Synthesis of 2(5H)-furanone derivatives with Bis-1,2,3-triazole structure

Article abstract of DOI:10.1002/cjoc.201200638

A series of new chiral 2(5H)-furanone derivatives containing bis-1,2,3-triazole moiety were designed and synthesized from (5S)-5-alkoxy-3,4-dihalo-2(5H)-furanones 1, dicarboxyl amino acids 2, propargyl bromide, and organic azides 5 under mild conditions via the sequential three steps, including asymmetric Michael addition-elimination, substitution and no-ligand click reaction. Twelve new intermediates, including N-[5-alkoxy-2(5H)-furanonyl] dicarboxyl amino acids 3 and their corresponding propargyl esters 4, and twelve target molecules 6 were characterized by FTIR, ¹H NMR, ¹³C NMR, MS and elemental analysis. The influences of different synthetic conditions and substrates in each step were investigated. The research provides a new method and idea for the synthesis of 2(5H)-furanone compounds with polyheterocyclic structure due to the diversities of four basic unit molecules. A series of new chiral 2(5H)-furanone derivatives containing bis-1,2,3-triazole moiety are designed and synthesized from 4 basic unit molecules under mild conditions via the sequential three steps, including asymmetric Michael addition-elimination, substitution and no-ligand click reaction. Copyright

Full text of DOI:10.1002/cjoc.201200638

FULL PAPER
DOI: 10.1002/cjoc.201200638
Synthesis of 2(5H)-Furanone Derivatives with
Bis-1,2,3-triazole Structure
Huo, Jingpei(霍景沛)
LÜ, Meixiang(吕梅香)
Li, Yizhong(李意忠)
Wang, Zhaoyang*(汪朝阳)
School of Chemistry and Environment, South China Normal University, Guangzhou, Guangdong 510006, China
A series of new chiral 2(5H)-furanone derivatives containing bis-1,2,3-triazole moiety were designed and syn-
thesized from (5S)-5-alkoxy-3,4-dihalo-2(5H)-furanones 1, dicarboxyl amino acids 2, propargyl bromide, and or-
ganic azides 5 under mild conditions via the sequential three steps, including asymmetric Michael addi-
tion-elimination, substitution and no-ligand click reaction. Twelve new intermediates, including N-[5-alkoxy-
2(5H)-furanonyl] dicarboxyl amino acids 3 and their corresponding propargyl esters 4, and twelve target molecules
1
6 were characterized by FTIR, H NMR, 13C NMR, MS and elemental analysis. The influences of different syn-
thetic conditions and substrates in each step were investigated. The research provides a new method and idea for the
synthesis of 2(5H)-furanone compounds with polyheterocyclic structure due to the diversities of four basic unit
molecules.
Keywords 2(5H)-furanone, bis-1,2,3-triazole, amino acids, synthetic methods, click chemistry
Introduction
amino acids as new building blocks.
Because 1,2,3-triazole compounds have good bio-
logical activities, including antifungal,[1] antibacterial,[2]
antitubercular,[3] anti-cancer,[4] anti-virus,[5] anti-inflam-
matory,[6] and so on, more and more importance has
been attached to the 1,2,3-triazole drugs, especially bis-
1,2,3-triazoles.[7] This makes the syntheses of bis-1,2,3-
triazoles more and more interesting.[8]
At the same time, many molecules possessing
2(5H)-furanone moiety, a kind of α,β-unsaturated lac-
tone substructure frequently found in natural products,
have received considerable interests due to the signifi-
cant biological activities, such as antibacterial,[9] anti-
inflammatory,[10] antitumor,[11] anti-parasitic[12] and so
on.[13] In fact, many 2(5H)-furanone compounds with
relatively simple structure are also important organic
intermediates.[14] These made the reports on 2(5H)-
furanone chemistry intensive recently.[11c,15,16]
Futhermore, many bioactive amino acids have been
widely used as building blocks in organic syntheses.[17]
However, the studies on the synthesis of 2(5H)-furanone
derivatives with 1,2,3-triazole and amino acid moieties
have seldom been reported.[16] Herein, on the basis of
our previous research,[16c] a series of new chiral 2(5H)-
furanone derivatives 6 with polyheterocyclic structures
(Scheme 1) were further designed and prepared by the
combination of some bioactive units, such as bis-1,2,3-
triazole, 2(5H)-furanone and especially using dicarboxyl
Experimental
General
All the melting points were determined on an X-5
digital melting points apparatus and were uncorrected.
Infrared spectra were recorded on a Bruker Vector 33
FT-IR instrument by liquid film method in the absorp-
－
tion range of 4000—400 cm . H NMR and 13C NMR
spectra were obtained in CDCl3 on a Varian DRX-400
MHz spectrometer and tetramethylsilane (TMS) was
used as an internal standard. UV absorption peaks were
measured by Shimazu UV-2550 ultraviolet absorption
detector with dichloromethane as a solvent. Optical ro-
tations were determined with an Autopol IV polarimeter
in C2H5OH in a 10 cm cell. Elemental analysis was
performed on a Thermo Flashea TM 112 elemental ana-
lyzer. The mass spectra (MS) were recorded on Thermo
LCQ DECA XP MAX mass spectrometer.
1
1
All reagents and solvents were commercially avail-
able and used as received. Using furfural, natural men-
thol, borneol and bromohydrocarbons as starting mate-
rials, the intermediates (5S)-5-alkoxy-3,4-dihalo-2(5H)-
furanone 1 and azidoalkanes 5 were prepared according
to the literatures [11c, 15f, 16c, 18].
General procedure for the synthesis of compounds 5
A flame-dried 25-mL two-neck flask was charged
*
E-mail: wangzy@scnu.edu.cn or wangwangzhaoyang@tom.com
Received June 28, 2012; accepted September 9, 2012.
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/cjoc.201200638 or from the author.
Chin. J. Chem. 2012, 30, 2411—2422 © 2012 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
2411

Huo et al.
FULL PAPER
with 1.2 mmol amino acid 2 and 3.5 mmol potassium
hydroxide in C2H5OH (10 mL). The resulting suspen-
sion was stirred at 45 ℃ until dissolution. Then, 1.0
mmol intermediates (5S)-5-alkoxy-3,4-dihalo-2(5H)-
furanones 1 in CH2Cl2 (10 mL) was dropped, and the
reaction was stirred at room temperature for 48 h. After
the reaction was finished, the pH value of the reaction
mixture was adjusted to 3—4 with dilute hydrochloric
acid, and then extracted with CH2Cl2 (10 mL×2). The
combined organic layers were dried with anhydrous
magnesium sulfate, and concentrated under vacuum to
give a crude product, which was purified by column
chromatography on silica gel with gradient eluent of
mixtures of petroleum ether and ethyl acetate to afford
the sample 3a—3f for analysis.
doalkanes 5, 0.1 mmol copper sulfate pentahydrate and
0.2 mmol copper powder in CH3CN (5 mL). The mix-
ture was stirred at room temperature, and the reaction
was monitored by TLC. After the completion of the re-
action (about 48 h), the reaction mixture was quenched
with a saturated aqueous solution of NH4Cl (20 mL×3)
and extracted with ethyl acetate (10 mL×3). Then, the
organic layer was dried with anhydrous magnesium
sulfate, and concentrated under vacuum to give a crude
product, which was purified by column chromatography
on silica gel with gradient eluent of mixtures of petro-
leum ether and ethyl acetate to afford the desired com-
pounds 6aa—6bf for analysis.
Spectral data
(S)-2-((S)-4-Chloro-2-((1R,2S,5R)-2-isopropyl-5-
methylcyclohexyloxy)-5-oxo-2,5-dihydrofuran-3-yl-
amino)pentanedioic acid (3a) Yellowish oil, yield
22%; [α]D20 ＋49 (c 0.227, C2H5OH); UV-vis (CH2Cl2)
General procedure for the synthesis of compounds 4
A flame-dried 25-mL round-bottomed flask was
charged with 1.0 mmol N-[5-alkoxy-3-halo-2(5H)-
furanonyl] amino acid 3 and 4.0 mmol anhydrous potas-
sium carbonate in DMSO (5 mL). The resulting suspen-
sion was stirred for 2 h under an atmosphere of nitrogen.
Then, 2.5 mmol propargyl bromides were added and the
reaction was stirred for 12 h at 40 ℃. The resulting
mixture was quenched with a saturated aqueous solution
of NH4Cl (20 mL×3) and extracted with ethyl acetate
(10 mL×3). The combined organic layers were dried
with anhydrous magnesium sulfate, and concentrated
under vacuum to give a crude product, which was puri-
fied by column chromatography on silica gel with gra-
dient eluent of mixtures of petroleum ether and ethyl
acetate to afford the sample 4a—4f for analysis.
λ
max: 263 nm; 1H NMR (400 MHz, CDCl3-TMS) δ: 0.76
(d, J＝6.8 Hz, 3H, CH3), 0.83—0.97 (m, 7H, CH,
2CH3), 1.00—1.21 (m, 2H, CH2), 1.35—1.51 (m, 2H,
CH), 1.62—1.73 (m, 2H, CH2), 1.83—2.05 (m, 2H,
CH2), 2.07—2.31 (m, 2H, CH2), 2.32—2.68 (m, 2H,
CH2), 3.67—3.76 (m, 1H, CH), 4.71—4.87 (m, 1H, CH),
5.75 (b, 1H, NH), 6.32 (s, 1H, CH); 13C NMR (100
MHz, CDCl3-TMS) δ: 14.06, 21.70, 21.95, 23.09, 25.14,
26.06, 31.33, 34.00, 40.67, 42.11, 46.63, 60.82, 74.97,
97.25, 100.80, 164.36, 168.26, 169.11, 172.23; IR
(CH2Cl2) ν: 3363, 2951, 2863, 1780, 1750, 1649, 1348,
－
1
1251, 1199, 955, 748 cm ; MS (ESI) m/z (%): 416
([M－H]－, 100). Anal. calcd for C19H28ClNO7: C 54.56,
H 6.70, N 3.35; found C 54.47, H 6.76, N 3.40.
