Solvent-free chemoselective synthesis of 1,1-diacetates catalyzed by Cu(NO3)2·3H2O

Article abstract of DOI:10.1080/00397910701198906

1,1-Diacetates have been synthesized by the reaction of a variety of aldehydes with acetic anhydride in the presence of cupric nitrate as catalyst under solvent-free conditions. Ketones were not converted to the corresponding diacetates under these conditions. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397910701198906

Synthetic Communicationsw, 37: 1121–1126, 2007
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910701198906
Solvent-Free Chemoselective Synthesis
of 1,1-Diacetates Catalyzed
.
by Cu(NO3)2 3H2O
Majid M. Heravi, Khadijeh Bakhtiari, Maryam H. Tehrani,
and Hossein A. Oskooie
Department of Chemistry, School of Sciences, Azzahra University,
Vanak, Tehran, Iran
Abstract: 1,1-Diacetates have been synthesized by the reaction of a variety of
aldehydes with acetic anhydride in the presence of cupric nitrate as catalyst under
solvent-free conditions. Ketones were not converted to the corresponding diacetates
under these conditions.
.
Keywords: acylals, aldehydes, chemoselective, Cu(NO3)2 3H2O, 1,1-diacetates
The toxic and volatile nature of many organic solvents that are widely used in
organic synthesis, particularly chlorinated hydrocarbons, have posed a serious
threat to the environment. To address some of these issues, attempts have been
made to develop solvent-free processes, which to some extent have succeeded
in achieving some chemical transformations.[1–3]
There are many groups available for protection of aldehydes in organic
synthesis.[4] Acylals or 1,1-diacetates and acetals are synthetically useful pro-
tecting groups for aldehydes. These compounds are stable towards aqueous
acids and mild bases.[5–7] Furthermore, chemoselective preparation of the
1,1-diacetates in the presence of ketones have been reported.[5–7] Acylals
can be converted into other useful functional groups by reaction with
Received in Poland June 6, 2006
Address correspondence to Majid M. Heravi, Department of Chemistry, School of
Sciences, Azzahra University, Vanak, Tehran, Iran. E-mail: mmh1331@yahoo.com
1121

1122
M. M. Heravi et al.
Scheme 1.
appropriate nucleophiles[8] and used as carbonyl surrogates for asymmetric
synthesis.[9] These compounds have also been applied as cross-linking
reagents for cellulose in cotton.[10]
Recently, a number of methods have been developed for conversion of
aldehydes to the corresponding 1,1-diacetates. They can be prepared from
aldehydes and acetic anhydride in the presence of strong protic acids, Lewis
acids, or several inorganic heterogeneous catalysts.[11–16] However, some of
those methods suffer from some drawbacks such as low yields, long
reaction times, corrosion, effluent pollution, and unrecoverable catalysts.
Therefore, there is still a demand for the development of efficient and envir-
onmentally benign catalytic methods for this reaction using inexpensive and
nonpolluting reagents.
In continuation of our interest in synthesis of 1,1-diacetates,[17–20] we
now report an efficient and green procedure for the conversion of aldehydes
into 1,1-diacetates catalyzed by cupric nitrate (Scheme 1).
The reaction of various aldehydes with Ac2O in the presence of
.
Cu(NO3)2 3H2O afforded 1,1-diacetates in high yields (Table 1). In all
cases, the reactions proceeded efficiently at 808C under solvent-free con-
ditions and completed within 1–2 h. All of the products were characterized
by comparison of their spectra and physical data with those reported in the lit-
erature. Both aliphatic and aromatic aldehydes worked well under similar
reaction conditions. This method is effective for the preparation of acylals
from both aromatic aldehydes bearing electron-donating or electron-with-
drawing groups.
To show the chemoselectivity of the method for the protection of various
carbonyl groups, we investigated competitive reactions for the preparation of
acylal from benzaldehyde in the presence of benzophenone using a catalytic
.
amount of Cu(NO3)2 3H2O under solvent-free conditions at 808C. We
found that benzaldehyde was converted to the corresponding 1,1-diacetate
in high selectivity in the presence of acetophenone. This suggested that che-
moselective protection of aldehydes in the presence of ketones could be
achieved with this procedure (Scheme 2).
The nature of the substituents on the aromatic ring has a substantial effect
on the competitive reaction, as demonstrated in Scheme 3.
The catalyst was easily separated by simple filtration. Thus, this
procedure provides easy access to the preparation of various acylals with a
wide range of substitution patterns. This method offers several advantages

