Structural elucidation of propargylated products of 3-substituted-1,2, 4-triazole-5-thiols by NMR techniques

Article abstract of DOI:10.1002/mrc.2307

Propargylation of 3-substituted-1,2,4-triazole-5-thiols, which predominantly exist as their thione tautomers, was carried out with the view to synthesize different heterocycles and study their biological activity. Three different products namely, a mono S-propargyl and two S,N-dipropargyl regioisomers, arising from N1/N2 substitution, were isolated and characterized. Unambiguous structural elucidation of the regioisomers of S,N-dipropargyl derivatives was achieved by means of ¹³C-¹H HMBC technique. The proportion of the regioisomers was found to vary with the substituent on the 1,2,4-triazole thiols. No product corresponding to N4 substitution was isolated from any of the reactions carried out. Copyright

Full text of DOI:10.1002/mrc.2307

Spectral Assignments and Reference Data
Received: 8 May 2008
Revised: 19 July 2008
Accepted: 22 July 2008
Published online in Wiley Interscience: 13 October 2008
(www.interscience.com) DOI 10.1002/mrc.2307
Structural elucidation of propargylated
products of 3-substituted-1,2,
4-triazole-5-thiols by NMR techniques
Preeti M. Chaudhary,a Sayalee R. Chavan,a M. Kavitha,b
Shailaja P. Maybhate,a Sunita R. Deshpande,a Anjali P. Likhitea∗ and
P. R. Rajamohananb∗
Propargylation of 3-substituted-1,2,4-triazole-5-thiols, which predominantly exist as their thione tautomers, was carried out
with the view to synthesize different heterocycles and study their biological activity. Three different products namely, a
mono S-propargyl and two S,N-dipropargyl regioisomers, arising from N1/N2 substitution, were isolated and characterized.
Unambiguous structural elucidation of the regioisomers of S,N-dipropargyl derivatives was achieved by means of 13C–1H HMBC
technique. The proportion of the regioisomers was found to vary with the substituent on the 1,2,4-triazole thiols. No product
c
corresponding to N4 substitution was isolated from any of the reactions carried out. Copyright ꢀ 2008 John Wiley & Sons, Ltd.
Supporting information may be found in the online version of this article.
Keywords: NMR; 1H NMR; 13C NMR; 15N NMR; HMBC; 1,2,4-triazoles; regioisomers
Introduction
Experimental
Syntheses
1,2,4-Triazoles due to their unique structure and properties show
a wide range of biological activities such as antifungal,[1] plant
growth regulatory,[2] coronary dilatatory,[3] and broad-spectrum
antiviral[4] as well as anti-inflammatory[5] and antihypertensive[6]
pharmaceutical properties. The heteroaromatic 1,2,4-triazole can
exist in three different mesomeric structures.[7] Tautomerism in
1,2,4-triazole is well known because of the mobility of the proton
attached to ring nitrogen (prototropy).[8] In hydroxy-, thio- or
amino-substituted triazole derivatives the substituent donates a
proton to annular system and complicates prototropy further
leading to the formation of various regioisomers.
In alkylation reaction of 1,2,4-triazoles the N1 and N2 substi-
tution is preferred to N4 because of ‘α-diaza’ effect.[9] Alkylated
products such as the propargyl derivative of triazoles are key inter-
mediates for the synthesis of many biologically active heterocycles
like thiazolo-triazoles[10a] (1) and bistriazoles[10b] (2) (Scheme 1).
The encouraging biological activity of triazole nucleus and the use
of a new class of ‘enediyne’ compounds as DNA cleaving agents[11]
prompted us to synthesize new hybrid molecules in which aza-
heterocycles are coupled to diynes or alkynes such as a propargyl
moiety.
All the triazole thiols were prepared by following the reported
procedures (R = H,[13] Me,[14] t-Bu,[15] p-C6H4Cl,[16] and p-
C6H4OMe[16]).PropargylbromidewasobtainedfromSigmaAldrich
Chemicals Private Limited and was used as such.