General procedure for the synthesis of target com-
pounds 6
(S)-2-((S)-4-Bromo-2-((1R,2S,5R)-2-isopropyl-5-
methylcyclohexyloxy)-5-oxo-2,5-dihydrofuran-3-yl-
amino)pentanedioic acid (3b) Yellow oil, yield 39%;
A flame-dried 25-mL round-bottomed flask was
charged with 1.0 mmol N-[5-alkoxy-3-halo-2(5H)-fur-
anonyl] amino acid propargyl esters 4, 2.0 mmol azi-
[α]D20 ＋47 (c 0.164, C2H5OH); UV-vis (CH2Cl2) λmax
:
Scheme 1 The synthetic route of target compounds
X
X
H
COOH
H
HOOC
COOH
O
O
HOOC
O
n
H2N
1a - 1b
(1a: X = Cl; 1b: X = Br)
HN
H
H
X
2a - 2b (2a: n=2; 2b: n=1)
Br
Br
H
KOH, EtOH, r.t.
O
O
R*=
R*O
(M*),
(B*)
R
3a - 3f
O
O
O
1c
N
N
N
N
N
N
R
OOC
OOC
COO
COO
X
n
n
Br
CuSO4 5H2O, Cu
HN
H
HN
X
H
O
K2CO3, DMSO
CH3CN, r.t.
H
H
40 oC
RN3
5a - 5b
O
O
O
R*O
R*O
6aa - 6bf
4a - 4f
N3
N3
5b:
2412
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© 2012 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2012, 30, 2411—2422

Synthesis of 2(5H)-Furanone Derivatives with Bis-1,2,3-triazole Structure
1
267 nm; H NMR (400 MHz, CDCl3-TMS) δ: 0.78 (d,
2.80—3.35 (m, 2H, CH2), 3.42—3.58 (m, 1H, CH),
4.53—4.81 (m, 1H, CH), 5.20 (s, 1H, NH), 5.70 (s, 1H,
CH), 8.45 (b, 2H, 2COOH); 13C NMR (100 MHz,
CDCl3-TMS) δ: 15.85, 21.06, 22.14, 22.94, 25.61, 31.59,
34.03, 40.56, 44.27, 49.58, 60.65, 72.18, 83.70, 99.79,
164.10, 171.78, 173.58, 174.48; IR (CH2Cl2) ν: 3366,
2956, 2873, 1736, 1652, 1376, 1279, 1121, 957, 695
cm ; MS (ESI) m/z (%): 446 ([M－H] , 85). Anal.
calcd for C18H26BrNO5: C 48.18, H 5.80, N 3.12; found
C 48.23, H 5.87, N 3.19.
J＝6.8 Hz, 3H, CH3), 0.83—0.96 (m, 7H, CH, 2CH3),
0.99—1.22 (m, 2H, CH2), 1.32—1.47 (m, 2H, 2CH),
1.63—1.74 (m, 2H, CH2), 1.81—2.07 (m, 2H, CH2),
2.11—2.31 (m, 2H, CH2), 2.37—2.63 (m, 2H, CH2),
3.49—3.70 (m, 1H, CH), 4.69—4.90 (m, 1H, CH), 5.56
(s, 1H, NH), 5.78 (s, 1H, CH), 9.35 (s, 2H, 2COOH);
13C NMR (100 MHz, CDCl3-TMS) δ: 15.68, 20.93,
22.09, 22.78, 25.85, 28.29, 31.59, 34.02, 39.68, 42.19,
47.93, 60.68, 77.46, 82.92, 96.99, 163.44, 167.18,
175.17, 178.16; IR (CH2Cl2) ν: 3330, 2955, 2869, 1742,
－
－
1
(S)-2-((S)-4-Bromo-5-oxo-2-((1S,2R,4S)-1,7,7-
tri-methylbicyclo[2.2.1]heptan-2-yloxy)-2,5-dihydro-
furan-3-ylamino)succinic acid (3f) Yellow oil, yield
43%; [α]D20 ＋21 (c 0.408, C2H5OH); UV-vis (CH2Cl2)
－
1
1647, 1373, 1195, 959, 678 cm ; MS (ESI) m/z (%):
460 ([M－H]－, 30). Anal. calcd for C19H28BrNO7: C
49.32, H 6.06, N 3.03; found C 49.36, H 6.11, N 3.01.
(S)-2-((S)-4-Bromo-5-oxo-2-((1S,2R,4S)-1,7,7-
trimethylbicyclo[2.2.1]heptan-2-yloxy)-2,5-dihydro-
furan-3-ylamino)pentanedioic acid (3c) Brown oil,
yield 32%; [α]2D0 ＋24 (c 0.209, C2H5OH); UV-vis
1
λmax: 267 nm; H NMR (400 MHz, CDCl3-TMS) δ:
0.78—0.88 (m, 6H, 2CH3), 0.91 (s, 3H, CH3),
1.19—1.49 (m, 4H, 2CH2), 1.63—1.74 (m, 2H, CH2),
2.12—2.38 (m, 1H, CH), 2.86—3.37 (m, 2H, CH2),
3.80—3.90 (m, 1H, CH), 4.59—5.03 (m, 1H, CH), 5.89
(s, 1H), 6.02 (s, 1H, NH), 8.50 (b, 2H, 2COOH); 13C
NMR (100 MHz, CDCl3-TMS) δ: 13.77, 18.79, 19.59,
26.43, 27.91, 34.31, 36.63, 37.00, 44.32, 47.57, 49.40,
60.72, 81.38, 88.4, 97.7, 159.5, 162.4, 172.2, 173.62; IR
(CH2Cl2) ν: 3294, 2954, 2882, 1743, 1644, 1324, 1226,
1
(CH2Cl2) λmax: 270 nm; H NMR (400 MHz, CDCl3-
TMS) δ: 0.79—0.88 (m, 6H, 2CH3), 0.906 (s, 3H, CH3),
1.25—1.39 (m, 4H, 2CH2), 1.66—1.80 (m, 2H, CH2),
2.06—2.34 (m, 3H, CH, CH2), 2.44—2.67 (m, 2H, CH2),
4.00 (d, J＝7.6 Hz, 1H, CH), 4.09—4.47 (m, 1H, CH),
5.73 (s, 1H, NH), 5.81 (s, 1H, CH), 7.74 (s, 2H,
2COOH); 13C NMR (100 MHz, CDCl3-TMS) δ: 14.97,
18.74, 19.55, 26.94, 27.89, 28.07, 38.09, 40.56, 44.84,
47.52, 49.37, 58.12, 77.87, 88.12, 99.00, 163.06, 168.44,
174.23, 177.68; IR (CH2Cl2) ν: 3457, 2982, 2953, 2880,
1801, 1744, 1720, 1649, 1306, 1185, 952, 599 cm ;
MS (ESI) m/z (%): 458 ([M－H]－, 80). Anal. calcd for
C19H26BrNO7: C 49.53, H 5.65, N 3.04; found C 49.46,
H 5.70, N 3.08.
－
－
1
1134, 957, 617 cm ; MS (ESI) m/z (%): 444 ([M－H] ,
83). Anal. calcd for C18H24BrNO5: C 48.40, H 5.38, N
3.14; found C 48.34, H 5.23, N 3.17.
(S)-Diprop-2-ynyl-2-((S)-4-chloro-2-((1R,2S,5R)-
2-isopropyl-5-methylcyclohexyloxy)-5-oxo-2,5-dihy-
dro-furan-3-ylamino)pentanedioate (4a) Brown oil,
yield 28%, [α]2D0 ＋59 (c 0.233, C2H5OH); UV-vis
－
1
1
(CH2Cl2) λmax: 267 nm; H NMR (400 MHz, CDCl3-
(S)-2-((S)-4-Chloro-2-((1R,2S,5R)-2-isopropyl-5-
methylcyclohexyloxy)-5-oxo-2,5-dihydrofuran-3-yl-
amino)succinic acid (3d) Brown oil, yield 40%;
TMS) δ: 0.75—0.93 (m, 10H, CH, 3CH3), 0.99—1.11
(m, 2H, CH2), 1.33—1.43 (m, 2H, 2CH), 1.66—1.71 (m,
2H, CH2), 1.85—2.02 (m, 2H, CH2), 2.22—2.31 (m, 2H,
CH2), 2.50—2.55 (m, 4H, CH2, 2CH), 3.66—3.74 (m,
1H, CH), 4.70—4.80 (m, 5H, CH, 2CH2), 5.76 (s, 1H,
NH), 5.95 (s, 1H, CH); 13C NMR (100 MHz,
CDCl3-TMS) δ: 15.26, 21.00, 22.09, 23.03, 25.04, 25.83,
29.68, 31.39, 34.17, 42.26, 47.71, 52.49, 53.56, 59.51,
75.38, 76.05, 76.22, 77.12, 79.09, 93.14, 96.17, 162.99,
167.2, 170.3, 173.7; IR (CH2Cl2) ν: 3379, 3288, 2954,
2929, 2864, 2133, 1748, 1658, 1376, 1175, 1122, 966,
757, 645 cm－1; MS (ESI) m/z (%): 492 ([M－
H]－, 100). Anal. calcd for C25H32ClNO7: C 60.73, H
6.48, N 2.83; found 60.75, H 6.42, N 2.89.
