C- and N-amidotrichloroethylation of azoles

Article abstract of DOI:10.1023/A:1020957711438

1H-Pyrazoles, triazoles, and imidazoles in reaction with ethoxycarbonylimine and arylsulfonylimines of chloral yield addition products, corresponding 1-(1-amidotrichloroethyl)azoles. Derivatives of 1-alkylpyrazoles and pyrazolones react with chloral 4-chl

Full text of DOI:10.1023/A:1020957711438

Russian Journal of Organic Chemistry, Vol. 38, No. 8, 2002, pp. 1178 1182. From Zhurnal Organicheskoi Khimii, Vol. 38, No. 8, 2002,
pp. 1230 1234.
Original English Text Copyright
2002 by Evstafyeva, Bozhenkov, Aizina, Rozenzveig, Ermakova, Levkovskaya, Mirskova.
*
C- and N-Amidotrichloroethylation of Azoles
I. T. Evstafyeva, G. V. Bozhenkov, Ya. A. Aizina, I. B. Rozenzveig,
T. G. Ermakova, G. G. Levkovskaya, and A. N. Mirskova
Faworsky Irkutsk Institute of Chemistry, Irkutsk, 664033 Russia
Received February 8, 2002
Abstract 1H-Pyrazoles, triazoles, and imidazoles in reaction with ethoxycarbonylimine and arylsulfonyl-
imines of chloral yield addition products, corresponding 1-(1-amidotrichloroethyl)azoles. Derivatives of
1
-alkylpyrazoles and pyrazolones react with chloral 4-chlorophenylsulfonylimine to furnish products of
C-amidotrichloroethylation into position 4 of the azole ring.
In the framework of systematic research on amido-
alkylating efficiency of acyl- and sulfonylimines of
polyhaloaldehydes we succeeded formerly in perform-
ing amidoalkylation on a series of O-, S-, and
N-containing heterocycles [1 5]. Among the latter
several pyrroles [4], and also indole and its C- and
N-methyl-substituted derivatives were used for amido-
alkylation [5]. In these cases the reaction occurred
without catalyst, did not require heating, and resulted
in products of C-trichloroamidoalkylation of pyrroles
in the position 2, and indoles in the position 3.
of azole nucleophilic addition at the activated C=N
bond (Table 1). A similar product was also obtained
in reaction of chloral ethoxycarbonylimine with
triazole II.
In the series of di- and triazoles up till now the
amidoalkylation was not studied save the example
described [6] of reaction between 1-alkyl(aryl)-3-alkyl-
(
phenyl)pyrazol-5-ones and ethoxycarbonyl-, acetyl-,
and benzoylimines of chloral that resulted in amido-
trichoroethylation in the position 4 of the pyrazolone
ring.
1
2
3
1
I, R = SO C H Cl, R = H, XR = N; II, R =
2
2
6
4
3
1
In extension of systematic investigation on
reactivity, in particular in the amidoalkylation reac-
tion, of acyl- and arylsulfonylimines of polyhalo-
aldehydes prepared from N,N-dichloroamides and
polyhaloethenes [7] we studied chloral trichloroethyl-
idenearenesulfonamides and ethoxycarbonylimine in
reactions with a series of azoles: benzimidazole,
OCOC H , R = H, XR = N; III, R = SO C H Cl,
R = CH , XR = C CH ; IV, R = SO C H Cl,
XR = CH, V, R = SO C H Cl, XR = C CH ;
VI, R = C H Cl, XR = N; VII, R =SO C H ,
2
5
2
6
4
2
3
1
3
3
2
6
4
4
1
4
2
6
4
3
1
4
1
6
4
2
6
5
4
XR = N.
The structure of compounds synthesized was
established from the IR and H NMR spectra
(Table 2), and the composition was confirmed by
elemental analysis (Table 1).
1
2
3
-methylbenzimidazole,
,5-dimethylpyrazole, and also with N-methyl-sub-
stituted pyrazole and 1-heptyl-3-methylpyrazol-5-one.
triazole,
benzotriazole,
It was established that reaction of chloral aryl-
sulfonylimines with benzimidazole, 2-methylbenz-
imidazole, triazole, benzotriazole, and 3,5-dimethyl-
pyrazole provided in high yield the products I, III VI
In the IR spectra of nucleophilic addition products
I VII are present strong absorption bands of sulfonyl
group, of alkyl and aryl CH bonds, and of NH group
1
(Table 2). The H NMR spectra of compounds from
triazole series I, II, VI, VII contain doublet signals
from protons of CH and NH groups with coupling
constants of 9 10 Hz (Table 2). At the same time in
the spectra of pyrazole and imidazole derivatives
*
The study was carried out underfinancial support of the
Committee of the Russian Academy of Sciences for support of
young scientists (grant no. 158/1999).
1
070-4280/02/3808-1178$27.00 2002 MAIK Nauka/Interperiodica