Propargylation of 3-substituted-1,2,4-triazole-5-thiols
To a solution of 3-substituted-1,2,4-triazole-5-thiol (6.3 mmol) and
potassium carbonate (7.6 mmol) in dimethyl formamide (DMF)
(15 ml) propargyl bromide was added (7.6 mmol) drop wise and
the reaction mixture was stirred at room temperature for 4–6 h.
Completionofreactionwascheckedbythinlayerchromatography
(TLC). The solvent DMF was removed under vacuum and the
reaction mixture was partitioned between ethyl acetate and
water. Organic phase was washed with water, brine, dried over
sodium sulfate and concentrated to give a crude product. Column
chromatographic separation of the crude product on silica gel
furnished three different products.
∗
Correspondence to: Anjali P. Likhite, Division of Organic Chemistry, National
Chemical Laboratory, Dr. Homi Bhabha Road, Pune 411008, India
E-mail: ap.likhite@ncl.res.in
P. R. Rajamohanan Central NMR Facility, National Chemical Laboratory,
Dr. Homi Bhabha Road, Pune 411008, India.
We have earlier reported regiochemistry of phenacylation
in substituted 1,2,4-triazoles, where we observed the steric
factor playing a crucial role in entry of phenacyl group;[12] in
continuation of this work here we are addressing the reaction
of substituted 1,2,4-triazole thiols (3, Scheme 1) with propargyl
bromide. Multinuclear magnetic resonance techniques were used
for the structural elucidation of regioisomeric products obtained
in this reaction.
E-mail: pr.rajamohanan@ncl.res.in
a
DivisionofOrganicChemistry,NationalChemicalLaboratory,Dr.HomiBhabha
Road, Pune 411008, India
b
Central NMR Facility, National Chemical Laboratory, Dr. Homi Bhabha Road,
Pune 411008, India
c
Magn. Reson. Chem. 2008, 46, 1168–1174
Copyright ꢀ 2008 John Wiley & Sons, Ltd.

Spectral Assignments and Reference Data
O
N
N
S
R1
N
N
N
R
R
SH
N
R
N
N
N
NH
N
N
1
2
3
Scheme 1. Structure of compounds 1, 2, and 3.
HN N
N NH
N NH
HN NH
R
R
SH
R
R
S
SH
N
d
N
H
N
c
N
a
S
b
Br
K2CO3/DMF
R = 1) H, 2) Me, 3) t Bu 4) p-C6H4Cl, 5) p-C6H4OMe
X
N NH
N
N
HN N
N
N
N N
R
S
+
R
N
e
R
R
S
S
S
R
S
N
N
f
N
N
h
g
i
Scheme 2. Preparation of propargyl derivatives of 1,2,4-triazole thiols.