[α]D20 －33 (c 0.361, C2H5OH); UV-vis (CH2Cl2) λmax
:
1
264 nm; H NMR (400 MHz, CDCl3-TMS) δ: 0.78 (d,
J＝5.2 Hz, 3H, CH3), 0.79—0.96 (m, 7H, CH, 2CH3),
0.98—1.14 (m, 2H, CH2), 1.26—1.47 (m, 2H, 2CH),
1.61—1.74 (m, 2H, CH2), 1.98—2.26 (m, 2H, CH2),
2.87—3.35 (m, 2H, CH2), 3.50—3.67 (m, 1H, CH),
4.58—4.87 (m, 1H, CH), 5.83 (s, 1H, NH), 5.86 (s, 1H,
CH), 8.11 (b, 2H, 2COOH); 13C NMR (100 MHz,
CDCl3-TMS) δ: 15.62, 20.83, 22.10, 22.81, 25.63, 31.33,
33.90, 37.33, 42.22, 47.89, 60.62, 77.25, 83.03, 98.69,
167.84, 168.16, 173.30, 174.41; IR (CH2Cl2) ν: 3412,
2979, 2954, 2873, 1775, 1644, 1363, 1253, 1148, 960,
(S)-Diprop-2-ynyl-2-((S)-4-bromo-2-((1R,2S,5R)-
2-isopropyl-5-methylcyclohexyloxy)-5-oxo-2,5-dihy-
drofuran-3-ylamino)pentanedioate (4b) Yellowish
oil, yield 70%, [α]2D0 ＋29 (c 0.355, C2H5OH); UV-vis
－
－
1
746 cm ; MS (ESI) m/z (%): 402 ([M－H] , 100).
Anal. calcd for C18H26ClNO5: C 53.49, H 6.44, N 3.47;
found C 53.51, H 6.50, N 3.39.
1
(S)-2-((S)-4-Bromo-2-((1R,2S,5R)-2-isopropyl-5-
methylcyclohexyloxy)-5-oxo-2,5-dihydrofuran-3-yl-
amino)succinic acid (3e) Brown oil, yield 33%;
(CH2Cl2) λmax: 271 nm; H NMR (400 MHz, CDCl3-
TMS) δ: 0.75 (d, J＝6.8 Hz, 3H, CH3), 0.84—0.96 (m,
7H, CH, 2CH3), 0.99—1.14 (m, 2H, CH2), 1.27—1.40
(m, 2H, 2CH), 1.65—1.70 (m, 2H, CH2), 1.88—2.01 (m,
2H, CH2), 2.22—2.32 (m, 2H, CH2), 2.48—2.57 (m, 4H,
CH2, 2CH), 3.57—3.71 (m, 1H, CH), 4.69—4.80 (m,
[α]D20 ＋88 (c 0.117, C2H5OH); UV-vis (CH2Cl2) λmax
:
1
264 nm; H NMR (400 MHz, CDCl3-TMS) δ: 0.79 (d,
J＝6.8 Hz, 3H, CH3), 0.84—0.98 (m, 7H, CH, 2CH3),
0.99—1.16 (m, 2H, CH2), 1.32—1.49 (m, 2H, 2CH),
1.61—1.76 (m, 2H, CH2), 1.97—2.22 (m, 2H, CH2),
5H, CH, 2CH2), 5.45 (s, 1H, NH), 5.77 (s, 1H, CH); 13
C
NMR (100 MHz, CDCl3-TMS) δ: 15.78, 21.01, 22.09,
Chin. J. Chem. 2012, 30, 2411—2422
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Huo et al.
FULL PAPER
22.81, 25.83, 26.89, 29.82, 31.62, 33.90, 42.28, 47.98,
52.48, 53.55, 60.68, 75.38, 76.22, 76.37, 77.13, 79.09,
82.59, 97.27, 162.46, 164.44, 170.18, 171.57; IR
(CH2Cl2) ν: 3393, 3281, 2962, 2915, 2870, 2130, 1755,
1644, 1382, 1187, 1116, 960, 633, 522 cm ; MS (ESI)
m/z (%): 538 ([M ＋ H] ＋ , 88). Anal. calcd for
C25H32BrNO7: C 55.72, H 5.94, N 2.60; found C 55.76,
H 5.91, N 2.73.
CDCl3-TMS) δ: 15.95, 21.02, 22.09, 22.91, 25.83, 31.60,
33.93, 40.23, 42.40, 48.01, 50.18, 52.87, 53.39, 77.28,
77.55, 77.97, 78.97, 79.24, 82.98, 99.45, 160.12, 167.44,
171.83, 172.01; IR (CH2Cl2) ν: 3464, 3300, 2950, 2925,
2870, 2139, 1742, 1650, 1316, 1182, 1125, 937, 632,
528 cm ; MS (ESI) m/z (%): 524 ([M＋H] , 46.0).
Anal. calcd for C24H30BrNO7: C 54.92, H 5.72, N 2.67;
found C 54.88, H 5.69, N 2.78.
－
1
－
＋
1
(S)-Diprop-2-ynyl-2-((S)-4-bromo-5-oxo-2-((1S,
2R,4S)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-yloxy)-
(S)-Diprop-2-ynyl-2-((S)-4-bromo-5-oxo-2-((1S,
2R,4S)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-yloxy)-
2,5-dihydrofuran-3-ylamino)succinate (4f) Brown
oil, yield 55%, [α]2D0 ＋65 (c 0.109, C2H5OH); UV-vis
2,5-dihydrofuran-3-ylamino)pentanedioate
(4c)
Yellow oil, yield 62%, [α]D20 ＋72 (c 0.085, C2H5OH);
1
1
UV-vis (CH2Cl2) λmax: 267 nm; H NMR (400 MHz,
(CH2Cl2) λmax: 264 nm; H NMR (400 MHz, CDCl3-
CDCl3-TMS) δ: 0.86 (s, 3H, CH3), 0.87 (s, 3H, CH3),
0.93 (s, 3H, CH3), 1.25—1.30 (m, 4H, 2CH2),
1.66—1.80 (m, 2H, CH2), 2.14—2.33 (m, 3H, CH, CH2),
2.51—2.55 (m, 4H, CH2, 2CH), 4.01 (d, J＝8.8 Hz, 1H,
CH), 4.62—4.85 (m, 5H, CH, 2CH2), 5.49 (s, 1H, NH),
5.77 (s, 1H, CH); 13C NMR (100 MHz, CDCl3-TMS) δ:
13.87, 18.78, 19.59, 26.54, 27.93, 28.18, 29.14, 37.13,
44.82, 47.61, 49.46, 52.50, 53.49, 54.58, 75.40, 76.11,
76.37, 77.09, 77.65, 88.28, 99.42, 157.84, 167.04,
170.20, 171.67; IR (CH2Cl2) ν: 3386, 3294, 2981, 2955,
2884, 2114, 1762, 1638, 1396, 1194, 1142, 967, 626,
TMS) δ: 0.87 (s, 6H, 2CH3), 0.90 (s, 3H, CH3), 1.22—
1.29 (m, 4H, 2CH2), 1.65—1.77 (m, 2H, CH2),
2.05—2.18 (m, 1H, CH), 2.24—2.56 (m, 2H, 2CH2),
3.00—3.03 (m, 2H, CH2), 4.00 (d, J＝7.2 Hz, 1H, CH),
4.68—4.87 (m, 5H, CH, 2CH2), 5.82 (s, 1H, NH), 6.12
(s, 1H, CH); 13C NMR (100 MHz, CDCl3-TMS) δ:
13.91, 18.77, 19.59, 26.47, 27.91, 37.19, 39.56, 44.79,
47.57, 50.08, 52.08, 52.83, 53.48, 75.78, 76.01, 76.47,
76.74, 79.29, 87.71, 98.58, 158.68, 168.51, 169.50,
171.46; IR (CH2Cl2) ν: 3471, 3290, 2981, 2953, 2880,
2130, 1742, 1658, 1337, 1176, 1129, 972, 644, 588
－
＋
－
＋
1
1
547 cm ; MS (ESI) m/z (%): 536 ([M＋H] , 85), 558
([M＋Na]＋, 81). Anal. calcd for C25H32BrNO7: C 55.93,
H 5.59, N 2.61; found C 55.98, H 5.63, N 2.57.
cm ; MS (ESI) m/z (%): 522 ([M＋H] , 100). Anal.
calcd for C24H28BrNO7: C 55.13, H 5.36, N 2.68; found
C 55.11, H 5.41, N 2.63.