C- AND N-AMIDOTRICHLOROETHYLATION OF AZOLES
Table 1. Yields, melting points, and elemental analyses of compounds I X
1179
Found, %
Cl
Calculated, %
Cl
Compd. Yield,
mo p,
C
Formula
no.
%
C
H
N
S
C
H
N
S
I
70 172 175 29.37 2.26 38.46 14.85 7.35 C H Cl N O S 30.7 2.07 36.36 14.36 8.22
10 8 4 2 2
II
80 135 137 28.74 3.43 37.58 17.73
C H Cl N O
29.24 3.15 36.99 19.49
7
9
3
4
2
III
IV
V
89 128 130 36.57 3.14 34.24 9.45 7.57 C H Cl N O S 37.43 3.14 34.69 10.07 7.69
1
3
13
4
3
2
72 130 135 42.81 2.72 33.04 9.61 7.56 C H Cl N O S 41.03 2.52 32.45 9.57 7.30
1
5
11
4
3
2
87 84 85
42.93 2.70 32.12 9.67 7.52 C H Cl N O S 42.60 2.46 31.44 9.31 7.11
1
6
13
4
3
2
VI
VII
VIII
IX
70 189 190 37.84 2.24 33.24 12.74 6.78 C H Cl N O S 38.21 2.29 32.22 12.7 7.27
1
4
11
4
4
3
71 164 166 41.25 2.89 28.22 13.49 8.23 C H Cl N O S 41.45 2.73 26.22 13.81 7.90
1
4
12
3
4
2
71 198 200 39.64 3.75 32.55 9.68 8.21 C H Cl N O S 39.16 3.52 33.33 9.79 7.45
1
4
15
4
3
2
40 218 220 45.17 4.39 30.21 8.96 6.89 C H Cl N O S 44.63 4.54 29.29 8.68 6.61
1
9
24
4
3
3
(
compounds III V) no splitting of CH and NH
3-methylpyrazol-5-one: The reaction gave rise to a
product of 4-amidotrichloroethylation in the pyrazole
ring IX. The use of boron trifluoride etherate here
and in reaction of 1,3,5-trimethylpyrazole did not
reduce the process time, but decreased the yield of
the target products (compounds VIII and IX).
resonances is observed, and these proton signals
appear as individual considerably broadened singlets
(
Table 2). The proton signals from the para-substitut-
ed aromatic rings are observed in the spectra of com-
pounds I, III VI, VIII, IX as two doublets cor-
responding to AA BB spin system. In the spectra of
1
1
compounds VI and VII the signals of the aromatic
protons and those of the benzotriazole fragment are
overlapped; the latter signals appear as three
multiplets. In the spectrum of compound IV the
protons of benzimidazole fragment give three groups
of signals of equal intensity, and therewith in the
spectrum are seen two doublets belonging to the
protons of the para-substituted aromatic ring
(Table 2).
It should be noted that compounds I VII are easily
hydrolyzed in the presence of water and at heating
affording the initial azole and 1-hydroxy-2,2,2-tri-
chloroethylamides that have been isolated and char-
acterized before [8]. This instability of products
I VII against water was already observed at register-
1
ing H NMR spectra in DMSO at heating to 50 C.
5
Here alongside the signals. e.g., of azole I, arose the
proton peaks from 1-hydroxy-2,2,2-trichloroethyl-
amide [8].
R = CH (VIII), C H (IX).
3
7
15
Thus we demonstrated that arylsulfonyl- and
ethoxycarbonylimines of chloral under mild condi-
tions reacted with triazoles, imidazoles, and 1H-pyr-
azole affording in high yield products of nucleophilic
addition to the C=N bond. It was also established
that N-alkyl-substituted pyrazoles and pyrazolones in
reaction with chloral 4-chlorophenylsulfonylimine
furnished products of C-amidoalkylation in the 4
position of the heterocycle. These reactions require
more stringent conditions than the previously studied
C-amidoalkylation of pyrroles and indoles.
It was demonstrated that 1,3,5-trimethylpyrazole
reacted with chloral 4-chlorophenylsulfonylimine at
heating to 80 C for 20 h without catalyst or in the
presence of boron trifluoride etherate yielding up to
7
0% of a product of C-amidoalkylation in the 4
position of the pyrazole ring (compound VIII)
(Table 1).
Similarly occurred the reaction between trichloro-
ethylidene(4-chlorobenzene)sulfonamide and 1-heptyl-
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 38 No. 8 2002

