Br?nsted/Lewis acids-promoted selective preparations of 3-hetero quinolines or 4/5-hetero triazoles from azides and hetero-alkynes

Article abstract of DOI:10.1016/j.tet.2017.05.076

Selective preparations of hetero-quinoline and triazole derivatives, which were determined by the addition of a Br?nsted acid or a Lewis acid, were herein demonstrated. High regio-selectivity was observed over the reactions of alkynyl phosphonates, while alkynyl sulfides offered high efficiency. And various six or five-membered aza-cyclic compounds were successfully furnished in high yields (up to 94%) and good functional group compatibility (up to 39 examples).

Full text of DOI:10.1016/j.tet.2017.05.076

Accepted Manuscript
BrØnsted/Lewis acids-promoted selective preparations of 3-hetero quinolines or 4/5-
hetero triazoles from azides and hetero-alkynes
Ping Huang, Qiong Su, Wanrong Dong, Yingjun Zhang, Delie An
PII:
S0040-4020(17)30577-X
10.1016/j.tet.2017.05.076
TET 28742
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 10 April 2017
Revised Date: 20 May 2017
Accepted Date: 23 May 2017
Please cite this article as: Huang P, Su Q, Dong W, Zhang Y, An D, BrØnsted/Lewis acids-promoted
selective preparations of 3-hetero quinolines or 4/5-hetero triazoles from azides and hetero-alkynes,
Tetrahedron (2017), doi: 10.1016/j.tet.2017.05.076.
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BrØnsted/Lewis acids-promoted selective
preparations of 3-hetero quinolines or 4/5-
hetero triazoles from azides and hetero-
alkynes
Ping Huanga,§, Qiong Sua,§, Danyang Qi,a Wenkang Song,a Wanrong Donga,*, Yingjun Zhangb,* and Delie Ana,*
aState Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical
Engineering, Hunan University, Lushan South Rd. 2, Changsha, 410082, P.R. China
wanrongdong@hnu.edu.cn; deliean@hnu.edu.cn;
bState Key Laboratory of Anti-Infective Drug Development (NO. 2015DQ780357), Sunshine Lake Pharma
Co.,Ltd, Dongguan 523871, P. R. China
ZhangYingjun@hec.cn.
§P. Huang and Q. Su devoted equally to the publication.
Selective preparations of hetero-quinoline and triazole derivatives, which were determined by the addition of a BrØnsted
acid or a Lewis acid, were herein demonstrated. High regio-selectivity was observed over the reactions of alkynyl
phosphonates, while alkynyl sulfides offered high effieciency. And various six or five-membered aza-cyclic compounds
were successfully furnished in high yields (up to 94%) and good functional group compatibility (up to 31 examples).

1
ACCEPTED MANUSCRIPT
Tetrahedron
journal homepage: www.elsevier.com
BrØnsted/Lewis acids-promoted selective preparations of 3-hetero quinolines or 4/5-
hetero triazoles from azides and hetero-alkynes
Ping Huanga,§, Qiong Sua,§, Wanrong Donga,*, Yingjun Zhangb,* and Delie Ana,*
aState Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan University, Lushan South Rd. 2,
Changsha, 410082, P.R. China
bState Key Laboratory of Anti-Infective Drug Development (NO. 2015DQ780357), Sunshine Lake Pharma Co.,Ltd, Dongguan 523871, P. R. China.
§P. Huang and Q. Su devoted equally to the publication.
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
Selective preparations of hetero-quinoline and triazole derivatives, which were determined by
the addition of a BrØnsted acid or a Lewis acid, were herein demonstrated. High regio-
selectivity was observed over the reactions of alkynyl phosphonates, while alkynyl sulfides
offered high effieciency. And various six or five-membered aza-cyclic compounds were
successfully furnished in high yields (up to 94%) and good functional group compatibility (up to
39 examples).
Available online
Keywords:
Trifluoromethyl sulfonic acid
Copper sulfate
2009 Elsevier Ltd. All rights reserved
.
Cyclization
Hetero-quinolines
Hetero-triazoles
substituted triazoles are still rare.[13] Herein, we would like to
reported the reactions between arylmethyl azides and alkynyl
phosphonates/sulfides for the formations of 3-hetero quinolines
or 1,2,3-triazolyl phosphonates/sulfides, which were determined
by the employment of the BrØnsted acid or the Lewis acid
(Scheme 1).
1. Introduction
Five or six-membered aza-cyclic molecules, for example,
quinoline or triazole derivatives, have attracted long-standing
research interests as one of the most prevalent core structures,
either in natural products or in synthetic intermediates.[1] Up to
date, great contributions have been devoted for the introduction
of hetero groups into quinoline or triazole molecules. Amongst,
phosphonation of quinolines focused mainly on the C2 position,
and preactivated quinolines such as 2-halo quinolines[2] or N-
oxide quinolines[3] were involved for the formation of C-P bonds.
Various transition metal-catalysts such as Ru(III),[4] Ag(I),[5]
Cu(II),[6] Ni(II)[7] or Fe(III)[8] are usually employed for the
construction of the 2-hetero quinolines through C-H or/and P-H
activation pathway. Meanwhile, facile transformations towards
C3-phosphonated quinolines are still severely required since the
literal description stays very limited.[9] Very recently, Tummatorn
has described a regioselective synthesis of 3-bromoquinolines by
acid-promoted rearrangement of arylmethyl azides.[10] As the
long-standing interests on the further applications of alkynyl
phosphonates, alkynyl sulfides,[11] we ran into an idea to form 3-
hetero-substituted quinolines directly from arylmethyl azides and
alkynyl phosphonates/sulfides in the presence of a BrØnsted acid.
Meanwhile, [3+2] cycloaddition reactions, such as "Click
Reaction" between alkynes and azides, which underwent by the
participation of some Lewis acids, especially the copper catalysts,
has been intensively investigated, leading to synthetic useful
intermediates triazole derivatives.[12] However, to the best of our
knowledge, documentations on the synthesis of hetero-
Coupling reactions
G
P(O)(OR)2
G
X
Ref. 2 - 9
N
N
(O)
Quinolines or
2/3-Halo quinolines
N-Oxide quinolines
P-(2-Quinolinyl) phosphonates
or
P-(3-Quinolinyl) phosphonates
Alkynyl bromide
TfOH
Br
N3
Ar
Ar
Cyclization
Azide Rearrangement
Ref. 10
N
3-Bromo quinolines
Alkynyl phosphonates
or sulfides
N
Hetero
N
N
Ar
N3
+
Ar
Ar
Selective cyclization
Hetero
Hetero
N
This work
3-Hetero-quinolines 4 or 5-Hetero triazoles
By Bronsted Acid By Lewis Acid
Scheme 1. Strategies towards hetero-quinolines or triazoles
2. Results and discussions
Initially, benzyl azide (1a) and dimethyl phenylethynyl
phosphonate (2a) were selected as the model substrates for the
optimization of the reaction conditions, which were summarized

2
Tetrahedron
[d,f]
in Table 1. The desired product P-(4-phenyl-3-quinolinyl)
ACCEPTED MANUSCRIPT TfOH (2.0)
14
DCE
81
dimethyl phosphonate (3a) was obtained under the TfOH
(trifluoromethyl sulfonic acid, 1.5 equivalents) and then DDQ
(2,3-dichloro-5,6-dicyano benzoquinone, 3.0 equivalents)-
mediated system at room temperature throughout, in 56% yield
(entry 1). And nitrogen atmosphere was required for the first step
in case the decomposition of the azide substrate. Increased
loading of the acid led to higher yield of the desired quinoline
skeleton derivative 3a, in 65% yield (entry 2). Amongst all the
solvents tested, DCE (1,2-dichloroethane) offered better
performance than others, like DCM (dichloromethane),
chloroform, tetrachloromethane, acetonitrile and DMF (dimethyl
formamide), since lower yield was obtained or even no reaction
was observed (entries 3 – 7). Subsequently, the activities of
various BrØnsted acids or Lewis acids were tested in the system.
Organic acids such as trifluoroacetic acid and methyl sulfonic
acid offered the desired phosphoryl adduct 3aa in poor yields,
15% and 23%, respectively (entries 8 and 9). But inorganic acids
like polyphosphoric acid or strong Lewis acid AlCl3 failed to
make the reaction happen, since no reaction was detected after ca.
12 h (entries 10 and 11). The results might root from the
depression for the rearrangement of benzyl azide, which
generated a key intermediate N-phenyl iminium ion in-situ, and
successive nucleophilic addition/annulation procedure in the less
acidic environment.[15] It was surprising to mention that if the
reaction was conducted in a one-pot manner, the yield of 3aa
increased to a satisfying 72% ratio (entry 12), overmatching the
results obtained by the use of trifluoro acetic acid and methyl
sulfonic acid (the yields in the parentheses for entries 8 and 9).
Higher temperature led decreased efficiency of the one-pot
[a] Conditions: 1) 1a (0.3 mmol), 2a (0.6 mmol), acid in solvent (3.0 mL)
under N2 for overnight (ca. 12 h), then 2) DDQ (3.0 equiv.) in EtOAc (2.0
mL); Isolated yields; c) stands for not detected; d) the result was obtained
b)
in a one-pot manner; e) at 60 oC instead of r.t.; f) air was used as the oxidant
instead of DDQ.
Successively, the substrate scope of the acid-mediated one-
pot reaction was further investigated as shown in Table 2. P-(2-
phenylethynyl)-P-diethyl phosphonate 1b reacted with benzyl
azide (2a) smoothly under the acid-participated and air-oxidated
conditions, furnishing the desired adduct 3ba in 80% yield (entry
1). In the same manner, alkynyl substituted diisopropyl
phosphonate 1c, dibutyl phosphonate 1d and diphenyl phosphite
1e underwent the cyclization reaction efficiently, offering the
desired products 3ca – 3ea successfully in yields ranging from
76% to 80% (entries 2 – 4). Next, effects of different substituents
on the alkynyl dimethyl phosphonates were checked under the
standard conditions. Electon-donating phenyl groups decorated
alkynyl dimethyl phosphonates performed effectively in the
system.
For P-[2-(4-methylphenyl) ethynyl]
dimethyl
phosphonate (1f), P-[2-(3-methylphenyl) ethynyl] dimethyl
phosphonate (1g), P-[2-(4-methoxylphenyl) ethynyl] dimethyl
phosphonate (1h) and P-[2-(3-methoxylphenyl) ethynyl]
dimethyl phosphonate (1i) reacted with 2a successfully, giving
the corresponding products 3fa – 3ia in yields from 81% to 89%
(entries 5 – 8). It was noteworthy that the substituents of the
electron-donating groups on the phenyl group did not affect the
effciency of the system by conparision of entries 5 and 7 with
entries 6 and 8. Meanwhile, halo groups such as chloro- and
bromo- substituted phenyl groups of dimethyl phosphonates 1j
and 1k offered the desired adducts 3ja and 3ka in slightly lower
yields, 79% and 82%, respectively (entries 9 and 10). Moreover,
to our satisfactory, polyaromatic fused 3-phosphonated
quinolines such as 4-(1-naphthyl) and 4-(1,1’-biphenyl)
substituted adducts 3la and 3ma were successfully furnished with
assistance of TfOH in good yields (87% and 83% for entries 11
and 12). Subsequently, the compatibilities of the functional
groups on the benzyl azides were also evaluated in the system, as
showed in Table 2. para-Methyl benzyl azide (2b) underwent the
cyclization reaction smoothly with dimethyl phosphonate 1a
under the acidic environment, offering the corresponding 3-
phosphonated adduct 3ab in 75% yield (entry 13). The
compatibility of the halo groups such as chloro- or bromo- were
evaluated and the desired hetero-quinolines 3ac and 3ad were
isolated in 76% and 74% yields, respectively (entries 14 and 15).
To our delight, electron-deficient benzyl groups, which were
exemplified by 4-cyano benzyl azide (2e) and 4-nitro benzyl
azide (2f), gave the desired products 3ae and 3af in 74% and
80% yields, separately (entries 16 and 17). Also, 2-
naphthylmethyl azide (2g) coupled with 1a, furnishing the
desired product 3ag in good yield (entry 18).
o
reaction for only 50% yield was obtained at 60 C for overnight
(entry 13). When air was introduced for the oxidative step instead
of DDQ, the desired adduct 3aa was successfully isolated in 81%
yield without pause of the reaction (entry 14).
