An efficient one-pot synthesis of oxime ethers from alcohols using triphenylphosphine/carbon tetrachloride

Article abstract of DOI:10.1055/s-0029-1218711

A convenient and efficient one-pot O-alkylation of oximes from alcohols using triphenylphosphine in carbon tetrachloride is described. In this method, treatment of alcohols with a mixture of triphenylphosphine, carbon tetrachloride, oxime, and DBU in the presence of catalytic amounts of tetrabutylammonium iodide in refluxing acetonitrile regioselectively furnishes the corresponding O-alkyl ethers in good yields. This methodology is highly efficient O-alkylation of oximes with various structurally diverse alcohols. Semiempirical quantum-mechanic calculations (AM1) for unsymmetrical oxime ethers, indicated a lower heat of formation for Z-isomers. Georg Thieme Verlag Stuttgart - New York.

Full text of DOI:10.1055/s-0029-1218711

1724
PAPER
An Efficient One-Pot Synthesis of Oxime Ethers from Alcohols Using
Triphenylphosphine/Carbon Tetrachloride
One-PotSynthesisof
O
o
xime
E
thershammad Navid Soltani Rad,*a Ali Khalafi-Nezhad,*b Fatemeh Karimitabar,b Somayeh Behrouza
a
Department of Chemistry, Faculty of Basic Sciences, Shiraz University of Technology, Shiraz 71555-313, Iran
Fax +98(711)7354523; E-mail: soltani@sutech.ac.ir; E-mail: nsoltanirad@gmail.com
b
Department of Chemistry, College of Sciences, Shiraz University, Shiraz 71454, Iran
Received 8 February 2010; revised 17 February 2010
oximes with alcohols which mostly are based on Mitsuno-
bu conditions.17 However, the use of diethyl azodicarbox-
ylate restricts the applicability of this method, since it is
an explosive, expensive, toxic, thermally unstable, shock-
Abstract: A convenient and efficient one-pot O-alkylation of
oximes from alcohols using triphenylphosphine in carbon tetrachlo-
ride is described. In this method, treatment of alcohols with a mix-
ture of triphenylphosphine, carbon tetrachloride, oxime, and DBU
in the presence of catalytic amounts of tetrabutylammonium iodide sensitive, and photosensitive reagent.
in refluxing acetonitrile regioselectively furnishes the correspond-
The use of the well-known combination of tertiary phos-
ing O-alkyl ethers in good yields. This methodology is highly effi-
cient O-alkylation of oximes with various structurally diverse
alcohols. Semiempirical quantum-mechanic calculations (AM1) for
unsymmetrical oxime ethers, indicated a lower heat of formation for
Z-isomers.
phines with tetrahalomethanes has found increasing appli-
cation in preparative chemistry for halogenations,
dehydrations, and P–N linking reactions.18 Among these
combinations, triphenylphosphine in carbon tetrachloride
is a famous reagent that can convert an alcohol into the
corresponding alkyl halide19 under mild conditions.
Moreover, the triphenylphosphine in carbon tetrachloride
system has various important applications including: con-
version of alcohols into nitriles20 and esters,21 chlorination
and chlorodehydration of 1,2-diols,22 cyclodehydration of
chiral diols,23 dehydration of aldoximes24a and amides,24b
conversion of carboxylic acids into amides25a and acid
chlorides,25b and synthesis of benzoxazoles,26a 1,3,4-oxa-
diazoles,26b b-lactams,26c and N-acylindolines.26d
Key words: oxime, alcohol, O-alkylation, triphenylphosphine, car-
bon tetrachloride, DBU
Oximes and oxime ether derivatives are important sub-
strates in organic and medicinal chemistry.1 Oximes and
oxime ethers are widely used for the introduction of vari-
ous functional groups into organic compounds,1a,d,e as
well as for amino acid synthesis.2 Moreover, they are a
key structural motif in many drug scaffolds and bioactive
compounds. Many famous drugs with various types of
chemotherapeutic activity, such as antiviral (e.g., en-
viroxime)3 and anti-inflammatory agents (e.g., pi-
foxime),1b cephalosporin antibiotics (e.g., cefixime),4
nerve agent antidotes (e.g., pralidoxime),1b,c antifungal
agents (e.g., oxiconazole),5 macrolide antibiotics (e.g.,
roxithromycin),6 antidepressants (e.g., fluvoxamine),1b
and thromboxane synthase inhibitors (e.g., ridogrel),7
contain an oxime or oxime ether moiety in their structure.
