Synthesis and properties of O-vinylamidoximes

Article abstract of DOI:10.1055/s-2001-18721

O-Vinylamidoximes 2 are synthesized from amidoximes 1 and acetylene in superbase systems (KOH/DMSO, KOH/NMP, NaOH/CsF/NMP) in a preparative yield of up to 80%. They decompose explosively above 150°C, being resistant to solvolysis in the KOH/DMSO system (100°C, 3 h) and to polymerization (AIBN, UV). Trifluoroacetylation of O-vinylbenzamidoxime 2b with (CF₃CO)₂O/pyridine gives 5-trifluoromethyl-3-phenyl-1,2,4-oxadiazole (3) in 49% yield.

Full text of DOI:10.1055/s-2001-18721

PAPER
2427
Synthesis and Properties of O-Vinylamidoximes
Synthesis of
O
-V
o
inylamidoxim
r
es is A. Trofimov,*a Elena Yu. Schmidt,a Alexander M. Vasil’tsov,a Al’bina I. Mikhaleva,a Alexey B. Zaitsev,a
Ludmila V. Morozova,a Alexander G. Gorshkov,a Jochem Henkelmann,b Jan-Dirk Arndtb
a
A. E. Favorsky Irkutsk Institute of Chemistry, Siberian Branch of the Russian Academy of Sciences, 664033 Irkutsk, Russian Federation
Fax +7(395)2396046; E-mail: bat@irioch.irk.ru
b
BASF AG, Ammoniaklaboratorium ZAR/C-M 311, 67056 Ludwigshafen, Germany
Received 21 August 2001; revised 24 September 2001
Recently, in an attempt to obtain imidazole derivatives by
analogy to pyrrole synthesis,1–4 we have found12 that ace-
tamidoxime 1a and benzamidoxime 1b react unusually
fast with acetylene (5–7 min, 75 °C) under pressure (12–
Abstract: O-Vinylamidoximes 2 are synthesized from amidoximes
1 and acetylene in superbase systems (KOH/DMSO, KOH/NMP,
NaOH/CsF/NMP) in a preparative yield of up to 80%. They decom-
pose explosively above 150 °C, being resistant to solvolysis in the
KOH/DMSO system (100 °C, 3 h) and to polymerization (AIBN, 14 atm) in the KOH/DMSO/DS superbase system to for-
UV). Trifluoroacetylation of O-vinylbenzamidoxime 2b with
mo-vinylamidoximes 2a and 2b in 26% and 59% yields,
(CF3CO)2O/pyridine gives 5-trifluoromethyl-3-phenyl-1,2,4-oxadi-
respectively.
azole (3) in 49% yield.
In this paper, we wish to report in detail on peculiarities of
the amidoxime vinylation and a general facile synthetic
route to O-vinylamidoximes 2 (Scheme 1). The effect of
the reaction conditions on the yield of O-vinylamidoxime
2b from benzamidoxime 1b in N-methylpyrrolidone
Key words: O-vinylamidoximes, amidoximes, acetylene, hetero-
cycle, superbase, vinylation, trifluoroacetylation
The
O-vinyloxime
heteroconjugated
system
(NMP) can be seen from the Table.
CH2=CHON=, in spite of its high synthetic potential1–7
and theoretical challenge8,9 (are the double bonds p-conju-
gated through the two heteroatoms?), remains understud-
ied due to the lack of corresponding preparative methods
for their synthesis. It is known1–5 that in the presence of
superbases such as KOH/DMSO ketoximes with acety-
lene form O-vinylketoximes. As far as amidoximes are
concerned, there are only scarce data on their nucleophilic
addition to acetylenes in the literature.10,11
Scheme 1
Meanwhile, O-vinylamidoximes have a promising syn-
thetic potential, particularly for heterocyclic chemistry.
