Tandem and Selective Conversion of Tetrahydropyranyl and Silyl Ethers to Oximes Catalyzed with Trichloroisocyanuric Acid

Article abstract of DOI:10.1080/10426507.2014.990015

Direct and oxidative conversion of tetrahydropyranyl and silyl ethers to oximes is described using trichloroisocyanuric acid (TCCA) as a relatively stable and inexpensive oxidant surprisingly in a catalytic amount and hydroxylamine hydrochloride under solvent-free conditions. Oximes can be synthesized from these protected alcohols in the presence of some other functional groups with excellent chemoselectivity using the present tandem catalytic method.

Full text of DOI:10.1080/10426507.2014.990015

This article was downloaded by: [FU Berlin]
On: 13 May 2015, At: 13:46
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered office: Mortimer House,
37-41 Mortimer Street, London W1T 3JH, UK
Phosphorus, Sulfur, and Silicon and the Related
Elements
Publication details, including instructions for authors and subscription information:
http://www.tandfonline.com/loi/gpss20
Tandem and Selective Conversion of Tetrahydropyranyl
and Silyl Ethers to Oximes Catalyzed with
Trichloroisocyanuric Acid
Ghasem Aghapoura & Zeinab Abbaszadeh
a School of Chemistry, Damghan University, Damghan 36715-364, Iran
Accepted author version posted online: 14 Jan 2015.
Click for updates
To cite this article: Ghasem Aghapour & Zeinab Abbaszadeh (2015): Tandem and Selective Conversion of Tetrahydropyranyl
and Silyl Ethers to Oximes Catalyzed with Trichloroisocyanuric Acid, Phosphorus, Sulfur, and Silicon and the Related Elements,
DOI: 10.1080/10426507.2014.990015
To link to this article: http://dx.doi.org/10.1080/10426507.2014.990015
Disclaimer: This is a version of an unedited manuscript that has been accepted for publication. As a service
to authors and researchers we are providing this version of the accepted manuscript (AM). Copyediting,
typesetting, and review of the resulting proof will be undertaken on this manuscript before final publication of
the Version of Record (VoR). During production and pre-press, errors may be discovered which could affect the
content, and all legal disclaimers that apply to the journal relate to this version also.
PLEASE SCROLL DOWN FOR ARTICLE
Taylor & Francis makes every effort to ensure the accuracy of all the information (the “Content”) contained
in the publications on our platform. However, Taylor & Francis, our agents, and our licensors make no
representations or warranties whatsoever as to the accuracy, completeness, or suitability for any purpose of the
Content. Any opinions and views expressed in this publication are the opinions and views of the authors, and
are not the views of or endorsed by Taylor & Francis. The accuracy of the Content should not be relied upon and
should be independently verified with primary sources of information. Taylor and Francis shall not be liable for
any losses, actions, claims, proceedings, demands, costs, expenses, damages, and other liabilities whatsoever
or howsoever caused arising directly or indirectly in connection with, in relation to or arising out of the use of
the Content.
This article may be used for research, teaching, and private study purposes. Any substantial or systematic
reproduction, redistribution, reselling, loan, sub-licensing, systematic supply, or distribution in any
form to anyone is expressly forbidden. Terms & Conditions of access and use can be found at http://
www.tandfonline.com/page/terms-and-conditions

ACCEPTED MANUSCRIPT
“Tandem Conversion of Protected Alcohols to Oximes”
Tandem and Selective Conversion of Tetrahydropyranyl and Silyl Ethers to Oximes
Catalyzed with Trichloroisocyanuric Acid
Ghasem Aghapour,* Zeinab Abbaszadeh
* School of Chemistry, Damghan University, Damghan 36715-364, Iran. Email:
Gh_Aghapour@du.ac.ir
Abstract: Direct and oxidative conversion of tetrahydropyranyl and silyl ethers to oximes is
described using trichloroisocyanuric acid (TCCA) as a relatively stable and inexpensive oxidant
surprisingly in a catalytic amount and hydroxylamine hydrochloride under solvent-free
conditions. Oximes can be synthesized from these protected alcohols in the presence of some
other functional groups with excellent chemoselectivity using the present tandem catalytic
method.
Keywords: Tetrahydropyranyl ether, Silyl ether, Oxime, Trichloroisocyanuric acid, Tandem
synthesis.
