Synthesis of 2-aryl-2,4,6-tris(trifluoromethyl)-1,2-dihydro-1,3,5-triazines by reaction of arylmagnesium bromides with trifluoroacetonitrile

Full text of DOI:10.1134/S1070428007060231

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2007, Vol. 43, No. 6, pp. 928–929. © Pleiades Publishing, Ltd., 2007.
Original Russian Text © M.V. Vovk, A.V. Bol’but, P.S. Lebed’, N.V. Mel’nichenko, 2007, published in Zhurnal Organicheskoi Khimii, 2007, Vol. 43, No. 6,
pp. 929–930.
SHORT
COMMUNICATIONS
Synthesis of 2-Aryl-2,4,6-tris(trifluoromethyl)-1,2-dihydro-
1,3,5-triazines by Reaction of Arylmagnesium Bromides
with Trifluoroacetonitrile
M. V. Vovk, A. V. Bol’but, P. S. Lebed’, and N. V. Mel’nichenko
Institute of Organic Chemistry, National Academy of Sciences of Ukraine,
ul. Murmanskaya 5, Kiev, 02660 Ukraine
e-mail: mvovk@i.com.ua
Received November 15, 2006
DOI: 10.1134/S1070428007060231
(ІІb) as an example we have shown that the yields of
compounds ІІb and IIIb decrease by 6 and 4%, re-
spectively, when an equimolar amount of trifluoroacet-
amide is used. Presumably, the reason is the reduced
conversion of trifluoroacetamide into trifluoroaceto-
nitrile. On the other hand, in the presence of 3 equiv of
trifluoroacetamide the yield of triazine ІІІb increases
to 66%. These results led us to presume the following
reaction scheme. Initially formed ketone imine salt A
adds to trifluoroacetonitrile to give diaza diene inter-
mediate B which undergoes intermolecular cyclization
with another trifluoroacetonitrile molecule. Methanol-
ysis of triazine derivative C thus formed yields com-
pounds ІІІa–IIId.
Reaction of arylmagnesium bromides with tri-
fluoroacetonitrile underlies a preparative procedure for
the synthesis of aryl trifluoromethyl ketone imines
[1, 2]. According to [1], the yields of the target prod-
ucts attain 50–60% at an arylmagnesium bromide–tri-
fluoroacetamide (precursor of trifluoroacetonitrile)
ratio of 1:1.2. The structure of minor products in this
reaction remains unexplored; however, we believe it to
be important from the viewpoint of development of
optimal conditions for the synthesis of the correspond-
ing ketone imines. While attempting to reproduce the
procedure described in [1] we have found that, apart
from aryl trifluoromethyl ketone imines ІІa–IId, 18–
26% of 2-aryl-2,4,6-tris(trifluoromethyl)-1,2-dihydro-
1,3,5-triazines ІІІa–IIId is formed in reactions of aryl-
magnesium bromides Іa–Id with trifluoroacetonitrile.
Using the reaction with p-tolylmagnesium bromide
1-Aryl-2,2,2-trifluoroethanimines ІІa–IId and
2-aryl-2,4,6-tris(trifluoromethyl)-1,2-dihydro-1,3,5-
triazines ІІІa–IIId (general procedure). A stream of
F3C
F3C
NH
MeOH
ArMgBr
+
CF3CN
NMgBr
Ar
Ar
Ia–Id
A
IIa–IId
CF3CN
MgBr
H
Ar
F3C
Ar
F3C
F3C
Ar
N
CF3
N
CF3
CF3CN
MeOH
N
N
N
N
N
NMgBr
F3C
CF3
CF3
IIIa–IIId
B
C
Ar = Ph (a), 4-MeC6H4 (b), 4-MeOC6H4 (c), 2-Me-5-FC6H3 (d).
928

