Nucleophilic substitution in the series of (1,2,3-triazol-1-yl)-1,2,5- oxadiazoles. Reactions with N-, O-, and S-nucleophiles

Article abstract of DOI:10.1007/s11172-006-0059-8

Methods for the synthesis of amino(1,2,3-triazol-1-yl)-1,2,5-oxadiazoles (aminotriazolylfurazans) with CH₂Cl and COCH₂Br substituents in the triazole ring were developed and nucleophilic substitution for their halogen atom in reactio

Full text of DOI:10.1007/s11172-006-0059-8

Russian Chemical Bulletin, International Edition, Vol. 54, No. 8, pp. 1923—1934, August, 2005
1923
Nucleophilic substitution in the series of (1,2,3ꢀtriazolꢀ1ꢀyl)ꢀ1,2,5ꢀoxadiazoles.
Reactions with Nꢀ, Oꢀ, and Sꢀnucleophiles
V. Yu. Rozhkov, L. V. Batog,ꢀ and M. I. Struchkova
N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences,
47 Leninsky prosp., 119991 Moscow, Russian Federation.
Fax: +7 (495) 135 5328. Eꢀmail: mnn@ioc.ac.ru
Methods for the synthesis of amino(1,2,3ꢀtriazolꢀ1ꢀyl)ꢀ1,2,5ꢀoxadiazoles (aminoꢀ
triazolylfurazans) with CH2Cl and COCH2Br substituents in the triazole ring were developed
and nucleophilic substitution for their halogen atom in reactions with Nꢀ, Oꢀ, and Sꢀnucleoꢀ
philes were studied. The possibility of displacing the NO2 group from the furazan and triazole
rings in triazolylfurazans by an azido group was investigated. Novel compounds of this series
were synthesized; the reaction rate and pathway were found to depend on the nature of the
substrate and the reagent and the position of the substituent in isomers.
Key words: (1,2,3ꢀtriazolꢀ1ꢀyl)ꢀ1,2,5ꢀoxadiazoles; nucleophilic substitution; chloromethyl,
bromoacetyl, and nitro derivatives; aminoazidofurazan; amines; thiols; thiourea; thioacetamide.
The chemistry of 1,2,3ꢀtriazoles and 1,2,5ꢀoxadiazoles
(furazans) have been much investigated. Derivatives of
these heterocycles attract the attention of researchers as
possible starting material for preparation of novel energyꢀ
rich and biologically active compounds.1—4 A possible
route to compounds of these series with desired substituꢀ
ents is provided by nucleophilic substitution reactions.
For instance, reactions of nitrofurazans with Oꢀ and
Sꢀnucleophiles have been studied5,6 and substitution of
the N3 group for chlorine in the CH2Cl substituent in the
1,2,3ꢀtriazole ring has been reported.7
Earlier,8—11 we have developed methods for the synꢀ
thesis of (1,2,3ꢀtriazolꢀ1ꢀyl)ꢀ1,2,5ꢀoxadiazoles, in which
the triazole and furazan rings are linked by the N(1´)—C
bond. Some reactions of these compounds (e.g., oxidaꢀ
tion of the NH2 group at the furazan ring into NO2, NO,
and N=N groups and transformation of the NH2 group
into an N3 group via diazotization) were investigated.12
The first example of nucleophilic substitution in triꢀ
azolylfurazans was displacement of the nitro group at the
furazan ring in 4ꢀnitroꢀ3ꢀ(4ꢀphenylꢀ1Hꢀ1,2,3ꢀtriazolꢀ1ꢀ
yl)ꢀ1,2,5ꢀoxadiazole by an amino group in a reaction with
morpholine.12
tained revealed that some of them are promising as selecꢀ
tive inhibitors of kinaseꢀ3 of glycogen synthase (GSKꢀ3).
The present study was devoted to nucleophilic substiꢀ
tution for some functional substituents in both rings of
triazolylfurazans. Substitution for the NO2 groups in the
nitrofurazan and nitrotriazole fragments of triazolylꢀ
furazans 1a,b and for the chlorine and bromine atoms in
the CH2Cl and BrCH2CO substituents at the triazole ring
in compounds 2—4 was studied in the presence of various
nucleophiles. Additional goals were to substantially exꢀ
tend the range of substituted triazolylfurazans and eluciꢀ
date the effects of both heterocycles and the nature and
position of the substituents on the reactivities of the corꢀ
responding functional groups.
Comꢀ
R1
R2
Comꢀ
R1
R2
Recently,13 new representatives of triazolylfurazans
have been obtained by reactions of aminoazidofurazan
with ethyl chloroacetoacetate, also with the use of
Nꢀnucleophiles such as hydrazine and secondary amines
(dimethylamine, diethylamine, isobutylamine, pyrroꢀ
lidine, and piperidine). Information on the preparation of
the starting chloromethyl substrate in the individual
state and its physicochemical characteristics are lacking.
A study13 of the biological activity of the compounds obꢀ
pound
pound
1a
1b
2a
2b
2c
H
CH2OH
H
H
CH2Cl
H
3a
3b
3c
4
CO2Et
CO2Me
CO2Pri
CH2Cl
CH2Cl
CH2Cl
Me
NO2
CH2Cl
H
C(O)CH2Br
NO2
Nitro compounds 1a,b and 2c and chloromethyl deꢀ
rivatives 2a,b have been synthesized earlier.8,9,12 Triꢀ
azolylfurazans 3a—c and 4 have not been described. The
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 8, pp. 1866—1876, August, 2005.
1066ꢀ5285/05/5408ꢀ1923 © 2005 Springer Science+Business Media, Inc.

1924
Russ.Chem.Bull., Int.Ed., Vol. 54, No. 8, August, 2005
Rozhkov et al.
Scheme 1
Scheme 2
8: R1 = H, R2 = CH2OH (a); R1 = NO2, R2 = H (b)
of bromine in AcOH on product 7 prepared by cycloaddiꢀ
tion of azide 5 to acetylacetone10 (see Scheme 1).
The structures of halo derivatives 3a—c and 4 were
proved by H and 13C NMR and IR spectroscopy, mass
1
6: R1 = CH2OH, R2 = H (a); R1 = H, R2 = CH2OH (b)
spectrometry, and elemental analysis (Tables 1—3).
To obtain azides from nitro compounds 1a and 1b and
chloro derivatives 3a—c, we studied their reactions with
NaN3. The reactions of compounds 1a and 1b with NaN3
were carried out in MeCN and AcOH (1a). It turned out
that the reaction in AcOH virtually does not occur; in
MeCN, the nitro group at the furazan ring was successꢀ
fully replaced by an azido group to give the corresponding
azides 8a and 8b (Scheme 2). The nitro group in the
triazole ring of compound 1b remained intact. Azide 8b
was identified from Rf and the IR spectrum with an auꢀ
thentic sample synthesized12 by diazotization of the corꢀ
responding amine followed by treatment of the diazoꢀ
nium ion with NaN3. The structure of azide 8a was proved
by elemental analysis and spectroscopic studies (see
Tables 1—3). Refluxing of compound 2c containing, in
contrast to dinitro derivative 1b, the NO2 group only in
synthesis of chlorides 2a,b by cycloaddition of 4ꢀaminoꢀ
3ꢀazidofurazan (5) to propargyl chloride8 allowed only
one isomer (2a) to be isolated in good yield; for this
reason, we employed here an alternative method of preꢀ
paring compound 2b. A reaction of the corresponding
5ꢀhydroxymethyl derivative 6b (obtained from azide 5
and propargyl alcohol) with SOCl2 in CHCl3 in the presꢀ
ence of pyridine (the conditions used for similar transforꢀ
mations in 1,2,3ꢀtriazoles14) gave isomer 2b in high yield
(Scheme 1). Chlorination of 4ꢀhydroxymethyl derivaꢀ
tive 6a (see Ref. 8) under the same conditions was also
efficient. Compounds 3a—c were synthesized by reacꢀ
tions of 4ꢀaminoꢀ3ꢀazidofurazan15 (5) with the correꢀ
sponding alkyl chloroacetoacetates as described earlier10
(see Scheme 1). Compound 4 was obtained by the action
Table 1. Selected physicochemical characteristics of the compounds obtained
Comꢀ Yield
pound (%)
(method)
M.p./°C
(solvent)
Rf
(eluent)
Found
Calculated
Molecular
formula
(%)
С
H
N
Hal
S
3a
3b
3c
4
83 (A)
90 (B)
76
125—126
(EtOH)
134—135
(МеОH)
91—92
(PriOH)
170—171
(MeOH)
59—62 (α)
79—81 (β)
0.39
(PhH—AcOEt, 5 : 1)
0.38
(РhH—AcOEt, 5 : 1)
0.44
(PhH—AcOEt, 5 : 1)
0.68
(PhH—AcOEt, 5 : 1)
0.36
35.48
35.24
33.04
32.51
38.01
37.71
29.52
29.29
29.10
28.86
3.18
3.33
2.83
2.73
4.03
3.87
2.53
2.46
1.85
1.92
30.51
13.29
13.00
14.29
13.71
12.11
12.37
27.64
27.83
—
—
С8H9СlN6O3
C7H7ClN6O3
C9H11ClN6O3
C7H7BrN6O2
С5H4N8О2
30.82
31.99
32.50
29.04
29.32
29.59
29.27
54.03
53.84
—
—
—
—
81
86
79
8a
(CH2Cl2—AcOEt, 3 : 1)
(to be continued)

