An efficient preparation of N-per- (or poly)fluorophenyl pyrroles and N-fluoroalkanesulfonyl pyrroles

Article abstract of DOI:10.1016/j.tet.2003.09.078

Hetero-Diels-Alder reaction of N-sulfinyl per- (or poly)fluoroaniline and N-sulfinylfluoroalkanesulfonyl amine with 1,3-dienes affords the corresponding cycloadduct 3,6-dihydro-1,2-thiazine-1-oxide which is readily converted to N-per- (or poly)fluoropheny

Full text of DOI:10.1016/j.tet.2003.09.078

Tetrahedron 59 (2003) 9669–9676
An efficient preparation of N-per- (or poly)fluorophenyl pyrroles
and N-fluoroalkanesulfonyl pyrroles
a,b
Shizheng Zhu,a Xinyuan Liu and Shaowu Wangb
,
,
*
*
aShanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 354 Fenglin Lu, Shanghai 200032, China
bCollege of Chemistry and Materials Science, Anhui Normal University, Wuhu 241000, China
Received 28 April 2003; revised 15 September 2003; accepted 17 September 2003
Abstract—Hetero-Diels–Alder reaction of N-sulfinyl per- (or poly)fluoroaniline and N-sulfinylfluoroalkanesulfonyl amine with 1,3-dienes
affords the corresponding cycloadduct 3,6-dihydro-1,2-thiazine-1-oxide which is readily converted to N-per- (or poly)fluorophenyl pyrrole
and N-fluoroalkanesulfonyl pyrrole under mild reaction conditions in good yields.
q 2003 Elsevier Ltd. All rights reserved.
1. Introduction
cycloadducts 3,6-dihydro-1,2-thiazine-1-oxides are con-
verted to N-arylated pyrroles by base treatment12 or
photolysis.13
Pyrroles are important heterocycles broadly used in
materials science1 and found in naturally occurring and
biologically important molecules.2 Accordingly, substantial
attention has been paid to develop efficient methods for the
synthesis of pyrroles. Most known methods for the
construction of the pyrrole ring proceed via various types
of cycloaddition or cycloisomerization of acyclic precur-
sors.1–3 For example, Gevorgyan4 reported the Cu-assisted
cycloisomerization of alkynyl imines into the pyrrole ring,
while Ragaini5 found that under CO pressure and catalyzed
by (Pd(Phen)2)(BF4)2 the reaction of 1,3-diene with
nitroarenes afforded the oxazines which then eliminated
water on heating to give the corresponding N-arylpyrroles
(Scheme 1).
In this paper, we report an efficient two-step preparation of
N-per- (or poly) fluorophenyl pyrroles and N-fluoroalk-
anesulfonyl pyrroles: (1) (4þ2)-cycloaddition of N-sulfinyl
per- (or poly)fluoroanilines or N-sulfinylfluoroalkanesulfo-
nyl amines with 1,3-dienes. (2) Conversion of the
cycloadducts 3,6-dihydro-1,2-thiazine-1-oxides to N-per-
(or poly)fluorophenyl pyrroles or N-fluoroalkane- sulfonyl
pyrroles under basic reaction conditions.
2. Results and discussion
N-sulfinyl per- (or poly)fluoroanilines ArfNSO 1 or
N-sulfinylfluoroalkane sulfonyl amines RfSO2NSO 2 are
easily prepared by refluxing the per- (or poly) fluoroanilines
or fluoroalkanesulfonyl amides with an excess of sulfonyl
chloride. They are very reactive towards many organic
reagents such as aldehydes, alcohols, malonates, carboxylic
acids and acid anhydrides, etc. affording the condensation or
addition products.14–16
Moreover, most synthetic methods give the best results for
pyrroles bearing one or two substituents in the 2 and
5-position.6 Recently, we synthesized polyfunctionalized
3-fluoropyrroles from rhodium(II) acetate-catalyzed intra-
molecular N–H insertion reaction of d-amino-g,g-difluoro-
a-diazo-b-ketoesters (Scheme 2).7
To the best of our knowledge, there are no convenient
methods for the formation of N-fluorophenyl pyrroles. The
cycloaddition reactions of N-sulfinylanilines have attracted
major interest since they were first synthesized many
years ago.8–10 The N-sulfinylamino group (–NvSvO)
is an excellent reagent for (4þ2)-cycloadditions with
1,3-dienes8 – 10 and some derivatives also undergo
(2þ2)-cycloadditions with ynamines.11 These (4þ2)-
The thermal cycloaddition reaction of these new fluorine-
containing N-sulfinylamines with 1,3-dienes occurred
smoothly. For example, stirring of 1 with 2-methyl-1,3-
butadiene 3 or 2,3-dimethyl-1,3-butadiene 4 in a sealed tube
at 808C for 8 h gave the six-membered 2-(fluorophenyl)-3,6-
dihydro-1,2-thiazine-1-oxides in good yield (.80%)
(Scheme 3).
It was observed that the reactions of 1 with 3 gave two
isomers 5 and 6, which could not be separated by column
chromatography. According to the proton NMR spectra of
Keywords: Diels–Alder reaction; sulfinyl compound; 1,3-dienes; pyrrole.
*
Corresponding authors. Tel.: þ86-21-6416-3300; fax: þ86-21-6416-
6128; e-mail: zhusz@mail.sioc.ac.cn
0040–4020/$ - see front matter q 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2003.09.078

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S. Zhu et al. / Tetrahedron 59 (2003) 9669–9676
Scheme 1.
Scheme 2. (a) Ph3PvCHCN, toluene, 558C. (b) 1 mol% Rh2(OAc)4, toluene, reflux.
