Gas-phase pyrolysis of 4-amino-3-allylthio-1,2,4-triazoles: A new route to [1,3]thiazolo[3,2-b][1,2,4]triazoles

Article abstract of DOI:10.1039/b007638o

A short route to the [1,3]thiazolol[3,2-b]-[1,2,4]triazole ring system in moderate overall yield was provided by an unusual pyrolysis sequence. The carbon atoms in the fused triazole and thaizole rings were derived from a 4-aminotriazole-3-thione unit and allyl groups. Dry-flash chromatography was carried out on silica gel using a hexane-ethyl acetate gradient as eluent.

Full text of DOI:10.1039/b007638o

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Gas-phase pyrolysis of 4-amino-3-allylthio-1,2,4-triazoles:
a new route to [1,3]thiazolo[3,2-b][1,2,4]triazoles
Dale D. J. Cartwright,a Bernard A. J. Clarkb and Hamish McNab*a
1
a Department of Chemistry, The University of Edinburgh, West Mains Road, Edinburgh,
UK EH9 3JJ
b Kodak European Research and Development, Headstone Drive, Harrow, Middlesex,
UK HA1 4TY
Received (in Cambridge, UK) 20th September 2000, Accepted 13th December 2000
First published as an Advance Article on the web 19th January 2001
Flash vacuum pyrolysis of the 3-allylthio derivatives of 4-amino-4H-1,2,4-triazoles 10–13 and 15–17 at 750–850 ЊC
(10Ϫ2–10Ϫ3 Torr) gives [1,3]thiazolo[3,2-b][1,2,4]triazoles 19 and 24–29 in ca. 50% yield. The mechanism is thought to
involve initial [3,3]sigmatropic shift of the allyl group, followed by cleavage of the N–N bond to generate a thiaza-
allyl radical, which then undergoes cyclisation, rearrangement and alkyl group extrusion.
In previous work we have used the flash vacuum pyrolysis
(FVP) reactions of aromatic allylthio compounds to generate
thiophenoxyl radicals which can take part in rearrangement
and cyclisation reactions.1–3 In attempting to extend this
methodology into the heterocyclic series we have discovered in
one case an unusual sequence involving a [3,3]sigmatropic shift,
thiaza-allyl radical generation, cyclisation, rearrangement and
alkyl group extrusion, all of which leads to a convenient
synthesis of the [1,3]thiazolo[3,2-b][1,2,4]triazole ring system4
1 in two steps from readily available N-amino-1,2,4-triazoles 2
(Scheme 1).
ing anhydrous potassium carbonate gave products which were
obtained as single isomers in 54–81% yield. The product
obtained from the 5-unsubstituted compound 3 decomposed
on work-up under these conditions, but a product was obtained
in satisfactory yield (79%) when the reaction was carried out
using acetonitrile as the solvent. The assignment of the prod-
ucts as the S-allyl compounds 10–12, 15 and 16 followed in
particular from their 13C NMR spectra. Thus N-alkylation
(either at the exocyclic amino group or at the ring N2 atom)
would give a product which has a thione group. These are
known to show signals in the range δC 166–167 in triazole-3-
thiones,8 whereas the spectra of 10–12, 15 and 16 show no
peaks at δC >155 ppm. The corresponding reaction of 4 with
either crotyl chloride 8 or 3-chlorobut-1-ene 9 gave a mixture
of S-allylated isomers in 6:1 and 13:1 ratio respectively. The
13C NMR DEPT spectrum of the mixture confirmed that both
isomers had a CH2 group adjacent to the sulfur atom (δC 35.65)
and therefore they are likely to be the E and Z isomers of 13.
Recrystallisation from toluene gave a single compound which is
likely to be the E-isomer. No trace of the regioisomer 14 was
apparent from the crude spectra. Similarly the butenyl com-
pound 17 was obtained by reaction of the phenyl-substituted
precursor 5 with crotyl chloride.‡
Scheme 1
FVP of the S-allyl compound 11 at 650 ЊC (0.01 Torr) gave a
mixture of two products in 9:1 ratio from which the major
compound could be isolated by chromatography on silica. This
product was clearly isomeric with the starting material and was
identified as the N-allyl compound 18 by its spectra (Scheme 3).
Scheme 3 Reagents and conditions: (i) 650 ЊC (0.01 Torr).
