Electrophilic heterocyclization of 4,5-disubstituted 3-allylthio-4H-1,2,4- triazoles by the action of halogens

Article abstract of DOI:10.1007/s10593-011-0870-5

A study was carried out on the regioselectivity of the electrophilic heterocyclization of 4,5-disubstituted 3-allylthio-4H-1,2,4-triazoles by the action of bromine and iodine. Factors affecting the halogenation regioselectivity, namely, the nature of the

Full text of DOI:10.1007/s10593-011-0870-5

Chemistry of Heterocyclic Compounds, Vol. 47, No. 8, November, 2011 (Russian Original Vol. 47, No. 8, August, 2011)
ELECTROPHILIC HETEROCYCLIZATION
OF 4,5-DISUBSTITUTED 3-ALLYLTHIO-
4H-1,2,4-TRIAZOLES BY THE ACTION
OF HALOGENS
R. M. Usenko1, M. V. Slivka1*, and V. G. Lendel1
A study was carried out on the regioselectivity of the electrophilic heterocyclization of 4,5-disubstituted
3-allylthio-4H-1,2,4-triazoles by the action of bromine and iodine. Factors affecting the halogenation
regioselectivity, namely, the nature of the electrophilic reagent and the presence of lithium perchlorate,
were studied. A method was developed to obtain 5,6-dihydro-3H-[1,3]thiazolo[3,2-b]triazolium salts.
The structure of these salts was confirmed by spectral methods and chemical transformations.
Keywords: 3-allylthio-1,2,4-triazole, bromine, iodine, 5,6-dihydro-3H-[1,3]thiazolo[3,2-b]triazolium salts,
heterocyclization, regioselectivity.
Derivatives of [1,3]thiazolo[3,2-b][1,2,4]triazole display a broad spectrum of biological activity
including anticonvulsant [1], antimicrobial [2], and antituberculosis action [3]. These compounds are used as
pesticides in agriculture [4]. Functional thioderivatives of 1,2,4-triazole are used in analytical chemistry as
organic ligands in the photometric determination of heavy metals [5, 6].
The study of methods for the selective condensation of heterocyclic systems to the triazole ring opens
new prospects for the use of triazole derivatives. In the present work, we describe the reaction of halogens with
4,5-disubstituted 3-allylthio-1,2,4-triazoles 1 to obtain 5,6-dihydro-3H-[1,3]thiazolo[3,2-b]triazolium salts
(Scheme 1). Various researchers have described the electrophilic heterocyclization of 4-alkenyl-1,2,4-triazole-
3-thiones [7-10] and alkyl sulfides [11] to give 5,6-dihydro-3H-[1,3]thiazolo[3,2-c][1,2,4]triazole derivatives or
the corresponding sulfonium salts. The iodination of 4-unsubstituted 3-allyl-1,2,4-triazoles to give a mixture of
cyclization products has also been described [12].
Kim et al. [13, 14] have described the possibility of forming three isomeric structures (A, B, and C)
upon the cyclization of the allyl fragment at the heteroatom, which, most likely, is a consequence of the low
polarization of the double bond in the allyl fragment due to the weak (+I)-effect of the azolylthiol substituent
(Scheme 2). This finding, in turn, points to the high probability for different pathways for the halogenation of
the starting sulfide 1 to give structures A, B, and C through an electrophilic heterocyclization mechanism [15].
_______
*To whom correspondence should be addressed, e-mail: mvslivka@email.ua, depchem@univ.uzhgorod.ua.
1Uzhgorod National University, 53/1 O. Fedintsa St., Uzhgorod 88000, Ukraine.
__________________________________________________________________________________________
Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1248-1257, August, 2011.
Original article submitted March 28, 2011.
0009-3122/11/4708-1029©2011 Springer Science+Business Media, Inc.
1029

The reaction of sulfides 1 with a twofold excess of bromine and iodine was carried out in glacial acetic
acid at 15°C (Scheme 1). Thin-layer chromatography indicated that the precipitate formed is a mixture of two
1
products. H NMR spectral analysis of the bromination products of sulfides 1a-g indicates the formation of a
4:1 mixture of two isomers. The high regioselectivity of the cyclization permits the isolation of the predominant
isomer by fractional crystallization from 5:1 acetic acid–DMF. The minor product could not be isolated. The
spectral data show that the predominant product of the bromination of compounds 1a-g has structure A (salts 2a-g).