Nucleophilic substitution in the triazolylfurazan series Russ.Chem.Bull., Int.Ed., Vol. 54, No. 8, August, 2005
Table 1 (continued)
1925
Comꢀ Yield
pound (%)
(method)
M.p./°C
(solvent)
Rf
(eluent)
Found
Calculated
Molecular
formula
(%)
С
H
N
Hal
—
S
9
68
90
97
80
86
83
210—211
(acetone)
90—94
(EtOH)
105—106
0.60
35.87
35.96
28.78
28.99
28.83
28.99
34.59
34.41
31.46
31.70
36.98
36.86
3.45
3.40
2.60
2.41
2.30
2.41
3.18
3.25
2.58
2.66
3.91
3.78
36.50
—
C8H9N7O4
C5H5N9O
C5H5N9O
C8H9N9O3
C7H7N9O3
C9H11N9O3
(PhH—AcOEt, 3 : 1)
36.69
61.10
60.86
61.25
60.86
45.48
45.15
47.93
47.54
43.32
42.99
10a
10b
11a
11b
11c
0.76
(CH2Cl2—AcOEt, 3 : 1)
0.66
(CH2Cl2—AcOEt, 3 : 1)
0.39
(PhH—AcOEt, 5 : 1)
0.33
(PhH—AcOEt, 5 : 1)
0.60
—
—
—
—
—
—
—
—
—
—
81—82
(EtOH)
115—116
(MeOH)
117—118
(acetone—H2О, (PhH—AcOEt, 5 : 1)
1 : 1)
12a
12b
12c
12d
12e
12f
12g
12h
14
96
87
94
88
89
97
75
90
85
68
93.5
83
82
83
97
95
87
76
161—162
(EtOH)
156—157
(EtOH)
115—116
(EtOH)
122—123
(EtOH)
140—141
(ЕtОH)
161—162
0.12
44.81
44.58
50.37
50.14
48.54
48.85
49.03
48.85
42.41
42.47
53.97
54.08
54.31
54.26
48.78
48.59
29.53
29.46
50.78
50.91
38.05
38.16
46.54
46.63
46.64
46.51
44.78
44.66
45.07
44.95
36.53
36.61
37.83
37.94
43.37
43.24
36.21
36.36
45.16
45.05
5.41
5.30
6.42
6.31
5.98
5.89
5.74
5.89
5.11
5.05
4.74
4.82
5.52
5.57
6.14
5.96
2.14
2.06
4.36
4.27
4.02
3.91
3.74
3.65
3.29
3.38
3.34
3.25
3.87
3.77
3.03
3.07
3.51
3.58
3.21
3.33
3.18
3.05
5.23
5.15
30.67
30.33
29.67
29.24
24.55
24.92
24.61
24.92
28.61
28.89
27.40
27.59
28.31
28.12
30.18
30.51
34.57
34.36
25.69
25.44
29.96
29.67
29.35
29.00
25.19
25.31
24.69
24.30
28.44
28.23
33.47
33.21
33.02
33.19
29.68
29.41
42.57
42.40
33.87
33.43
—
—
—
—
—
—
—
—
—
—
—
—
—
—
C12H17N7O4
C14H21N7O3
C16H23N7O5
C16H23N7O5
(PhH—AcOEt, 5 : 1)
0.36
(PhH—AcOEt, 5 : 1)
0.30
(PhH—AcOEt, 5 : 1)
0.16
(PhH—AcOEt, 5 : 1)
—
9.29
9.45
—
С12H17N7O3S
C16H17N7O3
C18H22N8O3
C13H19N7O3
C6H5ClN6O3
C14H14N6O4
C18H22N12O6S2
С15H14N8O3S
C15H13N7O4S
C15H13N7O3S2
C13H13N7O3S
C9H9N7O3S
0.43
(PhH—AcOEt, 5 : 1)
207—208
(EtOH)
139—140
0.27
—
—
(PhH—AcOEt, 5 : 1)
0.53
(PhH—AcOEt, 1 : 1)
183—184
(decomp.)
101—102
(EtOH)
211—212
(EtOH)
232—233
(EtOH)
127—128
(EtOH)
149—150
(EtOH)
145—146
(EtOH)
143—144
(EtOH)
191—192
0.58
(MeOH)
0.56
14.57
14.49
—
15
(PhH—AcOEt, 5 : 1)
—
18a
18b
18c
18d
18e
18f
18g
18h
20
—
—
—
—
—
—
—
—
—
—
11.24
11.32
8.21
8.30
8.36
8.28
16.01
15.83
9.40
9.23
10.94
10.86
6.04
6.33
9.48
9.62
11.97
12.13
—
0.16
(PhH—AcOEt, 5 : 1)
0.52
(PhH—AcOEt, 5 : 1)
0.58
(PhH—AcOEt, 5 : 1)
0.40
(PhH—AcOEt, 5 : 1)
0.39
(PhH—AcOEt, 5 : 1)
0.20
(PhH—AcOEt, 3 : 1)
0.31
C16H18N12O6S
C12H11N7O3S
C8H8N8OS
170—171
(MeOH)
(PhH—AcOEt, 5 : 1)
0.79
87 266—267 (decomp.)
(acetone)
98
(AcOEt)
0.35
(AcOEt)
21
193—194
C11H15N7O3

1926
Russ.Chem.Bull., Int.Ed., Vol. 54, No. 8, August, 2005
Rozhkov et al.
Table 2. 1H and 13C NMR spectra of the compounds obtained
Comꢀ
pound
NMR, δ (J/Hz)
1H
13C
3a
1.44 (t, 3 H, Me, J = 7.4); 4.02 (s, 2 H, CH2Cl);
4.50 (q, 2 H, СH2O, J = 7.4); 6.41 (s, 2 H, NH2)
3.96 (s, 3 H, MeO); 5.17 (s, 2 H, CH2);
6.75 (s, 2 H, NH2)
13.91 (Me); 31.50 (CH2Cl); 61.59 (CH2O); 138.82 (C(3));
139.90 (C(5´)); 141.83 (C(4´)); 152.40 (CNH2); 159.52 (CO)
31.52 (Me); 52.73 (CH2Cl); 136.69; 140.15; 141.95;
152.47 (CNH2); 160.16 (CO)
3b
3c
1.44 (d, 6 H, 2 Me, J = 6.6); 5.14 (s, 2 H, CH2);
5.30 (sept, 1 H, CH, J = 5.3); 6.60 (s, 2 H, NH2)
2.68 (s, 3 H, Mе); 4.87 (s, 2 H, CH2);
6.67 (s, 2 H, NH2)
21.45 (Me); 31.47 (CH2Cl); 69.56 (CH); 137.10; 139.79;
141.85; 152.38 (CNH2); 158.99 (CO)
9.49 (Me); 65.80 (CH2); 140.25; 140.60; 140.66; 142.23;
152.49 (CNH2); 194.04 (CO)
4
8a
4.76 (s, 2 H, CH2); 5.90 (s, 1 H, OH);
7.90 (s, 1 H, CH)
52.96 (CH2); 132.98; 141.45; 144.73; 149.73
9
3.10 (br.s, 4 H, (СH2)2О); 3.60 (br.s, 4 H,
(СH2)2N); 9.90 (s, 1 H, C(5´)H)
47.46 (CH2N); 65.05 (CH2O); 128.04; 142.67;
153.69 (CNO2); 154.56
10a
10b
11a
11b
11c
4.52 (s, 2 H, CH2); 5.69 (s, 2 H, NH2);
8.45 (s, 1 H, CH)
4.82 (s, 2 H, CH2); 5.69 (s, 2 H, NH2);
7.85 (s, 1 H, CH)
1.38 (t, 3 H, Me, J = 7.1); 4.45 (q, 2 H, CH2О,
J = 7.1); 4.99 (s, 2 H, CH2); 6.69 (s, 2 H, NH2)
3.96 (s, 3 H, OMe); 5.00 (s, 2 H, CH2N3);
6.70 (s, 2 H, NH2)
1.34 (d, 6 H, 2 Ме, J = 6.6); 4.94 (s, 2 H,
C(5´)CH2); 5.25 (sept, 1 H, CH, J = 5.3);
6.71 (s, 2 H, NH2)
44.13 (CH2); 124.36 (C(5´)H); 143.19 (C(4´));
144.71 (C(3)); 151.15 (CNH2)
42.77 (CH2); 134.12 (C(4´)H); 135.30 (C(5´));
142.50 (C(3)); 151.75 (CNH2)
13.99 (Me); 41.65 (CH2); 61.50 (CH2O); 137.18 (C(4´));
138.86 (C(5´)); 142.05 (C(3)); 152.51(CNH2); 159.67 (CO)
41.60 (CH2N3); 52.36 (MeO); 137.00 (C(4´)); 138.89 (C(5´));
142.03 (C(3)); 152.41 (CNH2); 160.14 (CO)
21.43 (Me); 41.65 (CH2N3); 69.52 (CMe2); 137.53 (C(4´));
138.58 (C(3)); 142.09 (C(5´)); 152.54 (CNH2);
159.24 (CO)
12a
12b
1.37 (t, 3 H, Me, J = 7.2); 2.30 (s, 4 H,
CH2ОCH2); 3.34 (s, 4 H, (CH2NCH2);
4.00 (s, 2 H, C(5´)CH2); 4.41 (q, 2 H, MeCH2O,
J = 7.2); 6.54 (s, 2 H, NH2)
0.75 (m, 2 H, СH2); 0.80 (d, 3 H, Me, J = 6.4);
1.23 (m, 1 H, СH); 1.35 (q, 3 H, Me, J = 7.1);
1.42 (m, 2 H, СH2); 1.98 (t, 2 H, СH2, J = 10.9);
2.52 (m, 2 H, СH2); 3.99 (s, 2 H, CH2);
4.40 (q, 2 H, СH2, J = 7.1); 6.58 (s, 2 H, NH2)
1.17, 1.36 (both t, 3 H each, Me, J = 7.0);
1.24, 2.12 (both m, 2 H each, СH2); 1.52, 1.77, 2.02,
14.10 (Me); 49.91 (C(5´)CH2); 52.73 (CH2N);
61.07 (MeCH2O); 65.78 (CH2O); 136.90 (C(4´));
142.54 (C(5´)); 143.54 (C(3)); 153.54 (CNH2);
160.26 (CO)
14.10 (MeCH2O); 21.57 (Me); 29.44 (CH); 33.44 (CH2);
39.51 (CH2N); 50.15; 52.95; 60.94 (CH2O); 136.45 (C(4´));
143.24 (C(5´)); 143.52 (C(3)); 153.37 (CNH2); 160.20 (CO)
12c
12d
13.99, 14.10 (Me); 23.77; 26.11; 39.81; 40.81 (CH); 49.87;
52.72; 54.45; 59.84 (CH2O); 61.03 (CH2O); 136.69 (C(4´));
2.52, 2.78 (all m, 1 H each, СH); 4.04 (m, 4 H, 2 СH2); 142.80 (C(5´)); 143.38 (C(3)); 153.35 (CNH2);
4.40 (q, 2 H, СH2, J = 7.0); 6.60 (s, 2 H, NH2)
1.19, 1.38 (both t, 3 H each, Me, J = 7.1); 1.25, 1.64,
2.07, 2.55 (all m, 2 H each, СH2); 2.17 (m, 1 H, СH);
160.18 (C(4´)CO); 172.75 (CO)
13.81, 13.86 (Me); 27.23; 39.40 (CH); 49.68; 51.79;
59.50 (CH2O); 60.77 (CH2O); 136.55 (C(4´)); 142.64 (C(5´));
3.98 (s, 2 H, CH2); 4.04, 4.40 (both q, 2 H each, СH2, 143.27 (C(3)); 153.14 (CNH2); 160.05 (C(4´)CO);
J = 7.1); 6.56 (s, 2 H, NH2)
173.71 (CO)
12e
12f
1.35 (t, 3 H, Ме, J = 7.1); 2.34, 2.55 (both m,
4 H each, 4 CH2); 4.00 (s, 2 H, C(5´)CH2);
4.40 (q, 2 H, CH2O, J = 7.1); 6.50 (s, 2 H, NH2)
1.37 (t, 3 H, Ме, J = 7.1); 2.73, 3.13 (both t,
2 H each, СH2, J = 6.1); 4.45 (q, 2 H, СH2О,
J = 7.1); 4.77 (s, 2 H, C(5´)CH2); 6.43 (d, 1 H,
Ph, J = 8.0); 6.53 (s, 2 H, NH2); 6.68 (t, 1 H,
Ph, J = 8.0); 6.95 (m, 2 H, Ph)
14.00 (Me); 26.70 (CH2S); 50.40 (C(5´)CH2); 54.20 (CH2N);
61.00 (CH2O); 136.90 (C(5´)); 142.70 (C(4´)); 143.50 (C(3));
153.40 (CNH2);160.20 (CO)
14.10 (Me); 27.90 (C(3″)); 42.40 (C(5´)CH2); 53.70 (C(2″));
61.20 (CH2O); 107.10 (C(7″)); 118.00 (C(4″)); 124.20 (C(5″));
127.00 (C(6″)); 129.20 (C(3″а)); 136.60 (C(4´)); 142.60 (C(3));
142.90 (C(5´)); 150.70 (C(7″а)); 153.00 (CNH2); 160.20 (CO)
12g
1.35 (t, 3 H, Me, J = 7.2); 2.50, 2.85 (both s,
4 H each, 4 СH2); 4.10 (s, 2 H, C(5´)CH2);
4.45 (q, 2 H, СH2О, J = 7.2); 6.50 (s, 2 H, NH2);
6.70 (t, 1 H, pꢀPh, J = 7.1); 6.85 (d, 2 H, oꢀPh,
J = 7.1); 7.20 (t, 2 H, mꢀPhH, J = 7.1)
14.00 (Ме); 47.70 (PhNCH2); 49.50 (C(5´)CH2);
52.10 (CH2CH2N); 60.90 (CH2O); 115.20 (oꢀPh);
118.80 (pꢀPh); 128.70 (mꢀPh); 136.70 (C(5´)); 142.60(C(3));
143.40 (C(4´)); 150.60 (CNH2); 153.40 (ipsoꢀPh); 160.20 (CO)
(to be continued)