(S)-Diprop-2-ynyl-2-((S)-4-chloro-2-((1R,2S,5R)-
2-isopropyl-5-methylcyclohexyloxy)-5-oxo-2,5-dihy-
dro-furan-3-ylamino)succinate (4d) Brown oil, yield
43%, [α]D20 ＋60 (c 0.136, C2H5OH); UV-vis (CH2Cl2)
(S)-Bis((1-benzyl-1H-1,2,3-triazol-4-yl)methyl)-2-
((S)-4-chloro-2-((1R,2S,5R)-2-isopropyl-5-methyl-
cyclohexyloxy)-5-oxo-2,5-dihydrofuran-3-ylamino)-
pentanedioate (6aa) Yellow oil, yield 66%; [α]2D0
＋76 (c 0.082, C2H5OH); UV-vis (CH2Cl2) λmax: 270 nm;
1H NMR (400 MHz, CDCl3-TMS) δ: 0.73—0.91 (m,
10H, CH, 3CH3), 0.98—1.09 (m, 2H, CH2), 1.33—1.42
(m, 2H, 2CH), 1.61—1.68 (m, 2H, CH2), 1.96—2.11 (m,
2H, CH2), 2.18—2.30 (m, 2H, CH2), 2.31—2.48 (m, 2H,
CH2), 3.54—3.65 (m, 1H, CH), 4.70—4.86 (m, 1H,
NH), 5.20—5.37 (m, 5H, CH, 2CH2), 5.52 (s, 4H,
2CH2), 5.66 (s, 1H, CH), 7.25—7.41 (m, 10H, 2PhH),
7.53 (s, 2H); 13C NMR (100 MHz, CDCl3-TMS) δ:
14.16, 20.96, 22.08, 22.71, 25.81, 28.16, 29.72, 31.42,
33.60, 42.29, 47.95, 54.23, 54.25, 58.30, 58.60, 61.09,
77.24, 84.61, 98.66, 123.61, 123.70, 128.18, 128.22,
128.81, 128.89, 129.14, 129.17, 134.37, 134.92, 142.26,
142.99, 165.60, 166.44, 171.65, 172.21; IR (CH2Cl2) ν:
3359, 3144, 3078, 3037, 2961, 2915, 2857, 1748, 1664,
1555, 1497, 1459, 1370, 1181, 1116, 966, 796, 723, 698
1
λmax: 265 nm; H NMR (400 MHz, CDCl3-TMS) δ:
0.82—0.84 (m, 3H, CH3), 0.88—0.95 (m, 7H, CH,
2CH3), 0.97—1.10 (m, 2H), 1.25—1.37 (m, 2H, 2CH),
1.63—1.70 (m, 2H, CH2), 1.96—2.13 (m, 2H, CH2),
2.24—2.54 (m, 2H, 2CH), 2.98—3.19 (m, 2H, CH2),
3.53—3.58 (m, 1H, CH), 4.70—4.80 (m, 5H, CH,
2CH2), 5.57 (s, 1H, NH), 5.72 (s, 1H, CH); 13C NMR
(100 MHz, CDCl3-TMS) δ: 15.97, 20.99, 22.07, 22.94,
25.94, 31.62, 33.93, 38.80, 42.44, 48.01, 51.59, 52.81,
53.82, 75.78, 76.14, 76.29, 76.60, 83.14, 91.36, 98.61,
156.71, 166.88, 168.98, 170.78; IR (CH2Cl2) ν: 3476,
3307, 2954, 2909, 2864, 2127, 1761, 1664, 1331, 1187,
－
1
1136, 946, 737, 626 cm ; MS (ESI) m/z (%): 478 ([M
－H]－, 46). Anal. calcd for C24H30ClNO7: C 60.00, H
6.25, N 2.92; found C 60.13, H 6.21, N 2.94.
(S)-Diprop-2-ynyl-2-((S)-4-bromo-2-((1R,2S,5R)-
2-isopropyl-5-methylcyclohexyloxy)-5-oxo-2,5-dihy-
drofuran-3-ylamino)succinate (4e) Yellow oil, yield
69%, [α]D20 ＋ 107 (c 0.177, C2H5OH); UV-vis
－
－
1
cm ; MS (ESI) m/z (%): 759 ([M－H] , 100). Anal.
calcd for C39H46ClN7O7: C 61.66, H 6.06, N 12.91;
found C 61.72, H 6.11, N 12.87.
(CH2Cl2) λmax
:
261 nm; 1H NMR (400 MHz,
(S)-Bis((1-benzyl-1H-1,2,3-triazol-4-yl)methyl)-2-
((S)-4-bromo-2-((1R,2S,5R)-2-isopropyl-5-methyl-
cyclohexyloxy)-5-oxo-2,5-dihydrofuran-3-ylamino)-
pentanedioate (6ab) Yellow oil, yield 63%; [α]2D0
＋121 (c 0.053, C2H5OH); UV-vis (CH2Cl2) λmax: 270
CDCl3-TMS) δ: 0.83 (d, J ＝ 7.2 Hz, 3H, CH3),
0.86—0.95 (m, 7H, CH, 2CH3), 0.98—1.11 (m, 2H,
CH2), 1.28—1.40 (m, 2H, 2CH), 1.66—1.69 (m, 2H,
CH2), 2.05—2.15 (m, 2H, CH2), 2.24—2.52 (m, 2H,
2CH), 2.96—3.18 (m, 2H, CH2), 3.53—3.60 (m, 1H,
CH), 4.58—4.84 (m, 4H, 2CH2), 5.06—5.13 (m, 2H,
NH, CH), 5.74 (s, 1H, CH); 13C NMR (100 MHz,
1
nm; H NMR (400 MHz, CDCl3-TMS) δ: 0.69 (d, J＝
6.4 Hz, 3H, CH3), 0.76—0.85 (m, 7H, CH, 2CH3), 0.88
—1.03 (m, 2H, CH2), 1.24—1.43 (m, 2H, 2CH), 1.53—
2414
www.cjc.wiley-vch.de
© 2012 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2012, 30, 2411—2422

Synthesis of 2(5H)-Furanone Derivatives with Bis-1,2,3-triazole Structure
1.64 (m, 2H, CH2), 1.95—2.07 (m, 2H, CH2), 2.09—
2.22 (m, 2H, CH2), 2.26—2.42 (m, 2H, CH2), 3.43—
3.62 (m, 1H, CH), 4.75 (b, 1H, NH), 4.98—5.29 (m, 5H,
CH, 2CH2), 5.44 (s, 4H, 2CH2), 5.46 (s, 1H, CH), 7.18
—7.32 (m, 10H, 2PhH), 7.50 (s, 2H, 2CH); 13C NMR
(100 MHz, CDCl3-TMS) δ: 15.74, 20.96, 22.11, 22.79,
25.74, 28.16, 29.10, 31.58, 33.87, 42.25, 47.93, 54.23,
54.25, 58.05, 58.98, 61.06, 77.33, 82.59, 99.19, 123.70,
124.03, 128.15, 128.19, 128.85, 128.91, 129.14, 129.18,
134.22, 134.34, 142.58, 142.58, 161.83, 167.53, 170.63,
172.24; IR (CH2Cl2) ν: 3320, 3144, 3066, 3027, 2954,
2923, 2857, 1755, 1650, 1533, 1500, 1455, 1324, 1181,
m/z (%): 744 ([M － H] － , 100). Anal. calcd for
C38H44ClN7O7: C 61.11, H 5.76, N 13.13; found C
61.29, H 5.68, N 13.18.
(S)-Bis((1-benzyl-1H-1,2,3-triazol-4-yl)methyl)-2-
((S)-4-bromo-2-((1R,2S,5R)-2-isopropyl-5-methyl-
cyclohexyloxy)-5-oxo-2,5-dihydrofuran-3-ylamino)-
succinate (6ae) Yellowish oil, yield 69%; [α]2D0
－52 (c 0.038, C2H5OH); UV-vis (CH2Cl2) λmax: 266 nm;
1H NMR (400 MHz, CDCl3-TMS) δ: 0.76 (d, J＝6.8 Hz,
3H, CH3), 0.82—0.94 (m, 7H, CH, 2CH3), 0.96—1.10
(m, 2H, CH2), 1.27—1.39 (m, 2H, 2CH), 1.61—1.70 (m,
2H, CH2), 1.99—2.14 (m, 2H, CH2), 2.85—3.10 (m, 2H,
CH2), 3.50—3.61 (m, 1H, CH), 4.94—5.31 (m, 5H, CH,
2CH2), 5.52 (s, 2H, CH2), 5.54 (s, 2H, CH2), 5.70—5.78
(m, 1H, NH), 5.84 (s, 1H, CH), 7.10—7.42 (m, 10H,
2PhH), 7.49 (s, 1H, CH), 7.57 (s, 1H, CH); 13C NMR
(100 MHz, CDCl3-TMS) δ: 15.56, 20.96, 22.12, 22.73,
25.56, 31.57, 33.90, 37.53, 42.24, 47.87, 51.54, 54.08,
54.24, 58.31, 59.21, 82.97, 94.50, 99.43, 123.55, 124.07,
128.16, 128.18, 128.88, 128.91, 129.13, 129.16, 134.24,
134.32, 141.91, 142.22, 159.99, 167.25, 169.52, 169.81;
IR (CH2Cl2) ν: 3359, 3152, 3072, 3033, 2954, 2926,
2870, 1761, 1664, 1527, 1494, 1455, 1331, 1187, 1128,
－
1
1122, 946, 737, 698, 587 cm ; MS (ESI) m/z (%): 803
([M－H]－, 35). Anal. calcd for C39H46BrN7O7: C 58.28,
H 5.73, N 12.20; found C 58.46, H 5.77, N 12.25.