Scheme 2
For example, the thione function is apparent from the signal at
δC 165.99 in the 13C NMR spectrum (see above). [3,3]Sigma-
tropic rearrangements of this type have been previously
reported in the triazole series8 and in the present example may
take place to some extent during the sublimation stage of the
pyrolysis.
The triazole precursors 3–5 (Scheme 2) were readily obtained
by literature methods as described briefly in the Experimental
section.5–7 Allylation of the triazoles 4 and 5 using allyl bromide
6 or methallyl chloride 7† in N,N-dimethylformamide contain-
† The IUPAC name for methallyl is 2-methylprop-2-enyl.
‡ The IUPAC name for crotyl is but-2-enyl.
DOI: 10.1039/b007638o
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Scheme 4
At higher furnace temperatures, FVP of 11 gave a single
radicals are more reactive than aminyl radicals in such competi-
major product (identical with the minor product obtained in
the 650 ЊC pyrolysis described above) which was purified by
distillation. The mass spectrum of this material showed a
molecular ion at m/z 139 corresponding to loss of 31 Daltons
(= CH5N) from the starting material. The assignment of the
structure of the product as the known9 2-methyl[1,3]thiazolo-
[3,2-b][1,2,4]triazole 19 (54%) followed by comparison of its
tive cyclisation situations. Alternatively, the 5-exo-trig mode of
cyclisation (to give 21) may be inherently favoured over the
5-endo-trig to give 23. Second, no trace of the dimethylthiazolo-
[3,2-b][1,2,4]triazole 24 (see below) which might have been
formed by loss of a hydrogen atom from 22, was observed in
the crude pyrolysate; C–C cleavage is normally observed
in preference to C–H cleavage under competitive conditions in
the gas-phase.10
The synthetic potential of this two step sequence from
4-amino-1,2,4-triazole-3-thiones to [1,3]thiazolo[3,2-b][1,2,4]-
triazoles was then investigated using the 5-unsubstituted com-
pound 10, the 5-methyltriazoles 12 and 13, and the 5-phenyl
compounds 15–17 as model substrates. In all cases the pyrolysis
step was carried out in the range 750–850 ЊC (10Ϫ2–10Ϫ3 Torr)
and the products were purified by Kugelrohr distillation; in
general, chromatography was not required. Pyrolysis of 10
(850 ЊC) gave the unsubstituted [1,3]thiazolo[3,2-b][1,2,4]-
triazole 25 (45%) and that of the methallyl derivative 12 gave
the expected 2,5-dimethyl[1,3]thiazolo[3,2-b][1,2,4]triazole 24
in 48% yield. In the case of the butenyl precursor 13, the initial
sigmatropic shift produces 30 and hence leads to the 2,6-
1
spectra with those in the literature. For example the H NMR
spectrum shows three signals in 1:1:3 ratio [δH 7.69 (J 4.5 Hz),
6.91 (J 4.5 Hz) and 2.50] which correspond closely with the
reported data for 19 [δH 7.69 (J 5 Hz), 6.91 (J 5 Hz) and
2.47].9 In addition the mass spectrum of our product (see
Experimental section) shows the same initial breakdown peaks
as previously reported.9
A possible mechanism for this unexpected transformation is
shown in Scheme 4. After the initial [3,3]sigmatropic shift to
give 18, cleavage of the N–N bond apparently takes place to
generate the resonance-stabilised radical 20. This species then
adds exclusively from its sulfur centre 20c in 5-exo-trig fashion
to the double bond of the allyl group. The primary radical 21
thus generated can achieve more stability by hydrogen shift
from the site adjacent to the bridgehead nitrogen atom to give
22. Aromatisation by C–C cleavage (and ejection of a methyl
radical) gives the product 19. Two instances of high selectivity
in the chemistry of these radicals are apparent in this sequence.
First, no products were obtained from an alternative cyclisation
route which formally involves the nitrogen-centred canonical
form 20b (to give the secondary radical intermediate 23). This
suggests either that formation of 23 is reversible or that thiyl
dimethyl[1,3]thiazolo[3,2-b][1,2,4]triazole skeleton 26 (54%).
