Synthesis of 2-[(Z)-1-hydropolyfluoro-1-alkenyl]-4H-3,1-benzoxazin-4-ones

Article abstract of DOI:10.1016/S0022-1139(01)00456-0

N,N′-dicyclohexylcarbodiimide induced condensation of 2,2-dihydropolyfluoroalkanoic acid and anthranilic acid or its derivatives followed by a dehydrating ring-closure reaction in the presence of Ac₂O gave 2-[(Z)-1-hydropolyfluoro-1-alkenyl]-4H-3,1-benzoxazin-4-ones in good to excellent yields.

Full text of DOI:10.1016/S0022-1139(01)00456-0

Journal of Fluorine Chemistry 111 ꢀ2001) 213±216
Synthesis of 2-[ꢀZ)-1-hydropoly¯uoro-1-alkenyl]-4H-3,
1-benzoxazin-4-ones
*
Jin-Tao Liu , He-Jun Lu
È
Laboratory of Organo¯uorine Chemistry, Shanghai Institute of Organic Chemistry,
Chinese Academy of Sciences, 354 Fenglin Lu, Shanghai 200032, China
Received 29 March 2001; accepted 29 June 2001
Abstract
N,N0-dicyclohexylcarbodiimide induced condensation of 2,2-dihydropoly¯uoroalkanoic acid and anthranilic acid or its derivatives
followed by a dehydrating ring-closure reaction in the presence of Ac2O gave 2-[ꢀZ)-1-hydropoly¯uoro-1-alkenyl]-4H-3,1-benzoxazin-4-
ones in good to excellent yields. # 2001 Elsevier Science B.V. All rights reserved.
Keywords: 2-[ꢀZ)-1-Hydropoly¯uoro-1-alkenyl]-4H-3,1-benzoxazin-4-one; 2,2-Dihydropoly¯uoroalkanoic acid; Synthesis
1. Introduction
In the presence of N,N0-dicyclohexylcarbodiimide ꢀDCC),
2,2-dihydropoly¯uoroalkanoic acids condensed with anthra-
nilic acid or its derivatives in CH2Cl2 at room temperature or
under re¯uxto give the corresponding amides ꢀ 3, major) as
well as cyclic products ꢀ4, minor). The results are summarized
in Table 1. Subsequently, treatment of the mixture with Ac2O
afforded 2-[ꢀZ)-1-hydropoly¯uoro-1-alkenyl]-4H-3,1-benzo-
xazin-4-ones in good to excellent yields ꢀScheme 2, Table 1).
Dicyclohexylurea formed in the reaction from DCC has
very low solubility in CH2Cl2 and can be removed con-
veniently from the reaction mixture by ®ltration. This
simpli®ed the procedure for the separation of the desired
product and raised the overall yield consequently.
The con®guration of the carbon±carbon double bond in
compound 4 was assigned to be the Z-form from the
coupling constant between the ole®nic hydrogen and ¯uor-
ine atom ꢀJHÀF ˆ 29:4 Hz). No E-isomer was isolated in this
reaction. The yields of 4 with short polyhaloalkyl tails were
comparatively less than those of 4 with longer tails. The
major by-product 5fh was isolated and characterized to have
the structure shown in Scheme 3, and was assumed to be
formed by the reaction of 4 with acetic acid. Interestingly,
this kind of by-product was not detected when RF is C5F11,
C3F6Cl or C3F7.
4H-3,1-Benzoxazin-4-ones have been known for more
than a century [1] and show interesting pharmacological
properties. For example, they are potent inactivators of
chymotrypsin [2] as well as inhibitors of HSV-1 protease
[3]. Since the phenyl derivative was ®rst synthesized in 1883
[4], numerous 2-substituted-4H-3,1-benzoxazin-4-ones have
been prepared. However, substituents at the C-2 position
are usually the common alkyl, alkenyl or aryl groups. The
synthesis of 2-poly¯uoroalkyl or alkenyl substituted 4H-3,1-
benzoxazin-4-ones has been comparatively less studied [5].
It is known that ¯uorine has profound and special effects on
the biological activity of organic compounds [6], so it is our
interest to develop ef®cient methods to synthesize ¯uorine-
containing 4H-3,1-benzoxazin-4-ones and their derivatives.