Encouraged by the significance role of oxime ethers in
medicinal chemistry and also in continuation of our inter-
ests in use of triphenylphosphine and carbon tetrachloride
for organic transformations,27 herein, we described the
preparation of compounds 1a–p via O-alkylation of
oximes with alcohols using triphenylphosphine and car-
bon tetrachloride in the presence of 1,8-diazabicyc-
lo[5.4.0]undec-7-ene and catalytic amounts of
tetrabutylammonium iodide in anhydrous acetonitrile
(Scheme 1).
One of the most common routes to oxime ethers is the re-
action of oximes with carbon electrophiles, including
alkyl or aryl halides,8,9 aryl nitrates,10a arenediazonium
salts,10b epoxides,1a,11 activated olefins,12 trialkyl orthofor-
mates,13 allylic carbonates,14a acetates,14a,b phosphate es-
ters,14c and Michael acceptors.15 Oxime ethers have also
been prepared from the condensation of O-alkylhydroxyl-
amines with carbonyl compounds.16 In view of the wide
diversity and availability of alcohols and their lower tox-
icity and ease of handling with respect to alkyl halides, the
one-pot reaction of oximes with alcohols seems to be a
suitable and attractive strategy. Indeed, there are a few re-
ports that have exemplified the one-pot O-alkylation of
O
R3
OH
N
N
Ph3P, CCl4, DBU
R3OH
+
R1
R2
R1
R2
MeCN, TBAI, Δ, 6-10 h
1a–p
R1, R2 = alkyl, aryl
R3 = alkyl, benzyl, allyl
48–78%
Scheme 1 Preparation of oxime O-alkyl ethers from alcohols using
triphenylphosphine and carbon tetrachloride
The first step of this synthetic approach was to find the op-
timized reaction conditions. The optimization began by
studying the effect of various solvents on the model reac-
tion of 9H-fluoren-9-one oxime, allyl alcohol, and DBU
in the presence of a mixture of triphenylphosphine in car-
bon tetrachloride and a catalytic amount of tetrabutylam-
monium iodide (Table 1).
SYNTHESIS 2010, No. 10, pp 1724–1730
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x.
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x
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Advanced online publication: 24.03.2010
DOI: 10.1055/s-0029-1218711; Art ID: Z02510SS
© Georg Thieme Verlag Stuttgart · New York

PAPER
One-Pot Synthesis of Oxime Ethers
1725
As the data in Table 1 indicates, anhydrous acetonitrile
(entry 4) was the most appropriate solvent and was used
for all further reactions. In view of the fact that the gener-
ated reactive intermediates in the reaction mixture are
very susceptible to moisture, the use of a well-dried sol-
vent is essential and highly recommended. The explicit in-
terference of moisture was easily observed by comparing
the obtained results in hydrous and anhydrous acetonitrile
(entries 3 and 4). Using dimethyl sulfoxide and N,N-di-
methylformamide afforded a moderate yield of the corre-
sponding 9H-fluoren-9-one O-allyloxime (1h) (entries 6
and 7). Other solvents were inefficient even if the reaction
time was prolonged (72 h).
Table 2 Effect of Various Bases on the Conversion of 9H-Fluoren-
9-one Oxime into 9H-Fluoren-9-one O-Allyloxime (1h) in Anhyd-
rous Acetonitrile
OH
O
N
N
Ph3P
CCl4
base
HO
+
MeCN
TBAI, Δ
1h
Entry
Base
none
Time (h)
Yielda (%)
b
1
2
3
4
5
6
7
8
9
72
12
6
–
DBN
DBU
35
Table 1 Effect of Various Solvents on the Conversion of 9H-Fluo-
ren-9-one Oxime into 9H-Fluoren-9-one O-Allyloxime (1h)
75
DABCO
DMAP
MgO
24
24
72
8
trace
trace
–
OH
O
N
N
Ph3P
CCl4
DBU
HO
+
solvent
TBAI
Δ
1h
Cs2CO3
K2CO3
Et3N
42
Entry
Solventa
CCl4
Time (h)
Yieldb (%)
12
12
38
1
2
3
4
5
6
7
8
9
12
18
72
6
20
15
25
a Isolated yield.
