Optically active 4-aryl-4-trifluoromethyl-4H-1,3-oxa(thia)zines

Article abstract of DOI:10.1016/j.jfluchem.2009.09.010

S(-)-4-Aryl-4-(N-acylamino)-5,5,5-trifluoropentan-2-ones have been reacted with phosphorus pentachloride and pentasulfide to yield S(-)-4-aryl-4-trifluoromethyl-4H-1,3-oxazines and S(+)-4-aryl-4-trifluoromethyl-4H-1,3-thiazines, respectively.

Full text of DOI:10.1016/j.jfluchem.2009.09.010

Journal of Fluorine Chemistry 131 (2010) 229–233
Contents lists available at ScienceDirect
Journal of Fluorine Chemistry
journal homepage: www.elsevier.com/locate/fluor
Optically active 4-aryl-4-trifluoromethyl-4H-1,3-oxa(thia)zines
*
Mykhaylo V. Vovk , Nataliya M. Golovach, Volodymyr A. Sukach
Institute of Organic Chemistry, National Academy of Sciences of Ukraine, Murmans’ka 5, Kyiv 02094, Ukraine
A R T I C L E I N F O
A B S T R A C T
Article history:
S(À)-4-Aryl-4-(N-acylamino)-5,5,5-trifluoropentan-2-ones have been reacted with phosphorus pen-
tachloride and pentasulfide to yield S(À)-4-aryl-4-trifluoromethyl-4H-1,3-oxazines and S(+)-4-aryl-4-
trifluoromethyl-4H-1,3-thiazines, respectively.
Received 30 July 2009
Received in revised form 16 September 2009
Accepted 18 September 2009
Available online 28 September 2009
ß 2009 Elsevier B.V. All rights reserved.
Keywords:
Optically active compounds
b-Aminoketones
4H-1,3-oxazines
4H-1,3-thiazines
Trifluoromethyl group
1. Introduction
2. Results and discussion
Monocyclic 1,3-oxazines [1,2] and 1,3-thiazines [3] attract
much interest both as versatile synthons in heterocyclic chemistry
and as compounds with manifold biological activities. Although
the synthetic approaches to various 4H-1,3-oxa(thia)zines have
been thoroughly developed, there is still little evidence about their
trifluoromethyl-substituted derivatives [4,5]. Among a few known
Compounds 1a–h are readily obtained in 80–87% yields by
acylation of 4-amino-4-aryl-5,5,5-trifluoropentan-2-ones [10]
with acetic anhydride or aroyl chlorides (Table 1). We have found
that compounds 1b, e, g, h are less reactive than N-3-oxoalk-
ylamides [11,12] towards PCl5 and produce S(À)-4-aryl-4-trifluor-
omethyl-4H-1,3-oxazines 2a–d (Table 2) only on 8 h boiling in
benzene. The reaction is likely to involve the intermediate
formation of imidoyl chlorides A which undergo intramolecular
cyclization.
As previously established [13], thionation of N-3-oxoalkyla-
mides with P2S5 gives only traces of the corresponding 4H-1,3-
thiazines. We have succeeded in developing appropriate condi-
tions to efficiently convert amides 1a–h into S(+)-4-aryl-4-
trifluoromethyl-4H-1,3-thiazines 3a–h (Table 3). Boiling reagents
for 18–20 h in xylene with a 10-fold excess of P2S5 affords 75–83%
yield of desired products. Interestingly, widely used Lawesson’s
reagent [14] failed to provide a higher than 15–20% degree of
thionation in the reaction concerned.
Formation of thiazines 3 is a multistep process which probably
starts with the thionation of carbonyl groups (intermediate B)
followed by thermal cyclocondensation (cyclic intermediate C) and
finally by hydrogen sulfide elimination. Conversion of amides 1
into oxazines 2 and thiazines 3 does not involve the chiral carbon
centre so that the absolute configuration of reagents is retained in
target compounds, practically without loss in optical purity (as
evidenced by 19F NMR spectroscopy using tris[3-(heptafluorobu-
tyryl)-L-camphorato]europium(III) as a chiral lanthanide shift
reagent).
examples
are
4,4-bis(perfluoroalkyl)-4H-1,3-oxa(thia)zines
obtained by cycloaddition of perfluoroalkyl ketone N-acylimines
to ketenes and alkenes [6] or alkynes [7]. If performed with
hexafluoroacetone N-thioacylimines and phenylacetylene, this
reaction provides 4,5-dihydrothiazoles as by-products along with
expected 4,4-bis(trifluoromethyl)-4H-1,3-thiazines [8].