In this paper, we report a convenient synthesis of 2-[ꢀZ)-1-
hydropoly¯uoro-1-alkenyl]-4H-3,1-benzoxazin-4-ones
from 2,2-dihydropoly¯uoroalkanoic acid.
2. Results and discussion
2,2-Dihydropoly¯uoroalkanoic acids are versatile ¯uor-
ine-containing building blocks developed in our laboratory.
They are easily prepared from poly¯uoroalkyl iodides as
shown in Scheme 1 [7].
Boutevin et al. reported the synthesis of 4ag in 1992 [5],
but their method involved the use of C5F11CH2COCl, which
is dif®cult to handle, and the yield was low ꢀ43%). The
above reactions provide a convenient and useful route to 2-
[ꢀZ)-poly¯uoro-1-alkenyl]-4H-3,1-benzoxazin-4-ones with
high yield and stereoselectivity, mild reaction conditions
as well as easy availability of the starting material.
* Corresponding author. Fax: ‡86-21-64166128.
E-mail address: jtliu@pub.sioc.ac.cn ꢀJ.-T. Liu).
0022-1139/01/$ ± see front matter # 2001 Elsevier Science B.V. All rights reserved.
PII: S 0 0 2 2 - 1 1 3 9 ꢀ 0 1 ) 0 0 4 5 6 - 0

È
J.-T. Liu, H.-J. Lu / Journal of Fluorine Chemistry 111 ,2001) 213±216
214
Scheme 1.
Table 1
spectrometer at 56.4 MHz using TFA as external standard.
In 19F NMR spectra, chemical shifts ꢀin ppm) are regarded as
positive for up®eld shifts and the values are reported as
dCFCl ꢀdCFCl ˆ dTFA ‡ 76:8). Mass spectra were obtained
Condensation of 2,2-dihydropolyfluoroalkanoic acids with anthranilic
acids
Entry
1
2
Temperature Time ꢀh) Product
3
3
4
Yields ꢀ%)a
on a Finnigan GC-MS 4021 spectrometer. Column chroma-
tography was performed using silica gel H, particle size
10±40 mm.
1
2
1a
1b
1c
1d
1e
1f
2g
2g
2g
2g
2g
2g
2h
2h
2h
2h
2h
2h
2i
RT
RT
8.0
7.0
7.5
7.0
7.0
7.0
3.5
3.0
3.0
3.0
3.0
3.0
4ag
4bg
4cg
4dg
4eg
4fg
4ah
4bh
4ch
4dh
4eh
4fh
4ai
90.5
92.0
90.0
75.0
75.0
75.0
95.0
93.5
95.0
78.5
78.0
78.0
90.0
88.5
88.0
68.0
65.0
75.0
76.0
78.0
3
RT
3.1. Synthesis of 2-[,Z)-hydropolyfluoro-1-alkenyl]-
4H-3,1-benzoxazin-4-ones
4
RT
5
RT
RT
6
7
1a
1b
1c
1d
1e
1f
RT
Typical procedure: A mixture of 1 ꢀ1.0 mmol) and DCC
ꢀ1.1 mmol) in CH2Cl2 ꢀ10 ml) was stirred at room tempera-
ture for a few minutes. Awhite suspension was formed. Then
a solution of 2 ꢀ1.0 mmol) in CH2Cl2 ꢀ5 ml) was added
dropwise to the above suspension with stirring at room
temperature. After addition, the resulting mixture was stirred
at room temperature or under re¯uxtill the reaction was
complete ꢀmonitored by TLC). The reaction mixture was
®ltered with suction to give a clear yellow solution. After
removal of the solvent, the pale yellow solid was dissolved
in 10 ml Ac2O and the mixture was stirred under re¯ux for
1.5±2.0 h. Excess Ac2O was evaporated under vacuum and
the oily residue thus obtained was subjected to column
chromatography using light petroleum and EtOAc ꢀ20:1)
as eluant to give compound 4 as white solids.
8
RT
9
RT
RT
10
11
12
13
14
15
16
17
18
19
20
RT
RT
1a
1b
1c
1d
1e
1a
1b
1c
Reflux5.0
Reflux5.0
Reflux5.0
Reflux4.0
Reflux4.0
Reflux6.5
Reflux6.5
Reflux6.0
2i
4bi
4ci
2i
2i
4di
4ei
2i
2j
4aj
4bj
4cj
2j
2j
a Isolated yield of two steps.