Table 1. Optimization of the annulation reaction[a]
O
P
N
1) acid, Sol., N2, overnight, r.t.
N3
Ph
OMe
OMe
+
O
2) oxidant, r.t.
P
OMe
OMe
H
N
Ph
1a
2a
3aa
N-phenyl iminium ion
Entry
Acid (equiv.)
TfOH (1.5)
Solvent
DCE
Yield (%)[b]
56
1
2
TfOH (2.0)
DCE
65
3
TfOH (2.0)
DCM
CHCl3
CCl4
60
4
TfOH (2.0)
trace
trace
n.d.[c]
n.d.
5
TfOH (2.0)
6
TfOH (2.0)
CH3CN
DMF
DCE
Table 2. Substrate scope towards quinolinyl phosphonates[a]
7
TfOH (2.0)
8
CF3COOH (2.0)
CH3SO3H (2.0)
15 (23)[d]
23 (40)[d]
n.d.
9
DCE
10
11
12[d]
13[d,e]
Polyphosphoric acid (2.0)
AlCl3 (2.0)
DCE
Entry
3
Ar (R)
Ph (OEt)
Ph (OiPr)
Ph (OnBu)
Ar'
Ph
Ph
Ph
Ph
Ph
Yield (%)[b]
80%
1
2
3
4
5
3ba
3ca
3da
3ea
3fa
DCE
n.d.
76%
TfOH (2.0)
DCE
72
78%
Ph (Ph)
80%
TfOH (2.0)
DCE
50
4-MeC6H4 (OMe)
81%

3
were further explored as shown in Table 4. Phenyl
6
3ga
3ha
3ia
3-CH3C6H4 (OMe)
4-CH3OC6H4 (OMe)
3-CH3OC6H4 (OMe)
4-ClC6H4 (OMe)
4-BrC6H4 (OMe)
1-Naphthyl (OMe)
4-(1,1'-biphenyl) (OMe)
Ph (OMe)
Ph
Ph
85%
ACCEPTED MANUSCRIPT
phenylethynyl sulfide (5a) reacted with benzyl azide (2a)
successfully under the Cu(II)-catalytic conditions, offering the
corresponding isomers 6a and 7a in a combined 90% yield, but in
a 1:1 ratio without regioselectivity (entry 1). At the same time, 4-
7
89%
82%
79%
82%
87%
83%
75%
76%
74%
74%
80%
8
Ph
9
3ja
Ph
10
11
12
13
14
15
16
17
3ka
3la
Ph
methylphenylethynyl
phenyl
sulfide
(5b)
and
4-
Ph
methoxyphenylethynyl phenyl sulfide (5c) cyclized with azide
(2a) and the desired adducts 6b (7b) and 6c (7c) in good yields,
up to 93% yields (entries 2 and 3). Halo groups substituted
substrates were also well-tolerated in the triazole-forming system,
and the products were isolated in yields up to 94% ratio (entries 4
and 5). The compatibilities of the polyaromatic group and
aliphatic group, which were exemplified by 2-naphthyl and ethyl
group, were also tested. Again, the results indicated that the
system exhibited high efficiency, but in poor regioselectivity
(entries 6 and 7).
3ma
3ab
3ac
3ad
3ae
3af
Ph
4-CH3C6H3
4-ClC6H3
4-BrC6H3
4-NCC6H3
4-NO2C6H3
Ph (OMe)
Ph (OMe)
Ph (OMe)
Ph (OMe)
18
3ag
83%
a) Conditions: 1a (1.0 mmol), 2a (2.0 mmol), triflate acid (2.0 equiv.) in DCE
(5.0 mL) under N2 for 12 h, then the reaction was exposed to air for additional 2
h; b) Isolated yields.
Table 4. Substrates scope on alkynyl phosphonatesa)
It was generally accepted that five-membered rings also
constituted
a
broad range of potential molecules of
pharmaceutical applications. And also the methodology was
successfully developed from the same substrates but under Cu-
catalysis. Thus, a novel method for the construction of hetero-
substituted triazoles was further explored as shown in Table 3. In
the present of CuSO4·5H2O (1.0 mol%) and sodium ascorbate
(0.5 mol%), diethyl phosphonate and benzyl azides underwent
the "click reaction" in DMF at 170 oC for 12 h, offering the five-
membered 5-phosphonated 1,2,3-triazoles, as shown in Table 3,
in good yields and extremely high regioselectivity for triazoles
4a – 4e were found as the exclusive products from the system.
Under the optimal conditions, P-(2-phenylethynyl) diethyl
phosphonate (1b) cyclized with benzyl azide (2a), giving the 1-
benzyl-4-phenyl-5-diethylphosphoryl 1,2,3-triazole 4a in
excellent yield, up to 92%. In the same pattern, P-(4-tolyethynyl)
diethyl phosphonate (1n), P-(4-dimethoxyphenylethynyl) diethyl
Entry
6/7b)
6a/7a
6b/7b
6c/7c
6d/7d
6e/7e
6f/7f
Ar
R
Yield (6+7)c)
90%
1
2
3
4
5
6
7
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
Et
4-CH3C6H4
4-CH3OC6H4
4-ClC6H4
4-IC6H4
93%
86%
94%
82%
2-Naphthyl
C6H5
80%
phosphonate
phosphonate
(1o),
(1p),
P-(4-fluorophenylethynyl)
P-(4-bromophenylethynyl)
diethyl
diethyl
6g/7g
75%
phosphonate (1q) were smoothly transformed into the 5-hetero-
substituted 1,2,3-triazoles 4b – 4e in good yields, ranging from
83% to 90%. Worthy of note, the structures of 4a – 4e was
exemplified by the NOESY analysis of 4c for confirmation.[16]
a)
a)
Conditions:
Conditions: 5 (1.0 mmol), 2 (1.5 mmol), CuSO4·5H2O
(0.5mol%), sodium ascorbate (0.25 mol%) in toluene (5.0 mL) at 80 oC for 12
h; b) ratio of 6/7 was ca. 1:1 by crude 1H-NMR; c) isolated yields.
Encouraged by the results that alkynyl phosphonates were
successfully transformed into various six-membered and five-
membered hetero-cyclic compounds, the construction of sulfur-
substituted quinolines were still logically extended under the
acid-prompted system. Beyond our expectations, a novel
compound of completely different structure was isolated as
shown in scheme 2. Luckily, electron-sufficient phenyl group
including haloed phenyl groups were compatible in the system,
giving the products 8a – 8c in yields from 78% to 85%. The
products might come from the nucleophilic addition of the
alkynyl sulfides on the in-situ generated phenyl iminium ion, and
subsequent hydration reaction that happened on the remaining
C=C bond.
Table 3. Substrates scope towards triazolyl phosphonatesa)
NHPh
1) TfOH, DCE, r.t., 12 h
N3
S
Ar
SR
+
2) air, 2 h
Ar
R
O
5b, 5h, 5i
2
8a: Ar = C6H5, R = 4-CH3C6H4; 78%
8b: Ar = 4-CH3C6H4, R = C6H5; 82%
8c: Ar = 4-BrC6H4, R = C6H5; 85%
a)
Conditions: 1 (1.0 mmol), 2 (1.5 mmol), CuSO4·5H2O (0.5mol%), sodium
ascorbate (0.25 mol%) in DMF (5 mL) at 170 oC for 12 h.
Scheme 2. Reactions of alkynyl sulfides and benzyl azides
Encouraged by the good tolerance and high regioselectivity of
the "Click Reaction" of the alkynyl phosphonates, the logical
extension of the reaction towards sulfur-substituted triazoles

4
Tetrahedron
groups on the alkynyl substrates were attributed for the good
ACCEPTED MANUSCRIPT
To determine the exact structure of the isolated products, single
selectivity of the [4+2] and [3+2]-cycloaddition protocols.
crystal of 3ad, 6a and 7a, which were obtained from a mixture of
hexane and ethyl acetate (ca. 1:1 by volume), were subjected to
SO2Ph
1) 2a, TfOH, DCE, r.t., 12 h
Ar
SO2Ph
2) air, 2 h
R
N
9a - 9e
10a, R = H, 78%
10b, R = CH3, 80%
10c, R = CH3O, 85%
10d, R = Cl, 83%
10e, R = CN, 86%
XRD (X-ray diffraction) analysis. The results showed the
phosphine or sulfur-substituted aza-cyclic compounds were
successfully formed.
N
CuSO4•5H2O (5 mol%)
N
N
Ph
Ar
SO2Ph
sodium ascorbate (0.5 mol%)
tol., 80 oC, 12 h
Ar
SO2Ph
9b, 9d, 9e
11b, Ar = 4-CH3Ph, 82%
11d, Ar = 4-ClPh, 76%
11e, Ar = 4-CNPh, 72%
Figure 1. ORTEP diagram of the X-ray crystal structures of 3ad, 6a and 7a (Thermal
ellipsoids are drawn at 30% probability)
Scheme 3. Cycloaddition reactions between alkynyl sulfones and 2a
Based on the experimental results and literature explorations,[10]
possible mechanism was proposed for the [4+2]-cycloaddition
reaction towards heteroatom-substituted quinolines mediated by
triflate acid as shown in Figure 2. Firstly, rearrangement of
benzyl azide (1a), which was promoted by triflate acid, led to the
formation of N-phenyl iminium ion. Then, occurrence of
nucleophilic addition between the alkynyl phosphonates (2a) and
in-situ generated N-phenyl iminium ion, affording possible
carbocation intermediate A or B. However, formation of the
intermediate B was disfavored due the electron withdrawing
effect of the phosphonyl groups. Successively, intramolecular
electrophilic substitution step offered dihydroquinoline
(inseparable), which gave the final product phosphonate-
substituted quinolines upon the treatment of dioxygen through
oxidative aromatization step. If alkynyl sufides were used in the
protocol, electrophilic substitution might be difficult to take place,
and hydration would occurred on the carbocation intermediate,
furnishing the desired products 8 (Scheme 2).
3. Conclusion
In conclusion, a selective preparation of hetero quinolines or
triazoles, which relied on the participation of triflate acid or
CuSO4·5H2O, was disclosed. The cyclization methodology
featured for the high efficiency or good regio-selectivity. The
formation of the quinolines was attributed to the rearrangement
of the arylmethyl azides in the strong acidic system. And the
further investigation on the activities of the aza-cyclic
compounds was still in progress in our laboratory.
4. Experimental section
4.1 General remarks
All reagents were purchased from commercial companies and
used without further purification.1H and 13C NMR spectra were
recorded on a Varian INOVA-400 spectrometer in deuterated
chloroform at 25 °C with residue solvent peaks as internal
standards (δ = 7.26 ppm for 1H-NMR and δ = 77.16 ppm for 13C-
NMR). Chemical shifts (δ) are reported in ppm, and spin-spin
coupling constants (J) are given in Hz, while multiplicities are
abbreviated by s (singlet), d (doublet), t (triplet), q (quartet) and
m (multiplet). Mass spectra were recorded on a ThermoFinnigan
MAT95XP microspectrometer and High resolution mass spectra
(HRMS) were recorded on an Agilent Technologies Accurate
Mass Q-TOF 6530 microspectrometer. Infrared (IR) spectra were
reported in reciprocal centimeter (cm-1). Melting points were
recorded on a national standard melting point apparatus (Model:
Taike XT-4) and were uncorrected.
