Reactions of aromatic methyl ketimines with halonitriles as a new route to pyrimidines with two polyhaloalkyl groups

Article abstract of DOI:10.1016/S0040-4020(01)01231-5

N-Isopropyl-(1-phenylethylidene)amine reacts with trichloroacetonitrile to give 1-azabutadiene derivative, which undergoes a double addition reaction with a variety of halonitriles affording fluoro- and chloro-containing pyrimidines. Pyrimidines with two polyhaloalkyl groups were obtained by the reaction of methyl ketimines with an excess of trichloroacetonitrile, trifluoroacetonitrile and 2,2,3,3-tetrafluoropropionitrile.

Full text of DOI:10.1016/S0040-4020(01)01231-5

TETRAHEDRON
Pergamon
Tetrahedron 58 (2002) 1375±1379
Reactions of aromatic methyl ketimines with halonitriles as a new
route to pyrimidines with two polyhaloalkyl groups
a,p
Vyacheslav Ya. Sosnovskikh, Boris I. Usachev and Gerd-Volker R oÈ schenthaler
a
b
a
Department of Chemistry, Ural State University, Lenina 51, 620083 Ekaterinburg, Russia
Institute of Inorganic and Physical Chemistry, University of Bremen, 28334 Bremen, Germany
b
Received 20 September 2001; revised 15 November 2001; accepted 6 December 2001
AbstractÐN-Isopropyl-(1-phenylethylidene)amine reacts with trichloroacetonitrile to give 1-azabutadiene derivative, which undergoes a
double addition reaction with a variety of halonitriles affording ¯uoro- and chloro-containing pyrimidines. Pyrimidines with two poly-
haloalkyl groups were obtained by the reaction of methyl ketimines with an excess of trichloroacetonitrile, tri¯uoroacetonitrile and 2,2,3,3-
tetra¯uoropropionitrile. q 2002 Elsevier Science Ltd. All rights reserved.
1. Introduction
2. Results and discussion
The insertion of halogens into the a-position of aldehydes,
ketones, esters, imines and nitriles activates molecules of
these compounds with respect to nucleophilic reagents. It
has previously been shown that the condensation of methyl
ketones with ¯uoro- and chloro-containing ketones, esters
and imidoyl chlorides (iodides) in the presence of bases
As part of our continuing study on the reactivity of halo-
1
5±19
nitriles, we now report our results on the condensation
of these compounds with methyl ketimines 1a,b prepared
fromacetophenone, 2-acetothienone and isopropyla mi ne
2
0
under TiCl
CCl CN with its highly activated cyano group might react
catalysis. It seemed possible for us that
4
3
1
2,3
affords b-hydroxyketones, b-diketones and b-amino-
with ketimines 1a,b to give diimines 2 under mild
conditions. Actually, we found that N-isopropyl-(1-phenyl-
ethylidene)amine 1a existing as an equilibriummixture of
the Z- and E-isomers with the latter predominating (ca.
4
,5
vinyl ketones, respectively. The latter were also obtained
fromthe reaction of me thyl ketones with halogenated
6
,7
nitriles. Methyl ketimines react with ¯uorinated ketones
and acyl ¯uorides without a catalyst at roomtemperature to
2
1
90%) reacts with trichloroacetonitrile in a molar ratio of
1:1 without a catalyst at roomtemperature within 4 days and
leads to diimine 2, existing in the vinylogous amidine form.
This crystalline compound was obtained in high yield (74%)
and may be stored at room temperature for months without
deterioration. Hydrolysis of compound 2 to the correspond-
ing b-aminovinyl ketone 3 can be easily performed in
8
,9
10
form b-hydroxyimines and b-aminovinyl ketones, but
their reactions with ¯uorinated esters and imidoyl chlorides
proceed in the presence of diisopropylamide lithium to give
4
,11
4
b-aminovinyl ketones
exclusively isolated in the vinylogous amidine form
b-aminovinyl imines). Non-¯uorinated diimines were
obtained by reaction of Schiff bases with aromatic and
and b-diimines, which were
(
excellent yield by the action of H
roomtemperature.
