Formylation of alcohol with formic acid under solvent-free and neutral conditions catalyzed by free I2 or I2 generated in situ from Fe(NO3)3·9H2O/NaI

Article abstract of DOI:10.1016/S1872-2067(10)60160-X

Different alcohols were formylated by formic acid under solvent-free conditions in the presence of iodine as the catalyst with good-to-high yields at room temperature. I₂ generated in situ from Fe(NO₃) ₃·9H₂O/NaI also catalyzed the formylation of the alcohols under solvent-free conditions. This gives a green and efficient reaction at room temperature, in which the use of toxic and corrosive molecular I₂ is avoided.

Full text of DOI:10.1016/S1872-2067(10)60160-X

CHINESE JOURNAL OF CATALYSIS
Volume 32, Issue 1, 2011
Online English edition of the Chinese language journal
RESEARCH PAPER
Cite this article as: Chin. J. Catal., 2011, 32: 60–64.
Formylation of Alcohol with Formic Acid under Solvent-Free
and Neutral Conditions Catalyzed by Free I2 or I2 Generated
in Situ from Fe(NO3)3·9H2O/NaI
Rostami AMIN1,*, Khazaei ARDESHIR2,#, Alavi-Nik HEIDAR ALI2, Toodeh-Roosta ZAHRA2
1Department of Chemistry, Faculty of Science, University of Kurdistan, Zip Cod 66177-15175, Sanandaj, Iran
2Faculty of Chemistry, Bu-Ali Sina University, Zip Cod 65178-38683, Hamadan, Iran
Abstract: Different alcohols were formylated by formic acid under solvent-free conditions in the presence of iodine as the catalyst with
good-to-high yields at room temperature. I2 generated in situ from Fe(NO3)3·9H2O/NaI also catalyzed the formylation of the alcohols under
solvent-free conditions. This gives a green and efficient reaction at room temperature, in which the use of toxic and corrosive molecular I2 is
avoided.
Key words: alcohol; formic acid; formylation; iodine; in situ iodine; solvent-free
Formylation is an important reaction in organic chemistry
because it can affect selectivity by putting acetate or other ester
protecting groups on a substrate [1]. Furthermore, if the alco-
holic group is to be oxidized later in the synthetic scheme, the
formylated alcoholic does not need to be de-protected, in which
case direct oxidation under Oppenauer conditions can be used
[2]. In addition, formate esters are useful synthetic reagents and
intermediates [3–5]. Despite these potential uses, the formyl
protecting group has been rather overlooked. This is partly due
to the fact that efficient formylation procedures under mild
conditions are not available because the unstable formyl halide
or anhydride is unsuitable for use in formylation.
1.1 General procedure for the formylation of alcohol or
thiol by formic acid under solvent-free conditions catalyzed
by I2
To a stirred mixture of I2 (0.1 mmol) and formic acid (20
mmol), alcohol or thiol (1 mmol) was added, and stirring was
continued at room temperature for an appropriate time. After
completion of the reaction (monitored by TLC), iodine and
formic acid were destroyed by adding saturated sodium thi-
osulfate solution (5 ml) and 10% aqueous solution of NaOH (5
ml), respectively. Diethyl ether (10 ml × 2) was added and the
phases were separated. The organic phase was washed with
brine (5 ml × 2) and dried (Na2SO4). Evaporation of the solvent
under reduced pressure to give the almost pure product. In
some cases, flash column chromatography with silica gel
(n-hexane/EtOAc 10:1) was used to provide the pure product.
All the products were characterized by IR, 1H NMR, MS, and
elemental analysis.
Several formylation procedures have been reported, but
these were based on formylation with formic acid in the pres-
ence of a dehydrating agent [6–8], transesterification with
ethyl/methyl formate [9–13], with active formates [14–16] or
with N-formyl compounds [17,18], that is, most of these
methods use uncommon, moisture sensitive, thermally unsta-
ble, and expensive reagents or catalysts. This work reports a
procedure that does not have these disadvantages.
1.2 General procedure for formylation of alcohol by
formic acid catalyzed with I2 generated in situ from
Fe(NO3)3·9H2O/NaI
1 Experimental
Received 13 June 2010. Accepted 4 September 2010.