4.2 General Procedure
4.2.1 Preparations of P-(3-quinolinyl) phosphonates
A sealed tube (35 mL) equipped with a stirring bar was
charged with nitrogen for three times and then was loaded with
alkynyl phosphonate (1.0 mmol), arylmethyl azide (2.0 mmol) in
DCE (5.0 mL), then triflate acid (2.0 mmol) was added dropwise
to the solution. After addition, the tube was sealed and the
mixture was stirred at room temperature for another 12 h. Then
the reaction mixture was exposed to air or charged with air for 3
times, and then the mixture was allowed to be stirred for
additional 2 h. After the completion of the reaction (monitored by
TLC), the mixture was basified with diluted Na2CO3 (15 mL)
solution and then washed with dichloromethane (15 mL × 3). The
organic phase was combined and then concentrated. The oily
crude product was purified by column chromatography using
silica gel (200-300 mesh) as stationary phase and a mixture of
Figure 2. Proposed mechanism for the [4+2]-cycloaddition reaction
To prove our hypothesis, reactions between benzyl azide (2a) and
alkynyl sulfones 9a – 9e, which possessed C-S bonds but of
electron-withdrawing property, were conducted as shown in
Scheme 3. To our delight, [4+2]-cycloaddition reactions took
place readily with different functional groups, offering the
desired selective products 10a – 10e in good yields, from 78% to
86% in the triflate acid-mediated system. In the Cu(II)-catalysis,
alkynyl sulfones (9b, 9d and 9e) coupled with benzyl azide (2a)
in the [3+2]-cycloaddition manner, furnishing the corresponding
triazole derivatives 11d, 11d and 11e in yields ranging from 72%
to 82%. The results indicated the electron-withdrawing functional

5
o
petroleum and ethyl acetate as eluent to give the desired product
in noted yields.
White solid (309.8 mg, 78% yield ). m.p. 140 - 141 C. 1H
ACCEPTED MANUSCRIPT
NMR (400 MHz, CDCl3) δ = 9.38 (d, J = 5.1 Hz, 1H), 8.18 (d, J
= 8.5 Hz, 1H), 7.78 (t, J = 7.3 Hz, 1H), 7.47 (dd, J = 15.8, 5.6
Hz, 5H), 7.37 (d, J = 1.3 Hz, 2H), 3.94 – 3.85 (m, 2H), 3.84 –
3.74 (m, 2H), 1.56 – 1.45 (m, 4H), 1.34 – 1.24 (m, 4H), 0.87 (t, J
= 7.3 Hz, 6H) ppm. 13C NMR (100 MHz, CDCl3) δ = 154.5 (Jc-p
= 8.7 Hz), 152.4 (Jc-p = 12.8 Hz), 149.9, 136.4 (Jc-p = 5.3 Hz),
4.2.2 Preparations of triazoles derivatives
A sealed tube (35 mL) equipped with a stirring bar was loaded
with alkynyl phosphonate/sulfide (1.0 mmol), arylmethyl azides
(1.5 mmol), CuSO4·5H2O (0.5% mmol), sodium ascorbate
(0.25% mmol) in DMF (or toluene for alkynyl sulfides, 5.0 mL).
Then the mixture was stirred at 170 oC (80 oC for toluene) for 12
h. After the completion of the reaction (monitored by TLC), the
mixture was quenched with saturated NH4Cl solution (15 mL)
and then extracted with dichloromethane (15 mL × 3). The
organic phase was combined and then concentrated. The oily
crude product was purified by column chromatography using
silica gel (200-300 mesh) as stationary phase and a mixture of
hexane and ethyl acetate as eluent to give the desired product in
noted yields.
131.9, 130.2, 130.1, 129.0, 128.2, 127.9, 127.8, 121.2 (Jc-p
=
190.1 Hz), 66.4 (Jc-p = 6.4 Hz), 32.9 (Jc-p = 6.6 Hz), 19.2, 14.1
ppm. 31P NMR (160 MHz, CDCl3) δ = 15.5 ppm. IR (KBr): ν =
3477, 3060, 2961, 2875, 1688, 1607, 1560, 1480, 1375, 1257,
1164, 1026, 894, 807, 768, 699 cm-1. MS (EI): m/z (%) = 203.1
(36), 250.1 (40), 268.1 (54), 286.1 (100), 342.1 (24), 397.2 (26).
HRMS (ESI) (m/z) [C23H28NO3P+H+]: Calcd. 398.1880, Found
398.1892.
4.2.7 P-(4-Phenylquinolin-3-yl) diphenylphosphine oxide
(3ea)
4.2.3 P-(4-Phenylquinolin-3-yl) dimethylphosphonate (3aa)
1
Yellow oil (324.1 mg, 80% yield). H NMR (400 MHz,
Yellow oil (253.6 mg, 81% yield). 1H NMR (400 MHz,
CDCl3) δ = 9.35 (d, J = 5.0 Hz, 1H), 8.19 (d, J = 8.5 Hz, 1H),
7.79 (t, J = 7.0 Hz, 1H), 7.50 (dd, J = 14.7, 5.3 Hz, 5H), 7.38 –
7.33 (m, 2H), 3.56 (s, 3H), 3.53 (s, 3H) ppm. 13C NMR (100
MHz, CDCl3) δ = 154.4 (Jc-p = 8.9 Hz), 151.8 (Jc-p = 12.7 Hz),
149.6, 135.9 (Jc-p = 5.4 Hz), 131.7, 129.6, 129.5, 128.8, 127.9,
127.4 (Jc-p = 14.4 Hz), 119.8 (Jc-p = 190.4 Hz), 52.7 (Jc-p = 6.1
Hz) ppm. 31P NMR (160 MHz, CDCl3) δ = 18.1 ppm. IR (KBr):
ν = 3445, 3060, 2956, 2855, 1714, 1655, 1559, 1490, 1452, 1373,
1244, 1183, 1034, 967, 884, 832, 770, 700 cm-1. MS (EI): m/z
(%) = 203.1 (20), 217.1 (42), 250.0 (21), 280.0 (27), 312.0 (56),
313.0 (100). HRMS (EI) (m/z) [C17H16NO3P]+: Calcd.313.0862,
Found 313.0858.
CDCl3) δ = 8.83 (d, J = 5.4 Hz, 1H), 8.15 (d, J = 8.5 Hz, 1H),
7.81 – 7.75 (m, 1H), 7.59 (dd, J = 11.8, 7.8 Hz, 4H), 7.46 (d, J =
6.5 Hz, 4H), 7.36 (d, J = 7.3 Hz, 4H), 7.25 – 7.20 (m, 1H), 7.13
(t, J = 7.4 Hz, 2H), 7.05 (d, J = 7.4 Hz, 2H) ppm. 13C NMR (100
MHz, CDCl3) δ = 156.1 (Jc-p = 7.3 Hz), 152.2 (Jc-p = 14.8 Hz),
149.8, 134.9 (Jc-p = 5.0 Hz), 133.3, 132.2, 132.1, 131.0, 130.1,
129.0 (Jc-p = 12.3 Hz), 128.7, 127.9, 127.8, 127.7, 125.5 (Jc-p
=
100.6 Hz) ppm. 31P NMR (160 MHz, CDCl3) δ = 24.8 ppm. IR
(KBr): ν = 3433, 3056, 2963, 2924, 1713, 1555, 1489, 1439,
1371, 1265, 1192, 1108, 1025, 759, 698 cm-1. MS (EI): m/z (%) =
203.1 (9), 250.1 (7), 326.1 (14), 404.2 (100), 405.2 (42). HRMS
(ESI) (m/z) [C27H20NOP+H+]: Calcd. 406.1355, Found 406.1365.
4.2.8 P-[4-(p-Tolyl)quinolin-3-yl] dimethyl phosphonate
(3fa)
4.2.4 P-(4-Phenylquinolin-3-yl) diethylphosphonate (3ba)
1
Yellow oil (272.9 mg, 80% yield). 1H NMR (400 MHz,
CDCl3) δ = 9.38 (d, J = 5.1 Hz, 1H), 8.18 (d, J = 8.5 Hz, 1H),
7.79 (t, J = 7.3 Hz, 1H), 7.57 – 7.42 (m, 5H), 7.39 – 7.34 (m,
2H), 4.01 – 3.83 (m, 4H), 1.19 (t, J = 7.0 Hz, 6H) ppm. 13C NMR
(100 MHz, CDCl3) δ = 154.3 (Jc-p = 8.6 Hz), 152.1 (Jc-p = 12.9
Hz), 149.7, 136.1 (Jc-p = 5.4 Hz), 131.7, 129.9, 129.8, 128.8,
128.0, 127.6, 127.5, 120.8 (Jc-p = 189.7 Hz), 62.4 (Jc-p = 6.0 Hz),
16.4 (Jc-p = 6.6 Hz) ppm. 31P NMR (160 MHz, CDCl3) δ = 15.4
ppm. IR (KBr): ν = 3470, 3058, 2973, 2859, 1775, 1708, 1560,
1490, 1491, 1373, 1250, 1166, 1025, 966, 879, 803, 762, 699 cm-
1. MS (EI): m/z (%) = 203.1 (41), 231.1 (39), 251.1 (39), 268.1
(56), 285.1 (29), 341.1 (100). HRMS (ESI) (m/z)
[C19H20NO3P+H+]: Calcd. 342.1254, Found 342.1263.
Yellow oil, (265.0 mg, 81% yield). H NMR (400 MHz,
CDCl3) δ = 9.28 (d, J = 5.0 Hz, 1H), 8.11 (d, J = 8.5 Hz, 1H),
7.72 (t, J = 7.5 Hz, 1H), 7.48 – 7.37 (m, 2H), 7.26 (d, J = 7.7 Hz,
2H), 7.18 (d, J = 7.9 Hz, 2H), 3.51 (s, 3H), 3.48 (s, 3H), 2.40 (s,
3H) ppm. 13C NMR (100 MHz, CDCl3) δ = 154.8 (Jc-p = 9.0 Hz),
152.1 (Jc-p = 12.7 Hz), 149.7, 138.7, 133.0 (Jc-p = 5.4 Hz), 131.7,
129.8, 129.5, 128.8, 127.6, 127.5, 120.9, 119.9 (Jc-p = 189.7 Hz),
52.8 (Jc-p = 6.0 Hz), 21.7 ppm. 31P NMR (160 MHz, CDCl3) δ =
18.3 ppm. IR (KBr): ν = 3477, 3052, 2954, 2857, 1726, 1613,
1561, 1491, 1373, 1247, 1181, 1032, 892, 828, 768, 691cm-1. MS
(EI): m/z (%) = 216.0 (22), 231.1 (49), 250.0 (21), 294.0 (24),
326.1 (39), 327.1 (100). HRMS (ESI) (m/z) [C18H18NO3P+H+]:
Calcd. 328.1097, Found 328.1102.
4.2.9 P-[4-(m-Tolyl) quinolin-3-yl] dimethyl phosphonate
(3ga)
4.2.5 P-(4-Phenylquinolin-3-yl) diisopropylphosphonate (3ca)
Yellow oil (280.6 mg, 76% yield). 1H NMR (400 MHz,
CDCl3) δ = 9.42 (s, 1H), 8.15 (dd, J = 26.0, 7.8 Hz, 1H), 7.77 (t,
J = 6.9 Hz, 1H), 7.55 – 7.41 (m, 5H), 7.36 (d, J = 3.6 Hz, 2H),
4.69 – 4.56 (m, 2H), 1.21 – 1.12 (m, 12H) ppm. 13C NMR (100
MHz, CDCl3) δ = 153.7 (Jc-p = 8.1 Hz), 151.7 (Jc-p = 11.9 Hz),
149.2, 135.9(Jc-p = 5.0 Hz), 131.2, 129.9, 129.4, 128.3, 127.4,
127.3, 127.0, 121.6 (Jc-p = 180.2 Hz), 71.2 (Jc-p = 6.4 Hz), 23.8
(Jc-p = 4.5 Hz) ppm. 31P NMR (160 MHz, CDCl3) δ = 13.28 ppm.
IR (KBr): ν = 3474, 3060, 2977, 2867, 1690, 1607, 1560, 1490,
1454, 1377, 1246, 1174, 1104, 985, 890, 763, 700 cm-1. MS (EI):
m/z (%) = 203.1 (74), 250.0 (38), 268.0 (96), 285.0 (96), 369.1
(100). HRMS (ESI) (m/z) [C21H24NO3P+H+]: Calcd. 370.1567,
Found 370.1580.
