New fragmentation of 2-isoxazoline-5-carboxylic acid chlorides

Article abstract of DOI:10.1002/jhet.5570430240

A novel base promoted degradation of 3-aryl-2-isoxazoline-5-carboxylic acid chlorides to aryl nitriles has been discovered.

Full text of DOI:10.1002/jhet.5570430240

Mar-Apr 2006
509
New Fragmentation of 2-Isoxazoline-5-Carboxylic Acid Chlorides
W. M. Goꢀꢁbiewski and M. Gucma
Institute of Industrial Organic Chemistry, 03-236 Warsaw, Poland
Received July 22, 2005
A novel base promoted degradation of 3-aryl-2-isoxazoline-5-carboxylic acid chlorides to aryl nitriles
has been discovered.
J. Heterocyclic Chem., 43, 509 (2006).
Amides of heterocyclic acids frequently show
biological activity [1-3]. Whilst attempting to prepare
anilides of 3-aryl-2-isoxazoline-5-carboxylic acids we
found, that reaction of the corresponding 5-acyl chlorides
with weakly nucleophilic anilines in the presence of
triethylamine (TEA) resulted in formation of a mixture of
compounds of which the expected amides were only
minor components. Composition of the reaction products
depended on the nature of the aromatic substituents. In
case of an electron donating alkyl substituents on the aryl
isoxazole (ca 0.5%). The level of the isoxazole was
increased to 6% when sodium hydride was added to the
reaction mixture. These results prompted us to investigate
the action of TEA and other bases on 3-aryl-2-isoxazo-
line-5-carboxylic acid chlorides, which were easily
prepared from esters produced in 1,3-dipolar cyclo-
addition of nitrile oxides and acrylates (Scheme 1).
To examine the influence of aniline on the course of the
reaction it was carried out by heating acyl chloride with
TEA without any derivative of aniline. Once again,
aromatic nitriles were the major products as expected,
though composition of the oligomeric products was
changed. 3-Aryl-2-isoxazolines were isolated only in
reactions involving alkylphenyl substituted acid chlorides.
The formation of 3-arylisoxazoles did not depend on the
character of the aromatic substituents. Formation of
arylnitriles from 3-arylisoxazoline-5-carboxylic acid
ring
a major product was the 4-alkylbenzonitrile
accompanied by up to 6% of 3-aryl-2-isoxazoline and
several oligomeric compounds formed due to competitive
formation of ketenes and their reactions [4]. When an
aromatic electron withdrawing substituent (CF3) was
present most of the product was oligomeric material
containing a small amount of 3-(4-trifluoromethylphenyl)-

510
W. M. Goꢀꢁbiewski and M. Gucma
Vol 43
chlorides on TEA treatment is unprecedented. The
reaction tolerates a wide range of substituents including
alkyl, halogenated alkyl, alkoxyl and halide groups on the
aryl substituent. It can be triggered by H-5 capture, and
involves cleavage of the N-O and C3-C4 bonds (Scheme
2). We were unable to isolate the other product of 2-
isoxazoline ring fragmentation, pyruvic acid chloride, e.g.
as an anilide 7 formed with p-methoxyaniline, in a pure
state. However, proton NMR spectrum of an impure
fraction from column chromatography of products
obtained from reaction of 3f acyl chloride contained
signals which could be ascribed to 4-methoxypyruvanilide
7 (singlets at 2.22 and 3.81 ppm). The yield of unstable
pyruvamide was low. It is conceivable that initially
formed acyl chloride undergoes cyclisation to 3-methyl-
oxiranone-2 prone to anionic polymerization or copolimer-
ization with ketenes formed in a competitive reaction from
2-isoxazoline acyl chlorides.
3-Aryl-2-isoxazolines 6a and 6b could be formed by
hydrolysis of acyl chlorides followed by decarboxylation.
The amount of these products was increased substantially
when the TEA was dried over KOH pellets.