THF
b No reaction after 72 h at reflux.
c
MeCN
MeCN
HMPA
DMSO
DMF
–
tetrabutylammonium iodide provided 1h in higher yields
and with a shorter reaction time. Other phase-transfer cat-
alysts were not as effective as tetrabutylammonium io-
dide.
75
25
32
35
12
10
10
72
72
In other experiments, we investigated the influence of
several reagents as sources for positive-halogen in combi-
nation with triphenylphosphine instead of carbon tetra-
chloride. As shown by the results in Table 3, the
triphenylphosphine and carbon tetrachloride system was
found to be the most suitable and efficient reagent for the
conversion of allyl alcohol into 1h. Using N-chlorosuccin-
imide, N-bromosuccinimide, isocyanuric chloride, and
bromine (entries 2–5) did not afford satisfactory results.
2,3-Dichloro-5,6-dicyano-1,4-benzoquinone and tri-
iodomethane (entries 6 and 7) were inefficient even after
72 hours at reflux.
c
toluene
acetone
–
c
–
a All solvents were anhydrous, with the exception of MeCN (entry 3).
b Isolated yield.
c No reaction after 72 h at reflux.
The choice of the base for the activation of the O–H bond
in the oxime for reaction with alkoxyphosphonium salt in-
termediates is of great significance. In this case, we eval-
uated the effect of various organic and inorganic bases on
the model reaction (Table 2). In the absence of base, no re-
action took place even after prolonged reaction times (72
h). DBU (entry 3) proved to be the most efficient base for
conversion of 9H-fluoren-9-one oxime into 9H-fluoren-9-
one O-allyloxime (1h) (entry 3). Some bases, such as
DBN, Cs2CO3, and K2CO3 (Table 2, entries 2, 7, and 8),
afforded lower yields of 1h, while other bases were far
less efficient.
The optimized stoichiometric ratio of Ph3P/CCl4/ROH/
oxime/DBU for the conversion of allyl alcohol into 1h
was found to be 1.5:2:1.5:1:1.
To evaluate the generality and versatility of this method,
the optimized conditions were employed with various
structurally diverse primary, secondary, tertiary, allylic,
and benzylic alcohols as well as symmetric and unsym-
metrical oximes. The data in Table 4 indicates that the
method is suitable and efficient for various alcohols in-
cluding: primary and secondary alcohols, while tertiary
alcohols did not give satisfactory results. For example, O-
alkylation of benzophenone oxime with tert-butyl alcohol
did not afford the corresponding product 1e. The general-
ity of the method was confirmed with respect to allylic 1b,
We also investigated the role of various phase-transfer
catalysts on the model reaction. In this case, tetrabutylam-
monium halides (TBAX, X = F, Cl, Br, I) were employed.
In the absence of the phase-transfer catalyst, the reaction
occurred but only in low yields (<50%). However, using
Synthesis 2010, No. 10, 1724–1730 © Thieme Stuttgart · New York

1726
M. N. Soltani Rad et al.
PAPER
Table 4 One-Pot O-Alkylation of Oximes via Alcohols Using Ph3P,
CCl4, DBU and TBAI in Refluxing Acetonitrile
Table 3 Effect of Various Reagents on Conversion of 9H-Fluoren-
9-one Oxime into 9H-Fluoren-9-one O-Allyloxime (1h)
Entry Compd Structurea
Time Yieldb
OH
O
N
N
(h)
(%)
reagent, DBU
HO
+
O
O
N
MeCN, TBAI, Δ
1
2
1a
1b
6
72
1h
Entry
Reagent
Time (h) Yielda (%)
N
1
2
3
4
5
6
7
Ph3P, CCl4
6
12
12
24
24
72
72
75
25
34
21
14
10
12
6
7
74
68
Ph3P, NCS
Ph3P, NBS
Ph3P, isocyanuric chloride
Ph3P, Br2
O
O
N
N
O
3
4
5
1c
Ph3P, DDQ
Ph3P, CHI3
a Isolated yield.
1d17
9
52
1h, and 1m, benzylic 1l and 1p, aliphatic 1d, 1g, 1j, and
1k, and other alcohols containing N-heterocycles 1i and
1n. Moreover, this method is applicable for all symmetri-
cal and unsymmetrical oximes including aliphatic and ar-
omatic residues. Most of the oximes used in this research
were commercially available or could be easily prepared
using the procedure reported in the literature.28 The un-
symmetrical oximes were used as mixtures of their E- and
Z-isomers.