Nucleophilic substitution in the triazolylfurazan series Russ.Chem.Bull., Int.Ed., Vol. 54, No. 8, August, 2005
Table 2 (continued)
1927
Comꢀ
pound
NMR, δ (J/Hz)
1H
13C
12h
1.30 (br.s, 6 H, 2 Me); 1.55, 2.40 (both m,
4 H each, 4 CH2); 4.20 (s, 2 H, C(5´)CH2);
5.25 (br.s, 1 H, CH); 6.60 (s, 2 H, NH2)
5.17 (s, 2 H, CH2); 6.77 (s, 2 H, NH2)
21.60 (Me); 23.18 (NCH2CH2); 46.50 (C(5´)CH2);
52.90 (NCH2); 68.70 (CH); 136.40 (C(4´)); 143.20 (C(3));
143.50 (C(5´)); 153.20 (CNH2); 159,70 (CO)
31.44 (CH2Cl); 137.49 (C(4´)); 139.60 (C(5´)); 141.83 (C(3));
152.30 (CNH2); 160.93 (CO)
14.00 (Me); 58.51 (C(5´)CH2); 61.44 (CH2O); 114.39 (oꢀPh);
121.86 (pꢀPh); 129.68 (mꢀPh); 136.90 (C(4´)); 140.08 (C(5´));
142.76 (C(3)); 152.92 (CNH2); 157.01 (ipsoꢀPh); 159.85 (CO)
14
15
1.33 (t, 3 H, Me, J = 7.1); 4.44 (q, 2 H, CH2O,
J = 7.1); 5.59 (s, 2 H, C(5´)CH2); 6.60 (s, 2 H,
NH2); 6.89 (d, 2 H, Ph, J = 8.1); 6.98 (t, 1 H, Ph,
J = 7.2); 7.30 (t, 2 H, Ph, J = 7.8)
18a
18b
1.35 (t, 6 H, 2 Me, J = 7.0); 2.65 (s, 4 H,
CH2CH2); 4.28 (s, 4 H, 2 C(5´)CH2); 4.38 (q, 4 H,
2 CH2O, J = 7.0); 6.62 (s, 4 H, 2 NH2)
1.36 (t, 3 H, Me, J = 7.4); 4.36 (q, 2 H, CH2O,
J = 7.4); 4.97 (s, 2 H, CH2S); 6.62 (s, 2 H, NH2);
7.10, 7.35 (both m, 2 H each, Ph); 12.50 (s, 1 H, NH)
13.81 (Me); 22.13 (C(5´)CH2); 30.93 (SCH2CH2S);
61.08 (CH2O); 136.05 (C(4´)); 141.89 (C(3)); 142.10 (C(5´));
152.21 (CNH2); 159.93 (CO)
13.92 (Me), 23.42 (CH2S); 61.22 (CH2O); 110.42,
117.67 (CPh—N); 121.28, 121.96 (CPh); 137.06 (C(4´));
141.70 (C(5´)); 142.50 (C(3)); 147.62 (CAr—S);
152.55 (CNH2); 159.80 (CO)
18c
18d
1.35 (t, 3 H, Me, J = 7.4); 4.45 (q, 2 H, CH2O,
J = 7.4); 5.05 (s, 2 H, CH2S); 6.70 (br.s, 2 H,
NH2); 7.30, 7.55 (both m, 2 H each, Ar)
13.97 (Me); 23.70 (CH2S); 61.39 (CH2O); 110.10, 118.40,
124.57, 124.69 (CPh); 137.32 (C(4´)); 140.85 (C(5´));
142.50 (C(3)); 146.64, 151.46 (CPh); 152.70 (CNH2);
159.79 (CO); 162.25 (CAr—S)
1.30 (t, 3 H, Me, J = 7.4); 4.40 (q, 2 H, СH2O,
J = 7.4); 5.10 (s, 2 H, CH2S); 6.70 (br.s, 2 H,
NH2); 7.38, 7.45 (both t, 1 H each, Ph, J = 8.4);
7.70, 7.95 (both d, 1 H each, Ph, J = 9.1)
1.35 (t, 3 H, Me, J = 7.4); 4.40 (q, 2 H, CH2O,
J = 7.4); 4.90 (s, 2 H, CH2S); 6.70 (br.s, 2 H,
NH2); 7.10, 7.20, 7.60, 8.12 (all br.s, 1 H each, Py)
1.35 (t, 3 H, Me, J = 7.4); 4.40 (q, 2 H, СH2О,
J = 7.4); 4.90 (s, 2 H, CH2S); 6.70 (s, 2 H, NH2)
13.83 (Me); 24.22 (CH2S); 61.26 (CH2O); 121.06, 121.66,
124.77, 126.27 (Ph); 134.95 (CPh—S); 137.21 (C(4´));
140.96 (C(5´)); 142.23 (C(3)); 151.91 (CPh—N);
152.45 (CNH2); 159.72 (CO); 163.76 (CAr—S)
13.90 (Me); 21.00 (CH2S); 61.00 (CH2O); 120.30, 121.80 (Py);
136.70 (C(4´)); 142.30 (C(3)); 142.40 (C(5´)); 148.80 (Py);
152.50 (CNH2); 155.30 (CPy—S); 159.80 (CO)
13.80 (Me); 24.60 (CH2S); 61.50 (CH2O); 111.11 (CN);
137.20 (C(4´)); 138.70 (C(5´)); 141.80 (C(3)); 152.00 (CNH2);
159.40 (CO)
18e
18f
18g
18h
1.32 (br.s, 6 H, 2 Me); 4.35 (br.s, 8 H, 2 CH2;
2 CH2O); 6.69 (br.s, 4 H, 2 NH2)
13.87 (Me); 23.40 (CH2S); 61.18 (CH2O); 136.34 (C(4´));
141.01 (C(5´)); 141.95 (C(3)); 152.19 (CNH2); 159.83 (CO)
21.16 (C(5´)CH2); 52.41 (MeO); 120.50 (C(4″));
122.00 (C(5″)); 136.80 (C(4´)); 137.00 (C(3″)); 142.60 (C(3));
142.90 (C(5´)); 149.00 (C(6″)); 152.80 (CNH2);
155.70 (C(2″)S); 160.60 (CO)
9.57 (Me); 103.60 (CH); 132,05; 140.39; 141.40; 142.73;
152.16 (CNH2, furazan.); 168.94 (CNH2, thiazole.)
9.52 (Me); 53.11; 63.91; 66.16; 140.42; 141.75; 142.17;
152.34 (CNH2); 191.42 (CO)
3.96 (s, 3 H, МеО); 4.90 (s, 2 H, СH2S);
6.67 (s, 2 H, NH2); 7.06 (t, 1 H, С(5″)H, J = 6.1);
7.20 (d, 1 H, С(3″)H, J = 8.0); 7.60 (t, 1 H,
С(4″)H, J = 7.5); 8.16 (d, 1 H, С(6″)H, J = 4.0)
2.75 (s, 3 H, Me); 6.63 (s, 2 H, NH2 furazan.);
7.05 (s, 1 H, CH); 7.13 (s, 2 H, NH2 thiazole.)
2.57 (br.s, 4 H, СH2ОСH2); 2.68 (s, 3 H, Me);
3.61 (br.s, 4 H, (CH2)2N); 3.98 (s, 2 H, CH2CO);
6.65 (s, 2 H, NH2)
20
21
the triazole ring with NaN3 in MeCN recovered the startꢀ
ing compound.
in turn, the βꢀform was completely (or partially in benꢀ
zene) converted into the αꢀform upon refluxing in hexane
or heptane. The distinguishing absorption bands in the IR
spectra of the βꢀform appear at 1370, 1350, 1320, 980,
970, and 840 cm–1, while those for the αꢀform appear at
1450, 1430, 1305, 1280, and 1165 cm–1. The ability of
1,2,3ꢀtriazoles to exist in two forms was discovered16 for
methyl 5ꢀchloroꢀ1ꢀphenylꢀ1Hꢀ1,2,3ꢀtriazoleꢀ4ꢀcarbꢀ
oxylate.
It should be noted that azide 8a, like previously reꢀ
ported amino(triazolyl)furazans8,9 with the NO2 (2c) and
CH2OH groups (6a) in position 4 of the triazole ring,
yields two interconvertible forms arbitrarily denoted as α
(lowerꢀmelting, m.p. 59—62 °C) and β (higherꢀmelting,
m.p. 79—81 °C), depending on the solvent nature. Also,
the IR spectra of their crystalline samples are different.
Azide 8a obtained as the αꢀform was converted into the
βꢀform upon refluxing in CCl4, MeCN, or cyclohexane;
As noted earlier,12 the nitro group in 4ꢀnitroꢀ3ꢀ(4ꢀpheꢀ
nylꢀ1Hꢀ1,2,3ꢀtriazolꢀ1ꢀyl)ꢀ1,2,5ꢀoxadiazole is successꢀ