SYNTHESIS OF 2-ARYL-2,4,6-TRIS(TRIFLUOROMETHYL)-1,2-DIHYDRO-1,3,5-TRIAZINES
929
trifluoroacetonitrile [prepared by heating a mixture of
81.36 g (0.72 mol) of trifluoroacetamide and 213 g
(1.5 mol) of phosphoric anhydride to 140–150°C] was
passed over a period of 4–5 h under stirring through
a solution of arylmagnesium bromide Іa–Id, prepared
from 0.6 mol of the corresponding aryl bromide and
14.4 g (0.6 mol) of metallic magnesium in 600 ml of
diethyl ether. The mixture was left to stand for 12 h,
and 60 ml of methanol was added over a period of
0.5 h under vigorous stirring. After cooling, the precip-
itate was filtered off, the filtrate was evaporated, and
the residue was subjected to fractional distillation.
Yields of compounds IIa, ІІb, and ІІc 53, 50, and
48%, respectively.
19F NMR spectrum, δF, ppm: –82.68 s (CF3), –74.21 s
(2CF3). Found, %: F 45.55; N 11.03. C13H8F9N3. Cal-
culated, %: F 45.33; N 11.14.
2-(4-Methoxyphenyl)-2,4,6-tris(trifluoromethyl)-
1,2-dihydro-1,3,5-triazine (ІІІc). Yield 26%, bp 80–
81°C (0.045 mm), mp 94–95°C. 1H NMR spectrum, δ,
ppm: 3.82 s (3H, OCH3), 6.93 d (2H, Harom), 7.58 d
13
(2H, Harom), 7.99 br.s (1H, NH). C NMR spectrum,
2
δC, ppm: 55.33 (OCH3), 77.12 q (C2, JCF = 31 Hz),
1
114.02 (C3′, C5′), 116.52 q (CF3, JCF = 277 Hz),
122.42 q (CF3, 1JCF = 284 Hz), 126.78 (C2′, C6′), 128.10
2
(C1′), 142.18 q (C4, C6, JCF = 39 Hz), 160.64 (C4′).
19F NMR spectrum, δF, ppm: –81.31 s (CF3), –73.20 s
(2CF3). Found, %: F 43.65; N 10.47. C13H8F9N3O.
Calculated, %: F 43.48; N 10.69.
2,2,2-Trifluoro-1-(5-fluoro-2-methylphenyl)-
ethanimine (ІІd) (a mixture of Z and E isomers).
Yield 49%, bp 93–95°C (12 mm). H NMR spectrum,
2-(5-Fluoro-2-methylphenyl)-2,4,6-tris(trifluoro-
1
methyl)-1,2-dihydro-1,3,5-triazine (ІІІd). Yield 23%,
1
δ, ppm: 1.67 s, 2.05 s (3H, CH3), 6.48–6.72 m (4H,
bp 133–135°C (12 mm), mp 94–95°C. H NMR spec-
H
arom), 9.76 s and 10.84 s (1H, NH). 19F NMR spec-
trum (CDCl3), δ, ppm: 2.54 s (3H, CH3), 6.92–6.98 m
(1H, Harom), 7.26 t (1H, Harom), 7.34 d (1H, Harom),
8.03 br.s (1H, NH). 13C NMR spectrum, δC, ppm:
21.19 (CH3), 79.50 q (C2, 2JCF = 32 Hz), 115.33 d (C4′,
trum, δF, ppm: –71.51 s and –72.85 s (3F, CF3),
–116.1 s and –116.5 s (1F). Found, %: F 37.21; N 6.99.
C9H10F4N. Calculated, %: F 37.04; N 6.83.
1
2JCF = 26 Hz), 118.49 q (4-CF3, JCF = 212 Hz),
2-Phenyl-2,4,6-tris(trifluoromethyl)-1,2-dihydro-
1,3,5-triazine (ІІІa). Yield 18%, bp 52°C (0.045 mm).
1H NMR spectrum, δ, ppm: 7.43 m (3H, Harom), 7.67 m
(2H, Harom), 8.31 br.s (1H, NH). 13C NMR spectrum,
2
1
116.61 d (C6′, JCF = 21 Hz), 122.73 q (6-CF3, JCF
=
284 Hz ), 133.83 d (C2′, JCF = 2.5 Hz), 134.60 d (C3′,
4
3JCF = 7.5 Hz), 135.89 d (C1′, JCF = 3.7 Hz), 142.10 q
3
(C4, C6, JCF = 39 Hz), 160.51 d (C5′, JCF = 244 Hz).
19F NMR spectrum, δF, ppm: –74.04 s (2CF3), –81.29 s
(CF3), –117.43 s (F). Found, %: F 47.98; N 10.57.
C13H7F10N3. Calculated, %: F 48.07; N 10.63.
2
1
2
δC, ppm: 78.76 q (C2, JCF = 30 Hz), 116.49 q (CF3,
1JCF = 277 Hz), 122.35 q (CF3, 1JCF = 284 Hz), 125.41
(C4′), 127.74 (C2′, C6′), 128.68 (C3′, C5′), 136.91 (C1′),
2
19
142.31 q (C4, C6, JCF = 42 Hz). F NMR spectrum,
δF, ppm: –82.32 s (CF3), –74.41 s (2CF3). Found, %:
F 47.24; N 11.79. C12H6F9N3. Calculated, %: F 47.08;
N 11.57.
The H, 13C, and 19F NMR spectra were recorded
1
from solutions in CDCl3 on a Varian-Gemini spec-
trometer at 299.95, 75.4, and 282.2 MHz, respectively;
the chemical shifts were measured relative to tetra-
methylsilane (1H, 13C) and trichlorofluoromethane
(19F) as internal references.
2-(4-Methylphenyl)-2,4,6-tris(trifluoromethyl)-
1,2-dihydro-1,3,5-triazine (ІІІb). Yield 21%, bp 120–
1
123°C (12 mm), mp 42–43°C. H NMR spectrum, δ,
ppm: 2.38 s (3H, CH3), 7.24 d (2H, Harom), 7.55 d (2H,
REFERENCES
H
arom), 8.35 br.s (1H, NH). 13C NMR spectrum, δC,
ppm: 2.13 (CH3), 78.50 q (C2, 2JCF = 30 Hz), 116.51 q
1. Fetyukhin, V.N., Koretskii, A.S., Gorbatenko, V.I., and
Samarai, L.I., Zh. Org. Khim., 1977, vol. 13, p. 271.
2. Koos, M. and Mosher, H.S., Tetrahedron, 1993, vol. 49,
1
1
(4-CF3, JCF = 275 Hz), 122.42 q (6-CF3, JCF
=
284 Hz), 126.52 (C2′, C6′), 129.27 (C3′, C5′), 133.85
(C1′), 140.11 (C4′), 142.09 q (C4, C6, JCF = 40 Hz).
2
p. 1541.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 43 No. 6 2007