O
O
c
N
N
1e
72
–
6
7
8
1f
7
6
6
71
70
75
The selectivity of this method was demonstrated via a
competitive reaction of a mixture consisting of 2-phenyl-
ethanol, i-PrOH, Ph3P, CCl4, benzophenone oxime and
DBU in the molar ratio of (1.5:1.5:1.5:2:1:1) under the op-
timized conditions. The results in Table 5 demonstrate the
selectivity between primary and secondary alcohols.
There was high selectivity for the O-alkylation of oximes
using the primary alcohol rather than the secondary ana-
logue (entry 1). The same result was observed when a
mixture of butanol and isopropyl alcohol was investigated
in the O-alkylation of 9H-fluoren-9-one oxime (entry 2).
O
O
N
N
1g
1h
Oximes are known to be ambident nucleophiles.29 The
alkylation of an oxime can be achieved at the oxygen to
afford an O-alkyl ether or at the nitrogen to generate a ni-
trone.30 Like other ambident systems, the site of alkylation
in the oxime anion is affected by a number of factors, such
as the base and the solvent types, the nature of the alkylat-
ing agents and the cation, the geometry of the substrate,
functional groups present on the oxime, and the degree of
dissociation of the oxime salts.30,31 However, using the
present method, O-alkyl ethers were mainly obtained and
nitrones were not detected, even in trace amounts.
N
N
O
O
O
N
N
9
1i
1j
10
48
56
10
8
Synthesis 2010, No. 10, 1724–1730 © Thieme Stuttgart · New York

PAPER
One-Pot Synthesis of Oxime Ethers
1727
Table 4 One-Pot O-Alkylation of Oximes via Alcohols Using Ph3P,
CCl4, DBU and TBAI in Refluxing Acetonitrile (continued)
All compounds were fully characterized, and their struc-
tures were confirmed by IR, 1H and 13C NMR, MS, and el-
emental analysis. Compounds 1k–n were expected to be
produced as two geometrical isomers (E- or Z-isomers);
however, Z-isomers were obtained predominantly as
shown by 1H and 13C NMR analysis; the minor E-isomer
was also detected in trace amounts (<5%). To rationalize
this fact, AM1 semiempirical quantum mechanic calcula-
tion was applied using MOPAC in CS Chem 3D Ultra 8
(Cambridge Soft, 2004) or Hyperchem (Hypercube Inc.,
Version 7). The results are summarized in Table 6, in
which DE refers to the discrepancy of energy between the
Z- and E-isomers [DE = EZ – EE (kcal/mol)]. As can be
seen, all DE values calculated for oxime ethers 1k–n have
a negative value. There is conformity to the experimental
observations and calculated data (Table 6) which endorse
the higher stability of Z-isomers in comparison with E-
isomers, and, hence, the predominant formation of Z-
products.
Entry Compd Structurea
Time Yieldb
(h)
(%)
O
N
11
12
1k8g,h
6
73
O
O
1l8g,h
7
6
78
78
N
N
13
1m
O2N
N
Table 6 Calculated Heat of Formation of Synthesized Unsymmetri-
cal Oxime Ethers 1k–n Using AM1
NO2
N
a
b
Compound EE
EZ
DEc
O
14
15
1n
1o
7
8
73
69
N
MeO
MeO
1k
1l
24.99990
60.62718
53.26502
–11.84439
23.13776
57.73976
51.05852
–12.53704
–1.86214
–2.88742
–2.2065
–0.69265
1m
1n
O
N
O
O
a Heat of formation of the E-isomer (kcal/mol).
b Heat of formation of the Z-isomer (kcal/mol).
c DE = EZ – EE (kcal/mol).
N
16
1p
6
76
In summary, a convenient and efficient synthetic method-
ology for the preparation of some novel oxime ethers via
the O-alkylation of oximes using alcohols in the presence
of triphenylphosphine, carbon tetrachloride, 1,8-diazabi-
cyclo[5.4.0]undec-7-ene, and tetrabutylammonium iodide
(cat.) in refluxing acetonitrile has been established. In this
method various primary, secondary allylic, and benzylic
alcohols underwent reaction with oximes to afford the
corresponding O-alkyl ethers in good yields.
a All products were characterized by IR, 1H and 13C NMR, MS, and
CHN analysis.
b Isolated yield.
c No reaction after 72 h at reflux.
