4-Nitrophenyln-(1-aryl-2,2,2-trifluoroethylidene)urethanes: Novel 1,3-electrophilic components of reactions leading to 6- and 7-membered heterocycles

Article abstract of DOI:10.1023/B:COHC.0000027899.14391.07

We propose an approach to synthesis of N,O,S-containing 6- and 7-membered heterocycles based on using 4-nitrophenyl N-(1-aryl-2,2,2-trifluoroethylidene) urethanes as the electrophilic components in heterocyclizations with bifunctional nucleophilic reagent

Full text of DOI:10.1023/B:COHC.0000027899.14391.07

Chemistry of Heterocyclic Compounds, Vol. 40, No. 2, 2004
4-NITROPHENYL N-(1-ARYL-2,2,2-TRIFLUORO-
ETHYLIDENE)URETHANES: NOVEL
1,3-ELECTROPHILIC COMPONENTS OF
REACTIONS LEADING TO 6- AND
7-MEMBERED HETEROCYCLES
M. V. Vovk, V. I. Dorokhov, and L. I. Samarai
We propose an approach to synthesis of N,O,S-containing 6- and 7-membered heterocycles based on
using 4-nitrophenyl N-(1-aryl-2,2,2-trifluoroethylidene)urethanes as the electrophilic components in
heterocyclizations with bifunctional nucleophilic reagents.
Keywords: N-alkylideneurethanes, bifunctional nucleophiles, 5-oxoimidazo[2,3-b]-1,3,5-thiadiazines,
2-oxo-1,5,3-oxathiazepines, 2-oxo-1,5,3-benzoxathiazepines.
N-Alkylideneurethanes have been used as 1,2- or 1,4-components in cycloaddition reactions with
electron-rich reagents [1].
O
H
N
N
O
YH
HX
OR
YH
+
–ROH
OR
X
1
2–4
5
H
N
N
C
O
O
X
Y
X
YH
7–9
6
We have significantly expanded the synthetic possibilities of N-alkylideneurethanes by using them as
1,3-electrophilic components in heterocyclizations with bifunctional nucleophilic substrates. The proposed
approach essentially involves addition of bifunctional nucleophiles 2-4 to N-alkylideneurethanes 1, which leads
to formation of acyclic products 5, followed by generation under the reaction conditions of isocyanates of type 6
and their intramolecular cyclization to hetero systems 7-9.
__________________________________________________________________________________________
Institute of Organic Chemistry, National Academy of Sciences of Ukraine, Kiev 02094; e-mail:
hetfos@ukrpack.net; mvovk@i.com.ua. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2,
pp. 282-285, February, 2004. Original article submitted June 26, 2001.
0009-3122/04/4002-0241©2004 Plenum Publishing Corporation
241

O
Ar
N
O
NO2
CF3
1a,b
–
O2N
SH
OH
H
N
SH
S
OH
OH
N
H
2
4
3
CF3
Ar
NH
CF3
Ar
CF3
Ar
S
S
S
N
NH
N
NH
O
9a,b
O
O
O
O
7a,b
8a,b
1, 7–9 a Ar = Ph, b Ar = 4-MeC6H4
The pronounced electrophilicity of the azomethine group in urethanes 1 helps the reaction occur
regioselectively as a result of the formation of urethanes 5, which cannot always be successfully achieved in
cyclizations with participation of 1-chloroalkyl isocyanates [2]. A necessary condition for the heterocyclization
is the ability of urethanes 5 to generate synthons 6, which first of all depends on the nature of the substituent R.
We have established that such a requirement is satisfied by 4-nitrophenyl N-alkylideneurethanes 1, since under
mild conditions (benzene, 80°C) the corresponding urethanes 5 tend to readily eliminate 4-nitrophenol with
formation of isocyanates 6, which is detected by IR spectroscopy. Such properties are lacking in 4-nitrophenyl
N-alkylideneurethanes 1 (R = CH3, CH2C6H5), and for this reason they cannot be used as components for
cyclizations, since the corresponding urethanes 5 do not undergo further conversions either at 80°C or at higher
temperatures (110-140°C).
The approach considered above for synthesis of hetero systems 7-9 is illustrated by the examples of
cyclocondensations of 4-nitrophenyl N-(1-aryl-2,2,2-trifluoroethylidene)urethanes 1a,b with bifunctional
nucleophiles: 2-imidazoline thione 2, 2-mercaptoethanol 3, and 2-mercaptophenol 4. We have shown that when
the reagents are heated in benzene, we obtain the target products in high yields: derivatives of 3-aryl-5-oxo-3-
trifluoromethyl-6,7-dihydroimidazo[2,3-b]-1,3,5-thiadiazines 7a,b [3], 4-aryl-2-oxo-4-trifluoromethyl-1,5,3-
oxathiazepines 8a,b, and 4-aryl-2-oxo-4-trifluoromethyl-1,5,3-benzoxathiazepines 9a,b.
Compounds 7a,b-9a,b (Table 1) are colorless crystalline compounds, the individual purity of which was
shown by TLC while their composition was determined by elemental analysis results and their structure was
1
proven by IR, H and 19F NMR spectra (Table 2). The IR spectra of compounds 7a,b are characterized by
absorption bands for the carbonyl groups of the ureide moiety in the 1660-1680 cm-1 region, while compounds
8a,b, 9a,b are characterized by absorption bands for the carbonyl groups of the urethane moiety in the
1
1740-1770 cm-1 region. In the H NMR spectra of all the compounds, along with signals from methyl,
methylene, and aromatic protons, we see broadened singlets for the N–H protons at 7.80-8.50 ppm. The presence
of the same signals in the 19F NMR spectra for both the reaction mixtures and the end products is evidence for
the regioselectivity of the cyclization process. The region where we see the 74-77 ppm signals indicates that the
CF3 groups are located on the sp3-hybridized carbon atom of the S–C–N moiety, and supports a cyclic structure
for the compounds obtained [4].
242