Pyrolysis of the phenyl-substituted triazoles 15–17 proceeded
normally and the [1,3]thiazolo[3,2-b][1,2,4]triazoles 27–29
were obtained in 23, 48 and 54% yields respectively, though
chromatography was required to purify 29. In general, the
J. Chem. Soc., Perkin Trans. 1, 2001, 424–428
425

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2,6-disubstituted products were obtained in a less pure state
than the other derivatives. 2,5-Disubstitution in the
[1,3]thiazolo[3,2-b][1,2,4]triazole ring system is apparently a
rare substituent pattern4 and both 24 and 28 are new
compounds.
obtained as white crystals (6.31 g, 97%) mp 203–204 ЊC (lit.,6
205–206 ЊC); δH ([2H]6DMSO) 13.40 (1H, s), 5.50 (2H, s) and
2.22 (3H, s).
4-Amino-5-phenyl-2,4-dihydro-3H-1,2,4-triazole-3-thione 5
In the pyrolyses of the phenyl-substituted substrates 15–17,
some benzonitrile was detected in the crude pyrolysate, presum-
ably due to breakdown of the heterocycle at the high temper-
atures required for the initial N–N bond cleavage. Since
pyrolysis of 16 or 17 at 750 ЊC (rather than 850 ЊC) did not
significantly reduce the level of benzonitrile, an attempt was
made to design a substrate in which the co-formed aminyl
radical was stabilised. Thus condensation of 4 with 2,5-
dimethoxytetrahydrofuran gave the pyrrolyltriazole 31 (87%),
which on FVP at 750 ЊC (10Ϫ2 Torr) gave a mixture of the
[1,3]thiazolo[3,2-b][1,2,4]triazole 19 (15%) and pyrrole, which
were separated by chromatography. Since the yield of product
was much lower than that obtained from the pyrolysis of 11 and
a chromatographic separation was required, this strategy was
not pursued further.
Finally, in an attempt to induce cyclisation without an initial
sigmatropic shift, the benzyl compounds 32 and 33 were syn-
thesised by standard methods and subjected to FVP, but no
cyclisation products were obtained (see Experimental section).
Although many spectroscopic studies of the [1,3]thiazolo-
[3,2-b][1,2,4]triazole system have been carried out, no system-
atic study of their 13C NMR spectra has been reported.4 The
parent compound of the system 25 apparently shows only three
signals in the proton decoupled spectrum, at δC 156.34, 119.86
and 113.85. However, a 1H coupled spectrum revealed the
bridgehead quaternary signal (C-3a), also at δC 156.34, and the
following coupling constants: C-2, 1JCH 208.7; C-5, 1JCH 195.2,
2JCH 10.2; C-6 1JCH 198.2, 2JCH 7.2 Hz. The 2-methyl compound
19 shows 4 signals due to the ring carbon atoms, quaternaries at
δC 166.52 (C-2) and 156.84 (C-3a) and methine resonances
at δC 119.66 and 112.14. Because methyl substitution at an
adjacent position is likely to cause a high frequency shift of that
signal (cf. data for thiazoles11,12) comparison of the spectra of
19, 24 and 26 allow the assignment of the resonances of C5
(δC 112–114) and C6 (δC 119–120) in compounds 19 and 24.
Further assignments are given in the Experimental section.
In conclusion we have shown that an unusual pyrolysis
sequence has provided a short route to the [1,3]thiazolo[3,2-b]-
[1,2,4]triazole ring system in moderate overall yield. The
carbon atoms in the fused triazole and thiazole rings are
derived initially from a 4-aminotriazole-3-thione unit and an
allyl group respectively. The sequence is compatible with sub-
stituents at all three possible positions on the rings and com-
plements traditional condensation routes from triazoles to the
[1,3]thiazolo[3,2-b][1,2,4]triazole system.4
This compound was made by treatment of benzoic acid
hydrazide (1.0 g, 7.4 mmol) with carbon disulfide (0.84 g, 0.011
mol) under basic conditions in ethanol followed by reaction
with aqueous hydrazine hydrate (0.38 g, 0.012 mol).7 The
triazole 5 so obtained (0.49 g, 35%) had mp 204–206 ЊC (lit.,6
204–206 ЊC); δH ([2H]6DMSO) 7.60 (5H, m) and 5.83 (2H, s);
m/z 192 (Mϩ, 100%) and 104 (45).