Scheme 3.
the mixed products, the 5-methyl substituted product 5 was
the major product. While 1e reacted with 3 afforded a
mixture of isomers 5e and 6e in a ratio of 1:1 (Table 1, entry
5). The 1H NMR spectra of all these cycloproducts 5, 6 and
7 showed the axial and equatorial protons of two cyclic
methylene groups. The axial and equatorial protons
appeared as two AB peaks with the 6-CH2 at the down
field. For example, 4,5-dimethyl-2-(4-chloro-tetrafluoro-
phenyl)-3,6-dihydro-1,2-thiazine-1-oxide 7b, DnAB¼311.7
Hz (for 6-CH2) and 165.6 Hz (for 3-CH2), the coupling
constant of the gem-protons for the 6-CH2 and 3-CH2 are
16.8 and 15.6 Hz, respectively. While several literature
works did not show clear AB peaks in their 1H NMR spectra
and reported as multiplets for the ring methylene groups.17,18
The molecular structure of the cylcloproduct 5c was
established by an X-ray crystallographic analysis (Fig. 1).
It is clear that the tetrafluorophenyl group is in the pseudo-
equatorial position and the oxygen atom is in the pseudo-
axial position. The six-membered ring adopts a more stable
chair conformation.19 An ordered pericyclic reaction
transition state is proposed for this Hetero-Diels–Alder
reaction and the stereochemistry of the products (Scheme 4).20
Table 1. Cycloaddition of N-per- (or poly)fluoroanilines with 1,3-dienes 3
or 4a
Entry
Reactant 1 (Arf)
3 or 4
Product and ratiob
Yield (%)c
Under basic reaction conditions compounds 5, 6 and 7
readily transformed the corresponding N-fluorophenyl
pyrroles in moderate to excellent yields (Scheme 5).
Generally, N-perfluorophenyl- or N-(4-chloro-tetrafluoro)
phenyl-3,6-dihydro-1,2-thiazine-1-oxide gave lower yield
(45–66%), while N-(monofluoro)phenyl- or N-(difluoro)-
1
2
3
4
5
6
C6F5(1a)
3
4
3
4
3
4
3
4
3
4
3
4
5a/6a (4:1)
7a
5b/6b (7:1)
7b
5c/6c (2:1)
7c
5d/6d (2:1)
7d
5e/6e (1:1)
7e
5f/6f (2:1)
7f0
80
83
97
99
99
97
88
100
95
93
100
96
4-ClC6F4(1b)
4-HC6F4(1c)
2,4-F2C6H3(1d)
3,4-ClFC6H3(1e)
2-FC6H4(1f)
a
Reaction was carried out in a sealed tube at 808C using CH2Cl2 as a
solvent.
b
c
The ratio of product 5/6 based on the 1H NMR spectra.
Isolated yield.
Scheme 4.

S. Zhu et al. / Tetrahedron 59 (2003) 9669–9676
9671
Figure 1. X-Ray crystal structure of 5c.
Table 2. Preparation of N-per (or poly) pyrroles 8 and 9
Entry Reactant 5, 6 or 7 Reaction conditiona Product Yield (%)b
1
2
3
4
5
6
7
8
5a, 6a
7a
5b, 6b
7b
5c, 6c
7c
5d, 6d
7d
5e, 6e
7e
5f, 6f
7f
508C, 8 h
508C, 8 h
8a
9a
8b
9b
8c
9c
8d
9d
8e
9e
8f
55
50
66
45
57
70
67
80
64
88
71
91
508C, 12 h
508C, 12 h
508C, 12 h
508C, 12 h
608C, 24 h
608C, 24 h
608C, 24 h
608C, 24 h
608C, 24 h
608C, 24 h
Scheme 5.
phenyl-3,6-dihydro-1,2-thiazine-1-oxide gave higher yields
(Table 2).
9
10
11
12
In the process for the formation of pyrroles, Et3N should
either act as a base abstracting the 6-hydrogen or as a
nucleophile attracking the sulfur atom and then caused the
ring opening followed by the elimination of ‘HSOH’ to
afford N-fluoro-phenyl pyrroles (Scheme 6).17,21
9f
a
All reactions were carried out in MeOH.
Isolated yield.
b
498, it is very similar to N-pentafluorophenyl aromatic
aldimine C6F5NvCHPh, in which the angle between the
phenyl and pentafluorophenyl planes is 49.28.17 XRD
analysis of compound 8a showed the existence of the
intermolecular hydrogen bonds between the fluorine atom
of the pentafluorophenyl and the hydrogen atom of the
These N-fluorophenyl pyrroles are fully characterized
spectroscopically and some are further elucidated by
X-ray crystallographic analysis. Figure 2 shows the X-ray
crystal structure of compound 8a. The bond lengths of
˚
N–C6, N–C7 and N–C10 are 1.408, 1.378 and 1.381 A,
˚
pyrrole ring, the distance of H· · ·F is 2.496 A and the angle
respectively; all are shorter than normal nitrogen–carbon
single bond indicating its conjugated property. However, it
was shown that the pentafluorophenyl plane and the pyrrole
plane are not coplanar, the angle between the two planes is
of C1–F1· · ·H is 148.418. The packing map (Fig. 3) shows
that the pentafluorophenyl plane in one molecule is parallel
and just overlaps with the pyrrole planes in the other
Scheme 6.

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S. Zhu et al. / Tetrahedron 59 (2003) 9669–9676
Figure 2. X-Ray crystal structure of 8a.