More unusual is formation in relatively mild conditions
of 3-aryl isoxazoles. Hydro-chloroformyl elimination
from acyl halides is a known reaction requiring usually
high temperatures and presence of rhodium or palladium
catalyst [6-9]. Acyl chlorides containing a ꢀ hydrogen
atom are converted to olefins with loss of HCl and CO. A
driving force in the observed transformation could be
formation of a stable conjugated aromatic-heteroaromatic
system.
Further studies are under way to examine closer this
reaction.
EXPERIMENTAL
Reagent grade chemicals were used without further
purification unless otherwise noted. Elemental analyses were
performed at Microanalysis Laboratory of Institute of Organic
Chemistry, Polish Academy of Sciences, Warsaw. Melting
points were determined in capillary tubes and are uncorrected.
Spectra were obtained as follows: IR spectra on JASCO FTIR-
1
420 spectrometer, H NMR spectra on Varian 500 UNITY plus-
500 and Varian 200 UNITY plus 200 spectrometers in
deuterated chloroform using TMS as internal standard, EI mass
spectra on AMD M-40. Flash-chromatography was carried out
using silica gel S 230-400 mesh (Merck).
Hydroximinoyl acid chlorides were prepared from the
corresponding aryl aldehyde oximes and NCS in DMF [10]. The
corresponding nitrile oxides were generated in situ by
dehydrohalogenation with triethylamine.
General Procedure for the Cycloaddition Reactions of
Hydroximinoyl Acid Chlorides with Ethyl Acrylate.
Introduction of a second substituent, such as methyl
group, into the position -5 of isoxazoline acyl chloride
3g resulted in formation in the expected reaction of 3-
(4-trifluoromethylphenyl)-5-methylisoxazole (5c) (13%)
together with oligomeric compounds. In the case of an
electron donating substituent, such as ethyl group,
fragmentation of the corresponding acyl chloride 3h
afforded inter alia isoxazole 5d. In both cases no aryl
nitrile was detected underlying the role of H-5 acidity.
Other tertiary amines are also acceptable as bases.
When TEA was replaced by diisopropylethylamine
(DIPEA) the yield of arylnitrile produced from acyl
chloride 3e was increased (from 49 to 61%). Inorganic
bases such as sodium hydride proved less appropriate
for this transformation, probably due to heterogenous
reaction conditions. 3-(2-Methoxyphenyl)isoxazole was
isolated as only non-oligomeric product apart from
parent carboxylic acid 2e.
A solution of chloro oxime (13 mmol) in anhydrous toluene
(15 mL) was added dropwise over 30 min. to a stirred mixture of
anhydrous toluene, anhydrous NEt3 (6 mL), MgSO4 (2 g) and
ethyl acrylate (8 mL, 80 mmol). The reaction mixture was
stirred overnight at room temperature, diluted with toluene (50
mL), washed with water (5 x 100 mL) and evaporated in vacuo.
Ethyl 3-phenyl-4,5-dihydroisoxazole-5-carboxylate (1a).
This compound was obtained as an oil, (91%); 3070, 761, 692
(Ph), 1739 (CO) cm-1; 1H nmr (CDCl3, 200 MHz): ꢁ 7.7-7.65 (m,
2H), 7.44-7.38 (m, 3H), 5.16 (dd, J = 10.0; 8.2 Hz, 1H, H-5),
4.26 (q, J = 7.1 Hz, 2H, OCH2), 3.64 (dd, J = 10.0; 8.2 Hz, 2H,
H-4), 1.32 (t, J = 7.1 Hz, 3H).
Ethyl 3-(4-ethylphenyl)-4,5-dihydroisoxazole-5-carboxylate (1b).
This compound was obtained as a white powder, (87%), mp
1
33-35 °C; ir (KBr) 3040, 828 (Ph), 1758 (CO) cm-1; H nmr
(CDCl3, 200 MHz): ꢁ 7.60 (dm, J = 8.3 Hz, 2H, H-2', H-6'), 7.23
(dm, J = 8.3 Hz, 2H, H-3', H-5'), 5.14 (dd, J = 10.0; 8.4 Hz, 1H,
H-5), 4.26 (q, J = 7.2 Hz, 2H, CH2), 3.63 (d, J = 8.4 Hz, 1H, H-
4), 3.625 (d, J = 10.0 Hz, 1H, H-4), 2.67 (q, J = 7.6 Hz, 2H,
CH2-Ph), 1.32 (t, J = 7.2 Hz, 3H, CH3CH2O), 1.24 (t, J = 7.6 Hz,
A
similar fragmentation reaction was reported
previously for 3-aryl-5-acyl-2-isoxazolines [5].