Allylation of 4-amino-3H-1,2,4-triazole-3-thione derivatives
The appropriate 1,2,4-triazole 3–5 (8 mmol) was added to
N,N-dimethylformamide (50 cm3) containing potassium
carbonate (1.0 g, 8 mmol). The appropriate allyl halide 6–9
(8 mmol) was added dropwise with stirring, then the mixture
was stirred at room temperature for 21–48 hours. The inorganic
salts were removed by filtration, the filtrate was concentrated
in vacuo, dichloromethane (20 cm3) was added and the mixture
was filtered once more. The product was obtained on removal
of the solvent. The following preparations were carried out by
this method:
4-Amino-5-methyl-2,4-dihydro-3H-1,2,4-triazole-3-thione 4
(1.04 g, 8 mmol) and allyl bromide 6 (0.96 g, 8 mmol) gave, after
48 h, 4-amino-3-allylthio-5-methyl-4H-1,2,4-triazole 11 as a pale
pink solid (1.1 g, 81%), mp 77–80 ЊC (from toluene) [Found,
MHϩ (FAB) 171.0710. C6H11N4S requires MH 171.0704];
δH 5.91 (1H, m), 5.15 (2H, m), 4.83 (2H, s), 3.68 (2H, m) and
2.37 (3H, s); δC 153.48 (quat), 150.31 (quat), 132.62 (CH),
118.80 (CH2), 36.04 (CH2) and 10.23 (CH3); m/z (FAB) 171
(MHϩ, 100%).
4-Amino-5-methyl-2,4-dihydro-3H-1,2,4-triazole-3-thione 4
(1.04 g, 8 mmol) and 2-methylprop-2-enyl chloride 7 (0.72 g,
8 mmol) gave, after 21 h, 4-amino-3-(2-methylprop-2-enyl)thio-
5-methyl-4H-1,2,4-triazole 12 as a white solid, (0.6 g, 81%),
mp 102–103 ЊC (from toluene) (Found, Mϩ 184.0782. C7H12N4S
requires M 184.0783); δH 4.86 (1H, m), 4.82 (1H, m), 4.64 (2H,
s), 3.71 (2H, s), 2.39 (3H, s) and 1.86 (3H, m); δC 153.42 (quat),
150.62 (quat), 140.36 (quat), 115.03 (CH2), 40.77 (CH2), 20.99
(CH3) and 10.24 (CH3); m/z 184 (Mϩ, 55%), 169 (68), 130 (31),
102 (66) and 70 (100).
4-Amino-5-methyl-2,4-dihydro-3H-1,2,4-triazole-3-thione 4
(1.04 g, 8 mmol) and but-2-enyl chloride 8 (0.72 g, 8 mmol)
gave, after 21 h, a 6:1 mixture of E and Z isomers, from which
4-amino-3-(but-2-enylthio)-5-methyl-4H-1,2,4-triazole 13 was
obtained as a white solid after recrystallisation from toluene,
(0.26 g, 50%) mp 105–107 ЊC (from toluene) (Found, C, 43.6;
H, 6.3; N, 28.75. C7H12N4Sؒ0.5H2O requires C, 43.5; H, 6.2; N,
29.0%. Found, Mϩ,184.0790. C7H12N4S requires M 184.0783);
δH 5.55 (1H, m), 5.50 (1H, m), 4.82 (2H, s), 3.60 (2H, m), 2.33
(3H, s) and 1.58 (3H, d, J 4.8); δC 153.28 (quat), 150.57 (quat),
130.50 (CH), 125.13 (CH), 35.65 (CH2), 17.56 (CH3) and 10.15
(CH3); m/z 184 (Mϩ, 19%), 169 (74), 143 (49), 130 (71) and 55
(100).
Experimental
Unless otherwise stated 1H and 13C NMR spectra were
recorded in [2H]chloroform at 250 (or 200) and 63 (or 50) MHz
respectively and mass spectra were recorded under electron
impact (EI) conditions. Coupling constants are quoted in Hz.
Dry-flash chromatography was carried out on silica gel (GF254
using a hexane–ethyl acetate gradient as eluent.
)
The corresponding reaction of 4-amino-5-methyl-2,4-di-
hydro-3H-1,2,4-triazole-3-thione 4 (1.04 g, 8 mmol) and
3-chlorobut-1-ene 9 (0.72 g, 8 mmol) gave, after 21 h, a 13:1
mixture of the E and Z isomers of 13, whose spectra were
identical with those reported above.