1
Table 2. IR and H NMR spectra of compounds I IX
1
1
Compd.
IR spectrum, , cm
H NMR spectra, , ppm (J, Hz)
SO (C=O) CH alc CH arom
NH
CH3
2.24
N CH3
CH-CCl3
5.21 e (9.2)
6.89 e (9.6)
H asol
8.46
C H X
NH
Solvent
2
6
4
I
1170
340
1710
2720
2860
2780
3090
3130
3130
3230
3170
7.57 e, 7.91 e
(AA BB )
8.99 e
(CD ) CO
3
2
1
1
1
a
II
8.35
1.20 t, 4.12 q
9.29 e (9.6) DMSO-d6,
2
2
920
970
III
IV
1160
2920
2950
3070
3090
3310
3260
5.61
5.04
5.82
7.53 e, 7.29 e
(AA BB )
6.64
8.25
CDCl3
1340
1
1
2970
1170
350
2720
2850
3060
3100
7.58 (2H)
7.45 (1H)
7.82 e, 7.64 e
(AA BB )
DMSO-d6
1
1
1
2970
7.20
(2H)
V
1190
320
1190
360
1180
350
1150
320
1180
330
2610
2750
2720
3310
3330
3250
2.64
3.58
5.05
5.20 e (9.2)
5.22 e (9.2)
5.58
6.94
7.20
7.92
7.83 e, 7.65 e
(AA BB )
7.91
9.04 e (9.2)
8.92 e (9.2)
5.73
DMSO-d6
DMSO-d6
DMSO-d6
CDCl3
1
1
1
VI
3060
3080
3070
3100
3050
3080
3060
3090
7.67 e, 7.44 e
(AA BB )
1
1
1
b
VII
VIII
IX
2620
3850
2930
7.44
7.92, 7.60 m
1
3270
2.08
3260
2.24
2.10
7.35 e, 7.56 e
(AA BB )
1
1
1
c
2860
2920
3.50 t
5.35 e (8.8) 5.00 (8.8)
4.80
7.84 e, 7.47 e
(AA BB
CDCl3
1
1
1
2950
d
IX
1180
330
2860
2920
3060
3090
3260
2.03 3.43 T
7.70 e, 7.48 e
(AA BB )
DMSO-d6
1
1
1
2950
a
The spectrum of the ethyl group from the ethoxycarbonyl fragment og compound II is reported.
The spectrum of C H group of compound VII is given.
b
c
6
5
The chemical shift of N CH group from the fragment N CH (CH ) CH is reported; the order signals of the fragment are sa follows (CDCl , , ppm):
2
2
2 5
3
3
1
.6 m (CH ); 1.24 m (CH ) ; 1.93 m (CH ).
2
2 4
3
The chemical shift of N CH group from the fragment N CH (CH ) CH is reported in the spectrum recorded in DMSO-d . The order signals ( , ppm) are
d
2
2
2 5
3
6
0
.56 m (CH ), 1.27 m (CH ) .
3
2 5