Scheme 1
CH2Br
–
Br3
+
N
N
R1
S
–
Br
CH2Br
N
R
+
N
N
N
N
Br2
Me2CO
2a–g
R1
R1
S
S
–
N
R
N
R
Br3
Br
+
N
N
2h–l
R1
S
1a–g
N
R
B
1,2a–f,h–k R = Ph, g,l R = Me; a,g,h,l R1 = Ph,
b,j R1 = 4-O2NC6H4, e R1 = 3-ClC6H4, f R1 = Bn,
O
O
c,i R1 =
N
O
CH2CH2
d,k R1 =
N
O
CH2CH2CH2
Scheme 2
b
CH2Hal
S
b
Hal
Hal2
– Hal–
+
+
a
a
..
N
N
a,c
c
N
..
S
S
A
b
c
Hal
+
N
..
+
N
CH2Hal
N
S
+
S
S
B
CH2Hal
C
1030

We should note that the nature of the substituent at C-5 of the triazole ring does not significantly affect
the regioselectivity of the bromination of thioether 1.
Treatment of yellow tribromides 2a-d,g with acetone at room temperature gives white
monobromides 2h-l, which have similar 1H NMR spectra (Table 1).
1
Analysis of the H NMR spectra of the crude product of the iodination of sulfide 1a also indicates
formation of a 3:1 mixture of two regioisomers (Scheme 3), from which salt 2m was isolated. In other words,
structure A is formed predominantly in iodination, while isomer C is the minor product. The >CH-I multiplet at
4.3 ppm characteristic for structure B is absent in the 1H NMR spectrum of the reaction mixture. We should note
that carrying out the iodination in the presence of an equivalent amount of lithium perchlorate (whose effect on
the regioselectivity of electrophilic addition to a double bond has been described by Vas'kevich et al. [16])
results in the formation of structure C as the predominant product and isomer A as the minor product, which
could not be isolated. Compound 3a was obtained as the perchlorate (Scheme 3). The change in the
regioselectivity of the cyclization in the iodination of sulfide 1a in the presence of lithium perchlorate is most
probably related to enhanced stability of the intermediate iodonium complex [12], which may rearrange to the
sulfonium cation with formation of structure C.
The action of potassium iodide in acetone or DMF on triiodides 2m,o leads to conversion to the
corresponding monoiodides 2p,r.
Evidence for the formation of the thiazolinotriazole cation is also found in the signals of the exocyclic
iodomethyl group carbon at 11.5 ppm (salts 2m and 3) in the 13C NMR spectrum of iodination products of
sulfide 1a.
Thus, we have shown that halogenation of 4,5-disubstituted 2-allylthio-1,2,4-triazoles 1 in acetic acid at
15°C regioselectively leads to the formation of thiazolinium salts 2. We have also shown that carrying out the
iodination of sulfide 1a in the presence of lithium perchlorate leads to structural isomer 3.
Scheme 3
–
–
CH2I
S
ClO4
ClO4
R
+
+
I2 + LiClO4
CH2I
N
N
N
N
R
–
S
+
+
N
N
Ph
Ph
A
1a–c
3
I3
–
–
+
N
I3
CH2I
S
CH2I
S
CH2I
I
N
+
N
+
N
2 I2
N
N
R
S
KI
N
R
R
N
N
Ph
Ph
2m–o
Ph
2p,r
C
O
2m,p, 3 R = Ph; 2n R = 4-O2NC6H4;
2o,r R =
N CH2CH2
O
We also investigated some chemical properties of salts 2a,h,m, specifically their reaction with O- or
N-nucleophiles. Opening of the thiazoline ring to give N-vinyl disulfide 4 occurs in the reaction of salts 2a,h,m
with nucleophiles and next treatment of the reaction mixture with water (Scheme 4).
1031

The attack of the nucleophile takes place at the nodal carbon atom, leading to an unstable pseudo base,
which converts to a sulfide upon opening of the thiazoline ring (in the case of N-nucleophiles through the
hydrolysis stage). Oxidation of the sulfide to a disulfide probably occurs by the action of atmospheric oxygen.