Chemoselective Synthesis of 1,1-Diacetates
Table 1. Synthesis of 1,1-diacetates using Cu(NO3)2 3H2O
1123
.
Mp (8C)
Reported
Entry
Substrate
Time
Yield (%)a
Found
b
1
2
Isobutyraldehyde
Butyraldehyde
Benzaldehyde
60 min
75 min
60 min
60 min
75
73
—
—
—
—
b
3
99
93
42–43
80
44–45[21]
81–82[22]
70–71[23]
64–65[24]
81–82[25]
90[26]
4
4-Methyl-benzaldehyde
5
2-Methoxy-benzaldehyde 85 min
4-Methoxy-benzaldehyde 60 min
86
95
68–70
64–65
80
6
7
4-Chloro-benzaldehyde
2-Nitro-benzaldehyde
3-Nitro-benzaldehyde
4-Nitro-benzaldehyde
Cinnamaldehyde
70 min
120 min
120 min
85 min
100 min
24 h
92
86
8
88–89
65–66
124–126 125–126[24]
9
99
92
64–66[24]
10
11
12
13
88
No reaction
No reaction
86
—
—
84–86[26]
Acetophenone
Benzophenone
—
—
24 h
aYields analyzed by GC.
bThe oily products were obtained.
such as high conversion, relatively short reaction times, cleaner reaction
profiles, high chemoselectivity in the presence of ketones, solvent-free
conditions, simple experiment and workup procedures, and application of
an inexpensive and nontoxic catalyst.
In summary, we describe an efficient protocol for the synthesis of 1,1-
.
diacetates from a variety of aldehydes and Ac2O using Cu(NO3)2 3H2O as
catalyst in solvent-free conditions. This method is very useful to prepare a wide
variety of acylals in the presence of ketones under extremely mild conditions.
EXPERIMENTAL
Melting points were measured using the capillary-tube method with an elec-
trothermal 9200 apparatus. 1H NMR spectra were recorded on a Bruker
AQS Avance 300-MHz spectrometer using TMS as an internal standard
(CDCl3 solution). IR spectra were recorded from KBr disk on the FT-IR
Scheme 2.

1124
M. M. Heravi et al.
Scheme 3.
Bruker Tensor 27. All products are known compounds and were identified by
comparison of their spectra and physical data with those of references.[21–26]
Preparation of Acylals: General Procedure
Cupric nitrate (10 mol%) was treated with aldehyde (1 mmol) and acetic
anhydride (3 mmol). The slurry mixture was stirred for the indicate time
(Table 1) at 808C. The progress of the reaction was monitored by thin-layer
chromatography (TLC). After completion of the reaction, the catalyst was
filtered and washed with Et2O (5 mL). Then the filtrate was washed with 5%
NaHCO3 (5 mL) and brine (2 Â 5 mL) successively and dried (MgSO4). The
solvent was evaporated under reduced pressure. The crude product was
purified over silica gel by column chromatography to provide the pure product.
REFERENCES
1. Toda, F.; Tanaka, K. Solvent-free organic synthesis. Chem. Rev. 2000, 100, 1025.
2. Dolman, S. J.; Satterly, E. S.; Hoveyda, A. H.; Schrock, R. R. Efficient catalytic
enantioselective synthesis of unsaturated amines: Preparation of small- and
medium-ring cyclic amines through Mo-catalyzed asymmetric ring-closing
metathesis in the absence of solvent. J. Am. Chem. Soc. 2002, 124, 6991.
3. Balema, V. P.; Wiench, J. W.; Pruski, M.; Pecharsky, V. K. Mechanically induced
solid-state generation of phosphorus ylides and the solvent-free Wittig reaction.
J. Am. Chem. Soc. 2002, 124, 6244.
4. Green, T. W.; Wuts, P. G. M. Protecting Groups in Organic Chemistry, 3rd ed.;
Wiley and Sons: New York, 1999.
5. Chakaraborti, A. K.; Thilagavathi, R.; Kumar, R. Copper (II) tetrafluoroborate–
catalyzed formation of aldehyde-1,1-diacetates. Synthesis. 2004, 831.
6. Romanelli, G. P.; Thomas, H. J.; Baronetti, G. T.; Autino, J. C. Solvent-free
catalytic preparation of 1,1-diacetates from aldehydes using a Wells–Dawson
.
acid (H6P2W18O62 24H2O). Tetrahedron Lett. 2003, 44, 1301.

