The synthesis of some new (S)-1-aryl-N-(1-hydroxy-3-phenylpropan-2-yl)-5- methyl-1H-1,2,3-triazole-4-carboxamide

Article abstract of DOI:10.1002/jhet.1567

Some new (S)-1-aryl-N-(1-hydroxy-3-phenylpropan-2-yl)-5-methyl-1 H-1,2,3-triazole-4-carboxamides 4a, 4b, 4c, 4d, 4e, 4f, 4g, 4h, 4i, 4j have been synthesized and established by ¹H and ¹³C NMR, IR, MS spectra, CHN analyses, and x-ray

Full text of DOI:10.1002/jhet.1567

Month 2013 The Synthesis of Some New (S)-1-Aryl-N-(1-hydroxy-3-phenylpropan-2-yl)-
5-methyl-1H-1,2,3-triazole-4-carboxamide
*
G.-L. Shen, Z.-B. Chen, Z.-F. Wu, and H.-S. Dong
State Key Laboratory of Applied Organic Chemistry, Institute of Organic Chemistry, College of Chemistry and Chemical
Engineering, Lanzhou University, Lanzhou, Gansu 730000, People’s Republic of China
*
E-mail: donghengshan@lzu.edu.cn
Received June 14, 2011
DOI 10.1002/jhet.1567
Published online 00 Month 2013 in Wiley Online Library (wileyonlinelibrary.com).
1), HCl, NaNO2,0-5°C
2), NaN3,0-5°C
NH2
R
H2C
O
H3C
3), CH3COCH2COOEt,EtONa, EtOH
N
H
H
CH2
4)SOCl2
N
N
N
5)CH2Cl2,Et3N,(S)-2-amino-
3-phenylpropan-1-ol
O
R
H
4a-j
Some new (S)-1-aryl-N-(1-hydroxy-3-phenylpropan-2-yl)-5-methyl-1 H-1,2,3-triazole-4-carboxamides 4a–j
have been synthesized and established by 1H and 13C NMR, IR, MS spectra, CHN analyses, and x-ray
diffraction crystallography. The molecular conformation and packing is stabilized by interactions of intermolecular
H-bond O2’-H2’···O1, O2-H2···O1’ and intramolecular H-bond N4’-H4’N···N3’, N4’-H4’N···O2’, N4-
H4N···N3, N4-H4N···O2. The two rings of five numbers were formed by H-bond in a molecular.
J. Heterocyclic Chem., 00, 00 (2013).
INTRODUCTION
Identified as a compound, IR absorption of hydroxyl is
showing at 3359 ~ 3478 cm-1 and amino at 3201 ~ 3416 cm-1
of 4a–j, as a carbonyl compound showing strong IR
absorption at 1642 ~ 1661 cm-1. 1HNMR, chemical shift range
of triazole-5-CH3 peak is at 2.464 ~ 2.647 ppm of 4a–i and
chemical shift range of -CO-NH- doublet peaks is show at
7.507 ~ 8.594 ppm, J= 8.0 ~ 8.8 Hz of 4a ~ j, which are shifted
to lower fields than the corresponding protons at 6.29 ppm
[11] because of the hydrogen-bond and triazole ring
induced. The chemical shift range of CH2Ph peak is at
2.854 ~ 3.067 ppm, chemical shift range of CH2O doublet
peaks is show at 2.854 ~ 3.747 ppm, 2.958 ~ 3.849 ppm,
chemical shift range of CHN peak is at 4.199 ~ 4.463ppm of
4a ~ i. 13CNMR, chemical shift range of triazole-5-CH3 peak
is at 9.29–10.34 ppm and chemical shift range of –CO- peaks
is show at 161.02 ~ 162.08 ppm of 4a ~ i.
The (S)-2-amino-3-phenylpropan-1-ol, a surprising con-
stituent was the peptide derivative, acid amide previously
found in many natural products [1–3]. In recent years in
various publications, certain compounds that 1-aryl-5-
methyl-4-substituted-1,2,3-triazoles often exhibit broad
spectrum biological actions [4,5], antibacterial [6], antifungal
[7], antiviral [8], anti-inflammatory, and analgetic properties
[9]. Some of 1,2,3-triazole derivatives had been reported to
inhibit tumor proliferation, invasion, and metastasis [10].
Therefore, it is worthwhile to investigate these properties of
1,2,3-triazole. As a great deal of interest has been focused on
it, we synthesized some new title compound.
The route of syntheses of the title compound is in
Scheme 1.
An ORTEP diagram of the compound 4e showing
50% thermal ellipsoids is shown in Figure 1. The X-ray
structure analysis indicated that the compound 4e consisted
of two phenyl rings and one triazole ring. The p-chlorophenyl
ring and a triazole ring do not share a common plane. The
dihedral angles between the phenyl rings and triazole rings
are 39.9–45.2ꢀ [C5-C6-N1-N2 -45.2(6)ꢀ, C1’-C6’-N1’-N2’
39.9(6)ꢀ].