1928
Russ.Chem.Bull., Int.Ed., Vol. 54, No. 8, August, 2005
Rozhkov et al.
Table 3. IR and mass spectra of the compounds obtained
Comꢀ
pound
IR, ν/cm–1
MS, m/z (Irel (%))
3a
3440, 3345, 3060, 3000, 1750 (CO), 1650, 1570, 1540, 1480, 1460,
1390, 1355, 1310, 1280, 1260, 1180, 1100, 1060, 1020, 920,
880, 850, 820, 770, 730, 710
3400, 3300, 3000, 1752 (CO), 1632, 1572, 1452, 1260, 1160, 1112,
1032, 996, 872, 820, 728, 712
3430, 3335, 3055, 2985, 2935, 1740 (CO), 1635, 1580, 1565, 1450,
1385, 1300, 1270, 1150, 1100, 1030, 990, 872, 848, 728, 712
3408, 3312, 2944, 1704 (CO), 1644, 1600, 1553, 1408, 1384 1304,
1192, 1100, 972, 864, 736
272 [M]+ (23), 254 (9), 209 [M – N2 – Cl]+,
168 [M + 1 – EtO – N2 – NO]+ (34),
54 (100)
3b
3c
4
258 [M]+ (15), 228 (6), 200 (2), 194 (15),
49(100)
286 [M]+ (8), 227 [Mꢀ N2H – NO]+ (15),
181 (20), 150 (22), 43(100)
286 [M – 1]+ (21), 258 [M – 1 – N2]+
(16), 228 [258 – N2 –NO]+ (11),
201 (38), 165 (73), 149 (87), 67 (100)
—
8a
9
αꢀform: 3365, 3140, 2155 (N3), 1600, 1580, 1545, 1450, 1430,
1390, 1340, 1305, 1280, 1230, 1165, 1100, 1080, 1063, 1050, 985,
880, 790
βꢀform: 3340, 2165 (N3), 1600, 1580, 1545, 1440, 1400, 1370,
1350, 1320, 1185, 1120, 1090, 1075, 1060, 1035, 980, 970, 880, 840
3112 (CH triazole.), 2992, 2936, 2868, 1588, 1552, 1524, 1460,
1444, 1400, 1380, 1344, 1308, 1296, 1260, 1204, 1104, 1064,
1028, 980, 940, 832
267 [M]+ (10), 239 [M – N2]+ (29),
100 (100)
10a
10b
11a
11b
11c
3450, 3350, 3110, 2115 (N3), 1650, 1600, 1580, 1345, 1270, 1260,
1250, 1190, 1070, 1050, 985, 840, 780
3464, 3332, 3148, 2124 (N3), 1636, 1584, 1356, 1308, 1280, 1088,
1060, 976, 868, 856
3408, 3316, 2984, 2140 (N3), 2104 (N3), 2072, 1720 (CO), 1640,
1624, 1568, 1448, 1240, 1132, 1096, 1040, 968, 848
3416, 3316, 3020, 2964, 2880, 2144 (N3), 2112 (N3), 1724 (CO),
1636, 1584, 1452, 1248, 1132, 1040, 996, 972, 876, 800, 748
3460, 3324, 2988, 2176 (N3), 2140 (N3), 2112 (N3), 2080,
1736 (CO), 1628, 1588, 1568, 1452, 1388, 1288, 1248, 1220, 1184,
1096, 1040, 992, 964, 916, 848, 796, 756, 728
—
—
—
—
—
12a
12b
3452, 3272, 3228, 2980, 2960, 2944, 2872, 2832, 1728 (CO),
1632, 1588, 1568, 1454, 1360, 1280, 1260, 1228, 1216, 1132,
1104, 1072, 1040, 1004, 972, 916, 868, 812, 784
3452, 3272, 3104, 2978, 2932, 2856, 2784, 1728 (CO), 1628,
1592, 1568, 1452, 1308, 1264, 1248, 1228, 1216, 1128, 1104,
1044, 988, 860, 772
323 [M]+ (1), 278 (1), 100 (100),
86 (8), 56 (21)
335 [M]+ (1), 290 [M – EtO]+ (1),
134 (7), 112 (100)
12c
12d
3452, 3092, 2984, 2952, 2868, 2815, 1732 (CO), 1628, 1452, 1372,
1300, 1272, 1232, 1184, 1116, 1052, 1028, 988, 860, 812, 788
3452, 3090, 2984, 2948, 2820,1732 (CO), 1628, 1588, 1568,
1452, 1304, 1260, 1248, 1208, 1168, 1124, 1096, 1052, 1040,
988, 860, 776
393 [M]+ (1), 365 [M – N2]+ (1),
348 (3), 171 (11), 170 (100), 156 (24)
393 [M]+ (1), 348 [M – EtO]+ (7),
171 (13), 170 (100), 156 (24)
12e
12f
3448, 3180, 2976, 2820, 1724 (CO), 1628, 1584, 1568, 1452, 1380,
1292, 1240, 1196, 1132, 1104, 1036, 988, 952, 912, 848, 776
3464, 3336, 2972, 2936, 2864, 1732 (CO), 1628, 1584, 1564, 1484,
1444, 1376, 1300, 1252, 1208, 1128, 1092, 1040, 1016, 988, 868,
776, 752, 716
—
355 [M]+ (2), 168 (5), 167 (14),
132 (100), 118 (26)
12g
12h
14
3456, 3272, 3100, 2944, 2832, 1724 (CO), 1632, 1600, 1588, 1564,
1504, 1448, 1350, 1292, 1268, 1244, 1224, 1180, 1124, 1100, 1036,
984, 920, 856, 792, 756, 692
3468, 2976, 2844, 2804, 1716 (CO), 1632, 1568, 1444, 1376, 1308,
1248, 1232, 1132, 1096, 1036, 988, 912, 848
—
321 [M]+ (3), 293 [M – N2]+ (1),
262 [M – N2H – NO]+ (5), 236 (1),
203 (4), 84 (100)
244 [M]+ (50), 227 [M – OH]+ (4),
200 [M – CO2]+ (62), 44 (CO) (100)
3424, 3300, 2867, 2760, 2534, 1716 (CO), 1640, 1588, 1568, 1432,
1260, 1220, 1184, 1104 1032, 996, 892, 768
(to be continued)

