Hafnium(IV) bis(perfluorooctanesulfonyl)imide complex supported on fluorous silica gel catalyzed N-formylation of amines using aqueous formic acid

Article abstract of DOI:10.1016/j.jfluchem.2012.12.010

The treatment of amines with aqueous formic acid in the presence of Hf(NPf₂)₄ supported on fluorous silica gel brings about highly efficient N-formylation to give the corresponding formamides in high yields. The N-formylation reaction not only involves mild conditions, simple operation, and high yields but also recyclable catalyst.

Full text of DOI:10.1016/j.jfluchem.2012.12.010

Journal of Fluorine Chemistry 146 (2013) 11–14
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Short communication
Hafnium(IV) bis(perfluorooctanesulfonyl)imide complex supported on fluorous
silica gel catalyzed N-formylation of amines using aqueous formic acid
*
Mei Hong , Guomin Xiao
School of Chemistry and Chemical Engineering, Southeast University, Nanjing 211189, People’s Republic of China
A R T I C L E I N F O
A B S T R A C T
Article history:
The treatment of amines with aqueous formic acid in the presence of Hf(NPf2)4 supported on fluorous
silica gel brings about highly efficient N-formylation to give the corresponding formamides in high
yields. The N-formylation reaction not only involves mild conditions, simple operation, and high yields
but also recyclable catalyst.
Received 31 October 2012
Received in revised form 17 December 2012
Accepted 22 December 2012
Available online 31 December 2012
ß 2012 Elsevier B.V. All rights reserved.
Keywords:
N-formylation
Amines
Formic acid
Fluorous silica gel
Bis(perfluorooctanesulfonyl)imide
1. Introduction
include sulfated tungstate [29], silica supported perchloric acid
[30]. However, many of these methods suffer from drawbacks such
The formation of amide bonds is of great importance to many
areas of chemistry. The direct condensation reaction carboxylic
acids with amines to form amides is highly desirable due to the
availability of these compounds and the relative cleanliness of such
a process-the only side product being water. It has been reported
that electron-deficient arylboronic acid catalyze dehydrative
condensation of carboxylic with amines through the formation
of monoacyl boronate intermediates [1–10]. Formylation of
amines is an important process in organic and industrial chemical
synthesis with the resulting formamide function being a crossroad
intermediate. Formamides are an extremely useful class of
intermediates in the synthesis of medicinally important hetero-
cycles such as substituted aryl imidazoles [11], 1,2-dihydroqui-
nolines [12], oxazolidinones [13], cancer chemotherapeutic
compounds [14], as reagent for Vilsmeir formylation [15],
allylation [16] hydrosilylation of carbonyl compounds [17] and
for the synthesis of formamidines [18] and isocyanides [19]. In
addition, formyl group also functions as an amino-protecting
group in peptide synthesis [20]. Formic acid has been used as
formylation reagents in combination, with sodium formate [21],
ZnCl2 [22], sulfated titania [23], Amberlite IR 120 [24], indium
metal [25], iodine [26], ZnO [27], sulfonic acid supported
as toxicity, pronged reaction time, formation of undesirable
byproducts and use of non-recoverable catalysts. Hence, we have
been motivated to undertake the challenge to carry out N-
formylation reaction applicable to all types of amines (aliphatic or
aromatic primary and secondary amines) using aqueous formic
acid.
Metal-catalyzed reactions [31] are recognized as attractive and
environmentally benign methods in synthetic chemistry with
regard to the development of green chemistry. Solid acids catalysts
have served as important functional materials in industrial
processes. In particular, for reactions in which water participates
as a reactant or product, only a few solid acids show acceptable
performance. The development of new water-tolerant solid acids is
expected to have a major impact in industrial applications as well
as for scientific aspects. We have overcome this problem by
designing hafnium (IV) bis(perfluorooctanesulfonyl)imide com-
plex (Hf[N(SO2C8F17 2 4
) ] , Hf(NPf2)4) supported on fluorous silica gel
(FSG-Hf(NPf2)4). In the present letter, we report the green,
convenient and efficient synthesis of formamides by the way of
N-formylation of amines, involving the application of catalytic
amount of FSG-Hf(NPf2)4 in aq. 85% formic acid (Scheme 1).
hydroxyapatite encapsulated
g-Fe2O3 [28] and recent additions
2. Results and discussion
The study was initiated by carried out N-formylation of aniline
as our model reaction using various bis(perfluorooctanesulfony-
l)imide complexes immobilized on fluorous silica gel like,
* Corresponding author. Tel.: +86 2552090612; fax: +86 2552090612.
