Synthesis of 1,3,6-Triaryl-6-trifluoromethyl-5,6-dihydro-1,3,5-triazine-2, 4(1H,3H)-diones by reaction of aryl trifluoromethyl ketone imines with aryl isocyanates

Full text of DOI:10.1134/S1070428012040318

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2012, Vol. 48, No. 4, pp. 618–619. © Pleiades Publishing, Ltd., 2012.
Original Russian Text © N.V. Mel’nichenko, M.V. Vovk, 2012, published in Zhurnal Organicheskoi Khimii, 2012, Vol. 48, No. 4, pp. 618–619.
SHORT
COMMUNICATIONS
Synthesis of 1,3,6-Triaryl-6-trifluoromethyl-
5,6-dihydro-1,3,5-triazine-2,4(1H,3H)-diones by Reaction
of Aryl Trifluoromethyl Ketone Imines with Aryl Isocyanates
N. V. Mel’nichenko and M. V. Vovk
Institute of Organic Chemistry, National Academy of Sciences of Ukraine,
ul. Murmanskaya 5, Kiev, 02094 Ukraine
e-mail: mvovk@i.com.ua
Received July 23, 2011
DOI: 10.1134/S1070428012040318
IIc only in the presence of a catalytic amount of
a strong organic base (1,4-diazabicyclo[2.2.2]octane,
DABCO) to produce 1,3,6-triaryl-6-trifluoromethyl-
5,6-dihydro-1,3,5-triazine-2,4(1H,3H)-diones ІІІa–
IIIe. The use of 2 equiv of aryl isocyanate II and
prolonged heating (18–20 h) allowed us to attain a 52–
70% yield of compounds ІІІ. Most probably, the initial
step is base-catalyzed addition of aryl isocyanate II at
the nitrogen atom of imine I with formation of
N-(1-aryl-2,2,2-trifluoroethylidene)urea A which is
capable of undergoing tautomeric transformation into
3-hydroxy-2,4-diaza-1,3-diene B at elevated tempera-
ture. Provided that excess aryl isocyanate is present in
the reaction mixture, intermediate B does not undergo
intramolecular cyclization with formation of quinaz-
olin-2-one [5] but gives rise to triazinedione III via
[4+2]-cycloaddition with the second aryl isocyanate
molecule. The proposed scheme was indirectly sup-
ported by the GC–MS data, according to which the
reaction mixtures contained up to 7–10% of N-al-
kylideneurea like A.
Because of reduced basicity, carbamoylation of aryl
trifluoromethyl ketone imines at the nitrogen atom
occurs under mild conditions only by the action of
highly electrophilic reagents, such as trichloromethyl
isocyanate [1], 1-aryl-1-chloro-2,2,2-trifluoroethyl iso-
cyanates [2], and chlorocarbonyl isocyanate [3]. The
reactions with 1-chloroalkyl isocyanates give the cor-
responding N,N′-bis(alkylidene)ureas which are inter-
mediate products in the synthesis of trifluoromethyl-
containing N,N′-bis(1-chloroalkyl)carbodiimides [4].
Our attempts to effect carbamoylation of aryl trifluoro-
methyl ketone imines with aryl isocyanates in the tem-
perature range from 20 to 110°C were unsuccessful.
Therefore, N-aryl-N′-(2,2,2-trifluoroethylidene)ureas
as important initial compounds for the synthesis of
4-trifluoromethylquinazolin-2-ones [5] and their benzo
analogs [6] were obtained by reaction of 1-aryl-1-
chloro-2,2,2-trifluoroethyl isocyanates with aromatic
amines. Taking into account recently reported data [7]
on N-acylation of aryl trifluoromethyl ketone imines
with alkyl chloroformates at elevated temperature, we
examined the reaction of ketone imines Іa–Ic with aryl
isocyanates IІa–IIc in boiling xylene with a view to
synthesize N-aryl-N′-(2,2,2-trifluoroethylidene)ureas.