Mar-Apr 2006
New Fragmentation of 2-Isoxazoline-5-Carboxylic Acid Chlorides
511
3H, ArylCH2CH3). eims: m/z (%) 247 (M+, 19), 174 (M+-
COOC2H5, 100), 146(M+ -COOC2H5 -C2H4, 52).
Anal. Calcd. For C14H17NO3: C, 67.99; H, 6.93. Found: C,
68.01; H, 6.97.
Anal. Calcd. For C14H14NO3F3: C, 55.81; H, 4.68. Found: C,
55.56; H, 4.51.
Methyl 3-(4-ethylphenyl)-4,5-dihydroisoxazole-5-methyl-5-
carboxylate (1h).
Ethyl 3-(4-isopropylphenyl)-4,5-dihydroisoxazole-5-carboxylate
(1c).
This compound was obtained as an oil (87%); ir (neat) 3040,
1
834 (Ph), 1741 (CO) cm-1; H nmr (CDCl3, 200 MHz): ꢀ 7.58
This compound was obtained as a yellow oil, (90%); ir (neat)
1
(dm, J = 8.4 Hz, 2H, H-2', H-6'), 7.23 (dm, J = 8.4 Hz, 2H, H-3',
H-5'), 3.88 (d, J = 17.0 Hz, 1H, H-4), 3.81 (s, 3H, OCH3), 3.21
(d, J = 17.0 Hz, 1H, H-4), 2.67 (q, J = 7.6 Hz, 2H, CH2-Ph), 1.71
(s, 3H, C-CH3), 1.24 (t, J = 7.6 Hz, 3H, EtO).
Anal. Calcd. For C14H15NO3: C, 68.55; H, 6.16. Found: C,
68.73; H, 6.03.
3040, 834 (Ph), 1739 (CO) cm-1; H nmr (CDCl3, 200 MHz): ꢀ
7.61 (dd, J = 8.3; 1.9 Hz, 2H, H-5', H-3'), 7.26 (dd, J = 8.3; 1.7
Hz, 2H, H-6', H-2'), 5.15 (dd, J = 10.0; 8.2 Hz, 1H, H-5), 4.26
(q, J = 7.0 Hz, 2H, -O-CH2), 3.63 (d, J = 8.2 Hz, 1H, H-4), 3.62
(d, J = 10.0 Hz, 1H, H-4), 2.92 (septuplet, J = 7.2 Hz, 1H, CH
iPr), 1.32 (t, J = 7.2 Hz, 3H, CH3 Et), 1.26 (d, J = 7.2 Hz, 6H,
CH3 iPr).
General Procedure for Hydrolysis of Ethyl Esters 1a-h.
Anal. Calcd. For C15H19NO3: C, 68.94; H, 7.33. Found: C,
69.09; H, 7.25.
To a suspension of an ethyl ester in mixture of ethanol and
water 1:1 was added a solution of sodium hydroxide (2.5-3 eq.)
in water and the mixture was heated at reflux for 1.5-3 hours.
The solution was cooled, extracted with ether and the ethereal
extracts were discarded. The aqueous layer was acidified with
dilute hydrochloric acid and the product, which separated, was
extracted with methylene chloride. The combined extracts were
washed with water, dried (magnesium sulfate) and evaporated in
vacuo to yield a solid, which was used directly in the next step.
An analytical sample was prepared by recrystallization.
Ethyl 3-(4-trifluoromethylphenyl)-4,5-dihydroisoxazole-5-car-
boxylate (1d).