*Corresponding author. Tel: +98-918-3730910; Fax: +98-871-6624133; E-mail: a_rostami372@yahoo.com
# Corresponding author. Tel: +98-918-3139025; Fax: +98-811-8272404; E-mail: khazaei_1326@yahoo.com
Foundation item: Supported by Bu-Ali Sina University and University of Kurdistan Research Councils.
Copyright © 2011, Dalian Institute of Chemical Physics, Chinese Academy of Sciences. Published by Elsevier BV. All rights reserved.
DOI: 10.1016/S1872-2067(10)60160-X

AMIN Rostami et al. / Chinese Journal of Catalysis, 2011, 32: 60–64
Alcohol (1 mmol) was added to a mixture of Fe(NO3)3·9H2O
71.45; H, 10.72. MS (m/z): 180 [M+].
(0.1 mmol), NaI (0.2 mmol), and HCOOH (20 mmol). The
mixture was stirred vigorously at room temperature for a spe-
cific time. After completion of the reaction, the sample was
treated as described in section 1.1.
2-Adamantanyl formate (11). IR (KBr, cmꢀ1): v 2940, 2864,
1
1725, 1471, 1183. H NMR (90 MHz, CDCl3): į 0.82–1.45
(complex, 14H), 4.93 (m, 1H), 7.97(s, 1H). Anal. Calcd. for
C11H16O2: C, 73.30; H, 8.95; O, 17.756. Found: C, 73.12; H,
9.0. MS (m/z): 180 [M+].
1.3 Spectral data of some known formates
2-Heptanyl formate (12). IR (Neat, cmꢀ1): v 2959, 2872,
1731, 1456, 1378. 1H NMR (90 MHz, CDCl3): į 0.80–1.12 (m,
14H), 4.91 (m, 1H), 7.95 (s, 1H). Anal. Calcd. for C8H16O2: C,
66.63; H, 11.18; O, 22.19. Found: C, 66.80; H, 11.28. MS
(m/z): 144 [M+].
4-Chlorobenzyl formate (1). IR (Nujol, cmꢀ1): v 3037, 2933,
1
1725, 1450. H NMR (90 MHz, CDCl3): į 5.12 (s, 2H), 7.30
(m, 4H), 8.15 (s, 1H). Anal. Calcd. for C8H7ClO2: C, 56.32; H,
4.14; Cl, 20.78; O, 18.76. Found: C, 56.57; H, 4.10. MS (m/z):
170 [M+].
1-Adamantanyl formate (14). IR (KBr, cmꢀ1): v 2940, 2985,
1
1750, 1485, 1135. H NMR (90 MHz, CDCl3): į 1.61–2.05
4-Nitrobenzyl formate (3). IR (KBr, cmꢀ1): v 3082, 2854,
1726, 1607, 1521, 1459, 1347, 1152, 846, 738. 1H NMR
(90MHz, CDCl3): į 5.27 (s, 2H), 7.46–7.54 (m, 2H), 8.15–8.24
(m, 3H). Anal. Calcd. for C8H7NO4: C, 53.04; H, 3.89; N, 7.73;
O, 35.33. Found: C, 53.21; H, 3.50; N, 7.48. MS (m/z): 181
[M+].
Cinnamyl formate (4). IR (Neat, cmꢀ1): v 3027, 2934, 2975,
1724, 1449, 1494, 1165. 1H NMR (90 MHz, CDCl3): į 4.82 (d,
2H), 6.23–6.68 (m, 2H), 7.25–7.40 (m, 5H), 8.12 (s, 1H). Anal.
Calcd. for C10H10O2: C, 74.06; H, 6.21; O, 19.73. Found: C,
73.96; H, 6.15. MS (m/z): 162 [M+].
(complex, 15H), 7.99 (s, 1H). Anal. Calcd. for C11H16O2: C,
73.30; H, 8.95; O, 17.756. Found: C, 73.62; H, 8.69. MS (m/z):
180 [M+].
1,4-Cyclohexanediyl diformate (16). IR (Nujol, cmꢀ1): v
1
2983, 2969, 1727, 1473, 1150. H NMR (90 MHz, CDCl3): į
1.52 (m, 4H), 1.80 (m, 4H), 4.85 (m, 2H), 8.04 (s, 2H). Anal.
Calcd. for C8H12O4: C, 55.81; H, 7.02; O, 37.17. Found: C,
55.85; H, 7.20. MS (m/z): 172 [M+].