Nucleophilic substitution in the triazolylfurazan series Russ.Chem.Bull., Int.Ed., Vol. 54, No. 8, August, 2005
Table 3 (continued)
1929
Comꢀ
pound
IR, ν/cm–1
MS, m/z (Irel (%))
15
3468, 3444, 2988, 1736 (CO), 1628, 1600, 1588, 1572, 1496, 1448,
1376, 1268, 1240, 1212, 1036, 984, 860, 844, 788, 752, 688
330 [M]+ (22.6), 301 [M – N2H]+ (1),
226 (45), 163 (53), 138 (52), 107 (91),
93 (14), 77 (Ph) (100)
18a
18b
3408, 3312, 2984, 1708 (CO), 1640, 1628, 1592, 1564, 1444, 1416,
1372, 1304, 1272, 1164, 1132, 1032, 988, 868, 848, 796, 716
3448, 3268, 3232, 2984, 1736 (CO), 1636, 1560, 1472, 1452, 1408,
1384, 1356, 1268, 1260, 1220, 1184, 1112, 1100, 1036, 1008, 992,
864, 848, 772, 756, 708
566 [M]+ (1), 329 (47), 301(52),
269 (48), 133 (100)
—
18c
3476, 3428, 3328, 2984, 1732 (CO), 1632, 1584, 1560, 1500, 1380,
1300, 1256, 1236, 1220, 1176, 1136, 1096, 1032, 988, 740
387 [M]+ (40), 359 [M – N2]+ (19),
329 [M – NO – N2]+ (12), 283 (12),
179 (10), 164 (35), 150 (73), 122 (100)
403 [M]+ (5), 375 (2), 302 (17),
167 (93), 148 (9), 134 (16), 108 (100)
—
18d
18e
3480, 3436, 2996, 1740 (CO), 1632, 1584, 1560, 1452, 1276, 1240,
1184, 1136, 1096, 1032, 988, 868, 848, 740
3412, 3312, 3040, 2992, 1740 (CO), 1624, 1556, 1456, 1416, 1384,
1268, 1240, 1224, 1188, 1128, 1088, 1032, 988, 872, 844, 796,
776, 724
3440, 3328, 3024, 3000, 2972, 2168 (CN), 1700 (CO), 1636, 1596,
1560, 1452, 1352, 1280, 1180, 1112, 1032, 984, 868, 848, 796, 716
3460, 3348, 2984, 1720 (CO), 1632, 1568, 1448, 1272, 1028, 988
18f
18g
18h
20
295 [M]+ (35), 250 [M – EtO]+ (7),
238 (2), 150 (100)
506 [M]+ (10), 269 (18), 238 (100),
210 (15), 163 (30), 98 (28)
—
3484, 3324, 2956, 1728 (CO), 1628, 1580, 1560, 1452, 1416, 1388,
1260, 1220, 1124, 1096, 1032, 988, 872, 788, 764, 716
3472, 3408, 3364, 3248, 3115, 1628, 1580, 1528, 1304, 1128,
976, 840
3440, 3284, 3240, 3196, 2972, 2932, 2864, 2808, 1700 (CO), 1632,
1588, 1556, 1452, 1408, 1388, 1296, 1212, 1176, 1112, 1088, 1036,
964, 920, 864, 776
264 [M]+ (19), 206 (50), 179 (80),
151 (70), 109 (81), 69 (100)
—
21
Scheme 3
fully replaced by the morpholine fragment. We demonꢀ
strated here that a reaction of dinitro compound 1b
with morpholine yields 4ꢀmorpholinofurazan (9) (see
Scheme 2, Tables 1—3).
We tried to convert isomeric compounds 2a and 2b
containing the CH2Cl group in positions 4 and 5, respecꢀ
tively, into azides 10a and 10b by a reaction with NaN3 in
boiling MeCN (Scheme 3). Monitoring of the reaction by
TLC was impossible because the retention factors (Rf) of
the reaction products and the starting chlorides were equal.
1
The course of the reaction was monitored by H NMR
Comꢀ
pound
R1
R2
H
CH2N3
CH2N3
CH2N3
CH2N3
spectroscopy. It was found that both isomers afford the
corresponding azido derivatives 10a and 10b in high yields;
the 4ꢀisomer 2a is more reactive than the 5ꢀisomer 2b,
which is evident from the times of the reaction completion.
Reactions of 5ꢀchloromethyl derivatives 3a—c with
NaN3 in boiling aqueous solutions of ethanol or acetone
gave the corresponding azides 11a—c (see Scheme 3,
Tables 1—3).
With the aim of obtaining 5ꢀaminomethyl derivatives
12 from compounds 3a—c, we studied reactions of the
latter with various heterocyclic amines 13.
Reactions of amines 13a—g (morpholine (13a),
4ꢀmethylpiperidine (13b), ethyl piperidineꢀ3ꢀ (13c)
10a
10b
11a
11b
11c
CH2N3
H
CO2Et
CO2Me
CO2Pri
and ꢀ4ꢀcarboxylates (13d), thiomorpholine (13e), indoꢀ
line (13f), and Nꢀphenylpiperazine (13g)) with compound
3a as an example were carried out with a slight excess of
the amine (1 : 1.3) in the presence of NaHCO3 (1 : 1.4) or
with a double excess of the amine (1 : 2.2) in the absence
of NaHCO3. Substitution products 12a—g were obtained

1930
Russ.Chem.Bull., Int.Ed., Vol. 54, No. 8, August, 2005
Rozhkov et al.
in good yields (Scheme 4). The reaction of chloromethyl
derivative 3c with pyrrolidine (13h) afforded product 12h
(see Scheme 4). The structures of compounds 12a—h
were proved by elemental analysis and spectroscopic studꢀ
ies (see Tables 1—3).
Hydrolysis of isomeric chlorides 2a and 2b, as well as
their mixtures, was carried out in boiling water or aqueous
0.1 N NaOH and 1 N NaHCO3. Both the isomers were
hydrolyzed completely in alkaline and bicarbonate soluꢀ
tions; in water, they behaved differently: the 4ꢀisomer was
hydrolyzed completely, while the 5ꢀisomer, only slightly.
The results obtained were used to find appropriate condiꢀ
tions for the preparation of hydroxymethyl derivatives 6a
and 6b in high yields (see Scheme 3). In the case of
chloride 2a, compound 6a was obtained as a mixture of
two crystalline αꢀ and βꢀforms8 or as either individual
form,8 depending on the hydrolysis conditions. For inꢀ
stance, hydrolysis of chloride 2a in NaHCO3 gave comꢀ
pound 6a as the αꢀ (72%) and βꢀforms (22%), while hydroꢀ
lysis in NaOH afforded only the βꢀform (78%).
Scheme 4
Attempted displacement of the Cl atom from comꢀ
pound 3b by the OH group in boiling water failed. In
a boiling aqueous solution of NaHCO3 used in an equiꢀ
molar amount, the ester group was hydrolyzed to give
acid 14 in high yield (see Scheme 4, Tables 1—3); its
decarboxylation in boiling AcOH yielded product 2b,
which was spectroscopically identical with an authentic
sample.8
A reaction of compound 3a with phenol in boiling
EtOH gave substitution product 15 (see Scheme 4,
Tables 1—3).
We studied reactions of chloromethyl derivative 3a
with thiols 16a—e (ethaneꢀ1,2ꢀdithiol (16a), benzimidꢀ
azoleꢀ2ꢀthiol (16b), benzoxazoleꢀ2ꢀthiol (16c), benzoꢀ
thiazoleꢀ2ꢀthiol (16d), and pyridineꢀ2ꢀthiol (16e)),
KSCN, and thioacetamide 17. The reactions with the
thiols and amide 17 were carried out in boiling EtOH
(3—6 h) in the presence of K2CO3 or NaHCO3. The
reagents were used in the following molar ratios:
Reagents
Ratio
3a : 16a : K2CO3
3a : 16b—d : K2CO3
3a : 16e : NaHCO3
3a : 17 : K2CO3
2.1 : 1.0 : 1.0
1.0 : 1.1 : 0.5
1.0 : 1.1 : 1.0
1.0 : 1.2 : 0.5
In the reaction with KSCN, its double excess was
used. The resulting substitution products 18a—g were obꢀ
tained in high yields (82—97%) (see Scheme 4). The forꢀ
mation of compound 18g involves two molecules of chloꢀ
ride 3a: one interacts with the thiol form of thioacetamide,
while the other, with their adduct; apparently, MeCN is
detached. In boiling MeOH, compound 18e underwent
transesterification to give compound 18h. Like known
diamines of the furazan series,17—19 diamines 18a and 18g
(see Scheme 4) are of interest as starting material for the
synthesis of the corresponding macrocyclic compounds
containing the N=N fragment.
An investigation of reactions of 4ꢀ and 5ꢀchloromethyl
derivatives 2a,b and 3a,b with Oꢀnucleophiles (in parꢀ
ticular, with water and phenol) revealed that the reactivꢀ
ity of the Cl atom depends on the position of the CH2Cl
group in the triazole ring, the nature of the reagent, and
the presence of the COOEt group (3a).
The reactivity of bromoacetyl derivative 4 toward
nucleophilic reagents were studied in reactions with