1
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
Introduction
Oximes have useful applications in organic synthesis. These stable compounds may be
served as intermediates for the preparation of nitriles via dehydration,1,2 amides by the
Beckmann rearrangement,3 nitrones,4 hydroximinoyl chlorides,5 nitrile oxides,5 chiral α-sulfinyl
oximes,6 and nitro compounds.7 In addition, oximes have been used as selective α-activating
groups8 and also for the protection of carbonyl groups.9 Some oximes treat as highly active and
effective inhibitors.10,11 Also, oximation is a very efficient and useful way for characterization
and purification of carbonyl compounds. Therefore, the attention of synthetic organic chemists is
directed to a facilitation of oxime synthesis from carbonyl compounds or even other sources.
Oximes are usually prepared via treatment of aldehydes or ketones with hydroxylamine
hydrochloride in a basic aqueous medium with adjustment of pH. In addition, a large number of
other methods have been reported for performing of this transformation.12-14 However, some
methods in this area contain some disadvantages such as low yields, long reaction times, inability
for the preparation of aromatic ketoximes, effluent pollution and tedious work up. Also, as far as
we know the oximes synthesis directly from alcohols have been reported very less than from
aldehydes or ketones especially in a catalytic manner. Two reported methods in this field are the
use of a two step procedure involving substitution with PPh3/DEAD/O-TBS-N-
tosylhydroxylamine in toluene-THF and subsequent treatment with CsF in acetonitrile15 and also
the use of activated MnO2, 4 Å molecular sieves as dehydrating additive and alkoxylamines (and
in certain cases, hydroxylamine itself) as their hydrochloride salts or supported on Amberlyst 15
in CH2Cl2 at reflux for overnight.16 However, these methods do not perform this transformation
in a catalytic manner and use stoichiometric amounts of the reagents or even more for this
2
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
purpose. For example, in the latter work manganese dioxide is used in excess amounts (5-20
equiv.). Furthermore, the use of gold supported on hydroxyapatite (Au/HAP) (HAP,
o
Ca10(PO4)6(OH)2) as catalyst in toluene as solvent at 90 C under O2 bubbling17 and also 1-
methylimidazolium nitrate [Hmim][NO3] as an acidic ionic liquid under microwave irradiation18
have also been reported for performing of this transformation. However, these methods
converting alcohols directly to oximes also suffer from some other disadvantages such as long
reaction times, the use of a two step procedure or reagent that is not easily available, low yields,
tedious work up especially in the case of using MnO2, performing of this transformation in the
acidic conditions and also do not provide chemoselectivity or at least, chemoselectivity of the
method is ambiguous. Finally, as far as we know there is no report in the literature concerning
the tandem catalytic conversion of tetrahydropyranyl and silyl ethers to oximes.
Consequently, there is a need for the development of new methods that are more
convenient for the oxime synthesis especially from tetrahydropyranyl and silyl ethers. On the
other hand, tandem reactions that contain multiple chemical transformations in a single-pot
provide minimal work up and less waste generation in organic synthesis.19 These reactions
involve the advantage that intermediates do not require isolation specially where they are
unstable or difficult to handle. Also, the elimination of volatile organic solvents in organic
syntheses is a most important goal in ‘green’ chemistry. The solvent-free reactions20 have some
advantages such as formation of cleaner products, improved reaction rates, low costs, enhanced
selectivity, simplicity in process and handling and prevent waste solvent generation, hazards, and
toxicity.
3
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
Herein, due to importance of oximes and their synthesis especially from protected
alcohols and on the other hand the importance of tandem and solvent-free reactions and also in
continuation of our previous work on the tandem conversion of benzylic alcohols to oximes
catalyzed with 2,3-dichloro-5,6-dicyanobenzoquinone (DDQ),21 we now report an ease,
chemoselective and tandem conversion of primary and secondary benzylic, nonbenzylic and
cyclic tetrahydropyranyl (THP) and trimethylsilyl (TMS) ethers to oximes using a catalytic
amount of trichloroisocyanuric acid (TCCA) as a relatively stable and inexpensive oxidant in the
presence of hydroxylamine hydrochloride under solvent-free conditions (Scheme 1).
It must be noted that the present method needs to merely a catalytic amount (instead of
stoichiometric amounts) of TCCA in the presence of hydroxylamine hydrochloride for
performing of this tandem transformation.