NMR techniques
(t1 increments) of four to eight scans were used for COSY and
NOESY measurements. The COSY and the HMBC spectra were
collected in a magnitude mode while a phase sensitive (States-
Time Proportionate Phase Increment (TPPI)) mode was used
for HSQC and NOESY measurements. A mixing time of 1 s was
employed for NOESY experiment. The number of scans used for
each t1 increment for other 2D experiments were as follows: 16
All the NMR measurements were carried out on a Bruker AV
400 MHz spectrometer operating at 400.13, 100.62, and 40.55 MHz
for1H,13C,and15Nnuclei,respectively.Thesamplesweredissolved
in a suitable solvent (CDCl3 or DMSO-d6) in a standard 5 mm
NMR tube and the 1H, COSY, NOESY, 13CCPD, 13C DEPT, 13C
off resonance, 13C–1H HSQC, 13C–1H HMBC, 15N DEPT, 15N–1H
HSQC and 15N–1H HMBC experiments were performed on 5 mm
broad band observe (BBO) gradient probe at ambient temperature
(∼28 ◦C). Gradient spectroscopic techniques were employed for
all the 2-D experiments. Two hundred and fifty six experiments
(
13C HSQC, 15N HSQC), 32 (13C HMBC), and 32/40 (15N HMBC). The
13C HMBC data were optimized for a long-range coupling constant
of 7 Hz whereas the corresponding 15N measurements were
conducted for delays corresponding to long-range couplings of 10
and 4 Hz. A pulse sequence employing a double low pass filter was
Table 1. 1H, 13C, and 15N NMR chemical shiftsa of 3-substituted-1,4-dihydro-1H,4H-1,2,4-triazol-5-thiones b1–b5
1H
2
3
1) R = H
2) R = Me
3) R = tBu
4) R = p-C6H4Cl
N
2N
3
5
1
4
X
S
4
N
H
R
5) R = p-C6H4OMe X = Cl, OMe
Atom position
Compound
1
2
3
4
5
R
1
2
3
4
δH 13.47 δN −175.5
δH 13.47 δN −176.6
δH 13.16 δN −179.5
δH 13.77 δN −174.7
δN −98.2
δC 140.89
δC 149.3
δH 13.26 δN −206.3
δH 13.00 δN −204.0
δH 13.12 δN −210.4
δH 13.95 δN −212.5
δC 165.88
δC 166.31
δC 166.88
δC 167.61
δH 8.22
δN −104.7
δN −107.7
δN −104.3
δHMe 2.14 δCMe 11.28
δC 159.95
δC 149.74
δH Me3 1.22 δC 31.83 δCMe3 28.30
δH2 7.92 δH3 7.57 δC1 124.79 δC2 129.66 δC3
127.90 δC4 135.69
5
δH 13.58 δN −175.8
δN −108.9
δC 150.58
δH 13.71 δN −213.4
δC 167.06
δH2 7.85 δH3 7.04 δHOMe 3.79 δCOMe 55.83 δC1
118.33 δC2 127.80 δC3 114.94 δC4 161.40
a Solvent: DMSO-d6.
c
Magn. Reson. Chem. 2008, 46, 1168–1174
Copyright ꢀ 2008 John Wiley & Sons, Ltd.
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P. M. Chaudhary et al.
Table 2. 1H, 13C and 15N NMR chemical shifts of 3-substituted-5-(prop-2-ynylthio)-1H-1,2,4-triazoles e1–e5
1
1
2
3
H
3
1) R = H
2) R = Me
3) R = tBu
4) R = p-C6H4Cl
2
R1
N
2N
1
4
R1 =
X
S
5
3
N
R
4
X = Cl, OMe
5) R = p-C6H4OMe
Atom position
Compound
1a
2a,b
3
4
5
R
R1
c
c
c
c
1
δH 14.13
δN −173.6
δH 13.68
δN −169.2
δH 13.68
δN −101.6 δC 146.19 δN
δN −132.2 δC 155.33 δN
δC 155.96 δH 8.06
δC 156.53 δHMe 2.46 δCMe 11.12
δH1 3.68 δH3 2.16 δC1 20.65 δC2 78.67
δC3 71.76
–
2
3
4
δH1 3.82 δH3 2.20 δC1 20.18 δC2 78.58
δC3 71.46
–
–
–
δN −102.1 δC 167.10 δN
δC 157.31 δHMe3 1.35 δC 32.48 δCMe3 29.10
δH1 3.81 δH3 2.18 δC1 20.91 δC2 79.2
δC3 71.71
δN −174.2
c
δH −14.6, 14.3
δN −174.7,
−169.0
δN
δC 158.36 δN
δC 158.32 δH2 7.89 δH3 7.38 δC1 126.8 δC2
127.73 δC3 129.13 δC4 136.19
δH1 3.90 δH3 2.25 δC1 20.22 δC2 78.85
δC3 72.08
–
c
c
5
δH 14.37
δN
δC 158.24 δN
δC 157.04 δH2 7.90 δH3 6.93 δHOMe 3.84 δCOMe
55.39 δC1 119.85 δC2 128.15 δC3
113.92 δC4 161.43
δH1 3.92 δH3 2.26 δC1 21.16 δC2 71.96
δC3 79.17
–
–
δN −176.6
a Solvent: DMSO-d6. All the other chemical shifts presented in the Table were measured in CDCl3 –Methanol-d4 (4 : 1 v/v) mixture.