Nucleophilic substitution in the triazolylfurazan series Russ.Chem.Bull., Int.Ed., Vol. 54, No. 8, August, 2005
1931
morpholine (13a) and thiourea (19). It is known20,21 that
reactions of haloacetyltriazoles and ꢀfurazans with thioꢀ
urea give rise to an aminothiazole fragment. The reaction
of compound 4 with thiourea in acetone in the presence
of K2CO3 yielded diamine 20 containing a thiazole ring
(Scheme 5). The reaction of compound 4 with a double
excess of morpholine in boiling EtOH gave substitution
product 21 (see Scheme 5). The physicochemical characꢀ
teristics of compounds 18a—h, 20, and 21 are given in
Tables 1—3.
Experimental
The course of the reactions was monitored and the purity of
the compounds obtained was checked by TLC on Silufol UVꢀ254
plates (Czechoslovakia). IR spectra (pellets with KBr) were reꢀ
corded on URꢀ20 and Specord Mꢀ80 spectrometers. 13C and
1H NMR spectra (DMSOꢀd6) were recorded on Bruker WMꢀ250
(62.80 and 250 MHz, respectively), Bruker AMꢀ300 (75.5 and
300 MHz, respectively), and Bruker DRXꢀ500 spectrometers
(500 MHz (1H)). 13C and 1H chemical shifts were measured
with reference to DMSOꢀd6 (δ(13C) 39.50; δ(1H) 2.50). Mass
spectra were recorded on a Varian MAT CHꢀ6 instrument. Meltꢀ
ing points were determined on a Boetius hot stage.
Scheme 5
Synthesis of chloromethyl derivatives 2a,b and 3a—c.
Chlorination of hydroxymethyl derivatives 6a and 6b
3ꢀAminoꢀ4ꢀ(4ꢀchloromethylꢀ1Hꢀ1,2,3ꢀtriazolꢀ1ꢀyl)ꢀ1,2,5ꢀ
oxadiazole (2a). Pyridine (0.6 mL, 75 mmol) and freshly disꢀ
tilled SOCl2 (5 mL, 75 mmol) were added dropwise at 2—5 °C to
a suspension of compound 6a (0.85 g, 4.67 mmol) in CHCl3
(75 mL). The reaction mixture was stirred at room temperature
(~20 °C) for 1 h. The solvent was removed in vacuo and ice water
(100 mL) was added to the residue (oil with crystals). The preꢀ
cipitate was filtered off, washed with water, and dried in air to
give chloride 2a (0.87 g, 92.9%) (see Ref. 8).
3ꢀAminoꢀ4ꢀ(5ꢀchloromethylꢀ1Hꢀ1,2,3ꢀtriazolꢀ1ꢀyl)ꢀ1,2,5ꢀ
oxadiazole (2b). Pyridine (1.2 mL, 150 mmol) and freshly disꢀ
tilled SOCl2 (10 mL, 150 mmol) were added dropwise at 2—5 °C
to a suspension of compound 6b (1.71 g, 9.4 mmol) in CHCl3
(110 mL). Cooling was stopped and the reaction mixture was
stirred at ~20 °C for 5 h. The mixture still containing the starting
reagent was allowed to stand for 16 h; after one day, the solvent
was removed in vacuo. The residue was treated as described for
compound 2a to give chloride 2b (1.74 g, 92.5%) (see Ref. 8).
Ethyl 1ꢀ(4ꢀaminoꢀ1,2,5ꢀoxadiazolꢀ3ꢀyl)ꢀ5ꢀchloromethylꢀ1Hꢀ
1,2,3ꢀtriazoleꢀ4ꢀcarboxylate (3a). A. A solution of azide 5 (3.5 g,
27.8 mmol) (see Ref. 15) and ethyl chloroacetoacetate (4.57 g,
27.8 mmol) in acetone (20 mL) was stirred at ~20 °C for 1 h in
the presence of K2CO3 (0.5 g, 3.62 mmol). Then water (50 mL)
was added with stirring. The precipitate that formed was filtered
off and washed with water and ether. The yield of compound 3a
was 6.3 g.
B. A mixture of azide 5 (1 g, 7.93 mmol) (see Ref. 15), ethyl
chloroacetoacetate (1.39 g, 9.53 mmol), and MgCO3 (0.3 g,
3.57 mmol) in EtOH (50 mL) was refluxed for 3 h. The hot
solution was filtered to remove inorganic salts and then evapoꢀ
rated to dryness. The residue was washed with water and ether.
The yield of compound 3a was 1.96 g.
Methyl 1ꢀ(4ꢀaminoꢀ1,2,5ꢀoxadiazolꢀ3ꢀyl)ꢀ5ꢀchloromethylꢀ
1Hꢀ1,2,3ꢀtriazoleꢀ4ꢀcarboxylate (3b). The reaction of azide 5
(2.47 g, 19.6 mmol) (see Ref. 15) with methyl chloroacetoacetate
(2.95 g, 19.6 mmol) was carried out in acetone (20 mL) in the
presence of K2CO3 (0.2 g, 1.45 mmol) by analogy with the
synthesis of compound 3a (A). The yield of chloride 3b was 3.85 g.
Isopropyl 1ꢀ(4ꢀaminoꢀ1,2,5ꢀoxadiazolꢀ3ꢀyl)ꢀ5ꢀchloromethylꢀ
1Hꢀ1,2,3ꢀtriazoleꢀ4ꢀcarboxylate (3c). The reaction of azide 5
(1 g, 7.93 mmol) (see Ref. 15) with isopropyl chloroacetoacetate
(1.7 g, 9.52 mmol) was carried out in acetone (10 mL) in the
The 1H NMR spectra of the compounds obtained (see
Table 2) show signals at δ 5.7—6.8 for the NH2 group
bound to the furazan ring and at δ 4.0—5.6 for the CH2
group in the CH2R substituents to the triazole ring; for
triazolylfurazans with the COOEt group, signals for the
CH2O fragment and the Me group appear at δ 4.4—4.5
and 1.4—1.5, respectively. The 13C NMR spectra of the
compounds bearing the ester and oxo groups show signals
for the carbonyl group at δ 159.3—160.6 and 191.5—194.1,
respectively. In the IR spectra of these compounds,
the absorption bands of the carbonyl group appear at
1700—1755 cm–1
.
Thus, in the present study, we obtained novel triazolylꢀ
furazans with the COCH2Br and CH2Cl groups in the
triazole ring by 1,3ꢀdipolar cycloaddition of aminoꢀ
azidofurazan to acetylacetone followed by bromination of
the reaction product or to alkyl chloroacetoacetates. The
reactions of these compounds and earlier synthesized
hydroxymethyl and nitro derivatives with Nꢀ, Sꢀ, and
Oꢀnucleophiles afforded a large number of substituted
triazolylfurazans, which are promising for use in further
transformations.