3. Experimental
Melting points were uncorrected. IR spectra were taken
on a Perkin-Elmer 983G IR spectrophotometer using KBr
pellets. 1H NMR spectra were recorded on a Bruker AM 300
ꢀ300 MHz) spectrometer using TMS as internal standard.
19F NMR spectra were recorded on a Varian EM-360L
3.1.1. Compound 4ag
Mp 103±104.58C. 1H NMR ꢀCDCl3) d: 7.57±8.24 ꢀ4H, m,
ArH), 6.31 ꢀ1H, d, J ˆ 29:4 Hz, =CH) ppm; 19F NMR
ꢀCDCl3) d: 79.8 ꢀ3F, t, CF3), 106.1 ꢀ1F, m, =CF), 114.5±
122.5 ꢀ8F, m, 4CF2) ppm; IR nmax ꢀcmÀ1): 1764 ꢀC=O), 1230
Scheme 2.

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J.-T. Liu, H.-J. Lu / Journal of Fluorine Chemistry 111 ,2001) 213±216
215
Scheme 3.
‡
ꢀC±F), 1141 ꢀC±O); MS m/z ꢀ%): 459 ꢀM , 100.0), 146
ꢀ26.2); Anaysis: Found: C, 39.43; H, 1.43; N, 2.88%.
C15H5F12NO2 requires: C, 39.24; H, 1.10; N, 3.05%.
Found: C, 50.83; H, 2.06; N, 5.17%; C11H5NF4O2 requires:
C, 50.98; H, 1.94; N, 5.40%.
3.1.7. Compound 4ah
3.1.2. Compound 4bg
1
Mp 138.5±1408C. 1H NMR ꢀCDCl3) d: 7.53 ꢀ1H, s, ArH),
7.04 ꢀ1H, s, ArH), 6.27 ꢀ1H, d, J ˆ 29:4 Hz, =CH), 4.02
ꢀ3H, s, OCH3), 4.00 ꢀ3H, s, OCH3) ppm; 19F NMR ꢀCDCl3)
d: 79.3 ꢀ3F, t, CF3), 107.1 ꢀ1F, m, =CF), 117.0 ꢀ2F, m, CF2),
121.5 ꢀ4F, m, 2CF2), 124.8 ꢀ2F, m, CF2) ppm; IR nmax
ꢀcmÀ1): 1751 ꢀC=O), 1246 ꢀC±F), 1132 ꢀC±O); MS m/z
Mp 105±1078C. H NMR ꢀCDCl3) d: 7.55±8.22 ꢀ4H, m,
ArH), 6.30 ꢀ1H, d, J ˆ 29:4 Hz, =CH) ppm; 19F NMR
ꢀCDCl3) d: 66.8 ꢀ2F, t, ClCF2), 105.5 ꢀ1F, m, =CF), 116.6
ꢀ2F, m, CF2), 120.1 ꢀ2F, m, CF2) ppm; IR nmax ꢀcmÀ1): 1765
ꢀC=O), 1200 ꢀC±F); MSm/z ꢀ%): 377ꢀ34.3), 375ꢀM , 100.0),
146 ꢀ55.5); HRMS Found: 374.99088; C13H5ClF7NO2
requires: 374.98970.
‡
‡
ꢀ%): 519ꢀM , 100.0); HRMS Found: 519.03446;
C17H9F12NO4 requires: 519.03400.
3.1.3. Compound 4cg
1
3.1.8. Compound 4bh
1
Mp 105±1068C. H NMR ꢀCDCl3) d: 7.57±8.24 ꢀ4H, m,
Mp 136±1388C. H NMR ꢀCDCl3) d: 7.53 ꢀ1H, s, ArH),
ArH), 6.31 ꢀ1H, d, J ˆ 29:4 Hz, =CH) ppm; 19F NMR
ꢀCDCl3) d: 79.8 ꢀ3F, t, CF3), 106.5 ꢀ1F, m, =CF), 118.6
ꢀ2F, m, CF2), 126.3 ꢀ2F, m, CF2) ppm; IR nmax ꢀcmÀ1): 1776
ꢀC=O), 1226 ꢀC±F), 1124 ꢀC±O); MS m/z ꢀ%): 359 ꢀM ,
100.0); 146 ꢀ29.9); Analysis: Found: C, 43.45; H, 1.45; N,
4.04%; C13H5F8NO2 requires: C, 43.47; H, 1.40; N, 3.90%.