2 Results and discussion
2-Phenylethyl formate (5). IR (Neat, cmꢀ1): v 3023, 2980,
2975, 1760, 1155. 1H NMR (90 MHz, CDCl3): į 2.9 (m, 2H),
4.40 (t, 2H), 7.3 (m, 5H), 8.01 (s, 1H). Anal. Calcd. for
C9H10O2: C, 71.98; H, 6.71; O, 21.31. Found: C, 72.07; H, 6.50.
MS (m/z): 150 [M+].
In recent years, molecular iodine has received considerable
attention as an inexpensive and readily available catalyst for
various organic transformations under very mild and conven-
ient conditions because it gives the corresponding products in
excellent yields with high selectivity. This is due to the oxi-
dizing ability and Lewis acidity of iodine [19]. As part of our
work on the catalytic application of reagents in the transfor-
mation of organic functional groups [20–24], we report here
the formylation of a wide range of alcohols using formic acid at
room temperature under solvent-free conditions in the presence
of a catalytic amount of molecular iodine.
Diphenylmethyl formate (6). IR (Neat, cmꢀ1): v 3032, 2930,
1
2854, 1731, 1495, 1456, 1157. H NMR (90 MHz, CDCl3): į
7.13 (s, 1H), 7.25–7.42 (m, 10H), 8.26 (s, 1H). Anal. Calcd. for
C14H12O2: C, 79.22; H, 5.70; O, 15.08. Found: C, 79.42; H,
5.80. MS (m/z): 212 [M+].
1-Phenylethyl formate (7). IR (Neat, cmꢀ1): v 3020, 2988,
2978, 1757, 1165. 1H NMR (90 MHz, CDCl3): į 1.53 (d, 3H),
5.97 (q, 1H), 7.34 (m, 5H), 8.06 (s, 1H). Anal. Calcd. for
C9H10O2: C, 71.98; H, 6.71; O, 21.31. Found: C, 71.75; H, 6.92.
MS (m/z): 150 [M+].
Cyclohexyl formate (8). IR (Nujol, cmꢀ1): v 2980, 2970,
1725, 1475, 1150. 1H NMR (90 MHz, CDCl3): į 0.95 (m, 4H),
1.22 (m, 4H), 1.67 (m, 2H), 4.82 (m, 1H), 8.02 (s, 1H). Anal.
Calcd. for C7H12O2: C, 65.60; H, 9.44; O, 24.97. Found: C,
65.35; H, 9.27. MS (m/z): 128 [M+].
We first optimized the reaction conditions by evaluating the
influence of different amounts of formic acid and catalyst on
the time and product yield in the formylation of benzhydrole,
which was used as a model. The results are shown in Table 1.
The optimum amount was 20 mmol of HCOOH in the pres-
ence of 0.1 mmol of I2, which gave the complete conversion
of benzhydrole to the corresponding formate ester.
Table 1 Optimization of amount of formic acid and iodine for the for-
Cyclododecanyl formate (9). IR (Neat, cmꢀ1): v 2940, 2864,
1725, 1471, 1183. 1H NMR (90 MHz, CDCl3): į 1.32–1.53 (m,
22H), 5.11 (b, 1H), 8.01 (s, 1H). Anal. Calcd. for C13H24O2: C,
73.54; H, 11.39; O, 15.07. Found: C, 73.75; H, 11.19. MS
(m/z): 212 [M+].
Methyl formate (10). IR (Neat, cmꢀ1): v 3058, 2959, 2872,
1723, 1456, 1191. 1H NMR (90 MHz, CDCl3): į 0.85–1.15 (m,
15H), 1.45–2.0 (m, 3H), 4.74 (m, 1H), 7.99 (s, 1H). Anal.
Calcd. for C11H20O2: C, 71.70; H, 10.94; O, 17.36. Found: C,
mylation of benzhydrole (1 mmol) at room temperature
HCOOH (mmol)
I2 (mmol)
0.1
Time (min)
Conversiona (%)
1
5
30
30
30
3
25
45
0.1
10
20
20
20
0.1
60
0.1
100
90
0.02
0.05
30
30
100
aDetermined by 1H NMR.