This compound was obtained as a oil (81%); ir (neat) 3040,
841 (Ph), 1741 (CO) cm-1; 1H nmr (CDCl3, 200 MHz): ꢀ 7.79 (d,
J = 8.5 Hz, 2H, H-3', H-5'), 7.67 (d, J = 8.5 Hz, 2H, H-2', H-6'),
5.22 (dd, J = 11.0; 8.5 Hz, 1H, H-5), 4.28 (q, J = 7.0 Hz, 2H,
CH2), 3.67 (d, J = 8.5 Hz, 1H, H-4), 3.65 (d, J = 11.0 Hz, 1H, H-
4), 1.33 (t, J = 7.0 Hz, 3H, CH3); eims: m/z (%) 287 (M+, 10),
268 (M+-F, 5), 214 (M+-CO2Et, 100), 186 (M+- CO2Et-C2H4, 80),
145 (C6H5CF3, 60).
3-Phenyl-4,5-dihydroisoxazole-5-carboxylic acid (2a).
This compound was obtained as a white powder (87%), mp
124-127 °C; ir (KBr) 3600-2600 1728 (COOH), 3050, 755,
Anal. Calcd. For C13H12NO3F3: C, 54.36; H, 4.21. Found: C,
54.51; H, 4.36.
1
692(Ph) cm-1; H nmr (CDCl3, 200 MHz): ꢀ 7.70-7.65 (m, 2H,
H-2', H-6'), 7.47-7.39 (m, 3H, H-3'-H-5'), 5.24 (dd, J = 10.0; 7.8
Hz, 1H, H-5), 3.73 (d, J = 10.0 Hz, 1H, H-4), 3.72 (d, J = 7.8
Hz, 1H, H-4).
Ethyl 3-(2-methoxyphenyl)-4,5-dihydroisoxazole-5-carboxylate
(1e).
This compound was obtained as a oil, (88%); ir (neat) 3040,
1
3-(4-Ethylphenyl)-4,5-dihydroisoxazole-5-carboxylic acid (2b).
1602, 1491, 755 (Ph), 1740 (CO) cm-1; H nmr (CDCl3, 200
MHz): ꢀ 7.76 (m, 1H, H-3'), 7.36 (m, 1H, H-5'), 7.02-6.84 (m,
2H, H-4', H-6'), 5.11 (dd, J = 10.6; 8.0 Hz, 1H, H-5), 4.27 (q, J =
7.1 Hz, 2H, OCH2), 3.86 (s, 3H, OCH3), 3.75 (d, J = 10.6, 1H,
H-4), 3.74 (d, J = 8.0 Hz, 1H, H-4), 1.32 (t, J = 7.1 Hz, 3H, Et).
This compound was obtained as a white powder (89%), mp
1
105-107 °C; ir (KBr) 3500-2800, 1730 (COOH) cm-1; H nmr
(CDCl3, 200 MHz): ꢀ 7.97 (d, J = 8.4 Hz, 2H, H-3', H-5'), 7.76
(d, J = 8.4 Hz, 2H, H-2', H-6'), 7.29 (s, 1H, H-4), 2.68 (q, J = 7.0
Hz, 2H, CH2), 1.45 (t, J = 7.0 Hz, 3H, CH3); eims: m/z (%) 285
(M+, 18), 266 M+-F, 4), 212 (M+-CO2Et, 100), 184 (M+- CO2Et-
C2H4, 18), 145 (C6H5CF3, 21).
Ethyl 3-(2,3,6-trichlorophenyl)-4,5-dihydroisoxazole-5-car-
boxylate (1f).
This compound was obtained as a dense oil (74%); ir (neat)
3080, 820 (Ph), 1741 (CO), 580, 520 cm-1 (Cl); 1H NMR (CDCl3
, 200 MHz): ꢀ 7.49 (d, J = 8.8 Hz, 1H, H-4'), 7.33 (d, J = 8.8 Hz,
1H, H-5'), 5.26 (dd, J = 10.0; 8.0 Hz, 1H, H-5), 4.30 (q, J = 7.2
Hz, 2H, CH2), 3.58 (d, J = 8.0 Hz, 1H, H-4), 3.57 (d, J = 10.0
Hz, 1H, H-4), 1.35 (t, J = 7.2 Hz, 3H).