(S)-Bis((1-benzyl-1H-1,2,3-triazol-4-yl)methyl)-2-
((S)-4-bromo-5-oxo-2-((1S,2R,4S)-1,7,7-trimethyl-
bicyclo[2.2.1]heptan-2-yloxy)-2,5-dihydrofuran-3-
ylamino)pentanedioate (6ac) Yellowish oil, yield
54%; [α]D20 ＋66 (c 0.044, C2H5OH); UV-vis (CH2Cl2)
λmax: 269 nm; 1H NMR (400 MHz, CDCl3-TMS) δ: 0.76
—0.91 (m, 9H, 3CH3), 1.20—1.34 (m, 4H, 2CH2), 1.61
—1.70 (m, 2H, CH2), 2.04—2.09 (m, 1H, CH), 2.15—
2.24 (m, 2H, CH2), 2.34—2.43 (m, 2H, CH2), 3.96 (d,
J＝8.4 Hz, 1H, CH), 4.77 (b, 1H, NH), 5.09—5.35 (m,
5H, CH, 2CH2), 5.52 (s, 4H, 2CH2), 5.71 (s, 1H, CH),
7.23—7.42 (m, 10H, 2PhH), 7.57 (s, 2H, 2CH); 13C
NMR (100 MHz, CDCl3-TMS) δ: 13.77, 18.79, 19.61,
26.43, 27.90, 29.39, 31.58, 37.91, 44.75, 47.57, 49.40,
54.23, 54.83, 58.04, 58.93, 60.41, 77.33, 80.12, 99.41,
123.67, 123.97, 128.14, 128.19, 128.84, 128.91, 129.14,
129.18, 134.23, 134.34, 141.96, 142.56, 158.49, 167.36,
170.64, 172.15; IR (CH2Cl2) ν: 3314, 3151, 3060, 3033,
2962, 2935, 2864, 1736, 1644, 1566, 1494, 1462, 1318,
－
1
940, 723, 692, 575 cm ; MS (ESI) m/z (%): 812 ([M＋
Na]＋, 85). Anal. calcd for C38H44BrN7O7: C 57.67, H
5.56, N 12.39; found C 56.85, H 5.61, N 12.44.
(S)-Bis((1-benzyl-1H-1,2,3-triazol-4-yl)methyl)-2-
((S)-4-bromo-5-oxo-2-((1S,2R,4S)-1,7,7-trime-
thylbicyclo[2.2.1]heptan-2-yloxy)-2,5-dihydrofuran-
3-ylamino)succinate (6af) White powder, yield 59%,
m.p. 103.7 — 105.2 ℃ ; [α]D20 ＋ 118 (c 0.063,
1
C2H5OH); UV-vis (CH2Cl2) λmax: 263 nm; H NMR
(400 MHz, CDCl3-TMS) δ: 0.80 (s, 3H, CH3), 0.82 (s,
3H, CH3), 0.84 (s, 3H, CH3), 1.19—1.34 (m, 4H, 2CH2),
1.62—1.71 (m, 2H, CH2), 2.05—2.22 (m, 1H, CH),
2.96—3.11 (m, 2H, CH2), 3.96 (d, J＝6.8 Hz, 1H, CH),
5.03—5.34 (m, 5H, CH, 2CH2), 5.53 (s, 4H, 2CH2),
5.69 (s, 1H, NH), 5.71 (s, 1H, CH), 7.25—7.41 (m, 10H,
2PhH), 7.52 (s, 1H, CH), 7.58 (s, 1H, CH); 13C NMR
(100 MHz, CDCl3-TMS) δ: 13.74, 18.77, 19.58, 26.35,
27.87, 37.02, 37.44, 44.78, 47.54, 49.37, 54.24, 58.28,
59.14, 60.45, 77.31, 84.59, 99.48, 123.75, 124.08,
127.61, 128.15, 128.18, 128.88, 129.16, 130.25, 134.20,
134.27, 141.92, 142.17, 163.58, 167.90, 169.70, 169.80;
IR (CH2Cl2) ν: 3353, 3191, 3053, 3033, 2948, 2876,
1748, 1638, 1507, 1462, 1331, 1181, 1128, 960, 717,
－
1
1187, 1116, 952, 731, 692, 581 cm ; MS (ESI) m/z (%):
802 ([M＋H]＋, 25), 824 ([M＋Na]＋, 100). Anal. calcd
for C39H44BrN7O7: C 58.30, H 5.48, N 12.21; found C
58.51, H 5.53, N 12.18.
(S)-Bis((1-benzyl-1H-1,2,3-triazol-4-yl)methyl)-2-
((S)-4-chloro-2-((1R,2S,5R)-2-isopropyl-5-methyl-
cyclohexyloxy)-5-oxo-2,5-dihydrofuran-3-ylamino)-
succinate (6ad) Brown oil, yield 52%; [α]D20 ＋70 (c
1
0.055, C2H5OH); UV-vis (CH2Cl2) λmax: 260 nm; H
NMR (400 MHz, CDCl3-TMS) δ: 0.81 (d, J＝6.8 Hz,
3H, CH3), 0.85—0.93 (m, 7H, CH, 2CH3), 0.96—1.09
(m, 2H, CH2), 1.31—1.38 (m, 2H, 2CH), 1.64—1.70 (m,
2H, CH2), 1.94—2.11 (m, 2H, CH2), 2.91—3.02 (m, 2H,
CH2), 3.52—3.58 (m, 1H, CH), 4.79—5.18 (m, 5H, CH,
2CH2), 5.22—5.33 (m, 1H, CH), 5.51 (s, 4H, 2CH2),
5.72 (s, 1H, CH), 6.98—7.46 (m, 10H, 2PhH), 7.55 (s,
2H, 2CH); 13C NMR (100 MHz, CDCl3-TMS) δ: 15.95,
21.01, 22.08, 22.93, 25.86, 31.61, 33.93, 40.27, 42.41,
48.02, 50.08, 54.24, 54.32, 62.02, 62.12, 83.02, 90.89,
98.61, 124.40, 125.34, 128.15, 128.18, 128.84, 128.91,
129.10, 129.16, 134.15, 134.39, 142.06, 144.43, 156.97,
167.05, 169.40, 171.75; IR (CH2Cl2) ν: 3347, 3183,
3144, 3072, 2954, 2929, 2870, 1755, 1677, 1507, 1455,
－
＋
1
614, 575 cm ; MS (ESI) m/z (%): 810 ([M＋Na] , 56);
Anal. calcd for C38H42BrN7O7: C 57.82, H 5.33, N
12.43; found C 57.87, H 5.20, N 12.54.
(S)-Bis((1-hexyl-1H-1,2,3-triazol-4-yl)methyl)-2-
((S)-4-chloro-2-((1R,2S,5R)-2-isopropyl-5-methyl-
cyclohexyloxy)-5-oxo-2,5-dihydrofuran-3-ylamino)-
pentanedioate (6ba) Yellow oil, yield 66%; [α]2D0
＋58 (c 0.031, C2H5OH); UV-vis (CH2Cl2) λmax: 268 nm;
1H NMR (400 MHz, CDCl3-TMS) δ: 0.73—0.92 (m,
16H, CH, 5CH3), 0.95—1.03 (m, 2H, CH2), 1.25—1.34
(m, 12H, 6CH2), 1.38—1.47 (m, 2H, 2CH), 1.66—1.71
(m, 2H, CH2), 1.76—2.06 (m, 6H, 3CH2), 2.14—2.27
－
1
1324, 1175, 1136, 946, 790, 743, 704 cm ; MS (ESI)
Chin. J. Chem. 2012, 30, 2411—2422
© 2012 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
www.cjc.wiley-vch.de
2415

Huo et al.
FULL PAPER
(m, 2H, 2CH), 2.46—2.57 (m, 2H, 2CH), 3.63—3.74
(m, 1H, CH), 4.28—4.38 (m, 4H, 2CH2), 5.05—5.44 (m,
5H, CH, 2CH2), 5.54—6.04 (m, 2H, NH, CH), 7.66 (s,
2H, 2CH); 13C NMR (100 MHz, CDCl3-TMS) δ: 13.95,
15.73, 20.91, 22.08, 22.39, 22.82, 25.21, 26.10, 29.68,
30.16, 31.10, 31.40, 31.58, 34.06, 42.27, 47.70, 50.06,
50.58, 58.44, 58.83, 59.42, 79.28, 82.60, 96.27, 122.66,
124.10, 140.83, 141.57, 162.28, 167.05, 169.26, 170.79;
IR (CH2Cl2) ν: 3269, 3152, 2968, 2923, 2857, 1748,
1650, 1455, 1376, 1175, 1136, 960, 751 cm ; MS (ESI)
m/z (%): 770 ([M ＋ Na] ＋ , 100). Anal. calcd for
C37H58ClN7O7: C 64.27, H 7.75, N 13.10; found C
64.39, H 7.70, N 13.26.