7.04ꢀ1H,s,ArH),6.26ꢀ1H,d,J ˆ 29:5 Hz,=CH),4.01ꢀ3H,s,
OCH3), 3.99 ꢀ3H, s, OCH3) ppm; 19F NMR ꢀCDCl3) d: 66.9
ꢀ2F, t, ClCF2), 107.1 ꢀ1F, m, =CF), 116.8 ꢀ2F, m, CF2), 120.1
ꢀ2F, m, CF2) ppm; IR nmax ꢀcmÀ1): 1753 ꢀC=O), 1291 ꢀC±F),
1175ꢀC±O);MSm/zꢀ%):437ꢀ37.3), 435ꢀM ,100.0);HRMS
Found: 435.01488; C15H9ClF7NO4 requires: 435.01083.
‡
‡
3.1.4. Compound 4dg
1
3.1.9. Compound 4ch
Mp 98±998C. H NMR ꢀCDCl3): d: 7.56±8.24 ꢀ4H, m,
Mp 133.5±1358C. 1H NMR ꢀCDCl3) d: 7.53 ꢀ1H, s, ArH),
7.04 ꢀ1H, s, ArH), 6.26 ꢀ1H, d, J ˆ 29:5 Hz, =CH), 4.01
ꢀ3H, s, OCH3), 4.00 ꢀ3H, s, OCH3) ppm; 19F NMR ꢀCDCl3 )
d: 79.3 ꢀ3F, t, CF3), 107.3 ꢀ1F, m, =CF), 117.8 ꢀ2F, m, CF2),
125.8 ꢀ2F, m, CF2) ppm; IR nmax ꢀcmÀ1): 1758 ꢀC=O), 1248
ArH), 6.24 ꢀ1H, d, J ˆ 28:7 Hz, =CH) ppm; 19F NMR
ꢀCDCl3): d: 60.1 ꢀ2F, d, ClCF2), 106.8 ꢀ1F, m, =CF) ppm;
IRnmaxꢀcmÀ1):1766ꢀC=O),1275ꢀC±F),1161ꢀC±O);MSm/z
ꢀ%): 277 ꢀ37.1), 275 ꢀM , 100.0), 146 ꢀ53.4); HRMS Found:
274.99969; C11H5ClF3NO2 requires: 274.99609.
‡
‡
ꢀC±F), 1114 ꢀC±O); MS m/z ꢀ%): 419ꢀM , 100.0); Analysis:
Found: C, 43.17; H, 2.55; N, 3.36%; C15H9 F8NO4 requires:
C, 42.97; H, 2.16; N, 3.34%.
3.1.5. Compound 4eg
1
Mp 99±1018C. H NMR ꢀCDCl3) d: 7.56±8.23 ꢀ4H, m,
ArH), 6.19 ꢀ1H, d, J ˆ 28:4 Hz, =CH) ppm; 19F NMR
ꢀCDCl3) d: 57.4 ꢀ2F, d, CF2Br), 106.1 ꢀ1F, m, =CF) ppm;
IR nmax ꢀcmÀ1): 1766 ꢀC=O), 1240 ꢀC±F), 1152 ꢀC±O); MS
3.1.10. Compound 4dh
1
Mp 125±1278C. H NMR ꢀCDCl3) d: 7.51 ꢀ1H, s, ArH),
7.03 ꢀ1H, s, ArH), 6.19 ꢀ1H, d, J ˆ 28:9 Hz, =CH), 4.01
ꢀ3H, s, OCH3), 3.99 ꢀ3H, s, OCH3) ppm; 19F NMR ꢀCDCl3)
d: 60.0 ꢀ2F, d, ClCF2), 108.1 ꢀ1F, m, =CF) ppm; IR nmax
ꢀcmÀ1):1736 ꢀC=O), 1274 ꢀC±F), 1140 ꢀC±F); MS m/z ꢀ%):
‡
m/z ꢀ%): 321 ꢀ26.4), 319 ꢀM , 26.8), 240 ꢀ100.0), 146 ꢀ17.0);
Analysis: Found: C, 41.68; H, 1.72; N, 4.36; C11H5BrF3NO2
requires: C, 41.28; H, 1.57; N, 4.38%.