AMIN Rostami et al. / Chinese Journal of Catalysis, 2011, 32: 60–64
In order to determine the scope of the reaction, a series of
2, entry 18). Due to the nearly neutral nature of the reaction
medium, no elimination byproduct was observed.
structurally diverse alcohols including primary (benzylic, al-
lylic, and acyclic), secondary (benzylic, cyclic, and acyclic),
and tertiary (sterically hindered and acid-sensitive) alcohols
were used. The formylation results under the optimized reac-
tion conditions are shown in Table 2. The different alcohols
were successfully converted to the corresponding formate
esters in short reaction time in almost quantitative yields. This
method was also useful for the formylation of diol (Table 2,
entry 16). Thiols were converted to the corresponding formate
thioester in low yields (Table 2, entries 19 and 20). We ob-
served that 1-naphtol, as a model for phenols, was not con-
verted in this reaction even after prolonged reaction time (Table
Although molecular iodine is a versatile reagent in organic
synthesis, it is corrosive, which makes its use unattractive. Very
recently, we reported a convenient system to generate I2 in situ
from Fe(NO3)3·9H2O/NaI, and measured the amount of I2
generated in situ by UV/Vis spectrophotometry [22,23]. Sub-
sequently, we discovered that I2 generated in situ from
Fe(NO3)3·9H2O/NaI was an effective reagent for the formyla-
tion of a wide range of alcohols by HCOOH, giving good
yields under solvent-free conditions at room temperature (Ta-
ble 3). Compounds that were formylated in this way were
primary and secondary (hindered and unhindered) alcohols and
Table 2 Formylation of different alcohols by formic acid (20 mmol) in the presence of a catalytic amount of I2 (0.1 mmol) under solvent-free conditions
at room temperature
ROH
ROCHO
R = Benzylic, Linear, Cyclic
Entry
Substrate
Producta
Time (min)
Isolated yield (%)
1
2
3
4
5
6
7
4-Cl-C6H4CH2OH
4-OMe-C6H4CH2OH
4-NO2-C6H4CH2OH
C6H4CH2=CH2CH2OH
PhCH2CH2OH
4-Cl-C6H4CH2OCHO
4-OMe-C6H4CH2OCHO
4-NO2-C6H4CH2OCHO
35
7
96
94
88
70
93
94
93
60
45
10
3
C6H4CH2=CH2CH2OCHO
PhCH2CH2OCHO
PhCH(OH)Ph
PhCH(OCHO)Ph
CH3CH(Ph)OH
CH3CH(Ph)OCHO
40
OH
OCHO
8
40
90
9
60
96
OH
OH
OCHO
OCHO
10
60
91
OH
OCHO
11
12
13
30
40
90
97
91
76
CH3(CH2)4CH(OH)CH3
OH
CH3(CH2)4CH(OCHO)CH3
OCHO
CH
CH3
2 C
CH3
CH
CH3
2 C
CH3
14
120
77
OH
OCHO
CH3
CH3
CH
HO
C
C
CH2CH3
CH
C
C
CH2CH3
15
16
140
35
80
89
OH
OCHO
OH
OH
OHCO
OCHO
OCHO
17
120
—
18
19
PhSH
PhCH2SH
PhSCHO
PHCH2SCHO
120
240
60
45
aProducts were characterized by comparison of their spectral data (IR, 1H NMR, MS, and elemental analysis) with those of standard samples [9–14].

AMIN Rostami et al. / Chinese Journal of Catalysis, 2011, 32: 60–64
Table 3 Formylation of different alcohols (1 mmol) in the presence of Fe(NO3)3·9H2O (0.1 mmol)/NaI (0.2 mmol) and formic acid (20 mmol) under
solvent-free conditions at room temperature
Entry
Substrate
Producta
Time (min)
Isolated yield (%)
1
2
3
4
5
6
7
8
4-Cl-C6H4CH2OH
4-OMe-C6H4CH2OH
4-NO2-C6H4CH2OH
C6H4CH2=CH2CH2OH
PhCH2CH2OH
4-Cl-C6H4CH2OCHO
4-OMe-C6H4CH2OCHO
4-NO2-C6H4CH2OCHO
C6H4CH2=CH2CH2OCHO
PhCH2CH2OCHO
45
13
95
94
69
76
97
90
87
120
90
60
PhCH(OH)Ph
PhCH(OCHO)Ph
35
CH3CH(Ph)OH
CH3CH(Ph)OCHO
45
OH
OCHO
60
90
9
240
90
OH
OH
OCHO
OCHO
10
11
150
82
OH
OCHO
90
150
120
92
94
50
12
13
CH3(CH2)4CH(OH)CH3
CH3
CH3(CH2)4CH(OCHO)CH3
CH3
CH
C
C
CH2CH3
CH
C
C
CH2CH3
OCHO
OH
14
15
16
140
45
OH
OH
OCHO
OCHO
CH C CH
CH
CH3
2 C
CH3
2
3
240
50
—
92
CH
3
HO
OH
OHCO
OCHO
aProducts were characterized by comparison of their spectral data (IR, 1H NMR, MS, and CHN) with those of authentic samples [9–14].