Opening of the thiazoline ring due to the action of the nucleophile as a base is accompanied by elimination of
hydrogen halide.
TABLE 1. 1H NMR Spectral Data for Compounds 2a-r and 3
Chemical shifts, δ, ppm (J, Hz)
Com-
pound
CH
R, R1
2
CH2
4
СН2Hаl
(1Н, m)
1
3
5
7.66-7.89 (10Н, m, H Ph)
5.44
4.88 (1Н, dd,
J = 3.3, J = 14.7);
5.15 (1Н, dd,
3.86-3.93 (1Н, m);
4.12 (1Н, two dd,
J = 2.1, J = 11.7)
2a
J = 3.3, J = 14.4)
7.51-7.72
(7Н, m, H Ph + C6H4NO2);
8.32 (2H, d,
5.41
5.37
5.31
5.41
5.37
5.40
5.44
5.37
5.41
5.31
4.92 (1Н, dd
J = 3.3, J = 14.4);
5.13 (1Н, dd,
3.85-3.91 (1Н, m);
4.07 (1Н, dd,
J = 2.1, J = 11.7)
2b
2c
2d
2e
2f
J = 9.3, C6H4NO2)
J = 3.3, J = 14.4)
3.11 (2H, m, CH2);
4.29 (2H, m, CH2);
7.74-8.50 (11H, m, H Ar)
4.62 (1Н, dd,
J = 3.0, J = 14.4);
4.96 (1Н, dd,
3.82 (1Н, m);
4.07 (1Н, m)
J = 3.0, J = 14.4)
2.10 (2H, m, CH2);
4.57 (1Н, dd,
3.82 (1Н, m);
4.03-4.24 (1Н, m)
2.79 (2H, t, J = 6.9, CH2);
4.05-4.24 (2H, m, CH2);
7.54-8.52 (11H, m, H Ar)
J = 3.0, J = 14.1);
4.89 (1Н, two dd,
J = 3.0, J = 14.1)
7.28-7.89 (9Н, m, H Ar)
4.88 (1Н, dd,
J = 3.3, J = 14.4);
5.11 (1Н, dd,
3.84-3.95 (1Н, m);
4.01-4.11 (1Н, m)
J = 3.3, J = 14.4)
4.14 (2H, s, CH2);
7.08-7.72 (10H, m, H Ph)
4.74 (1Н, dd,
J = 3.0, J = 14.1);
5.02 (1Н, dd,
3.71-3.84 (1Н, m);
3.96-4.27 (1Н, m)
J = 3.0, J = 14.1)
3.76 (3Н, s, СН3);
7.70-7.84 (5Н, m, H Ph)
4.77 (1Н, dd,
J = 3.0, J = 14.7);
5.01 (1Н, dd,
3.93 (1Н, dd,
J = 2.4, J = 11.7);
4.02 (1Н, dd,
2g
2h
2i
J = 3.0, J = 14.4)
J = 2.1, J = 11.7)
7.46-7.89 (10Н, m, Н Ar)
4.87 (1Н, dd,
J = 3.3, J = 14.4);
5.16 (1Н, dd,
3.88-4.24 (2Н, m)
J = 3.3, J = 14.4)
3.11 (2H, m, CH2);
4.29 (2H, m, CH2);
7.74-8.50 (11H, m, H Ar)
4.62 (1Н, dd,
J = 3.0, J = 14.4);
4.96 (1Н, dd,
3.82 (1Н, m);
4.07 (1Н, m)
J = 3.0, J = 14.4)
7.51-7.72
(5Н, 2Н, m, Ar, C6H4NO2);
8.32 (2H, d,
4.92 (1Н, dd,
J = 3.3, J = 14.4);
5.13 (1Н, dd,
3.85-3.91 (1Н, m);
4.07 (1Н, dd, J = 2.1,
J = 11.7)
2j
J = 9.3, C6H4NO2)
J = 3.3, J = 14.4)
2.10 (2H, m, CH2);
4.57 (1Н, dd,
3.82 (1Н, m);
2k
2.79 (2H, t, J = 6.9, CH2);
4.05-4.24 (2H, m,CH2);
7.54-8.52 (11H, m, H Ar)
J = 3.0, J = 14.1);
4.89 (1Н, dd,
J = 3.0, J = 14.1)
4.03-4.24 (1Н, m)
1032

TABLE 1 (continued)
1
2
3
4
5
3.75 (3Н, s, СН3);
7.70-7.84 (5Н, m, H Ph)
5.40
5.03
5.06
4.77 (1Н, dd,
J = 3.0, J = 14.4);
5.02 (1Н, dd,
3.93 (1Н, dd,
J = 2.1, J = 11.7);
5.02 (1Н, dd,
2l
J = 3.0, J = 14.4)
J = 2.1, J = 11.7)
7.41-7.71 (10Н, m, Н Ph)
4.80 (1Н, dd,