Recently we have shown that chiral
b-trifluoromethyl-b-
aminoketones can be successfully applied in the synthesis of
optically active heterocycles containing a quaternary endocyclic
chiral centre, e.g., 4-trifluoromethyl-substituted 3,4-dihydropyr-
imidin-2(1H)-(thi)ones and 3,4-dihydro-1,3-oxazin-2-ones [9].
Here we report a synthetic method for new optically active 4-
trifluoromethyl derivatives of 1,3-oxa(thia)zines based on a very
facile cyclocondensation of easily available chiral S(À)-N-[1-aryl-
3-oxo-1-(trifluoromethyl)butyl]amides 1a–h with phosphorus
pentachloride or pentasulfide.
* Corresponding author. Fax: +380 44 5732643.
E-mail address: mvovk@i.com.ua (M.V. Vovk).
0022-1139/$ – see front matter ß 2009 Elsevier B.V. All rights reserved.
doi:10.1016/j.jfluchem.2009.09.010

230
M.V. Vovk et al. / Journal of Fluorine Chemistry 131 (2010) 229–233
19F) as internal standards. Compounds were identified by TLC on
Table 1
(
Analytical data of compounds 1.
Silufol-254 plates using a mixture of hexane:ethylacetate as
eluent. Elemental analysis was performed in the Analytical
Laboratory of the Institute of Organic Chemistry, National
Academy of Sciences of Ukraine.
Compound
Ar
R
Yield (%)a
Mp (8C)b
Ee (%)
1a
1b
1c
1d
1e
1f
Ph
Me
85
86
88
84
85
80
87
85
127–130
121–123
216–218
130–132
110–112
115–117
232–234
110–112
75
76
76
79
78
70
70
72
Ph
Ph
Ph
4-BrC6H4
Me
4-FC6H4
4-FC6H4
4-MeC6H4
4-MeC6H4
4-MeOC6H4
3.1. S(À)-N-[1-Aryl-3-oxo-1-(trifluoromethyl)butyl]acetamides (1a,
d, f, h) and S(À)-N-[1-aryl-3-oxo-1-
Ph
Me
(trifluoromethyl)butyl]benzamides (1b, c, e, g)
1g
1h
4-NO2C6H4
Me
To a solution of 4-amino-4-aryl-5,5,5-trifluoropentan-2-one
(0.5 g, 2.16 mmol) in dry toluene (6 ml), acetic anhydride (0.44 g,
4.32 mmol) or the corresponding (un)substituted benzoyl chloride
(4.32 mmol) was added to obtain compounds 1a, d, f, h or 1b, c, e, g,
respectively. The reaction mixture was boiled for 4 h, followed by
evaporation of the solvent. The oily residue was recrystallized from
hexane.
a
Yields of isolated products.
b
Melting points are uncorrected.
Table 2
Analytical data of compounds 2.
Compound
Ar
R
Yield (%)a
Ee (%)
2a
2b
2c
2d
2e
Ph
Ph
Ph
77
73
75
73
70
74
75
68
70
74
3.2. S(À)-N-[3-Oxo-1-phenyl-1-(trifluoromethyl)butyl]acetamide
(1a)
4-FC6H4
4-MeC6H4
4-MeC6H4
4-MeOC6H4
4-NO2C6H4
Me
Me
[a
]
D
20 = À45.98 (c = 0.47; MeOH). IR (KBr)
y: 1695, 1755 (C55O),
a
3315 (N–H). 1H NMR
d: 2.07 (s, 3H), 2.18 (s, 3H), 3.44 (d, 1H,
Yields of isolated products.
J = 17.0 Hz), 3.82 (d, 1H, J = 17.0 Hz), 6.58 (s, 1H), 7.37–7.46 (m,
5Harom.). 19F NMR (CDCl3)
d
: À75.29. 13C NMR
d: 24.14 (CH3), 31.51
Table 3
Analytical data of compounds 3.
(CH3), 43.45 (CH2), 63.07 (q, J = 27.6 Hz), 126.02, 127.52 (q, CF3,
J = 286.7 Hz), 128.64, 128.68, 135.92 (Carom.), 170.25 (C55O), 203.89
(C55O). Anal. calculated for C13H14F3NO2: C, 67.14; H, 5.16; N,
5.13%. Found: C, 67.96; H, 5.24; N, 5.28%.