SO in aqueous THF at
2 4
1
2
aliphatic nitriles in the presence of AlCl , from a-C-
3
lithiated Schiff bases and saturated nitriles, and when the
-aryl-4,6-disubstituted pyrimidin-2(1H)-ones were treated
1
3
2
2,23
1
It was shown previously
that Schiff bases derived from
1
4
with an alkoxide, both photochemically and thermally. To
the best of our knowledge, there are no reports on the
reaction of methyl ketimines with nitriles activated by
halogens.
b-diketones and aliphatic amines are present in solution to
an extent $95% as the keto-enamine by observing coupling
between the intramolecularly hydrogen-bonded proton and
the a-proton of the amine fragment. There is no apparent
1
solvent effect upon the equilibrium. In the H NMR
spectrumof 3, the methyne signal of the isopropyl group
appears as a doublet of septets at d 3.70 (JNH,CHˆ9.7 Hz,
JCH,CH3ˆ6.3 Hz). That the value of the coupling constant
JNH,CH of all the 3-aryl-3-isopropylaminoprop-2-en-1-ones
Keywords: methyl ketimines; trichloroacetonitrile; tri¯uoroacetonitrile;
24,25
is in the range 9.6±9.7 Hz
suggests that they all exist in
3
2,2,3,3-tetra¯uoro-propionitrile; CCl -containing b-aminovinyl imine and
the keto-enamine form to the same extent. In contrast,
b-aminovinyl imine 2 exists in equilibriumbetween
tautomers 2A and 2B depending on the solvent as evidenced
ketone; pyrimidines with two polyhaloalkyl groups.
Corresponding author. Fax: 17-3432-615978;
e-mail: vyacheslav.sosnovskikh@usu.ru
p
0040±4020/02/$ - see front matter q 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(01)01231-5

1376
V. Ya. Sosnovskikh et al. / Tetrahedron 58 ꢀ2002) 1375±1379
Scheme 1.
Scheme 3.
1
by its H NMR spectra (Scheme 1). In CDCl or CD CN
3
3
solution a septet with Jˆ6.3 Hz at d 3.58 ppmwas observed
When 1-azabutadiene 2 was treated with CCl CN at 808C
3
for 6 h, pyrimidine 4a with two CCl groups was obtained in
3
due to the CH proton of the isopropyl group suggesting that
2
exists in the imino-enamine form 2A. In DMSO-d6
63% yield after usual workup (Scheme 2). Although this
heterocycle could be generated by a hetero-Diels±Alder
reaction, it is more likely to suppose a double addition
reaction or an addition followed by an electrocyclic ring
solution the methyne hydrogen of 2 appears as a doublet
of septets at d 3.50 ppmdue to the additional coupling with
the NH of the enaminic form 2B. The coupling constant
between these protons was 3.1 Hz indicating an approxi-
mately 7:3 mixture of the tautomers 2A and 2B, respec-
tively, because the observed coupling is a weighted
average of the contributions from 2A and 2B. It should be
3
3
closure. Under such conditions spontaneous elimination
of isopropylamine converted the primary intermediate into
the aromatic product. The reactions of diimine 2 with
CF CN at roomtemperature and H(CF 2)2CN at 658C in a
3
0
noted that ¯uorinated N,N -disubstituted b-aminovinyl
imines exist as single tautomers with the imine fragment
sealed tube afforded pyrimidine derivatives 5a,b in good
yields. To our knowledge, this is the ®rst synthesis of
F
nearest to R group.
4
F
pyrymidines containing both the CCl and R groups in
3
the ring.
Compound 2 is an aza-analogue of the b-alkoxyvinyl-b-aryl
trichloromethyl ketones, which are readily available
building blocks for the regiospeci®c construction of
Next we examined reactions of the methyl ketimines 1a±c
with an excess of trichloroacetonitrile. On treatment with
CCl CN at 808C for 3 days, ketimine 1a gave pyrimidine
3
4a as a sole identi®able product, no diimine 2 was
detected. In contrast to the case of ketimine 1a, interaction
of N-isopropyl-[1-(2-thienyl)ethylidene]amine 1b with
trichloroacetonitrile is accompanied by resini®cation, and
we were able to isolate pyrimidine 4b only in poor yield.
At the same time, ketimine 1c prepared fromacetophenone
and 2-aminoethanol (in CDCl3 solution this compound
2
6
27
28
pyrazoles, isoxazoles, pyrimidines and benzodiaze-
2
9
pines, bearing a trichloromethyl substituent. On the other
hand, b-aminovinyl imine 2 may be considered as 1-aza-
butadiene derivative. It is well known that non-halogenated
1
-azabutadiene derivatives are useful precursors for the
synthesis of various ®ve- and six-membered heterocycles.
Thus, these compounds react with saturated nitriles and
acetylenedicarboxylic acid ester to give rise to convenient
3
0
synthetic methods for the preparation of pyrimidines and
pyridines, respectively. Fromthese results it seems likely
exists as an equilibrium mi xture of the ring and open-
chain forms ) reacts easily with CCl CN at roomtempera-
3
1
34
3
that 1-azabutadiene 2 might be a suitable precursor for
heterocycles containing the CCl group in the ring. With
ture for 2 days to give pyrimidine 4a irrespective of the
reagents ratio (Scheme 3). The maximum yield of 4a
(78%) was obtained from 1c when an excess (4.5 equiv.)