‡
337 ꢀ34.1), 335 ꢀM , 100.0), 300 ꢀ18.1), 250 ꢀ22.0); HRMS
Found: 335.01842; C13H9ClF3NO4 requires: 335.01722.
3.1.6. Compound 4fg
Mp 97.0±98.58C. 1H NMR ꢀCDCl3) d: 7.56±8.23 ꢀ4H, m,
ArH), 6.27 ꢀ1H, d, JHF ˆ 29:2 Hz, =CH) ppm; 19F NMR
ꢀCDCl3) d: 71.08 ꢀ3F, s. CF3), 111.5 ꢀ1F, m, =CF) ppm; IR
nmax ꢀcmÀ1): 1758 ꢀC=O), 1601 ꢀC=N), 1258, 1211 ꢀC±F),
3.1.11. Compound 4eh
1
Mp 132±1338C. H NMR ꢀCDCl3) d: 7.50 ꢀ1H, s, ArH),
7.03 ꢀ1H, s, ArH), 6.19 ꢀ1H, d, J ˆ 28:8 Hz, =CH), 4.01
ꢀ3H, s, OCH3), 3.99 ꢀ3H, s, OCH3) ppm; 19F NMR ꢀCDCl3 )
d: 58.1 ꢀ2F, d, BrCF2), 109.3 ꢀ1F, m, =CF) ppm; IR nmax
‡
‡
1129 ꢀC±O); MS m/z ꢀ%): 259 ꢀM , 100.0), 240 ꢀM ±F, 5.9),
‡
‡
190 ꢀM ±CF3, 36.4), 146 ꢀM ±CF3CF=CH, 59.4); Analysis:

È
J.-T. Liu, H.-J. Lu / Journal of Fluorine Chemistry 111 ,2001) 213±216
216
ꢀcmÀ1): 1736 ꢀC=O), 1272 ꢀC±F), 1136 ꢀC±O); MS m/z ꢀ%):
381 ꢀ44.3), 379 ꢀM , 45.3), 300 ꢀ100.0); HRMS Found:
378.96643; C13H9BrF3NO4 requires: 378.96671.
3.1.18. Compound 4aj
‡
Mp 105±1078C. 1H NMR ꢀCDCl3) d: 8.33 ꢀ2H, dd,
J ˆ 2:1 Hz, ArH), 6.45 ꢀ1H, d, J ˆ 28:9 Hz, =CH) ppm;
19F NMR ꢀCDCl3 ) d: 80.3 ꢀ3F, t, CF3), 103.8 ꢀ1F, m, =CF),
118.0 ꢀ2F, m, CF2), 122.1 ꢀ4F, m, 2CF2), 125.6 ꢀ2F, m, CF2)
ppm; IR nmax ꢀcmÀ1):1770 ꢀC=O), 1238 ꢀC±F), 1138 ꢀC±O);
3.1.12. Compound 4fh
1
Mp 127±1288C. H NMR ꢀCDCl3) d: 7.52 ꢀ1H, s, ArH),
‡
7.03 ꢀ1H, s, ArH), 6.23 ꢀ1H, d, J ˆ 29:3 Hz, =CH), 4.02
ꢀ3H, s, OCH3), 4.00 ꢀ3H, s, OCH3) ppm; 19F NMR ꢀCDCl3 )
d: 72.8 ꢀ3F, s, CF3), 113.2 ꢀ1F, m, =CF) ppm; IR nmaxꢀcmÀ1):
1753 ꢀC=O), 1604 ꢀC=O), 1291, 1229 ꢀC±F), 1131 ꢀC±O);
MS m/z ꢀ%): 619 ꢀ50.0), 617 ꢀ100.0), 615 ꢀM , 53.2), 538
ꢀ9.7); HRMS Found: 614.83322; C15H3Br2F12NO2 requires:
614.83388.