ꢀ
ꢀ
į+
I
į
I
į
O
H
H
H
ROH
į+
HO
I2
+ I2
H2O
+
O
O
+
RO
HO
Scheme 1. Proposed iodine-promoted formylation.
diols. Tertiary alcohols were converted to the corresponding
formate esters in low yields (Table 3, entries 14–16). We ob-
served that phenols and thiols were not converted in this reac-
tion even after prolonged reaction time.
would be a green procedure.
References
1
2
3
Greene T W, Wuts P G M. Protective Groups in Organic Synthe-
sis. 3nd Ed. New York: Wiley, 1999
On the basis of the accepted mechanism for iodine as the
catalyst in various organic transformations [19], it is proposed
that in this reaction the carbonyl of formic acid is activated by
iodine, which makes the carbonyl group susceptible to nu-
cleophilic attack. The mechanism proposed for the reaction is
shown in Scheme 1.
Rignold H J, Loeken B, Roseknranz G, Sondheimer F. J Am
Chem Soc, 1956, 78: 816
Mandai T, Matsumoto T, Kawada M, Tsuji J. J Org Chem, 1992,
57: 1326
4
5
6
Garner C M, Prince M E. Tetrahedron Lett, 1994, 35: 2463
Ali B E, Alper H. J Mol Catal A, 1995, 96: 197
Strazzolini P, Giumanian A G, Causi S. Tetrahedron, 1990, 46:
1081
3 Conclusions
Iodine shows good catalytic activity for the formylation of a
variety of alcohols by formic acid, and gives good to excellent
yields under solvent-free conditions at room temperature. I2
generated in situ from Fe(NO3)3·9H2O/NaI was also shown to
be an effective catalyst for the formylation of alcohol, which
7
8
Olah G A, Vankar Y D, Arvanaghi M, Sommer M J. Angew
Chem, Int Ed, 1979, 18: 614
Kitagawa T, Arita J, Nagahata A. Chem Pharm Bull, 1994, 42:
1655

AMIN Rostami et al. / Chinese Journal of Catalysis, 2011, 32: 60–64
9
Habibi M H, Tangestaninejad S, Mirkhani V, Yadollahi B. Tetra-
hedron, 2001, 57: 8333
18 Kashima J C, Arao H, Hibi S, Omote Y. Tetrahedron Lett, 1989,
30: 1561
10 Zolfigol M A, Chehardoli G, Dehghanian M, Niknam K, Shirini
F, Khoramabadi-Zad A. J Chin Chem Soc, 2008, 55: 885
11 Ghorbani-Vaghei R,Veisi H, Amiri M. J Iran Chem Soc, 2009, 6:
761
19 Togo H, Iida S. Synlett, 2006: 2159
20 Khazaei A, Rostami A, Mahboubifar M. Catal Commun, 2007, 8:
383
21 Khazaei A, Rostami A, Raiatzadeh A, Mahboubifar M. Can J
12 Niknam K, Zolfigol M A, Saberi D, Khonbzi M. Chin J Chem,
2009, 27: 1548
Chem, 2007, 85: 336
22 Rostami A, Rahmati S, Khazaei A. Monatsh Chem, 2009, 140:
13 Niknam K, Saberi D. Appl Catal A, 2009, 366: 220
14 Ram R N, Meher N K. Tetrahedron, 2002, 58: 2997
15 Deutsch J, Niclas H J. Synth Commun, 1993, 23: 1561
16 Kabouche A, Kabouche Z. Tetrahedron Lett, 1999, 40: 2127
17 Chu F, Dueno E E, Jung K W. Tetrahedron Lett, 1999, 40: 1847
663
23 Khazaei A, Rahmati S, Rostami A. Helv Chim Acta, 2009, 92:
1434
24 Rostami A, Ahmad-Jangi F, Zarehbin M R, Akradi J. Synth
Commun, 2010, 40: 1500