3
this in mind we have investigated the reaction of 2 with
CCl CN and R CN. The latter is potentially able to generate
F
of CCl CN was used. This reaction is the most convenient
3
3
¯
uorinated pyrimidines which are of great interest because
route to pyrimidine 4a, which owing to the labile tri-
chloromethyl substituents might be employed in the
synthesis of pyrimidines with other functional groups.
of their herbicidal, fungicidal, antibiotic, antiviral or anti-
neoplastic properties (see Ref. 32 and references therein).
Previously,
pyrimidine
methyl)pyrimidine
5-cyano-2,4-bis(trichloromethyl)-6-phenyl-
and 6-amino-5-cyano-2,4-bis(trichloro-
were obtained by two-step
3
5
3
6
a
sequence fromtrichloroacetonitrile and benzoylacetonitrile
and malononitrile, respectively.
The reactions of tri¯uoroacetonitrile and 2,2,3,3-tetra¯uoro-
propionitrile with methyl ketimines 1a,b were also investi-
gated. In this case, the ¯uorinated analogues of diimine 2
were not formed when ketimines 1a,b were treated with
F
R CN in a sealed tube. Instead, pyrimidines 6a,b and 7a,b
with two poly¯uoroalkyl groups were obtained in 78,90%
and 45,26% yields, respectively (Scheme 4). The fact that
no 1:1 adducts were observed in these reactions under
various conditions and relations of the reactants suggests a
Scheme 2.

V. Ya. Sosnovskikh et al. / Tetrahedron 58 ꢀ2002) 1375±1379
1377
In conclusion, the reaction of methyl ketimines with chloro-
and ¯uoro-containing nitriles provides a simple and con-
venient one-pot process fromthe readily available materials
to pyrimidines with two polyhaloalkyl substituents, which
are expected to be biologically active. This reaction makes it
possible to obtain pyrimidines with either the same or
different groups in the ring, which substantially enhances
its synthetic signi®cance. 1-Azabutadiene derivative 2 may
be considered as a new CCl -containing building block for
3
the synthesis of a wide variety of heterocycles with one or
two CCl groups in the ring.
3
Scheme 4.
3. Experimental
higher reactivity of the ¯uorinated nitriles in comparison to
chlorinated one. It should be noted that in the case of
H(CF ) CN the formation of 2,4,6-tris(1,1,2,2-tetra¯uoro-
3
.1. General
1
2
2
H NMR spectra were recorded on a Bruker WM-250
spectrometer operating at 250.13 MHz in CDCl solutions
ethyl)-1,3,5-triazine 8 as a product of trimerization of the
nitrile was observed. Thus, when imine 1b was heated with
an excess of H(CF ) CN in a sealed tube at 808C for 6 h a
3
with TMS as the internal standard. IR spectra were
measured on an IKS-29 instrument as suspensions in
vaseline oil. Elementary analyses were performed at the
Microanalysis Services of the Institute of Organic
Synthesis, Ural Branch, Russian Academy of Sciences.
Melting points are uncorrected. The starting methyl imines
1a±d were prepared by direct condensation of the appro-
priate carbonyl compound and amine according to described
procedure.
CF CN and H(CF ) CN were carried out in a heavy walled
2
2
mixture of pyrimidine 7b and triazine 8 was formed after
recrystallization fromethanol in exactly 3:1 mo lar ratio,
respectively. The results obtained fromvarious experiments
pointed to the following trends: higher temperatures and an
increase of the reaction time promoted triazine formation.
Previously, 2,4-bis(per¯uorooctyl)pyrimidine and 2,4,6-
tris(per¯uorooctyl)pyrimidine were prepared by using
chloro-substituted pyrimidines as substrates in copper-
mediated cross-coupling reactions with per¯uorooctyl
2
0,34,39,40
All the reactions with participation of
3
2 2
glass tube of approximately 15 ml capacity, previously
constricted for sealing.
3
7
iodide; 4,6-bis(tri¯uoromethyl)-2-methoxypyrimidine-5-
carbaldehyde was obtained from3-anilino emt hylene-
3
8
1
,1,1,5,5,5-hexa¯uoroacetylacetone and O-methylisourea.
3.1.1. 3-Isopropylimino-3-phenyl-1-trichloromethylpro-
penylamine )2ꢀ. A mixture of the ketimine 1a (5.0 g,
31.0 mmol) and trichloroacetonitrile (4.5 g, 31.2 mmol)
was kept at roomtemperature for 4 days in the dark. Then
the reaction mixture was diluted with 10 ml of 70% ethanol
and the crystalline material was isolated by ®ltration,
washed with aqueous ethanol and crystallized fromethanol
to give the title compound 2 (7.0 g, 74%) as a colourless
needles, mp 818C; (Found: C, 51.25; H, 4.90; N, 9.12.