Compound
Ar
R
Yield (%)a
Ee (%)
3a
3b
3c
3d
3e
3f
Ph
Me
78
83
82
80
77
83
78
75
73
72
72
74
70
73
69
71
Ph
Ph
Ph
4-BrC6H4
Me
3.3. S(À)-N-[1-(4-Fluorophenyl)-3-oxo-1-
(trifluoromethyl)butyl]acetamide (1d)
4-FC6H4
4-FC6H4
4-MeC6H4
4-MeC6H4
4-MeOC6H4
Ph
Me
[a
]
D
20 = À9.90 (c = 1.01; MeOH). IR (KBr)
y: 1695, 1750 (C55O),
3g
3h
4-NO2C6H4
Me
3315 (N–H). 1H NMR
d: 2.09 (s, 3H), 2.19 (s, 3H), 3.41 (d, 1H,
J = 16.8 Hz), 3.71 (d, 1H, J = 16.8 Hz), 6.64 (s, 1H), 7.08 (t, 2Harom.
,
a
Yields of isolated products.
J = 8.7 Hz), 7.40–7.44 (m, 2Harom.). 19F NMR (CDCl3)
d
: À75.59,
To conclude, we have used the easily accessible N-acyl
derivatives of optically active 4-amino-4-aryl-5,5,5-trifluoropen-
tan-2-ones to synthesize new chiral trifluoromethyl-substituted
1,3-azines, viz., S-4-aryl-4-trifluoromethyl-4H-1,3-oxa(thia)zines.
À114.54. 13C NMR
d: 24.03 (CH3), 31.57 (CH3), 43.44 (CH2), 62.94
(q, J = 27.6 Hz), 115.55 (d, J = 21.3 Hz), 125.12 (q, CF3, J = 286.7 Hz),
128.07 (d, J = 7.5 Hz), 131.78, 162.6 (d, J = 247.9 Hz), 170.35 (C55O),
203.73 (C55O). Anal. calculated for C13H13F4NO2: C, 53.61; H, 4.50;
N, 4.81%. Found: C, 53.98; H, 5.07; N, 4.97%.
3. Experimental
3.4. S(À)-N-[1-(4-Methylphenyl)-3-oxo-1-
(trifluoromethyl)butyl]acetamide (1f)
IR spectra were recorded on a UR-20 instrument in KBr disks for
compounds 1a–h and in CH2Cl2 solutions for compounds 2a–e and
3a–h. 1H, 13C, and 19F NMR spectra were measured in CDCl3 on a
Bruker Avance DRX-500 spectrometer at the respective frequen-
cies 500.13, 125.75 and 470.59 MHz using TMS (1H, 13C) and CCl3F
[
a
]
20 = À25.00 (c = 1.0; MeOH). IR (KBr)
y: 1715, 1745 (C55O),
D
3430 (N–H). 1H NMR
d: 2.07 (s, 3H), 2.17 (s, 3H), 2.34 (s, 3H), 3.42
(d, 1H, J = 16.8 Hz), 3.81 (d, 1H, J = 16.8 Hz), 6.42 (s, 1H), 7.21 (d,

M.V. Vovk et al. / Journal of Fluorine Chemistry 131 (2010) 229–233
231
2Harom., J = 8.1 Hz), 7.30 (d, 2Harom., J = 8.1 Hz). 19F NMR
13C NMR
: 20.96 (CH3), 24.14 (CH3), 31.44 (CH3), 43.31 (CH2),
63.08 (q, J = 27.6 Hz), 125.91, 125.27 (q, CF3, J = 286.7 Hz), 129.36,
132.94, 138.56 (Carom.), 170.28 (C55O), 203.86 (C55O). Anal.
calculated for C14H16F3NO2: C, 58.53; H, 5.61; N, 4.88%. Found:
C, 58.82; H, 5.97; N, 5.06%.
d
: À75.59.
