(
Table 1, entries 1–7). The use of DIPEA, DBU, Et N, or TMEDA
3
as the base afforded the desired 2a in 62–86% yields and
Et N gave the best result (entry 5), while DABCO, DMAP,
3
and K CO proved to be ineffective (entries 3, 4, and 7). Re-
2
3
placement of toluene with THF, MeCN, DMF, DCM, or 1,4-
dioxane resulted in a decreased yield of 2a (entries 8–12),
so toluene as solvent was the best option in this transfor-
mation (entry 5). Further examination of reaction tempera-
tures showed that lowering the temperature to 70 °C led to
a decreased yield, whilst raising the temperature to 90 or
Table 1 Optimization of the Reaction Conditionsa
1
00 °C did not enhance the yield of 2a (entries 13–15).
When the amounts of HCOOH or Et N were further in-
creased, no improvement in the yield of 2a was observed
3
O
2
P-Fe3O4@SiO2-Pd(OAc)2
3 mol%)
I
(
H
+
HCOOH
(
entries 16 and 17). Also, the amounts of the palladium cat-
I2 (1.2 equiv), PPh3 (1.2 equiv)
base, solvent, temp
MeO
MeO
alyst were tested. Reducing the amount of the catalyst to 1
mol% lowered the yield of 2a to 62% and needed a long reac-
tion time (12 h, entry 18). Increasing the amount of the cat-
alyst to 5 mol% could enhance the reaction rate, but the re-
action did not give an increased yield (entry 19). The use of
1
a
2a
Entry
Solvent
Base
DIPEA
Temp (°C)
Yield (%)b
1
2
toluene
toluene
toluene
toluene
toluene
toluene
toluene
THF
80
80
80
80
80
80
80
80
80
80
80
80
70
90
100
80
80
80
80
80
78
62
0
DBU
homogeneous Pd(OAc) (3 mol%) as the catalyst also fur-
2
3
DABCO
DMAP
nished the desired 2a in 87% yield (entry 20), which indi-
cated that the catalytic efficiency of 2P-Fe O @SiO -
4
0
3
4
2
Pd(OAc)2 was comparable to that of Pd(OAc) . Thus, the
2
5
Et
TMEDA
CO
3
N
86
67
0
optimized reaction conditions were established as
6
2
P-Fe O @SiO -Pd(OAc) (3 mol%), HCOOH (4 equiv), Et N
3 4 2 2 3
7
K
2
3
(
6 equiv), I (1.2 equiv), and PPh (1.2 equiv) in toluene at
2
3
8
Et
Et
3
3
N
N
60
65
53
74
57
59
85
86
86
85
62
86
87
8
0 °C for 3 hours (entry 5).
9
MeCN
With the optimized conditions in hand, we next ex-
plored the generality and scope of this heterogeneous
formylation reaction with a wide variety of aryl iodides.
The results are shown in Scheme 3. As depicted in Scheme
10
DMF
3
Et N
1
1
1
1
1
2
3
4
DCM
Et
Et
Et
Et
Et
3
3
3
3
3
N
N
N
N
N
1,4-dioxane
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
3
, iodobenzene (1b) and a wide variety of substituted iodo-
benzenes 1c–r underwent the heterogeneous formylation
smoothly under the optimal conditions to give the corre-
sponding aromatic aldehydes 2b–r in 56–93% yields. For ex-
ample, various para- or meta-substituted electron-rich aryl
iodides 1c–h afforded the desired products 2c–h in 79–87%
yields. Aryl iodides with weak electron-withdrawing sub-
stituents 1i–m delivered various halosubstituted aryl alde-
hydes 2i–m in 74–93% yields. Notably, aryl iodides bearing
strong electron-withdrawing groups 1n–r, which are tradi-
tionally considered as forbidden substrates in this type of
conversion also reacted well, thereby furnishing the expect-
ed products 2n–r in 56–77% yields. In addition, bulky 1-io-
donaphthalene (1s) and 2-iodonaphthalene (1t) gave the
desired naphthyl aldehydes 2s and 2t in 71 and 74% yield,
respectively. Sterically hindered ortho-substituted iodoben-
zenes 1u–x displayed a relatively lower reactivity than the
15
16c
3
Et N
7d
1
1
1
Et
Et
Et
Et
3
3
3
3
N
N
N
N
8e
9f
2
0g
a
Reaction conditions: 1a (1 mmol), HCOOH (4 mmol), I
1.2 mmol), base (6 mmol), 2P-Fe @SiO -Pd(OAc) (3 mol%), solvent
4 mL), 3 h.
2 3
(1.2 mmol), PPh
(
(
3
O
4
2
2
b
c
d
e
f
Isolated yield.
HCOOH (6 mmol) was used.
3
N (8 mmol) was used.
Et
2P-Fe O @SiO -Pd(OAc) (1 mol%) was used for 12 h.
3
4
2
2
2
P-Fe
Pd(OAc)
3
O
4
@SiO
2 2
-Pd(OAc) (5 mol%) was used for 2 h.