Indeed their acid-catalyzed cyclization to yield 3-substi-
tuted-5-methyl-4,5-dihydro-1,2,4-oxadiazoles is capable
of further aromatization. When catalyzed by optically ac-
tive acids (e.g., camphorsulfonic acid), this cyclization
may lead to the dihydrooxadiazoles enriched with one
enantiomer, apparently useful as ligands in asymmetric
catalysis. By analogy to the rearrangement of O-vinylke-
toximes to pyrroles,1,2 O-vinylamidoximes are expected
to open a new general access to imidazoles. Rearrange-
ment of such a type admittedly was observed in the imida-
zole synthesis from amidoximes and propiolic esters.10
Imidazole N-oxide derivatives are anticipated to be pre-
pared through the oxime-nitrone rearrangement followed
by cyclization. Also, as exemplified below in this paper,
O-vinylamidoximes are prone to acylation (e.g., trifluoro-
acetylation) at the amino group to furnish, after [3,3] sig-
Table Vinylation of Benzamidoxime 1ba
M
Temp (°C)
Time (min)
HPLC Yield (%)
of 2bb
Na
73
100
100
100
100
100
72
~ 5–7
~ 5–7
~ 5–7
30
~1
Na
11
Na (+CsF)c
89 (74)
(73)
Na (+CsF)c
K
~ 5–7
30
84 (74)
71 (65)
(80)
K
Kd
~ 5–7
a Initial acetylene pressure 15–16 atm, 50 mL of NMP, 23 mmol of
oxime 1b, 20 mmol of MOH.
b Isolated yields are given in parenthesis.
c Equimolar mixture of NaOH and CsF.
d In DMSO.
matropic
rearrangement
of
an
intermediate,
trifluoromethyl oxadiazoles easily, which are otherwise
inaccessible by other ways.
Synthesis 2001, No. 16, 30 11 2001. Article Identifier:
1437-210X,E;2001,0,16,2427,2430,ftx,en;Z09401SS.pdf.
© Georg Thieme Verlag Stuttgart · New York
ISSN 0039-7881

2428
B. A. Trofimov et al.
PAPER
The experimental procedure involved the vinylation of O-Vinylamidoximes 2a and 2b are stable up to 150 °C,
benzamidoxime 1b in an autoclave in superbase system above this temperature they decompose with explosion.
MOH/NMP (M = Na, K, Cs) followed by microcolumn The products of explosive decomposition isolated from
reverse phase high performance liquid chromatography the solution in methanol are oligomers (20–26% yield,
(RP HPLC) analysis of the reaction mixture. In some cas- MM 400–450) with the element composition different
es O-vinylbenzamidoxime 2b was simultaneously isolat- from that of the initial monomers.
ed by preparative extraction with diethyl ether.
O-Vinylbenzamidoxime 2b turned out to be resistant to
As the Table shows, NaOH catalyzes the reaction only the superbase KOH/DMSO system (100 °C, 3 h). The re-
slightly. At 73 °C, the target product 2b is observed in the covered 2b was just slightly contaminated (< 5%) by the
reaction mixture only in a trace amount. At the vinylation products of its polymerization, hydrolysis and deoxima-
temperature of 100 °C, the product yield increases only up tion (benzamide). Attempts to polymerize 2b polymeriza-
to 11%. Enhancement of the catalytic system basicity by tion were unsuccessful: the monomer was completely
the in situ generation of CsOH from the NaOH/CsF ex- recovered after both boiling in benzene (6 h) in the pres-
change at 100 °C leads to an excellent yield (89%) for just ence of azoisobutyronitrile (AIBN) and UV-irradiation (4
5–7 min. With KOH as a catalyst at 100 °C, the yield is h).
84% for the same very short time. Such an instant vinyla-
O-Vinylamidoximes readily react with trifluoroacetic an-
tion is both peculiar and essential: at a longer duration (30
hydride in the presence of pyridine at room temperature in
min) the yield of 2b drops to 71%, obviously due to insta-
diethyl ether. Thus from 2b, 5-trifluoromethyl-3-phenyl-
bility of both the starting amidoxime and the product.