b 15N chemical shifts have been extracted from the HSQC/HMBC spectrum.
c 1H–15N HSQC/HMBC correlations could not be observed.
found to give better results for 13C HMBC because of considerable
spread in JC–H values (140–250 Hz). The HMBC spectra were
1,2,4-triazole thiols with propargyl bromide under mild alkaline
conditions (K2CO3/DMF, at 28 ◦C) furnished three products which
were separated by column chromatography and were identified
by multinuclear 1-D (1H, 13C, and 15N) and 2-D (NOESY, HMBC, and
HSQC) magnetic resonance studies as S-propargyl (e and f) and
S,N-dipropargyl (g and h) derivatives (Scheme 2).
1
acquired without proton decoupling during detection. The 90◦
pulse lengths for 1H, 13C, and 15N were 13.5, 10, and 14 µs,
respectively. Appropriate window functions, viz. sine squared bell
with no phase shift for all magnitude modes and phase shifted
(ssb = 2) sine-squared bell for phase sensitive mode were used for
data processing. In general a 1 K×1 K data matrix size was used for
the2-Dexperiments. Allthethiolsb1–b5weredissolvedinDMSO-
d6 while two solvents, viz. (i) CDCl3-Methanol-d4 mixture (4 : 1 v/v)
and (ii) DMSO-d6 were used for the mono-propargylated products
e1–e5, and the di-substituted products g1–g5 and h1–h5 were
The S-propargylated compounds (Scheme 2) can exist in
two tautomeric forms, i.e. 3-substituted-5-(prop-2-ynylthio)-1H-
1,2,4-triazoles (e) and 5-substituted-3-(prop-2-ynylthio)-1H-1,2,4-
triazoles (f). In DMSO solution all the S-propargylated compounds
showed strongly deshielded proton signal arising from the NH
in the ring. In some of the cases (R = H, t-Bu) the NMR signals
were found to be broad with more than one environment due
to the tautomeric equilibrium between e and f which is, further
supportedbypositiveexchangecrosspeaksintheirNOESYspectra
(Supporting Information, Section B, Figs 2,5,7,10 and 16). In the
cases where the rate of interconversion between the tautomers is
slow (R = t-Bu and p-C6H4OMe), one could even find NH proton
HMBC connectivities to both the carbons in the heterocyclic
ring and such a connectivity could not be seen to the carbon
on the substituent R (Supporting Information, Section B, Figs 8
and 17). This indeed suggests that the dominant tautomer is e.
The comparison of the chemical shifts of various S-propargylated
products is given in Table 2.
1
dissolved in CDCl3. The H chemical shifts were referred to the
residual solvent peak (δ = 7.28 ppm for CDCl3 and 2.50 ppm for
DMSO-d6) and for 13C the central signals of the solvents were
used for referencing (δ = 77.0 ppm for CDCl3 and 39.95 ppm for
DMSO-d6). The 15N chemical shifts were referred to an external
sample of nitromethane (δ = 0 ppm).
Results and Discussion
The tautomeric equilibrium in 1,2,4-triazole thiols has been a
subject of many theoretical[17] and experimental investigations[18]
which showed the predominance of the thione form over the
thiol. Presence of tautomer b (Scheme 2) had been proposed
for the case R = H[18b] and 15N chemical shifts observed for the
various compounds studied here were very close to the reported
values for this compound. Hence, we also believe that the form
b (3-substituted-1,4-dihydro-1H,4H-1,2,4-triazol-5-thione) is the
dominant tautomer present in the cases studied here (Supporting
Information, Section A). The chemical shift details of the thiones
used in the present investigation are presented in Table 1.