E-mail address: 101100685@seu.edu.cn (M. Hong).
0022-1139/$ – see front matter ß 2012 Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.jfluchem.2012.12.010

12
M. Hong, G. Xiao / Journal of Fluorine Chemistry 146 (2013) 11–14
Table 2
Effect of the amount of formic acid and reaction temperature on N-formylation of
aniline.a
Entry
n (aniline):n (formic acid)
Reaction temperature (8C)
Yield (%)b
1
2
3
4
5
6
1:1
1:2
1:4
1:3
1:3
1:3
70
70
70
70
r.t.
90
Trace
57
Scheme 1. N-formylation of amines with formic acid and FSG-Hf(NPf2)4.
80
86
Trace
80
FSG-HNPf2, FSG-Yb(NPf2)3, FSG-Sc(NPf2)3, FSG-Hf(NPf2)4 (Table 1).
Best yield of formamide was obtained with fluorous silica
supported hafnium (IV) bis(perfluorooctanesulfonyl)imide com-
plex (Table 1, entry 6). In addition, the yields with 0.5 mol% FSG-
Hf(NPf2)4, 1 mol% FSG-Hf(NPf2)4 and 1.5 mol% FSG-Hf(NPf2)4 were
67%, 86% and 78%, respectively, at the time of 1 h. Hence, 1 mol% of
FSG-Hf(NPf2)4 was found to be the optimum catalyst loading.
Having accomplished the optimization of catalyst and catalyst
loading, more experiments were performed to delineate the best
reaction conditions (Table 2). Experiments were performed at
70 8C in different ratio of formic acid to aniline, and the best result
was obtained in 3 equivalent of formic acid (Table 2, entry 4). The
reason would be that some excess formic acid complexed to formic
acid by hydrogen bonding to the carbonyl group [32]. This results
in electronic assistance to nucleophilic attack by the amine
nitrogen atom (Fig. 1). To see the effect of reaction temperature,
reaction was also studied in r.t. and 90 8C (Table 2, entries 5 and 6).
At r.t. no reaction was observed, and at 90 8C we obtained 80% of
the corresponding product. Therefore an amount of 1 mol% FSG-
Hf(NPf2)4, temperature of 70 8C and the reactants in the molar ratio
of 1 (amine):3 (formic acid) were concluded as optimum for
further studies.
a
Reaction conditions: aniline 1 mmol, FSG-Hf(NPf2)4 1 mol%, 1 h.
Isolated yield.
b
the N-formylation of diphenylamine (Table 3, entry 10) which is
secondary hindered amine has been reported to have no reaction
[34] but our protocol show reaction with diphenylamine was
smooth giving 65% yield.
The possibility of recycling the catalyst was examined. For this
reason, the reaction of aniline and formic acid (85%) in the presence
of FSG-Hf(NPf2)4 was studied. When the reaction was completed,
the catalyst was easily recovered from the mixture by filtration. It
was washed with ethyl acetate, and dried at 80 8C under vacuum
for 2 h. The catalyst was reused for N-formylation without any
significant loss of activity up to three cycles (Table 4). This reveals
FSG-Hf(NPf2)4 is reusable for N-formylation reactions.