C- AND N-AMIDOTRICHLOROETHYLATION OF AZOLES
1181
EXPERIMENTAL
amide, 13.1 g (0.1 mol) of anhydrous trichloroethyl-
ene, and 1.18 g (0.01 mol) of benzimidazole in
anhydrous benzene. We obtained 3.20 g of com-
pound IV.
1H NMR spectra were registered on spectrometers
Bruker DPX-400 (400 Mhz) and Jeol FX-90 Q
(
90 MHz) in organic solutions of 5 10% concentra-
N-[1-(2-Methylbenzimidazol-1-yl)-2,2,2-trichloro-
ethyl]-4-chlorobenzenesulfonamide (V) was syn-
thesized similarly to compound I from trichloro-
tion, internal reference HMDS.
IR spectra were recorded on spectrophotometer
Specord 75IR from KBr pellets.
ethylidene(4-chlorobenzene)sulfonamide
prepared
from 2.60 g (0.01 mol) of N,N-dichloro(4-chloro-
benzene)sulfonamide and 13.1 g (0.1 mol) of
anhydrous trichloroethylene, and 1.32 g (0.01 mol) of
methylbenzimidazole. We obtained 3.03 g (67%) of
compound V.
Imidazoles and triazoles used in the work were
purified by recrystallization. 1,3,5-Trimethylpyrazole
was obtained from 3,5-dimethylpyrazole and methyl
iodide. 1-Heptyl-3-methylpyrazol-5-one was prepared
from methyl acetoacetate and heptylhydrazine [9].
The imines used were obtained from acids dichloro-
amides and trichloroethylene [10, 11].
N-[1-(Benzotriazol-1-yl)-2,2,2-trichloroethyl]-4-
chlorobenzenesulfonamide (VI) was synthesized
similarly to compound I from trichloroethylidene(4-
chlorobenzene)sulfonamide prepared from 2.60 g
N-[1-(1,2,4-Triazol-2-yl)-2,2,2-trichloroethyl]-4-
chlorobenzenesulfonamide (I). A mixture of 2.60 g
(
0.01 mol) of N,N-dichloro(4-chlorobenzene)sulfon-
(
0.01 mol) of N,N-dichloro(4-chlorobenzene)sulfon-
amide and 13.1 g (0.1 mol) of anhydrous trichloro-
ethylene, and 1.20 g (0.01 mol) of benzotriazole in
anhydrous benzene. We obtained 3.08 g of compound
VI.
amide and 13.1 g (0.1 mol) of trichloroethylene was
boiled at 85 90 C under continuous bubbling of
argon. The reaction was carried out for 8 9 h till the
end of chlorine liberation (test with iodo-starch paper).
Then trichloroethylene was distilled off in a vacuum,
the residue was dissolved in 10 ml of anhydrous
chloroform, and 0.69 g (0.01 mol) of 1,2,4-triazole
was added. The mixture was stirred at room tempera-
ture for 3 4 h. The formed colorless precipitate was
filtered off, washed with anhydrous chloroform, and
dried. We obtained 2.71 g of compound I.
N-[1-(Benzotriazol-1-yl)-2,2,2-trichloroethyl]-4-
benzenesulfonamide (VII) was synthesized similarly
to compound I from trichloroethylidenebenzene-
sulfonamide prepared from 2.14 g (0.01 mol) of
N,N-benzenesulfonamide and 13.1 g (0.1 mol) of
anhydrous trichloroethylene, and 1.20 g (0.01 mol)
of benzotriazole in anhydrous benzene. We obtained
2
.62 g of compound VII.
N-[1-(1,2,4-Triazol-2-yl)-2,2,2-trichloroethyl]-
ethoxycarbonylamine (II). To 1.13 g (0.01 mol) of
N-(2, 2, 2-trichloroethylidene)ethoxycarboxamide
prepared from N,N-dichlorourethane and trichloro-
ethylene [11] was added 10 ml of anhydrous carbon
tetrachloride and 0.69 g (0.01 mol) of 1,2,4-triazole,
and the mixture was stirred at room temperature for
N-[1-(1,3,5-Trimethylpyrazol-4-yl)-2,2,2-tri-
chloroethyl]-4-chlorobenzenesulfonamide (VIII).
To trichloroethylidene(4-chlorobenzene)sulfonamide
prepared from 2.60 g (0.01 mol) of N,N-dichloro(4-
chlorobenzene)sulfonamide and 13.1 g (0.1 mol) of
trichloroethylene after excess trichloroethylene was
distilled off in a vacuum was added 1.1 g (0.01 mol)
of 1,3,5-trimethylpyrazole and 15 ml of anhydrous
benzene. The mixture was heated to 80 C for 15
5
h. We obtained 2.55 g of compound II.
N-[1-(3,5-Dimethylpyrazol-1-yl)-2,2,2-trichloro-
ethyl]-4-chlorobenzenesulfonamide (III). The pre-
paration procedure was similar to the synthesis of
compound I. From 2.60 g (0.01 mol) of N,N-dichloro-
2
0h, then it was cooled, and hexane or petroleum
ether was added thereto. The separated precipitate
was filtered off, dried, and recrystallized from
ethanol. We obtained 3.07 g of compound VIII.
(
4-chlorobenzene)sulfonamide, 13.1 g (0.1 mol)
of trichloroethylene, and 0.96 g (0.01 mol) of
,5-dimethylpyrazole (the second stage was carried
1
-Heptyl-3-methyl-4-[(4-chlorobenzenesulfon-
3
amido)-2,2,2-trichloroethyl]pyrazol-5-one (IX) was
obtained in a similar way as compound VIII from
trichloroethylidene(4-chlorobenzene)sulfonamide
prepared from 2.60 g (0.01 mol) of N,N-dichloro(4-
chlorobenzene)sulfonamide and 13.1 g (0.1 mol) of
trichloroethylene, and 1.96 g (0.01 mol) of 1-heptyl-
3-methylpyrazol-5 one synthesized analogously to [9].
Yield 2.04 g.
out in anhydrous benzene) was obtained 3.67 g of
compound III.
N-[1-(Benzimidazol-1-yl)-2,2,2-trichloroethyl]-4-
chlorobenzenesulfonamide (IV) was synthesized
similarly to compound I from trichloroethylidene(4-
chlorobenzene)sulfonamide prepared from 2.60 g
(
0.01 mol) of N,N-dichloro(4-chlorobenzene)sulfon-
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 38 No. 8 2002

1
182
EVSTAFYEVA et al.
6. Sicker, D., Behlmann, W., Bender, D., and
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5
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