1
Yellow oil (278.0 mg, 85% yield). H NMR (400 MHz,
CDCl3) δ = 9.34 (d, J = 5.0 Hz, 1H), 8.17 (d, J = 8.4 Hz, 1H),
7.78 (t, J = 7.5 Hz, 1H), 7.53 – 7.44 (m, 2H), 7.40 (t, J = 7.5 Hz,
1H), 7.31 (d, J = 7.6 Hz, 1H), 7.15 (d, J = 11.9 Hz, 2H), 3.56 (d,
J = 1.4 Hz, 3H), 3.53 (d, J = 1.4 Hz, 3H), 2.43 (s, 3H) ppm. 13C
NMR (100 MHz, CDCl3) δ = 154.8 (Jc-p = 8.9 Hz), 152.0 (Jc-p
=
12.7 Hz), 149.7, 137.7, 136.0 (Jc-p = 5.3 Hz), 131.8, 130.3, 129.8,
129.6, 128.0, 127.7, 127.5, 126.8, 119.9 (Jc-p = 190.5 Hz), 52.9
(Jc-p = 6.1 Hz), 21.7 ppm. 31P NMR (160 MHz, CDCl3) δ = 18.2
ppm. IR (KBr): ν = 3432, 3068, 2956, 2855, 1617, 1560, 1489,
1373, 1231, 1045, 833, 774 cm-1. MS (EI): m/z (%) = 217.1 (31),
231.1 (31), 264.0 (13), 294.0(11), 326.0(31), 327.1 (100). HRMS
(ESI) (m/z) [C18H18NO3P+H+]: Calcd. 328.1097, Found 328.1104.
4.2.6 P-(4-Phenylquinolin-3-yl) dibutylphosphonate (3da)
4.2.10 P-[4-(4-Methoxyphenyl) quinolin-3-yl] dimethyl
phosphonate (3ha):

6
Tetrahedron
o
Yellow solid (305.4 mg, 89% yield). m.p. 121-122 C. 1H
7.5 Hz, 1H), 7.61 – 7.54 (m, 2H), 7.52 – 7.42 (m, 3H), 3.52 (d, J
= 11.3 Hz, 3H), 3.47 (d, J = 11.3 Hz, 3H) ppm. 13C NMR (100
MHz, CDCl3) δ = 154.1 (Jc-p = 8.7 Hz), 151.7 (Jc-p = 12.8 Hz),
149.4, 133.2(Jc-p = 5.5 Hz), 132.7 (Jc-p = 41.3 Hz), 131.5, 129.5,
128.7, 128.1, 127.8, 127.3 (Jc-p = 8.4 Hz), 127.0, 126.7(Jc-p = 5.0
Hz), 119.9(Jc-p = 190.6 Hz), 52.5 (Jc-p = 6.2 Hz) ppm. 31P NMR
(160 MHz, CDCl3) δ = 18.2 ppm. IR (KBr): ν = 3440, 3054,
2954, 2852, 1724, 1560, 1496, 1370, 1249, 1180, 1033, 908, 828,
764, 693 cm-1. MS (EI): m/z (%) = 149.1 (100), 267.1 (15), 262.0
(21), 363.1 (65). HRMS (ESI) (m/z) [C21H18NO3P+H+]: Calcd.
364.1097, Found 364.1096.
ACCEPTED MANUSCRIPT
NMR (400 MHz, CDCl3) δ = 9.33 (d, J = 4.9 Hz, 1H), 8.17 (d, J
= 8.4 Hz, 1H), 7.79 (t, J = 7.5 Hz, 1H), 7.55 (d, J = 8.4 Hz, 1H),
7.47 (t, J = 7.6 Hz, 1H), 7.30 (d, J = 7.9 Hz, 2H), 7.04 (d, J = 7.9
Hz, 2H), 3.90 (s, 3H), 3.59 (s, 3H), 3.56 (s, 3H) ppm. 13C NMR
(100 MHz, CDCl3) δ = 160.4, 154.9 (Jc-p = 9.0 Hz), 152.4 (Jc-p
12.7 Hz), 150.1, 132.1, 131.3, 130.1, 127.9, 127.8, 120.5 (Jc-p
=
=
190.0 Hz), 113.8, 55.9, 53.2 (Jc-p = 6.1 Hz) ppm. 31P NMR (160
MHz, CDCl3) δ = 18.4 ppm. IR (KBr): ν = 3453, 3064, 2955,
2846, 1723, 1609, 1564, 1502, 1375, 1249, 1179, 1034, 889, 833,
771 cm-1. MS (EI): m/z (%) = 149.1 (24), 190.1 (15), 310.1 (20),
342.1 (29), 343.1 (100). HRMS (ESI) (m/z) [C18H18NO4P+H+]:
Calcd. 344.1046, Found 344.1055.
4.2.15 P-[4-(1,1'-biphenyl-4-yl) quinolin-3-yl] dimethyl
phosphonate (3ma)
4.2.11 P-[4-(3-Methoxyphenyl) quinolin-3-yl] dimethyl
phosphonate (3ia):
o
Yellow solid (323.0 mg, 83% yield). m.p. 101-102 C. 1H
NMR (400 MHz, CDCl3) δ = 9.37 (d, J = 4.9 Hz, 1H), 8.21 (d, J
= 8.5 Hz, 1H), 7.84 – 7.74 (m, 3H), 7.72 (d, J = 7.6 Hz, 2H), 7.59
(d, J = 8.4 Hz, 1H), 7.53 – 7.38 (m, 6H), 3.60 (s, 3H), 3.58 (s, 3H)
ppm. 13C NMR (100 MHz, CDCl3) δ = 154.8 (Jc-p = 8.8 Hz),
152.5 (Jc-p = 12.6 Hz), 150.3, 141.6 (Jc-p = 104.8 Hz), 135.6 (Jc-p
= 5.5 Hz), 132.4, 130.7, 130.4, 129.7, 128.5, 128.1 (Jc-p = 4.7 Hz),
127.9, 127.2, 120.6 (Jc-p = 190.5 Hz), 53.4 (Jc-p = 6.1 Hz) ppm.
31P NMR (160 MHz, CDCl3) δ = 18.1 ppm. IR (KBr): ν = 3467,
3038, 2953, 2853, 1674, 1560, 1487, 1373, 1247, 1181, 1034,
893, 832, 769, 695 cm-1. MS (EI): m/z (%) = 194.6 (7), 279.1
(19), 293.1 (33), 326.1 (21), 388.0 (43), 389.1 (100). HRMS (ESI)
(m/z) [C23H20NO3P+H+]: Calcd. 390.1254, Found 390.1260.
o
Yellow oil (281.3 mg, 82% yield). m.p. 88-89 C. 1H NMR
(400 MHz, CDCl3) δ = 9.34 (d, J = 5.0 Hz, 1H), 8.17 (d, J = 8.5
Hz, 1H), 7.79 (t, J = 7.6 Hz, 1H), 7.55 (d, J = 8.4 Hz, 1H), 7.50 –
7.39 (m, 2H), 7.04 (d, J = 8.2 Hz, 1H), 6.93 (d, J = 6.7 Hz, 2H),
3.84 (s, 3H), 3.60 – 3.52 (m, 6H) ppm. 13C NMR (100 MHz,
CDCl3) δ = 159.9, 154.8 (Jc-p = 8.9 Hz), 152.6 (Jc-p = 12.7 Hz),
150.3, 137.9 (Jc-p = 5.5 Hz), 132.4, 130.4, 129.7, 128.2,127.9 (Jc-p
= 12.8 Hz), 122.7, 120.4 (Jc-p = 190.4 Hz), 116.0, 115.2, 56.2,
53.5 (Jc-p = 11.2 Hz) ppm. 31P NMR (160 MHz, CDCl3) δ = 18.2
ppm. MS (EI): m/z(%) = 77.1 (25), 105.1 (61), 149.1 (82), 247.1
(16), 342.1(33), 343.1 (100). IR (KBr): ν = 3444, 3068, 2953,
2845, 1570, 1484, 1372, 1233, 1177, 1044, 906, 833, 772, 697
cm-1. HRMS (ESI) (m/z) [C18H18NO4P+H+]: Calcd. 344.1046,
Found 344.1052.
4.2.16
N-(2-Oxo-2-(6-methoxynaphthyl)acetyl)-S,S-
methylphenyl sulfoximine (1na)
o
1
Yellow solid (147.0 mg, 80% yield). m.p.160-161 C. H
NMR (400 MHz, CDCl3) δ = 8.53 (d, J = 16.5 Hz, 1H), 8.15 –
8.08 (m, 2H), 8.05 (dd, J = 8.6, 1.7 Hz, 1H), 7.82 (d, J = 9.0 Hz,
1H), 7.77 (d, J = 8.7 Hz, 1H), 7.72 (dd, J = 8.4, 3.0 Hz, 1H), 7.68
– 7.62 (m, 2H), 7.20 – 7.12 (m, 2H), 3.94 (s, 3H), 3.49 (s, 3H).
13C NMR (100 MHz, CDCl3) δ = 190.0, 173.8, 160.4, 138.1,
137.9, 134.5, 133.4, 131.7, 130.0, 128.2, 127.9, 127.5, 127.4,
125.3, 119.9, 106.0, 55.6, 45.0. MS(EI): m/z = 59.1 (8), 72.1 (6),
77.1 (9), 93.1 (4), 114.1 (7), 125.1 (6), 142.1 (7), 157.1 (14),
182.1 (100), 185.1 (24). IR(KBr): ν = 2921, 2849, 1672, 1479,
1446, 1387, 1327, 1266, 1225, 1173, 1092, 1027, 977.
HRMS (ESI) (m/z) [C20H17NSO4+H+]: Calcd. 368.0951, Found 3
64. 0949.
4.2.12
P-[4-(4-Chlorophenyl)
quinolin-3-yl]
dimethylphosphonate (3ja)
1
Yellow oil, (274.2 mg, 79% yield). H NMR (400 MHz,
CDCl3) δ = 9.33 (d, J = 4.9 Hz, 1H), 8.19 (d, J = 8.4 Hz, 1H),
7.81 (t, J = 7.4 Hz, 1H), 7.54 – 7.43 (m, 4H), 7.30 (d, J = 8.2 Hz,
2H), 3.61 (s, 3H), 3.58 (s, 3H) ppm. 13C NMR (100 MHz, CDCl3)
δ = 152.9 (Jc-p = 8.6 Hz), 151.5 (Jc-p = 12.5 Hz), 149.4, 134.8,
134.1 (Jc-p = 5.5 Hz), 131.7, 130.7, 129.6, 128.1, 127.5, 126.9,
119.6 (Jc-p = 190.8 Hz), 52.6 (Jc-p = 6.1 Hz) ppm. 31P NMR (160
MHz, CDCl3) δ = 17.8 ppm. IR (KBr): ν = 3474, 3056, 2955,
2854, 1724, 1560, 1486, 1374, 1255, 1182, 1029, 892, 829, 768,
677 cm-1. MS (EI): m/z (%) = 216.0 (19), 252.0 (15), 284.0 (14),
312.0 (84), 347.0 (100). HRMS (ESI) (m/z) [C17H15ClNO3P+H+]:
Calcd. 348.0551, Found 348.0553.
4.2.17
P-(6-methyl-4-phenylquinolin-3-yl)
dimethyl
phosphonate (3ab)
4.2.13 P-[4-(4-Bromophenyl) quinolin-3-yl] dimethyl
phosphonate (3ka)
1
Yellow oil (245.3 mg, 75% yield). H NMR (400 MHz,
CDCl3) δ = 9.28 (d, J = 5.0 Hz, 1H), 8.07 (d, J = 8.6 Hz, 1H),
7.63 (d, J = 8.6 Hz, 1H), 7.52 (d, J = 4.9 Hz, 3H), 7.39 – 7.32 (m,
2H), 7.21 (s, 1H), 3.55 (s, 3H), 3.52 (s, 3H), 2.40 (s, 3H) ppm.
13C NMR (100 MHz, CDCl3) δ = 153.1(Jc-p = 8.9 Hz), 150.5 (Jc-p
= 12.8 Hz), 147.8, 137.1 (Jc-p = 1.3 Hz), 135.6 (Jc-p = 5.4 Hz),
133.5, 129.0, 128.9, 128.2, 127.4, 126.8 (Jc-p = 13.0 Hz), 125.5,
119.2 (Jc-p = 190.2 Hz), 52.2 (Jc-p = 6.1 Hz), 21.4 ppm. 31P NMR
(160 MHz, CDCl3) δ = 18.4 ppm. IR (KBr): ν = 3465, 3052,
2955, 2854, 1720, 1558, 1497, 1365, 1247, 1184, 1035, 947, 833,
777, 702 cm-1. MS (EI): m/z (%) = 231.1 (6), 264.0 (4), 312.0
(16), 326.0 (39), 327.0 (100). HRMS (ESI) (m/z)
[C18H18NO3P+H+]: Calcd. 328.1097, Found 328.1108.
