Unusual reactions of vinyl ketones with tetranitromethane. the synthesis of 5-acyl-3-nitroisoxazoles

Full text of DOI:10.1007/s11172-008-0276-4

Russian Chemical Bulletin, International Edition, Vol. 57, No. 9, pp. 2034—2035, September, 2008
2034
Unusual reactions of vinyl ketones with tetranitromethane.
The synthesis of 5ꢀacylꢀ3ꢀnitroisoxazoles
Yu. A. Volkova,a O. A. Ivanova,a,b E. M. Budynina,a E. B. Averina,a T. S. Kuznetsova,a,b and N. S. Zefirova,b
aDepartment of Chemistry, M. V. Lomonosov Moscow State University,
1 Leninskie Gory, 119992 Moscow, Russian Federation.
Fax: +7 (495) 939 0290. Eꢀmail: kuzn@org.chem.msu.ru
bInstitute of Physiologically Active Compounds, Russian Academy of Sciences,
1 Severnyi pr., 142432 Chernogolovka, Moscow Region, Russian Federation.
According to the literature data,1 electrophilic alkenes
are inert to tetranitromethane (TNM). Recently, we have
studied threeꢀcomponent reactions of TNM with alkenes
and showed2,3 that nitronates, which are TNM—alkene
adducts produced in the first step, are obtained only
from olefins containing electronꢀdonor substituents,
while electrophilic alkenes participate only in subsequent
[3+2] cycloaddition as dipolarophiles.
Scheme 2
In our further investigations of reactions of alkenes
with polynitromethanes, we found that methyl vinyl
ketone (1) unusually reacts with TNM in THF to give
5,5,5ꢀtrinitropentanꢀ2ꢀone (2), a product of formal addiꢀ
tion of trinitromethane to alkene 1, and 2ꢀnitrotetraꢀ
hydrofuran (3) as a nitration product of THF (Scheme 1).
R1 = H, R2 = Me (1; 7, 58%); R1 = H, R2 = Et (4; 8, 47%);
1 = H, R2 = Ph (5; 9, 85%); R1, R2 = —(CH2)3— (6; 10, 45%);
i. 1,4ꢀDioxane, Et3N (2 equiv.).
R
Scheme 3
Scheme 1
i. Et3N, 1,4ꢀdioxane—MeCN.
cursor of nitroisoxazole could be an adduct of triniꢀ
tromethane and a vinyl ketone, e.g., compound 2 (see
Scheme 1). To verify this assumption, we synthesized triꢀ
nitro derivative 2 according to a known procedure.5 However,
treatment of adduct 2 with triethylamine under various
conditions did not lead to isoxazole 7.
As a final remark, note that reactions of vinyl ketones
with TNM demonstrate, as a way of example, that electroꢀ
philic alkenes can react with TNM. The presented method
for the synthesis of 3ꢀnitroisoxazoles is not versatile but it
is feasible and involves accessible starting reagents. The
mechanism of this reaction will be a subject of our further
investigations.
In connection with this, we studied in more detail the
reactivities of conjugated ketones toward TNM and found
that the action of TNM on vinylic ketones 1 and 4—6 in
the presence of triethylamine leads to 5ꢀacylꢀ3ꢀnitroisoxꢀ
azoles 7—10 through a new pathway of heterocyclization
of electrophilic alkenes (Scheme 2).
However, attempts to use other electrophilic alkenes in
this reaction failed. Under these conditions, acrolein and
acrylonitrile polymerized, (E)ꢀ4ꢀphenylbutꢀ3ꢀenꢀ2ꢀone
did not react with TNM, and 2,3,4,5,6ꢀpentafluorostyrene
and (E)ꢀ(2ꢀnitrovinyl)benzene in reactions with TNM gave
products of the formal addition of trinitromethane in trace
amounts. Only with methyl acrylate (11) did we obtain
trinitro derivative 12 4 in low yield (Scheme 3).
1
H and 13C NMR spectra were recorded on a Bruker AMꢀ
400 spectrometer (400 and 100 MHz, respectively) in CDCl3
Thus, we discovered an unusual reaction of vinyl keꢀ
tones with TNM yielding 3ꢀnitroisoxazoles. A possible preꢀ
with chloroform as the internal standard (δ 7.28 and δ 77.1).
The course of the reactions was monitored and the purity of the
H
C
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 9, pp. 1999—2000, September, 2008.
1066ꢀ5285/08/5709ꢀ2034 © 2008 Springer Science+Business Media, Inc.