3. Experimental
3.1. General
Encouraged by the results obtained with the above reaction
conditions, and in order to show the generality and scope of this
new protocol, we used various substituted primary, secondary
amines. All the reactions with substituted amines proceeded very
cleanly and no undesirable side-reactions were observed, although
the yields were highly dependent on the substituents. In all cases
N-formylation reaction was very rapid giving yields ranging from
60% to 88% depending on substrates and the results are
summarized in Table 3. Aromatic primary amines, irrespective
of bearing electron-donating or electron-withdrawing functional-
ities, were found to undergo N-formylation in a facile manner
giving high yields. In contrast, anilines with electron-withdrawing
groups such as chloro, bromo and nitro gave the slightly lower
yield in longer reaction times than anilines with electron-donating
groups such as methyl, methoxy, hydroxy. It is significant that
benzylamine (Table 3, entry 6), that was previously reported to
provide low yield (42%) [33], furnished good yield (80%) following
this reaction protocol. However, the yields were less for open-
chain aliphatic primary amines such as n-butylamine (Table 3,
entry 11) when compared to those for aromatic amines. Previously,
The progress of the reactions was monitored by thin layer
chromatography (TLC). Melting points were obtained with
Shimadzu DSC-50 thermal analyzer and are uncorrected. 1H
NMR and 13C NMR spectra were measured on Bruke Advance
RX500. Fluorous silica gel was purchased from Fluorous Technol-
ogies Inc. All chemicals (AR grade) were commercially available
and used without further purification.
3.2. Preparation of catalyst
Hf(NPf2)4 used in this study was synthesized according to a
method described in literature [35]. The synthesis of FSG-Hf(NPf2)4
was carried out as reported in literature [36]. Into a solution of
hafnium (IV) bis(perfluorooctanesulfonyl)imide complex (200 mg)
in ethanol (10 mL), fluorous silica gel (2 g) was added and the
resulting mixture was stirred for 1 h at room temperature. After
removal of the solvent under reduced pressure, residual FSG-
supported hafnium (IV) bis(perfluorooctanesulfonyl)imide com-
plex was dried under vacuum at 80 8C for 6 h.
Table 1
Effect of different catalysts and catalyst loading on N-formylation of aniline.a
Entry
Catalyst
Catalyst
Yield (%)b
loading (mol%)
1
2
3
4
5
6
7
8
FSG-HNPf2
1
Trace
31
FSG-HNPf2
4
FSG-Yb(NPf2)3
FSG-Sc(NPf2)3
FSG-Sn(NPf2)4
FSG-Hf(NPf2)4
FSG-Hf(NPf2)4
FSG-Hf(NPf2)4
1
60
1
63
1
71
1
86
0.5
1.5
67
78
a
Reaction conditions: aniline 1 mmol, formic acid 3 mmol, 70 8C, 1 h.
Isolated yield.
b
Fig. 1. Electrophic assistance to nucleophilic attack.

M. Hong, G. Xiao / Journal of Fluorine Chemistry 146 (2013) 11–14
13
Table 3
1H), 9.22 (brs, 1H), 8.46 (d, J = 11.2, 1H), 6.50–7.38 (m, 4H);
13C NMR (125 MHz, CDCl3)
115.1, 120.1, 153.4, 158.7, 162.5.
(6) N-Benzylformamide: m.p. 60–62 8C, literature [28] 60–62 8C;
1H NMR (500 MHz, DMSO-d6)
8.29 (s, 1H), 7.24–7.47 (m,
5H), 5.75 (s, 1H), 4.51 (d, J = 6.0 Hz, 2H); 13C NMR (125 MHz,
CDCl3) 41.5, 126.8, 129.1, 130.6, 134.1, 162.3.
(7) N-(4-Nitrophenyl)formamide: m.p. 193–195 8C, literature
[28] 194–195 8C; 1H NMR (500 MHz, DMSO-d6)
10.80 (s,
N-Formylation of amines using FSG-Hf(NPf2)4.a
d
Entry
R
R0
Time (h)
Yield (%)b
d
1
2
Ph
H
H
H
H
H
H
H
H
H
Ph
H
1
86
88
84
87
85
80
80
82
81
65
60
4-CH3C6H4
2-CH3C6H4
4-OCH3C6H4
4-OH C6H4
Ph-CH2
1.5
1.5
1.5
1.5
2
3
d
4
5
d
6
1H), 8.39 (s, 1H), 8.20 (d, J = 8.0 Hz, 2H), 7.81 (d, J = 8.0 Hz,
7
4-NO2C6H4
4-ClC6H4
4-BrC6H4
Ph
3
2H); 13C NMR (125 MHz, CDCl3)
143.2, 144.4, 160.0.