J = 3.6, J = 15.0);
5.13 (1Н, dd,
3.83-3.90 (1Н, m);
3.97 (1Н, dd,
J = 2.7, J = 13.2)
2m
2n
J = 3.6, J = 15.0)
7.69
4.88 (1Н, m);
5.15 (1Н, dd,
J = 3.3, J = 14.7)
3.79-3.98 (2Н, m)
(7Н, m, H Ph + C6H4NO2);
8.33 (2H, d,
J = 9.3, C6H4NO2)
3.13 (2H, m, CH2);
4.31 (2H, m, CH2);
7.76-8.48 (11H, m, H Ar)
4.63
5.02
4.63
4.90-5.12 (2Н, m) 3.85-3.91 (2Н, m)
2o
2p
2r
3
7.46 and 7.64
(10Н, two m, Н Ph)
4.78-4.82 (1Н, m); 3.92-3.98 (2Н, m)
5.11 (1Н, dd,
J = 3.2, J = 11.6)
3.13 (2Н, m, СН2);
4.31 (2Н, m, СН2);
7.76-8.48 (11H, m, H Ar)
4.94-5.08 (2Н, m) 3.83-3.91 (2Н, m)
7.41-7.68 (10Н, m, H Ph)
3.92 and 4.97
4.33-4.41 (2Н, m) 3.92-3.98 (2Н, m)
(1Н, 2m)
Scheme 4
CH2Hal
S
+
N N
–NR2
N N
+
N
N
N
Ph
S
Ph
NR2
Ph
S
N
– HHal
N
NR2
Ph
Ph
–NR2
Ph
a
H2O
(– HNR2)
2a,h,m
b
CH2Hal
SH
–OH
S
+
N N
N N
N N
[O]
N
N
Ph
S
Ph
Ph
S
N
O
– HHal
Ph
N
OH
O
N
N
Ph
Ph
–OH
Ph
Ph
2
4
a - morpholine, (CH2)4NH, or (CH2)5NH
b - NaOH/H2O, Na2CO3/H2O or AcONa/H2O
The formation of elimination product 4 in all cases in the nucleophilic ring opening (singlets for the
methylene protons at 4.24 ppm, trans methylidene proton at 5.59 ppm, and cis methylidene proton at 6.02 ppm
1033

were found in the 1H NMR spectrum) also supports our proposed structure for salts 2 as the major product of the
haloheterocyclization of allyl sulfides 1.
Thus, we have demonstrated the feasibility and studied the factors affecting the regioselectivity of the
halogenation of 3-allylthio-4H-1,2,4-triazoles. A method was developed for the preparation of 5,6-dihydro-
3H-[1,3]thiazolo[3,2-b][1,2,4]triazolium salts, which may be used for the preparation of vinyl derivatives of
symmetrical triazoles.
EXPERIMENTAL
1
The IR spectra were obtained on a Pye-Unicam SP 3-300 spectrometer for KBr pellets. The H NMR
spectra were obtained on a Varian VXR-300 spectrometer at 300 MHz for compounds 2a-l,n,o,r, and 4 and a
Varian Mercury-400 spectrometer at 400 MHz for compounds 2m,p and 3. The 13C NMR spectra were taken on
a Varian Mercury-400 spectrometer at 100 MHz in DMSO-d6 with TMS as internal standard. The melting
points were determined on a Kofler hot stage. The thin-layer chromatographic analysis was carried out on
Sorbfil silica gel plates with eluents: 1:3:1 ethanol–ether–hexane for compounds 2b-f,i-k,n,o,r, 1:3:2 acetic
acid–ethanol–hexane for compounds 2a,g,h,l,m,p and 3a, and 5:1 2-propanol–water for 4a. Iodine vapor was
used for development.