Table 5 Competitive O-Alkylation of Oximes with Primary/
Secondary Alcohols Using Ph3P and CCl4
All chemicals, except oximes, were purchased from either Fluka or
Merck. The oximes were prepared by established methods. Solvents
were purified and dried by standard procedures, and stored over 3Å
molecular sieves. Reactions were followed by TLC using SILG/UV
254 silica gel plates. Column chromatography was performed on
silica gel 60 (0.063–0.200 mm, 70–230 mesh; ASTM). Melting
points were obtained using a Büchi-510 apparatus in open capillar-
ies and are uncorrected. IR spectra were obtained using a Shimadzu
FT-IR-8300 spectrophotometer. 1H and 13C NMR spectra were ob-
tained using a Bruker Avance-DPX-250 spectrometer operating at
250/62.5 MHz, respectively. GC/MS were performed on a Shimad-
zu GC/MS-QP 1000-EX apparatus. Elemental analyses were per-
formed on a Perkin-Elmer 240-B microanalyzer. Full analytical
data are provided for novel products and references are given for
known compounds (see Table 4).
Entry Alcohol mixture Oxime
Compd Time Yielda
(h)
(%)
Ph
NOH
NOH
OH
1a
1d
70
4
1
6
OH
OH
1g
1j
68
3
2
6
OH
a Isolated yield.
Synthesis 2010, No. 10, 1724–1730 © Thieme Stuttgart · New York

1728
M. N. Soltani Rad et al.
PAPER
Oximes; General Procedure28
128.97, 129.09, 129.28, 129.46, 133.20, 134.57, 136.51, 156.88,
157.70.
MS (EI): m/z (%) = 367 (37) [M+].
In a round-bottomed flask (100 mL) a mixture of the ketone (0.01
mol), NH2OH·HCl (1.03 g, 0.015 mol), NaOH (0.6 g, 0.015 mol),
and H2O (minimum amount for solvation of NH2OH·HCl and
NaOH) was dissolved in EtOH (20 mL) and then the soln was
stirred at r.t. for 24 h. The mixture was poured into ice/H2O (20 g:10
g). An oxime precipitate immediately formed that was filtered and
washed with cold H2O and dried. Recrystallization (hot MeOH–
H2O) afforded pure oximes which were used in the next step.
Anal. Calcd for C25H21NO2: C, 81.72; H, 5.76; N, 3.81. Found: C,
81.67; H, 5.79; N, 3.86.
9H-Fluoren-9-one O-Phenethyloxime (1f)
Column chromatography (silica gel, EtOAc–n-hexane, 1:20) af-
forded 1f (2.12 g, 71%) as a pale-yellow solid; mp 71.0 °C; Rf = 0.40
(EtOAc–n-hexane, 1:5).
IR (KBr): 3050, 2961, 2843, 1654, 1471 cm–1.
One-Pot O-Alkylation of Oximes Using Alcohols; General Pro-
cedure
To a two-necked round-bottom flask (100 mL) equipped with a con-
denser was added a mixture of PPh3 (0.015 mol), CCl4 (0.02 mol),
alcohol (0.015 mol), ketoxime (0.01 mol), DBU (0.01 mol), and a
catalytic amount of TBAI (0.1 g) in anhyd MeCN (30 mL). The
mixture was refluxed for the appropriate time until TLC monitoring
indicated no further improvement in the conversion (Table 4). The
solvent was evaporated under vacuum and the remaining foam was
dissolved in CHCl3 (100 mL) and subsequently washed with H2O
(2 × 100 mL). The organic layer was dried (Na2SO4), filtered, and
evaporated. The crude product was purified by column chromatog-
raphy (silica gel).
1H NMR (250 MHz, CDCl3): d = 3.36 (t, J = 6.9 Hz, 2 H, PhCH2),
4.83 (t, J = 6.9 Hz, 2 H, CH2ON), 7.45–7.58 (m, 9 H, aryl), 7.72–
7.77 (m, 2 H, aryl), 8.05–8.08 (m, 1 H, aryl), 8.42–8.45 (m, 1 H,
aryl).