Anal. Calcd. For C12H13NO3: C, 65.74; H, 5.98. Found: C,
65.78; H, 6.00.
3-(4-Isopropylphenyl)-4,5-dihydroisoxazole-5-carboxylic acid (2c).
This compound was obtained as a glass (95%), ir (KBr) 3500-
2800, 1730 (COOH) cm-1; 1H nmr (CDCl3, 200 MHz): ꢀ 9.19 (s,
1H, OH), 7.60 (dd, J = 6.6; 1.8 Hz, 2H, H-3', H-5'), 7.27 (dd, J =
6.6; 1.8 Hz, 2H, H-2', H-6'), 5.21 (dd, J = 9.8; 7.9 Hz, 1H, H-5),
3.70 (d, J = 9.8 Hz, 1 H, H-4), 3.69 (d, J = 7.9 Hz, 1H, H-4),
2.93 (septuplet, J = 6.8 Hz, 1H, CH iPr), 1.25 (d, J = 6.8 Hz, 6H,
CH3 iPr).
Anal. Calcd. For C12H10NO3Cl3: C, 44.68; H, 3.12. Found: C,
44.49; H, 3.02.
Ethyl 3-(4-trifluoromethylphenyl)-5-methyl-4,5-dihydroisoxazole-
5-carboxylate (1g).
This compound was obtained similarly starting from ethyl
methacrylate as a dense yellowish oil, (86%); ir (KBr) 3040, 835
(Ph), 1736 (CO) cm-1; 1H nmr (CDCl3, 200 MHz): ꢀ 7.78 (d, J =
8.4 Hz, 2H, H-3', H-5'), 7.67 (d, J = 8.4 Hz, 2H, H-2', H-6'), 4.27
(q, J = 7.2 Hz, 2H,-OCH2), 3.91 (d, J = 17.0 Hz, 1H, H-4), 3.22
(d, J = 17.0 Hz, 1H, H-4), 1.74 (s, 3H, CH3), 1.33 (t, J = 7.1 Hz,
3H, Et); eims: m/z (%) 301 (M+ , 6), 282 (M+-F, 6), 228 (M+-
CO2Et, 64), 145 (C6H4CF3).
Anal. Calcd. For C13H15NO3 x ꢀ H2O: C, 64.44; H, 6.66.
Found: C, 64.54; H, 6.47.
3-(Trifluoromethylphenyl)-4,5-dihydroisoxazole-5-carboxylic
acid (2d).
This compound was obtained as a white powder (87%), mp
139-141 °C; ir (KBr) 3600-2800, 1729 (COOH), 1336 (CF3)
cm-1; 1H nmr (CDCl3, 200 MHz): ꢀ 7.80 (d, J = 8.4 Hz, 2H, H-3',

512
W. M. Goꢀꢁbiewski and M. Gucma
Vol 43
H-5'), 7.69 (d, J = 8.4 Hz, 2H, H-2', H-6'), 5.30 (dd, J = 9.5; 8.2
Hz, 1H, H-5), 3.74 (d, J = 9.5 Hz, 1 H, H-4), 3.73 (d, J = 8.2 Hz,
1H, H-4).
Anal. Calcd. For C11H8NO3F3: C, 50.97; H, 3.11. Found: C,
51.22; H, 3.26.
Benzonitrile (4a).
This compound was obtained as an oil (28%); ir (neat) 3037,
1492, 757, 688 (Ph), 2230 (CN) cm-1; 1H nmr (CDCl3, 200
MHz): ꢀ 7.67 (m, 2H, H-2, H-6), 7.51 (m, 3H, H-3-5).
4-Ethylbenzonitrile (4b).
3-(2-Methoxyphenyl)-4,5-dihydroisoxazole-5-carboxylic acid (2e).
This compound was obtained as an oil (33%); ir (neat) 2228
1
This compound was obtained as a white powder (79%), mp 74-77
°C; ir (KBr) 3600-2400, 1737 (COOH), 1602, 1491, 755 (Ph) cm-1;
1H nmr (CDCl3, 200 MHz) ꢀ 7.73 (m, 1H, H-6'), 7.40 (m, 1H, H-4'),
7.03-6.86 (m, 2H, H-3', H-5'), 5.17 (dd, J = 10.4; 7.3 Hz, 1H, H-5),
3.80 (d, J = 10.4 Hz, 1H, H-4), 3.79 (d, J = 7.3 Hz, 1H, H-4).