1
The one-dimensional H and 13C NMR spectra by themselves
were not enough to differentiate the two regioisomers (g and h)
of the di-propargylated products though they showed different
chemical shifts (Supporting Information, Section D, Tables 6,7
and 8). In some of the cases studied the COSY and NOESY
experiments provided information about the position of the
second propargyl group in the di-propargylated regioisomers
(Supporting Information, Section C, Figs, 3,6,7,10 and 13). In
general, the N-CH2 protons in all the products corresponding
to the more polar regioisomer showed strong NOESY cross peak
withtheprotonsonsubstituentRwhichindicatedthattheproduct
obtained was of the type g or i. Differentiation between these two
Reaction of 1,2,4-triazole-5-thiols with propargyl bromide in
neutral condition gave S-propargylated product in quantitative
yield.[10a] While, we observed that, propargylation of substituted
c
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Spectral Assignments and Reference Data
Figure 1. Comparison of the 13C–1H HMBC spectrum of the of the reaction products of R = Me case. (a) Mono S-propargylated product 2e,
(b) di-propargylated regioisomer 2g, and (c) di-propargylated regioisomer 2h.
Figure 2. Comparison of the 15N–1H HMBC spectrum of the of the reaction products of R = Me. (a) Di-propargylated regioisomer 2h and
(b) di-propargylated regioisomer 2g.
c
Magn. Reson. Chem. 2008, 46, 1168–1174
Copyright ꢀ 2008 John Wiley & Sons, Ltd.
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P. M. Chaudhary et al.
Table 3. 1H, 13C, and 15N NMR chemical shiftsa of 5-substituted-1-(prop-2-ynyl)-3-(prop-2-ynylthio)-1H-1,2,4-triazoles g1–g5
2
3
1
2
N
3
2
1) R = H
2) R = Me
3) R = tBu
R2
1
N
R1
1
4
R1, R2
=
X
S
3
5
4) R = p-C6H4Cl
5) R = p-C6H4OMe
N
X = Cl, OMe
R
4
Atom position
Comp
1
2b
3
4b
5
R
R1
R2
1
δN −185.0
δN −108.9
δC 160.10
δC 153.67
δC 156.91
δC 159.25
δN −145.4
δN −140.5
δC 143.96
δH 8.22
δH1 3.82 δH3 2.20
δC1 20.27 δC2
79.41 δC3 71.39
δH1 4.90 δH3 2.60
δC1 39.68 δC2
74.76 δC3 76.23
2
3
4
δN −185.1
δN −191.5
δN −173.6
δN −103.3
δN −104.8
δN −89.2
δC 157.81
δC 163.36
δC 155.02
δHMe 2.47 δCMe
12.03
δH1 3.81 δH3 2.20
δC1 20.21 δC2
79.42 δC3 71.34
δH1 4.83 δH3 2.45
δC1 38.38 δC2
75.57 δC3 74.59
δN −144.7
δHMe3 1.46 δC
32.82 δCMe3
29.16
δH1 3.87 δH3 2.21
δC1 20.14 δC2
79.38 δC3 71.13
δH1 4.87 δH3 2.44
δC1 40.24 δC2
76.85 δC3 74.25
c
δN
δH2 7.75 δH3 7.52
δC1 125.32 δC2
129.98 δC3
δH1 3.95 δH3 2.25
δC1 20.22 δC2
79.30 δC3 71.41
δH1 4.94 δH3 2.54
δC1 39.63 δC2
76.46 δC3 75.00
–
129.42 δC4
137.10
c
5
δN −174.3
δN −91.8
δC 158.78
δN
δC 155.98
δH2 7.69 δH3 7.01
δHOMe 3.85
δCOMe 55.45 δC1
119.08 δC2
δH1 3.93 δH3 2.23
δC1 20.22 δC2
δH1 4.90 δH3 2.52
δC1 39.48 δC2
–
79.44 δC3 71.41
76.85 δC3 74.46
130.16 δC3
114.05 δC4
161.43
a Solvent : CDCl3.
b 15N Chemical shifts have been extracted from the HSQC/HMBC spectrum.
c 1H–15N HSQC/HMBC correlations could not be observed.