1
Yellow oil (320.6 mg, 82% yield). H NMR (400 MHz,
CDCl3) δ = 9.29 (d, J = 3.4 Hz, 1H), 8.13 (d, J = 8.4 Hz, 1H),
7.76 (t, J = 7.3 Hz, 1H), 7.61 (d, J = 8.1 Hz, 2H), 7.44 (q, J = 8.7
Hz, 2H), 7.20 (d, J = 8.1 Hz, 2H), 3.57 (s, 3H), 3.54 (s, 3H) ppm.
13C NMR (100 MHz, CDCl3) δ = 153.4 (Jc-p = 8.6 Hz), 152.1 (Jc-p
= 12.5 Hz), 150.0, 135.2 (Jc-p = 5.5 Hz), 132.3, 131.6, 130.2,
128.1, 127.5, 123.6, 120.2 (Jc-p = 189.9 Hz), 53.2 (Jc-p = 6.1 Hz)
ppm. 31P NMR (160 MHz, CDCl3) δ = 17.8 ppm. IR (KBr): ν =
3481, 3058, 2953, 2851, 1560, 1485, 1376, 1248, 1182, 1027,
893, 829, 768, 660 cm-1. MS (EI): m/z (%) = 156.0 (14), 217.1
(19), 280.1 (14), 312.1 (100), 319.0 (43). HRMS (ESI) (m/z)
[C17H15BrNO3P+H+]: Calcd. 392.0046, Found 392.0057.
4.2.18
P-(6-Bromo-4-phenylquinolin-3-yl)
dimethyl
4.2.14 P-[4-(Naphthalen-1-yl) quinolin-3-yl] dimethyl
phosphonate (3la)
phosphonate (3ad)
o
1
Yellow solid (289.3 mg, 74% yield). m.p. 139-140 C. H
NMR (400 MHz, CDCl3) δ = 9.35 (d, J = 4.6 Hz, 1H), 8.05 (d, J
= 8.9 Hz, 1H), 7.86 (d, J = 8.9 Hz, 1H), 7.62 (s, 1H), 7.54 (d, J =
4.5 Hz, 3H), 7.37 – 7.31 (m, 2H), 3.56 (s, 3H), 3.53 (s, 3H) ppm.
1
Yellow oil (315.9 mg, 87% yield). H NMR (400 MHz,
CDCl3) δ = 9.40 (d, J = 5.0 Hz, 1H), 8.21 (d, J = 8.5 Hz, 1H),
7.97 (dd, J = 13.4, 8.1 Hz, 2H), 7.92 – 7.86 (m, 2H), 7.80 (t, J =

7
13C NMR (100 MHz, CDCl3) δ = 153.8 (Jc-p = 9.2 Hz), 152.7 (Jc-p
= 12.6 Hz), 148.7, 135.6, 131.9 (Jc-p = 1.0 Hz), 129.9 (Jc-p = 4.5
Hz), 129.5, 128.6, 122.2 (Jc-p = 2.1 Hz), 53.3 (Jc-p = 6.1 Hz) ppm.
31P NMR (160 MHz, CDCl3) δ = 17.4 ppm. IR (KBr): ν = 3475,
3058, 2957, 2853, 1724, 1556, 1478, 1354, 1254, 1183, 1032,
920, 833, 770, 702 cm-1. MS (EI): m/z (%) = 216.0 (33), 248.0
(16), 296.9 (32), 389.9 (42), 390.9 (100). HRMS (ESI) (m/z)
[C17H15BrNO3P+H+]: Calcd. 392.0046, Found 392.0051.
NMR (160 MHz, CDCl3) δ= 7.3 ppm. IR (KBr): ν = 2984,
ACCEPTED MANUSCRIPT
2938, 2899, 1682, 1452, 1247, 1159, 1052, 1024, 975, 801, 763,
733, 700 cm-1. MS (EI): m/z (%) = 91.1 (100), 105.1 (25), 314.1
(40), 342.1 (25), 371.1 (5). HRMS (EI) (m/z)
[C19H22O3N3P]+:Calcd. 371.1404, Found 371.1393.
4.2.23 P-[1-Benzyl-5-(p-tolyl)-1H-1, 2, 3-triazol-4-yl]
diethyl phosphonate (4b)
1
Yellow oil (338.9 mg, 88% yield). H NMR (400 MHz,
4.2.19
P-(6-Cyano-4-phenylquinolin-3-yl)
dimethyl
CDCl3) δ=7.25 – 7.16 (m, 5H), 7.12 (d, J = 8.0 Hz, 2H), 7.00 (d,
J = 3.7 Hz, 2H), 5.38 (s, 2H), 4.14 – 3.98 (m, 4H), 2.36 (s, 3H),
1.17 (t, J = 7.1 Hz, 6H) ppm. 13C NMR (100 MHz, CDCl3) δ =
143.4 (Jc-p = 33.2 Hz), 140.4, 134.9, 129.8, 129.4, 128.9, 128.4,
127.6, 122.6, 62.9 (Jc-p = 5.8 Hz), 51.9, 21.5, 16.2 (Jc-p = 6.7 Hz)
ppm. 31P NMR (160 MHz, CDCl3) δ = 7.5 ppm. IR (KBr): ν
=3036, 2982, 2935, 2911, 2872, 1679, 1492, 1391, 1299, 1251,
1099, 1024, 975, 826, 800, 757, 735, 623 cm-1. MS (EI): m/z (%)
= 91.1 (100), 328.1 (20), 396.1 (15), 385.2 (4). HRMS (EI) (m/z)
[C20H24O3N3P]+: Calcd. 385.1540, Found 385.1550.
phosphonate (3ae)
o
1
Yellow solid (250.2 mg, 74% yield). m.p. 111-112 C. H
NMR (400 MHz, CDCl3) δ = 9.46 (d, J = 5.0 Hz, 1H), 8.26 (d, J
= 8.7 Hz, 1H), 7.95 – 7.85 (m, 2H), 7.57 (s, 3H), 7.34 (d, J = 4.4
Hz, 2H), 3.57 (s, 3H), 3.54 (s, 3H) ppm. 13C NMR (100 MHz,
CDCl3) δ 155.1 (Jc-p = 12.3 Hz), 150.8, 134.9 (Jc-p = 5.4 Hz),
134.4, 132.4, 131.8, 130.0, 129.8, 128.8, 127.5 (Jc-p = 13.3 Hz),
122.5 (Jc-p = 190.5 Hz), 118.8, 111.7 (Jc-p = 1.6 Hz), 53.4 (Jc-p
=
6.2 Hz) ppm. 31P NMR (160 MHz, CDCl3) δ = 16.4 ppm. IR
(neat): ν = 3456, 3065, 2958, 2857, 2230, 1719, 1558, 1492,
1366, 1256, 1179, 1036, 963, 841, 777, 702 cm-1. MS (EI): m/z
(%) = 228.0 (23), 242.0 (46), 275.0 (20), 305.0 (24), 337.0 (64),
338.0 (100). HRMS (ESI) (m/z) [C18H15BrN2O3P+H+]: Calcd.
339.0893, Found 339.0901.
4.2.24 P-[1-Benzyl-4-(2, 5-dimethoxyphenyl)-1H-1,2,3-
triazol-5-yl] diethyl phosphonate (4c)
1
Yellow oil (388.0 mg, 90% yield). H NMR (400 MHz,
CDCl3) δ = 7.17 (d, J = 4.8 Hz, 3H), 6.97 – 6.80 (m,3H), 6.85 (d,
J = 9.0 Hz, 1H), 6.59 (d, J = 2.8 Hz, 1H), 5.33 (dd, J = 110.4,
15.0 Hz, 2H), 4.20 – 4.05 (m,2H), 3.98 (dd, J = 11.8, 6.6 Hz,
2H), 3.62 (s, 3H), 3.57 (s, 3H), 1.22 (t, J = 6.9 Hz, 3H), 1.10 (t, J
= 6.9 Hz, 3H) ppm. 13C NMR (100 MHz, CDCl3) δ = 153.2,
151.0, 140.0 (Jc-p = 32.7 Hz), 137.4, 134.6, 128.5, 128.1, 127.9,
117.5, 117.0, 115.1, 112.1, 62.8 (Jc-p = 5.3 Hz), 62.5 (Jc-p = 5.6
Hz), 55.8 (Jc-p = 7.1 Hz), 52.4, 16.1 (Jc-p = 6.2 Hz) ppm. 31P NMR
(160 MHz, CDCl3) δ = 7.3 ppm. IR (KBr): ν =3060, 3036, 2975,
2934, 2872, 1667, 1596, 1468, 1451, 1387, 1240, 1165, 1105,
1025, 977, 837, 739, 700 cm-1. MS (EI): m/z (%) = 91.1 (100),
294.2 (70), 312.1 (26), 431.1 (32). HRMS (EI) (m/z)
[C21H26O5N3P]+ : Calcd. 431.1611, Found 431.1605.
4.2.20
P-(6-Nitro-4-phenylquinolin-3-yl)
dimethyl
phosphonate (3af)
o
1
Yellow solid (286.5 mg, 80% yield). m.p. 71-72 C. H
NMR (400 MHz, CDCl3) δ = 9.50 (d, J = 5.0 Hz, 1H), 8.53 (d, J
= 9.2 Hz, 1H), 8.43 (s, 1H), 8.31 (d, J = 9.2 Hz, 1H), 7.58 (d, J =
3.8 Hz, 3H), 7.38 (d, J = 4.3 Hz, 2H), 3.58 (s, 3H), 3.55 (s, 3H)
ppm. 13C NMR (100 MHz, CDCl3) δ = 156.9 (Jc-p = 9.0 Hz),
155.9 (Jc-p = 12.5 Hz), 152.1, 146.9, 135.1 (Jc-p = 5.5 Hz), 132.4,
130.4, 130.1, 129.1, 127.3 (Jc-p = 13.6 Hz), 125.6, 124.9, 122.8
(Jc-p = 191.4 Hz), 3.7 (Jc-p = 6.2 Hz) ppm. 31P NMR (160 MHz,
CDCl3) δ = 16.3 ppm. IR (KBr): ν = 3473, 3056, 2958, 2857,
1714, 1560, 1490, 1373, 1244, 1183, 1034, 884, 833, 771, 700
cm-1. MS (EI): m/z (%) = 216.0 (19), 262.0 (21), 311.0 (41),
4.2.25 P-[1-Benzyl-5-(4-fluorophenyl)-1H-1,2,3-triazol-4-
yl] diethyl phosphonate (4d)
341.0
(27),
358.0
(100).
HRMS
(ESI)
(m/z)
[C17H15BrN2O5P+H+]: Calcd. 359.0791, Found 359.0793.