Results and Discussion
Initially, we took benzyl THP ether as an example and optimized the reaction conditions for its
direct conversion to benzaldoxime using a mixture of trichloroisocyanuric acid (TCCA) and
hydroxylamine hydrochloride (NH3OHCl). The results are shown in Table 1.
As shown in this table, this reaction did not provide satisfactory results using TCCA (3
mol %) and NH3OHCl (1.2 eq.) under solvent-free conditions even at 110oC. In this case,
benzaldoxime was produced in 50% yield after 40 min (Table 1, entry 1). The yield and rate of
this reaction was increased with increasing of TCCA (Table 1, entry 2). On the other hand,
decreasing of temperature caused to decrease of the yield and rate of this reaction so that it was
completely unsuccessful at room temperature (Table 1, entries 3, 4 and 5). Also, this reaction
4
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
was studied in refluxing CH2Cl2 and CH3CN. This study showed that the operation of this
reaction in these solvents under reflux condition does not provide satisfactory results compared
to under solvent-free condition (Table 1, please compare entries 6 and 7 with 2). Finally, the use
o
of TCCA/ NH3OHCl (0.05:1.2) under solvent-free condition at 110 C (Table 1, entry 2) was
selected as the optimized reaction conditions for this transformation and applied for conversion
of other tetrahydropyranyl ethers directly to their corresponding oximes. The results are shown in
Table 2. In the next step, we extended the present method on the silyl ethers for their conversion
o
directly to oximes. However, the optimized reaction temperature was determined at 100 C in
this case. The results are shown in Table 3.
As shown in these tables, primary and secondary benzylic and nonbenzylic, allylic and
cyclic tetrahydropyranyl and trimethylsilyl ethers are directly converted to the corresponding
oximes in moderate to generally excellent yields using a catalytic amount of TCCA (5 mol %) in
o
the presence of hydroxylamine hydrochloride (1.2 eq.) at 110 and 100 C respectively under
solvent-free conditions. The present tandem catalytic method can also be considered as a way for
characterization of the above mentioned types of THP and TMS ethers. In addition, these tables
show that THP ethers are converted to oximes generally faster than TMS ethers. In addition, for
obtaining deeper insight into the applicability, selectivity and limitations of this new method, the
possibility of the conversion of 4-fluorobenzyl THP or TMS ether to 4-fluorobenzaldoxime was
studied in the presence of some other functional groups in different binary mixtures. For this
purpose, a mixture of TCCA/ NH3OHCl (0.05:1.2) was prepared under solvent-free conditions in
o
an oil bath at 110 or 100 C followed by addition of 4-fluorobenzyl THP or TMS ether
5
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
respectively and other organic compound (1:1). The conversion yields obtained for these
selective reactions of different binary mixtures are shown in Table 4.
As shown in this Table, it was found that aliphatic tetrahydropyranyl and trimethylsilyl
ethers can be directly converted to their corresponding oximes in the presence of aromatic ones,
epoxides, carboxylic esters or acids, and aldehydes with excellent chemoselectivity using the
present method. In addition, benzylic tetrahydropyranyl or trimethylsilyl ethers containing
electron withdrawing group at phenyl ring can be efficiently converted to oximes in the presence
of benzylic THP or TMS ethers containing electron donating group with excellent
chemoselectivity via the present method (Table 4, entry 6).
Experimental
Solvents, reagents and chemicals were obtained from Merck (Germany) and Fluka
(Switzerland) Chemical Companies. Tetrahydropyranyl and trimethylsilyl ethers were prepared
according to the literature.22 Products are known compounds21, 23 and were characterized by
comparison of their physical or spectral data with authentic samples. Fourier transform-infrared
(FT-IR) spectra were recorded on a Perkin-Elmer RXI spectrophotometer. Nuclear magnetic
resonance (NMR) spectra were recorded on a Brucker Avance DRX-400 spectrometer. Thin-
layer chromatography (TLC) was carried out on silica-gel 254 analytical sheets obtained from
Fluka.