Figure 3. The packing map of 8a.
two molecules, the pyrrole plane also lies between the two
pentafluorophenyl planes. The distance between the two
˚
parallel planes is 3.47 A. These alternate overlapped
molecules suggest some interaction between the p-electron
˚
systems. The average volume per non-H atom is 15.2 A. On
the crude products with Et3N and P(OEt)3 in methanol gave
expected N-fluoroalkanesulfonyl pyrroles 11 in about 60–
65% yield. Products 11 are stable and can be further purified
by fractional column distillation (Scheme 7).
the basis of the above fact, it may be concluded that the
molecular packing in the cell is very dense.
In conclusion, we have demonstrated a concise and efficient
synthetic route to N-fluorophenyl pyrroles or N-fluoroalkane-
sulfonyl pyrroles from readily available starting compounds
N-sulfinyl fluoroanilines or N-sulfinylfluoroalkane sulfonyl
amines by two reaction steps. Further chemical transform-
ation of these fluorine-containing pyrroles is under
investigation.
Under similar reaction conditions, N-sulfinylfluoroalkane-
sulfonyl amines RfSO2NSO 2 could also react with 1,3-
1
butadiene 10. The H NMR spectra of the crude products
showed only two unsaturated proton at 5.78 and 5.69 ppm,
indicating the cycloaddition products was formed. How-
ever, an attempt to purify the product by distillation or
column chromatography failed. It was found that during the
column chromatography on silica gel the six-membered ring
opened to give an inseparable mixture. While fractional
column distillation of the crude products gave mainly the
corresponding fluoroalkanesulfonyl amides RfSO2NH2. The
easy decomposition of N-fluoroalkanesulfonyl 3,6-dihydro-
1,2-thiazine-1-oxides may be attributed to the strong
electron-withdrawing ability of RfSO2 group. Treatment of
3. Experimental
Melting points were measured in Temp-Melt apparatus and
were uncorrected. 1H, 13C and 19F NMR spectra were
recorded in CDCl3 on Bruker AM-300 instruments with
Me4Si and CFCl3 (with upfield negative) as the internal and
external standards, respectively. IR spectra were obtained
with a Nicolet AV-360 spectrophotometer. Low resolution
Scheme 7.

S. Zhu et al. / Tetrahedron 59 (2003) 9669–9676
9673
mass spectrum or high resolution mass spectra (HRMS)
were obtained on a Finnigan GC–MS 4021 or a Finnigan
MAT-8430 instrument using the electron impact ionization
technique (70 eV), respectively. Elemental analyses were
performed by this Institute. X-Ray crystallographic struc-
ture analysis was performed on a Bruker P4 instrument.
Dichloromethane was distilled from CaH2 and reagents
were purified before use. N-sulfinyl per- (or poly)fluoroa-
nilines and N-sulfinylfluoroalkanesulfonyl amines were
prepared as previous described.14,22
(2F, d, J¼13.8 Hz), 2144.89 (2F, d, J¼14.9 Hz). MS: m/z
(%) 315 (Mþþ2, 1), 313 (Mþ, 2), 185 (2), 183 (6), 68 (100),
67 (36), 53 (12). Anal. calcd for C11H8ClF4NOS: C, 42.12;
H, 2.57; N, 4.46. Found: C, 42.29; H, 2.54; N, 4.34.
3.1.5. 5-Methyl-2-(2,3,5,6-tetrafluorophenyl)-3,6-dihy-
dro-1,2-thiazine-1-oxide (5c) and 4-methyl-2-(2,3,5,6-
tetrafluorophenyl)-3,6-dihydro-1,2-thiazine-1-oxide
(6c). Colorless crystals, mp: 121–1228C. IR (KBr) cm21
:
3041, 1640, 1503, 1478, 1186, 1154, 1145, 1080. 1H NMR
(CDCl3) d 1.61 (1H, s, 4-CH3), 1.92 (2H, s, 5-CH3), 3.20
(AB, JAB¼15.9 Hz, 1H, 3-Ha), 3.63 (AB, JAB¼16.8 Hz,
1H, 6-Ha), 3.72 (AB, JAB¼15.9 Hz, 1H, 3-Hb), 4.58 (AB,
JAB¼16.8 Hz, 1H, 6-Hb), 5.79 (1H, s, 4,5-H), 6.98–7.04
(1H, m, Ar). 19F NMR (CDCl3) d 2138.30 (2F, m),
2146.07 (2F, m). MS: m/z (%) 279 (Mþ, 3), 211 (11), 149
(13), 68 (100), 67 (52), 53 (13). Anal. calcd for
C11H9F4NOS: C, 47.31; H, 3.25; N, 5.02. Found: C,
47.30; H, 3.33; N, 4.91.
3.1. General procedure for the reaction of N-sulfinyl per-
(or poly)fluoroanilines (1) with 1,3-dienes (3) or (4)
3.1.1. 2-(4-Chloro-tetrafluorophenyl)-4,5-dimethyl-3,6-
dihydro-1,2-thiazine-1-oxide (7b). A solution of N-sulfinyl-
(4-chloro-tetrafluoro)aniline 1b (0.49 g, 2.00 mmol) and 2,3-
dimethyl-1,3-butadiene 4 (2.5 mmol) in dry CH2Cl2 (5.0 mL)
was placed in a sealed tube, and stirred at 808C for 8 h. The
solvent was removed in vacuo, the residue was purified on
silica gel using ethyl acetate/hexane (v/v, 1:8) as the elutent to
give a white solid product 7b, which was further recrystallized
from dichloromethane/hexane (v/v, 1:1) to give the pure
product 7b (0.65 g, 1.98 mmol, 99%) as colorless crystals.