RESULTS AND DISCUSSION
Title compound was obtained by the reaction of a chiral
(S)-2-amino-3-phenylpropan-1-ol, triethylamine and 1-aryl-
5-methyl-1,2,3-triazol-4-carboxylic acid acyl chloride in
dichloromethane, which was from reaction of triazole
carboxylic acid was treated with thionyl chloride in
dichloromethane.
Our own interest in the development of some new (S)-1-
aryl-N-(-1-hydroxy-3-phenylpropan-2-yl)-5-methyl-1H-1,2,
3-triazole-4-carboxamides and in extending this type
of one-pot reaction prompted us to examine potential
applications and generalizations to the synthesis of
substituted derivatives.
In the crystal structure, there are two intermolecular
O2’-H2’···O1, O2-H2···O1’ hydrogen bond involving the
hydroxyl group O-H bond and other molecular carbonyl
group O. The bond length of Donor-H···Acceptor is 2.76 Å
(O2’-H2’ 0.82; H2’···O1 1.97 Å) and 2.71 Å (O2-H2 0.82;
H2···O1’ 2.00 Å), the bond angle is 162 and 143ꢀ. There are
© 2013 HeteroCorporation

G.-L. Shen, Z.-B. Chen, Z.-F. Wu, and H.-S. Dong
Vol 000
Scheme 1. The synthesis route of compounds 4a–j.
EXPERIMENTAL
The melting point was uncorrected and determined on an XT4-100x
microscopic melting point apparatus. IR spectra were obtained in KBr
discs on a Shimadzu (American Pyroelectricity Corporation, USA)
IR-435 spectrometer. MS was performed on a TRACED SQ instru-
ment (EI at 70eV). 1 H NMR and 13 C NMR spectroscopy (CDCl3)
was recorded on Varian Mercury-400BB instrument H1 in
400.1370316 and C13 in 100.6127476 MHz with TMS as an
internal standard. Elemental analyses were carried out on a
Yanaco CHN Corder MT-3 analyzer. Optical rotatory power
values were measured with an A21202-Tapiv automatic polarim-
eter at sodium D line 589 nm.
Preparation of the title compound. General procedure for
the preparation of 1-aryl-5-methyl-1,2,3-triazol-4-carboxylic
acid (3a–j).
1-Aryl-5-methyl-1,2,3-triazol-4-carboxylic acid
3a–j was prepared following methods in the literature [12].
General procedure for the preparation of (S)-1-aryl-N-
(1-hydroxy-3-phenylpropan-2-yl)-5-methyl-1 H-1,2,3-triazole-4-
carboxamide (4a–j). (S)-1-Aryl-N-(1-hydroxy-3-phenylpropan-
2-yl)-5-methyl-1 H-1,2,3-triazole-4-carboxamide 4a–j was prepared
following methods in the literature [13].
The 1-aryl-5-methyl-1,2,3-triazol-4-carboxylic acid 3a–j
(10.0 mmol) was treated with thionyl chloride (5 mL), then heated
at 70ꢀC for 8 h. The excess thionyl chloride was removed by
evaporation under reduced pressure. Residual thionyl chloride
was removed by co-evaporation with 30 mL of anhydrous
benzene to afford the corresponding acid chloride.
To a cold (À5–0ꢀC) solution of a chiral (S)-2-amino-3-
phenylpropan-1-ol (1.51 mg, 10.0 mmol) and a solution of
triethylamine (2.52 g, 25.0 mmol) in 20 mL of dichloro-
four intramolecular N4’-H4’N···N3’, N4’-H4’N···O2’,
N4-H4N···N3, and N4-H4N···O2. Hydrogen bond involving
the N-H bond and triazole ring 3 positions N or hydroxyl
group O. The bond length of Donor-H···Acceptor is
2.75 Å (N4’-H 0.93; H···N3’ 2.36Å), 2.67 Å (N4’-H 0.93;
H···O2’ 2.26Å), 2.79Å (N4-H 0.89; H···N3 2.46Å),
and 2.61Å (N4-H 0.89; H···O2 2.16Å); the bond angle
is 105, 106, 103 and 111ꢀ. The molecular conforma-
tion and packing is stabilized by interactions of two
intermolecular and four intramolecular. The two rings
of five numbers were formed by H-bond in a molecu-
lar. The H-bond structure of the compound 4e is
shown in Figure 2.
methane,
a
solution of 1-aryl-5-methyl-1,2,3-triazol-4-
carboxylic acid acyl chloride (2.50 g, 9.8 mmol) in 30 mL
dry dichloromethane over a period of 40 min was added.
The reaction mixture was stirred at 0ꢀC for 5 h and then
at 25ꢀC for 4 h. The product precipitated from the solution
was collected by filtration, then washed with 1 M HCl
(30 mL), saturated aqueous NaHCO3 (30 mL), and distilled
water. The crude product was either purified by recrystalli-
zation from EtOH or by column chromatography with silica
gel as adsorbent and ethyl acetate/petroleum ether (1:2
volume ratios) as the eluent. The title compound 4a–j
was obtained.