Typical procedure for the conversion of 4-chlorobenzyl tetrahydropyranyl ether to 4-
chlorobenzaldehyde oxime using NH3OHCl catalyzed with TCCA
6
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
Hydroxylamine hydrochloride NH3OHCl (0.083 g, 1.2 mmol) was added to a flask
containing 4-chlorobenzyl tetrahydropyranyl ether (0.226 g, 1 mmol) and TCCA (0.012 g, 0.05
o
mmol) under solvent-free conditions in an oil bath at 110 C. The mixture was stirred until TLC
showed the completion of the reaction (60 min). Dichloromethane (5 mL) was added to the
reaction mixture after cooling to room temperature. The reaction mixture was filtered and then
the solvent was evaporated. The crude mixture was subjected to column chromatography on
silica gel 60 (0.063-0.200 mm) using petroleum benzine-ethyl acetate (30:1) as eluent to give 4-
chlorobenzaldehyde oxime (0.148 g) in 95% yield; 1H NMR (CDCl3, 400 MHz): δ 7.44-7.46 (m,
2H), 7.59-7.61 (m, 2H), 8.15 (s, 1H), 11.39 (br, 1H) ppm; 13C NMR (CDCl3, 100.6 MHz): δ
128.5, 129.2, 132.4, 134.2,147.6 ppm.
The reaction conditions for the tandem conversion of TMS ethers to the corresponding
oximes is the same as to THP ethers via the present method except the reaction temperature
which is adjusted at 100 oC.
Conclusions
In conclusion, in spite of many reports in the literature about the oxidation of
tetrahydropyranyl and silyl ethers to carbonyl compounds with various oxidants in stoichiometric
amounts or even more, the present investigation has demonstrated that the use of a catalytic
amount of TCCA in the presence of hydroxylamine hydrochloride under solvent-free conditions
offers a simple and tandem method for the conversion of primary and secondary benzylic and
nonbenzylic tetrahydropyranyl and trimethylsilyl ethers to their corresponding oximes in good to
excellent yields. Oximes can be synthesized from these ethers even in the presence of some other
functional groups with excellent chemoselectivity via the present method. Commercially
7
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
availability, relatively cheapness and easy to handle of the catalyst, easy work up, relatively low
reaction times especially in the case of THP ethers, avoiding the use of any additives such as
molecular sieves and applicability for the conversion of both primary and secondary these ethers
can be considered as the other significant advantages of the present tandem method. In addition
to synthetic importance, this one-pot oximation method can be used as a way for characterization
of these ethers.
Also, it must be noted that the present method belongs to green chemistry because: 1) It
contains a tandem procedure. 2) It is operated under solvent-free conditions. 3) It needs to a
catalytic amount of TCCA for operation.
Acknowledgments
We gratefully acknowledge the support of this work by the Damghan University
Research Council.
8
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
References
[1] Aghapour, G.; Amirabadi, M. Indian J. Chem. Sec. B 2007, 46B, 649-652.
[2] Iranpoor, N.; Firouzabadi, H.; Aghapour, G. Synth. Commun. 2002, 32, 2535-2541.
[3] Donaruma, L. G.; Helst, W. Z. Org. React. 1960, 11, 1.
[4] (a) Smith, P. A.; Robertson, J. E. J. Am. Chem. Soc. 1962, 84, 1197-1204; (b) Buehler,
E. J. Org. Chem. 1967, 32, 261-265; (c) Schoenewaldt, E. F.; Kinnel, R. B.; Paul, D. J.
Org. Chem. 1968, 33, 4270-4272.
[5] (a) Chiang, Y. H. J. Org. Chem. 1971, 36, 2146-2155; (b) Liu, K. C.; Shelton, B. R.;
Howe, R. K. J. Org. Chem. 1980, 45, 3916-3918.
[6] Hajipour, A. R.; Mahboubghah, N. J. Chem. Res. (S) 1998, 122-123.
[7] Dave, P. R.; Forohar, F.; Axenrod, T.; Das, K. K.; Qi, L.; Watnick, C.; Yazdekhasti, H.
J. Org. Chem. 1996, 61, 8897-8903.
[8] Whitesell, J. K.; Whitesell, M. A. Synthesis 1983, 517-536.
[9] Shinada, T.; Yoshihara, K. Tetrahedron Lett. 1995, 36, 6701-6704.
[10] Ley, J. P.; Bertram, H. J. Bioorgan. Med. Chem. 2001, 9, 1879-1885.
[11] Shen, C.; Sigman, D. S. Arch. Biochem. Biophys. 1991, 286, 596-603.
[12] (a) Li, J. T.; Li, X. L.; Li, T. S. Ultrason. Sonochem. 2006, 13, 200-202; (b) Guo, J. J.;
Jin, T. S.; Zhang, S. L.; Li, T. S. Green Chem. 2001, 3, 193-195; (c) Sharghi, H.;
Hosseini Sarvari, M. J. Chem. Res. (S) 2000, 24-25.