The method for the synthesis of sulfides 1 was described in our previous work [17, 18].
Bromination of Sulfides 1a-g (General Method). 3-S-Allylthiotriazoles 1a-g (0.005 mol) were
dissolved in glacial acetic acid, chloroform, or tetrachloromethane (20 ml). Then, a solution of bromine
(0.53 ml, 0.01 mol) in 10 ml glacial acetic acid, chloroform, or tetrachloromethane was added slowly dropwise
to the solution obtained with cooling and constant stirring. The reaction mixture was stirred for 4 h. The
precipitate formed was filtered off and washed with glacial acetic acid and diethyl ether. The major product 2a-g
was isolated by recrystallization from 5:1 acetic acid–DMF.
6-Bromomethyl-2,3-diphenyl-5,6-dihydro-3H-[1,3]thiazolo[3,2-b][1,2,4]triazol-7-ium Tribromide
(2a) was obtained in 63% yield as yellow crystals; mp 159-160°C, Rf 0.94. Found, %: Br 52.11; N 6.97; S 5.19.
C17H15Br4N3S. Calculated, %: Br 52.14; N 6.85; S 5.23.
6-Bromomethyl-2-(4-nitrophenyl)-3-phenyl-5,6-dihydro-3H-[1,3]thiazolo[3,2-b][1,2,4]triazol-7-ium
Tribromide (2b) was obtained in 61% yield as yellow crystals; mp 165-167°C, Rf 0.23. Found, %: Br 48.49;
N 8.57; S 4.95. C17H14Br4N4O2S. Calculated, %: Br 48.57; N 8.51; S 4.87.
6-Bromomethyl-2-[2-(1,3-dioxo-1H-benzo[de]isoquinolin-2(3H)-yl)ethyl]-3-phenyl-5,6-dihydro-
3H-[1,3]thiazolo[3,2-b][1,2,4]triazol-7-ium Tribromide (2c) was obtained in 51% yield as yellow crystals;
mp 195-196°C, Rf 0.25. Found, %: Br 42.02; N 7.47; S 4.29. C25H20Br4N4O2S. Calculated, %: Br 42.05; N 7.37;
S 4.22.
6-Bromomethyl-2-[3-(1,3-dioxo-1H-benzo[de]isoquinolin-2(3H)-yl)propyl]-3-phenyl-5,6-dihydro-
3H-[1,3]thiazolo[3,2-b][1,2,4]triazol-7-ium Tribromide (2d) was obtained in 70% yield as yellow crystals;
mp 243-244°C, Rf 0.28. Found, %: Br 41.21; N 7.31; S 4.09. C26H22Br4N4O2S. Calculated, %: Br 41.29; N 7.24;
S 4.14.
6-Bromomethyl-2-(3-chlorophenyl)-3-phenyl-5,6-dihydro-3H-[1,3]thiazolo[3,2-b][1,2,4]triazol-7-ium
Tribromide (2e) was obtained in 62% yield as yellow crystals; mp 125-127°C, Rf 0.31. Found, %: N 6.31;
S 5.09. C17H14Br4ClN3S. Calculated, %: N 6.49; S 4.95.
2-Benzyl-6-bromomethyl-3-phenyl-5,6-dihydro-3H-[1,3]thiazolo[3,2-b][1,2,4]triazol-7-ium Tribromide
(2f) was obtained in 58% yield as yellow crystals; mp 205-206°C, Rf 0.35 . Found, %: Br 50.81; N 6.58; S 5.09.
C18H17Br4N3S. Calculated, %: Br 50.97; N 6.70; S 5.11.
6-Bromomethyl-3-methyl-2-phenyl-5,6-dihydro-3H-[1,3]thiazolo[3,2-b][1,2,4]triazol-7-ium Tri-
bromide (2g) was obtained in 80% yield as yellow crystals; mp 185°C, Rf 0.67. Found, %: Br 58.11; N 7.58;
S 5.69. C12H13Br4N3S. Calculated, %: Br 58.01; N 7.63; S 5.82.