Figure 1. ORTEP diagram of the compound 4e showing 50% thermal ellipsoids. [Color figure can be viewed in the online issue, which is available at
wileyonlinelibrary.com.]
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2013
(S)-N-(-1-hydroxy-3- phenylpropan-2-yl)-1,2,3- triazole carboxamide
Figure 2. The H-bond structure of the compound 4e (PWT drawing for the Platon). [Color figure can be viewed in the online issue, which is available at
wileyonlinelibrary.com.]
Table 2
The purified product was dissolved in ethyl acetate and petroleum
ether solvent. The crystal was obtained after 20d by evaporation of the
Selected bond angles (º) and dihedral angle (º).
solvent.
Atoms Angle
Atoms Angle
Single crystals were selected and mounted on the tip of a glass
fiber. Data were collected on a SMART APEX II CCD using
graphite monochromatized MoKa radiation (l = 0.71073 Å). The
structure was determined by direct methods (SHELXS-97) and
refined by full covariance matrix methods (SHELXL-97). The
structure of the title compound is shown in Figure 1. The selected
bond lengths are given in Table 1. The selected bond angles are
given in Table 2. Hydrogen bonds (Angstrom, Deg) are given
in Table 3. The geometric calculations were performed using
the program SHELX-97.
C2 C3 Cl1 119.4(4)
C4 C3 Cl1 119.5(4)
C1 C6 N1 120.2(4)
C5 C6 N1 118.7(4)
N1 C7 C8 103.4(4)
N1 C7 C18 124.5(4)
C8 C7 C18 132.2(4)
N3 C8 C7 109.7(4)
N3 C8 C9 122.6(4)
C7 C8 C9 127.7(4)
O1 C9 N4 123.0(5)
O1 C9 C8 121.1(4)
N4 C9 C8 115.9(4)
N4 C10 C19 106.6(4)
N4 C10 C11 111.8(4)
C19 C10 C11 113.4(5)
C12 C11 C10 111.7(4)
O2 C19 C10 107.9(5)
C1 C2 C3 Cl1 179.9(4)
C18 C7 C8 N3 -178.5(5)
N3 C8 C9 O1 174.1(5)
N3 C8 C9 N4 -4.6(7)
N4 C10 C11 C12 -159.7(4)
C19 C10 C11 C12 79.8(6)
N4 C10 C19 O2 -46.3(6)
C5 C6 N1 N2 -45.2(6)
C1’ C2’ C3’ Cl1’ 179.0(4)
C18’ C7’ C8’ N3’ 174.7(5)
N3’ C8’ C9’ O1’ 167.8(6)
N3’ C8’ C9’ N4’ -9.7(7)
N4’ C10’ C11’ C12’ 170.7(4)
C19’ C10’ C11’ C12’ 49.3(6)
N4’ C10’ C19’ O2’ -57.8(6)
C1’ C6’ N1’ N2’ 39.9(6)
(S)-1-(3-Bromophenyl)-N-(1-hydroxy-3-phenylpropan-2-
yl)-5-methyl-1H-1,2,3-triazole-4-carboxamide (4a).Yield: 65%;
white needle crystals; mp 115–117ꢀC; [a]D17.7 = À42.453
Table 1
Selected bond lengths (Å).
Atoms length
Atoms length
C3 Cl-1 1.737(4)
C6 N1 1.427(5)
C7 N1 1.363(5)
C7 C8 1.368(6)
C7 C18 1.481(6)
C8 N3 1.364(6)
C8 C9 1.487(6)
C9 O1 1.241(5)
C9 N4 1.304(6)
C10 N4 1.478(5)
C10 C19 1.516(6)
C10 C11 1.535(7)
C11 C12 1.516(6)
C19 O2 1.410(7)
C3’ Cl1’ 1.720(5)
C6’ N1’ 1.440(5)
C7’ N1’ 1.352(5)
C7’ C8’ 1.377(6)
C7’ C18’ 1.466(6)
C8’ N3’ 1.352(5)
C8’ C9’ 1.484(6)
C9’ O1’ 1.224(5)
C9’ N4’ 1.327(6)
C10’ N4’ 1.448(5)
C10’ C19’ 1.499(7)
C10’ C11’ 1.529(8)
C11’ C12’ 1.506(7)
C19’ O2’ 1.348(5)
Table 3
Hydrogen bonds (Å, º).