(CH3), 32.05 (CH3), 44.46 (CH2), 64.02 (q, J = 27.6 Hz), 123.97,
125.32 (q, CF3, J = 287.9 Hz), 125.59, 128.43, 129.67, 132.43,
138.88, 139.91, 149.89 (Carom.), 164.83 (C55O), 205.51 (C55O). Anal.
calculated for C19H17F3N2O4: C, 57.87; H, 4.35; N, 7.10%. Found: C,
58.04; H, 4.85; N, 7.62%.
d
3.10. S(À)-4-Aryl-6-methyl-4-trifluoromethyl-4H-1,3-oxazines
(2a–e)
3.5. S(À)-N-[1-(4-Methoxyphenyl)-3-oxo-1-
(trifluoromethyl)butyl]acetamide (1h)
To a solution of amide 1b, e, f, g, h (1 mmol) in dry benzene
(10 ml), phosphorus pentachloride (0.23 g, 1.1 mmol) was added
and the reaction mixture was boiled for 8 h. After evaporation of
the solvent, dichloromethane (15 ml) and a concentrated K2CO3
solution (15 ml) were added to the residue, followed by stirring for
10 min. The organic layer was separated, washed with water, and
dried over Na2SO4. Filtration and evaporation then afforded
analytically pure oily products.
[
a
]
20 = À16.12 (c = 0.62; MeOH). IR (KBr)
y: 1710, 1721 (C55O),
D
3365 (N55H). 1H NMR
d: 2.10 (s, 3H), 2.19 (s, 3H), 3.43 (d, 1H,
J = 16.5 Hz), 3.83–3.86 (m, 4H), 6.38 (s, 1H), 6.94 (d, 2Harom.
J = 8.5 Hz), 7.36 (d, 2Harom., J = 8.1 Hz). 19F NMR
: 24.19 (CH3), 31.48 (CH3), 43.26 (CH2), 55.27 (CH3O), 62.91 (q,
J = 27.6 Hz), 113.99, 125.28 (q, CF3, J = 286.7 Hz), 127.35, 127.78,
159.65 (Carom.), 170.27 (C55O), 203.87 (C55O). Anal. calculated for
,
d
: À75.81. 13C NMR
d
C14H16F3NO3: C, 55.44; H, 5.32; N, 4.62%. Found: C, 56.92; H, 5.77;
N, 4.81%.
3.11. S(À)-2,6-Diphenyl-6-methyl-4-trifluoromethyl-4H-1,3-oxazine
(2a)
3.6. S(À)-N-[3-Oxo-1-phenyl-1-(trifluoromethyl)butyl]benzamide
(1b)
Oil. [
a
]
20 = À223.40 (c = 0.47; MeOH). IR (CH2Cl2)
y: 1725
D
(C55N). 1H NMR
d: 2.06 (s, 3H), 5.38 (s, 1H), 7.28–7.55 (m, 6Harom.),
[
a
]
20 = À39.36 (c = 0.65; MeOH). IR (KBr)
y
: 1695, 1718 (C55O),
7.70 (d, 2Harom., J = 7.0 Hz), 8.18 (d, 2Harom., J = 7.0 Hz). 19F NMR
d:
D
3375 (N–H). 1H NMR
d
: 2.20 (s, 3H), 3.45 (d, 1H, J = 16.5 Hz), 3.75
À79.69. 13C NMR
d
: 18.80 (CH3), 62.09 (q, C4, J = 28.9 Hz), 96.15
(d, 1H, J = 16.5 Hz), 7.38–7.57 (m, 9Harom.), 7.85–7.87 (m, 2Harom.).
(C5), 125.85 (q, CF3, J = 284.1 Hz), 126.72, 127.82, 128.18, 128.30,
128.34, 131.47, 131.64, 140.65 (Carom.), 131.43, 153.59. Anal.
calculated for C18H14F3NO: C, 68.13; H, 4.45; N, 4.41%. Found: C,
68.85; H, 4.97; N, 4.83%.
19F NMR
d
: À73.55. 13C NMR
d: 31.84 (CH3), 44.71 (CH2), 63.87 (q,
J = 27.6 Hz), 125.44 (q, CF3, J = 287.9 Hz), 125.88, 127.18, 128.69,
128.78, 128.80, 132.01, 134.37, 136.00 (Carom.), 166.88 (C55O),
204.84 (C55O). Anal. calculated for C18H16F3NO2: C, 64.47; H, 4.81;
N, 4.18%. Found: C, 64.63; H, 5.13; N, 4.45%.