Chemoselective Synthesis of 1,1-Diacetates
1125
7. Karimi, B.; Maleki, J. Lithium trifluoromethanesulfonate (LiOTf) as a recyclable
catalyst for highly efficient acetylation of alcohols and diacetylation of aldehydes
under mild and neutral reaction conditions. J. Org. Chem. 2003, 68, 4951.
8. Heerden, F. R.; Huyser, J. J.; Williams, D. B. G.; Holzapfel, C. W. Palladium-
catalysed substitution reactions of geminal allylic diacetates. Tetrahedron Lett.
1998, 39, 5281.
9. Trost, B. M.; Lee, C. Gem-Diacetates as carbonyl surrogates for asymmetric
synthesis: Total syntheses of sphingofungins E and F. J. Am. Chem. Soc. 2001,
123, 12191.
10. Frick, J. G., Jr.; Harper, R. J., Jr. Acetals as cross linking reagents for cotton.
J. Appl. Polym. 1984, 29, 1433.
11. Jin, T.-S.; Sun, G.; Li, Y.-W.; Li, T.-S. An efficient and convenient procedure for
the preparation of 1,1-diacetates from aldehydes catalyzed by H2NSO3H. Green
Chem. 2002, 4, 255.
12. Aggen, D. H.; Arnold, J. N.; Hayes, P. D.; Smoter, N. J.; Mohan, R. S. Bismuth
compounds in organic synthesis: Bismuth nitrate catalyzed chemoselective
synthesis of acylals from aromatic aldehydes. Tetrahedron 2004, 60, 3675.
13. Smitha, G.; Reddy, C. S. A facile and efficient ZrCl4-catalyzed conversion of
aldehydes to geminal-diacetates and dipivalates and their cleavage. Tetrahedron
2003, 59, 9571, and references cited therein.
14. Wang, C.; Li, M. A novel and efficient conversion of aldehydes to 1,1-diacetates
catalyzed with FeCl3/SiO2 under microwave irradiation. Synth. Commun. 2002,
32, 3469.
15. Reddy, A. V.; Ravinder, K.; Reddy, V. L. N.; Ravinkanth, V.; Yenkateswarlu, Y.
Amberlyst-15-catalyzed efficient synthesis of 1,1-diacetates from aldehydes. Synth
Commun. 2003, 33, 1531.
16. Firouzabadi, H.; Iranpoor, N.; Nowrouzi, F.; Amani, K. Aluminum dodecatungsto-
phosphate (AlPW12O40) as an efficient heterogeneous inorganic catalyst for the
chemoselective synthesis of geminal diacetates (acylals) under solvent-free con-
ditions. Tetrahedron Lett. 2003, 44, 3951.
17. Heravi, M. M.; Bakhtiari, K.; Taheri, S.; Oskooie, H. A. KHSO4: A catalyst for the
chemoselective preparation of 1,1-diacetates from aldehydes under solvent-free
conditions. Green Chem. 2005, 7, 867.
18. Heravi, M. M.; Taheri, S.; Bakhtiari, K.; Oskooie, H. A. Cupric sulfate pentahy-
drate: A mild and efficient catalyst for the chemoselective synthesis of 1,1-diace-
tates from aldehydes in a solvent-free system. Monatsh. Chem. 2006, in press.
19. Heravi, M. M.; Bakhtiari, K.; Bamoharram, F. F. An efficient and chemoselective
synthesis of acylals from aromatic aldehydes and their regeneration, catalyzed by
12-molybdophosphoric acid. Catal. Commun. 2006, 7, 499.
20. Heravi, M. M.; Derikvand, F.; Bamoharram, F. F. Dodecatungstophosphoric acid
(H3PW12O40): A novel and efficient recyclable catalyst for synthesis of 1,1-diace-
tates from aromatic aldehydes in solvent-free system and their deprotection. Synth.
Commun. 2006, 36, 3109.
21. Freeman, I.; Karcherski, E. M. Preparation and spectral properties of benzylidene
diacetates. J. Chem. Eng. Data. 1977, 22, 355.
22. Jin, T.-S.; Du, G.-Y.; Li, T.-S. An efficient and convenient procedure for the
synthesis of 1,1-diacetates of aldehydes catalyzed by anhydrous ferrous sulfate.
Ind. J. Chem. 1998, 37 (B), 939.
23. Negron, G. E.; Palacios, L. N.; Angeles, D.; Lomas, L.; Gavino, R. A mild and
efficient method for the chemoselective synthesis of acylals from aromatic

1126
M. M. Heravi et al.
aldehydes and their deprotections catalyzed by sulfated zirconia. J. Braz. Chem.
Soc. 2005, 16 (3A), 490.
24. Zhang, Z. H.; Li, T. S.; Fu, C. G. Montmorillonite clay catalysis, part 4: An
efficient and convenient procedure for preparation of 1,1-diacetates from
aldehydes. J. Chem. Res. Synop. 1997, 174.
25. Jin, T. S.; Ma, Y. R.; Sun, X.; Liang, D.; Li, T. S. Facile preparation of 1,1-diace-
tates from aldehydes with acetic anhydride catalyzed by TiO2/SO42–solid
superacid. J. Chem. Res. Synop. 2000, 96.
26. Kochhar, K. S.; Bal, B. S.; Deshpande, R. P.; Rajadhyksha, S. R.; Pinnick, H. W.
Protecting groups in organic synthesis, part 8: Conversion of aldehydes into
geminal diacetates. J. Org. Chem. 1983, 48, 1765.