Convenient and efficient triton b-mediated synthesis of functionalized oxime ethers

Article abstract of DOI:10.1080/00397910802604216

Mild and efficient Triton B-catalyzed Michael addition of oximes to electron-deficient alkenes is described. This convenient methodology allows for the preparation of a variety of functionalized oxime ethers in high yield. Copyright Taylor & Francis Group

Full text of DOI:10.1080/00397910802604216

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Convenient and Efficient
Triton B–Mediated Synthesis of
Functionalized Oxime Ethers
H. M. Meshram a , B. Eeshwaraiah a , M. Sreenivas a
D. Aravind a , B. Syama Sundar b & J. S. Yadav a
,
a Organic Chemistry Division I, Indian Institute of
Chemical Technology , Hyderabad, India
b Department of Chemistry , Acharya Nagarjuna
University , Guntur, India
Published online: 15 Apr 2009.
To cite this article: H. M. Meshram , B. Eeshwaraiah , M. Sreenivas , D. Aravind ,
B. Syama Sundar & J. S. Yadav (2009) Convenient and Efficient Triton B–Mediated
Synthesis of Functionalized Oxime Ethers, Synthetic Communications: An International
Journal for Rapid Communication of Synthetic Organic Chemistry, 39:10, 1857-1863,
DOI: 10.1080/00397910802604216
To link to this article: http://dx.doi.org/10.1080/00397910802604216
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Synthetic Communications1, 39: 1857–1863, 2009
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910802604216
Convenient and Efficient Triton B–Mediated
Synthesis of Functionalized Oxime Ethers
H. M. Meshram,1 B. Eeshwaraiah,1 M. Sreenivas,1 D. Aravind,1
B. Syama Sundar,2 and J. S. Yadav1
1Organic Chemistry Division I, Indian Institute
of Chemical Technology, Hyderabad, India
2Department of Chemistry, Acharya Nagarjuna University,
Guntur, India
Abstract: Mild and efficient Triton B–catalyzed Michael addition of oximes to
electron-deficient alkenes is described. This convenient methodology allows for
the preparation of a variety of functionalized oxime ethers in high yield.
Keywords: Acrylonitrile, methyl acrylate, oxime, oxime ethers, Triton B (quaternary
ammonium hydroxide salt)
Oxime ethers are important in organic synthesis[1] and also in pharma-
ceuticals (I).[2] Steroidal oxime ethers are also known to inhibit
aromatization in breast cancer therapy.[3]
Received September 10, 2008.
Address correspondence to H. M. Meshram, Organic Chemistry Division I,
Indian Institute of Chemical Technology, Hyderabad 500007, India. E-mail:
hmmeshram@yahoo.com
1857

1858
H. M. Meshram et al.
A classical method for installing this functionality is the base-
catalyzed reaction of oximes with alkyl halides.[4] However, such stra-
tegies have the drawback of using lachrymatric halides and corrosive
bases. Recently, oxime ethers have been prepared based on allylic sub-
stitution using palladium as the catalyst.[5] However, varieties of cata-
lysts such as indium(III) bromide,[6] fluorapalite,[7] and indium(III)
chloride[8] are known to perform Michael addition. Although these
methods provide good yields, they have the drawback of using a metal
catalyst, which generates metal-ion-containing waste. Moreover,
tedious workup and harsh reaction conditions also prevent these meth-
ods from general applications in the context of green chemistry, so
there is a need to devise an alternative protocol without metallic base
or catalyst.
TritonB is a nonmetallic organic base. TritonB is known to act as an
additive in organic reactions, such as epoxidation.[9] However, recent
reports reveal the use of TritonB as an efficient and nonmetallic base
for alkynyation,[10] Michael-type addition,[11] nitro aldol condensa-
tion,[12] and carbamate formation.[13] Because of our involvement in the
development of nonmetallic reagents[14] herein we report the results
of Triton B–mediated synthesis of functionalized oxime ethers by
Michael-type addition (Scheme 1).
The Michael addition of cyclohexanone oxime (1 mmol) to methyl
acrylate (1.5 mmol) was examined in the presence of different ratios of
Triton B (1 eq., 1.5 eq., 2 eq., and 3 eq.) at room temperature. Among
these, the use of 1.5 eq. of Triton B was found to be the most effective
to afford cyclohexanone oxime ether (entry d) in 95% yield. The yield
of 1a was decreased when 1 eq. of methyl acrylate was used.
However, the rate of the reaction can be enhanced by the addition of
more equivalents of Triton B. When the reaction of cyclohexanone oxime
and methyl acrylate was performed with 3 eq. of Triton B, the expected
oxime ether 1a was obtained in qualitative yield in 2 h. Under optimized
conditions,[15] various substituted aryl oximes (entries f to n) having
electron donating and electron-withdrawing substituents were found to
give the corresponding oxime ethers in good yield.
Scheme 1.