C H Cl N requires C, 51.09; H, 4.95; N, 9.17%); n
To extend the scope of the synthesis of ¯uoro- and chloro-
containing pyrimidines, the reaction of ethylideneisopropyl-
amine 1d39 with halonitriles was studied. This reaction
showed considerably different behaviour fromthose
observed for aromatic ketimines 1a±c. For instance,
CCl CN did not react with 1d under the conditions used
3
for 1a±c and H(CF ) CN in a sealed tube both at 808C
2
2
and room temperature gave a complex mixture of at least
three products fromwhich only the crystalline previously
unknown triazine 8 was isolated in an analytically pure
1
3
15
3
2
max
2
1
3330 (NH ), 1620, 1605, 1570 (CvN, CvC) cm ; d
2
(CDCl ) 9.51 (2H, br s, NH ), 7.41 (5H, s, Ph), 5.21 (1H,
3
H
2
1
state. The H NMR spectrumof the mother liquor puri®ed
s, CHv), 3.58 (1H, sept, Jˆ6.3 Hz, CH), 1.16 (6H, d,
by distillation is best interpreted in terms of the presence of
N-isopropyl-2,2,3,3-tetra¯uoropropioamidine in an addition
to the expected 2,4-bis(1,1,2,2-tetra¯uoroethyl)pyrimidine
9 (Scheme 5). The structures of all the products (except
pyrimidine 9) were determined by their elemental analyses
Jˆ6.3 Hz, 2Me); d (CD CN) 9.46 (2H, br s, NH ), 7.34±
H
3
2
7.49 (5H, m, Ph), 5.14 (1H, s, CHv), 3.57 (1H, sept,
Jˆ6.3 Hz, CH), 1.11 (6H, d, Jˆ6.3 Hz, 2Me); d
H
(DMSO-d ) 9.43 (2H, br s, NH ), 7.44±7.50 (3H, m,
2
6
arom.), 7.34±7.36 (2H, m, arom.), 5.12 (1H, s, CHv),
3.50 (1H, d sept, JCH,NHˆ3.1 Hz, JCH,CH3ˆ6.3 Hz, CH),
and spectral data.
1
.09 (6H, d, Jˆ6.3 Hz, 2Me).
3.1.2. 1,1,1-Trichloro-4-isopropylamino-4-phenylbut-3-
en-2-one )3ꢀ. To a solution of diimine 2 (0.1 g,
.33 mmol), THF (0.5 ml) and H O (0.5 ml) was added 3
drops of conc. H SO . The mixture was stirred for 20 min at
0
2
2
4
room temperature and then was diluted with 10 ml H O. The
2
solid product obtained on standing was collected by ®ltra-
tion, washed with water and dried to give the title compound
3
(0.09 g, 90%) as a colourless needles, mp 95±968C. After
recrystallization fromethanol, the me lting point did not
change. (Found: C, 50.73; H, 4.74; N, 4.57. C H Cl NO
Scheme 5.
1
3
14
3

1378
V. Ya. Sosnovskikh et al. / Tetrahedron 58 ꢀ2002) 1375±1379
2
1580 (CvN), 1540 (CvC) cm ; d 8.47 (1H, s, H ),
8.22±8.24 (2H, m, arom.), 7.56±7.63 (3H, m, arom.).
1
5
requires C, 50.92; H, 4.60; N, 4.57%); n 1615, 1590,
575 (CvO, CvC) cm ; d 10.64 (1H, br s, NH),
.45±7.49 (3H, m, arom.), 7.35±7.40 (2H, m, arom.), 5.67
max
H
2
1
1
7
H
(
1H, s, CHv), 3.70 (1H, d sept, JCH,NHˆ9.7 Hz,
3.1.6. 4-Trichloromethyl-2-)1,1,2,2-tetra¯uoroethylꢀ-6-
phenylpyrimidine )5bꢀ. A mixture of the diimine 2
(0.3 g, 1.0 mmol) and 2,2,3,3-tetra¯uoropropionitrile
obtained from2,2,3,3-tetra¯uoropropio ai dme (1.5 g,
JCH,CH3ˆ6.3 Hz, CH), 1.22 (6H, d, Jˆ6.3 Hz, 2Me).
3.1.3. 2,4-Bis)trichloromethylꢀ-6-phenylpyrimidine )4aꢀ.