Anal. Calcd. For C11H11NO4 x ꢂ H2O: C, 57.38; H, 5.26.
Found: C, 57.07; H, 4.87.
(CN) cm-1; H nmr (CDCl3, 200 MHz): ꢀ 7.57 (dm, J = 8.5 Hz,
2H, H-2, -H-6), 7.29 (dm, J = 8.5 Hz, 2H, H-3, H-5), 2.71 (q, J =
7.5 Hz, 2H), 1.25 (t. J = 7.5 Hz, 3H); 13C nmr (CDCl3, 50.3
MHz): ꢀ 149.8 (C-4), 132.2 (C-3, C-5), 128.6 (C-2, C-6), 119.2
(CN), 109.5 (C-1), 29.0 (CH2), 15.0 (CH3).
4-Isopropylbenzonitrile (4c).
This compound was obtained as an oil (12%); ir (neat) 3020,
1
3-(2,3,6-Trichlorophenyl)-4,5-dihydroisoxazole-5-carboxylic
acid (2f).
1609, 1504, 835 (Ph), 2228 (CN) cm-1; H nmr (CDCl3, 200
MHz): ꢀ 7.58 (dm, J = 8.3 Hz, 2H, H-2', H-6'), 7.32 (dm, J = 8.3
Hz, 2H, H-3', H-5'), 2.96 (septuplet, J = 6.8 Hz, 1H), 1.26 (d, J =
6.8 Hz, 6H).
This compound was obtained as a white powder (87%), mp
88-90 °C; ir (KBr) 3600-2500, 1731 (COOH), 819, 523 cm-1; 1H
NMR (CDCl3, 200 MHz): ꢀ 7.50 (d, J = 8.6 Hz, 1H, H-4'), 7.34
(d, J = 8.6 Hz, 1H, H-5'), 5.33 (dd, J = 11.2; 6.8 Hz, 1H, H-5),
4.30 (q, J = 7.2 Hz, 2H, CH2), 3.66 (d, J = 11.2 Hz, 1H, H-4),
3.62 (d, J = 6.8 Hz, 1H, H-4).
2-Methoxybenzonitrile (4d).
This compound was obtained as an oil (49%); ir (neat) 3042,
1
1599, 1495, 760 (Ph), 2227 (CN) cm-1; H nmr (CDCl3, 200
MHz): ꢀ 7.6-7.5 (m, 2H, H-4, H-6), 7.05-6.91 (m, 2H, H-3, H-
Anal. Calcd. For C10H6NO3Cl3: C, 40.78; H, 2.05. Found: C,
40.62; H, 2.11.
5), 3.94 (s, 3H, CH3).
3-(Trifluoromethylphenyl)-5-methyl-4,5-dihydroisoxazole-5-
carboxylic acid (2g).
2,3,6-Trichlorobenzonitrile (4e).
This compound was obtained as an oil (51%); ir (neat) 2227
(CN) cm-1; 1H nmr (CDCl3, 200 MHz): ꢀ 7.65 (d, J = 8.8 Hz, 1H,
H-4), 7.40 (d, J = 8.8 Hz, 1H, H-5).
This compound was obtained as a white powder (87%), mp
1
164-166 °C; ir (KBr) 3422, 1716 (COOH), 838 cm-1; H nmr
(CDCl3, 200 MHz): ꢀ 7.77 (d, J = 8.4 Hz, 2H, H-3', H-5'), 7.68
(d, J = 8.8 Hz, 2H, H-2', H-6'), 3.91 (d, J = 17.3 Hz, 1H, H-4),
3.31 (d, J = 17.3 Hz, 1H, H-4), 1.80 (s, 3H, CH3-C-); eims: m/z
(%) 273 (M+, 10), 254 (M+-F, 7), 228 (M+-CO2H, 48), 186 (76),
145 (C6H4CF3, 22).
