Cu(NO3)2 · 3 H2O as an efficient reagent for the chemoselective trimethylsilylation of primary alcohols and oxidation of trimethylsilyl ethers

Article abstract of DOI:10.1080/10426507.2011.614300

Cu(NO₃)₂ · 3 H₂O can be used as an efficient reagent for the chemoselective trimethylsilylation of primary benzylic and aliphatic alcohols with hexamethyldisilazane (HMDS). This reagent is also able to oxidize the obtained trimethylsilyl ethers to the corresponding carbonyl compounds in the presence of wet SiO₂ and KBr. In this study, all reactions are performed in the absence of a solvent and good-to-high yields are obtained.

Full text of DOI:10.1080/10426507.2011.614300

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Cu(NO3)2 · 3 H2O as an Efficient
Reagent for the Chemoselective
Trimethylsilylation of Primary Alcohols
and Oxidation of Trimethylsilyl Ethers
F. Shirini a & M. Mashhadi-Nejad a
a Department of Chemistry, College of Science , University of
Guilan , Rasht , 41335 , Iran
Published online: 31 Jan 2012.
To cite this article: F. Shirini & M. Mashhadi-Nejad (2012) Cu(NO3)2 · 3 H2O as an Efficient
Reagent for the Chemoselective Trimethylsilylation of Primary Alcohols and Oxidation of
Trimethylsilyl Ethers, Phosphorus, Sulfur, and Silicon and the Related Elements, 187:3, 376-381, DOI:
10.1080/10426507.2011.614300
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Phosphorus, Sulfur, and Silicon, 187:376–381, 2012
Copyright ꢀC Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426507.2011.614300
Cu(NO3)2 · 3 H2O AS AN EFFICIENT REAGENT
FOR THE CHEMOSELECTIVE TRIMETHYLSILYLATION
OF PRIMARY ALCOHOLS AND OXIDATION
OF TRIMETHYLSILYL ETHERS
F. Shirini and M. Mashhadi-Nejad
Department of Chemistry, College of Science, University of Guilan,
Rasht 41335, Iran
GRAPHICAL ABSTRACT
.
Cu(NO3)2 3 H2O (0.75 mmol), HMDS (1.3 mmol)
PhCH2OH
PhCH2OTMS
Solvent-free, r.t., 20 min, 91%
Abstract Cu(NO3)2 · 3 H2O can be used as an efficient reagent for the chemoselective
trimethylsilylation of primary benzylic and aliphatic alcohols with hexamethyldisilazane
(HMDS). This reagent is also able to oxidize the obtained trimethylsilyl ethers to the corre-
sponding carbonyl compounds in the presence of wet SiO2 and KBr. In this study, all reactions
are performed in the absence of a solvent and good-to-high yields are obtained.
Keywords Cu(NO3)2 · 3 H2O; alcohols; trimethylsilylation; oxidation; solvent-free conditions
INTRODUCTION
Hexamethyldisilazane (HMDS) is one of the most important reagents widely used
for the protection of alcoholic hydroxy groups during a multistep synthesis. A num-
ber of reagents have been reported for the promotion of silylation of alcohols with
HMDS, including sulfonic acid,1 K-10 montmorillonite,2 zirconium sulfophenyl phos-
phonate,3 Me3SiCl,4 silica chloride,5 Al(HSO4)3,6 Fe(HSO4)3,7 ZrCl4,8 tungstophospho-
ric acid,9 saccharin sulfonic acid,10 sulfonic acid-functionalized ordered nanoporous sil-
ica,11 trichloroisocyanuric acid,12 cupric sulfate penthydrate,13 copper triflate,14 mono- and
dibromo-5,5-diethylbarbutiric acids,15 1,3-dibromo-5,5-diethylbarbutiric acid,16 lanthanum
trichloride,17 tribromomelamine,18 PhMe3N+Br3− 19 niobium (V) chloride,20 N,Nꢁ-di-iodo-
,
N,Nꢁ-1,2-ethanediyl bis(p-toluenesulfonamide),21 p-toluenesulfonyl chloride,22 and silica-
supported zinc chloride.23 However, some of the reported methods suffer from one or more
of the following disadvantages: long reaction times, low selectivity, forceful conditions,
tedious work-up procedure, and use of toxic, expensive, or moisture-sensitive reagents.
Hence, the introduction of new procedures to circumvent these problems is still in demand.
Received 7 June 2011; accepted 10 August 2011.
We are thankful to the University of Guilan Research Councils for the partial support of this work.
Address correspondence to F. Shirini, Department of Chemistry, College of Science, University of Guilan,
Rasht 41335, Iran. E-mail: shirini@guilan.ac.ir
376

