Direct conversion of tosylhydrazones to tert-butyl ethers under Bamford-Stevens reaction conditions

Article abstract of DOI:10.1055/s-2001-18083

A new method for the preparation of tert-butyl ethers is described starting from aryl aldehyde and ketone tosylhydrazones under Bamford-Stevens reaction conditions (t-BuOK/t-BuOH).

Full text of DOI:10.1055/s-2001-18083

LETTER
1779
Direct Conversion of Tosylhydrazones to tert-Butyl Ethers under Bamford-
Stevens Reaction Conditions1
D
irec
t
Conver
.
sion of Tosy
C
lhydrazones to te
h
rt-Butyl Eth
a
s
ndrasekhar,* G. Rajaiah, L. Chandraiah, D. Narsimha Swamy
Indian Institute of Chemical Technology, Hyderabad 500 007, India
E-mail: srivaric@iict.ap.nic.in
Received 31 July 2001
Table Direct Conversion of Tosylhydrazones to tert-Butyl Ethers
Abstract: A new method for the preparation of tert-butyl ethers is
described starting from aryl aldehyde and ketone tosylhydrazones
under Bamford-Stevens reaction conditions (t-BuOK/ t-BuOH).
Entry Substrate
1
Productb
Yieldsa
(%)
Key words: tosylhydrazones, tert-butyl ethers, potassium tert-
butoxide, tert-butanol, diazocompounds
82
O-tBu
N-NHTs
N-NHTs
N-NHTs
N-NHTs
N-NHTs
S
S
2
85
86
85
O-tBu
Introduction of tert-butyl ether functionality into existing
organic molecule tends to change not only the physical
but also chemical and biological properties of the parent
molecule. For example the alkyl tert-butyl ethers are con-
sidered as possible gasoline additives due to their high en-
ergy content and high octane number.2 Also the bulk of
tert-butyl group efficiently impedes any chelation of the
metal by the oxygen of tert-butyl ether functionality. Oc-
casional reports also show that the tert-butyl functionality
has profound effect on biological profile as exemplified
by several bioactive molecules in SAR studies.3
Me
Me
3
O-tBu
MeO
MeO
MeO
4
5
MeO
BnO
O-tBu
O-tBu
O-tBu
BnO
78
O2N
O2N
6
7
8
9
80
79
76
78
O
O
O
O
N-NHTs
As part of ongoing project on the exploitation of aldehyde
tosylhydrazone chemistry,4 especially the thiophene 2-al-
dehyde tosylhydrazone,4e we have serendipitously ob-
served the formation of tert-butyl ether (Scheme 1) when
the thiophene 2-aldehyde tosylhydrazone was treated with
t-BuOK in t-BuOH (analogous to Bamford-Stevens
reaction5 conditions).
O-tBu
OBn
N-NHTs
OBn
O-tBu
OH
N-NHTs
OH
MeO
MeO
O-tBu
N-NHTs
t-BuOK, tert-BuOH
HO
HO
HO
HO
O-tBu
Ar
N-NHTs
Ar
10
11
12
74
81
79
reflux
O-tBu
N-NHTs
N-NHTs
Ar = heterocycle, substituted phenyl
O-tBu
Scheme 1
This result prompted us to look into the reaction pathway
and also generalize the protocol. The results pertaining to
this new observation are documented herein (Table).
There are some protocols, which describe the synthesis of
tert-butyl ethers6 and few involving photolysis.7
O-tBu
N-NHTs
13
83
N-NHTs
O-tBu
O
O
Mechanistically it is anticipated that, in the presence of
protic solvent, the formed diazo intermediate8 abstracts a
proton to give the diazonium ion, which loses N2 to give
the corresponding carbocation (Bamford-Stevens mecha-
a Yields were calculated after purification by column chromato-
graphy.
b All the products were characterized by 1H NMR, IR and mass
spectroscopy.
Synlett 2001, No. 11, 26 10 2001. Article Identifier:
1437-2096,E;2001,0,11,1779,1780,ftx,en;D17901ST.pdf.
© Georg Thieme Verlag Stuttgart · New York
ISSN 0936-5214