Mp: 122–1248C. IR (KBr) cm21: 2920, 2857, 1496, 1158,
1077. 1HNMR(CDCl3) d1.78(3H, s, CH3), 1.84(3H, s, CH3),
3.19 (AB, JAB¼15.6 Hz, 1H, 3-Ha), 3.42 (AB, JAB¼15.9 Hz,
1H, 6-Ha), 3.75 (AB, JAB¼16.2 Hz, 1H, 3-Hb), 4.46 (AB,
JAB¼16.8 Hz, 1H, 6-Hb). 19F NMR (CDCl3) d 2140.42 (2F,
d, J¼13.8 Hz), 2144.77 (2F, d, J¼15.5 Hz). 13C NMR
(CDCl3) d 17.0, 19.8, 47.2, 54.8, 104.3, 115.2, 124.3, 125.0,
143.4 (d, 1JC–F¼167.6 Hz), 146.8 (d, 1JC–F¼156.9 Hz). MS:
m/z (%) 327 (Mþ, 11), 82 (100). Anal. calcd for C12H10ClF4-
NOS: C, 43.99; H, 3.08; N, 4.28. Found: C, 43.94; H, 2.98; N,
4.04.
3.1.6. 4,5-Dimethyl-2-(2,3,5,6-tetrafluorophenyl)-3,6-
dihydro-1,2-thiazine-1-oxide (7c). Colorless crystals, mp:
104–1068C. IR (KBr) cm21: 3025, 2926, 1510–1449,
1
1194–1037. H NMR (CDCl3) d 1.78 (3H, s, CH3), 1.84
(3H, s, CH3), 3.19 (AB, JAB¼15.6 Hz, 1H, 3-Ha), 3.45 (AB,
JAB¼15.9 Hz, 1H, 6-Ha), 3.75 (AB, JAB¼16.2 Hz, 1H,
3-Hb), 4.49 (AB, JAB¼15.9 Hz, 1H, 6-Hb), 6.95–7.07 (1H,
m, Ar). 19F NMR (CDCl3) d 2138.35 (2F, m), 2145.93 (2F,
m). MS: m/z (%) 293 (Mþ, 5), 211 (2), 149 (13), 82 (100), 67
(61). Anal. calcd for C12H11F4NOS: C, 49.16; H, 3.78; N,
4.78. Found: C, 49.11; H, 3.66; N, 4.59.
3.1.7. 5-Methyl-2-(2,4-difluorophenyl)-3,6-dihydro-1,2-
thiazine-1-oxide (5d) and 4-methyl-2-(2,4-difluorophe-
nyl)-3,6-dihydro-1,2-thiazine-1-oxide (6d). Yellow oil. IR
(KBr) cm21: 2915, 1598, 1505, 1432, 1296, 1145, 1145, 1084.
1H NMR (CDCl3) d 1.84 (1H, s, 4-CH3), 1.88 (2H, s, 5-CH3),
3.16 (AB, JAB¼16.2 Hz, 1H, 3-Ha), 3.61 (AB, JAB¼16.5 Hz,
1H, 6-Ha), 3.72 (AB, JAB¼16.2 Hz, 1H, 3-Hb), 4.26 (AB,
JAB¼16.5 Hz, 1H, 6-Hb), 5.52 (0.33H, s, 5-H), 5.77 (0.66H, s,
4-H), 6.85–6.92 (2H, m, Ar), 7.36–7.75 (1H, m, Ar). 19F
NMR (CDCl3) d 2111.14 (1F, m), 2117.69 (1F, m). MS: m/z
(%) 243 (Mþ, 12), 175 (26), 113 (24), 68 (100), 67 (41), 53
(14). Anal. calcdforC11H11F2NOS: C, 54.31;H, 4.56;N, 5.76.
Found: C, 54.48; H, 4.96; N, 5.63.
3.1.2. 5-Methyl-2-(pentafluorophenyl)-3,6-dihydro-1,2-
thiazine-1-oxide (5a) and 4-methyl-2-(pentafluorophe-
nyl)-3,6-dihydro-1,2-thiazine-1-oxide (6a). Colorless
crystals, mp: 65–688C. IR (KBr) cm21: 2945, 1520, 1396,
1380, 1185, 1096, 1033, 988. 1H NMR (CDCl3) d 1.57 (0.6H,
s, 4-CH3), 1.91 (2.4H, s, 5-CH3), 3.20 (AB, JAB¼16.2 Hz, 1H,
3-Ha), 3.57 (AB, JAB¼17.1 Hz, 1H, 6-Ha), 3.71 (AB,
JAB¼16.2 Hz, 1H, 3-Hb), 4.52 (AB, JAB¼17.1 Hz, 1H, 6-
Hb), 5.77 (1H, s, 4,5-H). 19F NMR (CDCl3) d 2145.06 (2F, d,
J¼16.6 Hz), 2155.15 (1F, t, J¼21.4 Hz), 2161.40 (2F, m).
MS:m/z(%)297(Mþ, 15),229(3), 167(20), 68(100), 67(42),
53 (12). Anal. calcd for C11H8F5NOS: C, 44.45; H, 2.71; N,
4.71. Found: C, 44.52; H, 2.63; N, 4.57.
3.1.8. 4,5-Dimethyl-2-(2,4-difluorophenyl)-3,6-dihydro-
1,2-thiazine-1-oxide (7d). Colorless crystals, mp: 92–
948C. IR (KBr) cm21: 3033, 2926, 1505, 1438, 1430,
1
1269, 1220, 1147, 1112, 1076. H NMR (CDCl3) d 1.77
3.1.3. 4,5-Dimethyl-2-(pentafluorphenyl)-3,6-dihydro-
1,2-thiazine-1-oxide (7a). Colorless crystals, mp: 57–
588C. Lit.23 57–588C.