1
regioisomers was not possible by H NMR alone and required a
The 1H–15N HMBC experiment can corroborate the results
obtained from 13C and 1H NMR. The three nitrogen atoms present
in these molecules appear in the region δ = −90 to −190 ppm.
The ‘pyridine’ type (sp2) nitrogen signals are usually deshielded
compared to the ‘pyrrole’ type (sp3) one. The nitrogen on which
the propargyl substituent is present will always be of the ‘pyrrole’
type and hence will appear at a higher field. In the product g
(R = Me) 1H–15N HMBC correlations between the methyl protons
and the adjacent N1 and N4 nitrogens were observed. When
R = H, correlation of these protons to all the three nitrogen
atoms could be seen (Supporting Information). Because of very
weak four-bond coupling, correlation between the protons on
the substituent R and the ring nitrogens could not be seen for
R = t-Bu, p-C6H4Cl, and p-C6H4OMe under the measurement
conditions. But, a correlation of the N-CH2 protons to N1 and N2
atoms is always present as shown in Fig. 2.
detailed investigation through 13C–1H HMBC experiment.
A comparison of the 13C–1H HMBC spectra of the C3–C5
region (δ = 145–160 ppm) of the mono S-substituted product
and the di-substituted product corresponding to the more polar
regioisomer showed that, the C3 carbon of the mono-substituted
product showed connectivity only to the S-CH2 carbon except for
the case R = H where it showed correlation to H5 proton also
(Supporting Information, Section C, Fig 4). The C5 carbon always
showed correlation to the N-CH2 protons and to protons on R
(R = Me, t-Bu, p-C6H4Cl, and p-C6H4OMe) except for the case
R = H. These results clearly demonstrate that the products formed
are the ones in which the propargyl substituent is on N1 or N4.
The absence of HMBC cross peak between the N-CH2 protons and
the carbons in the heterocyclic ring (C3 and C5) confirms that the
structure of the product is g.
In the 13C–1H HMBC spectrum of the less polar product, in
all the cases studied, the ring carbon attached to the thio group
correlated always with both the N-CH2 and S-CH2 protons. In the
case of R = H, this carbon showed an additional correlation to
the ring proton also (Supporting Information, Section C, Fig 4)
(δ = 8.22 ppm). The 1,2,4-triazole ring carbon, to which the R
group was attached, exhibited HMBC connectivity only to the
protons on the R group (except for R = H). Thus, this type of
regioisomer formed can be identified as h. Here also, the N4
substitution can be ruled out as the N-CH2 protons did not show
any HMBC connectivity to C3 and C5 carbons. A comparison of the
13C HMBC spectra of a typical mono-substituted product (R = Me)
with that of the di-substituted products is shown in Fig. 1.
Similar correlations have also been observed for regioisomer h.
The N1, N2, and N4 chemical shifts of these two regioisomers, for
a particular substituent, are found to be very similar. The chemical
shift details of regioisomers g and h are presented in Tables 3 and
4, respectively.