((S)-4-chloro-2-((1R,2S,5R)-2-isopropyl-5-methyl-
cyclohexyloxy)-5-oxo-2,5-dihydrofuran-3-ylamino)-
succinate (6bd) Red oil, yield 66%; [α]D20 ＋76 (c
1
0.063, C2H5OH); UV-vis (CH2Cl2) λmax: 271 nm; H
NMR (400 MHz, CDCl3-TMS) δ: 0.80—0.93 (m, 16H,
CH, 5CH3), 0.95—1.03 (m, 2H, CH2), 1.28—1.37 (m,
12H, 6CH2), 1.38—1.46 (m, 2H, 2CH), 1.66—1.71 (m,
2H, CH2), 1.86—1.95 (m, 4H, 2CH2), 1.99—2.13 (m,
2H, CH2), 2.95—3.11 (m, 2H, CH2), 3.54—3.60 (m, 1H,
CH), 4.31—4.40 (m, 4H, 2CH2), 4.96—5.31 (m, 5H,
CH, 2CH2), 5.62—5.71 (m, 1H, NH), 5.74 (s, 1H, CH),
7.59 (s, 1H, CH), 7.65 (s, 1H, CH); 13C NMR (100 MHz,
CDCl3-TMS) δ: 13.96, 15.93, 20.99, 22.06, 22.41, 22.93,
25.89, 26.13, 30.22, 31.11, 31.61, 33.93, 37.49, 42.41,
48.02, 50.53, 51.72, 52.37, 58.44, 59.32, 83.06, 91.10,
98.60, 123.45, 124.01, 141.49, 141.85, 156.83, 166.92,
169.66, 171.45; IR (CH2Cl2) ν: 3328, 3216, 3144, 2962,
2935, 2870, 1755, 1664, 1519, 1460, 1324, 1187, 1128,
－
1
(S)-Bis((1-hexyl-1H-1,2,3-triazol-4-yl)methyl)-2-
((S)-4-bromo-2-((1R,2S,5R)-2-isopropyl-5-methyl-
cyclohexyloxy)-5-oxo-2,5-dihydrofuran-3-ylamino)-
pentanedioate (6bb) Yellow oil, yield 59%; [α]2D0
＋93 (c 0.087, C2H5OH); UV-vis (CH2Cl2) λmax: 270 nm;
1H NMR (400 MHz, CDCl3-TMS) δ: 0.68—0.93 (m,
16H, CH, 5CH3), 0.96—1.12 (m, 2H, CH2), 1.22—1.31
(m, 12H, 6CH2), 1.34—1.47 (m, 2H, 2CH), 1.58—1.69
(m, 2H, CH2), 1.76—2.07 (m, 6H, 3CH2), 2.14—2.27
(m, 2H, CH2), 2.37—2.50 (m, 2H, CH2), 3.54—3.67 (m,
1H, CH), 4.25—4.37 (m, 4H, 2CH2), 5.06—5.39 (m, 5H,
CH, 2CH2), 5.48—5.61 (m, 1H, NH), 5.72 (s, 1H, CH),
7.58 (s, 1H, CH), 7.62 (s, 1H, CH); 13C NMR (100 MHz,
CDCl3-TMS) δ: 13.94, 15.75, 20.97, 22.07, 22.39, 22.78,
25.78, 26.11, 29.16, 30.19, 31.07, 31.09, 31.59, 33.87,
42.28, 47.94, 50.46, 50.50, 58.13, 58.42, 59.09, 79.29,
82.01, 99.21, 123.60, 123.91, 141.41, 142.18, 163.62,
166.32, 170.70, 172.17; IR (CH2Cl2) ν: 3347, 3144,
3099, 2954, 2929, 2864, 1736, 1638, 1519, 1461, 1363,
－
＋
1
952, 743 cm ; MS (ESI) m/z (%): 756 ([M＋Na] ,
100). Anal. calcd for C36H56ClN7O7: C 58.83, H 7.63, N
13.35; found C 58.79, H 7.77, N 13.41.
(S)-Bis((1-hexyl-1H-1,2,3-triazol-4-yl)methyl)-2-
((S)-4-bromo-2-((1R,2S,5R)-2-isopropyl-5-methyl-
cyclohexyloxy)-5-oxo-2,5-dihydrofuran-3-ylamino)-
succinate (6be) Brown oil, yield 48%; [α]D20 ＋72 (c
1
0.016, C2H5OH); UV-vis (CH2Cl2) λmax: 269 nm; H
NMR (400 MHz, CDCl3-TMS) δ: 0.75 (d, J＝6.4 Hz,
3H, CH3), 0.77—0.92 (m, 13H, CH, 4CH3), 0.95—1.07
(m, 2H, CH2), 1.14—1.42 (m, 14H, 2CH, 6CH2),
1.56—1.66 (m, 2H, CH2), 1.74—1.94 (m, 4H, 2CH2),
2.04—2.21 (m, 2H, CH2), 2.69—3.04 (m, 2H, CH2),
3.52—3.63 (m, 1H, CH), 4.17—4.42 (m, 4H, 2CH2),
4.99—5.49 (m, 5H, CH, 2CH2), 5.73 (s, 1H, CH), 5.80
(s, 1H, NH), 7.63 (s, 2H, 2CH); 13C NMR (100 MHz,
CDCl3-TMS) δ: 13.94, 15.90, 21.00, 22.08, 22.38, 22.87,
25.67, 26.09, 30.19, 31.09, 31.56, 33.93, 40.13, 42.40,
48.01, 50.49, 52.08, 52.81, 58.34, 59.26, 78.87, 82.70,
99.40, 123.74, 124.01, 141.38, 141.69, 160.48, 167.60,
168.55, 169.88; IR (CH2Cl2) ν: 3334, 3203, 3138, 2962,
2929, 2864, 1755, 1664, 1461, 1318, 1175, 1128, 940,
－
1
1187, 1116, 952, 626 cm ; MS (ESI) m/z (%): 814 ([M
＋Na]＋, 100). Anal. calcd for C37H58BrN7O7: C 56.00,
H 7.32, N 12.36; found: C 56.14, H 7.29, N 12.40.
(S)-Bis((1-hexyl-1H-1,2,3-triazol-4-yl)methyl)-2-
((S)-4-bromo-5-oxo-2-((1S,2R,4S)-1,7,7-trimethyl-
bicyclo[2.2.1]heptan-2-yloxy)-2,5-dihydrofuran-3-
ylamino)pentanedioate (6bc) Yellow oil, yield 56%;
[α]D20 ＋73 (c 0.064, C2H5OH); UV-vis (CH2Cl2) λmax
:
－
＋
273 nm; 1H NMR (400 MHz, CDCl3-TMS) δ:
0.65—0.95 (m, 15H, 5CH3), 1.03—1.38 (m, 16H,
8CH2), 1.58—1.69 (m, 2H, CH2), 1.76—1.91 (m, 4H,
2CH2), 2.07—2.25 (m, 3H, CH, CH2), 2.36—2.48 (m,
2H, CH2), 3.91 (d, J＝7.2 Hz, 1H, CH), 4.18—4.36 (m,
4H, 2CH2), 4.83—5.29 (m, 5H, CH, 2CH2), 5.46—5.59
(m, 1H, NH), 5.67 (s, 1H, CH), 7.58 (s, 2H, 2CH); 13C
NMR (100 MHz, CDCl3-TMS) δ: 13.80, 13.95, 18.77,
19.58, 22.40, 26.11, 26.44, 27.95, 29.44, 30.21, 31.07,
31.10, 37.11, 44.77, 47.58, 49.42, 50.45, 50.50, 54.88,
58.15, 59.06, 77.29, 88.16, 99.93, 123.65, 123.94,
141.67, 142.01, 163.85, 169.21, 170.71, 172.24; IR
(CH2Cl2) ν: 3308, 3132, 2968, 2923, 2876, 1761, 1650,
606 cm ; MS (ESI) m/z (%): 800 ([M＋Na] , 75).
Anal. calcd for C36H56BrN7O7: C 55.47, H 7.19, N
12.58; found C 55.64, H 7.22, N 12.61.
1
(S)-Bis((1-hexyl-1H-1,2,3-triazol-4-yl)methyl)-2-
((S)-4-bromo-5-oxo-2-((1S,2R,4S)-1,7,7-trimethyl-
bicyclo[2.2.1]heptan-2-yloxy)-2,5-dihydrofuran-3-
ylamino)succinate (6bf)
Yellow oil, yield 67%;
[α]D20 ＋160 (c 0.036, C2H5OH); UV-vis (CH2Cl2) λmax
:
262 nm; 1H NMR (400 MHz, CDCl3-TMS) δ:
0.77—0.86 (m, 15H, 5CH3), 1.10—1.33 (m, 16H,
8CH2), 1.59—1.66 (m, 2H, CH2), 1.80—1.93 (m, 4H,
2CH2), 2.17—2.24 (m, 1H, CH), 2.94—3.11 (m, 2H,
CH2), 3.95 (d, J＝9.2 Hz, 1H, CH), 4.24—4.40 (m, 4H,
2CH2), 5.09—5.45 (m, 5H, CH, 2CH2), 5.73 (s, 1H,
CH), 5.94 (s, 1H, NH), 7.57 (s, 1H, CH), 7.62 (s, 1H,
CH); 13C NMR (100 MHz, CDCl3-TMS) δ: 13.95, 14.02,
18.78, 19.67, 22.39, 26.11, 26.32, 28.14, 30.21, 31.09,
36.61, 37.02, 44.78, 47.99, 49.16, 50.06, 50.50, 52.11,
－
1
1449, 1331, 1194, 1136, 960, 672 cm ; MS (ESI) m/z
(%): 812 ([M＋Na]＋, 95). Anal. calcd for C37H58Br-
N7O7: C 56.15, H 7.33, N 12.39; found C 56.34, H 7.38,
N 12.53.
(S)-Bis((1-hexyl-1H-1,2,3-triazol-4-yl)methyl)-2-
2416
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© 2012 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2012, 30, 2411—2422

Synthesis of 2(5H)-Furanone Derivatives with Bis-1,2,3-triazole Structure
58.43, 59.25, 77.31, 84.52, 97.68, 123.60, 123.88,
141.52, 141.95, 160.36, 167.54, 169.64, 169.80; IR
(CH2Cl2) ν: 3470, 3191, 2974, 2935, 2864, 1748, 1644,
result (Entry 4). Therefore, the temperature is controlled
at room temperature (25 ℃) in the following tests. The
reaction time also affects the reaction (Entries 2, 5 and
6), but it is possible to shorten the reaction time from 72
h to 48 h (Entry 5). When the reaction is carried out for
the same time (48 h), the influences of some common
alcohol solvents indicate that ethanol is still more effec-
tive than methanol (Entry 7).
－
1
1455, 1331, 1233, 1136, 952, 600 cm ; MS (ESI) m/z
＋
(%): 798 ([M ＋ Na]
, 85). Anal. calcd for
C36H54BrN7O7: C 55.62, H 6.95, N 12.62; found C
55.46, H 7.06, N 12.58.