3.12. S(À)-4-(4-Fluorophenyl)-6-methyl-2-phenyl-4-
trifluoromethyl-4H-1,3-oxazine (2b)
3.7. S(À)-N-[1-(4-Bromophenyl)-3-oxo-1-
(trifluoromethyl)butyl]benzamide (1c)
Oil. [
a
]
20 = À136.14 (c = 0.63; MeOH). IR (CH2Cl2)
y: 1725
D
(C55N). 1H NMR
d: 2.07 (s, 3H), 5.34 (s, 1H), 7.09–7.10 (m, 2Harom.),
[
a
]
20 = À45.68 (c = 0.74; MeOH). IR (KBr)
y
: 1710, 1730
7.50–7.53 (m, 3Harom.), 7.63–7.64 (m, 2Harom.), 8.16–8.17 (m,
2Harom.). 19F NMR
D
(C55O), 3370 (N–H). 1H NMR
d
: 2.22 (s, 3H), 3.40 (d, 1H, J = 18 Hz),
d
: À80.03, À115.28. 13C NMR
d: 18.79 (CH3),
3.69 (d, 1H, J = 18 Hz), 7.38–7.46 (m, 5Harom.), 7.60 (s, 1H), 7.62 (d,
2Harom., J = 9.0 Hz), 7.71 (d, 2Harom., J = 9.0 Hz). 19F NMR
: À73.27.
13C NMR
: 31.93, 44.73, 63.91 (q, J = 27.5 Hz), 125.51 (q, CF3,
61.68 (q, C4, J = 28.9 Hz), 95.86 (C5), 115.10, 115.27, 125.64, 125.83
(q, CF3, J = 284.4 Hz), 127.81, 128.32, 128.58, 131.31, 131.75
(Carom.), 149.28, 153.74, 162.51 (d, J = 247.7 Hz). Anal. calculated
for C18H13F4NO: C, 64.48; H, 3.91; N, 4.18%. Found: C, 64.96; H,
4.33; N, 4.47%.
d
d
J = 287.2 Hz), 125.78, 126.79, 128.82, 128.84, 128.88, 132.00,
133.19, 135.82 (Carom.), 165.90, 205.13. Anal. calculated for
C
18H15BrF3NO2: C, 52.19; H, 3.65; N, 3.38%. Found: C, 52.25; H,
3.62; N, 3.37%.
3.13. S(À)-6-Methyl-4-(4-methylphenyl)-2-(4-nitrophenyl)-4-
trifluoromethyl-4H-1,3-oxazine (2c)
3.8. S(À)-N-[1-(4-Fluorophenyl)-3-oxo-1-
(trifluoromethyl)butyl]benzamide (1e)
Oil. [
a
]
20 = À217.10 (c = 0.76; MeOH). IR (CH2Cl2)
y: 1720
D
(C55N). 1H NMR
d: 2.08 (s, 3H), 2.38 (s, 3H), 5.40 (s, 1H), 7.24 (d,
[
a
]
20 = À55.56 (c = 0.45; MeOH). IR (KBr)
y
: 1715, 1735 (C55O),
2Harom., J = 8.5 Hz), 8.18 (d, 2Harom., J = 8.5 Hz), 8.31–8.32 (m,
4Harom.). 19F NMR
J = 28.9 Hz), 96.15 (C5), 125.85 (q, CF3, J = 284.1 Hz), 126.72, 127.82,
128.18, 128.30, 128.34, 131.47, 131.64, 140.65 (Carom.), 131.43,
153.59. Anal. calculated for C19H15F3N2O3: C, 60.64; H, 4.02; N,
7.44%. Found: C, 61.18; H, 4.55; N, 7.53%.
D
3365 (N–H). 1H NMR
d
: 2.22 (s, 3H), 3.42 (d, 1H, J = 16.5 Hz), 3.67
d
: À79.71. 13C NMR
d
: 18.80 (CH3), 62.09 (q, C4,
(d, 1H, J = 16.5 Hz), 7.10 (t, 2Harom., J = 8.4 Hz), 7.45–7.56 (m,
6Harom.), 7.85–7.87 (m, 2Harom.). 19F NMR
NMR
d
: À73.84, À114.49. 13
C
d
: 31.91 (CH3), 44.74 (CH2), 63.56 (q, J = 27.6 Hz), 115.75 (d,
J = 22.6 Hz), 125.34 (q, CF3, J = 286.7 Hz), 127.18, 127.89, 127.95,
128.79, 132.15, 134.12, 162.60 (d, J = 248.9 Hz), 166.93 (C55O),
204.76 (C55O). Anal. calculated for C18H15F4NO2: C, 61.19; H, 4.28;
N, 3.96%. Found: C, 61.97; H, 4.85; N, 4.04%.