(3H, s, CH3), 1.83 (3H, s, CH3) 3.15 (AB, JAB¼16.5 Hz, 1H,
3-Ha), 3.43 (AB, JAB¼16.2 Hz, 1H, 6-Ha), 3.74 (AB,
JAB¼16.2 Hz, 1H, 3-Hb), 4.16 (AB, JAB¼15.9 Hz, 1H, 6-
Hb), 6.84–6.92 (2H, m, Ar), 7.39–7.47 (1H, m, Ar). 19F
NMR(CDCl3) d 2111.23 (1F, m), 2117.77 (1F, m). MS: m/
z (%) 257 (Mþ, 34), 175 (11), 113 (25), 82 (100), 67 (67).
Anal. calcd for C12H13F2NOS: C, 56.02; H, 5.09; N, 5.44.
Found: C, 55.99; H, 4.91; N, 5.25.
3.1.4. 5-Methyl-2-(4-chloro-tetrafluorophenyl)-3,6-dihy-
dro-1,2-thiazine-1-oxide (5b) and 4-methyl-2-(4-chloro-
tetrafluorophenyl)-3,6-dihydro-1,2-thiazine-1-oxide
(6b). Colorless crystals, mp: 134–1368C. IR (KBr) cm21
:
2905, 1482, 1161, 1088. 1H NMR (CDCl3) d 1.59 (0.37H, s,
4-CH3), 1.88 (2.63H, s, 5-CH3), 3.20 (AB, JAB¼16.2 Hz,
1H, 3-Ha), 3.62 (AB, JAB¼16.5 Hz, 1H, 6-Ha), 3.71 (AB,
JAB¼16.2 Hz, 1H, 3-Hb), 4.56 (AB, JAB¼16.5 Hz, 1H,
6-Hb), 5.79 (1H, s, 4,5-H). 19F NMR (CDCl3) d 2140.35
3.1.9. 5-Methyl-2-(3-chloro-4-fluorophenyl)-3,6-dihy-
dro-1,2-thiazine-1-oxide (5e) and 4-methyl-2-(3-chloro-
4-fluorophenyl)-3,6-dihydro-1,2-thiazine-1-oxide (6e).
Colorless crystals, mp:104–1068C. IR (KBr) cm21: 2914,

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S. Zhu et al. / Tetrahedron 59 (2003) 9669–9676
1504, 1232, 1066. 1H NMR (CDCl3) d 1.57 (1.5H, s, 4-H),
1.88 (1.5H, s, 5-CH3), 3.20 (AB, JAB¼15.9 Hz, 1H, 3-Ha),
3.49 (AB, JAB¼16.8 Hz, 1H, 6-Ha), 3.65 (AB,
JAB¼15.9 Hz, 1H, 3-Hb), 4.13 (AB, JAB¼16.8 Hz, 1H,
6-Hb), 5.53 (0.5H, s, 5-H), 5.79 (0.5H, s, 4-H), 7.07–7.28
(3H, m, Ar). 19F NMR (CDCl3) d 2119.61 (1F, m). MS: m/z
(%) 261 (Mþþ2, 9), 259 (Mþ, 23), 193 (10), 191 (26), 156
(42), 131 (11), 129 (33), 68 (100), 67 (34), 53 (9). Anal.
calcd for C11H11ClFNOS: C, 50.87; H, 4.27; N, 5.39.
Found: C, 50.89; H, 4.15; N, 5.19.
was further recrystallized from hexane to give the pure
product 9b (0.12 g, 45%) as colorless crystals.
3.2.1. 1-(4-Chloro-tetrafluorophenyl)-3,4-dimethylpyr-
role (9b). Colorless crystals, mp: 100–1028C. IR
1
(KBr) cm21: 3080, 2948, 1537, 1499, 1157, 976. H NMR
(CDCl3) d 2.06 (6H, s, CH3), 6.65 (2H, s, 2,5-H). 19F
NMR(CDCl3) d 2140.53 (2F, d, J¼15.5 Hz), 2149.14 (2F,
d, J¼14.4 Hz). 13C NMR (CDCl3) d 10.06, 119.54, 119.62,
1
119.66, 121.48, 141.44 (d, JC–F¼246.7 Hz), 144.74 (d,
1JC–F¼248.21 Hz). MS: m/z (%) 279 (Mþþ2, 25), 278
(Mþþ1, 42), 277 (Mþ, 76), 276 (Mþ21, 100), 264 (4), 262
(11), 67 (10). Anal. calcd for C12H8ClF4N: C, 51.91; H,
2.90; N, 5.04. Found: C, 51.78; H, 2.79; N, 4.89.
3.1.10. 4,5-Dimethyl-2-(3-chloro-4-flurophenyl)-3,6-
dihydro-1,2-thiazine-1-oxide (7e). Colorless crystals, mp:
174–1758C. IR (KBr) cm21: 2935, 2903, 1584, 1506, 1238,
1
1062. H NMR (CDCl3) d 1.81 (3H, s, CH3), 1.83 (3H, s,
CH3), 3.20 (AB, JAB¼16.2 Hz, 1H, 3-Ha), 3.48 (AB,
JAB¼15.9 Hz, 1H, 6-Ha), 3.68 (AB, JAB¼16.2 Hz, 1H,
3-Hb), 4.14 (AB, JAB¼15.9 Hz, 1H, 6-Hb), 7.08–7.28 (3H,
m, Ar). 19F NMR (CDCl3) d 2119.82 (1F, m). MS: m/z (%)
275 (Mþþ2, 3), 273 (Mþ, 7), 212 (2), 210 (6), 131 (5),
129 (14), 82 (100), 67 (52). Anal. calcd for C12H13ClFNOS:
C, 52.65; H, 4.79; N, 5.12. Found: C, 52.61; H, 4.65; N,
5.02.