Thus, when 1.0 mmol (5S)-5-bornyloxy-3,4-
dibromo-2(5H)-furanone 1c is reacted with 1.2 equiv.
Glu 2a, the optimized reaction conditions can be sum-
marized in the following: 25 ℃, 48 h, 3.5 equiv. KOH
as the base, and anhydrous EtOH as the solvent. Under
the above conditions, a series of N-[2(5H)-furanonyl]
amino acids derived from Glu 2a and Asp 2b are syn-
thesized (Table 2).
Compared with the results from monocarboxyl
amino acids,[18] it can be seen from Table 2 that dicar-
boxyl amino acids have an important influence on the
asymmetric Michael addtion-elimination reaction. The
existence of another carboxyl group not only reduces
the nucleophilicity of the amino, but also increases the
steric hindrance of the substrate. Both are disadvanta-
geous for the tandem reaction. Therefore, the yields
(22%—43%) are usually lower than those before.[18] On
the other hand, Asp 2b is more likely to get the products
with the higher yields than Glu 2a (e.g. Entries 4 vs. 1,
and 6 vs. 3). This might be related to the shorter chain
of Asp 2b, which is advantageous to lower the lipid
solubility of Asp 2b, and increase the solubility of its
mixture with potassium hydroxide in ethanol.
Results and Discussion
Syntheses of new intermediates N-[5-alkoxy-2(5H)-
furanonyl] amino acids 3
In our previous research, we have prepared N-[5-
alkoxy-2(5H)-furanonyl] amino acids[18] and their
propargyl esters[15f] starting from monocarboxyl amino
acids. Herein, in order to further combine bis-1,2,3-tri-
azole with 2(5H)-furanone moiety, we use bioactive
dicarboxyl amino acids (e.g. glutamic acid, Glu, 2a and
aspartic acid, Asp, 2b)[19] in place of monocarboxyl
amino acids[18] to synthesize new intermediates 3. The
investigations on the similar asymmetric Michael
addtion-elimination reaction show that the reaction con-
ditions, including the dosage of the base, the reaction
temperature and time, affect the reaction. Taking (5S)-5-
bornyloxy-3,4-dibromo-2(5H)-furanone 1c and Glu 2a
as the model substrates (Scheme 2), the results are
summarized in Table 1.
Scheme 2 The reaction of 1c and Glu 2a
O
O
Glutamic
acid
HO
OH
Br
2a
Br
H
Br
HN
KOH, solvent
Syntheses of new intermediates N-[5-alkoxy-2(5H)-
furanonyl] amino acid propargyl esters 4
H
24 - 72 h
25 - 50 oC
O
O
O
O
O
O
1c
3c
Usually, amino acid propargyl esters are synthesized
via condensation using N-protected amino acid and
propargyl alcohol as materials, and the reported syn-
thetic methods have many drawbacks.[15f,20,21] Only re-
cently, there are a few reports on the synthesis of amino
acid propargyl esters using N-protected amino acid and
propargyl bromide as materials.[15f,21] Due to the intro-
duction of dicarboxyl amino acids, we have to optimize
experimental conditions again according to the reported
before.[15f] Using the substitution reaction of N-
[5-bornyloxy-2(5H)-furanonyl] glutamic acid 3c with
propargyl bromide as an example (Scheme 3), the
reuslts are shown in Table 3.
Table 1 Condition optimization for the reaction of 1c with 2a
Entrya
KOH/mmolSolvent
Temp./℃ Time/h Yieldb/%
1
2
3
4
5
6
3.0
3.5
4.0
3.5
3.5
3.5
3.5
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
MeOH
25
25
25
50
25
25
25
72
72
72
72
48
24
48
19
32
29
28
32
25
7
28
a
b
Reaction conditions: 1c (1.0 mmol), 2a (1.2 equiv.). Isolated
The dosages of the base K2CO3 are first examined
(Table 3, Entries 1—4), and the results indicate that 4.0
mmol K2CO3 is the most effective, and the correspond-
ing yield of amino acid ester 4c is 41% (Entry 3). Once
reducing the base dosage, the reaction is slightly incom-
plete. The more base dosage may bring about the side-
reaction, and make the yield lowered (Entry 4). In fact,
the solvent has a bigger effect on the substitution reac-
tion (Entries 3 and 5—8), and DMSO is the best solvent
(Entry 8). Even in DMSO, the reaction time can be
yield.
Firstly, the investigation results of the dosages of the
base KOH (Table 1, Entries 1—3) indicate that 3.5
mmol KOH is the most effective (Entry 2). Once re-
ducing the base dosage, the yield is lowered obviously
(Entry 1). While excessive base may cause the side re-
action, which makes the yield lowered slightly (Entry 3).
When the dosage of the base KOH is kept unchanged,
increasing the reaction temperature does not give good
Chin. J. Chem. 2012, 30, 2411—2422
© 2012 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
www.cjc.wiley-vch.de
2417

Huo et al.
FULL PAPER
Table 2 Syntheses of different 2(5H)-furanone intermediates 3
Table 3 Condition optimization for the substitution reaction of
3c with propargyl bromide
Entrya
1
2
Products 3
Yieldb/%
Entrya
K2CO3/mmol
Solvent Time/h
Yieldb/%
O
O
1
2
2.0
3.0
4.0
4.5
4.0
4.0
4.0
4.0
4.0
4.0
4.0
CH3CN
CH3CN
CH3CN
CH3CN
EtOH
24
24
24
24
24
24
24
24
12
8
25
HO
OH
Cl
31
HN
1
22
1a 2a
3
41
H
O 3a
O
O
4
40
O
5
0
O
6
CH2Cl2
DMF
40
HO
OH
Br
7
49
HN
2
3
4
5
6
38
32
40
33
43
1b 2a
8
DMSO
DMSO
DMSO
DMSO
62
H
9
62
O 3b
O
O
O
10
11
54
4
39
O
a
Reaction conditions: 2(5H)-furanone intermediate 3c (1.0
mmol), propargyl bromide (2.5 equiv.). b Isolated yield.
HO
OH
Br
HN
1c
2a
H
Thus, when choosing 1.0 mmol N-[5-bornyloxy-
2(5H)-furanonyl] glutamic acid 3c and 2.5 mmol
propargyl bromide as the model substrates, the opti-
mized reaction conditions can be summarized in the
following: 40 ℃, 12 h, 4.0 mmol K2CO3 as the base,
and anhydrous DMSO as the solvent. Under the opti-
mized conditions, the substitution of a series of N-
[2(5H)-furanonyl] amino acids derived from Glu 2a and
Asp 2b are examined, and six new N-[5-alkoxy-2(5H)-
furanonyl] amino acid propargyl esters 4 are obtained
with the yields of 28%—70% (Table 4).
O 3c
O
O
O
HO
OH
Cl
O
HN
1a 2b
1b 2b
1c 2b
H
O 3d
O
O
O
HO
OH
Br
O
HN
H
Table 4 Syntheses of different 2(5H)-furanone intermediates 4
Entrya
Products 4
Yieldb/%
O3e
O
O
3
O
O
O
O
HO
O
O
OH
Br
O
HN
Cl
HN
1
28
3a
H
H
O
O 3f
O
O
O
4a
a
Reaction conditions: 2(5H)-furanone material 1 (1.0 mmol),
amino acid 2 (1.2 equiv.), 25 ℃, 48 h, 3.5 equiv. KOH as the
base, and anhydrous EtOH as the solvent. b Isolated yield.
O
O
O
O
Br
HN
Scheme 3 The reaction of 3c with propargyl bromide
2
70
3b
H
O
O
O
O
O
O
O
O
Br
K2CO3
4b
HO
OH
Br
O
O
HN
HN
Solvent
4 - 24 h
40 oC
Br
O
H
H
O
O
Br
O
O
O
O
O
O
HN
4c
3c
3
62
3c
H
O
O
shortened from 24 to 12 h (Entry 9). However, the rela-
tively less time is obviously disadvantageous for the
reaction (Entries 10 and 11).
O
4c
2418
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© 2012 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2012, 30, 2411—2422

Synthesis of 2(5H)-Furanone Derivatives with Bis-1,2,3-triazole Structure
Continued
Scheme 4 Reaction of 4c with benzyl azide 5a
Entrya
Products 4
Yieldb/%
3
N
N
N
N
N
N
O
OOC
COO
Br
Ph
Ph
2
O
O
Benzyl azide
5a
H
HN
O
O
O
HN
Cl
4
43
3d
H
4c
H
Catalyst
Solvent, r.t.
O
O
O
O
O
O
O
6ac
4d
Table 5 Condition optimization for the click reaction of 4c with
benzyl azide 5a
O
O
Br
Entrya Catalyst system
Solvent Time/h Yieldd/%
HN
5
69
3e
1
CuBr
CH3CN 48
CH3CN 48
CH3CN 48
CH3CN 48
12
39
54
50
0
H
2b
CuSO4•5H2O/SA
CuSO4•5H2O/Cu
CuSO4•5H2O/Cu
CuSO4•5H2O/Cu
CuSO4•5H2O/Cu
CuSO4•5H2O/Cu
CuSO4•5H2O/Cu
CuSO4•5H2O/Cu
CuSO4•5H2O/Cu
O
O
O
O
3
4e
4c
5
EtOH
CH2Cl2 48
DMF 48
48
O
6
37
44
50
39
53
O
Br
7
HN
6
55
3f
H
8
DMSO 48
CH3CN 24
CH3CN 72
O
O
9
O
10
4f
a
Reaction conditions: 2(5H)-furanone intermediate 4c (1.0
a Reaction conditions: 2(5H)-furanone intermediate 3 (1.0 mmol),
propargyl bromide (2.5 equiv.), 40 ℃, 12 h, 4.0 mmol K2CO3 as
the base, and anhydrous DMSO as the solvent. b Isolated yield.
mmol), benzyl azide 5a (2.0 equiv.), catalyst (CuI 0.2 equiv.,
b
except for special explanations). Sodium ascorbate (SA, 0.2
equiv.) was used instead of Cu. c CuSO4•5H2O (0.05 equiv.), Cu
(0.1 equiv.). d Isolated yield.