1,2,4-oxadiazole (5) is obtained in 49% yield (non-opti-
The yield of O-vinylamidoximes is strongly temperature mized). Unlike the trifluoroacetylation of O-vinylke-
dependent (Figure). Thus, in the vinylation of 1b, a tem- toximes,6,7 O-vinylamidoximes appear to get attacked by
perature increase from 73 °C to 83 °C leads to a 6-fold trifluoroacetyl cation first at the amide group nitrogen
yield gain (Figure, curve 1). The highest yield of 2b (82– atom to give the intermediate 3, which seemingly cyclizes
84%) is attained in the 90–100 °C range.
to oxazoline 4, further rearranging to 5 (Scheme 2). Ap-
parently, a driving force of the rearrangement is the arom-
atization energy gain.
Figure Temperature dependence of theyield of O-vinylamidoxime
(1. 2b, KOH/NMP, 5–7 min; 2. 2b, KOH/NMP, 30 min; 3. 2a, KOH/
DMSO, 5–7 min)
Scheme 2
This subtle response of the yield of O-vinylamidoximes to
the vinylation conditions is due to side reactions of deox-
imation and alkaline hydrolysis of amidoximes.
Previously5 we have shown that in the acetoxime vinyla-
tion, even trace amounts of water in alkali-NMP system
do cause hydrolytic processes.
The intermediate 3 was identified in the reaction mixture
1
by H NMR spectroscopy. The structure of oxadiazole 5
follows from its 1H, 13C and 15N NMR spectra and the pat-
terns of the electron impact-induced fragmentation.
1H (400.13 MHz), 13C (100.69 MHz) and 15N (40.55 MHz) NMR
spectra were run on a Bruker DPX 400 spectrometer in CDCl3 with
HMDS as internal standard. IR spectra were recorded on a Bruker
IFS 25 instrument. Mass spectra were run on an LKB 2091 CLC-
MS spectrometer, ionization energy 60 eV, capillary column 38 m
long, SB-5 phase, isothermal conditions, column temperature
40 °C, ion source temperature 200 °C. Chromatographic analysis
was performed using RP HPLC13 on a Milikhrom A-02 microcol-
umn liquid chromatograph (l = 75 mm, d = 2 mm, Nucleosil 100-5
For the acetamidoxime 1a vinylation in the KOH/DMSO
system (Figure, curve 3) the highest yield of O-vinylace-
tamidoxime 2a (46%) is obtained within 73–85 °C, thus
indicating that the deoximation and hydrolysis are more
pronounced in this case.
The vinylation of o-fluorobenzamidoxime 1c in the KOH/
DMSO system (74–77 °C, 5–7 min) is accompanied by
resinification to give 21% yield of 2c, seemingly owing to C18 AB, 5000–6000 theoretical plates, chrysene peak as reference).
Eluents were: (A) aqueous buffer K2HPO4 or NaOAc solutions (1–
the fluorine solvolysis with the superbase.
Synthesis 2001, No. 16, 2427–2430 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Synthesis and Properties of O-Vinylamidoximes
2429
0.5 mM, pH 2.5–7.0); (B) MeCN or MeOH; isocratic or gradient
elution at a rate of eluent discharge 0.15–0.2 mL/min, column tem-
perature 35 °C, simultaneous photometric detection at 210, 226 and
260 nm, volume of the sample introduced into the column: 2–5 L.
Anal. Calcd for C9H9FN2O: C, 59.99; H, 5.03; F, 10.54; N, 15.10.
Found: C, 60.06; H, 5.28; F 10.51; N, 15.10.
5-Trifluoromethyl-3-phenyl-1,2,4-oxadiazole (5)
To a stirred mixture of 2b (0.80 g, 5 mmol), pyridine (0.79 g, 10
mmol) and Et2O (10 mL) was added trifluoroacetic anhydride (2.10
g, 10 mmol) during 40 min at r.t. The mixture was stirred for 1.5 h
more and neutralized with aq NaHCO3 solution. The Et2O layer was
separated, the aqueous layer was extracted with Et2O and the com-
bined Et2O extracts combined were dried (MgSO4). After distilling
off the solvent, the product was purified by column chromatography
(Al2O3, hexane) to give 0.52 g (49%) of 5 in 49% yield; light-yellow
crystals; mp 62–64 °C.