D
H
A
DH
HA
DA
DHA
O2’
N4’
N4’
O2
N4
N4
H2’
O1
0.8200
1.9700
2.762(6) 162.00
2.671(6)
2.754(5)
2.706(6) 143.00
2.607(7)
2.794(5)
H4’N
H4’N
H2
H4N
H4N
O2’
N3’
O1’
O2
0.93(4) 2.26(4)
0.93(4) 2.36(4)
106(3)
105(3)
0.8200
2.0000
0.89(4) 2.16(4)
0.89(4) 2.46(4)
111(3)
103(3)
N3
2-x,1/2 + y,1-z; 1-x,-1/2 + y,1-z
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

G.-L. Shen, Z.-B. Chen, Z.-F. Wu, and H.-S. Dong
Vol 000
(c = 10.6 mg/mL, CHCl3); 1HNMR (d ppm, CDCl3): 2.611(s,3H),
2.997–3.022(dd, 2H, J = 2.8, 7.2 Hz; b, 1H, -OH), 3.685–3.726
(dd, 1H, J = 5.4, 11.0 Hz), 3.790–3.827(dd, 1H, J = 3.6, 11.2 Hz),
4.355–4.394(m, 1H), 7.200–7.257(b, 1H, N-H), 7.280–7.328
(m, 4H, J = 2.0, 8.0 Hz), 7.427–7.467(t, 2H, J = 8.0
Hz), 7.512–7.532(d, 1H, J = 8.0 Hz), 7.625–7.634(t, 1H, J = 1.8
Hz), 7.679–7.699(d, 1H, J = 8.0 Hz, CO-NH); 13CHNR
(d ppm, CDCl3): 9.95, 37.49, 53.11, 64.41, 123.33, 123.97,
126.84, 128.58, 128.85, 129.49, 131.08, 133.34, 136.75, 137.07,
137.82, 138.65, 161.74; MS M/z (%): 414 (M+, 0.4) 416
(M + 2, 0.4), 385(2), 383(1), 355(1), 341(1), 325(6), 323(6),
307(2), 305(3), 295(3), 297(3), 281(3), 262(3), 247(4), 238
(5), 236(7), 223(7), 219(6), 210(6), 209(8), 208(7), 207(12), 205
(8), 191(9), 178(12), 165(13), 152(17), 151(17), 149(39), 138
(19), 129(29), 125(20), 124(26), 123(23), 111(34), 110(23), 105
(23), 97(48), 91(41), 84(76), 71(49), 69(59), 64(79), 57(100), 55
(84); IR(KBr, cm-1): 543.0, 572.8, 681.1, 705.1, 754.8, 785.2,
864.9, 1044.3, 1074.7, 1143.8, 1263.0, 1429.4, 1460.3, 1490.0,
1512.5, 1590.2, 1661.5, 2869.8, 2931.6, 3022.6, 3083.6, 3393.5,
3478.2. Anal. Calcd. for C19H19BrN4O2: C, 54.95; H, 4.61; N,
13.49; Found: C, 55.06; H, 4.65; N,13.32.
577.9, 660.0, 701.2, 746.1, 764.5, 851.9, 914.4, 1030.9, 1074.1,
1145.3, 1264.2, 1447.2, 1494.7, 1515.0, 1586.5, 1641.5, 2881.2,
2926.3, 3032.1, 3065.8, 3086.6, 3279.4, 3358.8. Anal. Calcd. for
C19H19ClN4O2: C, 61.54; H, 5.16; N, 15.11; Found: C, 61.46; H,
5.21; N, 15.20.
(S)-1-(3-Chlorophenyl)-N-(1-hydroxy-3-phenylpropan-2-
yl)-5-methyl-1H-1,2,3-triazole-4-carboxamide (4d).
Yield:
41%; white needle crystals; mp 95–97ꢀC; [a]D17.5 = À47.664
(c= 10.7mg/mL, CHCl3); 1HNMR (d ppm, CDCl3): 2.613
(s, 3H), 2.964–3.058(dd, 2H, J = 3.2, 7.2 Hz; b, 1H, -OH),
3.686–3.728(dd, 1H, J = 5.6, 11.2 Hz), 3.791–3.828
(dd, 1H, J = 3.6, 11.2 Hz), 4.357–4.437(m, 1H), 7.199–7.255
(b, 1H, N-H), 7.281–7.308(m, 5H, J = 2.0, 8.0 Hz), 7.472–7.487
(dd, 1H, J = 1.6, 3.2 Hz), 7.507–7.533(m, 3H, Ar-H, CO-NH);
13CHNR (d ppm): 9.96, 37.49, 53.10, 64.41, 123.51, 125.73,
126.83, 128.84, 129.49, 130.41, 130.87, 135.67, 136.66, 137.06,
137.82, 138.66, 161.74; MS M/z (%): 370 (M+, 0.52) 372
(M+ 2, 0.14), 349(3), 341(6), 339(14), 289(40), 281(32), 279
(100), 271(5), 261(9), 237(7), 222(10), 220(29), 202(12), 194
(11), 192(26), 174(11), 166(15), 164(32), 154(20), 152(47), 149
(33), 146(11), 128(12), 113(10), 111(26), 105(9), 91(28), 83
(10), 71(11), 57(17), 43(22). IR(KBr, cm-1): 551.8, 642.9,
682.4, 700.9, 745.0, 782.6, 868.2, 1035.3, 1075.6, 1145.2,
1268.0, 1425.1, 1492.7, 1524.8, 1586.8, 1648.5, 2928.2,
2947.1, 3023.8, 3056.9, 3080.3, 3304.9, 3412.4. Anal.