1932
Russ.Chem.Bull., Int.Ed., Vol. 54, No. 8, August, 2005
Rozhkov et al.
presence of K2CO3 (0.3 g, 2.17 mmol) by analogy with the
synthesis of compound 3a (A). The yield of compound 3c
was 1.85 g.
1ꢀ[1ꢀ(4ꢀAminoꢀ1,2,5ꢀoxadiazolꢀ3ꢀyl)ꢀ5ꢀmethylꢀ1Hꢀ1,2,3ꢀ
triazolꢀ4ꢀyl]ꢀ2ꢀbromoethanone (4). A solution of Br2 (0.77 g,
4.81 mmol) in AcOH (10 mL) was added at 5—10 °C to a stirred
solution of ketone 7 (1 g, 4.81 mmol) (see Ref. 10) in glacial
AcOH (25 mL). After 30 min, water (10 mL) was added dropwise.
The precipitate that formed was filtered off, washed with water,
and dried in air to give compound 4 (1.19 g).
ride 3c (0.19 g, 0.66 mmol) and NaN3 as described for comꢀ
pound 11b. The yield of azide 11c was 0.16 g.
Reactions of compound 3a with amines 13a—g
Synthesis of amino derivatives 12a—f. A mixture of comꢀ
pound 3a (1 g, 3.67 mmol) with a double excess of the correꢀ
sponding amine (13a—f) was refluxed in EtOH (30 mL) for 3
to 8 h. Water (30 mL) was added at ~20 °C and the precipitate
that formed was filtered off and washed with water and cold
ether to give ethyl 1ꢀ(4ꢀaminoꢀ1,2,5ꢀoxadiazolꢀ3ꢀyl)ꢀ5ꢀmorphoꢀ
linomethylꢀ1Hꢀ1,2,3ꢀtriazoleꢀ4ꢀcarboxylate (12a) (1.13 g), ethyl
1ꢀ(4ꢀaminoꢀ1,2,5ꢀoxadiazolꢀ3ꢀyl)ꢀ5ꢀ(4ꢀmethylpiperidinomethyl)ꢀ
1Hꢀ1,2,3ꢀtriazoleꢀ4ꢀcarboxylate (12b) (1.07 g), ethyl 1ꢀ(4ꢀamiꢀ
noꢀ1,2,5ꢀoxadiazolꢀ3ꢀyl)ꢀ5ꢀ(3ꢀethoxycarbonylpiperidinomethyl)ꢀ
1Hꢀ1,2,3ꢀtriazoleꢀ4ꢀcarboxylate (12c) (1.35 g), ethyl
1ꢀ(4ꢀaminoꢀ1,2,5ꢀoxadiazolꢀ3ꢀyl)ꢀ5ꢀ(4ꢀethoxycarbonylpiperiꢀ
dinomethyl)ꢀ1Hꢀ1,2,3ꢀtriazoleꢀ4ꢀcarboxylate (12d) (1.27 g), ethyl
1ꢀ(4ꢀaminoꢀ1,2,5ꢀoxadiazolꢀ3ꢀyl)ꢀ5ꢀthiomorpholinomethylꢀ
1Hꢀ1,2,3ꢀtriazoleꢀ4ꢀcarboxylate (12e) (1.21 g), and ethyl
1ꢀ(4ꢀaminoꢀ1,2,5ꢀoxadiazolꢀ3ꢀyl)ꢀ5ꢀindolinomethylꢀ1Hꢀ1,2,3ꢀ
triazoleꢀ4ꢀcarboxylate (12f) (1.26 g).
Reactions of nitro derivatives 1a and 1b with NaN3
1ꢀ(4ꢀAzidoꢀ1,2,5ꢀoxadiazolꢀ3ꢀyl)ꢀ1Hꢀ1,2,3ꢀtriazolꢀ5ꢀylꢀ
methanol (8a). Sodium azide (0.48 g, 7.36 mmol) was added at
~20 °C to a stirred solution of nitro compound 1a (0.78 g,
3.68 mmol) in MeCN (30 mL). After the starting reagent was
consumed completely (TLC data), the inorganic precipitate was
filtered off and the filtrate was evaporated to dryness in vacuo.
The yield of azide 8a (αꢀform8) was 0.6 g.
4ꢀAzidoꢀ3ꢀ(4ꢀnitroꢀ1Hꢀ1,2,3ꢀtriazolꢀ1ꢀyl)ꢀ1,2,5ꢀoxadiazole
(8b) was obtained from dinitro derivative 1b and NaN3 as deꢀ
scribed for compound 8a (see Ref. 12).
Ethyl
1ꢀ(4ꢀaminoꢀ1,2,5ꢀoxadiazolꢀ3ꢀyl)ꢀ5ꢀ(4ꢀphenylꢀ
Reaction of compound 1b with morpholine. 5ꢀMorpholinoꢀ4ꢀ
(4ꢀnitroꢀ1Hꢀ1,2,3ꢀtriazolꢀ1ꢀyl)ꢀ1,2,5ꢀoxadiazole (9). A solution
of morpholine (1.53 g, 17.6 mmol) in benzene (30 mL) was
added dropwise for 2 h to a stirred solution of compound 1b (1 g,
4.4 mmol) in benzene (50 mL). After 2 h, the precipitate was
filtered off, the mother liquor was evaporated to dryness, and
the solid residue was washed with water and dried in air to give
compound 9 (0.8 g).
piperazinꢀ1ꢀyl)methylꢀ1Hꢀ1,2,3ꢀtriazoleꢀ4ꢀcarboxylate (12g).
A mixture of chloromethyl derivative 3a (1 g, 3.67 mmol),
amine 13g (6.5 g, 4 mmol), and NaHCO3 (3.1 g, 3.69 mmol)
was refluxed in EtOH (20 mL) for 5 h. Water (10 mL) was added
to the hot solution and the mixture was kept for 16 h. The
precipitate that formed was filtered off, washed with water, and
dried in air to give compound 12g (1.1 g).
Reaction of chloromethyl derivative 3c with pyrrolidine 13h
Reactions of compounds 2a and 2b with NaN3
Isopropyl 1ꢀ(4ꢀaminoꢀ1,2,5ꢀoxadiazolꢀ3ꢀyl)ꢀ5ꢀpyrrolidinoꢀ
methylꢀ1Hꢀ1,2,3ꢀtriazoleꢀ4ꢀcarboxylate (12h). A mixture of
compound 3c (1 g, 3.49 mmol) and pyrrolidine (13h) (0.55 g,
7.68 mmol) was refluxed in PriOH (20 mL) for 1 h and then
treated as described for compound 12g. The yield of ester 12h
was 1.01 g.
3ꢀAminoꢀ4ꢀ(4ꢀazidomethylꢀ1Hꢀ1,2,3ꢀtriazolꢀ1ꢀyl)ꢀ1,2,5ꢀ
oxadiazole (10a). A mixture of compound 2a (0.1 g, 0.5 mmol)
and NaN3 (0.1 g, 1.53 mmol) in MeCN (10 mL) was refluxed
for 1 h. The precipitate was filtered off and the mother liquor
was concentrated in vacuo. The oily residue that crystallized in air
was washed with water and dried in air to give azide 10a (0.09 g).
3ꢀAminoꢀ4ꢀ(5ꢀazidomethylꢀ1Hꢀ1,2,3ꢀtriazolꢀ1ꢀyl)ꢀ1,2,5ꢀ
oxadiazole (10b). A mixture of compound 2b (0.3 g, 1.5 mmol)
and NaN3 (0.20 g, 3 mmol) in MeCN (20 mL) was refluxed
for 4 h. The precipitate was filtered off, the mother liquor was
evaporated to dryness in vacuo, and the residue was washed with
water and dried in air to give azide 10b (0.29 g).
Reactions of compounds 2a,b and 3a,b with Oꢀnucleophiles
Hydrolysis of 4ꢀchloromethyl derivative 2a. 1ꢀ(4ꢀAminoꢀ
1,2,5ꢀoxadiazolꢀ3ꢀyl)ꢀ1Hꢀ1,2,3ꢀtriazolꢀ4ꢀylmethanol (6a).
A. A suspension of chloride 2a (0.2 g, 1 mmol) in 1 N NaHCO3
(30 mL) was refluxed for 30 min. After three days, hydroxymethyl
derivative 6a (0.13 g, 72%) was filtered off in the αꢀform.8 Orꢀ
ganic material was extracted from the filtrate with AcOEt. The
extract was dried with MgSO4 and evaporated to dryness in vacuo
to give compound 6a (0.04 g, 22%) in the βꢀform.8 The total
yield of compound 6a was 0.17 g (94%).
B. A suspension of compound 2a (0.1 g, 0.5 mmol) in 0.1 N
NaOH (15 mL) was refluxed for 10 min. The reaction mixture
was cooled to ~20 °C and acidified with conc. HCl to pH 1. The
product was extracted with AcOEt to give compound 6a (0.07 g,
78%) in the βꢀform.8
Reactions of compounds 3a—c with NaN3
Ethyl 1ꢀ(4ꢀaminoꢀ1,2,5ꢀoxadiazolꢀ3ꢀyl)ꢀ5ꢀazidomethylꢀ1Hꢀ
1,2,3ꢀtriazoleꢀ4ꢀcarboxylate (11a). A solution of compound 3a
(0.5 g, 1.83 mmol) and NaN3 (0.14 g, 2.2 mmol) in EtOH—H2O
(1 : 1, 30 mL) was refluxed for 2 h. The precipitate that formed
at room temperature was filtered off and washed with water to
give azide 11a (0.41 g).
Methyl 1ꢀ(4ꢀaminoꢀ1,2,5ꢀoxadiazolꢀ3ꢀyl)ꢀ5ꢀazidomethylꢀ
1Hꢀ1,2,3ꢀtriazoleꢀ4ꢀcarboxylate (11b). A solution of comꢀ
pound 3b (0.5 g, 1.93 mmol) and NaN3 (0.15 g, 2.3 mmol) in
acetone—water (1 : 1) was refluxed for 2 h. Water (30 mL) was
added without cooling the mixture. The precipitate that formed
was filtered off and washed with water to give azide 11b (0.44 g).
Isopropyl 1ꢀ(4ꢀaminoꢀ1,2,5ꢀoxadiazolꢀ3ꢀyl)ꢀ5ꢀazidomethylꢀ
1Hꢀ1,2,3ꢀtriazoleꢀ4ꢀcarboxylate (11c) was obtained from chloꢀ
Hydrolysis of 5ꢀchloromethyl derivative 2b. 1ꢀ(4ꢀAminoꢀ
1,2,5ꢀoxadiazolꢀ3ꢀyl)ꢀ1Hꢀ1,2,3ꢀtriazolꢀ5ꢀylmethanol (6b). A susꢀ
pension of chloride 2b (0.1 g, 0.5 mmol) in 1 N NaHCO3 (10 mL)
was refluxed for 30 min. The precipitate that formed was filtered
off at ~20 °C to give compound 6b (0.08 g, 88%).
Hydrolysis of chloromethyl derivative 3b. 1ꢀ(4ꢀAminoꢀ1,2,5ꢀ
oxadiazolꢀ3ꢀyl)ꢀ5ꢀchloromethylꢀ1Hꢀ1,2,3ꢀtriazoleꢀ4ꢀcarboxylic