CHEMOSELECTIVE TRIMETHYLSILYLATION AND OXIDATION OF ETHERS
377
In 2007, Heravi et al. reported that Cu(NO3)2 · 3 H2O is able to efficiently catalyze the
protection of aldehydes as the corresponding 1,1-diacetates.24 Motivated by this study and
in continuation of our ongoing research program on the development of new methods for
the protection of hydroxy groups,4–8,10 we have investigated the applicability of Cu(NO3)2·
3 H2O in the promotion of trimethylsilylation of alcohols with HMDS.
RESULTS AND DISCUSSION
Initially, benzyl alcohol was chosen as a model substrate for the silylation reaction.
Optimization of the reaction conditions showed that the best results were obtained when
benzyl alcohol was treated with 1.3 equivalents of HMDS in the presence of 0.75 equivalent
of Cu(NO3)2 · 3 H2O in the absence of a solvent at room temperature (20 min, 91% isolated
yield) (Scheme 1).
.
Cu(NO3)2 3 H2O (0.75 mmol), HMDS (1.3 mmol)
PhCH2OH
PhCH2OTMS
Solvent-free, r.t., 20 min, 91%
Scheme 1
After optimization of the reaction conditions, different types of primary benzylic and
aliphatic alcohols were subjected to trimethylsilylation under the determined conditions.
As shown in Table 1, the corresponding trimethylsilyl ethers were obtained in excellent
yields. No elimination and rearrangement byproducts were observed at all. Secondary and
tertiary alcohols and phenols silylate slower than primary alcohols using this method and
the reaction is in most cases incomplete (Table 1, entries 14–20). In addition, amines and
thiols are resistant to this reagent and remained unchanged in the reaction mixture (Table
1, entries 21–23). Therefore, this methodology shows selectivity and is suitable for the
selective trimethylsilylation of primary benzylic and aliphatic alcohols in the presence of
the abovementioned substrates (Table 1, entries 24–27).
Although the actual role of Cu(NO3)2 · 3 H2O is not clear, the mechanism shown in
Scheme 2 seems to be the most probable one.
2ROH
2ROTMS
Cu(NO3)2 . 3 H2O
H3N. Cu(NO3)2 . 3 H2O
(Me3Si)2NH
[(Me3Si)2NH] [Cu(NO3)2 . 3 H2O]
(Me3Si)2NH
NH3
Scheme 2
In order to show the efficiency of the proposed method, Table 2 compares some of
the results obtained by our method with some of those reported in the literature.
Recently, KBr was used as an efficient reagent for the promotion of oxidation of
alcohols with periodic acid and iodic acid in the presence of wet SiO2.27 Our studies
revealed that the oxidation of the trimethylsilyl ethers obtained occurs efficiently using
Cu(NO3)2 · 3 H2O in the presence of KBr/wet SiO2 under the conditions presented in