(3 mol%) was used for 2 h.
g
2
©
2021. Thieme. All rights reserved. Synthesis 2021, 53, A–I

D
Synthesis
S. You et al.
Paper
nitro, hydroxy, and carboxy were tolerated well in this
transformation. Encouraged by the above results, we also
performed the formylation of aryl bromides with HCOOH
under the optimized conditions, unfortunately, the formy-
lation reaction did not occur at all even at elevated tem-
peratures, which may be due to the fact that oxidative addi-
tion of aryl bromides to a heterogeneous palladium com-
plex did not take place. So, substrates 1l–m and 1w could
be chemoselectively converted into the corresponding bro-
mo-substituted aryl aldehydes in good yields.
desired o-phthalaldehyde (4a) in low yield of 12%, probably
owing to the interference of palladium oxidative addition
by the neighboring carbonyl group, and 2-iodobenzalde-
hyde was isolated as a by-product in 34% yield. To our de-
light, 1,3-diiodobenzene (3b) and 1,4-diiodobenzene (3c)
could undergo the diformylation smoothly to afford isoph-
thalaldehyde (4b) and terephthalaldehyde (4c) in 75 and
53% yield, respectively.
I
CHO
I
CHO
2
P-Fe3O4@SiO2-Pd(OAc)2
3 mol%)
3a
4
a, 12%
O
3 4 2
2P-Fe O @SiO -Pd(OAc)
(
2
I
I
Ar
I
+
HCOOH
(6 mol%)
OHC
CHO
CHO
I2 (1.2 equiv), PPh3 (1.2 equiv)
Et3N, toluene, 80 °C
Ar
H
+
HCOOH
(8 equiv)
I
2
(2.4 equiv), PPh
3
(2.4 equiv)
1
2
3
b
Et
3
N (12 equiv), toluene, 80 °C, 6 h
4b, 75%
4c, 53%
O
O
O
O
I
Me
H
H
H
H
I
OHC
MeO
MeO
Me
H
3c
2
a, 86%
2b, 91%
2c, 84%
2d, 81%
O
O
O
MeO
Scheme 4 Heterogeneous palladium-catalyzed diformylation of aro-
matic diiodides with HCOOH
O
H
H
Me
H
O
O
Me2N
2
e, 79%
2f, 83%
2g, 87%
MeO 2h, 77%
O
O
O
O
To identify whether the observed formylation was due
to the heterogeneous 2P-Fe O @SiO -Pd(OAc) complex or a
Cl
H
H
H
H
3
4
2
2
F
Cl
Br
leached palladium species from this catalyst, we performed
2
i, 74%
2j, 91%
2k, 93%
2l, 81%
2p, 68%
21
O
O
O
O
O
the hot filtration test. For this, the formylation of 4-iodo-
anisole (1a) was conducted until a conversion of 60%. The
palladium catalyst was then separated magnetically from
the reaction solution at 80 °C and the solution was trans-
ferred into another reaction tube. After the addition of I2
Br
H
H
H
H
H
MeO
Me
F3C
O
O
2
m, 83%
2n, 77%
2o, 71%
O
O
O
H
H
H
(
0.6 equiv), PPh (0.6 equiv), HCOOH (2 equiv), and Et N (3
3
3
NC
O2N
equiv), the catalyst-free solution was stirred at 80 °C for an-
other 3 hours. In this case, further increase in conversion of
2
q, 65%
2r, 56%
2s, 71%
2t, 74%
Me
O
OMe
Br
Cl
O
O
O
4
-iodoanisole (1a) was not observed, indicating that the
H
H
H
H
soluble palladium species leached from 2P-Fe O @SiO -
3
4
2
Cl
2
u, 72%
2v, 67%
2w, 78%
2x, 80%
Pd(OAc)2 was not responsible for the observed reductive
carbonylation. Furthermore, ICP-AES analysis of the reac-
tion solution showed that no palladium species could be
detected (below the detection limit). These results indicate
that the 2P-Fe O @SiO -Pd(OAc) complex was stable
Me
O
F
O
OH
O
O
HO
H
H
H
H
H
Me
F
2
y, 68%
2z, 63%
2a', 78%
2b', 88%
O
O
O
O
3
4
2
2
HO2C
H
H
H
during the formylation and the nature of the reaction was
heterogeneous.
HO
HO2C
N
2
c', 83%
2d', 81%
2e', 75%
2f', 71%
A plausible reaction mechanism for this heterogeneous
palladium-catalyzed formylation of aryl iodides with
HCOOH is illustrated in Scheme 5. First, I and PPh form the
O
O
S
O
H
H
2
3
2
g', 63%
2h', 61%
complex A, which can trigger the release of CO from
Scheme 3 Heterogeneous palladium-catalyzed formylation of aryl
iodides with HCOOH. Reagents and conditions: 1 (1 mmol), HCOOH
4 mmol), I (1.2 mmol), PPh (1.2 mmol), Et N (6 mmol),
HCOOH. Then the 2P-Fe O @ SiO -Pd(OAc) complex is easi-
3
4
2
2
ly reduced by CO to 2P-Fe O @SiO -Pd(0). Oxidative addi-
3
4
2
(
2
2
3
3
tion of Ar-I 1 to 2P-Fe O @SiO -Pd(0) generates a magnetic
3
4
2
P-Fe O @SiO -Pd(OAc) (3 mol%), toluene (4 mL), 80 °C, 3 h. Isolated
3 4 2 2
nanoparticle-bound arylpalladium(II) complex B, which is
followed by migratory insertion of CO to give a magnetic
nanoparticles-bound acylpalladium(II) complex C. Subse-
quent reaction between intermediate C and HCOOH with
yields are shown. For 2n–r: The reaction was conducted at 70 °C.