1H NMR: = 8.08 (m, 2 H, Hortho), 7.56 (m, 1 H, Hpara), 7.50 (m, 2
H, Hmeta).
13C NMR: = 169.51 (C-3), 166.15 (C-5), 116.35 (CF3), 132.54
The amidoximes 1 were prepared by a known procedure.14 Com-
mercial grade DMSO, NMP (Merck, < 0.2% H2O), NaOH (< 2%
H2O), KOH ( 15% H2O) and CsF (ABCR, 99 +%) were used in the
experiments.
Vinylation of Acetamidoxime 1a; N’-(Vinyloxy)ethanimidam-
ide (2a); Typical Procedure
A steel 1 L rotating autoclave was charged with 1a (1.85 g, 25
mmol), KOH (2.25 g, 34.6 mmol) and DMSO (50 mL). The mixture
was saturated with acetylene up to 15–16 atm and heated for 30 min
to 79 °C (during this process the maximum acetylene pressure in the
autoclave approached 35 atm). Then the heating was immediately
ceased and the autoclave furnace was opened (the reaction time at
the above temperature was 5–7 min). After cooling to r.t., the mix-
ture was discharged, neutralized with solid CO2, diluted with H2O
to 100 mL and extracted with Et2O (4 20 mL). The collected Et2O
extracts were washed with H2O (3 10 mL), dried (MgSO4) and fil-
tered. The filtrate was passed through an Al2O3 column (30 3).
Evaporation of the solvent at reduced pressure gave 1.16 g of 2a;
yield: 46%; colorless oil; nD20 1.5682.
(Cpara), 129.42 (Cortho), 128.03 (Cmeta), 125.27 (Cipso).
15N NMR (40.55 MHz): (with respect to NH3) = 361.3 (N-2),
245.90 (N-4). Its 15N chemical shifts correspond to the structure of
1,2,4-oxadiazole.15
MS: m/z (%) = 215 (M+, 12%), 214 [(M – H)+, 100] 145[(M – H –
CF3)+, 34] 119, (59), 91 (52), 103 (PhCN, 15%), 77 (Ph, 45), 69
(CF3, 90).
IR (neat, cm–1): 3475s, 3340s ( NH2), 3085s ( =CH2), 1655vs (
C=N), 1630s, 1615s ( C=C), 1190s ( C–O), 1170m ( C–N),
960m ( CH=CH), 835m cm–1 ( =CH2).
Anal. Calcd for C9H5F3N2O: C, 50.48; H, 2.35; F, 26.62; N, 13.08.
Found: C, 50.16; H, 2.33; F 26.52; N, 13.09.
1H NMR: = 6.72 (dd, 1 H, - , 3J = 14.0 Hz, 3J ' = 6.8 Hz), 4.62
Evaluation of Thermal Stability of O-Vinylamidoximes 2a,b
A sample of O-vinylamidoxime 2a,b (0.35 g) sealed in a 1.5-mL
glass ampoule was placed in a brass case with a capillary opening
to discharge excess pressure and heated (bath, silicone oil) by rais-
ing the temperature at the rate of 4 °C/min. After explosion, the
heating was stopped and the case was allowed to reach r.t. A mix-
ture of finely dispersed glass fragments and a dark-brown powdery
product was collected and treated with MeOH (5 mL) and decanted.
This was repeated twice to completely recover the product. After
evaporation of MeOH and drying, the product (well soluble in
MeOH, EtOH and moderately soluble in CHCl3, DMSO) was ob-
tained and further analyzed.
-
-
(br s, 2 H, NH2), 4.55 (dd, 1 H, H- , 3J = 14.0 Hz, 2J ' = 1.6 Hz),
-
-
3
2
4.01 (dd, 1 H, H- , J = 6.8 Hz, J = 1.6 Hz), 1.85 (s, 3 H,
-
'
- '
CH3).
13
NMR (100.69 MHz): = 153.44 (1J1-Me 52.6 Hz, C-1), 153.23
(1J2-3 80.2 Hz, C-2), 85.70 (1J2-3 80.2 Hz, C-3), 16.55 (CH3).