1780
S. Chandrasekhar et al.
LETTER
H
tert-BuOH
-N2
t-BuOK
O-tBu
N-NHTs
N
N
N
N
reflux
tert-BuOH
R
R
R
R
R = alkyl, o-alkyl, hydroxy
Scheme 2
nism) which may not undergo elimination due to the ab-
sence of -hydrogen and hence leading to desired tert-
butyl ether in the presence of t-BuOH (Scheme 2).
Acknowledgement
Two of us (GR and LC) thank CSIR, New Delhi for financial
support.
To further strengthen the above hypothesis, p-tolualde-
hyde tosylhydrazone (entry 2) was treated under similar
reaction conditions to isolate 4-methyl benzyl tert-butyl
ether in 85% yield. Similar results were observed for p-
methoxy benzaldehyde tosylhydrazone (entry 3), 4-ben-
zyloxy-3-methoxy benzaldehyde tosylhydrazone (entry
4), naphthaldehyde tosylhydrazone (entry 11) and fur-
furaldehyde tosylhydrazone (entry 12). Also methylene-
dioxy derivative (entry 6) and o-benzyloxy substrate (
entry 7) yielded the targeted tert-butyl ethers in 80% and
85% yields respectively. The salcilaldehyde tosylhydra-
zone (entry 8) yielded the o-hydroxy benzyl tert-butyl
ether (78% yield). Thus this example demonstrates that
one would prepare the tert-butyl ether of benzyl alcohol in
presence of phenolic functionality without protection.
This result is further demonstrated by the preparation of 3-
hydroxy-4-methoxy benzyl tert-butyl ether (entry 9) and
3-hydroxy benzyl tert-butyl ether (entry 10). Entry 12
demonstrates the formation of very hindered 1,1-diphenyl
methyl tert-butyl ether in 76% yield. p-Nitro benzalde-
hyde tosylhydrazone (entry 5) resulted in the correspond-
ing tert-butyl ether in 78% yield.
References
(1) IICT Communication No. 4825.
(2) (a) Dumont, R.; Guibet, J. C.; Portas, J. Y. Le Methanol;
Masson: Paris, 1984. (b) Jenner, G. Tetrahedron Lett. 1988,
29, 2445.
(3) (a) Bowden, S. K.; Green, P. N. J. Chem. Soc. Part II. 1954,
1795. (b) Micheli, R. A.; Hajos, Z. G.; Cohen, N.; Parrish, D.
R.; Portland, L. A.; Sciamanna, W.; Scott, M. A.; Wehrli, P.
A. J. Org. Chem. 1975, 40, 675. (c) Dictionary of Drug
Indexes; Chapman and Hall.: London,New York, 1990.
(4) (a) Chandrasekhar, S.; Reddy, M. V.; Takhi, M. Tetrahedron
Lett. 1998, 39, 6535. (b) Chandrasekhar, S.; Takhi, M.;
Yadav, J. S. Tetrahedron Lett. 1995, 36, 307.
(c) Chandrasekhar, S.; Takhi, M.; Yadav, J. S. Tetrahedron
Lett. 1995, 36, 5071. (d) Chandrasekhar, S.; Mohapatra, S.;
Takhi, M. Synlett. 1996, 759. (e) Chandrasekhar, S.; Reddy,
M. V.; Reddy, K. S.; Ramarao, C. Tetrahedron Lett. 2000,
41, 2667. (f) Chandrasekhar, S.; Reddy, M. V.; Rajaiah, G.
Tetrahedron Lett. 2000, 41, 10131.
(5) Bamford, W. R.; Stevens, T. S. J. Chem. Soc. 1952, 4735.
(6) (a) Lawesson, S. O.; Yang, N. C. J. Am. Chem. Soc. 1959,
4230. (b) Kropp, P. J.; Adkins, R. L. J. Am. Chem. Soc.
1991, 113, 2709. (c) Alexakis, A.; Gardette, M.; Colin, S.
Tetrahedron Lett. 1988, 29, 2951. (d) Alexakis, A.;
Duffault, J. M. Tetrahedron Lett. 1988, 29, 6243.
(7) (a) Kirmse, W.; Kund, K. J. Am. Chem. Soc. 1989, 111,
1465. (b) Kirmse, W.; Kund, K. J. Org. Chem. 1990, 55,
2325.
(8) (a) Newman, M. S.; Beal, P. F. III J. Am. Chem. Soc. 1950,
5161. (b) Landais, Y.; Planchenault, D. Synlett. 1995, 1191.
(c) Liotta, L. J.; Ganem, B. Tetrahedron Lett. 1989, 30,
4759. (d) Aller, E.; Brown, D. S.; Cox, D. G.; Miller, D. J.;
Moody, C. J. J. Org. Chem. 1995, 60, 4449.
(9) For free hydroxy aldehyde tosylhydrazones (entries 8–10),
t-KOBu (2.4 mmol)was used. After completion, the reaction
mixture was acidified with saturated sodium bisulfate.
(10) Spectral data of products: 1- 1H NMR (200 MHz, CDCl3)
7.22 (m, 1 H), 6.94 (m, 2 H), 4.58 (s, 2 H), 1.22 (s, 9 H). IR
(KBr): 2982, 1574, 1054 cm-1. EI MS m/z; 170 (M+), 114, 97.
6- 1H NMR (200 MHz, CDCl3) 6.82 (s, 1 H), 6.70 (m, 2 H),
5.90 (s, 2 H), 4.32 (s, 2 H), 1.26 (s, 9 H). IR (KBr): 2972,
1568, 1020 cm-1. EIMS m/z; 208 (M+), 152, 135. 12- 1H
NMR (200 MHz, CDCl3) 7.20 (m, 10 H), 5.51 (s, 1 H),
1.21 (s, 9 H). IR (KBr): 2986, 1590, 1048 cm-1. EIMS m/z;
240 (M+), 184, 167, 107.
In conclusion, it is demonstrated that aryl aldehydes and
ketones can be converted to corresponding tert-butyl
ethers via tosylhydrazones. Further studies to modify the
present protocol and its applications are being pursued ac-
tively.
General Procedure
To the stirred solution of potassium tert-butoxide (1.2 mmol)9 in t-
BuOH was added arylaldehyde tosylhydrazone (1 mmol) at 0 °C
and allowed to stir for 10 minutes. The reaction mixture was re-
fluxed for 4 hours and cooled to room temperature. t-BuOH was re-
moved under vacuum and residue was extracted with ethylacetate (3
20 mL), washed with water, brine and dried over sodium sulfate
and purified by column chromatography to afford the pure prod-
uct.10
Synlett 2001, No. 11, 1779–1780 ISSN 0936-5214 © Thieme Stuttgart · New York