However, imines Іa–Ic reacted with isocyanates ІІa–
1,3,6-Triaryl-6-trifluoromethyl-5,6-dihydro-
1,3,5-triazine-2,4(1H,3H)-diones ІІІa–IIIe (general
procedure). A mixture of 1 mmol of ketone imne Іa–
Ic, 2 mmol of aryl isocyanate ІІa–IIc, a catalytic
Ar2
O
N
O
Ar1
O
Ar1
OH
NH
IIa–IIc
DABCO
N
Ar2
·
+
HN
Ar1
N
Ar1
CF3
F3C
N
NHAr2
F3C
N
NAr2
O
Ar2
CF3
Ia–Ic
IIa–IIc
A
B
IIIa–IIIe
І, Ar1 = Ph (a), 3-FC6H4 (b), 3-MeC6H4 (c); ІІ, Ar2 = 4-ClC6H4 (a), 4-t-BuC6H4 (b), 3,4-Cl2C6H3 (c); III, Ar1 = Ph, Ar2 = 4-Cl6H4 (a),
3,4-Cl2C6H3 (b); Ar1 = 3-FC6H4, Ar2 = 4-t-BuC6H4 (c), 3,4-Cl2C6H3 (d); Ar1 = 3-MeC6H4, Ar2 = 4-ClC6H4 (e).
618

SYNTHESIS OF 1,3,6-TRIARYL-6-TRIFLUOROMETHYL-5,6-DIHYDRO-1,3,5-TRIAZINE-...
619
amount of DABCO, and 15 ml of xylene (isomer mix-
ture) was heated for 18–20 h under reflux. The mixture
was cooled, and the precipitate was filtered off,
washed with hexane, and purified by recrystallization.
ppm: 7.18–7.69 m (10H, Harom), 10.17 s (1H, NH).
13C NMR spectrum, δC, ppm: 74.64 q (C6, JCF
=
31.4 Hz), 124.18 q (CF3, JCF = 298.8 Hz), 114.43,
116.96, 117.71, 124.78, 129.73, 129.79, 130.25,
130.39, 130.84, 131.15, 131.50, 133.19, 134.36,
134.83, 136.45, 140.80, 141.38 (Carom), 150.03 (C=O),
150.15 (C=O), 161.74 d (C3′F, J = 254.4 Hz). 19F NMR
spectrum: δF –74.12 ppm (CF3). Found, %: C 46.68;
H 2.22; N 7.66. m/z 567 [M + 1]+. C30H31F4N3O2. Cal-
culated, %: C 46.59; H 1.95; N 7.41. M 567.2.
1,5-Bis(4-chlorophenyl)-6-(3-methylphenyl)-
6-trifluoromethyl-5,6-dihydro-1,3,5-triazine-
2,4(1H,3H)-dione (ІІІe). Yield 54%, mp 162–163°C
(from benzene–hexane, 1:1). IR spectrum, ν, cm–1:
3240 (N–H), 1730, 1680 (C=O). 1H NMR spectrum, δ,
ppm: 2.32 s (3H, CH3), 7.23–7.59 m (12H, Harom),
9.91 s (1H, NH). 13C NMR spectrum, δC, ppm: 20.97
(CH3), 75.04 q (C6, JCF = 31.6 Hz), 125.22 q (CF3,
JCF = 288.2 Hz), 128.15, 128.20, 128.26, 128.69,
129.23, 130.80, 131.22, 132.13, 132.63, 132.69,
132.84, 134.01, 135.66, 137.77 (Carom), 150.47 (C=O),
150.53 (C=O). 19F NMR spectrum: δF –73.78 ppm
(CF3). Found, %: C 48.77; H 2.64; N 7.31. m/z 564
[M + 1]+. C23H14Cl4F3N3O2. Calculated, %: C 49.05;
H 2.51; N 7.46. M 563.2
1,3-Bis(4-chlorophenyl)-6-phenyl-6-trifluoro-
methyl-5,6-dihydro-1,3,5-triazine-2,4(1H,3H)-dione
(ІІІa). Yield 59%, mp 225–227°C (from benzene–
hexane, 2:1). IR spectrum, ν, cm–1: 3265 (N–H), 1740,
1
1690 (C=O). H NMR spectrum, δ, ppm: 7.24–7.86 m
(13H, Harom), 9.98 s (1H, NH). 13C NMR spectrum, δC,
ppm: 75.10 q (C6, JCF = 30.2 Hz), 124.76 q (CF3, JCF
=
287.6 Hz), 128.24, 128.38, 128.40, 128.67, 130.25,
131.20, 132.19, 132.63, 132.68, 132.83, 133.98,
135.62 (Carom), 150.45 (C=O), 150.49 (C=O). 19F NMR
spectrum: δF –73.81 ppm (CF3). Found, %: C 54.75;
H 3.07; N 8.56. m/z 481 [M + 1]+. C22H14Cl2F3N3O2.