Reaction time for 2s–z,a′: 5 h.
In order to expand application of this methodology, aro-
matic diiodides were used as substrates to perform the di-
formylation reaction (Scheme 4). It was found that 1,2-
diiodobenzene (3a) displayed poor reactivity, providing the
the aid of Et N produces a magnetic nanoparticles-bound
3
acylpalladium(II) formic acid complex intermediate D and
releases HI simultaneously. Finally, intermediate D under-
©
2021. Thieme. All rights reserved. Synthesis 2021, 53, A–I

E
Synthesis
S. You et al.
Paper
goes decarboxylation and reductive elimination to afford
the desired aryl aldehyde 2 and regenerates the 2P-
Fe O @SiO -Pd(0) complex that launches next catalytic cy-
ability of the 2P-Fe O @SiO -Pd(OAc) catalyst might arise
from the chelating action of the bidentate phosphine ligand
on the palladium center.
3
4
2
2
3
4
2
cle.
a
Table 2 Recycle of the 2P-Fe O @SiO -Pd(OAc) Catalyst
3
4
2
2
2
P-Fe3O4@SiO2-Pd(OAc)2
CO
I2
+
PPh3
O
2
P-Fe3O4@SiO2-Pd(OAc)2
3 mol%)
I
trigger
Cl
Cl
(
O
H
Fe3O4@SiO2
+
HCOOH
+
CO2
I2 (1.2 equiv), PPh3 (1.2 equiv)
Et3N, toluene, 80 °C, 3 h
Ar
H
I
[I-PPh3]
A
2
Ar-I
1k
2k
HCOOH
1
P
P
HCOO [I-PPh3]
Entry
Catalyst
fresh
Yield (%)b Entry
Catalyst
Yield (%)b
Pd(0)
Fe3O4@SiO2
1
2
3
4
93
92
93
93
92
6
7
recycle 5
recycle 6
recycle 7
recycle 8
recycle 9
91
90
91
89
89
Fe3O4@SiO2
I
[HCOO-PPh3]
recycle 1
recycle 2
recycle 3
recycle 4
HI + Ph3PO
P
P
D
8
P
P
B
O
Pd(II)
9
Ar
Pd(II)
O
H
Ar
O
I
5
10
Fe3O4@SiO2
a
Reaction conditions: 1k (1 mmol), HCOOH (4 mmol), I
1.2 mmol), Et N (6 mmol), 2P-Fe @SiO -Pd(OAc) (3 mol%), toluene
(4 mL), 80 °C, 3 h.
Isolated yield.
2 3
(1.2 mmol), PPh
(
3
3
O
4
2
2
Et3N•HI
CO
P
P
C
b
Et3N•HCOOH
Pd(II)
Ar
I
O
Scheme 5 Proposed catalytic cycle
For the application of a heterogeneous palladium cata-
lyst in the large-scale synthesis or in industry, its ease of
separation from the product and the ability to recycle it are
significant factors that need to be examined. We next eval-
uated the recyclability of the palladium catalyst in the
formylation reaction of 3-chloroiodobenzene (1k) with
HCOOH under the standard conditions and the results are
listed in Table 2. Upon completion of the first reaction cycle,
the reaction mixture was cooled to room temperature. As
expected, more than 99% of the palladium catalyst could be
facilely recovered simply by fixing a magnet to the outside
of the reaction tube. The recovered palladium catalyst was
washed with toluene, distilled water and ethanol, dried un-
der vacuum at 80 °C, and used directly in the next cycle. As
seen from Table 2, the yield of the desired product 2k in ten
consecutive cycles was over 89%, which reveals that this
heterogeneous palladium catalyst can be reused at least
nine times with only a slight drop in catalytic efficiency.
Figure 3 shows TEM images of the fresh catalyst (a) and the
recovered catalyst after ten cycles (b). No obvious differenc-
es in the morphology and dispersion of particles were ob-
served from their TEM images, which show that the struc-
tural regularity of the recovered catalyst is consistent with
the fresh catalyst. In addition, the palladium leaching in this
supported Pd catalyst was also examined and the Pd con-
tent of the recovered catalyst after ten consecutive cycles
was measured to be 0.37 mmol/g by ICP-AES analysis, re-
vealing a negligible palladium leaching. The excellent reus-
Figure 3 TEM images of the fresh catalyst (a) and the recovered cata-
lyst after ten cycles (b)
In summary, we have developed a novel, facile, and
practical method for the synthesis of aromatic aldehydes
through a heterogeneous palladium-catalyzed formylation
of aryl iodides with dual-role HCOOH by using a bidentate
phosphine ligand-modified magnetic nanoparticles-an-
chored palladium(II) complex [2P-Fe O @SiO -Pd(OAc) ] as
3
4
2
2
catalyst under CO gas-free conditions. In contrast to the
conventional route to aromatic aldehydes, this heteroge-
neous formylation strategy has some attractive features,
such as: (1) the scope of substrates is broad, and a wide
range of aryl iodides are allowed; (2) a wide variety of aro-
matic aldehydes are obtained in moderate to excellent
yields under mild conditions; (3) the reaction avoids the
use of CO gas and additional reductant; (4) many functional
groups including active hydroxy and carboxy are well toler-
ated; and (5) this heterogeneous palladium catalyst can be
facilely recovered simply by fixing a magnet to the outside
of the reaction tube and recycled up to ten times without
any apparent decrease in catalytic activity. Thus, the cur-
rent methodology is an attractive alternative to synthesize
aromatic aldehydes.