1
Yellow oil (323.0 mg, 83% yield). H NMR (400 MHz,
CDCl3) δ=7.25 – 7.16 (m, 5H), 7.06 (t, J = 8.5 Hz, 2H), 7.00 –
6.91 (m, 2H), 5.38 (s, 2H), 4.15 – 3.97 (m, 4H), 1.17 (t, J = 7.1
4.2.21 P-(4-Phenylbenzo[g]quinolin-3-yl)
phosphonate (3ag)
dimethyl
Hz, 6H) ppm. 13C NMR (100 MHz, CDCl3) δ = 163.8 (Jc-p
=
o
1
Yellow solid (286.5 mg, 83% yield). m.p. 73-74 C. H
NMR (400 MHz, CDCl3) δ = 9.34 (d, J = 5.7 Hz, 1H), 7.97 (s,
2H), 7.78 (d, J = 7.9 Hz, 1H), 7.48 (d, J = 5.0 Hz, 3H), 7.40 (t, J
= 7.4 Hz, 1H), 7.33 (d, J = 4.9 Hz, 2H), 7.18 (d, J = 8.5 Hz, 1H),
7.04 (t, J = 7.9 Hz, 1H), 3.50 (s, 3H), 3.47 (s, 3H) ppm. 13C NMR
251.2 Hz), 142.3 (Jc-p = 33.1 Hz), 134.6, 132.1 (Jc-p = 8.6 Hz),
129.0, 128.7, 127.6, 116.1, 115.9, 63.1 (Jc-p = 5.9 Hz), 52.2, 16.3
(Jc-p = 6.7 Hz) ppm. 31P NMR (160 MHz, CDCl3) δ= 7.0 ppm. IR
(KBr): ν =3063, 3033, 2983, 2935, 2866, 1676, 1610, 1490,
1450, 1397, 1301, 1252, 1162, 1098, 1025, 976, 847, 800, 737
cm-1. MS (EI): m/z (%) = 91.1 (100), 332.1 (25), 380.1 (14),
389.1 (3). HRMS (EI) (m/z) [C19H21O3N3FP]+: Calcd. 389.1300,
Found 389.1299.
(100 MHz, CDCl3) δ = 153.7 (Jc-p = 10.4 Hz), 152.3, 152.0 (Jc-p
=
11.9 Hz), 140.0 (Jc-p = 5.9 Hz), 134.8, 133.9, 130.6, 129.7, 129.6,
129.4, 129.4, 128.9, 128.8, 127.6, 127.0, 124.7 (Jc-p = 12.4 Hz),
121.9 (Jc-p = 190.9 Hz), 53.2 (Jc-p = 6.2 Hz) ppm. 31P NMR (160
MHz, CDCl3) δ = 18.5 ppm. IR (KBr): ν = 3468, 3055, 2956,
2854, 1715, 1535, 1494, 1346, 1257, 1182, 1032, 835, 800, 761,
699 cm-1. MS (EI): m/z (%) = 253.1 (23), 298.1 (41), 330.1 (24),
362.1 (70) 363.1 (100). HRMS (ESI) (m/z) [C21H18N3OP+H+]:
Calcd. 364.1097, Found 364.1106.
4.2.26 P-[1-Benzyl-5-(4-bromophenyl)-1H-1, 2, 3-triazol-4-
yl] diethyl phosphonate (4e)
1
Pale yellow oil (395.2 mg, 88% yield). H NMR (400 MHz,
CDCl3) δ = 7.51 (d, J = 8.3 Hz, 2H), 7.23 (dd, J = 6.9, 2.2 Hz,
3H), 7.07 (d, J = 8.3 Hz, 2H), 7.01 – 6.94 (m, 2H), 5.38 (s, 2H),
4.15 – 4.00 (m, 4H), 1.18 (t, J = 7.1 Hz, 6H) ppm. 13C NMR (100
MHz, CDCl3) δ = 142.1 (Jc-p = 32.8 Hz), 134.6, 132.0, 131.6,
129.0, 128.8, 128.7, 127.9, 127.5, 125.0, 124.6, 63.1 (Jc-p = 5.9
Hz), 52.2, 16.3 (Jc-p = 6.6 Hz) ppm. 31P NMR (160 MHz, CDCl3)
δ = 6.8 ppm. IR (KBr): ν = 3063, 3036, 2973, 2935, 2872, 1667,
1599, 1471, 1451, 1387, 1240, 1162, 1096, 1025, 980, 834, 730,
700 cm-1. MS (EI): m/z (%) = 91.1 (100), 392.0 (11), 422.0 (7),
449.0 (2). HRMS (EI) (m/z) [C19H21O3N3BrP]+: Calcd. 449.0494,
Found 449.0498.
4.2.22 P-(1-Benzyl-5-phenyl-1H-1, 2, 3-triazol-4-yl) diethyl
phosphonate (4a)
1
Yellow oil (341.4 mg, 92% yield). H NMR (400 MHz,
CDCl3) δ = 7.47 – 7.37 (m, 3H), 7.22 (dd, J = 5.5, 3.2 Hz, 5H),
7.02 – 6.93 (m, 2H), 5.40 (s, 2H), 4.14 – 3.98 (m, 4H), 1.15 (t, J
= 7.1 Hz, 6H) ppm. 13C NMR (100 MHz, CDCl3) δ = 143.1 (Jc-p
= 33.0 Hz), 134.7, 130.2, 129.9, 128.8, 128.6, 128.4, 127.5,
125.6, 62.9 (Jc-p = 5.9 Hz), 52.0, 16.1 (Jc-p = 6.7 Hz) ppm. 31P

8
Tetrahedron
4.2.27 1-Benzyl-5-phenyl-4-(phenylthio)-1H-1, 2, 3-
= 7.8 Hz, 1H), 7.39 (dd, J = 18.3, 10.1 Hz, 3H), 7.16 – 7.04 (m,
ACCEPTED MANUSCRIPT
triazole (6a)
8H), 6.99 (dd, J = 16.0, 5.5 Hz, 3H), 5.40 (s, 2H) ppm. 13C NMR
(100 MHz, CDCl3) δ = 141.2, 136.7, 136.2, 135.2, 133.5, 132.7,
130.0, 129.0, 128.9, 128.6, 128.5, 128.4, 128.3, 127.9, 127.5,
127.5, 126.9, 126.4, 126.2, 123.2, 52.9 ppm. IR (KBr): ν = 2304,
1954, 1708, 1583, 1498, 1478, 1456, 1440, 1360, 1266, 1203,
1025, 942, 899, 822 cm-1. MS (EI): m/z (%) = 274.1 (100), 393.1
(10). HRMS (EI): m/z [C25H19N3S]+ : Calcd. 393.1300, Found
393.1302.
o
Yellow solid (154.4 mg, 45% yield). m.p. 115-117 C.1H
NMR (400 MHz, CDCl3) δ = 7.44 – 7.41 (m, 1H), 7.39 – 7.35
(m, 2H), 7.30 – 7.26 (m, 3H), 7.21 – 7.16 (m, 4H), 7.15 – 7.10
(m, 3H), 7.09 – 7.03 (m, 2H), 5.50 (s, 2H) ppm. 13C NMR (100
MHz, CDCl3) δ = 141.6, 136.9, 136.6, 135.5, 130.4, 130.2, 129.5,
129.4, 129.3, 128.9, 127.9, 126.8, 126.5, 53.3 ppm. IR (KBr): ν =
2924, 2854, 1460, 1377, 722 cm-1. MS (EI): m/z (%) = 224.1
(100), 343.1 (18). HRMS (EI): m/z [C21H17N3S]+: Calcd.
343.1138, Found 343.1140.
4.2.33
1-Benzyl-4-(ethylthio)-5-phenyl-1H-1,2,3-triazole
(6g)
1
4.2.28 1-Benzyl-4-(phenylthio)-5-(p-tolyl)-1H-1, 2, 3-
triazole (6b)
Yellow oil (109.2 mg, 37% yield). H NMR (400 MHz,
CDCl3) δ = 7.47 – 7.40 (m, 3H), 7.29 – 7.18 (m, 5H), 7.10 – 6.96
(m, 2H), 5.46 (s, 2H), 2.95 – 2.87 (m,2H), 1.22 (t, J = 7.4 Hz,
3H)ppm. 13C NMR (100 MHz, CDCl3) δ = 138.1, 135.2, 129.6,
128.8, 128.8, 128.2, 127.3, 126.4, 52.5, 28.9, 15.0 ppm. IR
(KBr): ν = 1731, 1541, 1391, 856, 811, 734, 692 cm-1. MS (EI):
m/z (%) = 91(100), 176 (100), 295.1 (20). HRMS (EI):
m/z[C17H17N3S]+: Calcd. 295.1138, Found 295.1130.
o
1
Yellow solid (164.3 mg, 46% yield). m.p. 98-99 C. H
NMR (400 MHz, CDCl3) δ = 7.16 (s, 3H), 7.12 – 6.94 (m, 9H),
6.91 (d, J = 7.7 Hz, 2H), 5.38 (s, 2H), 2.26 (s, 3H) ppm. 13C
NMR (100 MHz, CDCl3) δ = 141.9, 140.7, 136.9, 136.7, 135.7,
130.09, 130.07, 129.5, 129.4, 128.9, 128.7, 127.9, 126.8, 123.4,
53.3, 22.0 ppm. IR (KBr): ν = 3052, 2924, 2854, 2305, 1951,
1911, 1709, 1583, 1265, 1049, 1025, 826, 737 cm-1. MS (EI): m/z
(%) = 238.1 (100), 357.1 (15). HRMS (EI): m/z [C22H19N3S]+ :
Calcd. 357.1300, Found 357.1303.
4.2.34 1-Benzyl-4-phenyl-5-(phenylthio)-1H-1, 2, 3-triazole
(7a)
o
1
Yellow solid (154.4 mg, 45% yield). m.p. 84-87 C. H
NMR (400 MHz, CDCl3) δ = 8.11 – 8.06 (m, 2H), 7.42 – 7.34
(m, 3H), 7.25 – 7.20 (m, 5H), 7.17 – 7.09 (m, 3H), 6.93 – 6.82
(m, 2H), 5.59 (s, 2H) ppm. 13C NMR (100 MHz, CDCl3) δ =
151.7, 135.4, 134.5, 131.1, 130.4, 129.7, 129.6, 129.5, 129.2,
129.0, 128.0, 127.6, 127.4, 123.3, 53.3 ppm. IR (KBr): ν = 3062,
3033, 2928, 1959, 1887, 1581, 1478, 1440, 1343, 1219, 1073,
989, 917, 733, 693 cm-1. MS (EI): m/z (%) = 91.0 (68), 224.1
(100), 343.1 (18). HRMS (EI): m/z [C21H17N3S]+:
Calcd.343.1138, Found 343.1132.
4.2.29 1-Benzyl-5-(4-methoxyphenyl)-4-(phenylthio)-1H-1,
2, 3-triazole (6c)
1
Colorless oil (156.7 mg, 42% yield). H NMR (400 MHz,
CDCl3) δ = 7.28 (t, J = 6.6 Hz, 3H), 7.23 – 6.99 (m, 9H), 6.89 (d,
J = 8.5 Hz, 2H), 5.48 (s, 2H), 3.82 (s, 3H) ppm. 13C NMR (100
MHz, CDCl3) δ = 160.6, 141.1, 136.3, 136.0, 135.1, 130.9, 128.9,
128.8, 128.2, 128.0, 127.2, 126.1, 117.7, 114.2, 55.3, 52.6 ppm.
IR (KBr): ν = 2937, 2837, 2551, 2046, 1613, 1581, 1489, 1255,
1178, 1031, 837, 615 cm-1. MS (EI): m/z (%) = 254.1 (100),
373.1 (12). HRMS (EI): m/z [C22H19N3OS]+: Calcd. 373.1249,
Found 373.1250.
4.2.35 1-Benzyl-5-(phenylthio)-4-(p-tolyl)-1H-1, 2, 3-
triazole (7b)
o
1
4.2.30
1,2,3-triazole (6d)
1-Benzyl-5-(4-chlorophenyl)-4-(phenylthio)-1H-
Yellow solid (167.9 mg, 47% yield). m.p. 67-69 C. H
NMR (400 MHz, CDCl3) δ = 7.88 (d, J = 7.8 Hz, 2H), 7.15 –
7.08 (m, 7H), 7.01 (d, J = 6.5 Hz, 3H), 6.76 (d, J = 7.2 Hz, 2H),
5.46 (s, 2H), 2.24 (s, 3H) ppm. 13C NMR (100 MHz, CDCl3) δ =
151.5, 139.2, 135.1, 134.2, 129.99, 129.86, 129.2, 128.8, 128.6,
127.8, 127.5, 127.1, 127.0, 122.5, 52.9, 21.9 ppm. IR (KBr): ν =
2732, 2683, 2605, 2411, 2305, 2159, 1950, 1910, 1731, 1543,
1025, 991 cm-1. MS (EI): m/z (%) = 238.1 (100), 357.1 (17).
HRMS (EI): m/z [C22H19N3S]+: Calcd. 357.1300, Found
357.1305.