Method A. A mixture of the ketimine 1a (0.5 g, 3.1 mmol)
10.3 mmol) and P O (3.0 g) and condensed at 2408C was
2
5
and trichloroacetonitrile (1.35 g, 9.3 mmol) was heated at
8
of 70% ethanol and left overnight at roomtemperature. The
solid product obtained on standing was collected by ®ltra-
tion and crystallized fromethanol to give the title compound
kept at 658C for 16 h in a sealed tube. Then the reaction
mixture was diluted with 3 ml of 70% ethanol and the
crystalline material was recrystallized from hexane to give
the title compound 5b (0.32 g, 87%) as a colourless needles,
m p 938C; (Found: C, 41.76; H, 1.83; N, 7.42. C H Cl F N
2
08C for 3 days. The cooled mixture was diluted with 4 ml
1
3
7
3
4
4
a (0.5 g, 41%) as a colourless needles, mp 102±1038C;
Found: C, 36.95; H, 1.58; N, 7.24. C H Cl N requires
requires C, 41.80; H, 1.89; N, 7.50%); n
1545 (CvC) cm ; d 8.44 (1H, s, H ), 8.20±8.23 (2H, m,
1570 (CvN),
max
2
1
5
(
C, 36.87; H, 1.55; N, 7.17%); n
1
2
6
6
2
H
1575 (CvN), 1535
CvC) cm ; d 8.33 (1H, s, H ), 8.25±8.27 (2H, m,
arom.), 7.56±7.64 (3H, m, arom.), 6.59 (1H, tt,
max
5
2
1
2
3
(
arom.), 7.56±7.64 (3H, m, arom.).
JH,Fˆ52.9 Hz, J ˆ5.3 Hz, CF CF H).
H
H,F
2
2
3.1.7. 2,4-Bis)tri¯uoromethylꢀ-6-phenylpyrimidine )6aꢀ.
Method B. A mixture of 2-methyl-2-phenyloxazolidine 1c
(
1
A mixture of the ketimine 1a (0.5 g, 3.1 mmol) and
tri¯uoroacetonitrile obtained fromtri¯uoroacet ai dm e
(3.0 g, 26.5 mmol) and P O (6.0 g) was kept at room
0.5 g, 3.1 mmol) and trichloroacetonitrile (2.0 g,
3.9 mmol) was kept for 2 days at room temperature.
2
5
After the reaction mixture was diluted with 2 ml of 50%
acetic acid, 3 ml of ethanol and 1 drop of conc. HCl was
added for crystallization. The solid product was removed by
®ltration and crystallized fromethanol to give the title
compound 4a (0.94 g, 78%).
temperature for one day in a sealed tube. Then the reaction
mixture was diluted with 5 ml of 70% ethanol and the
crystalline material was isolated by ®ltration and washed
with ethanol to give the title compound 6a (0.71 g, 78%)
as a colourless needles, mp 101±1028C; (Found: C, 49.42;
H, 2.04; N, 9.64. C H F N requires C, 49.33; H, 2.07; N,
1
2
6
6
2
2
1
Method C. A mixture of diimine 2 (1.0 g, 3.3 mmol) and
trichloroacetonitrile (1.0 g, 6.9 mmol) was heated at 808C
for 6 h. The cooled mixture was stirred with 5 ml of 70%
ethanol and the solid product was collected by ®ltration and
crystallized fromethanol to give the title compound 4a
9.59%); nmax 1600 (CvN), 1560 (CvC) cm ; d 8.20±
H
5
8.24 (2H, m, arom.), 8.16 (1H, s, H ), 7.54±7.66 (3H, m,
arom.).
3.1.8. 2,4-Bis)1,1,2,2-tetra¯uoroethylꢀ-6-phenylpyrimi-
dine )6bꢀ. A mixture of the ketimine 1a (1.0 g, 6.2 mmol)
and 2,2,3,3-tetra¯uoropropionitrile obtained from2,2,3,3-
tetra¯uoropropioamide (6.0 g, 41.4 mmol) and P2O5
(10.0 g) was kept at 658C for 12 h in a sealed tube. Then
the reaction mixture was diluted with 10 ml of 70% ethanol
and the crystalline material was isolated by ®ltration and
crystallized fromhexane to give the title compound 6b
(2.0 g, 90%) as a colourless needles, mp 768C; (Found: C,
47.44; H, 2.27; N, 7.84. C H F N requires C, 47.21; H,
(
0.8 g, 63%).