©
2021. Thieme. All rights reserved. Synthesis 2021, 53, A–I

F
Synthesis
S. You et al.
Paper
Benzaldehyde (2b)12c
All starting materials were purchased from various commercial
sources and used as received without further purification. All sol-
vents were dried and distilled prior to use. The silica-coated magnetic
Yield: 96.6 mg (91%); colorless oil.
1
H NMR (400 MHz, CDCl ):  = 10.00 (s, 1 H), 7.88–7.85 (m, 2 H), 7.63–
3
1
9f
Fe O4 nanoparticles (Fe O @SiO ) and N,N-bis[(diphenylphosphi-
3
3
4
2
7.59 (m, 1 H), 7.51 (t, J = 7.6 Hz, 2 H).
2
2
no)methyl]-3-(triethoxysilyl)propan-1-amine were prepared by re-
ferring to literature procedures. The products were purified by silica
gel column chromatography with a mixture of light petroleum ether
1
3
C NMR (100 MHz, CDCl ):  = 192.3, 136.4, 134.4, 129.7, 129.0.
3
4-Methylbenzaldehyde (2c)12c
1
13
(
PE) and EtOAc as eluent. H NMR (400 MHz) and C NMR (100 MHz)
spectra were obtained on a Bruker Avance 400 NMR spectrometer in
Yield: 100.9 mg (84%); colorless oil.
CDCl as solvent with TMS as internal reference. Melting points were
1
3
H NMR (400 MHz, CDCl ):  = 9.94 (s, 1 H), 7.76 (d, J = 8.4 Hz, 2 H),
3
measured on a Beijing Tech Instrument Co., LTD X-6 melting point ap-
paratus and are uncorrected. Pd content was measured on a Jarrell-
Ash 1100 ICP. FT-IR spectra were obtained with a Horiba FT-720 FTIR
spectrophotometer. X-ray diffraction (XRD) patterns were recorded at
r.t. on a Rigaku D/MAX-IIA X-ray diffractometer with nickel-filtered
CuK radiation (40 KV and 20 mA). TEM images were recorded in a
transmission electron microscope operated at an accelerated voltage
of 200 kV.
7
.31 (d, J = 7.6 Hz, 2 H), 2.41 (s, 3 H).
1
3
C NMR (100 MHz, CDCl ):  = 192.0, 145.6, 134.2, 129.8, 129.7, 21.8.
3
3
-Methylbenzaldehyde (2d)12c
Yield: 97.4 mg (81%); colorless oil.
1
H NMR (400 MHz, CDCl ):  = 9.96 (s, 1 H), 7.68–7.63 (m, 2 H), 7.43–
3
7
.37 (m, 2 H), 2.40 (s, 3 H).
1
3
C NMR (100 MHz, CDCl ):  = 192.5, 138.9, 136.5, 135.3, 130.0,
3
2
P-Fe O @SiO -Pd(OAc)
3 4 2 2
1
28.9, 127.2, 21.1.
A mixture of Fe O @SiO (1.12 g) and N,N-bis[(diphenylphosphi-
3
4
2
no)methyl]-3-(triethoxysilyl)propan-1-amine (0.928 g, 1.5 mmol) in
anhyd toluene (50 mL) was stirred at 110 °C under argon atmosphere
for 48 h. The resulting product was then magnetically separated, fol-
lowed by washing with toluene (2 × 15 mL) and dried in vacuo at 120
-Methoxybenzaldehyde (2e)12c
3
Yield: 107.6 mg (79%); colorless oil.
1H NMR (400 MHz, CDCl
):  = 9.97 (d, J = 0.8 Hz, 1 H), 7.47–7.43 (m, 2
H), 7.40–7.38 (m, 1 H), 7.20–7.16 (m, 1 H), 3.86 (d, J = 0.8 Hz, 3 H).
3
°C for 4 h to furnish 1.327 g of the bidentate phosphine ligand-modi-
fied Fe O @SiO (2P-Fe O @SiO ). The phosphorus content of 2P-
13
3
4
2
3
4
2
C NMR (100 MHz, CDCl ):  = 192.1, 160.2, 137.8, 130.0, 123.5,
3
–
1
Fe O @SiO was measured to be 0.97 mmol g by elemental analysis.
3
4
2
121.5, 112.1, 55.5.
A mixture of 2P-Fe O @SiO (1.08 g) and Pd(OAc) (91 mg, 0.4 mmol)
3
4
2
2
4-Acetyloxybenzaldehyde (2f)23
in anhyd acetone (50 mL) was stirred at reflux under argon atmo-
sphere for 48 h. After cooling to r.t., the solid product was magnetical-
ly separated from the solution, followed by washing with distilled wa-
ter (2 × 15 mL) and acetone (15 mL), and dried in vacuo at 70 °C for 6 h
to afford 1.064 g of 2P-Fe O @SiO -Pd(OAc) . The palladium content
Yield: 136.3 mg (83%); colorless oil.