TABLE 1. Characteristics of Synthesized Compounds
Found, %
Com-
pound
Empirical
formula
mp, °C (solvent for
crystallization)
——————
Calculated, %
Yield, %
C
H
S
7а
7b
8а
8b
9а
9b
С12Н10F3N3OS
С13Н12F3N3OS
С11Н10F3NO2S
С12Н12F3NO2S
С15Н10F3NO2S
С16Н12F3NO2S
47.98
47.84
3.11
3.35
10.74
10.64
146-147
(hexane–benzene, 2:1)
69
78
64
70
57
68
50.01
49.52
3.91
3.84
10.50
10.17
179-180
(hexane–benzene, 1:8)
47.39
47.65
3.78
3.63
11.27
11.56
56-57
(hexane–diethyl ether, 2:1)
49.30
49.47
4.45
4.15
11.12
11.01
69-70
(hexane–diethyl ether, 2:1)
55.69
55.38
3.34
3.10
9.57
9.85
88-89
(hexane–benzene, 8:1)
77-78
(hexane–benzene, 5:1)
56.68
56.63
3.30
3.56
9.56
9.45
TABLE 2. Spectral Characteristics of Compounds 7-9
IR spectrum, ν, cm-1
Com-
19F NMR
spectra,
δ, ppm
1H NMR spectra, δ, ppm
pound
С=О
N–H
7а
7b
8а
1665
1660
1750
3240
3220
3.80-3.98 (4Н, m, СН2); 7.37-7.41 (5Н, m, Harom.);
9.84 (1Н, br. s, NH)
76.2
76.2
74.5
2.29 (3Н, s, СН3); 3.78-3.95 (4Н, m, CН2);
7.15-7.54 (4Н, m, С6Н4); 9.67 (1Н, br. s, NH)
3250
3400
2.72-2.87 (2Н, m, СН2S); 4.22-4.38 (2Н, m, CH2O);
7.42-7.61 (5Н, m, С6H5); 8.15 (1Н, br. s, NH)
8b
1745
3250
3400
2.38 (3Н, s, СН3); 2.95-3.17 (2Н, m, CН2S);
4.15-4.35 (2Н, m, СН2O); 7.18-7.47 (4H, m, С6Н4);
8.00 (1Н, br. s, NH)
75.7
9а
1750
1765
3290
3380
7.12-7.50 (9Н, m, Нarom); 7.80 (1Н, br. s, NH)
74.1
74.7
9b
3190
3360
2.28 (3Н, s, СН3); 7.16-7.41 (8Н, m, Нarom); 8.21 (1Н,
br. s, NH)
EXPERIMENTAL
1
The IR spectra were recorded on a UR-20 in KBr disks. The H NMR spectra were measured on a
Varian Gemini spectrometer (200 MHz) in CDCl3 solution, internal standard HMDS. The 19F NMR spectra were
obtained on a Bruker WP-200 (188 MHz) in CDCl3 solution, internal standard CCl3F. TLC was done on Silufol
UV-254 plates.
4-Nitrophenyl N-(1-Aryl-2,2,2-trifluoroethylidene)urethanes (1a,b). 4-Nitrophenol (1.39 g, 0.01 mol)
and triethylamine (1.01 g, 0.01 mol) were added to a solution of the corresponding 1-aryl-1-chloro-2,2,2-
trifluoroethyl isocyanate [5] (0.01 mol) in benzene (45 ml). The mixture was stirred at room temperature for 2 h.
The triethylamine hydrochloride precipitate was filtered out, the filtrate was refluxed for 1 h, the solvent was
evaporated, and the residue was recrystallized from a 1:3 hexane–benzene mixture.
1
Compound 1a. Yield 85%; mp 73-74°C. IR spectrum, ν, cm-1: 1790 (C=O), 1720 (C=N). H NMR
spectrum, δ, ppm: 7.96-8.09 (4H, m, C6H4); 7.49-7.60 (5H, m, C6H5). 19F NMR spectrum, δ, ppm: 69.23 s.
Found, %: C 53.16; H 2.59; N 8.34. C15H9F3N2O4. Calculated, %: C 53.27; H 2.68; N 8.28.
243

1
Compound 1b. Yield 86%; mp 97-98°C. IR spectrum, ν, cm-1: 1800 (C=O), 1725 (C=O). H NMR
19
spectrum, δ, ppm: 7.41-8.03 (8H, m, C6H4); 2.29 (3H, s, CH3). F NMR spectrum, δ, ppm: 70.08 s. Found, %:
C 54.12; H 3.25; N 8.17. C16H11F3N2O4. Calculated, %: C 54.55; H 3.15; N 7.95.
3-Aryl-3-trifluoromethyl-3,4,7,8-tetrahydro-5H-imidazo[2,3-b]-1,3,5-thiadiazin-5-ones (7a,b), 4-Aryl-
4-trifluoromethyl-3,4-dihydro-2H-1,5,3-(benzo)oxathiazepin-2-ones (8a,b, 9a,b). Triethylamine (4-5 drops)
was added to a mixture of N-alkylideneurethane 1a,b (0.005 mol) and the nucleophilic reagent 2-4 (0.005 mol)
in benzene (50 ml), and the mixture was heated at the boiling point for 3 h. After the solvent was evaporated, the
residue was washed with a saturated solution of Na2CO3 (50 ml), dried, and purified by crystallization.
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1.
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4.
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