4-Amino-5-phenyl-2,4-dihydro-3H-1,2,4-triazole-3-thione 5
(1.54 g, 8 mmol) and allyl bromide 6 (0.96 g, 8 mmol) gave,
after 48 h, 4-amino-3-allylthio-5-phenyl-4H-1,2,4-triazole 15 as
a white solid, (0.74 g, 64%), mp 132–134 ЊC (from toluene)
(Found, C, 55.75; H, 5.2; N, 23.3. C11H12N4Sؒ0.25H2O requires
C, 55.8; H, 5.3; N, 23.7%); δH 8.00 (2H, m), 7.44 (3H, m), 5.99
(1H, m), 5.19 (2H, m), 4.82 (2H, s) and 3.81 (2H, m); δC 154.04
(quat), 152.06 (quat), 132.61 (CH) 129.93 (CH), 128.44
4-Amino-2,4-dihydro-3H-1,2,4-triazole-3-thione 3
Treatment of thiocarbohydrazide (5.3 g, 0.05 mol) with
refluxing formic acid (10 cm3)5 gave the parent triazole 3 (3.2 g,
55%) mp 166–167 ЊC (lit.,5 166–167 ЊC); δH ([2H]6DMSO) 13.51
(1H, s), 8.41 (1H, s) and 5.62 (2H, s).
4-Amino-5-methyl-2,4-dihydro-3H-1,2,4-triazole-3-thione 4
Prepared from thiocarbohydrazide (5.3 g, 0.05 mol) and acetic
acid (15 cm3) by the standard method6 the product 4 was
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(CH), 127.99 (CH), 126.32 (quat), 119.12 (CH2) and 36.10
(CH2); m/z 232 (Mϩ, 39%), 217 (36), 129 (47), 103 (80) and 41
(100).
54%), bp 120 ЊC (2.5 Torr) (mp lit.,9 49.5–51 ЊC); δH 7.69 (1H, d,
3
3J 4.5), 6.91 (1H, d, J 4.5) and 2.50 (3H, s); δC 166.52 (quat),
156.84 (quat), 119.66 (CH), 112.14 (CH) and 14.79 (CH3);
4-Amino-5-phenyl-2,4-dihydro-3H-1,2,4-triazole-3-thione 5
(1.54 g, 8 mmol) and 2-methylprop-2-enyl chloride 7 (0.72 g, 8
mmol) gave, after 48 h, 4-amino-3-(2-methylprop-2-enyl)thio-5-
phenyl-4H-1,2,4-triazole 16 as a white solid, (0.66 g, 54%), mp
130–132 ЊC (from toluene) (Found, C, 58.3; H, 5.85; N, 22.5.
C12H14N4S requires C, 58.5; H, 5.7; N, 22.8%); δH 8.00 (2H, m),
7.40 (3H, m), 4.92 (2H, m), 4.84 (2H, m), 3.78 (2H, s) and 1.87
(3H, s); δC 153.97 (quat), 152.44 (quat), 140.23 (quat), 129.94
(CH), 128.41 (CH), 128.00 (CH), 126.23 (quat), 115.23 (CH2),
40.62 (CH2) and 21.03 (CH3); m/z 246 (Mϩ, 88%), 201 (52), 143
(30), 103 (56) and 70 (100).
4-Amino-5-phenyl-2,4-dihydro-3H-1,2,4-triazole-3-thione 5
(1.54 g, 8 mmol) and but-2-enyl chloride 8 (0.72 g, 8 mmol)
gave, after 48 h, 4-amino-3-(but-2-enylthio)-5-phenyl-4H-1,2,4-
triazole 17 as a gummy yellow solid, which was recrystallised
from toluene to give the product as pale yellow crystals (0.64 g,
33%), mp 145–147 ЊC (from toluene) [Found, MHϩ (FAB)
247.1016. C12H15N4S requires MHϩ 247.1017]; δH 7.99 (2H, m),
7.44 (3H, m), 5.66 (1H, m), 5.63 (1H, m), 4.78 (2H, s), 3.76 (2H,
m) and 1.65 (3H, d, J 4.8); δC 153.94 (quat), 152.29 (quat),
130.89 (CH), 129.91 (CH), 128.43 (CH), 127.98 (CH), 126.36
(quat), 125.08 (CH), 35.78 (CH2) and 17.67 (CH3); m/z (FAB)
247 (MHϩ, 100%).
