Triphenylphosphine/2,3-dichloro-5,6-dicyanobenzoquinone in the presence of n-Bu4NN3 is a useful system for efficient conversion of tetrahydropyranyl (THP) ethers to their corresponding alkyl azides

Article abstract of DOI:10.1080/104265090884292

Triphenylphosphine/2,3-dichloro-5,6-dicyanobenzoquinone/tetrabutylammonium azide was used as an efficient system in conversion of tetrahydropyranyl ethers to corresponding alkyl azides. Copyright Taylor & Francis Inc.

Full text of DOI:10.1080/104265090884292

Phosphorus, Sulfur, and Silicon, 180:1601–1604, 2005
Copyright © Taylor & Francis Inc.
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/104265090884292
Triphenylphosphine/2,3-Dichloro-5,6-
dicyanobenzoquinone in the Presence of n-Bu4NN3 Is a
Useful System for Efficient Conversion of
Tetrahydropyranyl (THP) Ethers to Their Corresponding
Alkyl Azides
Batool Akhlaghinia
Department of Chemistry, Damghan University of Basic Sciences,
Damghan, Iran
Triphenylphosphine/2,3-dichloro-5,6-dicyanobenzoquinone/tetrabutylammonium
azide was used as an efficient system in conversion of tetrahydropyranyl ethers to
corresponding alkyl azides.
Keywords 2,3-dichloro-5,6-dicyanobenzoquinone (DDQ); alkyl azide; azidation; tetrahy-
dro pyranylether (ROTHP); triphenylphosphine (TPP)
INTRODUCTION
Azides1 are versatile functional groups for many purposes in organic
synthesis. Azides have been used extensively in organic synthesis, espe-
cially for the introduction of primary amino groups and the construction
of heterocyclic structures.2 In most cases, aliphatic azides are prepared
by nucleophilic substitution of the corresponding halides or sulfonates
by the azide anion.3
Tetrahydropyranylation is one of the most practical and popular
ways of protecting hydroxyl groups of alcohols and phenols, especially,
in the synthesis of multifunctional organic molecules. THP ethers show
remarkable stability toward some reagents such as organometallic
reagents, hydrides, and reducing and oxidizing agents. Chemical trans-
formation of protected functional groups to other functional groups
is an important step in organic synthesis.4 Literature reveals that
only few reports are available for direct conversion of THP ethers to
Received July 8, 2004; accepted August 2, 2004.
The author acknowledges the partial support of this study by the Damghan University
Research Council.
Address correspondence to Batool Akhlaghinia, Department of Chemistry, Damghan
University of Basic Sciences, Damghan, Iran. E-mail: b akhlaghinia@dubs.ac.ir
1601

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B. Akhlaghinia
other functional groups. The examples are conversion of THP ethers to
bromides,5,6 iodides,7 sulfides,8 acetates,9 and esters.10
In this study, a novel and simple method for efficient conversion of
tetrahydropyranyl ethers to alkyl azides is reported.
RESULTS AND DISCUSSION
Recently, Iranpoor et al.11 have reported the application of
Ph3P/DDQ/R4NX (X = Cl, Br, I, CN, N3) for conversion of alcohols, thi-
ols, and selenols into their corresponding alkyl halides, cyanides, and
azides. Due to wide applicability of tetrahydropyranyl ethers in mul-
tistep synthesis, and in continuation of the study on the conversion
of tetrahydropyranyl ethers to alky cyanides,12 transformation of THP
ethers to alkyl azides by using the Ph3P/DDQ/n-Bu4NN3 system under
neutral and mild reaction conditionwas investigated (Scheme 1).
SCHEME 1
In order to optimize the reaction conditions, at first the effects of
different ratios of ROTHP/PPh3/DDQ/n-Bu4NN3, solvent, and temper-
ature for conversion of PhCH2OTHP to PhCH2N3 were examined. Em-
ploying the ratio of 1/1.5/2/2 in CH3CN at reflux gave the best result
and produced benzyl azide after 19 h in 98% yield. To obtain high iso-
lated yields of alkyl azides, different ratios of Ph3P/DDQ were exam-
ined. The additional amount of Ph3P in the presence of alkyl azides
produces iminiphosphoranes,13 which reduces the isolated yields of
reactions. These optimized conditions were applied for conversion of
structurally different tetrahydropyranyl ethers into their correspond-
ing alkyl azides. The results are shown in Table I. As shown in Table I,
this method is very suitable for the conversion of primary, secondary,
and tertiary tetrahydropyranyl ethers to alkyl azides in excellent
yields.
In conclusion, the present investigation has demonstrated that the
use of Ph3P/DDQ/n-Bu4NN3 offers a simple, novel, and convenient
method for the conversion of a wide variety of tetrahydropyranyl ethers
to their corresponding alkyl azides.