‡
‡
MS m/z ꢀ%): 319 ꢀM , 100.0); 304ꢀM ±CH3, 20.9); HRMS
Found: 304.02159; C13H9F4NO4 requires: 304.02329.
3.1.19. Compound 4bj
Mp 97±988C. 1H NMR ꢀCDCl3) d: 8.40 ꢀ2H, dd,
J ˆ 2:1 Hz, ArH), 6.43 ꢀ1H, d, J ˆ 28:9 Hz, =CH) ppm;
19F NMR ꢀCDCl3) d: 66.8 ꢀ2F, t, ClCF2), 103.0 ꢀ1F, m, =CF),
116.8 ꢀ2F, m, CF2), 120.3 ꢀ2F, m, CF2) ppm; IR nmax ꢀcmÀ1):
1771 ꢀC=O), 1297 ꢀC±F), 1130 ꢀC±O); MS m/z ꢀ%): 537
3.1.13. Compound 4ai
Mp 120±1218C. 1H NMR ꢀCDCl3 ) d: 7.45±8.17 ꢀ3H, m,
ArH), 6.26 ꢀ1H, d, J ˆ 29:1 Hz, =CH) ppm; 19F NMR
ꢀCDCl3) d: 80.7 ꢀ3F, s, CF3), 105.2 ꢀ1F, m, =CF), 118.1
ꢀ2F, m, CF2), 122.4 ꢀ4F, m, 2CF2), 125.9 ꢀ2F, m, CF2) ppm;
IR nmax ꢀcmÀ1): 1760 ꢀC=O), 1253 ꢀC±F), 1140 ꢀC±O); MS
‡
ꢀ3.3), 535 ꢀ19.7), 533 ꢀ54.2), 531 ꢀM , 100.0); HRMS
Found: 530.80947; C13H3 Br2ClF7NO2 requires: 530.81072.
‡
m/z ꢀ%): 495 ꢀ34.2), 493 ꢀM , 100.0), 180 ꢀ30.2); HRMS
Found: 473.97743; C15H4ClF12NO2 requires: 473.97549.
3.1.20. Compound 4cj
Mp 101±1028C. 1H NMR ꢀCDCl3) d: 8.38 ꢀ2H, dd,
J ˆ 2:1 Hz, ArH), 6.50 ꢀ1H, d, J ˆ 28:9 Hz, =CH) ppm;
19F NMR ꢀCDCl3) d: 79.5 ꢀ3F, t, CF3),102.8 ꢀ1F, m, =CF),
118.3 ꢀ2F, m, CF2), 126.0 ꢀ2F, m, CF2) ppm; IR nmax ꢀcmÀ1):
1772 ꢀC=O), 1235 ꢀC±F),1126 ꢀC±O); MS m/z ꢀ%): 519
3.1.14. Compound 4bi
Mp 121±1238C. 1H NMR ꢀCDCl3) d: 7.53 ꢀ3H, m, ArH),
6.42 ꢀ1H, d, J ˆ 29:3 Hz, =CH) ppm; 19F NMR ꢀCDCl3 ) d:
66.8 ꢀ2F, t, ClCF2), 104.5 ꢀ1F, m, =CF), 116.8 ꢀ2F, m, CF2),
120.3 ꢀ2F, m, CF2) ppm; IR nmax ꢀcmÀ1): 1754 ꢀC=O), 1229
‡
ꢀ9.4), 517 ꢀ19.3), 515 ꢀM , 10.5), 241 ꢀ100.0); HRMS
Found: 514.84026; C13H3 Br2F8NO2 requires: 514.84027.
‡
ꢀC±F), 1145 ꢀC±O); MS m/z ꢀ%): 409 ꢀM , 5.5), 399 ꢀ80.4),
354 ꢀ100.0); HRMS Found: 408.94974, C13H4Cl2 F7NO4
requires: 408.95073.