Calcd. for C19H19ClN4O2: C, 61.54; H, 5.16; N, 15.11;
Found: C, 61.43; H, 5.11; N, 15.02.
(S)-1-(4-Bromophenyl)-N-(1-hydroxy-3-phenylpropan-2-yl)-5-
methyl-1H-1,2,3-triazole-4-carboxamide (4b).
Yield: 85%;
white flaky crystals; mp 137–139ꢀC; [a]D16.8 = À46.535
(c = 10.1 mg/mL, CHCl3); 1HNMR (d ppm, CDCl3): 2.611
(s, 3H), 2.956–3.051(dd, 2H, J = 3.2, 7.2 Hz; b, 1H, -OH),
3.678–3.720(dd, 1H, J = 5.6, 11.0 Hz), 3.785–3.822(dd, 1H,
J = 3.6, 11.2 Hz), 4.354–4.433(m, 1H), 7.197–7.239(m, 1H,
N-H), 7.290–7.333(m, 6H), 7.526–7.546(d, 1H, J = 8.0 Hz),
7.691–7.713(d, 2H, J = 8.8 Hz); 13CHNR(d ppm, CDCl3):
9.94; 37.46; 53.07; 64.35; 124.38; 126.82; 126.86; 128.83;
129.48; 133.12; 134.64; 136.99; 137.82; 138.66; 161.74;
MS M/z (%): 414 (M+, 0.36) 416 (M + 2, 0.33), 385
(12), 383(13), 355(1), 325(93), 323(100), 307(5), 305(6),
289(2), 283(6), 281(7), 266(22), 264(25), 245(19), 243(26),
238(20), 236(19), 223(5), 210(17), 208(14), 198(44), 196
(40), 185(6), 157(76), 155(14), 149(31), 139(19), 129(39),
113(25), 111(66), 102(11), 91(36), 83(10), 75(20), 70
(14), 57(17), 55(14), 43(45), 40(54); IR(KBr, cm-1):
597.7, 620.6, 697.1, 744.0, 816.1, 840.0, 980.9, 1002.7,
1041.7, 1067.1, 1135.8, 1246.3, 1281.8, 1398.4, 1426.9,
1449.5, 1494.3, 1513.1, 1572.2, 1589.6, 1658.2, 2920.6,
2952.7, 2989.2, 3023.9, 3061.3, 3390.1, 3395.2. Anal. Calcd.
for C19H19BrN4O2: C, 54.95; H, 4.61; N, 13.49; Found: C,
54.86; H, 4.65; N, 13.55.
(S)-1-(4-Chlorophenyl)-N-(1-hydroxy-3-phenylpropan-2-
yl)-5-methyl-1H-1,2,3-triazole-4-carboxamide (4e). Yield:
80%; white flaky crystals; mp 138–139ꢀC; [a]D16.5 = À44.231ꢀ
(c = 0.1, CHCl3); 1 H NMR d(ppm, CDCl3): 2.576 (s, 3H,
CH3), 2.991–3.015 (dd, 2H, J = 2.4, 7.2 Hz, Ph-CH2-), 3.326
(b, 1H, OH), 3.675–3.716 (dd, 1H, J= 5.2, 11.0 Hz, -CH2O-),
3.780–3.816 (dd, 1H, J = 3.6, 11.2 Hz, -CH2O-), 4.359–4.438
(m, 1H, -CH-), 7.186–7.239 (m, 1H, -Ph-H), 7.284–7.294
(m, 4H, -Ph-H), 7.369–7.391 (d, 2H, J = 8.8 Hz, -C6H4-),
7.525–7.547 (d, 2H, J=8.8 Hz, -C6H4-), 7.554–7.574 (d, 1H,
J= 8 Hz, -CO-NH-); 13 C NMR d(ppm, CDCl3): 9.66, 37.21, 52.75,
63.91, 126.39, 126.52, 128.54, 129.24, 129.86, 133.87, 136.08,
136.78, 137.63, 138.38, 161.44. MS M/z (%): 370 (M+, 2) 372
(M + 2, 0.65), 348(25), 271(100), 257(16), 244(10), 228(14), 221
(32), 195(66), 165(34), 149(28), 115(20), 105(60), 91(14), 77
(41), 43(74). IR(KBr, cm-1): 533.0, 596.3, 694.7, 738.2, 835.0,
981.8, 1005.2, 1040.1, 1093.3, 1114.6, 1200.5, 1269.5, 1407.1,
1502.0, 1576.5, 1593.5, 1638.9, 1660.3(C= O), 2923.1, 2952.2,
3064.2, 3099.0, 3368.5(N-H), 3416.0(OH). Anal. Calcd. for
C19H19ClN4O2: C, 61.54; H, 5.16; N, 15.11; Found: C, 61.59;
H, 5.13; N, 15.20.