Nucleophilic substitution in the triazolylfurazan series Russ.Chem.Bull., Int.Ed., Vol. 54, No. 8, August, 2005
1933
acid (14). A suspension of compound 3b (0.5 g, 1.93 mmol) and
NaHCO3 (0.16 g, 1.93 mmol) in water (30 mL) was refluxed for
1 h to complete dissolution. The reaction mixture was acidified
at ~20 °C with 18% HCl to pH 2. The precipitate was filtered
off, washed with water, and dried in air to give acid 14 (0.40 g).
Decarboxylation of compound 14. A solution of compound 14
(0.2 g, 0.82 mmol) in AcOH (10 mL) was refluxed for 2 h. The
solvent was removed and the residue was washed with water to
give chloride 2b (0.14 g, 86%) (see Ref. 8).
Reaction of chloromethyl derivative 3a with phenol. Ethyl
1ꢀ(4ꢀaminoꢀ1,2,5ꢀoxadiazolꢀ3ꢀyl)ꢀ5ꢀphenoxymethylꢀ1Hꢀ1,2,3ꢀ
triazoleꢀ4ꢀcarboxylate (15). A solution of chloride 3a (1 g,
3.67 mmol) and phenol (0.41 g, 4.4 mmol) was refluxed in
EtOH (25 mL) in the presence of K2CO3 (0.25 g, 1.84 mmol)
for 5 h. The solvent was removed in vacuo and the residue was
recrystallized from EtOH to give compound 15 (0.82 g).
Water (20 mL) was added at ~20 °C and the precipitate was
filtered off and dried in air to give compound 18g (0.71 g).
Reactions of bromoacetyl derivative 4 with nucleophiles
4ꢀAminoꢀ3ꢀ[4ꢀ(2ꢀaminothiazolꢀ4ꢀyl)ꢀ5ꢀmethylꢀ1Hꢀ1,2,3ꢀ
triazolꢀ1ꢀyl]ꢀ1,2,5ꢀoxadiazole (20). A mixture of compound 4
(0.6 g, 2.09 mmol), thiourea (19) (0.17 g, 2.2 mmol), and K2CO3
(0.14 g, 1.05 mmol) was refluxed in acetone (20 mL) for 30 min.
The precipitate was filtered off, washed with cold water, and
dried in air to give compound 20 (0.48 g).
1ꢀ[1ꢀ(4ꢀAminoꢀ1,2,5ꢀoxadiazolꢀ3ꢀyl)ꢀ5ꢀmethylꢀ1Hꢀ1,2,3ꢀ
triazolꢀ4ꢀyl]ꢀ2ꢀmorpholinoethanone (21). A mixture of comꢀ
pound 4 (0.5 g, 1.74 mmol) and morpholine (0.33 g, 3.80 mmol)
was refluxed in EtOH (10 mL) for 5 min. After 2 to 3 h, the
precipitate that formed was filtered off, washed with EtOH and
ether, and dried in air to give compound 21 (0.5 g).
Reactions of compound 3a with Sꢀnucleophiles (16)
Synthesis of 1,2ꢀbis[1ꢀ(4ꢀaminoꢀ1,2,5ꢀoxadiazolꢀ3ꢀyl)ꢀ4ꢀ
ethoxycarbonylꢀ1Hꢀ1,2,3ꢀtriazolꢀ4ꢀylmethylthio]ethane (18a).
A mixture of compound 3a (0.41 g, 1.5 mmol), ethaneꢀ1,2ꢀ
dithiol (16a) (0.07 g, 7.1 mmol), and K2CO3 (0.21 g, 1.52 mmol)
was refluxed in EtOH (10 mL) for 5 h. The precipitate that
formed was filtered off at room temperature and washed with
water to give diamine 18a (0.40 g).
Compounds 18b—d. A mixture of compound 3a (1 g,
3.67 mmol), the corresponding thiol (16b—d), and K2CO3 in
the molar ratio 1 : 1.1 : 0.5 was refluxed in EtOH (30 mL)
for 5 (16b,c) or 6 h (16d). Water (15 mL) was added to the warm
solution (16b) or to the reaction mixtures at room temperature
(16c,d). The precipitate that formed was filtered off, washed
with cold water, and dried in air to give ethyl [1ꢀ(4ꢀaminoꢀ
1,2,5ꢀoxadiazolꢀ3ꢀyl)ꢀ5ꢀbenzimidazolꢀ2ꢀylthiomethyl]ꢀ1Hꢀ1,2,3ꢀ
triazoleꢀ4ꢀcarboxylate (18b) (1.18 g), ethyl [1ꢀ(4ꢀaminoꢀ1,2,5ꢀ
oxadiazolꢀ3ꢀyl)ꢀ5ꢀbenzoxazolꢀ2ꢀylthiomethyl]ꢀ1Hꢀ1,2,3ꢀ
triazoleꢀ4ꢀcarboxylate (18c) (1.16 g), and ethyl [1ꢀ(4ꢀaminoꢀ
1,2,5ꢀoxadiazolꢀ3ꢀyl)ꢀ5ꢀbenzothiazolꢀ2ꢀylthiomethyl]ꢀ1Hꢀ1,2,3ꢀ
triazoleꢀ4ꢀcarboxylate (18d) (1.22 g).
Ethyl (18e) and methyl [1ꢀ(4ꢀaminoꢀ1,2,5ꢀoxadiazolꢀ3ꢀyl)ꢀ
5ꢀpyridinꢀ2ꢀylthiomethyl]ꢀ1Hꢀ1,2,3ꢀtriazoleꢀ4ꢀcarboxylate
(18h). A mixture of compound 3a (1.1 g, 4.04 mmol), thiol 16e
(0.50 g, 4.5 mmol), and NaHCO3 (0.35 g, 4.17 mmol) was
refluxed in EtOH (20 mL) for 3 h. Water (10 mL) was added to
the stirred hot solution and the precipitate that formed was
filtered off at ~20 °C, washed with water, and dried in air. The
yield of compound 18e was 1.45 g. The whole amount of this
compound was refluxed in MeOH (40 mL) for 30 min and then
cooled to room temperature. The precipitate that formed was
filtered off to give compound 18h (1.19 g).
Ethyl [1ꢀ(4ꢀaminoꢀ1,2,5ꢀoxadiazolꢀ3ꢀyl)ꢀ5ꢀthiocyanatoꢀ
methyl]ꢀ1Hꢀ1,2,3ꢀtriazoleꢀ4ꢀcarboxylate (18f). A solution of
chloride 3a (1.32 g, 4.84 mmol) and KSCN (0.7 g, 7.22 mmol)
in EtOH (20 mL) was refluxed for 8 h and then concentrated to
a quarter of its original volume. The precipitate that formed
was washed with water and dried in air to give thiocyanꢀ
ate 18f (1.36 g).
References
1. R. Bohm and Cr. Karov, Pharmazie, 1981, 4, 243.
2. I. A. Abdugafurov, N. Madikhanov, A. G. Makhsumov,
Kh. M. Shakhidoyatov, A. A. Muzaffarov, A. U. Zokirov,
and Sh. S. Masharipova, Azotistye geterotsikly i alkaloidy
[Nitrogen Heterocycles and Alkaloids], Eds V. G. Kartsev and
G. A. Tolstikov, IridiumꢀPress, Moscow, 2001, 2, 8 (in
Russian).
3. V. G. Andrianov and A. V. Eremeev, Khim. Geterotsikl.
Soedin., 1984, 1155 [Chem. Heterocycl. Compd., 1984 (Engl.
Transl.)].
4. P. Sauerberg, P. H. Olesen, S. Nielsen, S. Treppendahl,
M. J. Sheardown, T. Honore, C. H. Mitch, J. S. Ward, A. J.
Pike, F. P. Bymaster, B. D. Sawyer, and H. E. Shannon,
J. Med. Chem., 1992, 35, 2274.
5. A. B. Sheremetev, O. V. Kharitonova, E. V. Mantseva,
V. O. Kulagina, E. V. Shatunova, N. S. Aleksandrova,
T. M. Mel´nikova, E. A. Ivanova, D. E. Dmitriev, V. E.
Eman, I. L. Yudin, V. S. Kuz´min, Yu. A. Strelenko, T. S.
Novikova, O. V. Lebedev, and L. I. Khmel´nitskii, Zh. Org.
Khim., 1999, 35, 1555 [Russ. J. Org. Chem., 1999, 35 (Engl.
Transl.)].
6. A. B. Sheremetev, E. V. Mantseva, N. S. Aleksandrova, V. S.
Kuz´min, and L. I. Khmel´nitskii, Mendeleev Commun.,
1995, 25.
7. L. I. Vereshchagin, L. G. Tikhonova, A. V. Maksikova, E. S.
Serebryakova, A. G. Proidakov, and T. M. Fimennova,
Zh. Org. Khim., 1980, 16, 730 [J. Org. Chem. USSR, 1980, 16
(Engl. Transl.)].
8. L. V. Batog, L. S. Konstantinova, V. Yu. Rozhkov, Yu. A.
Strelenko, O. V. Lebedev, and L. I. Khmel´nitskii, Khim.
Geterotsikl. Soedin., 2000, 100 [Chem. Heterocycl. Compd.,
2000, 36, 91 (Engl. Transl.)].
9. L. V. Batog, V. Yu. Rozhkov, Yu. A. Strelenko, O. V.
Lebedev, and L. I. Khmel´nitskii, Khim. Geterotsikl. Soedin.,
2000, 406 [Chem. Heterocycl. Compd., 2000, 36, 343 (Engl.
Transl.)].
Di[1ꢀ(4ꢀaminoꢀ1,2,5ꢀoxadiazolꢀ3ꢀyl)ꢀ4ꢀethoxycarbonylꢀ1Hꢀ
1,2,3ꢀtriazolꢀ4ꢀylmethyl] sulfide (18g). A mixture of compound
3a (1 g, 3.67 mmol), amide 17 (0.33 g, 4.4 mmol), and K2CO3
(0.26 g, 1.88 mmol) was refluxed in EtOH (30 mL) for 8 h.
10. L. V. Batog, V. Yu. Rozhkov, and M. I. Struchkova,
Mendeleev Commun., 2002, 159.

1934
Russ.Chem.Bull., Int.Ed., Vol. 54, No. 8, August, 2005
Rozhkov et al.
11. V. Yu. Rozhkov, L. V. Batog, E. K. Shevtsova, and M. I.
Struchkova, Mendeleev Commun., 2004, 76.
12. L. V. Batog, L. S. Konstantinova, and V. Yu. Rozhkov, Izv.
Akad. Nauk, Ser. Khim., 2005, 1859 [Russ. Chem. Bull., Int.
Ed., 2005, 54, 1915].
13. P. H. Olesen, A. R. Sorensen, B. Urso, P. Kurtzhals, A. N.
Bowler, U. Ehrbar, and B. F. Hansen, J. Med. Chem., 2003,
46, 3333.
14. WeygandꢀHilgetag, Organischꢀchemische Experimentierkunst,
Johann Ambrosius Barth Verlag, Leipzig, 1964, p. 942.
15. O. A. Rakitin, O. A. Zalesova, A. S. Kulikov, N. N. Makhova,
T. I. Godovikova, and L. I. Khmel´nitskii, Izv. Akad. Nauk,
Ser. Khim., 1993, 1949 [Russ. Chem. Bull., 1993, 42, 1865
(Engl. Transl.)].
18. M. A. Epishina, N. N. Makhova, L. V. Batog, L. S.
Konstantinova, and L. I. Khmel´nitskii, Mendeleev Commun.,
1994, 102.
19. L. V. Batog, V. Yu. Rozhkov, L. S. Konstantinova, V. Yu.
Eman, M. O. Dekaprilevich, Yu. T. Struchkov, S. E.
Semenov, O. V. Lebedev, and L. I. Khmel´nitskii, Izv. Akad.
Nauk, Ser. Khim., 1996, 1250 [Russ. Chem. Bull., 1996, 45,
1189 (Engl. Transl.)]; L. V. Batog, L. S. Konstantinova,
O. V. Lebedev, and L. I. Khmel´nitskii, Mendeleev Commun.,
1996, 193.
20. N. K. Kochetkov, Zh. Obshch. Khim., 1955, 25, 1366 [J. Gen.
Chem. USSR, 1955 (Engl. Transl.)].
21. A. B. Sheremetev, A. S. Kulikov, and L. I. Khmel´nitskii,
Izv. Akad. Nauk, Ser. Khim., 1993, 744 [Russ. Chem. Bull.,
1993, 42, 1189 (Engl. Transl.)].
16. O. Dimroth, Liebigs Ann. Chem., 1909, 364, 183.
17. A. B. Sheremetev and O. V. Kharitonova, Mendeleev
Commun., 1992, 157.
Received May 24, 2005