3-(4-Trifluoromethylphenyl)isoxazole (5a).
This compound was obtained as an oil (0.3%); 1H nmr
(CDCl3, 200 MHz): ꢀ 8.52 (d, J = 1.8 Hz, 1H, H-5), 7.96 (dm, J
= 8.2 Hz, 2H, H-2', H-6'), 7.74 (dm, J = 8.2 Hz, 2H, H-3', H-5'),
6.72 (d, J = 1.8 Hz, 1H, H-4).
Anal. Calcd. For C10H6ONF3: C, 56.34; H, 2.84. Found: C,
56.16; H, 2.93.
Anal. Calcd. For C12H10NO3F3: C, 52.75; H, 3.69. Found: C,
52.73; H, 3.84.
3-(4-Ethylphenyl)-4,5-dihydroisoxazole-5-methyl-5-carboxylic
acid (2h).
3-(2-Methoxyphenyl)isoxazole (5b).
This compound was obtained as a white powder (95%), mp
1
84-87 °C; ir (KBr) 3300-2500, 1699 (COOH), 833 cm-1; H
This compound was obtained as an oil (2%); ir (neat) 3070, 800
(Ph), 1259 (OMe) cm-1; 1H nmr (CDCl3, 200 MHz): ꢀ 8.44 (d, J =
1.6 Hz, 1H, H-5), 7.72 (m, 1H, H-3'), 7.43 (m, 1H, H-5'), 7.00 (m,
2H, H-4', H-6'), 6.87 (d, J = 1.6 Hz, 1H, H-4), 3.91 (s, 3H).
Anal. Calcd. For C10H9NO2: C, 68.55; H, 5.18. Found: C,
68.83; H, 5.34.
NMR (CDCl3, 200 MHz): ꢀ 7.56 (dm, J = 8.2 Hz, 2H, H-2', H-
6'), 7.24 (dm, J = 8.2 Hz, 2H, H-3', H-5'), 3.88 (d, J = 17.3 Hz,
1H, H-4), 3.29 (d, J = 17.3 Hz, 1H, H-4), 2.68 (q, J = 7.6 Hz,
2H, CH2-CH3), 1.77 (s, 3H, CH3), 1.24 (t, J = 7.6 Hz, 3H, CH3).
Anal. Calcd. For C13H15NO3: C, 66.93; H, 6.48. Found: C,
67.07; H, 6.37.
3-(4-Trifluoromethylphenyl)-5-methylisoxazole (5c).
General Procedure for Preparation of Acid Chlorides and
Reaction with Triethylamine.
This compound was obtained as an oil (13%); ir (neat) 3120,
1
1610, 1332 (CF3), 849, 820 cm-1; H nmr (CDCl3 , 200 MHz): ꢀ
7.91 (d, J = 8.8 Hz, 2H, H-2', H-6'), 7.71 (d, J = 8.8 Hz, 2H, H-
3', H-5'), 6.27 (q, J = 0.6 Hz, 1H, H-4), 2.51 (d, J = 0.6 Hz, 3H,
CH3-C=).
Anal. Calcd. For C11H8NOF3: C, 58.15; H, 3.55. Found: C,
58.28; H, 3.71.
To a solution of 3-aryl-4,5-dihydroisoxazole-5-carboxylic
acid (2 mmol) in dry benzene (15 mL) was added with stirring
oxalyl chloride (10 mmol). The solution was heated at reflux for
1.5 hour. Benzene and excess of oxalyl chloride were removed
in vacuo. Dry benzene and TEA (10-30 mmol) were added and
the solution was heated at reflux for 1 hour and stirred at room
temperature overnight. The reaction mixture was washed with
water, dried (magnesium sulfate), evaporated in vacuo and the
residue was separated by column chromatography on silica gel
using hexane – ethyl acetate gradient (from 20:1 to 1:1, v/v).
3-(4-Ethylphenyl)-5-methylisoxazole (5d).