(S)-1-(2-Chlorophenyl)-N-(1-hydroxy-3-phenylpropan-2-yl)-5-
methyl-1H-1,2,3-triazole-4-carboxamide (4c).
Yield: 78%;
white flaky crystals; mp 105–107ꢀC; [a]D17.0 = À48.696
(c= 11.5mg/mL, CHCl3); 1HNMR (d ppm, CDCl3): 2.464
(s, 3H), 2.975–3.067 (dd, 2H, J = 1.6, 7.6 Hz; b, 1H, -OH),
3.694–3.722(dd, 1H, J = 5.6, 11.2 Hz), 3.795–3.822(dd, 1H,
J = 3.6, 11.2 Hz), 4.369–4.448(m, 1H), 7.209–7.266(m, 1H, N-
H), 7.307–7.339(m, 4H), 7.398–7.417(dd, 2H, J = 1.2, 7.6 Hz),
7.464–7.502(t, 1H, J = 7.8 Hz), 7.533–7.587(m, 2H), 7.612–7.632
(d, 1H, J= 8.0 Hz, CO-NH); 13CHNR (d ppm, CDCl3): 9.29,
37.49, 53.14, 64.41, 126.83, 128.22, 128.85, 129.35, 129.50,
130.88, 131.98, 132.26, 133.31, 137.83, 137.99, 138.84, 161.88;
MS M/z (%): 370 (M+, 0.31) 372 (M + 2, 0.1), 355(0.5), 341(1),
339(2), 281(3), 279(10), 259 (3), 241(4), 223(6), 205(6), 195
(5), 178(16), 168(7), 165(7), 149(88), 147(11), 141(10), 129
(40), 113(13), 112(17), 111(20), 105(10), 97(19), 91(11), 85(24),
83(37), 71(40), 57(100), 43(58). IR(KBr, cm-1): 500.3, 530.4,
X-ray structure determination of 4e. Colorless Block,
C19H19ClN4O2, Mr = 370.83, CCDC 800563, Monoclinic, space
group P2(1), a = 13.029 (7), b = 7.727(4), c = 18.954(10) Å,
a = 90.00, b = 105.582(8), g = 90.00 º, V = 1838.0(17) Å3, Z = 4,
Dx = 1.340 Mg mÀ3, F000 = 776, m = 0.229 mmÀ1. Intensity data
were collected using a Siemens SMART diffractometer at 296(2)
K, graphite monochromator MoKa radiation (l = 0.071073 nm),
using the o-2θ scan technique to a maximum of 0.981 ~ 25.50º.
A total of 11896 reflections were collected with 8304 unique
ones (R = 0.0339), of which 3133 reflections were observed with
I >2s(I). The final int R and wR values were 0.0536 and 0.1488,
s = 0.978, (Δ/s) max = 0.000. Flack = 0.06(9). The maximum
peak and minimum peak in the final difference map is 0.428
and À0.194 e ÅÀ3
.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2013
(S)-N-(-1-hydroxy-3- phenylpropan-2-yl)-1,2,3- triazole carboxamide
(S)-N-(1-Hydroxy-3-phenylpropan-2-yl)-5-methyl-1-(4-
methylphenyl)-1 H-1,2,3-triazole-4-carboxamide (4f). Yield:
3090.4, 3109.4, 3195.6, 3377.5. Anal. Calcd. for C19H19N5O4:
C, 59.84; H, 5.02; N, 18.36; Found: C, 59.96; H, 5.12; N, 18.20.
(S)-N-(1-Hydroxy-3-phenylpropan-2-yl)-5-methyl-1-(naphthalen-
97%; white flaky crystals; mp 136–138ꢀC; [a]D17.2 = À29.293
(c= 9.9 mg/mL, CHCl3); 1 H NMR d(ppm, CDCl3): 2.449 (s, 3H),
2.560 (s, 3H), 2.991–3.017(dd, 2H, J = 3.2, 6.8 Hz), 3.158(s,1H,
OH), 3.679–3.721(dd, 1H, J = 5.6, 11.2 Hz), 3.782–3.819(dd,
1H, 1J = 4.0, 11.2 Hz), 4.365–4.463(m, 1H), 7.132–7.152 (m, 1H,
J = 4.0 Hz), 7.186–7.357(m, 8H), 7.568–7.588(d, 1H, J = 8.0
Hz, CO-NH); 13CHNR (d ppm, CDCl3): 9.89, 21.43, 37.48,
53.10, 64.42, 125.24, 126.76, 128.79, 129.49, 130.36, 133.20,
137.05, 137.90, 138.37, 140.45, 162.06; MS M/z (%): 350
(M+, 0.24) 341(1), 319(2), 309(1), 289(2), 279(3), 259(17), 241
(6), 223(7), 205(9), 200(4), 178(4), 165(4), 149(100), 147
(15), 129(34), 128(10), 113(11), 112(16), 111(18), 105(8), 97
(14), 83(25), 70(27), 57(38), 43(60). IR(KBr, cm-1):
512.4, 546.2, 625.4, 698.7, 746.1, 822.2, 1041.0, 1062.8,
1088.2, 1115.8, 1138.8, 1277.3, 1450.9, 1469.9, 1512.8,
1577.9, 1594.6, 1647.3, 2919.9, 2950.1, 3024.0, 3081.0,
3371.5, 3400.5. Anal. Calcd. for C20H22N4O2: C, 68.55;
H, 6.33; N, 15.99; Found: C, 68.64; H, 6.43; N, 15.89.