A modified procedure was adopted for the preparation of
the 5-unsubstituted derivative 10. A solution of 4-amino-2,4-
dihydro-3H-1,2,4-triazole-3-thione 3 (0.25 g, 2.1 mmol) and
allyl bromide 6 (0.23 g, 2.1 mmol) in acetonitrile (10 cm3)
containing anhydrous potassium carbonate (0.40 g, 2.5 mmol)
was stirred at room temperature for 21 h. The inorganic salts
were removed by filtration, the filtrate was concentrated in
vacuo at room temperature or below, ethanol (10 cm3) was
added and the mixture was filtered once more. On removal of
the solvent 4-amino-3-allylthio-4H-1,2,4-triazole 10 (0.26 g,
79%), was obtained mp 83–85 ЊC (from ethanol) (Found, C,
37.9; H, 4.65; N, 34.8. C5H8N4Sؒ0.2 H2O requires C, 37.6; H,
5.3; N, 35.1%. Found, Mϩ,156.0469. C5H8N4S requires M
156.0470); δH ([2H]6DMSO) 8.46 (1H, s), 6.08 (2H, s), 5.95
(1H, m), 5.24 (1H, m), 5.07 (1H, m) and 3.77 (2H, m); δC
150.40 (quat), 146.39 (CH), 133.72 (CH), 118.44 (CH2) and
34.15 (CH2); m/z 156 (Mϩ, 37%), 141 (25), 129 (20) 56 (80)
and 41 (100).
m/z 139 (Mϩ, 100%), 98 (73), 71 (51) and 58 (57).
The triazole 10 (0.14 g, 1.0 mmol) was pyrolysed at 850 ЊC
(0.01 Torr) (inlet temperature 120 ЊC). The pyrolysate was
distilled to give [1,3]thiazolo[3,2-b][1,2,4]triazole13 25 as a pale
yellow solid, (0.055 g, 55%), bp 50–55 ЊC (4 Torr) mp 96–98 ЊC
6
3
(lit.,13 98–100 ЊC); δH 8.15 (1H, d, J 1.4), 7.81 (1H, d, J 4.4)
3
6
and 6.91 (1H, dd, J 4.4 and J 1.4); δC 156.34 (CH and quat),
119.86 (CH) and 113.85 (CH); m/z 125 (Mϩ, 100%), 98 (49), 71
(53) and 45 (65).
4-Amino-3-(2-methylprop-2-enyl)thio-5-methyl-4H-1,2,4-tri-
azole 12 (0.20 g, 1.1 mmol) was pyrolysed at an inlet temper-
ature of 130 ЊC and furnace temperature of 850 ЊC over a period
of 1 h. The pyrolysate was collected in DCM, and distilled to
give 2,5-dimethyl[1,3]thiazolo[3,2-b][1,2,4]triazole 24 as a pale
yellow liquid (0.08 g, 48%), bp 85 ЊC (2 Torr) (Found, Mϩ
153.0363. C6H7N3S requires M 153.0361); δH 7.41 (1H, q,
4
4J 1.4), 2.48 (3H, s) and 2.45 (3H, d, J 1.4); δC 165.13 (quat),
156.00 (quat), 126.40 (quat), 116.34 (CH), 14.68 (CH3) and
13.94 (CH3); m/z 153 (Mϩ, 100%), 112 (58) and 59 (95).
4-Amino-3-(but-2-enylthio)-5-methyl-4H-1,2,4-triazole 13
(0.20 g, 1.1 mmol) was pyrolysed at an inlet temperature of
135 ЊC and a furnace temperature of 850 ЊC over a period of 0.5
h. The pyrolysate was collected in DCM, and distilled to give
2,6-dimethyl[1,3]thiazolo[3,2-b][1,2,4]triazole14,15 26 as a pale
yellow liquid (0.09 g, 54%), bp 90 ЊC (2 Torr) [lit.,14 112–114 ЊC
(5 Torr); mp14 62–64 ЊC] (Found, Mϩ 153.0355. C6H7N3S
4
requires M 153.0361); δH 6.50 (1H, q, J 1.3), 2.53 (3H, s) and
2.50 (3H, d, 4J 1.3); δC (quaternaries not reported) 106.11 (CH),
14.77 (CH3) and 12.32 (CH3); m/z 153 (Mϩ, 100%), 112 (48), 67
(98) and 42 (69).