Synthesis of Functionalized Oxime Ethers
1859
It was noticed that electron-withdrawing substituents enhance the
rate of reaction. Reaction of nitro benzaldoxime (entry l) with methyl
acrylate was accomplished in a very short time (40 min), and thiophine
2-carboaldoxime and pyridine 2-carboaldoxime react smoothly with
methyl acrylate, giving the corresponding oxime ethers in high yield.
Apart from aliphatic and aromatic oximes, hetero aryl oximes
(entries f to j) also underwent a smootheaction leading to the correspond-
ing oxime ether product in high yield.
The efficiency of the procedure was further strengthened by the
successful conversion of camphor oxime (entry o) and cholestananone
oxime (entry q) into the corresponding oxime ethers. From Table 1, it
can be observed that addition of oximes to methyl-ubstituted electron-
deficient alkenes decreases the rate of reaction. For example, Michael
addition of cyclohexanoneoxime (entry e) and pyridine 2-carboxaldoxime
(entry j) to methylmethacrylate requires a longer reaction time for the
completion of the reaction.
The present procedure is compatible with a variety of functional
groups such as ester and nitrile, which give further scope to build more
diverse oxime ethers.
EXPERIMENTAL
General Experimental Procedure
A mixture of oxime (1 mmol), acrylonitrile or methylacrylate (1.5 mmol),
and Triton B (2 ml) were stirred at room temperature for a stipulated time
(see Table 1). The progress of the reaction was monitored by thin-layer
chromatography (TLC). After completion of the reaction, it was
extracted with solvent ether (3 ꢀ 10 ml).
The combined ether extract was washed with water and dried over
anhydrous sodium sulphate, and the solvent was removed under
vacuum. The residue was purified through a small pad of silica gel using
hexane–ethyl acetate (9:1).
Spectral Data for Selected Products
Compound a
Liquid, IR (KBr): t 3415, 2932, 2252, 1740, 1637, 1455, 1376, 1263, 1195,
1
1084, 1056, 885, 602 cmꢁ1; H NMR (300 MHz, CDCl3): d 7.31 (t, 1H,
J ¼ 6.0 Hz), 4.22 (t, 2H, J ¼ 6.0 Hz), 2.62 (t, 2H, J ¼ 6.8 Hz), 2.19–2.11

1860
H. M. Meshram et al.
Table 1.
Time Yield
(min) (%)b
Entry
Oximes
Producta
a
b
45
50
89
87
c
40
50
90
88
d
e
5.0 (h) 77
f
40
45
89
87
g
h
i
30
40
91
89
j
4.0 (h) 77
k
45
90
l
15
50
94
87
m
n
50
86
(Continued )

Synthesis of Functionalized Oxime Ethers
1861
Table 1. Continued
Time Yield
(min) (%)b
Entry
Oximes
Producta
o
45
90
p
q
55
87
40
89
aAll products were characterized by NMR, IR, and mass spectroscopy.
bIsolated yields after purification.
(m, 2H), 1.53–1.43 (m, 2H), 1.36–1.27 (m, 4H), 0.91 (t, 3H, J ¼ 6.798 Hz);
EIMS mass: m=z: 168 Mþ, 155, 141, 129, 103, 82, 75, 57, 43.
Compound d
Liquid. IR (KBr): t 3416, 2935, 2923, 1742, 1639, 1438, 1383, 1257, 1176,
1
1046, 916, 838, 780 cmꢁ1; H NMR (300 MHz, CDCl3): d 4.17 (t, 2H,
J ¼ 6.1 Hz), 3.61 (s, 3H), 2.58 (t, 2H, J ¼ 6.1 Hz), 2.36 (t, 2H, J ¼ 6.9 Hz),
2.12 (t, 2H, J ¼ 6.9 Hz), 1.67–1.50 (m, 6H); EIMS mass: m=z: 199 Mþ,
113, 103, 96, 82, 71, 75, 59, 55, 41.
Compound j
Liquid. IR (KBr): t 3416, 2944, 1737, 1586, 1463, 1378, 1261, 1203, 1046,
950, 777, 516 cmꢁ1; 1H NMR (300 MHz, CDCl3): d 8.57 (d, 1H, J ¼ 5.2 Hz)
8.11 (s, 1H), 7.80 (d, 1H, J ¼ 7.8 Hz), 7.66 (dt, 1H, J ¼ 1.7, 7.8 Hz), 7.26
(dd, 1H, J ¼ 1.7, 5.2 Hz), 4.41, 4.19 (dd, 2H, J ¼ 6.9, 11.3 Hz), 3.70
(s, 3H), 3.02–2.84 (m, 1H), 1.24 (d, 3H, J ¼ 6.9 Hz); EIMS mass: m=z:
222 Mþ, 191, 165, 133, 123, 107, 92, 85, 79, 78, 63, 58, 57, 51, 43.

1862
H. M. Meshram et al.
Compound n
Liquid. IR (KBr): t 3415, 2957, 2840, 1729, 1608, 1513, 1463, 1348, 1305,
1251, 1171, 1058, 1030, 954, 833, 580 cmꢁ1; 1H NMR (300 MHz, CDCl3):
d 7.96 (s, 1H), 7.47 (d, 2H, J ¼ 8.9 Hz), 6.85 (d, 2H, J ¼ 8.9 Hz), 4.38 (t,
2H, J ¼ 6.6 Hz), 3.81 (s, 3H), 3.70 (s, 3H), 2.71 (t, 2H, J ¼ 6.6 Hz); EIMS
mass: m=z: 237 Mþ, 206, 151, 134, 107, 93, 77, 71, 59, 43.
Compound p
Liquid. IR (KBr): t 3413, 2963, 2251, 1667, 1454, 1378, 1275, 1196, 1118,
1
1046, 890, 826, 536 cmꢁ1; H NMR (300 MHz, CDCl3): d 4.23 (t, 2H,
J ¼ 6.1 Hz), 3.7 (s, 3H), 2.6 (t, 2H, J ¼ 6.1 Hz), 2.44 (m, 1H), 1.90–1.80
(m, 2H), 1.76–1.31 (m, 4H), 0.97 (s, 3H), 0.90 (s, 3H), 0.78 (s, 3H); EIMS
mass: m=z: 220 Mþ, 190, 175, 150, 147, 134, 122, 108, 94, 81, 69, 55, 41.
ACKNOWLEDGMENTS
The authors are thankful to the Council of Scientific and Industrial
Research, New Delhi, for the award of a fellowship.
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