2-yl)-1 H-1,2,3-triazole-4-carboxamide (4i).
Yield: 95%; white
needle crystals; mp 178–179ꢀC; [a]D17.6 = À43.564 (c = 10.1 mg/
mL, CHCl3); 1H NMR d(ppm, CDCl3): 2.647(s, 3H), 3.019–
3.043(dd, 2 H, J = 1.2, 7.6 Hz; b, 1 H, -OH); 3.705–3.747(dd, 1 H,
J = 5.6, 11.2 Hz), 3.812–3.849(dd,1H, J = 3.6, 11.2 Hz), 4.384–
4.462(m, 1H), 7.202–7.245(m, 1H), 7.285–7.317(m, 4H, J = Hz),
7.493–7.519(q, 1H, J = 2.0, 8.4 Hz), 7.493–7.519(m, 4H), 7.584–
7.636(m, 3H), 7.903–7.954(m, 3H), 8.003–8.025(d, 1H, J = 8.8
Hz, CO-NH); 13CHNR (d ppm, CDCl3): 10.07, 37.53, 53.17,
64.48, 122.73, 124.48, 126.82, 127.73, 127.92, 128.16, 128.58,
128.84, 129.52, 130.06, 133.04, 133.12, 133.53, 137.28, 137.90,
138.57, 162.02; MS M/z (%): 386 (M+, 0.40) 368(0.51), 350
(0.53), 349(1.3), 290(3), 289(16), 274(1), 268(2), 250(2), 231
(5), 224(5), 210(7), 202(7), 174(7), 150(3), 149(19), 146(8), 129
(11), 127(4), 120(7), 113(5), 112(7), 111(11), 105(11), 97(14), 91
(13), 83(15), 69(18), 57(28), 45(47), 44(100), 43(59). IR(KBr,
cm-1): 477.4, 701.3, 749.3, 817.9, 867.0, 1050.7, 1086.4, 1269.9,
1425.6, 1450.3, 1461.3, 1509.5, 1585.8, 1653.6, 2924.5, 2943.7,
2981.2, 3002.1, 3030.1, 3052.3, 3403.7, 3456.8. Anal. Calcd. for
C23H22N4O2: C, 71.48; H, 5.74; N, 14.50; Found: C, 71.56; H,
5.65; N, 14.36.
(S)-1-(4-Ethoxyphenyl)-N-(1-hydroxy-3-phenylpropan-2-yl)-
5-methyl-1 H-1,2,3-triazole-4-carboxamide (4g).
Yield: 65%;
white flaky crystals; mp 104–107ꢀC; [a]D17.6 =À49.153
1
(c = 11.8 mg/mL, CHCl3); H NMR d(ppm, CDCl3): 1.442–1.477
(t, 3H, J = 7.0 Hz), 2.544 (s, 3H), 2.957–3.052(dd, 2H,
J = 3.4, 7.4 Hz; b, 1H, OH), 3.680–3.721(dd, 1H, J = 5.2, 11.2
Hz), 3.785–3.822(dd, 1H, J = 3.6, 11.2 Hz), 4.070–4.122(q,
2H, J = 7.0 Hz), 4.355–4.414(m, 1H), 7.013–7.035(d, 2H,
J = 8.8 Hz), 7.193–7.247(m, 1H), 7.292–7.322(m, 6H), 7.532–
7.552(d, 1H, J = 8.0 Hz, CO-NH); 13CHNR(d ppm, CDCl3):
9.86, 14.88, 37.51, 53.12, 64.17, 64.48, 115.41, 126.79, 126.83,
128.33, 128.82, 129.50, 137.18, 137.90, 138.28, 160.24, 162.08;
MS M/z (%): 380 (M+, 0.35) 350(3), 349(10), 323(1), 290(16),
289(100), 271(3), 247(4), 230(17), 203(5), 202(30), 175(7),
174(22), 162(8), 149(15), 146(20), 117(4), 111(2), 105(3), 91
(13), 83(3), 77(3), 65(5), 57(5), 43(6), 40(30); IR(KBr, cm-1):
527.8, 655.1, 701.4, 745.3, 833.7, 865.9, 918.8, 1038.6, 1085.3,
1114.5, 1141.3, 1247.4, 1390.6, 1471.9, 1513.6, 1594.3, 1630.3,
1652.2, 2931.1, 2977.9, 3025.9, 3056.3, 3200.7, 3396.3. Anal.