3.1.21. Compound 5fh
1
Mp 135±1378C. H NMR ꢀCDCl3) d: 7.48 ꢀ1H, s, ArH),
6.97 ꢀ1H, s, ArH), 6.61 ꢀ1H, s, =CH), 3.99 ꢀ6H, s, 2OCH3),
2.47 ꢀ3H, s, COCH3) ppm; 19F NMR ꢀCDCl3) d: 72.2 ꢀ3F, s,
CF3) ppm; IR nmax ꢀcmÀ1): 1784, 1742 ꢀC=O), 1596 ꢀC=N),
3.1.15. Compound 4ci
1
Mp 119±1208C. H NMR ꢀCDCl3) d: 7.53±8.17 ꢀ3H, m,
‡
ArH), 6.30 ꢀ1H, d, J ˆ 29:1 Hz, =CH) ppm; 19F NMR
ꢀCDCl3 ) d: 80.3 ꢀ3F, t, CF3), 105.5 ꢀ1F, m, =CF), 119.0
ꢀ2F, m, CF2), 126.5 ꢀ2F, m, CF2) ppm; IR nmax ꢀcmÀ1): 1770
ꢀC=O), 1237 ꢀC±F), 1126 ꢀC±O); MS m/z ꢀ%): 395 ꢀ34.6),
1201 ꢀC±F), 1149 ꢀC±O); MS m/z ꢀ%): 359 ꢀM , 2.6),
‡
316 ꢀM ±CH3CO, 100.0); Analysis: Found: C, 50.39; H,
3.89; N, 3.85%; C15H12F3NO6 requires: C, 50.15; H, 4.21;
N, 3.90%.
‡
393 ꢀM , 100.0), 180 ꢀ34.7); HRMS Found: 373.98350;
C13H4ClF8NO2 requires: 373.98188.
Acknowledgements
3.1.16. Compound 4di
1
Mp 118±1198C. H NMR ꢀCDCl3) d: 7.52±8.16 ꢀ3H, m,
We thank the National Natural Science Foundation of
ChinaꢀNo.29772041and29902008)andShanghaiMunicipal
Scienti®c Committee ꢀNo. 00QA14030) for ®nancial support.
ArH),6.22ꢀ1H,d,J ˆ 29:2 Hz,=CH)ppm.19FNMRꢀCDCl3)
d:60.3ꢀ2F,d,CF2Cl),105.5ꢀ1F,m,=CF)ppm;IRnmaxꢀcmÀ1):
1755ꢀC=O),1284ꢀC±F),1147ꢀC±O);MSm/zꢀ%):313ꢀ11.3),
‡
311 ꢀ66.0), 309 ꢀM , 100.0), 180 ꢀ45.6); HRMS Found:
308.95349; C11H4Cl2F3NO2 requires: 308.94986.
References
[1] G.M. Coppola, J. Heterocycl. Chem. ꢀ1999) 563.
[2] T. Teshima, J.C. Griffin, J.C. Power, J. Biol. Chem. 257 ꢀ1982) 5085.
[3] R.L. Jarvest, M.J. Parratt, C.M. Debouck, J.G. Gorniak, L.J. Jennings,
H.T. Serafinowska, J.E. Strickler, Bioorg. Med. Chem. Lett. 6 ꢀ1996)
2463.
3.1.17. Compound 4ei
1
Mp 118±1198C. H NMR ꢀCDCl3) d: 7.51±8.15 ꢀ3H, m,
ArH), 6.22 ꢀ1H, d, J ˆ 28:5 Hz, =CH) ppm; 19F NMR
ꢀCDCl3) d: 56.8 ꢀ2F, d, ClCF2), 104.5 ꢀ1F, m, =CF) ppm;
IR nmax ꢀcmÀ1):1754 ꢀC=O), 1214 ꢀC±F), 1145 ꢀC±O); MS
m/z ꢀ%):357 ꢀ8.7), 355 ꢀ36.3), 353 ꢀM , 41.3), 274 ꢀ100.0);
Analysis: Found: C, 37.48; H, 1.42; N, 3.98%; C11H4BrCl
F3NO2 requires: C, 37.27; H, 1.14; N, 3.95%.
[4] P. Friedlaender, S. WleuÈgel, Chem. Ber. 16 ꢀ1883) 2229.
[5] B. Boutevin, R.L. Ranjalahy, A. Rousseau, J. Garapon, B. Sillion, J.
Fluorine Chem. 58 ꢀ1992) 29.
‡
[6] P. Goldman, Science 164 ꢀ1969) 1123.
[7] W.Y. Huang, L. LuÈ, Y. F. Zhang, Chin. J. Chem. ꢀ1990) 281.