13C NMR (62.5 MHz, CDCl3): d = 36.15, 76.62, 120.14, 121.88,
126.63, 126.97, 128.08, 128.34, 128.75, 129.34, 129.56, 130.02,
130.80, 131.06, 135.89, 138.74, 140.46, 141.52, 152.55.
MS (EI): m/z (%) = 299 (19) [M+].
Anal. Calcd for C21H17NO: C, 84.25; H, 5.72; N, 4.68. Found: C,
84.32; H, 5.75; N, 4.60.
Benzophenone O-Phenethyloxime (1a)
9H-Fluoren-9-one O-Butyloxime (1g)
Column chromatography (silica gel, EtOAc–n-hexane, 1:20) af-
forded 1a (2.16 g, 72%) as a pale-yellow oil; Rf = 0.43 (EtOAc–
n-hexane, 1:5).
IR (liquid film): 3057, 2967, 28.39, 1658, 1476 cm–1.
1H NMR (250 MHz, CDCl3): d = 3.00 (t, J = 7.0 Hz, 2 H, PhCH2),
4.37 (t, J = 7.0 Hz, 2 H, CH2ON), 7.21–7.50 (complex, 15 H, aryl).
13C NMR (62.5 MHz, CDCl3): d = 36.35, 75.59, 126.70, 128.50,
128.75, 128.84, 129.15, 129.66, 129.72, 130.49, 132.74, 134.00,
137.14, 139.19, 157.07.
Column chromatography (silica gel, EtOAc–n-hexane, 1:20) af-
forded 1g (1.75 g, 70%) as a pale-yellow oil; Rf = 0.42 (EtOAc–
n-hexane, 1:5).
IR (liquid film): 3074, 2969, 2840, 1661, 1452 cm–1.
1H NMR (250 MHz, CDCl3): d = 0.86 (t, J = 7.3 Hz, 3 H, Me),
1.37–1.46 (m, 2 H, CH2Me), 1.70–1.79 (m, 2 H, CH2CH2Me), 4.28
(t, J = 6.5 Hz, 2 H, CH2ON), 7.15–7.29 (m, 4 H, aryl), 7.46–7.50 (m,
2 H, aryl), 7.65–7.67 (m, 1 H, aryl), 8.17–8.20 (m, 1 H, aryl).
13C NMR (62.5 MHz, CDCl3): d = 13.99, 19.33, 31.41, 75.75,
119.71, 119.77, 119.82, 121.52, 127.79, 128.13, 129.08, 129.61,
130.70, 135.74, 140.12, 141.24, 151.83.
MS (EI): m/z (%) = 301 (35) [M+].
Anal. Calcd for C21H19NO: C, 83.69; H, 6.35; N, 4.65. Found: C,
83.64; H, 6.37; N, 4.71.
MS (EI): m/z (%) = 251 (45) [M+].
Anal. Calcd for C17H17NO: C, 81.24; H, 6.82; N, 5.57. Found: C,
81.32; H, 6.89; N, 5.62.
Benzophenone O-Allyloxime (1b)
Column chromatography (silica gel, EtOAc–n-hexane, 1:20) af-
forded 1b (1.75 g, 74%) as a colorless oil; Rf = 0.75 (EtOAc–n-hex-
ane, 1:5).
IR (liquid film): 3056, 2937, 2854, 1658, 1449 cm–1.
1H NMR (250 MHz, CDCl3): d = 5.03–5.05 (m, 2 H, CH2ON),
5.46–5.64 (m, 2 H, =CH2), 6.28–6.44 (m, 1 H, =CH), 7.56–7.70 (m,
10 H, aryl).
13C NMR (62.5 MHz, CDCl3): d = 75.64, 117.50, 128.22, 128.38,
128.53, 128.78, 129.02, 129.55, 133.76, 134.82, 136.87, 157.01.
MS (EI): m/z (%) = 237 (42) [M+].
9H-Fluoren-9-one O-Allyloxime (1h)
Column chromatography (silica gel, EtOAc–n-hexane, 1:20) af-
forded 1h (1.76 g, 75%) as a yellow foam; Rf = 0.72 (EtOAc–n-hex-
ane, 1:5).
IR (liquid film): 3053, 2937, 2856, 1654, 1449 cm–1.
1H NMR (250 MHz, CDCl3): d = 4.97–5.00 (m, 2 H, CH2ON),
5.32–5.55 (complex, 2 H, =CH2), 6.13–6.32 (m, 1 H, =CH), 7.31–
7.45 (m, 4 H, aryl), 7.61–7.64 (m, 2 H, aryl), 7.83–7.84 (m, 1 H,
aryl), 8.37–8.40 (m, 1 H, aryl).