We have noticed that in unsubstituted-1,2,4-triazole thiol
(R = H) the di-propargylated products g and h were obtained
nearly in 4 : 1 ratio and when R = t-Bu the ratio of g and h was
found to be reversed. The regioisomer g was found to decrease
with the increasing bulkiness of the substituent (1–5) (Supporting
Information, Section C, Fig 5). N4 propargylated product was not
at all obtained in these reactions. When R is aromatic the S-
propargylated product is either not isolated or obtained in very
c
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Spectral Assignments and Reference Data
Table 4. 1H, 13C, and 15N NMR chemical shiftsa of 3-substituted-1-(prop-2-ynyl)-5-(prop-2-ynylthio)-1H-1,2,4-triazoles h1–h5
R2
2
3
1
1
3
2
1) R = H
2) R = Me
3) R = tBu
4) R = p-C6H4Cl
5) R = p-C6H4OMe
2
N
R1
N
1
4
R1, R2 =
X
S
5
3
N
X = Cl, OMe
R
4
Atom position
5
Comp
1
2b
3
4
R
R1
R2
1
δN −187.9
δN −96.3
δC 151.81
δC 161.36
δC 172.30
δC 161.43
δN −142.9
δC 150.20
δC 149.70
δC 149.12
δC 150.98
δH 7.88
δH1 3.90 δH3 2.26
δC1 22.37 δC2
78.21 δC3 72.63
δH1 4.90 δH3 2.46
δC1 38.49 δC2
75.48 δC3 74.78
2
3
4
δN −190.3
δN −190.8
δN −170.8
δN −103.7
δN −103.4
δN −87.7
δN −151.9
δHMe 2.31 δCMe
14.04
δH1 3.85 δH3 2.25
δC1 22.56 δC2
78.21 δC3 72.71
δH1 4.83 δH3 2.43
δC1 38.17 δC2
75.86 δC3 74.38
c
δN
δHMe3 1.32 δC
33.04 δCMe3
29.35
δH1 3.89 δH3 2.25
δC1 22.82 δC2
78.35 δC3 72.55
δH1 4.90 δH3 2.43
δC1 38.25 δC2
76.20 δC3 74.25
–
c
δN
δH2 8.03 δH3 7.40
δC1 129.01 δC2
128.76 δC3
δH1 4.02 δH3 2.31
δC1 22.76 δC2
78.20 δC3 72.79
δH1 4.90 δH3 2.46
δC1 38.68 δC2
75.72 δC3 74.72
–
127.68 δC4
135.35
c
5
δN −172.2
δN −90.1
δC 162.3
δN
δC 150.39
δH2 8.03 δH3 6.95
δHOMe 3.85
δH1 4.01 δH3 2.31
δC1 22.84 δC2
δH1 4.99 δH3 2.48
δC1 38.56 δC2
–
δCOMe 55.45 δC1
123.22 δC2
127.83 δC3
113.92 δC4
160.69
78.33 δC3 72.75
76.00 δC3 74.50
a Solvent : CDCl3.
b 15N Chemical shifts have been extracted from the HSQC/HMBC spectrum.
c 1H–15N HSQC/HMBC correlations could not be observed.
the mono S-propargylated derivatives, which predominantly exist
as3-substituted-5-(prop-2-ynylthio)-1H-1,2,4-triazoletautomer(e)
andregioisomersoftheS,N1/N2di-propargylatedproductsidenti-
fied as 5-substituted-1-(prop-2-ynyl)-3-(prop-2-ynylthio)-1H-1,2,4-
triazole (g) and 3-substituted-1-(prop-2-ynyl)-5-(prop-2-ynylthio)-
1H-1,2,4-triazole (h). The proportion of the products formed was
found to change with the substituent on the triazole ring. Forma-
tion of any S,N4 di-substituted product (i) has not been noticed.
Table 5. The profile of the products formed in the reaction between
3-substituted 1,2,4-triazole thiones and propargyl bromide in DMF
Product
Serial
no.
R
e/f
g
h
1
2
3
4
5
H
Me
22
29
33
0
63
50
13
34
34
15
21
54
66
58
t-Bu
Supporting information
p-C6H4Cl
p-C6H4OMe
8
Supporting information may be found in the online version of this
article.
lowyield.InsuchcasestheS-propargylatedproductforthepresent
study has been prepared by the method given by Heravi et al.[10a]
The product distribution for the reaction with various substituents
is given in Table 5.
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Copyright ꢀ 2008 John Wiley & Sons, Ltd.
Magn. Reson. Chem. 2008, 46, 1168–1174