3.2.2. 1-(Pentafluorophenyl)-3-methylpyrrole (8a). Col-
orless crystals, mp: 73–748C. IR (KBr) cm21: 3140, 2953,
2932, 1515, 1305, 1242, 1065, 987. H NMR (CDCl3) d
2.17 (3H, s, CH3), 6.25–6.26 (1H, m, 4-H), 6.65 (1H, s, 2-
H), 6.77–6.80 (1H, m, 5-H). 19F NMR (CDCl3) d: 2149.62
(2F, d, J¼16.9 Hz), 2157.54 (1F, t, J¼17.8 Hz), 2161.75
(2F, t, J¼21.3 Hz). MS: m/z (%) 248 (Mþþ1, 10), 247 (Mþ,
87), 246 (Mþ21, 100), 167 (10), 53 (7). Anal. calcd for
C11H6F5N: C, 53.45; H, 2.45; N, 5.67. Found: C, 53.42; H,
2.56; N, 5.58.
1
3.1.11. 5-Methyl-2-(2-fluorophenyl)-3,6-dihydro-1,2-
thiazine-1-oxide (5f) and 4-methyl-2-(2-fluorophenyl)-
3,6-dihydro-1,2-thiazine-1-oxide (6f). Yellow oil. IR
(KBr) cm21: 2914, 1498, 1449, 1259, 1084. 1H NMR
(CDCl3) d 1.85 (1H, s, 4-CH3), 1.88 (2H, s, 5-CH3), 3.15
(AB, JAB¼16.1 Hz, 1H, 3-Ha), 3.67 (AB, JAB¼16.2 Hz,
1H, 6-Ha), 3.73 (AB, JAB¼16.1 Hz, 1H, 3-Hb), 4.29 (AB,
JAB¼16.2 Hz, 1H, 6-Hb), 5.52 (0.33H, s, 5-H), 5.78 (0.66H,
s, 4-H), 7.07–7.41 (4H, m, Ar). 19F NMR (CDCl3) d
2122.73 (1F, m). MS: m/z (%) 225 (Mþ, 43), 157 (53), 95
(43), 68 (100), 67 (47), 53 (15). Anal. calcd for
C11H12FNOS: C, 58.65; H, 5.37; N, 6.22. Found: C,
58.41; H, 5.30; N, 6.17.
3.2.3. 1-(Pentafluorophenyl)-3,4-dimethylpyrrole (9a).
Colorless crystals, mp: 91–928C. Lit.23 91–928C.
3.2.4. 1-(4-Chloro-tetrafluorophenyl)-3-methylpyrrole
(8b). Colorless crystals, mp: 59–608C. IR (KBr) cm21
:
1
3146, 2930, 1524, 1499, 1154, 975. H NMR (CDCl3) d
2.17 (3H, s, CH3), 6.25–6.26 (1H, m, 4-H), 6.70 (1H, m,
5-H), 6.82–6.85 (1H, m, 2-H). 19F NMR (CDCl3) d:
2140.61 (2F, d, J¼15.2 Hz), 2149.13 (2F, d, J¼14.4 Hz).
MS: m/z (%) 265 (Mþþ2, 29), 264 (Mþþ1, 43), 263 (Mþ,
91), 262 (Mþ21, 100), 185 (3), 183 (7), 53 (27). Anal. calcd
for C11H6ClF4N: C, 50.12; H, 2.29; N, 5.31. Found: C,
50.22; H, 2.27; N, 5.31.
3.1.12. 4,5-Dimethyl-2-(2-fluorophenyl)-3,6-dihydro-1,2-
thiazine-1-oxide (7f). Colorless crystals, mp: 81–868C. IR
(KBr) cm21: 2914, 2824, 1609, 1499, 1454, 1440, 1203,
3.2.5. 1-(2,3,5,6-Tetrafluorophenyl)-3-methylpyrrole
(8c). Colorless crystals, mp: 51–528C. IR (KBr) cm21
:
1
1120, 1075. H NMR (CDCl3) d 1.78 (3H, s, CH3), 1.83
1
(3H, s, CH3), 3.15 (AB, JAB¼16.2 Hz, 1H, 3-Ha), 3.48 (AB,
JAB¼16.2 Hz, 1H, 6-Ha), 3.75 (AB, JAB¼16.2 Hz, 1H,
3-Hb), 4.20 (AB, JAB¼16.2 Hz, 1H, 6-Hb), 7.07–7.45 (4H,
m, Ar). 19F NMR(CDCl3) d 2122.82 (1F, m). MS: m/z (%)
239 (Mþ, 12), 157 (5), 95 (20), 82 (100), 67 (70). Anal.
calcd for C12H14FNOS: C, 60.23; H, 5.90; N, 5.85. Found:
C, 60.23; H, 5.94; N, 5.75.
3099, 2927, 1517, 1174, 1144, 939. H NMR (CDCl3) d
2.16 (3H, s, CH3), 6.23–6.24 (1H, m, 4-H), 6.70–6.72 (1H,
m, 5-H), 6.83–6.86 (1H, m, 2-H), 6.95–7.06 (1H, m, Ar).
19F NMR (CDCl3) d 2138.21 (2F, m), 2149.90 (2F, m).