13C NMR (62.5 MHz, CDCl3): d = 76.71, 118.04, 119.86, 119.91,
121.19, 127.89, 128.22, 129.37, 129.85, 130.64, 130.93, 134.02,
135.65, 140.27, 141.38, 152.41.
Anal. Calcd for C16H15NO: C, 80.98; H, 6.37; N, 5.90. Found: C,
80.92; H, 6.41; N, 5.97.
Benzophenone O-2-(Naphthalen-2-yloxy)ethyloxime (1c)
Column chromatography (silica gel, EtOAc–n-hexane, 1:20) af-
forded 1c (2.49 g, 68%) as a white solid; mp 97.4 °C; Rf = 0.60
(EtOAc–n-hexane, 1:2).
MS (EI): m/z (%) = 235 (54) [M+].
Anal. Calcd for C16H13NO: C, 81.68; H, 5.57; N, 5.95. Found: C,
81.74; H, 5.53; N, 5.90.
IR (KBr): 3065, 2927, 2864, 1657, 1449 cm–1.
9H-Fluoren-9-one O-1-(1H-Imidazol-1-yl)-3-phenoxypropan-2-
yloxime (1i)
Column chromatography (silica gel, EtOAc–n-hexane, 4:1) afford-
ed 1i (1.89 g, 48%) as a yellow oil; Rf = 0.23 (EtOAc–n-hexane,
8:1).
IR (liquid film): 3055, 2942, 2865, 1663, 1458 cm–1.
1H NMR (250 MHz, CDCl3): d = 4.43 (t, J = 5.0 Hz, 2 H, CH2ON),
4.63 (t, J = 5.0 Hz, 2 H, CH2OAr), 7.23–7.58 (complex, 14 H, aryl),
7.74–7.83 (m, 3 H, aryl).
13C NMR (62.5 MHz, CDCl3): d = 66.53, 72.71, 106.80, 107.01,
119.07, 123.71, 126.40, 126.84, 127.69, 127.93, 128.10, 128.30,
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One-Pot Synthesis of Oxime Ethers
1729
1H NMR (250 MHz, CDCl3): d = 4.00–4.07 (m, 1 H, CHON), 4.19–
4.36 (m, 2 H, NCH2), 4.50–4.55 (m, 2 H, PhOCH2), 6.90–6.99
(complex, 5 H, H4imid, H5imid, aryl), 7.22–7.26 (m, 4 H, aryl), 7.39–
7.43 (m, 4 H, aryl), 7.61–7.66 (complex, 3 H, H2imid, aryl).
13C NMR (62.5 MHz, CDCl3): d = 46.62, 56.51, 65.48, 114.55,
114.60, 120.03, 121.51, 121.77, 121.84, 127.99, 128.39, 128.58,
129.36, 129.56, 129.61, 129.69, 131.52, 131.90, 131.95, 134.96,
141.53, 153.77, 158.06.
Anal. Calcd for C20H28N4O5: C, 59.39; H, 6.98; N, 13.85. Found: C,
59.46; H, 6.94; N, 13.89.
Propan-2-one O-2-(Naphthalen-2-yloxy)ethyloxime (1o)
Column chromatography (silica gel, EtOAc–n-hexane, 1:20) af-
forded 1o (1.67 g, 69%) as a white foam; Rf = 0.50 (EtOAc–n-hex-
ane, 1:5).
IR (liquid film): 3055, 2986, 2862, 1665, 1451 cm–1.
MS (EI): m/z (%) = 395 (21) [M+].
1H NMR (250 MHz, CDCl3): d = 1.75 (s, 6 H, 2 Me), 4.16 (t, J = 5.0
Hz, 2 H, CH2ON), 4.29 (t, J = 5.0 Hz, 2 H, CH2OAr), 7.01–7.31 (m,
4 H, aryl), 7.57–7.64 (m, 3 H, aryl).
13C NMR (62.5 MHz, CDCl3): d = 21.89, 29.19, 66.58, 71.67,
106.59, 106.87, 119.10, 123.55, 126.37, 126.75, 127.67, 129.04,
129.38, 155.64, 156.96.