On one hand, it can be seen from Table 4 that dif-
ferent halogen atoms in 2(5H)-furanone intermediates 3
may have an effect on the reaction, and the yields of the
products 4 containing chlorine atom are relatively lower
(Entries 1 and 4). This may be related to the stronger
electronegativity value of chlorine atom, which will lead
to the formation of the hydrogen bond between the car-
boxyl in amino acid and chlorine atom, and further hin-
dering the expected substitution reaction. On the other
hand, different 5-substituents in 2(5H)-furanone inter-
mediates 3 also have an influence on the reaction, and
usually the intermediates 3 with 5-menthoxy group give
the products 4 with the higher yield than that with
5-bornyloxy group (Entries 2 vs. 3, and 5 vs. 6). Perhaps
the less steric hindrance of 5-menthoxy group than that
of 5-borneoxy group makes the reaction proceed more
smoothly.
is obtained (Entry 3). If the catalytic system is replaced
by CuBr (Entry 1) or CuSO4•5H2O/sodium ascorbate
(Entry 2), some by-products can be detected according
to the TLC monitoring, and the yield also drops. Fur-
thermore, if decreasing the dosage of catalysts into the
half, the yield becomes lower (Entry 4). Thus, the suit-
able catalyst system should be 0.1 mmol CuSO4•5H2O
and 0.2 mmol Cu.
The solvent also affects the reaction significantly
(Table 5, Entries 5—8). For example, in EtOH, the re-
action does not take place. Similarly, changing other
solvents while maintaining the same reaction time (48
h), the results indicate that CH3CN is the best of all
(Entry 3). However, once the reaction time is shortened
(Entry 9) or lengthened (Entry 10), the yield is not satis-
fied. Therefore, when choosing 1.0 mmol 4c and 2.0
equiv. benzyl azide 5a as the model substrates, the op-
timized reaction conditions can be summarized in the
following: CH3CN as the solvent, 0.1 equiv. CuSO4•
5H2O and 0.2 equiv. Cu as the catalytic system, room
temperature for 48 h.
Syntheses of target compounds bis-1,2,3-triazoles 6
Based on the above syntheses of the intermediates 3
and 4, the preparations of the target compounds 6 are
investigated. Choosing N-[5-bornyloxy-2(5H)-furanonyl]
glutamic acid propargyl ester 4c and benzyl azide 5a as
the model substrates of the click reaction (Scheme 4),
the experimental conditions are optimized (Table 5).
The influences of different catalysts are evaluated
first (Table 5, Entries 1—3). Obviously, when using
CuSO4•5H2O/Cu as catalytic system, a satisfactory yield
Under these conditions, changing substrates, more
new 2(5H)-furanone derivatives 6 containing bis-1,2,3-
triazole moiety are designed and successfully synthe-
sized with the yields of 48%—69% (Table 6). It can be
seen that, though the side-reactions, especially Glasser
coupling reaction of diyne,[22] maybe occur, the click
Chin. J. Chem. 2012, 30, 2411—2422
© 2012 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
www.cjc.wiley-vch.de
2419

Huo et al.
FULL PAPER
reaction proceeds smoothly whether the main chain of
amino acid is long or short, and whether the side chain
in azidoalkanes is hexyl or benzyl.
Continued
Yieldb/%
Entrya
4
5
Target compounds 6
O
O
However, different intermediate N-[5-alkoxy-2(5H)-
furanonyl] amino acid propargyl ester 4 has some in-
fluences. For example, when 5-substituent in 2(5H)-
furanones 4 is different, 5-menthoxy with less steric
hinderance generally results in a higher yield than
5-bornyloxy (Table 6, Entries 2 vs. 3, 5 vs. 6, and 8 vs.
9).
N
N
N
N
O
O
N
N
HN
Cl
7
66
4a 5b
H
O
O
O
O
6ba
Table 6 Syntheses of different bis-1,2,3-triazoles 6
O
N
N
Entrya
4
5
Target compounds 6
Yieldb/%
N
N
O
O
N
N
HN
O
O
Br
8
9
59
56
66
4b 5b
4c 5b
4d 5b
N
N
N
N
H
O
O
O
O
N
N
N
N
N
N
O
O
O
O
HN
Cl
1
66
4a 5a
Ph
6bb
H
Ph
O
O
O
O
O
N
N
O
O
6aa
N
N
N
N
HN
Br
O
H
N
N
N
N
O
Br
O
O
O
HN
6bc
2
3
4
63
54
52
4b 5a
4c 5a
4d 5a
Ph
H
Ph
O
O
O
O
N
N
N
N
O
O
O
N
N
N
N
O
6ab
HN
Cl
10
O
H
N
N
N
N
O
O
O
O
Br
O
HN
6bd
Ph
H
Ph
O
O
O
N
N
N
N
O
6ac
O
N
O
O
HN
Br
11
48
4e 5b
N
N
N
O
H
O
N
N
N
O
O
O
O
O
HN
Cl
6be
Ph
Ph
H
O
O
O
O
N
N
N
N
6ad
O
O
N
O
HN
Br
12
67
4f 5b
N
N
N
N
O
H
O
N
N
O
O
O
O
HN
Br
5
69
4e 5a
6bf
Ph
Ph
H
a Reaction conditions: 2(5H)-furanone intermediate 4 (1.0 mmol),
azidoalkane 5 (2.0 equiv.), CH3CN as the solvent, 0.1 equiv.
CuSO4•5H2O and 0.2 equiv. Cu as the catalytic system, room
temperature for 48 h. b Isolated yield.
O
O
O
O
6ae
N
N
N
N
O
O
N
N
O
HN
Br
What’s more, it can be seen that 3-chloro-2(5H)-
furanone intermediates 4 usually give the higher yields
than 3-bromo-2(5H)-furanones (Table 6, Entries 1 vs. 2,
7 vs. 8, and 10 vs. 11). This may be related to the reac-
tion mechanism of click reaction.[23] Because chlorine
6
59
4f 5a
Ph
Ph
H
O
O
O
6af
2420
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© 2012 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2012, 30, 2411—2422

Synthesis of 2(5H)-Furanone Derivatives with Bis-1,2,3-triazole Structure
atom has bigger electronegativity value than bromine
atom, it is more likely to attract the hydrogen atom of
terminal alkyne, which makes the leave of hydrogen
atom more easier and promotes the click reaction.
Acknowledgement
We are grateful to the National Natural Science
Foundation of China (No. 20772035), the Third Talents
Special Funds of Guangdong Higher Education (No.
Guangdong-Finance-Education [2011]431) and the
Natural Science Foundation of Guangdong Province
(No. S2011010001556) for financial support.
Structure characterization of all new compounds
All new chiral 2(5H)-furanone compounds are sys-
tematically characterized. In the following discussions,
we choose the characterizations of target compounds 6
as examples.
References
In the IR spectra, the N—H groups show stretching
absorption in the region of 3350—3490 cm-1, while un-
saturated C—H groups of aromatic rings or triazole
rings show stretching absorption in the region of 3030—
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－
1
3200 cm . At the same time, the strong C＝O stretch-
－
1
ing band appears at 1740—1755 cm , and the C＝C
stretching band occurs in 1634—1664 cm－1 region. Be-
sides, skeletal stretching vibrations of aromatic rings or
triazole rings absorb in the region of 1450—1570
－
1
cm .
In the UV spectra, for most compounds, there are
strong absorption peaks in the region of 261—274 nm
caused by π→π* transition of C＝C—C＝O conjugated
system in 2(5H)-furanone ring.
In 1H NMR, there is a singlet peak in the region of δ
5.61—5.74, which is the characteristic peak of 5-H in
2(5H)-furanone. Furthermore, there is a singlet peak in
the region of δ 7.50—7.63 for the proton of bis-
1,2,3-triazoles 6. In a word, the structures of all newly
synthesized compounds are right as expected.
In our previous research,[16c] it has been proved that
different 2(5H)-furanone derivatives containing mono-
1,2,3-triazole moiety could be synthesized from avail-
able 5-alkoxy-3,4-dihalo-2(5H)-furanones, amino acids,
propargyl bromide and azidoalkanes through Michael
addition-elimination, substitution and cycloaddition via
a simple and efficient multi-component one-pot ap-
proach. Therefore, it is also possible to get bis-1,2,3-
triazoles 6 by the similar way.
Conclusions
In summary, using dicarboxyl amino acids as new
building blocks, a series of new chiral 2(5H)-furanone
derivatives containing bis-1,2,3-triazole moiety are de-
signed and synthesized under mild conditions via three
sequential steps, such as asymmetric Michael addi-
tion-elimination, substitution and no-ligand click reac-
tion in this research. Meanwhile, those new compounds,
1
including intermediates, are characterized by FTIR, H
NMR, 13C NMR, MS and elemental analysis. The re-
search provides a new method and idea for the synthesis
of 2(5H)-furanone compounds with polyheterocyclic
structure. Due to the diversities of four basic unit mole-
cules, it also provides a theoretical and practical basis
for further bioactive investigations.
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Huo et al.
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(Lu, Y.)
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Chin. J. Chem. 2012, 30, 2411—2422