1034

Preparation of Monobromides 2h-l. (General Method). Tribromides 2a-d,g (0.005 mol) were stirred
in acetone (50 ml) for 1 h. The final product was filtered off, washed with diethyl ether, and crystallized from
5:1 acetic acid–DMF.
6-Bromomethyl-2,3-diphenyl-5,6-dihydro-3H-[1,3]thiazolo[3,2-b][1,2,4]triazol-7-ium Bromide (2h)
was obtained in 84% yield as white crystals; mp 195°C, Rf 0.67. Found, %: Br 35.11; N 9.36; S 7.19.
C17H15Br2N3S. Calculated, %: Br 35.26; N 9.27; S 7.07.
6-Bromomethyl-2-[2-(1,3-dioxo-1H-benzo[de]isoquinolin-(3H)-yl)ethyl]-3-phenyl-5,6-dihydro-
3H-[1,3]thiazolo[3,2-b][1,2,4]triazol-7-ium Bromide (2i) was obtained in 67% yield as white crystals; mp
a
282-284°C, Rf 0.39. Found, %: Br 26.51; N 9.37; S 5.29. C25H20Br2N4O2S. Calculated, %: Br 26.62; N 9.33;
S 5.34.
6-Bromomethyl-2-(4-nitrophenyl)-3-phenyl-5,6-dihydro-3H-[1,3]thiazolo[3,2-b][1,2,4]triazol-7-ium
Bromide (2j) was obtained in 91% yield as white crystals; mp 190-191°C, Rf 0.89. Found, %: Br 32.11;
N 11.37; S, 6.39. C17H14Br2N4O2S. Calculated, %: Br 32.08; N 11.25; S 6.44.
6-Bromomethyl-2-[3-(1,3-dioxo-1H-benzo[de]isoquinolin-2(3H)-yl)propyl]-3-phenyl-5,6-dihydro-
3H-[1,3]thiazolo[3,2-b][1,2,4]triazol-7-ium bromide (2k) was obtained in 98% yield as white crystals;
mp 265-266°C, Rf 0.89. Found, %: Br 25.98; N 9.19; S 5.14. C26H22Br2N4O2S. Calculated, %: Br 26.01; N 9.12;
S 5.22.
6-Bromomethyl-3-methyl-2-phenyl-5,6-dihydro-3H-[1,3]thiazolo[3,2-b][1,2,4]triazol-7-ium Bromide
(2l) was obtained in 98% yield as white crystals; mp 195-196°C, Rf 0.83. Found, %: Br 40.68; N 10.91; S 8.34.
C12H13Br2N3S. Calculated, %: Br 40.86; N 10.74; S 8.20.
Preparation of Triiodides 2m-o (General Method). A solution of iodine (2.54 g, 10 mmol) in
ethanol (100 ml) was added in 3-5 ml portions to sulfides 1a-c (5 mmol) in ethanol (50 ml). The reaction
mixture was stirred for seven days. The desired product 2m-o was filtered off, washed on the filter with ether
(35 ml), and crystallized from acetic acid.
6-Iodomethyl-2,3-diphenyl-5,6-dihydro-3H-[1,3]thiazolo[3,2-b][1,2,4]triazol-7-ium
Triiodide
13
(2m) was obtained in 62% yield; mp 154-156°C, Rf 0.71. C NMR spectrum, , ppm (J, Hz): 11.5; 35.8; 56.8;
123.1; 128.1; 129.5; 129.9; 130.2; 131.5; 131.7; 132.9; 152.1; 152.8. Found, %: I 63.28; N 5.31; S 4.04.
C17H15I4N3S. Calculated, %: I 63.37; N 5.25; S 4.00.
6-Iodomethyl-2-(4-nitrophenyl)-3-phenyl-5,6-dihydro-3H-[1,3]thiazolo[3,2-b][1,2,4]triazol-7-ium
Triiodide (2n) was obtained in 53% yield; mp 171-173°C, Rf 0.14. Found, %: I 60.08; N 6.71; S 3.64.
C17H14I4N4O2S. Calculated, %: I 60.00; N 6.62; S 3.79.