Anal. Calcd for C4H8N2O: C, 47.99; H, 8.05; N, 27.98. Found: C,
47.88; H, 8.33; N, 28,01.
N’-(Vinyloxy)benzenecarboximidamide (2b)
Following the typical procedure for the preparation of 2a, com-
pound 1b (3.13 g, 23 mmol) was reacted with acetylene (initial acet-
ylene pressure 16 atm) for 5–7 min in the presence of KOH (1.35
g, 20.7 mmol) in DMSO (50 mL) at 72 °C; yield: 2.99 g (80%); col-
orless oil; nD20 1.5806.
IR (neat, cm–1): 3490s, 3390s ( NH2), 1645vs ( C=N), 1620m (
NH2), 1600s ( C=C), 1185s ( C–O), 960m ( CH=CH), 845m (
=CH2).
O-Vinylacetamidoxime 2a exploded at 152 °C to give 0.09 g (26%)
of oligomers (Mol. mass 400).
IR (film, cm–1): 3176s ( CONH2), 2880–2960s ( CH3,CH2),
2220w ( C N), 1669vs ( C=N), 1420s ( H–C=), 1106m
(
C–O). Broadened bands, high background. Absorption bands
were assigned according to Ref.16
Anal. Found: C, 64.4; H, 7.1; N, 14.3.
1H NMR: = 6.88 (dd, 1 H, H- , 3J = 14.0 Hz, 3J ’ = 6.8 Hz),
-
-
4.95 (br s, 2 H, NH2), 4.66 (dd, 1 H, H- , 3J = 14.0 Hz, 2J ’ = 1.6
O-Vinylbenzamidoxime 2b exploded at 153 °C to give 0.07 g
(20%) of oligomers (Mol. mass 450).
-
-
Hz), 4.13 (dd, 1 H, H- , 3J ’ = 6.8 Hz, 2J ’ = 1.6 Hz).
-
-
IR(film, cm–1): 3161vs ( CONH2), 3064s ( CH), 2924s ( C2),
2228w ( C N), 1666vs ( C=N), 1650s, 1606s, 1580s ( C=C),
1468w ( CH2), 1416w ( H–C=), 1106 m ( C–O), 775s, 751s,
710s, 693s ( , benzene ring). Broadened bands, high background,
assigned according to Ref.16
13C NMR: = 154.37 (1J1-ipso = 65.7 Hz, C-1), 153.23 (1J2-3 = 80.2
Hz, C-2), 133.08 (1J1-ipso = 65.7 Hz, Cipso), 130.70 (1Jpara-meta 55.4
Hz, Cpara), 129.07 (1Jmeta-ortho 56.4 Hz, Cmeta), 126.91 (1Jortho-ipso 58.8
Hz, Cortho), 87.36 (1J2-3 = 80.2 Hz, C-3).
Anal. Calcd for C9H10N2O: C, 66.65; H, 6.21; N, 17.27. Found: C,
66.86; H, 6.28; N, 27.10.
Anal. Found: C, 66.7; H, 6.2; N, 17.3.
2-Fluoro-N’-(vinyloxy)benzenecarboximidamide (2c)
Prepared following the typical procedure and using the same condi-
tions as for 2b;
Yield: 21%; colorless oil; nD20 1.5818.
References
(1) Trofimov, B. A.; Mikhaleva, A. I. N-Vinylpyrroles; Nauka:
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1H NMR: = 7.65–7.00 (m, 4 Harom), 6.80 (dd, 1 H, H- , 3J = 14.0
-
Hz, 3J ’ = 6.8 Hz), 5.19 (br s, 2 H, NH2), 4.60 (dd, 1 H, H- , 3J
-
-
= 14.0 Hz, 2J ’ = 1.6 Hz), 4.05 (dd, 1 H, H- , 3J ’ = 6.8 Hz, 2J
-
-
-
’
= 1.6 Hz).
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B. A. Trofimov et al.
PAPER
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Synthesis 2001, No. 16, 2427–2430 ISSN 0039-7881 © Thieme Stuttgart · New York