3
)
.1.4. 2,4-Bis)trichloromethylꢀ-6-)2-thienylꢀpyrimidine
4bꢀ. A mixture of the ketimine 1b (0.5 g, 3.0 mmol) and
trichloroacetonitrile (1.3 g, 9.0 mmol) was heated at 808C
for 3 h. The cooled mixture was diluted with 10 ml of 70%
ethanol and left overnight at roomte mp erature. The dark
solid obtained on standing was collected by ®ltration,
washed with 5 ml of 70% ethanol and dissolved in 10 ml
of boiling hexane. After ®ltration and evaporation of the
solvent the residue was recrystallized twice fromethanol
to give the title compound 4b (0.1 g, 8%) as a colourless
needles, mp 105±1068C. (Found: C, 30.18; H, 1.06; N, 7.17.
C H Cl N S requires C, 30.26; H, 1.02; N, 7.06%); n
1
4
8
8
2
2
1
2.26; N, 7.86%); nmax 1600 (CvN), 1550 (CvC) cm ; d
8.20±8.23 (2H, m, arom.), 8.20 (1H, s, H ), 7.54±7.67 (3H,
H
5
2
3
m, arom.), 6.51 (1H, tt, JH,Fˆ52.9 Hz, JH,Fˆ5.1 Hz,
2
2
3
C ±CF CF H), 6.40 (1H, tt, J ˆ52.9 Hz, J ˆ5.1 Hz,
2
2
H,F
H,F
4
C ±CF CF H).
1
0
4
6
2
max
2
2
2
1
3
(
110 (vC±H), 1570 (CvN), 1520 (CvC) cm ; d 8.10
H
5
1H, s, H ), 8.01 (1H, dd, J
0
0
ˆ3.8 Hz, J
0 0
H5 ,H3
ˆ1.1 Hz,
3.1.9. 2,4-Bis)tri¯uoromethylꢀ-6-)2-thienylꢀpyrimidine
)7aꢀ. A mixture of the ketimine 1b (0.5 g, 3.0 mmol) and
tri¯uoroacetonitrile obtained fromtri¯uoroacet ai dm e
H5 ,H4
0
H ), 7.67 (1H, dd, J
0
5
3
0
0
ˆ5.0 Hz, J
0 0
ˆ1.1 Hz, H ),
H3 ,H4
H3 ,H5
0
4
7
.24 (1H, dd, J
0
0
ˆ5.0 Hz, J
0 0
ˆ3.8 Hz, H ).
H4 ,H3
H4 ,H5
(3.0 g, 26.5 mmol) and P O (5.0 g) was kept at room
2 5
3
.1.5.
4-Trichloromethyl-2-tri¯uoromethyl-6-phenyl-
temperature for one day in a sealed tube. Then the reaction
mixture was diluted with 3 ml of 70% ethanol and the
crystalline material was isolated by ®ltration and washed
with ethanol to give the title compound 7a (0.4 g, 45%)
as a colourless needles, mp 1318C; [Found: C, 40.25; H,
1.23; N, 9.46. C H F N S requires C, 40.28; H, 1.35; N,
pyrimidine )5aꢀ. A mixture of the diimine 2 (0.3 g,
.0 mmol) and tri¯uoroacetonitrile obtained from tri¯uoroa-
1
cetamide (1.5 g, 13.3 mmol) and P2O5 (3.0 g) and
condensed at 2958C was kept at roomte mp erature for
one day in a sealed tube. Then the reaction mixture was
diluted with 3 ml of 50% ethanol and the crystalline
material was recrystallized from 70% ethanol to give the
title compound 5a (0.2 g, 60%) as a colourless needles,
mp 1288C; (Found: C, 42.23; H, 1.81; N, 8.21.
C H Cl F N requires C, 42.20; H, 1.77; N, 8.20%); n
1
0
4
6
2
9.39%];
(CvC) cm ; d 7.99 (1H, dd, H , J
n
3110 (vC±H), 1600 (CvN), 1540
max
1
0
2
5
0 0
H5 ,H4
ˆ3.9 Hz,
0 0
H3 ,H4
H
5
J
4.9 Hz, J
0
0
ˆ1.2 Hz), 7.92 (1H, s, H ), 7.71 (1H, dd, J
ˆ
H5 ,H3
0
3
0
0
ˆ1.2 Hz, H ), 7.24 (1H, dd, J
0 0
H4 ,H3
ˆ4.9 Hz,
H3 ,H5
0
4
J
0 0
ˆ3.9 Hz, H ).
1
2
6
3
3
2
max
H4 ,H5

V. Ya. Sosnovskikh et al. / Tetrahedron 58 ꢀ2002) 1375±1379
1379
3
.1.10. 2,4-Bis)1,1,2,2-tetra¯uoroethylꢀ-6-)2-thienylꢀpyr-
imidine )7bꢀ. A mixture of the ketimine 1b (0.5 g,
.0 mmol) and 2,2,3,3-tetra¯uoropropionitrile obtained
8. Schlosser, M.; Keller, H. Liebigs Ann. Chem. 1995, 1587±
1589.