2-[2-(1,3-Dioxo-1H-benzo[de]isoquinolin-2(3H)-yl)ethyl]-6-iodomethyl-3-phenyl-5,6-dihydro-
3H-[1,3]thiazolo[3,2-b][1,2,4]triazol-7-ium Triiodide (2o) was obtained in 56% yield; mp 116-118°C, Rf 0.16.
Found, %: I 53.64; N 5.97; S 3.20. C25H20I4N4O2S. Calculated, %: I 53.54; N 5.91; S 3.38.
Preparation of Monoiodides 2p,r (General Method). Triiodides 2m,o (1.6 mmol) were dissolved in a
minimal amount of DMF and potassium iodide (0.27 g, 1.6 mmol) was added with stirring. The precipitate was
filtered off and crystallized from 3:2 acetic acid–DMF.
6-Iodomethyl-2,3-diphenyl-5,6-dihydro-3H-[1,3]thiazolo[3,2-b][1,2,4]triazol-7-ium Iodide (2p) was
obtained in 92% yield; mp 185-186°C, Rf 0.64. Found, %: I 46.28; N 7.77; S 5.94. C17H15I2N3S. Calculated, %:
I 46.38; N 7.68; S 5.86.
2-[2-(1,3-Dioxo-1H-benzo[de]isoquinolin-2(3H)-yl)ethyl]-6-iodomethyl-3-phenyl-5,6-dihydro-
3H-[1,3]thiazolo[3,2-b][1,2,4]triazol-7-ium Iodide (2r) was obtained in 78% yield; mp 193-194°C, Rf 0.69.
Found, %: I 36.48; N 7.97; S 4.59. C25H20I2N4O2S. Calculated, %: I 36.55; N 8.07; S 4.62.
5-Iodomethyl-2,3-diphenyl-5,6-dihydro-3H-[1,3]thiazolo[3,2-b][1,2,4]triazol-7-ium Perchlorate (3a).
Lithium perchlorate (0.64 g, 6 mmol) was added to sulfide 1a (1.76 g, 6 mmol) in glacial acetic acid (50 ml) and
heated until the solution was fully homogeneous. A solution of iodine (1.52 g, 6 mmol) in glacial acetic acid
(100 ml) was added to the cooled solution. The reaction mixture was stirred for 48 h. The desired product 3a
was filtered off, washed on the filter with ether (35 ml), and crystallized from acetic acid to give perchlorate 3a
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in 53% yield; mp 217-219°C, Rf 0.72. 13C NMR spectrum, , ppm: 11.5; 49.4; 68.7; 123.8; 126.7; 128.0; 129.5;
130.0; 131.5; 132.5; 133.0; 157.5; 159.8. Found, %: N 7.91; S 6.04. C17H15ClIN3O4S. Calculated, %: N 8.08;
S 6.17.
2,2'-(Diprop-1-ene-3,2-diyldithio)bis(4,5-diphenyl-2,4-dihydro-3H-1,2,4-triazol-3-one) (4). A. Salts
2a,h,m (1 mmol) were stirred in 5 ml amine (morpholine, piperidine, or pyrrolidine) at room temperature for
2 h. The reaction mixture was poured into 100 ml water. The final product, which settled as a precipitate, was
crystallized from acetone to give compound 4 in 76% yield (upon morphine action) as white crystals;
mp 106-108°C, Rf 0.87.
B. Salt 2a (0.61 g, 1 mmol) was dissolved in a minimal amount of DMSO or DMF and Na2CO3 (or
NaOH or 10% aqueous sodium acetate) (5 mmol) was added to the solution obtained. The mixture was stirred
for 4 h. Crystallization of the final product from acetone gave compound 4 in 85% yield (upon Na2CO3 action)
as white crystals; mp 107-109°C, Rf 0.87.
1
IR spectrum, , cm-1: 505 w (S–S), 1700 m (C=O). H NMR spectrum, , ppm (J, Hz): 4.24 (2H, s,
CH2); 5.59 (1H, s, =CH2); 6.02 (1H, s, =CH2); 7.37 (5H, m); 7.44 (2H, m); and 7.58 (3H, m, H Ph). Found, %:
N 13.55; S 10.33. C34H28N6O2S2. Calculated, %: N 13.63; S 10.40.
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