1
H NMR (400 MHz, CDCl ):  = 9.95 (s, 1 H), 7.88 (d, J = 8.8 Hz, 2 H),
3
7
.25 (d, J = 8.4 Hz, 2 H), 2.30 (s, 3 H).
3
4
2
2
of 2P-Fe O @SiO -Pd(OAc) was determined to be 0.38 mmol g–1
13C NMR (100 MHz, CDCl
122.3, 21.0.
):  = 191.0, 168.6, 155.3, 133.9, 131.1,
3
3
4
2
2
based on ICP-AES analysis.
4-Dimethylaminobenzaldehyde (2g)12d
Heterogeneous Palladium-Catalyzed Formylation of Aryl Iodides
with HCOOH; General Procedure
Yield: 129.8 mg (87%); white solid; mp 73–75 °C.
A dried 10 mL reaction tube was charged with I (152 mg, 1.2 mmol),
1
2
H NMR (400 MHz, CDCl ):  = 9.73 (s, 1 H), 7.73 (d, J = 8.8 Hz, 2 H),
3
PPh (315 mg, 1.2 mmol), and toluene (4 mL) under argon. The mix-
3
6.70 (d, J = 8.8 Hz, 2 H), 3.08 (s, 6 H).
1
ture was stirred at r.t. for 10 min. Then aryl iodide 1 (1 mmol), 2P-
3
C NMR (100 MHz, CDCl ):  = 190.3, 154.4, 132.0, 125.2, 111.0, 40.1.
3
Fe O @SiO -Pd(OAc) (79 mg, 3 mol%), and Et N (606 mg, 6 mmol)
3
4
2
2
3
were added to this solution. After the addition of HCOOH (184 mg, 4
mmol), the reaction tube was immediately sealed and the reaction
mixture was stirred at 80 °C for 3–5 h. After cooling to r.t., the Pd cat-
alyst was magnetically separated from the mixture, washed with tol-
3
,5-Dimethoxybenzaldehyde (2h)24
Yield: 127.9 mg (77%); white solid; mp 45–46 °C.
1
H NMR (400 MHz, CDCl ):  = 9.90 (s, 1 H), 7.01 (d, J = 2.0 Hz, 2 H),
3
uene (2 mL), distilled H O (2 × 2 mL) and EtOH (2 × 2 mL), dried under
2
6.70 (s, 1 H), 3.84 (s, 6 H).
vacuum at 80 °C, and used directly in the next cycle. The reaction
mixture was then filtered and concentrated under vacuum. The resi-
due was purified by silica gel column chromatography (light PE/EtOAc
1
3
C NMR (100 MHz, CDCl ):  = 191.9, 161.3, 138.4, 107.2, 107.1, 55.6.
3
4
-Fluorobenzaldehyde (2i)12c
10:1) to afford the desired product 2.
Yield: 91.8 mg (74%); colorless oil.
-Methoxybenzaldehyde (2a)12c
1
H NMR (400 MHz, CDCl ):  = 9.97 (s, 1 H), 7.94–7.90 (m, 2 H), 7.24–
4
3
7
.19 (m, 2 H).
Yield: 118.2 mg (86%); colorless oil.
1
3
1
C NMR (100 MHz, CDCl ):  = 190.5, 166.5 (d, J = 255.2 Hz), 133.0 (d,
3
H NMR (400 MHz, CDCl ):  = 9.85 (d, J = 2.0 Hz, 1 H), 7.82–7.78 (m, 2
3
J = 2.7 Hz), 132.2 (d, J = 9.7 Hz), 116.3 (d, J = 22.1 Hz).
H), 6.99–6.95 (m, 2 H), 3.84 (t, J = 2.2 Hz, 3 H).
1
3
C NMR (100 MHz, CDCl ):  = 190.6, 164.5, 131.8, 129.9, 114.3, 55.5.
3
4
-Chlorobenzaldehyde (2j)12c
Yield: 128.6 mg (91%); white solid; mp 47–48 °C.
©
2021. Thieme. All rights reserved. Synthesis 2021, 53, A–I

G
Synthesis
S. You et al.
Paper
1
1
H NMR (400 MHz, CDCl ):  = 9.99 (s, 1 H), 7.83 (d, J = 8.4 Hz, 2 H),
H NMR (400 MHz, CDCl ):  = 10.18 (s, 1 H), 8.41 (d, J = 8.8 Hz, 2 H),
3
3
7.52 (d, J = 8.4 Hz, 2 H).
8.10 (d, J = 8.8 Hz, 2 H).
1
3
13
C NMR (100 MHz, CDCl ):  = 190.8, 141.0, 134.7, 130.9, 129.5.
C NMR (100 MHz, CDCl ):  = 190.3, 151.1, 140.1, 130.5, 124.3.
3
3
3
-Chlorobenzaldehyde (2k)12c
1-Naphthaldehyde (2s)12a
Yield: 130.7 mg (93%); colorless oil.
Yield: 110.9 mg (71%); colorless oil.