3.14. S(À)-2,6-Dimethyl-4-(4-methylphenyl)-4-trifluoromethyl-4H-
1,3-oxazine (2d)
3.9. S(À)-N-[1-(4-Methylphenyl)-3-oxo-1-(trifluoromethyl)butyl]-4-
nitrobenzamide (1g)
Oil. [
a
d
]
20 = À30.61 (c = 9.8; MeOH). IR (CH2Cl2)
y: 1725 (C55N).
D
1H NMR
: 1.86 (s, 3H), 2.13 (s, 3H), 2.34 (s, 3H), 5.19 (s, 1H), 7.19 (d,
2Harom., J = 8.1 Hz), 7.48 (d, 2Harom., J = 8.1 Hz). 19F NMR
d
: À78.20.
[a
]
D
20 = À44.55 (c = 0.10; MeOH). IR (KBr)
y
: 1705, 1720 (C55O),
13C NMR : 18.67 (CH3), 20.94 (CH3), 55.28 (CH3), 61.45 (q, C4,
d
3345 (N–H). 1H NMR
d
: 2.21 (s, 3H), 2.35 (s, 3H), 3.39 (d, 1H,
J = 28.9 Hz), 95.77 (C5), 124.54 (q, CF3, J = 284.1 Hz), 125.67, 126.50,
J = 17.0 Hz), 3.72 (d, 1H, J = 17.0 Hz), 7.22 (d, 2Harom., J = 7.0 Hz),
7.36 (d, 2Harom., J = 7.0 Hz), 7.50 (s, 1H), 7.60 (d, 2Harom., J = 6.5 Hz),
129.04, 129.41 (Carom.), 148.64, 156.22. Anal. calculated for
C14H14F3NO: C, 62.45; H, 5.24; N, 5.20%. Found: C, 62.98; H,
7.72 (d, 2Harom., J = 6.5 Hz). 19F NMR
d
: À73.74. 13C NMR
d: 21.02
5.87; N, 5.67%.

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M.V. Vovk et al. / Journal of Fluorine Chemistry 131 (2010) 229–233
3.15. S(À)-2,6-Dimethyl-4-(4-methoxyphenyl)-4-trifluoromethyl-
4H-1,3-oxazine (2e)
C, 53.97; H, 3.83; N, 4.84; S 11.08%. Found: C, 54.12; H, 4.03; N,
4.93; S, 11.23%.
Oil. [
a
]
20 = À48.60 (c = 0.72; MeOH). IR (CH2Cl2)
y
: 1725
3.21. S(+)-4-(4-Fluorophenyl)-6-methyl-2-phenyl-4-
D
(C55N). 1H NMR
d
: 1.88 (s, 3H), 2.14 (s, 3H), 3.80 (s, 3H), 5.19 (s, 1H),
trifluoromethyl-4H-1,3-thiazine (3e)
6.91 (d, 2Harom., J = 8.7 Hz), 7.48 (d, 2Harom., J = 8.7 Hz). 19F NMR
d:
À79.83. 13C NMR
d
: 18.66 (CH3), 20.91 (CH3), 55.28 (CH3), 61.44 (q,
Oil. [
a
]
20 = +34.03 (c = 0.89; MeOH). IR (CH2Cl2)
y
: 1690
D
C4, J = 28.9 Hz), 95.76 (C5), 113.69, 124.53 (q, CF3, J = 284.1 Hz),
(C55N). 1H NMR
d: 2.28 (s, 3H), 6.16 (s, 1H), 7.04–7.11 (m, 2Harom.),
127.90, 132.37, 148.62 (Carom.), 156.40, 159.36. Anal. calculated for
14H14F3NO2: C, 58.95; H, 4.95; N, 4.91%. Found: C, 61.18; H, 4.55;
N, 4.98%.