d 116.8, 119.4, 124.9, 125.6,
8
3
9
3
10
11
4
(8) N-(4-Chlorophenyl)formamide: m.p. 99–101 8C, literature
CH3(CH2)3
2
[39] 99–101 8C; 1H NMR (500 MHz, CDCl3)
d 8.67 (d, 1H),
a
8.38 (s, 1H), 7.02–7.52 (m, 4H); 13C NMR (125 MHz, CDCl3)
120.5, 121.7, 129.5, 130.3, 159.7, 163.1.
d
Reaction conditions: amines 1 mmol, formic acid 3 mmol, FSG-Hf(NPf2)4
1 mol%, 70 8C.
b
Isolated yield.
(9) N-(4-Bromophenyl) formamide: m.p. 115–119 8C, literature
[37] 116–117 8C; 1H NMR (500 MHz, CDCl3)
9.21 (brs, 1H),
d
3.3. General procedure for N-formylation of amines
8.46 (d, J = 11.32, 1H), 7.39–7.45 (m, 2H), 6.93–6.99 (m, 2H);
13C NMR (125 MHz, CDCl3)
121.1, 132.7, 158.4, 163.3.
d 115.4, 115.8, 116.3, 116.6, 120.9,
To a mixture of HCO2H (3 mmol) and FSG-Hf(NPf2)4 (1 mol%)
was added an amine (1 mmol), and then the reaction mixture was
heated in an oil bath at 70 8C and stirred with a magnetic stirrer.
The progress of the reaction was monitored by TLC. After the
reaction was complete, ethyl acetate was added to the reaction
mixture, and FSG-Hf(NPf2)4 was removed by filtration. The filtrate
was extracted with ethyl acetate. The combined organic layer was
then washed with saturated solution of NaHCO3, brine and dried
over anhydrous Na2SO4. After remove of the solvent, the crude
product was obtained. This was further purified by recrystalliza-
tion with diethyl ether to obtain the pure product. The structure of
the products was confirmed by 1H NMR and 13C NMR.
(10) N,N-Diphenylformamide: m.p. 67–71 8C, literature [28] 67–
71 8C; 1H NMR (500 MHz, CDCl3)
8.68 (s, 1H), 7.39–7.43 (m,
4H), 7.27–7.34 (m, 4H), 7.18 (d, J = 7.4 Hz, 2H); 13C NMR
(125 MHz, CDCl3) 125.4–130.2, 140.0, 162.3.
(11) N-Butylformamide: 1H NMR (500 MHz, CDCl3)
d
d
d
8.56 (s, 1H),
5.79 (brs, 1H), 3.21–3.34 (m, 2H), 1.25–1.60 (m, 4H), 0.95 (t,
J = 7.10, 3H); 13C NMR (125 MHz, CDCl3)
d 13.5, 19.3, 31.5,
37.1, 161.2.
4. Conclusion
(1) N-Phenylformamide: m.p. 46–48 8C, literature [28] 46–47 8C;
In conclusion, we have developed a simple, environmental and
efficient FSG-Hf(NPf2)4 catalyzed method for the N-formylation of
primary and secondary amines. This protocol can be used to
generate a diverse range of primary and secondary formamides in
good yields. The catalyst is completely recoverable and the
efficiency of the catalyst remains unaltered even after three cycles.
1H NMR (500 MHz, DMSO-d6)
d
8.71 (d, J = 11.0 Hz, 1H), 8.45
(d, J = 11.0 Hz, 1H), 7.10–7.59 (m, 5H); 13C NMR (125 MHz,
CDCl3) 119.2, 120.7, 125.3, 125.7, 129.5, 130.2, 137.4, 137.6,
d
160.5, 163.8.
(2) N-(4-Methylphenyl)formamide: m.p. 51–55 8C, literature [28]
50–54 8C; 1H NMR (500 MHz, DMSO-d6)
d 8.60 (d, J = 8.0 Hz,
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