1
1
H NMR (400 MHz, CDCl ):  = 9.97 (s, 1 H), 7.85 (t, J = 2.0 Hz, 1 H),
H NMR (400 MHz, CDCl ):  = 10.28 (t, J = 4.0 Hz, 1 H), 9.20 (d, J = 8.4
3
3
7.78–7.75 (m, 1 H), 7.61–7.58 (m, 1 H), 7.48 (t, J = 7.8 Hz, 1 H).
Hz, 1 H), 7.93 (d, J = 8.0 Hz, 1 H), 7.84–7.76 (m, 2 H), 7.61–7.56 (m, 1
1
3
H), 7.51–7.43 (m, 2 H).
C NMR (100 MHz, CDCl ):  = 190.9, 137.8, 135.4, 134.4, 130.4,
3
1
3
1
29.3, 128.0.
C NMR (100 MHz, CDCl ):  = 193.5, 136.7, 135.3, 133.7, 131.3,
3
1
30.5, 129.1, 128.5, 127.0, 124.9.
4
-Bromobenzaldehyde (2l)12c
2
-Naphthaldehyde (2t)12d
Yield: 149.8 mg (81%); light yellow solid; mp 57–58 °C.
1
Yield: 115.6 mg (74%); pale yellow solid; mp 59–60 °C.
H NMR (400 MHz, CDCl ):  = 9.98 (s, 1 H), 7.76–7.73 (m, 2 H), 7.70–
.67 (m, 2 H).
3
1
7
H NMR (400 MHz, CDCl ):  = 10.15 (s, 1 H), 8.32 (s, 1 H), 7.99 (d, J =
3
1
3
8.0 Hz, 1 H), 7.96–7.87 (m, 3 H), 7.66–7.55 (m, 2 H).
C NMR (100 MHz, CDCl ):  = 191.1, 135.1, 132.4, 131.0, 129.8.
3
1
3
C NMR (100 MHz, CDCl ):  = 192.2, 136.5, 134.5, 134.2, 132.7,
3
-Bromobenzaldehyde (2m)24
129.5, 129.1, 128.1, 127.1, 122.8.
3
Yield: 153.6 mg (83%); colorless oil.
2
-Methylbenzaldehyde (2u)12c
1
H NMR (400 MHz, CDCl ):  = 9.95 (d, J = 2.4 Hz, 1 H), 7.98 (d, J = 1.6
3
Yield: 86.5 mg (72%); colorless oil.
Hz, 1 H), 7.80 (dd, J = 7.6, 0.8 Hz, 1 H), 7.75–7.71 (m, 1 H), 7.44–7.38
1
(m, 1 H).
H NMR (400 MHz, CDCl ):  = 10.26 (s, 1 H), 7.79 (dd, J = 7.6, 1.6 Hz, 1
3
1
3
H), 7.49–7.44 (m, 1 H), 7.37–7.33 (m, 1 H), 7.25 (d, J = 7.6 Hz, 1 H),
C NMR (100 MHz, CDCl ):  = 190.7, 138.0, 137.2, 132.3, 130.6,
3
2
.66 (s, 3 H).
1
28.4, 123.3.
1
3
C NMR (100 MHz, CDCl ):  = 192.8, 140.6, 134.1, 133.7, 132.1,
3
-(Trifluoromethyl)benzaldehyde (2n)12d
131.8, 126.3, 19.6.
4
Yield: 134.1 mg (77%); colorless oil.
2
-Methoxybenzaldehyde (2v)12c
Yield: 91.3 mg (67%); colorless oil.
1H NMR (400 MHz, CDCl
):  = 10.47 (s, 1 H), 7.82 (dd, J = 7.8, 1.8 Hz, 1
H), 7.57–7.52 (m, 1 H), 7.04–7.01 (m, 1 H), 6.99 (d, J = 8.8 Hz, 1 H),
.92 (s, 3 H).
1
H NMR (400 MHz, CDCl ):  = 10.11 (s, 1 H), 8.02 (d, J = 8.0 Hz, 2 H),
3
7.82 (d, J = 8.4 Hz, 2 H).
1
3
3
C NMR (100 MHz, CDCl ):  = 191.0, 138.7, 135.6 (q, J = 32.5 Hz),
3
129.9, 126.1 (q, J = 3.7 Hz), 123.4 (q, J = 271.2 Hz).
3
1
3
Methyl 4-Formylbenzoate (2o)12d
C NMR (100 MHz, CDCl ):  = 189.8, 161.8, 136.0, 128.5, 124.8,
3
1
20.7, 111.7, 55.6.
Yield: 116.5 mg (71%); white solid; mp 60–62 °C.
1
H NMR (400 MHz, CDCl ):  = 10.11 (s, 1 H), 8.19 (dd, J = 8.2, 1.4 Hz, 2
3
-Bromobenzaldehyde (2w)24
2
H), 7.97–7.94 (m, 2 H), 3.96 (s, 3 H).
1
Yield: 144.3 mg (78%); colorless oil.
3
C NMR (100 MHz, CDCl ):  = 191.6, 166.0, 139.1, 135.1, 130.2,
3
1
H NMR (400 MHz, CDCl ):  = 10.32 (s, 1 H), 7.88–7.85 (m, 1 H), 7.62–
1
29.5, 52.6.