3
9. Przyborowski, J. PhD Thesis, University of Bremen, 1999.
10. Przyborowski, J.; Lork, E.; R oÈ schenthaler, G.-V. J. Fluorine
Chem. 2000, 104, 207±213.
from 2,2,3,3-tetra¯uoropropioamide (3.0 g, 20.7 mmol)
and 5.0 g P O was kept at roomtemperature for 2 days in
2
5
a sealed tube. Then the reaction mixture was diluted with
ml of 70% ethanol and the crystalline material was
11. Keller, H.; Schlosser, M. Tetrahedron 1996, 52, 4637±4644.
12. Hoberg, H.; Barluenga, J. Synthesis 1970, 142±144.
13. Wittig, G.; Fischer, S.; Tanaka, M. Liebigs Ann. Chem. 1973,
1075±1081.
5
isolated by ®ltration and crystallized fromhexane to give
the title compound 7b (0.28 g, 26%) as a colourless needles,
mp 102±1038C; (Found: C, 39.74; H, 1.51; N, 8.01.
C H F N S requires C, 39.79; H, 1.67; N, 7.73%); n
max
14. Nishio, T.; Omote, Y. J. Chem. Soc., Perkin Trans. 1 1982,
2149±2152.
1
2
6
8
2
2
1
3
dH 7.99 (1H, dd, J
110 (vC±H), 1600 (CvN), 1575, 1540 (CvC) cm ;
0
15. Sosnovskikh, V. Ya. Zh. Org. Khim. 1992, 28, 1307±1308.
16. Sosnovskikh, V. Ya.; Ovsyannikov, I. S. Zh. Org. Khim. 1993,
29, 89±93.
0
5
0
ˆ3.9 Hz, J
0 0
ˆ1.1 Hz, H ),
H5 ,H4
H5 ,H3
5
.97 (1H, s, H ), 7.70 (1H, dd,
7
J
J
0
0
0
ˆ5.0 Hz,
ˆ5.0 Hz,
H3 ,H4
0
3
0
0
ˆ1.1 Hz, H ), 7.24 (1H, dd, J
0
17. Sosnovskikh, V. Ya.; Ovsyannikov, I. S. Zh. Org. Khim. 1993,
29, 259±264.
H3 ,H5
H4 ,H3
2
0
4
J
0
0
ˆ3.9 Hz, H ), 6.48 (1H, tt, JH,Fˆ52.9 Hz,
H4 ,H5
3
2
2
JH,Fˆ5.2 Hz, C ±CF CF H), 6.38 (1H, tt, J ˆ52.9 Hz,
18. Sosnovskikh, V. Ya. Mendeleev Commun. 1996, 189±190.
19. Sosnovskikh, V. Ya.; Mel'nikov, M. Yu. Zh. Org. Khim. 1998,
2
2
H,F
3
4
JH,Fˆ5.2 Hz, C ±CF CF H).
2
2
3
4, 303±306.
3
.1.11. 2,4,6-Tris)1,1,2,2-tetra¯uoroethylꢀ-1,3,5-triazine
20. Weingarten, H.; Chupp, J. P.; White, W. A. J. Org. Chem.
1967, 32, 3246±3249.
)
8ꢀ. A mixture of the aldimine 1d (1.2 g, 14.0 mmol) and
,2,3,3-tetra¯uoropropionitrile obtained from2,2,3,3-tetra-
uoropropioamide (10 g, 68.9 mmol) with an excess of
P O was kept at roomtemperature for one day and then
2
¯
21. Bjùrgo, J.; Boyd, D. R.; Watson, C. G.; Jennings, W. B. J.
Chem. Soc., Perkin Trans. 2 1974, 757±762.
22. Dudek, G. O.; Holm, R. H. J. Am. Chem. Soc. 1962, 84, 2691±
2696.
2
5
at 808C for 2 h in a sealed tube. Then the reaction mixture
was distillated under reduce pressure and the crystalline
material was isolated by ®ltration and crystallized from
ethanol to give the title compound 8 (0.7 g) as a white
crystals, mp 938C; (Found: C, 28.39; H, 0.68; N, 11.08.
C H F N requires C, 28.36; H, 0.79; N, 11.03%); n
max
23. Brown, N. M. D.; Nonhebel, D. C. Tetrahedron 1968, 24,
5655±5664.
24. Cimarelli, C.; Palmieri, G. Tetrahedron 2000, 56, 475±478.
25. Sosnovskikh, V. Ya.; Usachev, B. I. Unpublished data.
26. Martins, M. A. P.; Freitag, R. A.; da Rosa, A.; Flores, A. F. C.;
Zanatta, N.; Bonacorso, H. G. J. Heterocycl. Chem. 1999, 36,
217±220.