Synthesis of 5ꢀacylꢀ3ꢀnitroisoxazoles
Russ.Chem.Bull., Int.Ed., Vol. 57, No. 9, September, 2008
2035
products was checked by TLC on Silufol UVꢀ254 plates. Preparꢀ
ative column chromatography was carried out with SiO2 as
a sorbent (Acros, 60—200 mesh). Commercial alkenes 1, 4, and
5 and triethylamine were purified by distillation. Phenyl vinyl
ketone (7) and tetranitromethane were prepared as described
earlier.6,7
(m, 2 H, Ph). 13C NMR, δ: 102.9 (CH); 129.0 (CH, Ph); 130.8
(2 CH, Ph); 135.1 (CH, Ph); 134.3 (s, Ph); 163.5 (CON); 165.4
(CNO2); 182.9 (CO).
3ꢀNitroꢀ5,6ꢀdihydroꢀ1,2ꢀbenzoisoxazolꢀ7(4H)ꢀone (10).
Yield 45%, yellow crystals, m.p. 114—115 °C, Rf = 0.25 (CHCl3).
Found (%): C, 46.21; H, 3.50; N, 15.19. C7H6N2O4. Calculatꢀ
ed (%): C, 46.16; H, 3.32; N, 15.38. 1H NMR, δ: 2.26—2.29,
2.78—2.81 (both m, 2 H each, CH2); 3.17 (t, 2 H, CH2, 3J = 6.3 Hz).
13C NMR, δ: 20.3, 22.3, 39.8 (all CH2); 119.1 (s); 158.9 (CON);
160.9 (CNO2); 189.2 (CO).
Methyl 4,4,4ꢀtrinitrobutanoate (12)4 was obtained according
to the general procedure for nitroisoxazoles. The yield was
36%, yellow substance, m.p. 25—26 °C, Rf = 0.51 (light petroꢀ
leum—EtOAc, 4 : 1). 1H NMR, δ: 2.75—2.78, 3.39—3.42 (both m,
2 H each); 3.75 (s, 3 H). 13C NMR, δ: 27.9, 29.3 (both CH2);
52.4 (Me); 129.2 (C(NO2)3); 169.8 (CO).
5,5,5ꢀTrinitropentanꢀ2ꢀone (2). Tetranitromethane (0.49 g,
2.5 mmol) was added to a solution of methyl vinyl ketone (0.53 g,
7.5 mmol) in THF (8 mL) and the reaction mixture was stirred at
20 °C for 10 days. After the reaction was completed, the solvent
was removed under reduced pressure and the product was isolatꢀ
ed by column chromatography with light petroleum—EtOAc
(5 : 1) as an eluent. The yield was 25%, m.p. 44 °C (cf. Ref. 8:
1
m.p. 43—44 °C), Rf = 0.35 (CHCl3). H NMR, δ: 2.24 (s, 3 H,
Me); 2.87—2.90 (m, 2 H, CH2); 3.31—3.34 (m, 2 H,
1
CH2C(NO2)3). 13C NMR, δ: 28.7 (CH2CO, JC,H = 137 Hz);
29.7 (CH3, 1JC,H = 137 Hz); 37.3 (CH2C(NO2)3, 1JC,H = 130 Hz);
127.0 (C(NO2)3); 202.5 (CO).
This work was financially supported by the Russian
Foundation for Basic Research (Project No. 07ꢀ03ꢀ00685ꢀa)
and the Division of Chemistry and Materials Science of
the Russian Academy of Sciences (Program No. 1.5).
2ꢀNitrotetrahydrofuran (3). Yield 21%, Rf = 0.78 (CHCl3).
1H NMR, δ: 2.05—2.17 (m, 2 H, CH2); 2.20—2.30, 2.58—2.67
(both m, 1 H each, CH2); 3.98—4.08 (m, 2 H, CH2); 5.23 (t, 1 H,
CH, 3J = 7.6 Hz). 13C NMR, δ: 25.6 (CH2); 29.7 (CH2); 71.1
(CH2O); 79.7 (CH). MS, m/z = 71 [M – NO2]+. Compound 3
was not isolated in the analytically pure state.
References
Synthesis of 5ꢀacylꢀ3ꢀnitroisoxazoles 7—10 (general proceꢀ
dure). A solution of triethylamine (2.0 mmol) in dioxane (2.5 mL)
was added dropwise to a cooled mixture of an alkene (1.0 mmol)
and TNM (2.5 mmol) in dioxane (2.5 mL). Then the cooling was
off and the reaction mixture was stirred at 20 °C for 12 h. If the
reaction mixture separated into layers, acetonitrile (0.5 mL) was
added. Then the solvent was removed under reduced pressure
and the product was isolated by column chromatography with
light petroleum—EtOAc (5 : 1) as an eluent.
1ꢀ(3ꢀNitroisoxazolꢀ5ꢀyl)ethanone9 (7). Yield 58%, colorless
crystals, m.p. 70—72 °C, Rf = 0.62 (light petroleum—EtOAc,
4 : 1). 1H NMR, δ: 2.67 (s, 3 H, Me); 7.35 (s, 1 H, CH).
13C NMR, δ: 26.8 (Me); 100.3 (CH); 163.3 (CNO2); 165.7
(CON); 189.7 (C=O).
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C, 42.45; H, 3.54; N, 16.32. C6H6N2O4. Calculated (%):
C, 42.36; H, 3.55; N, 16.47. 1H NMR, δ: 1.20 (t, 3 H, Me,
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(3ꢀNitroisoxazolꢀ5ꢀyl)phenylmethanone (9). Yield 85%, colꢀ
orless crystals, m.p. 82—83 °C, Rf = 0.66 (CHCl3). Found (%):
C, 55.27; H, 2.63; N, 12.88. C10H6N2O4. Calculated (%):
C, 55.05; H, 2.77; N, 12.84. 1H NMR, δ: 7.53 (s, 1 H, CH);
7.56—7.60 (m, 2 H, Ph); 7.71—7.75 (m, 1 H, Ph); 8.31—8.33
Received September 20, 2007;
in revised form December 4, 2007