4-Amino-3-allylthio-5-phenyl-4H-1,2,4-triazole 15 (0.10 g,
0.4 mmol) was pyrolysed at an inlet temperature of 135 ЊC
and a furnace temperature of 850 ЊC over a period of 1 h. The
pyrolysate was collected in DCM, and distilled to give
2-phenyl[1,3]thiazolo[3,2-b][1,2,4]triazole9 27 as a pale yellow
liquid (0.02 g, 23%), bp 75 ЊC (0.7 Torr) which crystallised, mp
114–116 ЊC (lit.,9 118–119 ЊC) (Found Mϩ 201.0360. C10H7N3S
requires M 201.0361); δH 8.15 (2H, m), 7.81 (1H, d, J 4.5), 7.44
(3H, m) and 6.99 (1H, d, J 4.5); δC 167.35 (quat), 157.40 (quat),
130.92 (quat), 129.66 (CH), 128.60 (CH), 126.53 (CH), 119.92
(CH) and 112.95 (CH); m/z 201 (Mϩ, 100%), 116 (26), 103 (41)
and 76 (33).
4-Amino-3-(2-methylprop-2-enyl)thio-5-phenyl-4H-1,2,4-tri-
azole 16 (0.20 g, 0.8 mmol) was pyrolysed at a furnace temper-
ature of 750 ЊC with an inlet temperature of 130 ЊC over a period
of 1 h. The pyrolysate was collected in DCM, and distilled to
give 5-methyl-2-phenyl[1,3]thiazolo[3,2-b][1,2,4]triazole 28 as
a pale yellow liquid (0.08 g, 48%), bp 85 ЊC (2 Torr) mp 126–
128 ЊC (Found, Mϩ 215.0512. C11H9N3S requires M 215.0517);
δH 8.37 (2H, m), 7.77 (1H, q, 4J 1.4), 7.75 (3H, m) and 2.74 (3H,
d, 4J 1.4); δC (quaternary signals not quoted) 129.43 (CH),
128.55 (CH), 126.39 (CH), 116.56 (CH) and 14.10 (CH3); m/z
215 (Mϩ, 31%), 169 (46), 128 (43), 104 (58), 77 (47) and 55
(100).
Flash vacuum pyrolysis of 4-amino-3-allylthio-4H-1,2,4-triazoles
10–13 and 15–17
The aminotriazoles 10–13 and 15–17 were distilled at a pressure
of ca. 1 × 10Ϫ2 Torr into an empty silica furnace tube which was
maintained at the stated temperature by an electrically heated
furnace. The products were trapped in a U-tube cooled with
liquid nitrogen, and were washed from the trap with solvent at
the end of the pyrolysis.
When 4-amino-3-allylthio-5-methyl-4H-1,2,4-triazole 11
(0.30 g, 1.8 mmol) was sublimed at 120 ЊC over a period of 1.5 h
into the furnace tube at a temperature of 650 ЊC a mixture
of products was obtained, which was separated by dry flash
chromatography (silica), hexane–ethyl acetate (6:1), to give 2-
allyl-4-amino-5-methyl-2,4-dihydro-3H-1,2,4-triazole-3-thione
18 as a pale yellow liquid, (0.10 g, 33%) (Found, Mϩ 170.0623.
C6H10N4S requires M 170.0626); δH 5.85 (1H, m), 5.28 (2H, m),
4.72 (2H, m), 4.65 (2H, s) and 2.37 (3H, s); δC 165.99 (quat),
148.66 (quat), 130.53 (CH), 119.23 (CH2), 51.55 (CH2) and
10.37 (CH3); m/z 170 (Mϩ, 80%), 155 (64), 102 (45), 74 (42) and
56 (100).
4-Amino-3-(but-2-enylthio)-5-phenyl-4H-1,2,4-triazole 17
(0.20 g, 0.8 mmol) was pyrolysed at an inlet temperature of
135 ЊC and a furnace temperature of 750 ЊC over a period of 0.5
h. The pyrolysate was collected in DCM, and distilled to give
6-methyl-2-phenyl[1,3]thiazolo[3,2-b][1,2,4]triazole9,13 29 as a
pale yellow liquid which was contaminated with benzonitrile.
Dry-flash chromatography on silica gave 29 (0.09 g, 54%), bp
90 ЊC (2 Torr) (mp lit.,9 125–126 ЊC) (Found, Mϩ 215.0513.