378
F. SHIRINI AND M. MASHHADI-NEJAD
Table 1 Trimethylsilylation of alcohols catalyzed by Cu(NO3)2 · 3 H2Oa,b
Time Yield
Entry
1
Substrate
Product
(h)
(%)
References
PhCH2OH
PhCH2OTMS
0.3
91
Ghorbani-Choghamarani
et al. (2008)18
2
3
4
5
6
2-ClC6H4CH2OH
4-ClC6H4CH2OH
3,4-ClC6H3CH2OH
4-BrC6H4CH2OH
2-MeC6H4CH2OH
2-ClC6H4CH2OTMS
4-ClC6H4CH2OTMS
3,4-ClC6H3CH2OTMS
4-BrC6H4CH2OTMS
2-MeC6H4CH2OTMS
2.25
0.5
88
90
87
92
90
Zareyee and Karimi
(2007)11
Ghorbani-Choghamarani
et al. (2008)18
Zareyee and Karimi
(2007)11
Ghorbani-Choghamarani
et al. (2008)18
0.6
0.75
0.8
Zareyee and Karimi
(2007)11
7
8
4-Me3CC6H4CH2OH
2-NO2C6H4CH2OH
4-Me3CC6H4CH2OTMS
2-NO2C6H4CH2OTMS
1.3
3
91
85
Rajagopal et al. (2009)25
Zareyee and Karimi
(2007)11
9
4-NO2C6H4CH2OH
4-NO2C6H4CH2OTMS
2
87
Ghorbani-Choghamarani
et al. (2008)18
10
11
4-MeOC6H4CH2OH
PhCH2CH2OH
4-MeOC6H4CH2OTMS
PhCH2CH2OTMS
0.6
0.3
90
91
Firuozabadi et al. (2002)9
Ghorbani-Choghamarani
et al. (2008)18
12
13
PhCH2CH2CH2OH
Ph2CHOH
PhCH2CH2CH2OTMS
Ph2CHOTMS
0.5
6
90
50
Firuozabadi et al. (2002)9
Ghorbani-Choghamarani
et al. (2008)18
14
15
16
5
6
6
50
60
50
Firuozabadi et al. (2002)9
OH
OH
OTMS
OTMS
Ghorbani-Choghamarani
et al. (2008)18
Zareyee and Karimi
(2007)11
OH
OTMS
17
18
Ph3COH
PhOH
Ph3COTMS
PhOTMS
4
7
0c
80
—
Ghorbani-Choghamarani
et al. (2008)18
Kadam and Kim (2009)26
Firuozabadi et al. (2002)9
19
20
4-Me2CHC6H4OH
4-Me2CHC6H4OTMS
3
7
90
80
OH
OTMS
21
22
23
24
4-BrC6H4SH
C6H5SH
C6H5NH2
2-ClC6H4CH2OH + Ph3COH
4-BrC6H4STMS
C6H5STMS
C6H5NHTMS
2-ClC6H4CH2OTMS + Ph3COTMS
3
3
3
3
0c
0c
0c
—
—
—
—
100d
+
0d
25
26
27
28
PhCH2OH + PhOH
PhCH2OTMS + PhOTMS
0.3 90d
+
—
—
—
—
10d
100d +
0d
2-ClC6H4CH2OH + C6H5SH
2-ClC6H4CH2OH + C6H5NH2
2-ClC6H4CH2OTMS + C6H5STMS
2-ClC6H4CH2OTMS + C6H5NHTMS
2
3
90d +
10d
0.4
100d
NHCH2CH2OTM
NHCH2CH2OH
aProducts were identified spectroscopically and also by the conversion of the silyl ethers to the corresponding
alcohols.
bIsolated yields.
cStarting material was recovered unchanged.
dConversion (GC).

CHEMOSELECTIVE TRIMETHYLSILYLATION AND OXIDATION OF ETHERS
379
Table 2 Cu(NO3)2 · 3 H2O-catalyzed trimethylsilylation of benzyl alcohol in comparison with other methods
reported in the literature
Entry
Catalyst/Condition
Solvent Time (min) Yield (%)
References
1
2
3
Fe(HSO4)3; reflux
H3PW12O40; 55–60 ◦C
Sulfonic acid-functionalized ordered CH2Cl2
nanoporous silica; r.t.
TCCA; r.t.
1,3-Dibromo-5,5-diethylbarbituric
acid; r.t.
CH3CN
Neat
100
23
80
70
90
99
Shirini et al. (2008)7
Firuozabadi et al. (2002)9
Zareyee and Karimi (2007)11
4
5
CH2Cl2
Neat
240
30
90
95
Khazaei et al. (2007)12
Khazaei et al. (2007)16
6
7
LaCl3; r.t.
Cu(NO3)2 · 3 H2O; r.t.
CH2Cl2
Neat
180
20
91
91
Narsaiah (2007)17
This work
Scheme 3. All reactions are performed in the absence of a solvent at 90 ◦C and excellent
yields are obtained (Table 3).
On the basis of the results obtained and literature reports27,28 a mechanism for the
reaction can be suggested, which is shown in Scheme 4.
Scheme 3
Scheme 4
In conclusion, we have developed a mild, efficient, and chemoselective method for
trimethylsilylation of primary benzylic and aliphatic alcohols and for oxidation of the
trimethylsilyl ethers obtained. High yields of the products, easy and clean work-up, and
solvent-free reaction conditions are important advantages of this method, which make this
procedure a useful and attractive addition to the currently available methods.
EXPERIMENTAL
Trimethylsilylation of Primary Alcohols: General Procedure
A mixture of the substrate (1 mmol), Cu(NO3)2 · 3 H2O (0.75 mmol, 0.181 g), and
HMDS (1.3 mmol, 0.21 g) was shaken at room temperature for the specified time. The
progress of the reaction was monitored by TLC. After completion of the reaction, the