Calculated, %: C 55.02; H 2.94; N 8.75. M 480.3.
1,5-Bis(3,4-dichlorophenyl)-6-phenyl-6-trifluoro-
methyl)-5,6-dihydro-1,3,5-triazine-2,4(1H,3H)-di-
one (ІІІb). Yield 52%, mp 238–240°C (from benzene–
hexane, 1:1). IR spectrum, ν, cm–1: 3260 (N–H), 1745,
1
1695 (C=O). H NMR spectrum, δ, ppm: 7.17–7.77 m
(11H, Harom), 10.09 s (1H, NH). 13C NMR spectrum,
δC, ppm: 75.31 q (C6, JCF = 29.8 Hz), 124.60 q (CF3,
JCF = 284.8 Hz), 127.43, 128.46, 129.91, 130.05,
130.40, 130.49, 130.56, 130.82, 131.02, 131.10,
131.25, 131.55, 1341.89, 133.20, 134.89, 136.55
(Carom), 150.18 (C=O), 150.20 (C=O). 19F NMR spec-
trum: δF –73.76 ppm (CF3). Found, %: C 48.39;
H 2.04; N 7.50. m/z 550 [M + 1]+. C22H12Cl4F3N3O2.
Calculated, %: C 48.12; H 2.20; N 7.65. M 549.2.
The IR spectra were recorded in KBr on a UR-20
1
instrument. The H and 13C NMR spectra were
recorded from solutions in DMSO-d6 on a Bruker
Avance DRX-500 spectrometer at 500.13 and
125.75 MHz, respectively, using TMS as internal refer-
ence. The 19F NMR spectra were measured from solu-
tions in DMSO-d6 on a Varian Gemini instrument at
188.14 MHz using CFCl3 as internal reference. The
mass spectra were obtained on an Agilent
1100\DAD\HSD\VLG 119562 GC–MS system. Initial
imines Ia–Ic were synthesized as described in [1].
1,5-Bis(4-tert-butylphenyl)-6-(3-fluorophenyl)-
6-trifluoromethyl-5,6-dihydro-1,3,5-triazine-
2,4(1H,3H)-dione (ІІІc). Yield 58%, mp 245–247°C
(from aqueous ethanol, 1:1). IR spectrum, ν, cm–1:
3230 (N–H), 1735, 1680 (C=O). 1H NMR spectrum, δ,
ppm: 1.17 s and 1.27 s (9H each, t-Bu), 6.84–7.56 m
(12H, Harom), 9.89 s (1H, NH). 13C NMR spectrum, δC,
ppm: 30.85 and 31.09 (CH3), 34.15 and 34.34
[C(CH3)3], 74.71 q (C6, JCF = 32.2 Hz), 124.25 q (CF3,
JCF = 292.4 Hz), 115.93, 117.96, 124.91, 125.28,
125.37, 126.00, 128.73, 130.20, 130.47, 132.55,
133.96, 135.03, 143.95 (Carom), 150.32 (C=O), 150.74
(C=O), 161.52 d (C3′F, J = 251.6 Hz). 19F NMR spec-
trum: δF –74.04 ppm (CF3). Found, %: C 66.30;
H 5.77; N 7.86. m/z 542 [M + 1]+. C30H31F4N3O2. Cal-
culated, %: C 66.53; H 5.77; N 7.76. M 541.6.
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1,5-Bis(3,4-dichlorophenyl)-6-(3-fluorophenyl)-
6-trifluoromethyl-5,6-dihydro-1,3,5-triazine-
2,4(1H,3H)-dione (ІІІd). Yield 63%, mp 239–241°C
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3250 (N–H), 1730, 1685 (C=O). 1H NMR spectrum, δ,
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