1
Yellow oil (177.2 mg, 47% yield). H NMR (400 MHz,
CDCl3) δ = 7.24 (d, J = 8.2 Hz, 2H), 7.20 – 7.15 (m, 3H), 7.12 –
7.02 (m, 5H), 6.93 (d, J = 8.2 Hz, 4H), 5.38 (s, 2H) ppm. 13C
NMR (100 MHz, CDCl3) δ = 140.2, 137.1, 136.5, 136.1, 135.1,
131.3, 129.4, 129.3, 129.2, 128.8, 128.7, 127.6, 126.8, 124.6,
53.2 ppm. IR (KBr): ν = 3053, 2926, 2854, 2685, 2305, 1708,
1605, 1583, 1477, 1265, 1094, 1023, 1002, 896, 836, 739 cm-1.
MS (EI): m/z (%) = 258.1 (100), 348.1 (16), 377.1 (16) [M+].
HRMS (EI): m/z [C21H16ClN3S]+ : Calcd. 377.0748, Found
377.0742.
4.2.36 1-Benzyl-4-(4-methoxyphenyl)-5-(phenylthio)-1H-1,
2, 3-triazole (7c)
o
1
4.2.31 1-Benzyl-5-(4-iodophenyl)-4-(phenylthio)-1H-1,2,3-
triazole (6e)
Yellow solid (164.2 mg, 44% yield). m.p. 93-95 C. H
NMR (400 MHz, CDCl3) δ = 8.03 (d, J = 8.3 Hz, 2H), 7.22 (s,
5H), 7.12 (d, J = 6.5 Hz, 3H), 6.89 (dd, J = 21.8, 7.7 Hz, 4H),
5.57 (s, 2H), 3.80 (s, 3H) ppm. 13C NMR (100 MHz, CDCl3) δ =
159.9, 150.7, 134.5, 133.6, 129.4, 128.6, 128.3, 128.1, 128.0,
126.5, 126.3, 122.6, 121.3, 113.9, 55.2, 52.2 ppm. IR (KBr): ν =
3061, 2938, 2837, 2054, 1955, 1891, 1725, 1613, 1579, 1177,
1031, 990 cm-1. MS (EI): m/z (%) = 254.1 (100), 373.1 (12).
HRMS (EI): m/z [C22H19N3OS]+ : Calcd. 373.1249, Found
373.1248.
o
Yellow solid (187.6 mg, 40% yield). m.p. 131-134 C. 1H
NMR (400 MHz, CDCl3) δ = 7.71 (d, J = 8.4 Hz, 2H), 7.36 –
7.27 (m, 3H), 7.24 – 7.01 (m, 7H), 6.82 (d, J = 8.4 Hz, 2H), 5.48
(s, 2H) ppm. 13C NMR (100 MHz, CDCl3) δ = 140.1, 138.0,
136.7, 135.8, 134.8, 131.2, 129.0, 129.0, 128.5, 128.4, 127.3,
126.5, 125.4, 96.5, 52.9 ppm. IR (KBr): ν = 2305, 1951, 1907,
1709, 896, 830, 549 cm-1. MS (EI): m/z (%) = 238.0 (100), 469.0
(12) [M+]. HRMS (EI): m/z [C21H16IN3S]+ : Calcd. 469.0104,
Found 469.0095.
4.2.37 1-Benzyl-4-(4-chlorophenyl)-5-(phenylthio)-1H-1, 2,
3-triazole (7d)
4.2.32
1-Benzyl-5-(naphthalen-2-yl)-4-(phenylthio)-1H-
o
1
1,2,3-triazole (6f)
Yellow solid (177.2 mg, 43% yield). m.p. 89-91 C. H
NMR (400 MHz, CDCl3) δ = 7.92 (d, J = 8.3 Hz, 2H), 7.22 (d, J
= 8.4 Hz, 2H), 7.08 (s, 5H), 6.99 (s, 3H), 6.76 – 6.69 (m, 2H),
o
1
White solid (157.3 mg, 40% yield). m.p. 113-115 C. H
NMR (400 MHz, CDCl3) δ = 7.71 (t, J = 6.9 Hz, 2H), 7.55 (d, J

9
5.45 (s, 2H) ppm. 13C NMR (100 MHz, CDCl3) δ = 149.5, 134.6,
134.3, 133.1, 129.5, 128.8, 128.63, 128.58, 128.3, 128.2, 128.0,
126.7, 126.4, 122.6, 52.3 ppm. IR (KBr): ν = 2924, 2854, 1968,
1922, 1580, 989, 839, 741 cm-1. MS (EI): m/z (%) = 91.0 (100),
258.1 (77), 377.1 (18). HRMS (EI): m/z[C21H16ClN3S]+: Calcd.
377.0748, Found 377.0739.
4.98 (s, 1H), 4.49 – 4.33 (m, 2H), 2.32 (s, 3H) ppm. 13C NMR
ACCEPTED MANUSCRIPT
(100 MHz, CDCl3) δ = 169.8, 138.8, 138.2, 135.1, 133.6, 130.4,
130.2, 129.8, 129.2, 128.6, 128.2, 128.0, 127.8, 57.6, 44.5, 21.7
ppm. IR (KBr): ν = 3673, 3339, 3021, 2312, 1664, 1506, 1174,
752, 694 cm-1. MS (EI): m/z (%) = 91.1 (42), 105.1 (21), 213.1
(100), 214.1 (63), 247.2 (14). HRMS (ESI) (m/z)
[C22H21NOS+H+]: Calcd. 348.1417, Found 348.1426.
4.2.38 1-Benzyl-4-(4-iodophenyl)-5-(phenylthio)-1H-1, 2, 3-
triazole (7e)
4.2.44 1-(4-Bromophenyl)-3-(phenylamino)-2-(phenylthio)
propan-1-one (8c)
o
1
Yellow solid (197.0 mg, 42% yield). m.p. 91-93 C. H
NMR (400 MHz, CDCl3) δ = 7.87 – 7.79 (m, 2H), 7.73 – 7.69
(m, 2H), 7.22 (d, J = 2.3 Hz, 5H), 7.16 – 7.12 (m, 3H), 6.86 –
6.80 (m, 2H), 5.58 (s, 2H) ppm. 13C NMR (100 MHz, CDCl3) δ =
150.7, 138.7, 135.2, 134.0, 130.5, 129.7, 129.5, 129.3, 129.0,
128.4, 127.7, 127.4, 123.6, 95.8, 53.4 ppm. IR (KBr): ν = 3029,
2933, 1580, 1495, 1388, 1335, 1265, 1226, 1134, 1025, 988, 831
cm-1. MS (EI): m/z (%) = 287.0 (100), 302 (53),469.0 (20).
HRMS (EI): m/z[C21H16IN3S]+: Calcd. 469.0104, Found
469.0095.
Off-white solid (349.4 mg, 85% yield). m.p. 170-172 oC. 1H
NMR (400 MHz, CDCl3) δ = 7.46 (d, J = 8.2 Hz, 2H), 7.31 –
7.24 (m, 10H), 7.07 (d, J = 2.9 Hz, 3H), 4.93 (s, 1H), 4.50 – 4.36
(m, 2H) ppm. 13C NMR (100 MHz, CDCl3) δ = 168.3, 137.2,
134.9, 133.4, 131.7, 130.1, 129.6, 129.1, 128.4, 127.39, 127.37,
127.3, 122.1, 56.6, 43.7 ppm. IR (KBr): ν = 3308, 2934, 1656,
1509, 1236, 910, 782, 741, 690 cm-1. MS (EI): m/z (%) = 77.1
(81), 91.1 (61), 105.1 (94), 197.1 (36), 279.0 (100), 411.0 (12).
HRMS (ESI) (m/z) [C22H18BrNOS+H+]: Calcd. 412.0365, Found
412.0334.
4.2.39
1-Benzyl-4-(naphthalen-2-yl)-5-(phenylthio)-1H-
1,2,3-triazole (7f)
4.2.45 4-Phenyl-3-(phenylsulfonyl)quinoline (10a)
o
1
1
Yellow solid (157.3 mg, 40% yield). m.p. 98-100 C. H
NMR (400 MHz, CDCl3) δ = 8.47 (s, 6H), 8.47 (s, 6H), 8.15 (d, J
= 8.6 Hz, 6H), 8.15 (d, J = 8.6 Hz, 6H), 7.84 – 7.64 (m, 20H),
7.79 – 7.70 (m, 18H), 7.40 – 7.34 (m, 12H), 7.52 – 7.33 (m,
14H), 7.16 (d, J = 5.6 Hz, 44H), 7.16 (d, J = 5.6 Hz, 30H), 7.03
(d, J = 6.7 Hz, 18H), 7.03 (d, J = 6.7 Hz, 16H), 6.83 (d, J = 7.4
Hz, 13H), 6.83 (d, J = 7.4 Hz, 12H), 5.54 (s, 12H), 5.54 (s, 12H)
ppm. 13C NMR (100 MHz, CDCl3) δ = 150.9, 134.8, 133.8,
133.6, 133.5, 129.8, 129.0, 128.8, 128.6, 128.5, 128.4, 127.9,
127.8, 127.0, 126.74, 126.71, 126.5, 124.9, 123.1, 52.7 ppm. IR
(KBr): ν = 1957, 1876, 1716, 942, 901, 633 cm-1. MS (EI): m/z
(%) = 274.1 (100), 393.1 (22). HRMS (EI): m/z [C25H19N3S]+ :
Calcd. 393.1300, Found 393.1306.
Yellowish oil (129.4 mg, 75% yield). H NMR (400 MHz,
CDCl3) δ = 9.84 (s, 1H), 8.24 (d, J = 8.5 Hz, 1H), 7.85 (t, J = 7.6
Hz, 1H), 7.48 (t, J = 7.3 Hz, 3H), 7.32 (dd, J = 25.4, 7.2 Hz, 7H),
6.96 (d, J = 7.4 Hz, 2H) ppm. 13C NMR (100 MHz, CDCl3) δ =
149.9, 149.7, 147.6, 140.8, 132.9, 132.4, 132.3, 132.2, 129.9,
129.58, 128.59, 128.5, 127.79, 127.75, 127.6, 127.4, 127.3 ppm.
IR (KBr): ν = 3471, 3075, 2935, 1605, 1560, 1495, 1459, 1313,
1144, 1083, 1034, 728 cm-1. MS (EI): m/z (%) = 176.0 (22),
203.0 (27), 250.0 (10), 345.0 (100). HRMS (EI) (m/z)
[C21H15NO2S]+: Calcd. 345.0842, Found 345.0823.
4.2.46 4-(p-Tolyl)-3-(phenylsulfonyl)quinoline (10b)
1
Yellowish oil (143.6 mg, 80% yield). H NMR (400 MHz,
CDCl3) δ = 9.82 (s, 1H), 8.23 (d, J = 8.5 Hz, 1H), 7.84 (t, J = 7.6
Hz, 1H), 7.48 (t, J = 7.5 Hz, 2H), 7.42 – 7.35 (m, 3H), 7.29 (d, J
= 7.4 Hz, 2H), 7.15 (d, J = 7.6 Hz, 2H), 6.85 (d, J = 7.6 Hz, 2H),
2.49 (s, 3H) ppm. 13C NMR (100 MHz, CDCl3) δ = 150.6, 150.0,
148.0, 141.2, 138.9, 133.2, 132.8, 132.5, 130.2, 129.9, 129.8,
128.8, 128.6, 128.1, 128.0, 127.9, 127.8, 21.7 ppm. IR (KBr): ν =
3461, 3065, 2925, 1625, 1551, 1485, 1437, 1306, 1070, 863, 768
cm-1. MS (EI): m/z (%) = 119.0 (23), 217.0 (28), 249.0 (21),
359.0 (100). HRMS (EI) (m/z) [C22H17NO2S]+: Calcd. 359.0882,
Found 359.0883.