9
3
12
3
2
1
2
1
560 (CvN) cm ; d 6.40 (3H, tt, JH,Fˆ52.5 Hz,
H
3
JH,Fˆ4.3 Hz, 3CF CF H).
2
2
2
7. Martins, M. A. P.; Flores, A. F. C.; Bastos, G. P.; Sinhorin, A.;
Bonacorso, H. G.; Zanatta, N. Tetrahedron Lett. 2000, 41,
293±297.
2,4-Bis(1,1,2,2-tetra¯uoroethyl)pyrimidine 9 (a colourless
oil) was not isolated in a pure state; nmax(liquid ®lm)
3
1
550, 3510, 3450, 3360, 3220, 3120, 1690, 1635, 1605,
28. Madruga, C. C.; Clerici, E.; Martins, M. A. P.; Zanatta, N.
J. Heterocycl. Chem. 1995, 32, 735±738.
2
1
2
3
570 cm ; d 6.35 (1H, tt, J ˆ52.8 Hz, J ˆ4.8 Hz,
H
H,F
H,F
4
2
3
C ±CF CF H), 6.44 (1H, tt, J ˆ52.9 Hz, J ˆ4.9 Hz,
29. Bonacorso, H. G.; Bittencourt, S. R. T.; Wastowski, A. D.;
Wentz, A. P.; Zanatta, N.; Martins, M. A. P. J. Heterocycl.
Chem. 1999, 36, 45±48.
2
2
H,F
H,F
2
5
C ±CF CF H), 7.88 (1H, d, Jˆ5.1 Hz, H ), 9.17 (1H, d,
2
2
6
Jˆ5.1 Hz, H ).
30. Hoberg, H.; Barluenga, J. Synthesis 1970, 363±365.
31. Barluenga, J.; Fustero, S.; Gotor, V. Synthesis 1975, 191±192.
Acknowledgements
Financial support by the Deutsche Forschungsgemeinschaft
32. Sevenard, D. V.; Khomutov, O. G.; Koryakova, O. V.;
Sattarova, V. V.; Kodess, M. I.; Stelten, J.; Loop, I.; Lork,
E.; Pashkevich, K. I.; R oÈ schenthaler, G.-V. Synthesis 2000,
1738±1748.
(
436 RUS 17/105/00) is gratefully acknowledged.
3
3. Barluenga, J.; Rubio, V.; Gotor, V. J. Org. Chem. 1980, 45,
592±2596.
2
References
34. F uÈ l oÈ p, F.; Pihlaja, K.; Neuvonen, K.; Berna
K a lm a n, A. J. Org. Chem. 1993, 53, 1967±1969.
35. Elnagdi, M. H.; Fahmy, S. M.; Hafez, E. A. A.; Elmoghayar,
M. R. H.; Amer, S. A. R. J. Heterocycl. Chem. 1979, 16,
1109±1111.
Âth, G.; Argay, G.;
1
2
3
4
. Sosnovskikh, V. Ya.; Ovsyannikov, I. S.; Aleksandrova, I. A.
Zh. Org. Khim. 1992, 28, 518±526.
. Reid, J. C.; Calvin, M. J. Am. Chem. Soc. 1950, 72, 2948±
2
952.
. Barkley, L. B.; Levine, R. J. Am. Chem. Soc. 1951, 73, 4625±
627.
36. Elnagdi, M. H.; Elfahham, H. A.; Ghozlan, S. A. S.; Elgemeie,
G. E. H. J. Chem. Soc., Perkin Trans. 1 1982, 2667±2670.
37. Chen, G. J.; Chen, L. S. J. Fluorine Chem. 1995, 73, 113±119.
38. Soufyane, M.; van den Broek, S.; Khamliche, L.; Mirand, C.
Heterocycles 1999, 51, 2445±2451.
4
. Fustero, S.; de la Torre, M. G.; Pina, B.; Fuentes, A. S. J. Org.
Chem. 1999, 64, 5551±5556.
5
. Yu, H.-B.; Huang, W.-Y. J. Fluorine Chem. 1997, 84, 65±67.
. Sosnovskikh, V. Ya.; Ovsyannikov, I. S. Zh. Org. Khim. 1990,
39. Snyder, H. R.; Matteson, D. S. J. Am. Chem. Soc. 1957, 79,
2217±2221.
6
2
6, 2086±2091.
. Pashkevich, K. I.; Aizikovich, A. Ya. Dokl. AN SSSR 1979,
44, 618±620.
40. Campbell, K. N.; Sommers, A. H.; Campbell, B. K. J. Am.
Chem. Soc. 1944, 66, 82±84.
7
2