7.54–7.62 (m, 5Harom.), 8.05 (d, 2Harom., J = 8.0 Hz). 19F NMR
d:
C
À78.34 (3F), À113.73 (1F). 13C NMR
d
: 22.01 (CH3), 69.65 (q, C4,
J = 27.6 Hz), 114.57 (C5), 115.24 (d, J = 21.4 Hz), 123.91 (q, CF3,
J = 282.9 Hz), 128.25, 129.04, 129.92, 132.40, 132.60, 133.10
(Carom.), 134.60, 134.88, 162.94 (d, J = 248.9 Hz). Anal. calculated
for C18H13F4NS: C, 61.53; H, 3.73; N, 3.99; S, 9.13%. Found: C, 61.94;
H, 4.14; N, 4.17; S, 9.54%.
3.16. S(+)-4-Aryl-6-methyl-4-trifluoromethyl-4H-1,3-thiazines
(3a–h)
To a solution of amide 1a–h (1 mmol) in dry xylene (15 ml),
phosphorus pentasulfide (0.22 g, 10 mmol) was added and the
reaction mixture was boiled with vigorous stirring for 18–20 h.
After cooling, the organic layer was decanted and the solvent was
evaporated to give analytically pure oily products.
3.22. S(+)-2,6-Dimethyl-4-(4-methylphenyl)-4-trifluoromethyl-4H-
1,3-thiazine (3f)
Oil. [
1H NMR
2Harom., J = 7.8 Hz), 7.34 (d, 2Harom., J = 7.8 Hz). 19F NMR
a
d
]
20 = +28.76 (c = 1.0; MeOH). IR (CH2Cl2)
y
: 1695 (C55N).
: 2.15 (s, 3H), 2.33 (s, 3H), 2.67 (s, 3H), 5.99 (s, 1H), 7.19 (d,
: À77.06.
D
3.17. S(+)-2,6-Dimethyl-4-phenyl-4-trifluoromethyl-4H-1,3-thiazine
d
(3a)
13C NMR : 21.19 (CH3), 21.70 (CH3), 26.37 (CH3), 68.78 (q, C4,
d
J = 27.6 Hz), 113.88 (C5), 123.23, 126.51 (q, CF3, J = 284.2 Hz),
Oil. [
(C55N). 1H NMR
(m, 5Harom.). 19F NMR
(CH3), 69.58 (q, C4, J = 28.8 Hz), 113.26 (C5), 124.73 (q, CF3,
J = 284.1 Hz), 127.81, 127.53, 128.24, 128.97 (Carom.), 131.43,
136.8. Anal. calculated for C13H12F3NS: C, 57.55; H, 4.46; N,
5.16; S, 11.82%. Found: C, 58.02; H, 4.97; N, 5.34; S, 11.98%.
a
]
20 = +20.62 (c = 0.97; MeOH). IR (CH2Cl2)
y
: 1690
127.58, 129.31, 132.79(Carom.), 130.83, 131.11. Anal. calculated for
C14H14F3NS: C, 58.93; H, 4.95; N, 4.91; S, 11.24%. Found: C, 59.17;
H, 5.43; N, 4.98; S, 11.76%.
D
d
: 2.12 (s, 3H), 2.55 (s, 3H), 6.01 (s, 1H), 7.33–7.46
d
: À77.88. 13C NMR
d
: 21.87 (CH3), 26.70
3.23. S(+)-6-Methyl-4-(4-methylphenyl)-2-(4-nitrophenyl)-4-
trifluoromethyl-4H-1,3-thiazine (3g)
Oil. [
a
d
]
20 = +34.40 (c = 1.0; MeOH). IR (CH2Cl2)
y
: 1690 (C55N).
D
3.18. S(+)-2,4-Diphenyl-6-methyl-4-trifluoromethyl-4H-1,3-thiazine
1H NMR
: 2.20 (s, 3H), 2.31 (s, 3H), 6.13 (s, 1H), 7.11 (d, 2Harom.,
(3b)
J = 7.8 Hz), 7.34 (d, 2Harom., J = 7.8 Hz), 7.61 (d, 2Harom., J = 8.7 Hz),
7.89 (d, 2Harom., J = 8.7 Hz). 19F NMR
d
: À78.61. 13C NMR
d: 21.15
Oil. [
(C55N). 1H NMR
a
]
D
20 = +23.48 (c = 0.75; MeOH). IR (CH2Cl2)
y
: 1695
(CH3), 22.14 (CH3), 70.38 (q, C4, J = 27.6 Hz), 114.29 (C5), 126.73 (q,
CF3, J = 284.2 Hz), 127.80, 128.65, 129.11, 131.84, 132.08, 134.32,
134.68, 135.51, 138.57, 159.86 (Carom.). Anal. calculated for
d
: 2.24 (s, 3H), 6.15 (s, 1H), 7.32–7.34 (m, 3Harom.),
7.47–7.60 (m, 5Harom.), 8.02 (d, 2Harom., J = 7.0 Hz). 19F NMR
d:
À78.63. 13C NMR
d
:
d
21.98 (CH3), 70.13 (q, C4, J = 27.6 Hz), 114.87
C19H15F3N2O2S: C, 58.16; H, 3.85; N, 7.14; S, 8.17%. Found: C,
58.73; H, 4.02; N, 7.56; S, 8.75%.