380
F. SHIRINI AND M. MASHHADI-NEJAD
Table 3 Oxidation of trimethylsilyl ethersa,b
Entry
Substrate
PhCH2OTMS
2-ClC6H4CH2OTMS
4-ClC6H4CH2OTMS
3,4-ClC6H3CH2OTMS
2-BrC6H4CH2OTMS
4-BrC6H4CH2OTMS
2-MeC6H4CH2OTMS
4-Me3CC6H4CH2OTMS 4-Me3CC6H4CHO
2-NO2C6H4CH2OTMS
4-NO2C6H4CH2OTMS
4-MeOC6H4CH2OTMS 4-MeOC6H4CHO
PhCH2CH2OTMS
Product
PhCHO
2-ClC6H4CHO
4-ClC6H4CHO
3,4-ClC6H3CHO
2-BrC6H4CHO
4-BrC6H4CHO
2-MeC6H4CHO
Time (h) Yield (%)
References
1
2
3
4
5
6
7
8
9
10
11
12
13
0.2
0.3
0.25
0.7
0.75
0.4
0.3
0.5
2.5
1.5
0.25
1
91
88
92
90
87
91
90
87
85
87
70
86
88
Zolfigol et al. (2007)27
Gholizadeh et al. (2004)29
Zolfigol et al. (2007)27
Zolfigol et al. (2007)27
Gholizadeh et al. (2004)29
Zolfigol et al. (2007)27
Bagherzadeh (2003)30
Gholizadeh et al. (2004)29
Gholizadeh et al. (2004)29
Zolfigol et al. (2007)27
Zolfigol et al. (2007)27
Zolfigol et al. (2007)27
Tamami and Yeganeh (1999)31
2-NO2C6H4CHO
4-NO2C6H4CHO
PhCH2CHO
PhCH2CH2CHO
PhCH2CH2CH2OTMS
1.7
aProducts were identified spectroscopically.
bIsolated yields.
mixture was triturated with CH2Cl2 (10 mL) and then filtered. Evaporation of the solvent
under reduced pressure gave almost pure product. Further purification was carried out using
bulb-to-bulb distillation under reduced pressure, vacuum distillation, or recrystallization to
afford pure silyl ether.
Oxidation of Trimethylsilyl Ethers: General Procedure
A mixture of the substrate (1 mmol), wet SiO2 (0.5 g, 50% w:w), KBr (0.35 mmol,
◦
0.042 g), and Cu(NO3)2 · 3 H2O (1 mmol, 0.241 g) was heated in an oil bath (90 C).
The progress of the reaction was monitored by TLC. After completion of the reaction, the
mixture was triturated with CH2Cl2 (5 mL) and then filtered. The solid residue was washed
with CH2Cl2 (5 mL). The filtrate was washed with a saturated solution of NaHCO3 and H2O
and dried over MgSO4. Evaporation of the solvent followed by column chromatography on
silica gel gave the corresponding carbonyl compounds in excellent yields.
REFERENCES
1. Goldschmidt, A. G. T. German Patent 2 758884.
2. Zhang, Z. H.; Li, T. S.; Yang, F.; Fu, C. G. Synth. Commun. 1998, 28, 3105–3114.
3. Curini, M.; Epifano, F.; Marcotullio, M. C.; Rosati, O.; Costantino, U. Synth. Commun. 1999,
29, 541–546.
4. Gautret, P.; El-Ghamarti, S.; Legrand, A.; Couturier, D.; Rigo, B. Synth. Commun. 1996, 26,
707–713.
5. Shirini, F.; Zolfigol, M. A.; Mohammadi, K. Phosphorus Sulfur Silicon Relat. Elem. 2003, 178,
1567–1570.
6. Shirini, F.; Zolfigol, M. A.; Abedini, M. Bull. Chem. Soc. Jpn. 2005, 78, 1982–1985.
7. Shirini, F.; Zolfigol, M. A.; Abri, A. Monatsh. Chem. 2008, 139, 17–20.
8. Shirini, F.; Mollarazi, E. Catal. Commun. 2007, 8, 1393–1396.
9. Firuozabadi, H.; Iranpoor, N.; Amani, K.; Nowrouzi, F. J. Chem. Soc. Perkin Trans 1 2002,
2601–2604.