3
7
.59 (m, 1 H), 7.44–7.37 (m, 2 H).
1
3
-Acetylbenzaldehyde (2p)12d
C NMR (100 MHz, CDCl ):  = 191.7, 135.3, 133.8, 133.4, 129.8,
4
3
1
27.9, 127.0.
Yield: 100.7 mg (68%); white solid; mp 34–36 °C.
1
H NMR (400 MHz, CDCl ):  = 10.12 (s, 1 H), 8.11 (d, J = 8.4 Hz, 2 H),
.99 (d, J = 8.4 Hz, 2 H), 2.67 (s, 3 H).
3
,4-Dichlorobenzaldehyde (2x)25
2
7
1
Yield: 140.1 mg (80%); pale yellow solid; mp 65–67 °C.
3
C NMR (100 MHz, CDCl ):  = 197.4, 191.6, 141.2, 139.1, 129.8,
3
1
H NMR (400 MHz, CDCl ):  = 10.41 (s, 1 H), 7.87 (d, J = 8.4 Hz, 1 H),
1
28.8, 27.0.
3
7
.48 (d, J = 2.0 Hz, 1 H), 7.37 (dd, J = 8.2, 1.4 Hz, 1 H).
1
3
-Cyanobenzaldehyde (2q)12c
C NMR (100 MHz, CDCl ):  = 188.4, 141.1, 138.5, 131.0, 130.5,
4
3
1
30.3, 127.9.
Yield: 85.2 mg (65%); light yellow solid; mp 98–99 °C.
1
H NMR (400 MHz, CDCl ):  = 10.11 (s, 1 H), 8.01 (d, J = 8.0 Hz, 2 H),
.86 (d, J = 8.0 Hz, 2 H).
3
,6-Dimethylbenzaldehyde (2y)26
2
7
1
Yield: 91.3 mg (68%); colorless oil.
3
C NMR (100 MHz, CDCl ):  = 190.6, 138.8, 132.9, 129.9, 117.7,
3
1
H NMR (400 MHz, CDCl ):  = 10.61 (d, J = 1.6 Hz, 1 H), 7.31 (t, J = 7.6
1
17.6.
3
Hz, 1 H), 7.08 (d, J = 7.6 Hz, 2 H), 2.60 (s, 6 H).
1
3
-Nitrobenzaldehyde (2r)12c
C NMR (100 MHz, CDCl ):  = 193.5, 141.1, 133.0, 132.5, 129.7, 20.5.
3
4
Yield: 84.6 mg (56%); yellow solid; mp 104–105 °C.
©
2021. Thieme. All rights reserved. Synthesis 2021, 53, A–I

H
Synthesis
S. You et al.
Paper
2
,6-Difluorobenzaldehyde (2z)27
Furan-2-carbaldehyde (2h′)12c
Yield: 89.5 mg (63%); colorless oil.
Yield: 58.6 mg (61%); colorless oil.
1
1
H NMR (400 MHz, CDCl ):  = 10.36 (s, 1 H), 7.62–7.54 (m, 1 H), 7.01
H NMR (400 MHz, CDCl ):  = 9.67 (d, J = 0.8 Hz, 1 H), 7.72 (t, J = 0.8
3
3
(t, J = 8.6 Hz, 2 H).
Hz, 1 H), 7.28 (dd, J = 3.6, 0.8 Hz, 1 H), 6.62 (dd, J = 3.6, 1.6 Hz, 1 H).
1
3
13
C NMR (100 MHz, CDCl ):  = 184.5 (t, J = 4.5 Hz), 163.2 (dd, J =
C NMR (100 MHz, CDCl ):  = 177.9, 152.9, 148.1, 121.2, 112.6.
3
3
261.5, 5.6 Hz), 136.3 (t, J = 11.3 Hz), 114.2, 112.5 (dd, J = 22.5, 2.3 Hz).
Compounds 4a–c; General Procedure
2
-Hydroxybenzaldehyde (2a′)12c
A dried 20 mL reaction tube was charged with I (304 mg, 2.4 mmol),
2
Yield: 95.2 mg (78%); colorless oil.
PPh (630 mg, 2.4 mmol), and toluene (6 mL) under argon. The mix-
3
1
ture was stirred at r.t. for 10 min. Then aryl diiodide 3 (1 mmol), 2P-
H NMR (400 MHz, CDCl ):  = 11.02 (s, 1 H), 9.86 (s, 1 H), 7.54–7.47
3
Fe O @SiO -Pd(OAc) (158 mg, 6 mol%), and Et N (1.2 g, 12 mmol)
(m, 2 H), 7.01–6.94 (m, 2 H).
3
4
2
2
3
were added to this solution. After the addition of HCOOH (368 mg, 8
mmol), the reaction tube was immediately sealed and the reaction
mixture was stirred at 80 °C for 6 h. After cooling to r.t., the Pd cata-
lyst was magnetically separated and the reaction mixture was then
filtered and concentrated under vacuum. The residue was purified by
silica gel column chromatography (light PE/EtOAc 10:1) to give the
desired product 4.
1
3
C NMR (100 MHz, CDCl ):  = 196.6, 161.6, 137.0, 133.7, 120.7,
3
1
19.9, 117.6.
3
-Hydroxybenzaldehyde (2b′)12c
Yield: 107.4 mg (88%); white solid; mp 102–104 °C.