C11H9N3S requires M 215.0517); δH 8.16 (2H, m), 7.46 (3H, m),
4
4
The triazole 11 (0.30 g, 1.8 mmol) was pyrolysed using the
same conditions as above, but at a furnace temperature of
850 ЊC. The pyrolysate was distilled to give 2-methyl[1,3]-
thiazolo[3,2-b][1,2,4]triazole9 19 as a golden liquid (0.14 g,
6.57 (1H, q, J 1.4) and 2.58 (3H, d, J 1.4); δC (quaternary
signals not reported) 129.56 (CH), 128.56 (CH), 126.56 (CH),
106.98 (CH) and 12.52 (CH3); m/z 215 (Mϩ, 100%), 144 (25),
103 (50) and 72 (52).
J. Chem. Soc., Perkin Trans. 1, 2001, 424–428
427

View Article Online
5-Methyl-4-(pyrrol-1-yl)-3-allylthio-4H-1,2,4-triazole 31
36.92 (CH2) and 9.13 (CH3); m/z 270 (Mϩ, 11%), 156 (33) and
91 (100).
The aminotriazole 11 (2.55 g, 0.015 mol), 2,5-dimethoxy-
tetrahydrofuran (1.9 cm3, 0.015 mol) and acetic acid (50 cm3)
were heated under reflux for 30 min. The solvent was removed
in vacuo to give a dark brown liquid, which solidified overnight
to give 5-methyl-4-(pyrrol-1-yl)-3-allylthio-4H-1,2,4-triazole 31
as a brown solid (2.91 g, 87%), mp 61–62 ЊC (from hexane)
(Found, C, 54.3; H, 5.4; N, 25.25. C10H12N4S requires C, 54.55;
H, 5.45; N, 25.25%); δH 6.70 (2H, t, J 4.5), 6.33 (2H, t, J 4.5),
5.91 (1H, m), 5.14 (2H, m), 3.76 (2H, m) and 2.24 (3H, s);
δC 152.38 (quat), 151.02 (quat), 132.04 (CH), 120.72 (CH),
119.16 (CH2), 109.77 (CH), 34.99 (CH) and 9.31 (CH3); m/z 220
(Mϩ, 56%), 173 (97) and 124 (100).
Flash vacuum pyrolysis of the 1,2,4-triazoles 31–33
The triazole 31 (0.20 g, 1 mmol) was sublimed at 160 ЊC (0.05
Torr) into the furnace tube which was maintained at a temper-
ature of of 750 ЊC. The pyrolysate was dissolved in dichloro-
methane and subjected to dry-flash chromatography on silica
(3:1 hexane–ethyl acetate) to give 2-methyl[1,3]thiazolo[3,2-b]-
[1,2,4]triazole9 19 (0.02 g, 15%) whose spectra were compatible
with those reported above.
Pyrolysis of 32 or 33 (inlet temperatures 180 ЊC) at 650–
750 ЊC (0.004–0.008 Torr) gave complex pyrolysates from which
the presence of bibenzyl could be inferred from their 1H NMR
spectra (δH 2.85). No cyclisation products could be detected.
4-Amino-3-benzylthio-5-methyl-4H-1,2,4-triazole 32
4-Amino-5-methyl-2,4-dihydro-3H-1,2,4-triazole-3-thione
4
Acknowledgements
We are grateful to Kodak Ltd. for a Research Studentship
(to D. D. J. C.).
(1.95 g, 0.015 mol) was added to DMF (50 cm3) containing
potassium carbonate (1.88 g, 0.015 mol). Benzyl chloride (1.89
g, 0.015 mol) was added dropwise with stirring then the mixture
was stirred at room temperature for 21 h. The insoluble potas-
sium carbonate was removed by filtration, then the filtrate con-
centrated in vacuo to give a pink solid. The solid was treated
with dichloromethane (20 cm3), the mixture filtered once more
and the solvent was removed in vacuo to give 4-amino-3-
benzylthio-5-methyl-4H-1,2,4-triazole 32 as an orange–brown
solid (0.65 g, 20%), mp 149–150 ЊC (from toluene) (Found, Mϩ
220.0785. C10H12N4S requires M 220.0783); δH 7.25 (5H, m),
4.20 (2H, s), 3.93 (2H, s) and 2.33 (3H, s); δC 153.58 (quat),
149.48 (quat), 137.27 (quat), 128.71 (CH), 128.67 (CH), 127.89
(CH), 38.97 (CH2) and 10.32 (CH3); m/z 220 (Mϩ, 21%), 106
(45) and 91 (100).
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428
J. Chem. Soc., Perkin Trans. 1, 2001, 424–428