4.2.41
1-Benzyl-5-(ethylthio)-4-phenyl-1H-1,2,3-triazole
(7g)
1
Yellow oil (112.1 mg, 38% yield). H NMR (400 MHz,
CDCl3) δ = 8.23 – 8.13 (m, 2H), 7.47 – 7.42 (m, 2H), 7.38 –
7.28 (m, 6H), 5.69 (s, 2H), 2.44 – 2.38 (m,2H), 0.95 (t, J = 7.4
Hz, 3H) ppm. 13C NMR (100 MHz, CDCl3) δ = 149.4, 135.6,
131.0, 129.1, 128.8, 128.7, 128.6, 128.1, 127.1, 125.7, 52.3, 30.3,
14.7 ppm. IR (KBr): ν = 1629, 1388, 1210, 911, 854, 736 cm-1.
MS (EI): m/z (%) = 238.1 (38), 295.1 (19) [M+]. HRMS (EI): m/z
[C17H17N3S]+:295.1138, Found 295.1131.
4.2.47 4-(p-Methoxyphenyl)-3-(phenylsulfonyl) quinoline
(10c)
4.2.42 1-Phenyl-3-(phenylamino)-2-(p-tolylthio) propan-1-
one (8a)
Yellowish solid (159.4 mg, 85% yield). m.p. 123-125 oC. 1H
NMR (400 MHz, CDCl3) δ = 9.67 (s, 1H), 8.09 (d, J = 8.5 Hz,
1H), 7.70 (t, J = 7.7 Hz, 1H), 7.39 – 7.27 (m, 3H), 7.25 – 7.09
(m, 5H), 6.73 (s, 3H), 3.78 (s, 3H). 13C NMR (100 MHz, CDCl3)
δ = 159.0, 149.2, 148.8, 146.7, 139.9, 132.0, 131.8, 131.2, 130.4,
128.7, 127.6, 126.9, 126.8, 126.4, 123.5, 112.2, 52.4 ppm. IR
(KBr): ν = 3443, 3045, 2926, 1635, 1545, 1475, 1438, 1310, 853,
748 cm-1. MS (EI): m/z (%) = 135.0 (34), 191.0 (10), 267.0 (6),
375.0 (100). HRMS (EI) (m/z) [C22H17NO3S]+: Calcd. 375.0928,
Found 375.0925.
Off-white solid (270.8 mg, 78% yield). m.p. 140-142 oC. 1H
NMR (400 MHz, CDCl3) δ = 7.34 (d, J = 7.4 Hz, 2H), 7.28 –
7.21 (m, 3H), 7.19 – 7.12 (m, 5H), 6.99 (d, J = 7.8 Hz, 5H), 4.88
(s, 1H), 4.40 (dd, J = 14.8, 6.1 Hz, 1H), 4.31 (dd, J = 14.8, 5.4
Hz, 1H), 2.25 (s, 3H) ppm. 13C NMR (100 MHz, CDCl3) δ =
169.2, 137.7, 137.7, 136.3, 130.8, 130.5, 130.0, 128.9, 128.6,
128.3, 128.2, 127.7, 127.5, 58.0, 44.0, 21.1ppm. IR (KBr): ν =
3658, 3285, 3028, 1655, 1521, 1019, 806, 740, 695cm-1. MS (EI):
m/z (%) = 91.1 (42), 213.1 (100), 214.1 (81), 247.2 (26). HRMS
(ESI) (m/z) [C22H21NOS+H+]: Calcd. 348.1417, Found 348.1426.
4.2.48 4-(p-Chlorophenyl)-3-(phenylsulfonyl) quinoline
(10d)
Yellowish solid (157.3 mg, 83% yield). m.p. 148-150 oC. 1H
NMR (400 MHz, CDCl3) δ = 9.78 (s, 1H), 8.22 (d, J = 8.5 Hz,
1H), 7.84 (t, J = 7.7 Hz, 1H), 7.48 (t, J = 7.6 Hz, 2H), 7.39 – 7.28
(m, 7H), 6.88 (d, J = 8.1 Hz, 2H) ppm. 13C NMR (100 MHz,
4.2.43 3-(Phenylamino)-2-(phenylthio)-1-(p-tolyl) propan-1-
one (8b)
Off-white solid (284.6 mg, 82% yield). m.p. 142-144 oC. 1H
NMR (400 MHz, CDCl3) δ = 7.29 (d, J = 7.2 Hz, 4H), 7.24 (d, J
= 6.7 Hz, 6H), 7.13 (d, J = 7.7 Hz, 2H), 7.05 (d, J = 2.6 Hz, 3H),

10
Tetrahedron
ACCEPTED MANUSCRIPT
CDCl3) δ = 150.4, 149.1, 148.2, 141.3, 135.6, 133.8, 133.1,
Science and Technology Department Program (grant number
133.0, 131.9, 131.5, 130.4, 129.3, 128.7, 128.6, 128.3, 127.7,
127.6 ppm. IR (KBr): ν = 3471, 3075, 2935, 1606, 1560, 1494,
1447, 1371, 1314, 728 cm-1. MS (EI): m/z (%) = 179.0 (22),
203.0 (11), 314.0 (20), 379.0 (100). HRMS (EI) (m/z)
[C22H17NO2S]+: Calcd. 379.3404, Found 379.3406.
2011WK4007, 06FJ4115) and The Fundamental Research Funds
for the Central Universities, Hunan University (grant number
531107040840).
Supplementary Material
4.2.49 4-(p-Cyanophenyl)-3-(phenylsulfonyl) quinoline (10e)
Supplementary data related to this article can be found at
http://dx.doi.org/10.1016/j.tet.xx.
Yellowish solid (159.1 mg, 86% yield). m.p. 108-110 oC. 1H
NMR (400 MHz, CDCl3) δ = 9.78 (s, 1H), 8.26 (d, J = 8.5 Hz,
1H), 7.87 (t, J = 7.6 Hz, 1H), 7.65 (d, J = 8.0 Hz, 2H), 7.52 (m,
2H), 7.36 (m, 4H), 7.20 (d, J = 8.5 Hz, 1H), 7.11 (d, J = 8.1 Hz,
2H) ppm. 13C NMR (100 MHz, CDCl3) δ = 150.4, 148.2, 147.9,
146.4, 141.3, 141.1, 138.2, 136.0, 134.1, 133.2, 132.7, 132.0,
131.4, 130.6, 129.5, 129.1, 128.3, 127.2, 126.4, 118.7, 113.4
ppm. IR (KBr): ν = 3443, 3065, 2875, 1634, 1547, 1505, 1436,
1380, 1310, 748 cm-1. MS (EI): m/z (%) = 175.0 (9), 217.0 (22),
305.0 (22), 370.0 (100). HRMS (EI) (m/z) [C22H14N2O2S]+:
Calcd. 370.0774, Found 370.0776.
References
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4.2.50
1-Benzyl-5-(phenylsulfonyl)-4-(p-tolyl)-1H-1,2,3-
triazole (11b)
Yellowish solid (159.5 mg, 82% yield). m.p. 101-103 oC. 1H
NMR (400 MHz, CDCl3) δ = 7.85 (d, J = 7.8 Hz, 2H), 7.58 (t, J
= 7.4 Hz, 1H), 7.46 (t, J = 7.6 Hz, 2H), 7.28 (t, J = 6.5 Hz, 5H),
7.06 (d, J = 7.8 Hz, 2H), 7.00 (d, J = 6.9 Hz, 2H), 5.35 (s, 2H),
2.47 (s, 3H) ppm. 13C NMR (100 MHz, CDCl3) δ = 145.8, 141.3,
141.0, 139.6, 134.2, 133.9, 130.2, 129.7, 129.3, 129.1, 128.9,
128.2, 128.0, 121.3, 52.7, 21.8 ppm. IR (KBr): ν = 3052, 2924,
1951, 1911, 1709, 1583, 1265, 826, 737 cm-1. MS (EI): m/z (%) =
91.0 (100), 221.0 (23), 298.0 (21), 389.0 (18). HRMS (EI) (m/z)
[C22H19N3O2S]+: Calcd. 389.1197, Found 389.1196.
2. Bravo-Altamirano K, Huang Z, Montchamp JL, Tetrahedron 2005;61:
6315-6329;
3. Lee SJ, Kim HS, Yang HW, Yoo BW, Yoon CM, Bull. Korean Chem. Soc.
2014;35: 2155-2158;
4. Wang YF, Toh KK, Lee JY, Chiba S, Angew. Chem. Int. Ed.
2011;50:5927-5931;
5. Xiang CB, Bian YJ, Mao XR, Huang ZZ, J. Org. Chem. 2012;77:7706-
7710;
6. Li Y, Das S, Zhou S, Junge K, Beller M, J. Am. Chem. Soc.
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7. Zhao YL, Wu GJ, Han FS, Chem. Commun. 2012;48:5868-5870;
8. Richter H, Garcia Mancheno O, Org. Lett. 2011;13:6066-6069;
9. Zhao YL, Wu GJ, Li Y, Gao LX, Han FS, Chem. Eur. J. 2012;18:9622-
9627;
10. Tummatorn J, Poonsilp P, Nimnual P, Janprasit J, Thongsornkleeb C,
Ruchirawat S, J. Org. Chem. 2015; 80:4516-4525;
11.a) Su Q, Yan H, Gao SC, Xie DX, Cai QY, Shao G, Peng ZH, An DL,
Synth. Commun. 2013;43:2648-2655;
b) Zhang Y, Zhang YQ, Xiao J, Peng ZH, Dong WR, An DL, Eur. J. Org.
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4.2.51 1-Benzyl-5-(phenylsulfonyl)-4-(4-chlorophenyl)-1H-
1,2,3-triazole (11d)
o
1
White solid (155.4 mg, 76% yield). m.p. 113-115 C. H
NMR (400 MHz, CDCl3) δ = 7.71 (d, J = 7.0 Hz, 2H), 7.52 (d, J
= 6.1 Hz, 1H), 7.37 (m, 4H), 7.18 (d, J = 4.9 Hz, 3H), 7.02 (dd, J
= 4.1, 2.5 Hz, 2H), 6.87 (s, 2H), 5.29 (d, J = 3.8 Hz, 2H) ppm.
13C NMR (100 MHz, CDCl3) δ = 170.4, 140.1, 137.7, 136.7,
133.6, 133.4, 131.1, 128.9, 128.72, 128.6, 128.4, 127.5, 127.3,
122.3, 52.4 ppm. IR (KBr): ν = 2924, 2854, 1968, 1922, 1580,
989, 839, 741 cm-1. MS (EI): m/z (%) = 91.0 (100), 139.0 (24),
240.0 (25), 317.0 (23), 375.0 (30), 409.0 (14). HRMS (EI) (m/z)
[C21H16ClN3O2S]+: Calcd. 409.0650, Found 409.0652.
4.2.52 1-Benzyl-5-(phenylsulfonyl)-4-(4-cyanophenyl)-1H-
1,2,3-triazole (11e)
Yellowish solid (152.1 mg, 72% yield). m.p. 121-123 oC.1H
NMR (400 MHz, CDCl3) δ = 7.78 (d, J = 7.8 Hz, 2H), 7.67 (d, J
= 8.0 Hz, 2H), 7.55 (t, J = 7.4 Hz, 1H), 7.43 (t, J = 7.6 Hz, 2H),
7.24 – 7.15 (m, 5H), 6.85 (d, J = 7.3 Hz, 2H), 5.32 (s, 2H) ppm.
13C NMR (100 MHz, CDCl3) δ = 171.0, 146.5, 140.4, 137.3,
134.3, 133.6, 132.5, 131.2, 129.5, 129.3, 129.2, 128.2, 127.8,
117.9, 114.9, 53.33 ppm. IR (KBr): ν = 2305, 1951, 1907, 1709,
896, 830, 734 cm-1. MS (EI): m/z (%) = 91.0 (100), 231.0 (35),
307.0 (25), 336.1 (22), 400.0 (5). HRMS (EI) (m/z)
[C22H16N4O2S]+: Calcd. 400.0993, Found 400.0991.
12. For reviews, see: Tiwari VK, Mishra BB, Mishra KB, Mishra N, Singh
AS, Chen X, Chem. Rev. 2016;116:3086-3240 and the citations therein;
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15. For more details, see CCDC 1519981, 911337 and 911338.
16. For more information, see supporting file.
Acknowledgments
The authors are grateful for the financial support from the
National Natural Science Foundation of China (NSFC) (grant
number 21072052), the National Basic Research Program of
China (grant number 2009CB421601), and the Hunan Provincial
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