MS: m/z (%) 230 (Mþþ1, 10), 229 (Mþ, 77), 228 (Mþ21,
100), 149 (9), 53 (8). HRMS (m/z) calcd for C11H7F4N[Mþ],
229.0501, found 229.0515.
3.2. General procedure for preparation of N-per- (or
poly)fluorophenyl pyrroles 8 and 9
3.2.6. 1-(2,3,5,6-Tetrafluorophenyl)-3,4-dimethylpyrrole
(9c). Colorless crystals, mp: 72–738C. IR (KBr) cm21
:
1
3089, 2944, 2927, 1646, 1514, 1174, 1141, 937. H NMR
(CDCl3) d 2.07 (6H, s, CH3), 6.67 (2H, s, 2,5-H), 6.91–7.02
(1H, m, Ar). 19F NMR (CDCl3) d: 2138.38 (2F, m),
2150.23 (2F, m). MS: m/z (%) 244 (Mþþ1, 12), 243 (Mþ,
91), 242 (Mþ21, 100), 228 (12), 149 (9), 67 (10). Anal.
calcd for C12H9F4N: C, 59.26; H, 3.73; N, 5.76. Found: C,
59.25; H, 3.71; N, 5.61.
The dihydrothiazine oxide 7b (0.33 g, 1 mmol) was added
to a stirring solution containing triethylamine (0.07 mL,
0.05 g, 0.5 mmol), triethyl phosphite (0.26 mL, 0.25 g,
1.5 mmol) and methanol (10 mL). The mixture was stirred
at 608C overnight. Then the reaction solvent was removed in
vacuo. The residue was treated with hydrochloric acid (1N,
12 mL) and then was extracted with ether (10 mL£3). The
organic layer was washed with water, dried over MgSO4 and
concentrated in vacuo. Flash column chromatography on
silica gel, eluting with hexane afforded the product, which
3.2.7. 1-(2,4-Difluorophenyl)-3-methylpyrrole (8d). Col-
orless oil. IR (KBr) cm21: 3095, 2925, 1522, 1439,
1
1270, 1144, 971. H NMR (CDCl3) d 2.16 (3H, s, CH3),

S. Zhu et al. / Tetrahedron 59 (2003) 9669–9676
9675
6.17–6.19 (1H, m, 4-H), 6.73–6.74 (1H, m, 5-H), 6.85–
7.00 (3H, m, 2-H and Ar), 7.27–7.35 (1H, m, Ar). 19F NMR
(CDCl3) d 2112.92 (1F, m), 2120.67 (1F, m). MS: m/z (%)
194 (Mþþ1, 10), 193 (Mþ, 85), 192 (Mþ21, 100), 113 (14),
53 (11). HRMS (m/z) calcd for C11H9F2N [Mþ2CH3],
178.0456, found 178.0468.
Table 3. X-Ray data collection and processing parameters for compounds
5c and 8a
Compound
5c (CCDC 215664)
8a (CCDC 215665)
Formula
C
11H9F4NOS
C11H6F5N
0.22£0.31£0.27
P2 (1)/C
Monoclinic
6.148(1)
7.762(1)
21.141(4)
90.00
94.70(3)
90.00
1005.5(3)
4
1.633
0.162
293(2)
4–55
3340
496
2294
0.0339
1282
Size (mm)
Space group
Crystal system
0.51£0.26£0.24
P-1
Triclinic
5.960(0)
9.612(1)
10.822(1)
110.630(2)
105.298(2)
82.126(2)
559.08(12)
2
1.659
0.330
293(2)
4–56
3438
284
2483
0.0248
1954
199
0.953
0.0401; 0.0901
0.0502; 0.0939
3.2.8. 1-(2,4-Difluorophenyl)-3,4-dimethylpyrrole (9d).
Colorless crystals, mp: 33–348C. IR (KBr) cm21: 3084,
2926, 1535, 1516, 1142, 969. 1H NMR (CDCl3) d 2.06 (6H,
s, CH3), 6.70 (2H, s, 2,5-H), 6.86–6.98 (2H, m, Ar), 7.24–
7.31 (1H, m, Ar). 19F NMR (CDCl3) d 2113.72 (1F, m),
2120.95 (1F, m). MS: m/z (%) 208 (Mþþ1, 10), 207 (Mþ,
79), 206 (Mþ21, 100), 192 (12), 113 (7). Anal. calcd for
C12H11F2N: C, 69.55; H, 5.35; N, 6.76. Found: C, 69.77; H,
5.51; N, 6.53.
˚
a (A)
˚
b (A)
˚
c (A)
a (8)
b (8)
g (8)
3
˚
V (A )
Z-value
Dcalc (g cm23
)
m (mm21
T (K)
2u range (8)
)
3.2.9. 1-(3-Chloro-4-fluorophenyl)-3-methylpyrrole (8e).
Colorless crystals, mp: 47–488C. IR (KBr) cm21: 3117,
Total reflections
F(000)
Independent reflections
Rint
I.2s(I)
1
2924, 1509, 1262, 1239, 1069. H NMR (CDCl3) d 2.15
(3H, s, CH3), 6.17–6.18 (1H, m, 4-H), 6.78 (1H, s, 2-H),
6.89–6.91 (1H, m, 5-H), 7.16–7.20 (2H, m, Ar), 7.37–7.40
(1H, m, Ar). 19F NMR (CDCl3) d 2120.35 (1F, m). MS: m/z
(%) 211 (Mþþ2, 25), 210 (Mþþ1, 42), 209 (Mþ, 75), 208
(Mþ21, 100), 131 (4), 129 (11), 53 (7). Anal. calcd for
C11H9ClFN: C, 63.02; H, 4.33; N, 6.68. Found: C, 62.84; H,
4.28; N, 6.72.