This compound was obtained as an oil (2.9%); ir (neat) 3110,
1
1610, 1332, 849, 820 cm-1; H nmr (CDCl3, 200 MHz): ꢀ 7.70
(d, J = 8.1 Hz, 2H, H-2', H-6'), 7.28 (d, J = 8.1 Hz, 2H, H-3', H-

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New Fragmentation of 2-Isoxazoline-5-Carboxylic Acid Chlorides
513
5'), 6.27 (q, J = 0.8 Hz, 1H, H-4), 2.69 (q, J = 7.6 Hz, 2H, CH2),
2.47 (d, J = 0.8 Hz, 3H, CH3-C=), 1.26 (t, J = 7.6 Hz, 3H, CH3-
CH2).
Anal. Calcd. For C12H13NO: C, 76.97; H, 6.70. Found: C,
76.71; H, 6.86.
Acknowledgements.
This work was supported in part by the Polish State
Committee for Scientific Research (Grant E-142/S/2004), what
is gratefully acknowledged.
Isoxazolines: 3-(4-Ethylphenyl)-2-isoxazoline (6a).
REFERENCES AND NOTES
This compound was obtained as an oil (1.6%); ir (neat) 3040,
1
834 (Ph), 1600 (C=N) cm-1; H nmr (CDCl3, 200 MHz): ꢀ 7.61
[1] Pesticides Manual, The British Crop Protection Council,
Alton, Hampshire, UK, 2003, Editor C. D. S. Tomlin.
[2] G. Toshio, U. Chieko, O. Yuichi and S. Katsuhiko, Japanese
Patent 2001 322,666; Chem. Abstr., 135, 368092e (2001).
[3] S. Hermann, World Patent 01 91,558 (2001); Chem. Abstr.,
136, 16717b (2002).
[4] T. T. Tidwell, Ketenes, John Wiley & Sons, New York, NY 1995.
[5] G. Bianchi, R. Gandolfi and P. Grünanger, J. Heterocyclic
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[6] J. Tsuji in Handbook of Organopalladium Chemistry for
Organic Synthesis, Vol. 2, E. Negishi, ed, John Wiley & Sons,
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[7] D. L. Egglestone, M. C. Baird, C. J. Lock and G. Turner, J.
Chem. Soc. Dalton Trans., 1576 (1977).
(dm, J = 8.4 Hz, 2H, H-2', H-6'), 7.24 (dm, J = 8.4 Hz, 2H, H-3',
H-5'), 4.48 (t, J = 10.1 Hz, 2H, H-5), 3.33 (t, J = 10.1 Hz, 2H, H-
4), 2.68 (q, J = 7.5 Hz, 2H), 1.25 (t. J = 7.8 Hz, 3H); eims: m/z
(%) 175 (M+, 100), 160 (M+-CH3, 90), 132 (M+- CH3-C2H4, 30).
Anal. Calc. For C11H13ON: C, 75.39; H, 7.48. Found: C,
75.58; H, 7.61.
3-(4-Isopropylphenyl)-2-isoxazoline (6b).
This compound was obtained as an oil (5.3%); ir (neat) 3040,
1
837 (Ph), 1605 (C=N) cm-1; H nmr (CDCl3, 200 MHz): ꢀ 7.62
(dm, J = 8.2 Hz, 2H, H-2', H-6'), 7.27 (dm, J = 8.2 Hz, 2H, H-3',
H-5'), 4.74 (t, J = 10.0 Hz, 2H, H-5), 3.33 (t, J = 10.0 Hz, 2H, H-
4), 2.94 (septuplet, J = 6.8 Hz, 1H), 1.23 (d, J = 6.8 Hz, 6H);
eims: m/z (%) 189 (M+, 45), 174 (M+-CH3, 100).
Anal. Calc. For C12H15ON: C, 76.15; H, 7.99. Found: C,
75.99; H, 8.11.
[8] J. Tsuji and K. Ohno, J. Am. Chem. Soc., 90, 94 (1968).
[9] J. Blum, S. Kraus and Y. Pickholtz, J. Organomet Chem., 33,
227 (1971).
[10] K. C. Liu, B. R. Shelton and R. K. Hove J. Org. Chem., 45,
3916 (1980).