(C5), 124.98 (q, CF3, J = 282.9 Hz), 127.99, 128.22, 128.32, 128.93,
129.01, 129.11, 132.11, 133.07(Carom.), 134.91, 136.62. Anal.
calculated for C18H14F3NS: C, 64.85; H, 4.23; N, 4.20; S 9.62%.
Found: C, 64.98; H, 4.83; N, 4.66; S, 9.77%.
3.24. S(+)-2,6-Dimethyl-4-(4-methoxyphenyl)-4-trifluoromethyl-
4H-1,3-thiazine (3h)
3.19. S(+)-2-(4-Bromphenyl)-6-methyl-4-phenyl-4-trifluoromethyl-
Oil. [
a
]
20 = +14.86 (c = 0.95; MeOH). IR (CH2Cl2)
y
: 1695
D
4H-1,3-thiazine (3c)
(C55N). 1H NMR
d: 2.19 (s, 3H), 2.91 (s, 3H), 3.81 (s, 3H), 5.98 (s, 1H),
6.98 (d, 2Harom., J = 8.7 Hz), 7.43 (d, 2Harom., J = 8.7 Hz). 19F NMR
d:
Oil. [
a
]
20 = +40.93 (c = 0.50; MeOH). IR (CH2Cl2)
y
: 1690
À76.79. 13C NMR
d: 21.60 (CCH3), 29.72 (CH3), 55.45 (CH3O), 68.58
D
(C55N). 1H NMR
d
: 2.22 (s, 3H), 6.17 (s, 1H), 7.32–7.34 (m, 3Harom.),
(q, C4, J = 27.6 Hz), 114.26 (C5), 126.38 (q, CF3, J = 284.2 Hz), 126.92,
7.50–7.51 (m, 2Harom.), 7.62 (d, 2Harom., J = 8.0 Hz), 7.93 (d, 2Harom.
,
128.94, 129.10, 132.15, 143.70, 160.40 (Carom.). Anal. calculated for
C14H14F3NOS: C, 55.80; H, 4.68; N, 4.65; S, 10.65%. Found: C, 55.99;
H, 4.97; N, 4.77; S, 10.92%.
J = 8.0 Hz). 19F NMR
d
: À78.47. 13C NMR
d
: 22.16 (CH3), 69.71 (q, C4,
J = 27.6 Hz), 114.25 (C5), 127.50 (q, CF3, J = 284.2 Hz), 126.63,
127.98, 128.78, 129.20, 131.05, 131.93, 132.28, 135.33 (Carom.),
137.36, 160.54. Anal. calculated for C18H13BrF3NS: C, 52.44; H,
3.18; N, 3.40; S, 7.78%. Found: C, 52.87; H, 4.97; N, 3.58; S, 7.97%.
References
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3.20. S(+)-2,6-Dimethyl-4-(4-fluorophenyl)-4-trifluoromethyl-4H-
1,3-thiazine (3d)
Oil. [
a
]
20 = +10.03 (c = 0.50; MeOH). IR (CH2Cl2)
y
: 1690
D
(C55N). 1H NMR
d
: 2.18 (s, 3H), 2.73 (s, 3H), 5.98 (s, 1H), 7.00–7.10
(m, 2Harom.), 7.43–7.51 (m, 2Harom.). 19F NMR
d
: À76.75 (3F),
À112.19 (1F). 13C NMR
d
: 21.68 (CH3), 26.26 (CH3), 68.50 (q, C4,
J = 28.9 Hz), 113.63 (C5), 115.72 (d, J = 21.4 Hz), 126.72 (q, CF3,
J = 284.2 Hz), 128.92, 129.80, 129.87(Carom.), 130.79, 131.32,
163.12 (d, Carom., J = 250.2 Hz). Anal. calculated for C13H11F4NS:
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