CHEMOSELECTIVE TRIMETHYLSILYLATION AND OXIDATION OF ETHERS
381
10. Shirini, F.; Zolfigol, M. A.; Abedini, M. Monatsh. Chem. 2009, 140, 61–64.
11. Zareyee, D.; Karimi, B. Tetrahedron Lett. 2007, 48, 1277–1280.
12. Khazaei, A.; Zolfigol, M. A.; Rostami, A.; Ghorbani Choghamarani, A. Catal. Commun. 2007,
8, 543–547.
13. Akhlaghinia, B.; Tavakoli, S. Synthesis 2005, 1775–1778.
14. Firouzabadi, H.; Iranpoor, N.; Sobhani, S.; Gassemipour, S.; Amoozgar, Z. Tetrahedron Lett.
2003, 44, 891–893.
15. Khazaei, A.; Zolfigol, M. A.; Tanbakouchian, Z.; Shiri, M.; Rostami, A. J. Braz. Chem. Soc.
2007, 18, 239–242.
16. Khazaei, A.; Zolfigol, M. A.; Tanbakouchian, Z.; Shiri, M.; Niknam, K.; Saien, J. Catal. Commun.
2007, 8, 917–920.
17. Narsaiah, A. V. J. Organomet. Chem. 2007, 692, 3614–3617.
18. Ghorbani-Choghamarani, A.; Zolfigol, M. A.; Hajjami, M.; Jafari, S. J. Chin. Chem. Soc. 2008,
55, 1208–1213.
19. Ghorbani-Choghamarani, A.; Cheraghi-Fathabad, N. Chin. J. Catal. 2010, 319, 1103–1106.
20. Hou, J. T.; Chen, H. L.; Zhang, Z. H. Phosphorus Sulfur Silicon Relat. Elem. 2011, 186, 88–93.
21. Ghorbani-Vaghei, R.; Malaekehpoor, S. M. Phosphorus Sulfur Silicon Relat. Elem. 2010, 185,
582–587.
22. Khazaei, A.; Rostami, A.; Mamtashlo, F. Phosphorus Sulfur Silicon Relat. Elem. 2009, 184,
2288–2296.
23. Shaterian, H. R.; Khorami, F.; Doostmahammadi, R.; Amirzadeh, A. Ghashang, M. Phosphorus
Sulfur Silicon Relat. Elem. 2009, 184, 2227–2237.
24. Heravi, M. M.; Bakhtiari, K.; Tehrani, M. H.; Oskooie, H. A. Synth. Commun. 2007, 37,
1121–1126.
25. Rajagopal, G.; Lee, H.; Kim, S. S. Tetrahedron 2009, 65, 4735–4741.
26. Kadam, S. T.; Kim, S. S. J. Organomet. Chem. 2009, 694, 2562–2566.
27. Zolfigol, M. A.; Shirini, F.; Ghorbani-Choghamarani, A.; Kolvari, E. J. Mol. Catal. A: Chem.
2007, 265, 272–275.
28. Desai, U. V.; Pore, D. M.; Tamhankar, B. V.; Jadhav, S. A.; Wadgaonkar, P. P. Tetrahedron Lett.
2006, 47, 8559–8561.
29. Gholizadeh, M.; Mohammadpoor-Baltork, I.; Kharamesh, B. Bull. Korean Chem. Soc. 2004, 25,
566–568.
30. Bagherzadeh, M. Tetrahedron Lett. 2003, 44, 8943–8945.
31. Tamami, B.; Yeganeh, H. Eur. Poly. J. 1999, 35, 1445–1450.