[13] (a) Niknam, K.; Karimi, B.; Kiasat, A. R. Bull. Korean Chem. Soc. 2005, 26, 975-978;
(b) Eshghi, H.; Alizadeh, M. H.; Davamdar, E. J. Korean Chem. Soc. 2008, 52, 52-56;
9
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
(c) Damljanovic, I.; Vukicevic, M.; Vukicevic, R. D. Monatsh. für Chem. 2006, 137,
301-305.
[14] (a) Xia, J. J.; Wang, G. W. Molecules 2007, 12, 231-236; (b) Zang, H.; Wang, M.;
Cheng, B. W.; Song, J. Ultrason. Sonochem. 2009, 16, 301-303.
[15] Kitahara, K.; Toma, T.; Shimokawa, J.; Fukuyama, T. Org. Lett. 2008, 10, 2259-2261.
[16] Kanno, H.; Taylor, R. J. K. Synlett 2002, 1287-1290.
[17] Sun, H.; Su, F. Z.; Ni, J.; Cao, Y.; He, H. Y.; Fan, K. N. Angew. Chem. Int. Ed. 2009,
48, 4390-4393.
[18] Mirjafari, A.; Mobarrez, N.; O’Brien, R. A. ; Davis Jr, J. H. ; Noei, J. C. R. Chimie
2011, 14, 1065-1070.
[19] Wasilke, J. C.; Obrey, S. J.; Baker, T.; Bazan, G. C. Chem. Rev. 2005, 105, 1001-1020.
[20] Tanaka, K.; Toda, F. Chem. Rev. 2000, 100, 1025-1074.
[21] Aghapour, G.; Mohamadian, S. Bull. Korean Chem. Soc. 2012, 33, 1209-1212.
[22] (a) Yang, J.; Zhang, X. ; Yi Liu, W. Chem. Lett. 2008, 19, 893-896; (b) Karimi, B.;
Golshani, B. J. Org. Chem. 2000, 65, 7228-7230.
[23] Vogel, A. Vogel’s Practical Organic Chemistry, including qualitative organic analysis,
Fourth ed.; Longman: London and New York, 1978.
10
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
Table 1: Conversion of benzyl THP ether to benzaldoxime using a mixture of TCCA as catalyst
and NH3OHCl in various conditions.
Entry
Solvent
Molar ratioa Temp.(oC) Time (min)
Yield (%)
1
2
3
4
5
6
7
-
1:0.03:1.2
1:0.05:1.2
1:0.05:1.2
1:0.05:1.2
1:0.05:1.2
1:0.05:1.2
1:0.05:1.2
110
110
90
40
30
50
98
90
90
0
-
-
150
420
90
-
70
-
r.t.
CH2Cl2
CH3CN
reflux
reflux
90
0
90
70
a Molar ratio is related to THP ether:TCCA:NH3OHCl.
11
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
Table 2: Conversion of THP ethers to oximes using a catalytic amount of TCCA (0.05 equiv.)
and NH3OHCl (1.2 equiv.) under solvent-free conditions at 110 oC.
Entry
THP Ether
Oxime
Time
(min)
Yield
(%)a
1
2
p-Cl-C6H4CH2OTHP
m-Cl-C6H4CH2OTHP
o,p-Cl2-C6H3CH2OTHP
p-Br-C6H4CH2OTHP
p-F-C6H4CH2OTHP
p-Cl-C6H4CH=NOH
m-Cl-C6H4CH=NOH
o,p-Cl2-C6H3CH=NOH
p-Br-C6H4CH=NOH
p-F-C6H4CH=NOH
60
95
92
96
92
97
51
98
78
63
90
97
90
30
3
40
4
30
5
30
6
p-CH3O-C6H4CH2OTHP
C6H5CH2OTHP
p-CH3O-C6H4CH=NOH
C6H5CH=NOH
70
7
30
8
p-tBu-C6H4CH2OTHP
C6H5CH=CHCH2OTHP
C6H5CH(CH3)OTHP
C6H5CH(CH3)CH2OTHP
CH3(CH2)5CH(CH3)OTHP
p-tBu-C6H4CH=NOH
C6H5CH=CHCH=NOH
C6H5C(CH3)=NOH
75
9
45
10
11
12
120
90
C6H5CH(CH3)CH=NOH
CH3(CH2)5C(CH3)=NOH
120
OTHP
OTHP
NOH
NOH
13
14
100
60
79
95
a Isolated yields.