Parameters
157
1.014
0.0541; 0.1380
0.1043; 0.1684
Goodness of fit
Final R indices (I.2s(I))
R indices (all data)
m/z (%) 383 (Mþþ2, 31), 381 (Mþ, 58), 137 (16), 135 (52),
130 (5), 116 (100), 114 (27), 87 (8), 85 (27), 66 (75). Anal.
calcd for C8H4ClF8NO3S: C, 25.18; H, 1.06; N, 3.67; F,
39.83. Found: C, 25.42; H, 0.98; N, 4.07; F, 39.95.
3.2.10. 1-(3-Chloro-4-fluorophenyl)-3,4-dimethylpyrrole
(9e). Colorless crystals, mp: 38–408C. IR (KBr) cm21
:
3095, 2924, 2859, 1531, 1504, 1260, 1216, 1069, 1046. 1H
NMR (CDCl3) d 2.06 (6H, s, CH3), 6.74 (2H, s, 2,5-H),
7.13–7.16 (2H, m, Ar), 7.33–7.36 (1H, m, Ar). 19F NMR
(CDCl3) d 2121.22 (1F, m). MS: m/z (%) 225 (Mþþ2, 24),
224 (Mþþ1, 42), 223 (Mþ, 73), 222 (Mþ21, 100), 208 (9),
131 (4), 129 (11), 67 (7). Anal. calcd for C12H11ClFN: C,
64.44; H, 4.96; N, 6.26. Found: C, 64.30; H, 5.12; N, 5.99.
3.2.14. 1-[(5-Iodo-3-oxa-octafluoropentyl)sulfonyl]-pyr-
role (11b). Colorless oil. IR (KBr) cm21: 3153, 1463,
1
1422, 1336, 1296, 1196–1142, 1060. H NMR (CDCl3) d
6.50 (2H, m), 7.20 (2H, m). 19F NMR (CDCl3) d 265.25
(2F, m, ICF2), 281.61 (2F, m, CF2O), 285.52 (2F, m,
OCF2), 2114.89 (2F, s, CF2S). MS: m/z (%) 473 (Mþ, 100),
227 (56), 177 (43), 116 (66), 114 (28), 66 (98). Anal. calcd
for C8H4F8INO3S: C, 20.31; H, 0.85; N, 2.96. Found: C,
20.28; H, 0.99; N, 3.14.
3.2.11. 1-(2-Fluorophenyl)-3-methylpyrrole (8f). Color-
less oil. IR (KBr) cm21: 3071, 2923, 1614, 1515, 1352,
1
1231. H NMR (CDCl3) d 2.17 (3H, s, CH3), 6.18–6.19
(1H, m, 4-H), 6.81–6.82 (1H, m, 5-H), 6.93–6.95 (1H, m,
2-H), 7.13–7.21 (3H, m, Ar), 7.31–7.37 (1H, m, Ar). 19F
NMR (CDCl3) d 2125.19 (1F, m). MS: m/z (%) 176
(Mþþ1, 11), 175 (Mþ, 85), 174 (Mþ21, 100), 95 (13), 53
(11). Anal. calcd for C11H10FN: C, 75.41; H, 5.75; N, 7.99.
Found: C, 75.07; H, 5.63; N, 8.36.
3.3. X-Ray crystal structure data of compounds (5c) and
(8a)
Intensity data were collected at 293(2) K on Bruker P4
diffractometer with graphite monochromator and Mo Ka
˚
radiation (l¼0.71073 A). The structure was solved by
3.2.12. 1-(2-Fluorophenyl)-3,4-dimethylpyrrole (9f). Col-
orless oil. IR (KBr) cm21: 3050, 2924, 1533, 1508, 1400,
direct methods and explained using Fourier techniques. The
nonhydrogen atoms were refined anisotropically, hydrogen
atoms were included but not refined. The final cycle of full
matrix least-squares refinement was based on F 2, respect-
ively. All calculations were performed using SHELXS-97
and SHELXL-97 programs. X-Ray data for compounds 5c
and 8a are listed in Table 3.
1
1365, 1108, 1053. H NMR (CDCl3) d 2.11 (6H, s, CH3),
6.82 (2H, s, 2,5-H), 7.16–7.37 (4H, m, Ar). 19F NMR
(CDCl3) d 2125.77 (1F, s). MS: m/z (%) 190 (Mþþ1, 11),
189 (Mþ, 81), 188 (Mþ21, 100), 174 (12), 95 (14), 67 (9).
Anal. calcd for C12H12FN: C, 76.17; H, 6.39; N, 7.40.
Found: C, 76.00; H, 6.37; N, 7.73.
3.2.13. 1-[(5-Chloro-3-oxa-octafluoropentyl)sulfonyl]-
pyrrole (11a). Colorless oil, bp: 76–788C/266 Pa. IR
(KBr) cm21: 3180, 1590, 1560, 1430, 1310, 1230–1140,
Acknowledgements
The authors thank the National Natural Science Foundation
of China (NNSFC) (No. 20032010, No. 20072049, No.
20072001) and Excellent Yong Scholars Foundation of
Anhui Province.
1
1060. H NMR (CDCl3) d 6.30 (2H, m), 7.00 (2H, m). 19F
NMR (CDCl3) d 274.81 (2F, s, ClCF2), 282.32 (2F, m,
CF2O), 287.34 (2F, m, OCF2), 2117.82 (2F, s, CF2S). MS:

9676
S. Zhu et al. / Tetrahedron 59 (2003) 9669–9676
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