Alkyl Azides
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TABLE I Conversion of Tetrahydropyranyl Ethers into Alkyl
Azides in Dry Acetonitrile under Reflux Condition
Entry
ROTHP
Time (h)
Conversion %a
Isolated yield %
1
2
22
23
100
100
95
90
3
4
23
24
100
100
94
89
5
6
21
21
100
100
97
96
7
8
19
100
100
98
98
18.5
9
20
100
100
93
90
10
21.5
11
21
100
97
aGC yield using internal standard.
EXPERIMENTAL
Chemicals were obtained from Merck and Fluka chemical companies.
FT-IR spectra were recorded on a Perkin Elmer RXI spectrometer.
All tetrahydropyranyl ethers were synthesized as described in the
literature.14 The products were purified by column chromatography and
the purity determination of the products was accomplished by GLC on a
Shimadzu model GC 10-A instrument using n-octane as internal stan-
dard or by thin layer chromatography on silica gel polygram on SIL

1604
B. Akhlaghinia
G/UV 254 plates. NMR spectra were recorded on a Brucker Avance
DPX 250 MHz instrument.
Typical Procedure for Conversion of Benzyl Tetrahydropyranyl
Ether to Benzyl Azide
To a flask containing a mixture of DDQ (2 mmol, 0.454 g) and Ph3P
(1.5 mmol, 0.393) in dry CH3CN (5 mL), while stirring Bu4NN3 (2 mmol,
0.568 g), was added. Benzyl tetrahydropyranyl ether (1 mmol, 0.192 g)
was then added to this mixture. The reaction mixture was refluxed. GC
analysis showed that the reaction was completed after 19 h. The solvent
was evaporated under reduced pressure. Column chromatography of
the crude product on silica-gel using n-hexane as eluent gave benzyl
cyanide in 98% yield. The product was identified by comparison of its
physical constants and spectral data with those of an authentic sample.
REFERENCES
[1] E. F. V. Scriven and K. Turnbull, Chem. Rev. 88, 351 (1988).
[2] T. Sheradsky, In The Chemistry of Azido Groups; S. Patai (Ed.) (Interscience Pub-
lishers, New York, 1971).
[3] a) M. E. C. Biffin, J. Miller, and D. B. Paul, In The Chemistry of Azido Groups, S. Patai
(Ed.) (Interscience, New York, 1971); b) S. G. Alvarez and M. T. Alvarez, Synthesis,
4, 413 (1997).
[4] a) P. J. Kocienski, Protecting Groups, Thieme (Verlag New York, 1994); b) T. W.
Green and P. G. M. Wuts, Protective Groups in Organic Synthesis, 2nd ed. (John
Wiley, New York, 1991); c) A. J. Pearson and N. J. Roush, Handbook of Reagents
for Organic Synthesis Activating Agents and Protecting groups, 1st ed. (John Wiley,
New York 1999).
[5] A. Wagner, M. Heitz, and C. Mioskowski, Tetrahedron Lett., 30, 557 (1989).
[6] A. Tanaka and T. Oritani, Tetrahedron Lett., 38, 1995 (1997).
[7] H. Firouzabadi, N. Iranpoor, and H. Hazarkhani, Tetrahedron Lett., 43, 7139 (2002).
[8] T. Sato, J. Otera, and H. Nozaki, J. Org. Chem., 55, 4770 (1990).
[9] S. Chandrrasekhar, T. Ramachandar, M. V. Reddy, and M. Takhi, J. Org. Chem., 65,
4729 (2000).
[10] S. Kim and W. J. Lee, Synth. Commun., 16, 659 (1986).
[11] a) N. Iranpoor, H. Firouzabadi, G. Aghapour, and A. R. Vaezzadeh, Tetrahedron, 58,
8689 (2002); b) N. Iranpoor, H. Firouzabadi, B. Akhlaghinia, and N. Nowrouzi, J.
Org. Chem., 69, 2562 (2004); c) N. Iranpoor, H. Firouzababi, B. Akhlaghinia, and N.
Nowrouzi, Tetrahedron Lett., 45, 3291 (2004).
[12] B. Akhlaghinia, Phosphors, Sulfur, and Silicon, 179, 1783 (2004).
[13] H. Staudinger and J. Meyer, Helv. Chim. Acta, 2, 635 (1919).
[14] A. Molnar and T. Beregszaszi, Tetrahedron Lett., 37, 8597 (1996).