12
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
Table 3: Conversion of trimethylsilyl ethers to oximes using a catalytic amount of TCCA (0.05
equiv.) and NH3OHCl (1.2 equiv.) under solvent-free conditions at 100 oC.
Entry
Silyl Ether
Oxime
Time
(h)
Yield
(%)a
1
2
p-Cl-C6H4CH2OSi(CH3)3
m-Cl-C6H4CH2OSi(CH3)3
o,p-Cl2-C6H3CH2OSi(CH3)3
p-Br-C6H4CH2OSi(CH3)3
p-F-C6H4CH2OSi(CH3)3
p-CH3O-C6H4CH2OSi(CH3)3
C6H5CH2OSi(CH3)3
p-Cl-C6H4CH=NOH
m-Cl-C6H4CH=NOH
o,p-Cl2-C6H3CH=NOH
p-Br-C6H4CH=NOH
p-F-C6H4CH=NOH
p-CH3O-C6H4CH=NOH
C6H5CH=NOH
4.75
1.5
2
92
95
90
96
95
52
97
95
71
98
90
80
3
4
1.5
1
5
6
4
7
3
8
p-tBu-C6H4CH2OSi(CH3)3
C6H5CH=CHCH2OSi(CH3)3
C6H5CH(CH3)OSi(CH3)3
C6H5CH(CH3)CH2OSi(CH3)3
p-tBu-C6H4CH=NOH
C6H5CH=CHCH=NOH
C6H5C(CH3)=NOH
2
9
3.25
4.5
1.5
2.5
10
11
12
C6H5CH(CH3)CH=NOH
CH3(CH2)5CH(CH3)OSi(CH3)3 CH3(CH2)5C(CH3)=NOH
OSi(CH3)3
OSi(CH3)3
NOH
NOH
13
14
4.25
3.25
90
73
a Isolated yields.
13
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
Table 4: Selectivities in the conversion of THP and TMS ethers to oximes using a catalytic
o
o
amount of TCCA (0.05 equiv.) and NH3OHCl (1.2 equiv.) at 110 C and 100 C respectively
under solvent-free conditions.
Entry
1
Selectivity
100%
100%
p-F-C6H4CH2OX
p-F-C6H4CH=NOH
30 min (X= THP)
or 60 min (X= Si(CH3)3)
C6H5OX
C6H5OX
100%
100%
p-F-C6H4CH=NOH
p-F-C6H4CH2OX
30 min (X= THP)
O
2
O
C6H5O
C6H5O
100%
p-F-C6H4CH=NOH
p-F-C6H4CH2OX
30 min (X= THP)
3
4
or 120 min (X= Si(CH3)3)
100%
100%
C6H5CO2CH2CH3
C6H5CO2CH2CH3
p-F-C6H4CH=NOH
p-F-C6H4CH2OX
30 min (X= THP)
or 60 min (X= Si(CH3)3)
100%
100%
C6H5CO2H
C6H5CO2H
p-F-C6H4CH=NOH
p-F-C6H4CH2OX
30 min (X= THP)
5
or 60 min (X= Si(CH3)3)
100%
C6H5CH2CH2CHO
C6H5CH2CH2CHO
14
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
p-F-C6H4CH=NOH 100%
p-CH3O-C6H4CH2OX
p-F-C6H4CH2OX
40 min (X= THP)
or 60 min (X= Si(CH3)3)
6
p-CH3O-C6H4CH2OX
80% (X= THP)
90% (X= Si(CH3)3)
15
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
TCCA (5 mol%)/
NH3OHCl (1.2 eq.)
or RR'C=NOH
or RR'CHOX
CR=NOH
CHROX
Solvent-free; 100-110 oC
Y
Y
51-98%
X= THP or Si(CH3)3
R= H, alkyl; R'= alkyl
Y= H, F, Cl, Br, CH3O, tButyl
Scheme 1: Tandem conversion of primary and secondary tetrahydropyranyl and silyl ethers to
oximes using a catalytic amount of TCCA in the presence of hydroxylamine hydrochloride under
solvent-free conditions.
16
ACCEPTED MANUSCRIPT