Anal. Calcd for C25H21N3O2: C, 75.93; H, 5.35; N, 10.63. Found: C,
75.97; H, 5.30; N, 10.68.
9H-Fluoren-9-one O-Isopropyloxime (1j)
Column chromatography (silica gel, EtOAc–n-hexane, 1:20) af-
forded 1j (1.32 g, 56%) as a pale-yellow oil; Rf = 0.36 (EtOAc–
n-hexane, 1:5).
IR (liquid film): 3064, 2970, 2857, 1658, 1469 cm–1.
1H NMR (250 MHz, CDCl3): d = 1.30 (d, J = 6.2 Hz, 6 H, 2 Me),
4.44–4.59 (m, 1 H, CHON), 7.11–7.18 (m, 4 H, aryl), 7.40–7.44 (m,
2 H, aryl), 7.64–7.65 (m, 1 H, aryl), 8.16–8.17 (m, 1 H, aryl).
13C NMR (62.5 MHz, CDCl3): d = 21.93, 77.60, 119.79, 119.85,
121.52, 127.80, 128.11, 129.15, 129.55, 130.65, 130.72, 135.95,
140.10, 141.25, 151.52.
MS (EI): m/z (%) = 243 (41) [M+].
Anal. Calcd for C15H17NO2: C, 74.05; H, 7.04; N, 5.76. Found: C,
74.12; H, 7.08; N, 5.70.
1,3-Diphenylpropan-2-one O-(2-Methylbenzyl)oxime (1p)
Column chromatography (silica gel, EtOAc–n-hexane, 1:20) af-
forded 1p (2.50 g, 76%) as a pale-yellow foam; Rf = 0.75 (EtOAc–
n-hexane, 1:5).
IR (liquid film): 3070, 2958, 2852, 1659, 1457 cm–1.
MS (EI): m/z (%) = 237 (58) [M+].
1H NMR (250 MHz, CDCl3): d = 2.78 (s, 3 H, Me), 3.87 (s, 2 H,
PhCH2), 4.07 (s, 2 H, PhCH2), 5.71 (s, 2 H, CH2ON), 7.51–7.66 (m,
14 H, aryl).
13C NMR (62.5 MHz, CDCl3): d = 19.49, 33.60, 40.07, 74.58,
126.31, 126.90, 127.19, 128.46, 129.02, 129.22, 129.41, 129.63,
129.72, 130.66, 136.49, 136.99, 137.22, 137.42, 158.55.
Anal. Calcd for C16H15NO: C, 80.98; H, 6.37; N, 5.90. Found: C,
81.02; H, 6.31; N, 5.98.
1-(4-Nitrophenyl)ethanone O-Allyloxime (1m)
Column chromatography (silica gel, EtOAc–n-hexane, 1:20) af-
forded 1m (1.71 g, 78%) as a yellow solid; mp 50.3 °C; Rf = 0.74
(EtOAc–n-hexane, 1:5).
MS (EI): m/z (%) = 329 (36) [M+].
Anal. Calcd for C23H23NO: C, 83.85; H, 7.04; N, 4.25. Found: C,
83.93; H, 7.09; N, 4.20.
IR (KBr):3058, 2936, 2857, 1659, 1445 cm–1.
1H NMR (250 MHz, CDCl3): d = 2.26 (s, 3 H, Me), 4.72 (d, J = 5.7
Hz, 2 H, CH2ON), 5.22–5.37 (complex, 2 H, =CH2), 5.97–6.12 (m,
1 H, =CH), 7.78 (d, J = 8.9 Hz, 2 H, aryl), 8.16 (d, J = 8.9 Hz, 2 H,
aryl).
13C NMR (62.5 MHz, CDCl3): d = 12.42, 75.59, 117.78, 123.53,
126.68, 133.97, 142.57, 147.91, 152.68.
Acknowledgment
We wish to thank the Shiraz University of Technology and Shiraz
University Research Councils for partial support of this work.
MS (EI): m/z (%) = 220 (68) [M+].
References
Anal. Calcd for C11H12N2O3: C, 59.99; H, 5.49; N, 12.72. Found: C,
59.91; H, 5.54; N, 12.79.
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IR (KBr): 3052, 2980, 2874, 1660, 1438 cm–1.
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M. N. Soltani Rad et al.
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Synthesis 2010, No. 10, 1724–1730 © Thieme Stuttgart · New York