Calcd. for C21H24N4O3: C, 66.30; H, 6.36; N, 14.73; Found: C,
66.36; H, 6.29; N, 17.65.
(S)-1-(4-Chlorophenyl)-N-(1-hydroxy-3-phenylpropan-2-
yl)-5-methoxy-1 H-1,2,3-triazole-4-carboxamide (4j).
Yield:
68%; white flaky crystals; mp 179–181ꢀC; [a]D17.2 = À129.66
1
(c= 11.8mg/mL, CHCl3); H NMR d(ppm, CDCl3): 2.782(s, 1H,
-OH), 2.896–3.016(ddd, 2H), 3.638–3.679(dd, 1H, J = 5.4, 11.0
Hz), 3.745–3.779(dd, 1 H, J = 2.6, 11.0 Hz), 4.270–4.642
(m,1H; s, 3H, -OCH3), 7.187–7.242(m, 1H), 7.268–7.314(m, 4H),
7.448–7.484(m, 2 H, J = 2.0, 7.2 Hz), 7.954–7.976(dd, 2H, J = 2.0,
7.2 Hz), 8.574–8.594(d, 1 H, J = 8.0 Hz, -CO-NH-); 13CHNR
(d ppm): 37.69, 41.33, 53.20, 64.80, 112.52, 122.19, 126.79,
128.77, 129.51, 129.71, 133.92, 134.35, 137.92, 156.61, 158.81;
MS M/z (%): 386 (M+, 2.08) 388(M + 2, 0.5), 368(1.2), 355(4),
341(1), 307(6), 297(14), 295(24), 283(4), 277(3), 256(6),
238(14), 236(41), 223(9), 205(8), 198(12), 196(8), 169(6), 157
(15), 149(100), 129(14), 121(9), 111(24), 105(11), 97(19), 91(18),
83(22), 69(25), 57(38), 45(54), 44(68), 43(61). IR(KBr, cm-1):
505.6, 526.4, 595.3, 627.8, 701.5, 751.1, 830.9, 868.0,
1010.9, 1034.9, 1083.1, 1184.1, 1259.6, 1304.7, 1415.9, 1449.2,
1491.1, 1541.8, 1632.7, 1679.9, 2936.6, 2958.0, 3025.7,
3056.0, 3079.2, 3102.5, 3290.1, 3474.7. Anal. Calcd. for
C19H19ClN4O3: C, 58.99; H, 4.95; N, 14.48; Found: C, 58.86; H,
5.04; N, 14.31.
(S)-N-(1-Hydroxy-3-phenylpropan-2-yl)-5-methyl-1-(3-
nitrophenyl)-1H-1,2,3-triazole-4-carboxamide (4h).
Yield:
96%; white needle crystals; mp 179–182ꢀC; [a]
17.7 = À11.382 (c = 6.15 mg/mL, CHCl3); 1HNMR (d ppm,
D
DMSO-d6): 2.541(s, 3 H), 2.854–2.910(dd, 1H, J = 8.8, 13.6
Hz), 2.958–3.006(dd, 1H, J = 5.6, 13.6 Hz), 3.436-3.556(m,
2H), 4.199–4.284(m, 1H), 4.937–4.965(t, 1H, J = 5.6 Hz,
OH), 7.154–7.196(m, 1H), 7.274–7.287(m, 4H), 7.920–7.961
(t, 1H, J = 8.2 Hz), 8.123–8.144(d, 1H, J = 8.4 Hz), 8.298–
8.321(d, 1H, J = 9.2 Hz, CON-H), 8.456–8.476(d, 1H, J = 8.0
Hz, CO-NH), 8.505–8.515(t, 1H, J = 2.0 Hz); 13CHNR (d
ppm, DMSO-d6): 10.34; 37.51; 53.26; 63.74; 121.63;
125.77; 127.03; 129.28; 130.18; 132.37; 132.89; 137.18;
138.39; 139.35; 140.41; 149.39; 161.28; MS M/z (%): 381
(M+, 0.16) 369(0.12), 355(0.31), 343(0.23), 325(0.62), 295(1),
290(3), 241(2), 223(8), 205(5), 150(9), 149(100), 147(4), 129
(9), 121(4), 113(2), 112(4), 111(4), 105(4), 97(3), 83(4), 70
(7), 57(11), 43(25), 40(45). IR(KBr, cm-1): 553.1, 602.6, 620.3,
674.2, 704.1, 753.1, 875.5, 897.7, 1045.4, 1100.2, 1149.5,
1266.3, 1288.0, 1349.5, 1420.9, 1452.8, 1493.4, 1536.8,
1586.1, 1664.3, 2867.0, 2918.6, 2944.9, 3024.6, 3057.6,
Acknowledgment. The authors wish to acknowledge the
supported by Lanzhou University SKLAOC.
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