1
H NMR (400 MHz, CDCl ):  = 9.94 (s, 1 H), 7.46–7.40 (m, 3 H), 7.19–
3
7
.15 (m, 1 H), 6.64 (s, 1 H).
o-Phthalaldehyde (4a)12c
1
3
C NMR (100 MHz, CDCl ):  = 192.9, 156.7, 137.7, 130.4, 123.5,
3
Yield: 16.1 mg (12%); white solid; mp 51–53 °C.
122.4, 114.8.
1
H NMR (400 MHz, CDCl ):  = 10.54 (s, 2 H), 8.01–7.96 (m, 2 H), 7.82–
3
4
-Hydroxybenzaldehyde (2c′)12c
7.76 (m, 2 H).
1
3
Yield: 101.4 mg (83%); white solid; mp 115–117 °C.
C NMR (100 MHz, CDCl ):  = 192.4, 136.4, 133.8, 131.1.
3
1
H NMR (400 MHz, CDCl ):  = 9.87 (s, 1 H), 7.82 (d, J = 8.8 Hz, 2 H),
3
m-Phthalaldehyde (4b)12c
6.98 (d, J = 8.4 Hz, 2 H), 6.18 (s, 1 H).
1
3
Yield: 100.5 mg (75%); white solid; mp 88–89 °C.
C NMR (100 MHz, CDCl ):  = 191.2, 161.5, 132.5, 130.0, 116.0.
3
1
H NMR (400 MHz, CDCl ):  = 10.13 (s, 2 H), 8.39 (t, J = 1.8 Hz, 1 H),
3
3
-Formylbenzoic Acid (2d′)12c
8.17 (dd, J = 7.6, 1.6 Hz, 2 H), 7.75 (t, J = 7.6 Hz, 1 H).
1
3
Yield: 121.5 mg (81%); white solid; mp 170–172 °C.
C NMR (100 MHz, CDCl ):  = 191.1, 137.0, 134.6, 131.0, 129.9.
3
1
H NMR (400 MHz, CDCl ):  = 10.12 (s, 1 H), 8.62 (t, J = 1.8 Hz, 1 H),
3
Terephthalaldehyde (4c)12c
8.40–8.37 (m, 1 H), 8.18–8.14 (m, 1 H), 7.69 (t, J = 7.8 Hz, 1 H).
1
3
Yield: 71.5 mg (53%); white solid; mp 113–115 °C.
C NMR (100 MHz, CDCl ):  = 191.2, 170.2, 136.7, 135.7, 133.8,
3
1
1
32.0, 130.4, 129.5.
H NMR (400 MHz, CDCl ):  = 10.15 (s, 2 H), 8.07 (s, 4 H).
3
1
3
C NMR (100 MHz, CDCl ):  = 191.6, 140.0, 130.1.
3
4
-Formylbenzoic Acid (2e′)12c
Yield: 112.6 mg (75%); white solid; mp 244–245 °C.
1
H NMR (400 MHz, DMSO-d ):  = 10.10 (s, 1 H), 8.13 (d, J = 8.4 Hz, 2
Funding Information
6
H), 8.01 (d, J = 8.4 Hz, 2 H).
1
We thank the National Natural Science Foundation of China (No.
3
C NMR (100 MHz, DMSO-d ):  = 193.4, 167.0, 139.3, 136.1, 130.4,
6
2
1462021), the Natural Science Foundation of Jiangxi Province of
1
30.0.
China (No. 20161BAB203086) and Key Laboratory of Functional Small
Organic Molecule, Ministry of Education (No. KLFS-KF-201704) for fi-
Pyridine-3-carbaldehyde (2f′)12c
nancial support.Natio
n
al
N
atural Science Fo
u
n
d
atio
n
o
f
C
h
ina(2
1
4
6
2
0
2
1)Natural
S
cience
F
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u
n
datio
n
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f
Jian
g
x
i
Pro
v
ince (2
0
1
6
1
B
A
B
2
0
3
0
8
6)
Yield: 76.1 mg (71%); colorless oil.
1
H NMR (400 MHz, CDCl ):  = 10.14 (s, 1 H), 9.10 (dd, J = 2.2, 1.0 Hz, 1
3
Supporting Information
H), 8.86 (dd, J = 5.0, 1.8 Hz, 1 H), 8.21–8.18 (m, 1 H), 7.53–7.49 (m, 1
H).
Supporting information for this article is available online at
1
3
C NMR (100 MHz, CDCl ):  = 190.8, 154.7, 152.1, 135.8, 131.4,
3
https://doi.org/10.1055/s-0040-1706621. Su
p
p
orting Inform atio
n
Su
p
p
orting Inform atio
n
124.1.
Thiophene-2-carbaldehyde (2g′)12c
References
Yield: 70.6 mg (63%); colorless oil.
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H NMR (400 MHz, CDCl ):  = 9.94 (s, 1 H), 7.80–7.76 (m, 2 H), 7.23–
3
7.20 (m, 1 H).
1
3
C NMR (100 MHz, CDCl ):  = 183.0, 144.0, 136.4, 135.1, 128.4.
3
©
2021. Thieme. All rights reserved. Synthesis 2021, 53, A–I

I
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